Torsade B-Disease 0
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. O 0

The O 0
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This O 0
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hypothesis O 0
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The O 0
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Positive O 0
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. O 0

In O 0
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contrast B-Chemical 0
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) O 0
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The O 0
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After O 0
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) O 0
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delayed O 0
macro B-Disease 0
- I-Disease 0
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appeared O 0
, O 0
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n O 0
degree O 0
2 O 0
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pain B-Disease 0
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The O 0
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Risk O 0
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From O 0
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were O 0
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None O 0
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. O 0

Onset O 0
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0 O 0
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Among O 0
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14 O 0
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Higher O 0
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In O 0
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In O 0
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3 O 0
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These O 0
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It O 0
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Nociceptin B-Chemical 0
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On O 0
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nociceptin B-Chemical 0
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. O 0

2 O 0
. O 0

Although O 0
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3 O 0
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The O 0
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nociceptin B-Chemical 0
/ O 0
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could O 0
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impairment B-Disease 0
of I-Disease 0
learning I-Disease 0
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4 O 0
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While O 0
nocistatin B-Chemical 0
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, O 0
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shorter O 0
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nociceptin B-Chemical 0
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Administration O 0
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attenuated O 0
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scopolamine B-Chemical 0
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spontaneous O 0
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. O 0

6 O 0
. O 0

These O 0
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indicated O 0
that O 0
nocistatin B-Chemical 0
, O 0
a O 0
new O 0
biologically O 0
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peptide O 0
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ameliorates O 0
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scopolamine B-Chemical 0
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that O 0
these O 0
peptides O 0
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opposite O 0
roles O 0
in O 0
learning O 0
and O 0
memory O 0
. O 0

Meloxicam B-Chemical 0
- O 0
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liver B-Disease 0
toxicity I-Disease 0
. O 0

We O 0
report O 0
the O 0
case O 0
of O 0
a O 0
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patient O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
who O 0
developed O 0
acute O 0
cytolytic O 0
hepatitis B-Disease 0
due O 0
to O 0
meloxicam B-Chemical 0
. O 0

Recently O 0
introduced O 0
in O 0
Belgium O 0
, O 0
meloxicam B-Chemical 0
is O 0
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nonsteroidal O 0
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. O 0

The O 0
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occurred O 0
rapidly O 0
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meloxicam B-Chemical 0
administration O 0
and O 0
was O 0
associated O 0
with O 0
the O 0
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of O 0
antinuclear O 0
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suggesting O 0
a O 0
hypersensitivity B-Disease 0
mechanism O 0
. O 0

This O 0
first O 0
case O 0
of O 0
meloxicam B-Chemical 0
related O 0
liver B-Disease 0
toxicity I-Disease 0
demonstrates O 0
the O 0
potential O 0
of O 0
this O 0
drug O 0
to O 0
induce O 0
hepatic B-Disease 0
damage I-Disease 0
. O 0

Induction O 0
of O 0
apoptosis O 0
by O 0
remoxipride B-Chemical 0
metabolites O 0
in O 0
HL60 O 0
and O 0
CD34 O 0
+ O 0
/ O 0
CD19 O 0
- O 0
human O 0
bone O 0
marrow O 0
progenitor O 0
cells O 0
: O 0
potential O 0
relevance O 0
to O 0
remoxipride B-Chemical 0
- O 0
induced O 0
aplastic B-Disease 0
anemia I-Disease 0
. O 0

The O 0
antipsychotic O 0
agent O 0
, O 0
remoxipride B-Chemical 0
[ O 0
( B-Chemical 0
S I-Chemical 0
) I-Chemical 0
- I-Chemical 0
( I-Chemical 0
- I-Chemical 0
) I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
bromo I-Chemical 0
- I-Chemical 0
N I-Chemical 0
- I-Chemical 0
[ I-Chemical 0
( I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
ethyl I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
pyrrolidinyl I-Chemical 0
) I-Chemical 0
methyl I-Chemical 0
] I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
, I-Chemical 0
6 I-Chemical 0
- I-Chemical 0
dimethoxybenz I-Chemical 0
amide I-Chemical 0
] O 0
has O 0
been O 0
associated O 0
with O 0
acquired O 0
aplastic B-Disease 0
anemia I-Disease 0
. O 0

We O 0
have O 0
examined O 0
the O 0
ability O 0
of O 0
remoxipride B-Chemical 0
, O 0
three O 0
pyrrolidine B-Chemical 0
ring O 0
metabolites O 0
and O 0
five O 0
aromatic O 0
ring O 0
metabolites O 0
of O 0
the O 0
parent O 0
compound O 0
to O 0
induce O 0
apoptosis O 0
in O 0
HL60 O 0
cells O 0
and O 0
human O 0
bone O 0
marrow O 0
progenitor O 0
( O 0
HBMP O 0
) O 0
cells O 0
. O 0

Cells O 0
were O 0
treated O 0
for O 0
0 O 0
- O 0
24 O 0
h O 0
with O 0
each O 0
compound O 0
( O 0
0 O 0
- O 0
200 O 0
microM O 0
) O 0
. O 0

Apoptosis O 0
was O 0
assessed O 0
by O 0
fluorescence O 0
microscopy O 0
in O 0
Hoechst B-Chemical 0
33342 I-Chemical 0
- O 0
and O 0
propidium B-Chemical 0
iodide I-Chemical 0
stained O 0
cell O 0
samples O 0
. O 0

Results O 0
were O 0
confirmed O 0
by O 0
determination O 0
of O 0
internucleosomal O 0
DNA O 0
fragmentation O 0
using O 0
gel O 0
electrophoresis O 0
for O 0
HL60 O 0
cell O 0
samples O 0
and O 0
terminal O 0
deoxynucleotidyl O 0
transferase O 0
assay O 0
in O 0
HBMP O 0
cells O 0
. O 0

The O 0
catechol B-Chemical 0
and O 0
hydroquinone B-Chemical 0
metabolites O 0
, O 0
NCQ436 B-Chemical 0
and O 0
NCQ344 B-Chemical 0
, O 0
induced O 0
apoptosis O 0
in O 0
HL60 O 0
and O 0
HBMP O 0
cells O 0
in O 0
a O 0
time O 0
- O 0
and O 0
concentration O 0
dependent O 0
manner O 0
, O 0
while O 0
the O 0
phenols B-Chemical 0
, O 0
NCR181 O 0
, O 0
FLA873 O 0
, O 0
and O 0
FLA797 B-Chemical 0
, O 0
and O 0
the O 0
derivatives O 0
formed O 0
by O 0
oxidation O 0
of O 0
the O 0
pyrrolidine B-Chemical 0
ring O 0
, O 0
FLA838 O 0
, O 0
NCM001 O 0
, O 0
and O 0
NCL118 O 0
, O 0
had O 0
no O 0
effect O 0
. O 0

No O 0
necrosis B-Disease 0
was O 0
observed O 0
in O 0
cells O 0
treated O 0
with O 0
NCQ436 B-Chemical 0
but O 0
NCQ344 B-Chemical 0
had O 0
a O 0
biphasic O 0
effect O 0
in O 0
both O 0
cell O 0
types O 0
, O 0
inducing O 0
apoptosis O 0
at O 0
lower O 0
concentrations O 0
and O 0
necrosis B-Disease 0
at O 0
higher O 0
concentrations O 0
. O 0

These O 0
data O 0
show O 0
that O 0
the O 0
catechol B-Chemical 0
and O 0
hydroquinone B-Chemical 0
metabolites O 0
of O 0
remoxipride B-Chemical 0
have O 0
direct O 0
toxic O 0
effects O 0
in O 0
HL60 O 0
and O 0
HBMP O 0
cells O 0
, O 0
leading O 0
to O 0
apoptosis O 0
, O 0
while O 0
the O 0
phenol B-Chemical 0
metabolites O 0
were O 0
inactive O 0
. O 0

Similarly O 0
, O 0
benzene B-Chemical 0
- O 0
derived O 0
catechol B-Chemical 0
and O 0
hydroquinone B-Chemical 0
, O 0
but O 0
not O 0
phenol B-Chemical 0
, O 0
induce O 0
apoptosis O 0
in O 0
HBMP O 0
cells O 0
[ O 0
Moran O 0
et O 0
al O 0
. O 0
, O 0
Mol O 0
. O 0
Pharmacol O 0
. O 0
, O 0
50 O 0
( O 0
1996 O 0
) O 0
610 O 0
- O 0
615 O 0
] O 0
. O 0

We O 0
propose O 0
that O 0
remoxipride B-Chemical 0
and O 0
benzene B-Chemical 0
may O 0
induce O 0
aplastic B-Disease 0
anemia I-Disease 0
via O 0
production O 0
of O 0
similar O 0
reactive O 0
metabolites O 0
and O 0
that O 0
the O 0
ability O 0
of O 0
NCQ436 B-Chemical 0
and O 0
NCQ344 B-Chemical 0
to O 0
induce O 0
apoptosis O 0
in O 0
HBMP O 0
cells O 0
may O 0
contribute O 0
to O 0
the O 0
mechanism O 0
underlying O 0
acquired O 0
aplastic B-Disease 0
anemia I-Disease 0
that O 0
has O 0
been O 0
associated O 0
with O 0
remoxipride B-Chemical 0
. O 0

Synthesis O 0
and O 0
preliminary O 0
pharmacological O 0
investigations O 0
of O 0
1 B-Chemical 0
- I-Chemical 0
( I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
dihydro I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
acenaphthylenyl I-Chemical 0
) I-Chemical 0
piperazine I-Chemical 0
derivatives O 0
as O 0
potential O 0
atypical O 0
antipsychotic O 0
agents O 0
in O 0
mice O 0
. O 0

In O 0
research O 0
towards O 0
the O 0
development O 0
of O 0
new O 0
atypical O 0
antipsychotic O 0
agents O 0
, O 0
one O 0
strategy O 0
is O 0
that O 0
the O 0
dopaminergic O 0
system O 0
can O 0
be O 0
modulated O 0
through O 0
manipulation O 0
of O 0
the O 0
serotonergic O 0
system O 0
. O 0

The O 0
synthesis O 0
and O 0
preliminary O 0
pharmacological O 0
evaluation O 0
of O 0
a O 0
series O 0
of O 0
potential O 0
atypical O 0
antipsychotic O 0
agents O 0
based O 0
on O 0
the O 0
structure O 0
of O 0
1 B-Chemical 0
- I-Chemical 0
( I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
dihydro I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
acenaphthylenyl I-Chemical 0
) I-Chemical 0
piperazine I-Chemical 0
( O 0
7 O 0
) O 0
is O 0
described O 0
. O 0

Compound O 0
7e O 0
, O 0
5 B-Chemical 0
- I-Chemical 0
{ I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
[ I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
( I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
dihydro I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
acenaphthylenyl I-Chemical 0
) I-Chemical 0
piperazinyl I-Chemical 0
] I-Chemical 0
ethyl I-Chemical 0
} I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
, I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
dihy I-Chemical 0
dro I-Chemical 0
- I-Chemical 0
1H I-Chemical 0
- I-Chemical 0
indol I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
one I-Chemical 0
, O 0
from O 0
this O 0
series O 0
showed O 0
significant O 0
affinities O 0
at O 0
the O 0
5 O 0
- O 0
HT1A O 0
and O 0
5 O 0
- O 0
HT2A O 0
receptors O 0
and O 0
moderate O 0
affinity O 0
at O 0
the O 0
D2 O 0
receptor O 0
. O 0

7e O 0
exhibits O 0
a O 0
high O 0
reversal O 0
of O 0
catalepsy B-Disease 0
induced O 0
by O 0
haloperidol B-Chemical 0
indicating O 0
its O 0
atypical O 0
antipsychotic O 0
nature O 0
. O 0

Sub O 0
- O 0
chronic O 0
inhibition O 0
of O 0
nitric B-Chemical 0
- I-Chemical 0
oxide I-Chemical 0
synthesis O 0
modifies O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
and O 0
the O 0
number O 0
of O 0
NADPH B-Chemical 0
- O 0
diaphorase O 0
neurons O 0
in O 0
mice O 0
. O 0

RATIONALE O 0
: O 0
NG B-Chemical 0
- I-Chemical 0
nitro I-Chemical 0
- I-Chemical 0
L I-Chemical 0
- I-Chemical 0
arginine I-Chemical 0
( O 0
L B-Chemical 0
- I-Chemical 0
NOARG I-Chemical 0
) O 0
, O 0
an O 0
inhibitor O 0
of O 0
nitric B-Chemical 0
- I-Chemical 0
oxide I-Chemical 0
synthase O 0
( O 0
NOS O 0
) O 0
, O 0
induces O 0
catalepsy B-Disease 0
in O 0
mice O 0
. O 0

This O 0
effect O 0
undergoes O 0
rapid O 0
tolerance O 0
, O 0
showing O 0
a O 0
significant O 0
decrease O 0
after O 0
2 O 0
days O 0
of O 0
sub O 0
- O 0
chronic O 0
L B-Chemical 0
- I-Chemical 0
NOARG I-Chemical 0
treatment O 0
. O 0

Nitric B-Chemical 0
oxide I-Chemical 0
( O 0
NO B-Chemical 0
) O 0
has O 0
been O 0
shown O 0
to O 0
influence O 0
dopaminergic O 0
neurotransmission O 0
in O 0
the O 0
striatum O 0
. O 0

Neuroleptic O 0
drugs O 0
such O 0
as O 0
haloperidol B-Chemical 0
, O 0
which O 0
block O 0
dopamine B-Chemical 0
receptors O 0
, O 0
also O 0
cause O 0
catalepsy B-Disease 0
in O 0
rodents O 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
investigate O 0
the O 0
effects O 0
of O 0
subchronic O 0
L B-Chemical 0
- I-Chemical 0
NOARG I-Chemical 0
treatment O 0
in O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
and O 0
the O 0
number O 0
of O 0
NOS O 0
neurons O 0
in O 0
areas O 0
related O 0
to O 0
motor O 0
control O 0
. O 0

METHODS O 0
: O 0
Male O 0
albino O 0
Swiss O 0
mice O 0
were O 0
treated O 0
sub O 0
- O 0
chronically O 0
( O 0
twice O 0
a O 0
day O 0
for O 0
4 O 0
days O 0
) O 0
with O 0
L B-Chemical 0
- I-Chemical 0
NOARG I-Chemical 0
( O 0
40 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
or O 0
haloperidol B-Chemical 0
( O 0
1 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

Catalepsy B-Disease 0
was O 0
evaluated O 0
at O 0
the O 0
beginning O 0
and O 0
the O 0
end O 0
of O 0
the O 0
treatments O 0
. O 0

Reduced O 0
nicotinamide B-Chemical 0
adenine I-Chemical 0
dinucleotide I-Chemical 0
phosphate I-Chemical 0
- O 0
diaphorase O 0
( O 0
NADPH B-Chemical 0
- O 0
d O 0
) O 0
histochemistry O 0
was O 0
also O 0
employed O 0
to O 0
visualize O 0
NOS O 0
as O 0
an O 0
index O 0
of O 0
enzyme O 0
expression O 0
in O 0
mice O 0
brain O 0
regions O 0
related O 0
to O 0
motor O 0
control O 0
. O 0

RESULTS O 0
: O 0
L B-Chemical 0
- I-Chemical 0
NOARG I-Chemical 0
sub O 0
- O 0
chronic O 0
administration O 0
produced O 0
tolerance O 0
of O 0
L B-Chemical 0
- I-Chemical 0
NOARG I-Chemical 0
and O 0
of O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
. O 0

It O 0
also O 0
induced O 0
an O 0
increase O 0
in O 0
the O 0
number O 0
of O 0
NADPH B-Chemical 0
- O 0
d O 0
- O 0
positive O 0
cells O 0
in O 0
the O 0
dorsal O 0
part O 0
of O 0
the O 0
caudate O 0
and O 0
accumbens O 0
nuclei O 0
compared O 0
with O 0
haloperidol B-Chemical 0
and O 0
in O 0
the O 0
pedunculopontine O 0
tegmental O 0
nucleus O 0
compared O 0
with O 0
saline O 0
. O 0

In O 0
contrast O 0
, O 0
there O 0
was O 0
a O 0
decrease O 0
in O 0
NADPH B-Chemical 0
- O 0
d O 0
neuron O 0
number O 0
in O 0
the O 0
substantia O 0
nigra O 0
, O 0
pars O 0
compacta O 0
in O 0
both O 0
haloperidol B-Chemical 0
- O 0
treated O 0
and O 0
L B-Chemical 0
- I-Chemical 0
NOARG I-Chemical 0
- O 0
treated O 0
animals O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
results O 0
give O 0
further O 0
support O 0
to O 0
the O 0
hypothesis O 0
that O 0
NO B-Chemical 0
plays O 0
a O 0
role O 0
in O 0
motor O 0
behavior O 0
control O 0
and O 0
suggest O 0
that O 0
it O 0
may O 0
take O 0
part O 0
in O 0
the O 0
synaptic O 0
changes O 0
produced O 0
by O 0
antipsychotic O 0
treatment O 0
. O 0

Prolonged O 0
left B-Disease 0
ventricular I-Disease 0
dysfunction I-Disease 0
occurs O 0
in O 0
patients O 0
with O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
after O 0
both O 0
dobutamine B-Chemical 0
and O 0
exercise O 0
induced O 0
myocardial B-Disease 0
ischaemia I-Disease 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
determine O 0
whether O 0
pharmacological O 0
stress O 0
leads O 0
to O 0
prolonged O 0
but O 0
reversible O 0
left B-Disease 0
ventricular I-Disease 0
dysfunction I-Disease 0
in O 0
patients O 0
with O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
, O 0
similar O 0
to O 0
that O 0
seen O 0
after O 0
exercise O 0
. O 0

DESIGN O 0
: O 0
A O 0
randomised O 0
crossover O 0
study O 0
of O 0
recovery O 0
time O 0
of O 0
systolic O 0
and O 0
diastolic O 0
left O 0
ventricular O 0
function O 0
after O 0
exercise O 0
and O 0
dobutamine B-Chemical 0
induced O 0
ischaemia B-Disease 0
. O 0

SUBJECTS O 0
: O 0
10 O 0
patients O 0
with O 0
stable B-Disease 0
angina I-Disease 0
, O 0
angiographically O 0
proven O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
, O 0
and O 0
normal O 0
left O 0
ventricular O 0
function O 0
. O 0

INTERVENTIONS O 0
: O 0
Treadmill O 0
exercise O 0
and O 0
dobutamine B-Chemical 0
stress O 0
were O 0
performed O 0
on O 0
different O 0
days O 0
. O 0

Quantitative O 0
assessment O 0
of O 0
systolic O 0
and O 0
diastolic O 0
left O 0
ventricular O 0
function O 0
was O 0
performed O 0
using O 0
transthoracic O 0
echocardiography O 0
at O 0
baseline O 0
and O 0
at O 0
regular O 0
intervals O 0
after O 0
each O 0
test O 0
. O 0

RESULTS O 0
: O 0
Both O 0
forms O 0
of O 0
stress O 0
led O 0
to O 0
prolonged O 0
but O 0
reversible O 0
systolic O 0
and O 0
diastolic O 0
dysfunction O 0
. O 0

There O 0
was O 0
no O 0
difference O 0
in O 0
the O 0
maximum O 0
double O 0
product O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
53 O 0
) O 0
or O 0
ST O 0
depression B-Disease 0
( O 0
p O 0
= O 0
0 O 0
. O 0
63 O 0
) O 0
with O 0
either O 0
form O 0
of O 0
stress O 0
. O 0

After O 0
exercise O 0
, O 0
ejection O 0
fraction O 0
was O 0
reduced O 0
at O 0
15 O 0
and O 0
30 O 0
minutes O 0
compared O 0
with O 0
baseline O 0
( O 0
mean O 0
( O 0
SEM O 0
) O 0
, O 0
- O 0
5 O 0
. O 0
6 O 0
( O 0
1 O 0
. O 0
5 O 0
) O 0
% O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
; O 0
and O 0
- O 0
6 O 0
. O 0
1 O 0
( O 0
2 O 0
. O 0
2 O 0
) O 0
% O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
, O 0
and O 0
at O 0
30 O 0
and O 0
45 O 0
minutes O 0
after O 0
dobutamine B-Chemical 0
( O 0
- O 0
10 O 0
. O 0
8 O 0
( O 0
1 O 0
. O 0
8 O 0
) O 0
% O 0
and O 0
- O 0
5 O 0
. O 0
5 O 0
( O 0
1 O 0
. O 0
8 O 0
) O 0
% O 0
, O 0
both O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Regional O 0
analysis O 0
showed O 0
a O 0
reduction O 0
in O 0
the O 0
worst O 0
affected O 0
segment O 0
15 O 0
and O 0
30 O 0
minutes O 0
after O 0
exercise O 0
( O 0
- O 0
27 O 0
. O 0
9 O 0
( O 0
7 O 0
. O 0
2 O 0
) O 0
% O 0
and O 0
- O 0
28 O 0
. O 0
6 O 0
( O 0
5 O 0
. O 0
7 O 0
) O 0
% O 0
, O 0
both O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
, O 0
and O 0
at O 0
30 O 0
minutes O 0
after O 0
dobutamine B-Chemical 0
( O 0
- O 0
32 O 0
( O 0
5 O 0
. O 0
3 O 0
) O 0
% O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

The O 0
isovolumic O 0
relaxation O 0
period O 0
was O 0
prolonged O 0
45 O 0
minutes O 0
after O 0
each O 0
form O 0
of O 0
stress O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
patients O 0
with O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
, O 0
dobutamine B-Chemical 0
induced O 0
ischaemia B-Disease 0
results O 0
in O 0
prolonged O 0
reversible O 0
left B-Disease 0
ventricular I-Disease 0
dysfunction I-Disease 0
, O 0
presumed O 0
to O 0
be O 0
myocardial B-Disease 0
stunning I-Disease 0
, O 0
similar O 0
to O 0
that O 0
seen O 0
after O 0
exercise O 0
. O 0

Dobutamine B-Chemical 0
induced O 0
ischaemia B-Disease 0
could O 0
therefore O 0
be O 0
used O 0
to O 0
study O 0
the O 0
pathophysiology O 0
of O 0
this O 0
phenomenon O 0
further O 0
in O 0
patients O 0
with O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
. O 0

Anorexigens O 0
and O 0
pulmonary B-Disease 0
hypertension I-Disease 0
in O 0
the O 0
United O 0
States O 0
: O 0
results O 0
from O 0
the O 0
surveillance O 0
of O 0
North O 0
American O 0
pulmonary B-Disease 0
hypertension I-Disease 0
. O 0

BACKGROUND O 0
: O 0
The O 0
use O 0
of O 0
appetite O 0
suppressants O 0
in O 0
Europe O 0
has O 0
been O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
primary B-Disease 0
pulmonary I-Disease 0
hypertension I-Disease 0
( O 0
PPH B-Disease 0
) O 0
. O 0

Recently O 0
, O 0
fenfluramine B-Chemical 0
appetite O 0
suppressants O 0
became O 0
widely O 0
used O 0
in O 0
the O 0
United O 0
States O 0
but O 0
were O 0
withdrawn O 0
in O 0
September O 0
1997 O 0
because O 0
of O 0
concerns O 0
over O 0
adverse O 0
effects O 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
We O 0
conducted O 0
a O 0
prospective O 0
surveillance O 0
study O 0
on O 0
patients O 0
diagnosed O 0
with O 0
pulmonary B-Disease 0
hypertension I-Disease 0
at O 0
12 O 0
large O 0
referral O 0
centers O 0
in O 0
North O 0
America O 0
. O 0

Data O 0
collected O 0
on O 0
patients O 0
seen O 0
from O 0
September O 0
1 O 0
, O 0
1996 O 0
, O 0
to O 0
December O 0
31 O 0
, O 0
1997 O 0
, O 0
included O 0
the O 0
cause O 0
of O 0
the O 0
pulmonary B-Disease 0
hypertension I-Disease 0
and O 0
its O 0
severity O 0
. O 0

Patients O 0
with O 0
no O 0
identifiable O 0
cause O 0
of O 0
pulmonary B-Disease 0
hypertension I-Disease 0
were O 0
classed O 0
as O 0
PPH B-Disease 0
. O 0

A O 0
history O 0
of O 0
drug O 0
exposure O 0
also O 0
was O 0
taken O 0
with O 0
special O 0
attention O 0
on O 0
the O 0
use O 0
of O 0
antidepressants O 0
, O 0
anorexigens O 0
, O 0
and O 0
amphetamines B-Chemical 0
. O 0

RESULTS O 0
: O 0
Five O 0
hundred O 0
seventy O 0
- O 0
nine O 0
patients O 0
were O 0
studied O 0
, O 0
205 O 0
with O 0
PPH B-Disease 0
and O 0
374 O 0
with O 0
pulmonary B-Disease 0
hypertension I-Disease 0
from O 0
other O 0
causes O 0
( O 0
secondary O 0
pulmonary B-Disease 0
hypertension I-Disease 0
[ O 0
SPH O 0
] O 0
) O 0
. O 0

The O 0
use O 0
of O 0
anorexigens O 0
was O 0
common O 0
in O 0
both O 0
groups O 0
. O 0

However O 0
, O 0
of O 0
the O 0
medications O 0
surveyed O 0
, O 0
only O 0
the O 0
fenfluramines B-Chemical 0
had O 0
a O 0
significant O 0
preferential O 0
association O 0
with O 0
PPH B-Disease 0
as O 0
compared O 0
with O 0
SPH O 0
( O 0
adjusted O 0
odds O 0
ratio O 0
for O 0
use O 0
> O 0
6 O 0
months O 0
, O 0
7 O 0
. O 0
5 O 0
; O 0
95 O 0
% O 0
confidence O 0
interval O 0
, O 0
1 O 0
. O 0
7 O 0
to O 0
32 O 0
. O 0
4 O 0
) O 0
. O 0

The O 0
association O 0
was O 0
stronger O 0
with O 0
longer O 0
duration O 0
of O 0
use O 0
when O 0
compared O 0
to O 0
shorter O 0
duration O 0
of O 0
use O 0
and O 0
was O 0
more O 0
pronounced O 0
in O 0
recent O 0
users O 0
than O 0
in O 0
remote O 0
users O 0
. O 0

An O 0
unexpectedly O 0
high O 0
( O 0
11 O 0
. O 0
4 O 0
% O 0
) O 0
number O 0
of O 0
patients O 0
with O 0
SPH O 0
had O 0
used O 0
anorexigens O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
magnitude O 0
of O 0
the O 0
association O 0
with O 0
PPH B-Disease 0
, O 0
the O 0
increase O 0
of O 0
association O 0
with O 0
increasing O 0
duration O 0
of O 0
use O 0
, O 0
and O 0
the O 0
specificity O 0
for O 0
fenfluramines B-Chemical 0
are O 0
consistent O 0
with O 0
previous O 0
studies O 0
indicating O 0
that O 0
fenfluramines B-Chemical 0
are O 0
causally O 0
related O 0
to O 0
PPH B-Disease 0
. O 0

The O 0
high O 0
prevalence O 0
of O 0
anorexigen O 0
use O 0
in O 0
patients O 0
with O 0
SPH O 0
also O 0
raises O 0
the O 0
possibility O 0
that O 0
these O 0
drugs O 0
precipitate O 0
pulmonary B-Disease 0
hypertension I-Disease 0
in O 0
patients O 0
with O 0
underlying O 0
conditions O 0
associated O 0
with O 0
SPH O 0
. O 0

Clinical O 0
aspects O 0
of O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
and O 0
thrombosis B-Disease 0
and O 0
other O 0
side O 0
effects O 0
of O 0
heparin B-Chemical 0
therapy O 0
. O 0

Heparin B-Chemical 0
, O 0
first O 0
used O 0
to O 0
prevent O 0
the O 0
clotting O 0
of O 0
blood O 0
in O 0
vitro O 0
, O 0
has O 0
been O 0
clinically O 0
used O 0
to O 0
treat O 0
thrombosis B-Disease 0
for O 0
more O 0
than O 0
50 O 0
years O 0
. O 0

Although O 0
several O 0
new O 0
anticoagulant O 0
drugs O 0
are O 0
in O 0
development O 0
, O 0
heparin B-Chemical 0
remains O 0
the O 0
anticoagulant O 0
of O 0
choice O 0
to O 0
treat O 0
acute O 0
thrombotic B-Disease 0
episodes O 0
. O 0

The O 0
clinical O 0
effects O 0
of O 0
heparin B-Chemical 0
are O 0
meritorious O 0
, O 0
but O 0
side O 0
effects O 0
do O 0
exist O 0
. O 0

Bleeding B-Disease 0
is O 0
the O 0
primary O 0
untoward O 0
effect O 0
of O 0
heparin B-Chemical 0
. O 0

Major O 0
bleeding B-Disease 0
is O 0
of O 0
primary O 0
concern O 0
in O 0
patients O 0
receiving O 0
heparin B-Chemical 0
therapy O 0
. O 0

However O 0
, O 0
additional O 0
important O 0
untoward O 0
effects O 0
of O 0
heparin B-Chemical 0
therapy O 0
include O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
, O 0
heparin B-Chemical 0
- O 0
associated O 0
osteoporosis B-Disease 0
, O 0
eosinophilia B-Disease 0
, O 0
skin B-Disease 0
reactions I-Disease 0
, O 0
allergic B-Disease 0
reactions I-Disease 0
other O 0
than O 0
thrombocytopenia B-Disease 0
, O 0
alopecia B-Disease 0
, O 0
transaminasemia O 0
, O 0
hyperkalemia B-Disease 0
, O 0
hypoaldosteronism B-Disease 0
, O 0
and O 0
priapism B-Disease 0
. O 0

These O 0
side O 0
effects O 0
are O 0
relatively O 0
rare O 0
in O 0
a O 0
given O 0
individual O 0
, O 0
but O 0
given O 0
the O 0
extremely O 0
widespread O 0
use O 0
of O 0
heparin B-Chemical 0
, O 0
some O 0
are O 0
quite O 0
common O 0
, O 0
particularly O 0
HITT B-Disease 0
and O 0
osteoporosis B-Disease 0
. O 0

Although O 0
reasonable O 0
incidences O 0
of O 0
many O 0
of O 0
these O 0
side O 0
effects O 0
can O 0
be O 0
" O 0
softly O 0
" O 0
deduced O 0
from O 0
current O 0
reports O 0
dealing O 0
with O 0
unfractionated O 0
heparin B-Chemical 0
, O 0
at O 0
present O 0
the O 0
incidences O 0
of O 0
these O 0
side O 0
effects O 0
with O 0
newer O 0
low O 0
molecular O 0
weight O 0
heparins B-Chemical 0
appear O 0
to O 0
be O 0
much O 0
less O 0
common O 0
. O 0

However O 0
, O 0
only O 0
longer O 0
experience O 0
will O 0
more O 0
clearly O 0
define O 0
the O 0
incidence O 0
of O 0
each O 0
side O 0
effect O 0
with O 0
low O 0
molecular O 0
weight O 0
preparations O 0
. O 0

A O 0
case O 0
of O 0
bilateral O 0
optic B-Disease 0
neuropathy I-Disease 0
in O 0
a O 0
patient O 0
on O 0
tacrolimus B-Chemical 0
( O 0
FK506 B-Chemical 0
) O 0
therapy O 0
after O 0
liver O 0
transplantation O 0
. O 0

PURPOSE O 0
: O 0
To O 0
report O 0
a O 0
case O 0
of O 0
bilateral O 0
optic B-Disease 0
neuropathy I-Disease 0
in O 0
a O 0
patient O 0
receiving O 0
tacrolimus B-Chemical 0
( O 0
FK B-Chemical 0
506 I-Chemical 0
, O 0
Prograf O 0
; O 0
Fujisawa O 0
USA O 0
, O 0
Inc O 0
, O 0
Deerfield O 0
, O 0
Illinois O 0
) O 0
for O 0
immunosuppression O 0
after O 0
orthotropic O 0
liver O 0
transplantation O 0
. O 0

METHOD O 0
: O 0
Case O 0
report O 0
. O 0

In O 0
a O 0
58 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
receiving O 0
tacrolimus B-Chemical 0
after O 0
orthotropic O 0
liver O 0
transplantation O 0
, O 0
serial O 0
neuro O 0
- O 0
ophthalmologic O 0
examinations O 0
and O 0
laboratory O 0
studies O 0
were O 0
performed O 0
. O 0

RESULTS O 0
: O 0
The O 0
patient O 0
had O 0
episodic O 0
deterioration O 0
of O 0
vision O 0
in O 0
both O 0
eyes O 0
, O 0
with O 0
clinical O 0
features O 0
resembling O 0
ischemic B-Disease 0
optic I-Disease 0
neuropathies I-Disease 0
. O 0

Deterioration B-Disease 0
of I-Disease 0
vision I-Disease 0
occurred O 0
despite O 0
discontinuation O 0
of O 0
the O 0
tacrolimus B-Chemical 0
. O 0

CONCLUSION O 0
: O 0
Tacrolimus B-Chemical 0
and O 0
other O 0
immunosuppressive O 0
agents O 0
may O 0
be O 0
associated O 0
with O 0
optic B-Disease 0
nerve I-Disease 0
toxicity I-Disease 0
. O 0

Hypercalcemia B-Disease 0
, O 0
arrhythmia B-Disease 0
, O 0
and O 0
mood O 0
stabilizers O 0
. O 0

Recent O 0
findings O 0
in O 0
a O 0
bipolar B-Disease 0
patient O 0
receiving O 0
maintenance O 0
lithium B-Chemical 0
therapy O 0
who O 0
developed O 0
hypercalcemia B-Disease 0
and O 0
severe O 0
bradyarrhythmia B-Disease 0
prompted O 0
the O 0
authors O 0
to O 0
conduct O 0
a O 0
retrospective O 0
study O 0
of O 0
bipolar B-Disease 0
patients O 0
with O 0
lithium B-Chemical 0
- O 0
associated O 0
hypercalcemia B-Disease 0
. O 0

A O 0
printout O 0
of O 0
all O 0
cases O 0
of O 0
hypercalcemia B-Disease 0
that O 0
presented O 0
during O 0
a O 0
1 O 0
- O 0
year O 0
period O 0
was O 0
generated O 0
. O 0

After O 0
eliminating O 0
spurious O 0
hypercalcemias B-Disease 0
or O 0
those O 0
associated O 0
with O 0
intravenous O 0
fluids O 0
, O 0
the O 0
authors O 0
identified O 0
18 O 0
non O 0
- O 0
lithium B-Chemical 0
- O 0
treated O 0
patients O 0
with O 0
hypercalcemias B-Disease 0
related O 0
to O 0
malignancies B-Disease 0
and O 0
other O 0
medical O 0
conditions O 0
( O 0
group O 0
A O 0
) O 0
and O 0
12 O 0
patients O 0
with O 0
lithium B-Chemical 0
- O 0
associated O 0
hypercalcemia B-Disease 0
( O 0
group O 0
B O 0
) O 0
. O 0

Patients O 0
in O 0
group O 0
B O 0
were O 0
not O 0
comparable O 0
to O 0
those O 0
in O 0
group O 0
A O 0
, O 0
as O 0
the O 0
latter O 0
were O 0
medically O 0
compromised O 0
and O 0
were O 0
receiving O 0
multiple O 0
pharmacotherapies O 0
. O 0

Thus O 0
, O 0
two O 0
control O 0
groups O 0
were O 0
generated O 0
: O 0
group O 0
C1 O 0
, O 0
which O 0
included O 0
age O 0
- O 0
and O 0
sex O 0
- O 0
comparable O 0
lithium B-Chemical 0
- O 0
treated O 0
bipolar B-Disease 0
normocalcemic O 0
patients O 0
, O 0
and O 0
group O 0
C2 O 0
, O 0
which O 0
included O 0
bipolar B-Disease 0
normocalcemic O 0
patients O 0
treated O 0
with O 0
anticonvulsant O 0
mood O 0
stabilizers O 0
. O 0

The O 0
electrocardiographic O 0
( O 0
ECG O 0
) O 0
findings O 0
for O 0
patients O 0
in O 0
group O 0
B O 0
were O 0
compared O 0
with O 0
those O 0
of O 0
patients O 0
in O 0
groups O 0
C1 O 0
and O 0
C2 O 0
. O 0

It O 0
was O 0
found O 0
that O 0
these O 0
groups O 0
did O 0
not O 0
differ O 0
in O 0
their O 0
overall O 0
frequency O 0
of O 0
ECG O 0
abnormalities O 0
; O 0
however O 0
, O 0
there O 0
were O 0
significant O 0
differences O 0
in O 0
the O 0
frequency O 0
of O 0
conduction O 0
defects O 0
. O 0

Patients O 0
with O 0
hypercalcemia B-Disease 0
resulting O 0
from O 0
medical O 0
diseases O 0
and O 0
bipolar B-Disease 0
patients O 0
with O 0
lithium B-Chemical 0
- O 0
associated O 0
hypercalcemia B-Disease 0
had O 0
significantly O 0
higher O 0
frequencies O 0
of O 0
conduction O 0
defects O 0
. O 0

Patients O 0
in O 0
group O 0
A O 0
had O 0
significant O 0
mortality O 0
at O 0
2 O 0
- O 0
year O 0
follow O 0
- O 0
up O 0
( O 0
28 O 0
% O 0
) O 0
, O 0
in O 0
contrast O 0
to O 0
zero O 0
mortality O 0
in O 0
the O 0
other O 0
three O 0
groups O 0
. O 0

The O 0
clinical O 0
implications O 0
of O 0
these O 0
findings O 0
are O 0
discussed O 0
. O 0

Attenuation O 0
of O 0
nephrotoxicity B-Disease 0
by O 0
a O 0
novel O 0
lipid O 0
nanosphere O 0
( O 0
NS O 0
- O 0
718 O 0
) O 0
incorporating O 0
amphotericin B-Chemical 0
B I-Chemical 0
. O 0

NS O 0
- O 0
718 O 0
, O 0
a O 0
lipid O 0
nanosphere O 0
incorporating O 0
amphotericin B-Chemical 0
B I-Chemical 0
, O 0
is O 0
effective O 0
against O 0
pathogenic O 0
fungi O 0
and O 0
has O 0
low O 0
toxicity B-Disease 0
. O 0

We O 0
compared O 0
the O 0
toxicity B-Disease 0
of O 0
NS O 0
- O 0
718 O 0
with O 0
that O 0
of O 0
Fungizone B-Chemical 0
( O 0
amphotericin B-Chemical 0
B I-Chemical 0
- I-Chemical 0
sodium I-Chemical 0
deoxycholate I-Chemical 0
; O 0
D B-Chemical 0
- I-Chemical 0
AmB I-Chemical 0
) O 0
in O 0
vitro O 0
using O 0
renal O 0
cell O 0
cultures O 0
and O 0
in O 0
vivo O 0
by O 0
biochemical O 0
analysis O 0
, O 0
histopathological O 0
study O 0
of O 0
the O 0
kidney O 0
and O 0
pharmacokinetic O 0
study O 0
of O 0
amphotericin B-Chemical 0
B I-Chemical 0
following O 0
intravenous O 0
infusion O 0
of O 0
the O 0
formulation O 0
in O 0
rats O 0
. O 0

Incubation O 0
with O 0
NS O 0
- O 0
718 O 0
resulted O 0
in O 0
significantly O 0
less O 0
damage O 0
of O 0
cultured O 0
human O 0
renal O 0
proximal O 0
tubular O 0
epithelial O 0
cells O 0
compared O 0
with O 0
D B-Chemical 0
- I-Chemical 0
AmB I-Chemical 0
. O 0

Serum O 0
blood O 0
urea B-Chemical 0
and O 0
creatinine B-Chemical 0
concentrations O 0
increased O 0
significantly O 0
in O 0
rats O 0
given O 0
an O 0
iv O 0
infusion O 0
of O 0
D B-Chemical 0
- I-Chemical 0
AmB I-Chemical 0
3 O 0
mg O 0
/ O 0
kg O 0
but O 0
not O 0
in O 0
those O 0
given O 0
the O 0
same O 0
dose O 0
of O 0
NS O 0
- O 0
718 O 0
. O 0

Histopathological O 0
examination O 0
of O 0
the O 0
kidney O 0
showed O 0
tubular B-Disease 0
necrosis I-Disease 0
in O 0
D B-Chemical 0
- I-Chemical 0
AmB I-Chemical 0
- O 0
treated O 0
rats O 0
but O 0
no O 0
change O 0
in O 0
NS O 0
- O 0
718 O 0
- O 0
treated O 0
rats O 0
. O 0

Amphotericin B-Chemical 0
B I-Chemical 0
concentrations O 0
in O 0
the O 0
kidney O 0
in O 0
NS O 0
- O 0
718 O 0
- O 0
treated O 0
rats O 0
were O 0
higher O 0
than O 0
those O 0
in O 0
D B-Chemical 0
- I-Chemical 0
AmB I-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

Our O 0
in O 0
vitro O 0
and O 0
in O 0
vivo O 0
results O 0
suggest O 0
that O 0
incorporation O 0
of O 0
amphotericin B-Chemical 0
B I-Chemical 0
into O 0
lipid O 0
nanospheres O 0
of O 0
NS O 0
- O 0
718 O 0
attenuates O 0
the O 0
nephrotoxicity B-Disease 0
of O 0
amphotericin B-Chemical 0
B I-Chemical 0
. O 0

Patterns O 0
of O 0
sulfadiazine B-Chemical 0
acute B-Disease 0
nephrotoxicity I-Disease 0
. O 0

Sulfadiazine B-Chemical 0
acute B-Disease 0
nephrotoxicity I-Disease 0
is O 0
reviving O 0
specially O 0
because O 0
of O 0
its O 0
use O 0
in O 0
toxoplasmosis B-Disease 0
in O 0
HIV O 0
- O 0
positive O 0
patients O 0
. O 0

We O 0
report O 0
4 O 0
cases O 0
, O 0
one O 0
of O 0
them O 0
in O 0
a O 0
previously O 0
healthy O 0
person O 0
. O 0

Under O 0
treatment O 0
with O 0
sulfadiazine B-Chemical 0
they O 0
developed O 0
oliguria B-Disease 0
, O 0
abdominal B-Disease 0
pain I-Disease 0
, O 0
renal B-Disease 0
failure I-Disease 0
and O 0
showed O 0
multiple O 0
radiolucent O 0
renal B-Disease 0
calculi I-Disease 0
in O 0
echography O 0
. O 0

All O 0
patients O 0
recovered O 0
their O 0
previous O 0
normal O 0
renal O 0
function O 0
after O 0
adequate O 0
hydration O 0
and O 0
alcalinization O 0
. O 0

A O 0
nephrostomy O 0
tube O 0
had O 0
to O 0
be O 0
placed O 0
in O 0
one O 0
of O 0
the O 0
patients O 0
for O 0
ureteral B-Disease 0
lithiasis I-Disease 0
in O 0
a O 0
single O 0
functional O 0
kidney O 0
. O 0

None O 0
of O 0
them O 0
needed O 0
dialysis O 0
or O 0
a O 0
renal O 0
biopsy O 0
because O 0
of O 0
a O 0
typical O 0
benign O 0
course O 0
. O 0

Treatment O 0
with O 0
sulfadiazine B-Chemical 0
requires O 0
exquisite O 0
control O 0
of O 0
renal O 0
function O 0
, O 0
an O 0
increase O 0
in O 0
water O 0
ingestion O 0
and O 0
possibly O 0
the O 0
alcalinization O 0
of O 0
the O 0
urine O 0
. O 0

We O 0
communicate O 0
a O 0
case O 0
in O 0
a O 0
previously O 0
healthy O 0
person O 0
, O 0
a O 0
fact O 0
not O 0
found O 0
in O 0
the O 0
recent O 0
literature O 0
. O 0

Probably O 0
many O 0
more O 0
cases O 0
are O 0
not O 0
detected O 0
. O 0

We O 0
think O 0
that O 0
a O 0
prospective O 0
study O 0
would O 0
be O 0
useful O 0
. O 0

Downbeat B-Disease 0
nystagmus I-Disease 0
associated O 0
with O 0
intravenous O 0
patient O 0
- O 0
controlled O 0
administration O 0
of O 0
morphine B-Chemical 0
. O 0

IMPLICATIONS O 0
: O 0
This O 0
case O 0
documents O 0
a O 0
patient O 0
who O 0
developed O 0
dizziness B-Disease 0
with O 0
downbeating B-Disease 0
nystagmus I-Disease 0
while O 0
receiving O 0
a O 0
relatively O 0
large O 0
dose O 0
of O 0
IV O 0
patient O 0
- O 0
controlled O 0
analgesia O 0
morphine B-Chemical 0
. O 0

Although O 0
there O 0
have O 0
been O 0
case O 0
reports O 0
of O 0
epidural O 0
morphine B-Chemical 0
with O 0
these O 0
symptoms O 0
and O 0
signs O 0
, O 0
this O 0
has O 0
not O 0
been O 0
previously O 0
documented O 0
with O 0
IV O 0
or O 0
patient O 0
- O 0
controlled O 0
analgesia O 0
morphine B-Chemical 0
. O 0

Hemodynamic O 0
and O 0
antiadrenergic O 0
effects O 0
of O 0
dronedarone B-Chemical 0
and O 0
amiodarone B-Chemical 0
in O 0
animals O 0
with O 0
a O 0
healed O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

The O 0
hemodynamic O 0
and O 0
antiadrenergic O 0
effects O 0
of O 0
dronedarone B-Chemical 0
, O 0
a O 0
noniodinated O 0
compound O 0
structurally O 0
related O 0
to O 0
amiodarone B-Chemical 0
, O 0
were O 0
compared O 0
with O 0
those O 0
of O 0
amiodarone B-Chemical 0
after O 0
prolonged O 0
oral O 0
administration O 0
, O 0
both O 0
at O 0
rest O 0
and O 0
during O 0
sympathetic O 0
stimulation O 0
in O 0
conscious O 0
dogs O 0
with O 0
a O 0
healed O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

All O 0
dogs O 0
( O 0
n O 0
= O 0
6 O 0
) O 0
randomly O 0
received O 0
orally O 0
dronedarone B-Chemical 0
( O 0
10 O 0
and O 0
30 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
amiodarone B-Chemical 0
( O 0
10 O 0
and O 0
30 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
and O 0
placebo O 0
twice O 0
daily O 0
for O 0
7 O 0
days O 0
, O 0
with O 0
a O 0
3 O 0
- O 0
week O 0
washout O 0
between O 0
consecutive O 0
treatments O 0
. O 0

Heart O 0
rate O 0
( O 0
HR O 0
) O 0
, O 0
mean O 0
arterial O 0
pressure O 0
( O 0
MBP O 0
) O 0
, O 0
positive O 0
rate O 0
of O 0
increase O 0
of O 0
left O 0
ventricular O 0
pressure O 0
( O 0
+ O 0
LVdP O 0
/ O 0
dt O 0
) O 0
, O 0
echocardiographically O 0
assessed O 0
left O 0
ventricular O 0
ejection O 0
fraction O 0
( O 0
LVEF O 0
) O 0
, O 0
and O 0
fractional O 0
shortening O 0
( O 0
FS O 0
) O 0
, O 0
as O 0
well O 0
as O 0
chronotropic O 0
response O 0
to O 0
isoproterenol B-Chemical 0
and O 0
exercise O 0
- O 0
induced O 0
sympathetic O 0
stimulation O 0
were O 0
evaluated O 0
under O 0
baseline O 0
and O 0
posttreatment O 0
conditions O 0
. O 0

Resting O 0
values O 0
of O 0
LVEF O 0
, O 0
FS O 0
, O 0
+ O 0
LVdP O 0
/ O 0
dt O 0
, O 0
and O 0
MBP O 0
remained O 0
unchanged O 0
whatever O 0
the O 0
drug O 0
and O 0
the O 0
dosing O 0
regimen O 0
, O 0
whereas O 0
resting O 0
HR O 0
was O 0
significantly O 0
and O 0
dose O 0
- O 0
dependently O 0
lowered O 0
after O 0
dronedarone B-Chemical 0
and O 0
to O 0
a O 0
lesser O 0
extent O 0
after O 0
amiodarone B-Chemical 0
. O 0

Both O 0
dronedarone B-Chemical 0
and O 0
amiodarone B-Chemical 0
significantly O 0
reduced O 0
the O 0
exercise O 0
- O 0
induced O 0
tachycardia B-Disease 0
and O 0
, O 0
at O 0
the O 0
highest O 0
dose O 0
, O 0
decreased O 0
the O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
tachycardia B-Disease 0
. O 0

Thus O 0
, O 0
dronedarone B-Chemical 0
and O 0
amiodarone B-Chemical 0
displayed O 0
a O 0
similar O 0
level O 0
of O 0
antiadrenergic O 0
effect O 0
and O 0
did O 0
not O 0
impair O 0
the O 0
resting O 0
left O 0
ventricular O 0
function O 0
. O 0

Consequently O 0
, O 0
dronedarone B-Chemical 0
might O 0
be O 0
particularly O 0
suitable O 0
for O 0
the O 0
treatment O 0
and O 0
prevention O 0
of O 0
various O 0
clinical O 0
arrhythmias B-Disease 0
, O 0
without O 0
compromising O 0
the O 0
left O 0
ventricular O 0
function O 0
. O 0

Phase O 0
2 O 0
trial O 0
of O 0
liposomal O 0
doxorubicin B-Chemical 0
( O 0
40 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
) O 0
in O 0
platinum B-Chemical 0
/ O 0
paclitaxel B-Chemical 0
- O 0
refractory O 0
ovarian B-Disease 0
and I-Disease 0
fallopian I-Disease 0
tube I-Disease 0
cancers I-Disease 0
and O 0
primary O 0
carcinoma B-Disease 0
of I-Disease 0
the I-Disease 0
peritoneum I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Several O 0
studies O 0
have O 0
demonstrated O 0
liposomal O 0
doxorubicin B-Chemical 0
( O 0
Doxil B-Chemical 0
) O 0
to O 0
be O 0
an O 0
active O 0
antineoplastic O 0
agent O 0
in O 0
platinum B-Chemical 0
- O 0
resistant O 0
ovarian B-Disease 0
cancer I-Disease 0
, O 0
with O 0
dose O 0
limiting O 0
toxicity B-Disease 0
of O 0
the O 0
standard O 0
dosing O 0
regimen O 0
( O 0
50 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
q O 0
4 O 0
weeks O 0
) O 0
being O 0
severe O 0
erythrodysesthesia B-Disease 0
( O 0
" O 0
hand B-Disease 0
- I-Disease 0
foot I-Disease 0
syndrome I-Disease 0
" O 0
) O 0
and O 0
stomatitis B-Disease 0
. O 0

We O 0
wished O 0
to O 0
develop O 0
a O 0
more O 0
tolerable O 0
liposomal O 0
doxorubicin B-Chemical 0
treatment O 0
regimen O 0
and O 0
document O 0
its O 0
level O 0
of O 0
activity O 0
in O 0
a O 0
well O 0
- O 0
defined O 0
patient O 0
population O 0
with O 0
platinum B-Chemical 0
/ O 0
paclitaxel B-Chemical 0
- O 0
refractory O 0
disease O 0
. O 0

METHODS O 0
AND O 0
MATERIALS O 0
: O 0
Patients O 0
with O 0
ovarian B-Disease 0
or I-Disease 0
fallopian I-Disease 0
tube I-Disease 0
cancers I-Disease 0
or O 0
primary O 0
peritoneal B-Disease 0
carcinoma I-Disease 0
with O 0
platinum B-Chemical 0
/ O 0
paclitaxel B-Chemical 0
- O 0
refractory O 0
disease O 0
( O 0
stable O 0
or O 0
progressive O 0
disease O 0
following O 0
treatment O 0
with O 0
these O 0
agents O 0
or O 0
previous O 0
objective O 0
response O 0
< O 0
3 O 0
months O 0
in O 0
duration O 0
) O 0
were O 0
treated O 0
with O 0
liposomal O 0
doxorubicin B-Chemical 0
at O 0
a O 0
dose O 0
of O 0
40 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
q O 0
4 O 0
weeks O 0
. O 0

RESULTS O 0
: O 0
A O 0
total O 0
of O 0
49 O 0
patients O 0
( O 0
median O 0
age O 0
: O 0
60 O 0
; O 0
range O 0
41 O 0
- O 0
81 O 0
) O 0
entered O 0
this O 0
phase O 0
2 O 0
trial O 0
. O 0

The O 0
median O 0
number O 0
of O 0
prior O 0
regimens O 0
was O 0
2 O 0
( O 0
range O 0
: O 0
1 O 0
- O 0
6 O 0
) O 0
. O 0

Six O 0
( O 0
12 O 0
% O 0
) O 0
and O 0
4 O 0
( O 0
8 O 0
% O 0
) O 0
patients O 0
experienced O 0
grade O 0
2 O 0
hand B-Disease 0
- I-Disease 0
foot I-Disease 0
syndrome I-Disease 0
and O 0
stomatitis B-Disease 0
, O 0
respectively O 0
( O 0
no O 0
episodes O 0
of O 0
grade O 0
3 O 0
) O 0
. O 0

One O 0
patient O 0
developed O 0
grade O 0
3 O 0
diarrhea B-Disease 0
requiring O 0
hospitalization O 0
for O 0
hydration O 0
. O 0

Six O 0
( O 0
12 O 0
% O 0
) O 0
individuals O 0
required O 0
dose O 0
reductions O 0
. O 0

The O 0
median O 0
number O 0
of O 0
courses O 0
of O 0
liposomal O 0
doxorubicin B-Chemical 0
administered O 0
on O 0
this O 0
protocol O 0
was O 0
2 O 0
( O 0
range O 0
: O 0
1 O 0
- O 0
12 O 0
) O 0
. O 0

Four O 0
of O 0
44 O 0
patients O 0
( O 0
9 O 0
% O 0
) O 0
evaluable O 0
for O 0
response O 0
exhibited O 0
objective O 0
and O 0
subjective O 0
evidence O 0
of O 0
an O 0
antineoplastic O 0
effect O 0
of O 0
therapy O 0
. O 0

CONCLUSION O 0
: O 0
This O 0
modified O 0
liposomal O 0
doxorubicin B-Chemical 0
regimen O 0
results O 0
in O 0
less O 0
toxicity B-Disease 0
( O 0
stomatitis B-Disease 0
, O 0
hand B-Disease 0
- I-Disease 0
foot I-Disease 0
syndrome I-Disease 0
) O 0
than O 0
the O 0
standard O 0
FDA O 0
- O 0
approved O 0
dose O 0
schedule O 0
. O 0

Definite O 0
, O 0
although O 0
limited O 0
, O 0
antineoplastic O 0
activity O 0
is O 0
observed O 0
in O 0
patients O 0
with O 0
well O 0
- O 0
defined O 0
platinum B-Chemical 0
- O 0
and O 0
paclitaxel B-Chemical 0
- O 0
refractory O 0
ovarian B-Disease 0
cancer I-Disease 0
. O 0

Efficacy O 0
of O 0
olanzapine B-Chemical 0
in O 0
acute O 0
bipolar B-Disease 0
mania I-Disease 0
: O 0
a O 0
double O 0
- O 0
blind O 0
, O 0
placebo O 0
- O 0
controlled O 0
study O 0
. O 0

The O 0
Olanzipine B-Chemical 0
HGGW O 0
Study O 0
Group O 0
. O 0

BACKGROUND O 0
: O 0
We O 0
compared O 0
the O 0
efficacy O 0
and O 0
safety O 0
of O 0
olanzapine B-Chemical 0
vs O 0
placebo O 0
for O 0
the O 0
treatment O 0
of O 0
acute O 0
bipolar B-Disease 0
mania I-Disease 0
. O 0

METHODS O 0
: O 0
Four O 0
- O 0
week O 0
, O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
parallel O 0
study O 0
. O 0

A O 0
total O 0
of O 0
115 O 0
patients O 0
with O 0
a O 0
DSM O 0
- O 0
IV O 0
diagnosis O 0
of O 0
bipolar B-Disease 0
disorder I-Disease 0
, O 0
manic B-Disease 0
or O 0
mixed O 0
, O 0
were O 0
randomized O 0
to O 0
olanzapine B-Chemical 0
, O 0
5 O 0
to O 0
20 O 0
mg O 0
/ O 0
d O 0
( O 0
n O 0
= O 0
55 O 0
) O 0
, O 0
or O 0
placebo O 0
( O 0
n O 0
= O 0
60 O 0
) O 0
. O 0

The O 0
primary O 0
efficacy O 0
measure O 0
was O 0
the O 0
Young O 0
- O 0
Mania B-Disease 0
Rating O 0
Scale O 0
( O 0
Y O 0
- O 0
MRS O 0
) O 0
total O 0
score O 0
. O 0

Response O 0
and O 0
euthymia O 0
were O 0
defined O 0
, O 0
a O 0
priori O 0
, O 0
as O 0
at O 0
least O 0
a O 0
50 O 0
% O 0
improvement O 0
from O 0
baseline O 0
to O 0
end O 0
point O 0
and O 0
as O 0
a O 0
score O 0
of O 0
no O 0
less O 0
than O 0
12 O 0
at O 0
end O 0
point O 0
in O 0
the O 0
Y O 0
- O 0
MRS O 0
total O 0
score O 0
, O 0
respectively O 0
. O 0

Safety O 0
was O 0
assessed O 0
using O 0
adverse O 0
events O 0
, O 0
Extrapyramidal B-Disease 0
Symptom I-Disease 0
( O 0
EPS B-Disease 0
) O 0
rating O 0
scales O 0
, O 0
laboratory O 0
values O 0
, O 0
electrocardiograms O 0
, O 0
vital O 0
signs O 0
, O 0
and O 0
weight O 0
change O 0
. O 0

RESULTS O 0
: O 0
Olanzapine B-Chemical 0
- O 0
treated O 0
patients O 0
demonstrated O 0
a O 0
statistically O 0
significant O 0
greater O 0
mean O 0
( O 0
+ O 0
/ O 0
- O 0
SD O 0
) O 0
improvement O 0
in O 0
Y O 0
- O 0
MRS O 0
total O 0
score O 0
than O 0
placebo O 0
- O 0
treated O 0
patients O 0
( O 0
- O 0
14 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
12 O 0
. O 0
5 O 0
and O 0
- O 0
8 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
12 O 0
. O 0
7 O 0
, O 0
respectively O 0
; O 0
P O 0
< O 0
. O 0
001 O 0
) O 0
, O 0
which O 0
was O 0
evident O 0
at O 0
the O 0
first O 0
postbaseline O 0
observation O 0
1 O 0
week O 0
after O 0
randomization O 0
and O 0
was O 0
maintained O 0
throughout O 0
the O 0
study O 0
( O 0
last O 0
observation O 0
carried O 0
forward O 0
) O 0
. O 0

Olanzapine B-Chemical 0
- O 0
treated O 0
patients O 0
demonstrated O 0
a O 0
higher O 0
rate O 0
of O 0
response O 0
( O 0
65 O 0
% O 0
vs O 0
43 O 0
% O 0
, O 0
respectively O 0
; O 0
P O 0
= O 0
. O 0
02 O 0
) O 0
and O 0
euthymia O 0
( O 0
61 O 0
% O 0
vs O 0
36 O 0
% O 0
, O 0
respectively O 0
; O 0
P O 0
= O 0
. O 0
01 O 0
) O 0
than O 0
placebo O 0
- O 0
treated O 0
patients O 0
. O 0

There O 0
were O 0
no O 0
statistically O 0
significant O 0
differences O 0
in O 0
EPSs B-Disease 0
between O 0
groups O 0
. O 0

However O 0
, O 0
olanzapine B-Chemical 0
- O 0
treated O 0
patients O 0
had O 0
a O 0
statistically O 0
significant O 0
greater O 0
mean O 0
( O 0
+ O 0
/ O 0
- O 0
SD O 0
) O 0
weight B-Disease 0
gain I-Disease 0
than O 0
placebo O 0
- O 0
treated O 0
patients O 0
( O 0
2 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
8 O 0
vs O 0
0 O 0
. O 0
45 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
3 O 0
kg O 0
, O 0
respectively O 0
) O 0
and O 0
also O 0
experienced O 0
more O 0
treatment O 0
- O 0
emergent O 0
somnolence B-Disease 0
( O 0
21 O 0
patients O 0
[ O 0
38 O 0
. O 0
2 O 0
% O 0
] O 0
vs O 0
5 O 0
[ O 0
8 O 0
. O 0
3 O 0
% O 0
] O 0
, O 0
respectively O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
Olanzapine B-Chemical 0
demonstrated O 0
greater O 0
efficacy O 0
than O 0
placebo O 0
in O 0
the O 0
treatment O 0
of O 0
acute O 0
bipolar B-Disease 0
mania I-Disease 0
and O 0
was O 0
generally O 0
well O 0
tolerated O 0
. O 0

The O 0
effect O 0
of O 0
pupil B-Disease 0
dilation I-Disease 0
with O 0
tropicamide B-Chemical 0
on O 0
vision O 0
and O 0
driving O 0
simulator O 0
performance O 0
. O 0

PURPOSE O 0
: O 0
To O 0
assess O 0
the O 0
effect O 0
of O 0
pupil B-Disease 0
dilation I-Disease 0
on O 0
vision O 0
and O 0
driving O 0
ability O 0
. O 0

METHODS O 0
: O 0
A O 0
series O 0
of O 0
tests O 0
on O 0
various O 0
parameters O 0
of O 0
visual O 0
function O 0
and O 0
driving O 0
simulator O 0
performance O 0
were O 0
performed O 0
on O 0
12 O 0
healthy O 0
drivers O 0
, O 0
before O 0
and O 0
after O 0
pupil B-Disease 0
dilation I-Disease 0
using O 0
guttae O 0
tropicamide B-Chemical 0
1 O 0
% O 0
. O 0

A O 0
driving O 0
simulator O 0
( O 0
Transport O 0
Research O 0
Laboratory O 0
) O 0
was O 0
used O 0
to O 0
measure O 0
reaction O 0
time O 0
( O 0
RT O 0
) O 0
, O 0
speed O 0
maintenance O 0
and O 0
steering O 0
accuracy O 0
. O 0

Tests O 0
of O 0
basic O 0
visual O 0
function O 0
included O 0
high O 0
- O 0
and O 0
low O 0
- O 0
contrast O 0
visual O 0
acuity O 0
( O 0
HCVA O 0
and O 0
LCVA O 0
) O 0
, O 0
Pelli O 0
- O 0
Robson O 0
contrast O 0
threshold O 0
( O 0
CT O 0
) O 0
and O 0
Goldmann O 0
perimetry O 0
( O 0
FIELDS O 0
) O 0
. O 0

Useful O 0
Field O 0
of O 0
View O 0
( O 0
UFOV O 0
- O 0
- O 0
a O 0
test O 0
of O 0
visual O 0
attention O 0
) O 0
was O 0
also O 0
undertaken O 0
. O 0

The O 0
mean O 0
differences O 0
in O 0
the O 0
pre O 0
- O 0
and O 0
post O 0
- O 0
dilatation O 0
measurements O 0
were O 0
tested O 0
for O 0
statistical O 0
significance O 0
at O 0
the O 0
95 O 0
% O 0
level O 0
using O 0
one O 0
- O 0
tail O 0
paired O 0
t O 0
- O 0
tests O 0
. O 0

RESULTS O 0
: O 0
Pupillary B-Disease 0
dilation I-Disease 0
resulted O 0
in O 0
a O 0
statistically O 0
significant O 0
deterioration O 0
in O 0
CT O 0
and O 0
HCVA O 0
only O 0
. O 0

Five O 0
of O 0
12 O 0
drivers O 0
also O 0
exhibited O 0
deterioration O 0
in O 0
LCVA O 0
, O 0
CT O 0
and O 0
RT O 0
. O 0

Little O 0
evidence O 0
emerged O 0
for O 0
deterioration O 0
in O 0
FIELDS O 0
and O 0
UFOV O 0
. O 0

Also O 0
, O 0
7 O 0
of O 0
12 O 0
drivers O 0
appeared O 0
to O 0
adjust O 0
their O 0
driving O 0
behaviour O 0
by O 0
reducing O 0
their O 0
speed O 0
on O 0
the O 0
driving O 0
simulator O 0
, O 0
leading O 0
to O 0
improved O 0
steering O 0
accuracy O 0
. O 0

CONCLUSIONS O 0
: O 0
Pupillary B-Disease 0
dilation I-Disease 0
may O 0
lead O 0
to O 0
a O 0
decrease O 0
in O 0
vision O 0
and O 0
daylight O 0
driving O 0
performance O 0
in O 0
young O 0
people O 0
. O 0

A O 0
larger O 0
study O 0
, O 0
including O 0
a O 0
broader O 0
spectrum O 0
of O 0
subjects O 0
, O 0
is O 0
warranted O 0
before O 0
guidelines O 0
can O 0
be O 0
recommended O 0
. O 0

A O 0
case O 0
of O 0
isotretinoin B-Disease 0
embryopathy I-Disease 0
with O 0
bilateral O 0
anotia B-Disease 0
and O 0
Taussig B-Disease 0
- I-Disease 0
Bing I-Disease 0
malformation I-Disease 0
. O 0

We O 0
report O 0
a O 0
newborn O 0
infant O 0
with O 0
multiple O 0
congenital O 0
anomalies O 0
( O 0
anotia B-Disease 0
and O 0
Taussig B-Disease 0
- I-Disease 0
Bing I-Disease 0
malformation I-Disease 0
) O 0
due O 0
to O 0
exposure O 0
to O 0
isotretinoin B-Chemical 0
within O 0
the O 0
first O 0
trimester O 0
. O 0

In O 0
this O 0
paper O 0
we O 0
aim O 0
to O 0
draw O 0
to O 0
the O 0
fact O 0
that O 0
caution O 0
is O 0
needed O 0
when O 0
prescribing O 0
vitamin B-Chemical 0
A I-Chemical 0
- O 0
containing O 0
drugs O 0
to O 0
women O 0
of O 0
childbearing O 0
years O 0
. O 0

Effect O 0
of O 0
methoxamine B-Chemical 0
on O 0
maximum O 0
urethral O 0
pressure O 0
in O 0
women O 0
with O 0
genuine O 0
stress B-Disease 0
incontinence I-Disease 0
: O 0
a O 0
placebo O 0
- O 0
controlled O 0
, O 0
double O 0
- O 0
blind O 0
crossover O 0
study O 0
. O 0

The O 0
aim O 0
of O 0
the O 0
study O 0
was O 0
to O 0
evaluate O 0
the O 0
potential O 0
role O 0
for O 0
a O 0
selective O 0
alpha1 O 0
- O 0
adrenoceptor O 0
agonist O 0
in O 0
the O 0
treatment O 0
of O 0
urinary B-Disease 0
stress I-Disease 0
incontinence I-Disease 0
. O 0

A O 0
randomised O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
placebo O 0
- O 0
controlled O 0
, O 0
crossover O 0
study O 0
design O 0
was O 0
employed O 0
. O 0

Half O 0
log O 0
incremental O 0
doses O 0
of O 0
intravenous O 0
methoxamine B-Chemical 0
or O 0
placebo O 0
( O 0
saline O 0
) O 0
were O 0
administered O 0
to O 0
a O 0
group O 0
of O 0
women O 0
with O 0
genuine O 0
stress B-Disease 0
incontinence I-Disease 0
while O 0
measuring O 0
maximum O 0
urethral O 0
pressure O 0
( O 0
MUP O 0
) O 0
, O 0
blood O 0
pressure O 0
, O 0
heart O 0
rate O 0
, O 0
and O 0
symptomatic O 0
side O 0
effects O 0
. O 0

Methoxamine B-Chemical 0
evoked O 0
non O 0
- O 0
significant O 0
increases O 0
in O 0
MUP O 0
and O 0
diastolic O 0
blood O 0
pressure O 0
but O 0
caused O 0
a B-Disease 0
significant I-Disease 0
rise I-Disease 0
in I-Disease 0
systolic I-Disease 0
blood I-Disease 0
pressure I-Disease 0
and O 0
significant O 0
fall O 0
in O 0
heart O 0
rate O 0
at O 0
maximum O 0
dosage O 0
. O 0

Systemic O 0
side O 0
effects O 0
including O 0
piloerection O 0
, O 0
headache B-Disease 0
, O 0
and O 0
cold O 0
extremities O 0
were O 0
experienced O 0
in O 0
all O 0
subjects O 0
. O 0

The O 0
results O 0
indicate O 0
that O 0
the O 0
clinical O 0
usefulness O 0
of O 0
direct O 0
, O 0
peripherally O 0
acting O 0
sub O 0
- O 0
type O 0
- O 0
selective O 0
alpha1 O 0
- O 0
adrenoceptor O 0
agonists O 0
in O 0
the O 0
medical O 0
treatment O 0
of O 0
stress B-Disease 0
incontinence I-Disease 0
may O 0
be O 0
limited O 0
by O 0
associated O 0
piloerection O 0
and O 0
cardiovascular O 0
side O 0
effects O 0
. O 0

Hyperglycemic B-Disease 0
effect O 0
of O 0
amino B-Chemical 0
compounds O 0
structurally O 0
related O 0
to O 0
caproate B-Chemical 0
in O 0
rats O 0
. O 0

The O 0
chronic O 0
feeding O 0
of O 0
small O 0
amounts O 0
( O 0
0 O 0
. O 0
3 O 0
- O 0
3 O 0
% O 0
of O 0
diet O 0
weight O 0
) O 0
of O 0
certain O 0
amino B-Chemical 0
derivatives O 0
of O 0
caproate B-Chemical 0
resulted O 0
in O 0
hyperglycemia B-Disease 0
, O 0
an O 0
elevated O 0
glucose B-Chemical 0
tolerance O 0
curve O 0
and O 0
, O 0
occasionally O 0
, O 0
glucosuria B-Disease 0
. O 0

Effective O 0
compounds O 0
included O 0
norleucine B-Chemical 0
, O 0
norvaline B-Chemical 0
, O 0
glutamate B-Chemical 0
, O 0
epsilon B-Chemical 0
- I-Chemical 0
aminocaproate I-Chemical 0
, O 0
methionine B-Chemical 0
, O 0
and O 0
leucine B-Chemical 0
. O 0

Toleration O 0
of O 0
high O 0
doses O 0
of O 0
angiotensin B-Chemical 0
- I-Chemical 0
converting I-Chemical 0
enzyme I-Chemical 0
inhibitors I-Chemical 0
in O 0
patients O 0
with O 0
chronic O 0
heart B-Disease 0
failure I-Disease 0
: O 0
results O 0
from O 0
the O 0
ATLAS O 0
trial O 0
. O 0

The O 0
Assessment O 0
of O 0
Treatment O 0
with O 0
Lisinopril B-Chemical 0
and O 0
Survival O 0
. O 0

BACKGROUND O 0
: O 0
Treatment O 0
with O 0
angiotensin B-Chemical 0
- I-Chemical 0
converting I-Chemical 0
enzyme I-Chemical 0
( I-Chemical 0
ACE I-Chemical 0
) I-Chemical 0
inhibitors I-Chemical 0
reduces O 0
mortality O 0
and O 0
morbidity O 0
in O 0
patients O 0
with O 0
chronic O 0
heart B-Disease 0
failure I-Disease 0
( O 0
CHF B-Disease 0
) O 0
, O 0
but O 0
most O 0
affected O 0
patients O 0
are O 0
not O 0
receiving O 0
these O 0
agents O 0
or O 0
are O 0
being O 0
treated O 0
with O 0
doses O 0
lower O 0
than O 0
those O 0
found O 0
to O 0
be O 0
efficacious O 0
in O 0
trials O 0
, O 0
primarily O 0
because O 0
of O 0
concerns O 0
about O 0
the O 0
safety O 0
and O 0
tolerability O 0
of O 0
these O 0
agents O 0
, O 0
especially O 0
at O 0
the O 0
recommended O 0
doses O 0
. O 0

The O 0
present O 0
study O 0
examines O 0
the O 0
safety O 0
and O 0
tolerability O 0
of O 0
high O 0
- O 0
compared O 0
with O 0
low O 0
- O 0
dose O 0
lisinopril B-Chemical 0
in O 0
CHF B-Disease 0
. O 0

METHODS O 0
: O 0
The O 0
Assessment O 0
of O 0
Lisinopril B-Chemical 0
and O 0
Survival O 0
study O 0
was O 0
a O 0
multicenter O 0
, O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
trial O 0
in O 0
which O 0
patients O 0
with O 0
or O 0
without O 0
previous O 0
ACE B-Chemical 0
inhibitor I-Chemical 0
treatment O 0
were O 0
stabilized O 0
receiving O 0
medium O 0
- O 0
dose O 0
lisinopril B-Chemical 0
( O 0
12 O 0
. O 0
5 O 0
or O 0
15 O 0
. O 0
0 O 0
mg O 0
once O 0
daily O 0
[ O 0
OD O 0
] O 0
) O 0
for O 0
2 O 0
to O 0
4 O 0
weeks O 0
and O 0
then O 0
randomized O 0
to O 0
high O 0
- O 0
( O 0
35 O 0
. O 0
0 O 0
or O 0
32 O 0
. O 0
5 O 0
mg O 0
OD O 0
) O 0
or O 0
low O 0
- O 0
dose O 0
( O 0
5 O 0
. O 0
0 O 0
or O 0
2 O 0
. O 0
5 O 0
mg O 0
OD O 0
) O 0
groups O 0
. O 0

Patients O 0
with O 0
New O 0
York O 0
Heart O 0
Association O 0
classes O 0
II O 0
to O 0
IV O 0
CHF B-Disease 0
and O 0
left O 0
ventricular O 0
ejection O 0
fractions O 0
of O 0
no O 0
greater O 0
than O 0
0 O 0
. O 0
30 O 0
( O 0
n O 0
= O 0
3164 O 0
) O 0
were O 0
randomized O 0
and O 0
followed O 0
up O 0
for O 0
a O 0
median O 0
of O 0
46 O 0
months O 0
. O 0

We O 0
examined O 0
the O 0
occurrence O 0
of O 0
adverse O 0
events O 0
and O 0
the O 0
need O 0
for O 0
discontinuation O 0
and O 0
dose O 0
reduction O 0
during O 0
treatment O 0
, O 0
with O 0
a O 0
focus O 0
on O 0
hypotension B-Disease 0
and O 0
renal B-Disease 0
dysfunction I-Disease 0
. O 0

RESULTS O 0
: O 0
Of O 0
405 O 0
patients O 0
not O 0
previously O 0
receiving O 0
an O 0
ACE B-Chemical 0
inhibitor I-Chemical 0
, O 0
doses O 0
in O 0
only O 0
4 O 0
. O 0
2 O 0
% O 0
could O 0
not O 0
be O 0
titrated O 0
to O 0
the O 0
medium O 0
doses O 0
required O 0
for O 0
randomization O 0
because O 0
of O 0
symptoms O 0
possibly O 0
related O 0
to O 0
hypotension B-Disease 0
( O 0
2 O 0
. O 0
0 O 0
% O 0
) O 0
or O 0
because O 0
of O 0
renal B-Disease 0
dysfunction I-Disease 0
or O 0
hyperkalemia B-Disease 0
( O 0
2 O 0
. O 0
3 O 0
% O 0
) O 0
. O 0

Doses O 0
in O 0
more O 0
than O 0
90 O 0
% O 0
of O 0
randomized O 0
patients O 0
in O 0
the O 0
high O 0
- O 0
and O 0
low O 0
- O 0
dose O 0
groups O 0
were O 0
titrated O 0
to O 0
their O 0
assigned O 0
target O 0
, O 0
and O 0
the O 0
mean O 0
doses O 0
of O 0
blinded O 0
medication O 0
in O 0
both O 0
groups O 0
remained O 0
similar O 0
throughout O 0
the O 0
study O 0
. O 0

Withdrawals O 0
occurred O 0
in O 0
27 O 0
. O 0
1 O 0
% O 0
of O 0
the O 0
high O 0
- O 0
and O 0
30 O 0
. O 0
7 O 0
% O 0
of O 0
the O 0
low O 0
- O 0
dose O 0
groups O 0
. O 0

Subgroups O 0
presumed O 0
to O 0
be O 0
at O 0
higher O 0
risk O 0
for O 0
ACE B-Chemical 0
inhibitor I-Chemical 0
intolerance O 0
( O 0
blood O 0
pressure O 0
, O 0
< O 0
120 O 0
mm O 0
Hg O 0
; O 0
creatinine B-Chemical 0
, O 0
> O 0
or O 0
= O 0
132 O 0
. O 0
6 O 0
micromol O 0
/ O 0
L O 0
[ O 0
> O 0
or O 0
= O 0
1 O 0
. O 0
5 O 0
mg O 0
/ O 0
dL O 0
] O 0
; O 0
age O 0
, O 0
> O 0
or O 0
= O 0
70 O 0
years O 0
; O 0
and O 0
patients O 0
with O 0
diabetes B-Disease 0
) O 0
generally O 0
tolerated O 0
the O 0
high O 0
- O 0
dose O 0
strategy O 0
. O 0

CONCLUSIONS O 0
: O 0
These O 0
findings O 0
demonstrate O 0
that O 0
ACE B-Chemical 0
inhibitor I-Chemical 0
therapy O 0
in O 0
most O 0
patients O 0
with O 0
CHF B-Disease 0
can O 0
be O 0
successfully O 0
titrated O 0
to O 0
and O 0
maintained O 0
at O 0
high O 0
doses O 0
, O 0
and O 0
that O 0
more O 0
aggressive O 0
use O 0
of O 0
these O 0
agents O 0
is O 0
warranted O 0
. O 0

Cocaine B-Chemical 0
, O 0
ethanol B-Chemical 0
, O 0
and O 0
cocaethylene B-Chemical 0
cardiotoxity B-Disease 0
in O 0
an O 0
animal O 0
model O 0
of O 0
cocaine B-Disease 0
and I-Disease 0
ethanol I-Disease 0
abuse I-Disease 0
. O 0

OBJECTIVES O 0
: O 0
Simultaneous O 0
abuse B-Disease 0
of I-Disease 0
cocaine I-Disease 0
and I-Disease 0
ethanol I-Disease 0
affects O 0
12 O 0
million O 0
Americans O 0
annually O 0
. O 0

In O 0
combination O 0
, O 0
these O 0
substances O 0
are O 0
substantially O 0
more O 0
toxic O 0
than O 0
either O 0
drug O 0
alone O 0
. O 0

Their O 0
combined O 0
cardiac B-Disease 0
toxicity I-Disease 0
may O 0
be O 0
due O 0
to O 0
independent O 0
effects O 0
of O 0
each O 0
drug O 0
; O 0
however O 0
, O 0
they O 0
may O 0
also O 0
be O 0
due O 0
to O 0
cocaethylene B-Chemical 0
( O 0
CE B-Chemical 0
) O 0
, O 0
a O 0
cocaine B-Chemical 0
metabolite O 0
formed O 0
only O 0
in O 0
the O 0
presence O 0
of O 0
ethanol B-Chemical 0
. O 0

The O 0
purpose O 0
of O 0
this O 0
study O 0
was O 0
to O 0
delineate O 0
the O 0
role O 0
of O 0
CE B-Chemical 0
in O 0
the O 0
combined O 0
cardiotoxicity B-Disease 0
of O 0
cocaine B-Chemical 0
and O 0
ethanol B-Chemical 0
in O 0
a O 0
model O 0
simulating O 0
their O 0
abuse O 0
. O 0

METHODS O 0
: O 0
Twenty O 0
- O 0
three O 0
dogs O 0
were O 0
randomized O 0
to O 0
receive O 0
either O 0
1 O 0
) O 0
three O 0
intravenous O 0
( O 0
IV O 0
) O 0
boluses O 0
of O 0
cocaine B-Chemical 0
7 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
with O 0
ethanol B-Chemical 0
( O 0
1 O 0
g O 0
/ O 0
kg O 0
) O 0
as O 0
an O 0
IV O 0
infusion O 0
( O 0
C O 0
+ O 0
E O 0
, O 0
n O 0
= O 0
8 O 0
) O 0
, O 0
2 O 0
) O 0
three O 0
cocaine B-Chemical 0
boluses O 0
only O 0
( O 0
C O 0
, O 0
n O 0
= O 0
6 O 0
) O 0
, O 0
3 O 0
) O 0
ethanol B-Chemical 0
infusion O 0
only O 0
( O 0
E O 0
, O 0
n O 0
= O 0
5 O 0
) O 0
, O 0
or O 0
4 O 0
) O 0
placebo O 0
boluses O 0
and O 0
infusion O 0
( O 0
n O 0
= O 0
4 O 0
) O 0
. O 0

Hemodynamic O 0
measurements O 0
, O 0
electrocardiograms O 0
, O 0
and O 0
serum O 0
drug O 0
concentrations O 0
were O 0
obtained O 0
at O 0
baseline O 0
, O 0
and O 0
then O 0
at O 0
fixed O 0
time O 0
intervals O 0
after O 0
each O 0
drug O 0
was O 0
administered O 0
. O 0

RESULTS O 0
: O 0
Two O 0
of O 0
eight O 0
dogs O 0
in O 0
the O 0
C O 0
+ O 0
E O 0
group O 0
experienced O 0
cardiovascular B-Disease 0
collapse I-Disease 0
. O 0

The O 0
most O 0
dramatic O 0
hemodynamic O 0
changes O 0
occurred O 0
after O 0
each O 0
cocaine B-Chemical 0
bolus O 0
in O 0
the O 0
C O 0
+ O 0
E O 0
and O 0
C O 0
only O 0
groups O 0
; O 0
however O 0
, O 0
persistent O 0
hemodynamic O 0
changes O 0
occurred O 0
in O 0
the O 0
C O 0
+ O 0
E O 0
group O 0
. O 0

Peak O 0
CE B-Chemical 0
levels O 0
were O 0
associated O 0
with O 0
a O 0
45 O 0
% O 0
( O 0
SD O 0
+ O 0
/ O 0
- O 0
22 O 0
% O 0
, O 0
95 O 0
% O 0
CI O 0
= O 0
22 O 0
% O 0
to O 0
69 O 0
% O 0
) O 0
decrease B-Disease 0
in I-Disease 0
cardiac I-Disease 0
output I-Disease 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
, O 0
a O 0
56 O 0
% O 0
( O 0
SD O 0
+ O 0
/ O 0
- O 0
23 O 0
% O 0
, O 0
95 O 0
% O 0
CI O 0
= O 0
32 O 0
% O 0
to O 0
80 O 0
% O 0
) O 0
decrease O 0
in O 0
dP O 0
/ O 0
dt O 0
( O 0
max O 0
) O 0
( O 0
p O 0
< O 0
. O 0
006 O 0
) O 0
, O 0
and O 0
a O 0
23 O 0
% O 0
( O 0
SD O 0
+ O 0
/ O 0
- O 0
15 O 0
% O 0
, O 0
95 O 0
% O 0
CI O 0
= O 0
7 O 0
% O 0
to O 0
49 O 0
% O 0
) O 0
decrease O 0
in O 0
SVO O 0
( O 0
2 O 0
) O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
025 O 0
) O 0
. O 0

Ventricular B-Disease 0
arrhythmias I-Disease 0
were O 0
primarily O 0
observed O 0
in O 0
the O 0
C O 0
+ O 0
E O 0
group O 0
, O 0
in O 0
which O 0
four O 0
of O 0
eight O 0
dogs O 0
experienced O 0
ventricular B-Disease 0
tachycardia I-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
Cocaine B-Chemical 0
and O 0
ethanol B-Chemical 0
in O 0
combination O 0
were O 0
more O 0
toxic O 0
than O 0
either O 0
substance O 0
alone O 0
. O 0

Co O 0
- O 0
administration O 0
resulted O 0
in O 0
prolonged O 0
cardiac B-Disease 0
toxicity I-Disease 0
and O 0
was O 0
dysrhythmogenic O 0
. O 0

Peak O 0
serum O 0
cocaethylene B-Chemical 0
concentrations O 0
were O 0
associated O 0
with O 0
prolonged O 0
myocardial B-Disease 0
depression I-Disease 0
. O 0

Worsening O 0
of O 0
Parkinsonism B-Disease 0
after O 0
the O 0
use O 0
of O 0
veralipride B-Chemical 0
for O 0
treatment O 0
of O 0
menopause O 0
: O 0
case O 0
report O 0
. O 0

We O 0
describe O 0
a O 0
female O 0
patient O 0
with O 0
stable O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
who O 0
has O 0
shown O 0
a O 0
marked O 0
worsening O 0
of O 0
her O 0
motor O 0
functions O 0
following O 0
therapy O 0
of O 0
menopause O 0
related O 0
symptoms O 0
with O 0
veralipride B-Chemical 0
, O 0
as O 0
well O 0
as O 0
the O 0
improvement O 0
of O 0
her O 0
symptoms O 0
back O 0
to O 0
baseline O 0
after O 0
discontinuation O 0
of O 0
the O 0
drug O 0
. O 0

We O 0
emphasize O 0
the O 0
anti O 0
- O 0
dopaminergic O 0
effect O 0
of O 0
veralipride B-Chemical 0
. O 0

Viracept B-Chemical 0
and O 0
irregular B-Disease 0
heartbeat I-Disease 0
warning O 0
. O 0

A O 0
group O 0
of O 0
doctors O 0
in O 0
Boston O 0
warn O 0
that O 0
the O 0
protease O 0
inhibitor O 0
Viracept B-Chemical 0
may O 0
cause O 0
an O 0
irregular B-Disease 0
heart I-Disease 0
beat I-Disease 0
, O 0
known O 0
as O 0
bradycardia B-Disease 0
, O 0
in O 0
people O 0
with O 0
HIV O 0
. O 0

Bradycardia B-Disease 0
occurred O 0
in O 0
a O 0
45 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
patient O 0
who O 0
was O 0
Viracept B-Chemical 0
in O 0
combination O 0
with O 0
other O 0
anti O 0
- O 0
HIV O 0
drugs O 0
. O 0

The O 0
symptoms O 0
ceased O 0
after O 0
switching O 0
to O 0
another O 0
drug O 0
combination O 0
. O 0

Frequency O 0
of O 0
appearance O 0
of O 0
myeloperoxidase O 0
- O 0
antineutrophil O 0
cytoplasmic O 0
antibody O 0
( O 0
MPO O 0
- O 0
ANCA O 0
) O 0
in O 0
Graves B-Disease 0
' I-Disease 0
disease I-Disease 0
patients O 0
treated O 0
with O 0
propylthiouracil B-Chemical 0
and O 0
the O 0
relationship O 0
between O 0
MPO O 0
- O 0
ANCA O 0
and O 0
clinical O 0
manifestations O 0
. O 0

OBJECTIVE O 0
: O 0
Myeloperoxidase O 0
antineutrophil O 0
cytoplasmic O 0
antibody O 0
( O 0
MPO O 0
- O 0
ANCA O 0
) O 0
- O 0
positive O 0
vasculitis B-Disease 0
has O 0
been O 0
reported O 0
in O 0
patients O 0
with O 0
Graves B-Disease 0
' I-Disease 0
disease I-Disease 0
who O 0
were O 0
treated O 0
with O 0
propylthiouracil B-Chemical 0
( O 0
PTU B-Chemical 0
) O 0
. O 0

The O 0
appearance O 0
of O 0
MPO O 0
- O 0
ANCA O 0
in O 0
these O 0
cases O 0
was O 0
suspected O 0
of O 0
being O 0
related O 0
to O 0
PTU B-Chemical 0
because O 0
the O 0
titres O 0
of O 0
MPO O 0
- O 0
ANCA O 0
decreased O 0
when O 0
PTU B-Chemical 0
was O 0
stopped O 0
. O 0

Nevertheless O 0
, O 0
there O 0
have O 0
been O 0
no O 0
studies O 0
on O 0
the O 0
temporal O 0
relationship O 0
between O 0
the O 0
appearance O 0
of O 0
MPO O 0
- O 0
ANCA O 0
and O 0
vasculitis B-Disease 0
during O 0
PTU B-Chemical 0
therapy O 0
, O 0
or O 0
on O 0
the O 0
incidence O 0
of O 0
MPO O 0
- O 0
ANCA O 0
in O 0
untreated O 0
Graves B-Disease 0
' I-Disease 0
disease I-Disease 0
patients O 0
. O 0

Therefore O 0
, O 0
we O 0
sought O 0
to O 0
address O 0
these O 0
parameters O 0
in O 0
patients O 0
with O 0
Graves B-Disease 0
' I-Disease 0
disease I-Disease 0
. O 0

PATIENTS O 0
: O 0
We O 0
investigated O 0
102 O 0
untreated O 0
patients O 0
with O 0
hyperthyroidism B-Disease 0
due O 0
to O 0
Graves B-Disease 0
' I-Disease 0
disease I-Disease 0
for O 0
the O 0
presence O 0
of O 0
MPO O 0
- O 0
ANCA O 0
, O 0
and O 0
for O 0
the O 0
development O 0
vasculitis B-Disease 0
after O 0
starting O 0
PTU B-Chemical 0
therapy O 0
. O 0

Twenty O 0
- O 0
nine O 0
of O 0
them O 0
were O 0
later O 0
excluded O 0
because O 0
of O 0
adverse O 0
effects O 0
of O 0
PTU B-Chemical 0
or O 0
because O 0
the O 0
observation O 0
period O 0
was O 0
less O 0
than O 0
3 O 0
months O 0
. O 0

The O 0
remaining O 0
73 O 0
patients O 0
( O 0
55 O 0
women O 0
and O 0
18 O 0
men O 0
) O 0
, O 0
all O 0
of O 0
whom O 0
were O 0
examined O 0
for O 0
more O 0
than O 0
3 O 0
months O 0
, O 0
were O 0
adopted O 0
as O 0
the O 0
subjects O 0
of O 0
the O 0
investigation O 0
. O 0

The O 0
median O 0
observation O 0
period O 0
was O 0
23 O 0
. O 0
6 O 0
months O 0
( O 0
range O 0
: O 0
3 O 0
- O 0
37 O 0
months O 0
) O 0
. O 0

MEASUREMENTS O 0
: O 0
MPO O 0
- O 0
ANCA O 0
was O 0
measured O 0
at O 0
intervals O 0
of O 0
2 O 0
- O 0
6 O 0
months O 0
. O 0

RESULTS O 0
: O 0
Before O 0
treatment O 0
, O 0
the O 0
MPO O 0
- O 0
ANCA O 0
titres O 0
of O 0
all O 0
102 O 0
untreated O 0
Graves B-Disease 0
' I-Disease 0
disease I-Disease 0
patients O 0
were O 0
within O 0
the O 0
reference O 0
range O 0
( O 0
below O 0
10 O 0
U O 0
/ O 0
ml O 0
) O 0
. O 0

Three O 0
( O 0
4 O 0
. O 0
1 O 0
% O 0
) O 0
of O 0
the O 0
73 O 0
patients O 0
were O 0
positive O 0
for O 0
MPO O 0
- O 0
ANCA O 0
at O 0
13 O 0
, O 0
16 O 0
and O 0
17 O 0
months O 0
, O 0
respectively O 0
, O 0
after O 0
the O 0
start O 0
of O 0
PTU B-Chemical 0
therapy O 0
. O 0

In O 0
two O 0
of O 0
them O 0
, O 0
the O 0
MPO O 0
- O 0
ANCA O 0
titres O 0
transiently O 0
increased O 0
to O 0
12 O 0
. O 0
8 O 0
and O 0
15 O 0
. O 0
0 O 0
U O 0
/ O 0
ml O 0
, O 0
respectively O 0
, O 0
despite O 0
continued O 0
PTU B-Chemical 0
therapy O 0
, O 0
but O 0
no O 0
vasculitic B-Disease 0
disorders I-Disease 0
developed O 0
. O 0

In O 0
the O 0
third O 0
patient O 0
, O 0
the O 0
MPO O 0
- O 0
ANCA O 0
titre O 0
increased O 0
to O 0
204 O 0
U O 0
/ O 0
ml O 0
and O 0
she O 0
developed O 0
a O 0
higher O 0
fever B-Disease 0
, O 0
oral B-Disease 0
ulcers I-Disease 0
and O 0
polyarthralgia B-Disease 0
, O 0
but O 0
the O 0
symptoms O 0
resolved O 0
2 O 0
weeks O 0
after O 0
stopping O 0
PTU B-Chemical 0
therapy O 0
, O 0
and O 0
the O 0
MPO O 0
- O 0
ANCA O 0
titre O 0
decreased O 0
to O 0
20 O 0
. O 0
7 O 0
U O 0
/ O 0
ml O 0
by O 0
4 O 0
months O 0
after O 0
discontinuing O 0
PTU B-Chemical 0
. O 0

CONCLUSIONS O 0
: O 0
PTU B-Chemical 0
therapy O 0
may O 0
be O 0
related O 0
to O 0
the O 0
appearance O 0
of O 0
MPO O 0
- O 0
ANCA O 0
, O 0
but O 0
MPO O 0
- O 0
ANCA O 0
does O 0
not O 0
appear O 0
to O 0
be O 0
closely O 0
related O 0
to O 0
vasculitis B-Disease 0
. O 0

Prevalence O 0
of O 0
heart B-Disease 0
disease I-Disease 0
in O 0
asymptomatic O 0
chronic O 0
cocaine B-Chemical 0
users O 0
. O 0

To O 0
determine O 0
the O 0
prevalence O 0
of O 0
heart B-Disease 0
disease I-Disease 0
in O 0
outpatient O 0
young O 0
asymptomatic O 0
chronic O 0
cocaine B-Chemical 0
users O 0
, O 0
35 O 0
cocaine B-Chemical 0
users O 0
and O 0
32 O 0
age O 0
- O 0
matched O 0
controls O 0
underwent O 0
resting O 0
and O 0
exercise O 0
electrocardiography O 0
( O 0
ECG O 0
) O 0
and O 0
Doppler O 0
echocardiography O 0
. O 0

Findings O 0
consistent O 0
with O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
were O 0
detected O 0
in O 0
12 O 0
( O 0
34 O 0
% O 0
) O 0
patients O 0
and O 0
3 O 0
( O 0
9 O 0
% O 0
) O 0
controls O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Decreased O 0
left O 0
ventricular O 0
systolic O 0
function O 0
was O 0
demonstrated O 0
in O 0
5 O 0
( O 0
14 O 0
% O 0
) O 0
patients O 0
, O 0
but O 0
in O 0
none O 0
of O 0
the O 0
controls O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
055 O 0
) O 0
. O 0

Finally O 0
, O 0
resting O 0
and O 0
peak O 0
exercise O 0
abnormal B-Disease 0
left I-Disease 0
ventricular I-Disease 0
filling I-Disease 0
was O 0
detected O 0
in O 0
38 O 0
and O 0
35 O 0
% O 0
of O 0
patients O 0
as O 0
compared O 0
to O 0
19 O 0
and O 0
9 O 0
% O 0
of O 0
controls O 0
, O 0
respectively O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
11 O 0
and O 0
0 O 0
. O 0
02 O 0
, O 0
respectively O 0
) O 0
. O 0

We O 0
conclude O 0
that O 0
coronary B-Disease 0
artery I-Disease 0
or I-Disease 0
myocardial I-Disease 0
disease I-Disease 0
is O 0
common O 0
( O 0
38 O 0
% O 0
) O 0
in O 0
young O 0
asymptomatic O 0
chronic O 0
cocaine B-Chemical 0
users O 0
. O 0

Therefore O 0
, O 0
screening O 0
ECG O 0
and O 0
echocardiography O 0
may O 0
be O 0
warranted O 0
in O 0
these O 0
patients O 0
. O 0

Cardioprotective O 0
effects O 0
of O 0
Picrorrhiza O 0
kurroa O 0
against O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
myocardial O 0
stress O 0
in O 0
rats O 0
. O 0

The O 0
cardioprotective O 0
effect O 0
of O 0
the O 0
ethanol B-Chemical 0
extract O 0
of O 0
Picrorrhiza O 0
kurroa O 0
rhizomes O 0
and O 0
roots O 0
( O 0
PK O 0
) O 0
on O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
myocardial B-Disease 0
infarction I-Disease 0
in O 0
rats O 0
with O 0
respect O 0
to O 0
lipid O 0
metabolism O 0
in O 0
serum O 0
and O 0
heart O 0
tissue O 0
has O 0
been O 0
investigated O 0
. O 0

Oral O 0
pre O 0
- O 0
treatment O 0
with O 0
PK O 0
( O 0
80 O 0
mg O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
day O 0
( O 0
- O 0
1 O 0
) O 0
for O 0
15 O 0
days O 0
) O 0
significantly O 0
prevented O 0
the O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
myocardial B-Disease 0
infarction I-Disease 0
and O 0
maintained O 0
the O 0
rats O 0
at O 0
near O 0
normal O 0
status O 0
. O 0

Phase O 0
2 O 0
early O 0
afterdepolarization O 0
as O 0
a O 0
trigger O 0
of O 0
polymorphic O 0
ventricular B-Disease 0
tachycardia I-Disease 0
in O 0
acquired O 0
long B-Disease 0
- I-Disease 0
QT I-Disease 0
syndrome I-Disease 0
: O 0
direct O 0
evidence O 0
from O 0
intracellular O 0
recordings O 0
in O 0
the O 0
intact O 0
left O 0
ventricular O 0
wall O 0
. O 0

BACKGROUND O 0
: O 0
This O 0
study O 0
examined O 0
the O 0
role O 0
of O 0
phase O 0
2 O 0
early O 0
afterdepolarization O 0
( O 0
EAD O 0
) O 0
in O 0
producing O 0
a O 0
trigger O 0
to O 0
initiate O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
( O 0
TdP B-Disease 0
) O 0
with O 0
QT B-Disease 0
prolongation I-Disease 0
induced O 0
by O 0
dl O 0
- O 0
sotalol B-Chemical 0
and O 0
azimilide B-Chemical 0
. O 0

The O 0
contribution O 0
of O 0
transmural O 0
dispersion O 0
of O 0
repolarization O 0
( O 0
TDR O 0
) O 0
to O 0
transmural O 0
propagation O 0
of O 0
EAD O 0
and O 0
the O 0
maintenance O 0
of O 0
TdP B-Disease 0
was O 0
also O 0
evaluated O 0
. O 0

METHODS O 0
AND O 0
RESULTS O 0
: O 0
Transmembrane O 0
action O 0
potentials O 0
from O 0
epicardium O 0
, O 0
midmyocardium O 0
, O 0
and O 0
endocardium O 0
were O 0
recorded O 0
simultaneously O 0
, O 0
together O 0
with O 0
a O 0
transmural O 0
ECG O 0
, O 0
in O 0
arterially O 0
perfused O 0
canine O 0
and O 0
rabbit O 0
left O 0
ventricular O 0
preparations O 0
. O 0

dl O 0
- O 0
Sotalol B-Chemical 0
preferentially O 0
prolonged O 0
action O 0
potential O 0
duration O 0
( O 0
APD O 0
) O 0
in O 0
M O 0
cells O 0
dose O 0
- O 0
dependently O 0
( O 0
1 O 0
to O 0
100 O 0
micromol O 0
/ O 0
L O 0
) O 0
, O 0
leading O 0
to O 0
QT B-Disease 0
prolongation I-Disease 0
and O 0
an O 0
increase O 0
in O 0
TDR O 0
. O 0

Azimilide B-Chemical 0
, O 0
however O 0
, O 0
significantly O 0
prolonged O 0
APD O 0
and O 0
QT O 0
interval O 0
at O 0
concentrations O 0
from O 0
0 O 0
. O 0
1 O 0
to O 0
10 O 0
micromol O 0
/ O 0
L O 0
but O 0
shortened O 0
them O 0
at O 0
30 O 0
micromol O 0
/ O 0
L O 0
. O 0

Unlike O 0
dl O 0
- O 0
sotalol B-Chemical 0
, O 0
azimilide B-Chemical 0
( O 0
> O 0
3 O 0
micromol O 0
/ O 0
L O 0
) O 0
increased O 0
epicardial O 0
APD O 0
markedly O 0
, O 0
causing O 0
a O 0
diminished O 0
TDR O 0
. O 0

Although O 0
both O 0
dl O 0
- O 0
sotalol B-Chemical 0
and O 0
azimilide B-Chemical 0
rarely O 0
induced O 0
EADs O 0
in O 0
canine O 0
left O 0
ventricles O 0
, O 0
they O 0
produced O 0
frequent O 0
EADs O 0
in O 0
rabbits O 0
, O 0
in O 0
which O 0
more O 0
pronounced O 0
QT B-Disease 0
prolongation I-Disease 0
was O 0
seen O 0
. O 0

An O 0
increase O 0
in O 0
TDR O 0
by O 0
dl O 0
- O 0
sotalol B-Chemical 0
facilitated O 0
transmural O 0
propagation O 0
of O 0
EADs O 0
that O 0
initiated O 0
multiple O 0
episodes O 0
of O 0
spontaneous O 0
TdP B-Disease 0
in O 0
3 O 0
of O 0
6 O 0
rabbit O 0
left O 0
ventricles O 0
. O 0

Of O 0
note O 0
, O 0
although O 0
azimilide B-Chemical 0
( O 0
3 O 0
to O 0
10 O 0
micromol O 0
/ O 0
L O 0
) O 0
increased O 0
APD O 0
more O 0
than O 0
dl O 0
- O 0
sotalol B-Chemical 0
, O 0
its O 0
EADs O 0
often O 0
failed O 0
to O 0
propagate O 0
transmurally O 0
, O 0
probably O 0
because O 0
of O 0
a O 0
diminished O 0
TDR O 0
. O 0

CONCLUSIONS O 0
: O 0
This O 0
study O 0
provides O 0
the O 0
first O 0
direct O 0
evidence O 0
from O 0
intracellular O 0
action O 0
potential O 0
recordings O 0
that O 0
phase O 0
2 O 0
EAD O 0
can O 0
be O 0
generated O 0
from O 0
intact O 0
ventricular O 0
wall O 0
and O 0
produce O 0
a O 0
trigger O 0
to O 0
initiate O 0
the O 0
onset O 0
of O 0
TdP B-Disease 0
under O 0
QT B-Disease 0
prolongation I-Disease 0
. O 0

A O 0
pilot O 0
study O 0
to O 0
assess O 0
the O 0
safety O 0
of O 0
dobutamine B-Chemical 0
stress O 0
echocardiography O 0
in O 0
the O 0
emergency O 0
department O 0
evaluation O 0
of O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
. O 0

STUDY O 0
OBJECTIVE O 0
: O 0
Chest B-Disease 0
pain I-Disease 0
in O 0
the O 0
setting O 0
of O 0
cocaine B-Chemical 0
use O 0
poses O 0
a O 0
diagnostic O 0
dilemma O 0
. O 0

Dobutamine B-Chemical 0
stress O 0
echocardiography O 0
( O 0
DSE O 0
) O 0
is O 0
a O 0
widely O 0
available O 0
and O 0
sensitive O 0
test O 0
for O 0
evaluating O 0
cardiac O 0
ischemia B-Disease 0
. O 0

Because O 0
of O 0
the O 0
theoretical O 0
concern O 0
regarding O 0
administration O 0
of O 0
dobutamine B-Chemical 0
in O 0
the O 0
setting O 0
of O 0
cocaine B-Chemical 0
use O 0
, O 0
we O 0
conducted O 0
a O 0
pilot O 0
study O 0
to O 0
assess O 0
the O 0
safety O 0
of O 0
DSE O 0
in O 0
emergency O 0
department O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
. O 0

METHODS O 0
: O 0
A O 0
prospective O 0
case O 0
series O 0
was O 0
conducted O 0
in O 0
the O 0
intensive O 0
diagnostic O 0
and O 0
treatment O 0
unit O 0
in O 0
the O 0
ED O 0
of O 0
an O 0
urban O 0
tertiary O 0
- O 0
care O 0
teaching O 0
hospital O 0
. O 0

Patients O 0
were O 0
eligible O 0
for O 0
DSE O 0
if O 0
they O 0
had O 0
used O 0
cocaine B-Chemical 0
within O 0
24 O 0
hours O 0
preceding O 0
the O 0
onset O 0
of O 0
chest B-Disease 0
pain I-Disease 0
and O 0
had O 0
a O 0
normal O 0
ECG O 0
and O 0
tropinin O 0
I O 0
level O 0
. O 0

Patients O 0
exhibiting O 0
signs O 0
of O 0
continuing O 0
cocaine B-Chemical 0
toxicity B-Disease 0
were O 0
excluded O 0
from O 0
the O 0
study O 0
. O 0

All O 0
patients O 0
were O 0
admitted O 0
to O 0
the O 0
hospital O 0
for O 0
serial O 0
testing O 0
after O 0
the O 0
DSE O 0
testing O 0
in O 0
the O 0
intensive O 0
diagnostic O 0
and O 0
treatment O 0
unit O 0
. O 0

RESULTS O 0
: O 0
Twenty O 0
- O 0
four O 0
patients O 0
were O 0
enrolled O 0
. O 0

Two O 0
patients O 0
had O 0
inadequate O 0
resting O 0
images O 0
, O 0
one O 0
DSE O 0
was O 0
terminated O 0
because O 0
of O 0
inferior O 0
hypokinesis B-Disease 0
, O 0
another O 0
DSE O 0
was O 0
terminated O 0
because O 0
of O 0
a O 0
rate O 0
- O 0
related O 0
atrial O 0
conduction O 0
deficit O 0
, O 0
and O 0
1 O 0
patient O 0
did O 0
not O 0
reach O 0
the O 0
target O 0
heart O 0
rate O 0
. O 0

Thus O 0
, O 0
19 O 0
patients O 0
completed O 0
a O 0
DSE O 0
and O 0
reached O 0
their O 0
target O 0
heart O 0
rates O 0
. O 0

None O 0
of O 0
the O 0
patients O 0
experienced O 0
signs O 0
of O 0
exaggerated O 0
adrenergic O 0
response O 0
, O 0
which O 0
was O 0
defined O 0
as O 0
a O 0
systolic O 0
blood O 0
pressure O 0
of O 0
greater O 0
than O 0
200 O 0
mm O 0
Hg O 0
or O 0
the O 0
occurrence O 0
of O 0
tachydysrhythmias B-Disease 0
( O 0
excluding O 0
sinus B-Disease 0
tachycardia I-Disease 0
) O 0
. O 0

Further O 0
suggesting O 0
lack O 0
of O 0
exaggerated O 0
adrenergic O 0
response O 0
, O 0
13 O 0
( O 0
65 O 0
% O 0
) O 0
of O 0
20 O 0
patients O 0
required O 0
supplemental O 0
atropine B-Chemical 0
to O 0
reach O 0
their O 0
target O 0
heart O 0
rates O 0
. O 0

CONCLUSION O 0
: O 0
No O 0
exaggerated O 0
adrenergic O 0
response O 0
was O 0
detected O 0
when O 0
dobutamine B-Chemical 0
was O 0
administered O 0
to O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
related O 0
chest B-Disease 0
pain I-Disease 0
. O 0

Prenatal O 0
cocaine B-Chemical 0
exposure O 0
and O 0
cranial O 0
sonographic O 0
findings O 0
in O 0
preterm B-Disease 0
infants I-Disease 0
. O 0

PURPOSE O 0
: O 0
Prenatal O 0
cocaine B-Chemical 0
exposure O 0
has O 0
been O 0
linked O 0
with O 0
subependymal O 0
hemorrhage B-Disease 0
and O 0
the O 0
formation O 0
of O 0
cysts B-Disease 0
that O 0
are O 0
detectable O 0
on O 0
cranial O 0
sonography O 0
in O 0
neonates O 0
born O 0
at O 0
term O 0
. O 0

We O 0
sought O 0
to O 0
determine O 0
if O 0
prenatal O 0
cocaine B-Chemical 0
exposure O 0
increases O 0
the O 0
incidence O 0
of O 0
subependymal B-Disease 0
cysts I-Disease 0
in O 0
preterm B-Disease 0
infants I-Disease 0
. O 0

METHODS O 0
: O 0
We O 0
retrospectively O 0
reviewed O 0
the O 0
medical O 0
records O 0
and O 0
cranial O 0
sonograms O 0
obtained O 0
during O 0
a O 0
1 O 0
- O 0
year O 0
period O 0
on O 0
122 O 0
premature B-Disease 0
( I-Disease 0
< I-Disease 0
36 I-Disease 0
weeks I-Disease 0
of I-Disease 0
gestation I-Disease 0
) I-Disease 0
infants I-Disease 0
. O 0

Infants O 0
were O 0
categorized O 0
into O 0
1 O 0
of O 0
2 O 0
groups O 0
: O 0
those O 0
exposed O 0
to O 0
cocaine B-Chemical 0
and O 0
those O 0
not O 0
exposed O 0
to O 0
cocaine B-Chemical 0
. O 0

Infants O 0
were O 0
assigned O 0
to O 0
the O 0
cocaine B-Chemical 0
- O 0
exposed O 0
group O 0
if O 0
there O 0
was O 0
a O 0
maternal O 0
history O 0
of O 0
cocaine B-Disease 0
abuse I-Disease 0
during O 0
pregnancy O 0
or O 0
if O 0
maternal O 0
or O 0
neonatal O 0
urine O 0
toxicology O 0
results O 0
were O 0
positive O 0
at O 0
the O 0
time O 0
of O 0
delivery O 0
. O 0

RESULTS O 0
: O 0
Five O 0
of O 0
the O 0
122 O 0
infants O 0
were O 0
excluded O 0
from O 0
the O 0
study O 0
because O 0
of O 0
insufficient O 0
medical O 0
and O 0
drug O 0
histories O 0
. O 0

The O 0
incidence O 0
of O 0
subependymal B-Disease 0
cysts I-Disease 0
in O 0
the O 0
117 O 0
remaining O 0
infants O 0
was O 0
14 O 0
% O 0
( O 0
16 O 0
of O 0
117 O 0
) O 0
. O 0

The O 0
incidence O 0
of O 0
subependymal B-Disease 0
cysts I-Disease 0
in O 0
infants O 0
exposed O 0
to O 0
cocaine B-Chemical 0
prenatally O 0
was O 0
44 O 0
% O 0
( O 0
8 O 0
of O 0
18 O 0
) O 0
compared O 0
with O 0
8 O 0
% O 0
( O 0
8 O 0
of O 0
99 O 0
) O 0
in O 0
the O 0
unexposed O 0
group O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
We O 0
found O 0
an O 0
increased O 0
incidence O 0
of O 0
subependymal B-Disease 0
cyst I-Disease 0
formation O 0
in O 0
preterm B-Disease 0
infants I-Disease 0
who O 0
were O 0
exposed O 0
to O 0
cocaine B-Chemical 0
prenatally O 0
. O 0

This O 0
result O 0
is O 0
consistent O 0
with O 0
results O 0
of O 0
similar O 0
studies O 0
in O 0
term O 0
infants O 0
. O 0

Thalidomide B-Chemical 0
neuropathy B-Disease 0
in O 0
patients O 0
treated O 0
for O 0
metastatic O 0
prostate B-Disease 0
cancer I-Disease 0
. O 0

We O 0
prospectively O 0
evaluated O 0
thalidomide B-Chemical 0
- O 0
induced O 0
neuropathy B-Disease 0
using O 0
electrodiagnostic O 0
studies O 0
. O 0

Sixty O 0
- O 0
seven O 0
men O 0
with O 0
metastatic O 0
androgen B-Chemical 0
- O 0
independent O 0
prostate B-Disease 0
cancer I-Disease 0
in O 0
an O 0
open O 0
- O 0
label O 0
trial O 0
of O 0
oral O 0
thalidomide B-Chemical 0
underwent O 0
neurologic O 0
examinations O 0
and O 0
nerve O 0
conduction O 0
studies O 0
( O 0
NCS O 0
) O 0
prior O 0
to O 0
and O 0
at O 0
3 O 0
- O 0
month O 0
intervals O 0
during O 0
treatment O 0
. O 0

NCS O 0
included O 0
recording O 0
of O 0
sensory O 0
nerve O 0
action O 0
potentials O 0
( O 0
SNAPs O 0
) O 0
from O 0
median O 0
, O 0
radial O 0
, O 0
ulnar O 0
, O 0
and O 0
sural O 0
nerves O 0
. O 0

SNAP O 0
amplitudes O 0
for O 0
each O 0
nerve O 0
were O 0
expressed O 0
as O 0
the O 0
percentage O 0
of O 0
its O 0
baseline O 0
, O 0
and O 0
the O 0
mean O 0
of O 0
the O 0
four O 0
was O 0
termed O 0
the O 0
SNAP O 0
index O 0
. O 0

A O 0
40 O 0
% O 0
decline O 0
in O 0
the O 0
SNAP O 0
index O 0
was O 0
considered O 0
clinically O 0
significant O 0
. O 0

Thalidomide B-Chemical 0
was O 0
discontinued O 0
in O 0
55 O 0
patients O 0
for O 0
lack O 0
of O 0
therapeutic O 0
response O 0
. O 0

Of O 0
67 O 0
patients O 0
initially O 0
enrolled O 0
, O 0
24 O 0
remained O 0
on O 0
thalidomide B-Chemical 0
for O 0
3 O 0
months O 0
, O 0
8 O 0
remained O 0
at O 0
6 O 0
months O 0
, O 0
and O 0
3 O 0
remained O 0
at O 0
9 O 0
months O 0
. O 0

Six O 0
patients O 0
developed O 0
neuropathy B-Disease 0
. O 0

Clinical O 0
symptoms O 0
and O 0
a O 0
decline O 0
in O 0
the O 0
SNAP O 0
index O 0
occurred O 0
concurrently O 0
. O 0

Older O 0
age O 0
and O 0
cumulative O 0
dose O 0
were O 0
possible O 0
contributing O 0
factors O 0
. O 0

Neuropathy B-Disease 0
may O 0
thus O 0
be O 0
a O 0
common O 0
complication O 0
of O 0
thalidomide B-Chemical 0
in O 0
older O 0
patients O 0
. O 0

The O 0
SNAP O 0
index O 0
can O 0
be O 0
used O 0
to O 0
monitor O 0
peripheral B-Disease 0
neuropathy I-Disease 0
, O 0
but O 0
not O 0
for O 0
early O 0
detection O 0
. O 0

Overexpression O 0
of O 0
copper B-Chemical 0
/ O 0
zinc B-Chemical 0
- O 0
superoxide B-Chemical 0
dismutase O 0
protects O 0
from O 0
kanamycin B-Chemical 0
- O 0
induced O 0
hearing B-Disease 0
loss I-Disease 0
. O 0

The O 0
participation O 0
of O 0
reactive O 0
oxygen B-Chemical 0
species O 0
in O 0
aminoglycoside B-Chemical 0
- O 0
induced O 0
ototoxicity B-Disease 0
has O 0
been O 0
deduced O 0
from O 0
observations O 0
that O 0
aminoglycoside B-Chemical 0
- O 0
iron B-Chemical 0
complexes O 0
catalyze O 0
the O 0
formation O 0
of O 0
superoxide B-Chemical 0
radicals O 0
in O 0
vitro O 0
and O 0
that O 0
antioxidants O 0
attenuate O 0
ototoxicity B-Disease 0
in O 0
vivo O 0
. O 0

We O 0
therefore O 0
hypothesized O 0
that O 0
overexpression O 0
of O 0
Cu B-Chemical 0
/ O 0
Zn B-Chemical 0
- O 0
superoxide B-Chemical 0
dismutase O 0
( O 0
h O 0
- O 0
SOD1 O 0
) O 0
should O 0
protect O 0
transgenic O 0
mice O 0
from O 0
ototoxicity B-Disease 0
. O 0

Immunocytochemistry O 0
confirmed O 0
expression O 0
of O 0
h O 0
- O 0
SOD1 O 0
in O 0
inner O 0
ear O 0
tissues O 0
of O 0
transgenic O 0
C57BL O 0
/ O 0
6 O 0
- O 0
TgN O 0
[ O 0
SOD1 O 0
] O 0
3Cje O 0
mice O 0
. O 0

Transgenic O 0
and O 0
nontransgenic O 0
littermates O 0
received O 0
kanamycin B-Chemical 0
( O 0
400 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
/ O 0
day O 0
) O 0
for O 0
10 O 0
days O 0
beginning O 0
on O 0
day O 0
10 O 0
after O 0
birth O 0
. O 0

Auditory O 0
thresholds O 0
were O 0
tested O 0
by O 0
evoked O 0
auditory O 0
brain O 0
stem O 0
responses O 0
at O 0
1 O 0
month O 0
after O 0
birth O 0
. O 0

In O 0
nontransgenic O 0
animals O 0
, O 0
the O 0
threshold O 0
in O 0
the O 0
kanamycin B-Chemical 0
- O 0
treated O 0
group O 0
was O 0
45 O 0
- O 0
50 O 0
dB O 0
higher O 0
than O 0
in O 0
saline O 0
- O 0
injected O 0
controls O 0
. O 0

In O 0
the O 0
transgenic O 0
group O 0
, O 0
kanamycin B-Chemical 0
increased O 0
the O 0
threshold O 0
by O 0
only O 0
15 O 0
dB O 0
over O 0
the O 0
respective O 0
controls O 0
. O 0

The O 0
effects O 0
were O 0
similar O 0
at O 0
12 O 0
and O 0
24 O 0
kHz O 0
. O 0

The O 0
protection O 0
by O 0
overexpression O 0
of O 0
superoxide B-Chemical 0
dismutase O 0
supports O 0
the O 0
hypothesis O 0
that O 0
oxidant O 0
stress O 0
plays O 0
a O 0
significant O 0
role O 0
in O 0
aminoglycoside B-Chemical 0
- O 0
induced O 0
ototoxicity B-Disease 0
. O 0

The O 0
results O 0
also O 0
suggest O 0
transgenic O 0
animals O 0
as O 0
suitable O 0
models O 0
to O 0
investigate O 0
the O 0
underlying O 0
mechanisms O 0
and O 0
possible O 0
strategies O 0
for O 0
prevention O 0
. O 0

Fatty B-Disease 0
liver I-Disease 0
induced O 0
by O 0
tetracycline B-Chemical 0
in O 0
the O 0
rat O 0
. O 0

Dose O 0
- O 0
response O 0
relationships O 0
and O 0
effect O 0
of O 0
sex O 0
. O 0

Dose O 0
- O 0
response O 0
relationships O 0
, O 0
biochemical O 0
mechanisms O 0
, O 0
and O 0
sex O 0
differences O 0
in O 0
the O 0
experimental O 0
fatty B-Disease 0
liver I-Disease 0
induced O 0
by O 0
tetracycline B-Chemical 0
were O 0
studied O 0
in O 0
the O 0
intact O 0
rat O 0
and O 0
with O 0
the O 0
isolated O 0
perfused O 0
rat O 0
liver O 0
in O 0
vitro O 0
. O 0

In O 0
the O 0
intact O 0
male O 0
and O 0
female O 0
rat O 0
, O 0
no O 0
direct O 0
relationship O 0
was O 0
observed O 0
between O 0
dose O 0
of O 0
tetracycline B-Chemical 0
and O 0
hepatic O 0
accumulation O 0
of O 0
triglyceride B-Chemical 0
. O 0

With O 0
provision O 0
of O 0
adequate O 0
oleic B-Chemical 0
acid I-Chemical 0
as O 0
a O 0
substrate O 0
for O 0
the O 0
isolated O 0
perfused O 0
liver O 0
, O 0
a O 0
direct O 0
relationship O 0
was O 0
observed O 0
between O 0
dose O 0
of O 0
tetracycline B-Chemical 0
and O 0
both O 0
accumulation O 0
of O 0
triglyceride B-Chemical 0
in O 0
the O 0
liver O 0
and O 0
depression B-Disease 0
of O 0
output O 0
of O 0
triglyceride B-Chemical 0
by O 0
livers O 0
from O 0
male O 0
and O 0
female O 0
rats O 0
. O 0

Marked O 0
differences O 0
were O 0
observed O 0
between O 0
female O 0
and O 0
male O 0
rats O 0
with O 0
regard O 0
to O 0
base O 0
line O 0
( O 0
control O 0
) O 0
hepatic O 0
concentration O 0
of O 0
triglyceride B-Chemical 0
and O 0
output O 0
of O 0
triglyceride B-Chemical 0
. O 0

Accumulation O 0
of O 0
hepatic O 0
triglyceride B-Chemical 0
, O 0
as O 0
a O 0
per O 0
cent O 0
of O 0
control O 0
values O 0
, O 0
in O 0
response O 0
to O 0
graded O 0
doses O 0
of O 0
tetracycline B-Chemical 0
, O 0
did O 0
not O 0
differ O 0
significantly O 0
between O 0
male O 0
, O 0
female O 0
and O 0
pregnant O 0
rat O 0
livers O 0
. O 0

However O 0
, O 0
livers O 0
from O 0
female O 0
, O 0
and O 0
especially O 0
pregnant O 0
female O 0
rats O 0
, O 0
were O 0
strikingly O 0
resistant O 0
to O 0
the O 0
effects O 0
of O 0
tetracycline B-Chemical 0
on O 0
depression B-Disease 0
of O 0
output O 0
of O 0
triglyceride B-Chemical 0
under O 0
these O 0
experimental O 0
conditions O 0
. O 0

These O 0
differences O 0
between O 0
the O 0
sexes O 0
could O 0
not O 0
be O 0
related O 0
to O 0
altered O 0
disposition O 0
of O 0
tetracycline B-Chemical 0
or O 0
altered O 0
uptake O 0
of O 0
oleic B-Chemical 0
acid I-Chemical 0
. O 0

Depressed O 0
hepatic O 0
secretion O 0
of O 0
triglyceride B-Chemical 0
accounted O 0
only O 0
for O 0
30 O 0
to O 0
50 O 0
% O 0
of O 0
accumulated O 0
hepatic O 0
triglyceride B-Chemical 0
, O 0
indicating O 0
that O 0
additional O 0
mechanisms O 0
must O 0
be O 0
involved O 0
in O 0
the O 0
production O 0
of O 0
the O 0
triglyceride B-Chemical 0
- O 0
rich O 0
fatty B-Disease 0
liver I-Disease 0
in O 0
response O 0
to O 0
tetracycline B-Chemical 0
. O 0

Prednisone B-Chemical 0
induces O 0
anxiety B-Disease 0
and O 0
glial O 0
cerebral O 0
changes O 0
in O 0
rats O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
assess O 0
whether O 0
prednisone B-Chemical 0
( O 0
PDN B-Chemical 0
) O 0
produces O 0
anxiety B-Disease 0
and O 0
/ O 0
or O 0
cerebral O 0
glial O 0
changes O 0
in O 0
rats O 0
. O 0

METHODS O 0
: O 0
Male O 0
Wistar O 0
rats O 0
were O 0
studied O 0
and O 0
3 O 0
groups O 0
were O 0
formed O 0
( O 0
8 O 0
rats O 0
per O 0
group O 0
) O 0
. O 0

The O 0
moderate O 0
- O 0
dose O 0
group O 0
received O 0
5 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
PDN B-Chemical 0
released O 0
from O 0
a O 0
subcutaneous O 0
implant O 0
. O 0

In O 0
the O 0
high O 0
- O 0
dose O 0
group O 0
, O 0
implants O 0
containing O 0
PDN B-Chemical 0
equivalent O 0
to O 0
60 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
were O 0
applied O 0
. O 0

In O 0
the O 0
control O 0
group O 0
implants O 0
contained O 0
no O 0
PDN B-Chemical 0
. O 0

Anxiety B-Disease 0
was O 0
assessed O 0
using O 0
an O 0
open O 0
field O 0
and O 0
elevated O 0
plus O 0
- O 0
maze O 0
devices O 0
. O 0

The O 0
number O 0
of O 0
cells O 0
and O 0
cytoplasmic O 0
transformation O 0
of O 0
astrocytes O 0
and O 0
microglia O 0
cells O 0
were O 0
assessed O 0
by O 0
immunohistochemical O 0
analyses O 0
. O 0

RESULTS O 0
: O 0
Anxiety B-Disease 0
was O 0
documented O 0
in O 0
both O 0
groups O 0
of O 0
PDN B-Chemical 0
treated O 0
rats O 0
compared O 0
with O 0
controls O 0
. O 0

The O 0
magnitude O 0
of O 0
transformation O 0
of O 0
the O 0
microglia O 0
assessed O 0
by O 0
the O 0
number O 0
of O 0
intersections O 0
was O 0
significantly O 0
higher O 0
in O 0
the O 0
PDN B-Chemical 0
groups O 0
than O 0
in O 0
controls O 0
in O 0
the O 0
prefrontal O 0
cortex O 0
( O 0
moderate O 0
- O 0
dose O 0
, O 0
24 O 0
. O 0
1 O 0
; O 0
high O 0
- O 0
dose O 0
, O 0
23 O 0
. O 0
6 O 0
; O 0
controls O 0
18 O 0
. O 0
7 O 0
; O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
and O 0
striatum O 0
( O 0
moderate O 0
- O 0
dose O 0
25 O 0
. O 0
6 O 0
; O 0
high O 0
- O 0
dose O 0
26 O 0
. O 0
3 O 0
; O 0
controls O 0
18 O 0
. O 0
9 O 0
; O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
, O 0
but O 0
not O 0
in O 0
hippocampus O 0
. O 0

The O 0
number O 0
of O 0
stained O 0
microglia O 0
cells O 0
was O 0
significantly O 0
higher O 0
in O 0
the O 0
PDN B-Chemical 0
treated O 0
groups O 0
in O 0
the O 0
prefrontal O 0
cortex O 0
than O 0
in O 0
controls O 0
( O 0
moderate O 0
- O 0
dose O 0
, O 0
29 O 0
. O 0
1 O 0
; O 0
high O 0
- O 0
dose O 0
, O 0
28 O 0
. O 0
4 O 0
; O 0
control O 0
, O 0
17 O 0
. O 0
7 O 0
cells O 0
per O 0
field O 0
; O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Stained O 0
microglia O 0
cells O 0
were O 0
significantly O 0
more O 0
numerous O 0
striatum O 0
and O 0
hippocampus O 0
in O 0
the O 0
high O 0
- O 0
dose O 0
group O 0
compared O 0
to O 0
controls O 0
. O 0

CONCLUSION O 0
: O 0
Subacute O 0
exposure O 0
to O 0
PDN B-Chemical 0
induced O 0
anxiety B-Disease 0
and O 0
reactivity O 0
of O 0
microglia O 0
. O 0

The O 0
relevance O 0
of O 0
these O 0
features O 0
for O 0
patients O 0
using O 0
PDN B-Chemical 0
remains O 0
to O 0
be O 0
elucidated O 0
. O 0

Phase O 0
II O 0
study O 0
of O 0
carboplatin B-Chemical 0
and O 0
liposomal O 0
doxorubicin B-Chemical 0
in O 0
patients O 0
with O 0
recurrent O 0
squamous B-Disease 0
cell I-Disease 0
carcinoma I-Disease 0
of I-Disease 0
the I-Disease 0
cervix I-Disease 0
. O 0

BACKGROUND O 0
: O 0
The O 0
activity O 0
of O 0
the O 0
combination O 0
of O 0
carboplatin B-Chemical 0
and O 0
liposomal O 0
doxorubicin B-Chemical 0
was O 0
tested O 0
in O 0
a O 0
Phase O 0
II O 0
study O 0
of O 0
patients O 0
with O 0
recurrent O 0
cervical B-Disease 0
carcinoma I-Disease 0
. O 0

METHODS O 0
: O 0
The O 0
combination O 0
of O 0
carboplatin B-Chemical 0
( O 0
area O 0
under O 0
the O 0
concentration O 0
curve O 0
[ O 0
AUC O 0
] O 0
, O 0
5 O 0
) O 0
and O 0
liposomal O 0
doxorubicin B-Chemical 0
( O 0
Doxil B-Chemical 0
; O 0
starting O 0
dose O 0
, O 0
40 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
) O 0
was O 0
administered O 0
intravenously O 0
every O 0
28 O 0
days O 0
to O 0
37 O 0
patients O 0
with O 0
recurrent O 0
squamous B-Disease 0
cell I-Disease 0
cervical I-Disease 0
carcinoma I-Disease 0
to O 0
determine O 0
antitumor O 0
activity O 0
and O 0
toxicity B-Disease 0
profile O 0
. O 0

RESULTS O 0
: O 0
Twenty O 0
- O 0
nine O 0
patients O 0
were O 0
assessable O 0
for O 0
response O 0
, O 0
and O 0
35 O 0
patients O 0
were O 0
assessable O 0
for O 0
toxicity B-Disease 0
. O 0

The O 0
overall O 0
response O 0
rate O 0
was O 0
38 O 0
% O 0
, O 0
the O 0
median O 0
time O 0
to O 0
response O 0
was O 0
10 O 0
weeks O 0
, O 0
the O 0
median O 0
duration O 0
of O 0
response O 0
was O 0
26 O 0
weeks O 0
, O 0
and O 0
the O 0
median O 0
survival O 0
was O 0
37 O 0
weeks O 0
. O 0

The O 0
main O 0
toxic O 0
effect O 0
was O 0
myelosuppression B-Disease 0
, O 0
with O 0
Grade O 0
3 O 0
and O 0
4 O 0
neutropenia B-Disease 0
in O 0
16 O 0
patients O 0
, O 0
anemia B-Disease 0
in O 0
12 O 0
patients O 0
, O 0
thrombocytopenia B-Disease 0
in O 0
11 O 0
patients O 0
, O 0
and O 0
neutropenic B-Disease 0
fever I-Disease 0
in O 0
3 O 0
patients O 0
. O 0

Four O 0
patients O 0
had O 0
five O 0
infusion O 0
- O 0
related O 0
reactions O 0
during O 0
the O 0
infusion O 0
of O 0
liposomal O 0
doxorubicin B-Chemical 0
, O 0
leading O 0
to O 0
treatment O 0
discontinuation O 0
in O 0
three O 0
patients O 0
. O 0

Grade O 0
> O 0
or O 0
= O 0
2 O 0
nonhematologic O 0
toxicity B-Disease 0
included O 0
nausea B-Disease 0
in O 0
17 O 0
patients O 0
, O 0
emesis B-Disease 0
in O 0
14 O 0
patients O 0
, O 0
fatigue B-Disease 0
in O 0
9 O 0
patients O 0
, O 0
mucositis B-Disease 0
and O 0
/ O 0
or O 0
stomatitis B-Disease 0
in O 0
8 O 0
patients O 0
, O 0
constipation B-Disease 0
in O 0
6 O 0
patients O 0
, O 0
weight B-Disease 0
loss I-Disease 0
in O 0
5 O 0
patients O 0
, O 0
hand B-Disease 0
- I-Disease 0
foot I-Disease 0
syndrome I-Disease 0
in O 0
2 O 0
patients O 0
, O 0
and O 0
skin B-Disease 0
reactions I-Disease 0
in O 0
3 O 0
patients O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
combination O 0
of O 0
carboplatin B-Chemical 0
and O 0
liposomal O 0
doxorubicin B-Chemical 0
has O 0
modest O 0
activity O 0
in O 0
patients O 0
with O 0
recurrent O 0
cervical B-Disease 0
carcinoma I-Disease 0
. O 0

Antimicrobial O 0
- O 0
induced O 0
mania B-Disease 0
( O 0
antibiomania B-Disease 0
) O 0
: O 0
a O 0
review O 0
of O 0
spontaneous O 0
reports O 0
. O 0

The O 0
authors O 0
reviewed O 0
reported O 0
cases O 0
of O 0
antibiotic O 0
- O 0
induced O 0
manic B-Disease 0
episodes O 0
by O 0
means O 0
of O 0
a O 0
MEDLINE O 0
and O 0
PsychLit O 0
search O 0
for O 0
reports O 0
of O 0
antibiotic O 0
- O 0
induced O 0
mania B-Disease 0
. O 0

Unpublished O 0
reports O 0
were O 0
requested O 0
from O 0
the O 0
World O 0
Health O 0
Organization O 0
( O 0
WHO O 0
) O 0
and O 0
the O 0
Food O 0
and O 0
Drug O 0
Administration O 0
( O 0
FDA O 0
) O 0
. O 0

Twenty O 0
- O 0
one O 0
reports O 0
of O 0
antimicrobial O 0
- O 0
induced O 0
mania B-Disease 0
were O 0
found O 0
in O 0
the O 0
literature O 0
. O 0

There O 0
were O 0
6 O 0
cases O 0
implicating O 0
clarithromycin B-Chemical 0
, O 0
13 O 0
implicating O 0
isoniazid B-Chemical 0
, O 0
and O 0
1 O 0
case O 0
each O 0
implicating O 0
erythromycin B-Chemical 0
and O 0
amoxicillin B-Chemical 0
. O 0

The O 0
WHO O 0
reported O 0
82 O 0
cases O 0
. O 0

Of O 0
these O 0
, O 0
clarithromycin B-Chemical 0
was O 0
implicated O 0
in O 0
23 O 0
( O 0
27 O 0
. O 0
6 O 0
% O 0
) O 0
cases O 0
, O 0
ciprofloxacin B-Chemical 0
in O 0
12 O 0
( O 0
14 O 0
. O 0
4 O 0
% O 0
) O 0
cases O 0
, O 0
and O 0
ofloxacin B-Chemical 0
in O 0
10 O 0
( O 0
12 O 0
% O 0
) O 0
cases O 0
. O 0

Cotrimoxazole B-Chemical 0
, O 0
metronidazole B-Chemical 0
, O 0
and O 0
erythromycin B-Chemical 0
were O 0
involved O 0
in O 0
15 O 0
reported O 0
manic B-Disease 0
episodes O 0
. O 0

Cases O 0
reported O 0
by O 0
the O 0
FDA O 0
showed O 0
clarithromycin B-Chemical 0
and O 0
ciprofloxacin B-Chemical 0
to O 0
be O 0
the O 0
most O 0
frequently O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
mania B-Disease 0
. O 0

Statistical O 0
analysis O 0
of O 0
the O 0
data O 0
would O 0
not O 0
have O 0
demonstrated O 0
a O 0
significant O 0
statistical O 0
correlative O 0
risk O 0
and O 0
was O 0
therefore O 0
not O 0
undertaken O 0
. O 0

Patients O 0
have O 0
an O 0
increased O 0
risk O 0
of O 0
developing O 0
mania B-Disease 0
while O 0
being O 0
treated O 0
with O 0
antimicrobials O 0
. O 0

Although O 0
this O 0
is O 0
not O 0
a O 0
statistically O 0
significant O 0
risk O 0
, O 0
physicians O 0
must O 0
be O 0
aware O 0
of O 0
the O 0
effect O 0
and O 0
reversibility O 0
. O 0

Further O 0
research O 0
clearly O 0
is O 0
required O 0
to O 0
determine O 0
the O 0
incidence O 0
of O 0
antimicrobial O 0
- O 0
induced O 0
mania B-Disease 0
, O 0
the O 0
relative O 0
risk O 0
factors O 0
of O 0
developing O 0
an O 0
antimicrobial O 0
- O 0
induced O 0
manic B-Disease 0
episode O 0
among O 0
various O 0
demographic O 0
populations O 0
, O 0
and O 0
the O 0
incidence O 0
of O 0
patients O 0
who O 0
continue O 0
to O 0
have O 0
persistent O 0
affective O 0
disorders O 0
once O 0
the O 0
initial O 0
episode O 0
, O 0
which O 0
occurs O 0
while O 0
the O 0
patient O 0
is O 0
taking O 0
antibiotics O 0
, O 0
subsides O 0
. O 0

The O 0
authors O 0
elected O 0
to O 0
name O 0
this O 0
syndrome O 0
" O 0
antibiomania B-Disease 0
. O 0
" O 0

Levodopa B-Chemical 0
- O 0
induced O 0
ocular B-Disease 0
dyskinesias I-Disease 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

Levodopa B-Chemical 0
- O 0
induced O 0
ocular B-Disease 0
dyskinesias I-Disease 0
are O 0
very O 0
uncommon O 0
. O 0

Usually O 0
they O 0
occur O 0
simultaneously O 0
with O 0
limb O 0
peak O 0
- O 0
dose O 0
choreatic B-Disease 0
dyskinesias I-Disease 0
. O 0

We O 0
report O 0
on O 0
a O 0
patient O 0
with O 0
leftward O 0
and O 0
upward O 0
deviations O 0
of O 0
gaze O 0
during O 0
the O 0
peak O 0
effect O 0
of O 0
levodopa B-Chemical 0
, O 0
and O 0
hypothesize O 0
that O 0
a O 0
severe O 0
dopaminergic O 0
denervation O 0
in O 0
the O 0
caudate O 0
nucleus O 0
is O 0
needed O 0
for O 0
the O 0
appearance O 0
of O 0
these O 0
levodopa B-Chemical 0
- O 0
induce O 0
ocular B-Disease 0
dyskinesias I-Disease 0
. O 0

A O 0
comparison O 0
of O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
with O 0
diclofenac B-Chemical 0
for O 0
the O 0
treatment O 0
of O 0
primary O 0
dysmenorrhea B-Disease 0
: O 0
an O 0
open O 0
, O 0
randomized O 0
, O 0
cross O 0
- O 0
over O 0
trial O 0
. O 0

Primary O 0
dysmenorrhea B-Disease 0
is O 0
a O 0
syndrome O 0
characterized O 0
by O 0
painful O 0
uterine O 0
contractility O 0
caused O 0
by O 0
a O 0
hypersecretion O 0
of O 0
endometrial O 0
prostaglandins B-Chemical 0
; O 0
non O 0
- O 0
steroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
are O 0
the O 0
first O 0
choice O 0
for O 0
its O 0
treatment O 0
. O 0

However O 0
, O 0
in O 0
vivo O 0
and O 0
in O 0
vitro O 0
studies O 0
have O 0
demonstrated O 0
that O 0
myometrial O 0
cells O 0
are O 0
also O 0
targets O 0
of O 0
the O 0
relaxant O 0
effects O 0
of O 0
nitric B-Chemical 0
oxide I-Chemical 0
( O 0
NO B-Chemical 0
) O 0
. O 0

The O 0
aim O 0
of O 0
the O 0
present O 0
study O 0
was O 0
to O 0
determine O 0
the O 0
efficacy O 0
of O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
( O 0
GTN B-Chemical 0
) O 0
, O 0
an O 0
NO B-Chemical 0
donor O 0
, O 0
in O 0
the O 0
resolution O 0
of O 0
primary O 0
dysmenorrhea B-Disease 0
in O 0
comparison O 0
with O 0
diclofenac B-Chemical 0
( O 0
DCF B-Chemical 0
) O 0
. O 0

A O 0
total O 0
of O 0
24 O 0
patients O 0
with O 0
the O 0
diagnosis O 0
of O 0
severe O 0
primary O 0
dysmenorrhea B-Disease 0
were O 0
studied O 0
during O 0
two O 0
consecutive O 0
menstrual O 0
cycles O 0
. O 0

In O 0
an O 0
open O 0
, O 0
cross O 0
- O 0
over O 0
, O 0
controlled O 0
design O 0
, O 0
patients O 0
were O 0
randomized O 0
to O 0
receive O 0
either O 0
DCF B-Chemical 0
per O 0
os O 0
or O 0
GTN B-Chemical 0
patches O 0
the O 0
first O 0
days O 0
of O 0
menses O 0
, O 0
when O 0
menstrual O 0
cramps O 0
became O 0
unendurable O 0
. O 0

In O 0
the O 0
subsequent O 0
cycle O 0
the O 0
other O 0
treatment O 0
was O 0
used O 0
. O 0

Patients O 0
received O 0
up O 0
to O 0
3 O 0
doses O 0
/ O 0
day O 0
of O 0
50 O 0
mg O 0
DCF B-Chemical 0
or O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
24 O 0
h O 0
transdermal O 0
GTN B-Chemical 0
for O 0
the O 0
first O 0
3 O 0
days O 0
of O 0
the O 0
cycle O 0
, O 0
according O 0
to O 0
their O 0
needs O 0
. O 0

The O 0
participants O 0
recorded O 0
menstrual O 0
symptoms O 0
and O 0
possible O 0
side O 0
- O 0
effects O 0
at O 0
different O 0
times O 0
( O 0
0 O 0
, O 0
30 O 0
, O 0
60 O 0
, O 0
120 O 0
minutes O 0
) O 0
after O 0
the O 0
first O 0
dose O 0
of O 0
medication O 0
on O 0
the O 0
first O 0
day O 0
of O 0
the O 0
cycle O 0
, O 0
with O 0
both O 0
drugs O 0
. O 0

The O 0
difference O 0
in O 0
pain B-Disease 0
intensity O 0
score O 0
( O 0
DPI O 0
) O 0
was O 0
the O 0
main O 0
outcome O 0
variable O 0
. O 0

Both O 0
treatments O 0
significantly O 0
reduced O 0
DPI O 0
by O 0
the O 0
30th O 0
minute O 0
( O 0
GTN B-Chemical 0
, O 0
- O 0
12 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
17 O 0
. O 0
9 O 0
; O 0
DCF B-Chemical 0
, O 0
- O 0
18 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
16 O 0
. O 0
6 O 0
) O 0
. O 0

However O 0
, O 0
DCF B-Chemical 0
continued O 0
to O 0
be O 0
effective O 0
in O 0
reducing O 0
pelvic B-Disease 0
pain I-Disease 0
for O 0
two O 0
hours O 0
, O 0
whereas O 0
GTN B-Chemical 0
scores O 0
remained O 0
more O 0
or O 0
less O 0
stable O 0
after O 0
30 O 0
min O 0
and O 0
significantly O 0
higher O 0
than O 0
those O 0
for O 0
DFC O 0
( O 0
after O 0
one O 0
hour O 0
: O 0
GTN B-Chemical 0
, O 0
- O 0
12 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
17 O 0
. O 0
9 O 0
; O 0
DFC O 0
, O 0
- O 0
18 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
16 O 0
. O 0
6 O 0
and O 0
after O 0
two O 0
hours O 0
: O 0
GTN B-Chemical 0
, O 0
- O 0
23 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
20 O 0
. O 0
5 O 0
; O 0
DFC O 0
, O 0
- O 0
59 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
17 O 0
. O 0
9 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
0001 O 0
) O 0
. O 0

Low B-Disease 0
back I-Disease 0
pain I-Disease 0
was O 0
also O 0
relieved O 0
by O 0
both O 0
drugs O 0
. O 0

Headache B-Disease 0
was O 0
significantly O 0
increased O 0
by O 0
GTN B-Chemical 0
but O 0
not O 0
by O 0
DCF B-Chemical 0
. O 0

Eight O 0
patients O 0
stopped O 0
using O 0
GTN B-Chemical 0
because O 0
headache B-Disease 0
- O 0
- O 0
attributed O 0
to O 0
its O 0
use O 0
- O 0
- O 0
became O 0
intolerable O 0
. O 0

These O 0
findings O 0
indicate O 0
that O 0
GTN B-Chemical 0
has O 0
a O 0
reduced O 0
efficacy O 0
and O 0
tolerability O 0
by O 0
comparison O 0
with O 0
DCF B-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
primary O 0
dysmenorrhea B-Disease 0
. O 0

Temocapril B-Chemical 0
, O 0
a O 0
long O 0
- O 0
acting O 0
non O 0
- O 0
SH O 0
group O 0
angiotensin B-Chemical 0
converting O 0
enzyme O 0
inhibitor O 0
, O 0
modulates O 0
glomerular B-Disease 0
injury I-Disease 0
in O 0
chronic O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
nephrosis B-Disease 0
. O 0

The O 0
purpose O 0
of O 0
the O 0
present O 0
study O 0
was O 0
to O 0
determine O 0
whether O 0
chronic O 0
administration O 0
of O 0
temocapril B-Chemical 0
, O 0
a O 0
long O 0
- O 0
acting O 0
non O 0
- O 0
SH O 0
group O 0
angiotensin B-Chemical 0
converting O 0
enzyme O 0
( O 0
ACE O 0
) O 0
inhibitor O 0
, O 0
reduced O 0
proteinuria B-Disease 0
, O 0
inhibited O 0
glomerular O 0
hypertrophy B-Disease 0
and O 0
prevented O 0
glomerulosclerosis B-Disease 0
in O 0
chronic O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
( O 0
PAN B-Chemical 0
) O 0
- O 0
induced O 0
nephrotic B-Disease 0
rats O 0
. O 0

Nephrosis B-Disease 0
was O 0
induced O 0
by O 0
injection O 0
of O 0
PAN B-Chemical 0
( O 0
15mg O 0
/ O 0
100g O 0
body O 0
weight O 0
) O 0
in O 0
male O 0
Sprague O 0
- O 0
Dawley O 0
( O 0
SD O 0
) O 0
rats O 0
. O 0

Four O 0
groups O 0
were O 0
used O 0
, O 0
i O 0
) O 0
the O 0
PAN B-Chemical 0
group O 0
( O 0
14 O 0
) O 0
, O 0
ii O 0
) O 0
PAN B-Chemical 0
/ O 0
temocapril B-Chemical 0
( O 0
13 O 0
) O 0
, O 0
iii O 0
) O 0
temocapril B-Chemical 0
( O 0
14 O 0
) O 0
and O 0
iv O 0
) O 0
untreated O 0
controls O 0
( O 0
15 O 0
) O 0
. O 0

Temocapril B-Chemical 0
( O 0
8 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
) O 0
was O 0
administered O 0
to O 0
the O 0
rats O 0
which O 0
were O 0
killed O 0
at O 0
weeks O 0
4 O 0
, O 0
14 O 0
or O 0
20 O 0
. O 0

At O 0
each O 0
time O 0
point O 0
, O 0
systolic O 0
blood O 0
pressure O 0
( O 0
BP O 0
) O 0
, O 0
urinary O 0
protein O 0
excretion O 0
and O 0
renal O 0
histopathological O 0
findings O 0
were O 0
evaluated O 0
, O 0
and O 0
morphometric O 0
image O 0
analysis O 0
was O 0
done O 0
. O 0

Systolic O 0
BP O 0
in O 0
the O 0
PAN B-Chemical 0
group O 0
was O 0
significantly O 0
high O 0
at O 0
4 O 0
, O 0
14 O 0
and O 0
20 O 0
weeks O 0
, O 0
but O 0
was O 0
normal O 0
in O 0
the O 0
PAN B-Chemical 0
/ O 0
temocapril B-Chemical 0
group O 0
. O 0

Urinary O 0
protein O 0
excretion O 0
in O 0
the O 0
PAN B-Chemical 0
group O 0
increased O 0
significantly O 0
, O 0
peaking O 0
at O 0
8 O 0
days O 0
, O 0
then O 0
decreased O 0
at O 0
4 O 0
weeks O 0
, O 0
but O 0
rose O 0
again O 0
significantly O 0
at O 0
14 O 0
and O 0
20 O 0
weeks O 0
. O 0

Temocapril B-Chemical 0
did O 0
not O 0
attenuate O 0
proteinuria B-Disease 0
at O 0
8 O 0
days O 0
, O 0
but O 0
it O 0
did O 0
markedly O 0
lower O 0
it O 0
from O 0
weeks O 0
4 O 0
to O 0
20 O 0
. O 0

The O 0
glomerulosclerosis B-Disease 0
index O 0
( O 0
GSI O 0
) O 0
was O 0
6 O 0
. O 0
21 O 0
% O 0
at O 0
4 O 0
weeks O 0
and O 0
respectively O 0
25 O 0
. O 0
35 O 0
% O 0
and O 0
30 O 0
. O 0
49 O 0
% O 0
at O 0
14 O 0
and O 0
20 O 0
weeks O 0
in O 0
the O 0
PAN B-Chemical 0
group O 0
. O 0

There O 0
was O 0
a O 0
significant O 0
correlation O 0
between O 0
urinary O 0
protein O 0
excretion O 0
and O 0
GSI O 0
( O 0
r O 0
= O 0
0 O 0
. O 0
808 O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
0001 O 0
) O 0
. O 0

The O 0
ratio O 0
of O 0
glomerular O 0
tuft O 0
area O 0
to O 0
the O 0
area O 0
of O 0
Bowman O 0
' O 0
s O 0
capsules O 0
( O 0
GT O 0
/ O 0
BC O 0
) O 0
in O 0
the O 0
PAN B-Chemical 0
group O 0
was O 0
significantly O 0
increased O 0
, O 0
but O 0
it O 0
was O 0
significantly O 0
lower O 0
in O 0
the O 0
PAN B-Chemical 0
/ O 0
temocapril B-Chemical 0
group O 0
. O 0

It O 0
appears O 0
that O 0
temocapril B-Chemical 0
was O 0
effective O 0
in O 0
retarding O 0
renal O 0
progression O 0
and O 0
protected O 0
renal O 0
function O 0
in O 0
PAN B-Chemical 0
neprotic B-Disease 0
rats O 0
. O 0

Pulmonary B-Disease 0
hypertension I-Disease 0
after O 0
ibuprofen B-Chemical 0
prophylaxis O 0
in O 0
very O 0
preterm O 0
infants O 0
. O 0

We O 0
report O 0
three O 0
cases O 0
of O 0
severe O 0
hypoxaemia B-Disease 0
after O 0
ibuprofen B-Chemical 0
administration O 0
during O 0
a O 0
randomised O 0
controlled O 0
trial O 0
of O 0
prophylactic O 0
treatment O 0
of O 0
patent B-Disease 0
ductus I-Disease 0
arteriosus I-Disease 0
with O 0
ibuprofen B-Chemical 0
in O 0
premature O 0
infants O 0
born O 0
at O 0
less O 0
than O 0
28 O 0
weeks O 0
of O 0
gestation O 0
. O 0

Echocardiography O 0
showed O 0
severely O 0
decreased O 0
pulmonary O 0
blood O 0
flow O 0
. O 0

Hypoxaemia B-Disease 0
resolved O 0
quickly O 0
on O 0
inhaled O 0
nitric B-Chemical 0
oxide I-Chemical 0
therapy O 0
. O 0

We O 0
suggest O 0
that O 0
investigators O 0
involved O 0
in O 0
similar O 0
trials O 0
pay O 0
close O 0
attention O 0
to O 0
pulmonary O 0
pressure O 0
if O 0
hypoxaemia B-Disease 0
occurs O 0
after O 0
prophylactic O 0
administration O 0
of O 0
ibuprofen B-Chemical 0
. O 0

Hyponatremia B-Disease 0
and O 0
syndrome B-Disease 0
of I-Disease 0
inappropriate I-Disease 0
anti I-Disease 0
- I-Disease 0
diuretic I-Disease 0
hormone I-Disease 0
reported O 0
with O 0
the O 0
use O 0
of O 0
Vincristine B-Chemical 0
: O 0
an O 0
over O 0
- O 0
representation O 0
of O 0
Asians O 0
? O 0

PURPOSE O 0
: O 0
This O 0
retrospective O 0
study O 0
used O 0
a O 0
pharmaceutical O 0
company O 0
' O 0
s O 0
global O 0
safety O 0
database O 0
to O 0
determine O 0
the O 0
reporting O 0
rate O 0
of O 0
hyponatremia B-Disease 0
and O 0
/ O 0
or O 0
syndrome B-Disease 0
of I-Disease 0
inappropriate I-Disease 0
secretion I-Disease 0
of I-Disease 0
anti I-Disease 0
- I-Disease 0
diuretic I-Disease 0
hormone I-Disease 0
( O 0
SIADH B-Disease 0
) O 0
among O 0
vincristine B-Chemical 0
- O 0
treated O 0
patients O 0
and O 0
to O 0
explore O 0
the O 0
possibility O 0
of O 0
at O 0
- O 0
risk O 0
population O 0
subgroups O 0
. O 0

METHOD O 0
: O 0
We O 0
searched O 0
the O 0
Eli O 0
Lilly O 0
and O 0
Company O 0
' O 0
s O 0
computerized O 0
adverse O 0
event O 0
database O 0
for O 0
all O 0
reported O 0
cases O 0
of O 0
hyponatremia B-Disease 0
and O 0
/ O 0
or O 0
SIADH B-Disease 0
as O 0
of O 0
1 O 0
November O 0
1999 O 0
that O 0
had O 0
been O 0
reported O 0
during O 0
the O 0
use O 0
of O 0
vincristine B-Chemical 0
. O 0

RESULTS O 0
: O 0
A O 0
total O 0
of O 0
76 O 0
cases O 0
of O 0
hyponatremia B-Disease 0
and O 0
/ O 0
or O 0
SIADH B-Disease 0
associated O 0
with O 0
vincristine B-Chemical 0
use O 0
were O 0
identified O 0
. O 0

The O 0
overall O 0
reporting O 0
rate O 0
was O 0
estimated O 0
to O 0
be O 0
1 O 0
. O 0
3 O 0
/ O 0
100 O 0
, O 0
000 O 0
treated O 0
patients O 0
. O 0

The O 0
average O 0
age O 0
of O 0
patients O 0
was O 0
35 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
28 O 0
. O 0
3 O 0
years O 0
, O 0
and O 0
62 O 0
% O 0
were O 0
males O 0
. O 0

Approximately O 0
75 O 0
% O 0
of O 0
the O 0
patients O 0
were O 0
receiving O 0
treatment O 0
for O 0
leukemia B-Disease 0
or O 0
lymphoma B-Disease 0
. O 0

Among O 0
the O 0
39 O 0
reports O 0
that O 0
included O 0
information O 0
on O 0
race O 0
, O 0
the O 0
racial O 0
distribution O 0
was O 0
: O 0
1 O 0
Black O 0
, O 0
3 O 0
Caucasian O 0
, O 0
and O 0
35 O 0
Asian O 0
. O 0

CONCLUSION O 0
: O 0
Our O 0
data O 0
suggest O 0
that O 0
Asian O 0
patients O 0
may O 0
be O 0
at O 0
increased O 0
risk O 0
of O 0
hyponatremia B-Disease 0
and O 0
/ O 0
or O 0
SIADH B-Disease 0
associated O 0
with O 0
vincristine B-Chemical 0
use O 0
. O 0

Although O 0
the O 0
overall O 0
reported O 0
rate O 0
of O 0
SIADH B-Disease 0
associated O 0
with O 0
vincristine B-Chemical 0
is O 0
very O 0
low O 0
, O 0
physicians O 0
caring O 0
for O 0
Asian O 0
oncology O 0
patients O 0
should O 0
be O 0
aware O 0
of O 0
this O 0
potential O 0
serious O 0
but O 0
reversible O 0
adverse O 0
event O 0
. O 0

Delayed O 0
toxicity B-Disease 0
of O 0
cyclophosphamide B-Chemical 0
on O 0
the O 0
bladder O 0
of O 0
DBA O 0
/ O 0
2 O 0
and O 0
C57BL O 0
/ O 0
6 O 0
female O 0
mouse O 0
. O 0

The O 0
present O 0
study O 0
describes O 0
the O 0
delayed O 0
development O 0
of O 0
a O 0
severe O 0
bladder O 0
pathology O 0
in O 0
a O 0
susceptible O 0
strain O 0
of O 0
mice O 0
( O 0
DBA O 0
/ O 0
2 O 0
) O 0
but O 0
not O 0
in O 0
a O 0
resistant O 0
strain O 0
( O 0
C57BL O 0
/ O 0
6 O 0
) O 0
when O 0
both O 0
were O 0
treated O 0
with O 0
a O 0
single O 0
300 O 0
mg O 0
/ O 0
kg O 0
dose O 0
of O 0
cyclophosphamide B-Chemical 0
( O 0
CY B-Chemical 0
) O 0
. O 0

Inbred O 0
DBA O 0
/ O 0
2 O 0
and O 0
C57BL O 0
/ O 0
6 O 0
female O 0
mice O 0
were O 0
injected O 0
with O 0
CY B-Chemical 0
, O 0
and O 0
the O 0
effect O 0
of O 0
the O 0
drug O 0
on O 0
the O 0
bladder O 0
was O 0
assessed O 0
during O 0
100 O 0
days O 0
by O 0
light O 0
microscopy O 0
using O 0
different O 0
staining O 0
procedures O 0
, O 0
and O 0
after O 0
30 O 0
days O 0
by O 0
conventional O 0
electron O 0
microscopy O 0
. O 0

Early O 0
CY B-Chemical 0
toxicity B-Disease 0
caused O 0
a O 0
typical O 0
haemorrhagic B-Disease 0
cystitis B-Disease 0
in O 0
both O 0
strains O 0
that O 0
was O 0
completely O 0
repaired O 0
in O 0
about O 0
7 O 0
- O 0
10 O 0
days O 0
. O 0

After O 0
30 O 0
days O 0
of O 0
CY B-Chemical 0
injection O 0
ulcerous O 0
and O 0
non O 0
- O 0
ulcerous O 0
forms O 0
of O 0
chronic O 0
cystitis B-Disease 0
appeared O 0
in O 0
86 O 0
% O 0
of O 0
DBA O 0
/ O 0
2 O 0
mice O 0
but O 0
only O 0
in O 0
4 O 0
% O 0
of O 0
C57BL O 0
/ O 0
6 O 0
mice O 0
. O 0

Delayed O 0
cystitis B-Disease 0
was O 0
characterized O 0
by O 0
infiltration O 0
and O 0
transepithelial O 0
passage O 0
into O 0
the O 0
lumen O 0
of O 0
inflammatory O 0
cells O 0
and O 0
by O 0
frequent O 0
exfoliation O 0
of O 0
the O 0
urothelium O 0
. O 0

Mast O 0
cells O 0
appeared O 0
in O 0
the O 0
connective O 0
and O 0
muscular O 0
layers O 0
of O 0
the O 0
bladder O 0
at O 0
a O 0
much O 0
higher O 0
number O 0
in O 0
DBA O 0
/ O 0
2 O 0
mice O 0
than O 0
in O 0
C57BL O 0
/ O 0
6 O 0
mice O 0
or O 0
untreated O 0
controls O 0
. O 0

Electron O 0
microscopy O 0
disclosed O 0
the O 0
absence O 0
of O 0
the O 0
typical O 0
discoidal O 0
vesicles O 0
normally O 0
present O 0
in O 0
the O 0
cytoplasm O 0
of O 0
surface O 0
cells O 0
. O 0

Instead O 0
, O 0
numerous O 0
abnormal O 0
vesicles O 0
containing O 0
one O 0
or O 0
several O 0
dark O 0
granules O 0
were O 0
observed O 0
in O 0
the O 0
cytoplasm O 0
of O 0
cells O 0
from O 0
all O 0
the O 0
epithelial O 0
layers O 0
. O 0

Delayed O 0
cystitis B-Disease 0
still O 0
persisted O 0
in O 0
DBA O 0
/ O 0
2 O 0
mice O 0
100 O 0
days O 0
after O 0
treatment O 0
. O 0

These O 0
results O 0
indicate O 0
that O 0
delayed O 0
toxicity B-Disease 0
of O 0
CY B-Chemical 0
in O 0
female O 0
DBA O 0
/ O 0
2 O 0
mice O 0
causes O 0
a O 0
bladder O 0
pathology O 0
that O 0
is O 0
not O 0
observed O 0
in O 0
C57BL O 0
/ O 0
6 O 0
mice O 0
. O 0

This O 0
pathology O 0
resembles O 0
interstitial B-Disease 0
cystitis I-Disease 0
in O 0
humans O 0
and O 0
could O 0
perhaps O 0
be O 0
used O 0
as O 0
an O 0
animal O 0
model O 0
for O 0
studies O 0
on O 0
the O 0
disease O 0
. O 0

High O 0
- O 0
dose O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
/ O 0
folinic B-Chemical 0
acid I-Chemical 0
in O 0
combination O 0
with O 0
three O 0
- O 0
weekly O 0
mitomycin B-Chemical 0
C I-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
advanced O 0
gastric B-Disease 0
cancer I-Disease 0
. O 0

A O 0
phase O 0
II O 0
study O 0
. O 0

BACKGROUND O 0
: O 0
The O 0
24 O 0
- O 0
hour O 0
continuous O 0
infusion O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
( O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
) O 0
and O 0
folinic B-Chemical 0
acid I-Chemical 0
( O 0
FA B-Chemical 0
) O 0
as O 0
part O 0
of O 0
several O 0
new O 0
multidrug O 0
chemotherapy O 0
regimens O 0
in O 0
advanced O 0
gastric B-Disease 0
cancer I-Disease 0
( O 0
AGC B-Disease 0
) O 0
has O 0
shown O 0
to O 0
be O 0
effective O 0
, O 0
with O 0
low O 0
toxicity B-Disease 0
. O 0

In O 0
a O 0
previous O 0
phase O 0
II O 0
study O 0
with O 0
3 O 0
- O 0
weekly O 0
bolus O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
, O 0
FA B-Chemical 0
and O 0
mitomycin B-Chemical 0
C I-Chemical 0
( O 0
MMC B-Chemical 0
) O 0
we O 0
found O 0
a O 0
low O 0
toxicity B-Disease 0
rate O 0
and O 0
response O 0
rates O 0
comparable O 0
to O 0
those O 0
of O 0
regimens O 0
such O 0
as O 0
ELF O 0
, O 0
FAM O 0
or O 0
FAMTX O 0
, O 0
and O 0
a O 0
promising O 0
median O 0
overall O 0
survival O 0
. O 0

In O 0
order O 0
to O 0
improve O 0
this O 0
MMC B-Chemical 0
- O 0
dependent O 0
schedule O 0
we O 0
initiated O 0
a O 0
phase O 0
II O 0
study O 0
with O 0
high O 0
- O 0
dose O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
/ O 0
FA B-Chemical 0
and O 0
3 O 0
- O 0
weekly O 0
bolus O 0
MMC B-Chemical 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
From O 0
February O 0
, O 0
1998 O 0
to O 0
September O 0
, O 0
2000 O 0
we O 0
recruited O 0
33 O 0
patients O 0
with O 0
AGC B-Disease 0
to O 0
receive O 0
weekly O 0
24 O 0
- O 0
hour O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
2 O 0
, O 0
600 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
preceded O 0
by O 0
2 O 0
- O 0
hour O 0
FA B-Chemical 0
500 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
for O 0
6 O 0
weeks O 0
, O 0
followed O 0
by O 0
a O 0
2 O 0
- O 0
week O 0
rest O 0
period O 0
. O 0

Bolus O 0
MMC B-Chemical 0
10 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
was O 0
added O 0
in O 0
3 O 0
- O 0
weekly O 0
intervals O 0
. O 0

Treatment O 0
given O 0
on O 0
an O 0
outpatient O 0
basis O 0
, O 0
using O 0
portable O 0
pump O 0
systems O 0
, O 0
was O 0
repeated O 0
on O 0
day O 0
57 O 0
. O 0

Patients O 0
' O 0
characteristics O 0
were O 0
: O 0
male O 0
/ O 0
female O 0
ratio O 0
20 O 0
/ O 0
13 O 0
; O 0
median O 0
age O 0
57 O 0
( O 0
27 O 0
- O 0
75 O 0
) O 0
years O 0
; O 0
median O 0
WHO O 0
status O 0
1 O 0
( O 0
0 O 0
- O 0
2 O 0
) O 0
. O 0

18 O 0
patients O 0
had O 0
a O 0
primary O 0
AGC B-Disease 0
, O 0
and O 0
15 O 0
showed O 0
a O 0
relapsed O 0
AGC B-Disease 0
. O 0

Median O 0
follow O 0
- O 0
up O 0
was O 0
11 O 0
. O 0
8 O 0
months O 0
( O 0
range O 0
of O 0
those O 0
surviving O 0
: O 0
2 O 0
. O 0
7 O 0
- O 0
11 O 0
. O 0
8 O 0
months O 0
) O 0
. O 0

RESULTS O 0
: O 0
32 O 0
patients O 0
were O 0
evaluable O 0
for O 0
response O 0
- O 0
complete O 0
remission O 0
9 O 0
. O 0
1 O 0
% O 0
( O 0
n O 0
= O 0
3 O 0
) O 0
, O 0
partial O 0
remission O 0
45 O 0
. O 0
5 O 0
% O 0
( O 0
n O 0
= O 0
15 O 0
) O 0
, O 0
no O 0
change O 0
27 O 0
. O 0
3 O 0
% O 0
( O 0
n O 0
= O 0
9 O 0
) O 0
, O 0
progressive O 0
disease O 0
15 O 0
. O 0
1 O 0
% O 0
( O 0
n O 0
= O 0
5 O 0
) O 0
. O 0

Median O 0
overall O 0
survival O 0
time O 0
was O 0
10 O 0
. O 0
2 O 0
months O 0
[ O 0
95 O 0
% O 0
confidence O 0
interval O 0
( O 0
CI O 0
) O 0
: O 0
8 O 0
. O 0
7 O 0
- O 0
11 O 0
. O 0
6 O 0
] O 0
, O 0
and O 0
median O 0
progression O 0
- O 0
free O 0
survival O 0
time O 0
was O 0
7 O 0
. O 0
6 O 0
months O 0
( O 0
95 O 0
% O 0
CI O 0
: O 0
4 O 0
. O 0
4 O 0
- O 0
10 O 0
. O 0
9 O 0
) O 0
. O 0

The O 0
worst O 0
toxicities B-Disease 0
( O 0
% O 0
) O 0
observed O 0
were O 0
( O 0
CTC O 0
- O 0
NCI O 0
1 O 0
/ O 0
2 O 0
/ O 0
3 O 0
) O 0
: O 0
leukopenia B-Disease 0
45 O 0
. O 0
5 O 0
/ O 0
18 O 0
. O 0
2 O 0
/ O 0
6 O 0
. O 0
1 O 0
, O 0
thrombocytopenia B-Disease 0
33 O 0
. O 0
3 O 0
/ O 0
9 O 0
. O 0
1 O 0
/ O 0
6 O 0
. O 0
1 O 0
, O 0
vomitus B-Disease 0
24 O 0
. O 0
2 O 0
/ O 0
9 O 0
. O 0
1 O 0
/ O 0
0 O 0
, O 0
diarrhea B-Disease 0
36 O 0
. O 0
4 O 0
/ O 0
6 O 0
. O 0
1 O 0
/ O 0
3 O 0
. O 0
0 O 0
, O 0
stomatitis B-Disease 0
18 O 0
. O 0
2 O 0
/ O 0
9 O 0
. O 0
1 O 0
/ O 0
0 O 0
, O 0
hand B-Disease 0
- I-Disease 0
foot I-Disease 0
syndrome I-Disease 0
12 O 0
. O 0
1 O 0
/ O 0
0 O 0
/ O 0
0 O 0
. O 0

Two O 0
patients O 0
developed O 0
hemolytic B-Disease 0
- I-Disease 0
uremic I-Disease 0
syndrome I-Disease 0
( O 0
HUS B-Disease 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
High O 0
- O 0
dose O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
/ O 0
FA B-Chemical 0
/ O 0
MMC B-Chemical 0
is O 0
an O 0
effective O 0
and O 0
well O 0
- O 0
tolerated O 0
outpatient O 0
regimen O 0
for O 0
AGC B-Disease 0
( O 0
objective O 0
response O 0
rate O 0
54 O 0
. O 0
6 O 0
% O 0
) O 0
. O 0

It O 0
may O 0
serve O 0
as O 0
an O 0
alternative O 0
to O 0
cisplatin B-Chemical 0
- O 0
containing O 0
regimens O 0
; O 0
however O 0
, O 0
it O 0
has O 0
to O 0
be O 0
considered O 0
that O 0
possibly O 0
HUS B-Disease 0
may O 0
occur O 0
. O 0

Persistent O 0
sterile O 0
leukocyturia B-Disease 0
is O 0
associated O 0
with O 0
impaired B-Disease 0
renal I-Disease 0
function I-Disease 0
in O 0
human B-Disease 0
immunodeficiency I-Disease 0
virus I-Disease 0
type I-Disease 0
1 I-Disease 0
- I-Disease 0
infected I-Disease 0
children O 0
treated O 0
with O 0
indinavir B-Chemical 0
. O 0

BACKGROUND O 0
: O 0
Prolonged O 0
administration O 0
of O 0
indinavir B-Chemical 0
is O 0
associated O 0
with O 0
the O 0
occurrence O 0
of O 0
a O 0
variety O 0
of O 0
renal O 0
complications O 0
in O 0
adults O 0
. O 0

These O 0
well O 0
- O 0
documented O 0
side O 0
effects O 0
have O 0
restricted O 0
the O 0
use O 0
of O 0
this O 0
potent O 0
protease O 0
inhibitor O 0
in O 0
children O 0
. O 0

DESIGN O 0
: O 0
A O 0
prospective O 0
study O 0
to O 0
monitor O 0
indinavir B-Chemical 0
- O 0
related O 0
nephrotoxicity B-Disease 0
in O 0
a O 0
cohort O 0
of O 0
30 O 0
human B-Disease 0
immunodeficiency I-Disease 0
virus I-Disease 0
type I-Disease 0
1 I-Disease 0
- I-Disease 0
infected I-Disease 0
children O 0
treated O 0
with O 0
indinavir B-Chemical 0
. O 0

METHODS O 0
: O 0
Urinary O 0
pH O 0
, O 0
albumin O 0
, O 0
creatinine B-Chemical 0
, O 0
the O 0
presence O 0
of O 0
erythrocytes O 0
, O 0
leukocytes O 0
, O 0
bacteria O 0
and O 0
crystals O 0
, O 0
and O 0
culture O 0
were O 0
analyzed O 0
every O 0
3 O 0
months O 0
for O 0
96 O 0
weeks O 0
. O 0

Serum O 0
creatinine B-Chemical 0
levels O 0
were O 0
routinely O 0
determined O 0
at O 0
the O 0
same O 0
time O 0
points O 0
. O 0

Steady O 0
- O 0
state O 0
pharmacokinetics O 0
of O 0
indinavir B-Chemical 0
were O 0
done O 0
at O 0
week O 0
4 O 0
after O 0
the O 0
initiation O 0
of O 0
indinavir B-Chemical 0
. O 0

RESULTS O 0
: O 0
The O 0
cumulative O 0
incidence O 0
of O 0
persistent O 0
sterile O 0
leukocyturia B-Disease 0
( O 0
> O 0
or O 0
= O 0
75 O 0
cells O 0
/ O 0
micro O 0
L O 0
in O 0
at O 0
least O 0
2 O 0
consecutive O 0
visits O 0
) O 0
after O 0
96 O 0
weeks O 0
was O 0
53 O 0
% O 0
. O 0

Persistent O 0
sterile O 0
leukocyturia B-Disease 0
was O 0
frequently O 0
associated O 0
with O 0
a O 0
mild O 0
increase O 0
in O 0
the O 0
urine O 0
albumin O 0
/ O 0
creatinine B-Chemical 0
ratio O 0
and O 0
by O 0
microscopic O 0
hematuria B-Disease 0
. O 0

The O 0
cumulative O 0
incidence O 0
of O 0
serum O 0
creatinine B-Chemical 0
levels O 0
> O 0
50 O 0
% O 0
above O 0
normal O 0
was O 0
33 O 0
% O 0
after O 0
96 O 0
weeks O 0
. O 0

Children O 0
with O 0
persistent O 0
sterile O 0
leukocyturia B-Disease 0
more O 0
frequently O 0
had O 0
serum O 0
creatinine B-Chemical 0
levels O 0
of O 0
50 O 0
% O 0
above O 0
normal O 0
than O 0
those O 0
children O 0
without O 0
persistent O 0
sterile O 0
leukocyturia B-Disease 0
. O 0

In O 0
children O 0
younger O 0
than O 0
5 O 0
. O 0
6 O 0
years O 0
, O 0
persistent O 0
sterile O 0
leukocyturia B-Disease 0
was O 0
significantly O 0
more O 0
frequent O 0
than O 0
in O 0
older O 0
children O 0
. O 0

A O 0
higher O 0
cumulative O 0
incidence O 0
of O 0
persistent O 0
leukocyturia B-Disease 0
was O 0
found O 0
in O 0
children O 0
with O 0
an O 0
area O 0
under O 0
the O 0
curve O 0
> O 0
19 O 0
mg O 0
/ O 0
L O 0
x O 0
h O 0
or O 0
a O 0
peak O 0
serum O 0
level O 0
of O 0
indinavir B-Chemical 0
> O 0
12 O 0
mg O 0
/ O 0
L O 0
. O 0

In O 0
4 O 0
children O 0
, O 0
indinavir B-Chemical 0
was O 0
discontinued O 0
because O 0
of O 0
nephrotoxicity B-Disease 0
. O 0

Subsequently O 0
, O 0
the O 0
serum O 0
creatinine B-Chemical 0
levels O 0
decreased O 0
, O 0
the O 0
urine O 0
albumin O 0
/ O 0
creatinine B-Chemical 0
ratios O 0
returned O 0
to O 0
zero O 0
, O 0
and O 0
the O 0
leukocyturia B-Disease 0
disappeared O 0
within O 0
3 O 0
months O 0
. O 0

CONCLUSIONS O 0
: O 0
Children O 0
treated O 0
with O 0
indinavir B-Chemical 0
have O 0
a O 0
high O 0
cumulative O 0
incidence O 0
of O 0
persistent O 0
sterile O 0
leukocyturia B-Disease 0
. O 0

Children O 0
with O 0
persistent O 0
sterile O 0
leukocyturia B-Disease 0
more O 0
frequently O 0
had O 0
an O 0
increase O 0
in O 0
serum O 0
creatinine B-Chemical 0
levels O 0
of O 0
> O 0
50 O 0
% O 0
above O 0
normal O 0
. O 0

Younger O 0
children O 0
have O 0
an O 0
additional O 0
risk O 0
for O 0
renal O 0
complications O 0
. O 0

The O 0
impairment B-Disease 0
of I-Disease 0
the I-Disease 0
renal I-Disease 0
function I-Disease 0
in O 0
these O 0
children O 0
occurred O 0
in O 0
the O 0
absence O 0
of O 0
clinical O 0
symptoms O 0
of O 0
nephrolithiasis B-Disease 0
. O 0

Indinavir B-Chemical 0
- O 0
associated O 0
nephrotoxicity B-Disease 0
must O 0
be O 0
monitored O 0
closely O 0
, O 0
especially O 0
in O 0
children O 0
with O 0
risk O 0
factors O 0
such O 0
as O 0
persistent O 0
sterile O 0
leukocyturia B-Disease 0
, O 0
age O 0
< O 0
5 O 0
. O 0
6 O 0
years O 0
, O 0
an O 0
area O 0
under O 0
the O 0
curve O 0
of O 0
indinavir B-Chemical 0
> O 0
19 O 0
mg O 0
/ O 0
L O 0
x O 0
h O 0
, O 0
and O 0
a O 0
C O 0
( O 0
max O 0
) O 0
> O 0
12 O 0
mg O 0
/ O 0
L O 0
. O 0

Utility O 0
of O 0
troponin O 0
I O 0
in O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
. O 0

Baseline O 0
electrocardiogram O 0
abnormalities O 0
and O 0
market O 0
elevations O 0
not O 0
associated O 0
with O 0
myocardial B-Disease 0
necrosis I-Disease 0
make O 0
accurate O 0
diagnosis O 0
of O 0
myocardial B-Disease 0
infarction I-Disease 0
( O 0
MI B-Disease 0
) O 0
difficult O 0
in O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
. O 0

Troponin O 0
sampling O 0
may O 0
offer O 0
greater O 0
diagnostic O 0
utility O 0
in O 0
these O 0
patients O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
assess O 0
outcomes O 0
based O 0
on O 0
troponin O 0
positivity O 0
in O 0
patients O 0
with O 0
cocaine B-Chemical 0
chest B-Disease 0
pain I-Disease 0
admitted O 0
for O 0
exclusion O 0
of O 0
MI B-Disease 0
. O 0

METHODS O 0
: O 0
Outcomes O 0
were O 0
examined O 0
in O 0
patients O 0
admitted O 0
for O 0
possible O 0
MI B-Disease 0
after O 0
cocaine B-Chemical 0
use O 0
. O 0

All O 0
patients O 0
underwent O 0
a O 0
rapid O 0
rule O 0
- O 0
in O 0
protocol O 0
that O 0
included O 0
serial O 0
sampling O 0
of O 0
creatine B-Chemical 0
kinase O 0
( O 0
CK O 0
) O 0
, O 0
CK O 0
- O 0
MB O 0
, O 0
and O 0
cardiac O 0
troponin O 0
I O 0
( O 0
cTnI O 0
) O 0
over O 0
eight O 0
hours O 0
. O 0

Outcomes O 0
included O 0
CK O 0
- O 0
MB O 0
MI B-Disease 0
( O 0
CK O 0
- O 0
MB O 0
> O 0
or O 0
= O 0
8 O 0
ng O 0
/ O 0
mL O 0
with O 0
a O 0
relative O 0
index O 0
[ O 0
( O 0
CK O 0
- O 0
MB O 0
x O 0
100 O 0
) O 0
/ O 0
total O 0
CK O 0
] O 0
> O 0
or O 0
= O 0
4 O 0
, O 0
cardiac B-Disease 0
death I-Disease 0
, O 0
and O 0
significant O 0
coronary B-Disease 0
disease I-Disease 0
( O 0
> O 0
or O 0
= O 0
50 O 0
% O 0
) O 0
. O 0

RESULTS O 0
: O 0
Of O 0
the O 0
246 O 0
admitted O 0
patients O 0
, O 0
34 O 0
( O 0
14 O 0
% O 0
) O 0
met O 0
CK O 0
- O 0
MB O 0
criteria O 0
for O 0
MI B-Disease 0
and O 0
38 O 0
( O 0
16 O 0
% O 0
) O 0
had O 0
cTnI O 0
elevations O 0
. O 0

Angiography O 0
was O 0
performed O 0
in O 0
29 O 0
of O 0
38 O 0
patients O 0
who O 0
were O 0
cTnI O 0
- O 0
positive O 0
, O 0
with O 0
significant O 0
disease O 0
present O 0
in O 0
25 O 0
( O 0
86 O 0
% O 0
) O 0
. O 0

Three O 0
of O 0
the O 0
four O 0
patients O 0
without O 0
significant O 0
disease O 0
who O 0
had O 0
cTnI O 0
elevations O 0
met O 0
CK O 0
- O 0
MB O 0
criteria O 0
for O 0
MI B-Disease 0
, O 0
and O 0
the O 0
other O 0
had O 0
a O 0
peak O 0
CK O 0
- O 0
MB O 0
level O 0
of O 0
13 O 0
ng O 0
/ O 0
mL O 0
. O 0

Sensitivities O 0
, O 0
specificities O 0
, O 0
and O 0
positive O 0
and O 0
negative O 0
likelihood O 0
ratios O 0
for O 0
predicting O 0
cardiac B-Disease 0
death I-Disease 0
or O 0
significant O 0
disease O 0
were O 0
high O 0
for O 0
both O 0
CK O 0
- O 0
MB O 0
MI B-Disease 0
and O 0
cTnI O 0
and O 0
were O 0
not O 0
significantly O 0
different O 0
. O 0

CONCLUSIONS O 0
: O 0
Most O 0
patients O 0
with O 0
cTnI O 0
elevations O 0
meet O 0
CK O 0
- O 0
MB O 0
criteria O 0
for O 0
MI B-Disease 0
, O 0
as O 0
well O 0
as O 0
have O 0
a O 0
high O 0
incidence O 0
of O 0
underlying O 0
significant O 0
disease O 0
. O 0

Troponin O 0
appears O 0
to O 0
have O 0
an O 0
equivalent O 0
diagnostic O 0
accuracy O 0
compared O 0
with O 0
CK O 0
- O 0
MB O 0
for O 0
diagnosing O 0
necrosis B-Disease 0
in O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
and O 0
suspected O 0
MI B-Disease 0
. O 0

Acute O 0
interstitial B-Disease 0
nephritis I-Disease 0
due O 0
to O 0
nicergoline B-Chemical 0
( O 0
Sermion B-Chemical 0
) O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
acute O 0
interstitial B-Disease 0
nephritis I-Disease 0
( O 0
AIN B-Disease 0
) O 0
due O 0
to O 0
nicergoline B-Chemical 0
( O 0
Sermion B-Chemical 0
) O 0
. O 0

A O 0
50 O 0
- O 0
year O 0
- O 0
old O 0
patient O 0
admitted O 0
to O 0
our O 0
hospital O 0
for O 0
fever B-Disease 0
and O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
. O 0

Before O 0
admission O 0
, O 0
he O 0
had O 0
been O 0
taking O 0
nicergoline B-Chemical 0
and O 0
bendazac B-Chemical 0
lysine I-Chemical 0
due O 0
to O 0
retinal B-Disease 0
vein I-Disease 0
occlusion I-Disease 0
at O 0
ophthalmologic O 0
department O 0
. O 0

Thereafter O 0
, O 0
he O 0
experienced O 0
intermittent O 0
fever B-Disease 0
and O 0
skin B-Disease 0
rash I-Disease 0
. O 0

On O 0
admission O 0
, O 0
clinical O 0
symptoms O 0
( O 0
i O 0
. O 0
e O 0
. O 0
arthralgia B-Disease 0
and O 0
fever B-Disease 0
) O 0
and O 0
laboratory O 0
findings O 0
( O 0
i O 0
. O 0
e O 0
. O 0
eosinophilia B-Disease 0
and O 0
renal B-Disease 0
failure I-Disease 0
) O 0
suggested O 0
AIN B-Disease 0
, O 0
and O 0
which O 0
was O 0
confirmed O 0
by O 0
pathologic O 0
findings O 0
on O 0
renal O 0
biopsy O 0
. O 0

A O 0
lymphocyte O 0
transformation O 0
test O 0
demonstrated O 0
a O 0
positive O 0
result O 0
against O 0
nicergoline B-Chemical 0
. O 0

Treatment O 0
was O 0
consisted O 0
of O 0
withdrawal O 0
of O 0
nicergoline B-Chemical 0
and O 0
intravenous O 0
methylprednisolone B-Chemical 0
, O 0
and O 0
his O 0
renal O 0
function O 0
was O 0
completely O 0
recovered O 0
. O 0

To O 0
our O 0
knowledge O 0
, O 0
this O 0
is O 0
the O 0
first O 0
report O 0
of O 0
nicergoline B-Chemical 0
- O 0
associated O 0
AIN B-Disease 0
. O 0

Neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
complicated O 0
by O 0
massive O 0
intestinal O 0
bleeding B-Disease 0
in O 0
a O 0
patient O 0
with O 0
chronic B-Disease 0
renal I-Disease 0
failure I-Disease 0
. O 0

A O 0
patient O 0
with O 0
chronic B-Disease 0
renal I-Disease 0
failure I-Disease 0
( O 0
CRF B-Disease 0
) O 0
developed O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
( O 0
NMS B-Disease 0
) O 0
after O 0
administration O 0
of O 0
risperidone B-Chemical 0
and O 0
levomepromazine B-Chemical 0
. O 0

In O 0
addition O 0
to O 0
the O 0
typical O 0
symptoms O 0
of O 0
NMS B-Disease 0
, O 0
massive O 0
intestinal O 0
bleeding B-Disease 0
was O 0
observed O 0
during O 0
the O 0
episode O 0
. O 0

This O 0
report O 0
suggests O 0
that O 0
NMS B-Disease 0
in O 0
a O 0
patient O 0
with O 0
CRF B-Disease 0
may O 0
be O 0
complicated O 0
by O 0
intestinal O 0
bleeding B-Disease 0
and O 0
needs O 0
special O 0
caution O 0
for O 0
this O 0
complication O 0
. O 0

Blood O 0
brain O 0
barrier O 0
in O 0
right O 0
- O 0
and O 0
left O 0
- O 0
pawed O 0
female O 0
rats O 0
assessed O 0
by O 0
a O 0
new O 0
staining O 0
method O 0
. O 0

The O 0
asymmetrical O 0
breakdown O 0
of O 0
the O 0
blood O 0
- O 0
brain O 0
barrier O 0
( O 0
BBB O 0
) O 0
was O 0
studied O 0
in O 0
female O 0
rats O 0
. O 0

Paw O 0
preference O 0
was O 0
assessed O 0
by O 0
a O 0
food O 0
reaching O 0
test O 0
. O 0

Adrenaline B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
was O 0
used O 0
to O 0
destroy O 0
the O 0
BBB O 0
, O 0
which O 0
was O 0
evaluated O 0
using O 0
triphenyltetrazolium B-Chemical 0
( O 0
TTC B-Chemical 0
) O 0
staining O 0
of O 0
the O 0
brain O 0
slices O 0
just O 0
after O 0
giving O 0
adrenaline B-Chemical 0
for O 0
30 O 0
s O 0
. O 0

In O 0
normal O 0
rats O 0
, O 0
the O 0
whole O 0
brain O 0
sections O 0
exhibited O 0
complete O 0
staining O 0
with O 0
TTC B-Chemical 0
. O 0

After O 0
adrenaline B-Chemical 0
infusion O 0
for O 0
30 O 0
s O 0
, O 0
there O 0
were O 0
large O 0
unstained O 0
areas O 0
in O 0
the O 0
left O 0
brain O 0
in O 0
right O 0
- O 0
pawed O 0
animals O 0
, O 0
and O 0
vice O 0
versa O 0
in O 0
left O 0
- O 0
pawed O 0
animals O 0
. O 0

Similar O 0
results O 0
were O 0
obtained O 0
in O 0
seizure B-Disease 0
- O 0
induced O 0
breakdown O 0
of O 0
BBB O 0
. O 0

These O 0
results O 0
were O 0
explained O 0
by O 0
an O 0
asymmetric O 0
cerebral O 0
blood O 0
flow O 0
depending O 0
upon O 0
the O 0
paw O 0
preference O 0
in O 0
rats O 0
. O 0

It O 0
was O 0
suggested O 0
that O 0
this O 0
new O 0
method O 0
and O 0
the O 0
results O 0
are O 0
consistent O 0
with O 0
contralateral O 0
motor O 0
control O 0
that O 0
may O 0
be O 0
important O 0
in O 0
determining O 0
the O 0
dominant O 0
cerebral O 0
hemisphere O 0
in O 0
animals O 0
. O 0

Carvedilol B-Chemical 0
protects O 0
against O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
mitochondrial O 0
cardiomyopathy B-Disease 0
. O 0

Several O 0
cytopathic O 0
mechanisms O 0
have O 0
been O 0
suggested O 0
to O 0
mediate O 0
the O 0
dose O 0
- O 0
limiting O 0
cumulative O 0
and O 0
irreversible O 0
cardiomyopathy B-Disease 0
caused O 0
by O 0
doxorubicin B-Chemical 0
. O 0

Recent O 0
evidence O 0
indicates O 0
that O 0
oxidative O 0
stress O 0
and O 0
mitochondrial B-Disease 0
dysfunction I-Disease 0
are O 0
key O 0
factors O 0
in O 0
the O 0
pathogenic O 0
process O 0
. O 0

The O 0
objective O 0
of O 0
this O 0
investigation O 0
was O 0
to O 0
test O 0
the O 0
hypothesis O 0
that O 0
carvedilol B-Chemical 0
, O 0
a O 0
nonselective O 0
beta O 0
- O 0
adrenergic O 0
receptor O 0
antagonist O 0
with O 0
potent O 0
antioxidant O 0
properties O 0
, O 0
protects O 0
against O 0
the O 0
cardiac O 0
and O 0
hepatic O 0
mitochondrial O 0
bioenergetic O 0
dysfunction O 0
associated O 0
with O 0
subchronic O 0
doxorubicin B-Chemical 0
toxicity B-Disease 0
. O 0

Heart O 0
and O 0
liver O 0
mitochondria O 0
were O 0
isolated O 0
from O 0
rats O 0
treated O 0
for O 0
7 O 0
weeks O 0
with O 0
doxorubicin B-Chemical 0
( O 0
2 O 0
mg O 0
/ O 0
kg O 0
sc O 0
/ O 0
week O 0
) O 0
, O 0
carvedilol B-Chemical 0
( O 0
1 O 0
mg O 0
/ O 0
kg O 0
ip O 0
/ O 0
week O 0
) O 0
, O 0
or O 0
the O 0
combination O 0
of O 0
the O 0
two O 0
drugs O 0
. O 0

Heart O 0
mitochondria O 0
isolated O 0
from O 0
doxorubicin B-Chemical 0
- O 0
treated O 0
rats O 0
exhibited O 0
depressed O 0
rates O 0
for O 0
state O 0
3 O 0
respiration O 0
( O 0
336 O 0
+ O 0
/ O 0
- O 0
26 O 0
versus O 0
425 O 0
+ O 0
/ O 0
- O 0
53 O 0
natom O 0
O O 0
/ O 0
min O 0
/ O 0
mg O 0
protein O 0
) O 0
and O 0
a O 0
lower O 0
respiratory O 0
control O 0
ratio O 0
( O 0
RCR O 0
) O 0
( O 0
4 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
6 O 0
versus O 0
5 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
4 O 0
) O 0
compared O 0
with O 0
cardiac O 0
mitochondria O 0
isolated O 0
from O 0
saline O 0
- O 0
treated O 0
rats O 0
. O 0

Mitochondrial O 0
calcium B-Chemical 0
- O 0
loading O 0
capacity O 0
and O 0
the O 0
activity O 0
of O 0
NADH O 0
- O 0
dehydrogenase O 0
were O 0
also O 0
suppressed O 0
in O 0
cardiac O 0
mitochondria O 0
from O 0
doxorubicin B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

Doxorubicin B-Chemical 0
treatment O 0
also O 0
caused O 0
a O 0
decrease O 0
in O 0
RCR O 0
for O 0
liver O 0
mitochondria O 0
( O 0
3 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
9 O 0
versus O 0
5 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
7 O 0
for O 0
control O 0
rats O 0
) O 0
and O 0
inhibition O 0
of O 0
hepatic O 0
cytochrome O 0
oxidase O 0
activity O 0
. O 0

Coadministration O 0
of O 0
carvedilol B-Chemical 0
decreased O 0
the O 0
extent O 0
of O 0
cellular O 0
vacuolization O 0
in O 0
cardiac O 0
myocytes O 0
and O 0
prevented O 0
the O 0
inhibitory O 0
effect O 0
of O 0
doxorubicin B-Chemical 0
on O 0
mitochondrial O 0
respiration O 0
in O 0
both O 0
heart O 0
and O 0
liver O 0
. O 0

Carvedilol B-Chemical 0
also O 0
prevented O 0
the O 0
decrease O 0
in O 0
mitochondrial O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
loading O 0
capacity O 0
and O 0
the O 0
inhibition O 0
of O 0
the O 0
respiratory O 0
complexes O 0
of O 0
heart O 0
mitochondria O 0
caused O 0
by O 0
doxorubicin B-Chemical 0
. O 0

Carvedilol B-Chemical 0
by O 0
itself O 0
did O 0
not O 0
affect O 0
any O 0
of O 0
the O 0
parameters O 0
measured O 0
for O 0
heart O 0
or O 0
liver O 0
mitochondria O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
this O 0
protection O 0
by O 0
carvedilol B-Chemical 0
against O 0
both O 0
the O 0
structural O 0
and O 0
functional O 0
cardiac O 0
tissue O 0
damage O 0
may O 0
afford O 0
significant O 0
clinical O 0
advantage O 0
in O 0
minimizing O 0
the O 0
dose O 0
- O 0
limiting O 0
mitochondrial B-Disease 0
dysfunction I-Disease 0
and O 0
cardiomyopathy B-Disease 0
that O 0
accompanies O 0
long O 0
- O 0
term O 0
doxorubicin B-Chemical 0
therapy O 0
in O 0
cancer B-Disease 0
patients O 0
. O 0

Cocaine B-Chemical 0
- O 0
induced O 0
hyperactivity B-Disease 0
is O 0
more O 0
influenced O 0
by O 0
adenosine B-Chemical 0
receptor O 0
agonists O 0
than O 0
amphetamine B-Chemical 0
- O 0
induced O 0
hyperactivity B-Disease 0
. O 0

The O 0
influence O 0
of O 0
adenosine B-Chemical 0
receptor O 0
agonists O 0
and O 0
antagonists O 0
on O 0
cocaine B-Chemical 0
- O 0
and O 0
amphetamine B-Chemical 0
- O 0
induced O 0
hyperactivity B-Disease 0
was O 0
examined O 0
in O 0
mice O 0
. O 0

All O 0
adenosine B-Chemical 0
receptor O 0
agonists O 0
significantly O 0
decreased B-Disease 0
the I-Disease 0
locomotor I-Disease 0
activity I-Disease 0
in O 0
mice O 0
, O 0
and O 0
the O 0
effects O 0
were O 0
dose O 0
- O 0
dependent O 0
. O 0

It O 0
seems O 0
that O 0
adenosine B-Chemical 0
A1 O 0
and O 0
A2 O 0
receptors O 0
might O 0
be O 0
involved O 0
in O 0
this O 0
reaction O 0
. O 0

Moreover O 0
, O 0
all O 0
adenosine B-Chemical 0
receptor O 0
agonists O 0
: O 0
2 B-Chemical 0
- I-Chemical 0
p I-Chemical 0
- I-Chemical 0
( I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
carboxyethyl I-Chemical 0
) I-Chemical 0
phenethylamino I-Chemical 0
- I-Chemical 0
5 I-Chemical 0
' I-Chemical 0
- I-Chemical 0
N I-Chemical 0
- I-Chemical 0
ethylcarboxamidoadenosine I-Chemical 0
( O 0
CGS B-Chemical 0
21680 I-Chemical 0
) O 0
, O 0
A2A O 0
receptor O 0
agonist O 0
, O 0
N6 B-Chemical 0
- I-Chemical 0
cyclopentyladenosine I-Chemical 0
( O 0
CPA B-Chemical 0
) O 0
, O 0
A1 O 0
receptor O 0
agonist O 0
, O 0
and O 0
5 B-Chemical 0
' I-Chemical 0
- I-Chemical 0
N I-Chemical 0
- I-Chemical 0
ethylcarboxamidoadenosine I-Chemical 0
( O 0
NECA B-Chemical 0
) O 0
, O 0
A2 O 0
/ O 0
A1 O 0
receptor O 0
agonist O 0
significantly O 0
and O 0
dose O 0
- O 0
dependently O 0
decreased O 0
cocaine B-Chemical 0
- O 0
induced O 0
locomotor O 0
activity O 0
. O 0

CPA B-Chemical 0
reduced O 0
cocaine B-Chemical 0
action O 0
at O 0
the O 0
doses O 0
which O 0
, O 0
given O 0
alone O 0
, O 0
did O 0
not O 0
influence O 0
motility O 0
, O 0
while O 0
CGS B-Chemical 0
21680 I-Chemical 0
and O 0
NECA B-Chemical 0
decreased O 0
the O 0
action O 0
of O 0
cocaine B-Chemical 0
at O 0
the O 0
doses O 0
which O 0
, O 0
given O 0
alone O 0
, O 0
decreased O 0
locomotor O 0
activity O 0
in O 0
animals O 0
. O 0

These O 0
results O 0
suggest O 0
the O 0
involvement O 0
of O 0
both O 0
adenosine B-Chemical 0
receptors O 0
in O 0
the O 0
action O 0
of O 0
cocaine B-Chemical 0
although O 0
agonists O 0
of O 0
A1 O 0
receptors O 0
seem O 0
to O 0
have O 0
stronger O 0
influence O 0
on O 0
it O 0
. O 0

The O 0
selective O 0
blockade O 0
of O 0
A2 O 0
adenosine B-Chemical 0
receptor O 0
by O 0
DMPX B-Chemical 0
( O 0
3 B-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
dimethyl I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
propargylxanthine I-Chemical 0
) O 0
significantly O 0
enhanced O 0
cocaine B-Chemical 0
- O 0
induced O 0
locomotor O 0
activity O 0
of O 0
animals O 0
. O 0

Caffeine B-Chemical 0
had O 0
similar O 0
action O 0
but O 0
the O 0
effect O 0
was O 0
not O 0
significant O 0
. O 0

CPT B-Chemical 0
( O 0
8 B-Chemical 0
- I-Chemical 0
cyclopentyltheophylline I-Chemical 0
) O 0
- O 0
- O 0
A1 O 0
receptor O 0
antagonist O 0
, O 0
did O 0
not O 0
show O 0
any O 0
influence O 0
in O 0
this O 0
test O 0
. O 0

Similarly O 0
, O 0
all O 0
adenosine B-Chemical 0
receptor O 0
agonists O 0
decreased O 0
amphetamine B-Chemical 0
- O 0
induced O 0
hyperactivity B-Disease 0
, O 0
but O 0
at O 0
the O 0
higher O 0
doses O 0
than O 0
those O 0
which O 0
were O 0
active O 0
in O 0
cocaine B-Chemical 0
- O 0
induced O 0
hyperactivity B-Disease 0
. O 0

The O 0
selective O 0
blockade O 0
of O 0
A2 O 0
adenosine B-Chemical 0
receptors O 0
( O 0
DMPX B-Chemical 0
) O 0
and O 0
non O 0
- O 0
selective O 0
blockade O 0
of O 0
adenosine B-Chemical 0
receptors O 0
( O 0
caffeine B-Chemical 0
) O 0
significantly O 0
increased O 0
the O 0
action O 0
of O 0
amphetamine B-Chemical 0
in O 0
the O 0
locomotor O 0
activity O 0
test O 0
. O 0

Our O 0
results O 0
have O 0
shown O 0
that O 0
all O 0
adenosine B-Chemical 0
receptor O 0
agonists O 0
( O 0
A1 O 0
and O 0
A2 O 0
) O 0
reduce O 0
cocaine B-Chemical 0
- O 0
and O 0
amphetamine B-Chemical 0
- O 0
induced O 0
locomotor O 0
activity O 0
and O 0
indicate O 0
that O 0
cocaine B-Chemical 0
- O 0
induced O 0
hyperactivity B-Disease 0
is O 0
more O 0
influenced O 0
by O 0
adenosine B-Chemical 0
receptor O 0
agonists O 0
( O 0
particularly O 0
A1 O 0
receptors O 0
) O 0
than O 0
amphetamine B-Chemical 0
- O 0
induced O 0
hyperactivity B-Disease 0
. O 0

Amiodarone B-Chemical 0
and O 0
the O 0
risk O 0
of O 0
bradyarrhythmia B-Disease 0
requiring O 0
permanent O 0
pacemaker O 0
in O 0
elderly O 0
patients O 0
with O 0
atrial B-Disease 0
fibrillation I-Disease 0
and O 0
prior O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

OBJECTIVES O 0
: O 0
The O 0
aim O 0
of O 0
this O 0
study O 0
was O 0
to O 0
determine O 0
whether O 0
the O 0
use O 0
of O 0
amiodarone B-Chemical 0
in O 0
patients O 0
with O 0
atrial B-Disease 0
fibrillation I-Disease 0
( O 0
AF B-Disease 0
) O 0
increases O 0
the O 0
risk O 0
of O 0
bradyarrhythmia B-Disease 0
requiring O 0
a O 0
permanent O 0
pacemaker O 0
. O 0

BACKGROUND O 0
: O 0
Reports O 0
of O 0
severe O 0
bradyarrhythmia B-Disease 0
during O 0
amiodarone B-Chemical 0
therapy O 0
are O 0
infrequent O 0
and O 0
limited O 0
to O 0
studies O 0
assessing O 0
the O 0
therapy O 0
' O 0
s O 0
use O 0
in O 0
the O 0
management O 0
of O 0
patients O 0
with O 0
ventricular B-Disease 0
arrhythmias I-Disease 0
. O 0

METHODS O 0
: O 0
A O 0
study O 0
cohort O 0
of O 0
8 O 0
, O 0
770 O 0
patients O 0
age O 0
> O 0
or O 0
= O 0
65 O 0
years O 0
with O 0
a O 0
new O 0
diagnosis O 0
of O 0
AF B-Disease 0
was O 0
identified O 0
from O 0
a O 0
provincewide O 0
database O 0
of O 0
Quebec O 0
residents O 0
with O 0
a O 0
myocardial B-Disease 0
infarction I-Disease 0
( O 0
MI B-Disease 0
) O 0
between O 0
1991 O 0
and O 0
1999 O 0
. O 0

Using O 0
a O 0
nested O 0
case O 0
- O 0
control O 0
design O 0
, O 0
477 O 0
cases O 0
of O 0
bradyarrhythmia B-Disease 0
requiring O 0
a O 0
permanent O 0
pacemaker O 0
were O 0
matched O 0
( O 0
1 O 0
: O 0
4 O 0
) O 0
to O 0
1 O 0
, O 0
908 O 0
controls O 0
. O 0

Multivariable O 0
logistic O 0
regression O 0
was O 0
used O 0
to O 0
estimate O 0
the O 0
odds O 0
ratio O 0
( O 0
OR O 0
) O 0
of O 0
pacemaker O 0
insertion O 0
associated O 0
with O 0
amiodarone B-Chemical 0
use O 0
, O 0
controlling O 0
for O 0
baseline O 0
risk O 0
factors O 0
and O 0
exposure O 0
to O 0
sotalol B-Chemical 0
, O 0
Class O 0
I O 0
antiarrhythmic O 0
agents O 0
, O 0
beta O 0
- O 0
blockers O 0
, O 0
calcium B-Chemical 0
channel O 0
blockers O 0
, O 0
and O 0
digoxin B-Chemical 0
. O 0

RESULTS O 0
: O 0
amiodarone B-Chemical 0
use O 0
was O 0
associated O 0
with O 0
an O 0
increased O 0
risk O 0
of O 0
pacemaker O 0
insertion O 0
( O 0
OR O 0
: O 0
2 O 0
. O 0
14 O 0
, O 0
95 O 0
% O 0
confidence O 0
interval O 0
[ O 0
CI O 0
] O 0
: O 0
1 O 0
. O 0
30 O 0
to O 0
3 O 0
. O 0
54 O 0
) O 0
. O 0

This O 0
effect O 0
was O 0
modified O 0
by O 0
gender O 0
, O 0
with O 0
a O 0
greater O 0
risk O 0
in O 0
women O 0
versus O 0
men O 0
( O 0
OR O 0
: O 0
3 O 0
. O 0
86 O 0
, O 0
95 O 0
% O 0
CI O 0
: O 0
1 O 0
. O 0
70 O 0
to O 0
8 O 0
. O 0
75 O 0
vs O 0
. O 0
OR O 0
: O 0
1 O 0
. O 0
52 O 0
, O 0
95 O 0
% O 0
CI O 0
: O 0
0 O 0
. O 0
80 O 0
to O 0
2 O 0
. O 0
89 O 0
) O 0
. O 0

Digoxin B-Chemical 0
was O 0
the O 0
only O 0
other O 0
medication O 0
associated O 0
with O 0
an O 0
increased O 0
risk O 0
of O 0
pacemaker O 0
insertion O 0
( O 0
OR O 0
: O 0
1 O 0
. O 0
78 O 0
, O 0
95 O 0
% O 0
CI O 0
: O 0
1 O 0
. O 0
37 O 0
to O 0
2 O 0
. O 0
31 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
This O 0
study O 0
suggests O 0
that O 0
the O 0
use O 0
of O 0
amiodarone B-Chemical 0
in O 0
elderly O 0
patients O 0
with O 0
AF B-Disease 0
and O 0
a O 0
previous O 0
MI B-Disease 0
increases O 0
the O 0
risk O 0
of O 0
bradyarrhythmia B-Disease 0
requiring O 0
a O 0
permanent O 0
pacemaker O 0
. O 0

The O 0
finding O 0
of O 0
an O 0
augmented O 0
risk O 0
of O 0
pacemaker O 0
insertion O 0
in O 0
elderly O 0
women O 0
receiving O 0
amiodarone B-Chemical 0
requires O 0
further O 0
investigation O 0
. O 0

Indomethacin B-Chemical 0
- O 0
induced O 0
morphologic O 0
changes O 0
in O 0
the O 0
rat O 0
urinary O 0
bladder O 0
epithelium O 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
evaluate O 0
the O 0
morphologic O 0
changes O 0
in O 0
rat O 0
urothelium O 0
induced O 0
by O 0
indomethacin B-Chemical 0
. O 0

Nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
drug O 0
- O 0
induced O 0
cystitis B-Disease 0
is O 0
a O 0
poorly O 0
recognized O 0
and O 0
under O 0
- O 0
reported O 0
condition O 0
. O 0

In O 0
addition O 0
to O 0
tiaprofenic B-Chemical 0
acid I-Chemical 0
, O 0
indomethacin B-Chemical 0
has O 0
been O 0
reported O 0
to O 0
be O 0
associated O 0
with O 0
this O 0
condition O 0
. O 0

METHODS O 0
: O 0
Three O 0
groups O 0
were O 0
established O 0
: O 0
a O 0
control O 0
group O 0
( O 0
n O 0
= O 0
10 O 0
) O 0
, O 0
a O 0
high O 0
- O 0
dose O 0
group O 0
( O 0
n O 0
= O 0
10 O 0
) O 0
, O 0
treated O 0
with O 0
one O 0
intraperitoneal O 0
injection O 0
of O 0
indomethacin B-Chemical 0
20 O 0
mg O 0
/ O 0
kg O 0
, O 0
and O 0
a O 0
therapeutic O 0
dose O 0
group O 0
( O 0
n O 0
= O 0
10 O 0
) O 0
in O 0
which O 0
oral O 0
indomethacin B-Chemical 0
was O 0
administered O 0
3 O 0
. O 0
25 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
daily O 0
for O 0
3 O 0
weeks O 0
. O 0

The O 0
animals O 0
were O 0
then O 0
killed O 0
and O 0
the O 0
bladders O 0
removed O 0
for O 0
light O 0
and O 0
electron O 0
microscopic O 0
studies O 0
. O 0

RESULTS O 0
: O 0
The O 0
light O 0
microscopic O 0
findings O 0
showed O 0
some O 0
focal O 0
epithelial O 0
degeneration O 0
that O 0
was O 0
more O 0
prominent O 0
in O 0
the O 0
high O 0
- O 0
dose O 0
group O 0
. O 0

When O 0
compared O 0
with O 0
the O 0
control O 0
group O 0
, O 0
both O 0
indomethacin B-Chemical 0
groups O 0
revealed O 0
statistically O 0
increased O 0
numbers O 0
of O 0
mast O 0
cells O 0
in O 0
the O 0
mucosa O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
0001 O 0
) O 0
and O 0
penetration O 0
of O 0
lanthanum B-Chemical 0
nitrate I-Chemical 0
through O 0
intercellular O 0
areas O 0
of O 0
the O 0
epithelium O 0
. O 0

Furthermore O 0
, O 0
the O 0
difference O 0
in O 0
mast O 0
cell O 0
counts O 0
between O 0
the O 0
high O 0
and O 0
therapeutic O 0
dose O 0
groups O 0
was O 0
also O 0
statistically O 0
significant O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
0001 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Indomethacin B-Chemical 0
resulted O 0
in O 0
histopathologic O 0
findings O 0
typical O 0
of O 0
interstitial B-Disease 0
cystitis I-Disease 0
, O 0
such O 0
as O 0
leaky O 0
bladder O 0
epithelium O 0
and O 0
mucosal O 0
mastocytosis B-Disease 0
. O 0

The O 0
true O 0
incidence O 0
of O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
drug O 0
- O 0
induced O 0
cystitis B-Disease 0
in O 0
humans O 0
must O 0
be O 0
clarified O 0
by O 0
prospective O 0
clinical O 0
trials O 0
. O 0

An O 0
open O 0
- O 0
label O 0
phase O 0
II O 0
study O 0
of O 0
low O 0
- O 0
dose O 0
thalidomide B-Chemical 0
in O 0
androgen B-Chemical 0
- O 0
independent O 0
prostate B-Disease 0
cancer I-Disease 0
. O 0

The O 0
antiangiogenic O 0
effects O 0
of O 0
thalidomide B-Chemical 0
have O 0
been O 0
assessed O 0
in O 0
clinical O 0
trials O 0
in O 0
patients O 0
with O 0
various O 0
solid O 0
and O 0
haematological B-Disease 0
malignancies I-Disease 0
. O 0

Thalidomide B-Chemical 0
blocks O 0
the O 0
activity O 0
of O 0
angiogenic O 0
agents O 0
including O 0
bFGF O 0
, O 0
VEGF O 0
and O 0
IL O 0
- O 0
6 O 0
. O 0

We O 0
undertook O 0
an O 0
open O 0
- O 0
label O 0
study O 0
using O 0
thalidomide B-Chemical 0
100 O 0
mg O 0
once O 0
daily O 0
for O 0
up O 0
to O 0
6 O 0
months O 0
in O 0
20 O 0
men O 0
with O 0
androgen B-Chemical 0
- O 0
independent O 0
prostate B-Disease 0
cancer I-Disease 0
. O 0

The O 0
mean O 0
time O 0
of O 0
study O 0
was O 0
109 O 0
days O 0
( O 0
median O 0
107 O 0
, O 0
range O 0
4 O 0
- O 0
184 O 0
days O 0
) O 0
. O 0

Patients O 0
underwent O 0
regular O 0
measurement O 0
of O 0
prostate O 0
- O 0
specific O 0
antigen O 0
( O 0
PSA O 0
) O 0
, O 0
urea B-Chemical 0
and O 0
electrolytes O 0
, O 0
serum O 0
bFGF O 0
and O 0
VEGF O 0
. O 0

Three O 0
men O 0
( O 0
15 O 0
% O 0
) O 0
showed O 0
a O 0
decline O 0
in O 0
serum O 0
PSA O 0
of O 0
at O 0
least O 0
50 O 0
% O 0
, O 0
sustained O 0
throughout O 0
treatment O 0
. O 0

Of O 0
16 O 0
men O 0
treated O 0
for O 0
at O 0
least O 0
2 O 0
months O 0
, O 0
six O 0
( O 0
37 O 0
. O 0
5 O 0
% O 0
) O 0
showed O 0
a O 0
fall O 0
in O 0
absolute O 0
PSA O 0
by O 0
a O 0
median O 0
of O 0
48 O 0
% O 0
. O 0

Increasing O 0
levels O 0
of O 0
serum O 0
bFGF O 0
and O 0
VEGF O 0
were O 0
associated O 0
with O 0
progressive O 0
disease O 0
; O 0
five O 0
of O 0
six O 0
men O 0
who O 0
demonstrated O 0
a O 0
fall O 0
in O 0
PSA O 0
also O 0
showed O 0
a O 0
decline O 0
in O 0
bFGF O 0
and O 0
VEGF O 0
levels O 0
, O 0
and O 0
three O 0
of O 0
four O 0
men O 0
with O 0
a O 0
rising O 0
PSA O 0
showed O 0
an O 0
increase O 0
in O 0
both O 0
growth O 0
factors O 0
. O 0

Adverse O 0
effects O 0
included O 0
constipation B-Disease 0
, O 0
morning O 0
drowsiness B-Disease 0
, O 0
dizziness B-Disease 0
and O 0
rash B-Disease 0
, O 0
and O 0
resulted O 0
in O 0
withdrawal O 0
from O 0
the O 0
study O 0
by O 0
three O 0
men O 0
. O 0

Evidence O 0
of O 0
peripheral B-Disease 0
sensory I-Disease 0
neuropathy I-Disease 0
was O 0
found O 0
in O 0
nine O 0
of O 0
13 O 0
men O 0
before O 0
treatment O 0
. O 0

In O 0
the O 0
seven O 0
men O 0
who O 0
completed O 0
six O 0
months O 0
on O 0
thalidomide B-Chemical 0
, O 0
subclinical O 0
evidence O 0
of O 0
peripheral B-Disease 0
neuropathy I-Disease 0
was O 0
found O 0
in O 0
four O 0
before O 0
treatment O 0
, O 0
but O 0
in O 0
all O 0
seven O 0
at O 0
repeat O 0
testing O 0
. O 0

The O 0
findings O 0
indicate O 0
that O 0
thalidomide B-Chemical 0
may O 0
be O 0
an O 0
option O 0
for O 0
patients O 0
who O 0
have O 0
failed O 0
other O 0
forms O 0
of O 0
therapy O 0
, O 0
provided O 0
close O 0
follow O 0
- O 0
up O 0
is O 0
maintained O 0
for O 0
development O 0
of O 0
peripheral B-Disease 0
neuropathy I-Disease 0
. O 0

Central B-Disease 0
nervous I-Disease 0
system I-Disease 0
toxicity I-Disease 0
following O 0
the O 0
administration O 0
of O 0
levobupivacaine B-Chemical 0
for O 0
lumbar O 0
plexus O 0
block O 0
: O 0
A O 0
report O 0
of O 0
two O 0
cases O 0
. O 0

BACKGROUND O 0
AND O 0
OBJECTIVES O 0
: O 0
Central B-Disease 0
nervous I-Disease 0
system I-Disease 0
and I-Disease 0
cardiac I-Disease 0
toxicity I-Disease 0
following O 0
the O 0
administration O 0
of O 0
local O 0
anesthetics O 0
is O 0
a O 0
recognized O 0
complication O 0
of O 0
regional O 0
anesthesia O 0
. O 0

Levobupivacaine B-Chemical 0
, O 0
the O 0
pure O 0
S O 0
( O 0
- O 0
) O 0
enantiomer O 0
of O 0
bupivacaine B-Chemical 0
, O 0
was O 0
developed O 0
to O 0
improve O 0
the O 0
cardiac O 0
safety O 0
profile O 0
of O 0
bupivacaine B-Chemical 0
. O 0

We O 0
describe O 0
2 O 0
cases O 0
of O 0
grand B-Disease 0
mal I-Disease 0
seizures I-Disease 0
following O 0
accidental O 0
intravascular O 0
injection O 0
of O 0
levobupivacaine B-Chemical 0
. O 0

CASE O 0
REPORT O 0
: O 0
Two O 0
patients O 0
presenting O 0
for O 0
elective O 0
orthopedic O 0
surgery O 0
of O 0
the O 0
lower O 0
limb O 0
underwent O 0
blockade O 0
of O 0
the O 0
lumbar O 0
plexus O 0
via O 0
the O 0
posterior O 0
approach O 0
. O 0

Immediately O 0
after O 0
the O 0
administration O 0
of O 0
levobupivacaine B-Chemical 0
0 O 0
. O 0
5 O 0
% O 0
with O 0
epinephrine B-Chemical 0
2 O 0
. O 0
5 O 0
microgram O 0
/ O 0
mL O 0
, O 0
the O 0
patients O 0
developed O 0
grand B-Disease 0
mal I-Disease 0
seizures I-Disease 0
, O 0
despite O 0
negative O 0
aspiration O 0
for O 0
blood O 0
and O 0
no O 0
clinical O 0
signs O 0
of O 0
intravenous O 0
epinephrine B-Chemical 0
administration O 0
. O 0

The O 0
seizures B-Disease 0
were O 0
successfully O 0
treated O 0
with O 0
sodium B-Chemical 0
thiopental I-Chemical 0
in O 0
addition O 0
to O 0
succinylcholine B-Chemical 0
in O 0
1 O 0
patient O 0
. O 0

Neither O 0
patient O 0
developed O 0
signs O 0
of O 0
cardiovascular B-Disease 0
toxicity I-Disease 0
. O 0

Both O 0
patients O 0
were O 0
treated O 0
preoperatively O 0
with O 0
beta O 0
- O 0
adrenergic O 0
antagonist O 0
medications O 0
, O 0
which O 0
may O 0
have O 0
masked O 0
the O 0
cardiovascular O 0
signs O 0
of O 0
the O 0
unintentional O 0
intravascular O 0
administration O 0
of O 0
levobupivacaine B-Chemical 0
with O 0
epinephrine B-Chemical 0
. O 0

CONCLUSIONS O 0
: O 0
Although O 0
levobupivacaine B-Chemical 0
may O 0
have O 0
a O 0
safer O 0
cardiac B-Disease 0
toxicity I-Disease 0
profile O 0
than O 0
racemic O 0
bupivacaine B-Chemical 0
, O 0
if O 0
adequate O 0
amounts O 0
of O 0
levobupivacaine B-Chemical 0
reach O 0
the O 0
circulation O 0
, O 0
it O 0
will O 0
result O 0
in O 0
convulsions B-Disease 0
. O 0

Plasma O 0
concentrations O 0
sufficient O 0
to O 0
result O 0
in O 0
central B-Disease 0
nervous I-Disease 0
system I-Disease 0
toxicity I-Disease 0
did O 0
not O 0
produce O 0
manifestations O 0
of O 0
cardiac B-Disease 0
toxicity I-Disease 0
in O 0
these O 0
2 O 0
patients O 0
. O 0

Amiodarone B-Chemical 0
- O 0
induced O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
during O 0
bladder O 0
irrigation O 0
: O 0
an O 0
unusual O 0
presentation O 0
- O 0
- O 0
a O 0
case O 0
report O 0
. O 0

The O 0
authors O 0
present O 0
a O 0
case O 0
of O 0
early O 0
( O 0
within O 0
4 O 0
days O 0
) O 0
development O 0
of O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
( O 0
TdP B-Disease 0
) O 0
associated O 0
with O 0
oral O 0
amiodarone B-Chemical 0
therapy O 0
. O 0

Consistent O 0
with O 0
other O 0
reports O 0
this O 0
case O 0
of O 0
TdP B-Disease 0
occurred O 0
in O 0
the O 0
context O 0
of O 0
multiple O 0
exacerbating O 0
factors O 0
including O 0
hypokalemia B-Disease 0
and O 0
digoxin B-Chemical 0
excess O 0
. O 0

Transient O 0
prolongation O 0
of O 0
the O 0
QT O 0
during O 0
bladder O 0
irrigation O 0
prompted O 0
the O 0
episode O 0
of O 0
TdP B-Disease 0
. O 0

It O 0
is O 0
well O 0
known O 0
that O 0
bradycardia B-Disease 0
exacerbates O 0
acquired O 0
TdP B-Disease 0
. O 0

The O 0
authors O 0
speculate O 0
that O 0
the O 0
increased O 0
vagal O 0
tone O 0
during O 0
bladder O 0
irrigation O 0
, O 0
a O 0
vagal O 0
maneuver O 0
, O 0
in O 0
the O 0
context O 0
of O 0
amiodarone B-Chemical 0
therapy O 0
resulted O 0
in O 0
amiodarone B-Chemical 0
- O 0
induced O 0
proarrhythmia B-Disease 0
. O 0

In O 0
the O 0
absence O 0
of O 0
amiodarone B-Chemical 0
therapy O 0
, O 0
a O 0
second O 0
bladder O 0
irrigation O 0
did O 0
not O 0
induce O 0
TdP B-Disease 0
despite O 0
hypokalemia B-Disease 0
and O 0
hypomagnesemia B-Disease 0
. O 0

Anaesthetic O 0
complications O 0
associated O 0
with O 0
myotonia B-Disease 0
congenita I-Disease 0
: O 0
case O 0
study O 0
and O 0
comparison O 0
with O 0
other O 0
myotonic B-Disease 0
disorders I-Disease 0
. O 0

Myotonia B-Disease 0
congenita I-Disease 0
( O 0
MC B-Disease 0
) O 0
is O 0
caused O 0
by O 0
a O 0
defect O 0
in O 0
the O 0
skeletal O 0
muscle O 0
chloride B-Chemical 0
channel O 0
function O 0
, O 0
which O 0
may O 0
cause O 0
sustained B-Disease 0
membrane I-Disease 0
depolarisation I-Disease 0
. O 0

We O 0
describe O 0
a O 0
previously O 0
healthy O 0
32 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
who O 0
developed O 0
a O 0
life O 0
- O 0
threatening O 0
muscle B-Disease 0
spasm I-Disease 0
and O 0
secondary O 0
ventilation O 0
difficulties O 0
following O 0
a O 0
preoperative O 0
injection O 0
of O 0
suxamethonium B-Chemical 0
. O 0

The O 0
muscle B-Disease 0
spasms I-Disease 0
disappeared O 0
spontaneously O 0
and O 0
the O 0
surgery O 0
proceeded O 0
without O 0
further O 0
problems O 0
. O 0

When O 0
subsequently O 0
questioned O 0
, O 0
she O 0
reported O 0
minor O 0
symptoms O 0
suggesting O 0
a O 0
myotonic B-Disease 0
condition I-Disease 0
. O 0

Myotonia B-Disease 0
was O 0
found O 0
on O 0
clinical O 0
examination O 0
and O 0
EMG O 0
. O 0

The O 0
diagnosis O 0
MC B-Disease 0
was O 0
confirmed O 0
genetically O 0
. O 0

Neither O 0
the O 0
patient O 0
nor O 0
the O 0
anaesthetist O 0
were O 0
aware O 0
of O 0
the O 0
diagnosis O 0
before O 0
this O 0
potentially O 0
lethal O 0
complication O 0
occurred O 0
. O 0

We O 0
give O 0
a O 0
brief O 0
overview O 0
of O 0
ion B-Disease 0
channel I-Disease 0
disorders I-Disease 0
including O 0
malignant B-Disease 0
hyperthermia I-Disease 0
and O 0
their O 0
anaesthetic O 0
considerations O 0
. O 0

Respiratory O 0
pattern O 0
in O 0
a O 0
rat O 0
model O 0
of O 0
epilepsy B-Disease 0
. O 0

PURPOSE O 0
: O 0
Apnea B-Disease 0
is O 0
known O 0
to O 0
occur O 0
during O 0
seizures B-Disease 0
, O 0
but O 0
systematic O 0
studies O 0
of O 0
ictal O 0
respiratory O 0
changes O 0
in O 0
adults O 0
are O 0
few O 0
. O 0

Data O 0
regarding O 0
respiratory O 0
pattern O 0
defects O 0
during O 0
interictal O 0
periods O 0
also O 0
are O 0
scarce O 0
. O 0

Here O 0
we O 0
sought O 0
to O 0
generate O 0
information O 0
with O 0
regard O 0
to O 0
the O 0
interictal O 0
period O 0
in O 0
animals O 0
with O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
epilepsy B-Disease 0
. O 0

METHODS O 0
: O 0
Twelve O 0
rats O 0
( O 0
six O 0
chronically O 0
epileptic B-Disease 0
animals O 0
and O 0
six O 0
controls O 0
) O 0
were O 0
anesthetized O 0
, O 0
given O 0
tracheotomies O 0
, O 0
and O 0
subjected O 0
to O 0
hyperventilation B-Disease 0
or O 0
hypoventilation O 0
conditions O 0
. O 0

Breathing O 0
movements O 0
caused O 0
changes O 0
in O 0
thoracic O 0
volume O 0
and O 0
forced O 0
air O 0
to O 0
flow O 0
tidally O 0
through O 0
a O 0
pneumotachograph O 0
. O 0

This O 0
flow O 0
was O 0
measured O 0
by O 0
using O 0
a O 0
differential O 0
pressure O 0
transducer O 0
, O 0
passed O 0
through O 0
a O 0
polygraph O 0
, O 0
and O 0
from O 0
this O 0
to O 0
a O 0
computer O 0
with O 0
custom O 0
software O 0
that O 0
derived O 0
ventilation O 0
( O 0
VE O 0
) O 0
, O 0
tidal O 0
volume O 0
( O 0
VT O 0
) O 0
, O 0
inspiratory O 0
time O 0
( O 0
TI O 0
) O 0
, O 0
expiratory O 0
time O 0
( O 0
TE O 0
) O 0
, O 0
breathing O 0
frequency O 0
( O 0
f O 0
) O 0
, O 0
and O 0
mean O 0
inspiratory O 0
flow O 0
( O 0
VT O 0
/ O 0
TI O 0
) O 0
on O 0
a O 0
breath O 0
- O 0
by O 0
- O 0
breath O 0
basis O 0
. O 0

RESULTS O 0
: O 0
The O 0
hyperventilation B-Disease 0
maneuver O 0
caused O 0
a O 0
decrease O 0
in O 0
spontaneous O 0
ventilation O 0
in O 0
pilocarpine B-Chemical 0
- O 0
treated O 0
and O 0
control O 0
rats O 0
. O 0

Although O 0
VE O 0
had O 0
a O 0
similar O 0
decrease O 0
in O 0
both O 0
groups O 0
, O 0
in O 0
the O 0
epileptic B-Disease 0
group O 0
, O 0
the O 0
decrease O 0
in O 0
VE O 0
was O 0
due O 0
to O 0
a O 0
significant O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
increase O 0
in O 0
TE O 0
peak O 0
in O 0
relation O 0
to O 0
that O 0
of O 0
the O 0
control O 0
animals O 0
. O 0

The O 0
hypoventilation O 0
maneuver O 0
led O 0
to O 0
an O 0
increase O 0
in O 0
the O 0
arterial O 0
Paco2 O 0
, O 0
followed O 0
by O 0
an O 0
increase O 0
in O 0
VE O 0
. O 0

In O 0
the O 0
epileptic B-Disease 0
group O 0
, O 0
the O 0
increase O 0
in O 0
VE O 0
was O 0
mediated O 0
by O 0
a O 0
significant O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
decrease O 0
in O 0
TE O 0
peak O 0
compared O 0
with O 0
the O 0
control O 0
group O 0
. O 0

Systemic O 0
application O 0
of O 0
KCN O 0
, O 0
to O 0
evaluate O 0
the O 0
effects O 0
of O 0
peripheral O 0
chemoreception O 0
activation O 0
on O 0
ventilation O 0
, O 0
led O 0
to O 0
a O 0
similar O 0
increase O 0
in O 0
VE O 0
for O 0
both O 0
groups O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
data O 0
indicate O 0
that O 0
pilocarpine B-Chemical 0
- O 0
treated O 0
animals O 0
have O 0
an O 0
altered O 0
ability O 0
to O 0
react O 0
to O 0
( O 0
or O 0
compensate O 0
for O 0
) O 0
blood O 0
gas O 0
changes O 0
with O 0
changes O 0
in O 0
ventilation O 0
and O 0
suggest O 0
that O 0
it O 0
is O 0
centrally O 0
determined O 0
. O 0

We O 0
speculate O 0
on O 0
the O 0
possible O 0
relation O 0
of O 0
the O 0
current O 0
findings O 0
on O 0
treating O 0
different O 0
epilepsy B-Disease 0
- O 0
associated O 0
conditions O 0
. O 0

Fatal O 0
myeloencephalopathy B-Disease 0
due O 0
to O 0
intrathecal O 0
vincristine B-Chemical 0
administration O 0
. O 0

Vincristine B-Chemical 0
was O 0
accidentally O 0
given O 0
intrathecally O 0
to O 0
a O 0
child O 0
with O 0
leukaemia B-Disease 0
, O 0
producing O 0
sensory B-Disease 0
and I-Disease 0
motor I-Disease 0
dysfunction I-Disease 0
followed O 0
by O 0
encephalopathy B-Disease 0
and O 0
death O 0
. O 0

Separate O 0
times O 0
for O 0
administering O 0
vincristine B-Chemical 0
and O 0
intrathecal O 0
therapy O 0
is O 0
recommended O 0
. O 0

Progesterone B-Chemical 0
potentiation O 0
of O 0
bupivacaine B-Chemical 0
arrhythmogenicity O 0
in O 0
pentobarbital B-Chemical 0
- O 0
anesthetized O 0
rats O 0
and O 0
beating O 0
rat O 0
heart O 0
cell O 0
cultures O 0
. O 0

The O 0
effects O 0
of O 0
progesterone B-Chemical 0
treatment O 0
on O 0
bupivacaine B-Chemical 0
arrhythmogenicity O 0
in O 0
beating O 0
rat O 0
heart O 0
myocyte O 0
cultures O 0
and O 0
on O 0
anesthetized O 0
rats O 0
were O 0
determined O 0
. O 0

After O 0
determining O 0
the O 0
bupivacaine B-Chemical 0
AD50 O 0
( O 0
the O 0
concentration O 0
of O 0
bupivacaine B-Chemical 0
that O 0
caused O 0
50 O 0
% O 0
of O 0
all O 0
beating O 0
rat O 0
heart O 0
myocyte O 0
cultures O 0
to O 0
become O 0
arrhythmic B-Disease 0
) O 0
, O 0
we O 0
determined O 0
the O 0
effect O 0
of O 0
1 O 0
- O 0
hour O 0
progesterone B-Chemical 0
HCl B-Chemical 0
exposure O 0
on O 0
myocyte O 0
contractile O 0
rhythm O 0
. O 0

Each O 0
concentration O 0
of O 0
progesterone B-Chemical 0
( O 0
6 O 0
. O 0
25 O 0
, O 0
12 O 0
. O 0
5 O 0
, O 0
25 O 0
, O 0
and O 0
50 O 0
micrograms O 0
/ O 0
ml O 0
) O 0
caused O 0
a O 0
significant O 0
and O 0
concentration O 0
- O 0
dependent O 0
reduction O 0
in O 0
the O 0
AD50 O 0
for O 0
bupivacaine B-Chemical 0
. O 0

Estradiol B-Chemical 0
treatment O 0
also O 0
increased O 0
the O 0
arrhythmogenicity O 0
of O 0
bupivacaine B-Chemical 0
in O 0
myocyte O 0
cultures O 0
, O 0
but O 0
was O 0
only O 0
one O 0
fourth O 0
as O 0
potent O 0
as O 0
progesterone B-Chemical 0
. O 0

Neither O 0
progesterone B-Chemical 0
nor O 0
estradiol B-Chemical 0
effects O 0
on O 0
bupivacaine B-Chemical 0
arrhythmogenicity O 0
were O 0
potentiated O 0
by O 0
epinephrine B-Chemical 0
. O 0

Chronic O 0
progesterone B-Chemical 0
pretreatment O 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
for O 0
21 O 0
days O 0
) O 0
caused O 0
a O 0
significant O 0
increase O 0
in O 0
bupivacaine B-Chemical 0
arrhythmogenicity O 0
in O 0
intact O 0
pentobarbital B-Chemical 0
- O 0
anesthetized O 0
rats O 0
. O 0

