22 B-Chemical 0
- I-Chemical 0
oxacalcitriol I-Chemical 0
suppresses O 0
secondary B-Disease 0
hyperparathyroidism I-Disease 0
without O 0
inducing O 0
low B-Disease 0
bone I-Disease 0
turnover I-Disease 0
in O 0
dogs O 0
with O 0
renal B-Disease 0
failure I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Calcitriol B-Chemical 0
therapy O 0
suppresses O 0
serum O 0
levels O 0
of O 0
parathyroid O 0
hormone O 0
( O 0
PTH O 0
) O 0
in O 0
patients O 0
with O 0
renal B-Disease 0
failure I-Disease 0
but O 0
has O 0
several O 0
drawbacks O 0
, O 0
including O 0
hypercalcemia B-Disease 0
and O 0
/ O 0
or O 0
marked O 0
suppression B-Disease 0
of I-Disease 0
bone I-Disease 0
turnover I-Disease 0
, O 0
which O 0
may O 0
lead O 0
to O 0
adynamic B-Disease 0
bone I-Disease 0
disease I-Disease 0
. O 0

A O 0
new O 0
vitamin B-Chemical 0
D I-Chemical 0
analogue O 0
, O 0
22 B-Chemical 0
- I-Chemical 0
oxacalcitriol I-Chemical 0
( O 0
OCT B-Chemical 0
) O 0
, O 0
has O 0
been O 0
shown O 0
to O 0
have O 0
promising O 0
characteristics O 0
. O 0

This O 0
study O 0
was O 0
undertaken O 0
to O 0
determine O 0
the O 0
effects O 0
of O 0
OCT B-Chemical 0
on O 0
serum O 0
PTH O 0
levels O 0
and O 0
bone O 0
turnover O 0
in O 0
states O 0
of O 0
normal O 0
or O 0
impaired B-Disease 0
renal I-Disease 0
function I-Disease 0
. O 0

METHODS O 0
: O 0
Sixty O 0
dogs O 0
were O 0
either O 0
nephrectomized O 0
( O 0
Nx O 0
, O 0
N O 0
= O 0
38 O 0
) O 0
or O 0
sham O 0
- O 0
operated O 0
( O 0
Sham O 0
, O 0
N O 0
= O 0
22 O 0
) O 0
. O 0

The O 0
animals O 0
received O 0
supplemental O 0
phosphate B-Chemical 0
to O 0
enhance O 0
PTH O 0
secretion O 0
. O 0

Fourteen O 0
weeks O 0
after O 0
the O 0
start O 0
of O 0
phosphate B-Chemical 0
supplementation O 0
, O 0
half O 0
of O 0
the O 0
Nx O 0
and O 0
Sham O 0
dogs O 0
received O 0
doses O 0
of O 0
OCT B-Chemical 0
( O 0
three O 0
times O 0
per O 0
week O 0
) O 0
; O 0
the O 0
other O 0
half O 0
were O 0
given O 0
vehicle O 0
for O 0
60 O 0
weeks O 0
. O 0

Thereafter O 0
, O 0
the O 0
treatment O 0
modalities O 0
for O 0
a O 0
subset O 0
of O 0
animals O 0
were O 0
crossed O 0
over O 0
for O 0
an O 0
additional O 0
eight O 0
months O 0
. O 0

Biochemical O 0
and O 0
hormonal O 0
indices O 0
of O 0
calcium B-Chemical 0
and O 0
bone O 0
metabolism O 0
were O 0
measured O 0
throughout O 0
the O 0
study O 0
, O 0
and O 0
bone O 0
biopsies O 0
were O 0
done O 0
at O 0
baseline O 0
, O 0
60 O 0
weeks O 0
after O 0
OCT B-Chemical 0
or O 0
vehicle O 0
treatment O 0
, O 0
and O 0
at O 0
the O 0
end O 0
of O 0
the O 0
crossover O 0
period O 0
. O 0

RESULTS O 0
: O 0
In O 0
Nx O 0
dogs O 0
, O 0
OCT B-Chemical 0
significantly O 0
decreased O 0
serum O 0
PTH O 0
levels O 0
soon O 0
after O 0
the O 0
induction O 0
of O 0
renal B-Disease 0
insufficiency I-Disease 0
. O 0

In O 0
long O 0
- O 0
standing O 0
secondary B-Disease 0
hyperparathyroidism I-Disease 0
, O 0
OCT B-Chemical 0
( O 0
0 O 0
. O 0
03 O 0
microg O 0
/ O 0
kg O 0
) O 0
stabilized O 0
serum O 0
PTH O 0
levels O 0
during O 0
the O 0
first O 0
months O 0
. O 0

Serum O 0
PTH O 0
levels O 0
rose O 0
thereafter O 0
, O 0
but O 0
the O 0
rise O 0
was O 0
less O 0
pronounced O 0
compared O 0
with O 0
baseline O 0
than O 0
the O 0
rise O 0
seen O 0
in O 0
Nx O 0
control O 0
. O 0

These O 0
effects O 0
were O 0
accompanied O 0
by O 0
episodes O 0
of O 0
hypercalcemia B-Disease 0
and O 0
hyperphosphatemia B-Disease 0
. O 0

In O 0
animals O 0
with O 0
normal O 0
renal O 0
function O 0
, O 0
OCT B-Chemical 0
induced O 0
a O 0
transient O 0
decrease O 0
in O 0
serum O 0
PTH O 0
levels O 0
at O 0
a O 0
dose O 0
of O 0
0 O 0
. O 0
1 O 0
microg O 0
/ O 0
kg O 0
, O 0
which O 0
was O 0
not O 0
sustained O 0
with O 0
lowering O 0
of O 0
the O 0
doses O 0
. O 0

In O 0
Nx O 0
dogs O 0
, O 0
OCT B-Chemical 0
reversed O 0
abnormal O 0
bone O 0
formation O 0
, O 0
such O 0
as O 0
woven B-Disease 0
osteoid I-Disease 0
and O 0
fibrosis B-Disease 0
, O 0
but O 0
did O 0
not O 0
significantly O 0
alter O 0
the O 0
level O 0
of O 0
bone O 0
turnover O 0
. O 0

In O 0
addition O 0
, O 0
OCT B-Chemical 0
improved O 0
mineralization O 0
lag O 0
time O 0
, O 0
( O 0
that O 0
is O 0
, O 0
the O 0
rate O 0
at O 0
which O 0
osteoid O 0
mineralizes O 0
) O 0
in O 0
both O 0
Nx O 0
and O 0
Sham O 0
dogs O 0
. O 0

CONCLUSIONS O 0
: O 0
These O 0
results O 0
indicate O 0
that O 0
even O 0
though O 0
OCT B-Chemical 0
does O 0
not O 0
completely O 0
prevent O 0
the O 0
occurrence O 0
of O 0
hypercalcemia B-Disease 0
in O 0
experimental O 0
dogs O 0
with O 0
renal B-Disease 0
insufficiency I-Disease 0
, O 0
it O 0
may O 0
be O 0
of O 0
use O 0
in O 0
the O 0
management O 0
of O 0
secondary B-Disease 0
hyperparathyroidism I-Disease 0
because O 0
it O 0
does O 0
not O 0
induce O 0
low B-Disease 0
bone I-Disease 0
turnover I-Disease 0
and O 0
, O 0
therefore O 0
, O 0
does O 0
not O 0
increase O 0
the O 0
risk O 0
of O 0
adynamic B-Disease 0
bone I-Disease 0
disease I-Disease 0
. O 0

Hypotension B-Disease 0
, O 0
bradycardia B-Disease 0
, O 0
and O 0
asystole B-Disease 0
after O 0
high O 0
- O 0
dose O 0
intravenous O 0
methylprednisolone B-Chemical 0
in O 0
a O 0
monitored O 0
patient O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
hypotension B-Disease 0
, O 0
bradycardia B-Disease 0
, O 0
and O 0
asystole B-Disease 0
after O 0
intravenous O 0
administration O 0
of O 0
high O 0
- O 0
dose O 0
methylprednisolone B-Chemical 0
in O 0
a O 0
73 O 0
- O 0
year O 0
- O 0
old O 0
patient O 0
who O 0
underwent O 0
electrocardiographic O 0
( O 0
ECG O 0
) O 0
monitoring O 0
throughout O 0
the O 0
episode O 0
. O 0

There O 0
was O 0
a O 0
history O 0
of O 0
ischemic B-Disease 0
cardiac B-Disease 0
disease I-Disease 0
9 O 0
years O 0
earlier O 0
. O 0

The O 0
patient O 0
was O 0
admitted O 0
with O 0
a O 0
pulmonary B-Disease 0
- I-Disease 0
renal I-Disease 0
syndrome I-Disease 0
with O 0
hemoptysis B-Disease 0
, O 0
rapidly O 0
progressive O 0
renal B-Disease 0
failure I-Disease 0
, O 0
and O 0
hypoxemia B-Disease 0
that O 0
required O 0
mechanical O 0
ventilation O 0
in O 0
the O 0
intensive O 0
care O 0
unit O 0
. O 0

After O 0
receiving O 0
advanced O 0
cardiopulmonary O 0
resuscitation O 0
, O 0
the O 0
patient O 0
recovered O 0
cardiac O 0
rhythm O 0
. O 0

The O 0
ECG O 0
showed O 0
a O 0
junctional O 0
rhythm O 0
without O 0
ventricular B-Disease 0
arrhythmia I-Disease 0
. O 0

This O 0
study O 0
reviews O 0
the O 0
current O 0
proposed O 0
mechanisms O 0
of O 0
sudden B-Disease 0
death I-Disease 0
after O 0
a O 0
high O 0
dose O 0
of O 0
intravenous O 0
methylprednisolone B-Chemical 0
( O 0
IVMP B-Chemical 0
) O 0
. O 0

These O 0
mechanisms O 0
are O 0
not O 0
well O 0
understood O 0
because O 0
, O 0
in O 0
most O 0
cases O 0
, O 0
the O 0
patients O 0
were O 0
not O 0
monitored O 0
at O 0
the O 0
moment O 0
of O 0
the O 0
event O 0
. O 0

Rapid O 0
infusion O 0
and O 0
underlying O 0
cardiac B-Disease 0
disease I-Disease 0
were O 0
important O 0
risk O 0
factors O 0
in O 0
the O 0
case O 0
reported O 0
here O 0
, O 0
and O 0
the O 0
authors O 0
discount O 0
ventricular B-Disease 0
arrhythmia I-Disease 0
as O 0
the O 0
main O 0
mechanism O 0
. O 0

Worsening O 0
of O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
by O 0
motor O 0
and O 0
mental O 0
tasks O 0
. O 0

Ten O 0
patients O 0
who O 0
had O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
with O 0
disabling O 0
dyskinesia B-Disease 0
were O 0
included O 0
in O 0
this O 0
study O 0
to O 0
evaluate O 0
the O 0
role O 0
of O 0
mental O 0
( O 0
mental O 0
calculation O 0
) O 0
and O 0
motor O 0
( O 0
flexion O 0
/ O 0
extension O 0
of O 0
right O 0
fingers O 0
, O 0
flexion O 0
/ O 0
extension O 0
of O 0
left O 0
fingers O 0
, O 0
flexion O 0
/ O 0
extension O 0
of O 0
the O 0
neck O 0
, O 0
speaking O 0
aloud O 0
) O 0
tasks O 0
on O 0
the O 0
worsening O 0
of O 0
peak O 0
- O 0
dose O 0
dyskinesia B-Disease 0
following O 0
administration O 0
of O 0
an O 0
effective O 0
single O 0
dose O 0
of O 0
apomorphine B-Chemical 0
. O 0

Compared O 0
with O 0
the O 0
score O 0
at O 0
rest O 0
( O 0
1 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
3 O 0
) O 0
, O 0
a O 0
significant O 0
aggravation O 0
of O 0
the O 0
dyskinesia B-Disease 0
score O 0
was O 0
observed O 0
during O 0
speaking O 0
aloud O 0
( O 0
5 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
1 O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
, O 0
movements O 0
of O 0
right O 0
( O 0
4 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
0 O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
and O 0
left O 0
( O 0
3 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
8 O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
fingers O 0
, O 0
movements O 0
of O 0
the O 0
neck O 0
( O 0
5 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
0 O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
, O 0
and O 0
mental O 0
calculation O 0
( O 0
3 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
0 O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
activation O 0
tasks O 0
such O 0
as O 0
" O 0
speaking O 0
aloud O 0
" O 0
could O 0
be O 0
used O 0
for O 0
objective O 0
assessment O 0
of O 0
dyskinesia B-Disease 0
severity O 0
. O 0

Urine 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
- O 0
a O 0
marker O 0
of O 0
tubular O 0
damage O 0
? O 0

BACKGROUND O 0
: O 0
Although O 0
an O 0
indicator O 0
of O 0
renal B-Disease 0
tubular I-Disease 0
dysfunction I-Disease 0
, O 0
an O 0
increased 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
activity O 0
might O 0
reflect O 0
increased O 0
lysosomal O 0
activity O 0
in O 0
renal O 0
tubular O 0
cells O 0
. O 0

METHODS O 0
: O 0
Puromycin B-Chemical 0
aminonucleoside I-Chemical 0
( O 0
PAN B-Chemical 0
) O 0
was O 0
administered O 0
to O 0
Sprague O 0
Dawley O 0
rats O 0
to O 0
induce O 0
proteinuria B-Disease 0
. O 0

Total O 0
protein O 0
, O 0
albumin O 0
, O 0
NAG O 0
activity O 0
and O 0
protein O 0
electrophoretic O 0
pattern O 0
were O 0
assessed O 0
in O 0
daily O 0
urine O 0
samples O 0
for O 0
33 O 0
days O 0
. O 0

The O 0
morphological O 0
appearance O 0
of O 0
the O 0
kidneys O 0
was O 0
examined O 0
on O 0
days O 0
three O 0
, O 0
four O 0
, O 0
six O 0
, O 0
eight O 0
and O 0
thirty O 0
three O 0
and O 0
the O 0
NAG O 0
isoenzyme O 0
patterns O 0
on O 0
days O 0
zero O 0
, O 0
four O 0
, O 0
eight O 0
and O 0
thirty O 0
three O 0
. O 0

RESULTS O 0
: O 0
Following O 0
intravenous O 0
PAN B-Chemical 0
urine O 0
volume O 0
and O 0
urine O 0
NAG O 0
activity O 0
increased O 0
significantly O 0
by O 0
day O 0
two O 0
, O 0
but O 0
returned O 0
to O 0
normal O 0
by O 0
day O 0
four O 0
. O 0

After O 0
day O 0
four O 0
all O 0
treated O 0
animals O 0
exhibited O 0
a O 0
marked O 0
rise O 0
in O 0
urine O 0
albumin O 0
, O 0
total O 0
protein O 0
excretion O 0
and O 0
NAG O 0
activity O 0
. O 0

Electrophoresis O 0
showed O 0
a O 0
generalised O 0
increase O 0
in O 0
middle O 0
and O 0
high O 0
molecular O 0
weight O 0
urine O 0
proteins O 0
from O 0
day O 0
four O 0
onwards O 0
. O 0

Protein O 0
droplets O 0
first O 0
appeared O 0
prominent O 0
in O 0
tubular O 0
cells O 0
on O 0
day O 0
four O 0
. O 0

Peak O 0
urine O 0
NAG O 0
activity O 0
and O 0
a O 0
change O 0
in O 0
NAG O 0
isoenzyme O 0
pattern O 0
coincided O 0
with O 0
both O 0
the O 0
peak O 0
proteinuria B-Disease 0
and O 0
the O 0
reduction O 0
in O 0
intracellular O 0
protein O 0
and O 0
NAG O 0
droplets O 0
( O 0
day O 0
six O 0
onwards O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
This O 0
animal O 0
model O 0
demonstrates O 0
that O 0
an O 0
increase O 0
in O 0
lysosomal O 0
turnover O 0
and O 0
hence O 0
urine O 0
NAG O 0
activity O 0
, O 0
occurs O 0
when O 0
increased O 0
protein O 0
is O 0
presented O 0
to O 0
the O 0
tubular O 0
cells O 0
. O 0

Urine O 0
NAG O 0
activity O 0
is O 0
thus O 0
a O 0
measure O 0
of O 0
altered O 0
function O 0
in O 0
the O 0
renal O 0
tubules O 0
and O 0
not O 0
simply O 0
an O 0
indicator O 0
of O 0
damage O 0
. O 0

Cauda B-Disease 0
equina I-Disease 0
syndrome I-Disease 0
after O 0
spinal O 0
anaesthesia O 0
with O 0
hyperbaric O 0
5 O 0
% O 0
lignocaine B-Chemical 0
: O 0
a O 0
review O 0
of O 0
six O 0
cases O 0
of O 0
cauda B-Disease 0
equina I-Disease 0
syndrome I-Disease 0
reported O 0
to O 0
the O 0
Swedish O 0
Pharmaceutical O 0
Insurance O 0
1993 O 0
- O 0
1997 O 0
. O 0

Six O 0
cases O 0
of O 0
cauda B-Disease 0
equina I-Disease 0
syndrome I-Disease 0
with O 0
varying O 0
severity O 0
were O 0
reported O 0
to O 0
the O 0
Swedish O 0
Pharmaceutical O 0
Insurance O 0
during O 0
the O 0
period O 0
1993 O 0
- O 0
1997 O 0
. O 0

All O 0
were O 0
associated O 0
with O 0
spinal O 0
anaesthesia O 0
using O 0
hyperbaric O 0
5 O 0
% O 0
lignocaine B-Chemical 0
. O 0

Five O 0
cases O 0
had O 0
single O 0
- O 0
shot O 0
spinal O 0
anaesthesia O 0
and O 0
one O 0
had O 0
a O 0
repeat O 0
spinal O 0
anaesthetic O 0
due O 0
to O 0
inadequate O 0
block O 0
. O 0

The O 0
dose O 0
of O 0
hyperbaric O 0
5 O 0
% O 0
lignocaine B-Chemical 0
administered O 0
ranged O 0
from O 0
60 O 0
to O 0
120 O 0
mg O 0
. O 0

Three O 0
of O 0
the O 0
cases O 0
were O 0
most O 0
likely O 0
caused O 0
by O 0
direct O 0
neurotoxicity B-Disease 0
of O 0
hyperbaric O 0
5 O 0
% O 0
lignocaine B-Chemical 0
. O 0

In O 0
the O 0
other O 0
3 O 0
cases O 0
, O 0
direct O 0
neurotoxicity B-Disease 0
was O 0
also O 0
probable O 0
, O 0
but O 0
unfortunately O 0
radiological O 0
investigations O 0
were O 0
not O 0
done O 0
to O 0
definitely O 0
exclude O 0
a O 0
compressive O 0
aetiology O 0
. O 0

All O 0
cases O 0
sustained O 0
permanent O 0
neurological B-Disease 0
deficits I-Disease 0
. O 0

We O 0
recommend O 0
that O 0
hyperbaric O 0
lignocaine B-Chemical 0
should O 0
be O 0
administered O 0
in O 0
concentrations O 0
not O 0
greater O 0
than O 0
2 O 0
% O 0
and O 0
at O 0
a O 0
total O 0
dose O 0
preferably O 0
not O 0
exceeding O 0
60 O 0
mg O 0
. O 0

Systemic O 0
toxicity B-Disease 0
following O 0
administration O 0
of O 0
sirolimus B-Chemical 0
( O 0
formerly O 0
rapamycin B-Chemical 0
) O 0
for O 0
psoriasis B-Disease 0
: O 0
association O 0
of O 0
capillary B-Disease 0
leak I-Disease 0
syndrome I-Disease 0
with O 0
apoptosis O 0
of O 0
lesional O 0
lymphocytes O 0
. O 0

BACKGROUND O 0
: O 0
Sirolimus B-Chemical 0
( O 0
formerly O 0
rapamycin B-Chemical 0
) O 0
is O 0
an O 0
immunosuppressive O 0
agent O 0
that O 0
interferes O 0
with O 0
T O 0
- O 0
cell O 0
activation O 0
. O 0

After O 0
2 O 0
individuals O 0
with O 0
psoriasis B-Disease 0
developed O 0
a O 0
capillary B-Disease 0
leak I-Disease 0
syndrome I-Disease 0
following O 0
treatment O 0
with O 0
oral O 0
sirolimus B-Chemical 0
lesional O 0
skin O 0
cells O 0
and O 0
activated O 0
peripheral O 0
blood O 0
cells O 0
were O 0
analyzed O 0
for O 0
induction O 0
of O 0
apoptosis O 0
. O 0

OBSERVATIONS O 0
: O 0
A O 0
keratome O 0
skin O 0
specimen O 0
from O 0
1 O 0
patient O 0
with O 0
sirolimus B-Chemical 0
- O 0
induced O 0
capillary B-Disease 0
leak I-Disease 0
syndrome I-Disease 0
had O 0
a O 0
2 O 0
. O 0
3 O 0
- O 0
fold O 0
increase O 0
in O 0
percentage O 0
of O 0
apoptotic O 0
cells O 0
( O 0
to O 0
48 O 0
% O 0
) O 0
compared O 0
with O 0
an O 0
unaffected O 0
sirolimus B-Chemical 0
- O 0
treated O 0
patient O 0
with O 0
psoriasis B-Disease 0
( O 0
21 O 0
% O 0
) O 0
. O 0

Activated O 0
peripheral O 0
blood O 0
T O 0
cells O 0
from O 0
patients O 0
with O 0
psoriasis B-Disease 0
tended O 0
to O 0
exhibit O 0
greater O 0
spontaneous O 0
or O 0
dexamethasone B-Chemical 0
- O 0
induced O 0
apoptosis O 0
than O 0
did O 0
normal O 0
T O 0
cells O 0
, O 0
particularly O 0
in O 0
the O 0
presence O 0
of O 0
sirolimus B-Chemical 0
. O 0

CONCLUSIONS O 0
: O 0
Severe O 0
adverse O 0
effects O 0
of O 0
sirolimus B-Chemical 0
include O 0
fever B-Disease 0
, O 0
anemia B-Disease 0
, O 0
and O 0
capillary B-Disease 0
leak I-Disease 0
syndrome I-Disease 0
. O 0

These O 0
symptoms O 0
may O 0
be O 0
the O 0
result O 0
of O 0
drug O 0
- O 0
induced O 0
apoptosis O 0
of O 0
lesional O 0
leukocytes O 0
, O 0
especially O 0
activated O 0
T O 0
lymphocytes O 0
, O 0
and O 0
possibly O 0
release O 0
of O 0
inflammatory O 0
mediators O 0
. O 0

Because O 0
patients O 0
with O 0
severe O 0
psoriasis B-Disease 0
may O 0
develop O 0
capillary B-Disease 0
leak I-Disease 0
from O 0
various O 0
systemic O 0
therapies O 0
, O 0
clinical O 0
monitoring O 0
is O 0
advisable O 0
for O 0
patients O 0
with O 0
inflammatory B-Disease 0
diseases I-Disease 0
who O 0
are O 0
treated O 0
with O 0
immune O 0
modulators O 0
. O 0

Effect O 0
of O 0
lithium B-Chemical 0
maintenance O 0
therapy O 0
on O 0
thyroid O 0
and O 0
parathyroid O 0
function O 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
assess O 0
changes O 0
induced O 0
by O 0
lithium B-Chemical 0
maintenance O 0
therapy O 0
on O 0
the O 0
incidence O 0
of O 0
thyroid O 0
, O 0
parathyroid O 0
and O 0
ion O 0
alterations O 0
. O 0

These O 0
were O 0
evaluated O 0
with O 0
respect O 0
to O 0
the O 0
duration O 0
of O 0
lithium B-Chemical 0
therapy O 0
, O 0
age O 0
, O 0
sex O 0
, O 0
and O 0
family O 0
history O 0
( O 0
whether O 0
or O 0
not O 0
the O 0
patient O 0
had O 0
a O 0
first O 0
- O 0
degree O 0
relative O 0
with O 0
thyroid B-Disease 0
disease I-Disease 0
) O 0
. O 0

DESIGN O 0
: O 0
Prospective O 0
study O 0
. O 0

SETTING O 0
: O 0
Affective O 0
Disorders O 0
Clinic O 0
at O 0
St O 0
. O 0

Mary O 0
' O 0
s O 0
Hospital O 0
, O 0
Montreal O 0
. O 0

PATIENTS O 0
: O 0
One O 0
hundred O 0
and O 0
one O 0
patients O 0
( O 0
28 O 0
men O 0
and O 0
73 O 0
women O 0
) O 0
with O 0
bipolar B-Disease 0
disorder I-Disease 0
receiving O 0
lithium B-Chemical 0
maintenance O 0
therapy O 0
ranging O 0
from O 0
1 O 0
year O 0
' O 0
s O 0
to O 0
32 O 0
years O 0
' O 0
duration O 0
. O 0

The O 0
control O 0
group O 0
consisted O 0
of O 0
82 O 0
patients O 0
with O 0
no O 0
psychiatric B-Disease 0
or O 0
endocrinological O 0
diagnoses O 0
from O 0
the O 0
hospital O 0
' O 0
s O 0
out O 0
- O 0
patient O 0
clinics O 0
. O 0

OUTCOME O 0
MEASURES O 0
: O 0
Laboratory O 0
analyses O 0
of O 0
calcium B-Chemical 0
, O 0
magnesium B-Chemical 0
and O 0
thyroid O 0
- O 0
stimulating O 0
hormone O 0
levels O 0
performed O 0
before O 0
beginning O 0
lithium B-Chemical 0
therapy O 0
and O 0
at O 0
biannual O 0
follow O 0
- O 0
up O 0
. O 0

RESULTS O 0
: O 0
Hypothyroidism B-Disease 0
developed O 0
in O 0
40 O 0
patients O 0
, O 0
excluding O 0
8 O 0
patients O 0
who O 0
were O 0
hypothyroid B-Disease 0
at O 0
baseline O 0
. O 0

All O 0
patients O 0
having O 0
first O 0
- O 0
degree O 0
relatives O 0
affected O 0
by O 0
thyroid B-Disease 0
illness I-Disease 0
had O 0
accelerated O 0
onset O 0
of O 0
hypothyroidism B-Disease 0
( O 0
3 O 0
. O 0
7 O 0
years O 0
after O 0
onset O 0
of O 0
lithium B-Chemical 0
therapy O 0
) O 0
compared O 0
with O 0
patients O 0
without O 0
a O 0
family O 0
history O 0
( O 0
8 O 0
. O 0
6 O 0
years O 0
after O 0
onset O 0
of O 0
lithium B-Chemical 0
therapy O 0
) O 0
. O 0

Women O 0
over O 0
60 O 0
years O 0
of O 0
age O 0
were O 0
more O 0
often O 0
affected O 0
by O 0
hypothyroidism B-Disease 0
than O 0
women O 0
under O 0
60 O 0
years O 0
of O 0
age O 0
( O 0
34 O 0
. O 0
6 O 0
% O 0
versus O 0
31 O 0
. O 0
9 O 0
% O 0
) O 0
. O 0

Magnesium B-Chemical 0
levels O 0
in O 0
patients O 0
on O 0
lithium B-Chemical 0
treatment O 0
were O 0
unchanged O 0
from O 0
baseline O 0
levels O 0
. O 0

After O 0
lithium B-Chemical 0
treatment O 0
, O 0
calcium B-Chemical 0
levels O 0
were O 0
higher O 0
than O 0
either O 0
baseline O 0
levels O 0
or O 0
control O 0
levels O 0
. O 0

Thus O 0
, O 0
lithium B-Chemical 0
treatment O 0
counteracted O 0
the O 0
decrease O 0
in O 0
plasma O 0
calcium B-Chemical 0
levels O 0
associated O 0
with O 0
aging O 0
. O 0

CONCLUSIONS O 0
: O 0
Familial O 0
thyroid B-Disease 0
illness I-Disease 0
is O 0
a O 0
risk O 0
factor O 0
for O 0
hypothyroidism B-Disease 0
and O 0
hypercalcemia B-Disease 0
during O 0
lithium B-Chemical 0
therapy O 0
. O 0

Severe O 0
immune O 0
hemolytic B-Disease 0
anemia I-Disease 0
associated O 0
with O 0
prophylactic O 0
use O 0
of O 0
cefotetan B-Chemical 0
in O 0
obstetric O 0
and O 0
gynecologic O 0
procedures O 0
. O 0

Second O 0
- O 0
and O 0
third O 0
- O 0
generation O 0
cephalosporins B-Chemical 0
, O 0
especially O 0
cefotetan B-Chemical 0
, O 0
are O 0
increasingly O 0
associated O 0
with O 0
severe O 0
, O 0
sometimes O 0
fatal O 0
immune O 0
hemolytic B-Disease 0
anemia I-Disease 0
. O 0

We O 0
noticed O 0
that O 0
10 O 0
of O 0
our O 0
35 O 0
cases O 0
of O 0
cefotetan B-Chemical 0
- O 0
induced O 0
hemolytic B-Disease 0
anemias I-Disease 0
were O 0
in O 0
patients O 0
who O 0
had O 0
received O 0
cefotetan B-Chemical 0
prophylactically O 0
for O 0
obstetric O 0
and O 0
gynecologic O 0
procedures O 0
. O 0

Eight O 0
of O 0
these O 0
cases O 0
of O 0
severe O 0
immune O 0
hemolytic B-Disease 0
anemia I-Disease 0
are O 0
described O 0
. O 0

Effects O 0
of O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
on O 0
hemostasis O 0
in O 0
patients O 0
with O 0
aneurysmal B-Disease 0
subarachnoid I-Disease 0
hemorrhage I-Disease 0
. O 0

Platelet O 0
function O 0
is O 0
impaired O 0
by O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
( O 0
NSAIDs O 0
) O 0
with O 0
prominent O 0
anti O 0
- O 0
inflammatory O 0
properties O 0
. O 0

Their O 0
safety O 0
in O 0
patients O 0
undergoing O 0
intracranial O 0
surgery O 0
is O 0
under O 0
debate O 0
. O 0

Patients O 0
with O 0
aneurysmal B-Disease 0
subarachnoid I-Disease 0
hemorrhage I-Disease 0
( O 0
SAH B-Disease 0
) O 0
were O 0
randomized O 0
to O 0
receive O 0
either O 0
ketoprofen B-Chemical 0
, O 0
100 O 0
mg O 0
, O 0
three O 0
times O 0
a O 0
day O 0
( O 0
ketoprofen B-Chemical 0
group O 0
, O 0
n O 0
= O 0
9 O 0
) O 0
or O 0
a O 0
weak O 0
NSAID O 0
, O 0
acetaminophen B-Chemical 0
, O 0
1 O 0
g O 0
, O 0
three O 0
times O 0
a O 0
day O 0
( O 0
acetaminophen B-Chemical 0
group O 0
, O 0
n O 0
= O 0
9 O 0
) O 0
starting O 0
immediately O 0
after O 0
the O 0
diagnosis O 0
of O 0
aneurysmal B-Disease 0
SAH B-Disease 0
. O 0

Treatment O 0
was O 0
continued O 0
for O 0
3 O 0
days O 0
postoperatively O 0
. O 0

Test O 0
blood O 0
samples O 0
were O 0
taken O 0
before O 0
treatment O 0
and O 0
surgery O 0
as O 0
well O 0
as O 0
on O 0
the O 0
first O 0
, O 0
third O 0
, O 0
and O 0
fifth O 0
postoperative O 0
mornings O 0
. O 0

Maximal O 0
platelet B-Disease 0
aggregation I-Disease 0
induced O 0
by O 0
6 O 0
microM O 0
of O 0
adenosine B-Chemical 0
diphosphate I-Chemical 0
decreased O 0
after O 0
administration O 0
of O 0
ketoprofen B-Chemical 0
. O 0

Aggregation O 0
was O 0
lower O 0
( O 0
P O 0
< O 0
. O 0
05 O 0
) O 0
in O 0
the O 0
ketoprofen B-Chemical 0
group O 0
than O 0
in O 0
the O 0
acetaminophen B-Chemical 0
group O 0
just O 0
before O 0
surgery O 0
and O 0
on O 0
the O 0
third O 0
postoperative O 0
day O 0
. O 0

In O 0
contrast O 0
, O 0
maximal O 0
platelet B-Disease 0
aggregation I-Disease 0
increased O 0
in O 0
the O 0
acetaminophen B-Chemical 0
group O 0
on O 0
the O 0
third O 0
postoperative O 0
day O 0
as O 0
compared O 0
with O 0
the O 0
pretreatment O 0
platelet B-Disease 0
aggregation I-Disease 0
results O 0
( O 0
P O 0
< O 0
. O 0
05 O 0
) O 0
. O 0

One O 0
patient O 0
in O 0
the O 0
ketoprofen B-Chemical 0
group O 0
developed O 0
a O 0
postoperative O 0
intracranial O 0
hematoma B-Disease 0
. O 0

Coagulation O 0
( O 0
prothrombin O 0
time O 0
[ O 0
PT O 0
] O 0
, O 0
activated O 0
partial O 0
thromboplastin O 0
time O 0
[ O 0
APPT O 0
] O 0
, O 0
fibrinogen O 0
concentration O 0
, O 0
and O 0
antithrombin O 0
III O 0
[ O 0
AT O 0
III O 0
] O 0
) O 0
was O 0
comparable O 0
between O 0
the O 0
two O 0
groups O 0
. O 0

Ketoprofen B-Chemical 0
but O 0
not O 0
acetaminophen B-Chemical 0
impaired O 0
platelet O 0
function O 0
in O 0
patients O 0
with O 0
SAH B-Disease 0
. O 0

If O 0
ketoprofen B-Chemical 0
is O 0
used O 0
before O 0
surgery O 0
on O 0
cerebral O 0
artery B-Disease 0
aneurysms I-Disease 0
, O 0
it O 0
may O 0
pose O 0
an O 0
additional O 0
risk O 0
factor O 0
for O 0
hemorrhage B-Disease 0
. O 0

Nitric B-Chemical 0
oxide I-Chemical 0
synthase O 0
expression O 0
in O 0
the O 0
course O 0
of O 0
lead B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
. O 0

We O 0
recently O 0
showed O 0
elevated O 0
reactive O 0
oxygen B-Chemical 0
species O 0
( O 0
ROS O 0
) O 0
, O 0
reduced O 0
urinary O 0
excretion O 0
of O 0
NO B-Chemical 0
metabolites O 0
( O 0
NOx O 0
) O 0
, O 0
and O 0
increased O 0
NO B-Chemical 0
sequestration O 0
as O 0
nitrotyrosine B-Chemical 0
in O 0
various O 0
tissues O 0
in O 0
rats O 0
with O 0
lead B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
. O 0

This O 0
study O 0
was O 0
designed O 0
to O 0
discern O 0
whether O 0
the O 0
reduction O 0
in O 0
urinary O 0
NOx O 0
in O 0
lead B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
is O 0
, O 0
in O 0
part O 0
, O 0
due O 0
to O 0
depressed O 0
NO B-Chemical 0
synthase O 0
( O 0
NOS O 0
) O 0
expression O 0
. O 0

Male O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
were O 0
randomly O 0
assigned O 0
to O 0
a O 0
lead B-Chemical 0
- O 0
treated O 0
group O 0
( O 0
given O 0
lead B-Chemical 0
acetate I-Chemical 0
, O 0
100 O 0
ppm O 0
, O 0
in O 0
drinking O 0
water O 0
and O 0
regular O 0
rat O 0
chow O 0
) O 0
, O 0
a O 0
group O 0
given O 0
lead B-Chemical 0
and O 0
vitamin B-Chemical 0
E I-Chemical 0
- O 0
fortified O 0
chow O 0
, O 0
or O 0
a O 0
normal O 0
control O 0
group O 0
given O 0
either O 0
regular O 0
food O 0
and O 0
water O 0
or O 0
vitamin B-Chemical 0
E I-Chemical 0
- O 0
fortified O 0
food O 0
for O 0
12 O 0
weeks O 0
. O 0

Tail O 0
blood O 0
pressure O 0
, O 0
urinary O 0
NOx O 0
excretion O 0
, O 0
plasma O 0
malondialdehyde B-Chemical 0
( O 0
MDA B-Chemical 0
) O 0
, O 0
and O 0
endothelial O 0
and O 0
inducible O 0
NOS O 0
( O 0
eNOS O 0
and O 0
iNOS O 0
) O 0
isotypes O 0
in O 0
the O 0
aorta O 0
and O 0
kidney O 0
were O 0
measured O 0
. O 0

The O 0
lead B-Chemical 0
- O 0
treated O 0
group O 0
exhibited O 0
a O 0
rise O 0
in O 0
blood O 0
pressure O 0
and O 0
plasma O 0
MDA B-Chemical 0
concentration O 0
, O 0
a O 0
fall O 0
in O 0
urinary O 0
NOx O 0
excretion O 0
, O 0
and O 0
a O 0
paradoxical O 0
rise O 0
in O 0
vascular O 0
and O 0
renal O 0
tissue O 0
eNOS O 0
and O 0
iNOS O 0
expression O 0
. O 0

Vitamin B-Chemical 0
E I-Chemical 0
supplementation O 0
ameliorated O 0
hypertension B-Disease 0
, O 0
lowered O 0
plasma O 0
MDA B-Chemical 0
concentration O 0
, O 0
and O 0
raised O 0
urinary O 0
NOx O 0
excretion O 0
while O 0
significantly O 0
lowering O 0
vascular O 0
, O 0
but O 0
not O 0
renal O 0
, O 0
tissue O 0
eNOS O 0
and O 0
iNOS O 0
expression O 0
. O 0

Vitamin B-Chemical 0
E I-Chemical 0
supplementation O 0
had O 0
no O 0
effect O 0
on O 0
either O 0
blood O 0
pressure O 0
, O 0
plasma O 0
MDA B-Chemical 0
, O 0
or O 0
NOS O 0
expression O 0
in O 0
the O 0
control O 0
group O 0
. O 0

The O 0
study O 0
also O 0
revealed O 0
significant O 0
inhibition O 0
of O 0
NOS O 0
enzymatic O 0
activity O 0
by O 0
lead B-Chemical 0
in O 0
cell O 0
- O 0
free O 0
preparations O 0
. O 0

In O 0
conclusion O 0
, O 0
lead B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
in O 0
this O 0
model O 0
was O 0
associated O 0
with O 0
a O 0
compensatory O 0
upregulation O 0
of O 0
renal O 0
and O 0
vascular O 0
eNOS O 0
and O 0
iNOS O 0
expression O 0
. O 0

This O 0
is O 0
, O 0
in O 0
part O 0
, O 0
due O 0
to O 0
ROS O 0
- O 0
mediated O 0
NO B-Chemical 0
inactivation O 0
, O 0
lead B-Chemical 0
- O 0
associated O 0
inhibition O 0
of O 0
NOS O 0
activity O 0
, O 0
and O 0
perhaps O 0
stimulatory O 0
actions O 0
of O 0
increased O 0
shear O 0
stress O 0
associated O 0
with O 0
hypertension B-Disease 0
. O 0

Glyceryl B-Chemical 0
trinitrate I-Chemical 0
induces O 0
attacks O 0
of O 0
migraine B-Disease 0
without I-Disease 0
aura I-Disease 0
in O 0
sufferers O 0
of O 0
migraine B-Disease 0
with I-Disease 0
aura I-Disease 0
. O 0

Migraine B-Disease 0
with I-Disease 0
aura I-Disease 0
and O 0
migraine B-Disease 0
without I-Disease 0
aura I-Disease 0
have O 0
the O 0
same O 0
pain B-Disease 0
phase O 0
, O 0
thus O 0
indicating O 0
that O 0
migraine B-Disease 0
with I-Disease 0
aura I-Disease 0
and O 0
migraine B-Disease 0
without I-Disease 0
aura I-Disease 0
share O 0
a O 0
common O 0
pathway O 0
of O 0
nociception O 0
. O 0

In O 0
recent O 0
years O 0
, O 0
increasing O 0
evidence O 0
has O 0
suggested O 0
that O 0
the O 0
messenger O 0
molecule O 0
nitric B-Chemical 0
oxide I-Chemical 0
( O 0
NO B-Chemical 0
) O 0
is O 0
involved O 0
in O 0
pain B-Disease 0
mechanisms O 0
of O 0
migraine B-Disease 0
without I-Disease 0
aura I-Disease 0
. O 0

In O 0
order O 0
to O 0
clarify O 0
whether O 0
the O 0
same O 0
is O 0
true O 0
for O 0
migraine B-Disease 0
with I-Disease 0
aura I-Disease 0
, O 0
in O 0
the O 0
present O 0
study O 0
we O 0
examined O 0
the O 0
headache B-Disease 0
response O 0
to O 0
intravenous O 0
infusion O 0
of O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
( O 0
GTN B-Chemical 0
) O 0
( O 0
0 O 0
. O 0
5 O 0
microg O 0
/ O 0
kg O 0
/ O 0
min O 0
for O 0
20 O 0
min O 0
) O 0
in O 0
12 O 0
sufferers O 0
of O 0
migraine B-Disease 0
with I-Disease 0
aura I-Disease 0
. O 0

The O 0
specific O 0
aim O 0
was O 0
to O 0
elucidate O 0
whether O 0
an O 0
aura O 0
and O 0
/ O 0
or O 0
an O 0
attack O 0
of O 0
migraine B-Disease 0
without I-Disease 0
aura I-Disease 0
could O 0
be O 0
induced O 0
. O 0

Fourteen O 0
healthy O 0
subjects O 0
served O 0
as O 0
controls O 0
. O 0

Aura O 0
symptoms O 0
were O 0
not O 0
elicited O 0
in O 0
any O 0
subject O 0
. O 0

Headache B-Disease 0
was O 0
more O 0
severe O 0
in O 0
migraineurs B-Disease 0
than O 0
in O 0
the O 0
controls O 0
during O 0
and O 0
immediately O 0
after O 0
GTN B-Chemical 0
infusion O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
037 O 0
) O 0
as O 0
well O 0
as O 0
during O 0
the O 0
following O 0
11 O 0
h O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
008 O 0
) O 0
. O 0

In O 0
the O 0
controls O 0
, O 0
the O 0
GTN B-Chemical 0
- O 0
induced O 0
headache B-Disease 0
gradually O 0
disappeared O 0
, O 0
whereas O 0
in O 0
migraineurs B-Disease 0
peak O 0
headache B-Disease 0
intensity O 0
occurred O 0
at O 0
a O 0
mean O 0
time O 0
of O 0
240 O 0
min O 0
post O 0
- O 0
infusion O 0
. O 0

At O 0
this O 0
time O 0
the O 0
induced O 0
headache B-Disease 0
in O 0
6 O 0
of O 0
12 O 0
migraineurs B-Disease 0
fulfilled O 0
the O 0
diagnostic O 0
criteria O 0
for O 0
migraine B-Disease 0
without I-Disease 0
aura I-Disease 0
of O 0
the O 0
International O 0
Headache B-Disease 0
Society O 0
. O 0

The O 0
results O 0
therefore O 0
suggest O 0
that O 0
NO B-Chemical 0
is O 0
involved O 0
in O 0
the O 0
pain B-Disease 0
mechanisms O 0
of O 0
migraine B-Disease 0
with I-Disease 0
aura I-Disease 0
. O 0

Since O 0
cortical O 0
spreading O 0
depression B-Disease 0
has O 0
been O 0
shown O 0
to O 0
liberate O 0
NO B-Chemical 0
in O 0
animals O 0
, O 0
this O 0
finding O 0
may O 0
help O 0
our O 0
understanding O 0
of O 0
the O 0
coupling O 0
between O 0
cortical O 0
spreading O 0
depression B-Disease 0
and O 0
headache B-Disease 0
in O 0
migraine B-Disease 0
with I-Disease 0
aura I-Disease 0
. O 0

Rapid O 0
reversal O 0
of O 0
life O 0
- O 0
threatening O 0
diltiazem B-Chemical 0
- O 0
induced O 0
tetany B-Disease 0
with O 0
calcium B-Chemical 0
chloride I-Chemical 0
. O 0

We O 0
describe O 0
a O 0
patient O 0
who O 0
developed O 0
tetany B-Disease 0
with O 0
sudden O 0
respiratory B-Disease 0
arrest I-Disease 0
after O 0
the O 0
infusion O 0
of O 0
intravenous O 0
diltiazem B-Chemical 0
. O 0

The O 0
administration O 0
of O 0
calcium B-Chemical 0
chloride I-Chemical 0
rapidly O 0
resolved O 0
the O 0
patient O 0
' O 0
s O 0
tetany B-Disease 0
with O 0
prompt O 0
recovery O 0
of O 0
respiratory O 0
function O 0
, O 0
averting O 0
the O 0
need O 0
for O 0
more O 0
aggressive O 0
airway O 0
management O 0
and O 0
ventilatory O 0
support O 0
. O 0

The O 0
emergency O 0
physician O 0
should O 0
be O 0
aware O 0
that O 0
life O 0
- O 0
threatening O 0
tetany B-Disease 0
may O 0
accompany O 0
the O 0
administration O 0
of O 0
intravenous O 0
diltiazem B-Chemical 0
and O 0
that O 0
calcium B-Chemical 0
chloride I-Chemical 0
may O 0
be O 0
a O 0
rapid O 0
and O 0
effective O 0
remedy O 0
. O 0

Predictors O 0
of O 0
decreased B-Disease 0
renal I-Disease 0
function I-Disease 0
in O 0
patients O 0
with O 0
heart B-Disease 0
failure I-Disease 0
during O 0
angiotensin B-Chemical 0
- O 0
converting O 0
enzyme O 0
inhibitor O 0
therapy O 0
: O 0
results O 0
from O 0
the O 0
studies O 0
of O 0
left B-Disease 0
ventricular I-Disease 0
dysfunction I-Disease 0
( O 0
SOLVD O 0
) O 0

BACKGROUND O 0
: O 0
Although O 0
angiotensin B-Chemical 0
- O 0
converting O 0
enzyme O 0
inhibitor O 0
therapy O 0
reduces O 0
mortality O 0
rates O 0
in O 0
patients O 0
with O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
( O 0
CHF B-Disease 0
) O 0
, O 0
it O 0
may O 0
also O 0
cause O 0
decreased B-Disease 0
renal I-Disease 0
function I-Disease 0
. O 0

Little O 0
information O 0
is O 0
available O 0
to O 0
predict O 0
which O 0
patients O 0
are O 0
at O 0
highest O 0
risk O 0
for O 0
this O 0
complication O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
quantify O 0
specific O 0
clinical O 0
predictors O 0
of O 0
reduction B-Disease 0
in I-Disease 0
renal I-Disease 0
function I-Disease 0
in O 0
patients O 0
with O 0
CHF B-Disease 0
who O 0
are O 0
prescribed O 0
angiotensin B-Chemical 0
- O 0
converting O 0
enzyme O 0
inhibitor O 0
therapy O 0
. O 0

METHOD O 0
: O 0
We O 0
analyzed O 0
data O 0
from O 0
the O 0
Studies O 0
of O 0
Left B-Disease 0
Ventricular I-Disease 0
Dysfunction I-Disease 0
( O 0
SOLVD O 0
) O 0
, O 0
a 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
trial O 0
of O 0
enalapril B-Chemical 0
for O 0
the O 0
treatment O 0
of O 0
CHF B-Disease 0
. O 0

There O 0
were O 0
3379 O 0
patients O 0
randomly O 0
assigned O 0
to O 0
enalapril B-Chemical 0
with O 0
a O 0
median O 0
follow O 0
- O 0
up O 0
of O 0
974 O 0
days O 0
and O 0
3379 O 0
patients O 0
randomly O 0
assigned O 0
to O 0
placebo O 0
with O 0
a O 0
mean O 0
follow O 0
- O 0
up O 0
of O 0
967 O 0
days O 0
. O 0

Decreased B-Disease 0
renal I-Disease 0
function I-Disease 0
was O 0
defined O 0
as O 0
a O 0
rise O 0
in O 0
serum O 0
creatinine B-Chemical 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
44 O 0
micromol O 0
/ O 0
L O 0
) O 0
from O 0
baseline O 0
. O 0

We O 0
used O 0
time O 0
- O 0
to O 0
- O 0
event O 0
analysis O 0
to O 0
identify O 0
potential O 0
predictors O 0
of O 0
decrease O 0
in O 0
renal O 0
function O 0
including O 0
age O 0
, O 0
baseline O 0
ejection O 0
fraction O 0
, O 0
baseline O 0
creatinine B-Chemical 0
, O 0
low O 0
systolic O 0
blood O 0
pressure O 0
( O 0
< O 0
100 O 0
mm O 0
Hg O 0
) O 0
, O 0
history O 0
of O 0
hypertension B-Disease 0
, O 0
diabetes B-Disease 0
, O 0
and O 0
use O 0
of O 0
antiplatelet O 0
, O 0
diuretic B-Chemical 0
, O 0
and O 0
beta O 0
- O 0
blocker O 0
therapy O 0
. O 0

RESULTS O 0
: O 0
Patients O 0
randomly O 0
assigned O 0
to O 0
enalapril B-Chemical 0
had O 0
a O 0
33 O 0
% O 0
greater O 0
likelihood O 0
of O 0
decreased B-Disease 0
renal I-Disease 0
function I-Disease 0
than O 0
controls O 0
( O 0
P O 0
= O 0
. O 0
003 O 0
) O 0
. O 0

By O 0
multivariate O 0
analysis O 0
, O 0
in O 0
both O 0
the O 0
placebo O 0
and O 0
enalapril B-Chemical 0
groups O 0
older O 0
age O 0
, O 0
diuretic B-Chemical 0
therapy O 0
, O 0
and O 0
diabetes B-Disease 0
were O 0
associated O 0
with O 0
decreased B-Disease 0
renal I-Disease 0
function I-Disease 0
, O 0
whereas O 0
beta O 0
- O 0
blocker O 0
therapy O 0
and O 0
higher O 0
ejection O 0
fraction O 0
were O 0
renoprotective O 0
. O 0

Older O 0
age O 0
was O 0
associated O 0
with O 0
a O 0
greater O 0
risk O 0
of O 0
developing O 0
decreased B-Disease 0
renal I-Disease 0
function I-Disease 0
in O 0
both O 0
groups O 0
, O 0
but O 0
significantly O 0
more O 0
so O 0
in O 0
the O 0
enalapril B-Chemical 0
group O 0
( O 0
enalapril B-Chemical 0
: O 0
risk O 0
ratio O 0
[ O 0
RR O 0
] O 0
1 O 0
. O 0
42 O 0
per O 0
10 O 0
years O 0
, O 0
95 O 0
% O 0
confidence O 0
interval O 0
[ O 0
CI O 0
] O 0
1 O 0
. O 0
32 O 0
- O 0
1 O 0
. O 0
52 O 0
with O 0
enalapril B-Chemical 0
; O 0
placebo O 0
: O 0
RR O 0
1 O 0
. O 0
18 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
12 O 0
- O 0
1 O 0
. O 0
25 O 0
) O 0
. O 0

Diuretic B-Chemical 0
therapy O 0
was O 0
likewise O 0
associated O 0
with O 0
a O 0
greater O 0
risk O 0
of O 0
decreased B-Disease 0
renal I-Disease 0
function I-Disease 0
in O 0
the O 0
enalapril B-Chemical 0
group O 0
( O 0
RR O 0
1 O 0
. O 0
89 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
70 O 0
- O 0
2 O 0
. O 0
08 O 0
) O 0
than O 0
in O 0
the O 0
placebo O 0
group O 0
( O 0
RR O 0
1 O 0
. O 0
35 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
09 O 0
- O 0
1 O 0
. O 0
66 O 0
) O 0
. O 0

Conversely O 0
, O 0
enalapril B-Chemical 0
had O 0
a O 0
relative O 0
renoprotective O 0
effect O 0
( O 0
RR O 0
1 O 0
. O 0
33 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
13 O 0
- O 0
1 O 0
. O 0
53 O 0
) O 0
compared O 0
with O 0
placebo O 0
( O 0
RR O 0
1 O 0
. O 0
96 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
57 O 0
- O 0
2 O 0
. O 0
44 O 0
) O 0
in O 0
patients O 0
with O 0
diabetes B-Disease 0
. O 0

A O 0
lower O 0
risk O 0
of O 0
renal B-Disease 0
impairment I-Disease 0
was O 0
seen O 0
in O 0
both O 0
groups O 0
with O 0
beta O 0
- O 0
blocker O 0
therapy O 0
( O 0
RR O 0
0 O 0
. O 0
70 O 0
, O 0
95 O 0
% O 0
CI O 0
0 O 0
. O 0
57 O 0
- O 0
0 O 0
. O 0
85 O 0
) O 0
and O 0
higher O 0
baseline O 0
ejection O 0
fraction O 0
( O 0
RR O 0
0 O 0
. O 0
93 O 0
per O 0
5 O 0
% O 0
increment O 0
, O 0
95 O 0
% O 0
CI O 0
0 O 0
. O 0
91 O 0
- O 0
0 O 0
. O 0
96 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Enalapril B-Chemical 0
use O 0
caused O 0
a O 0
33 O 0
% O 0
increase O 0
in O 0
the O 0
risk O 0
of O 0
decreased B-Disease 0
renal I-Disease 0
function I-Disease 0
in O 0
patients O 0
with O 0
CHF B-Disease 0
. O 0

Diuretic B-Chemical 0
use O 0
and O 0
advanced O 0
age O 0
increased O 0
this O 0
risk O 0
. O 0

Diabetes B-Disease 0
was O 0
associated O 0
with O 0
an O 0
increased O 0
risk O 0
of O 0
renal B-Disease 0
impairment I-Disease 0
in O 0
all O 0
patients O 0
with O 0
CHF B-Disease 0
, O 0
but O 0
this O 0
risk O 0
was O 0
reduced O 0
in O 0
the O 0
enalapril B-Chemical 0
group O 0
compared O 0
with O 0
the O 0
placebo O 0
group O 0
. O 0

beta O 0
- O 0
Blocker O 0
therapy O 0
and O 0
higher O 0
ejection O 0
fraction O 0
were O 0
renoprotective O 0
in O 0
all O 0
patients O 0
regardless O 0
of O 0
therapy O 0
. O 0

Hypomania B-Disease 0
- O 0
like O 0
syndrome O 0
induced O 0
by O 0
olanzapine B-Chemical 0
. O 0

We O 0
report O 0
a O 0
female O 0
patient O 0
with O 0
a O 0
diagnosis O 0
of O 0
a O 0
not O 0
otherwise O 0
specified O 0
psychotic B-Disease 0
disorder I-Disease 0
( O 0
DSM O 0
- O 0
IV O 0
) O 0
who O 0
developed O 0
hypomania B-Disease 0
shortly O 0
after O 0
the O 0
introduction O 0
of O 0
olanzapine B-Chemical 0
treatment O 0
. O 0

Acetazolamide B-Chemical 0
- O 0
induced O 0
Gerstmann B-Disease 0
syndrome I-Disease 0
. O 0

Acute O 0
confusion B-Disease 0
induced O 0
by O 0
acetazolamide B-Chemical 0
is O 0
a O 0
well O 0
known O 0
adverse O 0
drug O 0
reaction O 0
in O 0
patients O 0
with O 0
renal B-Disease 0
impairment I-Disease 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
acetazolamide B-Chemical 0
- O 0
induced O 0
Gerstmann B-Disease 0
syndrome I-Disease 0
in O 0
a O 0
patient O 0
with O 0
normal O 0
renal O 0
function O 0
, O 0
to O 0
highlight O 0
predisposing O 0
factors O 0
that O 0
are O 0
frequently O 0
overlooked O 0
. O 0

Vasopressin B-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
milrinone B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
in O 0
severe O 0
heart B-Disease 0
failure I-Disease 0
. O 0

The O 0
use O 0
of O 0
phosphodiesterase O 0
inhibitors O 0
such O 0
as O 0
milrinone B-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
severe O 0
heart B-Disease 0
failure I-Disease 0
is O 0
frequently O 0
restricted O 0
because O 0
they O 0
cause O 0
vasodilation O 0
and O 0
hypotension B-Disease 0
. O 0

In O 0
patients O 0
with O 0
decompensated O 0
heart B-Disease 0
failure I-Disease 0
with O 0
hypotension B-Disease 0
after O 0
treatment O 0
with O 0
milrinone B-Chemical 0
, O 0
low O 0
doses O 0
of O 0
vasopressin B-Chemical 0
restored O 0
blood O 0
pressure O 0
without O 0
inhibiting O 0
the O 0
inotropic O 0
effect O 0
of O 0
milrinone B-Chemical 0
. O 0

Treatment O 0
of O 0
tacrolimus B-Chemical 0
- O 0
related O 0
adverse O 0
effects O 0
by O 0
conversion O 0
to O 0
cyclosporine B-Chemical 0
in O 0
liver O 0
transplant O 0
recipients O 0
. O 0

When O 0
tacrolimus B-Chemical 0
side O 0
effects O 0
persist O 0
despite O 0
dose O 0
reduction O 0
, O 0
conversion O 0
to O 0
cyclosporine B-Chemical 0
- O 0
based O 0
immunosuppression O 0
( O 0
CyA O 0
) O 0
is O 0
necessary O 0
. O 0

We O 0
characterized O 0
tacrolimus B-Chemical 0
side O 0
effects O 0
that O 0
warranted O 0
discontinuation O 0
of O 0
the O 0
drug O 0
, O 0
and O 0
outcomes O 0
after O 0
conversion O 0
. O 0

Of O 0
388 O 0
liver O 0
recipients O 0
who O 0
received O 0
tacrolimus B-Chemical 0
as O 0
primary O 0
immunosuppression O 0
, O 0
70 O 0
required O 0
conversion O 0
to O 0
CyA O 0
. O 0

We O 0
recorded O 0
indication O 0
for O 0
conversion O 0
, O 0
whether O 0
conversion O 0
was O 0
early O 0
or O 0
late O 0
after O 0
transplantation O 0
, O 0
tacrolimus B-Chemical 0
dose O 0
and O 0
trough O 0
blood O 0
level O 0
at O 0
conversion O 0
, O 0
and O 0
incidence O 0
of O 0
rejection O 0
after O 0
conversion O 0
. O 0

Conversion O 0
was O 0
early O 0
in O 0
29 O 0
patients O 0
( O 0
41 O 0
. O 0
4 O 0
% O 0
) O 0
and O 0
late O 0
in O 0
41 O 0
( O 0
58 O 0
. O 0
6 O 0
% O 0
) O 0
. O 0

Indications O 0
for O 0
early O 0
conversion O 0
were O 0
neurotoxicity B-Disease 0
( O 0
20 O 0
) O 0
, O 0
( B-Disease 0
insulin I-Disease 0
- I-Disease 0
dependent I-Disease 0
) I-Disease 0
diabetes I-Disease 0
mellitus I-Disease 0
( O 0
IDDM B-Disease 0
) O 0
( O 0
5 O 0
) O 0
, O 0
nephrotoxicity B-Disease 0
( O 0
3 O 0
) O 0
, O 0
gastrointestinal B-Disease 0
( I-Disease 0
GI I-Disease 0
) I-Disease 0
toxicity I-Disease 0
( O 0
6 O 0
) O 0
, O 0
and O 0
cardiomyopathy B-Disease 0
( O 0
1 O 0
) O 0
, O 0
and O 0
for O 0
late O 0
conversion O 0
were O 0
neurotoxicity B-Disease 0
( O 0
15 O 0
) O 0
, O 0
IDDM B-Disease 0
( O 0
12 O 0
) O 0
, O 0
nephrotoxicity B-Disease 0
( O 0
3 O 0
) O 0
, O 0
GI B-Disease 0
toxicity I-Disease 0
( O 0
5 O 0
) O 0
, O 0
hepatotoxicity B-Disease 0
( O 0
6 O 0
) O 0
, O 0
post B-Disease 0
- I-Disease 0
transplant I-Disease 0
lmphoproliferate I-Disease 0
disease I-Disease 0
( O 0
PTLD B-Disease 0
) O 0
( O 0
2 O 0
) O 0
, O 0
cardiomyopathy B-Disease 0
( O 0
1 O 0
) O 0
, O 0
hemolytic B-Disease 0
anemia I-Disease 0
( O 0
1 O 0
) O 0
, O 0
and O 0
pruritus B-Disease 0
( O 0
1 O 0
) O 0
. O 0

All O 0
early O 0
- O 0
conversion O 0
patients O 0
showed O 0
improvement O 0
/ O 0
resolution O 0
of O 0
symptoms O 0
. O 0

Among O 0
late O 0
- O 0
conversion O 0
patients O 0
, O 0
37 O 0
( O 0
90 O 0
. O 0
2 O 0
% O 0
) O 0
had O 0
improvement O 0
/ O 0
resolution O 0
; O 0
in O 0
4 O 0
( O 0
9 O 0
. O 0
8 O 0
% O 0
) O 0
, O 0
adverse O 0
effects O 0
persisted O 0
. O 0

The O 0
overall O 0
rejection O 0
rate O 0
was O 0
30 O 0
% O 0
. O 0

Sixty O 0
- O 0
two O 0
patients O 0
( O 0
88 O 0
. O 0
6 O 0
% O 0
) O 0
are O 0
alive O 0
with O 0
functioning O 0
grafts O 0
686 O 0
+ O 0
/ O 0
- O 0
362 O 0
days O 0
( O 0
range O 0
, O 0
154 O 0
- O 0
1433 O 0
days O 0
) O 0
after O 0
conversion O 0
. O 0

When O 0
tacrolimus B-Chemical 0
side O 0
effects O 0
are O 0
unresponsive O 0
to O 0
dose O 0
reduction O 0
, O 0
conversion O 0
to O 0
CyA O 0
can O 0
be O 0
accomplished O 0
safely O 0
, O 0
with O 0
no O 0
increased O 0
risk O 0
of O 0
rejection O 0
and O 0
excellent O 0
long O 0
- O 0
term O 0
outcome O 0
. O 0

Ocular O 0
manifestations O 0
of O 0
juvenile B-Disease 0
rheumatoid I-Disease 0
arthritis I-Disease 0
. O 0

We O 0
followed O 0
210 O 0
cases O 0
of O 0
juvenile B-Disease 0
rheumatoid I-Disease 0
arthritis I-Disease 0
closely O 0
for O 0
eleven O 0
years O 0
. O 0

Thirty O 0
- O 0
six O 0
of O 0
the O 0
210 O 0
patients O 0
( O 0
17 O 0
. O 0
2 O 0
% O 0
) O 0
developed O 0
iridocyclitis B-Disease 0
. O 0

Iridocyclitis B-Disease 0
was O 0
seen O 0
most O 0
frequently O 0
in O 0
young O 0
female O 0
patients O 0
( O 0
0 O 0
to O 0
4 O 0
years O 0
) O 0
with O 0
the O 0
monoarticular O 0
or O 0
pauciatricular O 0
form O 0
of O 0
the O 0
arthritis B-Disease 0
. O 0

However O 0
, O 0
30 O 0
% O 0
of O 0
the O 0
patients O 0
developed O 0
uveitis B-Disease 0
after O 0
16 O 0
years O 0
of O 0
age O 0
. O 0

Although O 0
61 O 0
% O 0
of O 0
patients O 0
had O 0
a O 0
noncontributory O 0
ocular O 0
history O 0
on O 0
entry O 0
, O 0
42 O 0
% O 0
had O 0
active O 0
uveitis B-Disease 0
on O 0
entry O 0
. O 0

Our O 0
approach O 0
was O 0
effective O 0
in O 0
detecting O 0
uveitis B-Disease 0
in O 0
new O 0
cases O 0
and O 0
exacerbations O 0
of O 0
uveitis B-Disease 0
in O 0
established O 0
cases O 0
. O 0

Forty O 0
- O 0
four O 0
percent O 0
of O 0
patients O 0
with O 0
uveitis B-Disease 0
had O 0
one O 0
or O 0
more O 0
identifiable O 0
signs O 0
or O 0
symptoms O 0
, O 0
such O 0
as O 0
red O 0
eye O 0
, O 0
ocular B-Disease 0
pain I-Disease 0
, O 0
decreased B-Disease 0
visual I-Disease 0
acuity I-Disease 0
, O 0
or O 0
photophobia B-Disease 0
, O 0
in O 0
order O 0
of O 0
decreasing O 0
frequency O 0
. O 0

Even O 0
after O 0
early O 0
detection O 0
and O 0
prompt O 0
treatment O 0
, O 0
41 O 0
% O 0
of O 0
cases O 0
of O 0
uveitis B-Disease 0
did O 0
not O 0
respond O 0
to O 0
more O 0
than O 0
six O 0
months O 0
of O 0
intensive O 0
topical O 0
treatment O 0
with O 0
corticosteroids B-Chemical 0
and O 0
mydriatics O 0
. O 0

Despite O 0
this O 0
, O 0
there O 0
was O 0
a O 0
dramatic O 0
decrease O 0
in O 0
the O 0
50 O 0
% O 0
incidence O 0
of O 0
blinding O 0
complications O 0
of O 0
uveitis B-Disease 0
cited O 0
in O 0
earlier O 0
studies O 0
. O 0

Cataract B-Disease 0
and O 0
band B-Disease 0
keratopathy I-Disease 0
occurred O 0
in O 0
only O 0
22 O 0
and O 0
13 O 0
% O 0
of O 0
our O 0
group O 0
, O 0
respectively O 0
. O 0

We O 0
used O 0
chloroquine B-Chemical 0
or O 0
hydroxychloroquine B-Chemical 0
in O 0
173 O 0
of O 0
210 O 0
cases O 0
and O 0
found O 0
only O 0
one O 0
case O 0
of O 0
chorioretinopathy B-Disease 0
attributable O 0
to O 0
these O 0
drugs O 0
. O 0

Systemically O 0
administered O 0
corticosteroids B-Chemical 0
were O 0
used O 0
in O 0
75 O 0
of O 0
210 O 0
cases O 0
; O 0
a O 0
significant O 0
number O 0
of O 0
posterior O 0
subcapsular O 0
cataracts B-Disease 0
was O 0
found O 0
. O 0

Typical O 0
keratoconjunctivitis B-Disease 0
sicca O 0
developed O 0
in O 0
three O 0
of O 0
the O 0
uveitis B-Disease 0
cases O 0
. O 0

This O 0
association O 0
with O 0
uveitis B-Disease 0
and O 0
JRA O 0
was O 0
not O 0
noted O 0
previously O 0
. O 0

Surgical O 0
treatment O 0
of O 0
cataracts B-Disease 0
, O 0
band B-Disease 0
keratopathy I-Disease 0
, O 0
and O 0
glaucoma B-Disease 0
achieved O 0
uniformly O 0
discouraging O 0
results O 0
. O 0

Cyclophosphamide B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
in O 0
freely O 0
- O 0
moving O 0
conscious O 0
rats O 0
: O 0
behavioral O 0
approach O 0
to O 0
a O 0
new O 0
model O 0
of O 0
visceral B-Disease 0
pain I-Disease 0
. O 0

PURPOSE O 0
: O 0
To O 0
develop O 0
a O 0
model O 0
of O 0
visceral B-Disease 0
pain I-Disease 0
in O 0
rats O 0
using O 0
a O 0
behavioral O 0
approach O 0
. O 0

Cyclophosphamide B-Chemical 0
( O 0
CP B-Chemical 0
) O 0
, O 0
an O 0
antitumoral O 0
agent O 0
known O 0
to O 0
produce O 0
toxic O 0
effects O 0
on O 0
the O 0
bladder O 0
wall O 0
through O 0
its O 0
main O 0
toxic O 0
metabolite O 0
acrolein B-Chemical 0
, O 0
was O 0
used O 0
to O 0
induce O 0
cystitis B-Disease 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
CP B-Chemical 0
was O 0
administered O 0
at O 0
doses O 0
of O 0
50 O 0
, O 0
100 O 0
and O 0
200 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0

i O 0
. O 0
p O 0
. O 0
to O 0
male O 0
rats O 0
, O 0
and O 0
their O 0
behavior O 0
observed O 0
and O 0
scored O 0
. O 0

The O 0
effects O 0
of O 0
morphine B-Chemical 0
( O 0
0 O 0
. O 0
5 O 0
to O 0
4 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0
i O 0
. O 0
v O 0
. O 0
) O 0
on O 0
CP B-Chemical 0
- O 0
induced O 0
behavioral O 0
modifications O 0
were O 0
tested O 0
administered O 0
alone O 0
and O 0
after O 0
naloxone B-Chemical 0
( O 0
1 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0
s O 0
. O 0
c O 0
. O 0
) O 0
. O 0

In O 0
addition O 0
, O 0
90 O 0
minutes O 0
after O 0
CP B-Chemical 0
injection O 0
, O 0
that O 0
is O 0
, O 0
at O 0
the O 0
time O 0
of O 0
administration O 0
of O 0
morphine B-Chemical 0
, O 0
the O 0
bladder O 0
was O 0
removed O 0
in O 0
some O 0
rats O 0
for O 0
histological O 0
examination O 0
. O 0

Finally O 0
, O 0
to O 0
show O 0
that O 0
the O 0
bladder O 0
is O 0
essential O 0
for O 0
the O 0
CP B-Chemical 0
- O 0
induced O 0
behavioral O 0
modifications O 0
, O 0
female O 0
rats O 0
also O 0
received O 0
CP B-Chemical 0
at O 0
doses O 0
of O 0
200 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0

i O 0
. O 0
p O 0
. O 0
and O 0
of O 0
20 O 0
mg O 0
. O 0
by O 0
the O 0
intravesical O 0
route O 0
, O 0
and O 0
acrolein B-Chemical 0
at O 0
doses O 0
of O 0
0 O 0
. O 0
5 O 0
mg O 0
. O 0
by O 0
the O 0
intravesical O 0
route O 0
and O 0
of O 0
5 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0

i O 0
. O 0
v O 0
. O 0
RESULTS O 0
: O 0
CP B-Chemical 0
dose O 0
- O 0
relatedly O 0
induced O 0
marked O 0
behavioral O 0
modifications O 0
in O 0
male O 0
rats O 0
: O 0
breathing O 0
rate O 0
decrease O 0
, O 0
closing O 0
of O 0
the O 0
eyes O 0
and O 0
occurrence O 0
of O 0
specific O 0
postures O 0
. O 0

Morphine B-Chemical 0
dose O 0
- O 0
dependently O 0
reversed O 0
these O 0
behavioral B-Disease 0
disorders I-Disease 0
. O 0

A O 0
dose O 0
of O 0
0 O 0
. O 0
5 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0
produced O 0
a O 0
reduction O 0
of O 0
almost O 0
50 O 0
% O 0
of O 0
the O 0
behavioral O 0
score O 0
induced O 0
by O 0
CP B-Chemical 0
200 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0

This O 0
effect O 0
was O 0
completely O 0
prevented O 0
by O 0
pretreatment O 0
with O 0
naloxone B-Chemical 0
. O 0

At O 0
the O 0
time O 0
of O 0
administration O 0
of O 0
morphine B-Chemical 0
, O 0
histological O 0
modifications O 0
of O 0
the O 0
bladder O 0
wall O 0
, O 0
such O 0
as O 0
chorionic O 0
and O 0
muscle O 0
layer O 0
edema B-Disease 0
, O 0
were O 0
observed O 0
. O 0

In O 0
female O 0
rats O 0
, O 0
CP B-Chemical 0
200 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0

i O 0
. O 0
p O 0
. O 0
produced O 0
the O 0
same O 0
marked O 0
behavioral O 0
modifications O 0
as O 0
those O 0
observed O 0
in O 0
male O 0
rats O 0
. O 0

Administered O 0
at O 0
the O 0
dose O 0
of O 0
20 O 0
mg O 0
. O 0
intravesically O 0
, O 0
CP B-Chemical 0
did O 0
not O 0
produce O 0
any O 0
behavioral O 0
effects O 0
, O 0
whereas O 0
acrolein B-Chemical 0
at O 0
0 O 0
. O 0
5 O 0
mg O 0
. O 0
intravesically O 0
induced O 0
behavioral O 0
modifications O 0
identical O 0
to O 0
those O 0
under O 0
CP B-Chemical 0
200 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0

i O 0
. O 0
p O 0
. O 0
, O 0
with O 0
the O 0
same O 0
maximal O 0
levels O 0
. O 0

Conversely O 0
, O 0
acrolein B-Chemical 0
5 O 0
mg O 0
. O 0
/ O 0
kg O 0
. O 0

i O 0
. O 0
v O 0
. O 0
did O 0
not O 0
produce O 0
any O 0
behavioral O 0
effects O 0
at O 0
all O 0
. O 0

CONCLUSIONS O 0
: O 0
Overall O 0
, O 0
these O 0
results O 0
indicate O 0
that O 0
this O 0
experimental O 0
model O 0
of O 0
CP B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
may O 0
be O 0
an O 0
interesting O 0
new O 0
behavioral O 0
model O 0
of O 0
inflammatory O 0
visceral B-Disease 0
pain I-Disease 0
, O 0
allowing O 0
a O 0
better O 0
understanding O 0
of O 0
these O 0
painful B-Disease 0
syndromes I-Disease 0
and O 0
thus O 0
a O 0
better O 0
therapeutic O 0
approach O 0
to O 0
them O 0
. O 0

Prednisolone B-Chemical 0
- O 0
induced O 0
muscle B-Disease 0
dysfunction I-Disease 0
is O 0
caused O 0
more O 0
by O 0
atrophy B-Disease 0
than O 0
by O 0
altered O 0
acetylcholine B-Chemical 0
receptor O 0
expression O 0
. O 0

Large O 0
doses O 0
of O 0
glucocorticoids O 0
can O 0
alter O 0
muscle O 0
physiology O 0
and O 0
susceptibility O 0
to O 0
neuromuscular O 0
blocking O 0
drugs O 0
by O 0
mechanisms O 0
not O 0
clearly O 0
understood O 0
. O 0

We O 0
investigated O 0
the O 0
effects O 0
of O 0
moderate O 0
and O 0
large O 0
doses O 0
of O 0
prednisolone B-Chemical 0
on O 0
muscle O 0
function O 0
and O 0
pharmacology O 0
, O 0
and O 0
their O 0
relationship O 0
to O 0
changes O 0
in O 0
muscle O 0
size O 0
and O 0
acetylcholine B-Chemical 0
receptor O 0
( O 0
AChR O 0
) O 0
expression O 0
. O 0

With O 0
institutional O 0
approval O 0
, O 0
35 O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
were O 0
randomly O 0
allocated O 0
to O 0
receive O 0
daily O 0
subcutaneous O 0
doses O 0
of O 0
10 O 0
mg O 0
/ O 0
kg O 0
prednisolone B-Chemical 0
( O 0
P10 O 0
group O 0
) O 0
, O 0
100 O 0
mg O 0
/ O 0
kg O 0
prednisolone B-Chemical 0
( O 0
P100 O 0
group O 0
) O 0
, O 0
or O 0
an O 0
equal O 0
volume O 0
of O 0
saline O 0
( O 0
S O 0
group O 0
) O 0
for O 0
7 O 0
days O 0
. O 0

A O 0
fourth O 0
group O 0
of O 0
rats O 0
was O 0
pair O 0
fed O 0
( O 0
food O 0
restricted O 0
) O 0
with O 0
the O 0
P100 O 0
rats O 0
for O 0
7 O 0
days O 0
( O 0
FR O 0
group O 0
) O 0
. O 0

On O 0
Day O 0
8 O 0
, O 0
the O 0
nerve O 0
- O 0
evoked O 0
peak O 0
twitch O 0
tensions O 0
, O 0
tetanic B-Disease 0
tensions O 0
, O 0
and O 0
fatigability O 0
, O 0
and O 0
the O 0
dose O 0
- O 0
response O 0
curves O 0
of O 0
d B-Chemical 0
- I-Chemical 0
tubocurarine I-Chemical 0
in O 0
the O 0
tibialis O 0
cranialis O 0
muscle O 0
were O 0
measured O 0
in O 0
vivo O 0
and O 0
related O 0
to O 0
muscle O 0
mass O 0
or O 0
expression O 0
of O 0
AChRs O 0
. O 0

Rate O 0
of O 0
body O 0
weight O 0
gain O 0
was O 0
depressed O 0
in O 0
the O 0
P100 O 0
, O 0
FR O 0
, O 0
and O 0
P10 O 0
groups O 0
compared O 0
with O 0
the O 0
S O 0
group O 0
. O 0

Tibialis O 0
muscle O 0
mass O 0
was O 0
smaller O 0
in O 0
the O 0
P100 O 0
group O 0
than O 0
in O 0
the O 0
P10 O 0
or O 0
S O 0
groups O 0
. O 0

The O 0
evoked O 0
peak O 0
twitch O 0
and O 0
tetanic B-Disease 0
tensions O 0
were O 0
less O 0
in O 0
the O 0
P100 O 0
group O 0
than O 0
in O 0
the O 0
P10 O 0
or O 0
S O 0
groups O 0
, O 0
however O 0
, O 0
tension O 0
per O 0
milligram O 0
of O 0
muscle O 0
mass O 0
was O 0
greater O 0
in O 0
the O 0
P100 O 0
group O 0
than O 0
in O 0
the O 0
S O 0
group O 0
. O 0

The O 0
50 O 0
% O 0
effective O 0
dose O 0
of O 0
d B-Chemical 0
- I-Chemical 0
tubocurarine I-Chemical 0
( O 0
microg O 0
/ O 0
kg O 0
) O 0
in O 0
the O 0
tibialis O 0
muscle O 0
was O 0
smaller O 0
in O 0
the O 0
P10 O 0
( O 0
33 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
5 O 0
. O 0
4 O 0
) O 0
than O 0
in O 0
the O 0
S O 0
( O 0
61 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
5 O 0
. O 0
0 O 0
) O 0
or O 0
the O 0
P100 O 0
( O 0
71 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
9 O 0
. O 0
6 O 0
) O 0
groups O 0
. O 0

AChR O 0
expression O 0
was O 0
less O 0
in O 0
the O 0
P10 O 0
group O 0
than O 0
in O 0
the O 0
S O 0
group O 0
. O 0

The O 0
evoked O 0
tensions O 0
correlated O 0
with O 0
muscle O 0
mass O 0
( O 0
r O 0
( O 0
2 O 0
) O 0
= O 0
0 O 0
. O 0
32 O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
, O 0
however O 0
, O 0
not O 0
with O 0
expression O 0
of O 0
AChR O 0
. O 0

The O 0
50 O 0
% O 0
effective O 0
dose O 0
of O 0
d B-Chemical 0
- I-Chemical 0
tubocurarine I-Chemical 0
did O 0
not O 0
correlate O 0
with O 0
muscle O 0
mass O 0
or O 0
AChR O 0
expression O 0
. O 0

Our O 0
results O 0
suggest O 0
that O 0
the O 0
neuromuscular B-Disease 0
dysfunction I-Disease 0
after O 0
prednisolone B-Chemical 0
is O 0
dose O 0
- O 0
dependent O 0
, O 0
and O 0
derives O 0
primarily O 0
from O 0
muscle B-Disease 0
atrophy I-Disease 0
and O 0
derives O 0
less O 0
so O 0
from O 0
changes O 0
in O 0
AChR O 0
expression O 0
. O 0

IMPLICATIONS O 0
: O 0
The O 0
mechanisms O 0
by O 0
which O 0
chronic O 0
glucocorticoid O 0
therapy O 0
alters O 0
neuromuscular O 0
physiology O 0
and O 0
pharmacology O 0
are O 0
unclear O 0
. O 0

We O 0
suggest O 0
that O 0
the O 0
observed O 0
effects O 0
are O 0
dose O 0
- O 0
dependent O 0
and O 0
derive O 0
primarily O 0
from O 0
muscle B-Disease 0
atrophy I-Disease 0
and O 0
derive O 0
less O 0
from O 0
changes O 0
in O 0
acetylcholine B-Chemical 0
receptor O 0
expression O 0
. O 0

Apomorphine B-Chemical 0
: O 0
an O 0
underutilized 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

Apomorphine B-Chemical 0
was O 0
the O 0
first O 0
dopaminergic O 0
drug O 0
ever O 0
used O 0
to O 0
treat 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

While O 0
powerful O 0
antiparkinsonian O 0
effects O 0
had O 0
been O 0
observed O 0
as O 0
early O 0
as O 0
1951 O 0
, O 0
the O 0
potential O 0
of O 0
treating O 0
fluctuating O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
by O 0
subcutaneous O 0
administration O 0
of O 0
apomorphine B-Chemical 0
has O 0
only O 0
recently O 0
become O 0
the O 0
subject O 0
of O 0
systematic O 0
study O 0
. O 0

A O 0
number O 0
of O 0
small O 0
scale O 0
clinical O 0
trials O 0
have O 0
unequivocally O 0
shown O 0
that O 0
intermittent O 0
subcutaneous O 0
apomorphine B-Chemical 0
injections O 0
produce O 0
antiparkinsonian O 0
benefit O 0
close O 0
if O 0
not O 0
identical O 0
to O 0
that O 0
seen O 0
with O 0
levodopa B-Chemical 0
and O 0
that O 0
apomorphine B-Chemical 0
rescue O 0
injections O 0
can O 0
reliably O 0
revert O 0
off O 0
- O 0
periods O 0
even O 0
in O 0
patients O 0
with O 0
complex O 0
on O 0
- O 0
off O 0
motor O 0
swings O 0
. O 0

Continuous O 0
subcutaneous O 0
apomorphine B-Chemical 0
infusions O 0
can O 0
reduce O 0
daily O 0
off O 0
- O 0
time O 0
by O 0
more O 0
than O 0
50 O 0
% O 0
in O 0
this O 0
group O 0
of O 0
patients O 0
, O 0
which O 0
appears O 0
to O 0
be O 0
a O 0
stronger O 0
effect O 0
than O 0
that O 0
generally O 0
seen O 0
with O 0
add O 0
- O 0
on O 0
therapy O 0
with O 0
oral O 0
dopamine B-Chemical 0
agonists O 0
or O 0
COMT O 0
inhibitors O 0
. O 0

Extended O 0
follow O 0
- O 0
up O 0
studies O 0
of O 0
up O 0
to O 0
8 O 0
years O 0
have O 0
demonstrated O 0
long O 0
- O 0
term O 0
persistence O 0
of O 0
apomorphine B-Chemical 0
efficacy O 0
. O 0

In O 0
addition O 0
, O 0
there O 0
is O 0
convincing O 0
clinical O 0
evidence O 0
that O 0
monotherapy O 0
with O 0
continuous O 0
subcutaneous O 0
apomorphine B-Chemical 0
infusions O 0
is O 0
associated O 0
with O 0
marked O 0
reductions O 0
of O 0
preexisting O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
. O 0

The O 0
main O 0
side O 0
effects O 0
of O 0
subcutaneous O 0
apomorphine B-Chemical 0
treatment O 0
are O 0
related O 0
to O 0
cutaneous O 0
tolerability O 0
problems O 0
, O 0
whereas O 0
sedation O 0
and O 0
psychiatric B-Disease 0
complications O 0
play O 0
a O 0
lesser O 0
role O 0
. O 0

Given O 0
the O 0
marked O 0
degree O 0
of O 0
efficacy O 0
of O 0
subcutaneous O 0
apomorphine B-Chemical 0
treatment O 0
in O 0
fluctuating O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
, O 0
this O 0
approach O 0
seems O 0
to O 0
deserve O 0
more O 0
widespread O 0
clinical O 0
use O 0
. O 0

Probing O 0
peripheral O 0
and O 0
central O 0
cholinergic O 0
system O 0
responses O 0
. O 0

OBJECTIVE O 0
: O 0
The O 0
pharmacological O 0
response O 0
to O 0
drugs O 0
that O 0
act O 0
on O 0
the O 0
cholinergic O 0
system O 0
of O 0
the O 0
iris O 0
has O 0
been O 0
used O 0
to O 0
predict O 0
deficits O 0
in O 0
central O 0
cholinergic O 0
functioning O 0
due O 0
to O 0
diseases O 0
such O 0
as O 0
Alzheimer B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
, O 0
yet O 0
correlations O 0
between O 0
central O 0
and O 0
peripheral O 0
responses O 0
have O 0
not O 0
been O 0
properly O 0
studied O 0
. O 0

This O 0
study O 0
assessed O 0
the O 0
effect O 0
of O 0
normal O 0
aging O 0
on O 0
( O 0
1 O 0
) O 0
the O 0
tropicamide B-Chemical 0
- O 0
induced O 0
increase O 0
in O 0
pupil O 0
diameter O 0
, O 0
and O 0
( O 0
2 O 0
) O 0
the O 0
reversal O 0
of O 0
this O 0
effect O 0
with O 0
pilocarpine B-Chemical 0
. O 0

Scopolamine B-Chemical 0
was O 0
used O 0
as O 0
a O 0
positive O 0
control O 0
to O 0
detect O 0
age O 0
- O 0
dependent O 0
changes O 0
in O 0
central O 0
cholinergic O 0
functioning O 0
in O 0
the O 0
elderly O 0
. O 0

DESIGN O 0
: O 0
Randomized O 0
double O 0
- O 0
blind O 0
controlled O 0
trial O 0
. O 0

PARTICIPANTS O 0
: O 0
Ten O 0
healthy O 0
elderly O 0
( O 0
mean O 0
age O 0
70 O 0
) O 0
and O 0
9 O 0
young O 0
( O 0
mean O 0
age O 0
33 O 0
) O 0
volunteers O 0
. O 0

INTERVENTIONS O 0
: O 0
Pupil O 0
diameter O 0
was O 0
monitored O 0
using O 0
a O 0
computerized O 0
infrared O 0
pupillometer O 0
over O 0
4 O 0
hours O 0
. O 0

The O 0
study O 0
involved O 0
4 O 0
sessions O 0
. O 0

In O 0
1 O 0
session O 0
, O 0
tropicamide B-Chemical 0
( O 0
20 O 0
microL O 0
, O 0
0 O 0
. O 0
01 O 0
% O 0
) O 0
was O 0
administered O 0
to O 0
one O 0
eye O 0
and O 0
placebo O 0
to O 0
the O 0
other O 0
. O 0

In O 0
another O 0
session O 0
, O 0
tropicamide B-Chemical 0
( O 0
20 O 0
microL O 0
, O 0
0 O 0
. O 0
01 O 0
% O 0
) O 0
was O 0
administered O 0
to O 0
both O 0
eyes O 0
, O 0
followed O 0
23 O 0
minutes O 0
later O 0
by O 0
the O 0
application O 0
of O 0
pilocarpine B-Chemical 0
( O 0
20 O 0
microL O 0
, O 0
0 O 0
. O 0
1 O 0
% O 0
) O 0
to O 0
one O 0
eye O 0
and O 0
placebo O 0
to O 0
the O 0
other O 0
. O 0

All O 0
eye O 0
drops O 0
were O 0
given O 0
in O 0
a O 0
randomized O 0
order O 0
. O 0

In O 0
2 O 0
separate O 0
sessions O 0
, O 0
a O 0
single O 0
dose O 0
of O 0
scopolamine B-Chemical 0
( O 0
0 O 0
. O 0
5 O 0
mg O 0
, O 0
intravenously O 0
) O 0
or O 0
placebo O 0
was O 0
administered O 0
, O 0
and O 0
the O 0
effects O 0
on O 0
word O 0
recall O 0
were O 0
measured O 0
using O 0
the O 0
Buschke O 0
Selective O 0
Reminding O 0
Test O 0
over O 0
2 O 0
hours O 0
. O 0

OUTCOME O 0
MEASURES O 0
: O 0
Pupil O 0
size O 0
at O 0
time O 0
points O 0
after O 0
administration O 0
of O 0
tropicamide B-Chemical 0
and O 0
pilocarpine B-Chemical 0
; O 0
scopolamine B-Chemical 0
- O 0
induced O 0
impairment B-Disease 0
in I-Disease 0
word I-Disease 0
recall I-Disease 0
. O 0

RESULTS O 0
: O 0
There O 0
was O 0
no O 0
significant O 0
difference O 0
between O 0
elderly O 0
and O 0
young O 0
volunteers O 0
in O 0
pupillary O 0
response O 0
to O 0
tropicamide B-Chemical 0
at O 0
any O 0
time O 0
point O 0
( O 0
p O 0
> O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

The O 0
elderly O 0
group O 0
had O 0
a O 0
significantly O 0
greater O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
net O 0
decrease O 0
in O 0
pupil O 0
size O 0
85 O 0
, O 0
125 O 0
, O 0
165 O 0
and O 0
215 O 0
minutes O 0
after O 0
administration O 0
, O 0
compared O 0
with O 0
the O 0
young O 0
group O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Compared O 0
with O 0
the O 0
young O 0
group O 0
, O 0
the O 0
elderly O 0
group O 0
had O 0
greater O 0
scopolamine B-Chemical 0
- O 0
induced O 0
impairment B-Disease 0
in I-Disease 0
word I-Disease 0
recall I-Disease 0
60 O 0
, O 0
90 O 0
and O 0
120 O 0
minutes O 0
after O 0
administration 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
is O 0
an O 0
age O 0
- O 0
related O 0
pupillary O 0
response O 0
to O 0
pilocarpine B-Chemical 0
that O 0
is O 0
not O 0
found O 0
with O 0
tropicamide B-Chemical 0
. O 0

Thus O 0
, O 0
pilocarpine B-Chemical 0
may O 0
be O 0
useful O 0
to O 0
assess O 0
variations O 0
in O 0
central O 0
cholinergic O 0
function O 0
in O 0
elderly O 0
patients O 0
. O 0

Pain B-Disease 0
responses O 0
in O 0
methadone B-Chemical 0
- O 0
maintained O 0
opioid O 0
abusers O 0
. O 0

Providing O 0
pain B-Disease 0
management O 0
for O 0
known O 0
opioid O 0
abusers O 0
is O 0
a O 0
challenging O 0
clinical O 0
task O 0
, O 0
in O 0
part O 0
because O 0
little O 0
is O 0
known O 0
about O 0
their O 0
pain B-Disease 0
experience O 0
and O 0
analgesic O 0
requirements O 0
. O 0

This O 0
study O 0
was O 0
designed O 0
to O 0
describe O 0
pain B-Disease 0
tolerance O 0
and O 0
analgesic O 0
response O 0
in O 0
a O 0
sample O 0
of O 0
opioid B-Disease 0
addicts I-Disease 0
stabilized O 0
in O 0
methadone B-Chemical 0
- O 0
maintenance O 0
( O 0
MM O 0
) O 0
treatment O 0
( O 0
n O 0
= O 0
60 O 0
) O 0
in O 0
comparison O 0
to O 0
matched O 0
nondependent O 0
control O 0
subjects O 0
( O 0
n O 0
= O 0
60 O 0
) O 0
. O 0

By O 0
using O 0
a O 0
placebo O 0
- O 0
controlled O 0
, O 0
two O 0
- O 0
way O 0
factorial O 0
design O 0
, O 0
tolerance O 0
to O 0
cold O 0
- O 0
pressor O 0
( O 0
CP O 0
) O 0
pain B-Disease 0
was O 0
examined O 0
, O 0
both O 0
before O 0
and O 0
after O 0
oral O 0
administration O 0
of O 0
therapeutic O 0
doses O 0
of O 0
common O 0
opioid O 0
( O 0
hydromorphone B-Chemical 0
2 O 0
mg O 0
) O 0
and O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
( O 0
ketorolac B-Chemical 0
10 O 0
mg O 0
) O 0
analgesic O 0
agents O 0
. O 0

Results O 0
showed O 0
that O 0
MM O 0
individuals O 0
were O 0
significantly O 0
less O 0
tolerant O 0
of O 0
CP O 0
pain B-Disease 0
than O 0
control O 0
subjects O 0
, O 0
replicating O 0
previous O 0
work O 0
. O 0

Analgesic O 0
effects O 0
were O 0
significant O 0
neither O 0
for O 0
medication O 0
nor O 0
group O 0
. O 0

These O 0
data O 0
indicate O 0
that O 0
MM O 0
opioid O 0
abusers O 0
represent O 0
a O 0
pain B-Disease 0
- I-Disease 0
intolerant I-Disease 0
subset O 0
of O 0
clinical O 0
patients O 0
. O 0

Their O 0
complaints O 0
of O 0
pain B-Disease 0
should O 0
be O 0
evaluated O 0
seriously O 0
and O 0
managed O 0
aggressively O 0
. O 0

High O 0
- O 0
dose O 0
methylprednisolone B-Chemical 0
may O 0
do O 0
more O 0
harm O 0
for O 0
spinal B-Disease 0
cord I-Disease 0
injury I-Disease 0
. O 0

Because O 0
of O 0
the O 0
National O 0
Acute O 0
Spinal B-Disease 0
Cord I-Disease 0
Injury I-Disease 0
Studies O 0
( O 0
NASCIS O 0
) O 0
, O 0
high O 0
- O 0
dose O 0
methylprednisolone B-Chemical 0
became O 0
the O 0
standard O 0
of O 0
care O 0
for O 0
the O 0
acute O 0
spinal B-Disease 0
cord I-Disease 0
injury I-Disease 0
. O 0

In O 0
the O 0
NASCIS O 0
, O 0
there O 0
was O 0
no O 0
mention O 0
regarding O 0
the O 0
possibility O 0
of O 0
acute O 0
corticosteroid B-Chemical 0
myopathy B-Disease 0
that O 0
high O 0
- O 0
dose O 0
methylprednisolone B-Chemical 0
may O 0
cause O 0
. O 0

The O 0
dosage O 0
of O 0
methylprednisolone B-Chemical 0
recommended O 0
by O 0
the O 0
NASCIS O 0
3 O 0
is O 0
the O 0
highest O 0
dose O 0
of O 0
steroids B-Chemical 0
ever O 0
being O 0
used O 0
during O 0
a O 0
2 O 0
- O 0
day O 0
period O 0
for O 0
any O 0
clinical O 0
condition O 0
. O 0

We O 0
hypothesize O 0
that O 0
it O 0
may O 0
cause O 0
some O 0
damage B-Disease 0
to I-Disease 0
the I-Disease 0
muscle I-Disease 0
of O 0
spinal B-Disease 0
cord I-Disease 0
injury I-Disease 0
patients O 0
. O 0

Further O 0
, O 0
steroid B-Chemical 0
myopathy B-Disease 0
recovers O 0
naturally O 0
and O 0
the O 0
neurological O 0
improvement O 0
shown O 0
in O 0
the O 0
NASCIS O 0
may O 0
be O 0
just O 0
a O 0
recording O 0
of O 0
this O 0
natural O 0
motor O 0
recovery O 0
from O 0
the O 0
steroid B-Chemical 0
myopathy B-Disease 0
, O 0
instead O 0
of O 0
any O 0
protection O 0
that O 0
methylprednisolone B-Chemical 0
offers O 0
to O 0
the O 0
spinal B-Disease 0
cord I-Disease 0
injury I-Disease 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
discussion O 0
considering O 0
the O 0
possibility O 0
that O 0
the O 0
methylprednisolone B-Chemical 0
recommended O 0
by O 0
NASCIS O 0
may O 0
cause O 0
acute O 0
corticosteroid B-Chemical 0
myopathy B-Disease 0
. O 0

Conversion O 0
to O 0
rapamycin B-Chemical 0
immunosuppression O 0
in O 0
renal O 0
transplant O 0
recipients O 0
: O 0
report O 0
of O 0
an O 0
initial O 0
experience O 0
. O 0

BACKGROUND 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
evaluate O 0
the O 0
effects O 0
of O 0
RAPA B-Chemical 0
conversion O 0
in O 0
patients O 0
undergoing O 0
cyclosporine B-Chemical 0
( O 0
CsA B-Chemical 0
) O 0
or O 0
tacrolimus B-Chemical 0
( O 0
Tac B-Chemical 0
) O 0
toxicity B-Disease 0
. O 0

METHODS O 0
: O 0
Twenty O 0
renal O 0
transplant O 0
recipients O 0
were O 0
switched O 0
to O 0
fixed O 0
dose O 0
rapamycin B-Chemical 0
( O 0
RAPA B-Chemical 0
) O 0
( O 0
5 O 0
mg O 0
/ O 0
day O 0
) O 0
0 O 0
to O 0
204 O 0
months O 0
posttransplant O 0
. O 0

Drug O 0
monitoring O 0
was O 0
not O 0
initially O 0
used O 0
to O 0
adjust O 0
doses O 0
. O 0

The O 0
indications O 0
for O 0
switch O 0
were O 0
chronic O 0
CsA B-Chemical 0
or O 0
Tac B-Chemical 0
nephrotoxicity B-Disease 0
( O 0
12 O 0
) O 0
, O 0
acute O 0
CsA B-Chemical 0
or O 0
Tac B-Chemical 0
toxicity B-Disease 0
( O 0
3 O 0
) O 0
, O 0
severe O 0
facial B-Disease 0
dysmorphism I-Disease 0
( O 0
2 O 0
) O 0
, O 0
posttransplant B-Disease 0
lymphoproliferative I-Disease 0
disorder I-Disease 0
( O 0
PTLD B-Disease 0
) O 0
in O 0
remission O 0
( O 0
2 O 0
) O 0
, O 0
and O 0
hepatotoxicity B-Disease 0
in O 0
1 O 0
. O 0

Follow O 0
- O 0
up O 0
is O 0
7 O 0
to O 0
24 O 0
months O 0
. O 0

RESULTS O 0
: O 0
In O 0
the O 0
12 O 0
patients O 0
switched O 0
because O 0
of O 0
chronic O 0
nephrotoxicity B-Disease 0
there O 0
was O 0
a O 0
significant O 0
decrease O 0
in O 0
serum O 0
creatinine B-Chemical 0
[ O 0
233 O 0
+ O 0
/ O 0
- O 0
34 O 0
to O 0
210 O 0
+ O 0
/ O 0
- O 0
56 O 0
micromol O 0
/ O 0
liter O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
at O 0
6 O 0
months O 0
] O 0
. O 0

Facial B-Disease 0
dysmorphism I-Disease 0
improved O 0
in O 0
two O 0
patients O 0
. O 0

No O 0
relapse O 0
of O 0
PTLD B-Disease 0
was O 0
observed O 0
. O 0

Five O 0
patients O 0
developed O 0
pneumonia B-Disease 0
( O 0
two O 0
Pneumocystis B-Disease 0
carinii I-Disease 0
pneumonia I-Disease 0
, O 0
one O 0
infectious B-Disease 0
mononucleosis I-Disease 0
with O 0
polyclonal O 0
PTLD B-Disease 0
lung O 0
infiltrate O 0
) O 0
and O 0
two O 0
had O 0
bronchiolitis B-Disease 0
obliterans I-Disease 0
. O 0

There O 0
were O 0
no O 0
deaths O 0
. O 0

RAPA B-Chemical 0
was O 0
discontinued O 0
in O 0
four O 0
patients O 0
, O 0
because O 0
of O 0
pneumonia B-Disease 0
in O 0
two O 0
, O 0
PTLD B-Disease 0
in O 0
one O 0
, O 0
and O 0
oral O 0
aphtous B-Disease 0
ulcers I-Disease 0
in O 0
one O 0
. O 0

RAPA B-Chemical 0
levels O 0
were O 0
high O 0
( O 0
> O 0
15 O 0
ng O 0
/ O 0
ml O 0
) O 0
in O 0
7 O 0
of O 0
13 O 0
( O 0
54 O 0
% O 0
) O 0
patients O 0
. O 0

CONCLUSIONS O 0
: O 0
RAPA B-Chemical 0
conversion O 0
provides O 0
adequate O 0
immunosuppression O 0
to O 0
enable O 0
CsA B-Chemical 0
withdrawal O 0
. O 0

However O 0
, O 0
when O 0
converting O 0
patients O 0
to O 0
RAPA B-Chemical 0
drug O 0
levels O 0
should O 0
be O 0
monitored O 0
to O 0
avoid O 0
over O 0
- O 0
immunosuppression O 0
and O 0
adequate O 0
antiviral O 0
and O 0
Pneumocystis B-Disease 0
carinii I-Disease 0
pneumonia I-Disease 0
prophylaxis O 0
should O 0
be O 0
given O 0
. O 0

Electro O 0
- O 0
oculography O 0
, O 0
electroretinography O 0
, O 0
visual O 0
evoked O 0
potentials O 0
, O 0
and O 0
multifocal O 0
electroretinography O 0
in O 0
patients O 0
with O 0
vigabatrin B-Chemical 0
- O 0
attributed O 0
visual B-Disease 0
field I-Disease 0
constriction I-Disease 0
. O 0

PURPOSE O 0
: O 0
Symptomatic O 0
visual B-Disease 0
field I-Disease 0
constriction I-Disease 0
thought O 0
to O 0
be O 0
associated O 0
with O 0
vigabatrin B-Chemical 0
has O 0
been O 0
reported O 0
. O 0

The O 0
current O 0
study O 0
investigated O 0
the O 0
visual O 0
fields O 0
and O 0
visual O 0
electrophysiology O 0
of O 0
eight O 0
patients O 0
with O 0
known O 0
vigabatrin B-Chemical 0
- O 0
attributed O 0
visual B-Disease 0
field I-Disease 0
loss I-Disease 0
, O 0
three O 0
of O 0
whom O 0
were O 0
reported O 0
previously O 0
. O 0

Six O 0
of O 0
the O 0
patients O 0
were O 0
no O 0
longer O 0
receiving O 0
vigabatrin B-Chemical 0
. O 0

METHODS O 0
: O 0
The O 0
central O 0
and O 0
peripheral O 0
fields O 0
were O 0
examined O 0
with O 0
the O 0
Humphrey O 0
Visual O 0
Field O 0
Analyzer O 0
. O 0

Full O 0
visual O 0
electrophysiology O 0
, O 0
including O 0
flash O 0
electroretinography O 0
( O 0
ERG O 0
) O 0
, O 0
pattern O 0
electroretinography O 0
, O 0
multifocal O 0
ERG O 0
using O 0
the O 0
VERIS O 0
system O 0
, O 0
electro O 0
- O 0
oculography O 0
, O 0
and O 0
flash O 0
and O 0
pattern O 0
visual O 0
evoked O 0
potentials O 0
, O 0
was O 0
undertaken O 0
. O 0

RESULTS O 0
: O 0
Seven O 0
patients O 0
showed O 0
marked O 0
visual B-Disease 0
field I-Disease 0
constriction I-Disease 0
with O 0
some O 0
sparing O 0
of O 0
the O 0
temporal O 0
visual O 0
field O 0
. O 0

The O 0
eighth O 0
exhibited O 0
concentric O 0
constriction O 0
. O 0

Most O 0
electrophysiological O 0
responses O 0
were O 0
usually O 0
just O 0
within O 0
normal O 0
limits O 0
; O 0
two O 0
patients O 0
had O 0
subnormal O 0
Arden O 0
electro O 0
- O 0
oculography O 0
indices O 0
; O 0
and O 0
one O 0
patient O 0
showed O 0
an O 0
abnormally O 0
delayed O 0
photopic O 0
b O 0
wave O 0
. O 0

However O 0
, O 0
five O 0
patients O 0
showed O 0
delayed O 0
30 O 0
- O 0
Hz O 0
flicker O 0
b O 0
waves O 0
, O 0
and O 0
seven O 0
patients O 0
showed O 0
delayed O 0
oscillatory O 0
potentials O 0
. O 0

Multifocal O 0
ERG O 0
showed O 0
abnormalities O 0
that O 0
sometimes O 0
correlated O 0
with O 0
the O 0
visual O 0
field O 0
appearance O 0
and O 0
confirmed O 0
that O 0
the O 0
deficit O 0
occurs O 0
at O 0
the O 0
retinal O 0
level O 0
. O 0

CONCLUSION O 0
: O 0
Marked O 0
visual B-Disease 0
field I-Disease 0
constriction I-Disease 0
appears O 0
to O 0
be O 0
associated O 0
with O 0
vigabatrin B-Chemical 0
therapy O 0
. O 0

The O 0
field O 0
defects O 0
and O 0
some O 0
electrophysiological O 0
abnormalities O 0
persist O 0
when O 0
vigabatrin B-Chemical 0
therapy O 0
is O 0
withdrawn O 0
. O 0

Myocardial B-Disease 0
ischemia I-Disease 0
due O 0
to O 0
coronary B-Disease 0
artery I-Disease 0
spasm I-Disease 0
during O 0
dobutamine B-Chemical 0
stress O 0
echocardiography 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
useful O 0
and O 0
safe O 0
provocation O 0
test O 0
for O 0
myocardial B-Disease 0
ischemia I-Disease 0
. O 0

Until O 0
now O 0
, O 0
the O 0
test O 0
has O 0
been O 0
focused O 0
only O 0
on O 0
the O 0
organic O 0
lesion O 0
in O 0
the O 0
coronary O 0
artery O 0
, O 0
and O 0
positive O 0
DSE O 0
has O 0
indicated O 0
the O 0
presence O 0
of O 0
significant O 0
fixed O 0
coronary B-Disease 0
artery I-Disease 0
stenosis I-Disease 0
. O 0

The O 0
aim O 0
of O 0
the O 0
present O 0
study O 0
is O 0
to O 0
examine O 0
whether O 0
myocardial B-Disease 0
ischemia I-Disease 0
due O 0
to O 0
coronary B-Disease 0
spasm I-Disease 0
is O 0
induced O 0
by O 0
dobutamine B-Chemical 0
. O 0

We O 0
performed O 0
DSE O 0
on O 0
51 O 0
patients O 0
with O 0
coronary B-Disease 0
spastic I-Disease 0
angina I-Disease 0
but O 0
without O 0
significant O 0
fixed O 0
coronary B-Disease 0
artery I-Disease 0
stenosis I-Disease 0
. O 0

All O 0
patients O 0
had O 0
anginal B-Disease 0
attacks O 0
at O 0
rest O 0
with O 0
ST O 0
elevation O 0
on O 0
the O 0
electrocardiogram O 0
( O 0
variant B-Disease 0
angina I-Disease 0
) O 0
. O 0

Coronary O 0
spasm O 0
was O 0
induced O 0
by O 0
intracoronary O 0
injection O 0
of O 0
acetylcholine B-Chemical 0
, O 0
and O 0
no O 0
fixed O 0
coronary B-Disease 0
artery I-Disease 0
stenosis I-Disease 0
was O 0
documented O 0
on O 0
angiograms O 0
in O 0
all O 0
patients O 0
. O 0

DSE O 0
was O 0
performed O 0
with O 0
intravenous O 0
dobutamine B-Chemical 0
infusion O 0
with O 0
an O 0
incremental O 0
doses O 0
of O 0
5 O 0
, O 0
10 O 0
, O 0
20 O 0
, O 0
30 O 0
, O 0
and O 0
40 O 0
microg O 0
/ O 0
kg O 0
/ O 0
min O 0
every O 0
5 O 0
minutes O 0
. O 0

Of O 0
the O 0
51 O 0
patients O 0
, O 0
7 O 0
patients O 0
showed O 0
asynergy O 0
with O 0
ST O 0
elevation O 0
. O 0

All O 0
7 O 0
patients O 0
( O 0
13 O 0
. O 0
7 O 0
% O 0
) O 0
had O 0
chest B-Disease 0
pain I-Disease 0
during O 0
asynergy O 0
, O 0
and O 0
both O 0
chest B-Disease 0
pain I-Disease 0
and O 0
electrocardiographic O 0
changes O 0
were O 0
preceded O 0
by O 0
asynergy O 0
. O 0

These O 0
findings O 0
indicate O 0
that O 0
dobutamine B-Chemical 0
can O 0
provoke O 0
coronary B-Disease 0
spasm I-Disease 0
in O 0
some O 0
patients O 0
with O 0
coronary B-Disease 0
spastic I-Disease 0
angina I-Disease 0
. O 0

When O 0
DSE O 0
is O 0
performed O 0
to O 0
evaluate O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
, O 0
not O 0
only O 0
fixed O 0
coronary B-Disease 0
stenosis I-Disease 0
, O 0
but O 0
also O 0
coronary B-Disease 0
spasm I-Disease 0
should O 0
be O 0
considered O 0
as O 0
a O 0
genesis O 0
of O 0
asynergy O 0
. O 0

Effect O 0
of O 0
intravenous O 0
metoprolol B-Chemical 0
or O 0
intravenous O 0
metoprolol B-Chemical 0
plus O 0
glucagon O 0
on O 0
dobutamine B-Chemical 0
- O 0
induced O 0
myocardial B-Disease 0
ischemia I-Disease 0
. O 0

STUDY O 0
OBJECTIVE O 0
: O 0
To O 0
determine O 0
the O 0
effect O 0
of O 0
metoprolol B-Chemical 0
on O 0
dobutamine B-Chemical 0
stress O 0
testing O 0
with O 0
technetium B-Chemical 0
- I-Chemical 0
99m I-Chemical 0
sestamibi I-Chemical 0
single O 0
- O 0
photon O 0
emission O 0
computed O 0
tomography O 0
imaging O 0
and O 0
ST O 0
- O 0
segment O 0
monitoring O 0
, O 0
and O 0
to O 0
assess O 0
the O 0
impact O 0
of O 0
intravenous O 0
glucagon O 0
on O 0
metoprolol B-Chemical 0
' O 0
s O 0
effects O 0
. O 0

DESIGN 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
trial O 0
. O 0

SETTING O 0
: O 0
Community O 0
hospital O 0
. O 0

PATIENTS O 0
: O 0
Twenty O 0
- O 0
two O 0
patients O 0
with O 0
known O 0
reversible O 0
perfusion O 0
defects O 0
. O 0

INTERVENTION O 0
: O 0
Patients O 0
underwent O 0
dobutamine B-Chemical 0
stress O 0
tests O 0
per O 0
standard O 0
protocol O 0
. O 0

Before O 0
dobutamine B-Chemical 0
was O 0
begun O 0
, O 0
no O 0
therapy O 0
was O 0
given O 0
during O 0
the O 0
first O 0
visit O 0
, O 0
and O 0
patients O 0
were O 0
randomized O 0
on O 0
subsequent O 0
visits O 0
to O 0
receive O 0
metoprolol B-Chemical 0
or O 0
metoprolol B-Chemical 0
plus O 0
glucagon O 0
1 O 0
mg O 0
. O 0

Metoprolol B-Chemical 0
was O 0
dosed O 0
to O 0
achieve O 0
a O 0
resting O 0
predobutamine B-Chemical 0
heart O 0
rate O 0
below O 0
65 O 0
beats O 0
/ O 0
minute O 0
or O 0
a O 0
total O 0
intravenous O 0
dose O 0
of O 0
20 O 0
mg O 0
. O 0

MEASUREMENTS O 0
AND O 0
MAIN O 0
RESULTS O 0
: O 0
Metoprolol B-Chemical 0
reduced O 0
maximum O 0
heart O 0
rate O 0
31 O 0
% O 0
, O 0
summed O 0
stress O 0
scores O 0
29 O 0
% O 0
, O 0
and O 0
summed O 0
difference O 0
scores O 0
43 O 0
% O 0
versus O 0
control O 0
. O 0

Metoprolol B-Chemical 0
plus O 0
glucagon O 0
also O 0
reduced O 0
the O 0
maximum O 0
heart O 0
rate O 0
29 O 0
% O 0
versus O 0
control O 0
. O 0

Summed O 0
stress O 0
and O 0
summed O 0
difference O 0
scores O 0
were O 0
not O 0
significantly O 0
reduced O 0
, O 0
although O 0
they O 0
were O 0
18 O 0
% O 0
and O 0
30 O 0
% O 0
lower O 0
, O 0
respectively O 0
, O 0
than O 0
control O 0
. O 0

No O 0
significant O 0
differences O 0
were O 0
found O 0
in O 0
any O 0
parameter O 0
between O 0
metoprolol B-Chemical 0
and O 0
metoprolol B-Chemical 0
- O 0
glucagon O 0
. O 0

CONCLUSION O 0
: O 0
During O 0
dobutamine B-Chemical 0
stress O 0
testing O 0
, O 0
metoprolol B-Chemical 0
attenuates O 0
or O 0
eliminates O 0
evidence O 0
of O 0
myocardial B-Disease 0
ischemia I-Disease 0
. O 0

Glucagon O 0
1 O 0
mg O 0
, O 0
although O 0
somewhat O 0
effective O 0
, O 0
does O 0
not O 0
correct O 0
this O 0
effect O 0
to O 0
the O 0
extent O 0
that O 0
it O 0
can O 0
be O 0
administered O 0
clinically O 0
. O 0

Evidence O 0
of O 0
functional O 0
somatotopy O 0
in O 0
GPi O 0
from O 0
results O 0
of O 0
pallidotomy 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
explore O 0
the O 0
functional O 0
anatomy O 0
of O 0
the O 0
globus O 0
pallidus O 0
internus O 0
( O 0
GPi O 0
) O 0
by O 0
studying O 0
the O 0
effects O 0
of O 0
unilateral O 0
pallidotomy O 0
on O 0
parkinsonian B-Disease 0
' O 0
off O 0
' O 0
signs O 0
and O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
( O 0
LID B-Disease 0
) O 0
. O 0

We O 0
found O 0
significant O 0
positive O 0
correlations O 0
between O 0
the O 0
preoperative O 0
levodopa B-Chemical 0
responsiveness O 0
of O 0
motor O 0
signs O 0
and O 0
the O 0
levodopa B-Chemical 0
responsiveness O 0
of O 0
scores O 0
in O 0
timed O 0
tests O 0
( O 0
Core O 0
Assessment O 0
Program O 0
for O 0
Intracerebral O 0
Transplantations O 0
) O 0
in O 0
the O 0
contralateral O 0
limbs O 0
and O 0
the O 0
improvement O 0
in O 0
these O 0
scores O 0
after O 0
surgery O 0
, O 0
whereas O 0
there O 0
was O 0
no O 0
correlation O 0
with O 0
the O 0
improvement O 0
in O 0
LID B-Disease 0
. O 0

We O 0
also O 0
found O 0
a O 0
highly O 0
significant O 0
correlation O 0
( O 0
P O 0
: O 0
< O 0
0 O 0
. O 0
0001 O 0
, O 0
r O 0
= O 0
0 O 0
. O 0
8 O 0
) O 0
between O 0
the O 0
volume O 0
of O 0
the O 0
ventral O 0
lesion O 0
in O 0
the O 0
GPi O 0
and O 0
the O 0
improvement O 0
in O 0
LID B-Disease 0
in O 0
the O 0
contralateral O 0
limbs O 0
, O 0
whereas O 0
there O 0
was O 0
no O 0
correlation O 0
between O 0
the O 0
ventral O 0
volume O 0
and O 0
the O 0
improvement O 0
in O 0
parkinsonian B-Disease 0
' O 0
off O 0
' O 0
signs O 0
. O 0

The O 0
volumes O 0
of O 0
the O 0
total O 0
lesion O 0
cylinder O 0
and O 0
the O 0
dorsal O 0
lesion O 0
did O 0
not O 0
correlate O 0
with O 0
the O 0
outcome O 0
of O 0
either O 0
dyskinesias B-Disease 0
or O 0
parkinsonian B-Disease 0
' O 0
off O 0
' O 0
signs O 0
. O 0

The O 0
differential O 0
predictive O 0
value O 0
of O 0
levodopa B-Chemical 0
responsiveness O 0
for O 0
the O 0
outcome O 0
of O 0
parkinsonian B-Disease 0
' O 0
off O 0
' O 0
signs O 0
and O 0
LID B-Disease 0
and O 0
the O 0
different O 0
correlations O 0
of O 0
ventral O 0
lesion O 0
volume O 0
with O 0
dyskinesias B-Disease 0
and O 0
parkinsonian B-Disease 0
' O 0
off O 0
' O 0
signs O 0
indicate O 0
that O 0
different O 0
anatomical O 0
or O 0
pathophysiological O 0
substrates O 0
may O 0
be O 0
responsible O 0
for O 0
the O 0
generation O 0
of O 0
parkinsonian B-Disease 0
' O 0
off O 0
' O 0
signs O 0
and O 0
dyskinesias B-Disease 0
. O 0

Whereas O 0
cells O 0
in O 0
a O 0
wider O 0
area O 0
of O 0
the O 0
GPi O 0
may O 0
be O 0
implicated O 0
in O 0
parkinsonism B-Disease 0
, O 0
the O 0
ventral O 0
GPi O 0
seems O 0
to O 0
be O 0
crucial O 0
for O 0
the O 0
manifestation O 0
of O 0
LID B-Disease 0
. O 0

We O 0
suggest O 0
that O 0
our O 0
observations O 0
are O 0
additional O 0
proof O 0
of O 0
the O 0
functional O 0
somatotopy O 0
of O 0
the O 0
systems O 0
within O 0
the O 0
GPi O 0
that O 0
mediate O 0
parkinsonism B-Disease 0
and O 0
dyskinesias B-Disease 0
, O 0
especially O 0
along O 0
the O 0
dorsoventral O 0
trajectory O 0
used O 0
in O 0
pallidotomy O 0
. O 0

The O 0
outcome O 0
of O 0
pallidotomy O 0
in O 0
which O 0
the O 0
lesion O 0
involves O 0
the O 0
ventral O 0
and O 0
dorsal O 0
GPi O 0
could O 0
be O 0
the O 0
net O 0
effect O 0
of O 0
alteration O 0
in O 0
the O 0
activity O 0
of O 0
pathways O 0
which O 0
mediate O 0
different O 0
symptoms O 0
, O 0
and O 0
hence O 0
could O 0
be O 0
variable O 0
. O 0

Screening O 0
for O 0
stimulant O 0
use O 0
in O 0
adult O 0
emergency O 0
department O 0
seizure B-Disease 0
patients 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
prevalence O 0
of O 0
positive O 0
plasma O 0
drug O 0
screening O 0
for O 0
cocaine B-Chemical 0
or O 0
amphetamine B-Chemical 0
in O 0
adult O 0
emergency O 0
department O 0
seizure B-Disease 0
patients O 0
. O 0

METHODS O 0
: O 0
This O 0
prospective O 0
study O 0
evaluated O 0
consecutive O 0
eligible O 0
seizure B-Disease 0
patients O 0
who O 0
had O 0
a O 0
plasma O 0
sample O 0
collected O 0
as O 0
part O 0
of O 0
their O 0
clinical O 0
evaluation O 0
. O 0

Plasma O 0
was O 0
tested O 0
for O 0
amphetamine B-Chemical 0
and O 0
the O 0
cocaine B-Chemical 0
metabolite O 0
benzoylecgonine B-Chemical 0
using O 0
enzyme O 0
- O 0
mediated O 0
immunoassay O 0
methodology O 0
. O 0

Plasma O 0
samples O 0
with O 0
benzoylecgonine B-Chemical 0
greater O 0
than O 0
150 O 0
ng O 0
/ O 0
mL O 0
or O 0
an O 0
amphetamine B-Chemical 0
greater O 0
than O 0
500 O 0
ng O 0
/ O 0
mL O 0
were O 0
defined O 0
as O 0
positive O 0
. O 0

Patient O 0
demographics O 0
, O 0
history O 0
of O 0
underlying O 0
drug O 0
or O 0
alcohol B-Chemical 0
- O 0
related O 0
seizure B-Disease 0
disorder O 0
, O 0
estimated O 0
time O 0
from O 0
seizure B-Disease 0
to O 0
sample O 0
collection O 0
, O 0
history O 0
or O 0
suspicion O 0
of O 0
cocaine B-Disease 0
or I-Disease 0
amphetamine I-Disease 0
abuse I-Disease 0
, O 0
results O 0
of O 0
clinical O 0
urine O 0
testing O 0
for O 0
drugs O 0
of O 0
abuse O 0
, O 0
and O 0
assay O 0
results O 0
were O 0
recorded O 0
without O 0
patient O 0
identifiers O 0
. O 0

RESULTS O 0
: O 0
Fourteen O 0
of O 0
248 O 0
( O 0
5 O 0
. O 0
6 O 0
% O 0
, O 0
95 O 0
% O 0
CI O 0
2 O 0
. O 0
7 O 0
% O 0
- O 0
8 O 0
. O 0
5 O 0
% O 0
) O 0
plasma O 0
samples O 0
were O 0
positive O 0
by O 0
immunoassay O 0
testing O 0
for O 0
benzoylecgonine B-Chemical 0
and O 0
no O 0
samples O 0
( O 0
0 O 0
% O 0
, O 0
95 O 0
% O 0
CI O 0
0 O 0
- O 0
1 O 0
. O 0
2 O 0
% O 0
) O 0
were O 0
positive O 0
for O 0
amphetamine B-Chemical 0
. O 0

Positive O 0
test O 0
results O 0
were O 0
more O 0
common O 0
in O 0
patient O 0
visits O 0
where O 0
there O 0
was O 0
a O 0
history O 0
or O 0
suspicion O 0
of O 0
cocaine B-Disease 0
or I-Disease 0
amphetamine I-Disease 0
abuse I-Disease 0
( O 0
p O 0
< O 0
0 O 0
. O 0
0005 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
During O 0
this O 0
study O 0
period O 0
, O 0
routine O 0
plasma O 0
screening O 0
for O 0
cocaine B-Chemical 0
and O 0
amphetamines B-Chemical 0
in O 0
adult O 0
seizure B-Disease 0
patients O 0
had O 0
a O 0
low O 0
yield O 0
. O 0

As O 0
a O 0
result O 0
, O 0
routine O 0
plasma O 0
screening O 0
would O 0
yield O 0
few O 0
cases O 0
of O 0
stimulant O 0
drug O 0
in O 0
which O 0
there O 0
was O 0
neither O 0
a O 0
history O 0
nor O 0
suspicion O 0
of O 0
drug B-Disease 0
abuse I-Disease 0
in O 0
this O 0
population O 0
. O 0

Contribution O 0
of O 0
sodium B-Chemical 0
valproate I-Chemical 0
to 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

We O 0
report O 0
the O 0
case O 0
of O 0
a O 0
62 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
who O 0
was O 0
administered O 0
sodium B-Chemical 0
valproate I-Chemical 0
( O 0
VPA B-Chemical 0
) O 0
and O 0
who O 0
subsequently O 0
developed 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
SIADH B-Disease 0
) O 0
. O 0

He O 0
had O 0
been O 0
taking O 0
VPA B-Chemical 0
for O 0
treatment O 0
of O 0
idiopathic O 0
generalized O 0
tonic B-Disease 0
- I-Disease 0
clonic I-Disease 0
convulsions I-Disease 0
since O 0
he O 0
was O 0
56 O 0
years O 0
old O 0
. O 0

After O 0
substituting O 0
VPA B-Chemical 0
with O 0
zonisamide B-Chemical 0
, O 0
the O 0
serum O 0
sodium B-Chemical 0
level O 0
returned O 0
to O 0
normal O 0
. O 0

We O 0
consider O 0
this O 0
episode O 0
of O 0
SIADH B-Disease 0
to O 0
be O 0
the O 0
result O 0
of O 0
a O 0
combination O 0
of O 0
factors O 0
including O 0
a O 0
weakness B-Disease 0
of I-Disease 0
the I-Disease 0
central I-Disease 0
nervous I-Disease 0
system I-Disease 0
and O 0
the O 0
long O 0
- O 0
term O 0
administration O 0
of O 0
VPA B-Chemical 0
. O 0

Association O 0
of O 0
nitric B-Chemical 0
oxide I-Chemical 0
production O 0
and O 0
apoptosis O 0
in O 0
a O 0
model O 0
of O 0
experimental O 0
nephropathy B-Disease 0
. O 0

BACKGROUND O 0
: O 0
In O 0
recent O 0
studies O 0
increased O 0
amounts O 0
of O 0
nitric B-Chemical 0
oxide I-Chemical 0
( O 0
NO B-Chemical 0
) O 0
and O 0
apoptosis O 0
have O 0
been O 0
implicated O 0
in O 0
various O 0
pathological O 0
conditions O 0
in O 0
the O 0
kidney O 0
. O 0

We O 0
have O 0
studied O 0
the O 0
role O 0
of O 0
NO B-Chemical 0
and O 0
its O 0
association O 0
with O 0
apoptosis O 0
in O 0
an O 0
experimental O 0
model O 0
of O 0
nephrotic B-Disease 0
syndrome I-Disease 0
induced O 0
by O 0
a O 0
single O 0
injection O 0
of O 0
adriamycin B-Chemical 0
( O 0
ADR B-Chemical 0
) O 0
. O 0

METHODS O 0
: O 0
The O 0
alteration O 0
in O 0
the O 0
NO B-Chemical 0
pathway O 0
was O 0
assessed O 0
by O 0
measuring O 0
nitrite B-Chemical 0
levels O 0
in O 0
serum O 0
/ O 0
urine O 0
and O 0
by O 0
evaluating O 0
the O 0
changes O 0
in O 0
vascular O 0
reactivity O 0
of O 0
the O 0
isolated O 0
perfused O 0
rat O 0
kidney O 0
( O 0
IPRK O 0
) O 0
system O 0
. O 0

Rats O 0
were O 0
stratified O 0
into O 0
control O 0
groups O 0
and O 0
ADR B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
groups O 0
. O 0

These O 0
two O 0
groups O 0
were O 0
then O 0
divided O 0
into O 0
: O 0
group O 0
1 O 0
, O 0
animals O 0
receiving O 0
saline O 0
; O 0
and O 0
group O 0
2 O 0
, O 0
animals O 0
receiving O 0
aminoguanidine B-Chemical 0
( O 0
AG B-Chemical 0
) O 0
which O 0
is O 0
a O 0
specific O 0
inhibitor O 0
of O 0
inducible O 0
- O 0
NO B-Chemical 0
synthase O 0
. O 0

On O 0
day O 0
21 O 0
, O 0
rats O 0
were O 0
sacrificed O 0
after O 0
obtaining O 0
material O 0
for O 0
biochemical O 0
analysis O 0
. O 0

RESULTS O 0
: O 0
Histopathological O 0
examination O 0
of O 0
the O 0
kidneys O 0
of O 0
rats O 0
treated O 0
with O 0
ADR B-Chemical 0
revealed O 0
focal O 0
areas O 0
of O 0
mesangial B-Disease 0
proliferation I-Disease 0
and O 0
mild O 0
tubulointerstitial B-Disease 0
inflammation I-Disease 0
. O 0

They O 0
also O 0
had O 0
significantly O 0
higher O 0
levels O 0
of O 0
proteinuria B-Disease 0
compared O 0
with O 0
control O 0
and O 0
treatment O 0
groups O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Urine O 0
nitrite B-Chemical 0
levels O 0
were O 0
significantly O 0
increased O 0
in O 0
the O 0
ADR B-Chemical 0
- O 0
nephropathy B-Disease 0
group O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

In O 0
the O 0
IPRK O 0
phenylephrine B-Chemical 0
and O 0
acetylcholine B-Chemical 0
related O 0
responses O 0
were O 0
significantly O 0
impaired O 0
in O 0
the O 0
ADR B-Chemical 0
- O 0
nephropathy B-Disease 0
group O 0
. O 0

Apoptosis O 0
was O 0
not O 0
detected O 0
in O 0
controls O 0
. O 0

However O 0
, O 0
in O 0
the O 0
ADR B-Chemical 0
- O 0
nephropathy B-Disease 0
group O 0
, O 0
numerous O 0
apoptotic O 0
cells O 0
were O 0
identified O 0
in O 0
the O 0
tubulointerstitial O 0
areas O 0
. O 0

Double O 0
staining O 0
revealed O 0
numerous O 0
interstitial O 0
apoptotic O 0
cells O 0
to O 0
stain O 0
for O 0
ED1 O 0
, O 0
a O 0
marker O 0
for O 0
monocytes O 0
/ O 0
macrophages O 0
. O 0

Treatment O 0
with O 0
AG B-Chemical 0
prevented O 0
the O 0
impairment O 0
of O 0
renal O 0
vascular O 0
bed O 0
responses O 0
and O 0
reduced O 0
both O 0
urine O 0
nitrite B-Chemical 0
levels O 0
and O 0
apoptosis O 0
to O 0
control O 0
levels O 0
. O 0

CONCLUSION O 0
: O 0
We O 0
suggest O 0
that O 0
interactions O 0
between O 0
NO B-Chemical 0
and O 0
apoptosis O 0
are O 0
important O 0
in O 0
the O 0
pathogenesis O 0
of O 0
the O 0
ADR B-Chemical 0
- O 0
induced O 0
nephrosis B-Disease 0
. O 0

Dual O 0
effects O 0
of O 0
melatonin B-Chemical 0
on O 0
barbiturate B-Chemical 0
- O 0
induced O 0
narcosis B-Disease 0
in O 0
rats O 0
. O 0

Melatonin B-Chemical 0
affects O 0
the O 0
circadian O 0
sleep O 0
/ O 0
wake O 0
cycle O 0
, O 0
but O 0
it O 0
is O 0
not O 0
clear O 0
whether O 0
it O 0
may O 0
influence O 0
drug O 0
- O 0
induced O 0
narcosis B-Disease 0
. O 0

Sodium B-Chemical 0
thiopenthal I-Chemical 0
was O 0
administered O 0
intraperitoneally O 0
into O 0
male O 0
rats O 0
pre O 0
- O 0
treated O 0
with O 0
melatonin B-Chemical 0
( O 0
0 O 0
. O 0
05 O 0
, O 0
0 O 0
. O 0
5 O 0
, O 0
5 O 0
and O 0
50 O 0
mg O 0
/ O 0
kg O 0
) O 0
. O 0

Melatonin B-Chemical 0
pre O 0
- O 0
treatment O 0
affected O 0
in O 0
a O 0
dual O 0
manner O 0
barbiturate B-Chemical 0
narcosis B-Disease 0
, O 0
however O 0
, O 0
no O 0
dose O 0
- O 0
effect O 0
correlation O 0
was O 0
found O 0
. O 0

In O 0
particular O 0
, O 0
low O 0
doses O 0
reduced O 0
the O 0
latency O 0
to O 0
and O 0
prolonged O 0
the O 0
duration O 0
of O 0
barbiturate B-Chemical 0
narcosis B-Disease 0
. O 0

In O 0
contrast O 0
, O 0
the O 0
highest O 0
dose O 0
of O 0
melatonin B-Chemical 0
( O 0
50 O 0
mg O 0
/ O 0
kg O 0
) O 0
caused O 0
a O 0
paradoxical O 0
increase O 0
in O 0
the O 0
latency O 0
and O 0
produced O 0
a O 0
sustained O 0
reduction O 0
of O 0
the O 0
duration O 0
of O 0
narcosis B-Disease 0
, O 0
and O 0
a O 0
reduction O 0
in O 0
mortality O 0
rate O 0
. O 0

Melatonin B-Chemical 0
0 O 0
. O 0
5 O 0
and O 0
5 O 0
mg O 0
/ O 0
kg O 0
influenced O 0
the O 0
duration O 0
but O 0
not O 0
the O 0
latency O 0
of O 0
ketamine B-Chemical 0
- O 0
or O 0
diazepam B-Chemical 0
- O 0
induced O 0
narcosis B-Disease 0
. O 0

Thus O 0
, O 0
the O 0
dual O 0
action O 0
of O 0
melatonin B-Chemical 0
on O 0
pharmacological O 0
narcosis B-Disease 0
seems O 0
to O 0
be O 0
specific O 0
for O 0
the O 0
barbiturate B-Chemical 0
mechanism O 0
of O 0
action O 0
. O 0

Reduced O 0
cardiotoxicity B-Disease 0
and O 0
preserved O 0
antitumor O 0
efficacy O 0
of O 0
liposome O 0
- O 0
encapsulated O 0
doxorubicin B-Chemical 0
and O 0
cyclophosphamide B-Chemical 0
compared O 0
with O 0
conventional O 0
doxorubicin B-Chemical 0
and O 0
cyclophosphamide B-Chemical 0
in O 0
a O 0
randomized O 0
, O 0
multicenter O 0
trial O 0
of O 0
metastatic O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

PURPOSE O 0
: O 0
To O 0
determine O 0
whether O 0
Myocet B-Chemical 0
( O 0
liposome O 0
- O 0
encapsulated O 0
doxorubicin B-Chemical 0
; O 0
The O 0
Liposome O 0
Company O 0
, O 0
Elan O 0
Corporation O 0
, O 0
Princeton O 0
, O 0
NJ O 0
) O 0
in O 0
combination O 0
with O 0
cyclophosphamide B-Chemical 0
significantly O 0
reduces O 0
doxorubicin B-Chemical 0
cardiotoxicity B-Disease 0
while O 0
providing O 0
comparable O 0
antitumor O 0
efficacy O 0
in O 0
first O 0
- O 0
line O 0
treatment O 0
of O 0
metastatic O 0
breast B-Disease 0
cancer I-Disease 0
( O 0
MBC B-Disease 0
) O 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
Two O 0
hundred O 0
ninety O 0
- O 0
seven O 0
patients O 0
with O 0
MBC B-Disease 0
and O 0
no O 0
prior O 0
chemotherapy O 0
for O 0
metastatic O 0
disease O 0
were O 0
randomized O 0
to O 0
receive O 0
either O 0
60 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
of O 0
Myocet B-Chemical 0
( O 0
M O 0
) O 0
or O 0
conventional O 0
doxorubicin B-Chemical 0
( O 0
A O 0
) O 0
, O 0
in O 0
combination O 0
with O 0
600 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
of O 0
cyclophosphamide B-Chemical 0
( O 0
C O 0
) O 0
, O 0
every O 0
3 O 0
weeks O 0
until O 0
disease O 0
progression O 0
or O 0
unacceptable O 0
toxicity B-Disease 0
. O 0

Cardiotoxicity B-Disease 0
was O 0
defined O 0
by O 0
reductions O 0
in O 0
left O 0
- O 0
ventricular O 0
ejection O 0
fraction O 0
, O 0
assessed O 0
by O 0
serial O 0
multigated O 0
radionuclide O 0
angiography O 0
scans O 0
, O 0
or O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
( O 0
CHF B-Disease 0
) O 0
. O 0

Antitumor O 0
efficacy O 0
was O 0
assessed O 0
by O 0
objective O 0
tumor B-Disease 0
response O 0
rates O 0
( O 0
World O 0
Health O 0
Organization O 0
criteria O 0
) O 0
, O 0
time O 0
to O 0
progression O 0
, O 0
and O 0
survival O 0
. O 0

RESULTS O 0
: O 0
Six O 0
percent O 0
of O 0
MC O 0
patients O 0
versus O 0
21 O 0
% O 0
( O 0
including O 0
five O 0
cases O 0
of O 0
CHF B-Disease 0
) O 0
of O 0
AC O 0
patients O 0
developed O 0
cardiotoxicity B-Disease 0
( O 0
P O 0
= O 0
. O 0
0002 O 0
) O 0
. O 0

Median O 0
cumulative O 0
doxorubicin B-Chemical 0
dose O 0
at O 0
onset O 0
was O 0
more O 0
than O 0
2 O 0
, O 0
220 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
for O 0
MC O 0
versus O 0
480 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
for O 0
AC O 0
( O 0
P O 0
= O 0
. O 0
0001 O 0
, O 0
hazard O 0
ratio O 0
, O 0
5 O 0
. O 0
04 O 0
) O 0
. O 0

MC O 0
patients O 0
also O 0
experienced O 0
less O 0
grade O 0
4 O 0
neutropenia B-Disease 0
. O 0

Antitumor O 0
efficacy O 0
of O 0
MC O 0
versus O 0
AC O 0
was O 0
comparable O 0
: O 0
objective O 0
response O 0
rates O 0
, O 0
43 O 0
% O 0
versus O 0
43 O 0
% O 0
; O 0
median O 0
time O 0
to O 0
progression O 0
, O 0
5 O 0
. O 0
1 O 0
% O 0
versus O 0
5 O 0
. O 0
5 O 0
months O 0
; O 0
median O 0
time O 0
to O 0
treatment O 0
failure O 0
, O 0
4 O 0
. O 0
6 O 0
versus O 0
4 O 0
. O 0
4 O 0
months O 0
; O 0
and O 0
median O 0
survival O 0
, O 0
19 O 0
versus O 0
16 O 0
months O 0
. O 0

CONCLUSION O 0
: O 0
Myocet B-Chemical 0
improves O 0
the O 0
therapeutic O 0
index O 0
of O 0
doxorubicin B-Chemical 0
by O 0
significantly O 0
reducing O 0
cardiotoxicity B-Disease 0
and O 0
grade O 0
4 O 0
neutropenia B-Disease 0
and O 0
provides O 0
comparable O 0
antitumor O 0
efficacy O 0
, O 0
when O 0
used O 0
in O 0
combination O 0
with O 0
cyclophosphamide B-Chemical 0
as O 0
first O 0
- O 0
line O 0
therapy O 0
for O 0
MBC B-Disease 0
. O 0

The O 0
role O 0
of O 0
nitrergic O 0
system O 0
in O 0
lidocaine B-Chemical 0
- O 0
induced O 0
convulsion B-Disease 0
in O 0
the O 0
mouse O 0
. O 0

The O 0
effects O 0
of O 0
N B-Chemical 0
- I-Chemical 0
nitro I-Chemical 0
- I-Chemical 0
L I-Chemical 0
- I-Chemical 0
arginine I-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
ester I-Chemical 0
( O 0
L B-Chemical 0
- I-Chemical 0
NAME I-Chemical 0
) O 0
a O 0
nitric B-Chemical 0
oxide I-Chemical 0
( O 0
NO B-Chemical 0
) O 0
synthase O 0
inhibitor O 0
and O 0
L B-Chemical 0
- I-Chemical 0
arginine I-Chemical 0
, O 0
a O 0
NO B-Chemical 0
precursor O 0
, O 0
were O 0
investigated O 0
on O 0
lidocaine B-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
. O 0

In O 0
the O 0
first O 0
experiment O 0
, O 0
four O 0
groups O 0
of O 0
mice O 0
received O 0
physiological O 0
saline O 0
( O 0
0 O 0
. O 0
9 O 0
% O 0
) O 0
, O 0
L B-Chemical 0
- I-Chemical 0
arginine I-Chemical 0
( O 0
300 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
L B-Chemical 0
- I-Chemical 0
NAME I-Chemical 0
( O 0
100 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
and O 0
diazepam B-Chemical 0
( O 0
2 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
respectively O 0
. O 0

Thirty O 0
minutes O 0
after O 0
these O 0
injections O 0
, O 0
all O 0
mice O 0
received O 0
lidocaine B-Chemical 0
( O 0
50 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

In O 0
the O 0
second O 0
experiment O 0
, O 0
four O 0
groups O 0
of O 0
mice O 0
received O 0
similar O 0
treatment O 0
in O 0
the O 0
first O 0
experiment O 0
, O 0
and O 0
30 O 0
min O 0
after O 0
these O 0
injections O 0
, O 0
all O 0
mice O 0
received O 0
a O 0
higher O 0
dose O 0
of O 0
lidocaine B-Chemical 0
( O 0
80 O 0
mg O 0
/ O 0
kg O 0
) O 0
. O 0

L B-Chemical 0
- I-Chemical 0
NAME I-Chemical 0
( O 0
100 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
and O 0
diazepam B-Chemical 0
( O 0
2 O 0
mg O 0
/ O 0
kg O 0
) O 0
significantly O 0
decreased O 0
the O 0
incidence O 0
of O 0
lidocaine B-Chemical 0
( O 0
50 O 0
mg O 0
/ O 0
kg O 0
) O 0
- O 0
induced O 0
convulsions B-Disease 0
. O 0

In O 0
contrast O 0
, O 0
the O 0
L B-Chemical 0
- I-Chemical 0
arginine I-Chemical 0
treatment O 0
increased O 0
the O 0
incidence O 0
of O 0
lidocaine B-Chemical 0
( O 0
80 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
induced O 0
convulsions B-Disease 0
significantly O 0
. O 0

These O 0
results O 0
may O 0
suggest O 0
that O 0
NO B-Chemical 0
is O 0
a O 0
proconvulsant O 0
mediator O 0
in O 0
lidocaine B-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
. O 0

Erythropoietin O 0
restores O 0
the O 0
anemia B-Disease 0
- O 0
induced O 0
reduction O 0
in O 0
cyclophosphamide B-Chemical 0
cytotoxicity B-Disease 0
in O 0
rat O 0
tumors B-Disease 0
. O 0

The O 0
aim O 0
of O 0
this O 0
study O 0
was O 0
to O 0
examine O 0
the O 0
impact O 0
of O 0
anemia B-Disease 0
prevention O 0
by O 0
recombinant O 0
human O 0
erythropoietin O 0
( O 0
rHuEPO O 0
) O 0
treatment O 0
on O 0
the O 0
cytotoxicity B-Disease 0
of O 0
cyclophosphamide B-Chemical 0
in O 0
solid O 0
experimental O 0
tumors B-Disease 0
. O 0

Anemia B-Disease 0
was O 0
induced O 0
using O 0
a O 0
single O 0
dose O 0
of O 0
carboplatin B-Chemical 0
( O 0
50 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
) O 0
resulting O 0
in O 0
a O 0
long O 0
- O 0
lasting O 0
reduction O 0
( O 0
30 O 0
% O 0
) O 0
of O 0
the O 0
hemoglobin O 0
concentration O 0
. O 0

In O 0
a O 0
second O 0
group O 0
, O 0
the O 0
development O 0
of O 0
anemia B-Disease 0
was O 0
prevented O 0
by O 0
rHuEPO O 0
( O 0
1000 O 0
IU O 0
/ O 0
kg O 0
) O 0
administered O 0
s O 0
. O 0
c O 0
. O 0
three O 0
times O 0
/ O 0
week O 0
starting O 0
7 O 0
days O 0
before O 0
carboplatin B-Chemical 0
application O 0
. O 0

Four O 0
days O 0
after O 0
carboplatin B-Chemical 0
treatment O 0
, O 0
tumors B-Disease 0
( O 0
DS O 0
- O 0
sarcoma B-Disease 0
of O 0
the O 0
rat O 0
) O 0
were O 0
implanted O 0
s O 0
. O 0
c O 0
. O 0
onto O 0
the O 0
hind O 0
food O 0
dorsum O 0
. O 0

Neither O 0
carboplatin B-Chemical 0
nor O 0
rHuEPO O 0
treatment O 0
influenced O 0
tumor B-Disease 0
growth O 0
rate O 0
per O 0
se O 0
. O 0

When O 0
tumors B-Disease 0
were O 0
treated O 0
with O 0
a O 0
single O 0
dose O 0
of O 0
cyclophosphamide B-Chemical 0
( O 0
60 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
5 O 0
days O 0
after O 0
implantation O 0
, O 0
a O 0
growth O 0
delay O 0
with O 0
a O 0
subsequent O 0
regrowth O 0
of O 0
the O 0
tumors B-Disease 0
was O 0
observed O 0
. O 0

In O 0
the O 0
anemia B-Disease 0
group O 0
, O 0
the O 0
growth O 0
delay O 0
was O 0
significantly O 0
shorter O 0
compared O 0
with O 0
nonanemic O 0
controls O 0
( O 0
13 O 0
. O 0
3 O 0
days O 0
versus O 0
8 O 0
. O 0
6 O 0
days O 0
) O 0
. O 0

In O 0
the O 0
group O 0
where O 0
anemia B-Disease 0
was O 0
prevented O 0
by O 0
rHuEPO O 0
treatment O 0
, O 0
growth O 0
delay O 0
was O 0
comparable O 0
with O 0
that O 0
of O 0
nonanemic O 0
controls O 0
( O 0
13 O 0
. O 0
3 O 0
days O 0
) O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
chemotherapy O 0
- O 0
induced O 0
anemia B-Disease 0
reduces O 0
cytotoxicity B-Disease 0
of O 0
cyclophosphamide B-Chemical 0
in O 0
tumors B-Disease 0
, O 0
whereas O 0
correction O 0
of O 0
anemia B-Disease 0
by O 0
rHuEPO O 0
treatment O 0
( O 0
epoetin O 0
alpha O 0
) O 0
increases O 0
the O 0
sensitivity O 0
, O 0
probably O 0
as O 0
a O 0
result O 0
of O 0
an O 0
improved O 0
oxygen B-Chemical 0
supply O 0
to O 0
tumor B-Disease 0
tissue O 0
. O 0

Fatal O 0
haemorrhagic B-Disease 0
myocarditis I-Disease 0
secondary O 0
to O 0
cyclophosphamide B-Chemical 0
therapy O 0
. O 0

Haemorrhagic B-Disease 0
myocarditis I-Disease 0
is O 0
a O 0
rare O 0
but O 0
important O 0
complication O 0
of O 0
cyclophosphamide B-Chemical 0
therapy O 0
. O 0

Echocardiographic O 0
identification O 0
of O 0
the O 0
disorder O 0
can O 0
be O 0
made O 0
. O 0

We O 0
believe O 0
that O 0
the O 0
ultrasound O 0
features O 0
of O 0
this O 0
disorder O 0
have O 0
not O 0
been O 0
previously O 0
reported O 0
. O 0

Effects O 0
of O 0
verapamil B-Chemical 0
on O 0
atrial B-Disease 0
fibrillation I-Disease 0
and O 0
its O 0
electrophysiological O 0
determinants O 0
in O 0
dogs O 0
. O 0

BACKGROUND O 0
: O 0
Atrial B-Disease 0
tachycardia I-Disease 0
- O 0
induced O 0
remodeling O 0
promotes O 0
the O 0
occurrence O 0
and O 0
maintenance O 0
of O 0
atrial B-Disease 0
fibrillation I-Disease 0
( O 0
AF B-Disease 0
) O 0
and O 0
decreases O 0
L O 0
- O 0
type O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
current O 0
. O 0

There O 0
is O 0
also O 0
a O 0
clinical O 0
suggestion O 0
that O 0
acute O 0
L O 0
- O 0
type O 0
Ca B-Chemical 0
( O 0
2 O 0
) O 0
channel O 0
blockade O 0
can O 0
promote O 0
AF B-Disease 0
, O 0
consistent O 0
with O 0
an O 0
AF B-Disease 0
promoting O 0
effect O 0
of O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
channel O 0
inhibition O 0
. O 0

METHODS O 0
: O 0
To O 0
evaluate O 0
the O 0
potential O 0
mechanisms O 0
of O 0
AF B-Disease 0
promotion O 0
by O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
channel O 0
blockers O 0
, O 0
we O 0
administered O 0
verapamil B-Chemical 0
to O 0
morphine B-Chemical 0
- O 0
chloralose B-Chemical 0
anesthetized O 0
dogs O 0
. O 0

Diltiazem B-Chemical 0
was O 0
used O 0
as O 0
a O 0
comparison O 0
drug O 0
and O 0
autonomic O 0
blockade O 0
with O 0
atropine B-Chemical 0
and O 0
nadolol B-Chemical 0
was O 0
applied O 0
in O 0
some O 0
experiments O 0
. O 0

Epicardial O 0
mapping O 0
with O 0
240 O 0
epicardial O 0
electrodes O 0
was O 0
used O 0
to O 0
evaluate O 0
activation O 0
during O 0
AF B-Disease 0
. O 0

RESULTS O 0
: O 0
Verapamil B-Chemical 0
caused O 0
AF B-Disease 0
promotion O 0
in O 0
six O 0
dogs O 0
, O 0
increasing O 0
mean O 0
duration O 0
of O 0
AF B-Disease 0
induced O 0
by O 0
burst O 0
pacing O 0
, O 0
from O 0
8 O 0
+ O 0
/ O 0
- O 0
4 O 0
s O 0
( O 0
mean O 0
+ O 0
/ O 0
- O 0
S O 0
. O 0
E O 0
. O 0
) O 0
to O 0
95 O 0
+ O 0
/ O 0
- O 0
39 O 0
s O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
vs O 0
. O 0
control O 0
) O 0
at O 0
a O 0
loading O 0
dose O 0
of O 0
0 O 0
. O 0
1 O 0
mg O 0
/ O 0
kg O 0
and O 0
228 O 0
+ O 0
/ O 0
- O 0
101 O 0
s O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
0005 O 0
vs O 0
. O 0
control O 0
) O 0
at O 0
a O 0
dose O 0
of O 0
0 O 0
. O 0
2 O 0
mg O 0
/ O 0
kg O 0
. O 0

Underlying O 0
electrophysiological O 0
mechanisms O 0
were O 0
studied O 0
in O 0
detail O 0
in O 0
five O 0
additional O 0
dogs O 0
under O 0
control O 0
conditions O 0
and O 0
in O 0
the O 0
presence O 0
of O 0
the O 0
higher O 0
dose O 0
of O 0
verapamil B-Chemical 0
. O 0

In O 0
these O 0
experiments O 0
, O 0
verapamil B-Chemical 0
shortened O 0
mean O 0
effective O 0
refractory O 0
period O 0
( O 0
ERP O 0
) O 0
from O 0
122 O 0
+ O 0
/ O 0
- O 0
5 O 0
to O 0
114 O 0
+ O 0
/ O 0
- O 0
4 O 0
ms O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
02 O 0
) O 0
at O 0
a O 0
cycle O 0
length O 0
of O 0
300 O 0
ms O 0
, O 0
decreased O 0
ERP O 0
heterogeneity O 0
( O 0
from O 0
15 O 0
+ O 0
/ O 0
- O 0
1 O 0
to O 0
10 O 0
+ O 0
/ O 0
- O 0
1 O 0
% O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
, O 0
heterogeneously O 0
accelerated O 0
atrial O 0
conduction O 0
and O 0
decreased O 0
the O 0
cycle O 0
length O 0
of O 0
AF B-Disease 0
( O 0
94 O 0
+ O 0
/ O 0
- O 0
4 O 0
to O 0
84 O 0
+ O 0
/ O 0
- O 0
3 O 0
ms O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
005 O 0
) O 0
. O 0

Diltiazem B-Chemical 0
did O 0
not O 0
affect O 0
ERP O 0
, O 0
AF B-Disease 0
cycle O 0
length O 0
or O 0
AF B-Disease 0
duration O 0
, O 0
but O 0
produced O 0
conduction O 0
acceleration O 0
similar O 0
to O 0
that O 0
caused O 0
by O 0
verapamil B-Chemical 0
( O 0
n O 0
= O 0
5 O 0
) O 0
. O 0

In O 0
the O 0
presence O 0
of O 0
autonomic O 0
blockade O 0
, O 0
verapamil B-Chemical 0
failed O 0
to O 0
promote O 0
AF B-Disease 0
and O 0
increased O 0
, O 0
rather O 0
than O 0
decreasing O 0
, O 0
refractoriness O 0
. O 0

Neither O 0
verapamil B-Chemical 0
nor O 0
diltiazem B-Chemical 0
affected O 0
atrial O 0
conduction O 0
in O 0
the O 0
presence O 0
of O 0
autonomic O 0
blockade O 0
. O 0

Epicardial O 0
mapping O 0
suggested O 0
that O 0
verapamil B-Chemical 0
promoted O 0
AF B-Disease 0
by O 0
increasing O 0
the O 0
number O 0
of O 0
simultaneous O 0
wavefronts O 0
reflected O 0
by O 0
separate O 0
zones O 0
of O 0
reactivation O 0
in O 0
each O 0
cycle O 0
. O 0

CONCLUSIONS O 0
: O 0
Verapamil B-Chemical 0
promotes O 0
AF B-Disease 0
in O 0
normal O 0
dogs O 0
by O 0
promoting O 0
multiple O 0
circuit O 0
reentry O 0
, O 0
an O 0
effect O 0
dependent O 0
on O 0
intact O 0
autonomic O 0
tone O 0
and O 0
not O 0
shared O 0
by O 0
diltiazem B-Chemical 0
. O 0

Calcitonin O 0
gene O 0
- O 0
related O 0
peptide O 0
levels O 0
during O 0
nitric B-Chemical 0
oxide I-Chemical 0
- O 0
induced O 0
headache B-Disease 0
in O 0
patients O 0
with O 0
chronic O 0
tension B-Disease 0
- I-Disease 0
type I-Disease 0
headache I-Disease 0
. O 0

It O 0
has O 0
been O 0
proposed O 0
that O 0
nitric B-Chemical 0
oxide I-Chemical 0
( O 0
NO B-Chemical 0
) O 0
induced O 0
headache B-Disease 0
in O 0
primary B-Disease 0
headaches I-Disease 0
may O 0
be O 0
associated O 0
with O 0
release O 0
of O 0
calcitonin O 0
gene O 0
- O 0
related O 0
peptide O 0
( O 0
CGRP O 0
) O 0
. O 0

In O 0
the O 0
present O 0
study O 0
we O 0
aimed O 0
to O 0
investigate O 0
plasma O 0
levels O 0
of O 0
CGRP O 0
during O 0
headache B-Disease 0
induced O 0
by O 0
the O 0
NO B-Chemical 0
donor O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
( O 0
GTN B-Chemical 0
) O 0
in O 0
16 O 0
patients O 0
with O 0
chronic O 0
tension B-Disease 0
- I-Disease 0
type I-Disease 0
headache I-Disease 0
and O 0
16 O 0
healthy O 0
controls O 0
. O 0

The O 0
subjects O 0
were O 0
randomly O 0
allocated O 0
to O 0
receive O 0
0 O 0
. O 0
5 O 0
microg O 0
/ O 0
kg O 0
/ O 0
min O 0
GTN B-Chemical 0
or O 0
placebo O 0
over O 0
20 O 0
min O 0
on O 0
two O 0
headache B-Disease 0
- O 0
free O 0
days O 0
. O 0

Blood O 0
samples O 0
were O 0
collected O 0
at O 0
baseline O 0
, O 0
10 O 0
, O 0
20 O 0
and O 0
60 O 0
min O 0
after O 0
start O 0
of O 0
infusion O 0
. O 0

Both O 0
patients O 0
and O 0
controls O 0
developed O 0
significantly O 0
stronger O 0
immediate O 0
headache B-Disease 0
on O 0
the O 0
GTN B-Chemical 0
day O 0
than O 0
on O 0
the O 0
placebo O 0
day O 0
and O 0
the O 0
headache B-Disease 0
was O 0
significantly O 0
more O 0
pronounced O 0
in O 0
patients O 0
than O 0
in O 0
controls O 0
. O 0

There O 0
was O 0
no O 0
difference O 0
between O 0
the O 0
area O 0
under O 0
the O 0
CGRP O 0
curve O 0
( O 0
AUCCGRP O 0
) O 0
on O 0
GTN B-Chemical 0
vs O 0
. O 0
placebo O 0
day O 0
in O 0
either O 0
patients O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
65 O 0
) O 0
or O 0
controls O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
48 O 0
) O 0
. O 0

The O 0
AUCCGRP O 0
recorded O 0
on O 0
the O 0
GTN B-Chemical 0
day O 0
did O 0
not O 0
differ O 0
between O 0
patients O 0
and O 0
controls O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
36 O 0
) O 0
. O 0

Both O 0
in O 0
patients O 0
and O 0
controls O 0
, O 0
CGRP O 0
levels O 0
changed O 0
significantly O 0
over O 0
time O 0
, O 0
on O 0
both O 0
the O 0
GTN B-Chemical 0
and O 0
placebo O 0
days O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

The O 0
present O 0
study O 0
indicates O 0
that O 0
NO B-Chemical 0
- O 0
induced O 0
immediate O 0
headache B-Disease 0
is O 0
not O 0
associated O 0
with O 0
release O 0
of O 0
CGRP O 0
. O 0

Fluconazole B-Chemical 0
- O 0
induced O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
present O 0
a O 0
case O 0
of O 0
fluconazole B-Chemical 0
- O 0
associated O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
( O 0
TDP B-Disease 0
) O 0
and O 0
discuss O 0
fluconazole B-Chemical 0
' O 0
s O 0
role O 0
in O 0
causing O 0
TDP B-Disease 0
. O 0

CASE O 0
SUMMARY O 0
: O 0
A O 0
68 O 0
- O 0
year O 0
- O 0
old O 0
white O 0
woman O 0
with O 0
Candida O 0
glabrata O 0
isolated O 0
from O 0
a O 0
presacral O 0
abscess O 0
developed O 0
TDP B-Disease 0
eight O 0
days O 0
after O 0
commencing O 0
oral O 0
fluconazole B-Chemical 0
The O 0
patient O 0
had O 0
no O 0
other O 0
risk O 0
factors O 0
for O 0
TDP B-Disease 0
, O 0
including O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
, O 0
cardiomyopathy B-Disease 0
, O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
, O 0
and O 0
electrolyte O 0
abnormalities O 0
There O 0
was O 0
a O 0
temporal O 0
association O 0
between O 0
the O 0
initiation O 0
of O 0
fluconazole B-Chemical 0
and O 0
TDP B-Disease 0
. O 0

The O 0
TDP B-Disease 0
resolved O 0
when O 0
fluconazole B-Chemical 0
was O 0
discontinued O 0
; O 0
however O 0
, O 0
the O 0
patient O 0
continued O 0
to O 0
have O 0
premature B-Disease 0
ventricular I-Disease 0
contractions I-Disease 0
and O 0
nonsustained O 0
ventricular B-Disease 0
tachycardia I-Disease 0
( O 0
NSVT B-Disease 0
) O 0
until O 0
six O 0
days O 0
after O 0
drug O 0
cessation O 0
DISCUSSION O 0
: O 0
Use O 0
of O 0
the O 0
Naranjo O 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
use O 0
of O 0
fluconazole B-Chemical 0
and O 0
the O 0
development O 0
of O 0
TDP B-Disease 0
. O 0

The O 0
possible O 0
mechanism O 0
is O 0
depression B-Disease 0
of O 0
rapidly O 0
activating O 0
delayed O 0
rectifier O 0
potassium B-Chemical 0
currents O 0
. O 0

In O 0
our O 0
patient O 0
, O 0
there O 0
was O 0
no O 0
other O 0
etiology O 0
identified O 0
that O 0
could O 0
explain O 0
QT B-Disease 0
prolongation I-Disease 0
or O 0
TDP B-Disease 0
The O 0
complete O 0
disappearance O 0
of O 0
NSVT B-Disease 0
and O 0
premature B-Disease 0
ventricular I-Disease 0
contractions I-Disease 0
followed O 0
by O 0
normalization O 0
of O 0
QT O 0
interval O 0
after O 0
the O 0
drug O 0
was O 0
stopped O 0
strongly O 0
suggests O 0
fluconazole B-Chemical 0
as O 0
the O 0
etiology O 0
. O 0

CONCLUSIONS O 0
: O 0
Clinicians O 0
should O 0
be O 0
aware O 0
that O 0
fluconazole B-Chemical 0
, O 0
even O 0
at O 0
low O 0
doses O 0
, O 0
may O 0
cause O 0
prolongation B-Disease 0
of I-Disease 0
the I-Disease 0
QT I-Disease 0
interval I-Disease 0
, O 0
leading O 0
to O 0
TDP B-Disease 0
. O 0

Serial O 0
electrocardiographic O 0
monitoring O 0
may O 0
be O 0
considered O 0
when O 0
fluconazole B-Chemical 0
is O 0
administered O 0
in O 0
patients O 0
who O 0
are O 0
at O 0
risk O 0
for O 0
ventricular B-Disease 0
arrhythmias I-Disease 0
. O 0

Cutaneous B-Disease 0
leucocytoclastic I-Disease 0
vasculitis I-Disease 0
associated O 0
with O 0
oxacillin B-Chemical 0
. O 0

A O 0
67 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
who O 0
was O 0
treated O 0
with O 0
oxacillin B-Chemical 0
for O 0
one O 0
week O 0
because O 0
of O 0
Staphylococcus B-Disease 0
aureus I-Disease 0
bacteremia I-Disease 0
, O 0
developed O 0
renal B-Disease 0
failure I-Disease 0
and O 0
diffuse O 0
, O 0
symmetric O 0
, O 0
palpable O 0
purpuric B-Disease 0
lesions I-Disease 0
on O 0
his O 0
feet O 0
. O 0

Necrotic B-Disease 0
blisters I-Disease 0
were O 0
noted O 0
on O 0
his O 0
fingers O 0
. O 0

Skin O 0
biopsies O 0
showed O 0
findings O 0
diagnostic O 0
of O 0
leucocytoclastic B-Disease 0
vasculitis I-Disease 0
. O 0

Oxacillin B-Chemical 0
was O 0
discontinued O 0
and O 0
patient O 0
was O 0
treated O 0
with O 0
corticosteroids B-Chemical 0
. O 0

The O 0
rash B-Disease 0
disappeared O 0
after O 0
three O 0
weeks O 0
and O 0
renal O 0
function O 0
returned O 0
to O 0
normal O 0
. O 0

Leucocytoclastic B-Disease 0
vasculitis I-Disease 0
presents O 0
as O 0
palpable O 0
purpura B-Disease 0
of O 0
the O 0
lower O 0
extremities O 0
often O 0
accompanied O 0
by O 0
abdominal B-Disease 0
pain I-Disease 0
, O 0
arthralgia B-Disease 0
, O 0
and O 0
renal B-Disease 0
involvement I-Disease 0
. O 0

Etiologic O 0
factors O 0
or O 0
associated O 0
disorders O 0
include O 0
infections B-Disease 0
, O 0
medications O 0
, O 0
collagen B-Disease 0
vascular I-Disease 0
disease I-Disease 0
and O 0
neoplasia B-Disease 0
. O 0

However O 0
, O 0
in O 0
half O 0
of O 0
the O 0
cases O 0
no O 0
etiologic O 0
factor O 0
is O 0
identified O 0
. O 0

Usually O 0
it O 0
is O 0
a O 0
self O 0
- O 0
limited O 0
disorder O 0
, O 0
but O 0
corticosteroid B-Chemical 0
therapy O 0
may O 0
be O 0
needed O 0
in O 0
life O 0
- O 0
threatening O 0
cases O 0
since O 0
early O 0
treatment O 0
with O 0
corticosteroids B-Chemical 0
in O 0
severe O 0
cases O 0
can O 0
prevent O 0
complications O 0
. O 0

Oxacillin B-Chemical 0
should O 0
be O 0
included O 0
among O 0
the O 0
drugs O 0
that O 0
can O 0
cause O 0
leucocytoclastic B-Disease 0
vasculitis I-Disease 0
. O 0

The O 0
renal O 0
pathology O 0
in O 0
a O 0
case O 0
of O 0
lithium B-Chemical 0
- O 0
induced O 0
diabetes B-Disease 0
insipidus I-Disease 0
. O 0

A O 0
case O 0
of O 0
lithium B-Chemical 0
- O 0
induced O 0
diabetes B-Disease 0
insipidus I-Disease 0
is O 0
reported O 0
. O 0

At O 0
necropsy O 0
microscopy O 0
shoed O 0
unique O 0
and O 0
extensive O 0
damage O 0
to O 0
cells O 0
lining O 0
the O 0
distal O 0
nephron O 0
. O 0

It O 0
is O 0
suggested O 0
that O 0
these O 0
changes O 0
represent O 0
a O 0
specific O 0
toxic O 0
effect O 0
of O 0
lithium B-Chemical 0
, O 0
reported O 0
here O 0
for O 0
the O 0
first O 0
time O 0
in O 0
man O 0
. O 0

Cholestatic B-Disease 0
jaundice I-Disease 0
associated O 0
with O 0
the O 0
use O 0
of O 0
metformin B-Chemical 0
. O 0

We O 0
report O 0
a O 0
patient O 0
who O 0
developed O 0
cholestatic B-Disease 0
jaundice I-Disease 0
shortly O 0
after O 0
initiation O 0
of O 0
treatment O 0
with O 0
metformin B-Chemical 0
hydrochloride I-Chemical 0
. O 0

Ultrasound O 0
of O 0
the O 0
liver O 0
and O 0
abdominal O 0
CT O 0
were O 0
normal O 0
. O 0

An O 0
ERCP O 0
showed O 0
normal O 0
biliary O 0
anatomy O 0
. O 0

A O 0
percutaneous O 0
liver O 0
biopsy O 0
was O 0
obtained O 0
showing O 0
marked O 0
cholestasis B-Disease 0
, O 0
with O 0
portal O 0
edema B-Disease 0
, O 0
ductular O 0
proliferation O 0
, O 0
and O 0
acute O 0
inflammation B-Disease 0
. O 0

Metformin B-Chemical 0
hydrochloride I-Chemical 0
was O 0
discontinued O 0
, O 0
and O 0
the O 0
patient O 0
' O 0
s O 0
jaundice B-Disease 0
resolved O 0
slowly O 0
over O 0
a O 0
period O 0
of O 0
several O 0
months O 0
. O 0

Given O 0
the O 0
onset O 0
of O 0
his O 0
jaundice B-Disease 0
2 O 0
wk O 0
after O 0
the O 0
initiation O 0
of O 0
metformin B-Chemical 0
, O 0
we O 0
believe O 0
that O 0
this O 0
case O 0
represents O 0
an O 0
example O 0
of O 0
metformin B-Chemical 0
- O 0
associated O 0
hepatotoxicity B-Disease 0
, O 0
the O 0
first O 0
such O 0
case O 0
reported O 0
. O 0

Systemic O 0
toxicity B-Disease 0
and O 0
resuscitation O 0
in O 0
bupivacaine B-Chemical 0
- O 0
, O 0
levobupivacaine B-Chemical 0
- O 0
, O 0
or O 0
ropivacaine B-Chemical 0
- O 0
infused O 0
rats O 0
. O 0

We O 0
compared O 0
the O 0
systemic O 0
toxicity B-Disease 0
of O 0
bupivacaine B-Chemical 0
, O 0
levobupivacaine B-Chemical 0
, O 0
and O 0
ropivacaine B-Chemical 0
in O 0
anesthetized O 0
rats O 0
. O 0

We O 0
also O 0
compared O 0
the O 0
ability O 0
to O 0
resuscitate O 0
rats O 0
after O 0
lethal O 0
doses O 0
of O 0
these O 0
local O 0
anesthetics O 0
. O 0

Bupivacaine B-Chemical 0
, O 0
levobupivacaine B-Chemical 0
, O 0
or O 0
ropivacaine B-Chemical 0
was O 0
infused O 0
at O 0
a O 0
rate O 0
of O 0
2 O 0
mg O 0
. O 0

kg O 0
( O 0
- O 0
1 O 0
) O 0
. O 0

min O 0
( O 0
- O 0
1 O 0
) O 0
while O 0
electrocardiogram O 0
, O 0
electroencephalogram O 0
, O 0
and O 0
arterial O 0
pressure O 0
were O 0
continuously O 0
monitored O 0
. O 0

When O 0
asystole B-Disease 0
was O 0
recorded O 0
, O 0
drug O 0
infusion O 0
was O 0
stopped O 0
and O 0
a O 0
resuscitation O 0
sequence O 0
was O 0
begun O 0
. O 0

Epinephrine B-Chemical 0
0 O 0
. O 0
01 O 0
mg O 0
/ O 0
kg O 0
was O 0
administered O 0
at O 0
1 O 0
- O 0
min O 0
intervals O 0
while O 0
external O 0
cardiac O 0
compressions O 0
were O 0
applied O 0
. O 0

Resuscitation O 0
was O 0
considered O 0
successful O 0
when O 0
a O 0
systolic O 0
arterial O 0
pressure O 0
> O 0
or O 0
= O 0
100 O 0
mm O 0
Hg O 0
was O 0
achieved O 0
within O 0
5 O 0
min O 0
. O 0

The O 0
cumulative O 0
doses O 0
of O 0
levobupivacaine B-Chemical 0
and O 0
ropivacaine B-Chemical 0
that O 0
produced O 0
seizures B-Disease 0
were O 0
similar O 0
and O 0
were O 0
larger O 0
than O 0
those O 0
of O 0
bupivacaine B-Chemical 0
. O 0

The O 0
cumulative O 0
doses O 0
of O 0
levobupivacaine B-Chemical 0
that O 0
produced O 0
dysrhythmias B-Disease 0
and O 0
asystole B-Disease 0
were O 0
smaller O 0
than O 0
the O 0
corresponding O 0
doses O 0
of O 0
ropivacaine B-Chemical 0
, O 0
but O 0
they O 0
were O 0
larger O 0
than O 0
those O 0
of O 0
bupivacaine B-Chemical 0
. O 0

The O 0
number O 0
of O 0
successful O 0
resuscitations O 0
did O 0
not O 0
differ O 0
among O 0
groups O 0
. O 0

However O 0
, O 0
a O 0
smaller O 0
dose O 0
of O 0
epinephrine B-Chemical 0
was O 0
required O 0
in O 0
the O 0
Ropivacaine B-Chemical 0
group O 0
than O 0
in O 0
the O 0
other O 0
groups O 0
. O 0

We O 0
conclude O 0
that O 0
the O 0
systemic O 0
toxicity B-Disease 0
of O 0
levobupivacaine B-Chemical 0
is O 0
intermediate O 0
between O 0
that O 0
of O 0
ropivacaine B-Chemical 0
and O 0
bupivacaine B-Chemical 0
when O 0
administered O 0
at O 0
the O 0
same O 0
rate O 0
and O 0
that O 0
ropivacaine B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
arrest I-Disease 0
appears O 0
to O 0
be O 0
more O 0
susceptible O 0
to O 0
treatment O 0
than O 0
that O 0
induced O 0
by O 0
bupivacaine B-Chemical 0
or O 0
levobupivacaine B-Chemical 0
. O 0

Amphotericin B-Chemical 0
B I-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
in O 0
a O 0
patient O 0
with O 0
AIDS 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
multiple O 0
episodes O 0
of O 0
seizure B-Disease 0
activity O 0
in O 0
an O 0
AIDS B-Disease 0
patent O 0
following O 0
amphotericin B-Chemical 0
B I-Chemical 0
infusion O 0
. O 0

CASE O 0
SUMMARY O 0
: O 0
A O 0
46 O 0
- O 0
year O 0
- O 0
old O 0
African O 0
- O 0
American O 0
man O 0
experienced O 0
recurrent O 0
grand B-Disease 0
mal I-Disease 0
seizures I-Disease 0
during O 0
intravenous O 0
infusion O 0
of O 0
amphotericin B-Chemical 0
B I-Chemical 0
, O 0
then O 0
petit O 0
mal O 0
seizures B-Disease 0
as O 0
the O 0
infusion O 0
was O 0
stopped O 0
and O 0
the O 0
drug O 0
concentrations O 0
decreased O 0
with O 0
time O 0
. O 0

The O 0
patients O 0
concurrent O 0
medications O 0
included O 0
didanosine B-Chemical 0
, O 0
hydroxyzine B-Chemical 0
, O 0
promethazine B-Chemical 0
, O 0
hydrocortisone B-Chemical 0
, O 0
and O 0
prochlorperazine B-Chemical 0
. O 0

Despite O 0
administration O 0
of O 0
phenytoin B-Chemical 0
and O 0
lorazepam B-Chemical 0
, O 0
the O 0
seizures B-Disease 0
persisted O 0
and O 0
occurred O 0
only O 0
during O 0
amphotercin B-Chemical 0
B I-Chemical 0
administration O 0
. O 0

DISCUSSION O 0
: O 0
AIDS B-Disease 0
and O 0
cryptococcal B-Disease 0
meningitis I-Disease 0
, O 0
both O 0
of O 0
which O 0
the O 0
patient O 0
had O 0
, O 0
can O 0
potentially O 0
cause O 0
seizures B-Disease 0
. O 0

The O 0
patient O 0
had O 0
a O 0
history O 0
of O 0
alcohol B-Disease 0
abuse I-Disease 0
; O 0
alcohol B-Chemical 0
intake O 0
as O 0
well O 0
as O 0
withdrawal O 0
can O 0
also O 0
cause O 0
seizures B-Disease 0
. O 0

Didanosine B-Chemical 0
also O 0
has O 0
a O 0
potential O 0
for O 0
inducing O 0
seizures B-Disease 0
. O 0

However O 0
, O 0
these O 0
other O 0
potential O 0
causes O 0
of O 0
seizure B-Disease 0
were O 0
ruled O 0
out O 0
. O 0

The O 0
time O 0
course O 0
of O 0
events O 0
suggested O 0
that O 0
amphotericin B-Chemical 0
B I-Chemical 0
was O 0
the O 0
cause O 0
of O 0
the O 0
seizures B-Disease 0
in O 0
this O 0
AIDS B-Disease 0
patient O 0
. O 0

CONCLUSIONS O 0
: O 0
Amphotericin B-Chemical 0
B I-Chemical 0
seems O 0
to O 0
be O 0
the O 0
probable O 0
cause O 0
of O 0
the O 0
seizures B-Disease 0
. O 0

To O 0
date O 0
, O 0
only O 0
three O 0
cases O 0
of O 0
seizures B-Disease 0
associated O 0
with O 0
amphotericin B-Chemical 0
B I-Chemical 0
have O 0
been O 0
reported O 0
in O 0
the O 0
literature O 0
, O 0
but O 0
healthcare O 0
providers O 0
should O 0
be O 0
aware O 0
of O 0
the O 0
potential O 0
for O 0
this O 0
rare O 0
adverse O 0
effect O 0
. O 0

Sirolimus B-Chemical 0
and O 0
mycophenolate B-Chemical 0
mofetil I-Chemical 0
for O 0
calcineurin O 0
- O 0
free O 0
immunosuppression O 0
in O 0
renal O 0
transplant O 0
recipients O 0
. O 0

Calcineurin O 0
inhibitors O 0
, O 0
such O 0
as O 0
cyclosporine B-Chemical 0
and O 0
tacrolimus B-Chemical 0
, O 0
have O 0
been O 0
available O 0
for O 0
almost O 0
20 O 0
years O 0
. O 0

Although O 0
these O 0
drugs O 0
are O 0
highly O 0
effective O 0
and O 0
represent O 0
the O 0
mainstay O 0
of O 0
transplant O 0
immunosuppression O 0
, O 0
they O 0
are O 0
associated O 0
with O 0
acute O 0
and O 0
chronic O 0
nephrotoxicity B-Disease 0
. O 0

Acute O 0
nephrotoxicity B-Disease 0
, O 0
which O 0
occurs O 0
in O 0
the O 0
early O 0
period O 0
after O 0
transplantation O 0
, O 0
leads O 0
to O 0
a O 0
higher O 0
rate O 0
of O 0
dialysis O 0
, O 0
and O 0
chronic O 0
nephrotoxicity B-Disease 0
may O 0
eventually O 0
result O 0
in O 0
graft O 0
loss O 0
. O 0

Acute O 0
and O 0
chronic O 0
nephrotoxicity B-Disease 0
is O 0
becoming O 0
more O 0
common O 0
as O 0
the O 0
use O 0
of O 0
marginal O 0
kidneys O 0
for O 0
transplantation O 0
increases O 0
. O 0

Two O 0
recently O 0
available O 0
immunosuppressive O 0
agents O 0
, O 0
mycophenolate B-Chemical 0
mofetil I-Chemical 0
and O 0
sirolimus B-Chemical 0
( O 0
rapamycin B-Chemical 0
) O 0
, O 0
have O 0
no O 0
nephrotoxicity B-Disease 0
. O 0

The O 0
use O 0
of O 0
these O 0
drugs O 0
in O 0
combination O 0
with O 0
other O 0
agents O 0
has O 0
led O 0
to O 0
the O 0
development O 0
of O 0
new O 0
paradigms O 0
of O 0
immunosuppressive O 0
therapy O 0
. O 0

This O 0
paper O 0
reviews O 0
the O 0
results O 0
of O 0
clinical O 0
trials O 0
that O 0
have O 0
investigated O 0
these O 0
new O 0
approaches O 0
to O 0
immunosuppression O 0
in O 0
renal O 0
transplant O 0
recipients O 0
. O 0

Tolerability O 0
of O 0
nimesulide B-Chemical 0
and O 0
paracetamol B-Chemical 0
in O 0
patients O 0
with O 0
NSAID B-Chemical 0
- O 0
induced O 0
urticaria B-Disease 0
/ O 0
angioedema B-Disease 0
. O 0

Previous O 0
studies O 0
evaluated O 0
the O 0
tolerance O 0
of O 0
nimesulide B-Chemical 0
and O 0
paracetamol B-Chemical 0
in O 0
subjects O 0
with O 0
cutaneous O 0
, O 0
respiratory O 0
and O 0
anaphylactoid O 0
reactions O 0
induced O 0
by O 0
nonsteroidal B-Chemical 0
anti I-Chemical 0
- I-Chemical 0
inflammatory I-Chemical 0
drugs I-Chemical 0
( O 0
NSAIDs B-Chemical 0
) O 0
. O 0

In O 0
this O 0
study O 0
we O 0
investigated O 0
tolerability O 0
and O 0
reliability O 0
of O 0
nimesulide B-Chemical 0
and O 0
paracetamol B-Chemical 0
in O 0
a O 0
very O 0
large O 0
number O 0
of O 0
patients O 0
with O 0
an O 0
exclusive O 0
well O 0
- O 0
documented O 0
history O 0
of O 0
NSAID B-Chemical 0
- O 0
induced O 0
urticaria B-Disease 0
/ O 0
angioedema B-Disease 0
. O 0

Furthermore O 0
, O 0
we O 0
evaluated O 0
whether O 0
some O 0
factors O 0
have O 0
the O 0
potential O 0
to O 0
increase O 0
the O 0
risk O 0
of O 0
reaction O 0
to O 0
paracetamol B-Chemical 0
and O 0
nimesulide B-Chemical 0
. O 0

A O 0
single O 0
- O 0
placebo O 0
- O 0
controlled O 0
oral O 0
challenge O 0
procedure O 0
with O 0
nimesulide B-Chemical 0
or O 0
paracetamol B-Chemical 0
was O 0
applied O 0
to O 0
829 O 0
patients O 0
with O 0
a O 0
history O 0
of O 0
NSAID B-Chemical 0
- O 0
induced O 0
urticaria B-Disease 0
/ O 0
angioedema B-Disease 0
. O 0

A O 0
total O 0
of O 0
75 O 0
/ O 0
829 O 0
( O 0
9 O 0
. O 0
4 O 0
% O 0
) O 0
patients O 0
experienced O 0
reactions O 0
to O 0
nimesulide B-Chemical 0
or O 0
paracetamol B-Chemical 0
. O 0

Of O 0
the O 0
715 O 0
patients O 0
tested O 0
with O 0
nimesulide B-Chemical 0
62 O 0
( O 0
8 O 0
. O 0
6 O 0
% O 0
) O 0
showed O 0
a O 0
positive O 0
test O 0
, O 0
while O 0
of O 0
114 O 0
subjects O 0
submitted O 0
to O 0
the O 0
challenge O 0
with O 0
paracetamol B-Chemical 0
, O 0
13 O 0
( O 0
9 O 0
. O 0
6 O 0
% O 0
) O 0
did O 0
not O 0
tolerate O 0
this O 0
drug O 0
. O 0

Furthermore O 0
, O 0
18 O 0
. O 0
28 O 0
% O 0
of O 0
patients O 0
with O 0
a O 0
history O 0
of O 0
chronic O 0
urticaria B-Disease 0
and O 0
11 O 0
. O 0
8 O 0
% O 0
of O 0
subjects O 0
with O 0
an O 0
history O 0
of O 0
NSAID B-Chemical 0
- O 0
induced O 0
urticaria B-Disease 0
/ O 0
angioedema B-Disease 0
or O 0
angioedema B-Disease 0
alone O 0
( O 0
with O 0
or O 0
without O 0
chronic O 0
urticaria B-Disease 0
) O 0
resulted O 0
to O 0
be O 0
intolerant O 0
to O 0
alternative O 0
drugs O 0
. O 0

Taken O 0
together O 0
, O 0
our O 0
results O 0
confirm O 0
the O 0
good O 0
tolerability O 0
of O 0
nimesulide B-Chemical 0
and O 0
paracetamol B-Chemical 0
in O 0
patients O 0
who O 0
experienced O 0
urticaria B-Disease 0
/ O 0
angioedema B-Disease 0
caused O 0
by O 0
NSAIDs B-Chemical 0
. O 0

However O 0
, O 0
the O 0
risk O 0
of O 0
reaction O 0
to O 0
these O 0
alternative O 0
study O 0
drugs O 0
is O 0
statistically O 0
increased O 0
by O 0
a O 0
history O 0
of O 0
chronic O 0
urticaria B-Disease 0
and O 0
, O 0
above O 0
all O 0
, O 0
by O 0
a O 0
history O 0
of O 0
NSAID B-Chemical 0
- O 0
induced O 0
angioedema B-Disease 0
. O 0

Comparison O 0
of O 0
aqueous O 0
and O 0
gellan O 0
ophthalmic O 0
timolol B-Chemical 0
with O 0
placebo O 0
on O 0
the O 0
24 O 0
- O 0
hour O 0
heart O 0
rate O 0
response O 0
in O 0
patients O 0
on O 0
treatment O 0
for O 0
glaucoma B-Disease 0
. O 0

PURPOSE O 0
: O 0
Topical O 0
beta O 0
- O 0
blocker O 0
treatment O 0
is O 0
routine O 0
therapy O 0
in O 0
the O 0
management O 0
of O 0
patients O 0
with O 0
glaucoma B-Disease 0
. O 0

Therapy O 0
results O 0
in O 0
systemic O 0
absorption O 0
, O 0
however O 0
, O 0
the O 0
degree O 0
of O 0
reduction O 0
of O 0
resting O 0
and O 0
peak O 0
heart O 0
rate O 0
has O 0
not O 0
been O 0
quantified O 0
. O 0

DESIGN O 0
: O 0
This O 0
trial O 0
evaluated O 0
the O 0
effect O 0
of O 0
placebo O 0
, O 0
0 O 0
. O 0
5 O 0
% O 0
aqueous O 0
timolol B-Chemical 0
( O 0
timolol B-Chemical 0
solution O 0
) O 0
and O 0
a O 0
0 O 0
. O 0
5 O 0
% O 0
timolol B-Chemical 0
suspension O 0
that O 0
forms O 0
a O 0
gel O 0
on O 0
application O 0
to O 0
the O 0
conjunctiva O 0
( O 0
timolol B-Chemical 0
gellan O 0
) O 0
on O 0
the O 0
24 O 0
- O 0
hour O 0
heart O 0
rate O 0
in O 0
patients O 0
currently O 0
being O 0
treated O 0
for O 0
glaucoma B-Disease 0
to O 0
quantify O 0
the O 0
reduction O 0
in O 0
mean O 0
heart O 0
rate O 0
. O 0

METHODS O 0
: O 0
Forty O 0
- O 0
three O 0
Caucasian O 0
patients O 0
with O 0
primary O 0
open B-Disease 0
- I-Disease 0
angle I-Disease 0
glaucoma I-Disease 0
or O 0
ocular B-Disease 0
hypertension I-Disease 0
with O 0
a O 0
mean O 0
( O 0
+ O 0
/ O 0
- O 0
SD O 0
) O 0
age O 0
of O 0
63 O 0
( O 0
+ O 0
/ O 0
- O 0
8 O 0
) O 0
years O 0
were O 0
randomized O 0
and O 0
crossed O 0
over O 0
in O 0
a O 0
double O 0
- O 0
masked O 0
manner O 0
to O 0
14 O 0
days O 0
of O 0
treatment O 0
with O 0
placebo O 0
( O 0
morning O 0
and O 0
evening O 0
in O 0
both O 0
eyes O 0
) O 0
, O 0
timolol B-Chemical 0
solution O 0
( O 0
morning O 0
and O 0
evening O 0
in O 0
both O 0
eyes O 0
) O 0
, O 0
or O 0
timolol B-Chemical 0
gellan O 0
( O 0
morning O 0
in O 0
both O 0
eyes O 0
with O 0
placebo O 0
in O 0
the O 0
evening O 0
) O 0
. O 0

On O 0
the O 0
13th O 0
day O 0
of O 0
each O 0
period O 0
, O 0
heart O 0
rate O 0
was O 0
recorded O 0
continuously O 0
during O 0
a O 0
typical O 0
, O 0
ambulant O 0
24 O 0
- O 0
hour O 0
period O 0
. O 0

RESULTS O 0
: O 0
Both O 0
timolol B-Chemical 0
solution O 0
and O 0
timolol B-Chemical 0
gellan O 0
reduced O 0
the O 0
mean O 0
24 O 0
- O 0
hour O 0
heart O 0
rate O 0
compared O 0
with O 0
placebo O 0
( O 0
P O 0
< O 0
or O 0
= O 0
. O 0
001 O 0
) O 0
, O 0
and O 0
this O 0
reduction O 0
was O 0
most O 0
pronounced O 0
during O 0
the O 0
daytime O 0
( O 0
- O 0
7 O 0
. O 0
5 O 0
% O 0
change O 0
in O 0
mean O 0
heart O 0
rate O 0
, O 0
- O 0
5 O 0
. O 0
7 O 0
beats O 0
/ O 0
min O 0
) O 0
. O 0

Timolol B-Chemical 0
gellan O 0
showed O 0
a O 0
numerically O 0
but O 0
not O 0
significantly O 0
smaller O 0
reduction O 0
in O 0
24 O 0
- O 0
hour O 0
heart O 0
rate O 0
, O 0
compared O 0
with O 0
timolol B-Chemical 0
solution O 0
. O 0

During O 0
the O 0
night O 0
, O 0
the O 0
mean O 0
12 O 0
- O 0
hour O 0
heart O 0
rate O 0
on O 0
placebo O 0
and O 0
timolol B-Chemical 0
gellan O 0
were O 0
both O 0
significantly O 0
less O 0
than O 0
on O 0
timolol B-Chemical 0
solution O 0
; O 0
the O 0
difference O 0
between O 0
solution O 0
and O 0
gellan O 0
treatments O 0
was O 0
statistically O 0
significant O 0
( O 0
P O 0
= O 0
. O 0
01 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Both O 0
timolol B-Chemical 0
solution O 0
and O 0
timolol B-Chemical 0
gellan O 0
decrease O 0
the O 0
mean O 0
24 O 0
- O 0
hour O 0
heart O 0
rate O 0
compared O 0
with O 0
placebo O 0
. O 0

This O 0
response O 0
was O 0
most O 0
pronounced O 0
during O 0
the O 0
active O 0
daytime O 0
period O 0
. O 0

These O 0
data O 0
quantify O 0
the O 0
modest O 0
bradycardia B-Disease 0
associated O 0
with O 0
ophthalmic O 0
beta O 0
- O 0
blocker O 0
therapy O 0
in O 0
a O 0
typical O 0
patient O 0
population O 0
on O 0
therapy O 0
for O 0
glaucoma B-Disease 0
. O 0

Although O 0
exercise O 0
performance O 0
was O 0
not O 0
assessed O 0
in O 0
this O 0
trial O 0
, O 0
reductions O 0
of O 0
this O 0
magnitude O 0
should O 0
not O 0
have O 0
substantial O 0
clinical O 0
consequences O 0
. O 0

Management O 0
strategies O 0
for O 0
ribavirin B-Chemical 0
- O 0
induced O 0
hemolytic B-Disease 0
anemia I-Disease 0
in O 0
the O 0
treatment O 0
of O 0
hepatitis B-Disease 0
C I-Disease 0
: O 0
clinical O 0
and O 0
economic O 0
implications O 0
. O 0

OBJECTIVES O 0
: O 0
Recently O 0
published O 0
studies O 0
have O 0
demonstrated O 0
increased O 0
efficacy O 0
and O 0
cost O 0
- O 0
effectiveness O 0
of O 0
combination O 0
therapy O 0
with O 0
interferon O 0
and O 0
alpha O 0
- O 0
2b O 0
/ O 0
ribavirin B-Chemical 0
compared O 0
with O 0
interferon B-Chemical 0
- I-Chemical 0
alpha I-Chemical 0
monotherapy O 0
in O 0
the O 0
treatment O 0
of O 0
chronic B-Disease 0
hepatitis I-Disease 0
C I-Disease 0
( O 0
CHC B-Disease 0
) O 0
. O 0

Combination O 0
therapy O 0
is O 0
associated O 0
with O 0
a O 0
clinically O 0
important O 0
adverse O 0
effect O 0
: O 0
ribavirin B-Chemical 0
- O 0
induced O 0
hemolytic B-Disease 0
anemia I-Disease 0
( O 0
RIHA B-Disease 0
) 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
evaluate O 0
the O 0
direct O 0
health O 0
- O 0
care O 0
costs O 0
and O 0
management O 0
of O 0
RIHA B-Disease 0
during O 0
treatment O 0
of O 0
CHC B-Disease 0
in O 0
a O 0
clinical O 0
trial O 0
setting O 0
. O 0

METHODS O 0
: O 0
A O 0
systematic O 0
literature O 0
review O 0
was O 0
conducted O 0
to O 0
synthesize O 0
information O 0
on O 0
the O 0
incidence O 0
and O 0
management O 0
of O 0
RIHA B-Disease 0
. O 0

Decision O 0
- O 0
analytic O 0
techniques O 0
were O 0
used O 0
to O 0
estimate O 0
the O 0
cost O 0
of O 0
treating O 0
RIHA B-Disease 0
. O 0

Uncertainty O 0
was O 0
evaluated O 0
using O 0
sensitivity O 0
analyses O 0
. O 0

RESULTS O 0
: O 0
RIHA B-Disease 0
, O 0
defined O 0
as O 0
a O 0
reduction O 0
in O 0
hemoglobin O 0
to O 0
less O 0
than O 0
100 O 0
g O 0
/ O 0
L O 0
, O 0
occurs O 0
in O 0
approximately O 0
7 O 0
% O 0
to O 0
9 O 0
% O 0
of O 0
patients O 0
treated O 0
with O 0
combination O 0
therapy O 0
. O 0

The O 0
standard O 0
of O 0
care O 0
for O 0
management O 0
of O 0
RIHA B-Disease 0
is O 0
reduction O 0
or O 0
discontinuation O 0
of O 0
the O 0
ribavirin B-Chemical 0
dosage O 0
. O 0

We O 0
estimated O 0
the O 0
direct O 0
cost O 0
of O 0
treating O 0
clinically O 0
significant O 0
RIHA B-Disease 0
to O 0
be O 0
170 O 0
per O 0
patient O 0
receiving O 0
combination O 0
therapy O 0
per O 0
48 O 0
- O 0
week O 0
treatment O 0
course O 0
( O 0
range O 0
68 O 0
- O 0
692 O 0
) O 0
. O 0

The O 0
results O 0
of O 0
the O 0
one O 0
- O 0
way O 0
sensitivity O 0
analyses O 0
ranged O 0
from O 0
57 O 0
to O 0
317 O 0
. O 0

In O 0
comparison O 0
, O 0
the O 0
cost O 0
of O 0
48 O 0
weeks O 0
of O 0
combination O 0
therapy O 0
is O 0
16 O 0
, O 0
459 O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
direct O 0
cost O 0
of O 0
treating O 0
clinically O 0
significant O 0
RIHA B-Disease 0
is O 0
1 O 0
% O 0
( O 0
170 O 0
/ O 0
16 O 0
, O 0
459 O 0
) O 0
of O 0
drug O 0
treatment O 0
costs O 0
. O 0

Questions O 0
remain O 0
about O 0
the O 0
optimal O 0
dose O 0
of O 0
ribavirin B-Chemical 0
and O 0
the O 0
incidence O 0
of O 0
RIHA B-Disease 0
in O 0
a O 0
real O 0
- O 0
world O 0
population O 0
. O 0

Despite O 0
these O 0
uncertainties O 0
, O 0
this O 0
initial O 0
evaluation O 0
of O 0
the O 0
direct O 0
cost O 0
of O 0
treating O 0
RIHA B-Disease 0
provides O 0
an O 0
estimate O 0
of O 0
the O 0
cost O 0
and O 0
management O 0
implications O 0
of O 0
this O 0
clinically O 0
important O 0
adverse O 0
effect O 0
. O 0

Preliminary O 0
efficacy O 0
assessment O 0
of O 0
intrathecal O 0
injection O 0
of O 0
an O 0
American O 0
formulation O 0
of O 0
adenosine B-Chemical 0
in O 0
humans O 0
. O 0

BACKGROUND O 0
: O 0
Preclinical O 0
studies O 0
of O 0
intrathecal O 0
adenosine B-Chemical 0
suggest O 0
it O 0
may O 0
be O 0
effective O 0
in O 0
the O 0
treatment O 0
of O 0
acute B-Disease 0
and I-Disease 0
chronic I-Disease 0
pain I-Disease 0
in O 0
humans O 0
, O 0
and O 0
preliminary O 0
studies O 0
in O 0
volunteers O 0
and O 0
patients O 0
with O 0
a O 0
Swedish O 0
formulation O 0
of O 0
adenosine B-Chemical 0
suggests O 0
it O 0
may O 0
be O 0
effective O 0
in O 0
hypersensitivity B-Disease 0
states O 0
but O 0
not O 0
with O 0
acute O 0
noxious O 0
stimulation 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
screen O 0
for O 0
efficacy O 0
of O 0
a O 0
different O 0
formulation O 0
of O 0
adenosine B-Chemical 0
marketed O 0
in O 0
the O 0
US O 0
, O 0
using O 0
both O 0
acute O 0
noxious O 0
stimulation O 0
and O 0
capsaicin B-Chemical 0
- O 0
evoked O 0
mechanical O 0
hypersensitivity B-Disease 0
. O 0

METHODS O 0
: O 0
Following O 0
Food O 0
and O 0
Drug O 0
Administration O 0
and O 0
institutional O 0
review O 0
board O 0
approval O 0
and O 0
written O 0
informed O 0
consent O 0
, O 0
65 O 0
volunteers O 0
were O 0
studied O 0
in O 0
two O 0
trials O 0
: O 0
an O 0
open O 0
- O 0
label O 0
, O 0
dose O 0
- O 0
escalating O 0
trial O 0
with O 0
intrathecal O 0
adenosine B-Chemical 0
doses O 0
of O 0
0 O 0
. O 0
25 O 0
- O 0
2 O 0
. O 0
0 O 0
mg O 0
and O 0
a O 0
double O 0
- O 0
blind O 0
, O 0
placebo O 0
- O 0
controlled O 0
trial O 0
of O 0
adenosine B-Chemical 0
, O 0
2 O 0
mg O 0
. O 0

Cerebrospinal O 0
fluid O 0
was O 0
obtained O 0
for O 0
pharmacokinetic O 0
analysis O 0
, O 0
and O 0
pain B-Disease 0
ratings O 0
in O 0
response O 0
to O 0
acute O 0
heat O 0
stimuli O 0
and O 0
areas O 0
of O 0
mechanical B-Disease 0
hyperalgesia I-Disease 0
and O 0
allodynia B-Disease 0
after O 0
intradermal O 0
capsaicin B-Chemical 0
injection O 0
were O 0
determined O 0
. O 0

RESULTS O 0
: O 0
Adenosine B-Chemical 0
produced O 0
no O 0
effect O 0
on O 0
pain B-Disease 0
report O 0
to O 0
acute O 0
noxious O 0
thermal O 0
or O 0
chemical O 0
stimulation O 0
but O 0
reduced O 0
mechanical B-Disease 0
hyperalgesia I-Disease 0
and O 0
allodynia B-Disease 0
from O 0
intradermal O 0
capsaicin B-Chemical 0
injection O 0
for O 0
at O 0
least O 0
24 O 0
h O 0
. O 0

In O 0
contrast O 0
, O 0
residence O 0
time O 0
of O 0
adenosine B-Chemical 0
in O 0
cerebrospinal O 0
fluid O 0
was O 0
short O 0
( O 0
< O 0
4 O 0
h O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
These O 0
results O 0
show O 0
selective O 0
inhibition O 0
by O 0
intrathecal O 0
adenosine B-Chemical 0
of O 0
hypersensitivity B-Disease 0
, O 0
presumed O 0
to O 0
reflect O 0
central O 0
sensitization O 0
in O 0
humans O 0
after O 0
peripheral O 0
capsaicin B-Chemical 0
injection O 0
. O 0

The O 0
long O 0
- O 0
lasting O 0
effect O 0
is O 0
consistent O 0
with O 0
that O 0
observed O 0
in O 0
preliminary O 0
reports O 0
of O 0
patients O 0
with O 0
chronic O 0
neuropathic B-Disease 0
pain I-Disease 0
and O 0
is O 0
not O 0
due O 0
to O 0
prolonged O 0
residence O 0
of O 0
adenosine B-Chemical 0
in O 0
cerebrospinal O 0
fluid O 0
. O 0

Delayed O 0
- O 0
onset O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
. O 0

BACKGROUND O 0
: O 0
Heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
presents O 0
5 O 0
to O 0
12 O 0
days O 0
after O 0
heparin B-Chemical 0
exposure O 0
, O 0
with O 0
or O 0
without O 0
arterial B-Disease 0
or I-Disease 0
venous I-Disease 0
thromboemboli I-Disease 0
. O 0

Delayed O 0
recognition O 0
and O 0
treatment O 0
of O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
contribute O 0
to O 0
poor O 0
patient O 0
outcomes O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
describe O 0
and O 0
increase O 0
awareness O 0
of O 0
a O 0
clinical O 0
scenario O 0
in O 0
which O 0
the O 0
onset O 0
or O 0
manifestations O 0
of O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
are O 0
delayed O 0
. O 0

DESIGN O 0
: O 0
Retrospective O 0
case O 0
series O 0
. O 0

SETTING O 0
: O 0
Three O 0
large O 0
urban O 0
hospitals O 0
( O 0
with O 0
active O 0
cardiovascular O 0
surgery O 0
programs O 0
) O 0
. O 0

PATIENTS O 0
: O 0
14 O 0
patients O 0
seen O 0
over O 0
a O 0
3 O 0
- O 0
year O 0
period O 0
in O 0
whom O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
became O 0
apparent O 0
on O 0
delayed O 0
presentation O 0
with O 0
thromboembolic B-Disease 0
complications O 0
. O 0

MEASUREMENTS O 0
: O 0
Platelet O 0
counts O 0
, O 0
onset O 0
of O 0
objectively O 0
determined O 0
thromboembolism B-Disease 0
, O 0
results O 0
of O 0
heparin B-Chemical 0
- O 0
induced O 0
platelet O 0
factor O 0
4 O 0
antibody O 0
tests O 0
, O 0
and O 0
outcomes O 0
. O 0

RESULTS O 0
: O 0
Patients O 0
went O 0
home O 0
after O 0
hospitalizations O 0
that O 0
had O 0
included O 0
heparin B-Chemical 0
exposure O 0
- O 0
- O 0
in O 0
most O 0
cases O 0
, O 0
with O 0
no O 0
thrombocytopenia B-Disease 0
recognized O 0
- O 0
- O 0
only O 0
to O 0
return O 0
to O 0
the O 0
hospital O 0
( O 0
median O 0
, O 0
day O 0
14 O 0
) O 0
with O 0
thromboembolic B-Disease 0
complications O 0
. O 0

Thromboemboli B-Disease 0
were O 0
venous O 0
( O 0
12 O 0
patients O 0
, O 0
7 O 0
with O 0
pulmonary B-Disease 0
emboli I-Disease 0
) O 0
or O 0
arterial O 0
( O 0
4 O 0
patients O 0
) O 0
or O 0
both O 0
. O 0

Platelet O 0
counts O 0
were O 0
mildly O 0
decreased O 0
in O 0
all O 0
but O 0
2 O 0
patients O 0
on O 0
second O 0
presentation O 0
. O 0

On O 0
readmission O 0
, O 0
11 O 0
patients O 0
received O 0
therapeutic O 0
heparin B-Chemical 0
, O 0
which O 0
worsened O 0
the O 0
patients O 0
' O 0
clinical O 0
condition O 0
and O 0
, O 0
in O 0
all O 0
11 O 0
cases O 0
, O 0
decreased O 0
the O 0
platelet O 0
count O 0
( O 0
mean O 0
at O 0
readmission O 0
, O 0
143 O 0
x O 0
10 O 0
( O 0
9 O 0
) O 0
cells O 0
/ O 0
L O 0
; O 0
mean O 0
nadir O 0
after O 0
heparin B-Chemical 0
re O 0
- O 0
exposure O 0
, O 0
39 O 0
x O 0
10 O 0
( O 0
9 O 0
) O 0
cells O 0
/ O 0
L O 0
) O 0
. O 0

Results O 0
of O 0
serologic O 0
tests O 0
for O 0
heparin B-Chemical 0
- O 0
induced O 0
antibodies O 0
were O 0
positive O 0
in O 0
all O 0
patients O 0
. O 0

Subsequent O 0
treatments O 0
included O 0
alternative O 0
anticoagulants O 0
( O 0
11 O 0
patients O 0
) O 0
, O 0
thrombolytic O 0
drugs O 0
( O 0
3 O 0
patients O 0
) O 0
, O 0
inferior O 0
vena O 0
cava O 0
filters O 0
( O 0
3 O 0
patients O 0
) O 0
and O 0
, O 0
eventually O 0
, O 0
warfarin B-Chemical 0
( O 0
11 O 0
patients O 0
) O 0
. O 0

Three O 0
patients O 0
died O 0
. O 0

CONCLUSIONS O 0
: O 0
Delayed O 0
- O 0
onset O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
is O 0
increasingly O 0
being O 0
recognized O 0
. O 0

To O 0
avoid O 0
disastrous O 0
outcomes O 0
, O 0
physicians O 0
must O 0
consider O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
whenever O 0
a O 0
recently O 0
hospitalized O 0
patient O 0
returns O 0
with O 0
thromboembolism B-Disease 0
; O 0
therapy O 0
with O 0
alternative O 0
anticoagulants O 0
, O 0
not O 0
heparin B-Chemical 0
, O 0
should O 0
be O 0
initiated O 0
. O 0

Treatment O 0
of O 0
risperidone B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
with O 0
a O 0
dopamine B-Chemical 0
agonist O 0
in O 0
children O 0
. O 0

BACKGROUND O 0
: O 0
Risperidone B-Chemical 0
, O 0
a O 0
potent O 0
antagonist O 0
of O 0
both O 0
serotonergic O 0
( O 0
5HT2A O 0
) O 0
and O 0
dopaminergic O 0
D2 O 0
receptors O 0
is O 0
associated O 0
with O 0
hyperprolactinemia B-Disease 0
in O 0
adults O 0
and O 0
children O 0
. O 0

Chronically O 0
elevated O 0
prolactin O 0
levels O 0
in O 0
children O 0
with O 0
prolactinomas B-Disease 0
may O 0
be O 0
associated O 0
with O 0
arrested O 0
growth O 0
and O 0
development O 0
resulting O 0
in O 0
either O 0
delayed B-Disease 0
puberty I-Disease 0
or O 0
short O 0
stature O 0
. O 0

These O 0
possibilities O 0
stress O 0
the O 0
importance O 0
of O 0
developing O 0
a O 0
safe O 0
and O 0
effective O 0
approach O 0
to O 0
drug O 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
in O 0
youth O 0
. O 0

We O 0
report O 0
the O 0
successful O 0
treatment O 0
of O 0
risperidone B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
with O 0
cabergoline B-Chemical 0
in O 0
youth O 0
. O 0

METHODS O 0
: O 0
We O 0
undertook O 0
a O 0
retrospective O 0
case O 0
review O 0
of O 0
four O 0
children O 0
with O 0
risperidone B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
treated O 0
with O 0
cabergoline B-Chemical 0
. O 0

RESULTS O 0
: O 0
Four O 0
males O 0
( O 0
age O 0
6 O 0
- O 0
11 O 0
years O 0
) O 0
with 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
) O 0
bipolar B-Disease 0
disorder I-Disease 0
or O 0
psychoses B-Disease 0
, O 0
with O 0
risperidone B-Chemical 0
- O 0
induced O 0
elevations O 0
in O 0
serum O 0
prolactin O 0
levels O 0
( O 0
57 O 0
. O 0
5 O 0
- O 0
129 O 0
ng O 0
/ O 0
mL O 0
, O 0
normal O 0
5 O 0
- O 0
15 O 0
ng O 0
/ O 0
mL O 0
) O 0
, O 0
were O 0
treated O 0
with O 0
cabergoline B-Chemical 0
( O 0
mean O 0
dose O 0
2 O 0
. O 0
13 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
09 O 0
mg O 0
/ O 0
week O 0
) O 0
. O 0

When O 0
serum O 0
prolactin O 0
levels O 0
normalized O 0
in O 0
all O 0
four O 0
subjects O 0
( O 0
mean O 0
11 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
10 O 0
. O 0
9 O 0
ng O 0
/ O 0
mL O 0
) O 0
, O 0
the O 0
cabergoline B-Chemical 0
dose O 0
was O 0
reduced O 0
to O 0
1 O 0
mg O 0
/ O 0
week O 0
in O 0
three O 0
of O 0
four O 0
subjects O 0
. O 0

The O 0
mean O 0
duration O 0
of O 0
therapy O 0
with O 0
cabergoline B-Chemical 0
was O 0
523 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
129 O 0
. O 0
7 O 0
days O 0
, O 0
and O 0
the O 0
mean O 0
duration O 0
of O 0
therapy O 0
with O 0
risperidone B-Chemical 0
was O 0
788 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
162 O 0
. O 0
5 O 0
days O 0
. O 0

Cabergoline B-Chemical 0
was O 0
well O 0
tolerated O 0
without O 0
adverse O 0
effects O 0
. O 0

CONCLUSIONS O 0
: O 0
Cabergoline B-Chemical 0
may O 0
be O 0
useful O 0
for O 0
the O 0
treatment O 0
of O 0
risperidone B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
in O 0
youth O 0
; O 0
however O 0
, O 0
further O 0
research O 0
is O 0
needed O 0
. O 0

Acute O 0
cholestatic B-Disease 0
hepatitis I-Disease 0
after O 0
exposure O 0
to O 0
isoflurane 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
acute O 0
cholestatic B-Disease 0
hepatitis I-Disease 0
following O 0
exposure O 0
to O 0
the O 0
inhalational O 0
anesthetic O 0
isoflurane B-Chemical 0
. O 0

CASE O 0
SUMMARY O 0
: O 0
A O 0
70 O 0
- O 0
year O 0
- O 0
old O 0
healthy O 0
woman O 0
from O 0
Iraq O 0
developed O 0
acute O 0
cholestatic B-Disease 0
hepatitis I-Disease 0
3 O 0
weeks O 0
following O 0
repair O 0
of O 0
the O 0
right O 0
rotator O 0
cuff O 0
under O 0
general O 0
anesthesia O 0
. O 0

There O 0
was O 0
no O 0
evidence O 0
for O 0
viral O 0
, O 0
autoimmune O 0
, O 0
or O 0
metabolic O 0
causes O 0
of O 0
hepatitis B-Disease 0
. O 0

No O 0
other O 0
medications O 0
were O 0
involved O 0
except O 0
for O 0
dipyrone B-Chemical 0
for O 0
analgesia B-Disease 0
. O 0

The O 0
alanine B-Chemical 0
aminotransferase O 0
was O 0
elevated O 0
to O 0
a O 0
peak O 0
concentration O 0
of O 0
1533 O 0
U O 0
/ O 0
L O 0
and O 0
the O 0
serum O 0
bilirubin B-Chemical 0
reached O 0
a O 0
peak O 0
of O 0
17 O 0
. O 0
0 O 0
mg O 0
/ O 0
dL O 0
. O 0

There O 0
was O 0
slow O 0
improvement O 0
over O 0
4 O 0
months O 0
. O 0

Accidental O 0
reexposure O 0
by O 0
the O 0
patient O 0
to O 0
dipyrone B-Chemical 0
was O 0
uneventful O 0
. O 0

DISCUSSION O 0
: O 0
The O 0
clinical O 0
and O 0
histologic O 0
picture O 0
of O 0
this O 0
case O 0
resembles O 0
halothane B-Disease 0
hepatitis I-Disease 0
, O 0
which O 0
has O 0
a O 0
significant O 0
mortality O 0
rate O 0
. O 0

CONCLUSIONS O 0
: O 0
Isoflurane B-Chemical 0
, O 0
a O 0
common O 0
anesthetic O 0
agent O 0
, O 0
can O 0
cause O 0
severe O 0
cholestatic B-Disease 0
hepatitis I-Disease 0
. O 0

Torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
induced O 0
by O 0
metoclopramide B-Chemical 0
in O 0
an O 0
elderly O 0
woman O 0
with O 0
preexisting O 0
complete O 0
left B-Disease 0
bundle I-Disease 0
branch I-Disease 0
block I-Disease 0
. O 0

There O 0
is O 0
a O 0
growing O 0
list O 0
of O 0
drugs O 0
implicated O 0
in O 0
acquired O 0
long B-Disease 0
QT I-Disease 0
syndrome I-Disease 0
and O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
. O 0

However O 0
, O 0
the O 0
torsadogenic O 0
potential O 0
of O 0
metoclopramide B-Chemical 0
, O 0
a O 0
commonly O 0
used O 0
antiemetic O 0
and O 0
prokinetic O 0
drug O 0
, O 0
has O 0
not O 0
been O 0
reported O 0
in O 0
the O 0
literature O 0
, O 0
despite O 0
its O 0
chemical O 0
similarity O 0
to O 0
procainamide B-Chemical 0
. O 0

We O 0
report O 0
on O 0
a O 0
92 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
preexisting O 0
complete O 0
left B-Disease 0
bundle I-Disease 0
branch I-Disease 0
block I-Disease 0
who O 0
developed O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
after O 0
intravenous O 0
and O 0
oral O 0
administration O 0
of O 0
metoclopramide B-Chemical 0
. O 0

This O 0
patient O 0
also O 0
developed O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
when O 0
cisapride B-Chemical 0
and O 0
erythromycin B-Chemical 0
were O 0
given O 0
simultaneously O 0
. O 0

These O 0
two O 0
episodes O 0
were O 0
suppressed O 0
successfully O 0
after O 0
discontinuing O 0
the O 0
offending O 0
drugs O 0
and O 0
administering O 0
class O 0
IB O 0
drugs O 0
. O 0

This O 0
is O 0
the O 0
first O 0
documentation O 0
that O 0
metoclopramide B-Chemical 0
provokes O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
clinically O 0
. O 0

Metoclopramide B-Chemical 0
should O 0
be O 0
used O 0
cautiously O 0
in O 0
patients O 0
with O 0
a O 0
risk O 0
of O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
. O 0

Dopamine B-Chemical 0
D2 O 0
receptor O 0
signaling O 0
controls O 0
neuronal O 0
cell O 0
death O 0
induced O 0
by O 0
muscarinic O 0
and O 0
glutamatergic O 0
drugs O 0
. O 0

Dopamine B-Chemical 0
( O 0
DA B-Chemical 0
) O 0
, O 0
through O 0
D1 O 0
/ O 0
D2 O 0
receptor O 0
- O 0
mediated O 0
signaling O 0
, O 0
plays O 0
a O 0
major O 0
role O 0
in O 0
the O 0
control O 0
of O 0
epileptic B-Disease 0
seizures I-Disease 0
arising O 0
in O 0
the O 0
limbic O 0
system O 0
. O 0

Excitotoxicity B-Disease 0
leading O 0
to O 0
neuronal O 0
cell O 0
death O 0
in O 0
the O 0
affected O 0
areas O 0
is O 0
a O 0
major O 0
consequence O 0
of O 0
seizures B-Disease 0
at O 0
the O 0
cellular O 0
level O 0
. O 0

In O 0
this O 0
respect O 0
, O 0
little O 0
is O 0
known O 0
about O 0
the O 0
role O 0
of O 0
DA B-Chemical 0
receptors O 0
in O 0
the O 0
occurrence O 0
of O 0
epilepsy B-Disease 0
- O 0
induced O 0
neuronal O 0
cell O 0
death O 0
. O 0

Here O 0
we O 0
analyze O 0
the O 0
occurrence O 0
of O 0
seizures B-Disease 0
and O 0
neurotoxicity B-Disease 0
in O 0
D2R O 0
- O 0
/ O 0
- O 0
mice O 0
treated O 0
with O 0
the O 0
cholinergic O 0
agonist O 0
pilocarpine B-Chemical 0
. O 0

We O 0
compared O 0
these O 0
results O 0
with O 0
those O 0
previously O 0
obtained O 0
with O 0
kainic B-Chemical 0
acid I-Chemical 0
( O 0
KA B-Chemical 0
) O 0
, O 0
a O 0
potent O 0
glutamate B-Chemical 0
agonist O 0
. O 0

Importantly O 0
, O 0
D2R O 0
- O 0
/ O 0
- O 0
mice O 0
develop O 0
seizures B-Disease 0
at O 0
doses O 0
of O 0
both O 0
drugs O 0
that O 0
are O 0
not O 0
epileptogenic O 0
for O 0
WT O 0
littermates O 0
and O 0
show O 0
greater O 0
neurotoxicity B-Disease 0
. O 0

However O 0
, O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
result O 0
in O 0
a O 0
more O 0
widespread O 0
neuronal O 0
death O 0
in O 0
both O 0
WT O 0
and O 0
D2R O 0
- O 0
/ O 0
- O 0
brains O 0
in O 0
comparison O 0
to O 0
KA B-Chemical 0
. O 0

Thus O 0
, O 0
the O 0
absence O 0
of O 0
D2R O 0
lowers O 0
the O 0
threshold O 0
for O 0
seizures B-Disease 0
induced O 0
by O 0
both O 0
glutamate B-Chemical 0
and O 0
acetylcholine B-Chemical 0
. O 0

Moreover O 0
, O 0
the O 0
dopaminergic O 0
control O 0
of O 0
epilepsy B-Disease 0
- O 0
induced O 0
neurodegeneration B-Disease 0
seems O 0
to O 0
be O 0
mediated O 0
by O 0
distinct O 0
interactions O 0
of O 0
D2R O 0
signaling O 0
with O 0
these O 0
two O 0
neurotransmitters O 0
. O 0

Steroid B-Chemical 0
structure O 0
and O 0
pharmacological O 0
properties O 0
determine O 0
the O 0
anti O 0
- O 0
amnesic B-Disease 0
effects O 0
of O 0
pregnenolone B-Chemical 0
sulphate I-Chemical 0
in O 0
the O 0
passive O 0
avoidance O 0
task O 0
in O 0
rats O 0
. O 0

Pregnenolone B-Chemical 0
sulphate I-Chemical 0
( O 0
PREGS B-Chemical 0
) O 0
has O 0
generated O 0
interest O 0
as O 0
one O 0
of O 0
the O 0
most O 0
potent O 0
memory O 0
- O 0
enhancing O 0
neurosteroids O 0
to O 0
be O 0
examined O 0
in O 0
rodent O 0
learning O 0
studies O 0
, O 0
with O 0
particular O 0
importance O 0
in O 0
the O 0
ageing O 0
process O 0
. O 0

The O 0
mechanism O 0
by O 0
which O 0
this O 0
endogenous O 0
steroid B-Chemical 0
enhances O 0
memory O 0
formation O 0
is O 0
hypothesized O 0
to O 0
involve O 0
actions O 0
on O 0
glutamatergic O 0
and O 0
GABAergic O 0
systems O 0
. O 0

This O 0
hypothesis O 0
stems O 0
from O 0
findings O 0
that O 0
PREGS B-Chemical 0
is O 0
a O 0
potent O 0
positive O 0
modulator O 0
of 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
receptors O 0
( O 0
NMDARs O 0
) O 0
and O 0
a O 0
negative O 0
modulator O 0
of O 0
gamma B-Chemical 0
- I-Chemical 0
aminobutyric I-Chemical 0
acid I-Chemical 0
( O 0
A O 0
) O 0
receptors O 0
( O 0
GABA B-Chemical 0
( O 0
A O 0
) O 0
Rs O 0
) O 0
. O 0

Moreover O 0
, O 0
PREGS B-Chemical 0
is O 0
able O 0
to O 0
reverse O 0
the O 0
amnesic B-Disease 0
- O 0
like O 0
effects O 0
of O 0
NMDAR O 0
and O 0
GABA B-Chemical 0
( O 0
A O 0
) O 0
R O 0
ligands O 0
. O 0

To O 0
investigate O 0
this O 0
hypothesis O 0
, O 0
the O 0
present O 0
study O 0
in O 0
rats O 0
examined O 0
the O 0
memory O 0
- O 0
altering O 0
abilities O 0
of O 0
structural O 0
analogs O 0
of O 0
PREGS B-Chemical 0
, O 0
which O 0
differ O 0
in O 0
their O 0
modulation O 0
of O 0
NMDAR O 0
and O 0
/ O 0
or O 0
GABA B-Chemical 0
( O 0
A O 0
) O 0
R O 0
function O 0
. O 0

The O 0
analogs O 0
tested O 0
were O 0
: O 0
11 B-Chemical 0
- I-Chemical 0
ketopregnenolone I-Chemical 0
sulphate I-Chemical 0
( O 0
an O 0
agent O 0
that O 0
is O 0
inactive O 0
at O 0
GABA B-Chemical 0
( O 0
A O 0
) O 0
Rs O 0
and O 0
NMDARs O 0
) O 0
, O 0
epipregnanolone B-Chemical 0
( I-Chemical 0
[ I-Chemical 0
3beta I-Chemical 0
- I-Chemical 0
hydroxy I-Chemical 0
- I-Chemical 0
5beta I-Chemical 0
- I-Chemical 0
pregnan I-Chemical 0
- I-Chemical 0
20 I-Chemical 0
- I-Chemical 0
one I-Chemical 0
] I-Chemical 0
sulphate I-Chemical 0
, O 0
an O 0
inhibitor O 0
of O 0
both O 0
GABA B-Chemical 0
( O 0
A O 0
) O 0
Rs O 0
and O 0
NMDARs O 0
) O 0
, O 0
and O 0
a O 0
newly O 0
synthesized O 0
( O 0
- O 0
) O 0
PREGS B-Chemical 0
enantiomer O 0
( O 0
which O 0
is O 0
identical O 0
to O 0
PREGS B-Chemical 0
in O 0
effects O 0
on O 0
GABA B-Chemical 0
( O 0
A O 0
) O 0
Rs O 0
and O 0
NMDARs O 0
) O 0
. O 0

The O 0
memory O 0
- O 0
enhancing O 0
effects O 0
of O 0
PREGS B-Chemical 0
and O 0
its O 0
analogs O 0
were O 0
tested O 0
in O 0
the O 0
passive O 0
avoidance O 0
task O 0
using O 0
the O 0
model O 0
of O 0
scopolamine B-Chemical 0
- O 0
induced O 0
amnesia B-Disease 0
. O 0

Both O 0
PREGS B-Chemical 0
and O 0
its O 0
( O 0
- O 0
) O 0
enantiomer O 0
blocked O 0
the O 0
effects O 0
of O 0
scopolamine B-Chemical 0
. O 0

The O 0
results O 0
show O 0
that O 0
, O 0
unlike O 0
PREGS B-Chemical 0
, O 0
11 B-Chemical 0
- I-Chemical 0
ketopregnenolone I-Chemical 0
sulphate I-Chemical 0
and O 0
epipregnanolone B-Chemical 0
sulphate I-Chemical 0
failed O 0
to O 0
block O 0
the O 0
effect O 0
of O 0
scopolamine B-Chemical 0
, O 0
suggesting O 0
that O 0
altering O 0
the O 0
modulation O 0
of O 0
NMDA B-Chemical 0
receptors O 0
diminishes O 0
the O 0
memory O 0
- O 0
enhancing O 0
effects O 0
of O 0
PREGS B-Chemical 0
. O 0

Moreover O 0
, O 0
enantioselectivity O 0
was O 0
demonstrated O 0
by O 0
the O 0
ability O 0
of O 0
natural O 0
PREGS B-Chemical 0
to O 0
be O 0
an O 0
order O 0
of O 0
magnitude O 0
more O 0
effective O 0
than O 0
its O 0
synthetic O 0
enantiomer O 0
in O 0
reversing O 0
scopolamine B-Chemical 0
- O 0
induced O 0
amnesia B-Disease 0
. O 0

These O 0
results O 0
identify O 0
a O 0
novel O 0
neuropharmacological O 0
site O 0
for O 0
the O 0
modulation O 0
of O 0
memory O 0
processes O 0
by O 0
neuroactive O 0
steroids B-Chemical 0
. O 0

Activation O 0
of O 0
poly B-Chemical 0
( I-Chemical 0
ADP I-Chemical 0
- I-Chemical 0
ribose I-Chemical 0
) I-Chemical 0
polymerase O 0
contributes O 0
to O 0
development O 0
of O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
heart B-Disease 0
failure I-Disease 0
. O 0

Activation O 0
of O 0
the O 0
nuclear O 0
enzyme O 0
poly B-Chemical 0
( I-Chemical 0
ADP I-Chemical 0
- I-Chemical 0
ribose I-Chemical 0
) I-Chemical 0
polymerase O 0
( O 0
PARP O 0
) O 0
by O 0
oxidant O 0
- O 0
mediated O 0
DNA O 0
damage O 0
is O 0
an O 0
important O 0
pathway O 0
of O 0
cell O 0
dysfunction O 0
and O 0
tissue O 0
injury O 0
in O 0
conditions O 0
associated O 0
with O 0
oxidative O 0
stress O 0
. O 0

Increased O 0
oxidative O 0
stress O 0
is O 0
a O 0
major O 0
factor O 0
implicated O 0
in O 0
the O 0
cardiotoxicity B-Disease 0
of O 0
doxorubicin B-Chemical 0
( O 0
DOX B-Chemical 0
) O 0
, O 0
a O 0
widely O 0
used O 0
antitumor O 0
anthracycline B-Chemical 0
antibiotic O 0
. O 0

Thus O 0
, O 0
we O 0
hypothesized O 0
that O 0
the O 0
activation O 0
of O 0
PARP O 0
may O 0
contribute O 0
to O 0
the O 0
DOX B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

Using O 0
a O 0
dual O 0
approach O 0
of O 0
PARP O 0
- O 0
1 O 0
suppression O 0
, O 0
by O 0
genetic O 0
deletion O 0
or O 0
pharmacological O 0
inhibition O 0
with O 0
the O 0
phenanthridinone O 0
PARP O 0
inhibitor O 0
PJ34 B-Chemical 0
, O 0
we O 0
now O 0
demonstrate O 0
the O 0
role O 0
of O 0
PARP O 0
in O 0
the O 0
development O 0
of O 0
cardiac B-Disease 0
dysfunction I-Disease 0
induced O 0
by O 0
DOX B-Chemical 0
. O 0

PARP O 0
- O 0
1 O 0
+ O 0
/ O 0
+ O 0
and O 0
PARP O 0
- O 0
1 O 0
- O 0
/ O 0
- O 0
mice O 0
received O 0
a O 0
single O 0
injection O 0
of O 0
DOX B-Chemical 0
( O 0
25 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
) O 0
. O 0

Five O 0
days O 0
after O 0
DOX B-Chemical 0
administration O 0
, O 0
left O 0
ventricular O 0
performance O 0
was O 0
significantly O 0
depressed O 0
in O 0
PARP O 0
- O 0
1 O 0
+ O 0
/ O 0
+ O 0
mice O 0
, O 0
but O 0
only O 0
to O 0
a O 0
smaller O 0
extent O 0
in O 0
PARP O 0
- O 0
1 O 0
- O 0
/ O 0
- O 0
ones O 0
. O 0

Similar O 0
experiments O 0
were O 0
conducted O 0
in O 0
BALB O 0
/ O 0
c O 0
mice O 0
treated O 0
with O 0
PJ34 B-Chemical 0
or O 0
vehicle O 0
. O 0

Treatment O 0
with O 0
a O 0
PJ34 B-Chemical 0
significantly O 0
improved O 0
cardiac B-Disease 0
dysfunction I-Disease 0
and O 0
increased O 0
the O 0
survival O 0
of O 0
the O 0
animals O 0
. O 0

In O 0
addition O 0
PJ34 B-Chemical 0
significantly O 0
reduced O 0
the O 0
DOX B-Chemical 0
- O 0
induced O 0
increase O 0
in O 0
the O 0
serum O 0
lactate B-Chemical 0
dehydrogenase O 0
and O 0
creatine B-Chemical 0
kinase O 0
activities O 0
but O 0
not O 0
metalloproteinase O 0
activation O 0
in O 0
the O 0
heart O 0
. O 0

Thus O 0
, O 0
PARP O 0
activation O 0
contributes O 0
to O 0
the O 0
cardiotoxicity B-Disease 0
of O 0
DOX B-Chemical 0
. O 0

PARP O 0
inhibitors O 0
may O 0
exert O 0
protective O 0
effects O 0
against O 0
the O 0
development O 0
of O 0
severe O 0
cardiac B-Disease 0
complications I-Disease 0
associated O 0
with O 0
the O 0
DOX B-Chemical 0
treatment O 0
. O 0

Spironolactone B-Chemical 0
: O 0
is O 0
it O 0
a O 0
novel O 0
drug O 0
for O 0
the O 0
prevention O 0
of O 0
amphotericin B-Chemical 0
B I-Chemical 0
- O 0
related O 0
hypokalemia B-Disease 0
in O 0
cancer B-Disease 0
patients O 0
? O 0

OBJECTIVE O 0
: O 0
Nephrotoxicity B-Disease 0
is O 0
the O 0
major O 0
adverse O 0
effect O 0
of O 0
amphotericin B-Chemical 0
B I-Chemical 0
( O 0
AmB B-Chemical 0
) O 0
, O 0
often O 0
limiting O 0
administration O 0
of O 0
full O 0
dosage O 0
. O 0

Selective O 0
distal O 0
tubular O 0
epithelial O 0
toxicity B-Disease 0
seems O 0
to O 0
be O 0
responsible O 0
for O 0
the O 0
profound O 0
potassium B-Chemical 0
wasting O 0
that O 0
is O 0
a O 0
major O 0
clinical O 0
side O 0
effect O 0
of O 0
treatment O 0
with O 0
AmB B-Chemical 0
. O 0

Potassium B-Chemical 0
depletion O 0
also O 0
potentiates O 0
the O 0
tubular O 0
toxicity B-Disease 0
of O 0
AmB B-Chemical 0
. O 0

This O 0
study O 0
was O 0
designed O 0
to O 0
assess O 0
the O 0
ability O 0
of O 0
spironolactone B-Chemical 0
to O 0
reduce O 0
potassium B-Chemical 0
requirements O 0
and O 0
to O 0
prevent O 0
hypokalemia B-Disease 0
in O 0
neutropenic B-Disease 0
patients O 0
on O 0
AmB B-Chemical 0
treatment O 0
. O 0

METHODS O 0
: O 0
In O 0
this O 0
study O 0
26 O 0
patients O 0
with O 0
various O 0
hematological B-Disease 0
disorders I-Disease 0
were O 0
randomized O 0
to O 0
receive O 0
either O 0
intravenous O 0
AmB B-Chemical 0
alone O 0
or O 0
AmB B-Chemical 0
and O 0
oral O 0
spironolactone B-Chemical 0
100 O 0
mg O 0
twice O 0
daily O 0
when O 0
developing O 0
a O 0
proven O 0
or O 0
suspected O 0
fungal B-Disease 0
infection I-Disease 0
. O 0

RESULTS O 0
: O 0
Patients O 0
receiving O 0
concomitant O 0
AmB B-Chemical 0
and O 0
spironolactone B-Chemical 0
had O 0
significantly O 0
higher O 0
plasma O 0
potassium B-Chemical 0
levels O 0
than O 0
those O 0
receiving O 0
AmB B-Chemical 0
alone O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
0027 O 0
) O 0
. O 0

Those O 0
patients O 0
receiving O 0
AmB B-Chemical 0
and O 0
spironolactone B-Chemical 0
required O 0
significantly O 0
less O 0
potassium B-Chemical 0
supplementation O 0
to O 0
maintain O 0
their O 0
plasma O 0
potassium B-Chemical 0
within O 0
the O 0
normal O 0
range O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
022 O 0
) O 0
. O 0

Moreover O 0
, O 0
urinary O 0
potassium B-Chemical 0
losses O 0
were O 0
significantly O 0
less O 0
in O 0
patients O 0
receiving O 0
AmB B-Chemical 0
and O 0
spironolactone B-Chemical 0
than O 0
those O 0
receiving O 0
AmB B-Chemical 0
alone O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
040 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
This O 0
study O 0
showed O 0
that O 0
spironolactone B-Chemical 0
can O 0
reduce O 0
potassium B-Chemical 0
requirements O 0
and O 0
prevent O 0
hypokalemia B-Disease 0
by O 0
reducing O 0
urinary O 0
potassium B-Chemical 0
loss O 0
in O 0
neutropenic B-Disease 0
patients O 0
on O 0
AmB B-Chemical 0
treatment O 0
. O 0

Erectile B-Disease 0
dysfunction I-Disease 0
occurs O 0
following O 0
substantia O 0
nigra O 0
lesions O 0
in O 0
the O 0
rat O 0
. O 0

Erectile O 0
function O 0
was O 0
assessed O 0
6 O 0
weeks O 0
following O 0
uni O 0
- O 0
and O 0
bilateral O 0
injections O 0
of O 0
6 B-Chemical 0
- I-Chemical 0
hydroxydopamine I-Chemical 0
in O 0
the O 0
substantia O 0
nigra O 0
nucleus O 0
of O 0
the O 0
brain O 0
. O 0

Behavioral O 0
apomorphine B-Chemical 0
- O 0
induced O 0
penile O 0
erections O 0
were O 0
reduced O 0
( O 0
5 O 0
/ O 0
8 O 0
) O 0
and O 0
increased O 0
( O 0
3 O 0
/ O 0
8 O 0
) O 0
in O 0
uni O 0
- O 0
and O 0
bilateral O 0
lesioned O 0
animals O 0
. O 0

Intracavernous O 0
pressures O 0
, O 0
following O 0
electrical O 0
stimulation O 0
of O 0
the O 0
cavernous O 0
nerve O 0
, O 0
decreased O 0
in O 0
lesioned O 0
animals O 0
. O 0

Lesions O 0
of O 0
the O 0
substantia O 0
nigra O 0
were O 0
confirmed O 0
by O 0
histology O 0
. O 0

Concentration O 0
of O 0
dopamine B-Chemical 0
and O 0
its O 0
metabolites O 0
were O 0
decreased O 0
in O 0
the O 0
striatum O 0
of O 0
substantia O 0
nigra O 0
lesioned O 0
rats O 0
. O 0

Lesions O 0
of O 0
the O 0
substantia O 0
nigra O 0
are O 0
therefore O 0
associated O 0
with O 0
erectile B-Disease 0
dysfunction I-Disease 0
in O 0
rats O 0
and O 0
may O 0
serve O 0
as O 0
a O 0
model O 0
to O 0
study O 0
erectile B-Disease 0
dysfunction I-Disease 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

Nicotine B-Chemical 0
potentiation O 0
of O 0
morphine B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
in O 0
mice O 0
. O 0

In O 0
the O 0
present O 0
study O 0
, O 0
effects O 0
of O 0
nicotine B-Chemical 0
on O 0
catalepsy B-Disease 0
induced O 0
by O 0
morphine B-Chemical 0
in O 0
mice O 0
have O 0
been O 0
investigated O 0
. O 0

Morphine B-Chemical 0
but O 0
not O 0
nicotine B-Chemical 0
induced O 0
a O 0
dose O 0
- O 0
dependent O 0
catalepsy B-Disease 0
. O 0

The O 0
response O 0
of O 0
morphine B-Chemical 0
was O 0
potentiated O 0
by O 0
nicotine B-Chemical 0
. O 0

Intraperitoneal O 0
administration O 0
of O 0
atropine B-Chemical 0
, O 0
naloxone B-Chemical 0
, O 0
mecamylamine B-Chemical 0
, O 0
and O 0
hexamethonium B-Chemical 0
to O 0
mice O 0
reduced O 0
catalepsy B-Disease 0
induced O 0
by O 0
a O 0
combination O 0
of O 0
morphine B-Chemical 0
with O 0
nicotine B-Chemical 0
. O 0

Intracerebroventricular O 0
injection O 0
of O 0
atropine B-Chemical 0
, O 0
hexamethonium B-Chemical 0
, O 0
and O 0
naloxone B-Chemical 0
also O 0
decreased O 0
catalepsy B-Disease 0
induced O 0
by O 0
morphine B-Chemical 0
plus O 0
nicotine B-Chemical 0
. O 0

Intraperitoneal O 0
administration O 0
of O 0
atropine B-Chemical 0
, O 0
but O 0
not O 0
intraperitoneal O 0
or O 0
intracerebroventricular O 0
injection O 0
of O 0
hexamethonium B-Chemical 0
, O 0
decreased O 0
the O 0
effect O 0
of O 0
a O 0
single O 0
dose O 0
of O 0
morphine B-Chemical 0
. O 0

It O 0
was O 0
concluded O 0
that O 0
morphine B-Chemical 0
catalepsy B-Disease 0
can O 0
be O 0
elicited O 0
by O 0
opioid O 0
and O 0
cholinergic O 0
receptors O 0
, O 0
and O 0
the O 0
potentiation O 0
of O 0
morphine B-Chemical 0
induced O 0
by O 0
nicotine B-Chemical 0
may O 0
also O 0
be O 0
mediated O 0
through O 0
cholinergic O 0
receptor O 0
mechanisms O 0
. O 0

Force O 0
overflow O 0
and O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

We O 0
assessed O 0
force O 0
coordination O 0
of O 0
the O 0
hand O 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
and O 0
its O 0
relationship O 0
to O 0
motor O 0
complications O 0
of O 0
levodopa B-Chemical 0
therapy O 0
, O 0
particularly O 0
to O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
( O 0
LID B-Disease 0
) O 0
. O 0

We O 0
studied O 0
two O 0
groups O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
patients O 0
with O 0
( O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
+ O 0
LID B-Disease 0
, O 0
n O 0
= O 0
23 O 0
) O 0
and O 0
without O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
( O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
- O 0
LID B-Disease 0
, O 0
n O 0
= O 0
10 O 0
) O 0
, O 0
and O 0
age O 0
- O 0
matched O 0
healthy O 0
controls O 0
. O 0

The O 0
motor O 0
score O 0
of 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
, O 0
a O 0
dyskinesia B-Disease 0
score O 0
and O 0
force O 0
in O 0
a O 0
grip O 0
- O 0
lift O 0
paradigm O 0
were O 0
assessed O 0
ON O 0
and O 0
OFF O 0
levodopa B-Chemical 0
. O 0

A O 0
pathological O 0
increase O 0
of O 0
forces O 0
was O 0
seen O 0
in O 0
ON O 0
- O 0
state O 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
+ O 0
LID B-Disease 0
only O 0
. O 0

In O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
+ O 0
LID B-Disease 0
, O 0
the O 0
force O 0
involved O 0
in O 0
pressing O 0
down O 0
the O 0
object O 0
before O 0
lifting O 0
was O 0
significantly O 0
increased O 0
by O 0
levodopa B-Chemical 0
( O 0
by O 0
61 O 0
% O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

An O 0
overshooting O 0
of O 0
peak O 0
grip O 0
force O 0
by O 0
51 O 0
% O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
and O 0
of O 0
static O 0
grip O 0
force O 0
by O 0
45 O 0
% O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
was O 0
observed O 0
in O 0
the O 0
ON O 0
- O 0
compared O 0
with O 0
the O 0
OFF O 0
- O 0
drug O 0
condition O 0
. O 0

In O 0
contrast O 0
, O 0
no O 0
excessive O 0
force O 0
was O 0
found O 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
- O 0
LID B-Disease 0
. O 0

Peak O 0
grip O 0
force O 0
in O 0
ON O 0
- O 0
state O 0
was O 0
140 O 0
% O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
higher O 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
+ O 0
LID B-Disease 0
than O 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
- O 0
LID B-Disease 0
, O 0
while O 0
static O 0
grip O 0
force O 0
was O 0
increased O 0
by O 0
138 O 0
% O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
between O 0
groups O 0
. O 0

Severity O 0
of O 0
peak O 0
- O 0
dose O 0
dyskinesias B-Disease 0
was O 0
strongly O 0
correlated O 0
with O 0
grip O 0
force O 0
in O 0
ON O 0
- O 0
state O 0
( O 0
r O 0
= O 0
0 O 0
. O 0
79 O 0
with O 0
peak O 0
force O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

No O 0
correlation O 0
was O 0
observed O 0
between O 0
forces O 0
and O 0
the O 0
motor O 0
score O 0
as O 0
well O 0
as O 0
with O 0
the O 0
daily O 0
dose O 0
of O 0
dopaminergic O 0
medication O 0
. O 0

Force O 0
excess O 0
was O 0
only O 0
observed O 0
in O 0
patients O 0
with O 0
LID B-Disease 0
and O 0
motor O 0
fluctuations O 0
. O 0

A O 0
close O 0
relationship O 0
was O 0
seen O 0
between O 0
the O 0
overshooting O 0
of O 0
forces O 0
and O 0
dyskinesias B-Disease 0
in O 0
the O 0
ON O 0
- O 0
drug O 0
condition O 0
. O 0

We O 0
postulate O 0
that O 0
both O 0
LID B-Disease 0
and O 0
grip O 0
force O 0
excess O 0
share O 0
common O 0
pathophysiological O 0
mechanisms O 0
related O 0
to O 0
motor O 0
fluctuations O 0
. O 0

Behavioral O 0
effects O 0
of O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
on O 0
reserpine B-Chemical 0
- O 0
treated O 0
mice O 0
. O 0

The O 0
effects O 0
of O 0
dizocilpine B-Chemical 0
( O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
) O 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
were O 0
studied O 0
on O 0
dopamine B-Chemical 0
- O 0
related O 0
behaviors O 0
induced O 0
by O 0
reserpine B-Chemical 0
treatments O 0
. O 0

This O 0
study O 0
focuses O 0
on O 0
behavioral O 0
syndromes O 0
that O 0
may O 0
used O 0
as O 0
models O 0
for O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
, O 0
or O 0
tardive B-Disease 0
dyskinesia I-Disease 0
, O 0
and O 0
its O 0
response O 0
after O 0
glutamatergic O 0
blockage O 0
. O 0

Reserpine B-Chemical 0
( O 0
1 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
administered O 0
once O 0
every O 0
other O 0
day O 0
for O 0
4 O 0
days O 0
, O 0
produced O 0
increases O 0
in O 0
orofacial B-Disease 0
dyskinesia I-Disease 0
, O 0
tongue O 0
protrusion O 0
and O 0
vacuous O 0
chewing O 0
in O 0
mice O 0
, O 0
which O 0
are O 0
signs O 0
indicative O 0
of O 0
tardive B-Disease 0
dyskinesia I-Disease 0
. O 0

Reserpine B-Chemical 0
also O 0
produced O 0
tremor B-Disease 0
and O 0
catalepsy B-Disease 0
, O 0
which O 0
are O 0
signs O 0
suggestive O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
administered O 0
30 O 0
min O 0
before O 0
the O 0
observation O 0
test O 0
, O 0
prevented O 0
the O 0
vacuous O 0
chewing O 0
movements O 0
, O 0
tongue O 0
protrusions O 0
and O 0
catalepsy B-Disease 0
induced O 0
by O 0
reserpine B-Chemical 0
. O 0

However O 0
, O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
injection O 0
produced O 0
a O 0
significant O 0
increase O 0
of O 0
tremor B-Disease 0
in O 0
reserpine B-Chemical 0
- O 0
treated O 0
mice O 0
. O 0

Reserpine B-Chemical 0
( O 0
1 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
administered O 0
90 O 0
min O 0
before O 0
the O 0
test O 0
and O 0
followed O 0
by O 0
apomophine B-Chemical 0
injection O 0
( O 0
0 O 0
. O 0
1 O 0
mg O 0
/ O 0
kg O 0
) O 0
5 O 0
min O 0
before O 0
the O 0
test O 0
, O 0
did O 0
not O 0
produce O 0
oral B-Disease 0
dyskinesia I-Disease 0
in O 0
mice O 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
reserpine B-Chemical 0
induced O 0
increases O 0
in O 0
tremor B-Disease 0
and O 0
catalepsy B-Disease 0
compared O 0
to O 0
control O 0
mice O 0
. O 0

MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
mg O 0
/ O 0
kg O 0
) O 0
administration O 0
attenuated O 0
the O 0
catalepsy B-Disease 0
and O 0
tremor B-Disease 0
induced O 0
by O 0
reserpine B-Chemical 0
. O 0

Pretreatment O 0
with O 0
reserpine B-Chemical 0
( O 0
1 O 0
mg O 0
/ O 0
kg O 0
) O 0
24 O 0
h O 0
before O 0
the O 0
observation O 0
test O 0
produced O 0
increases O 0
in O 0
vacuous O 0
chewing O 0
movements O 0
and O 0
tongue O 0
protrusion O 0
, O 0
as O 0
well O 0
as O 0
increases O 0
in O 0
tremor B-Disease 0
and O 0
catalepsy B-Disease 0
, O 0
whereas O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
mg O 0
/ O 0
kg O 0
) O 0
injection O 0
90 O 0
min O 0
before O 0
the O 0
test O 0
reversed O 0
the O 0
effects O 0
of O 0
reserpine B-Chemical 0
. O 0

These O 0
results O 0
show O 0
that O 0
reserpine B-Chemical 0
produces O 0
different O 0
and O 0
abnormal B-Disease 0
movements I-Disease 0
, O 0
which O 0
are O 0
related O 0
to O 0
dose O 0
and O 0
schedule O 0
employed O 0
and O 0
can O 0
be O 0
considered O 0
as O 0
parkinsonian B-Disease 0
- O 0
like O 0
and O 0
tardive B-Disease 0
dsykinesia I-Disease 0
signs O 0
. O 0

The O 0
glutamatergic O 0
blockage O 0
produced O 0
by O 0
NMDA B-Chemical 0
can O 0
restore O 0
these O 0
signs O 0
, O 0
such O 0
as O 0
vacuous O 0
chewing O 0
movements O 0
, O 0
tongue O 0
protrusions O 0
, O 0
catalepsy B-Disease 0
and O 0
tremor B-Disease 0
according O 0
to O 0
the O 0
employed O 0
model O 0
. O 0

Risperidone B-Chemical 0
- O 0
associated O 0
, O 0
benign O 0
transient O 0
visual B-Disease 0
disturbances I-Disease 0
in O 0
schizophrenic B-Disease 0
patients O 0
with O 0
a O 0
past O 0
history O 0
of O 0
LSD B-Chemical 0
abuse O 0
. O 0

Two O 0
schizophrenic B-Disease 0
patients O 0
, O 0
who O 0
had O 0
a O 0
prior O 0
history O 0
of O 0
LSD B-Chemical 0
abuse O 0
and O 0
who O 0
had O 0
previously O 0
developed O 0
EPS B-Disease 0
with O 0
classic O 0
antipsychotics O 0
, O 0
were O 0
successfully O 0
treated O 0
with O 0
risperidone B-Chemical 0
. O 0

They O 0
both O 0
reported O 0
short O 0
episodes O 0
of O 0
transient O 0
visual B-Disease 0
disturbances I-Disease 0
, O 0
which O 0
appeared O 0
immediately O 0
after O 0
starting O 0
treatment O 0
with O 0
risperidone B-Chemical 0
. O 0

This O 0
imagery O 0
resembled O 0
visual B-Disease 0
disturbances I-Disease 0
previously O 0
experienced O 0
as O 0
" O 0
flashbacks O 0
" O 0
related O 0
to O 0
prior O 0
LSD B-Chemical 0
consumption O 0
. O 0

Risperidone B-Chemical 0
administration O 0
was O 0
continued O 0
and O 0
the O 0
visual B-Disease 0
disturbances I-Disease 0
gradually O 0
wore O 0
off O 0
. O 0

During O 0
a O 0
six O 0
- O 0
month O 0
follow O 0
- O 0
up O 0
period O 0
, O 0
there O 0
was O 0
no O 0
recurrence O 0
of O 0
visual B-Disease 0
disturbances I-Disease 0
. O 0

This O 0
phenomenon O 0
may O 0
be O 0
interpreted O 0
as O 0
a O 0
benign O 0
, O 0
short O 0
- O 0
term O 0
and O 0
self O 0
- O 0
limiting O 0
side O 0
effect O 0
which O 0
does O 0
not O 0
contraindicate O 0
the O 0
use O 0
of O 0
risperidone B-Chemical 0
or O 0
interfere O 0
with O 0
treatment O 0
. O 0

Conclusions O 0
based O 0
on O 0
two O 0
case O 0
reports O 0
should O 0
be O 0
taken O 0
with O 0
appropriate O 0
caution O 0
. O 0

Topiramate B-Chemical 0
- O 0
induced O 0
nephrolithiasis B-Disease 0
. O 0

Topiramate B-Chemical 0
is O 0
a O 0
recently O 0
developed O 0
antiepileptic O 0
medication O 0
that O 0
is O 0
becoming O 0
more O 0
widely O 0
prescribed O 0
because O 0
of O 0
its O 0
efficacy O 0
in O 0
treating O 0
refractory B-Disease 0
seizures I-Disease 0
. O 0

Urologists O 0
should O 0
be O 0
aware O 0
that O 0
this O 0
medication O 0
can O 0
cause O 0
metabolic B-Disease 0
acidosis I-Disease 0
in O 0
patients O 0
secondary O 0
to O 0
inhibition O 0
of O 0
carbonic O 0
anhydrase O 0
. O 0

In O 0
addition O 0
, O 0
a O 0
distal O 0
tubular O 0
acidification O 0
defect O 0
may O 0
result O 0
, O 0
thus O 0
impairing O 0
the O 0
normal O 0
compensatory O 0
drop O 0
in O 0
urine O 0
pH O 0
. O 0

These O 0
factors O 0
can O 0
lead O 0
to O 0
the O 0
development O 0
of O 0
calcium B-Chemical 0
phosphate I-Chemical 0
nephrolithiasis B-Disease 0
. O 0

We O 0
report O 0
the O 0
first O 0
two O 0
cases O 0
of O 0
topiramate B-Chemical 0
- O 0
induced O 0
nephrolithiasis B-Disease 0
in O 0
the O 0
urologic O 0
literature O 0
. O 0

Ketamine B-Chemical 0
in O 0
war O 0
/ O 0
tropical O 0
surgery O 0
( O 0
a O 0
final O 0
tribute O 0
to O 0
the O 0
racemic O 0
mixture O 0
) O 0
. O 0

A O 0
technique O 0
of O 0
continuous O 0
intravenous O 0
anaesthesia O 0
with O 0
ketamine B-Chemical 0
was O 0
used O 0
successfully O 0
during O 0
the O 0
Somalia O 0
civil O 0
war O 0
in O 0
1994 O 0
and O 0
in O 0
north O 0
Uganda O 0
in O 0
1999 O 0
for O 0
64 O 0
operations O 0
in O 0
62 O 0
patients O 0
, O 0
aged O 0
from O 0
6 O 0
weeks O 0
to O 0
70 O 0
years O 0
, O 0
undergoing O 0
limb O 0
and O 0
abdominal O 0
surgery O 0
including O 0
caesarian O 0
sections O 0
and O 0
interventions O 0
in O 0
neonates O 0
. O 0

Operations O 0
lasting O 0
up O 0
to O 0
2h O 0
could O 0
be O 0
performed O 0
in O 0
the O 0
absence O 0
of O 0
sophisticated O 0
equipment O 0
such O 0
as O 0
pulse O 0
oximeters O 0
or O 0
ventilators O 0
in O 0
patients O 0
on O 0
spontaneous O 0
ventilation O 0
breathing O 0
air O 0
/ O 0
oxygen B-Chemical 0
only O 0
. O 0

After O 0
premedication O 0
with O 0
diazepam B-Chemical 0
, O 0
glycopyrrolate B-Chemical 0
and O 0
local O 0
anaesthesia O 0
, O 0
and O 0
induction O 0
with O 0
standard O 0
doses O 0
of O 0
ketamine B-Chemical 0
, O 0
a O 0
maintenance O 0
dose O 0
of O 0
10 O 0
- O 0
20 O 0
microg O 0
/ O 0
kg O 0
/ O 0
min O 0
of O 0
ketamine B-Chemical 0
proved O 0
safe O 0
and O 0
effective O 0
. O 0

Emphasis O 0
was O 0
placed O 0
on O 0
bedside O 0
clinical O 0
monitoring O 0
, O 0
relying O 0
heavily O 0
on O 0
the O 0
heart O 0
rate O 0
. O 0

Diazepam B-Chemical 0
, O 0
unless O 0
contraindicated O 0
or O 0
risky O 0
, O 0
remains O 0
the O 0
only O 0
necessary O 0
complementary O 0
drug O 0
to O 0
ketamine B-Chemical 0
as O 0
it O 0
buffers O 0
its O 0
cardiovascular O 0
response O 0
and O 0
decreases O 0
the O 0
duration O 0
and O 0
intensity O 0
of O 0
operative O 0
and O 0
postoperative O 0
hallucinations B-Disease 0
. O 0

Local O 0
anaesthetic O 0
blocks O 0
were O 0
useful O 0
in O 0
decreasing O 0
the O 0
requirement O 0
for O 0
postoperative O 0
analgesia B-Disease 0
. O 0

An O 0
antisialogue O 0
was O 0
usually O 0
unnecessary O 0
in O 0
operations O 0
lasting O 0
up O 0
to O 0
2 O 0
h O 0
, O 0
glycopyrrolate B-Chemical 0
being O 0
the O 0
best O 0
choice O 0
for O 0
its O 0
lowest O 0
psychotropic O 0
and O 0
chronotropic O 0
effects O 0
, O 0
especially O 0
in O 0
a O 0
hot O 0
climate O 0
. O 0

Experience O 0
in O 0
war O 0
/ O 0
tropical O 0
settings O 0
suggests O 0
this O 0
technique O 0
could O 0
be O 0
useful O 0
in O 0
civilian O 0
contexts O 0
such O 0
as O 0
outdoor O 0
life O 0
- O 0
saving O 0
emergency O 0
surgery O 0
or O 0
in O 0
mass O 0
casualties O 0
where O 0
, O 0
e O 0
. O 0
g O 0
. O 0
amputation O 0
and O 0
rapid O 0
extrication O 0
were O 0
required O 0
. O 0

Intravenous O 0
ribavirin B-Chemical 0
treatment O 0
for O 0
severe O 0
adenovirus B-Disease 0
disease I-Disease 0
in O 0
immunocompromised O 0
children O 0
. O 0

BACKGROUND O 0
: O 0
Adenovirus O 0
is O 0
an O 0
important O 0
cause O 0
of O 0
morbidity O 0
and O 0
mortality O 0
in O 0
the O 0
immunocompromised O 0
host O 0
. O 0

The O 0
incidence O 0
of O 0
severe O 0
adenovirus B-Disease 0
disease I-Disease 0
in O 0
pediatrics O 0
is O 0
increasing O 0
in O 0
association O 0
with O 0
growing O 0
numbers O 0
of O 0
immunocompromised O 0
children O 0
, O 0
where O 0
case O 0
fatality O 0
rates O 0
as O 0
high O 0
as O 0
50 O 0
% O 0
to O 0
80 O 0
% O 0
have O 0
been O 0
reported O 0
. O 0

There O 0
are O 0
no O 0
approved O 0
antiviral O 0
agents O 0
with O 0
proven O 0
efficacy O 0
for O 0
the O 0
treatment O 0
of O 0
severe O 0
adenovirus B-Disease 0
disease I-Disease 0
, O 0
nor O 0
are O 0
there O 0
any O 0
prospective O 0
randomized O 0
, O 0
controlled O 0
trials O 0
of O 0
potentially O 0
useful O 0
anti O 0
- O 0
adenovirus O 0
therapies O 0
. O 0

Apparent O 0
clinical O 0
success O 0
in O 0
the O 0
treatment O 0
of O 0
severe O 0
adenovirus B-Disease 0
disease I-Disease 0
is O 0
limited O 0
to O 0
a O 0
few O 0
case O 0
reports O 0
and O 0
small O 0
series O 0
. O 0

Experience O 0
is O 0
greatest O 0
with O 0
intravenous O 0
ribavirin B-Chemical 0
and O 0
cidofovir B-Chemical 0
. O 0

Ribavirin B-Chemical 0
, O 0
a O 0
guanosine B-Chemical 0
analogue O 0
, O 0
has O 0
broad O 0
antiviral O 0
activity O 0
against O 0
both O 0
RNA O 0
and O 0
DNA O 0
viruses O 0
, O 0
including O 0
documented O 0
activity O 0
against O 0
adenovirus O 0
in O 0
vitro O 0
. O 0

Ribavirin B-Chemical 0
is O 0
licensed O 0
in O 0
aerosol O 0
form O 0
for O 0
the O 0
treatment O 0
of O 0
respiratory B-Disease 0
syncytial I-Disease 0
virus I-Disease 0
infection I-Disease 0
, O 0
and O 0
orally O 0
in O 0
combination O 0
with O 0
interferon O 0
to O 0
treat O 0
hepatitis B-Disease 0
C I-Disease 0
. O 0

Intravenous O 0
ribavirin B-Chemical 0
is O 0
the O 0
treatment O 0
of O 0
choice O 0
for O 0
infection B-Disease 0
with I-Disease 0
hemorrhagic I-Disease 0
fever I-Disease 0
viruses I-Disease 0
. O 0

The O 0
most O 0
common O 0
adverse O 0
effect O 0
of O 0
intravenous O 0
ribavirin B-Chemical 0
is O 0
reversible O 0
mild O 0
anemia B-Disease 0
. O 0

The O 0
use O 0
of O 0
cidofovir B-Chemical 0
in O 0
severe O 0
adenovirus B-Disease 0
infection I-Disease 0
has O 0
been O 0
limited O 0
by O 0
adverse O 0
effects O 0
, O 0
the O 0
most O 0
significant O 0
of O 0
which O 0
is O 0
nephrotoxicity B-Disease 0
. O 0

OBJECTIVE O 0
: O 0
We O 0
report O 0
our O 0
experience O 0
with O 0
intravenous O 0
ribavirin B-Chemical 0
therapy O 0
for O 0
severe O 0
adenovirus B-Disease 0
disease I-Disease 0
in O 0
a O 0
series O 0
of O 0
immunocompromised O 0
children O 0
and O 0
review O 0
the O 0
literature O 0
. O 0

DESIGN O 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
of O 0
5 O 0
children O 0
treated O 0
with O 0
intravenous O 0
ribavirin B-Chemical 0
for O 0
documented O 0
severe O 0
adenovirus B-Disease 0
disease I-Disease 0
. O 0

Two O 0
patients O 0
developed O 0
adenovirus O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
after O 0
cardiac O 0
and O 0
bone O 0
marrow O 0
transplants O 0
, O 0
respectively O 0
. O 0

The O 0
bone O 0
marrow O 0
transplant O 0
patient O 0
also O 0
received O 0
intravenous O 0
cidofovir B-Chemical 0
for O 0
progressive O 0
disseminated O 0
disease O 0
. O 0

An O 0
additional O 0
3 O 0
children O 0
developed O 0
adenovirus B-Disease 0
pneumonia I-Disease 0
; O 0
2 O 0
were O 0
neonates O 0
, O 0
1 O 0
of O 0
whom O 0
had O 0
partial O 0
DiGeorge B-Disease 0
syndrome I-Disease 0
. O 0

The O 0
remaining O 0
infant O 0
had O 0
recently O 0
undergone O 0
a O 0
cardiac O 0
transplant O 0
. O 0

Intravenous O 0
ribavirin B-Chemical 0
was O 0
administered O 0
on O 0
a O 0
compassionate O 0
- O 0
use O 0
protocol O 0
. O 0

RESULTS O 0
: O 0
Complete O 0
clinical O 0
recovery O 0
followed O 0
later O 0
by O 0
viral O 0
clearance O 0
was O 0
observed O 0
in O 0
2 O 0
children O 0
: O 0
the O 0
cardiac O 0
transplant O 0
recipient O 0
with O 0
adenovirus O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
and O 0
the O 0
immunocompetent O 0
neonate O 0
with O 0
adenovirus B-Disease 0
pneumonia I-Disease 0
. O 0

The O 0
remaining O 0
3 O 0
children O 0
died O 0
of O 0
adenovirus B-Disease 0
disease I-Disease 0
. O 0

Intravenous O 0
ribavirin B-Chemical 0
therapy O 0
was O 0
well O 0
tolerated O 0
. O 0

Use O 0
of O 0
cidofovir B-Chemical 0
in O 0
1 O 0
child O 0
was O 0
associated O 0
with O 0
progressive B-Disease 0
renal I-Disease 0
failure I-Disease 0
and O 0
neutropenia B-Disease 0
. O 0

DISCUSSION O 0
: O 0
Our O 0
series O 0
of O 0
patients O 0
is O 0
representative O 0
of O 0
the O 0
spectrum O 0
of O 0
immunocompromised O 0
children O 0
at O 0
greatest O 0
risk O 0
for O 0
severe O 0
adenovirus B-Disease 0
disease I-Disease 0
, O 0
namely O 0
solid O 0
- O 0
organ O 0
and O 0
bone O 0
marrow O 0
transplant O 0
recipients O 0
, O 0
neonates O 0
, O 0
and O 0
children O 0
with O 0
immunodeficiency B-Disease 0
. O 0

Although O 0
intravenous O 0
ribavirin B-Chemical 0
was O 0
not O 0
effective O 0
for O 0
all O 0
children O 0
with O 0
severe O 0
adenovirus B-Disease 0
disease I-Disease 0
in O 0
this O 0
series O 0
or O 0
in O 0
the O 0
literature O 0
, O 0
therapy O 0
is O 0
unlikely O 0
to O 0
be O 0
of O 0
benefit O 0
if O 0
begun O 0
late O 0
in O 0
the O 0
course O 0
of O 0
the O 0
infection B-Disease 0
. O 0

Early O 0
identification O 0
, O 0
eg O 0
by O 0
polymerase O 0
chain O 0
reaction O 0
of O 0
those O 0
patients O 0
at O 0
risk O 0
of O 0
disseminated O 0
adenovirus B-Disease 0
disease I-Disease 0
may O 0
permit O 0
earlier O 0
antiviral O 0
treatment O 0
and O 0
better O 0
evaluation O 0
of O 0
therapeutic O 0
response O 0
. O 0

CONCLUSIONS O 0
: O 0
Two O 0
of O 0
5 O 0
children O 0
with O 0
severe O 0
adenovirus B-Disease 0
disease I-Disease 0
treated O 0
with O 0
intravenous O 0
ribavirin B-Chemical 0
recovered O 0
. O 0

The O 0
availability O 0
of O 0
newer O 0
rapid O 0
diagnostic O 0
techniques O 0
, O 0
such O 0
as O 0
polymerase O 0
chain O 0
reaction O 0
, O 0
may O 0
make O 0
earlier O 0
, O 0
more O 0
effective O 0
treatment O 0
of O 0
adenovirus B-Disease 0
infection I-Disease 0
possible O 0
. O 0

Given O 0
the O 0
seriousness O 0
and O 0
increasing O 0
prevalence O 0
of O 0
adenovirus B-Disease 0
disease I-Disease 0
in O 0
certain O 0
hosts O 0
, O 0
especially O 0
children O 0
, O 0
a O 0
large O 0
, O 0
multicenter O 0
clinical O 0
trial O 0
of O 0
potentially O 0
useful O 0
anti O 0
- O 0
adenoviral O 0
therapies O 0
, O 0
such O 0
as O 0
intravenous O 0
ribavirin B-Chemical 0
, O 0
is O 0
clearly O 0
required O 0
to O 0
demonstrate O 0
the O 0
most O 0
effective O 0
and O 0
least O 0
toxic O 0
therapy O 0
. O 0

Delayed O 0
asystolic B-Disease 0
cardiac B-Disease 0
arrest I-Disease 0
after O 0
diltiazem B-Chemical 0
overdose B-Disease 0
; O 0
resuscitation O 0
with O 0
high O 0
dose O 0
intravenous O 0
calcium B-Chemical 0
. O 0

A O 0
51 O 0
year O 0
old O 0
man O 0
took O 0
a O 0
mixed O 0
overdose B-Disease 0
including O 0
1 O 0
. O 0
8 O 0
- O 0
3 O 0
. O 0
6 O 0
g O 0
of O 0
diltiazem B-Chemical 0
, O 0
paracetamol B-Chemical 0
, O 0
aspirin B-Chemical 0
, O 0
isosorbide B-Chemical 0
nitrate B-Chemical 0
, O 0
and O 0
alcohol B-Chemical 0
. O 0

He O 0
initially O 0
presented O 0
to O 0
hospital O 0
after O 0
six O 0
hours O 0
with O 0
mild O 0
hypotension B-Disease 0
and O 0
was O 0
treated O 0
with O 0
activated O 0
charcoal O 0
and O 0
intravenous O 0
fluids O 0
. O 0

Eighteen O 0
hours O 0
after O 0
the O 0
overdose B-Disease 0
he O 0
had O 0
two O 0
generalised O 0
tonic B-Disease 0
- I-Disease 0
clonic I-Disease 0
seizures I-Disease 0
. O 0

The O 0
patient O 0
remained O 0
unresponsive O 0
with O 0
junctional O 0
bradycardia B-Disease 0
, O 0
unrecordable O 0
blood O 0
pressure O 0
, O 0
and O 0
then O 0
became O 0
asystolic B-Disease 0
. O 0

He O 0
was O 0
resuscitated O 0
with O 0
high O 0
dose O 0
( O 0
13 O 0
. O 0
5 O 0
g O 0
) O 0
intravenous O 0
calcium B-Chemical 0
and O 0
adrenaline B-Chemical 0
( O 0
epinephrine B-Chemical 0
) O 0
. O 0

He O 0
required O 0
inotropic O 0
support O 0
and O 0
temporary O 0
pacing O 0
over O 0
the O 0
next O 0
48 O 0
hours O 0
. O 0

This O 0
case O 0
suggests O 0
there O 0
is O 0
a O 0
role O 0
for O 0
aggressive O 0
high O 0
dose O 0
intravenous O 0
calcium B-Chemical 0
therapy O 0
in O 0
severe O 0
diltiazem B-Chemical 0
overdose B-Disease 0
, O 0
particularly O 0
with O 0
the O 0
onset O 0
of O 0
asystole B-Disease 0
. O 0

It O 0
should O 0
be O 0
considered O 0
early O 0
in O 0
cases O 0
of O 0
cardiac B-Disease 0
arrest I-Disease 0
after O 0
diltiazem B-Chemical 0
overdose B-Disease 0
. O 0

The O 0
case O 0
also O 0
highlights O 0
the O 0
problems O 0
with O 0
delayed O 0
toxicity B-Disease 0
when O 0
whole O 0
bowel O 0
irrigation O 0
is O 0
not O 0
administered O 0
. O 0

Low B-Chemical 0
- I-Chemical 0
molecular I-Chemical 0
- I-Chemical 0
weight I-Chemical 0
heparin I-Chemical 0
for O 0
the O 0
treatment O 0
of O 0
patients O 0
with O 0
mechanical O 0
heart O 0
valves O 0
. O 0

BACKGROUND O 0
: O 0
The O 0
interruption O 0
of O 0
oral O 0
anticoagulant O 0
( O 0
OAC O 0
) O 0
administration O 0
is O 0
sometimes O 0
indicated O 0
in O 0
patients O 0
with O 0
mechanical O 0
heart O 0
valves O 0
, O 0
mainly O 0
before O 0
noncardiac O 0
surgery O 0
, O 0
non O 0
- O 0
surgical O 0
interventions O 0
, O 0
and O 0
pregnancy O 0
. O 0

Unfractionated B-Chemical 0
heparin I-Chemical 0
( O 0
UH B-Chemical 0
) O 0
is O 0
currently O 0
the O 0
substitute O 0
for O 0
selected O 0
patients O 0
. O 0

Low B-Chemical 0
- I-Chemical 0
molecular I-Chemical 0
- I-Chemical 0
weight I-Chemical 0
heparin I-Chemical 0
( O 0
LMWH B-Chemical 0
) O 0
offers O 0
theoretical O 0
advantages O 0
over O 0
UH B-Chemical 0
, O 0
but O 0
is O 0
not O 0
currently O 0
considered O 0
in O 0
clinical O 0
guidelines O 0
as O 0
an O 0
alternative O 0
to O 0
UH B-Chemical 0
in O 0
patients O 0
with O 0
prosthetic O 0
valves O 0
. O 0

HYPOTHESIS 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
review O 0
the O 0
data O 0
accumulated O 0
so O 0
far O 0
on O 0
the O 0
use O 0
of O 0
LMWH B-Chemical 0
in O 0
this O 0
patient O 0
population O 0
and O 0
to O 0
discuss O 0
its O 0
applicability O 0
in O 0
common O 0
practice O 0
. O 0

METHODS O 0
: O 0
For O 0
this O 0
paper O 0
, O 0
the O 0
current O 0
medical O 0
literature O 0
on O 0
LMWH B-Chemical 0
in O 0
patients O 0
with O 0
mechanical O 0
heart O 0
valves O 0
was O 0
extensively O 0
reviewed O 0
. O 0

RESULTS O 0
: O 0
There O 0
were O 0
eight O 0
series O 0
and O 0
six O 0
case O 0
reports O 0
. O 0

None O 0
of O 0
the O 0
studies O 0
was O 0
randomized O 0
, O 0
and O 0
only O 0
one O 0
was O 0
prospective O 0
. O 0

Data O 0
to O 0
establish O 0
the O 0
thromboembolic B-Disease 0
risk O 0
were O 0
incomplete O 0
. O 0

After O 0
excluding O 0
case O 0
reports O 0
, O 0
the O 0
following O 0
groups O 0
were O 0
constructed O 0
: O 0
( O 0
a O 0
) O 0
short O 0
- O 0
term O 0
administration O 0
, O 0
after O 0
valve O 0
insertion O 0
( O 0
n O 0
= O 0
212 O 0
) O 0
; O 0
( O 0
b O 0
) O 0
short O 0
- O 0
term O 0
, O 0
perioperative O 0
( O 0
noncardiac O 0
) O 0
/ O 0
periprocedural O 0
( O 0
n O 0
= O 0
114 O 0
) O 0
; O 0
( O 0
c O 0
) O 0
long O 0
- O 0
term O 0
, O 0
due O 0
to O 0
intolerance O 0
to O 0
OAC O 0
( O 0
n O 0
= O 0
16 O 0
) O 0
; O 0
( O 0
d O 0
) O 0
long O 0
- O 0
term O 0
, O 0
in O 0
pregnancy O 0
( O 0
n O 0
= O 0
10 O 0
) O 0
. O 0

The O 0
incidence O 0
rate O 0
of O 0
thromboembolism B-Disease 0
was O 0
0 O 0
. O 0
9 O 0
% O 0
for O 0
all O 0
the O 0
studies O 0
and O 0
0 O 0
. O 0
5 O 0
, O 0
0 O 0
, O 0
20 O 0
, O 0
and O 0
0 O 0
% O 0
in O 0
groups O 0
a O 0
, O 0
b O 0
, O 0
c O 0
, O 0
and O 0
d O 0
, O 0
respectively O 0
; O 0
for O 0
hemorrhage B-Disease 0
, O 0
the O 0
overall O 0
rate O 0
was O 0
3 O 0
. O 0
4 O 0
% O 0
( O 0
3 O 0
. O 0
8 O 0
, O 0
2 O 0
. O 0
6 O 0
, O 0
10 O 0
, O 0
and O 0
0 O 0
% O 0
for O 0
the O 0
respective O 0
groups O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
patients O 0
with O 0
mechanical O 0
heart O 0
valves O 0
, O 0
short O 0
- O 0
term O 0
LMWH B-Chemical 0
therapy O 0
compares O 0
favorably O 0
with O 0
UH B-Chemical 0
. O 0

Data O 0
on O 0
mid O 0
- O 0
and O 0
long O 0
- O 0
term O 0
LMWH B-Chemical 0
administration O 0
in O 0
these O 0
patients O 0
are O 0
sparse O 0
. O 0

Further O 0
randomized O 0
studies O 0
are O 0
needed O 0
to O 0
confirm O 0
the O 0
safety O 0
and O 0
precise O 0
indications O 0
for O 0
the O 0
use O 0
of O 0
LMWH B-Chemical 0
in O 0
patients O 0
with O 0
mechanical O 0
heart O 0
valves O 0
. O 0

Cardiac B-Disease 0
arrest I-Disease 0
after O 0
intravenous O 0
metoclopramide B-Chemical 0
- O 0
a O 0
case O 0
of O 0
five O 0
repeated O 0
injections O 0
of O 0
metoclopramide B-Chemical 0
causing O 0
five O 0
episodes O 0
of O 0
cardiac B-Disease 0
arrest I-Disease 0
. O 0

We O 0
describe O 0
a O 0
patient O 0
where O 0
intravenous O 0
injection O 0
of O 0
metoclopramide B-Chemical 0
was O 0
immediately O 0
followed O 0
by O 0
asystole B-Disease 0
repeatedly O 0
. O 0

The O 0
patient O 0
received O 0
metoclopramide B-Chemical 0
10 O 0
mg O 0
i O 0
. O 0
v O 0
. O 0
five O 0
times O 0
during O 0
48 O 0
h O 0
. O 0

After O 0
interviewing O 0
the O 0
attending O 0
nurses O 0
and O 0
reviewing O 0
the O 0
written O 0
documentation O 0
, O 0
it O 0
is O 0
clear O 0
that O 0
every O 0
administration O 0
of O 0
metoclopramide B-Chemical 0
was O 0
immediately O 0
( O 0
within O 0
s O 0
) O 0
followed O 0
by O 0
asystole B-Disease 0
. O 0

The O 0
asystole B-Disease 0
lasted O 0
15 O 0
- O 0
30 O 0
s O 0
on O 0
four O 0
occasions O 0
, O 0
on O 0
one O 0
occasion O 0
it O 0
lasted O 0
2 O 0
min O 0
. O 0

The O 0
patient O 0
received O 0
atropine B-Chemical 0
0 O 0
. O 0
5 O 0
- O 0
1 O 0
mg O 0
and O 0
chest O 0
compressions O 0
, O 0
before O 0
sinus O 0
rhythm O 0
again O 0
took O 0
over O 0
. O 0

We O 0
interpret O 0
this O 0
as O 0
episodes O 0
of O 0
cardiac B-Disease 0
arrest I-Disease 0
caused O 0
by O 0
metoclopramide B-Chemical 0
. O 0

The O 0
rapid O 0
injection O 0
via O 0
the O 0
central O 0
venous O 0
route O 0
and O 0
the O 0
concomitant O 0
tapering O 0
of O 0
dopamine B-Chemical 0
infusion O 0
might O 0
have O 0
contributed O 0
in O 0
precipitating O 0
the O 0
adverse O 0
drug O 0
reaction O 0
. O 0

Immunohistochemical O 0
study O 0
on O 0
inducible O 0
type O 0
of O 0
nitric B-Chemical 0
oxide I-Chemical 0
( O 0
iNOS O 0
) O 0
, O 0
basic O 0
fibroblast O 0
growth O 0
factor O 0
( O 0
bFGF O 0
) O 0
and O 0
tumor B-Disease 0
growth O 0
factor O 0
- O 0
beta1 O 0
( O 0
TGF O 0
- O 0
beta1 O 0
) O 0
in O 0
arteritis B-Disease 0
induced O 0
in O 0
rats O 0
by O 0
fenoldopam B-Chemical 0
and O 0
theophylline B-Chemical 0
, O 0
vasodilators O 0
. O 0

Arteritis B-Disease 0
induced O 0
in O 0
rats O 0
by O 0
vasodilators O 0
, O 0
fenoldopam B-Chemical 0
and O 0
theophylline B-Chemical 0
, O 0
was O 0
examined O 0
immunohistochemically O 0
for O 0
expressions O 0
of O 0
inducible O 0
type O 0
of O 0
nitric B-Chemical 0
oxide I-Chemical 0
synthase O 0
( O 0
iNOS O 0
) O 0
, O 0
basic O 0
fibroblast O 0
growth O 0
factor O 0
( O 0
bFGF O 0
) O 0
and O 0
tumor B-Disease 0
growth O 0
factor O 0
- O 0
beta1 O 0
( O 0
TGF O 0
- O 0
beta1 O 0
) O 0
. O 0

Rats O 0
were O 0
administered O 0
fenoldopam B-Chemical 0
for O 0
24 O 0
hours O 0
by O 0
intravenous O 0
infusion O 0
with O 0
or O 0
without O 0
following O 0
repeated O 0
daily O 0
oral O 0
administrations O 0
of O 0
theophylline B-Chemical 0
. O 0

Irrespective O 0
of O 0
theophylline B-Chemical 0
administration O 0
, O 0
iNOS O 0
antigens O 0
were O 0
remarkably O 0
abundant O 0
in O 0
ED O 0
- O 0
1 O 0
- O 0
positive O 0
cells O 0
on O 0
day O 0
5 O 0
and O 0
8 O 0
post O 0
- O 0
fenoldopam B-Chemical 0
- O 0
infusion O 0
( O 0
DPI O 0
) O 0
; O 0
bFGF O 0
antigens O 0
were O 0
remarkably O 0
abundant O 0
in O 0
ED O 0
- O 0
1 O 0
- O 0
positive O 0
cells O 0
on O 0
1 O 0
and O 0
3 O 0
DPI O 0
; O 0
TGF O 0
- O 0
beta1 O 0
antigens O 0
were O 0
observed O 0
in O 0
ED O 0
- O 0
1 O 0
- O 0
positive O 0
cells O 0
on O 0
and O 0
after O 0
5 O 0
DPI O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
the O 0
peak O 0
expression O 0
of O 0
iNOS O 0
antigen O 0
was O 0
followed O 0
by O 0
that O 0
of O 0
bFGF O 0
antigen O 0
, O 0
and O 0
bFGF O 0
may O 0
have O 0
a O 0
suppressive O 0
effect O 0
on O 0
iNOS O 0
expression O 0
in O 0
these O 0
rat O 0
arteritis B-Disease 0
models O 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
TGF O 0
- O 0
beta1 O 0
was O 0
not O 0
considered O 0
to O 0
have O 0
a O 0
suppressive O 0
effect O 0
on O 0
iNOS O 0
expression O 0
in O 0
these O 0
models O 0
. O 0

The O 0
striatum O 0
as O 0
a O 0
target O 0
for O 0
anti O 0
- O 0
rigor O 0
effects O 0
of O 0
an O 0
antagonist O 0
of O 0
mGluR1 O 0
, O 0
but O 0
not O 0
an O 0
agonist O 0
of O 0
group O 0
II O 0
metabotropic O 0
glutamate B-Chemical 0
receptors 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
find O 0
out O 0
whether O 0
the O 0
metabotropic O 0
receptor O 0
1 O 0
( O 0
mGluR1 O 0
) O 0
and O 0
group O 0
II O 0
mGluRs O 0
, O 0
localized O 0
in O 0
the O 0
striatum O 0
, O 0
are O 0
involved O 0
in O 0
antiparkinsonian O 0
- O 0
like O 0
effects O 0
in O 0
rats O 0
. O 0

Haloperidol B-Chemical 0
( O 0
1 O 0
mg O 0
/ O 0
kg O 0
ip O 0
) O 0
induced O 0
parkinsonian B-Disease 0
- O 0
like O 0
muscle B-Disease 0
rigidity I-Disease 0
, O 0
measured O 0
as O 0
an O 0
increased O 0
resistance O 0
of O 0
a O 0
rat O 0
' O 0
s O 0
hind O 0
foot O 0
to O 0
passive O 0
flexion O 0
and O 0
extension O 0
at O 0
the O 0
ankle O 0
joint O 0
. O 0

( B-Chemical 0
RS I-Chemical 0
) I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
aminoindan I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
5 I-Chemical 0
- I-Chemical 0
dicarboxylic I-Chemical 0
acid I-Chemical 0
( O 0
AIDA B-Chemical 0
; O 0
0 O 0
. O 0
5 O 0
- O 0
15 O 0
microg O 0
/ O 0
0 O 0
. O 0
5 O 0
microl O 0
) O 0
, O 0
a O 0
potent O 0
and O 0
selective O 0
mGluR1 O 0
antagonist O 0
, O 0
or O 0
( B-Chemical 0
2R I-Chemical 0
, I-Chemical 0
4R I-Chemical 0
) I-Chemical 0
- I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
aminopyrrolidine I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
dicarboxylate I-Chemical 0
( O 0
2R B-Chemical 0
, I-Chemical 0
4R I-Chemical 0
- I-Chemical 0
APDC I-Chemical 0
; O 0
7 O 0
. O 0
5 O 0
- O 0
15 O 0
microg O 0
/ O 0
0 O 0
. O 0
5 O 0
microl O 0
) O 0
, O 0
a O 0
selective O 0
group O 0
II O 0
agonist O 0
, O 0
was O 0
injected O 0
bilaterally O 0
into O 0
the O 0
striatum O 0
of O 0
haloperidol B-Chemical 0
- O 0
treated O 0
animals O 0
. O 0

AIDA B-Chemical 0
in O 0
doses O 0
of O 0
7 O 0
. O 0
5 O 0
- O 0
15 O 0
microg O 0
/ O 0
0 O 0
. O 0
5 O 0
microl O 0
diminished O 0
the O 0
haloperidol B-Chemical 0
- O 0
induced O 0
muscle B-Disease 0
rigidity I-Disease 0
. O 0

In O 0
contrast O 0
, O 0
2R B-Chemical 0
, I-Chemical 0
4R I-Chemical 0
- I-Chemical 0
APDC I-Chemical 0
injections O 0
were O 0
ineffective O 0
. O 0

The O 0
present O 0
results O 0
may O 0
suggest O 0
that O 0
the O 0
blockade O 0
of O 0
striatal O 0
mGluR1 O 0
, O 0
but O 0
not O 0
the O 0
stimulation O 0
of O 0
group O 0
II O 0
mGluRs O 0
, O 0
may O 0
ameliorate O 0
parkinsonian B-Disease 0
muscle B-Disease 0
rigidity I-Disease 0
. O 0

A O 0
phase O 0
II O 0
study O 0
of O 0
thalidomide B-Chemical 0
in O 0
advanced O 0
metastatic O 0
renal B-Disease 0
cell I-Disease 0
carcinoma I-Disease 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
evaluate O 0
the O 0
toxicity B-Disease 0
and O 0
activity O 0
of O 0
thalidomide B-Chemical 0
in O 0
patients O 0
with O 0
advanced O 0
metastatic O 0
renal B-Disease 0
cell I-Disease 0
cancer I-Disease 0
and O 0
to O 0
measure O 0
changes O 0
of O 0
one O 0
angiogenic O 0
factor O 0
, O 0
vascular O 0
endothelial O 0
growth O 0
factor O 0
( O 0
VEGF O 0
) O 0
165 O 0
, O 0
with O 0
therapy O 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
29 O 0
patients O 0
were O 0
enrolled O 0
on O 0
a O 0
study O 0
of O 0
thalidomide B-Chemical 0
using O 0
an O 0
intra O 0
- O 0
patient O 0
dose O 0
escalation O 0
schedule O 0
. O 0

Patients O 0
began O 0
thalidomide B-Chemical 0
at O 0
400 O 0
mg O 0
/ O 0
d O 0
and O 0
escalated O 0
as O 0
tolerated O 0
to O 0
1200 O 0
mg O 0
/ O 0
d O 0
by O 0
day O 0
54 O 0
. O 0

Fifty O 0
- O 0
nine O 0
per O 0
cent O 0
of O 0
patients O 0
had O 0
had O 0
previous O 0
therapy O 0
with O 0
IL O 0
- O 0
2 O 0
and O 0
52 O 0
% O 0
were O 0
performance O 0
status O 0
2 O 0
or O 0
3 O 0
. O 0

Systemic O 0
plasma O 0
VEGF165 O 0
levels O 0
were O 0
measured O 0
by O 0
dual O 0
monoclonal O 0
ELISA O 0
in O 0
8 O 0
patients O 0
. O 0

RESULTS O 0
: O 0
24 O 0
patients O 0
were O 0
evaluable O 0
for O 0
response O 0
with O 0
one O 0
partial O 0
response O 0
of O 0
11 O 0
months O 0
duration O 0
of O 0
a O 0
patient O 0
with O 0
hepatic O 0
and O 0
pulmonary O 0
metastases B-Disease 0
( O 0
4 O 0
% O 0
) O 0
, O 0
one O 0
minor O 0
response O 0
, O 0
and O 0
2 O 0
patients O 0
stable O 0
for O 0
over O 0
6 O 0
months O 0
. O 0

Somnolence B-Disease 0
and O 0
constipation B-Disease 0
were O 0
prominent O 0
toxicities B-Disease 0
and O 0
most O 0
patients O 0
could O 0
not O 0
tolerate O 0
the O 0
1200 O 0
mg O 0
/ O 0
day O 0
dose O 0
level O 0
. O 0

Systemic O 0
plasma O 0
VEGF165 O 0
levels O 0
did O 0
not O 0
change O 0
with O 0
therapy O 0
. O 0

CONCLUSION O 0
: O 0
These O 0
results O 0
are O 0
consistent O 0
with O 0
a O 0
low O 0
level O 0
of O 0
activity O 0
of O 0
thalidomide B-Chemical 0
in O 0
renal B-Disease 0
cell I-Disease 0
carcinoma I-Disease 0
. O 0

Administration O 0
of O 0
doses O 0
over O 0
800 O 0
mg O 0
/ O 0
day O 0
was O 0
difficult O 0
to O 0
achieve O 0
in O 0
this O 0
patient O 0
population O 0
, O 0
however O 0
lower O 0
doses O 0
were O 0
practical O 0
. O 0

The O 0
dose O 0
- O 0
response O 0
relationship O 0
, O 0
if O 0
any O 0
, O 0
of O 0
thalidomide B-Chemical 0
for O 0
renal B-Disease 0
cell I-Disease 0
carcinoma I-Disease 0
is O 0
unclear O 0
. O 0

Can O 0
lidocaine B-Chemical 0
reduce O 0
succinylcholine B-Chemical 0
induced O 0
postoperative B-Disease 0
myalgia I-Disease 0
? O 0

This O 0
study O 0
was O 0
undertaken O 0
to O 0
determine O 0
the O 0
effect O 0
of O 0
lidocaine B-Chemical 0
pretreatment O 0
on O 0
reduction O 0
of O 0
succinylcholine B-Chemical 0
- O 0
induced O 0
myalgia B-Disease 0
in O 0
patients O 0
undergoing O 0
general O 0
anesthesia O 0
for O 0
gynecological O 0
surgery O 0
. O 0

One O 0
hundred O 0
and O 0
thirty O 0
- O 0
five O 0
patients O 0
were O 0
assigned O 0
to O 0
one O 0
of O 0
three O 0
groups O 0
in O 0
a O 0
prospective O 0
, O 0
double O 0
blind O 0
, O 0
randomized O 0
manner O 0
. O 0

Group O 0
PS O 0
, O 0
the O 0
control O 0
group O 0
, O 0
received O 0
normal O 0
saline O 0
and O 0
succinylcholine B-Chemical 0
1 O 0
. O 0
5 O 0
mg O 0
x O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
; O 0
Group O 0
LS O 0
, O 0
lidocaine B-Chemical 0
1 O 0
. O 0
5 O 0
mg O 0
x O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
and O 0
succinylcholine B-Chemical 0
1 O 0
. O 0
5 O 0
mg O 0
x O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
; O 0
Group O 0
PR O 0
, O 0
normal O 0
saline O 0
and O 0
rocuronium B-Chemical 0
0 O 0
. O 0
6 O 0
mg O 0
x O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
. O 0

Morphine B-Chemical 0
0 O 0
. O 0
1 O 0
mg O 0
x O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
iv O 0
was O 0
given O 0
for O 0
premedication O 0
and O 0
all O 0
patients O 0
were O 0
monitored O 0
with O 0
a O 0
noninvasive O 0
blood O 0
pressure O 0
monitor O 0
, O 0
ECG O 0
and O 0
pulse O 0
oximetry O 0
. O 0

Anesthesia O 0
was O 0
induced O 0
with O 0
5 O 0
mg O 0
. O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
thiopental B-Chemical 0
iv O 0
. O 0
followed O 0
by O 0
succinylcholine B-Chemical 0
( O 0
Group O 0
PS O 0
, O 0
LS O 0
) O 0
or O 0
rocuronium B-Chemical 0
( O 0
Group O 0
PR O 0
) O 0
for O 0
tracheal O 0
intubation O 0
. O 0

Following O 0
administration O 0
of O 0
these O 0
agents O 0
, O 0
the O 0
presence O 0
, O 0
and O 0
degree O 0
of O 0
fasciculation B-Disease 0
were O 0
assessed O 0
visually O 0
on O 0
a O 0
four O 0
point O 0
scale O 0
by O 0
one O 0
investigator O 0
who O 0
was O 0
blinded O 0
to O 0
the O 0
drug O 0
administered O 0
. O 0

The O 0
blood O 0
pressure O 0
and O 0
heart O 0
rate O 0
of O 0
each O 0
patient O 0
were O 0
monitored O 0
on O 0
nine O 0
occasions O 0
. O 0

Twenty O 0
- O 0
four O 0
hours O 0
later O 0
, O 0
any O 0
myalgia B-Disease 0
experienced O 0
was O 0
assessed O 0
according O 0
to O 0
a O 0
structured O 0
questionaire O 0
and O 0
graded O 0
by O 0
a O 0
four O 0
point O 0
scale O 0
by O 0
one O 0
investigator O 0
blinded O 0
to O 0
the O 0
intraoperative O 0
management O 0
. O 0

The O 0
results O 0
indicate O 0
that O 0
muscle B-Disease 0
fasciculation I-Disease 0
was O 0
not O 0
found O 0
in O 0
Group O 0
PR O 0
while O 0
the O 0
patients O 0
in O 0
Group O 0
LS O 0
had O 0
a O 0
lower O 0
incidence O 0
of O 0
muscle B-Disease 0
fasciculation I-Disease 0
than O 0
those O 0
in O 0
Group O 0
PS O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

At O 0
24 O 0
h O 0
, O 0
the O 0
incidence O 0
of O 0
myalgia B-Disease 0
was O 0
higher O 0
in O 0
Group O 0
PS O 0
than O 0
in O 0
Group O 0
LS O 0
and O 0
PR O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

A O 0
correlation O 0
was O 0
not O 0
found O 0
between O 0
the O 0
incidence O 0
of O 0
myalgia B-Disease 0
and O 0
the O 0
occurrence O 0
of O 0
muscle B-Disease 0
fasciculation I-Disease 0
. O 0

The O 0
changes O 0
in O 0
systolic O 0
and O 0
diastolic O 0
blood O 0
pressure O 0
and O 0
heart O 0
rate O 0
were O 0
not O 0
significant O 0
among O 0
the O 0
three O 0
groups O 0
. O 0

In O 0
conclusion O 0
, O 0
where O 0
succinylcholine B-Chemical 0
is O 0
used O 0
, O 0
lidocaine B-Chemical 0
is O 0
proven O 0
to O 0
be O 0
the O 0
useful O 0
pretreatment O 0
agent O 0
for O 0
the O 0
reduction O 0
of O 0
postoperative B-Disease 0
myalgia I-Disease 0
. O 0

Reduced O 0
sodium B-Chemical 0
channel O 0
density O 0
, O 0
altered O 0
voltage O 0
dependence O 0
of O 0
inactivation O 0
, O 0
and O 0
increased O 0
susceptibility O 0
to O 0
seizures B-Disease 0
in O 0
mice O 0
lacking O 0
sodium B-Chemical 0
channel O 0
beta O 0
2 O 0
- O 0
subunits O 0
. O 0

Sodium B-Chemical 0
channel O 0
beta O 0
- O 0
subunits O 0
modulate O 0
channel O 0
gating O 0
, O 0
assembly O 0
, O 0
and O 0
cell O 0
surface O 0
expression O 0
in O 0
heterologous O 0
cell O 0
systems O 0
. O 0

We O 0
generated O 0
beta2 O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
to O 0
investigate O 0
the O 0
role O 0
of O 0
beta2 O 0
in O 0
control O 0
of O 0
sodium B-Chemical 0
channel O 0
density O 0
, O 0
localization O 0
, O 0
and O 0
function O 0
in O 0
neurons O 0
in O 0
vivo O 0
. O 0

Measurements O 0
of O 0
[ O 0
( O 0
3 O 0
) O 0
H O 0
] O 0
saxitoxin B-Chemical 0
( O 0
STX B-Chemical 0
) O 0
binding O 0
showed O 0
a O 0
significant O 0
reduction O 0
in O 0
the O 0
level O 0
of O 0
plasma O 0
membrane O 0
sodium B-Chemical 0
channels O 0
in O 0
beta2 O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
neurons O 0
. O 0

The O 0
loss O 0
of O 0
beta2 O 0
resulted O 0
in O 0
negative O 0
shifts O 0
in O 0
the O 0
voltage O 0
dependence O 0
of O 0
inactivation O 0
as O 0
well O 0
as O 0
significant O 0
decreases O 0
in O 0
sodium B-Chemical 0
current O 0
density O 0
in O 0
acutely O 0
dissociated O 0
hippocampal O 0
neurons O 0
. O 0

The O 0
integral O 0
of O 0
the O 0
compound O 0
action O 0
potential O 0
in O 0
optic O 0
nerve O 0
was O 0
significantly O 0
reduced O 0
, O 0
and O 0
the O 0
threshold O 0
for O 0
action O 0
potential O 0
generation O 0
was O 0
increased O 0
, O 0
indicating O 0
a O 0
reduction O 0
in O 0
the O 0
level O 0
of O 0
functional O 0
plasma O 0
membrane O 0
sodium B-Chemical 0
channels O 0
. O 0

In O 0
contrast O 0
, O 0
the O 0
conduction O 0
velocity O 0
, O 0
the O 0
number O 0
and O 0
size O 0
of O 0
axons O 0
in O 0
the O 0
optic O 0
nerve O 0
, O 0
and O 0
the O 0
specific O 0
localization O 0
of O 0
Na B-Chemical 0
( O 0
v O 0
) O 0
1 O 0
. O 0
6 O 0
channels O 0
in O 0
the O 0
nodes O 0
of O 0
Ranvier O 0
were O 0
unchanged O 0
. O 0

beta2 O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
displayed O 0
increased O 0
susceptibility O 0
to O 0
seizures B-Disease 0
, O 0
as O 0
indicated O 0
by O 0
reduced O 0
latency O 0
and O 0
threshold O 0
for O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
, O 0
but O 0
seemed O 0
normal O 0
in O 0
other O 0
neurological O 0
tests O 0
. O 0

Our O 0
observations O 0
show O 0
that O 0
beta2 O 0
- O 0
subunits O 0
play O 0
an O 0
important O 0
role O 0
in O 0
the O 0
regulation O 0
of O 0
sodium B-Chemical 0
channel O 0
density O 0
and O 0
function O 0
in O 0
neurons O 0
in O 0
vivo O 0
and O 0
are O 0
required O 0
for O 0
normal O 0
action O 0
potential O 0
generation O 0
and O 0
control O 0
of O 0
excitability O 0
. O 0

Acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
with O 0
concurrent O 0
bupropion B-Chemical 0
and O 0
carbimazole B-Chemical 0
therapy O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
report O 0
a O 0
case O 0
of O 0
fatal O 0
liver B-Disease 0
failure I-Disease 0
possibly O 0
associated O 0
with O 0
concurrent O 0
use O 0
of O 0
bupropion B-Chemical 0
and O 0
carbimazole B-Chemical 0
. O 0

CASE O 0
SUMMARY O 0
: O 0
A O 0
41 O 0
- O 0
year O 0
- O 0
old O 0
Chinese O 0
man O 0
with O 0
a O 0
history O 0
of O 0
hyperthyroidism B-Disease 0
had O 0
been O 0
treated O 0
with O 0
carbimazole B-Chemical 0
and O 0
propranolol B-Chemical 0
for O 0
the O 0
past O 0
5 O 0
years O 0
. O 0

He O 0
received O 0
a O 0
10 O 0
- O 0
day O 0
course O 0
of O 0
bupropion B-Chemical 0
as O 0
an O 0
aid O 0
for O 0
smoking O 0
cessation O 0
10 O 0
weeks O 0
prior O 0
to O 0
presentation O 0
. O 0

He O 0
developed O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
with O 0
rapid O 0
deterioration O 0
of O 0
renal O 0
function O 0
. O 0

Liver O 0
biopsy O 0
showed O 0
evidence O 0
of O 0
nonspecific 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
. O 0

His O 0
condition O 0
was O 0
further O 0
complicated O 0
by O 0
sepsis B-Disease 0
and O 0
coagulopathy B-Disease 0
. O 0

Death O 0
resulted O 0
19 O 0
days O 0
after O 0
the O 0
onset O 0
of O 0
symptoms O 0
. O 0

The O 0
likelihood O 0
that O 0
bupropion B-Chemical 0
induced O 0
hepatotoxicity B-Disease 0
in O 0
our O 0
patient O 0
was O 0
possible O 0
, O 0
based O 0
on O 0
the O 0
Naranjo O 0
probability O 0
scale O 0
. O 0

DISCUSSION O 0
: O 0
Although O 0
there O 0
is O 0
increasing O 0
evidence O 0
of O 0
hepatotoxicity B-Disease 0
induced O 0
by O 0
bupropion B-Chemical 0
, O 0
this O 0
is O 0
the O 0
first O 0
case O 0
of O 0
fatality O 0
that O 0
could O 0
have O 0
resulted O 0
from O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
in O 0
a O 0
patient O 0
receiving O 0
bupropion B-Chemical 0
while O 0
on O 0
concomitant O 0
treatment O 0
with O 0
carbimazole B-Chemical 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
possibility O 0
of O 0
acute B-Disease 0
liver I-Disease 0
insult I-Disease 0
induced O 0
by O 0
bupropion B-Chemical 0
given O 0
concurrently O 0
with O 0
other O 0
hepatotoxic B-Disease 0
drugs O 0
. O 0

Pyeloureteral O 0
filling O 0
defects O 0
associated O 0
with O 0
systemic O 0
anticoagulation O 0
: O 0
a O 0
case O 0
report O 0
. O 0

The O 0
etiology O 0
of O 0
pyeloureteritis B-Disease 0
cystica I-Disease 0
has O 0
long O 0
been O 0
attributed O 0
to O 0
chronic O 0
infection B-Disease 0
and O 0
inflammation B-Disease 0
. O 0

A O 0
case O 0
is O 0
presented O 0
that O 0
is O 0
unique O 0
in O 0
that O 0
the O 0
acute O 0
onset O 0
and O 0
the O 0
rapid O 0
resolution O 0
of O 0
pyeloureteral O 0
filling O 0
defects O 0
in O 0
this O 0
patient O 0
were O 0
documented O 0
by O 0
radiography O 0
. O 0

There O 0
is O 0
no O 0
evidence O 0
of O 0
antecedent O 0
or O 0
concurrent O 0
infection B-Disease 0
in O 0
this O 0
patient O 0
. O 0

The O 0
disease O 0
occurred O 0
subsequent O 0
to O 0
the O 0
initiation O 0
of O 0
heparin B-Chemical 0
therapy O 0
for O 0
suspected O 0
pelvic O 0
thrombophlebitis B-Disease 0
and O 0
cleared O 0
rapidly O 0
subsequent O 0
to O 0
its O 0
discontinuation O 0
. O 0

The O 0
rate O 0
of O 0
resolution O 0
of O 0
the O 0
radiographic O 0
findings O 0
may O 0
be O 0
helpful O 0
in O 0
distinguishing O 0
between O 0
true O 0
pyeloureteritis B-Disease 0
cystica I-Disease 0
and O 0
submucosal B-Disease 0
hemorrhage I-Disease 0
. O 0

Nephrotoxic B-Disease 0
effects O 0
in O 0
high O 0
- O 0
risk O 0
patients O 0
undergoing O 0
angiography O 0
. O 0

BACKGROUND O 0
: O 0
The O 0
use O 0
of O 0
iodinated O 0
contrast O 0
medium O 0
can O 0
result O 0
in O 0
nephropathy B-Disease 0
. O 0

Whether O 0
iso O 0
- O 0
osmolar O 0
contrast O 0
medium O 0
is O 0
less O 0
nephrotoxic B-Disease 0
than O 0
low O 0
- O 0
osmolar O 0
contrast O 0
medium O 0
in O 0
high O 0
- O 0
risk O 0
patients O 0
is O 0
uncertain O 0
. O 0

METHODS O 0
: O 0
We O 0
conducted O 0
a O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
prospective O 0
, O 0
multicenter O 0
study O 0
comparing O 0
the O 0
nephrotoxic B-Disease 0
effects O 0
of O 0
an O 0
iso O 0
- O 0
osmolar O 0
, O 0
dimeric O 0
, O 0
nonionic O 0
contrast O 0
medium O 0
, O 0
iodixanol B-Chemical 0
, O 0
with O 0
those O 0
of O 0
a O 0
low O 0
- O 0
osmolar O 0
, O 0
nonionic O 0
, O 0
monomeric O 0
contrast O 0
medium O 0
, O 0
iohexol B-Chemical 0
. O 0

The O 0
study O 0
involved O 0
129 O 0
patients O 0
with O 0
diabetes B-Disease 0
with O 0
serum O 0
creatinine B-Chemical 0
concentrations O 0
of O 0
1 O 0
. O 0
5 O 0
to O 0
3 O 0
. O 0
5 O 0
mg O 0
per O 0
deciliter O 0
who O 0
underwent O 0
coronary O 0
or O 0
aortofemoral O 0
angiography O 0
. O 0

The O 0
primary O 0
end O 0
point O 0
was O 0
the O 0
peak O 0
increase O 0
from O 0
base O 0
line O 0
in O 0
the O 0
creatinine B-Chemical 0
concentration O 0
during O 0
the O 0
three O 0
days O 0
after O 0
angiography O 0
. O 0

Other O 0
end O 0
points O 0
were O 0
an O 0
increase O 0
in O 0
the O 0
creatinine B-Chemical 0
concentration O 0
of O 0
0 O 0
. O 0
5 O 0
mg O 0
per O 0
deciliter O 0
or O 0
more O 0
, O 0
an O 0
increase O 0
of O 0
1 O 0
. O 0
0 O 0
mg O 0
per O 0
deciliter O 0
or O 0
more O 0
, O 0
and O 0
a O 0
change O 0
in O 0
the O 0
creatinine B-Chemical 0
concentration O 0
from O 0
day O 0
0 O 0
to O 0
day O 0
7 O 0
. O 0

RESULTS O 0
: O 0
The O 0
creatinine B-Chemical 0
concentration O 0
increased O 0
significantly O 0
less O 0
in O 0
patients O 0
who O 0
received O 0
iodixanol B-Chemical 0
. O 0

From O 0
day O 0
0 O 0
to O 0
day O 0
3 O 0
, O 0
the O 0
mean O 0
peak O 0
increase O 0
in O 0
creatinine B-Chemical 0
was O 0
0 O 0
. O 0
13 O 0
mg O 0
per O 0
deciliter O 0
in O 0
the O 0
iodixanol B-Chemical 0
group O 0
and O 0
0 O 0
. O 0
55 O 0
mg O 0
per O 0
deciliter O 0
in O 0
the O 0
iohexol B-Chemical 0
group O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
001 O 0
; O 0
the O 0
increase O 0
with O 0
iodixanol B-Chemical 0
minus O 0
the O 0
increase O 0
with O 0
iohexol B-Chemical 0
, O 0
- O 0
0 O 0
. O 0
42 O 0
mg O 0
per O 0
deciliter O 0
[ O 0
95 O 0
percent O 0
confidence O 0
interval O 0
, O 0
- O 0
0 O 0
. O 0
73 O 0
to O 0
- O 0
0 O 0
. O 0
22 O 0
] O 0
) O 0
. O 0

Two O 0
of O 0
the O 0
64 O 0
patients O 0
in O 0
the O 0
iodixanol B-Chemical 0
group O 0
( O 0
3 O 0
percent O 0
) O 0
had O 0
an O 0
increase O 0
in O 0
the O 0
creatinine B-Chemical 0
concentration O 0
of O 0
0 O 0
. O 0
5 O 0
mg O 0
per O 0
deciliter O 0
or O 0
more O 0
, O 0
as O 0
compared O 0
with O 0
17 O 0
of O 0
the O 0
65 O 0
patients O 0
in O 0
the O 0
iohexol B-Chemical 0
group O 0
( O 0
26 O 0
percent O 0
) O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
002 O 0
; O 0
odds O 0
ratio O 0
for O 0
such O 0
an O 0
increase O 0
in O 0
the O 0
iodixanol B-Chemical 0
group O 0
, O 0
0 O 0
. O 0
09 O 0
[ O 0
95 O 0
percent O 0
confidence O 0
interval O 0
, O 0
0 O 0
. O 0
02 O 0
to O 0
0 O 0
. O 0
41 O 0
] O 0
) O 0
. O 0

No O 0
patient O 0
receiving O 0
iodixanol B-Chemical 0
had O 0
an O 0
increase O 0
of O 0
1 O 0
. O 0
0 O 0
mg O 0
per O 0
deciliter O 0
or O 0
more O 0
, O 0
but O 0
10 O 0
patients O 0
in O 0
the O 0
iohexol B-Chemical 0
group O 0
( O 0
15 O 0
percent O 0
) O 0
did O 0
. O 0

The O 0
mean O 0
change O 0
in O 0
the O 0
creatinine B-Chemical 0
concentration O 0
from O 0
day O 0
0 O 0
to O 0
day O 0
7 O 0
was O 0
0 O 0
. O 0
07 O 0
mg O 0
per O 0
deciliter O 0
in O 0
the O 0
iodixanol B-Chemical 0
group O 0
and O 0
0 O 0
. O 0
24 O 0
mg O 0
per O 0
deciliter O 0
in O 0
the O 0
iohexol B-Chemical 0
group O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
003 O 0
; O 0
value O 0
in O 0
the O 0
iodixanol B-Chemical 0
group O 0
minus O 0
the O 0
value O 0
in O 0
the O 0
iohexol B-Chemical 0
group O 0
, O 0
- O 0
0 O 0
. O 0
17 O 0
mg O 0
per O 0
deciliter O 0
[ O 0
95 O 0
percent O 0
confidence O 0
interval O 0
, O 0
- O 0
0 O 0
. O 0
34 O 0
to O 0
- O 0
0 O 0
. O 0
07 O 0
] O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Nephropathy B-Disease 0
induced O 0
by O 0
contrast O 0
medium O 0
may O 0
be O 0
less O 0
likely O 0
to O 0
develop O 0
in O 0
high O 0
- O 0
risk O 0
patients O 0
when O 0
iodixanol B-Chemical 0
is O 0
used O 0
rather O 0
than O 0
a O 0
low O 0
- O 0
osmolar O 0
, O 0
nonionic O 0
contrast O 0
medium O 0
. O 0

Protective O 0
effect O 0
of O 0
edaravone B-Chemical 0
against O 0
streptomycin B-Chemical 0
- O 0
induced O 0
vestibulotoxicity B-Disease 0
in O 0
the O 0
guinea O 0
pig O 0
. O 0

This O 0
study O 0
investigated O 0
alleviation O 0
of O 0
streptomycin B-Chemical 0
- O 0
induced O 0
vestibulotoxicity B-Disease 0
by O 0
edaravone B-Chemical 0
in O 0
guinea O 0
pigs O 0
. O 0

Edaravone B-Chemical 0
, O 0
a O 0
free O 0
radical O 0
scavenger O 0
, O 0
has O 0
potent O 0
free O 0
radical O 0
quenching O 0
action O 0
and O 0
is O 0
used O 0
in O 0
clinical O 0
practice O 0
to O 0
treat O 0
cerebral B-Disease 0
infarction I-Disease 0
. O 0

Streptomycin B-Chemical 0
was O 0
administered O 0
to O 0
the O 0
inner O 0
ear O 0
by O 0
osmotic O 0
pump O 0
for O 0
24 O 0
h O 0
, O 0
and O 0
edaravone B-Chemical 0
( O 0
n O 0
= O 0
8 O 0
) O 0
or O 0
saline O 0
( O 0
n O 0
= O 0
6 O 0
) O 0
was O 0
intraperitoneally O 0
injected O 0
once O 0
a O 0
day O 0
for O 0
7 O 0
days O 0
. O 0

We O 0
observed O 0
horizontal O 0
vestibulo O 0
- O 0
ocular O 0
reflex O 0
as O 0
a O 0
marker O 0
of O 0
postoperative O 0
vestibular O 0
function O 0
. O 0

Animals O 0
injected O 0
with O 0
saline O 0
showed O 0
statistically O 0
smaller O 0
gains O 0
than O 0
those O 0
injected O 0
with O 0
edaravone B-Chemical 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
edaravone B-Chemical 0
suppresses O 0
streptomycin B-Chemical 0
- O 0
induced O 0
vestibulotoxicity B-Disease 0
. O 0

Levodopa B-Chemical 0
- O 0
induced O 0
oromandibular O 0
dystonia B-Disease 0
in O 0
progressive B-Disease 0
supranuclear I-Disease 0
palsy I-Disease 0
. O 0

Levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
have O 0
been O 0
reported O 0
in O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
and O 0
multiple B-Disease 0
system I-Disease 0
atrophy I-Disease 0
. O 0

Cranial O 0
dystonias B-Disease 0
are O 0
rare O 0
in O 0
patients O 0
with O 0
progressive B-Disease 0
supranuclear I-Disease 0
palsy I-Disease 0
( O 0
PSP B-Disease 0
) O 0
. O 0

In O 0
this O 0
report O 0
we O 0
describe O 0
an O 0
unusual O 0
case O 0
of O 0
reversible O 0
levodopa B-Chemical 0
- O 0
induced O 0
Oromandibular B-Disease 0
dystonia I-Disease 0
( O 0
OMD B-Disease 0
) O 0
in O 0
a O 0
PSP B-Disease 0
patient O 0
to O 0
highlight O 0
the O 0
importance O 0
of O 0
recognizing O 0
this O 0
drug O 0
related O 0
complication O 0
in O 0
the O 0
management O 0
of O 0
PSP B-Disease 0
, O 0
and O 0
discuss O 0
the O 0
possible O 0
underlying O 0
pathophysiology O 0
. O 0

Case O 0
report O 0
: O 0
Dexatrim B-Chemical 0
( O 0
Phenylpropanolamine B-Chemical 0
) O 0
as O 0
a O 0
cause O 0
of O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

Phenylpropanolamine B-Chemical 0
( O 0
PPA B-Chemical 0
) O 0
is O 0
a O 0
sympathetic O 0
amine B-Chemical 0
used O 0
in O 0
over O 0
- O 0
the O 0
- O 0
counter O 0
cold O 0
remedies O 0
and O 0
weight O 0
- O 0
control O 0
preparations O 0
worldwide O 0
. O 0

Its O 0
use O 0
has O 0
been O 0
associated O 0
with O 0
hypertensive B-Disease 0
episodes O 0
and O 0
hemorrhagic B-Disease 0
strokes I-Disease 0
in O 0
younger O 0
women O 0
. O 0

Several O 0
reports O 0
have O 0
linked O 0
the O 0
abuse O 0
of O 0
PPA B-Chemical 0
with O 0
myocardial B-Disease 0
injury I-Disease 0
, O 0
especially O 0
when O 0
overdose B-Disease 0
is O 0
involved O 0
. O 0

We O 0
report O 0
here O 0
the O 0
first O 0
case O 0
of O 0
Dexatrim B-Chemical 0
( O 0
PPA B-Chemical 0
) O 0
- O 0
induced O 0
myocardial B-Disease 0
injury I-Disease 0
in O 0
a O 0
young O 0
woman O 0
who O 0
was O 0
using O 0
it O 0
at O 0
recommended O 0
doses O 0
for O 0
weight O 0
control O 0
. O 0

In O 0
addition O 0
, O 0
we O 0
review O 0
the O 0
7 O 0
other O 0
cases O 0
of O 0
PPA B-Chemical 0
related O 0
myocardial B-Disease 0
injury I-Disease 0
that O 0
have O 0
been O 0
reported O 0
so O 0
far O 0
. O 0

Physicians O 0
and O 0
patients O 0
should O 0
be O 0
alert O 0
to O 0
the O 0
potential O 0
cardiac O 0
risk O 0
associated O 0
with O 0
the O 0
use O 0
of O 0
PPA B-Chemical 0
, O 0
even O 0
at O 0
doses O 0
generally O 0
considered O 0
to O 0
be O 0
safe O 0
. O 0

Differential O 0
diagnosis O 0
of O 0
high O 0
serum O 0
creatine B-Chemical 0
kinase O 0
levels O 0
in O 0
systemic B-Disease 0
lupus I-Disease 0
erythematosus I-Disease 0
. O 0

We O 0
report O 0
the O 0
clinical O 0
and O 0
bioptic O 0
findings O 0
for O 0
a O 0
57 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
severe O 0
chloroquine B-Chemical 0
- O 0
induced O 0
myopathy B-Disease 0
. O 0

Since O 0
1989 O 0
, O 0
she O 0
had O 0
been O 0
suffering O 0
from O 0
systemic B-Disease 0
lupus I-Disease 0
erythematosus I-Disease 0
( O 0
SLE B-Disease 0
) O 0
with O 0
renal B-Disease 0
involvement I-Disease 0
and O 0
undergone O 0
periods O 0
of O 0
treatment O 0
with O 0
azathioprine B-Chemical 0
and O 0
cyclophosphamide B-Chemical 0
. O 0

Additional O 0
therapy O 0
with O 0
chloroquine B-Chemical 0
( O 0
CQ B-Chemical 0
) O 0
was O 0
started O 0
because O 0
of O 0
arthralgia B-Disease 0
. O 0

At O 0
the O 0
same O 0
time O 0
, O 0
slightly O 0
increased O 0
creatine B-Chemical 0
kinase O 0
( O 0
CK O 0
) O 0
levels O 0
were O 0
noted O 0
. O 0

Myositis B-Disease 0
was O 0
suspected O 0
, O 0
and O 0
the O 0
patient O 0
was O 0
treated O 0
with O 0
steroids B-Chemical 0
. O 0

The O 0
CK O 0
increase O 0
persisted O 0
, O 0
however O 0
, O 0
and O 0
she O 0
developed O 0
progressive O 0
muscular B-Disease 0
weakness I-Disease 0
and O 0
muscular B-Disease 0
atrophy I-Disease 0
. O 0

Routine O 0
controls O 0
revealed O 0
markedly O 0
elevated O 0
CK O 0
levels O 0
of O 0
1 O 0
, O 0
700 O 0
U O 0
/ O 0
l O 0
. O 0

The O 0
neurological O 0
and O 0
electrophysiological O 0
findings O 0
were O 0
not O 0
typical O 0
of O 0
myositis B-Disease 0
. O 0

Thus O 0
, O 0
muscle O 0
biopsy O 0
of O 0
the O 0
deltoid O 0
muscle O 0
was O 0
performed O 0
in O 0
order O 0
to O 0
exclude O 0
polymyositis B-Disease 0
or O 0
toxic O 0
myopathy B-Disease 0
. O 0

As O 0
it O 0
revealed O 0
chloroquine B-Chemical 0
- O 0
induced O 0
myopathy B-Disease 0
, O 0
medication O 0
was O 0
stopped O 0
. O 0

Discriminating O 0
between O 0
primary O 0
SLE B-Disease 0
- O 0
induced O 0
affection B-Disease 0
of I-Disease 0
the I-Disease 0
musculoskeletal I-Disease 0
system I-Disease 0
and O 0
drug O 0
- O 0
induced O 0
side O 0
effects O 0
is O 0
important O 0
for O 0
appropriate O 0
treatment O 0
of O 0
SLE B-Disease 0
patients O 0
. O 0

Seizure B-Disease 0
associated O 0
with O 0
sleep B-Disease 0
deprivation I-Disease 0
and O 0
sustained O 0
- O 0
release O 0
bupropion B-Chemical 0
. O 0

This O 0
case O 0
report O 0
describes O 0
a O 0
generalized O 0
seizure B-Disease 0
associated O 0
with O 0
sustained O 0
- O 0
release O 0
bupropion B-Chemical 0
use O 0
and O 0
sleep B-Disease 0
deprivation I-Disease 0
. O 0

The O 0
subject O 0
, O 0
a O 0
31 O 0
- O 0
year O 0
- O 0
old O 0
female O 0
smoker O 0
, O 0
was O 0
participating O 0
in O 0
a O 0
clinical O 0
trial O 0
evaluating O 0
an O 0
investigational O 0
medication O 0
for O 0
smoking O 0
cessation O 0
that O 0
used O 0
sustained O 0
- O 0
release O 0
bupropion B-Chemical 0
as O 0
an O 0
active O 0
control O 0
. O 0

After O 0
5 O 0
weeks O 0
of O 0
bupropion B-Chemical 0
use O 0
, O 0
the O 0
subject O 0
experienced O 0
a O 0
generalized O 0
tonic O 0
clonic O 0
seizure B-Disease 0
after O 0
staying O 0
up O 0
nearly O 0
all O 0
night O 0
packing O 0
and O 0
moving O 0
to O 0
a O 0
new O 0
residence O 0
. O 0

The O 0
patient O 0
had O 0
no O 0
other O 0
risk O 0
factors O 0
for O 0
seizures B-Disease 0
. O 0

We O 0
suggest O 0
that O 0
sleep B-Disease 0
deprivation I-Disease 0
may O 0
add O 0
to O 0
the O 0
risk O 0
of O 0
bupropion B-Chemical 0
- O 0
associated O 0
seizures B-Disease 0
. O 0

Postoperative B-Disease 0
myalgia I-Disease 0
after O 0
succinylcholine B-Chemical 0
: O 0
no O 0
evidence O 0
for O 0
an O 0
inflammatory O 0
origin O 0
. O 0

A O 0
common O 0
side O 0
effect O 0
associated O 0
with O 0
succinylcholine B-Chemical 0
is O 0
postoperative B-Disease 0
myalgia I-Disease 0
. O 0

The O 0
pathogenesis O 0
of O 0
this O 0
myalgia B-Disease 0
is O 0
still O 0
unclear O 0
; O 0
inflammation B-Disease 0
has O 0
been O 0
suggested O 0
but O 0
without O 0
convincing O 0
evidence O 0
. O 0

We O 0
designed O 0
the O 0
present O 0
study O 0
to O 0
investigate O 0
whether O 0
an O 0
inflammatory O 0
reaction O 0
contributes O 0
to O 0
this O 0
myalgia B-Disease 0
. O 0

The O 0
incidence O 0
and O 0
severity O 0
of O 0
succinylcholine B-Chemical 0
- O 0
associated O 0
myalgia B-Disease 0
was O 0
determined O 0
in O 0
64 O 0
patients O 0
pretreated O 0
with O 0
saline O 0
or O 0
dexamethasone B-Chemical 0
before O 0
succinylcholine B-Chemical 0
( O 0
n O 0
= O 0
32 O 0
for O 0
each O 0
) O 0
. O 0

Incidence O 0
and O 0
severity O 0
of O 0
myalgia B-Disease 0
did O 0
not O 0
differ O 0
significantly O 0
between O 0
the O 0
two O 0
groups O 0
: O 0
15 O 0
patients O 0
in O 0
the O 0
dexamethasone B-Chemical 0
group O 0
complained O 0
of O 0
myalgia B-Disease 0
compared O 0
with O 0
18 O 0
patients O 0
in O 0
the O 0
saline O 0
group O 0
, O 0
and O 0
severe O 0
myalgia B-Disease 0
was O 0
reported O 0
by O 0
five O 0
patients O 0
and O 0
three O 0
patients O 0
, O 0
respectively O 0
( O 0
not O 0
significant O 0
) O 0
. O 0

At O 0
48 O 0
h O 0
after O 0
surgery O 0
, O 0
12 O 0
patients O 0
in O 0
both O 0
groups O 0
still O 0
suffered O 0
from O 0
myalgia B-Disease 0
( O 0
not O 0
significant O 0
) O 0
. O 0

In O 0
addition O 0
, O 0
interleukin O 0
- O 0
6 O 0
( O 0
IL O 0
- O 0
6 O 0
) O 0
as O 0
an O 0
early O 0
marker O 0
of O 0
inflammation B-Disease 0
was O 0
assessed O 0
in O 0
a O 0
subgroup O 0
of O 0
10 O 0
patients O 0
pretreated O 0
with O 0
saline O 0
. O 0

We O 0
found O 0
an O 0
increase O 0
of O 0
IL O 0
- O 0
6 O 0
for O 0
only O 0
three O 0
patients O 0
, O 0
but O 0
only O 0
one O 0
patient O 0
reported O 0
myalgia B-Disease 0
; O 0
no O 0
relationship O 0
between O 0
myalgia B-Disease 0
and O 0
the O 0
increase O 0
of O 0
IL O 0
- O 0
6 O 0
was O 0
found O 0
. O 0

In O 0
conclusion O 0
, O 0
there O 0
is O 0
no O 0
evidence O 0
for O 0
an O 0
inflammatory O 0
origin O 0
of O 0
succinylcholine B-Chemical 0
- O 0
associated O 0
myalgia B-Disease 0
. O 0

IMPLICATIONS O 0
: O 0
Administration O 0
of O 0
dexamethasone B-Chemical 0
before O 0
succinylcholine B-Chemical 0
was O 0
not O 0
effective O 0
in O 0
decreasing O 0
the O 0
incidence O 0
or O 0
the O 0
severity O 0
of O 0
succinylcholine B-Chemical 0
- O 0
induced O 0
postoperative B-Disease 0
myalgia I-Disease 0
. O 0

Furthermore O 0
, O 0
there O 0
was O 0
no O 0
significant O 0
relationship O 0
between O 0
postoperative B-Disease 0
myalgia I-Disease 0
and O 0
time O 0
course O 0
of O 0
interleukin O 0
- O 0
6 O 0
concentrations O 0
, O 0
a O 0
marker O 0
of O 0
inflammation B-Disease 0
. O 0

Pretreatment O 0
with O 0
dexamethasone B-Chemical 0
is O 0
not O 0
justified O 0
to O 0
prevent O 0
postoperative B-Disease 0
myalgia I-Disease 0
after O 0
succinylcholine B-Chemical 0
. O 0

Effect O 0
of O 0
lindane B-Chemical 0
on O 0
hepatic O 0
and O 0
brain O 0
cytochrome O 0
P450s O 0
and O 0
influence O 0
of O 0
P450 O 0
modulation O 0
in O 0
lindane B-Chemical 0
induced O 0
neurotoxicity B-Disease 0
. O 0

Oral O 0
administration O 0
of O 0
lindane B-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
, O 0
5 O 0
, O 0
10 O 0
and O 0
15 O 0
mg O 0
/ O 0
kg O 0
, O 0
body O 0
weight O 0
) O 0
for O 0
5 O 0
days O 0
was O 0
found O 0
to O 0
produce O 0
a O 0
dose O 0
- O 0
dependent O 0
increase O 0
in O 0
the O 0
activity O 0
of O 0
P450 O 0
dependent O 0
7 O 0
- O 0
ethoxyresorufin O 0
- O 0
O O 0
- O 0
deethylase O 0
( O 0
EROD O 0
) O 0
, O 0
7 O 0
- O 0
pentoxyresorufin O 0
- O 0
O O 0
- O 0
dealkylase O 0
( O 0
PROD O 0
) O 0
and O 0
N B-Chemical 0
- I-Chemical 0
nitrosodimethylamine I-Chemical 0
demethylase O 0
( O 0
NDMA B-Chemical 0
- O 0
d O 0
) O 0
in O 0
rat O 0
brain O 0
and O 0
liver O 0
. O 0

A O 0
significant O 0
increase O 0
in O 0
the O 0
hepatic O 0
and O 0
brain O 0
P450 O 0
monooxygenases O 0
was O 0
also O 0
observed O 0
when O 0
the O 0
duration O 0
of O 0
exposure O 0
of O 0
low O 0
dose O 0
( O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
of O 0
lindane B-Chemical 0
was O 0
increased O 0
from O 0
5 O 0
days O 0
to O 0
15 O 0
or O 0
21 O 0
days O 0
. O 0

As O 0
observed O 0
with O 0
different O 0
doses O 0
, O 0
the O 0
magnitude O 0
of O 0
induction O 0
in O 0
the O 0
activity O 0
of O 0
P450 O 0
monooxygenases O 0
was O 0
several O 0
fold O 0
higher O 0
in O 0
liver O 0
microsomes O 0
when O 0
compared O 0
with O 0
the O 0
brain O 0
. O 0

Western O 0
blotting O 0
studies O 0
have O 0
indicated O 0
that O 0
the O 0
increase O 0
in O 0
the O 0
P450 O 0
enzymes O 0
could O 0
be O 0
due O 0
to O 0
the O 0
increase O 0
in O 0
the O 0
expression O 0
of O 0
P450 O 0
1A1 O 0
/ O 0
1A2 O 0
, O 0
2B1 O 0
/ O 0
2B2 O 0
and O 0
2E1 O 0
isoenzymes O 0
. O 0

In O 0
vitro O 0
studies O 0
using O 0
organic O 0
inhibitors O 0
specific O 0
for O 0
individual O 0
P450 O 0
isoenzymes O 0
and O 0
antibody O 0
inhibition O 0
experiments O 0
have O 0
further O 0
demonstrated O 0
that O 0
the O 0
increase O 0
in O 0
the O 0
activity O 0
of O 0
PROD O 0
, O 0
EROD O 0
and O 0
NDMA B-Chemical 0
- O 0
d O 0
are O 0
due O 0
to O 0
the O 0
increase O 0
in O 0
the O 0
levels O 0
of O 0
P450 O 0
2B1 O 0
/ O 0
2B2 O 0
, O 0
1A1 O 0
/ O 0
1A2 O 0
and O 0
2E1 O 0
isoenzymes O 0
, O 0
respectively O 0
. O 0

Induction O 0
studies O 0
have O 0
further O 0
shown O 0
that O 0
while O 0
pretreatment O 0
of O 0
3 B-Chemical 0
- I-Chemical 0
methylcholanthrene I-Chemical 0
( O 0
MC B-Chemical 0
) O 0
, O 0
an O 0
inducer O 0
of O 0
P4501A1 O 0
/ O 0
1A2 O 0
, 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
incidence O 0
of O 0
lindane B-Chemical 0
induced O 0
convulsions B-Disease 0
, O 0
pretreatment O 0
with O 0
phenobarbital B-Chemical 0
( O 0
PB O 0
) O 0
, O 0
an O 0
inducer O 0
of O 0
P450 O 0
2B1 O 0
/ O 0
2B2 O 0
or O 0
ethanol B-Chemical 0
, O 0
an O 0
inducer O 0
of O 0
P450 O 0
2E1 O 0
catalysed O 0
reactions O 0
, O 0
significantly O 0
increased O 0
the O 0
incidence O 0
of O 0
lindane B-Chemical 0
induced O 0
convulsions B-Disease 0
. O 0

Similarly O 0
, O 0
when O 0
the O 0
P450 O 0
- O 0
mediated O 0
metabolism O 0
of O 0
lindane B-Chemical 0
was O 0
blocked O 0
by O 0
cobalt B-Chemical 0
chloride I-Chemical 0
incidence O 0
of O 0
convulsions B-Disease 0
was O 0
increased O 0
in O 0
animals O 0
treated O 0
with O 0
lindane B-Chemical 0
indicating O 0
that O 0
lindane B-Chemical 0
per O 0
se O 0
or O 0
its O 0
metabolites O 0
formed O 0
by O 0
PB O 0
or O 0
ethanol B-Chemical 0
inducible O 0
P450 O 0
isoenzymes O 0
are O 0
involved O 0
in O 0
its O 0
neurobehavioral O 0
toxicity B-Disease 0
. O 0

Absolute O 0
and O 0
attributable O 0
risk O 0
of O 0
venous B-Disease 0
thromboembolism I-Disease 0
in O 0
women O 0
on O 0
combined O 0
cyproterone B-Chemical 0
acetate I-Chemical 0
and O 0
ethinylestradiol B-Chemical 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
achieve O 0
absolute O 0
risk O 0
estimates O 0
of O 0
venous B-Disease 0
thromboembolism I-Disease 0
( O 0
VTE B-Disease 0
) O 0
among O 0
women O 0
on O 0
cyproterone B-Chemical 0
acetate I-Chemical 0
plus O 0
ethinylestradiol B-Chemical 0
( O 0
CPA B-Chemical 0
/ O 0
EE B-Chemical 0
) O 0
, O 0
and O 0
among O 0
women O 0
on O 0
combined B-Chemical 0
oral I-Chemical 0
contraceptives I-Chemical 0
( O 0
COCs B-Chemical 0
) O 0
. O 0

METHODS O 0
: O 0
From O 0
the O 0
Danish O 0
National O 0
Register O 0
of O 0
Patients O 0
( O 0
NRP O 0
) O 0
, O 0
1996 O 0
to O 0
1998 O 0
, O 0
the O 0
records O 0
of O 0
1 O 0
. O 0
1 O 0
million O 0
Danish O 0
women O 0
, O 0
ages O 0
15 O 0
to O 0
44 O 0
years O 0
, O 0
were O 0
searched O 0
for O 0
evidence O 0
of O 0
VTE B-Disease 0
. O 0

COC B-Chemical 0
use O 0
was O 0
ascertained O 0
through O 0
mailed O 0
questionnaires O 0
. O 0

Sales O 0
statistics O 0
of O 0
COCs B-Chemical 0
and O 0
CPA B-Chemical 0
/ O 0
EE B-Chemical 0
were O 0
provided O 0
through O 0
Danish O 0
Drug O 0
Statistics O 0
. O 0

RESULTS O 0
: O 0
During O 0
the O 0
time O 0
frame O 0
of O 0
the O 0
study O 0
, O 0
330 O 0
women O 0
were O 0
found O 0
to O 0
have O 0
had O 0
VTE B-Disease 0
while O 0
on O 0
COCs B-Chemical 0
. O 0