There O 0
was O 0
a O 0
significant O 0
decrease O 0
in O 0
the O 0
time O 0
to O 0
onset O 0
of O 0
arrhythmia B-Disease 0
as O 0
compared O 0
with O 0
control O 0
nonprogesterone O 0
- O 0
treated O 0
rats O 0
( O 0
6 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
3 O 0
vs O 0
. O 0
30 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
5 O 0
min O 0
, O 0
mean O 0
+ O 0
/ O 0
- O 0
SE O 0
) O 0
. O 0

The O 0
results O 0
of O 0
this O 0
study O 0
indicate O 0
that O 0
progesterone B-Chemical 0
can O 0
potentiate O 0
bupivacaine B-Chemical 0
arrhythmogenicity O 0
both O 0
in O 0
vivo O 0
and O 0
in O 0
vitro O 0
. O 0

Potentiation O 0
of O 0
bupivacaine B-Chemical 0
arrhythmia B-Disease 0
in O 0
myocyte O 0
cultures O 0
suggests O 0
that O 0
this O 0
effect O 0
is O 0
at O 0
least O 0
partly O 0
mediated O 0
at O 0
the O 0
myocyte O 0
level O 0
. O 0

Increased O 0
serum O 0
soluble O 0
Fas O 0
in O 0
patients O 0
with O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
due O 0
to O 0
paracetamol B-Chemical 0
overdose B-Disease 0
. O 0

BACKGROUND O 0
/ O 0
AIMS O 0
: O 0
Experimental O 0
studies O 0
have O 0
suggested O 0
that O 0
apoptosis O 0
via O 0
the O 0
Fas O 0
/ O 0
Fas O 0
Ligand O 0
signaling O 0
system O 0
may O 0
play O 0
an O 0
important O 0
role O 0
in O 0
the O 0
development O 0
of O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
. O 0

The O 0
aim O 0
of O 0
the O 0
study O 0
was O 0
to O 0
investigate O 0
the O 0
soluble O 0
form O 0
of O 0
Fas O 0
in O 0
patients O 0
with O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
. O 0

METHODOLOGY O 0
: O 0
Serum O 0
levels O 0
of O 0
sFas O 0
( O 0
soluble O 0
Fas O 0
) O 0
were O 0
measured O 0
by O 0
ELISA O 0
in O 0
24 O 0
patients O 0
with O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
and O 0
10 O 0
normal O 0
control O 0
subjects O 0
. O 0

Serum O 0
levels O 0
of O 0
tumor B-Disease 0
necrosis B-Disease 0
factor O 0
- O 0
alpha O 0
and O 0
interferon O 0
- O 0
gamma O 0
were O 0
also O 0
determined O 0
by O 0
ELISA O 0
. O 0

RESULTS O 0
: O 0
Serum O 0
sFas O 0
was O 0
significantly O 0
increased O 0
in O 0
patients O 0
with O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
( O 0
median O 0
, O 0
26 O 0
. O 0
8 O 0
U O 0
/ O 0
mL O 0
; O 0
range O 0
, O 0
6 O 0
. O 0
9 O 0
- O 0
52 O 0
. O 0
7 O 0
U O 0
/ O 0
mL O 0
) O 0
compared O 0
to O 0
the O 0
normal O 0
controls O 0
( O 0
median O 0
, O 0
8 O 0
. O 0
6 O 0
U O 0
/ O 0
mL O 0
; O 0
range O 0
, O 0
6 O 0
. O 0
5 O 0
- O 0
12 O 0
. O 0
0 O 0
U O 0
/ O 0
mL O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
0001 O 0
) O 0
. O 0

Levels O 0
were O 0
significantly O 0
greater O 0
in O 0
patients O 0
with O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
due O 0
to O 0
paracetamol B-Chemical 0
overdose B-Disease 0
( O 0
median O 0
, O 0
28 O 0
. O 0
7 O 0
U O 0
/ O 0
mL O 0
; O 0
range O 0
, O 0
12 O 0
. O 0
8 O 0
- O 0
52 O 0
. O 0
7 O 0
U O 0
/ O 0
mL O 0
, O 0
n O 0
= O 0
17 O 0
) O 0
than O 0
those O 0
due O 0
to O 0
non O 0
- O 0
A O 0
to O 0
E O 0
hepatitis B-Disease 0
( O 0
median O 0
, O 0
12 O 0
. O 0
5 O 0
U O 0
/ O 0
mL O 0
; O 0
range O 0
, O 0
6 O 0
. O 0
9 O 0
- O 0
46 O 0
. O 0
0 O 0
U O 0
/ O 0
mL O 0
, O 0
n O 0
= O 0
7 O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

There O 0
was O 0
no O 0
relationship O 0
of O 0
sFas O 0
to O 0
eventual O 0
outcome O 0
in O 0
the O 0
patients O 0
. O 0

A O 0
significant O 0
correlation O 0
was O 0
observed O 0
between O 0
serum O 0
sFas O 0
levels O 0
and O 0
aspartate B-Chemical 0
aminotransferase O 0
( O 0
r O 0
= O 0
0 O 0
. O 0
613 O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
increased O 0
concentration O 0
of O 0
sFas O 0
in O 0
serum O 0
of O 0
patients O 0
with O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
may O 0
reflect O 0
activation O 0
of O 0
Fas O 0
- O 0
mediated O 0
apoptosis O 0
in O 0
the O 0
liver O 0
and O 0
this O 0
together O 0
with O 0
increased O 0
tumor B-Disease 0
necrosis B-Disease 0
factor O 0
- O 0
alpha O 0
may O 0
be O 0
an O 0
important O 0
factor O 0
in O 0
liver O 0
cell O 0
loss O 0
. O 0

Bilateral O 0
subthalamic O 0
nucleus O 0
stimulation O 0
for O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

High O 0
frequency O 0
stimulation O 0
of O 0
the O 0
subthalamic O 0
nucleus O 0
( O 0
STN O 0
) O 0
is O 0
known O 0
to O 0
ameliorate O 0
the O 0
signs O 0
and O 0
symptoms O 0
of O 0
advanced O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

AIM O 0
: O 0
We O 0
studied O 0
the O 0
effect O 0
of O 0
high O 0
frequency O 0
STN O 0
stimulation O 0
in O 0
23 O 0
patients O 0
. O 0

METHOD O 0
: O 0
Twenty O 0
- O 0
three O 0
patients O 0
suffering O 0
from O 0
severe O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
( O 0
Stages O 0
III O 0
- O 0
V O 0
on O 0
Hoehn O 0
and O 0
Yahr O 0
scale O 0
) O 0
and O 0
, O 0
particularly O 0
bradykinesia B-Disease 0
, O 0
rigidity B-Disease 0
, O 0
and O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
underwent O 0
bilateral O 0
implantation O 0
of O 0
electrodes O 0
in O 0
the O 0
STN O 0
. O 0

Preoperative O 0
and O 0
postoperative O 0
assessments O 0
of O 0
these O 0
patients O 0
at O 0
1 O 0
, O 0
3 O 0
, O 0
6 O 0
and O 0
12 O 0
months O 0
follow O 0
- O 0
up O 0
, O 0
in O 0
" O 0
on O 0
" O 0
and O 0
" O 0
off O 0
" O 0
drug O 0
conditions O 0
, O 0
was O 0
carried O 0
out O 0
using O 0
Unified O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
Disease I-Disease 0
Rating O 0
Scale O 0
, O 0
Hoehn O 0
and O 0
Yahr O 0
staging O 0
, O 0
England O 0
activities O 0
of O 0
daily O 0
living O 0
score O 0
and O 0
video O 0
recordings O 0
. O 0

RESULTS O 0
: O 0
After O 0
one O 0
year O 0
of O 0
electrical O 0
stimulation O 0
of O 0
the O 0
STN O 0
, O 0
the O 0
patients O 0
' O 0
scores O 0
for O 0
activities O 0
of O 0
daily O 0
living O 0
and O 0
motor O 0
examination O 0
scores O 0
( O 0
Unified O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
Disease I-Disease 0
Rating O 0
Scale O 0
parts O 0
II O 0
and O 0
III O 0
) O 0
off O 0
medication O 0
improved O 0
by O 0
62 O 0
% O 0
and O 0
61 O 0
% O 0
respectively O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
0005 O 0
) O 0
. O 0

The O 0
subscores O 0
for O 0
the O 0
akinesia B-Disease 0
, O 0
rigidity B-Disease 0
, O 0
tremor B-Disease 0
and O 0
gait O 0
also O 0
improved O 0
. O 0

( O 0
p O 0
< O 0
0 O 0
. O 0
0005 O 0
) O 0
. O 0

The O 0
average O 0
levodopa B-Chemical 0
dose O 0
decreased O 0
from O 0
813 O 0
mg O 0
to O 0
359 O 0
mg O 0
. O 0

The O 0
cognitive O 0
functions O 0
remained O 0
unchanged O 0
. O 0

Two O 0
patients O 0
developed O 0
device O 0
- O 0
related O 0
complications O 0
and O 0
two O 0
patients O 0
experienced O 0
abnormal O 0
weight O 0
gain O 0
. O 0

CONCLUSION O 0
: O 0
Bilateral O 0
subthalamic O 0
nucleus O 0
stimulation O 0
is O 0
an O 0
effective O 0
treatment O 0
for O 0
advanced O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

It O 0
reduces O 0
the O 0
severity O 0
of O 0
" O 0
off O 0
" O 0
phase O 0
symptoms O 0
, O 0
improves O 0
the O 0
axial O 0
symptoms O 0
and O 0
reduces O 0
levodopa B-Chemical 0
requirements O 0
. O 0

The O 0
reduction O 0
in O 0
the O 0
levodopa B-Chemical 0
dose O 0
is O 0
useful O 0
in O 0
controlling O 0
drug B-Disease 0
- I-Disease 0
induced I-Disease 0
dyskinesias I-Disease 0
. O 0

Acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
occurring O 0
during O 0
intravenous O 0
desferrioxamine B-Chemical 0
therapy O 0
: O 0
recovery O 0
after O 0
haemodialysis O 0
. O 0

A O 0
patient O 0
with O 0
transfusion O 0
- O 0
dependent O 0
thalassemia B-Disease 0
was O 0
undergoing O 0
home O 0
intravenous O 0
desferrioxamine B-Chemical 0
( O 0
DFX B-Chemical 0
) O 0
treatment O 0
by O 0
means O 0
of O 0
a O 0
totally O 0
implanted O 0
system O 0
because O 0
of O 0
his O 0
poor O 0
compliance O 0
with O 0
the O 0
nightly O 0
subcutaneous O 0
therapy O 0
. O 0

Due O 0
to O 0
an O 0
accidental O 0
malfunctioning O 0
of O 0
the O 0
infusion O 0
pump O 0
, O 0
the O 0
patient O 0
was O 0
inadvertently O 0
administered O 0
a O 0
toxic O 0
dosage O 0
of O 0
the O 0
drug O 0
which O 0
caused O 0
renal B-Disease 0
insufficiency I-Disease 0
. O 0

Given O 0
the O 0
progressive O 0
deterioration O 0
of O 0
the O 0
symptoms O 0
and O 0
of O 0
the O 0
laboratory O 0
values O 0
, O 0
despite O 0
adequate O 0
medical O 0
treatment O 0
, O 0
a O 0
decision O 0
was O 0
made O 0
to O 0
introduce O 0
haemodialytical O 0
therapy O 0
in O 0
order O 0
to O 0
remove O 0
the O 0
drug O 0
and O 0
therapy O 0
reduce O 0
the O 0
nephrotoxicity B-Disease 0
. O 0

From O 0
the O 0
results O 0
obtained O 0
, O 0
haemodialysis O 0
can O 0
therefore O 0
be O 0
suggested O 0
as O 0
a O 0
useful O 0
therapy O 0
in O 0
rare O 0
cases O 0
of O 0
progressive O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
caused O 0
by O 0
desferrioxamine B-Chemical 0
. O 0

Ocular O 0
motility O 0
changes O 0
after O 0
subtenon O 0
carboplatin B-Chemical 0
chemotherapy O 0
for O 0
retinoblastoma B-Disease 0
. O 0

BACKGROUND O 0
: O 0
Focal O 0
subtenon O 0
carboplatin B-Chemical 0
injections O 0
have O 0
recently O 0
been O 0
used O 0
as O 0
a O 0
presumably O 0
toxicity B-Disease 0
- O 0
free O 0
adjunct O 0
to O 0
systemic O 0
chemotherapy O 0
for O 0
intraocular O 0
retinoblastoma B-Disease 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
report O 0
our O 0
clinical O 0
experience O 0
with O 0
abnormal B-Disease 0
ocular I-Disease 0
motility I-Disease 0
in O 0
patients O 0
treated O 0
with O 0
subtenon O 0
carboplatin B-Chemical 0
chemotherapy O 0
. O 0

METHODS O 0
: O 0
We O 0
noted O 0
abnormal B-Disease 0
ocular I-Disease 0
motility I-Disease 0
in O 0
10 O 0
consecutive O 0
patients O 0
with O 0
retinoblastoma B-Disease 0
who O 0
had O 0
received O 0
subtenon O 0
carboplatin B-Chemical 0
. O 0

During O 0
ocular O 0
manipulation O 0
under O 0
general O 0
anesthesia O 0
, O 0
we O 0
assessed O 0
their O 0
eyes O 0
by O 0
forced O 0
duction O 0
testing O 0
, O 0
comparing O 0
ocular O 0
motility O 0
after O 0
tumor B-Disease 0
control O 0
with O 0
ocular O 0
motility O 0
at O 0
diagnosis O 0
. O 0

Eyes O 0
subsequently O 0
enucleated O 0
because O 0
of O 0
treatment O 0
failure O 0
( O 0
n O 0
= O 0
4 O 0
) O 0
were O 0
examined O 0
histologically O 0
. O 0

RESULTS O 0
: O 0
Limitation O 0
of O 0
ocular O 0
motility O 0
was O 0
detected O 0
in O 0
all O 0
12 O 0
eyes O 0
of O 0
10 O 0
patients O 0
treated O 0
for O 0
intraocular O 0
retinoblastoma B-Disease 0
with O 0
1 O 0
to O 0
6 O 0
injections O 0
of O 0
subtenon O 0
carboplatin B-Chemical 0
as O 0
part O 0
of O 0
multimodality O 0
therapy O 0
. O 0

Histopathological O 0
examination O 0
revealed O 0
many O 0
lipophages O 0
in O 0
the O 0
periorbital O 0
fat O 0
surrounding O 0
the O 0
optic O 0
nerve O 0
in O 0
1 O 0
eye O 0
, O 0
indicative O 0
of O 0
phagocytosis O 0
of O 0
previously O 0
existing O 0
fat O 0
cells O 0
and O 0
suggesting O 0
prior O 0
fat O 0
necrosis B-Disease 0
. O 0

The O 0
enucleations O 0
were O 0
technically O 0
difficult O 0
and O 0
hazardous O 0
for O 0
globe O 0
rupture B-Disease 0
because O 0
of O 0
extensive O 0
orbital O 0
soft O 0
tissue O 0
adhesions O 0
. O 0

CONCLUSIONS O 0
: O 0
Subtenon O 0
carboplatin B-Chemical 0
chemotherapy O 0
is O 0
associated O 0
with O 0
significant O 0
fibrosis B-Disease 0
of O 0
orbital O 0
soft O 0
tissues O 0
, O 0
leading O 0
to O 0
mechanical O 0
restriction O 0
of O 0
eye O 0
movements O 0
and O 0
making O 0
subsequent O 0
enucleation O 0
difficult O 0
. O 0

Subtenon O 0
carboplatin B-Chemical 0
is O 0
not O 0
free O 0
of O 0
toxicity B-Disease 0
, O 0
and O 0
its O 0
use O 0
is O 0
best O 0
restricted O 0
to O 0
specific O 0
indications O 0
. O 0

Ethambutol B-Chemical 0
and O 0
optic B-Disease 0
neuropathy I-Disease 0
. O 0

PURPOSE O 0
: O 0
To O 0
demonstrate O 0
the O 0
association O 0
between O 0
ethambutol B-Chemical 0
and O 0
optic B-Disease 0
neuropathy I-Disease 0
. O 0

METHOD O 0
: O 0
Thirteen O 0
patients O 0
who O 0
developed O 0
optic B-Disease 0
neuropathy I-Disease 0
after O 0
being O 0
treated O 0
with O 0
ethambutol B-Chemical 0
for O 0
tuberculosis B-Disease 0
of I-Disease 0
the I-Disease 0
lung I-Disease 0
or I-Disease 0
lymph I-Disease 0
node I-Disease 0
at O 0
Siriraj O 0
Hospital O 0
between O 0
1997 O 0
and O 0
2001 O 0
were O 0
retrospectively O 0
reviewed O 0
. O 0

The O 0
clinical O 0
characteristics O 0
and O 0
initial O 0
and O 0
final O 0
visual O 0
acuity O 0
were O 0
analyzed O 0
to O 0
determine O 0
visual O 0
outcome O 0
. O 0

RESULTS O 0
: O 0
All O 0
patients O 0
had O 0
optic B-Disease 0
neuropathy I-Disease 0
between O 0
1 O 0
to O 0
6 O 0
months O 0
( O 0
mean O 0
= O 0
2 O 0
. O 0
9 O 0
months O 0
) O 0
after O 0
starting O 0
ethambutol B-Chemical 0
therapy O 0
at O 0
a O 0
dosage O 0
ranging O 0
from O 0
13 O 0
to O 0
20 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
( O 0
mean O 0
= O 0
17 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
) O 0
. O 0

Seven O 0
( O 0
54 O 0
% O 0
) O 0
of O 0
the O 0
13 O 0
patients O 0
experienced O 0
visual O 0
recovery O 0
after O 0
stopping O 0
the O 0
drug O 0
. O 0

Of O 0
6 O 0
patients O 0
with O 0
irreversible O 0
visual B-Disease 0
impairment I-Disease 0
, O 0
4 O 0
patients O 0
had O 0
diabetes B-Disease 0
mellitus I-Disease 0
, O 0
glaucoma B-Disease 0
and O 0
a O 0
history O 0
of O 0
heavy O 0
smoking O 0
. O 0

CONCLUSION O 0
: O 0
Early O 0
recognition O 0
of O 0
optic B-Disease 0
neuropathy I-Disease 0
should O 0
be O 0
considered O 0
in O 0
patients O 0
with O 0
ethambutol B-Chemical 0
therapy O 0
. O 0

A O 0
low O 0
dose O 0
and O 0
prompt O 0
discontinuation O 0
of O 0
the O 0
drug O 0
is O 0
recommended O 0
particularly O 0
in O 0
individuals O 0
with O 0
diabetes B-Disease 0
mellitus I-Disease 0
, O 0
glaucoma B-Disease 0
or O 0
who O 0
are O 0
heavy O 0
smokers O 0
. O 0

Treatment O 0
of O 0
compensatory O 0
gustatory B-Disease 0
hyperhidrosis I-Disease 0
with O 0
topical O 0
glycopyrrolate B-Chemical 0
. O 0

Gustatory B-Disease 0
hyperhidrosis I-Disease 0
is O 0
facial O 0
sweating B-Disease 0
usually O 0
associated O 0
with O 0
the O 0
eating O 0
of O 0
hot O 0
spicy O 0
food O 0
or O 0
even O 0
smelling O 0
this O 0
food O 0
. O 0

Current O 0
options O 0
of O 0
treatment O 0
include O 0
oral O 0
anticholinergic O 0
drugs O 0
, O 0
the O 0
topical O 0
application O 0
of O 0
anticholinergics O 0
or O 0
aluminum B-Chemical 0
chloride I-Chemical 0
, O 0
and O 0
the O 0
injection O 0
of O 0
botulinum O 0
toxin O 0
. O 0

Thirteen O 0
patients O 0
have O 0
been O 0
treated O 0
to O 0
date O 0
with O 0
1 O 0
. O 0
5 O 0
% O 0
or O 0
2 O 0
% O 0
topical O 0
glycopyrrolate B-Chemical 0
. O 0

All O 0
patients O 0
had O 0
gustatory B-Disease 0
hyperhidrosis I-Disease 0
, O 0
which O 0
interfered O 0
with O 0
their O 0
social O 0
activities O 0
, O 0
after O 0
transthroacic O 0
endoscopic O 0
sympathectomy O 0
, O 0
and O 0
which O 0
was O 0
associated O 0
with O 0
compensatory O 0
focal O 0
hyperhidrosis B-Disease 0
. O 0

After O 0
applying O 0
topical O 0
glycopyrrolate B-Chemical 0
, O 0
the O 0
subjective O 0
effect O 0
was O 0
excellent O 0
( O 0
no O 0
sweating B-Disease 0
after O 0
eating O 0
hot O 0
spicy O 0
food O 0
) O 0
in O 0
10 O 0
patients O 0
( O 0
77 O 0
% O 0
) O 0
, O 0
and O 0
fair O 0
( O 0
clearly O 0
reduced O 0
sweating B-Disease 0
) O 0
in O 0
3 O 0
patients O 0
( O 0
23 O 0
% O 0
) O 0
. O 0

All O 0
had O 0
reported O 0
incidents O 0
of O 0
being O 0
very O 0
embarrassed O 0
whilst O 0
eating O 0
hot O 0
spicy O 0
foods O 0
. O 0

Adverse O 0
effects O 0
included O 0
a O 0
mildly O 0
dry B-Disease 0
mouth I-Disease 0
and O 0
a O 0
sore B-Disease 0
throat I-Disease 0
in O 0
2 O 0
patients O 0
( O 0
2 O 0
% O 0
glycopyrrolate B-Chemical 0
) O 0
, O 0
a O 0
light O 0
headache B-Disease 0
in O 0
1 O 0
patient O 0
( O 0
1 O 0
. O 0
5 O 0
% O 0
glycopyrrolate B-Chemical 0
) O 0
. O 0

The O 0
topical O 0
application O 0
of O 0
a O 0
glycopyrrolate B-Chemical 0
pad O 0
appeared O 0
to O 0
be O 0
safe O 0
, O 0
efficacious O 0
, O 0
well O 0
tolerated O 0
, O 0
and O 0
a O 0
convenient O 0
method O 0
of O 0
treatment O 0
for O 0
moderate O 0
to O 0
severe O 0
symptoms O 0
of O 0
gustatory B-Disease 0
hyperhidrosis I-Disease 0
in O 0
post O 0
transthoracic O 0
endoscopic O 0
sympathectomy O 0
or O 0
sympathicotomy O 0
patients O 0
, O 0
with O 0
few O 0
side O 0
effects O 0
. O 0

Neuroleptic B-Chemical 0
- O 0
associated O 0
hyperprolactinemia B-Disease 0
. O 0

Can O 0
it O 0
be O 0
treated O 0
with O 0
bromocriptine B-Chemical 0
? O 0

Six O 0
stable O 0
psychiatric O 0
outpatients O 0
with O 0
hyperprolactinemia B-Disease 0
and O 0
amenorrhea B-Disease 0
/ O 0
oligomenorrhea B-Disease 0
associated O 0
with O 0
their O 0
neuroleptic B-Chemical 0
medications I-Chemical 0
were O 0
treated O 0
with O 0
bromocriptine B-Chemical 0
. O 0

Daily O 0
dosages O 0
of O 0
5 O 0
- O 0
10 O 0
mg O 0
corrected O 0
the O 0
hyperprolactinemia B-Disease 0
and O 0
restored O 0
menstruation O 0
in O 0
four O 0
of O 0
the O 0
six O 0
patients O 0
. O 0

One O 0
woman O 0
, O 0
however O 0
, O 0
developed O 0
worsened O 0
psychiatric B-Disease 0
symptoms I-Disease 0
while O 0
taking O 0
bromocriptine B-Chemical 0
, O 0
and O 0
it O 0
was O 0
discontinued O 0
. O 0

Thus O 0
, O 0
three O 0
of O 0
six O 0
patients O 0
had O 0
their O 0
menstrual O 0
irregularity O 0
successfully O 0
corrected O 0
with O 0
bromocriptine B-Chemical 0
. O 0

This O 0
suggests O 0
that O 0
bromocriptine B-Chemical 0
should O 0
be O 0
further O 0
evaluated O 0
as O 0
potential O 0
therapy O 0
for O 0
neuroleptic B-Chemical 0
- O 0
associated O 0
hyperprolactinemia B-Disease 0
and O 0
amenorrhea B-Disease 0
/ O 0
galactorrhea B-Disease 0
. O 0

Ethacrynic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
and O 0
brain O 0
neurotransmitters O 0
in O 0
mice O 0
. O 0

Intracerebroventricular O 0
injection O 0
of O 0
ethacrynic B-Chemical 0
acid I-Chemical 0
( O 0
50 O 0
% O 0
convulsive B-Disease 0
dose O 0
; O 0
50 O 0
micrograms O 0
/ O 0
mouse O 0
) O 0
accelerated O 0
the O 0
synthesis O 0
/ O 0
turnover O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
hydroxytryptamine I-Chemical 0
( O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
) O 0
but O 0
suppressed O 0
the O 0
synthesis O 0
of O 0
gamma B-Chemical 0
- I-Chemical 0
aminobutyric I-Chemical 0
acid I-Chemical 0
and O 0
acetylcholine B-Chemical 0
in O 0
mouse O 0
brain O 0
. O 0

These O 0
effects O 0
were O 0
completely O 0
antagonized O 0
by O 0
pretreatment O 0
with O 0
a O 0
glutamate B-Chemical 0
/ O 0
N B-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
- I-Chemical 0
D I-Chemical 0
- I-Chemical 0
aspartate I-Chemical 0
antagonist O 0
, O 0
aminophosphonovaleric B-Chemical 0
acid I-Chemical 0
. O 0

In O 0
ethacrynic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
, O 0
these O 0
neurotransmitter O 0
systems O 0
may O 0
be O 0
differentially O 0
modulated O 0
, O 0
probably O 0
through O 0
activation O 0
of O 0
glutaminergic O 0
neurons O 0
in O 0
the O 0
brain O 0
. O 0

Pharmacology O 0
of O 0
gamma B-Chemical 0
- I-Chemical 0
aminobutyric I-Chemical 0
acidA I-Chemical 0
receptor O 0
complex O 0
after O 0
the O 0
in O 0
vivo O 0
administration O 0
of O 0
the O 0
anxioselective O 0
and O 0
anticonvulsant O 0
beta B-Chemical 0
- I-Chemical 0
carboline I-Chemical 0
derivative O 0
abecarnil B-Chemical 0
. O 0

In O 0
rodents O 0
, O 0
the O 0
effect O 0
of O 0
the O 0
beta B-Chemical 0
- I-Chemical 0
carboline I-Chemical 0
derivative O 0
isopropyl B-Chemical 0
- I-Chemical 0
6 I-Chemical 0
- I-Chemical 0
benzyloxy I-Chemical 0
- I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
methoxymethyl I-Chemical 0
- I-Chemical 0
beta I-Chemical 0
- I-Chemical 0
carboline I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
carboxylate I-Chemical 0
( O 0
abecarrnil B-Chemical 0
) O 0
, O 0
a O 0
new O 0
ligand O 0
for O 0
benzodiazepine B-Chemical 0
receptors O 0
possessing O 0
anxiolytic O 0
and O 0
anticonvulsant O 0
properties O 0
, O 0
was O 0
evaluated O 0
on O 0
the O 0
function O 0
of O 0
central O 0
gamma B-Chemical 0
- I-Chemical 0
aminobutyric I-Chemical 0
acid I-Chemical 0
( O 0
GABA B-Chemical 0
) O 0
A O 0
receptor O 0
complex O 0
, O 0
both O 0
in O 0
vitro O 0
and O 0
in O 0
vivo O 0
. O 0

Added O 0
in O 0
vitro O 0
to O 0
rat O 0
cortical O 0
membrane O 0
preparation O 0
, O 0
abecarnil B-Chemical 0
increased O 0
[ O 0
3H O 0
] O 0
GABA B-Chemical 0
binding O 0
, O 0
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muscimol B-Chemical 0
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36Cl O 0
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uptake O 0
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the O 0
binding O 0
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t B-Chemical 0
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[ I-Chemical 0
35S I-Chemical 0
] I-Chemical 0
butylbicyclophosphorothionate I-Chemical 0
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[ B-Chemical 0
35S I-Chemical 0
] I-Chemical 0
TBPS I-Chemical 0
) O 0
. O 0

These O 0
effects O 0
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similar O 0
to O 0
those O 0
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diazepam B-Chemical 0
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the O 0
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agonist O 0
Ro B-Chemical 0
16 I-Chemical 0
- I-Chemical 0
6028 I-Chemical 0
( O 0
tert B-Chemical 0
- I-Chemical 0
butyl I-Chemical 0
- I-Chemical 0
( I-Chemical 0
S I-Chemical 0
) I-Chemical 0
- I-Chemical 0
8 I-Chemical 0
- I-Chemical 0
bromo I-Chemical 0
- I-Chemical 0
11 I-Chemical 0
, I-Chemical 0
12 I-Chemical 0
, I-Chemical 0
13 I-Chemical 0
, I-Chemical 0
13a I-Chemical 0
- I-Chemical 0
tetrahydro I-Chemical 0
- I-Chemical 0
9 I-Chemical 0
- I-Chemical 0
oxo I-Chemical 0
- I-Chemical 0
9H I-Chemical 0
- I-Chemical 0
imidazo I-Chemical 0
[ I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
5 I-Chemical 0
- I-Chemical 0
a I-Chemical 0
] I-Chemical 0
- I-Chemical 0
pyrrolo I-Chemical 0
- I-Chemical 0
[ I-Chemical 0
2 I-Chemical 0
, I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
c I-Chemical 0
] I-Chemical 0
[ I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
4 I-Chemical 0
] I-Chemical 0
benzodiazepine I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
carboxylate I-Chemical 0
) O 0
showed O 0
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weak O 0
efficacy O 0
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After O 0
i O 0
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abecarnil B-Chemical 0
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decreased O 0
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0 O 0
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binding O 0
measured O 0
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Moreover O 0
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drugs O 0
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0 O 0
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activity O 0
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] I-Chemical 0
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binding O 0
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/ O 0
kg O 0
s O 0
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35S I-Chemical 0
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shock O 0
stress O 0
. O 0

To O 0
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pharmacological O 0
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, O 0
we O 0
studied O 0
the O 0
action O 0
of O 0
abecarnil B-Chemical 0
on O 0
[ B-Chemical 0
35S I-Chemical 0
] I-Chemical 0
TBPS I-Chemical 0
binding O 0
, O 0
exploratory O 0
motility O 0
and O 0
on O 0
isoniazid B-Chemical 0
- O 0
induced O 0
biochemical O 0
and O 0
pharmacological O 0
effects O 0
in O 0
mice O 0
. O 0

In O 0
these O 0
animals O 0
, O 0
abecarnil B-Chemical 0
produced O 0
a O 0
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dose O 0
- O 0
dependent O 0
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0 O 0
. O 0
05 O 0
- O 0
1 O 0
mg O 0
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i O 0
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p O 0
. O 0
) O 0
reduction O 0
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motor O 0
behavior O 0
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cortical O 0
[ O 0
35S O 0
] O 0
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. O 0

Moreover O 0
, O 0
0 O 0
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/ O 0
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this O 0
beta B-Chemical 0
- I-Chemical 0
carboline I-Chemical 0
reduced O 0
markedly O 0
the O 0
increase O 0
of O 0
[ B-Chemical 0
35S I-Chemical 0
] I-Chemical 0
TBPS I-Chemical 0
binding O 0
and O 0
the O 0
convulsions B-Disease 0
induced O 0
by O 0
isoniazid B-Chemical 0
( O 0
200 O 0
mg O 0
/ O 0
kg O 0
s O 0
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c O 0
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) O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Recurrent O 0
myocardial B-Disease 0
infarction I-Disease 0
in O 0
a O 0
postpartum O 0
patient O 0
receiving O 0
bromocriptine B-Chemical 0
. O 0

Myocardial B-Disease 0
infarction I-Disease 0
in O 0
puerperium O 0
is O 0
infrequently O 0
reported O 0
. O 0

Spasm B-Disease 0
, O 0
coronary O 0
dissection O 0
, O 0
or O 0
atheromatous O 0
etiology O 0
has O 0
been O 0
described O 0
. O 0

Bromocriptine B-Chemical 0
has O 0
been O 0
implicated O 0
in O 0
several O 0
previous O 0
case O 0
reports O 0
of O 0
myocardial B-Disease 0
infarction I-Disease 0
in O 0
the O 0
puerperium O 0
. O 0

Our O 0
case O 0
( O 0
including O 0
an O 0
inadvertent O 0
rechallenge O 0
) O 0
suggests O 0
such O 0
a O 0
relationship O 0
. O 0

Although O 0
generally O 0
regarded O 0
as O 0
" O 0
safe O 0
, O 0
" O 0
possible O 0
serious O 0
cardiac O 0
effects O 0
of O 0
bromocriptine B-Chemical 0
should O 0
be O 0
acknowledged O 0
. O 0

Asterixis B-Disease 0
induced O 0
by O 0
carbamazepine B-Chemical 0
therapy O 0
. O 0

There O 0
are O 0
very O 0
few O 0
reports O 0
about O 0
asterixis B-Disease 0
as O 0
a O 0
side O 0
effect O 0
of O 0
treatment O 0
with O 0
psychopharmacologic O 0
agents O 0
. O 0

In O 0
this O 0
report O 0
we O 0
present O 0
four O 0
patients O 0
treated O 0
with O 0
a O 0
combination O 0
of O 0
different O 0
psychotropic O 0
drugs O 0
, O 0
in O 0
whom O 0
asterixis B-Disease 0
was O 0
triggered O 0
either O 0
by O 0
adding O 0
carbamazepine B-Chemical 0
( O 0
CBZ B-Chemical 0
) O 0
to O 0
a O 0
treatment O 0
regimen O 0
, O 0
or O 0
by O 0
increasing O 0
its O 0
dosage O 0
. O 0

Neither O 0
dosage O 0
nor O 0
serum O 0
levels O 0
of O 0
CBZ B-Chemical 0
were O 0
in O 0
a O 0
higher O 0
range O 0
. O 0

We O 0
consider O 0
asterixis B-Disease 0
to O 0
be O 0
an O 0
easily O 0
overlooked O 0
sign O 0
of O 0
neurotoxicity B-Disease 0
, O 0
which O 0
may O 0
occur O 0
even O 0
at O 0
low O 0
or O 0
moderate O 0
dosage O 0
levels O 0
, O 0
if O 0
certain O 0
drugs O 0
as O 0
lithium B-Chemical 0
or O 0
clozapine B-Chemical 0
are O 0
used O 0
in O 0
combination O 0
with O 0
CBZ B-Chemical 0
. O 0

Pharmacodynamics O 0
of O 0
the O 0
hypotensive B-Disease 0
effect O 0
of O 0
levodopa B-Chemical 0
in O 0
parkinsonian B-Disease 0
patients O 0
. O 0

Blood O 0
pressure O 0
effects O 0
of O 0
i O 0
. O 0
v O 0
. O 0
levodopa B-Chemical 0
were O 0
examined O 0
in O 0
parkinsonian B-Disease 0
patients O 0
with O 0
stable O 0
and O 0
fluctuating O 0
responses O 0
to O 0
levodopa B-Chemical 0
. O 0

The O 0
magnitude O 0
of O 0
the O 0
hypotensive B-Disease 0
effect O 0
of O 0
levodopa B-Chemical 0
was O 0
concentration O 0
dependent O 0
and O 0
was O 0
fit O 0
to O 0
an O 0
Emax O 0
model O 0
in O 0
fluctuating O 0
responders O 0
. O 0

Stable O 0
responders O 0
demonstrated O 0
a O 0
small O 0
hypotensive B-Disease 0
response O 0
. O 0

Baseline O 0
blood O 0
pressures O 0
were O 0
higher O 0
in O 0
fluctuating O 0
patients O 0
; O 0
a O 0
higher O 0
baseline O 0
blood O 0
pressure O 0
correlated O 0
with O 0
greater O 0
hypotensive B-Disease 0
effects O 0
. O 0

Antiparkinsonian O 0
effects O 0
of O 0
levodopa B-Chemical 0
temporally O 0
correlated O 0
with O 0
blood O 0
pressure O 0
changes O 0
. O 0

Phenylalanine B-Chemical 0
, O 0
a O 0
large O 0
neutral O 0
amino B-Chemical 0
acid I-Chemical 0
( O 0
LNAA O 0
) O 0
competing O 0
with O 0
levodopa B-Chemical 0
for O 0
transport O 0
across O 0
the O 0
blood O 0
- O 0
brain O 0
barrier O 0
, O 0
reduced O 0
the O 0
hypotensive B-Disease 0
and O 0
antiparkinsonian O 0
effects O 0
of O 0
levodopa B-Chemical 0
. O 0

We O 0
conclude O 0
that O 0
levodopa B-Chemical 0
has O 0
a O 0
central O 0
hypotensive B-Disease 0
action O 0
that O 0
parallels O 0
the O 0
motor O 0
effects O 0
in O 0
fluctuating O 0
patients O 0
. O 0

The O 0
hypotensive B-Disease 0
effect O 0
appears O 0
to O 0
be O 0
related O 0
to O 0
the O 0
higher O 0
baseline O 0
blood O 0
pressure O 0
we O 0
observed O 0
in O 0
fluctuating O 0
patients O 0
relative O 0
to O 0
stable O 0
patients O 0
. O 0

Syndrome B-Disease 0
of I-Disease 0
inappropriate I-Disease 0
secretion I-Disease 0
of I-Disease 0
antidiuretic I-Disease 0
hormone I-Disease 0
after O 0
infusional O 0
vincristine B-Chemical 0
. O 0

A O 0
77 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
refractory O 0
multiple B-Disease 0
myeloma I-Disease 0
was O 0
treated O 0
with O 0
a O 0
4 O 0
- O 0
day O 0
continuous O 0
intravenous O 0
infusion O 0
of O 0
vincristine B-Chemical 0
and O 0
doxorubicin B-Chemical 0
and O 0
4 O 0
days O 0
of O 0
oral O 0
dexamethasone B-Chemical 0
. O 0

Nine O 0
days O 0
after O 0
her O 0
second O 0
cycle O 0
she O 0
presented O 0
with O 0
lethargy B-Disease 0
and O 0
weakness B-Disease 0
associated O 0
with O 0
hyponatremia B-Disease 0
. O 0

Evaluation O 0
revealed O 0
the O 0
syndrome B-Disease 0
of I-Disease 0
inappropriate I-Disease 0
secretion I-Disease 0
of I-Disease 0
antidiuretic I-Disease 0
hormone I-Disease 0
, O 0
which O 0
was O 0
attributed O 0
to O 0
the O 0
vincristine B-Chemical 0
infusion O 0
. O 0

After O 0
normal O 0
serum O 0
sodium B-Chemical 0
levels O 0
returned O 0
, O 0
further O 0
doxorubicin B-Chemical 0
and O 0
dexamethasone B-Chemical 0
chemotherapy O 0
without O 0
vincristine B-Chemical 0
did O 0
not O 0
produce O 0
this O 0
complication O 0
. O 0

Heart B-Disease 0
failure I-Disease 0
: O 0
to O 0
digitalise O 0
or O 0
not O 0
? O 0

The O 0
view O 0
against O 0
. O 0

Despite O 0
extensive O 0
clinical O 0
experience O 0
the O 0
role O 0
of O 0
digoxin B-Chemical 0
is O 0
still O 0
not O 0
well O 0
defined O 0
. O 0

In O 0
patients O 0
with O 0
atrial B-Disease 0
fibrillation I-Disease 0
digoxin B-Chemical 0
is O 0
beneficial O 0
for O 0
ventricular O 0
rate O 0
control O 0
. O 0

For O 0
patients O 0
in O 0
sinus O 0
rhythm O 0
and O 0
heart B-Disease 0
failure I-Disease 0
the O 0
situation O 0
is O 0
less O 0
clear O 0
. O 0

Digoxin B-Chemical 0
has O 0
a O 0
narrow O 0
therapeutic O 0
: O 0
toxic O 0
ratio O 0
and O 0
concentrations O 0
are O 0
affected O 0
by O 0
a O 0
number O 0
of O 0
drugs O 0
. O 0

Also O 0
, O 0
digoxin B-Chemical 0
has O 0
undesirable O 0
effects O 0
such O 0
as O 0
increasing O 0
peripheral O 0
resistance O 0
and O 0
myocardial O 0
demands O 0
, O 0
and O 0
causing O 0
arrhythmias B-Disease 0
. O 0

There O 0
is O 0
a O 0
paucity O 0
of O 0
data O 0
from O 0
well O 0
- O 0
designed O 0
trials O 0
. O 0

The O 0
trials O 0
that O 0
are O 0
available O 0
are O 0
generally O 0
small O 0
with O 0
limitations O 0
in O 0
design O 0
and O 0
these O 0
show O 0
variation O 0
in O 0
patient O 0
benefit O 0
. O 0

More O 0
convincing O 0
evidence O 0
is O 0
required O 0
showing O 0
that O 0
digoxin B-Chemical 0
improves O 0
symptoms O 0
or O 0
exercise O 0
capacity O 0
. O 0

Furthermore O 0
, O 0
no O 0
trial O 0
has O 0
had O 0
sufficient O 0
power O 0
to O 0
evaluate O 0
mortality O 0
. O 0

Pooled O 0
analysis O 0
of O 0
the O 0
effects O 0
of O 0
other O 0
inotropic O 0
drugs O 0
shows O 0
an O 0
excess O 0
mortality O 0
and O 0
there O 0
is O 0
a O 0
possibility O 0
that O 0
digoxin B-Chemical 0
may O 0
increase O 0
mortality O 0
after O 0
myocardial B-Disease 0
infarction I-Disease 0
( O 0
MI B-Disease 0
) O 0
. O 0

Angiotensin B-Chemical 0
- O 0
converting O 0
enzyme O 0
( O 0
ACE O 0
) O 0
inhibitors O 0
should O 0
be O 0
used O 0
first O 0
as O 0
they O 0
are O 0
safer O 0
, O 0
do O 0
not O 0
require O 0
blood O 0
level O 0
monitoring O 0
, O 0
modify O 0
progression O 0
of O 0
disease O 0
, O 0
relieve O 0
symptoms O 0
, O 0
improve O 0
exercise O 0
tolerance O 0
and O 0
reduce O 0
mortality O 0
. O 0

Caution O 0
should O 0
be O 0
exercised O 0
in O 0
using O 0
digoxin B-Chemical 0
until O 0
large O 0
mortality O 0
trials O 0
are O 0
completed O 0
showing O 0
either O 0
benefit O 0
or O 0
harm O 0
. O 0

Until O 0
then O 0
digoxin B-Chemical 0
should O 0
be O 0
considered O 0
a O 0
third O 0
- O 0
line O 0
therapy O 0
. O 0

Isradipine B-Chemical 0
treatment O 0
for O 0
hypertension B-Disease 0
in O 0
general O 0
practice O 0
in O 0
Hong O 0
Kong O 0
. O 0

A O 0
6 O 0
- O 0
week O 0
open O 0
study O 0
of O 0
the O 0
introduction O 0
of O 0
isradipine B-Chemical 0
treatment O 0
was O 0
conducted O 0
in O 0
general O 0
practice O 0
in O 0
Hong O 0
Kong O 0
. O 0

303 O 0
Chinese O 0
patients O 0
with O 0
mild O 0
to O 0
moderate O 0
hypertension B-Disease 0
entered O 0
the O 0
study O 0
. O 0

Side O 0
effects O 0
were O 0
reported O 0
in O 0
21 O 0
% O 0
of O 0
patients O 0
and O 0
caused O 0
withdrawal O 0
from O 0
the O 0
study O 0
in O 0
3 O 0
patients O 0
. O 0

The O 0
main O 0
side O 0
- O 0
effects O 0
were O 0
headache B-Disease 0
, O 0
dizziness B-Disease 0
, O 0
palpitation B-Disease 0
and O 0
flushing B-Disease 0
and O 0
these O 0
were O 0
not O 0
more O 0
frequent O 0
than O 0
reported O 0
in O 0
other O 0
studies O 0
with O 0
isradipine B-Chemical 0
or O 0
with O 0
placebo O 0
. O 0

Supine O 0
blood O 0
pressure O 0
was O 0
reduced O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
from O 0
170 O 0
+ O 0
/ O 0
- O 0
20 O 0
/ O 0
102 O 0
+ O 0
/ O 0
- O 0
6 O 0
mmHg O 0
to O 0
153 O 0
+ O 0
/ O 0
- O 0
19 O 0
/ O 0
92 O 0
+ O 0
/ O 0
- O 0
8 O 0
, O 0
147 O 0
+ O 0
/ O 0
- O 0
18 O 0
/ O 0
88 O 0
+ O 0
/ O 0
- O 0
7 O 0
and O 0
144 O 0
+ O 0
/ O 0
- O 0
14 O 0
/ O 0
87 O 0
+ O 0
/ O 0
- O 0
6 O 0
mmHg O 0
at O 0
2 O 0
, O 0
4 O 0
and O 0
6 O 0
weeks O 0
respectively O 0
in O 0
evaluable O 0
patients O 0
. O 0

Similar O 0
reductions O 0
occurred O 0
in O 0
standing O 0
blood O 0
pressure O 0
and O 0
there O 0
was O 0
no O 0
evidence O 0
of O 0
postural B-Disease 0
hypotension I-Disease 0
. O 0

Normalization O 0
and O 0
responder O 0
rates O 0
at O 0
6 O 0
weeks O 0
were O 0
86 O 0
% O 0
and O 0
69 O 0
% O 0
respectively O 0
. O 0

Dosage O 0
was O 0
increased O 0
from O 0
2 O 0
. O 0
5 O 0
mg O 0
b O 0
. O 0
d O 0
. O 0
to O 0
5 O 0
mg O 0
b O 0
. O 0
d O 0
. O 0
at O 0
4 O 0
weeks O 0
in O 0
patients O 0
with O 0
diastolic O 0
blood O 0
pressure O 0
greater O 0
than O 0
90 O 0
mmHg O 0
and O 0
their O 0
further O 0
response O 0
was O 0
greater O 0
than O 0
those O 0
remaining O 0
on O 0
2 O 0
. O 0
5 O 0
mg O 0
b O 0
. O 0
d O 0
. O 0

Pharmacological O 0
characteristics O 0
and O 0
side O 0
effects O 0
of O 0
a O 0
new O 0
galenic O 0
formulation O 0
of O 0
propofol B-Chemical 0
without O 0
soyabean O 0
oil O 0
. O 0

We O 0
compared O 0
the O 0
pharmacokinetics O 0
, O 0
pharmacodynamics O 0
and O 0
safety O 0
profile O 0
of O 0
a O 0
new O 0
galenic O 0
formulation O 0
of O 0
propofol B-Chemical 0
( O 0
AM149 O 0
1 O 0
% O 0
) O 0
, O 0
which O 0
does O 0
not O 0
contain O 0
soyabean O 0
oil O 0
, O 0
with O 0
a O 0
standard O 0
formulation O 0
of O 0
propofol B-Chemical 0
( O 0
Disoprivan B-Chemical 0
1 O 0
% O 0
) O 0
. O 0

In O 0
a O 0
randomised O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
cross O 0
- O 0
over O 0
study O 0
, O 0
30 O 0
healthy O 0
volunteers O 0
received O 0
a O 0
single O 0
intravenous O 0
bolus O 0
injection O 0
of O 0
2 O 0
. O 0
5 O 0
mg O 0
. O 0
kg O 0
- O 0
1 O 0
propofol B-Chemical 0
. O 0

Plasma O 0
propofol B-Chemical 0
levels O 0
were O 0
measured O 0
for O 0
48 O 0
h O 0
following O 0
drug O 0
administration O 0
and O 0
evaluated O 0
according O 0
to O 0
a O 0
three O 0
- O 0
compartment O 0
model O 0
. O 0

The O 0
pharmacodynamic O 0
parameters O 0
assessed O 0
included O 0
induction O 0
and O 0
emergence O 0
times O 0
, O 0
respiratory O 0
and O 0
cardiovascular O 0
effects O 0
, O 0
and O 0
pain B-Disease 0
on O 0
injection O 0
. O 0

Patients O 0
were O 0
monitored O 0
for O 0
side O 0
effects O 0
over O 0
48 O 0
h O 0
. O 0

Owing O 0
to O 0
a O 0
high O 0
incidence O 0
of O 0
thrombophlebitis B-Disease 0
, O 0
the O 0
study O 0
was O 0
terminated O 0
prematurely O 0
and O 0
only O 0
the O 0
data O 0
of O 0
the O 0
two O 0
parallel O 0
treatment O 0
groups O 0
( O 0
15 O 0
patients O 0
in O 0
each O 0
group O 0
) O 0
were O 0
analysed O 0
. O 0

Plasma O 0
concentrations O 0
did O 0
not O 0
differ O 0
significantly O 0
between O 0
the O 0
two O 0
formulations O 0
. O 0

Anaesthesia O 0
induction O 0
and O 0
emergence O 0
times O 0
, O 0
respiratory O 0
and O 0
cardiovascular O 0
variables O 0
showed O 0
no O 0
significant O 0
differences O 0
between O 0
the O 0
two O 0
treatment O 0
groups O 0
. O 0

Pain B-Disease 0
on O 0
injection O 0
( O 0
80 O 0
vs O 0
. O 0
20 O 0
% O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
and O 0
thrombophlebitis B-Disease 0
( O 0
93 O 0
. O 0
3 O 0
vs O 0
. O 0
6 O 0
. O 0
6 O 0
% O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
occurred O 0
more O 0
frequently O 0
with O 0
AM149 O 0
than O 0
with O 0
Disoprivan B-Chemical 0
. O 0

Although O 0
both O 0
formulations O 0
had O 0
similar O 0
pharmacokinetic O 0
and O 0
pharmacodynamic O 0
profiles O 0
the O 0
new O 0
formulation O 0
is O 0
not O 0
suitable O 0
for O 0
clinical O 0
use O 0
due O 0
to O 0
the O 0
high O 0
incidence O 0
of O 0
thrombophlebitis B-Disease 0
produced O 0
. O 0

Pure B-Disease 0
red I-Disease 0
cell I-Disease 0
aplasia I-Disease 0
, O 0
toxic B-Disease 0
dermatitis I-Disease 0
and O 0
lymphadenopathy B-Disease 0
in O 0
a O 0
patient O 0
taking O 0
diphenylhydantoin B-Chemical 0
. O 0

A O 0
patient O 0
taking O 0
diphenylhydantoin B-Chemical 0
for O 0
3 O 0
weeks O 0
developed O 0
a O 0
generalized O 0
skin B-Disease 0
rash I-Disease 0
, O 0
lymphadenopathy B-Disease 0
and O 0
pure B-Disease 0
red I-Disease 0
cell I-Disease 0
aplasia I-Disease 0
. O 0

After O 0
withdrawal O 0
of O 0
the O 0
pharmacon O 0
all O 0
symptoms O 0
disappeared O 0
spontaneously O 0
. O 0

Skin B-Disease 0
rash I-Disease 0
is O 0
a O 0
well O 0
- O 0
known O 0
complication O 0
of O 0
diphenylhydantoin B-Chemical 0
treatment O 0
as O 0
is O 0
benign O 0
and O 0
malignant O 0
lymphadenopathy B-Disease 0
. O 0

Pure B-Disease 0
red I-Disease 0
cell I-Disease 0
aplasia I-Disease 0
associated O 0
with O 0
diphenylhydantoin B-Chemical 0
medication O 0
has O 0
been O 0
reported O 0
in O 0
3 O 0
patients O 0
. O 0

The O 0
exact O 0
mechanism O 0
by O 0
which O 0
diphenylhydantoin B-Chemical 0
exerts O 0
its O 0
toxic O 0
effects O 0
is O 0
not O 0
known O 0
. O 0

In O 0
this O 0
patient O 0
the O 0
time O 0
relation O 0
between O 0
the O 0
ingestion O 0
of O 0
diphenylhydantoin B-Chemical 0
and O 0
the O 0
occurrence O 0
of O 0
the O 0
skin B-Disease 0
rash I-Disease 0
, O 0
lymphadenopathy B-Disease 0
and O 0
pure B-Disease 0
red I-Disease 0
cell I-Disease 0
aplasia I-Disease 0
is O 0
very O 0
suggestive O 0
of O 0
a O 0
direct O 0
connection O 0
. O 0

Vinorelbine B-Chemical 0
- O 0
related O 0
cardiac O 0
events O 0
: O 0
a O 0
meta O 0
- O 0
analysis O 0
of O 0
randomized O 0
clinical O 0
trials O 0
. O 0

Several O 0
cases O 0
of O 0
cardiac O 0
adverse O 0
reactions O 0
related O 0
to O 0
vinorelbine B-Chemical 0
( O 0
VNR B-Chemical 0
) O 0
have O 0
been O 0
reported O 0
in O 0
the O 0
literature O 0
. O 0

In O 0
order O 0
to O 0
quantify O 0
the O 0
incidence O 0
of O 0
these O 0
cardiac O 0
events O 0
, O 0
we O 0
performed O 0
a O 0
meta O 0
- O 0
analysis O 0
of O 0
clinical O 0
trials O 0
comparing O 0
VNR B-Chemical 0
with O 0
other O 0
chemotherapeutic O 0
agents O 0
in O 0
the O 0
treatment O 0
of O 0
various O 0
malignancies B-Disease 0
. O 0

Randomized O 0
clinical O 0
trials O 0
comparing O 0
VNR B-Chemical 0
with O 0
other O 0
drugs O 0
in O 0
the O 0
treatment O 0
of O 0
cancer B-Disease 0
were O 0
searched O 0
in O 0
Medline O 0
, O 0
Embase O 0
, O 0
Evidence O 0
- O 0
based O 0
Medicine O 0
Reviews O 0
databases O 0
and O 0
the O 0
Cochrane O 0
library O 0
from O 0
1987 O 0
to O 0
2002 O 0
. O 0

Outcomes O 0
of O 0
interest O 0
were O 0
severe O 0
cardiac O 0
events O 0
, O 0
toxic O 0
deaths O 0
and O 0
cardiac O 0
event O 0
- O 0
related O 0
deaths O 0
reported O 0
in O 0
each O 0
publication O 0
. O 0

We O 0
found O 0
19 O 0
trials O 0
, O 0
involving O 0
2441 O 0
patients O 0
treated O 0
by O 0
VNR B-Chemical 0
and O 0
2050 O 0
control O 0
patients O 0
. O 0

The O 0
incidence O 0
of O 0
cardiac O 0
events O 0
with O 0
VNR B-Chemical 0
was O 0
1 O 0
. O 0
19 O 0
% O 0
[ O 0
95 O 0
% O 0
confidence O 0
interval O 0
( O 0
CI O 0
) O 0
( O 0
0 O 0
. O 0
75 O 0
; O 0
1 O 0
. O 0
67 O 0
) O 0
] O 0
. O 0

There O 0
was O 0
no O 0
difference O 0
in O 0
the O 0
risk O 0
of O 0
cardiac O 0
events O 0
between O 0
VNR B-Chemical 0
and O 0
other O 0
drugs O 0
[ O 0
odds O 0
ratio O 0
: O 0
0 O 0
. O 0
92 O 0
, O 0
95 O 0
% O 0
CI O 0
( O 0
0 O 0
. O 0
54 O 0
; O 0
1 O 0
. O 0
55 O 0
) O 0
] O 0
. O 0

The O 0
risk O 0
of O 0
VNR B-Chemical 0
cardiac O 0
events O 0
was O 0
similar O 0
to O 0
vindesine B-Chemical 0
( O 0
VDS B-Chemical 0
) O 0
and O 0
other O 0
cardiotoxic B-Disease 0
drugs O 0
[ O 0
fluorouracil B-Chemical 0
, O 0
anthracyclines B-Chemical 0
, O 0
gemcitabine B-Chemical 0
( O 0
GEM B-Chemical 0
) O 0
em O 0
leader O 0
] O 0
. O 0

Even O 0
if O 0
it O 0
did O 0
not O 0
reach O 0
statistical O 0
significance O 0
because O 0
of O 0
a O 0
few O 0
number O 0
of O 0
cases O 0
, O 0
the O 0
risk O 0
was O 0
lower O 0
in O 0
trials O 0
excluding O 0
patients O 0
with O 0
cardiac O 0
history O 0
, O 0
and O 0
seemed O 0
to O 0
be O 0
higher O 0
in O 0
trials O 0
including O 0
patients O 0
with O 0
pre O 0
- O 0
existing O 0
cardiac B-Disease 0
diseases I-Disease 0
. O 0

Vinorelbine B-Chemical 0
- O 0
related O 0
cardiac O 0
events O 0
concern O 0
about O 0
1 O 0
% O 0
of O 0
treated O 0
patients O 0
in O 0
clinical O 0
trials O 0
. O 0

However O 0
, O 0
the O 0
risk O 0
associated O 0
with O 0
VNR B-Chemical 0
seems O 0
to O 0
be O 0
similar O 0
to O 0
that O 0
of O 0
other O 0
chemotherapeutic O 0
agents O 0
in O 0
the O 0
same O 0
indications O 0
. O 0

MRI O 0
findings O 0
of O 0
hypoxic O 0
cortical O 0
laminar O 0
necrosis B-Disease 0
in O 0
a O 0
child O 0
with O 0
hemolytic B-Disease 0
anemia I-Disease 0
crisis O 0
. O 0

We O 0
present O 0
magnetic O 0
resonance O 0
imaging O 0
findings O 0
of O 0
a O 0
5 O 0
- O 0
year O 0
- O 0
old O 0
girl O 0
who O 0
had O 0
a O 0
rapidly O 0
installing O 0
hemolytic B-Disease 0
anemia I-Disease 0
crisis O 0
induced O 0
by O 0
trimethoprim B-Chemical 0
- I-Chemical 0
sulfomethoxazole I-Chemical 0
, O 0
resulting O 0
in O 0
cerebral B-Disease 0
anoxia I-Disease 0
leading O 0
to O 0
permanent O 0
damage O 0
. O 0

Magnetic O 0
Resonance O 0
imaging O 0
revealed O 0
cortical O 0
laminar O 0
necrosis B-Disease 0
in O 0
arterial O 0
border O 0
zones O 0
in O 0
both O 0
cerebral O 0
hemispheres O 0
, O 0
ischemic O 0
changes O 0
in O 0
subcortical O 0
white O 0
matter O 0
of O 0
left O 0
cerebral O 0
hemisphere O 0
, O 0
and O 0
in O 0
the O 0
left O 0
putamen O 0
. O 0

Although O 0
cortical O 0
laminar O 0
necrosis B-Disease 0
is O 0
a O 0
classic O 0
entity O 0
in O 0
adulthood O 0
related O 0
to O 0
conditions O 0
of O 0
energy O 0
depletions O 0
, O 0
there O 0
are O 0
few O 0
reports O 0
available O 0
in O 0
children O 0
. O 0

A O 0
wide O 0
review O 0
of O 0
the O 0
literature O 0
is O 0
also O 0
presented O 0
. O 0

The O 0
natural O 0
history O 0
of O 0
Vigabatrin B-Chemical 0
associated O 0
visual B-Disease 0
field I-Disease 0
defects I-Disease 0
in O 0
patients O 0
electing O 0
to O 0
continue O 0
their O 0
medication O 0
. O 0

PURPOSE O 0
: O 0
To O 0
determine O 0
the O 0
natural O 0
history O 0
of O 0
visual B-Disease 0
field I-Disease 0
defects I-Disease 0
in O 0
a O 0
group O 0
of O 0
patients O 0
known O 0
to O 0
have O 0
Vigabatrin B-Chemical 0
- O 0
associated O 0
changes O 0
who O 0
elected O 0
to O 0
continue O 0
the O 0
medication O 0
because O 0
of O 0
good O 0
seizure B-Disease 0
control O 0
. O 0

METHODS O 0
: O 0
All O 0
patients O 0
taking O 0
Vigabatrin B-Chemical 0
alone O 0
or O 0
in O 0
combination O 0
with O 0
other O 0
antiepileptic O 0
drugs O 0
for O 0
at O 0
least O 0
5 O 0
years O 0
( O 0
range O 0
5 O 0
- O 0
12 O 0
years O 0
) O 0
were O 0
entered O 0
into O 0
a O 0
visual O 0
surveillance O 0
programme O 0
. O 0

Patients O 0
were O 0
followed O 0
up O 0
at O 0
6 O 0
- O 0
monthly O 0
intervals O 0
for O 0
not O 0
less O 0
than O 0
18 O 0
months O 0
( O 0
range O 0
18 O 0
- O 0
43 O 0
months O 0
) O 0
. O 0

In O 0
all O 0
, O 0
16 O 0
patients O 0
with O 0
unequivocal O 0
defects O 0
continued O 0
the O 0
medication O 0
. O 0

Following O 0
already O 0
published O 0
methodology O 0
( O 0
Eye O 0
2002 O 0
; O 0
16 O 0
; O 0
567 O 0
- O 0
571 O 0
) O 0
monocular O 0
mean O 0
radial O 0
degrees O 0
( O 0
MRDs O 0
) O 0
to O 0
the O 0
I O 0
/ O 0
4e O 0
isopter O 0
on O 0
Goldmann O 0
perimetry O 0
was O 0
calculated O 0
for O 0
the O 0
right O 0
eye O 0
at O 0
the O 0
time O 0
of O 0
discovery O 0
of O 0
a O 0
visual B-Disease 0
field I-Disease 0
defect I-Disease 0
and O 0
again O 0
after O 0
not O 0
less O 0
than O 0
18 O 0
months O 0
follow O 0
- O 0
up O 0
. O 0

RESULTS O 0
: O 0
Mean O 0
right O 0
eye O 0
MRD O 0
at O 0
presentation O 0
was O 0
36 O 0
. O 0
98 O 0
degrees O 0
( O 0
range O 0
22 O 0
. O 0
25 O 0
- O 0
51 O 0
. O 0
0 O 0
) O 0
, O 0
compared O 0
to O 0
38 O 0
. O 0
40 O 0
degrees O 0
( O 0
range O 0
22 O 0
. O 0
5 O 0
- O 0
49 O 0
. O 0
75 O 0
) O 0
after O 0
follow O 0
- O 0
up O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
338 O 0
unpaired O 0
t O 0
- O 0
test O 0
. O 0

Only O 0
one O 0
patient O 0
demonstrated O 0
a O 0
deterioration B-Disease 0
in I-Disease 0
visual I-Disease 0
field I-Disease 0
during O 0
the O 0
study O 0
period O 0
and O 0
discontinued O 0
treatment O 0
. O 0

CONCLUSION O 0
: O 0
Established O 0
visual B-Disease 0
field I-Disease 0
defects I-Disease 0
presumed O 0
to O 0
be O 0
due O 0
to O 0
Vigabatrin B-Chemical 0
therapy O 0
did O 0
not O 0
usually O 0
progress O 0
in O 0
spite O 0
of O 0
continuing O 0
use O 0
of O 0
the O 0
medication O 0
. O 0

These O 0
data O 0
give O 0
support O 0
to O 0
the O 0
hypothesis O 0
that O 0
the O 0
pathogenesis O 0
of O 0
Vigabatrin B-Chemical 0
- O 0
associated O 0
visual B-Disease 0
field I-Disease 0
defects I-Disease 0
may O 0
be O 0
an O 0
idiosyncratic O 0
adverse O 0
drug O 0
reaction O 0
rather O 0
than O 0
dose O 0
- O 0
dependent O 0
toxicity B-Disease 0
. O 0

Induction O 0
of O 0
rosaceiform O 0
dermatitis B-Disease 0
during O 0
treatment O 0
of O 0
facial B-Disease 0
inflammatory I-Disease 0
dermatoses I-Disease 0
with O 0
tacrolimus B-Chemical 0
ointment O 0
. O 0

BACKGROUND O 0
: O 0
Tacrolimus B-Chemical 0
ointment O 0
is O 0
increasingly O 0
used O 0
for O 0
anti O 0
- O 0
inflammatory O 0
treatment O 0
of O 0
sensitive O 0
areas O 0
such O 0
as O 0
the O 0
face O 0
, O 0
and O 0
recent O 0
observations O 0
indicate O 0
that O 0
the O 0
treatment O 0
is O 0
effective O 0
in O 0
steroid B-Chemical 0
- O 0
aggravated O 0
rosacea B-Disease 0
and O 0
perioral B-Disease 0
dermatitis I-Disease 0
. O 0

We O 0
report O 0
on O 0
rosaceiform O 0
dermatitis B-Disease 0
as O 0
a O 0
complication O 0
of O 0
treatment O 0
with O 0
tacrolimus B-Chemical 0
ointment O 0
. O 0

OBSERVATIONS O 0
: O 0
Six O 0
adult O 0
patients O 0
with O 0
inflammatory B-Disease 0
facial I-Disease 0
dermatoses I-Disease 0
were O 0
treated O 0
with O 0
tacrolimus B-Chemical 0
ointment O 0
because O 0
of O 0
the O 0
ineffectiveness O 0
of O 0
standard O 0
treatments O 0
. O 0

Within O 0
2 O 0
to O 0
3 O 0
weeks O 0
of O 0
initially O 0
effective O 0
and O 0
well O 0
- O 0
tolerated O 0
treatment O 0
, O 0
3 O 0
patients O 0
with O 0
a O 0
history O 0
of O 0
rosacea B-Disease 0
and O 0
1 O 0
with O 0
a O 0
history O 0
of O 0
acne B-Disease 0
experienced O 0
sudden O 0
worsening O 0
with O 0
pustular O 0
rosaceiform O 0
lesions O 0
. O 0

Biopsy O 0
revealed O 0
an O 0
abundance O 0
of O 0
Demodex O 0
mites O 0
in O 0
2 O 0
of O 0
these O 0
patients O 0
. O 0

In O 0
1 O 0
patient O 0
with O 0
eyelid O 0
eczema B-Disease 0
, O 0
rosaceiform O 0
periocular B-Disease 0
dermatitis I-Disease 0
gradually O 0
appeared O 0
after O 0
3 O 0
weeks O 0
of O 0
treatment O 0
. O 0

In O 0
1 O 0
patient O 0
with O 0
atopic B-Disease 0
dermatitis I-Disease 0
, O 0
telangiectatic O 0
and O 0
papular B-Disease 0
rosacea I-Disease 0
insidiously O 0
appeared O 0
after O 0
5 O 0
months O 0
of O 0
treatment O 0
. O 0

CONCLUSIONS O 0
: O 0
Our O 0
observations O 0
suggest O 0
that O 0
the O 0
spectrum O 0
of O 0
rosaceiform O 0
dermatitis B-Disease 0
as O 0
a O 0
complication O 0
of O 0
treatment O 0
with O 0
tacrolimus B-Chemical 0
ointment O 0
is O 0
heterogeneous O 0
. O 0

A O 0
variety O 0
of O 0
factors O 0
, O 0
such O 0
as O 0
vasoactive O 0
properties O 0
of O 0
tacrolimus B-Chemical 0
, O 0
proliferation O 0
of O 0
Demodex O 0
due O 0
to O 0
local O 0
immunosuppression O 0
, O 0
and O 0
the O 0
occlusive O 0
properties O 0
of O 0
the O 0
ointment O 0
, O 0
may O 0
be O 0
involved O 0
in O 0
the O 0
observed O 0
phenomena O 0
. O 0

Future O 0
studies O 0
are O 0
needed O 0
to O 0
identify O 0
individual O 0
risk O 0
factors O 0
. O 0

Intravascular O 0
hemolysis B-Disease 0
and O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
following O 0
intermittent O 0
rifampin B-Chemical 0
therapy O 0
. O 0

Renal B-Disease 0
failure I-Disease 0
is O 0
a O 0
rare O 0
complication O 0
associated O 0
with O 0
the O 0
use O 0
of O 0
rifampin B-Chemical 0
. O 0

Intravascular O 0
hemolysis B-Disease 0
leading O 0
to O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
following O 0
rifampin B-Chemical 0
therapy O 0
is O 0
extremely O 0
rare O 0
. O 0

Two O 0
patients O 0
with O 0
leprosy B-Disease 0
who O 0
developed O 0
hemolysis B-Disease 0
and O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
following O 0
rifampin B-Chemical 0
are O 0
reported O 0
. O 0

Structural O 0
abnormalities O 0
in O 0
the O 0
brains O 0
of O 0
human O 0
subjects O 0
who O 0
use O 0
methamphetamine B-Chemical 0
. O 0

We O 0
visualize O 0
, O 0
for O 0
the O 0
first O 0
time O 0
, O 0
the O 0
profile O 0
of O 0
structural B-Disease 0
deficits I-Disease 0
in I-Disease 0
the I-Disease 0
human I-Disease 0
brain I-Disease 0
associated O 0
with O 0
chronic O 0
methamphetamine B-Chemical 0
( O 0
MA B-Chemical 0
) O 0
abuse O 0
. O 0

Studies O 0
of O 0
human O 0
subjects O 0
who O 0
have O 0
used O 0
MA B-Chemical 0
chronically O 0
have O 0
revealed O 0
deficits O 0
in O 0
dopaminergic O 0
and O 0
serotonergic O 0
systems O 0
and O 0
cerebral O 0
metabolic B-Disease 0
abnormalities I-Disease 0
. O 0

Using O 0
magnetic O 0
resonance O 0
imaging O 0
( O 0
MRI O 0
) O 0
and O 0
new O 0
computational O 0
brain O 0
- O 0
mapping O 0
techniques O 0
, O 0
we O 0
determined O 0
the O 0
pattern O 0
of O 0
structural O 0
brain O 0
alterations O 0
associated O 0
with O 0
chronic O 0
MA B-Chemical 0
abuse O 0
in O 0
human O 0
subjects O 0
and O 0
related O 0
these O 0
deficits O 0
to O 0
cognitive B-Disease 0
impairment I-Disease 0
. O 0

We O 0
used O 0
high O 0
- O 0
resolution O 0
MRI O 0
and O 0
surface O 0
- O 0
based O 0
computational O 0
image O 0
analyses O 0
to O 0
map O 0
regional O 0
abnormalities B-Disease 0
in I-Disease 0
the I-Disease 0
cortex I-Disease 0
, I-Disease 0
hippocampus I-Disease 0
, I-Disease 0
white I-Disease 0
matter I-Disease 0
, I-Disease 0
and I-Disease 0
ventricles I-Disease 0
in O 0
22 O 0
human O 0
subjects O 0
who O 0
used O 0
MA B-Chemical 0
and O 0
21 O 0
age O 0
- O 0
matched O 0
, O 0
healthy O 0
controls O 0
. O 0

Cortical O 0
maps O 0
revealed O 0
severe O 0
gray O 0
- O 0
matter O 0
deficits O 0
in O 0
the O 0
cingulate O 0
, O 0
limbic O 0
, O 0
and O 0
paralimbic O 0
cortices O 0
of O 0
MA B-Chemical 0
abusers O 0
( O 0
averaging O 0
11 O 0
. O 0
3 O 0
% O 0
below O 0
control O 0
; O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

On O 0
average O 0
, O 0
MA B-Chemical 0
abusers O 0
had O 0
7 O 0
. O 0
8 O 0
% O 0
smaller O 0
hippocampal O 0
volumes O 0
than O 0
control O 0
subjects O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
; O 0
left O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
01 O 0
; O 0
right O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
and O 0
significant O 0
white O 0
- O 0
matter O 0
hypertrophy B-Disease 0
( O 0
7 O 0
. O 0
0 O 0
% O 0
; O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Hippocampal O 0
deficits O 0
were O 0
mapped O 0
and O 0
correlated O 0
with O 0
memory O 0
performance O 0
on O 0
a O 0
word O 0
- O 0
recall O 0
test O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

MRI O 0
- O 0
based O 0
maps O 0
suggest O 0
that O 0
chronic O 0
methamphetamine B-Chemical 0
abuse O 0
causes O 0
a O 0
selective O 0
pattern O 0
of O 0
cerebral O 0
deterioration O 0
that O 0
contributes O 0
to O 0
impaired B-Disease 0
memory I-Disease 0
performance I-Disease 0
. O 0

MA B-Chemical 0
may O 0
selectively O 0
damage O 0
the O 0
medial O 0
temporal O 0
lobe O 0
and O 0
, O 0
consistent O 0
with O 0
metabolic O 0
studies O 0
, O 0
the O 0
cingulate O 0
- O 0
limbic O 0
cortex O 0
, O 0
inducing O 0
neuroadaptation O 0
, O 0
neuropil O 0
reduction O 0
, O 0
or O 0
cell O 0
death O 0
. O 0

Prominent O 0
white O 0
- O 0
matter O 0
hypertrophy B-Disease 0
may O 0
result O 0
from O 0
altered O 0
myelination O 0
and O 0
adaptive O 0
glial O 0
changes O 0
, O 0
including O 0
gliosis B-Disease 0
secondary O 0
to O 0
neuronal B-Disease 0
damage I-Disease 0
. O 0

These O 0
brain O 0
substrates O 0
may O 0
help O 0
account O 0
for O 0
the O 0
symptoms O 0
of O 0
MA B-Chemical 0
abuse O 0
, O 0
providing O 0
therapeutic O 0
targets O 0
for O 0
drug O 0
- O 0
induced O 0
brain B-Disease 0
injury I-Disease 0
. O 0

Disruption O 0
of O 0
hepatic O 0
lipid O 0
homeostasis O 0
in O 0
mice O 0
after O 0
amiodarone B-Chemical 0
treatment O 0
is O 0
associated O 0
with O 0
peroxisome O 0
proliferator O 0
- O 0
activated O 0
receptor O 0
- O 0
alpha O 0
target O 0
gene O 0
activation O 0
. O 0

Amiodarone B-Chemical 0
, O 0
an O 0
efficacious O 0
and O 0
widely O 0
used O 0
antiarrhythmic O 0
agent O 0
, O 0
has O 0
been O 0
reported O 0
to O 0
cause O 0
hepatotoxicity B-Disease 0
in O 0
some O 0
patients O 0
. O 0

To O 0
gain O 0
insight O 0
into O 0
the O 0
mechanism O 0
of O 0
this O 0
unwanted O 0
effect O 0
, O 0
mice O 0
were O 0
administered O 0
various O 0
doses O 0
of O 0
amiodarone B-Chemical 0
and O 0
examined O 0
for O 0
changes O 0
in O 0
hepatic O 0
histology O 0
and O 0
gene O 0
regulation O 0
. O 0

Amiodarone B-Chemical 0
induced O 0
hepatomegaly B-Disease 0
, O 0
hepatocyte O 0
microvesicular O 0
lipid O 0
accumulation O 0
, O 0
and O 0
a O 0
significant O 0
decrease O 0
in O 0
serum O 0
triglycerides B-Chemical 0
and O 0
glucose B-Chemical 0
. O 0

Northern O 0
blot O 0
analysis O 0
of O 0
hepatic O 0
RNA O 0
revealed O 0
a O 0
dose O 0
- O 0
dependent O 0
increase O 0
in O 0
the O 0
expression O 0
of O 0
a O 0
number O 0
of O 0
genes O 0
critical O 0
for O 0
fatty B-Chemical 0
acid I-Chemical 0
oxidation O 0
, O 0
lipoprotein O 0
assembly O 0
, O 0
and O 0
lipid O 0
transport O 0
. O 0

Many O 0
of O 0
these O 0
genes O 0
are O 0
regulated O 0
by O 0
the O 0
peroxisome O 0
proliferator O 0
- O 0
activated O 0
receptor O 0
- O 0
alpha O 0
( O 0
PPARalpha O 0
) O 0
, O 0
a O 0
ligand O 0
- O 0
activated O 0
nuclear O 0
hormone O 0
receptor O 0
transcription O 0
factor O 0
. O 0

The O 0
absence O 0
of O 0
induction O 0
of O 0
these O 0
genes O 0
as O 0
well O 0
as O 0
hepatomegaly B-Disease 0
in O 0
PPARalpha O 0
knockout O 0
[ O 0
PPARalpha O 0
- O 0
/ O 0
- O 0
] O 0
mice O 0
indicated O 0
that O 0
the O 0
effects O 0
of O 0
amiodarone B-Chemical 0
were O 0
dependent O 0
upon O 0
the O 0
presence O 0
of O 0
a O 0
functional O 0
PPARalpha O 0
gene O 0
. O 0

Compared O 0
to O 0
wild O 0
- O 0
type O 0
mice O 0
, O 0
treatment O 0
of O 0
PPARalpha O 0
- O 0
/ O 0
- O 0
mice O 0
with O 0
amiodarone B-Chemical 0
resulted O 0
in O 0
an O 0
increased O 0
rate O 0
and O 0
extent O 0
of O 0
total O 0
body O 0
weight B-Disease 0
loss I-Disease 0
. O 0

The O 0
inability O 0
of O 0
amiodarone B-Chemical 0
to O 0
directly O 0
activate O 0
either O 0
human O 0
or O 0
mouse O 0
PPARalpha O 0
transiently O 0
expressed O 0
in O 0
human O 0
HepG2 O 0
hepatoma B-Disease 0
cells O 0
indicates O 0
that O 0
the O 0
effects O 0
of O 0
amiodarone B-Chemical 0
on O 0
the O 0
function O 0
of O 0
this O 0
receptor O 0
were O 0
indirect O 0
. O 0

Based O 0
upon O 0
these O 0
results O 0
, O 0
we O 0
conclude O 0
that O 0
amiodarone B-Chemical 0
disrupts O 0
hepatic O 0
lipid O 0
homeostasis O 0
and O 0
that O 0
the O 0
increased O 0
expression O 0
of O 0
PPARalpha O 0
target O 0
genes O 0
is O 0
secondary O 0
to O 0
this O 0
toxic O 0
effect O 0
. O 0

These O 0
results O 0
provide O 0
important O 0
new O 0
mechanistic O 0
information O 0
regarding O 0
the O 0
hepatotoxic B-Disease 0
effects O 0
of O 0
amiodarone B-Chemical 0
and O 0
indicate O 0
that O 0
PPARalpha O 0
protects O 0
against O 0
amiodarone B-Chemical 0
- O 0
induced O 0
hepatotoxicity B-Disease 0
. O 0

Safety O 0
and O 0
compliance O 0
with O 0
once O 0
- O 0
daily O 0
niacin B-Chemical 0
extended I-Chemical 0
- I-Chemical 0
release I-Chemical 0
/ I-Chemical 0
lovastatin I-Chemical 0
as O 0
initial O 0
therapy O 0
in O 0
the O 0
Impact O 0
of O 0
Medical O 0
Subspecialty O 0
on O 0
Patient O 0
Compliance O 0
to O 0
Treatment O 0
( O 0
IMPACT O 0
) O 0
study O 0
. O 0

Niacin B-Chemical 0
extended I-Chemical 0
- I-Chemical 0
release I-Chemical 0
/ I-Chemical 0
lovastatin I-Chemical 0
is O 0
a O 0
new O 0
combination O 0
product O 0
approved O 0
for O 0
treatment O 0
of O 0
primary O 0
hypercholesterolemia B-Disease 0
and O 0
mixed O 0
dyslipidemia B-Disease 0
. O 0

This O 0
open O 0
- O 0
labeled O 0
, O 0
multicenter O 0
study O 0
evaluated O 0
the O 0
safety O 0
of O 0
bedtime O 0
niacin B-Chemical 0
extended I-Chemical 0
- I-Chemical 0
release I-Chemical 0
/ I-Chemical 0
lovastatin I-Chemical 0
when O 0
dosed O 0
as O 0
initial O 0
therapy O 0
and O 0
patient O 0
compliance O 0
to O 0
treatment O 0
in O 0
various O 0
clinical O 0
practice O 0
settings O 0
. O 0

A O 0
total O 0
of O 0
4 O 0
, O 0
499 O 0
patients O 0
with O 0
dyslipidemia B-Disease 0
requiring O 0
drug O 0
intervention O 0
was O 0
enrolled O 0
at O 0
1 O 0
, O 0
081 O 0
sites O 0
. O 0

Patients O 0
were O 0
treated O 0
with O 0
1 O 0
tablet O 0
( O 0
500 O 0
mg O 0
of O 0
niacin B-Chemical 0
extended O 0
- O 0
release O 0
/ O 0
20 O 0
mg O 0
of O 0
lovastatin B-Chemical 0
) O 0
once O 0
nightly O 0
for O 0
4 O 0
weeks O 0
and O 0
then O 0
2 O 0
tablets O 0
for O 0
8 O 0
weeks O 0
. O 0

Patients O 0
also O 0
received O 0
dietary O 0
counseling O 0
, O 0
educational O 0
materials O 0
, O 0
and O 0
reminders O 0
to O 0
call O 0
a O 0
toll O 0
- O 0
free O 0
number O 0
that O 0
provided O 0
further O 0
education O 0
about O 0
dyslipidemia B-Disease 0
and O 0
niacin B-Chemical 0
extended I-Chemical 0
- I-Chemical 0
release I-Chemical 0
/ I-Chemical 0
lovastatin I-Chemical 0
. O 0

Primary O 0
end O 0
points O 0
were O 0
study O 0
compliance O 0
, O 0
increases O 0
in O 0
liver O 0
transaminases O 0
to O 0
> O 0
3 O 0
times O 0
the O 0
upper O 0
limit O 0
of O 0
normal O 0
, O 0
and O 0
clinical O 0
myopathy B-Disease 0
. O 0

Final O 0
study O 0
status O 0
was O 0
available O 0
for O 0
4 O 0
, O 0
217 O 0
patients O 0
( O 0
94 O 0
% O 0
) O 0
. O 0

Compliance O 0
to O 0
niacin B-Chemical 0
extended I-Chemical 0
- I-Chemical 0
release I-Chemical 0
/ I-Chemical 0
lovastatin I-Chemical 0
was O 0
77 O 0
% O 0
, O 0
with O 0
3 O 0
, O 0
245 O 0
patients O 0
completing O 0
the O 0
study O 0
. O 0

Patients O 0
in O 0
the O 0
southeast O 0
and O 0
those O 0
enrolled O 0
by O 0
endocrinologists O 0
had O 0
the O 0
lowest O 0
compliance O 0
and O 0
highest O 0
adverse O 0
event O 0
rates O 0
. O 0

Flushing B-Disease 0
was O 0
the O 0
most O 0
common O 0
adverse O 0
event O 0
, O 0
reported O 0
by O 0
18 O 0
% O 0
of O 0
patients O 0
and O 0
leading O 0
to O 0
discontinuation O 0
by O 0
6 O 0
% O 0
. O 0

Incidence O 0
of O 0
increased O 0
aspartate B-Chemical 0
aminotransferase O 0
and O 0
/ O 0
or O 0
alanine B-Chemical 0
aminotransferase O 0
> O 0
3 O 0
times O 0
the O 0
upper O 0
limit O 0
of O 0
normal O 0
was O 0
< O 0
0 O 0
. O 0
3 O 0
% O 0
. O 0

An O 0
increase O 0
of O 0
creatine B-Chemical 0
phosphokinase O 0
to O 0
> O 0
5 O 0
times O 0
the O 0
upper O 0
limit O 0
of O 0
normal O 0
occurred O 0
in O 0
0 O 0
. O 0
24 O 0
% O 0
of O 0
patients O 0
, O 0
and O 0
no O 0
cases O 0
of O 0
drug O 0
- O 0
induced O 0
myopathy B-Disease 0
were O 0
observed O 0
. O 0

Niacin B-Chemical 0
extended I-Chemical 0
- I-Chemical 0
release I-Chemical 0
/ I-Chemical 0
lovastatin I-Chemical 0
1 O 0
, O 0
000 O 0
/ O 0
40 O 0
mg O 0
, O 0
dosed O 0
as O 0
initial O 0
therapy O 0
, O 0
was O 0
associated O 0
with O 0
good O 0
compliance O 0
and O 0
safety O 0
and O 0
had O 0
very O 0
low O 0
incidences O 0
of O 0
increased O 0
liver O 0
and O 0
muscle O 0
enzymes O 0
. O 0

Protective O 0
effect O 0
of O 0
Terminalia B-Chemical 0
chebula I-Chemical 0
against O 0
experimental O 0
myocardial B-Disease 0
injury I-Disease 0
induced O 0
by O 0
isoproterenol B-Chemical 0
. O 0

Cardioprotective O 0
effect O 0
of O 0
ethanolic B-Chemical 0
extract I-Chemical 0
of I-Chemical 0
Terminalia I-Chemical 0
chebula I-Chemical 0
fruits I-Chemical 0
( O 0
500 O 0
mg O 0
/ O 0
kg O 0
body O 0
wt O 0
) O 0
was O 0
examined O 0
in O 0
isoproterenol B-Chemical 0
( O 0
200 O 0
mg O 0
/ O 0
kg O 0
body O 0
wt O 0
) O 0
induced O 0
myocardial B-Disease 0
damage I-Disease 0
in O 0
rats O 0
. O 0

In O 0
isoproterenol B-Chemical 0
administered O 0
rats O 0
, O 0
the O 0
level O 0
of O 0
lipid O 0
peroxides B-Chemical 0
increased O 0
significantly O 0
in O 0
the O 0
serum O 0
and O 0
heart O 0
. O 0

A O 0
significant O 0
decrease O 0
was O 0
observed O 0
in O 0
the O 0
activity O 0
of O 0
the O 0
myocardial O 0
marker O 0
enzymes O 0
with O 0
a O 0
concomitant O 0
increase O 0
in O 0
their O 0
activity O 0
in O 0
serum O 0
. O 0

Histopathological O 0
examination O 0
was O 0
carried O 0
out O 0
to O 0
confirm O 0
the O 0
myocardial O 0
necrosis B-Disease 0
. O 0

T B-Chemical 0
. I-Chemical 0
chebula I-Chemical 0
extract I-Chemical 0
pretreatment O 0
was O 0
found O 0
to O 0
ameliorate O 0
the O 0
effect O 0
of O 0
isoproterenol B-Chemical 0
on O 0
lipid O 0
peroxide B-Chemical 0
formation O 0
and O 0
retained O 0
the O 0
activities O 0
of O 0
the O 0
diagnostic O 0
marker O 0
enzymes O 0
. O 0

A O 0
case O 0
of O 0
postoperative O 0
anxiety B-Disease 0
due O 0
to O 0
low O 0
dose O 0
droperidol B-Chemical 0
used O 0
with O 0
patient O 0
- O 0
controlled O 0
analgesia O 0
. O 0

A O 0
multiparous O 0
woman O 0
in O 0
good O 0
psychological O 0
health O 0
underwent O 0
urgent O 0
caesarean O 0
section O 0
in O 0
labour O 0
. O 0

Postoperatively O 0
, O 0
she O 0
was O 0
given O 0
a O 0
patient O 0
- O 0
controlled O 0
analgesia O 0
device O 0
delivering O 0
boluses O 0
of O 0
diamorphine B-Chemical 0
0 O 0
. O 0
5 O 0
mg O 0
and O 0
droperidol B-Chemical 0
0 O 0
. O 0
025 O 0
mg O 0
. O 0

Whilst O 0
using O 0
the O 0
device O 0
she O 0
gradually O 0
became O 0
anxious O 0
, O 0
the O 0
feeling O 0
worsening O 0
after O 0
each O 0
bolus O 0
. O 0

The O 0
diagnosis O 0
of O 0
droperidol B-Chemical 0
- O 0
induced O 0
psychological B-Disease 0
disturbance I-Disease 0
was O 0
not O 0
made O 0
straight O 0
away O 0
although O 0
on O 0
subsequent O 0
close O 0
questioning O 0
the O 0
patient O 0
gave O 0
a O 0
very O 0
clear O 0
history O 0
. O 0

After O 0
she O 0
had O 0
received O 0
a O 0
total O 0
of O 0
only O 0
0 O 0
. O 0
9 O 0
mg O 0
droperidol B-Chemical 0
, O 0
a O 0
syringe O 0
containing O 0
diamorphine B-Chemical 0
only O 0
was O 0
substituted O 0
and O 0
her O 0
unease O 0
resolved O 0
completely O 0
. O 0

We O 0
feel O 0
that O 0
, O 0
although O 0
the O 0
dramatic O 0
extrapyramidal O 0
side O 0
effects O 0
of O 0
dopaminergic O 0
antiemetics O 0
are O 0
well O 0
known O 0
, O 0
more O 0
subtle O 0
manifestations O 0
may O 0
easily O 0
be O 0
overlooked O 0
. O 0

Accurate O 0
patient O 0
history O 0
contributes O 0
to O 0
differentiating O 0
diabetes B-Disease 0
insipidus I-Disease 0
: O 0
a O 0
case O 0
study O 0
. O 0

This O 0
case O 0
study O 0
highlights O 0
the O 0
important O 0
contribution O 0
of O 0
nursing O 0
in O 0
obtaining O 0
an O 0
accurate O 0
health O 0
history O 0
. O 0

The O 0
case O 0
discussed O 0
herein O 0
initially O 0
appeared O 0
to O 0
be O 0
neurogenic B-Disease 0
diabetes I-Disease 0
insipidus I-Disease 0
( O 0
DI B-Disease 0
) O 0
secondary O 0
to O 0
a O 0
traumatic B-Disease 0
brain I-Disease 0
injury I-Disease 0
. O 0

The O 0
nursing O 0
staff O 0
, O 0
by O 0
reviewing O 0
the O 0
patient O 0
' O 0
s O 0
health O 0
history O 0
with O 0
his O 0
family O 0
, O 0
discovered O 0
a O 0
history O 0
of O 0
polydipsia B-Disease 0
and O 0
long O 0
- O 0
standing O 0
lithium B-Chemical 0
use O 0
. O 0

Lithium B-Chemical 0
is O 0
implicated O 0
in O 0
drug O 0
- O 0
induced O 0
nephrogenic B-Disease 0
DI I-Disease 0
, O 0
and O 0
because O 0
the O 0
patient O 0
had O 0
not O 0
received O 0
lithium B-Chemical 0
since O 0
being O 0
admitted O 0
to O 0
the O 0
hospital O 0
, O 0
his O 0
treatment O 0
changed O 0
to O 0
focus O 0
on O 0
nephrogenic B-Disease 0
DI I-Disease 0
. O 0

By O 0
combining O 0
information O 0
from O 0
the O 0
patient O 0
history O 0
, O 0
the O 0
physical O 0
examination O 0
, O 0
and O 0
radiologic O 0
and O 0
laboratory O 0
studies O 0
, O 0
the O 0
critical O 0
care O 0
team O 0
demonstrated O 0
that O 0
the O 0
patient O 0
had O 0
been O 0
self O 0
- O 0
treating O 0
his O 0
lithium B-Chemical 0
- O 0
induced O 0
nephrogenic B-Disease 0
DI I-Disease 0
and O 0
developed O 0
neurogenic B-Disease 0
DI I-Disease 0
secondary O 0
to O 0
brain B-Disease 0
trauma I-Disease 0
. O 0

Thus O 0
successful O 0
treatment O 0
required O 0
that O 0
nephrogenic O 0
and O 0
neurogenic B-Disease 0
DI I-Disease 0
be O 0
treated O 0
concomitantly O 0
. O 0

Factors O 0
contributing O 0
to O 0
ribavirin B-Chemical 0
- O 0
induced O 0
anemia B-Disease 0
. O 0

BACKGROUND O 0
AND O 0
AIM O 0
: O 0
Interferon B-Chemical 0
and O 0
ribavirin B-Chemical 0
combination O 0
therapy O 0
for O 0
chronic B-Disease 0
hepatitis I-Disease 0
C I-Disease 0
produces O 0
hemolytic B-Disease 0
anemia I-Disease 0
. O 0

This O 0
study O 0
was O 0
conducted O 0
to O 0
identify O 0
the O 0
factors O 0
contributing O 0
to O 0
ribavirin B-Chemical 0
- O 0
induced O 0
anemia B-Disease 0
. O 0

METHODS O 0
: O 0
Eighty O 0
- O 0
eight O 0
patients O 0
with O 0
chronic B-Disease 0
hepatitis I-Disease 0
C I-Disease 0
who O 0
received O 0
interferon B-Chemical 0
- I-Chemical 0
alpha I-Chemical 0
- I-Chemical 0
2b I-Chemical 0
at O 0
a O 0
dose O 0
of O 0
6 O 0
MU O 0
administered O 0
intramuscularly O 0
for O 0
24 O 0
weeks O 0
in O 0
combination O 0
with O 0
ribavirin B-Chemical 0
administered O 0
orally O 0
at O 0
a O 0
dose O 0
of O 0
600 O 0
mg O 0
or O 0
800 O 0
mg O 0
participated O 0
in O 0
the O 0
study O 0
. O 0

A O 0
hemoglobin O 0
concentration O 0
of O 0
< O 0
10 O 0
g O 0
/ O 0
dL O 0
was O 0
defined O 0
as O 0
ribavirin B-Chemical 0
- O 0
induced O 0
anemia B-Disease 0
. O 0

RESULTS O 0
: O 0
Ribavirin B-Chemical 0
- O 0
induced O 0
anemia B-Disease 0
occurred O 0
in O 0
18 O 0
( O 0
20 O 0
. O 0
5 O 0
% O 0
) O 0
patients O 0
during O 0
treatment O 0
. O 0

A O 0
2 O 0
g O 0
/ O 0
dL O 0
decrease O 0
in O 0
hemoglobin O 0
concentrations O 0
in O 0
patients O 0
with O 0
anemia B-Disease 0
was O 0
observed O 0
at O 0
week O 0
2 O 0
after O 0
the O 0
start O 0
of O 0
treatment O 0
. O 0

The O 0
hemoglobin O 0
concentration O 0
in O 0
patients O 0
with O 0
> O 0
or O 0
= O 0
2 O 0
g O 0
/ O 0
dL O 0
decrease O 0
at O 0
week O 0
2 O 0
was O 0
observed O 0
to O 0
be O 0
significantly O 0
lower O 0
even O 0
after O 0
week O 0
2 O 0
than O 0
in O 0
patients O 0
with O 0
< O 0
2 O 0
g O 0
/ O 0
dL O 0
decrease O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

A O 0
significant O 0
relationship O 0
was O 0
observed O 0
between O 0
the O 0
rate O 0
of O 0
reduction O 0
of O 0
hemoglobin O 0
concentrations O 0
at O 0
week O 0
2 O 0
and O 0
the O 0
severity O 0
of O 0
anemia B-Disease 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Such O 0
factors O 0
as O 0
sex O 0
( O 0
female O 0
) O 0
, O 0
age O 0
( O 0
> O 0
or O 0
= O 0
60 O 0
years O 0
old O 0
) O 0
, O 0
and O 0
the O 0
ribavirin B-Chemical 0
dose O 0
by O 0
body O 0
weight O 0
( O 0
12 O 0
mg O 0
/ O 0
kg O 0
or O 0
more O 0
) O 0
were O 0
significant O 0
by O 0
univariate O 0
analysis O 0
. O 0

CONCLUSIONS O 0
: O 0
Careful O 0
administration O 0
is O 0
necessary O 0
in O 0
patients O 0
> O 0
or O 0
= O 0
60 O 0
years O 0
old O 0
, O 0
in O 0
female O 0
patients O 0
, O 0
and O 0
in O 0
patients O 0
receiving O 0
a O 0
ribavirin B-Chemical 0
dose O 0
of O 0
12 O 0
mg O 0
/ O 0
kg O 0
or O 0
more O 0
. O 0

Patients O 0
who O 0
experience O 0
a O 0
fall O 0
in O 0
hemoglobin O 0
concentrations O 0
of O 0
2 O 0
g O 0
/ O 0
dL O 0
or O 0
more O 0
at O 0
week O 0
2 O 0
after O 0
the O 0
start O 0
of O 0
treatment O 0
should O 0
be O 0
monitored O 0
with O 0
particular O 0
care O 0
. O 0

Zidovudine B-Chemical 0
- O 0
induced O 0
hepatitis B-Disease 0
. O 0

A O 0
case O 0
of O 0
acute O 0
hepatitis B-Disease 0
induced O 0
by O 0
zidovudine B-Chemical 0
in O 0
a O 0
38 O 0
- O 0
year O 0
- O 0
old O 0
patient O 0
with O 0
AIDS B-Disease 0
is O 0
presented O 0
. O 0

The O 0
mechanism O 0
whereby O 0
the O 0
hepatitis B-Disease 0
was O 0
induced O 0
is O 0
not O 0
known O 0
. O 0

However O 0
, O 0
the O 0
patient O 0
tolerated O 0
well O 0
an O 0
alternative O 0
reverse O 0
transcriptase O 0
inhibitor O 0
, O 0
2 B-Chemical 0
' I-Chemical 0
3 I-Chemical 0
' I-Chemical 0
dideoxyinosine I-Chemical 0
. O 0

Physicians O 0
caring O 0
for O 0
patients O 0
with O 0
AIDS B-Disease 0
should O 0
be O 0
aware O 0
of O 0
this O 0
hitherto O 0
rarely O 0
reported O 0
complication O 0
. O 0

Oxidative O 0
damage O 0
precedes O 0
nitrative O 0
damage O 0
in O 0
adriamycin B-Chemical 0
- O 0
induced O 0
cardiac O 0
mitochondrial B-Disease 0
injury I-Disease 0
. O 0

The O 0
purpose O 0
of O 0
the O 0
present O 0
study O 0
was O 0
to O 0
determine O 0
if O 0
elevated O 0
reactive O 0
oxygen B-Chemical 0
( O 0
ROS O 0
) O 0
/ O 0
nitrogen B-Chemical 0
species O 0
( O 0
RNS O 0
) O 0
reported O 0
to O 0
be O 0
present O 0
in O 0
adriamycin B-Chemical 0
( O 0
ADR B-Chemical 0
) O 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
actually O 0
resulted O 0
in O 0
cardiomyocyte O 0
oxidative O 0
/ O 0
nitrative O 0
damage O 0
, O 0
and O 0
to O 0
quantitatively O 0
determine O 0
the O 0
time O 0
course O 0
and O 0
subcellular O 0
localization O 0
of O 0
these O 0
postulated O 0
damage O 0
products O 0
using O 0
an O 0
in O 0
vivo O 0
approach O 0
. O 0

B6C3 O 0
mice O 0
were O 0
treated O 0
with O 0
a O 0
single O 0
dose O 0
of O 0
20 O 0
mg O 0
/ O 0
kg O 0
ADR B-Chemical 0
. O 0

Ultrastructural O 0
damage O 0
and O 0
levels O 0
of O 0
4 B-Chemical 0
- I-Chemical 0
hydroxy I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
nonenal I-Chemical 0
( O 0
4HNE B-Chemical 0
) O 0
- O 0
protein O 0
adducts O 0
and O 0
3 B-Chemical 0
- I-Chemical 0
nitrotyrosine I-Chemical 0
( O 0
3NT B-Chemical 0
) O 0
were O 0
analyzed O 0
. O 0

Quantitative O 0
ultrastructural O 0
damage O 0
using O 0
computerized O 0
image O 0
techniques O 0
showed O 0
cardiomyocyte O 0
injury O 0
as O 0
early O 0
as O 0
3 O 0
hours O 0
, O 0
with O 0
mitochondria O 0
being O 0
the O 0
most O 0
extensively O 0
and O 0
progressively O 0
injured O 0
subcellular O 0
organelle O 0
. O 0

Analysis O 0
of O 0
4HNE B-Chemical 0
protein O 0
adducts O 0
by O 0
immunogold O 0
electron O 0
microscopy O 0
showed O 0
appearance O 0
of O 0
4HNE B-Chemical 0
protein O 0
adducts O 0
in O 0
mitochondria O 0
as O 0
early O 0
as O 0
3 O 0
hours O 0
, O 0
with O 0
a O 0
peak O 0
at O 0
6 O 0
hours O 0
and O 0
subsequent O 0
decline O 0
at O 0
24 O 0
hours O 0
. O 0

3NT B-Chemical 0
levels O 0
were O 0
significantly O 0
increased O 0
in O 0
all O 0
subcellular O 0
compartments O 0
at O 0
6 O 0
hours O 0
and O 0
subsequently O 0
declined O 0
at O 0
24 O 0
hours O 0
. O 0

Our O 0
data O 0
showed O 0
ADR B-Chemical 0
induced O 0
4HNE B-Chemical 0
- O 0
protein O 0
adducts O 0
in O 0
mitochondria O 0
at O 0
the O 0
same O 0
time O 0
point O 0
as O 0
when O 0
mitochondrial B-Disease 0
injury I-Disease 0
initially O 0
appeared O 0
. O 0

These O 0
results O 0
document O 0
for O 0
the O 0
first O 0
time O 0
in O 0
vivo O 0
that O 0
mitochondrial B-Disease 0
oxidative I-Disease 0
damage I-Disease 0
precedes O 0
nitrative O 0
damage O 0
. O 0

The O 0
progressive O 0
nature O 0
of O 0
mitochondrial B-Disease 0
injury I-Disease 0
suggests O 0
that O 0
mitochondria O 0
, O 0
not O 0
other O 0
subcellular O 0
organelles O 0
, O 0
are O 0
the O 0
major O 0
site O 0
of O 0
intracellular O 0
injury O 0
. O 0

Sotalol B-Chemical 0
- O 0
induced O 0
coronary B-Disease 0
spasm I-Disease 0
in O 0
a O 0
patient O 0
with O 0
dilated B-Disease 0
cardiomyopathy I-Disease 0
associated O 0
with O 0
sustained O 0
ventricular B-Disease 0
tachycardia I-Disease 0
. O 0

A O 0
54 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
severe O 0
left O 0
ventricular B-Disease 0
dysfunction I-Disease 0
due O 0
to O 0
dilated B-Disease 0
cardiomyopathy I-Disease 0
was O 0
referred O 0
to O 0
our O 0
hospital O 0
for O 0
symptomatic O 0
incessant O 0
sustained O 0
ventricular B-Disease 0
tachycardia I-Disease 0
( O 0
VT B-Disease 0
) O 0
. O 0

After O 0
the O 0
administration O 0
of O 0
nifekalant B-Chemical 0
hydrochloride I-Chemical 0
, O 0
sustained O 0
VT B-Disease 0
was O 0
terminated O 0
. O 0

An O 0
alternate O 0
class O 0
III O 0
agent O 0
, O 0
sotalol B-Chemical 0
, O 0
was O 0
also O 0
effective O 0
for O 0
the O 0
prevention O 0
of O 0
VT B-Disease 0
. O 0

However O 0
, O 0
one O 0
month O 0
after O 0
switching O 0
over O 0
nifekalant B-Chemical 0
to O 0
sotalol B-Chemical 0
, O 0
a O 0
short O 0
duration O 0
of O 0
ST O 0
elevation O 0
was O 0
documented O 0
in O 0
ECG O 0
monitoring O 0
at O 0
almost O 0
the O 0
same O 0
time O 0
for O 0
three O 0
consecutive O 0
days O 0
. O 0

ST O 0
elevation O 0
with O 0
chest O 0
discomfort O 0
disappeared O 0
since O 0
he O 0
began O 0
taking O 0
long O 0
- O 0
acting O 0
diltiazem B-Chemical 0
. O 0

Coronary B-Disease 0
vasospasm I-Disease 0
may O 0
be O 0
induced O 0
by O 0
the O 0
non O 0
- O 0
selective O 0
beta O 0
- O 0
blocking O 0
properties O 0
of O 0
sotalol B-Chemical 0
. O 0

Effects O 0
of O 0
the O 0
antidepressant O 0
trazodone B-Chemical 0
, O 0
a O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
2A O 0
/ O 0
2C O 0
receptor O 0
antagonist O 0
, O 0
on O 0
dopamine B-Chemical 0
- O 0
dependent O 0
behaviors O 0
in O 0
rats O 0
. O 0

RATIONALE O 0
: O 0
5 B-Chemical 0
- I-Chemical 0
Hydroxytryptamine I-Chemical 0
, O 0
via O 0
stimulation O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
2C O 0
receptors O 0
, O 0
exerts O 0
a O 0
tonic O 0
inhibitory O 0
influence O 0
on O 0
dopaminergic O 0
neurotransmission O 0
, O 0
whereas O 0
activation O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
2A O 0
receptors O 0
enhances O 0
stimulated O 0
DAergic O 0
neurotransmission O 0
. O 0

The O 0
antidepressant O 0
trazodone B-Chemical 0
is O 0
a O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
2A O 0
/ O 0
2C O 0
receptor O 0
antagonist O 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
evaluate O 0
the O 0
effect O 0
of O 0
trazodone B-Chemical 0
treatment O 0
on O 0
behaviors O 0
dependent O 0
on O 0
the O 0
functional O 0
status O 0
of O 0
the O 0
nigrostriatal O 0
DAergic O 0
system O 0
. O 0

METHODS O 0
: O 0
The O 0
effect O 0
of O 0
pretreatment O 0
with O 0
trazodone B-Chemical 0
on O 0
dexamphetamine B-Chemical 0
- O 0
and O 0
apomorphine B-Chemical 0
- O 0
induced O 0
oral B-Disease 0
stereotypies I-Disease 0
, O 0
on O 0
catalepsy B-Disease 0
induced O 0
by O 0
haloperidol B-Chemical 0
and O 0
apomorphine B-Chemical 0
( O 0
0 O 0
. O 0
05 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
, O 0
on O 0
ergometrine B-Chemical 0
- O 0
induced O 0
wet O 0
dog O 0
shake O 0
( O 0
WDS O 0
) O 0
behavior O 0
and O 0
fluoxetine B-Chemical 0
- O 0
induced O 0
penile O 0
erections O 0
was O 0
studied O 0
in O 0
rats O 0
. O 0

We O 0
also O 0
investigated O 0
whether O 0
trazodone B-Chemical 0
induces O 0
catalepsy B-Disease 0
in O 0
rats O 0
. O 0

RESULTS O 0
: O 0
Trazodone B-Chemical 0
at O 0
2 O 0
. O 0
5 O 0
- O 0
20 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
did O 0
not O 0
induce O 0
catalepsy B-Disease 0
, O 0
and O 0
did O 0
not O 0
antagonize O 0
apomorphine B-Chemical 0
( O 0
1 O 0
. O 0
5 O 0
and O 0
3 O 0
mg O 0
/ O 0
kg O 0
) O 0
stereotypy O 0
and O 0
apomorphine B-Chemical 0
( O 0
0 O 0
. O 0
05 O 0
mg O 0
/ O 0
kg O 0
) O 0
- O 0
induced O 0
catalepsy B-Disease 0
. O 0

However O 0
, O 0
pretreatment O 0
with O 0
5 O 0
, O 0
10 O 0
and O 0
20 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
trazodone B-Chemical 0
enhanced O 0
dexamphetamine B-Chemical 0
stereotypy O 0
, O 0
and O 0
antagonized O 0
haloperidol B-Chemical 0
catalepsy B-Disease 0
, O 0
ergometrine B-Chemical 0
- O 0
induced O 0
WDS O 0
behavior O 0
and O 0
fluoxetine B-Chemical 0
- O 0
induced O 0
penile O 0
erections O 0
. O 0

Trazodone B-Chemical 0
at O 0
30 O 0
, O 0
40 O 0
and O 0
50 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
induced O 0
catalepsy B-Disease 0
and O 0
antagonized O 0
apomorphine B-Chemical 0
and O 0
dexamphetamine B-Chemical 0
stereotypies O 0
. O 0

CONCLUSIONS O 0
: O 0
Our O 0
results O 0
indicate O 0
that O 0
trazodone B-Chemical 0
at O 0
2 O 0
. O 0
5 O 0
- O 0
20 O 0
mg O 0
/ O 0
kg O 0
does O 0
not O 0
block O 0
pre O 0
- O 0
and O 0
postsynaptic O 0
striatal O 0
D2 O 0
DA O 0
receptors O 0
, O 0
while O 0
at O 0
30 O 0
, O 0
40 O 0
and O 0
50 O 0
mg O 0
/ O 0
kg O 0
it O 0
blocks O 0
postsynaptic O 0
striatal O 0
D2 O 0
DA O 0
receptors O 0
. O 0

Furthermore O 0
, O 0
at O 0
5 O 0
, O 0
10 O 0
and O 0
20 O 0
mg O 0
/ O 0
kg O 0
, O 0
trazodone B-Chemical 0
blocks O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
2A O 0
and O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
2C O 0
receptors O 0
. O 0

We O 0
suggest O 0
that O 0
trazodone B-Chemical 0
( O 0
5 O 0
, O 0
10 O 0
and O 0
20 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
by O 0
blocking O 0
the O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
2C O 0
receptors O 0
, O 0
releases O 0
the O 0
nigrostriatal O 0
DAergic O 0
neurons O 0
from O 0
tonic O 0
inhibition O 0
caused O 0
by O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
, O 0
and O 0
thereby O 0
potentiates O 0
dexamphetamine B-Chemical 0
stereotypy O 0
and O 0
antagonizes O 0
haloperidol B-Chemical 0
catalepsy B-Disease 0
. O 0

Swallowing B-Disease 0
abnormalities I-Disease 0
and O 0
dyskinesia B-Disease 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

Gastrointestinal B-Disease 0
abnormalities I-Disease 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
( O 0
PD B-Disease 0
) O 0
have O 0
been O 0
known O 0
for O 0
almost O 0
two O 0
centuries O 0
, O 0
but O 0
many O 0
aspects O 0
concerning O 0
their O 0
pathophysiology O 0
have O 0
not O 0
been O 0
completely O 0
clarified O 0
. O 0

The O 0
aim O 0
of O 0
this O 0
study O 0
was O 0
to O 0
characterize O 0
the O 0
oropharyngeal O 0
dynamics O 0
in O 0
PD B-Disease 0
patients O 0
with O 0
and O 0
without O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesia B-Disease 0
. O 0

Fifteen O 0
dyskinetic B-Disease 0
, O 0
12 O 0
nondyskinetic O 0
patients O 0
, O 0
and O 0
a O 0
control O 0
group O 0
were O 0
included O 0
. O 0

Patients O 0
were O 0
asked O 0
about O 0
dysphagia B-Disease 0
and O 0
evaluated O 0
with O 0
the O 0
Unified O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
Disease I-Disease 0
Rating O 0
Scale O 0
Parts O 0
II O 0
and O 0
III O 0
and O 0
the O 0
Hoehn O 0
and O 0
Yahr O 0
scale O 0
. O 0

Deglutition O 0
was O 0
assessed O 0
using O 0
modified O 0
barium B-Chemical 0
swallow O 0
with O 0
videofluoroscopy O 0
. O 0

Nondyskinetic O 0
patients O 0
, O 0
but O 0
not O 0
the O 0
dyskinetic B-Disease 0
ones O 0
, O 0
showed O 0
less O 0
oropharyngeal O 0
swallowing O 0
efficiency O 0
( O 0
OPSE O 0
) O 0
for O 0
liquid O 0
food O 0
than O 0
controls O 0
( O 0
Dunnett O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
02 O 0
) O 0
. O 0

Dyskinetic B-Disease 0
patients O 0
tended O 0
to O 0
have O 0
a O 0
greater O 0
OPSE O 0
than O 0
nondyskinetic O 0
( O 0
Dunnett O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
06 O 0
) O 0
. O 0

Patients O 0
who O 0
were O 0
using O 0
a O 0
higher O 0
dose O 0
of O 0
levodopa B-Chemical 0
had O 0
a O 0
greater O 0
OPSE O 0
and O 0
a O 0
trend O 0
toward O 0
a O 0
smaller O 0
oral O 0
transit O 0
time O 0
( O 0
Pearson O 0
' O 0
s O 0
correlation O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
01 O 0
and O 0
0 O 0
. O 0
08 O 0
, O 0
respectively O 0
) O 0
. O 0

Neither O 0
the O 0
report O 0
of O 0
dysphagia B-Disease 0
nor O 0
any O 0
of O 0
the O 0
PD B-Disease 0
severity O 0
parameters O 0
correlated O 0
to O 0
the O 0
videofluoroscopic O 0
variables O 0
. O 0

In O 0
the O 0
current O 0
study O 0
, O 0
dyskinetic B-Disease 0
patients O 0
performed O 0
better O 0
in O 0
swallowing O 0
function O 0
, O 0
which O 0
could O 0
be O 0
explained O 0
on O 0
the O 0
basis O 0
of O 0
a O 0
greater O 0
levodopa B-Chemical 0
dose O 0
. O 0

Our O 0
results O 0
suggest O 0
a O 0
role O 0
for O 0
levodopa B-Chemical 0
in O 0
the O 0
oral O 0
phase O 0
of O 0
deglutition O 0
and O 0
confirm O 0
that O 0
dysphagia B-Disease 0
is O 0
not O 0
a O 0
good O 0
predictor O 0
of O 0
deglutition O 0
alterations O 0
in O 0
PD B-Disease 0
. O 0

Inhibition O 0
of O 0
nuclear O 0
factor O 0
- O 0
kappaB O 0
activation O 0
attenuates O 0
tubulointerstitial B-Disease 0
nephritis I-Disease 0
induced O 0
by O 0
gentamicin B-Chemical 0
. O 0

BACKGROUND O 0
: O 0
Animals O 0
treated O 0
with O 0
gentamicin B-Chemical 0
can O 0
show O 0
residual O 0
areas O 0
of O 0
interstitial O 0
fibrosis B-Disease 0
in O 0
the O 0
renal O 0
cortex O 0
. O 0

This O 0
study O 0
investigated O 0
the O 0
expression O 0
of O 0
nuclear O 0
factor O 0
- O 0
kappaB O 0
( O 0
NF O 0
- O 0
kappaB O 0
) O 0
, O 0
mitogen O 0
- O 0
activated O 0
protein O 0
( O 0
MAP O 0
) O 0
kinases O 0
and O 0
macrophages O 0
in O 0
the O 0
renal O 0
cortex O 0
and O 0
structural O 0
and O 0
functional O 0
renal O 0
changes O 0
of O 0
rats O 0
treated O 0
with O 0
gentamicin B-Chemical 0
or O 0
gentamicin B-Chemical 0
+ O 0
pyrrolidine B-Chemical 0
dithiocarbamate I-Chemical 0
( O 0
PDTC B-Chemical 0
) O 0
, O 0
an O 0
NF O 0
- O 0
kappaB O 0
inhibitor O 0
. O 0

METHODS O 0
: O 0
38 O 0
female O 0
Wistar O 0
rats O 0
were O 0
injected O 0
with O 0
gentamicin B-Chemical 0
, O 0
40 O 0
mg O 0
/ O 0
kg O 0
, O 0
twice O 0
a O 0
day O 0
for O 0
9 O 0
days O 0
, O 0
38 O 0
with O 0
gentamicin B-Chemical 0
+ O 0
PDTC B-Chemical 0
, O 0
and O 0
28 O 0
with O 0
0 O 0
. O 0
15 O 0
M O 0
NaCl B-Chemical 0
solution O 0
. O 0

The O 0
animals O 0
were O 0
killed O 0
5 O 0
and O 0
30 O 0
days O 0
after O 0
these O 0
injections O 0
and O 0
the O 0
kidneys O 0
were O 0
removed O 0
for O 0
histological O 0
and O 0
immunohistochemical O 0
studies O 0
. O 0

The O 0
results O 0
of O 0
the O 0
immunohistochemical O 0
studies O 0
were O 0
scored O 0
according O 0
to O 0
the O 0
extent O 0
of O 0
staining O 0
. O 0

The O 0
fractional O 0
interstitial O 0
area O 0
was O 0
determined O 0
by O 0
morphometry O 0
. O 0

RESULTS O 0
: O 0
Gentamicin B-Chemical 0
- O 0
treated O 0
rats O 0
presented O 0
a O 0
transitory O 0
increase O 0
in O 0
plasma O 0
creatinine B-Chemical 0
levels O 0
. O 0

Increased O 0
ED O 0
- O 0
1 O 0
, O 0
MAP O 0
kinases O 0
and O 0
NF O 0
- O 0
kappaB O 0
staining O 0
were O 0
also O 0
observed O 0
in O 0
the O 0
renal O 0
cortex O 0
from O 0
all O 0
gentamicin B-Chemical 0
- O 0
treated O 0
rats O 0
compared O 0
to O 0
control O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

The O 0
animals O 0
killed O 0
on O 0
day O 0
30 O 0
also O 0
presented O 0
fibrosis B-Disease 0
in O 0
the O 0
renal O 0
cortex O 0
despite O 0
the O 0
recovery O 0
of O 0
renal O 0
function O 0
. O 0

Treatment O 0
with O 0
PDTC B-Chemical 0
reduced O 0
the O 0
functional O 0
and O 0
structural O 0
changes O 0
induced O 0
by O 0
gentamicin B-Chemical 0
. O 0

CONCLUSIONS O 0
: O 0
These O 0
data O 0
show O 0
that O 0
inhibition O 0
of O 0
NF O 0
- O 0
kappaB O 0
activation O 0
attenuates O 0
tubulointerstitial B-Disease 0
nephritis I-Disease 0
induced O 0
by O 0
gentamicin B-Chemical 0
. O 0

Glucose B-Chemical 0
metabolism O 0
in O 0
patients O 0
with O 0
schizophrenia B-Disease 0
treated O 0
with O 0
atypical O 0
antipsychotic O 0
agents O 0
: O 0
a O 0
frequently O 0
sampled O 0
intravenous O 0
glucose B-Chemical 0
tolerance O 0
test O 0
and O 0
minimal O 0
model O 0
analysis O 0
. O 0

BACKGROUND O 0
: O 0
While O 0
the O 0
incidence O 0
of O 0
new O 0
- O 0
onset O 0
diabetes B-Disease 0
mellitus I-Disease 0
may O 0
be O 0
increasing O 0
in O 0
patients O 0
with O 0
schizophrenia B-Disease 0
treated O 0
with O 0
certain O 0
atypical O 0
antipsychotic O 0
agents O 0
, O 0
it O 0
remains O 0
unclear O 0
whether O 0
atypical O 0
agents O 0
are O 0
directly O 0
affecting O 0
glucose B-Chemical 0
metabolism O 0
or O 0
simply O 0
increasing O 0
known O 0
risk O 0
factors O 0
for O 0
diabetes B-Disease 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
study O 0
the O 0
2 O 0
drugs O 0
most O 0
clearly O 0
implicated O 0
( O 0
clozapine B-Chemical 0
and O 0
olanzapine B-Chemical 0
) O 0
and O 0
risperidone B-Chemical 0
using O 0
a O 0
frequently O 0
sampled O 0
intravenous O 0
glucose B-Chemical 0
tolerance O 0
test O 0
. O 0

DESIGN O 0
: O 0
A O 0
cross O 0
- O 0
sectional O 0
design O 0
in O 0
stable O 0
, O 0
treated O 0
patients O 0
with O 0
schizophrenia B-Disease 0
evaluated O 0
using O 0
a O 0
frequently O 0
sampled O 0
intravenous O 0
glucose B-Chemical 0
tolerance O 0
test O 0
and O 0
the O 0
Bergman O 0
minimal O 0
model O 0
analysis O 0
. O 0

SETTING O 0
: O 0
Subjects O 0
were O 0
recruited O 0
from O 0
an O 0
urban O 0
community O 0
mental O 0
health O 0
clinic O 0
and O 0
were O 0
studied O 0
at O 0
a O 0
general O 0
clinical O 0
research O 0
center O 0
. O 0

Patients O 0
Fifty O 0
subjects O 0
signed O 0
informed O 0
consent O 0
and O 0
41 O 0
underwent O 0
the O 0
frequently O 0
sampled O 0
intravenous O 0
glucose B-Chemical 0
tolerance O 0
test O 0
. O 0

Thirty O 0
- O 0
six O 0
nonobese O 0
subjects O 0
with O 0
schizophrenia B-Disease 0
or O 0
schizoaffective B-Disease 0
disorder I-Disease 0
, O 0
matched O 0
by O 0
body O 0
mass O 0
index O 0
and O 0
treated O 0
with O 0
either O 0
clozapine B-Chemical 0
, O 0
olanzapine B-Chemical 0
, O 0
or O 0
risperidone B-Chemical 0
, O 0
were O 0
included O 0
in O 0
the O 0
analysis O 0
. O 0

MAIN O 0
OUTCOME O 0
MEASURES O 0
: O 0
Fasting O 0
plasma O 0
glucose B-Chemical 0
and O 0
fasting O 0
serum O 0
insulin O 0
levels O 0
, O 0
insulin B-Disease 0
sensitivity I-Disease 0
index O 0
, O 0
homeostasis O 0
model O 0
assessment O 0
of O 0
insulin B-Disease 0
resistance I-Disease 0
, O 0
and O 0
glucose B-Chemical 0
effectiveness O 0
. O 0

RESULTS O 0
: O 0
The O 0
mean O 0
+ O 0
/ O 0
- O 0
SD O 0
duration O 0
of O 0
treatment O 0
with O 0
the O 0
identified O 0
atypical O 0
antipsychotic O 0
agent O 0
was O 0
68 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
28 O 0
. O 0
9 O 0
months O 0
( O 0
clozapine B-Chemical 0
) O 0
, O 0
29 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
17 O 0
. O 0
5 O 0
months O 0
( O 0
olanzapine B-Chemical 0
) O 0
, O 0
and O 0
40 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
33 O 0
. O 0
7 O 0
( O 0
risperidone B-Chemical 0
) O 0
. O 0

Fasting O 0
serum O 0
insulin O 0
concentrations O 0
differed O 0
among O 0
groups O 0
( O 0
F O 0
( O 0
33 O 0
) O 0
= O 0
3 O 0
. O 0
35 O 0
; O 0
P O 0
= O 0
. O 0
047 O 0
) O 0
( O 0
clozapine B-Chemical 0
> O 0
olanzapine B-Chemical 0
> O 0
risperidone B-Chemical 0
) O 0
with O 0
significant O 0
differences O 0
between O 0
clozapine B-Chemical 0
and O 0
risperidone B-Chemical 0
( O 0
t O 0
( O 0
33 O 0
) O 0
= O 0
2 O 0
. O 0
32 O 0
; O 0
P O 0
= O 0
. O 0
03 O 0
) O 0
and O 0
olanzapine B-Chemical 0
and O 0
risperidone B-Chemical 0
( O 0
t O 0
( O 0
33 O 0
) O 0
= O 0
2 O 0
. O 0
15 O 0
; O 0
P O 0
= O 0
. O 0
04 O 0
) O 0
. O 0

There O 0
was O 0
a O 0
significant O 0
difference O 0
in O 0
insulin B-Disease 0
sensitivity I-Disease 0
index O 0
among O 0
groups O 0
( O 0
F O 0
( O 0
33 O 0
) O 0
= O 0
10 O 0
. O 0
66 O 0
; O 0
P O 0
< O 0
. O 0
001 O 0
) O 0
( O 0
clozapine B-Chemical 0
< O 0
olanzapine B-Chemical 0
< O 0
risperidone B-Chemical 0
) O 0
, O 0
with O 0
subjects O 0
who O 0
received O 0
clozapine B-Chemical 0
and O 0
olanzapine B-Chemical 0
exhibiting O 0
significant O 0
insulin B-Disease 0
resistance I-Disease 0
compared O 0
with O 0
subjects O 0
who O 0
were O 0
treated O 0
with O 0
risperidone B-Chemical 0
( O 0
clozapine B-Chemical 0
vs O 0
risperidone B-Chemical 0
, O 0
t O 0
( O 0
33 O 0
) O 0
= O 0
- O 0
4 O 0
. O 0
29 O 0
; O 0
P O 0
< O 0
. O 0
001 O 0
; O 0
olanzapine B-Chemical 0
vs O 0
risperidone B-Chemical 0
, O 0
t O 0
( O 0
33 O 0
) O 0
= O 0
- O 0
3 O 0
. O 0
62 O 0
; O 0
P O 0
= O 0
. O 0
001 O 0
[ O 0
P O 0
< O 0
. O 0
001 O 0
] O 0
) O 0
. O 0

The O 0
homeostasis O 0
model O 0
assessment O 0
of O 0
insulin B-Disease 0
resistance I-Disease 0
also O 0
differed O 0
significantly O 0
among O 0
groups O 0
( O 0
F O 0
( O 0
33 O 0
) O 0
= O 0
4 O 0
. O 0
92 O 0
; O 0
P O 0
= O 0
. O 0
01 O 0
) O 0
( O 0
clozapine B-Chemical 0
> O 0
olanzapine B-Chemical 0
> O 0
risperidone B-Chemical 0
) O 0
( O 0
clozapine B-Chemical 0
vs O 0
risperidone B-Chemical 0
, O 0
t O 0
( O 0
33 O 0
) O 0
= O 0
2 O 0
. O 0
94 O 0
; O 0
P O 0
= O 0
. O 0
006 O 0
; O 0
olanzapine B-Chemical 0
vs O 0
risperidone B-Chemical 0
, O 0
t O 0
( O 0
33 O 0
) O 0
= O 0
2 O 0
. O 0
42 O 0
; O 0
P O 0
= O 0
. O 0
02 O 0
) O 0
. O 0

There O 0
was O 0
a O 0
significant O 0
difference O 0
among O 0
groups O 0
in O 0
glucose B-Chemical 0
effectiveness O 0
( O 0
F O 0
( O 0
30 O 0
) O 0
= O 0
4 O 0
. O 0
18 O 0
; O 0
P O 0
= O 0
. O 0
02 O 0
) O 0
( O 0
clozapine B-Chemical 0
< O 0
olanzapine B-Chemical 0
< O 0
risperidone B-Chemical 0
) O 0
with O 0
significant O 0
differences O 0
between O 0
clozapine B-Chemical 0
and O 0
risperidone B-Chemical 0
( O 0
t O 0
( O 0
30 O 0
) O 0
= O 0
- O 0
2 O 0
. O 0
59 O 0
; O 0
P O 0
= O 0
. O 0
02 O 0
) O 0
and O 0
olanzapine B-Chemical 0
and O 0
risperidone B-Chemical 0
( O 0
t O 0
( O 0
30 O 0
) O 0
= O 0
- O 0
2 O 0
. O 0
34 O 0
, O 0
P O 0
= O 0
. O 0
03 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Both O 0
nonobese O 0
clozapine B-Chemical 0
- O 0
and O 0
olanzapine B-Chemical 0
- O 0
treated O 0
groups O 0
displayed O 0
significant O 0
insulin B-Disease 0
resistance I-Disease 0
and O 0
impairment O 0
of O 0
glucose B-Chemical 0
effectiveness O 0
compared O 0
with O 0
risperidone B-Chemical 0
- O 0
treated O 0
subjects O 0
. O 0

Patients O 0
taking O 0
clozapine B-Chemical 0
and O 0
olanzapine B-Chemical 0
must O 0
be O 0
examined O 0
for O 0
insulin B-Disease 0
resistance I-Disease 0
and O 0
its O 0
consequences O 0
. O 0

Thoracic B-Disease 0
hematomyelia I-Disease 0
secondary O 0
to O 0
coumadin B-Chemical 0
anticoagulant O 0
therapy O 0
: O 0
a O 0
case O 0
report O 0
. O 0

A O 0
case O 0
of O 0
thoracic B-Disease 0
hematomyelia I-Disease 0
secondary O 0
to O 0
anticoagulant O 0
therapy O 0
is O 0
presented O 0
. O 0

Clinical O 0
features O 0
, O 0
similar O 0
to O 0
2 O 0
other O 0
previously O 0
reported O 0
cases O 0
, O 0
are O 0
discussed O 0
. O 0

A O 0
high O 0
index O 0
of O 0
suspicion O 0
may O 0
lead O 0
to O 0
a O 0
quick O 0
diagnostic O 0
procedure O 0
and O 0
successful O 0
decompressive O 0
surgery O 0
. O 0

Mania B-Disease 0
associated O 0
with O 0
fluoxetine B-Chemical 0
treatment O 0
in O 0
adolescents O 0
. O 0

Fluoxetine B-Chemical 0
, O 0
a O 0
selective O 0
serotonin B-Chemical 0
reuptake O 0
inhibitor O 0
, O 0
is O 0
gaining O 0
increased O 0
acceptance O 0
in O 0
the O 0
treatment O 0
of O 0
adolescent O 0
depression B-Disease 0
. O 0

Generally O 0
safe O 0
and O 0
well O 0
tolerated O 0
by O 0
adults O 0
, O 0
fluoxetine B-Chemical 0
has O 0
been O 0
reported O 0
to O 0
induce O 0
mania B-Disease 0
. O 0

The O 0
cases O 0
of O 0
five O 0
depressed B-Disease 0
adolescents O 0
, O 0
14 O 0
- O 0
16 O 0
years O 0
of O 0
age O 0
, O 0
who O 0
developed O 0
mania B-Disease 0
during O 0
pharmacotherapy O 0
with O 0
fluoxetine B-Chemical 0
, O 0
are O 0
reported O 0
here O 0
. O 0

Apparent O 0
risk O 0
factors O 0
for O 0
the O 0
development O 0
of O 0
mania B-Disease 0
or O 0
hypomania B-Disease 0
during O 0
fluoxetine B-Chemical 0
pharmacotherapy O 0
in O 0
this O 0
population O 0
were O 0
the O 0
combination O 0
of O 0
attention B-Disease 0
- I-Disease 0
deficit I-Disease 0
hyperactivity I-Disease 0
disorder I-Disease 0
and O 0
affective O 0
instability O 0
; O 0
major O 0
depression B-Disease 0
with O 0
psychotic B-Disease 0
features O 0
; O 0
a O 0
family O 0
history O 0
of O 0
affective B-Disease 0
disorder I-Disease 0
, O 0
especially O 0
bipolar B-Disease 0
disorder I-Disease 0
; O 0
and O 0
a O 0
diagnosis O 0
of O 0
bipolar B-Disease 0
disorder I-Disease 0
. O 0

Further O 0
study O 0
is O 0
needed O 0
to O 0
determine O 0
the O 0
optimal O 0
dosage O 0
and O 0
to O 0
identify O 0
risk O 0
factors O 0
that O 0
increase O 0
individual O 0
vulnerability O 0
to O 0
fluoxetine B-Chemical 0
induced O 0
mania B-Disease 0
in O 0
adolescents O 0
. O 0

Acute B-Disease 0
renal I-Disease 0
insufficiency I-Disease 0
after O 0
high O 0
- O 0
dose O 0
melphalan B-Chemical 0
in O 0
patients O 0
with O 0
primary B-Disease 0
systemic I-Disease 0
amyloidosis I-Disease 0
during O 0
stem O 0
cell O 0
transplantation O 0
. O 0

BACKGROUND O 0
: O 0
Patients O 0
with O 0
primary B-Disease 0
systemic I-Disease 0
amyloidosis I-Disease 0
( O 0
AL B-Disease 0
) O 0
have O 0
a O 0
poor O 0
prognosis O 0
. O 0

Median O 0
survival O 0
time O 0
from O 0
standard O 0
treatments O 0
is O 0
only O 0
17 O 0
months O 0
. O 0

High O 0
- O 0
dose O 0
intravenous O 0
melphalan B-Chemical 0
followed O 0
by O 0
peripheral O 0
blood O 0
stem O 0
cell O 0
transplant O 0
( O 0
PBSCT O 0
) O 0
appears O 0
to O 0
be O 0
the O 0
most O 0
promising O 0
therapy O 0
, O 0
but O 0
treatment O 0
mortality O 0
can O 0
be O 0
high O 0
. O 0

The O 0
authors O 0
have O 0
noted O 0
the O 0
development O 0
of O 0
acute B-Disease 0
renal I-Disease 0
insufficiency I-Disease 0
immediately O 0
after O 0
melphalan B-Chemical 0
conditioning O 0
. O 0

This O 0
study O 0
was O 0
undertaken O 0
to O 0
further O 0
examine O 0
its O 0
risk O 0
factors O 0
and O 0
impact O 0
on O 0
posttransplant O 0
mortality O 0
. O 0

METHODS O 0
: O 0
Consecutive O 0
AL B-Disease 0
patients O 0
who O 0
underwent O 0
PBSCT O 0
were O 0
studied O 0
retrospectively O 0
. O 0

Acute B-Disease 0
renal I-Disease 0
insufficiency I-Disease 0
( O 0
ARI B-Disease 0
) O 0
after O 0
high O 0
- O 0
dose O 0
melphalan B-Chemical 0
was O 0
defined O 0
by O 0
a O 0
minimum O 0
increase O 0
of O 0
0 O 0
. O 0
5 O 0
mg O 0
/ O 0
dL O 0
( O 0
44 O 0
micromol O 0
/ O 0
L O 0
) O 0
in O 0
the O 0
serum O 0
creatinine B-Chemical 0
level O 0
that O 0
is O 0
greater O 0
than O 0
50 O 0
% O 0
of O 0
baseline O 0
immediately O 0
after O 0
conditioning O 0
. O 0

Urine O 0
sediment O 0
score O 0
was O 0
the O 0
sum O 0
of O 0
the O 0
individual O 0
types O 0
of O 0
sediment O 0
identified O 0
on O 0
urine O 0
microscopy O 0
. O 0

RESULTS O 0
: O 0
Of O 0
the O 0
80 O 0
patients O 0
studied O 0
, O 0
ARI B-Disease 0
developed O 0
in O 0
18 O 0
. O 0
8 O 0
% O 0
of O 0
the O 0
patients O 0
after O 0
high O 0
- O 0
dose O 0
melphalan B-Chemical 0
. O 0

Univariate O 0
analysis O 0
identified O 0
age O 0
, O 0
hypoalbuminemia B-Disease 0
, O 0
heavy O 0
proteinuria B-Disease 0
, O 0
diuretic O 0
use O 0
, O 0
and O 0
urine O 0
sediment O 0
score O 0
( O 0
> O 0
3 O 0
) O 0
as O 0
risk O 0
factors O 0
. O 0

Age O 0
and O 0
urine O 0
sediment O 0
score O 0
remained O 0
independently O 0
significant O 0
risk O 0
factors O 0
in O 0
the O 0
multivariate O 0
analysis O 0
. O 0

Patients O 0
who O 0
had O 0
ARI B-Disease 0
after O 0
high O 0
- O 0
dose O 0
melphalan B-Chemical 0
underwent O 0
dialysis O 0
more O 0
often O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
007 O 0
) O 0
, O 0
and O 0
had O 0
a O 0
worse O 0
1 O 0
- O 0
year O 0
survival O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
03 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
timing O 0
of O 0
renal B-Disease 0
injury I-Disease 0
strongly O 0
suggests O 0
melphalan B-Chemical 0
as O 0
the O 0
causative O 0
agent O 0
. O 0

Ongoing O 0
tubular B-Disease 0
injury I-Disease 0
may O 0
be O 0
a O 0
prerequisite O 0
for O 0
renal B-Disease 0
injury I-Disease 0
by O 0
melphalan B-Chemical 0
as O 0
evidenced O 0
by O 0
the O 0
active O 0
urinary O 0
sediment O 0
. O 0

Development O 0
of O 0
ARI B-Disease 0
adversely O 0
affected O 0
the O 0
outcome O 0
after O 0
PBSCT O 0
. O 0

Effective O 0
preventive O 0
measures O 0
may O 0
help O 0
decrease O 0
the O 0
treatment O 0
mortality O 0
of O 0
PBSCT O 0
in O 0
AL B-Disease 0
patients O 0
. O 0

Focal O 0
cerebral B-Disease 0
ischemia I-Disease 0
in O 0
rats O 0
: O 0
effect O 0
of O 0
phenylephrine B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
during O 0
reperfusion O 0
. O 0

After O 0
180 O 0
min O 0
of O 0
temporary O 0
middle B-Disease 0
cerebral I-Disease 0
artery I-Disease 0
occlusion I-Disease 0
in O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
, O 0
the O 0
effect O 0
of O 0
phenylephrine B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
on O 0
ischemic B-Disease 0
brain I-Disease 0
injury I-Disease 0
and O 0
blood O 0
- O 0
brain O 0
barrier O 0
permeability O 0
was O 0
determined O 0
. O 0

Blood O 0
pressure O 0
was O 0
manipulated O 0
by O 0
one O 0
of O 0
the O 0
following O 0
schedules O 0
during O 0
120 O 0
min O 0
of O 0
reperfusion O 0
: O 0
Control O 0
, O 0
normotensive O 0
reperfusion O 0
; O 0
90 O 0
/ O 0
hypertension B-Disease 0
( O 0
90 O 0
/ O 0
HTN B-Disease 0
) O 0
, O 0
blood O 0
pressure O 0
was O 0
increased O 0
by O 0
35 O 0
mm O 0
Hg O 0
during O 0
the O 0
initial O 0
90 O 0
min O 0
of O 0
reperfusion O 0
only O 0
; O 0
15 O 0
/ O 0
hypertension B-Disease 0
( O 0
15 O 0
/ O 0
HTN B-Disease 0
) O 0
, O 0
normotensive O 0
reperfusion O 0
for O 0
30 O 0
min O 0
followed O 0
by O 0
15 O 0
min O 0
of O 0
hypertension B-Disease 0
and O 0
75 O 0
min O 0
of O 0
normotension O 0
. O 0

Part O 0
A O 0
, O 0
for O 0
eight O 0
rats O 0
in O 0
each O 0
group O 0
brain B-Disease 0
injury I-Disease 0
was O 0
evaluated O 0
by O 0
staining O 0
tissue O 0
using O 0
2 B-Chemical 0
, I-Chemical 0
3 I-Chemical 0
, I-Chemical 0
5 I-Chemical 0
- I-Chemical 0
triphenyltetrazolium I-Chemical 0
chloride I-Chemical 0
and O 0
edema B-Disease 0
was O 0
evaluated O 0
by O 0
microgravimetry O 0
. O 0

Part O 0
B O 0
, O 0
for O 0
eight O 0
different O 0
rats O 0
in O 0
each O 0
group O 0
blood O 0
- O 0
brain O 0
barrier O 0
permeability O 0
was O 0
evaluated O 0
by O 0
measuring O 0
the O 0
amount O 0
and O 0
extent O 0
of O 0
extravasation O 0
of O 0
Evans O 0
Blue O 0
dye O 0
. O 0

Brain B-Disease 0
injury I-Disease 0
( O 0
percentage O 0
of O 0
the O 0
ischemic B-Disease 0
hemisphere I-Disease 0
) O 0
was O 0
less O 0
in O 0
the O 0
15 O 0
/ O 0
HTN B-Disease 0
group O 0
( O 0
16 O 0
+ O 0
/ O 0
- O 0
6 O 0
, O 0
mean O 0
+ O 0
/ O 0
- O 0
SD O 0
) O 0
versus O 0
the O 0
90 O 0
/ O 0
HTN B-Disease 0
group O 0
( O 0
30 O 0
+ O 0
/ O 0
- O 0
6 O 0
) O 0
, O 0
which O 0
was O 0
in O 0
turn O 0
less O 0
than O 0
the O 0
control O 0
group O 0
( O 0
42 O 0
+ O 0
/ O 0
- O 0
5 O 0
) O 0
. O 0

Specific O 0
gravity O 0
was O 0
greater O 0
in O 0
the O 0
15 O 0
/ O 0
HTN B-Disease 0
group O 0
( O 0
1 O 0
. O 0
043 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
002 O 0
) O 0
versus O 0
the O 0
90 O 0
/ O 0
HTN B-Disease 0
( O 0
1 O 0
. O 0
036 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
003 O 0
) O 0
and O 0
control O 0
( O 0
1 O 0
. O 0
037 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
003 O 0
) O 0
groups O 0
. O 0

Evans B-Chemical 0
Blue I-Chemical 0
( O 0
mug O 0
g O 0
- O 0
1 O 0
of O 0
brain O 0
tissue O 0
) O 0
was O 0
greater O 0
in O 0
the O 0
90 O 0
/ O 0
HTN B-Disease 0
group O 0
( O 0
24 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
6 O 0
. O 0
0 O 0
) O 0
versus O 0
the O 0
control O 0
group O 0
( O 0
12 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
1 O 0
) O 0
, O 0
which O 0
was O 0
in O 0
turn O 0
greater O 0
than O 0
the O 0
15 O 0
/ O 0
HTN B-Disease 0
group O 0
( O 0
7 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
2 O 0
) O 0
. O 0

This O 0
study O 0
supports O 0
a O 0
hypothesis O 0
that O 0
during O 0
reperfusion O 0
, O 0
a O 0
short O 0
interval O 0
of O 0
hypertension B-Disease 0
decreases O 0
brain B-Disease 0
injury I-Disease 0
and O 0
edema B-Disease 0
; O 0
and O 0
that O 0
sustained O 0
hypertension B-Disease 0
increases O 0
the O 0
risk O 0
of O 0
vasogenic B-Disease 0
edema I-Disease 0
. O 0

People O 0
aged O 0
over O 0
75 O 0
in O 0
atrial B-Disease 0
fibrillation I-Disease 0
on O 0
warfarin B-Chemical 0
: O 0
the O 0
rate O 0
of O 0
major O 0
hemorrhage B-Disease 0
and O 0
stroke B-Disease 0
in O 0
more O 0
than O 0
500 O 0
patient O 0
- O 0
years O 0
of O 0
follow O 0
- O 0
up O 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
determine O 0
the O 0
incidence O 0
of O 0
major O 0
hemorrhage B-Disease 0
and O 0
stroke B-Disease 0
in O 0
people O 0
aged O 0
76 O 0
and O 0
older O 0
with O 0
atrial B-Disease 0
fibrillation I-Disease 0
on O 0
adjusted O 0
- O 0
dose O 0
warfarin B-Chemical 0
who O 0
had O 0
been O 0
recently O 0
been O 0
admitted O 0
to O 0
hospital O 0
. O 0

DESIGN O 0
: O 0
A O 0
retrospective O 0
observational O 0
cohort O 0
study O 0
. O 0

SETTING O 0
: O 0
A O 0
major O 0
healthcare O 0
network O 0
involving O 0
four O 0
tertiary O 0
hospitals O 0
. O 0

PARTICIPANTS O 0
: O 0
Two O 0
hundred O 0
thirty O 0
- O 0
five O 0
patients O 0
aged O 0
76 O 0
and O 0
older O 0
admitted O 0
to O 0
a O 0
major O 0
healthcare O 0
network O 0
between O 0
July O 0
1 O 0
, O 0
2001 O 0
, O 0
and O 0
June O 0
30 O 0
, O 0
2002 O 0
, O 0
with O 0
atrial B-Disease 0
fibrillation I-Disease 0
on O 0
warfarin B-Chemical 0
were O 0
enrolled O 0
. O 0

MEASUREMENTS O 0
: O 0
Information O 0
regarding O 0
major O 0
bleeding B-Disease 0
episodes O 0
, O 0
strokes B-Disease 0
, O 0
and O 0
warfarin B-Chemical 0
use O 0
was O 0
obtained O 0
from O 0
patients O 0
, O 0
relatives O 0
, O 0
primary O 0
physicians O 0
, O 0
and O 0
medical O 0
records O 0
. O 0

RESULTS O 0
: O 0
Two O 0
hundred O 0
twenty O 0
- O 0
eight O 0
patients O 0
( O 0
42 O 0
% O 0
men O 0
) O 0
with O 0
a O 0
mean O 0
age O 0
of O 0
81 O 0
. O 0
1 O 0
( O 0
range O 0
76 O 0
- O 0
94 O 0
) O 0
were O 0
included O 0
in O 0
the O 0
analysis O 0
. O 0

Total O 0
follow O 0
- O 0
up O 0
on O 0
warfarin B-Chemical 0
was O 0
530 O 0
years O 0
( O 0
mean O 0
28 O 0
months O 0
) O 0
. O 0

There O 0
were O 0
53 O 0
major O 0
hemorrhages B-Disease 0
, O 0
for O 0
an O 0
annual O 0
rate O 0
of O 0
10 O 0
. O 0
0 O 0
% O 0
, O 0
including O 0
24 O 0
( O 0
45 O 0
. O 0
3 O 0
% O 0
) O 0
life O 0
- O 0
threatening O 0
and O 0
five O 0
( O 0
9 O 0
. O 0
4 O 0
% O 0
) O 0
fatal O 0
bleeds O 0
. O 0

The O 0
annual O 0
stroke B-Disease 0
rate O 0
after O 0
initiation O 0
of O 0
warfarin B-Chemical 0
was O 0
2 O 0
. O 0
6 O 0
% O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
rate O 0
of O 0
major O 0
hemorrhage B-Disease 0
was O 0
high O 0
in O 0
this O 0
old O 0
, O 0
frail O 0
group O 0
, O 0
but O 0
excluding O 0
fatalities O 0
, O 0
resulted O 0
in O 0
no O 0
long O 0
- O 0
term O 0
sequelae O 0
, O 0
and O 0
the O 0
stroke B-Disease 0
rate O 0
on O 0
warfarin B-Chemical 0
was O 0
low O 0
, O 0
demonstrating O 0
how O 0
effective O 0
warfarin B-Chemical 0
treatment O 0
is O 0
. O 0

Safety O 0
of O 0
celecoxib B-Chemical 0
in O 0
patients O 0
with O 0
adverse O 0
skin B-Disease 0
reactions I-Disease 0
to O 0
acetaminophen B-Chemical 0
( O 0
paracetamol B-Chemical 0
) O 0
and O 0
nimesulide B-Chemical 0
associated O 0
or O 0
not O 0
with O 0
common O 0
non O 0
- O 0
steroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
. O 0

BACKGROUND O 0
: O 0
Acetaminophen B-Chemical 0
( O 0
paracetamol B-Chemical 0
- O 0
- O 0
P B-Chemical 0
) O 0
and O 0
Nimesulide B-Chemical 0
( O 0
N B-Chemical 0
) O 0
are O 0
widely O 0
used O 0
analgesic O 0
- O 0
antipyretic O 0
/ O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
. O 0

The O 0
rate O 0
of O 0
adverse O 0
hypersensitivity B-Disease 0
reactions O 0
to O 0
these O 0
agents O 0
is O 0
generally O 0
low O 0
. O 0

On O 0
the O 0
contrary O 0
non O 0
- O 0
steroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
( O 0
NSAIDs O 0
) O 0
are O 0
commonly O 0
involved O 0
in O 0
such O 0
reactions O 0
. O 0

Celecoxib B-Chemical 0
( O 0
CE B-Chemical 0
) O 0
is O 0
a O 0
novel O 0
drug O 0
, O 0
with O 0
high O 0
selectivity O 0
and O 0
affinity O 0
for O 0
COX O 0
- O 0
2 O 0
enzyme O 0
. O 0

OBJECTIVE O 0
: O 0
We O 0
evaluated O 0
the O 0
tolerability O 0
of O 0
CE B-Chemical 0
in O 0
a O 0
group O 0
of O 0
patients O 0
with O 0
documented O 0
history O 0
of O 0
adverse O 0
cutaneous B-Disease 0
reactions I-Disease 0
to O 0
P B-Chemical 0
and O 0
N B-Chemical 0
associated O 0
or O 0
not O 0
to O 0
classic O 0
NSAIDs O 0
. O 0

METHODS O 0
: O 0
We O 0
studied O 0
9 O 0
patients O 0
with O 0
hypersensitivity B-Disease 0
to O 0
P B-Chemical 0
and O 0
N B-Chemical 0
with O 0
or O 0
without O 0
associated O 0
reactions O 0
to O 0
classic O 0
NSAIDs O 0
. O 0

The O 0
diagnosis O 0
of O 0
P B-Chemical 0
and O 0
N B-Chemical 0
- O 0
induced O 0
skin B-Disease 0
reactions I-Disease 0
was O 0
based O 0
in O 0
vivo O 0
challenge O 0
. O 0

The O 0
placebo O 0
was O 0
blindly O 0
administered O 0
at O 0
the O 0
beginning O 0
of O 0
each O 0
challenge O 0
. O 0

After O 0
three O 0
days O 0
, O 0
a O 0
cumulative O 0
dosage O 0
of O 0
200 O 0
mg O 0
of O 0
CE B-Chemical 0
in O 0
refracted O 0
doses O 0
were O 0
given O 0
. O 0

After O 0
2 O 0
- O 0
3 O 0
days O 0
, O 0
a O 0
single O 0
dose O 0
of O 0
200 O 0
mg O 0
was O 0
administered O 0
. O 0

All O 0
patients O 0
were O 0
observed O 0
for O 0
6 O 0
hours O 0
after O 0
each O 0
challenge O 0
, O 0
and O 0
controlled O 0
again O 0
after O 0
24 O 0
hours O 0
to O 0
exclude O 0
delayed O 0
reactions O 0
. O 0

The O 0
challenge O 0
was O 0
considered O 0
positive O 0
if O 0
one O 0
or O 0
more O 0
of O 0
the O 0
following O 0
appeared O 0
: O 0
erythema B-Disease 0
, O 0
rush O 0
or O 0
urticaria B-Disease 0
- O 0
angioedema B-Disease 0
. O 0

RESULTS O 0
: O 0
No O 0
reaction O 0
was O 0
observed O 0
with O 0
placebo O 0
and O 0
eight O 0
patients O 0
( O 0
88 O 0
. O 0
8 O 0
% O 0
) O 0
tolerated O 0
CE B-Chemical 0
. O 0

Only O 0
one O 0
patient O 0
developed O 0
a O 0
moderate O 0
angioedema B-Disease 0
of O 0
the O 0
lips O 0
. O 0

CONCLUSION O 0
: O 0
Only O 0
one O 0
hypersensitivity B-Disease 0
reaction O 0
to O 0
CE B-Chemical 0
was O 0
documented O 0
among O 0
9 O 0
P B-Chemical 0
and O 0
N B-Chemical 0
- O 0
highly O 0
NSAIDs O 0
intolerant O 0
patients O 0
. O 0

Thus O 0
, O 0
we O 0
conclude O 0
that O 0
CE B-Chemical 0
is O 0
a O 0
reasonably O 0
safe O 0
alternative O 0
to O 0
be O 0
used O 0
in O 0
subjects O 0
who O 0
do O 0
not O 0
tolerate O 0
P B-Chemical 0
and O 0
N B-Chemical 0
. O 0

Case O 0
- O 0
control O 0
study O 0
of O 0
regular O 0
analgesic O 0
and O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
use O 0
and O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
renal I-Disease 0
disease I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Studies O 0
on O 0
the O 0
association O 0
between O 0
the O 0
long O 0
- O 0
term O 0
use O 0
of O 0
aspirin B-Chemical 0
and O 0
other O 0
analgesic O 0
and O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
( O 0
NSAIDs O 0
) O 0
and O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
renal I-Disease 0
disease I-Disease 0
( O 0
ESRD B-Disease 0
) O 0
have O 0
given O 0
conflicting O 0
results O 0
. O 0

In O 0
order O 0
to O 0
examine O 0
this O 0
association O 0
, O 0
a O 0
case O 0
- O 0
control O 0
study O 0
with O 0
incident O 0
cases O 0
of O 0
ESRD B-Disease 0
was O 0
carried O 0
out O 0
. O 0

METHODS O 0
: O 0
The O 0
cases O 0
were O 0
all O 0
patients O 0
entering O 0
the O 0
local O 0
dialysis O 0
program O 0
because O 0
of O 0
ESRD B-Disease 0
in O 0
the O 0
study O 0
area O 0
between O 0
June O 0
1 O 0
, O 0
1995 O 0
and O 0
November O 0
30 O 0
, O 0
1997 O 0
. O 0

They O 0
were O 0
classified O 0
according O 0
to O 0
the O 0
underlying O 0
disease O 0
, O 0
which O 0
had O 0
presumably O 0
led O 0
them O 0
to O 0
ESRD B-Disease 0
. O 0

Controls O 0
were O 0
patients O 0
admitted O 0
to O 0
the O 0
same O 0
hospitals O 0
from O 0
where O 0
the O 0
cases O 0
arose O 0
, O 0
also O 0
matched O 0
by O 0
age O 0
and O 0
sex O 0
. O 0

Odds O 0
ratios O 0
were O 0
calculated O 0
using O 0
a O 0
conditional O 0
logistic O 0
model O 0
, O 0
including O 0
potential O 0
confounding O 0
factors O 0
, O 0
both O 0
for O 0
the O 0
whole O 0
study O 0
population O 0
and O 0
for O 0
the O 0
various O 0
underlying O 0
diseases O 0
. O 0

RESULTS O 0
: O 0
Five O 0
hundred O 0
and O 0
eighty O 0
- O 0
three O 0
cases O 0
and O 0
1190 O 0
controls O 0
were O 0
included O 0
in O 0
the O 0
analysis O 0
. O 0

Long O 0
- O 0
term O 0
use O 0
of O 0
any O 0
analgesic O 0
was O 0
associated O 0
with O 0
an O 0
overall O 0
odds O 0
ratio O 0
of O 0
1 O 0
. O 0
22 O 0
( O 0
95 O 0
% O 0
CI O 0
, O 0
0 O 0
. O 0
89 O 0
- O 0
1 O 0
. O 0
66 O 0
) O 0
. O 0

For O 0
specific O 0
groups O 0
of O 0
drugs O 0
, O 0
the O 0
risks O 0
were O 0
1 O 0
. O 0
56 O 0
( O 0
1 O 0
. O 0
05 O 0
- O 0
2 O 0
. O 0
30 O 0
) O 0
for O 0
aspirin B-Chemical 0
, O 0
1 O 0
. O 0
03 O 0
( O 0
0 O 0
. O 0
60 O 0
- O 0
1 O 0
. O 0
76 O 0
) O 0
for O 0
pyrazolones B-Chemical 0
, O 0
0 O 0
. O 0
80 O 0
( O 0
0 O 0
. O 0
39 O 0
- O 0
1 O 0
. O 0
63 O 0
) O 0
for O 0
paracetamol B-Chemical 0
, O 0
and O 0
0 O 0
. O 0
94 O 0
( O 0
0 O 0
. O 0
57 O 0
- O 0
1 O 0
. O 0
56 O 0
) O 0
for O 0
nonaspirin O 0
NSAIDs O 0
. O 0

The O 0
risk O 0
of O 0
ESRD B-Disease 0
associated O 0
with O 0
aspirin B-Chemical 0
was O 0
related O 0
to O 0
the O 0
cumulated O 0
dose O 0
and O 0
duration O 0
of O 0
use O 0
, O 0
and O 0
it O 0
was O 0
particularly O 0
high O 0
among O 0
the O 0
subset O 0
of O 0
patients O 0
with O 0
vascular O 0
nephropathy B-Disease 0
as O 0
underlying O 0
disease O 0
[ O 0
2 O 0
. O 0
35 O 0
( O 0
1 O 0
. O 0
17 O 0
- O 0
4 O 0
. O 0
72 O 0
) O 0
] O 0
. O 0

CONCLUSION O 0
: O 0
Our O 0
data O 0
indicate O 0
that O 0
long O 0
- O 0
term O 0
use O 0
of O 0
nonaspirin O 0
analgesic O 0
drugs O 0
and O 0
NSAIDs O 0
is O 0
not O 0
associated O 0
with O 0
an O 0
increased O 0
risk O 0
of O 0
ESRD B-Disease 0
. O 0

However O 0
, O 0
the O 0
chronic O 0
use O 0
of O 0
aspirin B-Chemical 0
may O 0
increase O 0
the O 0
risk O 0
of O 0
ESRD B-Disease 0
. O 0

Two O 0
cases O 0
of O 0
amisulpride B-Chemical 0
overdose B-Disease 0
: O 0
a O 0
cause O 0
for O 0
prolonged B-Disease 0
QT I-Disease 0
syndrome I-Disease 0
. O 0

Two O 0
cases O 0
of O 0
deliberate O 0
self O 0
- O 0
poisoning B-Disease 0
with O 0
5 O 0
g O 0
and O 0
3 O 0
. O 0
6 O 0
g O 0
of O 0
amisulpride B-Chemical 0
, O 0
respectively O 0
, O 0
are O 0
reported O 0
. O 0

In O 0
both O 0
cases O 0
, O 0
QT B-Disease 0
prolongation I-Disease 0
and O 0
hypocalcaemia B-Disease 0
were O 0
noted O 0
. O 0

The O 0
QT B-Disease 0
prolongation I-Disease 0
appeared O 0
to O 0
respond O 0
to O 0
administration O 0
of O 0
i O 0
. O 0
v O 0
. O 0
calcium B-Chemical 0
gluconate I-Chemical 0
. O 0

Growth O 0
- O 0
associated O 0
protein O 0
43 O 0
expression O 0
in O 0
hippocampal O 0
molecular O 0
layer O 0
of O 0
chronic O 0
epileptic B-Disease 0
rats O 0
treated O 0
with O 0
cycloheximide B-Chemical 0
. O 0

PURPOSE O 0
: O 0
GAP43 O 0
has O 0
been O 0
thought O 0
to O 0
be O 0
linked O 0
with O 0
mossy O 0
fiber O 0
sprouting O 0
( O 0
MFS O 0
) O 0
in O 0
various O 0
experimental O 0
models O 0
of O 0
epilepsy B-Disease 0
. O 0

To O 0
investigate O 0
how O 0
GAP43 O 0
expression O 0
( O 0
GAP43 O 0
- O 0
ir O 0
) O 0
correlates O 0
with O 0
MFS O 0
, O 0
we O 0
assessed O 0
the O 0
intensity O 0
( O 0
densitometry O 0
) O 0
and O 0
extension O 0
( O 0
width O 0
) O 0
of O 0
GAP43 O 0
- O 0
ir O 0
in O 0
the O 0
inner O 0
molecular O 0
layer O 0
of O 0
the O 0
dentate O 0
gyrus O 0
( O 0
IML O 0
) O 0
of O 0
rats O 0
subject O 0
to O 0
status B-Disease 0
epilepticus I-Disease 0
induced O 0
by O 0
pilocarpine B-Chemical 0
( O 0
Pilo B-Chemical 0
) O 0
, O 0
previously O 0
injected O 0
or O 0
not O 0
with O 0
cycloheximide B-Chemical 0
( O 0
CHX B-Chemical 0
) O 0
, O 0
which O 0
has O 0
been O 0
shown O 0
to O 0
inhibit O 0
MFS O 0
. O 0

METHODS O 0
: O 0
CHX B-Chemical 0
was O 0
injected O 0
before O 0
the O 0
Pilo B-Chemical 0
injection O 0
in O 0
adult O 0
Wistar O 0
rats O 0
. O 0

The O 0
Pilo B-Chemical 0
group O 0
was O 0
injected O 0
with O 0
the O 0
same O 0
drugs O 0
, O 0
except O 0
for O 0
CHX B-Chemical 0
. O 0

Animals O 0
were O 0
killed O 0
between O 0
30 O 0
and O 0
60 O 0
days O 0
later O 0
, O 0
and O 0
brain O 0
sections O 0
were O 0
processed O 0
for O 0
GAP43 O 0
immunohistochemistry O 0
. O 0

RESULTS O 0
: O 0
Densitometry O 0
showed O 0
no O 0
significant O 0
difference O 0
regarding O 0
GAP43 O 0
- O 0
ir O 0
in O 0
the O 0
IML O 0
between O 0
Pilo B-Chemical 0
, O 0
CHX B-Chemical 0
+ O 0
Pilo B-Chemical 0
, O 0
and O 0
control O 0
groups O 0
. O 0

However O 0
, O 0
the O 0
results O 0
of O 0
the O 0
width O 0
of O 0
the O 0
GAP43 O 0
- O 0
ir O 0
band O 0
in O 0
the O 0
IML O 0
showed O 0
that O 0
CHX B-Chemical 0
+ O 0
Pilo B-Chemical 0
and O 0
control O 0
animals O 0
had O 0
a O 0
significantly O 0
larger O 0
band O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
03 O 0
) O 0
as O 0
compared O 0
with O 0
that O 0
in O 0
the O 0
Pilo B-Chemical 0
group O 0
. O 0

CONCLUSIONS O 0
: O 0
Our O 0
current O 0
finding O 0
that O 0
animals O 0
in O 0
the O 0
CHX B-Chemical 0
+ O 0
Pilo B-Chemical 0
group O 0
have O 0
a O 0
GAP43 O 0
- O 0
ir O 0
band O 0
in O 0
the O 0
IML O 0
, O 0
similar O 0
to O 0
that O 0
of O 0
controls O 0
, O 0
reinforces O 0
prior O 0
data O 0
on O 0
the O 0
blockade O 0
of O 0
MFS O 0
in O 0
these O 0
animals O 0
. O 0

The O 0
change O 0
in O 0
GAP43 O 0
- O 0
ir O 0
present O 0
in O 0
Pilo B-Chemical 0
- O 0
treated O 0
animals O 0
was O 0
a O 0
thinning O 0
of O 0
the O 0
band O 0
to O 0
a O 0
very O 0
narrow O 0
layer O 0
just O 0
above O 0
the O 0
granule O 0
cell O 0
layer O 0
that O 0
is O 0
likely O 0
to O 0
be O 0
associated O 0
with O 0
the O 0
loss O 0
of O 0
hilar O 0
cell O 0
projections O 0
that O 0
express O 0
GAP O 0
- O 0
43 O 0
. O 0

Nicotine B-Chemical 0
antagonizes O 0
caffeine B-Chemical 0
- O 0
but O 0
not O 0
pentylenetetrazole B-Chemical 0
- O 0
induced O 0
anxiogenic O 0
effect O 0
in O 0
mice O 0
. O 0

RATIONALE O 0
: O 0
Nicotine B-Chemical 0
and O 0
caffeine B-Chemical 0
are O 0
widely O 0
consumed O 0
licit O 0
psychoactive O 0
drugs O 0
worldwide O 0
. O 0

Epidemiological O 0
studies O 0
showed O 0
that O 0
they O 0
were O 0
generally O 0
used O 0
concurrently O 0
. O 0

Although O 0
some O 0
studies O 0
in O 0
experimental O 0
animals O 0
indicate O 0
clear O 0
pharmacological O 0
interactions O 0
between O 0
them O 0
, O 0
no O 0
studies O 0
have O 0
shown O 0
a O 0
specific O 0
interaction O 0
on O 0
anxiety B-Disease 0
responses O 0
. O 0

OBJECTIVES O 0
: O 0
The O 0
present O 0
study O 0
investigates O 0
the O 0
effects O 0
of O 0
nicotine B-Chemical 0
on O 0
anxiety B-Disease 0
induced O 0
by O 0
caffeine B-Chemical 0
and O 0
another O 0
anxiogenic O 0
drug O 0
, O 0
pentylenetetrazole B-Chemical 0
, O 0
in O 0
mice O 0
. O 0

The O 0
elevated O 0
plus O 0
- O 0
maze O 0
( O 0
EPM O 0
) O 0
test O 0
was O 0
used O 0
to O 0
evaluate O 0
the O 0
effects O 0
of O 0
drugs O 0
on O 0
anxiety B-Disease 0
. O 0

METHODS O 0
: O 0
Adult O 0
male O 0
Swiss O 0
Webster O 0
mice O 0
( O 0
25 O 0
- O 0
32 O 0
g O 0
) O 0
were O 0
given O 0
nicotine B-Chemical 0
( O 0
0 O 0
. O 0
05 O 0
- O 0
0 O 0
. O 0
25 O 0
mg O 0
/ O 0
kg O 0
s O 0
. O 0
c O 0
. O 0
) O 0
or O 0
saline O 0
10 O 0
min O 0
before O 0
caffeine B-Chemical 0
( O 0
70 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
or O 0
pentylenetetrazole B-Chemical 0
( O 0
15 O 0
and O 0
30 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
injections O 0
. O 0

After O 0
15 O 0
min O 0
, O 0
mice O 0
were O 0
evaluated O 0
for O 0
their O 0
open O 0
- O 0
and O 0
closed O 0
- O 0
arm O 0
time O 0
and O 0
entries O 0
on O 0
the O 0
EPM O 0
for O 0
a O 0
10 O 0
- O 0
min O 0
session O 0
. O 0

Locomotor O 0
activity O 0
was O 0
recorded O 0
for O 0
individual O 0
groups O 0
by O 0
using O 0
the O 0
same O 0
treatment O 0
protocol O 0
with O 0
the O 0
EPM O 0
test O 0
. O 0

RESULTS O 0
: O 0
Nicotine B-Chemical 0
( O 0
0 O 0
. O 0
05 O 0
- O 0
0 O 0
. O 0
25 O 0
mg O 0
/ O 0
kg O 0
) O 0
itself O 0
did O 0
not O 0
produce O 0
any O 0
significant O 0
effect O 0
in O 0
the O 0
EPM O 0
test O 0
, O 0
whereas O 0
caffeine B-Chemical 0
( O 0
70 O 0
mg O 0
/ O 0
kg O 0
) O 0
and O 0
pentylenetetrazole B-Chemical 0
( O 0
30 O 0
mg O 0
/ O 0
kg O 0
) O 0
produced O 0
an O 0
anxiogenic O 0
effect O 0
, O 0
apparent O 0
with O 0
decreases O 0
in O 0
open O 0
- O 0
arm O 0
time O 0
and O 0
entry O 0
. O 0

Nicotine B-Chemical 0
( O 0
0 O 0
. O 0
25 O 0
mg O 0
/ O 0
kg O 0
) O 0
pretreatment O 0
blocked O 0
the O 0
caffeine B-Chemical 0
- O 0
but O 0
not O 0
pentylenetetrazole B-Chemical 0
- O 0
induced O 0
anxiety B-Disease 0
. O 0

Administration O 0
of O 0
each O 0
drug O 0
and O 0
their O 0
combinations O 0
did O 0
not O 0
produce O 0
any O 0
effect O 0
on O 0
locomotor O 0
activity O 0
. O 0

CONCLUSIONS O 0
: O 0
Our O 0
results O 0
suggest O 0
that O 0
the O 0
antagonistic O 0
effect O 0
of O 0
nicotine B-Chemical 0
on O 0
caffeine B-Chemical 0
- O 0
induced O 0
anxiety B-Disease 0
is O 0
specific O 0
to O 0
caffeine B-Chemical 0
, O 0
instead O 0
of O 0
a O 0
non O 0
- O 0
specific O 0
anxiolytic O 0
effect O 0
. O 0

Thus O 0
, O 0
it O 0
may O 0
extend O 0
the O 0
current O 0
findings O 0
on O 0
the O 0
interaction O 0
between O 0
nicotine B-Chemical 0
and O 0
caffeine B-Chemical 0
. O 0

Long O 0
term O 0
hormone O 0
therapy O 0
for O 0
perimenopausal O 0
and O 0
postmenopausal O 0
women O 0
. O 0

BACKGROUND O 0
: O 0
Hormone O 0
therapy O 0
( O 0
HT O 0
) O 0
is O 0
widely O 0
used O 0
for O 0
controlling O 0
menopausal B-Disease 0
symptoms I-Disease 0
. O 0

It O 0
has O 0
also O 0
been O 0
used O 0
for O 0
the O 0
management O 0
and O 0
prevention O 0
of O 0
cardiovascular B-Disease 0
disease I-Disease 0
, O 0
osteoporosis B-Disease 0
and O 0
dementia B-Disease 0
in O 0
older O 0
women O 0
but O 0
the O 0
evidence O 0
supporting O 0
its O 0
use O 0
for O 0
these O 0
indications O 0
is O 0
largely O 0
observational O 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
assess O 0
the O 0
effect O 0
of O 0
long O 0
- O 0
term O 0
HT O 0
on O 0
mortality O 0
, O 0
heart B-Disease 0
disease I-Disease 0
, O 0
venous B-Disease 0
thromboembolism I-Disease 0
, O 0
stroke B-Disease 0
, O 0
transient B-Disease 0
ischaemic I-Disease 0
attacks I-Disease 0
, O 0
breast B-Disease 0
cancer I-Disease 0
, O 0
colorectal B-Disease 0
cancer I-Disease 0
, O 0
ovarian B-Disease 0
cancer I-Disease 0
, O 0
endometrial B-Disease 0
cancer I-Disease 0
, O 0
gallbladder B-Disease 0
disease I-Disease 0
, O 0
cognitive O 0
function O 0
, O 0
dementia B-Disease 0
, O 0
fractures B-Disease 0
and O 0
quality O 0
of O 0
life O 0
. O 0

SEARCH O 0
STRATEGY O 0
: O 0
We O 0
searched O 0
the O 0
following O 0
databases O 0
up O 0
to O 0
November O 0
2004 O 0
: O 0
the O 0
Cochrane O 0
Menstrual O 0
Disorders O 0
and O 0
Subfertility O 0
Group O 0
Trials O 0
Register O 0
, O 0
Cochrane O 0
Central O 0
Register O 0
of O 0
Controlled O 0
Trials O 0
( O 0
CENTRAL O 0
) O 0
, O 0
MEDLINE O 0
, O 0
EMBASE O 0
, O 0
Biological O 0
Abstracts O 0
. O 0

Relevant O 0
non O 0
- O 0
indexed O 0
journals O 0
and O 0
conference O 0
abstracts O 0
were O 0
also O 0
searched O 0
. O 0

SELECTION O 0
CRITERIA O 0
: O 0
Randomised O 0
double O 0
- O 0
blind O 0
trials O 0
of O 0
HT O 0
( O 0
oestrogens B-Chemical 0
with O 0
or O 0
without O 0
progestogens B-Chemical 0
) O 0
versus O 0
placebo O 0
, O 0
taken O 0
for O 0
at O 0
least O 0
one O 0
year O 0
by O 0
perimenopausal O 0
or O 0
postmenopausal O 0
women O 0
. O 0

DATA O 0
COLLECTION O 0
AND O 0
ANALYSIS O 0
: O 0
Fifteen O 0
RCTs O 0
were O 0
included O 0
. O 0

Trials O 0
were O 0
assessed O 0
for O 0
quality O 0
and O 0
two O 0
review O 0
authors O 0
extracted O 0
data O 0
independently O 0
. O 0

They O 0
calculated O 0
risk O 0
ratios O 0
for O 0
dichotomous O 0
outcomes O 0
and O 0
weighted O 0
mean O 0
differences O 0
for O 0
continuous O 0
outcomes O 0
. O 0

Clinical O 0
heterogeneity O 0
precluded O 0
meta O 0
- O 0
analysis O 0
for O 0
most O 0
outcomes O 0
. O 0

MAIN O 0
RESULTS O 0
: O 0
All O 0
the O 0
statistically O 0
significant O 0
results O 0
were O 0
derived O 0
from O 0
the O 0
two O 0
biggest O 0
trials O 0
. O 0

In O 0
relatively O 0
healthy O 0
women O 0
, O 0
combined O 0
continuous O 0
HT O 0
significantly O 0
increased O 0
the O 0
risk O 0
of O 0
venous B-Disease 0
thromboembolism I-Disease 0
or O 0
coronary O 0
event O 0
( O 0
after O 0
one O 0
year O 0
' O 0
s O 0
use O 0
) O 0
, O 0
stroke B-Disease 0
( O 0
after O 0
3 O 0
years O 0
) O 0
, O 0
breast B-Disease 0
cancer I-Disease 0
( O 0
after O 0
5 O 0
years O 0
) O 0
and O 0
gallbladder B-Disease 0
disease I-Disease 0
. O 0

Long O 0
- O 0
term O 0
oestrogen B-Chemical 0
- O 0
only O 0
HT O 0
also O 0
significantly O 0
increased O 0
the O 0
risk O 0
of O 0
stroke B-Disease 0
and O 0
gallbladder B-Disease 0
disease I-Disease 0
. O 0

Overall O 0
, O 0
the O 0
only O 0
statistically O 0
significant O 0
benefits O 0
of O 0
HT O 0
were O 0
a O 0
decreased O 0
incidence O 0
of O 0
fractures B-Disease 0
and O 0
colon B-Disease 0
cancer I-Disease 0
with O 0
long O 0
- O 0
term O 0
use O 0
. O 0

Among O 0
relatively O 0
healthy O 0
women O 0
over O 0
65 O 0
years O 0
taking O 0
continuous O 0
combined O 0
HT O 0
, O 0
there O 0
was O 0
a O 0
statistically O 0
significant O 0
increase O 0
in O 0
the O 0
incidence O 0
of O 0
dementia B-Disease 0
. O 0

Among O 0
women O 0
with O 0
cardiovascular B-Disease 0
disease I-Disease 0
, O 0
long O 0
- O 0
term O 0
use O 0
of O 0
combined O 0
continuous O 0
HT O 0
significantly O 0
increased O 0
the O 0
risk O 0
of O 0
venous B-Disease 0
thromboembolism I-Disease 0
. O 0

No O 0
trials O 0
focussed O 0
specifically O 0
on O 0
younger O 0
women O 0
. O 0

However O 0
, O 0
one O 0
trial O 0
analysed O 0
subgroups O 0
of O 0
2839 O 0
relatively O 0
healthy O 0
50 O 0
to O 0
59 O 0
year O 0
- O 0
old O 0
women O 0
taking O 0
combined O 0
continuous O 0
HT O 0
and O 0
1637 O 0
taking O 0
oestrogen B-Chemical 0
- O 0
only O 0
HT O 0
, O 0
versus O 0
similar O 0
- O 0
sized O 0
placebo O 0
groups O 0
. O 0

The O 0
only O 0
significantly O 0
increased O 0
risk O 0
reported O 0
was O 0
for O 0
venous B-Disease 0
thromboembolism I-Disease 0
in O 0
women O 0
taking O 0
combined O 0
continuous O 0
HT O 0
; O 0
their O 0
absolute O 0
risk O 0
remained O 0
very O 0
low O 0
. O 0

AUTHORS O 0
' O 0
CONCLUSIONS O 0
: O 0
HT O 0
is O 0
not O 0
indicated O 0
for O 0
the O 0
routine O 0
management O 0
of O 0
chronic B-Disease 0
disease I-Disease 0
. O 0

We O 0
need O 0
more O 0
evidence O 0
on O 0
the O 0
safety O 0
of O 0
HT O 0
for O 0
menopausal O 0
symptom O 0
control O 0
, O 0
though O 0
short O 0
- O 0
term O 0
use O 0
appears O 0
to O 0
be O 0
relatively O 0
safe O 0
for O 0
healthy O 0
younger O 0
women O 0
. O 0

Drug B-Disease 0
- I-Disease 0
induced I-Disease 0
liver I-Disease 0
injury I-Disease 0
: O 0
an O 0
analysis O 0
of O 0
461 O 0
incidences O 0
submitted O 0
to O 0
the O 0
Spanish O 0
registry O 0
over O 0
a O 0
10 O 0
- O 0
year O 0
period O 0
. O 0

BACKGROUND O 0
& O 0
AIMS O 0
: O 0
Progress O 0
in O 0
the O 0
understanding O 0
of O 0
susceptibility O 0
factors O 0
to O 0
drug B-Disease 0
- I-Disease 0
induced I-Disease 0
liver I-Disease 0
injury I-Disease 0
( O 0
DILI B-Disease 0
) O 0
and O 0
outcome O 0
predictability O 0
are O 0
hampered O 0
by O 0
the O 0
lack O 0
of O 0
systematic O 0
programs O 0
to O 0
detect O 0
bona O 0
fide O 0
cases O 0
. O 0

METHODS O 0
: O 0
A O 0
cooperative O 0
network O 0
was O 0
created O 0
in O 0
1994 O 0
in O 0
Spain O 0
to O 0
identify O 0
all O 0
suspicions O 0
of O 0
DILI B-Disease 0
following O 0
a O 0
prospective O 0
structured O 0
report O 0
form O 0
. O 0

The O 0
liver B-Disease 0
damage I-Disease 0
was O 0
characterized O 0
according O 0
to O 0
hepatocellular O 0
, O 0
cholestatic B-Disease 0
, O 0
and O 0
mixed O 0
laboratory O 0
criteria O 0
and O 0
to O 0
histologic O 0
criteria O 0
when O 0
available O 0
. O 0

Further O 0
evaluation O 0
of O 0
causality O 0
assessment O 0
was O 0
centrally O 0
performed O 0
. O 0

RESULTS O 0
: O 0
Since O 0
April O 0
1994 O 0
to O 0
August O 0
2004 O 0
, O 0
461 O 0
out O 0
of O 0
570 O 0
submitted O 0
cases O 0
, O 0
involving O 0
505 O 0
drugs O 0
, O 0
were O 0
deemed O 0
to O 0
be O 0
related O 0
to O 0
DILI B-Disease 0
. O 0

The O 0
antiinfective O 0
group O 0
of O 0
drugs O 0
was O 0
the O 0
more O 0
frequently O 0
incriminated O 0
, O 0
amoxicillin B-Chemical 0
- I-Chemical 0
clavulanate I-Chemical 0
accounting O 0
for O 0
the O 0
12 O 0
. O 0
8 O 0
% O 0
of O 0
the O 0
whole O 0
series O 0
. O 0

The O 0
hepatocellular O 0
pattern O 0
of O 0
damage O 0
was O 0
the O 0
most O 0
common O 0
( O 0
58 O 0
% O 0
) O 0
, O 0
was O 0
inversely O 0
correlated O 0
with O 0
age O 0
( O 0
P O 0
< O 0
. O 0
0001 O 0
) O 0
, O 0
and O 0
had O 0
the O 0
worst O 0
outcome O 0
( O 0
Cox O 0
regression O 0
, O 0
P O 0
< O 0
. O 0
034 O 0
) O 0
. O 0

Indeed O 0
, O 0
the O 0
incidence O 0
of O 0
liver O 0
transplantation O 0
and O 0
death O 0
in O 0
this O 0
group O 0
was O 0
11 O 0
. O 0
7 O 0
% O 0
if O 0
patients O 0
had O 0
jaundice B-Disease 0
at O 0
presentation O 0
, O 0
whereas O 0
the O 0
corresponding O 0
figure O 0
was O 0
3 O 0
. O 0
8 O 0
% O 0
in O 0
nonjaundiced O 0
patients O 0
( O 0
P O 0
< O 0
. O 0
04 O 0
) O 0
. O 0

Factors O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
fulminant B-Disease 0
hepatic I-Disease 0
failure I-Disease 0
were O 0
female O 0
sex O 0
( O 0
OR O 0
= O 0
25 O 0
; O 0
95 O 0
% O 0
CI O 0
: O 0
4 O 0
. O 0
1 O 0
- O 0
151 O 0
; O 0
P O 0
< O 0
. O 0
0001 O 0
) O 0
, O 0
hepatocellular O 0
damage O 0
( O 0
OR O 0
= O 0
7 O 0
. O 0
9 O 0
; O 0
95 O 0
% O 0
CI O 0
: O 0
1 O 0
. O 0
6 O 0
- O 0
37 O 0
; O 0
P O 0
< O 0
. O 0
009 O 0
) O 0
, O 0
and O 0
higher O 0
baseline O 0
plasma O 0
bilirubin B-Chemical 0
value O 0
( O 0
OR O 0
= O 0
1 O 0
. O 0
15 O 0
; O 0
95 O 0
% O 0
CI O 0
: O 0
1 O 0
. O 0
09 O 0
- O 0
1 O 0
. O 0
22 O 0
; O 0
P O 0
< O 0
. O 0
0001 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Patients O 0
with O 0
drug O 0
- O 0
induced O 0
hepatocellular O 0
jaundice B-Disease 0
have O 0
11 O 0
. O 0
7 O 0
% O 0
chance O 0
of O 0
progressing O 0
to O 0
death O 0
or O 0
transplantation O 0
. O 0

Amoxicillin B-Chemical 0
- I-Chemical 0
clavulanate I-Chemical 0
stands O 0
out O 0
as O 0
the O 0
most O 0
common O 0
drug O 0
related O 0
to O 0
DILI B-Disease 0
. O 0

Morphological O 0
evaluation O 0
of O 0
the O 0
effect O 0
of O 0
d B-Chemical 0
- I-Chemical 0
ribose I-Chemical 0
on O 0
adriamycin B-Chemical 0
- O 0
evoked O 0
cardiotoxicity B-Disease 0
in O 0
rats O 0
. O 0

The O 0
influence O 0
of O 0
d B-Chemical 0
- I-Chemical 0
ribose I-Chemical 0
on O 0
adriamycin B-Chemical 0
- O 0
induced O 0
myocardiopathy B-Disease 0
in O 0
rats O 0
was O 0
studied O 0
. O 0

Adriamycin B-Chemical 0
in O 0
the O 0
cumulative O 0
dose O 0
of O 0
25 O 0
mg O 0
/ O 0
kg O 0
evoked O 0
fully O 0
developed O 0
cardiac B-Disease 0
toxicity I-Disease 0
. O 0

D B-Chemical 0
- I-Chemical 0
ribose I-Chemical 0
in O 0
the O 0
multiple O 0
doses O 0
of O 0
200 O 0
mg O 0
/ O 0
kg O 0
did O 0
not O 0
influence O 0
ADR B-Chemical 0
cardiotoxicity B-Disease 0
. O 0

In O 0
vivo O 0
evidences O 0
suggesting O 0
the O 0
role O 0
of O 0
oxidative O 0
stress O 0
in O 0
pathogenesis O 0
of O 0
vancomycin B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
: O 0
protection O 0
by O 0
erdosteine B-Chemical 0
. O 0

The O 0
aims O 0
of O 0
this O 0
study O 0
were O 0
to O 0
examine O 0
vancomycin B-Chemical 0
( O 0
VCM B-Chemical 0
) O 0
- O 0
induced O 0
oxidative O 0
stress O 0
that O 0
promotes O 0
production O 0
of O 0
reactive O 0
oxygen B-Chemical 0
species O 0
( O 0
ROS O 0
) O 0
and O 0
to O 0
investigate O 0
the O 0
role O 0
of O 0
erdosteine B-Chemical 0
, O 0
an O 0
expectorant O 0
agent O 0
, O 0
which O 0
has O 0
also O 0
antioxidant O 0
properties O 0
, O 0
on O 0
kidney O 0
tissue O 0
against O 0
the O 0
possible O 0
VCM B-Chemical 0
- O 0
induced O 0
renal B-Disease 0
impairment I-Disease 0
in O 0
rats O 0
. O 0

Rats O 0
were O 0
divided O 0
into O 0
three O 0
groups O 0
: O 0
sham O 0
, O 0
VCM B-Chemical 0
and O 0
VCM B-Chemical 0
plus O 0
erdosteine B-Chemical 0
. O 0

VCM B-Chemical 0
was O 0
administrated O 0
intraperitoneally O 0
( O 0
i O 0
. O 0
p O 0
. O 0
) O 0
with O 0
200mgkg O 0
( O 0
- O 0
1 O 0
) O 0
twice O 0
daily O 0
for O 0
7 O 0
days O 0
. O 0

Erdosteine B-Chemical 0
was O 0
administered O 0
orally O 0
. O 0

VCM B-Chemical 0
administration O 0
to O 0
control O 0
rats O 0
significantly O 0
increased O 0
renal O 0
malondialdehyde B-Chemical 0
( O 0
MDA B-Chemical 0
) O 0
and O 0
urinary O 0
N O 0
- O 0
acetyl O 0
- O 0
beta O 0
- O 0
d O 0
- O 0
glucosaminidase O 0
( O 0
NAG O 0
, O 0
a O 0
marker O 0
of O 0
renal B-Disease 0
tubular I-Disease 0
injury I-Disease 0
) O 0
excretion O 0
but O 0
decreased O 0
superoxide B-Chemical 0
dismutase O 0
( O 0
SOD O 0
) O 0
and O 0
catalase O 0
( O 0
CAT O 0
) O 0
activities O 0
. O 0

Erdosteine B-Chemical 0
administration O 0
with O 0
VCM B-Chemical 0
injections O 0
caused O 0
significantly O 0
decreased O 0
renal O 0
MDA B-Chemical 0
and O 0
urinary O 0
NAG O 0
excretion O 0
, O 0
and O 0
increased O 0
SOD O 0
activity O 0
, O 0
but O 0
not O 0
CAT O 0
activity O 0
in O 0
renal O 0
tissue O 0
when O 0
compared O 0
with O 0
VCM B-Chemical 0
alone O 0
. O 0

Erdosteine B-Chemical 0
showed O 0
histopathological O 0
protection O 0
against O 0
VCM B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
. O 0

There O 0
were O 0
a O 0
significant O 0
dilatation O 0
of O 0
tubular O 0
lumens O 0
, O 0
extensive O 0
epithelial O 0
cell O 0
vacuolization O 0
, O 0
atrophy B-Disease 0
, O 0
desquamation B-Disease 0
, O 0
and O 0
necrosis B-Disease 0
in O 0
VCM B-Chemical 0
- O 0
treated O 0
rats O 0
more O 0
than O 0
those O 0
of O 0
the O 0
control O 0
and O 0
the O 0
erdosteine B-Chemical 0
groups O 0
. O 0

Erdosteine B-Chemical 0
caused O 0
a O 0
marked O 0
reduction O 0
in O 0
the O 0
extent O 0
of O 0
tubular O 0
damage O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
oxidative O 0
tubular O 0
damage O 0
plays O 0
an O 0
important O 0
role O 0
in O 0
the O 0
VCM B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
and O 0
the O 0
modulation O 0
of O 0
oxidative O 0
stress O 0
with O 0
erdosteine B-Chemical 0
reduces O 0
the O 0
VCM B-Chemical 0
- O 0
induced O 0
kidney B-Disease 0
damage I-Disease 0
both O 0
at O 0
the O 0
biochemical O 0
and O 0
histological O 0
levels O 0
. O 0

Gemfibrozil B-Chemical 0
- O 0
lovastatin B-Chemical 0
therapy O 0
for O 0
primary O 0
hyperlipoproteinemias B-Disease 0
. O 0

The O 0
specific O 0
aim O 0
of O 0
this O 0
retrospective O 0
, O 0
observational O 0
study O 0
was O 0
to O 0
assess O 0
safety O 0
and O 0
efficacy O 0
of O 0
long O 0
- O 0
term O 0
( O 0
21 O 0
months O 0
/ O 0
patient O 0
) O 0
, O 0
open O 0
- O 0
label O 0
, O 0
gemfibrozil B-Chemical 0
- O 0
lovastatin B-Chemical 0
treatment O 0
in O 0
80 O 0
patients O 0
with O 0
primary O 0
mixed O 0
hyperlipidemia B-Disease 0
( O 0
68 O 0
% O 0
of O 0
whom O 0
had O 0
atherosclerotic B-Disease 0
vascular I-Disease 0
disease I-Disease 0
) O 0
. O 0

Because O 0
ideal O 0
lipid O 0
targets O 0
were O 0
not O 0
reached O 0
( O 0
low O 0
- O 0
density O 0
lipoprotein O 0
( O 0
LDL O 0
) O 0
cholesterol B-Chemical 0
less O 0
than O 0
130 O 0
mg O 0
/ O 0
dl O 0
, O 0
high O 0
- O 0
density O 0
lipoprotein O 0
( O 0
HDL O 0
) O 0
cholesterol B-Chemical 0
greater O 0
than O 0
35 O 0
mg O 0
/ O 0
dl O 0
, O 0
or O 0
total O 0
cholesterol B-Chemical 0
/ O 0
HDL O 0
cholesterol B-Chemical 0
less O 0
than O 0
4 O 0
. O 0
5 O 0
mg O 0
/ O 0
dl O 0
) O 0
with O 0
diet O 0
plus O 0
a O 0
single O 0
drug O 0
, O 0
gemfibrozil B-Chemical 0
( O 0
1 O 0
. O 0
2 O 0
g O 0
/ O 0
day O 0
) O 0
- O 0
lovastatin B-Chemical 0
( O 0
primarily O 0
20 O 0
or O 0
40 O 0
mg O 0
) O 0
treatment O 0
was O 0
given O 0
. O 0

Follow O 0
- O 0
up O 0
visits O 0
were O 0
scheduled O 0
with O 0
2 O 0
- O 0
drug O 0
therapy O 0
every O 0
6 O 0
to O 0
8 O 0
weeks O 0
, O 0
an O 0
average O 0
of O 0
10 O 0
. O 0
3 O 0
visits O 0
per O 0
patient O 0
, O 0
with O 0
741 O 0
batteries O 0
of O 0
6 O 0
liver O 0
function O 0
tests O 0
and O 0
714 O 0
creatine B-Chemical 0
phosphokinase O 0
levels O 0
measured O 0
. O 0

Only O 0
1 O 0
of O 0
the O 0
4 O 0
, O 0
446 O 0
liver O 0
function O 0
tests O 0
( O 0
0 O 0
. O 0
02 O 0
% O 0
) O 0
, O 0
a O 0
gamma O 0
glutamyl O 0
transferase O 0
, O 0
was O 0
greater O 0
than O 0
or O 0
equal O 0
to O 0
3 O 0
times O 0
the O 0
upper O 0
normal O 0
limit O 0
. O 0

Of O 0
the O 0
714 O 0
creatine B-Chemical 0
phosphokinase O 0
levels O 0
, O 0
9 O 0
% O 0
were O 0
high O 0
; O 0
only O 0
1 O 0
( O 0
0 O 0
. O 0
1 O 0
% O 0
) O 0
was O 0
greater O 0
than O 0
or O 0
equal O 0
to O 0
3 O 0
times O 0
the O 0
upper O 0
normal O 0
limit O 0
. O 0

With O 0
2 O 0
- O 0
drug O 0
therapy O 0
, O 0
mean O 0
total O 0
cholesterol B-Chemical 0
decreased O 0
22 O 0
% O 0
from O 0
255 O 0
to O 0
200 O 0
mg O 0
/ O 0
dl O 0
, O 0
triglyceride B-Chemical 0
levels O 0
decreased O 0
35 O 0
% O 0
from O 0
236 O 0
to O 0
154 O 0
mg O 0
/ O 0
dl O 0
, O 0
LDL O 0
cholesterol B-Chemical 0
decreased O 0
26 O 0
% O 0
from O 0
176 O 0
to O 0
131 O 0
mg O 0
/ O 0
dl O 0
, O 0
and O 0
the O 0
total O 0
cholesterol B-Chemical 0
/ O 0
HDL O 0
cholesterol B-Chemical 0
ratio O 0
decreased O 0
24 O 0
% O 0
from O 0
7 O 0
. O 0
1 O 0
to O 0
5 O 0
. O 0
4 O 0
, O 0
all O 0
p O 0
less O 0
than O 0
or O 0
equal O 0
to O 0
0 O 0
. O 0
0001 O 0
. O 0

Myositis B-Disease 0
, O 0
attributable O 0
to O 0
the O 0
drug O 0
combination O 0
and O 0
symptomatic O 0
enough O 0
to O 0
discontinue O 0
it O 0
, O 0
occurred O 0
in O 0
3 O 0
% O 0
of O 0
patients O 0
, O 0
and O 0
in O 0
1 O 0
% O 0
with O 0
concurrent O 0
high O 0
creatine B-Chemical 0
phosphokinase O 0
( O 0
769 O 0
U O 0
/ O 0
liter O 0
) O 0
; O 0
no O 0
patients O 0
had O 0
rhabdomyolysis B-Disease 0
or O 0
myoglobinuria B-Disease 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Does O 0
domperidone B-Chemical 0
potentiate O 0
mirtazapine B-Chemical 0
- O 0
associated O 0
restless B-Disease 0
legs I-Disease 0
syndrome I-Disease 0
? O 0

There O 0
is O 0
now O 0
evidence O 0
to O 0
suggest O 0
a O 0
central O 0
role O 0
for O 0
the O 0
dopaminergic O 0
system O 0
in O 0
restless B-Disease 0
legs I-Disease 0
syndrome I-Disease 0
( O 0
RLS B-Disease 0
) O 0
. O 0

For O 0
example O 0
, O 0
the O 0
symptoms O 0
of O 0
RLS B-Disease 0
can O 0
be O 0
dramatically O 0
improved O 0
by O 0
levodopa B-Chemical 0
and O 0
dopamine B-Chemical 0
agonists O 0
, O 0
whereas O 0
central O 0
dopamine B-Chemical 0
D2 O 0
receptor O 0
antagonists O 0
can O 0
induce O 0
or O 0
aggravate O 0
RLS B-Disease 0
symptoms O 0
. O 0

To O 0
our O 0
knowledge O 0
, O 0
there O 0
is O 0
no O 0
previous O 0
report O 0
regarding O 0
whether O 0
domperidone B-Chemical 0
, O 0
a O 0
peripheral O 0
dopamine B-Chemical 0
D2 O 0
receptor O 0
antagonist O 0
, O 0
can O 0
also O 0
induce O 0
or O 0
aggravate O 0
symptoms O 0
of O 0
RLS B-Disease 0
. O 0

Mirtazapine B-Chemical 0
, O 0
the O 0
first O 0
noradrenergic O 0
and O 0
specific O 0
serotonergic O 0
antidepressant O 0
( O 0
NaSSA O 0
) O 0
, O 0
has O 0
been O 0
associated O 0
with O 0
RLS B-Disease 0
in O 0
several O 0
recent O 0
publications O 0
. O 0

The O 0
authors O 0
report O 0
here O 0
a O 0
depressed O 0
patient O 0
comorbid O 0
with O 0
postprandial B-Disease 0
dyspepsia I-Disease 0
who O 0
developed O 0
RLS B-Disease 0
after O 0
mirtazapine B-Chemical 0
had O 0
been O 0
added O 0
to O 0
his O 0
domperidone B-Chemical 0
therapy O 0
. O 0

Our O 0
patient O 0
started O 0
to O 0
have O 0
symptoms O 0
of O 0
RLS B-Disease 0
only O 0
after O 0
he O 0
had O 0
been O 0
treated O 0
with O 0
mirtazapine B-Chemical 0
, O 0
and O 0
his O 0
RLS B-Disease 0
symptoms O 0
resolved O 0
completely O 0
upon O 0
discontinuation O 0
of O 0
his O 0
mirtazapine B-Chemical 0
. O 0

Such O 0
a O 0
temporal O 0
relationship O 0
between O 0
the O 0
use O 0
of O 0
mirtazapine B-Chemical 0
and O 0
the O 0
symptoms O 0
of O 0
RLS B-Disease 0
in O 0
our O 0
patient O 0
did O 0
not O 0
support O 0
a O 0
potentiating O 0
effect O 0
of O 0
domperione B-Chemical 0
on O 0
mirtazapine B-Chemical 0
- O 0
associated O 0
RLS B-Disease 0
. O 0

However O 0
, O 0
physicians O 0
should O 0
be O 0
aware O 0
of O 0
the O 0
possibility O 0
that O 0
mirtazapine B-Chemical 0
can O 0
be O 0
associated O 0
with O 0
RLS B-Disease 0
in O 0
some O 0
individuals O 0
, O 0
especially O 0
those O 0
receiving O 0
concomitant O 0
dopamine B-Chemical 0
D2 O 0
receptor O 0
antagonists O 0
. O 0

Antiandrogenic O 0
therapy O 0
can O 0
cause O 0
coronary B-Disease 0
arterial I-Disease 0
disease I-Disease 0
. O 0

AIM O 0
: O 0
To O 0
study O 0
the O 0
change O 0
of O 0
lipid O 0
metabolism O 0
by O 0
antiandrogen O 0
therapy O 0
in O 0
patients O 0
with O 0
prostate B-Disease 0
cancer I-Disease 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
We O 0
studied O 0
with O 0
a O 0
2 O 0
. O 0
5 O 0
years O 0
follow O 0
- O 0
up O 0
the O 0
changes O 0
in O 0
plasma O 0
cholesterols B-Chemical 0
( O 0
C B-Chemical 0
) O 0
, O 0
triglycerides B-Chemical 0
( O 0
TG B-Chemical 0
) O 0
, O 0
lipoproteins O 0
( O 0
LP O 0
) O 0
, O 0
and O 0
apolipoproteins O 0
( O 0
Apo O 0
) O 0
B O 0
- O 0
100 O 0
, O 0
A O 0
- O 0
I O 0
, O 0
and O 0
A O 0
- O 0
II O 0
pro O 0
fi O 0
les O 0
in O 0
24 O 0
patients O 0
of O 0
mean O 0
age O 0
60 O 0
years O 0
with O 0
low O 0
risk O 0
prostate B-Disease 0
cancer I-Disease 0
( O 0
stage O 0
: O 0
T1cN0M0 O 0
, O 0
Gleason O 0
score O 0
: O 0
2 O 0
- O 0
5 O 0
) O 0
during O 0
treatment O 0
with O 0
cyproterone B-Chemical 0
acetate I-Chemical 0
( O 0
CPA B-Chemical 0
) O 0
without O 0
surgical O 0
management O 0
or O 0
radiation O 0
therapy O 0
. O 0

RESULTS O 0
: O 0
Significant O 0
decreases O 0
of O 0
HDL O 0
- O 0
C O 0
, O 0
Apo O 0
A O 0
- O 0
I O 0
and O 0
Apo O 0
A O 0
- O 0
II O 0
and O 0
an O 0
increase O 0
of O 0
triglyceride B-Chemical 0
levels O 0
in O 0
VLDL O 0
were O 0
induced O 0
by O 0
CPA B-Chemical 0
. O 0

After O 0
a O 0
period O 0
of O 0
2 O 0
. O 0
5 O 0
years O 0
on O 0
CPA B-Chemical 0
treatment O 0
, O 0
four O 0
patients O 0
out O 0
of O 0
twenty O 0
- O 0
four O 0
were O 0
found O 0
to O 0
be O 0
affected O 0
by O 0
coronary B-Disease 0
heart I-Disease 0
disease I-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
Ischaemic O 0
coronary B-Disease 0
arteriosclerosis I-Disease 0
with O 0
an O 0
incidence O 0
rate O 0
of O 0
16 O 0
. O 0
6 O 0
% O 0
as O 0
caused O 0
by O 0
prolonged O 0
CPA B-Chemical 0
therapy O 0
is O 0
mediated O 0
through O 0
changes O 0
in O 0
HDL O 0
cholesterol B-Chemical 0
, O 0
Apo O 0
A O 0
- O 0
I O 0
and O 0
Apo O 0
A O 0
- O 0
II O 0
pro O 0
fi O 0
les O 0
, O 0
other O 0
than O 0
the O 0
well O 0
- O 0
known O 0
hyperglyceridemic B-Disease 0
effect I-Disease 0
caused O 0
by O 0
estrogen B-Chemical 0
. O 0

5 B-Chemical 0
- I-Chemical 0
Fluorouracil I-Chemical 0
cardiotoxicity B-Disease 0
induced O 0
by O 0
alpha B-Chemical 0
- I-Chemical 0
fluoro I-Chemical 0
- I-Chemical 0
beta I-Chemical 0
- I-Chemical 0
alanine I-Chemical 0
. O 0

Cardiotoxicity B-Disease 0
is O 0
a O 0
rare O 0
complication O 0
occurring O 0
during O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
( O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
) O 0
treatment O 0
for O 0
malignancies B-Disease 0
. O 0

We O 0
herein O 0
report O 0
the O 0
case O 0
of O 0
a O 0
70 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
, O 0
in O 0
whom O 0
a O 0
high O 0
serum O 0
level O 0
of O 0
alpha B-Chemical 0
- I-Chemical 0
fluoro I-Chemical 0
- I-Chemical 0
beta I-Chemical 0
- I-Chemical 0
alanine I-Chemical 0
( O 0
FBAL B-Chemical 0
) O 0
was O 0
observed O 0
. O 0

The O 0
patient O 0
, O 0
who O 0
had O 0
unresectable O 0
colon B-Disease 0
cancer I-Disease 0
metastases O 0
to O 0
the O 0
liver O 0
and O 0
lung O 0
, O 0
was O 0
referred O 0
to O 0
us O 0
for O 0
chemotherapy O 0
from O 0
an O 0
affiliated O 0
hospital O 0
; O 0
he O 0
had O 0
no O 0
cardiac O 0
history O 0
. O 0

After O 0
admission O 0
, O 0
the O 0
patient O 0
received O 0
a O 0
continuous O 0
intravenous O 0
infusion O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
( O 0
1000 O 0
mg O 0
/ O 0
day O 0
) O 0
, O 0
during O 0
which O 0
precordial B-Disease 0
pain I-Disease 0
with O 0
right B-Disease 0
bundle I-Disease 0
branch I-Disease 0
block I-Disease 0
occurred O 0
concomitantly O 0
with O 0
a O 0
high O 0
serum O 0
FBAL B-Chemical 0
concentration O 0
of O 0
1955 O 0
ng O 0
/ O 0
ml O 0
. O 0

Both O 0
the O 0
precordial B-Disease 0
pain I-Disease 0
and O 0
the O 0
electrocardiographic O 0
changes O 0
disappeared O 0
spontaneously O 0
after O 0
the O 0
discontinuation O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
. O 0

As O 0
the O 0
precordial B-Disease 0
pain I-Disease 0
in O 0
this O 0
patient O 0
was O 0
considered O 0
to O 0
have O 0
been O 0
due O 0
to O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
, O 0
the O 0
administration O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
was O 0
abandoned O 0
. O 0

Instead O 0
, O 0
oral O 0
administration O 0
of O 0
S O 0
- O 0
1 O 0
( O 0
a O 0
derivative O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
) O 0
, O 0
at O 0
200 O 0
mg O 0
/ O 0
day O 0
twice O 0
a O 0
week O 0
, O 0
was O 0
instituted O 0
, O 0
because O 0
S O 0
- O 0
1 O 0
has O 0
a O 0
strong O 0
inhibitory O 0
effect O 0
on O 0
dihydropyrimidine B-Chemical 0
dehydrogenase O 0
, O 0
which O 0
catalyzes O 0
the O 0
degradative O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
into O 0
FBAL B-Chemical 0
. O 0

The O 0
serum O 0
FBAL B-Chemical 0
concentration O 0
subsequently O 0
decreased O 0
to O 0
352 O 0
ng O 0
/ O 0
ml O 0
, O 0
the O 0
same O 0
as O 0
the O 0
value O 0
measured O 0
on O 0
the O 0
first O 0
day O 0
of O 0
S O 0
- O 0
1 O 0
administration O 0
. O 0

Thereafter O 0
, O 0
no O 0
cardiac B-Disease 0
symptoms I-Disease 0
were O 0
observed O 0
. O 0

The O 0
patient O 0
achieved O 0
a O 0
partial O 0
response O 0
6 O 0
months O 0
after O 0
the O 0
initiation O 0
of O 0
the O 0
S O 0
- O 0
1 O 0
treatment O 0
. O 0

The O 0
experience O 0
of O 0
this O 0
case O 0
, O 0
together O 0
with O 0
a O 0
review O 0
of O 0
the O 0
literature O 0
, O 0
suggests O 0
that O 0
FBAL B-Chemical 0
is O 0
related O 0
to O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

S O 0
- O 0
1 O 0
may O 0
be O 0
administered O 0
safely O 0
to O 0
patients O 0
with O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

Hepatocellular B-Disease 0
carcinoma I-Disease 0
in O 0
Fanconi B-Disease 0
' I-Disease 0
s I-Disease 0
anemia I-Disease 0
treated O 0
with O 0
androgen B-Chemical 0
and O 0
corticosteroid B-Chemical 0
. O 0

The O 0
case O 0
of O 0
an O 0
11 O 0
- O 0
year O 0
- O 0
old O 0
boy O 0
is O 0
reported O 0
who O 0
was O 0
known O 0
to O 0
have O 0
Fanconi B-Disease 0
' I-Disease 0
s I-Disease 0
anemia I-Disease 0
for O 0
3 O 0
years O 0
and O 0
was O 0
treated O 0
with O 0
androgens B-Chemical 0
, O 0
corticosteroids B-Chemical 0
and O 0
transfusions O 0
. O 0

Two O 0
weeks O 0
before O 0
his O 0
death O 0
he O 0
was O 0
readmitted O 0
because O 0
of O 0
aplastic O 0
crisis O 0
with O 0
septicemia B-Disease 0
and O 0
marked O 0
abnormalities O 0
in O 0
liver O 0
function O 0
and O 0
died O 0
of O 0
hemorrhagic B-Disease 0
bronchopneumonia I-Disease 0
. O 0

At O 0
autopsy O 0
peliosis B-Disease 0
and O 0
multiple O 0
hepatic B-Disease 0
tumors I-Disease 0
were O 0
found O 0
which O 0
histologically O 0
proved O 0
to O 0
be O 0
well O 0
- O 0
differentiated O 0
hepatocellular B-Disease 0
carcinoma I-Disease 0
. O 0

This O 0
case O 0
contributes O 0
to O 0
the O 0
previous O 0
observations O 0
that O 0
non O 0
- O 0
metastasizing O 0
hepatic B-Disease 0
neoplasms I-Disease 0
and O 0
peliosis B-Disease 0
can O 0
develop O 0
in O 0
patients O 0
with O 0
androgen B-Chemical 0
- O 0
and O 0
corticosteroid B-Chemical 0
- O 0
treated O 0
Fanconi B-Disease 0
' I-Disease 0
s I-Disease 0
anemia I-Disease 0
. O 0

The O 0
influence O 0
of O 0
the O 0
time O 0
interval O 0
between O 0
monoHER B-Chemical 0
and O 0
doxorubicin B-Chemical 0
administration O 0
on O 0
the O 0
protection O 0
against O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
in O 0
mice O 0
. O 0

PURPOSE O 0
: O 0
Despite O 0
its O 0
well O 0
- O 0
known O 0
cardiotoxicity B-Disease 0
, O 0
the O 0
anthracyclin O 0
doxorubicin B-Chemical 0
( O 0
DOX B-Chemical 0
) O 0
continues O 0
to O 0
be O 0
an O 0
effective O 0
and O 0
widely O 0
used O 0
chemotherapeutic O 0
agent O 0
. O 0

DOX B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
damage I-Disease 0
presumably O 0
results O 0
from O 0
the O 0
formation O 0
of O 0
free O 0
radicals O 0
by O 0
DOX B-Chemical 0
. O 0

Reactive O 0
oxygen B-Chemical 0
species O 0
particularly O 0
affect O 0
the O 0
cardiac O 0
myocytes O 0
because O 0
these O 0
cells O 0
seem O 0
to O 0
have O 0
a O 0
relatively O 0
poor O 0
antioxidant O 0
defense O 0
system O 0
. O 0

The O 0
semisynthetic O 0
flavonoid B-Chemical 0
monohydroxyethylrutoside B-Chemical 0
( O 0
monoHER B-Chemical 0
) O 0
showed O 0
cardioprotection O 0
against O 0
DOX B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
through O 0
its O 0
radical O 0
scavenging O 0
and O 0
iron B-Chemical 0
chelating O 0
properties O 0
. O 0

Because O 0
of O 0
the O 0
relatively O 0
short O 0
final O 0
half O 0
- O 0
life O 0
of O 0
monoHER B-Chemical 0
( O 0
about O 0
30 O 0
min O 0
) O 0
, O 0
it O 0
is O 0
expected O 0
that O 0
the O 0
time O 0
interval O 0
between O 0
monoHER B-Chemical 0
and O 0
DOX B-Chemical 0
might O 0
be O 0
of O 0
influence O 0
on O 0
the O 0
cardioprotective O 0
effect O 0
of O 0
monoHER B-Chemical 0
. O 0

Therefore O 0
, O 0
the O 0
aim O 0
of O 0
the O 0
present O 0
study O 0
was O 0
to O 0
investigate O 0
this O 0
possible O 0
effect O 0
. O 0

METHODS O 0
: O 0
Six O 0
groups O 0
of O 0
6 O 0
BALB O 0
/ O 0
c O 0
mice O 0
were O 0
treated O 0
with O 0
saline O 0
, O 0
DOX B-Chemical 0
alone O 0
or O 0
DOX B-Chemical 0
( O 0
4 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
) O 0
preceded O 0
by O 0
monoHER B-Chemical 0
( O 0
500 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
with O 0
an O 0
interval O 0
of O 0
10 O 0
, O 0
30 O 0
, O 0
60 O 0
or O 0
120 O 0
min O 0
. O 0

After O 0
a O 0
6 O 0
- O 0
week O 0
treatment O 0
period O 0
and O 0
additional O 0
observation O 0
for O 0
2 O 0
weeks O 0
, O 0
the O 0
mice O 0
were O 0
sacrificed O 0
. O 0

Their O 0
cardiac O 0
tissues O 0
were O 0
processed O 0
for O 0
light O 0
microscopy O 0
, O 0
after O 0
which O 0
cardiomyocyte B-Disease 0
damage I-Disease 0
was O 0
evaluated O 0
according O 0
to O 0
Billingham O 0
( O 0
in O 0
Cancer B-Disease 0
Treat O 0
Rep O 0
62 O 0
( O 0
6 O 0
) O 0
: O 0
865 O 0
- O 0
872 O 0
, O 0
1978 O 0
) O 0
. O 0

Microscopic O 0
evaluation O 0
revealed O 0
that O 0
treatment O 0
with O 0
DOX B-Chemical 0
alone O 0
induced O 0
significant O 0
cardiac B-Disease 0
damage I-Disease 0
in O 0
comparison O 0
to O 0
the O 0
saline O 0
control O 0
group O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

RESULTS O 0
: O 0
The O 0
number O 0
of O 0
damaged O 0
cardiomyocytes O 0
was O 0
9 O 0
. O 0
6 O 0
- O 0
fold O 0
( O 0
95 O 0
% O 0
CI O 0
4 O 0
. O 0
4 O 0
- O 0
21 O 0
. O 0
0 O 0
) O 0
higher O 0
in O 0
mice O 0
treated O 0
with O 0
DOX B-Chemical 0
alone O 0
than O 0
that O 0
in O 0
animals O 0
of O 0
the O 0
control O 0
group O 0
. O 0

The O 0
ratio O 0
of O 0
aberrant O 0
cardiomyocytes O 0
in O 0
mice O 0
treated O 0
with O 0
DOX B-Chemical 0
preceded O 0
by O 0
monoHER B-Chemical 0
and O 0
those O 0
in O 0
mice O 0
treated O 0
with O 0
saline O 0
ranged O 0
from O 0
1 O 0
. O 0
6 O 0
to O 0
2 O 0
. O 0
8 O 0
( O 0
mean O 0
2 O 0
. O 0
2 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
2 O 0
- O 0
4 O 0
. O 0
1 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
019 O 0
) O 0
. O 0

The O 0
mean O 0
protective O 0
effect O 0
by O 0
adding O 0
monoHER B-Chemical 0
before O 0
DOX B-Chemical 0
led O 0
to O 0
a O 0
significant O 0
4 O 0
. O 0
4 O 0
- O 0
fold O 0
reduction O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
, O 0
95 O 0
% O 0
CI O 0
2 O 0
. O 0
3 O 0
- O 0
8 O 0
. O 0
2 O 0
) O 0
of O 0
abnormal O 0
cardiomyocytes O 0
. O 0

This O 0
protective O 0
effect O 0
did O 0
not O 0
depend O 0
on O 0
the O 0
time O 0
interval O 0
between O 0
monoHER B-Chemical 0
and O 0
DOX B-Chemical 0
administration O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
345 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
results O 0
indicate O 0
that O 0
in O 0
an O 0
outpatient O 0
clinical O 0
setting O 0
monoHER B-Chemical 0
may O 0
be O 0
administered O 0
shortly O 0
before O 0
DOX B-Chemical 0
. O 0

Clinical O 0
evaluation O 0
of O 0
adverse O 0
effects O 0
during O 0
bepridil B-Chemical 0
administration O 0
for O 0
atrial B-Disease 0
fibrillation I-Disease 0
and I-Disease 0
flutter I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Bepridil B-Chemical 0
hydrochloride I-Chemical 0
( O 0
Bpd B-Chemical 0
) O 0
has O 0
attracted O 0
attention O 0
as O 0
an O 0
effective O 0
drug O 0
for O 0
atrial B-Disease 0
fibrillation I-Disease 0
( O 0
AF B-Disease 0
) O 0
and O 0
atrial B-Disease 0
flutter I-Disease 0
( O 0
AFL B-Disease 0
) O 0
. O 0

However O 0
, O 0
serious O 0
adverse O 0
effects O 0
, O 0
including O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
( O 0
Tdp B-Disease 0
) O 0
, O 0
have O 0
been O 0
reported O 0
. O 0

METHODS O 0
AND O 0
RESULTS O 0
: O 0
Adverse O 0
effects O 0
of O 0
Bpd B-Chemical 0
requiring O 0
discontinuation O 0
of O 0
treatment O 0
were O 0
evaluated O 0
. O 0

Bpd B-Chemical 0
was O 0
administered O 0
to O 0
459 O 0
patients O 0
( O 0
361 O 0
males O 0
, O 0
63 O 0
+ O 0
/ O 0
- O 0
12 O 0
years O 0
old O 0
) O 0
comprising O 0
378 O 0
AF B-Disease 0
and O 0
81 O 0
AFL B-Disease 0
cases O 0
. O 0

Mean O 0
left O 0
ventricular O 0
ejection O 0
fraction O 0
and O 0
atrial O 0
dimension O 0
( O 0
LAD O 0
) O 0
were O 0
66 O 0
+ O 0
/ O 0
- O 0
11 O 0
% O 0
and O 0
40 O 0
+ O 0
/ O 0
- O 0
6 O 0
mm O 0
, O 0
respectively O 0
. O 0

Adverse O 0
effects O 0
were O 0
observed O 0
in O 0
19 O 0
patients O 0
( O 0
4 O 0
% O 0
) O 0
during O 0
an O 0
average O 0
follow O 0
- O 0
up O 0
of O 0
20 O 0
months O 0
. O 0

There O 0
was O 0
marked O 0
QT B-Disease 0
prolongation I-Disease 0
greater O 0
than O 0
0 O 0
. O 0
55 O 0
s O 0
in O 0
13 O 0
patients O 0
, O 0
bradycardia B-Disease 0
less O 0
than O 0
40 O 0
beats O 0
/ O 0
min O 0
in O 0
6 O 0
patients O 0
, O 0
dizziness B-Disease 0
and O 0
general O 0
fatigue B-Disease 0
in O 0
1 O 0
patient O 0
each O 0
. O 0

In O 0
4 O 0
of O 0
13 O 0
patients O 0
with O 0
QT B-Disease 0
prolongation I-Disease 0
, O 0
Tdp B-Disease 0
occurred O 0
. O 0

The O 0
major O 0
triggering O 0
factors O 0
of O 0
Tdp B-Disease 0
were O 0
hypokalemia B-Disease 0
and O 0
sudden O 0
decrease O 0
in O 0
heart O 0
rate O 0
. O 0

There O 0
were O 0
no O 0
differences O 0
in O 0
the O 0
clinical O 0
backgrounds O 0
of O 0
the O 0
patients O 0
with O 0
and O 0
without O 0
Tdp B-Disease 0
other O 0
than O 0
LAD O 0
and O 0
age O 0
, O 0
which O 0
were O 0
larger O 0
and O 0
older O 0
in O 0
the O 0
patients O 0
with O 0
Tdp B-Disease 0
. O 0

CONCLUSION O 0
: O 0
Careful O 0
observation O 0
of O 0
serum O 0
potassium B-Chemical 0
concentration O 0
and O 0
the O 0
ECG O 0
should O 0
always O 0
be O 0
done O 0
during O 0
Bpd B-Chemical 0
administration O 0
, O 0
particularly O 0
in O 0
elderly O 0
patients O 0
. O 0

Enhanced O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
hypertrophy I-Disease 0
in O 0
transgenic O 0
rats O 0
with O 0
low O 0
brain O 0
angiotensinogen O 0
. O 0

We O 0
have O 0
previously O 0
shown O 0
that O 0
a O 0
permanent O 0
deficiency O 0
in O 0
the O 0
brain O 0
renin O 0
- O 0
angiotensin B-Chemical 0
system O 0
( O 0
RAS O 0
) O 0
may O 0
increase O 0
the O 0
sensitivity O 0
of O 0
the O 0
baroreflex O 0
control O 0
of O 0
heart O 0
rate O 0
. O 0

In O 0
this O 0
study O 0
we O 0
aimed O 0
at O 0
studying O 0
the O 0
involvement O 0
of O 0
the O 0
brain O 0
RAS O 0
in O 0
the O 0
cardiac O 0
reactivity O 0
to O 0
the O 0
beta O 0
- O 0
adrenoceptor O 0
( O 0
beta O 0
- O 0
AR O 0
) O 0
agonist O 0
isoproterenol B-Chemical 0
( O 0
Iso B-Chemical 0
) O 0
. O 0

Transgenic O 0
rats O 0
with O 0
low O 0
brain O 0
angiotensinogen O 0
( O 0
TGR O 0
) O 0
were O 0
used O 0
. O 0

In O 0
isolated O 0
hearts O 0
, O 0
Iso B-Chemical 0
induced O 0
a O 0
significantly O 0
greater O 0
increase O 0
in O 0
left O 0
ventricular O 0
( O 0
LV O 0
) O 0
pressure O 0
and O 0
maximal O 0
contraction O 0
( O 0
+ O 0
dP O 0
/ O 0
dt O 0
( O 0
max O 0
) O 0
) O 0
in O 0
the O 0
TGR O 0
than O 0
in O 0
the O 0
Sprague O 0
- O 0
Dawley O 0
( O 0
SD O 0
) O 0
rats O 0
. O 0

LV B-Disease 0
hypertrophy I-Disease 0
induced O 0
by O 0
Iso B-Chemical 0
treatment O 0
was O 0
significantly O 0
higher O 0
in O 0
TGR O 0
than O 0
in O 0
SD O 0
rats O 0
( O 0
in O 0
g O 0
LV O 0
wt O 0
/ O 0
100 O 0
g O 0
body O 0
wt O 0
, O 0
0 O 0
. O 0
28 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
004 O 0
vs O 0
. O 0
0 O 0
. O 0
24 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
004 O 0
, O 0
respectively O 0
) O 0
. O 0

The O 0
greater O 0
LV B-Disease 0
hypertrophy I-Disease 0
in O 0
TGR O 0
rats O 0
was O 0
associated O 0
with O 0
more O 0
pronounced O 0
downregulation O 0
of O 0
beta O 0
- O 0
AR O 0
and O 0
upregulation O 0
of O 0
LV O 0
beta O 0
- O 0
AR O 0
kinase O 0
- O 0
1 O 0
mRNA O 0
levels O 0
compared O 0
with O 0
those O 0
in O 0
SD O 0
rats O 0
. O 0

The O 0
decrease O 0
in O 0
the O 0
heart O 0
rate O 0
( O 0
HR O 0
) O 0
induced O 0
by O 0
the O 0
beta O 0
- O 0
AR O 0
antagonist O 0
metoprolol B-Chemical 0
in O 0
conscious O 0
rats O 0
was O 0
significantly O 0
attenuated O 0
in O 0
TGR O 0
compared O 0
with O 0
SD O 0
rats O 0
( O 0
- O 0
9 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
7 O 0
% O 0
vs O 0
. O 0
- O 0
18 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
5 O 0
% O 0
) O 0
, O 0
whereas O 0
the O 0
effect O 0
of O 0
parasympathetic O 0
blockade O 0
by O 0
atropine B-Chemical 0
on O 0
HR O 0
was O 0
similar O 0
in O 0
both O 0
strains O 0
. O 0

These O 0
results O 0
indicate O 0
that O 0
TGR O 0
are O 0
more O 0
sensitive O 0
to O 0
beta O 0
- O 0
AR O 0
agonist O 0
- O 0
induced O 0
cardiac B-Disease 0
inotropic I-Disease 0
response O 0
and O 0
hypertrophy B-Disease 0
, O 0
possibly O 0
due O 0
to O 0
chronically O 0
low O 0
sympathetic O 0
outflow O 0
directed O 0
to O 0
the O 0
heart O 0
. O 0

Drug O 0
- O 0
induced O 0
long B-Disease 0
QT I-Disease 0
syndrome I-Disease 0
in O 0
injection O 0
drug O 0
users O 0
receiving O 0
methadone B-Chemical 0
: O 0
high O 0
frequency O 0
in O 0
hospitalized O 0
patients O 0
and O 0
risk O 0
factors O 0
. O 0

BACKGROUND O 0
: O 0
Drug O 0
- O 0
induced O 0
long B-Disease 0
QT I-Disease 0
syndrome I-Disease 0
is O 0
a O 0
serious O 0
adverse O 0
drug O 0
reaction O 0
. O 0

Methadone B-Chemical 0
prolongs O 0
the O 0
QT O 0
interval O 0
in O 0
vitro O 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
manner O 0
. O 0

In O 0
the O 0
inpatient O 0
setting O 0
, O 0
the O 0
frequency O 0
of O 0
QT B-Disease 0
interval I-Disease 0
prolongation I-Disease 0
with O 0
methadone B-Chemical 0
treatment O 0
, O 0
its O 0
dose O 0
dependence O 0
, O 0
and O 0
the O 0
importance O 0
of O 0
cofactors O 0
such O 0
as O 0
drug O 0
- O 0
drug O 0
interactions O 0
remain O 0
unknown O 0
. O 0

METHODS O 0
: O 0
We O 0
performed O 0
a O 0
systematic O 0
, O 0
retrospective O 0
study O 0
comparing O 0
active O 0
or O 0
former O 0
intravenous O 0
drug O 0
users O 0
receiving O 0
methadone B-Chemical 0
and O 0
those O 0
not O 0
receiving O 0
methadone B-Chemical 0
among O 0
all O 0
patients O 0
hospitalized O 0
over O 0
a O 0
5 O 0
- O 0
year O 0
period O 0
in O 0
a O 0
tertiary O 0
care O 0
hospital O 0
. O 0

A O 0
total O 0
of O 0
167 O 0
patients O 0
receiving O 0
methadone B-Chemical 0
fulfilled O 0
the O 0
inclusion O 0
criteria O 0
and O 0
were O 0
compared O 0
with O 0
a O 0
control O 0
group O 0
of O 0
80 O 0
injection O 0
drug O 0
users O 0
not O 0
receiving O 0
methadone B-Chemical 0
. O 0

In O 0
addition O 0
to O 0
methadone B-Chemical 0
dose O 0
, O 0
15 O 0
demographic O 0
, O 0
biological O 0
, O 0
and O 0
pharmacological O 0
variables O 0
were O 0
considered O 0
as O 0
potential O 0
risk O 0
factors O 0
for O 0
QT B-Disease 0
prolongation I-Disease 0
. O 0

RESULTS O 0
: O 0
Among O 0
167 O 0
methadone B-Chemical 0
maintenance O 0
patients O 0
, O 0
the O 0
prevalence O 0
of O 0
QTc O 0
prolongation O 0
to O 0
0 O 0
. O 0
50 O 0
second O 0
( O 0
( O 0
1 O 0
/ O 0
2 O 0
) O 0
) O 0
or O 0
longer O 0
was O 0
16 O 0
. O 0
2 O 0
% O 0
compared O 0
with O 0
0 O 0
% O 0
in O 0
80 O 0
control O 0
subjects O 0
. O 0

Six O 0
patients O 0
( O 0
3 O 0
. O 0
6 O 0
% O 0
) O 0
in O 0
the O 0
methadone B-Chemical 0
group O 0
presented O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
. O 0

QTc O 0
length O 0
was O 0
weakly O 0
but O 0
significantly O 0
associated O 0
with O 0
methadone B-Chemical 0
daily O 0
dose O 0
( O 0
Spearman O 0
rank O 0
correlation O 0
coefficient O 0
, O 0
0 O 0
. O 0
20 O 0
; O 0
P O 0
< O 0
. O 0
01 O 0
) O 0
. O 0

Multivariate O 0
regression O 0
analysis O 0
allowed O 0
attribution O 0
of O 0
31 O 0
. O 0
8 O 0
% O 0
of O 0
QTc O 0
variability O 0
to O 0
methadone B-Chemical 0
dose O 0
, O 0
cytochrome O 0
P O 0
- O 0
450 O 0
3A4 O 0
drug O 0
- O 0
drug O 0
interactions O 0
, O 0
hypokalemia B-Disease 0
, O 0
and O 0
altered O 0
liver O 0
function O 0
. O 0

CONCLUSIONS O 0
: O 0
QT B-Disease 0
interval I-Disease 0
prolongation I-Disease 0
in O 0
methadone B-Chemical 0
maintenance O 0
patients O 0
hospitalized O 0
in O 0
a O 0
tertiary O 0
care O 0
center O 0
is O 0
a O 0
frequent O 0
finding O 0
. O 0

Methadone B-Chemical 0
dose O 0
, O 0
presence O 0
of O 0
cytochrome O 0
P O 0
- O 0
450 O 0
3A4 O 0
inhibitors O 0
, O 0
potassium B-Chemical 0
level O 0
, O 0
and O 0
liver O 0
function O 0
contribute O 0
to O 0
QT B-Disease 0
prolongation I-Disease 0
. O 0

Long B-Disease 0
QT I-Disease 0
syndrome I-Disease 0
can O 0
occur O 0
with O 0
low O 0
doses O 0
of O 0
methadone B-Chemical 0
. O 0

Mechanisms O 0
of O 0
hypertension B-Disease 0
induced O 0
by O 0
nitric B-Chemical 0
oxide I-Chemical 0
( O 0
NO B-Chemical 0
) O 0
deficiency O 0
: O 0
focus O 0
on O 0
venous O 0
function O 0
. O 0

Loss O 0
of O 0
endothelial O 0
cell O 0
- O 0
derived O 0
nitric B-Chemical 0
oxide I-Chemical 0
( O 0
NO B-Chemical 0
) O 0
in O 0
hypertension B-Disease 0
is O 0
a O 0
hallmark O 0
of O 0
arterial B-Disease 0
dysfunction I-Disease 0
. O 0

Experimental O 0
hypertension B-Disease 0
created O 0
by O 0
the O 0
removal O 0
of O 0
NO B-Chemical 0
, O 0
however O 0
, O 0
involves O 0
mechanisms O 0
in O 0
addition O 0
to O 0
decreased O 0
arterial O 0
vasodilator O 0
activity O 0
. O 0

These O 0
include O 0
augmented O 0
endothelin O 0
- O 0
1 O 0
( O 0
ET O 0
- O 0
1 O 0
) O 0
release O 0
, O 0
increased O 0
sympathetic O 0
nervous O 0
system O 0
activity O 0
, O 0
and O 0
elevated O 0
tissue O 0
oxidative O 0
stress O 0
. O 0

We O 0
hypothesized O 0
that O 0
increased O 0
venous O 0
smooth O 0
muscle O 0
( O 0
venomotor O 0
) O 0
tone O 0
plays O 0
a O 0
role O 0
in O 0
Nomega B-Chemical 0
- I-Chemical 0
nitro I-Chemical 0
- I-Chemical 0
L I-Chemical 0
- I-Chemical 0
arginine I-Chemical 0
( O 0
LNNA B-Chemical 0
) O 0
hypertension B-Disease 0
through O 0
these O 0
mechanisms O 0
. O 0

Rats O 0
were O 0
treated O 0
with O 0
the O 0
NO B-Chemical 0
synthase O 0
inhibitor O 0
LNNA B-Chemical 0
( O 0
0 O 0
. O 0
5 O 0
g O 0
/ O 0
L O 0
in O 0
drinking O 0
water O 0
) O 0
for O 0
2 O 0
weeks O 0
. O 0

Mean O 0
arterial O 0
pressure O 0
of O 0
conscious O 0
rats O 0
was O 0
119 O 0
+ O 0
/ O 0
- O 0
2 O 0
mm O 0
Hg O 0
in O 0
control O 0
and O 0
194 O 0
+ O 0
/ O 0
- O 0
5 O 0
mm O 0
Hg O 0
in O 0
LNNA B-Chemical 0
rats O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Carotid O 0
arteries O 0
and O 0
vena O 0
cava O 0
were O 0
removed O 0
for O 0
measurement O 0
of O 0
isometric O 0
contraction O 0
. O 0

Maximal O 0
contraction O 0
to O 0
norepinephrine B-Chemical 0
was O 0
modestly O 0
reduced O 0
in O 0
arteries O 0
from O 0
LNNA B-Chemical 0
compared O 0
with O 0
control O 0
rats O 0
whereas O 0
the O 0
maximum O 0
contraction O 0
to O 0
ET O 0
- O 0
1 O 0
was O 0
significantly O 0
reduced O 0
( O 0
54 O 0
% O 0
control O 0
) O 0
. O 0

Maximum O 0
contraction O 0
of O 0
vena O 0
cava O 0
to O 0
norepinephrine B-Chemical 0
( O 0
37 O 0
% O 0
control O 0
) O 0
also O 0
was O 0
reduced O 0
but O 0
no O 0
change O 0
in O 0
response O 0
to O 0
ET O 0
- O 0
1 O 0
was O 0
observed O 0
. O 0

Mean O 0
circulatory O 0
filling O 0
pressure O 0
, O 0
an O 0
in O 0
vivo O 0
measure O 0
of O 0
venomotor O 0
tone O 0
, O 0
was O 0
not O 0
elevated O 0
in O 0
LNNA B-Chemical 0
hypertension B-Disease 0
at O 0
1 O 0
or O 0
2 O 0
weeks O 0
after O 0
LNNA B-Chemical 0
. O 0

The O 0
superoxide B-Chemical 0
scavenger O 0
tempol B-Chemical 0
( O 0
30 O 0
, O 0
100 O 0
, O 0
and O 0
300 O 0
micromol O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
, O 0
IV O 0
) O 0
did O 0
not O 0
change O 0
arterial O 0
pressure O 0
in O 0
control O 0
rats O 0
but O 0
caused O 0
a O 0
dose O 0
- O 0
dependent O 0
decrease O 0
in O 0
LNNA B-Chemical 0
rats O 0
( O 0
- O 0
18 O 0
+ O 0
/ O 0
- O 0
8 O 0
, O 0
- O 0
26 O 0
+ O 0
/ O 0
- O 0
15 O 0
, O 0
and O 0
- O 0
54 O 0
+ O 0
/ O 0
- O 0
11 O 0
mm O 0
Hg O 0
) O 0
. O 0

Similarly O 0
, O 0
ganglionic O 0
blockade O 0
with O 0
hexamethonium B-Chemical 0
caused O 0
a O 0
significantly O 0
greater O 0
fall O 0
in O 0
LNNA B-Chemical 0
hypertensive B-Disease 0
rats O 0
( O 0
76 O 0
+ O 0
/ O 0
- O 0
9 O 0
mm O 0
Hg O 0
) O 0
compared O 0
with O 0
control O 0
rats O 0
( O 0
35 O 0
+ O 0
/ O 0
- O 0
10 O 0
mm O 0
Hg O 0
) O 0
. O 0

Carotid O 0
arteries O 0
, O 0
vena O 0
cava O 0
, O 0
and O 0
sympathetic O 0
ganglia O 0
from O 0
LNNA B-Chemical 0
rats O 0
had O 0
higher O 0
basal O 0
levels O 0
of O 0
superoxide B-Chemical 0
compared O 0
with O 0
those O 0
from O 0
control O 0
rats O 0
. O 0

These O 0
data O 0
suggest O 0
that O 0
while O 0
NO B-Chemical 0
deficiency O 0
increases O 0
oxidative O 0
stress O 0
and O 0
sympathetic O 0
activity O 0
in O 0
both O 0
arterial O 0
and O 0
venous O 0
vessels O 0
, O 0
the O 0
impact O 0
on O 0
veins O 0
does O 0
not O 0
make O 0
a O 0
major O 0
contribution O 0
to O 0
this O 0
form O 0
of O 0
hypertension B-Disease 0
. O 0

Association O 0
of O 0
DRD2 O 0
polymorphisms O 0
and O 0
chlorpromazine B-Chemical 0
- O 0
induced O 0
extrapyramidal B-Disease 0
syndrome I-Disease 0
in O 0
Chinese O 0
schizophrenic B-Disease 0
patients O 0
. O 0

AIM O 0
: O 0
Extrapyramidal B-Disease 0
syndrome I-Disease 0
( O 0
EPS B-Disease 0
) O 0
is O 0
most O 0
commonly O 0
affected O 0
by O 0
typical O 0
antipsychotic O 0
drugs O 0
that O 0
have O 0
a O 0
high O 0
affinity O 0
with O 0
the O 0
D2 O 0
receptor O 0
. O 0

Recently O 0
, O 0
many O 0
research O 0
groups O 0
have O 0
reported O 0
on O 0
the O 0
positive O 0
relationship O 0
between O 0
the O 0
genetic O 0
variations O 0
in O 0
the O 0
DRD2 O 0
gene O 0
and O 0
the O 0
therapeutic O 0
response O 0
in O 0
schizophrenia B-Disease 0
patients O 0
as O 0
a O 0
result O 0
of O 0
the O 0
role O 0
of O 0
variations O 0
in O 0
the O 0
receptor O 0
in O 0
modulating O 0
receptor O 0
expression O 0
. O 0

In O 0
this O 0
study O 0
, O 0
we O 0
evaluate O 0
the O 0
role O 0
DRD2 O 0
plays O 0
in O 0
chlorpromazine B-Chemical 0
- O 0
induced O 0
EPS B-Disease 0
in O 0
schizophrenic B-Disease 0
patients O 0
. O 0

METHODS O 0
: O 0
We O 0
identified O 0
seven O 0
SNP O 0
( O 0
single O 0
nucleotide O 0
polymorphism O 0
) O 0
( O 0
- O 0
141Cins O 0
> O 0
del O 0
, O 0
TaqIB O 0
, O 0
TaqID O 0
, O 0
Ser311Cys O 0
, O 0
rs6275 O 0
, O 0
rs6277 O 0
and O 0
TaqIA O 0
) O 0
in O 0
the O 0
DRD2 O 0
gene O 0
in O 0
146 O 0
schizophrenic B-Disease 0
inpatients O 0
( O 0
59 O 0
with O 0
EPS B-Disease 0
and O 0
87 O 0
without O 0
EPS B-Disease 0
according O 0
to O 0
the O 0
Simpson O 0
- O 0
Angus O 0
Scale O 0
) O 0
treated O 0
with O 0
chlorpromazine B-Chemical 0
after O 0
8 O 0
weeks O 0
. O 0

The O 0
alleles O 0
of O 0
all O 0
loci O 0
were O 0
determined O 0
by O 0
PCR O 0
( O 0
polymerase O 0
chain O 0
reaction O 0
) O 0
. O 0

RESULTS O 0
: O 0
Polymorphisms O 0
TaqID O 0
, O 0
Ser311Cys O 0
and O 0
rs6277 O 0
were O 0
not O 0
polymorphic O 0
in O 0
the O 0
population O 0
recruited O 0
in O 0
the O 0
present O 0
study O 0
. O 0

No O 0
statistical O 0
significance O 0
was O 0
found O 0
in O 0
the O 0
allele O 0
distribution O 0
of O 0
- O 0
141Cins O 0
> O 0
del O 0
, O 0
TaqIB O 0
, O 0
rs6275 O 0
and O 0
TaqIA O 0
or O 0
in O 0
the O 0
estimated O 0
haplotypes O 0
( O 0
constituted O 0
by O 0
TaqIB O 0
, O 0
rs6275 O 0
and O 0
TaqIA O 0
) O 0
in O 0
linkage O 0
disequilibrium O 0
between O 0
the O 0
two O 0
groups O 0
. O 0

CONCLUSION O 0
: O 0
Our O 0
results O 0
did O 0
not O 0
lend O 0
strong O 0
support O 0
to O 0
the O 0
view O 0
that O 0
the O 0
genetic O 0
variation O 0
of O 0
the O 0
DRD2 O 0
gene O 0
plays O 0
a O 0
major O 0
role O 0
in O 0
the O 0
individually O 0
variable O 0
adverse O 0
effect O 0
induced O 0
by O 0
chlorpromazine B-Chemical 0
, O 0
at O 0
least O 0
in O 0
Chinese O 0
patients O 0
with O 0
schizophrenia B-Disease 0
. O 0

Our O 0
results O 0
confirmed O 0
a O 0
previous O 0
study O 0
on O 0
the O 0
relationship O 0
between O 0
DRD2 O 0
and O 0
EPS B-Disease 0
in O 0
Caucasians O 0
. O 0

Physical O 0
training O 0
decreases O 0
susceptibility O 0
to O 0
subsequent O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
in O 0
the O 0
rat O 0
. O 0

Regular O 0
motor O 0
activity O 0
has O 0
many O 0
benefits O 0
for O 0
mental O 0
and O 0
physical O 0
condition O 0
but O 0
its O 0
implications O 0
for O 0
epilepsy B-Disease 0
are O 0
still O 0
controversial O 0
. O 0

In O 0
order O 0
to O 0
elucidate O 0
this O 0
problem O 0
, O 0
we O 0
have O 0
studied O 0
the O 0
effect O 0
of O 0
long O 0
- O 0
term O 0
physical O 0
activity O 0
on O 0
susceptibility O 0
to O 0
subsequent O 0
seizures B-Disease 0
. O 0

Male O 0
Wistar O 0
rats O 0
were O 0
subjected O 0
to O 0
repeated O 0
training O 0
sessions O 0
in O 0
a O 0
treadmill O 0
and O 0
swimming O 0
pool O 0
. O 0

Thereafter O 0
, O 0
seizures B-Disease 0
were O 0
induced O 0
by O 0
pilocarpine B-Chemical 0
injections O 0
in O 0
trained O 0
and O 0
non O 0
- O 0
trained O 0
control O 0
groups O 0
. O 0

During O 0
the O 0
acute O 0
period O 0
of O 0
status B-Disease 0
epilepticus I-Disease 0
, O 0
we O 0
measured O 0
: O 0
( O 0
1 O 0
) O 0
the O 0
latency O 0
of O 0
the O 0
first O 0
motor O 0
sign O 0
, O 0
( O 0
2 O 0
) O 0
the O 0
intensity O 0
of O 0
seizures B-Disease 0
, O 0
( O 0
3 O 0
) O 0
the O 0
time O 0
when O 0
it O 0
occurred O 0
within O 0
the O 0
6 O 0
- O 0
h O 0
observation O 0
period O 0
, O 0
and O 0
( O 0
4 O 0
) O 0
the O 0
time O 0
when O 0
the O 0
acute O 0
period O 0
ended O 0
. O 0

All O 0
these O 0
behavioral O 0
parameters O 0
showed O 0
statistically O 0
significant O 0
changes O 0
suggesting O 0
that O 0
regular O 0
physical O 0
exercises O 0
decrease O 0
susceptibility O 0
to O 0
subsequently O 0
induced O 0
seizures B-Disease 0
and O 0
ameliorate O 0
the O 0
course O 0
of O 0
experimentally O 0
induced O 0
status B-Disease 0
epilepticus I-Disease 0
. O 0

Tonic O 0
dopaminergic O 0
stimulation O 0
impairs B-Disease 0
associative I-Disease 0
learning I-Disease 0
in O 0
healthy O 0
subjects O 0
. O 0

Endogenous O 0
dopamine B-Chemical 0
plays O 0
a O 0
central O 0
role O 0
in O 0
salience O 0
coding O 0
during O 0
associative O 0
learning O 0
. O 0

Administration O 0
of O 0
the O 0
dopamine B-Chemical 0
precursor O 0
levodopa B-Chemical 0
enhances O 0
learning O 0
in O 0
healthy O 0
subjects O 0
and O 0
stroke B-Disease 0
patients O 0
. O 0

Because O 0
levodopa B-Chemical 0
increases O 0
both O 0
phasic O 0
and O 0
tonic O 0
dopaminergic O 0
neurotransmission O 0
, O 0
the O 0
critical O 0
mechanism O 0
mediating O 0
the O 0
enhancement O 0
of O 0
learning O 0
is O 0
unresolved O 0
. O 0

We O 0
here O 0
probed O 0
how O 0
selective O 0
tonic O 0
dopaminergic O 0
stimulation O 0
affects O 0
associative O 0
learning O 0
. O 0

Forty O 0
healthy O 0
subjects O 0
were O 0
trained O 0
in O 0
a O 0
novel O 0
vocabulary O 0
of O 0
45 O 0
concrete O 0
nouns O 0
over O 0
the O 0
course O 0
of O 0
5 O 0
consecutive O 0
training O 0
days O 0
in O 0
a O 0
prospective O 0
, O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
placebo O 0
- O 0
controlled O 0
design O 0
. O 0

Subjects O 0
received O 0
the O 0
tonically O 0
stimulating O 0
dopamine B-Chemical 0
- O 0
receptor O 0
agonist O 0
pergolide B-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
mg O 0
) O 0
vs O 0
placebo O 0
120 O 0
min O 0
before O 0
training O 0
on O 0
each O 0
training O 0
day O 0
. O 0

The O 0
dopamine B-Chemical 0
agonist O 0
significantly O 0
impaired B-Disease 0
novel I-Disease 0
word I-Disease 0
learning I-Disease 0
compared O 0
to O 0
placebo O 0
. O 0

This O 0
learning O 0
decrement O 0
persisted O 0
up O 0
to O 0
the O 0
last O 0
follow O 0
- O 0
up O 0
4 O 0
weeks O 0
post O 0
- O 0
training O 0
. O 0

Subjects O 0
treated O 0
with O 0
pergolide B-Chemical 0
also O 0
showed O 0
restricted O 0
emotional O 0
responses O 0
compared O 0
to O 0
the O 0
PLACEBO O 0
group O 0
. O 0

The O 0
extent O 0
of O 0
' O 0
flattened O 0
' O 0
affect O 0
with O 0
pergolide B-Chemical 0
was O 0
related O 0
to O 0
the O 0
degree O 0
of O 0
learning O 0
inhibition O 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
tonic O 0
occupation O 0
of O 0
dopamine B-Chemical 0
receptors O 0
impairs O 0
learning O 0
by O 0
competition O 0
with O 0
phasic O 0
dopamine B-Chemical 0
signals O 0
. O 0

Thus O 0
, O 0
phasic O 0
signaling O 0
seems O 0
to O 0
be O 0
the O 0
critical O 0
mechanism O 0
by O 0
which O 0
dopamine B-Chemical 0
enhances O 0
associative O 0
learning O 0
in O 0
healthy O 0
subjects O 0
and O 0
stroke B-Disease 0
patients O 0
. O 0

Minocycline B-Chemical 0
- O 0
induced O 0
vasculitis B-Disease 0
fulfilling O 0
the O 0
criteria O 0
of O 0
polyarteritis B-Disease 0
nodosa I-Disease 0
. O 0

A O 0
47 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
who O 0
had O 0
been O 0
taking O 0
minocycline B-Chemical 0
for O 0
palmoplantar B-Disease 0
pustulosis I-Disease 0
developed O 0
fever B-Disease 0
, O 0
myalgias B-Disease 0
, O 0
polyneuropathy B-Disease 0
, O 0
and O 0
testicular B-Disease 0
pain I-Disease 0
, O 0
with O 0
elevated O 0
C O 0
- O 0
reactive O 0
protein O 0
( O 0
CRP O 0
) O 0
. O 0

Neither O 0
myeloperoxidase O 0
- O 0
nor O 0
proteinase O 0
- O 0
3 O 0
- O 0
antineutrophil O 0
cytoplasmic O 0
antibody O 0
was O 0
positive O 0
. O 0

These O 0
manifestations O 0
met O 0
the O 0
American O 0
College O 0
of O 0
Rheumatology O 0
1990 O 0
criteria O 0
for O 0
the O 0
classification O 0
of O 0
polyarteritis B-Disease 0
nodosa I-Disease 0
. O 0

Stopping O 0
minocycline B-Chemical 0
led O 0
to O 0
amelioration O 0
of O 0
symptoms O 0
and O 0
normalization O 0
of O 0
CRP O 0
level O 0
. O 0

To O 0
our O 0
knowledge O 0
, O 0
this O 0
is O 0
the O 0
second O 0
case O 0
of O 0
minocycline B-Chemical 0
- O 0
induced O 0
vasculitis B-Disease 0
satisfying O 0
the O 0
criteria O 0
. O 0

Differential O 0
diagnosis O 0
for O 0
drug O 0
- O 0
induced O 0
disease O 0
is O 0
invaluable O 0
even O 0
for O 0
patients O 0
with O 0
classical O 0
polyarteritis B-Disease 0
nodosa I-Disease 0
. O 0

Intramuscular O 0
hepatitis B-Disease 0
B I-Disease 0
immune O 0
globulin O 0
combined O 0
with O 0
lamivudine B-Chemical 0
in O 0
prevention O 0
of O 0
hepatitis B-Disease 0
B I-Disease 0
recurrence O 0
after O 0
liver O 0
transplantation O 0
. O 0

BACKGROUND O 0
: O 0
Combined O 0
hepatitis B-Disease 0
B I-Disease 0
immune O 0
globulin O 0
( O 0
HBIg O 0
) O 0
and O 0
lamivudine B-Chemical 0
in O 0
prophylaxis O 0
of O 0
the O 0
recurrence O 0
of O 0
hepatitis B-Disease 0
B I-Disease 0
after O 0
liver O 0
transplantation O 0
has O 0
significantly O 0
improved O 0
the O 0
survival O 0
of O 0
HBsAg B-Chemical 0
positive O 0
patients O 0
. O 0

This O 0
study O 0
was O 0
undertaken O 0
to O 0
evaluate O 0
the O 0
outcomes O 0
of O 0
liver O 0
transplantation O 0
for O 0
patients O 0
with O 0
hepatitis B-Disease 0
B I-Disease 0
virus O 0
( O 0
HBV O 0
) O 0
. O 0

METHODS O 0
: O 0
A O 0
retrospective O 0
chart O 0
analysis O 0
and O 0
a O 0
review O 0
of O 0
the O 0
organ O 0
transplant O 0
database O 0
identified O 0
51 O 0
patients O 0
( O 0
43 O 0
men O 0
and O 0
8 O 0
women O 0
) O 0
transplanted O 0
for O 0
benign O 0
HBV O 0
- O 0
related O 0
cirrhotic B-Disease 0
diseases I-Disease 0
between O 0
June O 0
2002 O 0
and O 0
December O 0
2004 O 0
who O 0
had O 0
survived O 0
more O 0
than O 0
3 O 0
months O 0
. O 0

HBIg O 0
was O 0
administered O 0
intravenously O 0
during O 0
the O 0
first O 0
week O 0
and O 0
intramuscularly O 0
thereafter O 0
. O 0

RESULTS O 0
: O 0
At O 0
a O 0
median O 0
follow O 0
- O 0
up O 0
of O 0
14 O 0
. O 0
1 O 0
months O 0
, O 0
the O 0
overall O 0
recurrence O 0
rate O 0
in O 0
the O 0
51 O 0
patients O 0
was O 0
3 O 0
. O 0
9 O 0
% O 0
( O 0
2 O 0
/ O 0
51 O 0
) O 0
. O 0

The O 0
overall O 0
patient O 0
survival O 0
was O 0
88 O 0
. O 0
3 O 0
% O 0
, O 0
and O 0
82 O 0
. O 0
4 O 0
% O 0
after O 0
1 O 0
and O 0
2 O 0
years O 0
, O 0
respectively O 0
. O 0

A O 0
daily O 0
oral O 0
dose O 0
of O 0
100 O 0
mg O 0
lamivudine B-Chemical 0
for O 0
2 O 0
weeks O 0
before O 0
transplantation O 0
for O 0
10 O 0
patients O 0
enabled O 0
57 O 0
. O 0
1 O 0
% O 0
( O 0
4 O 0
/ O 0
7 O 0
) O 0
and O 0
62 O 0
. O 0
5 O 0
% O 0
( O 0
5 O 0
/ O 0
8 O 0
) O 0
of O 0
HBV O 0
- O 0
DNA O 0
and O 0
HBeAg B-Chemical 0
positive O 0
patients O 0
respectively O 0
to O 0
convert O 0
to O 0
be O 0
negative O 0
. O 0

Intramuscular O 0
HBIg O 0
was O 0
well O 0
tolerated O 0
in O 0
all O 0
patients O 0
. O 0

CONCLUSION O 0
: O 0
Lamivudine B-Chemical 0
combined O 0
with O 0
intramuscular O 0
HBIg O 0
can O 0
effectively O 0
prevent O 0
allograft O 0
from O 0
the O 0
recurrence O 0
of O 0
HBV O 0
after O 0
liver O 0
transplantation O 0
. O 0

Anticonvulsant O 0
effect O 0
of O 0
eslicarbazepine B-Chemical 0
acetate I-Chemical 0
( O 0
BIA B-Chemical 0
2 I-Chemical 0
- I-Chemical 0
093 I-Chemical 0
) O 0
on O 0
seizures B-Disease 0
induced O 0
by O 0
microperfusion O 0
of O 0
picrotoxin B-Chemical 0
in O 0
the O 0
hippocampus O 0
of O 0
freely O 0
moving O 0
rats O 0
. O 0

Eslicarbazepine B-Chemical 0
acetate I-Chemical 0
( O 0
BIA B-Chemical 0
2 I-Chemical 0
- I-Chemical 0
093 I-Chemical 0
, O 0
S B-Chemical 0
- I-Chemical 0
( I-Chemical 0
- I-Chemical 0
) I-Chemical 0
- I-Chemical 0
10 I-Chemical 0
- I-Chemical 0
acetoxy I-Chemical 0
- I-Chemical 0
10 I-Chemical 0
, I-Chemical 0
11 I-Chemical 0
- I-Chemical 0
dihydro I-Chemical 0
- I-Chemical 0
5H I-Chemical 0
- I-Chemical 0
dibenzo I-Chemical 0
/ I-Chemical 0
b I-Chemical 0
, I-Chemical 0
f I-Chemical 0
/ I-Chemical 0
azepine I-Chemical 0
- I-Chemical 0
5 I-Chemical 0
- I-Chemical 0
carboxamide I-Chemical 0
) O 0
is O 0
a O 0
novel O 0
antiepileptic O 0
drug O 0
, O 0
now O 0
in O 0
Phase O 0
III O 0
clinical O 0
trials O 0
, O 0
designed O 0
with O 0
the O 0
aim O 0
of O 0
improving O 0
efficacy O 0
and O 0
safety O 0
in O 0
comparison O 0
with O 0
the O 0
structurally O 0
related O 0
drugs O 0
carbamazepine B-Chemical 0
( O 0
CBZ B-Chemical 0
) O 0
and O 0
oxcarbazepine B-Chemical 0
( O 0
OXC B-Chemical 0
) O 0
. O 0

We O 0
have O 0
studied O 0
the O 0
effects O 0
of O 0
oral O 0
treatment O 0
with O 0
eslicarbazepine B-Chemical 0
acetate I-Chemical 0
on O 0
a O 0
whole O 0
- O 0
animal O 0
model O 0
in O 0
which O 0
partial O 0
seizures B-Disease 0
can O 0
be O 0
elicited O 0
repeatedly O 0
on O 0
different O 0
days O 0
without O 0
changes O 0
in O 0
threshold O 0
or O 0
seizure B-Disease 0
patterns O 0
. O 0

In O 0
the O 0
animals O 0
treated O 0
with O 0
threshold O 0
doses O 0
of O 0
picrotoxin B-Chemical 0
, O 0
the O 0
average O 0
number O 0
of O 0
seizures B-Disease 0
was O 0
2 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
2 O 0
, O 0
and O 0
average O 0
seizure B-Disease 0
duration O 0
was O 0
39 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
8 O 0
. O 0
4s O 0
. O 0

Pre O 0
- O 0
treatment O 0
with O 0
a O 0
dose O 0
of O 0
30 O 0
mg O 0
/ O 0
kg O 0
2h O 0
before O 0
picrotoxin B-Chemical 0
microperfusion O 0
prevented O 0
seizures B-Disease 0
in O 0
the O 0
75 O 0
% O 0
of O 0
the O 0
rats O 0
. O 0

Lower O 0
doses O 0
( O 0
3 O 0
and O 0
10mg O 0
/ O 0
kg O 0
) O 0
did O 0
not O 0
suppress O 0
seizures B-Disease 0
, O 0
however O 0
, O 0
after O 0
administration O 0
of O 0
10mg O 0
/ O 0
kg O 0
, O 0
significant O 0
reductions O 0
in O 0
seizures B-Disease 0
duration O 0
( O 0
24 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
6 O 0
. O 0
8s O 0
) O 0
and O 0
seizure B-Disease 0
number O 0
( O 0
1 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
34 O 0
) O 0
were O 0
found O 0
. O 0

No O 0
adverse O 0
effects O 0
of O 0
eslicarbazepine B-Chemical 0
acetate I-Chemical 0
were O 0
observed O 0
in O 0
the O 0
behavioral O 0
/ O 0
EEG O 0
patterns O 0
studied O 0
, O 0
including O 0
sleep O 0
/ O 0
wakefulness O 0
cycle O 0
, O 0
at O 0
the O 0
doses O 0
studied O 0
. O 0

Acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
associated O 0
with O 0
prolonged O 0
intake O 0
of O 0
slimming O 0
pills O 0
containing O 0
anthraquinones B-Chemical 0
. O 0

Chinese B-Chemical 0
herbal I-Chemical 0
medicine O 0
preparations O 0
are O 0
widely O 0
available O 0
and O 0
often O 0
regarded O 0
by O 0
the O 0
public O 0
as O 0
natural O 0
and O 0
safe O 0
remedies O 0
for O 0
a O 0
variety O 0
of O 0
medical O 0
conditions O 0
. O 0

Nephropathy B-Disease 0
caused O 0
by O 0
Chinese B-Chemical 0
herbs I-Chemical 0
has O 0
previously O 0
been O 0
reported O 0
, O 0
usually O 0
involving O 0
the O 0
use O 0
of O 0
aristolochic B-Chemical 0
acids I-Chemical 0
. O 0

We O 0
report O 0
a O 0
23 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
who O 0
developed O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
following O 0
prolonged O 0
use O 0
of O 0
a O 0
proprietary O 0
Chinese B-Chemical 0
herbal I-Chemical 0
slimming O 0
pill O 0
that O 0
contained O 0
anthraquinone B-Chemical 0
derivatives O 0
, O 0
extracted O 0
from O 0
Rhizoma O 0
Rhei O 0
( O 0
rhubarb O 0
) O 0
. O 0

The O 0
renal B-Disease 0
injury I-Disease 0
was O 0
probably O 0
aggravated O 0
by O 0
the O 0
concomitant O 0
intake O 0
of O 0
a O 0
non O 0
- O 0
steroidal O 0
anti O 0
- O 0
inflammatory O 0
drug O 0
, O 0
diclofenac B-Chemical 0
. O 0

Renal O 0
pathology O 0
was O 0
that O 0
of O 0
hypocellular O 0
interstitial O 0
fibrosis B-Disease 0
. O 0

Spontaneous O 0
renal O 0
recovery O 0
occurred O 0
upon O 0
cessation O 0
of O 0
the O 0
slimming O 0
pills O 0
, O 0
but O 0
mild O 0
interstitial O 0
fibrosis B-Disease 0
and O 0
tubular O 0
atrophy B-Disease 0
was O 0
still O 0
evident O 0
histologically O 0
4 O 0
months O 0
later O 0
. O 0

Although O 0
a O 0
causal O 0
relationship O 0
between O 0
the O 0
use O 0
of O 0
an O 0
anthraquinone B-Chemical 0
- O 0
containing O 0
herbal O 0
agent O 0
and O 0
renal B-Disease 0
injury I-Disease 0
remains O 0
to O 0
be O 0
proven O 0
, O 0
phytotherapy O 0
- O 0
associated O 0
interstitial O 0
nephropathy B-Disease 0
should O 0
be O 0
considered O 0
in O 0
patients O 0
who O 0
present O 0
with O 0
unexplained O 0
renal B-Disease 0
failure I-Disease 0
. O 0

Chloroacetaldehyde B-Chemical 0
as O 0
a O 0
sulfhydryl B-Chemical 0
reagent O 0
: O 0
the O 0
role O 0
of O 0
critical O 0
thiol B-Chemical 0
groups O 0
in O 0
ifosfamide B-Chemical 0
nephropathy B-Disease 0
. O 0

Chloroacetaldehyde B-Chemical 0
( O 0
CAA B-Chemical 0
) O 0
is O 0
a O 0
metabolite O 0
of O 0
the O 0
alkylating O 0
agent O 0
ifosfamide B-Chemical 0
( O 0
IFO B-Chemical 0
) O 0
and O 0
putatively O 0
responsible O 0
for O 0
renal B-Disease 0
damage I-Disease 0
following O 0
anti O 0
- O 0
tumor B-Disease 0
therapy O 0
with O 0
IFO B-Chemical 0
. O 0

Depletion O 0
of O 0
sulfhydryl B-Chemical 0
( O 0
SH B-Chemical 0
) O 0
groups O 0
has O 0
been O 0
reported O 0
from O 0
cell O 0
culture O 0
, O 0
animal O 0
and O 0
clinical O 0
studies O 0
. O 0

In O 0
this O 0
work O 0
the O 0
effect O 0
of O 0
CAA B-Chemical 0
on O 0
human O 0
proximal O 0
tubule O 0
cells O 0
in O 0
primary O 0
culture O 0
( O 0
hRPTEC O 0
) O 0
was O 0
investigated O 0
. O 0

Toxicity B-Disease 0
of O 0
CAA B-Chemical 0
was O 0
determined O 0
by O 0
protein O 0
content O 0
, O 0
cell O 0
number O 0
, O 0
LDH O 0
release O 0
, O 0
trypan B-Chemical 0
blue I-Chemical 0
exclusion O 0
assay O 0
and O 0
caspase O 0
- O 0
3 O 0
activity O 0
. O 0

Free O 0
thiols B-Chemical 0
were O 0
measured O 0
by O 0
the O 0
method O 0
of O 0
Ellman O 0
. O 0

CAA B-Chemical 0
reduced O 0
hRPTEC O 0
cell O 0
number O 0
and O 0
protein O 0
, O 0
induced O 0
a O 0
loss O 0
in O 0
free O 0
intracellular O 0
thiols B-Chemical 0
and O 0
an O 0
increase O 0
in O 0
necrosis B-Disease 0
markers O 0
. O 0

CAA B-Chemical 0
but O 0
not O 0
acrolein B-Chemical 0
inhibited O 0
the O 0
cysteine B-Chemical 0
proteases O 0
caspase O 0
- O 0
3 O 0
, O 0
caspase O 0
- O 0
8 O 0
and O 0
cathepsin O 0
B O 0
. O 0

Caspase O 0
activation O 0
by O 0
cisplatin B-Chemical 0
was O 0
inhibited O 0
by O 0
CAA B-Chemical 0
. O 0

In O 0
cells O 0
stained O 0
with O 0
fluorescent O 0
dyes O 0
targeting O 0
lysosomes O 0
, O 0
CAA B-Chemical 0
induced O 0
an O 0
increase O 0
in O 0
lysosomal O 0
size O 0
and O 0
lysosomal O 0
leakage O 0
. O 0

The O 0
effects O 0
of O 0
CAA B-Chemical 0
on O 0
cysteine B-Chemical 0
protease O 0
activities O 0
and O 0
thiols B-Chemical 0
could O 0
be O 0
reproduced O 0
in O 0
cell O 0
lysate O 0
. O 0

Acidification O 0
, O 0
which O 0
slowed O 0
the O 0
reaction O 0
of O 0
CAA B-Chemical 0
with O 0
thiol B-Chemical 0
donors O 0
, O 0
could O 0
also O 0
attenuate O 0
effects O 0
of O 0
CAA B-Chemical 0
on O 0
necrosis B-Disease 0
markers O 0
, O 0
thiol B-Chemical 0
depletion O 0
and O 0
cysteine B-Chemical 0
protease O 0
inhibition O 0
in O 0
living O 0
cells O 0
. O 0

Thus O 0
, O 0
CAA B-Chemical 0
directly O 0
reacts O 0
with O 0
cellular O 0
protein O 0
and O 0
non O 0
- O 0
protein O 0
thiols B-Chemical 0
, O 0
mediating O 0
its O 0
toxicity B-Disease 0
on O 0
hRPTEC O 0
. O 0

This O 0
effect O 0
can O 0
be O 0
reduced O 0
by O 0
acidification O 0
. O 0

Therefore O 0
, O 0
urinary O 0
acidification O 0
could O 0
be O 0
an O 0
option O 0
to O 0
prevent O 0
IFO B-Chemical 0
nephropathy B-Disease 0
in O 0
patients O 0
. O 0

Stereological O 0
methods O 0
reveal O 0
the O 0
robust O 0
size O 0
and O 0
stability O 0
of O 0
ectopic O 0
hilar O 0
granule O 0
cells O 0
after O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
status B-Disease 0
epilepticus I-Disease 0
in O 0
the O 0
adult O 0
rat O 0
. O 0

Following O 0
status B-Disease 0
epilepticus I-Disease 0
in O 0
the O 0
rat O 0
, O 0
dentate O 0
granule O 0
cell O 0
neurogenesis O 0
increases O 0
greatly O 0
, O 0
and O 0
many O 0
of O 0
the O 0
new O 0
neurons O 0
appear O 0
to O 0
develop O 0
ectopically O 0
, O 0
in O 0
the O 0
hilar O 0
region O 0
of O 0
the O 0
hippocampal O 0
formation O 0
. O 0

It O 0
has O 0
been O 0
suggested O 0
that O 0
the O 0
ectopic O 0
hilar O 0
granule O 0
cells O 0
could O 0
contribute O 0
to O 0
the O 0
spontaneous O 0
seizures B-Disease 0
that O 0
ultimately O 0
develop O 0
after O 0
status B-Disease 0
epilepticus I-Disease 0
. O 0

However O 0
, O 0
the O 0
population O 0
has O 0
never O 0
been O 0
quantified O 0
, O 0
so O 0
it O 0
is O 0
unclear O 0
whether O 0
it O 0
is O 0
substantial O 0
enough O 0
to O 0
have O 0
a O 0
strong O 0
influence O 0
on O 0
epileptogenesis O 0
. O 0

To O 0
quantify O 0
this O 0
population O 0
, O 0
the O 0
total O 0
number O 0
of O 0
ectopic O 0
hilar O 0
granule O 0
cells O 0
was O 0
estimated O 0
using O 0
unbiased O 0
stereology O 0
at O 0
different O 0
times O 0
after O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
status B-Disease 0
epilepticus I-Disease 0
. O 0

The O 0
number O 0
of O 0
hilar O 0
neurons O 0
immunoreactive O 0
for O 0
Prox O 0
- O 0
1 O 0
, O 0
a O 0
granule O 0
- O 0
cell O 0
- O 0
specific O 0
marker O 0
, O 0
was O 0
estimated O 0
using O 0
the O 0
optical O 0
fractionator O 0
method O 0
. O 0

The O 0
results O 0
indicate O 0
that O 0
the O 0
size O 0
of O 0
the O 0
hilar O 0
ectopic O 0
granule O 0
cell O 0
population O 0
after O 0
status B-Disease 0
epilepticus I-Disease 0
is O 0
substantial O 0
, O 0
and O 0
stable O 0
over O 0
time O 0
. O 0

Interestingly O 0
, O 0
the O 0
size O 0
of O 0
the O 0
population O 0
appears O 0
to O 0
be O 0
correlated O 0
with O 0
the O 0
frequency O 0
of O 0
behavioral O 0
seizures B-Disease 0
, O 0
because O 0
animals O 0
with O 0
more O 0
ectopic O 0
granule O 0
cells O 0
in O 0
the O 0
hilus O 0
have O 0
more O 0
frequent O 0
behavioral O 0
seizures B-Disease 0
. O 0

The O 0
hilar O 0
ectopic O 0
granule O 0
cell O 0
population O 0
does O 0
not O 0
appear O 0
to O 0
vary O 0
systematically O 0
across O 0
the O 0
septotemporal O 0
axis O 0
, O 0
although O 0
it O 0
is O 0
associated O 0
with O 0
an O 0
increase O 0
in O 0
volume O 0
of O 0
the O 0
hilus O 0
. O 0

The O 0
results O 0
provide O 0
new O 0
insight O 0
into O 0
the O 0
potential O 0
role O 0
of O 0
ectopic O 0
hilar O 0
granule O 0
cells O 0
in O 0
the O 0
pilocarpine B-Chemical 0
model O 0
of O 0
temporal B-Disease 0
lobe I-Disease 0
epilepsy I-Disease 0
. O 0

A O 0
prospective O 0
, O 0
open O 0
- O 0
label O 0
trial O 0
of O 0
galantamine B-Chemical 0
in O 0
autistic B-Disease 0
disorder I-Disease 0
. O 0

OBJECTIVE O 0
: O 0
Post O 0
- O 0
mortem O 0
studies O 0
have O 0
reported O 0
abnormalities O 0
of O 0
the O 0
cholinergic O 0
system O 0
in O 0
autism B-Disease 0
. O 0

The O 0
purpose O 0
of O 0
this O 0
study O 0
was O 0
to O 0
assess O 0
the O 0
use O 0
of O 0
galantamine B-Chemical 0
, O 0
an O 0
acetylcholinesterase O 0
inhibitor O 0
and O 0
nicotinic O 0
receptor O 0
modulator O 0
, O 0
in O 0
the O 0
treatment O 0
of O 0
interfering O 0
behaviors O 0
in O 0
children O 0
with O 0
autism B-Disease 0
. O 0

METHODS O 0
: O 0
Thirteen O 0
medication O 0
- O 0
free O 0
children O 0
with O 0
autism B-Disease 0
( O 0
mean O 0
age O 0
, O 0
8 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
5 O 0
years O 0
) O 0
participated O 0
in O 0
a O 0
12 O 0
- O 0
week O 0
, O 0
open O 0
- O 0
label O 0
trial O 0
of O 0
galantamine B-Chemical 0
. O 0

Patients O 0
were O 0
rated O 0
monthly O 0
by O 0
parents O 0
on O 0
the O 0
Aberrant O 0
Behavior O 0
Checklist O 0
( O 0
ABC O 0
) O 0
and O 0
the O 0
Conners O 0
' O 0
Parent O 0
Rating O 0
Scale O 0
- O 0
Revised O 0
, O 0
and O 0
by O 0
a O 0
physician O 0
using O 0
the O 0
Children O 0
' O 0
s O 0
Psychiatric O 0
Rating O 0
Scale O 0
and O 0
the O 0
Clinical O 0
Global O 0
Impressions O 0
scale O 0
. O 0

RESULTS O 0
: O 0
Patients O 0
showed O 0
a O 0
significant O 0
reduction O 0
in O 0
parent O 0
- O 0
rated O 0
irritability B-Disease 0
and O 0
social O 0
withdrawal O 0
on O 0
the O 0
ABC O 0
as O 0
well O 0
as O 0
significant O 0
improvements O 0
in O 0
emotional O 0
lability O 0
and O 0
inattention O 0
on O 0
the O 0
Conners O 0
' O 0
Parent O 0
Rating O 0
Scale O 0
- O 0
- O 0
Revised O 0
. O 0

Similarly O 0
, O 0
clinician O 0
ratings O 0
showed O 0
reductions O 0
in O 0
the O 0
anger O 0
subscale O 0
of O 0
the O 0
Children O 0
' O 0
s O 0
Psychiatric O 0
Rating O 0
Scale O 0
. O 0

Eight O 0
of O 0
13 O 0
participants O 0
were O 0
rated O 0
as O 0
responders O 0
on O 0
the O 0
basis O 0
of O 0
their O 0
improvement O 0
scores O 0
on O 0
the O 0
Clinical O 0
Global O 0
Impressions O 0
scale O 0
. O 0

Overall O 0
, O 0
galantamine B-Chemical 0
was O 0
well O 0
- O 0
tolerated O 0
, O 0
with O 0
no O 0
significant O 0
adverse O 0
effects O 0
apart O 0
from O 0
headaches B-Disease 0
in O 0
one O 0
patient O 0
. O 0

CONCLUSION O 0
: O 0
In O 0
this O 0
open O 0
trial O 0
, O 0
galantamine B-Chemical 0
was O 0
well O 0
- O 0
tolerated O 0
and O 0
appeared O 0
to O 0
be O 0
beneficial O 0
for O 0
the O 0
treatment O 0
of O 0
interfering O 0
behaviors O 0
in O 0
children O 0
with O 0
autism B-Disease 0
, O 0
particularly O 0
aggression B-Disease 0
, O 0
behavioral B-Disease 0
dyscontrol I-Disease 0
, O 0
and O 0
inattention B-Disease 0
. O 0

Further O 0
controlled O 0
trials O 0
are O 0
warranted O 0
. O 0

Randomized O 0
comparison O 0
of O 0
olanzapine B-Chemical 0
versus O 0
risperidone B-Chemical 0
for O 0
the O 0
treatment O 0
of O 0
first O 0
- O 0
episode O 0
schizophrenia B-Disease 0
: O 0
4 O 0
- O 0
month O 0
outcomes O 0
. O 0

OBJECTIVE O 0
: O 0
The O 0
authors O 0
compared O 0
4 O 0
- O 0
month O 0
treatment O 0
outcomes O 0
for O 0
olanzapine B-Chemical 0
versus O 0
risperidone B-Chemical 0
in O 0
patients O 0
with O 0
first O 0
- O 0
episode O 0
schizophrenia B-Disease 0
spectrum O 0
disorders O 0
. O 0

METHOD O 0
: O 0
One O 0
hundred O 0
twelve O 0
subjects O 0
( O 0
70 O 0
% O 0
male O 0
; O 0
mean O 0
age O 0
= O 0
23 O 0
. O 0
3 O 0
years O 0
[ O 0
SD O 0
= O 0
5 O 0
. O 0
1 O 0
] O 0
) O 0
with O 0
first O 0
- O 0
episode O 0
schizophrenia B-Disease 0
( O 0
75 O 0
% O 0
) O 0
, O 0
schizophreniform B-Disease 0
disorder I-Disease 0
( O 0
17 O 0
% O 0
) O 0
, O 0
or O 0
schizoaffective B-Disease 0
disorder I-Disease 0
( O 0
8 O 0
% O 0
) O 0
were O 0
randomly O 0
assigned O 0
to O 0
treatment O 0
with O 0
olanzapine B-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
- O 0
20 O 0
mg O 0
/ O 0
day O 0
) O 0
or O 0
risperidone B-Chemical 0
( O 0
1 O 0
- O 0
6 O 0
mg O 0
/ O 0
day O 0
) O 0
. O 0

RESULTS O 0
: O 0
Response O 0
rates O 0
did O 0
not O 0
significantly O 0
differ O 0
between O 0
olanzapine B-Chemical 0
( O 0
43 O 0
. O 0
7 O 0
% O 0
, O 0
95 O 0
% O 0
CI O 0
= O 0
28 O 0
. O 0
8 O 0
% O 0
- O 0
58 O 0
. O 0
6 O 0
% O 0
) O 0
and O 0
risperidone B-Chemical 0
( O 0
54 O 0
. O 0
3 O 0
% O 0
, O 0
95 O 0
% O 0
CI O 0
= O 0
39 O 0
. O 0
9 O 0
% O 0
- O 0
68 O 0
. O 0
7 O 0
% O 0
) O 0
. O 0

Among O 0
those O 0
responding O 0
to O 0
treatment O 0
, O 0
more O 0
subjects O 0
in O 0
the O 0
olanzapine B-Chemical 0
group O 0
( O 0
40 O 0
. O 0
9 O 0
% O 0
, O 0
95 O 0
% O 0
CI O 0
= O 0
16 O 0
. O 0
8 O 0
% O 0
- O 0
65 O 0
. O 0
0 O 0
% O 0
) O 0
than O 0
in O 0
the O 0
risperidone B-Chemical 0
group O 0
( O 0
18 O 0
. O 0
9 O 0
% O 0
, O 0
95 O 0
% O 0
CI O 0
= O 0
0 O 0
% O 0
- O 0
39 O 0
. O 0
2 O 0
% O 0
) O 0
had O 0
subsequent O 0
ratings O 0
not O 0
meeting O 0
response O 0
criteria O 0
. O 0

Negative O 0
symptom O 0
outcomes O 0
and O 0
measures O 0
of O 0
parkinsonism B-Disease 0
and O 0
akathisia B-Disease 0
did O 0
not O 0
differ O 0
between O 0
medications O 0
. O 0

Extrapyramidal B-Disease 0
symptom I-Disease 0
severity O 0
scores O 0
were O 0
1 O 0
. O 0
4 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
1 O 0
. O 0
2 O 0
- O 0
1 O 0
. O 0
6 O 0
) O 0
with O 0
risperidone B-Chemical 0
and O 0
1 O 0
. O 0
2 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
1 O 0
. O 0
0 O 0
- O 0
1 O 0
. O 0
4 O 0
) O 0
with O 0
olanzapine B-Chemical 0
. O 0

Significantly O 0
more O 0
weight B-Disease 0
gain I-Disease 0
occurred O 0
with O 0
olanzapine B-Chemical 0
than O 0
with O 0
risperidone B-Chemical 0
: O 0
the O 0
increase O 0
in O 0
weight O 0
at O 0
4 O 0
months O 0
relative O 0
to O 0
baseline O 0
weight O 0
was O 0
17 O 0
. O 0
3 O 0
% O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
14 O 0
. O 0
2 O 0
% O 0
- O 0
20 O 0
. O 0
5 O 0
% O 0
) O 0
with O 0
olanzapine B-Chemical 0
and O 0
11 O 0
. O 0
3 O 0
% O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
8 O 0
. O 0
4 O 0
% O 0
- O 0
14 O 0
. O 0
3 O 0
% O 0
) O 0
with O 0
risperidone B-Chemical 0
. O 0

Body O 0
mass O 0
index O 0
at O 0
baseline O 0
and O 0
at O 0
4 O 0
months O 0
was O 0
24 O 0
. O 0
3 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
22 O 0
. O 0
8 O 0
- O 0
25 O 0
. O 0
7 O 0
) O 0
versus O 0
28 O 0
. O 0
2 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
26 O 0
. O 0
7 O 0
- O 0
29 O 0
. O 0
7 O 0
) O 0
with O 0
olanzapine B-Chemical 0
and O 0
23 O 0
. O 0
9 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
22 O 0
. O 0
5 O 0
- O 0
25 O 0
. O 0
3 O 0
) O 0
versus O 0
26 O 0
. O 0
7 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
25 O 0
. O 0
2 O 0
- O 0
28 O 0
. O 0
2 O 0
) O 0
with O 0
risperidone B-Chemical 0
. O 0

CONCLUSIONS O 0
: O 0
Clinical O 0
outcomes O 0
with O 0
risperidone B-Chemical 0
were O 0
equal O 0
to O 0
those O 0
with O 0
olanzapine B-Chemical 0
, O 0
and O 0
response O 0
may O 0
be O 0
more O 0
stable O 0
. O 0

Olanzapine B-Chemical 0
may O 0
have O 0
an O 0
advantage O 0
for O 0
motor O 0
side O 0
effects O 0
. O 0

Both O 0
medications O 0
caused O 0
substantial O 0
rapid O 0
weight B-Disease 0
gain I-Disease 0
, O 0
but O 0
weight B-Disease 0
gain I-Disease 0
was O 0
greater O 0
with O 0
olanzapine B-Chemical 0
. O 0

Early O 0
paracentral O 0
visual B-Disease 0
field I-Disease 0
loss I-Disease 0
in O 0
patients O 0
taking O 0
hydroxychloroquine B-Chemical 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
review O 0
the O 0
natural O 0
history O 0
and O 0
ocular O 0
and O 0
systemic O 0
adverse O 0
effects O 0
of O 0
patients O 0
taking O 0
hydroxychloroquine B-Chemical 0
sulfate I-Chemical 0
who O 0
attended O 0
an O 0
ophthalmic O 0
screening O 0
program O 0
. O 0

DESIGN O 0
: O 0
Retrospective O 0
study O 0
. O 0

RESULTS O 0
: O 0
Records O 0
of O 0
262 O 0
patients O 0
who O 0
were O 0
taking O 0
hydroxychloroquine B-Chemical 0
and O 0
screened O 0
in O 0
the O 0
Department O 0
of O 0
Ophthalmology O 0
were O 0
reviewed O 0
. O 0

Of O 0
the O 0
262 O 0
patients O 0
, O 0
14 O 0
( O 0
18 O 0
% O 0
) O 0
of O 0
76 O 0
who O 0
had O 0
stopped O 0
treatment O 0
at O 0
the O 0
time O 0
of O 0
the O 0
study O 0
experienced O 0
documented O 0
adverse O 0
effects O 0
. O 0

Systemic O 0
adverse O 0
effects O 0
occurred O 0
in O 0
8 O 0
patients O 0
( O 0
10 O 0
. O 0
5 O 0
% O 0
) O 0
and O 0
ocular O 0
adverse O 0
effects O 0
, O 0
in O 0
5 O 0
( O 0
6 O 0
. O 0
5 O 0
% O 0
) O 0
. O 0

Thirty O 0
- O 0
five O 0
patients O 0
( O 0
13 O 0
. O 0
4 O 0
% O 0
) O 0
had O 0
visual B-Disease 0
field I-Disease 0
abnormalities I-Disease 0
, O 0
which O 0
were O 0
attributed O 0
to O 0
hydroxychloroquine B-Chemical 0
treatment O 0
in O 0
4 O 0
patients O 0
( O 0
1 O 0
. O 0
5 O 0
% O 0
) O 0
. O 0

Three O 0
of O 0
the O 0
4 O 0
patients O 0
were O 0
taking O 0
less O 0
than O 0
6 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
per O 0
day O 0
and O 0
all O 0
patients O 0
had O 0
normal O 0
renal O 0
and O 0
liver O 0
function O 0
test O 0
results O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
current O 0
study O 0
used O 0
a O 0
protocol O 0
of O 0
visual O 0
acuity O 0
and O 0
color O 0
vision O 0
assessment O 0
, O 0
funduscopy O 0
, O 0
and O 0
Humphrey O 0
10 O 0
- O 0
2 O 0
visual O 0
field O 0
testing O 0
and O 0
shows O 0
that O 0
visual B-Disease 0
field I-Disease 0
defects I-Disease 0
appeared O 0
before O 0
any O 0
corresponding O 0
changes O 0
in O 0
any O 0
other O 0
tested O 0
clinical O 0
parameters O 0
; O 0
the O 0
defects O 0
were O 0
reproducible O 0
and O 0
the O 0
test O 0
parameters O 0
were O 0
reliable O 0
. O 0

Patients O 0
taking O 0
hydroxychloroquine B-Chemical 0
can O 0
demonstrate O 0
a O 0
toxic O 0
reaction O 0
in O 0
the O 0
retina O 0
despite O 0
the O 0
absence O 0
of O 0
known O 0
risk O 0
factors O 0
. O 0

Screening O 0
, O 0
including O 0
Humphrey O 0
10 O 0
- O 0
2 O 0
visual O 0
field O 0
assessment O 0
, O 0
is O 0
recommended O 0
2 O 0
years O 0
after O 0
the O 0
initial O 0
baseline O 0
and O 0
yearly O 0
thereafter O 0
. O 0

Peri O 0
- O 0
operative O 0
atrioventricular B-Disease 0
block I-Disease 0
as O 0
a O 0
result O 0
of O 0
chemotherapy O 0
with O 0
epirubicin B-Chemical 0
and O 0
paclitaxel B-Chemical 0
. O 0

A O 0
47 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
presented O 0
for O 0
mastectomy O 0
and O 0
immediate O 0
latissimus O 0
dorsi O 0
flap O 0
reconstruction O 0
having O 0
been O 0
diagnosed O 0
with O 0
carcinoma B-Disease 0
of I-Disease 0
the I-Disease 0
breast I-Disease 0
6 O 0
months O 0
previously O 0
. O 0

In O 0
the O 0
preceding O 0
months O 0
she O 0
had O 0
received O 0
neo O 0
- O 0
adjuvant O 0
chemotherapy O 0
with O 0
epirubicin B-Chemical 0
, O 0
paclitaxel B-Chemical 0
( O 0
Taxol B-Chemical 0
) O 0
and O 0
cyclophosphamide B-Chemical 0
. O 0

This O 0
had O 0
been O 0
apparently O 0
uncomplicated O 0
and O 0
she O 0
had O 0
maintained O 0
a O 0
remarkably O 0
high O 0
level O 0
of O 0
physical O 0
activity O 0
. O 0

She O 0
was O 0
found O 0
to O 0
be O 0
bradycardic B-Disease 0
at O 0
pre O 0
- O 0
operative O 0
assessment O 0
but O 0
had O 0
no O 0
cardiac O 0
symptoms O 0
. O 0

Second O 0
degree O 0
Mobitz O 0
type O 0
II O 0
atrioventricular B-Disease 0
block I-Disease 0
was O 0
diagnosed O 0
on O 0
electrocardiogram O 0
, O 0
and O 0
temporary O 0
transvenous O 0
ventricular O 0
pacing O 0
instituted O 0
in O 0
the O 0
peri O 0
- O 0
operative O 0
period O 0
. O 0

We O 0
discuss O 0
how O 0
evidence O 0
- O 0
based O 0
guidelines O 0
would O 0
not O 0
have O 0
been O 0
helpful O 0
in O 0
this O 0
case O 0
, O 0
and O 0
how O 0
chemotherapy O 0
can O 0
exhibit O 0
substantial O 0
cardiotoxicity B-Disease 0
that O 0
may O 0
develop O 0
over O 0
many O 0
years O 0
. O 0

We O 0
suggest O 0
that O 0
patients O 0
who O 0
have O 0
received O 0
chemotherapy O 0
at O 0
any O 0
time O 0
should O 0
have O 0
a O 0
pre O 0
- O 0
operative O 0
electrocardiogram O 0
even O 0
if O 0
they O 0
are O 0
asymptomatic O 0
. O 0

Risks O 0
and O 0
benefits O 0
of O 0
COX B-Chemical 0
- I-Chemical 0
2 I-Chemical 0
inhibitors I-Chemical 0
vs O 0
non O 0
- O 0
selective O 0
NSAIDs O 0
: O 0
does O 0
their O 0
cardiovascular O 0
risk O 0
exceed O 0
their O 0
gastrointestinal O 0
benefit O 0
? O 0

A O 0
retrospective O 0
cohort O 0
study O 0
. O 0

OBJECTIVES O 0
: O 0
The O 0
risk O 0
of O 0
acute B-Disease 0
myocardial I-Disease 0
infarction I-Disease 0
( O 0
AMI B-Disease 0
) O 0
with O 0
COX B-Chemical 0
- I-Chemical 0
2 I-Chemical 0
inhibitors I-Chemical 0
may O 0
offset O 0
their O 0
gastrointestinal O 0
( O 0
GI O 0
) O 0
benefit O 0
compared O 0
with O 0
non O 0
- O 0
selective O 0
( O 0
NS O 0
) O 0
non B-Chemical 0
- I-Chemical 0
steroidal I-Chemical 0
anti I-Chemical 0
- I-Chemical 0
inflammatory I-Chemical 0
drugs I-Chemical 0
( O 0
NSAIDs O 0
) O 0
. O 0

We O 0
aimed O 0
to O 0
compare O 0
the O 0
risks O 0
of O 0
hospitalization O 0
for O 0
AMI B-Disease 0
and O 0
GI B-Disease 0
bleeding I-Disease 0
among O 0
elderly O 0
patients O 0
using O 0
COX B-Chemical 0
- I-Chemical 0
2 I-Chemical 0
inhibitors I-Chemical 0
, O 0
NS O 0
- O 0
NSAIDs O 0
and O 0
acetaminophen B-Chemical 0
. O 0

METHODS O 0
: O 0
We O 0
conducted O 0
a O 0
retrospective O 0
cohort O 0
study O 0
using O 0
administrative O 0
data O 0
of O 0
patients O 0
> O 0
or O 0
= O 0
65 O 0
years O 0
of O 0
age O 0
who O 0
filled O 0
a O 0
prescription O 0
for O 0
NSAID O 0
or O 0
acetaminophen B-Chemical 0
during O 0
1999 O 0
- O 0
2002 O 0
. O 0

Outcomes O 0
were O 0
compared O 0
using O 0
Cox O 0
regression O 0
models O 0
with O 0
time O 0
- O 0
dependent O 0
exposures O 0
. O 0

RESULTS O 0
: O 0
Person O 0
- O 0
years O 0
of O 0
exposure O 0
among O 0
non O 0
- O 0
users O 0
of O 0
aspirin B-Chemical 0
were O 0
: O 0
75 O 0
, O 0
761 O 0
to O 0
acetaminophen B-Chemical 0
, O 0
42 O 0
, O 0
671 O 0
to O 0
rofecoxib B-Chemical 0
65 O 0
, O 0
860 O 0
to O 0
celecoxib B-Chemical 0
, O 0
and O 0
37 O 0
, O 0
495 O 0
to O 0
NS O 0
- O 0
NSAIDs O 0
. O 0

Among O 0
users O 0
of O 0
aspirin B-Chemical 0
, O 0
they O 0
were O 0
: O 0
14 O 0
, O 0
671 O 0
to O 0
rofecoxib B-Chemical 0
, O 0
22 O 0
, O 0
875 O 0
to O 0
celecoxib B-Chemical 0
, O 0
9 O 0
, O 0
832 O 0
to O 0
NS O 0
- O 0
NSAIDs O 0
and O 0
38 O 0
, O 0
048 O 0
to O 0
acetaminophen B-Chemical 0
. O 0

Among O 0
non O 0
- O 0
users O 0
of O 0
aspirin B-Chemical 0
, O 0
the O 0
adjusted O 0
hazard O 0
ratios O 0
( O 0
95 O 0
% O 0
confidence O 0
interval O 0
) O 0
of O 0
hospitalization O 0
for O 0
AMI B-Disease 0
/ O 0
GI O 0
vs O 0
the O 0
acetaminophen B-Chemical 0
( O 0
with O 0
no O 0
aspirin B-Chemical 0
) O 0
group O 0
were O 0
: O 0
rofecoxib B-Chemical 0
1 O 0
. O 0
27 O 0
( O 0
1 O 0
. O 0
13 O 0
, O 0
1 O 0
. O 0
42 O 0
) O 0
, O 0
celecoxib B-Chemical 0
0 O 0
. O 0
93 O 0
( O 0
0 O 0
. O 0
83 O 0
, O 0
1 O 0
. O 0
03 O 0
) O 0
, O 0
naproxen B-Chemical 0
1 O 0
. O 0
59 O 0
( O 0
1 O 0
. O 0
31 O 0
, O 0
1 O 0
. O 0
93 O 0
) O 0
, O 0
diclofenac B-Chemical 0
1 O 0
. O 0
17 O 0
( O 0
0 O 0
. O 0
99 O 0
, O 0
1 O 0
. O 0
38 O 0
) O 0
and O 0
ibuprofen B-Chemical 0
1 O 0
. O 0
05 O 0
( O 0
0 O 0
. O 0
74 O 0
, O 0
1 O 0
. O 0
51 O 0
) O 0
. O 0

Among O 0
users O 0
of O 0
aspirin B-Chemical 0
, O 0
they O 0
were O 0
: O 0
rofecoxib B-Chemical 0
1 O 0
. O 0
73 O 0
( O 0
1 O 0
. O 0
52 O 0
, O 0
1 O 0
. O 0
98 O 0
) O 0
, O 0
celecoxib B-Chemical 0
1 O 0
. O 0
34 O 0
( O 0
1 O 0
. O 0
19 O 0
, O 0
1 O 0
. O 0
52 O 0
) O 0
, O 0
ibuprofen B-Chemical 0
1 O 0
. O 0
51 O 0
( O 0
0 O 0
. O 0
95 O 0
, O 0
2 O 0
. O 0
41 O 0
) O 0
, O 0
diclofenac B-Chemical 0
1 O 0
. O 0
69 O 0
( O 0
1 O 0
. O 0
35 O 0
, O 0
2 O 0
. O 0
10 O 0
) O 0
, O 0
naproxen B-Chemical 0
1 O 0
. O 0
35 O 0
( O 0
0 O 0
. O 0
97 O 0
, O 0
1 O 0
. O 0
88 O 0
) O 0
and O 0
acetaminophen B-Chemical 0
1 O 0
. O 0
29 O 0
( O 0
1 O 0
. O 0
17 O 0
, O 0
1 O 0
. O 0
42 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
Among O 0
non O 0
- O 0
users O 0
of O 0
aspirin B-Chemical 0
, O 0
naproxen B-Chemical 0
seemed O 0
to O 0
carry O 0
the O 0
highest O 0
risk O 0
for O 0
AMI B-Disease 0
/ O 0
GI B-Disease 0
bleeding I-Disease 0
. O 0

The O 0
AMI B-Disease 0
/ O 0
GI O 0
toxicity B-Disease 0
of O 0
celecoxib B-Chemical 0
was O 0
similar O 0
to O 0
that O 0
of O 0
acetaminophen B-Chemical 0
and O 0
seemed O 0
to O 0
be O 0
better O 0
than O 0
those O 0
of O 0
rofecoxib B-Chemical 0
and O 0
NS O 0
- O 0
NSAIDs O 0
. O 0

Among O 0
users O 0
of O 0
aspirin B-Chemical 0
, O 0
both O 0
celecoxib B-Chemical 0
and O 0
naproxen B-Chemical 0
seemed O 0
to O 0
be O 0
the O 0
least O 0
toxic O 0
. O 0

Quinine B-Chemical 0
- O 0
induced O 0
arrhythmia B-Disease 0
in O 0
a O 0
patient O 0
with O 0
severe B-Disease 0
malaria I-Disease 0
. O 0

It O 0
was O 0
reported O 0
that O 0
there O 0
was O 0
a O 0
case O 0
of O 0
severe B-Disease 0
malaria I-Disease 0
patient O 0
with O 0
jaundice B-Disease 0
who O 0
presented O 0
with O 0
arrhythmia B-Disease 0
( O 0
premature B-Disease 0
ventricular I-Disease 0
contraction I-Disease 0
) O 0
while O 0
getting O 0
quinine B-Chemical 0
infusion O 0
was O 0
reported O 0
. O 0

A O 0
man O 0
, O 0
25 O 0
years O 0
old O 0
, O 0
was O 0
admitted O 0
to O 0
hospital O 0
with O 0
high O 0
fever B-Disease 0
, O 0
chill B-Disease 0
, O 0
vomiting B-Disease 0
, O 0
jaundice B-Disease 0
. O 0

The O 0
patient O 0
was O 0
fully O 0
conscious O 0
, O 0
blood O 0
pressure O 0
120 O 0
/ O 0
80 O 0
mmHg O 0
, O 0
pulse O 0
rate O 0
100 O 0
x O 0
/ O 0
minute O 0
, O 0
regular O 0
. O 0

On O 0
admission O 0
, O 0
laboratory O 0
examination O 0
showed O 0
Plasmodium O 0
falciparum O 0
( O 0
+ O 0
+ O 0
+ O 0
+ O 0
) O 0
, O 0
total O 0
bilirubin B-Chemical 0
8 O 0
. O 0
25 O 0
mg O 0
/ O 0
dL O 0
, O 0
conjugated O 0
bilirubin B-Chemical 0
4 O 0
. O 0
36 O 0
mg O 0
/ O 0
dL O 0
, O 0
unconjugated O 0
bilirubin B-Chemical 0
3 O 0
. O 0
89 O 0
mg O 0
/ O 0
dL O 0
, O 0
potassium B-Chemical 0
3 O 0
. O 0
52 O 0
meq O 0
/ O 0
L O 0
Patient O 0
was O 0
diagnosed O 0
as O 0
severe B-Disease 0
malaria I-Disease 0
with O 0
jaundice B-Disease 0
and O 0
got O 0
quinine B-Chemical 0
infusion O 0
in O 0
dextrose B-Chemical 0
5 O 0
% O 0
500 O 0
mg O 0
/ O 0
8 O 0
hour O 0
. O 0

On O 0
the O 0
second O 0
day O 0
the O 0
patient O 0
had O 0
vomitus B-Disease 0
, O 0
diarrhea B-Disease 0
, O 0
tinnitus B-Disease 0
, O 0
loss B-Disease 0
of I-Disease 0
hearing I-Disease 0
. O 0

After O 0
30 O 0
hours O 0
of O 0
quinine B-Chemical 0
infusion O 0
the O 0
patient O 0
felt O 0
palpitation B-Disease 0
and O 0
electrocardiography O 0
( O 0
ECG O 0
) O 0
recording O 0
showed O 0
premature B-Disease 0
ventricular I-Disease 0
contraction I-Disease 0
( O 0
PVC B-Disease 0
) O 0
> O 0
5 O 0
x O 0
/ O 0
minute O 0
, O 0
trigemini O 0
, O 0
constant O 0
type O 0
- O 0
- O 0
sinoatrial B-Disease 0
block I-Disease 0
, O 0
positive O 0
U O 0
wave O 0
. O 0

He O 0
was O 0
treated O 0
with O 0
lidocaine B-Chemical 0
50 O 0
mg O 0
intravenously O 0
followed O 0
by O 0
infusion O 0
1500 O 0
mg O 0
in O 0
dextrose B-Chemical 0
5 O 0
% O 0
/ O 0
24 O 0
hour O 0
and O 0
potassium B-Chemical 0
aspartate I-Chemical 0
tablet O 0
. O 0

Quinine B-Chemical 0
infusion O 0
was O 0
discontinued O 0
and O 0
changed O 0
with O 0
sulfate O 0
quinine B-Chemical 0
tablets O 0
. O 0

Three O 0
hours O 0
later O 0
the O 0
patient O 0
felt O 0
better O 0
, O 0
the O 0
frequency O 0
of O 0
PVC B-Disease 0
reduced O 0
to O 0
4 O 0
- O 0
5 O 0
x O 0
/ O 0
minute O 0
and O 0
on O 0
the O 0
third O 0
day O 0
ECG O 0
was O 0
normal O 0
, O 0
potassium B-Chemical 0
level O 0
was O 0
3 O 0
. O 0
34 O 0
meq O 0
/ O 0
L O 0
. O 0

He O 0
was O 0
discharged O 0
on O 0
7th O 0
day O 0
in O 0
good O 0
condition O 0
. O 0

Quinine B-Chemical 0
, O 0
like O 0
quinidine B-Chemical 0
, O 0
is O 0
a O 0
chincona O 0
alkaloid O 0
that O 0
has O 0
anti O 0
- O 0
arrhythmic B-Disease 0
property O 0
, O 0
although O 0
it O 0
also O 0
pro O 0
- O 0
arrhythmic B-Disease 0
that O 0
can O 0
cause O 0
various O 0
arrhythmias B-Disease 0
, O 0
including O 0
severe O 0
arrhythmia B-Disease 0
such O 0
as O 0
multiple O 0
PVC B-Disease 0
. O 0

Administration O 0
of O 0
parenteral O 0
quinine B-Chemical 0
must O 0
be O 0
done O 0
carefully O 0
and O 0
with O 0
good O 0
observation O 0
because O 0
of O 0
its O 0
pro O 0
- O 0
arrhythmic B-Disease 0
effect O 0
, O 0
especially O 0
in O 0
older O 0
patients O 0
who O 0
have O 0
heart B-Disease 0
diseases I-Disease 0
or O 0
patients O 0
with O 0
electrolyte B-Disease 0
disorder I-Disease 0
( O 0
hypokalemia B-Disease 0
) O 0
which O 0
frequently O 0
occurs O 0
due O 0
to O 0
vomiting B-Disease 0
and O 0
or O 0
diarrhea B-Disease 0
in O 0
malaria B-Disease 0
cases O 0
. O 0

Penicillamine B-Chemical 0
- O 0
related O 0
lichenoid B-Disease 0
dermatitis I-Disease 0
and O 0
utility O 0
of O 0
zinc B-Chemical 0
acetate I-Chemical 0
in O 0
a O 0
Wilson B-Disease 0
disease I-Disease 0
patient O 0
with O 0
hepatic O 0
presentation O 0
, O 0
anxiety B-Disease 0
and O 0
SPECT O 0
abnormalities O 0
. O 0

Wilson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
is O 0
an O 0
autosomal O 0
recessive O 0
disorder O 0
of O 0
hepatic O 0
copper B-Chemical 0
metabolism O 0
with O 0
consequent O 0
copper B-Chemical 0
accumulation O 0
and O 0
toxicity B-Disease 0
in O 0
many O 0
tissues O 0
and O 0
consequent O 0
hepatic B-Disease 0
, I-Disease 0
neurologic I-Disease 0
and I-Disease 0
psychiatric I-Disease 0
disorders I-Disease 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
Wilson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
with O 0
chronic B-Disease 0
liver I-Disease 0
disease I-Disease 0
; O 0
moreover O 0
, O 0
in O 0
our O 0
patient O 0
, O 0
presenting O 0
also O 0
with O 0
high O 0
levels O 0
of O 0
state O 0
anxiety B-Disease 0
without O 0
depression B-Disease 0
, O 0
99mTc O 0
- O 0
ECD O 0
- O 0
SPECT O 0
showed O 0
cortical O 0
hypoperfusion O 0
in O 0
frontal O 0
lobes O 0
, O 0
more O 0
marked O 0
on O 0
the O 0
left O 0
frontal O 0
lobe O 0
. O 0

During O 0
the O 0
follow O 0
- O 0
up O 0
of O 0
our O 0
patient O 0
, O 0
penicillamine B-Chemical 0
was O 0
interrupted O 0
after O 0
the O 0
appearance O 0
of O 0
a O 0
lichenoid B-Disease 0
dermatitis I-Disease 0
, O 0
and O 0
zinc B-Chemical 0
acetate I-Chemical 0
permitted O 0
to O 0
continue O 0
the O 0
successful O 0
treatment O 0
of O 0
the O 0
patient O 0
without O 0
side O 0
- O 0
effects O 0
. O 0

In O 0
our O 0
case O 0
the O 0
therapy O 0
with O 0
zinc B-Chemical 0
acetate I-Chemical 0
represented O 0
an O 0
effective O 0
treatment O 0
for O 0
a O 0
Wilson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
patient O 0
in O 0
which O 0
penicillamine B-Chemical 0
- O 0
related O 0
side O 0
effects O 0
appeared O 0
. O 0

The O 0
safety O 0
of O 0
the O 0
zinc B-Chemical 0
acetate I-Chemical 0
allowed O 0
us O 0
to O 0
avoid O 0
other O 0
potentially O 0
toxic O 0
chelating O 0
drugs O 0
; O 0
this O 0
observation O 0
is O 0
in O 0
line O 0
with O 0
the O 0
growing O 0
evidence O 0
on O 0
the O 0
efficacy O 0
of O 0
the O 0
drug O 0
in O 0
the O 0
treatment O 0
of O 0
Wilson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

Since O 0
most O 0
of O 0
Wilson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
penicillamine B-Chemical 0
- O 0
treated O 0
patients O 0
do O 0
not O 0
seem O 0
to O 0
develop O 0
this O 0
skin B-Disease 0
lesion I-Disease 0
, O 0
it O 0
could O 0
be O 0
conceivable O 0
that O 0
a O 0
specific O 0
genetic O 0
factor O 0
is O 0
involved O 0
in O 0
drug O 0
response O 0
. O 0

Further O 0
studies O 0
are O 0
needed O 0
for O 0
a O 0
better O 0
clarification O 0
of O 0
Wilson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
therapy O 0
, O 0
and O 0
in O 0
particular O 0
to O 0
differentiate O 0
specific O 0
therapies O 0
for O 0
different O 0
Wilson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
phenotypes O 0
. O 0

A O 0
dramatic O 0
drop B-Disease 0
in I-Disease 0
blood I-Disease 0
pressure I-Disease 0
following O 0
prehospital O 0
GTN B-Chemical 0
administration O 0
. O 0

A O 0
male O 0
in O 0
his O 0
sixties O 0
with O 0
no O 0
history O 0
of O 0
cardiac O 0
chest B-Disease 0
pain I-Disease 0
awoke O 0
with O 0
chest B-Disease 0
pain I-Disease 0
following O 0
an O 0
afternoon O 0
sleep O 0
. O 0

The O 0
patient O 0
did O 0
not O 0
self O 0
medicate O 0
. O 0

The O 0
patient O 0
' O 0
s O 0
observations O 0
were O 0
within O 0
normal O 0
limits O 0
, O 0
he O 0
was O 0
administered O 0
oxygen B-Chemical 0
via O 0
a O 0
face O 0
mask O 0
and O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
( O 0
GTN B-Chemical 0
) O 0
. O 0

Several O 0
minutes O 0
after O 0
the O 0
GTN B-Chemical 0
the O 0
patient O 0
experienced O 0
a O 0
sudden O 0
drop B-Disease 0
in I-Disease 0
blood I-Disease 0
pressure I-Disease 0
and O 0
heart O 0
rate O 0
, O 0
this O 0
was O 0
rectified O 0
by O 0
atropine B-Chemical 0
sulphate I-Chemical 0
and O 0
a O 0
fluid O 0
challenge O 0
. O 0

There O 0
was O 0
no O 0
further O 0
deterioration O 0
in O 0
the O 0
patient O 0
' O 0
s O 0
condition O 0
during O 0
transport O 0
to O 0
hospital O 0
. O 0

There O 0
are O 0
very O 0
few O 0
documented O 0
case O 0
like O 0
this O 0
in O 0
the O 0
prehospital O 0
scientific O 0
literature O 0
. O 0

The O 0
cause O 0
appears O 0
to O 0
be O 0
the O 0
Bezold O 0
- O 0
Jarish O 0
reflex O 0
, O 0
stimulation O 0
of O 0
the O 0
ventricular O 0
walls O 0
which O 0
in O 0
turn O 0
decreases O 0
sympathetic O 0
outflow O 0
from O 0
the O 0
vasomotor O 0
centre O 0
. O 0

Prehospital O 0
care O 0
providers O 0
who O 0
are O 0
managing O 0
any O 0
patient O 0
with O 0
a O 0
syncopal B-Disease 0
episode I-Disease 0
that O 0
fails O 0
to O 0
recover O 0
within O 0
a O 0
reasonable O 0
time O 0
frame O 0
should O 0
consider O 0
the O 0
Bezold O 0
- O 0
Jarisch O 0
reflex O 0
as O 0
the O 0
cause O 0
and O 0
manage O 0
the O 0
patient O 0
accordingly O 0
. O 0

Chronic O 0
lesion O 0
of O 0
rostral O 0
ventrolateral O 0
medulla O 0
in O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
. O 0

We O 0
studied O 0
the O 0
effects O 0
of O 0
chronic O 0
selective O 0
neuronal O 0
lesion O 0
of O 0
rostral O 0
ventrolateral O 0
medulla O 0
on O 0
mean O 0
arterial O 0
pressure O 0
, O 0
heart O 0
rate O 0
, O 0
and O 0
neurogenic O 0
tone O 0
in O 0
conscious O 0
, O 0
unrestrained O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
. O 0

The O 0
lesions O 0
were O 0
placed O 0
via O 0
bilateral O 0
microinjections O 0
of O 0
30 O 0
nmol O 0
/ O 0
200 O 0
nl O 0
N B-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
- I-Chemical 0
D I-Chemical 0
- I-Chemical 0
aspartic I-Chemical 0
acid I-Chemical 0
. O 0

The O 0
restimulation O 0
of O 0
this O 0
area O 0
with O 0
N B-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
- I-Chemical 0
D I-Chemical 0
- I-Chemical 0
aspartic I-Chemical 0
acid I-Chemical 0
15 O 0
days O 0
postlesion O 0
failed O 0
to O 0
produce O 0
a O 0
pressor O 0
response O 0
. O 0

One O 0
day O 0
postlesion O 0
, O 0
the O 0
resting O 0
mean O 0
arterial O 0
pressure O 0
was O 0
significantly O 0
decreased O 0
in O 0
lesioned O 0
rats O 0
when O 0
compared O 0
with O 0
sham O 0
rats O 0
( O 0
100 O 0
+ O 0
/ O 0
- O 0
7 O 0
versus O 0
173 O 0
+ O 0
/ O 0
- O 0
4 O 0
mm O 0
Hg O 0
, O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Fifteen O 0
days O 0
later O 0
, O 0
the O 0
lesioned O 0
group O 0
still O 0
showed O 0
values O 0
significantly O 0
lower O 0
than O 0
the O 0
sham O 0
group O 0
( O 0
150 O 0
+ O 0
/ O 0
- O 0
6 O 0
versus O 0
167 O 0
+ O 0
/ O 0
- O 0
5 O 0
mm O 0
Hg O 0
, O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

No O 0
significant O 0
heart O 0
rate O 0
differences O 0
were O 0
observed O 0
between O 0
the O 0
sham O 0
and O 0
lesioned O 0
groups O 0
. O 0

The O 0
ganglionic O 0
blocker O 0
trimethaphan B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
) O 0
caused O 0
similar O 0
reductions O 0
in O 0
mean O 0
arterial O 0
pressure O 0
in O 0
both O 0
lesioned O 0
and O 0
sham O 0
groups O 0
. O 0

The O 0
trimethaphan B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
was O 0
accompanied O 0
by O 0
a O 0
significant O 0
bradycardia B-Disease 0
in O 0
lesioned O 0
rats O 0
( O 0
- O 0
32 O 0
+ O 0
/ O 0
- O 0
13 O 0
beats O 0
per O 0
minute O 0
) O 0
but O 0
a O 0
tachycardia B-Disease 0
in O 0
sham O 0
rats O 0
( O 0
+ O 0
33 O 0
+ O 0
/ O 0
- O 0
12 O 0
beats O 0
per O 0
minute O 0
) O 0
1 O 0
day O 0
postlesion O 0
. O 0

Therefore O 0
, O 0
rostral O 0
ventrolateral O 0
medulla O 0
neurons O 0
appear O 0
to O 0
play O 0
a O 0
significant O 0
role O 0
in O 0
maintaining O 0
hypertension B-Disease 0
in O 0
conscious O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
. O 0

Spinal O 0
or O 0
suprabulbar O 0
structures O 0
could O 0
be O 0
responsible O 0
for O 0
the O 0
gradual O 0
recovery O 0
of O 0
the O 0
hypertension B-Disease 0
in O 0
the O 0
lesioned O 0
rats O 0
. O 0

Acute B-Disease 0
encephalopathy I-Disease 0
and O 0
cerebral B-Disease 0
vasospasm I-Disease 0
after O 0
multiagent O 0
chemotherapy O 0
including O 0
PEG B-Chemical 0
- I-Chemical 0
asparaginase I-Chemical 0
and O 0
intrathecal O 0
cytarabine B-Chemical 0
for O 0
the O 0
treatment O 0
of O 0
acute B-Disease 0
lymphoblastic I-Disease 0
leukemia I-Disease 0
. O 0

A O 0
7 O 0
- O 0
year O 0
- O 0
old O 0
girl O 0
with O 0
an O 0
unusual O 0
reaction O 0
to O 0
induction O 0
chemotherapy O 0
for O 0
precursor O 0
B O 0
- O 0
cell O 0
acute B-Disease 0
lymphoblastic I-Disease 0
leukemia I-Disease 0
( O 0
ALL B-Disease 0
) O 0
is O 0
described O 0
. O 0

The O 0
patient O 0
developed O 0
acute B-Disease 0
encephalopathy I-Disease 0
evidenced O 0
by O 0
behavioral O 0
changes O 0
, O 0
aphasia B-Disease 0
, O 0
incontinence B-Disease 0
, O 0
visual B-Disease 0
hallucinations I-Disease 0
, O 0
and O 0
right O 0
- O 0
sided O 0
weakness B-Disease 0
with O 0
diffuse O 0
cerebral B-Disease 0
vasospasm I-Disease 0
on O 0
magnetic O 0
resonance O 0
angiography O 0
after O 0
the O 0
administration O 0
of O 0
intrathecal O 0
cytarabine B-Chemical 0
. O 0

Vincristine B-Chemical 0
, O 0
dexamethasone B-Chemical 0
, O 0
and O 0
polyethylene B-Chemical 0
glycol I-Chemical 0
- I-Chemical 0
asparaginase I-Chemical 0
were O 0
also O 0
administered O 0
before O 0
the O 0
episode O 0
as O 0
part O 0
of O 0
induction O 0
therapy O 0
. O 0

Neurologic O 0
status O 0
returned O 0
to O 0
baseline O 0
within O 0
10 O 0
days O 0
of O 0
the O 0
acute O 0
event O 0
, O 0
and O 0
magnetic O 0
resonance O 0
angiography O 0
findings O 0
returned O 0
to O 0
normal O 0
4 O 0
months O 0
later O 0
. O 0

Comparison O 0
of O 0
valsartan B-Chemical 0
/ O 0
hydrochlorothiazide B-Chemical 0
combination O 0
therapy O 0
at O 0
doses O 0
up O 0
to O 0
320 O 0
/ O 0
25 O 0
mg O 0
versus O 0
monotherapy O 0
: O 0
a O 0
double O 0
- O 0
blind O 0
, O 0
placebo O 0
- O 0
controlled O 0
study O 0
followed O 0
by O 0
long O 0
- O 0
term O 0
combination O 0
therapy O 0
in O 0
hypertensive B-Disease 0
adults O 0
. O 0

BACKGROUND O 0
: O 0
One O 0
third O 0
of O 0
patients O 0
treated O 0
for O 0
hypertension B-Disease 0
attain O 0
adequate O 0
blood O 0
pressure O 0
( O 0
BP O 0
) O 0
control O 0
, O 0
and O 0
multidrug O 0
regimens O 0
are O 0
often O 0
required O 0
. O 0

Given O 0
the O 0
lifelong O 0
nature O 0
of O 0
hypertension B-Disease 0
, O 0
there O 0
is O 0
a O 0
need O 0
to O 0
evaluate O 0
the O 0
long O 0
- O 0
term O 0
efficacy O 0
and O 0
tolerability O 0
of O 0
higher O 0
doses O 0
of O 0
combination O 0
anti O 0
- O 0
hypertensive B-Disease 0
therapies O 0
. O 0

OBJECTIVE O 0
: O 0
This O 0
study O 0
investigated O 0
the O 0
efficacy O 0
and O 0
tolerability O 0
of O 0
valsartan B-Chemical 0
( O 0
VAL B-Chemical 0
) O 0
or O 0
hydrochlorothiazide B-Chemical 0
( O 0
HCTZ B-Chemical 0
) O 0
- O 0
monotherapy O 0
and O 0
higher O 0
- O 0
dose O 0
combinations O 0
in O 0
patients O 0
with O 0
essential B-Disease 0
hypertension I-Disease 0
. O 0

METHODS O 0
: O 0
The O 0
first O 0
part O 0
of O 0
this O 0
study O 0
was O 0
an O 0
8 O 0
- O 0
week O 0
, O 0
multicenter O 0
, O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
placebo O 0
controlled O 0
, O 0
parallel O 0
- O 0
group O 0
trial O 0
. O 0

Patients O 0
with O 0
essential B-Disease 0
hypertension I-Disease 0
( O 0
mean O 0
sitting O 0
diastolic O 0
BP O 0
[ O 0
MSDBP O 0
] O 0
, O 0
> O 0
or O 0
= O 0
95 O 0
mm O 0
Hg O 0
and O 0
< O 0
110 O 0
mm O 0
Hg O 0
) O 0
were O 0
randomized O 0
to O 0
1 O 0
of O 0
8 O 0
treatment O 0
groups O 0
: O 0
VAL B-Chemical 0
160 O 0
or O 0
320 O 0
mg O 0
; O 0
HCTZ B-Chemical 0
12 O 0
. O 0
5 O 0
or O 0
25 O 0
mg O 0
; O 0
VAL B-Chemical 0
/ O 0
HCTZ B-Chemical 0
160 O 0
/ O 0
12 O 0
. O 0
5 O 0
, O 0
320 O 0
/ O 0
12 O 0
. O 0
5 O 0
, O 0
or O 0
320 O 0
/ O 0
25 O 0
mg O 0
; O 0
or O 0
placebo O 0
. O 0

Mean O 0
changes O 0
in O 0
MSDBP O 0
and O 0
mean O 0
sitting O 0
systolic O 0
BP O 0
( O 0
MSSBP O 0
) O 0
were O 0
analyzed O 0
at O 0
the O 0
8 O 0
- O 0
week O 0
core O 0
study O 0
end O 0
point O 0
. O 0

VAL B-Chemical 0
/ O 0
HCTZ B-Chemical 0
320 O 0
/ O 0
12 O 0
. O 0
5 O 0
and O 0
320 O 0
/ O 0
25 O 0
mg O 0
were O 0
further O 0
investigated O 0
in O 0
a O 0
54 O 0
- O 0
week O 0
, O 0
open O 0
- O 0
label O 0
extension O 0
. O 0

Response O 0
was O 0
defined O 0
as O 0
MSDBP O 0
< O 0
90 O 0
mm O 0
Hg O 0
or O 0
a O 0
> O 0
or O 0
= O 0
10 O 0
mm O 0
Hg O 0
decrease O 0
compared O 0
to O 0
baseline O 0
. O 0

Control O 0
was O 0
defined O 0
as O 0
MSDBP O 0
< O 0
90 O 0
mm O 0
Hg O 0
compared O 0
with O 0
baseline O 0
. O 0

Tolerability O 0
was O 0
assessed O 0
by O 0
monitoring O 0
adverse O 0
events O 0
at O 0
randomization O 0
and O 0
all O 0
subsequent O 0
study O 0
visits O 0
and O 0
regular O 0
evaluation O 0
of O 0
hematology O 0
and O 0
blood O 0
chemistry O 0
. O 0

RESULTS O 0
: O 0
A O 0
total O 0
of O 0
1346 O 0
patients O 0
were O 0
randomized O 0
into O 0
the O 0
8 O 0
- O 0
week O 0
core O 0
study O 0
( O 0
734 O 0
men O 0
, O 0
612 O 0
women O 0
; O 0
924 O 0
white O 0
, O 0
291 O 0
black O 0
, O 0
23 O 0
Asian O 0
, O 0
108 O 0
other O 0
; O 0
mean O 0
age O 0
, O 0
52 O 0
. O 0
7 O 0
years O 0
; O 0
mean O 0
weight O 0
, O 0
92 O 0
. O 0
6 O 0
kg O 0
) O 0
. O 0

All O 0
active O 0
treatments O 0
were O 0
associated O 0
with O 0
significantly O 0
reduced O 0
MSSBP O 0
and O 0
MSDBP O 0
during O 0
the O 0
core O 0
8 O 0
- O 0
week O 0
study O 0
, O 0
with O 0
each O 0
monotherapy O 0
significantly O 0
contributing O 0
to O 0
the O 0
overall O 0
effect O 0
of O 0
combination O 0
therapy O 0
( O 0
VAL B-Chemical 0
and O 0
HCTZ B-Chemical 0
, O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Each O 0
combination O 0
was O 0
associated O 0
with O 0
significantly O 0
greater O 0
reductions O 0
in O 0
MSSBP O 0
and O 0
MSDBP O 0
compared O 0
with O 0
the O 0
monotherapies O 0
and O 0
placebo O 0
( O 0
all O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

The O 0
mean O 0
reduction O 0
in O 0
MSSBP O 0
/ O 0
MSDBP O 0
with O 0
VAL B-Chemical 0
/ O 0
HCTZ B-Chemical 0
320 O 0
/ O 0
25 O 0
mg O 0
was O 0
24 O 0
. O 0
7 O 0
/ O 0
16 O 0
. O 0
6 O 0
mm O 0
Hg O 0
, O 0
compared O 0
with O 0
5 O 0
. O 0
9 O 0
/ O 0
7 O 0
. O 0
0 O 0
mm O 0
Hg O 0
with O 0
placebo O 0
. O 0

The O 0
reduction O 0
in O 0
MSSBP O 0
was O 0
significantly O 0
greater O 0
with O 0
VAL B-Chemical 0
/ O 0
HCTZ B-Chemical 0
320 O 0
/ O 0
25 O 0
mg O 0
compared O 0
with O 0
VAL B-Chemical 0
/ O 0
HCTZ B-Chemical 0
160 O 0
/ O 0
12 O 0
. O 0
5 O 0
mg O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
002 O 0
) O 0
. O 0

Rates O 0
of O 0
response O 0
and O 0
BP O 0
control O 0
were O 0
significantly O 0
higher O 0
in O 0
the O 0
groups O 0
that O 0
received O 0
combination O 0
treatment O 0
compared O 0
with O 0
those O 0
that O 0
received O 0
monotherapy O 0
. O 0

The O 0
incidence O 0
of O 0
hypokalemia B-Disease 0
was O 0
lower O 0
with O 0
VAL B-Chemical 0
/ O 0
HCTZ B-Chemical 0
combinations O 0
( O 0
1 O 0
. O 0
8 O 0
% O 0
- O 0
6 O 0
. O 0
1 O 0
% O 0
) O 0
than O 0
with O 0
HCTZ B-Chemical 0
monotherapies O 0
( O 0
7 O 0
. O 0
1 O 0
% O 0
- O 0
13 O 0
. O 0
3 O 0
% O 0
) O 0
. O 0

The O 0
majority O 0
of O 0
adverse O 0
events O 0
in O 0
the O 0
core O 0
study O 0
were O 0
of O 0
mild O 0
to O 0
moderate O 0
severity O 0
. O 0

The O 0
efficacy O 0
and O 0
tolerability O 0
of O 0
VAL B-Chemical 0
/ O 0
HCTZ B-Chemical 0
combinations O 0
were O 0
maintained O 0
during O 0
the O 0
extension O 0
( O 0
797 O 0
patients O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
this O 0
study O 0
population O 0
, O 0
combination O 0
therapies O 0
with O 0
VAL B-Chemical 0
/ O 0
HCTZ B-Chemical 0
were O 0
associated O 0
with O 0
significantly O 0
greater O 0
BP O 0
reductions O 0
compared O 0
with O 0
either O 0
monotherapy O 0
, O 0
were O 0
well O 0
tolerated O 0
, O 0
and O 0
were O 0
associated O 0
with O 0
less O 0
hypokalemia B-Disease 0
than O 0
HCTZ B-Chemical 0
alone O 0
. O 0

Succimer B-Chemical 0
chelation O 0
improves O 0
learning O 0
, O 0
attention O 0
, O 0
and O 0
arousal O 0
regulation O 0
in O 0
lead B-Chemical 0
- O 0
exposed O 0
rats O 0
but O 0
produces O 0
lasting O 0
cognitive B-Disease 0
impairment I-Disease 0
in O 0
the O 0
absence O 0
of O 0
lead B-Chemical 0
exposure O 0
. O 0

BACKGROUND O 0
: O 0
There O 0
is O 0
growing O 0
pressure O 0
for O 0
clinicians O 0
to O 0
prescribe O 0
chelation O 0
therapy O 0
at O 0
only O 0
slightly O 0
elevated O 0
blood O 0
lead B-Chemical 0
levels O 0
. O 0

However O 0
, O 0
very O 0
few O 0
studies O 0
have O 0
evaluated O 0
whether O 0
chelation O 0
improves O 0
cognitive O 0
outcomes O 0
in O 0
Pb B-Chemical 0
- O 0
exposed O 0
children O 0
, O 0
or O 0
whether O 0
these O 0
agents O 0
have O 0
adverse O 0
effects O 0
that O 0
may O 0
affect O 0
brain O 0
development O 0
in O 0
the O 0
absence O 0
of O 0
Pb B-Chemical 0
exposure O 0
. O 0

OBJECTIVES O 0
: O 0
The O 0
present O 0
study O 0
was O 0
designed O 0
to O 0
answer O 0
these O 0
questions O 0
, O 0
using O 0
a O 0
rodent O 0
model O 0
of O 0
early O 0
childhood O 0
Pb B-Chemical 0
exposure O 0
and O 0
treatment O 0
with O 0
succimer B-Chemical 0
, O 0
a O 0
widely O 0
used O 0
chelating O 0
agent O 0
for O 0
the O 0
treatment O 0
of O 0
Pb B-Disease 0
poisoning I-Disease 0
. O 0

RESULTS O 0
: O 0
Pb B-Chemical 0
exposure O 0
produced O 0
lasting O 0
impairments B-Disease 0
in I-Disease 0
learning I-Disease 0
, I-Disease 0
attention I-Disease 0
, I-Disease 0
inhibitory I-Disease 0
control I-Disease 0
, I-Disease 0
and I-Disease 0
arousal I-Disease 0
regulation I-Disease 0
, O 0
paralleling O 0
the O 0
areas O 0
of O 0
dysfunction O 0
seen O 0
in O 0
Pb B-Chemical 0
- O 0
exposed O 0
children O 0
. O 0

Succimer B-Chemical 0
treatment O 0
of O 0
the O 0
Pb B-Chemical 0
- O 0
exposed O 0
rats O 0
significantly O 0
improved O 0
learning O 0
, O 0
attention O 0
, O 0
and O 0
arousal O 0
regulation O 0
, O 0
although O 0
the O 0
efficacy O 0
of O 0
the O 0
treatment O 0
varied O 0
as O 0
a O 0
function O 0
of O 0
the O 0
Pb B-Chemical 0
exposure O 0
level O 0
and O 0
the O 0
specific O 0
functional O 0
deficit O 0
. O 0

In O 0
contrast O 0
, O 0
succimer B-Chemical 0
treatment O 0
of O 0
rats O 0
not O 0
previously O 0
exposed O 0
to O 0
Pb B-Chemical 0
produced O 0
lasting O 0
and O 0
pervasive O 0
cognitive B-Disease 0
and I-Disease 0
affective I-Disease 0
dysfunction I-Disease 0
comparable O 0
in O 0
magnitude O 0
to O 0
that O 0
produced O 0
by O 0
the O 0
higher O 0
Pb B-Chemical 0
exposure O 0
regimen O 0
. O 0

CONCLUSIONS O 0
: O 0
These O 0
are O 0
the O 0
first O 0
data O 0
, O 0
to O 0
our O 0
knowledge O 0
, O 0
to O 0
show O 0
that O 0
treatment O 0
with O 0
any O 0
chelating O 0
agent O 0
can O 0
alleviate O 0
cognitive B-Disease 0
deficits I-Disease 0
due O 0
to O 0
Pb B-Chemical 0
exposure O 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
it O 0
may O 0
be O 0
possible O 0
to O 0
identify O 0
a O 0
succimer B-Chemical 0
treatment O 0
protocol O 0
that O 0
improves O 0
cognitive O 0
outcomes O 0
in O 0
Pb B-Chemical 0
- O 0
exposed O 0
children O 0
. O 0

However O 0
, O 0
they O 0
also O 0
suggest O 0
that O 0
succimer B-Chemical 0
treatment O 0
should O 0
be O 0
strongly O 0
discouraged O 0
for O 0
children O 0
who O 0
do O 0
not O 0
have O 0
elevated O 0
tissue O 0
levels O 0
of O 0
Pb B-Chemical 0
or O 0
other O 0
heavy O 0
metals O 0
. O 0

Caffeine B-Chemical 0
challenge O 0
test O 0
in O 0
panic B-Disease 0
disorder I-Disease 0
and O 0
depression B-Disease 0
with O 0
panic B-Disease 0
attacks I-Disease 0
. O 0

Our O 0
aim O 0
was O 0
to O 0
observe O 0
if O 0
patients O 0
with O 0
panic B-Disease 0
disorder I-Disease 0
( O 0
PD B-Disease 0
) O 0
and O 0
patients O 0
with O 0
major B-Disease 0
depression I-Disease 0
with O 0
panic B-Disease 0
attacks I-Disease 0
( O 0
MDP B-Disease 0
) O 0
( O 0
Diagnostic O 0
and O 0
Statistical O 0
Manual O 0
of O 0
Mental B-Disease 0
Disorders I-Disease 0
, O 0
Fourth O 0
Edition O 0
criteria O 0
) O 0
respond O 0
in O 0
a O 0
similar O 0
way O 0
to O 0
the O 0
induction O 0
of O 0
panic B-Disease 0
attacks I-Disease 0
by O 0
an O 0
oral O 0
caffeine B-Chemical 0
challenge O 0
test O 0
. O 0

We O 0
randomly O 0
selected O 0
29 O 0
patients O 0
with O 0
PD B-Disease 0
, O 0
27 O 0
with O 0
MDP B-Disease 0
, O 0
25 O 0
with O 0
major B-Disease 0
depression I-Disease 0
without O 0
panic B-Disease 0
attacks I-Disease 0
( O 0
MD B-Disease 0
) O 0
, O 0
and O 0
28 O 0
healthy O 0
volunteers O 0
. O 0

The O 0
patients O 0
had O 0
no O 0
psychotropic O 0
drug O 0
for O 0
at O 0
least O 0
a O 0
4 O 0
- O 0
week O 0
period O 0
. O 0

In O 0
a O 0
randomized O 0
double O 0
- O 0
blind O 0
experiment O 0
performed O 0
in O 0
2 O 0
occasions O 0
7 O 0
days O 0
apart O 0
, O 0
480 O 0
mg O 0
caffeine B-Chemical 0
and O 0
a O 0
caffeine B-Chemical 0
- O 0
free O 0
( O 0
placebo O 0
) O 0
solution O 0
were O 0
administered O 0
in O 0
a O 0
coffee O 0
form O 0
and O 0
anxiety B-Disease 0
scales O 0
were O 0
applied O 0
before O 0
and O 0
after O 0
each O 0
test O 0
. O 0

A O 0
total O 0
of O 0
58 O 0
. O 0
6 O 0
% O 0
( O 0
n O 0
= O 0
17 O 0
) O 0
of O 0
patients O 0
with O 0
PD B-Disease 0
, O 0
44 O 0
. O 0
4 O 0
% O 0
( O 0
n O 0
= O 0
12 O 0
) O 0
of O 0
patients O 0
with O 0
MDP B-Disease 0
, O 0
12 O 0
. O 0
0 O 0
% O 0
( O 0
n O 0
= O 0
3 O 0
) O 0
of O 0
patients O 0
with O 0
MD B-Disease 0
, O 0
and O 0
7 O 0
. O 0
1 O 0
% O 0
( O 0
n O 0
= O 0
2 O 0
) O 0
of O 0
control O 0
subjects O 0
had O 0
a O 0
panic B-Disease 0
attack I-Disease 0
after O 0
the O 0
480 O 0
- O 0
mg O 0
caffeine B-Chemical 0
challenge O 0
test O 0
( O 0
chi O 0
( O 0
2 O 0
) O 0
( O 0
3 O 0
) O 0
= O 0
16 O 0
. O 0
22 O 0
, O 0
P O 0
= O 0
. O 0
001 O 0
) O 0
. O 0

The O 0
patients O 0
with O 0
PD B-Disease 0
and O 0
MDP B-Disease 0
were O 0
more O 0
sensitive O 0
to O 0
caffeine B-Chemical 0
than O 0
were O 0
patients O 0
with O 0
MD B-Disease 0
and O 0
healthy O 0
volunteers O 0
. O 0

No O 0
panic B-Disease 0
attack I-Disease 0
was O 0
observed O 0
after O 0
the O 0
caffeine B-Chemical 0
- O 0
free O 0
solution O 0
intake O 0
. O 0

The O 0
patients O 0
with O 0
MD B-Disease 0
had O 0
a O 0
lower O 0
heart O 0
rate O 0
response O 0
to O 0
the O 0
test O 0
than O 0
all O 0
the O 0
other O 0
groups O 0
( O 0
2 O 0
- O 0
way O 0
analysis O 0
of O 0
variance O 0
, O 0
group O 0
by O 0
time O 0
interaction O 0
with O 0
Greenhouse O 0
- O 0
Geisser O 0
correction O 0
: O 0
F O 0
( O 0
3 O 0
, O 0
762 O 0
) O 0
= O 0
2 O 0
. O 0
85 O 0
, O 0
P O 0
= O 0
. O 0
026 O 0
) O 0
. O 0

Our O 0
data O 0
suggest O 0
that O 0
there O 0
is O 0
an O 0
association O 0
between O 0
panic B-Disease 0
attacks I-Disease 0
, O 0
no O 0
matter O 0
if O 0
associated O 0
with O 0
PD B-Disease 0
or O 0
MDP B-Disease 0
, O 0
and O 0
hyperreactivity O 0
to O 0
an O 0
oral O 0
caffeine B-Chemical 0
challenge O 0
test O 0
. O 0

Mitral O 0
annuloplasty O 0
as O 0
a O 0
ventricular O 0
restoration O 0
method O 0
for O 0
the O 0
failing B-Disease 0
left I-Disease 0
ventricle I-Disease 0
: O 0
a O 0
pilot O 0
study O 0
. O 0

BACKGROUND O 0
AND O 0
AIM O 0
OF O 0
THE O 0
STUDY O 0
: O 0
Undersized O 0
mitral O 0
annuloplasty O 0
( O 0
MAP O 0
) O 0
is O 0
effective O 0
in O 0
patients O 0
with O 0
dilated B-Disease 0
cardiomyopathy I-Disease 0
and O 0
functional O 0
mitral B-Disease 0
regurgitation I-Disease 0
( O 0
MR B-Disease 0
) O 0
since O 0
, O 0
as O 0
well O 0
as O 0
addressing O 0
the O 0
MR B-Disease 0
, O 0
the O 0
MAP O 0
may O 0
also O 0
reshape O 0
the O 0
dilated O 0
left O 0
ventricular O 0
( O 0
LV O 0
) O 0
base O 0
. O 0

However O 0
, O 0
the O 0
direct O 0
benefits O 0
of O 0
this O 0
possible O 0
reshaping O 0
on O 0
LV O 0
function O 0
in O 0
the O 0
absence O 0
of O 0
underlying O 0
MR B-Disease 0
remain O 0
incompletely O 0
understood O 0
. O 0

The O 0
study O 0
aim O 0
was O 0
to O 0
identify O 0
these O 0
benefits O 0
in O 0
a O 0
canine O 0
model O 0
of O 0
acute O 0
heart B-Disease 0
failure I-Disease 0
. O 0

METHODS O 0
: O 0
Six O 0
dogs O 0
underwent O 0
MAP O 0
with O 0
a O 0
prosthetic O 0
band O 0
on O 0
the O 0
posterior O 0
mitral O 0
annulus O 0
, O 0
using O 0
four O 0
mattress O 0
sutures O 0
. O 0

The O 0
sutures O 0
were O 0
passed O 0
individually O 0
through O 0
four O 0
tourniquets O 0
and O 0
exteriorized O 0
untied O 0
via O 0
the O 0
left O 0
atriotomy O 0
. O 0

Sonomicrometry O 0
crystals O 0
were O 0
implanted O 0
around O 0
the O 0
mitral O 0
annulus O 0
and O 0
left O 0
ventricle O 0
to O 0
measure O 0
geometry O 0
and O 0
regional O 0
function O 0
. O 0

Acute O 0
heart B-Disease 0
failure I-Disease 0
was O 0
induced O 0
by O 0
propranolol B-Chemical 0
and O 0
volume O 0
loading O 0
after O 0
weaning O 0
from O 0
cardiopulmonary O 0
bypass O 0
; O 0
an O 0
absence O 0
of O 0
MR B-Disease 0
was O 0
confirmed O 0
by O 0
echocardiography O 0
. O 0

MAP O 0
was O 0
accomplished O 0
by O 0
cinching O 0
the O 0
tourniquets O 0
. O 0

Data O 0
were O 0
acquired O 0
at O 0
baseline O 0
, O 0
after O 0
induction O 0
of O 0
acute O 0
heart B-Disease 0
failure I-Disease 0
, O 0
and O 0
after O 0
MAP O 0
. O 0

RESULTS O 0
: O 0
MAP O 0
decreased O 0
mitral O 0
annular O 0
dimensions O 0
in O 0
both O 0
commissure O 0
- O 0
commissure O 0
and O 0
septal O 0
- O 0
lateral O 0
directions O 0
. O 0

Concomitantly O 0
, O 0
the O 0
diastolic O 0
diameter O 0
of O 0
the O 0
LV O 0
base O 0
and O 0
LV O 0
sphericity O 0
decreased O 0
( O 0
i O 0
. O 0
e O 0
. O 0
, O 0
improved O 0
) O 0
from O 0
37 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
9 O 0
. O 0
3 O 0
to O 0
35 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
10 O 0
mm O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
063 O 0
) O 0
, O 0
and O 0
from O 0
67 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
18 O 0
. O 0
6 O 0
% O 0
to O 0
65 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
18 O 0
. O 0
9 O 0
% O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
016 O 0
) O 0
, O 0
respectively O 0
. O 0

Decreases O 0
were O 0
evident O 0
in O 0
both O 0
LV O 0
end O 0
- O 0
diastolic O 0
pressure O 0
( O 0
from O 0
17 O 0
+ O 0
/ O 0
- O 0
7 O 0
to O 0
15 O 0
+ O 0
/ O 0
- O 0
6 O 0
mmHg O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
0480 O 0
and O 0
Tau O 0
( O 0
from O 0
48 O 0
+ O 0
/ O 0
- O 0
8 O 0
to O 0
45 O 0
+ O 0
/ O 0
- O 0
8 O 0
ms O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
, O 0
while O 0
fractional O 0
shortening O 0
at O 0
the O 0
LV O 0
base O 0
increased O 0
from O 0
7 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
5 O 0
% O 0
to O 0
9 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
5 O 0
% O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
045 O 0
) O 0
. O 0

After O 0
MAP O 0
, O 0
increases O 0
were O 0
identified O 0
in O 0
both O 0
cardiac O 0
output O 0
( O 0
from O 0
1 O 0
. O 0
54 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
57 O 0
to O 0
1 O 0
. O 0
65 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
57 O 0
1 O 0
/ O 0
min O 0
) O 0
and O 0
Emax O 0
( O 0
from O 0
1 O 0
. O 0
86 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
9 O 0
to O 0
2 O 0
. O 0
41 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
31 O 0
mmHg O 0
/ O 0
ml O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
data O 0
acquired O 0
suggest O 0
that O 0
isolated O 0
MAP O 0
may O 0
have O 0
certain O 0
benefits O 0
on O 0
LV O 0
dimension O 0
/ O 0
function O 0
in O 0
acute O 0
heart B-Disease 0
failure I-Disease 0
, O 0
even O 0
in O 0
the O 0
absence O 0
of O 0
MR B-Disease 0
. O 0

However O 0
, O 0
further O 0
investigations O 0
are O 0
warranted O 0
in O 0
a O 0
model O 0
of O 0
chronic O 0
heart B-Disease 0
failure I-Disease 0
. O 0

Piperacillin B-Chemical 0
/ I-Chemical 0
tazobactam I-Chemical 0
- O 0
induced O 0
seizure B-Disease 0
rapidly O 0
reversed O 0
by O 0
high O 0
flux O 0
hemodialysis O 0
in O 0
a O 0
patient O 0
on O 0
peritoneal O 0
dialysis O 0
. O 0

Despite O 0
popular O 0
use O 0
of O 0
piperacillin B-Chemical 0
, O 0
the O 0
dire O 0
neurotoxicity B-Disease 0
associated O 0
with O 0
piperacillin B-Chemical 0
still O 0
goes O 0
unrecognized O 0
, O 0
leading O 0
to O 0
a O 0
delay O 0
in O 0
appropriate O 0
management O 0
. O 0

We O 0
report O 0
a O 0
57 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
renal I-Disease 0
disease I-Disease 0
receiving O 0
continuous O 0
ambulatory O 0
peritoneal O 0
dialysis O 0
( O 0
CAPD O 0
) O 0
, O 0
who O 0
developed O 0
slurred O 0
speech O 0
, O 0
tremor B-Disease 0
, O 0
bizarre O 0
behavior O 0
, O 0
progressive O 0
mental O 0
confusion B-Disease 0
, O 0
and O 0
2 O 0
episodes O 0
of O 0
generalized O 0
tonic B-Disease 0
- I-Disease 0
clonic I-Disease 0
seizure I-Disease 0
( O 0
GTCS B-Disease 0
) O 0
after O 0
5 O 0
doses O 0
of O 0
piperacillin B-Chemical 0
/ I-Chemical 0
tazobactam I-Chemical 0
( O 0
2 O 0
g O 0
/ O 0
250 O 0
mg O 0
) O 0
were O 0
given O 0
for O 0
bronchiectasis B-Disease 0
with O 0
secondary B-Disease 0
infection I-Disease 0
. O 0

The O 0
laboratory O 0
data O 0
revealed O 0
normal O 0
plasma O 0
electrolyte O 0
and O 0
ammonia B-Chemical 0
levels O 0
but O 0
leukocytosis B-Disease 0
. O 0

Neurologic O 0
examinations O 0
showed O 0
dysarthria B-Disease 0
and O 0
bilateral O 0
Babinski O 0
sign O 0
. O 0

Computed O 0
tomography O 0
of O 0
brain O 0
and O 0
electroencephalogram O 0
were O 0
unremarkable O 0
. O 0

Despite O 0
the O 0
use O 0
of O 0
antiepileptic O 0
agents O 0
, O 0
another O 0
GTCS B-Disease 0
episode O 0
recurred O 0
after O 0
the O 0
sixth O 0
dose O 0
of O 0
piperacillin B-Chemical 0
/ I-Chemical 0
tazobactam I-Chemical 0
. O 0

Brain O 0
magnetic O 0
resonance O 0
imaging O 0
did O 0
not O 0
demonstrate O 0
acute O 0
infarction B-Disease 0
and O 0
organic B-Disease 0
brain I-Disease 0
lesions I-Disease 0
. O 0

Initiation O 0
of O 0
high O 0
- O 0
flux O 0
hemodialysis O 0
rapidly O 0
reversed O 0
the O 0
neurologic O 0
symptoms O 0
within O 0
4 O 0
hours O 0
. O 0

Piperacillin B-Chemical 0
- O 0
induced O 0
encephalopathy B-Disease 0
should O 0
be O 0
considered O 0
in O 0
any O 0
uremic B-Disease 0
patients O 0
with O 0
unexplained O 0
neurological O 0
manifestations O 0
. O 0

CAPD O 0
is O 0
inefficient O 0
in O 0
removing O 0
piperacillin B-Chemical 0
, O 0
whereas O 0
hemodialysis O 0
can O 0
rapidly O 0
terminate O 0
the O 0
piperacillin B-Chemical 0
- O 0
induced O 0
encephalopathy B-Disease 0
. O 0

Frequency O 0
of O 0
transient O 0
ipsilateral O 0
vocal B-Disease 0
cord I-Disease 0
paralysis I-Disease 0
in O 0
patients O 0
undergoing O 0
carotid O 0
endarterectomy O 0
under O 0
local O 0
anesthesia O 0
. O 0

BACKGROUND O 0
: O 0
Especially O 0
because O 0
of O 0
improvements O 0
in O 0
clinical O 0
neurologic O 0
monitoring O 0
, O 0
carotid O 0
endarterectomy O 0
done O 0
under O 0
local O 0
anesthesia O 0
has O 0
become O 0
the O 0
technique O 0
of O 0
choice O 0
in O 0
several O 0
centers O 0
. O 0

Temporary O 0
ipsilateral O 0
vocal B-Disease 0
nerve I-Disease 0
palsies I-Disease 0
due O 0
to O 0
local O 0
anesthetics O 0
have O 0
been O 0
described O 0
, O 0
however O 0
. O 0

Such O 0
complications O 0
are O 0
most O 0
important O 0
in O 0
situations O 0
where O 0
there O 0
is O 0
a O 0
pre O 0
- O 0
existing O 0
contralateral O 0
paralysis B-Disease 0
. O 0

We O 0
therefore O 0
examined O 0
the O 0
effect O 0
of O 0
local O 0
anesthesia O 0
on O 0
vocal O 0
cord O 0
function O 0
to O 0
better O 0
understand O 0
its O 0
possible O 0
consequences O 0
. O 0

METHODS O 0
: O 0
This O 0
prospective O 0
study O 0
included O 0
28 O 0
patients O 0
undergoing O 0
carotid O 0
endarterectomy O 0
under O 0
local O 0
anesthesia O 0
. O 0

Vocal O 0
cord O 0
function O 0
was O 0
evaluated O 0
before O 0
, O 0
during O 0
, O 0
and O 0
after O 0
surgery O 0
( O 0
postoperative O 0
day O 0
1 O 0
) O 0
using O 0
flexible O 0
laryngoscopy O 0
. O 0

Anesthesia O 0
was O 0
performed O 0
by O 0
injecting O 0
20 O 0
to O 0
40 O 0
mL O 0
of O 0
a O 0
mixture O 0
of O 0
long O 0
- O 0
acting O 0
( O 0
ropivacaine B-Chemical 0
) O 0
and O 0
short O 0
- O 0
acting O 0
( O 0
prilocaine B-Chemical 0
) O 0
anesthetic O 0
. O 0

RESULTS O 0
: O 0
All O 0
patients O 0
had O 0
normal O 0
vocal O 0
cord O 0
function O 0
preoperatively O 0
. O 0

Twelve O 0
patients O 0
( O 0
43 O 0
% O 0
) O 0
were O 0
found O 0
to O 0
have O 0
intraoperative O 0
ipsilateral O 0
vocal B-Disease 0
cord I-Disease 0
paralysis I-Disease 0
. O 0

It O 0
resolved O 0
in O 0
all O 0
cases O 0
< O 0
or O 0
= O 0
24 O 0
hours O 0
. O 0

There O 0
were O 0
no O 0
significant O 0
differences O 0
in O 0
operating O 0
time O 0
or O 0
volume O 0
or O 0
frequency O 0
of O 0
anesthetic O 0
administration O 0
in O 0
patients O 0
with O 0
temporary O 0
vocal B-Disease 0
cord I-Disease 0
paralysis I-Disease 0
compared O 0
with O 0
those O 0
without O 0
. O 0

CONCLUSION O 0
: O 0
Local O 0
anesthesia O 0
led O 0
to O 0
temporary O 0
ipsilateral O 0
vocal B-Disease 0
cord I-Disease 0
paralysis I-Disease 0
in O 0
almost O 0
half O 0
of O 0
these O 0
patients O 0
. O 0

Because O 0
pre O 0
- O 0
existing O 0
paralysis B-Disease 0
is O 0
of O 0
a O 0
relevant O 0
frequency O 0
( O 0
up O 0
to O 0
3 O 0
% O 0
) O 0
, O 0
a O 0
preoperative O 0
evaluation O 0
of O 0
vocal O 0
cord O 0
function O 0
before O 0
carotid O 0
endarterectomy O 0
under O 0
local O 0
anesthesia O 0
is O 0
recommended O 0
to O 0
avoid O 0
intraoperative O 0
bilateral O 0
paralysis B-Disease 0
. O 0

In O 0
patients O 0
with O 0
preoperative O 0
contralateral O 0
vocal B-Disease 0
cord I-Disease 0
paralysis I-Disease 0
, O 0
surgery O 0
under O 0
general O 0
anesthesia O 0
should O 0
be O 0
considered O 0
. O 0

Impaired B-Disease 0
fear I-Disease 0
recognition I-Disease 0
in O 0
regular O 0
recreational O 0
cocaine B-Chemical 0
users O 0
. O 0

INTRODUCTION O 0
: O 0
The O 0
ability O 0
to O 0
read O 0
facial O 0
expressions O 0
is O 0
essential O 0
for O 0
normal O 0
human O 0
social O 0
interaction O 0
. O 0

The O 0
aim O 0
of O 0
the O 0
present O 0
study O 0
was O 0
to O 0
conduct O 0
the O 0
first O 0
investigation O 0
of O 0
facial O 0
expression O 0
recognition O 0
performance O 0
in O 0
recreational O 0
cocaine B-Chemical 0
users O 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
Three O 0
groups O 0
, O 0
comprised O 0
of O 0
21 O 0
cocaine B-Chemical 0
naive O 0
participants O 0
( O 0
CN O 0
) O 0
, O 0
30 O 0
occasional O 0
cocaine B-Chemical 0
( O 0
OC O 0
) O 0
, O 0
and O 0
48 O 0
regular O 0
recreational O 0
cocaine B-Chemical 0
( O 0
RC O 0
) O 0
users O 0
, O 0
were O 0
compared O 0
. O 0

An O 0
emotional O 0
facial O 0
expression O 0
( O 0
EFE O 0
) O 0
task O 0
consisting O 0
of O 0
a O 0
male O 0
and O 0
female O 0
face O 0
expressing O 0
six O 0
basic O 0
emotions O 0
( O 0
happiness O 0
, O 0
surprise O 0
, O 0
sadness O 0
, O 0
anger O 0
, O 0
fear O 0
, O 0
and O 0
disgust O 0
) O 0
was O 0
administered O 0
. O 0

Mean O 0
percent O 0
accuracy O 0
and O 0
latencies O 0
for O 0
correct O 0
responses O 0
across O 0
eight O 0
presentations O 0
of O 0
each O 0
basic O 0
emotion O 0
were O 0
derived O 0
. O 0

Participants O 0
were O 0
also O 0
assessed O 0
with O 0
the O 0
" O 0
Eyes O 0
task O 0
" O 0
to O 0
investigate O 0
their O 0
ability O 0
to O 0
recognize O 0
more O 0
complex O 0
emotional O 0
states O 0
and O 0
the O 0
Symptom O 0
CheckList O 0
- O 0
90 O 0
- O 0
Revised O 0
to O 0
measure O 0
psychopathology O 0
. O 0

RESULTS O 0
: O 0
There O 0
were O 0
no O 0
group O 0
differences O 0
in O 0
psychopathology O 0
or O 0
" O 0
eyes O 0
task O 0
" O 0
performance O 0
, O 0
but O 0
the O 0
RC O 0
group O 0
, O 0
who O 0
otherwise O 0
had O 0
similar O 0
illicit O 0
substance O 0
use O 0
histories O 0
to O 0
the O 0
OC O 0
group O 0
, O 0
exhibited O 0
impaired B-Disease 0
fear I-Disease 0
recognition I-Disease 0
accuracy O 0
compared O 0
to O 0
the O 0
OC O 0
and O 0
CN O 0
groups O 0
. O 0

The O 0
RC O 0
group O 0
also O 0
correctly O 0
identified O 0
anger O 0
, O 0
fear O 0
, O 0
happiness O 0
, O 0
and O 0
surprise O 0
, O 0
more O 0
slowly O 0
than O 0
CN O 0
, O 0
but O 0
not O 0
OC O 0
participants O 0
. O 0

The O 0
OC O 0
group O 0
was O 0
slower O 0
than O 0
CN O 0
when O 0
correctly O 0
identifying O 0
disgust O 0
. O 0

The O 0
selective O 0
deficit B-Disease 0
in I-Disease 0
fear I-Disease 0
recognition I-Disease 0
accuracy O 0
manifested O 0
by O 0
the O 0
RC O 0
group O 0
cannot O 0
be O 0
explained O 0
by O 0
the O 0
subacute O 0
effects O 0
of O 0
cocaine B-Chemical 0
, O 0
or O 0
ecstasy B-Chemical 0
, O 0
because O 0
recent O 0
and O 0
less O 0
recent O 0
users O 0
of O 0
these O 0
drugs O 0
within O 0
this O 0
group O 0
were O 0
similarly O 0
impaired O 0
. O 0

Possible O 0
parallels O 0
between O 0
RC O 0
users O 0
and O 0
psychopaths B-Disease 0
with O 0
respect O 0
to O 0
impaired B-Disease 0
fear I-Disease 0
recognition I-Disease 0
, O 0
amygdala B-Disease 0
dysfunction I-Disease 0
, O 0
and O 0
etiology O 0
are O 0
discussed O 0
. O 0

Damage B-Disease 0
of I-Disease 0
substantia I-Disease 0
nigra I-Disease 0
pars I-Disease 0
reticulata I-Disease 0
during O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
status B-Disease 0
epilepticus I-Disease 0
in O 0
the O 0
rat O 0
: O 0
immunohistochemical O 0
study O 0
of O 0
neurons O 0
, O 0
astrocytes O 0
and O 0
serum O 0
- O 0
protein O 0
extravasation O 0
. O 0

The O 0
substantia O 0
nigra O 0
has O 0
a O 0
gating O 0
function O 0
controlling O 0
the O 0
spread O 0
of O 0
epileptic B-Disease 0
seizure I-Disease 0
activity O 0
. O 0

Additionally O 0
, O 0
in O 0
models O 0
of O 0
prolonged B-Disease 0
status I-Disease 0
epilepticus I-Disease 0
the O 0
pars O 0
reticulata O 0
of O 0
substantia O 0
nigra O 0
( O 0
SNR O 0
) O 0
suffers O 0
from O 0
a O 0
massive O 0
lesion O 0
which O 0
may O 0
arise O 0
from O 0
a O 0
massive O 0
metabolic B-Disease 0
derangement I-Disease 0
and O 0
hyperexcitation O 0
developing O 0
in O 0
the O 0
activated O 0
SNR O 0
. O 0

In O 0
this O 0
study O 0
, O 0
status B-Disease 0
epilepticus I-Disease 0
was O 0
induced O 0
by O 0
systemic O 0
injection O 0
of O 0
pilocarpine B-Chemical 0
in O 0
rats O 0
. O 0

The O 0
neuropathology O 0
of O 0
SNR O 0
was O 0
investigated O 0
using O 0
immunohistochemical O 0
techniques O 0
with O 0
the O 0
major O 0
emphasis O 0
on O 0
the O 0
time O 0
- O 0
course O 0
of O 0
changes O 0
in O 0
neurons O 0
and O 0
astrocytes O 0
. O 0

Animals O 0
surviving O 0
20 O 0
, O 0
30 O 0
, O 0
40 O 0
, O 0
60 O 0
min O 0
, O 0
2 O 0
, O 0
3 O 0
, O 0
6 O 0
hours O 0
, O 0
1 O 0
, O 0
2 O 0
, O 0
and O 0
3 O 0
days O 0
after O 0
induction O 0
of O 0
status B-Disease 0
epilepticus I-Disease 0
were O 0
perfusion O 0
- O 0
fixed O 0
, O 0
and O 0
brains O 0
processed O 0
for O 0
immunohistochemical O 0
staining O 0
of O 0
SNR O 0
. O 0

Nissl O 0
- O 0
staining O 0
and O 0
antibodies O 0
against O 0
the O 0
neuron O 0
- O 0
specific O 0
calcium B-Chemical 0
- O 0
binding O 0
protein O 0
, O 0
parvalbumin O 0
, O 0
served O 0
to O 0
detect O 0
neuronal B-Disease 0
damage I-Disease 0
in O 0
SNR O 0
. O 0

Antibodies O 0
against O 0
the O 0
astroglia O 0
- O 0
specific O 0
cytoskeletal O 0
protein O 0
, O 0
glial O 0
fibrillary O 0
acidic O 0
protein O 0
( O 0
GFAP O 0
) O 0
, O 0
and O 0
against O 0
the O 0
glial O 0
calcium B-Chemical 0
- O 0
binding O 0
protein O 0
, O 0
S O 0
- O 0
100 O 0
protein O 0
, O 0
were O 0
used O 0
to O 0
assess O 0
the O 0
status O 0
of O 0
astrocytes O 0
. O 0

Immunohistochemical O 0
staining O 0
for O 0
serum O 0
- O 0
albumin O 0
and O 0
immunoglobulins O 0
in O 0
brain O 0
tissue O 0
was O 0
taken O 0
as O 0
indicator O 0
of O 0
blood O 0
- O 0
brain O 0
barrier O 0
disturbances O 0
and O 0
vasogenic B-Disease 0
edema I-Disease 0
formation O 0
. O 0

Immunohistochemical O 0
staining O 0
indicated O 0
loss O 0
of O 0
GFAP O 0
- O 0
staining O 0
already O 0
at O 0
30 O 0
min O 0
after O 0
induction O 0
of O 0
seizures B-Disease 0
in O 0
an O 0
oval O 0
focus O 0
situated O 0
in O 0
the O 0
center O 0
of O 0
SNR O 0
while O 0
sparing O 0
medial O 0
and O 0
lateral O 0
aspects O 0
. O 0

At O 0
1 O 0
h O 0
there O 0
was O 0
additional O 0
vacuolation O 0
in O 0
S O 0
- O 0
100 O 0
protein O 0
staining O 0
. O 0

By O 0
2 O 0
hours O 0
, O 0
parvalbumin O 0
- O 0
staining O 0
changed O 0
in O 0
the O 0
central O 0
SNR O 0
indicating O 0
neuronal B-Disease 0
damage I-Disease 0
, O 0
and O 0
Nissl O 0
- O 0
staining O 0
visualized O 0
some O 0
neuronal O 0
distortion O 0
. O 0

Staining O 0
for O 0
serum O 0
- O 0
proteins O 0
occurred O 0
in O 0
a O 0
patchy O 0
manner O 0
throughout O 0
the O 0
forebrain O 0
during O 0
the O 0
first O 0
hours O 0
. O 0

By O 0
6 O 0
h O 0
, O 0
vasogenic B-Disease 0
edema I-Disease 0
covered O 0
the O 0
lesioned B-Disease 0
SNR I-Disease 0
. O 0

By O 0
24 O 0
h O 0
, O 0
glial O 0
and O 0
neuronal O 0
markers O 0
indicated O 0
a O 0
massive O 0
lesion O 0
in O 0
the O 0
center O 0
of O 0
SNR O 0
. O 0

By O 0
48 O 0
- O 0
72 O 0
h O 0
, O 0
astrocytes O 0
surrounding O 0
the O 0
lesion O 0
increased O 0
in O 0
size O 0
, O 0
and O 0
polymorphic O 0
phagocytotic O 0
cells O 0
invaded O 0
the O 0
damaged O 0
area O 0
. O 0

In O 0
a O 0
further O 0
group O 0
of O 0
animals O 0
surviving O 0
1 O 0
to O 0
5 O 0
days O 0
, O 0
conventional O 0
paraffin O 0
- O 0
sections O 0
confirmed O 0
the O 0
neuronal O 0
and O 0
glial O 0
damage B-Disease 0
of I-Disease 0
SNR I-Disease 0
. O 0

Additional O 0
pathology O 0
of O 0
similar O 0
quality O 0
was O 0
found O 0
in O 0
the O 0
globus O 0
pallidus O 0
. O 0

Since O 0
astrocytes O 0
were O 0
always O 0
damaged O 0
in O 0
parallel O 0
with O 0
neurons O 0
in O 0
SNR O 0
it O 0
is O 0
proposed O 0
that O 0
the O 0
anatomical O 0
and O 0
functional O 0
interrelationship O 0
between O 0
neurons O 0
and O 0
astrocytes O 0
is O 0
particularly O 0
tight O 0
in O 0
SNR O 0
. O 0

Both O 0
cell O 0
elements O 0
may O 0
suffer O 0
in O 0
common O 0
from O 0
metabolic O 0
disturbance O 0
and O 0
neurotransmitter B-Disease 0
dysfunction I-Disease 0
as O 0
occur O 0
during O 0
massive O 0
status B-Disease 0
epilepticus I-Disease 0
. O 0

Neuroprotective O 0
effects O 0
of O 0
melatonin B-Chemical 0
upon O 0
the O 0
offspring O 0
cerebellar O 0
cortex O 0
in O 0
the O 0
rat O 0
model O 0
of O 0
BCNU B-Chemical 0
- O 0
induced O 0
cortical B-Disease 0
dysplasia I-Disease 0
. O 0

Cortical B-Disease 0
dysplasia I-Disease 0
is O 0
a O 0
malformation O 0
characterized O 0
by O 0
defects O 0
in O 0
proliferation O 0
, O 0
migration O 0
and O 0
maturation O 0
. O 0

This O 0
study O 0
was O 0
designed O 0
to O 0
evaluate O 0
the O 0
alterations O 0
in O 0
offspring O 0
rat O 0
cerebellum O 0
induced O 0
by O 0
maternal O 0
exposure O 0
to O 0
carmustine B-Chemical 0
- O 0
[ O 0
1 B-Chemical 0
, I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
bis I-Chemical 0
( I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
chloroethyl I-Chemical 0
) I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
nitrosoure I-Chemical 0
] O 0
( O 0
BCNU B-Chemical 0
) O 0
and O 0
to O 0
investigate O 0
the O 0
effects O 0
of O 0
exogenous O 0
melatonin B-Chemical 0
upon O 0
cerebellar O 0
BCNU B-Chemical 0
- O 0
induced O 0
cortical B-Disease 0
dysplasia I-Disease 0
, O 0
using O 0
histological O 0
and O 0
biochemical O 0
analyses O 0
. O 0

Pregnant O 0
Wistar O 0
rats O 0
were O 0
assigned O 0
to O 0
five O 0
groups O 0
: O 0
intact O 0
- O 0
control O 0
, O 0
saline O 0
- O 0
control O 0
, O 0
melatonin B-Chemical 0
- O 0
treated O 0
, O 0
BCNU B-Chemical 0
- O 0
exposed O 0
and O 0
BCNU B-Chemical 0
- O 0
exposed O 0
plus O 0
melatonin B-Chemical 0
. O 0

Rats O 0
were O 0
exposed O 0
to O 0
BCNU B-Chemical 0
on O 0
embryonic O 0
day O 0
15 O 0
and O 0
melatonin B-Chemical 0
was O 0
given O 0
until O 0
delivery O 0
. O 0

Immuno O 0
/ O 0
histochemistry O 0
and O 0
electron O 0
microscopy O 0
were O 0
carried O 0
out O 0
on O 0
the O 0
offspring O 0
cerebellum O 0
, O 0
and O 0
levels O 0
of O 0
malondialdehyde B-Chemical 0
and O 0
superoxide B-Chemical 0
dismutase O 0
were O 0
determined O 0
. O 0

Histopathologically O 0
, O 0
typical O 0
findings O 0
were O 0
observed O 0
in O 0
the O 0
cerebella O 0
from O 0
the O 0
control O 0
groups O 0
, O 0
but O 0
the O 0
findings O 0
consistent O 0
with O 0
early O 0
embryonic O 0
development O 0
were O 0
noted O 0
in O 0
BCNU B-Chemical 0
- O 0
exposed O 0
cortical B-Disease 0
dysplasia I-Disease 0
group O 0
. O 0

There O 0
was O 0
a O 0
marked O 0
increase O 0
in O 0
the O 0
number O 0
of O 0
TUNEL O 0
positive O 0
cells O 0
and O 0
nestin O 0
positive O 0
cells O 0
in O 0
BCNU B-Chemical 0
- O 0
exposed O 0
group O 0
, O 0
but O 0
a O 0
decreased O 0
immunoreactivity O 0
to O 0
glial O 0
fibrillary O 0
acidic O 0
protein O 0
, O 0
synaptophysin O 0
and O 0
transforming O 0
growth O 0
factor O 0
beta1 O 0
was O 0
observed O 0
, O 0
indicating O 0
a O 0
delayed O 0
maturation O 0
, O 0
and O 0
melatonin B-Chemical 0
significantly O 0
reversed O 0
these O 0
changes O 0
. O 0

Malondialdehyde B-Chemical 0
level O 0
in O 0
BCNU B-Chemical 0
- O 0
exposed O 0
group O 0
was O 0
higher O 0
than O 0
those O 0
in O 0
control O 0
groups O 0
and O 0
melatonin B-Chemical 0
decreased O 0
malondialdehyde B-Chemical 0
levels O 0
in O 0
BCNU B-Chemical 0
group O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
, O 0
while O 0
there O 0
were O 0
no O 0
significant O 0
differences O 0
in O 0
the O 0
superoxide B-Chemical 0
dismutase O 0
levels O 0
between O 0
these O 0
groups O 0
. O 0

These O 0
data O 0
suggest O 0
that O 0
exposure O 0
of O 0
animals O 0
to O 0
BCNU B-Chemical 0
during O 0
pregnancy O 0
leads O 0
to O 0
delayed O 0
maturation O 0
of O 0
offspring O 0
cerebellum O 0
and O 0
melatonin B-Chemical 0
protects O 0
the O 0
cerebellum O 0
against O 0
the O 0
effects O 0
of O 0
BCNU B-Chemical 0
. O 0

Reduced O 0
cardiotoxicity B-Disease 0
of O 0
doxorubicin B-Chemical 0
given O 0
in O 0
the O 0
form O 0
of O 0
N B-Chemical 0
- I-Chemical 0
( I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
hydroxypropyl I-Chemical 0
) I-Chemical 0
methacrylamide I-Chemical 0
conjugates O 0
: O 0
and O 0
experimental O 0
study O 0
in O 0
the O 0
rat O 0
. O 0

A O 0
rat O 0
model O 0
was O 0
used O 0
to O 0
evaluate O 0
the O 0
general O 0
acute O 0
toxicity B-Disease 0
and O 0
the O 0
late O 0
cardiotoxicity B-Disease 0
of O 0
4 O 0
mg O 0
/ O 0
kg O 0
doxorubicin B-Chemical 0
( O 0
DOX B-Chemical 0
) O 0
given O 0
either O 0
as O 0
free O 0
drug O 0
or O 0
in O 0
the O 0
form O 0
of O 0
three O 0
N B-Chemical 0
- I-Chemical 0
( I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
hydroxypropyl I-Chemical 0
) I-Chemical 0
methacrylamide I-Chemical 0
( O 0
HPMA B-Chemical 0
) O 0
copolymer O 0
conjugates O 0
. O 0

In O 0
these O 0
HPMA B-Chemical 0
copolymers O 0
, O 0
DOX B-Chemical 0
was O 0
covalently O 0
bound O 0
via O 0
peptide O 0
linkages O 0
that O 0
were O 0
either O 0
non O 0
- O 0
biodegradable O 0
( O 0
Gly O 0
- O 0
Gly O 0
) O 0
or O 0
degradable O 0
by O 0
lysosomal O 0
proteinases O 0
( O 0
Gly B-Chemical 0
- I-Chemical 0
Phe I-Chemical 0
- I-Chemical 0
Leu I-Chemical 0
- I-Chemical 0
Gly I-Chemical 0
) O 0
. O 0

In O 0
addition O 0
, O 0
one O 0
biodegradable O 0
conjugate O 0
containing O 0
galactosamine B-Chemical 0
was O 0
used O 0
; O 0
this O 0
residue O 0
was O 0
targeted O 0
to O 0
the O 0
liver O 0
. O 0

Over O 0
the O 0
first O 0
3 O 0
weeks O 0
after O 0
the O 0
i O 0
. O 0
v O 0
. O 0
administration O 0
of O 0
free O 0
and O 0
polymer O 0
- O 0
bound O 0
DOX B-Chemical 0
, O 0
all O 0
animals O 0
showed O 0
a O 0
transient O 0
reduction O 0
in O 0
body O 0
weight O 0
. O 0

However O 0
, O 0
the O 0
maximal O 0
reduction O 0
in O 0
body O 0
weight O 0
seen O 0
in O 0
animals O 0
that O 0
received O 0
polymer O 0
- O 0
bound O 0
DOX B-Chemical 0
( O 0
4 O 0
mg O 0
/ O 0
kg O 0
) O 0
was O 0
significantly O 0
lower O 0
than O 0
that O 0
observed O 0
in O 0
those O 0
that O 0
received O 0
free O 0
DOX B-Chemical 0
( O 0
4 O 0
mg O 0
/ O 0
kg O 0
) O 0
or O 0
a O 0
mixture O 0
of O 0
the O 0
unmodified O 0
parent O 0
HPMA B-Chemical 0
copolymer O 0
and O 0
free O 0
DOX B-Chemical 0
( O 0
4 O 0
mg O 0
/ O 0
kg O 0
; O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Throughout O 0
the O 0
study O 0
( O 0
20 O 0
weeks O 0
) O 0
, O 0
deaths O 0
related O 0
to O 0
cardiotoxicity B-Disease 0
were O 0
observed O 0
only O 0
in O 0
animals O 0
that O 0
received O 0
either O 0
free O 0
DOX B-Chemical 0
or O 0
the O 0
mixture O 0
of O 0
HPMA B-Chemical 0
copolymer O 0
and O 0
free O 0
DOX B-Chemical 0
; O 0
in O 0
these O 0
cases O 0
, O 0
histological O 0
investigations O 0
revealed O 0
marked O 0
changes O 0
in O 0
the O 0
heart O 0
that O 0
were O 0
consistent O 0
with O 0
DOX B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

Sequential O 0
measurements O 0
of O 0
cardiac O 0
output O 0
in O 0
surviving O 0
animals O 0
that O 0
received O 0
either O 0
free O 0
DOX B-Chemical 0
or O 0
the O 0
mixture O 0
of O 0
HPMA B-Chemical 0
copolymer O 0
and O 0
free O 0
DOX B-Chemical 0
showed O 0
a O 0
reduction O 0
of O 0
approximately O 0
30 O 0
% O 0
in O 0
function O 0
beginning O 0
at O 0
the O 0
4th O 0
week O 0
after O 0
drug O 0
administration O 0
. O 0

The O 0
heart O 0
rate O 0
in O 0
these O 0
animals O 0
was O 0
approximately O 0
12 O 0
% O 0
lower O 0
than O 0
that O 0
measured O 0
in O 0
age O 0
- O 0
matched O 0
control O 0
rats O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Animals O 0
that O 0
were O 0
given O 0
the O 0
HPMA B-Chemical 0
copolymer O 0
conjugates O 0
containing O 0
DOX B-Chemical 0
exhibited O 0
no O 0
significant O 0
change O 0
in O 0
cardiac O 0
output O 0
throughout O 0
the O 0
study O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

In O 0
addition O 0
, O 0
no O 0
significant O 0
histological O 0
change O 0
was O 0
observed O 0
in O 0
the O 0
heart O 0
of O 0
animals O 0
that O 0
received O 0
DOX B-Chemical 0
in O 0
the O 0
form O 0
of O 0
HPMA B-Chemical 0
copolymer O 0
conjugates O 0
and O 0
were O 0
killed O 0
at O 0
the O 0
end O 0
of O 0
the O 0
study O 0
. O 0

However O 0
, O 0
these O 0
animals O 0
had O 0
shown O 0
a O 0
significant O 0
increase O 0
in O 0
heart O 0
rate O 0
beginning O 0
at O 0
8 O 0
weeks O 0
after O 0
drug O 0
administration O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
400 O 0
WORDS O 0
) O 0

Corneal B-Disease 0
ulcers I-Disease 0
associated O 0
with O 0
aerosolized O 0
crack B-Chemical 0
cocaine I-Chemical 0
use O 0
. O 0

PURPOSE O 0
: O 0
We O 0
report O 0
4 O 0
cases O 0
of O 0
corneal B-Disease 0
ulcers I-Disease 0
associated O 0
with O 0
drug B-Disease 0
abuse I-Disease 0
. O 0

The O 0
pathogenesis O 0
of O 0
these O 0
ulcers B-Disease 0
and O 0
management O 0
of O 0
these O 0
patients O 0
are O 0
also O 0
reviewed O 0
. O 0

METHODS O 0
: O 0
Review O 0
of O 0
all O 0
cases O 0
of O 0
corneal B-Disease 0
ulcers I-Disease 0
associated O 0
with O 0
drug B-Disease 0
abuse I-Disease 0
seen O 0
at O 0
our O 0
institution O 0
from O 0
July O 0
2006 O 0
to O 0
December O 0
2006 O 0
. O 0

RESULTS O 0
: O 0
Four O 0
patients O 0
with O 0
corneal B-Disease 0
ulcers I-Disease 0
associated O 0
with O 0
crack B-Chemical 0
cocaine I-Chemical 0
use O 0
were O 0
reviewed O 0
. O 0

All O 0
corneal B-Disease 0
ulcers I-Disease 0
were O 0
cultured O 0
, O 0
and O 0
the O 0
patients O 0
were O 0
admitted O 0
to O 0
the O 0
hospital O 0
for O 0
intensive O 0
topical O 0
antibiotic O 0
treatment O 0
. O 0

Each O 0
patient O 0
received O 0
comprehensive O 0
health O 0
care O 0
, O 0
including O 0
medical O 0
and O 0
substance B-Disease 0
abuse I-Disease 0
consultations O 0
. O 0

Streptococcal O 0
organisms O 0
were O 0
found O 0
in O 0
3 O 0
cases O 0
and O 0
Capnocytophaga O 0
and O 0
Brevibacterium O 0
casei O 0
in O 0
1 O 0
patient O 0
. O 0

The O 0
infections B-Disease 0
responded O 0
to O 0
antibiotic O 0
treatment O 0
. O 0

Two O 0
patients O 0
needed O 0
a O 0
lateral O 0
tarsorrhaphy O 0
for O 0
persistent O 0
epithelial B-Disease 0
defects I-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
Aerosolized O 0
crack B-Chemical 0
cocaine I-Chemical 0
use O 0
can O 0
be O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
corneal B-Disease 0
ulcers I-Disease 0
. O 0

Drug B-Disease 0
abuse I-Disease 0
provides O 0
additional O 0
challenges O 0
for O 0
management O 0
. O 0

Not O 0
only O 0
treatment O 0
of O 0
their O 0
infections B-Disease 0
but O 0
also O 0
the O 0
overall O 0
poor O 0
health O 0
of O 0
the O 0
patients O 0
and O 0
increased O 0
risk O 0
of O 0
noncompliance O 0
need O 0
to O 0
be O 0
addressed O 0
. O 0

Comprehensive O 0
care O 0
may O 0
provide O 0
the O 0
patient O 0
the O 0
opportunity O 0
to O 0
discontinue O 0
their O 0
substance B-Disease 0
abuse I-Disease 0
, O 0
improve O 0
their O 0
overall O 0
health O 0
, O 0
and O 0
prevent O 0
future O 0
corneal O 0
complications O 0
. O 0

Topical O 0
0 O 0
. O 0
025 O 0
% O 0
capsaicin B-Chemical 0
in O 0
chronic O 0
post B-Disease 0
- I-Disease 0
herpetic I-Disease 0
neuralgia I-Disease 0
: O 0
efficacy O 0
, O 0
predictors O 0
of O 0
response O 0
and O 0
long O 0
- O 0
term O 0
course O 0
. O 0

In O 0
order O 0
to O 0
evaluate O 0
the O 0
efficacy O 0
, O 0
time O 0
- O 0
course O 0
of O 0
action O 0
and O 0
predictors O 0
of O 0
response O 0
to O 0
topical O 0
capsaicin B-Chemical 0
, O 0
39 O 0
patients O 0
with O 0
chronic O 0
post B-Disease 0
- I-Disease 0
herpetic I-Disease 0
neuralgia I-Disease 0
( O 0
PHN B-Disease 0
) O 0
, O 0
median O 0
duration O 0
24 O 0
months O 0
, O 0
were O 0
treated O 0
with O 0
0 O 0
. O 0
025 O 0
% O 0
capsaicin B-Chemical 0
cream O 0
for O 0
8 O 0
weeks O 0
. O 0

During O 0
therapy O 0
the O 0
patients O 0
rated O 0
their O 0
pain B-Disease 0
on O 0
a O 0
visual O 0
analogue O 0
scale O 0
( O 0
VAS O 0
) O 0
and O 0
a O 0
verbal O 0
outcome O 0
scale O 0
. O 0

A O 0
follow O 0
- O 0
up O 0
investigation O 0
was O 0
performed O 0
10 O 0
- O 0
12 O 0
months O 0
after O 0
study O 0
onset O 0
on O 0
the O 0
patients O 0
who O 0
had O 0
improved O 0
. O 0

Nineteen O 0
patients O 0
( O 0
48 O 0
. O 0
7 O 0
% O 0
) O 0
substantially O 0
improved O 0
after O 0
the O 0
8 O 0
- O 0
week O 0
trial O 0
; O 0
5 O 0
( O 0
12 O 0
. O 0
8 O 0
% O 0
) O 0
discontinued O 0
therapy O 0
due O 0
to O 0
side O 0
- O 0
effects O 0
such O 0
as O 0
intolerable O 0
capsaicin B-Chemical 0
- O 0
induced O 0
burning O 0
sensations O 0
( O 0
4 O 0
) O 0
or O 0
mastitis B-Disease 0
( O 0
1 O 0
) O 0
; O 0
15 O 0
( O 0
38 O 0
. O 0
5 O 0
% O 0
) O 0
reported O 0
no O 0
benefit O 0
. O 0

The O 0
decrease O 0
in O 0
VAS O 0
ratings O 0
was O 0
significant O 0
after O 0
2 O 0
weeks O 0
of O 0
continuous O 0
application O 0
. O 0

Of O 0
the O 0
responders O 0
72 O 0
. O 0
2 O 0
% O 0
were O 0
still O 0
improved O 0
at O 0
the O 0
follow O 0
- O 0
up O 0
; O 0
only O 0
one O 0
- O 0
third O 0
of O 0
them O 0
had O 0
continued O 0
application O 0
irregularly O 0
. O 0

Treatment O 0
effect O 0
was O 0
not O 0
dependent O 0
on O 0
patient O 0
' O 0
s O 0
age O 0
, O 0
duration O 0
or O 0
localization O 0
of O 0
PHN B-Disease 0
( O 0
trigeminal O 0
involvement O 0
was O 0
excluded O 0
) O 0
, O 0
sensory B-Disease 0
disturbance I-Disease 0
or O 0
pain B-Disease 0
character O 0
. O 0

Treatment O 0
response O 0
was O 0
not O 0
correlated O 0
with O 0
the O 0
incidence O 0
, O 0
time O 0
- O 0
course O 0
or O 0
severity O 0
of O 0
capsaicin B-Chemical 0
- O 0
induced O 0
burning O 0
. O 0

If O 0
confirmed O 0
in O 0
controlled O 0
trials O 0
, O 0
the O 0
long O 0
- O 0
term O 0
results O 0
of O 0
this O 0
open O 0
, O 0
non O 0
- O 0
randomized O 0
study O 0
might O 0
indicate O 0
that O 0
the O 0
analgesic O 0
effect O 0
of O 0
capsaicin B-Chemical 0
in O 0
PHN B-Disease 0
is O 0
mediated O 0
by O 0
both O 0
interference O 0
with O 0
neuropeptide O 0
metabolism O 0
and O 0
morphological O 0
changes O 0
( O 0
perhaps O 0
degeneration O 0
) O 0
of O 0
nociceptive O 0
afferents O 0
. O 0

Myo B-Chemical 0
- I-Chemical 0
inositol I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
phosphate I-Chemical 0
( O 0
MIP B-Chemical 0
) O 0
synthase O 0
inhibition O 0
: O 0
in O 0
- O 0
vivo O 0
study O 0
in O 0
rats O 0
. O 0

Lithium B-Chemical 0
and O 0
valproate B-Chemical 0
are O 0
the O 0
prototypic O 0
mood O 0
stabilizers O 0
and O 0
have O 0
diverse O 0
structures O 0
and O 0
targets O 0
. O 0

Both O 0
drugs O 0
influence O 0
inositol B-Chemical 0
metabolism O 0
. O 0

Lithium B-Chemical 0
inhibits O 0
IMPase O 0
and O 0
valproate B-Chemical 0
inhibits O 0
MIP B-Chemical 0
synthase O 0
. O 0

This O 0
study O 0
shows O 0
that O 0
MIP B-Chemical 0
synthase O 0
inhibition O 0
does O 0
not O 0
replicate O 0
or O 0
augment O 0
the O 0
effects O 0
of O 0
lithium B-Chemical 0
in O 0
the O 0
inositol B-Chemical 0
sensitive O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
model O 0
. O 0

This O 0
lack O 0
of O 0
effects O 0
may O 0
stem O 0
from O 0
the O 0
low O 0
contribution O 0
of O 0
de O 0
- O 0
novo O 0
synthesis O 0
to O 0
cellular O 0
inositol B-Chemical 0
supply O 0
or O 0
to O 0
the O 0
inhibition O 0
of O 0
the O 0
de O 0
- O 0
novo O 0
synthesis O 0
by O 0
lithium B-Chemical 0
itself O 0
. O 0

Non O 0
- O 0
steroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
- O 0
associated O 0
acute O 0
interstitial B-Disease 0
nephritis I-Disease 0
with O 0
granular O 0
tubular O 0
basement O 0
membrane O 0
deposits O 0
. O 0

Acute B-Disease 0
tubulo I-Disease 0
- I-Disease 0
interstitial I-Disease 0
nephritis I-Disease 0
( O 0
ATIN B-Disease 0
) O 0
is O 0
an O 0
important O 0
cause O 0
of O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
resulting O 0
from O 0
a O 0
variety O 0
of O 0
insults O 0
, O 0
including O 0
immune O 0
complex O 0
- O 0
mediated O 0
tubulo B-Disease 0
- I-Disease 0
interstitial I-Disease 0
injury I-Disease 0
, O 0
but O 0
drugs O 0
such O 0
as O 0
non O 0
- O 0
steroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
( O 0
NSAIDs O 0
) O 0
are O 0
a O 0
far O 0
more O 0
frequent O 0
cause O 0
. O 0

Overall O 0
, O 0
as O 0
an O 0
entity O 0
, O 0
ATIN B-Disease 0
remains O 0
under O 0
- O 0
diagnosed O 0
, O 0
as O 0
symptoms O 0
resolve O 0
spontaneously O 0
if O 0
the O 0
medication O 0
is O 0
stopped O 0
. O 0

We O 0
report O 0
on O 0
a O 0
14 O 0
- O 0
year O 0
- O 0
old O 0
boy O 0
who O 0
developed O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
2 O 0
weeks O 0
after O 0
aortic O 0
valve O 0
surgery O 0
. O 0

He O 0
was O 0
put O 0
on O 0
aspirin B-Chemical 0
following O 0
surgery O 0
and O 0
took O 0
ibuprofen B-Chemical 0
for O 0
fever B-Disease 0
for O 0
nearly O 0
a O 0
week O 0
prior O 0
to O 0
presentation O 0
. O 0

He O 0
then O 0
presented O 0
to O 0
the O 0
emergency O 0
department O 0
feeling O 0
quite O 0
ill O 0
and O 0
was O 0
found O 0
to O 0
have O 0
a O 0
blood B-Chemical 0
urea I-Chemical 0
nitrogen I-Chemical 0
( O 0
BUN B-Chemical 0
) O 0
concentration O 0
of O 0
of O 0
147 O 0
mg O 0
/ O 0
dl O 0
, O 0
creatinine B-Chemical 0
of O 0
15 O 0
. O 0
3 O 0
mg O 0
/ O 0
dl O 0
and O 0
serum O 0
potassium B-Chemical 0
of O 0
8 O 0
. O 0
7 O 0
mEq O 0
/ O 0
l O 0
. O 0

Dialysis O 0
was O 0
immediately O 0
initiated O 0
. O 0

A O 0
kidney O 0
biopsy O 0
showed O 0
inflammatory O 0
infiltrate O 0
consistent O 0
with O 0
ATIN B-Disease 0
. O 0

However O 0
, O 0
in O 0
the O 0
tubular O 0
basement O 0
membrane O 0
( O 0
TBM O 0
) O 0
, O 0
very O 0
intense O 0
granular O 0
deposits O 0
of O 0
polyclonal O 0
IgG O 0
and O 0
C3 O 0
were O 0
noted O 0
. O 0

He O 0
needed O 0
dialysis O 0
for O 0
2 O 0
weeks O 0
and O 0
was O 0
treated O 0
successfully O 0
with O 0
steroids B-Chemical 0
for O 0
6 O 0
months O 0
. O 0

His O 0
renal O 0
recovery O 0
and O 0
disappearance O 0
of O 0
proteinuria B-Disease 0
took O 0
a O 0
year O 0
. O 0

In O 0
conclusion O 0
, O 0
this O 0
is O 0
a O 0
first O 0
report O 0
of O 0
NSAIDs O 0
- O 0
associated O 0
ATIN B-Disease 0
, O 0
showing O 0
deposits O 0
of O 0
granular O 0
immune O 0
complex O 0
present O 0
only O 0
in O 0
the O 0
TBM O 0
and O 0
not O 0
in O 0
the O 0
glomeruli O 0
. O 0

Rifampicin B-Chemical 0
- O 0
associated O 0
segmental O 0
necrotizing O 0
glomerulonephritis B-Disease 0
in O 0
staphylococcal B-Disease 0
endocarditis I-Disease 0
. O 0

Segmental O 0
necrotising O 0
glomerulonephritis B-Disease 0
has O 0
been O 0
reported O 0
as O 0
complication O 0
of O 0
rifampicin B-Chemical 0
therapy O 0
in O 0
patients O 0
receiving O 0
treatment O 0
for O 0
tuberculosis B-Disease 0
. O 0

Changing O 0
epidemiology O 0
of O 0
infections B-Disease 0
such O 0
as O 0
infective B-Disease 0
endocarditis I-Disease 0
( O 0
IE B-Disease 0
) O 0
has O 0
led O 0
to O 0
an O 0
increase O 0
in O 0
the O 0
use O 0
of O 0
rifampicin B-Chemical 0
for O 0
Staphylococcal B-Disease 0
infections I-Disease 0
. O 0

We O 0
describe O 0
a O 0
case O 0
of O 0
a O 0
patient O 0
with O 0
Staphylococcal B-Disease 0
IE I-Disease 0
who O 0
developed O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
secondary O 0
to O 0
a O 0
segmental O 0
necrotising O 0
glomerulonephritis B-Disease 0
while O 0
being O 0
treated O 0
with O 0
rifampicin B-Chemical 0
, O 0
and O 0
review O 0
the O 0
literature O 0
regarding O 0
this O 0
complication O 0
of O 0
rifampicin B-Chemical 0
therapy O 0
. O 0

Rate O 0
of O 0
YMDD O 0
motif O 0
mutants O 0
in O 0
lamivudine B-Chemical 0
- O 0
untreated O 0
Iranian O 0
patients O 0
with O 0
chronic B-Disease 0
hepatitis I-Disease 0
B I-Disease 0
virus I-Disease 0
infection I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Lamivudine B-Chemical 0
is O 0
used O 0
for O 0
the O 0
treatment O 0
of O 0
chronic B-Disease 0
hepatitis I-Disease 0
B I-Disease 0
patients O 0
. O 0

Recent O 0
studies O 0
show O 0
that O 0
the O 0
YMDD O 0
motif O 0
mutants O 0
( O 0
resistant O 0
hepatitis B-Disease 0
B I-Disease 0
virus O 0
) O 0
occur O 0
as O 0
natural O 0
genome O 0
variability O 0
in O 0
lamivudine B-Chemical 0
- O 0
untreated O 0
chronic B-Disease 0
hepatitis I-Disease 0
B I-Disease 0
patients O 0
. O 0

In O 0
this O 0
study O 0
we O 0
aimed O 0
to O 0
determine O 0
the O 0
rate O 0
of O 0
YMDD O 0
motif O 0
mutants O 0
in O 0
lamivudine B-Chemical 0
- O 0
untreated O 0
chronic B-Disease 0
hepatitis I-Disease 0
B I-Disease 0
patients O 0
in O 0
Iran O 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
A O 0
total O 0
of O 0
77 O 0
chronic B-Disease 0
hepatitis I-Disease 0
B I-Disease 0
patients O 0
who O 0
had O 0
not O 0
been O 0
treated O 0
with O 0
lamivudine B-Chemical 0
were O 0
included O 0
in O 0
the O 0
study O 0
. O 0

Serum O 0
samples O 0
from O 0
patients O 0
were O 0
tested O 0
by O 0
polymerase O 0
chain O 0
reaction O 0
- O 0
restriction O 0
fragment O 0
length O 0
polymorphism O 0
( O 0
PCR O 0
- O 0
RFLP O 0
) O 0
for O 0
detection O 0
of O 0
YMDD O 0
motif O 0
mutants O 0
. O 0

All O 0
patients O 0
were O 0
also O 0
tested O 0
for O 0
liver O 0
enzymes O 0
, O 0
anti O 0
- O 0
HCV O 0
, O 0
HBeAg B-Chemical 0
, O 0
and O 0
anti O 0
- O 0
HBe O 0
. O 0

RESULTS O 0
: O 0
Of O 0
the O 0
77 O 0
patients O 0
enrolled O 0
in O 0
the O 0
study O 0
, O 0
73 O 0
% O 0
were O 0
male O 0
and O 0
27 O 0
% O 0
were O 0
female O 0
. O 0

Mean O 0
ALT O 0
and O 0
AST O 0
levels O 0
were O 0
124 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
73 O 0
. O 0
4 O 0
and O 0
103 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
81 O 0
IU O 0
/ O 0
l O 0
, O 0
respectively O 0
. O 0

HBeAg B-Chemical 0
was O 0
positive O 0
in O 0
40 O 0
% O 0
and O 0
anti O 0
- O 0
HBe O 0
in O 0
60 O 0
% O 0
of O 0
the O 0
patients O 0
. O 0

Anti O 0
- O 0
HCV O 0
was O 0
negative O 0
in O 0
all O 0
of O 0
them O 0
. O 0

YMDD O 0
motif O 0
mutants O 0
were O 0
not O 0
detected O 0
in O 0
any O 0
of O 0
the O 0
patients O 0
despite O 0
the O 0
liver O 0
enzyme O 0
levels O 0
and O 0
the O 0
presence O 0
of O 0
HBeAg B-Chemical 0
or O 0
anti O 0
- O 0
HBe O 0
. O 0

CONCLUSION O 0
: O 0
Although O 0
the O 0
natural O 0
occurrence O 0
of O 0
YMDD O 0
motif O 0
mutants O 0
in O 0
lamivudine B-Chemical 0
- O 0
untreated O 0
patients O 0
with O 0
chronic B-Disease 0
hepatitis I-Disease 0
B I-Disease 0
has O 0
been O 0
reported O 0
, O 0
these O 0
mutants O 0
were O 0
not O 0
detected O 0
in O 0
Iranian O 0
lamivudine B-Chemical 0
- O 0
untreated O 0
chronic B-Disease 0
hepatitis I-Disease 0
B I-Disease 0
patients O 0
. O 0

Branch O 0
retinal B-Disease 0
vein I-Disease 0
occlusion I-Disease 0
and O 0
fluoxetine B-Chemical 0
. O 0

A O 0
case O 0
of O 0
branch O 0
retinal B-Disease 0
vein I-Disease 0
occlusion I-Disease 0
associated O 0
with O 0
fluoxetine B-Chemical 0
- O 0
induced O 0
secondary O 0
hypertension B-Disease 0
is O 0
described O 0
. O 0

Although O 0
an O 0
infrequent O 0
complication O 0
of O 0
selective O 0
serotonin B-Chemical 0
reuptake O 0
inhibitor O 0
therapy O 0
, O 0
it O 0
is O 0
important O 0
that O 0
ophthalmologists O 0
are O 0
aware O 0
that O 0
these O 0
agents O 0
can O 0
cause O 0
hypertension B-Disease 0
because O 0
this O 0
class O 0
of O 0
drugs O 0
is O 0
widely O 0
prescribed O 0
. O 0

The O 0
differential O 0
effects O 0
of O 0
bupivacaine B-Chemical 0
and O 0
lidocaine B-Chemical 0
on O 0
prostaglandin B-Chemical 0
E2 I-Chemical 0
release O 0
, O 0
cyclooxygenase O 0
gene O 0
expression O 0
and O 0
pain B-Disease 0
in O 0
a O 0
clinical O 0
pain B-Disease 0
model O 0
. O 0

BACKGROUND O 0
: O 0
In O 0
addition O 0
to O 0
blocking O 0
nociceptive O 0
input O 0
from O 0
surgical O 0
sites O 0
, O 0
long O 0
- O 0
acting O 0
local O 0
anesthetics O 0
might O 0
directly O 0
modulate O 0
inflammation B-Disease 0
. O 0

In O 0
the O 0
present O 0
study O 0
, O 0
we O 0
describe O 0
the O 0
proinflammatory O 0
effects O 0
of O 0
bupivacaine B-Chemical 0
on O 0
local O 0
prostaglandin B-Chemical 0
E2 I-Chemical 0
( O 0
PGE2 B-Chemical 0
) O 0
production O 0
and O 0
cyclooxygenase O 0
( O 0
COX O 0
) O 0
gene O 0
expression O 0
that O 0
increases O 0
postoperative B-Disease 0
pain I-Disease 0
in O 0
human O 0
subjects O 0
. O 0

METHODS O 0
: O 0
Subjects O 0
( O 0
n O 0
= O 0
114 O 0
) O 0
undergoing O 0
extraction O 0
of O 0
impacted O 0
third O 0
molars O 0
received O 0
either O 0
2 O 0
% O 0
lidocaine B-Chemical 0
or O 0
0 O 0
. O 0
5 O 0
% O 0
bupivacaine B-Chemical 0
before O 0
surgery O 0
and O 0
either O 0
rofecoxib B-Chemical 0
50 O 0
mg O 0
or O 0
placebo O 0
orally O 0
90 O 0
min O 0
before O 0
surgery O 0
and O 0
for O 0
the O 0
following O 0
48 O 0
h O 0
. O 0

Oral O 0
mucosal O 0
biopsies O 0
were O 0
taken O 0
before O 0
surgery O 0
and O 0
48 O 0
h O 0
after O 0
surgery O 0
. O 0

After O 0
extraction O 0
, O 0
a O 0
microdialysis O 0
probe O 0
was O 0
placed O 0
at O 0
the O 0
surgical O 0
site O 0
for O 0
PGE2 B-Chemical 0
and O 0
thromboxane B-Chemical 0
B2 I-Chemical 0
( O 0
TXB2 B-Chemical 0
) O 0
measurements O 0
. O 0

RESULTS O 0
: O 0
The O 0
bupivacaine B-Chemical 0
/ O 0
rofecoxib B-Chemical 0
group O 0
reported O 0
significantly O 0
less O 0
pain B-Disease 0
, O 0
as O 0
assessed O 0
by O 0
a O 0
visual O 0
analog O 0
scale O 0
, O 0
compared O 0
with O 0
the O 0
other O 0
three O 0
treatment O 0
groups O 0
over O 0
the O 0
first O 0
4 O 0
h O 0
. O 0

However O 0
, O 0
the O 0
bupivacaine B-Chemical 0
/ O 0
placebo O 0
group O 0
reported O 0
significantly O 0
more O 0
pain B-Disease 0
at O 0
24 O 0
h O 0
and O 0
PGE2 B-Chemical 0
levels O 0
during O 0
the O 0
first O 0
4 O 0
h O 0
were O 0
significantly O 0
higher O 0
than O 0
the O 0
other O 0
three O 0
treatment O 0
groups O 0
. O 0

Moreover O 0
, O 0
bupivacaine B-Chemical 0
significantly O 0
increased O 0
COX O 0
- O 0
2 O 0
gene O 0
expression O 0
at O 0
48 O 0
h O 0
as O 0
compared O 0
with O 0
the O 0
lidocaine B-Chemical 0
/ O 0
placebo O 0
group O 0
. O 0

Thromboxane B-Chemical 0
levels O 0
were O 0
not O 0
significantly O 0
affected O 0
by O 0
any O 0
of O 0
the O 0
treatments O 0
, O 0
indicating O 0
that O 0
the O 0
effects O 0
seen O 0
were O 0
attributable O 0
to O 0
inhibition O 0
of O 0
COX O 0
- O 0
2 O 0
, O 0
but O 0
not O 0
COX O 0
- O 0
1 O 0
. O 0

CONCLUSIONS O 0
: O 0
These O 0
results O 0
suggest O 0
that O 0
bupivacaine B-Chemical 0
stimulates O 0
COX O 0
- O 0
2 O 0
gene O 0
expression O 0
after O 0
tissue B-Disease 0
injury I-Disease 0
, O 0
which O 0
is O 0
associated O 0
with O 0
higher O 0
PGE2 B-Chemical 0
production O 0
and O 0
pain B-Disease 0
after O 0
the O 0
local O 0
anesthetic O 0
effect O 0
dissipates O 0
. O 0

p75NTR O 0
expression O 0
in O 0
rat O 0
urinary O 0
bladder O 0
sensory O 0
neurons O 0
and O 0
spinal O 0
cord O 0
with O 0
cyclophosphamide B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
. O 0

A O 0
role O 0
for O 0
nerve O 0
growth O 0
factor O 0
( O 0
NGF O 0
) O 0
in O 0
contributing O 0
to O 0
increased O 0
voiding O 0
frequency O 0
and O 0
altered O 0
sensation O 0
from O 0
the O 0
urinary O 0
bladder O 0
has O 0
been O 0
suggested O 0
. O 0

Previous O 0
studies O 0
have O 0
examined O 0
the O 0
expression O 0
and O 0
regulation O 0
of O 0
tyrosine B-Chemical 0
kinase O 0
receptors O 0
( O 0
Trks O 0
) O 0
in O 0
micturition O 0
reflexes O 0
with O 0
urinary B-Disease 0
bladder I-Disease 0
inflammation I-Disease 0
. O 0

The O 0
present O 0
studies O 0
examine O 0
the O 0
expression O 0
and O 0
regulation O 0
of O 0
another O 0
receptor O 0
known O 0
to O 0
bind O 0
NGF O 0
, O 0
p75 O 0
( O 0
NTR O 0
) O 0
, O 0
after O 0
various O 0
durations O 0
of O 0
bladder B-Disease 0
inflammation I-Disease 0
induced O 0
by O 0
cyclophosphamide B-Chemical 0
( O 0
CYP B-Chemical 0
) O 0
. O 0

CYP B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
increased O 0
( O 0
P O 0
< O 0
or O 0
= O 0
0 O 0
. O 0
001 O 0
) O 0
p75 O 0
( O 0
NTR O 0
) O 0
expression O 0
in O 0
the O 0
superficial O 0
lateral O 0
and O 0
medial O 0
dorsal O 0
horn O 0
in O 0
L1 O 0
- O 0
L2 O 0
and O 0
L6 O 0
- O 0
S1 O 0
spinal O 0
segments O 0
. O 0

The O 0
number O 0
of O 0
p75 O 0
( O 0
NTR O 0
) O 0
- O 0
immunoreactive O 0
( O 0
- O 0
IR O 0
) O 0
cells O 0
in O 0
the O 0
lumbosacral O 0
dorsal O 0
root O 0
ganglia O 0
( O 0
DRG O 0
) O 0
also O 0
increased O 0
( O 0
P O 0
< O 0
or O 0
= O 0
0 O 0
. O 0
05 O 0
) O 0
with O 0
CYP B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
( O 0
acute O 0
, O 0
intermediate O 0
, O 0
and O 0
chronic O 0
) O 0
. O 0

Quantitative O 0
, O 0
real O 0
- O 0
time O 0
polymerase O 0
chain O 0
reaction O 0
also O 0
demonstrated O 0
significant O 0
increases O 0
( O 0
P O 0
< O 0
or O 0
= O 0
0 O 0
. O 0
01 O 0
) O 0
in O 0
p75 O 0
( O 0
NTR O 0
) O 0
mRNA O 0
in O 0
DRG O 0
with O 0
intermediate O 0
and O 0
chronic O 0
CYP B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
. O 0

Retrograde O 0
dye O 0
- O 0
tracing O 0
techniques O 0
with O 0
Fastblue O 0
were O 0
used O 0
to O 0
identify O 0
presumptive O 0
bladder O 0
afferent O 0
cells O 0
in O 0
the O 0
lumbosacral O 0
DRG O 0
. O 0

In O 0
bladder O 0
afferent O 0
cells O 0
in O 0
DRG O 0
, O 0
p75 O 0
( O 0
NTR O 0
) O 0
- O 0
IR O 0
was O 0
also O 0
increased O 0
( O 0
P O 0
< O 0
or O 0
= O 0
0 O 0
. O 0
01 O 0
) O 0
with O 0
cystitis B-Disease 0
. O 0

In O 0
addition O 0
to O 0
increases O 0
in O 0
p75 O 0
( O 0
NTR O 0
) O 0
- O 0
IR O 0
in O 0
DRG O 0
cell O 0
bodies O 0
, O 0
increases O 0
( O 0
P O 0
< O 0
or O 0
= O 0
0 O 0
. O 0
001 O 0
) O 0
in O 0
pericellular O 0
( O 0
encircling O 0
DRG O 0
cells O 0
) O 0
p75 O 0
( O 0
NTR O 0
) O 0
- O 0
IR O 0
in O 0
DRG O 0
also O 0
increased O 0
. O 0

Confocal O 0
analyses O 0
demonstrated O 0
that O 0
pericellular O 0
p75 O 0
( O 0
NTR O 0
) O 0
- O 0
IR O 0
was O 0
not O 0
colocalized O 0
with O 0
the O 0
glial O 0
marker O 0
, O 0
glial O 0
fibrillary O 0
acidic O 0
protein O 0
( O 0
GFAP O 0
) O 0
. O 0

These O 0
studies O 0
demonstrate O 0
that O 0
p75 O 0
( O 0
NTR O 0
) O 0
expression O 0
in O 0
micturition O 0
reflexes O 0
is O 0
present O 0
constitutively O 0
and O 0
modified O 0
by O 0
bladder B-Disease 0
inflammation I-Disease 0
. O 0

The O 0
functional O 0
significance O 0
of O 0
p75 O 0
( O 0
NTR O 0
) O 0
expression O 0
in O 0
micturition O 0
reflexes O 0
remains O 0
to O 0
be O 0
determined O 0
. O 0

Azathioprine B-Chemical 0
- O 0
induced O 0
suicidal O 0
erythrocyte O 0
death O 0
. O 0

BACKGROUND O 0
: O 0
Azathioprine B-Chemical 0
is O 0
widely O 0
used O 0
as O 0
an O 0
immunosuppressive O 0
drug O 0
. O 0

The O 0
side O 0
effects O 0
of O 0
azathioprine B-Chemical 0
include O 0
anemia B-Disease 0
, O 0
which O 0
has O 0
been O 0
attributed O 0
to O 0
bone O 0
marrow O 0
suppression O 0
. O 0

Alternatively O 0
, O 0
anemia B-Disease 0
could O 0
result O 0
from O 0
accelerated O 0
suicidal O 0
erythrocyte O 0
death O 0
or O 0
eryptosis O 0
, O 0
which O 0
is O 0
characterized O 0
by O 0
exposure O 0
of O 0
phosphatidylserine B-Chemical 0
( O 0
PS B-Chemical 0
) O 0
at O 0
the O 0
erythrocyte O 0
surface O 0
and O 0
by O 0
cell O 0
shrinkage O 0
. O 0

METHODS O 0
: O 0
The O 0
present O 0
experiments O 0
explored O 0
whether O 0
azathioprine B-Chemical 0
influences O 0
eryptosis O 0
. O 0

According O 0
to O 0
annexin O 0
V O 0
binding O 0
, O 0
erythrocytes O 0
from O 0
patients O 0
indeed O 0
showed O 0
a O 0
significant O 0
increase O 0
of O 0
PS B-Chemical 0
exposure O 0
within O 0
1 O 0
week O 0
of O 0
treatment O 0
with O 0
azathioprine B-Chemical 0
. O 0

In O 0
a O 0
second O 0
series O 0
, O 0
cytosolic O 0
Ca2 B-Chemical 0
+ O 0
activity O 0
( O 0
Fluo3 B-Chemical 0
fluorescence O 0
) O 0
, O 0
cell O 0
volume O 0
( O 0
forward O 0
scatter O 0
) O 0
, O 0
and O 0
PS B-Chemical 0
- O 0
exposure O 0
( O 0
annexin O 0
V O 0
binding O 0
) O 0
were O 0
determined O 0
by O 0
FACS O 0
analysis O 0
in O 0
erythrocytes O 0
from O 0
healthy O 0
volunteers O 0
. O 0

RESULTS O 0
: O 0
Exposure O 0
to O 0
azathioprine B-Chemical 0
( O 0
> O 0
or O 0
= O 0
2 O 0
microg O 0
/ O 0
mL O 0
) O 0
for O 0
48 O 0
hours O 0
increased O 0
cytosolic O 0
Ca2 B-Chemical 0
+ O 0
activity O 0
and O 0
annexin O 0
V O 0
binding O 0
and O 0
decreased O 0
forward O 0
scatter O 0
. O 0

The O 0
effect O 0
of O 0
azathioprine B-Chemical 0
on O 0
both O 0
annexin O 0
V O 0
binding O 0
and O 0
forward O 0
scatter O 0
was O 0
significantly O 0
blunted O 0
in O 0
the O 0
nominal O 0
absence O 0
of O 0
extracellular O 0
Ca2 B-Chemical 0
+ O 0
. O 0

CONCLUSIONS O 0
: O 0
Azathioprine B-Chemical 0
triggers O 0
suicidal O 0
erythrocyte O 0
death O 0
, O 0
an O 0
effect O 0
presumably O 0
contributing O 0
to O 0
azathioprine B-Chemical 0
- O 0
induced O 0
anemia B-Disease 0
. O 0

Levetiracetam B-Chemical 0
as O 0
an O 0
adjunct O 0
to O 0
phenobarbital B-Chemical 0
treatment O 0
in O 0
cats O 0
with O 0
suspected O 0
idiopathic B-Disease 0
epilepsy I-Disease 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
assess O 0
pharmacokinetics O 0
, O 0
efficacy O 0
, O 0
and O 0
tolerability O 0
of O 0
oral O 0
levetiracetam B-Chemical 0
administered O 0
as O 0
an O 0
adjunct O 0
to O 0
phenobarbital B-Chemical 0
treatment O 0
in O 0
cats O 0
with O 0
poorly O 0
controlled O 0
suspected O 0
idiopathic B-Disease 0
epilepsy I-Disease 0
. O 0

DESIGN O 0
- O 0
Open O 0
- O 0
label O 0
, O 0
noncomparative O 0
clinical O 0
trial O 0
. O 0

ANIMALS O 0
: O 0
12 O 0
cats O 0
suspected O 0
to O 0
have O 0
idiopathic B-Disease 0
epilepsy I-Disease 0
that O 0
was O 0
poorly O 0
controlled O 0
with O 0
phenobarbital B-Chemical 0
or O 0
that O 0
had O 0
unacceptable O 0
adverse O 0
effects O 0
when O 0
treated O 0
with O 0
phenobarbital B-Chemical 0
. O 0

PROCEDURES O 0
: O 0
Cats O 0
were O 0
treated O 0
with O 0
levetiracetam B-Chemical 0
( O 0
20 O 0
mg O 0
/ O 0
kg O 0
[ O 0
9 O 0
. O 0
1 O 0
mg O 0
/ O 0
lb O 0
] O 0
, O 0
PO O 0
, O 0
q O 0
8 O 0
h O 0
) O 0
. O 0

After O 0
a O 0
minimum O 0
of O 0
1 O 0
week O 0
of O 0
treatment O 0
, O 0
serum O 0
levetiracetam B-Chemical 0
concentrations O 0
were O 0
measured O 0
before O 0
and O 0
2 O 0
, O 0
4 O 0
, O 0
and O 0
6 O 0
hours O 0
after O 0
drug O 0
administration O 0
, O 0
and O 0
maximum O 0
and O 0
minimum O 0
serum O 0
concentrations O 0
and O 0
elimination O 0
half O 0
- O 0
life O 0
were O 0
calculated O 0
. O 0

Seizure B-Disease 0
frequencies O 0
before O 0
and O 0
after O 0
initiation O 0
of O 0
levetiracetam B-Chemical 0
treatment O 0
were O 0
compared O 0
, O 0
and O 0
adverse O 0
effects O 0
were O 0
recorded O 0
. O 0

RESULTS O 0
: O 0
Median O 0
maximum O 0
serum O 0
levetiracetam B-Chemical 0
concentration O 0
was O 0
25 O 0
. O 0
5 O 0
microg O 0
/ O 0
mL O 0
, O 0
median O 0
minimum O 0
serum O 0
levetiracetam B-Chemical 0
concentration O 0
was O 0
8 O 0
. O 0
3 O 0
microg O 0
/ O 0
mL O 0
, O 0
and O 0
median O 0
elimination O 0
half O 0
- O 0
life O 0
was O 0
2 O 0
. O 0
9 O 0
hours O 0
. O 0

Median O 0
seizure B-Disease 0
frequency O 0
prior O 0
to O 0
treatment O 0
with O 0
levetiracetam B-Chemical 0
( O 0
2 O 0
. O 0
1 O 0
seizures B-Disease 0
/ O 0
mo O 0
) O 0
was O 0
significantly O 0
higher O 0
than O 0
median O 0
seizure B-Disease 0
frequency O 0
after O 0
initiation O 0
of O 0
levetiracetam B-Chemical 0
treatment O 0
( O 0
0 O 0
. O 0
42 O 0
seizures B-Disease 0
/ O 0
mo O 0
) O 0
, O 0
and O 0
7 O 0
of O 0
10 O 0
cats O 0
were O 0
classified O 0
as O 0
having O 0
responded O 0
to O 0
levetiracetam B-Chemical 0
treatment O 0
( O 0
ie O 0
, O 0
reduction O 0
in O 0
seizure B-Disease 0
frequency O 0
of O 0
> O 0
or O 0
= O 0
50 O 0
% O 0
) O 0
. O 0

Two O 0
cats O 0
had O 0
transient O 0
lethargy B-Disease 0
and O 0
inappetence B-Disease 0
. O 0

CONCLUSIONS O 0
AND O 0
CLINICAL O 0
RELEVANCE O 0
: O 0
Results O 0
suggested O 0
that O 0
levetiracetam B-Chemical 0
is O 0
well O 0
tolerated O 0
in O 0
cats O 0
and O 0
may O 0
be O 0
useful O 0
as O 0
an O 0
adjunct O 0
to O 0
phenobarbital B-Chemical 0
treatment O 0
in O 0
cats O 0
with O 0
idiopathic B-Disease 0
epilepsy I-Disease 0
. O 0

Serotonin B-Chemical 0
reuptake O 0
inhibitors O 0
, O 0
paranoia B-Disease 0
, O 0
and O 0
the O 0
ventral O 0
basal O 0
ganglia O 0
. O 0

Antidepressants O 0
have O 0
previously O 0
been O 0
associated O 0
with O 0
paranoid B-Disease 0
reactions O 0
in O 0
psychiatric O 0
patients O 0
. O 0

Five O 0
cases O 0
of O 0
paranoid B-Disease 0
exacerbation O 0
with O 0
the O 0
serotonin B-Chemical 0
reuptake O 0
inhibitors O 0
fluoxetine B-Chemical 0
and O 0
amitriptyline B-Chemical 0
are O 0
reported O 0
here O 0
. O 0

Elements O 0
common O 0
to O 0
these O 0
cases O 0
included O 0
a O 0
history O 0
of O 0
paranoid B-Disease 0
symptomatology O 0
and O 0
the O 0
concomitant O 0
occurrence O 0
of O 0
depressive B-Disease 0
and I-Disease 0
psychotic I-Disease 0
symptoms I-Disease 0
. O 0

Complicated O 0
depressive B-Disease 0
disorders I-Disease 0
( O 0
including O 0
atypicality O 0
of O 0
course O 0
and O 0
symptomatology O 0
, O 0
chronicity O 0
, O 0
psychosis B-Disease 0
, O 0
bipolarity O 0
, O 0
and O 0
secondary O 0
onset O 0
in O 0
the O 0
course O 0
of O 0
a O 0
primary O 0
psychosis B-Disease 0
) O 0
may O 0
present O 0
particular O 0
vulnerability O 0
to O 0
paranoid B-Disease 0
exacerbations O 0
associated O 0
with O 0
serotonin B-Chemical 0
reuptake O 0
inhibitors O 0
. O 0

Although O 0
the O 0
pharmacology O 0
and O 0
neurobiology O 0
of O 0
paranoia B-Disease 0
remain O 0
cryptic O 0
, O 0
several O 0
mechanisms O 0
, O 0
including O 0
5HT3 O 0
receptor O 0
- O 0
mediated O 0
dopamine B-Chemical 0
release O 0
, O 0
beta O 0
- O 0
noradrenergic O 0
receptor O 0
downregulation O 0
, O 0
or O 0
GABAB O 0
receptor O 0
upregulation O 0
acting O 0
in O 0
the O 0
vicinity O 0
of O 0
the O 0
ventral O 0
basal O 0
ganglia O 0
( O 0
possibly O 0
in O 0
lateral O 0
orbitofrontal O 0
or O 0
anterior O 0
cingulate O 0
circuits O 0
) O 0
, O 0
might O 0
apply O 0
to O 0
this O 0
phenomenon O 0
. O 0

These O 0
cases O 0
call O 0
attention O 0
to O 0
possible O 0
paranoid B-Disease 0
exacerbations O 0
with O 0
serotonin B-Chemical 0
reuptake O 0
blockers O 0
in O 0
select O 0
patients O 0
and O 0
raise O 0
neurobiological O 0
considerations O 0
regarding O 0
paranoia B-Disease 0
. O 0

Clinical O 0
comparison O 0
of O 0
cardiorespiratory O 0
effects O 0
during O 0
unilateral O 0
and O 0
conventional O 0
spinal O 0
anaesthesia O 0
. O 0

BACKGROUND O 0
: O 0
Spinal O 0
anaesthesia O 0
is O 0
widely O 0
employed O 0
in O 0
clinical O 0
practice O 0
but O 0
has O 0
the O 0
main O 0
drawback O 0
of O 0
post O 0
- O 0
spinal O 0
block O 0
hypotension B-Disease 0
. O 0

Efforts O 0
must O 0
therefore O 0
continue O 0
to O 0
be O 0
made O 0
to O 0
obviate O 0
this O 0
setback O 0
OBJECTIVE O 0
: O 0
To O 0
evaluate O 0
the O 0
cardiovascular O 0
and O 0
respiratory O 0
changes O 0
during O 0
unilateral O 0
and O 0
conventional O 0
spinal O 0
anaesthesia O 0
. O 0

METHODS O 0
: O 0
With O 0
ethical O 0
approval O 0
, O 0
we O 0
studied O 0
74 O 0
American O 0
Society O 0
of O 0
Anesthesiologists O 0
( O 0
ASA O 0
) O 0
, O 0
physical O 0
status O 0
class O 0
1 O 0
and O 0
2 O 0
patients O 0
scheduled O 0
for O 0
elective O 0
unilateral O 0
lower O 0
limb O 0
surgery O 0
. O 0

Patients O 0
were O 0
randomly O 0
allocated O 0
into O 0
one O 0
of O 0
two O 0
groups O 0
: O 0
lateral O 0
and O 0
conventional O 0
spinal O 0
anaesthesia O 0
groups O 0
. O 0

In O 0
the O 0
lateral O 0
position O 0
with O 0
operative O 0
side O 0
down O 0
, O 0
patients O 0
recived O 0
10 O 0
mg O 0
( O 0
2mls O 0
) O 0
of O 0
0 O 0
. O 0
5 O 0
% O 0
hyperbaric O 0
bupivacaine B-Chemical 0
through O 0
a O 0
25 O 0
- O 0
gauge O 0
spinal O 0
needle O 0
. O 0

Patients O 0
in O 0
the O 0
unilateral O 0
group O 0
were O 0
maintained O 0
in O 0
the O 0
lateral O 0
position O 0
for O 0
15 O 0
minutes O 0
following O 0
spinal O 0
injection O 0
while O 0
those O 0
in O 0
the O 0
conventional O 0
group O 0
were O 0
turned O 0
supine O 0
immediately O 0
after O 0
injection O 0
. O 0

Blood O 0
pressure O 0
, O 0
heart O 0
rate O 0
, O 0
respiratory O 0
rate O 0
and O 0
oxygen B-Chemical 0
saturation O 0
were O 0
monitored O 0
over O 0
1 O 0
hour O 0
. O 0

RESULTS O 0
: O 0
Three O 0
patients O 0
( O 0
8 O 0
. O 0
1 O 0
% O 0
) O 0
in O 0
the O 0
unilateral O 0
group O 0
and O 0
5 O 0
( O 0
13 O 0
. O 0
5 O 0
% O 0
) O 0
in O 0
the O 0
conventional O 0
group O 0
developed O 0
hypotension B-Disease 0
, O 0
P O 0
= O 0
0 O 0
. O 0
71 O 0
. O 0

Four O 0
( O 0
10 O 0
. O 0
8 O 0
% O 0
) O 0
patients O 0
in O 0
the O 0
conventional O 0
group O 0
and O 0
1 O 0
( O 0
2 O 0
. O 0
7 O 0
% O 0
) O 0
in O 0
the O 0
unilateral O 0
group O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
17 O 0
required O 0
epinephrine B-Chemical 0
infusion O 0
to O 0
treat O 0
hypotension B-Disease 0
. O 0

Patients O 0
in O 0
the O 0
conventional O 0
group O 0
had O 0
statistically O 0
significant O 0
greater O 0
fall O 0
in O 0
the O 0
systolic O 0
blood O 0
pressures O 0
at O 0
15 O 0
, O 0
30 O 0
and O 0
45 O 0
minutes O 0
when O 0
compared O 0
to O 0
the O 0
baseline O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
003 O 0
, O 0
0 O 0
. O 0
001 O 0
and O 0
0 O 0
. O 0
004 O 0
) O 0
. O 0

The O 0
mean O 0
respiratory O 0
rate O 0
and O 0
oxygen B-Chemical 0
saturations O 0
in O 0
the O 0
two O 0
groups O 0
were O 0
similar O 0
. O 0

CONCLUSION O 0
: O 0
Compared O 0
to O 0
conventional O 0
spinal O 0
anaesthesia O 0
, O 0
unilateral O 0
spinal O 0
anaesthesia O 0
was O 0
associated O 0
with O 0
fewer O 0
cardiovascular O 0
perturbations O 0
. O 0

Also O 0
, O 0
the O 0
type O 0
of O 0
spinal O 0
block O 0
instituted O 0
affected O 0
neither O 0
the O 0
respiratory O 0
rate O 0
nor O 0
the O 0
arterial O 0
oxygen B-Chemical 0
saturation O 0
. O 0

Spectrum O 0
of O 0
adverse O 0
events O 0
after O 0
generic O 0
HAART O 0
in O 0
southern O 0
Indian O 0
HIV B-Disease 0
- I-Disease 0
infected I-Disease 0
patients O 0
. O 0

To O 0
determine O 0
the O 0
incidence O 0
of O 0
clinically O 0
significant O 0
adverse O 0
events O 0
after O 0
long O 0
- O 0
term O 0
, O 0
fixed O 0
- O 0
dose O 0
, O 0
generic O 0
highly O 0
active O 0
antiretroviral O 0
therapy O 0
( O 0
HAART O 0
) O 0
use O 0
among O 0
HIV B-Disease 0
- I-Disease 0
infected I-Disease 0
individuals O 0
in O 0
South O 0
India O 0
, O 0
we O 0
examined O 0
the O 0
experiences O 0
of O 0
3154 O 0
HIV B-Disease 0
- I-Disease 0
infected I-Disease 0
individuals O 0
who O 0
received O 0
a O 0
minimum O 0
of O 0
3 O 0
months O 0
of O 0
generic O 0
HAART O 0
between O 0
February O 0
1996 O 0
and O 0
December O 0
2006 O 0
at O 0
a O 0
tertiary O 0
HIV O 0
care O 0
referral O 0
center O 0
in O 0
South O 0
India O 0
. O 0

The O 0
most O 0
common O 0
regimens O 0
were O 0
3TC B-Chemical 0
+ O 0
d4T B-Chemical 0
+ O 0
nevirapine B-Chemical 0
( O 0
NVP B-Chemical 0
) O 0
( O 0
54 O 0
. O 0
8 O 0
% O 0
) O 0
, O 0
zidovudine B-Chemical 0
( O 0
AZT B-Chemical 0
) O 0
+ O 0
3TC B-Chemical 0
+ O 0
NVP B-Chemical 0
( O 0
14 O 0
. O 0
5 O 0
% O 0
) O 0
, O 0
3TC B-Chemical 0
+ O 0
d4T B-Chemical 0
+ O 0
efavirenz B-Chemical 0
( O 0
EFV B-Chemical 0
) O 0
( O 0
20 O 0
. O 0
1 O 0
% O 0
) O 0
, O 0
and O 0
AZT B-Chemical 0
+ O 0
3TC B-Chemical 0
+ O 0
EFV B-Chemical 0
( O 0
5 O 0
. O 0
4 O 0
% O 0
) O 0
. O 0

The O 0
most O 0
common O 0
adverse O 0
events O 0
and O 0
median O 0
CD4 O 0
at O 0
time O 0
of O 0
event O 0
were O 0
rash B-Disease 0
( O 0
15 O 0
. O 0
2 O 0
% O 0
; O 0
CD4 O 0
, O 0
285 O 0
cells O 0
/ O 0
microL O 0
) O 0
and O 0
peripheral B-Disease 0
neuropathy I-Disease 0
( O 0
9 O 0
. O 0
0 O 0
% O 0
and O 0
348 O 0
cells O 0
/ O 0
microL O 0
) O 0
. O 0

Clinically O 0
significant O 0
anemia B-Disease 0
( O 0
hemoglobin O 0
< O 0
7 O 0
g O 0
/ O 0
dL O 0
) O 0
was O 0
observed O 0
in O 0
5 O 0
. O 0
4 O 0
% O 0
of O 0
patients O 0
( O 0
CD4 O 0
, O 0
165 O 0
cells O 0
/ O 0
microL O 0
) O 0
and O 0
hepatitis B-Disease 0
( O 0
clinical O 0
jaundice B-Disease 0
with O 0
alanine B-Chemical 0
aminotransferase O 0
> O 0
5 O 0
times O 0
upper O 0
limits O 0
of O 0
normal O 0
) O 0
in O 0
3 O 0
. O 0
5 O 0
% O 0
of O 0
patients O 0
( O 0
CD4 O 0
, O 0
260 O 0
cells O 0
/ O 0
microL O 0
) O 0
. O 0

Women O 0
were O 0
significantly O 0
more O 0
likely O 0
to O 0
experience O 0
lactic B-Disease 0
acidosis I-Disease 0
, O 0
while O 0
men O 0
were O 0
significantly O 0
more O 0
likely O 0
to O 0
experience O 0
immune B-Disease 0
reconstitution I-Disease 0
syndrome I-Disease 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Among O 0
the O 0
patients O 0
with O 0
1 O 0
year O 0
of O 0
follow O 0
- O 0
up O 0
, O 0
NVP B-Chemical 0
therapy O 0
was O 0
significantly O 0
associated O 0
with O 0
developing O 0
rash B-Disease 0
and O 0
d4T B-Chemical 0
therapy O 0
with O 0
developing O 0
peripheral B-Disease 0
neuropathy I-Disease 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Anemia B-Disease 0
and O 0
hepatitis B-Disease 0
often O 0
occur O 0
within O 0
12 O 0
weeks O 0
of O 0
initiating O 0
generic O 0
HAART O 0
. O 0

Frequent O 0
and O 0
early O 0
monitoring O 0
for O 0
these O 0
toxicities B-Disease 0
is O 0
warranted O 0
in O 0
developing O 0
countries O 0
where O 0
generic O 0
HAART O 0
is O 0
increasingly O 0
available O 0
. O 0

Thalidomide B-Chemical 0
and O 0
sensory B-Disease 0
neurotoxicity I-Disease 0
: O 0
a O 0
neurophysiological O 0
study O 0
. O 0

BACKGROUND O 0
: O 0
Recent O 0
studies O 0
confirmed O 0
a O 0
high O 0
incidence O 0
of O 0
sensory B-Disease 0
axonal I-Disease 0
neuropathy I-Disease 0
in O 0
patients O 0
treated O 0
with O 0
different O 0
doses O 0
of O 0
thalidomide B-Chemical 0
. O 0

The O 0
study O 0
' O 0
s O 0
aims O 0
were O 0
to O 0
measure O 0
variations O 0
in O 0
sural O 0
nerve O 0
sensory O 0
action O 0
potential O 0
( O 0
SAP O 0
) O 0
amplitude O 0
in O 0
patients O 0
with O 0
refractory O 0
cutaneous B-Disease 0
lupus I-Disease 0
erythematosus I-Disease 0
( O 0
CLE B-Disease 0
) O 0
treated O 0
with O 0
thalidomide B-Chemical 0
and O 0
use O 0
these O 0
findings O 0
to O 0
identify O 0
the O 0
neurotoxic B-Disease 0
potential O 0
of O 0
thalidomide B-Chemical 0
and O 0
the O 0
recovery O 0
capacity O 0
of O 0
sensory O 0
fibres O 0
after O 0
discontinuation O 0
of O 0
treatment O 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
Clinical O 0
and O 0
electrophysiological O 0
data O 0
in O 0
12 O 0
female O 0
patients O 0
with O 0
CLE B-Disease 0
during O 0
treatment O 0
with O 0
thalidomide B-Chemical 0
and O 0
up O 0
to O 0
47 O 0
months O 0
after O 0
discontinuation O 0
of O 0
treatment O 0
were O 0
analysed O 0
. O 0

Sural O 0
nerve O 0
SAP O 0
amplitude O 0
reduction O 0
> O 0
or O 0
= O 0
40 O 0
% O 0
was O 0
the O 0
criteria O 0
for O 0
discontinuing O 0
therapy O 0
. O 0

RESULTS O 0
: O 0
During O 0
treatment O 0
, O 0
11 O 0
patients O 0
showed O 0
a O 0
reduction O 0
in O 0
sural O 0
nerve O 0
SAP O 0
amplitude O 0
compared O 0
to O 0
baseline O 0
values O 0
( O 0
9 O 0
with O 0
a O 0
reduction O 0
> O 0
or O 0
= O 0
50 O 0
% O 0
and O 0
2 O 0
< O 0
50 O 0
% O 0
) O 0
. O 0

One O 0
patient O 0
showed O 0
no O 0
changes O 0
in O 0
SAP O 0
amplitude O 0
. O 0

Five O 0
patients O 0
complained O 0
of O 0
paresthesias B-Disease 0
and O 0
leg O 0
cramps B-Disease 0
. O 0

After O 0
thalidomide B-Chemical 0
treatment O 0
, O 0
sural O 0
SAP O 0
amplitude O 0
recovered O 0
in O 0
3 O 0
patients O 0
. O 0

At O 0
detection O 0
of O 0
reduction O 0
in O 0
sural O 0
nerve O 0
SAP O 0
amplitude O 0
, O 0
the O 0
median O 0
thalidomide B-Chemical 0
cumulative O 0
dose O 0
was O 0
21 O 0
. O 0
4 O 0
g O 0
. O 0

The O 0
threshold O 0
neurotoxic B-Disease 0
dosage O 0
is O 0
lower O 0
than O 0
previously O 0
reported O 0
. O 0

CONCLUSIONS O 0
: O 0
Sural O 0
nerve O 0
SAP O 0
amplitude O 0
reduction O 0
is O 0
a O 0
reliable O 0
and O 0
sensitive O 0
marker O 0
of O 0
degeneration O 0
and O 0
recovery O 0
of O 0
sensory O 0
fibres O 0
. O 0

This O 0
electrophysiological O 0
parameter O 0
provides O 0
information O 0
about O 0
subclinical O 0
neurotoxic B-Disease 0
potential O 0
of O 0
thalidomide B-Chemical 0
but O 0
is O 0
not O 0
helpful O 0
in O 0
predicting O 0
the O 0
appearance O 0
of O 0
sensory O 0
symptoms O 0
. O 0

Five O 0
cases O 0
of O 0
encephalitis B-Disease 0
during O 0
treatment O 0
of O 0
loiasis B-Disease 0
with O 0
diethylcarbamazine B-Chemical 0
. O 0

Five O 0
cases O 0
of O 0
encephalitis B-Disease 0
following O 0
treatment O 0
with O 0
diethylcarbamazine B-Chemical 0
( O 0
DEC B-Chemical 0
) O 0
were O 0
observed O 0
in O 0
Congolese O 0
patients O 0
with O 0
Loa O 0
loa O 0
filariasis B-Disease 0
. O 0

Two O 0
cases O 0
had O 0
a O 0
fatal O 0
outcome O 0
and O 0
one O 0
resulted O 0
in O 0
severe O 0
sequelae O 0
. O 0

The O 0
notable O 0
fact O 0
was O 0
that O 0
this O 0
complication O 0
occurred O 0
in O 0
three O 0
patients O 0
hospitalized O 0
before O 0
treatment O 0
began O 0
, O 0
with O 0
whom O 0
particularly O 0
strict O 0
therapeutic O 0
precautions O 0
were O 0
taken O 0
, O 0
i O 0
. O 0
e O 0
. O 0
, O 0
initial O 0
dose O 0
less O 0
than O 0
10 O 0
mg O 0
of O 0
DEC B-Chemical 0
, O 0
very O 0
gradual O 0
dose O 0
increases O 0
, O 0
and O 0
associated O 0
anti O 0
- O 0
allergic O 0
treatment O 0
. O 0

This O 0
type O 0
of O 0
drug O 0
- O 0
induced O 0
complication O 0
may O 0
not O 0
be O 0
that O 0
uncommon O 0
in O 0
highly O 0
endemic O 0
regions O 0
. O 0

It O 0
occurs O 0
primarily O 0
, O 0
but O 0
not O 0
exclusively O 0
, O 0
in O 0
subjects O 0
presenting O 0
with O 0
a O 0
high O 0
microfilarial O 0
load O 0
. O 0

The O 0
relationship O 0
between O 0
the O 0
occurrence O 0
of O 0
encephalitis B-Disease 0
and O 0
the O 0
decrease O 0
in O 0
microfilaremia B-Disease 0
is O 0
evident O 0
. O 0

The O 0
pathophysiological O 0
mechanisms O 0
are O 0
discussed O 0
in O 0
the O 0
light O 0
of O 0
these O 0
observations O 0
and O 0
the O 0
few O 0
other O 0
comments O 0
on O 0
this O 0
subject O 0
published O 0
in O 0
the O 0
literature O 0
. O 0

Amiodarone B-Chemical 0
- O 0
related O 0
pulmonary B-Disease 0
mass I-Disease 0
and O 0
unique O 0
membranous B-Disease 0
glomerulonephritis I-Disease 0
in O 0
a O 0
patient O 0
with O 0
valvular B-Disease 0
heart I-Disease 0
disease I-Disease 0
: O 0
Diagnostic O 0
pitfall O 0
and O 0
new O 0
findings O 0
. O 0

Amiodarone B-Chemical 0
is O 0
an O 0
anti O 0
- O 0
arrhythmic B-Disease 0
drug O 0
for O 0
life O 0
- O 0
threatening O 0
tachycardia B-Disease 0
, O 0
but O 0
various O 0
adverse O 0
effects O 0
have O 0
been O 0
reported O 0
. O 0

Reported O 0
herein O 0
is O 0
an O 0
autopsy O 0
case O 0
of O 0
valvular B-Disease 0
heart I-Disease 0
disease I-Disease 0
, O 0
in O 0
a O 0
patient O 0
who O 0
developed O 0
a O 0
lung B-Disease 0
mass I-Disease 0
( O 0
1 O 0
. O 0
5 O 0
cm O 0
in O 0
diameter O 0
) O 0
and O 0
proteinuria B-Disease 0
( O 0
2 O 0
. O 0
76 O 0
g O 0
/ O 0
day O 0
) O 0
after O 0
treatment O 0
with O 0
amiodarone B-Chemical 0
for O 0
a O 0
long O 0
time O 0
. O 0

The O 0
lung B-Disease 0
mass I-Disease 0
was O 0
highly O 0
suspected O 0
to O 0
be O 0
lung B-Disease 0
cancer I-Disease 0
on O 0
CT O 0
and O 0
positron O 0
emission O 0
tomography O 0
, O 0
but O 0
histologically O 0
the O 0
lesion O 0
was O 0
composed O 0
of O 0
lymphoplasmacytic O 0
infiltrates O 0
in O 0
alveolar O 0
walls O 0
and O 0
intra O 0
- O 0
alveolar O 0
accumulation O 0
of O 0
foamy O 0
macrophages O 0
containing O 0
characteristic O 0
myelinoid O 0
bodies O 0
, O 0
indicating O 0
that O 0
it O 0
was O 0
an O 0
amiodarone B-Chemical 0
- O 0
related O 0
lesion O 0
. O 0

In O 0
addition O 0
, O 0
the O 0
lung O 0
tissue O 0
had O 0
unevenly O 0
distributed O 0
hemosiderin B-Disease 0
deposition O 0
, O 0
and O 0
abnormally O 0
tortuous O 0
capillaries O 0
were O 0
seen O 0
in O 0
the O 0
mass O 0
and O 0
in O 0
heavily O 0
hemosiderotic B-Disease 0
lung O 0
portions O 0
outside O 0
the O 0
mass O 0
. O 0

In O 0
the O 0
kidneys O 0
, O 0
glomeruli O 0
had O 0
membrane O 0
spikes O 0
, O 0
prominent O 0
swelling O 0
of O 0
podocytes O 0
and O 0
subepithelial O 0
deposits O 0
, O 0
which O 0
were O 0
sometimes O 0
large O 0
and O 0
hump O 0
- O 0
like O 0
. O 0

Autoimmune B-Disease 0
diseases I-Disease 0
, O 0
viral B-Disease 0
hepatitis I-Disease 0
, O 0
malignant O 0
neoplasms B-Disease 0
or O 0
other O 0
diseases O 0
with O 0
a O 0
known O 0
relationship O 0
to O 0
membranous B-Disease 0
glomerulonephritis I-Disease 0
were O 0
not O 0
found O 0
. O 0

The O 0
present O 0
case O 0
highlights O 0
the O 0
possibility O 0
that O 0
differential O 0
diagnosis O 0
between O 0
an O 0
amiodarone B-Chemical 0
- O 0
related O 0
pulmonary B-Disease 0
lesion I-Disease 0
and O 0
a O 0
neoplasm B-Disease 0
can O 0
be O 0
very O 0
difficult O 0
radiologically O 0
, O 0
and O 0
suggests O 0
that O 0
membranous B-Disease 0
glomerulonephritis I-Disease 0
might O 0
be O 0
another O 0
possible O 0
complication O 0
of O 0
amiodarone B-Chemical 0
treatment O 0
. O 0

Risk O 0
of O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
associated O 0
with O 0
initial O 0
sulphonylurea B-Chemical 0
treatment O 0
of O 0
patients O 0
with O 0
type B-Disease 0
2 I-Disease 0
diabetes I-Disease 0
: O 0
a O 0
matched O 0
case O 0
- O 0
control O 0
study O 0
. O 0

AIMS O 0
: O 0
This O 0
study O 0
sought O 0
to O 0
assess O 0
the O 0
risk O 0
of O 0
developing O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
( O 0
CAD B-Disease 0
) O 0
associated O 0
with O 0
initial O 0
treatment O 0
of O 0
type B-Disease 0
2 I-Disease 0
diabetes I-Disease 0
with O 0
different O 0
sulphonylureas B-Chemical 0
. O 0

METHODS O 0
: O 0
In O 0
type B-Disease 0
2 I-Disease 0
diabetic I-Disease 0
patients O 0
, O 0
cases O 0
who O 0
developed O 0
CAD B-Disease 0
were O 0
compared O 0
retrospectively O 0
with O 0
controls O 0
that O 0
did O 0
not O 0
. O 0

The O 0
20 O 0
- O 0
year O 0
risk O 0
of O 0
CAD B-Disease 0
at O 0
diagnosis O 0
of O 0
diabetes B-Disease 0
, O 0
using O 0
the O 0
UKPDS O 0
risk O 0
engine O 0
, O 0
was O 0
used O 0
to O 0
match O 0
cases O 0
with O 0
controls O 0
. O 0

RESULTS O 0
: O 0
The O 0
76 O 0
cases O 0
of O 0
CAD B-Disease 0
were O 0
compared O 0
with O 0
152 O 0
controls O 0
. O 0

The O 0
hazard O 0
of O 0
developing O 0
CAD B-Disease 0
( O 0
95 O 0
% O 0
CI O 0
) O 0
associated O 0
with O 0
initial O 0
treatment O 0
increased O 0
by O 0
2 O 0
. O 0
4 O 0
- O 0
fold O 0
( O 0
1 O 0
. O 0
3 O 0
- O 0
4 O 0
. O 0
3 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
004 O 0
) O 0
with O 0
glibenclamide B-Chemical 0
; O 0
2 O 0
- O 0
fold O 0
( O 0
0 O 0
. O 0
9 O 0
- O 0
4 O 0
. O 0
6 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
099 O 0
) O 0
with O 0
glipizide B-Chemical 0
; O 0
2 O 0
. O 0
9 O 0
- O 0
fold O 0
( O 0
1 O 0
. O 0
6 O 0
- O 0
5 O 0
. O 0
1 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
000 O 0
) O 0
with O 0
either O 0
, O 0
and O 0
was O 0
unchanged O 0
with O 0
metformin B-Chemical 0
. O 0

The O 0
hazard O 0
decreased O 0
0 O 0
. O 0
3 O 0
- O 0
fold O 0
( O 0
0 O 0
. O 0
7 O 0
- O 0
1 O 0
. O 0
7 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
385 O 0
) O 0
with O 0
glimepiride B-Chemical 0
, O 0
0 O 0
. O 0
4 O 0
- O 0
fold O 0
( O 0
0 O 0
. O 0
7 O 0
- O 0
1 O 0
. O 0
3 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
192 O 0
) O 0
with O 0
gliclazide B-Chemical 0
, O 0
and O 0
0 O 0
. O 0
4 O 0
- O 0
fold O 0
( O 0
0 O 0
. O 0
7 O 0
- O 0
1 O 0
. O 0
1 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
09 O 0
) O 0
with O 0
either O 0
. O 0

CONCLUSIONS O 0
: O 0
Initiating O 0
treatment O 0
of O 0
type B-Disease 0
2 I-Disease 0
diabetes I-Disease 0
with O 0
glibenclamide B-Chemical 0
or O 0
glipizide B-Chemical 0
is O 0
associated O 0
with O 0
increased O 0
risk O 0
of O 0
CAD B-Disease 0
in O 0
comparison O 0
to O 0
gliclazide B-Chemical 0
or O 0
glimepiride B-Chemical 0
. O 0

If O 0
confirmed O 0
, O 0
this O 0
may O 0
be O 0
important O 0
because O 0
most O 0
Indian O 0
patients O 0
receive O 0
the O 0
cheaper O 0
older O 0
sulphonylureas B-Chemical 0
, O 0
and O 0
present O 0
guidelines O 0
do O 0
not O 0
distinguish O 0
between O 0
individual O 0
agents O 0
. O 0

Reduced O 0
progression O 0
of O 0
adriamycin B-Chemical 0
nephropathy B-Disease 0
in O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
treated O 0
by O 0
losartan B-Chemical 0
. O 0

BACKGROUND O 0
: O 0
The O 0
aim O 0
of O 0
the O 0
study O 0
was O 0
to O 0
investigate O 0
the O 0
antihypertensive O 0
effects O 0
of O 0
angiotensin B-Chemical 0
II I-Chemical 0
type O 0
- O 0
1 O 0
receptor O 0
blocker O 0
, O 0
losartan B-Chemical 0
, O 0
and O 0
its O 0
potential O 0
in O 0
slowing O 0
down O 0
renal B-Disease 0
disease I-Disease 0
progression O 0
in O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
( O 0
SHR O 0
) O 0
with O 0
adriamycin B-Chemical 0
( O 0
ADR B-Chemical 0
) O 0
nephropathy B-Disease 0
. O 0

METHODS O 0
: O 0
Six O 0
- O 0
month O 0
- O 0
old O 0
female O 0
SHR O 0
were O 0
randomly O 0
selected O 0
in O 0
six O 0
groups O 0
. O 0

Two O 0
control O 0
groups O 0
( O 0
SH O 0
( O 0
6 O 0
) O 0
, O 0
SH O 0
( O 0
12 O 0
) O 0
) O 0
received O 0
vehicle O 0
. O 0

Groups O 0
ADR B-Chemical 0
( O 0
6 O 0
) O 0
, O 0
ADR B-Chemical 0
+ O 0
LOS B-Chemical 0
( O 0
6 O 0
) O 0
and O 0
ADR B-Chemical 0
( O 0
12 O 0
) O 0
, O 0
and O 0
ADR B-Chemical 0
+ O 0
LOS B-Chemical 0
( O 0
12 O 0
) O 0
received O 0
ADR B-Chemical 0
( O 0
2 O 0
mg O 0
/ O 0
kg O 0
/ O 0
b O 0
. O 0
w O 0
. O 0
i O 0
. O 0
v O 0
. O 0
) O 0
twice O 0
in O 0
a O 0
3 O 0
- O 0
week O 0
interval O 0
. O 0

Group O 0
ADR B-Chemical 0
+ O 0
LOS B-Chemical 0
( O 0
6 O 0
) O 0
received O 0
losartan B-Chemical 0
( O 0
10 O 0
mg O 0
/ O 0
kg O 0
/ O 0
b O 0
. O 0
w O 0
. O 0
/ O 0
day O 0
by O 0
gavages O 0
) O 0
for O 0
6 O 0
weeks O 0
and O 0
group O 0
ADR B-Chemical 0
+ O 0
LOS B-Chemical 0
( O 0
12 O 0
) O 0
for O 0
12 O 0
weeks O 0
after O 0
second O 0
injection O 0
of O 0
ADR B-Chemical 0
. O 0

Animals O 0
were O 0
killed O 0
after O 0
6 O 0
or O 0
12 O 0
weeks O 0
, O 0
respectively O 0
. O 0

Haemodynamic O 0
measurements O 0
were O 0
performed O 0
on O 0
anaesthetized O 0
animals O 0
, O 0
blood O 0
and O 0
urine O 0
samples O 0
were O 0
taken O 0
for O 0
biochemical O 0
analysis O 0
and O 0
the O 0
left O 0
kidney O 0
was O 0
processed O 0
for O 0
morphological O 0
studies O 0
. O 0

RESULTS O 0
: O 0
Short O 0
- O 0
term O 0
losartan B-Chemical 0
treatment O 0
, O 0
besides O 0
antihypertensive O 0
effect O 0
, O 0
improved O 0
glomerular O 0
filtration O 0
rate O 0
and O 0
ameliorated O 0
glomerulosclerosis B-Disease 0
resulting O 0
in O 0
decreased O 0
proteinuria B-Disease 0
. O 0

Prolonged O 0
treatment O 0
with O 0
losartan B-Chemical 0
showed O 0
further O 0
reduction O 0
of O 0
glomerulosclerosis B-Disease 0
associated O 0
with O 0
reduced O 0
progression O 0
of O 0
tubular O 0
atrophy B-Disease 0
and O 0
interstitial B-Disease 0
fibrosis I-Disease 0
, O 0
thus O 0
preventing O 0
heavy O 0
proteinuria B-Disease 0
and O 0
chronic B-Disease 0
renal I-Disease 0
failure I-Disease 0
. O 0

Losartan B-Chemical 0
reduced O 0
uraemia B-Disease 0
and O 0
increased O 0
urea B-Chemical 0
clearance O 0
in O 0
advanced O 0
ADR B-Chemical 0
nephropathy B-Disease 0
in O 0
SHR O 0
. O 0

Histological O 0
examination O 0
showed O 0
that O 0
losartan B-Chemical 0
could O 0
prevent O 0
tubular O 0
atrophy B-Disease 0
, O 0
interstitial O 0
infiltration O 0
and O 0
fibrosis B-Disease 0
in O 0
ADR B-Chemical 0
nephropathy B-Disease 0
. O 0

CONCLUSION O 0
: O 0
Losartan B-Chemical 0
reduces O 0
the O 0
rate O 0
of O 0
progression O 0
of O 0
ADR B-Chemical 0
- O 0
induced O 0
focal B-Disease 0
segmental I-Disease 0
glomerulosclerosis I-Disease 0
to O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
renal I-Disease 0
disease I-Disease 0
in O 0
SHR O 0
. O 0

The O 0
risks O 0
of O 0
aprotinin O 0
and O 0
tranexamic B-Chemical 0
acid I-Chemical 0
in O 0
cardiac O 0
surgery O 0
: O 0
a O 0
one O 0
- O 0
year O 0
follow O 0
- O 0
up O 0
of O 0
1188 O 0
consecutive O 0
patients O 0
. O 0

BACKGROUND O 0
: O 0
Our O 0
aim O 0
was O 0
to O 0
investigate O 0
postoperative O 0
complications O 0
and O 0
mortality O 0
after O 0
administration O 0
of O 0
aprotinin O 0
compared O 0
to O 0
tranexamic B-Chemical 0
acid I-Chemical 0
in O 0
an O 0
unselected O 0
, O 0
consecutive O 0
cohort O 0
. O 0

METHODS O 0
: O 0
Perioperative O 0
data O 0
from O 0
consecutive O 0
cardiac O 0
surgery O 0
patients O 0
were O 0
prospectively O 0
collected O 0
between O 0
September O 0
2005 O 0
and O 0
June O 0
2006 O 0
in O 0
a O 0
university O 0
- O 0
affiliated O 0
clinic O 0
( O 0
n O 0
= O 0
1188 O 0
) O 0
. O 0

During O 0
the O 0
first O 0
5 O 0
mo O 0
, O 0
596 O 0
patients O 0
received O 0
aprotinin O 0
( O 0
Group O 0
A O 0
) O 0
; O 0
in O 0
the O 0
next O 0
5 O 0
mo O 0
, O 0
592 O 0
patients O 0
were O 0
treated O 0
with O 0
tranexamic B-Chemical 0
acid I-Chemical 0
( O 0
Group O 0
T O 0
) O 0
. O 0

Except O 0
for O 0
antifibrinolytic O 0
therapy O 0
, O 0
the O 0
anesthetic O 0
and O 0
surgical O 0
protocols O 0
remained O 0
unchanged O 0
. O 0

RESULTS O 0
: O 0
The O 0
pre O 0
- O 0
and O 0
intraoperative O 0
variables O 0
were O 0
comparable O 0
between O 0
the O 0
treatment O 0
groups O 0
. O 0

Postoperatively O 0
, O 0
a O 0
significantly O 0
higher O 0
incidence O 0
of O 0
seizures B-Disease 0
was O 0
found O 0
in O 0
Group O 0
T O 0
( O 0
4 O 0
. O 0
6 O 0
% O 0
vs O 0
1 O 0
. O 0
2 O 0
% O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

This O 0
difference O 0
was O 0
also O 0
significant O 0
in O 0
the O 0
primary O 0
valve O 0
surgery O 0
and O 0
the O 0
high O 0
risk O 0
surgery O 0
subgroups O 0
( O 0
7 O 0
. O 0
9 O 0
% O 0
vs O 0
1 O 0
. O 0
2 O 0
% O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
003 O 0
; O 0
7 O 0
. O 0
3 O 0
% O 0
vs O 0
2 O 0
. O 0
4 O 0
% O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
035 O 0
, O 0
respectively O 0
) O 0
. O 0

Persistent O 0
atrial O 0
fibrillation O 0
( O 0
7 O 0
. O 0
9 O 0
% O 0
vs O 0
2 O 0
. O 0
3 O 0
% O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
020 O 0
) O 0
and O 0
renal B-Disease 0
failure I-Disease 0
( O 0
9 O 0
. O 0
7 O 0
% O 0
vs O 0
1 O 0
. O 0
7 O 0
% O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
002 O 0
) O 0
were O 0
also O 0
more O 0
common O 0
in O 0
Group O 0
T O 0
, O 0
in O 0
the O 0
primary O 0
valve O 0
surgery O 0
subgroup O 0
. O 0

On O 0
the O 0
contrary O 0
, O 0
among O 0
primary O 0
coronary O 0
artery O 0
bypass O 0
surgery O 0
patients O 0
, O 0
there O 0
were O 0
more O 0
acute O 0
myocardial B-Disease 0
infarctions I-Disease 0
and O 0
renal B-Disease 0
dysfunction I-Disease 0
in O 0
Group O 0
A O 0
( O 0
5 O 0
. O 0
8 O 0
% O 0
vs O 0
2 O 0
. O 0
0 O 0
% O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
027 O 0
; O 0
22 O 0
. O 0
5 O 0
% O 0
vs O 0
15 O 0
. O 0
2 O 0
% O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
036 O 0
, O 0
respectively O 0
) O 0
. O 0

The O 0
1 O 0
- O 0
yr O 0
mortality O 0
was O 0
significantly O 0
higher O 0
after O 0
aprotinin O 0
treatment O 0
in O 0
the O 0
high O 0
risk O 0
surgery O 0
group O 0
( O 0
17 O 0
. O 0
7 O 0
% O 0
vs O 0
9 O 0
. O 0
8 O 0
% O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
034 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
Both O 0
antifibrinolytic O 0
drugs O 0
bear O 0
the O 0
risk O 0
of O 0
adverse O 0
outcome O 0
depending O 0
on O 0
the O 0
type O 0
of O 0
cardiac O 0
surgery O 0
. O 0

Administration O 0
of O 0
aprotinin O 0
should O 0
be O 0
avoided O 0
in O 0
coronary O 0
artery O 0
bypass O 0
graft O 0
and O 0
high O 0
risk O 0
patients O 0
, O 0
whereas O 0
administration O 0
of O 0
tranexamic B-Chemical 0
acid I-Chemical 0
is O 0
not O 0
recommended O 0
in O 0
valve O 0
surgery O 0
. O 0

Delirium B-Disease 0
in O 0
an O 0
elderly O 0
woman O 0
possibly O 0
associated O 0
with O 0
administration O 0
of O 0
misoprostol B-Chemical 0
. O 0

Misoprostol B-Chemical 0
has O 0
been O 0
associated O 0
with O 0
adverse O 0
reactions O 0
, O 0
including O 0
gastrointestinal O 0
symptoms O 0
, O 0
gynecologic O 0
problems O 0
, O 0
and O 0
headache B-Disease 0
. O 0

Changes O 0
in O 0
mental O 0
status O 0
, O 0
however O 0
, O 0
have O 0
not O 0
been O 0
reported O 0
. O 0

We O 0
present O 0
a O 0
case O 0
in O 0
which O 0
an O 0
89 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
in O 0
a O 0
long O 0
- O 0
term O 0
care O 0
facility O 0
became O 0
confused O 0
after O 0
the O 0
initiation O 0
of O 0
misoprostol B-Chemical 0
therapy O 0
. O 0

The O 0
patient O 0
' O 0
s O 0
change O 0
in O 0
mental O 0
status O 0
was O 0
first O 0
reported O 0
nine O 0
days O 0
after O 0
the O 0
initiation O 0
of O 0
therapy O 0
. O 0

Her O 0
delirium B-Disease 0
significantly O 0
improved O 0
after O 0
misoprostol B-Chemical 0
was O 0
discontinued O 0
and O 0
her O 0
mental O 0
status O 0
returned O 0
to O 0
normal O 0
within O 0
a O 0
week O 0
. O 0

Because O 0
no O 0
other O 0
factors O 0
related O 0
to O 0
this O 0
patient O 0
changed O 0
significantly O 0
, O 0
the O 0
delirium B-Disease 0
experienced O 0
by O 0
this O 0
patient O 0
possibly O 0
resulted O 0
from O 0
misoprostol B-Chemical 0
therapy O 0
. O 0

The O 0
biological O 0
properties O 0
of O 0
the O 0
optical O 0
isomers O 0
of O 0
propranolol B-Chemical 0
and O 0
their O 0
effects O 0
on O 0
cardiac B-Disease 0
arrhythmias I-Disease 0
. O 0

1 O 0
. O 0

The O 0
optical O 0
isomers O 0
of O 0
propranolol B-Chemical 0
have O 0
been O 0
compared O 0
for O 0
their O 0
beta O 0
- O 0
blocking O 0
and O 0
antiarrhythmic O 0
activities O 0
. O 0
2 O 0
. O 0

In O 0
blocking O 0
the O 0
positive O 0
inotropic O 0
and O 0
chronotropic O 0
responses O 0
to O 0
isoprenaline B-Chemical 0
, O 0
( O 0
+ O 0
) O 0
- O 0
propranolol B-Chemical 0
had O 0
less O 0
than O 0
one O 0
hundredth O 0
the O 0
potency O 0
of O 0
( O 0
- O 0
) O 0
- O 0
propranolol B-Chemical 0
. O 0

At O 0
dose O 0
levels O 0
of O 0
( O 0
+ O 0
) O 0
- O 0
propranolol B-Chemical 0
which O 0
attenuated O 0
the O 0
responses O 0
to O 0
isoprenaline B-Chemical 0
, O 0
there O 0
was O 0
a O 0
significant O 0
prolongation O 0
of O 0
the O 0
PR O 0
interval O 0
of O 0
the O 0
electrocardiogram O 0
. O 0
3 O 0
. O 0

The O 0
metabolic O 0
responses O 0
to O 0
isoprenaline B-Chemical 0
in O 0
dogs O 0
( O 0
an O 0
increase O 0
in O 0
circulating O 0
glucose B-Chemical 0
, O 0
lactate B-Chemical 0
and O 0
free O 0
fatty B-Chemical 0
acids I-Chemical 0
) O 0
were O 0
all O 0
blocked O 0
by O 0
( O 0
- O 0
) O 0
- O 0
propranolol B-Chemical 0
. O 0

( O 0
+ O 0
) O 0
- O 0
Propranolol B-Chemical 0
had O 0
no O 0
effect O 0
on O 0
fatty B-Chemical 0
acid I-Chemical 0
mobilization O 0
but O 0
significantly O 0
reduced O 0
the O 0
increments O 0
in O 0
both O 0
lactate B-Chemical 0
and O 0
glucose B-Chemical 0
. O 0
4 O 0
. O 0

Both O 0
isomers O 0
of O 0
propranolol B-Chemical 0
possessed O 0
similar O 0
depressant O 0
potency O 0
on O 0
isolated O 0
atrial O 0
muscle O 0
taken O 0
from O 0
guinea O 0
- O 0
pigs O 0
. O 0
5 O 0
. O 0

The O 0
isomers O 0
of O 0
propranolol B-Chemical 0
exhibited O 0
similar O 0
local O 0
anaesthetic O 0
potencies O 0
on O 0
an O 0
isolated O 0
frog O 0
nerve O 0
preparation O 0
at O 0
a O 0
level O 0
approximately O 0
three O 0
times O 0
that O 0
of O 0
procaine B-Chemical 0
. O 0

The O 0
racemic O 0
compound O 0
was O 0
significantly O 0
less O 0
potent O 0
than O 0
either O 0
isomer O 0
. O 0
6 O 0
. O 0

Both O 0
isomers O 0
of O 0
propranolol B-Chemical 0
were O 0
capable O 0
of O 0
preventing O 0
adrenaline B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
arrhythmias I-Disease 0
in O 0
cats O 0
anaesthetized O 0
with O 0
halothane B-Chemical 0
, O 0
but O 0
the O 0
mean O 0
dose O 0
of O 0
( O 0
- O 0
) O 0
- O 0
propranolol B-Chemical 0
was O 0
0 O 0
. O 0
09 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
02 O 0
mg O 0
/ O 0
kg O 0
whereas O 0
that O 0
of O 0
( O 0
+ O 0
) O 0
- O 0
propranolol B-Chemical 0
was O 0
4 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
2 O 0
mg O 0
/ O 0
kg O 0
. O 0

At O 0
the O 0
effective O 0
dose O 0
level O 0
of O 0
( O 0
+ O 0
) O 0
- O 0
propranolol B-Chemical 0
there O 0
was O 0
a O 0
significant O 0
prolongation O 0
of O 0
the O 0
PR O 0
interval O 0
of O 0
the O 0
electrocardiogram O 0
. O 0

Blockade O 0
of O 0
arrhythmias B-Disease 0
with O 0
both O 0
isomers O 0
was O 0
surmountable O 0
by O 0
increasing O 0
the O 0
dose O 0
of O 0
adrenaline B-Chemical 0
. O 0
7 O 0
. O 0

Both O 0
isomers O 0
of O 0
propranolol B-Chemical 0
were O 0
also O 0
capable O 0
of O 0
reversing O 0
ventricular B-Disease 0
tachycardia I-Disease 0
caused O 0
by O 0
ouabain B-Chemical 0
in O 0
anaesthetized O 0
cats O 0
and O 0
dogs O 0
. O 0

The O 0
dose O 0
of O 0
( O 0
- O 0
) O 0
- O 0
propranolol B-Chemical 0
was O 0
significantly O 0
smaller O 0
than O 0
that O 0
of O 0
( O 0
+ O 0
) O 0
- O 0
propranolol B-Chemical 0
in O 0
both O 0
species O 0
but O 0
much O 0
higher O 0
than O 0
that O 0
required O 0
to O 0
produce O 0
evidence O 0
of O 0
beta O 0
- O 0
blockade O 0
. O 0
8 O 0
. O 0

The O 0
implications O 0
of O 0
these O 0
results O 0
are O 0
discussed O 0
. O 0

Topotecan B-Chemical 0
in O 0
combination O 0
with O 0
radiotherapy O 0
in O 0
unresectable O 0
glioblastoma B-Disease 0
: O 0
a O 0
phase O 0
2 O 0
study O 0
. O 0

Improving O 0
glioblastoma B-Disease 0
multiforme I-Disease 0
( O 0
GBM B-Disease 0
) O 0
treatment O 0
with O 0
radio O 0
- O 0
chemotherapy O 0
remains O 0
a O 0
challenge O 0
. O 0

Topotecan B-Chemical 0
is O 0
an O 0
attractive O 0
option O 0
as O 0
it O 0
exhibits O 0
growth O 0
inhibition O 0
of O 0
human O 0
glioma B-Disease 0
as O 0
well O 0
as O 0
brain O 0
penetration O 0
. O 0

The O 0
present O 0
study O 0
assessed O 0
the O 0
combination O 0
of O 0
radiotherapy O 0
( O 0
60 O 0
Gy O 0
/ O 0
30 O 0
fractions O 0
/ O 0
40 O 0
days O 0
) O 0
and O 0
topotecan B-Chemical 0
( O 0
0 O 0
. O 0
9 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
/ O 0
day O 0
on O 0
days O 0
1 O 0
- O 0
5 O 0
on O 0
weeks O 0
1 O 0
, O 0
3 O 0
and O 0
5 O 0
) O 0
in O 0
50 O 0
adults O 0
with O 0
histologically O 0
proven O 0
and O 0
untreated O 0
GBM B-Disease 0
. O 0

The O 0
incidence O 0
of O 0
non O 0
- O 0
hematological O 0
toxicities B-Disease 0
was O 0
low O 0
and O 0
grade O 0
3 O 0
- O 0
4 O 0
hematological O 0
toxicities B-Disease 0
were O 0
reported O 0
in O 0
20 O 0
patients O 0
( O 0
mainly O 0
lymphopenia B-Disease 0
and O 0
neutropenia B-Disease 0
) O 0
. O 0

Partial O 0
response O 0
and O 0
stabilization O 0
rates O 0
were O 0
2 O 0
% O 0
and O 0
32 O 0
% O 0
, O 0
respectively O 0
, O 0
with O 0
an O 0
overall O 0
time O 0
to O 0
progression O 0
of O 0
12 O 0
weeks O 0
. O 0

One O 0
- O 0
year O 0
overall O 0
survival O 0
( O 0
OS O 0
) O 0
rate O 0
was O 0
42 O 0
% O 0
, O 0
with O 0
a O 0
median O 0
OS O 0
of O 0
40 O 0
weeks O 0
. O 0

Topotecan B-Chemical 0
in O 0
combination O 0
with O 0
radiotherapy O 0
was O 0
well O 0
tolerated O 0
. O 0

However O 0
, O 0
while O 0
response O 0
and O 0
stabilization O 0
concerned O 0
one O 0
- O 0
third O 0
of O 0
the O 0
patients O 0
, O 0
the O 0
study O 0
did O 0
not O 0
show O 0
increased O 0
benefits O 0
in O 0
terms O 0
of O 0
survival O 0
in O 0
patients O 0
with O 0
unresectable O 0
GBM B-Disease 0
. O 0

Long O 0
- O 0
term O 0
lithium B-Chemical 0
therapy O 0
leading O 0
to O 0
hyperparathyroidism B-Disease 0
: O 0
a O 0
case O 0
report O 0
. O 0

PURPOSE O 0
: O 0
This O 0
paper O 0
reviews O 0
the O 0
effect O 0
of O 0
chronic O 0
lithium B-Chemical 0
therapy O 0
on O 0
serum O 0
calcium B-Chemical 0
level O 0
and O 0
parathyroid O 0
glands O 0
, O 0
its O 0
pathogenesis O 0
, O 0
and O 0
treatment O 0
options O 0
. O 0

We O 0
examined O 0
the O 0
case O 0
of O 0
a O 0
lithium B-Chemical 0
- O 0
treated O 0
patient O 0
who O 0
had O 0
recurrent O 0
hypercalcemia B-Disease 0
to O 0
better O 0
understand O 0
the O 0
disease O 0
process O 0
. O 0

CONCLUSION O 0
: O 0
Primary B-Disease 0
hyperparathyroidism I-Disease 0
is O 0
a O 0
rare O 0
but O 0
potentially O 0
life O 0
- O 0
threatening O 0
side O 0
effect O 0
of O 0
long O 0
- O 0
term O 0
lithium B-Chemical 0
therapy O 0
. O 0

Careful O 0
patient O 0
selection O 0
and O 0
long O 0
- O 0
term O 0
follow O 0
- O 0
up O 0
can O 0
reduce O 0
morbidity O 0
. O 0

PRACTICAL O 0
IMPLICATIONS O 0
: O 0
As O 0
much O 0
as O 0
15 O 0
% O 0
of O 0
lithium B-Chemical 0
- O 0
treated O 0
patients O 0
become O 0
hypercalcemic B-Disease 0
. O 0

By O 0
routinely O 0
monitoring O 0
serum O 0
calcium B-Chemical 0
levels O 0
, O 0
healthcare O 0
providers O 0
can O 0
improve O 0
the O 0
quality O 0
of O 0
life O 0
of O 0
this O 0
patient O 0
group O 0
. O 0

Comparison O 0
of O 0
laryngeal O 0
mask O 0
with O 0
endotracheal O 0
tube O 0
for O 0
anesthesia O 0
in O 0
endoscopic O 0
sinus O 0
surgery O 0
. O 0

BACKGROUND O 0
: O 0
The O 0
purpose O 0
of O 0
this O 0
study O 0
was O 0
to O 0
compare O 0
surgical O 0
conditions O 0
, O 0
including O 0
the O 0
amount O 0
of O 0
intraoperative O 0
bleeding B-Disease 0
as O 0
well O 0
as O 0
intraoperative O 0
blood O 0
pressure O 0
, O 0
during O 0
functional O 0
endoscopic O 0
sinus O 0
surgery O 0
( O 0
FESS O 0
) O 0
using O 0
flexible O 0
reinforced O 0
laryngeal O 0
mask O 0
airway O 0
( O 0
FRLMA O 0
) O 0
versus O 0
endotracheal O 0
tube O 0
( O 0
ETT O 0
) O 0
in O 0
maintaining O 0
controlled O 0
hypotension B-Disease 0
anesthesia O 0
induced O 0
by O 0
propofol B-Chemical 0
- O 0
remifentanil B-Chemical 0
total O 0
i O 0
. O 0
v O 0
. O 0
anesthesia O 0
( O 0
TIVA O 0
) O 0
. O 0

METHODS O 0
: O 0
Sixty O 0
normotensive O 0
American O 0
Society O 0
of O 0
Anesthesiologists O 0
I O 0
- O 0
II O 0
adult O 0
patients O 0
undergoing O 0
FESS O 0
under O 0
controlled O 0
hypotension B-Disease 0
anesthesia O 0
caused O 0
by O 0
propofol B-Chemical 0
- O 0
remifentanil B-Chemical 0
- O 0
TIVA O 0
were O 0
randomly O 0
assigned O 0
into O 0
two O 0
groups O 0
: O 0
group O 0
I O 0
, O 0
FRLMA O 0
; O 0
group O 0
II O 0
, O 0
ETT O 0
. O 0