Of O 0
these O 0
women O 0
, O 0
67 O 0
were O 0
on O 0
levonorgestrel B-Chemical 0
- O 0
containing O 0
COCs B-Chemical 0
. O 0

Eleven O 0
were O 0
on O 0
CPA B-Chemical 0
/ O 0
EE B-Chemical 0
. O 0

The O 0
corresponding O 0
absolute O 0
risk O 0
of O 0
VTE B-Disease 0
was O 0
3 O 0
. O 0
4 O 0
( O 0
range O 0
, O 0
3 O 0
. O 0
1 O 0
- O 0
3 O 0
. O 0
8 O 0
) O 0
per O 0
10 O 0
000 O 0
women O 0
years O 0
among O 0
the O 0
women O 0
on O 0
COCs B-Chemical 0
, O 0
4 O 0
. O 0
2 O 0
( O 0
range O 0
, O 0
3 O 0
. O 0
2 O 0
- O 0
5 O 0
. O 0
2 O 0
) O 0
per O 0
10 O 0
000 O 0
women O 0
years O 0
among O 0
women O 0
on O 0
levonorgestrel B-Chemical 0
- O 0
containing O 0
COCs B-Chemical 0
, O 0
and O 0
3 O 0
. O 0
1 O 0
( O 0
range O 0
, O 0
1 O 0
. O 0
3 O 0
- O 0
4 O 0
. O 0
9 O 0
) O 0
per O 0
10 O 0
000 O 0
women O 0
years O 0
among O 0
the O 0
women O 0
on O 0
CPA B-Chemical 0
/ O 0
EE B-Chemical 0
. O 0

CONCLUSION O 0
: O 0
Our O 0
results O 0
suggest O 0
the O 0
absolute O 0
risk O 0
of O 0
VTE B-Disease 0
among O 0
Danish O 0
women O 0
on O 0
COCs B-Chemical 0
is O 0
similar O 0
to O 0
that O 0
among O 0
women O 0
taking O 0
CPA B-Chemical 0
/ O 0
EE B-Chemical 0
. O 0

Comparison O 0
of O 0
developmental O 0
toxicology O 0
of O 0
aspirin B-Chemical 0
( O 0
acetylsalicylic B-Chemical 0
acid I-Chemical 0
) O 0
in O 0
rats O 0
using O 0
selected O 0
dosing O 0
paradigms O 0
. O 0

BACKGROUND O 0
: O 0
Analysis O 0
of O 0
the O 0
literature O 0
for O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
drugs O 0
( O 0
NSAIDs O 0
) O 0
suggests O 0
that O 0
a O 0
low O 0
incidence O 0
of O 0
developmental B-Disease 0
anomalies I-Disease 0
occurs O 0
in O 0
rats O 0
given O 0
NSAIDs O 0
on O 0
specific O 0
days O 0
during O 0
organogenesis O 0
. O 0

Aspirin B-Chemical 0
( O 0
acetylsalicylic B-Chemical 0
acid I-Chemical 0
[ O 0
ASA B-Chemical 0
] O 0
) O 0
, O 0
an O 0
irreversible O 0
cyclooxygenase O 0
1 O 0
and O 0
2 O 0
inhibitor O 0
, O 0
induces O 0
developmental B-Disease 0
anomalies I-Disease 0
when O 0
administered O 0
to O 0
Wistar O 0
rats O 0
on O 0
gestational O 0
day O 0
( O 0
GD O 0
) O 0
9 O 0
, O 0
10 O 0
, O 0
or O 0
11 O 0
( O 0
Kimmel O 0
CA O 0
, O 0
Wilson O 0
JG O 0
, O 0
Schumacher O 0
HJ O 0
. O 0
Teratology O 0
4 O 0
: O 0
15 O 0
- O 0
24 O 0
, O 0
1971 O 0
) O 0
. O 0

There O 0
are O 0
no O 0
published O 0
ASA B-Chemical 0
studies O 0
using O 0
the O 0
multiple O 0
dosing O 0
paradigm O 0
of O 0
GDs O 0
6 O 0
to O 0
17 O 0
. O 0

Objectives O 0
of O 0
the O 0
current O 0
study O 0
were O 0
to O 0
compare O 0
results O 0
between O 0
Sprague O 0
- O 0
Dawley O 0
( O 0
SD O 0
) O 0
and O 0
Wistar O 0
strains O 0
when O 0
ASA B-Chemical 0
is O 0
administered O 0
on O 0
GD O 0
9 O 0
, O 0
10 O 0
, O 0
or O 0
11 O 0
; O 0
to O 0
compare O 0
the O 0
malformation O 0
patterns O 0
following O 0
single O 0
and O 0
multiple O 0
dosings O 0
during O 0
organogenesis O 0
in O 0
SD O 0
rats O 0
; O 0
and O 0
to O 0
test O 0
the O 0
hypothesis O 0
that O 0
maternal O 0
gastrointestinal B-Disease 0
toxicity I-Disease 0
confounds O 0
the O 0
detection O 0
of O 0
low O 0
incidence O 0
malformations B-Disease 0
with O 0
ASA B-Chemical 0
when O 0
a O 0
multiple O 0
dosing O 0
paradigm O 0
is O 0
used O 0
. O 0

METHODS O 0
: O 0
ASA B-Chemical 0
was O 0
administered O 0
as O 0
a O 0
single O 0
dose O 0
on O 0
GD O 0
9 O 0
( O 0
0 O 0
, O 0
250 O 0
, O 0
500 O 0
, O 0
or O 0
625 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
10 O 0
( O 0
0 O 0
, O 0
500 O 0
, O 0
625 O 0
, O 0
or O 0
750 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
or O 0
11 O 0
( O 0
0 O 0
, O 0
500 O 0
, O 0
750 O 0
, O 0
or O 0
1000 O 0
mg O 0
/ O 0
kg O 0
) O 0
and O 0
from O 0
GD O 0
6 O 0
to O 0
GD O 0
17 O 0
( O 0
0 O 0
, O 0
50 O 0
, O 0
125 O 0
, O 0
or O 0
250 O 0
mg O 0
/ O 0
kg O 0
a O 0
day O 0
) O 0
in O 0
the O 0
multiple O 0
dose O 0
study O 0
to O 0
SD O 0
rats O 0
. O 0

Animals O 0
were O 0
killed O 0
on O 0
GD O 0
21 O 0
, O 0
and O 0
fetuses O 0
were O 0
examined O 0
viscerally O 0
. O 0

RESULTS O 0
: O 0
The O 0
literature O 0
evaluation O 0
suggested O 0
that O 0
NSAIDs O 0
induce O 0
ventricular B-Disease 0
septal I-Disease 0
defects I-Disease 0
( O 0
VSDs B-Disease 0
) O 0
and O 0
midline B-Disease 0
defects I-Disease 0
( O 0
MDs B-Disease 0
) O 0
in O 0
rats O 0
and O 0
diaphragmatic B-Disease 0
hernia I-Disease 0
( O 0
DH B-Disease 0
) O 0
, O 0
MDs B-Disease 0
, O 0
and O 0
VSDs B-Disease 0
in O 0
rabbits O 0
( O 0
Cook O 0
JC O 0
et O 0
al O 0
. O 0
, O 0
2003 O 0
) O 0
; O 0
hence O 0
, O 0
the O 0
present O 0
study O 0
focused O 0
on O 0
these O 0
malformations B-Disease 0
, O 0
even O 0
though O 0
ASA B-Chemical 0
induces O 0
several O 0
other O 0
low O 0
- O 0
incidence O 0
malformations B-Disease 0
. O 0

In O 0
single O 0
dose O 0
studies O 0
, O 0
DH B-Disease 0
, O 0
MD B-Disease 0
, O 0
and O 0
VSD B-Disease 0
were O 0
induced O 0
on O 0
GDs O 0
9 O 0
and O 0
10 O 0
. O 0

VSD B-Disease 0
also O 0
was O 0
noted O 0
following O 0
treatment O 0
on O 0
GD O 0
11 O 0
. O 0

In O 0
contrast O 0
, O 0
DH B-Disease 0
and O 0
MD B-Disease 0
were O 0
noted O 0
in O 0
the O 0
multiple O 0
dose O 0
study O 0
design O 0
only O 0
in O 0
the O 0
high O 0
- O 0
dose O 0
group O 0
, O 0
and O 0
VSD B-Disease 0
was O 0
noted O 0
across O 0
all O 0
dose O 0
groups O 0
. O 0

CONCLUSIONS O 0
: O 0
High O 0
concordance O 0
in O 0
major O 0
developmental B-Disease 0
anomalies I-Disease 0
between O 0
Wistar O 0
and O 0
SD O 0
rats O 0
were O 0
noted O 0
with O 0
the O 0
exception O 0
of O 0
VSD B-Disease 0
in O 0
the O 0
SD O 0
rats O 0
and O 0
hydrocephalus B-Disease 0
in O 0
the O 0
Wistar O 0
rats O 0
. O 0

Variations O 0
and O 0
malformations B-Disease 0
were O 0
similar O 0
when O 0
ASA B-Chemical 0
was O 0
administered O 0
as O 0
a O 0
single O 0
dose O 0
or O 0
during O 0
the O 0
period O 0
of O 0
organogenesis O 0
( O 0
GDs O 0
6 O 0
to O 0
17 O 0
) O 0
. O 0

It O 0
was O 0
also O 0
evident O 0
that O 0
, O 0
by O 0
titrating O 0
the O 0
dose O 0
to O 0
achieve O 0
a O 0
maximum O 0
tolerated O 0
dose O 0
, O 0
malformations B-Disease 0
that O 0
normally O 0
occur O 0
at O 0
low O 0
incidence O 0
, O 0
as O 0
reported O 0
from O 0
previous O 0
single O 0
dose O 0
studies O 0
, O 0
could O 0
also O 0
be O 0
induced O 0
with O 0
ASA B-Chemical 0
given O 0
at O 0
multiple O 0
doses O 0
. O 0

Reversal O 0
of O 0
central O 0
benzodiazepine B-Chemical 0
effects O 0
by O 0
flumazenil B-Chemical 0
after O 0
intravenous O 0
conscious O 0
sedation O 0
with O 0
diazepam B-Chemical 0
and O 0
opioids O 0
: O 0
report O 0
of O 0
a O 0
double O 0
- O 0
blind O 0
multicenter O 0
study O 0
. O 0

The O 0
Flumazenil B-Chemical 0
in O 0
Intravenous O 0
Conscious O 0
Sedation O 0
with O 0
Diazepam B-Chemical 0
Multicenter O 0
Study O 0
Group O 0
II O 0
. O 0

The O 0
efficacy O 0
and O 0
safety O 0
of O 0
a O 0
new O 0
benzodiazepine B-Chemical 0
antagonist O 0
, O 0
flumazenil B-Chemical 0
, O 0
were O 0
assessed O 0
in O 0
a O 0
double O 0
- O 0
blind O 0
multicenter O 0
study O 0
. O 0

Flumazenil B-Chemical 0
( O 0
mean O 0
dose O 0
, O 0
0 O 0
. O 0
76 O 0
mg O 0
) O 0
or O 0
placebo O 0
( O 0
mean O 0
dose O 0
, O 0
8 O 0
. O 0
9 O 0
ml O 0
) O 0
was O 0
administered O 0
intravenously O 0
to O 0
130 O 0
and O 0
67 O 0
patients O 0
, O 0
respectively O 0
, O 0
who O 0
had O 0
been O 0
given O 0
diazepam B-Chemical 0
in O 0
conjunction O 0
with O 0
an O 0
opioid O 0
( O 0
fentanyl B-Chemical 0
, O 0
meperidine B-Chemical 0
, O 0
or O 0
morphine B-Chemical 0
) O 0
for O 0
the O 0
induction O 0
and O 0
maintenance O 0
of O 0
intravenous O 0
conscious O 0
sedation O 0
for O 0
diagnostic O 0
or O 0
therapeutic O 0
surgical O 0
procedures O 0
. O 0

The O 0
group O 0
assessable O 0
for O 0
efficacy O 0
comprised O 0
122 O 0
patients O 0
treated O 0
with O 0
flumazenil B-Chemical 0
and O 0
64 O 0
patients O 0
given O 0
placebo O 0
. O 0

After O 0
5 O 0
minutes O 0
, O 0
80 O 0
/ O 0
115 O 0
( O 0
70 O 0
% O 0
) O 0
flumazenil B-Chemical 0
- O 0
treated O 0
patients O 0
, O 0
compared O 0
with O 0
21 O 0
/ O 0
63 O 0
( O 0
33 O 0
% O 0
) O 0
placebo O 0
- O 0
treated O 0
patients O 0
, O 0
were O 0
completely O 0
awake O 0
and O 0
alert O 0
, O 0
as O 0
indicated O 0
by O 0
a O 0
score O 0
of O 0
5 O 0
on O 0
the O 0
Observer O 0
' O 0
s O 0
Assessment O 0
of O 0
Alertness O 0
/ O 0
Sedation O 0
Scale O 0
. O 0

Ninety O 0
- O 0
five O 0
percent O 0
of O 0
patients O 0
in O 0
each O 0
group O 0
who O 0
attained O 0
a O 0
score O 0
of O 0
5 O 0
at O 0
the O 0
5 O 0
- O 0
minute O 0
assessment O 0
showed O 0
no O 0
loss O 0
of O 0
alertness O 0
throughout O 0
the O 0
180 O 0
- O 0
minute O 0
assessment O 0
period O 0
. O 0

Flumazenil B-Chemical 0
- O 0
treated O 0
patients O 0
also O 0
performed O 0
significantly O 0
better O 0
on O 0
the O 0
Finger O 0
- O 0
to O 0
- O 0
Nose O 0
Test O 0
and O 0
the O 0
recall O 0
of O 0
pictures O 0
shown O 0
at O 0
the O 0
5 O 0
- O 0
minute O 0
assessment O 0
. O 0

Flumazenil B-Chemical 0
was O 0
well O 0
tolerated O 0
, O 0
with O 0
no O 0
serious O 0
adverse O 0
effects O 0
reported O 0
. O 0

Thirty O 0
- O 0
nine O 0
( O 0
30 O 0
% O 0
) O 0
of O 0
flumazenil B-Chemical 0
- O 0
treated O 0
patients O 0
, O 0
compared O 0
with O 0
17 O 0
( O 0
25 O 0
% O 0
) O 0
of O 0
placebo O 0
- O 0
treated O 0
patients O 0
had O 0
one O 0
or O 0
more O 0
drug O 0
- O 0
related O 0
adverse O 0
experiences O 0
. O 0

The O 0
most O 0
common O 0
adverse O 0
effects O 0
were O 0
nausea B-Disease 0
and O 0
vomiting B-Disease 0
in O 0
the O 0
flumazenil B-Chemical 0
group O 0
and O 0
nausea B-Disease 0
and O 0
injection O 0
- O 0
site O 0
pain B-Disease 0
in O 0
the O 0
placebo O 0
group O 0
. O 0

Flumazenil B-Chemical 0
was O 0
found O 0
to O 0
promptly O 0
reverse O 0
sedation O 0
induced O 0
by O 0
diazepam B-Chemical 0
in O 0
the O 0
presence O 0
of O 0
opioids O 0
. O 0

Methylphenidate B-Chemical 0
- O 0
induced O 0
obsessive B-Disease 0
- I-Disease 0
compulsive I-Disease 0
symptoms I-Disease 0
in O 0
an O 0
elderly O 0
man O 0
. O 0

An O 0
82 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
treatment B-Disease 0
- I-Disease 0
resistant I-Disease 0
depression I-Disease 0
and O 0
early O 0
Alzheimer B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
was O 0
started O 0
on O 0
methylphenidate B-Chemical 0
. O 0

Significant O 0
obsessive B-Disease 0
- I-Disease 0
compulsive I-Disease 0
behavior I-Disease 0
ensued O 0
but O 0
diminished O 0
over O 0
several O 0
weeks O 0
when O 0
methylphenidate B-Chemical 0
was O 0
replaced O 0
by O 0
fluvoxamine B-Chemical 0
. O 0

The O 0
patient O 0
had O 0
no O 0
prior O 0
psychiatric B-Disease 0
history O 0
, O 0
but O 0
he O 0
had O 0
a O 0
sister O 0
with O 0
obsessive B-Disease 0
- I-Disease 0
compulsive I-Disease 0
disorder I-Disease 0
. O 0

It O 0
appears O 0
that O 0
methylphenidate B-Chemical 0
precipitated O 0
the O 0
patient O 0
' O 0
s O 0
pathological O 0
behavior O 0
. O 0

Ciprofloxacin B-Chemical 0
- O 0
induced O 0
acute O 0
interstitial B-Disease 0
nephritis I-Disease 0
and O 0
autoimmune B-Disease 0
hemolytic I-Disease 0
anemia I-Disease 0
. O 0

Ciprofloxacin B-Chemical 0
has O 0
been O 0
associated O 0
with O 0
several O 0
side O 0
effects O 0
including O 0
interstitial B-Disease 0
nephritis I-Disease 0
and O 0
hemolytic B-Disease 0
anemia I-Disease 0
. O 0

The O 0
combination O 0
of O 0
both O 0
side O 0
effects O 0
is O 0
extremely O 0
rare O 0
. O 0

In O 0
this O 0
report O 0
, O 0
we O 0
describe O 0
a O 0
case O 0
of O 0
ciprofloxacin B-Chemical 0
- O 0
induced O 0
interstitial B-Disease 0
nephritis I-Disease 0
and O 0
autoimmune B-Disease 0
hemolytic I-Disease 0
anemia I-Disease 0
. O 0

Hemolytic B-Disease 0
anemia I-Disease 0
improved O 0
after O 0
stopping O 0
the O 0
drug O 0
and O 0
initiation O 0
of O 0
steroid B-Chemical 0
therapy O 0
. O 0

Unfortunately O 0
, O 0
acute O 0
interstitial B-Disease 0
nephritis I-Disease 0
was O 0
irreversible O 0
and O 0
the O 0
patient O 0
developed O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
renal I-Disease 0
disease I-Disease 0
. O 0

Potential O 0
deleterious O 0
effect O 0
of O 0
furosemide B-Chemical 0
in O 0
radiocontrast O 0
nephropathy B-Disease 0
. O 0

The O 0
purpose O 0
of O 0
the O 0
study O 0
was O 0
to O 0
determine O 0
the O 0
efficacy O 0
of O 0
furosemide B-Chemical 0
in O 0
addition O 0
to O 0
intravenous O 0
fluids O 0
in O 0
the O 0
prevention O 0
of O 0
radiocontrast O 0
nephropathy B-Disease 0
. O 0

18 O 0
patients O 0
, O 0
referred O 0
to O 0
a O 0
radiocontrast O 0
study O 0
, O 0
considered O 0
at O 0
risk O 0
because O 0
of O 0
preexisting O 0
renal B-Disease 0
insufficiency I-Disease 0
, O 0
were O 0
enrolled O 0
in O 0
a O 0
prospective O 0
, O 0
randomized O 0
, O 0
controlled O 0
trial O 0
, O 0
performed O 0
at O 0
the O 0
secondary O 0
care O 0
center O 0
of O 0
a O 0
1 O 0
, O 0
100 O 0
- O 0
bed O 0
private O 0
university O 0
hospital O 0
. O 0

In O 0
addition O 0
to O 0
fluids O 0
, O 0
the O 0
treatment O 0
group O 0
received O 0
furosemide B-Chemical 0
( O 0
mean O 0
dose O 0
110 O 0
mg O 0
) O 0
intravenously O 0
30 O 0
min O 0
prior O 0
to O 0
the O 0
injection O 0
of O 0
contrast O 0
material O 0
. O 0

The O 0
control O 0
group O 0
received O 0
fluids O 0
( O 0
mean O 0
3 O 0
liters O 0
) O 0
. O 0

Radiological O 0
studies O 0
were O 0
mostly O 0
angiographies O 0
performed O 0
with O 0
both O 0
ionic O 0
and O 0
non O 0
- O 0
ionic O 0
contrast O 0
material O 0
, O 0
at O 0
an O 0
average O 0
dose O 0
of O 0
245 O 0
ml O 0
. O 0

Renal B-Disease 0
function I-Disease 0
significantly I-Disease 0
deteriorated I-Disease 0
in O 0
the O 0
group O 0
pretreated O 0
with O 0
furosemide B-Chemical 0
( O 0
p O 0
< O 0
0 O 0
. O 0
005 O 0
by O 0
ANOVA O 0
) O 0
, O 0
with O 0
a O 0
rise O 0
in O 0
serum O 0
creatinine B-Chemical 0
from O 0
145 O 0
+ O 0
/ O 0
- O 0
13 O 0
to O 0
182 O 0
+ O 0
/ O 0
- O 0
16 O 0
mumol O 0
/ O 0
l O 0
at O 0
24 O 0
h O 0
, O 0
while O 0
no O 0
change O 0
occurred O 0
in O 0
the O 0
control O 0
group O 0
( O 0
from O 0
141 O 0
+ O 0
/ O 0
- O 0
6 O 0
to O 0
142 O 0
+ O 0
/ O 0
- O 0
7 O 0
mumol O 0
/ O 0
l O 0
) O 0
. O 0

Renal B-Disease 0
failure I-Disease 0
was O 0
associated O 0
with O 0
weight B-Disease 0
loss I-Disease 0
in O 0
the O 0
furosemide B-Chemical 0
- O 0
treated O 0
group O 0
. O 0

Furosemide B-Chemical 0
may O 0
be O 0
deleterious O 0
in O 0
the O 0
prevention O 0
of O 0
radiocontrast O 0
nephropathy B-Disease 0
. O 0

Progestational O 0
agents O 0
and O 0
blood B-Disease 0
coagulation I-Disease 0
. O 0

VII O 0
. O 0

Thromboembolic B-Disease 0
and O 0
other O 0
complications O 0
of O 0
oral B-Chemical 0
contraceptive I-Chemical 0
therapy O 0
in O 0
relationship O 0
to O 0
pretreatment O 0
levels O 0
of O 0
blood B-Disease 0
coagulation I-Disease 0
factors O 0
: O 0
summary O 0
report O 0
of O 0
a O 0
ten O 0
- O 0
year O 0
study O 0
. O 0

During O 0
a O 0
ten O 0
- O 0
year O 0
period O 0
, O 0
348 O 0
women O 0
were O 0
studied O 0
for O 0
a O 0
total O 0
of O 0
5 O 0
, O 0
877 O 0
patient O 0
months O 0
in O 0
four O 0
separate O 0
studies O 0
relating O 0
oral B-Chemical 0
contraceptives I-Chemical 0
to O 0
changes O 0
in O 0
hematologic O 0
parameters O 0
. O 0

Significant O 0
increases O 0
in O 0
certain O 0
factors O 0
of O 0
the O 0
blood B-Disease 0
coagulation I-Disease 0
and O 0
fibrinolysin O 0
systems O 0
( O 0
factors O 0
I O 0
, O 0
II O 0
, O 0
VII O 0
, O 0
VIII O 0
, O 0
IX O 0
, O 0
and O 0
X O 0
and O 0
plasminogen O 0
) O 0
were O 0
observed O 0
in O 0
the O 0
treated O 0
groups O 0
. O 0

Severe O 0
complications O 0
developed O 0
in O 0
four O 0
patients O 0
. O 0

All O 0
four O 0
had O 0
an O 0
abnormal O 0
blood B-Disease 0
coagulation I-Disease 0
profile O 0
, O 0
suggesting O 0
" O 0
hypercoagulability B-Disease 0
" O 0
before O 0
initiation O 0
of O 0
therapy O 0
. O 0

Some O 0
of O 0
these O 0
findings O 0
represented O 0
the O 0
most O 0
extreme O 0
abnormalities O 0
seen O 0
in O 0
the O 0
entire O 0
group O 0
of O 0
patients O 0
; O 0
some O 0
increased O 0
further O 0
during O 0
therapy O 0
. O 0

One O 0
of O 0
these O 0
patients O 0
developed O 0
a O 0
myocardial B-Disease 0
infarction I-Disease 0
before O 0
receiving O 0
any O 0
medication O 0
, O 0
shortly O 0
after O 0
the O 0
base O 0
- O 0
line O 0
values O 0
were O 0
obtained O 0
. O 0

One O 0
patient O 0
developed O 0
retinopathy B-Disease 0
19 O 0
months O 0
after O 0
she O 0
began O 0
therapy O 0
, O 0
and O 0
another O 0
developed O 0
thrombophlebitis B-Disease 0
after O 0
27 O 0
months O 0
of O 0
therapy O 0
. O 0

The O 0
fourth O 0
patient O 0
developed O 0
thrombophlebitis B-Disease 0
14 O 0
days O 0
after O 0
initiation O 0
of O 0
contraceptive O 0
therapy O 0
. O 0

All O 0
four O 0
patients O 0
were O 0
of O 0
the O 0
A O 0
or O 0
AB O 0
blood O 0
group O 0
. O 0

Previous O 0
studies O 0
suggested O 0
the O 0
possiblility O 0
of O 0
increased O 0
propensity O 0
for O 0
thromboembolic B-Disease 0
episodes I-Disease 0
in O 0
patients O 0
possessing O 0
the O 0
A O 0
antigen O 0
. O 0

It O 0
appears O 0
from O 0
these O 0
data O 0
that O 0
hematologic O 0
work O 0
- O 0
ups O 0
may O 0
be O 0
useful O 0
in O 0
women O 0
who O 0
are O 0
about O 0
to O 0
start O 0
long O 0
- O 0
term O 0
oral B-Chemical 0
contraceptive I-Chemical 0
therapy O 0
. O 0

Orthostatic B-Disease 0
hypotension I-Disease 0
occurs O 0
following O 0
alpha O 0
2 O 0
- O 0
adrenoceptor O 0
blockade O 0
in O 0
chronic O 0
prazosin B-Chemical 0
- O 0
pretreated O 0
conscious O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
. O 0

1 O 0
. O 0

Studies O 0
were O 0
performed O 0
to O 0
evaluate O 0
whether O 0
chronic O 0
prazosin B-Chemical 0
treatment O 0
alters O 0
the O 0
alpha O 0
2 O 0
- O 0
adrenoceptor O 0
function O 0
for O 0
orthostatic O 0
control O 0
of O 0
arterial O 0
blood O 0
pressure O 0
in O 0
conscious O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
( O 0
SHR O 0
) O 0
. O 0

2 O 0
. O 0

Conscious O 0
SHR O 0
( O 0
male O 0
300 O 0
- O 0
350 O 0
g O 0
) O 0
were O 0
subjected O 0
to O 0
90 O 0
degrees O 0
head O 0
- O 0
up O 0
tilts O 0
for O 0
60 O 0
s O 0
following O 0
acute O 0
administration O 0
of O 0
prazosin B-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
mg O 0
kg O 0
- O 0
1 O 0
i O 0
. O 0
p O 0
. O 0
) O 0
or O 0
rauwolscine B-Chemical 0
( O 0
3 O 0
mg O 0
kg O 0
- O 0
1 O 0
i O 0
. O 0
v O 0
. O 0
) O 0
. O 0

Orthostatic B-Disease 0
hypotension I-Disease 0
was O 0
determined O 0
by O 0
the O 0
average O 0
decrease O 0
( O 0
% O 0
) O 0
in O 0
mean O 0
arterial O 0
pressure O 0
( O 0
MAP O 0
femoral O 0
) O 0
over O 0
the O 0
60 O 0
- O 0
s O 0
tilt O 0
period O 0
. O 0

The O 0
basal O 0
MAP O 0
of O 0
conscious O 0
SHR O 0
was O 0
reduced O 0
to O 0
a O 0
similar O 0
extent O 0
by O 0
prazosin B-Chemical 0
( O 0
- O 0
23 O 0
% O 0
( O 0
- O 0
) O 0
- O 0
26 O 0
% O 0
MAP O 0
) O 0
and O 0
rauwolscine B-Chemical 0
( O 0
- O 0
16 O 0
% O 0
( O 0
- O 0
) O 0
- O 0
33 O 0
% O 0
MAP O 0
) O 0
. O 0

However O 0
, O 0
the O 0
head O 0
- O 0
up O 0
tilt O 0
induced O 0
orthostatic B-Disease 0
hypotension I-Disease 0
in O 0
the O 0
SHR O 0
treated O 0
with O 0
prazosin B-Chemical 0
( O 0
- O 0
16 O 0
% O 0
MAP O 0
, O 0
n O 0
= O 0
6 O 0
) O 0
, O 0
but O 0
not O 0
in O 0
the O 0
SHR O 0
treated O 0
with O 0
rauwolscine B-Chemical 0
( O 0
less O 0
than O 0
+ O 0
2 O 0
% O 0
MAP O 0
, O 0
n O 0
= O 0
6 O 0
) O 0
. O 0

3 O 0
. O 0

Conscious O 0
SHR O 0
were O 0
treated O 0
for O 0
4 O 0
days O 0
with O 0
prazosin B-Chemical 0
at O 0
2 O 0
mg O 0
kg O 0
- O 0
1 O 0
day O 0
- O 0
1 O 0
i O 0
. O 0
p O 0
. O 0
for O 0
chronic O 0
alpha O 0
1 O 0
- O 0
adrenoceptor O 0
blockade O 0
. O 0

MAP O 0
in O 0
conscious O 0
SHR O 0
after O 0
chronic O 0
prazosin B-Chemical 0
treatment O 0
was O 0
14 O 0
% O 0
lower O 0
than O 0
in O 0
the O 0
untreated O 0
SHR O 0
( O 0
n O 0
= O 0
8 O 0
) O 0
. O 0

Head O 0
- O 0
up O 0
tilts O 0
in O 0
these O 0
rats O 0
did O 0
not O 0
produce O 0
orthostatic B-Disease 0
hypotension I-Disease 0
when O 0
performed O 0
either O 0
prior O 0
to O 0
or O 0
after O 0
acute O 0
dosing O 0
of O 0
prazosin B-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
mg O 0
kg O 0
- O 0
1 O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

Conversely O 0
, O 0
administration O 0
of O 0
rauwolscine B-Chemical 0
( O 0
3 O 0
mg O 0
kg O 0
- O 0
1 O 0
i O 0
. O 0
v O 0
. O 0
) O 0
in O 0
chronic O 0
prazosin B-Chemical 0
treated O 0
SHR O 0
decreased O 0
the O 0
basal O 0
MAP O 0
by O 0
12 O 0
- O 0
31 O 0
% O 0
( O 0
n O 0
= O 0
4 O 0
) O 0
, O 0
and O 0
subsequent O 0
tilts O 0
induced O 0
further O 0
drops O 0
of O 0
MAP O 0
by O 0
19 O 0
- O 0
23 O 0
% O 0
in O 0
these O 0
rats O 0
. O 0

4 O 0
. O 0

The O 0
pressor O 0
responses O 0
and O 0
bradycardia B-Disease 0
to O 0
the O 0
alpha O 0
1 O 0
- O 0
agonist O 0
cirazoline B-Chemical 0
( O 0
0 O 0
. O 0
6 O 0
and O 0
2 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
i O 0
. O 0
v O 0
. O 0
) O 0
, O 0
the O 0
alpha O 0
2 O 0
- O 0
agonist O 0
Abbott B-Chemical 0
- I-Chemical 0
53693 I-Chemical 0
( O 0
1 O 0
and O 0
3 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
i O 0
. O 0
v O 0
. O 0
) O 0
, O 0
and O 0
noradrenaline B-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
and O 0
1 O 0
. O 0
0 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
i O 0
. O 0
v O 0
. O 0
) O 0
were O 0
determined O 0
in O 0
conscious O 0
SHR O 0
with O 0
and O 0
without O 0
chronic O 0
prazosin B-Chemical 0
pretreatment O 0
. O 0

Both O 0
the O 0
pressor O 0
and O 0
bradycardia B-Disease 0
effects O 0
of O 0
cirazoline B-Chemical 0
were O 0
abolished O 0
in O 0
chronic O 0
prazosin B-Chemical 0
treated O 0
SHR O 0
( O 0
n O 0
= O 0
4 O 0
) O 0
as O 0
compared O 0
to O 0
the O 0
untreated O 0
SHR O 0
( O 0
n O 0
= O 0
4 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
effects O 0
of O 0
Abbott B-Chemical 0
- I-Chemical 0
53693 I-Chemical 0
were O 0
similar O 0
in O 0
both O 0
groups O 0
of O 0
SHR O 0
, O 0
but O 0
the O 0
accompanying O 0
bradycardia B-Disease 0
was O 0
greater O 0
in O 0
SHR O 0
with O 0
chronic O 0
prazosin B-Chemical 0
treatment O 0
than O 0
without O 0
such O 0
treatment O 0
. O 0

Furthermore O 0
, O 0
the O 0
bradycardia B-Disease 0
that O 0
accompanied O 0
the O 0
noradrenaline B-Chemical 0
- O 0
induced O 0
pressor O 0
effect O 0
in O 0
SHR O 0
was O 0
similar O 0
with O 0
and O 0
without O 0
chronic O 0
prazosin B-Chemical 0
treatment O 0
despite O 0
a O 0
47 O 0
- O 0
71 O 0
% O 0
reduction O 0
of O 0
the O 0
pressor O 0
effect O 0
in O 0
chronic O 0
alpha O 0
1 O 0
- O 0
receptor O 0
blocked O 0
SHR O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
400 O 0
WORDS O 0
) O 0

Hemolytic B-Disease 0
- I-Disease 0
uremic I-Disease 0
syndrome I-Disease 0
associated O 0
with O 0
ingestion O 0
of O 0
quinine B-Chemical 0
. O 0

Hemolytic B-Disease 0
- I-Disease 0
uremic I-Disease 0
syndrome I-Disease 0
following O 0
quinine B-Chemical 0
ingestion O 0
is O 0
a O 0
newly O 0
described O 0
phenomenon O 0
, O 0
with O 0
just O 0
two O 0
previous O 0
descriptions O 0
of O 0
4 O 0
cases O 0
in O 0
the O 0
literature O 0
. O 0

We O 0
describe O 0
a O 0
5th O 0
case O 0
. O 0

The O 0
reaction O 0
may O 0
be O 0
mediated O 0
by O 0
the O 0
presence O 0
of O 0
antibodies O 0
reactive O 0
against O 0
platelets O 0
in O 0
the O 0
presence O 0
of O 0
quinine B-Chemical 0
. O 0

Treatment O 0
has O 0
included O 0
use O 0
of O 0
plasma O 0
exchange O 0
, O 0
prednisone B-Chemical 0
, O 0
aspirin B-Chemical 0
, O 0
and O 0
dipyridamole B-Chemical 0
. O 0

The O 0
patients O 0
have O 0
all O 0
regained O 0
some O 0
degree O 0
of O 0
renal O 0
function O 0
. O 0

However O 0
, O 0
it O 0
is O 0
unclear O 0
whether O 0
pharmacological O 0
treatment O 0
or O 0
spontaneous O 0
resolution O 0
is O 0
responsible O 0
for O 0
the O 0
improvement O 0
. O 0

Quinine B-Chemical 0
- O 0
associated O 0
hemolytic B-Disease 0
- I-Disease 0
uremic I-Disease 0
syndrome I-Disease 0
probably O 0
occurs O 0
more O 0
often O 0
than O 0
is O 0
recognized O 0
. O 0

It O 0
is O 0
important O 0
to O 0
recognize O 0
this O 0
reaction O 0
when O 0
it O 0
occurs O 0
and O 0
to O 0
avoid O 0
further O 0
quinine B-Chemical 0
exposure O 0
, O 0
since O 0
the O 0
reaction O 0
seems O 0
to O 0
be O 0
recurrent O 0
. O 0

Amnestic B-Disease 0
syndrome I-Disease 0
associated O 0
with O 0
propranolol B-Chemical 0
toxicity B-Disease 0
: O 0
a O 0
case O 0
report O 0
. O 0

An O 0
elderly O 0
woman O 0
developed O 0
an O 0
Alzheimer B-Disease 0
- O 0
like O 0
subacute O 0
dementia B-Disease 0
as O 0
a O 0
result O 0
of O 0
propranolol B-Chemical 0
toxicity B-Disease 0
. O 0

Analysis O 0
of O 0
the O 0
manifestations O 0
showed O 0
that O 0
severe O 0
impairment O 0
of O 0
memory O 0
accounted O 0
for O 0
virtually O 0
all O 0
of O 0
the O 0
abnormalities O 0
. O 0

There O 0
is O 0
evidence O 0
that O 0
cerebral O 0
reactions O 0
to O 0
drug O 0
toxicity B-Disease 0
can O 0
exhibit O 0
patterns O 0
that O 0
suggest O 0
highly O 0
selective O 0
involvement O 0
of O 0
functional O 0
subdivisions O 0
of O 0
the O 0
brain O 0
. O 0

Cefotetan B-Chemical 0
- O 0
induced O 0
immune O 0
hemolytic B-Disease 0
anemia I-Disease 0
. O 0

Immune O 0
hemolytic B-Disease 0
anemia I-Disease 0
due O 0
to O 0
a O 0
drug O 0
- O 0
adsorption O 0
mechanism O 0
has O 0
been O 0
described O 0
primarily O 0
in O 0
patients O 0
receiving O 0
penicillins B-Chemical 0
and O 0
first O 0
- O 0
generation O 0
cephalosporins B-Chemical 0
. O 0

We O 0
describe O 0
a O 0
patient O 0
who O 0
developed O 0
anemia B-Disease 0
while O 0
receiving O 0
intravenous O 0
cefotetan B-Chemical 0
. O 0

Cefotetan B-Chemical 0
- O 0
dependent O 0
antibodies O 0
were 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
an O 0
eluate O 0
prepared O 0
from O 0
his O 0
red O 0
blood O 0
cells O 0
. O 0

The O 0
eluate O 0
also O 0
reacted O 0
weakly O 0
with O 0
red O 0
blood O 0
cells O 0
in O 0
the O 0
absence O 0
of O 0
cefotetan B-Chemical 0
, O 0
suggesting O 0
the O 0
concomitant O 0
formation O 0
of O 0
warm O 0
- O 0
reactive O 0
autoantibodies O 0
. O 0

These O 0
observations O 0
, O 0
in O 0
conjunction O 0
with O 0
clinical O 0
and O 0
laboratory O 0
evidence O 0
of O 0
extravascular O 0
hemolysis B-Disease 0
, O 0
are O 0
consistent O 0
with O 0
drug O 0
- O 0
induced O 0
hemolytic B-Disease 0
anemia I-Disease 0
, O 0
possibly O 0
involving O 0
both O 0
drug O 0
- O 0
adsorption O 0
and O 0
autoantibody O 0
formation O 0
mechanisms O 0
. O 0

This O 0
case O 0
emphasizes O 0
the O 0
need O 0
for O 0
increased O 0
awareness O 0
of O 0
hemolytic O 0
reactions O 0
to O 0
all O 0
cephalosporins B-Chemical 0
. O 0

Use O 0
of O 0
dexamethasone B-Chemical 0
with O 0
mesna B-Chemical 0
for O 0
the O 0
prevention O 0
of O 0
ifosfamide B-Chemical 0
- O 0
induced O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
. O 0

AIM O 0
: O 0
Hemorrhagic B-Disease 0
cystitis I-Disease 0
( O 0
HC B-Disease 0
) O 0
is O 0
a O 0
limiting O 0
side O 0
- O 0
effect O 0
of O 0
chemotherapy O 0
with O 0
ifosfamide B-Chemical 0
( O 0
IFS B-Chemical 0
) O 0
. O 0

In O 0
the O 0
study O 0
presented O 0
here O 0
, O 0
we O 0
investigated O 0
the O 0
use O 0
of O 0
dexamethasone B-Chemical 0
in O 0
combination O 0
with O 0
mesna B-Chemical 0
for O 0
the O 0
prevention O 0
of O 0
IFS B-Chemical 0
- O 0
induced O 0
HC B-Disease 0
. O 0

METHODS O 0
: O 0
Male O 0
Wistar O 0
rats O 0
( O 0
150 O 0
- O 0
200 O 0
g O 0
; O 0
6 O 0
rats O 0
per O 0
group O 0
) O 0
were O 0
treated O 0
with O 0
saline O 0
or O 0
mesna B-Chemical 0
5 O 0
min O 0
( O 0
i O 0
. O 0
p O 0
. O 0
) O 0
before O 0
and O 0
2 O 0
and O 0
6 O 0
h O 0
after O 0
( O 0
v O 0
. O 0
o O 0
. O 0
) O 0
administration O 0
of O 0
IFS B-Chemical 0
. O 0

One O 0
, O 0
two O 0
or O 0
three O 0
doses O 0
of O 0
mesna B-Chemical 0
were O 0
replaced O 0
with O 0
dexamethasone B-Chemical 0
alone O 0
or O 0
with O 0
dexamethasone B-Chemical 0
plus O 0
mesna B-Chemical 0
. O 0

Cystitis B-Disease 0
was O 0
evaluated O 0
24 O 0
h O 0
after O 0
its O 0
induction O 0
by O 0
the O 0
changes O 0
in O 0
bladder O 0
wet O 0
weight O 0
and O 0
by O 0
macroscopic O 0
and O 0
microscopic O 0
analysis O 0
. O 0

RESULTS O 0
: O 0
The O 0
replacement O 0
of O 0
the O 0
last O 0
dose O 0
or O 0
the O 0
last O 0
two O 0
doses O 0
of O 0
mesna B-Chemical 0
with O 0
dexamethasone B-Chemical 0
reduced O 0
the O 0
increase O 0
in O 0
bladder O 0
wet O 0
weight O 0
induced O 0
by O 0
IFS B-Chemical 0
by O 0
84 O 0
. O 0
79 O 0
% O 0
and O 0
89 O 0
. O 0
13 O 0
% O 0
, O 0
respectively O 0
. O 0

In O 0
addition O 0
, O 0
it O 0
almost O 0
abolished O 0
the O 0
macroscopic O 0
and O 0
microscopic O 0
alterations O 0
induced O 0
by O 0
IFS B-Chemical 0
. O 0

Moreover O 0
, O 0
the O 0
addition O 0
of O 0
dexamethasone B-Chemical 0
to O 0
the O 0
last O 0
two O 0
doses O 0
of O 0
mesna B-Chemical 0
was O 0
more O 0
efficient O 0
than O 0
three O 0
doses O 0
of O 0
mesna B-Chemical 0
alone O 0
when O 0
evaluated O 0
microscopically O 0
. O 0

CONCLUSION O 0
: O 0
Dexamethasone B-Chemical 0
in O 0
combination O 0
with O 0
mesna B-Chemical 0
was O 0
efficient O 0
in O 0
blocking O 0
IFS B-Chemical 0
- O 0
induced O 0
HC B-Disease 0
. O 0

However O 0
, O 0
the O 0
replacement O 0
of O 0
last O 0
two O 0
doses O 0
of O 0
mesna B-Chemical 0
with O 0
saline O 0
or O 0
all O 0
of O 0
the O 0
mesna B-Chemical 0
doses O 0
with O 0
dexamethasone B-Chemical 0
did O 0
not O 0
prevent O 0
HC B-Disease 0
. 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
induced O 0
erythema B-Disease 0
nodosum I-Disease 0
in O 0
patients O 0
with O 0
acute B-Disease 0
promyelocytic I-Disease 0
leukemia I-Disease 0
. O 0

Erythema B-Disease 0
nodosum I-Disease 0
associated 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
for O 0
acute B-Disease 0
promyelocytic I-Disease 0
leukemia I-Disease 0
( O 0
APL B-Disease 0
) O 0
is O 0
very O 0
rare O 0
. O 0

We O 0
describe O 0
four O 0
patients O 0
with O 0
classic O 0
APL B-Disease 0
who O 0
developed O 0
erythema B-Disease 0
nodosum I-Disease 0
during O 0
ATRA B-Chemical 0
therapy O 0
. O 0

Fever B-Disease 0
and O 0
subsequent O 0
multiple O 0
painful B-Disease 0
erythematous B-Disease 0
nodules I-Disease 0
over O 0
extremities O 0
developed O 0
on O 0
D11 O 0
, O 0
D16 O 0
, O 0
D17 O 0
, O 0
and O 0
D19 O 0
, O 0
respectively O 0
, O 0
after O 0
ATRA B-Chemical 0
therapy O 0
. O 0

The O 0
skin O 0
biopsy O 0
taken O 0
from O 0
each O 0
patient O 0
was O 0
consistent O 0
with O 0
erythema B-Disease 0
nodosum I-Disease 0
. O 0

All O 0
patients O 0
received O 0
short O 0
course O 0
of O 0
steroids B-Chemical 0
. O 0

Fever B-Disease 0
subsided O 0
rapidly O 0
and O 0
the O 0
skin O 0
lesions O 0
regressed O 0
completely O 0
. O 0

All O 0
patients O 0
achieved O 0
complete O 0
remission O 0
without O 0
withdrawal O 0
of O 0
ATRA B-Chemical 0
. O 0

ATRA B-Chemical 0
seemed O 0
to O 0
be O 0
the O 0
most O 0
possible O 0
etiology O 0
of O 0
erythema B-Disease 0
nodosum I-Disease 0
in O 0
our O 0
patients O 0
. O 0

Short O 0
- O 0
term O 0
use O 0
of O 0
steroid B-Chemical 0
is O 0
very O 0
effective O 0
in O 0
ATRA B-Chemical 0
- O 0
induced O 0
erythema B-Disease 0
nodosum I-Disease 0
. O 0

Effect O 0
of O 0
some O 0
convulsants O 0
on O 0
the O 0
protective O 0
activity O 0
of O 0
loreclezole B-Chemical 0
and O 0
its O 0
combinations O 0
with O 0
valproate B-Chemical 0
or O 0
clonazepam B-Chemical 0
in O 0
amygdala O 0
- O 0
kindled O 0
rats O 0
. O 0

Loreclezole B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
exerted O 0
a O 0
significant O 0
protective O 0
action O 0
in O 0
amygdala O 0
- O 0
kindled O 0
rats O 0
, O 0
reducing O 0
both O 0
seizure B-Disease 0
and O 0
afterdischarge O 0
durations O 0
. O 0

The O 0
combinations O 0
of O 0
loreclezole B-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
with O 0
valproate B-Chemical 0
, O 0
clonazepam B-Chemical 0
, O 0
or O 0
carbamazepine B-Chemical 0
( O 0
applied O 0
at O 0
their O 0
subprotective O 0
doses O 0
) O 0
also O 0
exhibited O 0
antiseizure O 0
effect O 0
in O 0
this O 0
test O 0
. O 0

However O 0
, O 0
only O 0
two O 0
first O 0
combinations O 0
occurred O 0
to O 0
be O 0
of O 0
pharmacodynamic O 0
nature O 0
. O 0

Among O 0
several O 0
chemoconvulsants O 0
, O 0
bicuculline 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
aspartic I-Chemical 0
acid I-Chemical 0
and O 0
BAY B-Chemical 0
k I-Chemical 0
- I-Chemical 0
8644 I-Chemical 0
( O 0
the O 0
opener O 0
of O 0
L O 0
- O 0
type O 0
calcium B-Chemical 0
channels O 0
) O 0
reversed O 0
the O 0
protective O 0
activity O 0
of O 0
loreclezole B-Chemical 0
alone O 0
and O 0
its O 0
combination O 0
with O 0
valproate B-Chemical 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
bicuculline B-Chemical 0
, O 0
aminophylline B-Chemical 0
and O 0
BAY B-Chemical 0
k I-Chemical 0
- I-Chemical 0
8644 I-Chemical 0
inhibited O 0
the O 0
anticonvulsive O 0
action O 0
of O 0
loreclezole B-Chemical 0
combined O 0
with O 0
clonazepam B-Chemical 0
. O 0

The O 0
results O 0
support O 0
the O 0
hypothesis O 0
that O 0
the O 0
protective O 0
activity O 0
of O 0
loreclezole B-Chemical 0
and O 0
its O 0
combinations O 0
with O 0
other O 0
antiepileptics O 0
may O 0
involve O 0
potentiation O 0
of O 0
GABAergic O 0
neurotransmission O 0
and O 0
blockade O 0
of O 0
L O 0
- O 0
type O 0
of O 0
calcium B-Chemical 0
channels O 0
. O 0

Mitochondrial O 0
DNA O 0
and O 0
its O 0
respiratory O 0
chain O 0
products O 0
are O 0
defective O 0
in O 0
doxorubicin B-Chemical 0
nephrosis B-Disease 0
. O 0

BACKGROUND O 0
: O 0
Doxorubicin B-Chemical 0
induces O 0
a O 0
self O 0
- O 0
perpetuating O 0
nephropathy B-Disease 0
characterized O 0
by O 0
early O 0
glomerular B-Disease 0
and I-Disease 0
late I-Disease 0
- I-Disease 0
onset I-Disease 0
tubular I-Disease 0
lesions I-Disease 0
in O 0
rats O 0
. O 0

We O 0
investigated O 0
the O 0
potential O 0
role O 0
of O 0
mitochondrial B-Disease 0
injury I-Disease 0
in O 0
the O 0
onset O 0
of O 0
these O 0
lesions O 0
. O 0

METHODS O 0
: O 0
Rats O 0
were O 0
treated O 0
with O 0
intravenous O 0
doxorubicin B-Chemical 0
( O 0
1 O 0
mg O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
week O 0
( O 0
- O 0
1 O 0
) O 0
) O 0
for O 0
7 O 0
weeks O 0
and O 0
were O 0
sacrificed O 0
either O 0
1 O 0
week O 0
( O 0
' O 0
short O 0
- O 0
term O 0
' O 0
) O 0
or O 0
30 O 0
weeks O 0
( O 0
' O 0
long O 0
- O 0
term O 0
' O 0
) O 0
following O 0
the O 0
last O 0
dose O 0
. O 0

Additional O 0
rats O 0
received O 0
a O 0
single O 0
dose O 0
either O 0
6 O 0
days O 0
or O 0
2 O 0
h O 0
prior O 0
to O 0
euthanasia O 0
. O 0

All O 0
rats O 0
were O 0
killed O 0
at O 0
48 O 0
weeks O 0
of O 0
age O 0
. O 0

Glomerular B-Disease 0
and I-Disease 0
tubular I-Disease 0
injury I-Disease 0
was O 0
monitored O 0
and O 0
correlated O 0
to O 0
the O 0
activity O 0
or O 0
expression O 0
of O 0
respiratory O 0
chain O 0
components O 0
. O 0

Finally O 0
, O 0
we O 0
quantified O 0
both O 0
nuclear O 0
and O 0
mitochondrial O 0
DNA O 0
( O 0
mtDNA O 0
) O 0
as O 0
well O 0
as O 0
superoxide B-Chemical 0
production O 0
and O 0
the O 0
4834 O 0
base O 0
pair O 0
' O 0
common O 0
' O 0
mtDNA O 0
deletion O 0
. O 0

RESULTS O 0
: O 0
The O 0
' O 0
long O 0
- O 0
term O 0
' O 0
group O 0
had O 0
significant O 0
glomerular B-Disease 0
and I-Disease 0
tubular I-Disease 0
lesions I-Disease 0
, O 0
depressed O 0
activities O 0
of O 0
mtDNA O 0
- O 0
encoded O 0
NADH O 0
dehydrogenase O 0
and O 0
cytochrome O 0
- O 0
c O 0
oxidase O 0
( O 0
COX O 0
) O 0
and O 0
increased O 0
citrate B-Chemical 0
synthase O 0
activity O 0
. O 0

In O 0
addition O 0
, O 0
expression O 0
of O 0
the O 0
mtDNA O 0
- O 0
encoded O 0
COX O 0
subunit O 0
I O 0
was O 0
reduced O 0
and O 0
mtDNA O 0
levels O 0
were O 0
decreased O 0
. O 0

In O 0
' O 0
short O 0
- O 0
term O 0
' O 0
rats O 0
, O 0
there O 0
were O 0
fewer O 0
tubular B-Disease 0
lesions I-Disease 0
, O 0
but O 0
similar O 0
numbers O 0
of O 0
glomerular B-Disease 0
lesions I-Disease 0
activity O 0
. O 0

Among O 0
all O 0
animals O 0
, O 0
glomerular B-Disease 0
and I-Disease 0
tubular I-Disease 0
injury I-Disease 0
were O 0
inversely O 0
correlated O 0
with O 0
mtDNA O 0
levels O 0
, O 0
mtDNA O 0
- O 0
encoded O 0
respiratory O 0
chain O 0
activities O 0
and O 0
with O 0
the O 0
expression O 0
of O 0
the O 0
mtDNA O 0
- O 0
encoded O 0
respiratory O 0
chain O 0
subunit O 0
COX O 0
- O 0
I O 0
. O 0

Injury O 0
was O 0
positively O 0
correlated O 0
with O 0
superoxide B-Chemical 0
production O 0
and O 0
the O 0
activities O 0
of O 0
nucleus O 0
- O 0
encoded O 0
mitochondrial O 0
or O 0
cytoplasmic O 0
enzymes O 0
. O 0

Kidneys O 0
from O 0
the O 0
' O 0
long O 0
- O 0
term O 0
' O 0
group O 0
showed O 0
more O 0
mtDNA O 0
deletions O 0
than O 0
in O 0
' O 0
short O 0
- O 0
term O 0
' O 0
animals O 0
and O 0
these O 0
were O 0
not O 0
observed O 0
in O 0
the O 0
other O 0
groups O 0
. O 0

CONCLUSIONS O 0
: O 0
These O 0
results O 0
suggest O 0
an O 0
important O 0
role O 0
for O 0
quantitative O 0
and O 0
qualitative O 0
mtDNA O 0
alterations O 0
through O 0
the O 0
reduction O 0
of O 0
mtDNA O 0
- O 0
encoded O 0
respiratory O 0
chain O 0
function O 0
and O 0
induction O 0
of O 0
superoxide B-Chemical 0
in O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
renal B-Disease 0
lesions I-Disease 0
. O 0

A O 0
randomized O 0
, O 0
placebo O 0
- O 0
controlled O 0
, O 0
crossover O 0
study O 0
of O 0
ephedrine B-Chemical 0
for O 0
SSRI O 0
- O 0
induced O 0
female O 0
sexual B-Disease 0
dysfunction I-Disease 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
whether O 0
ephedrine B-Chemical 0
, O 0
an O 0
alpha O 0
- O 0
and O 0
beta O 0
- O 0
adrenergic O 0
agonist O 0
previously O 0
shown O 0
to O 0
enhance O 0
genital O 0
blood O 0
flow O 0
in O 0
women O 0
, O 0
has O 0
beneficial O 0
effects O 0
in O 0
reversing O 0
antidepressant O 0
- O 0
induced O 0
sexual B-Disease 0
dysfunction I-Disease 0
. O 0

Nineteen O 0
sexually B-Disease 0
dysfunctional I-Disease 0
women O 0
receiving O 0
either O 0
fluoxetine B-Chemical 0
, O 0
sertraline B-Chemical 0
, O 0
or O 0
paroxetine B-Chemical 0
participated O 0
in O 0
an O 0
eight O 0
- O 0
week O 0
, 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
of O 0
the O 0
effects O 0
of O 0
ephedrine B-Chemical 0
( O 0
50 O 0
mg O 0
) O 0
on O 0
self O 0
- O 0
report O 0
measures O 0
of O 0
sexual O 0
desire O 0
, O 0
arousal O 0
, O 0
orgasm O 0
, O 0
and O 0
sexual O 0
satisfaction O 0
. O 0

Although O 0
there O 0
were O 0
significant O 0
improvements O 0
relative O 0
to O 0
baseline O 0
in O 0
sexual O 0
desire O 0
and O 0
orgasm O 0
intensity O 0
/ O 0
pleasure O 0
on O 0
50 O 0
mg O 0
ephedrine B-Chemical 0
1 O 0
- O 0
hr O 0
prior O 0
to O 0
sexual O 0
activity O 0
, O 0
significant O 0
improvements O 0
in O 0
these O 0
measures O 0
, O 0
as O 0
well O 0
as O 0
in O 0
sexual O 0
arousal O 0
and O 0
orgasmic O 0
ability O 0
also O 0
were O 0
noted O 0
with O 0
placebo O 0
. O 0

These O 0
findings O 0
highlight O 0
the O 0
importance O 0
of O 0
conducting O 0
placebo O 0
- O 0
controlled O 0
trials O 0
for O 0
this O 0
condition O 0
. O 0

Does O 0
hormone O 0
therapy O 0
for O 0
the O 0
treatment O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
have O 0
a O 0
detrimental B-Disease 0
effect I-Disease 0
on I-Disease 0
memory I-Disease 0
and I-Disease 0
cognition I-Disease 0
? O 0

A O 0
pilot O 0
study O 0
. O 0

This O 0
pilot O 0
study O 0
examines O 0
whether O 0
hormone O 0
therapy O 0
for O 0
breast B-Disease 0
cancer I-Disease 0
affects O 0
cognition O 0
. O 0

Patients O 0
participating O 0
in O 0
a O 0
randomised O 0
trial O 0
of O 0
anastrozole B-Chemical 0
, O 0
tamoxifen B-Chemical 0
alone O 0
or O 0
combined O 0
( O 0
ATAC O 0
) O 0
( O 0
n O 0
= O 0
94 O 0
) O 0
and O 0
a O 0
group O 0
of O 0
women O 0
without O 0
breast B-Disease 0
cancer I-Disease 0
( O 0
n O 0
= O 0
35 O 0
) O 0
completed O 0
a O 0
battery O 0
of O 0
neuropsychological O 0
measures O 0
. O 0

Compared O 0
with O 0
the O 0
control O 0
group O 0
, O 0
the O 0
patients O 0
were O 0
impaired O 0
on O 0
a O 0
processing O 0
speed O 0
task O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
032 O 0
) O 0
and O 0
on O 0
a O 0
measure O 0
of O 0
immediate O 0
verbal O 0
memory O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
026 O 0
) O 0
after O 0
controlling O 0
for O 0
the O 0
use O 0
of O 0
hormone O 0
replacement O 0
therapy O 0
in O 0
both O 0
groups O 0
. O 0

Patient O 0
group O 0
performance O 0
was O 0
not O 0
significantly O 0
related O 0
to O 0
length O 0
of O 0
treatment O 0
or O 0
measures O 0
of O 0
psychological O 0
morbidity O 0
. O 0

The O 0
results O 0
showed O 0
specific O 0
impairments O 0
in O 0
processing O 0
speed O 0
and O 0
verbal O 0
memory O 0
in O 0
women O 0
receiving O 0
hormonal O 0
therapy O 0
for O 0
the O 0
treatment O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

Verbal O 0
memory O 0
may O 0
be O 0
especially O 0
sensitive O 0
to O 0
changes O 0
in O 0
oestrogen B-Chemical 0
levels O 0
, O 0
a O 0
finding O 0
commonly O 0
reported O 0
in O 0
studies O 0
of O 0
hormone O 0
replacement O 0
therapy O 0
in O 0
healthy O 0
women O 0
. O 0

In O 0
view O 0
of O 0
the O 0
increased O 0
use O 0
of O 0
hormone O 0
therapies O 0
in O 0
an O 0
adjuvant O 0
and O 0
preventative O 0
setting O 0
their O 0
impact O 0
on O 0
cognitive O 0
functioning O 0
should O 0
be O 0
investigated O 0
more O 0
thoroughly O 0
. O 0

Expression O 0
of O 0
p300 O 0
protects O 0
cardiac O 0
myocytes O 0
from O 0
apoptosis O 0
in O 0
vivo O 0
. O 0

Doxorubicin B-Chemical 0
is O 0
an O 0
anti O 0
- O 0
tumor B-Disease 0
agent O 0
that O 0
represses O 0
cardiac O 0
- O 0
specific O 0
gene O 0
expression O 0
and O 0
induces O 0
myocardial O 0
cell O 0
apoptosis O 0
. O 0

Doxorubicin B-Chemical 0
depletes O 0
cardiac O 0
p300 O 0
, O 0
a O 0
transcriptional O 0
coactivator O 0
that O 0
is O 0
required O 0
for O 0
the O 0
maintenance O 0
of O 0
the O 0
differentiated O 0
phenotype O 0
of O 0
cardiac O 0
myocytes O 0
. O 0

However O 0
, O 0
the O 0
role O 0
of O 0
p300 O 0
in O 0
protection O 0
against O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
apoptosis O 0
is O 0
unknown O 0
. O 0

Transgenic O 0
mice O 0
overexpressing O 0
p300 O 0
in O 0
the O 0
heart O 0
and O 0
wild O 0
- O 0
type O 0
mice O 0
were O 0
subjected O 0
to O 0
doxorubicin B-Chemical 0
treatment O 0
. O 0

Compared O 0
with O 0
wild O 0
- O 0
type O 0
mice O 0
, O 0
transgenic O 0
mice O 0
exhibited O 0
higher O 0
survival O 0
rate O 0
as O 0
well O 0
as O 0
more O 0
preserved O 0
left O 0
ventricular O 0
function O 0
and O 0
cardiac O 0
expression O 0
of O 0
alpha O 0
- O 0
sarcomeric O 0
actin O 0
. O 0

Doxorubicin B-Chemical 0
induced O 0
myocardial O 0
cell O 0
apoptosis O 0
in O 0
wild O 0
- O 0
type O 0
mice O 0
but O 0
not O 0
in O 0
transgenic O 0
mice O 0
. O 0

Expression O 0
of O 0
p300 O 0
increased O 0
the O 0
cardiac O 0
level O 0
of O 0
bcl O 0
- O 0
2 O 0
and O 0
mdm O 0
- O 0
2 O 0
, O 0
but O 0
not O 0
that O 0
of O 0
p53 O 0
or O 0
other O 0
members O 0
of O 0
the O 0
bcl O 0
- O 0
2 O 0
family O 0
. O 0

These O 0
findings O 0
demonstrate O 0
that O 0
overexpression O 0
of O 0
p300 O 0
protects O 0
cardiac O 0
myocytes O 0
from O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
apoptosis O 0
and O 0
reduces O 0
the O 0
extent O 0
of O 0
acute O 0
heart B-Disease 0
failure I-Disease 0
in O 0
adult O 0
mice O 0
in O 0
vivo O 0
. O 0

Methimazole B-Chemical 0
- O 0
induced O 0
cholestatic B-Disease 0
jaundice I-Disease 0
. O 0

Methimazole B-Chemical 0
is O 0
a O 0
widely O 0
used O 0
and O 0
generally O 0
well O 0
- O 0
tolerated O 0
antithyroid O 0
agent O 0
. O 0

A O 0
43 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
had O 0
severe O 0
jaundice B-Disease 0
and O 0
itching B-Disease 0
1 O 0
month O 0
after O 0
receiving O 0
methimazole B-Chemical 0
( O 0
10 O 0
mg O 0
tid O 0
) O 0
and O 0
propranolol B-Chemical 0
( O 0
20 O 0
mg O 0
tid O 0
) O 0
for O 0
treatment O 0
of O 0
hyperthyroidism B-Disease 0
. O 0

The O 0
patient O 0
continued O 0
treatment O 0
for O 0
another O 0
4 O 0
days O 0
after O 0
the O 0
appearance O 0
of O 0
jaundice B-Disease 0
until O 0
she O 0
finished O 0
both O 0
medications O 0
. O 0

When O 0
seen O 0
at O 0
the O 0
emergency O 0
department O 0
2 O 0
weeks O 0
later O 0
, O 0
she O 0
still O 0
had O 0
severe O 0
icterus B-Disease 0
, O 0
pruritus B-Disease 0
, O 0
and O 0
hyperbilirubinemia B-Disease 0
, O 0
formed O 0
mainly O 0
of O 0
the O 0
conjugated O 0
fraction O 0
. O 0

Methimazole B-Chemical 0
- O 0
induced O 0
cholestasis B-Disease 0
was O 0
diagnosed O 0
, O 0
and O 0
propranolol B-Chemical 0
therapy O 0
was O 0
resumed O 0
. O 0

Over O 0
the O 0
following O 0
9 O 0
days O 0
, O 0
the O 0
symptoms O 0
improved O 0
and O 0
plasma O 0
bilirubin B-Chemical 0
levels O 0
were O 0
normal O 0
after O 0
12 O 0
weeks O 0
without O 0
methimazole B-Chemical 0
. O 0

In O 0
rare O 0
cases O 0
within O 0
the O 0
first O 0
few O 0
weeks O 0
of O 0
therapy O 0
, O 0
this O 0
drug O 0
can O 0
cause O 0
severe O 0
and O 0
reversible O 0
cholestatic B-Disease 0
jaundice I-Disease 0
. O 0

Physicians O 0
and O 0
patients O 0
should O 0
be O 0
aware O 0
of O 0
this O 0
adverse O 0
effect O 0
so O 0
that O 0
, O 0
upon O 0
occurrence O 0
, O 0
they O 0
can O 0
discontinue O 0
methimazole B-Chemical 0
therapy O 0
and O 0
avoid O 0
unnecessary O 0
invasive O 0
procedures O 0
. O 0

Atrial B-Disease 0
fibrillation I-Disease 0
following O 0
chemotherapy O 0
for O 0
stage O 0
IIIE O 0
diffuse O 0
large O 0
B O 0
- O 0
cell O 0
gastric B-Disease 0
lymphoma I-Disease 0
in O 0
a O 0
patient O 0
with O 0
myotonic B-Disease 0
dystrophy I-Disease 0
( O 0
Steinert B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
) O 0
. O 0

The O 0
authors O 0
describe O 0
the O 0
unusual O 0
association O 0
between O 0
diffuse O 0
B O 0
- O 0
cell O 0
gastric B-Disease 0
lymphoma I-Disease 0
and O 0
myotonic B-Disease 0
dystrophy I-Disease 0
, O 0
the O 0
most O 0
common O 0
form O 0
of O 0
adult O 0
muscular B-Disease 0
dystrophy I-Disease 0
, O 0
and O 0
sudden O 0
atrial B-Disease 0
fibrillation I-Disease 0
following O 0
one O 0
cycle O 0
of O 0
doxorubicin B-Chemical 0
- O 0
based O 0
chemotherapy O 0
in O 0
the O 0
same O 0
patient O 0
. O 0

Atrial B-Disease 0
fibrillation I-Disease 0
or O 0
other O 0
cardiac B-Disease 0
arrhythmias I-Disease 0
are O 0
unusual O 0
complications O 0
in O 0
patients O 0
treated O 0
with O 0
chemotherapy O 0
. O 0

The O 0
cardiac B-Disease 0
toxicity I-Disease 0
intrinsically O 0
associated O 0
with O 0
the O 0
aggressive O 0
chemotherapy O 0
employed O 0
could O 0
function O 0
as O 0
a O 0
triggering O 0
factor O 0
for O 0
the O 0
arrhythmia B-Disease 0
in O 0
the O 0
predisposed O 0
myocardium O 0
of O 0
this O 0
patient O 0
. O 0

Hypersensitivity B-Disease 0
immune O 0
reaction O 0
as O 0
a O 0
mechanism O 0
for O 0
dilevalol B-Chemical 0
- O 0
associated O 0
hepatitis B-Disease 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
assess O 0
lymphocyte O 0
reactivity O 0
to O 0
dilevalol B-Chemical 0
and O 0
to O 0
serum O 0
containing O 0
putative O 0
ex O 0
vivo O 0
dilevalol B-Chemical 0
antigens O 0
or O 0
metabolites O 0
in O 0
a O 0
case O 0
of O 0
dilevalol B-Chemical 0
- O 0
induced O 0
liver B-Disease 0
injury I-Disease 0
. O 0

PATIENT O 0
: O 0
A O 0
58 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
a O 0
clinical O 0
diagnosis O 0
of O 0
dilevalol B-Chemical 0
- O 0
induced O 0
liver B-Disease 0
injury I-Disease 0
. O 0

METHODS O 0
: O 0
Peripheral O 0
blood O 0
mononuclear O 0
cells O 0
collected O 0
from O 0
the O 0
patient O 0
were O 0
cultured O 0
in O 0
the O 0
presence O 0
of O 0
a O 0
solution O 0
of O 0
dilevalol B-Chemical 0
and O 0
also O 0
with O 0
sera O 0
collected O 0
from O 0
a O 0
volunteer O 0
before O 0
and O 0
after O 0
dilevalol B-Chemical 0
intake O 0
. O 0

A O 0
similar O 0
protocol O 0
was O 0
performed O 0
with O 0
lymphocytes O 0
from O 0
a O 0
healthy O 0
subject O 0
. O 0

RESULTS O 0
: O 0
No O 0
lymphocyte O 0
proliferation O 0
was O 0
observed O 0
either O 0
in O 0
the O 0
patient O 0
or O 0
in O 0
the O 0
healthy O 0
volunteer O 0
in O 0
the O 0
presence O 0
of O 0
dilevalol B-Chemical 0
solutions O 0
. O 0

A O 0
significant O 0
proliferative O 0
response O 0
to O 0
serum O 0
collected O 0
after O 0
dilevalol B-Chemical 0
intake O 0
was O 0
observed O 0
in O 0
the O 0
case O 0
of O 0
the O 0
patient O 0
compared O 0
with O 0
the O 0
proliferative O 0
response O 0
to O 0
the O 0
serum O 0
collected O 0
before O 0
the O 0
drug O 0
intake O 0
. O 0

No O 0
reactivity O 0
was O 0
found O 0
when O 0
lymphocytes O 0
from O 0
the O 0
healthy O 0
subject O 0
were O 0
tested O 0
under O 0
similar O 0
conditions O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
methodology O 0
used O 0
allowed O 0
the O 0
detection O 0
of O 0
lymphocyte O 0
sensitization O 0
to O 0
sera O 0
containing O 0
ex O 0
vivo O 0
- O 0
prepared O 0
dilevalol B-Chemical 0
antigens O 0
, O 0
suggesting O 0
the O 0
involvement O 0
of O 0
an O 0
immunologic O 0
mechanism O 0
in O 0
dilevalol B-Chemical 0
- O 0
induced O 0
liver B-Disease 0
injury I-Disease 0
. O 0

Increased O 0
expression O 0
and O 0
apical O 0
targeting O 0
of O 0
renal O 0
ENaC O 0
subunits O 0
in O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
- O 0
induced O 0
nephrotic B-Disease 0
syndrome I-Disease 0
in O 0
rats O 0
. O 0

Nephrotic B-Disease 0
syndrome I-Disease 0
is O 0
often O 0
accompanied O 0
by O 0
sodium B-Chemical 0
retention O 0
and O 0
generalized O 0
edema B-Disease 0
. O 0

However O 0
, O 0
the O 0
molecular O 0
basis O 0
for O 0
the O 0
decreased O 0
renal O 0
sodium B-Chemical 0
excretion O 0
remains O 0
undefined O 0
. O 0

We O 0
hypothesized O 0
that O 0
epithelial O 0
Na B-Chemical 0
channel O 0
( O 0
ENaC O 0
) O 0
subunit O 0
dysregulation O 0
may O 0
be O 0
responsible O 0
for O 0
the O 0
increased O 0
sodium B-Chemical 0
retention O 0
. O 0

An O 0
experimental O 0
group O 0
of O 0
rats O 0
was O 0
treated O 0
with O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
( O 0
PAN B-Chemical 0
; O 0
180 O 0
mg O 0
/ O 0
kg O 0
iv O 0
) O 0
, O 0
whereas O 0
the O 0
control O 0
group O 0
received O 0
only O 0
vehicle O 0
. O 0

After O 0
7 O 0
days O 0
, O 0
PAN B-Chemical 0
treatment O 0
induced O 0
significant O 0
proteinuria B-Disease 0
, O 0
hypoalbuminemia B-Disease 0
, O 0
decreased O 0
urinary O 0
sodium B-Chemical 0
excretion O 0
, O 0
and O 0
extensive O 0
ascites B-Disease 0
. O 0

The O 0
protein O 0
abundance O 0
of O 0
alpha O 0
- O 0
ENaC O 0
and O 0
beta O 0
- O 0
ENaC O 0
was O 0
increased O 0
in O 0
the O 0
inner O 0
stripe O 0
of O 0
the O 0
outer O 0
medulla O 0
( O 0
ISOM O 0
) O 0
and O 0
in O 0
the O 0
inner O 0
medulla O 0
( O 0
IM O 0
) O 0
but O 0
was O 0
not O 0
altered O 0
in O 0
the O 0
cortex O 0
. O 0

gamma O 0
- O 0
ENaC O 0
abundance O 0
was O 0
increased O 0
in O 0
the O 0
cortex O 0
, O 0
ISOM O 0
, O 0
and O 0
IM O 0
. O 0

Immunoperoxidase O 0
brightfield O 0
- O 0
and O 0
laser O 0
- O 0
scanning O 0
confocal O 0
fluorescence O 0
microscopy O 0
demonstrated O 0
increased O 0
targeting O 0
of O 0
alpha O 0
- O 0
ENaC O 0
, O 0
beta O 0
- O 0
ENaC O 0
, O 0
and O 0
gamma O 0
- O 0
ENaC O 0
subunits O 0
to O 0
the O 0
apical O 0
plasma O 0
membrane O 0
in O 0
the O 0
distal O 0
convoluted O 0
tubule O 0
( O 0
DCT2 O 0
) O 0
, O 0
connecting O 0
tubule O 0
, O 0
and O 0
cortical O 0
and O 0
medullary O 0
collecting O 0
duct O 0
segments O 0
. O 0

Immunoelectron O 0
microscopy O 0
further O 0
revealed O 0
an O 0
increased O 0
labeling O 0
of O 0
alpha O 0
- O 0
ENaC O 0
in O 0
the O 0
apical O 0
plasma O 0
membrane O 0
of O 0
cortical O 0
collecting O 0
duct O 0
principal O 0
cells O 0
of O 0
PAN B-Chemical 0
- O 0
treated O 0
rats O 0
, O 0
indicating O 0
enhanced O 0
apical O 0
targeting O 0
of O 0
alpha O 0
- O 0
ENaC O 0
subunits O 0
. O 0

In O 0
contrast O 0
, O 0
the O 0
protein O 0
abundances O 0
of O 0
Na B-Chemical 0
( O 0
+ O 0
) O 0
/ O 0
H B-Chemical 0
( O 0
+ O 0
) O 0
exchanger O 0
type O 0
3 O 0
( O 0
NHE3 O 0
) O 0
, 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
2Cl B-Chemical 0
( O 0
- O 0
) O 0
cotransporter O 0
( O 0
BSC O 0
- O 0
1 O 0
) O 0
, O 0
and O 0
thiazide B-Chemical 0
- O 0
sensitive O 0
Na B-Chemical 0
( O 0
+ O 0
) O 0
- O 0
Cl B-Chemical 0
( O 0
- O 0
) O 0
cotransporter O 0
( O 0
TSC O 0
) O 0
were O 0
decreased O 0
. O 0

Moreover O 0
, O 0
the O 0
abundance O 0
of O 0
the O 0
alpha O 0
( O 0
1 O 0
) O 0
- O 0
subunit O 0
of O 0
the O 0
Na B-Chemical 0
- O 0
K B-Chemical 0
- O 0
ATPase O 0
was O 0
decreased O 0
in O 0
the O 0
cortex O 0
and O 0
ISOM O 0
, O 0
but O 0
it O 0
remained O 0
unchanged O 0
in O 0
the O 0
IM O 0
. O 0

In O 0
conclusion O 0
, O 0
the O 0
increased O 0
or O 0
sustained O 0
expression O 0
of O 0
ENaC O 0
subunits O 0
combined O 0
with O 0
increased O 0
apical O 0
targeting O 0
in O 0
the O 0
DCT2 O 0
, O 0
connecting O 0
tubule O 0
, O 0
and O 0
collecting O 0
duct O 0
are O 0
likely O 0
to O 0
play O 0
a O 0
role O 0
in O 0
the O 0
sodium B-Chemical 0
retention O 0
associated O 0
with O 0
PAN B-Chemical 0
- O 0
induced O 0
nephrotic B-Disease 0
syndrome I-Disease 0
. O 0

The O 0
decreased O 0
abundance O 0
of O 0
NHE3 O 0
, O 0
BSC O 0
- O 0
1 O 0
, O 0
TSC O 0
, O 0
and O 0
Na B-Chemical 0
- O 0
K B-Chemical 0
- O 0
ATPase O 0
may O 0
play O 0
a O 0
compensatory O 0
role O 0
to O 0
promote O 0
sodium B-Chemical 0
excretion O 0
. O 0

Pallidal O 0
stimulation O 0
: O 0
an O 0
alternative O 0
to O 0
pallidotomy O 0
? O 0

A O 0
resurgence O 0
of O 0
interest O 0
in O 0
the O 0
surgical O 0
treatment O 0
of 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
came O 0
with O 0
the O 0
rediscovery O 0
of O 0
posteroventral O 0
pallidotomy O 0
by O 0
Laitinen O 0
in O 0
1985 O 0
. O 0

Laitinen O 0
' O 0
s O 0
procedure O 0
improved O 0
most O 0
symptoms O 0
in O 0
drug O 0
- O 0
resistant O 0
PD B-Disease 0
, O 0
which O 0
engendered O 0
wide O 0
interest O 0
in O 0
the O 0
neurosurgical O 0
community O 0
. O 0

Another O 0
lesioning O 0
procedure O 0
, O 0
ventrolateral O 0
thalamotomy O 0
, O 0
has O 0
become O 0
a O 0
powerful O 0
alternative O 0
to O 0
stimulate O 0
the O 0
nucleus O 0
ventralis O 0
intermedius O 0
, O 0
producing O 0
high O 0
long O 0
- O 0
term O 0
success O 0
rates O 0
and O 0
low O 0
morbidity O 0
rates O 0
. O 0

Pallidal O 0
stimulation O 0
has O 0
not O 0
met O 0
with O 0
the O 0
same O 0
success O 0
. O 0

According O 0
to O 0
the O 0
literature O 0
pallidotomy O 0
improves O 0
the O 0
" O 0
on O 0
" O 0
symptoms O 0
of O 0
PD B-Disease 0
, O 0
such O 0
as O 0
dyskinesias B-Disease 0
, O 0
as O 0
well O 0
as O 0
the O 0
" O 0
off O 0
" O 0
symptoms O 0
, O 0
such O 0
as O 0
rigidity B-Disease 0
, O 0
bradykinesia B-Disease 0
, O 0
and O 0
on O 0
- O 0
off O 0
fluctuations O 0
. O 0

Pallidal O 0
stimulation O 0
improves O 0
bradykinesia B-Disease 0
and O 0
rigidity B-Disease 0
to O 0
a O 0
minor O 0
extent O 0
; O 0
however O 0
, O 0
its O 0
strength O 0
seems O 0
to O 0
be O 0
in O 0
improving O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
. O 0

Stimulation O 0
often O 0
produces O 0
an O 0
improvement O 0
in O 0
the O 0
hyper B-Disease 0
- I-Disease 0
or I-Disease 0
dyskinetic I-Disease 0
upper O 0
limbs O 0
, O 0
but O 0
increases O 0
the O 0
" O 0
freezing O 0
" O 0
phenomenon O 0
in O 0
the O 0
lower O 0
limbs O 0
at O 0
the O 0
same O 0
time O 0
. O 0

Considering O 0
the O 0
small O 0
increase O 0
in O 0
the O 0
patient O 0
' O 0
s O 0
independence O 0
, O 0
the O 0
high O 0
costs O 0
of O 0
bilateral O 0
implants O 0
, O 0
and O 0
the O 0
difficulty O 0
most O 0
patients O 0
experience O 0
in O 0
handling O 0
the O 0
devices O 0
, O 0
the O 0
question O 0
arises O 0
as O 0
to O 0
whether O 0
bilateral O 0
pallidal O 0
stimulation O 0
is O 0
a O 0
real O 0
alternative O 0
to O 0
pallidotomy O 0
. O 0

Effects O 0
of O 0
the O 0
cyclooxygenase O 0
- O 0
2 O 0
specific O 0
inhibitor O 0
valdecoxib B-Chemical 0
versus O 0
nonsteroidal O 0
antiinflammatory O 0
agents O 0
and O 0
placebo O 0
on O 0
cardiovascular O 0
thrombotic B-Disease 0
events O 0
in O 0
patients O 0
with O 0
arthritis B-Disease 0
. O 0

There O 0
have O 0
been O 0
concerns O 0
that O 0
the O 0
risk O 0
of O 0
cardiovascular O 0
thrombotic B-Disease 0
events O 0
may O 0
be O 0
higher O 0
with O 0
cyclooxygenase O 0
( O 0
COX O 0
) O 0
- O 0
2 O 0
- O 0
specific O 0
inhibitors O 0
than O 0
nonselective O 0
nonsteroidal O 0
antiinflammatory O 0
drugs O 0
( O 0
NSAIDs O 0
) O 0
. O 0

We O 0
evaluated O 0
cardiovascular O 0
event O 0
data O 0
for O 0
valdecoxib B-Chemical 0
, O 0
a O 0
new O 0
COX O 0
- O 0
2 O 0
- O 0
specific O 0
inhibitor O 0
in O 0
approximately O 0
8000 O 0
patients O 0
with O 0
osteoarthritis B-Disease 0
and O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
treated O 0
with O 0
this O 0
agent O 0
in O 0
randomized O 0
clinical O 0
trials O 0
. O 0

The O 0
incidence O 0
of O 0
cardiovascular O 0
thrombotic B-Disease 0
events O 0
( O 0
cardiac O 0
, O 0
cerebrovascular O 0
and O 0
peripheral O 0
vascular O 0
, O 0
or O 0
arterial O 0
thrombotic B-Disease 0
) O 0
was O 0
determined O 0
by O 0
analyzing O 0
pooled O 0
valdecoxib B-Chemical 0
( O 0
10 O 0
- O 0
80 O 0
mg O 0
daily O 0
) O 0
, O 0
nonselective O 0
NSAID O 0
( O 0
diclofenac B-Chemical 0
75 O 0
mg O 0
bid O 0
, O 0
ibuprofen B-Chemical 0
800 O 0
mg O 0
tid O 0
, O 0
or O 0
naproxen B-Chemical 0
500 O 0
mg O 0
bid O 0
) O 0
and O 0
placebo O 0
data O 0
from O 0
10 O 0
randomized O 0
osteoarthritis B-Disease 0
and O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
trials O 0
that O 0
were O 0
6 O 0
- O 0
52 O 0
weeks O 0
in O 0
duration O 0
. O 0

The O 0
incidence O 0
rates O 0
of O 0
events O 0
were O 0
determined O 0
in O 0
all O 0
patients O 0
( O 0
n O 0
= O 0
7934 O 0
) O 0
and O 0
in O 0
users O 0
of O 0
low O 0
- O 0
dose O 0
( O 0
< O 0
or O 0
= O 0
325 O 0
mg O 0
daily O 0
) O 0
aspirin B-Chemical 0
( O 0
n O 0
= O 0
1051 O 0
) O 0
and O 0
nonusers O 0
of O 0
aspirin B-Chemical 0
( O 0
n O 0
= O 0
6883 O 0
) O 0
. O 0

Crude O 0
and O 0
exposure O 0
- O 0
adjusted O 0
incidences O 0
of O 0
thrombotic B-Disease 0
events O 0
were O 0
similar O 0
for O 0
valdecoxib B-Chemical 0
, O 0
NSAIDs O 0
, O 0
and O 0
placebo O 0
. O 0

The O 0
risk O 0
of O 0
serious O 0
thrombotic B-Disease 0
events O 0
was O 0
also O 0
similar O 0
for O 0
each O 0
valdecoxib B-Chemical 0
dose O 0
. O 0

Thrombotic B-Disease 0
risk O 0
was O 0
consistently O 0
higher O 0
for O 0
users O 0
of O 0
aspirin B-Chemical 0
users O 0
than O 0
nonusers O 0
of O 0
aspirin B-Chemical 0
( O 0
placebo O 0
, O 0
1 O 0
. O 0
4 O 0
% O 0
vs O 0
. O 0
0 O 0
% O 0
; O 0
valdecoxib B-Chemical 0
, O 0
1 O 0
. O 0
7 O 0
% O 0
vs O 0
. O 0
0 O 0
. O 0
2 O 0
% O 0
; O 0
NSAIDs O 0
, O 0
1 O 0
. O 0
9 O 0
% O 0
vs O 0
. O 0
0 O 0
. O 0
5 O 0
% O 0
) O 0
. O 0

The O 0
rates O 0
of O 0
events O 0
in O 0
users O 0
of O 0
aspirin B-Chemical 0
were O 0
similar O 0
for O 0
all O 0
3 O 0
treatment O 0
groups O 0
and O 0
across O 0
valdecoxib B-Chemical 0
doses O 0
. O 0

Short O 0
- O 0
and O 0
intermediate O 0
- O 0
term O 0
treatment O 0
with O 0
therapeutic O 0
( O 0
10 O 0
or O 0
20 O 0
mg O 0
daily O 0
) O 0
and O 0
supratherapeutic O 0
( O 0
40 O 0
or O 0
80 O 0
mg O 0
daily O 0
) O 0
valdecoxib B-Chemical 0
doses O 0
was O 0
not O 0
associated O 0
with O 0
an O 0
increased O 0
incidence O 0
of O 0
thrombotic B-Disease 0
events O 0
relative O 0
to O 0
nonselective O 0
NSAIDs O 0
or O 0
placebo O 0
in O 0
osteoarthritis B-Disease 0
and O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
patients O 0
in O 0
controlled O 0
clinical O 0
trials O 0
. O 0

Hypersensitivity B-Disease 0
myocarditis B-Disease 0
complicating O 0
hypertrophic B-Disease 0
cardiomyopathy I-Disease 0
heart O 0
. O 0

The O 0
present O 0
report O 0
describes O 0
a O 0
case O 0
of O 0
eosinophilic B-Disease 0
myocarditis I-Disease 0
complicating O 0
hypertrophic B-Disease 0
cardiomyopathy I-Disease 0
. O 0

The O 0
47 O 0
- O 0
year O 0
- O 0
old O 0
female O 0
patient O 0
, O 0
known O 0
to O 0
have O 0
hypertrophic B-Disease 0
cardiomyopathy I-Disease 0
, O 0
was O 0
admitted O 0
with O 0
biventricular B-Disease 0
failure I-Disease 0
and O 0
managed O 0
aggressively O 0
with O 0
dobutamine B-Chemical 0
infusion O 0
and O 0
other O 0
drugs O 0
while O 0
being O 0
assessed O 0
for O 0
heart O 0
transplantation O 0
. O 0

On O 0
transthoracic O 0
echocardiogram O 0
, O 0
she O 0
had O 0
moderate O 0
left B-Disease 0
ventricular I-Disease 0
dysfunction I-Disease 0
with O 0
regional O 0
variability O 0
and O 0
moderate O 0
mitral B-Disease 0
regurgitation I-Disease 0
. O 0

The O 0
recipient O 0
' O 0
s O 0
heart O 0
showed O 0
the O 0
features O 0
of O 0
apical O 0
hypertrophic B-Disease 0
cardiomyopathy I-Disease 0
and O 0
myocarditis B-Disease 0
with O 0
abundant O 0
eosinophils O 0
. O 0

Myocarditis B-Disease 0
is O 0
rare O 0
and O 0
eosinophilic B-Disease 0
myocarditis I-Disease 0
is O 0
rarer O 0
. O 0

It O 0
is O 0
likely O 0
that O 0
the O 0
hypersensitivity B-Disease 0
( O 0
eosinophilic B-Disease 0
) O 0
myocarditis B-Disease 0
was O 0
related O 0
to O 0
dobutamine B-Chemical 0
infusion O 0
therapy O 0
. O 0

Eosinophilic B-Disease 0
myocarditis I-Disease 0
has O 0
been O 0
reported O 0
with O 0
an O 0
incidence O 0
of O 0
2 O 0
. O 0
4 O 0
% O 0
to O 0
7 O 0
. O 0
2 O 0
% O 0
in O 0
explanted O 0
hearts O 0
and O 0
may O 0
be O 0
related O 0
to O 0
multidrug O 0
therapy O 0
. O 0

Time O 0
trends O 0
in O 0
warfarin B-Chemical 0
- O 0
associated O 0
hemorrhage B-Disease 0
. O 0

The O 0
annual O 0
incidence O 0
of O 0
warfarin B-Chemical 0
- O 0
related O 0
bleeding B-Disease 0
at O 0
Brigham O 0
and O 0
Women O 0
' O 0
s O 0
Hospital O 0
increased O 0
from O 0
0 O 0
. O 0
97 O 0
/ O 0
1 O 0
, O 0
000 O 0
patient O 0
admissions O 0
in O 0
the O 0
first O 0
time O 0
period O 0
( O 0
January O 0
1995 O 0
to O 0
October O 0
1998 O 0
) O 0
to O 0
1 O 0
. O 0
19 O 0
/ O 0
1 O 0
, O 0
000 O 0
patient O 0
admissions O 0
in O 0
the O 0
second O 0
time O 0
period O 0
( O 0
November O 0
1998 O 0
to O 0
August O 0
2002 O 0
) O 0
of O 0
this O 0
study O 0
. O 0

The O 0
proportion O 0
of O 0
patients O 0
with O 0
major O 0
and O 0
intracranial B-Disease 0
bleeding I-Disease 0
increased O 0
from O 0
20 O 0
. O 0
2 O 0
% O 0
and O 0
1 O 0
. O 0
9 O 0
% O 0
, O 0
respectively O 0
, O 0
in O 0
the O 0
first O 0
time O 0
period O 0
, O 0
to O 0
33 O 0
. O 0
3 O 0
% O 0
and O 0
7 O 0
. O 0
8 O 0
% O 0
, O 0
respectively O 0
, O 0
in O 0
the O 0
second O 0
. O 0

Yohimbine B-Chemical 0
treatment O 0
of O 0
sexual B-Disease 0
side I-Disease 0
effects I-Disease 0
induced O 0
by O 0
serotonin B-Chemical 0
reuptake O 0
blockers O 0
. O 0

BACKGROUND O 0
: O 0
Preclinical O 0
and O 0
clinical O 0
studies O 0
suggest O 0
that O 0
yohimbine B-Chemical 0
facilitates O 0
sexual O 0
behavior O 0
and O 0
may O 0
be O 0
helpful O 0
in O 0
the O 0
treatment O 0
of O 0
male B-Disease 0
impotence I-Disease 0
. O 0

A O 0
single O 0
case O 0
report O 0
suggests O 0
that O 0
yohimbine B-Chemical 0
may O 0
be O 0
used O 0
to O 0
treat O 0
the O 0
sexual B-Disease 0
side I-Disease 0
effects I-Disease 0
of O 0
clomipramine B-Chemical 0
. O 0

This O 0
study O 0
evaluated O 0
yohimbine B-Chemical 0
as O 0
a O 0
treatment O 0
for O 0
the O 0
sexual B-Disease 0
side I-Disease 0
effects I-Disease 0
caused O 0
by O 0
serotonin B-Chemical 0
reuptake O 0
blockers O 0
. O 0

METHOD O 0
: O 0
Six O 0
patients O 0
with O 0
either O 0
obsessive B-Disease 0
compulsive I-Disease 0
disorder I-Disease 0
, O 0
trichotillomania B-Disease 0
, O 0
anxiety B-Disease 0
, O 0
or O 0
affective B-Disease 0
disorders I-Disease 0
who O 0
suffered O 0
sexual B-Disease 0
side I-Disease 0
effects I-Disease 0
after O 0
treatment O 0
with O 0
serotonin B-Chemical 0
reuptake O 0
blockers O 0
were O 0
given O 0
yohimbine B-Chemical 0
on O 0
a O 0
p O 0
. O 0
r O 0
. O 0
n O 0
. O 0
basis O 0
in O 0
an O 0
open O 0
clinical O 0
trial O 0
. O 0

Various O 0
doses O 0
of O 0
yohimbine B-Chemical 0
were O 0
used O 0
to O 0
determine O 0
the O 0
ideal O 0
dose O 0
for O 0
each O 0
patient O 0
. O 0

RESULTS O 0
: O 0
Five O 0
of O 0
the O 0
six O 0
patients O 0
experienced O 0
improved O 0
sexual O 0
functioning O 0
after O 0
taking O 0
yohimbine B-Chemical 0
. O 0

One O 0
patient O 0
who O 0
failed O 0
to O 0
comply O 0
with O 0
yohimbine B-Chemical 0
treatment O 0
had O 0
no O 0
therapeutic O 0
effects O 0
. O 0

Side O 0
effects O 0
of O 0
yohimbine B-Chemical 0
included O 0
excessive O 0
sweating O 0
, O 0
increased O 0
anxiety B-Disease 0
, O 0
and O 0
a O 0
wound O 0
- O 0
up O 0
feeling O 0
in O 0
some O 0
patients O 0
. O 0

CONCLUSION 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
yohimbine B-Chemical 0
may O 0
be O 0
an O 0
effective O 0
treatment O 0
for O 0
the O 0
sexual B-Disease 0
side I-Disease 0
effects I-Disease 0
caused O 0
by O 0
serotonin B-Chemical 0
reuptake O 0
blockers O 0
. O 0

Future O 0
controlled O 0
studies O 0
are O 0
needed O 0
to O 0
further O 0
investigate O 0
the O 0
effectiveness O 0
and O 0
safety O 0
of O 0
yohimbine B-Chemical 0
for O 0
this O 0
indication O 0
. O 0

Hemorrhagic B-Disease 0
cystitis I-Disease 0
complicating O 0
bone O 0
marrow O 0
transplantation O 0
. O 0

Hemorrhagic B-Disease 0
cystitis I-Disease 0
is O 0
a O 0
potentially O 0
serious O 0
complication O 0
of O 0
high O 0
- O 0
dose O 0
cyclophosphamide B-Chemical 0
therapy O 0
administered O 0
before O 0
bone O 0
marrow O 0
transplantation O 0
. O 0

As O 0
standard O 0
practice O 0
at O 0
our O 0
institution O 0
, O 0
patients O 0
who O 0
are O 0
scheduled O 0
to O 0
receive O 0
a O 0
bone O 0
marrow O 0
transplant O 0
are O 0
treated O 0
prophylactically O 0
with O 0
forced O 0
hydration O 0
and O 0
bladder O 0
irrigation O 0
. O 0

In O 0
an O 0
attempt O 0
to O 0
obviate O 0
the O 0
inconvenience O 0
of O 0
bladder O 0
irrigation O 0
, O 0
we O 0
conducted O 0
a O 0
feasibility O 0
trial O 0
of O 0
uroprophylaxis O 0
with O 0
mesna B-Chemical 0
, O 0
which O 0
neutralizes O 0
the O 0
hepatic O 0
metabolite O 0
of O 0
cyclophosphamide B-Chemical 0
that O 0
causes O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
. O 0

Of O 0
97 O 0
patients O 0
who O 0
received O 0
standard O 0
prophylaxis O 0
, O 0
4 O 0
had O 0
symptomatic O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
. O 0

In O 0
contrast O 0
, O 0
two O 0
of O 0
four O 0
consecutive O 0
patients O 0
who O 0
received O 0
mesna B-Chemical 0
uroprophylaxis O 0
before O 0
allogeneic O 0
bone O 0
marrow O 0
transplantation O 0
had O 0
severe O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
for O 0
at O 0
least O 0
2 O 0
weeks O 0
. O 0

Because O 0
of O 0
this O 0
suboptimal O 0
result O 0
, O 0
we O 0
resumed O 0
the O 0
use O 0
of O 0
bladder O 0
irrigation O 0
and O 0
forced O 0
hydration O 0
to O 0
minimize O 0
the O 0
risk O 0
of O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
. O 0

Consensus O 0
statement O 0
concerning O 0
cardiotoxicity B-Disease 0
occurring O 0
during O 0
haematopoietic O 0
stem O 0
cell O 0
transplantation O 0
in O 0
the O 0
treatment O 0
of O 0
autoimmune B-Disease 0
diseases I-Disease 0
, O 0
with O 0
special O 0
reference O 0
to O 0
systemic B-Disease 0
sclerosis I-Disease 0
and O 0
multiple B-Disease 0
sclerosis I-Disease 0
. O 0

Autologous O 0
haematopoietic O 0
stem O 0
cell O 0
transplantation O 0
is O 0
now O 0
a O 0
feasible O 0
and O 0
effective O 0
treatment O 0
for O 0
selected O 0
patients O 0
with O 0
severe O 0
autoimmune B-Disease 0
diseases I-Disease 0
. O 0

Worldwide O 0
, O 0
over O 0
650 O 0
patients O 0
have O 0
been O 0
transplanted O 0
in O 0
the O 0
context O 0
of O 0
phase O 0
I O 0
and O 0
II O 0
clinical O 0
trials O 0
. O 0

The O 0
results O 0
are O 0
encouraging O 0
enough O 0
to O 0
begin O 0
randomised O 0
phase O 0
III O 0
trials O 0
. O 0

However O 0
, O 0
as O 0
predicted O 0
, O 0
significant O 0
transplant O 0
- O 0
related O 0
morbidity O 0
and O 0
mortality O 0
have O 0
been O 0
observed O 0
. O 0

This O 0
is O 0
primarily O 0
due O 0
to O 0
complications O 0
related O 0
to O 0
either O 0
the O 0
stage O 0
of O 0
the O 0
disease O 0
at O 0
transplant O 0
or O 0
due O 0
to O 0
infections B-Disease 0
. O 0

The O 0
number O 0
of O 0
deaths O 0
related O 0
to O 0
cardiac B-Disease 0
toxicity I-Disease 0
is O 0
low O 0
. O 0

However O 0
, O 0
caution O 0
is O 0
required O 0
when O 0
cyclophosphamide B-Chemical 0
or O 0
anthracyclines B-Chemical 0
such O 0
as O 0
mitoxantrone B-Chemical 0
are O 0
used O 0
in O 0
patients O 0
with O 0
a O 0
possible O 0
underlying O 0
heart B-Disease 0
damage I-Disease 0
, O 0
for O 0
example O 0
, O 0
systemic B-Disease 0
sclerosis I-Disease 0
patients O 0
. O 0

In O 0
November O 0
2002 O 0
, O 0
a O 0
meeting O 0
was O 0
held O 0
in O 0
Florence O 0
, O 0
bringing O 0
together O 0
a O 0
number O 0
of O 0
experts O 0
in O 0
various O 0
fields O 0
, O 0
including O 0
rheumatology O 0
, O 0
cardiology O 0
, O 0
neurology O 0
, O 0
pharmacology O 0
and O 0
transplantation O 0
medicine O 0
. O 0

The O 0
object O 0
of O 0
the O 0
meeting O 0
was O 0
to O 0
analyse O 0
existing O 0
data O 0
, O 0
both O 0
published O 0
or O 0
available O 0
, O 0
in O 0
the O 0
European O 0
Group O 0
for O 0
Blood O 0
and O 0
Marrow O 0
Transplantation O 0
autoimmune B-Disease 0
disease I-Disease 0
database O 0
, O 0
and O 0
to O 0
propose O 0
a O 0
safe O 0
approach O 0
to O 0
such O 0
patients O 0
. O 0

A O 0
full O 0
cardiological O 0
assessment O 0
before O 0
and O 0
during O 0
the O 0
transplant O 0
emerged O 0
as O 0
the O 0
major O 0
recommendation O 0
. O 0

Does O 0
supplemental O 0
vitamin B-Chemical 0
C I-Chemical 0
increase O 0
cardiovascular B-Disease 0
disease I-Disease 0
risk O 0
in O 0
women O 0
with O 0
diabetes B-Disease 0
? O 0

BACKGROUND O 0
: O 0
Vitamin B-Chemical 0
C I-Chemical 0
acts O 0
as O 0
a O 0
potent O 0
antioxidant O 0
; O 0
however O 0
, O 0
it O 0
can O 0
also O 0
be O 0
a O 0
prooxidant O 0
and O 0
glycate O 0
protein O 0
under O 0
certain O 0
circumstances O 0
in O 0
vitro O 0
. O 0

These O 0
observations O 0
led O 0
us O 0
to O 0
hypothesize O 0
that O 0
a O 0
high O 0
intake O 0
of O 0
vitamin B-Chemical 0
C I-Chemical 0
in O 0
diabetic B-Disease 0
persons O 0
might O 0
promote O 0
atherosclerosis B-Disease 0
. O 0

OBJECTIVE O 0
: O 0
The O 0
objective O 0
was O 0
to O 0
examine O 0
the O 0
relation O 0
between O 0
vitamin B-Chemical 0
C I-Chemical 0
intake O 0
and O 0
mortality O 0
from O 0
cardiovascular B-Disease 0
disease I-Disease 0
. O 0

DESIGN O 0
: O 0
We O 0
studied O 0
the O 0
relation O 0
between O 0
vitamin B-Chemical 0
C I-Chemical 0
intake O 0
and O 0
mortality O 0
from O 0
total O 0
cardiovascular B-Disease 0
disease I-Disease 0
( O 0
n O 0
= O 0
281 O 0
) O 0
, O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
( O 0
n O 0
= O 0
175 O 0
) O 0
, O 0
and O 0
stroke B-Disease 0
( O 0
n O 0
= O 0
57 O 0
) O 0
in O 0
1923 O 0
postmenopausal O 0
women O 0
who O 0
reported O 0
being O 0
diabetic B-Disease 0
at O 0
baseline O 0
. O 0

Diet O 0
was O 0
assessed O 0
with O 0
a O 0
food O 0
- O 0
frequency O 0
questionnaire O 0
at O 0
baseline O 0
, O 0
and O 0
subjects O 0
initially O 0
free O 0
of O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
were O 0
prospectively O 0
followed O 0
for O 0
15 O 0
y O 0
. O 0

RESULTS O 0
: O 0
After O 0
adjustment O 0
for O 0
cardiovascular B-Disease 0
disease I-Disease 0
risk O 0
factors O 0
, O 0
type O 0
of O 0
diabetes B-Disease 0
medication O 0
used O 0
, O 0
duration O 0
of O 0
diabetes B-Disease 0
, O 0
and O 0
intakes O 0
of O 0
folate B-Chemical 0
, O 0
vitamin B-Chemical 0
E I-Chemical 0
, O 0
and O 0
beta B-Chemical 0
- I-Chemical 0
carotene I-Chemical 0
, O 0
the O 0
adjusted O 0
relative O 0
risks O 0
of O 0
total O 0
cardiovascular B-Disease 0
disease I-Disease 0
mortality O 0
were O 0
1 O 0
. O 0
0 O 0
, O 0
0 O 0
. O 0
97 O 0
, O 0
1 O 0
. O 0
11 O 0
, O 0
1 O 0
. O 0
47 O 0
, O 0
and O 0
1 O 0
. O 0
84 O 0
( O 0
P O 0
for O 0
trend O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
across O 0
quintiles O 0
of O 0
total O 0
vitamin B-Chemical 0
C I-Chemical 0
intake O 0
from O 0
food O 0
and O 0
supplements O 0
. O 0

Adjusted O 0
relative O 0
risks O 0
of O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
were O 0
1 O 0
. O 0
0 O 0
, O 0
0 O 0
. O 0
81 O 0
, O 0
0 O 0
. O 0
99 O 0
, O 0
1 O 0
. O 0
26 O 0
, O 0
and O 0
1 O 0
. O 0
91 O 0
( O 0
P O 0
for O 0
trend O 0
= O 0
0 O 0
. O 0
01 O 0
) O 0
and O 0
of O 0
stroke B-Disease 0
were O 0
1 O 0
. O 0
0 O 0
, O 0
0 O 0
. O 0
52 O 0
, O 0
1 O 0
. O 0
23 O 0
, O 0
2 O 0
. O 0
22 O 0
, O 0
and O 0
2 O 0
. O 0
57 O 0
( O 0
P O 0
for O 0
trend O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

When O 0
dietary O 0
and O 0
supplemental O 0
vitamin B-Chemical 0
C I-Chemical 0
were O 0
analyzed O 0
separately O 0
, O 0
only O 0
supplemental O 0
vitamin B-Chemical 0
C I-Chemical 0
showed O 0
a O 0
positive O 0
association O 0
with O 0
mortality O 0
endpoints O 0
. O 0

Vitamin B-Chemical 0
C I-Chemical 0
intake O 0
was O 0
unrelated O 0
to O 0
mortality O 0
from O 0
cardiovascular B-Disease 0
disease I-Disease 0
in O 0
the O 0
nondiabetic O 0
subjects O 0
at O 0
baseline O 0
. O 0

CONCLUSION O 0
: O 0
A O 0
high O 0
vitamin B-Chemical 0
C I-Chemical 0
intake O 0
from O 0
supplements O 0
is O 0
associated O 0
with O 0
an O 0
increased O 0
risk O 0
of O 0
cardiovascular B-Disease 0
disease I-Disease 0
mortality O 0
in O 0
postmenopausal O 0
women O 0
with O 0
diabetes B-Disease 0
. O 0

Optical O 0
coherence O 0
tomography O 0
can O 0
measure O 0
axonal O 0
loss O 0
in O 0
patients O 0
with O 0
ethambutol B-Chemical 0
- O 0
induced O 0
optic B-Disease 0
neuropathy I-Disease 0
. O 0

PURPOSE O 0
: O 0
To O 0
map O 0
and O 0
identify O 0
the O 0
pattern O 0
, O 0
in O 0
vivo O 0
, O 0
of O 0
axonal B-Disease 0
degeneration I-Disease 0
in O 0
ethambutol B-Chemical 0
- O 0
induced O 0
optic B-Disease 0
neuropathy I-Disease 0
using O 0
optical O 0
coherence O 0
tomography O 0
( O 0
OCT O 0
) O 0
. O 0

Ethambutol B-Chemical 0
is O 0
an O 0
antimycobacterial O 0
agent O 0
often O 0
used O 0
to O 0
treat O 0
tuberculosis B-Disease 0
. O 0

A O 0
serious O 0
complication O 0
of O 0
ethambutol B-Chemical 0
is O 0
an O 0
optic B-Disease 0
neuropathy I-Disease 0
that O 0
impairs O 0
visual O 0
acuity O 0
, O 0
contrast O 0
sensitivity O 0
, O 0
and O 0
color O 0
vision O 0
. O 0

However O 0
, O 0
early O 0
on O 0
, O 0
when O 0
the O 0
toxic O 0
optic B-Disease 0
neuropathy I-Disease 0
is O 0
mild O 0
and O 0
partly O 0
reversible O 0
, O 0
the O 0
funduscopic O 0
findings O 0
are O 0
often O 0
subtle O 0
and O 0
easy O 0
to O 0
miss O 0
. O 0

METHODS O 0
: O 0
Three O 0
subjects O 0
with O 0
a O 0
history O 0
of O 0
ethambutol B-Chemical 0
( O 0
EMB B-Chemical 0
) O 0
- O 0
induced O 0
optic B-Disease 0
neuropathy I-Disease 0
of O 0
short O 0
- O 0
, O 0
intermediate O 0
- O 0
, O 0
and O 0
long O 0
- O 0
term O 0
visual B-Disease 0
deficits I-Disease 0
were O 0
administered O 0
a O 0
full O 0
neuro O 0
- O 0
ophthalmologic O 0
examination O 0
including O 0
visual O 0
acuity O 0
, O 0
color O 0
vision O 0
, O 0
contrast O 0
sensitivity O 0
, O 0
and O 0
fundus O 0
examination O 0
. O 0

In O 0
addition O 0
, O 0
OCT O 0
( O 0
OCT O 0
3000 O 0
, O 0
Humphrey O 0
- O 0
Zeiss O 0
, O 0
Dublin O 0
, O 0
CA O 0
) O 0
was O 0
performed O 0
on O 0
both O 0
eyes O 0
of O 0
each O 0
subject O 0
using O 0
the O 0
retinal O 0
nerve O 0
fiber O 0
layer O 0
( O 0
RNFL O 0
) O 0
analysis O 0
protocol O 0
. O 0

OCT O 0
interpolates O 0
data O 0
from O 0
100 O 0
points O 0
around O 0
the O 0
optic O 0
nerve O 0
to O 0
effectively O 0
map O 0
out O 0
the O 0
RNFL O 0
. O 0

RESULTS O 0
: O 0
The O 0
results O 0
were O 0
compared O 0
to O 0
the O 0
calculated O 0
average O 0
RNFL O 0
of O 0
normal O 0
eyes O 0
accumulated O 0
from O 0
four O 0
prior O 0
studies O 0
using O 0
OCT O 0
, O 0
n O 0
= O 0
661 O 0
. O 0

In O 0
all O 0
subjects O 0
with O 0
history O 0
of O 0
EMB B-Chemical 0
- O 0
induced O 0
optic B-Disease 0
neuropathy I-Disease 0
, O 0
there O 0
was O 0
a O 0
mean O 0
loss O 0
of O 0
72 O 0
% O 0
nerve O 0
fiber O 0
layer O 0
thickness O 0
in O 0
the O 0
temporal O 0
quadrant O 0
( O 0
patient O 0
A O 0
, O 0
with O 0
eventual O 0
recovery O 0
of O 0
visual O 0
acuity O 0
and O 0
fields O 0
, O 0
58 O 0
% O 0
loss O 0
; O 0
patient O 0
B O 0
, O 0
with O 0
intermediate O 0
visual B-Disease 0
deficits I-Disease 0
, O 0
68 O 0
% O 0
loss O 0
; O 0
patient O 0
C O 0
, O 0
with O 0
chronic O 0
visual B-Disease 0
deficits I-Disease 0
, O 0
90 O 0
% O 0
loss O 0
) O 0
, O 0
with O 0
an O 0
average O 0
mean O 0
optic O 0
nerve O 0
thickness O 0
of O 0
26 O 0
+ O 0
/ O 0
- O 0
16 O 0
microm O 0
. O 0

There O 0
was O 0
a O 0
combined O 0
mean O 0
loss O 0
of O 0
46 O 0
% O 0
of O 0
fibers O 0
from O 0
the O 0
superior O 0
, O 0
inferior O 0
, O 0
and O 0
nasal O 0
quadrants O 0
in O 0
the O 0
( O 0
six O 0
) O 0
eyes O 0
of O 0
all O 0
three O 0
subjects O 0
( O 0
mean O 0
average O 0
thickness O 0
of O 0
55 O 0
+ O 0
/ O 0
- O 0
29 O 0
microm O 0
) O 0
. O 0

In O 0
both O 0
sets O 0
( O 0
four O 0
) O 0
of O 0
eyes O 0
of O 0
the O 0
subjects O 0
with O 0
persistent O 0
visual B-Disease 0
deficits I-Disease 0
( O 0
patients O 0
B O 0
and O 0
C O 0
) O 0
, O 0
there O 0
was O 0
an O 0
average O 0
loss O 0
of O 0
79 O 0
% O 0
of O 0
nerve O 0
fiber O 0
thickness O 0
in O 0
the O 0
temporal O 0
quadrant O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
OCT O 0
results O 0
in O 0
these O 0
patients O 0
with O 0
EMB B-Chemical 0
- O 0
induced O 0
optic B-Disease 0
neuropathy I-Disease 0
show O 0
considerable O 0
loss O 0
especially O 0
of O 0
the O 0
temporal O 0
fibers O 0
. O 0

This O 0
is O 0
consistent O 0
with O 0
prior O 0
histopathological O 0
studies O 0
that O 0
show O 0
predominant O 0
loss O 0
of O 0
parvo O 0
- O 0
cellular O 0
axons O 0
( O 0
or O 0
small O 0
- O 0
caliber O 0
axons O 0
) O 0
within O 0
the O 0
papillo O 0
- O 0
macular O 0
bundle O 0
in O 0
toxic O 0
or O 0
hereditary O 0
optic B-Disease 0
neuropathies I-Disease 0
. O 0

OCT O 0
can O 0
be O 0
a O 0
valuable O 0
tool O 0
in O 0
the O 0
quantitative O 0
analysis O 0
of O 0
optic B-Disease 0
neuropathies I-Disease 0
. O 0

Additionally O 0
, O 0
in O 0
terms O 0
of O 0
management O 0
of O 0
EMB B-Chemical 0
- O 0
induced O 0
optic B-Disease 0
neuropathy I-Disease 0
, O 0
it O 0
is O 0
important O 0
to O 0
properly O 0
manage O 0
ethambutol B-Chemical 0
dosing O 0
in O 0
patients O 0
with O 0
renal B-Disease 0
impairment I-Disease 0
and O 0
to O 0
achieve O 0
proper O 0
transition O 0
to O 0
a O 0
maintenance O 0
dose O 0
once O 0
an O 0
appropriate O 0
loading O 0
dose O 0
has O 0
been O 0
reached O 0
. O 0

Hypoxia B-Disease 0
in O 0
renal B-Disease 0
disease I-Disease 0
with O 0
proteinuria B-Disease 0
and O 0
/ O 0
or O 0
glomerular O 0
hypertension B-Disease 0
. O 0

Despite O 0
the O 0
increasing O 0
need O 0
to O 0
identify O 0
and O 0
quantify O 0
tissue O 0
oxygenation O 0
at O 0
the O 0
cellular O 0
level O 0
, O 0
relatively O 0
few O 0
methods O 0
have O 0
been O 0
available O 0
. O 0

In O 0
this O 0
study O 0
, O 0
we O 0
developed O 0
a O 0
new O 0
hypoxia B-Disease 0
- O 0
responsive O 0
reporter O 0
vector O 0
using O 0
a O 0
hypoxia B-Disease 0
- O 0
responsive O 0
element O 0
of O 0
the O 0
5 O 0
' O 0
vascular O 0
endothelial O 0
growth O 0
factor O 0
untranslated O 0
region O 0
and O 0
generated O 0
a O 0
novel O 0
hypoxia B-Disease 0
- O 0
sensing O 0
transgenic O 0
rat O 0
. O 0

We O 0
then O 0
applied O 0
this O 0
animal O 0
model O 0
to O 0
the O 0
detection O 0
of O 0
tubulointerstitial O 0
hypoxia B-Disease 0
in O 0
the O 0
diseased B-Disease 0
kidney I-Disease 0
. O 0

With O 0
this O 0
model O 0
, O 0
we O 0
were O 0
able O 0
to O 0
identify O 0
diffuse O 0
cortical O 0
hypoxia B-Disease 0
in O 0
the O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
- O 0
induced O 0
nephrotic B-Disease 0
syndrome I-Disease 0
and O 0
focal O 0
and O 0
segmental O 0
hypoxia B-Disease 0
in O 0
the O 0
remnant O 0
kidney O 0
model O 0
. O 0

Expression O 0
of O 0
the O 0
hypoxia B-Disease 0
- O 0
responsive O 0
transgene O 0
increased O 0
throughout O 0
the O 0
observation O 0
period O 0
, O 0
reaching O 0
2 O 0
. O 0
2 O 0
- O 0
fold O 0
at O 0
2 O 0
weeks O 0
in O 0
the O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
model O 0
and O 0
2 O 0
. O 0
6 O 0
- O 0
fold O 0
at O 0
4 O 0
weeks O 0
in O 0
the O 0
remnant O 0
kidney O 0
model O 0
, O 0
whereas O 0
that O 0
of O 0
vascular O 0
endothelial O 0
growth O 0
factor O 0
showed O 0
a O 0
mild O 0
decrease O 0
, O 0
reflecting O 0
distinct O 0
behaviors O 0
of O 0
the O 0
two O 0
genes O 0
. O 0

The O 0
degree O 0
of O 0
hypoxia B-Disease 0
showed O 0
a O 0
positive O 0
correlation O 0
with O 0
microscopic O 0
tubulointerstitial B-Disease 0
injury I-Disease 0
in O 0
both O 0
models O 0
. O 0

Finally O 0
, O 0
we O 0
identified O 0
the O 0
localization O 0
of O 0
proliferating O 0
cell O 0
nuclear O 0
antigen O 0
- O 0
positive O 0
, O 0
ED O 0
- O 0
1 O 0
- O 0
positive O 0
, O 0
and O 0
terminal O 0
dUTP O 0
nick O 0
- O 0
end O 0
labeled O 0
- O 0
positive O 0
cells O 0
in O 0
the O 0
hypoxic B-Disease 0
cortical O 0
area O 0
in O 0
the O 0
remnant O 0
kidney O 0
model O 0
. O 0

We O 0
propose O 0
here O 0
a O 0
possible O 0
pathological O 0
tie O 0
between O 0
chronic O 0
tubulointerstitial O 0
hypoxia B-Disease 0
and O 0
progressive O 0
glomerular B-Disease 0
diseases I-Disease 0
. O 0

Adequate O 0
timing O 0
of O 0
ribavirin B-Chemical 0
reduction O 0
in O 0
patients O 0
with O 0
hemolysis B-Disease 0
during O 0
combination O 0
therapy O 0
of O 0
interferon B-Chemical 0
and O 0
ribavirin B-Chemical 0
for O 0
chronic B-Disease 0
hepatitis I-Disease 0
C I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Hemolytic B-Disease 0
anemia I-Disease 0
is O 0
one O 0
of O 0
the O 0
major O 0
adverse O 0
events O 0
of O 0
the O 0
combination O 0
therapy O 0
of O 0
interferon B-Chemical 0
and O 0
ribavirin B-Chemical 0
. O 0

Because O 0
of O 0
ribavirin B-Chemical 0
- O 0
related O 0
hemolytic B-Disease 0
anemia I-Disease 0
, O 0
dose O 0
reduction O 0
is O 0
a O 0
common O 0
event O 0
in O 0
this O 0
therapy O 0
. O 0

In O 0
this O 0
clinical O 0
retrospective O 0
cohort O 0
study O 0
we O 0
have O 0
examined O 0
the O 0
suitable O 0
timing O 0
of O 0
ribavirin B-Chemical 0
reduction O 0
in O 0
patients O 0
with O 0
hemolysis B-Disease 0
during O 0
combination O 0
therapy O 0
. O 0

METHODS O 0
: O 0
Thirty O 0
- O 0
seven O 0
of O 0
160 O 0
patients O 0
who O 0
had O 0
HCV O 0
- O 0
genotype O 0
1b O 0
, O 0
had O 0
high O 0
virus O 0
load O 0
, O 0
and O 0
received O 0
24 O 0
- O 0
week O 0
combination O 0
therapy O 0
developed O 0
anemia B-Disease 0
with O 0
hemoglobin O 0
level O 0
< O 0
10 O 0
g O 0
/ O 0
dl O 0
or O 0
anemia B-Disease 0
- O 0
related O 0
signs O 0
during O 0
therapy O 0
. O 0

After O 0
that O 0
, O 0
these O 0
37 O 0
patients O 0
were O 0
reduced O 0
one O 0
tablet O 0
of O 0
ribavirin B-Chemical 0
( O 0
200 O 0
mg O 0
) O 0
per O 0
day O 0
. O 0

After O 0
reduction O 0
of O 0
ribavirin B-Chemical 0
, O 0
27 O 0
of O 0
37 O 0
patients O 0
could O 0
continue O 0
combination O 0
therapy O 0
for O 0
a O 0
total O 0
of O 0
24 O 0
weeks O 0
( O 0
group O 0
A O 0
) O 0
. O 0

However O 0
, O 0
10 O 0
of O 0
37 O 0
patients O 0
with O 0
reduction O 0
of O 0
ribavirin B-Chemical 0
could O 0
not O 0
continue O 0
combination O 0
therapy O 0
because O 0
their O 0
< O 0
8 O 0
. O 0
5 O 0
g O 0
/ O 0
dl O 0
hemoglobin O 0
values O 0
decreased O 0
to O 0
or O 0
anemia B-Disease 0
- O 0
related O 0
severe O 0
side O 0
effects O 0
occurred O 0
( O 0
group O 0
B O 0
) O 0
. O 0

We O 0
assessed O 0
the O 0
final O 0
efficacy O 0
and O 0
safety O 0
after O 0
reduction O 0
of O 0
ribavirin B-Chemical 0
in O 0
groups O 0
A O 0
and O 0
B O 0
. O 0

RESULTS O 0
: O 0
A O 0
sustained O 0
virological O 0
response O 0
( O 0
SVR O 0
) O 0
was O 0
29 O 0
. O 0
6 O 0
% O 0
( O 0
8 O 0
/ O 0
27 O 0
) O 0
in O 0
group O 0
A O 0
and O 0
10 O 0
% O 0
( O 0
1 O 0
/ O 0
10 O 0
) O 0
in O 0
group O 0
B O 0
, O 0
respectively O 0
. O 0

A O 0
34 O 0
. O 0
4 O 0
% O 0
( O 0
12 O 0
/ O 0
27 O 0
) O 0
of O 0
SVR O 0
+ O 0
biological O 0
response O 0
in O 0
group O 0
A O 0
was O 0
higher O 0
than O 0
10 O 0
% O 0
( O 0
1 O 0
/ O 0
10 O 0
) O 0
in O 0
group O 0
B O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
051 O 0
) O 0
, O 0
with O 0
slight O 0
significance O 0
. O 0

With O 0
respect O 0
to O 0
hemoglobin O 0
level O 0
at O 0
the O 0
time O 0
of O 0
ribavirin B-Chemical 0
reduction O 0
, O 0
a O 0
rate O 0
of O 0
continuation O 0
of O 0
therapy O 0
in O 0
patients O 0
with O 0
> O 0
or O 0
= O 0
10 O 0
g O 0
/ O 0
dl O 0
hemoglobin O 0
was O 0
higher O 0
than O 0
that O 0
in O 0
patients O 0
with O 0
< O 0
10 O 0
g O 0
/ O 0
dl O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
036 O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Reduction O 0
of O 0
ribavirin B-Chemical 0
at O 0
hemoglobin O 0
level O 0
> O 0
or O 0
= O 0
10 O 0
g O 0
/ O 0
dl O 0
is O 0
suitable O 0
in O 0
terms O 0
of O 0
efficacy O 0
and O 0
side O 0
effects O 0
. O 0

Aging O 0
process O 0
of O 0
epithelial O 0
cells O 0
of O 0
the O 0
rat O 0
prostate O 0
lateral O 0
lobe O 0
in O 0
experimental O 0
hyperprolactinemia B-Disease 0
induced O 0
by O 0
haloperidol B-Chemical 0
. O 0

The O 0
aim O 0
of O 0
the O 0
study O 0
was O 0
to O 0
examine O 0
the O 0
influence O 0
of O 0
hyperprolactinemia B-Disease 0
, O 0
induced O 0
by O 0
haloperidol B-Chemical 0
( O 0
HAL B-Chemical 0
) O 0
on O 0
age O 0
related O 0
morphology O 0
and O 0
function O 0
changes O 0
of O 0
epithelial O 0
cells O 0
in O 0
rat O 0
prostate O 0
lateral O 0
lobe O 0
. O 0

The O 0
study O 0
was O 0
performed O 0
on O 0
sexually O 0
mature O 0
male O 0
rats O 0
. O 0

Serum O 0
concentrations O 0
of O 0
prolactin O 0
( O 0
PRL B-Chemical 0
) O 0
and O 0
testosterone B-Chemical 0
( O 0
T B-Chemical 0
) O 0
were O 0
measured O 0
. O 0

Tissue O 0
sections O 0
were O 0
evaluated O 0
with O 0
light O 0
and O 0
electron O 0
microscopy O 0
. O 0

Immunohistochemical O 0
reactions O 0
for O 0
Anti O 0
- O 0
Proliferating O 0
Cell O 0
Nuclear O 0
Antigen O 0
( O 0
PCNA O 0
) O 0
were O 0
performed O 0
. O 0

In O 0
rats O 0
of O 0
the O 0
experimental O 0
group O 0
, O 0
the O 0
mean O 0
concentration O 0
of O 0
: O 0
PRL B-Chemical 0
was O 0
more O 0
than O 0
twice O 0
higher O 0
, O 0
whereas O 0
T B-Chemical 0
concentration O 0
was O 0
almost O 0
twice O 0
lower O 0
than O 0
that O 0
in O 0
the O 0
control O 0
group O 0
. O 0

Light O 0
microscopy O 0
visualized O 0
the O 0
following O 0
: O 0
hypertrophy B-Disease 0
and O 0
epithelium O 0
hyperplasia B-Disease 0
of O 0
the O 0
glandular O 0
ducts O 0
, O 0
associated O 0
with O 0
increased O 0
PCNA O 0
expression O 0
. O 0

Electron O 0
microscopy O 0
revealed O 0
changes O 0
in O 0
columnar O 0
epithelial O 0
cells O 0
, O 0
concerning O 0
organelles O 0
, O 0
engaged O 0
in O 0
protein O 0
synthesis O 0
and O 0
secretion O 0
. O 0

Relation O 0
of O 0
perfusion O 0
defects O 0
observed O 0
with O 0
myocardial O 0
contrast O 0
echocardiography O 0
to O 0
the O 0
severity O 0
of O 0
coronary B-Disease 0
stenosis I-Disease 0
: O 0
correlation O 0
with O 0
thallium B-Chemical 0
- O 0
201 O 0
single O 0
- O 0
photon O 0
emission O 0
tomography O 0
. O 0

It O 0
has O 0
been O 0
previously O 0
shown O 0
that O 0
myocardial O 0
contrast O 0
echocardiography O 0
is O 0
a O 0
valuable O 0
technique O 0
for O 0
delineating O 0
regions O 0
of O 0
myocardial O 0
underperfusion O 0
secondary O 0
to O 0
coronary B-Disease 0
occlusion I-Disease 0
and O 0
to O 0
critical O 0
coronary B-Disease 0
stenoses I-Disease 0
in O 0
the O 0
presence O 0
of O 0
hyperemic B-Disease 0
stimulation 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
myocardial O 0
contrast O 0
echocardiography O 0
performed O 0
with O 0
a O 0
stable O 0
solution O 0
of O 0
sonicated O 0
albumin O 0
could O 0
detect O 0
regions O 0
of O 0
myocardial O 0
underperfusion O 0
resulting O 0
from O 0
various O 0
degrees O 0
of O 0
coronary B-Disease 0
stenosis I-Disease 0
. O 0

The O 0
perfusion O 0
defect O 0
produced O 0
in O 0
16 O 0
open O 0
chest O 0
dogs O 0
was O 0
compared O 0
with O 0
the O 0
anatomic O 0
area O 0
at O 0
risk O 0
measured O 0
by O 0
the O 0
postmortem O 0
dual O 0
- O 0
perfusion O 0
technique O 0
and O 0
with O 0
thallium B-Chemical 0
- O 0
201 O 0
single O 0
- O 0
photon O 0
emission O 0
tomography O 0
( O 0
SPECT O 0
) O 0
. O 0

During O 0
a O 0
transient O 0
( O 0
20 O 0
- O 0
s O 0
) O 0
coronary B-Disease 0
occlusion I-Disease 0
, O 0
a O 0
perfusion O 0
defect O 0
was O 0
observed O 0
with O 0
contrast O 0
echocardiography O 0
in O 0
14 O 0
of O 0
the O 0
15 O 0
dogs O 0
in O 0
which O 0
the O 0
occlusion O 0
was O 0
produced O 0
. O 0

The O 0
perfusion O 0
defect O 0
correlated O 0
significantly O 0
with O 0
the O 0
anatomic O 0
area O 0
at O 0
risk O 0
( O 0
r O 0
= O 0
0 O 0
. O 0
74 O 0
; O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
002 O 0
) O 0
. O 0

During O 0
dipyridamole B-Chemical 0
- O 0
induced O 0
hyperemia B-Disease 0
, O 0
12 O 0
of O 0
the O 0
16 O 0
dogs O 0
with O 0
a O 0
partial O 0
coronary B-Disease 0
stenosis I-Disease 0
had O 0
a O 0
visible O 0
area O 0
of O 0
hypoperfusion O 0
by O 0
contrast O 0
echocardiography O 0
. O 0

The O 0
four O 0
dogs O 0
without O 0
a O 0
perfusion O 0
defect O 0
had O 0
a O 0
stenosis O 0
that O 0
resulted O 0
in O 0
a O 0
mild O 0
( O 0
0 O 0
% O 0
to O 0
50 O 0
% O 0
) O 0
reduction O 0
in O 0
dipyridamole B-Chemical 0
- O 0
induced O 0
hyperemia B-Disease 0
. O 0

The O 0
size O 0
of O 0
the O 0
perfusion O 0
defect O 0
during O 0
stenosis O 0
correlated O 0
significantly O 0
with O 0
the O 0
anatomic O 0
area O 0
at O 0
risk O 0
( O 0
r O 0
= O 0
0 O 0
. O 0
61 O 0
; O 0
p O 0
= O 0
0 O 0
. O 0
02 O 0
) O 0
. O 0

Thallium B-Chemical 0
- O 0
201 O 0
SPECT O 0
demonstrated O 0
a O 0
perfusion O 0
defect O 0
in O 0
all O 0
14 O 0
dogs O 0
analyzed O 0
during O 0
dipyridamole B-Chemical 0
- O 0
induced O 0
hyperemia B-Disease 0
; O 0
the O 0
size O 0
of O 0
the O 0
perfusion O 0
defect O 0
correlated O 0
with O 0
the O 0
anatomic O 0
area O 0
at O 0
risk 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
03 O 0
) O 0
and O 0
with O 0
the O 0
perfusion O 0
defect O 0
by O 0
contrast O 0
echocardiography 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
03 O 0
) O 0
. O 0

Thus O 0
, O 0
myocardial O 0
contrast O 0
echocardiography O 0
can O 0
be O 0
used O 0
to O 0
visualize O 0
and O 0
quantitate O 0
the O 0
amount O 0
of O 0
jeopardized O 0
myocardium O 0
during O 0
moderate O 0
to O 0
severe O 0
degrees O 0
of O 0
coronary B-Disease 0
stenosis I-Disease 0
. O 0

The O 0
results O 0
obtained O 0
show O 0
a O 0
correlation O 0
with O 0
the O 0
anatomic O 0
area O 0
at O 0
risk O 0
similar O 0
to O 0
that O 0
obtained O 0
with O 0
thallium B-Chemical 0
- O 0
201 O 0
SPECT O 0
. O 0

The O 0
activation O 0
of O 0
spinal 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
receptors O 0
may O 0
contribute O 0
to O 0
degeneration O 0
of O 0
spinal O 0
motor O 0
neurons O 0
induced O 0
by O 0
neuraxial O 0
morphine B-Chemical 0
after O 0
a O 0
noninjurious O 0
interval O 0
of O 0
spinal B-Disease 0
cord I-Disease 0
ischemia I-Disease 0
. O 0

We O 0
investigated O 0
the O 0
relationship O 0
between O 0
the O 0
degeneration O 0
of O 0
spinal O 0
motor O 0
neurons O 0
and O 0
activation O 0
of 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
receptors O 0
after O 0
neuraxial O 0
morphine B-Chemical 0
following O 0
a O 0
noninjurious O 0
interval O 0
of O 0
aortic B-Disease 0
occlusion I-Disease 0
in O 0
rats O 0
. O 0

Spinal B-Disease 0
cord I-Disease 0
ischemia I-Disease 0
was O 0
induced O 0
by O 0
aortic B-Disease 0
occlusion I-Disease 0
for O 0
6 O 0
min O 0
with O 0
a O 0
balloon O 0
catheter O 0
. O 0

In O 0
a O 0
microdialysis O 0
study O 0
, O 0
10 O 0
muL O 0
of O 0
saline O 0
( O 0
group O 0
C O 0
; O 0
n O 0
= O 0
8 O 0
) O 0
or O 0
30 O 0
mug O 0
of O 0
morphine B-Chemical 0
( O 0
group O 0
M O 0
; O 0
n O 0
= O 0
8 O 0
) O 0
was O 0
injected O 0
intrathecally O 0
( O 0
IT O 0
) O 0
0 O 0
. O 0
5 O 0
h O 0
after O 0
reflow O 0
, O 0
and O 0
30 O 0
mug O 0
of O 0
morphine B-Chemical 0
( O 0
group O 0
SM O 0
; O 0
n O 0
= O 0
8 O 0
) O 0
or O 0
10 O 0
muL O 0
of O 0
saline O 0
( O 0
group O 0
SC O 0
; O 0
n O 0
= O 0
8 O 0
) O 0
was O 0
injected O 0
IT O 0
0 O 0
. O 0
5 O 0
h O 0
after O 0
sham O 0
operation O 0
. O 0

Microdialysis O 0
samples O 0
were O 0
collected O 0
preischemia O 0
, O 0
before O 0
IT O 0
injection O 0
, O 0
and O 0
at O 0
2 O 0
, O 0
4 O 0
, O 0
8 O 0
, O 0
24 O 0
, O 0
and O 0
48 O 0
h O 0
of O 0
reperfusion O 0
( O 0
after O 0
IT O 0
injection O 0
) O 0
. O 0

Second O 0
, O 0
we O 0
investigated O 0
the O 0
effect O 0
of O 0
IT O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
( O 0
30 O 0
mug O 0
) O 0
on O 0
the O 0
histopathologic O 0
changes O 0
in O 0
the O 0
spinal O 0
cord O 0
after O 0
morphine B-Chemical 0
- O 0
induced O 0
spastic B-Disease 0
paraparesis I-Disease 0
. O 0

After O 0
IT O 0
morphine B-Chemical 0
, O 0
the O 0
cerebrospinal O 0
fluid O 0
( O 0
CSF O 0
) O 0
glutamate B-Chemical 0
concentration O 0
was O 0
increased O 0
in O 0
group O 0
M O 0
relative O 0
to O 0
both O 0
baseline O 0
and O 0
group O 0
C O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

This O 0
increase O 0
persisted O 0
for O 0
8 O 0
hrs O 0
. O 0

IT O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
significantly O 0
reduced O 0
the O 0
number O 0
of O 0
dark O 0
- O 0
stained O 0
alpha O 0
- O 0
motoneurons O 0
after O 0
morphine B-Chemical 0
- O 0
induced O 0
spastic B-Disease 0
paraparesis I-Disease 0
compared O 0
with O 0
the O 0
saline O 0
group O 0
. O 0

These O 0
data O 0
indicate O 0
that O 0
IT O 0
morphine B-Chemical 0
induces O 0
spastic B-Disease 0
paraparesis I-Disease 0
with O 0
a O 0
concomitant O 0
increase O 0
in O 0
CSF O 0
glutamate B-Chemical 0
, O 0
which O 0
is O 0
involved O 0
in O 0
NMDA B-Chemical 0
receptor O 0
activation O 0
. O 0

We O 0
suggest O 0
that O 0
opioids O 0
may O 0
be O 0
neurotoxic B-Disease 0
in O 0
the O 0
setting O 0
of O 0
spinal B-Disease 0
cord I-Disease 0
ischemia I-Disease 0
via O 0
NMDA B-Chemical 0
receptor O 0
activation O 0
. O 0

Acute O 0
low B-Disease 0
back I-Disease 0
pain I-Disease 0
during O 0
intravenous O 0
administration O 0
of O 0
amiodarone B-Chemical 0
: O 0
a O 0
report O 0
of O 0
two O 0
cases O 0
. O 0

Amiodarone B-Chemical 0
represents O 0
an O 0
effective O 0
antiarrhythmic O 0
drug O 0
for O 0
cardioversion O 0
of O 0
recent O 0
- O 0
onset O 0
atrial B-Disease 0
fibrillation I-Disease 0
( O 0
AF B-Disease 0
) O 0
and O 0
maintenance O 0
of O 0
sinus O 0
rhythm O 0
. O 0

We O 0
briefly O 0
describe O 0
two O 0
patients O 0
suffering O 0
from O 0
recent O 0
- O 0
onset O 0
atrial B-Disease 0
fibrillation I-Disease 0
, O 0
who O 0
experienced O 0
an O 0
acute O 0
devastating O 0
low B-Disease 0
back I-Disease 0
pain I-Disease 0
a O 0
few O 0
minutes O 0
after O 0
initiation O 0
of O 0
intravenous O 0
amiodarone B-Chemical 0
loading O 0
. O 0

Notably O 0
, O 0
this O 0
side O 0
effect O 0
has O 0
not O 0
been O 0
ever O 0
reported O 0
in O 0
the O 0
medical O 0
literature O 0
. O 0

Clinicians O 0
should O 0
be O 0
aware O 0
of O 0
this O 0
reaction O 0
since O 0
prompt O 0
termination O 0
of O 0
parenteral O 0
administration O 0
leads O 0
to O 0
complete O 0
resolution O 0
. O 0

Quantitative O 0
drug O 0
levels O 0
in O 0
stimulant O 0
psychosis B-Disease 0
: O 0
relationship O 0
to O 0
symptom O 0
severity O 0
, O 0
catecholamines B-Chemical 0
and O 0
hyperkinesia B-Disease 0
. O 0

To O 0
examine O 0
the O 0
relationship O 0
between O 0
quantitative O 0
stimulant O 0
drug O 0
levels O 0
, O 0
catecholamines B-Chemical 0
, O 0
and O 0
psychotic B-Disease 0
symptoms I-Disease 0
, O 0
nineteen O 0
patients O 0
in O 0
a O 0
psychiatric B-Disease 0
emergency O 0
service O 0
with O 0
a O 0
diagnosis O 0
of O 0
amphetamine B-Chemical 0
- O 0
or O 0
cocaine B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
were O 0
interviewed O 0
, O 0
and O 0
plasma O 0
and O 0
urine O 0
were O 0
collected O 0
for O 0
quantitative O 0
assays O 0
of O 0
stimulant O 0
drug O 0
and O 0
catecholamine B-Chemical 0
metabolite O 0
levels O 0
. O 0

Methamphetamine B-Chemical 0
or O 0
amphetamine B-Chemical 0
levels O 0
were O 0
related O 0
to O 0
several O 0
psychopathology O 0
scores O 0
and O 0
the O 0
global O 0
hyperkinesia B-Disease 0
rating O 0
. O 0

HVA O 0
levels O 0
were O 0
related O 0
to O 0
global O 0
hyperkinesia B-Disease 0
but O 0
not O 0
to O 0
psychopathology O 0
ratings O 0
. O 0

Although O 0
many O 0
other O 0
factors O 0
such O 0
as O 0
sensitization O 0
may O 0
play O 0
a O 0
role O 0
, O 0
intensity O 0
of O 0
stimulant O 0
- O 0
induced O 0
psychotic B-Disease 0
symptoms I-Disease 0
and O 0
stereotypies B-Disease 0
appears O 0
to O 0
be O 0
at O 0
least O 0
in O 0
part O 0
dose O 0
- O 0
related O 0
. O 0

Pheochromocytoma B-Disease 0
unmasked O 0
by O 0
amisulpride B-Chemical 0
and O 0
tiapride B-Chemical 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
describe O 0
the O 0
unmasking O 0
of O 0
pheochromocytoma B-Disease 0
in O 0
a O 0
patient O 0
treated O 0
with O 0
amisulpride B-Chemical 0
and O 0
tiapride B-Chemical 0
. O 0

CASE O 0
SUMMARY O 0
: O 0
A O 0
42 O 0
- O 0
year O 0
- O 0
old O 0
white O 0
man O 0
developed O 0
acute O 0
hypertension B-Disease 0
with O 0
severe O 0
headache B-Disease 0
and O 0
vomiting B-Disease 0
2 O 0
hours O 0
after O 0
the O 0
first O 0
doses O 0
of O 0
amisulpride B-Chemical 0
100 O 0
mg O 0
and O 0
tiapride B-Chemical 0
100 O 0
mg O 0
. O 0

Both O 0
drugs O 0
were O 0
immediately O 0
discontinued O 0
, O 0
and O 0
the O 0
patient O 0
recovered O 0
after O 0
subsequent O 0
nicardipine B-Chemical 0
and O 0
verapamil B-Chemical 0
treatment O 0
. O 0

Abdominal O 0
ultrasound O 0
showed O 0
an O 0
adrenal O 0
mass O 0
, O 0
and O 0
postoperative O 0
histologic O 0
examination O 0
confirmed O 0
the O 0
diagnosis O 0
of O 0
pheochromocytoma B-Disease 0
. O 0

DISCUSSION O 0
: O 0
Drug O 0
- O 0
induced O 0
symptoms O 0
of O 0
pheochromocytoma B-Disease 0
are O 0
often O 0
associated O 0
with O 0
the O 0
use O 0
of O 0
substituted O 0
benzamide B-Chemical 0
drugs O 0
, O 0
but O 0
the O 0
underlying O 0
mechanism O 0
is O 0
unknown O 0
. O 0

In O 0
our O 0
case O 0
, O 0
use O 0
of O 0
the O 0
Naranjo O 0
probability O 0
scale O 0
indicated O 0
a O 0
possible O 0
relationship O 0
between O 0
the O 0
hypertensive B-Disease 0
crisis O 0
and O 0
amisulpride B-Chemical 0
and O 0
tiapride B-Chemical 0
therapy O 0
. O 0

CONCLUSIONS O 0
: O 0
As O 0
of O 0
March O 0
24 O 0
, O 0
2005 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
amisulpride B-Chemical 0
- O 0
and O 0
tiapride B-Chemical 0
- O 0
induced O 0
hypertensive B-Disease 0
crisis O 0
in O 0
a O 0
patient O 0
with O 0
pheochromocytoma B-Disease 0
. O 0

Physicians O 0
and O 0
other O 0
healthcare O 0
professionals O 0
should O 0
be O 0
aware O 0
of O 0
this O 0
potential O 0
adverse O 0
effect O 0
of O 0
tiapride B-Chemical 0
and O 0
amisulpride B-Chemical 0
. O 0

Minor O 0
neurological B-Disease 0
dysfunction I-Disease 0
, O 0
cognitive O 0
development O 0
, O 0
and O 0
somatic O 0
development O 0
at O 0
the O 0
age O 0
of O 0
3 O 0
to O 0
7 O 0
years O 0
after O 0
dexamethasone B-Chemical 0
treatment O 0
in O 0
very O 0
- O 0
low O 0
birth O 0
- O 0
weight O 0
infants 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
assess O 0
minor O 0
neurological B-Disease 0
dysfunction I-Disease 0
, O 0
cognitive O 0
development O 0
, O 0
and O 0
somatic O 0
development O 0
after O 0
dexamethasone B-Chemical 0
therapy O 0
in O 0
very O 0
- O 0
low O 0
- O 0
birthweight O 0
infants O 0
. O 0

Thirty O 0
- O 0
three O 0
children O 0
after O 0
dexamethasone B-Chemical 0
treatment O 0
were O 0
matched O 0
to O 0
33 O 0
children O 0
without O 0
dexamethasone B-Chemical 0
treatment O 0
. O 0

Data O 0
were O 0
assessed O 0
at O 0
the O 0
age O 0
of O 0
3 O 0
- O 0
7 O 0
years O 0
. O 0

Dexamethasone B-Chemical 0
was O 0
started O 0
between O 0
the O 0
7th O 0
and O 0
the O 0
28th O 0
day O 0
of O 0
life O 0
over O 0
7 O 0
days O 0
with O 0
a O 0
total O 0
dose O 0
of O 0
2 O 0
. O 0
35 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
. O 0

Exclusion O 0
criteria O 0
were O 0
asphyxia B-Disease 0
, O 0
malformations B-Disease 0
, O 0
major O 0
surgical O 0
interventions O 0
, O 0
small O 0
for O 0
gestational O 0
age O 0
, O 0
intraventricular O 0
haemorrhage B-Disease 0
grades O 0
III O 0
and O 0
IV O 0
, O 0
periventricular B-Disease 0
leukomalacia I-Disease 0
, O 0
and O 0
severe O 0
psychomotor B-Disease 0
retardation I-Disease 0
. O 0

Each O 0
child O 0
was O 0
examined O 0
by O 0
a O 0
neuropediatrician O 0
for O 0
minor O 0
neurological B-Disease 0
dysfunctions I-Disease 0
and O 0
tested O 0
by O 0
a O 0
psychologist O 0
for O 0
cognitive O 0
development O 0
with O 0
a O 0
Kaufman O 0
Assessment O 0
Battery O 0
for O 0
Children O 0
and O 0
a O 0
Draw O 0
- O 0
a O 0
- O 0
Man O 0
Test O 0
. O 0

There O 0
were O 0
no O 0
differences O 0
in O 0
demographic O 0
data O 0
, O 0
growth O 0
, O 0
and O 0
socio O 0
- O 0
economic O 0
status O 0
between O 0
the O 0
two O 0
groups O 0
. O 0

Fine O 0
motor O 0
skills O 0
and O 0
gross O 0
motor O 0
function O 0
were O 0
significantly O 0
better O 0
in O 0
the O 0
control O 0
group O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

In O 0
the O 0
Draw O 0
- O 0
a O 0
- O 0
Man O 0
Test O 0
, O 0
the O 0
control O 0
group O 0
showed O 0
better O 0
results O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

There O 0
were O 0
no O 0
differences O 0
in O 0
development O 0
of O 0
speech O 0
, O 0
social O 0
development O 0
, O 0
and O 0
the O 0
Kaufman O 0
Assessment O 0
Battery O 0
for O 0
Children O 0
. O 0

After O 0
dexamethasone B-Chemical 0
treatment O 0
, O 0
children O 0
showed O 0
a O 0
higher O 0
rate O 0
of O 0
minor O 0
neurological B-Disease 0
dysfunctions I-Disease 0
. O 0

Neurological O 0
development O 0
was O 0
affected O 0
even O 0
without O 0
neurological O 0
diagnosis O 0
. O 0

Further O 0
long O 0
- O 0
term O 0
follow O 0
- O 0
up O 0
studies O 0
will O 0
be O 0
necessary O 0
to O 0
fully O 0
evaluate O 0
the O 0
impact O 0
of O 0
dexamethasone B-Chemical 0
on O 0
neurological O 0
and O 0
cognitive O 0
development O 0
. O 0

Valproic B-Chemical 0
acid I-Chemical 0
I O 0
: O 0
time O 0
course O 0
of O 0
lipid O 0
peroxidation O 0
biomarkers O 0
, O 0
liver B-Disease 0
toxicity I-Disease 0
, O 0
and O 0
valproic B-Chemical 0
acid I-Chemical 0
metabolite O 0
levels O 0
in O 0
rats O 0
. O 0

A O 0
single O 0
dose O 0
of O 0
valproic B-Chemical 0
acid I-Chemical 0
( O 0
VPA B-Chemical 0
) O 0
, O 0
which O 0
is O 0
a O 0
widely O 0
used O 0
antiepileptic O 0
drug O 0
, O 0
is O 0
associated O 0
with O 0
oxidative O 0
stress O 0
in O 0
rats O 0
, O 0
as O 0
recently O 0
demonstrated O 0
by O 0
elevated O 0
levels O 0
of O 0
15 B-Chemical 0
- I-Chemical 0
F I-Chemical 0
( I-Chemical 0
2t I-Chemical 0
) I-Chemical 0
- I-Chemical 0
isoprostane I-Chemical 0
( O 0
15 B-Chemical 0
- I-Chemical 0
F I-Chemical 0
( I-Chemical 0
2t I-Chemical 0
) I-Chemical 0
- I-Chemical 0
IsoP I-Chemical 0
) O 0
. O 0

To O 0
determine O 0
whether O 0
there O 0
was O 0
a O 0
temporal O 0
relationship O 0
between O 0
VPA B-Chemical 0
- O 0
associated O 0
oxidative O 0
stress O 0
and O 0
hepatotoxicity B-Disease 0
, O 0
adult O 0
male O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
were O 0
treated O 0
ip O 0
with O 0
VPA B-Chemical 0
( O 0
500 O 0
mg O 0
/ O 0
kg O 0
) O 0
or O 0
0 O 0
. O 0
9 O 0
% O 0
saline O 0
( O 0
vehicle O 0
) O 0
once O 0
daily O 0
for O 0
2 O 0
, O 0
4 O 0
, O 0
7 O 0
, O 0
10 O 0
, O 0
or O 0
14 O 0
days O 0
. O 0

Oxidative O 0
stress O 0
was O 0
assessed O 0
by O 0
determining O 0
plasma O 0
and O 0
liver O 0
levels O 0
of O 0
15 B-Chemical 0
- I-Chemical 0
F I-Chemical 0
( I-Chemical 0
2t I-Chemical 0
) I-Chemical 0
- I-Chemical 0
IsoP I-Chemical 0
, O 0
lipid B-Chemical 0
hydroperoxides I-Chemical 0
( O 0
LPO B-Chemical 0
) O 0
, O 0
and O 0
thiobarbituric B-Chemical 0
acid I-Chemical 0
reactive I-Chemical 0
substances I-Chemical 0
( O 0
TBARs B-Chemical 0
) O 0
. O 0

Plasma O 0
and O 0
liver O 0
15 B-Chemical 0
- I-Chemical 0
F I-Chemical 0
( I-Chemical 0
2t I-Chemical 0
) I-Chemical 0
- I-Chemical 0
IsoP I-Chemical 0
were O 0
elevated O 0
and O 0
reached O 0
a O 0
plateau O 0
after O 0
day O 0
2 O 0
of O 0
VPA B-Chemical 0
treatment O 0
compared O 0
to O 0
control O 0
. O 0

Liver O 0
LPO B-Chemical 0
levels O 0
were O 0
not O 0
elevated O 0
until O 0
day O 0
7 O 0
of O 0
treatment O 0
( O 0
1 O 0
. O 0
8 O 0
- O 0
fold O 0
versus O 0
control O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Liver O 0
and O 0
plasma O 0
TBARs B-Chemical 0
were O 0
not O 0
increased O 0
until O 0
14 O 0
days O 0
( O 0
2 O 0
- O 0
fold O 0
vs O 0
. O 0
control O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Liver B-Disease 0
toxicity I-Disease 0
was O 0
evaluated O 0
based O 0
on O 0
serum O 0
levels O 0
of O 0
alpha O 0
- O 0
glutathione B-Chemical 0
S O 0
- O 0
transferase O 0
( O 0
alpha O 0
- O 0
GST O 0
) O 0
and O 0
by O 0
histology O 0
. O 0

Serum O 0
alpha O 0
- O 0
GST O 0
levels O 0
were O 0
significantly O 0
elevated O 0
by O 0
day O 0
4 O 0
, O 0
which O 0
corresponded O 0
to O 0
hepatotoxicity B-Disease 0
as O 0
shown O 0
by O 0
the O 0
increasing O 0
incidence O 0
of O 0
inflammation B-Disease 0
of O 0
the O 0
liver O 0
capsule O 0
, O 0
necrosis B-Disease 0
, O 0
and O 0
steatosis B-Disease 0
throughout O 0
the O 0
study O 0
. O 0

The O 0
liver O 0
levels O 0
of O 0
beta O 0
- O 0
oxidation O 0
metabolites O 0
of O 0
VPA B-Chemical 0
were O 0
decreased O 0
by O 0
day O 0
14 O 0
, O 0
while O 0
the O 0
levels O 0
of O 0
4 B-Chemical 0
- I-Chemical 0
ene I-Chemical 0
- I-Chemical 0
VPA I-Chemical 0
and O 0
( O 0
E O 0
) O 0
- O 0
2 B-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
diene I-Chemical 0
- I-Chemical 0
VPA I-Chemical 0
were O 0
not O 0
elevated O 0
throughout O 0
the O 0
study O 0
. O 0

Overall O 0
, O 0
these O 0
findings O 0
indicate O 0
that O 0
VPA B-Chemical 0
treatment O 0
results O 0
in O 0
oxidative O 0
stress O 0
, O 0
as O 0
measured O 0
by O 0
levels O 0
of O 0
15 B-Chemical 0
- I-Chemical 0
F I-Chemical 0
( I-Chemical 0
2t I-Chemical 0
) I-Chemical 0
- I-Chemical 0
IsoP I-Chemical 0
, O 0
which O 0
precedes O 0
the O 0
onset O 0
of O 0
necrosis B-Disease 0
, O 0
steatosis B-Disease 0
, O 0
and O 0
elevated O 0
levels O 0
of O 0
serum O 0
alpha O 0
- O 0
GST O 0
. O 0

Assessment O 0
of O 0
perinatal O 0
hepatitis B-Disease 0
B I-Disease 0
and O 0
rubella B-Disease 0
prevention O 0
in O 0
New O 0
Hampshire O 0
delivery O 0
hospitals O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
evaluate O 0
current O 0
performance O 0
on O 0
recommended O 0
perinatal O 0
hepatitis B-Disease 0
B I-Disease 0
and O 0
rubella B-Disease 0
prevention O 0
practices O 0
in O 0
New O 0
Hampshire O 0
. O 0

METHODS O 0
: O 0
Data O 0
were O 0
extracted O 0
from O 0
2021 O 0
paired O 0
mother O 0
- O 0
infant O 0
records O 0
for O 0
the O 0
year O 0
2000 O 0
birth O 0
cohort O 0
in O 0
New O 0
Hampshire O 0
' O 0
s O 0
25 O 0
delivery O 0
hospitals O 0
. O 0

Assessment O 0
was O 0
done O 0
on O 0
the O 0
following O 0
: O 0
prenatal O 0
screening O 0
for O 0
hepatitis B-Disease 0
B I-Disease 0
and O 0
rubella B-Disease 0
, O 0
administration O 0
of O 0
the O 0
hepatitis B-Disease 0
B I-Disease 0
vaccine O 0
birth O 0
dose O 0
to O 0
all O 0
infants O 0
, O 0
administration O 0
of O 0
hepatitis B-Disease 0
B I-Disease 0
immune O 0
globulin O 0
to O 0
infants O 0
who O 0
were O 0
born O 0
to O 0
hepatitis B-Chemical 0
B I-Chemical 0
surface I-Chemical 0
antigen I-Chemical 0
- O 0
positive O 0
mothers O 0
, O 0
rubella B-Disease 0
immunity O 0
, O 0
and O 0
administration O 0
of O 0
in O 0
- O 0
hospital O 0
postpartum O 0
rubella B-Disease 0
vaccine O 0
to O 0
rubella B-Disease 0
nonimmune O 0
women O 0
. O 0

RESULTS O 0
: O 0
Prenatal O 0
screening O 0
rates O 0
for O 0
hepatitis B-Disease 0
B I-Disease 0
( O 0
98 O 0
. O 0
8 O 0
% O 0
) O 0
and O 0
rubella B-Disease 0
( O 0
99 O 0
. O 0
4 O 0
% O 0
) O 0
were O 0
high O 0
. O 0

Hepatitis B-Disease 0
B I-Disease 0
vaccine O 0
birth O 0
dose O 0
was O 0
administered O 0
to O 0
76 O 0
. O 0
2 O 0
% O 0
of O 0
all O 0
infants O 0
. O 0

All O 0
infants O 0
who O 0
were O 0
born O 0
to O 0
hepatitis B-Chemical 0
B I-Chemical 0
surface I-Chemical 0
antigen I-Chemical 0
- O 0
positive O 0
mothers O 0
also O 0
received O 0
hepatitis B-Disease 0
B I-Disease 0
immune O 0
globulin O 0
. O 0

Multivariate O 0
logistic O 0
regression O 0
showed O 0
that O 0
the O 0
month O 0
of O 0
delivery O 0
and O 0
infant O 0
birth O 0
weight O 0
were O 0
independent O 0
predictors O 0
of O 0
hepatitis B-Disease 0
B I-Disease 0
vaccination O 0
. O 0

The O 0
proportion O 0
of O 0
infants O 0
who O 0
were O 0
vaccinated O 0
in O 0
January O 0
and O 0
February O 0
2000 O 0
( O 0
48 O 0
. O 0
5 O 0
% O 0
and O 0
67 O 0
. O 0
5 O 0
% O 0
, O 0
respectively O 0
) O 0
was O 0
less O 0
than O 0
any O 0
other O 0
months O 0
, O 0
whereas O 0
the O 0
proportion O 0
who O 0
were O 0
vaccinated O 0
in O 0
December O 0
2000 O 0
( O 0
88 O 0
. O 0
2 O 0
% O 0
) O 0
was O 0
the O 0
highest O 0
. O 0

Women O 0
who O 0
were O 0
born O 0
between O 0
1971 O 0
and O 0
1975 O 0
had O 0
the O 0
highest O 0
rate O 0
of O 0
rubella B-Disease 0
nonimmunity O 0
( O 0
9 O 0
. O 0
5 O 0
% O 0
) O 0
. O 0

In O 0
- O 0
hospital O 0
postpartum O 0
rubella B-Disease 0
vaccine O 0
administration O 0
was O 0
documented O 0
for O 0
75 O 0
. O 0
6 O 0
% O 0
of O 0
nonimmune O 0
women O 0
. O 0

CONCLUSION O 0
: O 0
This O 0
study O 0
documents O 0
good O 0
compliance O 0
in O 0
New O 0
Hampshire O 0
' O 0
s O 0
birthing O 0
hospitals O 0
with O 0
national O 0
guidelines O 0
for O 0
perinatal O 0
hepatitis B-Disease 0
B I-Disease 0
and O 0
rubella B-Disease 0
prevention O 0
and O 0
highlights O 0
potential O 0
areas O 0
for O 0
improvement O 0
. O 0

Succinylcholine B-Chemical 0
- O 0
induced O 0
masseter B-Disease 0
muscle I-Disease 0
rigidity I-Disease 0
during O 0
bronchoscopic O 0
removal O 0
of O 0
a O 0
tracheal O 0
foreign O 0
body O 0
. O 0

Masseter B-Disease 0
muscle I-Disease 0
rigidity I-Disease 0
during O 0
general O 0
anesthesia O 0
is O 0
considered O 0
an O 0
early O 0
warning O 0
sign O 0
of O 0
a O 0
possible O 0
episode O 0
of O 0
malignant B-Disease 0
hyperthermia I-Disease 0
. O 0

The O 0
decision O 0
whether O 0
to O 0
continue O 0
or O 0
discontinue O 0
the O 0
procedure O 0
depends O 0
on O 0
the O 0
urgency O 0
of O 0
the O 0
surgery O 0
and O 0
severity O 0
of O 0
masseter B-Disease 0
muscle I-Disease 0
rigidity I-Disease 0
. O 0

Here O 0
, O 0
we O 0
describe O 0
a O 0
case O 0
of O 0
severe O 0
masseter B-Disease 0
muscle I-Disease 0
rigidity I-Disease 0
( O 0
jaw B-Disease 0
of I-Disease 0
steel I-Disease 0
) O 0
after O 0
succinylcholine B-Chemical 0
( O 0
Sch B-Chemical 0
) O 0
administration O 0
during O 0
general O 0
anesthetic O 0
management O 0
for O 0
rigid O 0
bronchoscopic O 0
removal O 0
of O 0
a O 0
tracheal O 0
foreign O 0
body O 0
. O 0

Anesthesia O 0
was O 0
continued O 0
uneventfully O 0
with O 0
propofol B-Chemical 0
infusion O 0
while O 0
all O 0
facilities O 0
were O 0
available O 0
to O 0
detect O 0
and O 0
treat O 0
malignant B-Disease 0
hyperthermia I-Disease 0
. O 0

Dexrazoxane B-Chemical 0
protects O 0
against O 0
myelosuppression B-Disease 0
from O 0
the O 0
DNA O 0
cleavage O 0
- O 0
enhancing O 0
drugs O 0
etoposide B-Chemical 0
and O 0
daunorubicin B-Chemical 0
but O 0
not O 0
doxorubicin B-Chemical 0
. O 0

PURPOSE O 0
: O 0
The O 0
anthracyclines B-Chemical 0
daunorubicin B-Chemical 0
and O 0
doxorubicin B-Chemical 0
and O 0
the O 0
epipodophyllotoxin B-Chemical 0
etoposide B-Chemical 0
are O 0
potent O 0
DNA O 0
cleavage O 0
- O 0
enhancing O 0
drugs O 0
that O 0
are O 0
widely O 0
used O 0
in O 0
clinical O 0
oncology O 0
; O 0
however O 0
, O 0
myelosuppression B-Disease 0
and O 0
cardiac B-Disease 0
toxicity I-Disease 0
limit O 0
their O 0
use O 0
. O 0

Dexrazoxane B-Chemical 0
( O 0
ICRF B-Chemical 0
- I-Chemical 0
187 I-Chemical 0
) O 0
is O 0
recommended O 0
for O 0
protection O 0
against O 0
anthracycline B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

EXPERIMENTAL O 0
DESIGN O 0
: O 0
Because O 0
of O 0
their O 0
widespread O 0
use O 0
, O 0
the O 0
hematologic B-Disease 0
toxicity I-Disease 0
following O 0
coadministration O 0
of O 0
dexrazoxane B-Chemical 0
and O 0
these O 0
three O 0
structurally O 0
different O 0
DNA O 0
cleavage O 0
enhancers O 0
was O 0
investigated O 0
: O 0
Sensitivity O 0
of O 0
human O 0
and O 0
murine O 0
blood O 0
progenitor O 0
cells O 0
to O 0
etoposide B-Chemical 0
, O 0
daunorubicin B-Chemical 0
, O 0
and O 0
doxorubicin B-Chemical 0
+ O 0
/ O 0
- O 0
dexrazoxane B-Chemical 0
was O 0
determined O 0
in O 0
granulocyte O 0
- O 0
macrophage O 0
colony O 0
forming O 0
assays O 0
. O 0

Likewise O 0
, O 0
in O 0
vivo O 0
, O 0
B6D2F1 O 0
mice O 0
were O 0
treated O 0
with O 0
etoposide B-Chemical 0
, O 0
daunorubicin B-Chemical 0
, O 0
and O 0
doxorubicin B-Chemical 0
, O 0
with O 0
or O 0
without O 0
dexrazoxane B-Chemical 0
over O 0
a O 0
wide O 0
range O 0
of O 0
doses O 0
: O 0
posttreatment O 0
, O 0
a O 0
full O 0
hematologic O 0
evaluation O 0
was O 0
done O 0
. O 0

RESULTS O 0
: O 0
Nontoxic O 0
doses O 0
of O 0
dexrazoxane B-Chemical 0
reduced O 0
myelosuppression B-Disease 0
and O 0
weight B-Disease 0
loss I-Disease 0
from O 0
daunorubicin B-Chemical 0
and O 0
etoposide B-Chemical 0
in O 0
mice O 0
and O 0
antagonized O 0
their O 0
antiproliferative O 0
effects O 0
in O 0
the O 0
colony O 0
assay O 0
; O 0
however O 0
, O 0
dexrazoxane B-Chemical 0
neither O 0
reduced O 0
myelosuppression B-Disease 0
, O 0
weight B-Disease 0
loss I-Disease 0
, O 0
nor O 0
the O 0
in O 0
vitro O 0
cytotoxicity B-Disease 0
from O 0
doxorubicin B-Chemical 0
. O 0

CONCLUSION O 0
: O 0
Although O 0
our O 0
findings O 0
support O 0
the O 0
observation O 0
that O 0
dexrazoxane B-Chemical 0
reduces O 0
neither O 0
hematologic O 0
activity O 0
nor O 0
antitumor O 0
activity O 0
from O 0
doxorubicin B-Chemical 0
clinically O 0
, O 0
the O 0
potent O 0
antagonism O 0
of O 0
daunorubicin B-Chemical 0
activity O 0
raises O 0
concern O 0
; O 0
a O 0
possible O 0
interference O 0
with O 0
anticancer O 0
efficacy O 0
certainly O 0
would O 0
call O 0
for O 0
renewed O 0
attention O 0
. O 0