Hemorrhage B-Disease 0
was O 0
measured O 0
and O 0
the O 0
visibility O 0
of O 0
the O 0
operative O 0
field O 0
was O 0
evaluated O 0
according O 0
to O 0
a O 0
six O 0
- O 0
point O 0
scale O 0
. O 0

RESULTS O 0
: O 0
Controlled O 0
hypotension B-Disease 0
was O 0
achieved O 0
within O 0
a O 0
shorter O 0
period O 0
using O 0
laryngeal O 0
mask O 0
using O 0
lower O 0
rates O 0
of O 0
remifentanil B-Chemical 0
infusion O 0
and O 0
lower O 0
total O 0
dose O 0
of O 0
remifentanil B-Chemical 0
. O 0

CONCLUSION O 0
: O 0
In O 0
summary O 0
, O 0
our O 0
results O 0
indicate O 0
that O 0
airway O 0
management O 0
using O 0
FRLMA O 0
during O 0
controlled O 0
hypotension B-Disease 0
anesthesia O 0
provided O 0
better O 0
surgical O 0
conditions O 0
in O 0
terms O 0
of O 0
quality O 0
of O 0
operative O 0
field O 0
and O 0
blood O 0
loss O 0
and O 0
allowed O 0
for O 0
convenient O 0
induced O 0
hypotension B-Disease 0
with O 0
low O 0
doses O 0
of O 0
remifentanil B-Chemical 0
during O 0
TIVA O 0
in O 0
patients O 0
undergoing O 0
FESS O 0
. O 0

Nonalcoholic B-Disease 0
fatty I-Disease 0
liver I-Disease 0
disease I-Disease 0
during O 0
valproate B-Chemical 0
therapy O 0
. O 0

Valproic B-Chemical 0
acid I-Chemical 0
( O 0
VPA B-Chemical 0
) O 0
is O 0
effective O 0
for O 0
the O 0
treatment O 0
of O 0
many O 0
types O 0
of O 0
epilepsy B-Disease 0
, O 0
but O 0
its O 0
use O 0
can O 0
be O 0
associated O 0
with O 0
an O 0
increase O 0
in O 0
body O 0
weight O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
nonalcoholic B-Disease 0
fatty I-Disease 0
liver I-Disease 0
disease I-Disease 0
( O 0
NAFLD B-Disease 0
) O 0
arising O 0
in O 0
a O 0
child O 0
who O 0
developed O 0
obesity B-Disease 0
during O 0
VPA B-Chemical 0
treatment O 0
. O 0

Laboratory O 0
data O 0
revealed O 0
hyperinsulinemia B-Disease 0
with O 0
insulin B-Disease 0
resistance I-Disease 0
. O 0

After O 0
the O 0
withdrawal O 0
of O 0
VPA B-Chemical 0
therapy O 0
, O 0
our O 0
patient O 0
showed O 0
a O 0
significant O 0
weight B-Disease 0
loss I-Disease 0
, O 0
a O 0
decrease O 0
of O 0
body O 0
mass O 0
index O 0
, O 0
and O 0
normalization O 0
of O 0
metabolic O 0
and O 0
endocrine O 0
parameters O 0
; O 0
moreover O 0
, O 0
ultrasound O 0
measurements O 0
showed O 0
a O 0
complete O 0
normalization O 0
. O 0

The O 0
present O 0
case O 0
suggests O 0
that O 0
obesity B-Disease 0
, O 0
hyperinsulinemia B-Disease 0
, O 0
insulin B-Disease 0
resistance I-Disease 0
, O 0
and O 0
long O 0
- O 0
term O 0
treatment O 0
with O 0
VPA B-Chemical 0
may O 0
be O 0
all O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
NAFLD B-Disease 0
; O 0
this O 0
side O 0
effect O 0
is O 0
reversible O 0
after O 0
VPA B-Chemical 0
withdrawal O 0
. O 0

Carbimazole B-Chemical 0
induced O 0
ANCA B-Disease 0
positive I-Disease 0
vasculitis I-Disease 0
. O 0

Anti B-Chemical 0
- I-Chemical 0
thyroid I-Chemical 0
drugs I-Chemical 0
, O 0
like O 0
carbimazole B-Chemical 0
and O 0
propylthiouracil B-Chemical 0
( O 0
PTU B-Chemical 0
) O 0
are O 0
commonly O 0
prescribed O 0
for O 0
the O 0
treatment O 0
of O 0
hyperthyroidism B-Disease 0
. O 0

One O 0
should O 0
be O 0
aware O 0
of O 0
the O 0
side O 0
effects O 0
of O 0
antithyroid B-Chemical 0
medications I-Chemical 0
. O 0

Antineutrophil B-Disease 0
cytoplasmic I-Disease 0
antibody I-Disease 0
( I-Disease 0
ANCA I-Disease 0
) I-Disease 0
- I-Disease 0
- I-Disease 0
associated I-Disease 0
vasculitis I-Disease 0
is O 0
a O 0
potentially O 0
life O 0
- O 0
threatening O 0
adverse O 0
effect O 0
of O 0
antithyroidmedications B-Chemical 0
. O 0

We O 0
report O 0
a O 0
patient O 0
with O 0
Graves B-Disease 0
' I-Disease 0
disease I-Disease 0
who O 0
developed O 0
ANCA O 0
positive O 0
carbimazole B-Chemical 0
induced O 0
vasculitis B-Disease 0
. O 0

The O 0
episode O 0
was O 0
characterized O 0
by O 0
a O 0
vasculitic B-Disease 0
skin B-Disease 0
rash I-Disease 0
associated O 0
with O 0
large O 0
joint O 0
arthritis B-Disease 0
, O 0
pyrexia B-Disease 0
and O 0
parotiditis B-Disease 0
but O 0
no O 0
renal O 0
or O 0
pulmonary O 0
involvement O 0
. O 0

He O 0
was O 0
referred O 0
to O 0
us O 0
for O 0
neurological O 0
evaluation O 0
because O 0
he O 0
had O 0
difficulty O 0
in O 0
getting O 0
up O 0
from O 0
squatting O 0
position O 0
and O 0
was O 0
suspected O 0
to O 0
have O 0
myositis B-Disease 0
. O 0

Carbimazole B-Chemical 0
and O 0
methimazole B-Chemical 0
have O 0
a O 0
lower O 0
incidence O 0
of O 0
reported O 0
ANCA O 0
positive O 0
side O 0
effects O 0
than O 0
PUT O 0
. O 0

To O 0
the O 0
best O 0
of O 0
our O 0
knowledge O 0
this O 0
is O 0
the O 0
first O 0
ANCA O 0
positive O 0
carbimazole B-Chemical 0
induced O 0
vasculitis B-Disease 0
case O 0
reported O 0
from O 0
India O 0
. O 0

Aspirin B-Chemical 0
for O 0
the O 0
primary O 0
prevention O 0
of O 0
cardiovascular O 0
events O 0
: O 0
an O 0
update O 0
of O 0
the O 0
evidence O 0
for O 0
the O 0
U O 0
. O 0
S O 0
. O 0

Preventive O 0
Services O 0
Task O 0
Force O 0
. O 0

BACKGROUND O 0
: O 0
Coronary B-Disease 0
heart I-Disease 0
disease I-Disease 0
and O 0
cerebrovascular B-Disease 0
disease I-Disease 0
are O 0
leading O 0
causes O 0
of O 0
death O 0
in O 0
the O 0
United O 0
States O 0
. O 0

In O 0
2002 O 0
, O 0
the O 0
U O 0
. O 0
S O 0
. O 0

Preventive O 0
Services O 0
Task O 0
Force O 0
( O 0
USPSTF O 0
) O 0
strongly O 0
recommended O 0
that O 0
clinicians O 0
discuss O 0
aspirin B-Chemical 0
with O 0
adults O 0
who O 0
are O 0
at O 0
increased O 0
risk O 0
for O 0
coronary B-Disease 0
heart I-Disease 0
disease I-Disease 0
. O 0

PURPOSE O 0
: O 0
To O 0
determine O 0
the O 0
benefits O 0
and O 0
harms O 0
of O 0
taking O 0
aspirin B-Chemical 0
for O 0
the O 0
primary O 0
prevention O 0
of O 0
myocardial B-Disease 0
infarctions I-Disease 0
, O 0
strokes B-Disease 0
, O 0
and O 0
death O 0
. O 0

DATA O 0
SOURCES O 0
: O 0
MEDLINE O 0
and O 0
Cochrane O 0
Library O 0
( O 0
search O 0
dates O 0
, O 0
1 O 0
January O 0
2001 O 0
to O 0
28 O 0
August O 0
2008 O 0
) O 0
, O 0
recent O 0
systematic O 0
reviews O 0
, O 0
reference O 0
lists O 0
of O 0
retrieved O 0
articles O 0
, O 0
and O 0
suggestions O 0
from O 0
experts O 0
. O 0

STUDY O 0
SELECTION O 0
: O 0
English O 0
- O 0
language O 0
randomized O 0
, O 0
controlled O 0
trials O 0
( O 0
RCTs O 0
) O 0
; O 0
case O 0
- O 0
control O 0
studies O 0
; O 0
meta O 0
- O 0
analyses O 0
; O 0
and O 0
systematic O 0
reviews O 0
of O 0
aspirin B-Chemical 0
versus O 0
control O 0
for O 0
the O 0
primary O 0
prevention O 0
of O 0
cardiovascular B-Disease 0
disease I-Disease 0
( O 0
CVD B-Disease 0
) O 0
were O 0
selected O 0
to O 0
answer O 0
the O 0
following O 0
questions O 0
: O 0
Does O 0
aspirin B-Chemical 0
decrease O 0
coronary O 0
heart O 0
events O 0
, O 0
strokes B-Disease 0
, O 0
death O 0
from O 0
coronary O 0
heart O 0
events O 0
or O 0
stroke B-Disease 0
, O 0
or O 0
all O 0
- O 0
cause O 0
mortality O 0
in O 0
adults O 0
without O 0
known O 0
CVD B-Disease 0
? O 0

Does O 0
aspirin B-Chemical 0
increase O 0
gastrointestinal B-Disease 0
bleeding I-Disease 0
or O 0
hemorrhagic B-Disease 0
strokes I-Disease 0
? O 0

DATA O 0
EXTRACTION O 0
: O 0
All O 0
studies O 0
were O 0
reviewed O 0
, O 0
abstracted O 0
, O 0
and O 0
rated O 0
for O 0
quality O 0
by O 0
using O 0
predefined O 0
USPSTF O 0
criteria O 0
. O 0

DATA O 0
SYNTHESIS O 0
: O 0
New O 0
evidence O 0
from O 0
1 O 0
good O 0
- O 0
quality O 0
RCT O 0
, O 0
1 O 0
good O 0
- O 0
quality O 0
meta O 0
- O 0
analysis O 0
, O 0
and O 0
2 O 0
fair O 0
- O 0
quality O 0
subanalyses O 0
of O 0
RCTs O 0
demonstrates O 0
that O 0
aspirin B-Chemical 0
use O 0
reduces O 0
the O 0
number O 0
of O 0
CVD B-Disease 0
events O 0
in O 0
patients O 0
without O 0
known O 0
CVD B-Disease 0
. O 0

Men O 0
in O 0
these O 0
studies O 0
experienced O 0
fewer O 0
myocardial B-Disease 0
infarctions I-Disease 0
and O 0
women O 0
experienced O 0
fewer O 0
ischemic O 0
strokes B-Disease 0
. O 0

Aspirin B-Chemical 0
does O 0
not O 0
seem O 0
to O 0
affect O 0
CVD B-Disease 0
mortality O 0
or O 0
all O 0
- O 0
cause O 0
mortality O 0
in O 0
either O 0
men O 0
or O 0
women O 0
. O 0

The O 0
use O 0
of O 0
aspirin B-Chemical 0
for O 0
primary O 0
prevention O 0
increases O 0
the O 0
risk O 0
for O 0
major O 0
bleeding B-Disease 0
events O 0
, O 0
primarily O 0
gastrointestinal B-Disease 0
bleeding I-Disease 0
events O 0
, O 0
in O 0
both O 0
men O 0
and O 0
women O 0
. O 0

Men O 0
have O 0
an O 0
increased O 0
risk O 0
for O 0
hemorrhagic B-Disease 0
strokes I-Disease 0
with O 0
aspirin B-Chemical 0
use O 0
. O 0

A O 0
new O 0
RCT O 0
and O 0
meta O 0
- O 0
analysis O 0
suggest O 0
that O 0
the O 0
risk O 0
for O 0
hemorrhagic B-Disease 0
strokes I-Disease 0
in O 0
women O 0
is O 0
not O 0
statistically O 0
significantly O 0
increased O 0
. O 0

LIMITATIONS O 0
: O 0
New O 0
evidence O 0
on O 0
aspirin B-Chemical 0
for O 0
the O 0
primary O 0
prevention O 0
of O 0
CVD B-Disease 0
is O 0
limited O 0
. O 0

The O 0
dose O 0
of O 0
aspirin B-Chemical 0
used O 0
in O 0
the O 0
RCTs O 0
varied O 0
, O 0
which O 0
prevented O 0
the O 0
estimation O 0
of O 0
the O 0
most O 0
appropriate O 0
dose O 0
for O 0
primary O 0
prevention O 0
. O 0

Several O 0
of O 0
the O 0
RCTs O 0
were O 0
conducted O 0
within O 0
populations O 0
of O 0
health O 0
professionals O 0
, O 0
which O 0
potentially O 0
limits O 0
generalizability O 0
. O 0

CONCLUSION O 0
: O 0
Aspirin B-Chemical 0
reduces O 0
the O 0
risk O 0
for O 0
myocardial B-Disease 0
infarction I-Disease 0
in O 0
men O 0
and O 0
strokes B-Disease 0
in O 0
women O 0
. O 0

Aspirin B-Chemical 0
use O 0
increases O 0
the O 0
risk O 0
for O 0
serious O 0
bleeding B-Disease 0
events O 0
. O 0

Reducing O 0
harm O 0
associated O 0
with O 0
anticoagulation O 0
: O 0
practical O 0
considerations O 0
of O 0
argatroban B-Chemical 0
therapy O 0
in O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
. O 0

Argatroban B-Chemical 0
is O 0
a O 0
hepatically O 0
metabolized O 0
, O 0
direct O 0
thrombin O 0
inhibitor O 0
used O 0
for O 0
prophylaxis O 0
or O 0
treatment O 0
of O 0
thrombosis B-Disease 0
in O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
( O 0
HIT B-Disease 0
) O 0
and O 0
for O 0
patients O 0
with O 0
or O 0
at O 0
risk O 0
of O 0
HIT B-Disease 0
undergoing O 0
percutaneous O 0
coronary O 0
intervention O 0
( O 0
PCI O 0
) O 0
. O 0

The O 0
objective O 0
of O 0
this O 0
review O 0
is O 0
to O 0
summarize O 0
practical O 0
considerations O 0
of O 0
argatroban B-Chemical 0
therapy O 0
in O 0
HIT B-Disease 0
. O 0

The O 0
US O 0
FDA O 0
- O 0
recommended O 0
argatroban B-Chemical 0
dose O 0
in O 0
HIT B-Disease 0
is O 0
2 O 0
microg O 0
/ O 0
kg O 0
/ O 0
min O 0
( O 0
reduced O 0
in O 0
patients O 0
with O 0
hepatic B-Disease 0
impairment I-Disease 0
and O 0
in O 0
paediatric O 0
patients O 0
) O 0
, O 0
adjusted O 0
to O 0
achieve O 0
activated O 0
partial O 0
thromboplastin O 0
times O 0
( O 0
aPTTs O 0
) O 0
1 O 0
. O 0
5 O 0
- O 0
3 O 0
times O 0
baseline O 0
( O 0
not O 0
> O 0
100 O 0
seconds O 0
) O 0
. O 0

Contemporary O 0
experiences O 0
indicate O 0
that O 0
reduced O 0
doses O 0
are O 0
also O 0
needed O 0
in O 0
patients O 0
with O 0
conditions O 0
associated O 0
with O 0
hepatic O 0
hypoperfusion O 0
, O 0
e O 0
. O 0
g O 0
. O 0
heart B-Disease 0
failure I-Disease 0
, O 0
yet O 0
are O 0
unnecessary O 0
for O 0
renal B-Disease 0
dysfunction I-Disease 0
, O 0
adult O 0
age O 0
, O 0
sex O 0
, O 0
race O 0
/ O 0
ethnicity O 0
or O 0
obesity B-Disease 0
. O 0

Argatroban B-Chemical 0
0 O 0
. O 0
5 O 0
- O 0
1 O 0
. O 0
2 O 0
microg O 0
/ O 0
kg O 0
/ O 0
min O 0
typically O 0
supports O 0
therapeutic O 0
aPTTs O 0
. O 0

The O 0
FDA O 0
- O 0
recommended O 0
dose O 0
during O 0
PCI O 0
is O 0
25 O 0
microg O 0
/ O 0
kg O 0
/ O 0
min O 0
( O 0
350 O 0
microg O 0
/ O 0
kg O 0
initial O 0
bolus O 0
) O 0
, O 0
adjusted O 0
to O 0
achieve O 0
activated O 0
clotting O 0
times O 0
( O 0
ACTs O 0
) O 0
of O 0
300 O 0
- O 0
450 O 0
sec O 0
. O 0

For O 0
PCI O 0
, O 0
argatroban B-Chemical 0
has O 0
not O 0
been O 0
investigated O 0
in O 0
hepatically O 0
impaired O 0
patients O 0
; O 0
dose O 0
adjustment O 0
is O 0
unnecessary O 0
for O 0
adult O 0
age O 0
, O 0
sex O 0
, O 0
race O 0
/ O 0
ethnicity O 0
or O 0
obesity B-Disease 0
, O 0
and O 0
lesser O 0
doses O 0
may O 0
be O 0
adequate O 0
with O 0
concurrent O 0
glycoprotein O 0
IIb O 0
/ O 0
IIIa O 0
inhibition O 0
. O 0

Argatroban B-Chemical 0
prolongs O 0
the O 0
International O 0
Normalized O 0
Ratio O 0
, O 0
and O 0
published O 0
approaches O 0
for O 0
monitoring O 0
the O 0
argatroban B-Chemical 0
- O 0
to O 0
- O 0
warfarin B-Chemical 0
transition O 0
should O 0
be O 0
followed O 0
. O 0

Major O 0
bleeding B-Disease 0
with O 0
argatroban B-Chemical 0
is O 0
0 O 0
- O 0
10 O 0
% O 0
in O 0
the O 0
non O 0
- O 0
interventional O 0
setting O 0
and O 0
0 O 0
- O 0
5 O 0
. O 0
8 O 0
% O 0
periprocedurally O 0
. O 0

Argatroban B-Chemical 0
has O 0
no O 0
specific O 0
antidote O 0
, O 0
and O 0
if O 0
excessive O 0
anticoagulation O 0
occurs O 0
, O 0
argatroban B-Chemical 0
infusion O 0
should O 0
be O 0
stopped O 0
or O 0
reduced O 0
. O 0

Improved O 0
familiarity O 0
of O 0
healthcare O 0
professionals O 0
with O 0
argatroban B-Chemical 0
therapy O 0
in O 0
HIT B-Disease 0
, O 0
including O 0
in O 0
special O 0
populations O 0
and O 0
during O 0
PCI O 0
, O 0
may O 0
facilitate O 0
reduction O 0
of O 0
harm O 0
associated O 0
with O 0
HIT B-Disease 0
( O 0
e O 0
. O 0
g O 0
. O 0
fewer O 0
thromboses O 0
) O 0
or O 0
its O 0
treatment O 0
( O 0
e O 0
. O 0
g O 0
. O 0
fewer O 0
argatroban B-Chemical 0
medication O 0
errors O 0
) O 0
. O 0

Rhabdomyolysis B-Disease 0
and O 0
brain O 0
ischemic B-Disease 0
stroke I-Disease 0
in O 0
a O 0
heroin B-Chemical 0
- O 0
dependent O 0
male O 0
under O 0
methadone B-Chemical 0
maintenance O 0
therapy O 0
. O 0

OBJECTIVE O 0
: O 0
There O 0
are O 0
several O 0
complications O 0
associated O 0
with O 0
heroin B-Disease 0
abuse I-Disease 0
, O 0
some O 0
of O 0
which O 0
are O 0
life O 0
- O 0
threatening O 0
. O 0

Methadone B-Chemical 0
may O 0
aggravate O 0
this O 0
problem O 0
. O 0

METHOD O 0
: O 0
A O 0
clinical O 0
case O 0
description O 0
. O 0

RESULTS O 0
: O 0
A O 0
33 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
presented O 0
with O 0
rhabdomyolysis B-Disease 0
and O 0
cerebral O 0
ischemic B-Disease 0
stroke I-Disease 0
after O 0
intravenous O 0
heroin B-Chemical 0
. O 0

He O 0
had O 0
used O 0
heroin B-Chemical 0
since O 0
age O 0
20 O 0
, O 0
and O 0
had O 0
used O 0
150 O 0
mg O 0
methadone B-Chemical 0
daily O 0
for O 0
6 O 0
months O 0
. O 0

He O 0
was O 0
found O 0
unconsciousness B-Disease 0
at O 0
home O 0
and O 0
was O 0
sent O 0
to O 0
our O 0
hospital O 0
. O 0

In O 0
the O 0
ER O 0
, O 0
his O 0
opiate O 0
level O 0
was O 0
4497 O 0
ng O 0
/ O 0
ml O 0
. O 0

In O 0
the O 0
ICU O 0
, O 0
we O 0
found O 0
rhabdomyolysis B-Disease 0
, O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
and O 0
acute O 0
respiratory B-Disease 0
failure I-Disease 0
. O 0

After O 0
transfer O 0
to O 0
an O 0
internal O 0
ward O 0
, O 0
we O 0
noted O 0
aphasia B-Disease 0
and O 0
weakness B-Disease 0
of O 0
his O 0
left O 0
limbs O 0
. O 0

After O 0
MRI O 0
, O 0
we O 0
found O 0
cerebral B-Disease 0
ischemic I-Disease 0
infarction I-Disease 0
. O 0

CONCLUSION O 0
: O 0
Those O 0
using O 0
methadone B-Chemical 0
and O 0
heroin B-Chemical 0
simultaneously O 0
may O 0
increase O 0
risk O 0
of O 0
rhabdomyolysis B-Disease 0
and O 0
ischemic B-Disease 0
stroke I-Disease 0
. O 0

Patients O 0
under O 0
methadone B-Chemical 0
maintenance O 0
therapy O 0
should O 0
be O 0
warned O 0
regarding O 0
these O 0
serious O 0
adverse O 0
events O 0
. O 0

Hypotheses O 0
of O 0
heroin B-Chemical 0
- O 0
related O 0
rhabdomyolysis B-Disease 0
and O 0
stroke B-Disease 0
in O 0
heroin B-Chemical 0
abusers O 0
are O 0
discussed O 0
. O 0

Increased O 0
vulnerability O 0
to O 0
6 B-Chemical 0
- I-Chemical 0
hydroxydopamine I-Chemical 0
lesion O 0
and O 0
reduced O 0
development O 0
of O 0
dyskinesias B-Disease 0
in O 0
mice O 0
lacking O 0
CB1 O 0
cannabinoid O 0
receptors O 0
. O 0

Motor O 0
impairment O 0
, O 0
dopamine B-Chemical 0
( O 0
DA B-Chemical 0
) O 0
neuronal O 0
activity O 0
and O 0
proenkephalin B-Chemical 0
( O 0
PENK B-Chemical 0
) O 0
gene O 0
expression O 0
in O 0
the O 0
caudate O 0
- O 0
putamen O 0
( O 0
CPu O 0
) O 0
were O 0
measured O 0
in O 0
6 B-Chemical 0
- I-Chemical 0
OHDA I-Chemical 0
- O 0
lesioned O 0
and O 0
treated O 0
( O 0
L B-Chemical 0
- I-Chemical 0
DOPA I-Chemical 0
+ I-Chemical 0
benserazide I-Chemical 0
) O 0
CB1 O 0
KO O 0
and O 0
WT O 0
mice O 0
. O 0

A O 0
lesion O 0
induced O 0
by O 0
6 B-Chemical 0
- I-Chemical 0
OHDA I-Chemical 0
produced O 0
more O 0
severe O 0
motor O 0
deterioration O 0
in O 0
CB1 O 0
KO O 0
mice O 0
accompanied O 0
by O 0
more O 0
loss O 0
of O 0
DA B-Chemical 0
neurons O 0
and O 0
increased O 0
PENK B-Chemical 0
gene O 0
expression O 0
in O 0
the O 0
CPu O 0
. O 0

Oxidative O 0
/ O 0
nitrosative O 0
and O 0
neuroinflammatory O 0
parameters O 0
were O 0
estimated O 0
in O 0
the O 0
CPu O 0
and O 0
cingulate O 0
cortex O 0
( O 0
Cg O 0
) O 0
. O 0

CB1 O 0
KO O 0
mice O 0
exhibited O 0
higher O 0
MDA B-Chemical 0
levels O 0
and O 0
iNOS O 0
protein O 0
expression O 0
in O 0
the O 0
CPu O 0
and O 0
Cg O 0
compared O 0
to O 0
WT O 0
mice O 0
. O 0

Treatment O 0
with O 0
L B-Chemical 0
- I-Chemical 0
DOPA I-Chemical 0
+ I-Chemical 0
benserazide I-Chemical 0
( O 0
12 O 0
weeks O 0
) O 0
resulted O 0
in O 0
less O 0
severe O 0
dyskinesias B-Disease 0
in O 0
CB1 O 0
KO O 0
than O 0
in O 0
WT O 0
mice O 0
. O 0

The O 0
results O 0
revealed O 0
that O 0
the O 0
lack O 0
of O 0
cannabinoid O 0
CB1 O 0
receptors O 0
increased O 0
the O 0
severity O 0
of O 0
motor O 0
impairment O 0
and O 0
DA B-Chemical 0
lesion O 0
, O 0
and O 0
reduced O 0
L B-Chemical 0
- I-Chemical 0
DOPA I-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
activation O 0
of O 0
CB1 O 0
receptors O 0
offers O 0
neuroprotection O 0
against O 0
dopaminergic O 0
lesion O 0
and O 0
the O 0
development O 0
of O 0
L B-Chemical 0
- I-Chemical 0
DOPA I-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
. O 0

Hepatocellular O 0
oxidant O 0
stress O 0
following O 0
intestinal O 0
ischemia B-Disease 0
- O 0
reperfusion B-Disease 0
injury I-Disease 0
. O 0

Reperfusion O 0
of O 0
ischemic B-Disease 0
intestine O 0
results O 0
in O 0
acute O 0
liver B-Disease 0
dysfunction I-Disease 0
characterized O 0
by O 0
hepatocellular O 0
enzyme O 0
release O 0
into O 0
plasma O 0
, O 0
reduction O 0
in O 0
bile O 0
flow O 0
rate O 0
, O 0
and O 0
neutrophil O 0
sequestration O 0
within O 0
the O 0
liver O 0
. O 0

The O 0
pathophysiology O 0
underlying O 0
this O 0
acute O 0
hepatic B-Disease 0
injury I-Disease 0
is O 0
unknown O 0
. O 0

This O 0
study O 0
was O 0
undertaken O 0
to O 0
determine O 0
whether O 0
oxidants O 0
are O 0
associated O 0
with O 0
the O 0
hepatic B-Disease 0
injury I-Disease 0
and O 0
to O 0
determine O 0
the O 0
relative O 0
value O 0
of O 0
several O 0
indirect O 0
methods O 0
of O 0
assessing O 0
oxidant O 0
exposure O 0
in O 0
vivo O 0
. O 0

Rats O 0
were O 0
subjected O 0
to O 0
a O 0
standardized O 0
intestinal O 0
ischemia B-Disease 0
- O 0
reperfusion B-Disease 0
injury I-Disease 0
. O 0

Hepatic O 0
tissue O 0
was O 0
assayed O 0
for O 0
lipid O 0
peroxidation O 0
products O 0
and O 0
oxidized B-Chemical 0
and I-Chemical 0
reduced I-Chemical 0
glutathione I-Chemical 0
. O 0

There O 0
was O 0
no O 0
change O 0
in O 0
hepatic O 0
tissue O 0
total O 0
glutathione B-Chemical 0
following O 0
intestinal O 0
ischemia B-Disease 0
- O 0
reperfusion B-Disease 0
injury I-Disease 0
. O 0

Oxidized B-Chemical 0
glutathione I-Chemical 0
( O 0
GSSG B-Chemical 0
) O 0
increased O 0
significantly O 0
following O 0
30 O 0
and O 0
60 O 0
min O 0
of O 0
reperfusion O 0
. O 0

There O 0
was O 0
no O 0
increase O 0
in O 0
any O 0
of O 0
the O 0
products O 0
of O 0
lipid O 0
peroxidation O 0
associated O 0
with O 0
this O 0
injury O 0
. O 0

An O 0
increase O 0
in O 0
GSSG B-Chemical 0
within O 0
hepatic O 0
tissue O 0
during O 0
intestinal O 0
reperfusion O 0
suggests O 0
exposure O 0
of O 0
hepatocytes O 0
to O 0
an O 0
oxidant O 0
stress O 0
. O 0

The O 0
lack O 0
of O 0
a O 0
significant O 0
increase O 0
in O 0
products O 0
of O 0
lipid O 0
peroxidation O 0
suggests O 0
that O 0
the O 0
oxidant O 0
stress O 0
is O 0
of O 0
insufficient O 0
magnitude O 0
to O 0
result O 0
in O 0
irreversible O 0
injury O 0
to O 0
hepatocyte O 0
cell O 0
membranes O 0
. O 0

These O 0
data O 0
also O 0
suggest O 0
that O 0
the O 0
measurement O 0
of O 0
tissue O 0
GSSG B-Chemical 0
may O 0
be O 0
a O 0
more O 0
sensitive O 0
indicator O 0
of O 0
oxidant O 0
stress O 0
than O 0
measurement O 0
of O 0
products O 0
of O 0
lipid O 0
peroxidation O 0
. O 0

Animal O 0
model O 0
of O 0
mania B-Disease 0
induced O 0
by O 0
ouabain B-Chemical 0
: O 0
Evidence O 0
of O 0
oxidative O 0
stress O 0
in O 0
submitochondrial O 0
particles O 0
of O 0
the O 0
rat O 0
brain O 0
. O 0

The O 0
intracerebroventricular O 0
( O 0
ICV O 0
) O 0
administration O 0
of O 0
ouabain B-Chemical 0
( O 0
a O 0
Na B-Chemical 0
( O 0
+ O 0
) O 0
/ O 0
K B-Chemical 0
( O 0
+ O 0
) O 0
- O 0
ATPase O 0
inhibitor O 0
) O 0
in O 0
rats O 0
has O 0
been O 0
suggested O 0
to O 0
mimic O 0
some O 0
symptoms O 0
of O 0
human O 0
bipolar B-Disease 0
mania I-Disease 0
. O 0

Clinical O 0
studies O 0
have O 0
shown O 0
that O 0
bipolar B-Disease 0
disorder I-Disease 0
may O 0
be O 0
related O 0
to O 0
mitochondrial B-Disease 0
dysfunction I-Disease 0
. O 0

Herein O 0
, O 0
we O 0
investigated O 0
the O 0
behavioral O 0
and O 0
biochemical O 0
effects O 0
induced O 0
by O 0
the O 0
ICV O 0
administration O 0
of O 0
ouabain B-Chemical 0
in O 0
rats O 0
. O 0

To O 0
achieve O 0
this O 0
aim O 0
, O 0
the O 0
effects O 0
of O 0
ouabain B-Chemical 0
injection O 0
immediately O 0
after O 0
and O 0
7 O 0
days O 0
following O 0
a O 0
single O 0
ICV O 0
administration O 0
( O 0
at O 0
concentrations O 0
of O 0
10 O 0
( O 0
- O 0
2 O 0
) O 0
and O 0
10 O 0
( O 0
- O 0
3 O 0
) O 0
M O 0
) O 0
on O 0
locomotion O 0
was O 0
measured O 0
using O 0
the O 0
open O 0
- O 0
field O 0
test O 0
. O 0

Additionally O 0
, O 0
thiobarbituric B-Chemical 0
acid I-Chemical 0
reactive O 0
substances O 0
( O 0
TBARSs O 0
) O 0
and O 0
superoxide B-Chemical 0
production O 0
were O 0
measured O 0
in O 0
submitochondrial O 0
particles O 0
of O 0
the O 0
prefrontal O 0
cortex O 0
, O 0
hippocampus O 0
, O 0
striatum O 0
and O 0
amygdala O 0
. O 0

Our O 0
findings O 0
demonstrated O 0
that O 0
ouabain B-Chemical 0
at O 0
10 O 0
( O 0
- O 0
2 O 0
) O 0
and O 0
10 O 0
( O 0
- O 0
3 O 0
) O 0
M O 0
induced O 0
hyperlocomotion B-Disease 0
in O 0
rats O 0
, O 0
and O 0
this O 0
response O 0
remained O 0
up O 0
to O 0
7 O 0
days O 0
following O 0
a O 0
single O 0
ICV O 0
injection O 0
. O 0

In O 0
addition O 0
, O 0
we O 0
observed O 0
that O 0
the O 0
persistent O 0
increase O 0
in O 0
the O 0
rat O 0
spontaneous O 0
locomotion O 0
is O 0
associated O 0
with O 0
increased O 0
TBARS O 0
levels O 0
and O 0
superoxide B-Chemical 0
generation O 0
in O 0
submitochondrial O 0
particles O 0
in O 0
the O 0
prefrontal O 0
cortex O 0
, O 0
striatum O 0
and O 0
amygdala O 0
. O 0

In O 0
conclusion O 0
, O 0
ouabain B-Chemical 0
- O 0
induced O 0
mania B-Disease 0
- O 0
like O 0
behavior O 0
may O 0
provide O 0
a O 0
useful O 0
animal O 0
model O 0
to O 0
test O 0
the O 0
hypothesis O 0
of O 0
the O 0
involvement O 0
of O 0
oxidative O 0
stress O 0
in O 0
bipolar B-Disease 0
disorder I-Disease 0
. O 0

Intraoperative O 0
dialysis O 0
during O 0
liver O 0
transplantation O 0
with O 0
citrate B-Chemical 0
dialysate O 0
. O 0

Liver O 0
transplantation O 0
for O 0
acutely O 0
ill O 0
patients O 0
with O 0
fulminant B-Disease 0
liver I-Disease 0
failure I-Disease 0
carries O 0
high O 0
intraoperative O 0
and O 0
immediate O 0
postoperative O 0
risks O 0
. O 0

These O 0
are O 0
increased O 0
with O 0
the O 0
presence O 0
of O 0
concomitant O 0
acute B-Disease 0
kidney I-Disease 0
injury I-Disease 0
( O 0
AKI B-Disease 0
) O 0
and O 0
intraoperative O 0
dialysis O 0
is O 0
sometimes O 0
required O 0
to O 0
allow O 0
the O 0
transplant O 0
to O 0
proceed O 0
. O 0

The O 0
derangements O 0
in O 0
the O 0
procoagulant O 0
and O 0
anticoagulant O 0
pathways O 0
during O 0
fulminant B-Disease 0
liver I-Disease 0
failure I-Disease 0
can O 0
lead O 0
to O 0
difficulties O 0
with O 0
anticoagulation O 0
during O 0
dialysis O 0
, O 0
especially O 0
when O 0
continued O 0
in O 0
the O 0
operating O 0
room O 0
. O 0

Systemic O 0
anticoagulation O 0
is O 0
unsafe O 0
and O 0
regional O 0
citrate B-Chemical 0
anticoagulation O 0
in O 0
the O 0
absence O 0
of O 0
a O 0
functional O 0
liver O 0
carries O 0
the O 0
risk O 0
of O 0
citrate B-Chemical 0
toxicity B-Disease 0
. O 0

Citrate B-Chemical 0
dialysate O 0
, O 0
a O 0
new O 0
dialysate O 0
with O 0
citric B-Chemical 0
acid I-Chemical 0
can O 0
be O 0
used O 0
for O 0
anticoagulation O 0
in O 0
patients O 0
who O 0
cannot O 0
tolerate O 0
heparin B-Chemical 0
or O 0
regional O 0
citrate B-Chemical 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
a O 0
40 O 0
- O 0
year O 0
- O 0
old O 0
female O 0
with O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
fulminant B-Disease 0
liver I-Disease 0
failure I-Disease 0
with O 0
associated O 0
AKI B-Disease 0
who O 0
underwent O 0
intraoperative O 0
dialytic O 0
support O 0
during O 0
liver O 0
transplantation O 0
anticoagulated O 0
with O 0
citrate B-Chemical 0
dialysate O 0
during O 0
the O 0
entire O 0
procedure O 0
. O 0

The O 0
patient O 0
tolerated O 0
the O 0
procedure O 0
well O 0
without O 0
any O 0
signs O 0
of O 0
citrate B-Chemical 0
toxicity B-Disease 0
and O 0
maintained O 0
adequate O 0
anticoagulation O 0
for O 0
patency O 0
of O 0
the O 0
dialysis O 0
circuit O 0
. O 0

Citrate B-Chemical 0
dialysate O 0
is O 0
a O 0
safe O 0
alternative O 0
for O 0
intradialytic O 0
support O 0
of O 0
liver O 0
transplantation O 0
in O 0
fulminant B-Disease 0
liver I-Disease 0
failure I-Disease 0
. O 0

Delirium B-Disease 0
in O 0
a O 0
patient O 0
with O 0
toxic O 0
flecainide B-Chemical 0
plasma O 0
concentrations O 0
: O 0
the O 0
role O 0
of O 0
a O 0
pharmacokinetic O 0
drug O 0
interaction O 0
with O 0
paroxetine B-Chemical 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
describe O 0
a O 0
case O 0
of O 0
flecainide B-Chemical 0
- O 0
induced O 0
delirium B-Disease 0
associated O 0
with O 0
a O 0
pharmacokinetic O 0
drug O 0
interaction O 0
with O 0
paroxetine B-Chemical 0
. O 0

CASE O 0
SUMMARY O 0
: O 0
A O 0
69 O 0
- O 0
year O 0
- O 0
old O 0
white O 0
female O 0
presented O 0
to O 0
the O 0
emergency O 0
department O 0
with O 0
a O 0
history O 0
of O 0
confusion B-Disease 0
and O 0
paranoia B-Disease 0
over O 0
the O 0
past O 0
several O 0
days O 0
. O 0

On O 0
admission O 0
the O 0
patient O 0
was O 0
taking O 0
carvedilol B-Chemical 0
12 O 0
mg O 0
twice O 0
daily O 0
, O 0
warfarin B-Chemical 0
2 O 0
mg O 0
/ O 0
day O 0
, O 0
folic B-Chemical 0
acid I-Chemical 0
1 O 0
mg O 0
/ O 0
day O 0
, O 0
levothyroxine B-Chemical 0
100 O 0
microg O 0
/ O 0
day O 0
, O 0
pantoprazole B-Chemical 0
40 O 0
mg O 0
/ O 0
day O 0
, O 0
paroxetine B-Chemical 0
40 O 0
mg O 0
/ O 0
day O 0
, O 0
and O 0
flecainide B-Chemical 0
100 O 0
mg O 0
twice O 0
daily O 0
. O 0

Flecainide B-Chemical 0
had O 0
been O 0
started O 0
2 O 0
weeks O 0
prior O 0
for O 0
atrial B-Disease 0
fibrillation I-Disease 0
. O 0

Laboratory O 0
test O 0
findings O 0
on O 0
admission O 0
were O 0
notable O 0
only O 0
for O 0
a O 0
flecainide B-Chemical 0
plasma O 0
concentration O 0
of O 0
1360 O 0
microg O 0
/ O 0
L O 0
( O 0
reference O 0
range O 0
200 O 0
- O 0
1000 O 0
) O 0
. O 0

A O 0
metabolic O 0
drug O 0
interaction O 0
between O 0
flecainide B-Chemical 0
and O 0
paroxetine B-Chemical 0
, O 0
which O 0
the O 0
patient O 0
had O 0
been O 0
taking O 0
for O 0
more O 0
than O 0
5 O 0
years O 0
, O 0
was O 0
considered O 0
. O 0

Paroxetine B-Chemical 0
was O 0
discontinued O 0
and O 0
the O 0
dose O 0
of O 0
flecainide B-Chemical 0
was O 0
reduced O 0
to O 0
50 O 0
mg O 0
twice O 0
daily O 0
. O 0

Her O 0
delirium B-Disease 0
resolved O 0
3 O 0
days O 0
later O 0
. O 0

DISCUSSION O 0
: O 0
Flecainide B-Chemical 0
and O 0
pharmacologically O 0
similar O 0
agents O 0
that O 0
interact O 0
with O 0
sodium B-Chemical 0
channels O 0
may O 0
cause O 0
delirium B-Disease 0
in O 0
susceptible O 0
patients O 0
. O 0

A O 0
MEDLINE O 0
search O 0
( O 0
1966 O 0
- O 0
January O 0
2009 O 0
) O 0
revealed O 0
one O 0
in O 0
vivo O 0
pharmacokinetic O 0
study O 0
on O 0
the O 0
interaction O 0
between O 0
flecainide B-Chemical 0
, O 0
a O 0
CYP2D6 O 0
substrate O 0
, O 0
and O 0
paroxetine B-Chemical 0
, O 0
a O 0
CYP2D6 O 0
inhibitor O 0
, O 0
as O 0
well O 0
as O 0
3 O 0
case O 0
reports O 0
of O 0
flecainide B-Chemical 0
- O 0
induced O 0
delirium B-Disease 0
. O 0

According O 0
to O 0
the O 0
Naranjo O 0
probability O 0
scale O 0
, O 0
flecainide B-Chemical 0
was O 0
the O 0
probable O 0
cause O 0
of O 0
the O 0
patient O 0
' O 0
s O 0
delirium B-Disease 0
; O 0
the O 0
Horn O 0
Drug O 0
Interaction O 0
Probability O 0
Scale O 0
indicates O 0
a O 0
possible O 0
pharmacokinetic O 0
drug O 0
interaction O 0
between O 0
flecainide B-Chemical 0
and O 0
paroxetine B-Chemical 0
. O 0

CONCLUSIONS O 0
: O 0
Supratherapeutic O 0
flecainide B-Chemical 0
plasma O 0
concentrations O 0
may O 0
cause O 0
delirium B-Disease 0
. O 0

Because O 0
toxicity B-Disease 0
may O 0
occur O 0
when O 0
flecainide B-Chemical 0
is O 0
prescribed O 0
with O 0
paroxetine B-Chemical 0
and O 0
other O 0
potent O 0
CYP2D6 O 0
inhibitors O 0
, O 0
flecainide B-Chemical 0
plasma O 0
concentrations O 0
should O 0
be O 0
monitored O 0
closely O 0
with O 0
commencement O 0
of O 0
CYP2D6 O 0
inhibitors O 0
. O 0

Efficacy O 0
of O 0
everolimus B-Chemical 0
( O 0
RAD001 B-Chemical 0
) O 0
in O 0
patients O 0
with O 0
advanced O 0
NSCLC B-Disease 0
previously O 0
treated O 0
with O 0
chemotherapy O 0
alone O 0
or O 0
with O 0
chemotherapy O 0
and O 0
EGFR O 0
inhibitors O 0
. O 0

BACKGROUND O 0
: O 0
Treatment O 0
options O 0
are O 0
scarce O 0
in O 0
pretreated O 0
advanced O 0
non B-Disease 0
- I-Disease 0
small I-Disease 0
- I-Disease 0
cell I-Disease 0
lung I-Disease 0
cancer I-Disease 0
( O 0
NSCLC B-Disease 0
) O 0
patients O 0
. O 0

RAD001 B-Chemical 0
, O 0
an O 0
oral O 0
inhibitor O 0
of O 0
the O 0
mammalian O 0
target O 0
of O 0
rapamycin B-Chemical 0
( O 0
mTOR O 0
) O 0
, O 0
has O 0
shown O 0
phase O 0
I O 0
efficacy O 0
in O 0
NSCLC B-Disease 0
. O 0

METHODS O 0
: O 0
Stage O 0
IIIb O 0
or O 0
IV O 0
NSCLC B-Disease 0
patients O 0
, O 0
with O 0
two O 0
or O 0
fewer O 0
prior O 0
chemotherapy O 0
regimens O 0
, O 0
one O 0
platinum B-Chemical 0
based O 0
( O 0
stratum O 0
1 O 0
) O 0
or O 0
both O 0
chemotherapy O 0
and O 0
epidermal O 0
growth O 0
factor O 0
receptor O 0
tyrosine B-Chemical 0
kinase O 0
inhibitors O 0
( O 0
stratum O 0
2 O 0
) O 0
, O 0
received O 0
RAD001 B-Chemical 0
10 O 0
mg O 0
/ O 0
day O 0
until O 0
progression O 0
or O 0
unacceptable O 0
toxicity B-Disease 0
. O 0

Primary O 0
objective O 0
was O 0
overall O 0
response O 0
rate O 0
( O 0
ORR O 0
) O 0
. O 0

Analyses O 0
of O 0
markers O 0
associated O 0
with O 0
the O 0
mTOR O 0
pathway O 0
were O 0
carried O 0
out O 0
on O 0
archival O 0
tumor B-Disease 0
from O 0
a O 0
subgroup O 0
using O 0
immunohistochemistry O 0
( O 0
IHC O 0
) O 0
and O 0
direct O 0
mutation O 0
sequencing O 0
. O 0

RESULTS O 0
: O 0
Eighty O 0
- O 0
five O 0
patients O 0
were O 0
enrolled O 0
, O 0
42 O 0
in O 0
stratum O 0
1 O 0
and O 0
43 O 0
in O 0
stratum O 0
. O 0

ORR O 0
was O 0
4 O 0
. O 0
7 O 0
% O 0
( O 0
7 O 0
. O 0
1 O 0
% O 0
stratum O 0
1 O 0
; O 0
2 O 0
. O 0
3 O 0
% O 0
stratum O 0
2 O 0
) O 0
. O 0

Overall O 0
disease O 0
control O 0
rate O 0
was O 0
47 O 0
. O 0
1 O 0
% O 0
. O 0

Median O 0
progression O 0
- O 0
free O 0
survivals O 0
( O 0
PFSs O 0
) O 0
were O 0
2 O 0
. O 0
6 O 0
( O 0
stratum O 0
1 O 0
) O 0
and O 0
2 O 0
. O 0
7 O 0
months O 0
( O 0
stratum O 0
2 O 0
) O 0
. O 0

Common O 0
> O 0
or O 0
= O 0
grade O 0
3 O 0
events O 0
were O 0
fatigue B-Disease 0
, O 0
dyspnea B-Disease 0
, O 0
stomatitis B-Disease 0
, O 0
anemia B-Disease 0
, O 0
and O 0
thrombocytopenia B-Disease 0
. O 0

Pneumonitis B-Disease 0
, O 0
probably O 0
or O 0
possibly O 0
related O 0
, O 0
mainly O 0
grade O 0
1 O 0
/ O 0
2 O 0
, O 0
occurred O 0
in O 0
25 O 0
% O 0
. O 0

Cox O 0
regression O 0
analysis O 0
of O 0
IHC O 0
scores O 0
found O 0
that O 0
only O 0
phospho O 0
AKT O 0
( O 0
pAKT O 0
) O 0
was O 0
a O 0
significant O 0
independent O 0
predictor O 0
of O 0
worse O 0
PFS O 0
. O 0

CONCLUSIONS O 0
: O 0
RAD001 B-Chemical 0
10 O 0
mg O 0
/ O 0
day O 0
was O 0
well O 0
tolerated O 0
, O 0
showing O 0
modest O 0
clinical O 0
activity O 0
in O 0
pretreated O 0
NSCLC B-Disease 0
. O 0

Evaluation O 0
of O 0
RAD001 B-Chemical 0
plus O 0
standard O 0
therapy O 0
for O 0
metastatic O 0
NSCLC B-Disease 0
continues O 0
. O 0

Posttransplant O 0
anemia B-Disease 0
: O 0
the O 0
role O 0
of O 0
sirolimus B-Chemical 0
. O 0

Posttransplant O 0
anemia B-Disease 0
is O 0
a O 0
common O 0
problem O 0
that O 0
may O 0
hinder O 0
patients O 0
' O 0
quality O 0
of O 0
life O 0
. O 0

It O 0
occurs O 0
in O 0
12 O 0
to O 0
76 O 0
% O 0
of O 0
patients O 0
, O 0
and O 0
is O 0
most O 0
common O 0
in O 0
the O 0
immediate O 0
posttransplant O 0
period O 0
. O 0

A O 0
variety O 0
of O 0
factors O 0
have O 0
been O 0
identified O 0
that O 0
increase O 0
the O 0
risk O 0
of O 0
posttransplant O 0
anemia B-Disease 0
, O 0
of O 0
which O 0
the O 0
level O 0
of O 0
renal O 0
function O 0
is O 0
most O 0
important O 0
. O 0

Sirolimus B-Chemical 0
, O 0
a O 0
mammalian O 0
target O 0
of O 0
rapamycin B-Chemical 0
inhibitor O 0
, O 0
has O 0
been O 0
implicated O 0
as O 0
playing O 0
a O 0
special O 0
role O 0
in O 0
posttransplant O 0
anemia B-Disease 0
. O 0

This O 0
review O 0
considers O 0
anemia B-Disease 0
associated O 0
with O 0
sirolimus B-Chemical 0
, O 0
including O 0
its O 0
presentation O 0
, O 0
mechanisms O 0
, O 0
and O 0
management O 0
. O 0

Coronary O 0
computerized O 0
tomography O 0
angiography O 0
for O 0
rapid O 0
discharge O 0
of O 0
low O 0
- O 0
risk O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Most O 0
patients O 0
presenting O 0
to O 0
emergency O 0
departments O 0
( O 0
EDs O 0
) O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
are O 0
admitted O 0
for O 0
at O 0
least O 0
12 O 0
hours O 0
and O 0
receive O 0
a O 0
" O 0
rule O 0
out O 0
acute B-Disease 0
coronary I-Disease 0
syndrome I-Disease 0
" O 0
protocol O 0
, O 0
often O 0
with O 0
noninvasive O 0
testing O 0
prior O 0
to O 0
discharge O 0
. O 0

In O 0
patients O 0
without O 0
cocaine B-Chemical 0
use O 0
, O 0
coronary O 0
computerized O 0
tomography O 0
angiography O 0
( O 0
CTA O 0
) O 0
has O 0
been O 0
shown O 0
to O 0
be O 0
useful O 0
for O 0
identifying O 0
a O 0
group O 0
of O 0
patients O 0
at O 0
low O 0
risk O 0
for O 0
cardiac O 0
events O 0
who O 0
can O 0
be O 0
safely O 0
discharged O 0
. O 0

It O 0
is O 0
unclear O 0
whether O 0
a O 0
coronary O 0
CTA O 0
strategy O 0
would O 0
be O 0
efficacious O 0
in O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
, O 0
as O 0
coronary B-Disease 0
vasospasm I-Disease 0
may O 0
account O 0
for O 0
some O 0
of O 0
the O 0
ischemia B-Disease 0
. O 0

We O 0
studied O 0
whether O 0
a O 0
negative O 0
coronary O 0
CTA O 0
in O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
could O 0
identify O 0
a O 0
subset O 0
safe O 0
for O 0
discharge O 0
. O 0

METHODS O 0
: O 0
We O 0
prospectively O 0
evaluated O 0
the O 0
safety O 0
of O 0
coronary O 0
CTA O 0
for O 0
low O 0
- O 0
risk O 0
patients O 0
who O 0
presented O 0
to O 0
the O 0
ED O 0
with O 0
cocaineassociated O 0
chest B-Disease 0
pain I-Disease 0
( O 0
self O 0
- O 0
reported O 0
or O 0
positive O 0
urine O 0
test O 0
) O 0
. O 0

Consecutive O 0
patients O 0
received O 0
either O 0
immediate O 0
coronary O 0
CTA O 0
in O 0
the O 0
ED O 0
( O 0
without O 0
serial O 0
markers O 0
) O 0
or O 0
underwent O 0
coronary O 0
CTA O 0
after O 0
a O 0
brief O 0
observation O 0
period O 0
with O 0
serial O 0
cardiac O 0
marker O 0
measurements O 0
. O 0

Patients O 0
with O 0
negative O 0
coronary O 0
CTA O 0
( O 0
maximal O 0
stenosis B-Disease 0
less O 0
than O 0
50 O 0
% O 0
) O 0
were O 0
discharged O 0
. O 0

The O 0
main O 0
outcome O 0
was O 0
30 O 0
- O 0
day O 0
cardiovascular O 0
death O 0
or O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

RESULTS O 0
: O 0
A O 0
total O 0
of O 0
59 O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
chest B-Disease 0
pain I-Disease 0
were O 0
evaluated O 0
. O 0

Patients O 0
had O 0
a O 0
mean O 0
age O 0
of O 0
45 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
6 O 0
. O 0
6 O 0
yrs O 0
and O 0
were O 0
86 O 0
% O 0
black O 0
, O 0
66 O 0
% O 0
male O 0
. O 0

Seventy O 0
- O 0
nine O 0
percent O 0
had O 0
a O 0
normal O 0
or O 0
nonspecific O 0
ECG O 0
and O 0
85 O 0
% O 0
had O 0
a O 0
TIMI O 0
score O 0
< O 0
2 O 0
. O 0

Twenty O 0
patients O 0
received O 0
coronary O 0
CTA O 0
immediately O 0
in O 0
the O 0
ED O 0
, O 0
18 O 0
of O 0
whom O 0
were O 0
discharged O 0
following O 0
CTA O 0
( O 0
90 O 0
% O 0
) O 0
. O 0

Thirty O 0
- O 0
nine O 0
received O 0
coronary O 0
CTA O 0
after O 0
a O 0
brief O 0
observation O 0
period O 0
, O 0
with O 0
37 O 0
discharged O 0
home O 0
following O 0
CTA O 0
( O 0
95 O 0
% O 0
) O 0
. O 0

Six O 0
patients O 0
had O 0
coronary B-Disease 0
stenosis I-Disease 0
> O 0
or O 0
= O 0
50 O 0
% O 0
. O 0

During O 0
the O 0
30 O 0
- O 0
day O 0
follow O 0
- O 0
up O 0
period O 0
, O 0
no O 0
patients O 0
died O 0
of O 0
a O 0
cardiovascular O 0
event O 0
( O 0
0 O 0
% O 0
; O 0
95 O 0
% O 0
CI O 0
, O 0
0 O 0
- O 0
6 O 0
. O 0
1 O 0
% O 0
) O 0
and O 0
no O 0
patient O 0
sustained O 0
a O 0
nonfatal O 0
myocardial B-Disease 0
infarction I-Disease 0
( O 0
0 O 0
% O 0
; O 0
95 O 0
% O 0
CI O 0
, O 0
0 O 0
- O 0
6 O 0
. O 0
1 O 0
% O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Although O 0
cocaine B-Chemical 0
- O 0
associated O 0
myocardial B-Disease 0
ischemia I-Disease 0
can O 0
result O 0
from O 0
coronary O 0
vasoconstriction O 0
, O 0
patients O 0
with O 0
cocaine B-Chemical 0
associated O 0
chest B-Disease 0
pain I-Disease 0
, O 0
a O 0
non O 0
- O 0
ischemic B-Disease 0
ECG O 0
, O 0
and O 0
a O 0
TIMI O 0
risk O 0
score O 0
< O 0
2 O 0
may O 0
be O 0
safely O 0
discharged O 0
from O 0
the O 0
ED O 0
after O 0
a O 0
negative O 0
coronary O 0
CTA O 0
with O 0
a O 0
low O 0
risk O 0
of O 0
30 O 0
- O 0
day O 0
adverse O 0
events O 0
. O 0

Bilateral O 0
haemorrhagic B-Disease 0
infarction I-Disease 0
of I-Disease 0
the I-Disease 0
globus I-Disease 0
pallidus I-Disease 0
after O 0
cocaine B-Chemical 0
and O 0
alcohol B-Chemical 0
intoxication O 0
. O 0

Cocaine B-Chemical 0
is O 0
a O 0
risk O 0
factor O 0
for O 0
both O 0
ischemic B-Disease 0
and I-Disease 0
haemorrhagic I-Disease 0
stroke I-Disease 0
. O 0

We O 0
present O 0
the O 0
case O 0
of O 0
a O 0
31 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
bilateral O 0
ischemia B-Disease 0
of I-Disease 0
the I-Disease 0
globus I-Disease 0
pallidus I-Disease 0
after O 0
excessive O 0
alcohol B-Chemical 0
and O 0
intranasal O 0
cocaine B-Chemical 0
use O 0
. O 0

Drug O 0
- O 0
related O 0
globus B-Disease 0
pallidus I-Disease 0
infarctions I-Disease 0
are O 0
most O 0
often O 0
associated O 0
with O 0
heroin B-Chemical 0
. O 0

Bilateral O 0
basal B-Disease 0
ganglia I-Disease 0
infarcts I-Disease 0
after O 0
the O 0
use O 0
of O 0
cocaine B-Chemical 0
, O 0
without O 0
concurrent O 0
heroin B-Chemical 0
use O 0
, O 0
have O 0
never O 0
been O 0
reported O 0
. O 0

In O 0
our O 0
patient O 0
, O 0
transient O 0
cardiac B-Disease 0
arrhythmia I-Disease 0
or O 0
respiratory B-Disease 0
dysfunction I-Disease 0
related O 0
to O 0
cocaine B-Chemical 0
and O 0
/ O 0
or O 0
ethanol B-Chemical 0
use O 0
were O 0
the O 0
most O 0
likely O 0
causes O 0
of O 0
cerebral B-Disease 0
hypoperfusion I-Disease 0
. O 0

Late O 0
fulminant O 0
posterior B-Disease 0
reversible I-Disease 0
encephalopathy I-Disease 0
syndrome I-Disease 0
after O 0
liver O 0
transplant O 0
. O 0

OBJECTIVES O 0
: O 0
Posterior B-Disease 0
leukoencephalopathy I-Disease 0
due O 0
to O 0
calcineurin O 0
- O 0
inhibitor O 0
- O 0
related O 0
neurotoxicity B-Disease 0
is O 0
a O 0
rare O 0
but O 0
severe O 0
complication O 0
that O 0
results O 0
from O 0
treatment O 0
with O 0
immunosuppressive O 0
agents O 0
( O 0
primarily O 0
those O 0
administered O 0
after O 0
a O 0
liver O 0
or O 0
kidney O 0
transplant O 0
) O 0
. O 0

The O 0
pathophysiologic O 0
mechanisms O 0
of O 0
that O 0
disorder O 0
remain O 0
unknown O 0
. O 0

CASE O 0
: O 0
We O 0
report O 0
the O 0
case O 0
of O 0
a O 0
46 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
who O 0
received O 0
a O 0
liver O 0
transplant O 0
in O 0
our O 0
center O 0
as O 0
treatment O 0
for O 0
alcoholic B-Disease 0
cirrhosis I-Disease 0
and O 0
in O 0
whom O 0
either O 0
a O 0
fulminant O 0
course O 0
of O 0
posterior B-Disease 0
leukoencephalopathy I-Disease 0
or O 0
posterior B-Disease 0
reversible I-Disease 0
encephalopathy I-Disease 0
syndrome I-Disease 0
developed O 0
110 O 0
days O 0
after O 0
transplant O 0
. O 0

After O 0
an O 0
initially O 0
uneventful O 0
course O 0
after O 0
the O 0
transplant O 0
, O 0
the O 0
patient O 0
rapidly O 0
fell O 0
into O 0
deep O 0
coma O 0
. O 0

RESULTS O 0
: O 0
Cerebral O 0
MRI O 0
scan O 0
showed O 0
typical O 0
signs O 0
of O 0
enhancement O 0
in O 0
the O 0
pontine O 0
and O 0
posterior O 0
regions O 0
. O 0

Switching O 0
the O 0
immunosuppressive O 0
regimen O 0
from O 0
tacrolimus B-Chemical 0
to O 0
cyclosporine B-Chemical 0
did O 0
not O 0
improve O 0
the O 0
clinical O 0
situation O 0
. O 0

The O 0
termination O 0
of O 0
treatment O 0
with O 0
any O 0
calcineurin O 0
inhibitor O 0
resulted O 0
in O 0
a O 0
complete O 0
resolution O 0
of O 0
that O 0
complication O 0
. O 0

CONCLUSIONS O 0
: O 0
Posterior B-Disease 0
reversible I-Disease 0
encephalopathy I-Disease 0
syndrome I-Disease 0
after O 0
liver O 0
transplant O 0
is O 0
rare O 0
. O 0

We O 0
recommend O 0
a O 0
complete O 0
cessation O 0
of O 0
any O 0
calcineurin O 0
inhibitor O 0
rather O 0
than O 0
a O 0
dose O 0
reduction O 0
. O 0

Prolonged O 0
hypothermia B-Disease 0
as O 0
a O 0
bridge O 0
to O 0
recovery O 0
for O 0
cerebral B-Disease 0
edema I-Disease 0
and O 0
intracranial B-Disease 0
hypertension I-Disease 0
associated O 0
with O 0
fulminant B-Disease 0
hepatic I-Disease 0
failure I-Disease 0
. O 0

BACKGROUND O 0
: O 0
To O 0
review O 0
evidence O 0
- O 0
based O 0
treatment O 0
options O 0
in O 0
patients O 0
with O 0
cerebral B-Disease 0
edema I-Disease 0
complicating O 0
fulminant B-Disease 0
hepatic I-Disease 0
failure I-Disease 0
( O 0
FHF B-Disease 0
) O 0
and O 0
discuss O 0
the O 0
potential O 0
applications O 0
of O 0
hypothermia B-Disease 0
. O 0

METHOD O 0
: O 0
Case O 0
- O 0
based O 0
observations O 0
from O 0
a O 0
medical O 0
intensive O 0
care O 0
unit O 0
( O 0
MICU O 0
) O 0
in O 0
a O 0
tertiary O 0
care O 0
facility O 0
in O 0
a O 0
27 O 0
- O 0
year O 0
- O 0
old O 0
female O 0
with O 0
FHF B-Disease 0
from O 0
acetaminophen B-Chemical 0
and O 0
resultant O 0
cerebral B-Disease 0
edema I-Disease 0
. O 0

RESULTS O 0
: O 0
Our O 0
patient O 0
was O 0
admitted O 0
to O 0
the O 0
MICU O 0
after O 0
being O 0
found O 0
unresponsive O 0
with O 0
presumed O 0
toxicity B-Disease 0
from O 0
acetaminophen B-Chemical 0
which O 0
was O 0
ingested O 0
over O 0
a O 0
2 O 0
- O 0
day O 0
period O 0
. O 0

The O 0
patient O 0
had O 0
depressed O 0
of O 0
mental O 0
status O 0
lasting O 0
at O 0
least O 0
24 O 0
h O 0
prior O 0
to O 0
admission O 0
. O 0

Initial O 0
evaluation O 0
confirmed O 0
FHF B-Disease 0
from O 0
acetaminophen B-Chemical 0
and O 0
cerebral B-Disease 0
edema I-Disease 0
. O 0

The O 0
patient O 0
was O 0
treated O 0
with O 0
hyperosmolar O 0
therapy O 0
, O 0
hyperventilation B-Disease 0
, O 0
sedation O 0
, O 0
and O 0
chemical O 0
paralysis B-Disease 0
. O 0

Her O 0
intracranial O 0
pressure O 0
remained O 0
elevated O 0
despite O 0
maximal O 0
medical O 0
therapy O 0
. O 0

We O 0
then O 0
initiated O 0
therapeutic O 0
hypothermia B-Disease 0
which O 0
was O 0
continued O 0
for O 0
5 O 0
days O 0
. O 0

At O 0
re O 0
- O 0
warming O 0
, O 0
patient O 0
had O 0
resolution O 0
of O 0
her O 0
cerebral B-Disease 0
edema I-Disease 0
and O 0
intracranial B-Disease 0
hypertension I-Disease 0
. O 0

At O 0
discharge O 0
, O 0
she O 0
had O 0
complete O 0
recovery O 0
of O 0
neurological O 0
and O 0
hepatic O 0
functions O 0
. O 0

CONCLUSION O 0
: O 0
In O 0
patients O 0
with O 0
FHF B-Disease 0
and O 0
cerebral B-Disease 0
edema I-Disease 0
from O 0
acetaminophen B-Chemical 0
overdose B-Disease 0
, O 0
prolonged O 0
therapeutic O 0
hypothermia B-Disease 0
could O 0
potentially O 0
be O 0
used O 0
as O 0
a O 0
life O 0
saving O 0
therapy O 0
and O 0
a O 0
bridge O 0
to O 0
hepatic O 0
and O 0
neurological O 0
recovery O 0
. O 0

A O 0
clinical O 0
trial O 0
of O 0
hypothermia B-Disease 0
in O 0
patients O 0
with O 0
this O 0
condition O 0
is O 0
warranted O 0
. O 0

Binasal B-Disease 0
visual I-Disease 0
field I-Disease 0
defects I-Disease 0
are O 0
not O 0
specific O 0
to O 0
vigabatrin B-Chemical 0
. O 0

This O 0
study O 0
investigated O 0
the O 0
visual B-Disease 0
defects I-Disease 0
associated O 0
with O 0
the O 0
antiepileptic O 0
drug O 0
vigabatrin B-Chemical 0
( O 0
VGB B-Chemical 0
) O 0
. O 0

Two O 0
hundred O 0
four O 0
people O 0
with O 0
epilepsy B-Disease 0
were O 0
grouped O 0
on O 0
the O 0
basis O 0
of O 0
antiepileptic O 0
drug O 0
therapy O 0
( O 0
current O 0
, O 0
previous O 0
, O 0
or O 0
no O 0
exposure O 0
to O 0
VGB B-Chemical 0
) O 0
. O 0

Groups O 0
were O 0
matched O 0
with O 0
respect O 0
to O 0
age O 0
, O 0
gender O 0
, O 0
and O 0
seizure B-Disease 0
frequency O 0
. O 0

All O 0
patients O 0
underwent O 0
objective O 0
assessment O 0
of O 0
electrophysiological O 0
function O 0
( O 0
wide O 0
- O 0
field O 0
multifocal O 0
electroretinography O 0
) O 0
and O 0
conventional O 0
visual O 0
field O 0
testing O 0
( O 0
static O 0
perimetry O 0
) O 0
. O 0

Bilateral O 0
visual O 0
field O 0
constriction O 0
was O 0
observed O 0
in O 0
59 O 0
% O 0
of O 0
patients O 0
currently O 0
taking O 0
VGB B-Chemical 0
, O 0
43 O 0
% O 0
of O 0
patients O 0
who O 0
previously O 0
took O 0
VGB B-Chemical 0
, O 0
and O 0
24 O 0
% O 0
of O 0
patients O 0
with O 0
no O 0
exposure O 0
to O 0
VGB B-Chemical 0
. O 0

Assessment O 0
of O 0
retinal O 0
function O 0
revealed O 0
abnormal O 0
responses O 0
in O 0
48 O 0
% O 0
of O 0
current O 0
VGB B-Chemical 0
users O 0
and O 0
22 O 0
% O 0
of O 0
prior O 0
VGB B-Chemical 0
users O 0
, O 0
but O 0
in O 0
none O 0
of O 0
the O 0
patients O 0
without O 0
previous O 0
exposure O 0
to O 0
VGB B-Chemical 0
. O 0

Bilateral B-Disease 0
visual I-Disease 0
field I-Disease 0
abnormalities I-Disease 0
are O 0
common O 0
in O 0
the O 0
treated O 0
epilepsy B-Disease 0
population O 0
, O 0
irrespective O 0
of O 0
drug O 0
history O 0
. O 0

Assessment O 0
by O 0
conventional O 0
static O 0
perimetry O 0
may O 0
neither O 0
be O 0
sufficiently O 0
sensitive O 0
nor O 0
specific O 0
to O 0
reliably O 0
identify O 0
retinal B-Disease 0
toxicity I-Disease 0
associated O 0
with O 0
VGB B-Chemical 0
. O 0

Smoking O 0
of O 0
crack B-Chemical 0
cocaine I-Chemical 0
as O 0
a O 0
risk O 0
factor O 0
for O 0
HIV B-Disease 0
infection I-Disease 0
among O 0
people O 0
who O 0
use O 0
injection O 0
drugs O 0
. O 0

BACKGROUND O 0
: O 0
Little O 0
is O 0
known O 0
about O 0
the O 0
possible O 0
role O 0
that O 0
smoking O 0
crack B-Chemical 0
cocaine I-Chemical 0
has O 0
on O 0
the O 0
incidence O 0
of O 0
HIV B-Disease 0
infection I-Disease 0
. O 0

Given O 0
the O 0
increasing O 0
use O 0
of O 0
crack B-Chemical 0
cocaine I-Chemical 0
, O 0
we O 0
sought O 0
to O 0
examine O 0
whether O 0
use O 0
of O 0
this O 0
illicit O 0
drug O 0
has O 0
become O 0
a O 0
risk O 0
factor O 0
for O 0
HIV B-Disease 0
infection I-Disease 0
. O 0

METHODS O 0
: O 0
We O 0
included O 0
data O 0
from O 0
people O 0
participating O 0
in O 0
the O 0
Vancouver O 0
Injection O 0
Drug O 0
Users O 0
Study O 0
who O 0
reported O 0
injecting O 0
illicit O 0
drugs O 0
at O 0
least O 0
once O 0
in O 0
the O 0
month O 0
before O 0
enrolment O 0
, O 0
lived O 0
in O 0
the O 0
greater O 0
Vancouver O 0
area O 0
, O 0
were O 0
HIV O 0
- O 0
negative O 0
at O 0
enrolment O 0
and O 0
completed O 0
at O 0
least O 0
1 O 0
follow O 0
- O 0
up O 0
study O 0
visit O 0
. O 0

To O 0
determine O 0
whether O 0
the O 0
risk O 0
of O 0
HIV B-Disease 0
seroconversion I-Disease 0
among O 0
daily O 0
smokers O 0
of O 0
crack B-Chemical 0
cocaine I-Chemical 0
changed O 0
over O 0
time O 0
, O 0
we O 0
used O 0
Cox O 0
proportional O 0
hazards O 0
regression O 0
and O 0
divided O 0
the O 0
study O 0
into O 0
3 O 0
periods O 0
: O 0
May O 0
1 O 0
, O 0
1996 O 0
- O 0
Nov O 0
. O 0

30 O 0
, O 0
1999 O 0
( O 0
period O 0
1 O 0
) O 0
, O 0
Dec O 0
. O 0

1 O 0
, O 0
1999 O 0
- O 0
Nov O 0
. O 0

30 O 0
, O 0
2002 O 0
( O 0
period O 0
2 O 0
) O 0
, O 0
and O 0
Dec O 0
. O 0

1 O 0
, O 0
2002 O 0
- O 0
Dec O 0
. O 0

30 O 0
, O 0
2005 O 0
( O 0
period O 0
3 O 0
) O 0
. O 0

RESULTS O 0
: O 0
Overall O 0
, O 0
1048 O 0
eligible O 0
injection O 0
drug O 0
users O 0
were O 0
included O 0
in O 0
our O 0
study O 0
. O 0

Of O 0
these O 0
, O 0
137 O 0
acquired O 0
HIV B-Disease 0
infection I-Disease 0
during O 0
follow O 0
- O 0
up O 0
. O 0

The O 0
mean O 0
proportion O 0
of O 0
participants O 0
who O 0
reported O 0
daily O 0
smoking O 0
of O 0
crack B-Chemical 0
cocaine I-Chemical 0
increased O 0
from O 0
11 O 0
. O 0
6 O 0
% O 0
in O 0
period O 0
1 O 0
to O 0
39 O 0
. O 0
7 O 0
% O 0
in O 0
period O 0
3 O 0
. O 0

After O 0
adjusting O 0
for O 0
potential O 0
confounders O 0
, O 0
we O 0
found O 0
that O 0
the O 0
risk O 0
of O 0
HIV B-Disease 0
seroconversion I-Disease 0
among O 0
participants O 0
who O 0
were O 0
daily O 0
smokers O 0
of O 0
crack B-Chemical 0
cocaine I-Chemical 0
increased O 0
over O 0
time O 0
( O 0
period O 0
1 O 0
: O 0
hazard O 0
ratio O 0
[ O 0
HR O 0
] O 0
1 O 0
. O 0
03 O 0
, O 0
95 O 0
% O 0
confidence O 0
interval O 0
[ O 0
CI O 0
] O 0
0 O 0
. O 0
57 O 0
- O 0
1 O 0
. O 0
85 O 0
; O 0
period O 0
2 O 0
: O 0
HR O 0
1 O 0
. O 0
68 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
01 O 0
- O 0
2 O 0
. O 0
80 O 0
; O 0
and O 0
period O 0
3 O 0
: O 0
HR O 0
2 O 0
. O 0
74 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
06 O 0
- O 0
7 O 0
. O 0
11 O 0
) O 0
. O 0

INTERPRETATION O 0
: O 0
Smoking O 0
of O 0
crack B-Chemical 0
cocaine I-Chemical 0
was O 0
found O 0
to O 0
be O 0
an O 0
independent O 0
risk O 0
factor O 0
for O 0
HIV B-Disease 0
seroconversion I-Disease 0
among O 0
people O 0
who O 0
were O 0
injection O 0
drug O 0
users O 0
. O 0

This O 0
finding O 0
points O 0
to O 0
the O 0
urgent O 0
need O 0
for O 0
evidence O 0
- O 0
based O 0
public O 0
health O 0
initiatives O 0
targeted O 0
at O 0
people O 0
who O 0
smoke O 0
crack B-Chemical 0
cocaine I-Chemical 0
. O 0

Fluoxetine B-Chemical 0
improves O 0
the O 0
memory B-Disease 0
deficits I-Disease 0
caused O 0
by O 0
the O 0
chemotherapy O 0
agent O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
. O 0

Cancer B-Disease 0
patients O 0
who O 0
have O 0
been O 0
treated O 0
with O 0
systemic O 0
adjuvant O 0
chemotherapy O 0
have O 0
described O 0
experiencing O 0
deteriorations O 0
in O 0
cognition O 0
. O 0

A O 0
widely O 0
used O 0
chemotherapeutic O 0
agent O 0
, O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
( O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
) O 0
, O 0
readily O 0
crosses O 0
the O 0
blood O 0
- O 0
brain O 0
barrier O 0
and O 0
so O 0
could O 0
have O 0
a O 0
direct O 0
effect O 0
on O 0
brain O 0
function O 0
. O 0

In O 0
particular O 0
this O 0
anti O 0
mitotic O 0
drug O 0
could O 0
reduce O 0
cell O 0
proliferation O 0
in O 0
the O 0
neurogenic O 0
regions O 0
of O 0
the O 0
adult O 0
brain O 0
. O 0

In O 0
contrast O 0
reports O 0
indicate O 0
that O 0
hippocampal O 0
dependent O 0
neurogenesis O 0
and O 0
cognition O 0
are O 0
enhanced O 0
by O 0
the O 0
SSRI B-Chemical 0
antidepressant O 0
Fluoxetine B-Chemical 0
. O 0

In O 0
this O 0
investigation O 0
the O 0
behavioural O 0
effects O 0
of O 0
chronic O 0
( O 0
two O 0
week O 0
) O 0
treatment O 0
with O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
and O 0
( O 0
three O 0
weeks O 0
) O 0
with O 0
Fluoxetine B-Chemical 0
either O 0
separately O 0
or O 0
in O 0
combination O 0
with O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
were O 0
tested O 0
on O 0
adult O 0
Lister O 0
hooded O 0
rats O 0
. O 0

Behavioural O 0
effects O 0
were O 0
tested O 0
using O 0
a O 0
context O 0
dependent O 0
conditioned O 0
emotional O 0
response O 0
test O 0
( O 0
CER O 0
) O 0
which O 0
showed O 0
that O 0
animals O 0
treated O 0
with O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
had O 0
a O 0
significant O 0
reduction O 0
in O 0
freezing O 0
time O 0
compared O 0
to O 0
controls O 0
. O 0

A O 0
separate O 0
group O 0
of O 0
animals O 0
was O 0
tested O 0
using O 0
a O 0
hippocampal O 0
dependent O 0
spatial O 0
working O 0
memory O 0
test O 0
, O 0
the O 0
object O 0
location O 0
recognition O 0
test O 0
( O 0
OLR O 0
) O 0
. O 0

Animals O 0
treated O 0
only O 0
with O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
showed O 0
significant O 0
deficits O 0
in O 0
their O 0
ability O 0
to O 0
carry O 0
out O 0
the O 0
OLR O 0
task O 0
but O 0
co O 0
administration O 0
of O 0
Fluoxetine B-Chemical 0
improved O 0
their O 0
performance O 0
. O 0

5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
chemotherapy O 0
caused O 0
a O 0
significant O 0
reduction O 0
in O 0
the O 0
number O 0
of O 0
proliferating O 0
cells O 0
in O 0
the O 0
sub O 0
granular O 0
zone O 0
of O 0
the O 0
dentate O 0
gyrus O 0
compared O 0
to O 0
controls O 0
. O 0

This O 0
reduction O 0
was O 0
eliminated O 0
when O 0
Fluoxetine B-Chemical 0
was O 0
co O 0
administered O 0
with O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
. O 0

Fluoxetine B-Chemical 0
on O 0
its O 0
own O 0
had O 0
no O 0
effect O 0
on O 0
proliferating O 0
cell O 0
number O 0
or O 0
behaviour O 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
can O 0
negatively O 0
affect O 0
both O 0
cell O 0
proliferation O 0
and O 0
hippocampal O 0
dependent O 0
working O 0
memory O 0
and O 0
that O 0
these O 0
deficits O 0
can O 0
be O 0
reversed O 0
by O 0
the O 0
simultaneous O 0
administration O 0
of O 0
the O 0
antidepressant O 0
Fluoxetine B-Chemical 0
. O 0

Liver O 0
- O 0
specific O 0
ablation O 0
of O 0
integrin O 0
- O 0
linked O 0
kinase O 0
in O 0
mice O 0
results O 0
in O 0
enhanced O 0
and O 0
prolonged O 0
cell O 0
proliferation O 0
and O 0
hepatomegaly B-Disease 0
after O 0
phenobarbital B-Chemical 0
administration O 0
. O 0

We O 0
have O 0
recently O 0
demonstrated O 0
that O 0
disruption O 0
of O 0
extracellular O 0
matrix O 0
( O 0
ECM O 0
) O 0
/ O 0
integrin O 0
signaling O 0
via O 0
elimination O 0
of O 0
integrin O 0
- O 0
linked O 0
kinase O 0
( O 0
ILK O 0
) O 0
in O 0
hepatocytes O 0
interferes O 0
with O 0
signals O 0
leading O 0
to O 0
termination O 0
of O 0
liver O 0
regeneration O 0
. O 0

This O 0
study O 0
investigates O 0
the O 0
role O 0
of O 0
ILK O 0
in O 0
liver O 0
enlargement O 0
induced O 0
by O 0
phenobarbital B-Chemical 0
( O 0
PB B-Chemical 0
) O 0
. O 0

Wild O 0
- O 0
type O 0
( O 0
WT O 0
) O 0
and O 0
ILK O 0
: O 0
liver O 0
- O 0
/ O 0
- O 0
mice O 0
were O 0
given O 0
PB B-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
% O 0
in O 0
drinking O 0
water O 0
) O 0
for O 0
10 O 0
days O 0
. O 0

Livers O 0
were O 0
harvested O 0
on O 0
2 O 0
, O 0
5 O 0
, O 0
and O 0
10 O 0
days O 0
during O 0
PB B-Chemical 0
administration O 0
. O 0

In O 0
the O 0
hepatocyte O 0
- O 0
specific O 0
ILK O 0
/ O 0
liver O 0
- O 0
/ O 0
- O 0
mice O 0
, O 0
the O 0
liver O 0
: O 0
body O 0
weight O 0
ratio O 0
was O 0
more O 0
than O 0
double O 0
as O 0
compared O 0
to O 0
0 O 0
h O 0
at O 0
day O 0
2 O 0
( O 0
2 O 0
. O 0
5 O 0
times O 0
) O 0
, O 0
while O 0
at O 0
days O 0
5 O 0
and O 0
10 O 0
, O 0
it O 0
was O 0
enlarged O 0
three O 0
times O 0
. O 0

In O 0
the O 0
WT O 0
mice O 0
, O 0
the O 0
increase O 0
was O 0
as O 0
expected O 0
from O 0
previous O 0
literature O 0
( O 0
1 O 0
. O 0
8 O 0
times O 0
) O 0
and O 0
seems O 0
to O 0
have O 0
leveled O 0
off O 0
after O 0
day O 0
2 O 0
. O 0

There O 0
were O 0
slightly O 0
increased O 0
proliferating O 0
cell O 0
nuclear O 0
antigen O 0
- O 0
positive O 0
cells O 0
in O 0
the O 0
ILK O 0
/ O 0
liver O 0
- O 0
/ O 0
- O 0
animals O 0
at O 0
day O 0
2 O 0
as O 0
compared O 0
to O 0
WT O 0
after O 0
PB B-Chemical 0
administration O 0
. O 0

In O 0
the O 0
WT O 0
animals O 0
, O 0
the O 0
proliferative O 0
response O 0
had O 0
come O 0
back O 0
to O 0
normal O 0
by O 0
days O 0
5 O 0
and O 0
10 O 0
. O 0

Hepatocytes O 0
of O 0
the O 0
ILK O 0
/ O 0
liver O 0
- O 0
/ O 0
- O 0
mice O 0
continued O 0
to O 0
proliferate O 0
up O 0
until O 0
day O 0
10 O 0
. O 0

ILK O 0
/ O 0
liver O 0
- O 0
/ O 0
- O 0
mice O 0
also O 0
showed O 0
increased O 0
expression O 0
of O 0
key O 0
genes O 0
involved O 0
in O 0
hepatocyte O 0
proliferation O 0
at O 0
different O 0
time O 0
points O 0
during O 0
PB B-Chemical 0
administration O 0
. O 0

In O 0
summary O 0
, O 0
ECM O 0
proteins O 0
communicate O 0
with O 0
the O 0
signaling O 0
machinery O 0
of O 0
dividing O 0
cells O 0
via O 0
ILK O 0
to O 0
regulate O 0
hepatocyte O 0
proliferation O 0
and O 0
termination O 0
of O 0
the O 0
proliferative O 0
response O 0
. O 0

Lack O 0
of O 0
ILK O 0
in O 0
the O 0
hepatocytes O 0
imparts O 0
prolonged O 0
proliferative O 0
response O 0
not O 0
only O 0
to O 0
stimuli O 0
related O 0
to O 0
liver O 0
regeneration O 0
but O 0
also O 0
to O 0
xenobiotic O 0
chemical O 0
mitogens O 0
, O 0
such O 0
as O 0
PB B-Chemical 0
. O 0

Decreased O 0
Expression O 0
of O 0
Na B-Chemical 0
/ O 0
K B-Chemical 0
- O 0
ATPase O 0
, O 0
NHE3 O 0
, O 0
NBC1 O 0
, O 0
AQP1 O 0
and O 0
OAT O 0
in O 0
Gentamicin B-Chemical 0
- O 0
induced O 0
Nephropathy B-Disease 0
. O 0

The O 0
present O 0
study O 0
was O 0
aimed O 0
to O 0
determine O 0
whether O 0
there O 0
is O 0
an O 0
altered O 0
regulation O 0
of O 0
tubular O 0
transporters O 0
in O 0
gentamicin B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
. O 0

Sprague O 0
- O 0
Dawley O 0
male O 0
rats O 0
( O 0
200 O 0
~ O 0
250 O 0
g O 0
) O 0
were O 0
subcutaneously O 0
injected O 0
with O 0
gentamicin B-Chemical 0
( O 0
100 O 0
mg O 0
/ O 0
kg O 0
per O 0
day O 0
) O 0
for O 0
7 O 0
days O 0
, O 0
and O 0
the O 0
expression O 0
of O 0
tubular O 0
transporters O 0
was O 0
determined O 0
by O 0
immunoblotting O 0
and O 0
immunohistochemistry O 0
. O 0

The O 0
mRNA O 0
and O 0
protein O 0
expression O 0
of O 0
OAT O 0
was O 0
also O 0
determined O 0
. O 0

Gentamicin B-Chemical 0
- O 0
treated O 0
rats O 0
exhibited O 0
significantly O 0
decreased O 0
creatinine B-Chemical 0
clearance O 0
along O 0
with O 0
increased O 0
plasma O 0
creatinine B-Chemical 0
levels O 0
. O 0

Accordingly O 0
, O 0
the O 0
fractional O 0
excretion O 0
of O 0
sodium B-Chemical 0
increased O 0
. O 0

Urine O 0
volume O 0
was O 0
increased O 0
, O 0
while O 0
urine O 0
osmolality O 0
and O 0
free O 0
water O 0
reabsorption O 0
were O 0
decreased O 0
. O 0

Immunoblotting O 0
and O 0
immunohistochemistry O 0
revealed O 0
decreased O 0
expression O 0
of O 0
Na B-Chemical 0
( O 0
+ O 0
) O 0
/ O 0
K B-Chemical 0
( O 0
+ O 0
) O 0
- O 0
ATPase O 0
, O 0
NHE3 O 0
, O 0
NBC1 O 0
, O 0
and O 0
AQP1 O 0
in O 0
the O 0
kidney O 0
of O 0
gentamicin B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

The O 0
expression O 0
of O 0
OAT1 O 0
and O 0
OAT3 O 0
was O 0
also O 0
decreased O 0
. O 0

Gentamicin B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
may O 0
at O 0
least O 0
in O 0
part O 0
be O 0
causally O 0
related O 0
with O 0
a O 0
decreased O 0
expression O 0
of O 0
Na B-Chemical 0
( O 0
+ O 0
) O 0
/ O 0
K B-Chemical 0
( O 0
+ O 0
) O 0
- O 0
ATPase O 0
, O 0
NHE3 O 0
, O 0
NBC1 O 0
, O 0
AQP1 O 0
and O 0
OAT O 0
. O 0

Acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
after O 0
high O 0
- O 0
dose O 0
methotrexate B-Chemical 0
therapy O 0
in O 0
a O 0
patient O 0
with O 0
ileostomy O 0
. O 0

High O 0
- O 0
dose O 0
methotrexate B-Chemical 0
( O 0
HD O 0
- O 0
MTX B-Chemical 0
) O 0
is O 0
an O 0
important O 0
treatment O 0
for O 0
Burkitt B-Disease 0
lymphoma I-Disease 0
, O 0
but O 0
can O 0
cause O 0
hepatic B-Disease 0
and I-Disease 0
renal I-Disease 0
toxicity I-Disease 0
when O 0
its O 0
clearance O 0
is O 0
delayed O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
after O 0
HD O 0
- O 0
MTX B-Chemical 0
therapy O 0
in O 0
a O 0
patient O 0
with O 0
ileostomy O 0
, O 0
The O 0
patient O 0
was O 0
a O 0
3 O 0
- O 0
year O 0
- O 0
old O 0
boy O 0
who O 0
had O 0
received O 0
a O 0
living O 0
- O 0
related O 0
liver O 0
transplantation O 0
for O 0
congenital O 0
biliary B-Disease 0
atresia I-Disease 0
. O 0

At O 0
day O 0
833 O 0
after O 0
the O 0
transplantation O 0
, O 0
he O 0
was O 0
diagnosed O 0
with O 0
PTLD B-Disease 0
( O 0
post B-Disease 0
- I-Disease 0
transplantation I-Disease 0
lymphoproliferative I-Disease 0
disorder I-Disease 0
, O 0
Burkitt B-Disease 0
- I-Disease 0
type I-Disease 0
malignant I-Disease 0
lymphoma I-Disease 0
) O 0
. O 0

During O 0
induction O 0
therapy O 0
, O 0
he O 0
suffered O 0
ileal O 0
perforation O 0
and O 0
ileostomy O 0
was O 0
performed O 0
. O 0

Subsequent O 0
HD O 0
- O 0
MTX B-Chemical 0
therapy O 0
caused O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
that O 0
required O 0
continuous O 0
hemodialysis O 0
. O 0

We O 0
supposed O 0
that O 0
intravascular O 0
hypovolemia B-Disease 0
due O 0
to O 0
substantial O 0
drainage O 0
from O 0
the O 0
ileostoma O 0
caused O 0
acute B-Disease 0
prerenal I-Disease 0
failure I-Disease 0
. O 0

After O 0
recovery O 0
of O 0
his O 0
renal O 0
function O 0
, O 0
we O 0
could O 0
safely O 0
treat O 0
the O 0
patient O 0
with O 0
HD O 0
- O 0
MTX B-Chemical 0
therapy O 0
by O 0
controlling O 0
drainage O 0
from O 0
ileostoma O 0
with O 0
total O 0
parenteral O 0
nutrition O 0
. O 0

Longitudinal O 0
association O 0
of O 0
alcohol B-Chemical 0
use O 0
with O 0
HIV B-Disease 0
disease I-Disease 0
progression O 0
and O 0
psychological O 0
health O 0
of O 0
women O 0
with O 0
HIV O 0
. O 0

We O 0
evaluated O 0
the O 0
association O 0
of O 0
alcohol B-Chemical 0
consumption O 0
and O 0
depression B-Disease 0
, O 0
and O 0
their O 0
effects O 0
on O 0
HIV B-Disease 0
disease I-Disease 0
progression O 0
among O 0
women O 0
with O 0
HIV O 0
. O 0

The O 0
study O 0
included O 0
871 O 0
women O 0
with O 0
HIV O 0
who O 0
were O 0
recruited O 0
from O 0
1993 O 0
- O 0
1995 O 0
in O 0
four O 0
US O 0
cities O 0
. O 0

The O 0
participants O 0
had O 0
physical O 0
examination O 0
, O 0
medical O 0
record O 0
extraction O 0
, O 0
and O 0
venipuncture O 0
, O 0
CD4 O 0
+ O 0
T O 0
- O 0
cell O 0
counts O 0
determination O 0
, O 0
measurement O 0
of O 0
depression B-Disease 0
symptoms O 0
( O 0
using O 0
the O 0
self O 0
- O 0
report O 0
Center O 0
for O 0
Epidemiological O 0
Studies O 0
- O 0
Depression B-Disease 0
Scale O 0
) O 0
, O 0
and O 0
alcohol B-Chemical 0
use O 0
assessment O 0
at O 0
enrollment O 0
, O 0
and O 0
semiannually O 0
until O 0
March O 0
2000 O 0
. O 0

Multilevel O 0
random O 0
coefficient O 0
ordinal O 0
models O 0
as O 0
well O 0
as O 0
multilevel O 0
models O 0
with O 0
joint O 0
responses O 0
were O 0
used O 0
in O 0
the O 0
analysis O 0
. O 0

There O 0
was O 0
no O 0
significant O 0
association O 0
between O 0
level O 0
of O 0
alcohol B-Chemical 0
use O 0
and O 0
CD4 O 0
+ O 0
T O 0
- O 0
cell O 0
counts O 0
. O 0

When O 0
participants O 0
were O 0
stratified O 0
by O 0
antiretroviral O 0
therapy O 0
( O 0
ART O 0
) O 0
use O 0
, O 0
the O 0
association O 0
between O 0
alcohol B-Chemical 0
and O 0
CD4 O 0
+ O 0
T O 0
- O 0
cell O 0
did O 0
not O 0
reach O 0
statistical O 0
significance O 0
. O 0

The O 0
association O 0
between O 0
alcohol B-Chemical 0
consumption O 0
and O 0
depression B-Disease 0
was O 0
significant O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Depression B-Disease 0
had O 0
a O 0
significant O 0
negative O 0
effect O 0
on O 0
CD4 O 0
+ O 0
T O 0
- O 0
cell O 0
counts O 0
over O 0
time O 0
regardless O 0
of O 0
ART O 0
use O 0
. O 0

Our O 0
findings O 0
suggest O 0
that O 0
alcohol B-Chemical 0
consumption O 0
has O 0
a O 0
direct O 0
association O 0
with O 0
depression B-Disease 0
. O 0

Moreover O 0
, O 0
depression B-Disease 0
is O 0
associated O 0
with O 0
HIV B-Disease 0
disease I-Disease 0
progression O 0
. O 0

Our O 0
findings O 0
have O 0
implications O 0
for O 0
the O 0
provision O 0
of O 0
alcohol B-Chemical 0
use O 0
interventions O 0
and O 0
psychological O 0
resources O 0
to O 0
improve O 0
the O 0
health O 0
of O 0
women O 0
with O 0
HIV O 0
. O 0

Chemokine O 0
CCL2 O 0
and O 0
its O 0
receptor O 0
CCR2 O 0
are O 0
increased O 0
in O 0
the O 0
hippocampus O 0
following O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
status B-Disease 0
epilepticus I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Neuroinflammation B-Disease 0
occurs O 0
after O 0
seizures B-Disease 0
and O 0
is O 0
implicated O 0
in O 0
epileptogenesis O 0
. O 0

CCR2 O 0
is O 0
a O 0
chemokine O 0
receptor O 0
for O 0
CCL2 O 0
and O 0
their O 0
interaction O 0
mediates O 0
monocyte O 0
infiltration O 0
in O 0
the O 0
neuroinflammatory B-Disease 0
cascade O 0
triggered O 0
in O 0
different O 0
brain O 0
pathologies O 0
. O 0

In O 0
this O 0
work O 0
CCR2 O 0
and O 0
CCL2 O 0
expression O 0
were O 0
examined O 0
following O 0
status B-Disease 0
epilepticus I-Disease 0
( O 0
SE B-Disease 0
) O 0
induced O 0
by O 0
pilocarpine B-Chemical 0
injection O 0
. O 0

METHODS O 0
: O 0
SE B-Disease 0
was O 0
induced O 0
by O 0
pilocarpine B-Chemical 0
injection O 0
. O 0

Control O 0
rats O 0
were O 0
injected O 0
with O 0
saline O 0
instead O 0
of O 0
pilocarpine B-Chemical 0
. O 0

Five O 0
days O 0
after O 0
SE B-Disease 0
, O 0
CCR2 O 0
staining O 0
in O 0
neurons O 0
and O 0
glial O 0
cells O 0
was O 0
examined O 0
using O 0
imunohistochemical O 0
analyses O 0
. O 0

The O 0
number O 0
of O 0
CCR2 O 0
positive O 0
cells O 0
was O 0
determined O 0
using O 0
stereology O 0
probes O 0
in O 0
the O 0
hippocampus O 0
. O 0

CCL2 O 0
expression O 0
in O 0
the O 0
hippocampus O 0
was O 0
examined O 0
by O 0
molecular O 0
assay O 0
. O 0

RESULTS O 0
: O 0
Increased O 0
CCR2 O 0
was O 0
observed O 0
in O 0
the O 0
hippocampus O 0
after O 0
SE B-Disease 0
. O 0

Seizures B-Disease 0
also O 0
resulted O 0
in O 0
alterations O 0
to O 0
the O 0
cell O 0
types O 0
expressing O 0
CCR2 O 0
. O 0

Increased O 0
numbers O 0
of O 0
neurons O 0
that O 0
expressed O 0
CCR2 O 0
was O 0
observed O 0
following O 0
SE B-Disease 0
. O 0

Microglial O 0
cells O 0
were O 0
more O 0
closely O 0
apposed O 0
to O 0
the O 0
CCR2 O 0
- O 0
labeled O 0
cells O 0
in O 0
SE B-Disease 0
rats O 0
. O 0

In O 0
addition O 0
, O 0
rats O 0
that O 0
experienced O 0
SE B-Disease 0
exhibited O 0
CCR2 O 0
- O 0
labeling O 0
in O 0
populations O 0
of O 0
hypertrophied B-Disease 0
astrocytes O 0
, O 0
especially O 0
in O 0
CA1 O 0
and O 0
dentate O 0
gyrus O 0
. O 0

These O 0
CCR2 O 0
+ O 0
astroctytes O 0
were O 0
not O 0
observed O 0
in O 0
control O 0
rats O 0
. O 0

Examination O 0
of O 0
CCL2 O 0
expression O 0
showed O 0
that O 0
it O 0
was O 0
elevated O 0
in O 0
the O 0
hippocampus O 0
following O 0
SE B-Disease 0
. O 0

CONCLUSION O 0
: O 0
The O 0
data O 0
show O 0
that O 0
CCR2 O 0
and O 0
CCL2 O 0
are O 0
up O 0
- O 0
regulated O 0
in O 0
the O 0
hippocampus O 0
after O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
SE B-Disease 0
. O 0

Seizures B-Disease 0
also O 0
result O 0
in O 0
changes O 0
to O 0
CCR2 O 0
receptor O 0
expression O 0
in O 0
neurons O 0
and O 0
astrocytes O 0
. O 0

These O 0
changes O 0
might O 0
be O 0
involved O 0
in O 0
detrimental O 0
neuroplasticity O 0
and O 0
neuroinflammatory B-Disease 0
changes O 0
that O 0
occur O 0
following O 0
seizures B-Disease 0
. O 0

Metallothionein B-Chemical 0
induction O 0
reduces O 0
caspase O 0
- O 0
3 O 0
activity O 0
and O 0
TNFalpha O 0
levels O 0
with O 0
preservation O 0
of O 0
cognitive O 0
function O 0
and O 0
intact O 0
hippocampal O 0
neurons O 0
in O 0
carmustine B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

Hippocampal O 0
integrity O 0
is O 0
essential O 0
for O 0
cognitive O 0
functions O 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
induction O 0
of O 0
metallothionein B-Chemical 0
( O 0
MT B-Chemical 0
) O 0
by O 0
ZnSO B-Chemical 0
( I-Chemical 0
4 I-Chemical 0
) I-Chemical 0
and O 0
its O 0
role O 0
in O 0
neuroprotection O 0
has O 0
been O 0
documented O 0
. O 0

The O 0
present O 0
study O 0
aimed O 0
to O 0
explore O 0
the O 0
effect O 0
of O 0
MT B-Chemical 0
induction O 0
on O 0
carmustine B-Chemical 0
( O 0
BCNU B-Chemical 0
) O 0
- O 0
induced O 0
hippocampal O 0
cognitive B-Disease 0
dysfunction I-Disease 0
in O 0
rats O 0
. O 0

A O 0
total O 0
of O 0
60 O 0
male O 0
Wistar O 0
albino O 0
rats O 0
were O 0
randomly O 0
divided O 0
into O 0
four O 0
groups O 0
( O 0
15 O 0
/ O 0
group O 0
) O 0
: O 0
The O 0
control O 0
group O 0
injected O 0
with O 0
single O 0
doses O 0
of O 0
normal O 0
saline O 0
( O 0
i O 0
. O 0
c O 0
. O 0
v O 0
) O 0
followed O 0
24 O 0
h O 0
later O 0
by O 0
BCNU B-Chemical 0
solvent O 0
( O 0
i O 0
. O 0
v O 0
) O 0
. O 0

The O 0
second O 0
group O 0
administered O 0
ZnSO B-Chemical 0
( I-Chemical 0
4 I-Chemical 0
) I-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
micromol O 0
/ O 0
10 O 0
microl O 0
normal O 0
saline O 0
, O 0
i O 0
. O 0
c O 0
. O 0
v O 0
, O 0
once O 0
) O 0
then O 0
BCNU B-Chemical 0
solvent O 0
( O 0
i O 0
. O 0
v O 0
) O 0
after O 0
24 O 0
h O 0
. O 0

Third O 0
group O 0
received O 0
BCNU B-Chemical 0
( O 0
20 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
v O 0
, O 0
once O 0
) O 0
24 O 0
h O 0
after O 0
injection O 0
with O 0
normal O 0
saline O 0
( O 0
i O 0
. O 0
c O 0
. O 0
v O 0
) O 0
. O 0

Fourth O 0
group O 0
received O 0
a O 0
single O 0
dose O 0
of O 0
ZnSO B-Chemical 0
( I-Chemical 0
4 I-Chemical 0
) I-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
micromol O 0
/ O 0
10 O 0
microl O 0
normal O 0
saline O 0
, O 0
i O 0
. O 0
c O 0
. O 0
v O 0
) O 0
then O 0
BCNU B-Chemical 0
( O 0
20 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
v O 0
, O 0
once O 0
) O 0
after O 0
24 O 0
h O 0
. O 0

The O 0
obtained O 0
data O 0
revealed O 0
that O 0
BCNU B-Chemical 0
administration O 0
resulted O 0
in O 0
deterioration B-Disease 0
of I-Disease 0
learning I-Disease 0
and I-Disease 0
short I-Disease 0
- I-Disease 0
term I-Disease 0
memory I-Disease 0
( O 0
STM O 0
) O 0
, O 0
as O 0
measured O 0
by O 0
using O 0
radial O 0
arm O 0
water O 0
maze O 0
, O 0
accompanied O 0
with O 0
decreased O 0
hippocampal O 0
glutathione B-Chemical 0
reductase O 0
( O 0
GR O 0
) O 0
activity O 0
and O 0
reduced O 0
glutathione B-Chemical 0
( O 0
GSH B-Chemical 0
) O 0
content O 0
. O 0

Also O 0
, O 0
BCNU B-Chemical 0
administration O 0
increased O 0
serum O 0
tumor B-Disease 0
necrosis B-Disease 0
factor O 0
- O 0
alpha O 0
( O 0
TNFalpha O 0
) O 0
, O 0
hippocampal O 0
MT B-Chemical 0
and O 0
malondialdehyde B-Chemical 0
( O 0
MDA B-Chemical 0
) O 0
contents O 0
as O 0
well O 0
as O 0
caspase O 0
- O 0
3 O 0
activity O 0
in O 0
addition O 0
to O 0
histological O 0
alterations O 0
. O 0

ZnSO B-Chemical 0
( I-Chemical 0
4 I-Chemical 0
) I-Chemical 0
pretreatment O 0
counteracted O 0
BCNU B-Chemical 0
- O 0
induced O 0
inhibition O 0
of O 0
GR O 0
and O 0
depletion O 0
of O 0
GSH B-Chemical 0
and O 0
resulted O 0
in O 0
significant O 0
reduction O 0
in O 0
the O 0
levels O 0
of O 0
MDA B-Chemical 0
and O 0
TNFalpha O 0
as O 0
well O 0
as O 0
the O 0
activity O 0
of O 0
caspase O 0
- O 0
3 O 0
. O 0

The O 0
histological O 0
features O 0
were O 0
improved O 0
in O 0
hippocampus O 0
of O 0
rats O 0
treated O 0
with O 0
ZnSO B-Chemical 0
( I-Chemical 0
4 I-Chemical 0
) I-Chemical 0
+ O 0
BCNU B-Chemical 0
compared O 0
to O 0
only O 0
BCNU B-Chemical 0
- O 0
treated O 0
animals O 0
. O 0

In O 0
conclusion O 0
, O 0
MT B-Chemical 0
induction O 0
halts O 0
BCNU B-Chemical 0
- O 0
induced O 0
hippocampal O 0
toxicity B-Disease 0
as O 0
it O 0
prevented O 0
GR O 0
inhibition O 0
and O 0
GSH B-Chemical 0
depletion O 0
and O 0
counteracted O 0
the O 0
increased O 0
levels O 0
of O 0
TNFalpha O 0
, O 0
MDA B-Chemical 0
and O 0
caspase O 0
- O 0
3 O 0
activity O 0
with O 0
subsequent O 0
preservation O 0
of O 0
cognition O 0
. O 0

Fatal O 0
carbamazepine B-Chemical 0
induced O 0
fulminant B-Disease 0
eosinophilic I-Disease 0
( O 0
hypersensitivity B-Disease 0
) O 0
myocarditis B-Disease 0
: O 0
emphasis O 0
on O 0
anatomical O 0
and O 0
histological O 0
characteristics O 0
, O 0
mechanisms O 0
and O 0
genetics O 0
of O 0
drug B-Disease 0
hypersensitivity I-Disease 0
and O 0
differential O 0
diagnosis O 0
. O 0

The O 0
most O 0
severe O 0
adverse O 0
reactions O 0
to O 0
carbamazepine B-Chemical 0
have O 0
been O 0
observed O 0
in O 0
the O 0
haemopoietic O 0
system O 0
, O 0
the O 0
liver O 0
and O 0
the O 0
cardiovascular O 0
system O 0
. O 0

A O 0
frequently O 0
fatal O 0
, O 0
although O 0
exceptionally O 0
rare O 0
side O 0
effect O 0
of O 0
carbamazepine B-Chemical 0
is O 0
necrotizing O 0
eosinophilic O 0
( O 0
hypersensitivity B-Disease 0
) O 0
myocarditis B-Disease 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
hypersensitivity B-Disease 0
myocarditis B-Disease 0
secondary O 0
to O 0
administration O 0
of O 0
carbamazepine B-Chemical 0
. O 0

Acute O 0
hypersensitivity B-Disease 0
myocarditis B-Disease 0
was O 0
not O 0
suspected O 0
clinically O 0
, O 0
and O 0
the O 0
diagnosis O 0
was O 0
made O 0
post O 0
- O 0
mortem O 0
. O 0

Histology O 0
revealed O 0
diffuse O 0
infiltration O 0
of O 0
the O 0
myocardium O 0
by O 0
eosinophils O 0
and O 0
lymphocytes O 0
with O 0
myocyte O 0
damage O 0
. O 0

Clinically O 0
, O 0
death O 0
was O 0
due O 0
to O 0
cardiogenic B-Disease 0
shock I-Disease 0
. O 0

To O 0
best O 0
of O 0
our O 0
knowledge O 0
this O 0
is O 0
the O 0
second O 0
case O 0
of O 0
fatal O 0
carbamazepine B-Chemical 0
induced O 0
myocarditis B-Disease 0
reported O 0
in O 0
English O 0
literature O 0
. O 0

Neuropsychiatric O 0
behaviors O 0
in O 0
the O 0
MPTP B-Chemical 0
marmoset O 0
model O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

OBJECTIVES O 0
: O 0
Neuropsychiatric O 0
symptoms O 0
are O 0
increasingly O 0
recognised O 0
as O 0
a O 0
significant O 0
problem O 0
in O 0
patients O 0
with O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
( O 0
PD B-Disease 0
) O 0
. O 0

These O 0
symptoms O 0
may O 0
be O 0
due O 0
to O 0
' O 0
sensitisation O 0
' O 0
following O 0
repeated O 0
levodopa B-Chemical 0
treatment O 0
or O 0
a O 0
direct O 0
effect O 0
of O 0
dopamine B-Chemical 0
on O 0
the O 0
disease O 0
state O 0
. O 0

The O 0
levodopa B-Chemical 0
- O 0
treated O 0
MPTP B-Chemical 0
- O 0
lesioned O 0
marmoset O 0
was O 0
used O 0
as O 0
a O 0
model O 0
of O 0
neuropsychiatric B-Disease 0
symptoms I-Disease 0
in O 0
PD B-Disease 0
patients O 0
. O 0

Here O 0
we O 0
compare O 0
the O 0
time O 0
course O 0
of O 0
levodopa B-Chemical 0
- O 0
induced O 0
motor O 0
fluctuations O 0
and O 0
neuropsychiatric B-Disease 0
- I-Disease 0
like I-Disease 0
behaviors I-Disease 0
to O 0
determine O 0
the O 0
relationship O 0
between O 0
duration O 0
of O 0
treatment O 0
and O 0
onset O 0
of O 0
symptoms O 0
. O 0

METHODS O 0
: O 0
Marmosets O 0
were O 0
administered O 0
1 B-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
- I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
phenyl I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
2 I-Chemical 0
, I-Chemical 0
3 I-Chemical 0
, I-Chemical 0
6 I-Chemical 0
- I-Chemical 0
tetrahydropyridine I-Chemical 0
( O 0
2 O 0
. O 0
0 O 0
mg O 0
/ O 0
kg O 0
s O 0
. O 0
c O 0
. O 0
) O 0
for O 0
five O 0
days O 0
, O 0
resulting O 0
in O 0
stable O 0
parkinsonism B-Disease 0
. O 0

Levodopa B-Chemical 0
( O 0
15 O 0
mg O 0
/ O 0
kg O 0
and O 0
benserazide B-Chemical 0
, O 0
3 O 0
. O 0
75 O 0
mg O 0
/ O 0
kg O 0
) O 0
p O 0
. O 0
o O 0
. O 0

b O 0
. O 0
i O 0
. O 0
d O 0
, O 0
was O 0
administered O 0
for O 0
30 O 0
days O 0
. O 0

Animals O 0
were O 0
evaluated O 0
for O 0
parkinsonian B-Disease 0
disability I-Disease 0
, O 0
dyskinesia B-Disease 0
and O 0
on O 0
- O 0
time O 0
( O 0
motor O 0
fluctuations O 0
) O 0
and O 0
neuropsychiatric B-Disease 0
- I-Disease 0
like I-Disease 0
behaviors I-Disease 0
on O 0
Day O 0
0 O 0
( O 0
prior O 0
to O 0
levodopa B-Chemical 0
) O 0
and O 0
on O 0
Days O 0
1 O 0
, O 0
7 O 0
, O 0
13 O 0
, O 0
27 O 0
and O 0
30 O 0
of O 0
treatment O 0
using O 0
post O 0
hoc O 0
DVD O 0
analysis O 0
by O 0
a O 0
trained O 0
rater O 0
, O 0
blind O 0
to O 0
the O 0
treatment O 0
day O 0
. O 0

RESULTS O 0
: O 0
The O 0
neuropsychiatric B-Disease 0
- I-Disease 0
like I-Disease 0
behavior I-Disease 0
rating O 0
scale O 0
demonstrated O 0
high O 0
interrater O 0
reliability O 0
between O 0
three O 0
trained O 0
raters O 0
of O 0
differing O 0
professional O 0
backgrounds O 0
. O 0

As O 0
anticipated O 0
, O 0
animals O 0
exhibited O 0
a O 0
progressive O 0
increase O 0
in O 0
levodopa B-Chemical 0
- O 0
induced O 0
motor O 0
fluctuations O 0
, O 0
dyskinesia B-Disease 0
and O 0
wearing O 0
- O 0
off O 0
, O 0
that O 0
correlated O 0
with O 0
the O 0
duration O 0
of O 0
levodopa B-Chemical 0
therapy O 0
. O 0

In O 0
contrast O 0
, O 0
levodopa B-Chemical 0
- O 0
induced O 0
neuropsychiatric B-Disease 0
- I-Disease 0
like I-Disease 0
behaviors I-Disease 0
were O 0
present O 0
on O 0
Day O 0
1 O 0
of O 0
levodopa B-Chemical 0
treatment O 0
and O 0
their O 0
severity O 0
did O 0
not O 0
correlate O 0
with O 0
duration O 0
of O 0
treatment O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
data O 0
suggest O 0
that O 0
neuropsychiatric B-Disease 0
disorders I-Disease 0
in O 0
PD B-Disease 0
are O 0
more O 0
likely O 0
an O 0
interaction O 0
between O 0
levodopa B-Chemical 0
and O 0
the O 0
disease O 0
state O 0
than O 0
a O 0
consequence O 0
of O 0
sensitisation O 0
to O 0
repeated O 0
dopaminergic O 0
therapy O 0
. O 0

Contrast B-Chemical 0
medium I-Chemical 0
nephrotoxicity B-Disease 0
after O 0
renal O 0
artery O 0
and O 0
coronary O 0
angioplasty O 0
. O 0

BACKGROUND O 0
: O 0
Renal B-Disease 0
dysfunction I-Disease 0
induced O 0
by O 0
iodinated O 0
contrast B-Chemical 0
medium I-Chemical 0
( O 0
CM B-Chemical 0
) O 0
administration O 0
can O 0
minimize O 0
the O 0
benefit O 0
of O 0
the O 0
interventional O 0
procedure O 0
in O 0
patients O 0
undergoing O 0
renal O 0
angioplasty O 0
( O 0
PTRA O 0
) O 0
. O 0

PURPOSE O 0
: O 0
To O 0
compare O 0
the O 0
susceptibility O 0
to O 0
nephrotoxic B-Disease 0
effect O 0
of O 0
CM B-Chemical 0
in O 0
patients O 0
undergoing O 0
PTRA O 0
with O 0
that O 0
of O 0
patients O 0
submitted O 0
to O 0
percutaneous O 0
coronary O 0
intervention O 0
( O 0
PCI O 0
) O 0
. O 0

MATERIAL O 0
AND O 0
METHODS O 0
: O 0
A O 0
total O 0
of O 0
33 O 0
patients O 0
successfully O 0
treated O 0
with O 0
PTRA O 0
( O 0
PTRA O 0
group O 0
, O 0
mean O 0
age O 0
70 O 0
+ O 0
/ O 0
- O 0
12 O 0
years O 0
, O 0
23 O 0
female O 0
, O 0
basal O 0
creatinine B-Chemical 0
1 O 0
. O 0
46 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
79 O 0
, O 0
range O 0
0 O 0
. O 0
7 O 0
- O 0
4 O 0
. O 0
9 O 0
mg O 0
/ O 0
dl O 0
) O 0
were O 0
compared O 0
with O 0
33 O 0
patients O 0
undergoing O 0
successful O 0
PCI O 0
( O 0
PCI O 0
group O 0
) O 0
, O 0
matched O 0
for O 0
basal O 0
creatinine B-Chemical 0
( O 0
1 O 0
. O 0
44 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
6 O 0
, O 0
range O 0
0 O 0
. O 0
7 O 0
- O 0
3 O 0
. O 0
4 O 0
mg O 0
/ O 0
dl O 0
) O 0
, O 0
gender O 0
, O 0
and O 0
age O 0
. O 0

In O 0
both O 0
groups O 0
postprocedural O 0
( O 0
48 O 0
h O 0
) O 0
serum O 0
creatinine B-Chemical 0
was O 0
measured O 0
. O 0

RESULTS O 0
: O 0
Postprocedural O 0
creatinine B-Chemical 0
level O 0
decreased O 0
nonsignificantly O 0
in O 0
the O 0
PTRA O 0
group O 0
( O 0
1 O 0
. O 0
46 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
8 O 0
vs O 0
. O 0
1 O 0
. O 0
34 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
5 O 0
mg O 0
/ O 0
dl O 0
, O 0
P O 0
= O 0
NS O 0
) O 0
and O 0
increased O 0
significantly O 0
in O 0
the O 0
PCI O 0
group O 0
( O 0
1 O 0
. O 0
44 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
6 O 0
vs O 0
. O 0
1 O 0
. O 0
57 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
7 O 0
mg O 0
/ O 0
dl O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
02 O 0
) O 0
. O 0

Changes O 0
in O 0
serum O 0
creatinine B-Chemical 0
after O 0
intervention O 0
( O 0
after O 0
- O 0
before O 0
) O 0
were O 0
significantly O 0
different O 0
between O 0
the O 0
PTRA O 0
and O 0
PCI O 0
groups O 0
( O 0
- O 0
0 O 0
. O 0
12 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
5 O 0
vs O 0
. O 0
0 O 0
. O 0
13 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
3 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
014 O 0
) O 0
. O 0

This O 0
difference O 0
was O 0
not O 0
related O 0
to O 0
either O 0
a O 0
different O 0
clinical O 0
risk O 0
profile O 0
or O 0
to O 0
the O 0
volume O 0
of O 0
CM B-Chemical 0
administered O 0
. O 0

CONCLUSION O 0
: O 0
In O 0
this O 0
preliminary O 0
study O 0
patients O 0
submitted O 0
to O 0
PTRA O 0
showed O 0
a O 0
lower O 0
susceptibility O 0
to O 0
renal B-Disease 0
damage I-Disease 0
induced O 0
by O 0
CM B-Chemical 0
administration O 0
than O 0
PCI O 0
patients O 0
. O 0

The O 0
effectiveness O 0
of O 0
PTRA O 0
on O 0
renal O 0
function O 0
seems O 0
to O 0
be O 0
barely O 0
influenced O 0
by O 0
CM B-Chemical 0
toxicity B-Disease 0
. O 0

Diphenhydramine B-Chemical 0
prevents O 0
the O 0
haemodynamic O 0
changes O 0
of O 0
cimetidine B-Chemical 0
in O 0
ICU O 0
patients O 0
. O 0

Cimetidine B-Chemical 0
, O 0
a O 0
histamine B-Chemical 0
2 O 0
( O 0
H2 O 0
) O 0
antagonist O 0
, O 0
produces O 0
a O 0
decrease O 0
in O 0
arterial O 0
pressure O 0
due O 0
to O 0
vasodilatation O 0
, O 0
especially O 0
in O 0
critically O 0
ill O 0
patients O 0
. O 0

This O 0
may O 0
be O 0
because O 0
cimetidine B-Chemical 0
acts O 0
as O 0
a O 0
histamine B-Chemical 0
agonist O 0
. O 0

We O 0
, O 0
therefore O 0
, O 0
investigated O 0
the O 0
effects O 0
of O 0
the O 0
histamine B-Chemical 0
1 O 0
( O 0
H1 O 0
) O 0
receptor O 0
antagonist O 0
, O 0
diphenhydramine B-Chemical 0
, O 0
on O 0
the O 0
haemodynamic O 0
changes O 0
observed O 0
after O 0
cimetidine B-Chemical 0
in O 0
ICU O 0
patients O 0
. O 0

Each O 0
patient O 0
was O 0
studied O 0
on O 0
two O 0
separate O 0
days O 0
. O 0

In O 0
a O 0
random O 0
fashion O 0
, O 0
they O 0
received O 0
cimetidine B-Chemical 0
200 O 0
mg O 0
iv O 0
on O 0
one O 0
day O 0
, O 0
and O 0
on O 0
the O 0
other O 0
, O 0
a O 0
pretreatment O 0
of O 0
diphenhydramine B-Chemical 0
40 O 0
mg O 0
iv O 0
with O 0
cimetidine B-Chemical 0
200 O 0
mg O 0
iv O 0
. O 0

In O 0
the O 0
non O 0
- O 0
pretreatment O 0
group O 0
, O 0
mean O 0
arterial O 0
pressure O 0
( O 0
MAP O 0
) O 0
decreased O 0
from O 0
107 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
8 O 0
. O 0
4 O 0
mmHg O 0
to O 0
86 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
11 O 0
. O 0
4 O 0
mmHg O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
two O 0
minutes O 0
after O 0
cimetidine B-Chemical 0
. O 0

Also O 0
, O 0
systemic O 0
vascular O 0
resistance O 0
( O 0
SVR O 0
) O 0
decreased O 0
during O 0
the O 0
eight O 0
- O 0
minute O 0
observation O 0
period O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

In O 0
contrast O 0
, O 0
in O 0
the O 0
pretreatment O 0
group O 0
, O 0
little O 0
haemodynamic O 0
change O 0
was O 0
seen O 0
. O 0

We O 0
conclude O 0
that O 0
an O 0
H1 O 0
antagonist O 0
may O 0
be O 0
useful O 0
in O 0
preventing O 0
hypotension B-Disease 0
caused O 0
by O 0
iv O 0
cimetidine B-Chemical 0
, O 0
since O 0
the O 0
vasodilating O 0
activity O 0
of O 0
cimetidine B-Chemical 0
is O 0
mediated O 0
, O 0
in O 0
part O 0
, O 0
through O 0
the O 0
H1 O 0
receptor O 0
. O 0

Medical O 0
and O 0
psychiatric O 0
outcomes O 0
for O 0
patients O 0
transplanted O 0
for O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
: O 0
a O 0
case O 0
- O 0
control O 0
study O 0
. O 0

BACKGROUND O 0
: O 0
Acetaminophen B-Chemical 0
- O 0
induced O 0
hepatotoxicity B-Disease 0
is O 0
the O 0
most O 0
common O 0
cause O 0
of O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
( O 0
ALF B-Disease 0
) O 0
in O 0
the O 0
UK O 0
. O 0

Patients O 0
often O 0
consume O 0
the O 0
drug O 0
with O 0
suicidal O 0
intent O 0
or O 0
with O 0
a O 0
background O 0
of O 0
substance O 0
dependence O 0
. O 0

AIMS O 0
AND O 0
METHODS O 0
: O 0
We O 0
compared O 0
the O 0
severity O 0
of O 0
pretransplant O 0
illness O 0
, O 0
psychiatric O 0
co O 0
- O 0
morbidity O 0
, O 0
medical O 0
and O 0
psychosocial O 0
outcomes O 0
of O 0
all O 0
patients O 0
who O 0
had O 0
undergone O 0
liver O 0
transplantation O 0
( O 0
LT O 0
) O 0
emergently O 0
between O 0
1999 O 0
- O 0
2004 O 0
for O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
( O 0
n O 0
= O 0
36 O 0
) O 0
with O 0
age O 0
- O 0
and O 0
sex O 0
- O 0
matched O 0
patients O 0
undergoing O 0
emergent O 0
LT O 0
for O 0
non O 0
- O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
( O 0
n O 0
= O 0
35 O 0
) O 0
and O 0
elective O 0
LT O 0
for O 0
chronic B-Disease 0
liver I-Disease 0
disease I-Disease 0
( O 0
CLD B-Disease 0
, O 0
n O 0
= O 0
34 O 0
) O 0
. O 0

RESULTS O 0
: O 0
Acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
patients O 0
undergoing O 0
LT O 0
had O 0
a O 0
greater O 0
severity O 0
of O 0
pre O 0
- O 0
LT O 0
illness O 0
reflected O 0
by O 0
higher O 0
Acute O 0
Physiology O 0
and O 0
Chronic O 0
Health O 0
Evaluation O 0
II O 0
scores O 0
and O 0
requirement O 0
for O 0
organ O 0
support O 0
compared O 0
with O 0
the O 0
other O 0
two O 0
groups O 0
. O 0

Twenty O 0
( O 0
56 O 0
% O 0
) O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
patients O 0
had O 0
a O 0
formal O 0
psychiatric O 0
diagnosis O 0
before O 0
LT O 0
( O 0
non O 0
- O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
= O 0
0 O 0
/ O 0
35 O 0
, O 0
CLD B-Disease 0
= O 0
2 O 0
/ O 0
34 O 0
; O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
for O 0
all O 0
) O 0
and O 0
nine O 0
( O 0
25 O 0
% O 0
) O 0
had O 0
a O 0
previous O 0
suicide O 0
attempt O 0
. O 0

During O 0
follow O 0
- O 0
up O 0
( O 0
median O 0
5 O 0
years O 0
) O 0
, O 0
there O 0
were O 0
no O 0
significant O 0
differences O 0
in O 0
rejection O 0
( O 0
acute O 0
and O 0
chronic O 0
) O 0
, O 0
graft O 0
failure O 0
or O 0
survival O 0
between O 0
the O 0
groups O 0
( O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
1 O 0
year O 0
87 O 0
% O 0
, O 0
5 O 0
years O 0
75 O 0
% O 0
; O 0
non O 0
- O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
88 O 0
% O 0
, O 0
78 O 0
% O 0
; O 0
CLD B-Disease 0
93 O 0
% O 0
, O 0
82 O 0
% O 0
: O 0
P O 0
> O 0
0 O 0
. O 0
6 O 0
log O 0
rank O 0
) O 0
. O 0

Two O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
patients O 0
reattempted O 0
suicide O 0
post O 0
- O 0
LT O 0
( O 0
one O 0
died O 0
8 O 0
years O 0
post O 0
- O 0
LT O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Despite O 0
a O 0
high O 0
prevalence O 0
of O 0
psychiatric O 0
disturbance O 0
, O 0
outcomes O 0
for O 0
patients O 0
transplanted O 0
emergently O 0
for O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
were O 0
comparable O 0
to O 0
those O 0
transplanted O 0
for O 0
non O 0
- O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
ALF B-Disease 0
and O 0
electively O 0
for O 0
CLD B-Disease 0
. O 0

Multidisciplinary O 0
approaches O 0
with O 0
long O 0
- O 0
term O 0
psychiatric O 0
follow O 0
- O 0
up O 0
may O 0
contribute O 0
to O 0
low O 0
post O 0
- O 0
transplant O 0
suicide O 0
rates O 0
seen O 0
and O 0
low O 0
rates O 0
of O 0
graft O 0
loss O 0
because O 0
of O 0
non O 0
- O 0
compliance O 0
. O 0

Antithrombotic O 0
drug O 0
use O 0
, O 0
cerebral B-Disease 0
microbleeds I-Disease 0
, O 0
and O 0
intracerebral B-Disease 0
hemorrhage I-Disease 0
: O 0
a O 0
systematic O 0
review O 0
of O 0
published O 0
and O 0
unpublished O 0
studies O 0
. O 0

BACKGROUND O 0
AND O 0
PURPOSE O 0
: O 0
Cerebral B-Disease 0
microbleeds I-Disease 0
( O 0
MB B-Disease 0
) O 0
are O 0
potential O 0
risk O 0
factors O 0
for O 0
intracerebral B-Disease 0
hemorrhage I-Disease 0
( O 0
ICH B-Disease 0
) O 0
, O 0
but O 0
it O 0
is O 0
unclear O 0
if O 0
they O 0
are O 0
a O 0
contraindication O 0
to O 0
using O 0
antithrombotic O 0
drugs O 0
. O 0

Insights O 0
could O 0
be O 0
gained O 0
by O 0
pooling O 0
data O 0
on O 0
MB B-Disease 0
frequency O 0
stratified O 0
by O 0
antithrombotic O 0
use O 0
in O 0
cohorts O 0
with O 0
ICH B-Disease 0
and O 0
ischemic B-Disease 0
stroke I-Disease 0
( O 0
IS B-Disease 0
) O 0
/ O 0
transient B-Disease 0
ischemic I-Disease 0
attack I-Disease 0
( O 0
TIA B-Disease 0
) O 0
. O 0

METHODS O 0
: O 0
We O 0
performed O 0
a O 0
systematic O 0
review O 0
of O 0
published O 0
and O 0
unpublished O 0
data O 0
from O 0
cohorts O 0
with O 0
stroke B-Disease 0
or O 0
TIA B-Disease 0
to O 0
compare O 0
the O 0
presence O 0
of O 0
MB B-Disease 0
in O 0
: O 0
( O 0
1 O 0
) O 0
antithrombotic O 0
users O 0
vs O 0
nonantithrombotic O 0
users O 0
with O 0
ICH B-Disease 0
; O 0
( O 0
2 O 0
) O 0
antithrombotic O 0
users O 0
vs O 0
nonusers O 0
with O 0
IS B-Disease 0
/ O 0
TIA B-Disease 0
; O 0
and O 0
( O 0
3 O 0
) O 0
ICH B-Disease 0
vs O 0
ischemic B-Disease 0
events O 0
stratified O 0
by O 0
antithrombotic O 0
use O 0
. O 0

We O 0
also O 0
analyzed O 0
published O 0
and O 0
unpublished O 0
follow O 0
- O 0
up O 0
data O 0
to O 0
determine O 0
the O 0
risk O 0
of O 0
ICH B-Disease 0
in O 0
antithrombotic O 0
users O 0
with O 0
MB B-Disease 0
. O 0

RESULTS O 0
: O 0
In O 0
a O 0
pooled O 0
analysis O 0
of O 0
1460 O 0
ICH B-Disease 0
and O 0
3817 O 0
IS B-Disease 0
/ O 0
TIA B-Disease 0
, O 0
MB B-Disease 0
were O 0
more O 0
frequent O 0
in O 0
ICH B-Disease 0
vs O 0
IS B-Disease 0
/ O 0
TIA B-Disease 0
in O 0
all O 0
treatment O 0
groups O 0
, O 0
but O 0
the O 0
excess O 0
increased O 0
from O 0
2 O 0
. O 0
8 O 0
( O 0
odds O 0
ratio O 0
; O 0
range O 0
, O 0
2 O 0
. O 0
3 O 0
- O 0
3 O 0
. O 0
5 O 0
) O 0
in O 0
nonantithrombotic O 0
users O 0
to O 0
5 O 0
. O 0
7 O 0
( O 0
range O 0
, O 0
3 O 0
. O 0
4 O 0
- O 0
9 O 0
. O 0
7 O 0
) O 0
in O 0
antiplatelet O 0
users O 0
and O 0
8 O 0
. O 0
0 O 0
( O 0
range O 0
, O 0
3 O 0
. O 0
5 O 0
- O 0
17 O 0
. O 0
8 O 0
) O 0
in O 0
warfarin B-Chemical 0
users O 0
( O 0
P O 0
difference O 0
= O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

There O 0
was O 0
also O 0
an O 0
excess O 0
of O 0
MB B-Disease 0
in O 0
warfarin B-Chemical 0
users O 0
vs O 0
nonusers O 0
with O 0
ICH B-Disease 0
( O 0
OR O 0
, O 0
2 O 0
. O 0
7 O 0
; O 0
95 O 0
% O 0
CI O 0
, O 0
1 O 0
. O 0
6 O 0
- O 0
4 O 0
. O 0
4 O 0
; O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
but O 0
none O 0
in O 0
warfarin B-Chemical 0
users O 0
with O 0
IS B-Disease 0
/ O 0
TIA B-Disease 0
( O 0
OR O 0
, O 0
1 O 0
. O 0
3 O 0
; O 0
95 O 0
% O 0
CI O 0
, O 0
0 O 0
. O 0
9 O 0
- O 0
1 O 0
. O 0
7 O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
33 O 0
; O 0
P O 0
difference O 0
= O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

There O 0
was O 0
a O 0
smaller O 0
excess O 0
of O 0
MB B-Disease 0
in O 0
antiplatelet O 0
users O 0
vs O 0
nonusers O 0
with O 0
ICH B-Disease 0
( O 0
OR O 0
, O 0
1 O 0
. O 0
7 O 0
; O 0
95 O 0
% O 0
CI O 0
, O 0
1 O 0
. O 0
3 O 0
- O 0
2 O 0
. O 0
3 O 0
; O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
but O 0
findings O 0
were O 0
similar O 0
for O 0
antiplatelet O 0
users O 0
with O 0
IS B-Disease 0
/ O 0
TIA B-Disease 0
( O 0
OR O 0
, O 0
1 O 0
. O 0
4 O 0
; O 0
95 O 0
% O 0
CI O 0
, O 0
1 O 0
. O 0
2 O 0
- O 0
1 O 0
. O 0
7 O 0
; O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
; O 0
P O 0
difference O 0
= O 0
0 O 0
. O 0
25 O 0
) O 0
. O 0

In O 0
pooled O 0
follow O 0
- O 0
up O 0
data O 0
for O 0
768 O 0
antithrombotic O 0
users O 0
, O 0
presence O 0
of O 0
MB B-Disease 0
at O 0
baseline O 0
was O 0
associated O 0
with O 0
a O 0
substantially O 0
increased O 0
risk O 0
of O 0
subsequent O 0
ICH B-Disease 0
( O 0
OR O 0
, O 0
12 O 0
. O 0
1 O 0
; O 0
95 O 0
% O 0
CI O 0
, O 0
3 O 0
. O 0
4 O 0
- O 0
42 O 0
. O 0
5 O 0
; O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
excess O 0
of O 0
MB B-Disease 0
in O 0
warfarin B-Chemical 0
users O 0
with O 0
ICH B-Disease 0
compared O 0
to O 0
other O 0
groups O 0
suggests O 0
that O 0
MB B-Disease 0
increase O 0
the O 0
risk O 0
of O 0
warfarin B-Chemical 0
- O 0
associated O 0
ICH B-Disease 0
. O 0

Limited O 0
prospective O 0
data O 0
corroborate O 0
these O 0
findings O 0
, O 0
but O 0
larger O 0
prospective O 0
studies O 0
are O 0
urgently O 0
required O 0
. O 0

Studies O 0
of O 0
synergy O 0
between O 0
morphine B-Chemical 0
and O 0
a O 0
novel O 0
sodium B-Chemical 0
channel O 0
blocker O 0
, O 0
CNSB002 B-Chemical 0
, O 0
in O 0
rat O 0
models O 0
of O 0
inflammatory O 0
and O 0
neuropathic B-Disease 0
pain I-Disease 0
. O 0

OBJECTIVE O 0
: O 0
This O 0
study O 0
determined O 0
the O 0
antihyperalgesic O 0
effect O 0
of O 0
CNSB002 B-Chemical 0
, O 0
a O 0
sodium B-Chemical 0
channel O 0
blocker O 0
with O 0
antioxidant O 0
properties O 0
given O 0
alone O 0
and O 0
in O 0
combinations O 0
with O 0
morphine B-Chemical 0
in O 0
rat O 0
models O 0
of O 0
inflammatory O 0
and O 0
neuropathic B-Disease 0
pain I-Disease 0
. O 0

DESIGN O 0
: O 0
Dose O 0
response O 0
curves O 0
for O 0
nonsedating O 0
doses O 0
of O 0
morphine B-Chemical 0
and O 0
CNSB002 B-Chemical 0
given O 0
intraperitoneally O 0
alone O 0
and O 0
together O 0
in O 0
combinations O 0
were O 0
constructed O 0
for O 0
antihyperalgesic O 0
effect O 0
using O 0
paw O 0
withdrawal O 0
from O 0
noxious O 0
heat O 0
in O 0
two O 0
rat O 0
pain B-Disease 0
models O 0
: O 0
carrageenan B-Chemical 0
- O 0
induced O 0
paw O 0
inflammation B-Disease 0
and O 0
streptozotocin B-Chemical 0
( O 0
STZ B-Chemical 0
) O 0
- O 0
induced O 0
diabetic B-Disease 0
neuropathy I-Disease 0
. O 0

RESULTS O 0
: O 0
The O 0
maximum O 0
nonsedating O 0
doses O 0
were O 0
: O 0
morphine B-Chemical 0
, O 0
3 O 0
. O 0
2 O 0
mg O 0
/ O 0
kg O 0
; O 0
CNSB002 B-Chemical 0
10 O 0
. O 0
0 O 0
mg O 0
/ O 0
kg O 0
; O 0
5 O 0
. O 0
0 O 0
mg O 0
/ O 0
kg O 0
CNSB002 B-Chemical 0
with O 0
morphine B-Chemical 0
3 O 0
. O 0
2 O 0
mg O 0
/ O 0
kg O 0
in O 0
combination O 0
. O 0

The O 0
doses O 0
calculated O 0
to O 0
cause O 0
50 O 0
% O 0
reversal O 0
of O 0
hyperalgesia B-Disease 0
( O 0
ED50 O 0
) O 0
were O 0
7 O 0
. O 0
54 O 0
( O 0
1 O 0
. O 0
81 O 0
) O 0
and O 0
4 O 0
. O 0
83 O 0
( O 0
1 O 0
. O 0
54 O 0
) O 0
in O 0
the O 0
carrageenan B-Chemical 0
model O 0
and O 0
44 O 0
. O 0
18 O 0
( O 0
1 O 0
. O 0
37 O 0
) O 0
and O 0
9 O 0
. O 0
14 O 0
( O 0
1 O 0
. O 0
24 O 0
) O 0
in O 0
the O 0
STZ B-Chemical 0
- O 0
induced O 0
neuropathy B-Disease 0
model O 0
for O 0
CNSB002 B-Chemical 0
and O 0
morphine B-Chemical 0
, O 0
respectively O 0
( O 0
mg O 0
/ O 0
kg O 0
; O 0
mean O 0
, O 0
SEM O 0
) O 0
. O 0

These O 0
values O 0
were O 0
greater O 0
than O 0
the O 0
maximum O 0
nonsedating O 0
doses O 0
. O 0

The O 0
ED50 O 0
values O 0
for O 0
morphine B-Chemical 0
when O 0
given O 0
in O 0
combination O 0
with O 0
CNSB002 B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
were O 0
less O 0
than O 0
the O 0
maximum O 0
nonsedating O 0
dose O 0
: O 0
0 O 0
. O 0
56 O 0
( O 0
1 O 0
. O 0
55 O 0
) O 0
in O 0
the O 0
carrageenan B-Chemical 0
model O 0
and O 0
1 O 0
. O 0
37 O 0
( O 0
1 O 0
. O 0
23 O 0
) O 0
in O 0
the O 0
neuropathy B-Disease 0
model O 0
( O 0
mg O 0
/ O 0
kg O 0
; O 0
mean O 0
, O 0
SEM O 0
) O 0
. O 0

The O 0
antinociception O 0
after O 0
morphine B-Chemical 0
( O 0
3 O 0
. O 0
2 O 0
mg O 0
/ O 0
kg O 0
) O 0
was O 0
increased O 0
by O 0
co O 0
- O 0
administration O 0
with O 0
CNSB002 B-Chemical 0
from O 0
28 O 0
. O 0
0 O 0
and O 0
31 O 0
. O 0
7 O 0
% O 0
to O 0
114 O 0
. O 0
6 O 0
and O 0
56 O 0
. O 0
9 O 0
% O 0
reversal O 0
of O 0
hyperalgesia B-Disease 0
in O 0
the O 0
inflammatory O 0
and O 0
neuropathic B-Disease 0
models O 0
, O 0
respectively O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
; O 0
one O 0
- O 0
way O 0
analysis O 0
of O 0
variance O 0
- O 0
significantly O 0
greater O 0
than O 0
either O 0
drug O 0
given O 0
alone O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
maximum O 0
antihyperalgesic O 0
effect O 0
achievable O 0
with O 0
nonsedating O 0
doses O 0
of O 0
morphine B-Chemical 0
may O 0
be O 0
increased O 0
significantly O 0
when O 0
the O 0
drug O 0
is O 0
used O 0
in O 0
combination O 0
with O 0
CNSB002 B-Chemical 0
. O 0

Heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
: O 0
a O 0
practical O 0
review O 0
. O 0

Heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
( O 0
HIT B-Disease 0
) O 0
remains O 0
under O 0
- O 0
recognized O 0
despite O 0
its O 0
potentially O 0
devastating O 0
outcomes O 0
. O 0

It O 0
begins O 0
when O 0
heparin B-Chemical 0
exposure O 0
stimulates O 0
the O 0
formation O 0
of O 0
heparin B-Chemical 0
- O 0
platelet O 0
factor O 0
4 O 0
antibodies O 0
, O 0
which O 0
in O 0
turn O 0
triggers O 0
the O 0
release O 0
of O 0
procoagulant O 0
platelet O 0
particles O 0
. O 0

Thrombosis B-Disease 0
and O 0
thrombocytopenia B-Disease 0
that O 0
follow O 0
comprise O 0
the O 0
2 O 0
hallmark O 0
traits O 0
of O 0
HIT B-Disease 0
, O 0
with O 0
the O 0
former O 0
largely O 0
responsible O 0
for O 0
significant O 0
vascular O 0
complications O 0
. O 0

The O 0
prevalence O 0
of O 0
HIT B-Disease 0
varies O 0
among O 0
several O 0
subgroups O 0
, O 0
with O 0
greater O 0
incidence O 0
in O 0
surgical O 0
as O 0
compared O 0
with O 0
medical O 0
populations O 0
. O 0

HIT B-Disease 0
must O 0
be O 0
acknowledged O 0
for O 0
its O 0
intense O 0
predilection O 0
for O 0
thrombosis B-Disease 0
and O 0
suspected O 0
whenever O 0
thrombosis B-Disease 0
occurs O 0
after O 0
heparin B-Chemical 0
exposure O 0
. O 0

Early O 0
recognition O 0
that O 0
incorporates O 0
the O 0
clinical O 0
and O 0
serologic O 0
clues O 0
is O 0
paramount O 0
to O 0
timely O 0
institution O 0
of O 0
treatment O 0
, O 0
as O 0
its O 0
delay O 0
may O 0
result O 0
in O 0
catastrophic O 0
outcomes O 0
. O 0

The O 0
treatment O 0
of O 0
HIT B-Disease 0
mandates O 0
an O 0
immediate O 0
cessation O 0
of O 0
all O 0
heparin B-Chemical 0
exposure O 0
and O 0
the O 0
institution O 0
of O 0
an O 0
antithrombotic O 0
therapy O 0
, O 0
most O 0
commonly O 0
using O 0
a O 0
direct B-Chemical 0
thrombin I-Chemical 0
inhibitor I-Chemical 0
. O 0

Current O 0
" O 0
diagnostic O 0
" O 0
tests O 0
, O 0
which O 0
primarily O 0
include O 0
functional O 0
and O 0
antigenic O 0
assays O 0
, O 0
have O 0
more O 0
of O 0
a O 0
confirmatory O 0
than O 0
diagnostic O 0
role O 0
in O 0
the O 0
management O 0
of O 0
HIT B-Disease 0
. O 0

Special O 0
attention O 0
must O 0
be O 0
paid O 0
to O 0
cardiac O 0
patients O 0
who O 0
are O 0
often O 0
exposed O 0
to O 0
heparin B-Chemical 0
multiple O 0
times O 0
during O 0
their O 0
course O 0
of O 0
treatment O 0
. O 0

Direct B-Chemical 0
thrombin I-Chemical 0
inhibitors I-Chemical 0
are O 0
appropriate O 0
, O 0
evidence O 0
- O 0
based O 0
alternatives O 0
to O 0
heparin B-Chemical 0
in O 0
patients O 0
with O 0
a O 0
history O 0
of O 0
HIT B-Disease 0
, O 0
who O 0
need O 0
to O 0
undergo O 0
percutaneous O 0
coronary O 0
intervention O 0
. O 0

As O 0
heparin B-Chemical 0
remains O 0
one O 0
of O 0
the O 0
most O 0
frequently O 0
used O 0
medications O 0
today O 0
with O 0
potential O 0
for O 0
HIT B-Disease 0
with O 0
every O 0
heparin B-Chemical 0
exposure O 0
, O 0
a O 0
close O 0
vigilance O 0
of O 0
platelet O 0
counts O 0
must O 0
be O 0
practiced O 0
whenever O 0
heparin B-Chemical 0
is O 0
initiated O 0
. O 0

Abductor O 0
paralysis B-Disease 0
after O 0
botox B-Chemical 0
injection O 0
for O 0
adductor B-Disease 0
spasmodic I-Disease 0
dysphonia I-Disease 0
. O 0

OBJECTIVES O 0
/ O 0
HYPOTHESIS O 0
: O 0
Botulinum O 0
toxin O 0
( O 0
Botox B-Chemical 0
) O 0
injections O 0
into O 0
the O 0
thyroarytenoid O 0
muscles O 0
are O 0
the O 0
current O 0
standard O 0
of O 0
care O 0
for O 0
adductor B-Disease 0
spasmodic I-Disease 0
dysphonia I-Disease 0
( O 0
ADSD B-Disease 0
) O 0
. O 0

Reported O 0
adverse O 0
effects O 0
include O 0
a O 0
period O 0
of O 0
breathiness O 0
, O 0
throat B-Disease 0
pain I-Disease 0
, O 0
and O 0
difficulty O 0
with O 0
swallowing O 0
liquids O 0
. O 0

Here O 0
we O 0
report O 0
multiple O 0
cases O 0
of O 0
bilateral O 0
abductor O 0
paralysis B-Disease 0
following O 0
Botox B-Chemical 0
injections O 0
for O 0
ADSD B-Disease 0
, O 0
a O 0
complication O 0
previously O 0
unreported O 0
. O 0

STUDY O 0
DESIGN O 0
: O 0
Retrospective O 0
case O 0
series O 0
. O 0

METHODS O 0
: O 0
Patients O 0
that O 0
received O 0
Botox B-Chemical 0
injections O 0
for O 0
spasmodic B-Disease 0
dysphonia I-Disease 0
between O 0
January O 0
2000 O 0
and O 0
October O 0
2009 O 0
were O 0
evaluated O 0
. O 0

Patients O 0
with O 0
ADSD B-Disease 0
were O 0
identified O 0
. O 0

The O 0
number O 0
of O 0
treatments O 0
received O 0
and O 0
adverse O 0
effects O 0
were O 0
noted O 0
. O 0

For O 0
patients O 0
with O 0
bilateral O 0
abductor O 0
paralysis B-Disease 0
, O 0
age O 0
, O 0
sex O 0
, O 0
paralytic O 0
Botox B-Chemical 0
dose O 0
, O 0
prior O 0
Botox B-Chemical 0
dose O 0
, O 0
and O 0
course O 0
following O 0
paralysis B-Disease 0
were O 0
noted O 0
. O 0

RESULTS O 0
: O 0
From O 0
a O 0
database O 0
of O 0
452 O 0
patients O 0
receiving O 0
Botox B-Chemical 0
, O 0
352 O 0
patients O 0
had O 0
been O 0
diagnosed O 0
with O 0
ADSD B-Disease 0
. O 0

Of O 0
these O 0
352 O 0
patients O 0
, O 0
eight O 0
patients O 0
suffered O 0
bilateral O 0
abductor O 0
paralysis B-Disease 0
, O 0
and O 0
two O 0
suffered O 0
this O 0
complication O 0
twice O 0
. O 0

All O 0
affected O 0
patients O 0
were O 0
females O 0
over O 0
the O 0
age O 0
of O 0
50 O 0
years O 0
. O 0

Most O 0
patients O 0
had O 0
received O 0
treatments O 0
prior O 0
to O 0
abductor O 0
paralysis B-Disease 0
and O 0
continued O 0
receiving O 0
after O 0
paralysis B-Disease 0
. O 0

Seven O 0
patients O 0
recovered O 0
after O 0
a O 0
brief O 0
period O 0
of O 0
activity O 0
restrictions O 0
, O 0
and O 0
one O 0
underwent O 0
a O 0
tracheotomy O 0
. O 0

The O 0
incidence O 0
of O 0
abductor O 0
paralysis B-Disease 0
after O 0
Botox B-Chemical 0
injection O 0
for O 0
ADSD B-Disease 0
was O 0
0 O 0
. O 0
34 O 0
% O 0
. O 0

CONCLUSIONS O 0
: O 0
Bilateral O 0
abductor O 0
paralysis B-Disease 0
is O 0
a O 0
rare O 0
complication O 0
of O 0
Botox B-Chemical 0
injections O 0
for O 0
ADSD B-Disease 0
, O 0
causing O 0
difficulty O 0
with O 0
breathing O 0
upon O 0
exertion O 0
. O 0

The O 0
likely O 0
mechanism O 0
of O 0
paralysis B-Disease 0
is O 0
diffusion O 0
of O 0
Botox B-Chemical 0
around O 0
the O 0
muscular O 0
process O 0
of O 0
the O 0
arytenoid O 0
to O 0
the O 0
posterior O 0
cricoarytenoid O 0
muscles O 0
. O 0

The O 0
paralysis B-Disease 0
is O 0
temporary O 0
, O 0
and O 0
watchful O 0
waiting O 0
with O 0
restriction O 0
of O 0
activity O 0
is O 0
the O 0
recommended O 0
management O 0
. O 0

Mitochondrial B-Disease 0
impairment I-Disease 0
contributes O 0
to O 0
cocaine B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
dysfunction I-Disease 0
: O 0
Prevention O 0
by O 0
the O 0
targeted O 0
antioxidant O 0
MitoQ B-Chemical 0
. O 0

The O 0
goal O 0
of O 0
this O 0
study O 0
was O 0
to O 0
assess O 0
mitochondrial O 0
function O 0
and O 0
ROS O 0
production O 0
in O 0
an O 0
experimental O 0
model O 0
of O 0
cocaine B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
dysfunction I-Disease 0
. O 0

We O 0
hypothesized O 0
that O 0
cocaine B-Disease 0
abuse I-Disease 0
may O 0
lead O 0
to O 0
altered O 0
mitochondrial O 0
function O 0
that O 0
in O 0
turn O 0
may O 0
cause O 0
left B-Disease 0
ventricular I-Disease 0
dysfunction I-Disease 0
. O 0

Seven O 0
days O 0
of O 0
cocaine B-Chemical 0
administration O 0
to O 0
rats O 0
led O 0
to O 0
an O 0
increased O 0
oxygen B-Chemical 0
consumption O 0
detected O 0
in O 0
cardiac O 0
fibers O 0
, O 0
specifically O 0
through O 0
complex O 0
I O 0
and O 0
complex O 0
III O 0
. O 0

ROS O 0
levels O 0
were O 0
increased O 0
, O 0
specifically O 0
in O 0
interfibrillar O 0
mitochondria O 0
. O 0

In O 0
parallel O 0
there O 0
was O 0
a O 0
decrease O 0
in O 0
ATP B-Chemical 0
synthesis O 0
, O 0
whereas O 0
no O 0
difference O 0
was O 0
observed O 0
in O 0
subsarcolemmal O 0
mitochondria O 0
. O 0

This O 0
uncoupling O 0
effect O 0
on O 0
oxidative O 0
phosphorylation O 0
was O 0
not O 0
detectable O 0
after O 0
short O 0
- O 0
term O 0
exposure O 0
to O 0
cocaine B-Chemical 0
, O 0
suggesting O 0
that O 0
these O 0
mitochondrial B-Disease 0
abnormalities I-Disease 0
were O 0
a O 0
late O 0
rather O 0
than O 0
a O 0
primary O 0
event O 0
in O 0
the O 0
pathological O 0
response O 0
to O 0
cocaine B-Chemical 0
. O 0

MitoQ B-Chemical 0
, O 0
a O 0
mitochondrial O 0
- O 0
targeted O 0
antioxidant O 0
, O 0
was O 0
shown O 0
to O 0
completely O 0
prevent O 0
these O 0
mitochondrial B-Disease 0
abnormalities I-Disease 0
as O 0
well O 0
as O 0
cardiac B-Disease 0
dysfunction I-Disease 0
characterized O 0
here O 0
by O 0
a O 0
diastolic B-Disease 0
dysfunction I-Disease 0
studied O 0
with O 0
a O 0
conductance O 0
catheter O 0
to O 0
obtain O 0
pressure O 0
- O 0
volume O 0
data O 0
. O 0

Taken O 0
together O 0
, O 0
these O 0
results O 0
extend O 0
previous O 0
studies O 0
and O 0
demonstrate O 0
that O 0
cocaine B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
dysfunction I-Disease 0
may O 0
be O 0
due O 0
to O 0
a O 0
mitochondrial B-Disease 0
defect I-Disease 0
. O 0

Trimethoprim B-Chemical 0
- O 0
induced O 0
immune O 0
hemolytic B-Disease 0
anemia I-Disease 0
in O 0
a O 0
pediatric O 0
oncology O 0
patient O 0
presenting O 0
as O 0
an O 0
acute O 0
hemolytic O 0
transfusion O 0
reaction O 0
. O 0

A O 0
10 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
with O 0
acute B-Disease 0
leukemia I-Disease 0
presented O 0
with O 0
post O 0
- O 0
chemotherapy O 0
anemia B-Disease 0
. O 0

During O 0
red O 0
cell O 0
transfusion O 0
, O 0
he O 0
developed O 0
hemoglobinuria B-Disease 0
. O 0

Transfusion O 0
reaction O 0
workup O 0
was O 0
negative O 0
. O 0

Drug O 0
- O 0
induced O 0
immune O 0
hemolytic B-Disease 0
anemia I-Disease 0
was O 0
suspected O 0
because O 0
of O 0
positive O 0
direct O 0
antiglobulin O 0
test O 0
, O 0
negative O 0
eluate O 0
, O 0
and O 0
microspherocytes O 0
on O 0
smear O 0
pre O 0
- O 0
and O 0
post O 0
- O 0
transfusion O 0
. O 0

Drug O 0
studies O 0
using O 0
the O 0
indirect O 0
antiglobulin O 0
test O 0
were O 0
strongly O 0
positive O 0
with O 0
trimethoprim B-Chemical 0
and O 0
trimethoprim B-Chemical 0
- I-Chemical 0
sulfamethoxazole I-Chemical 0
but O 0
negative O 0
with O 0
sulfamethoxazole B-Chemical 0
. O 0

The O 0
patient O 0
recovered O 0
after O 0
discontinuing O 0
the O 0
drug O 0
, O 0
with O 0
no O 0
recurrence O 0
in O 0
2 O 0
years O 0
. O 0

Other O 0
causes O 0
of O 0
anemia B-Disease 0
should O 0
be O 0
considered O 0
in O 0
patients O 0
with O 0
worse O 0
- O 0
than O 0
- O 0
expected O 0
anemia B-Disease 0
after O 0
chemotherapy O 0
. O 0

Furthermore O 0
, O 0
hemolysis B-Disease 0
during O 0
transfusion O 0
is O 0
not O 0
always O 0
a O 0
transfusion O 0
reaction O 0
. O 0

Verapamil B-Chemical 0
stimulation O 0
test O 0
in O 0
hyperprolactinemia B-Disease 0
: O 0
loss O 0
of O 0
prolactin O 0
response O 0
in O 0
anatomic O 0
or O 0
functional O 0
stalk O 0
effect O 0
. O 0

AIM O 0
: O 0
Verapamil B-Chemical 0
stimulation O 0
test O 0
was O 0
previously O 0
investigated O 0
as O 0
a O 0
tool O 0
for O 0
differential O 0
diagnosis O 0
of O 0
hyperprolactinemia B-Disease 0
, O 0
but O 0
with O 0
conflicting O 0
results O 0
. O 0

Macroprolactinemia B-Disease 0
was O 0
never O 0
considered O 0
in O 0
those O 0
previous O 0
studies O 0
. O 0

Here O 0
, O 0
we O 0
aimed O 0
to O 0
re O 0
- O 0
investigate O 0
the O 0
diagnostic O 0
value O 0
of O 0
verapamil B-Chemical 0
in O 0
a O 0
population O 0
who O 0
were O 0
all O 0
screened O 0
for O 0
macroprolactinemia B-Disease 0
. O 0

Prolactin O 0
responses O 0
to O 0
verapamil B-Chemical 0
in O 0
65 O 0
female O 0
patients O 0
( O 0
age O 0
: O 0
29 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
8 O 0
. O 0
1 O 0
years O 0
) O 0
with O 0
hyperprolactinemia B-Disease 0
were O 0
tested O 0
in O 0
a O 0
descriptive O 0
, O 0
matched O 0
case O 0
- O 0
control O 0
study O 0
. O 0

METHODS O 0
: O 0
Verapamil B-Chemical 0
80 O 0
mg O 0
, O 0
p O 0
. O 0
o O 0
. O 0
was O 0
administered O 0
, O 0
and O 0
then O 0
PRL O 0
levels O 0
were O 0
measured O 0
at O 0
8th O 0
and O 0
16th O 0
hours O 0
, O 0
by O 0
immunometric O 0
chemiluminescence O 0
. O 0

Verapamil B-Chemical 0
responsiveness O 0
was O 0
determined O 0
by O 0
peak O 0
percent O 0
change O 0
in O 0
basal O 0
prolactin O 0
levels O 0
( O 0
PRL O 0
) O 0
. O 0

RESULTS O 0
: O 0
Verapamil B-Chemical 0
significantly O 0
increased O 0
PRL O 0
levels O 0
in O 0
healthy O 0
controls O 0
( O 0
N O 0
. O 0
8 O 0
, O 0
PRL O 0
: O 0
183 O 0
% O 0
) O 0
, O 0
macroprolactinoma B-Disease 0
( O 0
N O 0
. O 0
8 O 0
, O 0
PRL O 0
: O 0
7 O 0
% O 0
) O 0
, O 0
microprolactinoma B-Disease 0
( O 0
N O 0
. O 0
19 O 0
, O 0
PRL O 0
: O 0
21 O 0
% O 0
) O 0
, O 0
macroprolactinemia B-Disease 0
( O 0
N O 0
. O 0
23 O 0
, O 0
PRL O 0
: O 0
126 O 0
% O 0
) O 0
, O 0
but O 0
not O 0
in O 0
pseudoprolactinoma B-Disease 0
( O 0
N O 0
. O 0
8 O 0
, O 0
PRL O 0
: O 0
0 O 0
. O 0
8 O 0
% O 0
) O 0
, O 0
and O 0
risperidone B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
( O 0
N O 0
. O 0
7 O 0
, O 0
PRL O 0
: O 0
3 O 0
% O 0
) O 0
. O 0

ROC O 0
curve O 0
analysis O 0
revealed O 0
that O 0
unresponsiveness O 0
to O 0
verapamil B-Chemical 0
defined O 0
as O 0
PRL O 0
< O 0
7 O 0
% O 0
, O 0
discriminated O 0
anatomical O 0
or O 0
functional O 0
stalk O 0
effect O 0
( O 0
sensitivity O 0
: O 0
74 O 0
% O 0
, O 0
specificity O 0
: O 0
73 O 0
% O 0
, O 0
AUC O 0
: O 0
0 O 0
. O 0
855 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
04 O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
, O 0
CI O 0
: O 0
0 O 0
. O 0
768 O 0
- O 0
0 O 0
. O 0
942 O 0
) O 0
associated O 0
with O 0
pseudoprolactinoma B-Disease 0
or O 0
risperidone B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
, O 0
respectively O 0
. O 0

CONCLUSION O 0
: O 0
Verapamil B-Chemical 0
responsiveness O 0
is O 0
not O 0
a O 0
reliable O 0
finding O 0
for O 0
the O 0
differential O 0
diagnosis O 0
of O 0
hyperprolactinemia B-Disease 0
. O 0

However O 0
, O 0
verapamil B-Chemical 0
unresponsiveness O 0
discriminates O 0
stalk O 0
effect O 0
( O 0
i O 0
. O 0
e O 0
. O 0
, O 0
anatomically O 0
or O 0
functionally O 0
inhibited O 0
dopaminergic O 0
tonus O 0
) O 0
from O 0
other O 0
causes O 0
of O 0
hyperprolactinemia B-Disease 0
with O 0
varying O 0
degrees O 0
of O 0
responsiveness O 0
. O 0

Blockade O 0
of O 0
endothelial O 0
- O 0
mesenchymal O 0
transition O 0
by O 0
a O 0
Smad3 O 0
inhibitor O 0
delays O 0
the O 0
early O 0
development O 0
of O 0
streptozotocin B-Chemical 0
- O 0
induced O 0
diabetic B-Disease 0
nephropathy I-Disease 0
. O 0

OBJECTIVE O 0
: O 0
A O 0
multicenter O 0
, O 0
controlled O 0
trial O 0
showed O 0
that O 0
early O 0
blockade O 0
of O 0
the O 0
renin O 0
- O 0
angiotensin B-Chemical 0
system O 0
in O 0
patients O 0
with O 0
type B-Disease 0
1 I-Disease 0
diabetes I-Disease 0
and O 0
normoalbuminuria O 0
did O 0
not O 0
retard O 0
the O 0
progression O 0
of O 0
nephropathy B-Disease 0
, O 0
suggesting O 0
that O 0
other O 0
mechanism O 0
( O 0
s O 0
) O 0
are O 0
involved O 0
in O 0
the O 0
pathogenesis O 0
of O 0
early O 0
diabetic B-Disease 0
nephropathy I-Disease 0
( O 0
diabetic B-Disease 0
nephropathy I-Disease 0
) O 0
. O 0

We O 0
have O 0
previously O 0
demonstrated O 0
that O 0
endothelial O 0
- O 0
mesenchymal O 0
- O 0
transition O 0
( O 0
EndoMT O 0
) O 0
contributes O 0
to O 0
the O 0
early O 0
development O 0
of O 0
renal O 0
interstitial O 0
fibrosis B-Disease 0
independently O 0
of O 0
microalbuminuria O 0
in O 0
mice O 0
with O 0
streptozotocin B-Chemical 0
( O 0
STZ B-Chemical 0
) O 0
- O 0
induced O 0
diabetes B-Disease 0
. O 0

In O 0
the O 0
present O 0
study O 0
, O 0
we O 0
hypothesized O 0
that O 0
blocking O 0
EndoMT O 0
reduces O 0
the O 0
early O 0
development O 0
of O 0
diabetic B-Disease 0
nephropathy I-Disease 0
. O 0

RESEARCH O 0
DESIGN O 0
AND O 0
METHODS O 0
: O 0
EndoMT O 0
was O 0
induced O 0
in O 0
a O 0
mouse O 0
pancreatic O 0
microvascular O 0
endothelial O 0
cell O 0
line O 0
( O 0
MMEC O 0
) O 0
in O 0
the O 0
presence O 0
of O 0
advanced O 0
glycation O 0
end O 0
products O 0
( O 0
AGEs O 0
) O 0
and O 0
in O 0
the O 0
endothelial O 0
lineage O 0
- O 0
traceble O 0
mouse O 0
line O 0
Tie2 O 0
- O 0
Cre O 0
; O 0
Loxp O 0
- O 0
EGFP O 0
by O 0
administration O 0
of O 0
AGEs O 0
, O 0
with O 0
nonglycated O 0
mouse O 0
albumin O 0
serving O 0
as O 0
a O 0
control O 0
. O 0

Phosphorylated O 0
Smad3 O 0
was O 0
detected O 0
by O 0
immunoprecipitation O 0
/ O 0
Western O 0
blotting O 0
and O 0
confocal O 0
microscopy O 0
. O 0

Blocking O 0
studies O 0
using O 0
receptor O 0
for O 0
AGE O 0
siRNA O 0
and O 0
a O 0
specific O 0
inhibitor O 0
of O 0
Smad3 O 0
( O 0
SIS3 O 0
) O 0
were O 0
performed O 0
in O 0
MMECs O 0
and O 0
in O 0
STZ B-Chemical 0
- O 0
induced O 0
diabetic B-Disease 0
nephropathy I-Disease 0
in O 0
Tie2 O 0
- O 0
Cre O 0
; O 0
Loxp O 0
- O 0
EGFP O 0
mice O 0
. O 0

RESULTS O 0
: O 0
Confocal O 0
microscopy O 0
and O 0
real O 0
- O 0
time O 0
PCR O 0
demonstrated O 0
that O 0
AGEs O 0
induced O 0
EndoMT O 0
in O 0
MMECs O 0
and O 0
in O 0
Tie2 O 0
- O 0
Cre O 0
; O 0
Loxp O 0
- O 0
EGFP O 0
mice O 0
. O 0

Immunoprecipitation O 0
/ O 0
Western O 0
blotting O 0
showed O 0
that O 0
Smad3 O 0
was O 0
activated O 0
by O 0
AGEs O 0
but O 0
was O 0
inhibited O 0
by O 0
SIS3 O 0
in O 0
MMECs O 0
and O 0
in O 0
STZ B-Chemical 0
- O 0
induced O 0
diabetic B-Disease 0
nephropathy I-Disease 0
. O 0

Confocal O 0
microscopy O 0
and O 0
real O 0
- O 0
time O 0
PCR O 0
further O 0
demonstrated O 0
that O 0
SIS3 O 0
abrogated O 0
EndoMT O 0
, O 0
reduced O 0
renal O 0
fibrosis B-Disease 0
, O 0
and O 0
retarded O 0
progression O 0
of O 0
nephropathy B-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
EndoMT O 0
is O 0
a O 0
novel O 0
pathway O 0
leading O 0
to O 0
early O 0
development O 0
of O 0
diabetic B-Disease 0
nephropathy I-Disease 0
. O 0

Blockade O 0
of O 0
EndoMT O 0
by O 0
SIS3 O 0
may O 0
provide O 0
a O 0
new O 0
strategy O 0
to O 0
retard O 0
the O 0
progression O 0
of O 0
diabetic B-Disease 0
nephropathy I-Disease 0
and O 0
other O 0
diabetes B-Disease 0
complications I-Disease 0
. O 0

Cytostatic O 0
and O 0
anti O 0
- O 0
angiogenic O 0
effects O 0
of O 0
temsirolimus B-Chemical 0
in O 0
refractory O 0
mantle B-Disease 0
cell I-Disease 0
lymphoma I-Disease 0
. O 0

Mantle B-Disease 0
cell I-Disease 0
lymphoma I-Disease 0
( O 0
MCL B-Disease 0
) O 0
is O 0
a O 0
rare O 0
and O 0
aggressive O 0
type O 0
of O 0
B B-Disease 0
- I-Disease 0
cell I-Disease 0
non I-Disease 0
- I-Disease 0
Hodgkin I-Disease 0
' I-Disease 0
s I-Disease 0
lymphoma I-Disease 0
. O 0

Patients O 0
become O 0
progressively O 0
refractory O 0
to O 0
conventional O 0
chemotherapy O 0
, O 0
and O 0
their O 0
prognosis O 0
is O 0
poor O 0
. O 0

However O 0
, O 0
a O 0
38 O 0
% O 0
remission O 0
rate O 0
has O 0
been O 0
recently O 0
reported O 0
in O 0
refractory O 0
MCL B-Disease 0
treated O 0
with O 0
temsirolimus B-Chemical 0
, O 0
a O 0
mTOR O 0
inhibitor O 0
. O 0
Here O 0
we O 0
had O 0
the O 0
opportunity O 0
to O 0
study O 0
a O 0
case O 0
of O 0
refractory O 0
MCL B-Disease 0
who O 0
had O 0
tumor B-Disease 0
regression O 0
two O 0
months O 0
after O 0
temsirolimus B-Chemical 0
treatment O 0
, O 0
and O 0
a O 0
progression O 0
- O 0
free O 0
survival O 0
of O 0
10 O 0
months O 0
. O 0

In O 0
this O 0
case O 0
, O 0
lymph O 0
node O 0
biopsies O 0
were O 0
performed O 0
before O 0
and O 0
six O 0
months O 0
after O 0
temsirolimus B-Chemical 0
therapy O 0
. O 0

Comparison O 0
of O 0
the O 0
two O 0
biopsies O 0
showed O 0
that O 0
temsirolimus B-Chemical 0
inhibited O 0
tumor B-Disease 0
cell O 0
proliferation O 0
through O 0
cell O 0
cycle O 0
arrest O 0
, O 0
but O 0
did O 0
not O 0
induce O 0
any O 0
change O 0
in O 0
the O 0
number O 0
of O 0
apoptotic O 0
tumor B-Disease 0
cells O 0
. O 0

Apart O 0
from O 0
this O 0
cytostatic O 0
effect O 0
, O 0
temsirolimus B-Chemical 0
had O 0
an O 0
antiangiogenic O 0
effect O 0
with O 0
decrease O 0
of O 0
tumor B-Disease 0
microvessel O 0
density O 0
and O 0
of O 0
VEGF O 0
expression O 0
. O 0

Moreover O 0
, O 0
numerous O 0
patchy O 0
, O 0
well O 0
- O 0
limited O 0
fibrotic O 0
areas O 0
, O 0
compatible O 0
with O 0
post O 0
- O 0
necrotic B-Disease 0
tissue O 0
repair O 0
, O 0
were O 0
found O 0
after O 0
6 O 0
- O 0
month O 0
temsirolimus B-Chemical 0
therapy O 0
. O 0

Thus O 0
, O 0
temsirolimus B-Chemical 0
reduced O 0
tumor B-Disease 0
burden O 0
through O 0
associated O 0
cytostatic O 0
and O 0
anti O 0
- O 0
angiogenic O 0
effects O 0
. O 0
This O 0
dual O 0
effect O 0
of O 0
temsirolimus B-Chemical 0
on O 0
tumor B-Disease 0
tissue O 0
could O 0
contribute O 0
to O 0
its O 0
recently O 0
reported O 0
efficiency O 0
in O 0
refractory O 0
MCL B-Disease 0
resistant O 0
to O 0
conventional O 0
chemotherapy O 0
. O 0

Acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
due O 0
to O 0
rifampicin B-Chemical 0
. O 0

A O 0
23 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
patient O 0
with O 0
bacteriologically O 0
proven O 0
pulmonary B-Disease 0
tuberculosis I-Disease 0
was O 0
treated O 0
with O 0
the O 0
various O 0
regimens O 0
of O 0
antituberculosis O 0
drugs O 0
for O 0
nearly O 0
15 O 0
months O 0
. O 0

Rifampicin B-Chemical 0
was O 0
administered O 0
thrice O 0
as O 0
one O 0
of O 0
the O 0
3 O 0
- O 0
4 O 0
drug O 0
regimen O 0
and O 0
each O 0
time O 0
he O 0
developed O 0
untoward O 0
side O 0
effects O 0
like O 0
nausea B-Disease 0
, O 0
vomiting B-Disease 0
and O 0
fever B-Disease 0
with O 0
chills O 0
and O 0
rigors O 0
. O 0

The O 0
last O 0
such O 0
episode O 0
was O 0
of O 0
acute O 0
renal O 0
failure O 0
at O 0
which O 0
stage O 0
the O 0
patient O 0
was O 0
seen O 0
by O 0
the O 0
authors O 0
of O 0
this O 0
report O 0
. O 0

The O 0
patient O 0
, O 0
however O 0
, O 0
made O 0
a O 0
full O 0
recovery O 0
. O 0

Syncope B-Disease 0
caused O 0
by O 0
hyperkalemia B-Disease 0
during O 0
use O 0
of O 0
a O 0
combined O 0
therapy O 0
with O 0
the O 0
angiotensin B-Chemical 0
- O 0
converting O 0
enzyme O 0
inhibitor O 0
and O 0
spironolactone B-Chemical 0
. O 0

A O 0
76 O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
a O 0
history O 0
of O 0
coronary O 0
artery O 0
bypass O 0
grafting O 0
and O 0
prior O 0
myocardial B-Disease 0
infarction I-Disease 0
was O 0
transferred O 0
to O 0
the O 0
emergency O 0
room O 0
with O 0
loss B-Disease 0
of I-Disease 0
consciousness I-Disease 0
due O 0
to O 0
marked O 0
bradycardia B-Disease 0
caused O 0
by O 0
hyperkalemia B-Disease 0
. O 0

The O 0
concentration O 0
of O 0
serum O 0
potassium B-Chemical 0
was O 0
high O 0
, O 0
and O 0
normal O 0
sinus O 0
rhythm O 0
was O 0
restored O 0
after O 0
correction O 0
of O 0
the O 0
serum O 0
potassium B-Chemical 0
level O 0
. O 0

The O 0
cause O 0
of O 0
hyperkalemia B-Disease 0
was O 0
considered O 0
to O 0
be O 0
several O 0
doses O 0
of O 0
spiranolactone B-Chemical 0
, O 0
an O 0
aldosterone B-Chemical 0
antagonist O 0
, O 0
in O 0
addition O 0
to O 0
the O 0
long O 0
- O 0
term O 0
intake O 0
of O 0
ramipril B-Chemical 0
, O 0
an O 0
ACE O 0
inhibitor O 0
. O 0

This O 0
case O 0
is O 0
a O 0
good O 0
example O 0
of O 0
electrolyte O 0
imbalance O 0
causing O 0
acute O 0
life O 0
- O 0
threatening O 0
cardiac O 0
events O 0
. O 0

Clinicians O 0
should O 0
be O 0
alert O 0
to O 0
the O 0
possibility O 0
of O 0
hyperkalemia B-Disease 0
, O 0
especially O 0
in O 0
elderly O 0
patients O 0
using O 0
ACE O 0
/ O 0
ARB O 0
in O 0
combination O 0
with O 0
potassium B-Chemical 0
sparing O 0
agents O 0
and O 0
who O 0
have O 0
mild O 0
renal B-Disease 0
disturbance I-Disease 0
. O 0

Diffuse O 0
skeletal O 0
pain B-Disease 0
after O 0
administration O 0
of O 0
alendronate B-Chemical 0
. O 0

BACKGROUND O 0
: O 0
Osteoporosis B-Disease 0
is O 0
caused O 0
by O 0
bone O 0
resorption O 0
in O 0
excess O 0
of O 0
bone O 0
formation O 0
, O 0
and O 0
bisphosphonates B-Chemical 0
, O 0
are O 0
used O 0
to O 0
inhibit O 0
bone O 0
resorption O 0
. O 0

Alendronate B-Chemical 0
, O 0
a O 0
biphosphonate B-Chemical 0
, O 0
is O 0
effective O 0
for O 0
both O 0
the O 0
treatment O 0
and O 0
prevention O 0
of O 0
osteoporosis B-Disease 0
in O 0
postmenopausal O 0
women O 0
. O 0

Side O 0
effects O 0
are O 0
relatively O 0
few O 0
and O 0
prominently O 0
gastrointestinal O 0
. O 0

Musculoskeletal B-Disease 0
pain I-Disease 0
may O 0
be O 0
an O 0
important O 0
side O 0
effect O 0
in O 0
these O 0
patients O 0
. O 0

We O 0
presented O 0
a O 0
patient O 0
admitted O 0
to O 0
our O 0
out O 0
- O 0
patient O 0
clinic O 0
with O 0
diffuse O 0
skeletal O 0
pain B-Disease 0
after O 0
three O 0
consecutive O 0
administration O 0
of O 0
alendronate B-Chemical 0
. O 0

CONCLUSION O 0
: O 0
We O 0
conclude O 0
that O 0
patients O 0
with O 0
osteoporosis B-Disease 0
can O 0
report O 0
pain B-Disease 0
, O 0
and O 0
bisphosphonate B-Chemical 0
- O 0
related O 0
pain B-Disease 0
should O 0
also O 0
be O 0
considered O 0
before O 0
ascribing O 0
this O 0
complaint O 0
to O 0
osteoporosis B-Disease 0
. O 0

Cerebrospinal O 0
fluid O 0
penetration O 0
of O 0
high O 0
- O 0
dose O 0
daptomycin B-Chemical 0
in O 0
suspected O 0
Staphylococcus O 0
aureus O 0
meningitis B-Disease 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
report O 0
a O 0
case O 0
of O 0
methicillin B-Chemical 0
- O 0
sensitive O 0
Staphylococcus O 0
aureus O 0
( O 0
MSSA O 0
) O 0
bacteremia B-Disease 0
with O 0
suspected O 0
MSSA O 0
meningitis B-Disease 0
treated O 0
with O 0
high O 0
- O 0
dose O 0
daptomycin B-Chemical 0
assessed O 0
with O 0
concurrent O 0
serum O 0
and O 0
cerebrospinal O 0
fluid O 0
( O 0
CSF O 0
) O 0
concentrations O 0
. O 0

CASE O 0
SUMMARY O 0
: O 0
A O 0
54 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
presented O 0
to O 0
the O 0
emergency O 0
department O 0
with O 0
generalized O 0
weakness B-Disease 0
and O 0
presumed O 0
health O 0
- O 0
care O 0
- O 0
associated O 0
pneumonia B-Disease 0
shown O 0
on O 0
chest O 0
radiograph O 0
. O 0

Treatment O 0
was O 0
empirically O 0
initiated O 0
with O 0
vancomycin B-Chemical 0
, O 0
levofloxacin B-Chemical 0
, O 0
and O 0
piperacillin B-Chemical 0
/ O 0
tazobactam B-Chemical 0
. O 0

Blood O 0
cultures O 0
revealed O 0
S O 0
. O 0
aureus O 0
susceptible O 0
to O 0
oxacillin B-Chemical 0
. O 0

Empiric O 0
antibiotic O 0
treatment O 0
was O 0
narrowed O 0
to O 0
nafcillin B-Chemical 0
on O 0
day O 0
4 O 0
. O 0

On O 0
day O 0
8 O 0
, O 0
the O 0
patient O 0
developed O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
( O 0
serum O 0
creatinine B-Chemical 0
1 O 0
. O 0
9 O 0
mg O 0
/ O 0
dL O 0
, O 0
increased O 0
from O 0
1 O 0
. O 0
2 O 0
mg O 0
/ O 0
dL O 0
the O 0
previous O 0
day O 0
and O 0
0 O 0
. O 0
8 O 0
mg O 0
/ O 0
dL O 0
on O 0
admission O 0
) O 0
. O 0

The O 0
patient O 0
' O 0
s O 0
Glasgow O 0
Coma O 0
Score O 0
was O 0
3 O 0
, O 0
with O 0
normal O 0
findings O 0
shown O 0
on O 0
computed O 0
tomography O 0
scan O 0
of O 0
the O 0
head O 0
72 O 0
hours O 0
following O 0
an O 0
episode O 0
of O 0
cardiac B-Disease 0
arrest I-Disease 0
on O 0
day O 0
10 O 0
. O 0

The O 0
patient O 0
experienced O 0
relapsing O 0
MSSA O 0
bacteremia B-Disease 0
on O 0
day O 0
9 O 0
, O 0
increasing O 0
the O 0
suspicion O 0
for O 0
a O 0
central O 0
nervous O 0
system O 0
( O 0
CNS O 0
) O 0
infection B-Disease 0
. O 0

Nafcillin B-Chemical 0
was O 0
discontinued O 0
and O 0
daptomycin B-Chemical 0
9 O 0
mg O 0
/ O 0
kg O 0
daily O 0
was O 0
initiated O 0
for O 0
suspected O 0
meningitis B-Disease 0
and O 0
was O 0
continued O 0
until O 0
the O 0
patient O 0
' O 0
s O 0
death O 0
on O 0
day O 0
16 O 0
. O 0

Daptomycin B-Chemical 0
serum O 0
and O 0
CSF O 0
trough O 0
concentrations O 0
were O 0
11 O 0
. O 0
21 O 0
ug O 0
/ O 0
mL O 0
and O 0
0 O 0
. O 0
52 O 0
ug O 0
/ O 0
mL O 0
, O 0
respectively O 0
, O 0
prior O 0
to O 0
the O 0
third O 0
dose O 0
. O 0

Lumbar O 0
puncture O 0
results O 0
were O 0
inconclusive O 0
and O 0
no O 0
further O 0
blood O 0
cultures O 0
were O 0
positive O 0
for O 0
MSSA O 0
. O 0

Creatine B-Chemical 0
kinase O 0
levels O 0
were O 0
normal O 0
prior O 0
to O 0
daptomycin B-Chemical 0
therapy O 0
and O 0
were O 0
not O 0
reassessed O 0
. O 0

DISCUSSION O 0
: O 0
Daptomycin B-Chemical 0
was O 0
initiated O 0
in O 0
our O 0
patient O 0
secondary O 0
to O 0
possible O 0
nafcillin B-Chemical 0
- O 0
induced O 0
acute O 0
interstitial B-Disease 0
nephritis I-Disease 0
and O 0
relapsing O 0
bacteremia B-Disease 0
. O 0

At O 0
a O 0
dose O 0
of O 0
9 O 0
mg O 0
/ O 0
kg O 0
, O 0
resultant O 0
penetration O 0
of O 0
5 O 0
% O 0
was O 0
higher O 0
than O 0
in O 0
previous O 0
reports O 0
, O 0
more O 0
consistent O 0
with O 0
inflamed O 0
meninges O 0
. O 0

CONCLUSIONS O 0
: O 0
High O 0
- O 0
dose O 0
daptomycin B-Chemical 0
may O 0
be O 0
an O 0
alternative O 0
option O 0
for O 0
MSSA O 0
bacteremia B-Disease 0
with O 0
or O 0
without O 0
a O 0
CNS O 0
source O 0
in O 0
patients O 0
who O 0
have O 0
failed O 0
or O 0
cannot O 0
tolerate O 0
standard O 0
therapy O 0
. O 0

Further O 0
clinical O 0
evaluation O 0
in O 0
patients O 0
with O 0
confirmed O 0
meningitis B-Disease 0
is O 0
warranted O 0
. O 0

The O 0
role O 0
of O 0
nitric B-Chemical 0
oxide I-Chemical 0
in O 0
convulsions B-Disease 0
induced O 0
by O 0
lindane B-Chemical 0
in O 0
rats O 0
. O 0

Lindane B-Chemical 0
is O 0
an O 0
organochloride O 0
pesticide O 0
and O 0
scabicide O 0
. O 0

It O 0
evokes O 0
convulsions B-Disease 0
mainly O 0
trough O 0
the O 0
blockage O 0
of O 0
GABA B-Chemical 0
( O 0
A O 0
) O 0
receptors O 0
. O 0

Nitric B-Chemical 0
oxide I-Chemical 0
( O 0
NO B-Chemical 0
) O 0
, O 0
gaseous O 0
neurotransmitter O 0
, O 0
has O 0
contradictor O 0
role O 0
in O 0
epileptogenesis O 0
due O 0
to O 0
opposite O 0
effects O 0
of O 0
L B-Chemical 0
- I-Chemical 0
arginine I-Chemical 0
, O 0
precursor O 0
of O 0
NO B-Chemical 0
syntheses O 0
( O 0
NOS O 0
) O 0
, O 0
and O 0
L B-Chemical 0
- I-Chemical 0
NAME I-Chemical 0
( O 0
NOS O 0
inhibitor O 0
) O 0
observed O 0
in O 0
different O 0
epilepsy B-Disease 0
models O 0
. O 0

The O 0
aim O 0
of O 0
the O 0
current O 0
study O 0
was O 0
to O 0
determine O 0
the O 0
effects O 0
of O 0
NO B-Chemical 0
on O 0
the O 0
behavioral O 0
and O 0
EEG O 0
characteristics O 0
of O 0
lindane B-Chemical 0
- O 0
induced O 0
epilepsy B-Disease 0
in O 0
male O 0
Wistar O 0
albino O 0
rats O 0
. O 0

The O 0
administration O 0
of O 0
L B-Chemical 0
- I-Chemical 0
arginine I-Chemical 0
( O 0
600 O 0
, O 0
800 O 0
and O 0
1000 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
in O 0
dose O 0
- O 0
dependent O 0
manner O 0
significantly O 0
increased O 0
convulsion B-Disease 0
incidence O 0
and O 0
severity O 0
and O 0
shortened O 0
latency O 0
time O 0
to O 0
first O 0
convulsion B-Disease 0
elicited O 0
by O 0
lower O 0
lindane B-Chemical 0
dose O 0
( O 0
4 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

On O 0
the O 0
contrary O 0
, O 0
pretreatment O 0
with O 0
L B-Chemical 0
- I-Chemical 0
NAME I-Chemical 0
( O 0
500 O 0
, O 0
700 O 0
and O 0
900 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
decreased O 0
convulsion B-Disease 0
incidence O 0
and O 0
severity O 0
and O 0
prolonged O 0
latency O 0
time O 0
to O 0
convulsion B-Disease 0
following O 0
injection O 0
with O 0
a O 0
convulsive B-Disease 0
dose O 0
of O 0
lindane B-Chemical 0
( O 0
8 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

EEG O 0
analyses O 0
showed O 0
increase O 0
of O 0
number O 0
and O 0
duration O 0
of O 0
ictal O 0
periods O 0
in O 0
EEG O 0
of O 0
rats O 0
receiving O 0
l B-Chemical 0
- I-Chemical 0
arginine I-Chemical 0
prior O 0
to O 0
lindane B-Chemical 0
and O 0
decrease O 0
of O 0
this O 0
number O 0
in O 0
rats O 0
pretreated O 0
with O 0
L B-Chemical 0
- I-Chemical 0
NAME I-Chemical 0
. O 0

These O 0
results O 0
support O 0
the O 0
conclusion O 0
that O 0
NO B-Chemical 0
plays O 0
a O 0
role O 0
of O 0
endogenous O 0
convulsant O 0
in O 0
rat O 0
model O 0
of O 0
lindane B-Chemical 0
seizures B-Disease 0
. O 0

Severe O 0
polyneuropathy B-Disease 0
and O 0
motor O 0
loss O 0
after O 0
intrathecal O 0
thiotepa B-Chemical 0
combination O 0
chemotherapy O 0
: O 0
description O 0
of O 0
two O 0
cases O 0
. O 0

Two O 0
cases O 0
of O 0
severe O 0
delayed O 0
neurologic B-Disease 0
toxicity I-Disease 0
related O 0
to O 0
the O 0
administration O 0
of O 0
intrathecal O 0
( O 0
IT O 0
) O 0
combination O 0
chemotherapy O 0
including O 0
thiotepa B-Chemical 0
( O 0
TSPA B-Chemical 0
) O 0
are O 0
presented O 0
. O 0

Both O 0
cases O 0
developed O 0
axonal B-Disease 0
neuropathy I-Disease 0
with O 0
motor O 0
predominance O 0
in O 0
the O 0
lower O 0
extremities O 0
1 O 0
and O 0
6 O 0
months O 0
after O 0
IT O 0
chemotherapy O 0
was O 0
administered O 0
. O 0

Neurologic B-Disease 0
toxicities I-Disease 0
have O 0
been O 0
described O 0
with O 0
IT O 0
- O 0
methotrexate B-Chemical 0
, O 0
IT O 0
- O 0
cytosine B-Chemical 0
arabinoside I-Chemical 0
and O 0
IT O 0
- O 0
TSPA B-Chemical 0
. O 0

To O 0
our O 0
knowledge O 0
, O 0
however O 0
, O 0
axonal B-Disease 0
neuropathy I-Disease 0
following O 0
administration O 0
of O 0
these O 0
three O 0
agents O 0
has O 0
not O 0
been O 0
previously O 0
described O 0
. O 0

In O 0
spite O 0
of O 0
the O 0
fact O 0
that O 0
TSPA B-Chemical 0
is O 0
a O 0
useful O 0
IT O 0
agent O 0
, O 0
its O 0
combination O 0
with O 0
MTX B-Chemical 0
, O 0
ara B-Chemical 0
- I-Chemical 0
C I-Chemical 0
and O 0
radiotherapy O 0
could O 0
cause O 0
severe O 0
neurotoxicity B-Disease 0
. O 0

This O 0
unexpected O 0
complication O 0
indicates O 0
the O 0
need O 0
for O 0
further O 0
toxicology O 0
research O 0
on O 0
IT O 0
- O 0
TSPA B-Chemical 0
. O 0

Effects O 0
of O 0
cromakalim B-Chemical 0
and O 0
pinacidil B-Chemical 0
on O 0
large O 0
epicardial O 0
and O 0
small O 0
coronary O 0
arteries O 0
in O 0
conscious O 0
dogs O 0
. O 0

The O 0
effects O 0
of O 0
i O 0
. O 0
v O 0
. O 0
bolus O 0
administration O 0
of O 0
cromakalim B-Chemical 0
( O 0
1 O 0
- O 0
10 O 0
micrograms O 0
/ O 0
kg O 0
) O 0
and O 0
pinacidil B-Chemical 0
( O 0
3 O 0
- O 0
100 O 0
micrograms O 0
/ O 0
kg O 0
) O 0
on O 0
large O 0
( O 0
circumflex O 0
artery O 0
) O 0
and O 0
small O 0
coronary O 0
arteries O 0
and O 0
on O 0
systemic O 0
hemodynamics O 0
were O 0
investigated O 0
in O 0
chronically O 0
instrumented O 0
conscious O 0
dogs O 0
and O 0
compared O 0
to O 0
those O 0
of O 0
nitroglycerin B-Chemical 0
( O 0
0 O 0
. O 0
03 O 0
- O 0
10 O 0
micrograms O 0
/ O 0
kg O 0
) O 0
. O 0

Nitroglycerin B-Chemical 0
, O 0
up O 0
to O 0
0 O 0
. O 0
3 O 0
micrograms O 0
/ O 0
kg O 0
, O 0
selectively O 0
increased O 0
circumflex O 0
artery O 0
diameter O 0
( O 0
CxAD O 0
) O 0
without O 0
simultaneously O 0
affecting O 0
any O 0
other O 0
cardiac O 0
or O 0
systemic O 0
hemodynamic O 0
parameter O 0
. O 0

In O 0
contrast O 0
, O 0
cromakalim B-Chemical 0
and O 0
pinacidil B-Chemical 0
at O 0
all O 0
doses O 0
and O 0
nitroglycerin B-Chemical 0
at O 0
doses O 0
higher O 0
than O 0
0 O 0
. O 0
3 O 0
micrograms O 0
/ O 0
kg O 0
simultaneously O 0
and O 0
dose O 0
- O 0
dependently O 0
increased O 0
CxAD O 0
, O 0
coronary O 0
blood O 0
flow O 0
and O 0
heart O 0
rate O 0
and O 0
decreased O 0
coronary O 0
vascular O 0
resistance O 0
and O 0
aortic O 0
pressure O 0
. O 0

Cromakalim B-Chemical 0
was O 0
approximately O 0
8 O 0
- O 0
to O 0
9 O 0
. O 0
5 O 0
- O 0
fold O 0
more O 0
potent O 0
than O 0
pinacidil B-Chemical 0
in O 0
increasing O 0
CxAD O 0
. O 0

Vasodilation O 0
of O 0
large O 0
and O 0
small O 0
coronary O 0
vessels O 0
and O 0
hypotension B-Disease 0
induced O 0
by O 0
cromakalim B-Chemical 0
and O 0
pinacidil B-Chemical 0
were O 0
not O 0
affected O 0
by O 0
prior O 0
combined O 0
beta B-Chemical 0
adrenergic I-Chemical 0
and I-Chemical 0
muscarinic I-Chemical 0
receptors I-Chemical 0
blockade I-Chemical 0
but O 0
drug O 0
- O 0
induced O 0
tachycardia B-Disease 0
was O 0
abolished O 0
. O 0

When O 0
circumflex O 0
artery O 0
blood O 0
flow O 0
was O 0
maintained O 0
constant O 0
, O 0
the O 0
increases O 0
in O 0
CxAD O 0
induced O 0
by O 0
cromakalim B-Chemical 0
( O 0
10 O 0
micrograms O 0
/ O 0
kg O 0
) O 0
, O 0
pinacidil B-Chemical 0
( O 0
30 O 0
micrograms O 0
/ O 0
kg O 0
) O 0
and O 0
nitroglycerin B-Chemical 0
( O 0
10 O 0
micrograms O 0
/ O 0
kg O 0
) O 0
were O 0
reduced O 0
by O 0
68 O 0
+ O 0
/ O 0
- O 0
7 O 0
, O 0
54 O 0
+ O 0
/ O 0
- O 0
9 O 0
and O 0
1 O 0
+ O 0
/ O 0
- O 0
1 O 0
% O 0
, O 0
respectively O 0
. O 0

Thus O 0
, O 0
whereas O 0
nitroglycerin B-Chemical 0
preferentially O 0
and O 0
flow O 0
- O 0
independently O 0
dilates O 0
large O 0
coronary O 0
arteries O 0
, O 0
cromakalim B-Chemical 0
and O 0
pinacidil B-Chemical 0
dilate O 0
both O 0
large O 0
and O 0
small O 0
coronary O 0
arteries O 0
and O 0
this O 0
effect O 0
is O 0
not O 0
dependent O 0
upon O 0
the O 0
simultaneous O 0
beta O 0
adrenoceptors O 0
- O 0
mediated O 0
rise O 0
in O 0
myocardial O 0
metabolic O 0
demand O 0
. O 0

Finally O 0
, O 0
two O 0
mechanisms O 0
at O 0
least O 0
, O 0
direct O 0
vasodilation O 0
and O 0
flow O 0
dependency O 0
, O 0
are O 0
involved O 0
in O 0
the O 0
cromakalim B-Chemical 0
- O 0
and O 0
pinacidil B-Chemical 0
- O 0
induced O 0
increase O 0
in O 0
CxAD O 0
. O 0

Mefenamic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
neutropenia B-Disease 0
and O 0
renal B-Disease 0
failure I-Disease 0
in O 0
elderly O 0
females O 0
with O 0
hypothyroidism B-Disease 0
. O 0

We O 0
report O 0
mefenamic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
non O 0
- O 0
oliguric O 0
renal B-Disease 0
failure I-Disease 0
and O 0
severe O 0
neutropenia B-Disease 0
occurring O 0
simultaneously O 0
in O 0
two O 0
elderly O 0
females O 0
. O 0

The O 0
neutropenia B-Disease 0
was O 0
due O 0
to O 0
maturation O 0
arrest O 0
of O 0
the O 0
myeloid O 0
series O 0
in O 0
one O 0
patient O 0
. O 0

Both O 0
patients O 0
were O 0
also O 0
hypothyroid B-Disease 0
, O 0
but O 0
it O 0
is O 0
not O 0
clear O 0
whether O 0
this O 0
was O 0
a O 0
predisposing O 0
factor O 0
to O 0
the O 0
development O 0
of O 0
these O 0
adverse O 0
reactions O 0
. O 0

However O 0
, O 0
it O 0
would O 0
seem O 0
prudent O 0
not O 0
to O 0
use O 0
mefenamic B-Chemical 0
acid I-Chemical 0
in O 0
hypothyroid B-Disease 0
patients O 0
until O 0
the O 0
hypothyroidism B-Disease 0
has O 0
been O 0
corrected O 0
. O 0

Etiology O 0
of O 0
hypercalcemia B-Disease 0
in O 0
hemodialysis O 0
patients O 0
on O 0
calcium B-Chemical 0
carbonate I-Chemical 0
therapy O 0
. O 0

Fourteen O 0
of O 0
39 O 0
dialysis O 0
patients O 0
( O 0
36 O 0
% O 0
) O 0
became O 0
hypercalcemic B-Disease 0
after O 0
switching O 0
to O 0
calcium B-Chemical 0
carbonate I-Chemical 0
as O 0
their O 0
principal O 0
phosphate B-Chemical 0
binder O 0
. O 0

In O 0
order O 0
to O 0
identify O 0
risk O 0
factors O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
hypercalcemia B-Disease 0
, O 0
indirect O 0
parameters O 0
of O 0
intestinal O 0
calcium B-Chemical 0
reabsorption O 0
and O 0
bone O 0
turnover O 0
rate O 0
in O 0
these O 0
14 O 0
patients O 0
were O 0
compared O 0
with O 0
results O 0
in O 0
14 O 0
eucalcemic O 0
patients O 0
matched O 0
for O 0
age O 0
, O 0
sex O 0
, O 0
length O 0
of O 0
time O 0
on O 0
dialysis O 0
, O 0
and O 0
etiology O 0
of O 0
renal B-Disease 0
disease I-Disease 0
. O 0

In O 0
addition O 0
to O 0
experiencing O 0
hypercalcemic B-Disease 0
episodes O 0
with O 0
peak O 0
calcium B-Chemical 0
values O 0
of O 0
2 O 0
. O 0
7 O 0
to O 0
3 O 0
. O 0
8 O 0
mmol O 0
/ O 0
L O 0
( O 0
10 O 0
. O 0
7 O 0
to O 0
15 O 0
. O 0
0 O 0
mg O 0
/ O 0
dL O 0
) O 0
, O 0
patients O 0
in O 0
the O 0
hypercalcemic B-Disease 0
group O 0
exhibited O 0
a O 0
significant O 0
increase O 0
in O 0
the O 0
mean O 0
calcium B-Chemical 0
concentration O 0
obtained O 0
during O 0
6 O 0
months O 0
before O 0
the O 0
switch O 0
, O 0
compared O 0
with O 0
the O 0
mean O 0
value O 0
obtained O 0
during O 0
the O 0
7 O 0
months O 0
of O 0
observation O 0
after O 0
the O 0
switch O 0
( O 0
2 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
03 O 0
to O 0
2 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
03 O 0
mmol O 0
/ O 0
L O 0
[ O 0
9 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
to O 0
10 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
mg O 0
/ O 0
dL O 0
] O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
006 O 0
) O 0
. O 0

In O 0
contrast O 0
, O 0
eucalcemic O 0
patients O 0
exhibited O 0
no O 0
change O 0
in O 0
mean O 0
calcium B-Chemical 0
values O 0
over O 0
the O 0
same O 0
time O 0
period O 0
( O 0
2 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
05 O 0
to O 0
2 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
05 O 0
mmol O 0
/ O 0
L O 0
[ O 0
9 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
to O 0
9 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
mg O 0
/ O 0
dL O 0
] O 0
) O 0
. O 0

CaCO3 B-Chemical 0
dosage O 0
, O 0
calculated O 0
dietary O 0
calcium B-Chemical 0
intake O 0
, O 0
and O 0
circulating O 0
levels O 0
of O 0
vitamin B-Chemical 0
D I-Chemical 0
metabolites O 0
were O 0
similar O 0
in O 0
both O 0
groups O 0
. O 0

Physical O 0
activity O 0
index O 0
and O 0
predialysis O 0
serum O 0
bicarbonate B-Chemical 0
levels O 0
also O 0
were O 0
similar O 0
in O 0
both O 0
groups O 0
. O 0

However O 0
, O 0
there O 0
was O 0
a O 0
significant O 0
difference O 0
in O 0
parameters O 0
reflecting O 0
bone O 0
turnover O 0
rates O 0
between O 0
groups O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Late O 0
- O 0
onset O 0
scleroderma B-Disease 0
renal I-Disease 0
crisis I-Disease 0
induced O 0
by O 0
tacrolimus B-Chemical 0
and O 0
prednisolone B-Chemical 0
: O 0
a O 0
case O 0
report O 0
. O 0

Scleroderma B-Disease 0
renal I-Disease 0
crisis I-Disease 0
( O 0
SRC B-Disease 0
) O 0
is O 0
a O 0
rare O 0
complication O 0
of O 0
systemic B-Disease 0
sclerosis I-Disease 0
( O 0
SSc B-Disease 0
) O 0
but O 0
can O 0
be O 0
severe O 0
enough O 0
to O 0
require O 0
temporary O 0
or O 0
permanent O 0
renal O 0
replacement O 0
therapy O 0
. O 0

Moderate O 0
to O 0
high O 0
dose O 0
corticosteroid B-Chemical 0
use O 0
is O 0
recognized O 0
as O 0
a O 0
major O 0
risk O 0
factor O 0
for O 0
SRC B-Disease 0
. O 0

Furthermore O 0
, O 0
there O 0
have O 0
been O 0
reports O 0
of O 0
thrombotic B-Disease 0
microangiopathy I-Disease 0
precipitated O 0
by O 0
cyclosporine B-Chemical 0
in O 0
patients O 0
with O 0
SSc B-Disease 0
. O 0

In O 0
this O 0
article O 0
, O 0
we O 0
report O 0
a O 0
patient O 0
with O 0
SRC B-Disease 0
induced O 0
by O 0
tacrolimus B-Chemical 0
and O 0
corticosteroids B-Chemical 0
. O 0

The O 0
aim O 0
of O 0
this O 0
work O 0
is O 0
to O 0
call O 0
attention O 0
to O 0
the O 0
risk O 0
of O 0
tacrolimus B-Chemical 0
use O 0
in O 0
patients O 0
with O 0
SSc B-Disease 0
. O 0

Methyldopa B-Chemical 0
- O 0
induced O 0
hemolytic B-Disease 0
anemia I-Disease 0
in O 0
a O 0
15 O 0
year O 0
old O 0
presenting O 0
as O 0
near O 0
- O 0
syncope B-Disease 0
. O 0

Methyldopa B-Chemical 0
is O 0
an O 0
antihypertensive O 0
medication O 0
which O 0
is O 0
available O 0
generically O 0
and O 0
under O 0
the O 0
trade O 0
name O 0
Aldomet B-Chemical 0
that O 0
is O 0
widely O 0
prescribed O 0
in O 0
the O 0
adult O 0
population O 0
and O 0
infrequently O 0
used O 0
in O 0
children O 0
. O 0

Methyldopa B-Chemical 0
causes O 0
an O 0
autoimmune B-Disease 0
hemolytic I-Disease 0
anemia I-Disease 0
in O 0
a O 0
small O 0
percentage O 0
of O 0
patients O 0
who O 0
take O 0
the O 0
drug O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
methyldopa B-Chemical 0
- O 0
induced O 0
hemolytic B-Disease 0
anemia I-Disease 0
in O 0
a O 0
15 O 0
- O 0
year O 0
- O 0
old O 0
boy O 0
who O 0
presented O 0
to O 0
the O 0
emergency B-Disease 0
department I-Disease 0
with O 0
near O 0
- O 0
syncope B-Disease 0
. O 0

The O 0
boy O 0
had O 0
been O 0
treated O 0
with O 0
intravenous O 0
methyldopa B-Chemical 0
during O 0
a O 0
trauma B-Disease 0
admission O 0
seven O 0
weeks O 0
prior O 0
to O 0
presentation O 0
. O 0

Evaluation O 0
revealed O 0
a O 0
hemoglobin O 0
of O 0
three O 0
grams O 0
, O 0
3 O 0
+ O 0
Coombs O 0
' O 0
test O 0
with O 0
polyspecific O 0
anti O 0
- O 0
human O 0
globulin O 0
and O 0
monospecific O 0
IgG O 0
reagents O 0
, O 0
and O 0
a O 0
warm O 0
reacting O 0
autoantibody O 0
. O 0

Transfusion O 0
and O 0
corticosteroid B-Chemical 0
therapy O 0
resulted O 0
in O 0
a O 0
complete O 0
recovery O 0
of O 0
the O 0
patient O 0
. O 0

Emergency O 0
physicians O 0
treating O 0
children O 0
must O 0
be O 0
aware O 0
of O 0
this O 0
syndrome O 0
in O 0
order O 0
to O 0
diagnose O 0
and O 0
treat O 0
it O 0
correctly O 0
. O 0

A O 0
brief O 0
review O 0
of O 0
autoimmune O 0
and O 0
drug O 0
- O 0
induced O 0
hemolytic B-Disease 0
anemias I-Disease 0
is O 0
provided O 0
. O 0

The O 0
risk O 0
and O 0
associated O 0
factors O 0
of O 0
methamphetamine B-Chemical 0
psychosis B-Disease 0
in O 0
methamphetamine B-Chemical 0
- O 0
dependent O 0
patients O 0
in O 0
Malaysia O 0
. O 0

OBJECTIVE O 0
: O 0
The O 0
objective O 0
of O 0
this O 0
study O 0
was O 0
to O 0
determine O 0
the O 0
risk O 0
of O 0
lifetime O 0
and O 0
current O 0
methamphetamine B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
in O 0
patients O 0
with O 0
methamphetamine B-Chemical 0
dependence O 0
. O 0

The O 0
association O 0
between O 0
psychiatric O 0
co O 0
- O 0
morbidity O 0
and O 0
methamphetamine B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
was O 0
also O 0
studied O 0
. O 0

METHODS O 0
: O 0
This O 0
was O 0
a O 0
cross O 0
- O 0
sectional O 0
study O 0
conducted O 0
concurrently O 0
at O 0
a O 0
teaching O 0
hospital O 0
and O 0
a O 0
drug O 0
rehabilitation O 0
center O 0
in O 0
Malaysia O 0
. O 0

Patients O 0
with O 0
the O 0
diagnosis O 0
of O 0
methamphetamine B-Chemical 0
based O 0
on O 0
DSM O 0
- O 0
IV O 0
were O 0
interviewed O 0
using O 0
the O 0
Mini O 0
International O 0
Neuropsychiatric O 0
Interview O 0
( O 0
M O 0
. O 0
I O 0
. O 0
N O 0
. O 0
I O 0
. O 0
) O 0
for O 0
methamphetamine B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
and O 0
other O 0
Axis O 0
I O 0
psychiatric B-Disease 0
disorders I-Disease 0
. O 0

The O 0
information O 0
on O 0
sociodemographic O 0
background O 0
and O 0
drug O 0
use O 0
history O 0
was O 0
obtained O 0
from O 0
interview O 0
or O 0
medical O 0
records O 0
. O 0

RESULTS O 0
: O 0
Of O 0
292 O 0
subjects O 0
, O 0
47 O 0
. O 0
9 O 0
% O 0
of O 0
the O 0
subjects O 0
had O 0
a O 0
past O 0
history O 0
of O 0
psychotic B-Disease 0
symptoms I-Disease 0
and O 0
13 O 0
. O 0
0 O 0
% O 0
of O 0
the O 0
patients O 0
were O 0
having O 0
current O 0
psychotic B-Disease 0
symptoms I-Disease 0
. O 0

Co O 0
- O 0
morbid O 0
major O 0
depressive B-Disease 0
disorder I-Disease 0
( O 0
OR O 0
= O 0
7 O 0
. O 0
18 O 0
, O 0
95 O 0
CI O 0
= O 0
2 O 0
. O 0
612 O 0
- O 0
19 O 0
. O 0
708 O 0
) O 0
, O 0
bipolar B-Disease 0
disorder I-Disease 0
( O 0
OR O 0
= O 0
13 O 0
. O 0
807 O 0
, O 0
95 O 0
CI O 0
= O 0
5 O 0
. O 0
194 O 0
- O 0
36 O 0
. O 0
706 O 0
) O 0
, O 0
antisocial B-Disease 0
personality I-Disease 0
disorder I-Disease 0
( O 0
OR O 0
= O 0
12 O 0
. O 0
619 O 0
, O 0
95 O 0
CI O 0
= O 0
6 O 0
. O 0
702 O 0
- O 0
23 O 0
. O 0
759 O 0
) O 0
and O 0
heavy O 0
methamphetamine B-Chemical 0
uses O 0
were O 0
significantly O 0
associated O 0
with O 0
lifetime O 0
methamphetamine B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
after O 0
adjusted O 0
for O 0
other O 0
factors O 0
. O 0

Major B-Disease 0
depressive I-Disease 0
disorder I-Disease 0
( O 0
OR O 0
= O 0
2 O 0
. O 0
870 O 0
, O 0
CI O 0
= O 0
1 O 0
. O 0
154 O 0
- O 0
7 O 0
. O 0
142 O 0
) O 0
and O 0
antisocial B-Disease 0
personality I-Disease 0
disorder I-Disease 0
( O 0
OR O 0
= O 0
3 O 0
. O 0
299 O 0
, O 0
95 O 0
CI O 0
= O 0
1 O 0
. O 0
375 O 0
- O 0
7 O 0
. O 0
914 O 0
) O 0
were O 0
the O 0
only O 0
factors O 0
associated O 0
with O 0
current O 0
psychosis B-Disease 0
. O 0

CONCLUSION O 0
: O 0
There O 0
was O 0
a O 0
high O 0
risk O 0
of O 0
psychosis B-Disease 0
in O 0
patients O 0
with O 0
methamphetamine B-Chemical 0
dependence O 0
. O 0

It O 0
was O 0
associated O 0
with O 0
co O 0
- O 0
morbid O 0
affective B-Disease 0
disorder I-Disease 0
, O 0
antisocial B-Disease 0
personality I-Disease 0
, O 0
and O 0
heavy O 0
methamphetamine B-Chemical 0
use O 0
. O 0

It O 0
is O 0
recommended O 0
that O 0
all O 0
cases O 0
of O 0
methamphetamine B-Chemical 0
dependence O 0
should O 0
be O 0
screened O 0
for O 0
psychotic B-Disease 0
symptoms I-Disease 0
. O 0

Cerebellar O 0
sensory O 0
processing O 0
alterations O 0
impact O 0
motor O 0
cortical O 0
plasticity O 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
: O 0
clues O 0
from O 0
dyskinetic B-Disease 0
patients O 0
. O 0

The O 0
plasticity O 0
of O 0
primary O 0
motor O 0
cortex O 0
( O 0
M1 O 0
) O 0
in O 0
patients O 0
with O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
( O 0
PD B-Disease 0
) O 0
and O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
( O 0
LIDs B-Disease 0
) O 0
is O 0
severely O 0
impaired O 0
. O 0

We O 0
recently O 0
reported O 0
in O 0
young O 0
healthy O 0
subjects O 0
that O 0
inhibitory O 0
cerebellar O 0
stimulation O 0
enhanced O 0
the O 0
sensorimotor O 0
plasticity O 0
of O 0
M1 O 0
that O 0
was O 0
induced O 0
by O 0
paired O 0
associative O 0
stimulation O 0
( O 0
PAS O 0
) O 0
. O 0

This O 0
study O 0
demonstrates O 0
that O 0
the O 0
deficient O 0
sensorimotor O 0
M1 O 0
plasticity O 0
in O 0
16 O 0
patients O 0
with O 0
LIDs B-Disease 0
could O 0
be O 0
reinstated O 0
by O 0
a O 0
single O 0
session O 0
of O 0
real O 0
inhibitory O 0
cerebellar O 0
stimulation O 0
but O 0
not O 0
sham O 0
stimulation O 0
. O 0

This O 0
was O 0
evident O 0
only O 0
when O 0
a O 0
sensory O 0
component O 0
was O 0
involved O 0
in O 0
the O 0
induction O 0
of O 0
plasticity O 0
, O 0
indicating O 0
that O 0
cerebellar O 0
sensory O 0
processing O 0
function O 0
is O 0
involved O 0
in O 0
the O 0
resurgence O 0
of O 0
M1 O 0
plasticity O 0
. O 0

The O 0
benefit O 0
of O 0
inhibitory O 0
cerebellar O 0
stimulation O 0
on O 0
LIDs B-Disease 0
is O 0
known O 0
. O 0

To O 0
explore O 0
whether O 0
this O 0
benefit O 0
is O 0
linked O 0
to O 0
the O 0
restoration O 0
of O 0
sensorimotor O 0
plasticity O 0
of O 0
M1 O 0
, O 0
we O 0
conducted O 0
an O 0
additional O 0
study O 0
looking O 0
at O 0
changes O 0
in O 0
LIDs B-Disease 0
and O 0
PAS O 0
- O 0
induced O 0
plasticity O 0
after O 0
10 O 0
sessions O 0
of O 0
either O 0
bilateral O 0
, O 0
real O 0
inhibitory O 0
cerebellar O 0
stimulation O 0
or O 0
sham O 0
stimulation O 0
. O 0

Only O 0
real O 0
and O 0
not O 0
sham O 0
stimulation O 0
had O 0
an O 0
antidyskinetic O 0
effect O 0
and O 0
it O 0
was O 0
paralleled O 0
by O 0
a O 0
resurgence O 0
in O 0
the O 0
sensorimotor O 0
plasticity O 0
of O 0
M1 O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
alterations O 0
in O 0
cerebellar O 0
sensory O 0
processing O 0
function O 0
, O 0
occurring O 0
secondary O 0
to O 0
abnormal O 0
basal O 0
ganglia O 0
signals O 0
reaching O 0
it O 0
, O 0
may O 0
be O 0
an O 0
important O 0
element O 0
contributing O 0
to O 0
the O 0
maladaptive O 0
sensorimotor O 0
plasticity O 0
of O 0
M1 O 0
and O 0
the O 0
emergence O 0
of O 0
abnormal B-Disease 0
involuntary I-Disease 0
movements I-Disease 0
. O 0

The O 0
long O 0
- O 0
term O 0
safety O 0
of O 0
danazol B-Chemical 0
in O 0
women O 0
with O 0
hereditary B-Disease 0
angioedema I-Disease 0
. O 0

Although O 0
the O 0
short O 0
- O 0
term O 0
safety O 0
( O 0
less O 0
than O 0
or O 0
equal O 0
to O 0
6 O 0
months O 0
) O 0
of O 0
danazol B-Chemical 0
has O 0
been O 0
established O 0
in O 0
a O 0
variety O 0
of O 0
settings O 0
, O 0
no O 0
information O 0
exists O 0
as O 0
to O 0
its O 0
long O 0
- O 0
term O 0
safety O 0
. O 0

We O 0
therefore O 0
investigated O 0
the O 0
long O 0
- O 0
term O 0
safety O 0
of O 0
danazol B-Chemical 0
by O 0
performing O 0
a O 0
retrospective O 0
chart O 0
review O 0
of O 0
60 O 0
female O 0
patients O 0
with O 0
hereditary B-Disease 0
angioedema I-Disease 0
treated O 0
with O 0
danazol B-Chemical 0
for O 0
a O 0
continuous O 0
period O 0
of O 0
6 O 0
months O 0
or O 0
longer O 0
. O 0

The O 0
mean O 0
age O 0
of O 0
the O 0
patients O 0
was O 0
35 O 0
. O 0
2 O 0
years O 0
and O 0
the O 0
mean O 0
duration O 0
of O 0
therapy O 0
was O 0
59 O 0
. O 0
7 O 0
months O 0
. O 0

Virtually O 0
all O 0
patients O 0
experienced O 0
one O 0
or O 0
more O 0
adverse O 0
reactions O 0
. O 0

Menstrual B-Disease 0
abnormalities I-Disease 0
( O 0
79 O 0
% O 0
) O 0
, O 0
weight B-Disease 0
gain I-Disease 0
( O 0
60 O 0
% O 0
) O 0
, O 0
muscle B-Disease 0
cramps I-Disease 0
/ O 0
myalgias B-Disease 0
( O 0
40 O 0
% O 0
) O 0
, O 0
and O 0
transaminase O 0
elevations O 0
( O 0
40 O 0
% O 0
) O 0
were O 0
the O 0
most O 0
common O 0
adverse O 0
reactions O 0
. O 0

The O 0
drug O 0
was O 0
discontinued O 0
due O 0
to O 0
adverse O 0
reactions O 0
in O 0
8 O 0
patients O 0
. O 0

No O 0
patient O 0
has O 0
died O 0
or O 0
suffered O 0
any O 0
apparent O 0
long O 0
- O 0
term O 0
sequelae O 0
that O 0
were O 0
directly O 0
attributable O 0
to O 0
the O 0
drug O 0
. O 0

We O 0
conclude O 0
that O 0
, O 0
despite O 0
a O 0
relatively O 0
high O 0
incidence O 0
of O 0
adverse O 0
reactions O 0
, O 0
danazol B-Chemical 0
has O 0
proven O 0
to O 0
be O 0
remarkably O 0
safe O 0
over O 0
the O 0
long O 0
- O 0
term O 0
in O 0
this O 0
group O 0
of O 0
patients O 0
. O 0

The O 0
function O 0
of O 0
P2X3 O 0
receptor O 0
and O 0
NK1 O 0
receptor O 0
antagonists O 0
on O 0
cyclophosphamide B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
in O 0
rats O 0
. O 0

PURPOSE O 0
: O 0
The O 0
purpose O 0
of O 0
the O 0
study O 0
is O 0
to O 0
explore O 0
the O 0
function O 0
of O 0
P2X3 O 0
and O 0
NK1 O 0
receptors O 0
antagonists O 0
on O 0
cyclophosphamide B-Chemical 0
( O 0
CYP B-Chemical 0
) O 0
- O 0
induced O 0
cystitis B-Disease 0
in O 0
rats O 0
. O 0

METHODS O 0
: O 0
Sixty O 0
female O 0
Sprague O 0
- O 0
Dawley O 0
( O 0
SD O 0
) O 0
rats O 0
were O 0
randomly O 0
divided O 0
into O 0
three O 0
groups O 0
. O 0

The O 0
rats O 0
in O 0
the O 0
control O 0
group O 0
were O 0
intraperitoneally O 0
( O 0
i O 0
. O 0
p O 0
. O 0
) O 0
injected O 0
with O 0
0 O 0
. O 0
9 O 0
% O 0
saline O 0
( O 0
4 O 0
ml O 0
/ O 0
kg O 0
) O 0
; O 0
the O 0
rats O 0
in O 0
the O 0
model O 0
group O 0
were O 0
i O 0
. O 0
p O 0
. O 0
injected O 0
with O 0
CYP B-Chemical 0
( O 0
150 O 0
mg O 0
/ O 0
kg O 0
) O 0
; O 0
and O 0
the O 0
rats O 0
in O 0
the O 0
intervention O 0
group O 0
were O 0
i O 0
. O 0
p O 0
. O 0
injected O 0
with O 0
CYP B-Chemical 0
with O 0
subsequently O 0
perfusion O 0
of O 0
bladder O 0
with O 0
P2X3 O 0
and O 0
NK1 O 0
receptors O 0
' O 0
antagonists O 0
, O 0
Suramin B-Chemical 0
and O 0
GR B-Chemical 0
82334 I-Chemical 0
. O 0

Spontaneous O 0
pain B-Disease 0
behaviors O 0
following O 0
the O 0
administration O 0
of O 0
CYP B-Chemical 0
were O 0
observed O 0
. O 0

Urodynamic O 0
parameters O 0
, O 0
bladder O 0
pressure O 0
- O 0
volume O 0
curve O 0
, O 0
maximum O 0
voiding O 0
pressure O 0
( O 0
MVP O 0
) O 0
, O 0
and O 0
maximum O 0
cystometric O 0
capacity O 0
( O 0
MCC O 0
) O 0
, O 0
were O 0
recorded O 0
. O 0

Pathological O 0
changes O 0
in O 0
bladder O 0
tissue O 0
were O 0
observed O 0
. O 0

Immunofluorescence O 0
was O 0
used O 0
to O 0
detect O 0
the O 0
expression O 0
of O 0
P2X3 O 0
and O 0
NK1 O 0
receptors O 0
in O 0
bladder O 0
. O 0

RESULTS O 0
: O 0
Cyclophosphamide B-Chemical 0
treatment O 0
increased O 0
the O 0
spontaneous O 0
pain B-Disease 0
behaviors O 0
scores O 0
. O 0

The O 0
incidence O 0
of O 0
bladder O 0
instability O 0
during O 0
urine O 0
storage O 0
period O 0
of O 0
model O 0
group O 0
was O 0
significantly O 0
higher O 0
than O 0
intervention O 0
group O 0
( O 0
X O 0
( O 0
2 O 0
) O 0
= O 0
7 O 0
. O 0
619 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
007 O 0
) O 0
and O 0
control O 0
group O 0
( O 0
X O 0
( O 0
2 O 0
) O 0
= O 0
13 O 0
. O 0
755 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
000 O 0
) O 0
. O 0

MCC O 0
in O 0
the O 0
model O 0
group O 0
was O 0
lower O 0
than O 0
the O 0
control O 0
and O 0
intervention O 0
groups O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Histological O 0
changes O 0
evident O 0
in O 0
model O 0
and O 0
intervention O 0
groups O 0
rats O 0
' O 0
bladder O 0
included O 0
edema B-Disease 0
, O 0
vasodilation O 0
, O 0
and O 0
infiltration O 0
of O 0
inflammatory O 0
cells O 0
. O 0

In O 0
model O 0
group O 0
, O 0
the O 0
expression O 0
of O 0
P2X3 O 0
receptor O 0
increased O 0
in O 0
urothelium O 0
and O 0
suburothelium O 0
, O 0
and O 0
NK1 O 0
receptor O 0
increased O 0
in O 0
suburothelium O 0
, O 0
while O 0
the O 0
expression O 0
of O 0
them O 0
in O 0
intervention O 0
group O 0
was O 0
lower O 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
CYP B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
, O 0
the O 0
expression O 0
of O 0
P2X3 O 0
and O 0
NK1 O 0
receptors O 0
increased O 0
in O 0
urothelium O 0
and O 0
/ O 0
or O 0
suburothelium O 0
. O 0

Perfusion O 0
of O 0
bladder O 0
with O 0
P2X3 O 0
and O 0
NK1 O 0
receptors O 0
antagonists O 0
ameliorated O 0
the O 0
bladder O 0
function O 0
. O 0

Patient O 0
tolerance O 0
study O 0
of O 0
topical O 0
chlorhexidine B-Chemical 0
diphosphanilate I-Chemical 0
: O 0
a O 0
new O 0
topical O 0
agent O 0
for O 0
burns B-Disease 0
. O 0

Effective O 0
topical O 0
antimicrobial O 0
agents O 0
decrease O 0
infection B-Disease 0
and O 0
mortality O 0
in O 0
burn B-Disease 0
patients O 0
. O 0

Chlorhexidine B-Chemical 0
phosphanilate I-Chemical 0
( O 0
CHP B-Chemical 0
) O 0
, O 0
a O 0
new O 0
broad O 0
- O 0
spectrum O 0
antimicrobial O 0
agent O 0
, O 0
has O 0
been O 0
evaluated O 0
as O 0
a O 0
topical O 0
burn B-Disease 0
wound O 0
dressing O 0
in O 0
cream O 0
form O 0
, O 0
but O 0
preliminary O 0
clinical O 0
trials O 0
reported O 0
that O 0
it O 0
was O 0
painful O 0
upon O 0
application O 0
. O 0

This O 0
study O 0
compared O 0
various O 0
concentrations O 0
of O 0
CHP B-Chemical 0
to O 0
determine O 0
if O 0
a O 0
tolerable O 0
concentration O 0
could O 0
be O 0
identified O 0
with O 0
retention O 0
of O 0
antimicrobial O 0
efficacy O 0
. O 0

Twenty O 0
- O 0
nine O 0
burn B-Disease 0
patients O 0
, O 0
each O 0
with O 0
two O 0
similar O 0
burns B-Disease 0
which O 0
could O 0
be O 0
separately O 0
treated O 0
, O 0
were O 0
given O 0
pairs O 0
of O 0
treatments O 0
at O 0
successive O 0
12 O 0
- O 0
h O 0
intervals O 0
over O 0
a O 0
3 O 0
- O 0
day O 0
period O 0
. O 0

One O 0
burn B-Disease 0
site O 0
was O 0
treated O 0
with O 0
each O 0
of O 0
four O 0
different O 0
CHP B-Chemical 0
concentrations O 0
, O 0
from O 0
0 O 0
. O 0
25 O 0
per O 0
cent O 0
to O 0
2 O 0
per O 0
cent O 0
, O 0
their O 0
vehicle O 0
, O 0
and O 0
1 O 0
per O 0
cent O 0
silver B-Chemical 0
sulphadiazine I-Chemical 0
( O 0
AgSD B-Chemical 0
) O 0
cream O 0
, O 0
an O 0
antimicrobial O 0
agent O 0
frequently O 0
used O 0
for O 0
topical O 0
treatment O 0
of O 0
burn B-Disease 0
wounds O 0
. O 0

The O 0
other O 0
site O 0
was O 0
always O 0
treated O 0
with O 0
AgSD B-Chemical 0
cream O 0
. O 0

There O 0
was O 0
a O 0
direct O 0
relationship O 0
between O 0
CHP B-Chemical 0
concentration O 0
and O 0
patients O 0
' O 0
ratings O 0
of O 0
pain B-Disease 0
on O 0
an O 0
analogue O 0
scale O 0
. O 0

The O 0
0 O 0
. O 0
25 O 0
per O 0
cent O 0
CHP B-Chemical 0
cream O 0
was O 0
closest O 0
to O 0
AgSD B-Chemical 0
in O 0
pain B-Disease 0
tolerance O 0
; O 0
however O 0
, O 0
none O 0
of O 0
the O 0
treatments O 0
differed O 0
statistically O 0
from O 0
AgSD B-Chemical 0
or O 0
from O 0
each O 0
other O 0
. O 0

In O 0
addition O 0
, O 0
ease O 0
of O 0
application O 0
of O 0
CHP B-Chemical 0
creams O 0
was O 0
less O 0
satisfactory O 0
than O 0
that O 0
of O 0
AgSD B-Chemical 0
. O 0

It O 0
was O 0
concluded O 0
that O 0
formulations O 0
at O 0
or O 0
below O 0
0 O 0
. O 0
5 O 0
per O 0
cent O 0
CHP B-Chemical 0
may O 0
prove O 0
acceptable O 0
for O 0
wound O 0
care O 0
, O 0
but O 0
the O 0
vehicle O 0
system O 0
needs O 0
pharmaceutical O 0
improvement O 0
to O 0
render O 0
it O 0
more O 0
tolerable O 0
and O 0
easier O 0
to O 0
use O 0
. O 0

Acute O 0
hepatitis B-Disease 0
associated O 0
with O 0
clopidogrel B-Chemical 0
: O 0
a O 0
case O 0
report O 0
and O 0
review O 0
of O 0
the O 0
literature O 0
. O 0

Drug O 0
- O 0
induced O 0
hepatotoxicity B-Disease 0
is O 0
a O 0
common O 0
cause O 0
of O 0
acute O 0
hepatitis B-Disease 0
, O 0
and O 0
the O 0
recognition O 0
of O 0
the O 0
responsible O 0
drug O 0
may O 0
be O 0
difficult O 0
. O 0

We O 0
describe O 0
a O 0
case O 0
of O 0
clopidogrel B-Chemical 0
- O 0
related O 0
acute O 0
hepatitis B-Disease 0
. O 0

The O 0
diagnosis O 0
is O 0
strongly O 0
suggested O 0
by O 0
an O 0
accurate O 0
medical O 0
history O 0
and O 0
liver O 0
biopsy O 0
. O 0

Reports O 0
about O 0
cases O 0
of O 0
hepatotoxicity B-Disease 0
due O 0
to O 0
clopidogrel B-Chemical 0
are O 0
increasing O 0
in O 0
the O 0
last O 0
few O 0
years O 0
, O 0
after O 0
the O 0
increased O 0
use O 0
of O 0
this O 0
drug O 0
. O 0

In O 0
conclusion O 0
, O 0
we O 0
believe O 0
that O 0
physicians O 0
should O 0
carefully O 0
consider O 0
the O 0
risk O 0
of O 0
drug O 0
- O 0
induced O 0
hepatic B-Disease 0
injury I-Disease 0
when O 0
clopidogrel B-Chemical 0
is O 0
prescribed O 0
. O 0

Bortezomib B-Chemical 0
and O 0
dexamethasone B-Chemical 0
as O 0
salvage O 0
therapy O 0
in O 0
patients O 0
with O 0
relapsed O 0
/ O 0
refractory O 0
multiple B-Disease 0
myeloma I-Disease 0
: O 0
analysis O 0
of O 0
long O 0
- O 0
term O 0
clinical O 0
outcomes O 0
. O 0

Bortezomib B-Chemical 0
( O 0
bort B-Chemical 0
) O 0
- O 0
dexamethasone B-Chemical 0
( O 0
dex B-Chemical 0
) O 0
is O 0
an O 0
effective O 0
therapy O 0
for O 0
relapsed O 0
/ O 0
refractory O 0
( O 0
R O 0
/ O 0
R O 0
) O 0
multiple B-Disease 0
myeloma I-Disease 0
( O 0
MM B-Disease 0
) O 0
. O 0

This O 0
retrospective O 0
study O 0
investigated O 0
the O 0
combination O 0
of O 0
bort B-Chemical 0
( O 0
1 O 0
. O 0
3 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
on O 0
days O 0
1 O 0
, O 0
4 O 0
, O 0
8 O 0
, O 0
and O 0
11 O 0
every O 0
3 O 0
weeks O 0
) O 0
and O 0
dex B-Chemical 0
( O 0
20 O 0
mg O 0
on O 0
the O 0
day O 0
of O 0
and O 0
the O 0
day O 0
after O 0
bort B-Chemical 0
) O 0
as O 0
salvage O 0
treatment O 0
in O 0
85 O 0
patients O 0
with O 0
R O 0
/ O 0
R O 0
MM B-Disease 0
after O 0
prior O 0
autologous O 0
stem O 0
cell O 0
transplantation O 0
or O 0
conventional O 0
chemotherapy O 0
. O 0

The O 0
median O 0
number O 0
of O 0
prior O 0
lines O 0
of O 0
therapy O 0
was O 0
2 O 0
. O 0

Eighty O 0
- O 0
seven O 0
percent O 0
of O 0
the O 0
patients O 0
had O 0
received O 0
immunomodulatory O 0
drugs O 0
included O 0
in O 0
some O 0
line O 0
of O 0
therapy O 0
before O 0
bort B-Chemical 0
- O 0
dex B-Chemical 0
. O 0

The O 0
median O 0
number O 0
of O 0
bort B-Chemical 0
- O 0
dex B-Chemical 0
cycles O 0
was O 0
6 O 0
, O 0
up O 0
to O 0
a O 0
maximum O 0
of O 0
12 O 0
cycles O 0
. O 0

On O 0
an O 0
intention O 0
- O 0
to O 0
- O 0
treat O 0
basis O 0
, O 0
55 O 0
% O 0
of O 0
the O 0
patients O 0
achieved O 0
at O 0
least O 0
partial O 0
response O 0
, O 0
including O 0
19 O 0
% O 0
CR O 0
and O 0
35 O 0
% O 0
achieved O 0
at O 0
least O 0
very O 0
good O 0
partial O 0
response O 0
. O 0

Median O 0
durations O 0
of O 0
response O 0
, O 0
time O 0
to O 0
next O 0
therapy O 0
and O 0
treatment O 0
- O 0
free O 0
interval O 0
were O 0
8 O 0
, O 0
11 O 0
. O 0
2 O 0
, O 0
and O 0
5 O 0
. O 0
1 O 0
months O 0
, O 0
respectively O 0
. O 0

The O 0
most O 0
relevant O 0
adverse O 0
event O 0
was O 0
peripheral B-Disease 0
neuropathy I-Disease 0
, O 0
which O 0
occurred O 0
in O 0
78 O 0
% O 0
of O 0
the O 0
patients O 0
( O 0
grade O 0
II O 0
, O 0
38 O 0
% O 0
; O 0
grade O 0
III O 0
, O 0
21 O 0
% O 0
) O 0
and O 0
led O 0
to O 0
treatment O 0
discontinuation O 0
in O 0
6 O 0
% O 0
. O 0

With O 0
a O 0
median O 0
follow O 0
up O 0
of O 0
22 O 0
months O 0
, O 0
median O 0
time O 0
to O 0
progression O 0
, O 0
progression O 0
- O 0
free O 0
survival O 0
( O 0
PFS O 0
) O 0
and O 0
overall O 0
survival O 0
( O 0
OS O 0
) O 0
were O 0
8 O 0
. O 0
9 O 0
, O 0
8 O 0
. O 0
7 O 0
, O 0
and O 0
22 O 0
months O 0
, O 0
respectively O 0
. O 0

Prolonged O 0
PFS O 0
and O 0
OS O 0
were O 0
observed O 0
in O 0
patients O 0
achieving O 0
CR O 0
and O 0
receiving O 0
bort B-Chemical 0
- O 0
dex B-Chemical 0
a O 0
single O 0
line O 0
of O 0
prior O 0
therapy O 0
. O 0

Bort B-Chemical 0
- O 0
dex B-Chemical 0
was O 0
an O 0
effective O 0
salvage O 0
treatment O 0
for O 0
MM B-Disease 0
patients O 0
, O 0
particularly O 0
for O 0
those O 0
in O 0
first O 0
relapse O 0
. O 0