Our O 0
data O 0
also O 0
suggest O 0
that O 0
significant O 0
etoposide B-Chemical 0
dose O 0
escalation O 0
is O 0
perhaps O 0
possible O 0
by O 0
the O 0
use O 0
of O 0
dexrazoxane B-Chemical 0
. O 0

Clinical O 0
trials O 0
in O 0
patients O 0
with O 0
brain O 0
metastases B-Disease 0
combining O 0
dexrazoxane B-Chemical 0
and O 0
high O 0
doses O 0
of O 0
etoposide B-Chemical 0
is O 0
ongoing O 0
with O 0
the O 0
aim O 0
of O 0
improving O 0
efficacy O 0
without O 0
aggravating O 0
hematologic B-Disease 0
toxicity I-Disease 0
. O 0

If O 0
successful O 0
, O 0
this O 0
represents O 0
an O 0
exciting O 0
mechanism O 0
for O 0
pharmacologic O 0
regulation O 0
of O 0
side O 0
effects O 0
from O 0
cytotoxic O 0
chemotherapy O 0
. O 0

Assessment O 0
of O 0
the O 0
onset O 0
and O 0
persistence O 0
of O 0
amnesia B-Disease 0
during O 0
procedural O 0
sedation O 0
with O 0
propofol B-Chemical 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
assess O 0
patients O 0
' O 0
ability O 0
to O 0
repeat O 0
and O 0
recall O 0
words O 0
presented O 0
to O 0
them O 0
while O 0
undergoing O 0
procedural O 0
sedation O 0
with O 0
propofol B-Chemical 0
, O 0
and O 0
correlate O 0
their O 0
recall O 0
with O 0
their O 0
level O 0
of O 0
awareness O 0
as O 0
measured O 0
by O 0
bispectral O 0
index O 0
( O 0
BIS O 0
) O 0
monitoring O 0
. O 0

METHODS O 0
: O 0
This O 0
was O 0
a O 0
prospective O 0
, O 0
single O 0
- O 0
intervention O 0
study O 0
of O 0
consenting O 0
adult O 0
patients O 0
undergoing O 0
procedural O 0
sedation O 0
with O 0
propofol B-Chemical 0
between O 0
December O 0
28 O 0
, O 0
2002 O 0
, O 0
and O 0
October O 0
31 O 0
, O 0
2003 O 0
. O 0

BIS O 0
monitoring O 0
was O 0
initiated O 0
starting O 0
3 O 0
minutes O 0
before O 0
the O 0
procedure O 0
and O 0
continuing O 0
until O 0
the O 0
patient O 0
had O 0
regained O 0
baseline O 0
mental O 0
status O 0
. O 0

At O 0
1 O 0
- O 0
minute O 0
intervals O 0
during O 0
the O 0
procedural O 0
sedation O 0
, O 0
until O 0
the O 0
patient O 0
regained O 0
baseline O 0
mental O 0
status O 0
at O 0
the O 0
end O 0
of O 0
the O 0
procedure O 0
, O 0
a O 0
word O 0
from O 0
a O 0
standardized O 0
list O 0
was O 0
read O 0
aloud O 0
, O 0
and O 0
the O 0
patient O 0
was O 0
asked O 0
to O 0
immediately O 0
repeat O 0
the O 0
word O 0
to O 0
the O 0
investigator O 0
. O 0

The O 0
BIS O 0
score O 0
at O 0
the O 0
time O 0
the O 0
word O 0
was O 0
read O 0
and O 0
the O 0
patient O 0
' O 0
s O 0
ability O 0
to O 0
repeat O 0
the O 0
word O 0
were O 0
recorded O 0
. O 0

After O 0
the O 0
procedure O 0
, O 0
the O 0
patient O 0
was O 0
asked O 0
to O 0
state O 0
all O 0
of O 0
the O 0
words O 0
from O 0
the O 0
list O 0
that O 0
he O 0
or O 0
she O 0
could O 0
recall O 0
, O 0
and O 0
to O 0
identify O 0
the O 0
last O 0
word O 0
recalled O 0
from O 0
prior O 0
to O 0
the O 0
start O 0
of O 0
the O 0
procedure O 0
and O 0
the O 0
first O 0
word O 0
recalled O 0
from O 0
after O 0
the O 0
procedure O 0
was O 0
completed O 0
. O 0

RESULTS O 0
: O 0
Seventy O 0
- O 0
five O 0
consenting O 0
patients O 0
were O 0
enrolled O 0
; O 0
one O 0
patient O 0
was O 0
excluded O 0
from O 0
data O 0
analysis O 0
for O 0
a O 0
protocol O 0
violation O 0
. O 0

No O 0
serious O 0
adverse O 0
events O 0
were O 0
noted O 0
during O 0
the O 0
procedural O 0
sedations O 0
. O 0

The O 0
mean O 0
( O 0
+ O 0
/ O 0
- O 0
standard O 0
deviation O 0
) O 0
time O 0
of O 0
data O 0
collection O 0
was O 0
16 O 0
. O 0
4 O 0
minutes O 0
( O 0
+ O 0
/ O 0
- O 0
7 O 0
. O 0
1 O 0
; O 0
range O 0
5 O 0
to O 0
34 O 0
minutes O 0
) O 0
. O 0

The O 0
mean O 0
initial O 0
( O 0
preprocedure O 0
) O 0
BIS O 0
score O 0
was O 0
97 O 0
. O 0
1 O 0
( O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
3 O 0
; O 0
range O 0
92 O 0
to O 0
99 O 0
) O 0
. O 0

The O 0
mean O 0
lowest O 0
BIS O 0
score O 0
occurring O 0
during O 0
these O 0
procedural O 0
sedations O 0
was O 0
66 O 0
. O 0
9 O 0
( O 0
+ O 0
/ O 0
- O 0
14 O 0
. O 0
4 O 0
; O 0
range O 0
33 O 0
to O 0
91 O 0
) O 0
. O 0

The O 0
mean O 0
lowest O 0
BIS O 0
score O 0
corresponding O 0
to O 0
the O 0
ability O 0
of O 0
the O 0
patient O 0
to O 0
immediately O 0
repeat O 0
words O 0
read O 0
from O 0
the O 0
list O 0
was O 0
77 O 0
. O 0
1 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
74 O 0
. O 0
3 O 0
to O 0
80 O 0
. O 0
0 O 0
) O 0
. O 0

The O 0
mean O 0
highest O 0
BIS O 0
score O 0
corresponding O 0
to O 0
the O 0
inability B-Disease 0
to I-Disease 0
repeat I-Disease 0
words I-Disease 0
was O 0
81 O 0
. O 0
5 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
78 O 0
. O 0
1 O 0
to O 0
84 O 0
. O 0
8 O 0
) O 0
. O 0

The O 0
mean O 0
BIS O 0
score O 0
corresponding O 0
to O 0
the O 0
last O 0
word O 0
recalled O 0
from O 0
prior O 0
to O 0
the O 0
initiation O 0
of O 0
the O 0
sedation O 0
was O 0
96 O 0
. O 0
7 O 0
( O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
4 O 0
; O 0
range O 0
84 O 0
to O 0
98 O 0
) O 0
. O 0

The O 0
mean O 0
BIS O 0
score O 0
corresponding O 0
to O 0
the O 0
first O 0
word O 0
recalled O 0
after O 0
the O 0
procedure O 0
was O 0
completed O 0
was O 0
91 O 0
. O 0
2 O 0
( O 0
95 O 0
% O 0
CI O 0
= O 0
88 O 0
. O 0
1 O 0
to O 0
94 O 0
. O 0
3 O 0
) O 0
. O 0

All O 0
patients O 0
recalled O 0
at O 0
least O 0
one O 0
word O 0
that O 0
had O 0
been O 0
read O 0
to O 0
them O 0
during O 0
the O 0
protocol O 0
. O 0

The O 0
mean O 0
lowest O 0
BIS O 0
score O 0
for O 0
any O 0
recalled O 0
word O 0
was O 0
91 O 0
. O 0
5 O 0
( O 0
+ O 0
/ O 0
- O 0
11 O 0
. O 0
1 O 0
; O 0
range O 0
79 O 0
to O 0
98 O 0
) O 0
, O 0
and O 0
no O 0
words O 0
were O 0
recalled O 0
when O 0
the O 0
corresponding O 0
BIS O 0
score O 0
was O 0
less O 0
than O 0
90 O 0
. O 0

CONCLUSIONS O 0
: O 0
There O 0
is O 0
a O 0
range O 0
of O 0
BIS O 0
scores O 0
during O 0
which O 0
sedated O 0
patients O 0
are O 0
able O 0
to O 0
repeat O 0
words O 0
read O 0
to O 0
them O 0
but O 0
are O 0
not O 0
able O 0
to O 0
subsequently O 0
recall O 0
these O 0
words O 0
. O 0

Furthermore O 0
, O 0
patients O 0
had O 0
no O 0
recall O 0
of O 0
words O 0
repeated O 0
prior O 0
to O 0
procedural O 0
sedation O 0
in O 0
BIS O 0
ranges O 0
associated O 0
with O 0
recall O 0
after O 0
procedural O 0
sedation O 0
, O 0
suggestive O 0
of O 0
retrograde B-Disease 0
amnesia I-Disease 0
. O 0

Amiodarone B-Chemical 0
pulmonary B-Disease 0
toxicity I-Disease 0
. O 0

Amiodarone B-Chemical 0
is O 0
an O 0
effective O 0
antiarrhythmic O 0
agent O 0
whose O 0
utility O 0
is O 0
limited O 0
by O 0
many O 0
side O 0
- O 0
effects O 0
, O 0
the O 0
most O 0
problematic O 0
being O 0
pneumonitis B-Disease 0
. O 0

The O 0
pulmonary B-Disease 0
toxicity I-Disease 0
of O 0
amiodarone B-Chemical 0
is O 0
thought O 0
to O 0
result O 0
from O 0
direct O 0
injury O 0
related O 0
to O 0
the O 0
intracellular O 0
accumulation O 0
of O 0
phospholipid O 0
and O 0
T O 0
cell O 0
- O 0
mediated O 0
hypersensitivity B-Disease 0
pneumonitis I-Disease 0
. O 0

The O 0
clinical O 0
and O 0
radiographic O 0
features O 0
of O 0
amiodarone B-Chemical 0
- O 0
induced O 0
pulmonary B-Disease 0
toxicity I-Disease 0
are O 0
characteristic O 0
but O 0
nonspecific O 0
. O 0

The O 0
diagnosis O 0
depends O 0
on O 0
exclusion O 0
of O 0
other O 0
entities O 0
, O 0
such O 0
as O 0
heart B-Disease 0
failure I-Disease 0
, O 0
infection B-Disease 0
, O 0
and O 0
malignancy B-Disease 0
. O 0

While O 0
withdrawal O 0
of O 0
amiodarone B-Chemical 0
leads O 0
to O 0
clinical O 0
improvement O 0
in O 0
majority O 0
of O 0
cases O 0
, O 0
this O 0
is O 0
not O 0
always O 0
possible O 0
or O 0
advisable O 0
. O 0

Dose O 0
reduction O 0
or O 0
concomitant O 0
steroid B-Chemical 0
therapy O 0
may O 0
have O 0
a O 0
role O 0
in O 0
selected O 0
patients O 0
. O 0

Two O 0
prodrugs O 0
of O 0
potent O 0
and O 0
selective O 0
GluR5 O 0
kainate B-Chemical 0
receptor O 0
antagonists O 0
actives O 0
in O 0
three O 0
animal O 0
models O 0
of O 0
pain B-Disease 0
. O 0

Amino O 0
acids O 0
5 O 0
and O 0
7 O 0
, O 0
two O 0
potent O 0
and O 0
selective O 0
competitive O 0
GluR5 O 0
KA B-Chemical 0
receptor O 0
antagonists O 0
, O 0
exhibited O 0
high O 0
GluR5 O 0
receptor O 0
affinity O 0
over O 0
other O 0
glutamate B-Chemical 0
receptors O 0
. O 0

Their O 0
ester O 0
prodrugs O 0
6 O 0
and O 0
8 O 0
were O 0
orally O 0
active O 0
in O 0
three O 0
models O 0
of O 0
pain B-Disease 0
: O 0
reversal O 0
of O 0
formalin B-Chemical 0
- O 0
induced O 0
paw O 0
licking O 0
, O 0
carrageenan B-Chemical 0
- O 0
induced O 0
thermal B-Disease 0
hyperalgesia I-Disease 0
, O 0
and O 0
capsaicin B-Chemical 0
- O 0
induced O 0
mechanical B-Disease 0
hyperalgesia I-Disease 0
. O 0

Possible O 0
azithromycin B-Chemical 0
- O 0
associated O 0
hiccups 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
persistent O 0
hiccups B-Disease 0
associated O 0
by O 0
azithromycin B-Chemical 0
therapy O 0
. O 0

CASE O 0
SUMMARY O 0
: O 0
A O 0
76 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
presented O 0
with O 0
persistent O 0
hiccups B-Disease 0
after O 0
beginning O 0
azithromycin B-Chemical 0
for O 0
the O 0
treatment O 0
of O 0
pharyngitis B-Disease 0
. O 0

Hiccups B-Disease 0
were O 0
persistent O 0
and O 0
exhausting O 0
. O 0

Discontinuation O 0
of O 0
azithromycin B-Chemical 0
and O 0
therapy O 0
with O 0
baclofen B-Chemical 0
finally O 0
resolved O 0
hiccups B-Disease 0
. O 0

No O 0
organic O 0
cause O 0
of O 0
hiccups B-Disease 0
was O 0
identified O 0
despite O 0
extensive O 0
investigation O 0
. O 0

DISCUSSION O 0
: O 0
Pharmacotherapeutic O 0
agents O 0
have O 0
been O 0
uncommonly O 0
associated O 0
with O 0
hiccups B-Disease 0
. O 0

Corticosteroids O 0
( O 0
dexamethasone B-Chemical 0
and O 0
methylprednisolone B-Chemical 0
) O 0
, O 0
benzodiazepines B-Chemical 0
( O 0
midazolam B-Chemical 0
) O 0
and O 0
general O 0
anaesthesia O 0
have O 0
been O 0
the O 0
specific O 0
agents O 0
mentioned O 0
most O 0
frequently O 0
in O 0
the O 0
literature O 0
as O 0
being O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
hiccups B-Disease 0
. O 0

Few O 0
cases O 0
of O 0
drug O 0
- O 0
induced O 0
hiccups B-Disease 0
have O 0
been O 0
reported O 0
related O 0
to O 0
macrolide B-Chemical 0
antimicrobials O 0
. O 0

Using O 0
the O 0
Naranjo O 0
adverse O 0
effect O 0
reaction O 0
probability O 0
scale O 0
this O 0
event O 0
could O 0
be O 0
classified O 0
as O 0
possible O 0
( O 0
score O 0
5 O 0
points O 0
) O 0
, O 0
mostly O 0
because O 0
of O 0
the O 0
close O 0
temporal O 0
sequence O 0
, O 0
previous O 0
reports O 0
on O 0
this O 0
reaction O 0
with O 0
other O 0
macrolides B-Chemical 0
and O 0
the O 0
absence O 0
of O 0
any O 0
alternative O 0
explanation O 0
for O 0
hiccups B-Disease 0
. O 0

Our O 0
hypothesis O 0
is O 0
that O 0
a O 0
vagal O 0
mechanism O 0
mediated O 0
by O 0
azithromycin B-Chemical 0
could O 0
be O 0
the O 0
pathogenesis O 0
of O 0
hiccups B-Disease 0
in O 0
our O 0
patient O 0
. O 0

CONCLUSIONS O 0
: O 0
Diagnosis O 0
of O 0
drug O 0
- O 0
induced O 0
hiccups B-Disease 0
is O 0
difficult O 0
and O 0
often O 0
achieved O 0
only O 0
by O 0
a O 0
process O 0
of O 0
elimination O 0
. O 0

However O 0
, O 0
macrolide B-Chemical 0
antimicrobials O 0
have O 0
been O 0
reported O 0
to O 0
be O 0
associated O 0
with O 0
hiccups B-Disease 0
and O 0
vagal O 0
mechanism O 0
could O 0
explain O 0
the O 0
development O 0
of O 0
this O 0
side O 0
- O 0
effect O 0
. O 0

Calcium B-Chemical 0
carbonate I-Chemical 0
toxicity B-Disease 0
: O 0
the O 0
updated O 0
milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
; O 0
report O 0
of O 0
3 O 0
cases O 0
and O 0
review O 0
of O 0
the O 0
literature O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
describe O 0
3 O 0
patients O 0
with O 0
calcium B-Chemical 0
carbonate I-Chemical 0
- O 0
induced O 0
hypercalcemia B-Disease 0
and O 0
gain O 0
insights O 0
into O 0
the O 0
cause O 0
and O 0
management O 0
of O 0
the O 0
milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
. O 0

METHODS O 0
: O 0
We O 0
report O 0
the O 0
clinical O 0
and O 0
laboratory O 0
data O 0
in O 0
3 O 0
patients O 0
who O 0
presented O 0
with O 0
severe O 0
hypercalcemia B-Disease 0
( O 0
corrected O 0
serum O 0
calcium B-Chemical 0
> O 0
or O 0
= O 0
14 O 0
mg O 0
/ O 0
dL O 0
) O 0
and O 0
review O 0
the O 0
pertinent O 0
literature O 0
on O 0
milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
. O 0

RESULTS O 0
: O 0
The O 0
3 O 0
patients O 0
had O 0
acute B-Disease 0
renal I-Disease 0
insufficiency I-Disease 0
, O 0
relative O 0
metabolic B-Disease 0
alkalosis I-Disease 0
, O 0
and O 0
low O 0
parathyroid O 0
hormone O 0
( O 0
PTH O 0
) O 0
, O 0
PTH O 0
- O 0
related O 0
peptide O 0
, O 0
and O 0
1 B-Chemical 0
, I-Chemical 0
25 I-Chemical 0
- I-Chemical 0
dihydroxyvitamin I-Chemical 0
D I-Chemical 0
concentrations O 0
. O 0

No O 0
malignant O 0
lesion O 0
was O 0
found O 0
. O 0

Treatment O 0
included O 0
aggressive O 0
hydration O 0
and O 0
varied O 0
amounts O 0
of O 0
furosemide B-Chemical 0
. O 0

The O 0
2 O 0
patients O 0
with O 0
the O 0
higher O 0
serum O 0
calcium B-Chemical 0
concentrations O 0
received O 0
pamidronate B-Chemical 0
intravenously O 0
( O 0
60 O 0
and O 0
30 O 0
mg O 0
, O 0
respectively O 0
) O 0
, O 0
which O 0
caused O 0
severe O 0
hypocalcemia B-Disease 0
. O 0

Of O 0
the O 0
3 O 0
patients O 0
, O 0
2 O 0
were O 0
ingesting O 0
acceptable O 0
doses O 0
of O 0
elemental O 0
calcium B-Chemical 0
( O 0
1 O 0
g O 0
and O 0
2 O 0
g O 0
daily O 0
, O 0
respectively O 0
) O 0
in O 0
the O 0
form O 0
of O 0
calcium B-Chemical 0
carbonate I-Chemical 0
. O 0

In O 0
addition O 0
to O 0
our O 0
highlighted O 0
cases O 0
, O 0
we O 0
review O 0
the O 0
history O 0
, O 0
classification O 0
, O 0
pathophysiologic O 0
features O 0
, O 0
and O 0
treatment O 0
of O 0
milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
and O 0
summarize O 0
the O 0
cases O 0
reported O 0
from O 0
early O 0
1995 O 0
to O 0
November O 0
2003 O 0
. O 0

CONCLUSION O 0
: O 0
Milk B-Disease 0
- I-Disease 0
alkali I-Disease 0
syndrome I-Disease 0
may O 0
be O 0
a O 0
common O 0
cause O 0
of O 0
unexplained O 0
hypercalcemia B-Disease 0
and O 0
can O 0
be O 0
precipitated O 0
by O 0
small O 0
amounts O 0
of O 0
orally O 0
ingested O 0
calcium B-Chemical 0
carbonate I-Chemical 0
in O 0
susceptible O 0
persons O 0
. O 0

Treatment O 0
with O 0
hydration O 0
, O 0
furosemide B-Chemical 0
, O 0
and O 0
discontinuation O 0
of O 0
the O 0
calcium B-Chemical 0
and O 0
vitamin B-Chemical 0
D I-Chemical 0
source O 0
is O 0
adequate O 0
. O 0

Pamidronate B-Chemical 0
treatment O 0
is O 0
associated O 0
with O 0
considerable O 0
risk O 0
for O 0
hypocalcemia B-Disease 0
, O 0
even O 0
in O 0
cases O 0
of O 0
initially O 0
severe O 0
hypercalcemia B-Disease 0
. O 0

Warfarin B-Chemical 0
- O 0
induced O 0
leukocytoclastic B-Disease 0
vasculitis I-Disease 0
. O 0

Skin O 0
reactions O 0
associated O 0
with O 0
oral O 0
coumarin B-Chemical 0
- O 0
derived O 0
anticoagulants O 0
are O 0
an O 0
uncommon O 0
occurrence O 0
. O 0

Leukocytoclastic B-Disease 0
vasculitis I-Disease 0
( O 0
LV B-Disease 0
) O 0
is O 0
primarily O 0
a O 0
cutaneous B-Disease 0
small I-Disease 0
vessel I-Disease 0
vasculitis I-Disease 0
, O 0
though O 0
systemic O 0
involvement O 0
may O 0
be O 0
encountered O 0
. O 0

We O 0
report O 0
4 O 0
patients O 0
with O 0
late O 0
- O 0
onset O 0
LV B-Disease 0
probably O 0
due O 0
to O 0
warfarin B-Chemical 0
. O 0

All O 0
4 O 0
patients O 0
presented O 0
with O 0
skin B-Disease 0
eruptions I-Disease 0
that O 0
developed O 0
after O 0
receiving O 0
warfarin B-Chemical 0
for O 0
several O 0
years O 0
. O 0

The O 0
results O 0
of O 0
skin B-Disease 0
lesion I-Disease 0
biopsies O 0
were O 0
available O 0
in O 0
3 O 0
patients O 0
, O 0
confirming O 0
LV B-Disease 0
Cutaneous I-Disease 0
lesions I-Disease 0
resolved O 0
in O 0
all O 0
patients O 0
after O 0
warfarin B-Chemical 0
was O 0
discontinued O 0
. O 0

In O 0
2 O 0
of O 0
the O 0
4 O 0
patients O 0
, O 0
rechallenge O 0
with O 0
warfarin B-Chemical 0
led O 0
to O 0
recurrence O 0
of O 0
the O 0
lesions O 0
. O 0

LV B-Disease 0
may O 0
be O 0
a O 0
late O 0
- O 0
onset O 0
adverse O 0
reaction O 0
associated O 0
with O 0
warfarin B-Chemical 0
therapy O 0
. O 0

Cocaine B-Chemical 0
- O 0
induced O 0
brainstem O 0
seizures B-Disease 0
and O 0
behavior O 0
. O 0

A O 0
variety O 0
of O 0
abnormal O 0
sensory O 0
/ O 0
motor O 0
behaviors O 0
associated O 0
with O 0
electrical O 0
discharges O 0
recorded O 0
from O 0
the O 0
bilateral O 0
brainstem O 0
were O 0
induced O 0
in O 0
adult O 0
WKY O 0
rats O 0
by O 0
mechanical O 0
( O 0
electrode O 0
implants O 0
) O 0
and O 0
DC O 0
electrical O 0
current O 0
stimulations O 0
and O 0
by O 0
acute O 0
and O 0
chronic O 0
administration O 0
of O 0
cocaine B-Chemical 0
. O 0

The O 0
electrode O 0
implant O 0
implicated O 0
one O 0
side O 0
or O 0
the O 0
other O 0
of O 0
the O 0
reticular O 0
system O 0
of O 0
the O 0
brainstem O 0
but O 0
subjects O 0
were O 0
not O 0
incapacitated O 0
by O 0
the O 0
stimulations O 0
. O 0

Cocaine B-Chemical 0
( O 0
40 O 0
mg O 0
/ O 0
kg O 0
) O 0
was O 0
injected O 0
subcutaneously O 0
for O 0
an O 0
acute O 0
experiment O 0
and O 0
subsequent O 0
20 O 0
mg O 0
/ O 0
kg O 0
doses O 0
twice O 0
daily O 0
for O 0
3 O 0
days O 0
in O 0
a O 0
chronic O 0
study O 0
. O 0

Cocaine B-Chemical 0
generated O 0
more O 0
abnormal O 0
behaviors O 0
in O 0
the O 0
brainstem O 0
perturbation O 0
group O 0
, O 0
especially O 0
the O 0
electrically O 0
perturbated O 0
subjects O 0
. O 0

The O 0
abnormal O 0
behaviors O 0
were O 0
yawning O 0
, O 0
retrocollis O 0
, O 0
hyperactivity B-Disease 0
, O 0
hypersensitivity B-Disease 0
, O 0
" O 0
beating O 0
drum O 0
" O 0
behavior O 0
, O 0
squealing O 0
, O 0
head O 0
bobbing O 0
, O 0
circling O 0
, O 0
sniffing O 0
, O 0
abnormal O 0
posturing O 0
, O 0
and O 0
facial O 0
twitching O 0
. O 0

Shifts O 0
in O 0
the O 0
power O 0
frequency O 0
spectra O 0
of O 0
the O 0
discharge O 0
patterns O 0
were O 0
noted O 0
between O 0
quiet O 0
and O 0
pacing O 0
behavioral O 0
states O 0
. O 0

Hypersensitivity B-Disease 0
to O 0
various O 0
auditory O 0
, O 0
tactile O 0
, O 0
and O 0
visual O 0
stimulation O 0
was O 0
present O 0
and O 0
shifts O 0
in O 0
the O 0
brainstem O 0
ambient O 0
power O 0
spectral O 0
frequency O 0
occurred O 0
in O 0
response O 0
to O 0
tactile O 0
stimulation O 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
the O 0
brainstem O 0
generates O 0
and O 0
propagates O 0
pathological O 0
discharges O 0
that O 0
can O 0
be O 0
elicited O 0
by O 0
mechanical O 0
and O 0
DC O 0
electrical O 0
perturbation O 0
. O 0

Cocaine B-Chemical 0
was O 0
found O 0
to O 0
activate O 0
the O 0
discharge O 0
system O 0
and O 0
thus O 0
induce O 0
abnormal O 0
behaviors O 0
that O 0
are O 0
generated O 0
at O 0
the O 0
discharge O 0
site O 0
and O 0
at O 0
distant O 0
sites O 0
to O 0
which O 0
the O 0
discharge O 0
propagates O 0
. O 0

Cognitive O 0
functions O 0
may O 0
also O 0
be O 0
involved O 0
since O 0
dopaminergic O 0
and O 0
serotonergic O 0
cellular O 0
elements O 0
at O 0
the O 0
brainstem O 0
level O 0
are O 0
also O 0
implicated O 0
. O 0

rTMS O 0
of O 0
supplementary O 0
motor O 0
area O 0
modulates O 0
therapy O 0
- O 0
induced O 0
dyskinesias B-Disease 0
in O 0
Parkinson B-Disease 0
disease I-Disease 0
. O 0

The O 0
neural O 0
mechanisms O 0
and O 0
circuitry O 0
involved O 0
in O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesia B-Disease 0
are O 0
unclear O 0
. O 0

Using O 0
repetitive O 0
transcranial O 0
magnetic O 0
stimulation O 0
( O 0
rTMS O 0
) O 0
over O 0
the O 0
supplementary O 0
motor O 0
area O 0
( O 0
SMA O 0
) O 0
in O 0
a O 0
group O 0
of O 0
patients O 0
with O 0
advanced O 0
Parkinson B-Disease 0
disease I-Disease 0
, O 0
the O 0
authors O 0
investigated O 0
whether O 0
modulation O 0
of O 0
SMA O 0
excitability O 0
may O 0
result O 0
in O 0
a O 0
modification O 0
of O 0
a O 0
dyskinetic B-Disease 0
state O 0
induced O 0
by O 0
continuous O 0
apomorphine B-Chemical 0
infusion O 0
. O 0

rTMS O 0
at O 0
1 O 0
Hz O 0
was O 0
observed O 0
to O 0
markedly O 0
reduce O 0
drug B-Disease 0
- I-Disease 0
induced I-Disease 0
dyskinesias I-Disease 0
, O 0
whereas O 0
5 O 0
- O 0
Hz O 0
rTMS O 0
induced O 0
a O 0
slight O 0
but O 0
not O 0
significant O 0
increase O 0
. O 0

Intracavitary O 0
chemotherapy O 0
( O 0
paclitaxel B-Chemical 0
/ O 0
carboplatin B-Chemical 0
liquid O 0
crystalline O 0
cubic O 0
phases O 0
) O 0
for O 0
recurrent O 0
glioblastoma B-Disease 0
- O 0
- O 0
clinical O 0
observations O 0
. O 0

Human O 0
malignant O 0
brain B-Disease 0
tumors I-Disease 0
have O 0
a O 0
poor O 0
prognosis O 0
in O 0
spite O 0
of O 0
surgery O 0
and O 0
radiation O 0
therapy O 0
. O 0

Cubic O 0
phases O 0
consist O 0
of O 0
curved O 0
biocontinuous O 0
lipid O 0
bilayers O 0
, O 0
separating O 0
two O 0
congruent O 0
networks O 0
of O 0
water O 0
channels O 0
. O 0

Used O 0
as O 0
a O 0
host O 0
for O 0
cytotoxic O 0
drugs O 0
, O 0
the O 0
gel O 0
- O 0
like O 0
matrix O 0
can O 0
easily O 0
be O 0
applied O 0
to O 0
the O 0
walls O 0
of O 0
a O 0
surgical O 0
resection O 0
cavity O 0
. O 0

For O 0
human O 0
glioblastoma B-Disease 0
recurrences O 0
, O 0
the O 0
feasibility O 0
, O 0
safety O 0
, O 0
and O 0
short O 0
- O 0
term O 0
effects O 0
of O 0
a O 0
surgical O 0
intracavitary O 0
application O 0
of O 0
paclitaxel B-Chemical 0
and O 0
carboplatin B-Chemical 0
encapsulated O 0
by O 0
liquid O 0
crystalline O 0
cubic O 0
phases O 0
are O 0
examined O 0
in O 0
a O 0
pilot O 0
study O 0
. O 0

A O 0
total O 0
of O 0
12 O 0
patients O 0
with O 0
a O 0
recurrence O 0
of O 0
a O 0
glioblastoma B-Disease 0
multiforme O 0
underwent O 0
re O 0
- O 0
resection O 0
and O 0
received O 0
an O 0
intracavitary O 0
application O 0
of O 0
paclitaxel B-Chemical 0
and O 0
carboplatin B-Chemical 0
cubic O 0
phases O 0
in O 0
different O 0
dosages O 0
. O 0

Six O 0
of O 0
the O 0
patients O 0
received O 0
more O 0
than O 0
15 O 0
mg O 0
paclitaxel B-Chemical 0
and O 0
suffered O 0
from O 0
moderate O 0
to O 0
severe O 0
brain B-Disease 0
edema I-Disease 0
, O 0
while O 0
the O 0
remaining O 0
patients O 0
received O 0
only O 0
a O 0
total O 0
of O 0
15 O 0
mg O 0
paclitaxel B-Chemical 0
. O 0

In O 0
the O 0
latter O 0
group O 0
, O 0
brain B-Disease 0
edema I-Disease 0
was O 0
markedly O 0
reduced O 0
and O 0
dealt O 0
medically O 0
. O 0

Intracavitary O 0
chemotherapy O 0
in O 0
recurrent O 0
glioblastoma B-Disease 0
using O 0
cubic O 0
phases O 0
is O 0
feasible O 0
and O 0
safe O 0
, O 0
yet O 0
the O 0
clinical O 0
benefit O 0
remains O 0
to O 0
be O 0
examined O 0
in O 0
a O 0
clinical O 0
phase O 0
II O 0
study O 0
. O 0

Lamotrigine B-Chemical 0
associated O 0
with O 0
exacerbation O 0
or O 0
de O 0
novo O 0
myoclonus B-Disease 0
in O 0
idiopathic B-Disease 0
generalized I-Disease 0
epilepsies I-Disease 0
. O 0

Five O 0
patients O 0
with O 0
idiopathic B-Disease 0
generalized I-Disease 0
epilepsies I-Disease 0
( O 0
IGE B-Disease 0
) O 0
treated O 0
with O 0
lamotrigine B-Chemical 0
( O 0
LTG B-Chemical 0
) O 0
experienced O 0
exacerbation O 0
or O 0
de O 0
novo O 0
appearance O 0
of O 0
myoclonic B-Disease 0
jerks I-Disease 0
( O 0
MJ B-Disease 0
) O 0
. O 0

In O 0
three O 0
patients O 0
, O 0
LTG B-Chemical 0
exacerbated O 0
MJ B-Disease 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
manner O 0
with O 0
early O 0
aggravation O 0
during O 0
titration O 0
. O 0

MJ B-Disease 0
disappeared O 0
when O 0
LTG B-Chemical 0
dose O 0
was O 0
decreased O 0
by O 0
25 O 0
to O 0
50 O 0
% O 0
. O 0

In O 0
two O 0
patients O 0
, O 0
LTG B-Chemical 0
exacerbated O 0
MJ B-Disease 0
in O 0
a O 0
delayed O 0
but O 0
more O 0
severe O 0
manner O 0
, O 0
with O 0
myoclonic B-Disease 0
status I-Disease 0
that O 0
only O 0
ceased O 0
after O 0
LTG B-Chemical 0
withdrawal O 0
. O 0

Absence O 0
of O 0
acute O 0
cerebral O 0
vasoconstriction O 0
after O 0
cocaine B-Chemical 0
- O 0
associated O 0
subarachnoid B-Disease 0
hemorrhage I-Disease 0
. O 0

INTRODUCTION O 0
: O 0
Cocaine B-Chemical 0
use O 0
has O 0
been O 0
associated O 0
with O 0
neurovascular B-Disease 0
complications I-Disease 0
, O 0
including O 0
arterial O 0
vasoconstriction O 0
and O 0
vasculitis B-Disease 0
. O 0

However O 0
, O 0
there O 0
are O 0
few O 0
studies O 0
of O 0
angiographic O 0
effects O 0
of O 0
cocaine B-Chemical 0
on O 0
human O 0
cerebral O 0
arteries O 0
. O 0

Information O 0
on O 0
these O 0
effects O 0
could O 0
be O 0
obtained O 0
from O 0
angiograms O 0
of O 0
patients O 0
with O 0
cocaine B-Chemical 0
- O 0
associated O 0
subarachnoid B-Disease 0
hemorrhage I-Disease 0
( O 0
SAH B-Disease 0
) O 0
who O 0
underwent O 0
angiography O 0
shortly O 0
after O 0
cocaine B-Chemical 0
use O 0
. O 0

METHODS O 0
: O 0
We O 0
screened O 0
patients O 0
with O 0
SAH B-Disease 0
retrospectively O 0
and O 0
identified O 0
those O 0
with O 0
positive O 0
urine O 0
toxicology O 0
for O 0
cocaine B-Chemical 0
or O 0
its O 0
metabolites O 0
. O 0

Quantitative O 0
arterial O 0
diameter O 0
measurements O 0
from O 0
angiograms O 0
of O 0
these O 0
patients O 0
were O 0
compared O 0
to O 0
measurements O 0
from O 0
control O 0
patients O 0
with O 0
SAH B-Disease 0
who O 0
were O 0
matched O 0
for O 0
factors O 0
known O 0
to O 0
influence O 0
arterial O 0
diameter O 0
. O 0

Qualitative O 0
comparisons O 0
of O 0
small O 0
artery O 0
changes O 0
also O 0
were O 0
made O 0
. O 0

RESULTS O 0
: O 0
Thirteen O 0
patients O 0
with O 0
positive O 0
cocaine B-Chemical 0
toxicology O 0
were O 0
compared O 0
to O 0
26 O 0
controls O 0
. O 0

There O 0
were O 0
no O 0
significant O 0
differences O 0
between O 0
groups O 0
in O 0
the O 0
mean O 0
diameters O 0
of O 0
the O 0
intradural O 0
internal O 0
carotid O 0
, O 0
sphenoidal O 0
segment O 0
of O 0
the O 0
middle O 0
cerebral O 0
, O 0
precommunicating O 0
segment O 0
of O 0
the O 0
anterior O 0
cerebral O 0
, O 0
or O 0
basilar O 0
arteries O 0
( O 0
p O 0
greater O 0
than O 0
0 O 0
. O 0
05 O 0
for O 0
all O 0
comparisons O 0
, O 0
unpaired O 0
t O 0
- O 0
tests O 0
) O 0
. O 0

There O 0
also O 0
were O 0
no O 0
significant O 0
differences O 0
between O 0
groups O 0
when O 0
expressing O 0
diameters O 0
as O 0
the O 0
sum O 0
of O 0
the O 0
precommunicating O 0
segment O 0
of O 0
the O 0
anterior O 0
cerebral O 0
+ O 0
sphenoidal O 0
segment O 0
of O 0
the O 0
middle O 0
cerebral O 0
+ O 0
supraclinoid O 0
internal O 0
carotid O 0
artery O 0
+ O 0
basilar O 0
artery O 0
divided O 0
by O 0
the O 0
diameter O 0
of O 0
the O 0
petrous O 0
internal O 0
carotid O 0
artery O 0
( O 0
p O 0
greater O 0
than O 0
0 O 0
. O 0
05 O 0
, O 0
unpaired O 0
t O 0
- O 0
tests O 0
) O 0
. O 0

Qualitative O 0
assessments O 0
showed O 0
two O 0
arterial O 0
irregularities O 0
in O 0
the O 0
distal O 0
vasculature O 0
in O 0
each O 0
group O 0
. O 0

CONCLUSION O 0
: O 0
No O 0
quantitative O 0
evidence O 0
for O 0
narrowing O 0
of O 0
large O 0
cerebral O 0
arteries O 0
or O 0
qualitative O 0
angiographic O 0
evidence O 0
for O 0
distal O 0
narrowing O 0
or O 0
vasculitis B-Disease 0
could O 0
be O 0
found O 0
in O 0
patients O 0
who O 0
underwent O 0
angiography O 0
after O 0
aneurysmal B-Disease 0
SAH B-Disease 0
associated O 0
with O 0
cocaine B-Chemical 0
use O 0
. O 0

Methamphetamine B-Chemical 0
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Aggressive B-Disease 0
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Herein O 0
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1 O 0
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This O 0
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Analysis O 0
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There O 0
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MEK7 O 0
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These O 0
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Amisulpride B-Chemical 0
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symptoms I-Disease 0
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. O 0

Tic B-Disease 0
disorders I-Disease 0
can O 0
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risperidone B-Chemical 0
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olanzapine B-Chemical 0
and O 0
ziprasidone B-Chemical 0
. O 0

However O 0
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there O 0
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tic B-Disease 0
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symptoms I-Disease 0
, O 0
including O 0
motor O 0
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. O 0

We O 0
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year O 0
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schizophrenic B-Disease 0
who O 0
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involuntary B-Disease 0
eye I-Disease 0
- I-Disease 0
blinking I-Disease 0
movements I-Disease 0
after O 0
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amisulpride B-Chemical 0
treatment O 0
( O 0
1000 O 0
mg O 0
per O 0
day O 0
) O 0
. O 0

The O 0
tic B-Disease 0
- I-Disease 0
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symptoms I-Disease 0
resolved O 0
completely O 0
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we O 0
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. O 0

However O 0
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. O 0

We O 0
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100 O 0
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. O 0

She O 0
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complete O 0
remission O 0
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. O 0

No O 0
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- I-Disease 0
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. O 0

Together O 0
with O 0
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our O 0
patient O 0
suggests O 0
that O 0
tic B-Disease 0
- I-Disease 0
like I-Disease 0
symptoms I-Disease 0
might O 0
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individuals O 0
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treatment O 0
with O 0
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quetiapine B-Chemical 0
, O 0
clozapine B-Chemical 0
, O 0
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amisulpride B-Chemical 0
. O 0

Chloroquine B-Chemical 0
related O 0
complete O 0
heart B-Disease 0
block I-Disease 0
with O 0
blindness B-Disease 0
: O 0
case O 0
report O 0
. O 0

A O 0
27 O 0
- O 0
year O 0
old O 0
African O 0
woman O 0
with O 0
history O 0
of O 0
regular O 0
chloroquine B-Chemical 0
ingestion O 0
presented O 0
with O 0
progressive O 0
deterioration B-Disease 0
of I-Disease 0
vision I-Disease 0
, O 0
easy O 0
fatiguability B-Disease 0
, O 0
dyspnoea B-Disease 0
, O 0
dizziness B-Disease 0
progressing O 0
to O 0
syncopal B-Disease 0
attacks I-Disease 0
. O 0

Ophthalmological O 0
assessment O 0
revealed O 0
features O 0
of O 0
chloroquine B-Chemical 0
retinopathy B-Disease 0
, O 0
cardiac O 0
assessment O 0
revealed O 0
features O 0
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heart B-Disease 0
failure I-Disease 0
and O 0
a O 0
complete O 0
heart B-Disease 0
block I-Disease 0
with O 0
right B-Disease 0
bundle I-Disease 0
branch I-Disease 0
block I-Disease 0
pattern O 0
. O 0

The O 0
heart B-Disease 0
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insertion O 0
and O 0
the O 0
heart B-Disease 0
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resolved O 0
spontaneously O 0
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chloroquine B-Chemical 0
discontinuation O 0
. O 0

She O 0
however O 0
remains O 0
blind B-Disease 0
. O 0

Effects O 0
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on O 0
the O 0
isolated O 0
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. O 0

Although O 0
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has O 0
been O 0
associated O 0
with O 0
the O 0
development O 0
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acute B-Disease 0
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the O 0
mechanism O 0
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. O 0

The O 0
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effects O 0
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15 O 0
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suprofen B-Chemical 0
were O 0
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with O 0
cell O 0
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without O 0
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uric B-Chemical 0
acid I-Chemical 0
. O 0

There O 0
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no O 0
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excretion O 0
, O 0
oxygen B-Chemical 0
consumption O 0
, O 0
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. O 0

In O 0
contrast O 0
, O 0
a O 0
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decline O 0
in O 0
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found O 0
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with O 0
uric B-Chemical 0
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; O 0
no O 0
changes O 0
were O 0
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uric B-Chemical 0
acid I-Chemical 0
. O 0

A O 0
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decrease O 0
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excretion O 0
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uric B-Chemical 0
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was O 0
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. O 0

However O 0
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the O 0
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was O 0
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period O 0
. O 0

In O 0
summary O 0
, O 0
suprofen B-Chemical 0
causes O 0
acute B-Disease 0
declines I-Disease 0
in I-Disease 0
renal I-Disease 0
function I-Disease 0
, O 0
most O 0
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. O 0

Microinjection O 0
of O 0
ritanserin B-Chemical 0
into O 0
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hippocampus O 0
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scopolamine B-Chemical 0
- O 0
induced O 0
amnesia B-Disease 0
in O 0
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. O 0

The O 0
effect O 0
of O 0
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( O 0
5 O 0
- O 0
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) O 0
on O 0
scopolamine B-Chemical 0
( O 0
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) O 0
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in O 0
Morris O 0
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) O 0
was O 0
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. O 0

Rats O 0
were O 0
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into O 0
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of O 0
the O 0
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. O 0

One O 0
week O 0
later O 0
, O 0
they O 0
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vehicles O 0
( O 0
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, O 0
DMSO B-Chemical 0
, O 0
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+ O 0
DMSO B-Chemical 0
) O 0
, O 0
scopolamine B-Chemical 0
( O 0
2 O 0
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/ O 0
0 O 0
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5 O 0
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/ O 0
side O 0
; O 0
30 O 0
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) O 0
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ritanserin B-Chemical 0
( O 0
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4 O 0
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8 O 0
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0 O 0
. O 0
5 O 0
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/ O 0
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) O 0
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scopolamine B-Chemical 0
( O 0
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0 O 0
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+ O 0
ritanserin B-Chemical 0
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0 O 0
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) O 0
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day O 0
. O 0

Animals O 0
were O 0
tested O 0
for O 0
four O 0
consecutive O 0
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. O 0

In O 0
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, O 0
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. O 0

The O 0
results O 0
showed O 0
a O 0
significant O 0
increase O 0
in O 0
escape O 0
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and O 0
traveled O 0
distances O 0
to O 0
find O 0
platform O 0
in O 0
scopolamine B-Chemical 0
- O 0
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as O 0
compared O 0
to O 0
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. O 0

Ritanserin B-Chemical 0
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4 O 0
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0 O 0
. O 0
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) O 0
showed O 0
a O 0
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decrease O 0
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the O 0
mentioned O 0
parameters O 0
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DMSO B-Chemical 0
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. O 0

However O 0
, O 0
scopolamine B-Chemical 0
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ritanserin B-Chemical 0
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resulted O 0
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. O 0

Our O 0
findings O 0
show O 0
that O 0
microinjection O 0
of O 0
ritanserin B-Chemical 0
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the O 0
scopolamine B-Chemical 0
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induced O 0
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. O 0

PTU B-Chemical 0
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vasculitis B-Disease 0
in O 0
a O 0
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Turner B-Disease 0
Syndrome I-Disease 0
and O 0
Graves B-Disease 0
' I-Disease 0
disease I-Disease 0
. O 0

Palpable O 0
purpura B-Disease 0
is O 0
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finding O 0
in O 0
pediatric O 0
patients O 0
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many O 0
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, O 0
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and O 0
autoimmune O 0
processes O 0
. O 0

A O 0
rare O 0
cause O 0
, O 0
drug O 0
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vasculitis B-Disease 0
, O 0
may O 0
result O 0
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the O 0
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of O 0
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) O 0
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response O 0
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. O 0

We O 0
report O 0
a O 0
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with O 0
Turner B-Disease 0
syndrome I-Disease 0
and O 0
Graves B-Disease 0
' I-Disease 0
disease I-Disease 0
who O 0
presented O 0
with O 0
palpable O 0
purpuric B-Disease 0
lesions I-Disease 0
. O 0

The O 0
diagnosis O 0
of O 0
propylthiouracil B-Chemical 0
( O 0
PTU B-Chemical 0
) O 0
- O 0
associated O 0
vasculitis B-Disease 0
was O 0
made O 0
by O 0
observation O 0
of O 0
consistent O 0
clinical O 0
features O 0
, O 0
the O 0
detection O 0
of O 0
elevated O 0
ANA O 0
and O 0
ANCA O 0
in O 0
the O 0
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, O 0
and O 0
the O 0
observed O 0
clinical O 0
resolution O 0
of O 0
symptoms O 0
following O 0
withdrawal O 0
of O 0
PTU B-Chemical 0
. O 0

Subsequent O 0
treatment O 0
of O 0
persistent O 0
hyperthyroidism B-Disease 0
with O 0
radioablation O 0
did O 0
not O 0
result O 0
in O 0
an O 0
exacerbation O 0
of O 0
the O 0
vasculitis B-Disease 0
, O 0
a O 0
complication O 0
described O 0
in O 0
prior O 0
case O 0
reports O 0
. O 0

Daidzein B-Chemical 0
activates O 0
choline B-Chemical 0
acetyltransferase O 0
from O 0
MC O 0
- O 0
IXC O 0
cells O 0
and O 0
improves O 0
drug O 0
- O 0
induced O 0
amnesia B-Disease 0
. O 0

The O 0
choline B-Chemical 0
acetyltransferase O 0
( O 0
ChAT O 0
) O 0
activator O 0
, O 0
which O 0
enhances O 0
cholinergic O 0
transmission O 0
via O 0
an O 0
augmentation O 0
of O 0
the O 0
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production O 0
of O 0
acetylcholine B-Chemical 0
( O 0
ACh B-Chemical 0
) O 0
, O 0
is O 0
an O 0
important O 0
factor O 0
in O 0
the O 0
treatment O 0
of O 0
Alzheimer B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
( O 0
AD B-Disease 0
) O 0
. O 0

Methanolic O 0
extracts O 0
from O 0
Pueraria O 0
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exhibited O 0
an O 0
activation O 0
effect O 0
( O 0
46 O 0
% O 0
) O 0
on O 0
ChAT O 0
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. O 0

Via O 0
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Pueraria O 0
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identified O 0
as O 0
daidzein B-Chemical 0
( O 0
4 B-Chemical 0
' I-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
dihydroxy I-Chemical 0
- I-Chemical 0
isoflavone I-Chemical 0
) O 0
. O 0

In O 0
order O 0
to O 0
investigate O 0
the O 0
effects O 0
of O 0
daidzein B-Chemical 0
from O 0
Pueraria O 0
thunbergiana O 0
on O 0
scopolamine B-Chemical 0
- O 0
induced O 0
impairments B-Disease 0
of I-Disease 0
learning I-Disease 0
and I-Disease 0
memory I-Disease 0
, O 0
we O 0
conducted O 0
a O 0
series O 0
of O 0
in O 0
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tests O 0
. O 0

Administration O 0
of O 0
daidzein B-Chemical 0
( O 0
4 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
) O 0
to O 0
mice O 0
was O 0
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significantly O 0
to O 0
reverse O 0
scopolamine B-Chemical 0
- O 0
induced O 0
amnesia B-Disease 0
, O 0
according O 0
to O 0
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a O 0
Y O 0
- O 0
maze O 0
test O 0
. O 0

Injections O 0
of O 0
scopolamine B-Chemical 0
into O 0
mice O 0
resulted O 0
in O 0
impaired O 0
performance O 0
on O 0
Y O 0
- O 0
maze O 0
tests O 0
( O 0
a O 0
37 O 0
% O 0
decreases O 0
in O 0
alternation O 0
behavior O 0
) O 0
. O 0

By O 0
way O 0
of O 0
contrast O 0
, O 0
mice O 0
treated O 0
with O 0
daidzein B-Chemical 0
prior O 0
to O 0
the O 0
scopolamine B-Chemical 0
injections O 0
were O 0
noticeably O 0
protected O 0
from O 0
this O 0
performance O 0
impairment O 0
( O 0
an O 0
approximately O 0
12 O 0
% O 0
- O 0
21 O 0
% O 0
decrease O 0
in O 0
alternation O 0
behavior O 0
) O 0
. O 0

These O 0
results O 0
indicate O 0
that O 0
daidzein B-Chemical 0
might O 0
play O 0
a O 0
role O 0
in O 0
acetylcholine B-Chemical 0
biosynthesis O 0
as O 0
a O 0
ChAT O 0
activator O 0
, O 0
and O 0
that O 0
it O 0
also O 0
ameliorates O 0
scopolamine B-Chemical 0
- O 0
induced O 0
amnesia B-Disease 0
. O 0

Urinary O 0
symptoms O 0
and O 0
quality O 0
of O 0
life O 0
changes O 0
in O 0
Thai O 0
women O 0
with O 0
overactive B-Disease 0
bladder I-Disease 0
after O 0
tolterodine B-Chemical 0
treatment O 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
study O 0
the O 0
urinary O 0
symptoms O 0
and O 0
quality O 0
of O 0
life O 0
changes O 0
in O 0
Thai O 0
women O 0
with O 0
overactive B-Disease 0
bladder I-Disease 0
( O 0
OAB B-Disease 0
) O 0
after O 0
tolterodine B-Chemical 0
treatment O 0
. O 0

MATERIAL O 0
AND O 0
METHOD O 0
: O 0
Thirty O 0
women O 0
( O 0
aged O 0
30 O 0
- O 0
77 O 0
years O 0
) O 0
diagnosed O 0
as O 0
having O 0
OAB B-Disease 0
at O 0
the O 0
Gynecology O 0
Clinic O 0
, O 0
King O 0
Chulalongkorn O 0
Memorial O 0
Hospital O 0
from O 0
January O 0
to O 0
April O 0
2004 O 0
were O 0
included O 0
in O 0
the O 0
present O 0
study O 0
. O 0

Tolterodine B-Chemical 0
2 O 0
mg O 0
, O 0
twice O 0
daily O 0
was O 0
given O 0
. O 0

After O 0
8 O 0
weeks O 0
treatment O 0
, O 0
changes O 0
in O 0
micturition O 0
diary O 0
variables O 0
and O 0
tolerability O 0
were O 0
determined O 0
. O 0

Short O 0
form O 0
36 O 0
( O 0
SF36 O 0
) O 0
questionaires O 0
( O 0
Thai O 0
version O 0
) O 0
were O 0
given O 0
before O 0
and O 0
after O 0
8 O 0
weeks O 0
of O 0
treatment O 0
. O 0

RESULTS O 0
: O 0
At O 0
8 O 0
weeks O 0
, O 0
all O 0
micturition O 0
per O 0
day O 0
decreased O 0
from O 0
16 O 0
. O 0

7 O 0
+ O 0
/ O 0
- O 0
5 O 0
. O 0

3 O 0
to O 0
6 O 0
. O 0

7 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
4 O 0
times O 0
per O 0
day O 0
. O 0

The O 0
number O 0
of O 0
nocturia B-Disease 0
episodes O 0
decreased O 0
from O 0
5 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
2 O 0
to O 0
1 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
0 O 0
times O 0
per O 0
night O 0
. O 0

The O 0
most O 0
common O 0
side O 0
effect O 0
was O 0
dry B-Disease 0
month I-Disease 0
in O 0
5 O 0
cases O 0
( O 0
16 O 0
. O 0
7 O 0
% O 0
) O 0
with O 0
2 O 0
cases O 0
reporting O 0
a O 0
moderate O 0
degree O 0
and O 0
1 O 0
case O 0
with O 0
severe O 0
degree O 0
. O 0

Only O 0
one O 0
case O 0
( O 0
3 O 0
. O 0
3 O 0
% O 0
) O 0
withdrew O 0
from O 0
the O 0
present O 0
study O 0
due O 0
to O 0
a O 0
severe O 0
dry B-Disease 0
mouth I-Disease 0
. O 0

The O 0
SF O 0
- O 0
36 O 0
scores O 0
changed O 0
significantly O 0
in O 0
the O 0
domains O 0
of O 0
physical O 0
functioning O 0
, O 0
role O 0
function O 0
emotional O 0
, O 0
social O 0
function O 0
and O 0
mental O 0
heath O 0
. O 0

CONCLUSION O 0
: O 0
Tolterodine B-Chemical 0
was O 0
well O 0
tolerated O 0
and O 0
its O 0
effects O 0
improved O 0
the O 0
quality O 0
of O 0
life O 0
in O 0
Thai O 0
women O 0
with O 0
OAB B-Disease 0
. O 0

Remifentanil B-Chemical 0
pretreatment O 0
reduces O 0
myoclonus B-Disease 0
after O 0
etomidate B-Chemical 0
. O 0

STUDY O 0
OBJECTIVE 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
compare O 0
the O 0
effect O 0
of O 0
pretreatment O 0
with O 0
remifentanil B-Chemical 0
1 O 0
microg O 0
/ O 0
kg O 0
and O 0
the O 0
effect O 0
of O 0
gender O 0
on O 0
the O 0
incidence O 0
of O 0
myoclonus B-Disease 0
after O 0
anesthesia O 0
induction O 0
with O 0
etomidate B-Chemical 0
. O 0

DESIGN O 0
: O 0
This O 0
was O 0
a O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
study O 0
. O 0

SETTING O 0
: O 0
The O 0
study O 0
was O 0
conducted O 0
at O 0
a O 0
university O 0
hospital O 0
. O 0

PATIENTS O 0
: O 0
Sixty O 0
patients O 0
were O 0
pretreated O 0
in O 0
a O 0
randomized O 0
double O 0
- O 0
blinded O 0
fashion O 0
with O 0
remifentanil B-Chemical 0
1 O 0
microg O 0
/ O 0
kg O 0
or O 0
placebo O 0
. O 0

Two O 0
minutes O 0
after O 0
remifentanil B-Chemical 0
or O 0
placebo O 0
injection O 0
, O 0
etomidate B-Chemical 0
0 O 0
. O 0
3 O 0
mg O 0
/ O 0
kg O 0
was O 0
given O 0
. O 0

MEASUREMENTS O 0
: O 0
Myoclonus B-Disease 0
was O 0
recorded O 0
with O 0
a O 0
scale O 0
of O 0
0 O 0
to O 0
3 O 0
. O 0

The O 0
grade O 0
of O 0
sedation O 0
( O 0
none O 0
, O 0
mild O 0
, O 0
moderate O 0
, O 0
severe O 0
) O 0
, O 0
nausea B-Disease 0
, O 0
pruritus B-Disease 0
, O 0
and O 0
apnea B-Disease 0
were O 0
recorded O 0
after O 0
injection O 0
of O 0
both O 0
drugs O 0
. O 0

MAIN O 0
RESULTS O 0
: O 0
The O 0
incidence O 0
of O 0
myoclonus B-Disease 0
was O 0
significantly O 0
lower O 0
in O 0
the O 0
remifentanil B-Chemical 0
group O 0
( O 0
6 O 0
. O 0
7 O 0
% O 0
) O 0
than O 0
in O 0
the O 0
placebo O 0
group O 0
( O 0
70 O 0
% O 0
) O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

None O 0
of O 0
the O 0
patients O 0
experienced O 0
sedation O 0
, O 0
apnea B-Disease 0
, O 0
nausea B-Disease 0
, O 0
or O 0
pruritus B-Disease 0
after O 0
injection O 0
of O 0
both O 0
drugs O 0
. O 0

In O 0
the O 0
placebo O 0
group O 0
, O 0
male O 0
patients O 0
were O 0
associated O 0
with O 0
significantly O 0
increased O 0
incidence O 0
of O 0
myoclonus B-Disease 0
after O 0
etomidate B-Chemical 0
administration O 0
. O 0

CONCLUSION O 0
: O 0
Pretreatment O 0
with O 0
remifentanil B-Chemical 0
1 O 0
microg O 0
/ O 0
kg O 0
reduced O 0
myoclonus B-Disease 0
after O 0
etomidate B-Chemical 0
induction O 0
without O 0
side O 0
effects O 0
such O 0
as O 0
sedation O 0
, O 0
apnea B-Disease 0
, O 0
nausea B-Disease 0
, O 0
or O 0
pruritus B-Disease 0
. O 0

Men O 0
experience O 0
increased O 0
incidence O 0
of O 0
myoclonus B-Disease 0
than O 0
women O 0
after O 0
etomidate B-Chemical 0
administration O 0
. O 0

Memory O 0
function O 0
and O 0
serotonin B-Chemical 0
transporter O 0
promoter O 0
gene O 0
polymorphism O 0
in O 0
ecstasy B-Chemical 0
( O 0
MDMA B-Chemical 0
) O 0
users O 0
. O 0

Although 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
or O 0
ecstasy B-Chemical 0
) O 0
has O 0
been O 0
shown O 0
to O 0
damage O 0
brain O 0
serotonin B-Chemical 0
( O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
) O 0
neurons O 0
in O 0
animals O 0
and O 0
possibly O 0
humans O 0
, O 0
little O 0
is O 0
known O 0
about O 0
the O 0
long O 0
- O 0
term O 0
consequences O 0
of O 0
MDMA B-Chemical 0
- O 0
induced O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
neurotoxic B-Disease 0
lesions I-Disease 0
on O 0
functions O 0
in O 0
which O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
is O 0
involved O 0
, O 0
such O 0
as O 0
cognitive O 0
function O 0
. O 0

Because O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
transporters O 0
play O 0
a O 0
key O 0
element O 0
in O 0
the O 0
regulation O 0
of O 0
synaptic O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
transmission O 0
it O 0
may O 0
be O 0
important O 0
to O 0
control O 0
for O 0
the O 0
potential O 0
covariance O 0
effect O 0
of O 0
a O 0
polymorphism O 0
in O 0
the O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
transporter O 0
promoter O 0
gene O 0
region O 0
( O 0
5 O 0
- O 0
HTTLPR O 0
) O 0
when O 0
studying O 0
the O 0
effects O 0
of O 0
MDMA B-Chemical 0
as O 0
well O 0
as O 0
cognitive O 0
functioning 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
effects O 0
of O 0
moderate O 0
and O 0
heavy O 0
MDMA B-Chemical 0
use O 0
on O 0
cognitive O 0
function O 0
, O 0
as O 0
well O 0
as O 0
the O 0
effects O 0
of O 0
long O 0
- O 0
term O 0
abstention O 0
from O 0
MDMA B-Chemical 0
, O 0
in O 0
subjects O 0
genotyped O 0
for O 0
5 O 0
- O 0
HTTLPR O 0
. O 0

A O 0
second O 0
aim O 0
of O 0
the O 0
study O 0
was O 0
to O 0
determine O 0
whether O 0
these O 0
effects O 0
differ O 0
for O 0
females O 0
and O 0
males O 0
. O 0

Fifteen O 0
moderate O 0
MDMA B-Chemical 0
users O 0
( O 0
< O 0
55 O 0
lifetime O 0
tablets O 0
) O 0
, O 0
22 O 0
heavy O 0
MDMA B-Chemical 0
+ O 0
users O 0
( O 0
> O 0
55 O 0
lifetime O 0
tablets O 0
) O 0
, O 0
16 O 0
ex O 0
- O 0
MDMA B-Chemical 0
+ O 0
users O 0
( O 0
last O 0
tablet O 0
> O 0
1 O 0
year O 0
ago O 0
) O 0
and O 0
13 O 0
controls O 0
were O 0
compared O 0
on O 0
a O 0
battery O 0
of O 0
neuropsychological O 0
tests O 0
. O 0

DNA O 0
from O 0
peripheral O 0
nuclear O 0
blood O 0
cells O 0
was O 0
genotyped O 0
for O 0
5 O 0
- O 0
HTTLPR O 0
using O 0
standard O 0
polymerase O 0
chain O 0
reaction O 0
methods O 0
. O 0
A O 0
significant O 0
group O 0
effect O 0
was O 0
observed O 0
only O 0
on O 0
memory O 0
function O 0
tasks O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
04 O 0
) O 0
but O 0
not O 0
on O 0
reaction O 0
times O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
61 O 0
) O 0
or O 0
attention O 0
/ O 0
executive O 0
functioning O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
59 O 0
) O 0
. O 0

Heavy O 0
and O 0
ex O 0
- O 0
MDMA B-Chemical 0
+ O 0
users O 0
performed O 0
significantly O 0
poorer O 0
on O 0
memory O 0
tasks O 0
than O 0
controls O 0
. O 0

In O 0
contrast O 0
, O 0
no O 0
evidence O 0
of O 0
memory B-Disease 0
impairment I-Disease 0
was O 0
observed O 0
in O 0
moderate O 0
MDMA B-Chemical 0
users O 0
. O 0

No O 0
significant O 0
effect O 0
of O 0
5 O 0
- O 0
HTTLPR O 0
or O 0
gender O 0
was O 0
observed O 0
. O 0

While O 0
the O 0
use O 0
of O 0
MDMA B-Chemical 0
in O 0
quantities O 0
that O 0
may O 0
be O 0
considered O 0
" O 0
moderate O 0
" O 0
is O 0
not O 0
associated O 0
with O 0
impaired B-Disease 0
memory I-Disease 0
functioning I-Disease 0
, O 0
heavy O 0
use O 0
of O 0
MDMA B-Chemical 0
use O 0
may O 0
lead O 0
to O 0
long O 0
lasting O 0
memory B-Disease 0
impairments I-Disease 0
. O 0

No O 0
effect O 0
of O 0
5 O 0
- O 0
HTTLPR O 0
or O 0
gender O 0
on O 0
memory O 0
function O 0
or O 0
MDMA B-Chemical 0
use O 0
was O 0
observed O 0
. O 0

Role O 0
of O 0
mangiferin B-Chemical 0
on O 0
biochemical O 0
alterations O 0
and O 0
antioxidant O 0
status O 0
in 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
. O 0

The O 0
current O 0
study O 0
dealt O 0
with O 0
the O 0
protective O 0
role O 0
of O 0
mangiferin B-Chemical 0
, O 0
a O 0
polyphenol B-Chemical 0
from O 0
Mangifera O 0
indica O 0
Linn O 0
. O 0

( O 0
Anacardiaceae O 0
) O 0
, O 0
on O 0
isoproterenol B-Chemical 0
( O 0
ISPH B-Chemical 0
) O 0
- O 0
induced O 0
myocardial B-Disease 0
infarction I-Disease 0
( O 0
MI B-Disease 0
) O 0
in O 0
rats O 0
through O 0
its O 0
antioxidative O 0
mechanism O 0
. O 0

Subcutaneous O 0
injection O 0
of O 0
ISPH B-Chemical 0
( O 0
200 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
in O 0
1 O 0
ml O 0
saline O 0
) O 0
to O 0
rats O 0
for O 0
2 O 0
consecutive O 0
days O 0
caused O 0
myocardial B-Disease 0
damage I-Disease 0
in O 0
rat O 0
heart O 0
, O 0
which O 0
was O 0
determined O 0
by O 0
the O 0
increased O 0
activity O 0
of O 0
serum O 0
lactate B-Chemical 0
dehydrogenase O 0
( O 0
LDH O 0
) O 0
and O 0
creatine B-Chemical 0
phosphokinase O 0
isoenzymes O 0
( O 0
CK O 0
- O 0
MB O 0
) O 0
, O 0
increased O 0
uric B-Chemical 0
acid I-Chemical 0
level O 0
and O 0
reduced O 0
plasma O 0
iron B-Chemical 0
binding O 0
capacity O 0
. O 0

The O 0
protective O 0
role O 0
of O 0
mangiferin B-Chemical 0
was O 0
analyzed O 0
by O 0
triphenyl B-Chemical 0
tetrazolium I-Chemical 0
chloride I-Chemical 0
( O 0
TTC B-Chemical 0
) O 0
test O 0
used O 0
for O 0
macroscopic O 0
enzyme O 0
mapping O 0
assay O 0
of O 0
the O 0
ischemic B-Disease 0
myocardium I-Disease 0
. O 0

The O 0
heart O 0
tissue O 0
antioxidant O 0
enzymes O 0
such O 0
as O 0
superoxide B-Chemical 0
dismutase O 0
, O 0
catalase O 0
, O 0
glutathione B-Chemical 0
peroxidase O 0
, O 0
glutathione B-Chemical 0
transferase O 0
and O 0
glutathione B-Chemical 0
reductase O 0
activities O 0
, O 0
non O 0
- O 0
enzymic O 0
antioxidants O 0
such O 0
as O 0
cerruloplasmin O 0
, O 0
Vitamin B-Chemical 0
C I-Chemical 0
, O 0
Vitamin B-Chemical 0
E I-Chemical 0
and O 0
glutathione B-Chemical 0
levels O 0
were O 0
altered O 0
in O 0
MI B-Disease 0
rats O 0
. O 0

Upon O 0
pretreatment O 0
with O 0
mangiferin B-Chemical 0
( O 0
100 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
suspended O 0
in O 0
2 O 0
ml O 0
of O 0
dimethyl B-Chemical 0
sulphoxide I-Chemical 0
) O 0
given O 0
intraperitoneally O 0
for O 0
28 O 0
days O 0
to O 0
MI B-Disease 0
rats O 0
protected O 0
the O 0
above O 0
- O 0
mentioned O 0
parameters O 0
to O 0
fall O 0
from O 0
the O 0
normal O 0
levels O 0
. O 0

Activities O 0
of O 0
heart O 0
tissue O 0
enzymic O 0
antioxidants O 0
and O 0
serum O 0
non O 0
- O 0
enzymic O 0
antioxidants O 0
levels O 0
rose O 0
significantly O 0
upon O 0
mangiferin B-Chemical 0
administration O 0
as O 0
compared O 0
to O 0
ISPH B-Chemical 0
- O 0
induced O 0
MI B-Disease 0
rats O 0
. O 0

From O 0
the O 0
present O 0
study O 0
it O 0
is O 0
concluded O 0
that O 0
mangiferin B-Chemical 0
exerts O 0
a O 0
beneficial O 0
effect O 0
against O 0
ISPH B-Chemical 0
- O 0
induced O 0
MI B-Disease 0
due O 0
to O 0
its O 0
antioxidant O 0
potential O 0
, O 0
which O 0
regulated O 0
the O 0
tissues O 0
defense O 0
system O 0
against O 0
cardiac B-Disease 0
damage I-Disease 0
. O 0

Cardiovascular O 0
risk O 0
with O 0
cyclooxygenase B-Chemical 0
inhibitors I-Chemical 0
: O 0
general O 0
problem O 0
with O 0
substance O 0
specific O 0
differences O 0
? O 0

Randomised O 0
clinical O 0
trials O 0
and O 0
observational O 0
studies O 0
have O 0
shown O 0
an O 0
increased O 0
risk O 0
of O 0
myocardial B-Disease 0
infarction I-Disease 0
, O 0
stroke B-Disease 0
, O 0
hypertension B-Disease 0
and O 0
heart B-Disease 0
failure I-Disease 0
during O 0
treatment O 0
with O 0
cyclooxygenase B-Chemical 0
inhibitors I-Chemical 0
. O 0

Adverse O 0
cardiovascular O 0
effects O 0
occurred O 0
mainly O 0
, O 0
but O 0
not O 0
exclusively O 0
, O 0
in O 0
patients O 0
with O 0
concomitant O 0
risk O 0
factors O 0
. O 0

Cyclooxygenase B-Chemical 0
inhibitors I-Chemical 0
cause O 0
complex O 0
changes O 0
in O 0
renal O 0
, O 0
vascular O 0
and O 0
cardiac O 0
prostanoid O 0
profiles O 0
thereby O 0
increasing O 0
vascular O 0
resistance O 0
and O 0
fluid O 0
retention O 0
. O 0

The O 0
incidence O 0
of O 0
cardiovascular O 0
adverse O 0
events O 0
tends O 0
to O 0
increase O 0
with O 0
the O 0
daily O 0
dose O 0
and O 0
total O 0
exposure O 0
time O 0
. O 0

A O 0
comparison O 0
of O 0
individual O 0
selective O 0
and O 0
unselective O 0
cyclooxygenase B-Chemical 0
inhibitors I-Chemical 0
suggests O 0
substance O 0
- O 0
specific O 0
differences O 0
, O 0
which O 0
may O 0
depend O 0
on O 0
differences O 0
in O 0
pharmacokinetic O 0
parameters O 0
or O 0
inhibitory O 0
potency O 0
and O 0
may O 0
be O 0
contributed O 0
by O 0
prostaglandin B-Chemical 0
- O 0
independent O 0
effects O 0
. O 0

Diagnostic O 0
markers O 0
such O 0
as O 0
N B-Chemical 0
- I-Chemical 0
terminal I-Chemical 0
pro I-Chemical 0
brain I-Chemical 0
natriuretic I-Chemical 0
peptide I-Chemical 0
( O 0
NT B-Chemical 0
- I-Chemical 0
proBNP I-Chemical 0
) O 0
or O 0
high O 0
- O 0
sensitive O 0
C O 0
- O 0
reactive O 0
protein O 0
might O 0
help O 0
in O 0
the O 0
early O 0
identification O 0
of O 0
patients O 0
at O 0
risk O 0
, O 0
thus O 0
avoiding O 0
the O 0
occurrence O 0
of O 0
serious O 0
cardiovascular B-Disease 0
toxicity I-Disease 0
. O 0

Pilocarpine B-Chemical 0
seizures B-Disease 0
cause O 0
age O 0
- O 0
dependent O 0
impairment B-Disease 0
in I-Disease 0
auditory I-Disease 0
location I-Disease 0
discrimination I-Disease 0
. O 0

Children O 0
who O 0
have O 0
status B-Disease 0
epilepticus I-Disease 0
have O 0
continuous O 0
or O 0
rapidly O 0
repeating O 0
seizures B-Disease 0
that O 0
may O 0
be O 0
life O 0
- O 0
threatening O 0
and O 0
may O 0
cause O 0
life O 0
- O 0
long O 0
changes O 0
in O 0
brain O 0
and O 0
behavior O 0
. O 0

The O 0
extent O 0
to O 0
which O 0
status B-Disease 0
epilepticus I-Disease 0
causes O 0
deficits B-Disease 0
in I-Disease 0
auditory I-Disease 0
discrimination I-Disease 0
is O 0
unknown O 0
. O 0

A O 0
naturalistic O 0
auditory O 0
location O 0
discrimination O 0
method O 0
was O 0
used O 0
to O 0
evaluate O 0
this O 0
question O 0
using O 0
an O 0
animal O 0
model O 0
of O 0
status B-Disease 0
epilepticus I-Disease 0
. O 0

Male O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
were O 0
injected O 0
with O 0
saline O 0
on O 0
postnatal O 0
day O 0
( O 0
P O 0
) O 0
20 O 0
, O 0
or O 0
a O 0
convulsant O 0
dose O 0
of O 0
pilocarpine B-Chemical 0
on O 0
P20 O 0
or O 0
P45 O 0
. O 0

Pilocarpine B-Chemical 0
on O 0
either O 0
day O 0
induced O 0
status B-Disease 0
epilepticus I-Disease 0
; O 0
status B-Disease 0
epilepticus I-Disease 0
at O 0
P45 O 0
resulted O 0
in O 0
CA3 O 0
cell O 0
loss O 0
and O 0
spontaneous O 0
seizures B-Disease 0
, O 0
whereas O 0
P20 O 0
rats O 0
had O 0
no O 0
cell O 0
loss O 0
or O 0
spontaneous O 0
seizures B-Disease 0
. O 0

Mature O 0
rats O 0
were O 0
trained O 0
with O 0
sound O 0
- O 0
source O 0
location O 0
and O 0
sound O 0
- O 0
silence O 0
discriminations O 0
. O 0

Control O 0
( O 0
saline O 0
P20 O 0
) O 0
rats O 0
acquired O 0
both O 0
discriminations O 0
immediately O 0
. O 0

In O 0
status B-Disease 0
epilepticus I-Disease 0
( O 0
P20 O 0
) O 0
rats O 0
, O 0
acquisition O 0
of O 0
the O 0
sound O 0
- O 0
source O 0
location O 0
discrimination O 0
was O 0
moderately O 0
impaired O 0
. O 0

Status B-Disease 0
epilepticus I-Disease 0
( O 0
P45 O 0
) O 0
rats O 0
failed O 0
to O 0
acquire O 0
either O 0
sound O 0
- O 0
source O 0
location O 0
or O 0
sound O 0
- O 0
silence O 0
discriminations O 0
. O 0

Status B-Disease 0
epilepticus I-Disease 0
in O 0
rat O 0
causes O 0
an O 0
age O 0
- O 0
dependent O 0
, O 0
long O 0
- O 0
term O 0
impairment B-Disease 0
in I-Disease 0
auditory I-Disease 0
discrimination I-Disease 0
. O 0

This O 0
impairment O 0
may O 0
explain O 0
one O 0
cause O 0
of O 0
impaired B-Disease 0
auditory I-Disease 0
location I-Disease 0
discrimination I-Disease 0
in O 0
humans O 0
. O 0

Nerve O 0
growth O 0
factor O 0
and O 0
prostaglandins B-Chemical 0
in O 0
the O 0
urine O 0
of O 0
female O 0
patients O 0
with O 0
overactive B-Disease 0
bladder I-Disease 0
. O 0

PURPOSE O 0
: O 0
NGF O 0
and O 0
PGs B-Chemical 0
in O 0
the O 0
bladder O 0
can O 0
be O 0
affected O 0
by O 0
pathological O 0
changes O 0
in O 0
the O 0
bladder O 0
and O 0
these O 0
changes O 0
can O 0
be O 0
detected O 0
in O 0
urine O 0
. O 0

We O 0
investigated O 0
changes O 0
in O 0
urinary O 0
NGF O 0
and O 0
PGs B-Chemical 0
in O 0
women O 0
with O 0
OAB B-Disease 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
The O 0
study O 0
groups O 0
included O 0
65 O 0
women O 0
with O 0
OAB B-Disease 0
and O 0
20 O 0
without O 0
bladder O 0
symptoms O 0
who O 0
served O 0
as O 0
controls O 0
. O 0

Evaluation O 0
included O 0
patient O 0
history O 0
, O 0
urinalysis O 0
, O 0
a O 0
voiding O 0
diary O 0
and O 0
urodynamic O 0
studies O 0
. O 0

Urine O 0
samples O 0
were O 0
collected O 0
. O 0

NGF O 0
, O 0
PGE2 B-Chemical 0
, O 0
PGF2alpha B-Chemical 0
and O 0
PGI2 B-Chemical 0
were O 0
measured O 0
using O 0
enzyme O 0
- O 0
linked O 0
immunosorbent O 0
assay O 0
and O 0
compared O 0
between O 0
the O 0
groups O 0
. O 0

In O 0
addition O 0
, O 0
correlations O 0
between O 0
urinary O 0
NGF O 0
and O 0
PG B-Chemical 0
, O 0
and O 0
urodynamic O 0
parameters O 0
in O 0
patients O 0
with O 0
OAB B-Disease 0
were O 0
examined O 0
. O 0

RESULTS O 0
: O 0
Urinary O 0
NGF O 0
, O 0
PGE2 B-Chemical 0
and O 0
PGF2alpha B-Chemical 0
were O 0
significantly O 0
increased O 0
in O 0
patients O 0
with O 0
OAB B-Disease 0
compared O 0
with O 0
controls O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

However O 0
, O 0
urinary O 0
PGI2 B-Chemical 0
was O 0
not O 0
different O 0
between O 0
controls O 0
and O 0
patients O 0
with O 0
OAB B-Disease 0
. O 0

In O 0
patients O 0
with O 0
OAB B-Disease 0
urinary O 0
PGE2 B-Chemical 0
positively O 0
correlated O 0
with O 0
volume O 0
at O 0
first O 0
desire O 0
to O 0
void O 0
and O 0
maximum O 0
cystometric O 0
capacity O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Urinary O 0
NGF O 0
, O 0
PGF2alpha B-Chemical 0
and O 0
PGI2 B-Chemical 0
did O 0
not O 0
correlate O 0
with O 0
urodynamic O 0
parameters O 0
in O 0
patients O 0
with O 0
OAB B-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
NGF O 0
and O 0
PGs B-Chemical 0
have O 0
important O 0
roles O 0
in O 0
the O 0
development O 0
of O 0
OAB B-Disease 0
symptoms O 0
in O 0
female O 0
patients O 0
. O 0

Urinary O 0
levels O 0
of O 0
these O 0
factors O 0
may O 0
be O 0
used O 0
as O 0
markers O 0
to O 0
evaluate O 0
OAB B-Disease 0
symptoms O 0
. O 0

Definition O 0
and O 0
management O 0
of O 0
anemia B-Disease 0
in O 0
patients O 0
infected B-Disease 0
with I-Disease 0
hepatitis I-Disease 0
C I-Disease 0
virus I-Disease 0
. O 0

Chronic B-Disease 0
infection I-Disease 0
with I-Disease 0
hepatitis I-Disease 0
C I-Disease 0
virus I-Disease 0
( O 0
HCV O 0
) O 0
can O 0
progress O 0
to O 0
cirrhosis B-Disease 0
, O 0
hepatocellular B-Disease 0
carcinoma I-Disease 0
, O 0
and O 0
end B-Disease 0
- I-Disease 0
stage I-Disease 0
liver I-Disease 0
disease I-Disease 0
. O 0

The O 0
current O 0
best O 0
treatment O 0
for O 0
HCV B-Disease 0
infection I-Disease 0
is O 0
combination O 0
therapy O 0
with O 0
pegylated O 0
interferon B-Chemical 0
and O 0
ribavirin B-Chemical 0
. O 0

Although O 0
this O 0
regimen O 0
produces O 0
sustained O 0
virologic O 0
responses O 0
( O 0
SVRs O 0
) O 0
in O 0
approximately O 0
50 O 0
% O 0
of O 0
patients O 0
, O 0
it O 0
can O 0
be O 0
associated O 0
with O 0
a O 0
potentially O 0
dose O 0
- O 0
limiting O 0
hemolytic B-Disease 0
anemia I-Disease 0
. O 0

Hemoglobin O 0
concentrations O 0
decrease O 0
mainly O 0
as O 0
a O 0
result O 0
of O 0
ribavirin B-Chemical 0
- O 0
induced O 0
hemolysis B-Disease 0
, O 0
and O 0
this O 0
anemia B-Disease 0
can O 0
be O 0
problematic O 0
in O 0
patients O 0
with O 0
HCV B-Disease 0
infection I-Disease 0
, O 0
especially O 0
those O 0
who O 0
have O 0
comorbid O 0
renal B-Disease 0
or I-Disease 0
cardiovascular I-Disease 0
disorders I-Disease 0
. O 0

In O 0
general O 0
, O 0
anemia B-Disease 0
can O 0
increase O 0
the O 0
risk O 0
of O 0
morbidity O 0
and O 0
mortality O 0
, O 0
and O 0
may O 0
have O 0
negative O 0
effects O 0
on O 0
cerebral O 0
function O 0
and O 0
quality O 0
of O 0
life O 0
. O 0

Although O 0
ribavirin B-Chemical 0
- O 0
associated O 0
anemia B-Disease 0
can O 0
be O 0
reversed O 0
by O 0
dose O 0
reduction O 0
or O 0
discontinuation O 0
, O 0
this O 0
approach O 0
compromises O 0
outcomes O 0
by O 0
significantly O 0
decreasing O 0
SVR O 0
rates O 0
. O 0

Recombinant O 0
human O 0
erythropoietin O 0
has O 0
been O 0
used O 0
to O 0
manage O 0
ribavirin B-Chemical 0
- O 0
associated O 0
anemia B-Disease 0
but O 0
has O 0
other O 0
potential O 0
disadvantages O 0
. O 0

Viramidine B-Chemical 0
, O 0
a O 0
liver O 0
- O 0
targeting O 0
prodrug O 0
of O 0
ribavirin B-Chemical 0
, O 0
has O 0
the O 0
potential O 0
to O 0
maintain O 0
the O 0
virologic O 0
efficacy O 0
of O 0
ribavirin B-Chemical 0
while O 0
decreasing O 0
the O 0
risk O 0
of O 0
hemolytic B-Disease 0
anemia I-Disease 0
in O 0
patients O 0
with O 0
chronic B-Disease 0
hepatitis I-Disease 0
C I-Disease 0
. O 0

Impact O 0
of O 0
alcohol B-Chemical 0
exposure O 0
after O 0
pregnancy O 0
recognition O 0
on O 0
ultrasonographic O 0
fetal O 0
growth O 0
measures O 0
. O 0

BACKGROUND O 0
: O 0
More O 0
than O 0
3 O 0
decades O 0
after O 0
Jones O 0
and O 0
Smith O 0
( O 0
1973 O 0
) O 0
reported O 0
on O 0
the O 0
devastation O 0
caused O 0
by O 0
alcohol B-Chemical 0
exposure O 0
on O 0
fetal O 0
development O 0
, O 0
the O 0
rates O 0
of O 0
heavy O 0
drinking O 0
during O 0
pregnancy O 0
remain O 0
relatively O 0
unchanged O 0
. O 0

Early O 0
identification O 0
of O 0
fetal O 0
alcohol B-Chemical 0
exposure O 0
and O 0
maternal O 0
abstinence O 0
led O 0
to O 0
better O 0
infant O 0
outcomes O 0
. O 0

This O 0
study O 0
examined O 0
the O 0
utility O 0
of O 0
biometry O 0
for O 0
detecting O 0
alcohol B-Chemical 0
- O 0
related O 0
fetal O 0
growth B-Disease 0
impairment I-Disease 0
. O 0

METHODS O 0
: O 0
We O 0
obtained O 0
fetal O 0
ultrasound O 0
measures O 0
from O 0
routine O 0
ultrasound O 0
examinations O 0
for O 0
167 O 0
pregnant O 0
hazardous O 0
drinkers O 0
who O 0
were O 0
enrolled O 0
in O 0
a O 0
brief O 0
alcohol B-Chemical 0
intervention O 0
study O 0
. O 0

The O 0
fetal O 0
measures O 0
for O 0
women O 0
who O 0
quit O 0
after O 0
learning O 0
of O 0
their O 0
pregnancies O 0
were O 0
compared O 0
with O 0
measures O 0
for O 0
women O 0
who O 0
continued O 0
some O 0
drinking O 0
throughout O 0
the O 0
course O 0
of O 0
their O 0
pregnancies O 0
. O 0

Because O 0
intensity O 0
of O 0
alcohol B-Chemical 0
consumption O 0
is O 0
associated O 0
with O 0
poorer O 0
fetal O 0
outcomes O 0
, O 0
separate O 0
analyses O 0
were O 0
conducted O 0
for O 0
the O 0
heavy O 0
( O 0
average O 0
of O 0
> O 0
or O 0
= O 0
5 O 0
drinks O 0
per O 0
drinking O 0
day O 0
) O 0
alcohol B-Chemical 0
consumers O 0
. O 0

Fetal O 0
measures O 0
from O 0
the O 0
heavy O 0
- O 0
exposed O 0
fetuses O 0
were O 0
also O 0
compared O 0
with O 0
measures O 0
from O 0
a O 0
nondrinking O 0
group O 0
that O 0
was O 0
representative O 0
of O 0
normal O 0
, O 0
uncomplicated O 0
pregnancies O 0
from O 0
our O 0
clinics O 0
. O 0

Analyses O 0
of O 0
covariance O 0
were O 0
used O 0
to O 0
determine O 0
whether O 0
there O 0
were O 0
differences O 0
between O 0
groups O 0
after O 0
controlling O 0
for O 0
influences O 0
of O 0
gestational O 0
age O 0
and O 0
drug B-Disease 0
abuse I-Disease 0
. O 0

RESULTS O 0
: O 0
Nearly O 0
half O 0
of O 0
the O 0
pregnant O 0
drinkers O 0
abstained O 0
after O 0
learning O 0
of O 0
their O 0
pregnancies O 0
. O 0

When O 0
women O 0
reportedly O 0
quit O 0
drinking O 0
early O 0
in O 0
their O 0
pregnancies O 0
, O 0
fetal O 0
growth O 0
measures O 0
were O 0
not O 0
significantly O 0
different O 0
from O 0
a O 0
non O 0
- O 0
alcohol B-Chemical 0
- O 0
exposed O 0
group O 0
, O 0
regardless O 0
of O 0
prior O 0
drinking O 0
patterns O 0
. O 0

Any O 0
alcohol B-Chemical 0
consumption O 0
postpregnancy O 0
recognition O 0
among O 0
the O 0
heavy O 0
drinkers O 0
resulted O 0
in O 0
reduced B-Disease 0
cerebellar I-Disease 0
growth I-Disease 0
as O 0
well O 0
as O 0
decreased B-Disease 0
cranial I-Disease 0
to I-Disease 0
body I-Disease 0
growth I-Disease 0
in O 0
comparison O 0
with O 0
women O 0
who O 0
either O 0
quit O 0
drinking O 0
or O 0
who O 0
were O 0
nondrinkers O 0
. O 0

Amphetamine B-Chemical 0
abuse O 0
was O 0
predictive O 0
of O 0
larger O 0
cranial O 0
to O 0
body O 0
growth O 0
ratios O 0
. O 0

CONCLUSIONS O 0
: O 0
Alterations O 0
in O 0
fetal O 0
biometric O 0
measurements O 0
were O 0
observed O 0
among O 0
the O 0
heavy O 0
drinkers O 0
only O 0
when O 0
they O 0
continued O 0
drinking O 0
after O 0
becoming O 0
aware O 0
of O 0
their O 0
pregnancies O 0
. O 0

Although O 0
the O 0
reliance O 0
on O 0
self O 0
- O 0
reported O 0
drinking O 0
is O 0
a O 0
limitation O 0
in O 0
this O 0
study O 0
, O 0
these O 0
findings O 0
support O 0
the O 0
benefits O 0
of O 0
early O 0
abstinence O 0
and O 0
the O 0
potential O 0
for O 0
ultrasound O 0
examinations O 0
in O 0
the O 0
detection O 0
of O 0
fetal O 0
alcohol B-Chemical 0
effects O 0
. O 0

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

INTRODUCTION O 0
: O 0
Ethambutol B-Chemical 0
is O 0
used O 0
in O 0
the O 0
treatment O 0
of O 0
tuberculosis B-Disease 0
, O 0
which O 0
is O 0
still O 0
prevalent O 0
in O 0
Southeast O 0
Asia O 0
, O 0
and O 0
can O 0
be O 0
associated O 0
with O 0
permanent O 0
visual B-Disease 0
loss I-Disease 0
. O 0

We O 0
report O 0
3 O 0
cases O 0
which O 0
presented O 0
with O 0
bitemporal B-Disease 0
hemianopia I-Disease 0
. O 0

CLINICAL O 0
PICTURE O 0
: O 0
Three O 0
patients O 0
with O 0
ethambutol B-Chemical 0
- O 0
associated O 0
toxic O 0
optic B-Disease 0
neuropathy I-Disease 0
are O 0
described O 0
. O 0

All O 0
3 O 0
patients O 0
had O 0
loss B-Disease 0
of I-Disease 0
central I-Disease 0
visual I-Disease 0
acuity I-Disease 0
, I-Disease 0
colour I-Disease 0
vision I-Disease 0
( I-Disease 0
Ishihara I-Disease 0
) I-Disease 0
and I-Disease 0
visual I-Disease 0
field I-Disease 0
. O 0

The O 0
visual B-Disease 0
field I-Disease 0
loss I-Disease 0
had O 0
a O 0
bitemporal O 0
flavour O 0
, O 0
suggesting O 0
involvement O 0
of O 0
the O 0
optic O 0
chiasm O 0
. O 0

TREATMENT O 0
: O 0
Despite O 0
stopping O 0
ethambutol B-Chemical 0
on O 0
diagnosis O 0
, O 0
visual O 0
function O 0
continued O 0
to O 0
deteriorate O 0
for O 0
a O 0
few O 0
months O 0
. O 0

Subsequent O 0
improvement O 0
was O 0
mild O 0
in O 0
2 O 0
cases O 0
. O 0

In O 0
the O 0
third O 0
case O 0
, O 0
visual O 0
acuity O 0
and O 0
colour O 0
vision O 0
normalised O 0
but O 0
the O 0
optic O 0
discs O 0
were O 0
pale O 0
. O 0

OUTCOME O 0
: O 0
All O 0
3 O 0
patients O 0
had O 0
some O 0
permanent O 0
loss B-Disease 0
of I-Disease 0
visual I-Disease 0
function I-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
Ethambutol B-Chemical 0
usage O 0
is O 0
associated O 0
with O 0
permanent O 0
visual B-Disease 0
loss I-Disease 0
and O 0
should O 0
be O 0
avoided O 0
if O 0
possible O 0
or O 0
used O 0
with O 0
caution O 0
and O 0
proper O 0
ophthalmological O 0
follow O 0
- O 0
up O 0
. O 0

The O 0
author O 0
postulates O 0
that O 0
in O 0
cases O 0
of O 0
ethambutol B-Chemical 0
associated O 0
chiasmopathy O 0
, O 0
ethambutol B-Chemical 0
may O 0
initially O 0
affect O 0
the O 0
optic O 0
nerves O 0
and O 0
subsequently O 0
progress O 0
to O 0
involve O 0
the O 0
optic O 0
chiasm O 0
. O 0

Possible O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
related O 0
to O 0
concomitant O 0
treatment O 0
with O 0
paroxetine B-Chemical 0
and O 0
alprazolam B-Chemical 0
. O 0

A O 0
74 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
depressive B-Disease 0
symptoms I-Disease 0
was O 0
admitted O 0
to O 0
a O 0
psychiatric B-Disease 0
hospital O 0
due O 0
to O 0
insomnia B-Disease 0
, O 0
loss B-Disease 0
of I-Disease 0
appetite I-Disease 0
, O 0
exhaustion O 0
, O 0
and O 0
agitation B-Disease 0
. O 0

Medical O 0
treatment O 0
was O 0
initiated O 0
at O 0
a O 0
daily O 0
dose O 0
of O 0
20 O 0
mg O 0
paroxetine B-Chemical 0
and O 0
1 O 0
. O 0
2 O 0
mg O 0
alprazolam B-Chemical 0
. O 0

On O 0
the O 0
10th O 0
day O 0
of O 0
paroxetine B-Chemical 0
and O 0
alprazolam B-Chemical 0
treatment O 0
, O 0
the O 0
patient O 0
exhibited O 0
marked O 0
psychomotor B-Disease 0
retardation I-Disease 0
, O 0
disorientation O 0
, O 0
and O 0
severe O 0
muscle B-Disease 0
rigidity I-Disease 0
with O 0
tremors B-Disease 0
. O 0

The O 0
patient O 0
had O 0
a O 0
fever B-Disease 0
( O 0
38 O 0
. O 0
2 O 0
degrees O 0
C O 0
) O 0
, O 0
fluctuating O 0
blood O 0
pressure O 0
( O 0
between O 0
165 O 0
/ O 0
90 O 0
and O 0
130 O 0
/ O 0
70 O 0
mg O 0
mm O 0
Hg O 0
) O 0
, O 0
and O 0
severe O 0
extrapyramidal B-Disease 0
symptoms I-Disease 0
. O 0

Laboratory O 0
tests O 0
showed O 0
an O 0
elevation O 0
of O 0
creatine B-Chemical 0
phosphokinase O 0
( O 0
2218 O 0
IU O 0
/ O 0
L O 0
) O 0
, O 0
aspartate B-Chemical 0
aminotransferase O 0
( O 0
134 O 0
IU O 0
/ O 0
L O 0
) O 0
, O 0
alanine B-Chemical 0
aminotransferase O 0
( O 0
78 O 0
IU O 0
/ O 0
L O 0
) O 0
, O 0
and O 0
BUN O 0
( O 0
27 O 0
. O 0
9 O 0
mg O 0
/ O 0
ml O 0
) O 0
levels O 0
. O 0

The O 0
patient O 0
received O 0
bromocriptine B-Chemical 0
and O 0
diazepam B-Chemical 0
to O 0
treat O 0
his O 0
symptoms O 0
. O 0

7 O 0
days O 0
later O 0
, O 0
the O 0
fever B-Disease 0
disappeared O 0
and O 0
the O 0
patient O 0
' O 0
s O 0
serum O 0
CPK O 0
levels O 0
were O 0
normalized O 0
( O 0
175 O 0
IU O 0
/ O 0
L O 0
) O 0
. O 0

This O 0
patient O 0
presented O 0
with O 0
symptoms O 0
of O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
( O 0
NMS B-Disease 0
) O 0
, O 0
thus O 0
demonstrating O 0
that O 0
NMS B-Disease 0
- O 0
like O 0
symptoms O 0
can O 0
occur O 0
after O 0
combined O 0
paroxetine B-Chemical 0
and O 0
alprazolam B-Chemical 0
treatment O 0
. O 0

The O 0
adverse O 0
drug O 0
reaction O 0
score O 0
obtained O 0
by O 0
the O 0
Naranjo O 0
algorithm O 0
was O 0
6 O 0
in O 0
our O 0
case O 0
, O 0
indicating 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
NMS B-Disease 0
- O 0
like O 0
adverse O 0
symptoms O 0
and O 0
the O 0
combined O 0
treatment O 0
used O 0
in O 0
this O 0
case O 0
. O 0

The O 0
involvement O 0
of O 0
physiologic O 0
and O 0
environmental O 0
aspects O 0
specific O 0
to O 0
this O 0
patient O 0
was O 0
suspected O 0
. O 0

Several O 0
risk O 0
factors O 0
for O 0
NMS B-Disease 0
should O 0
be O 0
noted O 0
in O 0
elderly O 0
depressive B-Disease 0
patients O 0
whose O 0
symptoms O 0
often O 0
include O 0
dehydration B-Disease 0
, O 0
agitation B-Disease 0
, O 0
malnutrition B-Disease 0
, O 0
and O 0
exhaustion O 0
. O 0

Careful O 0
therapeutic O 0
intervention O 0
is O 0
necessary O 0
in O 0
cases O 0
involving O 0
elderly O 0
patients O 0
who O 0
suffer O 0
from O 0
depression B-Disease 0
. O 0

Down O 0
- O 0
regulation O 0
of O 0
norepinephrine B-Chemical 0
transporter O 0
function O 0
induced O 0
by O 0
chronic O 0
administration O 0
of O 0
desipramine B-Chemical 0
linking O 0
to O 0
the O 0
alteration O 0
of O 0
sensitivity O 0
of O 0
local O 0
- O 0
anesthetics O 0
- O 0
induced O 0
convulsions B-Disease 0
and O 0
the O 0
counteraction O 0
by O 0
co O 0
- O 0
administration O 0
with O 0
local O 0
anesthetics O 0
. O 0

Alterations O 0
of O 0
norepinephrine B-Chemical 0
transporter O 0
( O 0
NET O 0
) O 0
function O 0
by O 0
chronic O 0
inhibition O 0
of O 0
NET O 0
in O 0
relation O 0
to O 0
sensitization O 0
to O 0
seizures B-Disease 0
induce O 0
by O 0
cocaine B-Chemical 0
and O 0
local O 0
anesthetics O 0
were O 0
studied O 0
in O 0
mice O 0
. O 0

Daily O 0
administration O 0
of O 0
desipramine B-Chemical 0
, O 0
an O 0
inhibitor O 0
of O 0
the O 0
NET O 0
, O 0
for O 0
5 O 0
days O 0
decreased O 0
[ O 0
( O 0
3 O 0
) O 0
H O 0
] O 0
norepinephrine B-Chemical 0
uptake O 0
in O 0
the O 0
P2 O 0
fractions O 0
of O 0
hippocampus O 0
but O 0
not O 0
cortex O 0
, O 0
striatum O 0
or O 0
amygdalae O 0
. O 0

Co O 0
- O 0
administration O 0
of O 0
lidocaine B-Chemical 0
, O 0
bupivacaine B-Chemical 0
or O 0
tricaine B-Chemical 0
with O 0
desipramine B-Chemical 0
reversed O 0
this O 0
effect O 0
. O 0

Daily O 0
treatment O 0
of O 0
cocaine B-Chemical 0
increased O 0
[ O 0
( O 0
3 O 0
) O 0
H O 0
] O 0
norepinephrine B-Chemical 0
uptake O 0
into O 0
the O 0
hippocampus O 0
. O 0

Daily O 0
administration O 0
of O 0
desipramine B-Chemical 0
increased O 0
the O 0
incidence O 0
of O 0
appearance O 0
of O 0
lidocaine B-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
and O 0
decreased O 0
that O 0
of O 0
cocaine B-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
. O 0

Co O 0
- O 0
administration O 0
of O 0
lidocaine B-Chemical 0
with O 0
desipramine B-Chemical 0
reversed O 0
the O 0
changes O 0
of O 0
convulsive B-Disease 0
activity O 0
of O 0
lidocaine B-Chemical 0
and O 0
cocaine B-Chemical 0
induced O 0
by O 0
repeated O 0
administration O 0
of O 0
desipramine B-Chemical 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
down O 0
- O 0
regulation O 0
of O 0
hippocampal O 0
NET O 0
induced O 0
by O 0
chronic O 0
administration O 0
of O 0
desipramine B-Chemical 0
may O 0
be O 0
relevant O 0
to O 0
desipramine B-Chemical 0
- O 0
induced O 0
sensitization O 0
of O 0
lidocaine B-Chemical 0
convulsions B-Disease 0
. O 0

Inhibition O 0
of O 0
Na B-Chemical 0
( O 0
+ O 0
) O 0
channels O 0
by O 0
local O 0
anesthetics O 0
may O 0
regulate O 0
desipramine B-Chemical 0
- O 0
induced O 0
down O 0
- O 0
regulation O 0
of O 0
NET O 0
function O 0
. O 0

Repeated O 0
administration O 0
of O 0
cocaine B-Chemical 0
induces O 0
up O 0
- O 0
regulation O 0
of O 0
hippocampal O 0
NET O 0
function O 0
. O 0

Desipramine B-Chemical 0
- O 0
induced O 0
sensitization O 0
of O 0
lidocaine B-Chemical 0
seizures B-Disease 0
may O 0
have O 0
a O 0
mechanism O 0
distinct O 0
from O 0
kindling O 0
resulting O 0
from O 0
repeated O 0
administration O 0
of O 0
cocaine B-Chemical 0
. O 0

Atorvastatin B-Chemical 0
prevented O 0
and O 0
reversed O 0
dexamethasone B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
in O 0
the O 0
rat O 0
. O 0

To O 0
assess O 0
the O 0
antioxidant O 0
effects O 0
of O 0
atorvastatin B-Chemical 0
( O 0
atorva B-Chemical 0
) O 0
on O 0
dexamethasone B-Chemical 0
( O 0
dex B-Chemical 0
) O 0
- O 0
induced O 0
hypertension B-Disease 0
, O 0
60 O 0
male O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
were O 0
treated O 0
with O 0
atorva B-Chemical 0
30 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
or O 0
tap O 0
water O 0
for O 0
15 O 0
days O 0
. O 0

Dex B-Chemical 0
increased O 0
systolic O 0
blood O 0
pressure O 0
( O 0
SBP O 0
) O 0
from O 0
109 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
8 O 0
to O 0
135 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
6 O 0
mmHg O 0
and O 0
plasma O 0
superoxide B-Chemical 0
( O 0
5711 O 0
+ O 0
/ O 0
- O 0
284 O 0
. O 0
9 O 0
saline O 0
, O 0
7931 O 0
+ O 0
/ O 0
- O 0
392 O 0
. O 0
8 O 0
U O 0
/ O 0
ml O 0
dex B-Chemical 0
, O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

In O 0
this O 0
prevention O 0
study O 0
, O 0
SBP O 0
in O 0
the O 0
atorva B-Chemical 0
+ O 0
dex B-Chemical 0
group O 0
was O 0
increased O 0
from O 0
115 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
4 O 0
to O 0
124 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
5 O 0
mmHg O 0
, O 0
but O 0
this O 0
was O 0
significantly O 0
lower O 0
than O 0
in O 0
the O 0
dex B-Chemical 0
- O 0
only O 0
group O 0
( O 0
P O 0
' O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Atorva B-Chemical 0
reversed O 0
dex B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
( O 0
129 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
6 O 0
mmHg O 0
, O 0
vs O 0
. O 0
135 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
6 O 0
mmHg O 0
P O 0
' O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
and O 0
decreased O 0
plasma O 0
superoxide B-Chemical 0
( O 0
7931 O 0
+ O 0
/ O 0
- O 0
392 O 0
. O 0
8 O 0
dex B-Chemical 0
, O 0
1187 O 0
+ O 0
/ O 0
- O 0
441 O 0
. O 0
2 O 0
atorva B-Chemical 0
+ O 0
dex B-Chemical 0
, O 0
P O 0
< O 0
0 O 0
. O 0
0001 O 0
) O 0
. O 0

Plasma O 0
nitrate B-Chemical 0
/ O 0
nitrite B-Chemical 0
( O 0
NOx O 0
) O 0
was O 0
decreased O 0
in O 0
dex B-Chemical 0
- O 0
treated O 0
rats O 0
compared O 0
to O 0
saline O 0
- O 0
treated O 0
rats O 0
( O 0
11 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
08 O 0
microm O 0
, O 0
15 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
17 O 0
microm O 0
, O 0
respectively O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Atorva B-Chemical 0
affected O 0
neither O 0
plasma O 0
NOx O 0
nor O 0
thymus O 0
weight O 0
. O 0

Thus O 0
, O 0
atorvastatin B-Chemical 0
prevented O 0
and O 0
reversed O 0
dexamethasone B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
in O 0
the O 0
rat O 0
. O 0

Peripheral B-Disease 0
neuropathy I-Disease 0
caused O 0
by O 0
high O 0
- O 0
dose O 0
cytosine B-Chemical 0
arabinoside I-Chemical 0
treatment O 0
in O 0
a O 0
patient O 0
with O 0
acute B-Disease 0
myeloid I-Disease 0
leukemia I-Disease 0
. O 0

The O 0
central O 0
nervous O 0
system O 0
toxicity B-Disease 0
of O 0
high O 0
- O 0
dose O 0
cytosine B-Chemical 0
arabinoside I-Chemical 0
is O 0
well O 0
recognized O 0
, O 0
but O 0
the O 0
toxicity B-Disease 0
of O 0
cytosine B-Chemical 0
arabinoside I-Chemical 0
in O 0
the O 0
peripheral O 0
nervous O 0
system O 0
has O 0
been O 0
infrequently O 0
reported O 0
. O 0

A O 0
49 O 0
- O 0
year O 0
- O 0
old O 0
Japanese O 0
man O 0
was O 0
diagnosed O 0
with O 0
acute B-Disease 0
myeloid I-Disease 0
leukemia I-Disease 0
. O 0

After O 0
he O 0
achieved O 0
complete O 0
remission O 0
, O 0
he O 0
received O 0
high O 0
- O 0
dose O 0
cytosine B-Chemical 0
arabinoside I-Chemical 0
treatment O 0
( O 0
2 O 0
g O 0
/ O 0
m2 O 0
twice O 0
a O 0
day O 0
for O 0
5 O 0
days O 0
; O 0
total O 0
, O 0
20 O 0
g O 0
/ O 0
m2 O 0
) O 0
as O 0
consolidation O 0
therapy O 0
. O 0

The O 0
first O 0
course O 0
of O 0
high O 0
- O 0
dose O 0
cytosine B-Chemical 0
arabinoside I-Chemical 0
resulted O 0
in O 0
no O 0
unusual O 0
symptoms O 0
, O 0
but O 0
on O 0
day O 0
21 O 0
of O 0
the O 0
second O 0
course O 0
of O 0
treatment O 0
, O 0
the O 0
patient O 0
complained O 0
of O 0
numbness B-Disease 0
in O 0
his O 0
right O 0
foot O 0
. O 0

Electromyogram O 0
and O 0
nerve O 0
- O 0
conduction O 0
studies O 0
showed O 0
peripheral B-Disease 0
neuropathy I-Disease 0
in O 0
both O 0
peroneal O 0
nerves O 0
. O 0

This O 0
neuropathy B-Disease 0
was O 0
gradually O 0
resolving O 0
; O 0
however O 0
, O 0
after O 0
the O 0
patient O 0
received O 0
allogeneic O 0
bone O 0
marrow O 0
transplantation O 0
, O 0
the O 0
symptoms O 0
worsened O 0
, O 0
with O 0
the O 0
development O 0
of O 0
graft B-Disease 0
- I-Disease 0
versus I-Disease 0
- I-Disease 0
host I-Disease 0
disease I-Disease 0
, O 0
and O 0
the O 0
symptoms O 0
subsequently O 0
responded O 0
to O 0
methylprednisolone B-Chemical 0
. O 0

Although O 0
the O 0
mechanisms O 0
of O 0
peripheral B-Disease 0
neuropathy I-Disease 0
are O 0
still O 0
unclear O 0
, O 0
high O 0
- O 0
dose O 0
cytosine B-Chemical 0
arabinoside I-Chemical 0
is O 0
a O 0
therapy O 0
that O 0
is O 0
potentially O 0
toxic O 0
to O 0
the O 0
peripheral O 0
nervous O 0
system O 0
, O 0
and O 0
auto O 0
/ O 0
alloimmunity O 0
may O 0
play O 0
an O 0
important O 0
role O 0
in O 0
these O 0
mechanisms O 0
. O 0

Effect O 0
of O 0
alpha B-Chemical 0
- I-Chemical 0
tocopherol I-Chemical 0
and O 0
deferoxamine B-Chemical 0
on O 0
methamphetamine B-Chemical 0
- O 0
induced O 0
neurotoxicity B-Disease 0
. O 0

Methamphetamine B-Chemical 0
( O 0
MA B-Chemical 0
) O 0
- O 0
induced O 0
dopaminergic O 0
neurotoxicity B-Disease 0
is O 0
believed O 0
to O 0
be O 0
associated O 0
with O 0
the O 0
increased O 0
formation O 0
of O 0
free O 0
radicals O 0
. O 0

This O 0
study O 0
examined O 0
the O 0
effect O 0
of O 0
alpha B-Chemical 0
- I-Chemical 0
tocopherol I-Chemical 0
( O 0
alpha B-Chemical 0
- I-Chemical 0
TC I-Chemical 0
) O 0
, O 0
a O 0
scavenger O 0
of O 0
reactive O 0
oxygen B-Chemical 0
species O 0
, O 0
and O 0
deferoxamine B-Chemical 0
( O 0
DFO B-Chemical 0
) O 0
, O 0
an O 0
iron B-Chemical 0
chelator O 0
, O 0
on O 0
the O 0
MA B-Chemical 0
- O 0
induced O 0
neurotoxicity B-Disease 0
. O 0

Male O 0
rats O 0
were O 0
treated O 0
with O 0
MA B-Chemical 0
( O 0
10 O 0
mg O 0
/ O 0
kg O 0
, O 0
every O 0
2 O 0
h O 0
for O 0
four O 0
injections O 0
) O 0
. O 0

The O 0
rat O 0
received O 0
either O 0
alpha B-Chemical 0
- I-Chemical 0
TC I-Chemical 0
( O 0
20 O 0
mg O 0
/ O 0
kg O 0
) O 0
intraperitoneally O 0
for O 0
3 O 0
days O 0
and O 0
30 O 0
min O 0
prior O 0
to O 0
MA B-Chemical 0
administration O 0
or O 0
DFO B-Chemical 0
( O 0
50 O 0
mg O 0
/ O 0
kg O 0
) O 0
subcutaneously O 0
30 O 0
min O 0
before O 0
MA B-Chemical 0
administration O 0
. O 0

The O 0
concentrations O 0
of O 0
dopamine B-Chemical 0
( O 0
DA B-Chemical 0
) O 0
, O 0
serotonin B-Chemical 0
and O 0
their O 0
metabolites O 0
decreased O 0
significantly O 0
after O 0
MA B-Chemical 0
administration O 0
, O 0
which O 0
was O 0
inhibited O 0
by O 0
the O 0
alpha B-Chemical 0
- I-Chemical 0
TC I-Chemical 0
and O 0
DFO B-Chemical 0
pretreatment O 0
. O 0

alpha B-Chemical 0
- I-Chemical 0
TC I-Chemical 0
and O 0
DFO B-Chemical 0
attenuated O 0
the O 0
MA B-Chemical 0
- O 0
induced O 0
hyperthermia B-Disease 0
as O 0
well O 0
as O 0
the O 0
alterations O 0
in O 0
the O 0
locomotor O 0
activity O 0
. O 0

The O 0
level O 0
of O 0
lipid O 0
peroxidation O 0
was O 0
higher O 0
and O 0
the O 0
reduced O 0
glutathione B-Chemical 0
concentration O 0
was O 0
lower O 0
in O 0
the O 0
MA B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

These O 0
changes O 0
were O 0
significantly O 0
attenuated O 0
by O 0
alpha B-Chemical 0
- I-Chemical 0
TC I-Chemical 0
and O 0
DFO B-Chemical 0
. O 0

This O 0
suggests O 0
that O 0
alpha B-Chemical 0
- I-Chemical 0
TC I-Chemical 0
and O 0
DFO B-Chemical 0
ameliorate O 0
the O 0
MA B-Chemical 0
- O 0
induced O 0
neuronal B-Disease 0
damage I-Disease 0
by O 0
decreasing O 0
the O 0
level O 0
of O 0
oxidative O 0
stress O 0
. O 0

Blockade O 0
of O 0
both O 0
D O 0
- O 0
1 O 0
and O 0
D O 0
- O 0
2 O 0
dopamine B-Chemical 0
receptors O 0
may O 0
induce O 0
catalepsy B-Disease 0
in O 0
mice O 0
. O 0

1 O 0
. O 0

The O 0
catalepsy B-Disease 0
induced O 0
by O 0
dopamine B-Chemical 0
antagonists O 0
has O 0
been O 0
tested O 0
and O 0
the O 0
possible O 0
dopamine B-Chemical 0
subtypes O 0
involved O 0
in O 0
catalepsy B-Disease 0
was O 0
determined O 0
. O 0

2 O 0
. O 0

Dopamine B-Chemical 0
antagonist O 0
fluphenazine B-Chemical 0
, O 0
D O 0
- O 0
1 O 0
antagonist O 0
SCH B-Chemical 0
23390 I-Chemical 0
or O 0
D O 0
- O 0
2 O 0
antagonist O 0
sulpiride B-Chemical 0
induced O 0
catalepsy B-Disease 0
. O 0

The O 0
effect O 0
of O 0
fluphenazine B-Chemical 0
and O 0
sulpiride B-Chemical 0
was O 0
dose O 0
- O 0
dependent O 0
. O 0

Combination O 0
of O 0
SCH B-Chemical 0
23390 I-Chemical 0
with O 0
sulpiride B-Chemical 0
did O 0
not O 0
induce O 0
catalepsy B-Disease 0
potentiation O 0
. O 0

3 O 0
. O 0

D O 0
- O 0
1 O 0
agonist O 0
SKF B-Chemical 0
38393 I-Chemical 0
or O 0
D O 0
- O 0
2 O 0
agonist O 0
quinpirole B-Chemical 0
decreased O 0
the O 0
catalepsy B-Disease 0
induced O 0
by O 0
fluphenazine B-Chemical 0
, O 0
SCH B-Chemical 0
23390 I-Chemical 0
or O 0
sulpiride B-Chemical 0
. O 0

4 O 0
. O 0

Combination O 0
of O 0
SKF B-Chemical 0
38393 I-Chemical 0
with O 0
quinpirole B-Chemical 0
did O 0
not O 0
cause O 0
potentiated O 0
inhibitory O 0
effect O 0
on O 0
catalepsy B-Disease 0
induced O 0
by O 0
dopamine B-Chemical 0
antagonists O 0
. O 0

5 O 0
. O 0

The O 0
data O 0
may O 0
indicate O 0
that O 0
although O 0
D O 0
- O 0
2 O 0
receptor O 0
blockade O 0
is O 0
involved O 0
in O 0
catalepsy B-Disease 0
, O 0
the O 0
D O 0
- O 0
1 O 0
receptor O 0
may O 0
plan O 0
a O 0
role O 0
. O 0

Sustained O 0
clinical O 0
improvement O 0
of O 0
a O 0
patient O 0
with O 0
decompensated O 0
hepatitis B-Disease 0
B I-Disease 0
virus O 0
- O 0
related O 0
cirrhosis B-Disease 0
after O 0
treatment O 0
with O 0
lamivudine B-Chemical 0
monotherapy O 0
. O 0

Hepatitis B-Disease 0
B I-Disease 0
virus I-Disease 0
( I-Disease 0
HBV I-Disease 0
) I-Disease 0
infection I-Disease 0
, O 0
which O 0
causes O 0
liver B-Disease 0
cirrhosis I-Disease 0
and O 0
hepatocellular B-Disease 0
carcinoma I-Disease 0
, O 0
remains O 0
a O 0
major O 0
health O 0
problem O 0
in O 0
Asian O 0
countries O 0
. O 0

Recent O 0
development O 0
of O 0
vaccine O 0
for O 0
prevention O 0
is O 0
reported O 0
to O 0
be O 0
successful O 0
in O 0
reducing O 0
the O 0
size O 0
of O 0
chronically O 0
infected O 0
carriers O 0
, O 0
although O 0
the O 0
standard O 0
medical O 0
therapies O 0
have O 0
not O 0
been O 0
established O 0
up O 0
to O 0
now O 0
. O 0

In O 0
this O 0
report O 0
, O 0
we O 0
encountered O 0
a O 0
patient O 0
with O 0
decompensated O 0
HBV O 0
- O 0
related O 0
cirrhosis B-Disease 0
who O 0
exhibited O 0
the O 0
dramatic O 0
improvements O 0
after O 0
antiviral O 0
therapy O 0
. O 0

The O 0
patient O 0
was O 0
a O 0
50 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
. O 0

Previous O 0
conventional O 0
medical O 0
treatments O 0
were O 0
not O 0
effective O 0
for O 0
this O 0
patient O 0
, O 0
thus O 0
this O 0
patient O 0
had O 0
been O 0
referred O 0
to O 0
our O 0
hospital O 0
. O 0

However O 0
, O 0
the O 0
administration O 0
of O 0
lamivudine B-Chemical 0
, O 0
a O 0
reverse O 0
transcriptase O 0
inhibitor O 0
, O 0
for O 0
23 O 0
months O 0
dramatically O 0
improved O 0
her O 0
liver O 0
severity O 0
. O 0

During O 0
this O 0
period O 0
, O 0
no O 0
drug O 0
resistant O 0
mutant O 0
HBV O 0
emerged O 0
, O 0
and O 0
the O 0
serum O 0
HBV O 0
- O 0
DNA O 0
level O 0
was O 0
continuously O 0
suppressed O 0
. O 0

These O 0
virological O 0
responses O 0
were O 0
also O 0
maintained O 0
even O 0
after O 0
the O 0
antiviral O 0
therapy O 0
was O 0
discontinued O 0
. O 0

Moreover O 0
, O 0
both O 0
hepatitis B-Chemical 0
B I-Chemical 0
surface I-Chemical 0
antigen I-Chemical 0
and I-Chemical 0
e I-Chemical 0
antigen I-Chemical 0
were O 0
observed O 0
to O 0
have O 0
disappeared O 0
in O 0
this O 0
patient O 0
. O 0

The O 0
administration O 0
of O 0
lamivudine B-Chemical 0
to O 0
patients O 0
with O 0
HBV O 0
- O 0
related O 0
cirrhosis B-Disease 0
, O 0
like O 0
our O 0
present O 0
case O 0
, O 0
should O 0
be O 0
considered O 0
as O 0
an O 0
initial O 0
medical O 0
therapeutic O 0
option O 0
, O 0
especially O 0
in O 0
countries O 0
where O 0
liver O 0
transplantation O 0
is O 0
not O 0
reliably O 0
available O 0
. O 0

Antiarrhythmic O 0
effects O 0
of O 0
optical O 0
isomers O 0
of O 0
cibenzoline B-Chemical 0
on O 0
canine O 0
ventricular B-Disease 0
arrhythmias I-Disease 0
. O 0

Antiarrhythmic O 0
effects O 0
of O 0
( O 0
+ O 0
) O 0
- O 0
cibenzoline B-Chemical 0
and O 0
( O 0
- O 0
) O 0
- O 0
cibenzoline B-Chemical 0
were O 0
examined O 0
using O 0
two O 0
canine O 0
ventricular B-Disease 0
arrhythmia I-Disease 0
models O 0
. O 0

Digitalis B-Chemical 0
arrhythmia B-Disease 0
, O 0
which O 0
is O 0
suppressed O 0
by O 0
Na B-Chemical 0
channel O 0
blockers O 0
, O 0
was O 0
induced O 0
by O 0
intermittent 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
ouabain B-Chemical 0
in O 0
pentobarbital B-Chemical 0
- O 0
anesthetized O 0
dogs O 0
. O 0

Adrenaline B-Disease 0
arrhythmia I-Disease 0
, O 0
which O 0
is O 0
suppressed O 0
by O 0
Ca B-Chemical 0
channel O 0
blockers O 0
, O 0
was O 0
induced O 0
by O 0
adrenaline B-Chemical 0
infusion O 0
in O 0
halothane B-Chemical 0
- O 0
anesthetized O 0
dogs O 0
. O 0

Ten O 0
and 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
+ O 0
) O 0
- O 0
cibenzoline B-Chemical 0
suppressed O 0
digitalis B-Chemical 0
- O 0
and O 0
adrenaline B-Chemical 0
- O 0
induced O 0
arrhythmias B-Disease 0
, O 0
respectively O 0
. O 0

The O 0
minimum O 0
effective O 0
plasma O 0
concentrations O 0
of O 0
( O 0
+ O 0
) O 0
- O 0
cibenzoline B-Chemical 0
for O 0
digitalis B-Chemical 0
- O 0
and O 0
adrenaline B-Chemical 0
- O 0
induced O 0
arrhythmias B-Disease 0
were O 0
1 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
4 O 0
and O 0
2 O 0
. O 0
0 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
6 O 0
micrograms O 0
/ O 0
ml O 0
, O 0
respectively O 0
( O 0
mean O 0
+ O 0
/ O 0
- O 0
SD O 0
, O 0
n O 0
= O 0
6 O 0
) O 0
. O 0

A O 0
lower O 0
dose O 0
of O 0
1 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
of O 0
( O 0
- O 0
) O 0
- O 0
cibenzoline B-Chemical 0
suppressed O 0
the O 0
digitalis B-Chemical 0
- O 0
induced O 0
arrhythmia B-Disease 0
, O 0
whereas O 0
5 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
was O 0
needed O 0
to O 0
suppress O 0
adrenaline B-Chemical 0
- O 0
induced O 0
arrhythmias B-Disease 0
. O 0

The O 0
minimum O 0
effective O 0
plasma O 0
concentrations O 0
of O 0
( O 0
- O 0
) O 0
- O 0
cibenzoline B-Chemical 0
for O 0
digitalis B-Chemical 0
- O 0
and O 0
adrenaline B-Chemical 0
- O 0
induced O 0
arrhythmia B-Disease 0
were O 0
0 O 0
. O 0
06 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
04 O 0
and O 0
0 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
micrograms O 0
/ O 0
ml O 0
, O 0
respectively O 0
( O 0
mean O 0
+ O 0
/ O 0
- O 0
SD O 0
, O 0
n O 0
= O 0
6 O 0
) O 0
. O 0

The O 0
stronger O 0
antiarrhythmic O 0
effect O 0
of O 0
( O 0
- O 0
) O 0
- O 0
cibenzoline B-Chemical 0
indicates O 0
that O 0
( O 0
- O 0
) O 0
- O 0
isomer O 0
may O 0
have O 0
an O 0
effect O 0
nearly O 0
5 O 0
- O 0
20 O 0
times O 0
stronger O 0
in O 0
suppressing O 0
Na B-Chemical 0
channels O 0
, O 0
but O 0
effects O 0
of O 0
both O 0
drugs O 0
on O 0
Ca B-Chemical 0
channels O 0
may O 0
be O 0
almost O 0
equipotent O 0
. O 0

Passage O 0
of O 0
mannitol B-Chemical 0
into O 0
the O 0
brain O 0
around O 0
gliomas B-Disease 0
: O 0
a O 0
potential O 0
cause O 0
of O 0
rebound O 0
phenomenon O 0
. O 0

A O 0
study O 0
on O 0
21 O 0
patients O 0
. O 0

AIM O 0
: O 0
Widespread O 0
use O 0
of O 0
mannitol B-Chemical 0
to O 0
reduce O 0
brain B-Disease 0
edema I-Disease 0
and O 0
lower O 0
elevated B-Disease 0
ICP I-Disease 0
in O 0
brain B-Disease 0
tumor I-Disease 0
patients O 0
continues O 0
to O 0
be O 0
afflicted O 0
by O 0
the O 0
so O 0
- O 0
called O 0
rebound O 0
phenomenon O 0
. O 0

Leakage O 0
of O 0
mannitol B-Chemical 0
into O 0
the O 0
brain O 0
parenchyma O 0
through O 0
an O 0
altered O 0
BBB O 0
and O 0
secondary O 0
reversal O 0
of O 0
osmotic O 0
gradient O 0
is O 0
considered O 0
the O 0
major O 0
cause O 0
of O 0
rebound O 0
. O 0

This O 0
has O 0
only O 0
been O 0
demonstrated O 0
experimentally O 0
in O 0
animals O 0
. O 0

As O 0
a O 0
contribution O 0
to O 0
this O 0
issue O 0
we O 0
decided O 0
to O 0
research O 0
the O 0
possible O 0
passage O 0
of O 0
mannitol B-Chemical 0
into O 0
the O 0
brain O 0
after O 0
administration O 0
to O 0
21 O 0
brain B-Disease 0
tumor I-Disease 0
patients O 0
. O 0

METHODS O 0
: O 0
Mannitol B-Chemical 0
( O 0
18 O 0
% O 0
solution O 0
; O 0
1 O 0
g O 0
/ O 0
kg O 0
) O 0
was O 0
administered O 0
as O 0
a O 0
bolus O 0
to O 0
patients O 0
( O 0
ten O 0
had O 0
malignant B-Disease 0
glioma I-Disease 0
, O 0
seven O 0
brain O 0
metastases B-Disease 0
and O 0
four O 0
meningioma B-Disease 0
) O 0
about O 0
30 O 0
minutes O 0
before O 0
craniotomy O 0
. O 0

During O 0
resection O 0
, O 0
a O 0
sample O 0
of O 0
the O 0
surrounding O 0
edematous B-Disease 0
white O 0
matter O 0
was O 0
taken O 0
at O 0
the O 0
same O 0
time O 0
as O 0
a O 0
10 O 0
ml O 0
venous O 0
blood O 0
sample O 0
. O 0

Mannitol B-Chemical 0
concentrations O 0
were O 0
measured O 0
in O 0
plasma O 0
and O 0
white O 0
matter O 0
by O 0
a O 0
modified O 0
version O 0
of O 0
the O 0
enzyme O 0
assay O 0
of O 0
Blonquist O 0
et O 0
al O 0
. O 0

RESULTS O 0
: O 0
In O 0
most O 0
glioma B-Disease 0
patients O 0
, O 0
mannitol B-Chemical 0
concentrations O 0
in O 0
white O 0
matter O 0
were O 0
2 O 0
to O 0
6 O 0
times O 0
higher O 0
than O 0
in O 0
plasma O 0
( O 0
mean O 0
3 O 0
. O 0
5 O 0
times O 0
) O 0
. O 0

In O 0
meningioma B-Disease 0
and O 0
metastases B-Disease 0
patients O 0
plasma O 0
concentrations O 0
of O 0
mannitol B-Chemical 0
were O 0
higher O 0
than O 0
white O 0
matter O 0
concentrations O 0
except O 0
in O 0
three O 0
cases O 0
with O 0
infiltration O 0
by O 0
neoplastic O 0
cells O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
results O 0
of O 0
our O 0
study O 0
show O 0
that O 0
even O 0
after O 0
a O 0
single O 0
bolus O 0
, O 0
mannitol B-Chemical 0
may O 0
leak O 0
through O 0
the O 0
altered O 0
BBB O 0
near O 0
gliomas B-Disease 0
, O 0
reversing O 0
the O 0
initial O 0
plasma O 0
- O 0
to O 0
- O 0
blood O 0
osmotic O 0
gradient O 0
, O 0
aggravating O 0
peritumoral O 0
edema B-Disease 0
and O 0
promoting O 0
rebound O 0
of O 0
ICP O 0
. O 0

Placebo O 0
- O 0
level O 0
incidence O 0
of O 0
extrapyramidal B-Disease 0
symptoms I-Disease 0
( O 0
EPS B-Disease 0
) O 0
with O 0
quetiapine B-Chemical 0
in O 0
controlled O 0
studies O 0
of O 0
patients O 0
with O 0
bipolar B-Disease 0
mania I-Disease 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
evaluate O 0
extrapyramidal B-Disease 0
symptoms I-Disease 0
( O 0
EPS B-Disease 0
) O 0
, O 0
including O 0
akathisia B-Disease 0
, O 0
with O 0
quetiapine B-Chemical 0
in O 0
patients O 0
with O 0
bipolar B-Disease 0
mania I-Disease 0
. O 0

METHODS O 0
: O 0
Data O 0
were O 0
analyzed O 0
from O 0
four O 0
similarly O 0
designed O 0
, O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
3 O 0
- O 0
to O 0
12 O 0
- O 0
week O 0
studies O 0
. O 0

Two O 0
studies O 0
evaluated O 0
quetiapine B-Chemical 0
monotherapy O 0
( O 0
up O 0
to O 0
800 O 0
mg O 0
/ O 0
day O 0
) O 0
( O 0
n O 0
= O 0
209 O 0
) O 0
versus O 0
placebo O 0
( O 0
n O 0
= O 0
198 O 0
) O 0
, O 0
with O 0
lithium B-Chemical 0
or O 0
haloperidol B-Chemical 0
monotherapy O 0
as O 0
respective O 0
active O 0
controls O 0
. O 0

Two O 0
studies O 0
evaluated O 0
quetiapine B-Chemical 0
( O 0
up O 0
to O 0
800 O 0
mg O 0
/ O 0
day O 0
) O 0
in O 0
combination O 0
with O 0
a O 0
mood O 0
stabilizer O 0
( O 0
lithium B-Chemical 0
or O 0
divalproex B-Chemical 0
, O 0
QTP B-Chemical 0
+ O 0
Li B-Chemical 0
/ O 0
DVP B-Chemical 0
) O 0
( O 0
n O 0
= O 0
196 O 0
) O 0
compared O 0
to O 0
placebo O 0
and O 0
mood O 0
stabilizer O 0
( O 0
PBO O 0
+ O 0
Li B-Chemical 0
/ O 0
DVP B-Chemical 0
) O 0
( O 0
n O 0
= O 0
203 O 0
) O 0
. O 0

Extrapyramidal B-Disease 0
symptoms I-Disease 0
were O 0
evaluated O 0
using O 0
the O 0
Simpson O 0
- O 0
Angus O 0
Scale O 0
( O 0
SAS O 0
) O 0
, O 0
the O 0
Barnes O 0
Akathisia O 0
Rating O 0
Scale O 0
( O 0
BARS O 0
) O 0
, O 0
adverse O 0
event O 0
reports O 0
and O 0
anticholinergic O 0
drug O 0
usage O 0
. O 0

RESULTS O 0
: O 0
The O 0
incidence O 0
of O 0
EPS B-Disease 0
- O 0
related O 0
adverse O 0
events O 0
, O 0
including O 0
akathisia B-Disease 0
, O 0
was O 0
no O 0
different O 0
with O 0
quetiapine B-Chemical 0
monotherapy O 0
( O 0
12 O 0
. O 0
9 O 0
% O 0
) O 0
than O 0
with O 0
placebo O 0
( O 0
13 O 0
. O 0
1 O 0
% O 0
) O 0
. O 0

Similarly O 0
, O 0
EPS B-Disease 0
- O 0
related O 0
adverse O 0
events O 0
with O 0
QTP B-Chemical 0
+ O 0
Li B-Chemical 0
/ O 0
DVP B-Chemical 0
( O 0
21 O 0
. O 0
4 O 0
% O 0
) O 0
were O 0
no O 0
different O 0
than O 0
with O 0
PBO O 0
+ O 0
Li B-Chemical 0
/ O 0
DVP B-Chemical 0
( O 0
19 O 0
. O 0
2 O 0
% O 0
) O 0
. O 0

Adverse O 0
events O 0
related O 0
to O 0
EPS B-Disease 0
occurred O 0
in O 0
59 O 0
. O 0
6 O 0
% O 0
of O 0
patients O 0
treated O 0
with O 0
haloperidol B-Chemical 0
( O 0
n O 0
= O 0
99 O 0
) O 0
monotherapy O 0
, O 0
whereas O 0
26 O 0
. O 0
5 O 0
% O 0
of O 0
patients O 0
treated O 0
with O 0
lithium B-Chemical 0
( O 0
n O 0
= O 0
98 O 0
) O 0
monotherapy O 0
experienced O 0
adverse O 0
events O 0
related O 0
to O 0
EPS B-Disease 0
. O 0

The O 0
incidence O 0
of O 0
akathisia B-Disease 0
was O 0
low O 0
and O 0
similar O 0
with O 0
quetiapine B-Chemical 0
monotherapy O 0
( O 0
3 O 0
. O 0
3 O 0
% O 0
) O 0
and O 0
placebo O 0
( O 0
6 O 0
. O 0
1 O 0
% O 0
) O 0
, O 0
and O 0
with O 0
QTP B-Chemical 0
+ O 0
Li B-Chemical 0
/ O 0
DVP B-Chemical 0
( O 0
3 O 0
. O 0
6 O 0
% O 0
) O 0
and O 0
PBO O 0
+ O 0
Li B-Chemical 0
/ O 0
DVP B-Chemical 0
( O 0
4 O 0
. O 0
9 O 0
% O 0
) O 0
. O 0

Lithium B-Chemical 0
was O 0
associated O 0
with O 0
a O 0
significantly O 0
higher O 0
incidence O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
of O 0
tremor B-Disease 0
( O 0
18 O 0
. O 0
4 O 0
% O 0
) O 0
than O 0
quetiapine B-Chemical 0
( O 0
5 O 0
. O 0
6 O 0
% O 0
) O 0
; O 0
cerebellar O 0
tremor B-Disease 0
, O 0
which O 0
is O 0
a O 0
known O 0
adverse O 0
effect O 0
of O 0
lithium B-Chemical 0
, O 0
may O 0
have O 0
contributed O 0
to O 0
the O 0
elevated O 0
rate O 0
of O 0
tremor B-Disease 0
in O 0
patients O 0
receiving O 0
lithium B-Chemical 0
therapy O 0
. O 0

Haloperidol B-Chemical 0
induced O 0
a O 0
significantly O 0
higher O 0
incidence O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
of O 0
akathisia B-Disease 0
( O 0
33 O 0
. O 0
3 O 0
% O 0
versus O 0
5 O 0
. O 0
9 O 0
% O 0
) O 0
, O 0
tremor B-Disease 0
( O 0
30 O 0
. O 0
3 O 0
% O 0
versus O 0
7 O 0
. O 0
8 O 0
% O 0
) O 0
, O 0
and O 0
extrapyramidal B-Disease 0
syndrome I-Disease 0
( O 0
35 O 0
. O 0
4 O 0
% O 0
versus O 0
5 O 0
. O 0
9 O 0
% O 0
) O 0
than O 0
quetiapine B-Chemical 0
. O 0

No O 0
significant O 0
differences O 0
were O 0
observed O 0
between O 0
quetiapine B-Chemical 0
and O 0
placebo O 0
on O 0
SAS O 0
and O 0
BARS O 0
scores O 0
. O 0

Anticholinergic O 0
use O 0
was O 0
low O 0
and O 0
similar O 0
with O 0
quetiapine B-Chemical 0
or O 0
placebo O 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
bipolar B-Disease 0
mania I-Disease 0
, O 0
the O 0
incidence O 0
of O 0
EPS B-Disease 0
, O 0
including O 0
akathisia B-Disease 0
, O 0
with O 0
quetiapine B-Chemical 0
therapy O 0
is O 0
similar O 0
to O 0
that O 0
with O 0
placebo O 0
. O 0

Is O 0
phenytoin B-Chemical 0
administration O 0
safe O 0
in O 0
a O 0
hypothermic B-Disease 0
child O 0
? O 0

A O 0
male O 0
neonate O 0
with O 0
a O 0
Chiari B-Disease 0
malformation I-Disease 0
and O 0
a O 0
leaking O 0
myelomeningocoele O 0
underwent O 0
ventriculoperitoneal O 0
shunt O 0
insertion O 0
followed O 0
by O 0
repair O 0
of O 0
myelomeningocoele O 0
. O 0

During O 0
anaesthesia O 0
and O 0
surgery O 0
, O 0
he O 0
inadvertently O 0
became O 0
moderately O 0
hypothermic B-Disease 0
. O 0

Intravenous O 0
phenytoin B-Chemical 0
was O 0
administered O 0
during O 0
the O 0
later O 0
part O 0
of O 0
the O 0
surgery O 0
for O 0
seizure B-Disease 0
prophylaxis O 0
. O 0

Following O 0
phenytoin B-Chemical 0
administration O 0
, O 0
the O 0
patient O 0
developed O 0
acute O 0
severe O 0
bradycardia B-Disease 0
, O 0
refractory O 0
to O 0
atropine B-Chemical 0
and O 0
adrenaline B-Chemical 0
. O 0

The O 0
cardiac O 0
depressant O 0
actions O 0
of O 0
phenytoin B-Chemical 0
and O 0
hypothermia B-Disease 0
can O 0
be O 0
additive O 0
. O 0

Administration O 0
of O 0
phenytoin B-Chemical 0
in O 0
the O 0
presence O 0
of O 0
hypothermia B-Disease 0
may O 0
lead O 0
to O 0
an O 0
adverse O 0
cardiac O 0
event O 0
in O 0
children O 0
. O 0

As O 0
phenytoin B-Chemical 0
is O 0
a O 0
commonly O 0
used O 0
drug O 0
, O 0
clinicians O 0
need O 0
to O 0
be O 0
aware O 0
of O 0
this O 0
interaction O 0
. O 0

Valproate B-Chemical 0
- O 0
induced O 0
chorea B-Disease 0
and O 0
encephalopathy B-Disease 0
in O 0
atypical O 0
nonketotic B-Disease 0
hyperglycinemia I-Disease 0
. O 0

Nonketotic B-Disease 0
hyperglycinemia I-Disease 0
is O 0
a O 0
disorder B-Disease 0
of I-Disease 0
amino I-Disease 0
acid I-Disease 0
metabolism I-Disease 0
in O 0
which O 0
a O 0
defect O 0
in O 0
the O 0
glycine B-Chemical 0
cleavage O 0
system O 0
leads O 0
to O 0
an O 0
accumulation O 0
of O 0
glycine B-Chemical 0
in O 0
the O 0
brain O 0
and O 0
other O 0
body O 0
compartments O 0
. O 0

In O 0
the O 0
classical O 0
form O 0
it O 0
presents O 0
as O 0
neonatal O 0
apnea B-Disease 0
, O 0
intractable O 0
seizures B-Disease 0
, O 0
and O 0
hypotonia B-Disease 0
, O 0
followed O 0
by O 0
significant O 0
psychomotor B-Disease 0
retardation I-Disease 0
. O 0

An O 0
important O 0
subset O 0
of O 0
children O 0
with O 0
nonketotic B-Disease 0
hyperglycinemia I-Disease 0
are O 0
atypical O 0
variants O 0
who O 0
present O 0
in O 0
a O 0
heterogeneous O 0
manner O 0
. O 0

This O 0
report O 0
describes O 0
a O 0
patient O 0
with O 0
mild O 0
language B-Disease 0
delay I-Disease 0
and O 0
mental B-Disease 0
retardation I-Disease 0
, O 0
who O 0
was O 0
found O 0
to O 0
have O 0
nonketotic B-Disease 0
hyperglycinemia I-Disease 0
following O 0
her O 0
presentation O 0
with O 0
acute O 0
encephalopathy B-Disease 0
and O 0
chorea B-Disease 0
shortly O 0
after O 0
initiation O 0
of O 0
valproate B-Chemical 0
therapy O 0
. O 0

Delayed O 0
institution O 0
of O 0
hypertension B-Disease 0
during O 0
focal O 0
cerebral B-Disease 0
ischemia I-Disease 0
: O 0
effect O 0
on O 0
brain B-Disease 0
edema I-Disease 0
. O 0

The O 0
effect O 0
of O 0
induced O 0
hypertension B-Disease 0
instituted O 0
after O 0
a O 0
2 O 0
- O 0
h O 0
delay O 0
following O 0
middle B-Disease 0
cerebral I-Disease 0
artery I-Disease 0
occlusion I-Disease 0
( O 0
MCAO B-Disease 0
) O 0
on O 0
brain B-Disease 0
edema I-Disease 0
formation O 0
and O 0
histochemical O 0
injury O 0
was O 0
studied O 0
. O 0

Under O 0
isoflurane B-Chemical 0
anesthesia O 0
, O 0
the O 0
MCA O 0
of O 0
14 O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
was O 0
occluded O 0
. O 0

In O 0
the O 0
control O 0
group O 0
( O 0
n O 0
= O 0
7 O 0
) O 0
, O 0
the O 0
mean O 0
arterial O 0
pressure O 0
( O 0
MAP O 0
) O 0
was O 0
not O 0
manipulated O 0
. O 0

In O 0
the O 0
hypertensive B-Disease 0
group O 0
( O 0
n O 0
= O 0
7 O 0
) O 0
, O 0
the O 0
MAP O 0
was O 0
elevated O 0
by O 0
25 O 0
- O 0
30 O 0
mm O 0
Hg O 0
beginning O 0
2 O 0
h O 0
after O 0
MCAO B-Disease 0
. O 0

Four O 0
hours O 0
after O 0
MCAO B-Disease 0
, O 0
the O 0
rats O 0
were O 0
killed O 0
and O 0
the O 0
brains O 0
harvested O 0
. O 0

The O 0
brains O 0
were O 0
sectioned O 0
along O 0
coronal O 0
planes O 0
spanning O 0
the O 0
distribution O 0
of O 0
ischemia B-Disease 0
produced O 0
by O 0
MCAO B-Disease 0
. O 0

Specific O 0
gravity O 0
( O 0
SG O 0
) O 0
was O 0
determined O 0
in O 0
the O 0
subcortex O 0
and O 0
in O 0
two O 0
sites O 0
in O 0
the O 0
cortex O 0
( O 0
core O 0
and O 0
periphery O 0
of O 0
the O 0
ischemic B-Disease 0
territory O 0
) O 0
. O 0

The O 0
extent O 0
of O 0
neuronal B-Disease 0
injury I-Disease 0
was O 0
determined O 0
by 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
staining O 0
. O 0

In O 0
the O 0
ischemic B-Disease 0
core O 0
, O 0
there O 0
was O 0
no O 0
difference O 0
in O 0
SG O 0
in O 0
the O 0
subcortex O 0
and O 0
cortex O 0
in O 0
the O 0
two O 0
groups O 0
. O 0

In O 0
the O 0
periphery O 0
of O 0
the O 0
ischemic B-Disease 0
territory O 0
, O 0
SG O 0
in O 0
the O 0
cortex O 0
was O 0
greater O 0
( O 0
less O 0
edema B-Disease 0
accumulation O 0
) O 0
in O 0
the O 0
hypertensive B-Disease 0
group O 0
( O 0
1 O 0
. O 0
041 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
001 O 0
vs O 0
1 O 0
. O 0
039 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
001 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
area O 0
of O 0
histochemical O 0
injury O 0
( O 0
as O 0
a O 0
percent O 0
of O 0
the O 0
cross O 0
- O 0
sectional O 0
area O 0
of O 0
the O 0
hemisphere O 0
) O 0
was O 0
less O 0
in O 0
the O 0
hypertensive B-Disease 0
group O 0
( O 0
33 O 0
+ O 0
/ O 0
- O 0
3 O 0
% O 0
vs O 0
21 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

The O 0
data O 0
indicate O 0
that O 0
phenylephrine B-Chemical 0
- O 0
induced O 0
hypertension B-Disease 0
instituted O 0
2 O 0
h O 0
after O 0
MCAO B-Disease 0
does O 0
not O 0
aggravate O 0
edema B-Disease 0
in O 0
the O 0
ischemic B-Disease 0
core O 0
, O 0
that O 0
it O 0
improves O 0
edema B-Disease 0
in O 0
the O 0
periphery O 0
of O 0
the O 0
ischemic B-Disease 0
territory O 0
, O 0
and O 0
that O 0
it O 0
reduces O 0
the O 0
area O 0
of O 0
histochemical O 0
neuronal B-Disease 0
dysfunction I-Disease 0
. O 0

Behavioral O 0
effects O 0
of O 0
pubertal O 0
anabolic O 0
androgenic O 0
steroid B-Chemical 0
exposure O 0
in O 0
male O 0
rats O 0
with O 0
low O 0
serotonin 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
the O 0
interactive O 0
effects O 0
of O 0
chronic O 0
anabolic O 0
androgenic O 0
steroid B-Chemical 0
( O 0
AAS O 0
) O 0
exposure O 0
and O 0
brain O 0
serotonin B-Chemical 0
( 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
depletion O 0
on O 0
behavior O 0
of O 0
pubertal O 0
male O 0
rats O 0
. O 0

Serotonin B-Chemical 0
was O 0
depleted O 0
beginning O 0
on O 0
postnatal O 0
day O 0
26 O 0
with O 0
parachlorophenylalanine B-Chemical 0
( O 0
PCPA B-Chemical 0
100 O 0
mg O 0
/ O 0
kg O 0
, O 0
every O 0
other O 0
day O 0
) O 0
; O 0
controls O 0
received O 0
saline O 0
. O 0

At O 0
puberty O 0
( O 0
P40 O 0
) O 0
, O 0
half O 0
the O 0
PCPA B-Chemical 0
- O 0
treated O 0
rats O 0
and O 0
half O 0
the O 0
saline O 0
- O 0
treated O 0
rats O 0
began O 0
treatment O 0
with O 0
testosterone B-Chemical 0
( O 0
T B-Chemical 0
, O 0
5 O 0
mg O 0
/ O 0
kg O 0
, O 0
5 O 0
days O 0
/ O 0
week O 0
) O 0
. O 0

Behavioral O 0
measures O 0
included O 0
locomotion O 0
, O 0
irritability B-Disease 0
, O 0
copulation O 0
, O 0
partner O 0
preference O 0
, O 0
and O 0
aggression B-Disease 0
. O 0

Animals O 0
were O 0
tested O 0
for O 0
aggression B-Disease 0
in O 0
their O 0
home O 0
cage O 0
, O 0
both O 0
with O 0
and O 0
without O 0
physical O 0
provocation O 0
( O 0
mild O 0
tail O 0
pinch O 0
) O 0
. O 0

Brain O 0
levels O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
and O 0
its O 0
metabolite O 0
, 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
, O 0
were O 0
determined O 0
using O 0
HPLC O 0
. O 0

PCPA B-Chemical 0
significantly O 0
and O 0
substantially O 0
depleted O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
and O 0
5 B-Chemical 0
- I-Chemical 0
HIAA I-Chemical 0
in O 0
all O 0
brain O 0
regions O 0
examined O 0
. O 0

Chronic O 0
T B-Chemical 0
treatment O 0
significantly O 0
decreased O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
and O 0
5 B-Chemical 0
- I-Chemical 0
HIAA I-Chemical 0
in O 0
certain O 0
brain O 0
areas O 0
, O 0
but O 0
to O 0
a O 0
much O 0
lesser O 0
extent O 0
than O 0
PCPA B-Chemical 0
. O 0

Chronic O 0
exposure O 0
to O 0
PCPA B-Chemical 0
alone O 0
significantly O 0
decreased O 0
locomotor O 0
activity O 0
and O 0
increased O 0
irritability B-Disease 0
but O 0
had O 0
no O 0
effect O 0
on O 0
sexual O 0
behavior O 0
, O 0
partner O 0
preference O 0
, O 0
or O 0
aggression B-Disease 0
. O 0

T B-Chemical 0
alone O 0
had O 0
no O 0
effect O 0
on O 0
locomotion O 0
, O 0
irritability B-Disease 0
, O 0
or O 0
sexual O 0
behavior O 0
but O 0
increased O 0
partner O 0
preference O 0
and O 0
aggression B-Disease 0
. O 0

The O 0
most O 0
striking O 0
effect O 0
of O 0
combining O 0
T B-Chemical 0
+ O 0
PCPA B-Chemical 0
was O 0
a O 0
significant O 0
increase O 0
in O 0
attack O 0
frequency O 0
as O 0
well O 0
as O 0
a O 0
significant O 0
decrease O 0
in O 0
the O 0
latency O 0
to O 0
attack O 0
, O 0
particularly O 0
following O 0
physical O 0
provocation O 0
. O 0

Based O 0
on O 0
these O 0
data O 0
, O 0
it O 0
can O 0
be O 0
speculated O 0
that O 0
pubertal O 0
AAS O 0
users O 0
with O 0
low O 0
central O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
may O 0
be O 0
especially O 0
prone O 0
to O 0
exhibit O 0
aggressive B-Disease 0
behavior I-Disease 0
. O 0

Effects O 0
of O 0
UMB24 B-Chemical 0
and O 0
( O 0
+ O 0
/ O 0
- O 0
) O 0
- O 0
SM B-Chemical 0
21 I-Chemical 0
, O 0
putative O 0
sigma2 O 0
- O 0
preferring O 0
antagonists O 0
, O 0
on O 0
behavioral O 0
toxic O 0
and O 0
stimulant O 0
effects O 0
of O 0
cocaine B-Chemical 0
in O 0
mice O 0
. O 0

Earlier O 0
studies O 0
have O 0
demonstrated O 0
that O 0
antagonism O 0
of O 0
sigma1 O 0
receptors O 0
attenuates O 0
the O 0
convulsive B-Disease 0
, O 0
lethal O 0
, O 0
locomotor O 0
stimulatory O 0
and O 0
rewarding O 0
actions O 0
of O 0
cocaine B-Chemical 0
in O 0
mice O 0
. O 0

In O 0
contrast O 0
, O 0
the O 0
contribution O 0
of O 0
sigma2 O 0
receptors O 0
is O 0
unclear O 0
because O 0
experimental O 0
tools O 0
to O 0
selectively O 0
target O 0
this O 0
subtype O 0
are O 0
unavailable O 0
. O 0

To O 0
begin O 0
addressing O 0
this O 0
need O 0
, O 0
we O 0
characterized O 0
UMB24 B-Chemical 0
( O 0
1 B-Chemical 0
- I-Chemical 0
( I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
phenethyl I-Chemical 0
) I-Chemical 0
- I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
( I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
pyridyl I-Chemical 0
) I-Chemical 0
- I-Chemical 0
piperazine I-Chemical 0
) O 0
and O 0
( O 0
+ O 0
/ O 0
- O 0
) O 0
- O 0
SM B-Chemical 0
21 I-Chemical 0
( O 0
3alpha B-Chemical 0
- I-Chemical 0
tropanyl I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
( I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
chorophenoxy I-Chemical 0
) I-Chemical 0
butyrate I-Chemical 0
) O 0
in O 0
receptor O 0
binding O 0
and O 0
behavioral O 0
studies O 0
. O 0

Receptor O 0
binding O 0
studies O 0
confirmed O 0
that O 0
UMB24 B-Chemical 0
and O 0
( O 0
+ O 0
/ O 0
- O 0
) O 0
- O 0
SM B-Chemical 0
21 I-Chemical 0
display O 0
preferential O 0
affinity O 0
for O 0
sigma2 O 0
over O 0
sigma1 O 0
receptors O 0
. O 0

In O 0
behavioral O 0
studies O 0
, O 0
pretreatment O 0
of O 0
Swiss O 0
Webster O 0
mice O 0
with O 0
UMB24 B-Chemical 0
or O 0
( O 0
+ O 0
/ O 0
- O 0
) O 0
- O 0
SM B-Chemical 0
21 I-Chemical 0
significantly O 0
attenuated O 0
cocaine B-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
and O 0
locomotor O 0
activity O 0
, O 0
but O 0
not O 0
lethality O 0
. O 0

When O 0
administered O 0
alone O 0
, O 0
( O 0
+ O 0
/ O 0
- O 0
) O 0
- O 0
SM B-Chemical 0
21 I-Chemical 0
produced O 0
no O 0
significant O 0
effects O 0
compared O 0
to O 0
control O 0
injections O 0
of O 0
saline O 0
, O 0
but O 0
UMB24 B-Chemical 0
had O 0
locomotor O 0
depressant O 0
actions O 0
. O 0

Together O 0
, O 0
the O 0
data O 0
suggest O 0
that O 0
sigma2 O 0
receptor O 0
antagonists O 0
have O 0
the O 0
potential O 0
to O 0
attenuate O 0
some O 0
of O 0
the O 0
behavioral O 0
effects O 0
of O 0
cocaine B-Chemical 0
, O 0
and O 0
further O 0
development O 0
of O 0
more O 0
selective O 0
, O 0
high O 0
affinity O 0
ligands O 0
are O 0
warranted O 0
. O 0

Cardiac B-Disease 0
arrest I-Disease 0
in O 0
a O 0
child O 0
with O 0
cerebral B-Disease 0
palsy I-Disease 0
undergoing O 0
sevoflurane B-Chemical 0
induction O 0
of O 0
anesthesia O 0
after O 0
preoperative O 0
clonidine B-Chemical 0
. O 0

Clonidine B-Chemical 0
is O 0
a O 0
frequently O 0
administered O 0
alpha2 O 0
- O 0
adrenergic O 0
agonist O 0
which O 0
can O 0
decrease O 0
heart O 0
rate O 0
and O 0
blood O 0
pressure O 0
. O 0

We O 0
present O 0
a O 0
case O 0
of O 0
a O 0
5 O 0
- O 0
year O 0
- O 0
old O 0
child O 0
with O 0
cerebral B-Disease 0
palsy I-Disease 0
and O 0
seizure B-Disease 0
disorder I-Disease 0
, O 0
receiving O 0
clonidine B-Chemical 0
for O 0
restlessness B-Disease 0
, O 0
who O 0
presented O 0
for O 0
placement O 0
of O 0
a O 0
baclofen B-Chemical 0
pump O 0
. O 0

Without O 0
the O 0
knowledge O 0
of O 0
the O 0
medical O 0
personnel O 0
, O 0
the O 0
patient O 0
' O 0
s O 0
mother O 0
administered O 0
three O 0
doses O 0
of O 0
clonidine B-Chemical 0
during O 0
the O 0
evening O 0
before O 0
and O 0
morning O 0
of O 0
surgery O 0
to O 0
reduce O 0
anxiety B-Disease 0
. O 0

During O 0
induction O 0
of O 0
anesthesia O 0
, O 0
the O 0
patient O 0
developed O 0
bradycardia B-Disease 0
and O 0
hypotension B-Disease 0
requiring O 0
cardiac O 0
resuscitation O 0
. O 0

There O 0
are O 0
no O 0
previous O 0
reports O 0
of O 0
clonidine B-Chemical 0
- O 0
associated O 0
cardiac B-Disease 0
arrest I-Disease 0
in O 0
a O 0
child O 0
undergoing O 0
induction O 0
of O 0
anesthesia O 0
. O 0

Angiotensin O 0
- O 0
converting O 0
enzyme O 0
( O 0
ACE O 0
) O 0
inhibitor O 0
- O 0
associated O 0
angioedema B-Disease 0
of O 0
the O 0
stomach O 0
and O 0
small O 0
intestine O 0
: O 0
a O 0
case O 0
report O 0
. O 0

This O 0
is O 0
a O 0
case O 0
report O 0
on O 0
a O 0
45 O 0
- O 0
year O 0
old O 0
African O 0
- O 0
American O 0
female O 0
with O 0
newly O 0
diagnosed O 0
hypertension B-Disease 0
, O 0
who O 0
was O 0
started O 0
on O 0
a O 0
combination O 0
pill O 0
of O 0
amlodipine B-Chemical 0
/ O 0
benazapril B-Chemical 0
10 O 0
/ O 0
5 O 0
mg O 0
. O 0

The O 0
very O 0
next O 0
day O 0
, O 0
she O 0
presented O 0
at O 0
the O 0
emergency O 0
room O 0
( O 0
ER O 0
) O 0
with O 0
abdominal B-Disease 0
pain I-Disease 0
, O 0
nausea B-Disease 0
and O 0
vomiting B-Disease 0
. O 0

Physical O 0
exam O 0
, O 0
complete O 0
metabolic O 0
panel O 0
, O 0
and O 0
hemogram O 0
were O 0
in O 0
the O 0
normal O 0
range O 0
. O 0

She O 0
was O 0
discharged O 0
from O 0
the O 0
ER O 0
after O 0
a O 0
few O 0
hours O 0
of O 0
treatment O 0
with O 0
fluid O 0
and O 0
analgesics O 0
. O 0

However O 0
, O 0
she O 0
returned O 0
to O 0
the O 0
ER O 0
the O 0
next O 0
day O 0
with O 0
the O 0
same O 0
complaints O 0
. O 0

This O 0
time O 0
the O 0
physical O 0
exam O 0
was O 0
significant O 0
for O 0
a O 0
distended O 0
abdomen O 0
with O 0
dullness O 0
to O 0
percussion O 0
. O 0

CT O 0
scan O 0
of O 0
the O 0
abdomen O 0
revealed O 0
markedly O 0
thickened O 0
antrum O 0
of O 0
the O 0
stomach O 0
, O 0
duodenum O 0
and O 0
jejunum O 0
, O 0
along O 0
with O 0
fluid O 0
in O 0
the O 0
abdominal O 0
and O 0
pelvic O 0
cavity O 0
. O 0

Angiotensin O 0
- O 0
converting O 0
enzyme O 0
inhibitor O 0
( O 0
ACEI O 0
) O 0
- O 0
induced O 0
angioedema B-Disease 0
was O 0
suspected O 0
, O 0
and O 0
anti O 0
- O 0
hypertensive B-Disease 0
medications O 0
were O 0
discontinued O 0
. O 0

Her O 0
symptoms O 0
improved O 0
within O 0
the O 0
next O 0
24 O 0
hours O 0
, O 0
and O 0
repeat O 0
CT O 0
after O 0
72 O 0
hours O 0
revealed O 0
marked O 0
improvement O 0
in O 0
stomach O 0
and O 0
small O 0
bowel O 0
thickening O 0
and O 0
resolution O 0
of O 0
ascites B-Disease 0
. O 0

The O 0
recognition O 0
of O 0
angiotensin B-Chemical 0
- O 0
converting O 0
enzyme O 0
( O 0
ACE O 0
) O 0
and O 0
angiotensin B-Chemical 0
receptor O 0
blocker O 0
( O 0
ARB O 0
) O 0
intestinal B-Disease 0
angioedema I-Disease 0
constitutes O 0
a O 0
challenge O 0
to O 0
primary O 0
care O 0
physicians O 0
, O 0
internists O 0
, O 0
emergency O 0
room O 0
personal O 0
and O 0
surgeons O 0
. O 0

Carbamazepine B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
dysfunction I-Disease 0
. O 0

Characterization O 0
of O 0
two O 0
distinct O 0
clinical O 0
syndromes O 0
. O 0

A O 0
patient O 0
with O 0
sinus O 0
bradycardia B-Disease 0
and O 0
atrioventricular B-Disease 0
block I-Disease 0
, O 0
induced O 0
by O 0
carbamazepine B-Chemical 0
, O 0
prompted O 0
an O 0
extensive O 0
literature O 0
review O 0
of O 0
all O 0
previously O 0
reported O 0
cases O 0
. O 0

From O 0
the O 0
analysis O 0
of O 0
these O 0
cases O 0
, O 0
two O 0
distinct O 0
forms O 0
of O 0
carbamazepine B-Chemical 0
- O 0
associated O 0
cardiac B-Disease 0
dysfunction I-Disease 0
emerged O 0
. O 0

One O 0
patient O 0
group O 0
developed O 0
sinus B-Disease 0
tachycardias I-Disease 0
in O 0
the O 0
setting O 0
of O 0
a O 0
massive O 0
carbamazepine B-Chemical 0
overdose B-Disease 0
. O 0

The O 0
second O 0
group O 0
consisted O 0
almost O 0
exclusively O 0
of O 0
elderly O 0
women O 0
who O 0
developed O 0
potentially O 0
life O 0
- O 0
threatening O 0
bradyarrhythmias B-Disease 0
or O 0
atrioventricular B-Disease 0
conduction I-Disease 0
delay I-Disease 0
, O 0
associated O 0
with O 0
either O 0
therapeutic O 0
or O 0
modestly O 0
elevated O 0
carbamazepine B-Chemical 0
serum O 0
levels O 0
. O 0

Because O 0
carbamazepine B-Chemical 0
is O 0
widely O 0
used O 0
in O 0
the O 0
treatment O 0
of O 0
many O 0
neurologic O 0
and O 0
psychiatric B-Disease 0
conditions O 0
, O 0
the O 0
recognition O 0
of O 0
the O 0
latter O 0
syndrome O 0
has O 0
important O 0
implications O 0
for O 0
the O 0
use O 0
of O 0
this O 0
drug O 0
in O 0
elderly O 0
patients O 0
. O 0

Detection O 0
of O 0
abnormal O 0
cardiac O 0
adrenergic O 0
neuron O 0
activity O 0
in O 0
adriamycin B-Chemical 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
with O 0
iodine B-Chemical 0
- I-Chemical 0
125 I-Chemical 0
- I-Chemical 0
metaiodobenzylguanidine I-Chemical 0
. O 0

Radiolabeled B-Chemical 0
metaiodobenzylguanidine I-Chemical 0
( O 0
MIBG B-Chemical 0
) O 0
, O 0
an O 0
analog O 0
of O 0
norepinephrine B-Chemical 0
( O 0
NE B-Chemical 0
) O 0
, O 0
serves O 0
as O 0
an O 0
index O 0
of O 0
adrenergic O 0
neuron O 0
integrity O 0
and O 0
function O 0
. O 0

Using O 0
a O 0
rat O 0
model O 0
of O 0
adriamycin B-Chemical 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
, O 0
we O 0
tested O 0
the O 0
hypothesis O 0
that O 0
abnormal O 0
cardiac O 0
adrenergic O 0
neuron O 0
activity O 0
may O 0
appear O 0
and O 0
be O 0
exacerbated O 0
dose O 0
- O 0
dependently O 0
in O 0
adriamycin B-Chemical 0
cardiomyopathy B-Disease 0
. O 0

The O 0
degree O 0
of O 0
vacuolar B-Disease 0
degeneration I-Disease 0
of I-Disease 0
myocardial I-Disease 0
cells I-Disease 0
was O 0
analyzed O 0
in O 0
relation O 0
to O 0
the O 0
duration O 0
of O 0
adriamycin B-Chemical 0
treatment O 0
( O 0
2 O 0
mg O 0
/ O 0
kg O 0
, O 0
once O 0
a O 0
week O 0
) O 0
. O 0

There O 0
were O 0
no O 0
abnormalities O 0
or O 0
only O 0
isolated O 0
degeneration O 0
in O 0
the O 0
1 O 0
- O 0
or O 0
2 O 0
- O 0
wk O 0
treatment O 0
groups O 0
, O 0
isolated O 0
or O 0
scattered O 0
degeneration O 0
in O 0
half O 0
of O 0
the O 0
3 O 0
- O 0
wk O 0
group O 0
, O 0
frequent O 0
scattered O 0
degeneration O 0
in O 0
the O 0
4 O 0
- O 0
wk O 0
group O 0
, O 0
scattered O 0
or O 0
focal O 0
degeneration O 0
in O 0
the O 0
5 O 0
- O 0
wk O 0
group O 0
, O 0
and O 0
extensive O 0
degeneration O 0
in O 0
the O 0
8 O 0
- O 0
wk O 0
group O 0
. O 0

Myocardial O 0
accumulation O 0
of O 0
[ O 0
125I O 0
] O 0
MIBG B-Chemical 0
4 O 0
hr O 0
after O 0
intravenous O 0
injection O 0
did O 0
not O 0
differ O 0
between O 0
the O 0
controls O 0
and O 0
the O 0
groups O 0
treated O 0
3 O 0
wk O 0
or O 0
less O 0
. O 0