Pubertal O 0
exposure O 0
to O 0
Bisphenol B-Chemical 0
A I-Chemical 0
increases O 0
anxiety B-Disease 0
- O 0
like O 0
behavior O 0
and O 0
decreases O 0
acetylcholinesterase O 0
activity O 0
of O 0
hippocampus O 0
in O 0
adult O 0
male O 0
mice O 0
. O 0

The O 0
negative O 0
effects O 0
of O 0
Bisphenol B-Chemical 0
A I-Chemical 0
( O 0
BPA B-Chemical 0
) O 0
on O 0
neurodevelopment O 0
and O 0
behaviors O 0
have O 0
been O 0
well O 0
established O 0
. O 0

Acetylcholinesterase O 0
( O 0
AChE O 0
) O 0
is O 0
a O 0
regulatory O 0
enzyme O 0
which O 0
is O 0
involved O 0
in O 0
anxiety B-Disease 0
- O 0
like O 0
behavior O 0
. O 0

This O 0
study O 0
investigated O 0
behavioral O 0
phenotypes O 0
and O 0
AChE O 0
activity O 0
in O 0
male O 0
mice O 0
following O 0
BPA B-Chemical 0
exposure O 0
during O 0
puberty O 0
. O 0

On O 0
postnatal O 0
day O 0
( O 0
PND O 0
) O 0
35 O 0
, O 0
male O 0
mice O 0
were O 0
exposed O 0
to O 0
50mg O 0
BPA B-Chemical 0
/ O 0
kg O 0
diet O 0
per O 0
day O 0
for O 0
a O 0
period O 0
of O 0
35 O 0
days O 0
. O 0

On O 0
PND71 O 0
, O 0
a O 0
behavioral O 0
assay O 0
was O 0
performed O 0
using O 0
the O 0
elevated O 0
plus O 0
maze O 0
( O 0
EPM O 0
) O 0
and O 0
the O 0
light O 0
/ O 0
dark O 0
test O 0
. O 0

In O 0
addition O 0
, O 0
AChE O 0
activity O 0
was O 0
measured O 0
in O 0
the O 0
prefrontal O 0
cortex O 0
, O 0
hypothalamus O 0
, O 0
cerebellum O 0
and O 0
hippocampus O 0
. O 0

Results O 0
from O 0
our O 0
behavioral O 0
phenotyping O 0
indicated O 0
that O 0
anxiety B-Disease 0
- O 0
like O 0
behavior O 0
was O 0
increased O 0
in O 0
mice O 0
exposed O 0
to O 0
BPA B-Chemical 0
. O 0

AChE O 0
activity O 0
was O 0
significantly O 0
decreased O 0
in O 0
the O 0
hippocampus O 0
of O 0
mice O 0
with O 0
BPA B-Chemical 0
compared O 0
to O 0
control O 0
mice O 0
, O 0
whereas O 0
no O 0
difference O 0
was O 0
found O 0
in O 0
the O 0
prefrontal O 0
cortex O 0
, O 0
hypothalamus O 0
and O 0
cerebellum O 0
. O 0

Our O 0
findings O 0
showed O 0
that O 0
pubertal O 0
BPA B-Chemical 0
exposure O 0
increased O 0
anxiety B-Disease 0
- O 0
like O 0
behavior O 0
, O 0
which O 0
may O 0
be O 0
associated O 0
with O 0
decreased O 0
AChE O 0
activity O 0
of O 0
the O 0
hippocampus O 0
in O 0
adult O 0
male O 0
mice O 0
. O 0

Further O 0
studies O 0
are O 0
necessary O 0
to O 0
investigate O 0
the O 0
cholinergic O 0
signaling O 0
of O 0
the O 0
hippocampus O 0
in O 0
PBE O 0
induced O 0
anxiety B-Disease 0
- O 0
like O 0
behaviors O 0
. O 0

Biochemical O 0
effects O 0
of O 0
Solidago O 0
virgaurea O 0
extract O 0
on O 0
experimental O 0
cardiotoxicity B-Disease 0
. O 0

Cardiovascular B-Disease 0
diseases I-Disease 0
( O 0
CVDs B-Disease 0
) O 0
are O 0
the O 0
major O 0
health O 0
problem O 0
of O 0
advanced O 0
as O 0
well O 0
as O 0
developing O 0
countries O 0
of O 0
the O 0
world O 0
. O 0

The O 0
aim O 0
of O 0
the O 0
present O 0
study O 0
was O 0
to O 0
investigate O 0
the O 0
protective O 0
effect O 0
of O 0
the O 0
Solidago O 0
virgaurea O 0
extract O 0
on O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
in O 0
rats O 0
. O 0

The O 0
subcutaneous O 0
injection O 0
of O 0
isoproterenol B-Chemical 0
( O 0
30 O 0
mg O 0
/ O 0
kg O 0
) O 0
into O 0
rats O 0
twice O 0
at O 0
an O 0
interval O 0
of O 0
24 O 0
h O 0
, O 0
for O 0
two O 0
consecutive O 0
days O 0
, O 0
led O 0
to O 0
a O 0
significant O 0
increase O 0
in O 0
serum O 0
lactate B-Chemical 0
dehydrogenase O 0
, O 0
creatine B-Chemical 0
phosphokinase O 0
, O 0
alanine B-Chemical 0
transaminase O 0
, O 0
aspartate B-Chemical 0
transaminase O 0
, O 0
and O 0
angiotensin B-Chemical 0
- O 0
converting O 0
enzyme O 0
activities O 0
, O 0
total O 0
cholesterol B-Chemical 0
, O 0
triglycerides B-Chemical 0
, O 0
free O 0
serum O 0
fatty B-Chemical 0
acid I-Chemical 0
, O 0
cardiac O 0
tissue O 0
malondialdehyde B-Chemical 0
( O 0
MDA B-Chemical 0
) O 0
, O 0
and O 0
nitric B-Chemical 0
oxide I-Chemical 0
levels O 0
and O 0
a O 0
significant O 0
decrease O 0
in O 0
levels O 0
of O 0
glutathione B-Chemical 0
and O 0
superoxide B-Chemical 0
dismutase O 0
in O 0
cardiac O 0
tissue O 0
as O 0
compared O 0
to O 0
the O 0
normal O 0
control O 0
group O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Pretreatment O 0
with O 0
S O 0
. O 0
virgaurea O 0
extract O 0
for O 0
5 O 0
weeks O 0
at O 0
a O 0
dose O 0
of O 0
250 O 0
mg O 0
/ O 0
kg O 0
followed O 0
by O 0
isoproterenol B-Chemical 0
injection O 0
significantly O 0
prevented O 0
the O 0
observed O 0
alterations O 0
. O 0

Captopril B-Chemical 0
( O 0
50 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
, O 0
given O 0
orally O 0
) O 0
, O 0
an O 0
inhibitor O 0
of O 0
angiotensin B-Chemical 0
- O 0
converting O 0
enzyme O 0
used O 0
as O 0
a O 0
standard O 0
cardioprotective O 0
drug O 0
, O 0
was O 0
used O 0
as O 0
a O 0
positive O 0
control O 0
in O 0
this O 0
study O 0
. O 0

The O 0
data O 0
of O 0
the O 0
present O 0
study O 0
suggest O 0
that O 0
S O 0
. O 0
virgaurea O 0
extract O 0
exerts O 0
its O 0
protective O 0
effect O 0
by O 0
decreasing O 0
MDA B-Chemical 0
level O 0
and O 0
increasing O 0
the O 0
antioxidant O 0
status O 0
in O 0
isoproterenol B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

The O 0
study O 0
emphasizes O 0
the O 0
beneficial O 0
action O 0
of O 0
S O 0
. O 0
virgaurea O 0
extract O 0
as O 0
a O 0
cardioprotective O 0
agent O 0
. O 0

" O 0
Real O 0
- O 0
world O 0
" O 0
data O 0
on O 0
the O 0
efficacy O 0
and O 0
safety O 0
of O 0
lenalidomide B-Chemical 0
and O 0
dexamethasone B-Chemical 0
in O 0
patients O 0
with O 0
relapsed O 0
/ O 0
refractory O 0
multiple B-Disease 0
myeloma I-Disease 0
who O 0
were O 0
treated O 0
according O 0
to O 0
the O 0
standard O 0
clinical O 0
practice O 0
: O 0
a O 0
study O 0
of O 0
the O 0
Greek O 0
Myeloma B-Disease 0
Study O 0
Group O 0
. O 0

Lenalidomide B-Chemical 0
and O 0
dexamethasone B-Chemical 0
( O 0
RD B-Chemical 0
) O 0
is O 0
a O 0
standard O 0
of O 0
care O 0
for O 0
relapsed O 0
/ O 0
refractory O 0
multiple B-Disease 0
myeloma I-Disease 0
( O 0
RRMM B-Disease 0
) O 0
, O 0
but O 0
there O 0
is O 0
limited O 0
published O 0
data O 0
on O 0
its O 0
efficacy O 0
and O 0
safety O 0
in O 0
the O 0
" O 0
real O 0
world O 0
" O 0
( O 0
RW O 0
) O 0
, O 0
according O 0
to O 0
the O 0
International O 0
Society O 0
of O 0
Pharmacoeconomics O 0
and O 0
Outcomes O 0
Research O 0
definition O 0
. O 0

We O 0
studied O 0
212 O 0
RRMM B-Disease 0
patients O 0
who O 0
received O 0
RD B-Chemical 0
in O 0
RW O 0
. O 0

Objective O 0
response O 0
( O 0
> O 0
PR O 0
( O 0
partial O 0
response O 0
) O 0
) O 0
rate O 0
was O 0
77 O 0
. O 0
4 O 0
% O 0
( O 0
complete O 0
response O 0
( O 0
CR O 0
) O 0
, O 0
20 O 0
. O 0
2 O 0
% O 0
) O 0
. O 0

Median O 0
time O 0
to O 0
first O 0
and O 0
best O 0
response O 0
was O 0
2 O 0
and O 0
5 O 0
months O 0
, O 0
respectively O 0
. O 0

Median O 0
time O 0
to O 0
CR O 0
when O 0
RD B-Chemical 0
was O 0
given O 0
as O 0
2nd O 0
or O 0
> O 0
2 O 0
( O 0
nd O 0
) O 0
- O 0
line O 0
treatment O 0
at O 0
4 O 0
and O 0
11 O 0
months O 0
, O 0
respectively O 0
. O 0

Quality O 0
of O 0
response O 0
was O 0
independent O 0
of O 0
previous O 0
lines O 0
of O 0
therapies O 0
or O 0
previous O 0
exposure O 0
to O 0
thalidomide B-Chemical 0
or O 0
bortezomib B-Chemical 0
. O 0

Median O 0
duration O 0
of O 0
response O 0
was O 0
34 O 0
. O 0
4 O 0
months O 0
, O 0
and O 0
it O 0
was O 0
higher O 0
in O 0
patients O 0
who O 0
received O 0
RD B-Chemical 0
until O 0
progression O 0
( O 0
not O 0
reached O 0
versus O 0
19 O 0
months O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Improvement O 0
of O 0
humoral O 0
immunity O 0
occurred O 0
in O 0
60 O 0
% O 0
of O 0
responders O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
and O 0
in O 0
the O 0
majority O 0
of O 0
patients O 0
who O 0
achieved O 0
stable O 0
disease O 0
. O 0

Adverse O 0
events O 0
were O 0
reported O 0
in O 0
68 O 0
. O 0
9 O 0
% O 0
of O 0
patients O 0
( O 0
myelosuppression B-Disease 0
in O 0
49 O 0
. O 0
4 O 0
% O 0
) O 0
and O 0
12 O 0
. O 0
7 O 0
% O 0
of O 0
patients O 0
needed O 0
hospitalization O 0
. O 0

Peripheral B-Disease 0
neuropathy I-Disease 0
was O 0
observed O 0
only O 0
in O 0
2 O 0
. O 0
5 O 0
% O 0
of O 0
patients O 0
and O 0
deep B-Disease 0
vein I-Disease 0
thrombosis I-Disease 0
in O 0
5 O 0
. O 0
7 O 0
% O 0
. O 0

Dose O 0
reductions O 0
were O 0
needed O 0
in O 0
31 O 0
% O 0
of O 0
patients O 0
and O 0
permanent O 0
discontinuation O 0
in O 0
38 O 0
. O 0
9 O 0
% O 0
. O 0

Median O 0
time O 0
to O 0
treatment O 0
discontinuation O 0
was O 0
16 O 0
. O 0
8 O 0
months O 0
. O 0

Performance O 0
status O 0
( O 0
PS O 0
) O 0
and O 0
initial O 0
lenalidomide B-Chemical 0
dose O 0
predicted O 0
for O 0
treatment O 0
discontinuation O 0
. O 0

Extra O 0
- O 0
medullary O 0
relapses O 0
occurred O 0
in O 0
3 O 0
. O 0
8 O 0
% O 0
of O 0
patients O 0
. O 0

Our O 0
study O 0
confirms O 0
that O 0
RD B-Chemical 0
is O 0
effective O 0
and O 0
safe O 0
in O 0
RRMM B-Disease 0
in O 0
the O 0
RW O 0
; O 0
it O 0
produces O 0
durable O 0
responses O 0
especially O 0
in O 0
patients O 0
who O 0
continue O 0
on O 0
treatment O 0
till O 0
progression O 0
and O 0
improves O 0
humoral O 0
immunity O 0
even O 0
in O 0
patients O 0
with O 0
stable O 0
disease O 0
. O 0

The O 0
cytogenetic O 0
action O 0
of O 0
ifosfamide B-Chemical 0
, O 0
mesna B-Chemical 0
, O 0
and O 0
their O 0
combination O 0
on O 0
peripheral O 0
rabbit O 0
lymphocytes O 0
: O 0
an O 0
in O 0
vivo O 0
/ O 0
in O 0
vitro O 0
cytogenetic O 0
study O 0
. O 0

Ifosfamide B-Chemical 0
( O 0
IFO B-Chemical 0
) O 0
is O 0
an O 0
alkylating O 0
nitrogen B-Chemical 0
mustard O 0
, O 0
administrated O 0
as O 0
an O 0
antineoplasmic O 0
agent O 0
. O 0

It O 0
is O 0
characterized O 0
by O 0
its O 0
intense O 0
urotoxic O 0
action O 0
, O 0
leading O 0
to O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
. O 0

This O 0
side O 0
effect O 0
of O 0
IFO B-Chemical 0
raises O 0
the O 0
requirement O 0
for O 0
the O 0
co O 0
- O 0
administration O 0
with O 0
sodium B-Chemical 0
2 I-Chemical 0
- I-Chemical 0
sulfanylethanesulfonate I-Chemical 0
( O 0
Mesna B-Chemical 0
) O 0
aiming O 0
to O 0
avoid O 0
or O 0
minimize O 0
this O 0
effect O 0
. O 0

IFO B-Chemical 0
and O 0
Mesna B-Chemical 0
were O 0
administrated O 0
separately O 0
on O 0
rabbit O 0
' O 0
s O 0
lymphocytes O 0
in O 0
vivo O 0
, O 0
which O 0
were O 0
later O 0
developed O 0
in O 0
vitro O 0
. O 0

Cytogenetic O 0
markers O 0
for O 0
sister O 0
chromatid O 0
exchanges O 0
( O 0
SCEs O 0
) O 0
, O 0
proliferation O 0
rate O 0
index O 0
( O 0
PRI O 0
) O 0
and O 0
Mitotic O 0
Index O 0
were O 0
recorded O 0
. O 0

Mesna B-Chemical 0
' O 0
s O 0
action O 0
, O 0
in O 0
conjunction O 0
with O 0
IFO B-Chemical 0
reduces O 0
the O 0
frequency O 0
of O 0
SCEs O 0
, O 0
in O 0
comparison O 0
with O 0
the O 0
SCEs O 0
recordings O 0
obtained O 0
when O 0
IFO B-Chemical 0
is O 0
administered O 0
alone O 0
. O 0

In O 0
addition O 0
to O 0
this O 0
, O 0
when O 0
high O 0
concentrations O 0
of O 0
Mesna B-Chemical 0
were O 0
administered O 0
alone O 0
significant O 0
reductions O 0
of O 0
the O 0
PRI O 0
were O 0
noted O 0
, O 0
than O 0
with O 0
IFO B-Chemical 0
acting O 0
at O 0
the O 0
same O 0
concentration O 0
on O 0
the O 0
lymphocytes O 0
. O 0

Mesna B-Chemical 0
significantly O 0
reduces O 0
IFO B-Chemical 0
' O 0
s O 0
genotoxicity B-Disease 0
, O 0
while O 0
when O 0
administered O 0
in O 0
high O 0
concentrations O 0
it O 0
acts O 0
in O 0
an O 0
inhibitory O 0
fashion O 0
on O 0
the O 0
cytostatic O 0
action O 0
of O 0
the O 0
drug O 0
. O 0

Risk O 0
factors O 0
and O 0
predictors O 0
of O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesia B-Disease 0
among O 0
multiethnic O 0
Malaysians O 0
with O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

Chronic O 0
pulsatile O 0
levodopa B-Chemical 0
therapy O 0
for O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
( O 0
PD B-Disease 0
) O 0
leads O 0
to O 0
the O 0
development O 0
of O 0
motor O 0
fluctuations O 0
and O 0
dyskinesia B-Disease 0
. O 0

We O 0
studied O 0
the O 0
prevalence O 0
and O 0
predictors O 0
of O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesia B-Disease 0
among O 0
multiethnic O 0
Malaysian O 0
patients O 0
with O 0
PD B-Disease 0
. O 0

METHODS O 0
: O 0
This O 0
is O 0
a O 0
cross O 0
- O 0
sectional O 0
study O 0
involving O 0
95 O 0
patients O 0
with O 0
PD B-Disease 0
on O 0
uninterrupted O 0
levodopa B-Chemical 0
therapy O 0
for O 0
at O 0
least O 0
6 O 0
months O 0
. O 0

The O 0
instrument O 0
used O 0
was O 0
the O 0
UPDRS O 0
questionnaires O 0
. O 0

The O 0
predictors O 0
of O 0
dyskinesia B-Disease 0
were O 0
determined O 0
using O 0
multivariate O 0
logistic O 0
regression O 0
analysis O 0
. O 0

RESULTS O 0
: O 0
The O 0
mean O 0
age O 0
was O 0
65 O 0
. O 0
6 O 0
+ O 0
8 O 0
. O 0
5 O 0
years O 0
. O 0

The O 0
mean O 0
onset O 0
age O 0
was O 0
58 O 0
. O 0
5 O 0
+ O 0
9 O 0
. O 0
8 O 0
years O 0
. O 0

The O 0
median O 0
disease O 0
duration O 0
was O 0
6 O 0
( O 0
7 O 0
) O 0
years O 0
. O 0

Dyskinesia B-Disease 0
was O 0
present O 0
in O 0
44 O 0
% O 0
( O 0
n O 0
= O 0
42 O 0
) O 0
with O 0
median O 0
levodopa B-Chemical 0
therapy O 0
of O 0
3 O 0
years O 0
. O 0

There O 0
were O 0
64 O 0
. O 0
3 O 0
% O 0
Chinese O 0
, O 0
31 O 0
% O 0
Malays O 0
, O 0
and O 0
3 O 0
. O 0
7 O 0
% O 0
Indians O 0
and O 0
other O 0
ethnic O 0
groups O 0
. O 0

Eighty O 0
- O 0
one O 0
percent O 0
of O 0
patients O 0
with O 0
dyskinesia B-Disease 0
had O 0
clinical O 0
fluctuations O 0
. O 0

Patients O 0
with O 0
dyskinesia B-Disease 0
had O 0
lower O 0
onset O 0
age O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
longer O 0
duration O 0
of O 0
levodopa B-Chemical 0
therapy O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
longer O 0
disease O 0
duration O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
higher O 0
total O 0
daily O 0
levodopa B-Chemical 0
dose O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
and O 0
higher O 0
total O 0
UPDRS O 0
scores O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
005 O 0
) O 0
than O 0
patients O 0
without O 0
dyskinesia B-Disease 0
. O 0

The O 0
three O 0
significant O 0
predictors O 0
of O 0
dyskinesia B-Disease 0
were O 0
duration O 0
of O 0
levodopa B-Chemical 0
therapy O 0
, O 0
onset O 0
age O 0
, O 0
and O 0
total O 0
daily O 0
levodopa B-Chemical 0
dose O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
prevalence O 0
of O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesia B-Disease 0
in O 0
our O 0
patients O 0
was O 0
44 O 0
% O 0
. O 0

The O 0
most O 0
significant O 0
predictors O 0
were O 0
duration O 0
of O 0
levodopa B-Chemical 0
therapy O 0
, O 0
total O 0
daily O 0
levodopa B-Chemical 0
dose O 0
, O 0
and O 0
onset O 0
age O 0
. O 0

Dose O 0
- O 0
dependent O 0
neurotoxicity B-Disease 0
of O 0
high O 0
- O 0
dose O 0
busulfan B-Chemical 0
in O 0
children O 0
: O 0
a O 0
clinical O 0
and O 0
pharmacological O 0
study O 0
. O 0

Busulfan B-Chemical 0
is O 0
known O 0
to O 0
be O 0
neurotoxic B-Disease 0
in O 0
animals O 0
and O 0
humans O 0
, O 0
but O 0
its O 0
acute O 0
neurotoxicity B-Disease 0
remains O 0
poorly O 0
characterized O 0
in O 0
children O 0
. O 0

We O 0
report O 0
here O 0
a O 0
retrospective O 0
study O 0
of O 0
123 O 0
children O 0
( O 0
median O 0
age O 0
, O 0
6 O 0
. O 0
5 O 0
years O 0
) O 0
receiving O 0
high O 0
- O 0
dose O 0
busulfan B-Chemical 0
in O 0
combined O 0
chemotherapy O 0
before O 0
bone O 0
marrow O 0
transplantation O 0
for O 0
malignant O 0
solid O 0
tumors B-Disease 0
, O 0
brain B-Disease 0
tumors I-Disease 0
excluded O 0
. O 0

Busulfan B-Chemical 0
was O 0
given O 0
p O 0
. O 0
o O 0
. O 0
, O 0
every O 0
6 O 0
hours O 0
for O 0
16 O 0
doses O 0
over O 0
4 O 0
days O 0
. O 0

Two O 0
total O 0
doses O 0
were O 0
consecutively O 0
used O 0
: O 0
16 O 0
mg O 0
/ O 0
kg O 0
, O 0
then O 0
600 O 0
mg O 0
/ O 0
m2 O 0
. O 0

The O 0
dose O 0
calculation O 0
on O 0
the O 0
basis O 0
of O 0
body O 0
surface O 0
area O 0
results O 0
in O 0
higher O 0
doses O 0
in O 0
young O 0
children O 0
than O 0
in O 0
older O 0
patients O 0
( O 0
16 O 0
to O 0
28 O 0
mg O 0
/ O 0
kg O 0
) O 0
. O 0

Ninety O 0
- O 0
six O 0
patients O 0
were O 0
not O 0
given O 0
anticonvulsive O 0
prophylaxis O 0
; O 0
7 O 0
( O 0
7 O 0
. O 0
5 O 0
% O 0
) O 0
developed O 0
seizures B-Disease 0
during O 0
the O 0
4 O 0
days O 0
of O 0
the O 0
busulfan B-Chemical 0
course O 0
or O 0
within O 0
24 O 0
h O 0
after O 0
the O 0
last O 0
dosing O 0
. O 0

When O 0
the O 0
total O 0
busulfan B-Chemical 0
dose O 0
was O 0
taken O 0
into O 0
account O 0
, O 0
there O 0
was O 0
a O 0
significant O 0
difference O 0
in O 0
terms O 0
of O 0
neurotoxicity B-Disease 0
incidence O 0
among O 0
patients O 0
under O 0
16 O 0
mg O 0
/ O 0
kg O 0
( O 0
1 O 0
of O 0
57 O 0
, O 0
1 O 0
. O 0
7 O 0
% O 0
) O 0
and O 0
patients O 0
under O 0
600 O 0
mg O 0
/ O 0
m2 O 0
( O 0
6 O 0
of O 0
39 O 0
, O 0
15 O 0
. O 0
4 O 0
% O 0
) O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
02 O 0
) O 0
. O 0

Twenty O 0
- O 0
seven O 0
patients O 0
were O 0
given O 0
a O 0
600 O 0
- O 0
mg O 0
/ O 0
m2 O 0
busulfan B-Chemical 0
total O 0
dose O 0
with O 0
continuous O 0
i O 0
. O 0
v O 0
. O 0
infusion O 0
of O 0
clonazepam B-Chemical 0
; O 0
none O 0
had O 0
any O 0
neurological B-Disease 0
symptoms I-Disease 0
. O 0

Busulfan B-Chemical 0
levels O 0
were O 0
measured O 0
by O 0
a O 0
gas O 0
chromatographic O 0
- O 0
mass O 0
spectrometry O 0
assay O 0
in O 0
the O 0
plasma O 0
and O 0
cerebrospinal O 0
fluid O 0
of O 0
9 O 0
children O 0
without O 0
central B-Disease 0
nervous I-Disease 0
system I-Disease 0
disease I-Disease 0
under O 0
600 O 0
mg O 0
/ O 0
m2 O 0
busulfan B-Chemical 0
with O 0
clonazepam B-Chemical 0
: O 0
busulfan B-Chemical 0
cerebrospinal O 0
fluid O 0
: O 0
plasma O 0
ratio O 0
was O 0
1 O 0
. O 0
39 O 0
. O 0

This O 0
was O 0
significantly O 0
different O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
02 O 0
) O 0
from O 0
the O 0
cerebrospinal O 0
fluid O 0
: O 0
plasma O 0
ratio O 0
previously O 0
defined O 0
in O 0
children O 0
receiving O 0
a O 0
16 O 0
- O 0
mg O 0
/ O 0
kg O 0
total O 0
dose O 0
of O 0
busulfan B-Chemical 0
. O 0

This O 0
study O 0
shows O 0
that O 0
busulfan B-Chemical 0
neurotoxicity B-Disease 0
is O 0
dose O 0
- O 0
dependent O 0
in O 0
children O 0
and O 0
efficiently O 0
prevented O 0
by O 0
clonazepam B-Chemical 0
. O 0

A O 0
busulfan B-Chemical 0
dose O 0
calculated O 0
on O 0
the O 0
basis O 0
of O 0
body O 0
surface O 0
area O 0
, O 0
resulting O 0
in O 0
higher O 0
doses O 0
in O 0
young O 0
children O 0
, O 0
was O 0
followed O 0
by O 0
increased O 0
neurotoxicity B-Disease 0
, O 0
close O 0
to O 0
neurotoxicity B-Disease 0
incidence O 0
observed O 0
in O 0
adults O 0
. O 0

Since O 0
plasma O 0
pharmacokinetic O 0
studies O 0
showed O 0
a O 0
faster O 0
busulfan B-Chemical 0
clearance O 0
in O 0
children O 0
than O 0
in O 0
adults O 0
, O 0
this O 0
new O 0
dose O 0
may O 0
approximate O 0
more O 0
closely O 0
the O 0
adult O 0
systemic O 0
exposure O 0
obtained O 0
after O 0
the O 0
usual O 0
16 O 0
- O 0
mg O 0
/ O 0
kg O 0
total O 0
dose O 0
, O 0
with O 0
potential O 0
inferences O 0
in O 0
terms O 0
of O 0
anticancer O 0
or O 0
myeloablative O 0
effects O 0
. O 0

The O 0
busulfan B-Chemical 0
dose O 0
in O 0
children O 0
and O 0
infants O 0
undergoing O 0
bone O 0
marrow O 0
transplantation O 0
should O 0
be O 0
reconsidered O 0
on O 0
the O 0
basis O 0
of O 0
pharmacokinetic O 0
studies O 0
. O 0

An O 0
unexpected O 0
diagnosis O 0
in O 0
a O 0
renal O 0
- O 0
transplant O 0
patient O 0
with O 0
proteinuria B-Disease 0
treated O 0
with O 0
everolimus B-Chemical 0
: O 0
AL B-Disease 0
amyloidosis B-Disease 0
. O 0

Proteinuria B-Disease 0
is O 0
an O 0
expected O 0
complication O 0
in O 0
transplant O 0
patients O 0
treated O 0
with O 0
mammalian O 0
target O 0
of O 0
rapamycin B-Chemical 0
inhibitors O 0
( O 0
mTOR O 0
- O 0
i O 0
) O 0
. O 0

However O 0
, O 0
clinical O 0
suspicion O 0
should O 0
always O 0
be O 0
supported O 0
by O 0
histological O 0
evidence O 0
in O 0
order O 0
to O 0
investigate O 0
potential O 0
alternate O 0
diagnoses O 0
such O 0
as O 0
acute O 0
or O 0
chronic O 0
rejection O 0
, O 0
interstitial O 0
fibrosis B-Disease 0
and O 0
tubular O 0
atrophy B-Disease 0
, O 0
or O 0
recurrent O 0
or O 0
de O 0
novo O 0
glomerulopathy B-Disease 0
. O 0

In O 0
this O 0
case O 0
we O 0
report O 0
the O 0
unexpected O 0
diagnosis O 0
of O 0
amyloidosis B-Disease 0
in O 0
a O 0
renal O 0
- O 0
transplant O 0
patient O 0
with O 0
pre O 0
- O 0
transplant O 0
monoclonal O 0
gammapathy O 0
of O 0
undetermined O 0
significance O 0
who O 0
developed O 0
proteinuria B-Disease 0
after O 0
conversion O 0
from O 0
tacrolimus B-Chemical 0
to O 0
everolimus B-Chemical 0
. O 0

Long O 0
- O 0
term O 0
oral O 0
galactose B-Chemical 0
treatment O 0
prevents O 0
cognitive B-Disease 0
deficits I-Disease 0
in O 0
male O 0
Wistar O 0
rats O 0
treated O 0
intracerebroventricularly O 0
with O 0
streptozotocin B-Chemical 0
. O 0

Basic O 0
and O 0
clinical O 0
research O 0
has O 0
demonstrated O 0
that O 0
dementia B-Disease 0
of O 0
sporadic O 0
Alzheimer B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
( O 0
sAD O 0
) O 0
type O 0
is O 0
associated O 0
with O 0
dysfunction O 0
of O 0
the O 0
insulin O 0
- O 0
receptor O 0
( O 0
IR O 0
) O 0
system O 0
followed O 0
by O 0
decreased O 0
glucose B-Chemical 0
transport O 0
via O 0
glucose B-Chemical 0
transporter O 0
GLUT4 O 0
and O 0
decreased O 0
glucose B-Chemical 0
metabolism O 0
in O 0
brain O 0
cells O 0
. O 0

An O 0
alternative O 0
source O 0
of O 0
energy O 0
is O 0
d B-Chemical 0
- I-Chemical 0
galactose I-Chemical 0
( O 0
the O 0
C O 0
- O 0
4 O 0
- O 0
epimer O 0
of O 0
d B-Chemical 0
- I-Chemical 0
glucose I-Chemical 0
) O 0
which O 0
is O 0
transported O 0
into O 0
the O 0
brain O 0
by O 0
insulin O 0
- O 0
independent O 0
GLUT3 O 0
transporter O 0
where O 0
it O 0
might O 0
be O 0
metabolized O 0
to O 0
glucose B-Chemical 0
via O 0
the O 0
Leloir O 0
pathway O 0
. O 0

Exclusively O 0
parenteral O 0
daily O 0
injections O 0
of O 0
galactose B-Chemical 0
induce O 0
memory B-Disease 0
deterioration I-Disease 0
in O 0
rodents O 0
and O 0
are O 0
used O 0
to O 0
generate O 0
animal O 0
aging O 0
model O 0
, O 0
but O 0
the O 0
effects O 0
of O 0
oral O 0
galactose B-Chemical 0
treatment O 0
on O 0
cognitive O 0
functions O 0
have O 0
never O 0
been O 0
tested O 0
. O 0

We O 0
have O 0
investigated O 0
the O 0
effects O 0
of O 0
continuous O 0
daily O 0
oral O 0
galactose B-Chemical 0
( O 0
200 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
) O 0
treatment O 0
on O 0
cognitive B-Disease 0
deficits I-Disease 0
in O 0
streptozotocin B-Chemical 0
- O 0
induced O 0
( O 0
STZ B-Chemical 0
- O 0
icv O 0
) O 0
rat O 0
model O 0
of O 0
sAD O 0
, O 0
tested O 0
by O 0
Morris O 0
Water O 0
Maze O 0
and O 0
Passive O 0
Avoidance O 0
test O 0
, O 0
respectively O 0
. O 0

One O 0
month O 0
of O 0
oral O 0
galactose B-Chemical 0
treatment O 0
initiated O 0
immediately O 0
after O 0
the O 0
STZ B-Chemical 0
- O 0
icv O 0
administration O 0
, O 0
successfully O 0
prevented O 0
development O 0
of O 0
the O 0
STZ B-Chemical 0
- O 0
icv O 0
- O 0
induced O 0
cognitive B-Disease 0
deficits I-Disease 0
. O 0

Beneficial O 0
effect O 0
of O 0
oral O 0
galactose B-Chemical 0
was O 0
independent O 0
of O 0
the O 0
rat O 0
age O 0
and O 0
of O 0
the O 0
galactose B-Chemical 0
dose O 0
ranging O 0
from O 0
100 O 0
to O 0
300 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
. O 0

Additionally O 0
, O 0
oral O 0
galactose B-Chemical 0
administration O 0
led O 0
to O 0
the O 0
appearance O 0
of O 0
galactose B-Chemical 0
in O 0
the O 0
blood O 0
. O 0

The O 0
increase O 0
of O 0
galactose B-Chemical 0
concentration O 0
in O 0
the O 0
cerebrospinal O 0
fluid O 0
was O 0
several O 0
times O 0
lower O 0
after O 0
oral O 0
than O 0
after O 0
parenteral O 0
administration O 0
of O 0
the O 0
same O 0
galactose B-Chemical 0
dose O 0
. O 0

Oral O 0
galactose B-Chemical 0
exposure O 0
might O 0
have O 0
beneficial O 0
effects O 0
on O 0
learning O 0
and O 0
memory O 0
ability O 0
and O 0
could O 0
be O 0
worth O 0
investigating O 0
for O 0
improvement O 0
of O 0
cognitive B-Disease 0
deficits I-Disease 0
associated O 0
with O 0
glucose B-Disease 0
hypometabolism I-Disease 0
in O 0
AD B-Disease 0
. O 0

An O 0
investigation O 0
of O 0
the O 0
pattern O 0
of O 0
kidney B-Disease 0
injury I-Disease 0
in O 0
HIV O 0
- O 0
positive O 0
persons O 0
exposed O 0
to O 0
tenofovir B-Chemical 0
disoproxil I-Chemical 0
fumarate I-Chemical 0
: O 0
an O 0
examination O 0
of O 0
a O 0
large O 0
population O 0
database O 0
( O 0
MHRA O 0
database O 0
) O 0
. O 0

The O 0
potential O 0
for O 0
tenofovir B-Chemical 0
to O 0
cause O 0
a O 0
range O 0
of O 0
kidney O 0
syndromes O 0
has O 0
been O 0
established O 0
from O 0
mechanistic O 0
and O 0
randomised O 0
clinical O 0
trials O 0
. O 0

However O 0
, O 0
the O 0
exact O 0
pattern O 0
of O 0
kidney O 0
involvement O 0
is O 0
still O 0
uncertain O 0
. O 0

We O 0
undertook O 0
a O 0
descriptive O 0
analysis O 0
of O 0
Yellow O 0
Card O 0
records O 0
of O 0
407 O 0
HIV O 0
- O 0
positive O 0
persons O 0
taking O 0
tenofovir B-Chemical 0
disoproxil I-Chemical 0
fumarate I-Chemical 0
( O 0
TDF B-Chemical 0
) O 0
as O 0
part O 0
of O 0
their O 0
antiretroviral O 0
therapy O 0
regimen O 0
and O 0
submitted O 0
to O 0
the O 0
Medicines O 0
and O 0
Healthcare O 0
Products O 0
Regulatory O 0
Agency O 0
( O 0
MHRA O 0
) O 0
with O 0
suspected O 0
kidney O 0
adverse O 0
effects O 0
. O 0

Reports O 0
that O 0
satisfy O 0
defined O 0
criteria O 0
were O 0
classified O 0
as O 0
acute B-Disease 0
kidney I-Disease 0
injury I-Disease 0
, O 0
kidney B-Disease 0
tubular I-Disease 0
dysfunction I-Disease 0
and O 0
Fanconi B-Disease 0
syndrome I-Disease 0
. O 0

Of O 0
the O 0
407 O 0
Yellow O 0
Card O 0
records O 0
analysed O 0
, O 0
106 O 0
satisfied O 0
criteria O 0
for O 0
TDF B-Chemical 0
- O 0
related O 0
kidney B-Disease 0
disease I-Disease 0
, O 0
of O 0
which O 0
53 O 0
( O 0
50 O 0
% O 0
) O 0
had O 0
features O 0
of O 0
kidney B-Disease 0
tubular I-Disease 0
dysfunction I-Disease 0
, O 0
35 O 0
( O 0
33 O 0
% O 0
) O 0
were O 0
found O 0
to O 0
have O 0
features O 0
of O 0
glomerular B-Disease 0
dysfunction I-Disease 0
and O 0
18 O 0
( O 0
17 O 0
% O 0
) O 0
had O 0
Fanconi B-Disease 0
syndrome I-Disease 0
. O 0

The O 0
median O 0
TDF B-Chemical 0
exposure O 0
was O 0
316 O 0
days O 0
( O 0
interquartile O 0
range O 0
120 O 0
- O 0
740 O 0
) O 0
. O 0

The O 0
incidence O 0
of O 0
hospitalisation O 0
for O 0
TDF B-Chemical 0
kidney O 0
adverse O 0
effects O 0
was O 0
high O 0
, O 0
particularly O 0
amongst O 0
patients O 0
with O 0
features O 0
of O 0
Fanconi B-Disease 0
syndrome I-Disease 0
. O 0

The O 0
pattern O 0
of O 0
kidney O 0
syndromes O 0
in O 0
this O 0
population O 0
series O 0
mirrors O 0
that O 0
reported O 0
in O 0
randomised O 0
clinical O 0
trials O 0
. O 0

Cessation O 0
of O 0
TDF B-Chemical 0
was O 0
associated O 0
with O 0
complete O 0
restoration O 0
of O 0
kidney O 0
function O 0
in O 0
up O 0
half O 0
of O 0
the O 0
patients O 0
in O 0
this O 0
report O 0
. O 0

Incidence O 0
of O 0
postoperative B-Disease 0
delirium I-Disease 0
is O 0
high O 0
even O 0
in O 0
a O 0
population O 0
without O 0
known O 0
risk O 0
factors O 0
. O 0

PURPOSE O 0
: O 0
Postoperative B-Disease 0
delirium I-Disease 0
is O 0
a O 0
recognized O 0
complication O 0
in O 0
populations O 0
at O 0
risk O 0
. O 0

The O 0
aim O 0
of O 0
this O 0
study O 0
is O 0
to O 0
assess O 0
the O 0
prevalence O 0
of O 0
early O 0
postoperative B-Disease 0
delirium I-Disease 0
in O 0
a O 0
population O 0
without O 0
known O 0
risk O 0
factors O 0
admitted O 0
to O 0
the O 0
ICU O 0
for O 0
postoperative O 0
monitoring O 0
after O 0
elective O 0
major O 0
surgery O 0
. O 0

The O 0
secondary O 0
outcome O 0
investigated O 0
is O 0
to O 0
identify O 0
eventual O 0
independent O 0
risk O 0
factors O 0
among O 0
demographic O 0
data O 0
and O 0
anesthetic O 0
drugs O 0
used O 0
. O 0

METHODS O 0
: O 0
An O 0
observational O 0
, O 0
prospective O 0
study O 0
was O 0
conducted O 0
on O 0
a O 0
consecutive O 0
cohort O 0
of O 0
patients O 0
admitted O 0
to O 0
our O 0
ICU O 0
within O 0
and O 0
for O 0
at O 0
least O 0
24 O 0
h O 0
after O 0
major O 0
surgical O 0
procedures O 0
. O 0

Exclusion O 0
criteria O 0
were O 0
any O 0
preexisting O 0
predisposing O 0
factor O 0
for O 0
delirium B-Disease 0
or O 0
other O 0
potentially O 0
confounding O 0
neurological B-Disease 0
dysfunctions I-Disease 0
. O 0

Patients O 0
were O 0
assessed O 0
daily O 0
using O 0
the O 0
confusion B-Disease 0
assessment O 0
method O 0
for O 0
the O 0
ICU O 0
scale O 0
for O 0
3 O 0
days O 0
after O 0
the O 0
surgical O 0
procedure O 0
. O 0

Early O 0
postoperative B-Disease 0
delirium I-Disease 0
incidence O 0
risk O 0
factors O 0
were O 0
then O 0
assessed O 0
through O 0
three O 0
different O 0
multiple O 0
regression O 0
models O 0
. O 0

RESULTS O 0
: O 0
According O 0
to O 0
the O 0
confusion O 0
assessment O 0
method O 0
for O 0
the O 0
ICU O 0
scale O 0
, O 0
28 O 0
% O 0
of O 0
patients O 0
were O 0
diagnosed O 0
with O 0
early O 0
postoperative B-Disease 0
delirium I-Disease 0
. O 0

The O 0
use O 0
of O 0
thiopentone B-Chemical 0
was O 0
significantly O 0
associated O 0
with O 0
an O 0
eight O 0
- O 0
fold O 0
- O 0
higher O 0
risk O 0
for O 0
delirium B-Disease 0
compared O 0
to O 0
propofol B-Chemical 0
( O 0
57 O 0
. O 0
1 O 0
% O 0
vs O 0
. O 0
7 O 0
. O 0
1 O 0
% O 0
, O 0
RR O 0
= O 0
8 O 0
. O 0
0 O 0
, O 0
X2 O 0
= O 0
4 O 0
. O 0
256 O 0
; O 0
df O 0
= O 0
1 O 0
; O 0
0 O 0
. O 0
05 O 0
< O 0
p O 0
< O 0
0 O 0
. O 0
02 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
In O 0
this O 0
study O 0
early O 0
postoperative B-Disease 0
delirium I-Disease 0
was O 0
found O 0
to O 0
be O 0
a O 0
very O 0
common O 0
complication O 0
after O 0
major O 0
surgery O 0
, O 0
even O 0
in O 0
a O 0
population O 0
without O 0
known O 0
risk O 0
factors O 0
. O 0

Thiopentone B-Chemical 0
was O 0
independently O 0
associated O 0
with O 0
an O 0
increase O 0
in O 0
its O 0
relative O 0
risk O 0
. O 0

A O 0
single O 0
neurotoxic B-Disease 0
dose O 0
of O 0
methamphetamine B-Chemical 0
induces O 0
a O 0
long O 0
- O 0
lasting O 0
depressive B-Disease 0
- O 0
like O 0
behaviour O 0
in O 0
mice O 0
. O 0

Methamphetamine B-Chemical 0
( O 0
METH B-Chemical 0
) O 0
triggers O 0
a O 0
disruption O 0
of O 0
the O 0
monoaminergic O 0
system O 0
and O 0
METH B-Chemical 0
abuse O 0
leads O 0
to O 0
negative O 0
emotional O 0
states O 0
including O 0
depressive B-Disease 0
symptoms I-Disease 0
during O 0
drug O 0
withdrawal O 0
. O 0

However O 0
, O 0
it O 0
is O 0
currently O 0
unknown O 0
if O 0
the O 0
acute O 0
toxic O 0
dosage O 0
of O 0
METH B-Chemical 0
also O 0
causes O 0
a O 0
long O 0
- O 0
lasting O 0
depressive B-Disease 0
phenotype O 0
and O 0
persistent O 0
monoaminergic O 0
deficits O 0
. O 0

Thus O 0
, O 0
we O 0
now O 0
assessed O 0
the O 0
depressive B-Disease 0
- O 0
like O 0
behaviour O 0
in O 0
mice O 0
at O 0
early O 0
and O 0
long O 0
- O 0
term O 0
periods O 0
following O 0
a O 0
single O 0
high O 0
METH B-Chemical 0
dose O 0
( O 0
30 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

METH B-Chemical 0
did O 0
not O 0
alter O 0
the O 0
motor O 0
function O 0
and O 0
procedural O 0
memory O 0
of O 0
mice O 0
as O 0
assessed O 0
by O 0
swimming O 0
speed O 0
and O 0
escape O 0
latency O 0
to O 0
find O 0
the O 0
platform O 0
in O 0
a O 0
cued O 0
version O 0
of O 0
the O 0
water O 0
maze O 0
task O 0
. O 0

However O 0
, O 0
METH B-Chemical 0
significantly O 0
increased O 0
the O 0
immobility O 0
time O 0
in O 0
the O 0
tail O 0
suspension O 0
test O 0
at O 0
3 O 0
and O 0
49 O 0
days O 0
post O 0
- O 0
administration O 0
. O 0

This O 0
depressive B-Disease 0
- O 0
like O 0
profile O 0
induced O 0
by O 0
METH B-Chemical 0
was O 0
accompanied O 0
by O 0
a O 0
marked O 0
depletion O 0
of O 0
frontostriatal O 0
dopaminergic O 0
and O 0
serotonergic O 0
neurotransmission O 0
, O 0
indicated O 0
by O 0
a O 0
reduction O 0
in O 0
the O 0
levels O 0
of O 0
dopamine B-Chemical 0
, O 0
DOPAC B-Chemical 0
and O 0
HVA B-Chemical 0
, O 0
tyrosine B-Chemical 0
hydroxylase O 0
and O 0
serotonin B-Chemical 0
, O 0
observed O 0
at O 0
both O 0
3 O 0
and O 0
49 O 0
days O 0
post O 0
- O 0
administration O 0
. O 0

In O 0
parallel O 0
, O 0
another O 0
neurochemical O 0
feature O 0
of O 0
depression B-Disease 0
- O 0
- O 0
astroglial O 0
dysfunction O 0
- O 0
- O 0
was O 0
unaffected O 0
in O 0
the O 0
cortex O 0
and O 0
the O 0
striatal O 0
levels O 0
of O 0
the O 0
astrocytic O 0
protein O 0
marker O 0
, O 0
glial O 0
fibrillary O 0
acidic O 0
protein O 0
, O 0
were O 0
only O 0
transiently O 0
increased O 0
at O 0
3 O 0
days O 0
. O 0

These O 0
findings O 0
demonstrate O 0
for O 0
the O 0
first O 0
time O 0
that O 0
a O 0
single O 0
high O 0
dose O 0
of O 0
METH B-Chemical 0
induces O 0
long O 0
- O 0
lasting O 0
depressive B-Disease 0
- O 0
like O 0
behaviour O 0
in O 0
mice O 0
associated O 0
with O 0
a O 0
persistent O 0
disruption O 0
of O 0
frontostriatal O 0
dopaminergic O 0
and O 0
serotonergic O 0
homoeostasis O 0
. O 0

Linezolid B-Chemical 0
- O 0
induced O 0
optic B-Disease 0
neuropathy I-Disease 0
. O 0

Many O 0
systemic O 0
antimicrobials O 0
have O 0
been O 0
implicated O 0
to O 0
cause O 0
ocular O 0
adverse O 0
effects O 0
. O 0

This O 0
is O 0
especially O 0
relevant O 0
in O 0
multidrug O 0
therapy O 0
where O 0
more O 0
than O 0
one O 0
drug O 0
can O 0
cause O 0
a O 0
similar O 0
ocular O 0
adverse O 0
effect O 0
. O 0

We O 0
describe O 0
a O 0
case O 0
of O 0
progressive O 0
loss B-Disease 0
of I-Disease 0
vision I-Disease 0
associated O 0
with O 0
linezolid B-Chemical 0
therapy O 0
. O 0

A O 0
45 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
patient O 0
who O 0
was O 0
on O 0
treatment O 0
with O 0
multiple O 0
second O 0
- O 0
line O 0
anti O 0
- O 0
tuberculous O 0
drugs O 0
including O 0
linezolid B-Chemical 0
and O 0
ethambutol B-Chemical 0
for O 0
extensively B-Disease 0
drug I-Disease 0
- I-Disease 0
resistant I-Disease 0
tuberculosis I-Disease 0
( O 0
XDR B-Disease 0
- I-Disease 0
TB I-Disease 0
) O 0
presented O 0
to O 0
us O 0
with O 0
painless O 0
progressive O 0
loss B-Disease 0
of I-Disease 0
vision I-Disease 0
in O 0
both O 0
eyes O 0
. O 0

Color O 0
vision O 0
was O 0
defective O 0
and O 0
fundus O 0
examination O 0
revealed O 0
optic B-Disease 0
disc I-Disease 0
edema I-Disease 0
in O 0
both O 0
eyes O 0
. O 0

Ethambutol B-Chemical 0
- O 0
induced O 0
toxic B-Disease 0
optic I-Disease 0
neuropathy I-Disease 0
was O 0
suspected O 0
and O 0
tablet O 0
ethambutol B-Chemical 0
was O 0
withdrawn O 0
. O 0

Deterioration B-Disease 0
of I-Disease 0
vision I-Disease 0
occurred O 0
despite O 0
withdrawal O 0
of O 0
ethambutol B-Chemical 0
. O 0

Discontinuation O 0
of O 0
linezolid B-Chemical 0
resulted O 0
in O 0
marked O 0
improvement O 0
of O 0
vision O 0
. O 0

Our O 0
report O 0
emphasizes O 0
the O 0
need O 0
for O 0
monitoring O 0
of O 0
visual O 0
function O 0
in O 0
patients O 0
on O 0
long O 0
- O 0
term O 0
linezolid B-Chemical 0
treatment O 0
. O 0

Resuscitation O 0
with O 0
lipid O 0
, O 0
epinephrine B-Chemical 0
, O 0
or O 0
both O 0
in O 0
levobupivacaine B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
toxicity I-Disease 0
in O 0
newborn O 0
piglets O 0
. O 0

BACKGROUND O 0
: O 0
The O 0
optimal O 0
dosing O 0
regimens O 0
of O 0
lipid O 0
emulsion O 0
, O 0
epinephrine B-Chemical 0
, O 0
or O 0
both O 0
are O 0
not O 0
yet O 0
determined O 0
in O 0
neonates O 0
in O 0
cases O 0
of O 0
local O 0
anaesthetic O 0
systemic O 0
toxicity B-Disease 0
( O 0
LAST O 0
) O 0
. O 0

METHODS O 0
: O 0
Newborn O 0
piglets O 0
received O 0
levobupivacaine B-Chemical 0
until O 0
cardiovascular B-Disease 0
collapse I-Disease 0
occurred O 0
. O 0

Standard O 0
cardiopulmonary O 0
resuscitation O 0
was O 0
started O 0
and O 0
electrocardiogram O 0
( O 0
ECG O 0
) O 0
was O 0
monitored O 0
for O 0
ventricular B-Disease 0
tachycardia I-Disease 0
, O 0
fibrillation B-Disease 0
, O 0
or O 0
QRS O 0
prolongation O 0
. O 0

Piglets O 0
were O 0
then O 0
randomly O 0
allocated O 0
to O 0
four O 0
groups O 0
: O 0
control O 0
( O 0
saline O 0
) O 0
, O 0
Intralipid O 0
( O 0
) O 0
alone O 0
, O 0
epinephrine B-Chemical 0
alone O 0
, O 0
or O 0
a O 0
combination O 0
of O 0
Intralipd O 0
plus O 0
epinephrine B-Chemical 0
. O 0

Resuscitation O 0
continued O 0
for O 0
30 O 0
min O 0
or O 0
until O 0
there O 0
was O 0
a O 0
return O 0
of O 0
spontaneous O 0
circulation O 0
( O 0
ROSC O 0
) O 0
accompanied O 0
by O 0
a O 0
mean O 0
arterial O 0
pressure O 0
at O 0
or O 0
superior O 0
to O 0
the O 0
baseline O 0
pressure O 0
and O 0
normal O 0
sinus O 0
rhythm O 0
for O 0
a O 0
period O 0
of O 0
30 O 0
min O 0
. O 0

RESULTS O 0
: O 0
ROSC O 0
was O 0
achieved O 0
in O 0
only O 0
one O 0
of O 0
the O 0
control O 0
piglets O 0
compared O 0
with O 0
most O 0
of O 0
the O 0
treated O 0
piglets O 0
. O 0

Mortality O 0
was O 0
not O 0
significantly O 0
different O 0
between O 0
the O 0
three O 0
treatment O 0
groups O 0
, O 0
but O 0
was O 0
significantly O 0
lower O 0
in O 0
all O 0
the O 0
treatment O 0
groups O 0
compared O 0
with O 0
control O 0
. O 0

The O 0
number O 0
of O 0
ECG O 0
abnormalities O 0
was O 0
zero O 0
in O 0
the O 0
Intralipid O 0
only O 0
group O 0
, O 0
but O 0
14 O 0
and O 0
17 O 0
, O 0
respectively O 0
, O 0
in O 0
the O 0
epinephrine B-Chemical 0
and O 0
epinephrine B-Chemical 0
plus O 0
lipid O 0
groups O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Lipid O 0
emulsion O 0
with O 0
or O 0
without O 0
epinephrine B-Chemical 0
, O 0
or O 0
epinephrine B-Chemical 0
alone O 0
were O 0
equally O 0
effective O 0
in O 0
achieving O 0
a O 0
return O 0
to O 0
spontaneous O 0
circulation O 0
in O 0
this O 0
model O 0
of O 0
LAST O 0
. O 0

Epinephrine B-Chemical 0
alone O 0
or O 0
in O 0
combination O 0
with O 0
lipid O 0
was O 0
associated O 0
with O 0
an O 0
increased O 0
number O 0
of O 0
ECG O 0
abnormalities O 0
compared O 0
with O 0
lipid O 0
emulsion O 0
alone O 0
. O 0

Incidence O 0
of O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
type I-Disease 0
II I-Disease 0
and O 0
postoperative O 0
recovery O 0
of O 0
platelet O 0
count O 0
in O 0
liver O 0
graft O 0
recipients O 0
: O 0
a O 0
retrospective O 0
cohort O 0
analysis O 0
. O 0

BACKGROUND O 0
: O 0
Thrombocytopenia B-Disease 0
in O 0
patients O 0
with O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
liver I-Disease 0
disease I-Disease 0
is O 0
a O 0
common O 0
disorder O 0
caused O 0
mainly O 0
by O 0
portal B-Disease 0
hypertension I-Disease 0
, O 0
low O 0
levels O 0
of O 0
thrombopoetin O 0
, O 0
and O 0
endotoxemia B-Disease 0
. O 0

The O 0
impact O 0
of O 0
immune O 0
- O 0
mediated O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
type I-Disease 0
II I-Disease 0
( O 0
HIT B-Disease 0
type I-Disease 0
II I-Disease 0
) O 0
as O 0
a O 0
cause O 0
of O 0
thrombocytopenia B-Disease 0
after O 0
liver O 0
transplantation O 0
is O 0
not O 0
yet O 0
understood O 0
, O 0
with O 0
few O 0
literature O 0
citations O 0
reporting O 0
contradictory O 0
results O 0
. O 0

The O 0
aim O 0
of O 0
our O 0
study O 0
was O 0
to O 0
demonstrate O 0
the O 0
perioperative O 0
course O 0
of O 0
thrombocytopenia B-Disease 0
after O 0
liver O 0
transplantation O 0
and O 0
determine O 0
the O 0
occurrence O 0
of O 0
clinical O 0
HIT B-Disease 0
type I-Disease 0
II I-Disease 0
. O 0

METHOD O 0
: O 0
We O 0
retrospectively O 0
evaluated O 0
the O 0
medical O 0
records O 0
of O 0
205 O 0
consecutive O 0
adult O 0
patients O 0
who O 0
underwent O 0
full O 0
- O 0
size O 0
liver O 0
transplantation O 0
between O 0
January O 0
2006 O 0
and O 0
December O 0
2010 O 0
due O 0
to O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
or I-Disease 0
malignant I-Disease 0
liver I-Disease 0
disease I-Disease 0
. O 0

Preoperative O 0
platelet O 0
count O 0
, O 0
postoperative O 0
course O 0
of O 0
platelets O 0
, O 0
and O 0
clinical O 0
signs O 0
of O 0
HIT B-Disease 0
type I-Disease 0
II I-Disease 0
were O 0
analyzed O 0
. O 0

RESULTS O 0
: O 0
A O 0
total O 0
of O 0
155 O 0
( O 0
75 O 0
. O 0
6 O 0
% O 0
) O 0
of O 0
205 O 0
patients O 0
had O 0
thrombocytopenia B-Disease 0
before O 0
transplantation O 0
, O 0
significantly O 0
influenced O 0
by O 0
Model O 0
of O 0
End B-Disease 0
- I-Disease 0
Stage I-Disease 0
Liver I-Disease 0
Disease I-Disease 0
score O 0
and O 0
liver B-Disease 0
cirrhosis I-Disease 0
. O 0

The O 0
platelet O 0
count O 0
exceeded O 0
100 O 0
, O 0
000 O 0
/ O 0
uL O 0
in O 0
most O 0
of O 0
the O 0
patients O 0
( O 0
n O 0
= O 0
193 O 0
) O 0
at O 0
a O 0
medium O 0
of O 0
7 O 0
d O 0
. O 0

Regarding O 0
HIT B-Disease 0
II I-Disease 0
, O 0
there O 0
were O 0
four O 0
( O 0
1 O 0
. O 0
95 O 0
% O 0
) O 0
patients O 0
with O 0
a O 0
background O 0
of O 0
HIT B-Disease 0
type I-Disease 0
II I-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
incidence O 0
of O 0
HIT B-Disease 0
in O 0
patients O 0
with O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
hepatic I-Disease 0
failure I-Disease 0
is O 0
, O 0
with O 0
about O 0
1 O 0
. O 0
95 O 0
% O 0
, O 0
rare O 0
. O 0

For O 0
further O 0
reduction O 0
of O 0
HIT B-Disease 0
type I-Disease 0
II I-Disease 0
, O 0
the O 0
use O 0
of O 0
intravenous O 0
heparin B-Chemical 0
should O 0
be O 0
avoided O 0
and O 0
the O 0
prophylactic O 0
anticoagulation O 0
should O 0
be O 0
performed O 0
with O 0
low O 0
- O 0
molecular O 0
- O 0
weight O 0
heparin B-Chemical 0
after O 0
normalization O 0
of O 0
platelet O 0
count O 0
. O 0

Takotsubo B-Disease 0
syndrome I-Disease 0
( O 0
or O 0
apical B-Disease 0
ballooning I-Disease 0
syndrome I-Disease 0
) O 0
secondary O 0
to O 0
Zolmitriptan B-Chemical 0
. O 0

Takotsubo B-Disease 0
syndrome I-Disease 0
( O 0
TS B-Disease 0
) O 0
, O 0
also O 0
known O 0
as O 0
broken B-Disease 0
heart I-Disease 0
syndrome I-Disease 0
, O 0
is O 0
characterized O 0
by O 0
left O 0
ventricle O 0
apical O 0
ballooning O 0
with O 0
elevated O 0
cardiac O 0
biomarkers O 0
and O 0
electrocardiographic O 0
changes O 0
suggestive O 0
of O 0
an O 0
acute B-Disease 0
coronary I-Disease 0
syndrome I-Disease 0
( O 0
ie O 0
, O 0
ST O 0
- O 0
segment O 0
elevation O 0
, O 0
T O 0
wave O 0
inversions O 0
, O 0
and O 0
pathologic O 0
Q O 0
waves O 0
) O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
54 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
medical O 0
history O 0
of O 0
mitral B-Disease 0
valve I-Disease 0
prolapse I-Disease 0
and O 0
migraines B-Disease 0
, O 0
who O 0
was O 0
admitted O 0
to O 0
the O 0
hospital O 0
for O 0
substernal O 0
chest B-Disease 0
pain I-Disease 0
and O 0
electrocardiogram O 0
demonstrated O 0
1 O 0
/ O 0
2 O 0
mm O 0
ST O 0
- O 0
segment O 0
elevation O 0
in O 0
leads O 0
II O 0
, O 0
III O 0
, O 0
aVF O 0
, O 0
V5 O 0
, O 0
and O 0
V6 O 0
and O 0
positive O 0
troponin O 0
I O 0
. O 0

Emergent O 0
coronary O 0
angiogram O 0
revealed O 0
normal O 0
coronary O 0
arteries O 0
with O 0
moderately O 0
reduced O 0
left O 0
ventricular O 0
ejection O 0
fraction O 0
with O 0
wall O 0
motion O 0
abnormalities O 0
consistent O 0
with O 0
TS B-Disease 0
. O 0

Detailed O 0
history O 0
obtained O 0
retrospectively O 0
revealed O 0
that O 0
the O 0
patient O 0
took O 0
zolmitriptan B-Chemical 0
sparingly O 0
only O 0
when O 0
she O 0
had O 0
migraines B-Disease 0
. O 0

But O 0
before O 0
this O 0
event O 0
, O 0
she O 0
was O 0
taking O 0
zolmitriptan B-Chemical 0
2 O 0
- O 0
3 O 0
times O 0
daily O 0
for O 0
several O 0
days O 0
because O 0
of O 0
a O 0
persistent O 0
migraine B-Disease 0
headache I-Disease 0
. O 0

She O 0
otherwise O 0
reported O 0
that O 0
she O 0
is O 0
quite O 0
active O 0
, O 0
rides O 0
horses O 0
, O 0
and O 0
does O 0
show O 0
jumping O 0
without O 0
any O 0
limitations O 0
in O 0
her O 0
physical O 0
activity O 0
. O 0

There O 0
was O 0
no O 0
evidence O 0
of O 0
any O 0
recent O 0
stress O 0
or O 0
status B-Disease 0
migrainosus I-Disease 0
. O 0

Extensive O 0
literature O 0
search O 0
revealed O 0
multiple O 0
cases O 0
of O 0
coronary B-Disease 0
artery I-Disease 0
vasospasm I-Disease 0
secondary O 0
to O 0
zolmitriptan B-Chemical 0
, O 0
but O 0
none O 0
of O 0
the O 0
cases O 0
were O 0
associated O 0
with O 0
TS B-Disease 0
. O 0

Depression B-Disease 0
, O 0
impulsiveness B-Disease 0
, O 0
sleep O 0
, O 0
and O 0
memory O 0
in O 0
past O 0
and O 0
present O 0
polydrug O 0
users O 0
of O 0
3 B-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
methylenedioxymethamphetamine I-Chemical 0
( O 0
MDMA B-Chemical 0
, O 0
ecstasy B-Chemical 0
) O 0
. O 0

RATIONALE O 0
: O 0
Ecstasy B-Chemical 0
( O 0
3 B-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
methylenedioxymethamphetamine I-Chemical 0
, O 0
MDMA B-Chemical 0
) O 0
is O 0
a O 0
worldwide O 0
recreational O 0
drug O 0
of O 0
abuse O 0
. O 0

Unfortunately O 0
, O 0
the O 0
results O 0
from O 0
human O 0
research O 0
investigating O 0
its O 0
psychological O 0
effects O 0
have O 0
been O 0
inconsistent O 0
. O 0

OBJECTIVES O 0
: O 0
The O 0
present O 0
study O 0
aimed O 0
to O 0
be O 0
the O 0
largest O 0
to O 0
date O 0
in O 0
sample O 0
size O 0
and O 0
5HT O 0
- O 0
related O 0
behaviors O 0
; O 0
the O 0
first O 0
to O 0
compare O 0
present O 0
ecstasy B-Chemical 0
users O 0
with O 0
past O 0
users O 0
after O 0
an O 0
abstinence O 0
of O 0
4 O 0
or O 0
more O 0
years O 0
, O 0
and O 0
the O 0
first O 0
to O 0
include O 0
robust O 0
controls O 0
for O 0
other O 0
recreational O 0
substances O 0
. O 0

METHODS O 0
: O 0
A O 0
sample O 0
of O 0
997 O 0
participants O 0
( O 0
52 O 0
% O 0
male O 0
) O 0
was O 0
recruited O 0
to O 0
four O 0
control O 0
groups O 0
( O 0
non O 0
- O 0
drug O 0
( O 0
ND O 0
) O 0
, O 0
alcohol B-Chemical 0
/ O 0
nicotine B-Chemical 0
( O 0
AN B-Chemical 0
) O 0
, O 0
cannabis B-Chemical 0
/ O 0
alcohol B-Chemical 0
/ O 0
nicotine B-Chemical 0
( O 0
CAN B-Chemical 0
) O 0
, O 0
non O 0
- O 0
ecstasy B-Chemical 0
polydrug O 0
( O 0
PD O 0
) O 0
) O 0
, O 0
and O 0
two O 0
ecstasy B-Chemical 0
polydrug O 0
groups O 0
( O 0
present O 0
( O 0
MDMA B-Chemical 0
) O 0
and O 0
past O 0
users O 0
( O 0
EX O 0
- O 0
MDMA B-Chemical 0
) O 0
. O 0

Participants O 0
completed O 0
a O 0
drug O 0
history O 0
questionnaire O 0
, O 0
Beck O 0
Depression B-Disease 0
Inventory O 0
, O 0
Barratt O 0
Impulsiveness B-Disease 0
Scale O 0
, O 0
Pittsburgh O 0
Sleep O 0
Quality O 0
Index O 0
, O 0
and O 0
Wechsler O 0
Memory O 0
Scale O 0
- O 0
Revised O 0
which O 0
, O 0
in O 0
total O 0
, O 0
provided O 0
13 O 0
psychometric O 0
measures O 0
. O 0

RESULTS O 0
: O 0
While O 0
the O 0
CAN B-Chemical 0
and O 0
PD O 0
groups O 0
tended O 0
to O 0
record O 0
greater O 0
deficits O 0
than O 0
the O 0
non O 0
- O 0
drug O 0
controls O 0
, O 0
the O 0
MDMA B-Chemical 0
and O 0
EX O 0
- O 0
MDMA B-Chemical 0
groups O 0
recorded O 0
greater O 0
deficits O 0
than O 0
all O 0
the O 0
control O 0
groups O 0
on O 0
ten O 0
of O 0
the O 0
13 O 0
psychometric O 0
measures O 0
. O 0

Strikingly O 0
, O 0
despite O 0
prolonged O 0
abstinence O 0
( O 0
mean O 0
, O 0
4 O 0
. O 0
98 O 0
; O 0
range O 0
, O 0
4 O 0
- O 0
9 O 0
years O 0
) O 0
, O 0
past O 0
ecstasy B-Chemical 0
users O 0
showed O 0
few O 0
signs O 0
of O 0
recovery O 0
. O 0

Compared O 0
with O 0
present O 0
ecstasy B-Chemical 0
users O 0
, O 0
the O 0
past O 0
users O 0
showed O 0
no O 0
change O 0
for O 0
ten O 0
measures O 0
, O 0
increased O 0
impairment O 0
for O 0
two O 0
measures O 0
, O 0
and O 0
improvement O 0
on O 0
just O 0
one O 0
measure O 0
. O 0

CONCLUSIONS O 0
: O 0
Given O 0
this O 0
record O 0
of O 0
impaired B-Disease 0
memory I-Disease 0
and O 0
clinically O 0
significant O 0
levels O 0
of O 0
depression B-Disease 0
, O 0
impulsiveness B-Disease 0
, O 0
and O 0
sleep B-Disease 0
disturbance I-Disease 0
, O 0
the O 0
prognosis O 0
for O 0
the O 0
current O 0
generation O 0
of O 0
ecstasy B-Chemical 0
users O 0
is O 0
a O 0
major O 0
cause O 0
for O 0
concern O 0
. O 0

Association O 0
of O 0
common O 0
genetic O 0
variants O 0
of O 0
HOMER1 O 0
gene O 0
with O 0
levodopa B-Chemical 0
adverse O 0
effects O 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
patients O 0
. O 0

Levodopa B-Chemical 0
is O 0
the O 0
most O 0
effective O 0
symptomatic O 0
therapy O 0
for O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
, O 0
but O 0
its O 0
chronic O 0
use O 0
could O 0
lead O 0
to O 0
chronic O 0
adverse O 0
outcomes O 0
, O 0
such O 0
as O 0
motor O 0
fluctuations O 0
, O 0
dyskinesia B-Disease 0
and O 0
visual B-Disease 0
hallucinations I-Disease 0
. O 0

HOMER1 O 0
is O 0
a O 0
protein O 0
with O 0
pivotal O 0
function O 0
in O 0
glutamate B-Chemical 0
transmission O 0
, O 0
which O 0
has O 0
been O 0
related O 0
to O 0
the O 0
pathogenesis O 0
of O 0
these O 0
complications O 0
. O 0

This O 0
study O 0
investigates O 0
whether O 0
polymorphisms O 0
in O 0
the O 0
HOMER1 O 0
gene O 0
promoter O 0
region O 0
are O 0
associated O 0
with O 0
the O 0
occurrence O 0
of O 0
the O 0
chronic O 0
complications O 0
of O 0
levodopa B-Chemical 0
therapy O 0
. O 0

A O 0
total O 0
of O 0
205 O 0
patients O 0
with O 0
idiopathic B-Disease 0
Parkinson I-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
were O 0
investigated O 0
. O 0

Patients O 0
were O 0
genotyped O 0
for O 0
rs4704559 O 0
, O 0
rs10942891 O 0
and O 0
rs4704560 O 0
by O 0
allelic O 0
discrimination O 0
with O 0
Taqman O 0
assays O 0
. O 0

The O 0
rs4704559 O 0
G O 0
allele O 0
was O 0
associated O 0
with O 0
a O 0
lower O 0
prevalence O 0
of O 0
dyskinesia B-Disease 0
( O 0
prevalence O 0
ratio O 0
( O 0
PR O 0
) O 0
= O 0
0 O 0
. O 0
615 O 0
, O 0
95 O 0
% O 0
confidence O 0
interval O 0
( O 0
CI O 0
) O 0
0 O 0
. O 0
426 O 0
- O 0
0 O 0
. O 0
887 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
009 O 0
) O 0
and O 0
visual B-Disease 0
hallucinations I-Disease 0
( O 0
PR O 0
= O 0
0 O 0
. O 0
515 O 0
, O 0
95 O 0
% O 0
CI O 0
0 O 0
. O 0
295 O 0
- O 0
0 O 0
. O 0
899 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
020 O 0
) O 0
. O 0

Our O 0
data O 0
suggest O 0
that O 0
HOMER1 O 0
rs4704559 O 0
G O 0
allele O 0
has O 0
a O 0
protective O 0
role O 0
for O 0
the O 0
development O 0
of O 0
levodopa B-Chemical 0
adverse O 0
effects O 0
. O 0

Crocin B-Chemical 0
improves O 0
lipid O 0
dysregulation O 0
in O 0
subacute O 0
diazinon B-Chemical 0
exposure O 0
through O 0
ERK1 O 0
/ O 0
2 O 0
pathway O 0
in O 0
rat O 0
liver O 0
. O 0

INTRODUCTION O 0
: O 0
Diazinon B-Chemical 0
Yis O 0
one O 0
of O 0
the O 0
most O 0
broadly O 0
used O 0
organophosphorus B-Chemical 0
insecticides O 0
in O 0
agriculture O 0
. O 0

It O 0
has O 0
been O 0
shown O 0
that O 0
exposure O 0
to O 0
diazinon B-Chemical 0
may O 0
interfere O 0
with O 0
lipid O 0
metabolism O 0
. O 0

Moreover O 0
, O 0
the O 0
hypolipidemic O 0
effect O 0
of O 0
crocin B-Chemical 0
has O 0
been O 0
established O 0
. O 0

Earlier O 0
studies O 0
revealed O 0
the O 0
major O 0
role O 0
of O 0
Extracellular O 0
signal O 0
- O 0
regulated O 0
kinase O 0
( O 0
ERK O 0
) O 0
pathways O 0
in O 0
low O 0
- O 0
density O 0
lipoprotein O 0
receptor O 0
( O 0
LDLr O 0
) O 0
expression O 0
. O 0

The O 0
aim O 0
of O 0
this O 0
study O 0
was O 0
to O 0
evaluate O 0
changes O 0
in O 0
the O 0
regulation O 0
of O 0
lipid O 0
metabolism O 0
, O 0
ERK O 0
and O 0
LDLr O 0
expression O 0
in O 0
the O 0
liver O 0
of O 0
rats O 0
exposed O 0
to O 0
subacute O 0
diazinon B-Chemical 0
. O 0

Furthermore O 0
ameliorating O 0
effect O 0
of O 0
crocin B-Chemical 0
on O 0
diazinon B-Chemical 0
induced O 0
disturbed O 0
cholesterol B-Chemical 0
homeostasis O 0
was O 0
studied O 0
. O 0

METHODS O 0
: O 0
24 O 0
Rats O 0
were O 0
divided O 0
into O 0
4 O 0
groups O 0
and O 0
received O 0
following O 0
treatments O 0
for O 0
4 O 0
weeks O 0
; O 0
Corn O 0
oil O 0
( O 0
control O 0
) O 0
, O 0
diazinon B-Chemical 0
( O 0
15mg O 0
/ O 0
kg O 0
per O 0
day O 0
, O 0
orally O 0
) O 0
and O 0
crocin B-Chemical 0
( O 0
12 O 0
. O 0
5 O 0
and O 0
25mg O 0
/ O 0
kg O 0
per O 0
day O 0
, O 0
intraperitoneally O 0
) O 0
in O 0
combination O 0
with O 0
diazinon B-Chemical 0
( O 0
15 O 0
mg O 0
/ O 0
kg O 0
) O 0
. O 0

The O 0
levels O 0
of O 0
cholesterol B-Chemical 0
, O 0
triglyceride B-Chemical 0
and O 0
LDL O 0
in O 0
blood O 0
of O 0
rats O 0
were O 0
analyzed O 0
. O 0

Moreover O 0
mRNA O 0
levels O 0
of O 0
LDLr O 0
and O 0
ERK1 O 0
/ O 0
2 O 0
as O 0
well O 0
as O 0
protein O 0
levels O 0
of O 0
total O 0
and O 0
activated O 0
forms O 0
of O 0
ERK1 O 0
/ O 0
2 O 0
in O 0
rat O 0
liver O 0
were O 0
evaluated O 0
by O 0
Western O 0
blotting O 0
and O 0
quantitative O 0
real O 0
time O 0
polymerase O 0
chain O 0
reaction O 0
analysis O 0
. O 0

RESULTS O 0
: O 0
Our O 0
data O 0
showed O 0
that O 0
subacute O 0
exposure O 0
to O 0
diazinon B-Chemical 0
significantly O 0
increased O 0
concentrations O 0
of O 0
cholesterol B-Chemical 0
, O 0
triglyceride B-Chemical 0
and O 0
LDL O 0
. O 0

Moreover O 0
diazinon B-Chemical 0
decreased O 0
ERK1 O 0
/ O 0
2 O 0
protein O 0
phosphorylation O 0
and O 0
LDLr O 0
transcript O 0
. O 0

Crocin B-Chemical 0
reduced O 0
inhibition O 0
of O 0
ERK O 0
activation O 0
and O 0
diazinon B-Chemical 0
- O 0
induced O 0
hyperlipemia B-Disease 0
and O 0
increased O 0
levels O 0
of O 0
LDLr O 0
transcript O 0
. O 0

CONCLUSIONS O 0
: O 0
Crocin B-Chemical 0
may O 0
be O 0
considered O 0
as O 0
a O 0
novel O 0
protective O 0
agent O 0
in O 0
diazinon B-Chemical 0
- O 0
induced O 0
hyperlipemia B-Disease 0
through O 0
modulating O 0
of O 0
ERK O 0
pathway O 0
and O 0
increase O 0
of O 0
LDLr O 0
expression O 0
. O 0

GEM B-Chemical 0
- O 0
P O 0
chemotherapy O 0
is O 0
active O 0
in O 0
the O 0
treatment O 0
of O 0
relapsed O 0
Hodgkin B-Disease 0
lymphoma I-Disease 0
. O 0

Hodgkin B-Disease 0
lymphoma I-Disease 0
( O 0
HL B-Disease 0
) O 0
is O 0
a O 0
relatively O 0
chemosensitive O 0
malignancy B-Disease 0
. O 0

However O 0
, O 0
for O 0
those O 0
who O 0
relapse O 0
, O 0
high O 0
- O 0
dose O 0
chemotherapy O 0
with O 0
autologous O 0
stem O 0
cell O 0
transplant O 0
is O 0
the O 0
treatment O 0
of O 0
choice O 0
which O 0
relies O 0
on O 0
adequate O 0
disease O 0
control O 0
with O 0
salvage O 0
chemotherapy O 0
. O 0

Regimens O 0
commonly O 0
used O 0
often O 0
require O 0
inpatient O 0
administration O 0
and O 0
can O 0
be O 0
difficult O 0
to O 0
deliver O 0
due O 0
to O 0
toxicity B-Disease 0
. O 0

Gemcitabine B-Chemical 0
and O 0
cisplatin B-Chemical 0
have O 0
activity O 0
in O 0
HL B-Disease 0
, O 0
non O 0
- O 0
overlapping O 0
toxicity B-Disease 0
with O 0
first O 0
- O 0
line O 0
chemotherapeutics O 0
, O 0
and O 0
may O 0
be O 0
delivered O 0
in O 0
an O 0
outpatient O 0
setting O 0
. O 0

In O 0
this O 0
retrospective O 0
single O 0
- O 0
centre O 0
analysis O 0
, O 0
patients O 0
with O 0
relapsed O 0
or O 0
refractory O 0
HL B-Disease 0
treated O 0
with O 0
gemcitabine B-Chemical 0
1 O 0
, O 0
000 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
day O 0
( O 0
D O 0
) O 0
1 O 0
, O 0
D8 O 0
and O 0
D15 O 0
; O 0
methylprednisolone B-Chemical 0
1 O 0
, O 0
000 O 0
mg O 0
D1 O 0
- O 0
5 O 0
; O 0
and O 0
cisplatin B-Chemical 0
100 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
D15 O 0
, O 0
every O 0
28 O 0
days O 0
( O 0
GEM B-Chemical 0
- O 0
P O 0
) O 0
were O 0
included O 0
. O 0

Demographic O 0
, O 0
survival O 0
, O 0
response O 0
and O 0
toxicity B-Disease 0
data O 0
were O 0
recorded O 0
. O 0

Forty O 0
- O 0
one O 0
eligible O 0
patients O 0
were O 0
identified O 0
: O 0
median O 0
age O 0
27 O 0
. O 0

One O 0
hundred O 0
and O 0
twenty O 0
- O 0
two O 0
cycles O 0
of O 0
GEM B-Chemical 0
- O 0
P O 0
were O 0
administered O 0
in O 0
total O 0
( O 0
median O 0
3 O 0
cycles O 0
; O 0
range O 0
1 O 0
- O 0
6 O 0
) O 0
. O 0

Twenty O 0
of O 0
41 O 0
( O 0
48 O 0
% O 0
) O 0
patients O 0
received O 0
GEM B-Chemical 0
- O 0
P O 0
as O 0
second O 0
- O 0
line O 0
treatment O 0
and O 0
11 O 0
/ O 0
41 O 0
( O 0
27 O 0
% O 0
) O 0
as O 0
third O 0
- O 0
line O 0
therapy O 0
. O 0

Overall O 0
response O 0
rate O 0
( O 0
ORR O 0
) O 0
to O 0
GEM B-Chemical 0
- O 0
P O 0
in O 0
the O 0
entire O 0
cohort O 0
was O 0
80 O 0
% O 0
( O 0
complete O 0
response O 0
( O 0
CR O 0
) O 0
37 O 0
% O 0
, O 0
partial O 0
response O 0
44 O 0
% O 0
) O 0
with O 0
14 O 0
/ O 0
15 O 0
CR O 0
confirmed O 0
as O 0
a O 0
metabolic O 0
CR O 0
on O 0
PET O 0
and O 0
ORR O 0
of O 0
85 O 0
% O 0
in O 0
the O 0
20 O 0
second O 0
- O 0
line O 0
patients O 0
. O 0

The O 0
most O 0
common O 0
grade O 0
3 O 0
/ O 0
4 O 0
toxicities B-Disease 0
were O 0
haematological O 0
: O 0
neutropenia B-Disease 0
54 O 0
% O 0
and O 0
thrombocytopenia B-Disease 0
51 O 0
% O 0
. O 0

Median O 0
follow O 0
- O 0
up O 0
from O 0
the O 0
start O 0
of O 0
GEM B-Chemical 0
- O 0
P O 0
was O 0
4 O 0
. O 0
5 O 0
years O 0
. O 0

Following O 0
GEM B-Chemical 0
- O 0
P O 0
, O 0
5 O 0
- O 0
year O 0
progression O 0
- O 0
free O 0
survival O 0
was O 0
46 O 0
% O 0
( O 0
95 O 0
% O 0
confidence O 0
interval O 0
( O 0
CI O 0
) O 0
, O 0
30 O 0
- O 0
62 O 0
% O 0
) O 0
and O 0
5 O 0
- O 0
year O 0
overall O 0
survival O 0
was O 0
59 O 0
% O 0
( O 0
95 O 0
% O 0
CI O 0
, O 0
43 O 0
- O 0
74 O 0
% O 0
) O 0
. O 0

Fourteen O 0
of O 0
41 O 0
patients O 0
proceeded O 0
directly O 0
to O 0
autologous O 0
transplant O 0
. O 0

GEM B-Chemical 0
- O 0
P O 0
is O 0
a O 0
salvage O 0
chemotherapy O 0
with O 0
relatively O 0
high O 0
response O 0
rates O 0
, O 0
leading O 0
to O 0
successful O 0
transplantation O 0
in O 0
appropriate O 0
patients O 0
, O 0
in O 0
the O 0
treatment O 0
of O 0
relapsed O 0
or O 0
refractory O 0
HL B-Disease 0
. O 0

Basal O 0
functioning O 0
of O 0
the O 0
hypothalamic O 0
- O 0
pituitary O 0
- O 0
adrenal O 0
( O 0
HPA O 0
) O 0
axis O 0
and O 0
psychological O 0
distress O 0
in O 0
recreational O 0
ecstasy B-Chemical 0
polydrug O 0
users O 0
. O 0

RATIONALE O 0
: O 0
Ecstasy B-Chemical 0
( O 0
MDMA B-Chemical 0
) O 0
is O 0
a O 0
psychostimulant O 0
drug O 0
which O 0
is O 0
increasingly O 0
associated O 0
with O 0
psychobiological B-Disease 0
dysfunction I-Disease 0
. O 0

While O 0
some O 0
recent O 0
studies O 0
suggest O 0
acute O 0
changes O 0
in O 0
neuroendocrine O 0
function O 0
, O 0
less O 0
is O 0
known O 0
about O 0
long O 0
- O 0
term O 0
changes O 0
in O 0
HPA O 0
functionality O 0
in O 0
recreational O 0
users O 0
. O 0

OBJECTIVES O 0
: O 0
The O 0
current O 0
study O 0
is O 0
the O 0
first O 0
to O 0
explore O 0
the O 0
effects O 0
of O 0
ecstasy B-Chemical 0
- O 0
polydrug O 0
use O 0
on O 0
psychological O 0
distress O 0
and O 0
basal O 0
functioning O 0
of O 0
the O 0
HPA O 0
axis O 0
through O 0
assessing O 0
the O 0
secretion O 0
of O 0
cortisol B-Chemical 0
across O 0
the O 0
diurnal O 0
period O 0
. O 0

METHOD O 0
: O 0
Seventy O 0
- O 0
six O 0
participants O 0
( O 0
21 O 0
nonusers O 0
, O 0
29 O 0
light O 0
ecstasy B-Chemical 0
- O 0
polydrug O 0
users O 0
, O 0
26 O 0
heavy O 0
ecstasy B-Chemical 0
- O 0
polydrug O 0
users O 0
) O 0
completed O 0
a O 0
substance O 0
use O 0
inventory O 0
and O 0
measures O 0
of O 0
psychological O 0
distress O 0
at O 0
baseline O 0
, O 0
then O 0
two O 0
consecutive O 0
days O 0
of O 0
cortisol B-Chemical 0
sampling O 0
( O 0
on O 0
awakening O 0
, O 0
30 O 0
min O 0
post O 0
awakening O 0
, O 0
between O 0
1400 O 0
and O 0
1600 O 0
hours O 0
and O 0
pre O 0
bedtime O 0
) O 0
. O 0

On O 0
day O 0
2 O 0
, O 0
participants O 0
also O 0
attended O 0
the O 0
laboratory O 0
to O 0
complete O 0
a O 0
20 O 0
- O 0
min O 0
multitasking O 0
stressor O 0
. O 0

RESULTS O 0
: O 0
Both O 0
user O 0
groups O 0
exhibited O 0
significantly O 0
greater O 0
levels O 0
of O 0
anxiety B-Disease 0
and O 0
depression B-Disease 0
than O 0
nonusers O 0
. O 0

On O 0
day O 0
1 O 0
, O 0
all O 0
participants O 0
exhibited O 0
a O 0
typical O 0
cortisol B-Chemical 0
profile O 0
, O 0
though O 0
light O 0
users O 0
had O 0
significantly O 0
elevated O 0
levels O 0
pre O 0
- O 0
bed O 0
. O 0

On O 0
day O 0
2 O 0
, O 0
heavy O 0
users O 0
demonstrated O 0
elevated O 0
levels O 0
upon O 0
awakening O 0
and O 0
all O 0
ecstasy B-Chemical 0
- O 0
polydrug O 0
users O 0
demonstrated O 0
elevated O 0
pre O 0
- O 0
bed O 0
levels O 0
compared O 0
to O 0
non O 0
- O 0
users O 0
. O 0

Significant O 0
between O 0
group O 0
differences O 0
were O 0
also O 0
observed O 0
in O 0
afternoon O 0
cortisol B-Chemical 0
levels O 0
and O 0
in O 0
overall O 0
cortisol B-Chemical 0
secretion O 0
across O 0
the O 0
day O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
increases O 0
in O 0
anxiety B-Disease 0
and O 0
depression B-Disease 0
are O 0
in O 0
line O 0
with O 0
previous O 0
observations O 0
in O 0
recreational O 0
ecstasy B-Chemical 0
- O 0
polydrug O 0
users O 0
. O 0

Dysregulated O 0
diurnal O 0
cortisol B-Chemical 0
may O 0
be O 0
indicative O 0
of O 0
inappropriate O 0
anticipation O 0
of O 0
forthcoming O 0
demands O 0
and O 0
hypersecretion O 0
may O 0
lead O 0
to O 0
the O 0
increased O 0
psychological O 0
and O 0
physical O 0
morbidity O 0
associated O 0
with O 0
heavy O 0
recreational O 0
use O 0
of O 0
ecstasy B-Chemical 0
. O 0

Ifosfamide B-Chemical 0
related O 0
encephalopathy B-Disease 0
: O 0
the O 0
need O 0
for O 0
a O 0
timely O 0
EEG O 0
evaluation O 0
. O 0

BACKGROUND O 0
: O 0
Ifosfamide B-Chemical 0
is O 0
an O 0
alkylating O 0
agent O 0
useful O 0
in O 0
the O 0
treatment O 0
of O 0
a O 0
wide O 0
range O 0
of O 0
cancers B-Disease 0
including O 0
sarcomas B-Disease 0
, O 0
lymphoma B-Disease 0
, O 0
gynecologic B-Disease 0
and I-Disease 0
testicular I-Disease 0
cancers I-Disease 0
. O 0

Encephalopathy B-Disease 0
has O 0
been O 0
reported O 0
in O 0
10 O 0
- O 0
40 O 0
% O 0
of O 0
patients O 0
receiving O 0
high O 0
- O 0
dose O 0
IV O 0
ifosfamide B-Chemical 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
highlight O 0
the O 0
role O 0
of O 0
electroencephalogram O 0
( O 0
EEG O 0
) O 0
in O 0
the O 0
early O 0
detection O 0
and O 0
management O 0
of O 0
ifosfamide B-Chemical 0
related O 0
encephalopathy B-Disease 0
. O 0

METHODS O 0
: O 0
Retrospective O 0
chart O 0
review O 0
including O 0
clinical O 0
data O 0
and O 0
EEG O 0
recordings O 0
was O 0
done O 0
on O 0
five O 0
patients O 0
, O 0
admitted O 0
to O 0
MD O 0
Anderson O 0
Cancer B-Disease 0
Center O 0
between O 0
years O 0
2009 O 0
and O 0
2012 O 0
, O 0
who O 0
developed O 0
ifosfamide B-Chemical 0
related O 0
acute O 0
encephalopathy B-Disease 0
. O 0

RESULTS O 0
: O 0
All O 0
five O 0
patients O 0
experienced O 0
symptoms O 0
of O 0
encephalopathy B-Disease 0
soon O 0
after O 0
( O 0
within O 0
12 O 0
h O 0
- O 0
2 O 0
days O 0
) O 0
receiving O 0
ifosfamide B-Chemical 0
. O 0

Two O 0
patients O 0
developed O 0
generalized O 0
convulsions B-Disease 0
while O 0
one O 0
patient O 0
developed O 0
continuous O 0
non B-Disease 0
- I-Disease 0
convulsive I-Disease 0
status I-Disease 0
epilepticus I-Disease 0
( O 0
NCSE B-Disease 0
) O 0
that O 0
required O 0
ICU O 0
admission O 0
and O 0
intubation O 0
. O 0

Initial O 0
EEG O 0
showed O 0
epileptiform O 0
discharges O 0
in O 0
three O 0
patients O 0
; O 0
run O 0
of O 0
triphasic O 0
waves O 0
in O 0
one O 0
patient O 0
and O 0
moderate O 0
degree O 0
diffuse O 0
generalized O 0
slowing O 0
. O 0

Mixed O 0
pattern O 0
with O 0
the O 0
presence O 0
of O 0
both O 0
sharps O 0
and O 0
triphasic O 0
waves O 0
were O 0
also O 0
noted O 0
. O 0

Repeat O 0
EEGs O 0
within O 0
24 O 0
_ O 0
h O 0
of O 0
symptom O 0
onset O 0
showed O 0
marked O 0
improvement O 0
that O 0
was O 0
correlated O 0
with O 0
clinical O 0
improvement O 0
. O 0

CONCLUSIONS O 0
: O 0
Severity O 0
of O 0
ifosfamide B-Chemical 0
related O 0
encephalopathy B-Disease 0
correlates O 0
with O 0
EEG O 0
changes O 0
. O 0

We O 0
suggest O 0
a O 0
timely O 0
EEG O 0
evaluation O 0
for O 0
patients O 0
receiving O 0
ifosfamide B-Chemical 0
who O 0
develop O 0
features O 0
of O 0
encephalopathy B-Disease 0
. O 0

Incidence O 0
of O 0
contrast B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
in O 0
hospitalised O 0
patients O 0
with O 0
cancer B-Disease 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
determine O 0
the O 0
frequency O 0
of O 0
and O 0
possible O 0
factors O 0
related O 0
to O 0
contrast B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
( O 0
CIN O 0
) O 0
in O 0
hospitalised O 0
patients O 0
with O 0
cancer B-Disease 0
. O 0

METHODS O 0
: O 0
Ninety O 0
adult O 0
patients O 0
were O 0
enrolled O 0
. O 0

Patients O 0
with O 0
risk O 0
factors O 0
for O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
were O 0
excluded O 0
. O 0

Blood O 0
samples O 0
were O 0
examined O 0
the O 0
day O 0
before O 0
contrast B-Chemical 0
- O 0
enhanced O 0
computed O 0
tomography O 0
( O 0
CT O 0
) O 0
and O 0
serially O 0
for O 0
3 O 0
days O 0
thereafter O 0
. O 0

CIN O 0
was O 0
defined O 0
as O 0
an O 0
increase O 0
in O 0
serum O 0
creatinine B-Chemical 0
( O 0
Cr B-Chemical 0
) O 0
of O 0
0 O 0
. O 0
5 O 0
mg O 0
/ O 0
dl O 0
or O 0
more O 0
, O 0
or O 0
elevation O 0
of O 0
Cr B-Chemical 0
to O 0
25 O 0
% O 0
over O 0
baseline O 0
. O 0

Relationships O 0
between O 0
CIN O 0
and O 0
possible O 0
risk O 0
factors O 0
were O 0
investigated O 0
. O 0

RESULTS O 0
: O 0
CIN O 0
was O 0
detected O 0
in O 0
18 O 0
/ O 0
90 O 0
( O 0
20 O 0
% O 0
) O 0
patients O 0
. O 0

CIN O 0
developed O 0
in O 0
25 O 0
. O 0
5 O 0
% O 0
patients O 0
who O 0
underwent O 0
chemotherapy O 0
and O 0
in O 0
11 O 0
% O 0
patients O 0
who O 0
did O 0
not O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
1 O 0
) O 0
. O 0

CIN O 0
more O 0
frequently O 0
developed O 0
in O 0
patients O 0
who O 0
had O 0
undergone O 0
CT O 0
within O 0
45 O 0
days O 0
after O 0
the O 0
last O 0
chemotherapy O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
005 O 0
) O 0
; O 0
it O 0
was O 0
also O 0
an O 0
independent O 0
risk O 0
factor O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
017 O 0
) O 0
. O 0

CIN O 0
was O 0
significantly O 0
more O 0
after O 0
treatment O 0
with O 0
bevacizumab B-Chemical 0
/ O 0
irinotecan B-Chemical 0
( O 0
P O 0
= O 0
0 O 0
. O 0
021 O 0
) O 0
and O 0
in O 0
patients O 0
with O 0
hypertension B-Disease 0
( O 0
P O 0
= O 0
0 O 0
. O 0
044 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
incidence O 0
of O 0
CIN O 0
after O 0
CT O 0
in O 0
hospitalised O 0
oncological O 0
patients O 0
was O 0
20 O 0
% O 0
. O 0

CIN O 0
developed O 0
4 O 0
. O 0
5 O 0
- O 0
times O 0
more O 0
frequently O 0
in O 0
patients O 0
with O 0
cancer B-Disease 0
who O 0
had O 0
undergone O 0
recent O 0
chemotherapy O 0
. O 0

Hypertension B-Disease 0
and O 0
the O 0
combination O 0
of O 0
bevacizumab B-Chemical 0
/ O 0
irinotecan B-Chemical 0
may O 0
be O 0
additional O 0
risk O 0
factors O 0
for O 0
CIN O 0
development O 0
. O 0

KEY O 0
POINTS O 0
: O 0
. O 0

Contrast B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
( O 0
CIN O 0
) O 0
is O 0
a O 0
concern O 0
for O 0
oncological O 0
patients O 0
undergoing O 0
CT O 0
. O 0

. O 0
CIN O 0
occurs O 0
more O 0
often O 0
when O 0
CT O 0
is O 0
performed O 0
< O 0
45 O 0
days O 0
after O 0
chemotherapy O 0
. O 0

. O 0
Hypertension B-Disease 0
and O 0
treatment O 0
with O 0
bevacizumab B-Chemical 0
appear O 0
to O 0
be O 0
additional O 0
risk O 0
factors O 0
. O 0

Syndrome B-Disease 0
of I-Disease 0
inappropriate I-Disease 0
antidiuretic I-Disease 0
hormone I-Disease 0
secretion O 0
associated O 0
with O 0
desvenlafaxine B-Chemical 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
report O 0
a O 0
case O 0
of O 0
syndrome B-Disease 0
of I-Disease 0
inappropriate I-Disease 0
anti I-Disease 0
- I-Disease 0
diuretic I-Disease 0
hormone I-Disease 0
( O 0
SIADH B-Disease 0
) O 0
secretion O 0
associated O 0
with O 0
desvenlafaxine B-Chemical 0
. O 0

CASE O 0
SUMMARY O 0
: O 0
A O 0
57 O 0
- O 0
year O 0
old O 0
female O 0
with O 0
hyponatraemia B-Disease 0
. O 0

Her O 0
medications O 0
included O 0
desvenlafaxine B-Chemical 0
, O 0
and O 0
symptoms O 0
included O 0
nausea B-Disease 0
, O 0
anxiety B-Disease 0
and O 0
confusion B-Disease 0
. O 0

The O 0
serum O 0
sodium B-Chemical 0
at O 0
this O 0
time O 0
was O 0
120 O 0
mmol O 0
/ O 0
L O 0
, O 0
serum O 0
osmolality O 0
was O 0
263 O 0
mosmol O 0
/ O 0
kg O 0
, O 0
urine O 0
osmolality O 0
410 O 0
mosmol O 0
/ O 0
kg O 0
and O 0
urine O 0
sodium B-Chemical 0
63 O 0
mmol O 0
/ O 0
L O 0
, O 0
consistent O 0
with O 0
a O 0
diagnosis O 0
of O 0
SIADH B-Disease 0
. O 0

Desvenlafaxine B-Chemical 0
was O 0
ceased O 0
and O 0
fluid O 0
restriction O 0
implemented O 0
. O 0

After O 0
4 O 0
days O 0
the O 0
sodium B-Chemical 0
increased O 0
to O 0
128 O 0
mmol O 0
/ O 0
L O 0
and O 0
fluid O 0
restriction O 0
was O 0
relaxed O 0
. O 0

During O 0
her O 0
further O 0
3 O 0
weeks O 0
inpatient O 0
admission O 0
the O 0
serum O 0
sodium B-Chemical 0
ranged O 0
from O 0
134 O 0
to O 0
137 O 0
mmol O 0
/ O 0
L O 0
during O 0
treatment O 0
with O 0
mirtazapine B-Chemical 0
. O 0

DISCUSSION O 0
: O 0
SIADH B-Disease 0
has O 0
been O 0
widely O 0
reported O 0
with O 0
a O 0
range O 0
of O 0
antidepressants O 0
. O 0

This O 0
case O 0
report O 0
suggests O 0
that O 0
desvenlafaxine B-Chemical 0
might O 0
cause O 0
clinically O 0
significant O 0
hyponatremia B-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
Clinicians O 0
should O 0
be O 0
aware O 0
of O 0
the O 0
potential O 0
for O 0
antidepressants O 0
to O 0
cause O 0
hyponatremia B-Disease 0
, O 0
and O 0
take O 0
appropriate O 0
corrective O 0
action O 0
where O 0
necessary O 0
. O 0

Oxidative O 0
stress O 0
on O 0
cardiotoxicity B-Disease 0
after O 0
treatment O 0
with O 0
single O 0
and O 0
multiple O 0
doses O 0
of O 0
doxorubicin B-Chemical 0
. O 0

The O 0
mechanism O 0
of O 0
doxorubicin B-Chemical 0
( O 0
DOX B-Chemical 0
) O 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
remains O 0
controversial O 0
. O 0

Wistar O 0
rats O 0
( O 0
n O 0
= O 0
66 O 0
) O 0
received O 0
DOX B-Chemical 0
injections O 0
intraperitoneally O 0
and O 0
were O 0
randomly O 0
assigned O 0
to O 0
2 O 0
experimental O 0
protocols O 0
: O 0
( O 0
1 O 0
) O 0
rats O 0
were O 0
killed O 0
before O 0
( O 0
- O 0
24 O 0
h O 0
, O 0
n O 0
= O 0
8 O 0
) O 0
and O 0
24 O 0
h O 0
after O 0
( O 0
+ O 0
24 O 0
h O 0
, O 0
n O 0
= O 0
8 O 0
) O 0
a O 0
single O 0
dose O 0
of O 0
DOX B-Chemical 0
( O 0
4 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
) O 0
to O 0
determine O 0
the O 0
DOX B-Chemical 0
acute O 0
effect O 0
and O 0
( O 0
2 O 0
) O 0
rats O 0
( O 0
n O 0
= O 0
58 O 0
) O 0
received O 0
4 O 0
injections O 0
of O 0
DOX B-Chemical 0
( O 0
4 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
/ O 0
week O 0
) O 0
and O 0
were O 0
killed O 0
before O 0
the O 0
first O 0
injection O 0
( O 0
M0 O 0
) O 0
and O 0
1 O 0
week O 0
after O 0
each O 0
injection O 0
( O 0
M1 O 0
, O 0
M2 O 0
, O 0
M3 O 0
, O 0
and O 0
M4 O 0
) O 0
to O 0
determine O 0
the O 0
chronological O 0
effects O 0
. O 0

Animals O 0
used O 0
at O 0
M0 O 0
( O 0
n O 0
= O 0
8 O 0
) O 0
were O 0
also O 0
used O 0
at O 0
moment O 0
- O 0
24 O 0
h O 0
of O 0
acute O 0
study O 0
. O 0

Cardiac O 0
total O 0
antioxidant O 0
performance O 0
( O 0
TAP O 0
) O 0
, O 0
DNA O 0
damage O 0
, O 0
and O 0
morphology O 0
analyses O 0
were O 0
carried O 0
out O 0
at O 0
each O 0
time O 0
point O 0
. O 0

Single O 0
dose O 0
of O 0
DOX B-Chemical 0
was O 0
associated O 0
with O 0
increased O 0
cardiac B-Disease 0
disarrangement I-Disease 0
, O 0
necrosis B-Disease 0
, O 0
and O 0
DNA O 0
damage O 0
( O 0
strand O 0
breaks O 0
( O 0
SBs O 0
) O 0
and O 0
oxidized O 0
pyrimidines O 0
) O 0
and O 0
decreased O 0
TAP O 0
. O 0

The O 0
chronological O 0
study O 0
showed O 0
an O 0
effect O 0
of O 0
a O 0
cumulative O 0
dose O 0
on O 0
body O 0
weight O 0
( O 0
R O 0
= O 0
- O 0
0 O 0
. O 0
99 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
011 O 0
) O 0
, O 0
necrosis B-Disease 0
( O 0
R O 0
= O 0
1 O 0
. O 0
00 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
004 O 0
) O 0
, O 0
TAP O 0
( O 0
R O 0
= O 0
0 O 0
. O 0
95 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
049 O 0
) O 0
, O 0
and O 0
DNA O 0
SBs O 0
( O 0
R O 0
= O 0
- O 0
0 O 0
. O 0
95 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
049 O 0
) O 0
. O 0

DNA O 0
SBs O 0
damage O 0
was O 0
negatively O 0
associated O 0
with O 0
TAP O 0
( O 0
R O 0
= O 0
- O 0
0 O 0
. O 0
98 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
018 O 0
) O 0
, O 0
and O 0
necrosis B-Disease 0
( O 0
R O 0
= O 0
- O 0
0 O 0
. O 0
97 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
027 O 0
) O 0
. O 0

Our O 0
results O 0
suggest O 0
that O 0
oxidative O 0
damage O 0
is O 0
associated O 0
with O 0
acute O 0
cardiotoxicity B-Disease 0
induced O 0
by O 0
a O 0
single O 0
dose O 0
of O 0
DOX B-Chemical 0
only O 0
. O 0

Increased O 0
resistance O 0
to O 0
the O 0
oxidative O 0
stress O 0
is O 0
plausible O 0
for O 0
the O 0
multiple O 0
dose O 0
of O 0
DOX B-Chemical 0
. O 0

Thus O 0
, O 0
different O 0
mechanisms O 0
may O 0
be O 0
involved O 0
in O 0
acute O 0
toxicity B-Disease 0
versus O 0
chronic O 0
toxicity B-Disease 0
. O 0

Tacrolimus B-Chemical 0
- O 0
related O 0
seizure B-Disease 0
after O 0
pediatric O 0
liver O 0
transplantation O 0
- O 0
- O 0
a O 0
single O 0
- O 0
center O 0
experience O 0
. O 0

To O 0
identify O 0
the O 0
risk O 0
factors O 0
for O 0
new O 0
- O 0
onset O 0
seizures B-Disease 0
after O 0
pediatric O 0
LT O 0
and O 0
to O 0
assess O 0
their O 0
clinical O 0
implications O 0
and O 0
long O 0
- O 0
term O 0
prognosis O 0
. O 0

The O 0
clinical O 0
and O 0
laboratory O 0
data O 0
of O 0
27 O 0
consecutive O 0
children O 0
who O 0
underwent O 0
LT O 0
from O 0
January O 0
2007 O 0
to O 0
December O 0
2010 O 0
in O 0
our O 0
center O 0
were O 0
analyzed O 0
retrospectively O 0
. O 0

Patients O 0
were O 0
divided O 0
into O 0
seizures B-Disease 0
group O 0
and O 0
a O 0
non O 0
- O 0
seizures B-Disease 0
group O 0
. O 0

Pre O 0
- O 0
operative O 0
, O 0
intra O 0
- O 0
operative O 0
, O 0
and O 0
post O 0
- O 0
operative O 0
data O 0
were O 0
collected O 0
. O 0

Seizures B-Disease 0
occurred O 0
in O 0
four O 0
children O 0
, O 0
an O 0
incidence O 0
of O 0
14 O 0
. O 0
8 O 0
% O 0
. O 0

All O 0
exhibited O 0
generalized O 0
tonic B-Disease 0
- I-Disease 0
clonic I-Disease 0
seizures I-Disease 0
within O 0
the O 0
first O 0
two O 0
wk O 0
after O 0
LT O 0
. O 0

Univariate O 0
analysis O 0
showed O 0
that O 0
the O 0
risk O 0
factors O 0
associated O 0
with O 0
seizures B-Disease 0
after O 0
pediatric O 0
LT O 0
included O 0
gender O 0
, O 0
pediatric O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
liver I-Disease 0
disease I-Disease 0
score O 0
before O 0
surgery O 0
, O 0
Child O 0
- O 0
Pugh O 0
score O 0
before O 0
surgery O 0
, O 0
serum O 0
total O 0
bilirubin B-Chemical 0
after O 0
surgery O 0
, O 0
and O 0
trough O 0
TAC B-Chemical 0
level O 0
. O 0

Multivariate O 0
analysis O 0
showed O 0
that O 0
trough O 0
TAC B-Chemical 0
level O 0
was O 0
the O 0
only O 0
independent O 0
risk O 0
factor O 0
associated O 0
with O 0
the O 0
seizures B-Disease 0
. O 0

All O 0
children O 0
who O 0
experienced O 0
seizures B-Disease 0
survived O 0
with O 0
good O 0
graft O 0
function O 0
and O 0
remained O 0
seizure B-Disease 0
- O 0
free O 0
without O 0
anti O 0
- O 0
epileptic B-Disease 0
drugs O 0
over O 0
a O 0
mean O 0
follow O 0
- O 0
up O 0
period O 0
of O 0
33 O 0
. O 0
7 O 0
+ O 0
14 O 0
. O 0
6 O 0
months O 0
. O 0

High O 0
trough O 0
TAC B-Chemical 0
level O 0
was O 0
the O 0
predominant O 0
factor O 0
that O 0
contributed O 0
to O 0
seizures B-Disease 0
in O 0
the O 0
early O 0
post O 0
- O 0
operative O 0
period O 0
after O 0
pediatric O 0
LT O 0
. O 0

High O 0
PELD O 0
and O 0
Child O 0
- O 0
Pugh O 0
scores O 0
before O 0
LT O 0
and O 0
high O 0
post O 0
- O 0
operative O 0
serum O 0
Tbil O 0
may O 0
be O 0
contributory O 0
risk O 0
factors O 0
for O 0
TAC B-Chemical 0
- O 0
related O 0
seizures B-Disease 0
. O 0

The O 0
flavonoid B-Chemical 0
apigenin B-Chemical 0
delays O 0
forgetting O 0
of O 0
passive O 0
avoidance O 0
conditioning O 0
in O 0
rats O 0
. O 0

The O 0
present O 0
experiments O 0
were O 0
performed O 0
to O 0
study O 0
the O 0
effect O 0
of O 0
the O 0
flavonoid B-Chemical 0
apigenin B-Chemical 0
( O 0
20 O 0
mg O 0
/ O 0
kg O 0
intraperitoneally O 0
( O 0
i O 0
. O 0
p O 0
. O 0
) O 0
, O 0
1 O 0
h O 0
before O 0
acquisition O 0
) O 0
, O 0
on O 0
24 O 0
h O 0
retention O 0
performance O 0
and O 0
forgetting O 0
of O 0
a O 0
step O 0
- O 0
through O 0
passive O 0
avoidance O 0
task O 0
, O 0
in O 0
young O 0
male O 0
Wistar O 0
rats O 0
. O 0

There O 0
were O 0
no O 0
differences O 0
between O 0
saline O 0
- O 0
and O 0
apigenin B-Chemical 0
- O 0
treated O 0
groups O 0
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the O 0
24 O 0
h O 0
retention O 0
trial O 0
. O 0

Furthermore O 0
, O 0
apigenin B-Chemical 0
did O 0
not O 0
prevent O 0
the O 0
amnesia B-Disease 0
induced O 0
by O 0
scopolamine B-Chemical 0
( O 0
1mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
, O 0
30 O 0
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acquisition O 0
) O 0
. O 0

The O 0
saline O 0
- O 0
and O 0
apigenin B-Chemical 0
- O 0
treated O 0
rats O 0
that O 0
did O 0
not O 0
step O 0
through O 0
into O 0
the O 0
dark O 0
compartment O 0
during O 0
the O 0
cut O 0
- O 0
off O 0
time O 0
( O 0
540 O 0
s O 0
) O 0
were O 0
retested O 0
weekly O 0
for O 0
up O 0
to O 0
eight O 0
weeks O 0
. O 0

In O 0
the O 0
saline O 0
treated O 0
group O 0
, O 0
the O 0
first O 0
significant O 0
decline O 0
in O 0
passive O 0
avoidance O 0
response O 0
was O 0
observed O 0
at O 0
four O 0
weeks O 0
, O 0
and O 0
complete O 0
memory B-Disease 0
loss I-Disease 0
was O 0
found O 0
five O 0
weeks O 0
after O 0
the O 0
acquisition O 0
of O 0
the O 0
passive O 0
avoidance O 0
task O 0
. O 0

At O 0
the O 0
end O 0
of O 0
the O 0
experimental O 0
period O 0
, O 0
60 O 0
% O 0
of O 0
the O 0
animals O 0
treated O 0
with O 0
apigenin B-Chemical 0
still O 0
did O 0
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step O 0
through O 0
. O 0

These O 0
data O 0
suggest O 0
that O 0
1 O 0
) O 0
apigenin B-Chemical 0
delays O 0
the O 0
long O 0
- O 0
term O 0
forgetting O 0
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did O 0
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modulate O 0
the O 0
24 O 0
h O 0
retention O 0
of O 0
fear O 0
memory O 0
and O 0
2 O 0
) O 0
the O 0
obtained O 0
beneficial O 0
effect O 0
of O 0
apigenin B-Chemical 0
on O 0
the O 0
passive O 0
avoidance O 0
conditioning O 0
is O 0
mediated O 0
by O 0
mechanisms O 0
that O 0
do O 0
not O 0
implicate O 0
its O 0
action O 0
on O 0
the O 0
muscarinic O 0
cholinergic O 0
system O 0
. O 0

Histamine B-Chemical 0
antagonists O 0
and O 0
d B-Chemical 0
- I-Chemical 0
tubocurarine I-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
in O 0
cardiac O 0
surgical O 0
patients O 0
. O 0

Hemodynamic O 0
effects O 0
and O 0
histamine B-Chemical 0
release O 0
by O 0
bolus O 0
injection O 0
of O 0
0 O 0
. O 0
35 O 0
mg O 0
/ O 0
kg O 0
of O 0
d B-Chemical 0
- I-Chemical 0
tubocurarine I-Chemical 0
were O 0
studied O 0
in O 0
24 O 0
patients O 0
. O 0

H1 O 0
- O 0
and O 0
H2 O 0
- O 0
histamine B-Chemical 0
antagonists O 0
or O 0
placebo O 0
were O 0
given O 0
before O 0
dosing O 0
with O 0
d B-Chemical 0
- I-Chemical 0
tubocurarine I-Chemical 0
in O 0
a O 0
randomized O 0
double O 0
- O 0
blind O 0
fashion O 0
to O 0
four O 0
groups O 0
: O 0
group O 0
1 O 0
- O 0
- O 0
placebo O 0
; O 0
group O 0
2 O 0
- O 0
- O 0
cimetidine B-Chemical 0
, O 0
4 O 0
mg O 0
/ O 0
kg O 0
, O 0
plus O 0
placebo O 0
; O 0
group O 0
3 O 0
- O 0
- O 0
chlorpheniramine B-Chemical 0
, O 0
0 O 0
. O 0
1 O 0
mg O 0
/ O 0
kg O 0
, O 0
plus O 0
placebo O 0
; O 0
and O 0
group O 0
4 O 0
- O 0
- O 0
cimetidine B-Chemical 0
plus O 0
chlorpheniramine B-Chemical 0
. O 0

Histamine B-Chemical 0
release O 0
occurred O 0
in O 0
most O 0
patients O 0
, O 0
the O 0
highest O 0
level O 0
2 O 0
minutes O 0
after O 0
d B-Chemical 0
- I-Chemical 0
tubocurarine I-Chemical 0
dosing O 0
. O 0

Group O 0
1 O 0
had O 0
a O 0
moderate O 0
negative O 0
correlation O 0
between O 0
plasma O 0
histamine B-Chemical 0
change O 0
and O 0
systemic O 0
vascular O 0
resistance O 0
( O 0
r O 0
= O 0
0 O 0
. O 0
58 O 0
; O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
not O 0
present O 0
in O 0
group O 0
4 O 0
. O 0

Prior O 0
dosing O 0
with O 0
antagonists O 0
partially O 0
prevented O 0
the O 0
fall O 0
in O 0
systemic O 0
vascular O 0
resistance O 0
. O 0

These O 0
data O 0
demonstrate O 0
that O 0
the O 0
hemodynamic O 0
changes O 0
associated O 0
with O 0
d B-Chemical 0
- I-Chemical 0
tubocurarine I-Chemical 0
dosing O 0
are O 0
only O 0
partially O 0
explained O 0
by O 0
histamine B-Chemical 0
release O 0
. O 0

Thus O 0
prior O 0
dosing O 0
with O 0
H1 O 0
- O 0
and O 0
H2 O 0
- O 0
antagonists O 0
provides O 0
only O 0
partial O 0
protection O 0
. O 0

Cholecystokinin B-Chemical 0
- I-Chemical 0
octapeptide I-Chemical 0
restored O 0
morphine B-Chemical 0
- O 0
induced O 0
hippocampal O 0
long O 0
- O 0
term O 0
potentiation O 0
impairment O 0
in O 0
rats O 0
. O 0

Cholecystokinin B-Chemical 0
- I-Chemical 0
octapeptide I-Chemical 0
( O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
) O 0
, O 0
which O 0
is O 0
a O 0
typical O 0
brain O 0
- O 0
gut O 0
peptide O 0
, O 0
exerts O 0
a O 0
wide O 0
range O 0
of O 0
biological O 0
activities O 0
on O 0
the O 0
central O 0
nervous O 0
system O 0
. O 0

We O 0
have O 0
previously O 0
reported O 0
that O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
significantly O 0
alleviated O 0
morphine B-Chemical 0
- O 0
induced O 0
amnesia B-Disease 0
and O 0
reversed O 0
spine O 0
density O 0
decreases O 0
in O 0
the O 0
CA1 O 0
region O 0
of O 0
the O 0
hippocampus O 0
in O 0
morphine B-Chemical 0
- O 0
treated O 0
animals O 0
. O 0

Here O 0
, O 0
we O 0
investigated O 0
the O 0
effects O 0
of O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
on O 0
long O 0
- O 0
term O 0
potentiation O 0
( O 0
LTP O 0
) O 0
in O 0
the O 0
lateral O 0
perforant O 0
path O 0
( O 0
LPP O 0
) O 0
- O 0
granule O 0
cell O 0
synapse O 0
of O 0
rat O 0
dentate O 0
gyrus O 0
( O 0
DG O 0
) O 0
in O 0
acute O 0
saline O 0
or O 0
morphine B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

Population O 0
spikes O 0
( O 0
PS O 0
) O 0
, O 0
which O 0
were O 0
evoked O 0
by O 0
stimulation O 0
of O 0
the O 0
LPP O 0
, O 0
were O 0
recorded O 0
in O 0
the O 0
DG O 0
region O 0
. O 0

Acute O 0
morphine B-Chemical 0
( O 0
30mg O 0
/ O 0
kg O 0
, O 0
s O 0
. O 0
c O 0
. O 0
) O 0
treatment O 0
significantly O 0
attenuated O 0
hippocampal O 0
LTP O 0
and O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
( O 0
1ug O 0
, O 0
i O 0
. O 0
c O 0
. O 0
v O 0
. O 0
) O 0
restored O 0
the O 0
amplitude O 0
of O 0
PS O 0
that O 0
was O 0
attenuated O 0
by O 0
morphine B-Chemical 0
injection O 0
. O 0

Furthermore O 0
, O 0
microinjection O 0
of O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
and O 0
1ug O 0
, O 0
i O 0
. O 0
c O 0
. O 0
v O 0
. O 0
) O 0
also O 0
significantly O 0
augmented O 0
hippocampal O 0
LTP O 0
in O 0
saline O 0
- O 0
treated O 0
( O 0
1ml O 0
/ O 0
kg O 0
, O 0
s O 0
. O 0
c O 0
. O 0
) O 0
rats O 0
. O 0

Pre O 0
- O 0
treatment O 0
of O 0
the O 0
CCK2 O 0
receptor O 0
antagonist O 0
L O 0
- O 0
365 O 0
, O 0
260 O 0
( O 0
10ug O 0
, O 0
i O 0
. O 0
c O 0
. O 0
v O 0
) O 0
reversed O 0
the O 0
effects O 0
of O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
, O 0
but O 0
the O 0
CCK1 O 0
receptor O 0
antagonist O 0
L O 0
- O 0
364 O 0
, O 0
718 O 0
( O 0
10ug O 0
, O 0
i O 0
. O 0
c O 0
. O 0
v O 0
) O 0
did O 0
not O 0
. O 0

The O 0
present O 0
results O 0
demonstrate O 0
that O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
attenuates O 0
the O 0
effect O 0
of O 0
morphine B-Chemical 0
on O 0
hippocampal O 0
LTP O 0
through O 0
CCK2 O 0
receptors O 0
and O 0
suggest O 0
an O 0
ameliorative O 0
function O 0
of O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
on O 0
morphine B-Chemical 0
- O 0
induced O 0
memory B-Disease 0
impairment I-Disease 0
. O 0

Glial O 0
activation O 0
and O 0
post O 0
- O 0
synaptic O 0
neurotoxicity B-Disease 0
: O 0
the O 0
key O 0
events O 0
in O 0
Streptozotocin B-Chemical 0
( O 0
ICV O 0
) O 0
induced O 0
memory B-Disease 0
impairment I-Disease 0
in O 0
rats O 0
. O 0

In O 0
the O 0
present O 0
study O 0
the O 0
role O 0
of O 0
glial O 0
activation O 0
and O 0
post O 0
synaptic O 0
toxicity B-Disease 0
in O 0
ICV O 0
Streptozotocin B-Chemical 0
( O 0
STZ B-Chemical 0
) O 0
induced O 0
memory B-Disease 0
impaired I-Disease 0
rats O 0
was O 0
explored O 0
. O 0

In O 0
experiment O 0
set O 0
up O 0
1 O 0
: O 0
Memory B-Disease 0
deficit I-Disease 0
was O 0
found O 0
in O 0
Morris O 0
water O 0
maze O 0
test O 0
on O 0
14 O 0
- O 0
16 O 0
days O 0
after O 0
STZ B-Chemical 0
( O 0
ICV O 0
; O 0
3mg O 0
/ O 0
Kg O 0
) O 0
administration O 0
. O 0

STZ B-Chemical 0
causes O 0
increased O 0
expression O 0
of O 0
GFAP O 0
, O 0
CD11b O 0
and O 0
TNF O 0
- O 0
a O 0
indicating O 0
glial O 0
activation O 0
and O 0
neuroinflammation B-Disease 0
. O 0

STZ B-Chemical 0
also O 0
significantly O 0
increased O 0
the O 0
level O 0
of O 0
ROS O 0
, O 0
nitrite B-Chemical 0
, O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
and O 0
reduced O 0
the O 0
mitochondrial O 0
activity O 0
in O 0
synaptosomal O 0
preparation O 0
illustrating O 0
free O 0
radical O 0
generation O 0
and O 0
excitotoxicity B-Disease 0
. O 0

Increased O 0
expression O 0
and O 0
activity O 0
of O 0
Caspase O 0
- O 0
3 O 0
was O 0
also O 0
observed O 0
in O 0
STZ B-Chemical 0
treated O 0
rat O 0
which O 0
specify O 0
apoptotic O 0
cell O 0
death O 0
in O 0
hippocampus O 0
and O 0
cortex O 0
. O 0

STZ B-Chemical 0
treatment O 0
showed O 0
decrease O 0
expression O 0
of O 0
post O 0
synaptic O 0
markers O 0
CaMKIIa O 0
and O 0
PSD O 0
- O 0
95 O 0
, O 0
while O 0
, O 0
expression O 0
of O 0
pre O 0
synaptic O 0
markers O 0
( O 0
synaptophysin O 0
and O 0
SNAP O 0
- O 0
25 O 0
) O 0
remains O 0
unaltered O 0
indicating O 0
selective O 0
post O 0
synaptic O 0
neurotoxicity B-Disease 0
. O 0

Oral O 0
treatment O 0
with O 0
Memantine B-Chemical 0
( O 0
10mg O 0
/ O 0
kg O 0
) O 0
and O 0
Ibuprofen B-Chemical 0
( O 0
50 O 0
mg O 0
/ O 0
kg O 0
) O 0
daily O 0
for O 0
13 O 0
days O 0
attenuated O 0
STZ B-Chemical 0
induced O 0
glial O 0
activation O 0
, O 0
apoptotic O 0
cell O 0
death O 0
and O 0
post O 0
synaptic O 0
neurotoxicity B-Disease 0
in O 0
rat O 0
brain O 0
. O 0

Further O 0
, O 0
in O 0
experiment O 0
set O 0
up O 0
2 O 0
: O 0
where O 0
memory O 0
function O 0
was O 0
not O 0
affected O 0
i O 0
. O 0
e O 0
. O 0
7 O 0
- O 0
9 O 0
days O 0
after O 0
STZ B-Chemical 0
treatment O 0
. O 0

The O 0
level O 0
of O 0
GFAP O 0
, O 0
CD11b O 0
, O 0
TNF O 0
- O 0
a O 0
, O 0
ROS O 0
and O 0
nitrite B-Chemical 0
levels O 0
were O 0
increased O 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
apoptotic O 0
marker O 0
, O 0
synaptic O 0
markers O 0
, O 0
mitochondrial O 0
activity O 0
and O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
levels O 0
remained O 0
unaffected O 0
. O 0

Collective O 0
data O 0
indicates O 0
that O 0
neuroinflammatory B-Disease 0
process O 0
and O 0
oxidative O 0
stress O 0
occurs O 0
earlier O 0
to O 0
apoptosis O 0
and O 0
does O 0
not O 0
affect O 0
memory O 0
function O 0
. O 0

Present O 0
study O 0
clearly O 0
suggests O 0
that O 0
glial O 0
activation O 0
and O 0
post O 0
synaptic O 0
neurotoxicity B-Disease 0
are O 0
the O 0
key O 0
factors O 0
in O 0
STZ B-Chemical 0
induced O 0
memory B-Disease 0
impairment I-Disease 0
and O 0
neuronal O 0
cell O 0
death O 0
. O 0

Comparison O 0
of O 0
effects O 0
of O 0
isotonic O 0
sodium B-Chemical 0
chloride I-Chemical 0
with O 0
diltiazem B-Chemical 0
in O 0
prevention O 0
of O 0
contrast B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
. O 0

INTRODUCTION O 0
AND O 0
OBJECTIVE O 0
: O 0
Contrast B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
( O 0
CIN O 0
) O 0
significantly O 0
increases O 0
the O 0
morbidity O 0
and O 0
mortality O 0
of O 0
patients O 0
. O 0

The O 0
aim O 0
of O 0
this O 0
study O 0
is O 0
to O 0
investigate O 0
and O 0
compare O 0
the O 0
protective O 0
effects O 0
of O 0
isotonic O 0
sodium B-Chemical 0
chloride I-Chemical 0
with O 0
sodium B-Chemical 0
bicarbonate I-Chemical 0
infusion O 0
and O 0
isotonic O 0
sodium B-Chemical 0
chloride I-Chemical 0
infusion O 0
with O 0
diltiazem B-Chemical 0
, O 0
a O 0
calcium B-Chemical 0
channel O 0
blocker O 0
, O 0
in O 0
preventing O 0
CIN O 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
Our O 0
study O 0
included O 0
patients O 0
who O 0
were O 0
administered O 0
30 O 0
- O 0
60 O 0
mL O 0
of O 0
iodinated O 0
contrast B-Chemical 0
agent O 0
for O 0
percutaneous O 0
coronary O 0
angiography O 0
( O 0
PCAG O 0
) O 0
, O 0
all O 0
with O 0
creatinine B-Chemical 0
values O 0
between O 0
1 O 0
. O 0
1 O 0
and O 0
3 O 0
. O 0
1 O 0
mg O 0
/ O 0
dL O 0
. O 0

Patients O 0
were O 0
divided O 0
into O 0
three O 0
groups O 0
and O 0
each O 0
group O 0
had O 0
20 O 0
patients O 0
. O 0

The O 0
first O 0
group O 0
of O 0
patients O 0
was O 0
administered O 0
isotonic O 0
sodium B-Chemical 0
chloride I-Chemical 0
; O 0
the O 0
second O 0
group O 0
was O 0
administered O 0
a O 0
solution O 0
that O 0
of O 0
5 O 0
% O 0
dextrose B-Chemical 0
and O 0
sodium B-Chemical 0
bicarbonate I-Chemical 0
, O 0
while O 0
the O 0
third O 0
group O 0
was O 0
administered O 0
isotonic O 0
sodium B-Chemical 0
chloride I-Chemical 0
before O 0
and O 0
after O 0
the O 0
contrast B-Chemical 0
injection O 0
. O 0

The O 0
third O 0
group O 0
received O 0
an O 0
additional O 0
injection O 0
of O 0
diltiazem B-Chemical 0
the O 0
day O 0
before O 0
and O 0
first O 0
2 O 0
days O 0
after O 0
the O 0
contrast B-Chemical 0
injection O 0
. O 0

All O 0
of O 0
the O 0
patients O 0
' O 0
plasma O 0
blood B-Chemical 0
urea I-Chemical 0
nitrogen I-Chemical 0
( O 0
BUN B-Chemical 0
) O 0
and O 0
creatinine B-Chemical 0
levels O 0
were O 0
measured O 0
on O 0
the O 0
second O 0
and O 0
seventh O 0
day O 0
after O 0
the O 0
administration O 0
of O 0
intravenous O 0
contrast B-Chemical 0
material O 0
. O 0

RESULTS O 0
: O 0
The O 0
basal O 0
creatinine B-Chemical 0
levels O 0
were O 0
similar O 0
for O 0
all O 0
three O 0
groups O 0
( O 0
p O 0
> O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Among O 0
a O 0
total O 0
of O 0
60 O 0
patients O 0
included O 0
in O 0
the O 0
study O 0
, O 0
16 O 0
patients O 0
developed O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
( O 0
ARF B-Disease 0
) O 0
on O 0
the O 0
second O 0
day O 0
after O 0
contrast B-Chemical 0
material O 0
was O 0
injected O 0
( O 0
26 O 0
. O 0
6 O 0
% O 0
) O 0
. O 0

The O 0
number O 0
of O 0
patients O 0
who O 0
developed O 0
ARF B-Disease 0
on O 0
the O 0
second O 0
day O 0
after O 0
the O 0
injection O 0
in O 0
the O 0
first O 0
group O 0
was O 0
five O 0
( O 0
25 O 0
% O 0
) O 0
, O 0
in O 0
the O 0
second O 0
group O 0
was O 0
six O 0
( O 0
30 O 0
% O 0
) O 0
and O 0
the O 0
third O 0
group O 0
was O 0
five O 0
( O 0
25 O 0
% O 0
) O 0
( O 0
p O 0
> O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
There O 0
was O 0
no O 0
significant O 0
difference O 0
between O 0
isotonic O 0
sodium B-Chemical 0
chloride I-Chemical 0
, O 0
sodium B-Chemical 0
bicarbonate I-Chemical 0
and O 0
isotonic O 0
sodium B-Chemical 0
chloride I-Chemical 0
with O 0
diltiazem B-Chemical 0
application O 0
in O 0
prevention O 0
of O 0
CIN O 0
. O 0

Neurocognitive O 0
and O 0
neuroradiologic O 0
central O 0
nervous O 0
system O 0
late O 0
effects O 0
in O 0
children O 0
treated O 0
on O 0
Pediatric O 0
Oncology O 0
Group O 0
( O 0
POG O 0
) O 0
P9605 O 0
( O 0
standard O 0
risk O 0
) O 0
and O 0
P9201 O 0
( O 0
lesser O 0
risk O 0
) O 0
acute B-Disease 0
lymphoblastic I-Disease 0
leukemia I-Disease 0
protocols O 0
( O 0
ACCL0131 O 0
) O 0
: O 0
a O 0
methotrexate B-Chemical 0
consequence O 0
? O 0

A O 0
report O 0
from O 0
the O 0
Children O 0
' O 0
s O 0
Oncology O 0
Group O 0
. O 0

Concerns O 0
about O 0
long O 0
- O 0
term O 0
methotrexate B-Chemical 0
( O 0
MTX B-Chemical 0
) O 0
neurotoxicity B-Disease 0
in O 0
the O 0
1990s O 0
led O 0
to O 0
modifications O 0
in O 0
intrathecal O 0
( O 0
IT O 0
) O 0
therapy O 0
, O 0
leucovorin O 0
rescue O 0
, O 0
and O 0
frequency O 0
of O 0
systemic O 0
MTX B-Chemical 0
administration O 0
in O 0
children O 0
with O 0
acute B-Disease 0
lymphoblastic I-Disease 0
leukemia I-Disease 0
. O 0

In O 0
this O 0
study O 0
, O 0
neurocognitive O 0
outcomes O 0
and O 0
neuroradiologic O 0
evidence O 0
of O 0
leukoencephalopathy B-Disease 0
were O 0
compared O 0
in O 0
children O 0
treated O 0
with O 0
intense O 0
central O 0
nervous O 0
system O 0
( O 0
CNS O 0
) O 0
- O 0
directed O 0
therapy O 0
( O 0
P9605 O 0
) O 0
versus O 0
those O 0
receiving O 0
fewer O 0
CNS O 0
- O 0
directed O 0
treatment O 0
days O 0
during O 0
intensive O 0
consolidation O 0
( O 0
P9201 O 0
) O 0
. O 0

A O 0
total O 0
of O 0
66 O 0
children O 0
from O 0
16 O 0
Pediatric O 0
Oncology O 0
Group O 0
institutions O 0
with O 0
" O 0
standard O 0
- O 0
risk O 0
" O 0
acute B-Disease 0
lymphoblastic I-Disease 0
leukemia I-Disease 0
, O 0
1 O 0
. O 0
00 O 0
to O 0
9 O 0
. O 0
99 O 0
years O 0
at O 0
diagnosis O 0
, O 0
without O 0
evidence O 0
of O 0
CNS O 0
leukemia B-Disease 0
at O 0
diagnosis O 0
were O 0
enrolled O 0
on O 0
ACCL0131 O 0
: O 0
28 O 0
from O 0
P9201 O 0
and O 0
38 O 0
from O 0
P9605 O 0
. O 0

Magnetic O 0
resonance O 0
imaging O 0
scans O 0
and O 0
standard O 0
neuropsychological O 0
tests O 0
were O 0
performed O 0
> O 0
2 O 0
. O 0
6 O 0
years O 0
after O 0
the O 0
end O 0
of O 0
treatment O 0
. O 0

Significantly O 0
more O 0
P9605 O 0
patients O 0
developed O 0
leukoencephalopathy B-Disease 0
compared O 0
with O 0
P9201 O 0
patients O 0
( O 0
68 O 0
% O 0
, O 0
95 O 0
% O 0
confidence O 0
interval O 0
49 O 0
% O 0
- O 0
83 O 0
% O 0
vs O 0
. O 0
22 O 0
% O 0
, O 0
95 O 0
% O 0
confidence O 0
interval O 0
5 O 0
% O 0
- O 0
44 O 0
% O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
001 O 0
) O 0
identified O 0
as O 0
late O 0
as O 0
7 O 0
. O 0
7 O 0
years O 0
after O 0
the O 0
end O 0
of O 0
treatment O 0
. O 0

Overall O 0
, O 0
40 O 0
% O 0
of O 0
patients O 0
scored O 0
< O 0
85 O 0
on O 0
either O 0
Verbal O 0
or O 0
Performance O 0
IQ O 0
. O 0

Children O 0
on O 0
both O 0
studies O 0
had O 0
significant O 0
attention B-Disease 0
problems I-Disease 0
, O 0
but O 0
P9605 O 0
children O 0
scored O 0
below O 0
average O 0
on O 0
more O 0
neurocognitive O 0
measures O 0
than O 0
those O 0
treated O 0
on O 0
P9201 O 0
( O 0
82 O 0
% O 0
, O 0
14 O 0
/ O 0
17 O 0
measures O 0
vs O 0
. O 0
24 O 0
% O 0
, O 0
4 O 0
/ O 0
17 O 0
measures O 0
) O 0
. O 0

This O 0
supports O 0
ongoing O 0
concerns O 0
about O 0
intensive O 0
MTX B-Chemical 0
exposure O 0
as O 0
a O 0
major O 0
contributor O 0
to O 0
CNS O 0
late O 0
effects O 0
. O 0

Tranexamic B-Chemical 0
acid I-Chemical 0
overdosage O 0
- O 0
induced O 0
generalized O 0
seizure B-Disease 0
in O 0
renal B-Disease 0
failure I-Disease 0
. O 0

We O 0
report O 0
a O 0
45 O 0
- O 0
year O 0
- O 0
old O 0
lady O 0
with O 0
chronic B-Disease 0
kidney I-Disease 0
disease I-Disease 0
stage O 0
4 O 0
due O 0
to O 0
chronic O 0
tubulointerstial B-Disease 0
disease I-Disease 0
. O 0

She O 0
was O 0
admitted O 0
to O 0
our O 0
center O 0
for O 0
severe O 0
anemia B-Disease 0
due O 0
to O 0
menorrhagia B-Disease 0
and O 0
deterioration B-Disease 0
of I-Disease 0
renal I-Disease 0
function I-Disease 0
. O 0

She O 0
was O 0
infused O 0
three O 0
units O 0
of O 0
packed O 0
cells O 0
during O 0
a O 0
session O 0
of O 0
hemodialysis O 0
. O 0

Tranexamic B-Chemical 0
acid I-Chemical 0
( O 0
TNA B-Chemical 0
) O 0
1 O 0
g O 0
8 O 0
- O 0
hourly O 0
was O 0
administered O 0
to O 0
her O 0
to O 0
control O 0
bleeding B-Disease 0
per O 0
vaginum O 0
. O 0

Two O 0
hours O 0
after O 0
the O 0
sixth O 0
dose O 0
of O 0
TNA B-Chemical 0
, O 0
she O 0
had O 0
an O 0
episode O 0
of O 0
generalized O 0
tonic B-Disease 0
clonic I-Disease 0
convulsions I-Disease 0
. O 0

TNA B-Chemical 0
was O 0
discontinued O 0
. O 0

Investigations O 0
of O 0
the O 0
patient O 0
revealed O 0
no O 0
biochemical O 0
or O 0
structural O 0
central O 0
nervous B-Disease 0
system I-Disease 0
abnormalities I-Disease 0
that O 0
could O 0
have O 0
provoked O 0
the O 0
convulsions B-Disease 0
. O 0

She O 0
did O 0
not O 0
require O 0
any O 0
further O 0
dialytic O 0
support O 0
. O 0

She O 0
had O 0
no O 0
further O 0
episodes O 0
of O 0
convulsion B-Disease 0
till O 0
dis O 0
- O 0
charge O 0
and O 0
during O 0
the O 0
two O 0
months O 0
of O 0
follow O 0
- O 0
up O 0
. O 0

Thus O 0
, O 0
the O 0
precipitating O 0
cause O 0
of O 0
convulsions B-Disease 0
was O 0
believed O 0
to O 0
be O 0
an O 0
overdose B-Disease 0
of O 0
TNA B-Chemical 0
. O 0

Pre O 0
- O 0
treatment O 0
of O 0
bupivacaine B-Chemical 0
- O 0
induced O 0
cardiovascular B-Disease 0
depression I-Disease 0
using O 0
different O 0
lipid O 0
formulations O 0
of O 0
propofol B-Chemical 0
. O 0

BACKGROUND O 0
: O 0
Pre O 0
- O 0
treatment O 0
with O 0
lipid O 0
emulsions O 0
has O 0
been O 0
shown O 0
to O 0
increase O 0
lethal O 0
doses O 0
of O 0
bupivacaine B-Chemical 0
, O 0
and O 0
the O 0
lipid O 0
content O 0
of O 0
propofol B-Chemical 0
may O 0
alleviate O 0
bupivacaine B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

The O 0
aim O 0
of O 0
this O 0
study O 0
is O 0
to O 0
investigate O 0
the O 0
effects O 0
of O 0
propofol B-Chemical 0
in O 0
intralipid O 0
or O 0
medialipid O 0
emulsions O 0
on O 0
bupivacaine B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

METHODS O 0
: O 0
Rats O 0
were O 0
anaesthetised O 0
with O 0
ketamine B-Chemical 0
and O 0
were O 0
given O 0
0 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
/ O 0
min O 0
propofol B-Chemical 0
in O 0
intralipid O 0
( O 0
Group O 0
P O 0
) O 0
, O 0
propofol B-Chemical 0
in O 0
medialipid O 0
( O 0
Group O 0
L O 0
) O 0
, O 0
or O 0
saline O 0
( O 0
Group O 0
C O 0
) O 0
over O 0
20 O 0
min O 0
. O 0

Thereafter O 0
, O 0
2 O 0
mg O 0
/ O 0
kg O 0
/ O 0
min O 0
bupivacaine B-Chemical 0
0 O 0
. O 0
5 O 0
% O 0
was O 0
infused O 0
. O 0

We O 0
recorded O 0
time O 0
to O 0
first O 0
dysrhythmia B-Disease 0
occurrence O 0
, O 0
respective O 0
times O 0
to O 0
25 O 0
% O 0
and O 0
50 O 0
% O 0
reduction O 0
of O 0
the O 0
heart O 0
rate O 0
( O 0
HR O 0
) O 0
and O 0
mean O 0
arterial O 0
pressure O 0
, O 0
and O 0
time O 0
to O 0
asystole B-Disease 0
and O 0
total O 0
amount O 0
of O 0
bupivacaine B-Chemical 0
consumption O 0
. O 0

Blood O 0
and O 0
tissue O 0
samples O 0
were O 0
collected O 0
following O 0
asystole B-Disease 0
. O 0

RESULTS O 0
: O 0
The O 0
time O 0
to O 0
first O 0
dysrhythmia B-Disease 0
occurrence O 0
, O 0
time O 0
to O 0
25 O 0
% O 0
and O 0
50 O 0
% O 0
reductions O 0
in O 0
HR O 0
, O 0
and O 0
time O 0
to O 0
asystole B-Disease 0
were O 0
longer O 0
in O 0
Group O 0
P O 0
than O 0
the O 0
other O 0
groups O 0
. O 0

The O 0
cumulative O 0
bupivacaine B-Chemical 0
dose O 0
given O 0
at O 0
those O 0
time O 0
points O 0
was O 0
higher O 0
in O 0
Group O 0
P O 0
. O 0
Plasma O 0
bupivacaine B-Chemical 0
levels O 0
were O 0
significantly O 0
lower O 0
in O 0
Group O 0
P O 0
than O 0
in O 0
Group O 0
C O 0
. O 0
Bupivacaine B-Chemical 0
levels O 0
in O 0
the O 0
brain O 0
and O 0
heart O 0
were O 0
significantly O 0
lower O 0
in O 0
Group O 0
P O 0
and O 0
Group O 0
L O 0
than O 0
in O 0
Group O 0
C O 0
. O 0

CONCLUSION O 0
: O 0
We O 0
conclude O 0
that O 0
pre O 0
- O 0
treatment O 0
with O 0
propofol B-Chemical 0
in O 0
intralipid O 0
, O 0
compared O 0
with O 0
propofol B-Chemical 0
in O 0
medialipid O 0
or O 0
saline O 0
, O 0
delayed O 0
the O 0
onset O 0
of O 0
bupivacaine B-Chemical 0
- O 0
induced O 0
cardiotoxic B-Disease 0
effects O 0
as O 0
well O 0
as O 0
reduced O 0
plasma O 0
bupivacaine B-Chemical 0
levels O 0
. O 0

Further O 0
studies O 0
are O 0
needed O 0
to O 0
explore O 0
tissue O 0
bupivacaine B-Chemical 0
levels O 0
of O 0
propofol B-Chemical 0
in O 0
medialipid O 0
and O 0
adapt O 0
these O 0
results O 0
to O 0
clinical O 0
practice O 0
. O 0

Drug B-Disease 0
- I-Disease 0
Induced I-Disease 0
Acute I-Disease 0
Liver I-Disease 0
Injury I-Disease 0
Within O 0
12 O 0
Hours O 0
After O 0
Fluvastatin B-Chemical 0
Therapy O 0
. O 0

Although O 0
statins B-Chemical 0
are O 0
generally O 0
well O 0
- O 0
tolerated O 0
drugs O 0
, O 0
recent O 0
cases O 0
of O 0
drug B-Disease 0
- I-Disease 0
induced I-Disease 0
liver I-Disease 0
injury I-Disease 0
associated O 0
with O 0
their O 0
use O 0
have O 0
been O 0
reported O 0
. O 0

A O 0
52 O 0
- O 0
year O 0
- O 0
old O 0
Chinese O 0
man O 0
reported O 0
with O 0
liver B-Disease 0
damage I-Disease 0
, O 0
which O 0
appeared O 0
12 O 0
hours O 0
after O 0
beginning O 0
treatment O 0
with O 0
fluvastatin B-Chemical 0
. O 0

Patient O 0
presented O 0
with O 0
complaints O 0
of O 0
increasing O 0
nausea B-Disease 0
, O 0
anorexia B-Disease 0
, O 0
and O 0
upper O 0
abdominal B-Disease 0
pain I-Disease 0
. O 0

His O 0
laboratory O 0
values O 0
showed O 0
elevated O 0
creatine B-Chemical 0
kinase O 0
and O 0
transaminases O 0
. O 0

Testing O 0
for O 0
autoantibodies O 0
was O 0
also O 0
negative O 0
. O 0

The O 0
liver O 0
biochemistries O 0
eventually O 0
normalized O 0
within O 0
3 O 0
weeks O 0
of O 0
stopping O 0
the O 0
fluvastatin B-Chemical 0
. O 0

Therefore O 0
, O 0
when O 0
prescribing O 0
statins O 0
, O 0
the O 0
possibility O 0
of O 0
hepatic B-Disease 0
damage I-Disease 0
should O 0
be O 0
taken O 0
into O 0
account O 0
. O 0

Fluconazole B-Chemical 0
associated O 0
agranulocytosis B-Disease 0
and O 0
thrombocytopenia B-Disease 0
. O 0

CASE O 0
: O 0
We O 0
describe O 0
a O 0
second O 0
case O 0
of O 0
fluconazole B-Chemical 0
associated O 0
agranulocytosis B-Disease 0
with O 0
thrombocytopenia B-Disease 0
and O 0
recovery O 0
upon O 0
discontinuation O 0
of O 0
therapy O 0
. O 0

The O 0
patient O 0
began O 0
to O 0
have O 0
changes O 0
in O 0
white O 0
blood O 0
cells O 0
and O 0
platelets O 0
within O 0
48 O 0
h O 0
of O 0
administration O 0
of O 0
fluconazole B-Chemical 0
and O 0
began O 0
to O 0
recover O 0
with O 0
48 O 0
h O 0
of O 0
discontinuation O 0
. O 0

This O 0
case O 0
highlights O 0
that O 0
drug O 0
- O 0
induced O 0
blood B-Disease 0
dyscrasias I-Disease 0
can O 0
occur O 0
unexpectedly O 0
as O 0
a O 0
result O 0
of O 0
treatment O 0
with O 0
a O 0
commonly O 0
used O 0
drug O 0
thought O 0
to O 0
be O 0
" O 0
safe O 0
" O 0
. O 0

CONCLUSION O 0
: O 0
According O 0
to O 0
Naranjo O 0
' O 0
s O 0
algorithm O 0
the O 0
likelihood O 0
that O 0
our O 0
patient O 0
' O 0
s O 0
agranulocytosis B-Disease 0
and O 0
thrombocytopenia B-Disease 0
occurred O 0
as O 0
a O 0
result O 0
of O 0
therapy O 0
with O 0
fluconazole B-Chemical 0
is O 0
probable O 0
, O 0
with O 0
a O 0
total O 0
of O 0
six O 0
points O 0
. O 0

We O 0
feel O 0
that O 0
the O 0
weight O 0
of O 0
the O 0
overall O 0
evidence O 0
of O 0
this O 0
evidence O 0
is O 0
strong O 0
. O 0

In O 0
particular O 0
the O 0
temporal O 0
relationship O 0
of O 0
bone B-Disease 0
marrow I-Disease 0
suppression I-Disease 0
to O 0
the O 0
initiation O 0
of O 0
fluconazole B-Chemical 0
and O 0
the O 0
abatement O 0
of O 0
symptoms O 0
that O 0
rapidly O 0
reversed O 0
immediately O 0
following O 0
discontinuation O 0
. O 0

Two O 0
- O 0
dimensional O 0
speckle O 0
tracking O 0
echocardiography O 0
combined O 0
with O 0
high O 0
- O 0
sensitive O 0
cardiac O 0
troponin O 0
T O 0
in O 0
early O 0
detection O 0
and O 0
prediction O 0
of O 0
cardiotoxicity B-Disease 0
during O 0
epirubicine B-Chemical 0
- O 0
based O 0
chemotherapy O 0
. O 0

AIMS O 0
: O 0
To O 0
investigate O 0
whether O 0
alterations O 0
of O 0
myocardial B-Disease 0
strain I-Disease 0
and O 0
high O 0
- O 0
sensitive O 0
cardiac O 0
troponin O 0
T O 0
( O 0
cTnT O 0
) O 0
could O 0
predict O 0
future O 0
cardiac B-Disease 0
dysfunction I-Disease 0
in O 0
patients O 0
after O 0
epirubicin B-Chemical 0
exposure O 0
. O 0

METHODS O 0
: O 0
Seventy O 0
- O 0
five O 0
patients O 0
with O 0
non B-Disease 0
- I-Disease 0
Hodgkin I-Disease 0
lymphoma I-Disease 0
treated O 0
with O 0
epirubicin B-Chemical 0
were O 0
studied O 0
. O 0

Blood O 0
collection O 0
and O 0
echocardiography O 0
were O 0
performed O 0
at O 0
baseline O 0
, O 0
1 O 0
day O 0
after O 0
the O 0
third O 0
cycle O 0
, O 0
and O 0
1 O 0
day O 0
after O 0
completion O 0
of O 0
chemotherapy O 0
. O 0

Patients O 0
were O 0
studied O 0
using O 0
echocardiography O 0
during O 0
follow O 0
- O 0
up O 0
. O 0

Global O 0
longitudinal O 0
( O 0
GLS O 0
) O 0
, O 0
circumferential O 0
( O 0
GCS O 0
) O 0
, O 0
and O 0
radial O 0
strain O 0
( O 0
GRS O 0
) O 0
were O 0
calculated O 0
using O 0
speckle O 0
tracking O 0
echocardiography O 0
. O 0

Left O 0
ventricular O 0
ejection O 0
fraction O 0
was O 0
analysed O 0
by O 0
real O 0
- O 0
time O 0
3D O 0
echocardiography O 0
. O 0

Cardiotoxicity B-Disease 0
was O 0
defined O 0
as O 0
a O 0
reduction O 0
of O 0
the O 0
LVEF O 0
of O 0
> O 0
5 O 0
% O 0
to O 0
< O 0
55 O 0
% O 0
with O 0
symptoms O 0
of O 0
heart B-Disease 0
failure I-Disease 0
or O 0
an O 0
asymptomatic O 0
reduction O 0
of O 0
the O 0
LVEF O 0
of O 0
> O 0
10 O 0
% O 0
to O 0
< O 0
55 O 0
% O 0
. O 0

RESULTS O 0
: O 0
Fourteen O 0
patients O 0
( O 0
18 O 0
. O 0
67 O 0
% O 0
) O 0
developed O 0
cardiotoxicity B-Disease 0
after O 0
treatment O 0
. O 0

GLS O 0
( O 0
- O 0
18 O 0
. O 0
48 O 0
+ O 0
1 O 0
. O 0
72 O 0
% O 0
vs O 0
. O 0
- O 0
15 O 0
. O 0
96 O 0
+ O 0
1 O 0
. O 0
6 O 0
% O 0
) O 0
, O 0
GCS O 0
( O 0
- O 0
20 O 0
. O 0
93 O 0
+ O 0
2 O 0
. O 0
86 O 0
% O 0
vs O 0
. O 0
- O 0
19 O 0
. O 0
20 O 0
+ O 0
3 O 0
. O 0
21 O 0
% O 0
) O 0
, O 0
and O 0
GRS O 0
( O 0
39 O 0
. O 0
23 O 0
+ O 0
6 O 0
. O 0
44 O 0
% O 0
vs O 0
. O 0
34 O 0
. O 0
98 O 0
+ O 0
6 O 0
. O 0
2 O 0
% O 0
) O 0
were O 0
markedly O 0
reduced O 0
and O 0
cTnT O 0
was O 0
elevated O 0
from O 0
0 O 0
. O 0
0010 O 0
+ O 0
0 O 0
. O 0
0020 O 0
to O 0
0 O 0
. O 0
0073 O 0
+ O 0
0 O 0
. O 0
0038 O 0
ng O 0
/ O 0
mL O 0
( O 0
P O 0
all O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
at O 0
the O 0
completion O 0
of O 0
chemotherapy O 0
compared O 0
with O 0
baseline O 0
values O 0
. O 0

A O 0
> O 0
15 O 0
. O 0
9 O 0
% O 0
decrease O 0
in O 0
GLS O 0
[ O 0
sensitivity O 0
, O 0
86 O 0
% O 0
; O 0
specificity O 0
, O 0
75 O 0
% O 0
; O 0
area O 0
under O 0
the O 0
curve O 0
( O 0
AUC O 0
) O 0
= O 0
0 O 0
. O 0
815 O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
001 O 0
] O 0
and O 0
a O 0
> O 0
0 O 0
. O 0
004 O 0
ng O 0
/ O 0
mL O 0
elevation O 0
in O 0
cTnT O 0
( O 0
sensitivity O 0
, O 0
79 O 0
% O 0
; O 0
specificity O 0
, O 0
64 O 0
% O 0
; O 0
AUC O 0
= O 0
0 O 0
. O 0
757 O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
005 O 0
) O 0
from O 0
baseline O 0
to O 0
the O 0
third O 0
cycle O 0
of O 0
chemotherapy O 0
predicted O 0
later O 0
cardiotoxicity B-Disease 0
. O 0

The O 0
decrease O 0
in O 0
GLS O 0
remained O 0
the O 0
only O 0
independent O 0
predictor O 0
of O 0
cardiotoxicity B-Disease 0
( O 0
P O 0
= O 0
0 O 0
. O 0
000 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
GLS O 0
combined O 0
with O 0
cTnT O 0
may O 0
provide O 0
a O 0
reliable O 0
and O 0
non O 0
- O 0
invasive O 0
method O 0
to O 0
predict O 0
cardiac B-Disease 0
dysfunction I-Disease 0
in O 0
patients O 0
receiving O 0
anthracycline B-Chemical 0
- O 0
based O 0
chemotherapy O 0
. O 0

Prevention O 0
of O 0
etomidate B-Chemical 0
- O 0
induced O 0
myoclonus B-Disease 0
: O 0
which O 0
is O 0
superior O 0
: O 0
Fentanyl B-Chemical 0
, O 0
midazolam B-Chemical 0
, O 0
or O 0
a O 0
combination O 0
? O 0

A O 0
Retrospective O 0
comparative O 0
study O 0
. O 0

BACKGROUND O 0
: O 0
In O 0
this O 0
retrospective O 0
comparative O 0
study O 0
, O 0
we O 0
aimed O 0
to O 0
compare O 0
the O 0
effectiveness O 0
of O 0
fentanyl B-Chemical 0
, O 0
midazolam B-Chemical 0
, O 0
and O 0
a O 0
combination O 0
of O 0
fentanyl B-Chemical 0
and O 0
midazolam B-Chemical 0
to O 0
prevent O 0
etomidate B-Chemical 0
- O 0
induced O 0
myoclonus B-Disease 0
. O 0

MATERIAL O 0
AND O 0
METHODS O 0
: O 0
This O 0
study O 0
was O 0
performed O 0
based O 0
on O 0
anesthesia O 0
records O 0
. O 0

Depending O 0
on O 0
the O 0
drugs O 0
that O 0
would O 0
be O 0
given O 0
before O 0
the O 0
induction O 0
of O 0
anesthesia O 0
with O 0
etomidate B-Chemical 0
, O 0
the O 0
patients O 0
were O 0
separated O 0
into O 0
4 O 0
groups O 0
: O 0
no O 0
pretreatment O 0
( O 0
Group O 0
NP O 0
) O 0
, O 0
fentanyl B-Chemical 0
1 O 0
ug O 0
. O 0
kg O 0
- O 0
1 O 0
( O 0
Group O 0
F O 0
) O 0
, O 0
midazolam B-Chemical 0
0 O 0
. O 0
03 O 0
mg O 0
. O 0
kg O 0
- O 0
1 O 0
( O 0
Group O 0
M O 0
) O 0
, O 0
and O 0
midazolam B-Chemical 0
0 O 0
. O 0
015 O 0
mg O 0
. O 0
kg O 0
- O 0
1 O 0
+ O 0
fentanyl B-Chemical 0
0 O 0
. O 0
5 O 0
ug O 0
. O 0
kg O 0
- O 0
1 O 0
( O 0
Group O 0
FM O 0
) O 0
. O 0

Patients O 0
who O 0
received O 0
the O 0
same O 0
anesthetic O 0
procedure O 0
were O 0
selected O 0
: O 0
2 O 0
minutes O 0
after O 0
intravenous O 0
injections O 0
of O 0
the O 0
pretreatment O 0
drugs O 0
, O 0
anesthesia O 0
is O 0
induced O 0
with O 0
0 O 0
. O 0
3 O 0
mg O 0
. O 0
kg O 0
- O 0
1 O 0
etomidate B-Chemical 0
injected O 0
intravenously O 0
over O 0
a O 0
period O 0
of O 0
20 O 0
- O 0
30 O 0
seconds O 0
. O 0

Myoclonic B-Disease 0
movements I-Disease 0
are O 0
evaluated O 0
, O 0
which O 0
were O 0
observed O 0
and O 0
graded O 0
according O 0
to O 0
clinical O 0
severity O 0
during O 0
the O 0
2 O 0
minutes O 0
after O 0
etomidate B-Chemical 0
injection O 0
. O 0

The O 0
severity O 0
of O 0
pain B-Disease 0
due O 0
to O 0
etomidate B-Chemical 0
injection O 0
, O 0
mean O 0
arterial O 0
pressure O 0
, O 0
heart O 0
rate O 0
, O 0
and O 0
adverse O 0
effects O 0
were O 0
also O 0
evaluated O 0
. O 0

RESULTS O 0
: O 0
Study O 0
results O 0
showed O 0
that O 0
myoclonus B-Disease 0
incidence O 0
was O 0
85 O 0
% O 0
, O 0
40 O 0
% O 0
, O 0
70 O 0
% O 0
, O 0
and O 0
25 O 0
% O 0
in O 0
Group O 0
NP O 0
, O 0
Group O 0
F O 0
, O 0
Group O 0
M O 0
, O 0
and O 0
Group O 0
FM O 0
, O 0
respectively O 0
, O 0
and O 0
were O 0
significantly O 0
lower O 0
in O 0
Group O 0
F O 0
and O 0
Group O 0
FM O 0
. O 0

CONCLUSIONS O 0
: O 0
We O 0
conclude O 0
that O 0
pretreatment O 0
with O 0
fentanyl B-Chemical 0
or O 0
combination O 0
of O 0
fentanyl B-Chemical 0
and O 0
midazolam B-Chemical 0
was O 0
effective O 0
in O 0
preventing O 0
etomidate B-Chemical 0
- O 0
induced O 0
myoclonus B-Disease 0
. O 0

Convulsant O 0
effect O 0
of O 0
lindane B-Chemical 0
and O 0
regional O 0
brain O 0
concentration O 0
of O 0
GABA B-Chemical 0
and O 0
dopamine B-Chemical 0
. O 0

Lindane B-Chemical 0
( O 0
gamma B-Chemical 0
- I-Chemical 0
hexachlorocyclohexane I-Chemical 0
) O 0
is O 0
an O 0
organochlorine O 0
insecticide O 0
with O 0
known O 0
neurotoxic B-Disease 0
effects O 0
. O 0

Its O 0
mechanism O 0
of O 0
action O 0
is O 0
not O 0
well O 0
understood O 0
although O 0
it O 0
has O 0
been O 0
proposed O 0
that O 0
lindane B-Chemical 0
acts O 0
as O 0
a O 0
non O 0
- O 0
competitive O 0
antagonist O 0
at O 0
the O 0
gamma B-Chemical 0
- I-Chemical 0
aminobutyric I-Chemical 0
acid I-Chemical 0
( O 0
GABA B-Chemical 0
) O 0
- O 0
A O 0
receptor O 0
. O 0

We O 0
studied O 0
the O 0
effect O 0
of O 0
lindane B-Chemical 0
( O 0
150 O 0
mg O 0
/ O 0
kg O 0
) O 0
on O 0
the O 0
GABAergic O 0
and O 0
dopaminergic O 0
systems O 0
by O 0
measuring O 0
the O 0
concentration O 0
of O 0
GABA B-Chemical 0
, O 0
dopamine B-Chemical 0
and O 0
its O 0
metabolites O 0
in O 0
7 O 0
brain O 0
areas O 0
at O 0
the O 0
onset O 0
of O 0
seizures B-Disease 0
. O 0

All O 0
animals O 0
suffered O 0
tonic O 0
convulsions B-Disease 0
at O 0
18 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
4 O 0
min O 0
after O 0
lindane B-Chemical 0
administration O 0
. O 0

The O 0
concentration O 0
of O 0
GABA B-Chemical 0
was O 0
only O 0
slightly O 0
but O 0
significantly O 0
decreased O 0
in O 0
the O 0
colliculi O 0
without O 0
modifications O 0
in O 0
the O 0
other O 0
areas O 0
. O 0

The O 0
concentration O 0
of O 0
dopamine B-Chemical 0
was O 0
increased O 0
in O 0
the O 0
mesencephalon O 0
and O 0
that O 0
of O 0
its O 0
metabolite O 0
DOPAC B-Chemical 0
was O 0
also O 0
increased O 0
in O 0
the O 0
mesencephalon O 0
and O 0
the O 0
striatum O 0
. O 0

Cholestatic B-Disease 0
presentation O 0
of O 0
yellow O 0
phosphorus B-Chemical 0
poisoning B-Disease 0
. O 0

Yellow O 0
phosphorus B-Chemical 0
, O 0
a O 0
component O 0
of O 0
certain O 0
pesticide O 0
pastes O 0
and O 0
fireworks O 0
, O 0
is O 0
well O 0
known O 0
to O 0
cause O 0
hepatotoxicity B-Disease 0
. O 0

Poisoning B-Disease 0
with O 0
yellow O 0
phosphorus B-Chemical 0
classically O 0
manifests O 0
with O 0
acute B-Disease 0
hepatitis I-Disease 0
leading O 0
to O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
which O 0
may O 0
need O 0
liver O 0
transplantation O 0
. O 0

We O 0
present O 0
a O 0
case O 0
of O 0
yellow O 0
phosphorus B-Chemical 0
poisoning B-Disease 0
in O 0
which O 0
a O 0
patient O 0
presented O 0
with O 0
florid O 0
clinical O 0
features O 0
of O 0
cholestasis B-Disease 0
highlighting O 0
the O 0
fact O 0
that O 0
cholestasis B-Disease 0
can O 0
rarely O 0
be O 0
a O 0
presenting O 0
feature O 0
of O 0
yellow O 0
phosphorus B-Chemical 0
hepatotoxicity B-Disease 0
. O 0

Vasovagal B-Disease 0
syncope I-Disease 0
and O 0
severe O 0
bradycardia B-Disease 0
following O 0
intranasal O 0
dexmedetomidine B-Chemical 0
for O 0
pediatric O 0
procedural O 0
sedation O 0
. O 0

We O 0
report O 0
syncope B-Disease 0
and O 0
bradycardia B-Disease 0
in O 0
an O 0
11 O 0
- O 0
year O 0
- O 0
old O 0
girl O 0
following O 0
administration O 0
of O 0
intranasal O 0
dexmedetomidine B-Chemical 0
for O 0
sedation O 0
for O 0
a O 0
voiding O 0
cystourethrogram O 0
. O 0

Following O 0
successful O 0
completion O 0
of O 0
VCUG O 0
and O 0
a O 0
60 O 0
- O 0
min O 0
recovery O 0
period O 0
, O 0
the O 0
patient O 0
' O 0
s O 0
level O 0
of O 0
consciousness O 0
and O 0
vital O 0
signs O 0
returned O 0
to O 0
presedation O 0
levels O 0
. O 0

Upon O 0
leaving O 0
the O 0
sedation O 0
area O 0
, O 0
the O 0
patient O 0
collapsed O 0
, O 0
with O 0
no O 0
apparent O 0
inciting O 0
event O 0
. O 0

The O 0
patient O 0
quickly O 0
regained O 0
consciousness O 0
and O 0
no O 0
injury O 0
occurred O 0
. O 0

The O 0
primary O 0
abnormality O 0
found O 0
was O 0
persistent O 0
bradycardia B-Disease 0
, O 0
and O 0
she O 0
was O 0
admitted O 0
to O 0
the O 0
hospital O 0
for O 0
telemetric O 0
observation O 0
. O 0

The O 0
bradycardia B-Disease 0
lasted O 0
~ O 0
2 O 0
h O 0
, O 0
and O 0
further O 0
cardiac O 0
workup O 0
revealed O 0
no O 0
underlying O 0
abnormality O 0
. O 0

Unanticipated O 0
and O 0
previously O 0
unreported O 0
outcomes O 0
may O 0
be O 0
witnessed O 0
as O 0
we O 0
expand O 0
the O 0
use O 0
of O 0
certain O 0
sedatives O 0
to O 0
alternative O 0
routes O 0
of O 0
administration O 0
. O 0

Paradoxical O 0
severe O 0
agitation B-Disease 0
induced O 0
by O 0
add O 0
- O 0
on O 0
high O 0
- O 0
doses O 0
quetiapine B-Chemical 0
in O 0
schizo B-Disease 0
- I-Disease 0
affective I-Disease 0
disorder I-Disease 0
. O 0

We O 0
report O 0
the O 0
case O 0
of O 0
a O 0
35 O 0
- O 0
year O 0
- O 0
old O 0
patient O 0
suffering O 0
from O 0
schizo B-Disease 0
- I-Disease 0
affective I-Disease 0
disorder I-Disease 0
since O 0
the O 0
age O 0
of O 0
19 O 0
years O 0
, O 0
treated O 0
by O 0
a O 0
combination O 0
of O 0
first O 0
- O 0
generation O 0
antipsychotics O 0
, O 0
zuclopenthixol B-Chemical 0
( O 0
100 O 0
mg O 0
/ O 0
day O 0
) O 0
and O 0
lithium B-Chemical 0
( O 0
1200 O 0
mg O 0
/ O 0
day O 0
) O 0
( O 0
serum O 0
lithium B-Chemical 0
= O 0
0 O 0
. O 0
85 O 0
mEq O 0
/ O 0
l O 0
) O 0
. O 0

This O 0
patient O 0
had O 0
no O 0
associated O 0
personality B-Disease 0
disorder I-Disease 0
( O 0
particularly O 0
no O 0
antisocial B-Disease 0
disorder I-Disease 0
) O 0
and O 0
no O 0
substance B-Disease 0
abuse I-Disease 0
disorder I-Disease 0
. O 0

Within O 0
the O 0
48 O 0
h O 0
following O 0
the O 0
gradual O 0
introduction O 0
of O 0
quetiapine B-Chemical 0
( O 0
up O 0
to O 0
600 O 0
mg O 0
/ O 0
day O 0
) O 0
, O 0
the O 0
patient O 0
presented O 0
severe O 0
agitation B-Disease 0
without O 0
an O 0
environmental O 0
explanation O 0
, O 0
contrasting O 0
with O 0
the O 0
absence O 0
of O 0
a O 0
history O 0
of O 0
aggressiveness B-Disease 0
or O 0
personality B-Disease 0
disorder I-Disease 0
. O 0

The O 0
diagnoses O 0
of O 0
manic B-Disease 0
shift O 0
and O 0
akathisia B-Disease 0
were O 0
dismissed O 0
. O 0

The O 0
withdrawal O 0
and O 0
the O 0
gradual O 0
reintroduction O 0
of O 0
quetiapine B-Chemical 0
2 O 0
weeks O 0
later O 0
, O 0
which O 0
led O 0
to O 0
another O 0
severe O 0
agitation B-Disease 0
, O 0
enabled O 0
us O 0
to O 0
attribute O 0
the O 0
agitation B-Disease 0
specifically O 0
to O 0
quetiapine B-Chemical 0
. O 0

Antioxidant O 0
effects O 0
of O 0
bovine O 0
lactoferrin O 0
on O 0
dexamethasone B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
in O 0
rat O 0
. O 0

Dexamethasone B-Chemical 0
- O 0
( O 0
Dex B-Chemical 0
- O 0
) O 0
induced O 0
hypertension B-Disease 0
is O 0
associated O 0
with O 0
enhanced O 0
oxidative O 0
stress O 0
. O 0

Lactoferrin O 0
( O 0
LF O 0
) O 0
is O 0
an O 0
iron B-Chemical 0
- O 0
binding O 0
glycoprotein O 0
with O 0
antihypertensive O 0
properties O 0
. O 0

In O 0
this O 0
study O 0
, O 0
we O 0
investigated O 0
the O 0
effect O 0
of O 0
chronic O 0
administration O 0
of O 0
LF O 0
on O 0
oxidative O 0
stress O 0
and O 0
hypertension B-Disease 0
upon O 0
Dex B-Chemical 0
administration O 0
. O 0

Male O 0
Wistar O 0
rats O 0
were O 0
treated O 0
by O 0
Dex B-Chemical 0
( O 0
30 O 0
u O 0
g O 0
/ O 0
kg O 0
/ O 0
day O 0
subcutaneously O 0
) O 0
or O 0
saline O 0
for O 0
14 O 0
days O 0
. O 0

Oral O 0
bovine O 0
LF O 0
( O 0
30 O 0
, O 0
100 O 0
, O 0
300 O 0
mg O 0
/ O 0
kg O 0
) O 0
was O 0
given O 0
from O 0
day O 0
8 O 0
to O 0
14 O 0
in O 0
a O 0
reversal O 0
study O 0
. O 0

In O 0
a O 0
prevention O 0
study O 0
, O 0
rats O 0
received O 0
4 O 0
days O 0
of O 0
LF O 0
treatment O 0
followed O 0
by O 0
Dex B-Chemical 0
and O 0
continued O 0
during O 0
the O 0
test O 0
period O 0
. O 0

Systolic O 0
blood O 0
pressure O 0
( O 0
SBP O 0
) O 0
was O 0
measured O 0
using O 0
tail O 0
- O 0
cuff O 0
method O 0
. O 0

Thymus O 0
weight O 0
was O 0
used O 0
as O 0
a O 0
marker O 0
of O 0
glucocorticoid O 0
activity O 0
. O 0

Plasma O 0
hydrogen B-Chemical 0
peroxide I-Chemical 0
( O 0
H2O2 B-Chemical 0
) O 0
concentration O 0
and O 0
ferric O 0
reducing O 0
antioxidant O 0
power O 0
( O 0
FRAP O 0
) O 0
value O 0
were O 0
determined O 0
. O 0

Dexamethasone B-Chemical 0
significantly O 0
increased O 0
SBP O 0
and O 0
plasma O 0
H2O2 B-Chemical 0
level O 0
and O 0
decreased O 0
thymus O 0
and O 0
body O 0
weights O 0
. O 0

LF O 0
lowered O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
and O 0
dose O 0
dependently O 0
prevented O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
Dex B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
. O 0

LF O 0
prevented O 0
body O 0
weight B-Disease 0
loss I-Disease 0
and O 0
significantly O 0
reduced O 0
the O 0
elevated O 0
plasma O 0
H2O2 B-Chemical 0
and O 0
increased O 0
FRAP O 0
values O 0
. O 0

Chronic O 0
administration O 0
of O 0
LF O 0
strongly O 0
reduced O 0
the O 0
blood O 0
pressure O 0
and O 0
production O 0
of O 0
ROS O 0
and O 0
improved O 0
antioxidant O 0
capacity O 0
in O 0
Dex B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
, O 0
suggesting O 0
the O 0
role O 0
of O 0
inhibition O 0
of O 0
oxidative O 0
stress O 0
as O 0
another O 0
mechanism O 0
of O 0
antihypertensive O 0
action O 0
of O 0
LF O 0
. O 0

The O 0
association O 0
between O 0
tranexamic B-Chemical 0
acid I-Chemical 0
and O 0
convulsive B-Disease 0
seizures B-Disease 0
after O 0
cardiac O 0
surgery O 0
: O 0
a O 0
multivariate O 0
analysis O 0
in O 0
11 O 0
529 O 0
patients O 0
. O 0

Because O 0
of O 0
a O 0
lack O 0
of O 0
contemporary O 0
data O 0
regarding O 0
seizures B-Disease 0
after O 0
cardiac O 0
surgery O 0
, O 0
we O 0
undertook O 0
a O 0
retrospective O 0
analysis O 0
of O 0
prospectively O 0
collected O 0
data O 0
from O 0
11 O 0
529 O 0
patients O 0
in O 0
whom O 0
cardiopulmonary O 0
bypass O 0
was O 0
used O 0
from O 0
January O 0
2004 O 0
to O 0
December O 0
2010 O 0
. O 0

A O 0
convulsive B-Disease 0
seizure B-Disease 0
was O 0
defined O 0
as O 0
a O 0
transient O 0
episode O 0
of O 0
disturbed O 0
brain O 0
function O 0
characterised O 0
by O 0
abnormal B-Disease 0
involuntary I-Disease 0
motor I-Disease 0
movements I-Disease 0
. O 0

Multivariate O 0
regression O 0
analysis O 0
was O 0
performed O 0
to O 0
identify O 0
independent O 0
predictors O 0
of O 0
postoperative O 0
seizures B-Disease 0
. O 0

A O 0
total O 0
of O 0
100 O 0
( O 0
0 O 0
. O 0
9 O 0
% O 0
) O 0
patients O 0
developed O 0
postoperative O 0
convulsive B-Disease 0
seizures B-Disease 0
. O 0

Generalised B-Disease 0
and I-Disease 0
focal I-Disease 0
seizures I-Disease 0
were O 0
identified O 0
in O 0
68 O 0
and O 0
32 O 0
patients O 0
, O 0
respectively O 0
. O 0

The O 0
median O 0
( O 0
IQR O 0
[ O 0
range O 0
] O 0
) O 0
time O 0
after O 0
surgery O 0
when O 0
the O 0
seizure B-Disease 0
occurred O 0
was O 0
7 O 0
( O 0
6 O 0
- O 0
12 O 0
[ O 0
1 O 0
- O 0
216 O 0
] O 0
) O 0
h O 0
and O 0
8 O 0
( O 0
6 O 0
- O 0
11 O 0
[ O 0
4 O 0
- O 0
18 O 0
] O 0
) O 0
h O 0
, O 0
respectively O 0
. O 0

Epileptiform O 0
findings O 0
on O 0
electroencephalography O 0
were O 0
seen O 0
in O 0
19 O 0
patients O 0
. O 0

Independent O 0
predictors O 0
of O 0
postoperative O 0
seizures B-Disease 0
included O 0
age O 0
, O 0
female O 0
sex O 0
, O 0
redo O 0
cardiac O 0
surgery O 0
, O 0
calcification O 0
of O 0
ascending O 0
aorta O 0
, O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
, O 0
deep O 0
hypothermic B-Disease 0
circulatory O 0
arrest O 0
, O 0
duration O 0
of O 0
aortic O 0
cross O 0
- O 0
clamp O 0
and O 0
tranexamic B-Chemical 0
acid I-Chemical 0
. O 0

When O 0
tested O 0
in O 0
a O 0
multivariate O 0
regression O 0
analysis O 0
, O 0
tranexamic B-Chemical 0
acid I-Chemical 0
was O 0
a O 0
strong O 0
independent O 0
predictor O 0
of O 0
seizures B-Disease 0
( O 0
OR O 0
14 O 0
. O 0
3 O 0
, O 0
95 O 0
% O 0
CI O 0
5 O 0
. O 0
5 O 0
- O 0
36 O 0
. O 0
7 O 0
; O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Patients O 0
with O 0
convulsive B-Disease 0
seizures B-Disease 0
had O 0
2 O 0
. O 0
5 O 0
times O 0
higher O 0
in O 0
- O 0
hospital O 0
mortality O 0
rates O 0
and O 0
twice O 0
the O 0
length O 0
of O 0
hospital O 0
stay O 0
compared O 0
with O 0
patients O 0
without O 0
convulsive B-Disease 0
seizures B-Disease 0
. O 0

Mean O 0
( O 0
IQR O 0
[ O 0
range O 0
] O 0
) O 0
length O 0
of O 0
stay O 0
in O 0
the O 0
intensive O 0
care O 0
unit O 0
was O 0
115 O 0
( O 0
49 O 0
- O 0
228 O 0
[ O 0
32 O 0
- O 0
481 O 0
] O 0
) O 0
h O 0
in O 0
patients O 0
with O 0
convulsive B-Disease 0
seizures B-Disease 0
compared O 0
with O 0
26 O 0
( O 0
22 O 0
- O 0
69 O 0
[ O 0
14 O 0
- O 0
1080 O 0
] O 0
) O 0
h O 0
in O 0
patients O 0
without O 0
seizures B-Disease 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Convulsive B-Disease 0
seizures B-Disease 0
are O 0
a O 0
serious O 0
postoperative B-Disease 0
complication I-Disease 0
after O 0
cardiac O 0
surgery O 0
. O 0

As O 0
tranexamic B-Chemical 0
acid I-Chemical 0
is O 0
the O 0
only O 0
modifiable O 0
factor O 0
, O 0
its O 0
administration O 0
, O 0
particularly O 0
in O 0
doses O 0
exceeding O 0
80 O 0
mg O 0
. O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
, O 0
should O 0
be O 0
weighed O 0
against O 0
the O 0
risk O 0
of O 0
postoperative O 0
seizures B-Disease 0
. O 0

Dysfunctional B-Disease 0
overnight I-Disease 0
memory I-Disease 0
consolidation O 0
in O 0
ecstasy B-Chemical 0
users O 0
. O 0

Sleep O 0
plays O 0
an O 0
important O 0
role O 0
in O 0
the O 0
consolidation O 0
and O 0
integration O 0
of O 0
memory O 0
in O 0
a O 0
process O 0
called O 0
overnight O 0
memory O 0
consolidation O 0
. O 0

Previous O 0
studies O 0
indicate O 0
that O 0
ecstasy B-Chemical 0
users O 0
have O 0
marked O 0
and O 0
persistent O 0
neurocognitive O 0
and O 0
sleep B-Disease 0
- I-Disease 0
related I-Disease 0
impairments I-Disease 0
. O 0

We O 0
extend O 0
past O 0
research O 0
by O 0
examining O 0
overnight O 0
memory O 0
consolidation O 0
among O 0
regular O 0
ecstasy B-Chemical 0
users O 0
( O 0
n O 0
= O 0
12 O 0
) O 0
and O 0
drug O 0
naive O 0
healthy O 0
controls O 0
( O 0
n O 0
= O 0
26 O 0
) O 0
. O 0

Memory O 0
recall O 0
of O 0
word O 0
pairs O 0
was O 0
evaluated O 0
before O 0
and O 0
after O 0
a O 0
period O 0
of O 0
sleep O 0
, O 0
with O 0
and O 0
without O 0
interference O 0
prior O 0
to O 0
testing O 0
. O 0

In O 0
addition O 0
, O 0
we O 0
assessed O 0
neurocognitive O 0
performances O 0
across O 0
tasks O 0
of O 0
learning O 0
, O 0
memory O 0
and O 0
executive O 0
functioning O 0
. O 0

Ecstasy B-Chemical 0
users O 0
demonstrated O 0
impaired B-Disease 0
overnight I-Disease 0
memory I-Disease 0
consolidation O 0
, O 0
a O 0
finding O 0
that O 0
was O 0
more O 0
pronounced O 0
following O 0
associative O 0
interference O 0
. O 0

Additionally O 0
, O 0
ecstasy B-Chemical 0
users O 0
demonstrated O 0
impairments O 0
on O 0
tasks O 0
recruiting O 0
frontostriatal O 0
and O 0
hippocampal O 0
neural O 0
circuitry O 0
, O 0
in O 0
the O 0
domains O 0
of O 0
proactive O 0
interference O 0
memory O 0
, O 0
long O 0
- O 0
term O 0
memory O 0
, O 0
encoding O 0
, O 0
working O 0
memory O 0
and O 0
complex O 0
planning O 0
. O 0

We O 0
suggest O 0
that O 0
ecstasy B-Chemical 0
- O 0
associated O 0
dysfunction O 0
in O 0
fronto O 0
- O 0
temporal O 0
circuitry O 0
may O 0
underlie O 0
overnight O 0
consolidation O 0
memory B-Disease 0
impairments I-Disease 0
in O 0
regular O 0
ecstasy B-Chemical 0
users O 0
. O 0

Normoammonemic O 0
encephalopathy B-Disease 0
: O 0
solely O 0
valproate B-Chemical 0
induced O 0
or O 0
multiple O 0
mechanisms O 0
? O 0

A O 0
77 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
presented O 0
with O 0
subacute O 0
onset O 0
progressive O 0
confusion B-Disease 0
, O 0
aggression B-Disease 0
, O 0
auditory B-Disease 0
hallucinations I-Disease 0
and O 0
delusions B-Disease 0
. O 0

In O 0
the O 0
preceding O 0
months O 0
, O 0
the O 0
patient O 0
had O 0
a O 0
number O 0
of O 0
admissions O 0
with O 0
transient O 0
unilateral O 0
hemiparesis B-Disease 0
with O 0
facial O 0
droop O 0
, O 0
and O 0
had O 0
been O 0
started O 0
on O 0
valproate B-Chemical 0
for O 0
presumed O 0
hemiplegic B-Disease 0
migraine I-Disease 0
. O 0

Valproate B-Chemical 0
was O 0
withdrawn O 0
soon O 0
after O 0
admission O 0
and O 0
her O 0
cognitive O 0
abilities O 0
have O 0
gradually O 0
improved O 0
over O 0
3 O 0
months O 0
of O 0
follow O 0
- O 0
up O 0
. O 0

Valproate B-Chemical 0
levels O 0
taken O 0
prior O 0
to O 0
withdrawal O 0
were O 0
subtherapeutic O 0
and O 0
the O 0
patient O 0
was O 0
normoammonaemic O 0
. O 0

EEG O 0
undertaken O 0
during O 0
inpatient O 0
stay O 0
showed O 0
changes O 0
consistent O 0
with O 0
encephalopathy B-Disease 0
, O 0
and O 0
low O 0
titre O 0
N B-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
- I-Chemical 0
D I-Chemical 0
- I-Chemical 0
aspartate I-Chemical 0
( O 0
NMDA B-Chemical 0
) O 0
receptor O 0
antibodies O 0
were O 0
present O 0
in O 0
this O 0
patient O 0
. O 0

The O 0
possible O 0
aetiologies O 0
of O 0
valproate B-Chemical 0
- O 0
induced O 0
encephalopathy B-Disease 0
and O 0
NMDA B-Chemical 0
receptor O 0
- O 0
associated O 0
encephalitis B-Disease 0
present O 0
a O 0
diagnostic O 0
dilemma O 0
. O 0

We O 0
present O 0
a O 0
putative O 0
combinatorial O 0
hypothesis O 0
to O 0
explain O 0
this O 0
patient O 0
' O 0
s O 0
symptoms O 0
. O 0

Cerebellar B-Disease 0
and I-Disease 0
oculomotor I-Disease 0
dysfunction I-Disease 0
induced O 0
by O 0
rapid O 0
infusion O 0
of O 0
pethidine B-Chemical 0
. O 0

Pethidine B-Chemical 0
is O 0
an O 0
opioid O 0
that O 0
gains O 0
its O 0
popularity O 0
for O 0
the O 0
effective O 0
pain B-Disease 0
control O 0
through O 0
acting O 0
on O 0
the O 0
opioid O 0
- O 0
receptors O 0
. O 0

However O 0
, O 0
rapid O 0
pain B-Disease 0
relief O 0
sometimes O 0
brings O 0
about O 0
unfavourable O 0
side O 0
effects O 0
that O 0
largely O 0
limit O 0
its O 0
clinical O 0
utility O 0
. O 0

Common O 0
side O 0
effects O 0
include O 0
nausea B-Disease 0
, O 0
vomiting B-Disease 0
and O 0
hypotension B-Disease 0
. O 0

In O 0
patients O 0
with O 0
impaired B-Disease 0
renal I-Disease 0
and I-Disease 0
liver I-Disease 0
function I-Disease 0
, O 0
and O 0
those O 0
who O 0
need O 0
long O 0
- O 0
term O 0
pain B-Disease 0
control O 0
, O 0
pethidine B-Chemical 0
may O 0
cause O 0
excitatory O 0
central O 0
nervous O 0
system O 0
( O 0
CNS O 0
) O 0
effects O 0
through O 0
its O 0
neurotoxic B-Disease 0
metabolite O 0
, O 0
norpethidine B-Chemical 0
, O 0
resulting O 0
in O 0
irritability B-Disease 0
and O 0
seizure B-Disease 0
attack O 0
. O 0

On O 0
the O 0
contrary O 0
, O 0
though O 0
not O 0
clinically O 0
apparent O 0
, O 0
pethidine B-Chemical 0
potentially O 0
causes O 0
inhibitory O 0
impacts O 0
on O 0
the O 0
CNS O 0
and O 0
impairs O 0
normal O 0
cerebellar O 0
and O 0
oculomotor O 0
function O 0
in O 0
the O 0
short O 0
term O 0
. O 0

In O 0
this O 0
case O 0
report O 0
, O 0
we O 0
highlight O 0
opioid O 0
' O 0
s O 0
inhibitory O 0
side O 0
effects O 0
on O 0
the O 0
cerebellar O 0
structure O 0
that O 0
causes O 0
dysmetria B-Disease 0
, O 0
dysarthria B-Disease 0
, O 0
reduced O 0
smooth O 0
pursuit O 0
gain O 0
and O 0
decreased O 0
saccadic O 0
velocity O 0
. O 0

Baboon B-Disease 0
syndrome I-Disease 0
induced O 0
by O 0
ketoconazole B-Chemical 0
. O 0

A O 0
27 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
patient O 0
presented O 0
with O 0
a O 0
maculopapular B-Disease 0
eruption I-Disease 0
on O 0
the O 0
flexural O 0
areas O 0
and O 0
buttocks O 0
after O 0
using O 0
oral O 0
ketoconazole B-Chemical 0
. O 0

The O 0
patient O 0
was O 0
diagnosed O 0
with O 0
drug O 0
- O 0
induced O 0
baboon B-Disease 0
syndrome I-Disease 0
based O 0
on O 0
his O 0
history O 0
, O 0
which O 0
included O 0
prior O 0
sensitivity O 0
to O 0
topical O 0
ketoconazole B-Chemical 0
, O 0
a O 0
physical O 0
examination O 0
, O 0
and O 0
histopathological O 0
findings O 0
. O 0

Baboon B-Disease 0
syndrome I-Disease 0
is O 0
a O 0
drug O 0
- O 0
or O 0
contact O 0
allergen O 0
- O 0
related O 0
maculopapular B-Disease 0
eruption I-Disease 0
that O 0
typically O 0
involves O 0
the O 0
flexural O 0
and O 0
gluteal O 0
areas O 0
. O 0

To O 0
the O 0
best O 0
of O 0
our O 0
knowledge O 0
, O 0
this O 0
is O 0
the O 0
first O 0
reported O 0
case O 0
of O 0
ketoconazole B-Chemical 0
- O 0
induced O 0
baboon B-Disease 0
syndrome I-Disease 0
in O 0
the O 0
English O 0
literature O 0
. O 0

A O 0
Case O 0
of O 0
Sudden B-Disease 0
Cardiac I-Disease 0
Death I-Disease 0
due O 0
to O 0
Pilsicainide B-Chemical 0
- O 0
Induced O 0
Torsades B-Disease 0
de I-Disease 0
Pointes I-Disease 0
. O 0

An O 0
84 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
received O 0
oral O 0
pilsicainide B-Chemical 0
, O 0
a O 0
pure O 0
sodium B-Chemical 0
channel O 0
blocker O 0
with O 0
slow O 0
recovery O 0
kinetics O 0
, O 0
to O 0
convert O 0
his O 0
paroxysmal O 0
atrial B-Disease 0
fibrillation I-Disease 0
to O 0
a O 0
sinus O 0
rhythm O 0
; O 0
the O 0
patient O 0
developed O 0
sudden B-Disease 0
cardiac I-Disease 0
death I-Disease 0
two O 0
days O 0
later O 0
. O 0

The O 0
Holter O 0
electrocardiogram O 0
, O 0
which O 0
was O 0
worn O 0
by O 0
chance O 0
, O 0
revealed O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
with O 0
gradually O 0
prolonged O 0
QT O 0
intervals O 0
. O 0

This O 0
drug O 0
is O 0
rapidly O 0
absorbed O 0
from O 0
the O 0
gastrointestinal O 0
tract O 0
, O 0
and O 0
most O 0
of O 0
it O 0
is O 0
excreted O 0
from O 0
the O 0
kidney O 0
. O 0

Although O 0
the O 0
patient O 0
' O 0
s O 0
renal O 0
function O 0
was O 0
not O 0
highly O 0
impaired O 0
and O 0
the O 0
dose O 0
of O 0
pilsicainide B-Chemical 0
was O 0
low O 0
, O 0
the O 0
plasma O 0
concentration O 0
of O 0
pilsicainide B-Chemical 0
may O 0
have O 0
been O 0
high O 0
, O 0
which O 0
can O 0
produce O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
in O 0
the O 0
octogenarian O 0
. O 0

Although O 0
the O 0
oral O 0
administration O 0
of O 0
class O 0
IC O 0
drugs O 0
, O 0
including O 0
pilsicainide B-Chemical 0
, O 0
is O 0
effective O 0
to O 0
terminate O 0
atrial B-Disease 0
fibrillation I-Disease 0
, O 0
careful O 0
consideration O 0
must O 0
be O 0
taken O 0
before O 0
giving O 0
these O 0
drugs O 0
to O 0
octogenarians O 0
. O 0

All B-Chemical 0
- I-Chemical 0
trans I-Chemical 0
retinoic I-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
inflammatory O 0
myositis B-Disease 0
in O 0
a O 0
patient O 0
with O 0
acute B-Disease 0
promyelocytic I-Disease 0
leukemia I-Disease 0
. O 0

All B-Chemical 0
- I-Chemical 0
trans I-Chemical 0
retinoic I-Chemical 0
acid I-Chemical 0
( O 0
ATRA B-Chemical 0
) O 0
, O 0
a O 0
component O 0
of O 0
standard O 0
therapy O 0
for O 0
acute B-Disease 0
promyelocytic I-Disease 0
leukemia I-Disease 0
( O 0
APL B-Disease 0
) O 0
, O 0
is O 0
associated O 0
with O 0
potentially O 0
serious O 0
but O 0
treatable O 0
adverse O 0
effects O 0
involving O 0
numerous O 0
organ O 0
systems O 0
, O 0
including O 0
rare O 0
skeletal O 0
muscle O 0
involvement O 0
. O 0

Only O 0
a O 0
handful O 0
of O 0
cases O 0
of O 0
ATRA B-Chemical 0
- O 0
induced O 0
myositis B-Disease 0
in O 0
children O 0
have O 0
been O 0
reported O 0
, O 0
and O 0
none O 0
in O 0
the O 0
radiology O 0
literature O 0
. O 0

We O 0
present O 0
such O 0
a O 0
case O 0
in O 0
a O 0
15 O 0
- O 0
year O 0
- O 0
old O 0
boy O 0
with O 0
APL B-Disease 0
, O 0
where O 0
recognition O 0
of O 0
imaging O 0
findings O 0
played O 0
a O 0
crucial O 0
role O 0
in O 0
making O 0
the O 0
diagnosis O 0
and O 0
facilitated O 0
prompt O 0
, O 0
effective O 0
treatment O 0
. O 0

Tolerability O 0
of O 0
lomustine B-Chemical 0
in O 0
combination O 0
with O 0
cyclophosphamide B-Chemical 0
in O 0
dogs O 0
with O 0
lymphoma B-Disease 0
. O 0

This O 0
retrospective O 0
study O 0
describes O 0
toxicity B-Disease 0
associated O 0
with O 0
a O 0
protocol O 0
of O 0
lomustine B-Chemical 0
( O 0
CCNU B-Chemical 0
) O 0
and O 0
cyclophosphamide B-Chemical 0
( O 0
CTX B-Chemical 0
) O 0
in O 0
dogs O 0
with O 0
lymphoma B-Disease 0
. O 0

CCNU B-Chemical 0
was O 0
administered O 0
per O 0
os O 0
( O 0
PO O 0
) O 0
at O 0
a O 0
targeted O 0
dosage O 0
of O 0
60 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
body O 0
surface O 0
area O 0
on O 0
day O 0
0 O 0
, O 0
CTX B-Chemical 0
was O 0
administered O 0
PO O 0
at O 0
a O 0
targeted O 0
dosage O 0
of O 0
250 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
divided O 0
over O 0
days O 0
0 O 0
through O 0
4 O 0
, O 0
and O 0
all O 0
dogs O 0
received O 0
prophylactic O 0
antibiotics O 0
. O 0

Ninety O 0
treatments O 0
were O 0
given O 0
to O 0
the O 0
57 O 0
dogs O 0
included O 0
in O 0
the O 0
study O 0
. O 0

Neutropenia B-Disease 0
was O 0
the O 0
principal O 0
toxic O 0
effect O 0
, O 0
and O 0
the O 0
overall O 0
frequency O 0
of O 0
grade O 0
4 O 0
neutropenia B-Disease 0
after O 0
the O 0
first O 0
treatment O 0
of O 0
CCNU B-Chemical 0
/ O 0
CTX B-Chemical 0
was O 0
30 O 0
% O 0
( O 0
95 O 0
% O 0
confidence O 0
interval O 0
, O 0
19 O 0
- O 0
43 O 0
% O 0
) O 0
. O 0

The O 0
mean O 0
body O 0
weight O 0
of O 0
dogs O 0
with O 0
grade O 0
4 O 0
neutropenia B-Disease 0
( O 0
19 O 0
. O 0
7 O 0
kg O 0
+ O 0
13 O 0
. O 0
4 O 0
kg O 0
) O 0
was O 0
significantly O 0
less O 0
than O 0
the O 0
mean O 0
body O 0
weight O 0
of O 0
dogs O 0
that O 0
did O 0
not O 0
develop O 0
grade O 0
4 O 0
neutropenia B-Disease 0
( O 0
31 O 0
. O 0
7 O 0
kg O 0
+ O 0
12 O 0
. O 0
4 O 0
kg O 0
; O 0
P O 0
= O 0
. O 0
005 O 0
) O 0
. O 0

One O 0
dog O 0
( O 0
3 O 0
% O 0
) O 0
developed O 0
hematologic O 0
changes O 0
suggestive O 0
of O 0
hepatotoxicity B-Disease 0
. O 0

No O 0
dogs O 0
had O 0
evidence O 0
of O 0
either O 0
renal B-Disease 0
toxicity I-Disease 0
or O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
. O 0

Adverse O 0
gastrointestinal O 0
effects O 0
were O 0
uncommon O 0
. O 0

On O 0
the O 0
basis O 0
of O 0
the O 0
findings O 0
reported O 0
herein O 0
, O 0
a O 0
dose O 0
of O 0
60 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
of O 0
CCNU B-Chemical 0
combined O 0
with O 0
250 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
of O 0
CTX B-Chemical 0
( O 0
divided O 0
over O 0
5 O 0
days O 0
) O 0
q O 0
4 O 0
wk O 0
is O 0
tolerable O 0
in O 0
tumor B-Disease 0
- O 0
bearing O 0
dogs O 0
. O 0

Nelarabine B-Chemical 0
neurotoxicity B-Disease 0
with O 0
concurrent O 0
intrathecal O 0
chemotherapy O 0
: O 0
Case O 0
report O 0
and O 0
review O 0
of O 0
literature O 0
. O 0

Severe O 0
nelarabine B-Chemical 0
neurotoxicity B-Disease 0
in O 0
a O 0
patient O 0
who O 0
received O 0
concurrent O 0
intrathecal O 0
( O 0
IT O 0
) O 0
chemotherapy O 0
is O 0
reported O 0
. O 0

A O 0
37 O 0
- O 0
year O 0
- O 0
old O 0
Caucasian O 0
woman O 0
with O 0
a O 0
history O 0
of O 0
T B-Disease 0
- I-Disease 0
cell I-Disease 0
lymphoblastic I-Disease 0
lymphoma I-Disease 0
was O 0
admitted O 0
for O 0
relapsed O 0
disease O 0
. O 0

She O 0
was O 0
originally O 0
treated O 0
with O 0
induction O 0
chemotherapy O 0
followed O 0
by O 0
an O 0
autologous O 0
transplant O 0
. O 0

She O 0
developed O 0
relapsed O 0
disease O 0
10 O 0
months O 0
later O 0
with O 0
leukemic B-Disease 0
involvement O 0
. O 0

She O 0
was O 0
re O 0
- O 0
induced O 0
with O 0
nelarabine B-Chemical 0
1500 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
on O 0
days O 0
1 O 0
, O 0
3 O 0
, O 0
and O 0
5 O 0
with O 0
1 O 0
dose O 0
of O 0
IT O 0
cytarabine B-Chemical 0
100 O 0
mg O 0
on O 0
day O 0
2 O 0
as O 0
central O 0
nervous O 0
system O 0
( O 0
CNS O 0
) O 0
prophylaxis O 0
. O 0

At O 0
the O 0
time O 0
of O 0
treatment O 0
, O 0
she O 0
was O 0
on O 0
continuous O 0
renal O 0
replacement O 0
therapy O 0
due O 0
to O 0
sequelae O 0
of O 0
tumor B-Disease 0
lysis I-Disease 0
syndrome I-Disease 0
( O 0
TLS B-Disease 0
) O 0
. O 0

She O 0
tolerated O 0
therapy O 0
well O 0
, O 0
entered O 0
a O 0
complete O 0
remission O 0
, O 0
and O 0
recovered O 0
her O 0
renal O 0
function O 0
. O 0

She O 0
received O 0
a O 0
second O 0
cycle O 0
of O 0
nelarabine B-Chemical 0
without O 0
additional O 0
IT O 0
prophylaxis O 0
one O 0
month O 0
later O 0
. O 0

A O 0
week O 0
after O 0
this O 0
second O 0
cycle O 0
, O 0
she O 0
noted O 0
numbness O 0
in O 0
her O 0
lower O 0
extremities O 0
. O 0

Predominantly O 0
sensory O 0
, O 0
though O 0
also O 0
motor O 0
and O 0
autonomic O 0
, O 0
peripheral B-Disease 0
neuropathy I-Disease 0
started O 0
in O 0
her O 0
feet O 0
, O 0
ascended O 0
proximally O 0
to O 0
the O 0
mid O 0
- O 0
thoracic O 0
region O 0
, O 0
and O 0
eventually O 0
included O 0
her O 0
distal O 0
upper O 0
extremities O 0
. O 0

A O 0
magnetic O 0
resonance O 0
imaging O 0
( O 0
MRI O 0
) O 0
of O 0
her O 0
spine O 0
demonstrated O 0
changes O 0
from O 0
C2 O 0
to O 0
C6 O 0
consistent O 0
with O 0
subacute O 0
combined O 0
degeneration O 0
. O 0

Nelarabine B-Chemical 0
was O 0
felt O 0
to O 0
be O 0
the O 0
cause O 0
of O 0
her O 0
symptoms O 0
. O 0

Her O 0
neuropathy B-Disease 0
stabilized O 0
and O 0
showed O 0
slight O 0
improvement O 0
and O 0
ultimately O 0
received O 0
an O 0
unrelated O 0
, O 0
reduced O 0
- O 0
intensity O 0
allogeneic O 0
transplant O 0
while O 0
in O 0
complete O 0
remission O 0
, O 0
but O 0
relapsed O 0
disease O 0
10 O 0
weeks O 0
later O 0
. O 0

She O 0
is O 0
currently O 0
being O 0
treated O 0
with O 0
best O 0
supportive O 0
care O 0
. O 0

To O 0
our O 0
knowledge O 0
, O 0
this O 0
is O 0
the O 0
first O 0
published O 0
case O 0
report O 0
of O 0
severe O 0
neurotoxicity B-Disease 0
caused O 0
by O 0
nelarabine B-Chemical 0
in O 0
a O 0
patient O 0
who O 0
received O 0
concurrent O 0
IT O 0
chemotherapy O 0
. O 0

Valproate B-Chemical 0
- O 0
induced O 0
hyperammonemic B-Disease 0
encephalopathy B-Disease 0
in O 0
a O 0
renal O 0
transplanted O 0
patient O 0
. O 0

Neurological B-Disease 0
complications I-Disease 0
after O 0
renal O 0
transplantation O 0
constitute O 0
an O 0
important O 0
cause O 0
of O 0
morbidity O 0
and O 0
mortality O 0
. O 0

Their O 0
differential O 0
diagnosis O 0
is O 0
difficult O 0
and O 0
essential O 0
for O 0
subsequent O 0
patient O 0
' O 0
s O 0
management O 0
. O 0

Valproate B-Chemical 0
- O 0
induced O 0
hyperammonemic B-Disease 0
encephalopathy B-Disease 0
is O 0
an O 0
uncommon O 0
but O 0
serious O 0
effect O 0
of O 0
valproate B-Chemical 0
treatment O 0
. O 0

Here O 0
, O 0
we O 0
describe O 0
the O 0
case O 0
of O 0
a O 0
15 O 0
- O 0
year O 0
- O 0
old O 0
girl O 0
who O 0
was O 0
on O 0
a O 0
long O 0
- O 0
term O 0
therapy O 0
with O 0
valproate B-Chemical 0
due O 0
to O 0
epilepsy B-Disease 0
and O 0
revealed O 0
impaired B-Disease 0
consciousness I-Disease 0
with O 0
hyperammonemia B-Disease 0
12 O 0
days O 0
after O 0
renal O 0
transplantation O 0
. O 0

After O 0
withdraw O 0
of O 0
valproate B-Chemical 0
, O 0
patients O 0
' O 0
symptoms O 0
resolved O 0
within O 0
24 O 0
h O 0
. O 0

Clinicians O 0
should O 0
increase O 0
their O 0
awareness O 0
for O 0
potential O 0
complication O 0
of O 0
valproate B-Chemical 0
, O 0
especially O 0
in O 0
transplanted O 0
patients O 0
. O 0

Necrotising B-Disease 0
fasciitis I-Disease 0
after O 0
bortezomib B-Chemical 0
and O 0
dexamethasone B-Chemical 0
- O 0
containing O 0
regimen O 0
in O 0
an O 0
elderly O 0
patient O 0
of O 0
Waldenstrom B-Disease 0
macroglobulinaemia I-Disease 0
. O 0

Bortezomib B-Chemical 0
and O 0
high O 0
- O 0
dose O 0
dexamethasone B-Chemical 0
- O 0
containing O 0
regimens O 0
are O 0
considered O 0
to O 0
be O 0
generally O 0
tolerable O 0
with O 0
few O 0
severe O 0
bacterial B-Disease 0
infections I-Disease 0
in O 0
patients O 0
with O 0
B O 0
- O 0
cell O 0
malignancies B-Disease 0
. O 0

However O 0
, O 0
information O 0
is O 0
limited O 0
concerning O 0
the O 0
safety O 0
of O 0
the O 0
regimen O 0
in O 0
elderly O 0
patients O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
a O 0
76 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
Waldenstrom B-Disease 0
macroglobulinaemia I-Disease 0
who O 0
suffered O 0
necrotising B-Disease 0
fasciitis I-Disease 0
without O 0
neutropenia B-Disease 0
after O 0
the O 0
combination O 0
treatment O 0
with O 0
bortezomib B-Chemical 0
, O 0
high O 0
- O 0
dose O 0
dexamethasone B-Chemical 0
and O 0
rituximab O 0
. O 0

Despite O 0
immediate O 0
intravenous O 0
antimicrobial O 0
therapy O 0
, O 0
he O 0
succumbed O 0
23 O 0
h O 0
after O 0
the O 0
onset O 0
. O 0

Physicians O 0
should O 0
recognise O 0
the O 0
possibility O 0
of O 0
fatal O 0
bacterial B-Disease 0
infections I-Disease 0
related O 0
to O 0
bortezomib B-Chemical 0
plus O 0
high O 0
- O 0
dose O 0
dexamethasone B-Chemical 0
in O 0
elderly O 0
patients O 0
, O 0
and O 0
we O 0
believe O 0
this O 0
case O 0
warrants O 0
further O 0
investigation O 0
. O 0

An O 0
integrated O 0
characterization O 0
of O 0
serological O 0
, O 0
pathological O 0
, O 0
and O 0
functional O 0
events O 0
in O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

Many O 0
efficacious O 0
cancer B-Disease 0
treatments O 0
cause O 0
significant O 0
cardiac O 0
morbidity O 0
, O 0
yet O 0
biomarkers O 0
or O 0
functional O 0
indices O 0
of O 0
early O 0
damage O 0
, O 0
which O 0
would O 0
allow O 0
monitoring O 0
and O 0
intervention O 0
, O 0
are O 0
lacking O 0
. O 0

In O 0
this O 0
study O 0
, O 0
we O 0
have O 0
utilized O 0
a O 0
rat O 0
model O 0
of O 0
progressive O 0
doxorubicin B-Chemical 0
( O 0
DOX B-Chemical 0
) O 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
, O 0
applying O 0
multiple O 0
approaches O 0
, O 0
including O 0
cardiac O 0
magnetic O 0
resonance O 0
imaging O 0
( O 0
MRI O 0
) O 0
, O 0
to O 0
provide O 0
the O 0
most O 0
comprehensive O 0
characterization O 0
to O 0
date O 0
of O 0
the O 0
timecourse O 0
of O 0
serological O 0
, O 0
pathological O 0
, O 0
and O 0
functional O 0
events O 0
underlying O 0
this O 0
toxicity B-Disease 0
. O 0

Hannover O 0
Wistar O 0
rats O 0
were O 0
dosed O 0
with O 0
1 O 0
. O 0
25 O 0
mg O 0
/ O 0
kg O 0
DOX B-Chemical 0
weekly O 0
for O 0
8 O 0
weeks O 0
followed O 0
by O 0
a O 0
4 O 0
week O 0
off O 0
- O 0
dosing O 0
" O 0
recovery O 0
" O 0
period O 0
. O 0

Electron O 0
microscopy O 0
of O 0
the O 0
myocardium O 0
revealed O 0
subcellular B-Disease 0
degeneration I-Disease 0
and O 0
marked O 0
mitochondrial O 0
changes O 0
after O 0
a O 0
single O 0
dose O 0
. O 0

Histopathological O 0
analysis O 0
revealed O 0
progressive O 0
cardiomyocyte B-Disease 0
degeneration I-Disease 0
, O 0
hypertrophy B-Disease 0
/ O 0
cytomegaly O 0
, O 0
and O 0
extensive O 0
vacuolation O 0
after O 0
two O 0
doses O 0
. O 0

Extensive O 0
replacement O 0
fibrosis B-Disease 0
( O 0
quantified O 0
by O 0
Sirius O 0
red O 0
staining O 0
) O 0
developed O 0
during O 0
the O 0
off O 0
- O 0
dosing O 0
period O 0
. O 0

Functional O 0
indices O 0
assessed O 0
by O 0
cardiac O 0
MRI O 0
( O 0
including O 0
left O 0
ventricular O 0
ejection O 0
fraction O 0
( O 0
LVEF O 0
) O 0
, O 0
cardiac O 0
output O 0
, O 0
and O 0
E O 0
/ O 0
A O 0
ratio O 0
) O 0
declined O 0
progressively O 0
, O 0
reaching O 0
statistical O 0
significance O 0
after O 0
two O 0
doses O 0
and O 0
culminating O 0
in O 0
" O 0
clinical O 0
" O 0
LV B-Disease 0
dysfunction I-Disease 0
by O 0
12 O 0
weeks O 0
. O 0

Significant O 0
increases O 0
in O 0
peak O 0
myocardial O 0
contrast O 0
enhancement O 0
and O 0
serological O 0
cardiac O 0
troponin O 0
I O 0
( O 0
cTnI O 0
) O 0
emerged O 0
after O 0
eight O 0
doses O 0
, O 0
importantly O 0
preceding O 0
the O 0
LVEF O 0
decline O 0
to O 0
< O 0
50 O 0
% O 0
. O 0

Troponin O 0
I O 0
levels O 0
positively O 0
correlated O 0
with O 0
delayed O 0
and O 0
peak O 0
gadolinium B-Chemical 0
contrast O 0
enhancement O 0
, O 0
histopathological O 0
grading O 0
, O 0
and O 0
diastolic B-Disease 0
dysfunction I-Disease 0
. O 0

In O 0
summary O 0
, O 0
subcellular O 0
cardiomyocyte B-Disease 0
degeneration I-Disease 0
was O 0
the O 0
earliest O 0
marker O 0
, O 0
followed O 0
by O 0
progressive O 0
functional O 0
decline O 0
and O 0
histopathological O 0
manifestations O 0
. O 0

Myocardial O 0
contrast O 0
enhancement O 0
and O 0
elevations O 0
in O 0
cTnI O 0
occurred O 0
later O 0
. O 0

However O 0
, O 0
all O 0
indices O 0
predated O 0
" O 0
clinical O 0
" O 0
LV B-Disease 0
dysfunction I-Disease 0
and O 0
thus O 0
warrant O 0
further O 0
evaluation O 0
as O 0
predictive O 0
biomarkers O 0
. O 0

Intradermal O 0
glutamate B-Chemical 0
and O 0
capsaicin B-Chemical 0
injections O 0
: O 0
intra O 0
- O 0
and O 0
interindividual O 0
variability O 0
of O 0
provoked O 0
hyperalgesia B-Disease 0
and O 0
allodynia B-Disease 0
. O 0

Intradermal O 0
injections O 0
of O 0
glutamate B-Chemical 0
and O 0
capsaicin B-Chemical 0
are O 0
attractive O 0
to O 0
use O 0
in O 0
human O 0
experimental O 0
pain B-Disease 0
models O 0
because O 0
hyperalgesia B-Disease 0
and O 0
allodynia B-Disease 0
mimic O 0
isolated O 0
aspects O 0
of O 0
clinical O 0
pain B-Disease 0
disorders I-Disease 0
. O 0

The O 0
aim O 0
of O 0
the O 0
present O 0
study O 0
was O 0
to O 0
investigate O 0
the O 0
reproducibility O 0
of O 0
these O 0
models O 0
. O 0

Twenty O 0
healthy O 0
male O 0
volunteers O 0
( O 0
mean O 0
age O 0
24 O 0
years O 0
; O 0
range O 0
18 O 0
- O 0
38 O 0
years O 0
) O 0
received O 0
intradermal O 0
injections O 0
of O 0
glutamate B-Chemical 0
and O 0
capsaicin B-Chemical 0
in O 0
the O 0
volar O 0
forearm O 0
. O 0

Magnitudes O 0
of O 0
secondary O 0
pinprick O 0
hyperalgesia B-Disease 0
and O 0
brush O 0
- O 0
evoked O 0
allodynia B-Disease 0
were O 0
investigated O 0
using O 0
von O 0
Frey O 0
filaments O 0
( O 0
gauges O 0
10 O 0
, O 0
15 O 0
, O 0
60 O 0
and O 0
100 O 0
g O 0
) O 0
and O 0
brush O 0
strokes O 0
. O 0

Areas O 0
of O 0
secondary B-Disease 0
hyperalgesia I-Disease 0
and O 0
allodynia B-Disease 0
were O 0
quantified O 0
immediately O 0
after O 0
injection O 0
and O 0
after O 0
15 O 0
, O 0
30 O 0
and O 0
60 O 0
min O 0
. O 0

Two O 0
identical O 0
experiments O 0
separated O 0
by O 0
at O 0
least O 0
7 O 0
days O 0
were O 0
performed O 0
. O 0

Reproducibility O 0
across O 0
and O 0
within O 0
volunteers O 0
( O 0
inter O 0
- O 0
and O 0
intra O 0
- O 0
individual O 0
variation O 0
, O 0
respectively O 0
) O 0
was O 0
assessed O 0
using O 0
intraclass O 0
correlation O 0
coefficient O 0
( O 0
ICC O 0
) O 0
and O 0
coefficient O 0
of O 0
variation O 0
( O 0
CV O 0
) O 0
. O 0

Secondary O 0
pinprick O 0
hyperalgesia B-Disease 0
was O 0
observed O 0
as O 0
a O 0
marked O 0
increase O 0
in O 0
the O 0
visual O 0
analogue O 0
scale O 0
( O 0
VAS O 0
) O 0
response O 0
to O 0
von O 0
Frey O 0
gauges O 0
60 O 0
and O 0
100 O 0
g O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
after O 0
glutamate B-Chemical 0
injection O 0
. O 0

For O 0
capsaicin B-Chemical 0
, O 0
secondary O 0
pinprick O 0
hyperalgesia B-Disease 0
was O 0
detected O 0
with O 0
all O 0
von O 0
Frey O 0
gauges O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Glutamate B-Chemical 0
evoked O 0
reproducible O 0
VAS O 0
response O 0
to O 0
all O 0
von O 0
Frey O 0
gauges O 0
( O 0
ICC O 0
> O 0
0 O 0
. O 0
60 O 0
) O 0
and O 0
brush O 0
strokes O 0
( O 0
ICC O 0
> O 0
0 O 0
. O 0
83 O 0
) O 0
. O 0

Capsaicin B-Chemical 0
injection O 0
was O 0
reproducible O 0
for O 0
secondary B-Disease 0
hyperalgesia I-Disease 0
( O 0
ICC O 0
> O 0
0 O 0
. O 0
70 O 0
) O 0
and O 0
allodynia B-Disease 0
( O 0
ICC O 0
> O 0
0 O 0
. O 0
71 O 0
) O 0
. O 0

Intra O 0
- O 0
individual O 0
variability O 0
was O 0
generally O 0
lower O 0
for O 0
the O 0
VAS O 0
response O 0
to O 0
von O 0
Frey O 0
and O 0
brush O 0
compared O 0
with O 0
areas O 0
of O 0
secondary B-Disease 0
hyperalgesia I-Disease 0
and O 0
allodynia B-Disease 0
. O 0

In O 0
conclusion O 0
, O 0
glutamate B-Chemical 0
and O 0
capsaicin B-Chemical 0
yield O 0
reproducible O 0
hyperalgesic B-Disease 0
and O 0
allodynic B-Disease 0
responses O 0
, O 0
and O 0
the O 0
present O 0
model O 0
is O 0
well O 0
suited O 0
for O 0
basic O 0
research O 0
, O 0
as O 0
well O 0
as O 0
for O 0
assessing O 0
the O 0
modulation O 0
of O 0
central O 0
phenomena O 0
. O 0

Ocular O 0
- O 0
specific O 0
ER O 0
stress O 0
reduction O 0
rescues O 0
glaucoma B-Disease 0
in O 0
murine O 0
glucocorticoid O 0
- O 0
induced O 0
glaucoma B-Disease 0
. O 0

Administration O 0
of O 0
glucocorticoids O 0
induces O 0
ocular B-Disease 0
hypertension I-Disease 0
in O 0
some O 0
patients O 0
. O 0

If O 0
untreated O 0
, O 0
these O 0
patients O 0
can O 0
develop O 0
a O 0
secondary O 0
glaucoma B-Disease 0
that O 0
resembles O 0
primary B-Disease 0
open I-Disease 0
- I-Disease 0
angle I-Disease 0
glaucoma I-Disease 0
( O 0
POAG B-Disease 0
) O 0
. O 0

The O 0
underlying O 0
pathology O 0
of O 0
glucocorticoid O 0
- O 0
induced O 0
glaucoma B-Disease 0
is O 0
not O 0
fully O 0
understood O 0
, O 0
due O 0
in O 0
part O 0
to O 0
lack O 0
of O 0
an O 0
appropriate O 0
animal O 0
model O 0
. O 0

Here O 0
, O 0
we O 0
developed O 0
a O 0
murine O 0
model O 0
of O 0
glucocorticoid O 0
- O 0
induced O 0
glaucoma B-Disease 0
that O 0
exhibits O 0
glaucoma B-Disease 0
features O 0
that O 0
are O 0
observed O 0
in O 0
patients O 0
. O 0

Treatment O 0
of O 0
WT O 0
mice O 0
with O 0
topical O 0
ocular O 0
0 O 0
. O 0
1 O 0
% O 0
dexamethasone B-Chemical 0
led O 0
to O 0
elevation O 0
of O 0
intraocular O 0
pressure O 0
( O 0
IOP O 0
) O 0
, O 0
functional O 0
and O 0
structural O 0
loss O 0
of O 0
retinal B-Disease 0
ganglion I-Disease 0
cells O 0
, O 0
and O 0
axonal B-Disease 0
degeneration I-Disease 0
, O 0
resembling O 0
glucocorticoid O 0
- O 0
induced O 0
glaucoma B-Disease 0
in O 0
human O 0
patients O 0
. O 0

Furthermore O 0
, O 0
dexamethasone B-Chemical 0
- O 0
induced O 0
ocular B-Disease 0
hypertension I-Disease 0
was O 0
associated O 0
with O 0
chronic O 0
ER O 0
stress O 0
of O 0
the O 0
trabecular O 0
meshwork O 0
( O 0
TM O 0
) O 0
. O 0

Similar O 0
to O 0
patients O 0
, O 0
withdrawal O 0
of O 0
dexamethasone B-Chemical 0
treatment O 0
reduced O 0
elevated O 0
IOP O 0
and O 0
ER O 0
stress O 0
in O 0
this O 0
animal O 0
model O 0
. O 0

Dexamethasone B-Chemical 0
induced O 0
the O 0
transcriptional O 0
factor O 0
CHOP O 0
, O 0
a O 0
marker O 0
for O 0
chronic O 0
ER O 0
stress O 0
, O 0
in O 0
the O 0
anterior O 0
segment O 0
tissues O 0
, O 0
and O 0
Chop O 0
deletion O 0
reduced O 0
ER O 0
stress O 0
in O 0
these O 0
tissues O 0
and O 0
prevented O 0
dexamethasone B-Chemical 0
- O 0
induced O 0
ocular B-Disease 0
hypertension I-Disease 0
. O 0

Furthermore O 0
, O 0
reduction O 0
of O 0
ER O 0
stress O 0
in O 0
the O 0
TM O 0
with O 0
sodium B-Chemical 0
4 I-Chemical 0
- I-Chemical 0
phenylbutyrate I-Chemical 0
prevented O 0
dexamethasone B-Chemical 0
- O 0
induced O 0
ocular B-Disease 0
hypertension I-Disease 0
in O 0
WT O 0
mice O 0
. O 0

Our O 0
data O 0
indicate O 0
that O 0
ER O 0
stress O 0
contributes O 0
to O 0
glucocorticoid O 0
- O 0
induced O 0
ocular B-Disease 0
hypertension I-Disease 0
and O 0
suggest O 0
that O 0
reducing O 0
ER O 0
stress O 0
has O 0
potential O 0
as O 0
a O 0
therapeutic O 0
strategy O 0
for O 0
treating O 0
glucocorticoid O 0
- O 0
induced O 0
glaucoma B-Disease 0
. O 0

Effects O 0
of O 0
ginsenosides B-Chemical 0
on O 0
opioid O 0
- O 0
induced O 0
hyperalgesia B-Disease 0
in O 0
mice O 0
. O 0

Opioid O 0
- O 0
induced O 0
hyperalgesia B-Disease 0
( O 0
OIH B-Disease 0
) O 0
is O 0
characterized O 0
by O 0
nociceptive O 0
sensitization O 0
caused O 0
by O 0
the O 0
cessation O 0
of O 0
chronic O 0
opioid O 0
use O 0
. O 0

OIH B-Disease 0
can O 0
limit O 0
the O 0
clinical O 0
use O 0
of O 0
opioid O 0
analgesics O 0
and O 0
complicate O 0
withdrawal O 0
from O 0
opioid B-Disease 0
addiction I-Disease 0
. O 0

In O 0
this O 0
study O 0
, O 0
we O 0
investigated O 0
the O 0
effects O 0
of O 0
Re B-Chemical 0
, I-Chemical 0
Rg1 I-Chemical 0
, I-Chemical 0
and I-Chemical 0
Rb1 I-Chemical 0
ginsenosides I-Chemical 0
, O 0
the O 0
bioactive O 0
components O 0
of O 0
ginseng O 0
, O 0
on O 0
OIH B-Disease 0
. O 0

OIH B-Disease 0
was O 0
achieved O 0
in O 0
mice O 0
after O 0
subcutaneous O 0
administration O 0
of O 0
morphine B-Chemical 0
for O 0
7 O 0
consecutive O 0
days O 0
three O 0
times O 0
per O 0
day O 0
. O 0

During O 0
withdrawal O 0
( O 0
days O 0
8 O 0
and O 0
9 O 0
) O 0
, O 0
these O 0
mice O 0
were O 0
administered O 0
Re B-Chemical 0
, O 0
Rg1 B-Chemical 0
, O 0
or O 0
Rb1 B-Chemical 0
intragastrically O 0
two O 0
times O 0
per O 0
day O 0
. O 0

On O 0
the O 0
test O 0
day O 0
( O 0
day O 0
10 O 0
) O 0
, O 0
mice O 0
were O 0
subjected O 0
to O 0
the O 0
thermal O 0
sensitivity O 0
test O 0
and O 0
the O 0
acetic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
writhing O 0
test O 0
. O 0

Re B-Chemical 0
( O 0
300 O 0
mg O 0
/ O 0
kg O 0
) O 0
inhibited O 0
OIH B-Disease 0
in O 0
both O 0
the O 0
thermal O 0
sensitivity O 0
test O 0
and O 0
the O 0
acetic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
writhing O 0
test O 0
. O 0

However O 0
, O 0
the O 0
Rg1 B-Chemical 0
and I-Chemical 0
Rb1 I-Chemical 0
ginsenosides I-Chemical 0
failed O 0
to O 0
prevent O 0
OIH B-Disease 0
in O 0
either O 0
test O 0
. O 0

Furthermore O 0
, O 0
Rg1 B-Chemical 0
showed O 0
a O 0
tendency O 0
to O 0
aggravate O 0
OIH B-Disease 0
in O 0
the O 0
acetic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
writhing O 0
test O 0
. O 0

Our O 0
data O 0
suggested O 0
that O 0
the O 0
ginsenoside B-Chemical 0
Re I-Chemical 0
, O 0
but O 0
not O 0
Rg1 B-Chemical 0
or O 0
Rb1 B-Chemical 0
, O 0
may O 0
contribute O 0
toward O 0
reversal O 0
of O 0
OIH B-Disease 0
. O 0

A O 0
comparison O 0
of O 0
severe O 0
hemodynamic O 0
disturbances O 0
between O 0
dexmedetomidine B-Chemical 0
and O 0
propofol B-Chemical 0
for O 0
sedation O 0
in O 0
neurocritical O 0
care O 0
patients O 0
. O 0

OBJECTIVE O 0
: O 0
Dexmedetomidine B-Chemical 0
and O 0
propofol B-Chemical 0
are O 0
commonly O 0
used O 0
sedatives O 0
in O 0
neurocritical O 0
care O 0
as O 0
they O 0
allow O 0
for O 0
frequent O 0
neurologic O 0
examinations O 0
. O 0

However O 0
, O 0
both O 0
agents O 0
are O 0
associated O 0
with O 0
significant O 0
hemodynamic O 0
side O 0
effects O 0
. O 0

The O 0
primary O 0
objective O 0
of O 0
this O 0
study O 0
is O 0
to O 0
compare O 0
the O 0
prevalence O 0
of O 0
severe O 0
hemodynamic O 0
effects O 0
in O 0
neurocritical O 0
care O 0
patients O 0
receiving O 0
dexmedetomidine B-Chemical 0
and O 0
propofol B-Chemical 0
. O 0

DESIGN O 0
: O 0
Multicenter O 0
, O 0
retrospective O 0
, O 0
propensity O 0
- O 0
matched O 0
cohort O 0
study O 0
. O 0

SETTING O 0
: O 0
Neurocritical O 0
care O 0
units O 0
at O 0
two O 0
academic O 0
medical O 0
centers O 0
with O 0
dedicated O 0
neurocritical O 0
care O 0
teams O 0
and O 0
board O 0
- O 0
certified O 0
neurointensivists O 0
. O 0

PATIENTS O 0
: O 0
Neurocritical O 0
care O 0
patients O 0
admitted O 0
between O 0
July O 0
2009 O 0
and O 0
September O 0
2012 O 0
were O 0
evaluated O 0
and O 0
then O 0
matched O 0
1 O 0
: O 0
1 O 0
based O 0
on O 0
propensity O 0
scoring O 0
of O 0
baseline O 0
characteristics O 0
. O 0

INTERVENTIONS O 0
: O 0
Continuous O 0
sedation O 0
with O 0
dexmedetomidine B-Chemical 0
or O 0
propofol B-Chemical 0
. O 0

MEASUREMENTS O 0
AND O 0
MAIN O 0
RESULTS O 0
: O 0
A O 0
total O 0
of O 0
342 O 0
patients O 0
( O 0
105 O 0
dexmedetomidine B-Chemical 0
and O 0
237 O 0
propofol B-Chemical 0
) O 0
were O 0
included O 0
in O 0
the O 0
analysis O 0
, O 0
with O 0
190 O 0
matched O 0
( O 0
95 O 0
in O 0
each O 0
group O 0
) O 0
by O 0
propensity O 0
score O 0
. O 0

The O 0
primary O 0
outcome O 0
of O 0
this O 0
study O 0
was O 0
a O 0
composite O 0
of O 0
severe O 0
hypotension B-Disease 0
( O 0
mean O 0
arterial O 0
pressure O 0
< O 0
60 O 0
mm O 0
Hg O 0
) O 0
and O 0
bradycardia B-Disease 0
( O 0
heart O 0
rate O 0
< O 0
50 O 0
beats O 0
/ O 0
min O 0
) O 0
during O 0
sedative O 0
infusion O 0
. O 0

No O 0
difference O 0
in O 0
the O 0
primary O 0
composite O 0
outcome O 0
in O 0
both O 0
the O 0
unmatched O 0
( O 0
30 O 0
% O 0
vs O 0
30 O 0
% O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
94 O 0
) O 0
or O 0
matched O 0
cohorts O 0
( O 0
28 O 0
% O 0
vs O 0
34 O 0
% O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
35 O 0
) O 0
could O 0
be O 0
found O 0
. O 0

When O 0
analyzed O 0
separately O 0
, O 0
no O 0
differences O 0
could O 0
be O 0
found O 0
in O 0
the O 0
prevalence O 0
of O 0
severe O 0
hypotension B-Disease 0
or O 0
bradycardia B-Disease 0
in O 0
either O 0
the O 0
unmatched O 0
or O 0
matched O 0
cohorts O 0
. O 0

CONCLUSIONS O 0
: O 0
Severe O 0
hypotension B-Disease 0
and O 0
bradycardia B-Disease 0
occur O 0
at O 0
similar O 0
prevalence O 0
in O 0
neurocritical O 0
care O 0
patients O 0
who O 0
receive O 0
dexmedetomidine B-Chemical 0
or O 0
propofol B-Chemical 0
. O 0

Providers O 0
should O 0
similarly O 0
consider O 0
the O 0
likelihood O 0
of O 0
hypotension B-Disease 0
or O 0
bradycardia B-Disease 0
before O 0
starting O 0
either O 0
sedative O 0
. O 0

Hydroxytyrosol B-Chemical 0
ameliorates O 0
oxidative O 0
stress O 0
and O 0
mitochondrial B-Disease 0
dysfunction I-Disease 0
in O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
in O 0
rats O 0
with O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

Oxidative O 0
stress O 0
is O 0
involved O 0
in O 0
several O 0
processes O 0
including O 0
cancer B-Disease 0
, O 0
aging O 0
and O 0
cardiovascular B-Disease 0
disease I-Disease 0
, O 0
and O 0
has O 0
been O 0
shown O 0
to O 0
potentiate O 0
the O 0
therapeutic O 0
effect O 0
of O 0
drugs O 0
such O 0
as O 0
doxorubicin B-Chemical 0
. O 0

Doxorubicin B-Chemical 0
causes O 0
significant O 0
cardiotoxicity B-Disease 0
characterized O 0
by O 0
marked O 0
increases O 0
in O 0
oxidative O 0
stress O 0
and O 0
mitochondrial B-Disease 0
dysfunction I-Disease 0
. O 0

Herein O 0
, O 0
we O 0
investigate O 0
whether O 0
doxorubicin B-Chemical 0
- O 0
associated O 0
chronic O 0
cardiac B-Disease 0
toxicity I-Disease 0
can O 0
be O 0
ameliorated O 0
with O 0
the O 0
antioxidant O 0
hydroxytyrosol B-Chemical 0
in O 0
rats O 0
with O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

Thirty O 0
- O 0
six O 0
rats O 0
bearing O 0
breast B-Disease 0
tumors I-Disease 0
induced O 0
chemically O 0
were O 0
divided O 0
into O 0
4 O 0
groups O 0
: O 0
control O 0
, O 0
hydroxytyrosol B-Chemical 0
( O 0
0 O 0
. O 0
5mg O 0
/ O 0
kg O 0
, O 0
5days O 0
/ O 0
week O 0
) O 0
, O 0
doxorubicin B-Chemical 0
( O 0
1mg O 0
/ O 0
kg O 0
/ O 0
week O 0
) O 0
, O 0
and O 0
doxorubicin B-Chemical 0
plus O 0
hydroxytyrosol B-Chemical 0
. O 0

Cardiac B-Disease 0
disturbances I-Disease 0
at O 0
the O 0
cellular O 0
and O 0
mitochondrial O 0
level O 0
, O 0
mitochondrial O 0
electron O 0
transport O 0
chain O 0
complexes O 0
I O 0
- O 0
IV O 0
and O 0
apoptosis O 0
- O 0
inducing O 0
factor O 0
, O 0
and O 0
oxidative O 0
stress O 0
markers O 0
have O 0
been O 0
analyzed O 0
. O 0

Hydroxytyrosol B-Chemical 0
improved O 0
the O 0
cardiac B-Disease 0
disturbances I-Disease 0
enhanced O 0
by O 0
doxorubicin B-Chemical 0
by O 0
significantly O 0
reducing O 0
the O 0
percentage O 0
of O 0
altered O 0
mitochondria O 0
and O 0
oxidative O 0
damage O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
hydroxytyrosol B-Chemical 0
improve O 0
the O 0
mitochondrial O 0
electron O 0
transport O 0
chain O 0
. O 0

This O 0
study O 0
demonstrates O 0
that O 0
hydroxytyrosol B-Chemical 0
protect O 0
rat O 0
heart B-Disease 0
damage I-Disease 0
provoked O 0
by O 0
doxorubicin B-Chemical 0
decreasing O 0
oxidative O 0
damage O 0
and O 0
mitochondrial O 0
alterations O 0
. O 0

Amiodarone B-Chemical 0
- O 0
induced O 0
myxoedema B-Disease 0
coma I-Disease 0
. O 0

A O 0
62 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
was O 0
found O 0
to O 0
have O 0
bradycardia B-Disease 0
, O 0
hypothermia B-Disease 0
and O 0
respiratory B-Disease 0
failure I-Disease 0
3 O 0
weeks O 0
after O 0
initiation O 0
of O 0
amiodarone B-Chemical 0
therapy O 0
for O 0
atrial B-Disease 0
fibrillation I-Disease 0
. O 0

Thyroid O 0
- O 0
stimulating O 0
hormone O 0
was O 0
found O 0
to O 0
be O 0
168 O 0
uIU O 0
/ O 0
mL O 0
( O 0
nl O 0
. O 0
0 O 0
. O 0
3 O 0
- O 0
5 O 0
uIU O 0
/ O 0
mL O 0
) O 0
and O 0
free O 0
thyroxine B-Chemical 0
( O 0
FT4 O 0
) O 0
was O 0
< O 0
0 O 0
. O 0
2 O 0
ng O 0
/ O 0
dL O 0
( O 0
nl O 0
. O 0
0 O 0
. O 0
8 O 0
- O 0
1 O 0
. O 0
8 O 0
ng O 0
/ O 0
dL O 0
) O 0
. O 0

He O 0
received O 0
intravenous O 0
fluids O 0
, O 0
vasopressor O 0
therapy O 0
and O 0
stress O 0
dose O 0
steroids B-Chemical 0
; O 0
he O 0
was O 0
intubated O 0
and O 0
admitted O 0
to O 0
the O 0
intensive O 0
care O 0
unit O 0
. O 0

He O 0
received O 0
500 O 0
ug O 0
of O 0
intravenous O 0
levothyroxine B-Chemical 0
in O 0
the O 0
first O 0
18 O 0
h O 0
of O 0
therapy O 0
, O 0
and O 0
150 O 0
ug O 0
intravenous O 0
daily O 0
thereafter O 0
. O 0

Haemodynamic O 0
improvement O 0
, O 0
along O 0
with O 0
complete O 0
recovery O 0
of O 0
mental O 0
status O 0
, O 0
occurred O 0
after O 0
48 O 0
h O 0
. O 0

Twelve O 0
hours O 0
after O 0
the O 0
initiation O 0
of O 0
therapy O 0
, O 0
FT4 O 0
was O 0
0 O 0
. O 0
96 O 0
ng O 0
/ O 0
dL O 0
. O 0

The O 0
patient O 0
was O 0
maintained O 0
on O 0
levothyroxine B-Chemical 0
175 O 0
( O 0
g O 0
POorally O 0
daily O 0
. O 0

A O 0
thyroid O 0
ultrasound O 0
showed O 0
diffuse O 0
heterogeneity O 0
. O 0

The O 0
24 O 0
hour O 0
excretion O 0
of O 0
iodine B-Chemical 0
was O 0
3657 O 0
( O 0
mcg O 0
( O 0
25 O 0
- O 0
756 O 0
( O 0
mcg O 0
) O 0
. O 0

The O 0
only O 0
two O 0
cases O 0
of O 0
amiodarone B-Chemical 0
- O 0
induced O 0
myxoedema B-Disease 0
coma I-Disease 0
in O 0
the O 0
literature O 0
report O 0
patient O 0
death O 0
despite O 0
supportive O 0
therapy O 0
and O 0
thyroid O 0
hormone O 0
replacement O 0
. O 0

This O 0
case O 0
represents O 0
the O 0
most O 0
thoroughly O 0
investigated O 0
case O 0
of O 0
amiodarone B-Chemical 0
- O 0
induced O 0
myxoedema B-Disease 0
coma I-Disease 0
with O 0
a O 0
history O 0
significant O 0
for O 0
subclinical O 0
thyroid B-Disease 0
disease I-Disease 0
. O 0

Use O 0
of O 0
argatroban B-Chemical 0
and O 0
catheter O 0
- O 0
directed O 0
thrombolysis B-Disease 0
with O 0
alteplase O 0
in O 0
an O 0
oncology O 0
patient O 0
with O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
with O 0
thrombosis B-Disease 0
. O 0

PURPOSE O 0
: O 0
The O 0
case O 0
of O 0
an O 0
oncology O 0
patient O 0
who O 0
developed O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
with O 0
thrombosis B-Disease 0
( O 0
HITT B-Disease 0
) O 0
and O 0
was O 0
treated O 0
with O 0
argatroban B-Chemical 0
plus O 0
catheter O 0
- O 0
directed O 0
thrombolysis B-Disease 0
( O 0
CDT O 0
) O 0
with O 0
alteplase O 0
is O 0
presented O 0
. O 0

SUMMARY O 0
: O 0
A O 0
63 O 0
- O 0
year O 0
- O 0
old O 0
Caucasian O 0
man O 0
with O 0
renal O 0
amyloidosis B-Disease 0
undergoing O 0
peripheral O 0
blood O 0
stem O 0
cell O 0
collection O 0
for O 0
an O 0
autologous O 0
stem O 0
cell O 0
transplant O 0
developed O 0
extensive O 0
bilateral O 0
upper B-Disease 0
- I-Disease 0
extremity I-Disease 0
deep I-Disease 0
venous I-Disease 0
thrombosis I-Disease 0
( O 0
DVT B-Disease 0
) O 0
and O 0
pulmonary B-Disease 0
embolism I-Disease 0
secondary O 0
to O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
. O 0

A O 0
continuous O 0
i O 0
. O 0
v O 0
. O 0
infusion O 0
of O 0
argatroban B-Chemical 0
was O 0
initiated O 0
, O 0
and O 0
the O 0
patient O 0
was O 0
managed O 0
on O 0
the O 0
general O 0
medical O 0
floor O 0
. O 0

After O 0
one O 0
week O 0
of O 0
therapy O 0
, O 0
he O 0
was O 0
transferred O 0
to O 0
the O 0
intensive O 0
care O 0
unit O 0
with O 0
cardiopulmonary O 0
compromise O 0
related O 0
to O 0
superior B-Disease 0
vena I-Disease 0
cava I-Disease 0
( I-Disease 0
SVC I-Disease 0
) I-Disease 0
syndrome I-Disease 0
. O 0

A O 0
percutaneous O 0
mechanical O 0
thrombectomy O 0
and O 0
CDT O 0
with O 0
alteplase O 0
were O 0
attempted O 0
, O 0
but O 0
the O 0
procedure O 0
was O 0
aborted O 0
due O 0
to O 0
epistaxis B-Disease 0
. O 0

The O 0
epistaxis B-Disease 0
resolved O 0
the O 0
next O 0
day O 0
, O 0
and O 0
the O 0
patient O 0
was O 0
restarted O 0
on O 0
argatroban B-Chemical 0
. O 0

A O 0
second O 0
percutaneous O 0
mechanical O 0
thrombectomy O 0
was O 0
performed O 0
six O 0
days O 0
later O 0
and O 0
resulted O 0
in O 0
partial O 0
revascularization O 0
of O 0
the O 0
SVC O 0
and O 0
central O 0
veins O 0
. O 0

Postthrombectomy O 0
continuous O 0
CDT O 0
with O 0
alteplase O 0
was O 0
commenced O 0
while O 0
argatroban B-Chemical 0
was O 0
withheld O 0
, O 0
and O 0
complete O 0
patency O 0
of O 0
the O 0
SVC O 0
and O 0
central O 0
veins O 0
was O 0
achieved O 0
after O 0
three O 0
days O 0
of O 0
therapy O 0
. O 0

Alteplase O 0
was O 0
discontinued O 0
, O 0
and O 0
the O 0
patient O 0
was O 0
reinitiated O 0
on O 0
argatroban B-Chemical 0
; O 0
ultimately O 0
, O 0
he O 0
was O 0
transitioned O 0
to O 0
warfarin B-Chemical 0
for O 0
long O 0
- O 0
term O 0
anticoagulation O 0
. O 0

Although O 0
the O 0
patient O 0
recovered O 0
, O 0
he O 0
experienced O 0
permanent O 0
vision B-Disease 0
and I-Disease 0
hearing I-Disease 0
loss I-Disease 0
, O 0
as O 0
well O 0
as O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
renal I-Disease 0
disease I-Disease 0
. O 0

CONCLUSION O 0
: O 0
A O 0
63 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
renal O 0
amyloidosis B-Disease 0
and O 0
SVC B-Disease 0
syndrome I-Disease 0
secondary O 0
to O 0
HITT B-Disease 0
was O 0
successfully O 0
treated O 0
with O 0
argatroban B-Chemical 0
and O 0
CDT O 0
with O 0
alteplase O 0
. O 0

Effects O 0
of O 0
dehydroepiandrosterone B-Chemical 0
in O 0
amphetamine B-Chemical 0
- O 0
induced O 0
schizophrenia B-Disease 0
models O 0
in O 0
mice O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
examine O 0
the O 0
effects O 0
of O 0
dehydroepiandrosterone B-Chemical 0
( O 0
DHEA B-Chemical 0
) O 0
on O 0
animal O 0
models O 0
of O 0
schizophrenia B-Disease 0
. O 0

METHODS O 0
: O 0
Seventy O 0
Swiss O 0
albino O 0
female O 0
mice O 0
( O 0
25 O 0
- O 0
35 O 0
g O 0
) O 0
were O 0
divided O 0
into O 0
4 O 0
groups O 0
: O 0
amphetamine B-Chemical 0
- O 0
free O 0
( O 0
control O 0
) O 0
, O 0
amphetamine B-Chemical 0
, O 0
50 O 0
, O 0
and O 0
100 O 0
mg O 0
/ O 0
kg O 0
DHEA B-Chemical 0
. O 0

The O 0
DHEA B-Chemical 0
was O 0
administered O 0
intraperitoneally O 0
( O 0
ip O 0
) O 0
for O 0
5 O 0
days O 0
. O 0

Amphetamine B-Chemical 0
( O 0
3 O 0
mg O 0
/ O 0
kg O 0
ip O 0
) O 0
induced O 0
hyper B-Disease 0
locomotion O 0
, O 0
apomorphine B-Chemical 0
( O 0
1 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
subcutaneously O 0
[ O 0
sc O 0
] O 0
) O 0
induced O 0
climbing O 0
, O 0
and O 0
haloperidol B-Chemical 0
( O 0
1 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
sc O 0
) O 0
induced O 0
catalepsy B-Disease 0
tests O 0
were O 0
used O 0
as O 0
animal O 0
models O 0
of O 0
schizophrenia B-Disease 0
. O 0

The O 0
study O 0
was O 0
conducted O 0
at O 0
the O 0
Animal O 0
Experiment O 0
Laboratories O 0
, O 0
Department O 0
of O 0
Pharmacology O 0
, O 0
Medical O 0
School O 0
, O 0
Eskisehir O 0
Osmangazi O 0
University O 0
, O 0
Eskisehir O 0
, O 0
Turkey O 0
between O 0
March O 0
and O 0
May O 0
2012 O 0
. O 0

Statistical O 0
analysis O 0
was O 0
carried O 0
out O 0
using O 0
Kruskal O 0
- O 0
Wallis O 0
test O 0
for O 0
hyper B-Disease 0
locomotion O 0
, O 0
and O 0
one O 0
- O 0
way O 0
ANOVA O 0
for O 0
climbing O 0
and O 0
catalepsy B-Disease 0
tests O 0
. O 0

RESULTS O 0
: O 0
In O 0
the O 0
amphetamine B-Chemical 0
- O 0
induced O 0
locomotion O 0
test O 0
, O 0
there O 0
were O 0
significant O 0
increases O 0
in O 0
all O 0
movements O 0
compared O 0
with O 0
the O 0
amphetamine B-Chemical 0
- O 0
free O 0
group O 0
. O 0

Both O 0
DHEA B-Chemical 0
50 O 0
mg O 0
/ O 0
kg O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
, O 0
and O 0
100 O 0
mg O 0
/ O 0
kg O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
significantly O 0
decreased O 0
all O 0
movements O 0
compared O 0
with O 0
the O 0
amphetamine B-Chemical 0
- O 0
induced O 0
locomotion O 0
group O 0
. O 0

There O 0
was O 0
a O 0
significant O 0
difference O 0
between O 0
groups O 0
in O 0
the O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
test O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

There O 0
was O 0
no O 0
significant O 0
difference O 0
between O 0
groups O 0
in O 0
terms O 0
of O 0
total O 0
climbing O 0
time O 0
in O 0
the O 0
apomorphine B-Chemical 0
- O 0
induced O 0
climbing O 0
test O 0
( O 0
p O 0
> O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
We O 0
observed O 0
that O 0
DHEA B-Chemical 0
reduced O 0
locomotor O 0
activity O 0
and O 0
increased O 0
catalepsy B-Disease 0
at O 0
both O 0
doses O 0
, O 0
while O 0
it O 0
had O 0
no O 0
effect O 0
on O 0
climbing O 0
behavior O 0
. O 0

We O 0
suggest O 0
that O 0
DHEA B-Chemical 0
displays O 0
typical O 0
neuroleptic O 0
- O 0
like O 0
effects O 0
, O 0
and O 0
may O 0
be O 0
used O 0
in O 0
the O 0
treatment O 0
of O 0
schizophrenia B-Disease 0
. O 0

Availability O 0
of O 0
human O 0
induced O 0
pluripotent O 0
stem O 0
cell O 0
- O 0
derived O 0
cardiomyocytes O 0
in O 0
assessment O 0
of O 0
drug O 0
potential O 0
for O 0
QT B-Disease 0
prolongation I-Disease 0
. O 0

Field O 0
potential O 0
duration O 0
( O 0
FPD O 0
) O 0
in O 0
human O 0
- O 0
induced O 0
pluripotent O 0
stem O 0
cell O 0
- O 0
derived O 0
cardiomyocytes O 0
( O 0
hiPS O 0
- O 0
CMs O 0
) O 0
, O 0
which O 0
can O 0
express O 0
QT O 0
interval O 0
in O 0
an O 0
electrocardiogram O 0
, O 0
is O 0
reported O 0
to O 0
be O 0
a O 0
useful O 0
tool O 0
to O 0
predict O 0
K B-Chemical 0
( O 0
+ O 0
) O 0
channel O 0
and O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
channel O 0
blocker O 0
effects O 0
on O 0
QT O 0
interval O 0
. O 0

However O 0
, O 0
there O 0
is O 0
no O 0
report O 0
showing O 0
that O 0
this O 0
technique O 0
can O 0
be O 0
used O 0
to O 0
predict O 0
multichannel O 0
blocker O 0
potential O 0
for O 0
QT B-Disease 0
prolongation I-Disease 0
. O 0

The O 0
aim O 0
of O 0
this O 0
study O 0
is O 0
to O 0
show O 0
that O 0
FPD O 0
from O 0
MEA O 0
( O 0
Multielectrode O 0
array O 0
) O 0
of O 0
hiPS O 0
- O 0
CMs O 0
can O 0
detect O 0
QT B-Disease 0
prolongation I-Disease 0
induced O 0
by O 0
multichannel O 0
blockers O 0
. O 0

hiPS O 0
- O 0
CMs O 0
were O 0
seeded O 0
onto O 0
MEA O 0
and O 0
FPD O 0
was O 0
measured O 0
for O 0
2min O 0
every O 0
10min O 0
for O 0
30min O 0
after O 0
drug O 0
exposure O 0
for O 0
the O 0
vehicle O 0
and O 0
each O 0
drug O 0
concentration O 0
. O 0

IKr O 0
and O 0
IKs O 0
blockers O 0
concentration O 0
- O 0
dependently O 0
prolonged O 0
corrected O 0
FPD O 0
( O 0
FPDc O 0
) O 0
, O 0
whereas O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
channel O 0
blockers O 0
concentration O 0
- O 0
dependently O 0
shortened O 0
FPDc O 0
. O 0

Also O 0
, O 0
the O 0
multichannel O 0
blockers O 0
Amiodarone B-Chemical 0
, O 0
Paroxetine B-Chemical 0
, O 0
Terfenadine B-Chemical 0
and O 0
Citalopram B-Chemical 0
prolonged O 0
FPDc O 0
in O 0
a O 0
concentration O 0
dependent O 0
manner O 0
. O 0

Finally O 0
, O 0
the O 0
IKr O 0
blockers O 0
, O 0
Terfenadine B-Chemical 0
and O 0
Citalopram B-Chemical 0
, O 0
which O 0
are O 0
reported O 0
to O 0
cause O 0
Torsade B-Disease 0
de I-Disease 0
Pointes I-Disease 0
( O 0
TdP B-Disease 0
) O 0
in O 0
clinical O 0
practice O 0
, O 0
produced O 0
early O 0
afterdepolarization O 0
( O 0
EAD O 0
) O 0
. O 0

hiPS O 0
- O 0
CMs O 0
using O 0
MEA O 0
system O 0
and O 0
FPDc O 0
can O 0
predict O 0
the O 0
effects O 0
of O 0
drug O 0
candidates O 0
on O 0
QT O 0
interval O 0
. O 0

This O 0
study O 0
also O 0
shows O 0
that O 0
this O 0
assay O 0
can O 0
help O 0
detect O 0
EAD O 0
for O 0
drugs O 0
with O 0
TdP B-Disease 0
potential O 0
. O 0

Dermal O 0
developmental O 0
toxicity B-Disease 0
of O 0
N O 0
- O 0
phenylimide O 0
herbicides O 0
in O 0
rats O 0
. O 0

BACKGROUND O 0
: O 0
S B-Chemical 0
- I-Chemical 0
53482 I-Chemical 0
and O 0
S B-Chemical 0
- I-Chemical 0
23121 I-Chemical 0
are O 0
N O 0
- O 0
phenylimide O 0
herbicides O 0
and O 0
produced O 0
embryolethality B-Disease 0
, O 0
teratogenicity B-Disease 0
( O 0
mainly O 0
ventricular B-Disease 0
septal I-Disease 0
defects I-Disease 0
and O 0
wavy O 0
ribs O 0
) O 0
, O 0
and O 0
growth B-Disease 0
retardation I-Disease 0
in O 0
rats O 0
in O 0
conventional O 0
oral O 0
developmental O 0
toxicity B-Disease 0
studies O 0
. O 0

Our O 0
objective O 0
in O 0
this O 0
study O 0
was O 0
to O 0
investigate O 0
whether O 0
the O 0
compounds O 0
induce O 0
developmental O 0
toxicity B-Disease 0
via O 0
the O 0
dermal O 0
route O 0
, O 0
which O 0
is O 0
more O 0
relevant O 0
to O 0
occupational O 0
exposure O 0
, O 0
hence O 0
better O 0
addressing O 0
human O 0
health O 0
risks O 0
. O 0

METHODS O 0
: O 0
S B-Chemical 0
- I-Chemical 0
53482 I-Chemical 0
was O 0
administered O 0
dermally O 0
to O 0
rats O 0
at O 0
30 O 0
, O 0
100 O 0
, O 0
and O 0
300 O 0
mg O 0
/ O 0
kg O 0
during O 0
organogenesis O 0
, O 0
and O 0
S B-Chemical 0
- I-Chemical 0
23121 I-Chemical 0
was O 0
administered O 0
at O 0
200 O 0
, O 0
400 O 0
, O 0
and O 0
800 O 0
mg O 0
/ O 0
kg O 0
( O 0
the O 0
maximum O 0
applicable O 0
dose O 0
level O 0
) O 0
. O 0

Fetuses O 0
were O 0
obtained O 0
by O 0
a O 0
Cesarean O 0
section O 0
and O 0
examined O 0
for O 0
external O 0
, O 0
visceral O 0
, O 0
and O 0
skeletal O 0
alterations O 0
. O 0

RESULTS O 0
: O 0
Dermal O 0
exposure O 0
of O 0
rats O 0
to O 0
S B-Chemical 0
- I-Chemical 0
53482 I-Chemical 0
at O 0
300 O 0
mg O 0
/ O 0
kg O 0
produced O 0
patterns O 0
of O 0
developmental O 0
toxicity B-Disease 0
similar O 0
to O 0
those O 0
resulting O 0
from O 0
oral O 0
exposure O 0
. O 0

Toxicity B-Disease 0
included O 0
embryolethality B-Disease 0
, O 0
teratogenicity B-Disease 0
, O 0
and O 0
growth B-Disease 0
retardation I-Disease 0
. O 0

Dermal O 0
administration O 0
of O 0
S B-Chemical 0
- I-Chemical 0
23121 I-Chemical 0
at O 0
800 O 0
mg O 0
/ O 0
kg O 0
resulted O 0
in O 0
an O 0
increased O 0
incidence O 0
of O 0
embryonic B-Disease 0
death I-Disease 0
and O 0
ventricular B-Disease 0
septal I-Disease 0
defect I-Disease 0
, O 0
but O 0
retarded O 0
fetal O 0
growth O 0
was O 0
not O 0
observed O 0
as O 0
it O 0
was O 0
following O 0
oral O 0
exposure O 0
to O 0
S B-Chemical 0
- I-Chemical 0
23121 I-Chemical 0
. O 0

CONCLUSIONS O 0
: O 0
Based O 0
on O 0
the O 0
results O 0
, O 0
S B-Chemical 0
- I-Chemical 0
53482 I-Chemical 0
and O 0
S B-Chemical 0
- I-Chemical 0
23121 I-Chemical 0
were O 0
teratogenic B-Disease 0
when O 0
administered O 0
dermally O 0
to O 0
pregnant O 0
rats O 0
as O 0
were O 0
the O 0
compounds O 0
administered O 0
orally O 0
. O 0

Thus O 0
, O 0
investigation O 0
of O 0
the O 0
mechanism O 0
and O 0
its O 0
human O 0
relevancy O 0
become O 0
more O 0
important O 0
. O 0

Rates O 0
of O 0
Renal B-Disease 0
Toxicity I-Disease 0
in O 0
Cancer B-Disease 0
Patients O 0
Receiving O 0
Cisplatin B-Chemical 0
With O 0
and O 0
Without O 0
Mannitol B-Chemical 0
. O 0

BACKGROUND O 0
: O 0
Cisplatin B-Chemical 0
is O 0
a O 0
widely O 0
used O 0
antineoplastic O 0
. O 0

One O 0
of O 0
the O 0
major O 0
complications O 0
of O 0
cisplatin B-Chemical 0
use O 0
is O 0
dose O 0
- O 0
limiting O 0
nephrotoxicity B-Disease 0
. O 0

There O 0
are O 0
many O 0
strategies O 0
to O 0
prevent O 0
this O 0
toxicity B-Disease 0
, O 0
including O 0
the O 0
use O 0
of O 0
mannitol B-Chemical 0
as O 0
a O 0
nephroprotectant O 0
in O 0
combination O 0
with O 0
hydration O 0
. O 0

OBJECTIVE O 0
: O 0
We O 0
aimed O 0
to O 0
evaluate O 0
the O 0
rates O 0
of O 0
cisplatin B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
in O 0
cancer B-Disease 0
patients O 0
receiving O 0
single O 0
- O 0
agent O 0
cisplatin B-Chemical 0
with O 0
and O 0
without O 0
mannitol B-Chemical 0
. O 0

METHODS O 0
: O 0
This O 0
single O 0
- O 0
center O 0
retrospective O 0
analysis O 0
was O 0
a O 0
quasi O 0
experiment O 0
created O 0
by O 0
the O 0
national O 0
mannitol B-Chemical 0
shortage O 0
. O 0

Data O 0
were O 0
collected O 0
on O 0
adult O 0
cancer B-Disease 0
patients O 0
receiving O 0
single O 0
- O 0
agent O 0
cisplatin B-Chemical 0
as O 0
an O 0
outpatient O 0
from O 0
January O 0
2011 O 0
to O 0
September O 0
2012 O 0
. O 0

The O 0
primary O 0
outcome O 0
was O 0
acute B-Disease 0
kidney I-Disease 0
injury I-Disease 0
( O 0
AKI B-Disease 0
) O 0
. O 0

RESULTS O 0
: O 0
We O 0
evaluated O 0
143 O 0
patients O 0
who O 0
received O 0
single O 0
- O 0
agent O 0
cisplatin B-Chemical 0
; O 0
97 O 0
. O 0
2 O 0
% O 0
of O 0
patients O 0
had O 0
head B-Disease 0
and I-Disease 0
neck I-Disease 0
cancer I-Disease 0
as O 0
their O 0
primary O 0
malignancy B-Disease 0
. O 0

Patients O 0
who O 0
did O 0
not O 0
receive O 0
mannitol B-Chemical 0
were O 0
more O 0
likely O 0
to O 0
develop O 0
nephrotoxicity B-Disease 0
: O 0
odds O 0
ratio O 0
[ O 0
OR O 0
] O 0
= O 0
2 O 0
. O 0
646 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
1 O 0
. O 0
008 O 0
, O 0
6 O 0
. O 0
944 O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
048 O 0
) O 0
. O 0

Patients O 0
who O 0
received O 0
the O 0
100 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
dosing O 0
and O 0
patients O 0
who O 0
had O 0
a O 0
history O 0
of O 0
hypertension B-Disease 0
also O 0
had O 0
a O 0
higher O 0
likelihood O 0
of O 0
developing O 0
nephrotoxicity B-Disease 0
: O 0
OR O 0
= O 0
11 O 0
. O 0
494 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
4 O 0
. O 0
149 O 0
, O 0
32 O 0
. O 0
258 O 0
; O 0
P O 0
< O 0
0 O 0
. O 0
0001 O 0
) O 0
and O 0
OR O 0
= O 0
3 O 0
. O 0
219 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
1 O 0
. O 0
228 O 0
, O 0
8 O 0
. O 0
439 O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
017 O 0
) O 0
, O 0
respectively O 0
. O 0

CONCLUSIONS O 0
: O 0
When O 0
limited O 0
quantities O 0
of O 0
mannitol B-Chemical 0
are O 0
available O 0
, O 0
it O 0
should O 0
preferentially O 0
be O 0
given O 0
to O 0
patients O 0
at O 0
particularly O 0
high O 0
risk O 0
of O 0
nephrotoxicity B-Disease 0
. O 0

Our O 0
analysis O 0
suggests O 0
that O 0
those O 0
patients O 0
receiving O 0
the O 0
dosing O 0
schedule O 0
of O 0
100 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
cisplatin B-Chemical 0
every O 0
3 O 0
weeks O 0
and O 0
those O 0
with O 0
hypertension B-Disease 0
are O 0
at O 0
the O 0
greatest O 0
risk O 0
of O 0
nephrotoxicity B-Disease 0
and O 0
would O 0
benefit O 0
from O 0
the O 0
addition O 0
of O 0
mannitol B-Chemical 0
. O 0

Metformin B-Chemical 0
protects O 0
against O 0
seizures B-Disease 0
, O 0
learning B-Disease 0
and I-Disease 0
memory I-Disease 0
impairments I-Disease 0
and O 0
oxidative O 0
damage O 0
induced O 0
by O 0
pentylenetetrazole B-Chemical 0
- O 0
induced O 0
kindling O 0
in O 0
mice O 0
. O 0

Cognitive B-Disease 0
impairment I-Disease 0
, O 0
the O 0
most O 0
common O 0
and O 0
severe O 0
comorbidity O 0
of O 0
epilepsy B-Disease 0
, O 0
greatly O 0
diminishes O 0
the O 0
quality O 0
of O 0
life O 0
. O 0

However O 0
, O 0
current O 0
therapeutic O 0
interventions O 0
for O 0
epilepsy B-Disease 0
can O 0
also O 0
cause O 0
untoward O 0
cognitive O 0
effects O 0
. O 0

Thus O 0
, O 0
there O 0
is O 0
an O 0
urgent O 0
need O 0
for O 0
new O 0
kinds O 0
of O 0
agents O 0
targeting O 0
both O 0
seizures B-Disease 0
and O 0
cognition B-Disease 0
deficits I-Disease 0
. O 0

Oxidative O 0
stress O 0
is O 0
considered O 0
to O 0
play O 0
an O 0
important O 0
role O 0
in O 0
epileptogenesis O 0
and O 0
cognitive B-Disease 0
deficits I-Disease 0
, O 0
and O 0
antioxidants O 0
have O 0
a O 0
putative O 0
antiepileptic O 0
potential O 0
. O 0

Metformin B-Chemical 0
, O 0
the O 0
most O 0
commonly O 0
prescribed O 0
antidiabetic O 0
oral O 0
drug O 0
, O 0
has O 0
antioxidant O 0
properties O 0
. O 0

This O 0
study O 0
was O 0
designed O 0
to O 0
evaluate O 0
the O 0
ameliorative O 0
effects O 0
of O 0
metformin B-Chemical 0
on O 0
seizures B-Disease 0
, O 0
cognitive B-Disease 0
impairment I-Disease 0
and O 0
brain O 0
oxidative O 0
stress O 0
markers O 0
observed O 0
in O 0
pentylenetetrazole B-Chemical 0
- O 0
induced O 0
kindling O 0
animals O 0
. O 0

Male O 0
C57BL O 0
/ O 0
6 O 0
mice O 0
were O 0
administered O 0
with O 0
subconvulsive O 0
dose O 0
of O 0
pentylenetetrazole B-Chemical 0
( O 0
37 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
every O 0
other O 0
day O 0
for O 0
14 O 0
injections O 0
. O 0

Metformin B-Chemical 0
was O 0
injected O 0
intraperitoneally O 0
in O 0
dose O 0
of O 0
200mg O 0
/ O 0
kg O 0
along O 0
with O 0
alternate O 0
- O 0
day O 0
PTZ B-Chemical 0
. O 0

We O 0
found O 0
that O 0
metformin B-Chemical 0
suppressed O 0
the O 0
progression O 0
of O 0
kindling O 0
, O 0
ameliorated O 0
the O 0
cognitive B-Disease 0
impairment I-Disease 0
and O 0
decreased O 0
brain O 0
oxidative O 0
stress O 0
. O 0

Thus O 0
the O 0
present O 0
study O 0
concluded O 0
that O 0
metformin B-Chemical 0
may O 0
be O 0
a O 0
potential O 0
agent O 0
for O 0
the O 0
treatment O 0
of O 0
epilepsy B-Disease 0
as O 0
well O 0
as O 0
a O 0
protective O 0
medicine O 0
against O 0
cognitive B-Disease 0
impairment I-Disease 0
induced O 0
by O 0
seizures B-Disease 0
. O 0

P53 O 0
inhibition O 0
exacerbates O 0
late O 0
- O 0
stage O 0
anthracycline B-Chemical 0
cardiotoxicity B-Disease 0
. O 0

AIMS O 0
: O 0
Doxorubicin B-Chemical 0
( O 0
DOX B-Chemical 0
) O 0
is O 0
an O 0
effective O 0
anti O 0
- O 0
cancer B-Disease 0
therapeutic O 0
, O 0
but O 0
is O 0
associated O 0
with O 0
both O 0
acute O 0
and O 0
late O 0
- O 0
stage O 0
cardiotoxicity B-Disease 0
. O 0

Children O 0
are O 0
particularly O 0
sensitive O 0
to O 0
DOX B-Chemical 0
- O 0
induced O 0
heart B-Disease 0
failure I-Disease 0
. O 0

Here O 0
, O 0
the O 0
impact O 0
of O 0
p53 O 0
inhibition O 0
on O 0
acute O 0
vs O 0
. O 0
late O 0
- O 0
stage O 0
DOX B-Chemical 0
cardiotoxicity B-Disease 0
was O 0
examined O 0
in O 0
a O 0
juvenile O 0
model O 0
. O 0

METHODS O 0
AND O 0
RESULTS O 0
: O 0
Two O 0
- O 0
week O 0
- O 0
old O 0
MHC O 0
- O 0
CB7 O 0
mice O 0
( O 0
which O 0
express O 0
dominant O 0
- O 0
interfering O 0
p53 O 0
in O 0
cardiomyocytes O 0
) O 0
and O 0
their O 0
non O 0
- O 0
transgenic O 0
( O 0
NON O 0
- O 0
TXG O 0
) O 0
littermates O 0
received O 0
weekly O 0
DOX B-Chemical 0
injections O 0
for O 0
5 O 0
weeks O 0
( O 0
25 O 0
mg O 0
/ O 0
kg O 0
cumulative O 0
dose O 0
) O 0
. O 0

One O 0
week O 0
after O 0
the O 0
last O 0
DOX B-Chemical 0
treatment O 0
( O 0
acute O 0
stage O 0
) O 0
, O 0
MHC O 0
- O 0
CB7 O 0
mice O 0
exhibited O 0
improved O 0
cardiac O 0
function O 0
and O 0
lower O 0
levels O 0
of O 0
cardiomyocyte O 0
apoptosis O 0
when O 0
compared O 0
with O 0
the O 0
NON O 0
- O 0
TXG O 0
mice O 0
. O 0

Surprisingly O 0
, O 0
by O 0
13 O 0
weeks O 0
following O 0
the O 0
last O 0
DOX B-Chemical 0
treatment O 0
( O 0
late O 0
stage O 0
) O 0
, O 0
MHC O 0
- O 0
CB7 O 0
exhibited O 0
a O 0
progressive O 0
decrease O 0
in O 0
cardiac O 0
function O 0
and O 0
higher O 0
rates O 0
of O 0
cardiomyocyte O 0
apoptosis O 0
when O 0
compared O 0
with O 0
NON O 0
- O 0
TXG O 0
mice O 0
. O 0

p53 O 0
inhibition O 0
blocked O 0
transient O 0
DOX B-Chemical 0
- O 0
induced O 0
STAT3 O 0
activation O 0
in O 0
MHC O 0
- O 0
CB7 O 0
mice O 0
, O 0
which O 0
was O 0
associated O 0
with O 0
enhanced O 0
induction O 0
of O 0
the O 0
DNA O 0
repair O 0
proteins O 0
Ku70 O 0
and O 0
Ku80 O 0
. O 0

Mice O 0
with O 0
cardiomyocyte O 0
- O 0
restricted O 0
deletion O 0
of O 0
STAT3 O 0
exhibited O 0
worse O 0
cardiac O 0
function O 0
, O 0
higher O 0
levels O 0
of O 0
cardiomyocyte O 0
apoptosis O 0
, O 0
and O 0
a O 0
greater O 0
induction O 0
of O 0
Ku70 O 0
and O 0
Ku80 O 0
in O 0
response O 0
to O 0
DOX B-Chemical 0
treatment O 0
during O 0
the O 0
acute O 0
stage O 0
when O 0
compared O 0
with O 0
control O 0
animals O 0
. O 0

CONCLUSION O 0
: O 0
These O 0
data O 0
support O 0
a O 0
model O 0
wherein O 0
a O 0
p53 O 0
- O 0
dependent O 0
cardioprotective O 0
pathway O 0
, O 0
mediated O 0
via O 0
STAT3 O 0
activation O 0
, O 0
mitigates O 0
DOX B-Chemical 0
- O 0
induced O 0
myocardial O 0
stress O 0
during O 0
drug O 0
delivery O 0
. O 0

Furthermore O 0
, O 0
these O 0
data O 0
suggest O 0
an O 0
explanation O 0
as O 0
to O 0
how O 0
p53 O 0
inhibition O 0
can O 0
result O 0
in O 0
cardioprotection O 0
during O 0
drug O 0
treatment O 0
and O 0
, O 0
paradoxically O 0
, O 0
enhanced O 0
cardiotoxicity B-Disease 0
long O 0
after O 0
the O 0
cessation O 0
of O 0
drug O 0
treatment O 0
. O 0

Metronidazole B-Chemical 0
- O 0
induced O 0
encephalopathy B-Disease 0
: O 0
an O 0
uncommon O 0
scenario O 0
. O 0

Metronidazole B-Chemical 0
can O 0
produce O 0
neurological O 0
complications O 0
although O 0
it O 0
is O 0
not O 0
a O 0
common O 0
scenario O 0
. O 0

We O 0
present O 0
a O 0
case O 0
where O 0
a O 0
patient O 0
developed O 0
features O 0
of O 0
encephalopathy B-Disease 0
following O 0
prolonged O 0
metronidazole B-Chemical 0
intake O 0
. O 0

Magnetic O 0
resonance O 0
imaging O 0
( O 0
MRI O 0
) O 0
brain O 0
showed O 0
abnormal O 0
signal O 0
intensity O 0
involving O 0
both O 0
dentate O 0
nuclei O 0
of O 0
cerebellum O 0
and O 0
splenium O 0
of O 0
corpus O 0
callosum O 0
. O 0

The O 0
diagnosis O 0
of O 0
metronidazole B-Chemical 0
toxicity B-Disease 0
was O 0
made O 0
by O 0
the O 0
MRI O 0
findings O 0
and O 0
supported O 0
clinically O 0
. O 0

Aconitine B-Chemical 0
- O 0
induced O 0
Ca2 B-Chemical 0
+ O 0
overload O 0
causes O 0
arrhythmia B-Disease 0
and O 0
triggers O 0
apoptosis O 0
through O 0
p38 O 0
MAPK O 0
signaling O 0
pathway O 0
in O 0
rats O 0
. O 0

Aconitine B-Chemical 0
is O 0
a O 0
major O 0
bioactive O 0
diterpenoid O 0
alkaloid O 0
with O 0
high O 0
content O 0
derived O 0
from O 0
herbal O 0
aconitum O 0
plants O 0
. O 0

Emerging O 0
evidence O 0
indicates O 0
that O 0
voltage O 0
- O 0
dependent O 0
Na B-Chemical 0
( O 0
+ O 0
) O 0
channels O 0
have O 0
pivotal O 0
roles O 0
in O 0
the O 0
cardiotoxicity B-Disease 0
of O 0
aconitine B-Chemical 0
. O 0

However O 0
, O 0
no O 0
reports O 0
are O 0
available O 0
on O 0
the O 0
role O 0
of O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
in O 0
aconitine B-Chemical 0
poisoning B-Disease 0
. O 0

In O 0
this O 0
study O 0
, O 0
we O 0
explored O 0
the O 0
importance O 0
of O 0
pathological O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
signaling O 0
in O 0
aconitine B-Chemical 0
poisoning B-Disease 0
in O 0
vitro O 0
and O 0
in O 0
vivo O 0
. O 0

We O 0
found O 0
that O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
overload O 0
lead O 0
to O 0
accelerated O 0
beating O 0
rhythm O 0
in O 0
adult O 0
rat O 0
ventricular O 0
myocytes O 0
and O 0
caused O 0
arrhythmia B-Disease 0
in O 0
conscious O 0
freely O 0
moving O 0
rats O 0
. O 0

To O 0
investigate O 0
effects O 0
of O 0
aconitine B-Chemical 0
on O 0
myocardial B-Disease 0
injury I-Disease 0
, O 0
we O 0
performed O 0
cytotoxicity B-Disease 0
assay O 0
in O 0
neonatal O 0
rat O 0
ventricular O 0
myocytes O 0
( O 0
NRVMs O 0
) O 0
, O 0
as O 0
well O 0
as O 0
measured O 0
lactate B-Chemical 0
dehydrogenase O 0
level O 0
in O 0
the O 0
culture O 0
medium O 0
of O 0
NRVMs O 0
and O 0
activities O 0
of O 0
serum O 0
cardiac O 0
enzymes O 0
in O 0
rats O 0
. O 0

The O 0
results O 0
showed O 0
that O 0
aconitine B-Chemical 0
resulted O 0
in O 0
myocardial B-Disease 0
injury I-Disease 0
and O 0
reduced O 0
NRVMs O 0
viability O 0
dose O 0
- O 0
dependently O 0
. O 0

To O 0
confirm O 0
the O 0
pro O 0
- O 0
apoptotic O 0
effects O 0
, O 0
we O 0
performed O 0
flow O 0
cytometric O 0
detection O 0
, O 0
cardiac O 0
histology O 0
, O 0
transmission O 0
electron O 0
microscopy O 0
and O 0
terminal O 0
deoxynucleotidyl O 0
transferase O 0
- O 0
mediated O 0
dUTP B-Chemical 0
- O 0
biotin B-Chemical 0
nick O 0
end O 0
labeling O 0
assay O 0
. O 0

The O 0
results O 0
showed O 0
that O 0
aconitine B-Chemical 0
stimulated O 0
apoptosis O 0
time O 0
- O 0
dependently O 0
. O 0

The O 0
expression O 0
analysis O 0
of O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
handling O 0
proteins O 0
demonstrated O 0
that O 0
aconitine B-Chemical 0
promoted O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
overload O 0
through O 0
the O 0
expression O 0
regulation O 0
of O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
handling O 0
proteins O 0
. O 0

The O 0
expression O 0
analysis O 0
of O 0
apoptosis O 0
- O 0
related O 0
proteins O 0
revealed O 0
that O 0
pro O 0
- O 0
apoptotic O 0
protein O 0
expression O 0
was O 0
upregulated O 0
, O 0
and O 0
anti O 0
- O 0
apoptotic O 0
protein O 0
BCL O 0
- O 0
2 O 0
expression O 0
was O 0
downregulated O 0
. O 0

Furthermore O 0
, O 0
increased O 0
phosphorylation O 0
of O 0
MAPK O 0
family O 0
members O 0
, O 0
especially O 0
the O 0
P O 0
- O 0
P38 O 0
/ O 0
P38 O 0
ratio O 0
was O 0
found O 0
in O 0
cardiac O 0
tissues O 0
. O 0

Hence O 0
, O 0
our O 0
results O 0
suggest O 0
that O 0
aconitine B-Chemical 0
significantly O 0
aggravates O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
overload O 0
and O 0
causes O 0
arrhythmia B-Disease 0
and O 0
finally O 0
promotes O 0
apoptotic O 0
development O 0
via O 0
phosphorylation O 0
of O 0
P38 O 0
mitogen O 0
- O 0
activated O 0
protein O 0
kinase O 0
. O 0

Chronic O 0
treatment O 0
with O 0
metformin B-Chemical 0
suppresses O 0
toll O 0
- O 0
like O 0
receptor O 0
4 O 0
signaling O 0
and O 0
attenuates O 0
left B-Disease 0
ventricular I-Disease 0
dysfunction I-Disease 0
following O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

Acute O 0
treatment O 0
with O 0
metformin B-Chemical 0
has O 0
a O 0
protective O 0
effect O 0
in O 0
myocardial B-Disease 0
infarction I-Disease 0
by O 0
suppression O 0
of O 0
inflammatory O 0
responses O 0
due O 0
to O 0
activation O 0
of O 0
AMP B-Chemical 0
- O 0
activated O 0
protein O 0
kinase O 0
( O 0
AMPK O 0
) O 0
. O 0

In O 0
the O 0
present O 0
study O 0
, O 0
the O 0
effect O 0
of O 0
chronic O 0
pre O 0
- O 0
treatment O 0
with O 0
metformin B-Chemical 0
on O 0
cardiac B-Disease 0
dysfunction I-Disease 0
and O 0
toll O 0
- O 0
like O 0
receptor O 0
4 O 0
( O 0
TLR4 O 0
) O 0
activities O 0
following O 0
myocardial B-Disease 0
infarction I-Disease 0
and O 0
their O 0
relation O 0
with O 0
AMPK O 0
were O 0
assessed O 0
. O 0

Male O 0
Wistar O 0
rats O 0
were O 0
randomly O 0
assigned O 0
to O 0
one O 0
of O 0
5 O 0
groups O 0
( O 0
n O 0
= O 0
6 O 0
) O 0
: O 0
normal O 0
control O 0
and O 0
groups O 0
were O 0
injected O 0
isoproterenol B-Chemical 0
after O 0
chronic O 0
pre O 0
- O 0
treatment O 0
with O 0
0 O 0
, O 0
25 O 0
, O 0
50 O 0
, O 0
or O 0
100mg O 0
/ O 0
kg O 0
of O 0
metformin B-Chemical 0
twice O 0
daily O 0
for O 0
14 O 0
days O 0
. O 0

Isoproterenol B-Chemical 0
( O 0
100mg O 0
/ O 0
kg O 0
) O 0
was O 0
injected O 0
subcutaneously O 0
on O 0
the O 0
13th O 0
and O 0
14th O 0
days O 0
to O 0
induce O 0
acute B-Disease 0
myocardial I-Disease 0
infarction I-Disease 0
. O 0

Isoproterenol B-Chemical 0
alone O 0
decreased O 0
left O 0
ventricular O 0
systolic O 0
pressure O 0
and O 0
myocardial O 0
contractility O 0
indexed O 0
as O 0
LVdp O 0
/ O 0
dtmax O 0
and O 0
LVdp O 0
/ O 0
dtmin O 0
. O 0

The O 0
left B-Disease 0
ventricular I-Disease 0
dysfunction I-Disease 0
was O 0
significantly O 0
lower O 0
in O 0
the O 0
groups O 0
treated O 0
with O 0
25 O 0
and O 0
50mg O 0
/ O 0
kg O 0
of O 0
metformin B-Chemical 0
. O 0

Metfromin O 0
markedly O 0
lowered O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
elevation O 0
in O 0
the O 0
levels O 0
of O 0
TLR4 O 0
mRNA O 0
, O 0
myeloid O 0
differentiation O 0
protein O 0
88 O 0
( O 0
MyD88 O 0
) O 0
, O 0
tumor B-Disease 0
necrosis B-Disease 0
factor O 0
- O 0
alpha O 0
( O 0
TNF O 0
- O 0
a O 0
) O 0
, O 0
and O 0
interleukin O 0
6 O 0
( O 0
IL O 0
- O 0
6 O 0
) O 0
in O 0
the O 0
heart O 0
tissues O 0
. O 0

Similar O 0
changes O 0
were O 0
also O 0
seen O 0
in O 0
the O 0
serum O 0
levels O 0
of O 0
TNF O 0
- O 0
a O 0
and O 0
IL O 0
- O 0
6 O 0
. O 0

However O 0
, O 0
the O 0
lower O 0
doses O 0
of O 0
25 O 0
and O 0
50mg O 0
/ O 0
kg O 0
were O 0
more O 0
effective O 0
than O 0
100mg O 0
/ O 0
kg O 0
. O 0

Phosphorylated O 0
AMPKa O 0
( O 0
p O 0
- O 0
AMPK O 0
) O 0
in O 0
the O 0
myocardium O 0
was O 0
significantly O 0
elevated O 0
by O 0
25mg O 0
/ O 0
kg O 0
of O 0
metformin B-Chemical 0
, O 0
slightly O 0
by O 0
50mg O 0
/ O 0
kg O 0
, O 0
but O 0
not O 0
by O 0
100mg O 0
/ O 0
kg O 0
. O 0

Chronic O 0
pre O 0
- O 0
treatment O 0
with O 0
metformin B-Chemical 0
reduces O 0
post O 0
- O 0
myocardial B-Disease 0
infarction I-Disease 0
cardiac O 0
dysfunction O 0
and O 0
suppresses O 0
inflammatory O 0
responses O 0
, O 0
possibly O 0
through O 0
inhibition O 0
of O 0
TLR4 O 0
activities O 0
. O 0

This O 0
mechanism O 0
can O 0
be O 0
considered O 0
as O 0
a O 0
target O 0
to O 0
protect O 0
infarcted O 0
myocardium O 0
. O 0

Unusual O 0
complications O 0
of O 0
antithyroid O 0
drug O 0
therapy O 0
: O 0
four O 0
case O 0
reports O 0
and O 0
review O 0
of O 0
literature O 0
. O 0

Two O 0
cases O 0
of O 0
propylthiouracil B-Chemical 0
- O 0
associated O 0
acute O 0
hepatitis B-Disease 0
, O 0
one O 0
case O 0
of O 0
fatal O 0
methimazole B-Chemical 0
- O 0
associated O 0
hepatocellular B-Disease 0
necrosis I-Disease 0
and O 0
one O 0
case O 0
of O 0
propylthiouracil B-Chemical 0
- O 0
associated O 0
lupus B-Disease 0
- I-Disease 0
like I-Disease 0
syndrome I-Disease 0
are O 0
described O 0
. O 0

The O 0
literature O 0
related O 0
to O 0
antithyroid O 0
drug O 0
side O 0
effects O 0
and O 0
the O 0
mechanisms O 0
for O 0
their O 0
occurrence O 0
are O 0
reviewed O 0
and O 0
the O 0
efficacy O 0
and O 0
complications O 0
of O 0
thyroidectomy O 0
and O 0
radioiodine O 0
compared O 0
to O 0
those O 0
of O 0
antithyroid O 0
drugs O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
in O 0
most O 0
circumstances O 0
131I O 0
is O 0
the O 0
therapy O 0
of O 0
choice O 0
for O 0
hyperthyroidism B-Disease 0
. O 0

Neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
induced O 0
by O 0
combination O 0
therapy O 0
with O 0
tetrabenazine B-Chemical 0
and O 0
tiapride B-Chemical 0
in O 0
a O 0
Japanese O 0
patient O 0
with O 0
Huntington B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
at O 0
the O 0
terminal O 0
stage O 0
of O 0
recurrent O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

We O 0
herein O 0
describe O 0
the O 0
case O 0
of O 0
an O 0
81 O 0
- O 0
year O 0
- O 0
old O 0
Japanese O 0
woman O 0
with O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
that O 0
occurred O 0
36 O 0
days O 0
after O 0
the O 0
initiation O 0
of O 0
combination O 0
therapy O 0
with O 0
tiapride B-Chemical 0
( O 0
75 O 0
mg O 0
/ O 0
day O 0
) O 0
and O 0
tetrabenazine B-Chemical 0
( O 0
12 O 0
. O 0
5 O 0
mg O 0
/ O 0
day O 0
) O 0
for O 0
Huntington B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

The O 0
patient O 0
had O 0
been O 0
treated O 0
with O 0
tiapride B-Chemical 0
or O 0
tetrabenazine B-Chemical 0
alone O 0
without O 0
any O 0
adverse O 0
effects O 0
before O 0
the O 0
administration O 0
of O 0
the O 0
combination O 0
therapy O 0
. O 0

She O 0
also O 0
had O 0
advanced O 0
breast B-Disease 0
cancer I-Disease 0
when O 0
the O 0
combination O 0
therapy O 0
was O 0
initiated O 0
. O 0

To O 0
the O 0
best O 0
of O 0
our O 0
knowledge O 0
, O 0
the O 0
occurrence O 0
of O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
due O 0
to O 0
combination O 0
therapy O 0
with O 0
tetrabenazine B-Chemical 0
and O 0
tiapride B-Chemical 0
has O 0
not O 0
been O 0
previously O 0
reported O 0
. O 0

Tetrabenazine B-Chemical 0
should O 0
be O 0
administered O 0
very O 0
carefully O 0
in O 0
combination O 0
with O 0
other O 0
neuroleptic B-Chemical 0
drugs I-Chemical 0
, O 0
particularly O 0
in O 0
patients O 0
with O 0
a O 0
worsening O 0
general O 0
condition O 0
. O 0

A O 0
metoprolol B-Chemical 0
- O 0
terbinafine B-Chemical 0
combination O 0
induced O 0
bradycardia B-Disease 0
. O 0

To O 0
report O 0
a O 0
sinus B-Disease 0
bradycardia I-Disease 0
induced O 0
by O 0
metoprolol B-Chemical 0
and O 0
terbinafine B-Chemical 0
drug O 0
- O 0
drug O 0
interaction O 0
and O 0
its O 0
management O 0
. O 0

A O 0
63 O 0
year O 0
- O 0
old O 0
Caucasian O 0
man O 0
on O 0
metoprolol B-Chemical 0
200 O 0
mg O 0
/ O 0
day O 0
for O 0
stable O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
was O 0
prescribed O 0
a O 0
90 O 0
- O 0
day O 0
course O 0
of O 0
oral O 0
terbinafine B-Chemical 0
250 O 0
mg O 0
/ O 0
day O 0
for O 0
onychomycosis B-Disease 0
. O 0

On O 0
the O 0
49th O 0
day O 0
of O 0
terbinafine B-Chemical 0
therapy O 0
, O 0
he O 0
was O 0
brought O 0
to O 0
the O 0
emergency O 0
room O 0
for O 0
a O 0
decrease O 0
of O 0
his O 0
global O 0
health O 0
status O 0
, O 0
confusion B-Disease 0
and O 0
falls O 0
. O 0

The O 0
electrocardiogram O 0
revealed O 0
a O 0
37 O 0
beats O 0
/ O 0
min O 0
sinus B-Disease 0
bradycardia I-Disease 0
. O 0

A O 0
score O 0
of O 0
7 O 0
on O 0
the O 0
Naranjo O 0
adverse B-Disease 0
drug I-Disease 0
reaction I-Disease 0
probability O 0
scale O 0
indicates O 0
a O 0
probable O 0
relationship O 0
between O 0
the O 0
patient O 0
' O 0
s O 0
sinus B-Disease 0
bradycardia I-Disease 0
and O 0
the O 0
drug O 0
interaction O 0
between O 0
metoprolol B-Chemical 0
and O 0
terbinafine B-Chemical 0
. O 0

The O 0
heart O 0
rate O 0
ameliorated O 0
first O 0
with O 0
a O 0
decrease O 0
in O 0
the O 0
dose O 0
of O 0
metoprolol B-Chemical 0
. O 0

It O 0
was O 0
subsequently O 0
changed O 0
to O 0
bisoprolol B-Chemical 0
and O 0
the O 0
heart O 0
rate O 0
remained O 0
normal O 0
. O 0

By O 0
inhibiting O 0
the O 0
cytochrome O 0
P450 O 0
2D6 O 0
, O 0
terbinafine B-Chemical 0
had O 0
decreased O 0
metoprolol B-Chemical 0
' O 0
s O 0
clearance O 0
, O 0
leading O 0
in O 0
metoprolol B-Chemical 0
accumulation O 0
which O 0
has O 0
resulted O 0
in O 0
clinically O 0
significant O 0
sinus B-Disease 0
bradycardia I-Disease 0
. O 0

Optochiasmatic O 0
and O 0
peripheral B-Disease 0
neuropathy I-Disease 0
due O 0
to O 0
ethambutol B-Chemical 0
overtreatment O 0
. O 0

Ethambutol B-Chemical 0
is O 0
known O 0
to O 0
cause O 0
optic B-Disease 0
neuropathy I-Disease 0
and O 0
, O 0
more O 0
rarely O 0
, O 0
axonal O 0
polyneuropathy B-Disease 0
. O 0

We O 0
characterize O 0
the O 0
clinical O 0
, O 0
neurophysiological O 0
, O 0
and O 0
neuroimaging O 0
findings O 0
in O 0
a O 0
72 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
who O 0
developed O 0
visual B-Disease 0
loss I-Disease 0
and O 0
paresthesias B-Disease 0
after O 0
11 O 0
weeks O 0
of O 0
exposure O 0
to O 0
a O 0
supratherapeutic O 0
dose O 0
of O 0
ethambutol B-Chemical 0
. O 0

This O 0
case O 0
demonstrates O 0
the O 0
selective O 0
vulnerability O 0
of O 0
the O 0
anterior O 0
visual O 0
pathways O 0
and O 0
peripheral O 0
nerves O 0
to O 0
ethambutol B-Chemical 0
toxicity B-Disease 0
. O 0

Testosterone B-Chemical 0
ameliorates O 0
streptozotocin B-Chemical 0
- O 0
induced O 0
memory B-Disease 0
impairment I-Disease 0
in O 0
male O 0
rats O 0
. O 0

AIM O 0
: O 0
To O 0
study O 0
the O 0
effects O 0
of O 0
testosterone B-Chemical 0
on O 0
streptozotocin B-Chemical 0
( O 0
STZ B-Chemical 0
) O 0
- O 0
induced O 0
memory B-Disease 0
impairment I-Disease 0
in O 0
male O 0
rats O 0
. O 0

METHODS O 0
: O 0
Adult O 0
male O 0
Wistar O 0
rats O 0
were O 0
intracerebroventricularly O 0
( O 0
icv O 0
) O 0
infused O 0
with O 0
STZ B-Chemical 0
( O 0
750 O 0
ug O 0
) O 0
on O 0
d O 0
1 O 0
and O 0
d O 0
3 O 0
, O 0
and O 0
a O 0
passive O 0
avoidance O 0
task O 0
was O 0
assessed O 0
2 O 0
weeks O 0
after O 0
the O 0
first O 0
injection O 0
of O 0
STZ B-Chemical 0
. O 0

Castration O 0
surgery O 0
was O 0
performed O 0
in O 0
another O 0
group O 0
of O 0
rats O 0
, O 0
and O 0
the O 0
passive O 0
avoidance O 0
task O 0
was O 0
assessed O 0
4 O 0
weeks O 0
after O 0
the O 0
operation O 0
. O 0

Testosterone B-Chemical 0
( O 0
1 O 0
mg O 0
. O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
. O 0
d O 0
( O 0
- O 0
1 O 0
) O 0
, O 0
sc O 0
) O 0
, O 0
the O 0
androgen B-Chemical 0
receptor O 0
antagonist O 0
flutamide B-Chemical 0
( O 0
10 O 0
mg O 0
. O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
. O 0
d O 0
( O 0
- O 0
1 O 0
) O 0
, O 0
ip O 0
) O 0
, O 0
the O 0
estrogen B-Chemical 0
receptor O 0
antagonist O 0
tamoxifen B-Chemical 0
( O 0
1 O 0
mg O 0
. O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
. O 0
d O 0
( O 0
- O 0
1 O 0
) O 0
, O 0
ip O 0
) O 0
or O 0
the O 0
aromatase O 0
inhibitor O 0
letrozole B-Chemical 0
( O 0
4 O 0
mg O 0
. O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
. O 0
d O 0
( O 0
- O 0
1 O 0
) O 0
, O 0
ip O 0
) O 0
were O 0
administered O 0
for O 0
6 O 0
d O 0
after O 0
the O 0
first O 0
injection O 0
of O 0
STZ B-Chemical 0
. O 0

RESULTS O 0
: O 0
STZ B-Chemical 0
administration O 0
and O 0
castration O 0
markedly O 0
decreased O 0
both O 0
STL1 O 0
( O 0
the O 0
short O 0
memory O 0
) O 0
and O 0
STL2 O 0
( O 0
the O 0
long O 0
memory O 0
) O 0
in O 0
passive O 0
avoidance O 0
tests O 0
. O 0

Testosterone B-Chemical 0
replacement O 0
almost O 0
restored O 0
the O 0
STL1 O 0
and O 0
STL2 O 0
in O 0
castrated O 0
rats O 0
, O 0
and O 0
significantly O 0
prolonged O 0
the O 0
STL1 O 0
and O 0
STL2 O 0
in O 0
STZ B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

Administration O 0
of O 0
flutamide B-Chemical 0
, O 0
letrozole B-Chemical 0
or O 0
tamoxifen B-Chemical 0
significantly O 0
impaired B-Disease 0
the I-Disease 0
memory I-Disease 0
in O 0
intact O 0
rats O 0
, O 0
and O 0
significantly O 0
attenuated O 0
the O 0
testosterone B-Chemical 0
replacement O 0
in O 0
improving O 0
STZ B-Chemical 0
- O 0
and O 0
castration O 0
- O 0
induced O 0
memory B-Disease 0
impairment I-Disease 0
. O 0

CONCLUSION O 0
: O 0
Testosterone B-Chemical 0
administration O 0
ameliorates O 0
STZ B-Chemical 0
- O 0
and O 0
castration O 0
- O 0
induced O 0
memory B-Disease 0
impairment I-Disease 0
in O 0
male O 0
Wistar O 0
rats O 0
. O 0

Behavioral O 0
and O 0
neurochemical O 0
studies O 0
in O 0
mice O 0
pretreated O 0
with O 0
garcinielliptone B-Chemical 0
FC I-Chemical 0
in O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
. O 0

Garcinielliptone B-Chemical 0
FC I-Chemical 0
( O 0
GFC B-Chemical 0
) O 0
isolated O 0
from O 0
hexanic O 0
fraction O 0
seed O 0
extract O 0
of O 0
species O 0
Platonia O 0
insignis O 0
Mart O 0
. O 0

It O 0
is O 0
widely O 0
used O 0
in O 0
folk O 0
medicine O 0
to O 0
treat O 0
skin B-Disease 0
diseases I-Disease 0
in O 0
both O 0
humans O 0
and O 0
animals O 0
as O 0
well O 0
as O 0
the O 0
seed O 0
decoction O 0
has O 0
been O 0
used O 0
to O 0
treat O 0
diarrheas B-Disease 0
and O 0
inflammatory B-Disease 0
diseases I-Disease 0
. O 0

However O 0
, O 0
there O 0
is O 0
no O 0
research O 0
on O 0
GFC B-Chemical 0
effects O 0
in O 0
the O 0
central O 0
nervous O 0
system O 0
of O 0
rodents O 0
. O 0

The O 0
present O 0
study O 0
aimed O 0
to O 0
evaluate O 0
the O 0
GFC B-Chemical 0
effects O 0
at O 0
doses O 0
of O 0
25 O 0
, O 0
50 O 0
or O 0
75 O 0
mg O 0
/ O 0
kg O 0
on O 0
seizure B-Disease 0
parameters O 0
to O 0
determine O 0
their O 0
anticonvulsant O 0
activity O 0
and O 0
its O 0
effects O 0
on O 0
amino B-Chemical 0
acid I-Chemical 0
( O 0
r B-Chemical 0
- I-Chemical 0
aminobutyric I-Chemical 0
acid I-Chemical 0
( O 0
GABA B-Chemical 0
) O 0
, O 0
glutamine B-Chemical 0
, O 0
aspartate B-Chemical 0
and O 0
glutathione B-Chemical 0
) O 0
levels O 0
as O 0
well O 0
as O 0
on O 0
acetylcholinesterase O 0
( O 0
AChE O 0
) O 0
activity O 0
in O 0
mice O 0
hippocampus O 0
after O 0
seizures B-Disease 0
. O 0

GFC B-Chemical 0
produced O 0
an O 0
increased O 0
latency O 0
to O 0
first O 0
seizure B-Disease 0
, O 0
at O 0
doses O 0
25mg O 0
/ O 0
kg O 0
( O 0
20 O 0
. O 0
12 O 0
+ O 0
2 O 0
. O 0
20 O 0
min O 0
) O 0
, O 0
50mg O 0
/ O 0
kg O 0
( O 0
20 O 0
. O 0
95 O 0
+ O 0
2 O 0
. O 0
21 O 0
min O 0
) O 0
or O 0
75 O 0
mg O 0
/ O 0
kg O 0
( O 0
23 O 0
. O 0
43 O 0
+ O 0
1 O 0
. O 0
99 O 0
min O 0
) O 0
when O 0
compared O 0
with O 0
seized O 0
mice O 0
. O 0

In O 0
addition O 0
, O 0
GABA B-Chemical 0
content O 0
of O 0
mice O 0
hippocampus O 0
treated O 0
with O 0
GFC75 O 0
plus O 0
P400 O 0
showed O 0
an O 0
increase O 0
of O 0
46 O 0
. O 0
90 O 0
% O 0
when O 0
compared O 0
with O 0
seized O 0
mice O 0
. O 0

In O 0
aspartate B-Chemical 0
, O 0
glutamine B-Chemical 0
and O 0
glutamate B-Chemical 0
levels O 0
detected O 0
a O 0
decrease O 0
of O 0
5 O 0
. O 0
21 O 0
% O 0
, O 0
13 O 0
. O 0
55 O 0
% O 0
and O 0
21 O 0
. O 0
80 O 0
% O 0
, O 0
respectively O 0
in O 0
mice O 0
hippocampus O 0
treated O 0
with O 0
GFC75 O 0
plus O 0
P400 O 0
when O 0
compared O 0
with O 0
seized O 0
mice O 0
. O 0

Hippocampus O 0
mice O 0
treated O 0
with O 0
GFC75 O 0
plus O 0
P400 O 0
showed O 0
an O 0
increase O 0
in O 0
AChE O 0
activity O 0
( O 0
63 O 0
. O 0
30 O 0
% O 0
) O 0
when O 0
compared O 0
with O 0
seized O 0
mice O 0
. O 0

The O 0
results O 0
indicate O 0
that O 0
GFC B-Chemical 0
can O 0
exert O 0
anticonvulsant O 0
activity O 0
and O 0
reduce O 0
the O 0
frequency O 0
of O 0
installation O 0
of O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
status B-Disease 0
epilepticus I-Disease 0
, O 0
as O 0
demonstrated O 0
by O 0
increase O 0
in O 0
latency O 0
to O 0
first O 0
seizure B-Disease 0
and O 0
decrease O 0
in O 0
mortality O 0
rate O 0
of O 0
animals O 0
. O 0

In O 0
conclusion O 0
, O 0
our O 0
data O 0
suggest O 0
that O 0
GFC B-Chemical 0
may O 0
influence O 0
in O 0
epileptogenesis O 0
and O 0
promote O 0
anticonvulsant O 0
actions O 0
in O 0
pilocarpine B-Chemical 0
model O 0
by O 0
modulating O 0
the O 0
GABA B-Chemical 0
and O 0
glutamate B-Chemical 0
contents O 0
and O 0
of O 0
AChE O 0
activity O 0
in O 0
seized O 0
mice O 0
hippocampus O 0
. O 0

This O 0
compound O 0
may O 0
be O 0
useful O 0
to O 0
produce O 0
neuronal O 0
protection O 0
and O 0
it O 0
can O 0
be O 0
considered O 0
as O 0
an O 0
anticonvulsant O 0
agent O 0
. O 0

Standard O 0
operating O 0
procedures O 0
for O 0
antibiotic O 0
therapy O 0
and O 0
the O 0
occurrence O 0
of O 0
acute B-Disease 0
kidney I-Disease 0
injury I-Disease 0
: O 0
a O 0
prospective O 0
, O 0
clinical O 0
, O 0
non O 0
- O 0
interventional O 0
, O 0
observational O 0
study O 0
. O 0

INTRODUCTION O 0
: O 0
Acute B-Disease 0
kidney I-Disease 0
injury I-Disease 0
( O 0
AKI B-Disease 0
) O 0
occurs O 0
in O 0
7 O 0
% O 0
of O 0
hospitalized O 0
and O 0
66 O 0
% O 0
of O 0
Intensive O 0
Care O 0
Unit O 0
( O 0
ICU O 0
) O 0
patients O 0
. O 0

It O 0
increases O 0
mortality O 0
, O 0
hospital O 0
length O 0
of O 0
stay O 0
, O 0
and O 0
costs O 0
. O 0

The O 0
aim O 0
of O 0
this O 0
study O 0
was O 0
to O 0
investigate O 0
, O 0
whether O 0
there O 0
is O 0
an O 0
association O 0
between O 0
adherence O 0
to O 0
guidelines O 0
( O 0
standard O 0
operating O 0
procedures O 0
( O 0
SOP O 0
) O 0
) O 0
for O 0
potentially O 0
nephrotoxic B-Disease 0
antibiotics O 0
and O 0
the O 0
occurrence O 0
of O 0
AKI B-Disease 0
. O 0

METHODS O 0
: O 0
This O 0
study O 0
was O 0
carried O 0
out O 0
as O 0
a O 0
prospective O 0
, O 0
clinical O 0
, O 0
non O 0
- O 0
interventional O 0
, O 0
observational O 0
study O 0
. O 0

Data O 0
collection O 0
was O 0
performed O 0
over O 0
a O 0
total O 0
of O 0
170 O 0
days O 0
in O 0
three O 0
ICUs O 0
at O 0
Charite O 0
- O 0
Universitaetsmedizin O 0
Berlin O 0
. O 0

A O 0
total O 0
of O 0
675 O 0
patients O 0
were O 0
included O 0
; O 0
163 O 0
of O 0
these O 0
had O 0
therapy O 0
with O 0
vancomycin B-Chemical 0
, O 0
gentamicin B-Chemical 0
, O 0
or O 0
tobramycin B-Chemical 0
; O 0
were O 0
> O 0
18 O 0
years O 0
; O 0
and O 0
treated O 0
in O 0
the O 0
ICU O 0
for O 0
> O 0
24 O 0
hours O 0
. O 0

Patients O 0
with O 0
an O 0
adherence O 0
to O 0
SOP O 0
> O 0
70 O 0
% O 0
were O 0
classified O 0
into O 0
the O 0
high O 0
adherence O 0
group O 0
( O 0
HAG O 0
) O 0
and O 0
patients O 0
with O 0
an O 0
adherence O 0
of O 0
< O 0
70 O 0
% O 0
into O 0
the O 0
low O 0
adherence O 0
group O 0
( O 0
LAG O 0
) O 0
. O 0

AKI B-Disease 0
was O 0
defined O 0
according O 0
to O 0
RIFLE O 0
criteria O 0
. O 0

Adherence O 0
to O 0
SOPs O 0
was O 0
evaluated O 0
by O 0
retrospective O 0
expert O 0
audit O 0
. O 0

Development O 0
of O 0
AKI B-Disease 0
was O 0
compared O 0
between O 0
groups O 0
with O 0
exact O 0
Chi2 O 0
- O 0
test O 0
and O 0
multivariate O 0
logistic O 0
regression O 0
analysis O 0
( O 0
two O 0
- O 0
sided O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

RESULTS O 0
: O 0
LAG O 0
consisted O 0
of O 0
75 O 0
patients O 0
( O 0
46 O 0
% O 0
) O 0
versus O 0
88 O 0
HAG O 0
patients O 0
( O 0
54 O 0
% O 0
) O 0
. O 0

AKI B-Disease 0
occurred O 0
significantly O 0
more O 0
often O 0
in O 0
LAG O 0
with O 0
36 O 0
% O 0
versus O 0
21 O 0
% O 0
in O 0
HAG O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
035 O 0
) O 0
. O 0

Basic O 0
characteristics O 0
were O 0
comparable O 0
, O 0
except O 0
an O 0
increased O 0
rate O 0
of O 0
soft O 0
tissue O 0
infections B-Disease 0
in O 0
LAG O 0
. O 0

Multivariate O 0
analysis O 0
revealed O 0
an O 0
odds O 0
ratio O 0
of O 0
2 O 0
. O 0
5 O 0
- O 0
fold O 0
for O 0
LAG O 0
to O 0
develop O 0
AKI B-Disease 0
compared O 0
with O 0
HAG O 0
( O 0
95 O 0
% O 0
confidence O 0
interval O 0
1 O 0
. O 0
195 O 0
to O 0
5 O 0
. O 0
124 O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
039 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
Low O 0
adherence O 0
to O 0
SOPs O 0
for O 0
potentially O 0
nephrotoxic B-Disease 0
antibiotics O 0
was O 0
associated O 0
with O 0
a O 0
higher O 0
occurrence O 0
of O 0
AKI B-Disease 0
. O 0

TRIAL O 0
REGISTRATION O 0
: O 0
Current O 0
Controlled O 0
Trials O 0
ISRCTN54598675 O 0
. O 0

Registered O 0
17 O 0
August O 0
2007 O 0
. O 0

Rhabdomyolysis B-Disease 0
in O 0
a O 0
hepatitis B-Disease 0
C I-Disease 0
virus I-Disease 0
infected I-Disease 0
patient O 0
treated O 0
with O 0
telaprevir B-Chemical 0
and O 0
simvastatin B-Chemical 0
. O 0

A O 0
46 O 0
- O 0
year O 0
old O 0
man O 0
with O 0
a O 0
chronic O 0
hepatitis B-Disease 0
C I-Disease 0
virus I-Disease 0
infection I-Disease 0
received O 0
triple O 0
therapy O 0
with O 0
ribavirin B-Chemical 0
, O 0
pegylated B-Chemical 0
interferon I-Chemical 0
and O 0
telaprevir B-Chemical 0
. O 0

The O 0
patient O 0
also O 0
received O 0
simvastatin B-Chemical 0
. O 0

One O 0
month O 0
after O 0
starting O 0
the O 0
antiviral O 0
therapy O 0
, O 0
the O 0
patient O 0
was O 0
admitted O 0
to O 0
the O 0
hospital O 0
because O 0
he O 0
developed O 0
rhabdomyolysis B-Disease 0
. O 0

At O 0
admission O 0
simvastatin B-Chemical 0
and O 0
all O 0
antiviral O 0
drugs O 0
were O 0
discontinued O 0
because O 0
toxicity B-Disease 0
due O 0
to O 0
a O 0
drug O 0
- O 0
drug O 0
interaction O 0
was O 0
suspected O 0
. O 0

The O 0
creatine B-Chemical 0
kinase O 0
peaked O 0
at O 0
62 O 0
, O 0
246 O 0
IU O 0
/ O 0
L O 0
and O 0
the O 0
patient O 0
was O 0
treated O 0
with O 0
intravenous O 0
normal O 0
saline O 0
. O 0

The O 0
patient O 0
' O 0
s O 0
renal O 0
function O 0
remained O 0
unaffected O 0
. O 0

Fourteen O 0
days O 0
after O 0
hospitalization O 0
, O 0
creatine B-Chemical 0
kinase O 0
level O 0
had O 0
returned O 0
to O 0
230 O 0
IU O 0
/ O 0
L O 0
and O 0
the O 0
patient O 0
was O 0
discharged O 0
. O 0

Telaprevir B-Chemical 0
was O 0
considered O 0
the O 0
probable O 0
causative O 0
agent O 0
of O 0
an O 0
interaction O 0
with O 0
simvastatin B-Chemical 0
according O 0
to O 0
the O 0
Drug O 0
Interaction O 0
Probability O 0
Scale O 0
. O 0

The O 0
interaction O 0
is O 0
due O 0
to O 0
inhibition O 0
of O 0
CYP3A4 O 0
- O 0
mediated O 0
simvastatin B-Chemical 0
clearance O 0
. O 0

Simvastatin B-Chemical 0
plasma O 0
concentration O 0
increased O 0
30 O 0
times O 0
in O 0
this O 0
patient O 0
and O 0
statin B-Chemical 0
induced O 0
muscle B-Disease 0
toxicity I-Disease 0
is O 0
related O 0
to O 0
the O 0
concentration O 0
of O 0
the O 0
statin B-Chemical 0
in O 0
blood O 0
. O 0

In O 0
conclusion O 0
, O 0
with O 0
this O 0
case O 0
we O 0
illustrate O 0
that O 0
telaprevir B-Chemical 0
as O 0
well O 0
as O 0
statins B-Chemical 0
are O 0
susceptible O 0
to O 0
clinical O 0
relevant O 0
drug O 0
- O 0
drug O 0
interactions O 0
. O 0

Combination O 0
of O 0
bortezomib B-Chemical 0
, O 0
thalidomide B-Chemical 0
, O 0
and O 0
dexamethasone B-Chemical 0
( O 0
VTD O 0
) O 0
as O 0
a O 0
consolidation O 0
therapy O 0
after O 0
autologous O 0
stem O 0
cell O 0
transplantation O 0
for O 0
symptomatic O 0
multiple B-Disease 0
myeloma I-Disease 0
in O 0
Japanese O 0
patients O 0
. O 0

Consolidation O 0
therapy O 0
for O 0
patients O 0
with O 0
multiple B-Disease 0
myeloma I-Disease 0
( O 0
MM B-Disease 0
) O 0
has O 0
been O 0
widely O 0
adopted O 0
to O 0
improve O 0
treatment O 0
response O 0
following O 0
autologous O 0
stem O 0
cell O 0
transplantation O 0
. O 0

In O 0
this O 0
study O 0
, O 0
we O 0
retrospectively O 0
analyzed O 0
the O 0
safety O 0
and O 0
efficacy O 0
of O 0
combination O 0
regimen O 0
of O 0
bortezomib B-Chemical 0
, O 0
thalidomide B-Chemical 0
, O 0
and O 0
dexamethasone B-Chemical 0
( O 0
VTD O 0
) O 0
as O 0
consolidation O 0
therapy O 0
in O 0
24 O 0
Japanese O 0
patients O 0
with O 0
newly O 0
diagnosed O 0
MM B-Disease 0
. O 0

VTD O 0
consisted O 0
of O 0
bortezomib B-Chemical 0
at O 0
a O 0
dose O 0
of O 0
1 O 0
. O 0
3 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
and O 0
dexamethasone B-Chemical 0
at O 0
a O 0
dose O 0
of O 0
40 O 0
mg O 0
/ O 0
day O 0
on O 0
days O 0
1 O 0
, O 0
8 O 0
, O 0
15 O 0
, O 0
and O 0
22 O 0
of O 0
a O 0
35 O 0
- O 0
day O 0
cycle O 0
, O 0
with O 0
daily O 0
oral O 0
thalidomide B-Chemical 0
at O 0
a O 0
dose O 0
of O 0
100 O 0
mg O 0
/ O 0
day O 0
. O 0

Grade O 0
3 O 0
- O 0
4 O 0
neutropenia B-Disease 0
and O 0
thrombocytopenia B-Disease 0
were O 0
documented O 0
in O 0
four O 0
and O 0
three O 0
patients O 0
( O 0
17 O 0
and O 0
13 O 0
% O 0
) O 0
, O 0
respectively O 0
, O 0
but O 0
drug O 0
dose O 0
reduction O 0
due O 0
to O 0
cytopenia B-Disease 0
was O 0
not O 0
required O 0
in O 0
any O 0
case O 0
. O 0

Peripheral B-Disease 0
neuropathy I-Disease 0
was O 0
common O 0
( O 0
63 O 0
% O 0
) O 0
, O 0
but O 0
severe O 0
grade O 0
3 O 0
- O 0
4 O 0
peripheral B-Disease 0
neuropathy I-Disease 0
was O 0
not O 0
observed O 0
. O 0

Very O 0
good O 0
partial O 0
response O 0
or O 0
better O 0
response O 0
( O 0
> O 0
VGPR O 0
) O 0
rates O 0
before O 0
and O 0
after O 0
consolidation O 0
therapy O 0
were O 0
54 O 0
and O 0
79 O 0
% O 0
, O 0
respectively O 0
. O 0

Patients O 0
had O 0
a O 0
significant O 0
probability O 0
of O 0
improving O 0
from O 0
< O 0
VGPR O 0
before O 0
consolidation O 0
therapy O 0
to O 0
> O 0
VGPR O 0
after O 0
consolidation O 0
therapy O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
041 O 0
) O 0
. O 0

The O 0
VTD O 0
regimen O 0
may O 0
be O 0
safe O 0
and O 0
effective O 0
as O 0
a O 0
consolidation O 0
therapy O 0
in O 0
the O 0
treatment O 0
of O 0
MM O 0
in O 0
Japanese O 0
population O 0
. O 0

Conversion O 0
to O 0
sirolimus B-Chemical 0
ameliorates O 0
cyclosporine B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
in O 0
the O 0
rat O 0
: O 0
focus O 0
on O 0
serum O 0
, O 0
urine O 0
, O 0
gene O 0
, O 0
and O 0
protein O 0
renal O 0
expression O 0
biomarkers O 0
. O 0

Protocols O 0
of O 0
conversion O 0
from O 0
cyclosporin B-Chemical 0
A I-Chemical 0
( O 0
CsA B-Chemical 0
) O 0
to O 0
sirolimus B-Chemical 0
( O 0
SRL B-Chemical 0
) O 0
have O 0
been O 0
widely O 0
used O 0
in O 0
immunotherapy O 0
after O 0
transplantation O 0
to O 0
prevent O 0
CsA B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
, O 0
but O 0
the O 0
molecular O 0
mechanisms O 0
underlying O 0
these O 0
protocols O 0
remain O 0
nuclear O 0
. O 0

This O 0
study O 0
aimed O 0
to O 0
identify O 0
the O 0
molecular O 0
pathways O 0
and O 0
putative O 0
biomarkers O 0
of O 0
CsA B-Chemical 0
- O 0
to O 0
- O 0
SRL B-Chemical 0
conversion O 0
in O 0
a O 0
rat O 0
model O 0
. O 0

Four O 0
animal O 0
groups O 0
( O 0
n O 0
= O 0
6 O 0
) O 0
were O 0
tested O 0
during O 0
9 O 0
weeks O 0
: O 0
control O 0
, O 0
CsA B-Chemical 0
, O 0
SRL B-Chemical 0
, O 0
and O 0
conversion O 0
( O 0
CsA B-Chemical 0
for O 0
3 O 0
weeks O 0
followed O 0
by O 0
SRL B-Chemical 0
for O 0
6 O 0
weeks O 0
) O 0
. O 0

Classical O 0
and O 0
emergent O 0
serum O 0
, O 0
urinary O 0
, O 0
and O 0
kidney O 0
tissue O 0
( O 0
gene O 0
and O 0
protein O 0
expression O 0
) O 0
markers O 0
were O 0
assessed O 0
. O 0

Renal B-Disease 0
lesions I-Disease 0
were O 0
analyzed O 0
in O 0
hematoxylin B-Chemical 0
and O 0
eosin B-Chemical 0
, O 0
periodic O 0
acid O 0
- O 0
Schiff O 0
, O 0
and O 0
Masson O 0
' O 0
s O 0
trichrome O 0
stains O 0
. O 0

SRL B-Chemical 0
- O 0
treated O 0
rats O 0
presented O 0
proteinuria B-Disease 0
and O 0
NGAL O 0
( O 0
serum O 0
and O 0
urinary O 0
) O 0
as O 0
the O 0
best O 0
markers O 0
of O 0
renal B-Disease 0
impairment I-Disease 0
. O 0

Short O 0
CsA B-Chemical 0
treatment O 0
presented O 0
slight O 0
or O 0
even O 0
absent O 0
kidney B-Disease 0
lesions I-Disease 0
and O 0
TGF O 0
- O 0
b O 0
, O 0
NF O 0
- O 0
kb O 0
, O 0
mTOR O 0
, O 0
PCNA O 0
, O 0
TP53 O 0
, O 0
KIM O 0
- O 0
1 O 0
, O 0
and O 0
CTGF O 0
as O 0
relevant O 0
gene O 0
and O 0
protein O 0
changes O 0
. O 0

Prolonged O 0
CsA B-Chemical 0
exposure O 0
aggravated O 0
renal B-Disease 0
damage I-Disease 0
, O 0
without O 0
clear O 0
changes O 0
on O 0
the O 0
traditional O 0
markers O 0
, O 0
but O 0
with O 0
changes O 0
in O 0
serums O 0
TGF O 0
- O 0
b O 0
and O 0
IL O 0
- O 0
7 O 0
, O 0
TBARs O 0
clearance O 0
, O 0
and O 0
kidney O 0
TGF O 0
- O 0
b O 0
and O 0
mTOR O 0
. O 0

Conversion O 0
to O 0
SRL B-Chemical 0
prevented O 0
CsA B-Chemical 0
- O 0
induced O 0
renal B-Disease 0
damage I-Disease 0
evolution O 0
( O 0
absent O 0
/ O 0
mild O 0
grade O 0
lesions O 0
) O 0
, O 0
while O 0
NGAL O 0
( O 0
serum O 0
versus O 0
urine O 0
) O 0
seems O 0
to O 0
be O 0
a O 0
feasible O 0
biomarker O 0
of O 0
CsA B-Chemical 0
replacement O 0
to O 0
SRL B-Chemical 0
. O 0

Kinin O 0
B2 O 0
receptor O 0
deletion O 0
and O 0
blockage O 0
ameliorates O 0
cisplatin B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
renal I-Disease 0
injury I-Disease 0
. O 0

Cisplatin B-Chemical 0
treatment O 0
has O 0
been O 0
adopted O 0
in O 0
some O 0
chemotherapies O 0
; O 0
however O 0
, O 0
this O 0
drug O 0
can O 0
induce O 0
acute B-Disease 0
kidney I-Disease 0
injury I-Disease 0
due O 0
its O 0
ability O 0
to O 0
negatively O 0
affect O 0
renal O 0
function O 0
, O 0
augment O 0
serum O 0
levels O 0
of O 0
creatinine B-Chemical 0
and O 0
urea B-Chemical 0
, O 0
increase O 0
the O 0
acute B-Disease 0
tubular I-Disease 0
necrosis I-Disease 0
score O 0
and O 0
up O 0
- O 0
regulate O 0
cytokines O 0
( O 0
e O 0
. O 0
g O 0
. O 0
, O 0
IL O 0
- O 0
1b O 0
and O 0
TNF O 0
- O 0
a O 0
) O 0
. O 0

The O 0
kinin O 0
B2 O 0
receptor O 0
has O 0
been O 0
associated O 0
with O 0
the O 0
inflammation B-Disease 0
process O 0
, O 0
as O 0
well O 0
as O 0
the O 0
regulation O 0
of O 0
cytokine O 0
expression O 0
, O 0
and O 0
its O 0
deletion O 0
resulted O 0
in O 0
an O 0
improvement O 0
in O 0
the O 0
diabetic B-Disease 0
nephropathy I-Disease 0
status O 0
. O 0

To O 0
examine O 0
the O 0
role O 0
of O 0
the O 0
kinin O 0
B2 O 0
receptor O 0
in O 0
cisplatin B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
kidney I-Disease 0
injury I-Disease 0
, O 0
kinin O 0
B2 O 0
receptor O 0
knockout O 0
mice O 0
were O 0
challenged O 0
with O 0
cisplatin B-Chemical 0
. O 0

Additionally O 0
, O 0
WT O 0
mice O 0
were O 0
treated O 0
with O 0
a O 0
B2 O 0
receptor O 0
antagonist O 0
after O 0
cisplatin B-Chemical 0
administration O 0
. O 0

B2 O 0
receptor O 0
- O 0
deficient O 0
mice O 0
were O 0
less O 0
sensitive O 0
to O 0
this O 0
drug O 0
than O 0
the O 0
WT O 0
mice O 0
, O 0
as O 0
shown O 0
by O 0
reduced O 0
weight B-Disease 0
loss I-Disease 0
, O 0
better O 0
preservation O 0
of O 0
kidney O 0
function O 0
, O 0
down O 0
regulation O 0
of O 0
inflammatory O 0
cytokines O 0
and O 0
less O 0
acute B-Disease 0
tubular I-Disease 0
necrosis I-Disease 0
. O 0

Moreover O 0
, O 0
treatment O 0
with O 0
the O 0
kinin O 0
B2 O 0
receptor O 0
antagonist O 0
effectively O 0
reduced O 0
the O 0
levels O 0
of O 0
serum O 0
creatinine B-Chemical 0
and O 0
blood O 0
urea B-Chemical 0
after O 0
cisplatin B-Chemical 0
administration O 0
. O 0

Thus O 0
, O 0
our O 0
data O 0
suggest O 0
that O 0
the O 0
kinin O 0
B2 O 0
receptor O 0
is O 0
involved O 0
in O 0
cisplatin B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
kidney I-Disease 0
injury I-Disease 0
by O 0
mediating O 0
the O 0
necrotic B-Disease 0
process O 0
and O 0
the O 0
expression O 0
of O 0
inflammatory O 0
cytokines O 0
, O 0
thus O 0
resulting O 0
in O 0
declined O 0
renal O 0
function O 0
. O 0

These O 0
results O 0
highlight O 0
the O 0
kinin O 0
B2 O 0
receptor O 0
antagonist O 0
treatment O 0
in O 0
amelioration O 0
of O 0
nephrotoxicity B-Disease 0
induced O 0
by O 0
cisplatin B-Chemical 0
therapy O 0
. O 0

Safety O 0
and O 0
efficacy O 0
of O 0
fluocinolone B-Chemical 0
acetonide I-Chemical 0
intravitreal O 0
implant O 0
( O 0
0 O 0
. O 0
59 O 0
mg O 0
) O 0
in O 0
birdshot B-Disease 0
retinochoroidopathy I-Disease 0
. O 0

PURPOSE O 0
: O 0
To O 0
report O 0
the O 0
treatment O 0
outcomes O 0
of O 0
the O 0
fluocinolone B-Chemical 0
acetonide I-Chemical 0
intravitreal O 0
implant O 0
( O 0
0 O 0
. O 0
59 O 0
mg O 0
) O 0
in O 0
patients O 0
with O 0
birdshot B-Disease 0
retinochoroidopathy I-Disease 0
whose O 0
disease O 0
is O 0
refractory O 0
or O 0
intolerant O 0
to O 0
conventional O 0
immunomodulatory O 0
therapy O 0
. O 0

METHODS O 0
: O 0
A O 0
retrospective O 0
case O 0
series O 0
involving O 0
11 O 0
birdshot B-Disease 0
retinochoroidopathy I-Disease 0
patients O 0
( O 0
11 O 0
eyes O 0
) O 0
. O 0

Eleven O 0
patients O 0
( O 0
11 O 0
eyes O 0
) O 0
underwent O 0
surgery O 0
for O 0
fluocinolone B-Chemical 0
acetonide I-Chemical 0
implant O 0
( O 0
0 O 0
. O 0
59 O 0
mg O 0
) O 0
. O 0

Treatment O 0
outcomes O 0
of O 0
interest O 0
were O 0
noted O 0
at O 0
baseline O 0
, O 0
before O 0
fluocinolone B-Chemical 0
acetonide I-Chemical 0
implant O 0
, O 0
and O 0
then O 0
at O 0
6 O 0
months O 0
, O 0
1 O 0
year O 0
, O 0
2 O 0
years O 0
, O 0
3 O 0
years O 0
, O 0
and O 0
beyond O 0
3 O 0
years O 0
. O 0

Disease O 0
activity O 0
markers O 0
, O 0
including O 0
signs O 0
of O 0
ocular O 0
inflammation B-Disease 0
, O 0
evidence O 0
of O 0
retinal B-Disease 0
vasculitis I-Disease 0
, O 0
Swedish O 0
interactive O 0
threshold O 0
algorithm O 0
- O 0
short O 0
wavelength O 0
automated O 0
perimetry O 0
Humphrey O 0
visual O 0
field O 0
analysis O 0
, O 0
electroretinographic O 0
parameters O 0
, O 0
and O 0
optical O 0
coherence O 0
tomography O 0
were O 0
recorded O 0
. O 0

Data O 0
on O 0
occurrence O 0
of O 0
cataract B-Disease 0
and O 0
raised B-Disease 0
intraocular I-Disease 0
pressure I-Disease 0
were O 0
collected O 0
in O 0
all O 0
eyes O 0
. O 0

RESULTS O 0
: O 0
Intraocular O 0
inflammation B-Disease 0
was O 0
present O 0
in O 0
54 O 0
. O 0
5 O 0
, O 0
9 O 0
. O 0
9 O 0
, O 0
11 O 0
. O 0
1 O 0
, O 0
and O 0
0 O 0
% O 0
of O 0
patients O 0
at O 0
baseline O 0
, O 0
6 O 0
months O 0
, O 0
1 O 0
year O 0
, O 0
2 O 0
years O 0
, O 0
3 O 0
years O 0
, O 0
and O 0
beyond O 0
3 O 0
years O 0
after O 0
receiving O 0
the O 0
implant O 0
, O 0
respectively O 0
. O 0

Active O 0
vasculitis B-Disease 0
was O 0
noted O 0
in O 0
36 O 0
. O 0
3 O 0
% O 0
patients O 0
at O 0
baseline O 0
and O 0
0 O 0
% O 0
at O 0
3 O 0
years O 0
of O 0
follow O 0
- O 0
up O 0
. O 0

More O 0
than O 0
20 O 0
% O 0
( O 0
47 O 0
. O 0
61 O 0
- O 0
67 O 0
. O 0
2 O 0
% O 0
) O 0
reduction O 0
in O 0
central O 0
retinal O 0
thickness O 0
was O 0
noted O 0
in O 0
all O 0
patients O 0
with O 0
cystoid B-Disease 0
macular I-Disease 0
edema I-Disease 0
at O 0
6 O 0
months O 0
, O 0
1 O 0
year O 0
, O 0
2 O 0
years O 0
, O 0
and O 0
3 O 0
years O 0
postimplant O 0
. O 0

At O 0
baseline O 0
, O 0
54 O 0
. O 0
5 O 0
% O 0
patients O 0
were O 0
on O 0
immunomodulatory O 0
agents O 0
. O 0

This O 0
percentage O 0
decreased O 0
to O 0
45 O 0
. O 0
45 O 0
, O 0
44 O 0
. O 0
4 O 0
, O 0
and O 0
14 O 0
. O 0
28 O 0
% O 0
at O 0
1 O 0
year O 0
, O 0
2 O 0
years O 0
, O 0
and O 0
3 O 0
years O 0
postimplant O 0
, O 0
respectively O 0
. O 0

Adverse O 0
events O 0
included O 0
increased B-Disease 0
intraocular I-Disease 0
pressure I-Disease 0
( O 0
54 O 0
. O 0
5 O 0
% O 0
) O 0
and O 0
cataract B-Disease 0
formation O 0
( O 0
100 O 0
% O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
data O 0
suggest O 0
that O 0
fluocinolone B-Chemical 0
acetonide I-Chemical 0
implant O 0
( O 0
0 O 0
. O 0
59 O 0
mg O 0
) O 0
helps O 0
to O 0
control O 0
inflammation B-Disease 0
in O 0
otherwise O 0
treatment O 0
- O 0
refractory O 0
cases O 0
of O 0
birdshot B-Disease 0
retinochoroidopathy I-Disease 0
. O 0

It O 0
is O 0
associated O 0
with O 0
significant O 0
side O 0
effects O 0
of O 0
cataract B-Disease 0
and O 0
ocular B-Disease 0
hypertension I-Disease 0
requiring O 0
treatment O 0
. O 0

Optimal O 0
precurarizing O 0
dose O 0
of O 0
rocuronium B-Chemical 0
to O 0
decrease O 0
fasciculation B-Disease 0
and O 0
myalgia B-Disease 0
following O 0
succinylcholine B-Chemical 0
administration O 0
. O 0

BACKGROUND O 0
: O 0
Succinylcholine B-Chemical 0
commonly O 0
produces O 0
frequent O 0
adverse O 0
effects O 0
, O 0
including O 0
muscle B-Disease 0
fasciculation I-Disease 0
and O 0
myalgia B-Disease 0
. O 0

The O 0
current O 0
study O 0
identified O 0
the O 0
optimal O 0
dose O 0
of O 0
rocuronium B-Chemical 0
to O 0
prevent O 0
succinylcholine B-Chemical 0
- O 0
induced O 0
fasciculation B-Disease 0
and O 0
myalgia B-Disease 0
and O 0
evaluated O 0
the O 0
influence O 0
of O 0
rocuronium B-Chemical 0
on O 0
the O 0
speed O 0
of O 0
onset O 0
produced O 0
by O 0
succinylcholine B-Chemical 0
. O 0

METHODS O 0
: O 0
This O 0
randomized O 0
, O 0
double O 0
- O 0
blinded O 0
study O 0
was O 0
conducted O 0
in O 0
100 O 0
patients O 0
randomly O 0
allocated O 0
into O 0
five O 0
groups O 0
of O 0
20 O 0
patients O 0
each O 0
. O 0

Patients O 0
were O 0
randomized O 0
to O 0
receive O 0
0 O 0
. O 0
02 O 0
, O 0
0 O 0
. O 0
03 O 0
, O 0
0 O 0
. O 0
04 O 0
, O 0
0 O 0
. O 0
05 O 0
and O 0
0 O 0
. O 0
06 O 0
mg O 0
/ O 0
kg O 0
rocuronium B-Chemical 0
as O 0
a O 0
precurarizing O 0
dose O 0
. O 0

Neuromuscular O 0
monitoring O 0
after O 0
each O 0
precurarizing O 0
dose O 0
was O 0
recorded O 0
from O 0
the O 0
adductor O 0
pollicis O 0
muscle O 0
using O 0
acceleromyography O 0
with O 0
train O 0
- O 0
of O 0
- O 0
four O 0
stimulation O 0
of O 0
the O 0
ulnar O 0
nerve O 0
. O 0

All O 0
patients O 0
received O 0
succinylcholine B-Chemical 0
1 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
at O 0
2 O 0
minutes O 0
after O 0
the O 0
precurarization O 0
, O 0
and O 0
were O 0
assessed O 0
the O 0
incidence O 0
and O 0
severity O 0
of O 0
fasciculations B-Disease 0
, O 0
while O 0
myalgia B-Disease 0
was O 0
assessed O 0
at O 0
24 O 0
hours O 0
after O 0
surgery O 0
. O 0

RESULTS O 0
: O 0
The O 0
incidence O 0
and O 0
severity O 0
of O 0
visible O 0
muscle B-Disease 0
fasciculation I-Disease 0
was O 0
significantly O 0
less O 0
with O 0
increasing O 0
the O 0
amount O 0
of O 0
precurarizing O 0
dose O 0
of O 0
rocuronium B-Chemical 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Those O 0
of O 0
myalgia B-Disease 0
tend O 0
to O 0
decrease O 0
according O 0
to O 0
increasing O 0
the O 0
amount O 0
of O 0
precurarizing O 0
dose O 0
of O 0
rocuronium B-Chemical 0
, O 0
but O 0
there O 0
was O 0
no O 0
significance O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
072 O 0
) O 0
. O 0

The O 0
onset O 0
time O 0
of O 0
succinylcholine B-Chemical 0
was O 0
significantly O 0
longer O 0
with O 0
increasing O 0
the O 0
amount O 0
of O 0
precurarizing O 0
dose O 0
of O 0
rocuronium B-Chemical 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Precurarization O 0
with O 0
0 O 0
. O 0
04 O 0
mg O 0
/ O 0
kg O 0
rocuronium B-Chemical 0
was O 0
the O 0
optimal O 0
dose O 0
considering O 0
the O 0
reduction O 0
in O 0
the O 0
incidence O 0
and O 0
severity O 0
of O 0
fasciculation B-Disease 0
and O 0
myalgia B-Disease 0
with O 0
acceptable O 0
onset O 0
time O 0
, O 0
and O 0
the O 0
safe O 0
and O 0
effective O 0
precurarization O 0
. O 0

Absence O 0
of O 0
PKC O 0
- O 0
alpha O 0
attenuates O 0
lithium B-Chemical 0
- O 0
induced O 0
nephrogenic B-Disease 0
diabetes I-Disease 0
insipidus I-Disease 0
. O 0

Lithium B-Chemical 0
, O 0
an O 0
effective O 0
antipsychotic O 0
, O 0
induces O 0
nephrogenic B-Disease 0
diabetes I-Disease 0
insipidus I-Disease 0
( O 0
NDI B-Disease 0
) O 0
in O 0
40 O 0
% O 0
of O 0
patients O 0
. O 0

The O 0
decreased O 0
capacity O 0
to O 0
concentrate O 0
urine O 0
is O 0
likely O 0
due O 0
to O 0
lithium B-Chemical 0
acutely O 0
disrupting O 0
the O 0
cAMP B-Chemical 0
pathway O 0
and O 0
chronically O 0
reducing O 0
urea B-Chemical 0
transporter O 0
( O 0
UT O 0
- O 0
A1 O 0
) O 0
and O 0
water O 0
channel O 0
( O 0
AQP2 O 0
) O 0
expression O 0
in O 0
the O 0
inner O 0
medulla O 0
. O 0

Targeting O 0
an O 0
alternative O 0
signaling O 0
pathway O 0
, O 0
such O 0
as O 0
PKC O 0
- O 0
mediated O 0
signaling O 0
, O 0
may O 0
be O 0
an O 0
effective O 0
method O 0
of O 0
treating O 0
lithium B-Chemical 0
- O 0
induced O 0
polyuria B-Disease 0
. O 0

PKC O 0
- O 0
alpha O 0
null O 0
mice O 0
( O 0
PKCa O 0
KO O 0
) O 0
and O 0
strain O 0
- O 0
matched O 0
wild O 0
type O 0
( O 0
WT O 0
) O 0
controls O 0
were O 0
treated O 0
with O 0
lithium B-Chemical 0
for O 0
0 O 0
, O 0
3 O 0
or O 0
5 O 0
days O 0
. O 0

WT O 0
mice O 0
had O 0
increased O 0
urine O 0
output O 0
and O 0
lowered O 0
urine O 0
osmolality O 0
after O 0
3 O 0
and O 0
5 O 0
days O 0
of O 0
treatment O 0
whereas O 0
PKCa O 0
KO O 0
mice O 0
had O 0
no O 0
change O 0
in O 0
urine O 0
output O 0
or O 0
concentration O 0
. O 0

Western O 0
blot O 0
analysis O 0
revealed O 0
that O 0
AQP2 O 0
expression O 0
in O 0
medullary O 0
tissues O 0
was O 0
lowered O 0
after O 0
3 O 0
and O 0
5 O 0
days O 0
in O 0
WT O 0
mice O 0
; O 0
however O 0
, O 0
AQP2 O 0
was O 0
unchanged O 0
in O 0
PKCa O 0
KO O 0
. O 0

Similar O 0
results O 0
were O 0
observed O 0
with O 0
UT O 0
- O 0
A1 O 0
expression O 0
. O 0

Animals O 0
were O 0
also O 0
treated O 0
with O 0
lithium B-Chemical 0
for O 0
6 O 0
weeks O 0
. O 0

Lithium B-Chemical 0
- O 0
treated O 0
WT O 0
mice O 0
had O 0
19 O 0
- O 0
fold O 0
increased O 0
urine O 0
output O 0
whereas O 0
treated O 0
PKCa O 0
KO O 0
animals O 0
had O 0
a O 0
4 O 0
- O 0
fold O 0
increase O 0
in O 0
output O 0
. O 0

AQP2 O 0
and O 0
UT O 0
- O 0
A1 O 0
expression O 0
was O 0
lowered O 0
in O 0
6 O 0
week O 0
lithium B-Chemical 0
- O 0
treated O 0
WT O 0
animals O 0
whereas O 0
in O 0
treated O 0
PKCa O 0
KO O 0
mice O 0
, O 0
AQP2 O 0
was O 0
only O 0
reduced O 0
by O 0
2 O 0
- O 0
fold O 0
and O 0
UT O 0
- O 0
A1 O 0
expression O 0
was O 0
unaffected O 0
. O 0

Urinary O 0
sodium B-Chemical 0
, O 0
potassium B-Chemical 0
and O 0
calcium B-Chemical 0
were O 0
elevated O 0
in O 0
lithium B-Chemical 0
- O 0
fed O 0
WT O 0
but O 0
not O 0
in O 0
lithium B-Chemical 0
- O 0
fed O 0
PKCa O 0
KO O 0
mice O 0
. O 0

Our O 0
data O 0
show O 0
that O 0
ablation O 0
of O 0
PKCa O 0
preserves O 0
AQP2 O 0
and O 0
UT O 0
- O 0
A1 O 0
protein O 0
expression O 0
and O 0
localization O 0
in O 0
lithium B-Chemical 0
- O 0
induced O 0
NDI B-Disease 0
, O 0
and O 0
prevents O 0
the O 0
development O 0
of O 0
the O 0
severe O 0
polyuria B-Disease 0
associated O 0
with O 0
lithium B-Chemical 0
therapy O 0
. O 0

Is O 0
Dysguesia B-Disease 0
Going O 0
to O 0
be O 0
a O 0
Rare O 0
or O 0
a O 0
Common O 0
Side O 0
- O 0
effect O 0
of O 0
Amlodipine B-Chemical 0
? O 0

A O 0
very O 0
rare O 0
side O 0
- O 0
effect O 0
of O 0
amlodipine B-Chemical 0
is O 0
dysguesia B-Disease 0
. O 0

A O 0
review O 0
of O 0
the O 0
literature O 0
produced O 0
only O 0
one O 0
case O 0
. O 0

We O 0
report O 0
a O 0
case O 0
about O 0
a O 0
female O 0
with O 0
essential O 0
hypertension B-Disease 0
on O 0
drug O 0
treatment O 0
with O 0
amlodipine B-Chemical 0
developed O 0
loss B-Disease 0
of I-Disease 0
taste I-Disease 0
sensation I-Disease 0
. O 0

Condition O 0
moderately O 0
improved O 0
on O 0
stoppage O 0
of O 0
the O 0
drug O 0
for O 0
25 O 0
days O 0
. O 0

We O 0
conclude O 0
that O 0
amlodipine B-Chemical 0
can O 0
cause O 0
dysguesia B-Disease 0
. O 0

Here O 0
, O 0
we O 0
describe O 0
the O 0
clinical O 0
presentation O 0
and O 0
review O 0
the O 0
relevant O 0
literature O 0
on O 0
amlodipine B-Chemical 0
and O 0
dysguesia B-Disease 0
. O 0

Rhabdomyolysis B-Disease 0
in O 0
association O 0
with O 0
simvastatin B-Chemical 0
and O 0
dosage O 0
increment O 0
in O 0
clarithromycin B-Chemical 0
. O 0

Clarithromycin B-Chemical 0
is O 0
the O 0
most O 0
documented O 0
cytochrome O 0
P450 O 0
3A4 O 0
( O 0
CYP3A4 O 0
) O 0
inhibitor O 0
to O 0
cause O 0
an O 0
adverse O 0
interaction O 0
with O 0
simvastatin B-Chemical 0
. O 0

This O 0
particular O 0
case O 0
is O 0
of O 0
interest O 0
as O 0
rhabdomyolysis B-Disease 0
only O 0
occurred O 0
after O 0
an O 0
increase O 0
in O 0
the O 0
dose O 0
of O 0
clarithromycin B-Chemical 0
. O 0

The O 0
patient O 0
developed O 0
raised O 0
cardiac O 0
biomarkers O 0
without O 0
any O 0
obvious O 0
cardiac O 0
issues O 0
, O 0
a O 0
phenomenon O 0
that O 0
has O 0
been O 0
linked O 0
to O 0
rhabdomyolysis B-Disease 0
previously O 0
. O 0

To O 0
date O 0
, O 0
there O 0
has O 0
been O 0
no O 0
reported O 0
effect O 0
of O 0
rhabdomyolysis B-Disease 0
on O 0
the O 0
structure O 0
and O 0
function O 0
of O 0
cardiac O 0
muscle O 0
. O 0

Clinicians O 0
need O 0
to O 0
be O 0
aware O 0
of O 0
prescribing O 0
concomitant O 0
medications O 0
that O 0
increase O 0
the O 0
risk O 0
of O 0
myopathy B-Disease 0
or O 0
inhibit O 0
the O 0
CYP3A4 O 0
enzyme O 0
. O 0

Our O 0
case O 0
suggests O 0
that O 0
troponin O 0
elevation O 0
could O 0
be O 0
associated O 0
with O 0
statin B-Chemical 0
induced O 0
rhabdomyolysis B-Disease 0
, O 0
which O 0
may O 0
warrant O 0
further O 0
studies O 0
. O 0

Characterization O 0
of O 0
a O 0
novel O 0
BCHE O 0
" O 0
silent O 0
" O 0
allele O 0
: O 0
point O 0
mutation O 0
( O 0
p O 0
. O 0
Val204Asp O 0
) O 0
causes O 0
loss O 0
of O 0
activity O 0
and O 0
prolonged O 0
apnea B-Disease 0
with O 0
suxamethonium B-Chemical 0
. O 0

Butyrylcholinesterase B-Disease 0
deficiency I-Disease 0
is O 0
characterized O 0
by O 0
prolonged O 0
apnea B-Disease 0
after O 0
the O 0
use O 0
of O 0
muscle O 0
relaxants O 0
( O 0
suxamethonium B-Chemical 0
or O 0
mivacurium B-Chemical 0
) O 0
in O 0
patients O 0
who O 0
have O 0
mutations O 0
in O 0
the O 0
BCHE O 0
gene O 0
. O 0

Here O 0
, O 0
we O 0
report O 0
a O 0
case O 0
of O 0
prolonged O 0
neuromuscular O 0
block O 0
after O 0
administration O 0
of O 0
suxamethonium B-Chemical 0
leading O 0
to O 0
the O 0
discovery O 0
of O 0
a O 0
novel O 0
BCHE O 0
variant O 0
( O 0
c O 0
. O 0
695T O 0
> O 0
A O 0
, O 0
p O 0
. O 0
Val204Asp O 0
) O 0
. O 0

Inhibition O 0
studies O 0
, O 0
kinetic O 0
analysis O 0
and O 0
molecular O 0
dynamics O 0
were O 0
undertaken O 0
to O 0
understand O 0
how O 0
this O 0
mutation O 0
disrupts O 0
the O 0
catalytic O 0
triad O 0
and O 0
determines O 0
a O 0
" O 0
silent O 0
" O 0
phenotype O 0
. O 0

Low O 0
activity O 0
of O 0
patient O 0
plasma O 0
butyrylcholinesterase O 0
with O 0
butyrylthiocholine B-Chemical 0
( O 0
BTC B-Chemical 0
) O 0
and O 0
benzoylcholine B-Chemical 0
, O 0
and O 0
values O 0
of O 0
dibucaine B-Chemical 0
and O 0
fluoride B-Chemical 0
numbers O 0
fit O 0
with O 0
heterozygous O 0
atypical O 0
silent O 0
genotype O 0
. O 0

Electrophoretic O 0
analysis O 0
of O 0
plasma O 0
BChE O 0
of O 0
the O 0
proband O 0
and O 0
his O 0
mother O 0
showed O 0
that O 0
patient O 0
has O 0
a O 0
reduced O 0
amount O 0
of O 0
tetrameric O 0
enzyme O 0
in O 0
plasma O 0
and O 0
that O 0
minor O 0
fast O 0
- O 0
moving O 0
BChE O 0
components O 0
: O 0
monomer O 0
, O 0
dimer O 0
, O 0
and O 0
monomer O 0
- O 0
albumin O 0
conjugate O 0
are O 0
missing O 0
. O 0

Kinetic O 0
analysis O 0
showed O 0
that O 0
the O 0
p O 0
. O 0
Val204Asp O 0
/ O 0
p O 0
. O 0
Asp70Gly O 0
- O 0
p O 0
. O 0
Ala539Thr O 0
BChE O 0
displays O 0
a O 0
pure O 0
Michaelian O 0
behavior O 0
with O 0
BTC B-Chemical 0
as O 0
the O 0
substrate O 0
. O 0

Both O 0
catalytic O 0
parameters O 0
Km O 0
= O 0
265 O 0
uM O 0
for O 0
BTC B-Chemical 0
, O 0
two O 0
times O 0
higher O 0
than O 0
that O 0
of O 0
the O 0
atypical O 0
enzyme O 0
, O 0
and O 0
a O 0
low O 0
Vmax O 0
are O 0
consistent O 0
with O 0
the O 0
absence O 0
of O 0
activity O 0
against O 0
suxamethonium B-Chemical 0
. O 0

Molecular O 0
dynamic O 0
( O 0
MD O 0
) O 0
simulations O 0
showed O 0
that O 0
the O 0
overall O 0
effect O 0
of O 0
the O 0
mutation O 0
p O 0
. O 0
Val204Asp O 0
is O 0
disruption O 0
of O 0
hydrogen B-Chemical 0
bonding O 0
between O 0
Gln223 O 0
and O 0
Glu441 O 0
, O 0
leading O 0
Ser198 O 0
and O 0
His438 O 0
to O 0
move O 0
away O 0
from O 0
each O 0
other O 0
with O 0
subsequent O 0
disruption O 0
of O 0
the O 0
catalytic O 0
triad O 0
functionality O 0
regardless O 0
of O 0
the O 0
type O 0
of O 0
substrate O 0
. O 0

MD O 0
also O 0
showed O 0
that O 0
the O 0
enzyme O 0
volume O 0
is O 0
increased O 0
, O 0
suggesting O 0
a O 0
pre O 0
- O 0
denaturation O 0
state O 0
. O 0

This O 0
fits O 0
with O 0
the O 0
reduced O 0
concentration O 0
of O 0
p O 0
. O 0
Ala204Asp O 0
/ O 0
p O 0
. O 0
Asp70Gly O 0
- O 0
p O 0
. O 0
Ala539Thr O 0
tetrameric O 0
enzyme O 0
in O 0
the O 0
plasma O 0
and O 0
non O 0
- O 0
detectable O 0
fast O 0
moving O 0
- O 0
bands O 0
on O 0
electrophoresis O 0
gels O 0
. O 0

Delayed O 0
anemia B-Disease 0
after O 0
treatment O 0
with O 0
injectable O 0
artesunate B-Chemical 0
in O 0
the O 0
Democratic O 0
Republic O 0
of O 0
the O 0
Congo O 0
: O 0
a O 0
manageable O 0
issue O 0
. O 0

Cases O 0
of O 0
delayed O 0
hemolytic B-Disease 0
anemia I-Disease 0
have O 0
been O 0
described O 0
after O 0
treatment O 0
with O 0
injectable O 0
artesunate B-Chemical 0
, O 0
the O 0
current O 0
World O 0
Health O 0
Organization O 0
( O 0
WHO O 0
) O 0
- O 0
recommended O 0
first O 0
- O 0
line O 0
drug O 0
for O 0
the O 0
treatment O 0
of O 0
severe O 0
malaria B-Disease 0
. O 0

A O 0
total O 0
of O 0
350 O 0
patients O 0
( O 0
215 O 0
[ O 0
61 O 0
. O 0
4 O 0
% O 0
] O 0
< O 0
5 O 0
years O 0
of O 0
age O 0
and O 0
135 O 0
[ O 0
38 O 0
. O 0
6 O 0
% O 0
] O 0
> O 0
5 O 0
years O 0
of O 0
age O 0
) O 0
were O 0
followed O 0
- O 0
up O 0
after O 0
treatment O 0
with O 0
injectable O 0
artesunate B-Chemical 0
for O 0
severe O 0
malaria B-Disease 0
in O 0
hospitals O 0
and O 0
health O 0
centers O 0
of O 0
the O 0
Democratic O 0
Republic O 0
of O 0
the O 0
Congo O 0
. O 0

Complete O 0
series O 0
of O 0
hemoglobin O 0
( O 0
Hb O 0
) O 0
measurements O 0
were O 0
available O 0
for O 0
201 O 0
patients O 0
. O 0

A O 0
decrease O 0
in O 0
Hb O 0
levels O 0
between O 0
2 O 0
and O 0
5 O 0
g O 0
/ O 0
dL O 0
was O 0
detected O 0
in O 0
23 O 0
( O 0
11 O 0
. O 0
4 O 0
% O 0
) O 0
patients O 0
during O 0
the O 0
follow O 0
- O 0
up O 0
period O 0
. O 0

For O 0
five O 0
patients O 0
, O 0
Hb O 0
levels O 0
decreased O 0
below O 0
5 O 0
g O 0
/ O 0
dL O 0
during O 0
at O 0
least O 0
one O 0
follow O 0
- O 0
up O 0
visit O 0
. O 0

All O 0
cases O 0
of O 0
delayed O 0
anemia B-Disease 0
were O 0
clinically O 0
manageable O 0
and O 0
resolved O 0
within O 0
one O 0
month O 0
. O 0

Regulation O 0
of O 0
signal O 0
transducer O 0
and O 0
activator O 0
of O 0
transcription O 0
3 O 0
and O 0
apoptotic O 0
pathways O 0
by O 0
betaine B-Chemical 0
attenuates O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
acute O 0
myocardial B-Disease 0
injury I-Disease 0
in O 0
rats O 0
. O 0

The O 0
present O 0
study O 0
was O 0
designed O 0
to O 0
investigate O 0
the O 0
cardioprotective O 0
effects O 0
of O 0
betaine B-Chemical 0
on O 0
acute O 0
myocardial B-Disease 0
ischemia I-Disease 0
induced O 0
experimentally O 0
in O 0
rats O 0
focusing O 0
on O 0
regulation O 0
of O 0
signal O 0
transducer O 0
and O 0
activator O 0
of O 0
transcription O 0
3 O 0
( O 0
STAT3 O 0
) O 0
and O 0
apoptotic O 0
pathways O 0
as O 0
the O 0
potential O 0
mechanism O 0
underlying O 0
the O 0
drug O 0
effect O 0
. O 0

Male O 0
Sprague O 0
Dawley O 0
rats O 0
were O 0
treated O 0
with O 0
betaine B-Chemical 0
( O 0
100 O 0
, O 0
200 O 0
, O 0
and O 0
400 O 0
mg O 0
/ O 0
kg O 0
) O 0
orally O 0
for O 0
40 O 0
days O 0
. O 0

Acute O 0
myocardial B-Disease 0
ischemic I-Disease 0
injury I-Disease 0
was O 0
induced O 0
in O 0
rats O 0
by O 0
subcutaneous O 0
injection O 0
of O 0
isoproterenol B-Chemical 0
( O 0
85 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
for O 0
two O 0
consecutive O 0
days O 0
. O 0

Serum O 0
cardiac O 0
marker O 0
enzyme O 0
, O 0
histopathological O 0
variables O 0
and O 0
expression O 0
of O 0
protein O 0
levels O 0
were O 0
analyzed O 0
. O 0

Oral O 0
administration O 0
of O 0
betaine B-Chemical 0
( O 0
200 O 0
and O 0
400 O 0
mg O 0
/ O 0
kg O 0
) O 0
significantly O 0
reduced O 0
the O 0
level O 0
of O 0
cardiac O 0
marker O 0
enzyme O 0
in O 0
the O 0
serum O 0
and O 0
prevented O 0
left O 0
ventricular B-Disease 0
remodeling I-Disease 0
. O 0

Western O 0
blot O 0
analysis O 0
showed O 0
that O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
phosphorylation O 0
of O 0
STAT3 O 0
was O 0
maintained O 0
or O 0
further O 0
enhanced O 0
by O 0
betaine B-Chemical 0
treatment O 0
in O 0
myocardium O 0
. O 0

Furthermore O 0
, O 0
betaine B-Chemical 0
( O 0
200 O 0
and O 0
400 O 0
mg O 0
/ O 0
kg O 0
) O 0
treatment O 0
increased O 0
the O 0
ventricular O 0
expression O 0
of O 0
Bcl O 0
- O 0
2 O 0
and O 0
reduced O 0
the O 0
level O 0
of O 0
Bax O 0
, O 0
therefore O 0
causing O 0
a O 0
significant O 0
increase O 0
in O 0
the O 0
ratio O 0
of O 0
Bcl O 0
- O 0
2 O 0
/ O 0
Bax O 0
. O 0

The O 0
protective O 0
role O 0
of O 0
betaine B-Chemical 0
on O 0
myocardial B-Disease 0
damage I-Disease 0
was O 0
further O 0
confirmed O 0
by O 0
histopathological O 0
examination O 0
. O 0

In O 0
summary O 0
, O 0
our O 0
results O 0
showed O 0
that O 0
betaine B-Chemical 0
pretreatment O 0
attenuated O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
acute O 0
myocardial B-Disease 0
ischemia I-Disease 0
via O 0
the O 0
regulation O 0
of O 0
STAT3 O 0
and O 0
apoptotic O 0
pathways O 0
. O 0

Quetiapine B-Chemical 0
- O 0
induced O 0
neutropenia B-Disease 0
in O 0
a O 0
bipolar B-Disease 0
patient O 0
with O 0
hepatocellular B-Disease 0
carcinoma I-Disease 0
. O 0

OBJECTIVE O 0
: O 0
Quetiapine B-Chemical 0
is O 0
a O 0
dibenzothiazepine O 0
derivative O 0
, O 0
similar O 0
to O 0
clozapine B-Chemical 0
, O 0
which O 0
has O 0
the O 0
highest O 0
risk O 0
of O 0
causing O 0
blood B-Disease 0
dyscrasias I-Disease 0
, O 0
especially O 0
neutropenia B-Disease 0
. O 0

There O 0
are O 0
some O 0
case O 0
reports O 0
about O 0
this O 0
side O 0
effect O 0
of O 0
quetiapine B-Chemical 0
, O 0
but O 0
possible O 0
risk O 0
factors O 0
are O 0
seldom O 0
discussed O 0
and O 0
identified O 0
. O 0

A O 0
case O 0
of O 0
a O 0
patient O 0
with O 0
hepatocellular B-Disease 0
carcinoma I-Disease 0
that O 0
developed O 0
neutropenia B-Disease 0
after O 0
treatment O 0
with O 0
quetiapine B-Chemical 0
is O 0
described O 0
here O 0
. O 0

CASE O 0
REPORT O 0
: O 0
A O 0
62 O 0
- O 0
year O 0
- O 0
old O 0
Taiwanese O 0
widow O 0
with O 0
bipolar B-Disease 0
disorder I-Disease 0
was O 0
diagnosed O 0
with O 0
hepatocellular B-Disease 0
carcinoma I-Disease 0
at O 0
age O 0
60 O 0
. O 0

She O 0
developed O 0
leucopenia B-Disease 0
after O 0
being O 0
treated O 0
with O 0
quetiapine B-Chemical 0
. O 0

After O 0
quetiapine B-Chemical 0
was O 0
discontinued O 0
, O 0
her O 0
white O 0
blood O 0
cell O 0
count O 0
returned O 0
to O 0
normal O 0
. O 0

CONCLUSIONS O 0
: O 0
Although O 0
neutropenia B-Disease 0
is O 0
not O 0
a O 0
common O 0
side O 0
effect O 0
of O 0
quetiapine B-Chemical 0
, O 0
physicians O 0
should O 0
be O 0
cautious O 0
about O 0
its O 0
presentation O 0
and O 0
associated O 0
risk O 0
factors O 0
. O 0

Hepatic B-Disease 0
dysfunction I-Disease 0
may O 0
be O 0
one O 0
of O 0
the O 0
possible O 0
risk O 0
factors O 0
, O 0
and O 0
concomitant O 0
fever B-Disease 0
may O 0
be O 0
a O 0
diagnostic O 0
marker O 0
for O 0
adverse O 0
reaction O 0
to O 0
quetiapine B-Chemical 0
. O 0

Lateral O 0
antebrachial O 0
cutaneous O 0
neuropathy B-Disease 0
after O 0
steroid B-Chemical 0
injection O 0
at O 0
lateral O 0
epicondyle O 0
. O 0

BACKGROUND O 0
AND O 0
OBJECTIVES O 0
: O 0
This O 0
report O 0
aimed O 0
to O 0
present O 0
a O 0
case O 0
of O 0
lateral O 0
antebrachial O 0
cutaneous O 0
neuropathy B-Disease 0
( O 0
LACNP O 0
) O 0
that O 0
occurred O 0
after O 0
a O 0
steroid B-Chemical 0
injection O 0
in O 0
the O 0
lateral O 0
epicondyle O 0
to O 0
treat O 0
lateral B-Disease 0
epicondylitis I-Disease 0
in O 0
a O 0
40 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
. O 0

MATERIAL O 0
AND O 0
METHOD O 0
: O 0
A O 0
40 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
presented O 0
with O 0
decreased O 0
sensation O 0
and O 0
paresthesia B-Disease 0
over O 0
her O 0
right O 0
lateral O 0
forearm O 0
; O 0
the O 0
paresthesia B-Disease 0
had O 0
occurred O 0
after O 0
a O 0
steroid B-Chemical 0
injection O 0
in O 0
the O 0
right O 0
lateral O 0
epicondyle O 0
3 O 0
months O 0
before O 0
. O 0

Her O 0
sensation O 0
of O 0
light O 0
touch O 0
and O 0
pain B-Disease 0
was O 0
diminished O 0
over O 0
the O 0
lateral O 0
side O 0
of O 0
the O 0
right O 0
forearm O 0
and O 0
wrist O 0
area O 0
. O 0

RESULTS O 0
: O 0
The O 0
sensory O 0
action O 0
potential O 0
amplitude O 0
of O 0
the O 0
right O 0
lateral O 0
antebrachial O 0
cutaneous O 0
nerve O 0
( O 0
LACN O 0
) O 0
( O 0
6 O 0
. O 0
2 O 0
uV O 0
) O 0
was O 0
lower O 0
than O 0
that O 0
of O 0
the O 0
left O 0
( O 0
13 O 0
. O 0
1 O 0
uV O 0
) O 0
. O 0

The O 0
difference O 0
of O 0
amplitude O 0
between O 0
both O 0
sides O 0
was O 0
significant O 0
because O 0
there O 0
was O 0
more O 0
than O 0
a O 0
50 O 0
% O 0
reduction O 0
. O 0

She O 0
was O 0
diagnosed O 0
with O 0
right O 0
LACNP O 0
( O 0
mainly O 0
axonal O 0
involvement O 0
) O 0
on O 0
the O 0
basis O 0
of O 0
the O 0
clinical O 0
manifestation O 0
and O 0
the O 0
electrodiagnostic O 0
findings O 0
. O 0

Her O 0
symptoms O 0
improved O 0
through O 0
physical O 0
therapy O 0
but O 0
persisted O 0
to O 0
some O 0
degree O 0
. O 0

CONCLUSION O 0
: O 0
This O 0
report O 0
describes O 0
the O 0
case O 0
of O 0
a O 0
woman O 0
with O 0
LACNP O 0
that O 0
developed O 0
after O 0
a O 0
steroid B-Chemical 0
injection O 0
for O 0
the O 0
treatment O 0
of O 0
lateral B-Disease 0
epicondylitis I-Disease 0
. O 0

An O 0
electrodiagnostic O 0
study O 0
, O 0
including O 0
a O 0
nerve O 0
conduction O 0
study O 0
of O 0
the O 0
LACN O 0
, O 0
was O 0
helpful O 0
to O 0
diagnose O 0
right O 0
LACNP O 0
and O 0
to O 0
find O 0
the O 0
passage O 0
of O 0
the O 0
LACN O 0
on O 0
the O 0
lateral O 0
epicondyle O 0
. O 0

Curcumin B-Chemical 0
prevents O 0
maleate B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
: O 0
relation O 0
to O 0
hemodynamic O 0
alterations O 0
, O 0
oxidative O 0
stress O 0
, O 0
mitochondrial O 0
oxygen B-Chemical 0
consumption O 0
and O 0
activity O 0
of O 0
respiratory O 0
complex O 0
I O 0
. O 0

The O 0
potential O 0
protective O 0
effect O 0
of O 0
the O 0
dietary O 0
antioxidant O 0
curcumin B-Chemical 0
( O 0
120 O 0
mg O 0
/ O 0
Kg O 0
/ O 0
day O 0
for O 0
6 O 0
days O 0
) O 0
against O 0
the O 0
renal B-Disease 0
injury I-Disease 0
induced O 0
by O 0
maleate B-Chemical 0
was O 0
evaluated O 0
. O 0

Tubular O 0
proteinuria B-Disease 0
and O 0
oxidative O 0
stress O 0
were O 0
induced O 0
by O 0
a O 0
single O 0
injection O 0
of O 0
maleate B-Chemical 0
( O 0
400 O 0
mg O 0
/ O 0
kg O 0
) O 0
in O 0
rats O 0
. O 0

Maleate B-Chemical 0
- O 0
induced O 0
renal B-Disease 0
injury I-Disease 0
included O 0
increase O 0
in O 0
renal O 0
vascular O 0
resistance O 0
and O 0
in O 0
the O 0
urinary O 0
excretion O 0
of O 0
total O 0
protein O 0
, O 0
glucose B-Chemical 0
, O 0
sodium B-Chemical 0
, O 0
neutrophil O 0
gelatinase O 0
- O 0
associated O 0
lipocalin O 0
( O 0
NGAL O 0
) O 0
and O 0
N O 0
- O 0
acetyl O 0
b O 0
- O 0
D O 0
- O 0
glucosaminidase O 0
( O 0
NAG O 0
) O 0
, O 0
upregulation O 0
of O 0
kidney B-Disease 0
injury I-Disease 0
molecule O 0
( O 0
KIM O 0
) O 0
- O 0
1 O 0
, O 0
decrease O 0
in O 0
renal O 0
blood O 0
flow O 0
and O 0
claudin O 0
- O 0
2 O 0
expression O 0
besides O 0
of O 0
necrosis B-Disease 0
and O 0
apoptosis O 0
of O 0
tubular O 0
cells O 0
on O 0
24 O 0
h O 0
. O 0

Oxidative O 0
stress O 0
was O 0
determined O 0
by O 0
measuring O 0
the O 0
oxidation O 0
of O 0
lipids O 0
and O 0
proteins O 0
and O 0
diminution O 0
in O 0
renal O 0
Nrf2 O 0
levels O 0
. O 0

Studies O 0
were O 0
also O 0
conducted O 0
in O 0
renal O 0
epithelial O 0
LLC O 0
- O 0
PK1 O 0
cells O 0
and O 0
in O 0
mitochondria O 0
isolated O 0
from O 0
kidneys O 0
of O 0
all O 0
the O 0
experimental O 0
groups O 0
. O 0

Maleate B-Chemical 0
induced O 0
cell O 0
damage O 0
and O 0
reactive O 0
oxygen B-Chemical 0
species O 0
( O 0
ROS O 0
) O 0
production O 0
in O 0
LLC O 0
- O 0
PK1 O 0
cells O 0
in O 0
culture O 0
. O 0

In O 0
addition O 0
, O 0
maleate B-Chemical 0
treatment O 0
reduced O 0
oxygen B-Chemical 0
consumption O 0
in O 0
ADP B-Chemical 0
- O 0
stimulated O 0
mitochondria O 0
and O 0
diminished O 0
respiratory O 0
control O 0
index O 0
when O 0
using O 0
malate B-Chemical 0
/ O 0
glutamate B-Chemical 0
as O 0
substrate O 0
. O 0

The O 0
activities O 0
of O 0
both O 0
complex O 0
I O 0
and O 0
aconitase O 0
were O 0
also O 0
diminished O 0
. O 0

All O 0
the O 0
above O 0
- O 0
described O 0
alterations O 0
were O 0
prevented O 0
by O 0
curcumin B-Chemical 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
curcumin B-Chemical 0
is O 0
able O 0
to O 0
attenuate O 0
in O 0
vivo O 0
maleate B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
and O 0
in O 0
vitro O 0
cell O 0
damage O 0
. O 0

The O 0
in O 0
vivo O 0
protection O 0
was O 0
associated O 0
to O 0
the O 0
prevention O 0
of O 0
oxidative O 0
stress O 0
and O 0
preservation O 0
of O 0
mitochondrial O 0
oxygen B-Chemical 0
consumption O 0
and O 0
activity O 0
of O 0
respiratory O 0
complex O 0
I O 0
, O 0
and O 0
the O 0
in O 0
vitro O 0
protection O 0
was O 0
associated O 0
to O 0
the O 0
prevention O 0
of O 0
ROS O 0
production O 0
. O 0

Anticonvulsant O 0
actions O 0
of O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
on O 0
the O 0
lithium B-Chemical 0
- O 0
pilocarpine B-Chemical 0
model O 0
of O 0
status B-Disease 0
epilepticus I-Disease 0
in O 0
rats O 0
. O 0

MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
, O 0
a O 0
noncompetitive O 0
N B-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
- I-Chemical 0
D I-Chemical 0
- I-Chemical 0
aspartate I-Chemical 0
( O 0
NMDA B-Chemical 0
) O 0
receptor O 0
antagonist O 0
, O 0
was O 0
tested O 0
for O 0
anticonvulsant O 0
effects O 0
in O 0
rats O 0
using O 0
two O 0
seizure B-Disease 0
models O 0
, O 0
coadministration O 0
of O 0
lithium B-Chemical 0
and O 0
pilocarpine B-Chemical 0
and O 0
administration O 0
of O 0
a O 0
high O 0
dose O 0
of O 0
pilocarpine B-Chemical 0
alone O 0
. O 0

Three O 0
major O 0
results O 0
are O 0
reported O 0
. O 0

First O 0
, O 0
pretreatment O 0
with O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
produced O 0
an O 0
effective O 0
and O 0
dose O 0
- O 0
dependent O 0
anticonvulsant O 0
action O 0
with O 0
the O 0
lithium B-Chemical 0
- O 0
pilocarpine B-Chemical 0
model O 0
but O 0
not O 0
with O 0
rats O 0
treated O 0
with O 0
pilocarpine B-Chemical 0
alone O 0
, O 0
suggesting O 0
that O 0
different O 0
biochemical O 0
mechanisms O 0
control O 0
seizures B-Disease 0
in O 0
these O 0
two O 0
models O 0
. O 0

Second O 0
, O 0
the O 0
anticonvulsant O 0
effect O 0
of O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
in O 0
the O 0
lithium B-Chemical 0
- O 0
pilocarpine B-Chemical 0
model O 0
only O 0
occurred O 0
after O 0
initial O 0
periods O 0
of O 0
seizure B-Disease 0
activity O 0
. O 0

This O 0
observation O 0
is O 0
suggested O 0
to O 0
be O 0
an O 0
in O 0
vivo O 0
demonstration O 0
of O 0
the O 0
conclusion O 0
derived O 0
from O 0
in O 0
vitro O 0
experiments O 0
that O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
binding O 0
requires O 0
agonist O 0
- O 0
induced O 0
opening O 0
of O 0
the O 0
channel O 0
sites O 0
of O 0
the O 0
NMDA B-Chemical 0
receptor O 0
. O 0

Third O 0
, O 0
although O 0
it O 0
is O 0
relatively O 0
easy O 0
to O 0
block O 0
seizures B-Disease 0
induced O 0
by O 0
lithium B-Chemical 0
and O 0
pilocarpine B-Chemical 0
by O 0
administration O 0
of O 0
anticonvulsants O 0
prior O 0
to O 0
pilocarpine B-Chemical 0
, O 0
it O 0
is O 0
more O 0
difficult O 0
to O 0
terminate O 0
ongoing O 0
status B-Disease 0
epilepticus I-Disease 0
and O 0
block O 0
the O 0
lethality O 0
of O 0
the O 0
seizures B-Disease 0
. O 0

Administration O 0
of O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
30 O 0
or O 0
60 O 0
min O 0
after O 0
pilocarpine B-Chemical 0
, O 0
i O 0
. O 0
e O 0
. O 0
, O 0
during O 0
status B-Disease 0
epilepticus I-Disease 0
, O 0
gradually O 0
reduced O 0
electrical O 0
and O 0
behavioral O 0
seizure B-Disease 0
activity O 0
and O 0
greatly O 0
enhanced O 0
the O 0
survival O 0
rate O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
activation O 0
of O 0
NMDA B-Chemical 0
receptors O 0
plays O 0
an O 0
important O 0
role O 0
in O 0
status B-Disease 0
epilepticus I-Disease 0
and O 0
brain B-Disease 0
damage I-Disease 0
in O 0
the O 0
lithium B-Chemical 0
- O 0
pilocarpine B-Chemical 0
model O 0
. O 0

This O 0
was O 0
further O 0
supported O 0
by O 0
results O 0
showing O 0
that O 0
nonconvulsive O 0
doses O 0
of O 0
NMDA B-Chemical 0
and O 0
pilocarpine B-Chemical 0
were O 0
synergistic O 0
, O 0
resulting O 0
in O 0
status B-Disease 0
epilepticus I-Disease 0
and O 0
subsequent O 0
mortality O 0
. O 0

Continuous O 0
infusion O 0
tobramycin B-Chemical 0
combined O 0
with O 0
carbenicillin B-Chemical 0
for O 0
infections B-Disease 0
in O 0
cancer B-Disease 0
patients O 0
. O 0

The O 0
cure O 0
rate O 0
of O 0
infections B-Disease 0
in O 0
cancer B-Disease 0
patients O 0
is O 0
adversely O 0
affected O 0
by O 0
neutropenia B-Disease 0
( O 0
less O 0
than O 0
1 O 0
, O 0
000 O 0
/ O 0
mm3 O 0
) O 0
. O 0

In O 0
particular O 0
, O 0
patients O 0
with O 0
severe O 0
neutropenia B-Disease 0
( O 0
less O 0
than O 0
100 O 0
/ O 0
mm3 O 0
) O 0
have O 0
shown O 0
a O 0
poor O 0
response O 0
to O 0
antibiotics O 0
. O 0

To O 0
overcome O 0
the O 0
adverse O 0
effects O 0
of O 0
neutropenia B-Disease 0
, O 0
tobramycin B-Chemical 0
was O 0
given O 0
by O 0
continuous O 0
infusion O 0
and O 0
combined O 0
with O 0
intermittent O 0
carbenicillin B-Chemical 0
. O 0

Tobramycin B-Chemical 0
was O 0
given O 0
to O 0
a O 0
total O 0
daily O 0
dose O 0
of O 0
300 O 0
mg O 0
/ O 0
m2 O 0
and O 0
carbenicillin B-Chemical 0
was O 0
given O 0
at O 0
a O 0
dose O 0
of O 0
5 O 0
gm O 0
every O 0
four O 0
hours O 0
. O 0

There O 0
were O 0
125 O 0
infectious O 0
episodes O 0
in O 0
116 O 0
cancer B-Disease 0
patients O 0
receiving O 0
myelosuppressive O 0
chemotherapy O 0
. O 0

The O 0
overall O 0
cure O 0
rate O 0
was O 0
70 O 0
% O 0
. O 0

Pneumonia B-Disease 0
was O 0
the O 0
most O 0
common O 0
infection B-Disease 0
and O 0
61 O 0
% O 0
of O 0
59 O 0
episodes O 0
were O 0
cured O 0
. O 0

Gram O 0
- O 0
negative O 0
bacilli O 0
were O 0
the O 0
most O 0
common O 0
causative O 0
organisms O 0
and O 0
69 O 0
% O 0
of O 0
these O 0
infections B-Disease 0
were O 0
cured O 0
. O 0

The O 0
most O 0
common O 0
pathogen O 0
was O 0
Klebsiella O 0
pneumoniae B-Disease 0
and O 0
this O 0
, O 0
together O 0
with O 0
Escherichia O 0
coli O 0
and O 0
Pseudomonas O 0
aeruginosa O 0
, O 0
accounted O 0
for O 0
74 O 0
% O 0
of O 0
all O 0
gram B-Disease 0
- I-Disease 0
negative I-Disease 0
bacillary I-Disease 0
infections I-Disease 0
. O 0

Response O 0
was O 0
not O 0
influenced O 0
by O 0
the O 0
initial O 0
neutrophil O 0
count O 0
, O 0
with O 0
a O 0
62 O 0
% O 0
cure O 0
rate O 0
for O 0
39 O 0
episodes O 0
associated O 0
with O 0
severe O 0
neutropenia B-Disease 0
. O 0

However O 0
, O 0
failure O 0
of O 0
the O 0
neutrophil O 0
count O 0
to O 0
increase O 0
during O 0
therapy O 0
adversely O 0
affected O 0
response O 0
. O 0

Azotemia B-Disease 0
was O 0
the O 0
major O 0
side O 0
effect O 0
recognized O 0
, O 0
and O 0
it O 0
occurred O 0
in O 0
11 O 0
% O 0
of O 0
episodes O 0
. O 0

Major O 0
azotemia B-Disease 0
( O 0
serum O 0
creatinine B-Chemical 0
greater O 0
than O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
dl O 0
or O 0
BUN O 0
greater O 0
than O 0
50 O 0
mg O 0
/ O 0
dl O 0
) O 0
occurred O 0
in O 0
only O 0
2 O 0
% O 0
. O 0

Azotemia B-Disease 0
was O 0
not O 0
related O 0
to O 0
duration O 0
of O 0
therapy O 0
or O 0
serum O 0
tobramycin B-Chemical 0
concentration O 0
. O 0

This O 0
antibiotic O 0
regimen O 0
showed O 0
both O 0
therapeutic O 0
efficacy O 0
and O 0
acceptable O 0
renal B-Disease 0
toxicity I-Disease 0
for O 0
these O 0
patients O 0
. O 0

Incidence O 0
of O 0
solid O 0
tumours B-Disease 0
among O 0
pesticide O 0
applicators O 0
exposed O 0
to O 0
the O 0
organophosphate B-Chemical 0
insecticide O 0
diazinon B-Chemical 0
in O 0
the O 0
Agricultural O 0
Health O 0
Study O 0
: O 0
an O 0
updated O 0
analysis O 0
. O 0

OBJECTIVE O 0
: O 0
Diazinon B-Chemical 0
, O 0
a O 0
common O 0
organophosphate B-Chemical 0
insecticide O 0
with O 0
genotoxic O 0
properties O 0
, O 0
was O 0
previously O 0
associated O 0
with O 0
lung B-Disease 0
cancer I-Disease 0
in O 0
the O 0
Agricultural O 0
Health O 0
Study O 0
( O 0
AHS O 0
) O 0
cohort O 0
, O 0
but O 0
few O 0
other O 0
epidemiological O 0
studies O 0
have O 0
examined O 0
diazinon B-Chemical 0
- O 0
associated O 0
cancer B-Disease 0
risk O 0
. O 0

We O 0
used O 0
updated O 0
diazinon B-Chemical 0
exposure O 0
and O 0
cancer B-Disease 0
incidence O 0
information O 0
to O 0
evaluate O 0
solid O 0
tumour B-Disease 0
risk O 0
in O 0
the O 0
AHS O 0
. O 0

METHODS O 0
: O 0
Male O 0
pesticide O 0
applicators O 0
in O 0
Iowa O 0
and O 0
North O 0
Carolina O 0
reported O 0
lifetime O 0
diazinon B-Chemical 0
use O 0
at O 0
enrolment O 0
( O 0
1993 O 0
- O 0
1997 O 0
) O 0
and O 0
follow O 0
- O 0
up O 0
( O 0
1998 O 0
- O 0
2005 O 0
) O 0
; O 0
cancer B-Disease 0
incidence O 0
was O 0
assessed O 0
through O 0
2010 O 0
( O 0
North O 0
Carolina O 0
) O 0
/ O 0
2011 O 0
( O 0
Iowa O 0
) O 0
. O 0

Among O 0
applicators O 0
with O 0
usage O 0
information O 0
sufficient O 0
to O 0
evaluate O 0
exposure O 0
- O 0
response O 0
patterns O 0
, O 0
we O 0
used O 0
Poisson O 0
regression O 0
to O 0
estimate O 0
adjusted O 0
rate O 0
ratios O 0
( O 0
RRs O 0
) O 0
and O 0
95 O 0
% O 0
CI O 0
for O 0
cancer B-Disease 0
sites O 0
with O 0
> O 0
10 O 0
exposed O 0
cases O 0
for O 0
both O 0
lifetime O 0
( O 0
LT O 0
) O 0
exposure O 0
days O 0
and O 0
intensity O 0
- O 0
weighted O 0
( O 0
IW O 0
) O 0
lifetime O 0
exposure O 0
days O 0
( O 0
accounting O 0
for O 0
factors O 0
impacting O 0
exposure O 0
) O 0
. O 0

RESULTS O 0
: O 0
We O 0
observed O 0
elevated O 0
lung B-Disease 0
cancer I-Disease 0
risks O 0
( O 0
N O 0
= O 0
283 O 0
) O 0
among O 0
applicators O 0
with O 0
the O 0
greatest O 0
number O 0
of O 0
LT O 0
( O 0
RR O 0
= O 0
1 O 0
. O 0
60 O 0
; O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
11 O 0
to O 0
2 O 0
. O 0
31 O 0
; O 0
Ptrend O 0
= O 0
0 O 0
. O 0
02 O 0
) O 0
and O 0
IW O 0
days O 0
of O 0
diazinon B-Chemical 0
use O 0
( O 0
RR O 0
= O 0
1 O 0
. O 0
41 O 0
; O 0
95 O 0
% O 0
CI O 0
0 O 0
. O 0
98 O 0
to O 0
2 O 0
. O 0
04 O 0
; O 0
Ptrend O 0
= O 0
0 O 0
. O 0
08 O 0
) O 0
. O 0

Kidney B-Disease 0
cancer I-Disease 0
( O 0
N O 0
= O 0
94 O 0
) O 0
risks O 0
were O 0
non O 0
- O 0
significantly O 0
elevated O 0
( O 0
RRLT O 0
days O 0
= O 0
1 O 0
. O 0
77 O 0
; O 0
95 O 0
% O 0
CI O 0
0 O 0
. O 0
90 O 0
to O 0
3 O 0
. O 0
51 O 0
; O 0
Ptrend O 0
= O 0
0 O 0
. O 0
09 O 0
; O 0
RRIW O 0
days O 0
1 O 0
. O 0
37 O 0
; O 0
95 O 0
% O 0
CI O 0
0 O 0
. O 0
64 O 0
to O 0
2 O 0
. O 0
92 O 0
; O 0
Ptrend O 0
= O 0
0 O 0
. O 0
50 O 0
) O 0
, O 0
as O 0
were O 0
risks O 0
for O 0
aggressive O 0
prostate B-Disease 0
cancer I-Disease 0
( O 0
N O 0
= O 0
656 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Our O 0
updated O 0
evaluation O 0
of O 0
diazinon B-Chemical 0
provides O 0
additional O 0
evidence O 0
of O 0
an O 0
association O 0
with O 0
lung B-Disease 0
cancer I-Disease 0
risk O 0
. O 0

Newly O 0
identified O 0
links O 0
to O 0
kidney B-Disease 0
cancer I-Disease 0
and O 0
associations O 0
with O 0
aggressive O 0
prostate B-Disease 0
cancer I-Disease 0
require O 0
further O 0
evaluation O 0
. O 0

Associations O 0
of O 0
Ozone B-Chemical 0
and O 0
PM2 O 0
. O 0
5 O 0
Concentrations O 0
With O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
Disease I-Disease 0
Among O 0
Participants O 0
in O 0
the O 0
Agricultural O 0
Health O 0
Study O 0
. O 0

OBJECTIVE O 0
: O 0
This O 0
study O 0
describes O 0
associations O 0
of O 0
ozone B-Chemical 0
and O 0
fine O 0
particulate B-Chemical 0
matter I-Chemical 0
with O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
observed O 0
among O 0
farmers O 0
in O 0
North O 0
Carolina O 0
and O 0
Iowa O 0
. O 0

METHODS O 0
: O 0
We O 0
used O 0
logistic O 0
regression O 0
to O 0
determine O 0
the O 0
associations O 0
of O 0
these O 0
pollutants O 0
with O 0
self O 0
- O 0
reported O 0
, O 0
doctor O 0
- O 0
diagnosed O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

Daily O 0
predicted O 0
pollutant O 0
concentrations O 0
were O 0
used O 0
to O 0
derive O 0
surrogates O 0
of O 0
long O 0
- O 0
term O 0
exposure O 0
and O 0
link O 0
them O 0
to O 0
study O 0
participants O 0
' O 0
geocoded O 0
addresses O 0
. O 0

RESULTS O 0
: O 0
We O 0
observed O 0
positive O 0
associations O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
with O 0
ozone B-Chemical 0
( O 0
odds O 0
ratio O 0
= O 0
1 O 0
. O 0
39 O 0
; O 0
95 O 0
% O 0
CI O 0
: O 0
0 O 0
. O 0
98 O 0
to O 0
1 O 0
. O 0
98 O 0
) O 0
and O 0
fine O 0
particulate B-Chemical 0
matter I-Chemical 0
( O 0
odds O 0
ratio O 0
= O 0
1 O 0
. O 0
34 O 0
; O 0
95 O 0
% O 0
CI O 0
: O 0
0 O 0
. O 0
93 O 0
to O 0
1 O 0
. O 0
93 O 0
) O 0
in O 0
North O 0
Carolina O 0
but O 0
not O 0
in O 0
Iowa O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
plausibility O 0
of O 0
an O 0
effect O 0
of O 0
ambient O 0
concentrations O 0
of O 0
these O 0
pollutants O 0
on O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
risk O 0
is O 0
supported O 0
by O 0
experimental O 0
data O 0
demonstrating O 0
damage O 0
to O 0
dopaminergic O 0
neurons O 0
at O 0
relevant O 0
concentrations O 0
. O 0

Additional O 0
studies O 0
are O 0
needed O 0
to O 0
address O 0
uncertainties O 0
related O 0
to O 0
confounding O 0
and O 0
to O 0
examine O 0
temporal O 0
aspects O 0
of O 0
the O 0
associations O 0
we O 0
observed O 0
. O 0

Low O 0
functional O 0
programming O 0
of O 0
renal O 0
AT2R O 0
mediates O 0
the O 0
developmental O 0
origin O 0
of O 0
glomerulosclerosis B-Disease 0
in O 0
adult O 0
offspring O 0
induced O 0
by O 0
prenatal O 0
caffeine B-Chemical 0
exposure O 0
. O 0

UNASSIGNED O 0
: O 0
Our O 0
previous O 0
study O 0
has O 0
indicated O 0
that O 0
prenatal O 0
caffeine B-Chemical 0
exposure O 0
( O 0
PCE O 0
) O 0
could O 0
induce O 0
intrauterine B-Disease 0
growth I-Disease 0
retardation I-Disease 0
( O 0
IUGR B-Disease 0
) O 0
of O 0
offspring O 0
. O 0

Recent O 0
research O 0
suggested O 0
that O 0
IUGR B-Disease 0
is O 0
a O 0
risk O 0
factor O 0
for O 0
glomerulosclerosis B-Disease 0
. O 0

However O 0
, O 0
whether O 0
PCE O 0
could O 0
induce O 0
glomerulosclerosis B-Disease 0
and O 0
its O 0
underlying O 0
mechanisms O 0
remain O 0
unknown O 0
. O 0

This O 0
study O 0
aimed O 0
to O 0
demonstrate O 0
the O 0
induction O 0
to O 0
glomerulosclerosis B-Disease 0
in O 0
adult O 0
offspring O 0
by O 0
PCE O 0
and O 0
its O 0
intrauterine O 0
programming O 0
mechanisms O 0
. O 0

A O 0
rat O 0
model O 0
of O 0
IUGR B-Disease 0
was O 0
established O 0
by O 0
PCE O 0
, O 0
male O 0
fetuses O 0
and O 0
adult O 0
offspring O 0
at O 0
the O 0
age O 0
of O 0
postnatal O 0
week O 0
24 O 0
were O 0
euthanized O 0
. O 0

The O 0
results O 0
revealed O 0
that O 0
the O 0
adult O 0
offspring O 0
kidneys O 0
in O 0
the O 0
PCE O 0
group O 0
exhibited O 0
glomerulosclerosis B-Disease 0
as O 0
well O 0
as O 0
interstitial B-Disease 0
fibrosis I-Disease 0
, O 0
accompanied O 0
by O 0
elevated O 0
levels O 0
of O 0
serum O 0
creatinine B-Chemical 0
and O 0
urine O 0
protein O 0
. O 0

Renal O 0
angiotensin B-Chemical 0
II I-Chemical 0
receptor O 0
type O 0
2 O 0
( O 0
AT2R O 0
) O 0
gene O 0
expression O 0
in O 0
adult O 0
offspring O 0
was O 0
reduced O 0
by O 0
PCE O 0
, O 0
whereas O 0
the O 0
renal O 0
angiotensin B-Chemical 0
II I-Chemical 0
receptor O 0
type O 0
1a O 0
( O 0
AT1aR O 0
) O 0
/ O 0
AT2R O 0
expression O 0
ratio O 0
was O 0
increased O 0
. O 0

The O 0
fetal O 0
kidneys O 0
in O 0
the O 0
PCE O 0
group O 0
displayed O 0
an O 0
enlarged O 0
Bowman O 0
' O 0
s O 0
space O 0
and O 0
a O 0
shrunken O 0
glomerular O 0
tuft O 0
, O 0
accompanied O 0
by O 0
a O 0
reduced O 0
cortex O 0
width O 0
and O 0
an O 0
increase O 0
in O 0
the O 0
nephrogenic O 0
zone O 0
/ O 0
cortical O 0
zone O 0
ratio O 0
. O 0

Observation O 0
by O 0
electronic O 0
microscope O 0
revealed O 0
structural O 0
damage O 0
of O 0
podocytes O 0
; O 0
the O 0
reduced O 0
expression O 0
level O 0
of O 0
podocyte O 0
marker O 0
genes O 0
, O 0
nephrin O 0
and O 0
podocin O 0
, O 0
was O 0
also O 0
detected O 0
by O 0
q O 0
- O 0
PCR O 0
. O 0

Moreover O 0
, O 0
AT2R O 0
gene O 0
and O 0
protein O 0
expressions O 0
in O 0
fetal O 0
kidneys O 0
were O 0
inhibited O 0
by O 0
PCE O 0
, O 0
associated O 0
with O 0
the O 0
repression O 0
of O 0
the O 0
gene O 0
expression O 0
of O 0
glial O 0
- O 0
cell O 0
- O 0
line O 0
- O 0
derived O 0
neurotrophic O 0
factor O 0
( O 0
GDNF O 0
) O 0
/ O 0
tyrosine B-Chemical 0
kinase O 0
receptor O 0
( O 0
c O 0
- O 0
Ret O 0
) O 0
signaling O 0
pathway O 0
. O 0

These O 0
results O 0
demonstrated O 0
that O 0
PCE O 0
could O 0
induce O 0
dysplasia B-Disease 0
of I-Disease 0
fetal I-Disease 0
kidneys I-Disease 0
as O 0
well O 0
as O 0
glomerulosclerosis B-Disease 0
of O 0
adult O 0
offspring O 0
, O 0
and O 0
the O 0
low O 0
functional O 0
programming O 0
of O 0
renal O 0
AT2R O 0
might O 0
mediate O 0
the O 0
developmental O 0
origin O 0
of O 0
adult O 0
glomerulosclerosis B-Disease 0
. O 0

1 B-Chemical 0
, I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
Butadiene I-Chemical 0
, O 0
CML B-Disease 0
and O 0
the O 0
t O 0
( O 0
9 O 0
: O 0
22 O 0
) O 0
translocation O 0
: O 0
A O 0
reality O 0
check O 0
. O 0

UNASSIGNED O 0
: O 0
Epidemiological O 0
studies O 0
of O 0
1 B-Chemical 0
, I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
butadiene I-Chemical 0
have O 0
suggest O 0
that O 0
exposures O 0
to O 0
humans O 0
are O 0
associated O 0
with O 0
chronic B-Disease 0
myeloid I-Disease 0
leukemia I-Disease 0
( O 0
CML B-Disease 0
) O 0
. O 0

CML B-Disease 0
has O 0
a O 0
well O 0
- O 0
documented O 0
association O 0
with O 0
ionizing O 0
radiation O 0
, O 0
but O 0
reports O 0
of O 0
associations O 0
with O 0
chemical O 0
exposures O 0
have O 0
been O 0
questioned O 0
. O 0

Ionizing O 0
radiation O 0
is O 0
capable O 0
of O 0
inducing O 0
the O 0
requisite O 0
CML B-Disease 0
- O 0
associated O 0
t O 0
( O 0
9 O 0
: O 0
22 O 0
) O 0
translocation O 0
( O 0
Philadelphia B-Disease 0
chromosome I-Disease 0
) O 0
in O 0
appropriate O 0
cells O 0
in O 0
vitro O 0
but O 0
, O 0
thus O 0
far O 0
, O 0
chemicals O 0
have O 0
not O 0
shown O 0
this O 0
capacity O 0
. O 0

We O 0
have O 0
proposed O 0
that O 0
1 B-Chemical 0
, I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
butadiene I-Chemical 0
metabolites O 0
be O 0
so O 0
tested O 0
as O 0
a O 0
reality O 0
check O 0
on O 0
the O 0
epidemiological O 0
reports O 0
. O 0

In O 0
order O 0
to O 0
conduct O 0
reliable O 0
testing O 0
in O 0
this O 0
regard O 0
, O 0
it O 0
is O 0
essential O 0
that O 0
a O 0
positive O 0
control O 0
for O 0
induction O 0
be O 0
available O 0
. O 0

We O 0
have O 0
used O 0
ionizing O 0
radiation O 0
to O 0
develop O 0
such O 0
a O 0
control O 0
. O 0

Results O 0
described O 0
here O 0
demonstrate O 0
that O 0
this O 0
agent O 0
does O 0
in O 0
fact O 0
induce O 0
pathogenic O 0
t O 0
( O 0
9 O 0
: O 0
22 O 0
) O 0
translocations O 0
in O 0
a O 0
human O 0
myeloid O 0
cell O 0
line O 0
in O 0
vitro O 0
, O 0
but O 0
does O 0
so O 0
at O 0
low O 0
frequencies O 0
. O 0

Conditions O 0
that O 0
will O 0
be O 0
required O 0
for O 0
studies O 0
of O 0
1 B-Chemical 0
, I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
butadiene I-Chemical 0
are O 0
discussed O 0
. O 0

Cancer B-Disease 0
incidence O 0
and O 0
metolachlor B-Chemical 0
use O 0
in O 0
the O 0
Agricultural O 0
Health O 0
Study O 0
: O 0
An O 0
update O 0
. O 0

UNASSIGNED O 0
: O 0
Metolachlor B-Chemical 0
, O 0
a O 0
widely O 0
used O 0
herbicide O 0
, O 0
is O 0
classified O 0
as O 0
a O 0
Group O 0
C O 0
carcinogen O 0
by O 0
the O 0
U O 0
. O 0
S O 0
. O 0

Environmental O 0
Protection O 0
Agency O 0
based O 0
on O 0
increased O 0
liver B-Disease 0
neoplasms I-Disease 0
in O 0
female O 0
rats O 0
. O 0

Epidemiologic O 0
studies O 0
of O 0
the O 0
health O 0
effects O 0
of O 0
metolachlor B-Chemical 0
have O 0
been O 0
limited O 0
. O 0

The O 0
Agricultural O 0
Health O 0
Study O 0
( O 0
AHS O 0
) O 0
is O 0
a O 0
prospective O 0
cohort O 0
study O 0
including O 0
licensed O 0
private O 0
and O 0
commercial O 0
pesticide O 0
applicators O 0
in O 0
Iowa O 0
and O 0
North O 0
Carolina O 0
enrolled O 0
1993 O 0
- O 0
1997 O 0
. O 0

We O 0
evaluated O 0
cancer B-Disease 0
incidence O 0
through O 0
2010 O 0
/ O 0
2011 O 0
( O 0
NC O 0
/ O 0
IA O 0
) O 0
for O 0
49 O 0
, O 0
616 O 0
applicators O 0
, O 0
53 O 0
% O 0
of O 0
whom O 0
reported O 0
ever O 0
using O 0
metolachlor B-Chemical 0
. O 0

We O 0
used O 0
Poisson O 0
regression O 0
to O 0
evaluate O 0
relations O 0
between O 0
two O 0
metrics O 0
of O 0
metolachlor B-Chemical 0
use O 0
( O 0
lifetime O 0
days O 0
, O 0
intensity O 0
- O 0
weighted O 0
lifetime O 0
days O 0
) O 0
and O 0
cancer B-Disease 0
incidence O 0
. O 0

We O 0
saw O 0
no O 0
association O 0
between O 0
metolachlor B-Chemical 0
use O 0
and O 0
incidence O 0
of O 0
all O 0
cancers B-Disease 0
combined O 0
( O 0
n O 0
= O 0
5 O 0
, O 0
701 O 0
with O 0
a O 0
5 O 0
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year O 0
lag O 0
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most O 0
site O 0
- O 0
specific O 0
cancers B-Disease 0
. O 0

For O 0
liver B-Disease 0
cancer I-Disease 0
, O 0
in O 0
analyses O 0
restricted O 0
to O 0
exposed O 0
workers O 0
, O 0
elevations O 0
observed O 0
at O 0
higher O 0
categories O 0
of O 0
use O 0
were O 0
not O 0
statistically O 0
significant O 0
. O 0

However O 0
, O 0
trends O 0
for O 0
both O 0
lifetime O 0
and O 0
intensity O 0
- O 0
weighted O 0
lifetime O 0
days O 0
of O 0
metolachor B-Chemical 0
use O 0
were O 0
positive O 0
and O 0
statistically O 0
significant O 0
with O 0
an O 0
unexposed O 0
reference O 0
group O 0
. O 0

A O 0
similar O 0
pattern O 0
was O 0
observed O 0
for O 0
follicular B-Disease 0
cell I-Disease 0
lymphoma I-Disease 0
, O 0
but O 0
no O 0
other O 0
lymphoma B-Disease 0
subtypes O 0
. O 0

An O 0
earlier O 0
suggestion O 0
of O 0
increased O 0
lung B-Disease 0
cancer I-Disease 0
risk O 0
at O 0
high O 0
levels O 0
of O 0
metolachlor B-Chemical 0
use O 0
in O 0
this O 0
cohort O 0
was O 0
not O 0
confirmed O 0
in O 0
this O 0
update O 0
. O 0

This O 0
suggestion O 0
of O 0
an O 0
association O 0
between O 0
metolachlor B-Chemical 0
and O 0
liver B-Disease 0
cancer I-Disease 0
among O 0
pesticide O 0
applicators O 0
is O 0
a O 0
novel O 0
finding O 0
and O 0
echoes O 0
observation O 0
of O 0
increased O 0
liver B-Disease 0
neoplasms I-Disease 0
in O 0
some O 0
animal O 0
studies O 0
. O 0

However O 0
, O 0
our O 0
findings O 0
for O 0
both O 0
liver B-Disease 0
cancer I-Disease 0
and O 0
follicular O 0
cell O 0
lymphoma B-Disease 0
warrant O 0
follow O 0
- O 0
up O 0
to O 0
better O 0
differentiate O 0
effects O 0
of O 0
metolachlor B-Chemical 0
use O 0
from O 0
other O 0
factors O 0
. O 0

Mechanisms O 0
Underlying O 0
Latent O 0
Disease O 0
Risk O 0
Associated O 0
with O 0
Early O 0
- O 0
Life O 0
Arsenic B-Chemical 0
Exposure O 0
: O 0
Current O 0
Research O 0
Trends O 0
and O 0
Scientific O 0
Gaps O 0
. O 0

BACKGROUND O 0
: O 0
Millions O 0
of O 0
individuals O 0
worldwide O 0
, O 0
particularly O 0
those O 0
living O 0
in O 0
rural O 0
and O 0
developing O 0
areas O 0
, O 0
are O 0
exposed O 0
to O 0
harmful O 0
levels O 0
of O 0
inorganic B-Chemical 0
arsenic I-Chemical 0
( O 0
iAs B-Chemical 0
) O 0
in O 0
their O 0
drinking O 0
water O 0
. O 0

Inorganic B-Chemical 0
As I-Chemical 0
exposure O 0
during O 0
key O 0
developmental O 0
periods O 0
is O 0
associated O 0
with O 0
a O 0
variety O 0
of O 0
adverse O 0
health O 0
effects O 0
including O 0
those O 0
that O 0
are O 0
evident O 0
in O 0
adulthood O 0
. O 0

There O 0
is O 0
considerable O 0
interest O 0
in O 0
identifying O 0
the O 0
molecular O 0
mechanisms O 0
that O 0
relate O 0
early O 0
- O 0
life O 0
iAs B-Chemical 0
exposure O 0
to O 0
the O 0
development O 0
of O 0
these O 0
latent O 0
diseases O 0
, O 0
particularly O 0
in O 0
relationship O 0
to O 0
cancer B-Disease 0
. O 0

OBJECTIVES O 0
: O 0
This O 0
work O 0
summarizes O 0
research O 0
on O 0
the O 0
molecular O 0
mechanisms O 0
that O 0
underlie O 0
the O 0
increased O 0
risk O 0
of O 0
cancer B-Disease 0
development O 0
in O 0
adulthood O 0
that O 0
is O 0
associated O 0
with O 0
early O 0
- O 0
life O 0
iAs B-Chemical 0
exposure O 0
. O 0

DISCUSSION O 0
: O 0
Epigenetic O 0
reprogramming O 0
that O 0
imparts O 0
functional O 0
changes O 0
in O 0
gene O 0
expression O 0
, O 0
the O 0
development O 0
of O 0
cancer B-Disease 0
stem O 0
cells O 0
, O 0
and O 0
immunomodulation O 0
are O 0
plausible O 0
underlying O 0
mechanisms O 0
by O 0
which O 0
early O 0
- O 0
life O 0
iAs B-Chemical 0
exposure O 0
elicits O 0
latent O 0
carcinogenic O 0
effects O 0
. O 0

CONCLUSIONS O 0
: O 0
Evidence O 0
is O 0
mounting O 0
that O 0
relates O 0
early O 0
- O 0
life O 0
iAs B-Chemical 0
exposure O 0
and O 0
cancer B-Disease 0
development O 0
later O 0
in O 0
life O 0
. O 0

Future O 0
research O 0
should O 0
include O 0
animal O 0
studies O 0
that O 0
address O 0
mechanistic O 0
hypotheses O 0
and O 0
studies O 0
of O 0
human O 0
populations O 0
that O 0
integrate O 0
early O 0
- O 0
life O 0
exposure O 0
, O 0
molecular O 0
alterations O 0
, O 0
and O 0
latent O 0
disease O 0
outcomes O 0
. O 0

Nifedipine B-Chemical 0
induced O 0
bradycardia B-Disease 0
in O 0
a O 0
patient O 0
with O 0
autonomic B-Disease 0
neuropathy I-Disease 0
. O 0

An O 0
80 O 0
year O 0
old O 0
diabetic B-Disease 0
male O 0
with O 0
evidence O 0
of O 0
peripheral B-Disease 0
and I-Disease 0
autonomic I-Disease 0
neuropathy I-Disease 0
was O 0
admitted O 0
with O 0
chest B-Disease 0
pain I-Disease 0
. O 0

He O 0
was O 0
found O 0
to O 0
have O 0
atrial B-Disease 0
flutter I-Disease 0
at O 0
a O 0
ventricular O 0
rate O 0
of O 0
70 O 0
/ O 0
min O 0
which O 0
slowed O 0
down O 0
to O 0
30 O 0
- O 0
40 O 0
/ O 0
min O 0
when O 0
nifedipine B-Chemical 0
( O 0
60 O 0
mg O 0
) O 0
in O 0
3 O 0
divided O 0
doses O 0
, O 0
during O 0
which O 0
he O 0
was O 0
paced O 0
at O 0
a O 0
rate O 0
of O 0
70 O 0
/ O 0
min O 0
. O 0

This O 0
is O 0
inconsistent O 0
with O 0
the O 0
well O 0
- O 0
established O 0
finding O 0
that O 0
nifedipine B-Chemical 0
induces O 0
tachycardia B-Disease 0
in O 0
normally O 0
innervated O 0
hearts O 0
. O 0

However O 0
, O 0
in O 0
hearts O 0
deprived O 0
of O 0
compensatory O 0
sympathetic O 0
drive O 0
, O 0
it O 0
may O 0
lead O 0
to O 0
bradycardia B-Disease 0
. O 0

The O 0
effect O 0
of O 0
haloperidol B-Chemical 0
in O 0
cocaine B-Chemical 0
and O 0
amphetamine B-Chemical 0
intoxication O 0
. O 0

The O 0
effectiveness O 0
of O 0
haloperidol B-Chemical 0
pretreatment O 0
in O 0
preventing O 0
the O 0
toxic O 0
effects O 0
of O 0
high O 0
doses O 0
of O 0
amphetamine B-Chemical 0
and O 0
cocaine B-Chemical 0
was O 0
studied O 0
in O 0
rats O 0
. O 0

In O 0
this O 0
model O 0
, O 0
toxic O 0
effects O 0
were O 0
induced O 0
by O 0
intraperitoneal O 0
( O 0
i O 0
. O 0
p O 0
. O 0
) O 0
injection O 0
of O 0
amphetamine B-Chemical 0
75 O 0
mg O 0
/ O 0
kg O 0
( O 0
100 O 0
% O 0
death O 0
rate O 0
) O 0
or O 0
cocaine B-Chemical 0
70 O 0
mg O 0
/ O 0
kg O 0
( O 0
82 O 0
% O 0
death O 0
rate O 0
) O 0
. O 0

Haloperidol B-Chemical 0
failed O 0
to O 0
prevent O 0
amphetamine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
, O 0
but O 0
did O 0
lower O 0
the O 0
mortality O 0
rate O 0
at O 0
most O 0
doses O 0
tested O 0
. O 0

Haloperidol B-Chemical 0
decreased O 0
the O 0
incidence O 0
of O 0
cocaine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
at O 0
the O 0
two O 0
highest O 0
doses O 0
, O 0
but O 0
the O 0
lowering O 0
of O 0
the O 0
mortality O 0
rate O 0
did O 0
not O 0
reach O 0
statistical O 0
significance O 0
at O 0
any O 0
dose O 0
. O 0

These O 0
data O 0
suggest O 0
a O 0
protective O 0
role O 0
for O 0
the O 0
central O 0
dopamine B-Chemical 0
blocker O 0
haloperidol B-Chemical 0
against O 0
death O 0
from O 0
high O 0
- O 0
dose O 0
amphetamine B-Chemical 0
exposure O 0
without O 0
reducing O 0
the O 0
incidence O 0
of O 0
seizures B-Disease 0
. O 0

In O 0
contrast O 0
, O 0
haloperidol B-Chemical 0
demonstrated O 0
an O 0
ability O 0
to O 0
reduce O 0
cocaine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
without O 0
significantly O 0
reducing O 0
mortality O 0
. O 0

Autoradiographic O 0
evidence O 0
of O 0
estrogen B-Chemical 0
binding O 0
sites O 0
in O 0
nuclei O 0
of O 0
diethylstilbesterol B-Chemical 0
induced O 0
hamster O 0
renal B-Disease 0
carcinomas I-Disease 0
. O 0

Estrogen B-Chemical 0
binding O 0
sites O 0
were O 0
demonstrated O 0
by O 0
autoradiography O 0
in O 0
one O 0
transplantable O 0
and O 0
five O 0
primary O 0
diethylstilbesterol B-Chemical 0
induced O 0
renal B-Disease 0
carcinomas I-Disease 0
in O 0
three O 0
hamsters O 0
. O 0

Radiolabelling O 0
, O 0
following O 0
the O 0
in O 0
vivo O 0
injection O 0
of O 0
3H O 0
- O 0
17 O 0
beta O 0
estradiol B-Chemical 0
, O 0
was O 0
increased O 0
only O 0
over O 0
the O 0
nuclei O 0
of O 0
tumor B-Disease 0
cells O 0
; O 0
stereologic O 0
analysis O 0
revealed O 0
a O 0
4 O 0
. O 0
5 O 0
- O 0
to O 0
6 O 0
. O 0
7 O 0
- O 0
times O 0
higher O 0
concentration O 0
of O 0
reduced O 0
silver B-Chemical 0
grains O 0
over O 0
nuclei O 0
than O 0
cytoplasm O 0
of O 0
these O 0
cells O 0
. O 0

Despite O 0
rapid O 0
tubular O 0
excretion O 0
of O 0
estradiol B-Chemical 0
which O 0
peaked O 0
in O 0
less O 0
than O 0
1 O 0
h O 0
, O 0
the O 0
normal O 0
cells O 0
did O 0
not O 0
appear O 0
to O 0
bind O 0
the O 0
ligand O 0
. O 0

This O 0
is O 0
the O 0
first O 0
published O 0
report O 0
documenting O 0
the O 0
preferential O 0
in O 0
vivo O 0
binding O 0
of O 0
estrogen B-Chemical 0
to O 0
nuclei O 0
of O 0
cells O 0
in O 0
estrogen B-Chemical 0
induced O 0
hamster O 0
renal B-Disease 0
carcinomas I-Disease 0
. O 0

Bradycardia B-Disease 0
due O 0
to O 0
biperiden B-Chemical 0
. O 0

In O 0
a O 0
38 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
patient O 0
suffering O 0
from O 0
a O 0
severe O 0
postzosteric B-Disease 0
trigeminal B-Disease 0
neuralgia I-Disease 0
, O 0
intravenous O 0
application O 0
of O 0
10 O 0
mg O 0
biperiden B-Chemical 0
lactate I-Chemical 0
led O 0
to O 0
a O 0
long O 0
- O 0
lasting O 0
paradoxical O 0
reaction O 0
characterized O 0
by O 0
considerable O 0
bradycardia B-Disease 0
, O 0
dysarthria B-Disease 0
, O 0
and O 0
dysphagia B-Disease 0
. O 0

The O 0
heart O 0
rate O 0
was O 0
back O 0
to O 0
normal O 0
within O 0
12 O 0
hours O 0
upon O 0
administration O 0
of O 0
orciprenaline B-Chemical 0
under O 0
cardiac O 0
monitoring O 0
in O 0
an O 0
intensive O 0
care O 0
unit O 0
. O 0

Bradycardia B-Disease 0
induced O 0
by O 0
biperiden B-Chemical 0
is O 0
attributed O 0
to O 0
the O 0
speed O 0
of O 0
injection O 0
and O 0
to O 0
a O 0
dose O 0
- O 0
related O 0
dual O 0
effect O 0
of O 0
atropine B-Chemical 0
- O 0
like O 0
drugs O 0
on O 0
muscarine B-Chemical 0
receptors O 0
. O 0

Deliberate O 0
hypotension B-Disease 0
induced O 0
by O 0
labetalol B-Chemical 0
with O 0
halothane B-Chemical 0
, O 0
enflurane B-Chemical 0
or O 0
isoflurane B-Chemical 0
for O 0
middle O 0
- O 0
ear O 0
surgery O 0
. O 0

The O 0
feasibility O 0
of O 0
using O 0
labetalol B-Chemical 0
, O 0
an O 0
alpha O 0
- O 0
and O 0
beta O 0
- O 0
adrenergic O 0
blocking O 0
agent O 0
, O 0
as O 0
a O 0
hypotensive B-Disease 0
agent O 0
in O 0
combination O 0
with O 0
inhalation O 0
anaesthetics O 0
( O 0
halothane B-Chemical 0
, O 0
enflurane B-Chemical 0
or O 0
isoflurane B-Chemical 0
) O 0
was O 0
studied O 0
in O 0
23 O 0
adult O 0
patients O 0
undergoing O 0
middle O 0
- O 0
ear O 0
surgery O 0
. O 0

The O 0
mean O 0
arterial O 0
pressure O 0
was O 0
decreased O 0
from O 0
86 O 0
+ O 0
/ O 0
- O 0
5 O 0
( O 0
s O 0
. O 0
e O 0
. O 0
mean O 0
) O 0
mmHg O 0
to O 0
52 O 0
+ O 0
/ O 0
- O 0
1 O 0
mmHg O 0
( O 0
11 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
7 O 0
to O 0
6 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
kPa O 0
) O 0
for O 0
98 O 0
+ O 0
/ O 0
- O 0
10 O 0
min O 0
in O 0
the O 0
halothane B-Chemical 0
( O 0
H B-Chemical 0
) O 0
group O 0
, O 0
from O 0
79 O 0
+ O 0
/ O 0
- O 0
5 O 0
to O 0
53 O 0
+ O 0
/ O 0
- O 0
1 O 0
mmHg O 0
( O 0
10 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
7 O 0
to O 0
7 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
kPa O 0
) O 0
for O 0
129 O 0
+ O 0
/ O 0
- O 0
11 O 0
min O 0
in O 0
the O 0
enflurane B-Chemical 0
( O 0
E B-Chemical 0
) O 0
group O 0
, O 0
and O 0
from O 0
80 O 0
+ O 0
/ O 0
- O 0
4 O 0
to O 0
49 O 0
+ O 0
/ O 0
- O 0
1 O 0
mmHg O 0
( O 0
10 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
5 O 0
to O 0
6 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
kPa O 0
) O 0
for O 0
135 O 0
+ O 0
/ O 0
- O 0
15 O 0
min O 0
in O 0
the O 0
isoflurane B-Chemical 0
( O 0
I B-Chemical 0
) O 0
group O 0
. O 0

The O 0
mean O 0
H B-Chemical 0
concentration O 0
during O 0
hypotension B-Disease 0
in O 0
the O 0
inspiratory O 0
gas O 0
was O 0
0 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
vol O 0
% O 0
, O 0
the O 0
mean O 0
E B-Chemical 0
concentration O 0
1 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
vol O 0
% O 0
, O 0
and O 0
the O 0
mean O 0
I B-Chemical 0
concentration O 0
1 O 0
. O 0
0 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
vol O 0
% O 0
. O 0

In O 0
addition O 0
, O 0
the O 0
patients O 0
received O 0
fentanyl B-Chemical 0
and O 0
d B-Chemical 0
- I-Chemical 0
tubocurarine I-Chemical 0
. O 0

The O 0
initial O 0
dose O 0
of O 0
labetalol B-Chemical 0
for O 0
lowering O 0
blood O 0
pressure O 0
was O 0
similar O 0
, O 0
0 O 0
. O 0
52 O 0
- O 0
0 O 0
. O 0
59 O 0
mg O 0
/ O 0
kg O 0
, O 0
in O 0
all O 0
the O 0
groups O 0
. O 0

During O 0
hypotension B-Disease 0
, O 0
the O 0
heart O 0
rate O 0
was O 0
stable O 0
without O 0
tachy B-Disease 0
- I-Disease 0
or I-Disease 0
bradycardia I-Disease 0
. O 0

The O 0
operating O 0
conditions O 0
regarding O 0
bleeding B-Disease 0
were O 0
estimated O 0
in O 0
a O 0
double O 0
- O 0
blind O 0
manner O 0
, O 0
and O 0
did O 0
not O 0
differ O 0
significantly O 0
between O 0
the O 0
groups O 0
. O 0

During O 0
hypotension B-Disease 0
, O 0
the O 0
serum O 0
creatinine B-Chemical 0
concentration O 0
rose O 0
significantly O 0
in O 0
all O 0
groups O 0
from O 0
the O 0
values O 0
before O 0
hypotension B-Disease 0
and O 0
returned O 0
postoperatively O 0
to O 0
the O 0
initial O 0
level O 0
in O 0
the O 0
other O 0
groups O 0
, O 0
except O 0
the O 0
isoflurane B-Chemical 0
group O 0
. O 0

After O 0
hypotension B-Disease 0
there O 0
was O 0
no O 0
rebound O 0
phenomenon O 0
in O 0
either O 0
blood O 0
pressure O 0
or O 0
heart O 0
rate O 0
. O 0

These O 0
results O 0
indicate O 0
that O 0
labetalol B-Chemical 0
induces O 0
easily O 0
adjustable O 0
hypotension B-Disease 0
without O 0
compensatory O 0
tachycardia B-Disease 0
and O 0
rebound O 0
hypertension B-Disease 0
. O 0

Convulsion B-Disease 0
following O 0
intravenous O 0
fluorescein B-Chemical 0
angiography O 0
. O 0

Tonic B-Disease 0
- I-Disease 0
clonic I-Disease 0
seizures I-Disease 0
followed O 0
intravenous O 0
fluorescein B-Chemical 0
injection O 0
for O 0
fundus O 0
angiography O 0
in O 0
a O 0
47 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
. O 0

Despite O 0
precautions O 0
this O 0
adverse O 0
reaction O 0
recurred O 0
on O 0
re O 0
- O 0
exposure O 0
to O 0
intravenous O 0
fluorescein B-Chemical 0
. O 0

Pharmacology O 0
of O 0
ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
( O 0
phenytoin B-Chemical 0
prodrug O 0
) O 0
. O 0

ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
, O 0
the O 0
disodium B-Chemical 0
phosphate I-Chemical 0
ester I-Chemical 0
of O 0
3 B-Chemical 0
- I-Chemical 0
hydroxymethyl I-Chemical 0
- I-Chemical 0
5 I-Chemical 0
, I-Chemical 0
5 I-Chemical 0
- I-Chemical 0
diphenylhydantoin I-Chemical 0
, O 0
is O 0
a O 0
prodrug O 0
of O 0
phenytoin B-Chemical 0
with O 0
advantageous O 0
physicochemical O 0
properties O 0
. O 0

ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
is O 0
rapidly O 0
converted O 0
enzymatically O 0
to O 0
phenytoin B-Chemical 0
in O 0
vivo O 0
. O 0

ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
and O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
have O 0
equivalent O 0
anticonvulsant O 0
activity O 0
against O 0
seizures B-Disease 0
induced O 0
by O 0
maximal O 0
electroshock O 0
( O 0
MES O 0
) O 0
in O 0
mice O 0
following O 0
i O 0
. O 0
p O 0
. O 0
, O 0
oral O 0
, O 0
or O 0
i O 0
. O 0
v O 0
. O 0
administration O 0
. O 0

The O 0
ED50 O 0
doses O 0
were O 0
16 O 0
mg O 0
/ O 0
kg O 0
for O 0
i O 0
. O 0
v O 0
. O 0
ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
and O 0
8 O 0
mg O 0
/ O 0
kg O 0
for O 0
i O 0
. O 0
v O 0
. O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
. O 0

ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
and O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
have O 0
similar O 0
antiarrhythmic O 0
activity O 0
against O 0
ouabain B-Chemical 0
- O 0
induced O 0
ventricular B-Disease 0
tachycardia I-Disease 0
in O 0
anesthetized O 0
dogs O 0
. O 0

The O 0
total O 0
doses O 0
of O 0
ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
or O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
necessary O 0
to O 0
convert O 0
the O 0
arrhythmia B-Disease 0
to O 0
a O 0
normal O 0
sinus O 0
rhythm O 0
were O 0
24 O 0
+ O 0
/ O 0
- O 0
6 O 0
and O 0
14 O 0
+ O 0
/ O 0
- O 0
3 O 0
mg O 0
/ O 0
kg O 0
, O 0
respectively O 0
. O 0

Only O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
displayed O 0
in O 0
vitro O 0
antiarrhythmic O 0
activity O 0
against O 0
strophanthidin B-Chemical 0
- O 0
induced O 0
arrhythmias B-Disease 0
in O 0
guinea O 0
pig O 0
right O 0
atria O 0
. O 0

In O 0
anesthetized O 0
dogs O 0
, O 0
a O 0
high O 0
dose O 0
of O 0
ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
( O 0
31 O 0
mg O 0
/ O 0
kg O 0
) O 0
was O 0
infused O 0
over O 0
15 O 0
, O 0
20 O 0
, O 0
and O 0
30 O 0
min O 0
and O 0
the O 0
responses O 0
were O 0
compared O 0
to O 0
an O 0
equimolar O 0
dose O 0
of O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
( O 0
21 O 0
mg O 0
/ O 0
kg O 0
) O 0
. O 0

The O 0
ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
and O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
treatments O 0
produced O 0
similar O 0
marked O 0
reductions O 0
in O 0
diastolic O 0
blood O 0
pressure O 0
and O 0
contractile O 0
force O 0
( O 0
LVdP O 0
/ O 0
dt O 0
) O 0
. O 0

The O 0
maximum O 0
effects O 0
of O 0
each O 0
treatment O 0
occurred O 0
at O 0
the O 0
time O 0
of O 0
maximum O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
levels O 0
. O 0

Acute O 0
toxicity B-Disease 0
studies O 0
of O 0
ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
and O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
were O 0
carried O 0
out O 0
in O 0
mice O 0
, O 0
rats O 0
, O 0
rabbits O 0
, O 0
and O 0
dogs O 0
by O 0
i O 0
. O 0
v O 0
. O 0
, O 0
i O 0
. O 0
m O 0
. O 0
, O 0
and O 0
i O 0
. O 0
p O 0
. O 0
routes O 0
of O 0
administration O 0
. O 0

The O 0
systemic O 0
toxic O 0
signs O 0
of O 0
both O 0
agents O 0
were O 0
similar O 0
and O 0
occurred O 0
at O 0
approximately O 0
equivalent O 0
doses O 0
. O 0

Importantly O 0
, O 0
the O 0
local O 0
irritation O 0
of O 0
ACC B-Chemical 0
- I-Chemical 0
9653 I-Chemical 0
was O 0
markedly O 0
less O 0
than O 0
phenytoin B-Chemical 0
sodium I-Chemical 0
following O 0
i O 0
. O 0
m O 0
. O 0
administration O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Tachyphylaxis O 0
to O 0
systemic O 0
but O 0
not O 0
to O 0
airway O 0
responses O 0
during O 0
prolonged O 0
therapy O 0
with O 0
high O 0
dose O 0
inhaled O 0
salbutamol B-Chemical 0
in O 0
asthmatics B-Disease 0
. O 0

High O 0
doses O 0
of O 0
inhaled O 0
salbutamol B-Chemical 0
produce O 0
substantial O 0
improvements O 0
in O 0
airway O 0
response O 0
in O 0
patients O 0
with O 0
asthma B-Disease 0
, O 0
and O 0
are O 0
associated O 0
with O 0
dose O 0
- O 0
dependent O 0
systemic O 0
beta O 0
- O 0
adrenoceptor O 0
responses O 0
. O 0

The O 0
purpose O 0
of O 0
the O 0
present O 0
study O 0
was O 0
to O 0
investigate O 0
whether O 0
tachyphylaxis O 0
occurs O 0
during O 0
prolonged O 0
treatment O 0
with O 0
high O 0
dose O 0
inhaled O 0
salbutamol B-Chemical 0
. O 0

Twelve O 0
asthmatic B-Disease 0
patients O 0
( O 0
FEV1 O 0
, O 0
81 O 0
+ O 0
/ O 0
- O 0
4 O 0
% O 0
predicted O 0
) O 0
, O 0
requiring O 0
only O 0
occasional O 0
inhaled O 0
beta O 0
- O 0
agonists O 0
as O 0
their O 0
sole O 0
therapy O 0
, O 0
were O 0
given O 0
a O 0
14 O 0
- O 0
day O 0
treatment O 0
with O 0
high O 0
dose O 0
inhaled O 0
salbutamol B-Chemical 0
( O 0
HDS O 0
) O 0
, O 0
4 O 0
, O 0
000 O 0
micrograms O 0
daily O 0
, O 0
low O 0
dose O 0
inhaled O 0
salbutamol B-Chemical 0
( O 0
LDS O 0
) O 0
, O 0
800 O 0
micrograms O 0
daily O 0
, O 0
or O 0
placebo O 0
( O 0
PI O 0
) O 0
by O 0
metered O 0
- O 0
dose O 0
inhaler O 0
in O 0
a O 0
double O 0
- O 0
blind O 0
, O 0
randomized O 0
crossover O 0
design O 0
. O 0

During O 0
the O 0
14 O 0
- O 0
day O 0
run O 0
- O 0
in O 0
and O 0
during O 0
washout O 0
periods O 0
, O 0
inhaled O 0
beta O 0
- O 0
agonists O 0
were O 0
withheld O 0
and O 0
ipratropium B-Chemical 0
bromide I-Chemical 0
was O 0
substituted O 0
for O 0
rescue O 0
purposes O 0
. O 0

At O 0
the O 0
end O 0
of O 0
each O 0
14 O 0
- O 0
day O 0
treatment O 0
, O 0
a O 0
dose O 0
- O 0
response O 0
curve O 0
( O 0
DRC O 0
) O 0
was O 0
performed O 0
, O 0
and O 0
airway O 0
( O 0
FEV1 O 0
, O 0
FEF25 O 0
- O 0
75 O 0
) O 0
chronotropic O 0
( O 0
HR O 0
) O 0
, O 0
tremor B-Disease 0
, O 0
and O 0
metabolic O 0
( O 0
K B-Chemical 0
, O 0
Glu B-Chemical 0
) O 0
responses O 0
were O 0
measured O 0
at O 0
each O 0
step O 0
( O 0
from O 0
100 O 0
to O 0
4 O 0
, O 0
000 O 0
micrograms O 0
) O 0
. O 0

Treatment O 0
had O 0
no O 0
significant O 0
effect O 0
on O 0
baseline O 0
values O 0
. O 0

There O 0
were O 0
dose O 0
- O 0
dependent O 0
increases O 0
in O 0
FEV1 O 0
and O 0
FEF25 O 0
- O 0
75 O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
and O 0
pretreatment O 0
with O 0
HDS O 0
did O 0
not O 0
displace O 0
the O 0
DRC O 0
to O 0
the O 0
right O 0
. O 0

DRC O 0
for O 0
HR O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
K B-Chemical 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
and O 0
Glu B-Chemical 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
005 O 0
) O 0
were O 0
attenuated O 0
after O 0
treatment O 0
with O 0
HDS O 0
compared O 0
with O 0
PI O 0
. O 0

There O 0
were O 0
also O 0
differences O 0
between O 0
HDS O 0
and O 0
LDS O 0
for O 0
HR O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
and O 0
Glu B-Chemical 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
responses O 0
. O 0

Frequency O 0
and O 0
severity O 0
of O 0
subjective O 0
adverse O 0
effects O 0
were O 0
also O 0
reduced O 0
after O 0
HDS O 0
: O 0
tremor B-Disease 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
palpitations B-Disease 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Phenytoin B-Chemical 0
induced O 0
fatal O 0
hepatic B-Disease 0
injury I-Disease 0
. O 0

A O 0
61 O 0
year O 0
old O 0
female O 0
developed O 0
fatal O 0
hepatic B-Disease 0
failure I-Disease 0
after O 0
phenytoin B-Chemical 0
administration O 0
. O 0

A O 0
typical O 0
multisystem O 0
clinical O 0
pattern O 0
precedes O 0
the O 0
manifestations O 0
of O 0
hepatic B-Disease 0
injury I-Disease 0
. O 0

The O 0
hematologic O 0
, O 0
biochemical O 0
and O 0
pathologic O 0
features O 0
indicate O 0
a O 0
mixed O 0
hepatocellular B-Disease 0
damage I-Disease 0
due O 0
to O 0
drug B-Disease 0
hypersensitivity I-Disease 0
. O 0

In O 0
a O 0
patient O 0
receiving O 0
phenytoin B-Chemical 0
who O 0
presents O 0
a O 0
viral O 0
- O 0
like O 0
illness O 0
, O 0
early O 0
recognition O 0
and O 0
discontinuation O 0
of O 0
the O 0
drug O 0
are O 0
mandatory O 0
. O 0

Treatment O 0
of O 0
lethal O 0
pertussis B-Chemical 0
vaccine I-Chemical 0
reaction O 0
with O 0
histamine B-Chemical 0
H1 O 0
antagonists O 0
. O 0

We O 0
studied O 0
mortality O 0
after O 0
pertussis B-Disease 0
immunization O 0
in O 0
the O 0
mouse O 0
. O 0

Without O 0
treatment O 0
, O 0
73 O 0
of O 0
92 O 0
animals O 0
( O 0
80 O 0
% O 0
) O 0
died O 0
after O 0
injection O 0
of O 0
bovine O 0
serum O 0
albumin O 0
( O 0
BSA O 0
) O 0
on O 0
day O 0
+ O 0
7 O 0
of O 0
pertussis B-Disease 0
immunization O 0
. O 0

After O 0
pretreatment O 0
with O 0
3 O 0
mg O 0
of O 0
cyproheptadine B-Chemical 0
, O 0
2 O 0
mg O 0
mianserin B-Chemical 0
, O 0
or O 0
2 O 0
mg O 0
chlorpheniramine B-Chemical 0
, O 0
only O 0
5 O 0
of O 0
105 O 0
animals O 0
( O 0
5 O 0
% O 0
) O 0
died O 0
after O 0
receiving O 0
BSA O 0
on O 0
day O 0
+ O 0
7 O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Blockade O 0
of O 0
histamine B-Chemical 0
H1 O 0
receptors O 0
may O 0
reduce O 0
mortality O 0
in O 0
pertussis B-Disease 0
immunization O 0
- O 0
induced O 0
encephalopathy B-Disease 0
in O 0
mice O 0
. O 0

Support O 0
for O 0
adrenaline B-Chemical 0
- O 0
hypertension B-Disease 0
hypothesis O 0
: O 0
18 O 0
hour O 0
pressor O 0
effect O 0
after O 0
6 O 0
hours O 0
adrenaline B-Chemical 0
infusion O 0
. O 0

In O 0
a O 0
double O 0
blind O 0
, O 0
crossover O 0
study O 0
6 O 0
h O 0
infusions O 0
of O 0
adrenaline B-Chemical 0
( O 0
15 O 0
ng O 0
/ O 0
kg O 0
/ O 0
min O 0
; O 0
1 O 0
ng O 0
= O 0
5 O 0
. O 0
458 O 0
pmol O 0
) O 0
, O 0
noradrenaline B-Chemical 0
( O 0
30 O 0
ng O 0
/ O 0
kg O 0
/ O 0
min O 0
; O 0
1 O 0
ng O 0
= O 0
5 O 0
. O 0
911 O 0
pmol O 0
) O 0
, O 0
and O 0
a O 0
5 O 0
% O 0
dextrose B-Chemical 0
solution O 0
( O 0
5 O 0
. O 0
4 O 0
ml O 0
/ O 0
h O 0
) O 0
, O 0
were O 0
given O 0
to O 0
ten O 0
healthy O 0
volunteers O 0
in O 0
random O 0
order O 0
2 O 0
weeks O 0
apart O 0
. O 0

By O 0
means O 0
of O 0
intra O 0
- O 0
arterial O 0
ambulatory O 0
monitoring O 0
the O 0
haemodynamic O 0
effects O 0
were O 0
followed O 0
for O 0
18 O 0
h O 0
after O 0
the O 0
infusions O 0
were O 0
stopped O 0
. O 0

Adrenaline B-Chemical 0
, O 0
but O 0
not O 0
noradrenaline B-Chemical 0
, O 0
caused O 0
a O 0
delayed O 0
and O 0
protracted O 0
pressor O 0
effect O 0
. O 0

Over O 0
the O 0
total O 0
postinfusion O 0
period O 0
systolic O 0
and O 0
diastolic O 0
arterial O 0
pressure O 0
were O 0
6 O 0
( O 0
SEM O 0
2 O 0
) O 0
% O 0
and O 0
7 O 0
( O 0
2 O 0
) O 0
% O 0
, O 0
respectively O 0
, O 0
higher O 0
than O 0
after O 0
dextrose B-Chemical 0
infusion O 0
( O 0
ANOVA O 0
, O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Thus O 0
, O 0
" O 0
stress O 0
" O 0
levels O 0
of O 0
adrenaline B-Chemical 0
( O 0
230 O 0
pg O 0
/ O 0
ml O 0
) O 0
for O 0
6 O 0
h O 0
cause O 0
a O 0
delayed O 0
and O 0
protracted O 0
pressor O 0
effect O 0
. O 0

These O 0
findings O 0
are O 0
strong O 0
support O 0
for O 0
the O 0
adrenaline B-Chemical 0
- O 0
hypertension B-Disease 0
hypothesis O 0
in O 0
man O 0
. O 0

Effect O 0
of O 0
alkylxanthines B-Chemical 0
on O 0
gentamicin B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
in O 0
the O 0
rat O 0
. O 0

Adenosine B-Chemical 0
antagonists O 0
have O 0
been O 0
previously O 0
shown O 0
to O 0
be O 0
of O 0
benefit O 0
in O 0
some O 0
ischaemic B-Disease 0
and O 0
nephrotoxic B-Disease 0
models O 0
of O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
( O 0
ARF B-Disease 0
) O 0
. O 0

In O 0
the O 0
present O 0
study O 0
, O 0
the O 0
effects O 0
of O 0
three O 0
alkylxanthines B-Chemical 0
with O 0
different O 0
potencies O 0
as O 0
adenosine B-Chemical 0
antagonists O 0
8 B-Chemical 0
- I-Chemical 0
phenyltheophylline I-Chemical 0
, O 0
theophylline B-Chemical 0
and O 0
enprofylline B-Chemical 0
, O 0
were O 0
examined O 0
in O 0
rats O 0
developing O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
after O 0
4 O 0
daily O 0
injections O 0
of O 0
gentamicin B-Chemical 0
( O 0
200 O 0
mg O 0
kg O 0
- O 0
1 O 0
) O 0
. O 0

Renal O 0
function O 0
was O 0
assessed O 0
by O 0
biochemical O 0
( O 0
plasma O 0
urea B-Chemical 0
and O 0
creatinine B-Chemical 0
) O 0
, O 0
functional O 0
( O 0
urine O 0
analysis O 0
and O 0
[ O 0
3H O 0
] O 0
inulin O 0
and O 0
[ O 0
14C O 0
] O 0
p B-Chemical 0
- I-Chemical 0
aminohippuric I-Chemical 0
acid I-Chemical 0
clearances O 0
) O 0
and O 0
morphological O 0
( O 0
degree O 0
of O 0
necrosis B-Disease 0
) O 0
indices O 0
. O 0

The O 0
various O 0
drug O 0
treatments O 0
produced O 0
improvements O 0
in O 0
some O 0
, O 0
but O 0
not O 0
all O 0
, O 0
measurements O 0
of O 0
renal O 0
function O 0
. O 0

However O 0
, O 0
any O 0
improvement O 0
produced O 0
by O 0
drug O 0
treatment O 0
was O 0
largely O 0
a O 0
result O 0
of O 0
a O 0
beneficial O 0
effect O 0
exerted O 0
by O 0
its O 0
vehicle O 0
( O 0
polyethylene B-Chemical 0
glycol I-Chemical 0
and O 0
NaOH B-Chemical 0
) O 0
. O 0

The O 0
lack O 0
of O 0
any O 0
consistent O 0
protective O 0
effect O 0
noted O 0
with O 0
the O 0
alkylxanthines B-Chemical 0
tested O 0
in O 0
the O 0
present O 0
study O 0
indicates O 0
that O 0
adenosine B-Chemical 0
plays O 0
little O 0
, O 0
if O 0
any O 0
, O 0
pathophysiological O 0
role O 0
in O 0
gentamicin B-Chemical 0
- O 0
induced O 0
ARF B-Disease 0
. O 0

Adverse O 0
ocular O 0
reactions O 0
possibly O 0
associated O 0
with O 0
isotretinoin B-Chemical 0
. O 0

A O 0
total O 0
of O 0
261 O 0
adverse O 0
ocular O 0
reactions O 0
occurred O 0
in O 0
237 O 0
patients O 0
who O 0
received O 0
isotretinoin B-Chemical 0
, O 0
a O 0
commonly O 0
used O 0
drug O 0
in O 0
the O 0
treatment O 0
of O 0
severe O 0
cystic O 0
acne B-Disease 0
. O 0

Blepharoconjunctivitis B-Disease 0
, O 0
subjective O 0
complaints O 0
of O 0
dry B-Disease 0
eyes I-Disease 0
, O 0
blurred B-Disease 0
vision I-Disease 0
, O 0
contact O 0
lens O 0
intolerance O 0
, O 0
and O 0
photodermatitis B-Disease 0
are O 0
reversible O 0
side O 0
effects O 0
. O 0

More O 0
serious O 0
ocular O 0
adverse O 0
reactions O 0
include O 0
papilledema B-Disease 0
, O 0
pseudotumor B-Disease 0
cerebri I-Disease 0
, O 0
and O 0
white O 0
or O 0
gray O 0
subepithelial O 0
corneal B-Disease 0
opacities I-Disease 0
; O 0
all O 0
of O 0
these O 0
are O 0
reversible O 0
if O 0
the O 0
drug O 0
is O 0
discontinued O 0
. O 0

Reported O 0
cases O 0
of O 0
decreased O 0
dark O 0
adaptation O 0
are O 0
under O 0
investigation O 0
. O 0

Isotretinoin B-Chemical 0
is O 0
contraindicated O 0
in O 0
pregnancy O 0
because O 0
of O 0
the O 0
many O 0
reported O 0
congenital B-Disease 0
abnormalities I-Disease 0
after O 0
maternal O 0
use O 0
( O 0
including O 0
microphthalmos B-Disease 0
, O 0
orbital O 0
hypertelorism B-Disease 0
, O 0
and O 0
optic B-Disease 0
nerve I-Disease 0
hypoplasia I-Disease 0
) O 0
. O 0

Procaterol B-Chemical 0
and O 0
terbutaline B-Chemical 0
in O 0
bronchial B-Disease 0
asthma I-Disease 0
. O 0

A O 0
double O 0
- O 0
blind O 0
, O 0
placebo O 0
- O 0
controlled O 0
, O 0
cross O 0
- O 0
over O 0
study O 0
. O 0

Procaterol B-Chemical 0
, O 0
a O 0
new O 0
beta O 0
- O 0
2 O 0
adrenoceptor O 0
stimulant O 0
, O 0
was O 0
studied O 0
in O 0
a O 0
double O 0
- O 0
blind O 0
, O 0
placebo O 0
- O 0
controlled O 0
, O 0
cross O 0
- O 0
over O 0
trial O 0
in O 0
patients O 0
with O 0
bronchial B-Disease 0
asthma I-Disease 0
. O 0

Oral O 0
procaterol B-Chemical 0
50 O 0
micrograms O 0
b O 0
. O 0
d O 0
. O 0
, O 0
procaterol B-Chemical 0
100 O 0
micrograms O 0
b O 0
. O 0
d O 0
. O 0
, O 0
and O 0
terbutaline B-Chemical 0
5 O 0
mg O 0
t O 0
. O 0
i O 0
. O 0
d O 0
. O 0
, O 0
were O 0
compared O 0
when O 0
given O 0
randomly O 0
in O 0
1 O 0
- O 0
week O 0
treatment O 0
periods O 0
. O 0

The O 0
best O 0
clinical O 0
effect O 0
was O 0
found O 0
with O 0
terbutaline B-Chemical 0
. O 0

Both O 0
anti O 0
- O 0
asthmatic B-Disease 0
and O 0
tremorgenic B-Disease 0
effects O 0
of O 0
procaterol B-Chemical 0
were O 0
dose O 0
- O 0
related O 0
. O 0

Procaterol B-Chemical 0
appeared O 0
effective O 0
in O 0
the O 0
doses O 0
tested O 0
, O 0
and O 0
a O 0
twice O 0
daily O 0
regimen O 0
would O 0
appear O 0
to O 0
be O 0
suitable O 0
with O 0
this O 0
drug O 0
. O 0

Subacute O 0
effects O 0
of O 0
propranolol B-Chemical 0
and O 0
B O 0
24 O 0
/ O 0
76 O 0
on O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
rat O 0
heart B-Disease 0
hypertrophy I-Disease 0
in O 0
correlation O 0
with O 0
blood O 0
pressure O 0
. O 0

We O 0
compared O 0
the O 0
potential O 0
beta O 0
- O 0
receptor O 0
blocker O 0
, O 0
B O 0
24 O 0
/ O 0
76 O 0
i O 0
. O 0
e O 0
. O 0
1 O 0
- O 0
( O 0
2 O 0
, O 0
4 O 0
- O 0
dichlorophenoxy O 0
) O 0
- O 0
3 O 0
[ O 0
2 O 0
- O 0
3 O 0
, O 0
4 O 0
- O 0
dimethoxyphenyl O 0
) O 0
ethanolamino O 0
] O 0
- O 0
prop O 0
an O 0
- O 0
2 O 0
- O 0
ol O 0
, O 0
which O 0
is O 0
characterized O 0
by O 0
beta O 0
1 O 0
- O 0
adrenoceptor O 0
blocking O 0
and O 0
beta O 0
2 O 0
- O 0
adrenoceptor O 0
stimulating O 0
properties O 0
with O 0
propranolol B-Chemical 0
. O 0

The O 0
studies O 0
were O 0
performed O 0
using O 0
an O 0
experimental O 0
model O 0
of O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
heart B-Disease 0
hypertrophy I-Disease 0
in O 0
rats O 0
. O 0

A O 0
correlation O 0
of O 0
the O 0
blood O 0
pressure O 0
was O 0
neither O 0
found O 0
in O 0
the O 0
development O 0
nor O 0
in O 0
the O 0
attempt O 0
to O 0
suppress O 0
the O 0
development O 0
of O 0
heart B-Disease 0
hypertrophy I-Disease 0
with O 0
the O 0
two O 0
beta O 0
- O 0
receptor O 0
blockers O 0
. O 0

Both O 0
beta O 0
- O 0
blockers O 0
influenced O 0
the O 0
development O 0
of O 0
hypertrophy B-Disease 0
to O 0
a O 0
different O 0
, O 0
but O 0
not O 0
reproducible O 0
extent O 0
. O 0

It O 0
was O 0
possible O 0
to O 0
suppress O 0
the O 0
increased O 0
ornithine B-Chemical 0
decarboxylase O 0
activity O 0
with O 0
both O 0
beta O 0
- O 0
blockers O 0
in O 0
hypertrophied B-Disease 0
hearts I-Disease 0
, O 0
but O 0
there O 0
was O 0
no O 0
effect O 0
on O 0
the O 0
heart O 0
mass O 0
. O 0

Neither O 0
propranolol B-Chemical 0
nor O 0
B O 0
24 O 0
/ O 0
76 O 0
could O 0
stop O 0
the O 0
changes O 0
in O 0
the O 0
characteristic O 0
myosin O 0
isoenzyme O 0
pattern O 0
of O 0
the O 0
hypertrophied B-Disease 0
rat O 0
heart O 0
. O 0

Thus O 0
, O 0
the O 0
investigations O 0
did O 0
not O 0
provide O 0
any O 0
evidence O 0
that O 0
the O 0
beta O 0
- O 0
receptor O 0
blockers O 0
propranolol B-Chemical 0
and O 0
B O 0
24 O 0
/ O 0
76 O 0
have O 0
the O 0
potency O 0
to O 0
prevent O 0
isoproterenol B-Chemical 0
from O 0
producing O 0
heart B-Disease 0
hypertrophy I-Disease 0
. O 0

Increased O 0
anxiogenic O 0
effects O 0
of O 0
caffeine B-Chemical 0
in O 0
panic B-Disease 0
disorders I-Disease 0
. O 0

The O 0
effects O 0
of O 0
oral O 0
administration O 0
of O 0
caffeine B-Chemical 0
( O 0
10 O 0
mg O 0
/ O 0
kg O 0
) O 0
on O 0
behavioral O 0
ratings O 0
, O 0
somatic O 0
symptoms O 0
, O 0
blood O 0
pressure O 0
and O 0
plasma O 0
levels O 0
of O 0
3 B-Chemical 0
- I-Chemical 0
methoxy I-Chemical 0
- I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
hydroxyphenethyleneglycol I-Chemical 0
( O 0
MHPG B-Chemical 0
) O 0
and O 0
cortisol B-Chemical 0
were O 0
determined O 0
in O 0
17 O 0
healthy O 0
subjects O 0
and O 0
21 O 0
patients O 0
meeting O 0
DSM O 0
- O 0
III O 0
criteria O 0
for O 0
agoraphobia B-Disease 0
with O 0
panic B-Disease 0
attacks I-Disease 0
or O 0
panic B-Disease 0
disorder I-Disease 0
. O 0

Caffeine B-Chemical 0
produced O 0
significantly O 0
greater O 0
increases O 0
in O 0
subject O 0
- O 0
rated O 0
anxiety B-Disease 0
, O 0
nervousness O 0
, O 0
fear O 0
, O 0
nausea B-Disease 0
, O 0
palpitations B-Disease 0
, O 0
restlessness B-Disease 0
, O 0
and O 0
tremors B-Disease 0
in O 0
the O 0
patients O 0
compared O 0
with O 0
healthy O 0
subjects O 0
. O 0

In O 0
the O 0
patients O 0
, O 0
but O 0
not O 0
the O 0
healthy O 0
subjects O 0
, O 0
these O 0
symptoms O 0
were O 0
significantly O 0
correlated O 0
with O 0
plasma O 0
caffeine B-Chemical 0
levels O 0
. O 0

Seventy O 0
- O 0
one O 0
percent O 0
of O 0
the O 0
patients O 0
reported O 0
that O 0
the O 0
behavioral O 0
effects O 0
of O 0
caffeine B-Chemical 0
were O 0
similar O 0
to O 0
those O 0
experienced O 0
during O 0
panic B-Disease 0
attacks I-Disease 0
. O 0

Caffeine B-Chemical 0
did O 0
not O 0
alter O 0
plasma O 0
MHPG B-Chemical 0
levels O 0
in O 0
either O 0
the O 0
healthy O 0
subjects O 0
or O 0
patients O 0
. O 0

Caffeine B-Chemical 0
increased O 0
plasma O 0
cortisol B-Chemical 0
levels O 0
equally O 0
in O 0
the O 0
patient O 0
and O 0
healthy O 0
groups O 0
. O 0

Because O 0
caffeine B-Chemical 0
is O 0
an O 0
adenosine B-Chemical 0
receptor O 0
antagonist O 0
, O 0
these O 0
results O 0
suggest O 0
that O 0
some O 0
panic B-Disease 0
disorder I-Disease 0
patients O 0
may O 0
have O 0
abnormalities B-Disease 0
in I-Disease 0
neuronal I-Disease 0
systems I-Disease 0
involving O 0
adenosine B-Chemical 0
. O 0

Patients O 0
with O 0
anxiety B-Disease 0
disorders I-Disease 0
may O 0
benefit O 0
by O 0
avoiding O 0
caffeine B-Chemical 0
- O 0
containing O 0
foods O 0
and O 0
beverages O 0
. O 0

Comparison O 0
of O 0
the O 0
effect O 0
of O 0
oxitropium B-Chemical 0
bromide I-Chemical 0
and O 0
of O 0
slow O 0
- O 0
release O 0
theophylline B-Chemical 0
on O 0
nocturnal O 0
asthma B-Disease 0
. O 0

The O 0
effects O 0
of O 0
a O 0
new O 0
inhaled O 0
antimuscarinic O 0
drug O 0
, O 0
oxitropium B-Chemical 0
bromide I-Chemical 0
, O 0
and O 0
of O 0
a O 0
slow O 0
- O 0
release O 0
theophylline B-Chemical 0
preparation O 0
upon O 0
nocturnal O 0
asthma B-Disease 0
were O 0
compared O 0
in O 0
a O 0
placebo O 0
- O 0
controlled O 0
double O 0
- O 0
blind O 0
study O 0
. O 0

Two O 0
samples O 0
were O 0
studied O 0
: O 0
12 O 0
patients O 0
received O 0
oxitropium B-Chemical 0
at O 0
600 O 0
micrograms O 0
( O 0
6 O 0
subjects O 0
) O 0
or O 0
at O 0
400 O 0
micrograms O 0
t O 0
. O 0
i O 0
. O 0
d O 0
. O 0

( O 0
6 O 0
subjects O 0
) O 0
whereas O 0
11 O 0
received O 0
theophylline B-Chemical 0
at O 0
300 O 0
mg O 0
b O 0
. O 0
i O 0
. O 0
d O 0
. O 0

Morning O 0
dipping O 0
, O 0
assessed O 0
by O 0
the O 0
fall O 0
in O 0
peak O 0
flow O 0
overnight O 0
, O 0
was O 0
significantly O 0
reduced O 0
in O 0
the O 0
periods O 0
when O 0
either O 0
active O 0
drug O 0
was O 0
taken O 0
, O 0
whereas O 0
no O 0
difference O 0
was O 0
noticed O 0
during O 0
the O 0
placebo O 0
administration O 0
. O 0

No O 0
significant O 0
difference O 0
was O 0
noticed O 0
between O 0
results O 0
obtained O 0
with O 0
either O 0
active O 0
drug O 0
, O 0
as O 0
well O 0
as O 0
with O 0
either O 0
dosage O 0
of O 0
oxitropium B-Chemical 0
. O 0

No O 0
subject O 0
reported O 0
side O 0
effects O 0
of O 0
oxitropium B-Chemical 0
, O 0
as O 0
compared O 0
to O 0
three O 0
subjects O 0
reporting O 0
nausea B-Disease 0
, O 0
vomiting B-Disease 0
and O 0
tremors B-Disease 0
after O 0
theophylline B-Chemical 0
. O 0

Oxitropium B-Chemical 0
proves O 0
to O 0
be O 0
a O 0
valuable O 0
alternative O 0
to O 0
theophylline B-Chemical 0
in O 0
nocturnal O 0
asthma B-Disease 0
, O 0
since O 0
it O 0
is O 0
equally O 0
potent O 0
, O 0
safer O 0
and O 0
does O 0
not O 0
require O 0
the O 0
titration O 0
of O 0
dosage O 0
. O 0

Penicillin B-Chemical 0
anaphylaxis B-Disease 0
. O 0

A O 0
case O 0
of O 0
oral O 0
penicillin B-Chemical 0
anaphylaxis B-Disease 0
is O 0
described O 0
, O 0
and O 0
the O 0
terminology O 0
, O 0
occurrence O 0
, O 0
clinical O 0
manifestations O 0
, O 0
pathogenesis O 0
, O 0
prevention O 0
, O 0
and O 0
treatment O 0
of O 0
anaphylaxis B-Disease 0
are O 0
reviewed O 0
. O 0

Emergency O 0
physicians O 0
should O 0
be O 0
aware O 0
of O 0
oral O 0
penicillin B-Chemical 0
anaphylaxis B-Disease 0
in O 0
order O 0
to O 0
prevent O 0
its O 0
occurrence O 0
by O 0
prescribing O 0
the O 0
antibiotic O 0
judiciously O 0
and O 0
knowledgeably O 0
and O 0
to O 0
offer O 0
optimal O 0
medical O 0
therapy O 0
once O 0
this O 0
life O 0
- O 0
threatening O 0
reaction O 0
has O 0
begun O 0
. O 0

Reversible O 0
valproic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
dementia B-Disease 0
: O 0
a O 0
case O 0
report O 0
. O 0

Reversible O 0
valproic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
dementia B-Disease 0
was O 0
documented O 0
in O 0
a O 0
21 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
epilepsy B-Disease 0
who O 0
had O 0
a O 0
3 O 0
- O 0
year O 0
history O 0
of O 0
insidious O 0
progressive O 0
decline O 0
in O 0
global O 0
cognitive O 0
abilities O 0
documented O 0
by O 0
serial O 0
neuropsychological O 0
studies O 0
. O 0

Repeat O 0
neuropsychological O 0
testing O 0
7 O 0
weeks O 0
after O 0
discontinuation O 0
of O 0
the O 0
drug O 0
revealed O 0
dramatic O 0
improvement O 0
in O 0
IQ O 0
, O 0
memory O 0
, O 0
naming O 0
, O 0
and O 0
other O 0
tasks O 0
commensurate O 0
with O 0
clinical O 0
recovery O 0
in O 0
his O 0
intellectual O 0
capacity O 0
. O 0

Possible O 0
pathophysiological O 0
mechanisms O 0
which O 0
may O 0
have O 0
been O 0
operative O 0
in O 0
this O 0
case O 0
include O 0
: O 0
a O 0
direct O 0
central O 0
nervous O 0
system O 0
( O 0
CNS O 0
) O 0
toxic O 0
effect O 0
of O 0
valproic B-Chemical 0
acid I-Chemical 0
; O 0
a O 0
paradoxical O 0
epileptogenic O 0
effect O 0
secondary O 0
to O 0
the O 0
drug O 0
; O 0
and O 0
an O 0
indirect O 0
CNS O 0
toxic O 0
effect O 0
mediated O 0
through O 0
valproic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
hyperammonemia B-Disease 0
. O 0

Reversal O 0
of O 0
scopolamine B-Chemical 0
- O 0
induced O 0
amnesia B-Disease 0
of O 0
passive O 0
avoidance O 0
by O 0
pre O 0
- O 0
and O 0
post O 0
- O 0
training O 0
naloxone B-Chemical 0
. O 0

In O 0
a O 0
series O 0
of O 0
five O 0
experiments O 0
, O 0
the O 0
modulating O 0
role O 0
of O 0
naloxone B-Chemical 0
on O 0
a O 0
scopolamine B-Chemical 0
- O 0
induced O 0
retention B-Disease 0
deficit I-Disease 0
in O 0
a O 0
passive O 0
avoidance O 0
paradigm O 0
was O 0
investigated O 0
in O 0
mice O 0
. O 0

Scopolamine B-Chemical 0
, O 0
but O 0
not O 0
methyl B-Chemical 0
scopolamine I-Chemical 0
( O 0
1 O 0
and O 0
3 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
induced O 0
an O 0
amnesia B-Disease 0
as O 0
measured O 0
by O 0
latency O 0
and O 0
duration O 0
parameters O 0
. O 0

Naloxone B-Chemical 0
( O 0
0 O 0
. O 0
3 O 0
, O 0
1 O 0
, O 0
3 O 0
, O 0
and O 0
10 O 0
mg O 0
/ O 0
kg O 0
) O 0
injected O 0
prior O 0
to O 0
training O 0
attenuated O 0
the O 0
retention B-Disease 0
deficit I-Disease 0
with O 0
a O 0
peak O 0
of O 0
activity O 0
at O 0
3 O 0
mg O 0
/ O 0
kg O 0
. O 0

The O 0
effect O 0
of O 0
naloxone B-Chemical 0
could O 0
be O 0
antagonized O 0
with O 0
morphine B-Chemical 0
( O 0
1 O 0
, O 0
3 O 0
, O 0
and O 0
10 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
demonstrating O 0
the O 0
opioid O 0
specificity O 0
of O 0
the O 0
naloxone B-Chemical 0
effect O 0
. O 0

Post O 0
- O 0
training O 0
administration O 0
of O 0
naloxone B-Chemical 0
( O 0
3 O 0
mg O 0
/ O 0
kg O 0
) O 0
as O 0
a O 0
single O 0
or O 0
as O 0
a O 0
split O 0
dose O 0
also O 0
attenuated O 0
the O 0
scopolamine B-Chemical 0
- O 0
induced O 0
amnesia B-Disease 0
. O 0

Control O 0
experiments O 0
indicated O 0
that O 0
neither O 0
an O 0
increase O 0
in O 0
pain B-Disease 0
sensitivity O 0
( O 0
pre O 0
- O 0
training O 0
naloxone B-Chemical 0
) O 0
nor O 0
an O 0
induced O 0
aversive O 0
state O 0
( O 0
post O 0
- O 0
training O 0
naloxone B-Chemical 0
) O 0
appear O 0
to O 0
be O 0
responsible O 0
for O 0
the O 0
influence O 0
of O 0
naloxone B-Chemical 0
on O 0
the O 0
scopolamine B-Chemical 0
- O 0
induced O 0
retention B-Disease 0
deficit I-Disease 0
. O 0

These O 0
results O 0
extend O 0
previous O 0
findings O 0
implicating O 0
a O 0
cholinergic O 0
- O 0
opioid O 0
interaction O 0
in O 0
memory O 0
processes O 0
. O 0

A O 0
possible O 0
mechanism O 0
for O 0
this O 0
interaction O 0
involving O 0
the O 0
septo O 0
- O 0
hippocampal O 0
cholinergic O 0
pathway O 0
is O 0
discussed O 0
. O 0

Electron O 0
microscopic O 0
investigations O 0
of O 0
the O 0
cyclophosphamide B-Chemical 0
- O 0
induced O 0
lesions B-Disease 0
of I-Disease 0
the I-Disease 0
urinary I-Disease 0
bladder I-Disease 0
of O 0
the O 0
rat O 0
and O 0
their O 0
prevention O 0
by O 0
mesna B-Chemical 0
. O 0

Fully O 0
developed O 0
cyclophosphamide B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
is O 0
characterized O 0
by O 0
nearly O 0
complete O 0
detachment O 0
of O 0
the O 0
urothelium O 0
, O 0
severe O 0
submucosal O 0
edema B-Disease 0
owing O 0
to O 0
damage O 0
to O 0
the O 0
microvascular O 0
bed O 0
and O 0
focal O 0
muscle O 0
necroses B-Disease 0
. O 0

The O 0
initial O 0
response O 0
to O 0
the O 0
primary O 0
attack O 0
by O 0
the O 0
cyclophosphamide B-Chemical 0
metabolites O 0
seems O 0
to O 0
be O 0
fragmentation O 0
of O 0
the O 0
luminal B-Chemical 0
membrane O 0
. O 0

This O 0
damages O 0
the O 0
cellular O 0
barrier O 0
against O 0
the O 0
hypertonic O 0
urine O 0
. O 0

Subsequent O 0
breaks O 0
in O 0
the O 0
lateral O 0
cell O 0
membranes O 0
of O 0
the O 0
superficial O 0
cells O 0
and O 0
in O 0
all O 0
the O 0
plasma O 0
membranes O 0
of O 0
the O 0
intermediate O 0
and O 0
basal O 0
cells O 0
, O 0
intercellular O 0
and O 0
intracellular O 0
edema B-Disease 0
and O 0
disintegration O 0
of O 0
the O 0
desmosomes O 0
and O 0
hemidesmosomes O 0
lead O 0
to O 0
progressive O 0
degeneration O 0
and O 0
detachment O 0
of O 0
the O 0
epithelial O 0
cells O 0
with O 0
exposure O 0
and O 0
splitting O 0
of O 0
the O 0
basal O 0
membrane O 0
. O 0

The O 0
morphological O 0
changes O 0
of O 0
the O 0
endothelial O 0
cells O 0
, O 0
which O 0
become O 0
more O 0
pronounced O 0
in O 0
the O 0
later O 0
stages O 0
of O 0
the O 0
experiment O 0
, O 0
the O 0
involvement O 0
of O 0
blood O 0
vessels O 0
regardless O 0
of O 0
their O 0
diameter O 0
and O 0
the O 0
location O 0
- O 0
dependent O 0
extent O 0
of O 0
the O 0
damage O 0
indicate O 0
a O 0
direct O 0
type O 0
of O 0
damage O 0
which O 0
is O 0
preceded O 0
by O 0
a O 0
mediator O 0
- O 0
induced O 0
increase O 0
in O 0
permeability O 0
, O 0
the O 0
morphological O 0
correlate O 0
of O 0
which O 0
is O 0
the O 0
formation O 0
of O 0
gaps O 0
in O 0
the O 0
interendothelial O 0
cell O 0
connections O 0
on O 0
the O 0
venules O 0
. O 0

These O 0
changes O 0
can O 0
be O 0
effectively O 0
prevented O 0
by O 0
mesna B-Chemical 0
. O 0

The O 0
only O 0
sign O 0
of O 0
a O 0
possible O 0
involvement O 0
is O 0
the O 0
increase O 0
in O 0
the O 0
number O 0
of O 0
specific O 0
granules O 0
with O 0
a O 0
presumed O 0
lysosomal O 0
function O 0
in O 0
the O 0
superficial O 0
cells O 0
. O 0

Increase O 0
in O 0
intragastric O 0
pressure O 0
during O 0
suxamethonium B-Chemical 0
- O 0
induced O 0
muscle B-Disease 0
fasciculations I-Disease 0
in O 0
children O 0
: O 0
inhibition O 0
by O 0
alfentanil B-Chemical 0
. O 0

Changes O 0
in O 0
intragastric O 0
pressure O 0
after O 0
the O 0
administration O 0
of O 0
suxamethonium B-Chemical 0
1 O 0
. O 0
5 O 0
mg O 0
kg O 0
- O 0
1 O 0
i O 0
. O 0
v O 0
. O 0
were O 0
studied O 0
in O 0
32 O 0
children O 0
( O 0
mean O 0
age O 0
6 O 0
. O 0
9 O 0
yr O 0
) O 0
pretreated O 0
with O 0
either O 0
physiological O 0
saline O 0
or O 0
alfentanil B-Chemical 0
50 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
. O 0

Anaesthesia O 0
was O 0
induced O 0
with O 0
thiopentone B-Chemical 0
5 O 0
mg O 0
kg O 0
- O 0
1 O 0
. O 0

The O 0
incidence O 0
and O 0
intensity O 0
of O 0
muscle B-Disease 0
fasciculations I-Disease 0
caused O 0
by O 0
suxamethonium B-Chemical 0
were O 0
significantly O 0
greater O 0
in O 0
the O 0
control O 0
than O 0
in O 0
the O 0
alfentanil B-Chemical 0
group O 0
. O 0

The O 0
intragastric O 0
pressure O 0
during O 0
muscle B-Disease 0
fasciculations I-Disease 0
was O 0
significantly O 0
higher O 0
in O 0
the O 0
control O 0
group O 0
( O 0
16 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
7 O 0
( O 0
SEM O 0
) O 0
cm O 0
H2O B-Chemical 0
) O 0
than O 0
in O 0
the O 0
alfentanil B-Chemical 0
group O 0
( O 0
7 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
5 O 0
( O 0
SEM O 0
) O 0
cm O 0
H2O B-Chemical 0
) O 0
. O 0

The O 0
increase O 0
in O 0
intragastric O 0
pressure O 0
was O 0
directly O 0
related O 0
to O 0
the O 0
intensity O 0
of O 0
muscle B-Disease 0
fasciculations I-Disease 0
( O 0
regression O 0
line O 0
: O 0
y O 0
= O 0
0 O 0
. O 0
5 O 0
+ O 0
4 O 0
. O 0
78x O 0
with O 0
r O 0
of O 0
0 O 0
. O 0
78 O 0
) O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
intragastric O 0
pressure O 0
increases O 0
significantly O 0
during O 0
muscle B-Disease 0
fasciculations I-Disease 0
caused O 0
by O 0
suxamethonium B-Chemical 0
in O 0
healthy O 0
children O 0
. O 0

Alfentanil B-Chemical 0
50 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
effectively O 0
inhibits O 0
the O 0
incidence O 0
and O 0
intensity O 0
of O 0
suxamethonium B-Chemical 0
- O 0
induced O 0
muscle B-Disease 0
fasciculations I-Disease 0
; O 0
moreover O 0
, O 0
intragastric O 0
pressure O 0
remains O 0
at O 0
its O 0
control O 0
value O 0
. O 0

Acute O 0
insulin O 0
treatment O 0
normalizes O 0
the O 0
resistance O 0
to O 0
the O 0
cardiotoxic B-Disease 0
effect O 0
of O 0
isoproterenol B-Chemical 0
in O 0
streptozotocin B-Chemical 0
diabetic B-Disease 0
rats O 0
. O 0

A O 0
morphometric O 0
study O 0
of O 0
isoproterenol B-Chemical 0
induced O 0
myocardial O 0
fibrosis B-Disease 0
. O 0

The O 0
acute O 0
effect O 0
of O 0
insulin O 0
treatment O 0
on O 0
the O 0
earlier O 0
reported O 0
protective O 0
effect O 0
of O 0
streptozotocin B-Chemical 0
diabetes B-Disease 0
against O 0
the O 0
cardiotoxic B-Disease 0
effect O 0
of O 0
high O 0
doses O 0
of O 0
isoproterenol B-Chemical 0
( O 0
ISO B-Chemical 0
) O 0
was O 0
investigated O 0
in O 0
rats O 0
. O 0

Thirty O 0
to O 0
135 O 0
min O 0
after O 0
the O 0
injection O 0
of O 0
crystalline O 0
insulin O 0
, O 0
ISO B-Chemical 0
was O 0
given O 0
subcutaneously O 0
and O 0
when O 0
ISO B-Chemical 0
induced O 0
fibrosis B-Disease 0
in O 0
the O 0
myocardium O 0
was O 0
morphometrically O 0
analyzed O 0
7 O 0
days O 0
later O 0
, O 0
a O 0
highly O 0
significant O 0
correlation O 0
( O 0
r O 0
= O 0
0 O 0
. O 0
83 O 0
, O 0
2 O 0
p O 0
= O 0
0 O 0
. O 0
006 O 0
) O 0
to O 0
the O 0
slope O 0
of O 0
the O 0
fall O 0
in O 0
blood O 0
glucose B-Chemical 0
after O 0
insulin O 0
treatment O 0
appeared O 0
. O 0

The O 0
myocardial O 0
content O 0
of O 0
catecholamines B-Chemical 0
was O 0
estimated O 0
in O 0
these O 0
8 O 0
day O 0
diabetic B-Disease 0
rats O 0
. O 0

The O 0
norepinephrine B-Chemical 0
content O 0
was O 0
significantly O 0
increased O 0
while O 0
epinephrine B-Chemical 0
remained O 0
unchanged O 0
. O 0

An O 0
enhanced O 0
sympathetic O 0
nervous O 0
system O 0
activity O 0
with O 0
a O 0
consequent O 0
down O 0
regulation O 0
of O 0
the O 0
myocardial O 0
beta O 0
- O 0
adrenergic O 0
receptors O 0
could O 0
, O 0
therefore O 0
, O 0
explain O 0
this O 0
catecholamine B-Chemical 0
resistance O 0
. O 0

The O 0
rapid O 0
reversion O 0
after O 0
insulin O 0
treatment O 0
excludes O 0
the O 0
possibility O 0
that O 0
streptozotocin B-Chemical 0
in O 0
itself O 0
causes O 0
the O 0
ISO B-Chemical 0
resistance O 0
and O 0
points O 0
towards O 0
a O 0
direct O 0
insulin O 0
effect O 0
on O 0
myocardial O 0
catecholamine B-Chemical 0
sensitivity O 0
in O 0
diabetic B-Disease 0
rats O 0
. O 0

The O 0
phenomenon O 0
described O 0
might O 0
elucidate O 0
pathogenetic O 0
mechanisms O 0
behind O 0
toxic O 0
myocardial O 0
cell O 0
degeneration O 0
and O 0
may O 0
possibly O 0
have O 0
relevance O 0
for O 0
acute O 0
cardiovascular O 0
complications O 0
in O 0
diabetic B-Disease 0
patients O 0
. O 0

Differential O 0
effects O 0
of O 0
non O 0
- O 0
steroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
on O 0
seizures B-Disease 0
produced O 0
by O 0
pilocarpine B-Chemical 0
in O 0
rats O 0
. O 0

The O 0
muscarinic O 0
cholinergic O 0
agonist O 0
pilocarpine B-Chemical 0
induces O 0
in O 0
rats O 0
seizures B-Disease 0
and O 0
status B-Disease 0
epilepticus I-Disease 0
followed O 0
by O 0
widespread O 0
damage O 0
to O 0
the O 0
forebrain O 0
. O 0

The O 0
present O 0
study O 0
was O 0
designed O 0
to O 0
investigate O 0
the O 0
effect O 0
of O 0
5 O 0
non O 0
- O 0
steroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
, O 0
sodium B-Chemical 0
salicylate I-Chemical 0
, O 0
phenylbutazone B-Chemical 0
, O 0
indomethacin B-Chemical 0
, O 0
ibuprofen B-Chemical 0
and O 0
mefenamic B-Chemical 0
acid I-Chemical 0
, O 0
on O 0
seizures B-Disease 0
produced O 0
by O 0
pilocarpine B-Chemical 0
. O 0

Pretreatment O 0
of O 0
rats O 0
with O 0
sodium B-Chemical 0
salicylate I-Chemical 0
, O 0
ED50 O 0
103 O 0
mg O 0
/ O 0
kg O 0
( O 0
60 O 0
- O 0
174 O 0
) O 0
, O 0
and O 0
phenylbutazone B-Chemical 0
, O 0
59 O 0
mg O 0
/ O 0
kg O 0
( O 0
50 O 0
- O 0
70 O 0
) O 0
converted O 0
the O 0
non O 0
- O 0
convulsant O 0
dose O 0
of O 0
pilocarpine B-Chemical 0
, O 0
200 O 0
mg O 0
/ O 0
kg O 0
, O 0
to O 0
a O 0
convulsant O 0
one O 0
. O 0