However O 0
, O 0
the O 0
4 O 0
- O 0
wk O 0
group O 0
had O 0
a O 0
slightly O 0
lower O 0
accumulation O 0
in O 0
the O 0
right O 0
ventricular O 0
wall O 0
( O 0
82 O 0
% O 0
of O 0
the O 0
control O 0
) O 0
and O 0
significantly O 0
lower O 0
accumulation O 0
in O 0
the O 0
left O 0
ventricular O 0
wall O 0
( O 0
about O 0
66 O 0
% O 0
of O 0
the O 0
control 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
the O 0
5 O 0
- O 0
wk O 0
group O 0
, O 0
MIBG B-Chemical 0
accumulation O 0
in O 0
the O 0
right O 0
and O 0
left O 0
ventricular O 0
wall O 0
was O 0
35 O 0
% O 0
and O 0
27 O 0
% O 0
of O 0
that O 0
in O 0
controls O 0
, O 0
respectively 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

In O 0
the O 0
8 O 0
- O 0
wk O 0
group O 0
, O 0
MIBG B-Chemical 0
accumulation O 0
in O 0
the O 0
right O 0
and O 0
left O 0
ventricular O 0
wall O 0
was O 0
18 O 0
% O 0
and O 0
14 O 0
% O 0
of O 0
that O 0
in O 0
controls O 0
, O 0
respectively 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
MIBG B-Chemical 0
accumulation O 0
in O 0
the O 0
myocardium O 0
decreased O 0
in O 0
an O 0
adriamycin B-Chemical 0
dose O 0
- O 0
dependent O 0
manner O 0
. O 0

The O 0
appearance O 0
of O 0
impaired O 0
cardiac O 0
adrenergic O 0
neuron O 0
activity O 0
in O 0
the O 0
presence O 0
of O 0
slight O 0
myocardial B-Disease 0
impairment I-Disease 0
( O 0
scattered O 0
or O 0
focal O 0
vacuolar B-Disease 0
degeneration I-Disease 0
) O 0
indicates O 0
that O 0
MIBG B-Chemical 0
scintigraphy O 0
may O 0
be O 0
a O 0
useful O 0
method O 0
for O 0
detection O 0
of O 0
adriamycin B-Chemical 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
. O 0

Syncope B-Disease 0
and O 0
QT B-Disease 0
prolongation I-Disease 0
among O 0
patients O 0
treated O 0
with O 0
methadone B-Chemical 0
for O 0
heroin B-Chemical 0
dependence O 0
in O 0
the O 0
city O 0
of O 0
Copenhagen O 0
. O 0

BACKGROUND O 0
: O 0
Methadone B-Chemical 0
is O 0
prescribed O 0
to O 0
heroin B-Chemical 0
addicts O 0
to O 0
decrease O 0
illicit O 0
opioid O 0
use O 0
. O 0

Prolongation O 0
of O 0
the O 0
QT O 0
interval O 0
in O 0
the O 0
ECG O 0
of O 0
patients O 0
with O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
( O 0
TdP B-Disease 0
) O 0
has O 0
been O 0
reported O 0
in O 0
methadone B-Chemical 0
users O 0
. O 0

As O 0
heroin B-Chemical 0
addicts O 0
sometimes O 0
faint O 0
while O 0
using O 0
illicit O 0
drugs O 0
, O 0
doctors O 0
might O 0
attribute O 0
too O 0
many O 0
episodes O 0
of O 0
syncope B-Disease 0
to O 0
illicit O 0
drug O 0
use O 0
and O 0
thereby O 0
underestimate O 0
the O 0
incidence O 0
of O 0
TdP B-Disease 0
in O 0
this O 0
special O 0
population O 0
, O 0
and O 0
the O 0
high O 0
mortality O 0
in O 0
this O 0
population O 0
may O 0
, O 0
in O 0
part O 0
, O 0
be O 0
caused O 0
by O 0
the O 0
proarrhythmic O 0
effect O 0
of O 0
methadone B-Chemical 0
. O 0

METHODS O 0
: O 0
In O 0
this O 0
cross O 0
- O 0
sectional O 0
study O 0
interview O 0
, O 0
ECGs O 0
and O 0
blood O 0
samples O 0
were O 0
collected O 0
in O 0
a O 0
population O 0
of O 0
adult O 0
heroin B-Chemical 0
addicts O 0
treated O 0
with O 0
methadone B-Chemical 0
or O 0
buprenorphine B-Chemical 0
on O 0
a O 0
daily O 0
basis O 0
. O 0

Of O 0
the O 0
patients O 0
at O 0
the O 0
Drug O 0
Addiction O 0
Service O 0
in O 0
the O 0
municipal O 0
of O 0
Copenhagen O 0
, O 0
450 O 0
( O 0
approximately O 0
52 O 0
% O 0
) O 0
were O 0
included O 0
. O 0

The O 0
QT O 0
interval O 0
was O 0
estimated O 0
from O 0
12 O 0
lead O 0
ECGs O 0
. O 0

All O 0
participants O 0
were O 0
interviewed O 0
about O 0
any O 0
experience O 0
of O 0
syncope B-Disease 0
. O 0

The O 0
association O 0
between O 0
opioid O 0
dose O 0
and O 0
QT O 0
, O 0
and O 0
methadone B-Chemical 0
dose O 0
and O 0
reporting O 0
of O 0
syncope B-Disease 0
was O 0
assessed O 0
using O 0
multivariate O 0
linear O 0
regression O 0
and O 0
logistic O 0
regression O 0
, O 0
respectively O 0
. O 0

RESULTS O 0
: O 0
Methadone B-Chemical 0
dose O 0
was O 0
associated O 0
with O 0
longer O 0
QT O 0
interval O 0
of O 0
0 O 0
. O 0
140 O 0
ms O 0
/ O 0
mg O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
002 O 0
) O 0
. O 0

No O 0
association O 0
between O 0
buprenorphine B-Chemical 0
and O 0
QTc O 0
was O 0
found O 0
. O 0

Among O 0
the O 0
subjects O 0
treated O 0
with O 0
methadone B-Chemical 0
, O 0
28 O 0
% O 0
men O 0
and O 0
32 O 0
% O 0
women O 0
had O 0
prolonged B-Disease 0
QTc I-Disease 0
interval I-Disease 0
. O 0

None O 0
of O 0
the O 0
subjects O 0
treated O 0
with O 0
buprenorphine B-Chemical 0
had O 0
QTc O 0
interval O 0
> O 0
0 O 0
. O 0
440 O 0
s O 0
( O 0
( O 0
1 O 0
/ O 0
2 O 0
) O 0
) O 0
. O 0

A O 0
50 O 0
mg O 0
higher O 0
methadone B-Chemical 0
dose O 0
was O 0
associated O 0
with O 0
a O 0
1 O 0
. O 0
2 O 0
( O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
1 O 0
to O 0
1 O 0
. O 0
4 O 0
) O 0
times O 0
higher O 0
odds O 0
for O 0
syncope B-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
Methadone B-Chemical 0
is O 0
associated O 0
with O 0
QT B-Disease 0
prolongation I-Disease 0
and O 0
higher O 0
reporting O 0
of O 0
syncope B-Disease 0
in O 0
a O 0
population O 0
of O 0
heroin B-Chemical 0
addicts O 0
. O 0

Neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
induced O 0
by O 0
ziprasidone B-Chemical 0
on O 0
the O 0
second O 0
day O 0
of O 0
treatment O 0
. O 0

Neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
( O 0
NMS B-Disease 0
) O 0
is O 0
the O 0
rarest O 0
and O 0
most O 0
serious O 0
of O 0
the O 0
neuroleptic O 0
- O 0
induced O 0
movement B-Disease 0
disorders I-Disease 0
. O 0

We O 0
describe O 0
a O 0
case O 0
of O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
( O 0
NMS B-Disease 0
) O 0
associated O 0
with O 0
the O 0
use O 0
of O 0
ziprasidone B-Chemical 0
. O 0

Although O 0
conventional O 0
neuroleptics O 0
are O 0
more O 0
frequently O 0
associated O 0
with O 0
NMS B-Disease 0
, O 0
atypical O 0
antipsychotic O 0
drugs O 0
like O 0
ziprasidone B-Chemical 0
may O 0
also O 0
be O 0
a O 0
cause O 0
. O 0

The O 0
patient O 0
is O 0
a O 0
24 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
with O 0
a O 0
history O 0
of O 0
schizophrenia B-Disease 0
who O 0
developed O 0
signs O 0
and O 0
symptoms O 0
of O 0
NMS B-Disease 0
after O 0
2 O 0
days O 0
of O 0
treatment O 0
with O 0
an O 0
80 O 0
- O 0
mg O 0
/ O 0
day O 0
dose O 0
of O 0
orally O 0
administrated O 0
ziprasidone B-Chemical 0
. O 0

This O 0
case O 0
is O 0
the O 0
earliest O 0
( O 0
second O 0
day O 0
of O 0
treatment O 0
) O 0
NMS B-Disease 0
due O 0
to O 0
ziprasidone B-Chemical 0
reported O 0
in O 0
the O 0
literature O 0
. O 0

Peripheral O 0
iron B-Chemical 0
dextran I-Chemical 0
induced O 0
degeneration B-Disease 0
of I-Disease 0
dopaminergic I-Disease 0
neurons I-Disease 0
in O 0
rat O 0
substantia O 0
nigra O 0
. O 0

Iron B-Chemical 0
accumulation O 0
is O 0
considered O 0
to O 0
be O 0
involved O 0
in O 0
the O 0
pathogenesis O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

To O 0
demonstrate O 0
the O 0
relationship O 0
between O 0
peripheral O 0
iron B-Chemical 0
overload O 0
and O 0
dopaminergic O 0
neuron O 0
loss O 0
in O 0
rat O 0
substantia O 0
nigra O 0
( O 0
SN O 0
) O 0
, O 0
in O 0
the O 0
present O 0
study O 0
we O 0
used O 0
fast O 0
cyclic O 0
voltammetry O 0
, O 0
tyrosine B-Chemical 0
hydroxylase O 0
( O 0
TH O 0
) O 0
immunohistochemistry O 0
, O 0
Perls O 0
' O 0
iron B-Chemical 0
staining O 0
, O 0
and O 0
high O 0
performance O 0
liquid O 0
chromatography O 0
- O 0
electrochemical O 0
detection O 0
to O 0
study O 0
the O 0
degeneration B-Disease 0
of I-Disease 0
dopaminergic I-Disease 0
neurons I-Disease 0
and O 0
increased O 0
iron B-Chemical 0
content O 0
in O 0
the O 0
SN O 0
of O 0
iron B-Chemical 0
dextran I-Chemical 0
overloaded O 0
animals O 0
. O 0

The O 0
findings O 0
showed O 0
that O 0
peripheral O 0
iron B-Chemical 0
dextran I-Chemical 0
overload O 0
increased O 0
the O 0
iron B-Chemical 0
staining O 0
positive O 0
cells O 0
and O 0
reduced O 0
the O 0
number O 0
of O 0
TH O 0
- O 0
immunoreactive O 0
neurons O 0
in O 0
the O 0
SN O 0
. O 0

As O 0
a O 0
result O 0
, O 0
dopamine B-Chemical 0
release O 0
and O 0
content O 0
, O 0
as O 0
well O 0
as O 0
its O 0
metabolites O 0
contents O 0
were O 0
decreased O 0
in O 0
caudate O 0
putamen O 0
. O 0

Even O 0
more O 0
dramatic O 0
changes O 0
were O 0
found O 0
in O 0
chronic O 0
overload O 0
group O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
peripheral O 0
iron B-Chemical 0
dextran I-Chemical 0
can O 0
increase O 0
the O 0
iron B-Chemical 0
level O 0
in O 0
the O 0
SN O 0
, O 0
where O 0
excessive O 0
iron B-Chemical 0
causes O 0
the O 0
degeneration B-Disease 0
of I-Disease 0
dopaminergic I-Disease 0
neurons I-Disease 0
. O 0

The O 0
chronic O 0
iron B-Chemical 0
overload O 0
may O 0
be O 0
more O 0
destructive O 0
to O 0
dopaminergic O 0
neurons O 0
than O 0
the O 0
acute O 0
iron B-Chemical 0
overload O 0
. O 0

Attenuated O 0
disruption O 0
of O 0
prepulse O 0
inhibition O 0
by O 0
dopaminergic O 0
stimulation O 0
after O 0
maternal O 0
deprivation O 0
and O 0
adolescent O 0
corticosterone B-Chemical 0
treatment O 0
in O 0
rats O 0
. O 0

The O 0
development O 0
of O 0
schizophrenia B-Disease 0
may O 0
include O 0
an O 0
early O 0
neurodevelopmental O 0
stress O 0
component O 0
which O 0
increases O 0
vulnerability O 0
to O 0
later O 0
stressful O 0
life O 0
events O 0
, O 0
in O 0
combination O 0
leading O 0
to O 0
overt O 0
disease O 0
. O 0

We O 0
investigated O 0
the O 0
effect O 0
of O 0
an O 0
early O 0
stress O 0
, O 0
in O 0
the O 0
form O 0
of O 0
maternal O 0
deprivation O 0
, O 0
combined O 0
with O 0
a O 0
later O 0
stress O 0
, O 0
simulated O 0
by O 0
chronic O 0
periadolescent O 0
corticosterone B-Chemical 0
treatment O 0
, O 0
on O 0
behaviour O 0
in O 0
rats O 0
. O 0

Acute O 0
treatment O 0
with O 0
apomorphine B-Chemical 0
caused O 0
disruption O 0
of O 0
prepulse O 0
inhibition O 0
( O 0
PPI O 0
) O 0
in O 0
controls O 0
and O 0
in O 0
rats O 0
that O 0
had O 0
undergone O 0
either O 0
maternal O 0
deprivation O 0
or O 0
corticosterone B-Chemical 0
treatment O 0
, O 0
but O 0
was O 0
surprisingly O 0
absent O 0
in O 0
rats O 0
that O 0
had O 0
undergone O 0
the O 0
combined O 0
early O 0
and O 0
late O 0
stress O 0
. O 0

Amphetamine B-Chemical 0
treatment O 0
significantly O 0
disrupted O 0
PPI O 0
in O 0
both O 0
non O 0
- O 0
deprived O 0
groups O 0
, O 0
but O 0
was O 0
absent O 0
in O 0
both O 0
maternally O 0
deprived O 0
groups O 0
. O 0

The O 0
serotonin B-Chemical 0
- O 0
1A O 0
receptor O 0
agonist O 0
, O 0
8 B-Chemical 0
- I-Chemical 0
OH I-Chemical 0
- I-Chemical 0
DPAT I-Chemical 0
, O 0
induced O 0
a O 0
significant O 0
disruption O 0
of O 0
PPI O 0
in O 0
all O 0
groups O 0
. O 0

Amphetamine B-Chemical 0
- O 0
induced O 0
locomotor B-Disease 0
hyperactivity I-Disease 0
was O 0
similar O 0
in O 0
all O 0
groups O 0
. O 0

These O 0
results O 0
show O 0
an O 0
inhibitory O 0
interaction O 0
of O 0
early O 0
stress O 0
, O 0
caused O 0
by O 0
maternal O 0
deprivation O 0
, O 0
combined O 0
with O 0
' O 0
adolescent O 0
' O 0
stress O 0
, O 0
simulated O 0
by O 0
corticosterone B-Chemical 0
treatment O 0
, O 0
on O 0
dopaminergic O 0
regulation O 0
of O 0
PPI O 0
. O 0

The O 0
altered O 0
effects O 0
of O 0
apomorphine B-Chemical 0
and O 0
amphetamine B-Chemical 0
could O 0
indicate O 0
differential O 0
changes O 0
in O 0
dopamine B-Chemical 0
receptor O 0
signalling O 0
leading O 0
to O 0
functional O 0
desensitisation O 0
, O 0
or O 0
altered O 0
modulation O 0
of O 0
sensory O 0
gating O 0
in O 0
the O 0
nucleus O 0
accumbens O 0
by O 0
limbic O 0
structures O 0
such O 0
as O 0
the O 0
hippocampus O 0
. O 0

An O 0
extremely O 0
rare O 0
case O 0
of O 0
delusional B-Disease 0
parasitosis I-Disease 0
in O 0
a O 0
chronic B-Disease 0
hepatitis I-Disease 0
C I-Disease 0
patient O 0
during O 0
pegylated B-Chemical 0
interferon I-Chemical 0
alpha I-Chemical 0
- I-Chemical 0
2b I-Chemical 0
and O 0
ribavirin B-Chemical 0
treatment O 0
. O 0

During O 0
treatment O 0
of O 0
chronic B-Disease 0
hepatitis I-Disease 0
C I-Disease 0
patients O 0
with O 0
interferon O 0
and O 0
ribavirin B-Chemical 0
, O 0
a O 0
lot O 0
of O 0
side O 0
effects O 0
are O 0
described O 0
. O 0

Twenty O 0
- O 0
three O 0
percent O 0
to O 0
44 O 0
% O 0
of O 0
patients O 0
develop O 0
depression B-Disease 0
. O 0

A O 0
minority O 0
of O 0
patients O 0
evolve O 0
to O 0
psychosis B-Disease 0
. O 0

To O 0
the O 0
best O 0
of O 0
our O 0
knowledge O 0
, O 0
no O 0
cases O 0
of O 0
psychogenic B-Disease 0
parasitosis I-Disease 0
occurring O 0
during O 0
interferon O 0
therapy O 0
have O 0
been O 0
described O 0
in O 0
the O 0
literature O 0
. O 0

We O 0
present O 0
a O 0
49 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
who O 0
developed O 0
a O 0
delusional B-Disease 0
parasitosis I-Disease 0
during O 0
treatment O 0
with O 0
pegylated B-Chemical 0
interferon I-Chemical 0
alpha I-Chemical 0
- I-Chemical 0
2b I-Chemical 0
weekly O 0
and O 0
ribavirin B-Chemical 0
. O 0

She O 0
complained O 0
of O 0
seeing O 0
parasites O 0
and O 0
the O 0
larvae O 0
of O 0
fleas O 0
in O 0
her O 0
stools O 0
. O 0

This O 0
could O 0
not O 0
be O 0
confirmed O 0
by O 0
any O 0
technical O 0
examination O 0
. O 0

All O 0
the O 0
complaints O 0
disappeared O 0
after O 0
stopping O 0
pegylated B-Chemical 0
interferon I-Chemical 0
alpha I-Chemical 0
- I-Chemical 0
2b I-Chemical 0
and O 0
reappeared O 0
after O 0
restarting O 0
it O 0
. O 0

She O 0
had O 0
a O 0
complete O 0
sustained O 0
viral O 0
response O 0
. O 0

Hepatonecrosis B-Disease 0
and O 0
cholangitis B-Disease 0
related O 0
to O 0
long O 0
- O 0
term O 0
phenobarbital B-Chemical 0
therapy O 0
: O 0
an O 0
autopsy O 0
report O 0
of O 0
two O 0
patients O 0
. O 0

Phenobarbital B-Chemical 0
( O 0
PB B-Chemical 0
) O 0
has O 0
a O 0
reputation O 0
for O 0
safety O 0
, O 0
and O 0
it O 0
is O 0
commonly O 0
believed O 0
that O 0
PB B-Chemical 0
- O 0
related O 0
increases O 0
in O 0
serum O 0
aminotransferase O 0
levels O 0
do O 0
not O 0
indicate O 0
or O 0
predict O 0
the O 0
development O 0
of O 0
significant O 0
chronic O 0
liver B-Disease 0
disease I-Disease 0
. O 0

Here O 0
we O 0
report O 0
of O 0
two O 0
adult O 0
patients O 0
with O 0
a O 0
long O 0
history O 0
of O 0
epilepsy B-Disease 0
treated O 0
with O 0
PB B-Chemical 0
who O 0
died O 0
suddenly O 0
: O 0
one O 0
as O 0
consequence O 0
of O 0
cardiac B-Disease 0
arrest I-Disease 0
, O 0
the O 0
other O 0
of O 0
acute O 0
bronchopneumonia B-Disease 0
. O 0

At O 0
autopsy O 0
, O 0
analysis O 0
of O 0
liver O 0
parenchyma O 0
revealed O 0
rich O 0
portal O 0
inflammatory O 0
infiltrate O 0
, O 0
which O 0
consisted O 0
of O 0
mixed O 0
eosinophil O 0
and O 0
monocyte O 0
cells O 0
, O 0
associated O 0
with O 0
several O 0
foci O 0
of O 0
necrosis B-Disease 0
surrounded O 0
by O 0
a O 0
hard O 0
ring O 0
of O 0
non O 0
- O 0
specific O 0
granulomatous O 0
tissue O 0
. O 0

Inflammatory O 0
reactions O 0
of O 0
internal O 0
and O 0
external O 0
hepatic O 0
biliary O 0
ducts O 0
were O 0
also O 0
seen O 0
. O 0

Our O 0
findings O 0
illustrate O 0
that O 0
PB B-Chemical 0
may O 0
be O 0
associated O 0
with O 0
chronic O 0
liver B-Disease 0
damage I-Disease 0
, O 0
which O 0
may O 0
lead O 0
to O 0
more O 0
serious O 0
and O 0
deleterious O 0
consequences O 0
. O 0

For O 0
this O 0
reason O 0
, O 0
each O 0
clinician O 0
should O 0
recognize O 0
this O 0
entity O 0
in O 0
the O 0
differential O 0
diagnosis O 0
of O 0
PB B-Chemical 0
- O 0
related O 0
asymptomatic O 0
chronic B-Disease 0
hepatic I-Disease 0
enzyme I-Disease 0
dysfunction I-Disease 0
. O 0

Delayed O 0
leukoencephalopathy B-Disease 0
with O 0
stroke B-Disease 0
- O 0
like O 0
presentation O 0
in O 0
chemotherapy O 0
recipients O 0
. O 0

BACKGROUND O 0
: O 0
A O 0
transient O 0
leukoencephalopathy B-Disease 0
mimicking O 0
cerebrovascular B-Disease 0
accident I-Disease 0
has O 0
been O 0
described O 0
as O 0
a O 0
complication O 0
of O 0
chemotherapy O 0
, O 0
most O 0
commonly O 0
in O 0
recipients O 0
of O 0
intrathecal O 0
methotrexate B-Chemical 0
for O 0
childhood O 0
leukaemia B-Disease 0
. O 0

Recently O 0
published O 0
neuroimaging O 0
data O 0
suggest O 0
a O 0
common O 0
pathophysiology O 0
associated O 0
with O 0
a O 0
variety O 0
of O 0
chemotherapy O 0
agents O 0
and O 0
modes O 0
of O 0
administration O 0
. O 0

METHODS O 0
: O 0
We O 0
reviewed O 0
the O 0
medical O 0
literature O 0
for O 0
single O 0
reports O 0
and O 0
case O 0
series O 0
of O 0
patients O 0
presenting O 0
with O 0
stroke B-Disease 0
- O 0
like O 0
episodes O 0
while O 0
receiving O 0
systemic O 0
or O 0
intrathecal O 0
chemotherapy O 0
. O 0

We O 0
only O 0
included O 0
studies O 0
providing O 0
detailed O 0
neuroimaging O 0
data O 0
. O 0

Patients O 0
with O 0
cerebrovascular B-Disease 0
accidents I-Disease 0
were O 0
excluded O 0
. O 0

RESULTS O 0
: O 0
We O 0
identified O 0
27 O 0
reports O 0
of O 0
toxic O 0
leukoencephalopathy B-Disease 0
in O 0
patients O 0
treated O 0
with O 0
methotrexate B-Chemical 0
( O 0
intrathecal O 0
, O 0
systemic O 0
) O 0
, O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
and O 0
its O 0
derivative O 0
carmofur B-Chemical 0
, O 0
and O 0
capecitabine B-Chemical 0
. O 0

Diffusion O 0
weighted O 0
imaging O 0
( O 0
DWI O 0
) O 0
of O 0
all O 0
patients O 0
revealed O 0
well O 0
demarcated O 0
hyperintense O 0
lesions B-Disease 0
within I-Disease 0
the I-Disease 0
subcortical I-Disease 0
white I-Disease 0
matter I-Disease 0
of O 0
the O 0
cerebral O 0
hemispheres O 0
and O 0
the O 0
corpus O 0
callosum O 0
, O 0
corresponding O 0
to O 0
areas O 0
of O 0
decreased O 0
proton O 0
diffusion O 0
on O 0
apparent O 0
diffusion O 0
coefficient O 0
( O 0
ADC O 0
) O 0
maps O 0
( O 0
available O 0
in O 0
21 O 0
/ O 0
27 O 0
patients O 0
) O 0
. O 0

Lesions O 0
exceeded O 0
the O 0
confines O 0
of O 0
adjacent O 0
vascular O 0
territories O 0
. O 0

Complete O 0
resolution O 0
of O 0
symptoms O 0
within O 0
1 O 0
- O 0
4 O 0
days O 0
was O 0
accompanied O 0
by O 0
normalisation O 0
of O 0
ADC O 0
abnormalities O 0
. O 0

However O 0
, O 0
fluid O 0
attenuated O 0
inversion O 0
recovery O 0
( O 0
FLAIR O 0
) O 0
sequences O 0
frequently O 0
revealed O 0
persistent O 0
white B-Disease 0
matter I-Disease 0
abnormalities I-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
Several O 0
pathophysiological O 0
models O 0
of O 0
delayed O 0
leukoencephalopathy B-Disease 0
after O 0
exposure O 0
to O 0
intrathecal O 0
or O 0
systemic O 0
chemotherapy O 0
have O 0
been O 0
proposed O 0
. O 0

DWI O 0
findings O 0
in O 0
this O 0
cohort O 0
are O 0
indicative O 0
of O 0
cytotoxic B-Disease 0
oedema I-Disease 0
within I-Disease 0
cerebral I-Disease 0
white I-Disease 0
matter I-Disease 0
and O 0
lend O 0
support O 0
to O 0
an O 0
at O 0
least O 0
partially O 0
reversible O 0
metabolic O 0
derangement O 0
as O 0
the O 0
basis O 0
for O 0
this O 0
syndrome O 0
. O 0

Prenatal O 0
exposure O 0
to O 0
fluoxetine B-Chemical 0
induces O 0
fetal B-Disease 0
pulmonary I-Disease 0
hypertension I-Disease 0
in O 0
the O 0
rat O 0
. O 0

RATIONALE O 0
: O 0
Fluoxetine B-Chemical 0
is O 0
a O 0
selective O 0
serotonin B-Chemical 0
reuptake O 0
inhibitor O 0
antidepressant O 0
widely O 0
used O 0
by O 0
pregnant O 0
women O 0
. O 0

Epidemiological O 0
data O 0
suggest O 0
that O 0
fluoxetine B-Chemical 0
exposure O 0
prenatally O 0
increases O 0
the O 0
prevalence O 0
of O 0
persistent O 0
pulmonary B-Disease 0
hypertension I-Disease 0
syndrome I-Disease 0
of O 0
the O 0
newborn O 0
. O 0

The O 0
mechanism O 0
responsible O 0
for O 0
this O 0
effect O 0
is O 0
unclear O 0
and O 0
paradoxical O 0
, O 0
considering O 0
the O 0
current O 0
evidence O 0
of O 0
a O 0
pulmonary B-Disease 0
hypertension I-Disease 0
protective O 0
fluoxetine B-Chemical 0
effect O 0
in O 0
adult O 0
rodents O 0
. O 0

OBJECTIVES O 0
: O 0
To O 0
evaluate O 0
the O 0
fluoxetine B-Chemical 0
effect O 0
on O 0
fetal O 0
rat O 0
pulmonary O 0
vascular O 0
smooth O 0
muscle O 0
mechanical O 0
properties O 0
and O 0
cell O 0
proliferation O 0
rate O 0
. O 0

METHODS O 0
: O 0
Pregnant O 0
rats O 0
were O 0
treated O 0
with O 0
fluoxetine B-Chemical 0
( O 0
10 O 0
mg O 0
/ O 0
kg O 0
) O 0
from O 0
Day O 0
11 O 0
through O 0
Day O 0
21 O 0
of O 0
gestation O 0
. O 0

MEASUREMENTS O 0
AND O 0
MAIN O 0
RESULTS O 0
: O 0
Fetuses O 0
were O 0
delivered O 0
by O 0
cesarean O 0
section O 0
. O 0

As O 0
compared O 0
with O 0
controls O 0
, O 0
fluoxetine B-Chemical 0
exposure O 0
resulted O 0
in O 0
fetal B-Disease 0
pulmonary I-Disease 0
hypertension I-Disease 0
as O 0
evidenced O 0
by O 0
an O 0
increase O 0
in O 0
the O 0
weight O 0
ratio O 0
of O 0
the O 0
right O 0
ventricle O 0
to O 0
the O 0
left O 0
ventricle O 0
plus O 0
septum O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
02 O 0
) O 0
and O 0
by O 0
an O 0
increase O 0
in O 0
pulmonary O 0
arterial O 0
medial O 0
thickness O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Postnatal O 0
mortality O 0
was O 0
increased O 0
among O 0
experimental O 0
animals O 0
, O 0
and O 0
arterial O 0
oxygen B-Chemical 0
saturation O 0
was O 0
96 O 0
+ O 0
/ O 0
- O 0
1 O 0
% O 0
in O 0
1 O 0
- O 0
day O 0
- O 0
old O 0
control O 0
animals O 0
and O 0
significantly O 0
lower O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
in O 0
fluoxetine B-Chemical 0
- O 0
exposed O 0
pups O 0
( O 0
79 O 0
+ O 0
/ O 0
- O 0
2 O 0
% O 0
) O 0
. O 0

In O 0
vitro O 0
, O 0
fluoxetine B-Chemical 0
induced O 0
pulmonary O 0
arterial O 0
muscle O 0
contraction O 0
in O 0
fetal O 0
, O 0
but O 0
not O 0
adult O 0
, O 0
animals O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
and O 0
reduced O 0
serotonin B-Chemical 0
- O 0
induced O 0
contraction O 0
at O 0
both O 0
ages O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

After O 0
in O 0
utero O 0
exposure O 0
to O 0
a O 0
low O 0
fluoxetine B-Chemical 0
concentration O 0
the O 0
pulmonary O 0
arterial O 0
smooth O 0
muscle O 0
cell O 0
proliferation O 0
rate O 0
was O 0
significantly O 0
increased O 0
in O 0
fetal O 0
, O 0
but O 0
not O 0
adult O 0
, O 0
cells 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
In O 0
contrast O 0
to O 0
the O 0
adult O 0
, O 0
fluoxetine B-Chemical 0
exposure O 0
in O 0
utero O 0
induces O 0
pulmonary B-Disease 0
hypertension I-Disease 0
in O 0
the O 0
fetal O 0
rat O 0
as O 0
a O 0
result O 0
of O 0
a O 0
developmentally O 0
regulated O 0
increase O 0
in O 0
pulmonary O 0
vascular O 0
smooth O 0
muscle O 0
proliferation O 0
. O 0

Disulfiram B-Chemical 0
- O 0
induced O 0
transient O 0
optic B-Disease 0
and I-Disease 0
peripheral I-Disease 0
neuropathy I-Disease 0
: O 0
a O 0
case O 0
report O 0
. O 0

AIM O 0
: O 0
To O 0
report O 0
a O 0
case O 0
of O 0
optic B-Disease 0
and I-Disease 0
peripheral I-Disease 0
neuropathy I-Disease 0
after O 0
chronic O 0
use O 0
of O 0
disulfiram B-Chemical 0
for O 0
alcohol B-Disease 0
dependence I-Disease 0
management O 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
A O 0
case O 0
report O 0
. O 0

RESULTS O 0
: O 0
A O 0
57 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
presented O 0
with O 0
gradual O 0
loss B-Disease 0
of I-Disease 0
vision I-Disease 0
in O 0
both O 0
eyes O 0
with O 0
intermittent O 0
headaches B-Disease 0
for O 0
2 O 0
months O 0
. O 0

He O 0
also O 0
complained O 0
of O 0
paraesthesia B-Disease 0
with O 0
numbness B-Disease 0
in O 0
both O 0
feet O 0
. O 0

His O 0
vision O 0
was O 0
6 O 0
/ O 0
15 O 0
and O 0
2 O 0
/ O 0
60 O 0
in O 0
the O 0
right O 0
and O 0
left O 0
eyes O 0
, O 0
respectively O 0
. O 0

Fundoscopy O 0
revealed O 0
bilaterally O 0
swollen O 0
optic O 0
nerve O 0
heads O 0
. O 0

Visual O 0
field O 0
testing O 0
confirmed O 0
bilateral O 0
central O 0
- O 0
caecal O 0
scotomata B-Disease 0
. O 0

He O 0
had O 0
been O 0
taking O 0
disulfiram B-Chemical 0
for O 0
alcohol B-Disease 0
dependence I-Disease 0
for O 0
the O 0
preceding O 0
3 O 0
years O 0
. O 0

Disulfiram B-Chemical 0
discontinuation O 0
lead O 0
to O 0
an O 0
immediate O 0
symptomatic O 0
improvement O 0
. O 0

CONCLUSION O 0
: O 0
Physicians O 0
initiating O 0
long O 0
- O 0
term O 0
disulfiram B-Chemical 0
therapy O 0
should O 0
be O 0
aware O 0
of O 0
these O 0
adverse O 0
effects O 0
. O 0

They O 0
should O 0
recommend O 0
annual O 0
ophthalmic O 0
reviews O 0
with O 0
visual O 0
field O 0
testing O 0
. O 0

Patients O 0
should O 0
be O 0
reassured O 0
with O 0
respect O 0
to O 0
the O 0
reversibility O 0
of O 0
these O 0
adverse O 0
effects O 0
. O 0

Intraocular O 0
pressure O 0
in O 0
patients O 0
with O 0
uveitis B-Disease 0
treated O 0
with O 0
fluocinolone B-Chemical 0
acetonide I-Chemical 0
implants O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
report O 0
the O 0
incidence O 0
and O 0
management O 0
of O 0
elevated B-Disease 0
intraocular I-Disease 0
pressure I-Disease 0
( O 0
IOP O 0
) O 0
in O 0
patients O 0
with O 0
uveitis B-Disease 0
treated O 0
with O 0
the O 0
fluocinolone B-Chemical 0
acetonide I-Chemical 0
( O 0
FA B-Chemical 0
) O 0
intravitreal O 0
implant O 0
. O 0

DESIGN O 0
: O 0
Pooled O 0
data O 0
from O 0
3 O 0
multicenter O 0
, O 0
double O 0
- O 0
masked O 0
, O 0
randomized O 0
, O 0
controlled O 0
, O 0
phase O 0
2b O 0
/ O 0
3 O 0
clinical O 0
trials O 0
evaluating O 0
the O 0
safety O 0
and O 0
efficacy O 0
of O 0
the O 0
0 O 0
. O 0
59 O 0
- O 0
mg O 0
or O 0
2 O 0
. O 0
1 O 0
- O 0
mg O 0
FA B-Chemical 0
intravitreal O 0
implant O 0
or O 0
standard O 0
therapy O 0
were O 0
analyzed O 0
. O 0

RESULTS O 0
: O 0
During O 0
the O 0
3 O 0
- O 0
year O 0
follow O 0
- O 0
up O 0
, O 0
71 O 0
. O 0
0 O 0
% O 0
of O 0
implanted O 0
eyes O 0
had O 0
an O 0
IOP O 0
increase O 0
of O 0
10 O 0
mm O 0
Hg O 0
or O 0
more O 0
than O 0
baseline O 0
and O 0
55 O 0
. O 0
1 O 0
% O 0
, O 0
24 O 0
. O 0
7 O 0
% O 0
, O 0
and O 0
6 O 0
. O 0
2 O 0
% O 0
of O 0
eyes O 0
reached O 0
an O 0
IOP O 0
of O 0
30 O 0
mm O 0
Hg O 0
or O 0
more O 0
, O 0
40 O 0
mm O 0
Hg O 0
or O 0
more O 0
, O 0
and O 0
50 O 0
mm O 0
Hg O 0
or O 0
more O 0
, O 0
respectively O 0
. O 0

Topical O 0
IOP O 0
- O 0
lowering O 0
medication O 0
was O 0
administered O 0
in O 0
74 O 0
. O 0
8 O 0
% O 0
of O 0
implanted O 0
eyes O 0
, O 0
and O 0
IOP O 0
- O 0
lowering O 0
surgeries O 0
, O 0
most O 0
of O 0
which O 0
were O 0
trabeculectomies O 0
( O 0
76 O 0
. O 0
2 O 0
% O 0
) O 0
, O 0
were O 0
performed O 0
on O 0
36 O 0
. O 0
6 O 0
% O 0
of O 0
implanted O 0
eyes O 0
. O 0

Intraocular O 0
pressure O 0
- O 0
lowering O 0
surgeries O 0
were O 0
considered O 0
a O 0
success O 0
( O 0
postoperative O 0
IOP O 0
of O 0
6 O 0
- O 0
21 O 0
mm O 0
Hg O 0
with O 0
or O 0
without O 0
additional O 0
IOP O 0
- O 0
lowering O 0
medication O 0
) O 0
in O 0
85 O 0
. O 0
1 O 0
% O 0
of O 0
eyes O 0
at O 0
1 O 0
year O 0
. O 0

The O 0
rate O 0
of O 0
hypotony B-Disease 0
( O 0
IOP O 0
< O 0
/ O 0
= O 0
5 O 0
mm O 0
Hg O 0
) O 0
following O 0
IOP O 0
- O 0
lowering O 0
surgery O 0
( O 0
42 O 0
. O 0
5 O 0
% O 0
) O 0
was O 0
not O 0
different O 0
from O 0
that O 0
of O 0
implanted O 0
eyes O 0
not O 0
subjected O 0
to O 0
surgery O 0
( O 0
35 O 0
. O 0
4 O 0
% O 0
) O 0
( O 0
P O 0
= O 0
. O 0
09 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
Elevated O 0
IOP O 0
is O 0
a O 0
significant O 0
complication O 0
with O 0
the O 0
FA O 0
intravitreal O 0
implant O 0
but O 0
may O 0
be O 0
controlled O 0
with O 0
medication O 0
and O 0
surgery O 0
. O 0

Myocardial O 0
Fas O 0
ligand O 0
expression O 0
increases O 0
susceptibility O 0
to O 0
AZT B-Chemical 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
. O 0

BACKGROUND O 0
: O 0
Dilated B-Disease 0
cardiomyopathy I-Disease 0
( O 0
DCM B-Disease 0
) O 0
and O 0
myocarditis B-Disease 0
occur O 0
in O 0
many O 0
HIV B-Disease 0
- I-Disease 0
infected I-Disease 0
individuals O 0
, O 0
resulting O 0
in O 0
symptomatic O 0
heart B-Disease 0
failure I-Disease 0
in O 0
up O 0
to O 0
5 O 0
% O 0
of O 0
patients O 0
. O 0

Highly O 0
active O 0
antiretroviral O 0
therapy O 0
( O 0
HAART O 0
) O 0
has O 0
significantly O 0
reduced O 0
morbidity O 0
and O 0
mortality O 0
of O 0
acquired B-Disease 0
immunodeficiency I-Disease 0
syndrome I-Disease 0
( O 0
AIDS B-Disease 0
) O 0
, O 0
but O 0
has O 0
resulted O 0
in O 0
an O 0
increase O 0
in O 0
cardiac B-Disease 0
and I-Disease 0
skeletal I-Disease 0
myopathies I-Disease 0
. O 0

METHODS O 0
AND O 0
RESULTS O 0
: O 0
In O 0
order O 0
to O 0
investigate O 0
whether O 0
the O 0
HAART O 0
component O 0
zidovudine B-Chemical 0
( O 0
3 B-Chemical 0
' I-Chemical 0
- I-Chemical 0
azido I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
' I-Chemical 0
, I-Chemical 0
3 I-Chemical 0
' I-Chemical 0
- I-Chemical 0
deoxythymidine I-Chemical 0
; O 0
AZT B-Chemical 0
) O 0
triggers O 0
the O 0
Fas O 0
- O 0
dependent O 0
cell O 0
- O 0
death O 0
pathway O 0
and O 0
cause O 0
cytoskeletal O 0
disruption O 0
in O 0
a O 0
murine O 0
model O 0
of O 0
DCM B-Disease 0
, O 0
8 O 0
- O 0
week O 0
- O 0
old O 0
transgenic O 0
( O 0
expressing O 0
Fas O 0
ligand O 0
in O 0
the O 0
myocardium O 0
: O 0
FasL O 0
Tg O 0
) O 0
and O 0
non O 0
- O 0
transgenic O 0
( O 0
NTg O 0
) O 0
mice O 0
received O 0
water O 0
ad O 0
libitum O 0
containing O 0
different O 0
concentrations O 0
of O 0
AZT B-Chemical 0
( O 0
0 O 0
, O 0
0 O 0
. O 0
07 O 0
, O 0
0 O 0
. O 0
2 O 0
, O 0
and O 0
0 O 0
. O 0
7 O 0
mg O 0
/ O 0
ml O 0
) O 0
. O 0

After O 0
6 O 0
weeks O 0
, O 0
cardiac O 0
function O 0
was O 0
assessed O 0
by O 0
echocardiography O 0
and O 0
morphology O 0
was O 0
assessed O 0
by O 0
histopathologic O 0
and O 0
immunohistochemical O 0
methods O 0
. O 0

NTg O 0
and O 0
untreated O 0
FasL O 0
Tg O 0
mice O 0
showed O 0
little O 0
or O 0
no O 0
change O 0
in O 0
cardiac O 0
structure O 0
or O 0
function O 0
. O 0

In O 0
contrast O 0
, O 0
AZT B-Chemical 0
- O 0
treated O 0
FasL O 0
Tg O 0
mice O 0
developed O 0
cardiac B-Disease 0
dilation I-Disease 0
and O 0
depressed O 0
cardiac O 0
function O 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
manner O 0
, O 0
with O 0
concomitant O 0
inflammatory O 0
infiltration O 0
of O 0
both O 0
ventricles O 0
. O 0

These O 0
changes O 0
were O 0
associated O 0
with O 0
an O 0
increased O 0
sarcolemmal O 0
expression O 0
of O 0
Fas O 0
and O 0
FasL O 0
, O 0
as O 0
well O 0
as O 0
increased O 0
activation O 0
of O 0
caspase O 0
3 O 0
, O 0
translocation O 0
of O 0
calpain O 0
1 O 0
to O 0
the O 0
sarcolemma O 0
and O 0
sarcomere O 0
, O 0
and O 0
increased O 0
numbers O 0
of O 0
cells O 0
undergoing O 0
apoptosis O 0
. O 0

These O 0
were O 0
associated O 0
with O 0
changes O 0
in O 0
dystrophin O 0
and O 0
cardiac O 0
troponin O 0
I O 0
localization O 0
, O 0
as O 0
well O 0
as O 0
loss O 0
of O 0
sarcolemmal O 0
integrity O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
expression O 0
of O 0
Fas O 0
ligand O 0
in O 0
the O 0
myocardium O 0
, O 0
as O 0
identified O 0
in O 0
HIV O 0
- O 0
positive O 0
patients O 0
, O 0
might O 0
increase O 0
the O 0
susceptibility O 0
to O 0
HAART O 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
due O 0
to O 0
activation O 0
of O 0
apoptotic O 0
pathways O 0
, O 0
resulting O 0
in O 0
cardiac B-Disease 0
dilation I-Disease 0
and I-Disease 0
dysfunction I-Disease 0
. O 0

Gastrointestinal O 0
tolerability O 0
of O 0
etoricoxib B-Chemical 0
in O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
patients O 0
: O 0
results O 0
of O 0
the O 0
etoricoxib B-Chemical 0
vs O 0
diclofenac B-Chemical 0
sodium I-Chemical 0
gastrointestinal O 0
tolerability O 0
and O 0
effectiveness O 0
trial O 0
( O 0
EDGE O 0
- O 0
II O 0
) O 0
. O 0

OBJECTIVE O 0
: O 0
A O 0
randomised O 0
, O 0
double O 0
- O 0
blind O 0
study O 0
to O 0
compare O 0
the O 0
gastrointestinal O 0
( O 0
GI O 0
) O 0
tolerability O 0
, O 0
safety O 0
and O 0
efficacy O 0
of O 0
etoricoxib B-Chemical 0
and O 0
diclofenac B-Chemical 0
in O 0
patients O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
( O 0
RA B-Disease 0
) O 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
A O 0
total O 0
of O 0
4086 O 0
patients O 0
( O 0
mean O 0
age O 0
60 O 0
. O 0
8 O 0
years O 0
) O 0
diagnosed O 0
with O 0
RA B-Disease 0
were O 0
enrolled O 0
and O 0
received O 0
etoricoxib B-Chemical 0
90 O 0
mg O 0
daily O 0
( O 0
n O 0
= O 0
2032 O 0
) O 0
or O 0
diclofenac B-Chemical 0
75 O 0
mg O 0
twice O 0
daily O 0
( O 0
n O 0
= O 0
2054 O 0
) O 0
. O 0

Use O 0
of O 0
gastroprotective O 0
agents O 0
and O 0
low O 0
- O 0
dose O 0
aspirin B-Chemical 0
was O 0
allowed O 0
. O 0

The O 0
prespecified O 0
primary O 0
end O 0
point O 0
consisted O 0
of O 0
the O 0
cumulative O 0
rate O 0
of O 0
patient O 0
discontinuations O 0
due O 0
to O 0
clinical O 0
and O 0
laboratory O 0
GI O 0
adverse O 0
experiences O 0
( O 0
AEs O 0
) O 0
. O 0

General O 0
safety O 0
was O 0
also O 0
assessed O 0
, O 0
including O 0
adjudicated O 0
thrombotic B-Disease 0
cardiovascular I-Disease 0
event O 0
data O 0
. O 0

Efficacy O 0
was O 0
evaluated O 0
using O 0
the O 0
Patient O 0
Global O 0
Assessment O 0
of O 0
Disease O 0
Status O 0
( O 0
PGADS O 0
; O 0
0 O 0
- O 0
4 O 0
point O 0
scale O 0
) O 0
. O 0

RESULTS O 0
: O 0
Mean O 0
( O 0
SD O 0
; O 0
maximum O 0
) O 0
duration O 0
of O 0
treatment O 0
was O 0
19 O 0
. O 0
3 O 0
( O 0
10 O 0
. O 0
3 O 0
; O 0
32 O 0
. O 0
9 O 0
) O 0
and O 0
19 O 0
. O 0
1 O 0
( O 0
10 O 0
. O 0
4 O 0
; O 0
33 O 0
. O 0
1 O 0
) O 0
months O 0
in O 0
the O 0
etoricoxib B-Chemical 0
and O 0
diclofenac B-Chemical 0
groups O 0
, O 0
respectively O 0
. O 0

The O 0
cumulative O 0
discontinuation O 0
rate O 0
due O 0
to O 0
GI B-Disease 0
AEs I-Disease 0
was O 0
significantly O 0
lower O 0
with O 0
etoricoxib B-Chemical 0
than O 0
diclofenac B-Chemical 0
( O 0
5 O 0
. O 0
2 O 0
vs O 0
8 O 0
. O 0
5 O 0
events O 0
per O 0
100 O 0
patient O 0
- O 0
years O 0
, O 0
respectively O 0
; O 0
hazard O 0
ratio O 0
0 O 0
. O 0
62 O 0
( O 0
95 O 0
% O 0
CI O 0
: O 0
0 O 0
. O 0
47 O 0
, O 0
0 O 0
. O 0
81 O 0
; O 0
p O 0
< O 0
or O 0
= O 0
0 O 0
. O 0
001 O 0
) O 0
) O 0
. O 0

The O 0
incidence O 0
of O 0
discontinuations O 0
for O 0
hypertension B-Disease 0
- O 0
related O 0
and O 0
oedema B-Disease 0
- O 0
related O 0
AEs O 0
were O 0
significantly O 0
higher O 0
with O 0
etoricoxib B-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
% O 0
and O 0
1 O 0
. O 0
1 O 0
% O 0
respectively O 0
) O 0
compared O 0
with O 0
diclofenac B-Chemical 0
( O 0
1 O 0
. O 0
5 O 0
% O 0
and O 0
0 O 0
. O 0
4 O 0
% O 0
respectively O 0
; O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
for O 0
hypertension B-Disease 0
and O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
for O 0
oedema B-Disease 0
) O 0
. O 0

Etoricoxib B-Chemical 0
and O 0
diclofenac B-Chemical 0
treatment O 0
resulted O 0
in O 0
similar O 0
efficacy O 0
( O 0
PGADS O 0
mean O 0
changes O 0
from O 0
baseline O 0
- O 0
0 O 0
. O 0
62 O 0
vs O 0
- O 0
0 O 0
. O 0
58 O 0
, O 0
respectively O 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
Etoricoxib B-Chemical 0
90 O 0
mg O 0
demonstrated O 0
a O 0
significantly O 0
lower O 0
risk O 0
for O 0
discontinuing O 0
treatment O 0
due O 0
to O 0
GI B-Disease 0
AEs I-Disease 0
compared O 0
with O 0
diclofenac B-Chemical 0
150 O 0
mg O 0
. O 0

Discontinuations O 0
from O 0
renovascular O 0
AEs O 0
, O 0
although O 0
less O 0
common O 0
than O 0
discontinuations O 0
from O 0
GI B-Disease 0
AEs I-Disease 0
, O 0
were O 0
significantly O 0
higher O 0
with O 0
etoricoxib B-Chemical 0
. O 0

Anxiogenic O 0
potential O 0
of O 0
ciprofloxacin B-Chemical 0
and O 0
norfloxacin B-Chemical 0
in O 0
rats O 0
. O 0

INTRODUCTION O 0
: O 0
The O 0
possible O 0
anxiogenic O 0
effects O 0
of O 0
fluoroquinolones B-Chemical 0
, O 0
namely O 0
ciprofloxacin B-Chemical 0
and O 0
norfloxacin B-Chemical 0
, O 0
were O 0
investigated O 0
in O 0
adult O 0
Charles O 0
Foster O 0
albino O 0
rats O 0
of O 0
either O 0
sex O 0
, O 0
weighing O 0
150 O 0
- O 0
200 O 0
g O 0
. O 0

METHODS O 0
: O 0
The O 0
drugs O 0
were O 0
given O 0
orally O 0
, O 0
in O 0
doses O 0
of O 0
50 O 0
mg O 0
/ O 0
kg O 0
for O 0
five O 0
consecutive O 0
days O 0
and O 0
the O 0
experiments O 0
were O 0
performed O 0
on O 0
the O 0
fifth O 0
day O 0
. O 0

The O 0
tests O 0
included O 0
open O 0
- O 0
field O 0
exploratory O 0
behaviour O 0
, O 0
elevated O 0
plus O 0
maze O 0
and O 0
elevated O 0
zero O 0
maze O 0
, O 0
social O 0
interaction O 0
and O 0
novelty O 0
- O 0
suppressed O 0
feeding O 0
latency O 0
behaviour O 0
. O 0

RESULTS O 0
: O 0
The O 0
results O 0
indicate O 0
that O 0
ciprofloxacin B-Chemical 0
- O 0
and O 0
norfloxacin B-Chemical 0
- O 0
treated O 0
rats O 0
showed O 0
anxious B-Disease 0
behaviour I-Disease 0
in O 0
comparison O 0
to O 0
control O 0
rats O 0
in O 0
all O 0
the O 0
parameters O 0
studied O 0
. O 0

However O 0
, O 0
ciprofloxacin B-Chemical 0
- O 0
and O 0
norfloxacin B-Chemical 0
- O 0
treated O 0
rats O 0
did O 0
not O 0
differ O 0
significantly O 0
from O 0
each O 0
other O 0
in O 0
various O 0
behavioural O 0
parameters O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
present O 0
experimental O 0
findings O 0
substantiate O 0
the O 0
clinically O 0
observed O 0
anxiogenic O 0
potential O 0
of O 0
ciprofloxacin B-Chemical 0
and O 0
norfloxacin B-Chemical 0
. O 0

Reduction O 0
of O 0
pain B-Disease 0
during O 0
induction O 0
with O 0
target O 0
- O 0
controlled O 0
propofol B-Chemical 0
and O 0
remifentanil B-Chemical 0
. O 0

BACKGROUND O 0
: O 0
Pain B-Disease 0
on O 0
injection O 0
of O 0
propofol B-Chemical 0
is O 0
unpleasant O 0
. O 0

We O 0
hypothesized O 0
that O 0
propofol B-Chemical 0
infusion O 0
pain B-Disease 0
might O 0
be O 0
prevented O 0
by O 0
infusing O 0
remifentanil B-Chemical 0
before O 0
starting O 0
the O 0
propofol B-Chemical 0
infusion O 0
in O 0
a O 0
clinical O 0
setting O 0
where O 0
target O 0
- O 0
controlled O 0
infusions O 0
( O 0
TCI O 0
) O 0
of O 0
both O 0
drugs O 0
were O 0
used O 0
. 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
trial O 0
was O 0
performed O 0
to O 0
determine O 0
the O 0
effect O 0
- O 0
site O 0
concentration O 0
( O 0
Ce O 0
) O 0
of O 0
remifentanil B-Chemical 0
to O 0
prevent O 0
the O 0
pain B-Disease 0
without O 0
producing O 0
complications O 0
. O 0

METHODS O 0
: O 0
A O 0
total O 0
of O 0
128 O 0
patients O 0
undergoing O 0
general O 0
surgery O 0
were O 0
randomly O 0
allocated O 0
to O 0
receive O 0
normal O 0
saline O 0
( O 0
control O 0
) O 0
or O 0
remifentanil B-Chemical 0
to O 0
a O 0
target O 0
Ce O 0
of O 0
2 O 0
ng O 0
ml O 0
( O 0
- O 0
1 O 0
) O 0
( O 0
R2 O 0
) O 0
, O 0
4 O 0
ng O 0
ml O 0
( O 0
- O 0
1 O 0
) O 0
( O 0
R4 O 0
) O 0
, O 0
or O 0
6 O 0
ng O 0
ml O 0
( O 0
- O 0
1 O 0
) O 0
( O 0
R6 O 0
) O 0
administered O 0
via O 0
TCI O 0
. O 0

After O 0
the O 0
target O 0
Ce O 0
was O 0
achieved O 0
, O 0
the O 0
infusion O 0
of O 0
propofol B-Chemical 0
was O 0
started O 0
. O 0

Remifentanil B-Chemical 0
- O 0
related O 0
complications O 0
were O 0
assessed O 0
during O 0
the O 0
remifentanil B-Chemical 0
infusion O 0
, O 0
and O 0
pain B-Disease 0
caused O 0
by O 0
propofol B-Chemical 0
was O 0
evaluated O 0
using O 0
a O 0
four O 0
- O 0
point O 0
scale O 0
during O 0
the O 0
propofol B-Chemical 0
infusion O 0
. O 0

RESULTS O 0
: O 0
The O 0
incidence O 0
of O 0
pain B-Disease 0
was O 0
significantly O 0
lower O 0
in O 0
Groups O 0
R4 O 0
and O 0
R6 O 0
than O 0
in O 0
the O 0
control O 0
and O 0
R2 O 0
groups O 0
( O 0
12 O 0
/ O 0
32 O 0
and O 0
6 O 0
/ O 0
31 O 0
vs O 0
26 O 0
/ O 0
31 O 0
and O 0
25 O 0
/ O 0
32 O 0
, O 0
respectively O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Pain B-Disease 0
was O 0
less O 0
severe O 0
in O 0
Groups O 0
R4 O 0
and O 0
R6 O 0
than O 0
in O 0
the O 0
control O 0
and O 0
R2 O 0
groups O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

However O 0
, O 0
both O 0
incidence O 0
and O 0
severity O 0
of O 0
pain B-Disease 0
were O 0
not O 0
different O 0
between O 0
Groups O 0
R4 O 0
and O 0
R6 O 0
. O 0

No O 0
significant O 0
complications O 0
were O 0
observed O 0
during O 0
the O 0
study O 0
. O 0

CONCLUSIONS O 0
: O 0
During O 0
induction O 0
of O 0
anaesthesia O 0
with O 0
TCI O 0
of O 0
propofol B-Chemical 0
and O 0
remifentanil B-Chemical 0
, O 0
a O 0
significant O 0
reduction O 0
in O 0
propofol B-Chemical 0
infusion O 0
pain B-Disease 0
was O 0
achieved O 0
without O 0
significant O 0
complications O 0
by O 0
prior O 0
administration O 0
of O 0
remifentanil B-Chemical 0
at O 0
a O 0
target O 0
Ce O 0
of O 0
4 O 0
ng O 0
ml O 0
( O 0
- O 0
1 O 0
) O 0
. O 0

Dexmedetomidine B-Chemical 0
and O 0
cardiac O 0
protection O 0
for O 0
non O 0
- O 0
cardiac O 0
surgery O 0
: O 0
a O 0
meta O 0
- O 0
analysis O 0
of O 0
randomised O 0
controlled O 0
trials O 0
. O 0

We O 0
conducted O 0
a O 0
systematic O 0
review O 0
of O 0
the O 0
effects O 0
of O 0
dexmedetomidine B-Chemical 0
on O 0
cardiac O 0
outcomes O 0
following O 0
non O 0
- O 0
cardiac O 0
surgery O 0
. O 0

We O 0
included O 0
prospective O 0
, O 0
randomised O 0
peri O 0
- O 0
operative O 0
studies O 0
of O 0
dexmedetomidine B-Chemical 0
that O 0
reported O 0
mortality O 0
, O 0
cardiac O 0
morbidity O 0
or O 0
adverse O 0
drug O 0
events O 0
. O 0

A O 0
PubMed O 0
Central O 0
and O 0
EMBASE O 0
search O 0
was O 0
conducted O 0
up O 0
to O 0
July O 0
2007 O 0
. O 0

The O 0
reference O 0
lists O 0
of O 0
identified O 0
papers O 0
were O 0
examined O 0
for O 0
further O 0
trials O 0
. O 0

Of O 0
425 O 0
studies O 0
identified O 0
, O 0
20 O 0
were O 0
included O 0
in O 0
the O 0
meta O 0
- O 0
analysis O 0
( O 0
840 O 0
patients O 0
) O 0
. O 0

Dexmedetomidine B-Chemical 0
was O 0
associated O 0
with O 0
a O 0
trend O 0
towards O 0
improved O 0
cardiac O 0
outcomes O 0
; O 0
all O 0
- O 0
cause O 0
mortality O 0
( O 0
OR O 0
0 O 0
. O 0
27 O 0
, O 0
95 O 0
% O 0
CI O 0
0 O 0
. O 0
01 O 0
- O 0
7 O 0
. O 0
13 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
44 O 0
) O 0
, O 0
non O 0
- O 0
fatal O 0
myocardial B-Disease 0
infarction I-Disease 0
( O 0
OR O 0
0 O 0
. O 0
26 O 0
, O 0
95 O 0
% O 0
CI O 0
0 O 0
. O 0
04 O 0
- O 0
1 O 0
. O 0
60 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
14 O 0
) O 0
, O 0
and O 0
myocardial B-Disease 0
ischaemia I-Disease 0
( O 0
OR O 0
0 O 0
. O 0
65 O 0
, O 0
95 O 0
% O 0
CI O 0
0 O 0
. O 0
26 O 0
- O 0
1 O 0
. O 0
63 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
36 O 0
) O 0
. O 0

Peri O 0
- O 0
operative O 0
hypotension B-Disease 0
( O 0
26 O 0
% O 0
, O 0
OR O 0
3 O 0
. O 0
80 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
91 O 0
- O 0
7 O 0
. O 0
54 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
0001 O 0
) O 0
and O 0
bradycardia B-Disease 0
( O 0
17 O 0
% O 0
, O 0
OR O 0
5 O 0
. O 0
45 O 0
, O 0
95 O 0
% O 0
CI O 0
2 O 0
. O 0
98 O 0
- O 0
9 O 0
. O 0
95 O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
00001 O 0
) O 0
were O 0
significantly O 0
increased O 0
. O 0

An O 0
anticholinergic O 0
did O 0
not O 0
reduce O 0
the O 0
incidence O 0
of O 0
bradycardia B-Disease 0
( O 0
p O 0
= O 0
0 O 0
. O 0
43 O 0
) O 0
. O 0

A O 0
randomised O 0
placebo O 0
- O 0
controlled O 0
trial O 0
of O 0
dexmedetomidine B-Chemical 0
is O 0
warranted O 0
. O 0

Myocardial B-Disease 0
infarction I-Disease 0
in O 0
pregnancy O 0
associated O 0
with O 0
clomiphene B-Chemical 0
citrate I-Chemical 0
for O 0
ovulation O 0
induction O 0
: O 0
a O 0
case O 0
report O 0
. O 0

BACKGROUND O 0
: O 0
Clomiphene B-Chemical 0
citrate I-Chemical 0
( O 0
CC B-Chemical 0
) O 0
is O 0
commonly O 0
prescribed O 0
for O 0
ovulation O 0
induction O 0
. O 0

It O 0
is O 0
considered O 0
safe O 0
, O 0
with O 0
minimal O 0
side O 0
effects O 0
. O 0

Thromboembolism B-Disease 0
is O 0
a O 0
rare O 0
but O 0
life O 0
- O 0
threatening O 0
complication O 0
that O 0
has O 0
been O 0
reported O 0
after O 0
ovulation O 0
induction O 0
with O 0
CC B-Chemical 0
. O 0

Spontaneous O 0
coronary B-Disease 0
thrombosis I-Disease 0
or O 0
thromboembolism B-Disease 0
with O 0
subsequent O 0
clot O 0
lysis O 0
has O 0
been O 0
suggested O 0
as O 0
one O 0
of O 0
the O 0
most O 0
common O 0
causes O 0
of O 0
myocardial B-Disease 0
infarction I-Disease 0
( O 0
MI B-Disease 0
) O 0
during O 0
pregnancy O 0
, O 0
with O 0
a O 0
subsequently O 0
normal O 0
coronary O 0
angiogram O 0
. O 0

CASE O 0
: O 0
A O 0
33 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
a O 0
5 O 0
- O 0
week O 0
gestation O 0
had O 0
recently O 0
received O 0
CC B-Chemical 0
for O 0
ovulation O 0
induction O 0
and O 0
presented O 0
with O 0
chest B-Disease 0
pain I-Disease 0
. O 0

An O 0
electrocardiogram O 0
showed O 0
a O 0
lateral O 0
and O 0
anterior O 0
wall O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

Cardiac O 0
enzymes O 0
showed O 0
a O 0
peak O 0
rise O 0
in O 0
troponin O 0
I O 0
to O 0
9 O 0
. O 0
10 O 0
ng O 0
/ O 0
mL O 0
. O 0

An O 0
initial O 0
exercise O 0
stress O 0
test O 0
was O 0
normal O 0
. O 0

At O 0
the O 0
time O 0
of O 0
admission O 0
, O 0
the O 0
patient O 0
was O 0
at O 0
high O 0
risk O 0
of O 0
radiation B-Disease 0
injury I-Disease 0
to O 0
the O 0
fetus O 0
, O 0
so O 0
a O 0
coronary O 0
angiogram O 0
was O 0
postponed O 0
until O 0
the O 0
second O 0
trimester O 0
. O 0

It O 0
showed O 0
normal O 0
coronary O 0
vessels O 0
. O 0

CONCLUSION O 0
: O 0
This O 0
appears O 0
to O 0
be O 0
the O 0
first O 0
reported O 0
case O 0
documenting O 0
a O 0
possible O 0
association O 0
between O 0
CC B-Chemical 0
and O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

Thrombosis B-Disease 0
might O 0
be O 0
a O 0
rare O 0
but O 0
hazardous O 0
complication O 0
of O 0
CC B-Chemical 0
. O 0

Given O 0
this O 0
life O 0
- O 0
threatening O 0
complication O 0
, O 0
appropriate O 0
prophylactic O 0
measures O 0
should O 0
be O 0
used O 0
in O 0
high O 0
- O 0
risk O 0
woman O 0
undergoing O 0
ovarian O 0
stimulation O 0
. O 0

Reverse O 0
or O 0
inverted O 0
left B-Disease 0
ventricular I-Disease 0
apical I-Disease 0
ballooning I-Disease 0
syndrome I-Disease 0
( O 0
reverse O 0
Takotsubo B-Disease 0
cardiomyopathy I-Disease 0
) O 0
in O 0
a O 0
young O 0
woman O 0
in O 0
the O 0
setting O 0
of O 0
amphetamine B-Chemical 0
use O 0
. O 0

Transient O 0
left B-Disease 0
ventricular I-Disease 0
apical I-Disease 0
ballooning I-Disease 0
syndrome I-Disease 0
was O 0
first O 0
described O 0
in O 0
Japan O 0
as O 0
" O 0
Takotsubo B-Disease 0
cardiomyopathy I-Disease 0
. O 0
" O 0
This O 0
syndrome O 0
has O 0
been O 0
identified O 0
in O 0
many O 0
other O 0
countries O 0
. O 0

Many O 0
variations O 0
of O 0
this O 0
syndrome O 0
have O 0
been O 0
recently O 0
described O 0
in O 0
the O 0
literature O 0
. O 0

One O 0
of O 0
the O 0
rarest O 0
is O 0
the O 0
reverse O 0
type O 0
of O 0
this O 0
syndrome O 0
, O 0
with O 0
hyperdynamic O 0
apex O 0
and O 0
complete O 0
akinesia B-Disease 0
of O 0
the O 0
base O 0
( O 0
as O 0
opposed O 0
to O 0
the O 0
classic O 0
apical B-Disease 0
ballooning I-Disease 0
) O 0
. O 0

In O 0
this O 0
article O 0
, O 0
we O 0
report O 0
an O 0
interesting O 0
case O 0
of O 0
a O 0
young O 0
woman O 0
who O 0
presented O 0
with O 0
this O 0
rare O 0
type O 0
of O 0
reverse O 0
apical B-Disease 0
ballooning I-Disease 0
syndrome I-Disease 0
occurring O 0
after O 0
amphetamine B-Chemical 0
use O 0
. O 0

This O 0
report O 0
is O 0
followed O 0
by O 0
review O 0
of O 0
the O 0
literature O 0
. O 0

Results O 0
of O 0
a O 0
comparative O 0
, O 0
phase O 0
III O 0
, O 0
12 O 0
- O 0
week O 0
, O 0
multicenter O 0
, O 0
prospective O 0
, O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
assessment O 0
of O 0
the O 0
efficacy O 0
and O 0
tolerability O 0
of O 0
a O 0
fixed O 0
- O 0
dose O 0
combination O 0
of O 0
telmisartan B-Chemical 0
and O 0
amlodipine B-Chemical 0
versus O 0
amlodipine B-Chemical 0
monotherapy O 0
in O 0
Indian O 0
adults O 0
with O 0
stage O 0
II O 0
hypertension B-Disease 0
. O 0

OBJECTIVE 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
the O 0
efficacy O 0
and O 0
tolerability O 0
of O 0
a O 0
new O 0
fixed O 0
- O 0
dose O 0
combination O 0
( O 0
FDC O 0
) O 0
of O 0
telmisartan B-Chemical 0
40 O 0
mg O 0
+ O 0
amlodipine B-Chemical 0
5 O 0
mg O 0
( O 0
T O 0
+ O 0
A O 0
) O 0
compared O 0
with O 0
amlodipine B-Chemical 0
5 O 0
- O 0
mg O 0
monotherapy O 0
( O 0
A O 0
) O 0
in O 0
adult O 0
Indian O 0
patients O 0
with O 0
stage O 0
II O 0
hypertension B-Disease 0
. O 0

METHODS O 0
: O 0
This O 0
comparative O 0
, O 0
Phase O 0
III O 0
, O 0
12 O 0
- O 0
week O 0
, O 0
multicenter O 0
, O 0
prospective O 0
, O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
study O 0
was O 0
conducted O 0
in O 0
Indian O 0
patients O 0
aged O 0
18 O 0
to O 0
65 O 0
years O 0
with O 0
established O 0
stage O 0
II O 0
hypertension B-Disease 0
. O 0

Patients O 0
were O 0
treated O 0
with O 0
oral O 0
FDC O 0
of O 0
T O 0
+ O 0
A O 0
or O 0
A O 0
QD O 0
before O 0
breakfast O 0
for O 0
12 O 0
weeks O 0
; O 0
blood O 0
pressure O 0
( O 0
BP O 0
) O 0
and O 0
heart O 0
rate O 0
were O 0
measured O 0
in O 0
the O 0
sitting O 0
position O 0
. O 0

Primary O 0
efficacy O 0
end O 0
points O 0
were O 0
reduction O 0
in O 0
clinical O 0
systolic O 0
BP O 0
( O 0
SBP O 0
) O 0
/ O 0
diastolic O 0
BP O 0
( O 0
DBP O 0
) O 0
from O 0
baseline O 0
to O 0
study O 0
end O 0
and O 0
number O 0
of O 0
responders O 0
( O 0
ie O 0
, O 0
patients O 0
who O 0
achieved O 0
target O 0
SBP O 0
/ O 0
DBP O 0
< O 0
130 O 0
/ O 0
< O 0
80 O 0
mm O 0
Hg O 0
) O 0
at O 0
end O 0
of O 0
study O 0
. O 0

Tolerability O 0
was O 0
assessed O 0
by O 0
treatment O 0
- O 0
emergent O 0
adverse O 0
events O 0
, O 0
identified O 0
using O 0
physical O 0
examination O 0
, O 0
laboratory O 0
analysis O 0
, O 0
and O 0
electrocardiography O 0
. O 0

RESULTS O 0
: O 0
A O 0
total O 0
of O 0
210 O 0
patients O 0
were O 0
enrolled O 0
in O 0
the O 0
study O 0
; O 0
203 O 0
patients O 0
( O 0
143 O 0
men O 0
, O 0
60 O 0
women O 0
) O 0
completed O 0
the O 0
study O 0
while O 0
7 O 0
were O 0
lost O 0
to O 0
follow O 0
- O 0
up O 0
( O 0
4 O 0
patients O 0
in O 0
the O 0
T O 0
+ O 0
A O 0
group O 0
and O 0
3 O 0
in O 0
the O 0
A O 0
group O 0
) O 0
and O 0
considered O 0
with O 0
- O 0
drawn O 0
. O 0

At O 0
study O 0
end O 0
, O 0
statistically O 0
significant O 0
percentage O 0
reductions O 0
from O 0
baseline O 0
within O 0
groups O 0
and O 0
between O 0
groups O 0
were O 0
observed O 0
in O 0
SBP O 0
( O 0
T O 0
+ O 0
A O 0
[ O 0
- O 0
27 O 0
. O 0
4 O 0
% O 0
] O 0
; O 0
A O 0
[ O 0
- O 0
16 O 0
. O 0
6 O 0
% O 0
] O 0
) O 0
and O 0
DBP O 0
( O 0
T O 0
+ O 0
A O 0
[ O 0
- O 0
20 O 0
. O 0
1 O 0
% O 0
] O 0
; O 0
A O 0
[ O 0
- O 0
13 O 0
. O 0
3 O 0
% O 0
] O 0
) O 0
( O 0
all O 0
, O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Response O 0
rates O 0
were O 0
87 O 0
. O 0
3 O 0
% O 0
( O 0
89 O 0
/ O 0
102 O 0
) O 0
in O 0
the O 0
T O 0
+ O 0
A O 0
group O 0
and O 0
69 O 0
. O 0
3 O 0
% O 0
( O 0
70 O 0
/ O 0
101 O 0
) O 0
in O 0
the O 0
A O 0
group O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

The O 0
prevalences O 0
of O 0
adverse O 0
events O 0
were O 0
not O 0
significantly O 0
different O 0
between O 0
the O 0
2 O 0
treatment O 0
groups O 0
( O 0
T O 0
+ O 0
A O 0
, O 0
16 O 0
. O 0
0 O 0
% O 0
[ O 0
17 O 0
/ O 0
106 O 0
] O 0
; O 0
A O 0
, O 0
15 O 0
. O 0
4 O 0
% O 0
[ O 0
16 O 0
/ O 0
104 O 0
] O 0
) O 0
. O 0

Peripheral O 0
edema B-Disease 0
was O 0
reported O 0
in O 0
8 O 0
. O 0
5 O 0
% O 0
patients O 0
( O 0
9 O 0
/ O 0
106 O 0
) O 0
in O 0
the O 0
T O 0
+ O 0
A O 0
group O 0
compared O 0
with O 0
13 O 0
. O 0
5 O 0
% O 0
( O 0
14 O 0
/ O 0
104 O 0
) O 0
in O 0
the O 0
A O 0
group O 0
, O 0
and O 0
cough B-Disease 0
was O 0
reported O 0
in O 0
3 O 0
. O 0
8 O 0
% O 0
patients O 0
( O 0
4 O 0
/ O 0
106 O 0
) O 0
in O 0
the O 0
T O 0
+ O 0
A O 0
group O 0
and O 0
1 O 0
. O 0
0 O 0
% O 0
( O 0
1 O 0
/ O 0
104 O 0
) O 0
patients O 0
in O 0
the O 0
A O 0
group O 0
; O 0
these O 0
differences O 0
did O 0
not O 0
reach O 0
statistical O 0
significance O 0
. O 0

The O 0
incidences O 0
of O 0
headache B-Disease 0
, O 0
dizziness B-Disease 0
, O 0
and O 0
diarrhea B-Disease 0
were O 0
similar O 0
between O 0
the O 0
2 O 0
groups O 0
. O 0

CONCLUSIONS O 0
: O 0
Among O 0
these O 0
Indian O 0
patients O 0
with O 0
stage O 0
II O 0
hypertension B-Disease 0
, O 0
the O 0
FDC O 0
of O 0
T O 0
+ O 0
A O 0
was O 0
found O 0
to O 0
be O 0
significantly O 0
more O 0
effective O 0
, O 0
with O 0
regard O 0
to O 0
BP O 0
reductions O 0
, O 0
than O 0
A O 0
, O 0
and O 0
both O 0
treatments O 0
were O 0
well O 0
tolerated O 0
. O 0

Increased O 0
mental B-Disease 0
slowing I-Disease 0
associated O 0
with O 0
the O 0
APOE O 0
epsilon4 O 0
allele O 0
after O 0
trihexyphenidyl B-Chemical 0
oral O 0
anticholinergic O 0
challenge O 0
in O 0
healthy O 0
elderly O 0
. O 0

OBJECTIVES O 0
: O 0
The O 0
objectives O 0
of O 0
this O 0
study O 0
were O 0
to O 0
examine O 0
the O 0
relationship O 0
between O 0
APOE O 0
epsilon4 O 0
and O 0
subjective O 0
effects O 0
of O 0
trihexyphenidyl B-Chemical 0
on O 0
measures O 0
reflecting O 0
sedation O 0
and O 0
confusion B-Disease 0
and O 0
to O 0
investigate O 0
the O 0
relationship O 0
between O 0
trihexyphenidyl B-Chemical 0
- O 0
induced O 0
subjective O 0
effects O 0
and O 0
objective O 0
memory O 0
performance O 0
. O 0

METHODS O 0
: O 0
This O 0
study O 0
comprised O 0
24 O 0
cognitively O 0
intact O 0
, O 0
health O 0
elderly O 0
adults O 0
( O 0
12 O 0
APOE O 0
epsilon4 O 0
carriers O 0
) O 0
at O 0
an O 0
outpatient O 0
geriatric O 0
psychiatry O 0
research O 0
clinic O 0
. O 0

This O 0
was O 0
a O 0
randomized O 0
, O 0
double O 0
blind O 0
, O 0
placebo O 0
- O 0
controlled O 0
, O 0
three O 0
- O 0
way O 0
, O 0
crossover O 0
experimental O 0
design O 0
. O 0

All O 0
participants O 0
received O 0
1 O 0
. O 0
0 O 0
mg O 0
or O 0
2 O 0
. O 0
0 O 0
mg O 0
trihexyphenidyl B-Chemical 0
or O 0
placebo O 0
administered O 0
in O 0
counterbalanced O 0
sequences O 0
over O 0
a O 0
period O 0
of O 0
three O 0
consecutive O 0
weeks O 0
. O 0

Bond O 0
and O 0
Lader O 0
' O 0
s O 0
visual O 0
analog O 0
scales O 0
and O 0
alternate O 0
versions O 0
of O 0
the O 0
Buschke O 0
Selective O 0
Reminding O 0
Test O 0
were O 0
administered O 0
in O 0
a O 0
repeated O 0
measures O 0
design O 0
at O 0
baseline O 0
, O 0
1 O 0
, O 0
2 O 0
. O 0
5 O 0
, O 0
and O 0
5 O 0
hours O 0
postdrug O 0
administration O 0
. O 0

RESULTS O 0
: O 0
A O 0
2 O 0
. O 0
0 O 0
- O 0
mg O 0
oral O 0
dose O 0
of O 0
trihexyphenidyl B-Chemical 0
resulted O 0
in O 0
increased O 0
subjective O 0
ratings O 0
of O 0
mental B-Disease 0
slowness I-Disease 0
in O 0
carriers O 0
of O 0
the O 0
APOE O 0
epsilon4 O 0
allele O 0
only O 0
. O 0

Drug O 0
effects O 0
as O 0
determined O 0
by O 0
difference O 0
scores O 0
between O 0
2 O 0
. O 0
0 O 0
mg O 0
trihexyphenidyl B-Chemical 0
and O 0
placebo O 0
on O 0
ratings O 0
of O 0
mental B-Disease 0
slowness I-Disease 0
significantly O 0
correlated O 0
with O 0
total O 0
and O 0
delayed O 0
recall O 0
on O 0
the O 0
Buschke O 0
Selective O 0
Reminding O 0
Test O 0
in O 0
carriers O 0
of O 0
the O 0
APOE O 0
epsilon4 O 0
allele O 0
only O 0
. O 0

However O 0
, O 0
no O 0
significant O 0
effects O 0
were O 0
found O 0
with O 0
other O 0
visual O 0
analog O 0
scales O 0
reflecting O 0
subjective O 0
sedation O 0
and O 0
clear O 0
- O 0
headedness O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
epsilon4 O 0
allele O 0
in O 0
healthy O 0
elderly O 0
was O 0
associated O 0
with O 0
increased O 0
subjective O 0
mental B-Disease 0
slowing I-Disease 0
after O 0
trihexyphenidyl B-Chemical 0
anticholinergic O 0
challenge O 0
. O 0

An O 0
evaluation O 0
of O 0
amikacin B-Chemical 0
nephrotoxicity B-Disease 0
in O 0
the O 0
hematology O 0
/ O 0
oncology O 0
population O 0
. O 0

Amikacin B-Chemical 0
is O 0
an O 0
aminoglycoside B-Chemical 0
commonly O 0
used O 0
to O 0
provide O 0
empirical O 0
double O 0
gram O 0
- O 0
negative O 0
treatment O 0
for O 0
febrile B-Disease 0
neutropenia I-Disease 0
and O 0
other O 0
suspected O 0
infections B-Disease 0
. O 0

Strategies O 0
of O 0
extended O 0
- O 0
interval O 0
and O 0
conventional O 0
dosing O 0
have O 0
been O 0
utilized O 0
extensively O 0
in O 0
the O 0
general O 0
medical O 0
population O 0
; O 0
however O 0
, O 0
data O 0
are O 0
lacking O 0
to O 0
support O 0
a O 0
dosing O 0
strategy O 0
in O 0
the O 0
hematology O 0
/ O 0
oncology O 0
population O 0
. O 0

To O 0
evaluate O 0
amikacin B-Chemical 0
- O 0
associated O 0
nephrotoxicity B-Disease 0
in O 0
an O 0
adult O 0
hematology O 0
/ O 0
oncology O 0
population O 0
, O 0
a O 0
prospective O 0
, O 0
randomized O 0
, O 0
open O 0
- O 0
label O 0
trial O 0
was O 0
conducted O 0
at O 0
a O 0
university O 0
- O 0
affiliated O 0
medical O 0
center O 0
. O 0

Forty O 0
patients O 0
with O 0
a O 0
diagnosis O 0
consistent O 0
with O 0
a O 0
hematologic B-Disease 0
/ I-Disease 0
oncologic I-Disease 0
disorder I-Disease 0
that O 0
required O 0
treatment O 0
with O 0
an O 0
aminoglycoside B-Chemical 0
were O 0
randomized O 0
to O 0
either O 0
conventional O 0
or O 0
extended O 0
- O 0
interval O 0
amikacin B-Chemical 0
. O 0

The O 0
occurrence O 0
of O 0
nephrotoxicity B-Disease 0
by O 0
means O 0
of O 0
an O 0
increase O 0
in O 0
serum O 0
creatinine B-Chemical 0
and O 0
evaluation O 0
of O 0
efficacy O 0
via O 0
amikacin B-Chemical 0
serum O 0
concentrations O 0
with O 0
respective O 0
pathogens O 0
were O 0
assessed O 0
. O 0

The O 0
occurrence O 0
of O 0
nephrotoxicity B-Disease 0
was O 0
similar O 0
between O 0
the O 0
conventional O 0
and O 0
extended O 0
- O 0
interval O 0
groups O 0
, O 0
at O 0
10 O 0
% O 0
and O 0
5 O 0
% O 0
, O 0
respectively O 0
( O 0
P O 0
= O 0
1 O 0
. O 0
00 O 0
) O 0
. O 0

Six O 0
patients O 0
in O 0
the O 0
conventional O 0
group O 0
had O 0
a O 0
positive O 0
culture O 0
, O 0
compared O 0
with O 0
none O 0
in O 0
the O 0
extended O 0
- O 0
interval O 0
group O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
002 O 0
) O 0
. O 0

The O 0
occurrence O 0
of O 0
nephrotoxicity B-Disease 0
was O 0
similar O 0
between O 0
the O 0
two O 0
dosing O 0
regimens O 0
, O 0
but O 0
the O 0
distribution O 0
of O 0
risk O 0
factors O 0
was O 0
variable O 0
between O 0
the O 0
two O 0
groups O 0
. O 0

Efficacy O 0
could O 0
not O 0
be O 0
assessed O 0
. O 0

High O 0
dose O 0
dexmedetomidine B-Chemical 0
as O 0
the O 0
sole O 0
sedative O 0
for O 0
pediatric O 0
MRI O 0
. O 0

OBJECTIVE O 0
: O 0
This O 0
large O 0
- O 0
scale O 0
retrospective O 0
review O 0
evaluates O 0
the O 0
sedation O 0
profile O 0
of O 0
dexmedetomidine B-Chemical 0
. O 0

AIM O 0
: O 0
To O 0
determine O 0
the O 0
hemodynamic O 0
responses O 0
, O 0
efficacy O 0
and O 0
adverse O 0
events O 0
associated O 0
with O 0
the O 0
use O 0
of O 0
high O 0
dose O 0
dexmedetomidine B-Chemical 0
as O 0
the O 0
sole O 0
sedative O 0
for O 0
magnetic O 0
resonance O 0
imaging O 0
( O 0
MRI O 0
) O 0
studies O 0
. O 0

BACKGROUND O 0
: O 0
Dexmedetomidine B-Chemical 0
has O 0
been O 0
used O 0
at O 0
our O 0
institution O 0
since O 0
2005 O 0
to O 0
provide O 0
sedation O 0
for O 0
pediatric O 0
radiological O 0
imaging O 0
studies O 0
. O 0

Over O 0
time O 0
, O 0
an O 0
effective O 0
protocol O 0
utilizing O 0
high O 0
dose O 0
dexmedetomidine B-Chemical 0
as O 0
the O 0
sole O 0
sedative O 0
agent O 0
has O 0
evolved O 0
. O 0

METHODS O 0
/ O 0
MATERIALS O 0
: O 0
As O 0
part O 0
of O 0
the O 0
ongoing O 0
Quality O 0
Assurance O 0
process O 0
, O 0
data O 0
on O 0
all O 0
sedations O 0
are O 0
reviewed O 0
monthly O 0
and O 0
protocols O 0
modified O 0
as O 0
needed O 0
. O 0

Data O 0
were O 0
analyzed O 0
from O 0
all O 0
747 O 0
consecutive O 0
patients O 0
who O 0
received O 0
dexmedetomidine B-Chemical 0
for O 0
MRI O 0
sedation O 0
from O 0
April O 0
2005 O 0
to O 0
April O 0
2007 O 0
. O 0

RESULTS O 0
: O 0
Since O 0
2005 O 0
, O 0
the O 0
10 O 0
- O 0
min O 0
loading O 0
dose O 0
of O 0
our O 0
dexmedetomidine B-Chemical 0
protocol O 0
increased O 0
from O 0
2 O 0
to O 0
3 O 0
microg O 0
. O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
, O 0
and O 0
the O 0
infusion O 0
rate O 0
increased O 0
from O 0
1 O 0
to O 0
1 O 0
. O 0
5 O 0
to O 0
2 O 0
microg O 0
. O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
. O 0
h O 0
( O 0
- O 0
1 O 0
) O 0
. O 0

The O 0
current O 0
sedation O 0
protocol O 0
progressively O 0
increased O 0
the O 0
rate O 0
of O 0
successful O 0
sedation O 0
( O 0
able O 0
to O 0
complete O 0
the O 0
imaging O 0
study O 0
) O 0
when O 0
using O 0
dexmedetomidine B-Chemical 0
alone O 0
from O 0
91 O 0
. O 0
8 O 0
% O 0
to O 0
97 O 0
. O 0
6 O 0
% O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
009 O 0
) O 0
, O 0
reducing O 0
the O 0
requirement O 0
for O 0
adjuvant O 0
pentobarbital B-Chemical 0
in O 0
the O 0
event O 0
of O 0
sedation O 0
failure O 0
with O 0
dexmedetomidine B-Chemical 0
alone O 0
and O 0
decreased O 0
the O 0
mean O 0
recovery O 0
time O 0
by O 0
10 O 0
min O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Although O 0
dexmedetomidine B-Chemical 0
sedation O 0
was O 0
associated O 0
with O 0
a O 0
16 O 0
% O 0
incidence O 0
of O 0
bradycardia B-Disease 0
, O 0
all O 0
concomitant O 0
mean O 0
arterial O 0
blood O 0
pressures O 0
were O 0
within O 0
20 O 0
% O 0
of O 0
age O 0
- O 0
adjusted O 0
normal O 0
range O 0
and O 0
oxygen B-Chemical 0
saturations O 0
were O 0
95 O 0
% O 0
or O 0
higher O 0
. O 0

CONCLUSION O 0
: O 0
Dexmedetomidine B-Chemical 0
in O 0
high O 0
doses O 0
provides O 0
adequate O 0
sedation O 0
for O 0
pediatric O 0
MRI O 0
studies O 0
. O 0

While O 0
use O 0
of O 0
high O 0
dose O 0
dexmedetomidine B-Chemical 0
is O 0
associated O 0
with O 0
decreases O 0
in O 0
heart O 0
rate O 0
and O 0
blood O 0
pressure O 0
outside O 0
the O 0
established O 0
' O 0
awake O 0
' O 0
norms O 0
, O 0
this O 0
deviation O 0
is O 0
generally O 0
within O 0
20 O 0
% O 0
of O 0
norms O 0
, O 0
and O 0
is O 0
not O 0
associated O 0
with O 0
adverse O 0
sequelae O 0
. O 0

Dexmedetomidine B-Chemical 0
is O 0
useful O 0
as O 0
the O 0
sole O 0
sedative O 0
for O 0
pediatric O 0
MRI O 0
. O 0

Hepatotoxicity B-Disease 0
associated O 0
with O 0
sulfasalazine B-Chemical 0
in O 0
inflammatory O 0
arthritis B-Disease 0
: O 0
A O 0
case O 0
series O 0
from O 0
a O 0
local O 0
surveillance O 0
of O 0
serious O 0
adverse O 0
events O 0
. O 0

BACKGROUND O 0
: O 0
Spontaneous O 0
reporting O 0
systems O 0
for O 0
adverse O 0
drug O 0
reactions O 0
( O 0
ADRs O 0
) O 0
are O 0
handicapped O 0
by O 0
under O 0
- O 0
reporting O 0
and O 0
limited O 0
detail O 0
on O 0
individual O 0
cases O 0
. O 0

We O 0
report O 0
an O 0
investigation O 0
from O 0
a O 0
local O 0
surveillance O 0
for O 0
serious O 0
adverse O 0
drug O 0
reactions O 0
associated O 0
with O 0
disease O 0
modifying O 0
anti O 0
- O 0
rheumatic O 0
drugs O 0
that O 0
was O 0
triggered O 0
by O 0
the O 0
occurrence O 0
of O 0
liver B-Disease 0
failure I-Disease 0
in O 0
two O 0
of O 0
our O 0
patients O 0
. O 0

METHODS O 0
: O 0
Serious O 0
ADR O 0
reports O 0
have O 0
been O 0
solicited O 0
from O 0
local O 0
clinicians O 0
by O 0
regular O 0
postcards O 0
over O 0
the O 0
past O 0
seven O 0
years O 0
. O 0

Patients O 0
' O 0
, O 0
who O 0
had O 0
hepatotoxicity B-Disease 0
on O 0
sulfasalazine B-Chemical 0
and O 0
met O 0
a O 0
definition O 0
of O 0
a O 0
serious O 0
ADR O 0
, O 0
were O 0
identified O 0
. O 0

Two O 0
clinicians O 0
reviewed O 0
structured O 0
case O 0
reports O 0
and O 0
assessed O 0
causality O 0
by O 0
consensus O 0
and O 0
by O 0
using O 0
a O 0
causality O 0
assessment O 0
instrument O 0
. O 0

The O 0
likely O 0
frequency O 0
of O 0
hepatotoxicity B-Disease 0
with O 0
sulfasalazine B-Chemical 0
was O 0
estimated O 0
by O 0
making O 0
a O 0
series O 0
of O 0
conservative O 0
assumptions O 0
. O 0

RESULTS O 0
: O 0
Ten O 0
cases O 0
were O 0
identified O 0
: O 0
eight O 0
occurred O 0
during O 0
surveillance O 0
. O 0

Eight O 0
patients O 0
were O 0
hospitalised O 0
, O 0
two O 0
in O 0
hepatic B-Disease 0
failure I-Disease 0
- O 0
one O 0
died O 0
after O 0
a O 0
liver O 0
transplant O 0
. O 0

All O 0
but O 0
one O 0
event O 0
occurred O 0
within O 0
6 O 0
weeks O 0
of O 0
treatment O 0
. O 0

Seven O 0
patients O 0
had O 0
a O 0
skin B-Disease 0
rash I-Disease 0
, O 0
three O 0
eosinophilia B-Disease 0
and O 0
one O 0
interstitial B-Disease 0
nephritis I-Disease 0
. O 0

Five O 0
patients O 0
were O 0
of O 0
Black O 0
British O 0
of O 0
African O 0
or O 0
Caribbean O 0
descent O 0
. O 0

Liver O 0
enzymes O 0
showed O 0
a O 0
hepatocellular O 0
pattern O 0
in O 0
four O 0
cases O 0
and O 0
a O 0
mixed O 0
pattern O 0
in O 0
six O 0
. O 0

Drug O 0
- O 0
related O 0
hepatotoxicity B-Disease 0
was O 0
judged O 0
probable O 0
or O 0
highly O 0
probable O 0
in O 0
8 O 0
patients O 0
. O 0

The O 0
likely O 0
frequency O 0
of O 0
serious O 0
hepatotoxicity B-Disease 0
with O 0
sulfasalazine B-Chemical 0
was O 0
estimated O 0
at O 0
0 O 0
. O 0
4 O 0
% O 0
of O 0
treated O 0
patients O 0
. O 0

CONCLUSION O 0
: O 0
Serious O 0
hepatotoxicity B-Disease 0
associated O 0
with O 0
sulfasalazine B-Chemical 0
appears O 0
to O 0
be O 0
under O 0
- O 0
appreciated O 0
and O 0
intensive O 0
monitoring O 0
and O 0
vigilance O 0
in O 0
the O 0
first O 0
6 O 0
weeks O 0
of O 0
treatment O 0
is O 0
especially O 0
important O 0
. O 0

Complete O 0
atrioventricular B-Disease 0
block I-Disease 0
secondary O 0
to O 0
lithium B-Chemical 0
therapy O 0
. O 0

Sinus B-Disease 0
node I-Disease 0
dysfunction I-Disease 0
has O 0
been O 0
reported O 0
most O 0
frequently O 0
among O 0
the O 0
adverse O 0
cardiovascular O 0
effects O 0
of O 0
lithium B-Chemical 0
. O 0

In O 0
the O 0
present O 0
case O 0
, O 0
complete O 0
atrioventricular B-Disease 0
( I-Disease 0
AV I-Disease 0
) I-Disease 0
block I-Disease 0
with O 0
syncopal B-Disease 0
attacks I-Disease 0
developed O 0
secondary O 0
to O 0
lithium B-Chemical 0
therapy O 0
, O 0
necessitating O 0
permanent O 0
pacemaker O 0
implantation O 0
. O 0

Serum O 0
lithium B-Chemical 0
levels O 0
remained O 0
under O 0
or O 0
within O 0
the O 0
therapeutic O 0
range O 0
during O 0
the O 0
syncopal B-Disease 0
attacks I-Disease 0
. O 0

Lithium B-Chemical 0
should O 0
be O 0
used O 0
with O 0
extreme O 0
caution O 0
, O 0
especially O 0
in O 0
patients O 0
with O 0
mild O 0
disturbance O 0
of O 0
AV O 0
conduction O 0
. O 0

Exaggerated O 0
expression O 0
of O 0
inflammatory O 0
mediators O 0
in O 0
vasoactive O 0
intestinal O 0
polypeptide O 0
knockout O 0
( O 0
VIP O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
with O 0
cyclophosphamide B-Chemical 0
( O 0
CYP B-Chemical 0
) O 0
- O 0
induced O 0
cystitis B-Disease 0
. O 0

Vasoactive O 0
intestinal O 0
polypeptide O 0
( O 0
VIP O 0
) O 0
is O 0
an O 0
immunomodulatory O 0
neuropeptide O 0
distributed O 0
in O 0
micturition O 0
pathways O 0
. O 0

VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
exhibit O 0
altered O 0
bladder O 0
function O 0
and O 0
neurochemical O 0
properties O 0
in O 0
micturition O 0
pathways O 0
after O 0
cyclophosphamide B-Chemical 0
( O 0
CYP B-Chemical 0
) O 0
- O 0
induced O 0
cystitis B-Disease 0
. O 0

Given O 0
VIP O 0
' O 0
s O 0
role O 0
as O 0
an O 0
anti O 0
- O 0
inflammatory O 0
mediator O 0
, O 0
we O 0
hypothesized O 0
that O 0
VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
would O 0
exhibit O 0
enhanced O 0
inflammatory O 0
mediator O 0
expression O 0
after O 0
cystitis B-Disease 0
. O 0

A O 0
mouse O 0
inflammatory O 0
cytokine O 0
and O 0
receptor O 0
RT2 O 0
profiler O 0
array O 0
was O 0
used O 0
to O 0
determine O 0
regulated O 0
transcripts O 0
in O 0
the O 0
urinary O 0
bladder O 0
of O 0
wild O 0
type O 0
( O 0
WT O 0
) O 0
and O 0
VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
with O 0
or O 0
without O 0
CYP B-Chemical 0
- O 0
induced O 0
cystitis B-Disease 0
( O 0
150 O 0
mg O 0
/ O 0
kg O 0
; O 0
i O 0
. O 0
p O 0
. O 0
; O 0
48 O 0
h O 0
) O 0
. O 0

Four O 0
binary O 0
comparisons O 0
were O 0
made O 0
: O 0
WT O 0
control O 0
versus O 0
CYP B-Chemical 0
treatment O 0
( O 0
48 O 0
h O 0
) O 0
, O 0
VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
control O 0
versus O 0
CYP B-Chemical 0
treatment O 0
( O 0
48 O 0
h O 0
) O 0
, O 0
WT O 0
control O 0
versus O 0
VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
control O 0
, O 0
and O 0
WT O 0
with O 0
CYP B-Chemical 0
treatment O 0
( O 0
48 O 0
h O 0
) O 0
versus O 0
VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
with O 0
CYP B-Chemical 0
treatment O 0
( O 0
48 O 0
h O 0
) O 0
. O 0

The O 0
genes O 0
presented O 0
represent O 0
( O 0
1 O 0
) O 0
greater O 0
than O 0
1 O 0
. O 0
5 O 0
- O 0
fold O 0
change O 0
in O 0
either O 0
direction O 0
and O 0
( O 0
2 O 0
) O 0
the O 0
p O 0
value O 0
is O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
for O 0
the O 0
comparison O 0
being O 0
made O 0
. O 0

Several O 0
regulated O 0
genes O 0
were O 0
validated O 0
using O 0
enzyme O 0
- O 0
linked O 0
immunoassays O 0
including O 0
IL O 0
- O 0
1beta O 0
and O 0
CXCL1 O 0
. O 0

CYP B-Chemical 0
treatment O 0
significantly O 0
( O 0
p O 0
< O 0
or O 0
= O 0
0 O 0
. O 0
001 O 0
) O 0
increased O 0
expression O 0
of O 0
CXCL1 O 0
and O 0
IL O 0
- O 0
1beta O 0
in O 0
the O 0
urinary O 0
bladder O 0
of O 0
WT O 0
and O 0
VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
, O 0
but O 0
expression O 0
in O 0
VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
with O 0
CYP B-Chemical 0
treatment O 0
was O 0
significantly O 0
( O 0
p O 0
< O 0
or O 0
= O 0
0 O 0
. O 0
001 O 0
) O 0
greater O 0
( O 0
4 O 0
. O 0
2 O 0
- O 0
to O 0
13 O 0
- O 0
fold O 0
increase O 0
) O 0
than O 0
that O 0
observed O 0
in O 0
WT O 0
urinary O 0
bladder O 0
( O 0
3 O 0
. O 0
6 O 0
- O 0
to O 0
5 O 0
- O 0
fold O 0
increase O 0
) O 0
. O 0

The O 0
data O 0
suggest O 0
that O 0
in O 0
VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
with O 0
bladder B-Disease 0
inflammation I-Disease 0
, O 0
inflammatory O 0
mediators O 0
are O 0
increased O 0
above O 0
that O 0
observed O 0
in O 0
WT O 0
with O 0
CYP B-Chemical 0
. O 0

This O 0
shift O 0
in O 0
balance O 0
may O 0
contribute O 0
to O 0
increased O 0
bladder B-Disease 0
dysfunction I-Disease 0
in O 0
VIP O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
with O 0
bladder B-Disease 0
inflammation I-Disease 0
and O 0
altered O 0
neurochemical O 0
expression O 0
in O 0
micturition O 0
pathways O 0
. O 0

Debrisoquine B-Chemical 0
phenotype O 0
and O 0
the O 0
pharmacokinetics O 0
and O 0
beta O 0
- O 0
2 O 0
receptor O 0
pharmacodynamics O 0
of O 0
metoprolol B-Chemical 0
and O 0
its O 0
enantiomers O 0
. O 0

The O 0
metabolism O 0
of O 0
the O 0
cardioselective O 0
beta O 0
- O 0
blocker O 0
metoprolol B-Chemical 0
is O 0
under O 0
genetic O 0
control O 0
of O 0
the O 0
debrisoquine B-Chemical 0
/ O 0
sparteine B-Chemical 0
type O 0
. O 0

The O 0
two O 0
metabolic O 0
phenotypes O 0
, O 0
extensive O 0
( O 0
EM O 0
) O 0
and O 0
poor O 0
metabolizers O 0
( O 0
PM O 0
) O 0
, O 0
show O 0
different O 0
stereoselective O 0
metabolism O 0
, O 0
resulting O 0
in O 0
apparently O 0
higher O 0
beta O 0
- O 0
1 O 0
adrenoceptor O 0
antagonistic O 0
potency O 0
of O 0
racemic O 0
metoprolol B-Chemical 0
in O 0
EMs O 0
. O 0

We O 0
investigated O 0
if O 0
the O 0
latter O 0
also O 0
applies O 0
to O 0
the O 0
beta O 0
- O 0
2 O 0
adrenoceptor O 0
antagonism O 0
by O 0
metoprolol B-Chemical 0
. O 0

The O 0
drug O 0
effect O 0
studied O 0
was O 0
the O 0
antagonism O 0
by O 0
metoprolol B-Chemical 0
of O 0
terbutaline B-Chemical 0
- O 0
induced O 0
hypokalemia B-Disease 0
. O 0

By O 0
using O 0
pharmacokinetic O 0
pharmacodynamic O 0
modeling O 0
the O 0
pharmacodynamics O 0
of O 0
racemic O 0
metoprolol B-Chemical 0
and O 0
the O 0
active O 0
S O 0
- O 0
isomer O 0
, O 0
were O 0
quantitated O 0
in O 0
EMs O 0
and O 0
PMs O 0
in O 0
terms O 0
of O 0
IC50 O 0
values O 0
, O 0
representing O 0
metoprolol B-Chemical 0
plasma O 0
concentrations O 0
resulting O 0
in O 0
half O 0
- O 0
maximum O 0
receptor O 0
occupancy O 0
. O 0

Six O 0
EMs O 0
received O 0
0 O 0
. O 0
5 O 0
mg O 0
of O 0
terbutaline B-Chemical 0
s O 0
. O 0
c O 0
. O 0
on O 0
two O 0
different O 0
occasions O 0
: O 0
1 O 0
) O 0
1 O 0
hr O 0
after O 0
administration O 0
of O 0
a O 0
placebo O 0
and O 0
2 O 0
) O 0
1 O 0
hr O 0
after O 0
150 O 0
mg O 0
of O 0
metoprolol B-Chemical 0
p O 0
. O 0
o O 0
. O 0

Five O 0
PMs O 0
were O 0
studied O 0
according O 0
to O 0
the O 0
same O 0
protocol O 0
, O 0
except O 0
for O 0
a O 0
higher O 0
terbutaline B-Chemical 0
dose O 0
( O 0
0 O 0
. O 0
75 O 0
mg O 0
) O 0
on O 0
day O 0
2 O 0
. O 0

Blood O 0
samples O 0
for O 0
the O 0
analysis O 0
of O 0
plasma O 0
potassium B-Chemical 0
, O 0
terbutaline B-Chemical 0
, O 0
metoprolol B-Chemical 0
( O 0
racemic O 0
, O 0
R O 0
- O 0
and O 0
S O 0
- O 0
isomer O 0
) O 0
, O 0
and O 0
alpha B-Chemical 0
- I-Chemical 0
hydroxymetoprolol I-Chemical 0
concentrations O 0
were O 0
taken O 0
at O 0
regular O 0
time O 0
intervals O 0
, O 0
during O 0
8 O 0
hr O 0
after O 0
metoprolol B-Chemical 0
. O 0

In O 0
PMs O 0
, O 0
metoprolol B-Chemical 0
increased O 0
the O 0
terbutaline B-Chemical 0
area O 0
under O 0
the O 0
plasma O 0
concentration O 0
vs O 0
. O 0
time O 0
curve O 0
( O 0
+ O 0
67 O 0
% O 0
) O 0
. O 0

Higher O 0
metoprolol B-Chemical 0
/ O 0
alpha B-Chemical 0
- I-Chemical 0
hydroxymetoprolol I-Chemical 0
ratios O 0
in O 0
PMs O 0
were O 0
predictive O 0
for O 0
higher O 0
R O 0
- O 0
/ O 0
S O 0
- O 0
isomer O 0
ratios O 0
of O 0
unchanged O 0
drug O 0
. O 0

There O 0
was O 0
a O 0
difference O 0
in O 0
metoprolol B-Chemical 0
potency O 0
with O 0
higher O 0
racemic O 0
metoprolol B-Chemical 0
IC50 O 0
values O 0
in O 0
PMs O 0
( O 0
72 O 0
+ O 0
/ O 0
- O 0
7 O 0
ng O 0
. O 0
ml O 0
- O 0
1 O 0
) O 0
than O 0
EMs O 0
( O 0
42 O 0
+ O 0
/ O 0
- O 0
8 O 0
ng O 0
. O 0
ml O 0
- O 0
1 O 0
, O 0
P O 0
less O 0
than 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

The O 0
hemodynamics O 0
of O 0
oxytocin B-Chemical 0
and O 0
other O 0
vasoactive O 0
agents O 0
during O 0
neuraxial O 0
anesthesia O 0
for O 0
cesarean O 0
delivery O 0
: O 0
findings O 0
in O 0
six O 0
cases O 0
. O 0

Oxytocin B-Chemical 0
is O 0
a O 0
commonly O 0
used O 0
uterotonic O 0
that O 0
can O 0
cause O 0
significant O 0
and O 0
even O 0
fatal O 0
hypotension B-Disease 0
, O 0
particularly O 0
when O 0
given O 0
as O 0
a O 0
bolus O 0
. O 0

The O 0
resulting O 0
hypotension B-Disease 0
can O 0
be O 0
produced O 0
by O 0
a O 0
decrease O 0
in O 0
systemic O 0
vascular O 0
resistance O 0
or O 0
cardiac O 0
output O 0
through O 0
a O 0
decrease O 0
in O 0
venous O 0
return O 0
. O 0

Parturients O 0
with O 0
normal O 0
volume O 0
status O 0
, O 0
heart O 0
valves O 0
and O 0
pulmonary O 0
vasculature O 0
most O 0
often O 0
respond O 0
to O 0
this O 0
hypotension B-Disease 0
with O 0
a O 0
compensatory O 0
increase O 0
in O 0
heart O 0
rate O 0
and O 0
stroke B-Disease 0
volume O 0
. O 0

Oxytocin B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
at O 0
cesarean O 0
delivery O 0
may O 0
be O 0
incorrectly O 0
attributed O 0
to O 0
blood B-Disease 0
loss I-Disease 0
. O 0

Pulse O 0
power O 0
analysis O 0
( O 0
also O 0
called O 0
" O 0
pulse O 0
contour O 0
analysis O 0
" O 0
) O 0
of O 0
an O 0
arterial O 0
pressure O 0
wave O 0
form O 0
allows O 0
continuous O 0
evaluation O 0
of O 0
systemic O 0
vascular O 0
resistance O 0
and O 0
cardiac O 0
output O 0
in O 0
real O 0
time O 0
, O 0
thereby O 0
elucidating O 0
the O 0
causative O 0
factors O 0
behind O 0
changes O 0
in O 0
blood O 0
pressure O 0
. O 0

Pulse O 0
power O 0
analysis O 0
was O 0
conducted O 0
in O 0
six O 0
cases O 0
of O 0
cesarean O 0
delivery O 0
performed O 0
under O 0
neuraxial O 0
anesthesia O 0
. O 0

Hypotension B-Disease 0
in O 0
response O 0
to O 0
oxytocin B-Chemical 0
was O 0
associated O 0
with O 0
a O 0
decrease O 0
in O 0
systemic O 0
vascular O 0
resistance O 0
and O 0
a O 0
compensatory O 0
increase O 0
in O 0
stroke B-Disease 0
volume O 0
, O 0
heart O 0
rate O 0
and O 0
cardiac O 0
output O 0
. O 0

Pulse O 0
power O 0
analysis O 0
may O 0
be O 0
helpful O 0
in O 0
determining O 0
the O 0
etiology O 0
of O 0
and O 0
treating O 0
hypotension B-Disease 0
during O 0
cesarean O 0
delivery O 0
under O 0
neuraxial O 0
anesthesia O 0
. O 0

Protective O 0
effects O 0
of O 0
antithrombin O 0
on O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
nephrosis B-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
antithrombin O 0
, O 0
a O 0
plasma O 0
inhibitor O 0
of O 0
coagulation O 0
factors O 0
, O 0
in O 0
rats O 0
with O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
- O 0
induced O 0
nephrosis B-Disease 0
, O 0
which O 0
is O 0
an O 0
experimental O 0
model O 0
of O 0
human O 0
nephrotic B-Disease 0
syndrome I-Disease 0
. O 0

Antithrombin O 0
( O 0
50 O 0
or O 0
500 O 0
IU O 0
/ O 0
kg O 0
/ O 0
i O 0
. O 0
v O 0
. O 0
) O 0
was O 0
administered O 0
to O 0
rats O 0
once O 0
a O 0
day O 0
for O 0
10 O 0
days O 0
immediately O 0
after O 0
the O 0
injection O 0
of O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
( O 0
50 O 0
mg O 0
/ O 0
kg O 0
/ O 0
i O 0
. O 0
v O 0
. O 0
) O 0
. O 0

Treatment O 0
with O 0
antithrombin O 0
attenuated O 0
the O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
- O 0
induced O 0
hematological B-Disease 0
abnormalities I-Disease 0
. O 0

Puromycin B-Chemical 0
aminonucleoside I-Chemical 0
- O 0
induced O 0
renal B-Disease 0
dysfunction I-Disease 0
and O 0
hyperlipidemia B-Disease 0
were O 0
also O 0
suppressed O 0
. O 0

Histopathological O 0
examination O 0
revealed O 0
severe O 0
renal B-Disease 0
damage I-Disease 0
such O 0
as O 0
proteinaceous O 0
casts O 0
in O 0
tubuli O 0
and O 0
tubular O 0
expansion O 0
in O 0
the O 0
kidney O 0
of O 0
control O 0
rats O 0
, O 0
while O 0
an O 0
improvement O 0
of O 0
the O 0
damage O 0
was O 0
seen O 0
in O 0
antithrombin O 0
- O 0
treated O 0
rats O 0
. O 0

In O 0
addition O 0
, O 0
antithrombin O 0
treatment O 0
markedly O 0
suppressed O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
- O 0
induced O 0
apoptosis O 0
of O 0
renal O 0
tubular O 0
epithelial O 0
cells O 0
. O 0

Furthermore O 0
, O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
- O 0
induced O 0
increases O 0
in O 0
renal O 0
cytokine O 0
content O 0
were O 0
also O 0
decreased O 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
thrombin O 0
plays O 0
an O 0
important O 0
role O 0
in O 0
the O 0
pathogenesis O 0
of O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
- O 0
induced O 0
nephrotic B-Disease 0
syndrome I-Disease 0
. O 0

Treatment O 0
with O 0
antithrombin O 0
may O 0
be O 0
clinically O 0
effective O 0
in O 0
patients O 0
with O 0
nephrotic B-Disease 0
syndrome I-Disease 0
. O 0

Heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
after O 0
liver O 0
transplantation O 0
. O 0

BACKGROUND O 0
: O 0
Unfractionated B-Chemical 0
heparin I-Chemical 0
sodium I-Chemical 0
( O 0
UFH B-Chemical 0
) O 0
or O 0
low B-Chemical 0
- I-Chemical 0
molecular I-Chemical 0
weight I-Chemical 0
heparin I-Chemical 0
( O 0
LMWH O 0
) O 0
is O 0
used O 0
in O 0
anticoagulant O 0
protocols O 0
at O 0
several O 0
institutions O 0
to O 0
prevent O 0
thrombosis B-Disease 0
after O 0
liver O 0
transplantation 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
is O 0
an O 0
adverse O 0
immune O 0
- O 0
mediated O 0
reaction O 0
to O 0
heparin B-Chemical 0
, O 0
resulting O 0
in O 0
platelet O 0
count O 0
decreases O 0
of O 0
more O 0
than O 0
50 O 0
% O 0
. O 0

The O 0
frequencies O 0
of O 0
HIT B-Disease 0
after O 0
liver O 0
transplantation O 0
and O 0
platelet O 0
factor O 0
4 O 0
/ O 0
heparin B-Chemical 0
- O 0
reactive O 0
antibody O 0
( O 0
HIT B-Disease 0
antibody O 0
) O 0
positivity O 0
in O 0
liver O 0
transplantation O 0
patients O 0
, O 0
however O 0
, O 0
are O 0
unknown O 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
The O 0
32 O 0
men O 0
and O 0
20 O 0
women O 0
underwent O 0
living O 0
donor O 0
liver O 0
transplantation O 0
. O 0

We O 0
started O 0
LMWH O 0
( O 0
25 O 0
IU O 0
/ O 0
kg O 0
/ O 0
h O 0
) O 0
on O 0
postoperative O 0
day O 0
( O 0
POD O 0
) O 0
1 O 0
, O 0
switching O 0
to O 0
UFH B-Chemical 0
( O 0
5000 O 0
U O 0
/ O 0
d O 0
) O 0
on O 0
POD O 0
2 O 0
or O 0
3 O 0
. O 0

The O 0
dose O 0
of O 0
UFH B-Chemical 0
was O 0
changed O 0
according O 0
to O 0
the O 0
activated O 0
clotting O 0
time O 0
level O 0
. O 0

HIT B-Disease 0
antibody O 0
levels O 0
were O 0
measured O 0
the O 0
day O 0
before O 0
surgery O 0
and O 0
on O 0
POD O 0
7 O 0
and O 0
14 O 0
. O 0

Platelet O 0
count O 0
was O 0
measured O 0
daily O 0
for O 0
3 O 0
weeks O 0
. O 0

RESULTS O 0
: O 0
The O 0
average O 0
platelet O 0
counts O 0
preoperatively O 0
, O 0
and O 0
on O 0
POD O 0
7 O 0
, O 0
14 O 0
, O 0
and O 0
21 O 0
were O 0
65 O 0
, O 0
88 O 0
, O 0
149 O 0
, O 0
and O 0
169 O 0
x O 0
10 O 0
( O 0
9 O 0
) O 0
/ O 0
L O 0
, O 0
respectively O 0
. O 0

Two O 0
patients O 0
developed O 0
hepatic O 0
artery O 0
thrombosis B-Disease 0
on O 0
POD O 0
11 O 0
and O 0
19 O 0
, O 0
respectively O 0
, O 0
although O 0
they O 0
were O 0
HIT B-Disease 0
antibody O 0
- O 0
negative O 0
and O 0
their O 0
platelet O 0
counts O 0
were O 0
stable O 0
. O 0

In O 0
2 O 0
other O 0
patients O 0
, O 0
the O 0
platelet O 0
count O 0
decreased O 0
suddenly O 0
from O 0
107 O 0
x O 0
10 O 0
( O 0
9 O 0
) O 0
/ O 0
L O 0
on O 0
POD O 0
4 O 0
to O 0
65 O 0
x O 0
10 O 0
( O 0
9 O 0
) O 0
/ O 0
L O 0
on O 0
POD O 0
6 O 0
and O 0
from O 0
76 O 0
x O 0
10 O 0
( O 0
9 O 0
) O 0
/ O 0
L O 0
on O 0
POD O 0
7 O 0
to O 0
33 O 0
x O 0
10 O 0
( O 0
9 O 0
) O 0
/ O 0
L O 0
on O 0
POD O 0
9 O 0
, O 0
respectively O 0
. O 0

The O 0
heparin B-Chemical 0
- O 0
induced O 0
platelet B-Disease 0
aggregation I-Disease 0
test O 0
was O 0
negative O 0
in O 0
these O 0
patients O 0
. O 0

The O 0
percentage O 0
of O 0
HIT B-Disease 0
antibody O 0
- O 0
positive O 0
patients O 0
was O 0
0 O 0
. O 0
5 O 0
% O 0
preoperatively O 0
, O 0
5 O 0
. O 0
6 O 0
% O 0
on O 0
POD O 0
7 O 0
, O 0
and O 0
5 O 0
. O 0
6 O 0
% O 0
on O 0
POD O 0
14 O 0
. O 0

None O 0
of O 0
the O 0
subjects O 0
/ O 0
patients O 0
developed O 0
UFH B-Chemical 0
- O 0
related O 0
HIT B-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
our O 0
series O 0
, O 0
the O 0
occurrence O 0
of O 0
HIT B-Disease 0
after O 0
liver O 0
transplantation O 0
was O 0
uncommon O 0
. O 0

Doxorubicin B-Chemical 0
cardiomyopathy B-Disease 0
- O 0
induced O 0
inflammation B-Disease 0
and O 0
apoptosis O 0
are O 0
attenuated O 0
by O 0
gene O 0
deletion O 0
of O 0
the O 0
kinin O 0
B1 O 0
receptor O 0
. O 0

Clinical O 0
use O 0
of O 0
the O 0
anthracycline B-Chemical 0
doxorubicin B-Chemical 0
( O 0
DOX B-Chemical 0
) O 0
is O 0
limited O 0
by O 0
its O 0
cardiotoxic B-Disease 0
effects O 0
, O 0
which O 0
are O 0
attributed O 0
to O 0
the O 0
induction O 0
of O 0
apoptosis O 0
. O 0

To O 0
elucidate O 0
the O 0
possible O 0
role O 0
of O 0
the O 0
kinin O 0
B1 O 0
receptor O 0
( O 0
B1R O 0
) O 0
during O 0
the O 0
development O 0
of O 0
DOX B-Chemical 0
cardiomyopathy B-Disease 0
, O 0
we O 0
studied O 0
B1R O 0
knockout O 0
mice O 0
( O 0
B1R O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
) O 0
by O 0
investigating O 0
cardiac O 0
inflammation B-Disease 0
and O 0
apoptosis O 0
after O 0
induction O 0
of O 0
DOX B-Chemical 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
. O 0

DOX B-Chemical 0
control O 0
mice O 0
showed O 0
cardiac B-Disease 0
dysfunction I-Disease 0
measured O 0
by O 0
pressure O 0
- O 0
volume O 0
loops O 0
in O 0
vivo O 0
. O 0

This O 0
was O 0
associated O 0
with O 0
a O 0
reduced O 0
activation O 0
state O 0
of O 0
AKT O 0
, O 0
as O 0
well O 0
as O 0
an O 0
increased O 0
bax O 0
/ O 0
bcl2 O 0
ratio O 0
in O 0
Western O 0
blots O 0
, O 0
indicating O 0
cardiac B-Disease 0
apoptosis I-Disease 0
. O 0

Furthermore O 0
, O 0
mRNA O 0
levels O 0
of O 0
the O 0
proinflammatory O 0
cytokine O 0
interleukin O 0
6 O 0
were O 0
increased O 0
in O 0
the O 0
cardiac O 0
tissue O 0
. O 0

In O 0
DOX B-Chemical 0
B1R O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
, O 0
cardiac B-Disease 0
dysfunction I-Disease 0
was O 0
improved O 0
compared O 0
to O 0
DOX B-Chemical 0
control O 0
mice O 0
, O 0
which O 0
was O 0
associated O 0
with O 0
normalization O 0
of O 0
the O 0
bax O 0
/ O 0
bcl O 0
- O 0
2 O 0
ratio O 0
and O 0
interleukin O 0
6 O 0
, O 0
as O 0
well O 0
as O 0
AKT O 0
activation O 0
state O 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
B1R O 0
is O 0
detrimental O 0
in O 0
DOX B-Chemical 0
cardiomyopathy B-Disease 0
in O 0
that O 0
it O 0
mediates O 0
the O 0
inflammatory O 0
response O 0
and O 0
apoptosis O 0
. O 0

These O 0
insights O 0
might O 0
have O 0
useful O 0
implications O 0
for O 0
future O 0
studies O 0
utilizing O 0
B1R O 0
antagonists O 0
for O 0
treatment O 0
of O 0
human O 0
DOX B-Chemical 0
cardiomyopathy B-Disease 0
. O 0

Detailed O 0
spectral O 0
profile O 0
analysis O 0
of O 0
penicillin B-Chemical 0
- O 0
induced O 0
epileptiform B-Disease 0
activity I-Disease 0
in O 0
anesthetized O 0
rats O 0
. O 0

Penicillin B-Chemical 0
model O 0
is O 0
a O 0
widely O 0
used O 0
experimental O 0
model O 0
for O 0
epilepsy B-Disease 0
research O 0
. O 0

In O 0
the O 0
present O 0
study O 0
we O 0
aimed O 0
to O 0
portray O 0
a O 0
detailed O 0
spectral O 0
analysis O 0
of O 0
penicillin B-Chemical 0
- O 0
induced O 0
epileptiform B-Disease 0
activity I-Disease 0
in O 0
comparison O 0
with O 0
basal O 0
brain O 0
activity O 0
in O 0
anesthetized O 0
Wistar O 0
rats O 0
. O 0

Male O 0
Wistar O 0
rats O 0
were O 0
anesthetized O 0
with O 0
i O 0
. O 0
p O 0
. O 0
urethane B-Chemical 0
and O 0
connected O 0
to O 0
an O 0
electrocorticogram O 0
setup O 0
. O 0

After O 0
a O 0
short O 0
period O 0
of O 0
basal O 0
activity O 0
recording O 0
, O 0
epileptic B-Disease 0
focus O 0
was O 0
induced O 0
by O 0
injecting O 0
400IU O 0
/ O 0
2 O 0
microl O 0
penicillin B-Chemical 0
- I-Chemical 0
G I-Chemical 0
potassium I-Chemical 0
into O 0
the O 0
left O 0
lateral O 0
ventricle O 0
while O 0
the O 0
cortical O 0
activity O 0
was O 0
continuously O 0
recorded O 0
. O 0

Basal O 0
activity O 0
, O 0
latent O 0
period O 0
and O 0
the O 0
penicillin B-Chemical 0
- O 0
induced O 0
epileptiform B-Disease 0
activity I-Disease 0
periods O 0
were O 0
then O 0
analyzed O 0
using O 0
both O 0
conventional O 0
methods O 0
and O 0
spectral O 0
analysis O 0
. O 0

Spectral O 0
analyses O 0
were O 0
conducted O 0
by O 0
dividing O 0
the O 0
whole O 0
spectrum O 0
into O 0
different O 0
frequency O 0
bands O 0
including O 0
delta O 0
, O 0
theta O 0
( O 0
slow O 0
and O 0
fast O 0
) O 0
, O 0
alpha O 0
- O 0
sigma O 0
, O 0
beta O 0
( O 0
1 O 0
and O 0
2 O 0
) O 0
and O 0
gamma O 0
( O 0
1 O 0
and O 0
2 O 0
) O 0
bands O 0
. O 0

Our O 0
results O 0
show O 0
that O 0
the O 0
most O 0
affected O 0
frequency O 0
bands O 0
were O 0
delta O 0
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theta O 0
, O 0
beta O 0
- O 0
2 O 0
and O 0
gamma O 0
- O 0
2 O 0
bands O 0
during O 0
the O 0
epileptiform B-Disease 0
activity I-Disease 0
and O 0
there O 0
were O 0
marked O 0
differences O 0
in O 0
terms O 0
of O 0
spectral O 0
densities O 0
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three O 0
investigated O 0
episodes O 0
( O 0
basal O 0
activity O 0
, O 0
latent O 0
period O 0
and O 0
epileptiform B-Disease 0
activity I-Disease 0
) O 0
. O 0

Our O 0
results O 0
may O 0
help O 0
to O 0
analyze O 0
novel O 0
data O 0
obtained O 0
using O 0
similar O 0
experimental O 0
models O 0
and O 0
the O 0
simple O 0
analysis O 0
method O 0
described O 0
here O 0
can O 0
be O 0
used O 0
in O 0
similar O 0
studies O 0
to O 0
investigate O 0
the O 0
basic O 0
neuronal O 0
mechanism O 0
of O 0
this O 0
or O 0
other O 0
types O 0
of O 0
experimental O 0
epilepsies B-Disease 0
. O 0

High O 0
fat B-Chemical 0
diet O 0
- O 0
fed O 0
obese B-Disease 0
rats O 0
are O 0
highly O 0
sensitive O 0
to O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

Often O 0
, O 0
chemotherapy O 0
by O 0
doxorubicin B-Chemical 0
( O 0
Adriamycin B-Chemical 0
) O 0
is O 0
limited O 0
due O 0
to O 0
life O 0
threatening O 0
cardiotoxicity B-Disease 0
in O 0
patients O 0
during O 0
and O 0
posttherapy O 0
. O 0

Recently O 0
, O 0
we O 0
have O 0
shown O 0
that O 0
moderate O 0
diet O 0
restriction O 0
remarkably O 0
protects O 0
against O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

This O 0
cardioprotection O 0
is O 0
accompanied O 0
by O 0
decreased O 0
cardiac O 0
oxidative O 0
stress O 0
and O 0
triglycerides B-Chemical 0
and O 0
increased O 0
cardiac O 0
fatty O 0
- O 0
acid O 0
oxidation O 0
, O 0
ATP B-Chemical 0
synthesis O 0
, O 0
and O 0
upregulated O 0
JAK O 0
/ O 0
STAT3 O 0
pathway O 0
. O 0

In O 0
the O 0
current O 0
study O 0
, O 0
we O 0
investigated O 0
whether O 0
a O 0
physiological O 0
intervention O 0
by O 0
feeding O 0
40 O 0
% O 0
high O 0
fat B-Chemical 0
diet O 0
( O 0
HFD O 0
) O 0
, O 0
which O 0
induces O 0
obesity B-Disease 0
in O 0
male O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
( O 0
250 O 0
- O 0
275 O 0
g O 0
) O 0
, O 0
sensitizes O 0
to O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
. O 0

A O 0
LD O 0
( O 0
10 O 0
) O 0
dose O 0
( O 0
8 O 0
mg O 0
doxorubicin B-Chemical 0
/ O 0
kg O 0
, O 0
ip O 0
) O 0
administered O 0
on O 0
day O 0
43 O 0
of O 0
the O 0
HFD O 0
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regimen O 0
led O 0
to O 0
higher O 0
cardiotoxicity B-Disease 0
, O 0
cardiac B-Disease 0
dysfunction I-Disease 0
, O 0
lipid O 0
peroxidation O 0
, O 0
and O 0
80 O 0
% O 0
mortality O 0
in O 0
the O 0
obese B-Disease 0
( O 0
OB B-Disease 0
) O 0
rats O 0
in O 0
the O 0
absence O 0
of O 0
any O 0
significant O 0
renal B-Disease 0
or I-Disease 0
hepatic I-Disease 0
toxicity I-Disease 0
. O 0

Doxorubicin B-Chemical 0
toxicokinetics O 0
studies O 0
revealed O 0
no O 0
change O 0
in O 0
accumulation O 0
of O 0
doxorubicin B-Chemical 0
and O 0
doxorubicinol B-Chemical 0
( O 0
toxic O 0
metabolite O 0
) O 0
in O 0
the O 0
normal O 0
diet O 0
- O 0
fed O 0
( O 0
ND O 0
) O 0
and O 0
OB B-Disease 0
hearts O 0
. O 0

Mechanistic O 0
studies O 0
revealed O 0
that O 0
OB B-Disease 0
rats O 0
are O 0
sensitized O 0
due O 0
to O 0
: O 0
( O 0
1 O 0
) O 0
higher O 0
oxyradical O 0
stress O 0
leading O 0
to O 0
upregulation O 0
of O 0
uncoupling O 0
proteins O 0
2 O 0
and O 0
3 O 0
, O 0
( O 0
2 O 0
) O 0
downregulation O 0
of O 0
cardiac O 0
peroxisome O 0
proliferators O 0
activated O 0
receptor O 0
- O 0
alpha O 0
, O 0
( O 0
3 O 0
) O 0
decreased O 0
plasma O 0
adiponectin O 0
levels O 0
, O 0
( O 0
4 O 0
) O 0
decreased O 0
cardiac O 0
fatty O 0
- O 0
acid O 0
oxidation O 0
( O 0
666 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
14 O 0
. O 0
0 O 0
nmol O 0
/ O 0
min O 0
/ O 0
g O 0
heart O 0
in O 0
ND O 0
versus O 0
400 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
11 O 0
. O 0
8 O 0
nmol O 0
/ O 0
min O 0
/ O 0
g O 0
heart O 0
in O 0
OB B-Disease 0
) O 0
, O 0
( O 0
5 O 0
) O 0
decreased O 0
mitochondrial O 0
AMP B-Chemical 0
- O 0
alpha2 O 0
protein O 0
kinase O 0
, O 0
and O 0
( O 0
6 O 0
) O 0
86 O 0
% O 0
drop O 0
in O 0
cardiac O 0
ATP B-Chemical 0
levels O 0
accompanied O 0
by O 0
decreased O 0
ATP B-Chemical 0
/ O 0
ADP B-Chemical 0
ratio O 0
after O 0
doxorubicin B-Chemical 0
administration O 0
. O 0

Decreased O 0
cardiac O 0
erythropoietin O 0
and O 0
increased O 0
SOCS3 O 0
further O 0
downregulated O 0
the O 0
cardioprotective O 0
JAK O 0
/ O 0
STAT3 O 0
pathway O 0
. O 0

In O 0
conclusion O 0
, O 0
HFD O 0
- O 0
induced O 0
obese B-Disease 0
rats O 0
are O 0
highly O 0
sensitized O 0
to O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
by O 0
substantially O 0
downregulating O 0
cardiac O 0
mitochondrial O 0
ATP B-Chemical 0
generation O 0
, O 0
increasing O 0
oxidative O 0
stress O 0
and O 0
downregulating O 0
the O 0
JAK O 0
/ O 0
STAT3 O 0
pathway O 0
. O 0

Isoproterenol B-Chemical 0
induces O 0
primary O 0
loss O 0
of O 0
dystrophin O 0
in O 0
rat O 0
hearts O 0
: O 0
correlation O 0
with O 0
myocardial B-Disease 0
injury I-Disease 0
. O 0

The O 0
mechanism O 0
of O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
myocardial B-Disease 0
damage I-Disease 0
is O 0
unknown O 0
, O 0
but O 0
a O 0
mismatch O 0
of O 0
oxygen B-Chemical 0
supply O 0
vs O 0
. O 0
demand O 0
following O 0
coronary O 0
hypotension B-Disease 0
and O 0
myocardial B-Disease 0
hyperactivity I-Disease 0
is O 0
the O 0
best O 0
explanation O 0
for O 0
the O 0
complex O 0
morphological O 0
alterations O 0
observed O 0
. O 0

Severe O 0
alterations O 0
in O 0
the O 0
structural O 0
integrity O 0
of O 0
the O 0
sarcolemma O 0
of O 0
cardiomyocytes O 0
have O 0
been O 0
demonstrated O 0
to O 0
be O 0
caused O 0
by O 0
isoproterenol B-Chemical 0
. O 0

Taking O 0
into O 0
account O 0
that O 0
the O 0
sarcolemmal O 0
integrity O 0
is O 0
stabilized O 0
by O 0
the O 0
dystrophin O 0
- O 0
glycoprotein O 0
complex O 0
( O 0
DGC O 0
) O 0
that O 0
connects O 0
actin O 0
and O 0
laminin O 0
in O 0
contractile O 0
machinery O 0
and O 0
extracellular O 0
matrix O 0
and O 0
by O 0
integrins O 0
, O 0
this O 0
study O 0
tests O 0
the O 0
hypothesis O 0
that O 0
isoproterenol B-Chemical 0
affects O 0
sarcolemmal O 0
stability O 0
through O 0
changes O 0
in O 0
the O 0
DGC O 0
and O 0
integrins O 0
. O 0

We O 0
found O 0
different O 0
sensitivity O 0
of O 0
the O 0
DGC O 0
and O 0
integrin O 0
to O 0
isoproterenol B-Chemical 0
subcutaneous O 0
administration O 0
. O 0

Immunofluorescent O 0
staining O 0
revealed O 0
that O 0
dystrophin O 0
is O 0
the O 0
most O 0
sensitive O 0
among O 0
the O 0
structures O 0
connecting O 0
the O 0
actin O 0
in O 0
the O 0
cardiomyocyte O 0
cytoskeleton O 0
and O 0
the O 0
extracellular O 0
matrix O 0
. O 0

The O 0
sarcomeric O 0
actin O 0
dissolution O 0
occurred O 0
after O 0
the O 0
reduction O 0
or O 0
loss O 0
of O 0
dystrophin O 0
. O 0

Subsequently O 0
, O 0
after O 0
lysis O 0
of O 0
myofilaments O 0
, O 0
gamma O 0
- O 0
sarcoglycan O 0
, O 0
beta O 0
- O 0
dystroglycan O 0
, O 0
beta1 O 0
- O 0
integrin O 0
, O 0
and O 0
laminin O 0
alpha O 0
- O 0
2 O 0
expressions O 0
were O 0
reduced O 0
followed O 0
by O 0
their O 0
breakdown O 0
, O 0
as O 0
epiphenomena O 0
of O 0
the O 0
myocytolytic O 0
process O 0
. O 0

In O 0
conclusion O 0
, O 0
administration O 0
of O 0
isoproterenol B-Chemical 0
to O 0
rats O 0
results O 0
in O 0
primary O 0
loss O 0
of O 0
dystrophin O 0
, O 0
the O 0
most O 0
sensitive O 0
among O 0
the O 0
structural O 0
proteins O 0
that O 0
form O 0
the O 0
DGC O 0
that O 0
connects O 0
the O 0
extracellular O 0
matrix O 0
and O 0
the O 0
cytoskeleton O 0
in O 0
cardiomyocyte O 0
. O 0

These O 0
changes O 0
, O 0
related O 0
to O 0
ischaemic B-Disease 0
injury I-Disease 0
, O 0
explain O 0
the O 0
severe O 0
alterations O 0
in O 0
the O 0
structural O 0
integrity O 0
of O 0
the O 0
sarcolemma O 0
of O 0
cardiomyocytes O 0
and O 0
hence O 0
severe O 0
and O 0
irreversible O 0
injury O 0
induced O 0
by O 0
isoproterenol B-Chemical 0
. O 0

Etiologic O 0
factors O 0
in O 0
the O 0
pathogenesis O 0
of O 0
liver B-Disease 0
tumors I-Disease 0
associated O 0
with O 0
oral B-Chemical 0
contraceptives I-Chemical 0
. O 0

Within O 0
the O 0
last O 0
several O 0
years O 0
, O 0
previously O 0
rare O 0
liver B-Disease 0
tumors I-Disease 0
have O 0
been O 0
seen O 0
in O 0
young O 0
women O 0
using O 0
oral B-Chemical 0
contraceptive I-Chemical 0
steroids B-Chemical 0
. O 0

The O 0
Registry O 0
for O 0
Liver B-Disease 0
Tumors I-Disease 0
Associated O 0
with O 0
Oral B-Chemical 0
Contraceptives I-Chemical 0
at O 0
the O 0
University O 0
of O 0
California O 0
, O 0
Irvine O 0
, O 0
has O 0
clearly O 0
identified O 0
27 O 0
cases O 0
. O 0

The O 0
recent O 0
literature O 0
contains O 0
44 O 0
case O 0
reports O 0
. O 0

Common O 0
to O 0
these O 0
71 O 0
cases O 0
has O 0
been O 0
a O 0
histopathologic O 0
diagnosis O 0
of O 0
focal B-Disease 0
nodular I-Disease 0
hyperplasia I-Disease 0
, O 0
adenoma B-Disease 0
, O 0
hamartoma B-Disease 0
, O 0
and O 0
hepatoma B-Disease 0
. O 0

Significant O 0
statistical O 0
etiologic O 0
factors O 0
include O 0
prolonged O 0
uninterrupted O 0
usage O 0
of O 0
oral B-Chemical 0
contraceptive I-Chemical 0
steroids B-Chemical 0
. O 0

Eight O 0
deaths O 0
and O 0
liver O 0
rupture B-Disease 0
in O 0
18 O 0
patients O 0
attest O 0
to O 0
the O 0
seriousness O 0
of O 0
this O 0
new O 0
potentially O 0
lethal O 0
adverse O 0
phenomenon O 0
. O 0

Ifosfamide B-Chemical 0
continuous O 0
infusion O 0
without O 0
mesna B-Chemical 0
. O 0

A O 0
phase O 0
I O 0
trial O 0
of O 0
a O 0
14 O 0
- O 0
day O 0
cycle O 0
. O 0

Twenty O 0
patients O 0
received O 0
27 O 0
courses O 0
of O 0
ifosfamide B-Chemical 0
administered O 0
as O 0
a O 0
24 O 0
- O 0
hour O 0
continuous O 0
infusion O 0
for O 0
14 O 0
days O 0
without O 0
Mesna B-Chemical 0
. O 0

The O 0
goal O 0
of O 0
the O 0
study O 0
was O 0
to O 0
deliver O 0
a O 0
dose O 0
rate O 0
and O 0
total O 0
cumulative O 0
dose O 0
of O 0
ifosfamide B-Chemical 0
that O 0
would O 0
be O 0
comparable O 0
to O 0
standard O 0
bolus O 0
or O 0
short O 0
- O 0
term O 0
infusions O 0
administered O 0
with O 0
Mesna B-Chemical 0
. O 0

Dose O 0
escalations O 0
proceeded O 0
from O 0
200 O 0
to O 0
300 O 0
, O 0
400 O 0
, O 0
450 O 0
, O 0
500 O 0
, O 0
and O 0
550 O 0
mg O 0
/ O 0
m2 O 0
/ O 0
d O 0
. O 0

Four O 0
patients O 0
developed O 0
transient O 0
microscopic O 0
hematuria B-Disease 0
at O 0
400 O 0
, O 0
450 O 0
, O 0
and O 0
500 O 0
mg O 0
/ O 0
m2 O 0
/ O 0
d O 0
. O 0

There O 0
were O 0
no O 0
instances O 0
of O 0
macroscopic O 0
hematuria B-Disease 0
. O 0

At O 0
550 O 0
mg O 0
/ O 0
m2 O 0
/ O 0
d O 0
, O 0
three O 0
patients O 0
experienced O 0
nonurologic O 0
toxicity B-Disease 0
; O 0
confusion B-Disease 0
( O 0
1 O 0
) O 0
, O 0
nausea B-Disease 0
( O 0
1 O 0
) O 0
, O 0
and O 0
Grade O 0
2 O 0
leukopenia B-Disease 0
( O 0
1 O 0
) O 0
. O 0

The O 0
recommended O 0
dose O 0
of O 0
500 O 0
mg O 0
/ O 0
m2 O 0
/ O 0
d O 0
delivers O 0
a O 0
total O 0
dose O 0
of O 0
7 O 0
g O 0
/ O 0
m2 O 0
per O 0
cycle O 0
, O 0
which O 0
is O 0
comparable O 0
to O 0
that O 0
delivered O 0
in O 0
clinical O 0
practice O 0
for O 0
bolus O 0
or O 0
short O 0
- O 0
term O 0
infusion O 0
. O 0

Because O 0
few O 0
patients O 0
received O 0
multiple O 0
courses O 0
over O 0
time O 0
, O 0
the O 0
cumulative O 0
effects O 0
are O 0
indeterminate O 0
in O 0
the O 0
present O 0
trial O 0
. O 0

The O 0
frequency O 0
and O 0
predictability O 0
of O 0
hematuria B-Disease 0
are O 0
not O 0
precise O 0
, O 0
and O 0
at O 0
least O 0
daily O 0
monitoring O 0
by O 0
urine O 0
Hematest O 0
is O 0
essential O 0
, O 0
adding O 0
Mesna B-Chemical 0
to O 0
the O 0
infusate O 0
in O 0
patients O 0
with O 0
persistent O 0
hematuria B-Disease 0
. O 0

The O 0
protracted O 0
infusion O 0
schedule O 0
for O 0
ifosfamide B-Chemical 0
permits O 0
convenient O 0
outpatient O 0
administration O 0
without O 0
Mesna B-Chemical 0
and O 0
reduces O 0
the O 0
drug O 0
cost O 0
of O 0
clinical O 0
usage O 0
of O 0
this O 0
agent O 0
by O 0
up O 0
to O 0
890 O 0
per O 0
cycle O 0
. O 0

Clinical O 0
activity O 0
was O 0
demonstrated O 0
in O 0
a O 0
single O 0
patient O 0
, O 0
but O 0
a O 0
comparative O 0
trial O 0
of O 0
standard O 0
bolus O 0
schedules O 0
with O 0
the O 0
protracted O 0
infusion O 0
schedule O 0
will O 0
be O 0
necessary O 0
to O 0
determine O 0
if O 0
the O 0
clinical O 0
effectiveness O 0
of O 0
the O 0
drug O 0
is O 0
maintained O 0
. O 0

A O 0
case O 0
of O 0
ventricular B-Disease 0
tachycardia I-Disease 0
related O 0
to O 0
caffeine B-Chemical 0
pretreatment O 0
. O 0

Suboptimal O 0
seizure B-Disease 0
duration O 0
is O 0
commonly O 0
encountered O 0
in O 0
electroconvulsive O 0
therapy O 0
practice O 0
, O 0
especially O 0
in O 0
older O 0
patients O 0
with O 0
higher O 0
seizure B-Disease 0
thresholds O 0
. O 0

Intravenous O 0
caffeine B-Chemical 0
is O 0
commonly O 0
used O 0
to O 0
improve O 0
seizure B-Disease 0
duration O 0
and O 0
quality O 0
in O 0
such O 0
patients O 0
and O 0
is O 0
generally O 0
well O 0
tolerated O 0
aside O 0
from O 0
occasional O 0
reports O 0
of O 0
relatively O 0
benign O 0
ventricular B-Disease 0
ectopy I-Disease 0
. O 0

We O 0
describe O 0
a O 0
patient O 0
with O 0
no O 0
previous O 0
history O 0
of O 0
cardiac B-Disease 0
disease I-Disease 0
or O 0
arrhythmia B-Disease 0
who O 0
developed O 0
sustained O 0
bigeminy O 0
and O 0
2 O 0
brief O 0
runs O 0
of O 0
ventricular B-Disease 0
tachycardia I-Disease 0
after O 0
caffeine B-Chemical 0
administration O 0
. O 0

Although O 0
intravenous O 0
caffeine B-Chemical 0
is O 0
generally O 0
well O 0
tolerated O 0
, O 0
the O 0
clinician O 0
should O 0
be O 0
aware O 0
of O 0
the O 0
potential O 0
for O 0
unpredictable O 0
and O 0
serious O 0
ventricular B-Disease 0
arrhythmias I-Disease 0
. O 0

Fatal O 0
haemopericardium B-Disease 0
and O 0
gastrointestinal B-Disease 0
haemorrhage I-Disease 0
due O 0
to O 0
possible O 0
interaction O 0
of O 0
cranberry O 0
juice O 0
with O 0
warfarin B-Chemical 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
fatal O 0
internal O 0
haemorrhage B-Disease 0
in O 0
an O 0
elderly O 0
man O 0
who O 0
consumed O 0
only O 0
cranberry O 0
juice O 0
for O 0
two O 0
weeks O 0
while O 0
maintaining O 0
his O 0
usual O 0
dosage O 0
of O 0
warfarin B-Chemical 0
. O 0

We O 0
propose O 0
that O 0
naturally O 0
occurring O 0
compounds O 0
such O 0
as O 0
flavonoids B-Chemical 0
, O 0
which O 0
are O 0
present O 0
in O 0
fruit O 0
juices O 0
, O 0
may O 0
increase O 0
the O 0
potency O 0
of O 0
warfarin B-Chemical 0
by O 0
competing O 0
for O 0
the O 0
enzymes O 0
that O 0
normally O 0
inactivate O 0
warfarin B-Chemical 0
. O 0

While O 0
traditionally O 0
regarded O 0
as O 0
foodstuffs O 0
, O 0
consumption O 0
of O 0
fruit O 0
juices O 0
should O 0
be O 0
considered O 0
when O 0
patients O 0
develop O 0
adverse O 0
drug O 0
reactions O 0
. O 0

Effect O 0
of O 0
increasing O 0
intraperitoneal O 0
infusion O 0
rates O 0
on O 0
bupropion B-Chemical 0
hydrochloride I-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
in O 0
mice O 0
. O 0

BACKGROUND O 0
: O 0
It O 0
is O 0
not O 0
known O 0
if O 0
there O 0
is O 0
a O 0
relationship O 0
between O 0
input O 0
rate O 0
and O 0
incidence O 0
of O 0
bupropion B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
. O 0

This O 0
is O 0
important O 0
, O 0
since O 0
different O 0
controlled O 0
release O 0
formulations O 0
of O 0
bupropion B-Chemical 0
release O 0
the O 0
active O 0
drug O 0
at O 0
different O 0
rates O 0
. O 0

METHODS O 0
: O 0
We O 0
investigated O 0
the O 0
effect O 0
of O 0
varying O 0
the O 0
intraperitoneal O 0
infusion O 0
rates O 0
of O 0
bupropion B-Chemical 0
HCl I-Chemical 0
120 O 0
mg O 0
/ O 0
kg O 0
, O 0
a O 0
known O 0
convulsive B-Disease 0
dose O 0
50 O 0
( O 0
CD50 O 0
) O 0
, O 0
on O 0
the O 0
incidence O 0
and O 0
severity O 0
of O 0
bupropion B-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
in O 0
the O 0
Swiss O 0
albino O 0
mice O 0
. O 0

A O 0
total O 0
of O 0
69 O 0
mice O 0
, O 0
approximately O 0
7 O 0
weeks O 0
of O 0
age O 0
, O 0
and O 0
weighing O 0
21 O 0
. O 0
0 O 0
to O 0
29 O 0
. O 0
1 O 0
g O 0
were O 0
randomly O 0
assigned O 0
to O 0
bupropion B-Chemical 0
HCl I-Chemical 0
120 O 0
mg O 0
/ O 0
kg O 0
treatment O 0
by O 0
intraperitoneal O 0
( O 0
IP O 0
) O 0
administration O 0
in O 0
7 O 0
groups O 0
( O 0
9 O 0
to O 0
10 O 0
animals O 0
per O 0
group O 0
) O 0
. O 0

Bupropion B-Chemical 0
HCl I-Chemical 0
was O 0
infused O 0
through O 0
a O 0
surgically O 0
implanted O 0
IP O 0
dosing O 0
catheter O 0
with O 0
infusions O 0
in O 0
each O 0
group O 0
of O 0
0 O 0
min O 0
, O 0
15 O 0
min O 0
, O 0
30 O 0
min O 0
, O 0
60 O 0
min O 0
, O 0
90 O 0
min O 0
, O 0
120 O 0
min O 0
, O 0
and O 0
240 O 0
min O 0
. O 0

The O 0
number O 0
, O 0
time O 0
of O 0
onset O 0
, O 0
duration O 0
and O 0
the O 0
intensity O 0
of O 0
the O 0
convulsions B-Disease 0
or O 0
absence O 0
of O 0
convulsions B-Disease 0
were O 0
recorded O 0
. O 0

RESULTS O 0
: O 0
The O 0
results O 0
showed O 0
that O 0
IP O 0
administration O 0
of O 0
bupropion B-Chemical 0
HCl I-Chemical 0
120 O 0
mg O 0
/ O 0
kg O 0
by O 0
bolus O 0
injection O 0
induced O 0
convulsions B-Disease 0
in O 0
6 O 0
out O 0
of O 0
10 O 0
mice O 0
( O 0
60 O 0
% O 0
of O 0
convulsing O 0
mice O 0
) O 0
in O 0
group O 0
1 O 0
. O 0

Logistic O 0
regression O 0
analysis O 0
revealed O 0
that O 0
infusion O 0
time O 0
was O 0
significant O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
0004 O 0
; O 0
odds O 0
ratio O 0
= O 0
0 O 0
. O 0
974 O 0
) O 0
and O 0
increasing O 0
the O 0
IP O 0
infusion O 0
time O 0
of O 0
bupropion B-Chemical 0
HCl I-Chemical 0
120 O 0
mg O 0
/ O 0
kg O 0
was O 0
associated O 0
with O 0
a O 0
91 O 0
% O 0
reduced O 0
odds O 0
of O 0
convulsions B-Disease 0
at O 0
infusion O 0
times O 0
of O 0
15 O 0
to O 0
90 O 0
min O 0
compared O 0
to O 0
bolus O 0
injection O 0
. O 0

Further O 0
increase O 0
in O 0
infusion O 0
time O 0
resulted O 0
in O 0
further O 0
reduction O 0
in O 0
the O 0
odds O 0
of O 0
convulsions B-Disease 0
to O 0
99 O 0
. O 0
8 O 0
% O 0
reduction O 0
at O 0
240 O 0
min O 0
. O 0

CONCLUSION O 0
: O 0
In O 0
conclusion O 0
, O 0
the O 0
demonstration O 0
of O 0
an O 0
inverse O 0
relationship O 0
between O 0
infusion O 0
time O 0
of O 0
a O 0
fixed O 0
and O 0
convulsive B-Disease 0
dose O 0
of O 0
bupropion B-Chemical 0
and O 0
the O 0
risk O 0
of O 0
convulsions B-Disease 0
in O 0
a O 0
prospective O 0
study O 0
is O 0
novel O 0
. O 0

Graft B-Disease 0
- I-Disease 0
versus I-Disease 0
- I-Disease 0
host I-Disease 0
disease I-Disease 0
prophylaxis O 0
with O 0
everolimus B-Chemical 0
and O 0
tacrolimus B-Chemical 0
is O 0
associated O 0
with O 0
a O 0
high O 0
incidence O 0
of O 0
sinusoidal B-Disease 0
obstruction I-Disease 0
syndrome I-Disease 0
and O 0
microangiopathy B-Disease 0
: O 0
results O 0
of O 0
the O 0
EVTAC O 0
trial O 0
. O 0

A O 0
calcineurin O 0
inhibitor O 0
combined O 0
with O 0
methotrexate B-Chemical 0
is O 0
the O 0
standard O 0
prophylaxis O 0
for O 0
graft B-Disease 0
- I-Disease 0
versus I-Disease 0
- I-Disease 0
host I-Disease 0
disease I-Disease 0
( O 0
GVHD B-Disease 0
) O 0
after O 0
allogeneic O 0
hematopoietic O 0
stem O 0
cell O 0
transplantation O 0
( O 0
HSCT O 0
) O 0
. O 0

Everolimus B-Chemical 0
, O 0
a O 0
derivative O 0
of O 0
sirolimus B-Chemical 0
, O 0
seems O 0
to O 0
mediate O 0
antileukemia O 0
effects O 0
. O 0

We O 0
report O 0
on O 0
a O 0
combination O 0
of O 0
everolimus B-Chemical 0
and O 0
tacrolimus B-Chemical 0
in O 0
24 O 0
patients O 0
( O 0
median O 0
age O 0
, O 0
62 O 0
years O 0
) O 0
with O 0
either O 0
myelodysplastic B-Disease 0
syndrome I-Disease 0
( O 0
MDS B-Disease 0
; O 0
n O 0
= O 0
17 O 0
) O 0
or O 0
acute B-Disease 0
myeloid I-Disease 0
leukemia I-Disease 0
( O 0
AML B-Disease 0
; O 0
n O 0
= O 0
7 O 0
) O 0
undergoing O 0
intensive O 0
conditioning O 0
followed O 0
by O 0
HSCT O 0
from O 0
related O 0
( O 0
n O 0
= O 0
4 O 0
) O 0
or O 0
unrelated O 0
( O 0
n O 0
= O 0
20 O 0
) O 0
donors O 0
. O 0

All O 0
patients O 0
engrafted O 0
, O 0
and O 0
only O 0
1 O 0
patient O 0
experienced O 0
grade O 0
IV O 0
mucositis B-Disease 0
. O 0

Nine O 0
patients O 0
( O 0
37 O 0
% O 0
) O 0
developed O 0
acute O 0
grade O 0
II O 0
- O 0
IV O 0
GVHD B-Disease 0
, O 0
and O 0
11 O 0
of O 0
17 O 0
evaluable O 0
patients O 0
( O 0
64 O 0
% O 0
) O 0
developed O 0
chronic O 0
extensive O 0
GVHD B-Disease 0
. O 0

Transplantation B-Disease 0
- I-Disease 0
associated I-Disease 0
microangiopathy I-Disease 0
( O 0
TMA B-Disease 0
) O 0
occurred O 0
in O 0
7 O 0
patients O 0
( O 0
29 O 0
% O 0
) O 0
, O 0
with O 0
2 O 0
cases O 0
of O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
. O 0

The O 0
study O 0
was O 0
terminated O 0
prematurely O 0
because O 0
an O 0
additional O 0
6 O 0
patients O 0
( O 0
25 O 0
% O 0
) O 0
developed O 0
sinusoidal B-Disease 0
obstruction I-Disease 0
syndrome I-Disease 0
( O 0
SOS B-Disease 0
) O 0
, O 0
which O 0
was O 0
fatal O 0
in O 0
2 O 0
cases O 0
. O 0

With O 0
a O 0
median O 0
follow O 0
- O 0
up O 0
of O 0
26 O 0
months O 0
, O 0
the O 0
2 O 0
- O 0
year O 0
overall O 0
survival O 0
rate O 0
was O 0
47 O 0
% O 0
. O 0

Although O 0
this O 0
new O 0
combination O 0
appears O 0
to O 0
be O 0
effective O 0
as O 0
a O 0
prophylactic O 0
regimen O 0
for O 0
acute O 0
GVHD B-Disease 0
, O 0
the O 0
incidence O 0
of O 0
TMA B-Disease 0
and O 0
SOS B-Disease 0
is O 0
considerably O 0
higher O 0
than O 0
seen O 0
with O 0
other O 0
regimens O 0
. O 0

Longitudinal O 0
assessment O 0
of O 0
air O 0
conduction O 0
audiograms O 0
in O 0
a O 0
phase O 0
III O 0
clinical O 0
trial O 0
of O 0
difluoromethylornithine B-Chemical 0
and O 0
sulindac B-Chemical 0
for O 0
prevention O 0
of O 0
sporadic O 0
colorectal B-Disease 0
adenomas I-Disease 0
. O 0

A O 0
phase O 0
III O 0
clinical O 0
trial O 0
assessed O 0
the O 0
recurrence O 0
of O 0
adenomatous B-Disease 0
polyps I-Disease 0
after O 0
treatment O 0
for O 0
36 O 0
months O 0
with O 0
difluoromethylornithine B-Chemical 0
( O 0
DFMO B-Chemical 0
) O 0
plus O 0
sulindac B-Chemical 0
or O 0
matched O 0
placebos O 0
. O 0

Temporary O 0
hearing B-Disease 0
loss I-Disease 0
is O 0
a O 0
known O 0
toxicity B-Disease 0
of O 0
treatment O 0
with O 0
DFMO B-Chemical 0
, O 0
thus O 0
a O 0
comprehensive O 0
approach O 0
was O 0
developed O 0
to O 0
analyze O 0
serial O 0
air O 0
conduction O 0
audiograms O 0
. O 0

The O 0
generalized O 0
estimating O 0
equation O 0
method O 0
estimated O 0
the O 0
mean O 0
difference O 0
between O 0
treatment O 0
arms O 0
with O 0
regard O 0
to O 0
change O 0
in O 0
air O 0
conduction O 0
pure O 0
tone O 0
thresholds O 0
while O 0
accounting O 0
for O 0
within O 0
- O 0
subject O 0
correlation O 0
due O 0
to O 0
repeated O 0
measurements O 0
at O 0
frequencies O 0
. O 0

Based O 0
on O 0
290 O 0
subjects O 0
, O 0
there O 0
was O 0
an O 0
average O 0
difference O 0
of O 0
0 O 0
. O 0
50 O 0
dB O 0
between O 0
subjects O 0
treated O 0
with O 0
DFMO B-Chemical 0
plus O 0
sulindac B-Chemical 0
compared O 0
with O 0
those O 0
treated O 0
with O 0
placebo O 0
( O 0
95 O 0
% O 0
confidence O 0
interval O 0
, O 0
- O 0
0 O 0
. O 0
64 O 0
to O 0
1 O 0
. O 0
63 O 0
dB O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
39 O 0
) O 0
, O 0
adjusted O 0
for O 0
baseline O 0
values O 0
, O 0
age O 0
, O 0
and O 0
frequencies O 0
. O 0

In O 0
the O 0
normal O 0
speech O 0
range O 0
of O 0
500 O 0
to O 0
3 O 0
, O 0
000 O 0
Hz O 0
, O 0
an O 0
estimated O 0
difference O 0
of O 0
0 O 0
. O 0
99 O 0
dB O 0
( O 0
- O 0
0 O 0
. O 0
17 O 0
to O 0
2 O 0
. O 0
14 O 0
dB O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
09 O 0
) O 0
was O 0
detected O 0
. O 0

Dose O 0
intensity O 0
did O 0
not O 0
add O 0
information O 0
to O 0
models O 0
. O 0

There O 0
were O 0
14 O 0
of O 0
151 O 0
( O 0
9 O 0
. O 0
3 O 0
% O 0
) O 0
in O 0
the O 0
DFMO B-Chemical 0
plus O 0
sulindac B-Chemical 0
group O 0
and O 0
4 O 0
of O 0
139 O 0
( O 0
2 O 0
. O 0
9 O 0
% O 0
) O 0
in O 0
the O 0
placebo O 0
group O 0
who O 0
experienced O 0
at O 0
least O 0
15 O 0
dB O 0
hearing O 0
reduction O 0
from O 0
baseline O 0
in O 0
2 O 0
or O 0
more O 0
consecutive O 0
frequencies O 0
across O 0
the O 0
entire O 0
range O 0
tested O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
02 O 0
) O 0
. O 0

Follow O 0
- O 0
up O 0
air O 0
conduction O 0
done O 0
at O 0
least O 0
6 O 0
months O 0
after O 0
end O 0
of O 0
treatment O 0
showed O 0
an O 0
adjusted O 0
mean O 0
difference O 0
in O 0
hearing O 0
thresholds O 0
of O 0
1 O 0
. O 0
08 O 0
dB O 0
( O 0
- O 0
0 O 0
. O 0
81 O 0
to O 0
2 O 0
. O 0
96 O 0
dB O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
26 O 0
) O 0
between O 0
treatment O 0
arms O 0
. O 0

There O 0
was O 0
no O 0
significant O 0
difference O 0
in O 0
the O 0
proportion O 0
of O 0
subjects O 0
in O 0
the O 0
DFMO B-Chemical 0
plus O 0
sulindac B-Chemical 0
group O 0
who O 0
experienced O 0
clinically O 0
significant O 0
hearing B-Disease 0
loss I-Disease 0
compared O 0
with O 0
the O 0
placebo O 0
group O 0
. O 0

The O 0
estimated O 0
attributable O 0
risk O 0
of O 0
ototoxicity B-Disease 0
from O 0
exposure O 0
to O 0
the O 0
drug O 0
is O 0
8 O 0
. O 0
4 O 0
% O 0
( O 0
95 O 0
% O 0
confidence O 0
interval O 0
, O 0
- O 0
2 O 0
. O 0
0 O 0
% O 0
to O 0
18 O 0
. O 0
8 O 0
% O 0
; O 0
P O 0
= O 0
0 O 0
. O 0
12 O 0
) O 0
. O 0

There O 0
is O 0
a O 0
< O 0
2 O 0
dB O 0
difference O 0
in O 0
mean O 0
threshold O 0
for O 0
patients O 0
treated O 0
with O 0
DFMO B-Chemical 0
plus O 0
sulindac B-Chemical 0
compared O 0
with O 0
those O 0
treated O 0
with O 0
placebo O 0
. O 0

Proteinase O 0
3 O 0
- O 0
antineutrophil O 0
cytoplasmic O 0
antibody O 0
- O 0
( O 0
PR3 O 0
- O 0
ANCA O 0
) O 0
positive O 0
necrotizing O 0
glomerulonephritis B-Disease 0
after O 0
restarting O 0
sulphasalazine B-Chemical 0
treatment O 0
. O 0

A O 0
59 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
ulcerative B-Disease 0
colitis I-Disease 0
developed O 0
red B-Disease 0
eyes I-Disease 0
, O 0
pleural B-Disease 0
effusion I-Disease 0
, O 0
eosinophilia B-Disease 0
and O 0
urinary B-Disease 0
abnormalities I-Disease 0
after O 0
restarting O 0
of O 0
sulphasalazine B-Chemical 0
treatment O 0
. O 0

Light O 0
microscopy O 0
of O 0
a O 0
kidney O 0
biopsy O 0
revealed O 0
segmental B-Disease 0
necrotizing I-Disease 0
glomerulonephritis I-Disease 0
without O 0
deposition O 0
of O 0
immunoglobulin O 0
or O 0
complement O 0
. O 0

Proteinase O 0
3 O 0
- O 0
antineutrophil O 0
cytoplasmic O 0
antibody O 0
( O 0
PR3 O 0
- O 0
ANCA O 0
) O 0
titer O 0
was O 0
elevated O 0
at O 0
183 O 0
ELISA O 0
units O 0
( O 0
EU O 0
) O 0
in O 0
sera O 0
( O 0
normal O 0
range O 0
less O 0
than O 0
10 O 0
EU O 0
) O 0
, O 0
myeloperoxidase O 0
- O 0
ANCA O 0
was O 0
negative O 0
. O 0

PR3 O 0
- O 0
ANCA O 0
titer O 0
was O 0
250 O 0
and O 0
1 O 0
, O 0
070 O 0
EU O 0
in O 0
pleural B-Disease 0
effusions I-Disease 0
on O 0
right O 0
and O 0
left O 0
side O 0
, O 0
respectively O 0
. O 0

Although O 0
cessation O 0
of O 0
sulphasalazine B-Chemical 0
treatment O 0
resulted O 0
in O 0
improvements O 0
in O 0
fever B-Disease 0
, O 0
red B-Disease 0
eyes I-Disease 0
, O 0
chest B-Disease 0
pain I-Disease 0
, O 0
titer O 0
of O 0
C O 0
- O 0
reactive O 0
protein O 0
and O 0
volume O 0
of O 0
the O 0
pleural B-Disease 0
effusions I-Disease 0
, O 0
we O 0
initiated O 0
steroid B-Chemical 0
therapy O 0
, O 0
because O 0
PR3 O 0
- O 0
ANCA O 0
titer O 0
rose O 0
to O 0
320 O 0
EU O 0
, O 0
eosinophil O 0
count O 0
increased O 0
to O 0
1 O 0
, O 0
100 O 0
cells O 0
/ O 0
microl O 0
, O 0
and O 0
the O 0
pleural B-Disease 0
effusion I-Disease 0
remained O 0
. O 0

One O 0
month O 0
after O 0
steroid B-Chemical 0
therapy O 0
, O 0
the O 0
pleural B-Disease 0
effusion I-Disease 0
disappeared O 0
, O 0
and O 0
PR3 O 0
- O 0
ANCA O 0
titer O 0
normalized O 0
3 O 0
months O 0
later O 0
. O 0

This O 0
case O 0
suggests O 0
that O 0
sulphasalazine B-Chemical 0
can O 0
induce O 0
PR3 O 0
- O 0
ANCA O 0
- O 0
positive O 0
necrotizing O 0
glomerulonephritis B-Disease 0
. O 0

Comparison O 0
of O 0
unilateral O 0
pallidotomy O 0
and O 0
subthalamotomy O 0
findings O 0
in O 0
advanced O 0
idiopathic B-Disease 0
Parkinson I-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

A O 0
prospective O 0
, O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
pilot O 0
study O 0
to O 0
compare O 0
the O 0
results O 0
of O 0
stereotactic O 0
unilateral O 0
pallidotomy O 0
and O 0
subthalamotomy O 0
in O 0
advanced O 0
idiopathic B-Disease 0
Parkinson I-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
( O 0
PD B-Disease 0
) O 0
refractory O 0
to O 0
medical O 0
treatment O 0
was O 0
designed O 0
. O 0