Indomethacin B-Chemical 0
, O 0
1 O 0
- O 0
10 O 0
mg O 0
/ O 0
kg O 0
, O 0
and O 0
ibuprofen B-Chemical 0
, O 0
10 O 0
- O 0
100 O 0
mg O 0
/ O 0
kg O 0
, O 0
failed O 0
to O 0
modulate O 0
seizures B-Disease 0
produced O 0
by O 0
pilocarpine B-Chemical 0
. O 0

Mefenamic B-Chemical 0
acid I-Chemical 0
, O 0
26 O 0
( O 0
22 O 0
- O 0
30 O 0
) O 0
mg O 0
/ O 0
kg O 0
, O 0
prevented O 0
seizures B-Disease 0
and O 0
protected O 0
rats O 0
from O 0
seizure B-Disease 0
- O 0
related O 0
brain B-Disease 0
damage I-Disease 0
induced O 0
by O 0
pilocarpine B-Chemical 0
, O 0
380 O 0
mg O 0
/ O 0
kg O 0
. O 0

These O 0
results O 0
indicate O 0
that O 0
non O 0
- O 0
steroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
differentially O 0
modulate O 0
the O 0
threshold O 0
for O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
. O 0

Acute B-Disease 0
neurologic I-Disease 0
dysfunction I-Disease 0
after O 0
high O 0
- O 0
dose O 0
etoposide B-Chemical 0
therapy O 0
for O 0
malignant B-Disease 0
glioma I-Disease 0
. O 0

Etoposide B-Chemical 0
( O 0
VP B-Chemical 0
- I-Chemical 0
16 I-Chemical 0
- I-Chemical 0
213 I-Chemical 0
) O 0
has O 0
been O 0
used O 0
in O 0
the O 0
treatment O 0
of O 0
many O 0
solid O 0
tumors B-Disease 0
and O 0
hematologic B-Disease 0
malignancies I-Disease 0
. O 0

When O 0
used O 0
in O 0
high O 0
doses O 0
and O 0
in O 0
conjunction O 0
with O 0
autologous O 0
bone O 0
marrow O 0
transplantation O 0
, O 0
this O 0
agent O 0
has O 0
activity O 0
against O 0
several O 0
treatment O 0
- O 0
resistant O 0
cancers B-Disease 0
including O 0
malignant B-Disease 0
glioma I-Disease 0
. O 0

In O 0
six O 0
of O 0
eight O 0
patients O 0
( O 0
75 O 0
% O 0
) O 0
who O 0
we O 0
treated O 0
for O 0
recurrent O 0
or O 0
resistant O 0
glioma B-Disease 0
, O 0
sudden O 0
severe O 0
neurologic B-Disease 0
deterioration I-Disease 0
occurred O 0
. O 0

This O 0
developed O 0
a O 0
median O 0
of O 0
9 O 0
days O 0
after O 0
initiation O 0
of O 0
high O 0
- O 0
dose O 0
etoposide B-Chemical 0
therapy O 0
. O 0

Significant O 0
clinical O 0
manifestations O 0
have O 0
included O 0
confusion B-Disease 0
, O 0
papilledema B-Disease 0
, O 0
somnolence B-Disease 0
, O 0
exacerbation O 0
of O 0
motor B-Disease 0
deficits I-Disease 0
, O 0
and O 0
sharp O 0
increase O 0
in O 0
seizure B-Disease 0
activity O 0
. O 0

These O 0
abnormalities O 0
resolved O 0
rapidly O 0
after O 0
initiation O 0
of O 0
high O 0
- O 0
dose O 0
intravenous O 0
dexamethasone B-Chemical 0
therapy O 0
. O 0

In O 0
all O 0
patients O 0
, O 0
computerized O 0
tomographic O 0
( O 0
CT O 0
) O 0
brain O 0
scans O 0
demonstrated O 0
stability O 0
in O 0
tumor B-Disease 0
size O 0
and O 0
peritumor O 0
edema B-Disease 0
when O 0
compared O 0
with O 0
pretransplant O 0
scans O 0
. O 0

This O 0
complication O 0
appears O 0
to O 0
represent O 0
a O 0
significant O 0
new O 0
toxicity B-Disease 0
of O 0
high O 0
- O 0
dose O 0
etoposide B-Chemical 0
therapy O 0
for O 0
malignant B-Disease 0
glioma I-Disease 0
. O 0

Progressive O 0
bile B-Disease 0
duct I-Disease 0
injury I-Disease 0
after O 0
thiabendazole B-Chemical 0
administration O 0
. O 0

A O 0
27 O 0
- O 0
yr O 0
- O 0
old O 0
man O 0
developed O 0
jaundice B-Disease 0
2 O 0
wk O 0
after O 0
exposure O 0
to O 0
thiabendazole B-Chemical 0
. O 0

Cholestasis B-Disease 0
persisted O 0
for O 0
3 O 0
yr O 0
, O 0
at O 0
which O 0
time O 0
a O 0
liver O 0
transplant O 0
was O 0
performed O 0
. O 0

Two O 0
liver O 0
biopsy O 0
specimens O 0
and O 0
the O 0
hepatectomy O 0
specimen O 0
were O 0
remarkable O 0
for O 0
almost O 0
complete O 0
disappearance O 0
of O 0
interlobular O 0
bile O 0
ducts O 0
. O 0

Prominent O 0
fibrosis B-Disease 0
and O 0
hepatocellular O 0
regeneration O 0
were O 0
also O 0
present O 0
; O 0
however O 0
, O 0
the O 0
lobular O 0
architecture O 0
was O 0
preserved O 0
. O 0

This O 0
case O 0
represents O 0
an O 0
example O 0
of O 0
" O 0
idiosyncratic O 0
" O 0
drug B-Disease 0
- I-Disease 0
induced I-Disease 0
liver I-Disease 0
damage I-Disease 0
in O 0
which O 0
the O 0
primary O 0
target O 0
of O 0
injury O 0
is O 0
the O 0
bile O 0
duct O 0
. O 0

An O 0
autoimmune O 0
pathogenesis O 0
of O 0
the O 0
bile B-Disease 0
duct I-Disease 0
destruction I-Disease 0
is O 0
suggested O 0
. O 0

Differential O 0
effects O 0
of O 0
1 B-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
dihydropyridine I-Chemical 0
calcium B-Chemical 0
channel I-Chemical 0
blockers I-Chemical 0
: O 0
therapeutic O 0
implications O 0
. O 0

Increasing O 0
recognition O 0
of O 0
the O 0
importance O 0
of O 0
calcium B-Chemical 0
in O 0
the O 0
pathogenesis O 0
of O 0
cardiovascular B-Disease 0
disease I-Disease 0
has O 0
stimulated O 0
research O 0
into O 0
the O 0
use O 0
of O 0
calcium B-Chemical 0
channel I-Chemical 0
blocking I-Chemical 0
agents I-Chemical 0
for O 0
treatment O 0
of O 0
a O 0
variety O 0
of O 0
cardiovascular B-Disease 0
diseases I-Disease 0
. O 0

The O 0
favorable O 0
efficacy O 0
and O 0
tolerability O 0
profiles O 0
of O 0
these O 0
agents O 0
make O 0
them O 0
attractive O 0
therapeutic O 0
modalities O 0
. O 0

Clinical O 0
applications O 0
of O 0
calcium B-Chemical 0
channel I-Chemical 0
blockers I-Chemical 0
parallel O 0
their O 0
tissue O 0
selectivity O 0
. O 0

In O 0
contrast O 0
to O 0
verapamil B-Chemical 0
and O 0
diltiazem B-Chemical 0
, O 0
which O 0
are O 0
roughly O 0
equipotent O 0
in O 0
their O 0
actions O 0
on O 0
the O 0
heart O 0
and O 0
vascular O 0
smooth O 0
muscle O 0
, O 0
the O 0
dihydropyridine B-Chemical 0
calcium B-Chemical 0
channel I-Chemical 0
blockers I-Chemical 0
are O 0
a O 0
group O 0
of O 0
potent O 0
peripheral O 0
vasodilator O 0
agents O 0
that O 0
exert O 0
minimal O 0
electrophysiologic O 0
effects O 0
on O 0
cardiac O 0
nodal O 0
or O 0
conduction O 0
tissue O 0
. O 0

As O 0
the O 0
first O 0
dihydropyridine B-Chemical 0
available O 0
for O 0
use O 0
in O 0
the O 0
United O 0
States O 0
, O 0
nifedipine B-Chemical 0
controls O 0
angina B-Disease 0
and O 0
hypertension B-Disease 0
with O 0
minimal O 0
depression O 0
of O 0
cardiac O 0
function O 0
. O 0

Additional O 0
members O 0
of O 0
this O 0
group O 0
of O 0
calcium B-Chemical 0
channel I-Chemical 0
blockers I-Chemical 0
have O 0
been O 0
studied O 0
for O 0
a O 0
variety O 0
of O 0
indications O 0
for O 0
which O 0
they O 0
may O 0
offer O 0
advantages O 0
over O 0
current O 0
therapy O 0
. O 0

Once O 0
or O 0
twice O 0
daily O 0
dosage O 0
possible O 0
with O 0
nitrendipine B-Chemical 0
and O 0
nisoldipine B-Chemical 0
offers O 0
a O 0
convenient O 0
administration O 0
schedule O 0
, O 0
which O 0
encourages O 0
patient O 0
compliance O 0
in O 0
long O 0
- O 0
term O 0
therapy O 0
of O 0
hypertension B-Disease 0
. O 0

The O 0
coronary O 0
vasodilating O 0
properties O 0
of O 0
nisoldipine B-Chemical 0
have O 0
led O 0
to O 0
the O 0
investigation O 0
of O 0
this O 0
agent O 0
for O 0
use O 0
in O 0
angina B-Disease 0
. O 0

Selectivity O 0
for O 0
the O 0
cerebrovascular O 0
bed O 0
makes O 0
nimodipine B-Chemical 0
potentially O 0
useful O 0
in O 0
the O 0
treatment O 0
of O 0
subarachnoid B-Disease 0
hemorrhage I-Disease 0
, O 0
migraine B-Disease 0
headache I-Disease 0
, O 0
dementia B-Disease 0
, O 0
and O 0
stroke B-Disease 0
. O 0

In O 0
general O 0
, O 0
the O 0
dihydropyridine B-Chemical 0
calcium B-Chemical 0
channel I-Chemical 0
blockers I-Chemical 0
are O 0
usually O 0
well O 0
tolerated O 0
, O 0
with O 0
headache B-Disease 0
, O 0
facial O 0
flushing B-Disease 0
, O 0
palpitations B-Disease 0
, O 0
edema B-Disease 0
, O 0
nausea B-Disease 0
, O 0
anorexia B-Disease 0
, O 0
and O 0
dizziness B-Disease 0
being O 0
the O 0
more O 0
common O 0
adverse O 0
effects O 0
. O 0

The O 0
enhancement O 0
of O 0
aminonucleoside B-Chemical 0
nephrosis B-Disease 0
by O 0
the O 0
co O 0
- O 0
administration O 0
of O 0
protamine O 0
. O 0

An O 0
experimental O 0
model O 0
of O 0
focal B-Disease 0
segmental I-Disease 0
glomerular I-Disease 0
sclerosis I-Disease 0
( O 0
FSGS B-Disease 0
) O 0
was O 0
developed O 0
in O 0
rats O 0
by O 0
the O 0
combined O 0
administration O 0
of O 0
puromycin B-Chemical 0
- I-Chemical 0
aminonucleoside I-Chemical 0
( O 0
AMNS B-Chemical 0
) O 0
and O 0
protamine B-Chemical 0
sulfate I-Chemical 0
( O 0
PS B-Chemical 0
) O 0
. O 0

Male O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
, O 0
uninephrectomized O 0
three O 0
weeks O 0
before O 0
, O 0
received O 0
daily O 0
injections O 0
of O 0
subcutaneous O 0
AMNS B-Chemical 0
( O 0
1 O 0
mg O 0
/ O 0
100 O 0
g O 0
body O 0
wt O 0
) O 0
and O 0
intravenous O 0
PS B-Chemical 0
( O 0
2 O 0
separated O 0
doses O 0
of O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
100 O 0
g O 0
body O 0
wt O 0
) O 0
for O 0
four O 0
days O 0
. O 0

The O 0
series O 0
of O 0
injections O 0
were O 0
repeated O 0
another O 0
three O 0
times O 0
at O 0
10 O 0
day O 0
intervals O 0
. O 0

The O 0
animals O 0
were O 0
sacrificed O 0
on O 0
days O 0
24 O 0
, O 0
52 O 0
, O 0
and O 0
80 O 0
. O 0

They O 0
developed O 0
nephrotic B-Disease 0
syndrome I-Disease 0
and O 0
finally O 0
renal B-Disease 0
failure I-Disease 0
. O 0

The O 0
time O 0
- O 0
course O 0
curve O 0
of O 0
creatinine B-Chemical 0
clearance O 0
dropped O 0
and O 0
showed O 0
significant O 0
difference O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
from O 0
that O 0
of O 0
each O 0
control O 0
group O 0
, O 0
such O 0
as O 0
, O 0
AMNS B-Chemical 0
alone O 0
, O 0
PS B-Chemical 0
alone O 0
or O 0
saline O 0
injected O 0
. O 0

Their O 0
glomeruli O 0
showed O 0
changes O 0
of O 0
progressive O 0
FSGS B-Disease 0
. O 0

The O 0
ultrastructural O 0
studies O 0
in O 0
the O 0
initial O 0
stage O 0
revealed O 0
significant O 0
lack O 0
of O 0
particles O 0
of O 0
perfused O 0
ruthenium B-Chemical 0
red O 0
on O 0
the O 0
lamina O 0
rara O 0
externa O 0
and O 0
marked O 0
changes O 0
in O 0
epithelial O 0
cell O 0
cytoplasm O 0
. O 0

Therefore O 0
, O 0
it O 0
is O 0
suggested O 0
that O 0
the O 0
administration O 0
of O 0
PS B-Chemical 0
enhances O 0
the O 0
toxicity B-Disease 0
of O 0
AMNS B-Chemical 0
on O 0
the O 0
glomerulus O 0
and O 0
readily O 0
produces O 0
progressive O 0
FSGS B-Disease 0
in O 0
rats O 0
resulting O 0
in O 0
the O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
renal I-Disease 0
disease I-Disease 0
. O 0

Theophylline B-Chemical 0
neurotoxicity B-Disease 0
in O 0
pregnant O 0
rats O 0
. O 0

The O 0
purpose O 0
of O 0
this O 0
investigation O 0
was O 0
to O 0
determine O 0
whether O 0
the O 0
neurotoxicity B-Disease 0
of O 0
theophylline B-Chemical 0
is O 0
altered O 0
in O 0
advanced O 0
pregnancy O 0
. O 0

Sprague O 0
- O 0
Dawley O 0
rats O 0
that O 0
were O 0
20 O 0
days O 0
pregnant O 0
and O 0
nonpregnant O 0
rats O 0
of O 0
the O 0
same O 0
age O 0
and O 0
strain O 0
received O 0
infusions O 0
of O 0
aminophylline B-Chemical 0
until O 0
onset O 0
of O 0
maximal O 0
seizures B-Disease 0
which O 0
occurred O 0
after O 0
28 O 0
and O 0
30 O 0
minutes O 0
respectively O 0
. O 0

Theophylline B-Chemical 0
concentrations O 0
at O 0
this O 0
endpoint O 0
in O 0
serum O 0
( O 0
total O 0
) O 0
and O 0
CSF O 0
were O 0
similar O 0
but O 0
serum O 0
( O 0
free O 0
) O 0
and O 0
brain O 0
concentrations O 0
were O 0
slightly O 0
different O 0
in O 0
pregnant O 0
rats O 0
. O 0

Theophylline B-Chemical 0
serum O 0
protein O 0
binding O 0
determined O 0
by O 0
equilibrium O 0
dialysis O 0
was O 0
lower O 0
in O 0
pregnant O 0
rats O 0
. O 0

Fetal O 0
serum O 0
concentrations O 0
at O 0
onset O 0
of O 0
seizures B-Disease 0
in O 0
the O 0
mother O 0
were O 0
similar O 0
to O 0
maternal O 0
brain O 0
and O 0
CSF O 0
concentrations O 0
and O 0
correlated O 0
significantly O 0
with O 0
the O 0
former O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
advanced O 0
pregnancy O 0
has O 0
a O 0
negligible O 0
effect O 0
on O 0
the O 0
neurotoxic B-Disease 0
response O 0
to O 0
theophylline B-Chemical 0
in O 0
rats O 0
. O 0

Hyperkalemia B-Disease 0
induced O 0
by O 0
indomethacin B-Chemical 0
and O 0
naproxen B-Chemical 0
and O 0
reversed O 0
by O 0
fludrocortisone B-Chemical 0
. O 0

We O 0
have O 0
described O 0
a O 0
patient O 0
with O 0
severe O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
and O 0
a O 0
history O 0
of O 0
mefenamic B-Chemical 0
acid I-Chemical 0
nephropathy B-Disease 0
in O 0
whom O 0
hyperkalemia B-Disease 0
and O 0
inappropriate O 0
hypoaldosteronism B-Disease 0
were O 0
caused O 0
by O 0
both O 0
indomethacin B-Chemical 0
and O 0
naproxen B-Chemical 0
, O 0
without O 0
major O 0
decline O 0
in O 0
renal O 0
function O 0
. O 0

It O 0
is O 0
likely O 0
that O 0
preexisting O 0
renal B-Disease 0
disease I-Disease 0
predisposed O 0
this O 0
patient O 0
to O 0
type B-Disease 0
IV I-Disease 0
renal I-Disease 0
tubular I-Disease 0
acidosis I-Disease 0
with O 0
prostaglandin B-Chemical 0
synthetase O 0
inhibitors O 0
. O 0

Because O 0
he O 0
was O 0
unable O 0
to O 0
discontinue O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
drug O 0
therapy O 0
, O 0
fludrocortisone B-Chemical 0
was O 0
added O 0
, O 0
correcting O 0
the O 0
hyperkalemia B-Disease 0
and O 0
allowing O 0
indomethacin B-Chemical 0
therapy O 0
to O 0
be O 0
continued O 0
safely O 0
. O 0

Hypotension B-Disease 0
as O 0
a O 0
manifestation O 0
of O 0
cardiotoxicity B-Disease 0
in O 0
three O 0
patients O 0
receiving O 0
cisplatin B-Chemical 0
and O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
. O 0

Cardiac O 0
symptoms O 0
, O 0
including O 0
hypotension B-Disease 0
, O 0
developed O 0
in O 0
three O 0
patients O 0
with O 0
advanced O 0
colorectal B-Disease 0
carcinoma I-Disease 0
while O 0
being O 0
treated O 0
with O 0
cisplatin B-Chemical 0
( O 0
CDDP B-Chemical 0
) O 0
and O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
( O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
) O 0
. O 0

In O 0
two O 0
patients O 0
, O 0
hypotension B-Disease 0
was O 0
associated O 0
with O 0
severe O 0
left B-Disease 0
ventricular I-Disease 0
dysfunction I-Disease 0
. O 0

All O 0
three O 0
patients O 0
required O 0
therapy O 0
discontinuation O 0
. O 0

Cardiac O 0
enzymes O 0
remained O 0
normal O 0
despite O 0
transient O 0
electrocardiographic O 0
( O 0
EKG O 0
) O 0
changes O 0
. O 0

The O 0
presentation O 0
and O 0
cardiac O 0
evaluation O 0
( O 0
hemodynamic O 0
, O 0
echocardiographic O 0
, O 0
and O 0
scintigraphic O 0
) O 0
of O 0
these O 0
patients O 0
suggest O 0
new O 0
manifestations O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
cardiotoxicity B-Disease 0
that O 0
may O 0
be O 0
influenced O 0
by O 0
CDDP B-Chemical 0
. O 0

The O 0
possible O 0
pathophysiologic O 0
mechanisms O 0
are O 0
discussed O 0
. O 0

Fatal O 0
aplastic B-Disease 0
anemia I-Disease 0
in O 0
a O 0
patient O 0
treated O 0
with O 0
carbamazepine B-Chemical 0
. O 0

A O 0
case O 0
of O 0
fatal O 0
aplastic B-Disease 0
anemia I-Disease 0
due O 0
to O 0
carbamazepine B-Chemical 0
treatment O 0
in O 0
an O 0
epileptic B-Disease 0
woman O 0
is O 0
reported O 0
. O 0

Despite O 0
concerns O 0
of O 0
fatal O 0
bone B-Disease 0
marrow I-Disease 0
toxicity I-Disease 0
due O 0
to O 0
carbamazepine B-Chemical 0
, O 0
this O 0
is O 0
only O 0
the O 0
fourth O 0
documented O 0
and O 0
published O 0
report O 0
. O 0

Carbamazepine B-Chemical 0
is O 0
a O 0
safe O 0
drug O 0
, O 0
but O 0
physicians O 0
and O 0
patients O 0
should O 0
be O 0
aware O 0
of O 0
the O 0
exceedingly O 0
rare O 0
but O 0
potentially O 0
fatal O 0
side O 0
effects O 0
, O 0
better O 0
prevented O 0
by O 0
clinical O 0
than O 0
by O 0
laboratory O 0
monitoring O 0
. O 0

Participation O 0
of O 0
a O 0
bulbospinal O 0
serotonergic O 0
pathway O 0
in O 0
the O 0
rat O 0
brain O 0
in O 0
clonidine B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
and O 0
bradycardia B-Disease 0
. O 0

The O 0
effects O 0
of O 0
microinjection O 0
of O 0
clonidine B-Chemical 0
( O 0
1 O 0
- O 0
10 O 0
micrograms O 0
in O 0
1 O 0
microliter O 0
) O 0
into O 0
a O 0
region O 0
adjacent O 0
to O 0
the O 0
ventrolateral O 0
surface O 0
of O 0
the O 0
medulla O 0
oblongata O 0
on O 0
cardiovascular O 0
function O 0
were O 0
assessed O 0
in O 0
urethane B-Chemical 0
- O 0
anesthetized O 0
rats O 0
. O 0

Intramedullary O 0
administration O 0
of O 0
clonidine B-Chemical 0
, O 0
but O 0
not O 0
saline O 0
vehicle O 0
, O 0
caused O 0
a O 0
dose O 0
- O 0
dependent O 0
decrease O 0
in O 0
both O 0
the O 0
mean O 0
arterial O 0
pressure O 0
and O 0
the O 0
heart O 0
rate O 0
. O 0

The O 0
clonidine B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
was O 0
antagonized O 0
by O 0
prior O 0
spinal O 0
transection O 0
, O 0
but O 0
not O 0
bilateral O 0
vagotomy O 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
the O 0
clonidine B-Chemical 0
- O 0
induced O 0
bradycardia B-Disease 0
was O 0
antagonized O 0
by O 0
prior O 0
bilateral O 0
vagotomy O 0
, O 0
but O 0
not O 0
spinal O 0
transection O 0
. O 0

Furthermore O 0
, O 0
selective O 0
destruction O 0
of O 0
the O 0
spinal O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
nerves O 0
, O 0
produced O 0
by O 0
bilateral O 0
spinal O 0
injection O 0
of O 0
5 B-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
dihydroxytryptamine I-Chemical 0
, O 0
reduced O 0
the O 0
magnitude O 0
of O 0
the O 0
vasodepressor O 0
or O 0
the O 0
bradycardiac B-Disease 0
responses O 0
to O 0
clonidine B-Chemical 0
microinjected O 0
into O 0
the O 0
area O 0
near O 0
the O 0
ventrolateral O 0
surface O 0
of O 0
the O 0
medulla O 0
oblongata O 0
in O 0
rats O 0
. O 0

The O 0
data O 0
indicate O 0
that O 0
a O 0
bulbospinal O 0
serotonergic O 0
pathway O 0
is O 0
involved O 0
in O 0
development O 0
of O 0
clonidine B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
and O 0
bradycardia B-Disease 0
. O 0

The O 0
induced O 0
hypotension B-Disease 0
is O 0
brought O 0
about O 0
by O 0
a O 0
decrease O 0
in O 0
sympathetic O 0
efferent O 0
activity O 0
, O 0
whereas O 0
the O 0
induced O 0
bradycardia B-Disease 0
was O 0
due O 0
to O 0
an O 0
increase O 0
in O 0
vagal O 0
efferent O 0
activity O 0
. O 0

Hypertension B-Disease 0
in O 0
neuroblastoma B-Disease 0
induced O 0
by O 0
imipramine B-Chemical 0
. O 0

Hypertension B-Disease 0
is O 0
a O 0
well O 0
- O 0
known O 0
finding O 0
in O 0
some O 0
patients O 0
with O 0
neuroblastoma B-Disease 0
. O 0

However O 0
, O 0
it O 0
has O 0
not O 0
previously O 0
been O 0
described O 0
in O 0
association O 0
with O 0
the O 0
use O 0
of O 0
Imipramine B-Chemical 0
. O 0

We O 0
report O 0
the O 0
occurrence O 0
of O 0
severe O 0
hypertension B-Disease 0
( O 0
blood O 0
pressure O 0
190 O 0
/ O 0
160 O 0
) O 0
in O 0
a O 0
4 O 0
- O 0
year O 0
- O 0
old O 0
girl O 0
with O 0
neuroblastoma B-Disease 0
who O 0
was O 0
given O 0
Imipramine B-Chemical 0
to O 0
control O 0
a O 0
behavior B-Disease 0
disorder I-Disease 0
. O 0

It O 0
was O 0
determined O 0
later O 0
that O 0
this O 0
patient O 0
' O 0
s O 0
tumor B-Disease 0
was O 0
recurring O 0
at O 0
the O 0
time O 0
of O 0
her O 0
hypertensive B-Disease 0
episode O 0
. O 0

Since O 0
she O 0
had O 0
no O 0
blood O 0
pressure O 0
elevation O 0
at O 0
initial O 0
diagnosis O 0
and O 0
none O 0
following O 0
discontinuation O 0
of O 0
the O 0
Imipramine B-Chemical 0
( O 0
when O 0
she O 0
was O 0
in O 0
florid O 0
relapse O 0
) O 0
, O 0
we O 0
believe O 0
that O 0
this O 0
drug O 0
rather O 0
than O 0
her O 0
underlying O 0
disease O 0
alone O 0
caused O 0
her O 0
hypertension B-Disease 0
. O 0

The O 0
mechanism O 0
for O 0
this O 0
reaction O 0
is O 0
believed O 0
to O 0
be O 0
increased O 0
levels O 0
of O 0
vasoactive O 0
catecholamines B-Chemical 0
due O 0
to O 0
interference O 0
of O 0
their O 0
physiologic O 0
inactivation O 0
by O 0
Imipramine B-Chemical 0
. O 0

From O 0
this O 0
experience O 0
, O 0
we O 0
urge O 0
extreme O 0
caution O 0
in O 0
the O 0
use O 0
of O 0
tricyclic O 0
antidepressants O 0
in O 0
children O 0
with O 0
active O 0
neuroblastoma B-Disease 0
. O 0

Rechallenge O 0
of O 0
patients O 0
who O 0
developed O 0
oral B-Disease 0
candidiasis I-Disease 0
or O 0
hoarseness B-Disease 0
with O 0
beclomethasone B-Chemical 0
dipropionate I-Chemical 0
. O 0

Of O 0
158 O 0
asthmatic B-Disease 0
patients O 0
who O 0
were O 0
placed O 0
on O 0
inhaled O 0
beclomethasone B-Chemical 0
, O 0
15 O 0
( O 0
9 O 0
. O 0
5 O 0
% O 0
) O 0
developed O 0
either O 0
hoarseness B-Disease 0
( O 0
8 O 0
) O 0
, O 0
oral O 0
thrush B-Disease 0
( O 0
6 O 0
) O 0
, O 0
or O 0
both O 0
( O 0
1 O 0
) O 0
. O 0

When O 0
their O 0
adverse O 0
reactions O 0
subsided O 0
, O 0
seven O 0
of O 0
these O 0
15 O 0
patients O 0
were O 0
rechallenged O 0
with O 0
inhaled O 0
beclomethasone B-Chemical 0
. O 0

These O 0
included O 0
five O 0
cases O 0
who O 0
developed O 0
hoarseness B-Disease 0
and O 0
three O 0
who O 0
developed O 0
Candidiasis B-Disease 0
. O 0

One O 0
patient O 0
had O 0
both O 0
. O 0

Oral O 0
thrush B-Disease 0
did O 0
not O 0
recur O 0
, O 0
but O 0
60 O 0
% O 0
( O 0
3 O 0
/ O 0
5 O 0
) O 0
of O 0
patients O 0
with O 0
hoarseness B-Disease 0
had O 0
recurrence O 0
. O 0

We O 0
conclude O 0
that O 0
patients O 0
may O 0
be O 0
restarted O 0
on O 0
inhaled O 0
beclomethasone B-Chemical 0
when O 0
clinically O 0
indicated O 0
; O 0
however O 0
, O 0
because O 0
of O 0
the O 0
high O 0
recurrence O 0
rate O 0
, O 0
patients O 0
who O 0
develop O 0
hoarseness B-Disease 0
should O 0
not O 0
be O 0
re O 0
- O 0
challenged O 0
. O 0

Concomitant O 0
use O 0
of O 0
oral O 0
prednisone B-Chemical 0
and O 0
topical O 0
beclomethasone B-Chemical 0
may O 0
increase O 0
the O 0
risk O 0
of O 0
developing O 0
hoarseness B-Disease 0
or O 0
candidiasis B-Disease 0
. O 0

Cyclophosphamide B-Chemical 0
cardiotoxicity B-Disease 0
: O 0
an O 0
analysis O 0
of O 0
dosing O 0
as O 0
a O 0
risk O 0
factor O 0
. O 0

Patients O 0
who O 0
undergo O 0
bone O 0
marrow O 0
transplantation O 0
are O 0
generally O 0
immunosuppressed O 0
with O 0
a O 0
dose O 0
of O 0
cyclophosphamide B-Chemical 0
( O 0
CYA B-Chemical 0
) O 0
which O 0
is O 0
usually O 0
calculated O 0
based O 0
on O 0
the O 0
patient O 0
' O 0
s O 0
weight O 0
. O 0

At O 0
these O 0
high O 0
doses O 0
of O 0
CYA B-Chemical 0
, O 0
serious O 0
cardiotoxicity B-Disease 0
may O 0
occur O 0
, O 0
but O 0
definitive O 0
risk O 0
factors O 0
for O 0
the O 0
development O 0
of O 0
such O 0
cardiotoxicity B-Disease 0
have O 0
not O 0
been O 0
described O 0
. O 0

Since O 0
chemotherapeutic O 0
agent O 0
toxicity B-Disease 0
generally O 0
correlates O 0
with O 0
dose O 0
per O 0
body O 0
surface O 0
area O 0
, O 0
we O 0
retrospectively O 0
calculated O 0
the O 0
dose O 0
of O 0
CYA B-Chemical 0
in O 0
patients O 0
transplanted O 0
at O 0
our O 0
institution O 0
to O 0
determine O 0
whether O 0
the O 0
incidence O 0
of O 0
CYA B-Chemical 0
cardiotoxicity B-Disease 0
correlated O 0
with O 0
the O 0
dose O 0
per O 0
body O 0
surface O 0
area O 0
. O 0

Eighty O 0
patients O 0
who O 0
were O 0
to O 0
receive O 0
CYA B-Chemical 0
50 O 0
mg O 0
/ O 0
kg O 0
/ O 0
d O 0
for O 0
four O 0
days O 0
as O 0
preparation O 0
for O 0
marrow O 0
grafting O 0
underwent O 0
a O 0
total O 0
of O 0
84 O 0
transplants O 0
for O 0
aplastic B-Disease 0
anemia I-Disease 0
, O 0
Wiskott B-Disease 0
- I-Disease 0
Aldrich I-Disease 0
syndrome I-Disease 0
, O 0
or O 0
severe B-Disease 0
combined I-Disease 0
immunodeficiency I-Disease 0
syndrome I-Disease 0
. O 0

Fourteen O 0
of O 0
84 O 0
( O 0
17 O 0
% O 0
) O 0
patients O 0
had O 0
symptoms O 0
and O 0
signs O 0
consistent O 0
with O 0
CYA B-Chemical 0
cardiotoxicity B-Disease 0
within O 0
ten O 0
days O 0
of O 0
receiving O 0
1 O 0
to O 0
4 O 0
doses O 0
of O 0
CYA B-Chemical 0
. O 0

Six O 0
of O 0
the O 0
14 O 0
patients O 0
died O 0
with O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
. O 0

The O 0
dose O 0
of O 0
CYA B-Chemical 0
per O 0
body O 0
surface O 0
area O 0
was O 0
calculated O 0
for O 0
all O 0
patients O 0
and O 0
the O 0
patients O 0
were O 0
divided O 0
into O 0
two O 0
groups O 0
based O 0
on O 0
daily O 0
CYA B-Chemical 0
dose O 0
: O 0
Group O 0
1 O 0
, O 0
CYA B-Chemical 0
less O 0
than O 0
or O 0
equal O 0
to O 0
1 O 0
. O 0
55 O 0
g O 0
/ O 0
m2 O 0
/ O 0
d O 0
; O 0
Group O 0
2 O 0
, O 0
CYA B-Chemical 0
greater O 0
than O 0
1 O 0
. O 0
55 O 0
g O 0
/ O 0
m2 O 0
/ O 0
d O 0
. O 0

Cardiotoxicity B-Disease 0
that O 0
was O 0
thought O 0
to O 0
be O 0
related O 0
to O 0
CYA B-Chemical 0
occurred O 0
in O 0
1 O 0
/ O 0
32 O 0
( O 0
3 O 0
% O 0
) O 0
of O 0
patients O 0
in O 0
Group O 0
1 O 0
and O 0
in O 0
13 O 0
/ O 0
52 O 0
( O 0
25 O 0
% O 0
) O 0
patients O 0
in O 0
Group O 0
2 O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
025 O 0
) O 0
. O 0

Congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
caused O 0
or O 0
contributed O 0
to O 0
death O 0
in O 0
0 O 0
/ O 0
32 O 0
patients O 0
in O 0
Group O 0
1 O 0
v O 0
6 O 0
/ O 0
52 O 0
( O 0
12 O 0
% O 0
) O 0
of O 0
patients O 0
in O 0
Group O 0
2 O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
25 O 0
) O 0
. O 0

There O 0
was O 0
no O 0
difference O 0
in O 0
the O 0
rate O 0
of O 0
engraftment O 0
of O 0
evaluable O 0
patients O 0
in O 0
the O 0
two O 0
groups O 0
( O 0
P O 0
greater O 0
than O 0
0 O 0
. O 0
5 O 0
) O 0
. O 0

We O 0
conclude O 0
that O 0
the O 0
CYA B-Chemical 0
cardiotoxicity B-Disease 0
correlates O 0
with O 0
CYA B-Chemical 0
dosage O 0
as O 0
calculated O 0
by O 0
body O 0
surface O 0
area O 0
, O 0
and O 0
that O 0
patients O 0
with O 0
aplastic B-Disease 0
anemia I-Disease 0
and O 0
immunodeficiencies B-Disease 0
can O 0
be O 0
effectively O 0
prepared O 0
for O 0
bone O 0
marrow O 0
grafting O 0
at O 0
a O 0
CYA B-Chemical 0
dose O 0
of O 0
1 O 0
. O 0
55 O 0
g O 0
/ O 0
m2 O 0
/ O 0
d O 0
for O 0
four O 0
days O 0
with O 0
a O 0
lower O 0
incidence O 0
of O 0
cardiotoxicity B-Disease 0
than O 0
patients O 0
whose O 0
CYA B-Chemical 0
dosage O 0
is O 0
calculated O 0
based O 0
on O 0
weight O 0
. O 0

This O 0
study O 0
reaffirms O 0
the O 0
principle O 0
that O 0
drug O 0
toxicity B-Disease 0
correlates O 0
with O 0
dose O 0
per O 0
body O 0
surface O 0
area O 0
. O 0

Studies O 0
of O 0
risk O 0
factors O 0
for O 0
aminoglycoside B-Chemical 0
nephrotoxicity B-Disease 0
. O 0

The O 0
epidemiology O 0
of O 0
aminoglycoside B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
is O 0
not O 0
fully O 0
understood O 0
. O 0

Experimental O 0
studies O 0
in O 0
healthy O 0
human O 0
volunteers O 0
indicate O 0
aminoglycosides B-Chemical 0
cause O 0
proximal O 0
tubular O 0
damage O 0
in O 0
most O 0
patients O 0
, O 0
but O 0
rarely O 0
, O 0
if O 0
ever O 0
, O 0
cause O 0
glomerular B-Disease 0
or I-Disease 0
tubular I-Disease 0
dysfunction I-Disease 0
. O 0

Clinical O 0
trials O 0
of O 0
aminoglycosides B-Chemical 0
in O 0
seriously O 0
ill O 0
patients O 0
indicate O 0
that O 0
the O 0
relative O 0
risk O 0
for O 0
developing O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
during O 0
therapy O 0
ranges O 0
from O 0
8 O 0
to O 0
10 O 0
and O 0
that O 0
the O 0
attributable O 0
risk O 0
is O 0
70 O 0
% O 0
to O 0
80 O 0
% O 0
. O 0

Further O 0
analysis O 0
of O 0
these O 0
data O 0
suggests O 0
that O 0
the O 0
duration O 0
of O 0
therapy O 0
, O 0
plasma O 0
aminoglycoside B-Chemical 0
levels O 0
, O 0
liver B-Disease 0
disease I-Disease 0
, O 0
advanced O 0
age O 0
, O 0
high O 0
initial O 0
estimated O 0
creatinine B-Chemical 0
clearance O 0
and O 0
, O 0
possibly O 0
, O 0
female O 0
gender O 0
all O 0
increase O 0
the O 0
risk O 0
for O 0
nephrotoxicity B-Disease 0
. O 0

Other O 0
causes O 0
of O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
, O 0
such O 0
as O 0
shock B-Disease 0
, O 0
appear O 0
to O 0
have O 0
an O 0
additive O 0
effect O 0
. O 0

Predictive O 0
models O 0
have O 0
been O 0
developed O 0
from O 0
these O 0
analyses O 0
that O 0
should O 0
be O 0
useful O 0
for O 0
identifying O 0
patients O 0
at O 0
high O 0
risk O 0
. O 0

These O 0
models O 0
may O 0
also O 0
be O 0
useful O 0
in O 0
developing O 0
insights O 0
into O 0
the O 0
pathophysiology O 0
of O 0
aminoglycoside B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
. O 0

Central O 0
action O 0
of O 0
narcotic O 0
analgesics O 0
. O 0

Part O 0
IV O 0
. O 0

Noradrenergic O 0
influences O 0
on O 0
the O 0
activity O 0
of O 0
analgesics O 0
in O 0
rats O 0
. O 0

The O 0
effect O 0
of O 0
clonidine B-Chemical 0
, O 0
naphazoline B-Chemical 0
and O 0
xylometazoline B-Chemical 0
on O 0
analgesia O 0
induced O 0
by O 0
morphine B-Chemical 0
, O 0
codeine B-Chemical 0
, O 0
fentanyl B-Chemical 0
and O 0
pentazocine B-Chemical 0
, O 0
and O 0
on O 0
cataleptic B-Disease 0
effect O 0
of O 0
morphine B-Chemical 0
, O 0
codine B-Chemical 0
and O 0
fentanyl B-Chemical 0
was O 0
studied O 0
in O 0
rats O 0
. O 0

The O 0
biochemical O 0
assays O 0
on O 0
the O 0
influence O 0
of O 0
four O 0
analgesics O 0
on O 0
the O 0
brain O 0
concentration O 0
and O 0
turnover O 0
of O 0
noradrenaline B-Chemical 0
( O 0
NA B-Chemical 0
) O 0
were O 0
also O 0
performed O 0
. O 0

It O 0
was O 0
found O 0
that O 0
three O 0
drugs O 0
stimulating O 0
central O 0
NA B-Chemical 0
receptors O 0
failed O 0
to O 0
affect O 0
the O 0
analgesic O 0
ED50 O 0
of O 0
all O 0
antinociceptive O 0
agents O 0
and O 0
they O 0
enhanced O 0
catalepsy B-Disease 0
induced O 0
by O 0
morphine B-Chemical 0
and O 0
fentanyl B-Chemical 0
. O 0

Codeine B-Chemical 0
catalepsy B-Disease 0
was O 0
increased O 0
by O 0
clonidine B-Chemical 0
and O 0
decreased O 0
by O 0
naphazoline B-Chemical 0
and O 0
xylometazoline B-Chemical 0
. O 0

The O 0
brain O 0
concentration O 0
of O 0
NA B-Chemical 0
was O 0
not O 0
changed O 0
by O 0
morphine B-Chemical 0
and O 0
fentanyl B-Chemical 0
, O 0
but O 0
one O 0
of O 0
the O 0
doses O 0
of O 0
codeine B-Chemical 0
( O 0
45 O 0
mg O 0
/ O 0
kg O 0
) O 0
slightly O 0
enhanced O 0
it O 0
. O 0

Pentazocine B-Chemical 0
dose O 0
- O 0
dependently O 0
decreased O 0
the O 0
brain O 0
level O 0
of O 0
NA B-Chemical 0
. O 0

The O 0
rate O 0
of O 0
NA B-Chemical 0
turnover O 0
was O 0
not O 0
altered O 0
by O 0
analgesics O 0
except O 0
for O 0
the O 0
higher O 0
dose O 0
of O 0
fentanyl B-Chemical 0
( O 0
0 O 0
. O 0
2 O 0
mg O 0
/ O 0
kg O 0
) O 0
following O 0
which O 0
the O 0
disappearance O 0
of O 0
NA B-Chemical 0
from O 0
the O 0
brain O 0
was O 0
diminished O 0
. O 0

The O 0
results O 0
are O 0
discussed O 0
in O 0
the O 0
light O 0
of O 0
various O 0
and O 0
non O 0
- O 0
uniform O 0
data O 0
from O 0
the O 0
literature O 0
. O 0

It O 0
is O 0
suggested O 0
that O 0
in O 0
rats O 0
the O 0
brain O 0
NA B-Chemical 0
plays O 0
a O 0
less O 0
important O 0
function O 0
than O 0
the O 0
other O 0
monoamines B-Chemical 0
in O 0
the O 0
behavioural O 0
activity O 0
of O 0
potent O 0
analgesics O 0
. O 0

Flurothyl B-Chemical 0
seizure B-Disease 0
thresholds O 0
in O 0
mice O 0
treated O 0
neonatally O 0
with O 0
a O 0
single O 0
injection O 0
of O 0
monosodium B-Chemical 0
glutamate I-Chemical 0
( O 0
MSG B-Chemical 0
) O 0
: O 0
evaluation O 0
of O 0
experimental O 0
parameters O 0
in O 0
flurothyl B-Chemical 0
seizure B-Disease 0
testing O 0
. O 0

Monosodium B-Chemical 0
glutamate I-Chemical 0
( O 0
MSG B-Chemical 0
) O 0
administration O 0
to O 0
neonatal O 0
rodents O 0
produces O 0
convulsions B-Disease 0
and O 0
results O 0
in O 0
numerous O 0
biochemical O 0
and O 0
behavioral O 0
deficits O 0
. O 0

These O 0
studies O 0
were O 0
undertaken O 0
to O 0
determine O 0
if O 0
neonatal O 0
administration O 0
of O 0
MSG B-Chemical 0
produced O 0
permanent O 0
alterations O 0
in O 0
seizure B-Disease 0
susceptibility O 0
, O 0
since O 0
previous O 0
investigations O 0
were O 0
inconclusive O 0
. O 0

A O 0
flurothyl B-Chemical 0
ether B-Chemical 0
seizure B-Disease 0
screening O 0
technique O 0
was O 0
used O 0
to O 0
evaluate O 0
seizure B-Disease 0
susceptibility O 0
in O 0
adult O 0
mice O 0
that O 0
received O 0
neonatal O 0
injections O 0
of O 0
MSG B-Chemical 0
( O 0
4 O 0
mg O 0
/ O 0
g O 0
and O 0
1 O 0
mg O 0
/ O 0
g O 0
) O 0
. O 0

MSG B-Chemical 0
treatment O 0
resulted O 0
in O 0
significant O 0
reductions O 0
in O 0
whole O 0
brain O 0
weight O 0
but O 0
did O 0
not O 0
alter O 0
seizure B-Disease 0
threshold O 0
. O 0

A O 0
naloxone B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
challenge O 0
was O 0
also O 0
ineffective O 0
in O 0
altering O 0
the O 0
seizure B-Disease 0
thresholds O 0
of O 0
either O 0
control O 0
of O 0
MSG B-Chemical 0
- O 0
treated O 0
mice O 0
. O 0

Flurothyl B-Chemical 0
ether B-Chemical 0
produced O 0
hypothermia B-Disease 0
which O 0
was O 0
correlated O 0
with O 0
the O 0
duration O 0
of O 0
flurothyl B-Chemical 0
exposure O 0
; O 0
however O 0
, O 0
the O 0
relationship O 0
of O 0
hypothermia B-Disease 0
to O 0
seizure B-Disease 0
induction O 0
was O 0
unclear O 0
. O 0

Flurothyl B-Chemical 0
seizure B-Disease 0
testing O 0
proved O 0
to O 0
be O 0
a O 0
rapid O 0
and O 0
reliable O 0
technique O 0
with O 0
which O 0
to O 0
evaluate O 0
seizure B-Disease 0
susceptibility O 0
. O 0

Susceptibility O 0
to O 0
seizures B-Disease 0
produced O 0
by O 0
pilocarpine B-Chemical 0
in O 0
rats O 0
after O 0
microinjection O 0
of O 0
isoniazid B-Chemical 0
or O 0
gamma B-Chemical 0
- I-Chemical 0
vinyl I-Chemical 0
- I-Chemical 0
GABA I-Chemical 0
into O 0
the O 0
substantia O 0
nigra O 0
. O 0

Pilocarpine B-Chemical 0
, O 0
given O 0
intraperitoneally O 0
to O 0
rats O 0
, O 0
reproduces O 0
the O 0
neuropathological O 0
sequelae O 0
of O 0
temporal B-Disease 0
lobe I-Disease 0
epilepsy I-Disease 0
and O 0
provides O 0
a O 0
relevant O 0
animal O 0
model O 0
for O 0
studying O 0
mechanisms O 0
of O 0
buildup O 0
of O 0
convulsive B-Disease 0
activity O 0
and O 0
pathways O 0
operative O 0
in O 0
the O 0
generalization O 0
and O 0
propagation O 0
of O 0
seizures B-Disease 0
within O 0
the O 0
forebrain O 0
. O 0

In O 0
the O 0
present O 0
study O 0
, O 0
the O 0
effects O 0
of O 0
manipulating O 0
the O 0
activity O 0
of O 0
the O 0
gamma B-Chemical 0
- I-Chemical 0
aminobutyric I-Chemical 0
acid I-Chemical 0
( O 0
GABA B-Chemical 0
) O 0
- O 0
mediated O 0
synaptic O 0
inhibition O 0
within O 0
the O 0
substantia O 0
nigra O 0
on O 0
seizures B-Disease 0
produced O 0
by O 0
pilocarpine B-Chemical 0
in O 0
rats O 0
, O 0
were O 0
investigated O 0
. O 0

In O 0
animals O 0
pretreated O 0
with O 0
microinjections O 0
of O 0
isoniazid B-Chemical 0
, O 0
150 O 0
micrograms O 0
, O 0
an O 0
inhibitor O 0
of O 0
activity O 0
of O 0
the O 0
GABA B-Chemical 0
- O 0
synthesizing O 0
enzyme O 0
, O 0
L B-Chemical 0
- I-Chemical 0
glutamic I-Chemical 0
acid I-Chemical 0
decarboxylase O 0
, O 0
into O 0
the O 0
substantia O 0
nigra O 0
pars O 0
reticulata O 0
( O 0
SNR O 0
) O 0
, O 0
bilaterally O 0
, O 0
non O 0
- O 0
convulsant O 0
doses O 0
of O 0
pilocarpine B-Chemical 0
, O 0
100 O 0
and O 0
200 O 0
mg O 0
/ O 0
kg O 0
, O 0
resulted O 0
in O 0
severe O 0
motor O 0
limbic O 0
seizures B-Disease 0
and O 0
status B-Disease 0
epilepticus I-Disease 0
. O 0

Electroencephalographic O 0
and O 0
behavioral O 0
monitoring O 0
revealed O 0
a O 0
profound O 0
reduction O 0
of O 0
the O 0
threshold O 0
for O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
. O 0

Morphological O 0
analysis O 0
of O 0
frontal O 0
forebrain O 0
sections O 0
with O 0
light O 0
microscopy O 0
revealed O 0
seizure B-Disease 0
- O 0
related O 0
damage O 0
to O 0
the O 0
hippocampal O 0
formation O 0
, O 0
thalamus O 0
, O 0
amygdala O 0
, O 0
olfactory O 0
cortex O 0
, O 0
substantia O 0
nigra O 0
and O 0
neocortex O 0
, O 0
which O 0
is O 0
typically O 0
observed O 0
with O 0
pilocarpine B-Chemical 0
in O 0
doses O 0
exceeding O 0
350 O 0
mg O 0
/ O 0
kg O 0
. O 0

Bilateral O 0
intrastriatal O 0
injections O 0
of O 0
isoniazid B-Chemical 0
did O 0
not O 0
augment O 0
seizures B-Disease 0
produced O 0
by O 0
pilocarpine B-Chemical 0
, O 0
200 O 0
mg O 0
/ O 0
kg O 0
. O 0

Application O 0
of O 0
an O 0
irreversible O 0
inhibitor O 0
of O 0
GABA B-Chemical 0
transaminase O 0
, O 0
gamma B-Chemical 0
- I-Chemical 0
vinyl I-Chemical 0
- I-Chemical 0
GABA I-Chemical 0
( O 0
D B-Chemical 0
, I-Chemical 0
L I-Chemical 0
- I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
amino I-Chemical 0
- I-Chemical 0
hex I-Chemical 0
- I-Chemical 0
5 I-Chemical 0
- I-Chemical 0
enoic I-Chemical 0
acid I-Chemical 0
) O 0
, O 0
5 O 0
micrograms O 0
, O 0
into O 0
the O 0
SNR O 0
, O 0
bilaterally O 0
, O 0
suppressed O 0
the O 0
appearance O 0
of O 0
electrographic O 0
and O 0
behavioral O 0
seizures B-Disease 0
produced O 0
by O 0
pilocarpine B-Chemical 0
, O 0
380 O 0
mg O 0
/ O 0
kg O 0
. O 0

This O 0
treatment O 0
was O 0
also O 0
sufficient O 0
to O 0
protect O 0
animals O 0
from O 0
the O 0
occurrence O 0
of O 0
brain B-Disease 0
damage I-Disease 0
. O 0

Microinjections O 0
of O 0
gamma B-Chemical 0
- I-Chemical 0
vinyl I-Chemical 0
- I-Chemical 0
GABA I-Chemical 0
, O 0
5 O 0
micrograms O 0
, O 0
into O 0
the O 0
dorsal O 0
striatum O 0
, O 0
bilaterally O 0
, O 0
failed O 0
to O 0
prevent O 0
the O 0
development O 0
of O 0
convulsions B-Disease 0
produced O 0
by O 0
pilocarpine B-Chemical 0
, O 0
380 O 0
mg O 0
/ O 0
kg O 0
. O 0

The O 0
results O 0
demonstrate O 0
that O 0
the O 0
threshold O 0
for O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
in O 0
rats O 0
is O 0
subjected O 0
to O 0
the O 0
regulation O 0
of O 0
the O 0
GABA B-Chemical 0
- O 0
mediated O 0
synaptic O 0
inhibition O 0
within O 0
the O 0
substantia O 0
nigra O 0
. O 0

Human O 0
and O 0
canine O 0
ventricular O 0
vasoactive O 0
intestinal O 0
polypeptide O 0
: O 0
decrease O 0
with O 0
heart B-Disease 0
failure I-Disease 0
. O 0

Vasoactive O 0
intestinal O 0
polypeptide O 0
( O 0
VIP O 0
) O 0
is O 0
a O 0
systemic O 0
and O 0
coronary O 0
vasodilator O 0
that O 0
may O 0
have O 0
positive O 0
inotropic O 0
properties O 0
. O 0

Myocardial O 0
levels O 0
of O 0
VIP O 0
were O 0
assayed O 0
before O 0
and O 0
after O 0
the O 0
development O 0
of O 0
heart B-Disease 0
failure I-Disease 0
in O 0
two O 0
canine O 0
models O 0
. O 0

In O 0
the O 0
first O 0
, O 0
cobalt B-Chemical 0
cardiomyopathy B-Disease 0
was O 0
induced O 0
in O 0
eight O 0
dogs O 0
; O 0
VIP O 0
( O 0
by O 0
radioimmunoassay O 0
) O 0
decreased O 0
from O 0
35 O 0
+ O 0
/ O 0
- O 0
11 O 0
pg O 0
/ O 0
mg O 0
protein O 0
( O 0
mean O 0
+ O 0
/ O 0
- O 0
SD O 0
) O 0
to O 0
5 O 0
+ O 0
/ O 0
- O 0
4 O 0
pg O 0
/ O 0
mg O 0
protein O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

In O 0
six O 0
dogs O 0
with O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
heart B-Disease 0
failure I-Disease 0
, O 0
VIP O 0
decreased O 0
from O 0
31 O 0
+ O 0
/ O 0
- O 0
7 O 0
to O 0
11 O 0
+ O 0
/ O 0
- O 0
4 O 0
pg O 0
/ O 0
mg O 0
protein O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

In O 0
addition O 0
, O 0
VIP O 0
content O 0
of O 0
left O 0
ventricular O 0
muscle O 0
of O 0
resected O 0
failing O 0
hearts O 0
in O 0
10 O 0
patients O 0
receiving O 0
a O 0
heart O 0
transplant O 0
was O 0
compared O 0
with O 0
the O 0
papillary O 0
muscles O 0
in O 0
14 O 0
patients O 0
( O 0
five O 0
with O 0
rheumatic B-Disease 0
disease I-Disease 0
, O 0
nine O 0
with O 0
myxomatous B-Disease 0
degeneration I-Disease 0
) O 0
receiving O 0
mitral O 0
valve O 0
prostheses O 0
. O 0

The O 0
lowest O 0
myocardial O 0
VIP O 0
concentration O 0
was O 0
found O 0
in O 0
the O 0
hearts O 0
of O 0
patients O 0
with O 0
coronary B-Disease 0
disease I-Disease 0
( O 0
one O 0
patient O 0
receiving O 0
a O 0
transplant O 0
and O 0
three O 0
receiving O 0
mitral O 0
prostheses O 0
) O 0
( O 0
6 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
9 O 0
pg O 0
/ O 0
mg O 0
protein O 0
) O 0
. O 0

The O 0
other O 0
patients O 0
undergoing O 0
transplantation O 0
had O 0
an O 0
average O 0
ejection O 0
fraction O 0
of O 0
17 O 0
% O 0
+ O 0
/ O 0
- O 0
6 O 0
% O 0
and O 0
a O 0
VIP O 0
level O 0
of O 0
8 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
9 O 0
pg O 0
/ O 0
mg O 0
protein O 0
. O 0

The O 0
hearts O 0
without O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
( O 0
average O 0
ejection O 0
fraction O 0
of O 0
this O 0
group O 0
62 O 0
% O 0
+ O 0
/ O 0
- O 0
10 O 0
% O 0
) O 0
had O 0
a O 0
VIP O 0
concentration O 0
of O 0
14 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
7 O 0
. O 0
9 O 0
pg O 0
/ O 0
mg O 0
protein O 0
, O 0
and O 0
this O 0
was O 0
greater O 0
than O 0
in O 0
hearts O 0
of O 0
the O 0
patients O 0
with O 0
coronary B-Disease 0
disease I-Disease 0
and O 0
the O 0
hearts O 0
of O 0
patients O 0
receiving O 0
a O 0
transplant O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Myocardial O 0
catecholamines B-Chemical 0
were O 0
also O 0
determined O 0
in O 0
14 O 0
subjects O 0
; O 0
a O 0
weak O 0
correlation O 0
( O 0
r O 0
= O 0
0 O 0
. O 0
57 O 0
, O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
between O 0
the O 0
tissue O 0
concentrations O 0
of O 0
VIP O 0
and O 0
norepinephrine B-Chemical 0
was O 0
noted O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Non O 0
- O 0
invasive O 0
detection O 0
of O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
by O 0
body O 0
surface O 0
electrocardiographic O 0
mapping O 0
after O 0
dipyridamole B-Chemical 0
infusion O 0
. O 0

Electrocardiographic O 0
changes O 0
after O 0
dipyridamole B-Chemical 0
infusion O 0
( O 0
0 O 0
. O 0
568 O 0
mg O 0
/ O 0
kg O 0
/ O 0
4 O 0
min O 0
) O 0
were O 0
studied O 0
in O 0
41 O 0
patients O 0
with O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
and O 0
compared O 0
with O 0
those O 0
after O 0
submaximal O 0
treadmill O 0
exercise O 0
by O 0
use O 0
of O 0
the O 0
body O 0
surface O 0
mapping O 0
technique O 0
. O 0

Patients O 0
were O 0
divided O 0
into O 0
three O 0
groups O 0
; O 0
19 O 0
patients O 0
without O 0
myocardial B-Disease 0
infarction I-Disease 0
( O 0
non O 0
- O 0
MI B-Disease 0
group O 0
) O 0
, O 0
14 O 0
with O 0
anterior B-Disease 0
infarction I-Disease 0
( O 0
ANT B-Disease 0
- I-Disease 0
MI I-Disease 0
) O 0
and O 0
eight O 0
with O 0
inferior B-Disease 0
infarction I-Disease 0
( O 0
INF B-Disease 0
- I-Disease 0
MI I-Disease 0
) O 0
. O 0

Eighty O 0
- O 0
seven O 0
unipolar O 0
electrocardiograms O 0
( O 0
ECGs O 0
) O 0
distributed O 0
over O 0
the O 0
entire O 0
thoracic O 0
surface O 0
were O 0
simultaneously O 0
recorded O 0
. O 0

After O 0
dipyridamole B-Chemical 0
, O 0
ischemic B-Disease 0
ST O 0
- O 0
segment O 0
depression B-Disease 0
( O 0
0 O 0
. O 0
05 O 0
mV O 0
or O 0
more O 0
) O 0
was O 0
observed O 0
in O 0
84 O 0
% O 0
of O 0
the O 0
non O 0
- O 0
MI B-Disease 0
group O 0
, O 0
29 O 0
% O 0
of O 0
the O 0
ANT B-Disease 0
- I-Disease 0
MI I-Disease 0
group O 0
, O 0
63 O 0
% O 0
of O 0
the O 0
INF B-Disease 0
- I-Disease 0
MI I-Disease 0
group O 0
and O 0
61 O 0
% O 0
of O 0
the O 0
total O 0
population O 0
. O 0

Exercise O 0
- O 0
induced O 0
ST O 0
depression B-Disease 0
was O 0
observed O 0
in O 0
84 O 0
% O 0
of O 0
the O 0
non O 0
- O 0
MI B-Disease 0
group O 0
, O 0
43 O 0
% O 0
of O 0
the O 0
ANT B-Disease 0
- I-Disease 0
MI I-Disease 0
group O 0
, O 0
38 O 0
% O 0
of O 0
the O 0
INF B-Disease 0
- I-Disease 0
MI I-Disease 0
group O 0
and O 0
61 O 0
% O 0
of O 0
the O 0
total O 0
. O 0

For O 0
individual O 0
patients O 0
, O 0
there O 0
were O 0
no O 0
obvious O 0
differences O 0
between O 0
the O 0
body O 0
surface O 0
distribution O 0
of O 0
ST O 0
depression B-Disease 0
in O 0
both O 0
tests O 0
. O 0

The O 0
increase O 0
in O 0
pressure O 0
rate O 0
product O 0
after O 0
dipyridamole B-Chemical 0
was O 0
significantly O 0
less O 0
than O 0
that O 0
during O 0
the O 0
treadmill O 0
exercise O 0
. O 0

The O 0
data O 0
suggest O 0
that O 0
the O 0
dipyridamole B-Chemical 0
- O 0
induced O 0
myocardial B-Disease 0
ischemia I-Disease 0
is O 0
caused O 0
by O 0
the O 0
inhomogenous O 0
distribution O 0
of O 0
myocardial O 0
blood O 0
flow O 0
. O 0

We O 0
conclude O 0
that O 0
the O 0
dipyridamole B-Chemical 0
ECG O 0
test O 0
is O 0
as O 0
useful O 0
as O 0
the O 0
exercise O 0
ECG O 0
test O 0
for O 0
the O 0
assessment O 0
of O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
. O 0

Bradycardia B-Disease 0
after O 0
high O 0
- O 0
dose O 0
intravenous O 0
methylprednisolone B-Chemical 0
therapy O 0
. O 0

In O 0
5 O 0
consecutive O 0
patients O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
who O 0
received O 0
intravenous O 0
high O 0
- O 0
dose O 0
methylprednisolone B-Chemical 0
( O 0
MP B-Chemical 0
) O 0
therapy O 0
( O 0
1 O 0
g O 0
daily O 0
for O 0
2 O 0
or O 0
3 O 0
consecutive O 0
days O 0
) O 0
, O 0
a O 0
decline O 0
in O 0
pulse O 0
rate O 0
was O 0
observed O 0
, O 0
most O 0
pronounced O 0
on O 0
day O 0
4 O 0
. O 0

In O 0
one O 0
of O 0
the O 0
5 O 0
patients O 0
the O 0
bradycardia B-Disease 0
was O 0
associated O 0
with O 0
complaints O 0
of O 0
substernal O 0
pressure O 0
. O 0

Reversal O 0
to O 0
normal O 0
heart O 0
rate O 0
was O 0
found O 0
on O 0
day O 0
7 O 0
. O 0

Electrocardiographic O 0
registrations O 0
showed O 0
sinus B-Disease 0
bradycardia I-Disease 0
in O 0
all O 0
cases O 0
. O 0

No O 0
significant O 0
changes O 0
in O 0
plasma O 0
concentrations O 0
of O 0
electrolytes O 0
were O 0
found O 0
. O 0

Careful O 0
observation O 0
of O 0
patients O 0
receiving O 0
high O 0
- O 0
dose O 0
MP B-Chemical 0
is O 0
recommended O 0
. O 0

High O 0
- O 0
dose O 0
MP B-Chemical 0
may O 0
be O 0
contraindicated O 0
in O 0
patients O 0
with O 0
known O 0
heart B-Disease 0
disease I-Disease 0
. O 0

Two O 0
cases O 0
of O 0
downbeat B-Disease 0
nystagmus I-Disease 0
and O 0
oscillopsia B-Disease 0
associated O 0
with O 0
carbamazepine B-Chemical 0
. O 0

Downbeat B-Disease 0
nystagmus I-Disease 0
is O 0
often O 0
associated O 0
with O 0
structural O 0
lesions O 0
at O 0
the O 0
craniocervical O 0
junction O 0
, O 0
but O 0
has O 0
occasionally O 0
been O 0
reported O 0
as O 0
a O 0
manifestation O 0
of O 0
metabolic O 0
imbalance O 0
or O 0
drug O 0
intoxication O 0
. O 0

We O 0
recorded O 0
the O 0
eye O 0
movements O 0
of O 0
two O 0
patients O 0
with O 0
reversible O 0
downbeat B-Disease 0
nystagmus I-Disease 0
related O 0
to O 0
carbamazepine B-Chemical 0
therapy O 0
. O 0

The O 0
nystagmus B-Disease 0
of O 0
both O 0
patients O 0
resolved O 0
after O 0
reduction O 0
of O 0
the O 0
serum O 0
carbamazepine B-Chemical 0
levels O 0
. O 0

Neuroradiologic O 0
investigations O 0
including O 0
magnetic O 0
resonance O 0
imaging O 0
scans O 0
in O 0
both O 0
patients O 0
showed O 0
no O 0
evidence O 0
of O 0
intracranial O 0
abnormality O 0
. O 0

In O 0
patients O 0
with O 0
downbeat B-Disease 0
nystagmus I-Disease 0
who O 0
are O 0
taking O 0
anticonvulsant O 0
medications O 0
, O 0
consideration O 0
should O 0
be O 0
given O 0
to O 0
reduction O 0
in O 0
dose O 0
before O 0
further O 0
investigation O 0
is O 0
undertaken O 0
. O 0

Improvement O 0
by O 0
denopamine B-Chemical 0
( O 0
TA B-Chemical 0
- I-Chemical 0
064 I-Chemical 0
) O 0
of O 0
pentobarbital B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
failure I-Disease 0
in O 0
the O 0
dog O 0
heart O 0
- O 0
lung O 0
preparation O 0
. O 0

The O 0
efficacy O 0
of O 0
denopamine B-Chemical 0
, O 0
an O 0
orally O 0
active O 0
beta O 0
1 O 0
- O 0
adrenoceptor O 0
agonist O 0
, O 0
in O 0
improving O 0
cardiac B-Disease 0
failure I-Disease 0
was O 0
assessed O 0
in O 0
dog O 0
heart O 0
- O 0
lung O 0
preparations O 0
. O 0

Cardiac O 0
functions O 0
depressed O 0
by O 0
pentobarbital B-Chemical 0
( O 0
118 O 0
+ O 0
/ O 0
- O 0
28 O 0
mg O 0
; O 0
mean O 0
value O 0
+ O 0
/ O 0
- O 0
SD O 0
) O 0
such O 0
that O 0
cardiac O 0
output O 0
and O 0
maximum O 0
rate O 0
of O 0
rise O 0
of O 0
left O 0
ventricular O 0
pressure O 0
( O 0
LV O 0
dP O 0
/ O 0
dt O 0
max O 0
) O 0
had O 0
been O 0
reduced O 0
by O 0
about O 0
35 O 0
% O 0
and O 0
26 O 0
% O 0
of O 0
the O 0
respective O 0
controls O 0
were O 0
improved O 0
by O 0
denopamine B-Chemical 0
( O 0
10 O 0
- O 0
300 O 0
micrograms O 0
) O 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
manner O 0
. O 0

With O 0
100 O 0
micrograms O 0
denopamine B-Chemical 0
, O 0
almost O 0
complete O 0
restoration O 0
of O 0
cardiac O 0
performance O 0
was O 0
attained O 0
, O 0
associated O 0
with O 0
a O 0
slight O 0
increase O 0
in O 0
heart O 0
rate O 0
. O 0

No O 0
arrhythmias B-Disease 0
were O 0
induced O 0
by O 0
these O 0
doses O 0
of O 0
denopamine B-Chemical 0
. O 0

The O 0
results O 0
warrant O 0
clinical O 0
trials O 0
of O 0
denopamine B-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
cardiac B-Disease 0
failure I-Disease 0
. O 0

Clonazepam B-Chemical 0
monotherapy O 0
for O 0
epilepsy B-Disease 0
in O 0
childhood O 0
. O 0

Sixty O 0
patients O 0
( O 0
age O 0
- O 0
range O 0
one O 0
month O 0
to O 0
14 O 0
years O 0
) O 0
with O 0
other O 0
types O 0
of O 0
epilepsy B-Disease 0
than O 0
infantile B-Disease 0
spasms I-Disease 0
were O 0
treated O 0
with O 0
clonazepam B-Chemical 0
. O 0

Disappearance O 0
of O 0
seizures B-Disease 0
and O 0
normalization O 0
of O 0
abnormal O 0
EEG O 0
with O 0
disappearance O 0
of O 0
seizures B-Disease 0
were O 0
recognized O 0
in O 0
77 O 0
% O 0
and O 0
50 O 0
% O 0
, O 0
respectively O 0
. O 0

Seizures B-Disease 0
disappeared O 0
in O 0
71 O 0
% O 0
of O 0
the O 0
patients O 0
with O 0
generalized O 0
seizures B-Disease 0
and O 0
89 O 0
% O 0
of O 0
partial O 0
seizures B-Disease 0
. O 0

Improvement O 0
of O 0
abnormal O 0
EEG O 0
was O 0
noticed O 0
in O 0
76 O 0
% O 0
of O 0
diffuse O 0
paroxysms O 0
and O 0
in O 0
67 O 0
% O 0
of O 0
focal O 0
paroxysms O 0
. O 0

In O 0
excellent O 0
cases O 0
, O 0
mean O 0
effective O 0
dosages O 0
were O 0
0 O 0
. O 0
086 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
021 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
in O 0
infants O 0
and O 0
0 O 0
. O 0
057 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
022 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
in O 0
schoolchildren O 0
, O 0
this O 0
difference O 0
was O 0
statistically O 0
significant O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
005 O 0
) O 0
. O 0

The O 0
incidence O 0
of O 0
side O 0
effects O 0
such O 0
as O 0
drowsiness B-Disease 0
and O 0
ataxia B-Disease 0
was O 0
only O 0
5 O 0
% O 0
. O 0

Postmarketing O 0
study O 0
of O 0
timolol B-Chemical 0
- O 0
hydrochlorothiazide B-Chemical 0
antihypertensive O 0
therapy O 0
. O 0

A O 0
postmarketing O 0
surveillance O 0
study O 0
was O 0
conducted O 0
to O 0
determine O 0
the O 0
safety O 0
and O 0
efficacy O 0
of O 0
a O 0
fixed O 0
- O 0
ratio O 0
combination O 0
containing O 0
10 O 0
mg O 0
of O 0
timolol B-Chemical 0
maleate I-Chemical 0
and O 0
25 O 0
mg O 0
of O 0
hydrochlorothiazide B-Chemical 0
, O 0
administered O 0
twice O 0
daily O 0
for O 0
one O 0
month O 0
to O 0
hypertensive B-Disease 0
patients O 0
. O 0

Data O 0
on O 0
9 O 0
, O 0
037 O 0
patients O 0
were O 0
collected O 0
by O 0
1 O 0
, O 0
455 O 0
participating O 0
physicians O 0
. O 0

Mean O 0
systolic O 0
blood O 0
pressure O 0
decreased O 0
25 O 0
mmHg O 0
and O 0
mean O 0
diastolic O 0
blood O 0
pressure O 0
declined O 0
15 O 0
mmHg O 0
after O 0
one O 0
month O 0
of O 0
timolol B-Chemical 0
- O 0
hydrochlorothiazide B-Chemical 0
therapy O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
, O 0
both O 0
comparisons O 0
) O 0
. O 0

Age O 0
, O 0
race O 0
, O 0
and O 0
sex O 0
appeared O 0
to O 0
have O 0
no O 0
influence O 0
on O 0
the O 0
decrease O 0
in O 0
blood O 0
pressure O 0
. O 0

The O 0
antihypertensive O 0
effect O 0
of O 0
the O 0
drug O 0
was O 0
greater O 0
in O 0
patients O 0
with O 0
more O 0
severe O 0
hypertension B-Disease 0
. O 0

Overall O 0
, O 0
1 O 0
, O 0
453 O 0
patients O 0
experienced O 0
a O 0
total O 0
of O 0
2 O 0
, O 0
658 O 0
adverse O 0
events O 0
, O 0
the O 0
most O 0
common O 0
being O 0
fatigue B-Disease 0
, O 0
dizziness B-Disease 0
, O 0
and O 0
weakness B-Disease 0
. O 0

Treatment O 0
in O 0
590 O 0
patients O 0
was O 0
discontinued O 0
because O 0
of O 0
adverse O 0
events O 0
. O 0

Salicylate B-Chemical 0
nephropathy B-Disease 0
in O 0
the O 0
Gunn O 0
rat O 0
: O 0
potential O 0
role O 0
of O 0
prostaglandins B-Chemical 0
. O 0

We O 0
examined O 0
the O 0
potential O 0
role O 0
of O 0
prostaglandins B-Chemical 0
in O 0
the O 0
development O 0
of O 0
analgesic O 0
nephropathy B-Disease 0
in O 0
the O 0
Gunn O 0
strain O 0
of O 0
rat O 0
. O 0

The O 0
homozygous O 0
Gunn O 0
rats O 0
have O 0
unconjugated O 0
hyperbilirubinemia B-Disease 0
due O 0
to O 0
the O 0
absence O 0
of O 0
glucuronyl B-Chemical 0
transferase O 0
, O 0
leading O 0
to O 0
marked O 0
bilirubin B-Chemical 0
deposition O 0
in O 0
renal O 0
medulla O 0
and O 0
papilla O 0
. O 0

These O 0
rats O 0
are O 0
also O 0
highly O 0
susceptible O 0
to O 0
develop O 0
papillary B-Disease 0
necrosis I-Disease 0
with O 0
analgesic O 0
administration O 0
. O 0

We O 0
used O 0
homozygous O 0
( O 0
jj O 0
) O 0
and O 0
phenotypically O 0
normal O 0
heterozygous O 0
( O 0
jJ O 0
) O 0
animals O 0
. O 0

Four O 0
groups O 0
of O 0
rats O 0
( O 0
n O 0
= O 0
7 O 0
) O 0
were O 0
studied O 0
: O 0
jj O 0
and O 0
jJ O 0
rats O 0
treated O 0
either O 0
with O 0
aspirin B-Chemical 0
300 O 0
mg O 0
/ O 0
kg O 0
every O 0
other O 0
day O 0
or O 0
sham O 0
- O 0
treated O 0
. O 0

After O 0
one O 0
week O 0
, O 0
slices O 0
of O 0
cortex O 0
, O 0
outer O 0
and O 0
inner O 0
medulla O 0
from O 0
one O 0
kidney O 0
were O 0
incubated O 0
in O 0
buffer O 0
and O 0
prostaglandin B-Chemical 0
synthesis O 0
was O 0
determined O 0
by O 0
radioimmunoassay O 0
. O 0

The O 0
other O 0
kidney O 0
was O 0
examined O 0
histologically O 0
. O 0

A O 0
marked O 0
corticomedullary O 0
gradient O 0
of O 0
prostaglandin B-Chemical 0
synthesis O 0
was O 0
observed O 0
in O 0
all O 0
groups O 0
. O 0

PGE2 B-Chemical 0
synthesis O 0
was O 0
significantly O 0
higher O 0
in O 0
outer O 0
medulla O 0
, O 0
but O 0
not O 0
cortex O 0
or O 0
inner O 0
medulla O 0
, O 0
of O 0
jj O 0
( O 0
38 O 0
+ O 0
/ O 0
- O 0
6 O 0
ng O 0
/ O 0
mg O 0
prot O 0
) O 0
than O 0
jJ O 0
rats O 0
( O 0
15 O 0
+ O 0
/ O 0
- O 0
3 O 0
) O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Aspirin B-Chemical 0
treatment O 0
reduced O 0
PGE2 B-Chemical 0
synthesis O 0
in O 0
all O 0
regions O 0
, O 0
but O 0
outer O 0
medullary O 0
PGE2 B-Chemical 0
remained O 0
higher O 0
in O 0
jj O 0
( O 0
18 O 0
+ O 0
/ O 0
- O 0
3 O 0
) O 0
than O 0
jJ O 0
rats O 0
( O 0
9 O 0
+ O 0
/ O 0
- O 0
2 O 0
) O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

PGF2 B-Chemical 0
alpha I-Chemical 0
was O 0
also O 0
significantly O 0
higher O 0
in O 0
the O 0
outer O 0
medulla O 0
of O 0
jj O 0
rats O 0
with O 0
and O 0
without O 0
aspirin B-Chemical 0
administration O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

The O 0
changes O 0
in O 0
renal O 0
prostaglandin B-Chemical 0
synthesis O 0
were O 0
accompanied O 0
by O 0
evidence O 0
of O 0
renal B-Disease 0
damage I-Disease 0
in O 0
aspirin B-Chemical 0
- O 0
treated O 0
jj O 0
but O 0
not O 0
jJ O 0
rats O 0
as O 0
evidenced O 0
by O 0
: O 0
increased O 0
incidence O 0
and O 0
severity O 0
of O 0
hematuria B-Disease 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
; O 0
increased O 0
serum O 0
creatinine B-Chemical 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
; O 0
and O 0
increase O 0
in O 0
outer O 0
medullary O 0
histopathologic O 0
lesions O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
005 O 0
compared O 0
to O 0
either O 0
sham O 0
- O 0
treated O 0
jj O 0
or O 0
aspirin B-Chemical 0
- O 0
treated O 0
jJ O 0
) O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
enhanced O 0
prostaglandin B-Chemical 0
synthesis O 0
contributes O 0
to O 0
maintenance O 0
of O 0
renal O 0
function O 0
and O 0
morphological O 0
integrity O 0
, O 0
and O 0
that O 0
inhibition O 0
of O 0
prostaglandin B-Chemical 0
synthesis O 0
may O 0
lead O 0
to O 0
pathological B-Disease 0
renal I-Disease 0
medullary I-Disease 0
lesions I-Disease 0
and O 0
deterioration B-Disease 0
of I-Disease 0
renal I-Disease 0
function I-Disease 0
. O 0

Prophylactic O 0
lidocaine B-Chemical 0
in O 0
the O 0
early O 0
phase O 0
of O 0
suspected O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

Four O 0
hundred O 0
two O 0
patients O 0
with O 0
suspected O 0
myocardial B-Disease 0
infarction I-Disease 0
seen O 0
within O 0
6 O 0
hours O 0
of O 0
the O 0
onset O 0
of O 0
symptoms O 0
entered O 0
a O 0
double O 0
- O 0
blind O 0
randomized O 0
trial O 0
of O 0
lidocaine B-Chemical 0
vs O 0
placebo O 0
. O 0

During O 0
the O 0
1 O 0
hour O 0
after O 0
administration O 0
of O 0
the O 0
drug O 0
the O 0
incidence O 0
of O 0
ventricular B-Disease 0
fibrillation I-Disease 0
or O 0
sustained O 0
ventricular B-Disease 0
tachycardia I-Disease 0
among O 0
the O 0
204 O 0
patients O 0
with O 0
acute O 0
myocardial B-Disease 0
infarction I-Disease 0
was O 0
low O 0
, O 0
1 O 0
. O 0
5 O 0
% O 0
. O 0

Lidocaine B-Chemical 0
, O 0
given O 0
in O 0
a O 0
300 O 0
mg O 0
dose O 0
intramuscularly O 0
followed O 0
by O 0
100 O 0
mg O 0
intravenously O 0
, O 0
did O 0
not O 0
prevent O 0
sustained O 0
ventricular B-Disease 0
tachycardia I-Disease 0
, O 0
although O 0
there O 0
was O 0
a O 0
significant O 0
reduction O 0
in O 0
the O 0
number O 0
of O 0
patients O 0
with O 0
warning O 0
arrhythmias B-Disease 0
between O 0
15 O 0
and O 0
45 O 0
minutes O 0
after O 0
the O 0
administration O 0
of O 0
lidocaine B-Chemical 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

The O 0
average O 0
plasma O 0
lidocaine B-Chemical 0
level O 0
10 O 0
minutes O 0
after O 0
administration O 0
for O 0
patients O 0
without O 0
a O 0
myocardial B-Disease 0
infarction I-Disease 0
was O 0
significantly O 0
higher O 0
than O 0
that O 0
for O 0
patients O 0
with O 0
an O 0
acute O 0
infarction B-Disease 0
. O 0

The O 0
mean O 0
plasma O 0
lidocaine B-Chemical 0
level O 0
of O 0
patients O 0
on O 0
beta O 0
- O 0
blocking O 0
agents O 0
was O 0
no O 0
different O 0
from O 0
that O 0
in O 0
patients O 0
not O 0
on O 0
beta O 0
blocking O 0
agents O 0
. O 0

During O 0
the O 0
1 O 0
- O 0
hour O 0
study O 0
period O 0
, O 0
the O 0
incidence O 0
of O 0
central O 0
nervous O 0
system O 0
side O 0
effects O 0
was O 0
significantly O 0
greater O 0
in O 0
the O 0
lidocaine B-Chemical 0
group O 0
, O 0
hypotension B-Disease 0
occurred O 0
in O 0
11 O 0
patients O 0
, O 0
nine O 0
of O 0
whom O 0
had O 0
received O 0
lidocaine B-Chemical 0
, O 0
and O 0
four O 0
patients O 0
died O 0
from O 0
asystole B-Disease 0
, O 0
three O 0
of O 0
whom O 0
had O 0
had O 0
lidocaine B-Chemical 0
. O 0

We O 0
cannot O 0
advocate O 0
the O 0
administration O 0
of O 0
lidocaine B-Chemical 0
prophylactically O 0
in O 0
the O 0
early O 0
hours O 0
of O 0
suspected O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

Evidence O 0
for O 0
a O 0
cholinergic O 0
role O 0
in O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
. O 0

Experiments O 0
in O 0
mice O 0
tested O 0
previous O 0
evidence O 0
that O 0
activation O 0
of O 0
cholinergic O 0
systems O 0
promotes O 0
catalepsy B-Disease 0
and O 0
that O 0
cholinergic O 0
mechanisms O 0
need O 0
to O 0
be O 0
intact O 0
for O 0
full O 0
expression O 0
of O 0
neuroleptic B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
. O 0

Large O 0
doses O 0
of O 0
the O 0
cholinomimetic O 0
, O 0
pilocarpine B-Chemical 0
, O 0
could O 0
induce O 0
catalepsy B-Disease 0
when O 0
peripheral O 0
cholinergic O 0
receptors O 0
were O 0
blocked O 0
. O 0

Low O 0
doses O 0
of O 0
pilocarpine B-Chemical 0
caused O 0
a O 0
pronounced O 0
enhancement O 0
of O 0
the O 0
catalepsy B-Disease 0
that O 0
was O 0
induced O 0
by O 0
the O 0
dopaminergic O 0
blocker O 0
, O 0
haloperidol B-Chemical 0
. O 0

A O 0
muscarinic O 0
receptor O 0
blocker O 0
, O 0
atropine B-Chemical 0
, O 0
disrupted O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
. O 0

Intracranial O 0
injection O 0
of O 0
an O 0
acetylcholine B-Chemical 0
- O 0
synthesis O 0
inhibitor O 0
, O 0
hemicholinium B-Chemical 0
, O 0
prevented O 0
the O 0
catalepsy B-Disease 0
that O 0
is O 0
usually O 0
induced O 0
by O 0
haloperidol B-Chemical 0
. O 0

These O 0
findings O 0
suggest O 0
the O 0
hypothesis O 0
that O 0
the O 0
catalepsy B-Disease 0
that O 0
is O 0
produced O 0
by O 0
neuroleptics B-Chemical 0
such O 0
as O 0
haloperidol B-Chemical 0
is O 0
actually O 0
mediated O 0
by O 0
intrinsic O 0
central O 0
cholinergic O 0
systems O 0
. O 0

Alternatively O 0
, O 0
activation O 0
of O 0
central O 0
cholinergic O 0
systems O 0
could O 0
promote O 0
catalepsy B-Disease 0
by O 0
suppression O 0
of O 0
dopaminergic O 0
systems O 0
. O 0

Cardiovascular B-Disease 0
dysfunction I-Disease 0
and O 0
hypersensitivity B-Disease 0
to O 0
sodium B-Chemical 0
pentobarbital I-Chemical 0
induced O 0
by O 0
chronic O 0
barium B-Chemical 0
chloride I-Chemical 0
ingestion O 0
. O 0

Barium B-Chemical 0
- O 0
supplemented O 0
Long O 0
- O 0
Evans O 0
hooded O 0
rats O 0
were O 0
characterized O 0
by O 0
a O 0
persistent O 0
hypertension B-Disease 0
that O 0
was O 0
evident O 0
after O 0
1 O 0
month O 0
of O 0
barium B-Chemical 0
( O 0
100 O 0
micrograms O 0
/ O 0
ml O 0
mineral O 0
fortified O 0
water O 0
) O 0
treatment O 0
. O 0

Analysis O 0
of O 0
in O 0
vivo O 0
myocardial O 0
excitability O 0
, O 0
contractility O 0
, O 0
and O 0
metabolic O 0
characteristics O 0
at O 0
16 O 0
months O 0
revealed O 0
other O 0
significant O 0
barium B-Chemical 0
- O 0
induced O 0
disturbances B-Disease 0
within I-Disease 0
the I-Disease 0
cardiovascular I-Disease 0
system I-Disease 0
. O 0

The O 0
most O 0
distinctive O 0
aspect O 0
of O 0
the O 0
barium B-Chemical 0
effect O 0
was O 0
a O 0
demonstrated O 0
hypersensitivity B-Disease 0
of O 0
the O 0
cardiovascular O 0
system O 0
to O 0
sodium B-Chemical 0
pentobarbital I-Chemical 0
. O 0

Under O 0
barbiturate B-Chemical 0
anesthesia O 0
, O 0
virtually O 0
all O 0
of O 0
the O 0
myocardial O 0
contractile O 0
indices O 0
were O 0
depressed O 0
significantly O 0
in O 0
barium B-Chemical 0
- O 0
exposed O 0
rats O 0
relative O 0
to O 0
the O 0
corresponding O 0
control O 0
- O 0
fed O 0
rats O 0
. O 0

The O 0
lack O 0
of O 0
a O 0
similar O 0
response O 0
to O 0
ketamine B-Chemical 0
and O 0
xylazine B-Chemical 0
anesthesia O 0
revealed O 0
that O 0
the O 0
cardiovascular O 0
actions O 0
of O 0
sodium B-Chemical 0
pentobarbital I-Chemical 0
in O 0
barium B-Chemical 0
- O 0
treated O 0
rats O 0
were O 0
linked O 0
specifically O 0
to O 0
this O 0
anesthetic O 0
, O 0
and O 0
were O 0
not O 0
representative O 0
of O 0
a O 0
generalized O 0
anesthetic O 0
response O 0
. O 0

Other O 0
myocardial O 0
pathophysiologic O 0
and O 0
metabolic O 0
changes O 0
induced O 0
by O 0
barium B-Chemical 0
were O 0
manifest O 0
, O 0
irrespective O 0
of O 0
the O 0
anesthetic O 0
employed O 0
. O 0

The O 0
contractile O 0
element O 0
shortening O 0
velocity O 0
of O 0
the O 0
cardiac O 0
muscle O 0
fibers O 0
was O 0
significantly O 0
slower O 0
in O 0
both O 0
groups O 0
of O 0
barium B-Chemical 0
- O 0
treated O 0
rats O 0
relative O 0
to O 0
the O 0
control O 0
groups O 0
, O 0
irrespective O 0
of O 0
the O 0
anesthetic O 0
regimen O 0
. O 0

Similarly O 0
, O 0
significant O 0
disturbances O 0
in O 0
myocardial O 0
energy O 0
metabolism O 0
were O 0
detected O 0
in O 0
the O 0
barium B-Chemical 0
- O 0
exposed O 0
rats O 0
which O 0
were O 0
consistent O 0
with O 0
the O 0
reduced O 0
contractile O 0
element O 0
shortening O 0
velocity O 0
. O 0

In O 0
addition O 0
, O 0
the O 0
excitability O 0
of O 0
the O 0
cardiac O 0
conduction O 0
system O 0
was O 0
depressed O 0
preferentially O 0
in O 0
the O 0
atrioventricular O 0
nodal O 0
region O 0
of O 0
hearts O 0
from O 0
barium B-Chemical 0
- O 0
exposed O 0
rats O 0
. O 0

Overall O 0
, O 0
the O 0
altered O 0
cardiac O 0
contractility O 0
and O 0
excitability O 0
characteristics O 0
, O 0
the O 0
myocardial O 0
metabolic B-Disease 0
disturbances I-Disease 0
, O 0
and O 0
the O 0
hypersensitivity B-Disease 0
of O 0
the O 0
cardiovascular O 0
system O 0
to O 0
sodium B-Chemical 0
pentobarbital I-Chemical 0
suggest O 0
the O 0
existence O 0
of O 0
a O 0
heretofore O 0
undescribed O 0
cardiomyopathic B-Disease 0
disorder I-Disease 0
induced O 0
by O 0
chronic O 0
barium B-Chemical 0
exposure O 0
. O 0

These O 0
experimental O 0
findings O 0
represent O 0
the O 0
first O 0
indication O 0
that O 0
life O 0
- O 0
long O 0
barium B-Chemical 0
ingestion O 0
may O 0
have O 0
significant O 0
adverse O 0
effects O 0
on O 0
the O 0
mammalian O 0
cardiovascular O 0
system O 0
. O 0

Propranolol B-Chemical 0
antagonism O 0
of O 0
phenylpropanolamine B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
. O 0

Phenylpropanolamine B-Chemical 0
( O 0
PPA B-Chemical 0
) O 0
overdose B-Disease 0
can O 0
cause O 0
severe O 0
hypertension B-Disease 0
, O 0
intracerebral B-Disease 0
hemorrhage I-Disease 0
, O 0
and O 0
death O 0
. O 0

We O 0
studied O 0
the O 0
efficacy O 0
and O 0
safety O 0
of O 0
propranolol B-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
PPA B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
. O 0

Subjects O 0
received O 0
propranolol B-Chemical 0
either O 0
by O 0
mouth O 0
for O 0
48 O 0
hours O 0
before O 0
PPA B-Chemical 0
or O 0
as O 0
a O 0
rapid O 0
intravenous O 0
infusion O 0
after O 0
PPA B-Chemical 0
. O 0

PPA B-Chemical 0
, O 0
75 O 0
mg O 0
alone O 0
, O 0
increased O 0
blood O 0
pressure O 0
( O 0
31 O 0
+ O 0
/ O 0
- O 0
14 O 0
mm O 0
Hg O 0
systolic O 0
, O 0
20 O 0
+ O 0
/ O 0
- O 0
5 O 0
mm O 0
Hg O 0
diastolic O 0
) O 0
, O 0
and O 0
propranolol B-Chemical 0
pretreatment O 0
antagonized O 0
this O 0
increase O 0
( O 0
12 O 0
+ O 0
/ O 0
- O 0
10 O 0
mm O 0
Hg O 0
systolic O 0
, O 0
10 O 0
+ O 0
/ O 0
- O 0
7 O 0
mm O 0
Hg O 0
diastolic O 0
) O 0
. O 0

Intravenous O 0
propranolol B-Chemical 0
after O 0
PPA B-Chemical 0
also O 0
decreased O 0
blood O 0
pressure O 0
. O 0

Left O 0
ventricular O 0
function O 0
( O 0
assessed O 0
by O 0
echocardiography O 0
) O 0
showed O 0
that O 0
PPA B-Chemical 0
increased O 0
the O 0
stroke B-Disease 0
volume O 0
30 O 0
% O 0
( O 0
from O 0
62 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
20 O 0
. O 0
9 O 0
to O 0
80 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
22 O 0
. O 0
4 O 0
ml O 0
) O 0
, O 0
the O 0
ejection O 0
fraction O 0
9 O 0
% O 0
( O 0
from O 0
64 O 0
% O 0
+ O 0
/ O 0
- O 0
10 O 0
% O 0
to O 0
70 O 0
% O 0
+ O 0
/ O 0
- O 0
7 O 0
% O 0
) O 0
, O 0
and O 0
cardiac O 0
output O 0
14 O 0
% O 0
( O 0
from O 0
3 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
6 O 0
to O 0
4 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
0 O 0
L O 0
/ O 0
min O 0
) O 0
. O 0

Intravenous O 0
propranolol B-Chemical 0
reversed O 0
these O 0
effects O 0
. O 0

Systemic O 0
vascular O 0
resistance O 0
was O 0
increased O 0
by O 0
PPA B-Chemical 0
28 O 0
% O 0
( O 0
from O 0
1710 O 0
+ O 0
/ O 0
- O 0
200 O 0
to O 0
2190 O 0
+ O 0
/ O 0
- O 0
700 O 0
dyne O 0
X O 0
sec O 0
/ O 0
cm5 O 0
) O 0
and O 0
was O 0
further O 0
increased O 0
by O 0
propranolol B-Chemical 0
22 O 0
% O 0
( O 0
to O 0
2660 O 0
+ O 0
/ O 0
- O 0
1200 O 0
dyne O 0
X O 0
sec O 0
/ O 0
cm5 O 0
) O 0
. O 0

We O 0
conclude O 0
that O 0
PPA B-Chemical 0
increases O 0
blood O 0
pressure O 0
by O 0
increasing O 0
systemic O 0
vascular O 0
resistance O 0
and O 0
cardiac O 0
output O 0
, O 0
and O 0
that O 0
propranolol B-Chemical 0
antagonizes O 0
this O 0
increase O 0
by O 0
reversing O 0
the O 0
effect O 0
of O 0
PPA B-Chemical 0
on O 0
cardiac O 0
output O 0
. O 0

That O 0
propranolol B-Chemical 0
antagonizes O 0
the O 0
pressor O 0
effect O 0
of O 0
PPA B-Chemical 0
is O 0
in O 0
contrast O 0
to O 0
the O 0
interaction O 0
in O 0
which O 0
propranolol B-Chemical 0
enhances O 0
the O 0
pressor O 0
effect O 0
of O 0
norepinephrine B-Chemical 0
. O 0

This O 0
is O 0
probably O 0
because O 0
PPA B-Chemical 0
has O 0
less O 0
beta O 0
2 O 0
activity O 0
than O 0
does O 0
norepinephrine B-Chemical 0
. O 0

Mesangial O 0
function O 0
and O 0
glomerular B-Disease 0
sclerosis I-Disease 0
in O 0
rats O 0
with O 0
aminonucleoside B-Chemical 0
nephrosis B-Disease 0
. O 0

The O 0
possible O 0
relationship O 0
between O 0
mesangial B-Disease 0
dysfunction I-Disease 0
and O 0
development O 0
of O 0
glomerular B-Disease 0
sclerosis I-Disease 0
was O 0
studied O 0
in O 0
the O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
( O 0
PAN B-Chemical 0
) O 0
model O 0
. O 0

Five O 0
male O 0
Wistar O 0
rats O 0
received O 0
repeated O 0
subcutaneous O 0
PAN B-Chemical 0
injections O 0
; O 0
five O 0
controls O 0
received O 0
saline O 0
only O 0
. O 0

After O 0
4 O 0
weeks O 0
the O 0
PAN B-Chemical 0
rats O 0
were O 0
severely O 0
proteinuric B-Disease 0
( O 0
190 O 0
+ O 0
/ O 0
- O 0
80 O 0
mg O 0
/ O 0
24 O 0
hr O 0
) O 0
, O 0
and O 0
all O 0
rats O 0
were O 0
given O 0
colloidal O 0
carbon B-Chemical 0
( O 0
CC O 0
) O 0
intravenously O 0
. O 0

At O 0
5 O 0
months O 0
glomerular B-Disease 0
sclerosis I-Disease 0
was O 0
found O 0
in O 0
7 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
4 O 0
% O 0
of O 0
the O 0
glomeruli O 0
of O 0
PAN B-Chemical 0
rats O 0
; O 0
glomeruli O 0
of O 0
the O 0
controls O 0
were O 0
normal O 0
. O 0

Glomeruli O 0
of O 0
PAN B-Chemical 0
rats O 0
contained O 0
significantly O 0
more O 0
CC O 0
than O 0
glomeruli O 0
of O 0
controls O 0
. O 0

Glomeruli O 0
with O 0
sclerosis B-Disease 0
contained O 0
significantly O 0
more O 0
CC O 0
than O 0
non O 0
- O 0
sclerotic O 0
glomeruli O 0
in O 0
the O 0
same O 0
kidneys O 0
. O 0

CC O 0
was O 0
preferentially O 0
localized O 0
within O 0
the O 0
sclerotic O 0
areas O 0
of O 0
the O 0
affected O 0
glomeruli O 0
. O 0

Since O 0
mesangial O 0
CC O 0
clearance O 0
from O 0
the O 0
mesangium O 0
did O 0
not O 0
change O 0
during O 0
chronic O 0
PAN B-Chemical 0
treatment O 0
, O 0
we O 0
conclude O 0
that O 0
this O 0
preferential O 0
CC O 0
localization O 0
within O 0
the O 0
lesions O 0
is O 0
caused O 0
by O 0
an O 0
increased O 0
CC O 0
uptake O 0
shortly O 0
after O 0
injection O 0
in O 0
apparent O 0
vulnerable O 0
areas O 0
where O 0
sclerosis B-Disease 0
will O 0
develop O 0
subsequently O 0
. O 0

Cluster O 0
analysis O 0
showed O 0
a O 0
random O 0
distribution O 0
of O 0
lesions O 0
in O 0
the O 0
PAN B-Chemical 0
glomeruli O 0
in O 0
concordance O 0
with O 0
the O 0
random O 0
localization O 0
of O 0
mesangial O 0
areas O 0
with O 0
dysfunction O 0
in O 0
this O 0
model O 0
. O 0

Similar O 0
to O 0
the O 0
remnant O 0
kidney O 0
model O 0
in O 0
PAN B-Chemical 0
nephrosis B-Disease 0
the O 0
development O 0
of O 0
glomerular B-Disease 0
sclerosis I-Disease 0
may O 0
be O 0
related O 0
to O 0
" O 0
mesangial O 0
overloading O 0
. O 0
" O 0

Relationship O 0
between O 0
nicotine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
and O 0
hippocampal O 0
nicotinic O 0
receptors O 0
. O 0

A O 0
controversy O 0
has O 0
existed O 0
for O 0
several O 0
years O 0
concerning O 0
the O 0
physiological O 0
relevance O 0
of O 0
the O 0
nicotinic O 0
receptor O 0
measured O 0
by O 0
alpha O 0
- O 0
bungarotoxin O 0
binding O 0
. O 0

Using O 0
mice O 0
derived O 0
from O 0
a O 0
classical O 0
F2 O 0
and O 0
backcross O 0
genetic O 0
design O 0
, O 0
a O 0
relationship O 0
between O 0
nicotine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
and O 0
alpha O 0
- O 0
bungarotoxin O 0
nicotinic O 0
receptor O 0
concentration O 0
was O 0
found O 0
. O 0

Mice O 0
sensitive O 0
to O 0
the O 0
convulsant O 0
effects O 0
of O 0
nicotine B-Chemical 0
had O 0
greater O 0
alpha O 0
- O 0
bungarotoxin O 0
binding O 0
in O 0
the O 0
hippocampus O 0
than O 0
seizure B-Disease 0
insensitive O 0
mice O 0
. O 0

The O 0
binding O 0
sites O 0
from O 0
seizure B-Disease 0
sensitive O 0
and O 0
resistant O 0
mice O 0
were O 0
equally O 0
affected O 0
by O 0
treatment O 0
with O 0
dithiothreitol B-Chemical 0
, O 0
trypsin O 0
or O 0
heat O 0
. O 0

Thus O 0
it O 0
appears O 0
that O 0
the O 0
difference O 0
between O 0
seizure B-Disease 0
sensitive O 0
and O 0
insensitive O 0
animals O 0
may O 0
be O 0
due O 0
to O 0
a O 0
difference O 0
in O 0
hippocampal O 0
nicotinic O 0
receptor O 0
concentration O 0
as O 0
measured O 0
with O 0
alpha O 0
- O 0
bungarotoxin O 0
binding O 0
. O 0

The O 0
role O 0
of O 0
p B-Chemical 0
- I-Chemical 0
aminophenol I-Chemical 0
in O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
: O 0
effect O 0
of O 0
bis B-Chemical 0
( I-Chemical 0
p I-Chemical 0
- I-Chemical 0
nitrophenyl I-Chemical 0
) I-Chemical 0
phosphate I-Chemical 0
on O 0
acetaminophen B-Chemical 0
and O 0
p B-Chemical 0
- I-Chemical 0
aminophenol I-Chemical 0
nephrotoxicity B-Disease 0
and O 0
metabolism O 0
in O 0
Fischer O 0
344 O 0
rats O 0
. O 0

Acetaminophen B-Chemical 0
( O 0
APAP B-Chemical 0
) O 0
produces O 0
proximal O 0
tubular B-Disease 0
necrosis I-Disease 0
in O 0
Fischer O 0
344 O 0
( O 0
F344 O 0
) O 0
rats O 0
. O 0

Recently O 0
, O 0
p B-Chemical 0
- I-Chemical 0
aminophenol I-Chemical 0
( O 0
PAP B-Chemical 0
) O 0
, O 0
a O 0
known O 0
potent O 0
nephrotoxicant O 0
, O 0
was O 0
identified O 0
as O 0
a O 0
metabolite O 0
of O 0
APAP B-Chemical 0
in O 0
F344 O 0
rats O 0
. O 0

The O 0
purpose O 0
of O 0
this O 0
study O 0
was O 0
to O 0
determine O 0
if O 0
PAP B-Chemical 0
formation O 0
is O 0
a O 0
requisite O 0
step O 0
in O 0
APAP B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
. O 0

Therefore O 0
, O 0
the O 0
effect O 0
of O 0
bis B-Chemical 0
( I-Chemical 0
p I-Chemical 0
- I-Chemical 0
nitrophenyl I-Chemical 0
) I-Chemical 0
phosphate I-Chemical 0
( O 0
BNPP B-Chemical 0
) O 0
, O 0
an O 0
acylamidase O 0
inhibitor O 0
, O 0
on O 0
APAP B-Chemical 0
and O 0
PAP B-Chemical 0
nephrotoxicity B-Disease 0
and O 0
metabolism O 0
was O 0
determined O 0
. O 0

BNPP B-Chemical 0
( O 0
1 O 0
to O 0
8 O 0
mM O 0
) O 0
reduced O 0
APAP B-Chemical 0
deacetylation O 0
and O 0
covalent O 0
binding O 0
in O 0
F344 O 0
renal O 0
cortical O 0
homogenates O 0
in O 0
a O 0
concentration O 0
- O 0
dependent O 0
manner O 0
. O 0

Pretreatment O 0
of O 0
animals O 0
with O 0
BNPP B-Chemical 0
prior O 0
to O 0
APAP B-Chemical 0
or O 0
PAP B-Chemical 0
administration O 0
resulted O 0
in O 0
marked O 0
reduction O 0
of O 0
APAP B-Chemical 0
( O 0
900 O 0
mg O 0
/ O 0
kg O 0
) O 0
nephrotoxicity B-Disease 0
but O 0
not O 0
PAP B-Chemical 0
nephrotoxicity B-Disease 0
. O 0

This O 0
result O 0
was O 0
not O 0
due O 0
to O 0
altered O 0
disposition O 0
of O 0
either O 0
APAP B-Chemical 0
or O 0
acetylated O 0
metabolites O 0
in O 0
plasma O 0
or O 0
renal O 0
cortical O 0
and O 0
hepatic O 0
tissue O 0
. O 0

Rather O 0
, O 0
BNPP B-Chemical 0
pretreatment O 0
reduced O 0
the O 0
fraction O 0
of O 0
APAP B-Chemical 0
excreted O 0
as O 0
PAP B-Chemical 0
by O 0
64 O 0
and O 0
75 O 0
% O 0
after O 0
APAP B-Chemical 0
doses O 0
of O 0
750 O 0
and O 0
900 O 0
mg O 0
/ O 0
kg O 0
. O 0

BNPP B-Chemical 0
did O 0
not O 0
alter O 0
the O 0
excretion O 0
of O 0
APAP B-Chemical 0
or O 0
any O 0
of O 0
its O 0
non O 0
- O 0
deacetylated O 0
metabolites O 0
nor O 0
did O 0
BNPP B-Chemical 0
alter O 0
excretion O 0
of O 0
PAP B-Chemical 0
or O 0
its O 0
metabolites O 0
after O 0
PAP B-Chemical 0
doses O 0
of O 0
150 O 0
and O 0
300 O 0
mg O 0
/ O 0
kg O 0
. O 0

Therefore O 0
, O 0
the O 0
BNPP B-Chemical 0
- O 0
induced O 0
reduction O 0
in O 0
APAP B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
appears O 0
to O 0
be O 0
due O 0
to O 0
inhibition O 0
of O 0
APAP B-Chemical 0
deacetylation O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
PAP B-Chemical 0
formation O 0
, O 0
in O 0
vivo O 0
, O 0
accounts O 0
, O 0
at O 0
least O 0
in O 0
part O 0
, O 0
for O 0
APAP B-Chemical 0
- O 0
induced O 0
renal B-Disease 0
tubular I-Disease 0
necrosis I-Disease 0
. O 0

Morphine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
in O 0
newborn O 0
infants O 0
. O 0

Two O 0
neonates O 0
suffered O 0
from O 0
generalized O 0
seizures B-Disease 0
during O 0
the O 0
course O 0
of O 0
intravenous O 0
morphine B-Chemical 0
sulfate I-Chemical 0
for O 0
post O 0
- O 0
operative O 0
analgesia O 0
. O 0

They O 0
received O 0
morphine B-Chemical 0
in O 0
doses O 0
of O 0
32 O 0
micrograms O 0
/ O 0
kg O 0
/ O 0
hr O 0
and O 0
40 O 0
micrograms O 0
/ O 0
kg O 0
/ O 0
hr O 0
larger O 0
than O 0
a O 0
group O 0
of O 0
10 O 0
neonates O 0
who O 0
received O 0
6 O 0
- O 0
24 O 0
micrograms O 0
/ O 0
kg O 0
/ O 0
hr O 0
and O 0
had O 0
no O 0
seizures B-Disease 0
. O 0

Plasma O 0
concentrations O 0
of O 0
morphine B-Chemical 0
in O 0
these O 0
neonates O 0
was O 0
excessive O 0
( O 0
60 O 0
and O 0
90 O 0
mg O 0
/ O 0
ml O 0
) O 0
. O 0

Other O 0
known O 0
reasons O 0
for O 0
seizures B-Disease 0
were O 0
ruled O 0
out O 0
and O 0
the O 0
convulsions B-Disease 0
stopped O 0
a O 0
few O 0
hours O 0
after O 0
cessation O 0
of O 0
morphine B-Chemical 0
and O 0
did O 0
not O 0
reoccur O 0
in O 0
the O 0
subsequent O 0
8 O 0
months O 0
. O 0

It O 0
is O 0
suggested O 0
that O 0
post O 0
- O 0
operative O 0
intravenous O 0
morphine B-Chemical 0
should O 0
not O 0
exceed O 0
20 O 0
micrograms O 0
/ O 0
kg O 0
/ O 0
ml O 0
in O 0
neonates O 0
. O 0

Indomethacin B-Chemical 0
induced O 0
hypotension B-Disease 0
in O 0
sodium B-Chemical 0
and O 0
volume O 0
depleted O 0
rats O 0
. O 0

After O 0
a O 0
single O 0
oral O 0
dose O 0
of O 0
4 O 0
mg O 0
/ O 0
kg O 0
indomethacin B-Chemical 0
( O 0
IDM B-Chemical 0
) O 0
to O 0
sodium B-Chemical 0
and O 0
volume O 0
depleted O 0
rats O 0
plasma O 0
renin O 0
activity O 0
( O 0
PRA O 0
) O 0
and O 0
systolic O 0
blood O 0
pressure O 0
fell O 0
significantly O 0
within O 0
four O 0
hours O 0
. O 0

In O 0
sodium B-Chemical 0
repleted O 0
animals O 0
indomethacin B-Chemical 0
did O 0
not O 0
change O 0
systolic O 0
blood O 0
pressure O 0
( O 0
BP O 0
) O 0
although O 0
plasma O 0
renin O 0
activity O 0
was O 0
decreased O 0
. O 0

Thus O 0
, O 0
indomethacin B-Chemical 0
by O 0
inhibition O 0
of O 0
prostaglandin B-Chemical 0
synthesis O 0
may O 0
diminish O 0
the O 0
blood O 0
pressure O 0
maintaining O 0
effect O 0
of O 0
the O 0
stimulated O 0
renin O 0
- O 0
angiotensin B-Chemical 0
system O 0
in O 0
sodium B-Chemical 0
and O 0
volume O 0
depletion O 0
. O 0

On O 0
the O 0
antiarrhythmic O 0
activity O 0
of O 0
one O 0
N O 0
- O 0
substituted O 0
piperazine B-Chemical 0
derivative O 0
of O 0
trans B-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
amino I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
hydroxy I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
2 I-Chemical 0
, I-Chemical 0
3 I-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
tetrahydroanaphthalene I-Chemical 0
. O 0

The O 0
antiarrhythmic O 0
activity O 0
of O 0
the O 0
compound O 0
N B-Chemical 0
- I-Chemical 0
( I-Chemical 0
trans I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
hydroxy I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
2 I-Chemical 0
, I-Chemical 0
3 I-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
tetrahydro I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
naphthyl I-Chemical 0
) I-Chemical 0
- I-Chemical 0
N I-Chemical 0
- I-Chemical 0
( I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
oxo I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
phenyl I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
methylpropyl I-Chemical 0
) I-Chemical 0
- I-Chemical 0
piperazine I-Chemical 0
hydrochloride I-Chemical 0
, O 0
referred O 0
to O 0
as O 0
P11 B-Chemical 0
, O 0
is O 0
studied O 0
on O 0
anaesthesized O 0
cats O 0
and O 0
Wistar O 0
albino O 0
rats O 0
, O 0
as O 0
well O 0
as O 0
on O 0
non O 0
- O 0
anaesthesized O 0
rabbits O 0
. O 0

Four O 0
types O 0
of O 0
experimental O 0
arrhythmia B-Disease 0
are O 0
used O 0
- O 0
- O 0
with O 0
BaCl2 B-Chemical 0
, O 0
with O 0
chloroform B-Chemical 0
- O 0
adrenaline B-Chemical 0
, O 0
with O 0
strophantine B-Chemical 0
G I-Chemical 0
and O 0
with O 0
aconitine B-Chemical 0
. O 0

The O 0
compound O 0
P11 B-Chemical 0
is O 0
introduced O 0
in O 0
doses O 0
of O 0
0 O 0
. O 0
25 O 0
and O 0
0 O 0
. O 0
50 O 0
mg O 0
/ O 0
kg O 0
intravenously O 0
and O 0
10 O 0
mg O 0
/ O 0
kg O 0
orally O 0
. O 0

The O 0
compound O 0
manifests O 0
antiarrhythmic O 0
activity O 0
in O 0
all O 0
models O 0
of O 0
experimental O 0
arrhythmia B-Disease 0
used O 0
, O 0
causing O 0
greatest O 0
inhibition O 0
on O 0
the O 0
arrhythmia B-Disease 0
induced O 0
by O 0
chloroform B-Chemical 0
- O 0
adrenaline B-Chemical 0
( O 0
in O 0
90 O 0
per O 0
cent O 0
) O 0
and O 0
with O 0
BaCl2 B-Chemical 0
( O 0
in O 0
84 O 0
per O 0
cent O 0
) O 0
. O 0

The O 0
results O 0
obtained O 0
are O 0
associated O 0
with O 0
the O 0
beta O 0
- O 0
adrenoblocking O 0
and O 0
with O 0
the O 0
membrane O 0
- O 0
stabilizing O 0
action O 0
of O 0
the O 0
compound O 0
. O 0

Recurrent O 0
subarachnoid B-Disease 0
hemorrhage I-Disease 0
associated O 0
with O 0
aminocaproic B-Chemical 0
acid I-Chemical 0
therapy O 0
and O 0
acute B-Disease 0
renal I-Disease 0
artery I-Disease 0
thrombosis I-Disease 0
. O 0

Case O 0
report O 0
. O 0

Epsilon B-Chemical 0
aminocaproic I-Chemical 0
acid I-Chemical 0
( O 0
EACA B-Chemical 0
) O 0
has O 0
been O 0
used O 0
to O 0
prevent O 0
rebleeding O 0
in O 0
patients O 0
with O 0
subarachnoid B-Disease 0
hemorrhage I-Disease 0
( O 0
SAH B-Disease 0
) O 0
. O 0

Although O 0
this O 0
agent O 0
does O 0
decrease O 0
the O 0
frequency O 0
of O 0
rebleeding O 0
, O 0
several O 0
reports O 0
have O 0
described O 0
thrombotic B-Disease 0
complications O 0
of O 0
EACA B-Chemical 0
therapy O 0
. O 0

These O 0
complications O 0
have O 0
included O 0
clinical O 0
deterioration O 0
and O 0
intracranial B-Disease 0
vascular I-Disease 0
thrombosis I-Disease 0
in O 0
patients O 0
with O 0
SAH B-Disease 0
, O 0
arteriolar O 0
and O 0
capillary O 0
fibrin O 0
thrombi B-Disease 0
in O 0
patients O 0
with O 0
fibrinolytic O 0
syndromes O 0
treated O 0
with O 0
EACA B-Chemical 0
, O 0
or O 0
other O 0
thromboembolic B-Disease 0
phenomena I-Disease 0
. O 0

Since O 0
intravascular O 0
fibrin O 0
thrombi B-Disease 0
are O 0
often O 0
observed O 0
in O 0
patients O 0
with O 0
fibrinolytic O 0
disorders O 0
, O 0
EACA B-Chemical 0
should O 0
not O 0
be O 0
implicated O 0
in O 0
the O 0
pathogenesis O 0
of O 0
fibrin O 0
thrombi B-Disease 0
in O 0
patients O 0
with O 0
disseminated B-Disease 0
intravascular I-Disease 0
coagulation I-Disease 0
or O 0
other O 0
" O 0
consumption B-Disease 0
coagulopathies I-Disease 0
. O 0
" O 0
This O 0
report O 0
describes O 0
subtotal O 0
infarction B-Disease 0
of O 0
the O 0
kidney O 0
due O 0
to O 0
thrombosis B-Disease 0
of I-Disease 0
a I-Disease 0
normal I-Disease 0
renal I-Disease 0
artery I-Disease 0
. O 0

This O 0
occlusion O 0
occurred O 0
after O 0
EACA B-Chemical 0
therapy O 0
in O 0
a O 0
patient O 0
with O 0
SAH B-Disease 0
and O 0
histopathological O 0
documentation O 0
of O 0
recurrent O 0
SAH B-Disease 0
. O 0

The O 0
corresponding O 0
clinical O 0
event O 0
was O 0
characterized O 0
by O 0
marked O 0
hypertension B-Disease 0
and O 0
abrupt O 0
neurological O 0
deterioration O 0
. O 0

Effect O 0
of O 0
vincristine B-Chemical 0
sulfate I-Chemical 0
on O 0
Pseudomonas B-Disease 0
infections I-Disease 0
in O 0
monkeys O 0
. O 0

In O 0
rhesus O 0
monkeys O 0
, O 0
intravenous O 0
challenge O 0
with O 0
0 O 0
. O 0
6 O 0
x O 0
10 O 0
( O 0
10 O 0
) O 0
to O 0
2 O 0
. O 0
2 O 0
x O 0
10 O 0
( O 0
10 O 0
) O 0
Pseudomonas O 0
aeruginosa O 0
organisms O 0
caused O 0
acute O 0
illness O 0
of O 0
4 O 0
to O 0
5 O 0
days O 0
' O 0
duration O 0
with O 0
spontaneous O 0
recovery O 0
in O 0
13 O 0
of O 0
15 O 0
monkeys O 0
; O 0
blood O 0
cultures O 0
became O 0
negative O 0
3 O 0
to O 0
17 O 0
days O 0
after O 0
challenge O 0
. O 0

Leukocytosis B-Disease 0
was O 0
observed O 0
in O 0
all O 0
monkeys O 0
. O 0

Intravenous O 0
or O 0
intratracheal O 0
inoculation O 0
of O 0
2 O 0
. O 0
0 O 0
to O 0
2 O 0
. O 0
5 O 0
mg O 0
of O 0
vincristine B-Chemical 0
sulfate I-Chemical 0
was O 0
followed O 0
by O 0
leukopenia B-Disease 0
in O 0
4 O 0
to O 0
5 O 0
days O 0
. O 0

Intravenous O 0
inoculation O 0
of O 0
4 O 0
. O 0
2 O 0
x O 0
10 O 0
( O 0
10 O 0
) O 0
to O 0
7 O 0
. O 0
8 O 0
x O 0
10 O 0
( O 0
10 O 0
) O 0
pyocin O 0
type O 0
6 O 0
Pseudomonas O 0
organisms O 0
in O 0
monkeys O 0
given O 0
vincristine B-Chemical 0
sulfate I-Chemical 0
4 O 0
days O 0
previously O 0
resulted O 0
in O 0
fatal O 0
infection B-Disease 0
in O 0
11 O 0
of O 0
14 O 0
monkeys O 0
, O 0
whereas O 0
none O 0
of O 0
four O 0
receiving O 0
Pseudomonas O 0
alone O 0
died O 0
. O 0

These O 0
studies O 0
suggest O 0
that O 0
an O 0
antimetabolite O 0
- O 0
induced O 0
leukopenia B-Disease 0
predisposes O 0
to O 0
severe O 0
Pseudomonas O 0
sepsis B-Disease 0
and O 0
that O 0
such O 0
monkeys O 0
may O 0
serve O 0
as O 0
a O 0
biological O 0
model O 0
for O 0
study O 0
of O 0
comparative O 0
efficacy O 0
of O 0
antimicrobial O 0
agents O 0
. O 0

Modification O 0
by O 0
propranolol B-Chemical 0
of O 0
cardiovascular O 0
effects O 0
of O 0
induced O 0
hypoglycaemia B-Disease 0
. O 0

The O 0
cardiovascular O 0
effects O 0
of O 0
hypoglycaemia B-Disease 0
, O 0
with O 0
and O 0
without O 0
beta O 0
- O 0
blockade O 0
, O 0
were O 0
compared O 0
in O 0
fourteen O 0
healthy O 0
men O 0
. O 0

Eight O 0
received O 0
insulin O 0
alone O 0
, O 0
and O 0
eight O 0
, O 0
including O 0
two O 0
of O 0
the O 0
original O 0
insulin O 0
- O 0
only O 0
group O 0
, O 0
were O 0
given O 0
propranolol B-Chemical 0
and O 0
insulin O 0
. O 0

In O 0
the O 0
insulin O 0
- O 0
group O 0
the O 0
period O 0
of O 0
hypoglycaemia B-Disease 0
was O 0
associated O 0
with O 0
an O 0
increase O 0
in O 0
heart O 0
- O 0
rate O 0
and O 0
a O 0
fall O 0
in O 0
diastolic O 0
blood O 0
- O 0
pressure O 0
. O 0

In O 0
the O 0
propranolol B-Chemical 0
- O 0
insulin O 0
group O 0
there O 0
was O 0
a O 0
significant O 0
fall O 0
in O 0
heart O 0
- O 0
rate O 0
in O 0
most O 0
subjects O 0
and O 0
an O 0
increase O 0
in O 0
diastolic O 0
pressure O 0
. O 0

Typical O 0
S O 0
- O 0
T O 0
/ O 0
T O 0
changes O 0
occurred O 0
in O 0
the O 0
insulin O 0
- O 0
group O 0
but O 0
in O 0
none O 0
of O 0
the O 0
propranolol B-Chemical 0
- O 0
insulin O 0
group O 0
. O 0

Hypertension B-Disease 0
in O 0
diabetics B-Disease 0
prone O 0
to O 0
hypoglycaemia B-Disease 0
attacks O 0
should O 0
not O 0
be O 0
treated O 0
with O 0
beta O 0
- O 0
blockers O 0
because O 0
these O 0
drugs O 0
may O 0
cause O 0
a O 0
sharp O 0
rise O 0
in O 0
blood O 0
- O 0
pressure O 0
in O 0
such O 0
patients O 0
. O 0

Long O 0
- O 0
term O 0
propranolol B-Chemical 0
therapy O 0
in O 0
pregnancy O 0
: O 0
maternal O 0
and O 0
fetal O 0
outcome O 0
. O 0

Propranolol B-Chemical 0
, O 0
a O 0
beta O 0
- O 0
adrenergic O 0
blocking O 0
agent O 0
, O 0
has O 0
found O 0
an O 0
important O 0
position O 0
in O 0
the O 0
practice O 0
of O 0
medicine O 0
. O 0

Its O 0
use O 0
in O 0
pregnancy O 0
, O 0
however O 0
, O 0
is O 0
an O 0
open O 0
question O 0
as O 0
a O 0
number O 0
of O 0
detrimental O 0
side O 0
effects O 0
have O 0
been O 0
reported O 0
in O 0
the O 0
fetus O 0
and O 0
neonate O 0
. O 0

Ten O 0
patients O 0
and O 0
12 O 0
pregnancies O 0
are O 0
reported O 0
where O 0
chronic O 0
propranolol B-Chemical 0
has O 0
been O 0
administered O 0
. O 0

Five O 0
patients O 0
with O 0
serial O 0
pregnancies O 0
with O 0
and O 0
without O 0
propranolol B-Chemical 0
therapy O 0
are O 0
also O 0
examined O 0
. O 0

Maternal O 0
, O 0
fetal O 0
, O 0
and O 0
neonatal O 0
complications O 0
are O 0
examined O 0
. O 0

An O 0
attempt O 0
is O 0
made O 0
to O 0
differentiate O 0
drug O 0
- O 0
related O 0
complications O 0
from O 0
maternal O 0
disease O 0
- O 0
- O 0
related O 0
complications O 0
. O 0

We O 0
conclude O 0
that O 0
previously O 0
reported O 0
hypoglycemia B-Disease 0
, O 0
hyperbilirubinemia B-Disease 0
, O 0
polycythemia B-Disease 0
, O 0
neonatal B-Disease 0
apnea I-Disease 0
, O 0
and O 0
bradycardia B-Disease 0
are O 0
not O 0
invariable O 0
and O 0
cannot O 0
be O 0
statistically O 0
correlated O 0
with O 0
chronic O 0
propranolol B-Chemical 0
therapy O 0
. O 0

Growth B-Disease 0
retardation I-Disease 0
, O 0
however O 0
, O 0
appears O 0
to O 0
be O 0
significant O 0
in O 0
both O 0
of O 0
our O 0
series O 0
. O 0

Central O 0
excitatory O 0
actions O 0
of O 0
flurazepam B-Chemical 0
. O 0

Toxic O 0
actions O 0
of O 0
flurazepam B-Chemical 0
( O 0
FZP B-Chemical 0
) O 0
were O 0
studied O 0
in O 0
cats O 0
, O 0
mice O 0
and O 0
rats O 0
. O 0

High O 0
doses O 0
caused O 0
an O 0
apparent O 0
central O 0
excitation O 0
, O 0
most O 0
clearly O 0
seen O 0
as O 0
clonic O 0
convulsions B-Disease 0
, O 0
superimposed O 0
on O 0
general O 0
depression B-Disease 0
. O 0

Following O 0
a O 0
lethal O 0
dose O 0
, O 0
death O 0
was O 0
always O 0
associated O 0
with O 0
convulsions B-Disease 0
. O 0

Comparing O 0
the O 0
relative O 0
sensitivity O 0
to O 0
central O 0
depression B-Disease 0
and O 0
excitation O 0
revealed O 0
that O 0
rats O 0
were O 0
least O 0
likely O 0
to O 0
have O 0
convulsions B-Disease 0
at O 0
doses O 0
that O 0
did O 0
not O 0
first O 0
cause O 0
loss B-Disease 0
of I-Disease 0
consciousness I-Disease 0
, O 0
while O 0
cats O 0
most O 0
clearly O 0
showed O 0
marked O 0
central O 0
excitatory O 0
actions O 0
. O 0

Signs O 0
of O 0
FZP B-Chemical 0
toxocity B-Disease 0
in O 0
cats O 0
included O 0
excessive O 0
salivation B-Disease 0
, O 0
extreme O 0
apprehensive O 0
behavior O 0
, O 0
retching O 0
, O 0
muscle B-Disease 0
tremors I-Disease 0
and O 0
convulsions B-Disease 0
. O 0

An O 0
interaction O 0
between O 0
FZP B-Chemical 0
and O 0
pentylenetetrazol B-Chemical 0
( O 0
PTZ B-Chemical 0
) O 0
was O 0
shown O 0
by O 0
pretreating O 0
mice O 0
with O 0
FZP B-Chemical 0
before O 0
PTZ B-Chemical 0
challenge O 0
. O 0

As O 0
a O 0
function O 0
of O 0
dose O 0
, O 0
FZP B-Chemical 0
first O 0
protected O 0
against O 0
convulsions B-Disease 0
and O 0
death O 0
. O 0

At O 0
higher O 0
doses O 0
, O 0
however O 0
, O 0
convulsions B-Disease 0
again O 0
emerged O 0
. O 0

These O 0
doses O 0
of O 0
FZP B-Chemical 0
were O 0
lower O 0
than O 0
those O 0
that O 0
would O 0
alone O 0
cause O 0
convulsions B-Disease 0
. O 0

These O 0
results O 0
may O 0
be O 0
relevant O 0
to O 0
the O 0
use O 0
of O 0
FZP B-Chemical 0
in O 0
clinical O 0
situations O 0
in O 0
which O 0
there O 0
is O 0
increased O 0
neural O 0
excitability O 0
, O 0
such O 0
as O 0
epilepsy B-Disease 0
or O 0
sedative O 0
- O 0
hypnotic O 0
drug O 0
withdrawal O 0
. O 0

Use O 0
of O 0
propranolol B-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
idiopathic B-Disease 0
orthostatic I-Disease 0
hypotension I-Disease 0
. O 0

Five O 0
patients O 0
with O 0
idiopathic B-Disease 0
orthostatic I-Disease 0
hypotension I-Disease 0
who O 0
had O 0
physiologic O 0
and O 0
biochemical O 0
evidence O 0
of O 0
severe O 0
autonomic O 0
dysfunction O 0
were O 0
included O 0
in O 0
the O 0
study O 0
. O 0

They O 0
all O 0
exhibited O 0
markedly O 0
reduced O 0
plasma O 0
catecholamines B-Chemical 0
and O 0
plasma O 0
renin O 0
activity O 0
in O 0
both O 0
recumbent O 0
and O 0
upright O 0
positions O 0
and O 0
had O 0
marked O 0
hypersensitivity B-Disease 0
to O 0
the O 0
pressor O 0
effects O 0
of O 0
infused O 0
norepinephrine B-Chemical 0
. O 0

Treatment O 0
with O 0
propanolol B-Chemical 0
administered O 0
intravenously O 0
( O 0
1 O 0
- O 0
5 O 0
mg O 0
) O 0
produced O 0
increases O 0
in O 0
supine O 0
and O 0
upright O 0
blood O 0
pressure O 0
in O 0
4 O 0
of O 0
the O 0
5 O 0
individuals O 0
with O 0
rises O 0
ranging O 0
from O 0
11 O 0
/ O 0
6 O 0
to O 0
22 O 0
/ O 0
11 O 0
mmHg O 0
. O 0

Chronic O 0
oral O 0
administration O 0
of O 0
propranolol B-Chemical 0
( O 0
40 O 0
- O 0
160 O 0
mg O 0
/ O 0
day O 0
) O 0
also O 0
elevated O 0
the O 0
blood O 0
pressures O 0
of O 0
these O 0
individuals O 0
with O 0
increases O 0
in O 0
the O 0
order O 0
of O 0
20 O 0
- O 0
35 O 0
/ O 0
15 O 0
- O 0
25 O 0
mmg O 0
being O 0
observed O 0
. O 0

In O 0
1 O 0
patient O 0
, O 0
marked O 0
hypertension B-Disease 0
was O 0
induced O 0
by O 0
propranolol B-Chemical 0
and O 0
the O 0
drug O 0
had O 0
to O 0
be O 0
withdrawn O 0
. O 0

It O 0
otherwise O 0
was O 0
well O 0
tolerated O 0
and O 0
no O 0
important O 0
side O 0
effects O 0
were O 0
observed O 0
. O 0

Treatment O 0
has O 0
been O 0
continued O 0
in O 0
3 O 0
individuals O 0
for O 0
6 O 0
- O 0
13 O 0
months O 0
with O 0
persistence O 0
of O 0
the O 0
pressor O 0
effect O 0
, O 0
although O 0
there O 0
appears O 0
to O 0
have O 0
been O 0
some O 0
decrease O 0
in O 0
the O 0
degree O 0
of O 0
response O 0
with O 0
time O 0
. O 0

Hemodynamic O 0
measurements O 0
in O 0
1 O 0
of O 0
the O 0
patients O 0
demonstrated O 0
an O 0
increase O 0
in O 0
total O 0
peripheral O 0
resistance O 0
and O 0
essentially O 0
no O 0
change O 0
in O 0
cardiac O 0
output O 0
following O 0
propranolol B-Chemical 0
therapy O 0
. O 0

The O 0
studies O 0
suggest O 0
that O 0
propranolol B-Chemical 0
is O 0
a O 0
useful O 0
drug O 0
in O 0
selected O 0
patients O 0
with O 0
severe O 0
idiopathic B-Disease 0
orthostatic I-Disease 0
hypotension I-Disease 0
. O 0

Total O 0
intravenous O 0
anesthesia O 0
with O 0
etomidate B-Chemical 0
. O 0

III O 0
. O 0

Some O 0
observations O 0
in O 0
adults O 0
. O 0

An O 0
investigation O 0
was O 0
undertaken O 0
to O 0
determine O 0
the O 0
dosage O 0
of O 0
etomidate B-Chemical 0
required O 0
to O 0
maintain O 0
sleep O 0
in O 0
adults O 0
undergoing O 0
surgery O 0
under O 0
regional O 0
local O 0
anesthesia O 0
. O 0

Premedication O 0
of O 0
diazepam B-Chemical 0
10 O 0
mg O 0
and O 0
atropine B-Chemical 0
0 O 0
. O 0
5 O 0
mg O 0
was O 0
given O 0
, O 0
and O 0
sleep O 0
was O 0
induced O 0
and O 0
maintained O 0
by O 0
intermittent O 0
intravenous O 0
injections O 0
of O 0
etomidate B-Chemical 0
0 O 0
. O 0
1 O 0
/ O 0
mg O 0
/ O 0
kg O 0
, O 0
given O 0
whenever O 0
the O 0
patient O 0
would O 0
open O 0
his O 0
eyes O 0
on O 0
request O 0
. O 0

A O 0
mean O 0
overall O 0
dose O 0
of O 0
etomidate B-Chemical 0
17 O 0
. O 0
4 O 0
microgram O 0
/ O 0
kg O 0
/ O 0
min O 0
. O 0
was O 0
required O 0
to O 0
maintain O 0
sleep O 0
, O 0
but O 0
great O 0
individual O 0
variation O 0
occurred O 0
, O 0
with O 0
older O 0
patients O 0
requiring O 0
less O 0
drug O 0
. O 0

The O 0
investigation O 0
was O 0
discontinued O 0
after O 0
18 O 0
patients O 0
because O 0
of O 0
the O 0
frequency O 0
and O 0
intensity O 0
of O 0
side O 0
- O 0
effects O 0
, O 0
particularly O 0
pain B-Disease 0
and O 0
myoclonia B-Disease 0
, O 0
which O 0
caused O 0
the O 0
technique O 0
to O 0
be O 0
abandoned O 0
in O 0
two O 0
cases O 0
. O 0

It O 0
is O 0
considered O 0
unlikely O 0
that O 0
etomidate B-Chemical 0
will O 0
prove O 0
to O 0
be O 0
the O 0
hypnotic O 0
of O 0
choice O 0
for O 0
a O 0
totally O 0
intravenous O 0
anesthetic O 0
technique O 0
in O 0
adults O 0
because O 0
of O 0
the O 0
high O 0
incidence O 0
of O 0
myoclonia B-Disease 0
after O 0
prolonged O 0
administration O 0
. O 0

In O 0
several O 0
patients O 0
uncontrollable O 0
muscle O 0
movements O 0
persisted O 0
for O 0
many O 0
minutes O 0
after O 0
complete O 0
recovery O 0
of O 0
consciousness O 0
. O 0

Evidence O 0
for O 0
cardiac O 0
beta O 0
2 O 0
- O 0
adrenoceptors O 0
in O 0
man O 0
. O 0

We O 0
compared O 0
the O 0
effects O 0
of O 0
single O 0
doses O 0
of O 0
50 O 0
mg O 0
atenolol B-Chemical 0
( O 0
cardioselective O 0
) O 0
, O 0
40 O 0
mg O 0
propranolol B-Chemical 0
( O 0
nonselective O 0
) O 0
, O 0
and O 0
placebo O 0
on O 0
both O 0
exercise O 0
- O 0
and O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
tachycardia B-Disease 0
in O 0
two O 0
experiments O 0
involving O 0
nine O 0
normal O 0
subjects O 0
. O 0

Maximal O 0
exercise O 0
heart O 0
rate O 0
was O 0
reduced O 0
from O 0
187 O 0
+ O 0
/ O 0
- O 0
4 O 0
( O 0
SEM O 0
) O 0
after O 0
placebo O 0
to O 0
146 O 0
+ O 0
/ O 0
- O 0
7 O 0
bpm O 0
after O 0
atenolol B-Chemical 0
and O 0
138 O 0
+ O 0
/ O 0
- O 0
6 O 0
bpm O 0
after O 0
propranolol B-Chemical 0
, O 0
but O 0
there O 0
were O 0
no O 0
differences O 0
between O 0
the O 0
drugs O 0
. O 0

The O 0
effects O 0
on O 0
isoproterenol B-Chemical 0
tachycardia B-Disease 0
were O 0
determined O 0
before O 0
and O 0
after O 0
atropine B-Chemical 0
( O 0
0 O 0
. O 0
04 O 0
mg O 0
/ O 0
kg O 0
IV O 0
) O 0
. O 0

Isoproterenol B-Chemical 0
sensitivity O 0
was O 0
determined O 0
as O 0
the O 0
intravenous O 0
dose O 0
that O 0
increased O 0
heart O 0
rate O 0
by O 0
25 O 0
bpm O 0
( O 0
CD25 O 0
) O 0
and O 0
this O 0
was O 0
increased O 0
from O 0
1 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
3 O 0
micrograms O 0
after O 0
placebo O 0
to O 0
38 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
8 O 0
. O 0
3 O 0
micrograms O 0
after O 0
propranolol B-Chemical 0
and O 0
8 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
7 O 0
micrograms O 0
after O 0
atenolol B-Chemical 0
. O 0

The O 0
difference O 0
in O 0
the O 0
effects O 0
of O 0
the O 0
two O 0
was O 0
significant O 0
. O 0

After O 0
atropine B-Chemical 0
the O 0
CD25 O 0
was O 0
unchanged O 0
after O 0
placebo O 0
( O 0
2 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
3 O 0
micrograms O 0
) O 0
and O 0
atenolol B-Chemical 0
( O 0
7 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
3 O 0
micrograms O 0
) O 0
; O 0
it O 0
was O 0
reduced O 0
after O 0
propranolol B-Chemical 0
( O 0
24 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
5 O 0
. O 0
0 O 0
micrograms O 0
) O 0
, O 0
but O 0
remained O 0
different O 0
from O 0
atenolol B-Chemical 0
. O 0

This O 0
change O 0
with O 0
propranolol B-Chemical 0
sensitivity O 0
was O 0
calculated O 0
as O 0
the O 0
apparent O 0
Ka O 0
, O 0
this O 0
was O 0
unchanged O 0
by O 0
atropine B-Chemical 0
( O 0
11 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
1 O 0
and O 0
10 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
5 O 0
ml O 0
/ O 0
ng O 0
) O 0
. O 0

These O 0
data O 0
are O 0
consistent O 0
with O 0
the O 0
hypothesis O 0
that O 0
exercise O 0
- O 0
induced O 0
tachycardia B-Disease 0
results O 0
largely O 0
from O 0
beta O 0
1 O 0
- O 0
receptor O 0
activation O 0
that O 0
is O 0
blocked O 0
by O 0
both O 0
cardioselective O 0
and O 0
nonselective O 0
drugs O 0
, O 0
whereas O 0
isoproterenol B-Chemical 0
activates O 0
both O 0
beta O 0
1 O 0
- O 0
and O 0
beta O 0
2 O 0
- O 0
receptors O 0
so O 0
that O 0
after O 0
cardioselective O 0
blockade O 0
there O 0
remains O 0
a O 0
beta O 0
2 O 0
- O 0
component O 0
that O 0
can O 0
be O 0
blocked O 0
with O 0
a O 0
nonselective O 0
drug O 0
. O 0

While O 0
there O 0
appear O 0
to O 0
be O 0
beta O 0
2 O 0
- O 0
receptors O 0
in O 0
the O 0
human O 0
heart O 0
, O 0
their O 0
physiologic O 0
or O 0
pathologic O 0
roles O 0
remain O 0
to O 0
be O 0
defined O 0
. O 0

Hormones O 0
and O 0
risk O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

This O 0
paper O 0
reports O 0
the O 0
results O 0
of O 0
a O 0
study O 0
of O 0
50 O 0
menopausal O 0
women O 0
receiving O 0
hormonal O 0
replacement O 0
therapy O 0
. O 0

The O 0
majority O 0
( O 0
29 O 0
) O 0
had O 0
surgical O 0
menopause O 0
; O 0
their O 0
mean O 0
age O 0
was O 0
45 O 0
. O 0
7 O 0
years O 0
. O 0

It O 0
was O 0
hypothesized O 0
that O 0
progestins B-Chemical 0
could O 0
equilibrate O 0
the O 0
effects O 0
of O 0
the O 0
estrogenic O 0
stimulation O 0
on O 0
the O 0
mammary O 0
and O 0
endometrial O 0
target O 0
tissues O 0
of O 0
women O 0
on O 0
hormonal O 0
replacement O 0
therapy O 0
. O 0

The O 0
treatment O 0
schedule O 0
consisted O 0
of O 0
conjugated B-Chemical 0
estrogens I-Chemical 0
( O 0
Premarin B-Chemical 0
) O 0
1 O 0
. O 0
25 O 0
mg O 0
/ O 0
day O 0
for O 0
21 O 0
days O 0
and O 0
Medroxyprogesterone B-Chemical 0
acetate I-Chemical 0
10 O 0
mg O 0
/ O 0
day O 0
for O 0
10 O 0
days O 0
in O 0
each O 0
month O 0
. O 0

The O 0
mean O 0
treatment O 0
period O 0
was O 0
18 O 0
months O 0
. O 0

During O 0
the O 0
follow O 0
- O 0
up O 0
period O 0
, O 0
attention O 0
was O 0
paid O 0
to O 0
breast O 0
modifications O 0
as O 0
evidenced O 0
by O 0
symptomatology O 0
, O 0
physical O 0
examination O 0
, O 0
and O 0
plate O 0
thermography O 0
. O 0

Mastodynia B-Disease 0
was O 0
reported O 0
by O 0
21 O 0
patients O 0
, O 0
and O 0
physical O 0
examination O 0
revealed O 0
a O 0
light O 0
increase O 0
in O 0
breast O 0
firmness O 0
in O 0
12 O 0
women O 0
and O 0
a O 0
moderate O 0
increase O 0
in O 0
breast O 0
nodularity O 0
in O 0
2 O 0
women O 0
. O 0

Themography O 0
confirmed O 0
the O 0
existence O 0
of O 0
an O 0
excessive O 0
breast O 0
stimulation O 0
in O 0
1 O 0
women O 0
who O 0
complained O 0
of O 0
moderate O 0
mastodynia B-Disease 0
and O 0
in O 0
5 O 0
of O 0
the O 0
7 O 0
women O 0
who O 0
complained O 0
of O 0
severe O 0
mastodynia B-Disease 0
. O 0

Normalization O 0
was O 0
obtained O 0
by O 0
halving O 0
the O 0
estrogen B-Chemical 0
dose O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
hormonal O 0
replacement O 0
therapy O 0
can O 0
be O 0
safely O 0
prescribed O 0
if O 0
the O 0
following O 0
criteria O 0
are O 0
satisfied O 0
: O 0
1 O 0
) O 0
preliminary O 0
evaluation O 0
of O 0
patients O 0
from O 0
a O 0
clinical O 0
, O 0
metabolic O 0
, O 0
cytologic O 0
, O 0
and O 0
mammographic O 0
perspective O 0
; O 0
2 O 0
) O 0
cyclic O 0
treatment O 0
schedule O 0
, O 0
with O 0
a O 0
progestative O 0
phase O 0
of O 0
10 O 0
days O 0
; O 0
and O 0
3 O 0
) O 0
periodic O 0
complete O 0
follow O 0
- O 0
up O 0
, O 0
with O 0
accurate O 0
thermographic O 0
evaluation O 0
of O 0
the O 0
breast O 0
target O 0
tissues O 0
. O 0

Early O 0
infections B-Disease 0
in O 0
kidney O 0
, O 0
heart O 0
, O 0
and O 0
liver O 0
transplant O 0
recipients O 0
on O 0
cyclosporine B-Chemical 0
. O 0

Eighty O 0
- O 0
one O 0
renal O 0
, O 0
seventeen O 0
heart O 0
, O 0
and O 0
twenty O 0
- O 0
four O 0
liver O 0
transplant O 0
patients O 0
were O 0
followed O 0
for O 0
infection B-Disease 0
. O 0

Seventeen O 0
renal O 0
patients O 0
received O 0
azathioprine B-Chemical 0
( O 0
Aza B-Chemical 0
) O 0
and O 0
prednisone B-Chemical 0
as O 0
part O 0
of O 0
a O 0
randomized O 0
trial O 0
of O 0
immunosuppression O 0
with O 0
21 O 0
cyclosporine B-Chemical 0
- O 0
and O 0
- O 0
prednisone B-Chemical 0
- O 0
treated O 0
renal O 0
transplant O 0
patients O 0
. O 0

All O 0
others O 0
received O 0
cyclosporine B-Chemical 0
and O 0
prednisone B-Chemical 0
. O 0

The O 0
randomized O 0
Aza B-Chemical 0
patients O 0
had O 0
more O 0
overall O 0
infections B-Disease 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
and O 0
more O 0
nonviral O 0
infections B-Disease 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
02 O 0
) O 0
than O 0
the O 0
randomized O 0
cyclosporine B-Chemical 0
patients O 0
. O 0

Heart O 0
and O 0
liver O 0
patients O 0
had O 0
more O 0
infections B-Disease 0
than O 0
cyclosporine B-Chemical 0
renal O 0
patients O 0
but O 0
fewer O 0
infections B-Disease 0
than O 0
the O 0
Aza B-Chemical 0
renal O 0
patients O 0
. O 0

There O 0
were O 0
no O 0
infectious O 0
deaths O 0
in O 0
renal O 0
transplant O 0
patients O 0
on O 0
cyclosporine B-Chemical 0
or O 0
Aza B-Chemical 0
, O 0
but O 0
infection B-Disease 0
played O 0
a O 0
major O 0
role O 0
in O 0
3 O 0
out O 0
of O 0
6 O 0
cardiac O 0
transplant O 0
deaths O 0
and O 0
in O 0
8 O 0
out O 0
of O 0
9 O 0
liver O 0
transplant O 0
deaths O 0
. O 0

Renal O 0
patients O 0
on O 0
cyclosporine B-Chemical 0
had O 0
the O 0
fewest O 0
bacteremias B-Disease 0
. O 0

Analysis O 0
of O 0
site O 0
of O 0
infection B-Disease 0
showed O 0
a O 0
preponderance O 0
of O 0
abdominal B-Disease 0
infections I-Disease 0
in O 0
liver O 0
patients O 0
, O 0
intrathoracic O 0
infections B-Disease 0
in O 0
heart O 0
patients O 0
, O 0
and O 0
urinary B-Disease 0
tract I-Disease 0
infections I-Disease 0
in O 0
renal O 0
patients O 0
. O 0

Pulmonary O 0
infections B-Disease 0
were O 0
less O 0
common O 0
in O 0
cyclosporine B-Chemical 0
- O 0
treated O 0
renal O 0
patients O 0
than O 0
in O 0
Aza B-Chemical 0
- O 0
treated O 0
patients O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Aza B-Chemical 0
patients O 0
had O 0
significantly O 0
more O 0
staphylococcal B-Disease 0
infections I-Disease 0
than O 0
all O 0
other O 0
transplant O 0
groups O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
005 O 0
) O 0
, O 0
and O 0
systemic O 0
fungal B-Disease 0
infections I-Disease 0
occurred O 0
only O 0
in O 0
the O 0
liver O 0
transplant O 0
group O 0
. O 0

Cytomegalovirus O 0
( O 0
CMV O 0
) O 0
shedding O 0
or O 0
serological O 0
rises O 0
in O 0
antibody O 0
titer O 0
, O 0
or O 0
both O 0
occurred O 0
in O 0
78 O 0
% O 0
of O 0
cyclosporine B-Chemical 0
patients O 0
and O 0
76 O 0
% O 0
of O 0
Aza B-Chemical 0
patients O 0
. O 0

Of O 0
the O 0
cyclosporine B-Chemical 0
patients O 0
, O 0
15 O 0
% O 0
had O 0
symptoms O 0
related O 0
to O 0
CMV B-Disease 0
infection I-Disease 0
. O 0

Serological O 0
evidence O 0
for O 0
Epstein B-Disease 0
Barr I-Disease 0
Virus I-Disease 0
infection I-Disease 0
was O 0
found O 0
in O 0
20 O 0
% O 0
of O 0
65 O 0
cyclosporine B-Chemical 0
patients O 0
studied O 0
. O 0

Three O 0
had O 0
associated O 0
symptoms O 0
, O 0
and O 0
one O 0
developed O 0
a O 0
lymphoma B-Disease 0
. O 0

Structure O 0
- O 0
activity O 0
and O 0
dose O 0
- O 0
effect O 0
relationships O 0
of O 0
the O 0
antagonism O 0
of O 0
picrotoxin B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
by O 0
cholecystokinin B-Chemical 0
, O 0
fragments O 0
and O 0
analogues O 0
of O 0
cholecystokinin B-Chemical 0
in O 0
mice O 0
. O 0

Intraperitoneal O 0
administration O 0
of O 0
cholecystokinin B-Chemical 0
octapeptide I-Chemical 0
sulphate O 0
ester O 0
( O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
- O 0
SE O 0
) O 0
and O 0
nonsulphated O 0
cholecystokinin B-Chemical 0
octapeptide I-Chemical 0
( O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
- O 0
NS O 0
) O 0
enhanced O 0
the O 0
latency O 0
of O 0
seizures B-Disease 0
induced O 0
by O 0
picrotoxin B-Chemical 0
in O 0
mice O 0
. O 0

Experiments O 0
with O 0
N O 0
- O 0
and O 0
C O 0
- O 0
terminal O 0
fragments O 0
revealed O 0
that O 0
the O 0
C O 0
- O 0
terminal O 0
tetrapeptide O 0
( O 0
CCK O 0
- O 0
5 O 0
- O 0
8 O 0
) O 0
was O 0
the O 0
active O 0
centre O 0
of O 0
the O 0
CCK O 0
octapeptide O 0
molecule O 0
. O 0

The O 0
analogues O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
- O 0
SE O 0
and O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
- O 0
NS O 0
( O 0
dose O 0
range O 0
0 O 0
. O 0
2 O 0
- O 0
6 O 0
. O 0
4 O 0
mumol O 0
/ O 0
kg O 0
) O 0
and O 0
caerulein B-Chemical 0
dose O 0
range O 0
0 O 0
. O 0
1 O 0
- O 0
0 O 0
. O 0
8 O 0
mumol O 0
/ O 0
kg O 0
) O 0
showed O 0
bell O 0
- O 0
shaped O 0
dose O 0
- O 0
effect O 0
curves O 0
, O 0
with O 0
the O 0
greatest O 0
maximum O 0
inhibition O 0
for O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
- O 0
NS O 0
. O 0

The O 0
peptide O 0
CCK O 0
- O 0
5 O 0
- O 0
8 O 0
had O 0
weak O 0
anticonvulsant O 0
activity O 0
in O 0
comparison O 0
to O 0
the O 0
octapeptides O 0
, O 0
3 O 0
. O 0
2 O 0
mumol O 0
/ O 0
kg O 0
and O 0
larger O 0
doses O 0
of O 0
the O 0
reference O 0
drug O 0
, O 0
diazepam B-Chemical 0
, O 0
totally O 0
prevented O 0
picrotoxin B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
and O 0
mortality O 0
. O 0

The O 0
maximum O 0
effect O 0
of O 0
the O 0
peptides O 0
tested O 0
was O 0
less O 0
than O 0
that O 0
of O 0
diazepam B-Chemical 0
. O 0

Experiments O 0
with O 0
analogues O 0
and O 0
derivatives O 0
of O 0
CCK O 0
- O 0
5 O 0
- O 0
8 O 0
demonstrated O 0
that O 0
the O 0
effectiveness O 0
of O 0
the O 0
beta O 0
- O 0
alanyl O 0
derivatives O 0
of O 0
CCK O 0
- O 0
5 O 0
- O 0
8 O 0
were O 0
enhanced O 0
and O 0
that O 0
they O 0
were O 0
equipotent O 0
with O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
- O 0
SE O 0
. O 0

Of O 0
the O 0
CCK O 0
- O 0
2 O 0
- O 0
8 O 0
analogues O 0
, O 0
Ser O 0
( O 0
SO3H O 0
) O 0
7 O 0
- O 0
Ac O 0
- O 0
CCK O 0
- O 0
2 O 0
- O 0
8 O 0
- O 0
SE O 0
and O 0
Thr O 0
( O 0
SO3H O 0
) O 0
7 O 0
- O 0
Ac O 0
- O 0
CCK O 0
- O 0
2 O 0
- O 0
8 O 0
- O 0
SE O 0
and O 0
Hyp O 0
( O 0
SO3H O 0
) O 0
- O 0
Ac O 0
- O 0
CCK O 0
- O 0
2 O 0
- O 0
8 O 0
- O 0
SE O 0
were O 0
slightly O 0
more O 0
active O 0
than O 0
CCK B-Chemical 0
- I-Chemical 0
8 I-Chemical 0
- O 0
SE O 0
. O 0

Vasopressin B-Chemical 0
as O 0
a O 0
possible O 0
contributor O 0
to O 0
hypertension B-Disease 0
. O 0

The O 0
role O 0
of O 0
vasopressin B-Chemical 0
as O 0
a O 0
pressor O 0
agent O 0
to O 0
the O 0
hypertensive B-Disease 0
process O 0
was O 0
examined O 0
. O 0

Vasopressin B-Chemical 0
plays O 0
a O 0
major O 0
role O 0
in O 0
the O 0
pathogenesis O 0
of O 0
DOCA B-Chemical 0
- O 0
salt O 0
hypertension B-Disease 0
, O 0
since O 0
the O 0
elevation O 0
of O 0
blood O 0
pressure O 0
was O 0
not O 0
substantial O 0
in O 0
the O 0
rats O 0
with O 0
lithium B-Chemical 0
- O 0
treated O 0
diabetes B-Disease 0
insipidus I-Disease 0
after O 0
DOCA B-Chemical 0
- O 0
salt O 0
treatment O 0
. O 0

Administration O 0
of O 0
DDAVP B-Chemical 0
which O 0
has O 0
antidiuretic O 0
action O 0
but O 0
minimal O 0
vasopressor O 0
effect O 0
failed O 0
to O 0
increase O 0
blood O 0
pressure O 0
to O 0
the O 0
levels O 0
observed O 0
after O 0
administration O 0
of O 0
AVP O 0
. O 0

Furthermore O 0
, O 0
the O 0
pressor O 0
action O 0
of O 0
vasopressin B-Chemical 0
appears O 0
to O 0
be O 0
important O 0
in O 0
the O 0
development O 0
of O 0
this O 0
model O 0
of O 0
hypertension B-Disease 0
, O 0
since O 0
the O 0
enhanced O 0
pressor O 0
responsiveness O 0
to O 0
the O 0
hormone O 0
was O 0
observed O 0
in O 0
the O 0
initial O 0
stage O 0
of O 0
hypertension B-Disease 0
. O 0

Increased O 0
secretion O 0
of O 0
vasopressin B-Chemical 0
from O 0
neurohypophysis O 0
also O 0
promotes O 0
the O 0
function O 0
of O 0
the O 0
hormone O 0
as O 0
a O 0
pathogenetic O 0
factor O 0
in O 0
hypertension B-Disease 0
. O 0

An O 0
unproportional O 0
release O 0
of O 0
vasopressin B-Chemical 0
compared O 0
to O 0
plasma O 0
osmolality O 0
may O 0
be O 0
induced O 0
by O 0
the O 0
absence O 0
of O 0
an O 0
adjusting O 0
control O 0
of O 0
angiotensin B-Chemical 0
II O 0
forming O 0
and O 0
receptor O 0
binding O 0
capacity O 0
for O 0
sodium B-Chemical 0
balance O 0
in O 0
the O 0
brain O 0
. O 0

However O 0
, O 0
the O 0
role O 0
of O 0
vasopressin B-Chemical 0
remains O 0
to O 0
be O 0
determined O 0
in O 0
human O 0
essential O 0
hypertension B-Disease 0
. O 0

Toxic B-Disease 0
hepatitis I-Disease 0
induced O 0
by O 0
disulfiram B-Chemical 0
in O 0
a O 0
non O 0
- O 0
alcoholic O 0
. O 0

A O 0
reversible O 0
toxic B-Disease 0
liver I-Disease 0
damage I-Disease 0
was O 0
observed O 0
in O 0
a O 0
non O 0
- O 0
alcoholic O 0
woman O 0
treated O 0
with O 0
disulfiram B-Chemical 0
. O 0

The O 0
causative O 0
relationship O 0
was O 0
proven O 0
by O 0
challenge O 0
. O 0

Atrial B-Disease 0
thrombosis I-Disease 0
involving O 0
the O 0
heart O 0
of O 0
F O 0
- O 0
344 O 0
rats O 0
ingesting O 0
quinacrine B-Chemical 0
hydrochloride I-Chemical 0
. O 0

Quinacrine B-Chemical 0
hydrochloride I-Chemical 0
is O 0
toxic O 0
for O 0
the O 0
heart O 0
of O 0
F O 0
- O 0
344 O 0
rats O 0
. O 0

Rats O 0
treated O 0
with O 0
500 O 0
ppm O 0
quinacrine B-Chemical 0
hydrochloride I-Chemical 0
in O 0
the O 0
diet O 0
all O 0
developed O 0
a O 0
high O 0
incidence O 0
of O 0
left O 0
atrial B-Disease 0
thrombosis I-Disease 0
. O 0

The O 0
lesion O 0
was O 0
associated O 0
with O 0
cardiac B-Disease 0
hypertrophy I-Disease 0
and O 0
dilatation O 0
and O 0
focal O 0
myocardial B-Disease 0
degeneration I-Disease 0
. O 0

Rats O 0
died O 0
from O 0
cardiac B-Disease 0
hypertrophy I-Disease 0
with O 0
severe O 0
acute O 0
and O 0
chronic O 0
congestion O 0
of O 0
the O 0
lungs O 0
, O 0
liver O 0
, O 0
and O 0
other O 0
organs O 0
. O 0

Seventy O 0
percent O 0
of O 0
rats O 0
given O 0
250 O 0
ppm O 0
quinacrine B-Chemical 0
hydrochloride I-Chemical 0
and O 0
1 O 0
, O 0
000 O 0
ppm O 0
sodium B-Chemical 0
nitrite I-Chemical 0
simultaneously O 0
in O 0
the O 0
diet O 0
had O 0
thrombosis B-Disease 0
of O 0
the O 0
atria O 0
of O 0
the O 0
heart O 0
, O 0
while O 0
untreated O 0
control O 0
rats O 0
in O 0
this O 0
laboratory O 0
did O 0
not O 0
have O 0
atrial B-Disease 0
thrombosis I-Disease 0
. O 0

Sodium B-Chemical 0
nitrite I-Chemical 0
in O 0
combination O 0
with O 0
quinacrine B-Chemical 0
hydrochloride I-Chemical 0
appeared O 0
to O 0
have O 0
no O 0
additional O 0
effect O 0
. O 0

Alternating B-Disease 0
sinus I-Disease 0
rhythm I-Disease 0
and O 0
intermittent O 0
sinoatrial B-Disease 0
block I-Disease 0
induced O 0
by O 0
propranolol B-Chemical 0
. O 0

Alternating B-Disease 0
sinus I-Disease 0
rhythm I-Disease 0
and O 0
intermittent O 0
sinoatrial B-Disease 0
( I-Disease 0
S I-Disease 0
- I-Disease 0
A I-Disease 0
) I-Disease 0
block I-Disease 0
was O 0
observed O 0
in O 0
a O 0
57 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
, O 0
under O 0
treatment O 0
for O 0
angina B-Disease 0
with O 0
80 O 0
mg O 0
propranolol B-Chemical 0
daily O 0
. O 0

The O 0
electrocardiogram O 0
showed O 0
alternation O 0
of O 0
long O 0
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short O 0
P O 0
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P O 0
intervals O 0
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. O 0

These O 0
pauses O 0
were O 0
always O 0
preceded O 0
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usually O 0
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0 O 0
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92 O 0
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95 O 0
s O 0
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basic O 0
sinus O 0
cycle O 0
. O 0

Following O 0
these O 0
basic O 0
sinus O 0
cycles O 0
, O 0
alternating B-Disease 0
rhythm I-Disease 0
started O 0
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the O 0
longer O 0
P O 0
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interval O 0
. O 0

The O 0
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P O 0
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P O 0
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1 O 0
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04 O 0
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s O 0
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P O 0
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0 O 0
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80 O 0
- O 0
0 O 0
. O 0
84 O 0
s O 0
, O 0
respectively O 0
. O 0

The O 0
duration O 0
of O 0
the O 0
pauses O 0
were O 0
equal O 0
or O 0
almost O 0
equal O 0
to O 0
one O 0
short O 0
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one O 0
long O 0
P O 0
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P O 0
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cycle O 0
. O 0

In O 0
one O 0
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period O 0
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intermittent O 0
2 O 0
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1 O 0
S B-Disease 0
- I-Disease 0
A I-Disease 0
block I-Disease 0
was O 0
observed O 0
. O 0

This O 0
short O 0
period O 0
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sinus O 0
rhythm O 0
was O 0
interrupted O 0
by O 0
sudden O 0
prolongation O 0
of O 0
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P O 0
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P O 0
interval O 0
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alternative O 0
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. O 0

There O 0
were O 0
small O 0
changes O 0
in O 0
the O 0
shape O 0
of O 0
the O 0
P O 0
waves O 0
and O 0
P O 0
- O 0
R O 0
intervals O 0
. O 0

S O 0
- O 0
A O 0
conduction O 0
through O 0
two O 0
pathways O 0
, O 0
the O 0
first O 0
with O 0
2 O 0
/ O 0
1 O 0
block O 0
the O 0
second O 0
having O 0
0 O 0
. O 0
12 O 0
- O 0
0 O 0
. O 0
14 O 0
s O 0
longer O 0
conduction O 0
time O 0
and O 0
with O 0
occasional O 0
2 O 0
/ O 0
1 O 0
block O 0
was O 0
proposed O 0
for O 0
the O 0
explanation O 0
of O 0
the O 0
alternating O 0
P O 0
- O 0
P O 0
interval O 0
and O 0
other O 0
electrocardiographic O 0
features O 0
seen O 0
. O 0

Atropine B-Chemical 0
1 O 0
mg O 0
given O 0
intravenously O 0
resulted O 0
in O 0
shortening O 0
of O 0
all O 0
P O 0
- O 0
P O 0
intervals O 0
without O 0
changing O 0
the O 0
rhythm O 0
. O 0

The O 0
abnormal O 0
rhythm O 0
disappeared O 0
with O 0
the O 0
withdrawal O 0
of O 0
propranolol B-Chemical 0
and O 0
when O 0
the O 0
drug O 0
was O 0
restarted O 0
a O 0
2 O 0
/ O 0
1 O 0
S B-Disease 0
- I-Disease 0
A I-Disease 0
block I-Disease 0
was O 0
seen O 0
. O 0

This O 0
was O 0
accepted O 0
as O 0
evidence O 0
for O 0
propranolol B-Chemical 0
being O 0
the O 0
cause O 0
of O 0
this O 0
conduction B-Disease 0
disorder I-Disease 0
. O 0

Antitumor O 0
effect O 0
, O 0
cardiotoxicity B-Disease 0
, O 0
and O 0
nephrotoxicity B-Disease 0
of O 0
doxorubicin B-Chemical 0
in O 0
the O 0
IgM O 0
solid O 0
immunocytoma B-Disease 0
- O 0
bearing O 0
LOU O 0
/ O 0
M O 0
/ O 0
WSL O 0
rat O 0
. O 0

Antitumor O 0
activity O 0
, O 0
cardiotoxicity B-Disease 0
, O 0
and O 0
nephrotoxicity B-Disease 0
induced O 0
by O 0
doxorubicin B-Chemical 0
were O 0
studied O 0
in O 0
LOU O 0
/ O 0
M O 0
/ O 0
WSL O 0
inbred O 0
rats O 0
each O 0
bearing O 0
a O 0
transplantable O 0
solid O 0
IgM O 0
immunocytoma B-Disease 0
. O 0

Animals O 0
with O 0
a O 0
tumor B-Disease 0
( O 0
diameter O 0
, O 0
15 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
3 O 0
mm O 0
) O 0
were O 0
treated O 0
with O 0
iv O 0
injections O 0
of O 0
doxorubicin B-Chemical 0
on O 0
5 O 0
consecutive O 0
days O 0
, O 0
followed O 0
by O 0
1 O 0
weekly O 0
injection O 0
for O 0
7 O 0
weeks O 0
( O 0
dose O 0
range O 0
, O 0
0 O 0
. O 0
015 O 0
- O 0
4 O 0
. O 0
0 O 0
mg O 0
/ O 0
kg O 0
body O 0
wt O 0
) O 0
. O 0

Tumor B-Disease 0
regression O 0
was O 0
observed O 0
with O 0
0 O 0
. O 0
5 O 0
mg O 0
doxorubicin B-Chemical 0
/ O 0
kg O 0
. O 0

Complete O 0
disappearance O 0
of O 0
the O 0
tumor B-Disease 0
was O 0
induced O 0
with O 0
1 O 0
. O 0
0 O 0
mg O 0
doxorubicin B-Chemical 0
/ O 0
kg O 0
. O 0

Histologic O 0
evidence O 0
of O 0
cardiotoxicity B-Disease 0
scored O 0
as O 0
grade O 0
III O 0
was O 0
only O 0
observed O 0
at O 0
a O 0
dose O 0
of O 0
1 O 0
. O 0
0 O 0
mg O 0
doxorubicin B-Chemical 0
/ O 0
kg O 0
. O 0

Light O 0
microscopic O 0
evidence O 0
of O 0
renal B-Disease 0
damage I-Disease 0
was O 0
seen O 0
above O 0
a O 0
dose O 0
of O 0
0 O 0
. O 0
5 O 0
mg O 0
doxorubicin B-Chemical 0
/ O 0
kg O 0
, O 0
which O 0
resulted O 0
in O 0
albuminuria B-Disease 0
and O 0
very O 0
low O 0
serum O 0
albumin O 0
levels O 0
. O 0

In O 0
the O 0
group O 0
that O 0
received O 0
1 O 0
. O 0
0 O 0
mg O 0
doxorubicin B-Chemical 0
/ O 0
kg O 0
, O 0
the O 0
serum O 0
albumin O 0
level O 0
decreased O 0
from O 0
33 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
1 O 0
to O 0
1 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
5 O 0
g O 0
/ O 0
liter O 0
. O 0

Ascites B-Disease 0
and O 0
hydrothorax B-Disease 0
were O 0
observed O 0
simultaneously O 0
. O 0

The O 0
same O 0
experiments O 0
were O 0
performed O 0
with O 0
non O 0
- O 0
tumor B-Disease 0
- O 0
bearing O 0
rats O 0
, O 0
in O 0
which O 0
no O 0
major O 0
differences O 0
were O 0
observed O 0
. O 0

In O 0
conclusion O 0
, O 0
antitumor O 0
activity O 0
, O 0
cardiotoxicity B-Disease 0
, O 0
and O 0
nephrotoxicity B-Disease 0
were O 0
studied O 0
simultaneously O 0
in O 0
the O 0
same O 0
LOU O 0
/ O 0
M O 0
/ O 0
WSL O 0
rat O 0
. O 0

Albuminuria B-Disease 0
due O 0
to O 0
renal B-Disease 0
damage I-Disease 0
led O 0
to O 0
extremely O 0
low O 0
serum O 0
albumin O 0
levels O 0
, O 0
so O 0
ascites B-Disease 0
and O 0
hydrothorax B-Disease 0
were O 0
not O 0
necessarily O 0
a O 0
consequence O 0
of O 0
the O 0
observed O 0
cardiomyopathy B-Disease 0
. O 0

Intraoperative O 0
bradycardia B-Disease 0
and O 0
hypotension B-Disease 0
associated O 0
with O 0
timolol B-Chemical 0
and O 0
pilocarpine B-Chemical 0
eye O 0
drops O 0
. O 0

A O 0
69 O 0
- O 0
yr O 0
- O 0
old O 0
man O 0
, O 0
who O 0
was O 0
concurrently O 0
being O 0
treated O 0
with O 0
pilocarpine B-Chemical 0
nitrate I-Chemical 0
and O 0
timolol B-Chemical 0
maleate I-Chemical 0
eye O 0
drops O 0
, O 0
developed O 0
a O 0
bradycardia B-Disease 0
and O 0
became O 0
hypotensive B-Disease 0
during O 0
halothane B-Chemical 0
anaesthesia O 0
. O 0

Both O 0
timolol B-Chemical 0
and O 0
pilocarpine B-Chemical 0
were O 0
subsequently O 0
identified O 0
in O 0
a O 0
24 O 0
- O 0
h O 0
collection O 0
of O 0
urine O 0
. O 0

Timolol B-Chemical 0
( O 0
but O 0
not O 0
pilocarpine B-Chemical 0
) O 0
was O 0
detected O 0
in O 0
a O 0
sample O 0
of O 0
plasma O 0
removed O 0
during O 0
surgery O 0
; O 0
the O 0
plasma O 0
concentration O 0
of O 0
timolol B-Chemical 0
( O 0
2 O 0
. O 0
6 O 0
ng O 0
ml O 0
- O 0
1 O 0
) O 0
was O 0
consistent O 0
with O 0
partial O 0
beta O 0
- O 0
adrenoceptor O 0
blockade O 0
. O 0

It O 0
is O 0
postulated O 0
that O 0
this O 0
action O 0
may O 0
have O 0
been O 0
enhanced O 0
during O 0
halothane B-Chemical 0
anaesthesia O 0
with O 0
resultant O 0
bradycardia B-Disease 0
and O 0
hypotension B-Disease 0
. O 0

Pilocarpine B-Chemical 0
may O 0
have O 0
had O 0
a O 0
contributory O 0
effect O 0
. O 0

Succinylcholine B-Chemical 0
apnoea B-Disease 0
: O 0
attempted O 0
reversal O 0
with O 0
anticholinesterases O 0
. O 0

Anticholinesterases O 0
were O 0
administered O 0
in O 0
an O 0
attempt O 0
to O 0
antagonize O 0
prolonged O 0
neuromuscular B-Disease 0
blockade I-Disease 0
following O 0
the O 0
administration O 0
of O 0
succinylcholine B-Chemical 0
in O 0
a O 0
patient O 0
later O 0
found O 0
to O 0
be O 0
homozygous O 0
for O 0
atypical O 0
plasma O 0
cholinesterase O 0
. O 0

Edrophonium B-Chemical 0
10 O 0
mg O 0
, O 0
given O 0
74 O 0
min O 0
after O 0
succinylcholine B-Chemical 0
, O 0
when O 0
train O 0
- O 0
of O 0
- O 0
four O 0
stimulation O 0
was O 0
characteristic O 0
of O 0
phase O 0
II O 0
block O 0
, O 0
produced O 0
partial O 0
antagonism O 0
which O 0
was O 0
not O 0
sustained O 0
. O 0

Repeated O 0
doses O 0
of O 0
edrophonium B-Chemical 0
to O 0
70 O 0
mg O 0
and O 0
neostigmine B-Chemical 0
to O 0
2 O 0
. O 0
5 O 0
mg O 0
did O 0
not O 0
antagonize O 0
or O 0
augment O 0
the O 0
block O 0
. O 0

Spontaneous O 0
respiration O 0
recommenced O 0
200 O 0
min O 0
after O 0
succinylcholine B-Chemical 0
administration O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
anticholinesterases O 0
are O 0
only O 0
partially O 0
effective O 0
in O 0
restoring O 0
neuromuscular O 0
function O 0
in O 0
succinylcholine B-Chemical 0
apnoea B-Disease 0
despite O 0
muscle O 0
twitch O 0
activity O 0
typical O 0
of O 0
phase O 0
II O 0
block O 0
. O 0

Effect O 0
of O 0
doxorubicin B-Chemical 0
on O 0
[ B-Chemical 0
omega I-Chemical 0
- I-Chemical 0
I I-Chemical 0
- I-Chemical 0
131 I-Chemical 0
] I-Chemical 0
heptadecanoic I-Chemical 0
acid I-Chemical 0
myocardial O 0
scintigraphy O 0
and O 0
echocardiography O 0
in O 0
dogs O 0
. O 0

The O 0
effects O 0
of O 0
serial O 0
treatment O 0
with O 0
doxorubicin B-Chemical 0
on O 0
dynamic O 0
myocardial O 0
scintigraphy O 0
with O 0
[ B-Chemical 0
omega I-Chemical 0
- I-Chemical 0
I I-Chemical 0
- I-Chemical 0
131 I-Chemical 0
] I-Chemical 0
heptadecanoic I-Chemical 0
acid I-Chemical 0
( O 0
I B-Chemical 0
- I-Chemical 0
131 I-Chemical 0
HA I-Chemical 0
) O 0
, O 0
and O 0
on O 0
global O 0
left O 0
- O 0
ventricular O 0
function O 0
determined O 0
echocardiographically O 0
, O 0
were O 0
studied O 0
in O 0
a O 0
group O 0
of O 0
nine O 0
mongrel O 0
dogs O 0
. O 0

Total O 0
extractable O 0
myocardial O 0
lipid O 0
was O 0
compared O 0
postmortem O 0
between O 0
a O 0
group O 0
of O 0
control O 0
dogs O 0
and O 0
doxorubicin B-Chemical 0
- O 0
treated O 0
dogs O 0
. O 0

A O 0
significant O 0
and O 0
then O 0
progressive O 0
fall O 0
in O 0
global O 0
LV O 0
function O 0
was O 0
observed O 0
at O 0
a O 0
cumulative O 0
doxorubicin B-Chemical 0
dose O 0
of O 0
4 O 0
mg O 0
/ O 0
kg O 0
. O 0

A O 0
significant O 0
increase O 0
in O 0
the O 0
myocardial O 0
t1 O 0
/ O 0
2 O 0
of O 0
the O 0
I B-Chemical 0
- I-Chemical 0
131 I-Chemical 0
HA I-Chemical 0
was O 0
observed O 0
only O 0
at O 0
a O 0
higher O 0
cumulative O 0
dose O 0
, O 0
10 O 0
mg O 0
/ O 0
kg O 0
. O 0

No O 0
significant O 0
alteration O 0
in O 0
total O 0
extractable O 0
myocardial O 0
lipids O 0
was O 0
observed O 0
between O 0
control O 0
dogs O 0
and O 0
those O 0
treated O 0
with O 0
doxorubicin B-Chemical 0
. O 0

Our O 0
findings O 0
suggest O 0
that O 0
the O 0
changes O 0
leading O 0
to O 0
an O 0
alteration O 0
of O 0
myocardial O 0
dynamic O 0
imaging O 0
with O 0
I B-Chemical 0
- I-Chemical 0
131 I-Chemical 0
HA I-Chemical 0
are O 0
not O 0
the O 0
initiating O 0
factor O 0
in O 0
doxorubicin B-Chemical 0
cardiotoxicity B-Disease 0
. O 0

Hemodynamics O 0
and O 0
myocardial O 0
metabolism O 0
under O 0
deliberate O 0
hypotension B-Disease 0
. O 0

An O 0
experimental O 0
study O 0
in O 0
dogs O 0
. O 0

Coronary O 0
blood O 0
flow O 0
, O 0
cardiac O 0
work O 0
and O 0
metabolism O 0
were O 0
studied O 0
in O 0
dogs O 0
under O 0
sodium B-Chemical 0
nitroprusside I-Chemical 0
( O 0
SNP B-Chemical 0
) O 0
and O 0
trimetaphan B-Chemical 0
( O 0
TMP B-Chemical 0
) O 0
deliberate O 0
hypotension B-Disease 0
( O 0
20 O 0
% O 0
and O 0
40 O 0
% O 0
mean O 0
pressure O 0
decrease O 0
from O 0
baseline O 0
) O 0
. O 0

Regarding O 0
the O 0
effects O 0
of O 0
drug O 0
- O 0
induced O 0
hypotension B-Disease 0
on O 0
coronary O 0
blood O 0
flow O 0
, O 0
aortic O 0
and O 0
coronary O 0
sinus O 0
metabolic O 0
data O 0
( O 0
pH O 0
, O 0
pO2 O 0
, O 0
pCO2 O 0
) O 0
we O 0
could O 0
confirm O 0
that O 0
nitroprusside B-Chemical 0
hypotension B-Disease 0
could O 0
be O 0
safely O 0
used O 0
to O 0
30 O 0
% O 0
mean O 0
blood O 0
pressure O 0
decrease O 0
from O 0
control O 0
, O 0
trimetaphan B-Chemical 0
hypotension B-Disease 0
to O 0
20 O 0
% O 0
mean O 0
blood O 0
pressure O 0
decrease O 0
. O 0

Cardiac O 0
work O 0
was O 0
significantly O 0
reduced O 0
during O 0
SNP B-Chemical 0
hypotension B-Disease 0
. O 0

Myocardial O 0
O2 B-Chemical 0
consumption O 0
and O 0
O2 B-Chemical 0
availability O 0
were O 0
directly O 0
dependent O 0
on O 0
the O 0
coronary O 0
perfusion O 0
. O 0

Careful O 0
invasive O 0
monitoring O 0
of O 0
the O 0
blood O 0
pressure O 0
, O 0
blood O 0
gases O 0
and O 0
of O 0
the O 0
ECG O 0
ST O 0
- O 0
T O 0
segment O 0
is O 0
mandatory O 0
. O 0

Evidence O 0
for O 0
a O 0
selective O 0
brain O 0
noradrenergic O 0
involvement O 0
in O 0
the O 0
locomotor O 0
stimulant O 0
effects O 0
of O 0
amphetamine B-Chemical 0
in O 0
the O 0
rat O 0
. O 0

Male O 0
rats O 0
received O 0
the O 0
noradrenaline B-Chemical 0
neurotoxin O 0
DSP4 B-Chemical 0
( O 0
50 O 0
mg O 0
/ O 0
kg O 0
) O 0
7 O 0
days O 0
prior O 0
to O 0
injection O 0
of O 0
D B-Chemical 0
- I-Chemical 0
amphetamine I-Chemical 0
( O 0
10 O 0
or O 0
40 O 0
mumol O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

The O 0
hyperactivity B-Disease 0
induced O 0
by O 0
D B-Chemical 0
- I-Chemical 0
amphetamine I-Chemical 0
( O 0
10 O 0
mumol O 0
/ O 0
kg O 0
) O 0
was O 0
significantly O 0
reduced O 0
by O 0
DSP4 B-Chemical 0
pretreatment O 0
. O 0

However O 0
, O 0
the O 0
increased O 0
rearings O 0
and O 0
the O 0
amphetamine B-Chemical 0
- O 0
induced O 0
stereotypies B-Disease 0
were O 0
not O 0
blocked O 0
by O 0
pretreatment O 0
with O 0
DSP4 B-Chemical 0
. O 0

The O 0
reduction O 0
of O 0
amphetamine B-Chemical 0
hyperactivity B-Disease 0
induced O 0
by O 0
DSP4 B-Chemical 0
was O 0
blocked O 0
by O 0
pretreatment O 0
with O 0
the O 0
noradrenaline B-Chemical 0
- O 0
uptake O 0
blocking O 0
agent O 0
, O 0
desipramine B-Chemical 0
, O 0
which O 0
prevents O 0
the O 0
neurotoxic B-Disease 0
action O 0
of O 0
DSP4 B-Chemical 0
. O 0

The O 0
present O 0
results O 0
suggest O 0
a O 0
selective O 0
involvement O 0
of O 0
central O 0
noradrenergic O 0
neurones O 0
in O 0
the O 0
locomotor O 0
stimulant O 0
effect O 0
of O 0
amphetamine B-Chemical 0
in O 0
the O 0
rat O 0
. O 0

Accelerated B-Disease 0
junctional I-Disease 0
rhythms I-Disease 0
during O 0
oral O 0
verapamil B-Chemical 0
therapy O 0
. O 0

This O 0
study O 0
examined O 0
the O 0
frequency O 0
of O 0
atrioventricular O 0
( O 0
AV O 0
) O 0
dissociation O 0
and O 0
accelerated B-Disease 0
junctional I-Disease 0
rhythms I-Disease 0
in O 0
59 O 0
patients O 0
receiving O 0
oral O 0
verapamil B-Chemical 0
. O 0

Accelerated B-Disease 0
junctional I-Disease 0
rhythms I-Disease 0
and O 0
AV O 0
dissociation O 0
were O 0
frequent O 0
in O 0
patients O 0
with O 0
supraventricular B-Disease 0
tachyarrhythmias I-Disease 0
, O 0
particularly O 0
AV O 0
nodal O 0
reentry O 0
. O 0

Verapamil B-Chemical 0
administration O 0
to O 0
these O 0
patients O 0
led O 0
to O 0
an O 0
asymptomatic O 0
increase O 0
in O 0
activity O 0
of O 0
these O 0
junctional O 0
pacemakers O 0
. O 0

In O 0
patients O 0
with O 0
various O 0
chest B-Disease 0
pain I-Disease 0
syndromes O 0
, O 0
verapamil B-Chemical 0
neither O 0
increased O 0
the O 0
frequency O 0
of O 0
junctional O 0
rhythms O 0
nor O 0
suppressed O 0
their O 0
role O 0
as O 0
escape O 0
rhythms O 0
under O 0
physiologically O 0
appropriate O 0
circumstances O 0
. O 0

Interstrain O 0
variation O 0
in O 0
acute O 0
toxic O 0
response O 0
to O 0
caffeine B-Chemical 0
among O 0
inbred O 0
mice O 0
. O 0

Acute O 0
toxic O 0
dosage O 0
- O 0
dependent O 0
behavioral O 0
effects O 0
of O 0
caffeine B-Chemical 0
were O 0
compared O 0
in O 0
adult O 0
males O 0
from O 0
seven O 0
inbred O 0
mouse O 0
strains O 0
( O 0
A O 0
/ O 0
J O 0
, O 0
BALB O 0
/ O 0
cJ O 0
, O 0
CBA O 0
/ O 0
J O 0
, O 0
C3H O 0
/ O 0
HeJ O 0
, O 0
C57BL O 0
/ O 0
6J O 0
, O 0
DBA O 0
/ O 0
2J O 0
, O 0
SWR O 0
/ O 0
J O 0
) O 0
. O 0

C57BL O 0
/ O 0
6J O 0
, O 0
chosen O 0
as O 0
a O 0
" O 0
prototypic O 0
" O 0
mouse O 0
strain O 0
, O 0
was O 0
used O 0
to O 0
determine O 0
behavioral O 0
responses O 0
to O 0
a O 0
broad O 0
range O 0
( O 0
5 O 0
- O 0
500 O 0
mg O 0
/ O 0
kg O 0
) O 0
of O 0
caffeine B-Chemical 0
doses O 0
. O 0

Five O 0
phenotypic O 0
characteristics O 0
- O 0
- O 0
locomotor O 0
activity O 0
, O 0
righting O 0
ability O 0
, O 0
clonic B-Disease 0
seizure I-Disease 0
induction O 0
, O 0
stress O 0
- O 0
induced O 0
lethality O 0
, O 0
death O 0
without O 0
external O 0
stress O 0
- O 0
- O 0
were O 0
scored O 0
at O 0
various O 0
caffeine B-Chemical 0
doses O 0
in O 0
drug O 0
- O 0
naive O 0
animals O 0
under O 0
empirically O 0
optimized O 0
, O 0
rigidly O 0
constant O 0
experimental O 0
conditions O 0
. O 0

Mice O 0
( O 0
n O 0
= O 0
12 O 0
for O 0
each O 0
point O 0
) O 0
received O 0
single O 0
IP O 0
injections O 0
of O 0
a O 0
fixed O 0
volume O 0
/ O 0
g O 0
body O 0
weight O 0
of O 0
physiological O 0
saline O 0
carrier O 0
with O 0
or O 0
without O 0
caffeine B-Chemical 0
in O 0
doses O 0
ranging O 0
from O 0
125 O 0
- O 0
500 O 0
mg O 0
/ O 0
kg O 0
. O 0

Loss O 0
of O 0
righting O 0
ability O 0
was O 0
scored O 0
at O 0
1 O 0
, O 0
3 O 0
, O 0
5 O 0
min O 0
post O 0
dosing O 0
and O 0
at O 0
5 O 0
min O 0
intervals O 0
thereafter O 0
for O 0
20 O 0
min O 0
. O 0

In O 0
the O 0
same O 0
animals O 0
the O 0
occurrence O 0
of O 0
clonic B-Disease 0
seizures I-Disease 0
was O 0
scored O 0
as O 0
to O 0
time O 0
of O 0
onset O 0
and O 0
severity O 0
for O 0
20 O 0
min O 0
after O 0
drug O 0
administration O 0
. O 0

When O 0
these O 0
proceeded O 0
to O 0
tonic B-Disease 0
seizures I-Disease 0
, O 0
death O 0
occurred O 0
in O 0
less O 0
than O 0
20 O 0
min O 0
. O 0

Animals O 0
surviving O 0
for O 0
20 O 0
min O 0
were O 0
immediately O 0
stressed O 0
by O 0
a O 0
swim O 0
test O 0
in O 0
25 O 0
degrees O 0
C O 0
water O 0
, O 0
and O 0
death O 0
- O 0
producing O 0
tonic B-Disease 0
seizures I-Disease 0
were O 0
scored O 0
for O 0
2 O 0
min O 0
. O 0

In O 0
other O 0
animals O 0
locomotor O 0
activity O 0
was O 0
measured O 0
15 O 0
or O 0
60 O 0
min O 0
after O 0
caffeine B-Chemical 0
administration O 0
. O 0

By O 0
any O 0
single O 0
behavioral O 0
criterion O 0
or O 0
a O 0
combination O 0
of O 0
these O 0
criteria O 0
, O 0
marked O 0
differences O 0
in O 0
response O 0
to O 0
toxic O 0
caffeine B-Chemical 0
doses O 0
were O 0
observed O 0
between O 0
strains O 0
. O 0

These O 0
results O 0
indicate O 0
that O 0
behavioral O 0
toxicity B-Disease 0
testing O 0
of O 0
alkylxanthines B-Chemical 0
in O 0
a O 0
single O 0
mouse O 0
strain O 0
may O 0
be O 0
misleading O 0
and O 0
suggest O 0
that O 0
toxic O 0
responses O 0
of O 0
the O 0
central O 0
nervous O 0
system O 0
to O 0
this O 0
class O 0
of O 0
compounds O 0
are O 0
genetically O 0
influenced O 0
in O 0
mammals O 0
. O 0

Treatment O 0
of O 0
ovarian B-Disease 0
cancer I-Disease 0
with O 0
a O 0
combination O 0
of O 0
cis B-Chemical 0
- I-Chemical 0
platinum I-Chemical 0
, O 0
adriamycin B-Chemical 0
, O 0
cyclophosphamide B-Chemical 0
and O 0
hexamethylmelamine B-Chemical 0
. O 0

During O 0
the O 0
last O 0
2 O 0
1 O 0
/ O 0
2 O 0
years O 0
, O 0
38 O 0
patients O 0
with O 0
ovarian B-Disease 0
cancer I-Disease 0
were O 0
treated O 0
with O 0
a O 0
combination O 0
of O 0
cisplatinum B-Chemical 0
( O 0
CPDD B-Chemical 0
) O 0
, O 0
50 O 0
mg O 0
/ O 0
m2 O 0
, O 0
adriamycin B-Chemical 0
, O 0
30 O 0
mg O 0
/ O 0
m2 O 0
, O 0
cyclophosphamide B-Chemical 0
, O 0
300 O 0
mg O 0
/ O 0
m2 O 0
, O 0
on O 0
day O 0
1 O 0
; O 0
and O 0
hexamethylmelamine B-Chemical 0
( O 0
HMM B-Chemical 0
) O 0
, O 0
6 O 0
mg O 0
/ O 0
kg O 0
daily O 0
, O 0
for O 0
14 O 0
days O 0
. O 0

Each O 0
course O 0
was O 0
repeated O 0
monthly O 0
. O 0

2 O 0
patients O 0
had O 0
stage O 0
II O 0
, O 0
14 O 0
stage O 0
III O 0
and O 0
22 O 0
stage O 0
IV O 0
disease O 0
. O 0

14 O 0
of O 0
the O 0
38 O 0
patients O 0
were O 0
previously O 0
treated O 0
with O 0
chemotherapy O 0
, O 0
1 O 0
with O 0
radiation O 0
, O 0
6 O 0
with O 0
both O 0
chemotherapy O 0
and O 0
radiation O 0
, O 0
and O 0
17 O 0
did O 0
not O 0
have O 0
any O 0
treatment O 0
before O 0
CPDD B-Chemical 0
combination O 0
. O 0

31 O 0
of O 0
the O 0
38 O 0
cases O 0
( O 0
81 O 0
. O 0
5 O 0
% O 0
) O 0
demonstrated O 0
objective O 0
responses O 0
lasting O 0
for O 0
2 O 0
months O 0
or O 0
more O 0
. O 0

These O 0
responses O 0
were O 0
partial O 0
in O 0
19 O 0
and O 0
complete O 0
in O 0
12 O 0
cases O 0
. O 0

Hematologic B-Disease 0
toxicity I-Disease 0
was O 0
moderate O 0
and O 0
with O 0
reversible O 0
anemia B-Disease 0
developing O 0
in O 0
71 O 0
% O 0
of O 0
patients O 0
. O 0

Gastrointestinal O 0
side O 0
effects O 0
from O 0
CPDD B-Chemical 0
were O 0
universal O 0
. O 0

HMM B-Chemical 0
gastrointestinal B-Disease 0
toxicity I-Disease 0
necessitated O 0
discontinuation O 0
of O 0
the O 0
drug O 0
in O 0
5 O 0
patients O 0
. O 0

Severe O 0
nephrotoxicity B-Disease 0
was O 0
observed O 0
in O 0
2 O 0
patients O 0
but O 0
was O 0
reversible O 0
. O 0

There O 0
were O 0
no O 0
drug O 0
- O 0
related O 0
deaths O 0
. O 0

Nontraumatic O 0
dissecting B-Disease 0
aneurysm I-Disease 0
of O 0
the O 0
basilar O 0
artery O 0
. O 0

A O 0
case O 0
of O 0
nontraumatic O 0
dissecting B-Disease 0
aneurysm I-Disease 0
of O 0
the O 0
basilar O 0
artery O 0
in O 0
association O 0
with O 0
hypertension B-Disease 0
, O 0
smoke O 0
, O 0
and O 0
oral B-Chemical 0
contraceptives I-Chemical 0
is O 0
reported O 0
in O 0
a O 0
young O 0
female O 0
patient O 0
with O 0
a O 0
locked B-Disease 0
- I-Disease 0
in I-Disease 0
syndrome I-Disease 0
. O 0

A O 0
method O 0
for O 0
the O 0
measurement O 0
of O 0
tremor B-Disease 0
, O 0
and O 0
a O 0
comparison O 0
of O 0
the O 0
effects O 0
of O 0
tocolytic O 0
beta O 0
- O 0
mimetics O 0
. O 0

A O 0
method O 0
permitting O 0
measurement O 0
of O 0
finger O 0
tremor B-Disease 0
as O 0
a O 0
displacement O 0
- O 0
time O 0
curve O 0
is O 0
described O 0
, O 0
using O 0
a O 0
test O 0
system O 0
with O 0
simple O 0
amplitude O 0
calibration O 0
. O 0

The O 0
coordinates O 0
of O 0
the O 0
inversion O 0
points O 0
of O 0
the O 0
displacement O 0
- O 0
time O 0
curves O 0
were O 0
transferred O 0
through O 0
graphical O 0
input O 0
equipment O 0
to O 0
punched O 0
tape O 0
. O 0

By O 0
means O 0
of O 0
a O 0
computer O 0
program O 0
, O 0
periods O 0
and O 0
amplitudes O 0
of O 0
tremor B-Disease 0
oscillations O 0
were O 0
calculated O 0
and O 0
classified O 0
. O 0

The O 0
event O 0
frequency O 0
for O 0
each O 0
class O 0
of O 0
periods O 0
and O 0
amplitudes O 0
was O 0
determined O 0
. O 0

The O 0
actions O 0
of O 0
fenoterol B-Chemical 0
- I-Chemical 0
hydrobromide I-Chemical 0
, O 0
ritodrin B-Chemical 0
- I-Chemical 0
HCl I-Chemical 0
and O 0
placebo O 0
given O 0
to O 0
10 O 0
healthy O 0
subjects O 0
by O 0
intravenous O 0
infusion O 0
in O 0
a O 0
double O 0
- O 0
blind O 0
crossover O 0
study O 0
were O 0
tested O 0
by O 0
this O 0
method O 0
. O 0

At O 0
therapeutic O 0
doses O 0
both O 0
substances O 0
raised O 0
the O 0
mean O 0
tremor B-Disease 0
amplitude O 0
to O 0
about O 0
three O 0
times O 0
the O 0
control O 0
level O 0
. O 0

At O 0
the O 0
same O 0
time O 0
, O 0
the O 0
mean O 0
period O 0
within O 0
each O 0
class O 0
of O 0
amplitudes O 0
shortened O 0
by O 0
10 O 0
- O 0
- O 0
20 O 0
ms O 0
, O 0
whereas O 0
the O 0
mean O 0
periods O 0
calculated O 0
from O 0
all O 0
oscillations O 0
together O 0
did O 0
not O 0
change O 0
significantly O 0
. O 0

After O 0
the O 0
end O 0
of O 0
fenoterol B-Chemical 0
- I-Chemical 0
hydrobromide I-Chemical 0
infusion O 0
, O 0
tremor B-Disease 0
amplitudes O 0
decreased O 0
significantly O 0
faster O 0
than O 0
those O 0
following O 0
ritodrin B-Chemical 0
- I-Chemical 0
HCl I-Chemical 0
infusion O 0
. O 0

Propylthiouracil B-Chemical 0
- O 0
induced O 0
hepatic B-Disease 0
damage I-Disease 0
. O 0

Two O 0
cases O 0
of O 0
propylthiouracil B-Chemical 0
- O 0
induced O 0
liver B-Disease 0
damage I-Disease 0
have O 0
been O 0
observed O 0
. O 0

The O 0
first O 0
case O 0
is O 0
of O 0
an O 0
acute O 0
type O 0
of O 0
damage O 0
, O 0
proven O 0
by O 0
rechallenge O 0
; O 0
the O 0
second O 0
presents O 0
a O 0
clinical O 0
and O 0
histologic O 0
picture O 0
resembling O 0
chronic B-Disease 0
active I-Disease 0
hepatitis I-Disease 0
, O 0
with O 0
spontaneous O 0
remission O 0
. O 0

Studies O 0
on O 0
the O 0
bradycardia B-Disease 0
induced O 0
by O 0
bepridil B-Chemical 0
. O 0

Bepridil B-Chemical 0
, O 0
a O 0
novel O 0
active O 0
compound O 0
for O 0
prophylactic O 0
treatment O 0
of O 0
anginal B-Disease 0
attacks I-Disease 0
, O 0
induced O 0
persistent O 0
bradycardia B-Disease 0
and O 0
a O 0
non O 0
- O 0
specific O 0
anti O 0
- O 0
tachycardial B-Disease 0
effect O 0
, O 0
the O 0
mechanisms O 0
of O 0
which O 0
were O 0
investigated O 0
in O 0
vitro O 0
and O 0
in O 0
vivo O 0
. O 0

In O 0
vitro O 0
perfusion O 0
of O 0
bepridil B-Chemical 0
in O 0
the O 0
life O 0
- O 0
support O 0
medium O 0
for O 0
isolated O 0
sino O 0
- O 0
atrial O 0
tissue O 0
from O 0
rabbit O 0
heart O 0
, O 0
caused O 0
a O 0
reduction O 0
in O 0
action O 0
potential O 0
( O 0
AP O 0
) O 0
spike O 0
frequency O 0
( O 0
recorded O 0
by O 0
KCl B-Chemical 0
microelectrodes O 0
) O 0
starting O 0
at O 0
doses O 0
of O 0
5 O 0
X O 0
10 O 0
( O 0
- O 0
6 O 0
) O 0
M O 0
. O 0

This O 0
effect O 0
was O 0
dose O 0
- O 0
dependent O 0
up O 0
to O 0
concentrations O 0
of O 0
5 O 0
X O 0
10 O 0
( O 0
- O 0
5 O 0
) O 0
M O 0
, O 0
whereupon O 0
blockade O 0
of O 0
sinus O 0
activity O 0
set O 0
in O 0
. O 0

Bepridil B-Chemical 0
at O 0
a O 0
dose O 0
of O 0
5 O 0
X O 0
10 O 0
( O 0
- O 0
6 O 0
) O 0
M O 0
, O 0
induced O 0
a O 0
concomitant O 0
reduction O 0
in O 0
AP O 0
amplitude O 0
( O 0
falling O 0
from O 0
71 O 0
+ O 0
/ O 0
- O 0
8 O 0
mV O 0
to O 0
47 O 0
+ O 0
/ O 0
- O 0
6 O 0
mV O 0
) O 0
, O 0
maximum O 0
systolic O 0
depolarization O 0
velocity O 0
( O 0
phase O 0
0 O 0
) O 0
which O 0
fell O 0
from O 0
1 O 0
. O 0
85 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
35 O 0
V O 0
/ O 0
s O 0
to O 0
0 O 0
. O 0
84 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
28 O 0
V O 0
/ O 0
s O 0
, O 0
together O 0
with O 0
maximum O 0
diastolic O 0
depolarization O 0
velocity O 0
( O 0
phase O 0
4 O 0
) O 0
which O 0
fell O 0
from O 0
38 O 0
+ O 0
/ O 0
- O 0
3 O 0
mV O 0
/ O 0
s O 0
to O 0
24 O 0
+ O 0
/ O 0
- O 0
5 O 0
mV O 0
/ O 0
s O 0
. O 0

In O 0
vivo O 0
injection O 0
of O 0
bepridil B-Chemical 0
at O 0
a O 0
dose O 0
of O 0
5 O 0
mg O 0
/ O 0
kg O 0
( O 0
i O 0
. O 0
v O 0
. O 0
) O 0
into O 0
6 O 0
anaesthetized O 0
dogs O 0
which O 0
had O 0
undergone O 0
ablation O 0
of O 0
all O 0
the O 0
extrinsic O 0
cardiac O 0
afferent O 0
nerve O 0
supply O 0
, O 0
together O 0
with O 0
a O 0
bilateral O 0
medullo O 0
- O 0
adrenalectomy O 0
, O 0
caused O 0
a O 0
marked O 0
reduction O 0
in O 0
heart O 0
rate O 0
which O 0
fell O 0
from O 0
98 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
2 O 0
beats O 0
/ O 0
min O 0
to O 0
76 O 0
+ O 0
/ O 0
- O 0
5 O 0
. O 0
3 O 0
beats O 0
/ O 0
min O 0
sustained O 0
for O 0
more O 0
than O 0
45 O 0
min O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
bepridil B-Chemical 0
reduces O 0
heart O 0
rate O 0
by O 0
acting O 0
directly O 0
on O 0
the O 0
sinus O 0
node O 0
. O 0

This O 0
effect O 0
, O 0
which O 0
results O 0
in O 0
a O 0
flattening O 0
of O 0
the O 0
phase O 0
0 O 0
and O 0
phase O 0
4 O 0
slope O 0
, O 0
together O 0
with O 0
a O 0
longer O 0
AP O 0
duration O 0
, O 0
may O 0
be O 0
due O 0
to O 0
an O 0
increase O 0
in O 0
the O 0
time O 0
constants O 0
of O 0
slow O 0
inward O 0
ionic O 0
currents O 0
( O 0
already O 0
demonstrated O 0
elsewhere O 0
) O 0
, O 0
but O 0
also O 0
to O 0
an O 0
increased O 0
time O 0
constant O 0
for O 0
deactivation O 0
of O 0
the O 0
outward O 0
potassium B-Chemical 0
current O 0
( O 0
Ip O 0
) O 0
. O 0

Hepatitis B-Disease 0
and O 0
renal B-Disease 0
tubular I-Disease 0
acidosis I-Disease 0
after O 0
anesthesia O 0
with O 0
methoxyflurane B-Chemical 0
. O 0

A O 0
69 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
operated O 0
for O 0
acute B-Disease 0
cholecystitis I-Disease 0
under O 0
methoxyflurane B-Chemical 0
anesthesia O 0
developed O 0
postoperatively O 0
a O 0
hepatic B-Disease 0
insufficiency I-Disease 0
syndrome I-Disease 0
and O 0
renal B-Disease 0
tubular I-Disease 0
acidosis I-Disease 0
. O 0

Massive O 0
bleeding B-Disease 0
appeared O 0
during O 0
surgery O 0
which O 0
lasted O 0
for O 0
six O 0
hours O 0
. O 0

Postoperative O 0
evolution O 0
under O 0
supportive O 0
therapy O 0
was O 0
favourable O 0
. O 0

Complete O 0
recovery O 0
was O 0
confirmed O 0
by O 0
repeated O 0
controls O 0
performed O 0
over O 0
a O 0
period O 0
of O 0
one O 0
year O 0
after O 0
surgery O 0
. O 0

Pituitary O 0
response O 0
to O 0
luteinizing O 0
hormone O 0
- O 0
releasing O 0
hormone O 0
during O 0
haloperidol B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
. O 0

The O 0
effects O 0
of O 0
a O 0
6 O 0
- O 0
hour O 0
infusion O 0
with O 0
haloperidol B-Chemical 0
on O 0
serum O 0
prolactin O 0
and O 0
luteinizing O 0
hormone O 0
( O 0
LH O 0
) O 0
levels O 0
was O 0
studied O 0
in O 0
a O 0
group O 0
of O 0
male O 0
subjects O 0
. O 0

Five O 0
hours O 0
after O 0
starting O 0
the O 0
infusions O 0
, O 0
a O 0
study O 0
of O 0
the O 0
pituitary O 0
responses O 0
to O 0
LH O 0
- O 0
releasing O 0
hormone O 0
( O 0
LH O 0
- O 0
RH O 0
) O 0
was O 0
carried O 0
out O 0
. O 0

Control O 0
patients O 0
received O 0
infusions O 0
of O 0
0 O 0
. O 0
9 O 0
% O 0
NaCl B-Chemical 0
solution O 0
. O 0

During O 0
the O 0
course O 0
of O 0
haloperidol B-Chemical 0
infusions O 0
, O 0
significant O 0
hyperprolactinemia B-Disease 0
was O 0
found O 0
, O 0
together O 0
with O 0
an O 0
abolished O 0
pituitary O 0
response O 0
to O 0
LH O 0
- O 0
RH O 0
, O 0
as O 0
compared O 0
with O 0
responses O 0
of O 0
control O 0
subjects O 0
. O 0

Antirifampicin O 0
antibodies O 0
in O 0
acute O 0
rifampicin B-Chemical 0
- O 0
associated O 0
renal B-Disease 0
failure I-Disease 0
. O 0

5 O 0
patients O 0
with O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
( O 0
3 O 0
with O 0
thrombopenia B-Disease 0
and O 0
hemolysis B-Disease 0
) O 0
induced O 0
by O 0
the O 0
reintroduction O 0
of O 0
rifampicin B-Chemical 0
are O 0
described O 0
. O 0

No O 0
correlation O 0
was O 0
found O 0
between O 0
the O 0
severity O 0
of O 0
clinical O 0
manifestations O 0
and O 0
the O 0
total O 0
dose O 0
taken O 0
by O 0
the O 0
patients O 0
. O 0

In O 0
all O 0
but O 0
1 O 0
patient O 0
, O 0
antirifampicin O 0
antibodies O 0
were O 0
detected O 0
. O 0

Antibodies O 0
suggested O 0
to O 0
be O 0
of O 0
the O 0
IgM O 0
class O 0
were O 0
detected O 0
in O 0
all O 0
3 O 0
patients O 0
with O 0
hematological B-Disease 0
disorders I-Disease 0
. O 0

The O 0
pattern O 0
of O 0
non O 0
- O 0
specific O 0
acute B-Disease 0
tubular I-Disease 0
necrosis I-Disease 0
found O 0
in O 0
the O 0
2 O 0
biopsied O 0
patients O 0
, O 0
indistinguishable O 0
from O 0
that O 0
of O 0
ischemic O 0
origin O 0
, O 0
raised O 0
the O 0
possibility O 0
of O 0
a O 0
vascular O 0
- O 0
mediated O 0
damage O 0
. O 0

In O 0
3 O 0
patients O 0
, O 0
the O 0
possibility O 0
of O 0
a O 0
triggering O 0
immunoallergic O 0
mechanism O 0
is O 0
discussed O 0
. O 0

Cardiovascular O 0
effects O 0
of O 0
hypotension B-Disease 0
induced O 0
by O 0
adenosine B-Chemical 0
triphosphate I-Chemical 0
and O 0
sodium B-Chemical 0
nitroprusside I-Chemical 0
on O 0
dogs O 0
with O 0
denervated O 0
hearts O 0
. O 0

Adenosine B-Chemical 0
triphosphate I-Chemical 0
( O 0
ATP B-Chemical 0
) O 0
and O 0
sodium B-Chemical 0
nitroprusside I-Chemical 0
( O 0
SNP B-Chemical 0
) O 0
are O 0
administered O 0
to O 0
patients O 0
to O 0
induce O 0
and O 0
control O 0
hypotension B-Disease 0
during O 0
anesthesia O 0
. O 0

SNP B-Chemical 0
is O 0
authorized O 0
for O 0
clinical O 0
use O 0
in O 0
USA O 0
and O 0
UK O 0
, O 0
and O 0
ATP B-Chemical 0
is O 0
clinically O 0
used O 0
in O 0
other O 0
countries O 0
such O 0
as O 0
Japan O 0
. O 0

We O 0
investigated O 0
how O 0
these O 0
two O 0
drugs O 0
act O 0
on O 0
the O 0
cardiovascular O 0
systems O 0
of O 0
20 O 0
dogs O 0
whose O 0
hearts O 0
had O 0
been O 0
denervated O 0
by O 0
a O 0
procedure O 0
we O 0
had O 0
devised O 0
. O 0

ATP B-Chemical 0
( O 0
10 O 0
dogs O 0
) O 0
or O 0
SNP B-Chemical 0
( O 0
10 O 0
dogs O 0
) O 0
was O 0
administered O 0
to O 0
reduce O 0
mean O 0
arterial O 0
pressure O 0
by O 0
30 O 0
% O 0
to O 0
70 O 0
% O 0
of O 0
control O 0
. O 0

Before O 0
, O 0
during O 0
and O 0
after O 0
induced O 0
hypotension B-Disease 0
, O 0
we O 0
measured O 0
major O 0
cardiovascular O 0
parameters O 0
. O 0

Hypotension B-Disease 0
induced O 0
by O 0
ATP B-Chemical 0
was O 0
accompanied O 0
by O 0
significant O 0
decreases O 0
in O 0
mean O 0
pulmonary O 0
arterial O 0
pressure O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
central O 0
venous O 0
pressure O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
left O 0
ventricular O 0
end O 0
- O 0
diastolic O 0
pressure O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
total O 0
peripheral O 0
resistance O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
rate O 0
pressure O 0
product O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
total O 0
body O 0
oxygen B-Chemical 0
consumption O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
, O 0
and O 0
heart O 0
rate O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
; O 0
all O 0
these O 0
variables O 0
returned O 0
normal O 0
within O 0
30 O 0
min O 0
after O 0
ATP B-Chemical 0
was O 0
stopped O 0
. O 0

Cardiac O 0
output O 0
did O 0
not O 0
change O 0
. O 0

During O 0
hypotension B-Disease 0
produced O 0
by O 0
SNP B-Chemical 0
similar O 0
decreases O 0
were O 0
observed O 0
in O 0
mean O 0
pulmonary O 0
arterial O 0
pressure O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
, O 0
central O 0
venous O 0
pressure O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
left O 0
ventricular O 0
end O 0
- O 0
diastolic O 0
pressure O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
, O 0
total O 0
peripheral O 0
resistance O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
rate O 0
pressure O 0
product O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
and O 0
oxygen B-Chemical 0
content O 0
difference O 0
between O 0
arterial O 0
and O 0
mixed O 0
venous O 0
blood O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
, O 0
while O 0
heart O 0
rate O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
and O 0
cardiac O 0
output O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
were O 0
increased O 0
. O 0

Recoveries O 0
of O 0
heart O 0
rate O 0
and O 0
left O 0
ventricular O 0
end O 0
- O 0
diastolic O 0
pressure O 0
were O 0
not O 0
shown O 0
within O 0
60 O 0
min O 0
after O 0
SNP B-Chemical 0
had O 0
been O 0
stopped O 0
. O 0

Both O 0
ATP B-Chemical 0
and O 0
SNP B-Chemical 0
should O 0
act O 0
on O 0
the O 0
pacemaker O 0
tissue O 0
of O 0
the O 0
heart O 0
. O 0

Comparative O 0
study O 0
: O 0
Endografine B-Chemical 0
( O 0
diatrizoate B-Chemical 0
) O 0
, O 0
Vasurix B-Chemical 0
polyvidone I-Chemical 0
( O 0
acetrizoate B-Chemical 0
) O 0
, O 0
Dimer B-Chemical 0
- I-Chemical 0
X I-Chemical 0
( O 0
iocarmate B-Chemical 0
) O 0
and O 0
Hexabrix B-Chemical 0
( O 0
ioxaglate B-Chemical 0
) O 0
in O 0
hysterosalpingography O 0
. O 0

Side O 0
effects O 0
of O 0
hysterosalpingography O 0
with O 0
Dimer B-Chemical 0
- I-Chemical 0
X I-Chemical 0
, O 0
Hexabrix B-Chemical 0
, O 0
Vasurix B-Chemical 0
polyvidone I-Chemical 0
and O 0
Endografine B-Chemical 0
in O 0
142 O 0
consecutive O 0
patients O 0
, O 0
receiving O 0
one O 0
of O 0
the O 0
four O 0
tested O 0
media O 0
were O 0
evaluated O 0
from O 0
replies O 0
to O 0
postal O 0
questionnaires O 0
. O 0

The O 0
Dimer B-Chemical 0
- I-Chemical 0
X I-Chemical 0
group O 0
had O 0
a O 0
higher O 0
incidence O 0
of O 0
nausea B-Disease 0
and O 0
dizziness B-Disease 0
. O 0

The O 0
Endografine B-Chemical 0
group O 0
had O 0
a O 0
higher O 0
incidence O 0
of O 0
abdominal B-Disease 0
pain I-Disease 0
. O 0

These O 0
differences O 0
occur O 0
especially O 0
in O 0
the O 0
age O 0
groups O 0
under O 0
30 O 0
years O 0
. O 0

Hexabrix B-Chemical 0
and O 0
Vasurix B-Chemical 0
polyvidone I-Chemical 0
are O 0
considered O 0
the O 0
best O 0
contrast B-Chemical 0
media I-Chemical 0
for O 0
hysterosalpingography O 0
and O 0
perhaps O 0
because O 0
of O 0
its O 0
low O 0
toxicity B-Disease 0
Hexabrix B-Chemical 0
should O 0
be O 0
preferred O 0
. O 0

Post O 0
- O 0
suxamethonium B-Chemical 0
pains B-Disease 0
in O 0
Nigerian O 0
surgical O 0
patients O 0
. O 0

Contrary O 0
to O 0
an O 0
earlier O 0
report O 0
by O 0
Coxon O 0
, O 0
scoline B-Chemical 0
pain B-Disease 0
occurs O 0
in O 0
African O 0
negroes O 0
. O 0

Its O 0
incidence O 0
was O 0
determined O 0
in O 0
a O 0
prospective O 0
study O 0
involving O 0
a O 0
total O 0
of O 0
100 O 0
Nigerian O 0
patients O 0
( O 0
50 O 0
out O 0
- O 0
patients O 0
and O 0
50 O 0
in O 0
- O 0
patients O 0
) O 0
. O 0

About O 0
62 O 0
% O 0
of O 0
the O 0
out O 0
- O 0
patients O 0
developed O 0
scoline B-Chemical 0
pain B-Disease 0
as O 0
compared O 0
with O 0
about O 0
26 O 0
% O 0
among O 0
the O 0
in O 0
- O 0
patients O 0
. O 0

The O 0
abolition O 0
of O 0
muscle O 0
fasciculations B-Disease 0
( O 0
by O 0
0 O 0
. O 0
075mg O 0
/ O 0
kg O 0
dose O 0
of O 0
Fazadinium B-Chemical 0
) O 0
did O 0
not O 0
influence O 0
the O 0
occurrence O 0
of O 0
scoline B-Chemical 0
pain B-Disease 0
. O 0

Neither O 0
the O 0
type O 0
of O 0
induction O 0
agent O 0
( O 0
Althesin B-Chemical 0
or O 0
Thiopentone B-Chemical 0
) O 0
nor O 0
the O 0
salt O 0
preparation O 0
of O 0
suxamethonium B-Chemical 0
used O 0
( O 0
chloride B-Chemical 0
or O 0
bromide B-Chemical 0
) O 0
, O 0
affected O 0
the O 0
incidence O 0
of O 0
scoline B-Chemical 0
pain B-Disease 0
. O 0

Invasive O 0
carcinoma B-Disease 0
of I-Disease 0
the I-Disease 0
renal I-Disease 0
pelvis I-Disease 0
following O 0
cyclophosphamide B-Chemical 0
therapy O 0
for O 0
nonmalignant O 0
disease O 0
. O 0

A O 0
47 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
right O 0
hydroureteronephrosis B-Disease 0
due O 0
to O 0
ureterovesical O 0
junction O 0
obstruction O 0
had O 0
gross O 0
hematuria B-Disease 0
after O 0
being O 0
treated O 0
for O 0
five O 0
years O 0
wtih O 0
cyclophosphamide B-Chemical 0
for O 0
cerebral B-Disease 0
vasculitis I-Disease 0
. O 0

A O 0
right O 0
nephroureterectomy O 0
was O 0
required O 0
for O 0
control O 0
of O 0
bleeding B-Disease 0
. O 0

The O 0
pathology O 0
specimen O 0
contained O 0
clinically O 0
occult O 0
invasive O 0
carcinoma B-Disease 0
of I-Disease 0
the I-Disease 0
renal I-Disease 0
pelvis I-Disease 0
. O 0

Although O 0
the O 0
ability O 0
of O 0
cyclophosphamide B-Chemical 0
to O 0
cause O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
and O 0
urine O 0
cytologic O 0
abnormalities O 0
indistinguishable O 0
from O 0
high O 0
grade O 0
carcinoma B-Disease 0
is O 0
well O 0
known O 0
, O 0
it O 0
is O 0
less O 0
widely O 0
appreciated O 0
that O 0
it O 0
is O 0
also O 0
associated O 0
with O 0
carcinoma B-Disease 0
of I-Disease 0
the I-Disease 0
urinary I-Disease 0
tract I-Disease 0
. O 0

Twenty O 0
carcinomas B-Disease 0
of I-Disease 0
the I-Disease 0
urinary I-Disease 0
bladder I-Disease 0
and O 0
one O 0
carcinoma B-Disease 0
of I-Disease 0
the I-Disease 0
prostate I-Disease 0
have O 0
been O 0
reported O 0
in O 0
association O 0
with O 0
its O 0
use O 0
. O 0

The O 0
present O 0
case O 0
is O 0
the O 0
first O 0
carcinoma B-Disease 0
of I-Disease 0
the I-Disease 0
renal I-Disease 0
pelvis I-Disease 0
reported O 0
in O 0
association O 0
with O 0
cyclophosphamide B-Chemical 0
treatment O 0
. O 0

It O 0
is O 0
the O 0
third O 0
urinary B-Disease 0
tract I-Disease 0
cancer I-Disease 0
reported O 0
in O 0
association O 0
with O 0
cyclophosphamide B-Chemical 0
treatment O 0
for O 0
nonmalignant O 0
disease O 0
. O 0

The O 0
association O 0
of O 0
the O 0
tumor B-Disease 0
with O 0
preexisting O 0
hydroureteronephrosis B-Disease 0
suggests O 0
that O 0
stasis O 0
prolonged O 0
and O 0
intensified O 0
exposure O 0
of O 0
upper O 0
urinary O 0
tract O 0
epithelium O 0
to O 0
cyclophosphamide B-Chemical 0
. O 0

Patients O 0
who O 0
are O 0
candidates O 0
for O 0
long O 0
- O 0
term O 0
cyclophosphamide B-Chemical 0
treatment O 0
should O 0
be O 0
routinely O 0
evaluated O 0
for O 0
obstructive B-Disease 0
uropathy I-Disease 0
. O 0

Medial O 0
changes O 0
in O 0
arterial O 0
spasm B-Disease 0
induced O 0
by O 0
L B-Chemical 0
- I-Chemical 0
norepinephrine I-Chemical 0
. O 0

In O 0
normal O 0
rats O 0
, O 0
the O 0
media O 0
of O 0
small O 0
arteries O 0
( O 0
0 O 0
. O 0
4 O 0
- O 0
- O 0
0 O 0
. O 0
2 O 0
mm O 0
in O 0
diameter O 0
) O 0
previously O 0
was O 0
shown O 0
to O 0
contain O 0
intracellular O 0
vacuoles O 0
, O 0
identified O 0
ultrastructurally O 0
as O 0
herniations O 0
of O 0
one O 0
smooth O 0
muscle O 0
cell O 0
into O 0
another O 0
. O 0

The O 0
hypothesis O 0
that O 0
intense O 0
vasoconstriction O 0
would O 0
increase O 0
the O 0
number O 0
of O 0
such O 0
vacuoles O 0
has O 0
been O 0
tested O 0
. O 0

In O 0
the O 0
media O 0
of O 0
the O 0
saphenous O 0
artery O 0
and O 0
its O 0
distal O 0
branch O 0
, O 0
vasoconstriction O 0
induced O 0
by O 0
L B-Chemical 0
- I-Chemical 0
norepinephrine I-Chemical 0
produced O 0
many O 0
cell O 0
- O 0
to O 0
- O 0
cell O 0
hernias B-Disease 0
within O 0
15 O 0
minutes O 0
. O 0

At O 0
1 O 0
day O 0
their O 0
number O 0
was O 0
reduced O 0
to O 0
about O 0
1 O 0
/ O 0
10 O 0
of O 0
the O 0
original O 0
number O 0
. O 0

By O 0
7 O 0
days O 0
the O 0
vessel O 0
was O 0
almost O 0
restored O 0
to O 0
normal O 0
. O 0

Triple O 0
stimulation O 0
over O 0
1 O 0
day O 0
induced O 0
more O 0
severe O 0
changes O 0
in O 0
the O 0
media O 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
smooth O 0
muscle O 0
cells O 0
are O 0
susceptible O 0
to O 0
damage O 0
in O 0
the O 0
course O 0
of O 0
their O 0
specific O 0
function O 0
. O 0

The O 0
experimental O 0
data O 0
are O 0
discussed O 0
in O 0
relation O 0
to O 0
medial O 0
changes O 0
observed O 0
in O 0
other O 0
instances O 0
of O 0
arterial O 0
spasm B-Disease 0
. O 0

Endothelial O 0
changes O 0
that O 0
developed O 0
in O 0
the O 0
same O 0
experimental O 0
model O 0
were O 0
described O 0
in O 0
a O 0
previous O 0
paper O 0
. O 0

Bilateral O 0
retinal B-Disease 0
artery I-Disease 0
and I-Disease 0
choriocapillaris I-Disease 0
occlusion I-Disease 0
following O 0
the O 0
injection O 0
of O 0
long O 0
- O 0
acting O 0
corticosteroid B-Chemical 0
suspensions O 0
in O 0
combination O 0
with O 0
other O 0
drugs O 0
: O 0
I O 0
. O 0

Clinical O 0
studies O 0
. O 0

Two O 0
well O 0
- O 0
documented O 0
cases O 0
of O 0
bilateral O 0
retinal B-Disease 0
artery I-Disease 0
and I-Disease 0
choriocapillaris I-Disease 0
occlusions I-Disease 0
with O 0
blindness B-Disease 0
following O 0
head O 0
and O 0
neck O 0
soft O 0
- O 0
tissue O 0
injection O 0
with O 0
methylprednisolone B-Chemical 0
acetate I-Chemical 0
in O 0
combination O 0
with O 0
lidocaine B-Chemical 0
, O 0
epinephrine B-Chemical 0
, O 0
or O 0
penicillin B-Chemical 0
are O 0
reported O 0
. O 0

One O 0
case O 0
had O 0
only O 0
a O 0
unilateral O 0
injection O 0
. O 0

The O 0
acute O 0
observations O 0
included O 0
hazy O 0
sensorium O 0
, O 0
superior O 0
gaze O 0
palsy B-Disease 0
, O 0
pupillary B-Disease 0
abnormalities I-Disease 0
, O 0
and O 0
conjunctival O 0
hemorrhages B-Disease 0
with O 0
edema B-Disease 0
. O 0

Follow O 0
- O 0
up O 0
changes O 0
showed O 0
marked O 0
visual B-Disease 0
loss I-Disease 0
, O 0
constricted O 0
visual O 0
fields O 0
, O 0
optic O 0
nerve O 0
pallor O 0
, O 0
vascular O 0
attenuation O 0
, O 0
and O 0
chorioretinal B-Disease 0
atrophy I-Disease 0
. O 0

The O 0
literature O 0
is O 0
reviewed O 0
, O 0
and O 0
possible O 0
causes O 0
are O 0
discussed O 0
. O 0

Abnormalities O 0
of O 0
the O 0
pupil O 0
and O 0
visual O 0
- O 0
evoked O 0
potential O 0
in O 0
quinine B-Chemical 0
amblyopia B-Disease 0
. O 0

Total O 0
blindness B-Disease 0
with O 0
a O 0
transient O 0
tonic B-Disease 0
pupillary I-Disease 0
response O 0
, O 0
denervation O 0
supersensitivity O 0
, O 0
and O 0
abnormal O 0
visual O 0
- O 0
evoked O 0
potentials O 0
developed O 0
in O 0
a O 0
54 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
after O 0
the O 0
use O 0
of O 0
quinine B-Chemical 0
sulfate I-Chemical 0
for O 0
leg B-Disease 0
cramps I-Disease 0
. O 0

He O 0
later O 0
recovered O 0
normal O 0
visual O 0
acuity O 0
. O 0

A O 0
transient O 0
tonic B-Disease 0
pupillary I-Disease 0
response O 0
, O 0
denervation O 0
supersensitivity O 0
, O 0
and O 0
abnormal O 0
visual O 0
- O 0
evoked O 0
potentials O 0
in O 0
quinine B-Chemical 0
toxicity B-Disease 0
, O 0
to O 0
our O 0
knowledge O 0
, O 0
have O 0
not O 0
been O 0
previously O 0
reported O 0
. O 0

Suxamethonium B-Chemical 0
- O 0
induced O 0
jaw B-Disease 0
stiffness I-Disease 0
and O 0
myalgia B-Disease 0
associated O 0
with O 0
atypical O 0
cholinesterase O 0
: O 0
case O 0
report O 0
. O 0

An O 0
11 O 0
- O 0
year O 0
- O 0
old O 0
boy O 0
was O 0
given O 0
halothane B-Chemical 0
, O 0
nitrous B-Chemical 0
oxide I-Chemical 0
and O 0
oxygen B-Chemical 0
, O 0
pancuronium B-Chemical 0
0 O 0
. O 0
4 O 0
mg O 0
and O 0
suxamethonium B-Chemical 0
100 O 0
mg O 0
for O 0
induction O 0
of O 0
anaesthesia O 0
. O 0

In O 0
response O 0
to O 0
this O 0
a O 0
marked O 0
jaw B-Disease 0
stiffness I-Disease 0
occurred O 0
which O 0
lasted O 0
for O 0
two O 0
minutes O 0
and O 0
the O 0
anaesthesia O 0
were O 0
terminated O 0
. O 0

Four O 0
hours O 0
of O 0
apnoea B-Disease 0
ensued O 0
and O 0
he O 0
suffered O 0
generalized O 0
severe O 0
myalgia B-Disease 0
lasting O 0
for O 0
one O 0
week O 0
. O 0

He O 0
was O 0
found O 0
to O 0
have O 0
atypical O 0
plasma O 0
cholinesterase O 0
with O 0
a O 0
dibucaine B-Chemical 0
number O 0
of O 0
12 O 0
, O 0
indicating O 0
homozygocity O 0
. O 0

This O 0
was O 0
verified O 0
by O 0
study O 0
of O 0
the O 0
family O 0
. O 0

The O 0
case O 0
shows O 0
that O 0
prolonged B-Disease 0
jaw I-Disease 0
rigidity I-Disease 0
and O 0
myalgia B-Disease 0
may O 0
occur O 0
after O 0
suxamethonium B-Chemical 0
in O 0
patients O 0
with O 0
atypical O 0
cholinesterase O 0
despite O 0
pretreatment O 0
with O 0
pancuronium B-Chemical 0
. O 0

Indomethacin B-Chemical 0
- O 0
induced O 0
hyperkalemia B-Disease 0
in O 0
three O 0
patients O 0
with O 0
gouty B-Disease 0
arthritis I-Disease 0
. O 0

We O 0
describe O 0
three O 0
patients O 0
in O 0
whom O 0
severe O 0
, O 0
life O 0
- O 0
threatening O 0
hyperkalemia B-Disease 0
and O 0
renal B-Disease 0
insufficiency I-Disease 0
developed O 0
after O 0
treatment O 0
of O 0
acute O 0
gouty B-Disease 0
arthritis I-Disease 0
with O 0
indomethacin B-Chemical 0
. O 0

This O 0
complication O 0
may O 0
result O 0
from O 0
an O 0
inhibition O 0
of O 0
prostaglandin B-Chemical 0
synthesis O 0
and O 0
consequent O 0
hyporeninemic B-Disease 0
hypoaidosteronism I-Disease 0
. O 0

Careful O 0
attention O 0
to O 0
renal O 0
function O 0
and O 0
potassium B-Chemical 0
balance O 0
in O 0
patients O 0
receiving O 0
indomethacin B-Chemical 0
or O 0
other O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
agents O 0
, O 0
particularly O 0
in O 0
those O 0
patients O 0
with O 0
diabetes B-Disease 0
mellitus I-Disease 0
or O 0
preexisting O 0
renal B-Disease 0
disease I-Disease 0
, O 0
will O 0
help O 0
prevent O 0
this O 0
potentially O 0
serious O 0
complication O 0
. O 0

Etomidate B-Chemical 0
: O 0
a O 0
foreshortened O 0
clinical O 0
trial O 0
. O 0

A O 0
clinical O 0
evaluation O 0
of O 0
etomidate B-Chemical 0
for O 0
outpatient O 0
cystoscopy O 0
was O 0
embarked O 0
upon O 0
. O 0

Unpremedicated O 0
patients O 0
were O 0
given O 0
fentanyl B-Chemical 0
1 O 0
microgram O 0
/ O 0
kg O 0
followed O 0
by O 0
etomidate B-Chemical 0
0 O 0
. O 0
3 O 0
mg O 0
/ O 0
kg O 0
. O 0

Anaesthesia O 0
was O 0
maintained O 0
with O 0
intermittent O 0
etomidate B-Chemical 0
in O 0
2 O 0
- O 0
4 O 0
mg O 0
doses O 0
. O 0

Patients O 0
were O 0
interviewed O 0
personally O 0
later O 0
the O 0
same O 0
day O 0
, O 0
and O 0
by O 0
questionnaire O 0
three O 0
to O 0
four O 0
weeks O 0
later O 0
. O 0

The O 0
trial O 0
was O 0
discontinued O 0
after O 0
20 O 0
cases O 0
because O 0
of O 0
an O 0
unacceptable O 0
incidence O 0
of O 0
side O 0
effects O 0
. O 0

Venous O 0
pain B-Disease 0
occurred O 0
in O 0
68 O 0
% O 0
of O 0
patients O 0
and O 0
50 O 0
% O 0
had O 0
redness O 0
, O 0
pain B-Disease 0
or O 0
swelling B-Disease 0
related O 0
to O 0
the O 0
injection O 0
site O 0
, O 0
in O 0
some O 0
cases O 0
lasting O 0
up O 0
to O 0
three O 0
weeks O 0
after O 0
anaesthesia O 0
. O 0

Skeletal O 0
movements O 0
occurred O 0
in O 0
50 O 0
% O 0
of O 0
patients O 0
; O 0
30 O 0
% O 0
experienced O 0
respiratory B-Disease 0
upset I-Disease 0
, O 0
one O 0
sufficiently O 0
severe O 0
to O 0
necessitate O 0
abandoning O 0
the O 0
technique O 0
. O 0

Nausea B-Disease 0
and O 0
vomiting B-Disease 0
occurred O 0
in O 0
40 O 0
% O 0
and O 0
25 O 0
% O 0
had O 0
disturbing O 0
emergence O 0
psychoses B-Disease 0
. O 0

Levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
are O 0
improved O 0
by O 0
fluoxetine B-Chemical 0
. O 0

We O 0
evaluated O 0
the O 0
severity O 0
of O 0
motor B-Disease 0
disability I-Disease 0
and O 0
dyskinesias B-Disease 0
in O 0
seven O 0
levodopa B-Chemical 0
- O 0
responsive O 0
patients O 0
with O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
after O 0
an O 0
acute O 0
challenge O 0
with O 0
the O 0
mixed O 0
dopamine B-Chemical 0
agonist O 0
, O 0
apomorphine B-Chemical 0
, O 0
before O 0
and O 0
after O 0
the O 0
administration O 0
of O 0
fluoxetine B-Chemical 0
( O 0
20 O 0
mg O 0
twice O 0
per O 0
day O 0
) O 0
for O 0
11 O 0
+ O 0
/ O 0
- O 0
1 O 0
days O 0
. O 0

After O 0
fluoxetine B-Chemical 0
treatment O 0
, O 0
there O 0
was O 0
a O 0
significant O 0
47 O 0
% O 0
improvement O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
of O 0
apomorphine B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
without O 0
modification O 0
of O 0
parkinsonian B-Disease 0
motor B-Disease 0
disability I-Disease 0
. O 0

The O 0
dyskinesias B-Disease 0
were O 0
reduced O 0
predominantly O 0
in O 0
the O 0
lower O 0
limbs O 0
during O 0
the O 0
onset O 0
and O 0
disappearance O 0
of O 0
dystonic B-Disease 0
dyskinesias I-Disease 0
( O 0
onset O 0
- O 0
and O 0
end O 0
- O 0
of O 0
- O 0
dose O 0
dyskinesias B-Disease 0
) O 0
and O 0
in O 0
the O 0
upper O 0
limbs O 0
during O 0
choreic B-Disease 0
mid I-Disease 0
- I-Disease 0
dose I-Disease 0
dyskinesias I-Disease 0
. O 0

The O 0
results O 0
suggest O 0
that O 0
increased O 0
brain O 0
serotoninergic O 0
transmission O 0
with O 0
fluoxetine B-Chemical 0
may O 0
reduce O 0
levodopa B-Chemical 0
- O 0
or O 0
dopamine B-Chemical 0
agonist O 0
- O 0
induced O 0
dyskinesias B-Disease 0
without O 0
aggravating O 0
parkinsonian B-Disease 0
motor B-Disease 0
disability I-Disease 0
. O 0

A O 0
large O 0
population O 0
- O 0
based O 0
follow O 0
- O 0
up O 0
study O 0
of O 0
trimethoprim B-Chemical 0
- I-Chemical 0
sulfamethoxazole I-Chemical 0
, O 0
trimethoprim B-Chemical 0
, O 0
and O 0
cephalexin B-Chemical 0
for O 0
uncommon O 0
serious O 0
drug B-Disease 0
toxicity I-Disease 0
. O 0

We O 0
conducted O 0
a O 0
population O 0
- O 0
based O 0
45 O 0
- O 0
day O 0
follow O 0
- O 0
up O 0
study O 0
of O 0
232 O 0
, O 0
390 O 0
people O 0
who O 0
were O 0
prescribed O 0
trimethoprim B-Chemical 0
- I-Chemical 0
sulfamethoxazole I-Chemical 0
( O 0
TMP B-Chemical 0
- I-Chemical 0
SMZ I-Chemical 0
) O 0
, O 0
266 O 0
, O 0
951 O 0
prescribed O 0
trimethoprim B-Chemical 0
alone O 0
, O 0
and O 0
196 O 0
, O 0
397 O 0
prescribed O 0
cephalexin B-Chemical 0
, O 0
to O 0
estimate O 0
the O 0
risk O 0
of O 0
serious O 0
liver B-Disease 0
, I-Disease 0
blood I-Disease 0
, I-Disease 0
skin I-Disease 0
, I-Disease 0
and I-Disease 0
renal I-Disease 0
disorders I-Disease 0
resulting O 0
in O 0
referral O 0
or O 0
hospitalization O 0
associated O 0
with O 0
these O 0
drugs O 0
. O 0

The O 0
results O 0
were O 0
based O 0
on O 0
information O 0
recorded O 0
on O 0
office O 0
computers O 0
by O 0
selected O 0
general O 0
practitioners O 0
in O 0
the O 0
United O 0
Kingdom O 0
, O 0
together O 0
with O 0
a O 0
review O 0
of O 0
clinical O 0
records O 0
. O 0

The O 0
risk O 0
of O 0
clinically O 0
important O 0
idiopathic O 0
liver B-Disease 0
disease I-Disease 0
was O 0
similar O 0
for O 0
persons O 0
prescribed O 0
TMP B-Chemical 0
- I-Chemical 0
SMZ I-Chemical 0
( O 0
5 O 0
. O 0
2 O 0
/ O 0
100 O 0
, O 0
000 O 0
) O 0
and O 0
those O 0
prescribed O 0
trimethoprim B-Chemical 0
alone O 0
( O 0
3 O 0
. O 0
8 O 0
/ O 0
100 O 0
, O 0
000 O 0
) O 0
. O 0

The O 0
risk O 0
for O 0
those O 0
prescribed O 0
cephalexin B-Chemical 0
was O 0
somewhat O 0
lower O 0
( O 0
2 O 0
. O 0
0 O 0
/ O 0
100 O 0
, O 0
000 O 0
) O 0
. O 0

Only O 0
five O 0
patients O 0
experienced O 0
blood O 0
disorders O 0
, O 0
one O 0
of O 0
whom O 0
was O 0
exposed O 0
to O 0
TMP B-Chemical 0
- I-Chemical 0
SMZ I-Chemical 0
; O 0
of O 0
seven O 0
with O 0
erythema B-Disease 0
multiforme I-Disease 0
and O 0
Stevens B-Disease 0
- I-Disease 0
Johnson I-Disease 0
syndrome I-Disease 0
, O 0
four O 0
were O 0
exposed O 0
to O 0
TMP B-Chemical 0
- I-Chemical 0
SMZ I-Chemical 0
. O 0

The O 0
one O 0
case O 0
of O 0
toxic B-Disease 0
epidermal I-Disease 0
necrolysis I-Disease 0
occurred O 0
in O 0
a O 0
patient O 0
who O 0
took O 0
cephalexin B-Chemical 0
. O 0

Finally O 0
, O 0
only O 0
five O 0
cases O 0
of O 0
acute O 0
parenchymal O 0
renal B-Disease 0
disease I-Disease 0
occurred O 0
, O 0
none O 0
likely O 0
to O 0
be O 0
caused O 0
by O 0
a O 0
study O 0
drug O 0
. O 0

We O 0
conclude O 0
that O 0
the O 0
risk O 0
of O 0
the O 0
serious O 0
diseases O 0
studied O 0
is O 0
small O 0
for O 0
the O 0
three O 0
agents O 0
, O 0
and O 0
compares O 0
reasonably O 0
with O 0
the O 0
risk O 0
for O 0
many O 0
other O 0
antibiotics O 0
. O 0

Clinical O 0
safety O 0
of O 0
lidocaine B-Chemical 0
in O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

STUDY O 0
OBJECTIVE O 0
: O 0
To O 0
evaluate O 0
the O 0
safety O 0
of O 0
lidocaine B-Chemical 0
in O 0
the O 0
setting O 0
of O 0
cocaine B-Chemical 0
- O 0
induced O 0
myocardial B-Disease 0
infarction I-Disease 0
( O 0
MI B-Disease 0
) O 0
. O 0

DESIGN O 0
: O 0
A O 0
retrospective O 0
, O 0
multicenter O 0
study O 0
. O 0

SETTING O 0
: O 0
Twenty O 0
- O 0
nine O 0
university O 0
, O 0
university O 0
- O 0
affiliated O 0
, O 0
or O 0
community O 0
hospitals O 0
during O 0
a O 0
6 O 0
- O 0
year O 0
period O 0
( O 0
total O 0
of O 0
117 O 0
cumulative O 0
hospital O 0
- O 0
years O 0
) O 0
. O 0

PARTICIPANTS O 0
: O 0
Patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
MI B-Disease 0
who O 0
received O 0
lidocaine B-Chemical 0
in O 0
the O 0
emergency O 0
department O 0
. O 0

RESULTS O 0
: O 0
Of O 0
29 O 0
patients O 0
who O 0
received O 0
lidocaine B-Chemical 0
in O 0
the O 0
setting O 0
of O 0
cocaine B-Chemical 0
- O 0
associated O 0
MI B-Disease 0
, O 0
no O 0
patient O 0
died O 0
; O 0
exhibited O 0
bradydysrhythmias B-Disease 0
, O 0
ventricular B-Disease 0
tachycardia I-Disease 0
, O 0
or O 0
ventricular B-Disease 0
fibrillation I-Disease 0
; O 0
or O 0
experienced O 0
seizures B-Disease 0
after O 0
administration O 0
of O 0
lidocaine B-Chemical 0
( O 0
95 O 0
% O 0
confidence O 0
interval O 0
, O 0
0 O 0
% O 0
to O 0
11 O 0
% O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
Despite O 0
theoretical O 0
concerns O 0
that O 0
lidocaine B-Chemical 0
may O 0
enhance O 0
cocaine B-Chemical 0
toxicity B-Disease 0
, O 0
the O 0
use O 0
of O 0
lidocaine B-Chemical 0
in O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
MI B-Disease 0
was O 0
not O 0
associated O 0
with O 0
significant O 0
cardiovascular B-Disease 0
or I-Disease 0
central I-Disease 0
nervous I-Disease 0
system I-Disease 0
toxicity I-Disease 0
. O 0

Experimental O 0
progressive O 0
muscular B-Disease 0
dystrophy I-Disease 0
and O 0
its O 0
treatment O 0
with O 0
high O 0
doses O 0
anabolizing O 0
agents O 0
. O 0

We O 0
are O 0
still O 0
a O 0
long O 0
way O 0
from O 0
discovering O 0
an O 0
unequivocal O 0
pathogenetic O 0
interpretation O 0
of O 0
progressive O 0
muscular B-Disease 0
dystrophy I-Disease 0
in O 0
man O 0
. O 0

Noteworthy O 0
efforts O 0
have O 0
been O 0
made O 0
in O 0
the O 0
experimental O 0
field O 0
; O 0
a O 0
recessive O 0
autosomic O 0
form O 0
found O 0
in O 0
the O 0
mouse O 0
seems O 0
to O 0
bear O 0
the O 0
closest O 0
resemblance O 0
to O 0
the O 0
human O 0
form O 0
from O 0
the O 0
genetic O 0
point O 0
of O 0
view O 0
. O 0

Myopathy B-Disease 0
due O 0
to O 0
lack O 0
of O 0
vitamin B-Chemical 0
E I-Chemical 0
and O 0
myopathy B-Disease 0
induced O 0
by O 0
certain O 0
viruses O 0
have O 0
much O 0
in O 0
common O 0
anatomically O 0
and O 0
pathologically O 0
with O 0
the O 0
human O 0
form O 0
. O 0

The O 0
authors O 0
induced O 0
myodystrophy B-Disease 0
in O 0
the O 0
rat O 0
by O 0
giving O 0
it O 0
a O 0
diet O 0
lacking O 0
in O 0
vitamin B-Chemical 0
E I-Chemical 0
. O 0

The O 0
pharmacological O 0
characteristics O 0
of O 0
vitamin B-Chemical 0
E I-Chemical 0
and O 0
the O 0
degenerative O 0
changes O 0
brought O 0
about O 0
by O 0
its O 0
deficiency O 0
, O 0
especially O 0
in O 0
the O 0
muscles O 0
, O 0
are O 0
illustrated O 0
. O 0

It O 0
is O 0
thus O 0
confirmed O 0
that O 0
the O 0
histological O 0
characteristics O 0
of O 0
myopathic B-Disease 0
rat O 0
muscle O 0
induced O 0
experimentally O 0
are O 0
extraordinarily O 0
similar O 0
to O 0
those O 0
of O 0
human O 0
myopathy B-Disease 0
as O 0
confirmed O 0
during O 0
biopsies O 0
performed O 0
at O 0
the O 0
Orthopaedic O 0
Traumatological O 0
Centre O 0
, O 0
Florence O 0
. O 0

The O 0
encouraging O 0
results O 0
obtained O 0
in O 0
various O 0
authoratative O 0
departments O 0
in O 0
myopathic B-Disease 0
patients O 0
by O 0
using O 0
anabolizing O 0
steroids B-Chemical 0
have O 0
encouraged O 0
the O 0
authors O 0
to O 0
investigate O 0
the O 0
beneficial O 0
effects O 0
of O 0
one O 0
anabolizing O 0
agent O 0
( O 0
Dianabol B-Chemical 0
, O 0
CIBA B-Chemical 0
) O 0
at O 0
high O 0
doses O 0
in O 0
rats O 0
rendered O 0
myopathic B-Disease 0
by O 0
a O 0
diet O 0
deficient O 0
in O 0
vitamin B-Chemical 0
E I-Chemical 0
. O 0

In O 0
this O 0
way O 0
they O 0
obtained O 0
appreciable O 0
changes O 0
in O 0
body O 0
weight O 0
( O 0
increased O 0
from O 0
50 O 0
to O 0
70 O 0
g O 0
after O 0
forty O 0
days O 0
at O 0
a O 0
dose O 0
of O 0
5 O 0
mg O 0
per O 0
day O 0
of O 0
anabolizing O 0
agent O 0
) O 0
, O 0
but O 0
most O 0
of O 0
all O 0
they O 0
found O 0
histological O 0
changes O 0
due O 0
to O 0
" O 0
regenerative O 0
" O 0
changes O 0
in O 0
the O 0
muscle O 0
tissue O 0
, O 0
which O 0
however O 0
maintained O 0
its O 0
myopathic B-Disease 0
characteristics O 0
in O 0
the O 0
control O 0
animals O 0
that O 0
were O 0
not O 0
treated O 0
with O 0
the O 0
anabolizing O 0
agent O 0
. O 0

The O 0
authors O 0
conclude O 0
by O 0
affirming O 0
the O 0
undoubted O 0
efficacy O 0
of O 0
the O 0
anabolizing O 0
steroids B-Chemical 0
in O 0
experimental O 0
myopathic B-Disease 0
disease I-Disease 0
, O 0
but O 0
they O 0
have O 0
reservations O 0
as O 0
to O 0
the O 0
transfer O 0
of O 0
the O 0
results O 0
into O 0
the O 0
human O 0
field O 0
, O 0
where O 0
high O 0
dosage O 0
cannot O 0
be O 0
carried O 0
out O 0
continuously O 0
because O 0
of O 0
the O 0
effects O 0
of O 0
the O 0
drug O 0
on O 0
virility O 0
; O 0
because O 0
the O 0
tissue O 0
injury O 0
too O 0
often O 0
occurs O 0
at O 0
an O 0
irreversible O 0
stage O 0
vis O 0
- O 0
a O 0
- O 0
vis O 0
the O 0
" O 0
regeneration O 0
" O 0
of O 0
the O 0
muscle O 0
tissue O 0
; O 0
and O 0
finally O 0
because O 0
the O 0
dystrophic O 0
injurious O 0
agent O 0
is O 0
certainly O 0
not O 0
the O 0
lack O 0
of O 0
vitamin B-Chemical 0
E I-Chemical 0
but O 0
something O 0
as O 0
yet O 0
unknown O 0
. O 0

Paclitaxel B-Chemical 0
3 O 0
- O 0
hour O 0
infusion O 0
given O 0
alone O 0
and O 0
combined O 0
with O 0
carboplatin B-Chemical 0
: O 0
preliminary O 0
results O 0
of O 0
dose O 0
- O 0
escalation O 0
trials O 0
. O 0

Paclitaxel B-Chemical 0
( O 0
Taxol B-Chemical 0
; O 0
Bristol O 0
- O 0
Myers O 0
Squibb O 0
Company O 0
, O 0
Princeton O 0
, O 0
NJ O 0
) O 0
by O 0
3 O 0
- O 0
hour O 0
infusion O 0
was O 0
combined O 0
with O 0
carboplatin B-Chemical 0
in O 0
a O 0
phase O 0
I O 0
/ O 0
II O 0
study O 0
directed O 0
to O 0
patients O 0
with O 0
non B-Disease 0
- I-Disease 0
small I-Disease 0
cell I-Disease 0
lung I-Disease 0
cancer I-Disease 0
. O 0

Carboplatin B-Chemical 0
was O 0
given O 0
at O 0
a O 0
fixed O 0
target O 0
area O 0
under O 0
the O 0
concentration O 0
- O 0
time O 0
curve O 0
of O 0
6 O 0
. O 0
0 O 0
by O 0
the O 0
Calvert O 0
formula O 0
, O 0
whereas O 0
paclitaxel B-Chemical 0
was O 0
escalated O 0
in O 0
patient O 0
cohorts O 0
from O 0
150 O 0
mg O 0
/ O 0
m2 O 0
( O 0
dose O 0
level O 0
I O 0
) O 0
to O 0
175 O 0
, O 0
200 O 0
, O 0
225 O 0
, O 0
and O 0
250 O 0
mg O 0
/ O 0
m2 O 0
. O 0

The O 0
225 O 0
mg O 0
/ O 0
m2 O 0
level O 0
was O 0
expanded O 0
for O 0
the O 0
phase O 0
II O 0
study O 0
since O 0
the O 0
highest O 0
level O 0
achieved O 0
( O 0
250 O 0
mg O 0
/ O 0
m2 O 0
) O 0
required O 0
modification O 0
because O 0
of O 0
nonhematologic O 0
toxicities B-Disease 0
( O 0
arthralgia B-Disease 0
and O 0
sensory B-Disease 0
neuropathy I-Disease 0
) O 0
. O 0

Therapeutic O 0
effects O 0
were O 0
noted O 0
at O 0
all O 0
dose O 0
levels O 0
, O 0
with O 0
objective O 0
responses O 0
in O 0
17 O 0
( O 0
two O 0
complete O 0
and O 0
15 O 0
partial O 0
regressions O 0
) O 0
of O 0
41 O 0
previously O 0
untreated O 0
patients O 0
. O 0

Toxicities B-Disease 0
were O 0
compared O 0
with O 0
a O 0
cohort O 0
of O 0
patients O 0
in O 0
a O 0
phase O 0
I O 0
trial O 0
of O 0
paclitaxel B-Chemical 0
alone O 0
at O 0
identical O 0
dose O 0
levels O 0
. O 0

Carboplatin B-Chemical 0
did O 0
not O 0
appear O 0
to O 0
add O 0
to O 0
the O 0
hematologic B-Disease 0
toxicities I-Disease 0
observed O 0
, O 0
and O 0
the O 0
paclitaxel B-Chemical 0
/ O 0
carboplatin B-Chemical 0
combination O 0
could O 0
be O 0
dosed O 0
every O 0
3 O 0
weeks O 0
. O 0

The O 0
dose O 0
- O 0
dependent O 0
effect O 0
of O 0
misoprostol B-Chemical 0
on O 0
indomethacin B-Chemical 0
- O 0
induced O 0
renal B-Disease 0
dysfunction I-Disease 0
in O 0
well O 0
compensated O 0
cirrhosis B-Disease 0
. O 0

Misoprostol B-Chemical 0
( O 0
200 O 0
micrograms O 0
) O 0
has O 0
been O 0
shown O 0
to O 0
acutely O 0
counteract O 0
the O 0
indomethacin B-Chemical 0
- O 0
induced O 0
renal B-Disease 0
dysfunction I-Disease 0
in O 0
well O 0
compensated O 0
cirrhotic B-Disease 0
patients O 0
. O 0

The O 0
aim O 0
of O 0
this O 0
study O 0
was O 0
to O 0
determine O 0
if O 0
the O 0
prophylactic O 0
value O 0
of O 0
misoprostol B-Chemical 0
was O 0
dose O 0
- O 0
dependent O 0
. O 0

Parameters O 0
of O 0
renal O 0
hemodynamics O 0
and O 0
tubular O 0
sodium B-Chemical 0
and O 0
water O 0
handling O 0
were O 0
assessed O 0
by O 0
clearance O 0
techniques O 0
in O 0
26 O 0
well O 0
compensated O 0
cirrhotic B-Disease 0
patients O 0
before O 0
and O 0
after O 0
an O 0
oral O 0
combination O 0
of O 0
50 O 0
mg O 0
of O 0
indomethacin B-Chemical 0
and O 0
various O 0
doses O 0
of O 0
misoprostol B-Chemical 0
. O 0

The O 0
200 O 0
- O 0
micrograms O 0
dose O 0
was O 0
able O 0
to O 0
totally O 0
abolish O 0
the O 0
deleterious O 0
renal O 0
effects O 0
of O 0
indomethacin B-Chemical 0
, O 0
whereas O 0
the O 0
800 O 0
- O 0
micrograms O 0
dose O 0
resulted O 0
in O 0
significant O 0
worsening O 0
of O 0
renal O 0
hemodynamics O 0
and O 0
sodium B-Chemical 0
retention O 0
. O 0

These O 0
changes O 0
were O 0
maximal O 0
in O 0
the O 0
hour O 0
immediately O 0
after O 0
medications O 0
and O 0
slowly O 0
returned O 0
toward O 0
base O 0
- O 0
line O 0
levels O 0
thereafter O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
the O 0
renal O 0
protective O 0
effects O 0
of O 0
misoprostol B-Chemical 0
is O 0
dose O 0
- O 0
dependent O 0
. O 0

However O 0
, O 0
until O 0
this O 0
apparent O 0
ability O 0
of O 0
200 O 0
micrograms O 0
of O 0
misoprostol B-Chemical 0
to O 0
prevent O 0
the O 0
adverse O 0
effects O 0
of O 0
indomethacin B-Chemical 0
on O 0
renal O 0
function O 0
is O 0
confirmed O 0
with O 0
chronic O 0
frequent O 0
dosing O 0
, O 0
it O 0
would O 0
be O 0
prudent O 0
to O 0
avoid O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
therapy O 0
in O 0
patients O 0
with O 0
cirrhosis B-Disease 0
. O 0

Increased O 0
frequency O 0
and O 0
severity O 0
of O 0
angio B-Disease 0
- I-Disease 0
oedema I-Disease 0
related O 0
to O 0
long O 0
- O 0
term O 0
therapy O 0
with O 0
angiotensin B-Chemical 0
- I-Chemical 0
converting I-Chemical 0
enzyme I-Chemical 0
inhibitor I-Chemical 0
in O 0
two O 0
patients O 0
. O 0

Adverse O 0
reactions O 0
to O 0
drugs O 0
are O 0
well O 0
recognized O 0
as O 0
a O 0
cause O 0
of O 0
acute O 0
or O 0
chronic O 0
urticaria B-Disease 0
, O 0
and O 0
angio B-Disease 0
- I-Disease 0
oedema I-Disease 0
. O 0

Angiotensin B-Chemical 0
- I-Chemical 0
converting I-Chemical 0
enzyme I-Chemical 0
( I-Chemical 0
ACE I-Chemical 0
) I-Chemical 0
inhibitors I-Chemical 0
, O 0
used O 0
to O 0
treat O 0
hypertension B-Disease 0
and O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
, O 0
were O 0
introduced O 0
in O 0
Europe O 0
in O 0
the O 0
middle O 0
of O 0
the O 0
eighties O 0
, O 0
and O 0
the O 0
use O 0
of O 0
these O 0
drugs O 0
has O 0
increased O 0
progressively O 0
. O 0

Soon O 0
after O 0
the O 0
introduction O 0
of O 0
ACE B-Chemical 0
inhibitors I-Chemical 0
, O 0
acute O 0
bouts O 0
of O 0
angio B-Disease 0
- I-Disease 0
oedema I-Disease 0
were O 0
reported O 0
in O 0
association O 0
with O 0
the O 0
use O 0
of O 0
these O 0
drugs O 0
. O 0

We O 0
wish O 0
to O 0
draw O 0
attention O 0
to O 0
the O 0
possibility O 0
of O 0
adverse O 0
reactions O 0
to O 0
ACE B-Chemical 0
inhibitors I-Chemical 0
after O 0
long O 0
- O 0
term O 0
use O 0
and O 0
in O 0
patients O 0
with O 0
pre O 0
- O 0
existing O 0
angio B-Disease 0
- I-Disease 0
oedema I-Disease 0
. O 0

Myoclonus B-Disease 0
associated O 0
with O 0
lorazepam B-Chemical 0
therapy O 0
in O 0
very O 0
- O 0
low O 0
- O 0
birth O 0
- O 0
weight O 0
infants O 0
. O 0

Lorazepam B-Chemical 0
is O 0
being O 0
used O 0
with O 0
increasing O 0
frequency O 0
as O 0
a O 0
sedative O 0
in O 0
the O 0
newborn O 0
and O 0
the O 0
young O 0
infant O 0
. O 0

Concern O 0
has O 0
been O 0
raised O 0
with O 0
regard O 0
to O 0
the O 0
safety O 0
of O 0
lorazepam B-Chemical 0
in O 0
this O 0
age O 0
group O 0
, O 0
especially O 0
in O 0
very O 0
- O 0
low O 0
- O 0
birth O 0
- O 0
weight O 0
( O 0
VLBW O 0
; O 0
< O 0
1 O 0
, O 0
500 O 0
g O 0
) O 0
infants O 0
. O 0

Three O 0
young O 0
infants O 0
, O 0
all O 0
of O 0
birth O 0
weight O 0
< O 0
1 O 0
, O 0
500 O 0
g O 0
, O 0
experienced O 0
myoclonus B-Disease 0
following O 0
the O 0
intravenous O 0
administration O 0
of O 0
lorazepam B-Chemical 0
. O 0

The O 0
potential O 0
neurotoxic B-Disease 0
effects O 0
of O 0
the O 0
drug O 0
( O 0
and O 0
its O 0
vehicle O 0
) O 0
in O 0
this O 0
population O 0
are O 0
discussed O 0
. O 0

Injectable O 0
lorazepam B-Chemical 0
should O 0
be O 0
used O 0
with O 0
caution O 0
in O 0
VLBW O 0
infants O 0
. O 0

Transvenous O 0
right O 0
ventricular O 0
pacing O 0
during O 0
cardiopulmonary O 0
resuscitation O 0
of O 0
pediatric O 0
patients O 0
with O 0
acute O 0
cardiomyopathy B-Disease 0
. O 0

We O 0
describe O 0
the O 0
cardiopulmonary O 0
resuscitation O 0
efforts O 0
on O 0
five O 0
patients O 0
who O 0
presented O 0
in O 0
acute O 0
circulatory B-Disease 0
failure I-Disease 0
from O 0
myocardial B-Disease 0
dysfunction I-Disease 0
. O 0

Three O 0
patients O 0
had O 0
acute O 0
viral O 0
myocarditis B-Disease 0
, O 0
one O 0
had O 0
a O 0
carbamazepine B-Chemical 0
- O 0
induced O 0
acute O 0
eosinophilic B-Disease 0
myocarditis I-Disease 0
, O 0
and O 0
one O 0
had O 0
cardiac O 0
hemosiderosis O 0
resulting O 0
in O 0
acute O 0
cardiogenic B-Disease 0
shock I-Disease 0
. O 0

All O 0
patients O 0
were O 0
continuously O 0
monitored O 0
with O 0
central O 0
venous O 0
and O 0
arterial O 0
catheters O 0
in O 0
addition O 0
to O 0
routine O 0
noninvasive O 0
monitoring O 0
. O 0

An O 0
introducer O 0
sheath O 0
, O 0
a O 0
pacemaker O 0
, O 0
and O 0
sterile O 0
pacing O 0
wires O 0
were O 0
made O 0
readily O 0
available O 0
for O 0
the O 0
patients O 0
, O 0
should O 0
the O 0
need O 0
arise O 0
to O 0
terminate O 0
resistant O 0
cardiac O 0
dysrhythmias B-Disease 0
. O 0

All O 0
patients O 0
developed O 0
cardiocirculatory O 0
arrest O 0
associated O 0
with O 0
extreme O 0
hypotension B-Disease 0
and O 0
dysrhythmias B-Disease 0
within O 0
the O 0
first O 0
48 O 0
hours O 0
of O 0
their O 0
admission O 0
to O 0
the O 0
pediatric O 0
intensive O 0
care O 0
unit O 0
( O 0
PICU O 0
) O 0
. O 0

Right O 0
ventricular O 0
pacemaker O 0
wires O 0
were O 0
inserted O 0
in O 0
all O 0
of O 0
them O 0
during O 0
cardiopulmonary O 0
resuscitation O 0
( O 0
CPR O 0
) O 0
. O 0

In O 0
four O 0
patients O 0
, O 0
cardiac O 0
pacing O 0
was O 0
used O 0
, O 0
resulting O 0
in O 0
a O 0
temporary O 0
captured O 0
rhythm O 0
and O 0
restoration O 0
of O 0
their O 0
cardiac O 0
output O 0
. O 0

These O 0
patients O 0
had O 0
a O 0
second O 0
event O 0
of O 0
cardiac B-Disease 0
arrest I-Disease 0
, O 0
resulting O 0
in O 0
death O 0
, O 0
within O 0
10 O 0
to O 0
60 O 0
minutes O 0
. O 0

In O 0
one O 0
patient O 0
, O 0
cardiac O 0
pacing O 0
was O 0
not O 0
used O 0
, O 0
because O 0
he O 0
converted O 0
to O 0
normal O 0
sinus O 0
rhythm O 0
by O 0
electrical O 0
defibrillation O 0
within O 0
three O 0
minutes O 0
of O 0
initiating O 0
CPR O 0
. O 0

We O 0
conclude O 0
that O 0
cardiac O 0
pacing O 0
during O 0
resuscitative O 0
efforts O 0
in O 0
pediatric O 0
patients O 0
suffering O 0
from O 0
acute O 0
myocardial B-Disease 0
dysfunction I-Disease 0
may O 0
not O 0
have O 0
long O 0
- O 0
term O 0
value O 0
in O 0
and O 0
of O 0
itself O 0
; O 0
however O 0
, O 0
if O 0
temporary O 0
hemodynamic O 0
stability O 0
is O 0
achieved O 0
by O 0
this O 0
procedure O 0
, O 0
it O 0
may O 0
provide O 0
additional O 0
time O 0
needed O 0
to O 0
institute O 0
other O 0
therapeutic O 0
modalities O 0
. O 0

Efficacy O 0
and O 0
safety O 0
of O 0
granisetron B-Chemical 0
, O 0
a O 0
selective O 0
5 B-Chemical 0
- I-Chemical 0
hydroxytryptamine I-Chemical 0
- O 0
3 O 0
receptor O 0
antagonist O 0
, O 0
in O 0
the O 0
prevention O 0
of O 0
nausea B-Disease 0
and O 0
vomiting B-Disease 0
induced O 0
by O 0
high O 0
- O 0
dose O 0
cisplatin B-Chemical 0
. O 0

PURPOSE O 0
: O 0
To O 0
assess O 0
the O 0
antiemetic O 0
effects O 0
and O 0
safety O 0
profile O 0
of O 0
four O 0
different O 0
doses O 0
of O 0
granisetron B-Chemical 0
( O 0
Kytril B-Chemical 0
; O 0
SmithKline O 0
Beecham O 0
Pharmaceuticals O 0
, O 0
Philadelphia O 0
, O 0
PA O 0
) O 0
when O 0
administered O 0
as O 0
a O 0
single O 0
intravenous O 0
( O 0
IV O 0
) O 0
dose O 0
for O 0
prophylaxis O 0
of O 0
cisplatin B-Chemical 0
- O 0
induced O 0
nausea B-Disease 0
and O 0
vomiting B-Disease 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
One O 0
hundred O 0
eighty O 0
- O 0
four O 0
chemotherapy O 0
- O 0
naive O 0
patients O 0
receiving O 0
high O 0
- O 0
dose O 0
cisplatin B-Chemical 0
( O 0
81 O 0
to O 0
120 O 0
mg O 0
/ O 0
m2 O 0
) O 0
were O 0
randomized O 0
to O 0
receive O 0
one O 0
of O 0
four O 0
granisetron B-Chemical 0
doses O 0
( O 0
5 O 0
, O 0
10 O 0
, O 0
20 O 0
, O 0
or O 0
40 O 0
micrograms O 0
/ O 0
kg O 0
) O 0
administered O 0
before O 0
chemotherapy O 0
. O 0

Patients O 0
were O 0
observed O 0
on O 0
an O 0
inpatient O 0
basis O 0
for O 0
18 O 0
to O 0
24 O 0
hours O 0
, O 0
and O 0
vital O 0
signs O 0
, O 0
nausea B-Disease 0
, O 0
vomiting B-Disease 0
, O 0
retching O 0
, O 0
and O 0
appetite O 0
were O 0
assessed O 0
. O 0

Safety O 0
analyses O 0
included O 0
incidence O 0
of O 0
adverse O 0
experiences O 0
and O 0
laboratory O 0
parameter O 0
changes O 0
. O 0

RESULTS O 0
: O 0
After O 0
granisetron B-Chemical 0
doses O 0
of O 0
5 O 0
, O 0
10 O 0
, O 0
20 O 0
, O 0
and O 0
40 O 0
micrograms O 0
/ O 0
kg O 0
, O 0
a O 0
major O 0
response O 0
( O 0
< O 0
or O 0
= O 0
two O 0
vomiting B-Disease 0
or O 0
retching O 0
episodes O 0
, O 0
and O 0
no O 0
antiemetic O 0
rescue O 0
) O 0
was O 0
recorded O 0
in O 0
23 O 0
% O 0
, O 0
57 O 0
% O 0
, O 0
58 O 0
% O 0
, O 0
and O 0
60 O 0
% O 0
of O 0
patients O 0
, O 0
respectively O 0
, O 0
and O 0
a O 0
complete O 0
response O 0
( O 0
no O 0
vomiting B-Disease 0
or O 0
retching O 0
, O 0
and O 0
no O 0
antiemetic O 0
rescue O 0
) O 0
in O 0
18 O 0
% O 0
, O 0
41 O 0
% O 0
, O 0
40 O 0
% O 0
, O 0
and O 0
47 O 0
% O 0
of O 0
patients O 0
, O 0
respectively O 0
. O 0

There O 0
was O 0
a O 0
statistically O 0
longer O 0
time O 0
to O 0
first O 0
episode O 0
of O 0
nausea B-Disease 0
( O 0
P O 0
= O 0
. O 0
0015 O 0
) O 0
and O 0
vomiting B-Disease 0
( O 0
P O 0
= O 0
. O 0
0001 O 0
) O 0
, O 0
and O 0
fewer O 0
patients O 0
were O 0
administered O 0
additional O 0
antiemetic O 0
medication O 0
in O 0
the O 0
10 O 0
- O 0
micrograms O 0
/ O 0
kg O 0
dosing O 0
groups O 0
than O 0
in O 0
the O 0
5 O 0
- O 0
micrograms O 0
/ O 0
kg O 0
dosing O 0
group O 0
. O 0

As O 0
granisetron B-Chemical 0
dose O 0
increased O 0
, O 0
appetite O 0
return O 0
increased O 0
( O 0
P O 0
= O 0
. O 0
040 O 0
) O 0
. O 0

Headache B-Disease 0
was O 0
the O 0
most O 0
frequently O 0
reported O 0
adverse O 0
event O 0
( O 0
20 O 0
% O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
A O 0
single O 0
10 O 0
- O 0
, O 0
20 O 0
- O 0
, O 0
or O 0
40 O 0
- O 0
micrograms O 0
/ O 0
kg O 0
dose O 0
of O 0
granisetron B-Chemical 0
was O 0
effective O 0
in O 0
controlling O 0
vomiting B-Disease 0
in O 0
57 O 0
% O 0
to O 0
60 O 0
% O 0
of O 0
patients O 0
who O 0
received O 0
cisplatin B-Chemical 0
at O 0
doses O 0
greater O 0
than O 0
81 O 0
mg O 0
/ O 0
m2 O 0
and O 0
totally O 0
prevented O 0
vomiting B-Disease 0
in O 0
40 O 0
% O 0
to O 0
47 O 0
% O 0
of O 0
patients O 0
. O 0

There O 0
were O 0
no O 0
statistically O 0
significant O 0
differences O 0
in O 0
efficacy O 0
between O 0
the O 0
10 O 0
- O 0
micrograms O 0
/ O 0
kg O 0
dose O 0
and O 0
the O 0
20 O 0
- O 0
and O 0
40 O 0
- O 0
micrograms O 0
/ O 0
kg O 0
doses O 0
. O 0

Granisetron B-Chemical 0
was O 0
well O 0
tolerated O 0
at O 0
all O 0
doses O 0
. O 0

Adverse O 0
interaction O 0
between O 0
clonidine B-Chemical 0
and O 0
verapamil B-Chemical 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
report O 0
two O 0
cases O 0
of O 0
a O 0
possible O 0
adverse O 0
interaction O 0
between O 0
clonidine B-Chemical 0
and O 0
verapamil B-Chemical 0
resulting O 0
in O 0
atrioventricular B-Disease 0
( I-Disease 0
AV I-Disease 0
) I-Disease 0
block I-Disease 0
in O 0
both O 0
patients O 0
and O 0
severe O 0
hypotension B-Disease 0
in O 0
one O 0
patient O 0
. O 0

CASE O 0
SUMMARIES O 0
: O 0
A O 0
54 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
hyperaldosteronism B-Disease 0
was O 0
treated O 0
with O 0
verapamil B-Chemical 0
480 O 0
mg O 0
/ O 0
d O 0
and O 0
spironolactone B-Chemical 0
100 O 0
mg O 0
/ O 0
d O 0
. O 0

After O 0
the O 0
addition O 0
of O 0
a O 0
minimal O 0
dose O 0
of O 0
clonidine B-Chemical 0
( O 0
0 O 0
. O 0
15 O 0
mg O 0
bid O 0
) O 0
, O 0
she O 0
developed O 0
complete O 0
AV B-Disease 0
block I-Disease 0
and O 0
severe O 0
hypotension B-Disease 0
, O 0
which O 0
resolved O 0
upon O 0
cessation O 0
of O 0
all O 0
medications O 0
. O 0

A O 0
65 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
was O 0
treated O 0
with O 0
extended O 0
- O 0
release O 0
verapamil B-Chemical 0
240 O 0
mg O 0
/ O 0
d O 0
. O 0

After O 0
the O 0
addition O 0
of O 0
clonidine B-Chemical 0
0 O 0
. O 0
15 O 0
mg O 0
bid O 0
she O 0
developed O 0
complete O 0
AV B-Disease 0
block I-Disease 0
, O 0
which O 0
resolved O 0
after O 0
all O 0
therapy O 0
was O 0
stopped O 0
. O 0

DISCUSSION O 0
: O 0
An O 0
adverse O 0
interaction O 0
between O 0
clonidine B-Chemical 0
and O 0
verapamil B-Chemical 0
has O 0
not O 0
been O 0
reported O 0
previously O 0
. O 0

We O 0
describe O 0
two O 0
such O 0
cases O 0
and O 0
discuss O 0
the O 0
various O 0
mechanisms O 0
that O 0
might O 0
cause O 0
such O 0
an O 0
interaction O 0
. O 0

Clinicians O 0
should O 0
be O 0
acquainted O 0
with O 0
this O 0
possibly O 0
fatal O 0
interaction O 0
between O 0
two O 0
commonly O 0
used O 0
antihypertensive O 0
drugs O 0
. O 0

CONCLUSIONS O 0
: O 0
Caution O 0
is O 0
recommended O 0
in O 0
combining O 0
clonidine B-Chemical 0
and O 0
verapamil B-Chemical 0
therapy O 0
, O 0
even O 0
in O 0
patients O 0
who O 0
do O 0
not O 0
have O 0
sinus O 0
or O 0
AV O 0
node O 0
dysfunction O 0
. O 0

The O 0
two O 0
drugs O 0
may O 0
act O 0
synergistically O 0
on O 0
both O 0
the O 0
AV O 0
node O 0
and O 0
the O 0
peripheral O 0
circulation O 0
. O 0

Pharmacological O 0
studies O 0
on O 0
a O 0
new O 0
dihydrothienopyridine B-Chemical 0
calcium I-Chemical 0
antagonist O 0
, O 0
S B-Chemical 0
- I-Chemical 0
312 I-Chemical 0
- I-Chemical 0
d I-Chemical 0
. O 0

5th O 0
communication O 0
: O 0
anticonvulsant O 0
effects O 0
in O 0
mice O 0
. O 0

S B-Chemical 0
- I-Chemical 0
312 I-Chemical 0
, O 0
S B-Chemical 0
- I-Chemical 0
312 I-Chemical 0
- I-Chemical 0
d I-Chemical 0
, O 0
but O 0
not O 0
S B-Chemical 0
- I-Chemical 0
312 I-Chemical 0
- I-Chemical 0
l I-Chemical 0
, O 0
L O 0
- O 0
type O 0
calcium B-Chemical 0
channel O 0
antagonists O 0
, O 0
showed O 0
anticonvulsant O 0
effects O 0
on O 0
the O 0
audiogenic B-Disease 0
tonic I-Disease 0
convulsions I-Disease 0
in O 0
DBA O 0
/ O 0
2 O 0
mice O 0
; O 0
and O 0
their O 0
ED50 O 0
values O 0
were O 0
18 O 0
. O 0
4 O 0
( O 0
12 O 0
. O 0
8 O 0
- O 0
27 O 0
. O 0
1 O 0
) O 0
mg O 0
/ O 0
kg O 0
, O 0
p O 0
. O 0
o O 0
. O 0
and O 0
15 O 0
. O 0
0 O 0
( O 0
10 O 0
. O 0
2 O 0
- O 0
23 O 0
. O 0
7 O 0
) O 0
mg O 0
/ O 0
kg O 0
, O 0
p O 0
. O 0
o O 0
. O 0
, O 0
respectively O 0
, O 0
while O 0
that O 0
of O 0
flunarizine B-Chemical 0
was O 0
34 O 0
. O 0
0 O 0
( O 0
26 O 0
. O 0
0 O 0
- O 0
44 O 0
. O 0
8 O 0
) O 0
mg O 0
/ O 0
kg O 0
, O 0
p O 0
. O 0
o O 0
. O 0

Although O 0
moderate O 0
anticonvulsant O 0
effects O 0
of O 0
S B-Chemical 0
- I-Chemical 0
312 I-Chemical 0
- I-Chemical 0
d I-Chemical 0
in O 0
higher O 0
doses O 0
were O 0
observed O 0
against O 0
the O 0
clonic O 0
convulsions B-Disease 0
induced O 0
by O 0
pentylenetetrazole B-Chemical 0
( O 0
85 O 0
mg O 0
/ O 0
kg O 0
, O 0
s O 0
. O 0
c O 0
. O 0
) O 0
or O 0
bemegride B-Chemical 0
( O 0
40 O 0
mg O 0
/ O 0
kg O 0
, O 0
s O 0
. O 0
c O 0
. O 0
) O 0
, O 0
no O 0
effects O 0
were O 0
observed O 0
in O 0
convulsions B-Disease 0
induced O 0
by O 0
N B-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
- I-Chemical 0
D I-Chemical 0
- I-Chemical 0
aspartate I-Chemical 0
, O 0
picrotoxin B-Chemical 0
, O 0
or O 0
electroshock O 0
in O 0
Slc O 0
: O 0
ddY O 0
mice O 0
. O 0

S B-Chemical 0
- I-Chemical 0
312 I-Chemical 0
- I-Chemical 0
d I-Chemical 0
may O 0
be O 0
useful O 0
in O 0
the O 0
therapy O 0
of O 0
certain O 0
types O 0
of O 0
human O 0
epilepsy B-Disease 0
. O 0

Transmural O 0
myocardial B-Disease 0
infarction I-Disease 0
with O 0
sumatriptan B-Chemical 0
. O 0

For O 0
sumatriptan B-Chemical 0
, O 0
tightness O 0
in O 0
the O 0
chest O 0
caused O 0
by O 0
an O 0
unknown O 0
mechanism O 0
has O 0
been O 0
reported O 0
in O 0
3 O 0
- O 0
5 O 0
% O 0
of O 0
users O 0
. O 0

We O 0
describe O 0
a O 0
47 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
an O 0
acute O 0
myocardial B-Disease 0
infarction I-Disease 0
after O 0
administration O 0
of O 0
sumatriptan B-Chemical 0
6 O 0
mg O 0
subcutaneously O 0
for O 0
cluster B-Disease 0
headache I-Disease 0
. O 0

The O 0
patient O 0
had O 0
no O 0
history O 0
of O 0
underlying O 0
ischaemic B-Disease 0
heart I-Disease 0
disease I-Disease 0
or O 0
Prinzmetal B-Disease 0
' I-Disease 0
s I-Disease 0
angina I-Disease 0
. O 0

She O 0
recovered O 0
without O 0
complications O 0
. O 0

Flumazenil B-Chemical 0
induces O 0
seizures B-Disease 0
and O 0
death O 0
in O 0
mixed O 0
cocaine B-Chemical 0
- O 0
diazepam B-Chemical 0
intoxications O 0
. O 0

STUDY O 0
HYPOTHESIS O 0
: O 0
Administration O 0
of O 0
the O 0
benzodiazepine B-Chemical 0
antagonist O 0
flumazenil B-Chemical 0
may O 0
unmask O 0
seizures B-Disease 0
in O 0
mixed O 0
cocaine B-Chemical 0
- O 0
benzodiazepine B-Chemical 0
intoxication O 0
. O 0

DESIGN O 0
: O 0
Male O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
received O 0
100 O 0
mg O 0
/ O 0
kg O 0
cocaine B-Chemical 0
IP O 0
alone O 0
, O 0
5 O 0
mg O 0
/ O 0
kg O 0
diazepam B-Chemical 0
alone O 0
, O 0
or O 0
a O 0
combination O 0
of O 0
diazepam B-Chemical 0
and O 0
cocaine B-Chemical 0
. O 0

Three O 0
minutes O 0
later O 0
, O 0
groups O 0
were O 0
challenged O 0
with O 0
vehicle O 0
or O 0
flumazenil B-Chemical 0
5 O 0
or O 0
10 O 0
mg O 0
/ O 0
kg O 0
IP O 0
. O 0

Animal O 0
behavior O 0
, O 0
seizures B-Disease 0
( O 0
time O 0
to O 0
and O 0
incidence O 0
) O 0
, O 0
death O 0
( O 0
time O 0
to O 0
and O 0
incidence O 0
) O 0
, O 0
and O 0
cortical O 0
EEG O 0
tracings O 0
were O 0
recorded O 0
. O 0

INTERVENTIONS O 0
: O 0
Administration O 0
of O 0
flumazenil B-Chemical 0
to O 0
animals O 0
after O 0
they O 0
had O 0
received O 0
a O 0
combination O 0
dose O 0
of O 0
cocaine B-Chemical 0
and O 0
diazepam B-Chemical 0
. O 0

RESULTS O 0
: O 0
In O 0
group O 0
1 O 0
, O 0
animals O 0
received O 0
cocaine B-Chemical 0
followed O 0
by O 0
vehicle O 0
. O 0

This O 0
resulted O 0
in O 0
100 O 0
% O 0
developing O 0
seizures B-Disease 0
and O 0
death O 0
. O 0

Group O 0
2 O 0
received O 0
diazepam B-Chemical 0
alone O 0
followed O 0
by O 0
vehicle O 0
. O 0

Animals O 0
became O 0
somnolent O 0
and O 0
none O 0
died O 0
. O 0

Group O 0
3 O 0
received O 0
diazepam B-Chemical 0
followed O 0
by O 0
5 O 0
mg O 0
/ O 0
kg O 0
flumazenil B-Chemical 0
. O 0

Animals O 0
became O 0
somnolent O 0
after O 0
diazepam B-Chemical 0
and O 0
then O 0
active O 0
after O 0
flumazenil B-Chemical 0
administration O 0
. O 0

In O 0
group O 0
4 O 0
, O 0
a O 0
combination O 0
of O 0
cocaine B-Chemical 0
and O 0
diazepam B-Chemical 0
was O 0
administered O 0
simultaneously O 0
. O 0

This O 0
resulted O 0
in O 0
no O 0
overt O 0
or O 0
EEG O 0
- O 0
detectable O 0
seizures B-Disease 0
and O 0
a O 0
50 O 0
% O 0
incidence O 0
of O 0
death O 0
. O 0

Group O 0
5 O 0
received O 0
a O 0
similar O 0
combination O 0
of O 0
cocaine B-Chemical 0
and O 0
diazepam B-Chemical 0
, O 0
followed O 0
later O 0
by O 0
5 O 0
mg O 0
/ O 0
kg O 0
flumazenil B-Chemical 0
. O 0

This O 0
resulted O 0
in O 0
an O 0
increased O 0
incidence O 0
of O 0
seizures B-Disease 0
, O 0
90 O 0
% O 0
( O 0
P O 0
< O 0
. O 0
01 O 0
) O 0
, O 0
and O 0
death O 0
, O 0
100 O 0
% O 0
( O 0
P O 0
< O 0
or O 0
= O 0
. O 0
01 O 0
) O 0
, O 0
compared O 0
with O 0
group O 0
4 O 0
. O 0

Group O 0
6 O 0
received O 0
cocaine B-Chemical 0
and O 0
diazepam B-Chemical 0
followed O 0
by O 0
10 O 0
mg O 0
/ O 0
kg O 0
flumazenil B-Chemical 0
. O 0

This O 0
also O 0
resulted O 0
in O 0
an O 0
increased O 0
incidence O 0
of O 0
seizures B-Disease 0
, O 0
90 O 0
% O 0
( O 0
P O 0
< O 0
or O 0
= O 0
. O 0
01 O 0
) O 0
, O 0
and O 0
death O 0
, O 0
90 O 0
% O 0
( O 0
P O 0
< O 0
or O 0
= O 0
. O 0
05 O 0
) O 0
, O 0
compared O 0
with O 0
group O 0
4 O 0
. O 0

CONCLUSION O 0
: O 0
Flumazenil B-Chemical 0
can O 0
unmask O 0
seizures B-Disease 0
and O 0
increase O 0
the O 0
incidence O 0
of O 0
death O 0
in O 0
a O 0
model O 0
of O 0
combined O 0
cocaine B-Chemical 0
- O 0
diazepam B-Chemical 0
intoxications O 0
. O 0

Mechanisms O 0
for O 0
protective O 0
effects O 0
of O 0
free O 0
radical O 0
scavengers O 0
on O 0
gentamicin B-Chemical 0
- O 0
mediated O 0
nephropathy B-Disease 0
in O 0
rats O 0
. O 0

Studies O 0
were O 0
performed O 0
to O 0
examine O 0
the O 0
mechanisms O 0
for O 0
the O 0
protective O 0
effects O 0
of O 0
free O 0
radical O 0
scavengers O 0
on O 0
gentamicin B-Chemical 0
( O 0
GM B-Chemical 0
) O 0
- O 0
mediated O 0
nephropathy B-Disease 0
. O 0

Administration O 0
of O 0
GM B-Chemical 0
at O 0
40 O 0
mg O 0
/ O 0
kg O 0
sc O 0
for O 0
13 O 0
days O 0
to O 0
rats O 0
induced O 0
a O 0
significant O 0
reduction O 0
in O 0
renal O 0
blood O 0
flow O 0
( O 0
RBF O 0
) O 0
and O 0
inulin O 0
clearance O 0
( O 0
CIn O 0
) O 0
as O 0
well O 0
as O 0
marked O 0
tubular B-Disease 0
damage I-Disease 0
. O 0

A O 0
significant O 0
reduction O 0
in O 0
urinary O 0
guanosine B-Chemical 0
3 I-Chemical 0
' I-Chemical 0
, I-Chemical 0
5 I-Chemical 0
' I-Chemical 0
- I-Chemical 0
cyclic I-Chemical 0
monophosphate I-Chemical 0
( O 0
cGMP B-Chemical 0
) O 0
excretion O 0
and O 0
a O 0
significant O 0
increase O 0
in O 0
renal O 0
cortical O 0
renin O 0
and O 0
endothelin O 0
- O 0
1 O 0
contents O 0
were O 0
also O 0
observed O 0
in O 0
GM B-Chemical 0
- O 0
mediated O 0
nephropathy B-Disease 0
. O 0

Superoxide B-Chemical 0
dismutase O 0
( O 0
SOD O 0
) O 0
or O 0
dimethylthiourea B-Chemical 0
( O 0
DMTU B-Chemical 0
) O 0
significantly O 0
lessened O 0
the O 0
GM B-Chemical 0
- O 0
induced O 0
decrement O 0
in O 0
CIn O 0
. O 0

The O 0
SOD O 0
- O 0
induced O 0
increase O 0
in O 0
glomerular O 0
filtration O 0
rate O 0
was O 0
associated O 0
with O 0
a O 0
marked O 0
improvement O 0
in O 0
RBF O 0
, O 0
an O 0
increase O 0
in O 0
urinary O 0
cGMP B-Chemical 0
excretion O 0
, O 0
and O 0
a O 0
decrease O 0
in O 0
renal O 0
renin O 0
and O 0
endothelin O 0
- O 0
1 O 0
content O 0
. O 0

SOD O 0
did O 0
not O 0
attenuate O 0
the O 0
tubular B-Disease 0
damage I-Disease 0
. O 0

In O 0
contrast O 0
, O 0
DMTU B-Chemical 0
significantly O 0
reduced O 0
the O 0
tubular B-Disease 0
damage I-Disease 0
and O 0
lipid O 0
peroxidation O 0
, O 0
but O 0
it O 0
did O 0
not O 0
affect O 0
renal O 0
hemodynamics O 0
and O 0
vasoactive O 0
substances O 0
. O 0

Neither O 0
SOD O 0
nor O 0
DMTU B-Chemical 0
affected O 0
the O 0
renal O 0
cortical O 0
GM B-Chemical 0
content O 0
in O 0
GM B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
1 O 0
) O 0
both O 0
SOD O 0
and O 0
DMTU B-Chemical 0
have O 0
protective O 0
effects O 0
on O 0
GM B-Chemical 0
- O 0
mediated O 0
nephropathy B-Disease 0
, O 0
2 O 0
) O 0
the O 0
mechanisms O 0
for O 0
the O 0
protective O 0
effects O 0
differ O 0
for O 0
SOD O 0
and O 0
DMTU B-Chemical 0
, O 0
and O 0
3 O 0
) O 0
superoxide B-Chemical 0
anions O 0
play O 0
a O 0
critical O 0
role O 0
in O 0
GM B-Chemical 0
- O 0
induced O 0
renal O 0
vasoconstriction O 0
. O 0

Cephalothin B-Chemical 0
- O 0
induced O 0
immune O 0
hemolytic B-Disease 0
anemia I-Disease 0
. O 0

A O 0
patient O 0
with O 0
renal B-Disease 0
disease I-Disease 0
developed O 0
Coombs O 0
- O 0
positive O 0
hemolytic B-Disease 0
anemia I-Disease 0
while O 0
receiving O 0
cephalothin B-Chemical 0
therapy O 0
. O 0

An O 0
anti O 0
- O 0
cephalothin B-Chemical 0
IgG O 0
antibody O 0
was O 0
detected O 0
in O 0
the O 0
patient O 0
' O 0
s O 0
serum O 0
and O 0
in O 0
the O 0
eluates O 0
from O 0
her O 0
erythrocytes O 0
. O 0

In O 0
addition O 0
, O 0
nonimmunologic O 0
binding O 0
of O 0
normal O 0
and O 0
patient O 0
' O 0
s O 0
serum O 0
proteins O 0
to O 0
her O 0
own O 0
and O 0
cephalothin B-Chemical 0
- O 0
coated O 0
normal O 0
red O 0
cells O 0
was O 0
demonstrated O 0
. O 0

Skin O 0
tests O 0
and O 0
in O 0
vitro O 0
lymphocyte O 0
stimulation O 0
revealed O 0
that O 0
the O 0
patient O 0
was O 0
sensitized O 0
to O 0
cephalothin B-Chemical 0
and O 0
also O 0
to O 0
ampicillin B-Chemical 0
. O 0

Careful O 0
investigation O 0
of O 0
drug O 0
- O 0
induced O 0
hemolytic B-Disease 0
anemias I-Disease 0
reveals O 0
the O 0
complexity O 0
of O 0
the O 0
immune O 0
mechanisms O 0
involved O 0
. O 0

Assessment O 0
of O 0
cardiomyocyte O 0
DNA O 0
synthesis O 0
during O 0
hypertrophy B-Disease 0
in O 0
adult O 0
mice O 0
. O 0

The O 0
ability O 0
of O 0
cardiomyocytes O 0
to O 0
synthesize O 0
DNA O 0
in O 0
response O 0
to O 0
experimentally O 0
induced O 0
cardiac B-Disease 0
hypertrophy I-Disease 0
was O 0
assessed O 0
in O 0
adult O 0
mice O 0
. O 0

Isoproterenol B-Chemical 0
delivered O 0
by O 0
osmotic O 0
minipump O 0
implantation O 0
in O 0
adult O 0
C3Heb O 0
/ O 0
FeJ O 0
mice O 0
resulted O 0
in O 0
a O 0
46 O 0
% O 0
increase O 0
in O 0
heart O 0
weight O 0
and O 0
a O 0
19 O 0
. O 0
3 O 0
% O 0
increase O 0
in O 0
cardiomyocyte O 0
area O 0
. O 0

No O 0
DNA O 0
synthesis O 0
, O 0
as O 0
assessed O 0
by O 0
autoradiographic O 0
analysis O 0
of O 0
isolated O 0
cardiomyocytes O 0
, O 0
was O 0
observed O 0
in O 0
control O 0
or O 0
hypertrophic B-Disease 0
hearts I-Disease 0
. O 0

A O 0
survey O 0
of O 0
15 O 0
independent O 0
inbred O 0
strains O 0
of O 0
mice O 0
revealed O 0
that O 0
ventricular O 0
cardiomyocyte O 0
nuclear O 0
number O 0
ranged O 0
from O 0
3 O 0
to O 0
13 O 0
% O 0
mononucleate O 0
, O 0
suggesting O 0
that O 0
cardiomyocyte O 0
terminal O 0
differentiation O 0
is O 0
influenced O 0
directly O 0
or O 0
indirectly O 0
by O 0
genetic O 0
background O 0
. O 0

To O 0
determine O 0
whether O 0
the O 0
capacity O 0
for O 0
reactive O 0
DNA O 0
synthesis O 0
was O 0
also O 0
subject O 0
to O 0
genetic O 0
regulation O 0
, O 0
cardiac B-Disease 0
hypertrophy I-Disease 0
was O 0
induced O 0
in O 0
the O 0
strains O 0
of O 0
mice O 0
comprising O 0
the O 0
extremes O 0
of O 0
the O 0
nuclear O 0
number O 0
survey O 0
. O 0

These O 0
data O 0
indicate O 0
that O 0
adult O 0
mouse O 0
atrial O 0
and O 0
ventricular O 0
cardiomyocytes O 0
do O 0
not O 0
synthesize O 0
DNA O 0
in O 0
response O 0
to O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
hypertrophy I-Disease 0
. O 0

Central O 0
cardiovascular O 0
effects O 0
of O 0
AVP B-Chemical 0
and O 0
ANP O 0
in O 0
normotensive O 0
and O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
. O 0

The O 0
purpose O 0
of O 0
the O 0
present O 0
study O 0
was O 0
to O 0
compare O 0
influence O 0
of O 0
central O 0
arginine B-Chemical 0
vasopressin I-Chemical 0
( O 0
AVP B-Chemical 0
) O 0
and O 0
of O 0
atrial O 0
natriuretic O 0
peptide O 0
( O 0
ANP O 0
) O 0
on O 0
control O 0
of O 0
arterial O 0
blood O 0
pressure O 0
( O 0
MAP O 0
) O 0
and O 0
heart O 0
rate O 0
( O 0
HR O 0
) O 0
in O 0
normotensive O 0
( O 0
WKY O 0
) O 0
and O 0
spontaneously O 0
hypertensive B-Disease 0
( O 0
SHR O 0
) O 0
rats O 0
. O 0

Three O 0
series O 0
of O 0
experiments O 0
were O 0
performed O 0
on O 0
30 O 0
WKY O 0
and O 0
30 O 0
SHR O 0
, O 0
chronically O 0
instrumented O 0
with O 0
guide O 0
tubes O 0
in O 0
the O 0
lateral O 0
ventricle O 0
( O 0
LV O 0
) O 0
and O 0
arterial O 0
and O 0
venous O 0
catheters O 0
. O 0

MAP O 0
and O 0
HR O 0
were O 0
monitored O 0
before O 0
and O 0
after O 0
i O 0
. O 0
v O 0
. O 0
injections O 0
of O 0
either O 0
vehicle O 0
or O 0
1 O 0
, O 0
10 O 0
and O 0
50 O 0
ng O 0
of O 0
AVP B-Chemical 0
and O 0
25 O 0
, O 0
125 O 0
and O 0
500 O 0
ng O 0
of O 0
ANP O 0
. O 0

Sensitivity O 0
of O 0
cardiac O 0
component O 0
of O 0
baroreflex O 0
( O 0
CCB O 0
) O 0
, O 0
expressed O 0
as O 0
a O 0
slope O 0
of O 0
the O 0
regression O 0
line O 0
was O 0
determined O 0
from O 0
relationships O 0
between O 0
systolic O 0
arterial O 0
pressure O 0
( O 0
SAP O 0
) O 0
and O 0
HR O 0
period O 0
( O 0
HRp O 0
) O 0
during O 0
phenylephrine B-Chemical 0
( O 0
Phe B-Chemical 0
) O 0
- O 0
induced O 0
hypertension B-Disease 0
and O 0
sodium B-Chemical 0
nitroprusside I-Chemical 0
( O 0
SN B-Chemical 0
) O 0
- O 0
induced O 0
hypotension B-Disease 0
. O 0

CCB O 0
was O 0
measured O 0
before O 0
and O 0
after O 0
administration O 0
of O 0
either O 0
vehicle O 0
, O 0
AVP B-Chemical 0
, O 0
ANP O 0
, O 0
or O 0
both O 0
peptides O 0
together O 0
. O 0

Increases O 0
of O 0
MAP O 0
occurred O 0
after O 0
LV O 0
administration O 0
of O 0
1 O 0
, O 0
10 O 0
and O 0
50 O 0
ng O 0
of O 0
AVP B-Chemical 0
in O 0
WKY O 0
and O 0
of O 0
10 O 0
and O 0
50 O 0
ng O 0
in O 0
SHR O 0
. O 0

ANP O 0
did O 0
not O 0
cause O 0
significant O 0
changes O 0
in O 0
MAP O 0
in O 0
both O 0
strains O 0
as O 0
compared O 0
to O 0
vehicle O 0
, O 0
but O 0
it O 0
abolished O 0
AVP B-Chemical 0
- O 0
induced O 0
MAP O 0
increase O 0
in O 0
WKY O 0
and O 0
SHR O 0
. O 0

CCB O 0
was O 0
reduced O 0
in O 0
WKY O 0
and O 0
SHR O 0
after O 0
LV O 0
administration O 0
of O 0
AVP B-Chemical 0
during O 0
SN B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
. O 0

In O 0
SHR O 0
but O 0
not O 0
in O 0
WKY O 0
administration O 0
of O 0
ANP O 0
, O 0
AVP B-Chemical 0
and O 0
ANP O 0
+ O 0
AVP B-Chemical 0
decreased O 0
CCB O 0
during O 0
Phe B-Chemical 0
- O 0
induced O 0
MAP O 0
elevation O 0
. O 0

The O 0
results O 0
indicate O 0
that O 0
centrally O 0
applied O 0
AVP B-Chemical 0
and O 0
ANP O 0
exert O 0
differential O 0
effects O 0
on O 0
blood O 0
pressure O 0
and O 0
baroreflex O 0
control O 0
of O 0
heart O 0
rate O 0
in O 0
WKY O 0
and O 0
SHR O 0
and O 0
suggest O 0
interaction O 0
of O 0
these O 0
two O 0
peptides O 0
in O 0
blood O 0
pressure O 0
regulation O 0
at O 0
the O 0
level O 0
of O 0
central O 0
nervous O 0
system O 0
. O 0

Cutaneous O 0
exposure O 0
to O 0
warfarin B-Chemical 0
- O 0
like O 0
anticoagulant O 0
causing O 0
an O 0
intracerebral B-Disease 0
hemorrhage I-Disease 0
: O 0
a O 0
case O 0
report O 0
. O 0

A O 0
case O 0
of O 0
intercerebral O 0
hematoma B-Disease 0
due O 0
to O 0
warfarin B-Chemical 0
- O 0
induced O 0
coagulopathy B-Disease 0
is O 0
presented O 0
. O 0

The O 0
39 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
had O 0
spread O 0
a O 0
warfarin B-Chemical 0
- O 0
type O 0
rat O 0
poison O 0
around O 0
her O 0
house O 0
weekly O 0
using O 0
her O 0
bare O 0
hands O 0
, O 0
with O 0
no O 0
washing O 0
post O 0
application O 0
. O 0

Percutaneous O 0
absorption O 0
of O 0
warfarin B-Chemical 0
causing O 0
coagulopathy B-Disease 0
, O 0
reported O 0
three O 0
times O 0
in O 0
the O 0
past O 0
, O 0
is O 0
a O 0
significant O 0
risk O 0
if O 0
protective O 0
measures O 0
, O 0
such O 0
as O 0
gloves O 0
, O 0
are O 0
not O 0
used O 0
. O 0

An O 0
adverse O 0
drug O 0
interaction O 0
with O 0
piroxicam B-Chemical 0
, O 0
which O 0
she O 0
took O 0
occasionally O 0
, O 0
may O 0
have O 0
exacerbated O 0
the O 0
coagulopathy B-Disease 0
. O 0

Pediatric O 0
heart O 0
transplantation O 0
without O 0
chronic O 0
maintenance O 0
steroids B-Chemical 0
. O 0

From O 0
1986 O 0
to O 0
February O 0
1993 O 0
, O 0
40 O 0
children O 0
aged O 0
2 O 0
months O 0
to O 0
18 O 0
years O 0
( O 0
average O 0
age O 0
10 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
5 O 0
. O 0
8 O 0
years O 0
) O 0
underwent O 0
heart O 0
transplantation O 0
. O 0

Indications O 0
for O 0
transplantation O 0
were O 0
idiopathic B-Disease 0
cardiomyopathy I-Disease 0
( O 0
52 O 0
% O 0
) O 0
, O 0
congenital B-Disease 0
heart I-Disease 0
disease I-Disease 0
( O 0
35 O 0
% O 0
) O 0
with O 0
and O 0
without O 0
prior O 0
repair O 0
( O 0
71 O 0
% O 0
and O 0
29 O 0
% O 0
, O 0
respectively O 0
) O 0
, O 0
hypertrophic B-Disease 0
cardiomyopathy I-Disease 0
( O 0
5 O 0
% O 0
) O 0
, O 0
valvular B-Disease 0
heart I-Disease 0
disease I-Disease 0
( O 0
3 O 0
% O 0
) O 0
, O 0
and O 0
doxorubicin B-Chemical 0
cardiomyopathy B-Disease 0
( O 0
5 O 0
% O 0
) O 0
. O 0

Patients O 0
were O 0
managed O 0
with O 0
cyclosporine B-Chemical 0
and O 0
azathioprine B-Chemical 0
. O 0

No O 0
prophylaxis O 0
with O 0
antilymphocyte O 0
globulin O 0
was O 0
used O 0
. O 0

Steroids B-Chemical 0
were O 0
given O 0
to O 0
39 O 0
% O 0
of O 0
patients O 0
for O 0
refractory O 0
rejection O 0
, O 0
but O 0
weaning O 0
was O 0
always O 0
attempted O 0
and O 0
generally O 0
successful O 0
( O 0
64 O 0
% O 0
) O 0
. O 0

Five O 0
patients O 0
( O 0
14 O 0
% O 0
) O 0
received O 0
maintenance O 0
steroids B-Chemical 0
. O 0

Four O 0
patients O 0
died O 0
in O 0
the O 0
perioperative O 0
period O 0
and O 0
one O 0
died O 0
4 O 0
months O 0
later O 0
. O 0

There O 0
have O 0
been O 0
no O 0
deaths O 0
related O 0
to O 0
rejection O 0
or O 0
infection B-Disease 0
. O 0

Average O 0
follow O 0
- O 0
up O 0
was O 0
36 O 0
+ O 0
/ O 0
- O 0
19 O 0
months O 0
( O 0
range O 0
1 O 0
to O 0
65 O 0
months O 0
) O 0
. O 0

Cumulative O 0
survival O 0
is O 0
88 O 0
% O 0
at O 0
5 O 0
years O 0
. O 0

In O 0
patients O 0
less O 0
than O 0
7 O 0
years O 0
of O 0
age O 0
, O 0
rejection O 0
was O 0
monitored O 0
noninvasively O 0
. O 0

In O 0
the O 0
first O 0
postoperative O 0
month O 0
, O 0
89 O 0
% O 0
of O 0
patients O 0
were O 0
treated O 0
for O 0
rejection O 0
. O 0

Freedom O 0
from O 0
serious O 0
infections B-Disease 0
was O 0
83 O 0
% O 0
at O 0
1 O 0
month O 0
and O 0
65 O 0
% O 0
at O 0
1 O 0
year O 0
. O 0

Cytomegalovirus B-Disease 0
infections I-Disease 0
were O 0
treated O 0
successfully O 0
with O 0
ganciclovir B-Chemical 0
in O 0
11 O 0
patients O 0
. O 0

No O 0
impairment O 0
of O 0
growth O 0
was O 0
observed O 0
in O 0
children O 0
who O 0
underwent O 0
transplantation O 0
compared O 0
with O 0
a O 0
control O 0
population O 0
. O 0

Twenty O 0
- O 0
one O 0
patients O 0
( O 0
60 O 0
% O 0
) O 0
have O 0
undergone O 0
annual O 0
catheterizations O 0
and O 0
no O 0
sign O 0
of O 0
graft O 0
atherosclerosis B-Disease 0
has O 0
been O 0
observed O 0
. O 0

Seizures B-Disease 0
occurred O 0
in O 0
five O 0
patients O 0
( O 0
14 O 0
% O 0
) O 0
and O 0
hypertension B-Disease 0
was O 0
treated O 0
in O 0
10 O 0
patients O 0
( O 0
28 O 0
% O 0
) O 0
. O 0

No O 0
patient O 0
was O 0
disabled O 0
and O 0
no O 0
lymphoproliferative B-Disease 0
disorder I-Disease 0
was O 0
observed O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Delirium B-Disease 0
during O 0
fluoxetine B-Chemical 0
treatment O 0
. O 0

A O 0
case O 0
report O 0
. O 0

The O 0
correlation O 0
between O 0
high O 0
serum O 0
tricyclic O 0
antidepressant O 0
concentrations O 0
and O 0
central O 0
nervous O 0
system O 0
side O 0
effects O 0
has O 0
been O 0
well O 0
established O 0
. O 0

Only O 0
a O 0
few O 0
reports O 0
exist O 0
, O 0
however O 0
, O 0
on O 0
the O 0
relationship O 0
between O 0
the O 0
serum O 0
concentrations O 0
of O 0
selective O 0
serotonin B-Chemical 0
reuptake O 0
inhibitors O 0
( O 0
SSRIs O 0
) O 0
and O 0
their O 0
toxic O 0
effects O 0
. O 0

In O 0
some O 0
cases O 0
, O 0
a O 0
high O 0
serum O 0
concentration O 0
of O 0
citalopram B-Chemical 0
( O 0
> O 0
600 O 0
nmol O 0
/ O 0
L O 0
) O 0
in O 0
elderly O 0
patients O 0
has O 0
been O 0
associated O 0
with O 0
increased O 0
somnolence B-Disease 0
and O 0
movement B-Disease 0
difficulties I-Disease 0
. O 0

Widespread O 0
cognitive B-Disease 0
disorders I-Disease 0
, O 0
such O 0
as O 0
delirium B-Disease 0
, O 0
have O 0
not O 0
been O 0
previously O 0
linked O 0
with O 0
high O 0
blood O 0
levels O 0
of O 0
SSRIs O 0
. O 0

In O 0
this O 0
report O 0
, O 0
we O 0
describe O 0
a O 0
patient O 0
with O 0
acute O 0
hyperkinetic B-Disease 0
delirium B-Disease 0
connected O 0
with O 0
a O 0
high O 0
serum O 0
total O 0
fluoxetine B-Chemical 0
( O 0
fluoxetine B-Chemical 0
plus O 0
desmethylfluoxetine B-Chemical 0
) O 0
concentration O 0
. O 0

Pulmonary B-Disease 0
edema I-Disease 0
and O 0
shock B-Disease 0
after O 0
high O 0
- O 0
dose O 0
aracytine B-Chemical 0
- I-Chemical 0
C I-Chemical 0
for O 0
lymphoma B-Disease 0
; O 0
possible O 0
role O 0
of O 0
TNF O 0
- O 0
alpha O 0
and O 0
PAF O 0
. O 0

Four O 0
out O 0
of O 0
23 O 0
consecutive O 0
patients O 0
treated O 0
with O 0
high O 0
- O 0
dose O 0
Ara B-Chemical 0
- I-Chemical 0
C I-Chemical 0
for O 0
lymphomas B-Disease 0
in O 0
our O 0
institution O 0
developed O 0
a O 0
strikingly O 0
similar O 0
syndrome O 0
during O 0
the O 0
perfusion O 0
. O 0

It O 0
was O 0
characterized O 0
by O 0
the O 0
onset O 0
of O 0
fever B-Disease 0
, O 0
diarrhea B-Disease 0
, O 0
shock B-Disease 0
, O 0
pulmonary B-Disease 0
edema I-Disease 0
, O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
, O 0
metabolic B-Disease 0
acidosis I-Disease 0
, O 0
weight B-Disease 0
gain I-Disease 0
and O 0
leukocytosis B-Disease 0
. O 0

Thorough O 0
bacteriological O 0
screening O 0
failed O 0
to O 0
provide O 0
evidence O 0
of O 0
infection B-Disease 0
. O 0

Sequential O 0
biological O 0
assays O 0
of O 0
IL O 0
- O 0
1 O 0
, O 0
IL O 0
- O 0
2 O 0
, O 0
TNF O 0
and O 0
PAF O 0
were O 0
performed O 0
during O 0
Ara B-Chemical 0
- I-Chemical 0
C I-Chemical 0
infusion O 0
to O 0
ten O 0
patients O 0
, O 0
including O 0
the O 0
four O 0
who O 0
developed O 0
the O 0
syndrome O 0
. O 0

TNF O 0
and O 0
PAF O 0
activity O 0
was O 0
found O 0
in O 0
the O 0
serum O 0
of O 0
respectively O 0
two O 0
and O 0
four O 0
of O 0
the O 0
cases O 0
, O 0
but O 0
not O 0
in O 0
the O 0
six O 0
controls O 0
. O 0

As O 0
TNF O 0
and O 0
PAF O 0
are O 0
thought O 0
to O 0
be O 0
involved O 0
in O 0
the O 0
development O 0
of O 0
septic O 0
shock B-Disease 0
and O 0
adult B-Disease 0
respiratory I-Disease 0
distress I-Disease 0
syndrome I-Disease 0
, O 0
we O 0
hypothesize O 0
that O 0
high O 0
- O 0
dose O 0
Ara B-Chemical 0
- I-Chemical 0
C I-Chemical 0
may O 0
be O 0
associated O 0
with O 0
cytokine O 0
release O 0
. O 0

Protective O 0
effect O 0
of O 0
clentiazem B-Chemical 0
against O 0
epinephrine B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
injury I-Disease 0
in O 0
rats O 0
. O 0

We O 0
investigated O 0
the O 0
effects O 0
of O 0
clentiazem B-Chemical 0
, O 0
a O 0
1 B-Chemical 0
, I-Chemical 0
5 I-Chemical 0
- I-Chemical 0
benzothiazepine I-Chemical 0
calcium B-Chemical 0
antagonist O 0
, O 0
on O 0
epinephrine B-Chemical 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
in O 0
rats O 0
. O 0

With O 0
2 O 0
- O 0
week O 0
chronic O 0
epinephrine B-Chemical 0
infusion O 0
, O 0
16 O 0
of O 0
30 O 0
rats O 0
died O 0
within O 0
4 O 0
days O 0
, O 0
and O 0
severe O 0
ischemic B-Disease 0
lesions I-Disease 0
and O 0
fibrosis B-Disease 0
of O 0
the O 0
left O 0
ventricles O 0
were O 0
observed O 0
. O 0

In O 0
epinephrine B-Chemical 0
- O 0
treated O 0
rats O 0
, O 0
left O 0
atrial O 0
and O 0
left O 0
ventricular O 0
papillary O 0
muscle O 0
contractile O 0
responses O 0
to O 0
isoproterenol B-Chemical 0
were O 0
reduced O 0
, O 0
but O 0
responses O 0
to O 0
calcium B-Chemical 0
were O 0
normal O 0
or O 0
enhanced O 0
compared O 0
to O 0
controls O 0
. O 0

Left O 0
ventricular O 0
alpha O 0
and O 0
beta O 0
adrenoceptor O 0
densities O 0
were O 0
also O 0
reduced O 0
compared O 0
to O 0
controls O 0
. O 0

Treatment O 0
with O 0
clentiazem B-Chemical 0
prevented O 0
epinephrine B-Chemical 0
- O 0
induced O 0
death O 0
( O 0
P O 0
< O 0
. O 0
05 O 0
) O 0
, O 0
and O 0
attenuated O 0
the O 0
ventricular O 0
ischemic B-Disease 0
lesions I-Disease 0
and O 0
fibrosis B-Disease 0
, O 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
manner O 0
. O 0

Left O 0
atrial O 0
and O 0
left O 0
ventricular O 0
papillary O 0
muscle O 0
contractile O 0
responses O 0
to O 0
isoproterenol B-Chemical 0
were O 0
reduced O 0
compared O 0
to O 0
controls O 0
in O 0
groups O 0
treated O 0
with O 0
clentiazem B-Chemical 0
alone O 0
, O 0
but O 0
combined O 0
with O 0
epinephrine B-Chemical 0
, O 0
clentiazem B-Chemical 0
restored O 0
left O 0
atrial O 0
responses O 0
and O 0
enhanced O 0
left O 0
ventricular O 0
papillary O 0
responses O 0
to O 0
isoproterenol B-Chemical 0
. O 0

On O 0
the O 0
other O 0
hand O 0
clentiazem B-Chemical 0
did O 0
not O 0
prevent O 0
epinephrine B-Chemical 0
- O 0
induced O 0
down O 0
- O 0
regulation O 0
of O 0
alpha O 0
and O 0
beta O 0
adrenoceptors O 0
. O 0

Interestingly O 0
, O 0
clentiazem B-Chemical 0
, O 0
infused O 0
alone O 0
, O 0
resulted O 0
in O 0
decreased O 0
adrenergic O 0
receptor O 0
densities O 0
in O 0
the O 0
left O 0
ventricle O 0
. O 0

Clentiazem B-Chemical 0
also O 0
did O 0
not O 0
prevent O 0
the O 0
enhanced O 0
responses O 0
to O 0
calcium B-Chemical 0
seen O 0
in O 0
the O 0
epinephrine B-Chemical 0
- O 0
treated O 0
animals O 0
, O 0
although O 0
the O 0
high O 0
dose O 0
of O 0
clentiazem B-Chemical 0
partially O 0
attenuated O 0
the O 0
maximal O 0
response O 0
to O 0
calcium B-Chemical 0
compared O 0
to O 0
epinephrine B-Chemical 0
- O 0
treated O 0
animals O 0
. O 0

In O 0
conclusion O 0
, O 0
clentiazem B-Chemical 0
attenuated O 0
epinephrine B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
injury I-Disease 0
, O 0
possibly O 0
through O 0
its O 0
effect O 0
on O 0
the O 0
adrenergic O 0
pathway O 0
. O 0

Kaliuretic O 0
effect O 0
of O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
treatment O 0
in O 0
parkinsonian B-Disease 0
patients O 0
. O 0

Hypokalemia B-Disease 0
, O 0
sometimes O 0
severe O 0
, O 0
was O 0
observed O 0
in O 0
some O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
- O 0
treated O 0
parkinsonian B-Disease 0
patients O 0
. O 0

The O 0
influence O 0
of O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
on O 0
the O 0
renal O 0
excretion O 0
of O 0
potassium B-Chemical 0
was O 0
studied O 0
in O 0
3 O 0
patients O 0
with O 0
hypokalemia B-Disease 0
and O 0
in O 0
5 O 0
normokalemic O 0
patients O 0
by O 0
determination O 0
of O 0
renal O 0
plasma O 0
flow O 0
, O 0
glomerular O 0
filtration O 0
rate O 0
, O 0
plasma O 0
concentration O 0
of O 0
potassium B-Chemical 0
and O 0
sodium B-Chemical 0
as O 0
well O 0
as O 0
urinary O 0
excretion O 0
of O 0
potassium B-Chemical 0
, O 0
sodium B-Chemical 0
and O 0
aldosterone B-Chemical 0
. O 0

L B-Chemical 0
- I-Chemical 0
Dopa I-Chemical 0
intake O 0
was O 0
found O 0
to O 0
cause O 0
an O 0
increased O 0
excretion O 0
of O 0
potassium B-Chemical 0
, O 0
and O 0
sometimes O 0
also O 0
of O 0
sodium B-Chemical 0
, O 0
in O 0
the O 0
hypokalemic O 0
but O 0
not O 0
in O 0
the O 0
normokalemic O 0
patients O 0
. O 0

This O 0
effect O 0
on O 0
the O 0
renal O 0
function O 0
could O 0
be O 0
prohibited O 0
by O 0
the O 0
administration O 0
of O 0
a O 0
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dopa O 0
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It O 0
is O 0
not O 0
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but O 0
not O 0
in O 0
others O 0
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but O 0
our O 0
results O 0
indicate O 0
a O 0
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aldosterone B-Chemical 0
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this O 0
renal O 0
effect O 0
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L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
. O 0

Cocaine B-Chemical 0
induced O 0
myocardial B-Disease 0
ischemia I-Disease 0
. O 0

We O 0
report O 0
a O 0
case O 0
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myocardial B-Disease 0
ischemia I-Disease 0
induced O 0
by O 0
cocaine B-Chemical 0
. O 0

The O 0
ischemia B-Disease 0
probably O 0
induced O 0
by O 0
coronary B-Disease 0
artery I-Disease 0
spasm I-Disease 0
was O 0
reversed O 0
by O 0
nitroglycerin B-Chemical 0
and O 0
calcium B-Chemical 0
blocking O 0
agents O 0
. O 0

Doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
monitored O 0
by O 0
ECG O 0
in O 0
freely O 0
moving O 0
mice O 0
. O 0

A O 0
new O 0
model O 0
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test O 0
potential O 0
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. O 0

In O 0
laboratory O 0
animals O 0
, O 0
histology O 0
is O 0
most O 0
commonly O 0
used O 0
to O 0
study O 0
doxorubicin B-Chemical 0
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induced O 0
cardiotoxicity B-Disease 0
. O 0

However O 0
, O 0
for O 0
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during O 0
treatment O 0
, O 0
large O 0
numbers O 0
of O 0
animals O 0
are O 0
needed O 0
. O 0

Recently O 0
we O 0
developed O 0
a O 0
new O 0
method O 0
to O 0
measure O 0
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values O 0
in O 0
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. O 0

With O 0
this O 0
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the O 0
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ICRF B-Chemical 0
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187 I-Chemical 0
as O 0
a O 0
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agent O 0
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The O 0
ST O 0
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0 O 0
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v O 0
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The O 0
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change O 0
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the O 0
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. O 0

After O 0
sacrifice O 0
the O 0
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doxorubicin B-Chemical 0
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animals O 0
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and O 0
the O 0
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. O 0

As O 0
this O 0
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exerted O 0
more O 0
toxicity B-Disease 0
than O 0
needed O 0
to O 0
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agents O 0
, O 0
the O 0
protection O 0
of O 0
ICRF B-Chemical 0
- I-Chemical 0
187 I-Chemical 0
was O 0
determined O 0
using O 0
a O 0
dose O 0
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with O 0
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toxicity B-Disease 0
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6 O 0
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of O 0
4 O 0
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. O 0

On O 0
this O 0
schedule O 0
, O 0
the O 0
animals O 0
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appeared O 0
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ICRF B-Chemical 0
- I-Chemical 0
187 I-Chemical 0
( O 0
50 O 0
mg O 0
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kg O 0
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i O 0
. O 0
p O 0
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1 O 0
h O 0
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doxorubicin B-Chemical 0
) O 0
provided O 0
almost O 0
full O 0
protection O 0
. O 0

These O 0
data O 0
were O 0
confirmed O 0
by O 0
histology O 0
. O 0

The O 0
results O 0
indicate O 0
that O 0
this O 0
new O 0
model O 0
is O 0
very O 0
sensitive O 0
and O 0
enables O 0
monitoring O 0
of O 0
the O 0
development O 0
of O 0
cardiotoxicity B-Disease 0
with O 0
time O 0
. O 0

These O 0
findings O 0
result O 0
in O 0
a O 0
model O 0
that O 0
allows O 0
the O 0
testing O 0
of O 0
protectors O 0
against O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
as O 0
demonstrated O 0
by O 0
the O 0
protection O 0
provided O 0
by O 0
ICRF B-Chemical 0
- I-Chemical 0
187 I-Chemical 0
. O 0

Epinephrine B-Chemical 0
dysrhythmogenicity O 0
is O 0
not O 0
enhanced O 0
by O 0
subtoxic O 0
bupivacaine B-Chemical 0
in O 0
dogs O 0
. O 0

Since O 0
bupivacaine B-Chemical 0
and O 0
epinephrine B-Chemical 0
may O 0
both O 0
precipitate O 0
dysrhythmias B-Disease 0
, O 0
circulating O 0
bupivacaine B-Chemical 0
during O 0
regional O 0
anesthesia O 0
could O 0
potentiate O 0
dysrhythmogenic O 0
effects O 0
of O 0
epinephrine B-Chemical 0
. O 0

We O 0
therefore O 0
examined O 0
whether O 0
bupivacaine B-Chemical 0
alters O 0
the O 0
dysrhythmogenicity O 0
of O 0
subsequent O 0
administration O 0
of O 0
epinephrine B-Chemical 0
in O 0
conscious O 0
, O 0
healthy O 0
dogs O 0
and O 0
in O 0
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myocardial B-Disease 0
infarction I-Disease 0
. O 0

Forty O 0
- O 0
one O 0
conscious O 0
dogs O 0
received O 0
10 O 0
micrograms O 0
. O 0
kg O 0
- O 0
1 O 0
. O 0
min O 0
- O 0
1 O 0
epinephrine B-Chemical 0
. O 0

Seventeen O 0
animals O 0
responded O 0
with O 0
ventricular B-Disease 0
tachycardia I-Disease 0
( O 0
VT B-Disease 0
) O 0
within O 0
3 O 0
min O 0
. O 0

After O 0
3 O 0
h O 0
, O 0
these O 0
responders O 0
randomly O 0
received O 0
1 O 0
or O 0
2 O 0
mg O 0
/ O 0
kg O 0
bupivacaine B-Chemical 0
or O 0
saline O 0
over O 0
5 O 0
min O 0
, O 0
followed O 0
by O 0
10 O 0
micrograms O 0
. O 0
kg O 0
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1 O 0
. O 0
min O 0
- O 0
1 O 0
epinephrine B-Chemical 0
. O 0

In O 0
the O 0
bupivacaine B-Chemical 0
groups O 0
, O 0
epinephrine B-Chemical 0
caused O 0
fewer O 0
prodysrhythmic O 0
effects O 0
than O 0
without O 0
bupivacaine B-Chemical 0
. O 0

VT B-Disease 0
appeared O 0
in O 0
fewer O 0
dogs O 0
and O 0
at O 0
a O 0
later O 0
time O 0
, O 0
and O 0
there O 0
were O 0
more O 0
sinoatrial O 0
beats O 0
and O 0
less O 0
ectopies O 0
. O 0

Epinephrine B-Chemical 0
shortened O 0
QT O 0
less O 0
after O 0
bupivacaine B-Chemical 0
than O 0
in O 0
control O 0
animals O 0
. O 0

One O 0
day O 0
after O 0
experimental O 0
myocardial B-Disease 0
infarction I-Disease 0
, O 0
six O 0
additional O 0
halothane B-Chemical 0
- O 0
anesthetized O 0
dogs O 0
received O 0
4 O 0
micrograms O 0
. O 0
kg O 0
- O 0
1 O 0
. O 0
min O 0
- O 0
1 O 0
epinephrine B-Chemical 0
until O 0
VT B-Disease 0
appeared O 0
. O 0

After O 0
45 O 0
min O 0
, O 0
1 O 0
mg O 0
/ O 0
kg O 0
bupivacaine B-Chemical 0
was O 0
injected O 0
over O 0
5 O 0
min O 0
, O 0
again O 0
followed O 0
by O 0
4 O 0
micrograms O 0
. O 0
kg O 0
- O 0
1 O 0
. O 0
min O 0
- O 0
1 O 0
epinephrine B-Chemical 0
. O 0

In O 0
these O 0
dogs O 0
, O 0
the O 0
prodysrhythmic O 0
response O 0
to O 0
epinephrine B-Chemical 0
was O 0
also O 0
mitigated O 0
by O 0
preceding O 0
bupivacaine B-Chemical 0
. O 0

Bupivacaine B-Chemical 0
antagonizes O 0
epinephrine B-Chemical 0
dysrhythmogenicity O 0
in O 0
conscious O 0
dogs O 0
susceptible O 0
to O 0
VT B-Disease 0
and O 0
in O 0
anesthetized O 0
dogs O 0
with O 0
spontaneous O 0
postinfarct O 0
dysrhythmias B-Disease 0
. O 0

There O 0
is O 0
no O 0
evidence O 0
that O 0
systemic O 0
subtoxic O 0
bupivacaine B-Chemical 0
administration O 0
enhances O 0
the O 0
dysrhythmogenicity O 0
of O 0
subsequent O 0
epinephrine B-Chemical 0
. O 0

Milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
induced O 0
by O 0
1 B-Chemical 0
, I-Chemical 0
25 I-Chemical 0
( I-Chemical 0
OH I-Chemical 0
) I-Chemical 0
2D I-Chemical 0
in O 0
a O 0
patient O 0
with O 0
hypoparathyroidism B-Disease 0
. O 0

Milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
was O 0
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described O 0
70 O 0
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ago O 0
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the O 0
context O 0
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the O 0
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of O 0
peptic B-Disease 0
ulcer I-Disease 0
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with O 0
large O 0
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calcium B-Chemical 0
and O 0
alkali B-Chemical 0
. O 0

Although O 0
with O 0
current O 0
ulcer B-Disease 0
therapy O 0
( O 0
H O 0
- O 0
2 O 0
blockers O 0
, O 0
omeprazole B-Chemical 0
, O 0
and O 0
sucralfate B-Chemical 0
) O 0
, O 0
the O 0
frequency O 0
of O 0
milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
has O 0
decreased O 0
significantly O 0
, O 0
the O 0
classic O 0
triad O 0
of O 0
hypercalcemia B-Disease 0
, O 0
alkalosis B-Disease 0
, O 0
and O 0
renal B-Disease 0
impairment I-Disease 0
remains O 0
the O 0
hallmark O 0
of O 0
the O 0
syndrome O 0
. O 0

Milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
can O 0
present O 0
serious O 0
and O 0
occasionally O 0
life O 0
- O 0
threatening O 0
illness O 0
unless O 0
diagnosed O 0
and O 0
treated O 0
appropriately O 0
. O 0

This O 0
article O 0
presents O 0
a O 0
patient O 0
with O 0
hypoparathyroidism B-Disease 0
who O 0
was O 0
treated O 0
with O 0
calcium B-Chemical 0
carbonate I-Chemical 0
and O 0
calcitriol B-Chemical 0
resulting O 0
in O 0
two O 0
admissions O 0
to O 0
the O 0
hospital O 0
for O 0
milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
. O 0

The O 0
patient O 0
was O 0
successfully O 0
treated O 0
with O 0
intravenous O 0
pamidronate B-Chemical 0
on O 0
his O 0
first O 0
admission O 0
and O 0
with O 0
hydrocortisone B-Chemical 0
on O 0
the O 0
second O 0
. O 0

This O 0
illustrates O 0
intravenous O 0
pamidronate B-Chemical 0
as O 0
a O 0
valuable O 0
therapeutic O 0
tool O 0
when O 0
milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
presents O 0
as O 0
hypercalcemic B-Disease 0
emergency I-Disease 0
. O 0

Famotidine B-Chemical 0
- O 0
associated O 0
delirium B-Disease 0
. O 0

A O 0
series O 0
of O 0
six O 0
cases O 0
. O 0

Famotidine B-Chemical 0
is O 0
a O 0
histamine O 0
H2 O 0
- O 0
receptor O 0
antagonist O 0
used O 0
in O 0
inpatient O 0
settings O 0
for O 0
prevention O 0
of O 0
stress O 0
ulcers B-Disease 0
and O 0
is O 0
showing O 0
increasing O 0
popularity O 0
because O 0
of O 0
its O 0
low O 0
cost O 0
. O 0

Although O 0
all O 0
of O 0
the O 0
currently O 0
available O 0
H2 O 0
- O 0
receptor O 0
antagonists O 0
have O 0
shown O 0
the O 0
propensity O 0
to O 0
cause O 0
delirium B-Disease 0
, O 0
only O 0
two O 0
previously O 0
reported O 0
cases O 0
have O 0
been O 0
associated O 0
with O 0
famotidine B-Chemical 0
. O 0

The O 0
authors O 0
report O 0
on O 0
six O 0
cases O 0
of O 0
famotidine B-Chemical 0
- O 0
associated O 0
delirium B-Disease 0
in O 0
hospitalized O 0
patients O 0
who O 0
cleared O 0
completely O 0
upon O 0
removal O 0
of O 0
famotidine B-Chemical 0
. O 0

The O 0
pharmacokinetics O 0
of O 0
famotidine B-Chemical 0
are O 0
reviewed O 0
, O 0
with O 0
no O 0
change O 0
in O 0
its O 0
metabolism O 0
in O 0
the O 0
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population O 0
seen O 0
. O 0

The O 0
implications O 0
of O 0
using O 0
famotidine B-Chemical 0
in O 0
elderly O 0
persons O 0
are O 0
discussed O 0
. O 0

Encephalopathy B-Disease 0
during O 0
amitriptyline B-Chemical 0
therapy O 0
: O 0
are O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
and O 0
serotonin B-Disease 0
syndrome I-Disease 0
spectrum O 0
disorders O 0
? O 0

This O 0
report O 0
describes O 0
a O 0
case O 0
of O 0
encephalopathy B-Disease 0
developed O 0
in O 0
the O 0
course O 0
of O 0
amitriptyline B-Chemical 0
therapy O 0
, O 0
during O 0
a O 0
remission O 0
of O 0
unipolar B-Disease 0
depression I-Disease 0
. O 0

This O 0
patient O 0
could O 0
have O 0
been O 0
diagnosed O 0
as O 0
having O 0
either O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
( O 0
NMS B-Disease 0
) O 0
or O 0
serotonin B-Disease 0
syndrome I-Disease 0
( O 0
SS B-Disease 0
) O 0
. O 0

The O 0
major O 0
determinant O 0
of O 0
the O 0
symptoms O 0
may O 0
have O 0
been O 0
dopamine B-Chemical 0
/ O 0
serotonin B-Chemical 0
imbalance O 0
in O 0
the O 0
central O 0
nervous O 0
system O 0
. O 0

The O 0
NMS B-Disease 0
- O 0
like O 0
encephalopathy B-Disease 0
that O 0
develops O 0
in O 0
association O 0
with O 0
the O 0
use O 0
of O 0
antidepressants O 0
indicates O 0
that O 0
NMS B-Disease 0
and O 0
SS B-Disease 0
are O 0
spectrum O 0
disorders O 0
induced O 0
by O 0
drugs O 0
with O 0
both O 0
antidopaminergic O 0
and O 0
serotonergic O 0
effects O 0
. O 0

Genetic O 0
separation O 0
of O 0
tumor B-Disease 0
growth O 0
and O 0
hemorrhagic B-Disease 0
phenotypes O 0
in O 0
an O 0
estrogen B-Chemical 0
- O 0
induced O 0
tumor B-Disease 0
. O 0

Chronic O 0
administration O 0
of O 0
estrogen B-Chemical 0
to O 0
the O 0
Fischer O 0
344 O 0
( O 0
F344 O 0
) O 0
rat O 0
induces O 0
growth O 0
of O 0
large O 0
, O 0
hemorrhagic B-Disease 0
pituitary B-Disease 0
tumors I-Disease 0
. O 0

Ten O 0
weeks O 0
of O 0
diethylstilbestrol B-Chemical 0
( O 0
DES B-Chemical 0
) O 0
treatment O 0
caused O 0
female O 0
F344 O 0
rat O 0
pituitaries O 0
to O 0
grow O 0
to O 0
an O 0
average O 0
of O 0
109 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
6 O 0
. O 0
3 O 0
mg O 0
( O 0
mean O 0
+ O 0
/ O 0
- O 0
SE O 0
) O 0
versus O 0
11 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
4 O 0
mg O 0
for O 0
untreated O 0
rats O 0
, O 0
and O 0
to O 0
become O 0
highly O 0
hemorrhagic B-Disease 0
. O 0

The O 0
same O 0
DES B-Chemical 0
treatment O 0
produced O 0
no O 0
significant O 0
growth O 0
( O 0
8 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
5 O 0
mg O 0
for O 0
treated O 0
females O 0
versus O 0
8 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
1 O 0
for O 0
untreated O 0
females O 0
) O 0
or O 0
morphological O 0
changes O 0
in O 0
Brown O 0
Norway O 0
( O 0
BN O 0
) O 0
rat O 0
pituitaries O 0
. O 0

An O 0
F1 O 0
hybrid O 0
of O 0
F344 O 0
and O 0
BN O 0
exhibited O 0
significant O 0
pituitary O 0
growth O 0
after O 0
10 O 0
weeks O 0
of O 0
DES B-Chemical 0
treatment O 0
with O 0
an O 0
average O 0
mass O 0
of O 0
26 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
7 O 0
mg O 0
compared O 0
with O 0
8 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
9 O 0
mg O 0
for O 0
untreated O 0
rats O 0
. O 0

Surprisingly O 0
, O 0
the O 0
F1 O 0
hybrid O 0
tumors B-Disease 0
were O 0
not O 0
hemorrhagic B-Disease 0
and O 0
had O 0
hemoglobin O 0
content O 0
and O 0
outward O 0
appearance O 0
identical O 0
to O 0
that O 0
of O 0
BN O 0
. O 0

Expression O 0
of O 0
both O 0
growth O 0
and O 0
morphological O 0
changes O 0
is O 0
due O 0
to O 0
multiple O 0
genes O 0
. O 0

However O 0
, O 0
while O 0
DES B-Chemical 0
- O 0
induced O 0
pituitary O 0
growth O 0
exhibited O 0
quantitative O 0
, O 0
additive O 0
inheritance O 0
, O 0
the O 0
hemorrhagic B-Disease 0
phenotype O 0
exhibited O 0
recessive O 0
, O 0
epistatic O 0
inheritance O 0
. O 0

Only O 0
5 O 0
of O 0
the O 0
160 O 0
F2 O 0
pituitaries O 0
exhibited O 0
the O 0
hemorrhagic B-Disease 0
phenotype O 0
; O 0
36 O 0
of O 0
the O 0
160 O 0
F2 O 0
pituitaries O 0
were O 0
in O 0
the O 0
F344 O 0
range O 0
of O 0
mass O 0
, O 0
but O 0
31 O 0
of O 0
these O 0
were O 0
not O 0
hemorrhagic B-Disease 0
, O 0
indicating O 0
that O 0
the O 0
hemorrhagic B-Disease 0
phenotype O 0
is O 0
not O 0
merely O 0
a O 0
consequence O 0
of O 0
extensive O 0
growth O 0
. O 0

The O 0
hemorrhagic B-Disease 0
F2 O 0
pituitaries O 0
were O 0
all O 0
among O 0
the O 0
most O 0
massive O 0
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indicating O 0
that O 0
some O 0
of O 0
the O 0
genes O 0
regulate O 0
both O 0
phenotypes O 0
. O 0

Increased O 0
expression O 0
of O 0
neuronal O 0
nitric B-Chemical 0
oxide I-Chemical 0
synthase O 0
in O 0
bladder O 0
afferent O 0
pathways O 0
following O 0
chronic O 0
bladder B-Disease 0
irritation I-Disease 0
. O 0

Immunocytochemical O 0
techniques O 0
were O 0
used O 0
to O 0
examine O 0
alterations O 0
in O 0
the O 0
expression O 0
of O 0
neuronal O 0
nitric B-Chemical 0
oxide I-Chemical 0
synthase O 0
( O 0
NOS O 0
) O 0
in O 0
bladder O 0
pathways O 0
following O 0
acute O 0
and O 0
chronic O 0
irritation B-Disease 0
of I-Disease 0
the I-Disease 0
urinary I-Disease 0
tract I-Disease 0
of O 0
the O 0
rat O 0
. O 0

Chemical O 0
cystitis B-Disease 0
was O 0
induced O 0
by O 0
cyclophosphamide B-Chemical 0
( O 0
CYP B-Chemical 0
) O 0
which O 0
is O 0
metabolized O 0
to O 0
acrolein B-Chemical 0
, O 0
an O 0
irritant O 0
eliminated O 0
in O 0
the O 0
urine O 0
. O 0

Injection O 0
of O 0
CYP B-Chemical 0
( O 0
n O 0
= O 0
10 O 0
, O 0
75 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
2 O 0
hours O 0
prior O 0
to O 0
perfusion O 0
( O 0
acute O 0
treatment O 0
) O 0
of O 0
the O 0
animals O 0
increased O 0
Fos O 0
- O 0
immunoreactivity O 0
( O 0
IR O 0
) O 0
in O 0
neurons O 0
in O 0
the O 0
dorsal O 0
commissure O 0
, O 0
dorsal O 0
horn O 0
, O 0
and O 0
autonomic O 0
regions O 0
of O 0
spinal O 0
segments O 0
( O 0
L1 O 0
- O 0
L2 O 0
and O 0
L6 O 0
- O 0
S1 O 0
) O 0
which O 0
receive O 0
afferent O 0
inputs O 0
from O 0
the O 0
bladder O 0
, O 0
urethra O 0
, O 0
and O 0
ureter O 0
. O 0

Fos O 0
- O 0
IR O 0
in O 0
the O 0
spinal O 0
cord O 0
was O 0
not O 0
changed O 0
in O 0
rats O 0
receiving O 0
chronic O 0
CYP B-Chemical 0
treatment O 0
( O 0
n O 0
= O 0
15 O 0
, O 0
75 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
, O 0
every O 0
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day O 0
for O 0
2 O 0
weeks O 0
) O 0
. O 0

In O 0
control O 0
animals O 0
and O 0
in O 0
animals O 0
treated O 0
acutely O 0
with O 0
CYP B-Chemical 0
, O 0
only O 0
small O 0
numbers O 0
of O 0
NOS O 0
- O 0
IR O 0
cells O 0
( O 0
0 O 0
. O 0
5 O 0
- O 0
0 O 0
. O 0
7 O 0
cell O 0
profiles O 0
/ O 0
sections O 0
) O 0
were O 0
detected O 0
in O 0
the O 0
L6 O 0
- O 0
S1 O 0
dorsal O 0
root O 0
ganglia O 0
( O 0
DRG O 0
) O 0
. O 0

Chronic O 0
CYP B-Chemical 0
administration O 0
significantly O 0
( O 0
P O 0
< O 0
or O 0
= O 0
. O 0
002 O 0
) O 0
increased O 0
bladder O 0
weight O 0
by O 0
60 O 0
% O 0
and O 0
increased O 0
( O 0
7 O 0
- O 0
to O 0
11 O 0
- O 0
fold O 0
) O 0
the O 0
numbers O 0
of O 0
NOS O 0
- O 0
immunoreactive O 0
( O 0
IR O 0
) O 0
afferent O 0
neurons O 0
in O 0
the O 0
L6 O 0
- O 0
S1 O 0
DRG O 0
. O 0

A O 0
small O 0
increase O 0
( O 0
1 O 0
. O 0
5 O 0
- O 0
fold O 0
) O 0
also O 0
occurred O 0
in O 0
the O 0
L1 O 0
DRG O 0
, O 0
but O 0
no O 0
change O 0
was O 0
detected O 0
in O 0
the O 0
L2 O 0
and O 0
L5 O 0
DRG O 0
. O 0

Bladder O 0
afferent O 0
cells O 0
in O 0
the O 0
L6 O 0
- O 0
S1 O 0
DRG O 0
labeled O 0
by O 0
Fluorogold O 0
( O 0
40 O 0
microliters O 0
) O 0
injected O 0
into O 0
the O 0
bladder O 0
wall O 0
did O 0
not O 0
exhibit O 0
NOS O 0
- O 0
IR O 0
in O 0
control O 0
animals O 0
; O 0
however O 0
, O 0
following O 0
chronic O 0
CYP B-Chemical 0
administration O 0
, O 0
a O 0
significant O 0
percentage O 0
of O 0
bladder O 0
afferent O 0
neurons O 0
were O 0
NOS O 0
- O 0
IR O 0
: O 0
L6 O 0
( O 0
19 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
6 O 0
% O 0
) O 0
and O 0
S1 O 0
( O 0
25 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
9 O 0
% O 0
) O 0
. O 0

These O 0
results O 0
indicate O 0
that O 0
neuronal O 0
gene O 0
expression O 0
in O 0
visceral O 0
sensory O 0
pathways O 0
can O 0
be O 0
upregulated O 0
by O 0
chemical O 0
irritation O 0
of O 0
afferent O 0
receptors O 0
in O 0
the O 0
urinary O 0
tract O 0
and O 0
/ O 0
or O 0
that O 0
pathological O 0
changes O 0
in O 0
the O 0
urinary O 0
tract O 0
can O 0
initiate O 0
chemical O 0
signals O 0
that O 0
alter O 0
the O 0
chemical O 0
properties O 0
of O 0
visceral O 0
afferent O 0
neurons O 0
. O 0

Effects O 0
of O 0
a O 0
new O 0
calcium B-Chemical 0
antagonist O 0
, O 0
CD B-Chemical 0
- I-Chemical 0
832 I-Chemical 0
, O 0
on O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
myocardial B-Disease 0
ischemia I-Disease 0
in O 0
dogs O 0
with O 0
partial O 0
coronary B-Disease 0
stenosis I-Disease 0
. O 0

Effects O 0
of O 0
CD B-Chemical 0
- I-Chemical 0
832 I-Chemical 0
on O 0
isoproterenol B-Chemical 0
( O 0
ISO B-Chemical 0
) O 0
- O 0
induced O 0
myocardial B-Disease 0
ischemia I-Disease 0
were O 0
studied O 0
in O 0
dogs O 0
with O 0
partial O 0
coronary B-Disease 0
stenosis I-Disease 0
of O 0
the O 0
left O 0
circumflex O 0
coronary O 0
artery O 0
and O 0
findings O 0
were O 0
compared O 0
with O 0
those O 0
for O 0
nifedipine B-Chemical 0
or O 0
diltiazem B-Chemical 0
. O 0

In O 0
the O 0
presence O 0
of O 0
coronary B-Disease 0
artery I-Disease 0
stenosis I-Disease 0
, O 0
3 O 0
- O 0
min O 0
periods O 0
of O 0
intracoronary O 0
ISO B-Chemical 0
infusion O 0
( O 0
10 O 0
ng O 0
/ O 0
kg O 0
/ O 0
min O 0
) O 0
increased O 0
heart O 0
rate O 0
and O 0
maximal O 0
rate O 0
of O 0
left O 0
ventricular O 0
pressure O 0
rise O 0
, O 0
which O 0
resulted O 0
in O 0
a O 0
decrease O 0
in O 0
percentage O 0
segmental O 0
shortening O 0
and O 0
ST O 0
- O 0
segment O 0
elevation O 0
of O 0
the O 0
epicardial O 0
electrocardiogram O 0
. O 0

After O 0
the O 0
control O 0
ISO B-Chemical 0
infusion O 0
with O 0
stenosis B-Disease 0
was O 0
performed O 0
, O 0
equihypotensive O 0
doses O 0
of O 0
CD B-Chemical 0
- I-Chemical 0
832 I-Chemical 0
( O 0
3 O 0
and O 0
10 O 0
micrograms O 0
/ O 0
kg O 0
/ O 0
min O 0
, O 0
n O 0
= O 0
7 O 0
) O 0
, O 0
nifedipine B-Chemical 0
( O 0
1 O 0
and O 0
3 O 0
micrograms O 0
/ O 0
kg O 0
/ O 0
min O 0
, O 0
n O 0
= O 0
9 O 0
) O 0
or O 0
diltiazem B-Chemical 0
( O 0
10 O 0
and O 0
30 O 0
micrograms O 0
/ O 0
kg O 0
/ O 0
min O 0
, O 0
n O 0
= O 0
7 O 0
) O 0
were O 0
infused O 0
5 O 0
min O 0
before O 0
and O 0
during O 0
the O 0
second O 0
and O 0
third O 0
ISO B-Chemical 0
infusion O 0
. O 0

Both O 0
CD B-Chemical 0
- I-Chemical 0
832 I-Chemical 0
and O 0
diltiazem B-Chemical 0
, O 0
but O 0
not O 0
nifedipine B-Chemical 0
, O 0
significantly O 0
reduced O 0
the O 0
increase O 0
in O 0
heart O 0
rate O 0
induced O 0
by O 0
ISO B-Chemical 0
infusion O 0
. O 0

In O 0
contrast O 0
to O 0
nifedipine B-Chemical 0
, O 0
CD B-Chemical 0
- I-Chemical 0
832 I-Chemical 0
( O 0
10 O 0
micrograms O 0
/ O 0
kg O 0
/ O 0
min O 0
) O 0
prevented O 0
the O 0
decrease O 0
in O 0
percentage O 0
segmental O 0
shortening O 0
from O 0
32 O 0
+ O 0
/ O 0
- O 0
12 O 0
% O 0
to O 0
115 O 0
+ O 0
/ O 0
- O 0
26 O 0
% O 0
of O 0
the O 0
control O 0
value O 0
( O 0
P O 0
< O 0
. O 0
01 O 0
) O 0
and O 0
ST O 0
- O 0
segment O 0
elevation O 0
from O 0
5 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
0 O 0
mV O 0
to O 0
1 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
3 O 0
mV O 0
( O 0
P O 0
< O 0
. O 0
01 O 0
) O 0
at O 0
3 O 0
min O 0
after O 0
ISO B-Chemical 0
infusion O 0
with O 0
stenosis B-Disease 0
. O 0

Diltiazem B-Chemical 0
( O 0
30 O 0
micrograms O 0
/ O 0
kg O 0
/ O 0
min O 0
) O 0
also O 0
prevented O 0
the O 0
decrease O 0
in O 0
percentage O 0
segmental O 0
shortening O 0
from O 0
34 O 0
+ O 0
/ O 0
- O 0
14 O 0
% O 0
to O 0
63 O 0
+ O 0
/ O 0
- O 0
18 O 0
% O 0
of O 0
the O 0
control O 0
value O 0
( O 0
P O 0
< O 0
. O 0
05 O 0
) O 0
and O 0
ST O 0
- O 0
segment O 0
elevation O 0
from O 0
4 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
7 O 0
mV O 0
to O 0
2 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
7 O 0
mV O 0
( O 0
P O 0
< O 0
. O 0
01 O 0
) O 0
at O 0
3 O 0
min O 0
after O 0
ISO B-Chemical 0
infusion O 0
with O 0
stenosis B-Disease 0
. O 0

These O 0
data O 0
show O 0
that O 0
CD B-Chemical 0
- I-Chemical 0
832 I-Chemical 0
improves O 0
myocardial B-Disease 0
ischemia I-Disease 0
during O 0
ISO B-Chemical 0
infusion O 0
with O 0
stenosis B-Disease 0
and O 0
suggest O 0
that O 0
the O 0
negative O 0
chronotropic O 0
property O 0
of O 0
CD B-Chemical 0
- I-Chemical 0
832 I-Chemical 0
plays O 0
a O 0
major O 0
role O 0
in O 0
the O 0
beneficial O 0
effects O 0
of O 0
CD B-Chemical 0
- I-Chemical 0
832 I-Chemical 0
. O 0

The O 0
effect O 0
of O 0
recombinant O 0
human O 0
insulin O 0
- O 0
like O 0
growth O 0
factor O 0
- O 0
I O 0
on O 0
chronic O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
nephropathy B-Disease 0
in O 0
rats O 0
. O 0

We O 0
recently O 0
demonstrated O 0
that O 0
recombinant O 0
hGH O 0
exacerbates O 0
renal O 0
functional O 0
and O 0
structural O 0
injury O 0
in O 0
chronic O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
( O 0
PAN B-Chemical 0
) O 0
nephropathy B-Disease 0
, O 0
an O 0
experimental O 0
model O 0
of O 0
glomerular B-Disease 0
disease I-Disease 0
. O 0

Therefore O 0
, O 0
we O 0
examined O 0
whether O 0
recombinant O 0
human O 0
( O 0
rh O 0
) O 0
IGF O 0
- O 0
I O 0
is O 0
a O 0
safer O 0
alternative O 0
for O 0
the O 0
treatment O 0
of O 0
growth B-Disease 0
failure I-Disease 0
in O 0
rats O 0
with O 0
chronic O 0
PAN B-Chemical 0
nephropathy B-Disease 0
. O 0

The O 0
glomerulopathy B-Disease 0
was O 0
induced O 0
by O 0
seven O 0
serial O 0
injections O 0
of O 0
PAN B-Chemical 0
over O 0
12 O 0
wk O 0
. O 0

Experimental O 0
animals O 0
( O 0
n O 0
= O 0
6 O 0
) O 0
received O 0
rhIGF O 0
- O 0
I O 0
, O 0
400 O 0
micrograms O 0
/ O 0
d O 0
, O 0
whereas O 0
control O 0
rats O 0
( O 0
n O 0
= O 0
6 O 0
) O 0
received O 0
the O 0
vehicle O 0
. O 0

rhIGF O 0
- O 0
I O 0
improved O 0
weight O 0
gain O 0
by O 0
14 O 0
% O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
, O 0
without O 0
altering O 0
hematocrit O 0
or O 0
blood O 0
pressure O 0
in O 0
rats O 0
with O 0
renal B-Disease 0
disease I-Disease 0
. O 0

Urinary O 0
protein O 0
excretion O 0
was O 0
unaltered O 0
by O 0
rhIGF O 0
- O 0
I O 0
treatment O 0
in O 0
rats O 0
with O 0
chronic O 0
PAN B-Chemical 0
nephropathy B-Disease 0
. O 0

After O 0
12 O 0
wk O 0
, O 0
the O 0
inulin O 0
clearance O 0
was O 0
higher O 0
in O 0
rhIGF O 0
- O 0
I O 0
- O 0
treated O 0
rats O 0
, O 0
0 O 0
. O 0
48 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
08 O 0
versus O 0
0 O 0
. O 0
24 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
06 O 0
mL O 0
/ O 0
min O 0
/ O 0
100 O 0
g O 0
of O 0
body O 0
weight O 0
in O 0
untreated O 0
PAN B-Chemical 0
nephropathy B-Disease 0
animals O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
. O 0

The O 0
improvement O 0
in O 0
GFR O 0
was O 0
not O 0
associated O 0
with O 0
enhanced O 0
glomerular B-Disease 0
hypertrophy I-Disease 0
or O 0
increased O 0
segmental O 0
glomerulosclerosis B-Disease 0
, O 0
tubulointerstitial B-Disease 0
injury I-Disease 0
, O 0
or O 0
renal O 0
cortical O 0
malondialdehyde B-Chemical 0
content O 0
. O 0

In O 0
rats O 0
with O 0
PAN B-Chemical 0
nephropathy B-Disease 0
, O 0
administration O 0
of O 0
rhIGF O 0
- O 0
I O 0
increased O 0
IGF O 0
- O 0
I O 0
and O 0
GH O 0
receptor O 0
gene O 0
expression O 0
, O 0
without O 0
altering O 0
the O 0
steady O 0
state O 0
level O 0
of O 0
IGF O 0
- O 0
I O 0
receptor O 0
mRNA O 0
. O 0

In O 0
normal O 0
rats O 0
with O 0
intact O 0
kidneys O 0
, O 0
rhIGF O 0
- O 0
I O 0
administration O 0
( O 0
n O 0
= O 0
4 O 0
) O 0
did O 0
not O 0
alter O 0
weight O 0
gain O 0
, O 0
blood O 0
pressure O 0
, O 0
proteinuria B-Disease 0
, O 0
GFR O 0
, O 0
glomerular O 0
planar O 0
area O 0
, O 0
renal O 0
cortical O 0
malondialdehyde B-Chemical 0
content O 0
, O 0
or O 0
glomerular O 0
or O 0
tubulointerstitial B-Disease 0
damage I-Disease 0
, O 0
compared O 0
with O 0
untreated O 0
animals O 0
( O 0
n O 0
= O 0
4 O 0
) O 0
. O 0

rhIGF O 0
- O 0
I O 0
treatment O 0
reduced O 0
the O 0
steady O 0
state O 0
renal O 0
IGF O 0
- O 0
I O 0
mRNA O 0
level O 0
but O 0
did O 0
not O 0
modify O 0
gene O 0
expression O 0
of O 0
the O 0
IGF O 0
- O 0
I O 0
or O 0
GH O 0
receptors O 0
. O 0

We O 0
conclude O 0
that O 0
: O 0
1 O 0
) O 0
administration O 0
of O 0
rhIGF O 0
- O 0
I O 0
improves O 0
growth O 0
and O 0
GFR O 0
in O 0
rats O 0
with O 0
chronic O 0
PAN B-Chemical 0
nephropathy B-Disease 0
and O 0
2 O 0
) O 0
unlike O 0
rhGH O 0
, O 0
long O 0
- O 0
term O 0
use O 0
of O 0
rhIGF O 0
- O 0
I O 0
does O 0
not O 0
worsen O 0
renal O 0
functional O 0
and O 0
structural O 0
injury O 0
in O 0
this O 0
disease O 0
model O 0
. O 0

Nefiracetam B-Chemical 0
( O 0
DM B-Chemical 0
- I-Chemical 0
9384 I-Chemical 0
) O 0
reverses O 0
apomorphine B-Chemical 0
- O 0
induced O 0
amnesia B-Disease 0
of O 0
a O 0
passive O 0
avoidance O 0
response O 0
: O 0
delayed O 0
emergence O 0
of O 0
the O 0
memory O 0
retention O 0
effects O 0
. O 0

Nefiracetam B-Chemical 0
is O 0
a O 0
novel O 0
pyrrolidone B-Chemical 0
derivative O 0
which O 0
attenuates O 0
scopolamine B-Chemical 0
- O 0
induced O 0
learning B-Disease 0
and I-Disease 0
post I-Disease 0
- I-Disease 0
training I-Disease 0
consolidation I-Disease 0
deficits I-Disease 0
. O 0

Given O 0
that O 0
apomorphine B-Chemical 0
inhibits O 0
passive O 0
avoidance O 0
retention O 0
when O 0
given O 0
during O 0
training O 0
or O 0
in O 0
a O 0
defined O 0
10 O 0
- O 0
12h O 0
post O 0
- O 0
training O 0
period O 0
, O 0
we O 0
evaluated O 0
the O 0
ability O 0
of O 0
nefiracetam B-Chemical 0
to O 0
attenuate O 0
amnesia B-Disease 0
induced O 0
by O 0
dopaminergic O 0
agonism O 0
. O 0

A O 0
step O 0
- O 0
down O 0
passive O 0
avoidance O 0
paradigm O 0
was O 0
employed O 0
and O 0
nefiracetam B-Chemical 0
( O 0
3 O 0
mg O 0
/ O 0
kg O 0
) O 0
and O 0
apomorphine B-Chemical 0
( O 0
0 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
were O 0
given O 0
alone O 0
or O 0
in O 0
combination O 0
during O 0
training O 0
and O 0
at O 0
the O 0
10 O 0
- O 0
12h O 0
post O 0
- O 0
training O 0
period O 0
of O 0
consolidation O 0
. O 0

Co O 0
- O 0
administration O 0
of O 0
nefiracetam B-Chemical 0
and O 0
apomorphine B-Chemical 0
during O 0
training O 0
or O 0
10h O 0
thereafter O 0
produced O 0
no O 0
significant O 0
anti O 0
- O 0
amnesic O 0
effect O 0
. O 0

However O 0
, O 0
administration O 0
of O 0
nefiracetam B-Chemical 0
during O 0
training O 0
completely O 0
reversed O 0
the O 0
amnesia B-Disease 0
induced O 0
by O 0
apomorphine B-Chemical 0
at O 0
the O 0
10h O 0
post O 0
- O 0
training O 0
time O 0
and O 0
the O 0
converse O 0
was O 0
also O 0
true O 0
. O 0

These O 0
effects O 0
were O 0
not O 0
mediated O 0
by O 0
a O 0
dopaminergic O 0
mechanism O 0
as O 0
nefiracetam B-Chemical 0
, O 0
at O 0
millimolar O 0
concentrations O 0
, O 0
failed O 0
to O 0
displace O 0
either O 0
[ O 0
3H O 0
] O 0
SCH B-Chemical 0
23390 I-Chemical 0
or O 0
[ O 0
3H O 0
] O 0
spiperone B-Chemical 0
binding O 0
from O 0
D1 O 0
or O 0
D2 O 0
dopamine B-Chemical 0
receptor O 0
subtypes O 0
, O 0
respectively O 0
. O 0

It O 0
is O 0
suggested O 0
that O 0
nefiracetam B-Chemical 0
augments O 0
molecular O 0
processes O 0
in O 0
the O 0
early O 0
stages O 0
of O 0
events O 0
which O 0
ultimately O 0
lead O 0
to O 0
consolidation O 0
of O 0
memory O 0
. O 0

Phenytoin B-Chemical 0
encephalopathy B-Disease 0
as O 0
probable O 0
idiosyncratic O 0
reaction O 0
: O 0
case O 0
report O 0
. O 0

A O 0
case O 0
of O 0
phenytoin B-Chemical 0
( O 0
DPH B-Chemical 0
) O 0
encephalopathy B-Disease 0
with O 0
increasing O 0
seizures B-Disease 0
and O 0
EEG O 0
and O 0
mental O 0
changes O 0
is O 0
described O 0
. O 0

Despite O 0
adequate O 0
oral O 0
dosage O 0
of O 0
DPH B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
/ O 0
daily O 0
) O 0
the O 0
plasma O 0
level O 0
was O 0
very O 0
low O 0
( O 0
2 O 0
. O 0
8 O 0
microgramg O 0
/ O 0
ml O 0
) O 0
. O 0

The O 0
encephalopathy B-Disease 0
was O 0
probably O 0
an O 0
idiosyncratic O 0
and O 0
not O 0
toxic O 0
or O 0
allergic O 0
reaction O 0
. O 0

In O 0
fact O 0
the O 0
concentration O 0
of O 0
free O 0
DPH B-Chemical 0
was O 0
normal O 0
, O 0
the O 0
patient O 0
presented O 0
a O 0
retarded O 0
morbilliform O 0
rash B-Disease 0
during O 0
DPH B-Chemical 0
treatment O 0
, O 0
the O 0
protidogram O 0
was O 0
normal O 0
, O 0
and O 0
an O 0
intradermic O 0
DPH B-Chemical 0
injection O 0
had O 0
no O 0
local O 0
effect O 0
. O 0

The O 0
authors O 0
conclude O 0
that O 0
in O 0
a O 0
patient O 0
starting O 0
DPH B-Chemical 0
treatment O 0
an O 0
unexpected O 0
increase O 0
in O 0
seizures B-Disease 0
, O 0
with O 0
EEG O 0
and O 0
mental O 0
changes O 0
occurring O 0
simultaneously O 0
, O 0
should O 0
alert O 0
the O 0
physician O 0
to O 0
the O 0
possible O 0
need O 0
for O 0
eliminating O 0
DPH B-Chemical 0
from O 0
the O 0
therapeutic O 0
regimen O 0
, O 0
even O 0
if O 0
plasma O 0
concentrations O 0
are O 0
low O 0
. O 0

Prevention O 0
and O 0
treatment O 0
of O 0
endometrial B-Disease 0
disease I-Disease 0
in O 0
climacteric O 0
women O 0
receiving O 0
oestrogen B-Chemical 0
therapy O 0
. O 0

The O 0
treatment O 0
regimens O 0
are O 0
described O 0
in O 0
74 O 0
patients O 0
with O 0
endometrial B-Disease 0
disease I-Disease 0
among O 0
850 O 0
climacteric O 0
women O 0
receiving O 0
oestrogen B-Chemical 0
therapy O 0
. O 0

Cystic O 0
hyperplasia B-Disease 0
was O 0
associated O 0
with O 0
unopposed O 0
oestrogen B-Chemical 0
therapy O 0
without O 0
progestagen B-Chemical 0
. O 0

Two O 0
courses O 0
of O 0
21 O 0
days O 0
of O 0
5 O 0
mg O 0
norethisterone B-Chemical 0
daily O 0
caused O 0
reversion O 0
to O 0
normal O 0
in O 0
all O 0
57 O 0
cases O 0
of O 0
cystic O 0
hyperplasia B-Disease 0
and O 0
6 O 0
of O 0
the O 0
8 O 0
cases O 0
of O 0
atypical O 0
hyperplasia B-Disease 0
. O 0

4 O 0
cases O 0
of O 0
endometrial B-Disease 0
carcinoma I-Disease 0
referred O 0
from O 0
elsewhere O 0
demonstrated O 0
the O 0
problems O 0
of O 0
inappropriate O 0
and O 0
unsupervised O 0
unopposed O 0
oestrogen B-Chemical 0
therapy O 0
and O 0
the O 0
difficulty O 0
in O 0
distinguishing O 0
severe O 0
hyperplasia B-Disease 0
from O 0
malignancy B-Disease 0
. O 0

Cyclical O 0
low O 0
- O 0
dose O 0
oestrogen B-Chemical 0
therapy O 0
with O 0
7 O 0
- O 0
- O 0
13 O 0
days O 0
of O 0
progestagen B-Chemical 0
does O 0
not O 0
seem O 0
to O 0
increase O 0
the O 0
risk O 0
of O 0
endometrial B-Disease 0
hyperplasia I-Disease 0
or O 0
carcinoma B-Disease 0
. O 0

Effects O 0
of O 0
exercise O 0
on O 0
the O 0
severity O 0
of O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

The O 0
effect O 0
of O 0
exercise O 0
on O 0
the O 0
severity O 0
of O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
myocardial B-Disease 0
infarction I-Disease 0
was O 0
studied O 0
in O 0
male O 0
rats O 0
. O 0

Ninety O 0
- O 0
three O 0
rats O 0
were O 0
randomly O 0
divided O 0
into O 0
three O 0
groups O 0
. O 0

The O 0
exercise O 0
- O 0
isoproterenol B-Chemical 0
( O 0
E O 0
- O 0
1 O 0
) O 0
and O 0
exercise O 0
control O 0
( O 0
EC O 0
) O 0
groups O 0
exercised O 0
daily O 0
for O 0
thirty O 0
days O 0
on O 0
a O 0
treadmill O 0
at O 0
1 O 0
mph O 0
, O 0
2 O 0
% O 0
grade O 0
while O 0
animals O 0
of O 0
the O 0
sedentary O 0
- O 0
isoproterenol B-Chemical 0
( O 0
S O 0
- O 0
I O 0
) O 0
group O 0
remained O 0
sedentary O 0
. O 0

Eight O 0
animals O 0
were O 0
assigned O 0
to O 0
the O 0
sedentary O 0
control O 0
( O 0
SC O 0
) O 0
group O 0
which O 0
remained O 0
sedentary O 0
throughout O 0
the O 0
experimental O 0
period O 0
. O 0

Forty O 0
- O 0
eight O 0
hours O 0
after O 0
the O 0
final O 0
exercise O 0
period O 0
, O 0
S O 0
- O 0
I O 0
and O 0
E O 0
- O 0
I O 0
animals O 0
received O 0
a O 0
single O 0
subcutaneous O 0
injection O 0
of O 0
isoproterenol B-Chemical 0
( O 0
250 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
) O 0
. O 0

Animals O 0
of O 0
the O 0
S O 0
- O 0
I O 0
group O 0
exhibited O 0
significantly O 0
( O 0
Pp O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
greater O 0
mortality O 0
from O 0
the O 0
effects O 0
of O 0
isoproterenol B-Chemical 0
than O 0
animals O 0
of O 0
the O 0
E O 0
- O 0
I O 0
group O 0
. O 0

Serum O 0
CPK O 0
activity O 0
for O 0
E O 0
- O 0
I O 0
animals O 0
was O 0
significantly O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
greater O 0
than O 0
for O 0
animals O 0
in O 0
the O 0
S O 0
- O 0
I O 0
and O 0
EC O 0
groups O 0
twenty O 0
hours O 0
following O 0
isoproterenol B-Chemical 0
injection O 0
. O 0

No O 0
statistically O 0
significant O 0
differences O 0
were O 0
observed O 0
between O 0
the O 0
two O 0
isoproterenol B-Chemical 0
treated O 0
groups O 0
for O 0
severity O 0
of O 0
the O 0
induced O 0
lesions O 0
, O 0
changes O 0
in O 0
heart O 0
weight O 0
, O 0
or O 0
heart O 0
weight O 0
to O 0
body O 0
weight O 0
ratios O 0
. O 0

The O 0
results O 0
indicated O 0
that O 0
exercise O 0
reduced O 0
the O 0
mortality O 0
associated O 0
with O 0
the O 0
effects O 0
of O 0
large O 0
dosages O 0
of O 0
isoproterenol B-Chemical 0
but O 0
had O 0
little O 0
on O 0
the O 0
severity O 0
of O 0
the O 0
infarction B-Disease 0
. O 0

Human O 0
corticotropin B-Chemical 0
- O 0
releasing O 0
hormone O 0
and O 0
thyrotropin B-Chemical 0
- O 0
releasing O 0
hormone O 0
modulate O 0
the O 0
hypercapnic B-Disease 0
ventilatory O 0
response O 0
in O 0
humans O 0
. O 0

Human O 0
corticotropin B-Chemical 0
- O 0
releasing O 0
hormone O 0
( O 0
hCRH O 0
) O 0
and O 0
thyrotropin B-Chemical 0
- O 0
releasing O 0
hormone O 0
( O 0
TRH O 0
) O 0
are O 0
known O 0
to O 0
stimulate O 0
ventilation O 0
after O 0
i O 0
. O 0
v O 0
. O 0
administration O 0
in O 0
humans O 0
. O 0

In O 0
a O 0
placebo O 0
- O 0
controlled O 0
, O 0
single O 0
- O 0
blind O 0
study O 0
we O 0
aimed O 0
to O 0
clarify O 0
if O 0
both O 0
peptides O 0
act O 0
by O 0
altering O 0
central O 0
chemosensitivity O 0
. O 0

Two O 0
subsequent O 0
CO2 B-Chemical 0
- O 0
rebreathing O 0
tests O 0
were O 0
performed O 0
in O 0
healthy O 0
young O 0
volunteers O 0
. O 0

During O 0
the O 0
first O 0
test O 0
0 O 0
. O 0
9 O 0
% O 0
NaCl B-Chemical 0
was O 0
given O 0
i O 0
. O 0
v O 0
. O 0
; O 0
during O 0
the O 0
second O 0
test O 0
200 O 0
micrograms O 0
of O 0
hCRH O 0
( O 0
n O 0
= O 0
12 O 0
) O 0
or O 0
400 O 0
micrograms O 0
of O 0
TRH O 0
( O 0
n O 0
= O 0
6 O 0
) O 0
was O 0
administered O 0
i O 0
. O 0
v O 0
. O 0
Nine O 0
subjects O 0
received O 0
0 O 0
. O 0
9 O 0
% O 0
NaCl B-Chemical 0
i O 0
. O 0
v O 0
. O 0
during O 0
both O 0
rebreathing O 0
manoeuvres O 0
. O 0

The O 0
CO2 B-Chemical 0
- O 0
response O 0
curves O 0
for O 0
the O 0
two O 0
tests O 0
were O 0
compared O 0
within O 0
the O 0
same O 0
subject O 0
. O 0

In O 0
the O 0
hCRH O 0
group O 0
a O 0
marked O 0
parallel O 0
shift O 0
of O 0
the O 0
CO2 B-Chemical 0
- O 0
response O 0
curve O 0
to O 0
the O 0
left O 0
was O 0
observed O 0
after O 0
hCRH O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

The O 0
same O 0
effect O 0
occurred O 0
following O 0
TRH O 0
but O 0
was O 0
less O 0
striking O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

hCRH O 0
and O 0
TRH O 0
caused O 0
a O 0
reduction O 0
in O 0
the O 0
CO2 B-Chemical 0
threshold O 0
. O 0

The O 0
CO2 B-Chemical 0
- O 0
response O 0
curves O 0
in O 0
the O 0
control O 0
group O 0
were O 0
nearly O 0
identical O 0
. O 0

The O 0
results O 0
indicate O 0
an O 0
additive O 0
effect O 0
of O 0
both O 0
releasing O 0
hormones O 0
on O 0
the O 0
hypercapnic B-Disease 0
ventilatory O 0
response O 0
in O 0
humans O 0
, O 0
presumably O 0
independent O 0
of O 0
central O 0
chemosensitivity O 0
. O 0

Lamivudine B-Chemical 0
is O 0
effective O 0
in O 0
suppressing O 0
hepatitis B-Disease 0
B I-Disease 0
virus O 0
DNA O 0
in O 0
Chinese O 0
hepatitis B-Chemical 0
B I-Chemical 0
surface I-Chemical 0
antigen I-Chemical 0
carriers O 0
: O 0
a O 0
placebo O 0
- O 0
controlled O 0
trial O 0
. O 0

Lamivudine B-Chemical 0
is O 0
a O 0
novel O 0
2 B-Chemical 0
' I-Chemical 0
, I-Chemical 0
3 I-Chemical 0
' I-Chemical 0
- I-Chemical 0
dideoxy I-Chemical 0
cytosine I-Chemical 0
analogue O 0
that O 0
has O 0
potent O 0
inhibitory O 0
effects O 0
on O 0
hepatitis B-Disease 0
B I-Disease 0
virus O 0
replication O 0
in O 0
vitro O 0
and O 0
in O 0
vivo O 0
. O 0

We O 0
performed O 0
a O 0
single O 0
- O 0
blind O 0
, O 0
placebo O 0
- O 0
controlled O 0
study O 0
to O 0
assess O 0
its O 0
effectiveness O 0
and O 0
safety O 0
in O 0
Chinese O 0
hepatitis B-Chemical 0
B I-Chemical 0
surface I-Chemical 0
antigen I-Chemical 0
( O 0
HBsAg B-Chemical 0
) O 0
carriers O 0
. O 0

Forty O 0
- O 0
two O 0
Chinese O 0
HBsAg B-Chemical 0
carriers O 0
were O 0
randomized O 0
to O 0
receive O 0
placebo O 0
( O 0
6 O 0
patients O 0
) O 0
or O 0
lamivudine B-Chemical 0
orally O 0
in O 0
dosages O 0
of O 0
25 O 0
mg O 0
, O 0
100 O 0
mg O 0
, O 0
or O 0
300 O 0
mg O 0
daily O 0
( O 0
12 O 0
patients O 0
for O 0
each O 0
dosage O 0
) O 0
. O 0

The O 0
drug O 0
was O 0
given O 0
for O 0
4 O 0
weeks O 0
. O 0

The O 0
patients O 0
were O 0
closely O 0
monitored O 0
clinically O 0
, O 0
biochemically O 0
, O 0
and O 0
serologically O 0
up O 0
to O 0
4 O 0
weeks O 0
after O 0
drug O 0
treatment O 0
. O 0

All O 0
36 O 0
patients O 0
receiving O 0
lamivudine B-Chemical 0
had O 0
a O 0
decrease O 0
in O 0
hepatitis B-Disease 0
B I-Disease 0
virus O 0
( O 0
HBV O 0
) O 0
DNA O 0
values O 0
of O 0
> O 0
90 O 0
% O 0
( O 0
P O 0
< O 0
. O 0
001 O 0
compared O 0
with O 0
placebo O 0
) O 0
. O 0

Although O 0
25 O 0
mg O 0
of O 0
lamivudine B-Chemical 0
was O 0
slightly O 0
less O 0
effective O 0
than O 0
100 O 0
mg O 0
( O 0
P O 0
= O 0
. O 0
011 O 0
) O 0
and O 0
300 O 0
mg O 0
( O 0
P O 0
= O 0
. O 0
005 O 0
) O 0
, O 0
it O 0
still O 0
induced O 0
94 O 0
% O 0
suppression O 0
of O 0
HBV O 0
DNA O 0
after O 0
the O 0
fourth O 0
week O 0
of O 0
therapy O 0
. O 0

HBV O 0
DNA O 0
values O 0
returned O 0
to O 0
pretreatment O 0
levels O 0
within O 0
4 O 0
weeks O 0
of O 0
cessation O 0
of O 0
therapy O 0
. O 0

There O 0
was O 0
no O 0
change O 0
in O 0
the O 0
hepatitis B-Disease 0
B I-Disease 0
e O 0
antigen O 0
status O 0
or O 0
in O 0
aminotransferase O 0
levels O 0
. O 0

No O 0
serious O 0
adverse O 0
events O 0
were O 0
observed O 0
. O 0

In O 0
conclusion O 0
, O 0
a O 0
4 O 0
- O 0
week O 0
course O 0
of O 0
lamivudine B-Chemical 0
was O 0
safe O 0
and O 0
effective O 0
in O 0
suppression O 0
of O 0
HBV O 0
DNA O 0
in O 0
Chinese O 0
HBsAg B-Chemical 0
carriers O 0
. O 0

The O 0
suppression O 0
was O 0
> O 0
90 O 0
% O 0
but O 0
reversible O 0
. O 0

Studies O 0
with O 0
long O 0
- O 0
term O 0
lamivudine B-Chemical 0
administration O 0
should O 0
be O 0
performed O 0
to O 0
determine O 0
if O 0
prolonged O 0
suppression O 0
of O 0
HBV O 0
DNA O 0
can O 0
be O 0
achieved O 0
. O 0

Population O 0
- O 0
based O 0
study O 0
of O 0
risk O 0
of O 0
venous B-Disease 0
thromboembolism I-Disease 0
associated O 0
with O 0
various O 0
oral B-Chemical 0
contraceptives I-Chemical 0
. O 0

BACKGROUND O 0
: O 0
Four O 0
studies O 0
published O 0
since O 0
December O 0
, O 0
1995 O 0
, O 0
reported O 0
that O 0
the O 0
incidence O 0
of O 0
venous B-Disease 0
thromboembolism I-Disease 0
( O 0
VTE B-Disease 0
) O 0
was O 0
higher O 0
in O 0
women O 0
who O 0
used O 0
oral B-Chemical 0
contraceptives I-Chemical 0
( O 0
OCs B-Chemical 0
) O 0
containing O 0
the O 0
third O 0
- O 0
generation O 0
progestagens B-Chemical 0
gestodene B-Chemical 0
or O 0
desogestrel B-Chemical 0
than O 0
in O 0
users O 0
of O 0
OCs B-Chemical 0
containing O 0
second O 0
- O 0
generation O 0
progestagens B-Chemical 0
. O 0

However O 0
, O 0
confounding O 0
and O 0
bias O 0
in O 0
the O 0
design O 0
of O 0
these O 0
studies O 0
may O 0
have O 0
affected O 0
the O 0
findings O 0
. O 0

The O 0
aim O 0
of O 0
our O 0
study O 0
was O 0
to O 0
re O 0
- O 0
examine O 0
the O 0
association O 0
between O 0
risk O 0
of O 0
VTE B-Disease 0
and O 0
OC B-Chemical 0
use O 0
with O 0
a O 0
different O 0
study O 0
design O 0
and O 0
analysis O 0
to O 0
avoid O 0
some O 0
of O 0
the O 0
bias O 0
and O 0
confounding O 0
of O 0
the O 0
earlier O 0
studies O 0
. O 0

METHODS O 0
: O 0
We O 0
used O 0
computer O 0
records O 0
of O 0
patients O 0
from O 0
143 O 0
general O 0
practices O 0
in O 0
the O 0
UK O 0
. O 0

The O 0
study O 0
was O 0
based O 0
on O 0
the O 0
medical O 0
records O 0
of O 0
about O 0
540 O 0
, O 0
000 O 0
women O 0
born O 0
between O 0
1941 O 0
and O 0
1981 O 0
. O 0

All O 0
women O 0
who O 0
had O 0
a O 0
recorded O 0
diagnosis O 0
of O 0
deep B-Disease 0
- I-Disease 0
vein I-Disease 0
thrombosis I-Disease 0
, O 0
venous B-Disease 0
thrombosis I-Disease 0
not O 0
otherwise O 0
specified O 0
, O 0
or O 0
pulmonary O 0
embolus O 0
during O 0
the O 0
study O 0
period O 0
, O 0
and O 0
who O 0
had O 0
been O 0
treated O 0
with O 0
an O 0
anticoagulant O 0
were O 0
identified O 0
as O 0
potential O 0
cases O 0
of O 0
VTE B-Disease 0
. O 0

We O 0
did O 0
a O 0
cohort O 0
analysis O 0
to O 0
estimate O 0
and O 0
compare O 0
incidence O 0
of O 0
VTE B-Disease 0
in O 0
users O 0
of O 0
the O 0
main O 0
OC B-Chemical 0
preparations O 0
, O 0
and O 0
a O 0
nested O 0
case O 0
- O 0
control O 0
study O 0
to O 0
calculate O 0
the O 0
odds O 0
ratios O 0
of O 0
VTE B-Disease 0
associated O 0
with O 0
use O 0
of O 0
different O 0
types O 0
of O 0
OC B-Chemical 0
, O 0
after O 0
adjustment O 0
for O 0
potential O 0
confounding O 0
factors O 0
. O 0

In O 0
the O 0
case O 0
- O 0
control O 0
study O 0
, O 0
we O 0
matched O 0
cases O 0
to O 0
controls O 0
by O 0
exact O 0
year O 0
of O 0
birth O 0
, O 0
practice O 0
, O 0
and O 0
current O 0
use O 0
of O 0
OCs B-Chemical 0
. O 0

We O 0
used O 0
a O 0
multiple O 0
logistic O 0
regression O 0
model O 0
that O 0
included O 0
body O 0
- O 0
mass O 0
index O 0
, O 0
number O 0
of O 0
cycles O 0
, O 0
change O 0
in O 0
type O 0
of O 0
OC B-Chemical 0
prescribed O 0
within O 0
3 O 0
months O 0
of O 0
the O 0
event O 0
, O 0
previous O 0
pregnancy O 0
, O 0
and O 0
concurrent O 0
disease O 0
. O 0

FINDINGS O 0
: O 0
85 O 0
women O 0
met O 0
the O 0
inclusion O 0
criteria O 0
for O 0
VTE B-Disease 0
, O 0
two O 0
of O 0
whom O 0
were O 0
users O 0
of O 0
progestagen B-Chemical 0
- O 0
only O 0
OCs B-Chemical 0
. O 0

Of O 0
the O 0
83 O 0
cases O 0
of O 0
VTE B-Disease 0
associated O 0
with O 0
use O 0
of O 0
combined O 0
OCs B-Chemical 0
, O 0
43 O 0
were O 0
recorded O 0
as O 0
deep B-Disease 0
- I-Disease 0
vein I-Disease 0
thrombosis I-Disease 0
, O 0
35 O 0
as O 0
pulmonary O 0
thrombosis B-Disease 0
, O 0
and O 0
five O 0
as O 0
venous B-Disease 0
thrombosis I-Disease 0
not O 0
otherwise O 0
specified O 0
. O 0

The O 0
crude O 0
rate O 0
of O 0
VTE B-Disease 0
per O 0
10 O 0
, O 0
000 O 0
woman O 0
- O 0
years O 0
was O 0
4 O 0
. O 0
10 O 0
in O 0
current O 0
users O 0
of O 0
any O 0
OC B-Chemical 0
, O 0
3 O 0
. O 0
10 O 0
in O 0
users O 0
of O 0
second O 0
- O 0
generation O 0
OCs B-Chemical 0
, O 0
and O 0
4 O 0
. O 0
96 O 0
in O 0
users O 0
of O 0
third O 0
- O 0
generation O 0
preparations O 0
. O 0

After O 0
adjustment O 0
for O 0
age O 0
, O 0
the O 0
rate O 0
ratio O 0
of O 0
VTE B-Disease 0
in O 0
users O 0
of O 0
third O 0
- O 0
generation O 0
relative O 0
to O 0
second O 0
- O 0
generation O 0
OCs B-Chemical 0
was O 0
1 O 0
. O 0
68 O 0
( O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
04 O 0
- O 0
2 O 0
. O 0
75 O 0
) O 0
. O 0

Logistic O 0
regression O 0
showed O 0
no O 0
significant O 0
difference O 0
in O 0
the O 0
risk O 0
of O 0
VTE B-Disease 0
between O 0
users O 0
of O 0
third O 0
- O 0
generation O 0
and O 0
second O 0
- O 0
generation O 0
OCs B-Chemical 0
. O 0

Among O 0
users O 0
of O 0
third O 0
- O 0
generation O 0
progestagens B-Chemical 0
, O 0
the O 0
risk O 0
of O 0
VTE B-Disease 0
was O 0
higher O 0
in O 0
users O 0
of O 0
desogestrel B-Chemical 0
with O 0
20 O 0
g O 0
ethinyloestradiol B-Chemical 0
than O 0
in O 0
users O 0
of O 0
gestodene B-Chemical 0
or O 0
desogestrel B-Chemical 0
with O 0
30 O 0
g O 0
ethinyloestradiol B-Chemical 0
. O 0

With O 0
all O 0
second O 0
- O 0
generation O 0
OCs B-Chemical 0
as O 0
the O 0
reference O 0
, O 0
the O 0
odds O 0
ratios O 0
for O 0
VTE B-Disease 0
were O 0
3 O 0
. O 0
49 O 0
( O 0
1 O 0
. O 0
21 O 0
- O 0
10 O 0
. O 0
12 O 0
) O 0
for O 0
desogestrel B-Chemical 0
plus O 0
20 O 0
g O 0
ethinyloestradiol B-Chemical 0
and O 0
1 O 0
. O 0
18 O 0
( O 0
0 O 0
. O 0
66 O 0
- O 0
2 O 0
. O 0
17 O 0
) O 0
for O 0
the O 0
other O 0
third O 0
- O 0
generation O 0
progestagens B-Chemical 0
. O 0

INTERPRETATION O 0
: O 0
The O 0
previously O 0
reported O 0
increase O 0
in O 0
odds O 0
ratio O 0
associated O 0
with O 0
third O 0
- O 0
generation O 0
OCs B-Chemical 0
when O 0
compared O 0
with O 0
second O 0
- O 0
generation O 0
products O 0
is O 0
likely O 0
to O 0
have O 0
been O 0
the O 0
result O 0
of O 0
residual O 0
confounding O 0
by O 0
age O 0
. O 0

The O 0
increased O 0
odds O 0
ratio O 0
associated O 0
with O 0
products O 0
containing O 0
20 O 0
micrograms O 0
ethinyloestradiol B-Chemical 0
and O 0
desogestrel B-Chemical 0
compared O 0
with O 0
the O 0
30 O 0
micrograms O 0
product O 0
is O 0
biologically O 0
implausible O 0
, O 0
and O 0
is O 0
likely O 0
to O 0
be O 0
the O 0
result O 0
of O 0
preferential O 0
prescribing O 0
and O 0
, O 0
thus O 0
, O 0
confounding O 0
. O 0

MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
augments O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
electrographic O 0
seizure B-Disease 0
but O 0
protects O 0
against O 0
brain B-Disease 0
damage I-Disease 0
in O 0
rats O 0
. O 0

1 O 0
. O 0

The O 0
authors O 0
examined O 0
the O 0
anticonvulsant O 0
effects O 0
of O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
on O 0
the O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizure B-Disease 0
model O 0
. O 0

Intraperitoneal O 0
injection O 0
of O 0
pilocarpine B-Chemical 0
( O 0
400 O 0
mg O 0
/ O 0
kg O 0
) O 0
induced O 0
tonic B-Disease 0
and I-Disease 0
clonic I-Disease 0
seizure I-Disease 0
. O 0

Scopolamine B-Chemical 0
( O 0
10 O 0
mg O 0
/ O 0
kg O 0
) O 0
and O 0
pentobarbital B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
prevented O 0
development O 0
of O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
behavioral O 0
seizure B-Disease 0
but O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
( O 0
0 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
did O 0
not O 0
. O 0

2 O 0
. O 0

An O 0
electrical O 0
seizure B-Disease 0
measured O 0
with O 0
hippocampal O 0
EEG O 0
appeared O 0
in O 0
the O 0
pilocarpine B-Chemical 0
- O 0
treated O 0
group O 0
. O 0

Scopolamine B-Chemical 0
and O 0
pentobarbital B-Chemical 0
blocked O 0
the O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
electrographic O 0
seizure B-Disease 0
, O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
treatment O 0
augmented O 0
the O 0
electrographic O 0
seizure B-Disease 0
induced O 0
by O 0
pilocarpine B-Chemical 0
. O 0

3 O 0
. O 0

Brain B-Disease 0
damage I-Disease 0
was O 0
assessed O 0
by O 0
examining O 0
the O 0
hippocampus O 0
microscopically O 0
. O 0

Pilocarpine B-Chemical 0
produced O 0
neuronal B-Disease 0
death I-Disease 0
in O 0
the O 0
hippocampus O 0
, O 0
which O 0
showed O 0
pyknotic O 0
changes O 0
. O 0

Pentobarbital B-Chemical 0
, O 0
scopolamine B-Chemical 0
and O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
protected O 0
the O 0
brain B-Disease 0
damage I-Disease 0
by O 0
pilocarpine B-Chemical 0
, O 0
though O 0
in O 0
the O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
- O 0
treated O 0
group O 0
, O 0
the O 0
pyramidal O 0
cells O 0
of O 0
hippocampus O 0
appeared O 0
darker O 0
than O 0
normal O 0
. O 0

In O 0
all O 0
treatments O 0
, O 0
granule O 0
cells O 0
of O 0
the O 0
dentate O 0
gyrus O 0
were O 0
not O 0
affected O 0
. O 0

4 O 0
. O 0

These O 0
results O 0
indicate O 0
that O 0
status B-Disease 0
epilepticus I-Disease 0
induced O 0
by O 0
pilocarpine B-Chemical 0
is O 0
initiated O 0
by O 0
cholinergic O 0
overstimulation O 0
and O 0
propagated O 0
by O 0
glutamatergic O 0
transmission O 0
, O 0
the O 0
elevation O 0
of O 0
which O 0
may O 0
cause O 0
brain B-Disease 0
damage I-Disease 0
through O 0
an O 0
excitatory O 0
NMDA B-Chemical 0
receptor O 0
- O 0
mediated O 0
mechanism O 0
. O 0

Paclitaxel B-Chemical 0
, O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
, O 0
and O 0
folinic B-Chemical 0
acid I-Chemical 0
in O 0
metastatic O 0
breast B-Disease 0
cancer I-Disease 0
: O 0
BRE O 0
- O 0
26 O 0
, O 0
a O 0
phase O 0
II O 0
trial O 0
. O 0

5 B-Chemical 0
- I-Chemical 0
Fluorouracil I-Chemical 0
plus O 0
folinic B-Chemical 0
acid I-Chemical 0
and O 0
paclitaxel B-Chemical 0
( O 0
Taxol B-Chemical 0
; O 0
Bristol O 0
- O 0
Myers O 0
Squibb O 0
Company O 0
, O 0
Princeton O 0
, O 0
NJ O 0
) O 0
are O 0
effective O 0
salvage O 0
therapies O 0
for O 0
metastatic O 0
breast B-Disease 0
cancer I-Disease 0
patients O 0
. O 0

Paclitaxel B-Chemical 0
and O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
have O 0
additive O 0
cytotoxicity B-Disease 0
in O 0
MCF O 0
- O 0
7 O 0
cell O 0
lines O 0
. O 0

We O 0
performed O 0
a O 0
phase O 0
II O 0
trial O 0
of O 0
paclitaxel B-Chemical 0
175 O 0
mg O 0
/ O 0
m2 O 0
over O 0
3 O 0
hours O 0
on O 0
day O 0
I O 0
followed O 0
by O 0
folinic B-Chemical 0
acid I-Chemical 0
300 O 0
mg O 0
over O 0
1 O 0
hour O 0
before O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
350 O 0
mg O 0
/ O 0
m2 O 0
on O 0
days O 0
1 O 0
to O 0
3 O 0
every O 0
28 O 0
days O 0
( O 0
TFL O 0
) O 0
in O 0
women O 0
with O 0
metastatic O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

Analysis O 0
is O 0
reported O 0
on O 0
37 O 0
patients O 0
with O 0
a O 0
minimum O 0
of O 0
6 O 0
months O 0
follow O 0
- O 0
up O 0
who O 0
received O 0
a O 0
total O 0
of O 0
192 O 0
cycles O 0
of O 0
TFL O 0
: O 0
nine O 0
cycles O 0
( O 0
5 O 0
% O 0
) O 0
were O 0
associated O 0
with O 0
grade O 0
3 O 0
/ O 0
4 O 0
neutropenia B-Disease 0
requiring O 0
hospitalization O 0
; O 0
seven O 0
( O 0
4 O 0
% O 0
) O 0
cycles O 0
in O 0
two O 0
patients O 0
required O 0
granulocyte B-Chemical 0
colony I-Chemical 0
- I-Chemical 0
stimulating I-Chemical 0
factor I-Chemical 0
due O 0
to O 0
neutropenia B-Disease 0
; O 0
no O 0
patient O 0
required O 0
platelet O 0
transfusions O 0
. O 0

Grade O 0
3 O 0
/ O 0
4 O 0
nonhematologic O 0
toxicities B-Disease 0
were O 0
uncommon O 0
. O 0

Among O 0
the O 0
34 O 0
patients O 0
evaluable O 0
for O 0
response O 0
, O 0
there O 0
were O 0
three O 0
complete O 0
responses O 0
( O 0
9 O 0
% O 0
) O 0
and O 0
18 O 0
partial O 0
responses O 0
( O 0
53 O 0
% O 0
) O 0
for O 0
an O 0
overall O 0
response O 0
rate O 0
of O 0
62 O 0
% O 0
. O 0

Of O 0
the O 0
19 O 0
evaluable O 0
patients O 0
with O 0
prior O 0
doxorubicin B-Chemical 0
exposure O 0
, O 0
11 O 0
( O 0
58 O 0
% O 0
) O 0
responded O 0
compared O 0
with O 0
nine O 0
of O 0
15 O 0
( O 0
60 O 0
% O 0
) O 0
without O 0
prior O 0
doxorubicin B-Chemical 0
. O 0

Plasma O 0
paclitaxel B-Chemical 0
concentrations O 0
were O 0
measured O 0
at O 0
the O 0
completion O 0
of O 0
paclitaxel B-Chemical 0
infusion O 0
and O 0
at O 0
24 O 0
hours O 0
in O 0
19 O 0
patients O 0
. O 0

TFL O 0
is O 0
an O 0
active O 0
, O 0
well O 0
- O 0
tolerated O 0
regimen O 0
in O 0
metastatic O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

Efficacy O 0
and O 0
proarrhythmia B-Disease 0
with O 0
the O 0
use O 0
of O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
for O 0
sustained O 0
ventricular B-Disease 0
tachyarrhythmias I-Disease 0
. O 0

This O 0
study O 0
prospectively O 0
evaluated O 0
the O 0
clinical O 0
efficacy O 0
, O 0
the O 0
incidence O 0
of O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
, O 0
and O 0
the O 0
presumable O 0
risk O 0
factors O 0
for O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
in O 0
patients O 0
treated O 0
with O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
for O 0
sustained O 0
ventricular B-Disease 0
tachyarrhythmias I-Disease 0
. O 0

Eighty O 0
- O 0
one O 0
consecutive O 0
patients O 0
( O 0
54 O 0
with O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
, O 0
and O 0
20 O 0
with O 0
dilated B-Disease 0
cardiomyopathy I-Disease 0
) O 0
with O 0
inducible O 0
sustained O 0
ventricular B-Disease 0
tachycardia I-Disease 0
or O 0
ventricular B-Disease 0
fibrillation I-Disease 0
received O 0
oral O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
to O 0
prevent O 0
induction O 0
of O 0
the O 0
ventricular B-Disease 0
tachyarrhythmia I-Disease 0
. O 0

During O 0
oral O 0
loading O 0
with O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
, O 0
continuous O 0
electrocardiographic O 0
( O 0
ECG O 0
) O 0
monitoring O 0
was O 0
performed O 0
. O 0

Those O 0
patients O 0
in O 0
whom O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
prevented O 0
induction O 0
of O 0
ventricular B-Disease 0
tachycardia I-Disease 0
or O 0
ventricular B-Disease 0
fibrillation I-Disease 0
were O 0
discharged O 0
with O 0
the O 0
drug O 0
and O 0
followed O 0
up O 0
on O 0
an O 0
outpatient O 0
basis O 0
for O 0
21 O 0
+ O 0
/ O 0
- O 0
18 O 0
months O 0
. O 0

Induction O 0
of O 0
the O 0
ventricular B-Disease 0
tachyarrhythmia I-Disease 0
was O 0
prevented O 0
by O 0
oral O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
in O 0
35 O 0
( O 0
43 O 0
% O 0
) O 0
patients O 0
; O 0
the O 0
ventricular B-Disease 0
tachyarrhythmia I-Disease 0
remained O 0
inducible O 0
in O 0
40 O 0
( O 0
49 O 0
% O 0
) O 0
patients O 0
; O 0
and O 0
two O 0
( O 0
2 O 0
. O 0
5 O 0
% O 0
) O 0
patients O 0
did O 0
not O 0
tolerate O 0
even O 0
40 O 0
mg O 0
of O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
once O 0
daily O 0
. O 0

Four O 0
( O 0
5 O 0
% O 0
) O 0
patients O 0
had O 0
from O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
during O 0
the O 0
initial O 0
oral O 0
treatment O 0
with O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
. O 0

Neither O 0
ECG O 0
[ O 0
sinus O 0
- O 0
cycle O 0
length O 0
( O 0
SCL O 0
) O 0
, O 0
QT O 0
or O 0
QTc O 0
interval O 0
, O 0
or O 0
U O 0
wave O 0
] O 0
nor O 0
clinical O 0
parameters O 0
identified O 0
patients O 0
at O 0
risk O 0
for O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
. O 0

However O 0
, O 0
the O 0
oral O 0
dose O 0
of O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
was O 0
significantly O 0
lower O 0
in O 0
patients O 0
with O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
( O 0
200 O 0
+ O 0
/ O 0
- O 0
46 O 0
vs O 0
. O 0
328 O 0
+ O 0
/ O 0
- O 0
53 O 0
mg O 0
/ O 0
day O 0
; O 0
p O 0
= O 0
0 O 0
. O 0
0017 O 0
) O 0
. O 0

Risk O 0
factors O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
were O 0
the O 0
appearance O 0
of O 0
an O 0
U O 0
wave O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
049 O 0
) O 0
, O 0
female O 0
gender O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
015 O 0
) O 0
, O 0
and O 0
significant O 0
dose O 0
- O 0
corrected O 0
changes O 0
of O 0
SCL O 0
, O 0
QT O 0
interval O 0
, O 0
and O 0
QTc O 0
interval O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

During O 0
follow O 0
- O 0
up O 0
, O 0
seven O 0
( O 0
20 O 0
% O 0
) O 0
patients O 0
had O 0
a O 0
nonfatal O 0
ventricular B-Disease 0
tachycardia I-Disease 0
recurrence O 0
, O 0
and O 0
two O 0
( O 0
6 O 0
% O 0
) O 0
patients O 0
died O 0
suddenly O 0
. O 0

One O 0
female O 0
patient O 0
with O 0
stable O 0
cardiac B-Disease 0
disease I-Disease 0
had O 0
recurrent O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
after O 0
2 O 0
years O 0
of O 0
successful O 0
treatment O 0
with O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
. O 0

Torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
occurred O 0
early O 0
during O 0
treatment O 0
even O 0
with O 0
low O 0
doses O 0
of O 0
oral O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
. O 0

Pronounced O 0
changes O 0
in O 0
the O 0
surface O 0
ECG O 0
( O 0
cycle O 0
length O 0
, O 0
QT O 0
, O 0
and O 0
QTc O 0
) O 0
in O 0
relation O 0
to O 0
the O 0
dose O 0
of O 0
oral O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
might O 0
identify O 0
a O 0
subgroup O 0
of O 0
patients O 0
with O 0
an O 0
increased O 0
risk O 0
for O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
. O 0

Other O 0
ECG O 0
parameters O 0
before O 0
the O 0
application O 0
of O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
did O 0
not O 0
identify O 0
patients O 0
at O 0
increased O 0
risk O 0
for O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
. O 0

Recurrence O 0
rates O 0
of O 0
ventricular B-Disease 0
tachyarrhythmias I-Disease 0
are O 0
high O 0
despite O 0
complete O 0
suppression O 0
of O 0
the O 0
arrhythmia B-Disease 0
during O 0
programmed O 0
stimulation O 0
. O 0

Therefore O 0
programmed O 0
electrical O 0
stimulation O 0
in O 0
the O 0
case O 0
of O 0
d B-Chemical 0
, I-Chemical 0
l I-Chemical 0
- I-Chemical 0
sotalol I-Chemical 0
seems O 0
to O 0
be O 0
of O 0
limited O 0
prognostic O 0
value O 0
. O 0

Chronic O 0
hyperprolactinemia B-Disease 0
and O 0
changes O 0
in O 0
dopamine B-Chemical 0
neurons O 0
. O 0

The O 0
tuberoinfundibular O 0
dopaminergic O 0
( O 0
TIDA O 0
) O 0
system O 0
is O 0
known O 0
to O 0
inhibit O 0
prolactin O 0
( O 0
PRL O 0
) O 0
secretion O 0
. O 0

In O 0
young O 0
animals O 0
this O 0
system O 0
responds O 0
to O 0
acute O 0
elevations O 0
in O 0
serum O 0
PRL O 0
by O 0
increasing O 0
its O 0
activity O 0
. O 0

However O 0
, O 0
this O 0
responsiveness O 0
is O 0
lost O 0
in O 0
aging O 0
rats O 0
with O 0
chronically O 0
high O 0
serum O 0
PRL O 0
levels O 0
. O 0

The O 0
purpose O 0
of O 0
this O 0
study O 0
was O 0
to O 0
induce O 0
hyperprolactinemia B-Disease 0
in O 0
rats O 0
for O 0
extended O 0
periods O 0
of O 0
time O 0
and O 0
examine O 0
its O 0
effects O 0
on O 0
dopaminergic O 0
systems O 0
in O 0
the O 0
brain O 0
. O 0

Hyperprolactinemia B-Disease 0
was O 0
induced O 0
by O 0
treatment O 0
with O 0
haloperidol B-Chemical 0
, O 0
a O 0
dopamine B-Chemical 0
receptor O 0
antagonist O 0
, O 0
and O 0
Palkovits O 0
' O 0
microdissection O 0
technique O 0
in O 0
combination O 0
with O 0
high O 0
- O 0
performance O 0
liquid O 0
chromatography O 0
was O 0
used O 0
to O 0
measure O 0
neurotransmitter O 0
concentrations O 0
in O 0
several O 0
areas O 0
of O 0
the O 0
brain O 0
. O 0

After O 0
6 O 0
months O 0
of O 0
hyperprolactinemia B-Disease 0
, O 0
dopamine B-Chemical 0
( O 0
DA B-Chemical 0
) O 0
concentrations O 0
in O 0
the O 0
median O 0
eminence O 0
( O 0
ME O 0
) O 0
increased O 0
by O 0
84 O 0
% O 0
over O 0
the O 0
control O 0
group O 0
. O 0

Nine O 0
months O 0
of O 0
hyperprolactinemia B-Disease 0
produced O 0
a O 0
50 O 0
% O 0
increase O 0
in O 0
DA B-Chemical 0
concentrations O 0
in O 0
the O 0
ME O 0
over O 0
the O 0
control O 0
group O 0
. O 0

However O 0
, O 0
DA B-Chemical 0
response O 0
was O 0
lost O 0
if O 0
a O 0
9 O 0
- O 0
month O 0
long O 0
haloperidol B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
was O 0
followed O 0
by O 0
a O 0
1 O 0
1 O 0
/ O 0
2 O 0
month O 0
- O 0
long O 0
extremely O 0
high O 0
increase O 0
in O 0
serum O 0
PRL O 0
levels O 0
produced O 0
by O 0
implantation O 0
of O 0
MMQ O 0
cells O 0
under O 0
the O 0
kidney O 0
capsule O 0
. O 0

There O 0
was O 0
no O 0
change O 0
in O 0
the O 0
levels O 0
of O 0
DA B-Chemical 0
, O 0
norepinephrine B-Chemical 0
( O 0
NE B-Chemical 0
) O 0
, O 0
serotonin B-Chemical 0
( O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
) O 0
, O 0
or O 0
their O 0
metabolites O 0
in O 0
the O 0
arcuate O 0
nucleus O 0
( O 0
AN O 0
) O 0
, O 0
medial O 0
preoptic O 0
area O 0
( O 0
MPA O 0
) O 0
, O 0
caudate O 0
putamen O 0
( O 0
CP O 0
) O 0
, O 0
substantia O 0
nigra O 0
( O 0
SN O 0
) O 0
, O 0
and O 0
zona O 0
incerta O 0
( O 0
ZI O 0
) O 0
, O 0
except O 0
for O 0
a O 0
decrease O 0
in O 0
5 B-Chemical 0
- I-Chemical 0
hydroxyindoleacetic I-Chemical 0
acid I-Chemical 0
( O 0
5 B-Chemical 0
- I-Chemical 0
HIAA I-Chemical 0
) O 0
in O 0
the O 0
AN O 0
after O 0
6 O 0
- O 0
months O 0
of O 0
hyperprolactinemia B-Disease 0
and O 0
an O 0
increase O 0
in O 0
DA B-Chemical 0
concentrations O 0
in O 0
the O 0
AN O 0
after O 0
9 O 0
- O 0
months O 0
of O 0
hyperprolactinemia B-Disease 0
. O 0

These O 0
results O 0
demonstrate O 0
that O 0
hyperprolactinemia B-Disease 0
specifically O 0
affects O 0
TIDA O 0
neurons O 0
and O 0
these O 0
effects O 0
vary O 0
, O 0
depending O 0
on O 0
the O 0
duration O 0
and O 0
intensity O 0
of O 0
hyperprolactinemia B-Disease 0
. O 0

The O 0
age O 0
- O 0
related O 0
decrease O 0
in O 0
hypothalamic O 0
dopamine B-Chemical 0
function O 0
may O 0
be O 0
associated O 0
with O 0
increases O 0
in O 0
PRL O 0
secretion O 0
. O 0

Treatment O 0
- O 0
related O 0
disseminated O 0
necrotizing O 0
leukoencephalopathy B-Disease 0
with O 0
characteristic O 0
contrast O 0
enhancement O 0
of O 0
the O 0
white O 0
matter O 0
. O 0

This O 0
report O 0
describes O 0
unique O 0
contrast O 0
enhancement O 0
of O 0
the O 0
white O 0
matter O 0
on O 0
T1 O 0
- O 0
weighted O 0
magnetic O 0
resonance O 0
images O 0
of O 0
two O 0
patients O 0
with O 0
disseminated O 0
necrotizing O 0
leukoencephalopathy B-Disease 0
, O 0
which O 0
developed O 0
from O 0
acute B-Disease 0
lymphoblastic I-Disease 0
leukemia I-Disease 0
treated O 0
with O 0
high O 0
- O 0
dose O 0
methotrexate B-Chemical 0
. O 0

In O 0
both O 0
patients O 0
, O 0
the O 0
enhancement O 0
was O 0
more O 0
pronounced O 0
near O 0
the O 0
base O 0
of O 0
the O 0
brain O 0
than O 0
at O 0
the O 0
vertex O 0
. O 0

Necropsy O 0
of O 0
the O 0
first O 0
case O 0
revealed O 0
loss B-Disease 0
of I-Disease 0
myelination I-Disease 0
and O 0
necrosis B-Disease 0
of O 0
the O 0
white O 0
matter O 0
. O 0

Possible O 0
mechanisms O 0
causing O 0
such O 0
a O 0
leukoencephalopathy B-Disease 0
are O 0
discussed O 0
. O 0

Thrombotic B-Disease 0
complications O 0
in O 0
acute B-Disease 0
promyelocytic I-Disease 0
leukemia I-Disease 0
during O 0
all B-Chemical 0
- I-Chemical 0
trans I-Chemical 0
- I-Chemical 0
retinoic I-Chemical 0
acid I-Chemical 0
therapy O 0
. O 0

A O 0
case O 0
of O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
, O 0
due O 0
to O 0
occlusion B-Disease 0
of I-Disease 0
renal I-Disease 0
vessels I-Disease 0
in O 0
a O 0
patient O 0
with O 0
acute B-Disease 0
promyelocytic I-Disease 0
leukemia I-Disease 0
( O 0
APL B-Disease 0
) O 0
treated O 0
with O 0
all B-Chemical 0
- I-Chemical 0
trans I-Chemical 0
- I-Chemical 0
retinoic I-Chemical 0
acid I-Chemical 0
( O 0
ATRA B-Chemical 0
) O 0
and O 0
tranexamic B-Chemical 0
acid I-Chemical 0
has O 0
been O 0
described O 0
recently O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
in O 0
an O 0
APL B-Disease 0
patient O 0
treated O 0
with O 0
ATRA B-Chemical 0
alone O 0
. O 0

This O 0
case O 0
further O 0
supports O 0
the O 0
concern O 0
about O 0
thromboembolic B-Disease 0
complications O 0
associated O 0
with O 0
ATRA B-Chemical 0
therapy O 0
in O 0
APL B-Disease 0
patients O 0
. O 0

The O 0
patients O 0
, O 0
a O 0
43 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
, O 0
presented O 0
all O 0
the O 0
signs O 0
and O 0
symptoms O 0
of O 0
APL B-Disease 0
and O 0
was O 0
included O 0
in O 0
a O 0
treatment O 0
protocol O 0
with O 0
ATRA B-Chemical 0
. O 0

After O 0
10 O 0
days O 0
of O 0
treatment O 0
, O 0
he O 0
developed O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
that O 0
was O 0
completely O 0
reversible O 0
after O 0
complete O 0
remission O 0
of O 0
APL B-Disease 0
was O 0
achieved O 0
and O 0
therapy O 0
discontinued O 0
. O 0

We O 0
conclude O 0
that O 0
ATRA B-Chemical 0
is O 0
a O 0
valid O 0
therapeutic O 0
choice O 0
for O 0
patients O 0
with O 0
APL B-Disease 0
, O 0
although O 0
the O 0
procoagulant O 0
tendency O 0
is O 0
not O 0
completely O 0
corrected O 0
. O 0

Thrombotic B-Disease 0
events O 0
, O 0
however O 0
, O 0
could O 0
be O 0
avoided O 0
by O 0
using O 0
low O 0
- O 0
dose O 0
heparin B-Chemical 0
. O 0

Pupillary O 0
changes O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
stimulant O 0
- O 0
induced O 0
mania B-Disease 0
: O 0
a O 0
case O 0
report O 0
. O 0

A O 0
30 O 0
- O 0
year O 0
- O 0
old O 0
cocaine B-Chemical 0
- O 0
dependent O 0
man O 0
who O 0
was O 0
a O 0
subject O 0
in O 0
a O 0
study O 0
evaluating O 0
the O 0
anticraving O 0
efficacy O 0
of O 0
the O 0
stimulant O 0
medication O 0
diethylpropion B-Chemical 0
( O 0
DEP B-Chemical 0
) O 0
became O 0
manic B-Disease 0
during O 0
his O 0
second O 0
week O 0
on O 0
the O 0
study O 0
drug O 0
. O 0

Pupillometric O 0
changes O 0
while O 0
on O 0
DEP B-Chemical 0
, O 0
especially O 0
changes O 0
in O 0
the O 0
total O 0
power O 0
of O 0
pupillary B-Disease 0
oscillation I-Disease 0
, O 0
were O 0
dramatically O 0
different O 0
than O 0
those O 0
observed O 0
in O 0
the O 0
eight O 0
other O 0
study O 0
subjects O 0
who O 0
did O 0
not O 0
become O 0
manic B-Disease 0
. O 0

The O 0
large O 0
changes O 0
in O 0
total O 0
power O 0
of O 0
pupillary B-Disease 0
oscillation I-Disease 0
occurred O 0
a O 0
few O 0
days O 0
before O 0
the O 0
patient O 0
became O 0
fully O 0
manic B-Disease 0
. O 0

Such O 0
medication O 0
- O 0
associated O 0
changes O 0
in O 0
the O 0
total O 0
power O 0
of O 0
pupillary B-Disease 0
oscillation I-Disease 0
might O 0
be O 0
of O 0
utility O 0
in O 0
identifying O 0
persons O 0
at O 0
risk O 0
for O 0
manic B-Disease 0
- O 0
like O 0
adverse O 0
effects O 0
during O 0
the O 0
medical O 0
use O 0
of O 0
psychomotor O 0
stimulants O 0
or O 0
sympathomimetic O 0
agents O 0
. O 0

Fetal O 0
risks O 0
due O 0
to O 0
warfarin B-Chemical 0
therapy O 0
during O 0
pregnancy O 0
. O 0

Two O 0
mothers O 0
with O 0
heart O 0
valve O 0
prosthesis O 0
were O 0
treated O 0
with O 0
warfarin B-Chemical 0
during O 0
pregnancy O 0
. O 0

In O 0
the O 0
first O 0
case O 0
a O 0
caesarean O 0
section O 0
was O 0
done O 0
one O 0
week O 0
after O 0
replacement O 0
of O 0
warfarin B-Chemical 0
with O 0
heparin B-Chemical 0
. O 0

The O 0
baby O 0
died O 0
of O 0
cerebral B-Disease 0
and I-Disease 0
pulmonary I-Disease 0
hemorrhage I-Disease 0
. O 0

The O 0
second O 0
mother O 0
had O 0
a O 0
male O 0
infant O 0
by O 0
caesarean O 0
section O 0
. O 0

The O 0
baby O 0
showed O 0
warfarin B-Chemical 0
- O 0
induced O 0
embryopathy B-Disease 0
with O 0
nasal B-Disease 0
hypoplasia I-Disease 0
and O 0
stippled B-Disease 0
epiphyses I-Disease 0
( O 0
chondrodysplasia B-Disease 0
punctata I-Disease 0
) O 0
. O 0

Nasal B-Disease 0
hypoplasia I-Disease 0
with O 0
or O 0
without O 0
stippled B-Disease 0
epiphyses I-Disease 0
has O 0
now O 0
been O 0
reported O 0
in O 0
11 O 0
infants O 0
born O 0
to O 0
mothers O 0
treated O 0
with O 0
warfarin B-Chemical 0
during O 0
the O 0
first O 0
trimester O 0
, O 0
and O 0
a O 0
causal O 0
association O 0
is O 0
probable O 0
. O 0

In O 0
view O 0
of O 0
the O 0
risks O 0
to O 0
both O 0
mother O 0
and O 0
fetus O 0
in O 0
women O 0
with O 0
prosthetic O 0
cardiac O 0
valves O 0
it O 0
is O 0
recommended O 0
that O 0
therapeutic O 0
abortion O 0
be O 0
advised O 0
as O 0
the O 0
first O 0
alternative O 0
. O 0

The O 0
negative O 0
mucosal O 0
potential O 0
: O 0
separating O 0
central O 0
and O 0
peripheral O 0
effects O 0
of O 0
NSAIDs O 0
in O 0
man O 0
. O 0

OBJECTIVE O 0
: O 0
We O 0
wanted O 0
to O 0
test O 0
whether O 0
assessment O 0
of O 0
both O 0
a O 0
central O 0
pain B-Disease 0
- O 0
related O 0
signal O 0
( O 0
chemo O 0
- O 0
somatosensory O 0
evoked O 0
potential O 0
, O 0
CSSEP O 0
) O 0
and O 0
a O 0
concomitantly O 0
recorded O 0
peripheral O 0
signal O 0
( O 0
negative O 0
mucosal O 0
potential O 0
, O 0
NMP O 0
) O 0
allows O 0
for O 0
separation O 0
of O 0
central O 0
and O 0
peripheral O 0
effects O 0
of O 0
NSAIDs O 0
. O 0

For O 0
this O 0
purpose O 0
, O 0
experimental O 0
conditions O 0
were O 0
created O 0
in O 0
which O 0
NSAIDs O 0
had O 0
previously O 0
been O 0
observed O 0
to O 0
produce O 0
effects O 0
on O 0
phasic O 0
and O 0
tonic O 0
pain B-Disease 0
by O 0
either O 0
central O 0
or O 0
peripheral O 0
mechanisms O 0
. O 0

METHODS O 0
: O 0
According O 0
to O 0
a O 0
double O 0
- O 0
blind O 0
, O 0
randomised O 0
, O 0
controlled O 0
, O 0
threefold O 0
cross O 0
- O 0
over O 0
design O 0
, O 0
18 O 0
healthy O 0
subjects O 0
( O 0
11 O 0
males O 0
, O 0
7 O 0
females O 0
; O 0
mean O 0
age O 0
26 O 0
years O 0
) O 0
received O 0
either O 0
placebo O 0
, O 0
400 O 0
mg O 0
ibuprofen B-Chemical 0
, O 0
or O 0
800 O 0
mg O 0
ibuprofen B-Chemical 0
. O 0

Phasic O 0
pain B-Disease 0
was O 0
applied O 0
by O 0
means O 0
of O 0
short O 0
pulses O 0
of O 0
CO2 B-Chemical 0
to O 0
the O 0
nasal O 0
mucosa O 0
( O 0
stimulus O 0
duration O 0
500 O 0
ms O 0
, O 0
interval O 0
approximately O 0
60 O 0
s O 0
) O 0
, O 0
and O 0
tonic O 0
pain B-Disease 0
was O 0
induced O 0
in O 0
the O 0
nasal O 0
cavity O 0
by O 0
means O 0
of O 0
dry O 0
air O 0
of O 0
controlled O 0
temperature O 0
, O 0
humidity O 0
and O 0
flow O 0
rate O 0
( O 0
22 O 0
degrees O 0
C O 0
, O 0
0 O 0
% O 0
relative O 0
humidity O 0
, O 0
145 O 0
ml O 0
. O 0
s O 0
- O 0
1 O 0
) O 0
. O 0

Both O 0
CSSEPs O 0
as O 0
central O 0
and O 0
NMPs O 0
as O 0
peripheral O 0
correlates O 0
of O 0
pain B-Disease 0
were O 0
obtained O 0
in O 0
response O 0
to O 0
the O 0
CO2 B-Chemical 0
stimuli O 0
. O 0

Additionally O 0
, O 0
the O 0
subjects O 0
rated O 0
the O 0
intensity O 0
of O 0
both O 0
phasic O 0
and O 0
tonic O 0
pain B-Disease 0
by O 0
means O 0
of O 0
visual O 0
analogue O 0
scales O 0
. O 0

RESULTS O 0
: O 0
As O 0
described O 0
earlier O 0
, O 0
administration O 0
of O 0
ibuprofen B-Chemical 0
was O 0
followed O 0
by O 0
a O 0
decrease O 0
in O 0
tonic O 0
pain B-Disease 0
but O 0
- O 0
relative O 0
to O 0
placebo O 0
- O 0
an O 0
increase O 0
in O 0
correlates O 0
of O 0
phasic O 0
pain B-Disease 0
, O 0
indicating O 0
a O 0
specific O 0
effect O 0
of O 0
ibuprofen B-Chemical 0
on O 0
the O 0
interaction O 0
between O 0
the O 0
pain B-Disease 0
stimuli O 0
under O 0
these O 0
special O 0
experimental O 0
conditions O 0
. O 0

Based O 0
on O 0
the O 0
similar O 0
behaviour O 0
of O 0
CSSEP O 0
and O 0
NMP O 0
, O 0
it O 0
was O 0
concluded O 0
that O 0
the O 0
pharmacological O 0
process O 0
underlying O 0
this O 0
phenomenon O 0
was O 0
localised O 0
in O 0
the O 0
periphery O 0
. O 0

By O 0
means O 0
of O 0
the O 0
simultaneous O 0
recording O 0
of O 0
interrelated O 0
peripheral O 0
and O 0
central O 0
electrophysiologic O 0
correlates O 0
of O 0
nociception O 0
, O 0
it O 0
was O 0
possible O 0
to O 0
separate O 0
central O 0
and O 0
peripheral O 0
effects O 0
of O 0
an O 0
NSAID O 0
. O 0

The O 0
major O 0
advantage O 0
of O 0
this O 0
pain B-Disease 0
model O 0
is O 0
the O 0
possibility O 0
of O 0
obtaining O 0
peripheral O 0
pain B-Disease 0
- O 0
related O 0
activity O 0
directly O 0
using O 0
a O 0
non O 0
- O 0
invasive O 0
technique O 0
in O 0
humans O 0
. O 0

Effect O 0
of O 0
D B-Chemical 0
- I-Chemical 0
Glucarates I-Chemical 0
on O 0
basic O 0
antibiotic O 0
- O 0
induced O 0
renal B-Disease 0
damage I-Disease 0
in O 0
rats O 0
. O 0

Dehydrated B-Disease 0
rats O 0
regularly O 0
develop O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
following O 0
single O 0
injection O 0
of O 0
aminoglycoside B-Chemical 0
antibiotics O 0
combined O 0
with O 0
dextran O 0
or O 0
of O 0
antibiotics O 0
only O 0
. O 0

Oral O 0
administration O 0
of O 0
2 B-Chemical 0
, I-Chemical 0
5 I-Chemical 0
- I-Chemical 0
di I-Chemical 0
- I-Chemical 0
O I-Chemical 0
- I-Chemical 0
acetyl I-Chemical 0
- I-Chemical 0
D I-Chemical 0
- I-Chemical 0
glucaro I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
6 I-Chemical 0
, I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
dilactone I-Chemical 0
protected O 0
rats O 0
against O 0
renal B-Disease 0
failure I-Disease 0
induced O 0
by O 0
kanamycin B-Chemical 0
- O 0
dextran O 0
. O 0

The O 0
protective O 0
effect O 0
was O 0
prevalent O 0
among O 0
D B-Chemical 0
- I-Chemical 0
glucarates I-Chemical 0
, O 0
and O 0
also O 0
to O 0
other O 0
saccharic B-Chemical 0
acid I-Chemical 0
, O 0
hexauronic B-Chemical 0
acids I-Chemical 0
and O 0
hexaaldonic B-Chemical 0
acids I-Chemical 0
, O 0
although O 0
to O 0
a O 0
lesser O 0
degree O 0
, O 0
but O 0
not O 0
to O 0
a O 0
hexaaldose O 0
, O 0
sugar B-Chemical 0
alcohols I-Chemical 0
, O 0
substances O 0
inthe O 0
TCA B-Chemical 0
cycle O 0
and O 0
other O 0
acidic O 0
compounds O 0
. O 0

D B-Chemical 0
- I-Chemical 0
Glucarates I-Chemical 0
were O 0
effective O 0
against O 0
renal B-Disease 0
damage I-Disease 0
induced O 0
by O 0
peptide O 0
antibiotics O 0
as O 0
well O 0
as O 0
various O 0
aminoglycoside B-Chemical 0
antibitocis O 0
. O 0

Dose O 0
- O 0
responses O 0
were O 0
observed O 0
in O 0
the O 0
protective O 0
effect O 0
of O 0
D B-Chemical 0
- I-Chemical 0
Glucarates I-Chemical 0
. O 0

With O 0
a O 0
D B-Chemical 0
- I-Chemical 0
glucarate I-Chemical 0
of O 0
a O 0
fixed O 0
size O 0
of O 0
dose O 0
, O 0
approximately O 0
the O 0
same O 0
degree O 0
of O 0
protection O 0
was O 0
obtained O 0
against O 0
renal B-Disease 0
damages I-Disease 0
induced O 0
by O 0
different O 0
basic O 0
antibiotics O 0
despite O 0
large O 0
disparities O 0
in O 0
administration O 0
doses O 0
of O 0
different O 0
antibiotics O 0
. O 0

D B-Chemical 0
- I-Chemical 0
Glucarates I-Chemical 0
had O 0
the O 0
ability O 0
to O 0
prevent O 0
renal B-Disease 0
damage I-Disease 0
but O 0
not O 0
to O 0
cure O 0
it O 0
. O 0

Rats O 0
excreted O 0
acidic O 0
urine O 0
when O 0
they O 0
were O 0
spared O 0
from O 0
renal B-Disease 0
lesions I-Disease 0
by O 0
monosaccharides B-Chemical 0
. O 0

The O 0
reduction O 0
effect O 0
of O 0
D B-Chemical 0
- I-Chemical 0
glucarates I-Chemical 0
against O 0
nephrotoxicity B-Disease 0
of O 0
basic O 0
antibiotics O 0
was O 0
discussed O 0
. O 0

Acute O 0
severe O 0
depression B-Disease 0
following O 0
peri O 0
- O 0
operative O 0
ondansetron B-Chemical 0
. O 0

A O 0
41 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
a O 0
strong O 0
history O 0
of O 0
postoperative B-Disease 0
nausea I-Disease 0
and I-Disease 0
vomiting I-Disease 0
presented O 0
for O 0
abdominal O 0
hysterectomy O 0
3 O 0
months O 0
after O 0
a O 0
previous O 0
anaesthetic O 0
where O 0
ondansetron B-Chemical 0
prophylaxis O 0
had O 0
been O 0
used O 0
. O 0

She O 0
had O 0
developed O 0
a O 0
severe O 0
acute O 0
major B-Disease 0
depression I-Disease 0
disorder I-Disease 0
almost O 0
immediately O 0
thereafter O 0
, O 0
possibly O 0
related O 0
to O 0
the O 0
use O 0
of O 0
a O 0
serotonin B-Chemical 0
antagonist O 0
. O 0

Nine O 0
years O 0
before O 0
she O 0
had O 0
experienced O 0
a O 0
self O 0
- O 0
limited O 0
puerperal O 0
depressive B-Disease 0
episode I-Disease 0
. O 0

Anaesthesia O 0
with O 0
a O 0
propofol B-Chemical 0
infusion O 0
and O 0
avoidance O 0
of O 0
serotonin B-Chemical 0
antagonists O 0
provided O 0
a O 0
nausea B-Disease 0
- O 0
free O 0
postoperative O 0
course O 0
without O 0
exacerbation O 0
of O 0
the O 0
depression B-Disease 0
disorder I-Disease 0
. O 0

Hypertensive B-Disease 0
response O 0
during O 0
dobutamine B-Chemical 0
stress O 0
echocardiography O 0
. O 0

Among O 0
3 O 0
, O 0
129 O 0
dobutamine B-Chemical 0
stress O 0
echocardiographic O 0
studies O 0
, O 0
a O 0
hypertensive B-Disease 0
response O 0
, O 0
defined O 0
as O 0
systolic O 0
blood O 0
pressure O 0
( O 0
BP O 0
) O 0
> O 0
or O 0
= O 0
220 O 0
mm O 0
Hg O 0
and O 0
/ O 0
or O 0
diastolic O 0
BP O 0
> O 0
or O 0
= O 0
110 O 0
mm O 0
Hg O 0
, O 0
occurred O 0
in O 0
30 O 0
patients O 0
( O 0
1 O 0
% O 0
) O 0
. O 0

Patients O 0
with O 0
this O 0
response O 0
more O 0
often O 0
had O 0
a O 0
history O 0
of O 0
hypertension B-Disease 0
and O 0
had O 0
higher O 0
resting O 0
systolic O 0
and O 0
diastolic O 0
BP O 0
before O 0
dobutamine B-Chemical 0
infusion O 0
. O 0

Continuously O 0
nebulized O 0
albuterol B-Chemical 0
in O 0
severe O 0
exacerbations O 0
of O 0
asthma B-Disease 0
in O 0
adults O 0
: O 0
a O 0
case O 0
- O 0
controlled O 0
study O 0
. O 0

A O 0
retrospective O 0
, O 0
case O 0
- O 0
controlled O 0
analysis O 0
comparing O 0
patients O 0
admitted O 0
to O 0
a O 0
medical O 0
intensive O 0
care O 0
unit O 0
with O 0
severe O 0
exacerbations O 0
of O 0
asthma B-Disease 0
who O 0
received O 0
continuously O 0
nebulized O 0
albuterol B-Chemical 0
( O 0
CNA O 0
) O 0
versus O 0
intermittent O 0
albuterol B-Chemical 0
( O 0
INA O 0
) O 0
treatments O 0
is O 0
reported O 0
. O 0

Forty O 0
matched O 0
pairs O 0
of O 0
patients O 0
with O 0
asthma B-Disease 0
are O 0
compared O 0
. O 0

CNA O 0
was O 0
administered O 0
for O 0
a O 0
mean O 0
of O 0
11 O 0
+ O 0
/ O 0
- O 0
10 O 0
hr O 0
. O 0

The O 0
incidence O 0
of O 0
cardiac B-Disease 0
dysrhythmias I-Disease 0
was O 0
similar O 0
between O 0
groups O 0
. O 0

Symptomatic O 0
hypokalemia B-Disease 0
did O 0
not O 0
occur O 0
. O 0

CNA O 0
patients O 0
had O 0
higher O 0
heart O 0
rates O 0
during O 0
treatment O 0
, O 0
which O 0
may O 0
reflect O 0
severity O 0
of O 0
illness O 0
. O 0

The O 0
incidence O 0
of O 0
intubation O 0
was O 0
similar O 0
. O 0

We O 0
conclude O 0
that O 0
CNA O 0
and O 0
INA O 0
demonstrated O 0
similar O 0
profiles O 0
with O 0
regard O 0
to O 0
safety O 0
, O 0
morbidity O 0
, O 0
and O 0
mortality O 0
. O 0

Paraplegia B-Disease 0
following O 0
intrathecal O 0
methotrexate B-Chemical 0
: O 0
report O 0
of O 0
a O 0
case O 0
and O 0
review O 0
of O 0
the O 0
literature O 0
. O 0

A O 0
patient O 0
who O 0
developed O 0
paraplegia B-Disease 0
following O 0
the O 0
intrathecal O 0
instillation O 0
of O 0
methotrexate B-Chemical 0
is O 0
discribed O 0
. O 0

The O 0
ten O 0
previously O 0
reported O 0
cases O 0
of O 0
this O 0
unusual O 0
complication O 0
are O 0
reviewed O 0
. O 0

The O 0
following O 0
factors O 0
appear O 0
to O 0
predispose O 0
to O 0
the O 0
development O 0
of O 0
this O 0
complication O 0
: O 0
abnormal O 0
cerebrospinal O 0
dynamics O 0
related O 0
to O 0
the O 0
presence O 0
of O 0
central B-Disease 0
nervous I-Disease 0
system I-Disease 0
leukemia I-Disease 0
, O 0
and O 0
epidural O 0
cerebrospinal O 0
leakage O 0
; O 0
elevated O 0
cerebrospinal O 0
fluid O 0
methothexate B-Chemical 0
concentration O 0
related O 0
to O 0
abnormal O 0
cerebrospinal O 0
fluid O 0
dynamics O 0
and O 0
to O 0
inappropriately O 0
high O 0
methotrexate B-Chemical 0
doses O 0
based O 0
on O 0
body O 0
surface O 0
area O 0
calculations O 0
in O 0
older O 0
children O 0
and O 0
adults O 0
; O 0
the O 0
presence O 0
of O 0
neurotoxic B-Disease 0
preservatives O 0
in O 0
commercially O 0
available O 0
methotrexate B-Chemical 0
preparations O 0
and O 0
diluents O 0
; O 0
and O 0
the O 0
use O 0
of O 0
methotrexate B-Chemical 0
diluents O 0
of O 0
unphysiologic O 0
pH O 0
, O 0
ionic O 0
content O 0
and O 0
osmolarity O 0
. O 0

The O 0
role O 0
of O 0
methotrexate B-Chemical 0
contaminants O 0
, O 0
local O 0
folate B-Disease 0
deficiency I-Disease 0
, O 0
and O 0
cranial O 0
irradiation O 0
in O 0
the O 0
pathogenesis O 0
of O 0
intrathecal O 0
methotrexate B-Chemical 0
toxicity B-Disease 0
is O 0
unclear O 0
. O 0

The O 0
incidence O 0
of O 0
neurotoxicity B-Disease 0
may O 0
be O 0
reduced O 0
by O 0
employing O 0
lower O 0
doses O 0
of O 0
methotrexate B-Chemical 0
in O 0
the O 0
presence O 0
of O 0
central B-Disease 0
nervous I-Disease 0
system I-Disease 0
leukemia I-Disease 0
, O 0
in O 0
older O 0
children O 0
and O 0
adults O 0
, O 0
and O 0
in O 0
the O 0
presence O 0
of O 0
epidural O 0
leakage O 0
. O 0

Only O 0
preservative O 0
- O 0
free O 0
methotrexate B-Chemical 0
in O 0
Elliott O 0
' O 0
s O 0
B O 0
Solution O 0
at O 0
a O 0
concentration O 0
of O 0
not O 0
more O 0
than O 0
1 O 0
mg O 0
/ O 0
ml O 0
should O 0
be O 0
used O 0
for O 0
intrathecal O 0
administration O 0
. O 0

Periodic O 0
monitoring O 0
of O 0
cerebruspinal O 0
fluid O 0
methotrexate B-Chemical 0
levels O 0
may O 0
be O 0
predictive O 0
of O 0
the O 0
development O 0
of O 0
serious O 0
neurotoxicity B-Disease 0
. O 0

Hyperosmolar B-Disease 0
nonketotic I-Disease 0
coma I-Disease 0
precipitated O 0
by O 0
lithium B-Chemical 0
- O 0
induced O 0
nephrogenic B-Disease 0
diabetes I-Disease 0
insipidus I-Disease 0
. O 0

A O 0
45 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
, O 0
with O 0
a O 0
10 O 0
- O 0
year O 0
history O 0
of O 0
manic B-Disease 0
depression I-Disease 0
treated O 0
with O 0
lithium B-Chemical 0
, O 0
was O 0
admitted O 0
with O 0
hyperosmolar B-Disease 0
, I-Disease 0
nonketotic I-Disease 0
coma I-Disease 0
. O 0

He O 0
gave O 0
a O 0
five O 0
- O 0
year O 0
history O 0
of O 0
polyuria B-Disease 0
and O 0
polydipsia B-Disease 0
, O 0
during O 0
which O 0
time O 0
urinalysis O 0
had O 0
been O 0
negative O 0
for O 0
glucose B-Chemical 0
. O 0

After O 0
recovery O 0
from O 0
hyperglycaemia B-Disease 0
, O 0
he O 0
remained O 0
polyuric B-Disease 0
despite O 0
normal O 0
blood O 0
glucose B-Chemical 0
concentrations O 0
; O 0
water O 0
deprivation O 0
testing O 0
indicated O 0
nephrogenic B-Disease 0
diabetes I-Disease 0
insipidus I-Disease 0
, O 0
likely O 0
to O 0
be O 0
lithium B-Chemical 0
- O 0
induced O 0
. O 0

We O 0
hypothesize O 0
that O 0
when O 0
this O 0
man O 0
developed O 0
type B-Disease 0
2 I-Disease 0
diabetes I-Disease 0
, O 0
chronic O 0
polyuria B-Disease 0
due O 0
to O 0
nephrogenic B-Disease 0
diabetes I-Disease 0
insipidus I-Disease 0
was O 0
sufficient O 0
to O 0
precipitate O 0
hyperosmolar O 0
dehydration B-Disease 0
. O 0

Effects O 0
of O 0
the O 0
intracoronary O 0
infusion O 0
of O 0
cocaine B-Chemical 0
on O 0
left O 0
ventricular O 0
systolic O 0
and O 0
diastolic O 0
function O 0
in O 0
humans O 0
. O 0

BACKGROUND O 0
: O 0
In O 0
dogs O 0
, O 0
a O 0
large O 0
amount O 0
of O 0
intravenous O 0
cocaine B-Chemical 0
causes O 0
a O 0
profound O 0
deterioration B-Disease 0
of I-Disease 0
left I-Disease 0
ventricular I-Disease 0
( I-Disease 0
LV I-Disease 0
) I-Disease 0
systolic I-Disease 0
function I-Disease 0
and O 0
an O 0
increase O 0
in O 0
LV O 0
end O 0
- O 0
diastolic O 0
pressure O 0
. O 0

This O 0
study O 0
was O 0
done O 0
to O 0
assess O 0
the O 0
influence O 0
of O 0
a O 0
high O 0
intracoronary O 0
cocaine B-Chemical 0
concentration O 0
on O 0
LV O 0
systolic O 0
and O 0
diastolic O 0
function O 0
in O 0
humans O 0
. O 0

METHODS O 0
AND O 0
RESULTS O 0
: O 0
In O 0
20 O 0
patients O 0
( O 0
14 O 0
men O 0
and O 0
6 O 0
women O 0
aged O 0
39 O 0
to O 0
72 O 0
years O 0
) O 0
referred O 0
for O 0
cardiac O 0
catheterization O 0
for O 0
the O 0
evaluation O 0
of O 0
chest B-Disease 0
pain I-Disease 0
, O 0
we O 0
measured O 0
heart O 0
rate O 0
, O 0
systemic O 0
arterial O 0
pressure O 0
, O 0
LV O 0
pressure O 0
and O 0
its O 0
first O 0
derivative O 0
( O 0
dP O 0
/ O 0
dt O 0
) O 0
, O 0
and O 0
LV O 0
volumes O 0
and O 0
ejection O 0
fraction O 0
before O 0
and O 0
during O 0
the O 0
final O 0
2 O 0
to O 0
3 O 0
minutes O 0
of O 0
a O 0
15 O 0
- O 0
minute O 0
intracoronary O 0
infusion O 0
of O 0
saline O 0
( O 0
n O 0
= O 0
10 O 0
, O 0
control O 0
subjects O 0
) O 0
or O 0
cocaine B-Chemical 0
hydrochloride I-Chemical 0
1 O 0
mg O 0
/ O 0
min O 0
( O 0
n O 0
= O 0
10 O 0
) O 0
. O 0

No O 0
variable O 0
changed O 0
with O 0
saline O 0
. O 0

With O 0
cocaine B-Chemical 0
, O 0
the O 0
drug O 0
concentration O 0
in O 0
blood O 0
obtained O 0
from O 0
the O 0
coronary O 0
sinus O 0
was O 0
3 O 0
. O 0
0 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
4 O 0
( O 0
mean O 0
+ O 0
/ O 0
- O 0
SD O 0
) O 0
mg O 0
/ O 0
L O 0
, O 0
similar O 0
in O 0
magnitude O 0
to O 0
the O 0
blood O 0
cocaine B-Chemical 0
concentration O 0
reported O 0
in O 0
abusers O 0
dying O 0
of O 0
cocaine B-Chemical 0
intoxication O 0
. O 0

Cocaine B-Chemical 0
induced O 0
no O 0
significant O 0
change O 0
in O 0
heart O 0
rate O 0
, O 0
LV O 0
dP O 0
/ O 0
dt O 0
( O 0
positive O 0
or O 0
negative O 0
) O 0
, O 0
or O 0
LV O 0
end O 0
- O 0
diastolic O 0
volume O 0
, O 0
but O 0
it O 0
caused O 0
an O 0
increase O 0
in O 0
systolic O 0
and O 0
mean O 0
arterial O 0
pressures O 0
, O 0
LV O 0
end O 0
- O 0
diastolic O 0
pressure O 0
, O 0
and O 0
LV O 0
end O 0
- O 0
systolic O 0
volume O 0
, O 0
as O 0
well O 0
as O 0
a O 0
decrease O 0
in O 0
LV O 0
ejection O 0
fraction O 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
humans O 0
, O 0
the O 0
intracoronary O 0
infusion O 0
of O 0
cocaine B-Chemical 0
sufficient O 0
in O 0
amount O 0
to O 0
achieve O 0
a O 0
high O 0
drug O 0
concentration O 0
in O 0
coronary O 0
sinus O 0
blood O 0
causes O 0
a O 0
deterioration B-Disease 0
of I-Disease 0
LV I-Disease 0
systolic I-Disease 0
and I-Disease 0
diastolic I-Disease 0
performance I-Disease 0
. O 0

Ascending O 0
dose O 0
tolerance O 0
study O 0
of O 0
intramuscular O 0
carbetocin B-Chemical 0
administered O 0
after O 0
normal O 0
vaginal O 0
birth O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
determine O 0
the O 0
maximum O 0
tolerated O 0
dose O 0
( O 0
MTD O 0
) O 0
of O 0
carbetocin B-Chemical 0
( O 0
a O 0
long O 0
- O 0
acting O 0
synthetic O 0
analogue O 0
of O 0
oxytocin B-Chemical 0
) O 0
, O 0
when O 0
administered O 0
immediately O 0
after O 0
vaginal O 0
delivery O 0
at O 0
term O 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
Carbetocin B-Chemical 0
was O 0
given O 0
as O 0
an O 0
intramuscular O 0
injection O 0
immediately O 0
after O 0
the O 0
birth O 0
of O 0
the O 0
infant O 0
in O 0
45 O 0
healthy O 0
women O 0
with O 0
normal O 0
singleton O 0
pregnancies O 0
who O 0
delivered O 0
vaginally O 0
at O 0
term O 0
. O 0

Dosage O 0
groups O 0
of O 0
15 O 0
, O 0
30 O 0
, O 0
50 O 0
, O 0
75 O 0
, O 0
100 O 0
, O 0
125 O 0
, O 0
150 O 0
, O 0
175 O 0
or O 0
200 O 0
microg O 0
carbetocin B-Chemical 0
were O 0
assigned O 0
to O 0
blocks O 0
of O 0
three O 0
women O 0
according O 0
to O 0
the O 0
continual O 0
reassessment O 0
method O 0
( O 0
CRM O 0
) O 0
. O 0

RESULTS O 0
: O 0
All O 0
dosage O 0
groups O 0
consisted O 0
of O 0
three O 0
women O 0
, O 0
except O 0
those O 0
with O 0
100 O 0
microg O 0
( O 0
n O 0
= O 0
6 O 0
) O 0
and O 0
200 O 0
microg O 0
( O 0
n O 0
= O 0
18 O 0
) O 0
. O 0

Recorded O 0
were O 0
dose O 0
- O 0
limiting O 0
adverse O 0
events O 0
: O 0
hyper B-Disease 0
- I-Disease 0
or I-Disease 0
hypotension I-Disease 0
( O 0
three O 0
) O 0
, O 0
severe O 0
abdominal B-Disease 0
pain I-Disease 0
( O 0
0 O 0
) O 0
, O 0
vomiting B-Disease 0
( O 0
0 O 0
) O 0
and O 0
retained B-Disease 0
placenta I-Disease 0
( O 0
four O 0
) O 0
. O 0

Serious O 0
adverse O 0
events O 0
occurred O 0
in O 0
seven O 0
women O 0
: O 0
six O 0
cases O 0
with O 0
blood B-Disease 0
loss I-Disease 0
> O 0
or O 0
= O 0
1000 O 0
ml O 0
, O 0
four O 0
cases O 0
of O 0
manual O 0
placenta O 0
removal O 0
, O 0
five O 0
cases O 0
of O 0
additional O 0
oxytocics O 0
administration O 0
and O 0
five O 0
cases O 0
of O 0
blood O 0
transfusion O 0
. O 0

Maximum O 0
blood B-Disease 0
loss I-Disease 0
was O 0
greatest O 0
at O 0
the O 0
upper O 0
and O 0
lower O 0
dose O 0
levels O 0
, O 0
and O 0
lowest O 0
in O 0
the O 0
70 O 0
- O 0
125 O 0
microg O 0
dose O 0
range O 0
. O 0

Four O 0
out O 0
of O 0
six O 0
cases O 0
with O 0
blood B-Disease 0
loss I-Disease 0
> O 0
or O 0
= O 0
1000 O 0
ml O 0
occurred O 0
in O 0
the O 0
200 O 0
microg O 0
group O 0
. O 0

The O 0
majority O 0
of O 0
additional O 0
administration O 0
of O 0
oxytocics O 0
( O 0
4 O 0
/ O 0
5 O 0
) O 0
and O 0
blood O 0
transfusion O 0
( O 0
3 O 0
/ O 0
5 O 0
) O 0
occurred O 0
in O 0
the O 0
dose O 0
groups O 0
of O 0
200 O 0
microg O 0
. O 0

All O 0
retained O 0
placentae O 0
were O 0
found O 0
in O 0
the O 0
group O 0
of O 0
200 O 0
microg O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
MTD O 0
was O 0
calculated O 0
to O 0
be O 0
at O 0
200 O 0
microg O 0
carbetocin B-Chemical 0
. O 0

Heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
, O 0
paradoxical O 0
thromboembolism B-Disease 0
, O 0
and O 0
other O 0
side O 0
effects O 0
of O 0
heparin B-Chemical 0
therapy O 0
. O 0

Although O 0
several O 0
new O 0
anticoagulant O 0
drugs O 0
are O 0
in O 0
development O 0
, O 0
heparin B-Chemical 0
remains O 0
the O 0
drug O 0
of O 0
choice O 0
for O 0
most O 0
anticoagulation O 0
needs O 0
. O 0

The O 0
clinical O 0
effects O 0
of O 0
heparin B-Chemical 0
are O 0
meritorious O 0
, O 0
but O 0
side O 0
effects O 0
do O 0
exist O 0
. O 0

Important O 0
untoward O 0
effects O 0
of O 0
heparin B-Chemical 0
therapy O 0
including O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
, O 0
heparin B-Chemical 0
- O 0
associated O 0
osteoporosis B-Disease 0
, O 0
eosinophilia B-Disease 0
, O 0
skin B-Disease 0
reactions I-Disease 0
, O 0
allergic B-Disease 0
reactions I-Disease 0
other O 0
than O 0
thrombocytopenia B-Disease 0
and O 0
alopecia B-Disease 0
will O 0
be O 0
discussed O 0
in O 0
this O 0
article O 0
. O 0

Nonopaque O 0
crystal O 0
deposition O 0
causing O 0
ureteric B-Disease 0
obstruction I-Disease 0
in O 0
patients O 0
with O 0
HIV O 0
undergoing O 0
indinavir B-Chemical 0
therapy O 0
. O 0

OBJECTIVE O 0
: O 0
We O 0
describe O 0
the O 0
unique O 0
CT O 0
features O 0
of O 0
ureteric B-Disease 0
calculi I-Disease 0
in O 0
six O 0
HIV B-Disease 0
- I-Disease 0
infected I-Disease 0
patients O 0
receiving O 0
indinavir B-Chemical 0
, O 0
the O 0
most O 0
commonly O 0
used O 0
HIV O 0
protease O 0
inhibitor O 0
, O 0
which O 0
is O 0
associated O 0
with O 0
an O 0
increased O 0
incidence O 0
of O 0
urolithiasis B-Disease 0
. O 0

CONCLUSION O 0
: O 0
Ureteric B-Disease 0
obstruction I-Disease 0
caused O 0
by O 0
precipitated O 0
indinavir B-Chemical 0
crystals O 0
may O 0
be O 0
difficult O 0
to O 0
diagnose O 0
with O 0
unenhanced O 0
CT O 0
. O 0

The O 0
calculi O 0
are O 0
not O 0
opaque O 0
, O 0
and O 0
secondary O 0
signs O 0
of O 0
obstruction O 0
may O 0
be O 0
absent O 0
or O 0
minimal O 0
and O 0
should O 0
be O 0
sought O 0
carefully O 0
. O 0

Images O 0
may O 0
need O 0
to O 0
be O 0
obtained O 0
using O 0
i O 0
. O 0
v O 0
. O 0
contrast O 0
material O 0
to O 0
enable O 0
diagnosis O 0
of O 0
ureteric B-Disease 0
stones I-Disease 0
or I-Disease 0
obstruction I-Disease 0
in O 0
patients O 0
with O 0
HIV B-Disease 0
infection I-Disease 0
who O 0
receive O 0
indinavir B-Chemical 0
therapy O 0
. O 0

Ischemic B-Disease 0
colitis I-Disease 0
and O 0
sumatriptan B-Chemical 0
use O 0
. O 0

Sumatriptan B-Chemical 0
succinate I-Chemical 0
, O 0
a O 0
serotonin B-Chemical 0
- O 0
1 O 0
( O 0
5 B-Chemical 0
- I-Chemical 0
hydroxytryptamine I-Chemical 0
- O 0
1 O 0
) O 0
receptor O 0
agonist O 0
, O 0
is O 0
an O 0
antimigraine O 0
drug O 0
that O 0
is O 0
reported O 0
to O 0
act O 0
by O 0
selectively O 0
constricting O 0
intracranial O 0
arteries O 0
. O 0

Recently O 0
, O 0
vasopressor O 0
responses O 0
that O 0
are O 0
distinct O 0
from O 0
the O 0
cranial O 0
circulation O 0
have O 0
been O 0
demonstrated O 0
to O 0
occur O 0
in O 0
the O 0
systemic O 0
, O 0
pulmonary O 0
, O 0
and O 0
coronary O 0
circulations O 0
. O 0

Cases O 0
have O 0
been O 0
published O 0
of O 0
coronary B-Disease 0
vasospasm I-Disease 0
, O 0
myocardial B-Disease 0
ischemia I-Disease 0
, O 0
and O 0
myocardial B-Disease 0
infarction I-Disease 0
occurring O 0
after O 0
sumatriptan B-Chemical 0
use O 0
. O 0

We O 0
report O 0
on O 0
the O 0
development O 0
of O 0
8 O 0
serious O 0
cases O 0
of O 0
ischemic B-Disease 0
colitis I-Disease 0
in O 0
patients O 0
with O 0
migraine B-Disease 0
treated O 0
with O 0
sumatriptan B-Chemical 0
. O 0

Pallidotomy O 0
with O 0
the O 0
gamma O 0
knife O 0
: O 0
a O 0
positive O 0
experience O 0
. O 0

51 O 0
patients O 0
with O 0
medically O 0
refractory O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
underwent O 0
stereotactic O 0
posteromedial O 0
pallidotomy O 0
between O 0
August O 0
1993 O 0
and O 0
February O 0
1997 O 0
for O 0
treatment O 0
of O 0
bradykinesia B-Disease 0
, O 0
rigidity B-Disease 0
, O 0
and O 0
L B-Chemical 0
- I-Chemical 0
DOPA I-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
. O 0

In O 0
29 O 0
patients O 0
, O 0
the O 0
pallidotomies O 0
were O 0
performed O 0
with O 0
the O 0
Leksell O 0
Gamma O 0
Knife O 0
and O 0
in O 0
22 O 0
they O 0
were O 0
performed O 0
with O 0
the O 0
standard O 0
radiofrequency O 0
( O 0
RF O 0
) O 0
method O 0
. O 0

Clinical O 0
assessment O 0
as O 0
well O 0
as O 0
blinded O 0
ratings O 0
of O 0
Unified O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
Disease I-Disease 0
Rating O 0
Scale O 0
( O 0
UPDRS O 0
) O 0
scores O 0
were O 0
carried O 0
out O 0
pre O 0
- O 0
and O 0
postoperatively O 0
. O 0

Mean O 0
follow O 0
- O 0
up O 0
time O 0
is O 0
20 O 0
. O 0
6 O 0
months O 0
( O 0
range O 0
6 O 0
- O 0
48 O 0
) O 0
and O 0
all O 0
except O 0
4 O 0
patients O 0
have O 0
been O 0
followed O 0
more O 0
than O 0
one O 0
year O 0
. O 0

85 O 0
percent O 0
of O 0
patients O 0
with O 0
dyskinesias B-Disease 0
were O 0
relieved O 0
of O 0
symptoms O 0
, O 0
regardless O 0
of O 0
whether O 0
the O 0
pallidotomies O 0
were O 0
performed O 0
with O 0
the O 0
Gamma O 0
Knife O 0
or O 0
radiofrequency O 0
methods O 0
. O 0

About O 0
2 O 0
/ O 0
3 O 0
of O 0
the O 0
patients O 0
in O 0
both O 0
Gamma O 0
Knife O 0
and O 0
radiofrequency O 0
groups O 0
showed O 0
improvements O 0
in O 0
bradykinesia B-Disease 0
and O 0
rigidity B-Disease 0
, O 0
although O 0
when O 0
considered O 0
as O 0
a O 0
group O 0
neither O 0
the O 0
Gamma O 0
Knife O 0
nor O 0
the O 0
radiofrequency O 0
group O 0
showed O 0
statistically O 0
significant O 0
improvements O 0
in O 0
UPDRS O 0
scores O 0
. O 0

One O 0
patient O 0
in O 0
the O 0
Gamma O 0
Knife O 0
group O 0
( O 0
3 O 0
. O 0
4 O 0
% O 0
) O 0
developed O 0
a O 0
homonymous B-Disease 0
hemianopsia I-Disease 0
9 O 0
months O 0
following O 0
treatment O 0
and O 0
5 O 0
patients O 0
( O 0
27 O 0
. O 0
7 O 0
% O 0
) O 0
in O 0
the O 0
radiofrequency O 0
group O 0
became O 0
transiently O 0
confused O 0
postoperatively O 0
. O 0

No O 0
other O 0
complications O 0
were O 0
seen O 0
. O 0

Gamma O 0
Knife O 0
pallidotomy O 0
is O 0
as O 0
effective O 0
as O 0
radiofrequency O 0
pallidotomy O 0
in O 0
controlling O 0
certain O 0
of O 0
the O 0
symptoms O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

It O 0
may O 0
be O 0
the O 0
only O 0
practical O 0
technique O 0
available O 0
in O 0
certain O 0
patients O 0
, O 0
such O 0
as O 0
those O 0
who O 0
take O 0
anticoagulants O 0
, O 0
have O 0
bleeding B-Disease 0
diatheses O 0
or O 0
serious O 0
systemic O 0
medical O 0
illnesses O 0
. O 0

It O 0
is O 0
a O 0
viable O 0
option O 0
for O 0
other O 0
patients O 0
as O 0
well O 0
. O 0

Centrally O 0
mediated O 0
cardiovascular O 0
effects O 0
of O 0
intracisternal O 0
application O 0
of O 0
carbachol B-Chemical 0
in O 0
anesthetized O 0
rats O 0
. O 0

The O 0
pressor O 0
response O 0
to O 0
the O 0
intracisternal O 0
( O 0
i O 0
. O 0
c O 0
. O 0
) O 0
injection O 0
of O 0
carbachol B-Chemical 0
( O 0
1 O 0
mug O 0
) O 0
in O 0
anesthetized O 0
rats O 0
was O 0
analyzed O 0
. O 0

This O 0
response O 0
was O 0
significantly O 0
reduced O 0
by O 0
the O 0
intravenous O 0
( O 0
i O 0
. O 0
v O 0
. O 0
) O 0
injection O 0
of O 0
guanethidine B-Chemical 0
( O 0
5 O 0
mg O 0
) O 0
, O 0
hexamethonium B-Chemical 0
( O 0
10 O 0
mg O 0
) O 0
or O 0
phentolamine B-Chemical 0
( O 0
5 O 0
mg O 0
) O 0
, O 0
and O 0
conversely O 0
, O 0
potentiated O 0
by O 0
i O 0
. O 0
v O 0
. O 0
desmethylimipramine B-Chemical 0
( O 0
0 O 0
. O 0
3 O 0
mg O 0
) O 0
, O 0
while O 0
propranolol B-Chemical 0
( O 0
0 O 0
. O 0
5 O 0
mg O 0
) O 0
i O 0
. O 0
v O 0
. O 0
selectively O 0
inhibited O 0
the O 0
enlargement B-Disease 0
of I-Disease 0
pulse I-Disease 0
pressure I-Disease 0
and O 0
the O 0
tachycardia B-Disease 0
following O 0
i O 0
. O 0
c O 0
. O 0
carbachol B-Chemical 0
( O 0
1 O 0
mug O 0
) O 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
the O 0
pressor O 0
response O 0
to O 0
i O 0
. O 0
c O 0
. O 0
carbachol B-Chemical 0
( O 0
1 O 0
mug O 0
) O 0
was O 0
almost O 0
completely O 0
blocked O 0
by O 0
i O 0
. O 0
c O 0
. O 0
atropine B-Chemical 0
( O 0
3 O 0
mug O 0
) O 0
or O 0
hexamethonium B-Chemical 0
( O 0
500 O 0
mug O 0
) O 0
, O 0
and O 0
significantly O 0
reduced O 0
by O 0
i O 0
. O 0
c O 0
. O 0
chlorpromazine B-Chemical 0
( O 0
50 O 0
mug O 0
) O 0
but O 0
significantly O 0
potentiated O 0
by O 0
i O 0
. O 0
c O 0
. O 0
desmethylimipramine B-Chemical 0
( O 0
30 O 0
mug O 0
) O 0
. O 0

The O 0
pressor O 0
response O 0
to O 0
i O 0
. O 0
c O 0
. O 0
carbachol B-Chemical 0
( O 0
1 O 0
mug O 0
) O 0
remained O 0
unchanged O 0
after O 0
sectioning O 0
of O 0
the O 0
bilateral O 0
cervical O 0
vagal O 0
nerves O 0
but O 0
disappeared O 0
after O 0
sectioning O 0
of O 0
the O 0
spinal O 0
cord O 0
( O 0
C7 O 0
- O 0
C8 O 0
) O 0
. O 0

From O 0
the O 0
above O 0
result O 0
it O 0
is O 0
suggested O 0
that O 0
the O 0
pressor O 0
response O 0
to O 0
i O 0
. O 0
c O 0
. O 0
carbachol B-Chemical 0
ortral O 0
and O 0
peripheral O 0
adrenergic O 0
mechanisms O 0
, O 0
and O 0
that O 0
the O 0
sympathetic O 0
trunk O 0
is O 0
the O 0
main O 0
pathway O 0
. O 0

Neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
and O 0
methylphenidate B-Chemical 0
. O 0

A O 0
1 O 0
- O 0
year O 0
- O 0
old O 0
female O 0
presented O 0
with O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
probably O 0
caused O 0
by O 0
methylphenidate B-Chemical 0
. O 0

She O 0
had O 0
defects O 0
in O 0
the O 0
supratentorial O 0
brain O 0
including O 0
the O 0
basal O 0
ganglia O 0
and O 0
the O 0
striatum O 0
( O 0
multicystic B-Disease 0
encephalomalacia I-Disease 0
) O 0
due O 0
to O 0
severe O 0
perinatal O 0
hypoxic B-Disease 0
- I-Disease 0
ischemic I-Disease 0
encephalopathy I-Disease 0
, O 0
which O 0
was O 0
considered O 0
to O 0
be O 0
a O 0
possible O 0
predisposing O 0
factor O 0
causing O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
. O 0

A O 0
dopaminergic O 0
blockade O 0
mechanism O 0
generally O 0
is O 0
accepted O 0
as O 0
the O 0
pathogenesis O 0
of O 0
this O 0
syndrome O 0
. O 0

However O 0
, O 0
methylphenidate B-Chemical 0
is O 0
a O 0
dopamine B-Chemical 0
agonist O 0
via O 0
the O 0
inhibition O 0
of O 0
uptake O 0
of O 0
dopamine B-Chemical 0
, O 0
and O 0
therefore O 0
dopaminergic O 0
systems O 0
in O 0
the O 0
brainstem O 0
( O 0
mainly O 0
the O 0
midbrain O 0
) O 0
and O 0
the O 0
spinal O 0
cord O 0
were O 0
unlikely O 0
to O 0
participate O 0
in O 0
the O 0
onset O 0
of O 0
this O 0
syndrome O 0
. O 0

A O 0
relative O 0
gamma B-Chemical 0
- I-Chemical 0
aminobutyric I-Chemical 0
acid I-Chemical 0
- O 0
ergic O 0
deficiency O 0
might O 0
occur O 0
because O 0
diazepam B-Chemical 0
, O 0
a O 0
gamma B-Chemical 0
- I-Chemical 0
aminobutyric I-Chemical 0
acid I-Chemical 0
- O 0
mimetic O 0
agent O 0
, O 0
was O 0
strikingly O 0
effective O 0
. O 0

This O 0
is O 0
the O 0
first O 0
reported O 0
patient O 0
with O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
probably O 0
caused O 0
by O 0
methylphenidate B-Chemical 0
. O 0

Differential O 0
effects O 0
of O 0
17alpha B-Chemical 0
- I-Chemical 0
ethinylestradiol I-Chemical 0
on O 0
the O 0
neutral O 0
and O 0
acidic O 0
pathways O 0
of O 0
bile B-Chemical 0
salt I-Chemical 0
synthesis O 0
in O 0
the O 0
rat O 0
. O 0

Effects O 0
of O 0
17alpha B-Chemical 0
- I-Chemical 0
ethinylestradiol I-Chemical 0
( O 0
EE B-Chemical 0
) O 0
on O 0
the O 0
neutral O 0
and O 0
acidic O 0
biosynthetic O 0
pathways O 0
of O 0
bile B-Chemical 0
salt I-Chemical 0
( O 0
BS B-Chemical 0
) O 0
synthesis O 0
were O 0
evaluated O 0
in O 0
rats O 0
with O 0
an O 0
intact O 0
enterohepatic O 0
circulation O 0
and O 0
in O 0
rats O 0
with O 0
long O 0
- O 0
term O 0
bile O 0
diversion O 0
to O 0
induce O 0
BS B-Chemical 0
synthesis O 0
. O 0

For O 0
this O 0
purpose O 0
, O 0
bile B-Chemical 0
salt I-Chemical 0
pool O 0
composition O 0
, O 0
synthesis O 0
of O 0
individual O 0
BS B-Chemical 0
in O 0
vivo O 0
, O 0
hepatic O 0
activities O 0
, O 0
and O 0
expression O 0
levels O 0
of O 0
cholesterol B-Chemical 0
7alpha O 0
- O 0
hydroxylase O 0
( O 0
CYP7A O 0
) O 0
, O 0
and O 0
sterol B-Chemical 0
27 O 0
- O 0
hydroxylase O 0
( O 0
CYP27 O 0
) O 0
, O 0
as O 0
well O 0
as O 0
of O 0
other O 0
enzymes O 0
involved O 0
in O 0
BS B-Chemical 0
synthesis O 0
, O 0
were O 0
analyzed O 0
in O 0
rats O 0
treated O 0
with O 0
EE B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
, O 0
3 O 0
days O 0
) O 0
or O 0
its O 0
vehicle O 0
. O 0

BS B-Chemical 0
pool O 0
size O 0
was O 0
decreased O 0
by O 0
27 O 0
% O 0
but O 0
total O 0
BS B-Chemical 0
synthesis O 0
was O 0
not O 0
affected O 0
by O 0
EE B-Chemical 0
in O 0
intact O 0
rats O 0
. O 0

Synthesis O 0
of O 0
cholate B-Chemical 0
was O 0
reduced O 0
by O 0
68 O 0
% O 0
in O 0
EE B-Chemical 0
- O 0
treated O 0
rats O 0
, O 0
while O 0
that O 0
of O 0
chenodeoxycholate B-Chemical 0
was O 0
increased O 0
by O 0
60 O 0
% O 0
. O 0

The O 0
recently O 0
identified O 0
Delta22 O 0
- O 0
isomer O 0
of O 0
beta O 0
- O 0
muricholate O 0
contributed O 0
for O 0
5 O 0
. O 0
4 O 0
% O 0
and O 0
18 O 0
. O 0
3 O 0
% O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
to O 0
the O 0
pool O 0
in O 0
control O 0
and O 0
EE B-Chemical 0
- O 0
treated O 0
rats O 0
, O 0
respectively O 0
, O 0
but O 0
could O 0
not O 0
be O 0
detected O 0
in O 0
bile O 0
after O 0
exhaustion O 0
of O 0
the O 0
pool O 0
. O 0

A O 0
clear O 0
reduction O 0
of O 0
BS B-Chemical 0
synthesis O 0
was O 0
found O 0
in O 0
bile O 0
- O 0
diverted O 0
rats O 0
treated O 0
with O 0
EE B-Chemical 0
, O 0
yet O 0
biliary O 0
BS B-Chemical 0
composition O 0
was O 0
only O 0
minimally O 0
affected O 0
. O 0

Activity O 0
of O 0
CYP7A O 0
was O 0
decreased O 0
by O 0
EE B-Chemical 0
in O 0
both O 0
intact O 0
and O 0
bile O 0
- O 0
diverted O 0
rats O 0
, O 0
whereas O 0
the O 0
activity O 0
of O 0
the O 0
CYP27 O 0
was O 0
not O 0
affected O 0
. O 0

Hepatic O 0
mRNA O 0
levels O 0
of O 0
CYP7A O 0
were O 0
significantly O 0
reduced O 0
by O 0
EE B-Chemical 0
in O 0
bile O 0
- O 0
diverted O 0
rats O 0
only O 0
; O 0
CYP27 O 0
mRNA O 0
levels O 0
were O 0
not O 0
affected O 0
by O 0
EE B-Chemical 0
. O 0

In O 0
addition O 0
, O 0
mRNA O 0
levels O 0
of O 0
sterol B-Chemical 0
12alpha O 0
- O 0
hydroxylase O 0
and O 0
lithocholate O 0
6beta O 0
- O 0
hydroxylase O 0
were O 0
increased O 0
by O 0
bile O 0
diversion O 0
and O 0
suppressed O 0
by O 0
EE B-Chemical 0
. O 0

This O 0
study O 0
shows O 0
that O 0
17alpha B-Chemical 0
- I-Chemical 0
ethinylestradiol I-Chemical 0
( O 0
EE B-Chemical 0
) O 0
- O 0
induced O 0
intrahepatic B-Disease 0
cholestasis I-Disease 0
in O 0
rats O 0
is O 0
associated O 0
with O 0
selective O 0
inhibition O 0
of O 0
the O 0
neutral O 0
pathway O 0
of O 0
bile B-Chemical 0
salt I-Chemical 0
( O 0
BS B-Chemical 0
) O 0
synthesis O 0
. O 0

Simultaneous O 0
impairment O 0
of O 0
other O 0
enzymes O 0
in O 0
the O 0
BS B-Chemical 0
biosynthetic O 0
pathways O 0
may O 0
contribute O 0
to O 0
overall O 0
effects O 0
of O 0
EE B-Chemical 0
on O 0
BS B-Chemical 0
synthesis O 0
. O 0

Glibenclamide B-Chemical 0
- O 0
sensitive O 0
hypotension B-Disease 0
produced O 0
by O 0
helodermin B-Chemical 0
assessed O 0
in O 0
the O 0
rat O 0
. O 0

The O 0
effects O 0
of O 0
helodermin B-Chemical 0
, O 0
a O 0
basic O 0
35 O 0
- O 0
amino B-Chemical 0
acid I-Chemical 0
peptide O 0
isolated O 0
from O 0
the O 0
venom O 0
of O 0
a O 0
lizard O 0
salivary O 0
gland O 0
, O 0
on O 0
arterial O 0
blood O 0
pressure O 0
and O 0
heart O 0
rate O 0
were O 0
examined O 0
in O 0
the O 0
rat O 0
, O 0
focusing O 0
on O 0
the O 0
possibility O 0
that O 0
activation O 0
of O 0
ATP B-Chemical 0
sensitive O 0
K B-Chemical 0
+ O 0
( O 0
K B-Chemical 0
( O 0
ATP B-Chemical 0
) O 0
) O 0
channels O 0
is O 0
involved O 0
in O 0
the O 0
responses O 0
. O 0

The O 0
results O 0
were O 0
also O 0
compared O 0
with O 0
those O 0
of O 0
vasoactive O 0
intestinal O 0
polypeptide O 0
( O 0
VIP O 0
) O 0
. O 0

Helodermin B-Chemical 0
produced O 0
hypotension B-Disease 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
manner O 0
with O 0
approximately O 0
similar O 0
potency O 0
and O 0
duration O 0
to O 0
VIP O 0
. O 0

Hypotension B-Disease 0
induced O 0
by O 0
both O 0
peptides O 0
was O 0
significantly O 0
attenuated O 0
by O 0
glibenclamide B-Chemical 0
, O 0
which O 0
abolished O 0
a O 0
levcromakalim B-Chemical 0
- O 0
produced O 0
decrease O 0
in O 0
arterial O 0
blood O 0
pressure O 0
. O 0

Oxyhemoglobin O 0
did O 0
not O 0
affect O 0
helodermin B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
, O 0
whereas O 0
it O 0
shortened O 0
the O 0
duration O 0
of O 0
acetylcholine B-Chemical 0
( O 0
ACh B-Chemical 0
) O 0
- O 0
produced O 0
hypotension B-Disease 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
helodermin B-Chemical 0
- O 0
produced O 0
hypotension B-Disease 0
is O 0
partly O 0
attributable O 0
to O 0
the O 0
activation O 0
of O 0
glibenclamide B-Chemical 0
- O 0
sensitive O 0
K B-Chemical 0
+ O 0
channels O 0
( O 0
K B-Chemical 0
( O 0
ATP B-Chemical 0
) O 0
channels O 0
) O 0
, O 0
which O 0
presumably O 0
exist O 0
on O 0
arterial O 0
smooth O 0
muscle O 0
cells O 0
. O 0

EDRF O 0
( O 0
endothelium O 0
- O 0
derived O 0
relaxing O 0
factor O 0
) O 0
/ O 0
nitric B-Chemical 0
oxide I-Chemical 0
does O 0
not O 0
seem O 0
to O 0
play O 0
an O 0
important O 0
role O 0
in O 0
the O 0
peptide O 0
- O 0
produced O 0
hypotension B-Disease 0
. O 0

Long O 0
- O 0
term O 0
efficacy O 0
and O 0
adverse O 0
event O 0
of O 0
nifedipine B-Chemical 0
sustained O 0
- O 0
release O 0
tablets O 0
for O 0
cyclosporin B-Chemical 0
A I-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
in O 0
patients O 0
with O 0
psoriasis B-Disease 0
. O 0

Thirteen O 0
psoriatic B-Disease 0
patients O 0
with O 0
hypertension B-Disease 0
during O 0
the O 0
course O 0
of O 0
cyclosporin B-Chemical 0
A I-Chemical 0
therapy O 0
were O 0
treated O 0
for O 0
25 O 0
months O 0
with O 0
a O 0
calcium B-Chemical 0
channel O 0
blocker O 0
, O 0
sustained O 0
- O 0
release O 0
nifedipine B-Chemical 0
, O 0
to O 0
study O 0
the O 0
clinical O 0
antihypertensive O 0
effects O 0
and O 0
adverse O 0
events O 0
during O 0
treatment O 0
with O 0
both O 0
drugs O 0
. O 0

Seven O 0
of O 0
the O 0
13 O 0
patients O 0
had O 0
exhibited O 0
a O 0
subclinical O 0
hypertensive B-Disease 0
state O 0
before O 0
cyclosporin B-Chemical 0
A I-Chemical 0
therapy O 0
. O 0

Both O 0
systolic O 0
and O 0
diastolic O 0
blood O 0
pressures O 0
of O 0
these O 0
13 O 0
patients O 0
were O 0
decreased O 0
significantly O 0
after O 0
4 O 0
weeks O 0
of O 0
nifedipine B-Chemical 0
therapy O 0
, O 0
and O 0
blood O 0
pressure O 0
was O 0
maintained O 0
within O 0
the O 0
normal O 0
range O 0
thereafter O 0
for O 0
25 O 0
months O 0
. O 0

The O 0
adverse O 0
events O 0
during O 0
combined O 0
therapy O 0
with O 0
cyclosporin B-Chemical 0
A I-Chemical 0
and O 0
nifedipine B-Chemical 0
included O 0
an O 0
increase O 0
in O 0
blood B-Chemical 0
urea I-Chemical 0
nitrogen I-Chemical 0
levels O 0
in O 0
9 O 0
of O 0
the O 0
13 O 0
patients O 0
and O 0
development O 0
of O 0
gingival B-Disease 0
hyperplasia I-Disease 0
in O 0
2 O 0
of O 0
the O 0
13 O 0
patients O 0
. O 0

Our O 0
findings O 0
indicate O 0
that O 0
sustained O 0
- O 0
release O 0
nifedipine B-Chemical 0
is O 0
useful O 0
for O 0
hypertensive B-Disease 0
psoriatic B-Disease 0
patients O 0
under O 0
long O 0
- O 0
term O 0
treatment O 0
with O 0
cyclosporin B-Chemical 0
A I-Chemical 0
, O 0
but O 0
that O 0
these O 0
patients O 0
should O 0
be O 0
monitored O 0
for O 0
gingival B-Disease 0
hyperplasia I-Disease 0
. O 0