Ten O 0
consecutive O 0
patients O 0
( O 0
mean O 0
age O 0
, O 0
58 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
6 O 0
. O 0
8 O 0
years O 0
; O 0
7 O 0
men O 0
, O 0
3 O 0
women O 0
) O 0
with O 0
similar O 0
characteristics O 0
at O 0
the O 0
duration O 0
of O 0
disease O 0
( O 0
mean O 0
disease O 0
time O 0
, O 0
8 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
5 O 0
years O 0
) O 0
, O 0
disabling O 0
motor O 0
fluctuations O 0
( O 0
Hoehn O 0
_ O 0
Yahr O 0
stage O 0
3 O 0
- O 0
5 O 0
in O 0
off O 0
- O 0
drug O 0
phases O 0
) O 0
and O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
were O 0
selected O 0
. O 0

All O 0
patients O 0
had O 0
bilateral O 0
symptoms O 0
and O 0
their O 0
levodopa B-Chemical 0
equivalent O 0
dosing O 0
were O 0
analysed O 0
. O 0

Six O 0
patients O 0
were O 0
operated O 0
on O 0
in O 0
the O 0
globus O 0
pallidus O 0
interna O 0
( O 0
GPi O 0
) O 0
and O 0
four O 0
in O 0
the O 0
subthalamic O 0
nucleus O 0
( O 0
STN O 0
) O 0
. O 0

Clinical O 0
evaluation O 0
included O 0
the O 0
use O 0
of 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
( O 0
UPDRS O 0
) O 0
, O 0
Hoehn O 0
_ O 0
Yahr O 0
score O 0
and O 0
Schwab O 0
England O 0
activities O 0
of O 0
daily O 0
living O 0
( O 0
ADL O 0
) O 0
score O 0
in O 0
' O 0
on O 0
' O 0
- O 0
and O 0
' O 0
off O 0
' O 0
- O 0
drug O 0
conditions O 0
before O 0
surgery O 0
and O 0
6 O 0
months O 0
after O 0
surgery O 0
. O 0

There O 0
was O 0
statistically O 0
significant O 0
improvement O 0
in O 0
all O 0
contralateral O 0
major O 0
parkinsonian B-Disease 0
motor O 0
signs O 0
in O 0
all O 0
patients O 0
followed O 0
for O 0
6 O 0
months O 0
. O 0

Levodopa B-Chemical 0
equivalent O 0
daily O 0
intake O 0
was O 0
significantly O 0
reduced O 0
in O 0
the O 0
STN O 0
group O 0
. O 0

Changes O 0
in O 0
UPDRS O 0
, O 0
Hoehn O 0
_ O 0
Yahr O 0
and O 0
Schwab O 0
England O 0
ADL O 0
scores O 0
were O 0
similar O 0
in O 0
both O 0
groups O 0
. O 0

Cognitive O 0
functions O 0
were O 0
unchanged O 0
in O 0
both O 0
groups O 0
. O 0

Complications O 0
were O 0
observed O 0
in O 0
two O 0
patients O 0
: O 0
one O 0
had O 0
a O 0
left O 0
homonymous B-Disease 0
hemianopsia I-Disease 0
after O 0
pallidotomy O 0
and O 0
another O 0
one O 0
developed O 0
left O 0
hemiballistic O 0
movements O 0
3 O 0
days O 0
after O 0
subthalamotomy O 0
which O 0
partly O 0
improved O 0
within O 0
1 O 0
month O 0
with O 0
Valproate B-Chemical 0
1000 O 0
mg O 0
/ O 0
day O 0
. O 0

The O 0
findings O 0
of O 0
this O 0
study O 0
suggest O 0
that O 0
lesions O 0
of O 0
the O 0
unilateral O 0
STN O 0
and O 0
GPi O 0
are O 0
equally O 0
effective O 0
treatment O 0
for O 0
patients O 0
with O 0
advanced O 0
PD B-Disease 0
refractory O 0
to O 0
medical O 0
treatment O 0
. O 0

DSMM O 0
XI O 0
study O 0
: O 0
dose O 0
definition O 0
for O 0
intravenous O 0
cyclophosphamide B-Chemical 0
in O 0
combination O 0
with O 0
bortezomib B-Chemical 0
/ O 0
dexamethasone B-Chemical 0
for O 0
remission O 0
induction O 0
in O 0
patients O 0
with O 0
newly O 0
diagnosed O 0
myeloma B-Disease 0
. O 0

A O 0
clinical O 0
trial O 0
was O 0
initiated O 0
to O 0
evaluate O 0
the O 0
recommended O 0
dose O 0
of O 0
cyclophosphamide B-Chemical 0
in O 0
combination O 0
with O 0
bortezomib B-Chemical 0
and O 0
dexamethasone B-Chemical 0
as O 0
induction O 0
treatment O 0
before O 0
stem O 0
cell O 0
transplantation O 0
for O 0
younger O 0
patients O 0
with O 0
newly O 0
diagnosed O 0
multiple B-Disease 0
myeloma I-Disease 0
( O 0
MM B-Disease 0
) O 0
. O 0

Thirty O 0
patients O 0
were O 0
treated O 0
with O 0
three O 0
21 O 0
- O 0
day O 0
cycles O 0
of O 0
bortezomib B-Chemical 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
plus O 0
dexamethasone B-Chemical 0
40 O 0
mg O 0
on O 0
the O 0
day O 0
of O 0
bortezomib B-Chemical 0
injection O 0
and O 0
the O 0
day O 0
after O 0
plus O 0
cyclophosphamide B-Chemical 0
at O 0
900 O 0
, O 0
1 O 0
, O 0
200 O 0
, O 0
or O 0
1 O 0
, O 0
500 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
on O 0
day O 0
1 O 0
. O 0

The O 0
maximum O 0
tolerated O 0
dose O 0
of O 0
cyclophosphamide B-Chemical 0
was O 0
defined O 0
as O 0
900 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
. O 0

At O 0
this O 0
dose O 0
level O 0
, O 0
92 O 0
% O 0
of O 0
patients O 0
achieved O 0
at O 0
least O 0
a O 0
partial O 0
response O 0
. O 0

The O 0
overall O 0
response O 0
rate O 0
[ O 0
complete O 0
response O 0
( O 0
CR O 0
) O 0
plus O 0
partial O 0
response O 0
( O 0
PR O 0
) O 0
] O 0
across O 0
all O 0
dose O 0
levels O 0
was O 0
77 O 0
% O 0
, O 0
with O 0
a O 0
10 O 0
% O 0
CR O 0
rate O 0
. O 0

No O 0
patient O 0
experienced O 0
progressive O 0
disease O 0
. O 0

The O 0
most O 0
frequent O 0
adverse O 0
events O 0
were O 0
hematological B-Disease 0
and I-Disease 0
gastrointestinal I-Disease 0
toxicities I-Disease 0
as O 0
well O 0
as O 0
neuropathy B-Disease 0
. O 0

The O 0
results O 0
suggest O 0
that O 0
bortezomib B-Chemical 0
in O 0
combination O 0
with O 0
cyclophosphamide B-Chemical 0
at O 0
900 O 0
mg O 0
/ O 0
m O 0
( O 0
2 O 0
) O 0
and O 0
dexamethasone B-Chemical 0
is O 0
an O 0
effective O 0
induction O 0
treatment O 0
for O 0
patients O 0
with O 0
newly O 0
diagnosed O 0
MM B-Disease 0
that O 0
warrants O 0
further O 0
investigation O 0
. O 0

Naloxone B-Chemical 0
reversal O 0
of O 0
hypotension B-Disease 0
due O 0
to O 0
captopril B-Chemical 0
overdose B-Disease 0
. O 0

The O 0
hemodynamic O 0
effects O 0
of O 0
captopril B-Chemical 0
and O 0
other O 0
angiotensin B-Chemical 0
- I-Chemical 0
converting I-Chemical 0
enzyme I-Chemical 0
inhibitors I-Chemical 0
may O 0
be O 0
mediated O 0
by O 0
the O 0
endogenous O 0
opioid O 0
system O 0
. O 0

The O 0
opioid O 0
antagonist O 0
naloxone B-Chemical 0
has O 0
been O 0
shown O 0
to O 0
block O 0
or O 0
reverse O 0
the O 0
hypotensive B-Disease 0
actions O 0
of O 0
captopril B-Chemical 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
an O 0
intentional O 0
captopril B-Chemical 0
overdose B-Disease 0
, O 0
manifested O 0
by O 0
marked O 0
hypotension B-Disease 0
, O 0
that O 0
resolved O 0
promptly O 0
with O 0
the O 0
administration O 0
of O 0
naloxone B-Chemical 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
reported O 0
case O 0
of O 0
captopril B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
treated O 0
with O 0
naloxone B-Chemical 0
. O 0

Our O 0
experience O 0
demonstrates O 0
a O 0
possible O 0
role O 0
of O 0
naloxone B-Chemical 0
in O 0
the O 0
reversal O 0
of O 0
hypotension B-Disease 0
resulting O 0
from O 0
captopril B-Chemical 0
. O 0

Identification O 0
of O 0
a O 0
simple O 0
and O 0
sensitive O 0
microplate O 0
method O 0
for O 0
the O 0
detection O 0
of O 0
oversulfated O 0
chondroitin B-Chemical 0
sulfate I-Chemical 0
in O 0
heparin B-Chemical 0
products O 0
. O 0

Heparin B-Chemical 0
is O 0
a O 0
commonly O 0
implemented O 0
anticoagulant O 0
used O 0
to O 0
treat O 0
critically O 0
ill O 0
patients O 0
. O 0

Recently O 0
, O 0
a O 0
number O 0
of O 0
commercial O 0
lots O 0
of O 0
heparin B-Chemical 0
products O 0
were O 0
found O 0
to O 0
be O 0
contaminated O 0
with O 0
an O 0
oversulfated O 0
chondroitin B-Chemical 0
sulfate I-Chemical 0
( O 0
OSCS O 0
) O 0
derivative O 0
that O 0
could O 0
elicit O 0
a O 0
hypotensive B-Disease 0
response O 0
in O 0
pigs O 0
following O 0
a O 0
single O 0
high O 0
- O 0
dose O 0
infusion O 0
. O 0

Using O 0
both O 0
contaminated O 0
heparin B-Chemical 0
products O 0
and O 0
the O 0
synthetically O 0
produced O 0
derivative O 0
, O 0
we O 0
showed O 0
that O 0
the O 0
OSCS O 0
produces O 0
dose O 0
- O 0
dependent O 0
hypotension B-Disease 0
in O 0
pigs O 0
. O 0

The O 0
no O 0
observed O 0
effect O 0
level O 0
( O 0
NOEL O 0
) O 0
for O 0
this O 0
contaminant O 0
appears O 0
to O 0
be O 0
approximately O 0
1mg O 0
/ O 0
kg O 0
, O 0
corresponding O 0
to O 0
a O 0
contamination O 0
level O 0
of O 0
approximately O 0
3 O 0
% O 0
. O 0

We O 0
also O 0
demonstrated O 0
that O 0
OSCS O 0
can O 0
be O 0
identified O 0
in O 0
heparin B-Chemical 0
products O 0
using O 0
a O 0
simple O 0
, O 0
inexpensive O 0
, O 0
commercially O 0
available O 0
heparin B-Chemical 0
enzyme O 0
immunoassay O 0
( O 0
EIA O 0
) O 0
kit O 0
that O 0
has O 0
a O 0
limit O 0
of O 0
detection O 0
of O 0
approximately O 0
0 O 0
. O 0
1 O 0
% O 0
, O 0
well O 0
below O 0
the O 0
NOEL O 0
. O 0

This O 0
kit O 0
may O 0
provide O 0
a O 0
useful O 0
method O 0
to O 0
test O 0
heparin B-Chemical 0
products O 0
for O 0
contamination O 0
with O 0
oversulfated O 0
GAG O 0
derivatives O 0
. O 0

5 B-Chemical 0
flourouracil I-Chemical 0
- O 0
induced O 0
apical B-Disease 0
ballooning I-Disease 0
syndrome I-Disease 0
: O 0
a O 0
case O 0
report O 0
. O 0

The O 0
apical B-Disease 0
ballooning I-Disease 0
syndrome I-Disease 0
( O 0
ABS B-Disease 0
) O 0
is O 0
a O 0
recently O 0
described O 0
stress O 0
- O 0
mediated O 0
acute B-Disease 0
cardiac I-Disease 0
syndrome I-Disease 0
characterized O 0
by O 0
transient O 0
wall O 0
- O 0
motion O 0
abnormalities O 0
involving O 0
the O 0
apex O 0
and O 0
midventricle O 0
with O 0
hyperkinesis B-Disease 0
of O 0
the O 0
basal O 0
left O 0
ventricular O 0
( O 0
LV O 0
) O 0
segments O 0
without O 0
obstructive O 0
epicardial B-Disease 0
coronary I-Disease 0
disease I-Disease 0
. O 0

Cardiotoxicity B-Disease 0
is O 0
not O 0
an O 0
uncommon O 0
adverse O 0
effect O 0
of O 0
chemotherapeutic O 0
agents O 0
. O 0

However O 0
, O 0
there O 0
are O 0
no O 0
reports O 0
of O 0
ABS B-Disease 0
secondary O 0
to O 0
chemotherapeutic O 0
agents O 0
. O 0

We O 0
describe O 0
the O 0
case O 0
of O 0
a O 0
woman O 0
who O 0
developed O 0
the O 0
syndrome O 0
after O 0
chemotherapy O 0
for O 0
metastatic O 0
cancer B-Disease 0
. O 0

A O 0
79 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
presented O 0
with O 0
typical O 0
ischemic B-Disease 0
chest B-Disease 0
pain I-Disease 0
, O 0
elevated O 0
cardiac O 0
enzymes O 0
with O 0
significant O 0
ST O 0
- O 0
segment O 0
abnormalities O 0
on O 0
her O 0
electrocardiogram O 0
. O 0

She O 0
underwent O 0
recent O 0
chemotherapy O 0
with O 0
fluorouracil B-Chemical 0
for O 0
metastatic O 0
colorectal B-Disease 0
cancer I-Disease 0
. O 0

Echocardiography O 0
revealed O 0
a O 0
wall O 0
- O 0
motion O 0
abnormality O 0
involving O 0
the O 0
apical O 0
and O 0
periapical O 0
segments O 0
which O 0
appeared O 0
akinetic B-Disease 0
. O 0

Coronary O 0
angiography O 0
revealed O 0
no O 0
obstructive O 0
coronary O 0
lesions O 0
. O 0

The O 0
patient O 0
was O 0
stabilized O 0
with O 0
medical O 0
therapy O 0
. O 0

Four O 0
weeks O 0
later O 0
she O 0
remained O 0
completely O 0
asymptomatic O 0
. O 0

Echocardiogram O 0
revealed O 0
a O 0
normal O 0
ejection O 0
fraction O 0
and O 0
a O 0
resolution O 0
of O 0
the O 0
apical O 0
akinesis B-Disease 0
. O 0

Pathogenetic O 0
mechanisms O 0
of O 0
cardiac B-Disease 0
complications I-Disease 0
in O 0
cancer B-Disease 0
patients O 0
undergoing O 0
chemotherapy O 0
include O 0
coronary B-Disease 0
vasospasm I-Disease 0
, O 0
endothelial O 0
damage O 0
and O 0
consequent O 0
thrombus B-Disease 0
formation O 0
. O 0

In O 0
our O 0
patient O 0
, O 0
both O 0
supraphysiologic O 0
levels O 0
of O 0
plasma O 0
catecholamines B-Chemical 0
and O 0
stress O 0
related O 0
neuropeptides O 0
caused O 0
by O 0
cancer B-Disease 0
diagnosis O 0
as O 0
well O 0
as O 0
chemotherapy O 0
may O 0
have O 0
contributed O 0
the O 0
development O 0
of O 0
ABS B-Disease 0
. O 0

Rapid O 0
reversal O 0
of O 0
anticoagulation O 0
reduces O 0
hemorrhage B-Disease 0
volume O 0
in O 0
a O 0
mouse O 0
model O 0
of O 0
warfarin B-Chemical 0
- O 0
associated O 0
intracerebral B-Disease 0
hemorrhage I-Disease 0
. O 0

Warfarin B-Chemical 0
- O 0
associated O 0
intracerebral B-Disease 0
hemorrhage I-Disease 0
( O 0
W O 0
- O 0
ICH B-Disease 0
) O 0
is O 0
a O 0
severe O 0
type O 0
of O 0
stroke B-Disease 0
. O 0

There O 0
is O 0
no O 0
consensus O 0
on O 0
the O 0
optimal O 0
treatment O 0
for O 0
W O 0
- O 0
ICH B-Disease 0
. O 0

Using O 0
a O 0
mouse O 0
model O 0
, O 0
we O 0
tested O 0
whether O 0
the O 0
rapid O 0
reversal O 0
of O 0
anticoagulation O 0
using O 0
human O 0
prothrombin B-Chemical 0
complex I-Chemical 0
concentrate I-Chemical 0
( O 0
PCC B-Chemical 0
) O 0
can O 0
reduce O 0
hemorrhagic O 0
blood O 0
volume O 0
. O 0

Male O 0
CD O 0
- O 0
1 O 0
mice O 0
were O 0
treated O 0
with O 0
warfarin B-Chemical 0
( O 0
2 O 0
mg O 0
/ O 0
kg O 0
over O 0
24 O 0
h O 0
) O 0
, O 0
resulting O 0
in O 0
a O 0
mean O 0
( O 0
+ O 0
/ O 0
- O 0
s O 0
. O 0
d O 0
. O 0
) O 0
International O 0
Normalized O 0
Ratio O 0
of O 0
3 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
9 O 0
. O 0

First O 0
, O 0
we O 0
showed O 0
that O 0
an O 0
intravenous O 0
administration O 0
of O 0
human O 0
PCC B-Chemical 0
rapidly O 0
reversed O 0
anticoagulation O 0
in O 0
mice O 0
. O 0

Second O 0
, O 0
a O 0
stereotactic O 0
injection O 0
of O 0
collagenase O 0
was O 0
administered O 0
to O 0
induce O 0
hemorrhage B-Disease 0
in O 0
the O 0
right O 0
striatum O 0
. O 0

Forty O 0
- O 0
five O 0
minutes O 0
later O 0
, O 0
the O 0
animals O 0
were O 0
randomly O 0
treated O 0
with O 0
PCC B-Chemical 0
( O 0
100 O 0
U O 0
/ O 0
kg O 0
) O 0
or O 0
saline O 0
i O 0
. O 0
v O 0
. O 0
( O 0
n O 0
= O 0
12 O 0
per O 0
group O 0
) O 0
. O 0

Twenty O 0
- O 0
four O 0
hours O 0
after O 0
hemorrhage B-Disease 0
induction O 0
, O 0
hemorrhagic O 0
blood O 0
volume O 0
was O 0
quantified O 0
using O 0
a O 0
photometric O 0
hemoglobin O 0
assay O 0
. O 0

The O 0
mean O 0
hemorrhagic O 0
blood O 0
volume O 0
was O 0
reduced O 0
in O 0
PCC B-Chemical 0
- O 0
treated O 0
animals O 0
( O 0
6 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
1 O 0
microL O 0
) O 0
compared O 0
with O 0
saline O 0
controls O 0
( O 0
15 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
11 O 0
. O 0
2 O 0
microL O 0
, O 0
P O 0
= O 0
0 O 0
. O 0
015 O 0
) O 0
. O 0

In O 0
the O 0
saline O 0
group O 0
, O 0
45 O 0
% O 0
of O 0
the O 0
mice O 0
developed O 0
large O 0
hematomas B-Disease 0
( O 0
i O 0
. O 0
e O 0
. O 0
, O 0
> O 0
15 O 0
microL O 0
) O 0
. O 0

In O 0
contrast O 0
, O 0
such O 0
extensive O 0
lesions O 0
were O 0
never O 0
found O 0
in O 0
the O 0
PCC B-Chemical 0
group O 0
. O 0

We O 0
provide O 0
experimental O 0
data O 0
suggesting O 0
PCC B-Chemical 0
to O 0
be O 0
an O 0
effective O 0
acute O 0
treatment O 0
for O 0
W O 0
- O 0
ICH B-Disease 0
in O 0
terms O 0
of O 0
reducing O 0
hemorrhagic O 0
blood O 0
volume O 0
. O 0

Future O 0
studies O 0
are O 0
needed O 0
to O 0
assess O 0
the O 0
therapeutic O 0
potential O 0
emerging O 0
from O 0
our O 0
finding O 0
for O 0
human O 0
W O 0
- O 0
ICH B-Disease 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 O 0
symptoms O 0
and 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
. O 0

This O 0
is O 0
an O 0
updated O 0
version O 0
of O 0
the O 0
original O 0
Cochrane O 0
review O 0
first O 0
published O 0
in O 0
2005 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
cardiovascular O 0
outcomes O 0
, O 0
cancer B-Disease 0
, O 0
gallbladder B-Disease 0
disease I-Disease 0
, O 0
cognition O 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
to O 0
November O 0
2007 O 0
: O 0
Trials O 0
Register O 0
of O 0
the O 0
Cochrane O 0
Menstrual B-Disease 0
Disorders I-Disease 0
and O 0
Subfertility O 0
Group O 0
, O 0
Cochrane O 0
Central O 0
Register O 0
of O 0
Controlled O 0
Trials O 0
, O 0
MEDLINE O 0
, O 0
EMBASE O 0
, O 0
Biological O 0
Abstracts O 0
. O 0

Also 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
. 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
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

HT O 0
included O 0
oestrogens B-Chemical 0
, O 0
with O 0
or O 0
without O 0
progestogens B-Chemical 0
, O 0
via O 0
oral O 0
, O 0
transdermal O 0
, O 0
subcutaneous O 0
or O 0
transnasal O 0
routes O 0
. O 0

DATA O 0
COLLECTION O 0
AND O 0
ANALYSIS O 0
: O 0
Two O 0
authors O 0
independently O 0
assessed O 0
trial O 0
quality O 0
and O 0
extracted O 0
data O 0
. O 0

MAIN O 0
RESULTS O 0
: O 0
Nineteen O 0
trials O 0
involving O 0
41 O 0
, O 0
904 O 0
women O 0
were O 0
included 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
thrombo I-Disease 0
- I-Disease 0
embolism 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
three O 0
years O 0
) O 0
, O 0
breast B-Disease 0
cancer I-Disease 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
significantly O 0
increased O 0
the O 0
risk O 0
of O 0
venous B-Disease 0
thrombo I-Disease 0
- I-Disease 0
embolism I-Disease 0
, O 0
stroke B-Disease 0
and O 0
gallbladder B-Disease 0
disease I-Disease 0
( O 0
after O 0
one O 0
to O 0
two O 0
years O 0
, O 0
three O 0
years O 0
and O 0
seven O 0
years O 0
' O 0
use O 0
respectively O 0
) O 0
, O 0
but O 0
did O 0
not O 0
significantly O 0
increase O 0
the O 0
risk O 0
of O 0
breast B-Disease 0
cancer I-Disease 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
( O 0
for O 0
combined O 0
HT O 0
) O 0
colon B-Disease 0
cancer I-Disease 0
, O 0
with O 0
long O 0
- O 0
term O 0
use O 0
. O 0

Among O 0
women O 0
aged O 0
over O 0
65 O 0
who O 0
were O 0
relatively O 0
healthy O 0
( O 0
i O 0
. O 0
e O 0
. O 0
generally O 0
fit O 0
, O 0
without O 0
overt O 0
disease O 0
) O 0
and 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
thrombo I-Disease 0
- I-Disease 0
embolism I-Disease 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
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
thrombo I-Disease 0
- I-Disease 0
embolism 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
low O 0
, O 0
at O 0
less O 0
than O 0
1 O 0
/ O 0
500 O 0
. O 0

However O 0
, O 0
this O 0
study O 0
was O 0
not O 0
powered O 0
to O 0
detect O 0
differences O 0
between O 0
groups O 0
of O 0
younger O 0
women 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 O 0
disease O 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

Acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
in O 0
patients O 0
with O 0
AIDS B-Disease 0
on O 0
tenofovir B-Chemical 0
while O 0
receiving O 0
prolonged O 0
vancomycin B-Chemical 0
course O 0
for O 0
osteomyelitis B-Disease 0
. O 0

Renal B-Disease 0
failure I-Disease 0
developed O 0
after O 0
a O 0
prolonged O 0
course O 0
of O 0
vancomycin B-Chemical 0
therapy O 0
in O 0
2 O 0
patients O 0
who O 0
were O 0
receiving O 0
tenofovir B-Chemical 0
disoproxil I-Chemical 0
fumarate I-Chemical 0
as O 0
part O 0
of O 0
an O 0
antiretroviral O 0
regimen O 0
. O 0

Tenofovir B-Chemical 0
has O 0
been O 0
implicated O 0
in O 0
the O 0
development O 0
of O 0
Fanconi B-Disease 0
syndrome I-Disease 0
and O 0
renal B-Disease 0
insufficiency I-Disease 0
because O 0
of O 0
its O 0
effects O 0
on O 0
the O 0
proximal O 0
renal O 0
tubule O 0
. O 0

Vancomycin B-Chemical 0
nephrotoxicity B-Disease 0
is O 0
infrequent O 0
but O 0
may O 0
result O 0
from O 0
coadministration O 0
with O 0
a O 0
nephrotoxic B-Disease 0
agent O 0
. O 0

Clinicians O 0
should O 0
be O 0
aware O 0
that O 0
tenofovir B-Chemical 0
may O 0
raise O 0
the O 0
risk O 0
of O 0
renal B-Disease 0
failure I-Disease 0
during O 0
prolonged O 0
administration O 0
of O 0
vancomycin B-Chemical 0
. O 0

Recurrent O 0
dysosmia B-Disease 0
induced O 0
by O 0
pyrazinamide B-Chemical 0
. O 0

Pyrazinamide B-Chemical 0
can O 0
have O 0
adverse O 0
effects O 0
such O 0
as O 0
hepatic B-Disease 0
toxicity I-Disease 0
, O 0
hyperuricemia B-Disease 0
or O 0
digestive O 0
disorders O 0
. O 0

In O 0
rare O 0
cases O 0
, O 0
alterations O 0
in O 0
taste O 0
and O 0
smell O 0
function O 0
have O 0
been O 0
reported O 0
for O 0
pyrazinamide B-Chemical 0
when O 0
combined O 0
with O 0
other O 0
drugs O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
reversible O 0
olfactory B-Disease 0
disorder I-Disease 0
related O 0
to O 0
pyrazinamide B-Chemical 0
in O 0
a O 0
woman O 0
, O 0
with O 0
a O 0
positive O 0
rechallenge O 0
. O 0

The O 0
patient O 0
presented O 0
every O 0
day O 0
a O 0
sensation O 0
of O 0
smelling O 0
something O 0
burning O 0
15 O 0
min O 0
after O 0
drug O 0
intake O 0
. O 0

Dysosmia B-Disease 0
disappeared O 0
completely O 0
after O 0
pyrazinamide B-Chemical 0
withdrawal O 0
and O 0
recurred O 0
after O 0
its O 0
rechallenge O 0
. O 0

The O 0
case O 0
was O 0
reported O 0
to O 0
the O 0
Tunisian O 0
Centre O 0
of O 0
Pharmacovigilance O 0
. O 0

Mice O 0
lacking O 0
mPGES O 0
- O 0
1 O 0
are O 0
resistant O 0
to O 0
lithium B-Chemical 0
- O 0
induced O 0
polyuria B-Disease 0
. O 0

Cyclooxygenase O 0
- O 0
2 O 0
activity O 0
is O 0
required O 0
for O 0
the O 0
development O 0
of O 0
lithium B-Chemical 0
- O 0
induced O 0
polyuria B-Disease 0
. O 0

However O 0
, O 0
the O 0
involvement O 0
of O 0
a O 0
specific O 0
, O 0
terminal O 0
prostaglandin B-Chemical 0
( O 0
PG B-Chemical 0
) O 0
isomerase O 0
has O 0
not O 0
been O 0
evaluated O 0
. O 0

The O 0
present O 0
study O 0
was O 0
undertaken O 0
to O 0
assess O 0
lithium B-Chemical 0
- O 0
induced O 0
polyuria B-Disease 0
in O 0
mice O 0
deficient O 0
in O 0
microsomal O 0
prostaglandin B-Chemical 0
E I-Chemical 0
synthase O 0
- O 0
1 O 0
( O 0
mPGES O 0
- O 0
1 O 0
) O 0
. O 0

A O 0
2 O 0
- O 0
wk O 0
administration O 0
of O 0
LiCl B-Chemical 0
( O 0
4 O 0
mmol O 0
. O 0
kg O 0
( O 0
- O 0
1 O 0
) O 0
. O 0
day O 0
( O 0
- O 0
1 O 0
) O 0
ip O 0
) O 0
in O 0
mPGES O 0
- O 0
1 O 0
+ O 0
/ O 0
+ O 0
mice O 0
led O 0
to O 0
a O 0
marked O 0
polyuria B-Disease 0
with O 0
hyposmotic O 0
urine O 0
. O 0

This O 0
was O 0
associated O 0
with O 0
elevated O 0
renal O 0
mPGES O 0
- O 0
1 O 0
protein O 0
expression O 0
and O 0
increased O 0
urine O 0
PGE B-Chemical 0
( I-Chemical 0
2 I-Chemical 0
) I-Chemical 0
excretion O 0
. O 0

In O 0
contrast O 0
, O 0
mPGES O 0
- O 0
1 O 0
- O 0
/ O 0
- O 0
mice O 0
were O 0
largely O 0
resistant O 0
to O 0
lithium B-Chemical 0
- O 0
induced O 0
polyuria B-Disease 0
and O 0
a O 0
urine O 0
concentrating O 0
defect O 0
, O 0
accompanied O 0
by O 0
nearly O 0
complete O 0
blockade O 0
of O 0
high O 0
urine O 0
PGE B-Chemical 0
( I-Chemical 0
2 I-Chemical 0
) I-Chemical 0
and O 0
cAMP O 0
output O 0
. O 0

Immunoblotting O 0
, O 0
immunohistochemistry O 0
, O 0
and O 0
quantitative O 0
( O 0
q O 0
) O 0
RT O 0
- O 0
PCR O 0
consistently O 0
detected O 0
a O 0
significant O 0
decrease O 0
in O 0
aquaporin O 0
- O 0
2 O 0
( O 0
AQP2 O 0
) O 0
protein O 0
expression O 0
in O 0
both O 0
the O 0
renal O 0
cortex O 0
and O 0
medulla O 0
of O 0
lithium B-Chemical 0
- O 0
treated O 0
+ O 0
/ O 0
+ O 0
mice O 0
. O 0

This O 0
decrease O 0
was O 0
significantly O 0
attenuated O 0
in O 0
the O 0
- O 0
/ O 0
- O 0
mice O 0
. O 0

qRT O 0
- O 0
PCR O 0
detected O 0
similar O 0
patterns O 0
of O 0
changes O 0
in O 0
AQP2 O 0
mRNA O 0
in O 0
the O 0
medulla O 0
but O 0
not O 0
in O 0
the O 0
cortex O 0
. O 0

Similarly O 0
, O 0
the O 0
total O 0
protein O 0
abundance O 0
of O 0
the O 0
Na B-Chemical 0
- O 0
K B-Chemical 0
- O 0
2Cl B-Chemical 0
cotransporter O 0
( O 0
NKCC2 O 0
) O 0
in O 0
the O 0
medulla O 0
but O 0
not O 0
in O 0
the O 0
cortex O 0
of O 0
the O 0
+ O 0
/ O 0
+ O 0
mice O 0
was O 0
significantly O 0
reduced O 0
by O 0
lithium B-Chemical 0
treatment O 0
. O 0

In O 0
contrast O 0
, O 0
the O 0
dowregulation O 0
of O 0
renal O 0
medullary O 0
NKCC2 O 0
expression O 0
was O 0
significantly O 0
attenuated O 0
in O 0
the O 0
- O 0
/ O 0
- O 0
mice O 0
. O 0

We O 0
conclude O 0
that O 0
mPGES O 0
- O 0
1 O 0
- O 0
derived O 0
PGE B-Chemical 0
( I-Chemical 0
2 I-Chemical 0
) I-Chemical 0
mediates O 0
lithium B-Chemical 0
- O 0
induced O 0
polyuria B-Disease 0
likely O 0
via O 0
inhibition O 0
of O 0
AQP2 O 0
and O 0
NKCC2 O 0
expression O 0
. O 0

Preservation O 0
of O 0
renal O 0
blood O 0
flow O 0
during O 0
hypotension B-Disease 0
induced O 0
with O 0
fenoldopam B-Chemical 0
in O 0
dogs O 0
. O 0

The O 0
introduction O 0
of O 0
drugs O 0
that O 0
could O 0
induce O 0
hypotension B-Disease 0
with O 0
different O 0
pharmacological O 0
actions O 0
would O 0
be O 0
advantageous O 0
because O 0
side O 0
effects O 0
unique O 0
to O 0
a O 0
specific O 0
drug O 0
could O 0
be O 0
minimized O 0
by O 0
selecting O 0
appropriate O 0
therapy O 0
. O 0

Specific O 0
dopamine B-Chemical 0
- O 0
1 O 0
, O 0
( O 0
DA1 B-Chemical 0
) O 0
and O 0
dopamine B-Chemical 0
- O 0
2 O 0
( O 0
DA2 B-Chemical 0
) O 0
receptor O 0
agonists O 0
are O 0
now O 0
under O 0
clinical O 0
investigation O 0
. O 0

Fenoldopam B-Chemical 0
mesylate I-Chemical 0
is O 0
a O 0
specific O 0
DA1 O 0
receptor O 0
agonist O 0
that O 0
lowers O 0
blood O 0
pressure O 0
by O 0
vasodilatation O 0
. O 0

The O 0
hypothesis O 0
that O 0
fenoldopam B-Chemical 0
could O 0
be O 0
used O 0
to O 0
induce O 0
hypotension B-Disease 0
and O 0
preserve O 0
blood O 0
flow O 0
to O 0
the O 0
kidney O 0
was O 0
tested O 0
. O 0

Systemic O 0
aortic O 0
blood O 0
pressure O 0
and O 0
renal O 0
blood O 0
flow O 0
were O 0
measured O 0
continuously O 0
with O 0
a O 0
carotid O 0
arterial O 0
catheter O 0
and O 0
an O 0
electromagnetic O 0
flow O 0
probe O 0
respectively O 0
, O 0
in O 0
order O 0
to O 0
compare O 0
the O 0
cardiovascular O 0
and O 0
renal O 0
vascular O 0
effects O 0
of O 0
fenoldopam B-Chemical 0
and O 0
sodium B-Chemical 0
nitroprusside B-Chemical 0
in O 0
ten O 0
dogs O 0
under O 0
halothane B-Chemical 0
general O 0
anaesthesia O 0
. O 0

Mean O 0
arterial O 0
pressure O 0
was O 0
decreased O 0
30 O 0
+ O 0
/ O 0
- O 0
8 O 0
per O 0
cent O 0
from O 0
control O 0
with O 0
infusion O 0
of O 0
fenoldopam B-Chemical 0
( O 0
3 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
0 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
) O 0
and O 0
34 O 0
+ O 0
/ O 0
- O 0
4 O 0
per O 0
cent O 0
with O 0
infusion O 0
of O 0
sodium B-Chemical 0
nitroprusside B-Chemical 0
( O 0
5 O 0
. O 0
9 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
) O 0
( O 0
NS O 0
) O 0
. O 0

Renal O 0
blood O 0
flow O 0
( O 0
RBF O 0
) O 0
increased O 0
during O 0
fenoldopam B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
11 O 0
+ O 0
/ O 0
- O 0
7 O 0
per O 0
cent O 0
and O 0
decreased O 0
21 O 0
+ O 0
/ O 0
- O 0
8 O 0
per O 0
cent O 0
during O 0
sodium B-Chemical 0
nitroprusside B-Chemical 0
- O 0
induced O 0
hypotension 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

Sodium O 0
nitroprusside B-Chemical 0
is O 0
a O 0
non O 0
- O 0
selective O 0
arteriolar O 0
and O 0
venous O 0
vasodilator O 0
that O 0
can O 0
produce O 0
redistribution O 0
of O 0
blood O 0
flow O 0
away O 0
from O 0
the O 0
kidney O 0
during O 0
induced O 0
hypotension B-Disease 0
. O 0

Fenoldopam O 0
is O 0
a O 0
selective O 0
dopamine B-Chemical 0
- O 0
1 O 0
( O 0
DA1 O 0
) O 0
receptor O 0
agonist O 0
that O 0
causes O 0
vasodilatation O 0
to O 0
the O 0
kidney O 0
and O 0
other O 0
organs O 0
with O 0
DA1 O 0
receptors O 0
and O 0
preserves O 0
blood O 0
flow O 0
to O 0
the O 0
kidney O 0
during O 0
induced O 0
hypotension B-Disease 0
. O 0

Seizures B-Disease 0
associated O 0
with O 0
levofloxacin B-Chemical 0
: O 0
case O 0
presentation O 0
and O 0
literature O 0
review O 0
. O 0

PURPOSE O 0
: O 0
We O 0
present O 0
a O 0
case O 0
of O 0
a O 0
patient O 0
who O 0
developed O 0
seizures B-Disease 0
shortly O 0
after O 0
initiating O 0
treatment O 0
with O 0
levofloxacin B-Chemical 0
and O 0
to O 0
discuss O 0
the O 0
potential O 0
drug O 0
- O 0
drug O 0
interactions O 0
related O 0
to O 0
the O 0
inhibition O 0
of O 0
cytochrome O 0
P450 O 0
( O 0
CYP O 0
) O 0
1A2 O 0
in O 0
this O 0
case O 0
, O 0
as O 0
well O 0
as O 0
in O 0
other O 0
cases O 0
, O 0
of O 0
levofloxacin B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
. O 0

METHODS O 0
: O 0
Several O 0
biomedical O 0
databases O 0
were O 0
searched O 0
including O 0
MEDLINE O 0
, O 0
Cochrane O 0
and O 0
Ovid O 0
. O 0

The O 0
main O 0
search O 0
terms O 0
utilized O 0
were O 0
case O 0
report O 0
and O 0
levofloxacin B-Chemical 0
. O 0

The O 0
search O 0
was O 0
limited O 0
to O 0
studies O 0
published O 0
in O 0
English O 0
. O 0

RESULTS O 0
: O 0
Six O 0
cases O 0
of O 0
levofloxacin B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
have O 0
been O 0
reported O 0
in O 0
the O 0
literature O 0
. O 0

Drug O 0
- O 0
drug O 0
interactions O 0
related O 0
to O 0
the O 0
inhibition O 0
of O 0
CYP1A2 O 0
by O 0
levofloxacin B-Chemical 0
are O 0
likely O 0
involved O 0
in O 0
the O 0
clinical O 0
outcome O 0
of O 0
these O 0
cases O 0
. O 0

CONCLUSIONS O 0
: O 0
Clinicians O 0
are O 0
exhorted O 0
to O 0
pay O 0
close O 0
attention O 0
when O 0
initiating O 0
levofloxacin B-Chemical 0
therapy O 0
in O 0
patients O 0
taking O 0
medications O 0
with O 0
epileptogenic O 0
properties O 0
that O 0
are O 0
CYP1A2 O 0
substrates O 0
. O 0

Dextran B-Chemical 0
- O 0
etodolac B-Chemical 0
conjugates O 0
: O 0
synthesis O 0
, O 0
in O 0
vitro O 0
and O 0
in O 0
vivo O 0
evaluation O 0
. O 0

Etodolac B-Chemical 0
( O 0
E B-Chemical 0
) O 0
, O 0
is O 0
a O 0
non O 0
- O 0
narcotic O 0
analgesic O 0
and O 0
antiinflammatory O 0
drug O 0
. O 0

A O 0
biodegradable O 0
polymer O 0
dextran B-Chemical 0
has O 0
been O 0
utilized O 0
as O 0
a O 0
carrier O 0
for O 0
synthesis O 0
of O 0
etodolac B-Chemical 0
- O 0
dextran B-Chemical 0
conjugates O 0
( O 0
ED O 0
) O 0
to O 0
improve O 0
its O 0
aqueous O 0
solubility O 0
and O 0
reduce O 0
gastrointestinal O 0
side O 0
effects O 0
. O 0

An O 0
activated O 0
moiety O 0
, O 0
i O 0
. O 0
e O 0
. O 0
N B-Chemical 0
- I-Chemical 0
acylimidazole I-Chemical 0
derivative O 0
of O 0
etodolac B-Chemical 0
( O 0
EAI B-Chemical 0
) O 0
, O 0
was O 0
condensed O 0
with O 0
the O 0
polysaccharide O 0
polymer O 0
dextran B-Chemical 0
of O 0
different O 0
molecular O 0
weights O 0
( O 0
40000 O 0
, O 0
60000 O 0
, O 0
110000 O 0
and O 0
200000 O 0
) O 0
. O 0

IR O 0
spectral O 0
data O 0
confirmed O 0
formation O 0
of O 0
ester O 0
bonding O 0
in O 0
the O 0
conjugates O 0
. O 0

Etodolac B-Chemical 0
contents O 0
were O 0
evaluated O 0
by O 0
UV O 0
- O 0
spectrophotometric O 0
analysis O 0
. O 0

The O 0
molecular O 0
weights O 0
were O 0
determined O 0
by O 0
measuring O 0
viscosity O 0
using O 0
the O 0
Mark O 0
- O 0
Howink O 0
- O 0
Sakurada O 0
equation O 0
. O 0

In O 0
vitro O 0
hydrolysis O 0
of O 0
ED O 0
was O 0
done O 0
in O 0
aqueous O 0
buffers O 0
( O 0
pH O 0
1 O 0
. O 0
2 O 0
, O 0
7 O 0
. O 0
4 O 0
, O 0
9 O 0
) O 0
and O 0
in O 0
80 O 0
% O 0
( O 0
v O 0
/ O 0
v O 0
) O 0
human O 0
plasma O 0
( O 0
pH O 0
7 O 0
. O 0
4 O 0
) O 0
. O 0

At O 0
pH O 0
9 O 0
, O 0
a O 0
higher O 0
rate O 0
of O 0
etodolac B-Chemical 0
release O 0
from O 0
ED O 0
was O 0
observed O 0
as O 0
compared O 0
to O 0
aqueous O 0
buffer O 0
of O 0
pH O 0
7 O 0
. O 0
4 O 0
and O 0
80 O 0
% O 0
human O 0
plasma O 0
( O 0
pH O 0
7 O 0
. O 0
4 O 0
) O 0
, O 0
following O 0
first O 0
- O 0
order O 0
kinetics O 0
. O 0

In O 0
vivo O 0
investigations O 0
were O 0
performed O 0
in O 0
animals O 0
. O 0

Acute O 0
analgesic O 0
and O 0
antiinflammatory O 0
activities O 0
were O 0
ascertained O 0
using O 0
acetic B-Chemical 0
acid I-Chemical 0
induced O 0
writhing B-Disease 0
model O 0
( O 0
mice O 0
) O 0
and O 0
carrageenan B-Chemical 0
- O 0
induced O 0
rat O 0
paw O 0
edema B-Disease 0
model O 0
, O 0
respectively O 0
. O 0

In O 0
comparison O 0
to O 0
control O 0
, O 0
E B-Chemical 0
and O 0
ED1 O 0
- O 0
ED4 O 0
showed O 0
highly O 0
significant O 0
analgesic O 0
and O 0
antiinflammatory O 0
activities O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Biological O 0
evaluation O 0
suggested O 0
that O 0
conjugates O 0
( O 0
ED1 O 0
- O 0
ED4 O 0
) O 0
retained O 0
comparable O 0
analgesic O 0
and O 0
antiinflammatory O 0
activities O 0
with O 0
remarkably O 0
reduced O 0
ulcerogenicity O 0
as O 0
compared O 0
to O 0
their O 0
parent O 0
drug O 0
- O 0
- O 0
etodolac B-Chemical 0
. O 0

The O 0
antiarrhythmic O 0
effect O 0
and O 0
possible O 0
ionic O 0
mechanisms O 0
of O 0
pilocarpine B-Chemical 0
on O 0
animal O 0
models 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
effects O 0
of O 0
pilocarpine B-Chemical 0
and O 0
explore O 0
the O 0
underlying O 0
ionic O 0
mechanism O 0
, O 0
using O 0
both O 0
aconitine B-Chemical 0
- O 0
induced O 0
rat O 0
and O 0
ouabain B-Chemical 0
- O 0
induced O 0
guinea O 0
pig O 0
arrhythmia B-Disease 0
models O 0
. O 0

Confocal O 0
microscopy O 0
was O 0
used O 0
to O 0
measure O 0
intracellular O 0
free O 0
- O 0
calcium B-Chemical 0
concentrations O 0
( O 0
[ O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
] O 0
( O 0
i O 0
) O 0
) O 0
in O 0
isolated O 0
myocytes O 0
. O 0

The O 0
current O 0
data O 0
showed O 0
that O 0
pilocarpine B-Chemical 0
significantly O 0
delayed O 0
onset O 0
of O 0
arrhythmias B-Disease 0
, O 0
decreased O 0
the O 0
time O 0
course O 0
of O 0
ventricular B-Disease 0
tachycardia I-Disease 0
and I-Disease 0
fibrillation I-Disease 0
, O 0
reduced O 0
arrhythmia B-Disease 0
score O 0
, O 0
and O 0
increased O 0
the O 0
survival O 0
time O 0
of O 0
arrhythmic B-Disease 0
rats O 0
and O 0
guinea O 0
pigs O 0
. O 0

[ O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
] O 0
( O 0
i O 0
) O 0
overload O 0
induced O 0
by O 0
aconitine B-Chemical 0
or O 0
ouabain B-Chemical 0
was O 0
reduced O 0
in O 0
isolated O 0
myocytes O 0
pretreated O 0
with O 0
pilocarpine B-Chemical 0
. O 0

Moreover O 0
, O 0
M O 0
( O 0
3 O 0
) O 0
- O 0
muscarinic O 0
acetylcholine B-Chemical 0
receptor O 0
( O 0
mAChR O 0
) O 0
antagonist O 0
4 B-Chemical 0
- I-Chemical 0
DAMP I-Chemical 0
( O 0
4 B-Chemical 0
- I-Chemical 0
diphenylacetoxy I-Chemical 0
- I-Chemical 0
N I-Chemical 0
- I-Chemical 0
methylpiperidine I-Chemical 0
- I-Chemical 0
methiodide I-Chemical 0
) O 0
partially O 0
abolished O 0
the O 0
beneficial O 0
effects O 0
of O 0
pilocarpine B-Chemical 0
. O 0

These O 0
data O 0
suggest O 0
that O 0
pilocarpine B-Chemical 0
produced O 0
antiarrhythmic O 0
actions O 0
on O 0
arrhythmic B-Disease 0
rat O 0
and O 0
guinea O 0
pig O 0
models O 0
induced O 0
by O 0
aconitine B-Chemical 0
or O 0
ouabain B-Chemical 0
via O 0
stimulating O 0
the O 0
cardiac O 0
M O 0
( O 0
3 O 0
) O 0
- O 0
mAChR O 0
. O 0

The O 0
mechanism O 0
may O 0
be O 0
related O 0
to O 0
the O 0
improvement O 0
of O 0
Ca B-Chemical 0
( O 0
2 O 0
+ O 0
) O 0
handling O 0
. O 0

Effect O 0
of O 0
Hibiscus B-Chemical 0
rosa I-Chemical 0
sinensis I-Chemical 0
on O 0
reserpine B-Chemical 0
- O 0
induced O 0
neurobehavioral O 0
and O 0
biochemical O 0
alterations O 0
in O 0
rats O 0
. O 0

Effect O 0
of O 0
methanolic O 0
extract O 0
of O 0
Hibiscus B-Chemical 0
rosa I-Chemical 0
sinensis I-Chemical 0
( O 0
100 O 0
- O 0
300 O 0
mg O 0
/ O 0
kg O 0
) O 0
was O 0
studied O 0
on O 0
reserpine B-Chemical 0
- O 0
induced O 0
orofacial O 0
dyskinesia B-Disease 0
and O 0
neurochemical O 0
alterations O 0
. O 0

The O 0
rats O 0
were O 0
treated O 0
with O 0
intraperitoneal O 0
reserpine B-Chemical 0
( O 0
1 O 0
mg O 0
/ O 0
kg O 0
, O 0
ip O 0
) O 0
for O 0
3 O 0
days O 0
every O 0
other O 0
day O 0
. O 0

On O 0
day O 0
5 O 0
, O 0
vacuous O 0
chewing O 0
movements O 0
and O 0
tongue O 0
protrusions O 0
were O 0
counted O 0
for O 0
5 O 0
min O 0
. O 0

Reserpine B-Chemical 0
treated O 0
rats O 0
significantly O 0
developed O 0
vacuous O 0
chewing O 0
movements O 0
and O 0
tongue O 0
protrusions O 0
however O 0
, O 0
coadministration O 0
of O 0
Hibiscus B-Chemical 0
rosa I-Chemical 0
sinensis I-Chemical 0
roots O 0
extract O 0
( O 0
100 O 0
, O 0
200 O 0
and O 0
300 O 0
mg O 0
/ O 0
kg O 0
, O 0
per O 0
orally O 0
) O 0
attenuated O 0
the O 0
effects O 0
. O 0

Biochemical O 0
analysis O 0
of O 0
brain O 0
revealed O 0
that O 0
the O 0
reserpine B-Chemical 0
treatment O 0
significantly O 0
increased O 0
lipid O 0
peroxidation O 0
and O 0
decreased O 0
levels O 0
of O 0
superoxide B-Chemical 0
dismutase O 0
( O 0
SOD O 0
) O 0
, O 0
catalase O 0
( O 0
CAT O 0
) O 0
and O 0
glutathione B-Chemical 0
reductase O 0
( O 0
GSH O 0
) O 0
, O 0
an O 0
index O 0
of O 0
oxidative O 0
stress O 0
process O 0
. O 0

Coadministration O 0
of O 0
extract O 0
significantly O 0
reduced O 0
the O 0
lipid O 0
peroxidation O 0
and O 0
reversed O 0
the O 0
decrease O 0
in O 0
brain O 0
SOD O 0
, O 0
CAT O 0
and O 0
GSH O 0
levels O 0
. O 0

The O 0
results O 0
of O 0
the O 0
present O 0
study O 0
suggested O 0
that O 0
Hibiscus B-Chemical 0
rosa I-Chemical 0
sinensis I-Chemical 0
had O 0
a O 0
protective O 0
role O 0
against O 0
reserpine B-Chemical 0
- O 0
induced O 0
orofacial O 0
dyskinesia B-Disease 0
and O 0
oxidative O 0
stress O 0
. O 0

Dynamic O 0
response O 0
of O 0
blood O 0
vessel O 0
in O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
. O 0

In O 0
this O 0
study O 0
we O 0
postulated O 0
that O 0
during O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
induced O 0
by O 0
gentamicin B-Chemical 0
the O 0
transient O 0
or O 0
dynamic O 0
response O 0
of O 0
blood O 0
vessels O 0
could O 0
be O 0
affected O 0
, O 0
and O 0
that O 0
antioxidants O 0
can O 0
prevent O 0
the O 0
changes O 0
in O 0
dynamic O 0
responses O 0
of O 0
blood O 0
vessels O 0
. O 0

The O 0
new O 0
approach O 0
to O 0
ex O 0
vivo O 0
blood O 0
vessel O 0
experiments O 0
in O 0
which O 0
not O 0
only O 0
the O 0
end O 0
points O 0
of O 0
vessels O 0
response O 0
within O 0
the O 0
time O 0
interval O 0
is O 0
considered O 0
, O 0
but O 0
also O 0
dynamics O 0
of O 0
this O 0
response O 0
, O 0
was O 0
used O 0
in O 0
this O 0
paper O 0
. O 0

Our O 0
results O 0
confirm O 0
the O 0
alteration O 0
in O 0
dynamic O 0
response O 0
of O 0
blood O 0
vessels O 0
during O 0
the O 0
change O 0
of O 0
pressure O 0
in O 0
gentamicin B-Chemical 0
- O 0
treated O 0
animals O 0
. O 0

The O 0
beneficial O 0
effects O 0
of O 0
vitamin B-Chemical 0
C I-Chemical 0
administration O 0
to O 0
gentamicin B-Chemical 0
- O 0
treated O 0
animals O 0
are O 0
also O 0
confirmed O 0
through O 0
: O 0
lower O 0
level O 0
of O 0
blood O 0
urea B-Chemical 0
and O 0
creatinine B-Chemical 0
and O 0
higher O 0
level O 0
of O 0
potassium B-Chemical 0
. O 0

The O 0
pressure O 0
dynamic O 0
responses O 0
of O 0
isolated O 0
blood O 0
vessels O 0
show O 0
a O 0
faster O 0
pressure O 0
change O 0
in O 0
gentamicin B-Chemical 0
- O 0
treated O 0
animals O 0
( O 0
8 O 0
. O 0
07 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
7 O 0
s O 0
vs O 0
. O 0
5 O 0
. O 0
64 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
18 O 0
s O 0
) O 0
. O 0

Vitamin B-Chemical 0
C I-Chemical 0
administration O 0
induced O 0
slowdown O 0
of O 0
pressure O 0
change O 0
back O 0
to O 0
the O 0
control O 0
values O 0
. O 0

The O 0
pressure O 0
dynamic O 0
properties O 0
, O 0
quantitatively O 0
defined O 0
by O 0
comparative O 0
pressure O 0
dynamic O 0
and O 0
total O 0
pressure O 0
dynamic O 0
, O 0
confirm O 0
the O 0
alteration O 0
in O 0
dynamic O 0
response O 0
of O 0
blood O 0
vessels O 0
during O 0
the O 0
change O 0
of O 0
pressure O 0
in O 0
gentamicin B-Chemical 0
- O 0
treated O 0
animals O 0
and O 0
beneficial O 0
effects O 0
of O 0
vitamin B-Chemical 0
C I-Chemical 0
administration O 0
. O 0

Reversible O 0
myocardial B-Disease 0
hypertrophy I-Disease 0
induced O 0
by O 0
tacrolimus B-Chemical 0
in O 0
a O 0
pediatric O 0
heart O 0
transplant O 0
recipient O 0
: O 0
case O 0
report O 0
. O 0

Tacrolimus B-Chemical 0
is O 0
a O 0
potent O 0
immunosuppressant O 0
that O 0
is O 0
frequently O 0
used O 0
in O 0
organ O 0
transplantation O 0
. O 0

However O 0
, O 0
adverse O 0
effects O 0
include O 0
cardiac B-Disease 0
toxicity I-Disease 0
. O 0

Herein O 0
we O 0
describe O 0
transient O 0
myocardial B-Disease 0
hypertrophy I-Disease 0
induced O 0
by O 0
tacrolimus B-Chemical 0
after O 0
heart O 0
transplantation O 0
. O 0

The O 0
hypertrophy B-Disease 0
caused O 0
no O 0
clinical O 0
symptoms O 0
but O 0
was O 0
noted O 0
because O 0
of O 0
elevation O 0
of O 0
plasma O 0
brain O 0
natriuretic O 0
peptide O 0
concentration O 0
and O 0
confirmed O 0
at O 0
echocardiography O 0
. O 0

Initially O 0
, O 0
allograft O 0
rejection O 0
was O 0
feared O 0
; O 0
however O 0
, O 0
myocardial O 0
biopsy O 0
samples O 0
revealed O 0
only O 0
interstitial O 0
edema B-Disease 0
and O 0
mild O 0
myocardial B-Disease 0
hypertrophy I-Disease 0
; O 0
neither O 0
cellular O 0
nor O 0
humoral O 0
rejection O 0
was O 0
detected O 0
. O 0

The O 0
blood O 0
tacrolimus B-Chemical 0
concentration O 0
was O 0
higher O 0
than O 0
usual O 0
at O 0
that O 0
time O 0
; O 0
thus O 0
, O 0
tacrolimus B-Chemical 0
dosage O 0
was O 0
reduced O 0
. O 0

Myocardial B-Disease 0
hypertrophy I-Disease 0
completely O 0
resolved O 0
upon O 0
reducing O 0
the O 0
target O 0
concentration O 0
of O 0
tacrolimus B-Chemical 0
and O 0
did O 0
not O 0
recur O 0
, O 0
as O 0
confirmed O 0
at O 0
echocardiography O 0
and O 0
myocardial O 0
biopsy O 0
. O 0

Thus O 0
, O 0
we O 0
conclude O 0
that O 0
tacrolimus B-Chemical 0
induces O 0
reversible O 0
myocardial B-Disease 0
hypertrophy I-Disease 0
. O 0

In O 0
patients O 0
receiving O 0
tacrolimus B-Chemical 0
therapy O 0
, O 0
blood O 0
concentration O 0
should O 0
be O 0
carefully O 0
controlled O 0
and O 0
extreme O 0
attention O 0
paid O 0
to O 0
cardiac O 0
involvement O 0
. O 0

Nimodipine B-Chemical 0
prevents O 0
memory B-Disease 0
impairment I-Disease 0
caused O 0
by O 0
nitroglycerin B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
in O 0
adult O 0
mice O 0
. O 0

BACKGROUND O 0
: O 0
Hypotension B-Disease 0
and O 0
a O 0
resultant O 0
decrease O 0
in O 0
cerebral O 0
blood O 0
flow O 0
have O 0
been O 0
implicated O 0
in O 0
the O 0
development O 0
of O 0
cognitive B-Disease 0
dysfunction I-Disease 0
. O 0

We O 0
tested O 0
the O 0
hypothesis O 0
that O 0
nimodipine B-Chemical 0
( O 0
NIMO B-Chemical 0
) O 0
administered O 0
at O 0
the O 0
onset O 0
of O 0
nitroglycerin B-Chemical 0
( O 0
NTG B-Chemical 0
) O 0
- O 0
induced O 0
hypotension B-Disease 0
would O 0
preserve O 0
long O 0
- O 0
term O 0
associative O 0
memory O 0
. O 0

METHODS O 0
: O 0
The O 0
passive O 0
avoidance O 0
( O 0
PA O 0
) O 0
paradigm O 0
was O 0
used O 0
to O 0
assess O 0
memory O 0
retention O 0
. O 0

For O 0
PA O 0
training O 0
, O 0
latencies O 0
( O 0
seconds O 0
) O 0
were O 0
recorded O 0
for O 0
entry O 0
from O 0
a O 0
suspended O 0
platform O 0
into O 0
a O 0
Plexiglas O 0
tube O 0
where O 0
a O 0
shock O 0
was O 0
automatically O 0
delivered O 0
. O 0

Latencies O 0
were O 0
recorded O 0
48 O 0
h O 0
later O 0
for O 0
a O 0
testing O 0
trial O 0
. O 0

Ninety O 0
- O 0
six O 0
Swiss O 0
- O 0
Webster O 0
mice O 0
( O 0
30 O 0
- O 0
35 O 0
g O 0
, O 0
6 O 0
- O 0
8 O 0
wk O 0
) O 0
, O 0
were O 0
randomized O 0
into O 0
6 O 0
groups O 0
1 O 0
) O 0
saline O 0
( O 0
control O 0
) O 0
, O 0
2 O 0
) O 0
NTG B-Chemical 0
immediately O 0
after O 0
learning O 0
, O 0
3 O 0
) O 0
NTG B-Chemical 0
3 O 0
h O 0
after O 0
learning O 0
, O 0
4 O 0
) O 0
NTG B-Chemical 0
and O 0
NIMO B-Chemical 0
, O 0
5 O 0
) O 0
vehicle O 0
, O 0
and O 0
6 O 0
) O 0
NIMO B-Chemical 0
alone O 0
. O 0

The O 0
extent O 0
of O 0
hypotension B-Disease 0
and O 0
changes O 0
in O 0
brain O 0
tissue O 0
oxygenation O 0
( O 0
PbtO O 0
( O 0
2 O 0
) O 0
) O 0
and O 0
in O 0
cerebral O 0
blood O 0
flow O 0
were O 0
studied O 0
in O 0
a O 0
separate O 0
group O 0
of O 0
animals O 0
. O 0

RESULTS O 0
: O 0
All O 0
groups O 0
exhibited O 0
similar O 0
training O 0
latencies O 0
( O 0
17 O 0
. O 0
0 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
6 O 0
s O 0
) O 0
. O 0

Mice O 0
subjected O 0
to O 0
hypotensive B-Disease 0
episodes O 0
showed O 0
a O 0
significant O 0
decrease O 0
in O 0
latency O 0
time O 0
( O 0
178 O 0
+ O 0
/ O 0
- O 0
156 O 0
s O 0
) O 0
compared O 0
with O 0
those O 0
injected O 0
with O 0
saline O 0
, O 0
NTG B-Chemical 0
+ O 0
NIMO B-Chemical 0
, O 0
or O 0
delayed O 0
NTG B-Chemical 0
( O 0
580 O 0
+ O 0
/ O 0
- O 0
81 O 0
s O 0
, O 0
557 O 0
+ O 0
/ O 0
- O 0
67 O 0
s O 0
, O 0
and O 0
493 O 0
+ O 0
/ O 0
- O 0
146 O 0
s O 0
, O 0
respectively O 0
) O 0
. O 0

A O 0
Kruskal O 0
- O 0
Wallis O 0
1 O 0
- O 0
way O 0
analysis O 0
of O 0
variance O 0
indicated O 0
a O 0
significant O 0
difference O 0
among O 0
the O 0
4 O 0
treatment O 0
groups O 0
( O 0
H O 0
= O 0
15 O 0
. O 0
34 O 0
; O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

In O 0
a O 0
separate O 0
group O 0
of O 0
mice O 0
not O 0
subjected O 0
to O 0
behavioral O 0
studies O 0
, O 0
the O 0
same O 0
dose O 0
of O 0
NTG B-Chemical 0
( O 0
n O 0
= O 0
3 O 0
) O 0
and O 0
NTG B-Chemical 0
+ O 0
NIMO B-Chemical 0
( O 0
n O 0
= O 0
3 O 0
) O 0
caused O 0
mean O 0
arterial O 0
blood O 0
pressure O 0
to O 0
decrease O 0
from O 0
85 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
8 O 0
mm O 0
Hg O 0
sem O 0
to O 0
31 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
8 O 0
mm O 0
Hg O 0
sem O 0
and O 0
from O 0
86 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
7 O 0
mm O 0
Hg O 0
sem O 0
to O 0
32 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
mm O 0
Hg O 0
sem O 0
, O 0
respectively O 0
. O 0

Mean O 0
arterial O 0
blood O 0
pressure O 0
in O 0
mice O 0
treated O 0
with O 0
NIMO B-Chemical 0
alone O 0
decreased O 0
from O 0
88 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
8 O 0
mm O 0
Hg O 0
to O 0
80 O 0
. O 0
0 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
9 O 0
mm O 0
Hg O 0
. O 0

The O 0
intergroup O 0
difference O 0
was O 0
statistically O 0
significant O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

PbtO O 0
( O 0
2 O 0
) O 0
decreased O 0
from O 0
51 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
5 O 0
mm O 0
Hg O 0
sem O 0
to O 0
33 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
5 O 0
. O 0
2 O 0
mm O 0
Hg O 0
sem O 0
in O 0
the O 0
NTG B-Chemical 0
group O 0
and O 0
from O 0
38 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
6 O 0
. O 0
1 O 0
mm O 0
Hg O 0
sem O 0
to O 0
25 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
0 O 0
mm O 0
Hg O 0
sem O 0
in O 0
the O 0
NTG B-Chemical 0
+ O 0
NIMO B-Chemical 0
groups O 0
, O 0
respectively O 0
. O 0

There O 0
were O 0
no O 0
significant O 0
differences O 0
among O 0
groups O 0
. O 0

CONCLUSION O 0
: O 0
In O 0
a O 0
PA O 0
retention O 0
paradigm O 0
, O 0
the O 0
injection O 0
of O 0
NTG B-Chemical 0
immediately O 0
after O 0
learning O 0
produced O 0
a O 0
significant O 0
impairment O 0
of O 0
long O 0
- O 0
term O 0
associative O 0
memory O 0
in O 0
mice O 0
, O 0
whereas O 0
delayed O 0
induced O 0
hypotension B-Disease 0
had O 0
no O 0
effect O 0
. O 0

NIMO B-Chemical 0
attenuated O 0
the O 0
disruption O 0
in O 0
consolidation O 0
of O 0
long O 0
- O 0
term O 0
memory O 0
caused O 0
by O 0
NTG B-Chemical 0
but O 0
did O 0
not O 0
improve O 0
latency O 0
in O 0
the O 0
absence O 0
of O 0
hypotension B-Disease 0
. O 0

The O 0
observed O 0
effect O 0
of O 0
NIMO B-Chemical 0
may O 0
have O 0
been O 0
attributable O 0
to O 0
the O 0
preservation O 0
of O 0
calcium B-Chemical 0
homeostasis O 0
during O 0
hypotension B-Disease 0
, O 0
because O 0
there O 0
were O 0
no O 0
differences O 0
in O 0
the O 0
PbtO O 0
( O 0
2 O 0
) O 0
indices O 0
among O 0
groups O 0
. O 0

Metabotropic O 0
glutamate B-Chemical 0
7 O 0
receptor O 0
subtype O 0
modulates O 0
motor O 0
symptoms O 0
in O 0
rodent O 0
models O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

Metabotropic O 0
glutamate B-Chemical 0
( O 0
mGlu O 0
) O 0
receptors O 0
modulate O 0
synaptic O 0
transmission O 0
in O 0
the O 0
central O 0
nervous O 0
system O 0
and O 0
represent O 0
promising O 0
therapeutic O 0
targets O 0
for O 0
symptomatic O 0
treatment O 0
of 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

Among O 0
the O 0
eight O 0
mGlu O 0
receptor O 0
subtypes O 0
, O 0
mGlu7 O 0
receptor O 0
is O 0
prominently O 0
expressed O 0
in O 0
the O 0
basal O 0
ganglia O 0
, O 0
but O 0
its O 0
role O 0
in O 0
restoring O 0
motor O 0
function O 0
in O 0
animal O 0
models O 0
of O 0
PD B-Disease 0
is O 0
not O 0
known O 0
. O 0

The O 0
effects O 0
of O 0
N B-Chemical 0
, I-Chemical 0
N I-Chemical 0
' I-Chemical 0
- I-Chemical 0
dibenzhydrylethane I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
, I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
diamine I-Chemical 0
dihydrochloride I-Chemical 0
( O 0
AMN082 B-Chemical 0
) O 0
, O 0
the O 0
first O 0
selective O 0
allosteric O 0
activator O 0
of O 0
mGlu7 O 0
receptors O 0
, O 0
were O 0
thus O 0
tested O 0
in O 0
different O 0
rodent O 0
models O 0
of O 0
PD B-Disease 0
. O 0

Here O 0
, O 0
we O 0
show O 0
that O 0
oral O 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
or O 0
intrastriatal O 0
administration O 0
( O 0
0 O 0
. O 0
1 O 0
and O 0
0 O 0
. O 0
5 O 0
nmol O 0
) O 0
of O 0
AMN082 B-Chemical 0
reverses O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
in O 0
rats O 0
. O 0

AMN082 B-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
and O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
reduces O 0
apomorphine B-Chemical 0
- O 0
induced O 0
rotations O 0
in O 0
unilateral O 0
6 B-Chemical 0
- I-Chemical 0
hydroxydopamine I-Chemical 0
( O 0
6 B-Chemical 0
- I-Chemical 0
OHDA I-Chemical 0
) O 0
- O 0
lesioned O 0
rats O 0
. O 0

In O 0
a O 0
more O 0
complex O 0
task O 0
commonly O 0
used O 0
to O 0
evaluate O 0
major O 0
akinetic B-Disease 0
symptoms O 0
of O 0
PD B-Disease 0
patients O 0
, O 0
5 O 0
mg O 0
/ O 0
kg O 0
AMN082 B-Chemical 0
reverses O 0
the O 0
increased O 0
reaction O 0
time O 0
to O 0
respond O 0
to O 0
a O 0
cue O 0
of O 0
bilateral O 0
6 B-Chemical 0
- I-Chemical 0
OHDA I-Chemical 0
- O 0
lesioned O 0
rats O 0
. O 0

In O 0
addition O 0
, O 0
AMN082 B-Chemical 0
reduces O 0
the O 0
duration O 0
of O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
in O 0
a O 0
mGlu7 O 0
receptor O 0
- O 0
dependent O 0
manner O 0
in O 0
wild O 0
- O 0
type O 0
but O 0
not O 0
mGlu7 O 0
receptor O 0
knockout O 0
mice O 0
. O 0

Higher O 0
doses O 0
of O 0
AMN082 B-Chemical 0
( O 0
10 O 0
and O 0
20 O 0
mg O 0
/ O 0
kg O 0
p O 0
. O 0
o O 0
. O 0
) O 0
have O 0
no O 0
effect O 0
on O 0
the O 0
same O 0
models O 0
of O 0
PD B-Disease 0
. O 0

Overall O 0
these O 0
findings O 0
suggest O 0
that O 0
mGlu7 O 0
receptor O 0
activation O 0
can O 0
reverse O 0
motor O 0
dysfunction O 0
associated O 0
with O 0
reduced O 0
dopamine B-Chemical 0
activity O 0
. O 0

Selective O 0
ligands O 0
of O 0
mGlu7 O 0
receptor O 0
subtypes O 0
may O 0
thus O 0
be O 0
considered O 0
as O 0
promising O 0
compounds O 0
for O 0
the O 0
development O 0
of O 0
antiparkinsonian O 0
therapeutic O 0
strategies O 0
. O 0

Sorafenib B-Chemical 0
- O 0
induced O 0
acute O 0
myocardial B-Disease 0
infarction I-Disease 0
due O 0
to O 0
coronary B-Disease 0
artery I-Disease 0
spasm I-Disease 0
. O 0

A O 0
65 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
advanced O 0
renal B-Disease 0
cell I-Disease 0
carcinoma I-Disease 0
was O 0
admitted O 0
due O 0
to O 0
continuing O 0
chest B-Disease 0
pain I-Disease 0
at O 0
rest O 0
. O 0

Two O 0
weeks O 0
before O 0
his O 0
admission O 0
, O 0
sorafenib B-Chemical 0
had O 0
been O 0
started O 0
. O 0

He O 0
was O 0
diagnosed O 0
with O 0
non O 0
- O 0
ST O 0
- O 0
elevation O 0
myocardial B-Disease 0
infarction I-Disease 0
by O 0
laboratory O 0
data O 0
and O 0
electrocardiogram O 0
. O 0

Enhanced O 0
heart O 0
magnetic O 0
resonance O 0
imaging O 0
also O 0
showed O 0
subendocardial B-Disease 0
infarction I-Disease 0
. O 0

However O 0
, O 0
there O 0
was O 0
no O 0
stenosis O 0
in O 0
coronary O 0
arteries O 0
on O 0
angiography O 0
. O 0

Coronary B-Disease 0
artery I-Disease 0
spasm I-Disease 0
was O 0
induced O 0
by O 0
a O 0
provocative O 0
test O 0
. O 0

Cessation O 0
of O 0
sorafenib B-Chemical 0
and O 0
administration O 0
of O 0
Ca B-Chemical 0
- O 0
channel O 0
blocker O 0
and O 0
nitrates B-Chemical 0
ameliorated O 0
his O 0
symptoms O 0
, O 0
but O 0
relapse O 0
occurred O 0
after O 0
resumption O 0
of O 0
sorafenib B-Chemical 0
. O 0

Addition O 0
of O 0
oral O 0
nicorandil B-Chemical 0
reduced O 0
his O 0
symptoms O 0
and O 0
maintained O 0
stable B-Disease 0
angina I-Disease 0
status O 0
. O 0

We O 0
report O 0
the O 0
first O 0
case O 0
of O 0
sorafenib B-Chemical 0
- O 0
induced O 0
coronary B-Disease 0
artery I-Disease 0
spasm I-Disease 0
. O 0

Sorafenib B-Chemical 0
is O 0
a O 0
multikinase O 0
inhibitor O 0
that O 0
targets O 0
signaling O 0
pathways O 0
necessary O 0
for O 0
cellular O 0
proliferation O 0
and O 0
survival O 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
the O 0
Rho O 0
/ O 0
ROCK O 0
pathway O 0
has O 0
an O 0
important O 0
role O 0
in O 0
the O 0
pathogenesis O 0
of O 0
coronary B-Disease 0
artery I-Disease 0
spasm I-Disease 0
. O 0

Our O 0
report O 0
may O 0
show O 0
an O 0
adverse O 0
effect O 0
on O 0
the O 0
Rho O 0
/ O 0
ROCK O 0
pathway O 0
by O 0
sorafenib B-Chemical 0
use O 0
. O 0

A O 0
novel O 0
animal O 0
model O 0
to O 0
evaluate O 0
the O 0
ability O 0
of O 0
a O 0
drug O 0
delivery O 0
system O 0
to O 0
promote O 0
the O 0
passage O 0
through O 0
the O 0
BBB 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
explore O 0
the O 0
potentiality O 0
of O 0
a O 0
novel O 0
animal O 0
model O 0
to O 0
be O 0
used O 0
for O 0
the O 0
in O 0
vivo O 0
evaluation O 0
of O 0
the O 0
ability O 0
of O 0
a O 0
drug O 0
delivery O 0
system O 0
to O 0
promote O 0
the O 0
passage O 0
through O 0
the O 0
blood O 0
- O 0
brain O 0
barrier O 0
( O 0
BBB O 0
) O 0
and O 0
/ O 0
or O 0
to O 0
improve O 0
the O 0
brain O 0
localization O 0
of O 0
a O 0
bioactive O 0
compound O 0
. O 0

A O 0
Tween O 0
80 O 0
- O 0
coated O 0
poly B-Chemical 0
- I-Chemical 0
L I-Chemical 0
- I-Chemical 0
lactid I-Chemical 0
acid I-Chemical 0
nanoparticles O 0
was O 0
used O 0
as O 0
a O 0
model O 0
of O 0
colloidal O 0
drug O 0
delivery O 0
system O 0
, O 0
able O 0
to O 0
trespass O 0
the O 0
BBB O 0
. O 0

Tacrine B-Chemical 0
, O 0
administered O 0
in O 0
LiCl B-Chemical 0
pre O 0
- O 0
treated O 0
rats O 0
, O 0
induces O 0
electrocorticographic O 0
seizures B-Disease 0
and O 0
delayed O 0
hippocampal B-Disease 0
damage I-Disease 0
. O 0

The O 0
toxic O 0
effects O 0
of O 0
tacrine B-Chemical 0
- O 0
loaded O 0
poly B-Chemical 0
- I-Chemical 0
L I-Chemical 0
- I-Chemical 0
lactid I-Chemical 0
acid I-Chemical 0
nanoparticles O 0
( O 0
5mg O 0
/ O 0
kg O 0
) O 0
, O 0
a O 0
saline O 0
solution O 0
of O 0
tacrine B-Chemical 0
( O 0
5mg O 0
/ O 0
kg O 0
) O 0
and O 0
an O 0
empty O 0
colloidal O 0
nanoparticle O 0
suspension O 0
were O 0
compared O 0
following O 0
i O 0
. O 0
p O 0
. O 0
administration O 0
in O 0
LiCl B-Chemical 0
- O 0
pre O 0
- O 0
treated O 0
Wistar O 0
rats O 0
. O 0

All O 0
the O 0
animals O 0
treated O 0
with O 0
tacrine B-Chemical 0
- O 0
loaded O 0
nanoparticles O 0
showed O 0
an O 0
earlier O 0
outcome O 0
of O 0
CNS O 0
adverse O 0
symptoms O 0
, O 0
i O 0
. O 0
e O 0
. O 0
epileptic B-Disease 0
onset O 0
, O 0
with O 0
respect O 0
to O 0
those O 0
animals O 0
treated O 0
with O 0
the O 0
free O 0
compound O 0
( O 0
10 O 0
min O 0
vs O 0
. O 0
22 O 0
min O 0
respectively O 0
) O 0
. O 0

In O 0
addition O 0
, O 0
tacrine B-Chemical 0
- O 0
loaded O 0
nanoparticles O 0
administration O 0
induced O 0
damage B-Disease 0
of I-Disease 0
neuronal I-Disease 0
cells I-Disease 0
in O 0
CA1 O 0
field O 0
of O 0
the O 0
hippocampus O 0
in O 0
all O 0
treated O 0
animals O 0
, O 0
while O 0
the O 0
saline O 0
solution O 0
of O 0
tacrine B-Chemical 0
only O 0
in O 0
60 O 0
% O 0
of O 0
animals O 0
. O 0

Empty O 0
nanoparticles O 0
provided O 0
similar O 0
results O 0
to O 0
control O 0
( O 0
saline O 0
- O 0
treated O 0
) O 0
group O 0
of O 0
animals O 0
. O 0

In O 0
conclusion O 0
, O 0
the O 0
evaluation O 0
of O 0
time O 0
- O 0
to O 0
- O 0
onset O 0
of O 0
symptoms O 0
and O 0
the O 0
severity O 0
of O 0
neurodegenerative O 0
processes O 0
induced O 0
by O 0
the O 0
tacrine B-Chemical 0
- O 0
lithium B-Chemical 0
model O 0
of O 0
epilepsy B-Disease 0
in O 0
the O 0
rat O 0
, O 0
could O 0
be O 0
used O 0
to O 0
evaluate O 0
preliminarily O 0
the O 0
capability O 0
of O 0
a O 0
drug O 0
delivery O 0
system O 0
to O 0
trespass O 0
( O 0
or O 0
not O 0
) O 0
the O 0
BBB O 0
in O 0
vivo O 0
. O 0

High O 0
- O 0
dose O 0
tranexamic B-Chemical 0
Acid I-Chemical 0
is O 0
associated O 0
with O 0
nonischemic O 0
clinical O 0
seizures B-Disease 0
in O 0
cardiac O 0
surgical O 0
patients O 0
. O 0

BACKGROUND O 0
: O 0
In O 0
2 O 0
separate O 0
centers O 0
, O 0
we O 0
observed O 0
a O 0
notable O 0
increase O 0
in O 0
the O 0
incidence O 0
of O 0
postoperative O 0
convulsive B-Disease 0
seizures B-Disease 0
from O 0
1 O 0
. O 0
3 O 0
% O 0
to O 0
3 O 0
. O 0
8 O 0
% O 0
in O 0
patients O 0
having O 0
undergone O 0
major O 0
cardiac O 0
surgical O 0
procedures O 0
. O 0

These O 0
events O 0
were O 0
temporally O 0
coincident O 0
with O 0
the O 0
initial O 0
use O 0
of O 0
high O 0
- O 0
dose O 0
tranexamic B-Chemical 0
acid I-Chemical 0
( O 0
TXA B-Chemical 0
) O 0
therapy O 0
after O 0
withdrawal O 0
of O 0
aprotinin O 0
from O 0
general O 0
clinical O 0
usage O 0
. O 0

The O 0
purpose O 0
of O 0
this O 0
review O 0
was O 0
to O 0
perform O 0
a O 0
retrospective O 0
analysis O 0
to O 0
examine O 0
whether O 0
there O 0
was O 0
a O 0
relation O 0
between O 0
TXA B-Chemical 0
usage O 0
and O 0
seizures B-Disease 0
after O 0
cardiac O 0
surgery O 0
. O 0

METHODS O 0
: O 0
An O 0
in O 0
- O 0
depth O 0
chart O 0
review O 0
was O 0
undertaken O 0
in O 0
all O 0
24 O 0
patients O 0
who O 0
developed O 0
perioperative O 0
seizures B-Disease 0
. O 0

Electroencephalographic O 0
activity O 0
was O 0
recorded O 0
in O 0
11 O 0
of O 0
these O 0
patients O 0
, O 0
and O 0
all O 0
patients O 0
had O 0
a O 0
formal O 0
neurological O 0
evaluation O 0
and O 0
brain O 0
imaging O 0
studies O 0
. O 0

RESULTS O 0
: O 0
Twenty O 0
- O 0
one O 0
of O 0
the O 0
24 O 0
patients O 0
did O 0
not O 0
have O 0
evidence O 0
of O 0
new O 0
cerebral B-Disease 0
ischemic I-Disease 0
injury I-Disease 0
, O 0
but O 0
seizures B-Disease 0
were O 0
likely O 0
due O 0
to O 0
ischemic B-Disease 0
brain I-Disease 0
injury I-Disease 0
in O 0
3 O 0
patients O 0
. O 0

All O 0
patients O 0
with O 0
seizures B-Disease 0
did O 0
not O 0
have O 0
permanent O 0
neurological B-Disease 0
abnormalities I-Disease 0
. O 0

All O 0
24 O 0
patients O 0
with O 0
seizures B-Disease 0
received O 0
high O 0
doses O 0
of O 0
TXA B-Chemical 0
intraoperatively O 0
ranging O 0
from O 0
61 O 0
to O 0
259 O 0
mg O 0
/ O 0
kg O 0
, O 0
had O 0
a O 0
mean O 0
age O 0
of O 0
69 O 0
. O 0
9 O 0
years O 0
, O 0
and O 0
21 O 0
of O 0
24 O 0
had O 0
undergone O 0
open O 0
chamber O 0
rather O 0
than O 0
coronary O 0
bypass O 0
procedures O 0
. O 0

All O 0
but O 0
one O 0
patient O 0
were O 0
managed O 0
using O 0
cardiopulmonary O 0
bypass O 0
. O 0

No O 0
evidence O 0
of O 0
brain B-Disease 0
ischemic I-Disease 0
, O 0
metabolic O 0
, O 0
or O 0
hyperthermia B-Disease 0
- O 0
induced O 0
causes O 0
for O 0
their O 0
seizures B-Disease 0
was O 0
apparent O 0
. O 0

CONCLUSION O 0
: O 0
Our O 0
results O 0
suggest O 0
that O 0
use O 0
of O 0
high O 0
- O 0
dose O 0
TXA B-Chemical 0
in O 0
older O 0
patients O 0
in O 0
conjunction O 0
with O 0
cardiopulmonary O 0
bypass O 0
and O 0
open O 0
- O 0
chamber O 0
cardiac O 0
surgery O 0
is O 0
associated O 0
with O 0
clinical O 0
seizures B-Disease 0
in O 0
susceptible O 0
patients O 0
. O 0

Electrocardiographic O 0
changes O 0
and O 0
cardiac B-Disease 0
arrhythmias I-Disease 0
in O 0
patients O 0
receiving O 0
psychotropic O 0
drugs O 0
. O 0

Eight O 0
patients O 0
had O 0
cardiac O 0
manifestations O 0
that O 0
were O 0
life O 0
- O 0
threatening O 0
in O 0
five O 0
while O 0
taking O 0
psychotropic O 0
drugs O 0
, O 0
either O 0
phenothiazines B-Chemical 0
or O 0
tricyclic O 0
antidepressants O 0
. O 0

Although O 0
most O 0
patients O 0
were O 0
receiving O 0
several O 0
drugs O 0
, O 0
Mellaril B-Chemical 0
( O 0
thioridazine B-Chemical 0
) O 0
appeared O 0
to O 0
be O 0
responsible O 0
for O 0
five O 0
cases O 0
of O 0
ventricular B-Disease 0
tachycardia I-Disease 0
, O 0
one O 0
of O 0
which O 0
was O 0
fatal O 0
in O 0
a O 0
35 O 0
year O 0
old O 0
woman O 0
. O 0

Supraventricular B-Disease 0
tachycardia I-Disease 0
developed O 0
in O 0
one O 0
patient O 0
receiving O 0
Thorazine B-Chemical 0
( O 0
chlorpromazine B-Chemical 0
) O 0
. O 0

Aventyl B-Chemical 0
( O 0
nortriptyline B-Chemical 0
) O 0
and O 0
Elavil B-Chemical 0
( O 0
amitriptyline B-Chemical 0
) O 0
each O 0
produced O 0
left B-Disease 0
bundle I-Disease 0
branch I-Disease 0
block I-Disease 0
in O 0
a O 0
73 O 0
year O 0
old O 0
woman O 0
. O 0

Electrocardiographic O 0
T O 0
and O 0
U O 0
wave O 0
abnormalities O 0
were O 0
present O 0
in O 0
most O 0
patients O 0
. O 0

The O 0
ventricular B-Disease 0
arrhythmias I-Disease 0
responded O 0
to O 0
intravenous O 0
administration O 0
of O 0
lidocaine B-Chemical 0
and O 0
to O 0
direct O 0
current O 0
electric O 0
shock O 0
; O 0
ventricular O 0
pacing O 0
was O 0
required O 0
in O 0
some O 0
instances O 0
and O 0
intravenous O 0
administration O 0
of O 0
propranolol B-Chemical 0
combined O 0
with O 0
ventricular O 0
pacing O 0
in O 0
one O 0
. O 0

The O 0
tachyarrhythmias B-Disease 0
generally O 0
subsided O 0
within O 0
48 O 0
hours O 0
after O 0
administration O 0
of O 0
the O 0
drugs O 0
was O 0
stopped O 0
. O 0

Five O 0
of O 0
the O 0
eight O 0
patients O 0
were O 0
50 O 0
years O 0
of O 0
age O 0
or O 0
younger O 0
; O 0
only O 0
one O 0
clearly O 0
had O 0
antecedent O 0
heart B-Disease 0
disease I-Disease 0
. O 0

Major O 0
cardiac B-Disease 0
arrhythmias I-Disease 0
are O 0
a O 0
potential O 0
hazard O 0
in O 0
patients O 0
without O 0
heart B-Disease 0
disease I-Disease 0
who O 0
are O 0
receiving O 0
customary O 0
therapeutic O 0
doses O 0
of O 0
psychotropic O 0
drugs O 0
. O 0

A O 0
prospective O 0
clinical O 0
trial O 0
is O 0
suggested O 0
to O 0
quantify O 0
the O 0
risk O 0
of O 0
cardiac B-Disease 0
complications I-Disease 0
to O 0
patients O 0
receiving O 0
phenothiazines B-Chemical 0
or O 0
tricyclic O 0
antidepressant O 0
drugs O 0
. O 0

Sensitivity O 0
of O 0
erythroid O 0
progenitor O 0
colonies O 0
to O 0
erythropoietin O 0
in O 0
azidothymidine B-Chemical 0
treated O 0
immunodeficient B-Disease 0
mice O 0
. O 0

The O 0
anaemia B-Disease 0
induced O 0
by O 0
3 B-Chemical 0
' I-Chemical 0
- I-Chemical 0
azido I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
' I-Chemical 0
dideoxythymidine I-Chemical 0
( O 0
AZT B-Chemical 0
) O 0
is O 0
poorly O 0
understood O 0
. O 0

We O 0
have O 0
used O 0
a O 0
murine O 0
model O 0
of O 0
AIDS B-Disease 0
, O 0
infection B-Disease 0
of O 0
female O 0
C57BL O 0
/ O 0
6 O 0
mice O 0
with O 0
LP O 0
- O 0
BM5 O 0
murine O 0
leukaemia B-Disease 0
( O 0
MuLV O 0
) O 0
virus O 0
, O 0
to O 0
determine O 0
if O 0
AZT B-Chemical 0
- O 0
induced O 0
anaemia B-Disease 0
is O 0
due O 0
, O 0
in O 0
part O 0
, O 0
to O 0
decreased O 0
responsiveness O 0
of O 0
erythropoietic O 0
precursors O 0
( O 0
BFU O 0
- O 0
e O 0
) O 0
to O 0
erythropoietin O 0
( O 0
EPO O 0
) O 0
. O 0

Mice O 0
in O 0
the O 0
early O 0
stage O 0
of O 0
LP O 0
- O 0
BM5 O 0
MuLV O 0
disease O 0
were O 0
given O 0
AZT B-Chemical 0
in O 0
their O 0
drinking O 0
water O 0
at O 0
1 O 0
. O 0
0 O 0
and O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
ml O 0
. O 0

AZT B-Chemical 0
produced O 0
anaemia B-Disease 0
in O 0
both O 0
groups O 0
, O 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
fashion O 0
. O 0

Despite O 0
the O 0
anaemia B-Disease 0
, O 0
the O 0
number O 0
of O 0
splenic O 0
and O 0
bone O 0
marrow O 0
BFU O 0
- O 0
e O 0
in O 0
AZT B-Chemical 0
treated O 0
mice O 0
increased O 0
up O 0
to O 0
five O 0
- O 0
fold O 0
over O 0
levels O 0
observed O 0
in O 0
infected O 0
untreated O 0
animals O 0
after O 0
15 O 0
d O 0
of O 0
treatment O 0
. O 0

Colony O 0
formation O 0
by O 0
splenic O 0
and O 0
bone O 0
marrow O 0
BFUe O 0
was O 0
stimulated O 0
at O 0
lower O 0
concentrations O 0
of O 0
EPO O 0
in O 0
mice O 0
receiving O 0
AZT B-Chemical 0
for O 0
15 O 0
d O 0
than O 0
for O 0
infected O 0
, O 0
untreated O 0
mice O 0
. O 0

By O 0
day O 0
30 O 0
, O 0
sensitivity O 0
of O 0
both O 0
splenic O 0
and O 0
bone O 0
marrow O 0
BFU O 0
- O 0
e O 0
of O 0
treated O 0
animals O 0
returned O 0
to O 0
that O 0
observed O 0
from O 0
cells O 0
of O 0
infected O 0
untreated O 0
animals O 0
. O 0

The O 0
mean O 0
plasma O 0
levels O 0
of O 0
EPO O 0
observed O 0
in O 0
AZT B-Chemical 0
treated O 0
mice O 0
were O 0
appropriate O 0
for O 0
the O 0
degree O 0
of O 0
anaemia B-Disease 0
observed O 0
when O 0
compared O 0
with O 0
phenylhydrazine B-Chemical 0
( O 0
PHZ B-Chemical 0
) O 0
treated O 0
mice O 0
. O 0

The O 0
numbers O 0
of O 0
BFU O 0
- O 0
e O 0
and O 0
the O 0
percentage O 0
of O 0
bone O 0
marrow O 0
erythroblasts O 0
observed O 0
were O 0
comparable O 0
in O 0
AZT B-Chemical 0
and O 0
PHZ B-Chemical 0
treated O 0
mice O 0
with O 0
similar O 0
degrees O 0
of O 0
anaemia B-Disease 0
. O 0

However O 0
, O 0
reticulocytosis B-Disease 0
was O 0
inappropriate O 0
for O 0
the O 0
degree O 0
of O 0
anaemia B-Disease 0
observed O 0
in O 0
AZT B-Chemical 0
treated O 0
infected O 0
mice O 0
. O 0

AZT B-Chemical 0
- O 0
induced O 0
peripheral O 0
anaemia B-Disease 0
in O 0
the O 0
face O 0
of O 0
increased O 0
numbers O 0
of O 0
BFU O 0
- O 0
e O 0
and O 0
increased O 0
levels O 0
of O 0
plasma O 0
EPO O 0
suggest O 0
a O 0
lesion O 0
in O 0
terminal O 0
differentiation O 0
. O 0

Sedation O 0
depth O 0
during O 0
spinal O 0
anesthesia O 0
and O 0
the O 0
development O 0
of O 0
postoperative B-Disease 0
delirium I-Disease 0
in O 0
elderly O 0
patients O 0
undergoing O 0
hip B-Disease 0
fracture I-Disease 0
repair O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
determine O 0
whether O 0
limiting O 0
intraoperative O 0
sedation O 0
depth O 0
during O 0
spinal O 0
anesthesia O 0
for O 0
hip B-Disease 0
fracture I-Disease 0
repair O 0
in O 0
elderly O 0
patients O 0
can O 0
decrease O 0
the O 0
prevalence O 0
of O 0
postoperative B-Disease 0
delirium I-Disease 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
We O 0
performed O 0
a O 0
double O 0
- O 0
blind O 0
, O 0
randomized O 0
controlled O 0
trial O 0
at O 0
an O 0
academic O 0
medical O 0
center O 0
of O 0
elderly O 0
patients O 0
( O 0
> O 0
or O 0
= O 0
65 O 0
years O 0
) O 0
without O 0
preoperative O 0
delirium B-Disease 0
or O 0
severe O 0
dementia B-Disease 0
who O 0
underwent O 0
hip B-Disease 0
fracture I-Disease 0
repair O 0
under O 0
spinal O 0
anesthesia O 0
with O 0
propofol B-Chemical 0
sedation O 0
. O 0

Sedation O 0
depth O 0
was O 0
titrated O 0
using O 0
processed O 0
electroencephalography O 0
with O 0
the O 0
bispectral O 0
index O 0
( O 0
BIS O 0
) O 0
, O 0
and O 0
patients O 0
were O 0
randomized O 0
to O 0
receive O 0
either O 0
deep O 0
( O 0
BIS O 0
, O 0
approximately O 0
50 O 0
) O 0
or O 0
light O 0
( O 0
BIS O 0
, O 0
> O 0
or O 0
= O 0
80 O 0
) O 0
sedation O 0
. O 0

Postoperative B-Disease 0
delirium I-Disease 0
was O 0
assessed O 0
as O 0
defined O 0
by 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
Third O 0
Edition O 0
Revised O 0
) O 0
criteria O 0
using O 0
the O 0
Confusion O 0
Assessment O 0
Method O 0
beginning O 0
at O 0
any O 0
time O 0
from O 0
the O 0
second O 0
day O 0
after O 0
surgery O 0
. O 0

RESULTS O 0
: O 0
From O 0
April O 0
2 O 0
, O 0
2005 O 0
, O 0
through O 0
October O 0
30 O 0
, O 0
2008 O 0
, O 0
a O 0
total O 0
of O 0
114 O 0
patients O 0
were O 0
randomized O 0
. O 0

The O 0
prevalence O 0
of O 0
postoperative B-Disease 0
delirium I-Disease 0
was O 0
significantly O 0
lower O 0
in O 0
the O 0
light O 0
sedation O 0
group O 0
( O 0
11 O 0
/ O 0
57 O 0
[ O 0
19 O 0
% O 0
] O 0
vs O 0
23 O 0
/ O 0
57 O 0
[ O 0
40 O 0
% O 0
] O 0
in O 0
the O 0
deep O 0
sedation O 0
group O 0
; O 0
P O 0
= O 0
. O 0
02 O 0
) O 0
, O 0
indicating O 0
that O 0
1 O 0
incident O 0
of O 0
delirium B-Disease 0
will O 0
be O 0
prevented O 0
for O 0
every O 0
4 O 0
. O 0
7 O 0
patients O 0
treated O 0
with O 0
light O 0
sedation O 0
. O 0

The O 0
mean O 0
+ O 0
/ O 0
- O 0
SD O 0
number O 0
of O 0
days O 0
of O 0
delirium B-Disease 0
during O 0
hospitalization O 0
was O 0
lower O 0
in O 0
the O 0
light O 0
sedation O 0
group O 0
than O 0
in O 0
the O 0
deep O 0
sedation O 0
group O 0
( O 0
0 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
5 O 0
days O 0
vs O 0
1 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
0 O 0
days O 0
; O 0
P O 0
= O 0
. O 0
01 O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
use O 0
of O 0
light O 0
propofol B-Chemical 0
sedation O 0
decreased O 0
the O 0
prevalence O 0
of O 0
postoperative B-Disease 0
delirium I-Disease 0
by O 0
50 O 0
% O 0
compared O 0
with O 0
deep O 0
sedation O 0
. O 0

Limiting O 0
depth O 0
of O 0
sedation O 0
during O 0
spinal O 0
anesthesia O 0
is O 0
a O 0
simple O 0
, O 0
safe O 0
, O 0
and O 0
cost O 0
- O 0
effective O 0
intervention O 0
for O 0
preventing O 0
postoperative B-Disease 0
delirium I-Disease 0
in O 0
elderly O 0
patients O 0
that O 0
could O 0
be O 0
widely O 0
and O 0
readily O 0
adopted O 0
. O 0

The O 0
protective O 0
role O 0
of O 0
Nrf2 O 0
in 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
Diabetic B-Disease 0
nephropathy I-Disease 0
is O 0
one O 0
of O 0
the O 0
major O 0
causes O 0
of O 0
renal B-Disease 0
failure I-Disease 0
, O 0
which O 0
is O 0
accompanied O 0
by O 0
the 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
. O 0

Nrf2 O 0
is O 0
the O 0
primary O 0
transcription O 0
factor O 0
that O 0
controls O 0
the O 0
antioxidant O 0
response O 0
essential O 0
for O 0
maintaining O 0
cellular O 0
redox O 0
homeostasis O 0
. O 0

Here O 0
, O 0
we O 0
report O 0
our O 0
findings O 0
demonstrating O 0
a O 0
protective O 0
role O 0
of O 0
Nrf2 O 0
against 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
We O 0
explore O 0
the O 0
protective O 0
role O 0
of O 0
Nrf2 O 0
against O 0
diabetic B-Disease 0
nephropathy I-Disease 0
using O 0
human O 0
kidney O 0
biopsy O 0
tissues O 0
from O 0
diabetic B-Disease 0
nephropathy I-Disease 0
patients O 0
, O 0
a O 0
streptozotocin B-Chemical 0
- O 0
induced O 0
diabetic B-Disease 0
nephropathy I-Disease 0
model O 0
in O 0
Nrf2 O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
, O 0
and O 0
cultured O 0
human O 0
mesangial O 0
cells O 0
. O 0

RESULTS O 0
: O 0
The O 0
glomeruli O 0
of O 0
human O 0
diabetic B-Disease 0
nephropathy I-Disease 0
patients O 0
were O 0
under O 0
oxidative O 0
stress O 0
and O 0
had O 0
elevated O 0
Nrf2 O 0
levels O 0
. O 0

In O 0
the O 0
animal O 0
study O 0
, O 0
Nrf2 O 0
was O 0
demonstrated O 0
to O 0
be O 0
crucial O 0
in O 0
ameliorating O 0
streptozotocin B-Chemical 0
- O 0
induced O 0
renal B-Disease 0
damage I-Disease 0
. O 0

This O 0
is O 0
evident O 0
by O 0
Nrf2 O 0
( O 0
- O 0
/ O 0
- O 0
) O 0
mice O 0
having O 0
higher O 0
ROS O 0
production O 0
and O 0
suffering O 0
from O 0
greater O 0
oxidative O 0
DNA O 0
damage O 0
and O 0
renal B-Disease 0
injury I-Disease 0
compared O 0
with O 0
Nrf2 O 0
( O 0
+ O 0
/ O 0
+ O 0
) O 0
mice O 0
. O 0

Mechanistic O 0
studies O 0
in O 0
both O 0
in O 0
vivo O 0
and O 0
in O 0
vitro O 0
systems O 0
showed O 0
that O 0
the O 0
Nrf2 O 0
- O 0
mediated O 0
protection O 0
against O 0
diabetic B-Disease 0
nephropathy I-Disease 0
is O 0
, O 0
at O 0
least O 0
, O 0
partially O 0
through O 0
inhibition O 0
of O 0
transforming O 0
growth O 0
factor O 0
- O 0
beta1 O 0
( O 0
TGF O 0
- O 0
beta1 O 0
) O 0
and O 0
reduction O 0
of O 0
extracellular O 0
matrix O 0
production O 0
. O 0

In O 0
human O 0
renal O 0
mesangial O 0
cells O 0
, O 0
high O 0
glucose B-Chemical 0
induced O 0
ROS O 0
production O 0
and O 0
activated O 0
expression O 0
of O 0
Nrf2 O 0
and O 0
its O 0
downstream O 0
genes O 0
. O 0

Furthermore O 0
, O 0
activation O 0
or O 0
overexpression O 0
of O 0
Nrf2 O 0
inhibited O 0
the O 0
promoter O 0
activity O 0
of O 0
TGF O 0
- O 0
beta1 O 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
manner O 0
, O 0
whereas O 0
knockdown O 0
of O 0
Nrf2 O 0
by O 0
siRNA O 0
enhanced O 0
TGF O 0
- O 0
beta1 O 0
transcription O 0
and O 0
fibronectin O 0
production O 0
. O 0

CONCLUSIONS O 0
: O 0
This O 0
work O 0
clearly O 0
indicates O 0
a O 0
protective O 0
role O 0
of O 0
Nrf2 O 0
in O 0
diabetic B-Disease 0
nephropathy I-Disease 0
, O 0
suggesting O 0
that O 0
dietary O 0
or O 0
therapeutic O 0
activation O 0
of O 0
Nrf2 O 0
could O 0
be O 0
used O 0
as O 0
a O 0
strategy O 0
to O 0
prevent O 0
or O 0
slow O 0
down O 0
the O 0
progression O 0
of O 0
diabetic B-Disease 0
nephropathy I-Disease 0
. O 0

Metformin B-Chemical 0
prevents O 0
experimental O 0
gentamicin B-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
by O 0
a O 0
mitochondria O 0
- O 0
dependent O 0
pathway O 0
. O 0

The O 0
antidiabetic O 0
drug O 0
metformin B-Chemical 0
can O 0
diminish O 0
apoptosis O 0
induced O 0
by O 0
oxidative O 0
stress O 0
in O 0
endothelial O 0
cells O 0
and O 0
prevent O 0
vascular B-Disease 0
dysfunction I-Disease 0
even O 0
in O 0
nondiabetic O 0
patients O 0
. O 0

Here O 0
we O 0
tested O 0
whether O 0
it O 0
has O 0
a O 0
beneficial O 0
effect O 0
in O 0
a O 0
rat O 0
model O 0
of O 0
gentamicin B-Chemical 0
toxicity B-Disease 0
. O 0

Mitochondrial O 0
analysis O 0
, O 0
respiration O 0
intensity O 0
, O 0
levels O 0
of O 0
reactive O 0
oxygen B-Chemical 0
species O 0
, O 0
permeability O 0
transition O 0
, O 0
and O 0
cytochrome O 0
c O 0
release O 0
were O 0
assessed O 0
3 O 0
and O 0
6 O 0
days O 0
after O 0
gentamicin B-Chemical 0
administration O 0
. O 0

Metformin B-Chemical 0
treatment O 0
fully O 0
blocked O 0
gentamicin B-Chemical 0
- O 0
mediated O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
. O 0

This O 0
was O 0
accompanied O 0
by O 0
a O 0
lower O 0
activity O 0
of 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
together O 0
with O 0
a O 0
decrease O 0
of O 0
lipid O 0
peroxidation O 0
and O 0
increase O 0
of O 0
antioxidant O 0
systems O 0
. O 0

Metformin B-Chemical 0
also O 0
protected O 0
the O 0
kidney O 0
from O 0
histological O 0
damage O 0
6 O 0
days O 0
after O 0
gentamicin B-Chemical 0
administration O 0
. O 0

These O 0
in O 0
vivo O 0
markers O 0
of O 0
kidney B-Disease 0
dysfunction I-Disease 0
and O 0
their O 0
correction O 0
by O 0
metformin B-Chemical 0
were O 0
complemented O 0
by O 0
in O 0
vitro O 0
studies O 0
of O 0
mitochondrial O 0
function O 0
. O 0

We O 0
found O 0
that O 0
gentamicin B-Chemical 0
treatment O 0
depleted O 0
respiratory O 0
components O 0
( O 0
cytochrome O 0
c O 0
, O 0
NADH O 0
) O 0
, O 0
probably O 0
due O 0
to O 0
the O 0
opening O 0
of O 0
mitochondrial O 0
transition O 0
pores O 0
. O 0

These O 0
injuries O 0
, O 0
partly O 0
mediated O 0
by O 0
a O 0
rise O 0
in O 0
reactive O 0
oxygen B-Chemical 0
species O 0
from O 0
the O 0
electron O 0
transfer O 0
chain O 0
, O 0
were O 0
significantly O 0
decreased O 0
by O 0
metformin B-Chemical 0
. O 0

Thus O 0
, O 0
our O 0
study O 0
suggests O 0
that O 0
pleiotropic O 0
effects O 0
of O 0
metformin B-Chemical 0
can O 0
lessen O 0
gentamicin B-Chemical 0
nephrotoxicity B-Disease 0
and O 0
improve O 0
mitochondrial O 0
homeostasis O 0
. O 0

Risk O 0
of O 0
nephropathy B-Disease 0
after O 0
consumption O 0
of O 0
nonionic O 0
contrast B-Chemical 0
media I-Chemical 0
by O 0
children O 0
undergoing O 0
cardiac O 0
angiography O 0
: O 0
a O 0
prospective O 0
study O 0
. O 0

Despite O 0
increasing O 0
reports O 0
on O 0
nonionic O 0
contrast B-Chemical 0
media I-Chemical 0
- O 0
induced O 0
nephropathy B-Disease 0
( O 0
CIN B-Disease 0
) O 0
in O 0
hospitalized O 0
adult O 0
patients O 0
during O 0
cardiac O 0
procedures O 0
, O 0
the O 0
studies O 0
in O 0
pediatrics O 0
are O 0
limited O 0
, O 0
with O 0
even O 0
less O 0
focus O 0
on O 0
possible O 0
predisposing O 0
factors O 0
and O 0
preventive O 0
measures O 0
for O 0
patients O 0
undergoing O 0
cardiac O 0
angiography O 0
. O 0

This O 0
prospective O 0
study O 0
determined O 0
the O 0
incidence O 0
of O 0
CIN B-Disease 0
for O 0
two O 0
nonionic O 0
contrast B-Chemical 0
media I-Chemical 0
( O 0
CM B-Chemical 0
) O 0
, O 0
iopromide B-Chemical 0
and O 0
iohexol B-Chemical 0
, O 0
among O 0
80 O 0
patients O 0
younger O 0
than O 0
18 O 0
years O 0
and O 0
compared O 0
the O 0
rates O 0
for O 0
this O 0
complication O 0
in O 0
relation O 0
to O 0
the O 0
type O 0
and O 0
dosage O 0
of O 0
CM B-Chemical 0
and O 0
the O 0
presence O 0
of O 0
cyanosis B-Disease 0
. O 0

The O 0
80 O 0
patients O 0
in O 0
the O 0
study O 0
consecutively O 0
received O 0
either O 0
iopromide B-Chemical 0
( O 0
group O 0
A O 0
, O 0
n O 0
= O 0
40 O 0
) O 0
or O 0
iohexol B-Chemical 0
( O 0
group O 0
B O 0
, O 0
n O 0
= O 0
40 O 0
) O 0
. O 0

Serum O 0
sodium B-Chemical 0
( O 0
Na B-Chemical 0
) O 0
, O 0
potassium B-Chemical 0
( O 0
K B-Chemical 0
) O 0
, O 0
and O 0
creatinine B-Chemical 0
( O 0
Cr B-Chemical 0
) O 0
were O 0
measured O 0
24 O 0
h O 0
before O 0
angiography O 0
as O 0
baseline O 0
values O 0
, O 0
then O 0
measured O 0
again O 0
at O 0
12 O 0
- O 0
, O 0
24 O 0
- O 0
, O 0
and O 0
48 O 0
- O 0
h O 0
intervals O 0
after O 0
CM B-Chemical 0
use O 0
. O 0

Urine O 0
samples O 0
for O 0
Na B-Chemical 0
and O 0
Cr B-Chemical 0
also O 0
were O 0
checked O 0
at O 0
the O 0
same O 0
intervals O 0
. O 0

Risk O 0
of O 0
renal B-Disease 0
failure I-Disease 0
, O 0
Injury B-Disease 0
to I-Disease 0
the I-Disease 0
kidney I-Disease 0
, O 0
Failure B-Disease 0
of I-Disease 0
kidney I-Disease 0
function I-Disease 0
, O 0
Loss B-Disease 0
of I-Disease 0
kidney I-Disease 0
function I-Disease 0
, O 0
and O 0
End O 0
- O 0
stage O 0
renal B-Disease 0
damage I-Disease 0
( O 0
RIFLE O 0
criteria O 0
) O 0
were O 0
used O 0
to O 0
define O 0
CIN B-Disease 0
and O 0
its O 0
incidence O 0
in O 0
the O 0
study O 0
population O 0
. O 0

Accordingly O 0
, O 0
among O 0
the O 0
15 O 0
CIN B-Disease 0
patients O 0
( O 0
18 O 0
. O 0
75 O 0
% O 0
) O 0
, O 0
7 O 0
. O 0
5 O 0
% O 0
of O 0
the O 0
patients O 0
in O 0
group O 0
A O 0
had O 0
increased O 0
risk O 0
and O 0
3 O 0
. O 0
75 O 0
% O 0
had O 0
renal B-Disease 0
injury I-Disease 0
, O 0
whereas O 0
5 O 0
% O 0
of O 0
group O 0
B O 0
had O 0
increased O 0
risk O 0
and O 0
2 O 0
. O 0
5 O 0
% O 0
had O 0
renal B-Disease 0
injury I-Disease 0
. O 0

Whereas O 0
33 O 0
. O 0
3 O 0
% O 0
of O 0
the O 0
patients O 0
with O 0
CIN B-Disease 0
were O 0
among O 0
those O 0
who O 0
received O 0
the O 0
proper O 0
dosage O 0
of O 0
CM B-Chemical 0
, O 0
the O 0
percentage O 0
increased O 0
to O 0
66 O 0
. O 0
6 O 0
% O 0
among O 0
those O 0
who O 0
received O 0
larger O 0
doses O 0
, O 0
with O 0
a O 0
significant O 0
difference O 0
in O 0
the O 0
incidence O 0
of O 0
CIN B-Disease 0
related O 0
to O 0
the O 0
different O 0
dosages O 0
of O 0
CM B-Chemical 0
( O 0
p O 0
= O 0
0 O 0
. O 0
014 O 0
) O 0
. O 0

Among O 0
the O 0
15 O 0
patients O 0
with O 0
CIN B-Disease 0
, O 0
6 O 0
had O 0
cyanotic O 0
congenital B-Disease 0
heart I-Disease 0
diseases I-Disease 0
, O 0
but O 0
the O 0
incidence O 0
did O 0
not O 0
differ O 0
significantly O 0
from O 0
that O 0
for O 0
the O 0
noncyanotic O 0
patients O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
243 O 0
) O 0
. O 0

Although O 0
clinically O 0
silent O 0
, O 0
CIN B-Disease 0
is O 0
not O 0
rare O 0
in O 0
pediatrics O 0
. O 0

The O 0
incidence O 0
depends O 0
on O 0
dosage O 0
but O 0
not O 0
on O 0
the O 0
type O 0
of O 0
consumed O 0
nonionic O 0
CM B-Chemical 0
, O 0
nor O 0
on O 0
the O 0
presence O 0
of O 0
cyanosis B-Disease 0
, O 0
and O 0
although O 0
CIN B-Disease 0
usually O 0
is O 0
reversible O 0
, O 0
more O 0
concern O 0
is O 0
needed O 0
for O 0
the O 0
prevention O 0
of O 0
such O 0
a O 0
complication O 0
in O 0
children O 0
. O 0

Renal O 0
function O 0
and O 0
hemodynamics O 0
during O 0
prolonged O 0
isoflurane B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
in O 0
humans O 0
. O 0

The O 0
effect O 0
of O 0
isoflurane B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
on O 0
glomerular O 0
function O 0
and O 0
renal O 0
blood O 0
flow O 0
was O 0
investigated O 0
in O 0
20 O 0
human O 0
subjects O 0
. O 0

Glomerular O 0
filtration O 0
rate O 0
( O 0
GFR O 0
) O 0
and O 0
effective O 0
renal O 0
plasma O 0
flow O 0
( O 0
ERPF O 0
) O 0
were O 0
measured O 0
by O 0
inulin O 0
and O 0
para B-Chemical 0
- I-Chemical 0
aminohippurate I-Chemical 0
( O 0
PAH B-Chemical 0
) O 0
clearance O 0
, O 0
respectively O 0
. O 0

Anesthesia O 0
was O 0
maintained O 0
with O 0
fentanyl B-Chemical 0
, O 0
nitrous B-Chemical 0
oxide I-Chemical 0
, O 0
oxygen B-Chemical 0
, O 0
and O 0
isoflurane B-Chemical 0
. O 0

Hypotension B-Disease 0
was O 0
induced O 0
for O 0
236 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
15 O 0
. O 0
1 O 0
min O 0
by O 0
increasing O 0
the O 0
isoflurane B-Chemical 0
inspired O 0
concentration O 0
to O 0
maintain O 0
a O 0
mean O 0
arterial O 0
pressure O 0
of O 0
59 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
4 O 0
mmHg O 0
. O 0

GFR O 0
and O 0
ERPF O 0
decreased O 0
with O 0
the O 0
induction O 0
of O 0
anesthesia O 0
but O 0
not O 0
significantly O 0
more O 0
during O 0
hypotension B-Disease 0
. O 0

Postoperatively O 0
, O 0
ERPF O 0
returned O 0
to O 0
preoperative O 0
values O 0
, O 0
whereas O 0
GFR O 0
was O 0
higher O 0
than O 0
preoperative O 0
values O 0
. O 0

Renal O 0
vascular O 0
resistance O 0
increased O 0
during O 0
anesthesia O 0
but O 0
decreased O 0
when O 0
hypotension B-Disease 0
was O 0
induced O 0
, O 0
allowing O 0
the O 0
maintenance O 0
of O 0
renal O 0
blood O 0
flow O 0
. O 0

We O 0
conclude O 0
that O 0
renal O 0
compensatory O 0
mechanisms O 0
are O 0
preserved O 0
during O 0
isoflurane B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
and O 0
that O 0
renal O 0
function O 0
and O 0
hemodynamics O 0
quickly O 0
return O 0
to O 0
normal O 0
when O 0
normotension O 0
is O 0
resumed O 0
. O 0

Brainstem B-Disease 0
dysgenesis I-Disease 0
in O 0
an O 0
infant O 0
prenatally O 0
exposed O 0
to O 0
cocaine B-Chemical 0
. O 0

Many O 0
authors O 0
described O 0
the O 0
effects O 0
on O 0
the O 0
fetus O 0
of O 0
maternal O 0
cocaine B-Disease 0
abuse I-Disease 0
during O 0
pregnancy O 0
. O 0

Vasoconstriction O 0
appears O 0
to O 0
be O 0
the O 0
common O 0
mechanism O 0
of O 0
action O 0
leading O 0
to O 0
a O 0
wide O 0
range O 0
of O 0
fetal B-Disease 0
anomalies I-Disease 0
. O 0

We O 0
report O 0
on O 0
an O 0
infant O 0
with O 0
multiple B-Disease 0
cranial I-Disease 0
- I-Disease 0
nerve I-Disease 0
involvement I-Disease 0
attributable O 0
to O 0
brainstem B-Disease 0
dysgenesis I-Disease 0
, O 0
born O 0
to O 0
a O 0
cocaine B-Disease 0
- I-Disease 0
addicted I-Disease 0
mother O 0
. O 0

A O 0
cross O 0
- O 0
sectional O 0
evaluation O 0
of O 0
the O 0
effect O 0
of O 0
risperidone B-Chemical 0
and O 0
selective O 0
serotonin B-Chemical 0
reuptake O 0
inhibitors O 0
on O 0
bone O 0
mineral O 0
density O 0
in O 0
boys O 0
. O 0

OBJECTIVE 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
effect O 0
of O 0
risperidone B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
on O 0
trabecular O 0
bone O 0
mineral O 0
density O 0
( O 0
BMD O 0
) O 0
in O 0
children O 0
and O 0
adolescents O 0
. O 0

METHOD O 0
: O 0
Medically O 0
healthy O 0
7 O 0
- O 0
to O 0
17 O 0
- O 0
year O 0
- O 0
old O 0
males O 0
chronically O 0
treated O 0
, O 0
in O 0
a O 0
naturalistic O 0
setting O 0
, O 0
with O 0
risperidone B-Chemical 0
were O 0
recruited O 0
for O 0
this O 0
cross O 0
- O 0
sectional O 0
study O 0
through O 0
child O 0
psychiatry O 0
outpatient O 0
clinics O 0
between O 0
November O 0
2005 O 0
and O 0
June O 0
2007 O 0
. O 0

Anthropometric O 0
measurements O 0
and O 0
laboratory O 0
testing O 0
were O 0
conducted O 0
. O 0

The O 0
clinical O 0
diagnoses O 0
were O 0
based O 0
on O 0
chart O 0
review O 0
, O 0
and O 0
developmental O 0
and O 0
treatment O 0
history O 0
was O 0
obtained O 0
from O 0
the O 0
medical O 0
record O 0
. O 0

Volumetric O 0
BMD O 0
of O 0
the O 0
ultradistal O 0
radius O 0
was O 0
measured O 0
using O 0
peripheral O 0
quantitative O 0
computed O 0
tomography O 0
, O 0
and O 0
areal O 0
BMD O 0
of O 0
the O 0
lumbar O 0
spine O 0
was O 0
estimated O 0
using O 0
dual O 0
- O 0
energy O 0
x O 0
- O 0
ray O 0
absorptiometry O 0
. O 0

RESULTS O 0
: O 0
Hyperprolactinemia B-Disease 0
was O 0
present O 0
in O 0
49 O 0
% O 0
of O 0
83 O 0
boys O 0
( O 0
n O 0
= O 0
41 O 0
) O 0
treated O 0
with O 0
risperidone B-Chemical 0
for O 0
a O 0
mean O 0
of O 0
2 O 0
. O 0
9 O 0
years O 0
. O 0

Serum O 0
testosterone B-Chemical 0
concentration O 0
increased O 0
with O 0
pubertal O 0
status O 0
but O 0
was O 0
not O 0
affected O 0
by O 0
hyperprolactinemia B-Disease 0
. O 0

As O 0
expected O 0
, O 0
bone O 0
mineral O 0
content O 0
and O 0
BMD O 0
increased O 0
with O 0
sexual O 0
maturity O 0
. O 0

After O 0
adjusting O 0
for O 0
the O 0
stage O 0
of O 0
sexual O 0
development O 0
and O 0
height O 0
and O 0
BMI O 0
z O 0
scores O 0
, O 0
serum O 0
prolactin O 0
was O 0
negatively O 0
associated O 0
with O 0
trabecular O 0
volumetric O 0
BMD O 0
at O 0
the O 0
ultradistal O 0
radius O 0
( O 0
P O 0
< O 0
. O 0
03 O 0
) O 0
. O 0

Controlling O 0
for O 0
relevant O 0
covariates O 0
, O 0
we O 0
also O 0
found O 0
treatment O 0
with O 0
selective O 0
serotonin B-Chemical 0
reuptake O 0
inhibitors O 0
( O 0
SSRIs O 0
) O 0
to O 0
be O 0
associated O 0
with O 0
lower O 0
trabecular O 0
BMD O 0
at O 0
the O 0
radius O 0
( O 0
P O 0
= O 0
. O 0
03 O 0
) O 0
and O 0
BMD O 0
z O 0
score O 0
at O 0
the O 0
lumbar O 0
spine O 0
( O 0
P O 0
< O 0
. O 0
05 O 0
) O 0
. O 0

These O 0
findings O 0
became O 0
more O 0
marked O 0
when O 0
the O 0
analysis O 0
was O 0
restricted O 0
to O 0
non O 0
- O 0
Hispanic O 0
white O 0
patients O 0
. O 0

Of O 0
13 O 0
documented O 0
fractures B-Disease 0
, O 0
3 O 0
occurred O 0
after O 0
risperidone B-Chemical 0
and O 0
SSRIs O 0
were O 0
started O 0
, O 0
and O 0
none O 0
occurred O 0
in O 0
patients O 0
with O 0
hyperprolactinemia B-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
This O 0
is O 0
the O 0
first O 0
study O 0
to O 0
link O 0
risperidone B-Chemical 0
- O 0
induced O 0
hyperprolactinemia B-Disease 0
and O 0
SSRI O 0
treatment O 0
to O 0
lower O 0
BMD O 0
in O 0
children O 0
and O 0
adolescents O 0
. O 0

Future O 0
research O 0
should O 0
evaluate O 0
the O 0
longitudinal O 0
course O 0
of O 0
this O 0
adverse O 0
event O 0
to O 0
determine O 0
its O 0
temporal O 0
stability O 0
and O 0
whether O 0
a O 0
higher O 0
fracture O 0
rate O 0
ensues O 0
. O 0

Fear O 0
- O 0
potentiated O 0
startle B-Disease 0
, O 0
but O 0
not O 0
light O 0
- O 0
enhanced O 0
startle B-Disease 0
, O 0
is O 0
enhanced O 0
by O 0
anxiogenic O 0
drugs O 0
. O 0

RATIONALE O 0
AND O 0
OBJECTIVES O 0
: O 0
The O 0
light O 0
- O 0
enhanced O 0
startle B-Disease 0
paradigm O 0
( O 0
LES O 0
) O 0
is O 0
suggested O 0
to O 0
model O 0
anxiety B-Disease 0
, O 0
because O 0
of O 0
the O 0
non O 0
- O 0
specific O 0
cue O 0
and O 0
the O 0
long O 0
- O 0
term O 0
effect O 0
. O 0

In O 0
contrast O 0
, O 0
the O 0
fear O 0
- O 0
potentiated O 0
startle B-Disease 0
( O 0
FPS O 0
) O 0
is O 0
suggested O 0
to O 0
model O 0
conditioned O 0
fear O 0
. O 0

However O 0
, O 0
the O 0
pharmacological O 0
profiles O 0
of O 0
these O 0
two O 0
paradigms O 0
are O 0
very O 0
similar O 0
. O 0

The O 0
present O 0
study O 0
investigated O 0
the O 0
effects O 0
of O 0
putative O 0
anxiogenic O 0
drugs O 0
on O 0
LES O 0
and O 0
FPS O 0
and O 0
aimed O 0
at O 0
determining O 0
the O 0
sensitivity O 0
of O 0
LES O 0
for O 0
anxiogenic O 0
drugs O 0
and O 0
to O 0
potentially O 0
showing O 0
a O 0
pharmacological O 0
differentiation O 0
between O 0
these O 0
two O 0
paradigms O 0
. O 0

METHODS O 0
: O 0
Male O 0
Wistar O 0
rats O 0
received O 0
each O 0
dose O 0
of O 0
the O 0
alpha O 0
( O 0
2 O 0
) O 0
- O 0
adrenoceptor O 0
antagonist O 0
yohimbine B-Chemical 0
( O 0
0 O 0
. O 0
25 O 0
- O 0
1 O 0
. O 0
0mg O 0
/ O 0
kg O 0
) O 0
, O 0
the O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
( O 0
2C O 0
) O 0
receptor O 0
agonist O 0
m B-Chemical 0
- I-Chemical 0
chlorophenylpiperazine I-Chemical 0
( O 0
mCPP B-Chemical 0
, O 0
0 O 0
. O 0
5 O 0
- O 0
2 O 0
. O 0
0mg O 0
/ O 0
kg O 0
) O 0
or O 0
the O 0
GABA B-Chemical 0
( O 0
A O 0
) O 0
inverse O 0
receptor O 0
agonist O 0
pentylenetetrazole B-Chemical 0
( O 0
PTZ B-Chemical 0
, O 0
3 O 0
- O 0
30mg O 0
/ O 0
kg O 0
) O 0
and O 0
were O 0
subsequently O 0
tested O 0
in O 0
either O 0
LES O 0
or O 0
FPS O 0
. O 0

RESULTS O 0
: O 0
None O 0
of O 0
the O 0
drugs O 0
enhanced O 0
LES O 0
, O 0
whereas O 0
mCPP B-Chemical 0
increased O 0
percentage O 0
FPS O 0
and O 0
yohimbine B-Chemical 0
increased O 0
absolute O 0
FPS O 0
values O 0
. O 0

Furthermore O 0
, O 0
yohimbine B-Chemical 0
increased O 0
baseline O 0
startle B-Disease 0
amplitude O 0
in O 0
the O 0
LES O 0
, O 0
while O 0
mCPP B-Chemical 0
suppressed O 0
baseline O 0
startle B-Disease 0
in O 0
both O 0
the O 0
LES O 0
and O 0
FPS O 0
and O 0
PTZ B-Chemical 0
suppressed O 0
baseline O 0
startle B-Disease 0
in O 0
the O 0
FPS O 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
contrast O 0
to O 0
findings O 0
in O 0
the O 0
FPS O 0
paradigm O 0
, O 0
none O 0
of O 0
the O 0
drugs O 0
were O 0
able O 0
to O 0
exacerbate O 0
the O 0
LES O 0
response O 0
. O 0

Thus O 0
, O 0
a O 0
clear O 0
pharmacological O 0
differentiation O 0
was O 0
found O 0
between O 0
LES O 0
and O 0
FPS O 0
. O 0

Rosaceiform O 0
dermatitis B-Disease 0
associated O 0
with O 0
topical O 0
tacrolimus B-Chemical 0
treatment O 0
. O 0

We O 0
describe O 0
herein O 0
3 O 0
patients O 0
who O 0
developed O 0
rosacea B-Disease 0
- O 0
like O 0
dermatitis B-Disease 0
eruptions B-Disease 0
while O 0
using O 0
0 O 0
. O 0
03 O 0
% O 0
or O 0
0 O 0
. O 0
1 O 0
% O 0
tacrolimus B-Chemical 0
ointment O 0
for O 0
facial B-Disease 0
dermatitis I-Disease 0
. O 0

Skin O 0
biopsy O 0
specimens O 0
showed O 0
telangiectasia B-Disease 0
and O 0
noncaseating O 0
epithelioid O 0
granulomatous O 0
tissue O 0
formation O 0
in O 0
the O 0
papillary O 0
to O 0
mid O 0
dermis O 0
. O 0

Continuous O 0
topical O 0
use O 0
of O 0
immunomodulators O 0
such O 0
as O 0
tacrolimus B-Chemical 0
or O 0
pimecrolimus B-Chemical 0
should O 0
be O 0
regarded O 0
as O 0
a O 0
potential O 0
cause O 0
of O 0
rosaceiform O 0
dermatitis B-Disease 0
, O 0
although O 0
many O 0
cases O 0
have O 0
not O 0
been O 0
reported O 0
. O 0

Coenzyme B-Chemical 0
Q10 I-Chemical 0
treatment O 0
ameliorates O 0
acute O 0
cisplatin B-Chemical 0
nephrotoxicity B-Disease 0
in O 0
mice O 0
. O 0

The O 0
nephroprotective O 0
effect O 0
of O 0
coenzyme B-Chemical 0
Q10 I-Chemical 0
was O 0
investigated O 0
in O 0
mice O 0
with O 0
acute B-Disease 0
renal I-Disease 0
injury I-Disease 0
induced O 0
by O 0
a O 0
single O 0
i O 0
. O 0
p O 0
. O 0
injection O 0
of O 0
cisplatin B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
. O 0

Coenzyme B-Chemical 0
Q10 I-Chemical 0
treatment O 0
( O 0
10 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
was O 0
applied O 0
for O 0
6 O 0
consecutive O 0
days O 0
, O 0
starting O 0
1 O 0
day O 0
before O 0
cisplatin B-Chemical 0
administration O 0
. O 0

Coenzyme B-Chemical 0
Q10 I-Chemical 0
significantly O 0
reduced O 0
blood B-Chemical 0
urea I-Chemical 0
nitrogen I-Chemical 0
and O 0
serum O 0
creatinine B-Chemical 0
levels O 0
which O 0
were O 0
increased O 0
by O 0
cisplatin B-Chemical 0
. O 0

Coenzyme B-Chemical 0
Q10 I-Chemical 0
significantly O 0
compensated O 0
deficits O 0
in O 0
the O 0
antioxidant O 0
defense O 0
mechanisms O 0
( O 0
reduced B-Chemical 0
glutathione I-Chemical 0
level O 0
and O 0
superoxide B-Chemical 0
dismutase O 0
activity O 0
) O 0
, O 0
suppressed O 0
lipid O 0
peroxidation O 0
, O 0
decreased O 0
the O 0
elevations O 0
of O 0
tumor B-Disease 0
necrosis B-Disease 0
factor O 0
- O 0
alpha O 0
, O 0
nitric B-Chemical 0
oxide I-Chemical 0
and O 0
platinum B-Chemical 0
ion O 0
concentration O 0
, O 0
and O 0
attenuated O 0
the O 0
reductions O 0
of O 0
selenium B-Chemical 0
and O 0
zinc B-Chemical 0
ions O 0
in O 0
renal O 0
tissue O 0
resulted O 0
from O 0
cisplatin B-Chemical 0
administration O 0
. O 0

Also O 0
, O 0
histopathological O 0
renal B-Disease 0
tissue I-Disease 0
damage I-Disease 0
mediated O 0
by O 0
cisplatin B-Chemical 0
was O 0
ameliorated O 0
by O 0
coenzyme B-Chemical 0
Q10 I-Chemical 0
treatment O 0
. O 0

Immunohistochemical O 0
analysis O 0
revealed O 0
that O 0
coenzyme B-Chemical 0
Q10 I-Chemical 0
significantly O 0
decreased O 0
the O 0
cisplatin B-Chemical 0
- O 0
induced O 0
overexpression O 0
of O 0
inducible O 0
nitric B-Chemical 0
oxide I-Chemical 0
synthase O 0
, O 0
nuclear O 0
factor O 0
- O 0
kappaB O 0
, O 0
caspase O 0
- O 0
3 O 0
and O 0
p53 O 0
in O 0
renal O 0
tissue O 0
. O 0

It O 0
was O 0
concluded O 0
that O 0
coenzyme B-Chemical 0
Q10 I-Chemical 0
represents O 0
a O 0
potential O 0
therapeutic O 0
option O 0
to O 0
protect O 0
against O 0
acute O 0
cisplatin B-Chemical 0
nephrotoxicity B-Disease 0
commonly O 0
encountered O 0
in O 0
clinical O 0
practice O 0
. O 0

Reversible O 0
cholestasis B-Disease 0
with O 0
bile B-Disease 0
duct I-Disease 0
injury I-Disease 0
following O 0
azathioprine B-Chemical 0
therapy O 0
. O 0

A O 0
case O 0
report O 0
. O 0

A O 0
67 O 0
- O 0
year O 0
- O 0
old O 0
patient O 0
, O 0
with O 0
primary O 0
polymyositis B-Disease 0
and O 0
without O 0
previous O 0
evidence O 0
of O 0
liver B-Disease 0
disease I-Disease 0
, O 0
developed O 0
clinical O 0
and O 0
biochemical O 0
features O 0
of O 0
severe O 0
cholestasis B-Disease 0
3 O 0
months O 0
after O 0
initiation O 0
of O 0
azathioprine B-Chemical 0
therapy O 0
. O 0

Liver O 0
biopsy O 0
showed O 0
cholestasis B-Disease 0
with O 0
both O 0
cytological O 0
and O 0
architectural O 0
alterations O 0
of O 0
interlobular O 0
bile O 0
ducts O 0
. O 0

Azathioprine B-Chemical 0
withdrawal O 0
resulted O 0
after O 0
7 O 0
weeks O 0
in O 0
the O 0
resolution O 0
of O 0
clinical O 0
and O 0
biochemical O 0
abnormalities O 0
. O 0

It O 0
is O 0
believed O 0
that O 0
this O 0
is O 0
the O 0
first O 0
reported O 0
case O 0
of O 0
reversible O 0
azathioprine B-Chemical 0
- O 0
induced O 0
cholestasis B-Disease 0
associated O 0
with O 0
histological O 0
evidence O 0
of O 0
bile B-Disease 0
duct I-Disease 0
injury I-Disease 0
. O 0

Dopamine B-Chemical 0
is O 0
not O 0
essential O 0
for O 0
the O 0
development O 0
of O 0
methamphetamine B-Chemical 0
- O 0
induced O 0
neurotoxicity B-Disease 0
. O 0

It O 0
is O 0
widely O 0
believed O 0
that O 0
dopamine B-Chemical 0
( O 0
DA B-Chemical 0
) O 0
mediates O 0
methamphetamine B-Chemical 0
( O 0
METH B-Chemical 0
) O 0
- O 0
induced O 0
toxicity B-Disease 0
to O 0
brain O 0
dopaminergic O 0
neurons O 0
, O 0
because O 0
drugs O 0
that O 0
interfere O 0
with O 0
DA B-Chemical 0
neurotransmission O 0
decrease O 0
toxicity B-Disease 0
, O 0
whereas O 0
drugs O 0
that O 0
increase O 0
DA B-Chemical 0
neurotransmission O 0
enhance O 0
toxicity B-Disease 0
. O 0

However O 0
, O 0
temperature O 0
effects O 0
of O 0
drugs O 0
that O 0
have O 0
been O 0
used O 0
to O 0
manipulate O 0
brain O 0
DA B-Chemical 0
neurotransmission O 0
confound O 0
interpretation O 0
of O 0
the O 0
data O 0
. O 0

Here O 0
we O 0
show O 0
that O 0
the O 0
recently O 0
reported O 0
ability O 0
of O 0
L B-Chemical 0
- I-Chemical 0
dihydroxyphenylalanine I-Chemical 0
to O 0
reverse O 0
the O 0
protective O 0
effect O 0
of O 0
alpha B-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
- I-Chemical 0
para I-Chemical 0
- I-Chemical 0
tyrosine I-Chemical 0
on O 0
METH B-Chemical 0
- O 0
induced O 0
DA B-Chemical 0
neurotoxicity B-Disease 0
is O 0
also O 0
confounded O 0
by O 0
drug O 0
effects O 0
on O 0
body O 0
temperature O 0
. O 0

Further O 0
, O 0
we O 0
show O 0
that O 0
mice O 0
genetically O 0
engineered O 0
to O 0
be O 0
deficient O 0
in O 0
brain O 0
DA B-Chemical 0
develop O 0
METH B-Chemical 0
neurotoxicity B-Disease 0
, O 0
as O 0
long O 0
as O 0
the O 0
thermic O 0
effects O 0
of O 0
METH B-Chemical 0
are O 0
preserved O 0
. O 0

In O 0
addition O 0
, O 0
we O 0
demonstrate O 0
that O 0
mice O 0
genetically O 0
engineered O 0
to O 0
have O 0
unilateral O 0
brain O 0
DA B-Chemical 0
deficits O 0
develop O 0
METH B-Chemical 0
- O 0
induced O 0
dopaminergic B-Disease 0
deficits I-Disease 0
that O 0
are O 0
of O 0
comparable O 0
magnitude O 0
on O 0
both O 0
sides O 0
of O 0
the O 0
brain O 0
. O 0

Taken O 0
together O 0
, O 0
these O 0
findings O 0
demonstrate O 0
that O 0
DA B-Chemical 0
is O 0
not O 0
essential O 0
for O 0
the O 0
development O 0
of O 0
METH B-Chemical 0
- O 0
induced O 0
dopaminergic O 0
neurotoxicity B-Disease 0
and O 0
suggest O 0
that O 0
mechanisms O 0
independent O 0
of O 0
DA B-Chemical 0
warrant O 0
more O 0
intense O 0
investigation O 0
. O 0

Swallowing O 0
- O 0
induced O 0
atrial B-Disease 0
tachyarrhythmia I-Disease 0
triggered O 0
by O 0
salbutamol B-Chemical 0
: 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

CASE O 0
: O 0
A O 0
49 O 0
- O 0
year O 0
- O 0
old O 0
patient O 0
experienced O 0
chest O 0
discomfort O 0
while O 0
swallowing O 0
. O 0

On O 0
electrocardiogram O 0
, O 0
episodes O 0
of O 0
atrial B-Disease 0
tachyarrhythmia I-Disease 0
were O 0
recorded O 0
immediately O 0
after O 0
swallowing O 0
; O 0
24 O 0
- O 0
hour O 0
Holter O 0
monitoring O 0
recorded O 0
several O 0
events O 0
. O 0

The O 0
arrhythmia B-Disease 0
resolved O 0
after O 0
therapy O 0
with O 0
atenolol B-Chemical 0
, O 0
but O 0
recurred O 0
a O 0
year O 0
later O 0
. O 0

The O 0
patient O 0
noticed O 0
that O 0
before O 0
these O 0
episodes O 0
he O 0
had O 0
been O 0
using O 0
an O 0
inhalator O 0
of O 0
salbutamol B-Chemical 0
. O 0

After O 0
stopping O 0
the O 0
beta O 0
- O 0
agonist O 0
, O 0
and O 0
after O 0
a O 0
week O 0
with O 0
the O 0
atenolol B-Chemical 0
, O 0
the O 0
arrhythmia B-Disease 0
disappeared O 0
. O 0

DISCUSSION O 0
: O 0
Swallowing O 0
- O 0
induced O 0
atrial B-Disease 0
tachyarrhythmia I-Disease 0
( O 0
SIAT B-Disease 0
) O 0
is O 0
a O 0
rare O 0
phenomenon O 0
. O 0

Fewer O 0
than O 0
50 O 0
cases O 0
of O 0
SIAT B-Disease 0
have O 0
been O 0
described O 0
in O 0
the O 0
literature O 0
. O 0

This O 0
article O 0
summarizes O 0
all O 0
the O 0
cases O 0
published O 0
, O 0
creating O 0
a O 0
comprehensive O 0
review O 0
of O 0
the O 0
current O 0
knowledge O 0
and O 0
approach O 0
to O 0
SIAT B-Disease 0
. O 0

It O 0
discusses O 0
demographics O 0
, O 0
clinical O 0
characteristics O 0
and O 0
types O 0
of O 0
arrhythmia B-Disease 0
, O 0
postulated O 0
mechanisms O 0
of O 0
SIAT B-Disease 0
, O 0
and O 0
different O 0
treatment O 0
possibilities O 0
such O 0
as O 0
medications O 0
, O 0
surgery O 0
, O 0
and O 0
radiofrequency O 0
catheter O 0
ablation O 0
( O 0
RFCA O 0
) O 0
. O 0

CONCLUSION O 0
: O 0
Salbutamol B-Chemical 0
is O 0
presented O 0
here O 0
as O 0
a O 0
possible O 0
trigger O 0
for O 0
SIAT B-Disease 0
. O 0

Although O 0
it O 0
is O 0
difficult O 0
to O 0
define O 0
causality O 0
in O 0
a O 0
case O 0
report O 0
, O 0
it O 0
is O 0
logical O 0
to O 0
think O 0
that O 0
a O 0
beta O 0
- O 0
agonist O 0
like O 0
salbutamol B-Chemical 0
( O 0
known O 0
to O 0
induce O 0
tachycardia B-Disease 0
) O 0
may O 0
be O 0
the O 0
trigger O 0
of O 0
adrenergic O 0
reflexes O 0
originating O 0
in O 0
the O 0
esophagus O 0
while O 0
swallowing O 0
and O 0
that O 0
a O 0
beta O 0
- O 0
blocker O 0
such O 0
as O 0
atenolol B-Chemical 0
( O 0
that O 0
blocks O 0
the O 0
adrenergic O 0
activity O 0
) O 0
may O 0
relieve O 0
it O 0
. O 0

The O 0
ability O 0
of O 0
insulin O 0
treatment O 0
to O 0
reverse O 0
or O 0
prevent O 0
the O 0
changes O 0
in O 0
urinary O 0
bladder O 0
function O 0
caused O 0
by O 0
streptozotocin B-Chemical 0
- O 0
induced O 0
diabetes B-Disease 0
mellitus I-Disease 0
. O 0

1 O 0
. O 0

The O 0
effects O 0
of O 0
insulin O 0
treatment O 0
on O 0
in O 0
vivo O 0
and O 0
in O 0
vitro O 0
urinary O 0
bladder O 0
function O 0
in O 0
streptozotocin B-Chemical 0
- O 0
diabetic B-Disease 0
rats O 0
were O 0
investigated O 0
. O 0

2 O 0
. O 0

Diabetes B-Disease 0
of O 0
2 O 0
months O 0
duration O 0
resulted O 0
in O 0
decreases O 0
in O 0
body O 0
weight O 0
and O 0
increases O 0
in O 0
fluid O 0
consumption O 0
, O 0
urine O 0
volume O 0
, O 0
frequency O 0
of O 0
micturition O 0
, O 0
and O 0
average O 0
volume O 0
per O 0
micturition O 0
; O 0
effects O 0
which O 0
were O 0
prevented O 0
by O 0
insulin O 0
treatment O 0
. O 0

3 O 0
. O 0

Insulin O 0
treatment O 0
also O 0
prevented O 0
the O 0
increases O 0
in O 0
contractile O 0
responses O 0
of O 0
bladder O 0
body O 0
strips O 0
from O 0
diabetic B-Disease 0
rats O 0
to O 0
nerve O 0
stimulation O 0
, O 0
ATP B-Chemical 0
, O 0
and O 0
bethanechol B-Chemical 0
. O 0

4 O 0
. O 0

Diabetes B-Disease 0
of O 0
4 O 0
months O 0
duration O 0
also O 0
resulted O 0
in O 0
decreases O 0
in O 0
body O 0
weight O 0
, O 0
and O 0
increases O 0
in O 0
fluid O 0
consumption O 0
, O 0
urine O 0
volume O 0
, O 0
frequency O 0
of O 0
micturition O 0
, O 0
and O 0
average O 0
volume O 0
per O 0
micturition O 0
, O 0
effects O 0
which O 0
were O 0
reversed O 0
by O 0
insulin O 0
treatment O 0
for O 0
the O 0
final O 0
2 O 0
months O 0
of O 0
the O 0
study O 0
. O 0

5 O 0
. O 0

Insulin O 0
treatment O 0
reversed O 0
the O 0
increases O 0
in O 0
contractile O 0
responses O 0
of O 0
bladder O 0
body O 0
strips O 0
from O 0
diabetic B-Disease 0
rats O 0
to O 0
nerve O 0
stimulation O 0
, O 0
ATP B-Chemical 0
, O 0
and O 0
bethanechol B-Chemical 0
. O 0

6 O 0
. O 0

The O 0
data O 0
indicate O 0
that O 0
the O 0
effects O 0
of O 0
streptozotocin B-Chemical 0
- O 0
induced O 0
diabetes B-Disease 0
on O 0
urinary O 0
bladder O 0
function O 0
are O 0
both O 0
prevented O 0
and O 0
reversed O 0
by O 0
insulin O 0
treatment O 0
. O 0

Glutamatergic O 0
neurotransmission O 0
mediated O 0
by O 0
NMDA B-Chemical 0
receptors O 0
in O 0
the O 0
inferior O 0
colliculus O 0
can O 0
modulate O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
. O 0

The O 0
inferior O 0
colliculus O 0
( O 0
IC O 0
) O 0
is O 0
primarily O 0
involved O 0
in O 0
the O 0
processing O 0
of O 0
auditory O 0
information O 0
, O 0
but O 0
it O 0
is O 0
distinguished O 0
from O 0
other O 0
auditory O 0
nuclei O 0
in O 0
the O 0
brainstem O 0
by O 0
its O 0
connections O 0
with O 0
structures O 0
of O 0
the O 0
motor O 0
system O 0
. O 0

Functional O 0
evidence O 0
relating O 0
the O 0
IC O 0
to O 0
motor O 0
behavior O 0
derives O 0
from O 0
experiments O 0
showing O 0
that O 0
activation O 0
of O 0
the O 0
IC O 0
by O 0
electrical O 0
stimulation O 0
or O 0
excitatory O 0
amino B-Chemical 0
acid I-Chemical 0
microinjection O 0
causes O 0
freezing O 0
, O 0
escape O 0
- O 0
like O 0
behavior O 0
, O 0
and O 0
immobility O 0
. O 0

However O 0
, O 0
the O 0
nature O 0
of O 0
this O 0
immobility O 0
is O 0
still O 0
unclear O 0
. O 0

The O 0
present O 0
study O 0
examined O 0
the O 0
influence O 0
of O 0
excitatory O 0
amino B-Chemical 0
acid I-Chemical 0
- O 0
mediated O 0
mechanisms O 0
in O 0
the O 0
IC O 0
on O 0
the O 0
catalepsy B-Disease 0
induced O 0
by O 0
the O 0
dopamine B-Chemical 0
receptor O 0
blocker O 0
haloperidol B-Chemical 0
administered O 0
systemically O 0
( O 0
1 O 0
or O 0
0 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
in O 0
rats O 0
. O 0

Haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
was O 0
challenged O 0
with O 0
prior O 0
intracollicular O 0
microinjections O 0
of O 0
glutamate B-Chemical 0
NMDA B-Chemical 0
receptor O 0
antagonists O 0
, O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
( O 0
15 O 0
or O 0
30 O 0
mmol O 0
/ O 0
0 O 0
. O 0
5 O 0
microl O 0
) O 0
and O 0
AP7 B-Chemical 0
( O 0
10 O 0
or O 0
20 O 0
nmol O 0
/ O 0
0 O 0
. O 0
5 O 0
microl O 0
) O 0
, O 0
or O 0
of O 0
the O 0
NMDA B-Chemical 0
receptor O 0
agonist 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
20 O 0
or O 0
30 O 0
nmol O 0
/ O 0
0 O 0
. O 0
5 O 0
microl O 0
) O 0
. O 0

The O 0
results O 0
showed O 0
that O 0
intracollicular O 0
microinjection O 0
of O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
and O 0
AP7 B-Chemical 0
previous O 0
to O 0
systemic O 0
injections O 0
of O 0
haloperidol B-Chemical 0
significantly O 0
attenuated O 0
the O 0
catalepsy B-Disease 0
, O 0
as O 0
indicated O 0
by O 0
a O 0
reduced O 0
latency O 0
to O 0
step O 0
down O 0
from O 0
a O 0
horizontal O 0
bar O 0
. O 0

Accordingly O 0
, O 0
intracollicular O 0
microinjection O 0
of O 0
NMDA B-Chemical 0
increased O 0
the O 0
latency O 0
to O 0
step O 0
down O 0
the O 0
bar O 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
glutamate B-Chemical 0
- O 0
mediated O 0
mechanisms O 0
in O 0
the O 0
neural O 0
circuits O 0
at O 0
the O 0
IC O 0
level O 0
influence O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
and O 0
participate O 0
in O 0
the O 0
regulation O 0
of O 0
motor O 0
activity O 0
. O 0

Severe O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
patient O 0
on O 0
amiodarone B-Chemical 0
presenting O 0
with O 0
myxedemic B-Disease 0
coma I-Disease 0
: O 0
a O 0
case O 0
report O 0
. O 0

This O 0
is O 0
a O 0
case O 0
report O 0
of O 0
myxedema B-Disease 0
coma I-Disease 0
secondary O 0
to O 0
amiodarone B-Chemical 0
- O 0
induced O 0
hypothyroidism B-Disease 0
in O 0
a O 0
patient O 0
with O 0
severe O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
( O 0
CHF B-Disease 0
) O 0
. O 0

To O 0
our O 0
knowledge O 0
and O 0
after O 0
reviewing O 0
the O 0
literature O 0
there O 0
is O 0
one O 0
case O 0
report O 0
of O 0
myxedema B-Disease 0
coma I-Disease 0
during O 0
long O 0
term O 0
amiodarone B-Chemical 0
therapy O 0
. O 0

Myxedema B-Disease 0
coma I-Disease 0
is O 0
a O 0
life O 0
threatening O 0
condition O 0
that O 0
carries O 0
a O 0
mortality O 0
reaching O 0
as O 0
high O 0
as O 0
20 O 0
% O 0
with O 0
treatment O 0
. O 0

The O 0
condition O 0
is O 0
treated O 0
with O 0
intravenous O 0
thyroxine B-Chemical 0
( O 0
T4 B-Chemical 0
) O 0
or O 0
intravenous O 0
tri B-Chemical 0
- I-Chemical 0
iodo I-Chemical 0
- I-Chemical 0
thyronine I-Chemical 0
( O 0
T3 B-Chemical 0
) O 0
. O 0

Patients O 0
with O 0
CHF B-Disease 0
on O 0
amiodarone B-Chemical 0
may O 0
suffer O 0
serious O 0
morbidity O 0
and O 0
mortality O 0
from O 0
hypothyroidism B-Disease 0
, O 0
and O 0
thus O 0
may O 0
deserve O 0
closer O 0
follow O 0
up O 0
for O 0
thyroid O 0
stimulating O 0
hormone O 0
( O 0
TSH O 0
) O 0
levels O 0
. O 0

This O 0
case O 0
report O 0
carries O 0
an O 0
important O 0
clinical O 0
application O 0
given O 0
the O 0
frequent O 0
usage O 0
of O 0
amiodarone B-Chemical 0
among O 0
CHF B-Disease 0
patients O 0
. O 0

The O 0
myriad O 0
clinical O 0
presentation O 0
of O 0
myxedema B-Disease 0
coma I-Disease 0
and O 0
its O 0
serious O 0
morbidity O 0
and O 0
mortality O 0
stresses O 0
the O 0
need O 0
to O 0
suspect O 0
this O 0
clinical O 0
syndrome O 0
among O 0
CHF B-Disease 0
patients O 0
presenting O 0
with O 0
hypotension B-Disease 0
, O 0
weakness B-Disease 0
or O 0
other O 0
unexplained O 0
symptoms O 0
. O 0

Effects O 0
of O 0
active O 0
constituents O 0
of O 0
Crocus O 0
sativus O 0
L O 0
. O 0
, O 0
crocin B-Chemical 0
on O 0
streptozocin B-Chemical 0
- O 0
induced O 0
model O 0
of O 0
sporadic O 0
Alzheimer B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
in O 0
male O 0
rats O 0
. O 0

BACKGROUND O 0
: O 0
The O 0
involvement O 0
of O 0
water O 0
- O 0
soluble O 0
carotenoids B-Chemical 0
, O 0
crocins B-Chemical 0
, O 0
as O 0
the O 0
main O 0
and O 0
active O 0
components O 0
of O 0
Crocus O 0
sativus O 0
L O 0
. O 0
extract O 0
in O 0
learning O 0
and O 0
memory O 0
processes O 0
has O 0
been O 0
proposed 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
crocins B-Chemical 0
on O 0
sporadic O 0
Alzheimer B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
induced O 0
by O 0
intracerebroventricular O 0
( O 0
icv O 0
) O 0
streptozocin B-Chemical 0
( O 0
STZ B-Chemical 0
) O 0
in O 0
male O 0
rats O 0
was O 0
investigated O 0
. O 0

METHODS O 0
: O 0
Male O 0
adult O 0
Wistar O 0
rats O 0
( O 0
n O 0
= O 0
90 O 0
and O 0
260 O 0
- O 0
290 O 0
g O 0
) O 0
were O 0
divided O 0
into O 0
1 O 0
, O 0
control O 0
; O 0
2 O 0
and O 0
3 O 0
, O 0
crocins B-Chemical 0
( O 0
15 O 0
and O 0
30 O 0
mg O 0
/ O 0
kg O 0
) O 0
; O 0
4 O 0
, O 0
STZ B-Chemical 0
; O 0
5 O 0
and O 0
6 O 0
, O 0
STZ B-Chemical 0
+ O 0
crocins B-Chemical 0
( O 0
15 O 0
and O 0
30 O 0
mg O 0
/ O 0
kg O 0
) O 0
groups O 0
. O 0

In O 0
Alzheimer B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
groups O 0
, O 0
rats O 0
were O 0
injected O 0
with O 0
STZ B-Chemical 0
- O 0
icv O 0
bilaterally O 0
( O 0
3 O 0
mg O 0
/ O 0
kg O 0
) O 0
in O 0
first O 0
day O 0
and O 0
3 O 0
days O 0
later O 0
, O 0
a O 0
similar O 0
STZ B-Chemical 0
- O 0
icv O 0
application O 0
was O 0
repeated O 0
. O 0

In O 0
STZ B-Chemical 0
+ O 0
crocin B-Chemical 0
animal O 0
groups O 0
, O 0
crocin B-Chemical 0
was O 0
applied O 0
in O 0
doses O 0
of O 0
15 O 0
and 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
one O 0
day O 0
pre O 0
- O 0
surgery O 0
and O 0
continued O 0
for O 0
three O 0
weeks O 0
. O 0

Prescription O 0
of O 0
crocin B-Chemical 0
in O 0
each O 0
dose O 0
was O 0
repeated O 0
once O 0
for O 0
two O 0
days O 0
. O 0

However O 0
, O 0
the O 0
learning O 0
and O 0
memory O 0
performance O 0
was O 0
assessed O 0
using O 0
passive O 0
avoidance O 0
paradigm O 0
, O 0
and O 0
for O 0
spatial O 0
cognition O 0
evaluation O 0
, O 0
Y O 0
- O 0
maze O 0
task O 0
was O 0
used O 0
. O 0

RESULTS O 0
: O 0
It O 0
was O 0
found O 0
out O 0
that O 0
crocin B-Chemical 0
( O 0
30 O 0
mg O 0
/ O 0
kg O 0
) O 0
- O 0
treated O 0
STZ B-Chemical 0
- O 0
injected O 0
rats O 0
show O 0
higher O 0
correct O 0
choices O 0
and O 0
lower O 0
errors O 0
in O 0
Y O 0
- O 0
maze O 0
than O 0
vehicle O 0
- O 0
treated O 0
STZ B-Chemical 0
- O 0
injected O 0
rats O 0
. O 0

In O 0
addition O 0
, O 0
crocin B-Chemical 0
in O 0
the O 0
mentioned O 0
dose O 0
could O 0
significantly O 0
attenuated O 0
learning B-Disease 0
and I-Disease 0
memory I-Disease 0
impairment I-Disease 0
in O 0
treated O 0
STZ B-Chemical 0
- O 0
injected O 0
group O 0
in O 0
passive O 0
avoidance O 0
test O 0
. O 0

CONCLUSION O 0
: O 0
Therefore O 0
, O 0
these O 0
results O 0
demonstrate O 0
the O 0
effectiveness O 0
of O 0
crocin B-Chemical 0
( O 0
30 O 0
mg O 0
/ O 0
kg O 0
) O 0
in O 0
antagonizing O 0
the O 0
cognitive B-Disease 0
deficits I-Disease 0
caused O 0
by O 0
STZ B-Chemical 0
- O 0
icv O 0
in O 0
rats O 0
and O 0
its O 0
potential O 0
in O 0
the O 0
treatment O 0
of O 0
neurodegenerative B-Disease 0
diseases I-Disease 0
such O 0
as O 0
Alzheimer B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

Serotonin B-Chemical 0
6 O 0
receptor O 0
gene O 0
is O 0
associated O 0
with O 0
methamphetamine B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
in O 0
a O 0
Japanese O 0
population O 0
. O 0

BACKGROUND O 0
: O 0
Altered O 0
serotonergic O 0
neural O 0
transmission O 0
is O 0
hypothesized O 0
to O 0
be O 0
a O 0
susceptibility O 0
factor O 0
for O 0
psychotic B-Disease 0
disorders I-Disease 0
such O 0
as O 0
schizophrenia B-Disease 0
. O 0

The O 0
serotonin B-Chemical 0
6 O 0
( O 0
5 B-Chemical 0
- I-Chemical 0
HT6 I-Chemical 0
) O 0
receptor O 0
is O 0
therapeutically O 0
targeted O 0
by O 0
several O 0
second O 0
generation O 0
antipsychotics O 0
, O 0
such O 0
as O 0
clozapine B-Chemical 0
and O 0
olanzapine B-Chemical 0
, O 0
and O 0
d B-Chemical 0
- I-Chemical 0
amphetamine I-Chemical 0
- O 0
induced O 0
hyperactivity B-Disease 0
in O 0
rats O 0
is O 0
corrected O 0
with O 0
the O 0
use O 0
of O 0
a O 0
selective O 0
5 B-Chemical 0
- I-Chemical 0
HT6 I-Chemical 0
receptor O 0
antagonist O 0
. O 0

In O 0
addition O 0
, O 0
the O 0
disrupted O 0
prepulse O 0
inhibition O 0
induced O 0
by O 0
d B-Chemical 0
- I-Chemical 0
amphetamine I-Chemical 0
or O 0
phencyclidine B-Chemical 0
was O 0
restored O 0
by O 0
5 B-Chemical 0
- I-Chemical 0
HT6 I-Chemical 0
receptor O 0
antagonist O 0
in O 0
an O 0
animal O 0
study O 0
using O 0
rats O 0
. O 0

These O 0
animal O 0
models O 0
were O 0
considered O 0
to O 0
reflect O 0
the O 0
positive O 0
symptoms O 0
of O 0
schizophrenia B-Disease 0
, O 0
and O 0
the O 0
above O 0
evidence O 0
suggests O 0
that O 0
altered O 0
5 B-Chemical 0
- I-Chemical 0
HT6 I-Chemical 0
receptors O 0
are O 0
involved O 0
in O 0
the O 0
pathophysiology O 0
of O 0
psychotic B-Disease 0
disorders I-Disease 0
. O 0

The O 0
symptoms O 0
of O 0
methamphetamine B-Chemical 0
( O 0
METH B-Chemical 0
) O 0
- O 0
induced O 0
psychosis B-Disease 0
are O 0
similar O 0
to O 0
those O 0
of O 0
paranoid B-Disease 0
type I-Disease 0
schizophrenia I-Disease 0
. O 0

Therefore O 0
, O 0
we O 0
conducted O 0
an O 0
analysis O 0
of O 0
the O 0
association O 0
of O 0
the O 0
5 B-Chemical 0
- I-Chemical 0
HT6 I-Chemical 0
gene O 0
( O 0
HTR6 O 0
) O 0
with O 0
METH B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
. O 0

METHOD O 0
: O 0
Using O 0
five O 0
tagging O 0
SNPs O 0
( O 0
rs6693503 O 0
, O 0
rs1805054 O 0
, O 0
rs4912138 O 0
, O 0
rs3790757 O 0
and O 0
rs9659997 O 0
) O 0
, O 0
we O 0
conducted O 0
a O 0
genetic O 0
association O 0
analysis O 0
of O 0
case O 0
- O 0
control O 0
samples O 0
( O 0
197 O 0
METH B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
patients O 0
and O 0
337 O 0
controls O 0
) O 0
in O 0
the O 0
Japanese O 0
population O 0
. O 0

The O 0
age O 0
and O 0
sex O 0
of O 0
the O 0
control O 0
subjects O 0
did O 0
not O 0
differ O 0
from O 0
those O 0
of O 0
the O 0
methamphetamine B-Chemical 0
dependence O 0
patients O 0
. O 0

RESULTS O 0
: O 0
rs6693503 O 0
was O 0
associated O 0
with O 0
METH B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
patients O 0
in O 0
the O 0
allele O 0
/ O 0
genotype O 0
- O 0
wise O 0
analysis O 0
. O 0

Moreover O 0
, O 0
this O 0
association O 0
remained O 0
significant O 0
after O 0
Bonferroni O 0
correction O 0
. O 0

In O 0
the O 0
haplotype O 0
- O 0
wise O 0
analysis O 0
, O 0
we O 0
detected O 0
an O 0
association O 0
between O 0
two O 0
markers O 0
( O 0
rs6693503 O 0
and O 0
rs1805054 O 0
) O 0
and O 0
three O 0
markers O 0
( O 0
rs6693503 O 0
, O 0
rs1805054 O 0
and O 0
rs4912138 O 0
) O 0
in O 0
HTR6 O 0
and O 0
METH B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
patients O 0
, O 0
respectively O 0
. O 0

CONCLUSION O 0
: O 0
HTR6 O 0
may O 0
play O 0
an O 0
important O 0
role O 0
in O 0
the O 0
pathophysiology O 0
of O 0
METH B-Chemical 0
- O 0
induced O 0
psychosis B-Disease 0
in O 0
the O 0
Japanese O 0
population O 0
. O 0

Neural O 0
correlates O 0
of O 0
S B-Chemical 0
- I-Chemical 0
ketamine I-Chemical 0
induced O 0
psychosis B-Disease 0
during O 0
overt O 0
continuous O 0
verbal O 0
fluency O 0
. O 0

The O 0
glutamatergic 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
has O 0
been O 0
implicated O 0
in O 0
the O 0
pathophysiology O 0
of O 0
schizophrenia B-Disease 0
. O 0

Administered O 0
to O 0
healthy O 0
volunteers O 0
, O 0
a O 0
subanesthetic O 0
dose O 0
of O 0
the O 0
non O 0
- O 0
competitive O 0
NMDA B-Chemical 0
receptor O 0
antagonist O 0
ketamine B-Chemical 0
leads O 0
to O 0
psychopathological O 0
symptoms O 0
similar O 0
to O 0
those O 0
observed O 0
in O 0
schizophrenia B-Disease 0
. O 0

In O 0
patients O 0
with O 0
schizophrenia B-Disease 0
, O 0
ketamine B-Chemical 0
exacerbates O 0
the O 0
core O 0
symptoms O 0
of O 0
illness O 0
, O 0
supporting O 0
the O 0
hypothesis O 0
of O 0
a O 0
glutamatergic B-Disease 0
dysfunction I-Disease 0
. O 0

In O 0
a O 0
counterbalanced O 0
, O 0
placebo O 0
- O 0
controlled O 0
, O 0
double O 0
- O 0
blind O 0
study O 0
design O 0
, O 0
healthy O 0
subjects O 0
were O 0
administered O 0
a O 0
continuous O 0
subanesthetic O 0
S B-Chemical 0
- I-Chemical 0
ketamine I-Chemical 0
infusion O 0
while O 0
differences O 0
in O 0
BOLD O 0
responses O 0
measured O 0
with O 0
fMRI O 0
were O 0
detected O 0
. O 0

During O 0
the O 0
scanning O 0
period O 0
, O 0
subjects O 0
performed O 0
continuous O 0
overt O 0
verbal O 0
fluency O 0
tasks O 0
( O 0
phonological O 0
, O 0
lexical O 0
and O 0
semantic O 0
) O 0
. O 0

Ketamine B-Chemical 0
- O 0
induced O 0
psychopathological O 0
symptoms O 0
were O 0
assessed O 0
with O 0
the O 0
Positive O 0
and O 0
Negative O 0
Syndrome O 0
Scale O 0
( O 0
PANSS O 0
) O 0
. O 0

Ketamine B-Chemical 0
elicited O 0
psychosis B-Disease 0
like O 0
psychopathology O 0
. O 0

Post O 0
- O 0
hoc O 0
t O 0
- O 0
tests O 0
revealed O 0
significant O 0
differences O 0
between O 0
placebo O 0
and O 0
ketamine B-Chemical 0
for O 0
the O 0
amounts O 0
of O 0
words O 0
generated O 0
during O 0
lexical O 0
and O 0
semantic O 0
verbal O 0
fluency O 0
, O 0
while O 0
the O 0
phonological O 0
domain O 0
remained O 0
unaffected O 0
. O 0

Ketamine B-Chemical 0
led O 0
to O 0
enhanced O 0
cortical O 0
activations O 0
in O 0
supramarginal O 0
and O 0
frontal O 0
brain O 0
regions O 0
for O 0
phonological O 0
and O 0
lexical O 0
verbal O 0
fluency O 0
, O 0
but O 0
not O 0
for O 0
semantic O 0
verbal O 0
fluency O 0
. O 0

Ketamine B-Chemical 0
induces O 0
activation O 0
changes O 0
in O 0
healthy O 0
subjects O 0
similar O 0
to O 0
those O 0
observed O 0
in O 0
patients O 0
with O 0
schizophrenia B-Disease 0
, O 0
particularly O 0
in O 0
frontal O 0
and O 0
temporal O 0
brain O 0
regions O 0
. O 0

Our O 0
results O 0
provide O 0
further O 0
support O 0
for O 0
the O 0
hypothesis O 0
of O 0
an O 0
NMDA B-Chemical 0
receptor O 0
dysfunction O 0
in O 0
the O 0
pathophysiology O 0
of O 0
schizophrenia B-Disease 0
. O 0

Long O 0
- O 0
term O 0
prognosis O 0
for O 0
transplant O 0
- O 0
free O 0
survivors O 0
of O 0
paracetamol B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
. O 0

BACKGROUND O 0
: O 0
The O 0
prognosis O 0
for O 0
transplant O 0
- O 0
free O 0
survivors O 0
of O 0
paracetamol B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
remains O 0
unknown O 0
. O 0

AIM O 0
: O 0
To O 0
examine O 0
whether O 0
paracetamol B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
increases O 0
long O 0
- O 0
term O 0
mortality O 0
. O 0

METHODS O 0
: O 0
We O 0
followed O 0
up O 0
all O 0
transplant O 0
- O 0
free O 0
survivors O 0
of O 0
paracetamol B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
liver I-Disease 0
injury I-Disease 0
, O 0
hospitalized O 0
in O 0
a O 0
Danish O 0
national O 0
referral O 0
centre O 0
during O 0
1984 O 0
- O 0
2004 O 0
. O 0

We O 0
compared O 0
age O 0
- O 0
specific O 0
mortality O 0
rates O 0
from O 0
1 O 0
year O 0
post O 0
- O 0
discharge O 0
through O 0
2008 O 0
between O 0
those O 0
in O 0
whom O 0
the O 0
liver B-Disease 0
injury I-Disease 0
led O 0
to O 0
an O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
and O 0
those O 0
in O 0
whom O 0
it O 0
did O 0
not O 0
. O 0

RESULTS O 0
: O 0
We O 0
included O 0
641 O 0
patients O 0
. O 0

On O 0
average O 0
, O 0
age O 0
- O 0
specific O 0
mortality O 0
rates O 0
were O 0
slightly O 0
higher O 0
for O 0
the O 0
101 O 0
patients O 0
whose O 0
paracetamol B-Chemical 0
- O 0
induced O 0
liver B-Disease 0
injury I-Disease 0
had O 0
caused O 0
an O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
( O 0
adjusted O 0
mortality O 0
rate O 0
ratio O 0
= O 0
1 O 0
. O 0
70 O 0
, O 0
95 O 0
% O 0
CI O 0
1 O 0
. O 0
02 O 0
- O 0
2 O 0
. O 0
85 O 0
) O 0
, O 0
but O 0
the O 0
association O 0
was O 0
age O 0
- O 0
dependent O 0
, O 0
and O 0
no O 0
survivors O 0
of O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
died O 0
of O 0
liver B-Disease 0
disease I-Disease 0
, O 0
whereas O 0
suicides O 0
were O 0
frequent O 0
in O 0
both O 0
groups O 0
. O 0

These O 0
observations O 0
speak O 0
against O 0
long O 0
- O 0
term O 0
effects O 0
of O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
. O 0

More O 0
likely O 0
, O 0
the O 0
elevated O 0
mortality O 0
rate O 0
ratio O 0
resulted O 0
from O 0
incomplete O 0
adjustment O 0
for O 0
the O 0
greater O 0
prevalence O 0
of O 0
substance B-Disease 0
abuse I-Disease 0
among O 0
survivors O 0
of O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
Paracetamol B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
did O 0
not O 0
affect O 0
long O 0
- O 0
term O 0
mortality O 0
. O 0

Clinical O 0
follow O 0
- O 0
up O 0
may O 0
be O 0
justified O 0
by O 0
the O 0
cause O 0
of O 0
the O 0
liver B-Disease 0
failure I-Disease 0
, O 0
but O 0
not O 0
by O 0
the O 0
liver B-Disease 0
failure I-Disease 0
itself O 0
. O 0

In O 0
vivo O 0
characterization O 0
of O 0
a O 0
dual O 0
adenosine B-Chemical 0
A2A I-Chemical 0
/ I-Chemical 0
A1 I-Chemical 0
receptor I-Chemical 0
antagonist I-Chemical 0
in O 0
animal O 0
models O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

The O 0
in O 0
vivo O 0
characterization O 0
of O 0
a O 0
dual O 0
adenosine B-Chemical 0
A I-Chemical 0
( I-Chemical 0
2A I-Chemical 0
) I-Chemical 0
/ I-Chemical 0
A I-Chemical 0
( I-Chemical 0
1 I-Chemical 0
) I-Chemical 0
receptor I-Chemical 0
antagonist I-Chemical 0
in O 0
several O 0
animal O 0
models O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
is O 0
described O 0
. O 0

Discovery O 0
and O 0
scale O 0
- O 0
up O 0
syntheses O 0
of O 0
compound O 0
1 O 0
are O 0
described O 0
in O 0
detail O 0
, O 0
highlighting O 0
optimization O 0
steps O 0
that O 0
increased O 0
the O 0
overall O 0
yield O 0
of O 0
1 O 0
from O 0
10 O 0
. O 0
0 O 0
% O 0
to O 0
30 O 0
. O 0
5 O 0
% O 0
. O 0

Compound O 0
1 O 0
is O 0
a O 0
potent O 0
A O 0
( O 0
2A O 0
) O 0
/ O 0
A O 0
( O 0
1 O 0
) O 0
receptor O 0
antagonist O 0
in O 0
vitro O 0
( O 0
A O 0
( O 0
2A O 0
) O 0
K O 0
( O 0
i O 0
) O 0
= O 0
4 O 0
. O 0
1 O 0
nM O 0
; O 0
A O 0
( O 0
1 O 0
) O 0
K O 0
( O 0
i O 0
) O 0
= O 0
17 O 0
. O 0
0 O 0
nM O 0
) O 0
that O 0
has O 0
excellent O 0
activity O 0
, O 0
after O 0
oral O 0
administration O 0
, O 0
across O 0
a O 0
number O 0
of O 0
animal O 0
models O 0
of O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
including O 0
mouse O 0
and O 0
rat O 0
models O 0
of O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
, O 0
mouse O 0
model O 0
of O 0
reserpine B-Chemical 0
- O 0
induced O 0
akinesia B-Disease 0
, O 0
rat O 0
6 B-Chemical 0
- I-Chemical 0
hydroxydopamine I-Chemical 0
( O 0
6 B-Chemical 0
- I-Chemical 0
OHDA I-Chemical 0
) O 0
lesion O 0
model O 0
of O 0
drug O 0
- O 0
induced O 0
rotation O 0
, O 0
and O 0
MPTP B-Chemical 0
- O 0
treated O 0
non O 0
- O 0
human O 0
primate O 0
model O 0
. O 0

Effects O 0
of O 0
the O 0
hippocampal O 0
deep O 0
brain O 0
stimulation O 0
on O 0
cortical O 0
epileptic B-Disease 0
discharges O 0
in O 0
penicillin B-Chemical 0
- O 0
induced O 0
epilepsy B-Disease 0
model O 0
in O 0
rats O 0
. O 0

AIM O 0
: O 0
Experimental O 0
and O 0
clinical O 0
studies O 0
have O 0
revealed O 0
that O 0
hippocampal O 0
DBS O 0
can O 0
control O 0
epileptic B-Disease 0
activity O 0
, O 0
but O 0
the O 0
mechanism O 0
of O 0
action O 0
is O 0
obscure O 0
and O 0
optimal O 0
stimulation O 0
parameters O 0
are O 0
not O 0
clearly O 0
defined O 0
. O 0

The O 0
aim O 0
was O 0
to O 0
evaluate O 0
the O 0
effects O 0
of O 0
high O 0
frequency O 0
hippocampal O 0
stimulation O 0
on O 0
cortical O 0
epileptic B-Disease 0
activity O 0
in O 0
penicillin B-Chemical 0
- O 0
induced O 0
epilepsy B-Disease 0
model O 0
. O 0

MATERIAL O 0
AND O 0
METHODS O 0
: O 0
Twenty O 0
- O 0
five O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
were O 0
implanted O 0
DBS O 0
electrodes O 0
. O 0

In O 0
group O 0
- O 0
1 O 0
( O 0
n O 0
= O 0
10 O 0
) O 0
hippocampal O 0
DBS O 0
was O 0
off O 0
and O 0
in O 0
the O 0
group O 0
- O 0
2 O 0
( O 0
n O 0
= O 0
10 O 0
) O 0
hippocampal O 0
DBS O 0
was O 0
on O 0
( O 0
185 O 0
Hz O 0
, O 0
0 O 0
. O 0
5V O 0
, O 0
1V O 0
, O 0
2V O 0
, O 0
and O 0
5V O 0
for O 0
60 O 0
sec O 0
) O 0
following O 0
penicillin B-Chemical 0
G I-Chemical 0
injection O 0
intracortically O 0
. O 0

In O 0
the O 0
control O 0
group O 0
hippocampal O 0
DBS O 0
was O 0
on O 0
following O 0
8 O 0
l O 0
saline O 0
injection O 0
intracortically O 0
. O 0

EEG O 0
recordings O 0
were O 0
obtained O 0
before O 0
and O 0
15 O 0
minutes O 0
following O 0
penicillin B-Chemical 0
- I-Chemical 0
G I-Chemical 0
injection O 0
, O 0
and O 0
at O 0
10th O 0
minutes O 0
following O 0
each O 0
stimulus O 0
for O 0
analysis O 0
in O 0
terms O 0
of O 0
frequency O 0
, O 0
amplitude O 0
, O 0
and O 0
power O 0
spectrum O 0
. O 0

RESULTS O 0
: O 0
High O 0
frequency O 0
hippocampal O 0
DBS O 0
suppressed O 0
the O 0
acute O 0
penicillin B-Chemical 0
- O 0
induced O 0
cortical O 0
epileptic B-Disease 0
activity O 0
independent O 0
from O 0
stimulus O 0
intensity O 0
. O 0

In O 0
the O 0
control O 0
group O 0
, O 0
hippocampal O 0
stimulation O 0
alone O 0
lead O 0
only O 0
to O 0
diffuse O 0
slowing O 0
of O 0
cerebral O 0
bioelectrical O 0
activity O 0
at O 0
5V O 0
stimulation O 0
. O 0

CONCLUSION O 0
: O 0
Our O 0
results O 0
revealed O 0
that O 0
continuous O 0
high O 0
frequency O 0
stimulation O 0
of O 0
the O 0
hippocampus O 0
suppressed O 0
acute O 0
cortical O 0
epileptic B-Disease 0
activity O 0
effectively O 0
without O 0
causing O 0
secondary O 0
epileptic B-Disease 0
discharges O 0
. O 0

These O 0
results O 0
are O 0
important O 0
in O 0
terms O 0
of O 0
defining O 0
the O 0
optimal O 0
parameters O 0
of O 0
hippocampal O 0
DBS O 0
in O 0
patients O 0
with O 0
epilepsy B-Disease 0
. O 0

CCNU B-Chemical 0
( O 0
lomustine B-Chemical 0
) O 0
toxicity B-Disease 0
in O 0
dogs O 0
: O 0
a O 0
retrospective O 0
study O 0
( O 0
2002 O 0
- O 0
07 O 0
) O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
describe O 0
the O 0
incidence O 0
of O 0
haematological B-Disease 0
, I-Disease 0
renal I-Disease 0
, I-Disease 0
hepatic I-Disease 0
and I-Disease 0
gastrointestinal I-Disease 0
toxicities I-Disease 0
in O 0
tumour O 0
- O 0
bearing O 0
dogs O 0
receiving O 0
1 B-Chemical 0
- I-Chemical 0
( I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
chloroethyl I-Chemical 0
) I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
cyclohexyl I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
nitrosourea I-Chemical 0
( O 0
CCNU B-Chemical 0
) O 0
. O 0

DESIGN O 0
: O 0
The O 0
medical O 0
records O 0
of O 0
206 O 0
dogs O 0
that O 0
were O 0
treated O 0
with O 0
CCNU B-Chemical 0
at O 0
the O 0
Melbourne O 0
Veterinary O 0
Specialist O 0
Centre O 0
between O 0
February O 0
2002 O 0
and O 0
December O 0
2007 O 0
were O 0
retrospectively O 0
evaluated O 0
. O 0

RESULTS O 0
: O 0
Of O 0
the O 0
206 O 0
dogs O 0
treated O 0
with O 0
CCNU B-Chemical 0
, O 0
185 O 0
met O 0
the O 0
inclusion O 0
criteria O 0
for O 0
at O 0
least O 0
one O 0
class O 0
of O 0
toxicity B-Disease 0
. O 0

CCNU B-Chemical 0
was O 0
used O 0
most O 0
commonly O 0
in O 0
the O 0
treatment O 0
of O 0
lymphoma B-Disease 0
, O 0
mast B-Disease 0
cell I-Disease 0
tumour I-Disease 0
, O 0
brain B-Disease 0
tumour I-Disease 0
, O 0
histiocytic B-Disease 0
tumours I-Disease 0
and O 0
epitheliotropic B-Disease 0
lymphoma I-Disease 0
. O 0

Throughout O 0
treatment O 0
, O 0
56 O 0
. O 0
9 O 0
% O 0
of O 0
dogs O 0
experienced O 0
neutropenia B-Disease 0
, O 0
34 O 0
. O 0
2 O 0
% O 0
experienced O 0
anaemia B-Disease 0
and O 0
14 O 0
. O 0
2 O 0
% O 0
experienced O 0
thrombocytopenia B-Disease 0
. O 0

Gastrointestinal B-Disease 0
toxicosis I-Disease 0
was O 0
detected O 0
in O 0
37 O 0
. O 0
8 O 0
% O 0
of O 0
dogs O 0
, O 0
the O 0
most O 0
common O 0
sign O 0
of O 0
which O 0
was O 0
vomiting B-Disease 0
( O 0
24 O 0
. O 0
3 O 0
% O 0
) O 0
. O 0

Potential O 0
renal O 0
toxicity B-Disease 0
and O 0
elevated O 0
alanine B-Chemical 0
transaminase O 0
( O 0
ALT O 0
) O 0
concentration O 0
were O 0
reported O 0
in O 0
12 O 0
. O 0
2 O 0
% O 0
and O 0
48 O 0
. O 0
8 O 0
% O 0
of O 0
dogs O 0
, O 0
respectively O 0
. O 0

The O 0
incidence O 0
of O 0
hepatic B-Disease 0
failure I-Disease 0
was O 0
1 O 0
. O 0
2 O 0
% O 0
. O 0

CONCLUSIONS O 0
: O 0
CCNU B-Chemical 0
- O 0
associated O 0
toxicity B-Disease 0
in O 0
dogs O 0
is O 0
common O 0
, O 0
but O 0
is O 0
usually O 0
not O 0
life O 0
threatening O 0
. O 0

Central O 0
vein B-Disease 0
thrombosis I-Disease 0
and O 0
topical O 0
dipivalyl B-Chemical 0
epinephrine I-Chemical 0
. O 0

A O 0
report O 0
is O 0
given O 0
on O 0
an O 0
83 O 0
- O 0
year O 0
- O 0
old O 0
female O 0
who O 0
acquired O 0
central O 0
vein B-Disease 0
thrombosis I-Disease 0
in O 0
her O 0
seeing O 0
eye O 0
one O 0
day O 0
after O 0
having O 0
started O 0
topical O 0
medication O 0
with O 0
dipivalyl B-Chemical 0
epinephrine I-Chemical 0
for O 0
advanced O 0
glaucoma B-Disease 0
discovered O 0
in O 0
the O 0
other O 0
eye O 0
. O 0

From O 0
present O 0
knowledge O 0
about O 0
the O 0
effects O 0
of O 0
adrenergic O 0
eye O 0
drops O 0
on O 0
ocular O 0
blood O 0
circulation O 0
, O 0
it O 0
is O 0
difficult O 0
to O 0
suggest O 0
an O 0
association O 0
between O 0
the O 0
two O 0
events O 0
, O 0
which O 0
may O 0
be O 0
coincidental O 0
only O 0
. O 0

Benzylacyclouridine B-Chemical 0
reverses O 0
azidothymidine B-Chemical 0
- O 0
induced O 0
marrow B-Disease 0
suppression I-Disease 0
without O 0
impairment O 0
of O 0
anti O 0
- O 0
human O 0
immunodeficiency B-Disease 0
virus O 0
activity O 0
. O 0

Increased O 0
extracellular O 0
concentrations O 0
of O 0
uridine B-Chemical 0
( O 0
Urd B-Chemical 0
) O 0
have O 0
been O 0
reported O 0
to O 0
reduce O 0
, O 0
in O 0
vitro O 0
, O 0
azidothymidine B-Chemical 0
( O 0
AZT B-Chemical 0
) O 0
- O 0
induced O 0
inhibition O 0
of O 0
human O 0
granulocyte O 0
- O 0
macrophage O 0
progenitor O 0
cells O 0
without O 0
impairment O 0
of O 0
its O 0
antihuman O 0
immunodeficiency B-Disease 0
virus O 0
( O 0
HIV O 0
) O 0
activity O 0
. O 0

Because O 0
of O 0
the O 0
clinical O 0
toxicities B-Disease 0
associated O 0
with O 0
chronic O 0
Urd B-Chemical 0
administration O 0
, O 0
the O 0
ability O 0
of O 0
benzylacyclouridine B-Chemical 0
( O 0
BAU B-Chemical 0
) O 0
to O 0
effect O 0
, O 0
in O 0
vivo O 0
, O 0
AZT B-Chemical 0
- O 0
induced O 0
anemia B-Disease 0
and O 0
leukopenia B-Disease 0
was O 0
assessed O 0
. O 0

This O 0
agent O 0
inhibits O 0
Urd B-Chemical 0
catabolism O 0
and O 0
, O 0
in O 0
vivo O 0
, O 0
increases O 0
the O 0
plasma O 0
concentration O 0
of O 0
Urd B-Chemical 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
manner O 0
, O 0
without O 0
Urd B-Chemical 0
- O 0
related O 0
toxicity B-Disease 0
. O 0

In O 0
mice O 0
rendered O 0
anemic B-Disease 0
and O 0
leukopenic B-Disease 0
by O 0
the O 0
administration O 0
of O 0
AZT B-Chemical 0
for O 0
28 O 0
days O 0
in O 0
drinking O 0
water O 0
( O 0
1 O 0
. O 0
5 O 0
mg O 0
/ O 0
mL O 0
) O 0
, O 0
the O 0
continued O 0
administration O 0
of O 0
AZT B-Chemical 0
plus O 0
daily O 0
BAU B-Chemical 0
( O 0
300 O 0
mg O 0
/ O 0
kg O 0
, O 0
orally O 0
) O 0
partially O 0
reversed O 0
AZT B-Chemical 0
- O 0
induced O 0
anemia B-Disease 0
and O 0
leukopenia B-Disease 0
( O 0
P O 0
less O 0
than O 0
. O 0
05 O 0
) O 0
, O 0
increased O 0
peripheral O 0
reticulocytes O 0
( O 0
to O 0
4 O 0
. O 0
9 O 0
% O 0
, O 0
P O 0
less O 0
than O 0
. O 0
01 O 0
) O 0
, O 0
increased O 0
cellularity O 0
in O 0
the O 0
marrow O 0
, O 0
and O 0
improved O 0
megaloblastosis B-Disease 0
. O 0

When O 0
coadministered O 0
with O 0
AZT B-Chemical 0
from O 0
the O 0
onset O 0
of O 0
drug O 0
administration O 0
, O 0
BAU B-Chemical 0
reduced O 0
AZT B-Chemical 0
- O 0
induced O 0
marrow B-Disease 0
toxicity I-Disease 0
. O 0

In O 0
vitro O 0
, O 0
at O 0
a O 0
concentration O 0
of O 0
100 O 0
mumol O 0
/ O 0
L O 0
, O 0
BAU B-Chemical 0
possesses O 0
minimal O 0
anti O 0
- O 0
HIV O 0
activity O 0
and O 0
has O 0
no O 0
effect O 0
on O 0
the O 0
ability O 0
of O 0
AZT B-Chemical 0
to O 0
reverse O 0
the O 0
HIV O 0
- O 0
induced O 0
cytopathic O 0
effect O 0
in O 0
MT4 O 0
cells O 0
. O 0

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

Lethal O 0
anuria B-Disease 0
complicating O 0
high O 0
dose O 0
ifosfamide B-Chemical 0
chemotherapy O 0
in O 0
a O 0
breast B-Disease 0
cancer I-Disease 0
patient O 0
with O 0
an O 0
impaired B-Disease 0
renal I-Disease 0
function I-Disease 0
. O 0

A O 0
sixty O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
advanced O 0
breast B-Disease 0
cancer I-Disease 0
, O 0
previously O 0
treated O 0
with O 0
cisplatin B-Chemical 0
, O 0
developed O 0
an O 0
irreversible O 0
lethal O 0
renal B-Disease 0
failure I-Disease 0
with O 0
anuria B-Disease 0
, O 0
the O 0
day O 0
after O 0
5 O 0
g O 0
/ O 0
m2 O 0
bolus O 0
ifosfamide B-Chemical 0
. O 0

Postrenal B-Disease 0
failure I-Disease 0
was O 0
excluded O 0
by O 0
echography O 0
. O 0

A O 0
prerenal O 0
component O 0
could O 0
have O 0
contributed O 0
to O 0
renal B-Disease 0
failure I-Disease 0
because O 0
of O 0
a O 0
transient O 0
hypotension B-Disease 0
, O 0
due O 0
to O 0
an O 0
increasing O 0
ascitis O 0
, O 0
occurring O 0
just O 0
before O 0
anuria B-Disease 0
. O 0

However O 0
, O 0
correction O 0
of O 0
the O 0
hemodynamic O 0
parameters O 0
did O 0
not O 0
improve O 0
renal O 0
function O 0
. O 0

Ifosfamide B-Chemical 0
is O 0
a O 0
known O 0
nephrotoxic B-Disease 0
drug O 0
with O 0
demonstrated O 0
tubulopathies B-Disease 0
. O 0

We O 0
strongly O 0
suspect O 0
that O 0
this O 0
lethal O 0
anuria B-Disease 0
was O 0
mainly O 0
due O 0
to O 0
ifosfamide B-Chemical 0
, O 0
occurring O 0
in O 0
a O 0
patient O 0
having O 0
received O 0
previous O 0
cisplatin B-Chemical 0
chemotherapy O 0
and O 0
with O 0
poor O 0
kidney O 0
perfusion O 0
due O 0
to O 0
transient O 0
hypotension B-Disease 0
. O 0

We O 0
recommend O 0
careful O 0
use O 0
of O 0
ifosfamide B-Chemical 0
in O 0
patients O 0
pretreated O 0
with O 0
nephrotoxic B-Disease 0
chemotherapy O 0
and O 0
inadequate O 0
renal O 0
perfusion O 0
. O 0

Nociceptive O 0
effects O 0
induced O 0
by O 0
intrathecal O 0
administration O 0
of O 0
prostaglandin B-Chemical 0
D2 I-Chemical 0
, I-Chemical 0
E2 I-Chemical 0
, I-Chemical 0
or I-Chemical 0
F2 I-Chemical 0
alpha I-Chemical 0
to O 0
conscious O 0
mice O 0
. O 0

The O 0
effects O 0
of O 0
intrathecal O 0
administration O 0
of O 0
prostaglandins B-Chemical 0
on O 0
pain B-Disease 0
responses O 0
in O 0
conscious O 0
mice O 0
were O 0
evaluated O 0
by O 0
using O 0
hot O 0
plate O 0
and O 0
acetic B-Chemical 0
acid I-Chemical 0
writhing O 0
tests O 0
. O 0

Prostaglandin B-Chemical 0
D2 I-Chemical 0
( O 0
0 O 0
. O 0
5 O 0
- O 0
3 O 0
ng O 0
/ O 0
mouse O 0
) O 0
had O 0
a O 0
hyperalgesic B-Disease 0
action O 0
on O 0
the O 0
response O 0
to O 0
a O 0
hot O 0
plate O 0
during O 0
a O 0
3 O 0
- O 0
60 O 0
min O 0
period O 0
after O 0
injection O 0
. O 0

Prostaglandin B-Chemical 0
E2 I-Chemical 0
showed O 0
a O 0
hyperalgesic B-Disease 0
effect O 0
at O 0
doses O 0
of O 0
1 O 0
pg B-Chemical 0
to O 0
10 O 0
ng O 0
/ O 0
mouse O 0
, O 0
but O 0
the O 0
effect O 0
lasted O 0
shorter O 0
( O 0
3 O 0
- O 0
30 O 0
min O 0
) O 0
than O 0
that O 0
of O 0
prostaglandin B-Chemical 0
D2 I-Chemical 0
. O 0

Similar O 0
results O 0
were O 0
obtained O 0
by O 0
acetic B-Chemical 0
acid I-Chemical 0
writhing O 0
tests O 0
. O 0

The O 0
hyperalgesic B-Disease 0
effect O 0
of O 0
prostaglandin B-Chemical 0
D2 I-Chemical 0
was O 0
blocked O 0
by O 0
simultaneous O 0
injection O 0
of O 0
a O 0
substance O 0
P O 0
antagonist O 0
( O 0
greater O 0
than O 0
or O 0
equal O 0
to O 0
100 O 0
ng O 0
) O 0
but O 0
not O 0
by O 0
AH6809 B-Chemical 0
, O 0
a O 0
prostanoid O 0
EP1 O 0
- O 0
receptor O 0
antagonist O 0
. O 0

Conversely O 0
, O 0
prostaglandin B-Chemical 0
E2 I-Chemical 0
- O 0
induced O 0
hyperalgesia B-Disease 0
was O 0
blocked O 0
by O 0
AH6809 B-Chemical 0
( O 0
greater O 0
than O 0
or O 0
equal O 0
to O 0
500 O 0
ng O 0
) O 0
but O 0
not O 0
by O 0
the O 0
substance O 0
P O 0
antagonist O 0
. O 0

Prostaglandin B-Chemical 0
F2 I-Chemical 0
alpha I-Chemical 0
had O 0
little O 0
effect O 0
on O 0
pain B-Disease 0
responses O 0
. O 0

These O 0
results O 0
demonstrate O 0
that O 0
both O 0
prostaglandin B-Chemical 0
D2 I-Chemical 0
and O 0
prostaglandin B-Chemical 0
E2 I-Chemical 0
exert O 0
hyperalgesia B-Disease 0
in O 0
the O 0
spinal O 0
cord O 0
, O 0
but O 0
in O 0
different O 0
ways O 0
. O 0

D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
localized B-Disease 0
scleroderma I-Disease 0
. O 0

Localized B-Disease 0
scleroderma I-Disease 0
has O 0
no O 0
recognized O 0
internal O 0
organ O 0
involvement O 0
but O 0
may O 0
be O 0
disfiguring O 0
and O 0
disabling O 0
when O 0
the O 0
cutaneous O 0
lesions O 0
are O 0
extensive O 0
or O 0
affect O 0
children O 0
. O 0

There O 0
is O 0
no O 0
accepted O 0
or O 0
proven O 0
treatment O 0
for O 0
localized B-Disease 0
scleroderma I-Disease 0
. O 0

Case O 0
reports O 0
of O 0
11 O 0
patients O 0
with O 0
severe O 0
, O 0
extensive O 0
localized B-Disease 0
scleroderma I-Disease 0
who O 0
were O 0
treated O 0
with O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
are O 0
summarized O 0
in O 0
this O 0
article O 0
. O 0

This O 0
drug O 0
was O 0
judged O 0
to O 0
have O 0
a O 0
favorable O 0
effect O 0
on O 0
the O 0
disease O 0
course O 0
in O 0
7 O 0
( O 0
64 O 0
% O 0
) O 0
of O 0
11 O 0
patients O 0
. O 0

Improvement O 0
began O 0
within O 0
3 O 0
to O 0
6 O 0
months O 0
and O 0
consisted O 0
of O 0
cessation O 0
of O 0
active O 0
cutaneous O 0
lesions O 0
in O 0
all O 0
7 O 0
patients O 0
, O 0
skin O 0
softening O 0
in O 0
5 O 0
, O 0
and O 0
more O 0
normal O 0
growth O 0
of O 0
the O 0
affected O 0
limb O 0
in O 0
2 O 0
of O 0
3 O 0
children O 0
. O 0

Joint O 0
stiffness O 0
and O 0
contractures B-Disease 0
also O 0
improved O 0
. O 0

The O 0
dose O 0
of O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
associated O 0
with O 0
a O 0
favorable O 0
response O 0
was O 0
as O 0
low O 0
as O 0
2 O 0
to O 0
5 O 0
mg O 0
/ O 0
kg O 0
per O 0
day O 0
given O 0
over O 0
a O 0
period O 0
ranging O 0
from O 0
15 O 0
to O 0
53 O 0
months O 0
. O 0

D B-Chemical 0
- I-Chemical 0
Penicillamine I-Chemical 0
caused O 0
nephrotic B-Disease 0
syndrome I-Disease 0
in O 0
1 O 0
patient O 0
and O 0
milder O 0
reversible O 0
proteinuria B-Disease 0
in O 0
3 O 0
other O 0
patients O 0
; O 0
none O 0
developed O 0
renal B-Disease 0
insufficiency I-Disease 0
. O 0

These O 0
data O 0
suggest O 0
that O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
may O 0
be O 0
effective O 0
in O 0
severe O 0
cases O 0
of O 0
localized B-Disease 0
scleroderma I-Disease 0
. O 0

Cerebral B-Disease 0
sinus I-Disease 0
thrombosis I-Disease 0
as O 0
a O 0
potential O 0
hazard O 0
of O 0
antifibrinolytic O 0
treatment O 0
in O 0
menorrhagia B-Disease 0
. O 0

We O 0
describe O 0
a O 0
42 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
who O 0
developed O 0
superior O 0
sagittal B-Disease 0
and I-Disease 0
left I-Disease 0
transverse I-Disease 0
sinus I-Disease 0
thrombosis I-Disease 0
associated O 0
with O 0
prolonged O 0
epsilon B-Chemical 0
- I-Chemical 0
aminocaproic I-Chemical 0
acid I-Chemical 0
therapy O 0
for O 0
menorrhagia B-Disease 0
. O 0

This O 0
antifibrinolytic O 0
agent O 0
has O 0
been O 0
used O 0
in O 0
women O 0
with O 0
menorrhagia B-Disease 0
to O 0
promote O 0
clotting O 0
and O 0
reduce O 0
blood B-Disease 0
loss I-Disease 0
. O 0

Although O 0
increased O 0
risk O 0
of O 0
thromboembolic B-Disease 0
disease I-Disease 0
has O 0
been O 0
reported O 0
during O 0
treatment O 0
with O 0
epsilon B-Chemical 0
- I-Chemical 0
aminocaproic I-Chemical 0
acid I-Chemical 0
, O 0
cerebral B-Disease 0
sinus I-Disease 0
thrombosis I-Disease 0
has O 0
not O 0
been O 0
previously O 0
described O 0
. O 0

Careful O 0
use O 0
of O 0
epsilon B-Chemical 0
- I-Chemical 0
aminocaproic I-Chemical 0
acid I-Chemical 0
therapy O 0
is O 0
recommended O 0
. O 0

Seizure B-Disease 0
activity O 0
with O 0
imipenem B-Chemical 0
therapy O 0
: O 0
incidence O 0
and O 0
risk O 0
factors O 0
. O 0

Two O 0
elderly O 0
patients O 0
with O 0
a O 0
history O 0
of O 0
either O 0
cerebral B-Disease 0
vascular I-Disease 0
accident I-Disease 0
( O 0
CVA B-Disease 0
) O 0
or O 0
head B-Disease 0
trauma I-Disease 0
and O 0
no O 0
evidence O 0
of O 0
renal B-Disease 0
disease I-Disease 0
developed O 0
seizures B-Disease 0
while O 0
receiving O 0
maximum O 0
doses O 0
of O 0
imipenem B-Chemical 0
/ I-Chemical 0
cilastatin I-Chemical 0
. O 0

Neither O 0
patient O 0
had O 0
reported O 0
previous O 0
seizures B-Disease 0
or O 0
seizure B-Disease 0
- O 0
like O 0
activity O 0
nor O 0
was O 0
receiving O 0
anticonvulsant O 0
agents O 0
. O 0

All O 0
seizures B-Disease 0
were O 0
controlled O 0
with O 0
therapeutic O 0
doses O 0
of O 0
phenytoin B-Chemical 0
. O 0

Both O 0
patients O 0
had O 0
received O 0
maximum O 0
doses O 0
of O 0
other O 0
beta B-Chemical 0
- I-Chemical 0
lactam I-Chemical 0
antibiotics O 0
without O 0
evidence O 0
of O 0
seizure B-Disease 0
activity O 0
. O 0

Midline O 0
B3 O 0
serotonin B-Chemical 0
nerves O 0
in O 0
rat O 0
medulla O 0
are O 0
involved O 0
in O 0
hypotensive B-Disease 0
effect O 0
of O 0
methyldopa B-Chemical 0
. O 0

Previous O 0
experiments O 0
in O 0
this O 0
laboratory O 0
have O 0
shown O 0
that O 0
microinjection O 0
of O 0
methyldopa B-Chemical 0
onto O 0
the O 0
ventrolateral O 0
cells O 0
of O 0
the O 0
B3 O 0
serotonin B-Chemical 0
neurons O 0
in O 0
the O 0
medulla O 0
elicits O 0
a O 0
hypotensive B-Disease 0
response O 0
mediated O 0
by O 0
a O 0
projection O 0
descending O 0
into O 0
the O 0
spinal O 0
cord O 0
. O 0

The O 0
present O 0
experiments O 0
were O 0
designed O 0
to O 0
investigate O 0
the O 0
role O 0
of O 0
the O 0
midline O 0
cells O 0
of O 0
the O 0
B3 O 0
serotonin B-Chemical 0
neurons O 0
in O 0
the O 0
medulla O 0
, O 0
coinciding O 0
with O 0
the O 0
raphe O 0
magnus O 0
. O 0

In O 0
spontaneously O 0
hypertensive B-Disease 0
, O 0
stroke B-Disease 0
- O 0
prone O 0
rats O 0
, O 0
microinjection O 0
of O 0
methyldopa B-Chemical 0
into O 0
the O 0
area O 0
of O 0
the O 0
midline O 0
B3 O 0
serotonin B-Chemical 0
cell O 0
group O 0
in O 0
the O 0
ventral O 0
medulla O 0
caused O 0
a O 0
potent O 0
hypotension B-Disease 0
of O 0
30 O 0
- O 0
40 O 0
mm O 0
Hg O 0
, O 0
which O 0
was O 0
maximal O 0
2 O 0
- O 0
3 O 0
h O 0
after O 0
administration O 0
and O 0
was O 0
abolished O 0
by O 0
the O 0
serotonin B-Chemical 0
neurotoxin O 0
5 B-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
dihydroxytryptamine I-Chemical 0
( O 0
5 B-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
DHT I-Chemical 0
) O 0
injected O 0
intracerebroventricularly O 0
. O 0

However O 0
, O 0
intraspinal O 0
injection O 0
of O 0
5 B-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
DHT I-Chemical 0
to O 0
produce O 0
a O 0
more O 0
selective O 0
lesion O 0
of O 0
only O 0
descending O 0
serotonin B-Chemical 0
projections O 0
in O 0
the O 0
spinal O 0
cord O 0
did O 0
not O 0
affect O 0
this O 0
hypotension B-Disease 0
. O 0

Further O 0
, O 0
5 B-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
DHT I-Chemical 0
lesion O 0
of O 0
serotonin B-Chemical 0
nerves O 0
travelling O 0
in O 0
the O 0
median O 0
forebrain O 0
bundle O 0
, O 0
one O 0
of O 0
the O 0
main O 0
ascending O 0
pathways O 0
from O 0
the O 0
B3 O 0
serotonin B-Chemical 0
cells O 0
, O 0
did O 0
not O 0
affect O 0
the O 0
fall O 0
in O 0
blood O 0
pressure O 0
associated O 0
with O 0
a O 0
midline O 0
B3 O 0
serotonin B-Chemical 0
methyldopa B-Chemical 0
injection O 0
. O 0

It O 0
is O 0
concluded O 0
therefore O 0
that O 0
, O 0
unlike O 0
the O 0
ventrolateral O 0
B3 O 0
cells O 0
which O 0
mediate O 0
a O 0
methyldopa B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
via O 0
descending O 0
projections O 0
, O 0
the O 0
midline O 0
serotonin B-Chemical 0
B3 O 0
cells O 0
in O 0
the O 0
medulla O 0
contribute O 0
to O 0
the O 0
hypotensive B-Disease 0
action O 0
of O 0
methyldopa B-Chemical 0
, O 0
either O 0
by O 0
way O 0
of O 0
an O 0
ascending O 0
projection O 0
which O 0
does O 0
not O 0
pass O 0
through O 0
the O 0
median O 0
forebrain O 0
bundle O 0
, O 0
or O 0
through O 0
a O 0
projection O 0
restricted O 0
to O 0
the O 0
caudal O 0
brainstem O 0
. O 0

Antiarrhythmic O 0
plasma O 0
concentrations O 0
of O 0
cibenzoline B-Chemical 0
on O 0
canine O 0
ventricular B-Disease 0
arrhythmias I-Disease 0
. O 0

Using O 0
two O 0
- O 0
stage O 0
coronary O 0
ligation O 0
- O 0
, O 0
digitalis B-Chemical 0
- O 0
, O 0
and O 0
adrenaline B-Chemical 0
- O 0
induced O 0
canine O 0
ventricular B-Disease 0
arrhythmias I-Disease 0
, O 0
antiarrhythmic O 0
effects O 0
of O 0
cibenzoline B-Chemical 0
were O 0
examined O 0
and O 0
the O 0
minimum O 0
effective O 0
plasma O 0
concentration O 0
for O 0
each O 0
arrhythmia B-Disease 0
model O 0
was O 0
determined O 0
. O 0

Cibenzoline B-Chemical 0
suppressed O 0
all O 0
the O 0
arrhythmias B-Disease 0
, O 0
and O 0
the O 0
minimum O 0
effective O 0
plasma O 0
concentrations O 0
for O 0
arrhythmias B-Disease 0
induced O 0
by O 0
24 O 0
- O 0
h O 0
coronary O 0
ligation O 0
, O 0
48 O 0
- O 0
h O 0
coronary O 0
ligation O 0
, O 0
digitalis B-Chemical 0
, O 0
and O 0
adrenaline B-Chemical 0
were O 0
1 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
9 O 0
( O 0
by O 0
8 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
) O 0
, O 0
1 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
5 O 0
( O 0
by O 0
8 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
) O 0
, O 0
0 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
( O 0
by O 0
2 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
) O 0
, O 0
and O 0
3 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
3 O 0
( O 0
by 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
micrograms O 0
/ O 0
ml O 0
, O 0
respectively O 0
( O 0
mean O 0
+ O 0
/ O 0
- O 0
SDM O 0
, O 0
n O 0
= O 0
6 O 0
- O 0
7 O 0
) O 0
. O 0

The O 0
concentration O 0
for O 0
adrenaline B-Chemical 0
- O 0
induced O 0
arrhythmia B-Disease 0
was O 0
significantly O 0
higher O 0
than O 0
those O 0
for O 0
the O 0
other O 0
types O 0
of O 0
arrhythmias B-Disease 0
. O 0

This O 0
pharmacological O 0
profile O 0
is O 0
similar O 0
to O 0
those O 0
of O 0
mexiletine B-Chemical 0
and O 0
tocainide B-Chemical 0
, O 0
and O 0
all O 0
three O 0
drugs O 0
have O 0
central O 0
nervous O 0
system O 0
( O 0
CNS O 0
) O 0
stimulant O 0
action O 0
. O 0

Because O 0
cibenzoline B-Chemical 0
had O 0
only O 0
weak O 0
hypotensive B-Disease 0
and O 0
sinus O 0
node O 0
depressive B-Disease 0
effects O 0
and O 0
was O 0
found O 0
to O 0
be O 0
orally O 0
active O 0
when O 0
given O 0
to O 0
coronary O 0
ligation O 0
arrhythmia B-Disease 0
dogs O 0
, O 0
its O 0
clinical O 0
usefulness O 0
is O 0
expected O 0
. O 0

Continuous O 0
ambulatory O 0
ECG O 0
monitoring O 0
during O 0
fluorouracil B-Chemical 0
therapy O 0
: O 0
a O 0
prospective O 0
study O 0
. O 0

Although O 0
there O 0
have O 0
been O 0
anecdotal O 0
reports O 0
of O 0
cardiac B-Disease 0
toxicity I-Disease 0
associated O 0
with O 0
fluorouracil B-Chemical 0
( O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
) O 0
therapy O 0
, O 0
this O 0
phenomenon O 0
has O 0
not O 0
been O 0
studied O 0
in O 0
a O 0
systematic O 0
fashion O 0
. O 0

We O 0
prospectively O 0
performed O 0
continuous O 0
ambulatory O 0
ECG O 0
monitoring O 0
on O 0
25 O 0
patients O 0
undergoing O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
infusion O 0
for O 0
treatment O 0
of O 0
solid O 0
tumors B-Disease 0
in O 0
order O 0
to O 0
assess O 0
the O 0
incidence O 0
of O 0
ischemic B-Disease 0
ST O 0
changes O 0
. O 0

Patients O 0
were O 0
monitored O 0
for O 0
23 O 0
+ O 0
/ O 0
- O 0
4 O 0
hours O 0
before O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
infusion O 0
, O 0
and O 0
98 O 0
+ O 0
/ O 0
- O 0
9 O 0
hours O 0
during O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
infusion O 0
. O 0

Anginal B-Disease 0
episodes O 0
were O 0
rare O 0
: O 0
only O 0
one O 0
patient O 0
had O 0
angina B-Disease 0
( O 0
during O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
infusion O 0
) O 0
. O 0

However O 0
, O 0
asymptomatic O 0
ST O 0
changes O 0
( O 0
greater O 0
than O 0
or O 0
equal O 0
to O 0
1 O 0
mm O 0
ST O 0
deviation O 0
) O 0
were O 0
common O 0
: O 0
six O 0
of O 0
25 O 0
patients O 0
( O 0
24 O 0
% O 0
) O 0
had O 0
ST O 0
changes O 0
before O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
infusion O 0
v O 0
17 O 0
( O 0
68 O 0
% O 0
) O 0
during O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
infusion O 0
( O 0
P O 0
less O 0
than O 0
. O 0
002 O 0
) O 0
. O 0

The O 0
incidence O 0
of O 0
ischemic B-Disease 0
episodes O 0
per O 0
patient O 0
per O 0
hour O 0
was O 0
0 O 0
. O 0
05 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
02 O 0
prior O 0
to O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
infusion O 0
v O 0
0 O 0
. O 0
13 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
03 O 0
during O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
infusion O 0
( O 0
P O 0
less O 0
than O 0
. O 0
001 O 0
) O 0
; O 0
the O 0
duration O 0
of O 0
ECG O 0
changes O 0
was O 0
0 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
3 O 0
minutes O 0
per O 0
patient O 0
per O 0
hour O 0
before O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
v O 0
1 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
5 O 0
minutes O 0
per O 0
patient O 0
per O 0
hour O 0
during O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
( O 0
P O 0
less O 0
than O 0
. O 0
01 O 0
) O 0
. O 0

ECG O 0
changes O 0
were O 0
more O 0
common O 0
among O 0
patients O 0
with O 0
known O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
. O 0

There O 0
were O 0
two O 0
cases O 0
of O 0
sudden B-Disease 0
death I-Disease 0
, O 0
both O 0
of O 0
which O 0
occurred O 0
at O 0
the O 0
end O 0
of O 0
the O 0
chemotherapy O 0
course O 0
. O 0

We O 0
conclude O 0
that O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
infusion O 0
is O 0
associated O 0
with O 0
a O 0
significant O 0
increase O 0
in O 0
silent O 0
ST O 0
segment O 0
deviation O 0
suggestive O 0
of O 0
ischemia B-Disease 0
, O 0
particularly O 0
among O 0
patients O 0
with O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
. O 0

The O 0
mechanism O 0
and O 0
clinical O 0
significance O 0
of O 0
these O 0
ECG O 0
changes O 0
remain O 0
to O 0
be O 0
determined O 0
. O 0

Nature O 0
, O 0
time O 0
course O 0
and O 0
dose O 0
dependence O 0
of O 0
zidovudine B-Chemical 0
- O 0
related O 0
side O 0
effects O 0
: O 0
results O 0
from O 0
the O 0
Multicenter O 0
Canadian O 0
Azidothymidine B-Chemical 0
Trial O 0
. O 0

To O 0
characterize O 0
the O 0
nature O 0
, O 0
time O 0
course O 0
and O 0
dose O 0
dependency O 0
of O 0
zidovudine B-Chemical 0
- O 0
related O 0
side O 0
effects O 0
, O 0
we O 0
undertook O 0
a O 0
multicenter O 0
, O 0
prospective O 0
, O 0
dose O 0
- O 0
range O 0
finding O 0
study O 0
. O 0

Our O 0
study O 0
group O 0
consisted O 0
of O 0
74 O 0
HIV O 0
- O 0
positive O 0
homosexual O 0
men O 0
belonging O 0
to O 0
groups O 0
II O 0
B O 0
, O 0
III O 0
and O 0
IV O 0
C2 O 0
from O 0
the O 0
Centers O 0
for O 0
Disease O 0
Control O 0
( O 0
CDC O 0
) O 0
classification O 0
of O 0
HIV B-Disease 0
disease I-Disease 0
. O 0

Following O 0
a O 0
3 O 0
- O 0
week O 0
observation O 0
period O 0
, O 0
volunteers O 0
were O 0
treated O 0
with O 0
zidovudine B-Chemical 0
600 O 0
mg O 0
/ O 0
day O 0
for O 0
18 O 0
weeks O 0
, O 0
900 O 0
mg O 0
/ O 0
day O 0
for O 0
9 O 0
weeks O 0
and O 0
1200 O 0
mg O 0
/ O 0
day O 0
for O 0
9 O 0
weeks O 0
, O 0
followed O 0
by O 0
a O 0
washout O 0
period O 0
of O 0
6 O 0
weeks O 0
after O 0
which O 0
they O 0
were O 0
re O 0
- O 0
started O 0
on O 0
1200 O 0
mg O 0
/ O 0
day O 0
or O 0
the O 0
highest O 0
tolerated O 0
dose O 0
at O 0
8 O 0
- O 0
hourly O 0
intervals O 0
. O 0

Subjects O 0
were O 0
randomly O 0
assigned O 0
to O 0
4 O 0
- O 0
hourly O 0
or O 0
8 O 0
- O 0
hourly O 0
regimens O 0
within O 0
CDC O 0
groups O 0
while O 0
taking O 0
600 O 0
and O 0
1200 O 0
mg O 0
/ O 0
day O 0
. O 0

Clinical O 0
and O 0
laboratory O 0
evaluations O 0
were O 0
performed O 0
at O 0
3 O 0
- O 0
week O 0
intervals O 0
. O 0

Symptomatic O 0
adverse O 0
effects O 0
were O 0
present O 0
in O 0
96 O 0
% O 0
of O 0
subjects O 0
, O 0
most O 0
commonly O 0
nausea B-Disease 0
( O 0
64 O 0
% O 0
) O 0
, O 0
fatigue B-Disease 0
( O 0
55 O 0
% O 0
) O 0
and O 0
headache B-Disease 0
( O 0
49 O 0
% O 0
) O 0
. O 0

These O 0
were O 0
generally O 0
self O 0
- O 0
limited O 0
, O 0
reappearing O 0
briefly O 0
at O 0
each O 0
dose O 0
increment O 0
. O 0

A O 0
decrease O 0
in O 0
hemoglobin O 0
occurred O 0
shortly O 0
after O 0
initiation O 0
of O 0
therapy O 0
. O 0

This O 0
was O 0
not O 0
dose O 0
dependent O 0
and O 0
reversed O 0
rapidly O 0
upon O 0
discontinuation O 0
of O 0
treatment O 0
. O 0

A O 0
red O 0
blood O 0
cell O 0
count O 0
decrease O 0
, O 0
a O 0
mean O 0
cell O 0
volume O 0
increase O 0
and O 0
a O 0
granulocyte O 0
count O 0
decrease O 0
developed O 0
early O 0
in O 0
a O 0
dose O 0
- O 0
independent O 0
fashion O 0
, O 0
reverting O 0
at O 0
least O 0
partially O 0
during O 0
the O 0
washout O 0
phase O 0
. O 0

The O 0
decrease O 0
in O 0
reticulocyte O 0
count O 0
was O 0
dose O 0
related O 0
between O 0
600 O 0
and O 0
900 O 0
mg O 0
/ O 0
day O 0
with O 0
no O 0
further O 0
change O 0
when O 0
the O 0
dose O 0
was O 0
escalated O 0
to O 0
1200 O 0
mg O 0
/ O 0
day O 0
. O 0

Bone O 0
marrow O 0
changes O 0
occurred O 0
rapidly O 0
as O 0
demonstrated O 0
by O 0
megaloblastosis B-Disease 0
in O 0
95 O 0
% O 0
of O 0
65 O 0
specimens O 0
at O 0
week O 0
18 O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

National O 0
project O 0
on O 0
the O 0
prevention O 0
of O 0
mother O 0
- O 0
to O 0
- O 0
infant O 0
infection B-Disease 0
by I-Disease 0
hepatitis I-Disease 0
B I-Disease 0
virus I-Disease 0
in O 0
Japan O 0
. O 0

In O 0
Japan O 0
, O 0
a O 0
nationwide O 0
prevention O 0
program O 0
against O 0
mother O 0
- O 0
to O 0
- O 0
infant O 0
infection B-Disease 0
by I-Disease 0
hepatitis I-Disease 0
B I-Disease 0
virus I-Disease 0
( O 0
HBV O 0
) O 0
started O 0
in O 0
1985 O 0
. O 0

This O 0
program O 0
consists O 0
of O 0
double O 0
screenings O 0
of O 0
pregnant O 0
women O 0
and O 0
prophylactic O 0
treatment O 0
to O 0
the O 0
infants O 0
born O 0
to O 0
both 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
and O 0
hepatitis B-Chemical 0
B I-Chemical 0
e I-Chemical 0
antigen I-Chemical 0
( O 0
HBeAg B-Chemical 0
) O 0
positive O 0
mothers O 0
. O 0

These O 0
infants O 0
are O 0
treated O 0
with O 0
two O 0
injections O 0
of 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
at O 0
least O 0
three O 0
injections O 0
of O 0
plasma O 0
derived O 0
hepatitis B-Chemical 0
B I-Chemical 0
vaccine I-Chemical 0
. O 0

We O 0
sent O 0
questionnaires O 0
about O 0
the O 0
numbers O 0
of O 0
each O 0
procedure O 0
or O 0
examination O 0
during O 0
nine O 0
months O 0
of O 0
investigation O 0
period O 0
to O 0
each O 0
local O 0
government O 0
in O 0
1986 O 0
and O 0
1987 O 0
. O 0

93 O 0
. O 0
4 O 0
% O 0
pregnant O 0
women O 0
had O 0
the O 0
chance O 0
to O 0
be O 0
examined O 0
for O 0
HBsAg B-Chemical 0
, O 0
and O 0
the O 0
positive O 0
rate O 0
was O 0
1 O 0
. O 0
4 O 0
to O 0
1 O 0
. O 0
5 O 0
% O 0
. O 0

The O 0
HBeAg B-Chemical 0
positive O 0
rate O 0
in O 0
HBsAg B-Chemical 0
positive O 0
was O 0
23 O 0
to O 0
26 O 0
% O 0
. O 0

The O 0
HBsAg B-Chemical 0
positive O 0
rate O 0
in O 0
neonates O 0
and O 0
in O 0
infants O 0
before O 0
two O 0
months O 0
were O 0
3 O 0
% O 0
and O 0
2 O 0
% O 0
respectively O 0
. O 0

Some O 0
problems O 0
may O 0
arise O 0
, O 0
because O 0
27 O 0
to O 0
30 O 0
% O 0
of O 0
infants O 0
need O 0
the O 0
fourth O 0
vaccination O 0
in O 0
some O 0
restricted O 0
areas O 0
. O 0

Involvement O 0
of O 0
the O 0
mu O 0
- O 0
opiate O 0
receptor O 0
in O 0
peripheral O 0
analgesia B-Disease 0
. O 0

The O 0
intradermal O 0
injection O 0
of O 0
mu O 0
( O 0
morphine B-Chemical 0
, O 0
Tyr B-Chemical 0
- I-Chemical 0
D I-Chemical 0
- I-Chemical 0
Ala I-Chemical 0
- I-Chemical 0
Gly I-Chemical 0
- I-Chemical 0
NMe I-Chemical 0
- I-Chemical 0
Phe I-Chemical 0
- I-Chemical 0
Gly I-Chemical 0
- I-Chemical 0
ol I-Chemical 0
and O 0
morphiceptin B-Chemical 0
) O 0
, O 0
kappa O 0
( O 0
trans B-Chemical 0
- I-Chemical 0
3 I-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
dichloro I-Chemical 0
- I-Chemical 0
N I-Chemical 0
- I-Chemical 0
methyl I-Chemical 0
- I-Chemical 0
N I-Chemical 0
[ I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
( I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
pyrrolidinyl I-Chemical 0
) I-Chemical 0
cyclohexyl I-Chemical 0
] I-Chemical 0
benzeneactemide I-Chemical 0
) O 0
and O 0
delta O 0
( O 0
[ B-Chemical 0
D I-Chemical 0
- I-Chemical 0
Pen2 I-Chemical 0
. I-Chemical 0
5 I-Chemical 0
] I-Chemical 0
- I-Chemical 0
enkephalin I-Chemical 0
and O 0
[ B-Chemical 0
D I-Chemical 0
- I-Chemical 0
Ser2 I-Chemical 0
] I-Chemical 0
- I-Chemical 0
[ I-Chemical 0
Leu I-Chemical 0
] I-Chemical 0
enkephalin I-Chemical 0
- I-Chemical 0
Thr I-Chemical 0
) O 0
selective O 0
opioid O 0
- O 0
agonists O 0
, O 0
by O 0
themselves O 0
, O 0
did O 0
not O 0
significantly O 0
affect O 0
the O 0
mechanical O 0
nociceptive O 0
threshold O 0
in O 0
the O 0
hindpaw O 0
of O 0
the O 0
rat O 0
. O 0

Intradermal O 0
injection O 0
of O 0
mu O 0
, O 0
but O 0
not O 0
delta O 0
or O 0
kappa O 0
opioid O 0
- O 0
agonists O 0
, O 0
however O 0
, O 0
produced O 0
dose O 0
- O 0
dependent O 0
inhibition O 0
of O 0
prostaglandin B-Chemical 0
E2 I-Chemical 0
- O 0
induced O 0
hyperalgesia B-Disease 0
. O 0

The O 0
analgesic O 0
effect O 0
of O 0
the O 0
mu O 0
- O 0
agonist O 0
morphine B-Chemical 0
was O 0
dose O 0
- O 0
dependently O 0
antagonized O 0
by O 0
naloxone B-Chemical 0
and O 0
prevented O 0
by O 0
co O 0
- O 0
injection O 0
of O 0
pertussis O 0
toxin O 0
. O 0

Morphine B-Chemical 0
did O 0
not O 0
, O 0
however O 0
, O 0
alter O 0
the O 0
hyperalgesia B-Disease 0
induced O 0
by O 0
8 B-Chemical 0
- I-Chemical 0
bromo I-Chemical 0
cyclic I-Chemical 0
adenosine I-Chemical 0
monophosphate I-Chemical 0
. O 0

We O 0
conclude O 0
that O 0
the O 0
analgesic O 0
action O 0
of O 0
opioids O 0
on O 0
the O 0
peripheral O 0
terminals O 0
of O 0
primary O 0
afferents O 0
is O 0
via O 0
a O 0
binding O 0
site O 0
with O 0
characteristics O 0
of O 0
the O 0
mu O 0
- O 0
opioid O 0
receptor O 0
and O 0
that O 0
this O 0
action O 0
is O 0
mediated O 0
by O 0
inhibition O 0
of O 0
the O 0
cyclic B-Chemical 0
adenosine I-Chemical 0
monophosphate I-Chemical 0
second O 0
messenger O 0
system O 0
. O 0

Involvement O 0
of O 0
locus O 0
coeruleus O 0
and O 0
noradrenergic O 0
neurotransmission O 0
in O 0
fentanyl B-Chemical 0
- O 0
induced O 0
muscular B-Disease 0
rigidity I-Disease 0
in O 0
the O 0
rat O 0
. O 0

Whereas O 0
muscular B-Disease 0
rigidity I-Disease 0
is O 0
a O 0
well O 0
- O 0
known O 0
side O 0
effect O 0
that O 0
is O 0
associated O 0
with O 0
high O 0
- O 0
dose O 0
fentanyl B-Chemical 0
anesthesia O 0
, O 0
a O 0
paucity O 0
of O 0
information O 0
exists O 0
with O 0
regard O 0
to O 0
its O 0
underlying O 0
mechanism O 0
( O 0
s O 0
) O 0
. O 0

We O 0
investigated O 0
in O 0
this O 0
study O 0
the O 0
possible O 0
engagement O 0
of O 0
locus O 0
coeruleus O 0
of O 0
the O 0
pons O 0
in O 0
this O 0
phenomenon O 0
, O 0
using O 0
male O 0
Sprague O 0
- O 0
Dawley O 0
rats O 0
anesthetized O 0
with O 0
ketamine B-Chemical 0
. O 0

Under O 0
proper O 0
control O 0
of O 0
respiration O 0
, O 0
body O 0
temperature O 0
and O 0
end O 0
- O 0
tidal O 0
CO2 B-Chemical 0
, O 0
intravenous O 0
administration O 0
of O 0
fentanyl B-Chemical 0
( O 0
50 O 0
or O 0
100 O 0
micrograms O 0
/ O 0
kg O 0
) O 0
consistently O 0
promoted O 0
an O 0
increase O 0
in O 0
electromyographic O 0
activity O 0
recorded O 0
from O 0
the O 0
gastrocnemius O 0
and O 0
abdominal O 0
rectus O 0
muscles O 0
. O 0

Such O 0
an O 0
induced O 0
muscular B-Disease 0
rigidity I-Disease 0
by O 0
the O 0
narcotic O 0
agent O 0
was O 0
significantly O 0
antagonized O 0
or O 0
even O 0
reduced O 0
by O 0
prior O 0
electrolytic O 0
lesions O 0
of O 0
the O 0
locus O 0
coeruleus O 0
or O 0
pretreatment O 0
with O 0
the O 0
alpha O 0
- O 0
adrenoceptor O 0
blocker O 0
, O 0
prazosin B-Chemical 0
. O 0

Microinjection O 0
of O 0
fentanyl B-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
micrograms O 0
/ O 0
50 O 0
nl O 0
) O 0
directly O 0
into O 0
this O 0
pontine O 0
nucleus O 0
, O 0
on O 0
the O 0
other O 0
hand O 0
, O 0
elicited O 0
discernible O 0
electromyographic O 0
excitation O 0
. O 0

It O 0
is O 0
speculated O 0
that O 0
the O 0
induction O 0
of O 0
muscular B-Disease 0
rigidity I-Disease 0
by O 0
fentanyl B-Chemical 0
may O 0
involve O 0
the O 0
coerulospinal O 0
noradrenergic O 0
fibers O 0
to O 0
the O 0
spinal O 0
motoneurons O 0
. O 0

Dexmedetomidine B-Chemical 0
, O 0
acting O 0
through O 0
central O 0
alpha O 0
- O 0
2 O 0
adrenoceptors O 0
, O 0
prevents O 0
opiate O 0
- O 0
induced O 0
muscle B-Disease 0
rigidity I-Disease 0
in O 0
the O 0
rat O 0
. O 0

The O 0
highly O 0
- O 0
selective O 0
alpha O 0
- O 0
2 O 0
adrenergic O 0
agonist O 0
dexmedetomidine B-Chemical 0
( O 0
D B-Chemical 0
- I-Chemical 0
MED I-Chemical 0
) O 0
is O 0
capable O 0
of O 0
inducing O 0
muscle B-Disease 0
flaccidity I-Disease 0
and O 0
anesthesia O 0
in O 0
rats O 0
and O 0
dogs O 0
. O 0

Intense O 0
generalized O 0
muscle B-Disease 0
rigidity I-Disease 0
is O 0
an O 0
undesirable O 0
side O 0
effect O 0
of O 0
potent O 0
opiate O 0
agonists O 0
. O 0

Although O 0
the O 0
neurochemistry O 0
of O 0
opiate O 0
- O 0
induced O 0
rigidity B-Disease 0
has O 0
yet O 0
to O 0
be O 0
fully O 0
elucidated O 0
, O 0
recent O 0
work O 0
suggests O 0
a O 0
role O 0
for O 0
a O 0
central O 0
adrenergic O 0
mechanism O 0
. O 0

In O 0
the O 0
present O 0
study O 0
, O 0
the O 0
authors O 0
determined O 0
if O 0
treatment O 0
with O 0
D B-Chemical 0
- I-Chemical 0
MED I-Chemical 0
prevents O 0
the O 0
muscle B-Disease 0
rigidity I-Disease 0
caused O 0
by O 0
high O 0
- O 0
dose O 0
alfentanil B-Chemical 0
anesthesia O 0
in O 0
the O 0
rat O 0
. O 0

Animals O 0
( O 0
n O 0
= O 0
42 O 0
) O 0
were O 0
treated O 0
intraperitoneally O 0
with O 0
one O 0
of O 0
the O 0
following O 0
six O 0
regimens O 0
: O 0
1 O 0
) O 0
L O 0
- O 0
MED O 0
( O 0
the O 0
inactive O 0
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D B-Chemical 0
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MED I-Chemical 0
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3 O 0
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D B-Chemical 0
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4 O 0
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D B-Chemical 0
- I-Chemical 0
MED I-Chemical 0
[ O 0
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kg O 0
] O 0
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the O 0
central O 0
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idazoxan B-Chemical 0
[ O 0
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D B-Chemical 0
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DG B-Chemical 0
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5128 I-Chemical 0
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Baseline O 0
electromyographic O 0
activity O 0
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Each O 0
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alfentanil B-Chemical 0
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0 O 0
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ALF B-Chemical 0
injection O 0
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increase O 0
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hindlimb O 0
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activity O 0
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MED O 0
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In O 0
contrast O 0
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D B-Chemical 0
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MED I-Chemical 0
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alfentanil B-Chemical 0
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muscle B-Disease 0
rigidity I-Disease 0
in O 0
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fashion O 0
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The O 0
small O 0
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D B-Chemical 0
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MED I-Chemical 0
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were O 0
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those O 0
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animals O 0
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. O 0

The O 0
high O 0
- O 0
dose O 0
D B-Chemical 0
- I-Chemical 0
MED I-Chemical 0
animals O 0
were O 0
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akinetic B-Disease 0
, O 0
and O 0
lacked O 0
a O 0
startle B-Disease 0
response O 0
during O 0
the O 0
entire O 0
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period O 0
. O 0
( O 0
ABSTRACT O 0
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AT O 0
250 O 0
WORDS O 0
) O 0

Some O 0
central O 0
effects O 0
of O 0
repeated O 0
treatment O 0
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fluvoxamine B-Chemical 0
. O 0

We O 0
investigated O 0
the O 0
effect O 0
of O 0
repeated O 0
treatment O 0
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fluvoxamine B-Chemical 0
, O 0
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serotonin B-Chemical 0
uptake O 0
inhibitor O 0
, O 0
on O 0
behavioral O 0
effects O 0
of O 0
dopaminomimetics O 0
and O 0
methoxamine B-Chemical 0
and O 0
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behavior O 0
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test O 0
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A O 0
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treatment O 0
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fluvoxamine B-Chemical 0
( O 0
twice O 0
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for O 0
14 O 0
days O 0
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The O 0
hyperactivity B-Disease 0
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. O 0

The O 0
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activity O 0
by O 0
intracerebroventricularly O 0
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methoxamine B-Chemical 0
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not O 0
affected O 0
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fluvoxamine B-Chemical 0
. O 0

Given O 0
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fluvoxamine B-Chemical 0
had O 0
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The O 0
results O 0
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fluvoxamine B-Chemical 0
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repeatedly O 0
acts O 0
differently O 0
than O 0
citalopram B-Chemical 0
, O 0
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serotonin B-Chemical 0
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, O 0
and O 0
differs O 0
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from O 0
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. O 0

Protective O 0
effect O 0
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BN B-Chemical 0
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bupivacaine B-Chemical 0
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. O 0

Administration O 0
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1 O 0
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5 O 0
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i O 0
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blood I-Disease 0
pressure I-Disease 0
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MBP I-Disease 0
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heart I-Disease 0
rate I-Disease 0
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HR I-Disease 0
) I-Disease 0
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67 O 0
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. O 0

Intravenous O 0
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of O 0
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HR I-Disease 0
. O 0

In O 0
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30 O 0
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5 O 0
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. O 0

When O 0
BN B-Chemical 0
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immediately O 0
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bupivacaine B-Chemical 0
( O 0
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reversion O 0
of O 0
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decrease B-Disease 0
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was O 0
observed O 0
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. O 0

A O 0
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BN B-Chemical 0
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. O 0

Since O 0
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BN B-Chemical 0
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clearly O 0
demonstrate O 0
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protective O 0
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BN B-Chemical 0
52021 I-Chemical 0
, O 0
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antagonist O 0
of O 0
PAF O 0
, O 0
against O 0
bupivacaine B-Chemical 0
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cardiovascular B-Disease 0
toxicity I-Disease 0
. O 0

Thus O 0
, O 0
consistent O 0
with O 0
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effect O 0
on O 0
heart O 0
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appears O 0
to O 0
be O 0
implicated O 0
in O 0
bupivacaine B-Chemical 0
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alterations I-Disease 0
. O 0

The O 0
epidemiology O 0
of O 0
the O 0
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flank B-Disease 0
pain I-Disease 0
syndrome O 0
from O 0
suprofen B-Chemical 0
. O 0

Suprofen B-Chemical 0
, O 0
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new O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
drug O 0
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was O 0
marketed O 0
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early O 0
1986 O 0
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. O 0

Until O 0
physicians O 0
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an O 0
unusual O 0
acute O 0
flank B-Disease 0
pain I-Disease 0
syndrome O 0
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the O 0
spontaneous O 0
reporting O 0
system O 0
, O 0
700 O 0
, O 0
000 O 0
persons O 0
used O 0
the O 0
drug O 0
in O 0
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States O 0
. O 0

Through O 0
August O 0
1986 O 0
, O 0
a O 0
total O 0
of O 0
163 O 0
cases O 0
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were O 0
reported O 0
. O 0

To O 0
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case O 0
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study O 0
was O 0
performed O 0
, O 0
comparing O 0
62 O 0
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the O 0
case O 0
patients O 0
who O 0
had O 0
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reported O 0
to O 0
the O 0
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system O 0
to O 0
185 O 0
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exposed O 0
control O 0
subjects O 0
who O 0
did O 0
not O 0
have O 0
the O 0
syndrome O 0
. O 0

Case O 0
patients O 0
were O 0
more O 0
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men O 0
( O 0
odds O 0
ratio O 0
, O 0
3 O 0
. O 0
8 O 0
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% O 0
confidence O 0
interval O 0
, O 0
1 O 0
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2 O 0
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suffer O 0
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hay B-Disease 0
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and O 0
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( O 0
odds O 0
ratio O 0
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3 O 0
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4 O 0
; O 0
95 O 0
% O 0
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1 O 0
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9 O 0
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1 O 0
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use O 0
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ratio O 0
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4 O 0
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4 O 0
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95 O 0
% O 0
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1 O 0
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1 O 0
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5 O 0
) O 0
. O 0

Possible O 0
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young O 0
age O 0
, O 0
concurrent O 0
use O 0
of O 0
other O 0
analgesic O 0
agents O 0
( O 0
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ibuprofen B-Chemical 0
) O 0
, O 0
preexisting O 0
renal B-Disease 0
disease I-Disease 0
, O 0
a O 0
history O 0
of O 0
kidney B-Disease 0
stones I-Disease 0
, O 0
a O 0
history O 0
of O 0
gout B-Disease 0
, O 0
a O 0
recent O 0
increase O 0
in O 0
activity O 0
, O 0
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increase O 0
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sun O 0
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. O 0

These O 0
were O 0
findings O 0
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were O 0
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did O 0
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statistical O 0
significance O 0
. O 0

These O 0
findings O 0
are O 0
consistent O 0
with O 0
the O 0
postulated O 0
mechanism O 0
for O 0
this O 0
unusual O 0
syndrome O 0
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acute O 0
diffuse O 0
crystallization O 0
of O 0
uric B-Chemical 0
acid I-Chemical 0
in O 0
renal O 0
tubules O 0
. O 0

Phlorizin B-Chemical 0
- O 0
induced O 0
glycosuria B-Disease 0
does O 0
not O 0
prevent O 0
gentamicin B-Chemical 0
nephrotoxicity B-Disease 0
in O 0
rats O 0
. O 0

Because O 0
rats O 0
with O 0
streptozotocin B-Chemical 0
- O 0
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diabetes B-Disease 0
mellitus I-Disease 0
( O 0
DM B-Disease 0
) O 0
have O 0
a O 0
high O 0
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glycosuria B-Disease 0
of O 0
10 O 0
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12 O 0
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day O 0
) O 0
, O 0
we O 0
have O 0
suggested O 0
that O 0
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may O 0
in O 0
part O 0
be O 0
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for O 0
their O 0
resistance O 0
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gentamicin B-Chemical 0
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induced O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
( O 0
ARF B-Disease 0
) O 0
. O 0

The O 0
protection O 0
from O 0
gentamicin B-Chemical 0
nephrotoxicity B-Disease 0
was O 0
studied O 0
in O 0
non O 0
- O 0
diabetic B-Disease 0
rats O 0
with O 0
chronic O 0
solute O 0
diuresis O 0
induced O 0
by O 0
blockage O 0
of O 0
tubular O 0
glucose B-Chemical 0
reabsorption O 0
with O 0
phlorizin B-Chemical 0
( O 0
P B-Chemical 0
) O 0
. O 0

DM B-Disease 0
rats O 0
with O 0
mild O 0
glycosuria B-Disease 0
( O 0
similar O 0
in O 0
degree O 0
to O 0
that O 0
of O 0
the O 0
P B-Chemical 0
treated O 0
animals O 0
) O 0
were O 0
also O 0
studied O 0
. O 0

Unanesthetized O 0
adult O 0
female O 0
, O 0
Sprague O 0
- O 0
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rats O 0
were O 0
divided O 0
in O 0
four O 0
groups O 0
and O 0
studied O 0
for O 0
15 O 0
days O 0
. O 0

Group O 0
1 O 0
( O 0
P B-Chemical 0
alone O 0
) O 0
received O 0
P B-Chemical 0
, O 0
360 O 0
mg O 0
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day O 0
, O 0
for O 0
15 O 0
days O 0
; O 0
Group O 0
II O 0
( O 0
P B-Chemical 0
+ O 0
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) O 0
; O 0
Group O 0
III O 0
( O 0
gentamicin B-Chemical 0
alone O 0
) O 0
and O 0
Group O 0
IV O 0
( O 0
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DM B-Disease 0
+ O 0
gentamicin B-Chemical 0
) O 0
. O 0

Nephrotoxic B-Disease 0
doses O 0
( O 0
40 O 0
mg O 0
/ O 0
kg O 0
body O 0
wt O 0
/ O 0
day O 0
) O 0
of O 0
gentamicin B-Chemical 0
were O 0
injected O 0
during O 0
the O 0
last O 0
nine O 0
days O 0
of O 0
study O 0
to O 0
the O 0
animals O 0
of O 0
groups O 0
II O 0
to O 0
IV O 0
. O 0

In O 0
Group O 0
I O 0
, O 0
P B-Chemical 0
induced O 0
a O 0
moderate O 0
and O 0
stable O 0
glycosuria B-Disease 0
( O 0
3 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
g O 0
/ O 0
day O 0
, O 0
SE O 0
) O 0
, O 0
and O 0
no O 0
functional O 0
or O 0
morphologic O 0
evidence O 0
of O 0
renal B-Disease 0
dysfunction I-Disease 0
( O 0
baseline O 0
CCr O 0
2 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
ml O 0
/ O 0
min O 0
, O 0
undetectable O 0
lysozymuria O 0
) O 0
or O 0
damage O 0
( O 0
tubular B-Disease 0
necrosis I-Disease 0
score O 0
[ O 0
maximum O 0
4 O 0
] O 0
, O 0
zero O 0
) O 0
. O 0

In O 0
Group O 0
II O 0
, O 0
P B-Chemical 0
did O 0
not O 0
prevent O 0
gentamicin B-Chemical 0
- O 0
ARF B-Disease 0
( O 0
maximal O 0
decrease O 0
in O 0
CCr O 0
at O 0
day O 0
9 O 0
. O 0
89 O 0
% O 0
, O 0
P B-Chemical 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
; O 0
peak O 0
lysozymuria O 0
, O 0
1863 O 0
+ O 0
/ O 0
- O 0
321 O 0
micrograms O 0
/ O 0
day O 0
; O 0
and O 0
tubular B-Disease 0
necrosis I-Disease 0
score O 0
, O 0
3 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
) O 0
. O 0

These O 0
values O 0
were O 0
not O 0
different O 0
from O 0
those O 0
of O 0
Group O 0
III O 0
: O 0
maximal O 0
decrease O 0
in O 0
CCr O 0
73 O 0
% O 0
( O 0
P B-Chemical 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
) O 0
; O 0
lysozymuria O 0
, O 0
2147 O 0
+ O 0
/ O 0
- O 0
701 O 0
micrograms O 0
/ O 0
day O 0
; O 0
tubular B-Disease 0
necrosis I-Disease 0
score O 0
, O 0
3 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Catalepsy B-Disease 0
induced O 0
by O 0
combinations O 0
of O 0
ketamine B-Chemical 0
and O 0
morphine B-Chemical 0
: O 0
potentiation O 0
, O 0
antagonism O 0
, O 0
tolerance O 0
and O 0
cross O 0
- O 0
tolerance O 0
in O 0
the O 0
rat O 0
. O 0

Previous O 0
studies O 0
demonstrated O 0
that O 0
both O 0
ketamine B-Chemical 0
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Pre O 0
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The O 0
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There O 0
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Latency O 0
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Naloxone B-Chemical 0
inhibited O 0
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effects O 0
. O 0

The O 0
degree O 0
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time O 0
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of O 0
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daily O 0
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Rats O 0
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ketamine B-Chemical 0
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combinations O 0
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cross O 0
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morphine B-Chemical 0
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ketamine B-Chemical 0
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While O 0
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, O 0
asymmetry O 0
of O 0
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tolerance O 0
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a O 0
widely O 0
- O 0
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ID50 O 0
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would O 0
argue O 0
against O 0
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site O 0
. O 0

Hydrocortisone B-Chemical 0
- O 0
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hypertension B-Disease 0
in O 0
humans O 0
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responsiveness O 0
and O 0
sympathetic O 0
function O 0
. O 0

Oral O 0
hydrocortisone B-Chemical 0
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pressure O 0
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enhances O 0
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responsiveness O 0
in O 0
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. O 0

We O 0
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effects O 0
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1 O 0
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day O 0
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blood O 0
pressure O 0
, O 0
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output O 0
, O 0
total O 0
peripheral O 0
resistance O 0
, O 0
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resistance O 0
, O 0
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norepinephrine B-Chemical 0
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to O 0
plasma O 0
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eight O 0
healthy O 0
male O 0
volunteers O 0
. O 0

Although O 0
diastolic O 0
blood O 0
pressure O 0
remained O 0
unchanged O 0
, O 0
systolic O 0
blood O 0
pressure O 0
increased O 0
from O 0
119 O 0
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mm O 0
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( O 0
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3 O 0
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cardiac I-Disease 0
output I-Disease 0
( O 0
5 O 0
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85 O 0
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7 O 0
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l O 0
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Total O 0
peripheral O 0
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resistance O 0
fell O 0
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1 O 0
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Resting O 0
forearm O 0
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resistance O 0
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, O 0
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the O 0
reflex O 0
response O 0
to O 0
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test O 0
was O 0
accentuated O 0
, O 0
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in O 0
resistance O 0
increasing O 0
from O 0
10 O 0
. O 0
5 O 0
mm O 0
Hg O 0
/ O 0
ml O 0
/ O 0
100 O 0
ml O 0
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min O 0
( O 0
R O 0
units O 0
) O 0
before O 0
treatment O 0
to O 0
32 O 0
. O 0
6 O 0
R O 0
units O 0
after O 0
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6 O 0
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4 O 0
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p O 0
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than O 0
0 O 0
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) O 0
. O 0

The O 0
rise O 0
in O 0
forearm O 0
vascular O 0
resistance O 0
accompanying O 0
intra O 0
- O 0
arterial O 0
norepinephrine B-Chemical 0
( O 0
25 O 0
, O 0
50 O 0
, O 0
and O 0
100 O 0
ng O 0
/ O 0
min O 0
) O 0
was O 0
also O 0
significantly O 0
greater O 0
after O 0
hydrocortisone B-Chemical 0
, O 0
increasing O 0
from O 0
an O 0
average O 0
of O 0
14 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
4 O 0
R O 0
units O 0
before O 0
treatment O 0
to O 0
35 O 0
. O 0
1 O 0
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/ O 0
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5 O 0
. O 0
5 O 0
R O 0
units O 0
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hydrocortisone B-Chemical 0
( O 0
SED O 0
+ O 0
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6 O 0
. O 0
0 O 0
, O 0
p O 0
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than O 0
0 O 0
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05 O 0
) O 0
. O 0

A O 0
shift O 0
to O 0
the O 0
left O 0
in O 0
the O 0
dose O 0
- O 0
response O 0
relation O 0
and O 0
fall O 0
in O 0
threshold O 0
suggested O 0
increased O 0
sensitivity O 0
to O 0
norepinephrine B-Chemical 0
after O 0
treatment O 0
. O 0

Measurement O 0
of O 0
resting O 0
norepinephrine B-Chemical 0
spillover O 0
rate O 0
to O 0
plasma O 0
and O 0
norepinephrine B-Chemical 0
uptake O 0
indicated O 0
that O 0
overall O 0
resting O 0
sympathetic O 0
nervous O 0
system O 0
activity O 0
was O 0
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. O 0

The O 0
rise B-Disease 0
in I-Disease 0
resting I-Disease 0
blood I-Disease 0
pressure I-Disease 0
with O 0
hydrocortisone B-Chemical 0
is O 0
associated O 0
with O 0
an O 0
increased B-Disease 0
cardiac I-Disease 0
output I-Disease 0
( O 0
presumably O 0
due O 0
to O 0
increased O 0
blood O 0
volume 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

Neuromuscular B-Disease 0
blockade I-Disease 0
with O 0
magnesium B-Chemical 0
sulfate I-Chemical 0
and O 0
nifedipine B-Chemical 0
. O 0

A O 0
patient O 0
who O 0
received O 0
tocolysis O 0
with O 0
nifedipine B-Chemical 0
developed O 0
neuromuscular B-Disease 0
blockade I-Disease 0
after O 0
500 O 0
mg O 0
of O 0
magnesium B-Chemical 0
sulfate I-Chemical 0
was O 0
administered O 0
. O 0

This O 0
reaction O 0
demonstrates O 0
that O 0
nifedipine B-Chemical 0
can O 0
seriously O 0
potentiate O 0
the O 0
toxicity B-Disease 0
of O 0
magnesium B-Chemical 0
. O 0

Caution O 0
should O 0
be O 0
exercised O 0
when O 0
these O 0
two O 0
tocolytics O 0
are O 0
combined O 0
. O 0

Chronic O 0
carbamazepine B-Chemical 0
inhibits O 0
the O 0
development O 0
of O 0
local O 0
anesthetic O 0
seizures B-Disease 0
kindled O 0
by O 0
cocaine B-Chemical 0
and O 0
lidocaine B-Chemical 0
. O 0

The O 0
effects O 0
of O 0
carbamazepine B-Chemical 0
( O 0
CBZ B-Chemical 0
) O 0
treatment O 0
on O 0
local O 0
anesthetic O 0
- O 0
kindled O 0
seizures B-Disease 0
and O 0
lethality O 0
were O 0
evaluated O 0
in O 0
different O 0
stages O 0
of O 0
the O 0
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process O 0
and O 0
under O 0
different O 0
methods O 0
of O 0
CBZ B-Chemical 0
administration O 0
. O 0

Chronic O 0
oral O 0
CBZ B-Chemical 0
inhibited O 0
the O 0
development O 0
of O 0
both O 0
lidocaine B-Chemical 0
- O 0
and O 0
cocaine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
, O 0
but O 0
had O 0
little O 0
effect O 0
on O 0
the O 0
fully O 0
developed O 0
local O 0
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seizures B-Disease 0
. O 0

Chronic O 0
CBZ B-Chemical 0
also O 0
decreased O 0
the O 0
incidence O 0
of O 0
seizure B-Disease 0
- O 0
related O 0
mortality O 0
in O 0
the O 0
cocaine B-Chemical 0
- O 0
injected O 0
rats O 0
. O 0

Acute O 0
CBZ B-Chemical 0
over O 0
a O 0
range O 0
of O 0
doses O 0
( O 0
15 O 0
- O 0
50 O 0
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/ O 0
kg O 0
) O 0
had O 0
no O 0
effect O 0
on O 0
completed O 0
lidocaine B-Chemical 0
- O 0
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or O 0
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cocaine B-Chemical 0
- O 0
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seizures B-Disease 0
. O 0

Repeated O 0
i O 0
. O 0
p O 0
. O 0
injection O 0
of O 0
CBZ B-Chemical 0
( O 0
15 O 0
mg O 0
/ O 0
kg O 0
) O 0
also O 0
was O 0
without O 0
effect O 0
on O 0
the O 0
development O 0
of O 0
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- O 0
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- O 0
kindled O 0
seizures B-Disease 0
. O 0

The O 0
differential O 0
effects O 0
of O 0
CBZ B-Chemical 0
depending O 0
upon O 0
stage O 0
of O 0
seizure B-Disease 0
development O 0
suggest O 0
that O 0
distinct O 0
mechanisms O 0
underlie O 0
the O 0
development O 0
versus O 0
maintenance O 0
of O 0
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seizures B-Disease 0
. O 0

The O 0
effectiveness O 0
of O 0
chronic O 0
but O 0
not O 0
repeated O 0
, O 0
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injections O 0
of O 0
CBZ B-Chemical 0
suggests O 0
that O 0
different O 0
biochemical O 0
consequences O 0
result O 0
from O 0
the O 0
different O 0
treatment O 0
regimens O 0
. O 0

The O 0
possible O 0
utility O 0
of O 0
chronic O 0
CBZ B-Chemical 0
in O 0
preventing O 0
the O 0
development O 0
of O 0
toxic O 0
side O 0
effects O 0
in O 0
human O 0
cocaine B-Chemical 0
users O 0
is O 0
suggested O 0
by O 0
these O 0
data O 0
, O 0
but O 0
remains O 0
to O 0
be O 0
directly O 0
evaluated O 0
. O 0

Magnetic O 0
resonance O 0
imaging O 0
of O 0
cerebral O 0
venous B-Disease 0
thrombosis I-Disease 0
secondary O 0
to O 0
" O 0
low O 0
- O 0
dose O 0
" O 0
birth O 0
control O 0
pills O 0
. O 0

The O 0
clinical O 0
and O 0
radiographic O 0
features O 0
of O 0
cerebral O 0
deep B-Disease 0
venous I-Disease 0
thrombosis I-Disease 0
in O 0
a O 0
21 O 0
- O 0
year O 0
- O 0
old O 0
white O 0
woman O 0
are O 0
presented O 0
. O 0

This O 0
nulliparous O 0
patient O 0
presented O 0
with O 0
relatively O 0
mild O 0
clinical O 0
symptoms O 0
and O 0
progressing O 0
mental O 0
status O 0
changes O 0
. O 0

The O 0
only O 0
known O 0
risk O 0
factor O 0
was O 0
" O 0
low O 0
- O 0
dose O 0
" O 0
oral B-Chemical 0
contraceptive I-Chemical 0
pills O 0
. O 0

The O 0
magnetic O 0
resonance O 0
image O 0
( O 0
MRI O 0
) O 0
showed O 0
increased O 0
signal O 0
intensity O 0
from O 0
the O 0
internal O 0
cerebral O 0
veins O 0
, O 0
vein O 0
of O 0
Galen O 0
, O 0
and O 0
straight O 0
sinus O 0
. O 0

The O 0
diagnosis O 0
was O 0
confirmed O 0
by O 0
arterial O 0
angiography O 0
. O 0

Beta O 0
- O 0
2 O 0
- O 0
adrenoceptor O 0
- O 0
mediated O 0
hypokalemia B-Disease 0
and O 0
its O 0
abolishment O 0
by O 0
oxprenolol B-Chemical 0
. O 0

The O 0
time O 0
course O 0
and O 0
concentration O 0
- O 0
effect O 0
relationship O 0
of O 0
terbutaline B-Chemical 0
- O 0
induced O 0
hypokalemia B-Disease 0
was O 0
studied O 0
, O 0
using O 0
computer O 0
- O 0
aided O 0
pharmacokinetic O 0
- O 0
dynamic O 0
modeling O 0
. O 0

Subsequently O 0
we O 0
investigated O 0
the O 0
efficacy O 0
of O 0
oxprenolol B-Chemical 0
in O 0
antagonizing O 0
such O 0
hypokalemia B-Disease 0
, O 0
together O 0
with O 0
the O 0
pharmacokinetic O 0
interaction O 0
between O 0
both O 0
drugs O 0
. O 0

Six O 0
healthy O 0
subjects O 0
were O 0
given O 0
a O 0
0 O 0
. O 0
5 O 0
mg O 0
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dose O 0
of O 0
terbutaline B-Chemical 0
on O 0
two O 0
occasions O 0
: O 0
1 O 0
hour O 0
after O 0
oral O 0
administration O 0
of O 0
a O 0
placebo O 0
and O 0
1 O 0
hour O 0
after O 0
80 O 0
mg O 0
oxprenolol B-Chemical 0
orally O 0
. O 0

In O 0
the O 0
7 O 0
- O 0
hour O 0
period O 0
after O 0
terbutaline B-Chemical 0
administration O 0
, O 0
plasma O 0
samples O 0
were O 0
taken O 0
for O 0
determination O 0
of O 0
plasma O 0
potassium B-Chemical 0
levels O 0
and O 0
drug O 0
concentrations O 0
. O 0

The O 0
sigmoid O 0
Emax O 0
model O 0
offered O 0
a O 0
good O 0
description O 0
of O 0
the O 0
relation O 0
between O 0
terbutaline B-Chemical 0
concentrations O 0
and O 0
potassium B-Chemical 0
effects O 0
. O 0

Oxprenolol B-Chemical 0
caused O 0
decreases O 0
of O 0
65 O 0
% O 0
and O 0
56 O 0
% O 0
of O 0
terbutaline B-Chemical 0
volume O 0
of O 0
distribution O 0
and O 0
clearance O 0
, O 0
respectively O 0
, O 0
and O 0
an O 0
increase O 0
of O 0
130 O 0
% O 0
of O 0
its O 0
AUC O 0
. O 0

In O 0
spite O 0
of O 0
higher O 0
terbutaline B-Chemical 0
concentrations O 0
after O 0
oxprenolol B-Chemical 0
pretreatment O 0
, O 0
the O 0
hypokalemia B-Disease 0
was O 0
almost O 0
completely O 0
antagonized O 0
by O 0
the O 0
beta O 0
2 O 0
- O 0
blocking O 0
action O 0
. O 0

A O 0
dystonia B-Disease 0
- O 0
like O 0
syndrome O 0
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neuropeptide O 0
( O 0
MSH B-Chemical 0
/ O 0
ACTH B-Chemical 0
) O 0
stimulation O 0
of O 0
the O 0
rat O 0
locus O 0
ceruleus O 0
. O 0

The O 0
movement B-Disease 0
disorder I-Disease 0
investigated O 0
in O 0
these O 0
studies O 0
has O 0
some O 0
features O 0
in O 0
common O 0
with O 0
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idiopathic O 0
dystonia B-Disease 0
, O 0
and O 0
information O 0
obtained O 0
in O 0
these O 0
studies O 0
may O 0
be O 0
of O 0
potential O 0
clinical O 0
benefit O 0
. O 0

The O 0
present O 0
experimental O 0
results O 0
indicated O 0
that O 0
peptidergic O 0
stimulation O 0
of O 0
the O 0
LC O 0
resulted O 0
in O 0
a O 0
NE O 0
- O 0
mediated O 0
inhibition O 0
of O 0
cerebellar O 0
Purkinje O 0
cells O 0
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at O 0
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- O 0
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. O 0

However O 0
, O 0
it O 0
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to O 0
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a O 0
) O 0
what O 0
receptors O 0
were O 0
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by O 0
the O 0
ACTH B-Chemical 0
N O 0
- O 0
terminal O 0
fragments O 0
at O 0
the O 0
LC O 0
that O 0
resulted O 0
in O 0
this O 0
disorder O 0
; O 0
( O 0
b O 0
) O 0
whether O 0
NE O 0
, O 0
released O 0
onto O 0
Purkinje O 0
cell O 0
synapses O 0
located O 0
at O 0
terminals O 0
of O 0
the O 0
ceruleo O 0
- O 0
cerebellar O 0
pathway O 0
, O 0
did O 0
indeed O 0
cause O 0
the O 0
long O 0
- O 0
term O 0
depression B-Disease 0
at O 0
Purkinje O 0
cell O 0
synapses O 0
( O 0
previously O 0
described O 0
by O 0
others O 0
) O 0
that O 0
resulted O 0
in O 0
the O 0
long O 0
duration O 0
of O 0
the O 0
movement B-Disease 0
disorder I-Disease 0
; O 0
( O 0
c O 0
) O 0
whether O 0
the O 0
inhibition O 0
of O 0
inhibitory O 0
Purkinje O 0
cells O 0
resulted O 0
in O 0
disinhibition O 0
or O 0
increased O 0
excitability O 0
of O 0
the O 0
unilateral O 0
cerebellar O 0
fastigial O 0
or O 0
interpositus O 0
nuclei O 0
, O 0
the O 0
output O 0
targets O 0
of O 0
the O 0
Purkinje O 0
cell O 0
axons O 0
, O 0
that O 0
may O 0
have O 0
been O 0
an O 0
important O 0
contributing O 0
factor O 0
to O 0
this O 0
disorder O 0
. O 0

These O 0
questions O 0
are O 0
currently O 0
being O 0
investigated O 0
. O 0

Enhanced O 0
stimulus O 0
- O 0
induced O 0
neurotransmitter O 0
overflow O 0
in O 0
epinephrine B-Chemical 0
- O 0
induced O 0
hypertensive B-Disease 0
rats O 0
is O 0
not O 0
mediated O 0
by O 0
prejunctional O 0
beta O 0
- O 0
adrenoceptor O 0
activation O 0
. O 0

The O 0
present O 0
study O 0
examines O 0
the O 0
effect O 0
of O 0
6 O 0
- O 0
day O 0
epinephrine B-Chemical 0
treatment O 0
( O 0
100 O 0
micrograms O 0
/ O 0
kg O 0
per O 0
h O 0
, O 0
s O 0
. O 0
c O 0
. O 0
) O 0
on O 0
stimulus O 0
- O 0
induced O 0
( O 0
1 O 0
Hz O 0
) O 0
endogenous O 0
neurotransmitter O 0
overflow O 0
from O 0
the O 0
isolated O 0
perfused O 0
kidney O 0
of O 0
vehicle O 0
- O 0
and O 0
epinephrine B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

Renal O 0
catecholamine B-Chemical 0
stores O 0
and O 0
stimulus O 0
- O 0
induced O 0
overflow O 0
in O 0
the O 0
vehicle O 0
- O 0
treated O 0
group O 0
consisted O 0
of O 0
norepinephrine B-Chemical 0
only O 0
. O 0

However O 0
, O 0
epinephrine B-Chemical 0
treatment O 0
resulted O 0
in O 0
the O 0
incorporation O 0
of O 0
epinephrine B-Chemical 0
into O 0
renal O 0
catecholamine B-Chemical 0
stores O 0
such O 0
that O 0
approximately O 0
40 O 0
% O 0
of O 0
the O 0
catecholamine B-Chemical 0
present O 0
was O 0
epinephrine B-Chemical 0
while O 0
the O 0
norepinephrine B-Chemical 0
content O 0
was O 0
reduced O 0
by O 0
a O 0
similar O 0
degree O 0
. O 0

Total O 0
tissue O 0
catecholamine B-Chemical 0
content O 0
of O 0
the O 0
kidney O 0
on O 0
a O 0
molar O 0
basis O 0
was O 0
unchanged O 0
. O 0

Stimulus O 0
- O 0
induced O 0
fractional O 0
overflow O 0
of O 0
neurotransmitter O 0
from O 0
the O 0
epinephrine B-Chemical 0
- O 0
treated O 0
kidneys O 0
was O 0
approximately O 0
twice O 0
normal O 0
and O 0
consisted O 0
of O 0
both O 0
norepinephrine B-Chemical 0
and O 0
epinephrine B-Chemical 0
in O 0
proportions O 0
similar O 0
to O 0
those O 0
found O 0
in O 0
the O 0
kidney O 0
. O 0

This O 0
difference O 0
in O 0
fractional O 0
overflow O 0
between O 0
groups O 0
was O 0
not O 0
affected O 0
by O 0
neuronal O 0
and O 0
extraneuronal O 0
uptake O 0
blockade O 0
. O 0

Propranolol B-Chemical 0
had O 0
no O 0
effect O 0
on O 0
stimulus O 0
- O 0
induced O 0
overflow O 0
in O 0
either O 0
group O 0
. O 0

Phentolamine B-Chemical 0
increased O 0
stimulus O 0
- O 0
induced O 0
overflow O 0
in O 0
both O 0
groups O 0
although O 0
the O 0
increment O 0
in O 0
overflow O 0
was O 0
greater O 0
in O 0
the O 0
epinephrine B-Chemical 0
- O 0
treated O 0
group O 0
. O 0

In O 0
conclusion O 0
, O 0
chronic O 0
epinephrine B-Chemical 0
treatment O 0
results O 0
in O 0
enhanced O 0
fractional O 0
neurotransmitter O 0
overflow O 0
. O 0

However O 0
, O 0
neither O 0
alterations O 0
in O 0
prejunctional O 0
beta O 0
- O 0
adrenoceptor O 0
influences O 0
nor O 0
alterations O 0
in O 0
neuronal O 0
and O 0
extraneuronal O 0
uptake O 0
mechanisms O 0
appear O 0
to O 0
be O 0
responsible O 0
for O 0
this O 0
alteration O 0
. O 0

Furthermore O 0
, O 0
data O 0
obtained O 0
with O 0
phentolamine B-Chemical 0
alone O 0
do O 0
not O 0
suggest O 0
alpha O 0
- O 0
adrenoceptor O 0
desensitization O 0
as O 0
the O 0
cause O 0
of O 0
the O 0
enhanced O 0
neurotransmitter O 0
overflow O 0
after O 0
epinephrine B-Chemical 0
treatment O 0
. O 0

GABA B-Chemical 0
involvement O 0
in O 0
naloxone B-Chemical 0
induced O 0
reversal O 0
of O 0
respiratory B-Disease 0
paralysis I-Disease 0
produced O 0
by O 0
thiopental B-Chemical 0
. O 0

No O 0
agent O 0
is O 0
yet O 0
available O 0
to O 0
reverse O 0
respiratory B-Disease 0
paralysis I-Disease 0
produced O 0
by O 0
CNS O 0
depressants O 0
, O 0
such O 0
as O 0
general O 0
anesthetics O 0
. O 0

In O 0
this O 0
study O 0
naloxone B-Chemical 0
reversed O 0
respiratory B-Disease 0
paralysis I-Disease 0
induced O 0
by O 0
thiopental B-Chemical 0
in O 0
rats O 0
. O 0

25 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
v O 0
. O 0
thiopental B-Chemical 0
produced O 0
anesthesia O 0
without O 0
altering O 0
respiratory O 0
rate O 0
, O 0
increased O 0
GABA B-Chemical 0
, O 0
decreased O 0
glutamate B-Chemical 0
, O 0
and O 0
had O 0
no O 0
effect O 0
on O 0
aspartate B-Chemical 0
or O 0
glycine B-Chemical 0
levels O 0
compared O 0
to O 0
controls O 0
in O 0
rat O 0
cortex O 0
and O 0
brain O 0
stem O 0
. O 0

Pretreatment O 0
of O 0
rats O 0
with O 0
thiosemicarbazide B-Chemical 0
for O 0
30 O 0
minutes O 0
abolished O 0
the O 0
anesthetic O 0
action O 0
as O 0
well O 0
as O 0
the O 0
respiratory O 0
depressant O 0
action O 0
of O 0
thiopental B-Chemical 0
. O 0

50 O 0
mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
v O 0
. O 0
thiopental B-Chemical 0
produced O 0
respiratory B-Disease 0
arrest I-Disease 0
with O 0
further O 0
increase O 0
in O 0
GABA B-Chemical 0
and O 0
decrease O 0
in O 0
glutamate B-Chemical 0
again O 0
in O 0
cortex O 0
and O 0
brain O 0
stem O 0
without O 0
affecting O 0
any O 0
of O 0
the O 0
amino B-Chemical 0
acids I-Chemical 0
studied O 0
in O 0
four O 0
regions O 0
of O 0
rat O 0
brain O 0
. O 0

Naloxone B-Chemical 0
( O 0
2 O 0
. 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
reversed O 0
respiratory B-Disease 0
paralysis I-Disease 0
, O 0
glutamate B-Chemical 0
and O 0
GABA B-Chemical 0
levels O 0
to O 0
control O 0
values O 0
in O 0
brain O 0
stem O 0
and O 0
cortex O 0
with O 0
no O 0
changes O 0
in O 0
caudate O 0
or O 0
cerebellum O 0
. O 0

These O 0
data O 0
suggest O 0
naloxone B-Chemical 0
reverses O 0
respiratory B-Disease 0
paralysis I-Disease 0
produced O 0
by O 0
thiopental B-Chemical 0
and O 0
involves O 0
GABA B-Chemical 0
in O 0
its O 0
action O 0
. O 0

Diazepam B-Chemical 0
facilitates O 0
reflex O 0
bradycardia B-Disease 0
in O 0
conscious O 0
rats O 0
. O 0

The O 0
effects O 0
of O 0
diazepam B-Chemical 0
on O 0
cardiovascular O 0
function O 0
were O 0
assessed O 0
in O 0
conscious O 0
rats O 0
. O 0

Intravenous O 0
administration O 0
of O 0
diazepam B-Chemical 0
( O 0
1 O 0
- O 0
30 O 0
mg O 0
kg O 0
- O 0
1 O 0
) O 0
produced 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

Also O 0
, O 0
reflex O 0
bradycardia B-Disease 0
was O 0
produced O 0
in O 0
rats O 0
by O 0
intravenous O 0
infusion O 0
of O 0
adrenaline B-Chemical 0
( O 0
1 O 0
. O 0
25 O 0
- O 0
2 O 0
. O 0
5 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
) O 0
. O 0

Intravenous O 0
pretreatment O 0
of O 0
the O 0
rats O 0
with O 0
diazepam B-Chemical 0
, O 0
although O 0
causing O 0
no O 0
change O 0
in O 0
the O 0
adrenaline B-Chemical 0
- O 0
induced O 0
pressor O 0
effect O 0
, O 0
did O 0
enhance O 0
the O 0
adrenaline B-Chemical 0
- O 0
induced O 0
reflex O 0
bradycardia B-Disease 0
. O 0

However O 0
, O 0
the O 0
diazepam B-Chemical 0
enhancement O 0
of O 0
adrenaline B-Chemical 0
- O 0
induced O 0
reflex O 0
bradycardia B-Disease 0
was O 0
antagonized O 0
by O 0
pretreatment O 0
of O 0
rats O 0
with O 0
an O 0
intravenous O 0
dose O 0
of O 0
picrotoxin B-Chemical 0
( O 0
an O 0
agent O 0
blocks O 0
chloride B-Chemical 0
channels O 0
by O 0
binding O 0
to O 0
sites O 0
associated O 0
with O 0
the O 0
benzodiazepine B-Chemical 0
- O 0
GABA B-Chemical 0
- O 0
chloride B-Chemical 0
channel O 0
macromolecular O 0
complex O 0
) O 0
. O 0

The O 0
data O 0
indicate O 0
that O 0
diazepam B-Chemical 0
acts O 0
through O 0
the O 0
benzodiazepine B-Chemical 0
- O 0
GABA B-Chemical 0
- O 0
chloride B-Chemical 0
channel O 0
macromolecular O 0
complex O 0
within O 0
the O 0
central O 0
nervous O 0
system O 0
to O 0
facilitate O 0
reflex O 0
bradycardia B-Disease 0
mediated O 0
through O 0
baroreceptor O 0
reflexes O 0
in O 0
response O 0
to O 0
an O 0
acute O 0
increase O 0
in O 0
arterial O 0
pressure O 0
. O 0

Initial O 0
potassium B-Chemical 0
loss O 0
and O 0
hypokalaemia B-Disease 0
during O 0
chlorthalidone B-Chemical 0
administration O 0
in O 0
patients O 0
with O 0
essential O 0
hypertension B-Disease 0
: O 0
the O 0
influence O 0
of O 0
dietary O 0
sodium B-Chemical 0
restriction O 0
. O 0

To O 0
investigate O 0
the O 0
initial O 0
potassium B-Chemical 0
loss O 0
and O 0
development O 0
of O 0
hypokalaemia B-Disease 0
during O 0
the O 0
administration O 0
of O 0
an O 0
oral O 0
diuretic O 0
, O 0
metabolic O 0
balance O 0
studies O 0
were O 0
performed O 0
in O 0
ten O 0
patients O 0
with O 0
essential O 0
hypertension B-Disease 0
who O 0
had O 0
shown O 0
hypokalaemia B-Disease 0
under O 0
prior O 0
oral O 0
diuretic O 0
treatment O 0
. O 0

Chlorthalidone B-Chemical 0
( O 0
50 O 0
mg O 0
daily O 0
) O 0
was O 0
given O 0
for O 0
14 O 0
days O 0
. O 0

Six O 0
patients O 0
received O 0
a O 0
normal O 0
- O 0
sodium B-Chemical 0
diet O 0
and O 0
four O 0
a O 0
low O 0
- O 0
sodium B-Chemical 0
( O 0
17 O 0
mmol O 0
/ O 0
day O 0
) O 0
diet O 0
. O 0

All O 0
patients O 0
had O 0
a O 0
normal O 0
initial O 0
total O 0
body O 0
potassium B-Chemical 0
( O 0
40K O 0
) O 0
. O 0

The O 0
electrolyte O 0
balances O 0
, O 0
weight O 0
, O 0
bromide O 0
space O 0
, O 0
plasma O 0
renin O 0
activity O 0
, O 0
and O 0
aldosterone B-Chemical 0
secretion O 0
rate O 0
were O 0
measured O 0
. O 0

In O 0
both O 0
groups O 0
a O 0
potassium B-Chemical 0
deficit O 0
developed O 0
, O 0
with O 0
proportionally O 0
larger O 0
losses O 0
from O 0
the O 0
extracellular O 0
than O 0
from O 0
the O 0
intracellular O 0
compartment O 0
. O 0

In O 0
the O 0
normal O 0
- O 0
sodium B-Chemical 0
group O 0
the O 0
highest O 0
mean O 0
potassium B-Chemical 0
deficit O 0
was O 0
176 O 0
mmol O 0
on O 0
day O 0
9 O 0
, O 0
after O 0
which O 0
some O 0
potassium B-Chemical 0
was O 0
regained O 0
; O 0
in O 0
the O 0
low O 0
- O 0
sodium B-Chemical 0
group O 0
the O 0
highest O 0
deficit O 0
was O 0
276 O 0
mmol O 0
on O 0
day O 0
13 O 0
. O 0

The O 0
normal O 0
- O 0
sodium B-Chemical 0
group O 0
showed O 0
an O 0
immediate O 0
but O 0
temporary O 0
rise O 0
of O 0
the O 0
renin O 0
and O 0
aldosterone B-Chemical 0
levels O 0
; O 0
in O 0
the O 0
low O 0
- O 0
sodium B-Chemical 0
group O 0
renin O 0
and O 0
aldosterone B-Chemical 0
increased O 0
more O 0
slowly O 0
but O 0
remained O 0
elevated O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
dietary O 0
sodium B-Chemical 0
restriction O 0
increases O 0
diuretic O 0
- O 0
induced O 0
potassium B-Chemical 0
loss O 0
, O 0
presumably O 0
by O 0
an O 0
increased O 0
activity O 0
of O 0
the O 0
renin O 0
- O 0
angiotensin B-Chemical 0
- O 0
aldosterone B-Chemical 0
system O 0
, O 0
while O 0
sodium B-Chemical 0
delivery O 0
to O 0
the O 0
distal O 0
renal O 0
tubules O 0
remains O 0
sufficiently O 0
high O 0
to O 0
allow O 0
increased O 0
potassium B-Chemical 0
secretion O 0
. O 0

Reversal O 0
of O 0
neuroleptic O 0
- O 0
induced O 0
catalepsy B-Disease 0
by O 0
novel O 0
aryl B-Chemical 0
- I-Chemical 0
piperazine I-Chemical 0
anxiolytic O 0
drugs O 0
. O 0

The O 0
novel O 0
anxiolytic O 0
drug O 0
, O 0
buspirone B-Chemical 0
, O 0
reverses O 0
catalepsy B-Disease 0
induced O 0
by O 0
haloperidol B-Chemical 0
. O 0

A O 0
series O 0
of O 0
aryl B-Chemical 0
- I-Chemical 0
piperazine I-Chemical 0
analogues O 0
of O 0
buspirone B-Chemical 0
and O 0
other O 0
5 B-Chemical 0
- I-Chemical 0
hydroxytryptaminergic I-Chemical 0
agonists I-Chemical 0
were O 0
tested O 0
for O 0
their O 0
ability O 0
to O 0
reverse O 0
haloperidol B-Chemical 0
induced O 0
catalepsy B-Disease 0
. O 0

Those O 0
drugs O 0
with O 0
strong O 0
affinity O 0
for O 0
5 B-Chemical 0
- I-Chemical 0
hydroxytryptamine1a I-Chemical 0
receptors O 0
were O 0
able O 0
to O 0
reverse O 0
catalepsy B-Disease 0
. O 0

Drugs O 0
with O 0
affinity O 0
for O 0
other O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
receptors O 0
or O 0
weak O 0
affinity O 0
were O 0
ineffective O 0
. O 0

However O 0
, O 0
inhibition O 0
of O 0
postsynaptic O 0
5 B-Chemical 0
- I-Chemical 0
HT I-Chemical 0
receptors O 0
neither O 0
inhibited O 0
nor O 0
potentiated O 0
reversal O 0
of O 0
catalepsy B-Disease 0
and O 0
leaves O 0
open O 0
the O 0
question O 0
as O 0
to O 0
the O 0
site O 0
or O 0
mechanism O 0
for O 0
this O 0
effect O 0
. O 0

Glycopyrronium B-Chemical 0
requirements O 0
for O 0
antagonism O 0
of O 0
the O 0
muscarinic O 0
side O 0
effects O 0
of O 0
edrophonium B-Chemical 0
. O 0

We O 0
have O 0
compared O 0
, O 0
in O 0
60 O 0
adult O 0
patients O 0
, O 0
the O 0
cardiovascular O 0
effects O 0
of O 0
glycopyrronium B-Chemical 0
5 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
and O 0
10 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
given O 0
either O 0
simultaneously O 0
or O 0
1 O 0
min O 0
before O 0
edrophonium B-Chemical 0
1 O 0
mg O 0
kg O 0
- O 0
1 O 0
. O 0

Significant O 0
differences O 0
between O 0
the O 0
four O 0
groups O 0
were O 0
detected 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

Both O 0
groups O 0
receiving O 0
10 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
showed O 0
increases O 0
in O 0
heart O 0
rate O 0
of O 0
up O 0
to O 0
30 O 0
beat O 0
min O 0
- O 0
1 O 0
( O 0
95 O 0
% O 0
confidence O 0
limits O 0
28 O 0
- O 0
32 O 0
beat O 0
min O 0
- O 0
1 O 0
) O 0
. O 0

Use O 0
of O 0
glycopyrronium B-Chemical 0
5 O 0
micrograms O 0
kg O 0
- O 0
1 O 0
provided O 0
greater O 0
cardiovascular O 0
stability O 0
and O 0
, O 0
given O 0
1 O 0
min O 0
before O 0
the O 0
edrophonium B-Chemical 0
, O 0
was O 0
sufficient O 0
to O 0
minimize O 0
early O 0
, O 0
edrophonium B-Chemical 0
- O 0
induced O 0
bradycardias B-Disease 0
. O 0

This O 0
low O 0
dose O 0
of O 0
glycopyrronium B-Chemical 0
provided O 0
good O 0
control O 0
of O 0
oropharyngeal O 0
secretions O 0
. O 0

Selective O 0
injection O 0
of O 0
iopentol B-Chemical 0
, O 0
iohexol B-Chemical 0
and O 0
metrizoate B-Chemical 0
into O 0
the O 0
left O 0
coronary O 0
artery O 0
of O 0
the O 0
dog O 0
. O 0

Induction O 0
of O 0
ventricular B-Disease 0
fibrillation I-Disease 0
and O 0
decrease O 0
of O 0
aortic O 0
pressure O 0
. O 0

In O 0
twenty O 0
beagle O 0
dogs O 0
selective O 0
injections O 0
were O 0
made O 0
into O 0
the O 0
left O 0
coronary O 0
artery O 0
with O 0
iopentol B-Chemical 0
, O 0
iohexol B-Chemical 0
and O 0
metrizoate B-Chemical 0
in O 0
doses O 0
of O 0
4 O 0
ml O 0
, O 0
8 O 0
ml O 0
and O 0
16 O 0
ml O 0
. O 0

Thirty O 0
- O 0
six O 0
iopentol B-Chemical 0
injections O 0
, O 0
35 O 0
iohexol B-Chemical 0
injections O 0
and O 0
37 O 0
metrizoate B-Chemical 0
injections O 0
were O 0
made O 0
. O 0

Frequencies O 0
of O 0
ventricular B-Disease 0
fibrillation I-Disease 0
were O 0
significantly O 0
lower O 0
( O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
05 O 0
) O 0
after O 0
iopentol B-Chemical 0
( O 0
0 O 0
% O 0
) O 0
and O 0
iohexol B-Chemical 0
( O 0
3 O 0
% O 0
) O 0
than O 0
after O 0
metrizoate B-Chemical 0
( O 0
22 O 0
% O 0
) O 0
. O 0

Iopentol B-Chemical 0
and O 0
iohexol B-Chemical 0
also O 0
produced O 0
significantly O 0
less O 0
decrease O 0
in O 0
aortic O 0
blood O 0
pressure O 0
than O 0
metrizoate B-Chemical 0
at O 0
the O 0
different O 0
doses O 0
. O 0

Thyroid O 0
function O 0
and O 0
urine O 0
- O 0
concentrating O 0
ability O 0
during O 0
lithium B-Chemical 0
treatment O 0
. O 0

It O 0
has O 0
been O 0
suggested O 0
that O 0
adenylate O 0
cyclase O 0
inhibition O 0
may O 0
be O 0
important O 0
in O 0
the O 0
development O 0
of O 0
both O 0
nephrogenic B-Disease 0
diabetes I-Disease 0
insipidus I-Disease 0
and O 0
hypothyroidism B-Disease 0
during O 0
lithium B-Chemical 0
treatment O 0
. O 0

We O 0
measured O 0
serum O 0
thyroxine B-Chemical 0
and O 0
urine O 0
- O 0
concentrating O 0
ability O 0
( O 0
Umax O 0
) O 0
in O 0
response O 0
to O 0
desmopressin O 0
( O 0
DDAVP O 0
) O 0
in O 0
85 O 0
patients O 0
receiving O 0
lithium B-Chemical 0
. O 0

Hypothyroidism B-Disease 0
developed O 0
in O 0
eight O 0
patients O 0
while O 0
they O 0
were O 0
taking O 0
lithium B-Chemical 0
. O 0

Impaired O 0
Umax O 0
was O 0
found O 0
in O 0
both O 0
euthyroid O 0
and O 0
hypothyroid B-Disease 0
patients O 0
while O 0
some O 0
hypothyroid B-Disease 0
patients O 0
concentrated O 0
their O 0
urine O 0
well O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
the O 0
dominant O 0
mechanisms O 0
by O 0
which O 0
lithium B-Chemical 0
exerts O 0
these O 0
two O 0
effects O 0
are O 0
different O 0
. O 0

Remodelling O 0
of O 0
nerve O 0
structure O 0
in O 0
experimental O 0
isoniazid B-Chemical 0
neuropathy B-Disease 0
in O 0
the O 0
rat O 0
. O 0

The O 0
neuropathy B-Disease 0
caused O 0
by O 0
a O 0
single O 0
dose O 0
of O 0
isoniazid B-Chemical 0
in O 0
rats O 0
was O 0
studied O 0
with O 0
a O 0
computer O 0
- O 0
assisted O 0
morphometric O 0
method O 0
. O 0

Scatter O 0
diagrams O 0
of O 0
the O 0
g O 0
ratio O 0
( O 0
quotient O 0
fibre O 0
diameter O 0
/ O 0
axon O 0
diameter O 0
) O 0
define O 0
regenerating O 0
fibres O 0
as O 0
a O 0
distinct O 0
population O 0
, O 0
distinguishable O 0
from O 0
the O 0
surviving O 0
fibres O 0
by O 0
reduced O 0
sheath O 0
thickness O 0
and O 0
reduced O 0
axon O 0
calibre O 0
. O 0

There O 0
was O 0
also O 0
evidence O 0
of O 0
a O 0
subtle O 0
direct O 0
toxic O 0
effect O 0
on O 0
the O 0
entire O 0
fibre O 0
population O 0
, O 0
causing O 0
axon O 0
shrinkage O 0
masked O 0
by O 0
readjustment O 0
of O 0
the O 0
myelin O 0
sheath O 0
. O 0

Multicenter O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
multiple O 0
- O 0
dose O 0
, O 0
parallel O 0
- O 0
groups O 0
efficacy O 0
and O 0
safety O 0
trial O 0
of O 0
azelastine B-Chemical 0
, O 0
chlorpheniramine B-Chemical 0
, O 0
and O 0
placebo O 0
in O 0
the O 0
treatment O 0
of O 0
spring B-Disease 0
allergic I-Disease 0
rhinitis I-Disease 0
. O 0

Azelastine B-Chemical 0
, O 0
a O 0
novel O 0
antiallergic O 0
medication O 0
, O 0
was O 0
compared O 0
with O 0
chlorpheniramine B-Chemical 0
maleate I-Chemical 0
and O 0
placebo O 0
for O 0
efficacy O 0
and O 0
safety O 0
in O 0
the O 0
treatment O 0
of O 0
spring B-Disease 0
allergic I-Disease 0
rhinitis I-Disease 0
in O 0
a O 0
multicenter O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
multiple O 0
- O 0
dose O 0
, O 0
parallel O 0
- O 0
groups O 0
study O 0
. O 0

One O 0
hundred O 0
fifty O 0
- O 0
five O 0
subjects O 0
participated O 0
. O 0

Subjects O 0
ranged O 0
in O 0
age O 0
from O 0
18 O 0
to O 0
60 O 0
years O 0
of O 0
age O 0
and O 0
had O 0
at O 0
least O 0
a O 0
2 O 0
- O 0
year O 0
history O 0
of O 0
spring B-Disease 0
allergic I-Disease 0
rhinitis I-Disease 0
, O 0
confirmed O 0
by O 0
positive O 0
skin O 0
test O 0
to O 0
spring O 0
aeroallergens O 0
. O 0

Medications O 0
were O 0
given O 0
four O 0
times O 0
daily O 0
; O 0
the O 0
azelastine B-Chemical 0
groups O 0
received O 0
0 O 0
. O 0
5 O 0
, O 0
1 O 0
. O 0
0 O 0
, O 0
or O 0
2 O 0
. O 0
0 O 0
mg O 0
in O 0
the O 0
morning O 0
and O 0
evening O 0
with O 0
placebo O 0
in O 0
the O 0
early O 0
and O 0
late O 0
afternoon O 0
; O 0
the O 0
chlorpheniramine B-Chemical 0
group O 0
received O 0
4 O 0
. O 0
0 O 0
mg O 0
four O 0
times O 0
daily O 0
. O 0

Daily O 0
subject O 0
symptom O 0
cards O 0
were O 0
completed O 0
during O 0
a O 0
screening O 0
period O 0
to O 0
assess O 0
pretreatment O 0
symptoms O 0
and O 0
during O 0
a O 0
4 O 0
- O 0
week O 0
treatment O 0
period O 0
while O 0
subjects O 0
received O 0
study O 0
medications O 0
. O 0

Individual O 0
symptoms O 0
, O 0
total O 0
symptoms O 0
, O 0
and O 0
major O 0
symptoms O 0
were O 0
compared O 0
to O 0
determine O 0
efficacy O 0
of O 0
medication O 0
. O 0

Elicited O 0
, O 0
volunteered O 0
, O 0
and O 0
observed O 0
adverse O 0
experiences O 0
were O 0
recorded O 0
for O 0
each O 0
subject O 0
and O 0
compared O 0
among O 0
groups O 0
. O 0

Vital O 0
signs O 0
, O 0
body O 0
weights O 0
, O 0
serum O 0
chemistry O 0
values O 0
, O 0
complete O 0
blood O 0
cell O 0
counts O 0
, O 0
urine O 0
studies O 0
, O 0
and O 0
electrocardiograms O 0
were O 0
obtained O 0
for O 0
each O 0
subject O 0
and O 0
compared O 0
among O 0
groups O 0
. O 0

Symptoms O 0
relief O 0
in O 0
the O 0
group O 0
receiving O 0
the O 0
highest O 0
concentration O 0
of O 0
azelastine B-Chemical 0
( O 0
2 O 0
. O 0
0 O 0
mg O 0
twice O 0
daily O 0
) O 0
was O 0
statistically O 0
greater O 0
than O 0
in O 0
the O 0
placebo O 0
group O 0
during O 0
all O 0
weeks O 0
of O 0
the O 0
study O 0
. O 0

Lower O 0
doses O 0
of O 0
azelastine B-Chemical 0
were O 0
statistically O 0
more O 0
effective O 0
than O 0
placebo O 0
only O 0
during O 0
portions O 0
of O 0
the O 0
first O 0
3 O 0
weeks O 0
of O 0
the O 0
study O 0
. O 0

In O 0
contrast O 0
, O 0
although O 0
the O 0
chlorpheniramine B-Chemical 0
group O 0
did O 0
have O 0
fewer O 0
symptoms O 0
than O 0
the O 0
placebo O 0
group O 0
during O 0
the O 0
study O 0
, O 0
the O 0
difference O 0
never O 0
reached O 0
statistical O 0
significance O 0
during O 0
any O 0
week O 0
of O 0
the O 0
study O 0
. O 0

There O 0
were O 0
no O 0
serious O 0
side O 0
effects O 0
in O 0
any O 0
of O 0
the O 0
treatment O 0
groups O 0
. O 0

Drowsiness B-Disease 0
and O 0
altered B-Disease 0
taste I-Disease 0
perception I-Disease 0
were O 0
increased O 0
significantly O 0
over O 0
placebo O 0
only O 0
in O 0
the O 0
high O 0
- O 0
dose O 0
azelastine B-Chemical 0
group O 0
. O 0

Azelastine B-Chemical 0
appears O 0
to O 0
be O 0
a O 0
safe O 0
, O 0
efficacious O 0
medication O 0
for O 0
seasonal B-Disease 0
allergic I-Disease 0
rhinitis I-Disease 0
. O 0

Toxicity B-Disease 0
due O 0
to O 0
remission O 0
inducing O 0
drugs O 0
in O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
. O 0

Association O 0
with O 0
HLA O 0
- O 0
B35 O 0
and O 0
Cw4 O 0
antigens O 0
. O 0

Twenty O 0
- O 0
five O 0
patients O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
( O 0
RA B-Disease 0
) O 0
who O 0
developed O 0
toxicity B-Disease 0
while O 0
taking O 0
remission O 0
inducing O 0
drugs O 0
and O 0
30 O 0
without O 0
toxicity B-Disease 0
were O 0
studied O 0
for O 0
possible O 0
associations O 0
with O 0
class O 0
I O 0
and O 0
II O 0
HLA O 0
antigens O 0
. O 0

A O 0
strong O 0
association O 0
has O 0
been O 0
found O 0
between O 0
nephritis B-Disease 0
and O 0
dermatitis B-Disease 0
due O 0
to O 0
Tiopronin B-Chemical 0
( O 0
a O 0
D B-Chemical 0
- I-Chemical 0
Penicillamine I-Chemical 0
like O 0
compound O 0
) O 0
and O 0
class O 0
I O 0
antigens O 0
B35 O 0
- O 0
Cw4 O 0
, O 0
and O 0
between O 0
dermatitis B-Disease 0
due O 0
to O 0
gold B-Chemical 0
thiosulphate B-Chemical 0
and O 0
B35 O 0
. O 0

Compared O 0
to O 0
healthy O 0
controls O 0
a O 0
lower O 0
DR5 O 0
frequency O 0
was O 0
observed O 0
in O 0
patients O 0
with O 0
RA B-Disease 0
except O 0
for O 0
the O 0
Tiopronin B-Chemical 0
related O 0
nephritis B-Disease 0
group O 0
. O 0

Transient O 0
contralateral B-Disease 0
rotation I-Disease 0
following O 0
unilateral O 0
substantia B-Disease 0
nigra I-Disease 0
lesion I-Disease 0
reflects O 0
susceptibility O 0
of O 0
the O 0
nigrostriatal O 0
system O 0
to O 0
exhaustion O 0
by O 0
amphetamine B-Chemical 0
. O 0

Following O 0
unilateral O 0
6 B-Chemical 0
- I-Chemical 0
OHDA I-Chemical 0
induced O 0
SN B-Disease 0
lesion I-Disease 0
, O 0
a O 0
transient O 0
period O 0
of O 0
contralateral B-Disease 0
rotation I-Disease 0
has O 0
been O 0
reported O 0
to O 0
precede O 0
the O 0
predominant O 0
ipsilateral B-Disease 0
circling I-Disease 0
. O 0

In O 0
order O 0
to O 0
clarify O 0
the O 0
nature O 0
of O 0
this O 0
initial O 0
contralateral B-Disease 0
rotation I-Disease 0
we O 0
examined O 0
the O 0
effect O 0
of O 0
the O 0
duration O 0
of O 0
recovery O 0
period O 0
after O 0
the O 0
lesion O 0
, O 0
on O 0
amphetamine B-Chemical 0
- O 0
induced O 0
rotational B-Disease 0
behavior I-Disease 0
. O 0

Three O 0
days O 0
post O 0
lesion O 0
, O 0
most O 0
rats O 0
circled O 0
predominantly O 0
contralaterally O 0
to O 0
the O 0
lesion O 0
. O 0

Such O 0
contralateral B-Disease 0
rotation I-Disease 0
may O 0
result O 0
from O 0
either O 0
degeneration O 0
- O 0
induced O 0
breakdown O 0
of O 0
the O 0
DA O 0
pool O 0
, O 0
or O 0
lesion O 0
- O 0
induced O 0
increase O 0
of O 0
DA O 0
turnover O 0
in O 0
the O 0
spared O 0
neurons O 0
. O 0

A O 0
substantial O 0
degree O 0
of O 0
contralateral O 0
preference O 0
was O 0
still O 0
evident O 0
when O 0
amphetamine B-Chemical 0
was O 0
administered O 0
for O 0
the O 0
first O 0
time O 0
24 O 0
days O 0
after O 0
lesioning O 0
, O 0
indicating O 0
involvement O 0
of O 0
spared O 0
cells O 0
in O 0
the O 0
contralateral B-Disease 0
rotation I-Disease 0
. O 0

However O 0
, O 0
regardless O 0
of O 0
the O 0
duration O 0
of O 0
recovery O 0
( O 0
and O 0
irrespective O 0
of O 0
either O 0
lesion O 0
volume O 0
, O 0
amphetamine B-Chemical 0
dose O 0
, O 0
or O 0
post O 0
- O 0
lesion O 0
motor O 0
exercise O 0
) O 0
, O 0
amphetamine B-Chemical 0
- O 0
induced O 0
rotation B-Disease 0
tended O 0
to O 0
become O 0
gradually O 0
more O 0
ipsilateral O 0
as O 0
the O 0
observation O 0
session O 0
progressed O 0
, O 0
and O 0
all O 0
rats O 0
circled O 0
ipsilaterally O 0
to O 0
the O 0
lesion O 0
in O 0
response O 0
to O 0
further O 0
amphetamine B-Chemical 0
injections O 0
. O 0

These O 0
findings O 0
suggest O 0
that O 0
amphetamine B-Chemical 0
has O 0
an O 0
irreversible O 0
effect O 0
on O 0
the O 0
post O 0
- O 0
lesion O 0
DA O 0
pool O 0
contributing O 0
to O 0
contralateral B-Disease 0
rotation I-Disease 0
. O 0

Mitomycin B-Chemical 0
C I-Chemical 0
associated O 0
hemolytic B-Disease 0
uremic I-Disease 0
syndrome I-Disease 0
. O 0

Mitomycin B-Chemical 0
C I-Chemical 0
associated O 0
Hemolytic B-Disease 0
Uremic I-Disease 0
Syndrome I-Disease 0
( O 0
HUS B-Disease 0
) O 0
is O 0
a O 0
potentially O 0
fatal O 0
but O 0
uncommon O 0
condition O 0
that O 0
is O 0
not O 0
yet O 0
widely O 0
recognised O 0
. O 0

It O 0
consists O 0
of O 0
microangiopathic O 0
hemolytic B-Disease 0
anemia I-Disease 0
, O 0
thrombocytopenia B-Disease 0
and O 0
progressive O 0
renal B-Disease 0
failure I-Disease 0
associated O 0
with O 0
mitomycin B-Chemical 0
C I-Chemical 0
treatment O 0
and O 0
affects O 0
about O 0
10 O 0
% O 0
of O 0
patients O 0
treated O 0
with O 0
this O 0
agent O 0
. O 0

The O 0
renal B-Disease 0
failure I-Disease 0
usually O 0
develops O 0
about O 0
8 O 0
- O 0
10 O 0
mth O 0
after O 0
start O 0
of O 0
mitomycin B-Chemical 0
C I-Chemical 0
treatment O 0
and O 0
the O 0
mortality O 0
is O 0
approximately O 0
60 O 0
% O 0
from O 0
renal B-Disease 0
failure I-Disease 0
or O 0
pulmonary B-Disease 0
edema I-Disease 0
. O 0

Renal B-Disease 0
lesions I-Disease 0
are O 0
similar O 0
to O 0
those O 0
seen O 0
in O 0
idiopathic O 0
HUS B-Disease 0
and O 0
include O 0
arteriolar O 0
fibrin O 0
thrombi B-Disease 0
, O 0
expanded O 0
subendothelial O 0
zones O 0
in O 0
glomerular O 0
capillary O 0
walls O 0
, O 0
ischemic B-Disease 0
wrinkling O 0
of O 0
glomerular O 0
basement O 0
membranes O 0
and O 0
mesangiolysis O 0
. O 0

The O 0
mechanism O 0
of O 0
action O 0
is O 0
postulated O 0
as O 0
mitomycin B-Chemical 0
C I-Chemical 0
- O 0
induced O 0
endothelial O 0
cell O 0
damage O 0
. O 0

We O 0
describe O 0
the O 0
clinical O 0
course O 0
and O 0
pathological O 0
findings O 0
in O 0
a O 0
65 O 0
yr O 0
- O 0
old O 0
man O 0
with O 0
gastric B-Disease 0
adenocarcinoma I-Disease 0
who O 0
developed O 0
renal B-Disease 0
failure I-Disease 0
and O 0
thrombocytopenia B-Disease 0
while O 0
on O 0
treatment O 0
with O 0
mitomycin B-Chemical 0
C I-Chemical 0
and O 0
died O 0
in O 0
pulmonary B-Disease 0
edema I-Disease 0
. O 0

Ketanserin B-Chemical 0
pretreatment O 0
reverses O 0
alfentanil B-Chemical 0
- O 0
induced O 0
muscle B-Disease 0
rigidity I-Disease 0
. O 0

Systemic O 0
pretreatment O 0
with O 0
ketanserin B-Chemical 0
, O 0
a O 0
relatively O 0
specific O 0
type O 0
- O 0
2 O 0
serotonin B-Chemical 0
receptor O 0
antagonist O 0
, O 0
significantly O 0
attenuated O 0
the O 0
muscle B-Disease 0
rigidity I-Disease 0
produced O 0
in O 0
rats O 0
by O 0
the O 0
potent O 0
short O 0
- O 0
acting O 0
opiate O 0
agonist O 0
alfentanil B-Chemical 0
. O 0

Following O 0
placement O 0
of O 0
subcutaneous O 0
electrodes O 0
in O 0
each O 0
animal O 0
' O 0
s O 0
left O 0
gastrocnemius O 0
muscle O 0
, O 0
rigidity B-Disease 0
was O 0
assessed O 0
by O 0
analyzing O 0
root O 0
- O 0
mean O 0
- O 0
square O 0
electromyographic O 0
activity O 0
. O 0

Intraperitoneal O 0
ketanserin B-Chemical 0
administration O 0
at O 0
doses O 0
of O 0
0 O 0
. O 0
63 O 0
and O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
prevented O 0
the O 0
alfentanil B-Chemical 0
- O 0
induced O 0
increase O 0
in O 0
electromyographic O 0
activity O 0
compared O 0
with O 0
animals O 0
pretreated O 0
with O 0
saline O 0
. O 0

Chlordiazepoxide B-Chemical 0
at O 0
doses O 0
up O 0
to O 0
10 O 0
mg O 0
/ O 0
kg O 0
failed O 0
to O 0
significantly O 0
influence O 0
the O 0
rigidity B-Disease 0
produced O 0
by O 0
alfentanil B-Chemical 0
. O 0

Despite O 0
the O 0
absence O 0
of O 0
rigidity B-Disease 0
, O 0
animals O 0
that O 0
received O 0
ketanserin B-Chemical 0
( O 0
greater O 0
than O 0
0 O 0
. O 0
31 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
followed O 0
by O 0
alfentanil B-Chemical 0
were O 0
motionless O 0
, O 0
flaccid O 0
, O 0
and O 0
less O 0
responsive O 0
to O 0
external O 0
stimuli O 0
than O 0
were O 0
animals O 0
receiving O 0
alfentanil B-Chemical 0
alone O 0
. O 0

Rats O 0
that O 0
received O 0
ketanserin B-Chemical 0
and O 0
alfentanil B-Chemical 0
exhibited O 0
less O 0
rearing O 0
and O 0
exploratory O 0
behavior O 0
at O 0
the O 0
end O 0
of O 0
the O 0
60 O 0
- O 0
min O 0
recording O 0
period O 0
than O 0
did O 0
animals O 0
that O 0
received O 0
ketanserin B-Chemical 0
alone O 0
. O 0

These O 0
results O 0
, O 0
in O 0
combination O 0
with O 0
previous O 0
work O 0
, O 0
suggest O 0
that O 0
muscle B-Disease 0
rigidity I-Disease 0
, O 0
a O 0
clinically O 0
relevant O 0
side O 0
- O 0
effect O 0
of O 0
parenteral O 0
narcotic O 0
administration O 0
, O 0
may O 0
be O 0
partly O 0
mediated O 0
via O 0
serotonergic O 0
pathways O 0
. O 0

Pretreatment O 0
with O 0
type O 0
- O 0
2 O 0
serotonin B-Chemical 0
antagonists O 0
may O 0
be O 0
clinically O 0
useful O 0
in O 0
attenuating O 0
opiate O 0
- O 0
induced O 0
rigidity B-Disease 0
, O 0
although O 0
further O 0
studies O 0
will O 0
be O 0
necessary O 0
to O 0
assess O 0
the O 0
interaction O 0
of O 0
possibly O 0
enhanced O 0
CNS O 0
, O 0
cardiovascular B-Disease 0
, I-Disease 0
and I-Disease 0
respiratory I-Disease 0
depression I-Disease 0
. O 0

Antagonism O 0
of O 0
diazepam B-Chemical 0
- O 0
induced O 0
sedative O 0
effects O 0
by O 0
Ro15 B-Chemical 0
- I-Chemical 0
1788 I-Chemical 0
in O 0
patients O 0
after O 0
surgery O 0
under O 0
lumbar O 0
epidural O 0
block O 0
. O 0

A O 0
double O 0
- O 0
blind O 0
placebo O 0
- O 0
controlled O 0
investigation O 0
of O 0
efficacy O 0
and O 0
safety 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
assess O 0
the O 0
efficacy O 0
of O 0
Ro15 B-Chemical 0
- I-Chemical 0
1788 I-Chemical 0
and O 0
a O 0
placebo O 0
in O 0
reversing O 0
diazepam B-Chemical 0
- O 0
induced O 0
effects O 0
after O 0
surgery O 0
under O 0
epidural O 0
block O 0
, O 0
and O 0
to O 0
evaluate O 0
the O 0
local O 0
tolerance O 0
and O 0
general O 0
safety O 0
of O 0
Ro15 B-Chemical 0
- I-Chemical 0
1788 I-Chemical 0
. O 0

Fifty O 0
- O 0
seven O 0
patients O 0
were O 0
sedated O 0
with O 0
diazepam B-Chemical 0
for O 0
surgery O 0
under O 0
epidural O 0
anaesthesia O 0
. O 0

Antagonism O 0
of O 0
diazepam B-Chemical 0
- O 0
induced O 0
effects O 0
by O 0
Ro15 B-Chemical 0
- I-Chemical 0
1788 I-Chemical 0
was O 0
investigated O 0
postoperatively O 0
in O 0
a O 0
double O 0
- O 0
blind O 0
placebo O 0
- O 0
controlled O 0
trial O 0
. O 0

The O 0
patient O 0
' O 0
s O 0
subjective O 0
assessment O 0
of O 0
mood O 0
rating O 0
, O 0
an O 0
objective O 0
test O 0
of O 0
performance O 0
, O 0
a O 0
test O 0
for O 0
amnesia B-Disease 0
, O 0
and O 0
vital O 0
signs O 0
were O 0
recorded O 0
for O 0
up O 0
to O 0
300 O 0
min O 0
after O 0
administration O 0
of O 0
the O 0
trial O 0
drug O 0
. O 0

No O 0
significant O 0
differences O 0
between O 0
the O 0
two O 0
groups O 0
were O 0
observed O 0
for O 0
mood O 0
rating O 0
, O 0
amnesia B-Disease 0
, O 0
or O 0
vital O 0
signs O 0
. O 0

The O 0
Ro15 B-Chemical 0
- I-Chemical 0
1788 I-Chemical 0
group O 0
showed O 0
a O 0
significant O 0
improvement O 0
in O 0
the O 0
performance O 0
test O 0
up O 0
to O 0
120 O 0
min O 0
after O 0
administration O 0
of O 0
the O 0
drug O 0
. O 0

There O 0
was O 0
no O 0
evidence O 0
of O 0
reaction O 0
at O 0
the O 0
injection O 0
site O 0
. O 0

Chorea B-Disease 0
associated O 0
with O 0
oral B-Chemical 0
contraception I-Chemical 0
. O 0

Three O 0
patients O 0
developed O 0
chorea B-Disease 0
while O 0
receiving O 0
oral B-Chemical 0
contraceptives I-Chemical 0
. O 0

Two O 0
were O 0
young O 0
patients O 0
whose O 0
chorea B-Disease 0
developed O 0
long O 0
after O 0
treatment O 0
had O 0
been O 0
started O 0
and O 0
disappeared O 0
soon O 0
after O 0
it O 0
had O 0
been O 0
discontinued O 0
. O 0

The O 0
third O 0
patient O 0
had O 0
acute O 0
amphetamine B-Chemical 0
- O 0
induced O 0
chorea B-Disease 0
after O 0
prolonged O 0
oral B-Chemical 0
contraception I-Chemical 0
. O 0

Prolonged O 0
administration O 0
of O 0
female O 0
sex O 0
hormones O 0
is O 0
a O 0
possible O 0
cause O 0
of O 0
chorea B-Disease 0
in O 0
women O 0
who O 0
have O 0
not O 0
previously O 0
had O 0
chorea B-Disease 0
or O 0
rheumatic B-Disease 0
fever I-Disease 0
. O 0

Co O 0
- O 0
carcinogenic B-Disease 0
effect O 0
of O 0
retinyl B-Chemical 0
acetate I-Chemical 0
on O 0
forestomach B-Disease 0
carcinogenesis I-Disease 0
of O 0
male O 0
F344 O 0
rats O 0
induced O 0
with O 0
butylated B-Chemical 0
hydroxyanisole I-Chemical 0
. O 0

The O 0
potential O 0
modifying O 0
effect O 0
of O 0
retinyl B-Chemical 0
acetate I-Chemical 0
( O 0
RA B-Chemical 0
) O 0
on O 0
butylated B-Chemical 0
hydroxyanisole I-Chemical 0
( O 0
BHA B-Chemical 0
) O 0
- O 0
induced O 0
rat O 0
forestomach B-Disease 0
tumorigenesis I-Disease 0
was O 0
examined O 0
. O 0

Male O 0
F344 O 0
rats O 0
, O 0
5 O 0
weeks O 0
of O 0
age O 0
, O 0
were O 0
maintained O 0
on O 0
diet O 0
containing O 0
1 O 0
% O 0
or O 0
2 O 0
% O 0
BHA B-Chemical 0
by O 0
weight O 0
and O 0
simultaneously O 0
on O 0
drinking O 0
water O 0
supplemented O 0
with O 0
RA B-Chemical 0
at O 0
various O 0
concentrations O 0
( O 0
w O 0
/ O 0
v O 0
) O 0
for O 0
52 O 0
weeks O 0
. O 0

In O 0
groups O 0
given O 0
2 O 0
% O 0
BHA B-Chemical 0
, O 0
although O 0
marked O 0
hyperplastic O 0
changes O 0
of O 0
the O 0
forestomach O 0
epithelium O 0
were O 0
observed O 0
in O 0
all O 0
animals O 0
, O 0
co O 0
- O 0
administration O 0
of O 0
0 O 0
. O 0
25 O 0
% O 0
RA B-Chemical 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
increased O 0
the O 0
incidence O 0
of O 0
forestomach B-Disease 0
tumors I-Disease 0
( O 0
squamous B-Disease 0
cell I-Disease 0
papilloma I-Disease 0
and O 0
carcinoma B-Disease 0
) O 0
to O 0
60 O 0
% O 0
( O 0
9 O 0
/ O 0
15 O 0
, O 0
2 O 0
rats O 0
with O 0
carcinoma B-Disease 0
) O 0
from O 0
15 O 0
% O 0
( O 0
3 O 0
/ O 0
20 O 0
, O 0
one O 0
rat O 0
with O 0
carcinoma B-Disease 0
) O 0
in O 0
the O 0
group O 0
given O 0
RA B-Chemical 0
- O 0
free O 0
water O 0
. O 0

In O 0
rats O 0
given O 0
1 O 0
% O 0
BHA B-Chemical 0
, O 0
RA B-Chemical 0
co O 0
- O 0
administered O 0
at O 0
a O 0
dose O 0
of O 0
0 O 0
. O 0
05 O 0
, O 0
0 O 0
. O 0
1 O 0
, O 0
0 O 0
. O 0
2 O 0
or O 0
0 O 0
. O 0
25 O 0
% O 0
showed O 0
a O 0
dose O 0
- O 0
dependent O 0
enhancing O 0
effect O 0
on O 0
the O 0
development O 0
of O 0
the O 0
BHA B-Chemical 0
- O 0
induced O 0
epithelial B-Disease 0
hyperplasia I-Disease 0
. O 0

Tumors B-Disease 0
, O 0
all O 0
papillomas B-Disease 0
, O 0
were O 0
induced O 0
in O 0
3 O 0
rats O 0
( O 0
17 O 0
% O 0
) O 0
with O 0
0 O 0
. O 0
25 O 0
% O 0
RA B-Chemical 0
and O 0
in O 0
one O 0
rat O 0
( O 0
10 O 0
% O 0
) O 0
with O 0
0 O 0
. O 0
05 O 0
% O 0
RA B-Chemical 0
co O 0
- O 0
administration O 0
. O 0

RA B-Chemical 0
alone O 0
did O 0
not O 0
induce O 0
hyperplastic O 0
changes O 0
in O 0
the O 0
forestomach O 0
. O 0

These O 0
findings O 0
indicate O 0
that O 0
RA B-Chemical 0
acted O 0
as O 0
a O 0
co O 0
- O 0
carcinogen O 0
in O 0
the O 0
BHA B-Chemical 0
forestomach B-Disease 0
carcinogenesis I-Disease 0
of O 0
the O 0
rat O 0
. O 0

A O 0
prospective O 0
study O 0
on O 0
the O 0
dose O 0
dependency O 0
of O 0
cardiotoxicity B-Disease 0
induced O 0
by O 0
mitomycin B-Chemical 0
C I-Chemical 0
. O 0

Since O 0
1975 O 0
mitomycin B-Chemical 0
C I-Chemical 0
( O 0
MMC B-Chemical 0
) O 0
has O 0
been O 0
suggested O 0
to O 0
be O 0
cardiotoxic B-Disease 0
, O 0
especially O 0
when O 0
combined O 0
with O 0
or O 0
given O 0
following O 0
doxorubicin B-Chemical 0
. O 0

Data O 0
on O 0
dose O 0
dependency O 0
or O 0
incidence O 0
concerning O 0
this O 0
side O 0
effect O 0
were O 0
not O 0
known O 0
. O 0

We O 0
have O 0
initiated O 0
a O 0
prospective O 0
study O 0
to O 0
obtain O 0
some O 0
more O 0
data O 0
on O 0
these O 0
subjects O 0
. O 0

Forty O 0
- O 0
four O 0
MMC B-Chemical 0
- O 0
treated O 0
patients O 0
were O 0
studied O 0
, O 0
37 O 0
of O 0
them O 0
could O 0
be O 0
evaluated O 0
. O 0

All O 0
patients O 0
were O 0
studied O 0
by O 0
repeated O 0
physical O 0
examinations O 0
, O 0
chest O 0
X O 0
- O 0
rays O 0
, O 0
electro O 0
- O 0
and O 0
echocardiography O 0
and O 0
radionuclide O 0
left O 0
ventricular O 0
ejection O 0
fraction O 0
( O 0
EF O 0
) O 0
determinations O 0
. O 0

The O 0
results O 0
were O 0
evaluated O 0
per O 0
cumulative O 0
dose O 0
level O 0
. O 0

One O 0
of O 0
the O 0
patients O 0
developed O 0
cardiac B-Disease 0
failure I-Disease 0
after O 0
30 O 0
mg O 0
m O 0
- O 0
2 O 0
MMC B-Chemical 0
and O 0
only O 0
150 O 0
mg O 0
m O 0
- O 0
2 O 0
doxorubicin B-Chemical 0
. O 0

The O 0
cardiac B-Disease 0
failure I-Disease 0
was O 0
predicted O 0
by O 0
a O 0
drop O 0
in O 0
EF O 0
determined O 0
during O 0
a O 0
cold O 0
pressor O 0
test O 0
. O 0

None O 0
of O 0
the O 0
other O 0
patients O 0
developed O 0
clinical O 0
cardiotoxicity B-Disease 0
, O 0
nor O 0
did O 0
the O 0
studied O 0
parameters O 0
change O 0
. O 0

The O 0
literature O 0
on O 0
this O 0
subject O 0
was O 0
also O 0
reviewed O 0
. O 0

Based O 0
on O 0
the O 0
combined O 0
data O 0
from O 0
the O 0
present O 0
study O 0
and O 0
the O 0
literature O 0
, O 0
we O 0
suggest O 0
that O 0
MMC B-Chemical 0
- O 0
related O 0
cardiotoxicity B-Disease 0
is O 0
dose O 0
dependent O 0
, O 0
occurring O 0
at O 0
cumulative O 0
dose O 0
levels O 0
of O 0
30 O 0
mg O 0
m O 0
- O 0
2 O 0
or O 0
more O 0
, O 0
mainly O 0
in O 0
patients O 0
also O 0
( O 0
previously O 0
or O 0
simultaneously O 0
) O 0
treated O 0
with O 0
doxorubicin B-Chemical 0
. O 0

The O 0
incidence O 0
is O 0
likely O 0
to O 0
be O 0
less O 0
than O 0
10 O 0
% O 0
even O 0
for O 0
this O 0
risk O 0
group O 0
. O 0

Reversible O 0
cerebral B-Disease 0
lesions I-Disease 0
associated O 0
with O 0
tiazofurin B-Chemical 0
usage O 0
: O 0
MR O 0
demonstration O 0
. O 0

Tiazofurin B-Chemical 0
is O 0
an O 0
experimental O 0
chemotherapeutic O 0
agent O 0
currently O 0
undergoing O 0
clinical O 0
evaluation O 0
. O 0

We O 0
report O 0
our O 0
results O 0
with O 0
magnetic O 0
resonance O 0
( O 0
MR O 0
) O 0
in O 0
demonstrating O 0
reversible O 0
cerebral B-Disease 0
abnormalities I-Disease 0
concurrent O 0
with O 0
the O 0
use O 0
of O 0
this O 0
drug O 0
. O 0

The O 0
abnormalities O 0
on O 0
MR O 0
were O 0
correlated O 0
with O 0
findings O 0
on O 0
CT O 0
as O 0
well O 0
as O 0
with O 0
cerebral O 0
angiography O 0
. O 0

The O 0
utility O 0
of O 0
MR O 0
in O 0
the O 0
evaluation O 0
of O 0
patients O 0
receiving O 0
this O 0
new O 0
agent O 0
is O 0
illustrated O 0
. O 0

Receptor O 0
mechanisms O 0
of O 0
nicotine B-Chemical 0
- O 0
induced O 0
locomotor B-Disease 0
hyperactivity I-Disease 0
in O 0
chronic O 0
nicotine B-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

Rats O 0
were O 0
pretreated O 0
with O 0
saline O 0
or O 0
nicotine B-Chemical 0
( O 0
1 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
per O 0
day O 0
) O 0
by O 0
subcutaneously O 0
implanting O 0
each O 0
animal O 0
with O 0
an O 0
Alzet O 0
osmotic O 0
mini O 0
- O 0
pump O 0
which O 0
continuously O 0
released O 0
saline O 0
or O 0
nicotine B-Chemical 0
for O 0
1 O 0
, O 0
5 O 0
and O 0
14 O 0
days O 0
. O 0

At O 0
the O 0
end O 0
of O 0
each O 0
pretreatment O 0
period O 0
, O 0
animals O 0
were O 0
used O 0
for O 0
( O 0
i O 0
) O 0
determining O 0
their O 0
locomotor O 0
response O 0
to O 0
acutely O 0
injected O 0
nicotine B-Chemical 0
( O 0
0 O 0
. O 0
2 O 0
mg O 0
/ O 0
kg O 0
, O 0
s O 0
. O 0
c O 0
. O 0
) O 0
and O 0
( O 0
ii O 0
) O 0
measuring O 0
the O 0
density O 0
of O 0
L O 0
- O 0
[ O 0
3H O 0
] O 0
nicotine B-Chemical 0
and O 0
[ O 0
3H O 0
] O 0
spiperone B-Chemical 0
binding O 0
sites O 0
in O 0
the O 0
striatum O 0
. O 0

We O 0
observed O 0
no O 0
changes O 0
in O 0
nicotine B-Chemical 0
- O 0
induced O 0
locomotor O 0
response O 0
, O 0
striatal O 0
L O 0
- O 0
[ O 0
3H O 0
] O 0
nicotine B-Chemical 0
and O 0
[ O 0
3H O 0
] O 0
spiperone B-Chemical 0
binding O 0
in O 0
the O 0
animals O 0
pretreated O 0
with O 0
nicotine B-Chemical 0
for O 0
1 O 0
day O 0
. O 0

In O 0
rats O 0
which O 0
were O 0
pretreated O 0
with O 0
nicotine B-Chemical 0
for O 0
5 O 0
days O 0
, O 0
there O 0
was O 0
a O 0
significant O 0
increase O 0
in O 0
the O 0
nicotine B-Chemical 0
- O 0
stimulated O 0
locomotor O 0
response O 0
which O 0
was O 0
associated O 0
with O 0
an O 0
increase O 0
in O 0
the O 0
number O 0
of O 0
L O 0
- O 0
[ O 0
3H O 0
] O 0
nicotine B-Chemical 0
binding O 0
sites O 0
and O 0
also O 0
with O 0
an O 0
elevated O 0
dopamine B-Chemical 0
( O 0
DA B-Chemical 0
) O 0
level O 0
in O 0
the O 0
striatum O 0
. O 0

The O 0
number O 0
of O 0
striatal O 0
[ O 0
3H O 0
] O 0
spiperone B-Chemical 0
binding O 0
sites O 0
was O 0
not O 0
affected O 0
. O 0

In O 0
animals O 0
pretreated O 0
with O 0
nicotine B-Chemical 0
for O 0
14 O 0
days O 0
, O 0
the O 0
nicotine B-Chemical 0
- O 0
induced O 0
locomotor O 0
response O 0
remained O 0
to O 0
be O 0
potentiated O 0
. O 0

However O 0
, O 0
this O 0
response O 0
was O 0
correlated O 0
with O 0
an O 0
elevated O 0
number O 0
of O 0
striatal O 0
[ O 0
3H O 0
] O 0
spiperone B-Chemical 0
binding O 0
sites O 0
, O 0
whereas O 0
the O 0
number O 0
of O 0
striatal O 0
L O 0
- O 0
[ O 0
3H O 0
] O 0
nicotine B-Chemical 0
binding O 0
sites O 0
and O 0
the O 0
striatal O 0
DA B-Chemical 0
level O 0
were O 0
normal O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
chronic O 0
nicotine B-Chemical 0
- O 0
treated O 0
rats O 0
develop O 0
locomotor B-Disease 0
hyperactivity I-Disease 0
in O 0
response O 0
to O 0
nicotine B-Chemical 0
initially O 0
due O 0
to O 0
increases O 0
of O 0
both O 0
the O 0
density O 0
of O 0
nicotinic O 0
receptors O 0
and O 0
DA B-Chemical 0
concentration O 0
, O 0
followed O 0
by O 0
inducing O 0
DA B-Chemical 0
receptor O 0
supersensitivity O 0
in O 0
the O 0
striatum O 0
. O 0

Amelioration O 0
of O 0
bendrofluazide B-Chemical 0
- O 0
induced O 0
hypokalemia B-Disease 0
by O 0
timolol B-Chemical 0
. O 0

The O 0
beta O 0
adrenergic O 0
blocking O 0
drug O 0
, O 0
timolol B-Chemical 0
, O 0
tended O 0
to O 0
correct O 0
the O 0
hypokalemia B-Disease 0
of O 0
short O 0
- O 0
term O 0
bendrofluazide B-Chemical 0
treatment O 0
in O 0
6 O 0
healthy O 0
male O 0
subjects O 0
and O 0
although O 0
the O 0
effect O 0
was O 0
small O 0
it O 0
was O 0
significant O 0
. O 0

Timolol B-Chemical 0
also O 0
reduced O 0
the O 0
rise O 0
in O 0
plasma O 0
aldosterone B-Chemical 0
and O 0
urine O 0
potassium B-Chemical 0
excretion O 0
following O 0
bendrofluazide B-Chemical 0
and O 0
increased O 0
the O 0
urine O 0
sodium B-Chemical 0
/ O 0
potassium B-Chemical 0
ratio O 0
. O 0

There O 0
was O 0
no O 0
evidence O 0
of O 0
a O 0
shift O 0
of O 0
potassium B-Chemical 0
from O 0
the O 0
intracellular O 0
to O 0
the O 0
extracellular O 0
space O 0
. O 0

St B-Disease 0
. I-Disease 0
Anthony I-Disease 0
' I-Disease 0
s I-Disease 0
fire I-Disease 0
, O 0
then O 0
and O 0
now O 0
: O 0
a O 0
case O 0
report O 0
and O 0
historical O 0
review O 0
. O 0

A O 0
rare O 0
case O 0
of O 0
morbid O 0
vasospasm B-Disease 0
, O 0
together O 0
with O 0
striking O 0
angiographic O 0
findings O 0
, O 0
is O 0
described O 0
secondary O 0
to O 0
the O 0
ingestion O 0
of O 0
methysergide B-Chemical 0
by O 0
a O 0
48 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
. O 0

A O 0
brief O 0
review O 0
of O 0
the O 0
literature O 0
on O 0
similar O 0
cases O 0
is O 0
presented O 0
. O 0

A O 0
discussion O 0
of O 0
the O 0
history O 0
of O 0
ergot B-Chemical 0
includes O 0
its O 0
original O 0
discovery O 0
, O 0
the O 0
epidemics O 0
of O 0
gangrene B-Disease 0
that O 0
it O 0
has O 0
caused O 0
through O 0
the O 0
ages O 0
and O 0
its O 0
past O 0
and O 0
present O 0
role O 0
in O 0
the O 0
management O 0
of O 0
migraine B-Disease 0
headache I-Disease 0
. O 0

Despite O 0
the O 0
advent O 0
of O 0
calcium B-Chemical 0
channel O 0
blockers O 0
and O 0
beta O 0
- O 0
adrenergic O 0
antagonists O 0
, O 0
ergot B-Chemical 0
preparations O 0
continue O 0
to O 0
play O 0
a O 0
major O 0
role O 0
in O 0
migraine B-Disease 0
therapy O 0
, O 0
so O 0
that O 0
the O 0
danger O 0
of O 0
St B-Disease 0
. I-Disease 0
Anthony I-Disease 0
' I-Disease 0
s I-Disease 0
fire I-Disease 0
persists O 0
. O 0

Cardiac O 0
transplantation O 0
: O 0
improved O 0
quality O 0
of O 0
survival O 0
with O 0
a O 0
modified O 0
immunosuppressive O 0
protocol O 0
. O 0

The O 0
effects O 0
on O 0
renal O 0
function O 0
on O 0
two O 0
different O 0
immunosuppressive O 0
protocols O 0
were O 0
evaluated O 0
retrospectively O 0
in O 0
two O 0
subsequent O 0
groups O 0
of O 0
heart O 0
transplant O 0
recipients O 0
. O 0

In O 0
group O 0
I O 0
, O 0
cyclosporine B-Chemical 0
was O 0
given O 0
before O 0
the O 0
procedure O 0
at O 0
a O 0
loading O 0
dose O 0
of O 0
17 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
and O 0
then O 0
continued O 0
after O 0
the O 0
procedure O 0
to O 0
keep O 0
a O 0
whole O 0
blood O 0
level O 0
about O 0
1000 O 0
ng O 0
/ O 0
ml O 0
. O 0

In O 0
group O 0
II O 0
, O 0
cyclosporine B-Chemical 0
was O 0
started O 0
only O 0
after O 0
the O 0
procedure O 0
at O 0
a O 0
lower O 0
dosage O 0
and O 0
was O 0
complemented O 0
by O 0
azathioprine B-Chemical 0
, O 0
which O 0
was O 0
used O 0
for O 0
the O 0
first O 0
postoperative O 0
week O 0
. O 0

Group O 0
II O 0
showed O 0
a O 0
better O 0
perioperative O 0
renal O 0
function O 0
as O 0
determined O 0
by O 0
serum O 0
blood O 0
urea B-Chemical 0
nitrogen I-Chemical 0
and O 0
serum O 0
creatinine B-Chemical 0
levels O 0
. O 0

Group O 0
II O 0
also O 0
showed O 0
a O 0
significant O 0
decrease O 0
of O 0
chronic O 0
nephrotoxicity B-Disease 0
secondary O 0
to O 0
long O 0
- O 0
term O 0
therapy O 0
with O 0
cyclosporine B-Chemical 0
. O 0

Despite O 0
this O 0
improvement O 0
in O 0
late O 0
renal O 0
function O 0
, O 0
group O 0
II O 0
still O 0
shows O 0
a O 0
slow O 0
rise O 0
in O 0
serum O 0
creatinine B-Chemical 0
. O 0

We O 0
think O 0
that O 0
even O 0
these O 0
lower O 0
dosages O 0
of O 0
cyclosporine B-Chemical 0
can O 0
cause O 0
chronic O 0
nephrotoxicity B-Disease 0
and O 0
that O 0
further O 0
modification O 0
of O 0
the O 0
immunosuppressive O 0
regimen O 0
is O 0
required O 0
to O 0
completely O 0
abolish O 0
this O 0
toxic O 0
side O 0
effect O 0
. O 0

Ethopropazine B-Chemical 0
and O 0
benztropine B-Chemical 0
in O 0
neuroleptic O 0
- O 0
induced O 0
parkinsonism B-Disease 0
. O 0

In O 0
a O 0
12 O 0
- O 0
week O 0
controlled O 0
study O 0
ethopropazine B-Chemical 0
was O 0
compared O 0
to O 0
benztropine B-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
parkinsonism B-Disease 0
induced O 0
by O 0
fluphenazine B-Chemical 0
enanthate I-Chemical 0
in O 0
60 O 0
schizophrenic B-Disease 0
outpatients O 0
. O 0

Ethopropazine B-Chemical 0
and O 0
benztropine B-Chemical 0
were O 0
found O 0
to O 0
be O 0
equally O 0
effective O 0
in O 0
controlling O 0
parkinsonian B-Disease 0
symptoms I-Disease 0
and O 0
were O 0
as O 0
efficacious O 0
as O 0
procyclidine B-Chemical 0
, O 0
their O 0
previous O 0
antiparkinsonian O 0
drug O 0
. O 0

However O 0
, O 0
benztropine B-Chemical 0
treated O 0
patients O 0
had O 0
a O 0
significant O 0
increase O 0
in O 0
tardive B-Disease 0
dyskinesia I-Disease 0
compared O 0
to O 0
their O 0
condition O 0
during O 0
procyclindine B-Chemical 0
treatment O 0
, O 0
and O 0
significantly O 0
more O 0
anxiety B-Disease 0
and O 0
depression B-Disease 0
than O 0
ethopropazine B-Chemical 0
treated O 0
patients O 0
. O 0

This O 0
suggests O 0
that O 0
benztropine B-Chemical 0
is O 0
not O 0
the O 0
anticholinergic O 0
drug O 0
of O 0
choice O 0
in O 0
the O 0
treatment O 0
of O 0
neuroleptic O 0
- O 0
induced O 0
parkinsonian B-Disease 0
symptoms I-Disease 0
, O 0
because O 0
of O 0
its O 0
more O 0
toxic O 0
central O 0
and O 0
peripheral O 0
atropinic O 0
effect O 0
. O 0

Quinidine B-Chemical 0
phenylethylbarbiturate I-Chemical 0
- O 0
induced O 0
fulminant O 0
hepatitis B-Disease 0
in O 0
a O 0
pregnant O 0
woman O 0
. O 0

A O 0
case O 0
report O 0
. O 0

We O 0
report O 0
the O 0
case O 0
of O 0
a O 0
19 O 0
- O 0
year O 0
- O 0
old O 0
Laotian O 0
patient O 0
affected O 0
by O 0
fulminant O 0
hepatitis B-Disease 0
during O 0
the O 0
third O 0
trimester O 0
of O 0
her O 0
pregnancy O 0
after O 0
a O 0
1 O 0
- O 0
month O 0
administration O 0
of O 0
quinidine B-Chemical 0
phenylethylbarbiturate I-Chemical 0
. O 0

After O 0
delivery O 0
, O 0
the O 0
patient O 0
underwent O 0
orthotopic O 0
liver O 0
transplantation O 0
. O 0

The O 0
patient O 0
was O 0
in O 0
good O 0
condition O 0
16 O 0
months O 0
after O 0
liver O 0
transplantation O 0
. O 0

Quinidine B-Chemical 0
itself O 0
or O 0
phenylethylbarbiturate B-Chemical 0
may O 0
be O 0
responsible O 0
for O 0
fulminant O 0
hepatitis B-Disease 0
in O 0
this O 0
patient O 0
. O 0

Mechanisms O 0
of O 0
myocardial B-Disease 0
ischemia I-Disease 0
induced O 0
by O 0
epinephrine B-Chemical 0
: O 0
comparison O 0
with O 0
exercise O 0
- O 0
induced O 0
ischemia B-Disease 0
. O 0

The O 0
role O 0
of O 0
epinephrine B-Chemical 0
in O 0
eliciting O 0
myocardial B-Disease 0
ischemia I-Disease 0
was O 0
examined 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

Objective O 0
signs O 0
of O 0
ischemia B-Disease 0
and O 0
factors O 0
increasing O 0
myocardial O 0
oxygen B-Chemical 0
consumption O 0
were O 0
compared O 0
during O 0
epinephrine B-Chemical 0
infusion O 0
and O 0
supine O 0
bicycle O 0
exercise O 0
. O 0

Both O 0
epinephrine B-Chemical 0
and O 0
exercise O 0
produced O 0
myocardial B-Disease 0
ischemia I-Disease 0
as O 0
evidenced O 0
by O 0
ST O 0
segment O 0
depression B-Disease 0
and O 0
angina B-Disease 0
. O 0

However O 0
, O 0
the O 0
mechanisms O 0
of O 0
myocardial B-Disease 0
ischemia I-Disease 0
induced O 0
by O 0
epinephrine B-Chemical 0
were O 0
significantly O 0
different O 0
from O 0
those O 0
of O 0
exercise O 0
. O 0

Exercise O 0
- O 0
induced O 0
myocardial B-Disease 0
ischemia I-Disease 0
was O 0
marked O 0
predominantly O 0
by O 0
increased O 0
heart O 0
rate O 0
and O 0
rate O 0
- O 0
pressure O 0
product O 0
with O 0
a O 0
minor O 0
contribution O 0
of O 0
end O 0
- O 0
diastolic O 0
volume O 0
, O 0
while O 0
epinephrine B-Chemical 0
- O 0
induced O 0
ischemia B-Disease 0
was O 0
characterized O 0
by O 0
a O 0
marked O 0
increase O 0
in O 0
contractility O 0
and O 0
a O 0
less O 0
pronounced O 0
increase O 0
in O 0
heart O 0
rate O 0
and O 0
rate O 0
- O 0
pressure O 0
product O 0
. O 0

These O 0
findings O 0
indicate O 0
that O 0
ischemia B-Disease 0
produced O 0
by O 0
epinephrine B-Chemical 0
, O 0
as O 0
may O 0
occur O 0
during O 0
states O 0
of O 0
emotional O 0
distress O 0
, O 0
has O 0
a O 0
mechanism O 0
distinct O 0
from O 0
that O 0
due O 0
to O 0
physical O 0
exertion O 0
. O 0

Recent O 0
preclinical O 0
and O 0
clinical O 0
studies O 0
with O 0
the O 0
thymidylate O 0
synthase O 0
inhibitor O 0
N10 B-Chemical 0
- I-Chemical 0
propargyl I-Chemical 0
- I-Chemical 0
5 I-Chemical 0
, I-Chemical 0
8 I-Chemical 0
- I-Chemical 0
dideazafolic I-Chemical 0
acid I-Chemical 0
( O 0
CB B-Chemical 0
3717 I-Chemical 0
) O 0
. O 0

CB B-Chemical 0
3717 I-Chemical 0
, O 0
N10 B-Chemical 0
- I-Chemical 0
propargyl I-Chemical 0
- I-Chemical 0
5 I-Chemical 0
, I-Chemical 0
8 I-Chemical 0
- I-Chemical 0
dideazafolic I-Chemical 0
acid I-Chemical 0
, O 0
is O 0
a O 0
tight O 0
- O 0
binding O 0
inhibitor O 0
of O 0
thymidylate O 0
synthase O 0
( O 0
TS O 0
) O 0
whose O 0
cytotoxicity B-Disease 0
is O 0
mediated O 0
solely O 0
through O 0
the O 0
inhibition O 0
of O 0
this O 0
enzyme O 0
. O 0

Recent O 0
preclinical O 0
studies O 0
have O 0
focused O 0
on O 0
the O 0
intracellular O 0
formation O 0
of O 0
CB B-Chemical 0
3717 I-Chemical 0
polyglutamates O 0
. O 0

Following O 0
a O 0
12 O 0
- O 0
hour O 0
exposure O 0
of O 0
L1210 O 0
cells O 0
to O 0
50 O 0
microM O 0
[ O 0
3H O 0
] O 0
CB B-Chemical 0
3717 I-Chemical 0
, O 0
30 O 0
% O 0
of O 0
the O 0
extractable O 0
radioactivity O 0
could O 0
be O 0
accounted O 0
for O 0
as O 0
CB B-Chemical 0
3717 I-Chemical 0
tetra O 0
- O 0
and O 0
pentaglutamate O 0
, O 0
as O 0
determined O 0
by O 0
high O 0
- O 0
pressure O 0
liquid O 0
chromatography O 0
( O 0
HPLC O 0
) O 0
analyses O 0
. O 0

As O 0
inhibitors O 0
of O 0
isolated O 0
L1210 O 0
TS O 0
, O 0
CB O 0
3717 O 0
di O 0
- O 0
, O 0
tri O 0
- O 0
, O 0
tetra O 0
- O 0
and O 0
pentaglutamate O 0
are O 0
26 O 0
- O 0
, O 0
87 O 0
- O 0
, O 0
119 O 0
- O 0
and O 0
114 O 0
- O 0
fold O 0
more O 0
potent O 0
than O 0
CB B-Chemical 0
3717 I-Chemical 0
, O 0
respectively O 0
, O 0
and O 0
their O 0
formation O 0
may O 0
, O 0
therefore O 0
, O 0
be O 0
an O 0
important O 0
determinant O 0
of O 0
CB B-Chemical 0
3717 I-Chemical 0
cytotoxicity B-Disease 0
. O 0

In O 0
early O 0
clinical O 0
studies O 0
with O 0
CB B-Chemical 0
3717 I-Chemical 0
, O 0
activity O 0
has O 0
been O 0
seen O 0
in O 0
breast B-Disease 0
cancer I-Disease 0
, O 0
ovarian B-Disease 0
cancer I-Disease 0
, O 0
hepatoma B-Disease 0
, O 0
and O 0
mesothelioma B-Disease 0
. O 0

Toxicities B-Disease 0
included O 0
hepatotoxicity B-Disease 0
, O 0
malaise B-Disease 0
, O 0
and O 0
dose O 0
- O 0
limiting O 0
nephrotoxicity B-Disease 0
. O 0

This O 0
latter O 0
effect O 0
is O 0
thought O 0
to O 0
be O 0
due O 0
to O 0
drug O 0
precipitation O 0
within O 0
the O 0
renal O 0
tubule O 0
as O 0
a O 0
result O 0
of O 0
the O 0
poor O 0
solubility O 0
of O 0
CB B-Chemical 0
3717 I-Chemical 0
under O 0
acidic O 0
conditions O 0
. O 0

In O 0
an O 0
attempt O 0
to O 0
overcome O 0
this O 0
problem O 0
, O 0
a O 0
clinical O 0
trial O 0
of O 0
CB B-Chemical 0
3717 I-Chemical 0
administered O 0
with O 0
alkaline O 0
diuresis O 0
is O 0
under O 0
way O 0
. O 0

Preliminary O 0
results O 0
at O 0
400 O 0
and O 0
500 O 0
mg O 0
/ O 0
m2 O 0
suggest O 0
that O 0
a O 0
reduction O 0
in O 0
nephrotoxicity B-Disease 0
may O 0
have O 0
been O 0
achieved O 0
with O 0
only O 0
1 O 0
instance O 0
of O 0
renal B-Disease 0
toxicity I-Disease 0
in O 0
10 O 0
patients O 0
. O 0

Hepatotoxicity B-Disease 0
and O 0
malaise B-Disease 0
are O 0
again O 0
the O 0
most O 0
frequent O 0
side O 0
effects O 0
. O 0

Evidence O 0
of O 0
antitumor O 0
activity O 0
has O 0
been O 0
seen O 0
in O 0
3 O 0
patients O 0
. O 0

Pharmacokinetic O 0
investigations O 0
have O 0
shown O 0
that O 0
alkaline O 0
diuresis O 0
does O 0
not O 0
alter O 0
CB B-Chemical 0
3717 I-Chemical 0
plasma O 0
levels O 0
or O 0
urinary O 0
excretion O 0
and O 0
that O 0
satisfactory O 0
urinary O 0
alkalinization O 0
can O 0
be O 0
readily O 0
achieved O 0
. O 0

Type B-Disease 0
B I-Disease 0
hepatitis I-Disease 0
after O 0
needle O 0
- O 0
stick O 0
exposure O 0
: O 0
prevention O 0
with O 0
hepatitis B-Disease 0
B I-Disease 0
immune O 0
globulin O 0
. O 0

Final O 0
report O 0
of O 0
the O 0
Veterans O 0
Administration O 0
Cooperative O 0
Study O 0
. 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
immune O 0
serum O 0
globulin O 0
( O 0
ISG O 0
) O 0
were O 0
examined O 0
in O 0
a O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
trial O 0
to O 0
assess O 0
their O 0
relative O 0
efficacies O 0
in O 0
preventing O 0
type B-Disease 0
B I-Disease 0
hepatitis I-Disease 0
after O 0
needle O 0
- O 0
stick O 0
exposure O 0
to 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
- O 0
positive O 0
donors O 0
. O 0

Clinical O 0
hepatitis B-Disease 0
developed O 0
in O 0
1 O 0
. O 0
4 O 0
% O 0
of O 0
HBIG O 0
and O 0
in O 0
5 O 0
. O 0
9 O 0
% O 0
of O 0
ISG O 0
recipients O 0
( O 0
P O 0
= O 0
0 O 0
. O 0
016 O 0
) O 0
, O 0
and O 0
seroconversion O 0
( O 0
anti O 0
- O 0
HBs O 0
) O 0
occurred O 0
in O 0
5 O 0
. O 0
6 O 0
% O 0
and O 0
20 O 0
. O 0
7 O 0
% O 0
of O 0
them O 0
respectively 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

Mild O 0
and O 0
transient O 0
side O 0
- O 0
effects O 0
were O 0
noted O 0
in O 0
3 O 0
. O 0
0 O 0
% O 0
of O 0
ISG O 0
and O 0
in O 0
3 O 0
. O 0
2 O 0
% O 0
of O 0
HBIG O 0
recipients O 0
. O 0

Available O 0
donor O 0
sera O 0
were O 0
examined O 0
for O 0
DNA O 0
polymerase O 0
( O 0
DNAP O 0
) O 0
and O 0
e O 0
antigen O 0
and O 0
antibody O 0
( O 0
HBeAg B-Chemical 0
; O 0
anti O 0
- O 0
HBE O 0
) O 0
. O 0

Both O 0
DNAP O 0
and O 0
HBeAg B-Chemical 0
showed O 0
a O 0
highly O 0
statistically O 0
significant O 0
correlation O 0
with O 0
the O 0
infectivity O 0
of O 0
HBsAg B-Chemical 0
- O 0
positive O 0
donors O 0
. O 0

Hepatitis B-Disease 0
B I-Disease 0
immune O 0
globulin O 0
remained O 0
significantly O 0
superior O 0
to O 0
ISG O 0
in O 0
preventing O 0
type B-Disease 0
B I-Disease 0
hepatitis I-Disease 0
even O 0
when O 0
the O 0
analysis O 0
was O 0
confined O 0
to O 0
these O 0
two O 0
high O 0
- O 0
risk O 0
subgroups O 0
. O 0

The O 0
efficacy O 0
of O 0
ISG O 0
in O 0
preventing O 0
type B-Disease 0
B I-Disease 0
hepatitis I-Disease 0
cannot O 0
be O 0
ascertained O 0
because O 0
a O 0
true O 0
placebo O 0
group O 0
was O 0
not O 0
included O 0
. O 0

Production O 0
of O 0
autochthonous O 0
prostate B-Disease 0
cancer I-Disease 0
in O 0
Lobund O 0
- O 0
Wistar O 0
rats O 0
by O 0
treatments O 0
with O 0
N B-Chemical 0
- I-Chemical 0
nitroso I-Chemical 0
- I-Chemical 0
N I-Chemical 0
- I-Chemical 0
methylurea I-Chemical 0
and O 0
testosterone B-Chemical 0
. O 0

More O 0
than O 0
50 O 0
% O 0
of O 0
Lobund O 0
- O 0
Wistar O 0
( O 0
L O 0
- O 0
W O 0
) O 0
strain O 0
rats O 0
developed O 0
large O 0
, O 0
palpable O 0
prostate B-Disease 0
adenocarcinomas I-Disease 0
( O 0
PAs B-Disease 0
) O 0
following O 0
treatments O 0
with O 0
N B-Chemical 0
- I-Chemical 0
nitroso I-Chemical 0
- I-Chemical 0
N I-Chemical 0
- I-Chemical 0
methylurea I-Chemical 0
( O 0
CAS O 0
: O 0
684 O 0
- O 0
93 O 0
- O 0
5 O 0
) O 0
and O 0
testosterone B-Chemical 0
propionate I-Chemical 0
[ O 0
( O 0
TP B-Chemical 0
) O 0
CAS O 0
: O 0
57 O 0
- O 0
85 O 0
- O 0
2 O 0
] O 0
, O 0
and O 0
most O 0
of O 0
the O 0
tumor B-Disease 0
- O 0
bearing O 0
rats O 0
manifested O 0
metastatic O 0
lesions O 0
. O 0

The O 0
incubation O 0
periods O 0
averaged O 0
10 O 0
. O 0
6 O 0
months O 0
. O 0

Within O 0
the O 0
same O 0
timeframe O 0
, O 0
no O 0
L O 0
- O 0
W O 0
rat O 0
developed O 0
a O 0
similar O 0
palpable O 0
PA B-Disease 0
when O 0
treated O 0
only O 0
with O 0
TP B-Chemical 0
. O 0

In O 0
L O 0
- O 0
W O 0
rats O 0
, O 0
TP B-Chemical 0
acted O 0
as O 0
a O 0
tumor B-Disease 0
enhancement O 0
agent O 0
, O 0
with O 0
primary O 0
emphasis O 0
on O 0
the O 0
development O 0
of O 0
prostate B-Disease 0
cancer I-Disease 0
. O 0

Relative O 0
efficacy O 0
and O 0
toxicity B-Disease 0
of O 0
netilmicin B-Chemical 0
and O 0
tobramycin B-Chemical 0
in O 0
oncology O 0
patients O 0
. O 0

We O 0
prospectively O 0
compared O 0
the O 0
efficacy O 0
and O 0
safety O 0
of O 0
netilmicin B-Chemical 0
sulfate I-Chemical 0
or O 0
tobramycin B-Chemical 0
sulfate I-Chemical 0
in O 0
conjunction O 0
with O 0
piperacillin B-Chemical 0
sodium I-Chemical 0
in O 0
118 O 0
immunocompromised O 0
patients O 0
with O 0
presumed O 0
severe O 0
infections B-Disease 0
. O 0

The O 0
two O 0
treatment O 0
regimens O 0
were O 0
equally O 0
efficacious O 0
. O 0

Nephrotoxicity B-Disease 0
occurred O 0
in O 0
a O 0
similar O 0
proportion O 0
in O 0
patients O 0
treated O 0
with O 0
netilmicin B-Chemical 0
and O 0
tobramycin B-Chemical 0
( O 0
17 O 0
% O 0
vs O 0
11 O 0
% O 0
) O 0
. O 0

Ototoxicity B-Disease 0
occurred O 0
in O 0
four O 0
( O 0
9 O 0
. O 0
5 O 0
% O 0
) O 0
of O 0
42 O 0
netilmicin B-Chemical 0
and O 0
piperacillin B-Chemical 0
and O 0
in O 0
12 O 0
( O 0
22 O 0
% O 0
) O 0
of O 0
54 O 0
tobramycin B-Chemical 0
and O 0
piperacillin B-Chemical 0
- O 0
treated O 0
patients O 0
. O 0

Of O 0
those O 0
evaluated O 0
with O 0
posttherapy O 0
audiograms O 0
, O 0
three O 0
of O 0
four O 0
netilmicin B-Chemical 0
and O 0
piperacillin B-Chemical 0
- O 0
treated O 0
patients O 0
had O 0
auditory O 0
thresholds O 0
return O 0
to O 0
baseline O 0
compared O 0
with O 0
one O 0
of O 0
nine O 0
tobramycin B-Chemical 0
and O 0
piperacillin B-Chemical 0
- O 0
treated O 0
patients O 0
. O 0

The O 0
number O 0
of O 0
greater O 0
than O 0
or O 0
equal O 0
to O 0
15 O 0
- O 0
dB O 0
increases O 0
in O 0
auditory O 0
threshold O 0
as O 0
a O 0
proportion O 0
of O 0
total O 0
greater O 0
than O 0
or O 0
equal O 0
to O 0
15 O 0
- O 0
dB O 0
changes O 0
( O 0
increases O 0
and O 0
decreases O 0
) O 0
was O 0
significantly O 0
lower O 0
in O 0
netilmicin B-Chemical 0
and O 0
piperacillin B-Chemical 0
- O 0
vs O 0
tobramycin B-Chemical 0
and O 0
piperacillin B-Chemical 0
- O 0
treated O 0
patients O 0
( O 0
18 O 0
of O 0
78 O 0
vs O 0
67 O 0
of O 0
115 O 0
) O 0
. O 0

We O 0
conclude O 0
that O 0
aminoglycoside B-Chemical 0
- O 0
associated O 0
ototoxicity B-Disease 0
was O 0
less O 0
severe O 0
and O 0
more O 0
often O 0
reversible O 0
with O 0
netilmicin B-Chemical 0
than O 0
with O 0
tobramycin B-Chemical 0
. O 0

Urinary O 0
enzymes O 0
and O 0
protein O 0
patterns O 0
as O 0
indicators O 0
of O 0
injury B-Disease 0
to I-Disease 0
different I-Disease 0
regions I-Disease 0
of I-Disease 0
the I-Disease 0
kidney I-Disease 0
. O 0

Acute B-Disease 0
experimental I-Disease 0
models I-Disease 0
of I-Disease 0
renal I-Disease 0
damage I-Disease 0
to O 0
the O 0
proximal O 0
tubular O 0
, O 0
glomerular O 0
, O 0
and O 0
papillary O 0
regions O 0
of O 0
the O 0
rat O 0
were O 0
produced O 0
by O 0
administration O 0
of O 0
hexachloro B-Chemical 0
- I-Chemical 0
1 I-Chemical 0
: I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
butadiene I-Chemical 0
( O 0
HCBD B-Chemical 0
) O 0
, O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
( O 0
PAN B-Chemical 0
) O 0
, O 0
and O 0
2 B-Chemical 0
- I-Chemical 0
bromoethylamine I-Chemical 0
( O 0
BEA B-Chemical 0
) O 0
, O 0
respectively O 0
. O 0

Several O 0
routine O 0
indicators O 0
of O 0
nephrotoxicity B-Disease 0
, O 0
the O 0
enzymes O 0
alkaline O 0
phosphatase O 0
and O 0
N O 0
- O 0
acetyl O 0
- O 0
beta O 0
- O 0
glucosaminidase O 0
, O 0
and O 0
the O 0
molecular O 0
weight O 0
of O 0
protein B-Disease 0
excretion I-Disease 0
were O 0
determined O 0
on O 0
urine O 0
samples O 0
. O 0

Tubular O 0
damage O 0
produced O 0
by O 0
HCBD B-Chemical 0
or O 0
BEA B-Chemical 0
was O 0
discriminated O 0
both O 0
quantitatively O 0
and O 0
qualitatively O 0
from O 0
glomerular B-Disease 0
damage I-Disease 0
produced O 0
by O 0
PAN B-Chemical 0
. O 0

The O 0
latter O 0
was O 0
characterized O 0
by O 0
a O 0
pronounced O 0
increase O 0
in O 0
protein B-Disease 0
excretion I-Disease 0
, O 0
especially O 0
proteins O 0
with O 0
molecular O 0
weight O 0
greater O 0
than O 0
40 O 0
, O 0
000 O 0
Da O 0
. O 0

In O 0
contrast O 0
, O 0
protein B-Disease 0
excretion I-Disease 0
in O 0
tubular O 0
damage O 0
was O 0
raised O 0
only O 0
slightly O 0
and O 0
characterized O 0
by O 0
excretion B-Disease 0
of I-Disease 0
proteins I-Disease 0
of O 0
a O 0
wide O 0
range O 0
of O 0
molecular O 0
weights O 0
. O 0

Proximal O 0
tubular O 0
damage O 0
caused O 0
by O 0
HCBD B-Chemical 0
and O 0
papillary O 0
damage O 0
caused O 0
by O 0
BEA B-Chemical 0
were O 0
distinguished O 0
both O 0
by O 0
conventional O 0
urinalysis O 0
( O 0
volume O 0
and O 0
specific O 0
gravity O 0
) O 0
and O 0
by O 0
measurement O 0
of O 0
the O 0
two O 0
urinary O 0
enzymes O 0
. O 0

Alkaline O 0
phosphatase O 0
and O 0
glucose B-Chemical 0
were O 0
markedly O 0
and O 0
transiently O 0
elevated O 0
in O 0
proximal O 0
tubular O 0
damage O 0
and O 0
N O 0
- O 0
acetyl O 0
- O 0
beta O 0
- O 0
glucosaminidase O 0
showed O 0
a O 0
sustained O 0
elevation O 0
in O 0
papillary O 0
damage O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
both O 0
selective O 0
urinary O 0
enzymes O 0
and O 0
the O 0
molecular O 0
weight O 0
pattern O 0
of O 0
urinary O 0
proteins O 0
can O 0
be O 0
used O 0
to O 0
provide O 0
diagnostic O 0
information O 0
about O 0
the O 0
possible O 0
site O 0
of O 0
renal B-Disease 0
damage I-Disease 0
. O 0

A O 0
catch O 0
in O 0
the O 0
Reye B-Disease 0
. O 0

Twenty O 0
- O 0
six O 0
cases O 0
of O 0
Reye B-Disease 0
syndrome I-Disease 0
from O 0
The O 0
Children O 0
' O 0
s O 0
Hospital O 0
, O 0
Camperdown O 0
, O 0
Australia O 0
, O 0
occurring O 0
between O 0
1973 O 0
and O 0
1982 O 0
were O 0
reviewed O 0
. O 0

Of O 0
these O 0
, O 0
20 O 0
cases O 0
met O 0
the O 0
US O 0
Public O 0
Health O 0
Service O 0
Centers O 0
for O 0
Disease O 0
Control O 0
criteria O 0
for O 0
the O 0
diagnosis O 0
of O 0
Reye B-Disease 0
syndrome I-Disease 0
. O 0

Aspirin B-Chemical 0
or O 0
salicylate B-Chemical 0
ingestion O 0
had O 0
occurred O 0
in O 0
only O 0
one O 0
of O 0
the O 0
20 O 0
cases O 0
( O 0
5 O 0
% O 0
) O 0
, O 0
and O 0
paracetamol B-Chemical 0
( O 0
acetaminophen B-Chemical 0
) O 0
had O 0
been O 0
administered O 0
in O 0
only O 0
six O 0
of O 0
the O 0
cases O 0
( O 0
30 O 0
% O 0
) O 0
. O 0

Pathologic O 0
confirmation O 0
of O 0
the O 0
diagnosis O 0
of O 0
Reye B-Disease 0
syndrome I-Disease 0
was O 0
accomplished O 0
in O 0
90 O 0
% O 0
of O 0
the O 0
cases O 0
. O 0

The O 0
incidence O 0
of O 0
Reye B-Disease 0
syndrome I-Disease 0
in O 0
New O 0
South O 0
Wales O 0
, O 0
Australia O 0
, O 0
is O 0
estimated O 0
from O 0
this O 0
study O 0
to O 0
be O 0
approximately O 0
nine O 0
cases O 0
per O 0
1 O 0
million O 0
children O 0
compared O 0
with O 0
recent O 0
US O 0
data O 0
of O 0
ten O 0
to O 0
20 O 0
cases O 0
per O 0
1 O 0
million O 0
children O 0
and O 0
three O 0
to O 0
seven O 0
cases O 0
per O 0
1 O 0
million O 0
children O 0
in O 0
Great O 0
Britain O 0
. O 0

The O 0
mortality O 0
for O 0
these O 0
Reye B-Disease 0
syndrome I-Disease 0
cases O 0
in O 0
Australia O 0
was O 0
45 O 0
% O 0
as O 0
compared O 0
with O 0
a O 0
32 O 0
% O 0
case O 0
- O 0
fatality O 0
rate O 0
in O 0
the O 0
United O 0
States O 0
. O 0

In O 0
Australia O 0
, O 0
the O 0
pediatric O 0
usage O 0
of O 0
aspirin B-Chemical 0
has O 0
been O 0
extremely O 0
low O 0
for O 0
the O 0
past O 0
25 O 0
years O 0
( O 0
less O 0
than O 0
1 O 0
% O 0
of O 0
total O 0
dosage O 0
units O 0
sold O 0
) O 0
, O 0
with O 0
paracetamol B-Chemical 0
( O 0
acetaminophen B-Chemical 0
) O 0
dominating O 0
the O 0
pediatric O 0
analgesic O 0
and O 0
antipyretic O 0
market O 0
. O 0

Reye B-Disease 0
syndrome I-Disease 0
may O 0
be O 0
disappearing O 0
from O 0
Australia O 0
despite O 0
a O 0
total O 0
lack O 0
of O 0
association O 0
with O 0
salicylates B-Chemical 0
or O 0
aspirin B-Chemical 0
ingestion O 0
, O 0
since O 0
there O 0
were O 0
no O 0
cases O 0
found O 0
at O 0
The O 0
Children O 0
' O 0
s O 0
Hospital O 0
in O 0
1983 O 0
, O 0
1984 O 0
, O 0
or O 0
1985 O 0
. O 0

Postpartum O 0
psychosis B-Disease 0
induced O 0
by O 0
bromocriptine B-Chemical 0
. O 0

Two O 0
multigravida O 0
patients O 0
with O 0
no O 0
prior O 0
psychiatric B-Disease 0
history O 0
were O 0
seen O 0
with O 0
postpartum O 0
psychosis B-Disease 0
, O 0
having O 0
received O 0
bromocriptine B-Chemical 0
for O 0
inhibition B-Disease 0
of I-Disease 0
lactation I-Disease 0
. O 0

Bromocriptine B-Chemical 0
given O 0
in O 0
high O 0
doses O 0
has O 0
been O 0
associated O 0
with O 0
psychosis B-Disease 0
in O 0
patients O 0
receiving O 0
the O 0
drug O 0
for O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

These O 0
cases O 0
demonstrate O 0
that O 0
bromocriptine B-Chemical 0
may O 0
cause O 0
psychosis B-Disease 0
even O 0
when O 0
given O 0
in O 0
low O 0
doses O 0
. O 0

Hyperglycemic B-Disease 0
acidotic I-Disease 0
coma I-Disease 0
and O 0
death O 0
in O 0
Kearns B-Disease 0
- I-Disease 0
Sayre I-Disease 0
syndrome I-Disease 0
. O 0

This O 0
paper O 0
presents O 0
the O 0
clinical O 0
and O 0
metabolic O 0
findings O 0
in O 0
two O 0
young O 0
boys O 0
with O 0
long O 0
- O 0
standing O 0
Kearns B-Disease 0
- I-Disease 0
Sayre I-Disease 0
syndrome I-Disease 0
. O 0

Following O 0
short O 0
exposure O 0
to O 0
oral O 0
prednisone B-Chemical 0
, O 0
both O 0
boys O 0
developed O 0
lethargy B-Disease 0
, O 0
increasing O 0
somnolence B-Disease 0
, O 0
polydipsia B-Disease 0
, O 0
polyphagia B-Disease 0
, O 0
and O 0
polyuria B-Disease 0
. O 0

Both O 0
presented O 0
in O 0
the O 0
emergency O 0
room O 0
with O 0
profound O 0
coma B-Disease 0
, O 0
hypotension B-Disease 0
, O 0
severe O 0
hyperglycemia B-Disease 0
, O 0
and O 0
acidosis B-Disease 0
. O 0

Nonketotic O 0
lactic B-Disease 0
acidosis I-Disease 0
was O 0
present O 0
in O 0
one O 0
and O 0
ketosis B-Disease 0
without O 0
a O 0
known O 0
serum O 0
lactate B-Chemical 0
level O 0
was O 0
present O 0
in O 0
the O 0
other O 0
. O 0

Respiratory B-Disease 0
failure I-Disease 0
rapidly O 0
ensued O 0
and O 0
both O 0
patients O 0
expired O 0
in O 0
spite O 0
of O 0
efforts O 0
at O 0
resuscitation O 0
. O 0

We O 0
believe O 0
these O 0
two O 0
cases O 0
represent O 0
a O 0
newly O 0
described O 0
and O 0
catastrophic O 0
metabolic B-Disease 0
- I-Disease 0
endocrine I-Disease 0
failure I-Disease 0
in O 0
the O 0
Kearns B-Disease 0
- I-Disease 0
Sayre I-Disease 0
syndrome I-Disease 0
. O 0

Experimental O 0
cyclosporine B-Chemical 0
nephrotoxicity B-Disease 0
: O 0
risk O 0
of O 0
concomitant O 0
chemotherapy O 0
. O 0

The O 0
role O 0
of O 0
cyclosporine B-Chemical 0
( O 0
CSA B-Chemical 0
) O 0
alone O 0
or O 0
in O 0
combination O 0
with O 0
various O 0
chemotherapeutics O 0
in O 0
the O 0
development O 0
of O 0
renal B-Disease 0
toxicity I-Disease 0
was O 0
evaluated O 0
in O 0
rats O 0
. O 0

Administration O 0
of O 0
20 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
CSA B-Chemical 0
for O 0
4 O 0
weeks O 0
caused O 0
renal O 0
functional O 0
and O 0
structural O 0
changes O 0
similar O 0
to O 0
those O 0
reported O 0
in O 0
man O 0
. O 0

The O 0
combined O 0
administration O 0
of O 0
CSA B-Chemical 0
and O 0
various O 0
chemotherapeutic O 0
drugs O 0
with O 0
a O 0
nephrotoxic B-Disease 0
potential O 0
, O 0
such O 0
as O 0
gentamicin B-Chemical 0
( O 0
at O 0
therapeutic O 0
doses O 0
) O 0
, O 0
amphothericin B-Chemical 0
B I-Chemical 0
and O 0
ketoconazole B-Chemical 0
, O 0
which O 0
are O 0
frequently O 0
used O 0
in O 0
immunosuppressed O 0
patients O 0
, O 0
did O 0
not O 0
aggravate O 0
the O 0
CSA B-Chemical 0
induced O 0
toxicity B-Disease 0
in O 0
the O 0
rat O 0
model O 0
. O 0

Gentamicin B-Chemical 0
at O 0
toxic O 0
doses O 0
, O 0
however O 0
, O 0
increased O 0
CSA B-Chemical 0
nephrotoxicity B-Disease 0
. O 0

Thus O 0
, O 0
the O 0
nephrotoxicity B-Disease 0
induced O 0
by O 0
CSA B-Chemical 0
has O 0
a O 0
different O 0
pathogenetic O 0
mechanism O 0
. O 0

Diuretics O 0
, O 0
potassium B-Chemical 0
and O 0
arrhythmias B-Disease 0
in O 0
hypertensive B-Disease 0
coronary B-Disease 0
disease I-Disease 0
. O 0

It O 0
has O 0
been O 0
proposed O 0
that O 0
modest O 0
changes O 0
in O 0
plasma O 0
potassium B-Chemical 0
can O 0
alter O 0
the O 0
tendency O 0
towards O 0
cardiac B-Disease 0
arrhythmias I-Disease 0
. O 0

If O 0
this O 0
were O 0
so O 0
, O 0
patients O 0
with O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
might O 0
be O 0
especially O 0
susceptible O 0
. O 0

Thus O 0
, O 0
myocardial O 0
electrical O 0
excitability O 0
was O 0
measured O 0
in O 0
patients O 0
with O 0
mild O 0
essential O 0
hypertension B-Disease 0
and O 0
known O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
after O 0
8 O 0
weeks O 0
of O 0
treatment O 0
with O 0
a O 0
potassium B-Chemical 0
- O 0
conserving O 0
diuretic O 0
( O 0
amiloride B-Chemical 0
) O 0
and O 0
a O 0
similar O 0
period O 0
on O 0
a O 0
potassium B-Chemical 0
- O 0
losing O 0
diuretic O 0
( O 0
chlorthalidone B-Chemical 0
) O 0
in O 0
a O 0
randomised O 0
study O 0
. O 0

Plasma O 0
potassium B-Chemical 0
concentrations O 0
were O 0
on O 0
average O 0
1 O 0
mmol O 0
/ O 0
L O 0
lower O 0
during O 0
the O 0
chlorthalidone B-Chemical 0
phase O 0
compared O 0
to O 0
amiloride B-Chemical 0
therapy O 0
. O 0

Blood O 0
pressure O 0
and O 0
volume O 0
states O 0
as O 0
assessed O 0
by O 0
bodyweight O 0
, O 0
plasma O 0
renin O 0
and O 0
noradrenaline B-Chemical 0
( O 0
norepinephrine B-Chemical 0
) O 0
concentrations O 0
were O 0
similar O 0
on O 0
the O 0
2 O 0
regimens O 0
. O 0

Compared O 0
to O 0
amiloride B-Chemical 0
treatment O 0
, O 0
the O 0
chlorthalidone B-Chemical 0
phase O 0
was O 0
associated O 0
with O 0
an O 0
increased O 0
frequency O 0
of O 0
ventricular B-Disease 0
ectopic I-Disease 0
beats I-Disease 0
( O 0
24 O 0
- O 0
hour O 0
Holter O 0
monitoring O 0
) O 0
and O 0
a O 0
higher O 0
Lown O 0
grading O 0
, O 0
increased O 0
upslope O 0
and O 0
duration O 0
of O 0
the O 0
monophasic O 0
action O 0
potential O 0
, O 0
prolonged O 0
ventricular O 0
effective O 0
refractory O 0
period O 0
, O 0
and O 0
increased O 0
electrical O 0
instability O 0
during O 0
programmed O 0
ventricular O 0
stimulation O 0
. O 0

The O 0
above O 0
results O 0
indicate O 0
that O 0
because O 0
potassium B-Chemical 0
- O 0
losing O 0
diuretic O 0
therapy O 0
can O 0
increase O 0
myocardial O 0
electrical O 0
excitability O 0
in O 0
patients O 0
with O 0
ischaemic B-Disease 0
heart I-Disease 0
disease I-Disease 0
, O 0
even O 0
minor O 0
falls O 0
in O 0
plasma O 0
potassium B-Chemical 0
concentrations O 0
are O 0
probably O 0
best O 0
avoided O 0
in O 0
such O 0
patients O 0
. O 0

Transketolase O 0
abnormality O 0
in O 0
tolazamide B-Chemical 0
- O 0
induced O 0
Wernicke B-Disease 0
' I-Disease 0
s I-Disease 0
encephalopathy I-Disease 0
. O 0

We O 0
studied O 0
a O 0
thiamine B-Chemical 0
- O 0
dependent O 0
enzyme O 0
, O 0
transketolase O 0
, O 0
from O 0
fibroblasts O 0
of O 0
a O 0
diabetic B-Disease 0
patient O 0
who O 0
developed O 0
Wernicke B-Disease 0
' I-Disease 0
s I-Disease 0
encephalopathy I-Disease 0
when O 0
treated O 0
with O 0
tolazamide B-Chemical 0
, O 0
in O 0
order O 0
to O 0
delineate O 0
if O 0
this O 0
patient O 0
also O 0
had O 0
transketolase O 0
abnormality O 0
[ O 0
high O 0
Km O 0
for O 0
thiamine B-Chemical 0
pyrophosphate I-Chemical 0
( O 0
TPP B-Chemical 0
) O 0
] O 0
, O 0
as O 0
previously O 0
reported O 0
in O 0
postalcoholic O 0
Wernicke B-Disease 0
- I-Disease 0
Korsakoff I-Disease 0
syndrome I-Disease 0
. O 0

In O 0
addition O 0
to O 0
this O 0
patient O 0
, O 0
we O 0
also O 0
studied O 0
this O 0
enzyme O 0
from O 0
three O 0
diabetic B-Disease 0
kindreds O 0
without O 0
any O 0
history O 0
of O 0
Wernicke B-Disease 0
' I-Disease 0
s I-Disease 0
encephalopathy I-Disease 0
and O 0
from O 0
four O 0
normal O 0
controls O 0
. O 0

We O 0
found O 0
that O 0
the O 0
above O 0
- O 0
mentioned O 0
patient O 0
and O 0
one O 0
of O 0
the O 0
diabetic B-Disease 0
kindreds O 0
with O 0
no O 0
history O 0
of O 0
Wernicke B-Disease 0
' I-Disease 0
s I-Disease 0
encephalopathy I-Disease 0
had O 0
abnormal O 0
transketolase O 0
as O 0
determined O 0
by O 0
its O 0
Km O 0
for O 0
TPP B-Chemical 0
. O 0

These O 0
data O 0
suggest O 0
a O 0
similarity O 0
between O 0
postalcoholic O 0
Wernicke B-Disease 0
- I-Disease 0
Korsakoff I-Disease 0
syndrome I-Disease 0
and O 0
the O 0
patient O 0
with O 0
tolazamide B-Chemical 0
- O 0
induced O 0
Wernicke B-Disease 0
' I-Disease 0
s I-Disease 0
encephalopathy I-Disease 0
from O 0
the O 0
standpoint O 0
of O 0
transketolase O 0
abnormality O 0
. O 0

Bradycardia B-Disease 0
due O 0
to O 0
trihexyphenidyl B-Chemical 0
hydrochloride I-Chemical 0
. O 0

A O 0
chronic O 0
schizophrenic B-Disease 0
patient O 0
was O 0
treated O 0
with O 0
an O 0
anticholinergic O 0
drug O 0
, O 0
trihexyphenidyl B-Chemical 0
hydrochloride I-Chemical 0
. O 0

The O 0
patient O 0
developed O 0
, O 0
paradoxically O 0
, O 0
sinus O 0
bradycardia B-Disease 0
. O 0

The O 0
reaction O 0
was O 0
specific O 0
to O 0
trihexyphenidyl B-Chemical 0
and O 0
not O 0
to O 0
other O 0
anticholinergic O 0
drugs O 0
. O 0

This O 0
antidyskinetic O 0
drug O 0
is O 0
widely O 0
used O 0
in O 0
clinical O 0
psychiatric B-Disease 0
practice O 0
and O 0
physicians O 0
should O 0
be O 0
aware O 0
of O 0
this O 0
side O 0
effect O 0
. O 0

Post O 0
- O 0
operative O 0
rigidity B-Disease 0
after O 0
fentanyl B-Chemical 0
administration O 0
. O 0

A O 0
case O 0
of O 0
thoraco O 0
- O 0
abdominal O 0
rigidity B-Disease 0
leading O 0
to O 0
respiratory B-Disease 0
failure I-Disease 0
is O 0
described O 0
in O 0
the O 0
post O 0
- O 0
operative O 0
period O 0
in O 0
an O 0
elderly O 0
patient O 0
who O 0
received O 0
a O 0
moderate O 0
dose O 0
of O 0
fentanyl B-Chemical 0
. O 0

This O 0
was O 0
successfully O 0
reversed O 0
by O 0
naloxone B-Chemical 0
. O 0

The O 0
mechanisms O 0
possibly O 0
implicated O 0
in O 0
this O 0
accident O 0
are O 0
discussed O 0
. O 0

Anti O 0
- O 0
carcinogenic B-Disease 0
action O 0
of O 0
phenobarbital B-Chemical 0
given O 0
simultaneously O 0
with O 0
diethylnitrosamine B-Chemical 0
in O 0
the O 0
rat O 0
. O 0

The O 0
present O 0
work O 0
has O 0
been O 0
planned O 0
in O 0
order O 0
to O 0
elucidate O 0
the O 0
effect O 0
of O 0
phenobarbital B-Chemical 0
( O 0
PB B-Chemical 0
: O 0
15 O 0
mg O 0
per O 0
rat O 0
of O 0
ingested O 0
dose O 0
) O 0
on O 0
carcinogenesis B-Disease 0
when O 0
it O 0
is O 0
administered O 0
simultaneously O 0
with O 0
diethylnitrosamine B-Chemical 0
( O 0
DEN B-Chemical 0
: O 0
10 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
) O 0
. O 0

Wistar O 0
rats O 0
( O 0
180 O 0
g O 0
) O 0
were O 0
treated O 0
by O 0
DEN B-Chemical 0
alone O 0
or O 0
by O 0
DEN B-Chemical 0
+ O 0
PB B-Chemical 0
during O 0
2 O 0
, O 0
4 O 0
and O 0
6 O 0
weeks O 0
according O 0
to O 0
our O 0
schedule O 0
for O 0
hepatocarcinogenesis B-Disease 0
. O 0

After O 0
the O 0
end O 0
of O 0
the O 0
treatment O 0
, O 0
the O 0
number O 0
and O 0
the O 0
size O 0
of O 0
induced O 0
PAS O 0
positive O 0
preneoplastic B-Disease 0
foci I-Disease 0
was O 0
significantly O 0
reduced O 0
when O 0
PB B-Chemical 0
was O 0
given O 0
simultaneously O 0
with O 0
DEN B-Chemical 0
for O 0
4 O 0
and O 0
6 O 0
weeks O 0
. O 0

The O 0
mitotic O 0
inhibition O 0
and O 0
the O 0
production O 0
of O 0
micronuclei O 0
normally O 0
observed O 0
after O 0
partial O 0
hepatectomy O 0
in O 0
DEN B-Chemical 0
treated O 0
rats O 0
were O 0
also O 0
significantly O 0
decreased O 0
in O 0
DEN B-Chemical 0
+ O 0
PB B-Chemical 0
treated O 0
rats O 0
. O 0

When O 0
the O 0
treatment O 0
last O 0
only O 0
2 O 0
weeks O 0
, O 0
the O 0
presence O 0
of O 0
PB B-Chemical 0
did O 0
not O 0
change O 0
significantly O 0
the O 0
last O 0
parameters O 0
. O 0

In O 0
DEN B-Chemical 0
+ O 0
PB B-Chemical 0
treated O 0
rats O 0
, O 0
the O 0
survival O 0
was O 0
prolonged O 0
and O 0
the O 0
tumor B-Disease 0
incidence O 0
decreased O 0
as O 0
compared O 0
with O 0
the O 0
results O 0
obtained O 0
by O 0
DEN B-Chemical 0
alone O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
PB B-Chemical 0
, O 0
which O 0
promotes O 0
carcinogenesis B-Disease 0
when O 0
administered O 0
after O 0
the O 0
DEN B-Chemical 0
treatment O 0
, O 0
reduces O 0
the O 0
carcinogen O 0
effect O 0
when O 0
given O 0
simultaneously O 0
with O 0
DEN B-Chemical 0
. O 0

This O 0
' O 0
anti O 0
- O 0
carcinogen O 0
' O 0
effect O 0
acts O 0
on O 0
the O 0
initiation O 0
as O 0
well O 0
as O 0
on O 0
the O 0
promotion O 0
of O 0
the O 0
precancerous B-Disease 0
lesions I-Disease 0
. O 0

Biochemical O 0
investigations O 0
are O 0
in O 0
progress O 0
to O 0
obtain O 0
more O 0
information O 0
about O 0
this O 0
' O 0
paradoxical O 0
' O 0
PB B-Chemical 0
effect O 0
. O 0

Bilateral B-Disease 0
optic I-Disease 0
neuropathy I-Disease 0
due O 0
to O 0
combined O 0
ethambutol B-Chemical 0
and O 0
isoniazid B-Chemical 0
treatment O 0
. O 0

The O 0
case O 0
of O 0
a O 0
40 O 0
- O 0
year O 0
- O 0
old O 0
patient O 0
who O 0
underwent O 0
an O 0
unsuccessful O 0
cadaver O 0
kidney O 0
transplantation O 0
and O 0
was O 0
treated O 0
with O 0
ethambutol B-Chemical 0
and O 0
isoniazid B-Chemical 0
is O 0
reported O 0
. O 0

A O 0
bilateral B-Disease 0
retrobulbar I-Disease 0
neuropathy I-Disease 0
with O 0
an O 0
unusual O 0
central O 0
bitemporal O 0
hemianopic O 0
scotoma B-Disease 0
was O 0
found O 0
. O 0

Ethambutol B-Chemical 0
was O 0
stopped O 0
and O 0
only O 0
small O 0
improvement O 0
of O 0
the O 0
visual O 0
acuity O 0
followed O 0
. O 0

Isoniazid B-Chemical 0
was O 0
discontinued O 0
later O 0
, O 0
followed O 0
by O 0
a O 0
dramatic O 0
improvement O 0
in O 0
the O 0
visual O 0
acuity O 0
. O 0

The O 0
hazards O 0
of O 0
optic O 0
nerve O 0
toxicity B-Disease 0
due O 0
to O 0
ethambutol B-Chemical 0
are O 0
known O 0
. O 0

We O 0
emphasize O 0
the O 0
potential O 0
danger O 0
in O 0
the O 0
use O 0
of O 0
ethambutol B-Chemical 0
and O 0
isoniazid B-Chemical 0
. O 0

A O 0
prospective O 0
study O 0
of O 0
adverse O 0
reactions O 0
associated O 0
with O 0
vancomycin B-Chemical 0
therapy O 0
. O 0

A O 0
prospective O 0
evaluation O 0
of O 0
the O 0
efficacy O 0
and O 0
safety O 0
of O 0
vancomycin B-Chemical 0
was O 0
conducted O 0
in O 0
54 O 0
consecutive O 0
patients O 0
over O 0
a O 0
16 O 0
- O 0
month O 0
period O 0
. O 0

Vancomycin B-Chemical 0
was O 0
curative O 0
in O 0
95 O 0
% O 0
of O 0
43 O 0
patients O 0
with O 0
proven O 0
infection B-Disease 0
. O 0

Drugs O 0
were O 0
ceased O 0
in O 0
six O 0
patients O 0
because O 0
of O 0
adverse O 0
reactions O 0
; O 0
in O 0
three O 0
of O 0
these O 0
vancomycin B-Chemical 0
was O 0
considered O 0
the O 0
likely O 0
cause O 0
. O 0

Reactions O 0
included O 0
thrombophlebitis B-Disease 0
( O 0
20 O 0
of O 0
54 O 0
patients O 0
) O 0
, O 0
rash B-Disease 0
( O 0
4 O 0
of O 0
54 O 0
) O 0
, O 0
nephrotoxicity B-Disease 0
( O 0
4 O 0
of O 0
50 O 0
) O 0
, O 0
proteinuria B-Disease 0
( O 0
1 O 0
of O 0
50 O 0
) O 0
and O 0
ototoxicity B-Disease 0
( O 0
1 O 0
of O 0
11 O 0
patients O 0
tested O 0
by O 0
audiometry O 0
) O 0
. O 0

Thrombophlebitis B-Disease 0
occurred O 0
only O 0
with O 0
infusion O 0
through O 0
peripheral O 0
cannulae O 0
; O 0
nephrotoxicity B-Disease 0
and O 0
ototoxicity B-Disease 0
were O 0
confined O 0
to O 0
patients O 0
receiving O 0
an O 0
aminoglycoside B-Chemical 0
plus O 0
vancomycin B-Chemical 0
. O 0

We O 0
conclude O 0
that O 0
vancomycin B-Chemical 0
, O 0
administered O 0
appropriately O 0
, O 0
constitutes O 0
safe O 0
, O 0
effective O 0
therapy O 0
for O 0
infections B-Disease 0
caused O 0
by O 0
susceptible O 0
bacteria O 0
. O 0

Factors O 0
associated O 0
with O 0
nephrotoxicity B-Disease 0
and O 0
clinical O 0
outcome O 0
in O 0
patients O 0
receiving O 0
amikacin B-Chemical 0
. O 0

Data O 0
from O 0
60 O 0
patients O 0
treated O 0
with O 0
amikacin B-Chemical 0
were O 0
analyzed O 0
for O 0
factors O 0
associated O 0
with O 0
nephrotoxicity B-Disease 0
. O 0

In O 0
42 O 0
of O 0
these O 0
patients O 0
, O 0
data O 0
were O 0
examined O 0
for O 0
factors O 0
associated O 0
with O 0
clinical O 0
outcome O 0
. O 0

Variables O 0
evaluated O 0
included O 0
patient O 0
weight O 0
, O 0
age O 0
, O 0
sex O 0
, O 0
serum O 0
creatinine B-Chemical 0
level O 0
, O 0
creatinine B-Chemical 0
clearance O 0
, O 0
duration O 0
of O 0
therapy O 0
, O 0
total O 0
dose O 0
, O 0
mean O 0
daily O 0
dose O 0
, O 0
organism O 0
minimum O 0
inhibitory O 0
concentration O 0
( O 0
MIC O 0
) O 0
, O 0
mean O 0
peak O 0
levels O 0
, O 0
mean O 0
trough O 0
levels O 0
, O 0
mean O 0
area O 0
under O 0
the O 0
serum O 0
concentration O 0
- O 0
time O 0
curve O 0
( O 0
AUC O 0
) O 0
, O 0
total O 0
AUC O 0
, O 0
mean O 0
AUC O 0
greater O 0
than O 0
MIC O 0
, O 0
total O 0
AUC O 0
greater O 0
than O 0
MIC O 0
, O 0
mean O 0
Schumacher O 0
' O 0
s O 0
intensity O 0
factor O 0
( O 0
IF O 0
) O 0
, O 0
total O 0
IF O 0
, O 0
In O 0
( O 0
mean O 0
maximum O 0
concentration O 0
[ O 0
Cmax O 0
] O 0
/ O 0
MIC O 0
) O 0
. O 0

Model O 0
- O 0
dependent O 0
pharmacokinetic O 0
parameters O 0
were O 0
calculated O 0
by O 0
computer O 0
based O 0
on O 0
a O 0
one O 0
- O 0
compartment O 0
model O 0
. O 0

When O 0
the O 0
parameters O 0
were O 0
examined O 0
individually O 0
, O 0
duration O 0
of O 0
therapy O 0
and O 0
total O 0
AUC O 0
correlated O 0
significantly O 0
( O 0
P O 0
less O 0
than O 0
. O 0
05 O 0
) O 0
with O 0
nephrotoxicity B-Disease 0
. O 0

In O 0
contrast O 0
, O 0
a O 0
stepwise O 0
discriminant O 0
function O 0
analysis O 0
identified O 0
only O 0
duration O 0
of O 0
therapy O 0
( O 0
P O 0
less O 0
than O 0
. O 0
001 O 0
) O 0
as O 0
an O 0
important O 0
factor O 0
. O 0

Based O 0
on O 0
this O 0
model O 0
and O 0
on O 0
Bayes O 0
' O 0
theorem O 0
, O 0
the O 0
predictive O 0
accuracy O 0
of O 0
identifying O 0
" O 0
nephrotoxic B-Disease 0
" O 0
patients O 0
increased O 0
from O 0
0 O 0
. O 0
17 O 0
to O 0
0 O 0
. O 0
39 O 0
. O 0

When O 0
examined O 0
individually O 0
, O 0
mean O 0
IF O 0
, O 0
MIC O 0
, O 0
total O 0
dose O 0
, O 0
mean O 0
daily O 0
dose O 0
, O 0
and O 0
ln O 0
( O 0
mean O 0
Cmax O 0
/ O 0
MIC O 0
) O 0
correlated O 0
significantly O 0
( O 0
P O 0
less O 0
than O 0
. O 0
05 O 0
) O 0
with O 0
cure O 0
. O 0

In O 0
contrast O 0
, O 0
a O 0
simultaneous O 0
multivariable O 0
analysis O 0
identified O 0
IF O 0
, O 0
MIC O 0
, O 0
and O 0
total O 0
dose O 0
according O 0
to O 0
one O 0
model O 0
and O 0
ln O 0
( O 0
mean O 0
Cmax O 0
/ O 0
MIC O 0
) O 0
according O 0
to O 0
a O 0
second O 0
statistical O 0
model O 0
of O 0
parameters O 0
selected O 0
to O 0
have O 0
the O 0
greatest O 0
prospective O 0
value O 0
. O 0

Based O 0
on O 0
Bayes O 0
' O 0
theorem O 0
and O 0
the O 0
first O 0
model O 0
, O 0
the O 0
predictive O 0
accuracy O 0
of O 0
identifying O 0
patients O 0
not O 0
cured O 0
increased O 0
from O 0
0 O 0
. O 0
19 O 0
to O 0
0 O 0
. O 0
83 O 0
. O 0

For O 0
the O 0
second O 0
model O 0
, O 0
the O 0
predictive O 0
accuracy O 0
increased O 0
from O 0
0 O 0
. O 0
19 O 0
to O 0
0 O 0
. O 0
50 O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Cardiac B-Disease 0
toxicity I-Disease 0
of O 0
5 B-Chemical 0
- I-Chemical 0
fluorouracil I-Chemical 0
. O 0

Report O 0
of O 0
a O 0
case O 0
of O 0
spontaneous O 0
angina B-Disease 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
a O 0
patient O 0
with O 0
colon B-Disease 0
carcinoma I-Disease 0
and O 0
liver O 0
metastasis B-Disease 0
who O 0
presented O 0
chest B-Disease 0
pain I-Disease 0
after 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
administration O 0
. O 0

Clinical O 0
electrocardiographic O 0
evolution O 0
was O 0
similar O 0
to O 0
that O 0
observed O 0
in O 0
Prinzmetal B-Disease 0
' I-Disease 0
s I-Disease 0
angina I-Disease 0
, O 0
and O 0
chest B-Disease 0
pain I-Disease 0
promptly O 0
resolved O 0
with O 0
nifedipine B-Chemical 0
. O 0

These O 0
data O 0
suggest O 0
that O 0
coronary B-Disease 0
spasm I-Disease 0
may O 0
be O 0
the O 0
cause O 0
of O 0
cardiotoxicity B-Disease 0
due O 0
to O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
, O 0
and O 0
that O 0
calcium B-Chemical 0
antagonists O 0
may O 0
probably O 0
be O 0
used O 0
in O 0
the O 0
prevention O 0
or O 0
treatment O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
FU I-Chemical 0
cardiotoxicity B-Disease 0
. O 0

Dose O 0
- O 0
related O 0
beneficial O 0
and O 0
adverse O 0
effects O 0
of O 0
dietary O 0
corticosterone B-Chemical 0
on O 0
organophosphorus B-Chemical 0
- O 0
induced O 0
delayed O 0
neuropathy B-Disease 0
in O 0
chickens O 0
. O 0

Tri B-Chemical 0
- I-Chemical 0
ortho I-Chemical 0
- I-Chemical 0
tolyl I-Chemical 0
phosphate I-Chemical 0
( O 0
TOTP B-Chemical 0
) O 0
, O 0
360 O 0
mg O 0
/ O 0
kg O 0
, O 0
po O 0
, O 0
and O 0
0 B-Chemical 0
, I-Chemical 0
0 I-Chemical 0
' I-Chemical 0
- I-Chemical 0
diisopropyl I-Chemical 0
phosphorofluoridate I-Chemical 0
( O 0
DFP B-Chemical 0
) O 0
, O 0
1 O 0
mg O 0
/ O 0
kg O 0
sc O 0
, O 0
were O 0
administered O 0
to O 0
adult O 0
White O 0
Leghorn O 0
chickens O 0
24 O 0
hr O 0
after O 0
they O 0
were O 0
placed O 0
on O 0
diets O 0
containing O 0
0 O 0
to O 0
300 O 0
ppm O 0
corticosterone B-Chemical 0
. O 0

Supplemented O 0
diets O 0
were O 0
continued O 0
until O 0
clinical O 0
signs O 0
and O 0
lesions O 0
of O 0
delayed O 0
neuropathy B-Disease 0
appeared O 0
. O 0

Although O 0
low O 0
concentrations O 0
( O 0
less O 0
than O 0
or O 0
equal O 0
to O 0
50 O 0
ppm O 0
) O 0
of O 0
corticosterone B-Chemical 0
had O 0
beneficial O 0
effects O 0
on O 0
TOTP B-Chemical 0
- O 0
induced O 0
neuropathy B-Disease 0
, O 0
greater O 0
than O 0
or O 0
equal O 0
to O 0
200 O 0
ppm O 0
exacerbated O 0
clinical O 0
signs O 0
in O 0
chickens O 0
given O 0
either O 0
TOTP B-Chemical 0
or O 0
DFP B-Chemical 0
. O 0

Neurotoxic B-Disease 0
esterase O 0
activities O 0
24 O 0
hr O 0
after O 0
TOTP B-Chemical 0
or O 0
DFP B-Chemical 0
were O 0
less O 0
than O 0
20 O 0
% O 0
of O 0
values O 0
measured O 0
in O 0
chickens O 0
not O 0
given O 0
organophosphorous B-Chemical 0
compounds O 0
. O 0

Chickens O 0
given O 0
200 O 0
ppm O 0
corticosterone B-Chemical 0
without O 0
TOTP B-Chemical 0
or O 0
DFP B-Chemical 0
had O 0
significantly O 0
elevated O 0
activity O 0
of O 0
plasma O 0
cholinesterase O 0
and O 0
significantly O 0
inhibited O 0
activity O 0
of O 0
liver O 0
carboxylesterase O 0
. O 0

Degenerating B-Disease 0
myelinated I-Disease 0
fibers I-Disease 0
were O 0
also O 0
evident O 0
in O 0
distal O 0
levels O 0
of O 0
the O 0
peripheral O 0
nerves O 0
of O 0
chickens O 0
given O 0
TOTP B-Chemical 0
or O 0
DFP B-Chemical 0
. O 0

Hepatotoxicity B-Disease 0
of O 0
amiodarone B-Chemical 0
. O 0

Amiodarone B-Chemical 0
has O 0
proved O 0
very O 0
effective O 0
in O 0
the O 0
treatment O 0
of O 0
otherwise O 0
resistant O 0
cardiac O 0
tachyarrhythmias B-Disease 0
. O 0

The O 0
use O 0
of O 0
amiodarone B-Chemical 0
has O 0
, O 0
however O 0
, O 0
been O 0
limited O 0
due O 0
to O 0
its O 0
serious O 0
side O 0
- O 0
effects O 0
. O 0

A O 0
patient O 0
with O 0
cholestatic B-Disease 0
hepatitis I-Disease 0
due O 0
to O 0
amiodarone B-Chemical 0
treatment O 0
is O 0
presented O 0
below O 0
and O 0
a O 0
review O 0
of O 0
the O 0
hepatotoxicity B-Disease 0
of O 0
amiodarone B-Chemical 0
is O 0
given O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
solid O 0
evidence O 0
exists O 0
of O 0
hepatic B-Disease 0
injury I-Disease 0
due O 0
to O 0
amiodarone B-Chemical 0
treatment O 0
, O 0
including O 0
steatosis B-Disease 0
, O 0
alterations O 0
resembling O 0
alcoholic B-Disease 0
hepatitis I-Disease 0
, O 0
cholestatic B-Disease 0
hepatitis I-Disease 0
and O 0
micronodular O 0
cirrhosis B-Disease 0
of I-Disease 0
the I-Disease 0
liver I-Disease 0
. O 0

Patients O 0
receiving O 0
amiodarone B-Chemical 0
should O 0
be O 0
regularly O 0
screened O 0
with O 0
respect O 0
to O 0
hepatic O 0
enzyme O 0
levels O 0
. O 0

Therapy O 0
should O 0
be O 0
discontinued O 0
on O 0
the O 0
suspicion O 0
of O 0
cholestatic B-Disease 0
injury I-Disease 0
or O 0
hepatomegaly B-Disease 0
. O 0

Promotional O 0
effects O 0
of O 0
testosterone B-Chemical 0
and O 0
dietary O 0
fat O 0
on O 0
prostate O 0
carcinogenesis B-Disease 0
in O 0
genetically O 0
susceptible O 0
rats O 0
. O 0

Germfree O 0
( O 0
GF O 0
) O 0
Lobund O 0
strain O 0
Wistar O 0
( O 0
LW O 0
) O 0
rats O 0
, O 0
fed O 0
vegetable O 0
diet O 0
L O 0
- O 0
485 O 0
, O 0
have O 0
developed O 0
prostate B-Disease 0
adenocarcinomas I-Disease 0
spontaneously O 0
( O 0
10 O 0
% O 0
incidence O 0
) O 0
at O 0
average O 0
age O 0
34 O 0
months O 0
. O 0

Conventional O 0
LW O 0
rats O 0
, O 0
implanted O 0
with O 0
testosterone B-Chemical 0
at O 0
age O 0
4 O 0
months O 0
, O 0
developed O 0
a O 0
higher O 0
incidence O 0
of O 0
prostate B-Disease 0
cancer I-Disease 0
after O 0
an O 0
average O 0
interval O 0
of O 0
14 O 0
months O 0
: O 0
24 O 0
% O 0
had O 0
developed O 0
gross O 0
tumors B-Disease 0
, O 0
and O 0
40 O 0
% O 0
when O 0
it O 0
included O 0
microscopic O 0
tumors B-Disease 0
. O 0

Preliminary O 0
results O 0
indicate O 0
that O 0
testosterone B-Chemical 0
- O 0
treated O 0
LW O 0
rats O 0
that O 0
were O 0
fed O 0
the O 0
same O 0
diet O 0
, O 0
which O 0
was O 0
supplemented O 0
with O 0
corn O 0
oil O 0
up O 0
to O 0
20 O 0
% O 0
fat O 0
, O 0
developed O 0
prostate B-Disease 0
cancer I-Disease 0
after O 0
intervals O 0
of O 0
6 O 0
- O 0
12 O 0
months O 0
. O 0

Aged O 0
GF O 0
Sprague O 0
- O 0
Dawley O 0
( O 0
SD O 0
) O 0
rats O 0
have O 0
not O 0
developed O 0
prostate B-Disease 0
cancer I-Disease 0
spontaneously O 0
. O 0

Conventional O 0
SD O 0
rats O 0
fed O 0
diet O 0
L O 0
- O 0
485 O 0
and O 0
treated O 0
with O 0
testosterone B-Chemical 0
developed O 0
only O 0
prostatitis B-Disease 0
. O 0

Experimental O 0
designs O 0
should O 0
consider O 0
genetic O 0
susceptibility O 0
as O 0
a O 0
basic O 0
prerequisite O 0
for O 0
studies O 0
on O 0
experimental O 0
prostate B-Disease 0
cancer I-Disease 0
. O 0

Time O 0
course O 0
alterations O 0
of O 0
QTC O 0
interval O 0
due O 0
to O 0
hypaque B-Chemical 0
76 I-Chemical 0
. O 0

Sequential O 0
measurement O 0
of O 0
QT O 0
interval O 0
during O 0
left O 0
ventricular O 0
angiography O 0
was O 0
made O 0
30 O 0
seconds O 0
and O 0
one O 0
, O 0
three O 0
, O 0
five O 0
and O 0
ten O 0
minutes O 0
after O 0
injection O 0
of O 0
hypaque B-Chemical 0
76 I-Chemical 0
. O 0

The O 0
subjects O 0
were O 0
ten O 0
patients O 0
found O 0
to O 0
have O 0
normal O 0
left O 0
ventricles O 0
and O 0
coronary O 0
arteries O 0
. O 0

Significant O 0
QTC B-Disease 0
prolongation I-Disease 0
occurred O 0
in O 0
30 O 0
seconds O 0
to O 0
one O 0
minute O 0
in O 0
association O 0
with O 0
marked O 0
hypotension B-Disease 0
and O 0
elevation O 0
of O 0
cardiac O 0
output O 0
. O 0

Rat O 0
extraocular O 0
muscle O 0
regeneration O 0
. O 0

Repair O 0
of O 0
local O 0
anesthetic O 0
- O 0
induced O 0
damage O 0
. O 0

Local O 0
anesthetics O 0
that O 0
are O 0
commonly O 0
used O 0
in O 0
ophthalmic O 0
surgery O 0
( O 0
0 O 0
. O 0
75 O 0
% O 0
bupivacaine B-Chemical 0
hydrochloride I-Chemical 0
, O 0
2 O 0
. O 0
0 O 0
% O 0
mepivacaine B-Chemical 0
hydrochloride I-Chemical 0
, O 0
and O 0
2 O 0
. O 0
0 O 0
% O 0
lidocaine B-Chemical 0
hydrochloride I-Chemical 0
plus O 0
1 O 0
: O 0
100 O 0
, O 0
000 O 0
epinephrine B-Chemical 0
) O 0
were O 0
injected O 0
into O 0
the O 0
retrobulbar O 0
area O 0
of O 0
rat O 0
eyes O 0
. O 0

Controls O 0
were O 0
injected O 0
with O 0
physiological O 0
saline O 0
. O 0

All O 0
three O 0
anesthetics O 0
produced O 0
massive O 0
degeneration O 0
of O 0
the O 0
extraocular O 0
muscles O 0
. O 0

Muscle B-Disease 0
degeneration I-Disease 0
is O 0
followed O 0
by O 0
regeneration O 0
of O 0
the O 0
damaged O 0
muscle O 0
fibers O 0
. O 0

In O 0
addition O 0
to O 0
muscle B-Disease 0
damage I-Disease 0
, O 0
severe O 0
damage O 0
was O 0
also O 0
seen O 0
in O 0
harderian O 0
glands O 0
, O 0
especially O 0
after O 0
exposure O 0
to O 0
mepivacaine B-Chemical 0
and O 0
lidocaine B-Chemical 0
plus O 0
epinephrine B-Chemical 0
. O 0

With O 0
these O 0
findings O 0
in O 0
rats O 0
, O 0
it O 0
is O 0
hypothesized O 0
that O 0
the O 0
temporary O 0
diplopia B-Disease 0
sometimes O 0
seen O 0
in O 0
patients O 0
after O 0
ophthalmic O 0
surgery O 0
might O 0
be O 0
due O 0
to O 0
anesthetic O 0
- O 0
induced O 0
damage O 0
to O 0
the O 0
extraocular O 0
muscles O 0
. O 0

Gentamicin B-Chemical 0
nephropathy B-Disease 0
in O 0
a O 0
neonate O 0
. O 0

The O 0
clinical O 0
and O 0
autopsy O 0
findings O 0
in O 0
a O 0
premature O 0
baby O 0
who O 0
died O 0
of O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
after O 0
therapy O 0
with O 0
gentamicin B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
) O 0
and O 0
penicillin B-Chemical 0
are O 0
presented O 0
. O 0

The O 0
serum O 0
gentamicin B-Chemical 0
concentration O 0
had O 0
reached O 0
toxic O 0
levels O 0
when O 0
anuria B-Disease 0
developed O 0
. O 0

Numerous O 0
periodic B-Chemical 0
acid I-Chemical 0
Schiff O 0
( O 0
PAS O 0
) O 0
positive O 0
, O 0
diastase O 0
resistant O 0
cytoplasmic O 0
inclusion O 0
bodies O 0
which O 0
appeared O 0
as O 0
myelin O 0
figures O 0
in O 0
cytosegresomes O 0
under O 0
the O 0
electron O 0
microscope O 0
were O 0
identified O 0
in O 0
the O 0
proximal O 0
convoluted O 0
tubules O 0
. O 0

The O 0
pathological O 0
changes O 0
induced O 0
by O 0
gentamicin B-Chemical 0
in O 0
the O 0
human O 0
neonatal O 0
kidneys O 0
have O 0
not O 0
been O 0
previously O 0
reported O 0
. O 0

Induction O 0
by O 0
paracetamol B-Chemical 0
of O 0
bladder B-Disease 0
and I-Disease 0
liver I-Disease 0
tumours I-Disease 0
in O 0
the O 0
rat O 0
. O 0

Effects O 0
on O 0
hepatocyte O 0
fine O 0
structure O 0
. O 0

Groups O 0
of O 0
male O 0
and O 0
female O 0
inbred O 0
Leeds O 0
strain O 0
rats O 0
were O 0
fed O 0
diets O 0
containing O 0
either O 0
0 O 0
. O 0
5 O 0
% O 0
or O 0
1 O 0
. O 0
0 O 0
% O 0
paracetamol B-Chemical 0
by O 0
weight O 0
for O 0
up O 0
to O 0
18 O 0
months O 0
. O 0

At O 0
the O 0
1 O 0
. O 0
0 O 0
% O 0
dosage O 0
level O 0
, O 0
20 O 0
% O 0
of O 0
rats O 0
of O 0
both O 0
sexes O 0
developed O 0
neoplastic O 0
nodules O 0
of O 0
the O 0
liver O 0
, O 0
a O 0
statistically O 0
significant O 0
incidence O 0
. O 0

These O 0
rats O 0
also O 0
showed O 0
gross O 0
enlargement O 0
of O 0
their O 0
livers O 0
and O 0
an O 0
increase O 0
in O 0
foci O 0
of O 0
cellular O 0
alteration O 0
, O 0
the O 0
latter O 0
also O 0
being O 0
observed O 0
in O 0
the O 0
low O 0
dosage O 0
male O 0
rats O 0
. O 0

Papillomas B-Disease 0
of O 0
the O 0
transitional O 0
epithelium O 0
of O 0
the O 0
bladder O 0
developed O 0
in O 0
all O 0
paracetamol B-Chemical 0
- O 0
treated O 0
groups O 0
, O 0
and O 0
three O 0
rats O 0
bore O 0
bladder B-Disease 0
carcinomas I-Disease 0
. O 0

However O 0
, O 0
significant O 0
yields O 0
of O 0
bladder B-Disease 0
tumours I-Disease 0
were O 0
only O 0
obtained O 0
from O 0
low O 0
dosage O 0
females O 0
and O 0
high O 0
dosage O 0
males O 0
. O 0

Additionally O 0
, O 0
20 O 0
to O 0
25 O 0
% O 0
of O 0
paracetamol B-Chemical 0
- O 0
treated O 0
rats O 0
developed O 0
hyperplasia B-Disease 0
of O 0
the O 0
bladder O 0
epithelium O 0
, O 0
which O 0
was O 0
not O 0
coincident O 0
with O 0
the O 0
presence O 0
of O 0
bladder B-Disease 0
calculi I-Disease 0
. O 0

A O 0
low O 0
yield O 0
of O 0
tumours B-Disease 0
at O 0
various O 0
other O 0
sites O 0
also O 0
arose O 0
following O 0
paracetamol B-Chemical 0
feeding O 0
. O 0

An O 0
electron O 0
microscope O 0
study O 0
of O 0
the O 0
livers O 0
of O 0
paracetamol B-Chemical 0
- O 0
treated O 0
rats O 0
revealed O 0
ultrastructural O 0
changes O 0
in O 0
the O 0
hepatocytes O 0
that O 0
resemble O 0
those O 0
that O 0
result O 0
from O 0
exposure O 0
to O 0
a O 0
variety O 0
of O 0
known O 0
hepatocarcinogens B-Disease 0
. O 0

Transient O 0
hemiparesis B-Disease 0
: O 0
a O 0
rare O 0
manifestation O 0
of O 0
diphenylhydantoin B-Chemical 0
toxicity B-Disease 0
. O 0

Report O 0
of O 0
two O 0
cases O 0
. O 0

Among O 0
the O 0
common O 0
side O 0
effects O 0
of O 0
diphenylhydantoin B-Chemical 0
( O 0
DPH B-Chemical 0
) O 0
overdose B-Disease 0
, O 0
the O 0
most O 0
frequently O 0
encountered O 0
neurological O 0
signs O 0
are O 0
those O 0
of O 0
cerebellar B-Disease 0
dysfunction I-Disease 0
. O 0

Very O 0
rarely O 0
, O 0
the O 0
toxic O 0
neurological O 0
manifestations O 0
of O 0
this O 0
drug O 0
are O 0
of O 0
cerebral O 0
origin O 0
. O 0

Two O 0
patients O 0
are O 0
presented O 0
who O 0
suffered O 0
progressive O 0
hemiparesis B-Disease 0
due O 0
to O 0
DPH B-Chemical 0
overdose B-Disease 0
. O 0

Both O 0
had O 0
brain O 0
surgery O 0
before O 0
DPH B-Chemical 0
treatment O 0
. O 0

It O 0
is O 0
assumed O 0
that O 0
patients O 0
with O 0
some O 0
cerebral B-Disease 0
damage I-Disease 0
are O 0
liable O 0
to O 0
manifest O 0
DPH B-Chemical 0
toxicity B-Disease 0
as O 0
focal O 0
neurological O 0
signs O 0
. O 0

Tiapride B-Chemical 0
in O 0
levodopa B-Chemical 0
- O 0
induced O 0
involuntary B-Disease 0
movements I-Disease 0
. O 0

Tiapride B-Chemical 0
, O 0
a O 0
substituted O 0
benzamide B-Chemical 0
derivative O 0
closely O 0
related O 0
to O 0
metoclopramide B-Chemical 0
, O 0
reduced O 0
levodopa B-Chemical 0
- O 0
induced O 0
peak O 0
dose O 0
involuntary B-Disease 0
movements I-Disease 0
in O 0
16 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
. O 0

However O 0
, O 0
an O 0
unacceptable O 0
increase O 0
in O 0
disability O 0
from O 0
Parkinsonism B-Disease 0
with O 0
aggravation O 0
of O 0
end O 0
- O 0
of O 0
- O 0
dose O 0
akinesia B-Disease 0
led O 0
to O 0
its O 0
cessation O 0
in O 0
14 O 0
patients O 0
. O 0

Tiapride B-Chemical 0
had O 0
no O 0
effect O 0
on O 0
levodopa B-Chemical 0
- O 0
induced O 0
early O 0
morning O 0
of O 0
" O 0
off O 0
- O 0
period O 0
" O 0
segmental O 0
dystonia B-Disease 0
. O 0

These O 0
results O 0
fail O 0
to O 0
support O 0
the O 0
notion O 0
that O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
are O 0
caused O 0
by O 0
overstimulation O 0
of O 0
a O 0
separate O 0
group O 0
of O 0
dopamine B-Chemical 0
receptors O 0
. O 0

Quinidine B-Chemical 0
hepatitis B-Disease 0
. O 0

Long O 0
- O 0
term O 0
administration O 0
of O 0
quinidine B-Chemical 0
was O 0
associated O 0
with O 0
persistent O 0
elevation O 0
of O 0
serum O 0
concentrations O 0
of O 0
SGOT O 0
, O 0
lactic B-Chemical 0
acid I-Chemical 0
dehydrogenase O 0
, O 0
and O 0
alkaline O 0
phosphatase O 0
. O 0

Liver O 0
biopsy O 0
showed O 0
active O 0
hepatitis B-Disease 0
. O 0

Discontinuance O 0
of O 0
quinidine B-Chemical 0
therapy O 0
led O 0
to O 0
normalization O 0
of O 0
liver O 0
function O 0
tests O 0
. O 0

A O 0
challenge O 0
dose O 0
of O 0
quinidine B-Chemical 0
caused O 0
clinical O 0
symptoms O 0
and O 0
abrupt O 0
elevation O 0
of O 0
SGOT O 0
, O 0
alkaline O 0
phosphatase O 0
, O 0
and O 0
lactic B-Chemical 0
acid I-Chemical 0
dehydrogenase O 0
values O 0
. O 0

We O 0
concluded O 0
that O 0
this O 0
patient O 0
had O 0
quinidine B-Chemical 0
hepatotoxicity B-Disease 0
and O 0
believe O 0
that O 0
this O 0
is O 0
the O 0
first O 0
case O 0
reported O 0
with O 0
liver O 0
biopsy O 0
documentation O 0
. O 0

This O 0
report O 0
also O 0
suggests O 0
that O 0
, O 0
even O 0
after O 0
long O 0
- O 0
term O 0
administration O 0
, O 0
the O 0
hepatic B-Disease 0
toxicity I-Disease 0
is O 0
reversible O 0
. O 0

Arterial O 0
thromboembolism B-Disease 0
in O 0
patients O 0
receiving O 0
systemic O 0
heparin B-Chemical 0
therapy O 0
: O 0
a O 0
complication O 0
associated O 0
with O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
. O 0

Arterial O 0
thromboembolism B-Disease 0
is O 0
a O 0
recognized O 0
complication O 0
of O 0
systemic O 0
heparin B-Chemical 0
therapy O 0
. O 0

Characteristic O 0
of O 0
the O 0
entity O 0
is O 0
arterial B-Disease 0
occlusion I-Disease 0
by O 0
platelet O 0
- O 0
fibrin O 0
thrombi B-Disease 0
with O 0
distal O 0
ischemia B-Disease 0
occurring O 0
four O 0
to O 0
twenty O 0
days O 0
after O 0
the O 0
initiation O 0
of O 0
heparin B-Chemical 0
therapy O 0
, O 0
preceded O 0
by O 0
profound O 0
thrombocytopenia B-Disease 0
with O 0
platelet O 0
counts O 0
in O 0
the O 0
range O 0
of O 0
30 O 0
, O 0
000 O 0
to O 0
40 O 0
, O 0
000 O 0
per O 0
cubic O 0
millimeter O 0
. O 0

The O 0
clinically O 0
apparent O 0
occlusion O 0
may O 0
be O 0
preceded O 0
by O 0
gastrointestinal B-Disease 0
and I-Disease 0
musculoskeletal I-Disease 0
symptoms I-Disease 0
that O 0
appear O 0
to O 0
be O 0
ischemic B-Disease 0
in O 0
origin O 0
, O 0
and O 0
might O 0
serve O 0
to O 0
warn O 0
the O 0
clinician O 0
of O 0
these O 0
complications O 0
. O 0

Previous O 0
reports O 0
of O 0
these O 0
phenomena O 0
as O 0
well O 0
as O 0
recent O 0
studies O 0
of O 0
the O 0
effect O 0
of O 0
heparin B-Chemical 0
are O 0
reviewed O 0
. O 0

The O 0
common O 0
factor O 0
relating O 0
thromboembolism B-Disease 0
and O 0
thrombocytopenia B-Disease 0
is O 0
heparin B-Chemical 0
- O 0
induced O 0
platelet B-Disease 0
aggregation I-Disease 0
. O 0

Appropriate O 0
treatment O 0
consists O 0
of O 0
discontinuation O 0
of O 0
heparin B-Chemical 0
, O 0
and O 0
anticoagulation O 0
with O 0
sodium B-Chemical 0
warfarin I-Chemical 0
if O 0
necessary O 0
. O 0

Vascular O 0
procedures O 0
are O 0
performed O 0
as O 0
indicated O 0
. O 0

Pharmacology O 0
of O 0
GYKI B-Chemical 0
- I-Chemical 0
41 I-Chemical 0
099 I-Chemical 0
( O 0
chlorpropanol B-Chemical 0
, O 0
Tobanum B-Chemical 0
) O 0
a O 0
new O 0
potent O 0
beta O 0
- O 0
adrenergic O 0
antagonist O 0
. O 0

The O 0
compound O 0
GYKI B-Chemical 0
- I-Chemical 0
41 I-Chemical 0
099 I-Chemical 0
, O 0
as O 0
a O 0
beta O 0
- O 0
adrenergic O 0
antagonist O 0
, O 0
is O 0
3 O 0
- O 0
8 O 0
times O 0
more O 0
potent O 0
than O 0
propranolol B-Chemical 0
in O 0
vitro O 0
and O 0
in O 0
vivo O 0
. O 0

Its O 0
antiarrhythmic O 0
effectiveness O 0
surpasses O 0
that O 0
of O 0
propranolol B-Chemical 0
and O 0
pindolol B-Chemical 0
inhibiting O 0
the O 0
ouabain B-Chemical 0
arrhythmia B-Disease 0
in O 0
dogs O 0
and O 0
cats O 0
. O 0

GYKI B-Chemical 0
- I-Chemical 0
41 I-Chemical 0
900 I-Chemical 0
has O 0
a O 0
negligible O 0
cardiodepressant O 0
activity O 0
; O 0
it O 0
is O 0
not O 0
cardioselective O 0
. O 0

The O 0
compound O 0
shows O 0
a O 0
rapid O 0
and O 0
long O 0
lasting O 0
effect O 0
. O 0

There O 0
was O 0
a O 0
prolonged O 0
elimination O 0
of O 0
the O 0
radioactivity O 0
after O 0
the O 0
injection O 0
of O 0
14C B-Chemical 0
- I-Chemical 0
41 I-Chemical 0
099 I-Chemical 0
to O 0
rats O 0
and O 0
dogs O 0
. O 0

The O 0
half O 0
life O 0
of O 0
the O 0
unlabeled O 0
substance O 0
in O 0
humans O 0
was O 0
more O 0
than O 0
10 O 0
hours O 0
. O 0

Adverse O 0
reactions O 0
to O 0
bendrofluazide B-Chemical 0
and O 0
propranolol B-Chemical 0
for O 0
the O 0
treatment O 0
of O 0
mild O 0
hypertension B-Disease 0
. O 0

Report O 0
of O 0
Medical O 0
Research O 0
Council O 0
Working O 0
Party O 0
on O 0
Mild O 0
to O 0
Moderate O 0
Hypertension B-Disease 0
. O 0

Participants O 0
in O 0
the O 0
Medical O 0
Research O 0
Council O 0
treatment O 0
trial O 0
for O 0
mild O 0
hypertension B-Disease 0
are O 0
randomly O 0
allocated O 0
to O 0
one O 0
of O 0
four O 0
treatment O 0
groups O 0
: O 0
bendrofluazide B-Chemical 0
, O 0
propranolol B-Chemical 0
, O 0
or O 0
a O 0
placebo O 0
for O 0
either O 0
of O 0
these O 0
drugs O 0
. O 0

The O 0
trial O 0
is O 0
single O 0
- O 0
blind O 0
. O 0

23 O 0
582 O 0
patient O 0
- O 0
years O 0
of O 0
observation O 0
have O 0
been O 0
completed O 0
so O 0
far O 0
, O 0
10 O 0
684 O 0
on O 0
active O 0
drugs O 0
and O 0
12 O 0
898 O 0
on O 0
placebos O 0
. O 0

The O 0
results O 0
show O 0
an O 0
association O 0
between O 0
bendrofluazide B-Chemical 0
treatment O 0
and O 0
impotence B-Disease 0
, O 0
and O 0
impotence B-Disease 0
also O 0
occurred O 0
more O 0
frequently O 0
in O 0
patients O 0
taking O 0
propranolol B-Chemical 0
than O 0
in O 0
those O 0
taking O 0
placebos O 0
. O 0

Other O 0
adverse O 0
reactions O 0
significantly O 0
linked O 0
with O 0
active O 0
drugs O 0
include O 0
impaired B-Disease 0
glucose I-Disease 0
tolerance I-Disease 0
in O 0
men O 0
and O 0
women O 0
and O 0
gout B-Disease 0
in O 0
men O 0
, O 0
associated O 0
with O 0
bendrofluazide B-Chemical 0
treatment O 0
, O 0
and O 0
Raynaud B-Disease 0
' I-Disease 0
s I-Disease 0
phenomenon I-Disease 0
and O 0
dyspnoea B-Disease 0
in O 0
men O 0
and O 0
women O 0
taking O 0
propranolol B-Chemical 0
. O 0

No O 0
corneal B-Disease 0
disease I-Disease 0
is O 0
known O 0
to O 0
have O 0
occurred O 0
in O 0
the O 0
propranolol B-Chemical 0
group O 0
. O 0

Mean O 0
serum O 0
potassium B-Chemical 0
level O 0
fell O 0
, O 0
and O 0
urea B-Chemical 0
and O 0
uric B-Chemical 0
acid I-Chemical 0
levels O 0
rose O 0
, O 0
in O 0
men O 0
and O 0
women O 0
taking O 0
bendrofluazide B-Chemical 0
. O 0

In O 0
the O 0
propranolol B-Chemical 0
group O 0
, O 0
serum O 0
potassium B-Chemical 0
and O 0
uric B-Chemical 0
acid I-Chemical 0
levels O 0
rose O 0
in O 0
both O 0
sexes O 0
, O 0
but O 0
the O 0
urea B-Chemical 0
level O 0
rose O 0
significantly O 0
in O 0
women O 0
only O 0
. O 0

Serotonergic O 0
drugs O 0
, O 0
benzodiazepines B-Chemical 0
and O 0
baclofen B-Chemical 0
block O 0
muscimol B-Chemical 0
- O 0
induced O 0
myoclonic B-Disease 0
jerks I-Disease 0
in O 0
a O 0
strain O 0
of O 0
mice O 0
. O 0

In O 0
male O 0
Swiss O 0
mice O 0
, O 0
muscimol B-Chemical 0
produced O 0
myoclonic B-Disease 0
jerks I-Disease 0
. O 0

A O 0
3 O 0
mg O 0
/ O 0
kg O 0
( O 0
i O 0
. O 0
p O 0
. O 0
) O 0
dose O 0
induced O 0
this O 0
response O 0
in O 0
all O 0
of O 0
the O 0
mice O 0
tested O 0
and O 0
the O 0
peak O 0
response O 0
of O 0
73 O 0
jerks O 0
per O 0
min O 0
was O 0
observed O 0
between O 0
27 O 0
and O 0
45 O 0
min O 0
. O 0

Increasing O 0
the O 0
brain O 0
serotonin B-Chemical 0
levels O 0
by O 0
the O 0
administration O 0
of O 0
5 B-Chemical 0
- I-Chemical 0
hydroxytryptophan I-Chemical 0
( O 0
80 O 0
- O 0
160 O 0
mg O 0
/ O 0
kg O 0
) O 0
in O 0
combination O 0
with O 0
a O 0
peripheral O 0
decarboxylase O 0
inhibitor O 0
resulted O 0
in O 0
an O 0
inhibition O 0
of O 0
the O 0
muscimol B-Chemical 0
effect O 0
. O 0

However O 0
, O 0
in O 0
a O 0
similar O 0
experiment O 0
l B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
( O 0
80 O 0
- O 0
160 O 0
mg O 0
/ O 0
kg O 0
) O 0
was O 0
without O 0
effect O 0
. O 0

In O 0
doses O 0
of O 0
3 O 0
- O 0
10 O 0
mg O 0
/ O 0
kg O 0
, O 0
the O 0
serotonin B-Chemical 0
receptor O 0
agonist O 0
MK B-Chemical 0
- I-Chemical 0
212 I-Chemical 0
caused O 0
a O 0
dose O 0
- O 0
dependent O 0
blockade O 0
of O 0
the O 0
response O 0
of O 0
muscimol B-Chemical 0
. O 0

Of O 0
the O 0
benzodiazepines B-Chemical 0
, O 0
clonazepam B-Chemical 0
( O 0
0 O 0
. O 0
1 O 0
- O 0
0 O 0
. O 0
3 O 0
mg O 0
/ O 0
kg O 0
) O 0
was O 0
found O 0
to O 0
be O 0
several O 0
fold O 0
more O 0
potent O 0
than O 0
diazepam B-Chemical 0
( O 0
0 O 0
. O 0
3 O 0
- O 0
3 O 0
mg O 0
/ O 0
kg O 0
) O 0
in O 0
blocking O 0
the O 0
myoclonic B-Disease 0
jerks I-Disease 0
. O 0

While O 0
( O 0
- O 0
) O 0
- O 0
baclofen B-Chemical 0
( O 0
1 O 0
- O 0
3 O 0
mg O 0
/ O 0
kg O 0
) O 0
proved O 0
to O 0
be O 0
an O 0
effective O 0
antagonist O 0
of O 0
muscimol B-Chemical 0
, O 0
its O 0
( O 0
+ O 0
) O 0
- O 0
isomer O 0
( O 0
5 O 0
- O 0
20 O 0
mg O 0
/ O 0
kg O 0
) O 0
lacked O 0
this O 0
property O 0
. O 0

Considering O 0
the O 0
fact O 0
that O 0
5 B-Chemical 0
- I-Chemical 0
HTP I-Chemical 0
and O 0
the O 0
benzodiazepines B-Chemical 0
have O 0
been O 0
found O 0
to O 0
be O 0
beneficial O 0
in O 0
the O 0
management O 0
of O 0
clinical O 0
myoclonus B-Disease 0
, O 0
the O 0
muscimol B-Chemical 0
- O 0
induced O 0
myoclonus B-Disease 0
seems O 0
to O 0
be O 0
a O 0
satisfactory O 0
animal O 0
model O 0
that O 0
may O 0
prove O 0
useful O 0
for O 0
the O 0
development O 0
of O 0
new O 0
drug O 0
treatments O 0
for O 0
this O 0
condition O 0
. O 0

Our O 0
present O 0
study O 0
indicated O 0
the O 0
possible O 0
value O 0
of O 0
MK B-Chemical 0
- I-Chemical 0
212 I-Chemical 0
and O 0
( O 0
- O 0
) O 0
- O 0
baclofen B-Chemical 0
in O 0
the O 0
management O 0
of O 0
clinical O 0
myoclonus B-Disease 0
. O 0

Adverse O 0
interaction O 0
between O 0
beta B-Chemical 0
- I-Chemical 0
adrenergic I-Chemical 0
blocking I-Chemical 0
drugs I-Chemical 0
and O 0
verapamil B-Chemical 0
- O 0
- O 0
report O 0
of O 0
three O 0
cases O 0
. O 0

Three O 0
patients O 0
with O 0
ischaemic B-Disease 0
heart I-Disease 0
disease I-Disease 0
developed O 0
profound O 0
cardiac B-Disease 0
failure I-Disease 0
, O 0
hypotension B-Disease 0
and O 0
bradycardia B-Disease 0
during O 0
combined O 0
therapy O 0
with O 0
verapamil B-Chemical 0
and O 0
beta B-Chemical 0
- I-Chemical 0
adrenergic I-Chemical 0
blocking I-Chemical 0
drugs I-Chemical 0
. O 0

This O 0
clinical O 0
picture O 0
resolved O 0
completely O 0
with O 0
cessation O 0
of O 0
the O 0
combined O 0
therapy O 0
. O 0

Baseline O 0
left O 0
ventricular O 0
function O 0
, O 0
assessed O 0
by O 0
cardiac O 0
catheterisation O 0
or O 0
nuclear O 0
angiography O 0
, O 0
was O 0
normal O 0
in O 0
two O 0
patients O 0
and O 0
only O 0
mildly O 0
reduced O 0
in O 0
the O 0
other O 0
. O 0

Simultaneously O 0
administration O 0
of O 0
beta B-Chemical 0
- I-Chemical 0
adrenergic I-Chemical 0
blocking I-Chemical 0
drugs I-Chemical 0
and O 0
verapamil B-Chemical 0
may O 0
result O 0
in O 0
profound O 0
adverse O 0
interactions O 0
and O 0
should O 0
only O 0
be O 0
administered O 0
with O 0
great O 0
caution O 0
. O 0

Comparison O 0
of O 0
the O 0
effectiveness O 0
of O 0
ranitidine B-Chemical 0
and O 0
cimetidine B-Chemical 0
in O 0
inhibiting O 0
acid O 0
secretion O 0
in O 0
patients O 0
with O 0
gastric O 0
hypersecretory O 0
states O 0
. O 0

The O 0
H2 O 0
- O 0
histamine B-Chemical 0
receptor O 0
antagonists O 0
ranitidine B-Chemical 0
and O 0
cimetidine B-Chemical 0
were O 0
compared O 0
for O 0
their O 0
abilities O 0
to O 0
control O 0
gastric O 0
acid O 0
hypersecretion O 0
on O 0
a O 0
short O 0
- O 0
and O 0
long O 0
- O 0
term O 0
basis O 0
in O 0
22 O 0
patients O 0
with O 0
gastric O 0
acid O 0
hypersecretory O 0
states O 0
. O 0

Nineteen O 0
patients O 0
had O 0
Zollinger B-Disease 0
- I-Disease 0
Ellison I-Disease 0
syndrome I-Disease 0
, O 0
one O 0
patient O 0
had O 0
systemic B-Disease 0
mastocytosis I-Disease 0
, O 0
and O 0
two O 0
patients O 0
had O 0
idiopathic O 0
hypersecretion O 0
. O 0

The O 0
rates O 0
of O 0
onset O 0
of O 0
the O 0
action O 0
of O 0
cimetidine B-Chemical 0
and O 0
ranitidine B-Chemical 0
were O 0
the O 0
same O 0
. O 0

The O 0
actions O 0
of O 0
both O 0
drugs O 0
were O 0
increased O 0
by O 0
anticholinergic O 0
agents O 0
, O 0
and O 0
there O 0
was O 0
a O 0
close O 0
correlation O 0
between O 0
the O 0
daily O 0
maintenance O 0
dose O 0
of O 0
each O 0
drug O 0
needed O 0
to O 0
control O 0
acid O 0
secretion O 0
. O 0

However O 0
, O 0
ranitidine B-Chemical 0
was O 0
threefold O 0
more O 0
potent O 0
than O 0
cimetidine B-Chemical 0
both O 0
in O 0
acute O 0
inhibition O 0
studies O 0
and O 0
in O 0
the O 0
median O 0
maintenance O 0
dose O 0
needed O 0
( O 0
1 O 0
. O 0
2 O 0
g O 0
per O 0
day O 0
for O 0
ranitidine B-Chemical 0
and O 0
3 O 0
. O 0
6 O 0
g O 0
per O 0
day O 0
for O 0
cimetidine B-Chemical 0
) O 0
. O 0

Sixty O 0
percent O 0
of O 0
the O 0
males O 0
developed O 0
breast O 0
changes O 0
or O 0
impotence B-Disease 0
while O 0
taking O 0
cimetidine B-Chemical 0
and O 0
in O 0
all O 0
cases O 0
these O 0
changes O 0
disappeared O 0
when O 0
cimetidine B-Chemical 0
was O 0
replaced O 0
by O 0
ranitidine B-Chemical 0
. O 0

Treatment O 0
with O 0
high O 0
doses O 0
of O 0
cimetidine B-Chemical 0
( O 0
one O 0
to O 0
60 O 0
months O 0
; O 0
median O 0
, O 0
11 O 0
months O 0
) O 0
or O 0
ranitidine B-Chemical 0
( O 0
two O 0
to O 0
31 O 0
months O 0
; O 0
median O 0
, O 0
14 O 0
months O 0
) O 0
was O 0
not O 0
associated O 0
with O 0
hepatic B-Disease 0
or I-Disease 0
hematologic I-Disease 0
toxicity I-Disease 0
or O 0
alterations O 0
of O 0
serum O 0
gastrin O 0
concentrations O 0
, O 0
but O 0
ranitidine B-Chemical 0
therapy O 0
was O 0
associated O 0
with O 0
a O 0
significantly O 0
lower O 0
serum O 0
creatinine B-Chemical 0
level O 0
than O 0
seen O 0
with O 0
cimetidine B-Chemical 0
therapy O 0
. O 0

The O 0
results O 0
show O 0
that O 0
both O 0
drugs O 0
can O 0
adequately O 0
inhibit O 0
acid O 0
secretion O 0
in O 0
patients O 0
with O 0
gastric O 0
hypersecretory O 0
states O 0
. O 0

Both O 0
are O 0
safe O 0
at O 0
high O 0
doses O 0
, O 0
but O 0
ranitidine B-Chemical 0
is O 0
threefold O 0
more O 0
potent O 0
and O 0
does O 0
not O 0
cause O 0
the O 0
antiandrogen O 0
side O 0
effects O 0
frequently O 0
seen O 0
with O 0
high O 0
doses O 0
of O 0
cimetidine B-Chemical 0
. O 0

Epileptogenic O 0
properties O 0
of O 0
enflurane B-Chemical 0
and O 0
their O 0
clinical O 0
interpretation O 0
. O 0

Three O 0
cases O 0
of O 0
EEG O 0
changes O 0
induced O 0
by O 0
single O 0
exposure O 0
to O 0
enflurane B-Chemical 0
anesthesia O 0
are O 0
reported O 0
. O 0

In O 0
one O 0
patient O 0
, O 0
enflurane B-Chemical 0
administered O 0
during O 0
a O 0
donor O 0
nephrectomy O 0
resulted O 0
in O 0
unexpected O 0
partial O 0
motor O 0
seizures B-Disease 0
. O 0

Until O 0
the O 0
cause O 0
of O 0
the O 0
seizures B-Disease 0
was O 0
correctly O 0
identified O 0
, O 0
the O 0
patient O 0
was O 0
inappropriately O 0
treated O 0
with O 0
anticonvulsants O 0
. O 0

Two O 0
other O 0
patients O 0
suffered O 0
from O 0
partial O 0
, O 0
complex O 0
and O 0
generalized O 0
seizures B-Disease 0
uncontrolled O 0
by O 0
medication O 0
. O 0

Epileptic B-Disease 0
foci O 0
delineated O 0
and O 0
activated O 0
by O 0
enflurane B-Chemical 0
were O 0
surgically O 0
ablated O 0
and O 0
the O 0
patients O 0
are O 0
now O 0
seizure B-Disease 0
- O 0
free O 0
. O 0

Previous O 0
exposures O 0
to O 0
enflurane B-Chemical 0
have O 0
to O 0
be O 0
disclosed O 0
to O 0
avoid O 0
mistakes O 0
in O 0
clinical O 0
interpretation O 0
of O 0
the O 0
EEG O 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
enflurane B-Chemical 0
may O 0
prove O 0
to O 0
be O 0
a O 0
safe O 0
fast O 0
acting O 0
activator O 0
of O 0
epileptic B-Disease 0
foci O 0
during O 0
corticography O 0
or O 0
depth O 0
electrode O 0
intraoperative O 0
recordings O 0
. O 0

Development O 0
of O 0
isoproterenol B-Chemical 0
- O 0
induced O 0
cardiac B-Disease 0
hypertrophy I-Disease 0
. O 0

The O 0
development O 0
of O 0
cardiac B-Disease 0
hypertrophy I-Disease 0
was O 0
studied O 0
in O 0
adult O 0
female O 0
Wistar O 0
rats O 0
following O 0
daily O 0
subcutaneous O 0
injections O 0
of O 0
isoproterenol B-Chemical 0
( O 0
ISO B-Chemical 0
) O 0
( O 0
0 O 0
. O 0
3 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
) O 0
. O 0

A O 0
time O 0
course O 0
was O 0
established O 0
for O 0
the O 0
change O 0
in O 0
tissue O 0
mass O 0
, O 0
RNA O 0
and O 0
DNA O 0
content O 0
, O 0
as O 0
well O 0
as O 0
hydroxyproline B-Chemical 0
content O 0
. O 0

Heart O 0
weight O 0
increased O 0
44 O 0
% O 0
after O 0
8 O 0
days O 0
of O 0
treatment O 0
with O 0
a O 0
half O 0
time O 0
of O 0
3 O 0
. O 0
4 O 0
days O 0
. O 0

Ventricular O 0
RNA O 0
content O 0
was O 0
elevated O 0
26 O 0
% O 0
after O 0
24 O 0
h O 0
of O 0
a O 0
single O 0
injection O 0
and O 0
reached O 0
a O 0
maximal O 0
level O 0
following O 0
8 O 0
days O 0
of O 0
therapy O 0
. O 0

The O 0
half O 0
time O 0
for O 0
RNA O 0
accumulation O 0
was O 0
2 O 0
. O 0
0 O 0
days O 0
. O 0

The O 0
total O 0
content O 0
of O 0
hydroxyproline B-Chemical 0
remained O 0
stable O 0
during O 0
the O 0
first O 0
2 O 0
days O 0
of O 0
treatment O 0
but O 0
increased O 0
46 O 0
% O 0
after O 0
4 O 0
days O 0
of O 0
therapy O 0
. O 0

Ventricular O 0
DNA O 0
content O 0
was O 0
unchanged O 0
during O 0
the O 0
early O 0
stage O 0
( O 0
1 O 0
- O 0
4 O 0
days O 0
) O 0
of O 0
hypertrophic B-Disease 0
growth O 0
but O 0
increased O 0
to O 0
a O 0
new O 0
steady O 0
- O 0
state O 0
level O 0
19 O 0
% O 0
above O 0
the O 0
controls O 0
after O 0
8 O 0
days O 0
of O 0
treatment O 0
. O 0

Intraventricular O 0
pressures O 0
and O 0
coronary O 0
flow O 0
measures O 0
were O 0
similar O 0
for O 0
control O 0
and O 0
experimental O 0
animals O 0
following O 0
4 O 0
days O 0
of O 0
developed O 0
hypertrophy B-Disease 0
. O 0

However O 0
, O 0
dP O 0
/ O 0
dt O 0
in O 0
the O 0
ISO B-Chemical 0
- O 0
treated O 0
hearts O 0
was O 0
slightly O 0
but 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
elevated O 0
. O 0

These O 0
data O 0
indicate O 0
that O 0
the O 0
adaptive O 0
response O 0
to O 0
ISO B-Chemical 0
shows O 0
an O 0
early O 0
hypertrophic B-Disease 0
phase O 0
( O 0
1 O 0
- O 0
4 O 0
days O 0
) O 0
characterized O 0
by O 0
a O 0
substantial O 0
increase O 0
in O 0
RNA O 0
content O 0
and O 0
cardiac O 0
mass O 0
in O 0
the O 0
absence O 0
of O 0
changes O 0
in O 0
DNA O 0
. O 0

However O 0
, O 0
prolonged O 0
stimulation O 0
( O 0
8 O 0
- O 0
12 O 0
days O 0
) O 0
appears O 0
to O 0
represent O 0
a O 0
complex O 0
integration O 0
of O 0
both O 0
cellular O 0
hypertrophy B-Disease 0
and O 0
hyperplasia B-Disease 0
within O 0
the O 0
heart O 0
. O 0

Multiple O 0
side O 0
effects O 0
of O 0
penicillamine B-Chemical 0
therapy O 0
in O 0
one O 0
patient O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
. O 0

Skin B-Disease 0
rashes I-Disease 0
, O 0
proteinuria B-Disease 0
, O 0
systemic B-Disease 0
lupus I-Disease 0
erythematosus I-Disease 0
, O 0
polymyositis B-Disease 0
and O 0
myasthenia B-Disease 0
gravis I-Disease 0
have O 0
all O 0
been O 0
recorded O 0
as O 0
complications O 0
of O 0
penicillamine B-Chemical 0
therapy O 0
in O 0
patients O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
. O 0

A O 0
patient O 0
who O 0
had O 0
developed O 0
all O 0
5 O 0
is O 0
now O 0
described O 0
. O 0

The O 0
skin B-Disease 0
lesion I-Disease 0
resembled O 0
elastosis B-Disease 0
perforans I-Disease 0
serpiginosa I-Disease 0
, O 0
which O 0
has O 0
been O 0
reported O 0
as O 0
a O 0
rare O 0
side O 0
effect O 0
in O 0
patients O 0
with O 0
Wilson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
but O 0
not O 0
in O 0
patients O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
treated O 0
with O 0
penicillamine B-Chemical 0
. O 0

Obsolete O 0
but O 0
dangerous O 0
antacid O 0
preparations O 0
. O 0

One O 0
case O 0
of O 0
acute O 0
hypercalcaemia B-Disease 0
and O 0
two O 0
of O 0
recurrent O 0
nephrolithiasis B-Disease 0
are O 0
reported O 0
in O 0
patients O 0
who O 0
had O 0
regularly O 0
consumed O 0
large O 0
amounts O 0
of O 0
calcium B-Chemical 0
carbon I-Chemical 0
- I-Chemical 0
ate I-Chemical 0
- O 0
sodium B-Chemical 0
bicarbonate I-Chemical 0
powders O 0
for O 0
more O 0
than O 0
20 O 0
years O 0
. O 0

The O 0
powders O 0
had O 0
been O 0
obtained O 0
from O 0
pharmacists O 0
unknown O 0
to O 0
the O 0
patients O 0
' O 0
medical O 0
practitioners O 0
. O 0

It O 0
is O 0
suggested O 0
that O 0
these O 0
preparations O 0
were O 0
responsible O 0
for O 0
the O 0
patient O 0
' O 0
s O 0
problems O 0
, O 0
and O 0
that O 0
such O 0
powders O 0
should O 0
no O 0
longer O 0
be O 0
freely O 0
obtainable O 0
. O 0

Doxorubicin B-Chemical 0
cardiomyopathy B-Disease 0
in O 0
children O 0
with O 0
left O 0
- O 0
sided O 0
Wilms B-Disease 0
tumor I-Disease 0
. O 0

Two O 0
children O 0
with O 0
Wilms B-Disease 0
tumor I-Disease 0
of O 0
the O 0
left O 0
kidney O 0
experienced O 0
severe O 0
anthracycline B-Chemical 0
cardiomyopathy B-Disease 0
after O 0
irradiation O 0
to O 0
the O 0
tumor B-Disease 0
bed O 0
and O 0
conventional O 0
dosage O 0
of O 0
doxorubicin B-Chemical 0
. O 0

The O 0
cardiomyopathy B-Disease 0
is O 0
attributed O 0
1 O 0
) O 0
to O 0
the O 0
fact O 0
that O 0
radiation O 0
fields O 0
for O 0
left O 0
Wilms B-Disease 0
tumor I-Disease 0
include O 0
the O 0
lower O 0
portion O 0
of O 0
the O 0
heart O 0
and O 0
2 O 0
) O 0
to O 0
the O 0
interaction O 0
of O 0
doxorubicin B-Chemical 0
and O 0
irradiation O 0
on O 0
cardiac O 0
muscle O 0
. O 0

It O 0
is O 0
recommended O 0
that O 0
doxorubicin B-Chemical 0
dosage O 0
be O 0
sharply O 0
restricted O 0
in O 0
children O 0
with O 0
Wilms B-Disease 0
tumor I-Disease 0
of O 0
the O 0
left O 0
kidney O 0
who O 0
receive O 0
postoperative O 0
irradiation O 0
. O 0

Effects O 0
of O 0
calcitonin O 0
on O 0
rat O 0
extrapyramidal O 0
motor O 0
system O 0
: O 0
behavioral O 0
and O 0
biochemical O 0
data O 0
. O 0

The O 0
effects O 0
of O 0
i O 0
. O 0
v O 0
. O 0
c O 0
. O 0
injection O 0
of O 0
human O 0
and O 0
salmon O 0
calcitonin O 0
on O 0
biochemical O 0
and O 0
behavioral O 0
parameters O 0
related O 0
to O 0
the O 0
extrapyramidal O 0
motor O 0
system O 0
, O 0
were O 0
investigated O 0
in O 0
male O 0
rats O 0
. O 0

Calcitonin O 0
injection O 0
resulted O 0
in O 0
a O 0
potentiation O 0
of O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
and O 0
a O 0
partial O 0
prevention O 0
of O 0
apomorphine B-Chemical 0
- O 0
induced O 0
hyperactivity B-Disease 0
. O 0

Moreover O 0
calcitonin O 0
induced O 0
a O 0
significant O 0
decrease O 0
in O 0
nigral O 0
GAD O 0
activity O 0
but O 0
no O 0
change O 0
in O 0
striatal O 0
DA B-Chemical 0
and O 0
DOPAC B-Chemical 0
concentration O 0
or O 0
GAD O 0
activity O 0
. O 0

The O 0
results O 0
are O 0
discussed O 0
in O 0
view O 0
of O 0
a O 0
primary O 0
action O 0
of O 0
calcitonin O 0
on O 0
the O 0
striatonigral O 0
GABAergic O 0
pathway O 0
mediating O 0
the O 0
DA B-Chemical 0
- O 0
related O 0
behavioral O 0
messages O 0
of O 0
striatal O 0
origin O 0
. O 0

Naloxazone B-Chemical 0
pretreatment O 0
modifies O 0
cardiorespiratory O 0
, O 0
temperature O 0
, O 0
and O 0
behavioral O 0
effects O 0
of O 0
morphine B-Chemical 0
. O 0

Behavioral O 0
and O 0
cardiorespiratory O 0
responses O 0
to O 0
a O 0
lethal O 0
dose O 0
of O 0
morphine B-Chemical 0
were O 0
evaluated O 0
in O 0
rats O 0
pretreated O 0
with O 0
saline O 0
or O 0
naloxazone B-Chemical 0
, O 0
an O 0
antagonist O 0
of O 0
high O 0
- O 0
affinity O 0
mu O 0
1 O 0
opioid O 0
receptors O 0
. O 0

Pretreatment O 0
with O 0
naloxazone B-Chemical 0
significantly O 0
blocked O 0
morphine B-Chemical 0
analgesia B-Disease 0
, O 0
catalepsy B-Disease 0
and O 0
hypothermia B-Disease 0
at O 0
a O 0
dose O 0
which O 0
completely O 0
eliminated O 0
high O 0
- O 0
affinity O 0
binding O 0
in O 0
brain O 0
membranes O 0
. O 0

Moreover O 0
, O 0
naloxazone B-Chemical 0
significantly O 0
attenuated O 0
the O 0
morphine B-Chemical 0
- O 0
induced O 0
hypotension B-Disease 0
and O 0
respiratory B-Disease 0
depression I-Disease 0
, O 0
whereas O 0
morphine B-Chemical 0
- O 0
induced O 0
bradycardia B-Disease 0
was O 0
less O 0
affected O 0
. O 0

Results O 0
indicate O 0
that O 0
subpopulations O 0
of O 0
mu O 0
receptors O 0
may O 0
mediate O 0
selective O 0
behavioral O 0
and O 0
cardiorespiratory O 0
responses O 0
to O 0
morphine B-Chemical 0
. O 0

Modification O 0
of O 0
drug O 0
action O 0
by O 0
hyperammonemia B-Disease 0
. O 0

Pretreatment O 0
with O 0
ammonium B-Chemical 0
acetate I-Chemical 0
( O 0
NH4Ac B-Chemical 0
) O 0
( O 0
6 O 0
mmol O 0
/ O 0
kg O 0
s O 0
. O 0
c O 0
. O 0
) O 0
approximately O 0
doubled O 0
the O 0
time O 0
morphine B-Chemical 0
- O 0
treated O 0
mice O 0
remained O 0
on O 0
a O 0
hot O 0
surface O 0
and O 0
similarly O 0
increased O 0
muscular O 0
incoordination B-Disease 0
by O 0
diazepam B-Chemical 0
, O 0
but O 0
NH4Ac B-Chemical 0
treatment O 0
alone O 0
had O 0
no O 0
effect O 0
. O 0

Thus O 0
, O 0
hyperammonemia B-Disease 0
is O 0
capable O 0
of O 0
altering O 0
drug O 0
action O 0
and O 0
must O 0
be O 0
considered O 0
along O 0
with O 0
impaired O 0
drug O 0
metabolism O 0
in O 0
enhanced O 0
drug O 0
responses O 0
associated O 0
with O 0
liver B-Disease 0
disease I-Disease 0
. O 0

Experiments O 0
in O 0
vitro O 0
showed O 0
that O 0
acetylcholine B-Chemical 0
- O 0
induced O 0
catecholamine B-Chemical 0
release O 0
from O 0
bovine O 0
adrenal O 0
medulla O 0
is O 0
depressed O 0
as O 0
much O 0
as O 0
50 O 0
% O 0
by O 0
0 O 0
. O 0
3 O 0
mM O 0
NH4Ac B-Chemical 0
and O 0
KCl B-Chemical 0
- O 0
induced O 0
contractions O 0
of O 0
guinea O 0
- O 0
pig O 0
ileum O 0
were O 0
inhibited O 0
20 O 0
% O 0
by O 0
5 O 0
mM O 0
NH4Ac B-Chemical 0
. O 0

Addition O 0
of O 0
excess O 0
calcium B-Chemical 0
reversed O 0
the O 0
depression B-Disease 0
in O 0
both O 0
tissues O 0
, O 0
but O 0
calcium B-Chemical 0
- O 0
independent O 0
catecholamine B-Chemical 0
release O 0
by O 0
acetaldehyde B-Chemical 0
was O 0
not O 0
blocked O 0
by O 0
NH4Ac B-Chemical 0
. O 0

These O 0
results O 0
suggested O 0
that O 0
ammonia B-Chemical 0
blocks O 0
calcium B-Chemical 0
channels O 0
. O 0

Parallels O 0
in O 0
the O 0
actions O 0
of O 0
NH4Ac B-Chemical 0
and O 0
the O 0
calcium B-Chemical 0
channel O 0
blocker O 0
verapamil B-Chemical 0
support O 0
this O 0
concept O 0
. O 0

Both O 0
verapamil B-Chemical 0
( O 0
10 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
and O 0
NH4Ac B-Chemical 0
pretreatment O 0
enhanced O 0
morphine B-Chemical 0
analgesia B-Disease 0
- O 0
and O 0
diazepam B-Chemical 0
- O 0
induced O 0
muscular O 0
incoordination B-Disease 0
and O 0
antagonized O 0
amphetamine B-Chemical 0
- O 0
induced O 0
motor O 0
activity O 0
, O 0
and O 0
neither O 0
verapamil B-Chemical 0
nor O 0
NH4Ac B-Chemical 0
affected O 0
the O 0
convulsant O 0
action O 0
of O 0
metrazol B-Chemical 0
. O 0

The O 0
data O 0
suggest O 0
that O 0
hyperammonemia B-Disease 0
exerts O 0
a O 0
calcium B-Chemical 0
channel O 0
blocking O 0
action O 0
which O 0
enhances O 0
the O 0
effects O 0
of O 0
central O 0
nervous O 0
system O 0
depressants O 0
and O 0
certain O 0
opioid O 0
analgesics O 0
. O 0

Levodopa B-Chemical 0
- O 0
induced O 0
dyskinesia B-Disease 0
and O 0
thalamotomy O 0
. O 0

Levodopa B-Chemical 0
- O 0
induced O 0
dyskinesia B-Disease 0
of O 0
the O 0
limbs O 0
in O 0
thirteen O 0
cases O 0
of O 0
Parkinsonism B-Disease 0
, O 0
which O 0
was O 0
choreic O 0
, O 0
ballistic O 0
or O 0
dystonic B-Disease 0
in O 0
type O 0
, O 0
was O 0
alleviated O 0
almost O 0
completely O 0
by O 0
stereotaxic O 0
surgery O 0
using O 0
a O 0
microelectrode O 0
technique O 0
for O 0
the O 0
ventralis O 0
oralis O 0
anterior O 0
and O 0
posterior O 0
nuclei O 0
of O 0
the O 0
thalamus O 0
, O 0
but O 0
much O 0
less O 0
by O 0
the O 0
ventralis O 0
intermedius O 0
nucleus O 0
. O 0

Control O 0
of O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
by O 0
thalamic B-Disease 0
lesions I-Disease 0
in O 0
the O 0
course O 0
of O 0
routine O 0
treatment O 0
of O 0
Parkinsonism B-Disease 0
is O 0
discussed O 0
. O 0

Treatment O 0
of O 0
ifosfamide B-Chemical 0
- O 0
induced O 0
urothelial B-Disease 0
toxicity I-Disease 0
by O 0
oral O 0
administration O 0
of O 0
sodium B-Chemical 0
2 I-Chemical 0
- I-Chemical 0
mercaptoethane I-Chemical 0
sulphonate I-Chemical 0
( O 0
MESNA B-Chemical 0
) O 0
to O 0
patients O 0
with O 0
inoperable O 0
lung B-Disease 0
cancer I-Disease 0
. O 0

The O 0
protective O 0
effect O 0
of O 0
oral O 0
administration O 0
of O 0
the O 0
thiol B-Chemical 0
compound O 0
sodium B-Chemical 0
2 I-Chemical 0
- I-Chemical 0
mercaptoethane I-Chemical 0
sulphonate I-Chemical 0
( O 0
MESNA B-Chemical 0
) O 0
against O 0
urothelial B-Disease 0
toxicity I-Disease 0
induced O 0
by O 0
ifosfamide B-Chemical 0
( O 0
IF B-Chemical 0
) O 0
was O 0
tested O 0
in O 0
a O 0
group O 0
of O 0
45 O 0
patients O 0
with O 0
inoperable O 0
lung B-Disease 0
cancer I-Disease 0
under O 0
treatment O 0
with O 0
IF B-Chemical 0
( O 0
2250 O 0
mg O 0
/ O 0
m2 O 0
on O 0
days O 0
2 O 0
- O 0
5 O 0
) O 0
as O 0
part O 0
of O 0
a O 0
polychemotherapy O 0
regimen O 0
repeated O 0
in O 0
a O 0
4 O 0
- O 0
week O 0
cycle O 0
. O 0

MESNA B-Chemical 0
was O 0
given O 0
orally O 0
on O 0
the O 0
days O 0
of O 0
treatment O 0
with O 0
IF B-Chemical 0
in O 0
3 O 0
doses O 0
of O 0
840 O 0
mg O 0
/ O 0
m2 O 0
, O 0
each O 0
administered O 0
at O 0
0 O 0
hr O 0
( O 0
= O 0
injection O 0
of O 0
IF B-Chemical 0
) O 0
, O 0
4 O 0
hr O 0
and O 0
8 O 0
hr O 0
p O 0
. O 0
i O 0
. O 0

Out O 0
of O 0
a O 0
total O 0
of O 0
88 O 0
courses O 0
of O 0
this O 0
treatment O 0
we O 0
observed O 0
10 O 0
episodes O 0
of O 0
asymptomatic O 0
microscopic O 0
haematuria B-Disease 0
and O 0
no O 0
episodes O 0
of O 0
gross O 0
haematuria B-Disease 0
. O 0

In O 0
this O 0
group O 0
of O 0
45 O 0
patients O 0
under O 0
protection O 0
with O 0
MESNA B-Chemical 0
there O 0
were O 0
5 O 0
complete O 0
remissions O 0
and O 0
9 O 0
partial O 0
remissions O 0
( O 0
total O 0
31 O 0
% O 0
) O 0
. O 0

A O 0
further O 0
group O 0
of O 0
25 O 0
patients O 0
under O 0
polychemotherapy O 0
with O 0
IF B-Chemical 0
were O 0
treated O 0
by O 0
conventional O 0
prophylactic O 0
measures O 0
( O 0
raised O 0
fluid O 0
intake O 0
and O 0
forced O 0
diuresis O 0
) O 0
. O 0

In O 0
this O 0
group O 0
there O 0
were O 0
1 O 0
complete O 0
and O 0
5 O 0
partial O 0
remissions O 0
( O 0
total O 0
24 O 0
% O 0
) O 0
, O 0
but O 0
nearly O 0
all O 0
patients O 0
developed O 0
either O 0
gross O 0
haematuria B-Disease 0
and O 0
/ O 0
or O 0
symptoms O 0
of O 0
bladder B-Disease 0
irritation I-Disease 0
( O 0
cystitis B-Disease 0
and O 0
pollakisuria B-Disease 0
) O 0
. O 0

There O 0
were O 0
no O 0
appreciable O 0
differences O 0
between O 0
the O 0
MESNA B-Chemical 0
series O 0
and O 0
the O 0
conventional O 0
prophylaxis O 0
series O 0
with O 0
respect O 0
to O 0
either O 0
haematological O 0
or O 0
systemic O 0
toxicity B-Disease 0
of O 0
the O 0
cytostatic O 0
treatment O 0
. O 0

Our O 0
results O 0
support O 0
the O 0
view O 0
that O 0
MESNA B-Chemical 0
, O 0
given O 0
orally O 0
in O 0
conjunction O 0
with O 0
combined O 0
cytostatic O 0
regimens O 0
which O 0
include O 0
IF B-Chemical 0
, O 0
simplifies O 0
the O 0
treatment O 0
and O 0
provides O 0
optimum O 0
protection O 0
for O 0
the O 0
urinary O 0
epithelium O 0
. O 0

Protection O 0
with O 0
oral O 0
MESNA B-Chemical 0
is O 0
particularly O 0
suitable O 0
for O 0
outpatients O 0
. O 0

Myoclonic B-Disease 0
, I-Disease 0
atonic I-Disease 0
, I-Disease 0
and I-Disease 0
absence I-Disease 0
seizures I-Disease 0
following O 0
institution O 0
of O 0
carbamazepine B-Chemical 0
therapy O 0
in O 0
children O 0
. O 0

Five O 0
children O 0
, O 0
aged O 0
3 O 0
to O 0
11 O 0
years O 0
, O 0
treated O 0
with O 0
carbamazepine B-Chemical 0
for O 0
epilepsy B-Disease 0
, O 0
had O 0
an O 0
acute O 0
aberrant O 0
reaction O 0
characterized O 0
by O 0
the O 0
onset O 0
of O 0
myoclonic B-Disease 0
, I-Disease 0
atypical I-Disease 0
absence I-Disease 0
and I-Disease 0
/ I-Disease 0
or I-Disease 0
atonic I-Disease 0
( I-Disease 0
minor I-Disease 0
motor I-Disease 0
) I-Disease 0
seizures I-Disease 0
within O 0
a O 0
few O 0
days O 0
. O 0

When O 0
the O 0
carbamazepine B-Chemical 0
was O 0
discontinued O 0
, O 0
two O 0
of O 0
the O 0
children O 0
returned O 0
to O 0
their O 0
former O 0
state O 0
very O 0
quickly O 0
, O 0
two O 0
had O 0
the O 0
minor O 0
motor O 0
seizures B-Disease 0
resolve O 0
in O 0
3 O 0
and O 0
6 O 0
months O 0
, O 0
and O 0
one O 0
had O 0
the O 0
seizures B-Disease 0
persist O 0
. O 0

The O 0
child O 0
in O 0
whom O 0
the O 0
seizures B-Disease 0
persisted O 0
was O 0
later O 0
found O 0
to O 0
have O 0
ceroid B-Disease 0
lipofuscinosis I-Disease 0
. O 0

The O 0
other O 0
children O 0
are O 0
doing O 0
well O 0
on O 0
other O 0
anticonvulsants O 0
. O 0

Effect O 0
of O 0
prostaglandin B-Chemical 0
synthetase O 0
inhibitors O 0
on O 0
experimentally O 0
induced O 0
convulsions B-Disease 0
in O 0
rats O 0
. O 0

To O 0
investigate O 0
the O 0
relationship O 0
of O 0
prostaglandins B-Chemical 0
( O 0
PGs B-Chemical 0
) O 0
to O 0
seizure B-Disease 0
induction O 0
, O 0
the O 0
effects O 0
of O 0
six O 0
PG O 0
synthetase O 0
inhibitors O 0
on O 0
convulsions B-Disease 0
induced O 0
by O 0
flurothyl B-Chemical 0
, O 0
picrotoxin B-Chemical 0
, O 0
pentetrazol B-Chemical 0
( O 0
PTZ B-Chemical 0
) O 0
, O 0
electroshock O 0
or O 0
bicuculline B-Chemical 0
were O 0
evaluated O 0
. O 0

Ibuprofen B-Chemical 0
, O 0
sulindac B-Chemical 0
, O 0
mefenamic B-Chemical 0
acid I-Chemical 0
, O 0
and O 0
low O 0
dose O 0
meclofenamic B-Chemical 0
acid I-Chemical 0
increased O 0
the O 0
latency O 0
- O 0
to O 0
- O 0
onset O 0
in O 0
the O 0
flurothyl B-Chemical 0
and O 0
/ O 0
or O 0
PTZ B-Chemical 0
models O 0
; O 0
the O 0
electroshock O 0
, O 0
picrotoxin B-Chemical 0
and O 0
bicuculline B-Chemical 0
models 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
pretreatment O 0
agents O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
PGs B-Chemical 0
are O 0
involved O 0
in O 0
the O 0
mechanism O 0
( O 0
s O 0
) O 0
underlying O 0
fluorthyl B-Chemical 0
- O 0
and O 0
PTZ B-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
, O 0
but O 0
not O 0
picrotoxin B-Chemical 0
- O 0
, O 0
electroshock O 0
- O 0
, O 0
or O 0
bicuculline B-Chemical 0
- O 0
induced O 0
convulsions B-Disease 0
. O 0

Acute O 0
changes O 0
of O 0
blood O 0
ammonia B-Chemical 0
may O 0
predict O 0
short O 0
- O 0
term O 0
adverse O 0
effects O 0
of O 0
valproic B-Chemical 0
acid I-Chemical 0
. O 0

Valproic B-Chemical 0
acid I-Chemical 0
( O 0
VPA B-Chemical 0
) O 0
was O 0
given O 0
to O 0
24 O 0
epileptic B-Disease 0
patients O 0
who O 0
were O 0
already O 0
being O 0
treated O 0
with O 0
other O 0
antiepileptic O 0
drugs O 0
. O 0

A O 0
standardized O 0
loading O 0
dose O 0
of O 0
VPA B-Chemical 0
was O 0
administered O 0
, O 0
and O 0
venous O 0
blood O 0
was O 0
sampled O 0
at O 0
0 O 0
, O 0
1 O 0
, O 0
2 O 0
, O 0
3 O 0
, O 0
and O 0
4 O 0
hours O 0
. O 0

Ammonia B-Chemical 0
( O 0
NH3 B-Chemical 0
) O 0
was O 0
higher O 0
in O 0
patients O 0
who O 0
, O 0
during O 0
continuous O 0
therapy O 0
, O 0
complained O 0
of O 0
drowsiness B-Disease 0
( O 0
7 O 0
patients O 0
) O 0
than O 0
in O 0
those O 0
who O 0
were O 0
symptom O 0
- O 0
free O 0
( O 0
17 O 0
patients O 0
) O 0
, O 0
although O 0
VPA B-Chemical 0
plasma O 0
levels O 0
were O 0
similar O 0
in O 0
both O 0
groups O 0
. O 0

By O 0
measuring O 0
VPA B-Chemical 0
- O 0
induced O 0
changes O 0
of O 0
blood O 0
NH3 B-Chemical 0
content O 0
, O 0
it O 0
may O 0
be O 0
possible O 0
to O 0
identify O 0
patients O 0
at O 0
higher O 0
risk O 0
of O 0
obtundation O 0
when O 0
VPA B-Chemical 0
is O 0
given O 0
chronically O 0
. O 0

Effect O 0
of O 0
captopril B-Chemical 0
on O 0
pre O 0
- O 0
existing O 0
and O 0
aminonucleoside B-Chemical 0
- O 0
induced O 0
proteinuria B-Disease 0
in O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
. O 0

Proteinuria B-Disease 0
is O 0
a O 0
side O 0
effect O 0
of O 0
captopril B-Chemical 0
treatment O 0
in O 0
hypertensive B-Disease 0
patients O 0
. O 0

The O 0
possibility O 0
of O 0
reproducing O 0
the O 0
same O 0
renal B-Disease 0
abnormality I-Disease 0
with O 0
captopril B-Chemical 0
was O 0
examined O 0
in O 0
SHR O 0
. O 0

Oral O 0
administration O 0
of O 0
captopril B-Chemical 0
at O 0
100 O 0
mg O 0
/ O 0
kg O 0
for O 0
14 O 0
days O 0
failed O 0
to O 0
aggravate O 0
proteinuria B-Disease 0
pre O 0
- O 0
existing O 0
in O 0
SHR O 0
. O 0

Also O 0
, O 0
captopril B-Chemical 0
treatment O 0
failed O 0
to O 0
potentiate O 0
or O 0
facilitate O 0
development O 0
of O 0
massive O 0
proteinuria B-Disease 0
invoked O 0
by O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
in O 0
SHR O 0
. O 0

Captopril B-Chemical 0
had O 0
little O 0
or O 0
no O 0
demonstrable O 0
effects O 0
on O 0
serum O 0
electrolyte O 0
concentrations O 0
, O 0
excretion O 0
of O 0
urine O 0
, O 0
sodium B-Chemical 0
and O 0
potassium B-Chemical 0
, O 0
endogenous O 0
creatinine B-Chemical 0
clearance O 0
, O 0
body O 0
weight O 0
, O 0
and O 0
food O 0
and O 0
water O 0
consumption O 0
. O 0

However O 0
, O 0
ketone B-Chemical 0
bodies O 0
were O 0
consistently O 0
present O 0
in O 0
urine O 0
and O 0
several O 0
lethalities O 0
occurred O 0
during O 0
multiple O 0
dosing O 0
of O 0
captopril B-Chemical 0
in O 0
SHR O 0
. O 0

Complete O 0
heart B-Disease 0
block I-Disease 0
following O 0
a O 0
single O 0
dose O 0
of O 0
trazodone B-Chemical 0
. O 0

Forty O 0
minutes O 0
after O 0
receiving O 0
a O 0
single O 0
starting O 0
dose O 0
of O 0
trazodone B-Chemical 0
, O 0
a O 0
patient O 0
developed O 0
complete O 0
heart B-Disease 0
block I-Disease 0
. O 0

The O 0
case O 0
illustrates O 0
that O 0
, O 0
despite O 0
the O 0
results O 0
of O 0
earlier O 0
studies O 0
, O 0
trazodone B-Chemical 0
' O 0
s O 0
effect O 0
on O 0
cardiac O 0
conduction O 0
may O 0
be O 0
severe O 0
in O 0
individuals O 0
at O 0
risk O 0
for O 0
conduction O 0
delay O 0
. O 0

Phenobarbital B-Chemical 0
- O 0
induced O 0
dyskinesia B-Disease 0
in O 0
a O 0
neurologically B-Disease 0
- I-Disease 0
impaired I-Disease 0
child O 0
. O 0

A O 0
2 O 0
- O 0
year O 0
- O 0
old O 0
child O 0
with O 0
known O 0
neurologic B-Disease 0
impairment I-Disease 0
developed O 0
a O 0
dyskinesia B-Disease 0
soon O 0
after O 0
starting O 0
phenobarbital B-Chemical 0
therapy O 0
for O 0
seizures B-Disease 0
. O 0

Known O 0
causes O 0
of O 0
movement B-Disease 0
disorders I-Disease 0
were O 0
eliminated O 0
after O 0
evaluation O 0
. O 0

On O 0
repeat O 0
challenge O 0
with O 0
phenobarbital B-Chemical 0
, O 0
the O 0
dyskinesia B-Disease 0
recurred O 0
. O 0

Phenobarbital B-Chemical 0
should O 0
be O 0
added O 0
to O 0
the O 0
list O 0
of O 0
anticonvulsant O 0
drugs O 0
that O 0
can O 0
cause O 0
movement B-Disease 0
disorders I-Disease 0
. O 0

Effects O 0
of O 0
amine B-Chemical 0
pretreatment O 0
on O 0
ketamine B-Chemical 0
catatonia B-Disease 0
in O 0
pinealectomized O 0
or O 0
hypophysectomized O 0
animals O 0
. O 0

The O 0
present O 0
studies O 0
were O 0
designed O 0
to O 0
clarify O 0
the O 0
role O 0
of O 0
catecholamines B-Chemical 0
and O 0
pineal O 0
idolamines O 0
on O 0
ketamine B-Chemical 0
- O 0
induced O 0
catatonia B-Disease 0
in O 0
the O 0
intact O 0
, O 0
pinealectomized O 0
or O 0
hypophysectomized O 0
chick O 0
and O 0
rat O 0
. O 0

In O 0
the O 0
pinealectomized O 0
chick O 0
, O 0
pretreatment O 0
with O 0
dopamine B-Chemical 0
increased O 0
the O 0
duration O 0
of O 0
catatonia B-Disease 0
( O 0
DOC O 0
) O 0
after O 0
ketamine B-Chemical 0
, O 0
but O 0
pretreatment O 0
with O 0
norepinephrine B-Chemical 0
did O 0
not O 0
. O 0

The O 0
pineal O 0
indolamines O 0
exhibited O 0
mixed O 0
actions O 0
. O 0

Serotonin B-Chemical 0
and O 0
N B-Chemical 0
- I-Chemical 0
acetyl I-Chemical 0
serotonin I-Chemical 0
which O 0
augmented O 0
ketamine B-Chemical 0
DOC O 0
, O 0
did O 0
not O 0
do O 0
so O 0
in O 0
the O 0
absence O 0
of O 0
the O 0
pineal O 0
gland O 0
, O 0
whereas O 0
melatonin B-Chemical 0
potentiated O 0
the O 0
ketamine B-Chemical 0
DOC O 0
in O 0
both O 0
the O 0
intact O 0
and O 0
pinealectomized O 0
chick O 0
. O 0

Ketamine B-Chemical 0
was O 0
more O 0
potent O 0
in O 0
the O 0
hypophysectomized O 0
chick O 0
and O 0
the O 0
circadian O 0
rhythm O 0
noted O 0
in O 0
the O 0
intact O 0
chick O 0
was O 0
absent O 0
; O 0
furthermore O 0
, O 0
melatonin B-Chemical 0
did O 0
not O 0
augment O 0
the O 0
ketamine B-Chemical 0
DOC O 0
whereas O 0
dopamine B-Chemical 0
continued O 0
to O 0
do O 0
so O 0
. O 0

This O 0
study O 0
did O 0
not O 0
demonstrate O 0
a O 0
species O 0
difference O 0
regarding O 0
the O 0
role O 0
of O 0
the O 0
amines B-Chemical 0
on O 0
the O 0
pineal O 0
in O 0
spite O 0
of O 0
the O 0
immature O 0
blood O 0
- O 0
brain O 0
barrier O 0
in O 0
the O 0
young O 0
chick O 0
and O 0
the O 0
intact O 0
barrier O 0
in O 0
the O 0
rat O 0
. O 0

In O 0
addition O 0
, O 0
these O 0
data O 0
indicate O 0
a O 0
direct O 0
role O 0
of O 0
the O 0
pituitary O 0
in O 0
the O 0
augmentation O 0
of O 0
ketamine B-Chemical 0
DOC O 0
induced O 0
by O 0
melatonin B-Chemical 0
. O 0

Furthermore O 0
, O 0
dopamine B-Chemical 0
appeared O 0
to O 0
act O 0
on O 0
systems O 0
more O 0
closely O 0
involved O 0
with O 0
the O 0
induction O 0
of O 0
ketamine B-Chemical 0
catatonia B-Disease 0
rather O 0
than O 0
directly O 0
on O 0
the O 0
pituitary O 0
. O 0

Heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
, O 0
thrombosis B-Disease 0
, O 0
and O 0
hemorrhage B-Disease 0
. O 0

Sixty O 0
- O 0
two O 0
patients O 0
with O 0
a O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombocytopenia B-Disease 0
are O 0
reported O 0
. O 0

Clinical O 0
manifestations O 0
of O 0
this O 0
disorder O 0
include O 0
hemorrhage B-Disease 0
or O 0
, O 0
more O 0
frequently O 0
, O 0
thromboembolic B-Disease 0
events O 0
in O 0
patients O 0
receiving O 0
heparin B-Chemical 0
. O 0

Laboratory O 0
testing O 0
has O 0
revealed O 0
a B-Disease 0
falling I-Disease 0
platelet I-Disease 0
count I-Disease 0
, O 0
increased O 0
resistance O 0
to O 0
heparin B-Chemical 0
, O 0
and O 0
aggregation O 0
of O 0
platelets O 0
by O 0
the O 0
patient O 0
' O 0
s O 0
plasma O 0
when O 0
heparin B-Chemical 0
is O 0
added O 0
. O 0

Immunologic O 0
testing O 0
has O 0
demonstrated O 0
the O 0
presence O 0
of O 0
a O 0
heparin B-Chemical 0
- O 0
dependent O 0
platelet O 0
membrane O 0
antibody O 0
. O 0

The O 0
20 O 0
deaths O 0
, O 0
52 O 0
hemorrhagic B-Disease 0
and I-Disease 0
thromboembolic I-Disease 0
complications I-Disease 0
, O 0
and O 0
21 O 0
surgical O 0
procedures O 0
to O 0
manage O 0
the O 0
complications O 0
confirm O 0
the O 0
seriousness O 0
of O 0
the O 0
disorder O 0
. O 0

Specific O 0
risk O 0
factors O 0
have O 0
not O 0
been O 0
identified O 0
; O 0
therefore O 0
, O 0
all O 0
patients O 0
receiving O 0
heparin B-Chemical 0
should O 0
be O 0
monitored O 0
. O 0

If O 0
the O 0
platelet O 0
count O 0
falls O 0
to O 0
less O 0
than O 0
100 O 0
, O 0
000 O 0
/ O 0
mm3 O 0
, O 0
while O 0
the O 0
patient O 0
is O 0
receiving O 0
heparin B-Chemical 0
, O 0
platelet B-Disease 0
aggregation I-Disease 0
testing O 0
, O 0
using O 0
the O 0
patient O 0
' O 0
s O 0
plasma O 0
, O 0
is O 0
indicated O 0
. O 0

Management O 0
consists O 0
of O 0
cessation O 0
of O 0
heparin B-Chemical 0
, O 0
platelet O 0
anti O 0
- O 0
aggregating O 0
agents O 0
, O 0
and O 0
alternate O 0
forms O 0
of O 0
anticoagulation O 0
when O 0
indicated O 0
. O 0

Ventricular B-Disease 0
fibrillation I-Disease 0
from O 0
diatrizoate B-Chemical 0
with O 0
and O 0
without O 0
chelating O 0
agents O 0
. O 0

The O 0
toxicity B-Disease 0
of O 0
Renografin B-Chemical 0
76 I-Chemical 0
% I-Chemical 0
was O 0
compared O 0
with O 0
that O 0
of O 0
Hypaque B-Chemical 0
76 I-Chemical 0
% I-Chemical 0
by O 0
selective O 0
injection O 0
of O 0
each O 0
into O 0
the O 0
right O 0
coronary O 0
artery O 0
of O 0
dogs O 0
. O 0

Renografin B-Chemical 0
contains O 0
the O 0
chelating O 0
agents O 0
sodium B-Chemical 0
citrate I-Chemical 0
and O 0
disodium B-Chemical 0
edetate I-Chemical 0
, O 0
while O 0
Hypaque B-Chemical 0
contains O 0
calcium B-Chemical 0
disodium I-Chemical 0
edetate I-Chemical 0
and O 0
no O 0
sodium B-Chemical 0
citrate I-Chemical 0
. O 0

Ventricular B-Disease 0
fibrillation I-Disease 0
occurred O 0
significantly O 0
more O 0
often O 0
with O 0
Renografin B-Chemical 0
, O 0
suggesting O 0
that O 0
chelating O 0
agents O 0
contribute O 0
to O 0
toxicity B-Disease 0
in O 0
coronary O 0
angiography O 0
. O 0

Long O 0
- O 0
term O 0
efficacy O 0
and O 0
toxicity B-Disease 0
of O 0
high O 0
- O 0
dose O 0
amiodarone B-Chemical 0
therapy O 0
for O 0
ventricular B-Disease 0
tachycardia I-Disease 0
or O 0
ventricular B-Disease 0
fibrillation I-Disease 0
. O 0

Amiodarone B-Chemical 0
was O 0
administered O 0
to O 0
154 O 0
patients O 0
who O 0
had O 0
sustained O 0
, O 0
symptomatic O 0
ventricular B-Disease 0
tachycardia I-Disease 0
( O 0
VT B-Disease 0
) O 0
( O 0
n O 0
= O 0
118 O 0
) O 0
or O 0
a O 0
cardiac B-Disease 0
arrest I-Disease 0
( O 0
n O 0
= O 0
36 O 0
) O 0
and O 0
who O 0
were O 0
refractory O 0
to O 0
conventional O 0
antiarrhythmic O 0
drugs O 0
. O 0

The O 0
loading O 0
dose O 0
was O 0
800 O 0
mg O 0
/ O 0
day O 0
for O 0
6 O 0
weeks O 0
and O 0
the O 0
maintenance O 0
dose O 0
was O 0
600 O 0
mg O 0
/ O 0
day O 0
. O 0

Sixty O 0
- O 0
nine O 0
percent O 0
of O 0
patients O 0
continued O 0
treatment O 0
with O 0
amiodarone B-Chemical 0
and O 0
had O 0
no O 0
recurrence O 0
of O 0
symptomatic O 0
VT B-Disease 0
or O 0
ventricular B-Disease 0
fibrillation I-Disease 0
( O 0
VF B-Disease 0
) O 0
over O 0
a O 0
follow O 0
- O 0
up O 0
of O 0
6 O 0
to O 0
52 O 0
months O 0
( O 0
mean O 0
+ O 0
/ O 0
- O 0
standard O 0
deviation O 0
14 O 0
. O 0
2 O 0
+ O 0
/ O 0
- O 0
8 O 0
. O 0
2 O 0
) O 0
. O 0

Six O 0
percent O 0
of O 0
the O 0
patients O 0
had O 0
a O 0
nonfatal O 0
recurrence O 0
of O 0
VT B-Disease 0
and O 0
were O 0
successfully O 0
managed O 0
by O 0
continuing O 0
amiodarone B-Chemical 0
at O 0
a O 0
higher O 0
dose O 0
or O 0
by O 0
the O 0
addition O 0
of O 0
a O 0
conventional O 0
antiarrhythmic O 0
drug O 0
. O 0

One O 0
or O 0
more O 0
adverse O 0
drug O 0
reactions O 0
occurred O 0
in O 0
51 O 0
% O 0
of O 0
patients O 0
. O 0

Adverse O 0
effects O 0
forced O 0
a O 0
reduction O 0
in O 0
the O 0
dose O 0
of O 0
amiodarone B-Chemical 0
in O 0
41 O 0
% O 0
and O 0
discontinuation O 0
of O 0
amiodarone B-Chemical 0
in O 0
10 O 0
% O 0
of O 0
patients O 0
. O 0

The O 0
most O 0
common O 0
symptomatic O 0
adverse O 0
reactions O 0
were O 0
tremor B-Disease 0
or O 0
ataxia B-Disease 0
( O 0
35 O 0
% O 0
) O 0
, O 0
nausea B-Disease 0
and O 0
anorexia B-Disease 0
( O 0
8 O 0
% O 0
) O 0
, O 0
visual B-Disease 0
halos I-Disease 0
or I-Disease 0
blurring I-Disease 0
( O 0
6 O 0
% O 0
) O 0
, O 0
thyroid B-Disease 0
function I-Disease 0
abnormalities I-Disease 0
( O 0
6 O 0
% O 0
) O 0
and O 0
pulmonary B-Disease 0
interstitial I-Disease 0
infiltrates I-Disease 0
( O 0
5 O 0
% O 0
) O 0
. O 0

Although O 0
large O 0
- O 0
dose O 0
amiodarone B-Chemical 0
is O 0
highly O 0
effective O 0
in O 0
the O 0
long O 0
- O 0
term O 0
treatment O 0
of O 0
VT B-Disease 0
or O 0
VF B-Disease 0
refractory O 0
to O 0
conventional O 0
antiarrhythmic O 0
drugs O 0
, O 0
it O 0
causes O 0
significant O 0
toxicity B-Disease 0
in O 0
approximately O 0
50 O 0
% O 0
of O 0
patients O 0
. O 0

However O 0
, O 0
when O 0
the O 0
dose O 0
is O 0
adjusted O 0
based O 0
on O 0
clinical O 0
response O 0
or O 0
the O 0
development O 0
of O 0
adverse O 0
effects O 0
, O 0
75 O 0
% O 0
of O 0
patients O 0
with O 0
VT B-Disease 0
or O 0
VF B-Disease 0
can O 0
be O 0
successfully O 0
managed O 0
with O 0
amiodarone B-Chemical 0
. O 0

Why O 0
may O 0
epsilon B-Chemical 0
- I-Chemical 0
aminocaproic I-Chemical 0
acid I-Chemical 0
( O 0
EACA B-Chemical 0
) O 0
induce O 0
myopathy B-Disease 0
in O 0
man O 0
? O 0

Report O 0
of O 0
a O 0
case O 0
and O 0
literature O 0
review O 0
. O 0

A O 0
case O 0
of O 0
necrotizing B-Disease 0
myopathy I-Disease 0
due O 0
to O 0
a O 0
short O 0
epsilon B-Chemical 0
- I-Chemical 0
aminocaproic I-Chemical 0
acid I-Chemical 0
( O 0
EACA B-Chemical 0
) O 0
treatment O 0
in O 0
a O 0
72 O 0
year O 0
- O 0
old O 0
patient O 0
with O 0
subarachnoid B-Disease 0
haemorrhage I-Disease 0
( O 0
SAH B-Disease 0
) O 0
is O 0
described O 0
. O 0

Pathogenetic O 0
hypotheses O 0
are O 0
discussed O 0
. O 0

Cerebral B-Disease 0
hemorrhage I-Disease 0
associated O 0
with O 0
phenylpropanolamine B-Chemical 0
in O 0
combination O 0
with O 0
caffeine B-Chemical 0
. O 0

Phenylpropanolamine B-Chemical 0
( O 0
PPA B-Chemical 0
) O 0
is O 0
a O 0
drug O 0
that O 0
has O 0
been O 0
associated O 0
with O 0
serious O 0
side O 0
effects O 0
including O 0
stroke B-Disease 0
. O 0

It O 0
is O 0
often O 0
combined O 0
with O 0
caffeine B-Chemical 0
in O 0
diet O 0
preparations O 0
and O 0
" O 0
look O 0
- O 0
alike O 0
" O 0
pills O 0
. O 0

In O 0
order O 0
to O 0
determine O 0
if O 0
PPA B-Chemical 0
/ O 0
caffeine B-Chemical 0
can O 0
lead O 0
to O 0
stroke B-Disease 0
in O 0
normotensive O 0
and O 0
/ O 0
or O 0
hypertensive B-Disease 0
rats O 0
, O 0
we O 0
administered O 0
the O 0
combination O 0
in O 0
six O 0
times O 0
the O 0
allowed O 0
human O 0
dose O 0
calculated O 0
on O 0
a O 0
per O 0
weight O 0
basis O 0
for O 0
the O 0
rats O 0
two O 0
times O 0
per O 0
day O 0
for O 0
five O 0
days O 0
. O 0

Subarachnoid B-Disease 0
and I-Disease 0
cerebral I-Disease 0
hemorrhage I-Disease 0
was O 0
noted O 0
in O 0
18 O 0
% O 0
of O 0
the O 0
hypertensive B-Disease 0
rats O 0
. O 0

A O 0
single O 0
PPA B-Chemical 0
/ O 0
caffeine B-Chemical 0
administration O 0
( O 0
same O 0
dose O 0
) O 0
lead O 0
to O 0
acute O 0
hypertension B-Disease 0
in O 0
both O 0
the O 0
normotensive O 0
and O 0
hypertensive B-Disease 0
animals O 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
PPA B-Chemical 0
/ O 0
caffeine B-Chemical 0
can O 0
lead O 0
to O 0
cerebral B-Disease 0
hemorrhage I-Disease 0
in O 0
previously O 0
hypertensive B-Disease 0
animals O 0
when O 0
administered O 0
in O 0
greater O 0
than O 0
the O 0
allowed O 0
dosage O 0
. O 0

An O 0
acute O 0
elevation O 0
in O 0
blood O 0
pressure O 0
may O 0
be O 0
a O 0
contributing O 0
factor O 0
. O 0

Renal B-Disease 0
papillary I-Disease 0
necrosis I-Disease 0
due O 0
to O 0
naproxen B-Chemical 0
. O 0

A O 0
31 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
, O 0
who O 0
had O 0
previously O 0
been O 0
treated O 0
with O 0
sulindac B-Chemical 0
, O 0
fenoprofen B-Chemical 0
calcium I-Chemical 0
, O 0
high O 0
dose O 0
salicylates B-Chemical 0
and O 0
gold B-Chemical 0
salts O 0
, O 0
developed O 0
renal B-Disease 0
papillary I-Disease 0
necrosis I-Disease 0
( O 0
RPN B-Disease 0
) O 0
4 O 0
months O 0
after O 0
institution O 0
of O 0
naproxen B-Chemical 0
therapy O 0
. O 0

No O 0
other O 0
factor O 0
predisposing O 0
to O 0
RPN B-Disease 0
could O 0
be O 0
discovered O 0
. O 0

Sulindac B-Chemical 0
was O 0
substituted O 0
for O 0
naproxen B-Chemical 0
and O 0
no O 0
further O 0
adverse O 0
renal O 0
effects O 0
occurred O 0
over O 0
the O 0
next O 0
12 O 0
months O 0
. O 0

We O 0
review O 0
previous O 0
reports O 0
linking O 0
RPN B-Disease 0
to O 0
antiinflammatory O 0
drug O 0
use O 0
and O 0
discuss O 0
possible O 0
advantages O 0
of O 0
sulindac B-Chemical 0
in O 0
patients O 0
who O 0
have O 0
experienced O 0
renal B-Disease 0
toxicity I-Disease 0
from O 0
other O 0
antiinflammatory O 0
agents O 0
. O 0

Nephrotoxic B-Disease 0
effects O 0
of O 0
aminoglycoside B-Chemical 0
treatment O 0
on O 0
renal O 0
protein O 0
reabsorption O 0
and O 0
accumulation O 0
. O 0

To O 0
quantify O 0
the O 0
effects O 0
of O 0
gentamicin B-Chemical 0
, O 0
kanamycin B-Chemical 0
and O 0
netilmicin B-Chemical 0
on O 0
renal O 0
protein O 0
reabsorption O 0
and O 0
accumulation O 0
, O 0
these O 0
drugs O 0
were O 0
administered O 0
to O 0
rats O 0
intraperitoneally O 0
( O 0
30 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
) O 0
for O 0
7 O 0
, O 0
14 O 0
or O 0
21 O 0
days O 0
. O 0

Scanning O 0
electron O 0
microscopy O 0
of O 0
the O 0
glomerular O 0
endothelia O 0
, O 0
urinary O 0
measurements O 0
of O 0
sodium B-Chemical 0
, O 0
potassium B-Chemical 0
, O 0
endogenous O 0
lysozyme O 0
, 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
as O 0
well O 0
as O 0
clearance O 0
and O 0
accumulation O 0
experiments O 0
after O 0
i O 0
. O 0
v O 0
. O 0
administration O 0
of O 0
egg O 0
- O 0
white O 0
lysozyme O 0
and O 0
measurements O 0
of O 0
inulin O 0
clearance O 0
( O 0
GFR O 0
) O 0
were O 0
done O 0
in O 0
each O 0
treatment O 0
group O 0
. O 0

Gentamicin B-Chemical 0
administration O 0
decreased O 0
diameter O 0
, O 0
density O 0
and O 0
shape O 0
of O 0
endothelial O 0
fenestrae O 0
. O 0

Kanamycin B-Chemical 0
and O 0
netilmicin B-Chemical 0
appeared O 0
to O 0
have O 0
no O 0
effect O 0
at O 0
the O 0
dose O 0
used O 0
. O 0

All O 0
three O 0
aminoglycosides B-Chemical 0
decreased O 0
GFR O 0
and O 0
increased O 0
urinary O 0
excretion O 0
of O 0
sodium B-Chemical 0
and O 0
potassium B-Chemical 0
. O 0

While O 0
gentamicin B-Chemical 0
and O 0
kanamycin B-Chemical 0
decreased O 0
the O 0
percentage O 0
reabsorption O 0
and O 0
accumulation O 0
of O 0
lysozyme O 0
after O 0
i O 0
. O 0
v O 0
. O 0
administration O 0
of O 0
egg O 0
- O 0
white O 0
lysozyme O 0
netilmicin B-Chemical 0
had O 0
no O 0
effect O 0
. O 0

Daily O 0
excretion O 0
of O 0
total O 0
protein O 0
, O 0
endogenous O 0
lysozyme O 0
and O 0
NAG O 0
increased O 0
only O 0
after O 0
treatment O 0
with O 0
kanamycin B-Chemical 0
and O 0
gentamicin B-Chemical 0
. O 0

Thus O 0
, O 0
aminoglycosides B-Chemical 0
may O 0
act O 0
as O 0
nephrotoxicants O 0
at O 0
glomerular O 0
and O 0
/ O 0
or O 0
tubular O 0
level O 0
inducing O 0
impairment B-Disease 0
of I-Disease 0
renal I-Disease 0
reabsorption I-Disease 0
and O 0
accumulation O 0
of O 0
proteins O 0
. O 0

Induction O 0
of O 0
the O 0
obstructive B-Disease 0
sleep I-Disease 0
apnea I-Disease 0
syndrome I-Disease 0
in O 0
a O 0
woman O 0
by O 0
exogenous O 0
androgen B-Chemical 0
administration O 0
. O 0

We O 0
documented O 0
airway O 0
occlusion O 0
during O 0
sleep O 0
and O 0
an O 0
abnormally O 0
high O 0
supraglottic O 0
resistance O 0
while O 0
awake O 0
in O 0
a O 0
54 O 0
- O 0
yr O 0
- O 0
old O 0
woman O 0
who O 0
had O 0
developed O 0
physical O 0
changes O 0
and O 0
the O 0
syndrome B-Disease 0
of I-Disease 0
obstructive I-Disease 0
sleep I-Disease 0
apnea I-Disease 0
while O 0
being O 0
administered O 0
exogenous O 0
androgens B-Chemical 0
. O 0

When O 0
the O 0
androgens B-Chemical 0
were O 0
withdrawn O 0
, O 0
the O 0
patient O 0
' O 0
s O 0
physical O 0
changes O 0
, O 0
symptoms O 0
, O 0
sleep O 0
study O 0
, O 0
and O 0
supraglottic O 0
resistance O 0
all O 0
returned O 0
to O 0
normal O 0
. O 0

A O 0
rechallenge O 0
with O 0
androgen B-Chemical 0
produced O 0
symptoms O 0
of O 0
obstructive B-Disease 0
sleep I-Disease 0
apnea I-Disease 0
that O 0
abated O 0
upon O 0
withdrawal O 0
of O 0
the O 0
hormone O 0
. O 0

Previous O 0
reports O 0
have O 0
favored O 0
a O 0
role O 0
of O 0
androgens B-Chemical 0
in O 0
the O 0
pathogenesis O 0
of O 0
sleep B-Disease 0
apnea I-Disease 0
. O 0

Our O 0
report O 0
provides O 0
direct O 0
evidence O 0
for O 0
this O 0
role O 0
. O 0

Structural O 0
and O 0
functional O 0
measurements O 0
indicate O 0
that O 0
androgens B-Chemical 0
exert O 0
a O 0
permissive O 0
or O 0
necessary O 0
action O 0
on O 0
the O 0
structural O 0
configuration O 0
of O 0
the O 0
oropharynx O 0
that O 0
predisposes O 0
to O 0
obstruction O 0
during O 0
sleep O 0
. O 0

Development O 0
of O 0
the O 0
obstructive B-Disease 0
sleep I-Disease 0
apnea I-Disease 0
syndrome I-Disease 0
must O 0
be O 0
considered O 0
a O 0
possible O 0
side O 0
effect O 0
of O 0
androgen B-Chemical 0
therapy O 0
. O 0

Cardiotoxic B-Disease 0
and O 0
possible O 0
leukemogenic O 0
effects O 0
of O 0
adriamycin B-Chemical 0
in O 0
nonhuman O 0
primates O 0
. O 0

10 O 0
monkeys O 0
( O 0
macaques O 0
) O 0
received O 0
adriamycin B-Chemical 0
by O 0
monthly O 0
intravenous O 0
injections O 0
at O 0
12 O 0
mg O 0
/ O 0
m2 O 0
( O 0
1 O 0
mg O 0
/ O 0
kg O 0
) O 0
. O 0

8 O 0
of O 0
the O 0
10 O 0
monkeys O 0
developed O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
at O 0
an O 0
average O 0
cumulative O 0
adriamycin B-Chemical 0
dose O 0
( O 0
310 O 0
mg O 0
/ O 0
m2 O 0
) O 0
well O 0
below O 0
that O 0
considered O 0
the O 0
safe O 0
upper O 0
limit O 0
( O 0
550 O 0
mg O 0
/ O 0
m2 O 0
) O 0
in O 0
man O 0
. O 0

Histologically O 0
, O 0
the O 0
myocardial B-Disease 0
lesions I-Disease 0
resembled O 0
those O 0
found O 0
in O 0
human O 0
anthracycline B-Chemical 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
. O 0

1 O 0
of O 0
the O 0
10 O 0
monkeys O 0
developed O 0
acute B-Disease 0
myeloblastic I-Disease 0
leukemia I-Disease 0
after O 0
receiving O 0
324 O 0
mg O 0
/ O 0
m2 O 0
of O 0
adriamycin B-Chemical 0
; O 0
the O 0
10th O 0
monkey O 0
is O 0
alive O 0
and O 0
well O 0
26 O 0
months O 0
after O 0
the O 0
last O 0
dose O 0
of O 0
drug O 0
. O 0

Our O 0
results O 0
suggest O 0
that O 0
adriamycin B-Chemical 0
is O 0
a O 0
more O 0
potent O 0
cardiotoxin O 0
in O 0
monkeys O 0
than O 0
in O 0
man O 0
, O 0
and O 0
that O 0
leukemia B-Disease 0
may O 0
be O 0
a O 0
consequence O 0
of O 0
prolonged O 0
treatment O 0
with O 0
this O 0
drug O 0
. O 0

Tricuspid B-Disease 0
valve I-Disease 0
regurgitation I-Disease 0
and O 0
lithium B-Chemical 0
carbonate I-Chemical 0
toxicity B-Disease 0
in O 0
a O 0
newborn O 0
infant O 0
. O 0

A O 0
newborn O 0
with O 0
massive O 0
tricuspid B-Disease 0
regurgitation I-Disease 0
, O 0
atrial B-Disease 0
flutter I-Disease 0
, O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
, O 0
and O 0
a O 0
high O 0
serum O 0
lithium B-Chemical 0
level O 0
is O 0
described O 0
. O 0

This O 0
is O 0
the O 0
first O 0
patient O 0
to O 0
initially O 0
manifest O 0
tricuspid B-Disease 0
regurgitation I-Disease 0
and O 0
atrial B-Disease 0
flutter I-Disease 0
, O 0
and O 0
the O 0
11th O 0
described O 0
patient O 0
with O 0
cardiac B-Disease 0
disease I-Disease 0
among O 0
infants O 0
exposed O 0
to O 0
lithium B-Chemical 0
compounds O 0
in O 0
the O 0
first O 0
trimester O 0
of O 0
pregnancy O 0
. O 0

Sixty O 0
- O 0
three O 0
percent O 0
of O 0
these O 0
infants O 0
had O 0
tricuspid O 0
valve O 0
involvement O 0
. O 0

Lithium B-Chemical 0
carbonate I-Chemical 0
may O 0
be O 0
a O 0
factor O 0
in O 0
the O 0
increasing O 0
incidence O 0
of O 0
congenital B-Disease 0
heart I-Disease 0
disease I-Disease 0
when O 0
taken O 0
during O 0
early O 0
pregnancy O 0
. O 0

It O 0
also O 0
causes O 0
neurologic B-Disease 0
depression I-Disease 0
, O 0
cyanosis B-Disease 0
, O 0
and O 0
cardiac B-Disease 0
arrhythmia I-Disease 0
when O 0
consumed O 0
prior O 0
to O 0
delivery O 0
. O 0

Effects O 0
of O 0
the O 0
novel O 0
compound O 0
aniracetam B-Chemical 0
( O 0
Ro B-Chemical 0
13 I-Chemical 0
- I-Chemical 0
5057 I-Chemical 0
) O 0
upon O 0
impaired B-Disease 0
learning I-Disease 0
and I-Disease 0
memory I-Disease 0
in O 0
rodents O 0
. O 0

The O 0
effect O 0
of O 0
aniracetam B-Chemical 0
( O 0
Ro B-Chemical 0
13 I-Chemical 0
- I-Chemical 0
5057 I-Chemical 0
, O 0
1 B-Chemical 0
- I-Chemical 0
anisoyl I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
pyrrolidinone I-Chemical 0
) O 0
was O 0
studied O 0
on O 0
various O 0
forms O 0
of O 0
experimentally O 0
impaired B-Disease 0
cognitive I-Disease 0
functions I-Disease 0
( O 0
learning O 0
and O 0
memory O 0
) O 0
in O 0
rodents O 0
and O 0
produced O 0
the O 0
following O 0
effects O 0
: O 0
( O 0
1 O 0
) O 0
almost O 0
complete O 0
prevention O 0
of O 0
the O 0
incapacity O 0
to O 0
learn O 0
a O 0
discrete O 0
escape O 0
response O 0
in O 0
rats O 0
exposed O 0
to O 0
sublethal O 0
hypercapnia B-Disease 0
immediately O 0
before O 0
the O 0
acquisition O 0
session O 0
; O 0
( O 0
2 O 0
) O 0
partial O 0
( O 0
rats O 0
) O 0
or O 0
complete O 0
( O 0
mice O 0
) O 0
prevention O 0
of O 0
the O 0
scopolamine B-Chemical 0
- O 0
induced O 0
short O 0
- O 0
term O 0
amnesia B-Disease 0
for O 0
a O 0
passive O 0
avoidance O 0
task O 0
; O 0
( O 0
3 O 0
) O 0
complete O 0
protection O 0
against O 0
amnesia B-Disease 0
for O 0
a O 0
passive O 0
avoidance O 0
task O 0
in O 0
rats O 0
submitted O 0
to O 0
electroconvulsive O 0
shock O 0
immediately O 0
after O 0
avoidance O 0
acquisition O 0
; O 0
( O 0
4 O 0
) O 0
prevention O 0
of O 0
the O 0
long O 0
- O 0
term O 0
retention O 0
- O 0
or O 0
retrieval O 0
- O 0
deficit O 0
for O 0
a O 0
passive O 0
avoidance O 0
task O 0
induced O 0
in O 0
rats O 0
and O 0
mice O 0
by O 0
chloramphenicol B-Chemical 0
or O 0
cycloheximide B-Chemical 0
administered O 0
immediately O 0
after O 0
acquisition O 0
; O 0
( O 0
5 O 0
) O 0
reversal O 0
, O 0
when O 0
administered O 0
as O 0
late O 0
as O 0
1 O 0
h O 0
before O 0
the O 0
retention O 0
test O 0
, O 0
of O 0
the O 0
deficit O 0
in O 0
retention O 0
or O 0
retrieval O 0
of O 0
a O 0
passive O 0
avoidance O 0
task O 0
induced O 0
by O 0
cycloheximide B-Chemical 0
injected O 0
2 O 0
days O 0
previously O 0
; O 0
( O 0
6 O 0
) O 0
prevention O 0
of O 0
the O 0
deficit O 0
in O 0
the O 0
retrieval O 0
of O 0
an O 0
active O 0
avoidance O 0
task O 0
induced O 0
in O 0
mice O 0
by O 0
subconvulsant O 0
electroshock O 0
or O 0
hypercapnia B-Disease 0
applied O 0
immediately O 0
before O 0
retrieval O 0
testing O 0
( O 0
24 O 0
h O 0
after O 0
acquisition O 0
) O 0
. O 0

These O 0
improvements O 0
or O 0
normalizations O 0
of O 0
impaired B-Disease 0
cognitive I-Disease 0
functions I-Disease 0
were O 0
seen O 0
at O 0
oral O 0
aniracetam B-Chemical 0
doses O 0
of O 0
10 O 0
- O 0
100 O 0
mg O 0
/ O 0
kg O 0
. O 0

Generally O 0
, O 0
the O 0
dose O 0
- O 0
response O 0
curves O 0
were O 0
bell O 0
- O 0
shaped O 0
. O 0

The O 0
mechanisms O 0
underlying O 0
the O 0
activity O 0
of O 0
aniracetam B-Chemical 0
and O 0
its O 0
' O 0
therapeutic O 0
window O 0
' O 0
are O 0
unknown O 0
. O 0

Piracetam B-Chemical 0
, O 0
another O 0
pyrrolidinone B-Chemical 0
derivative O 0
was O 0
used O 0
for O 0
comparison O 0
. O 0

It O 0
was O 0
active O 0
only O 0
in O 0
six O 0
of O 0
nine O 0
tests O 0
and O 0
had O 0
about O 0
one O 0
- O 0
tenth O 0
the O 0
potency O 0
of O 0
aniracetam B-Chemical 0
. O 0

The O 0
results O 0
indicate O 0
that O 0
aniracetam B-Chemical 0
improves O 0
cognitive O 0
functions O 0
which O 0
are O 0
impaired O 0
by O 0
different O 0
procedure O 0
and O 0
in O 0
different O 0
phases O 0
of O 0
the O 0
learning O 0
and O 0
memory O 0
process O 0
. O 0

Effect O 0
of O 0
calcium B-Chemical 0
chloride I-Chemical 0
on O 0
gross O 0
behavioural O 0
changes O 0
produced O 0
by O 0
carbachol B-Chemical 0
and O 0
eserine B-Chemical 0
in O 0
cats O 0
. O 0

The O 0
effect O 0
of O 0
calcium B-Chemical 0
chloride I-Chemical 0
injected O 0
into O 0
the O 0
cerebral O 0
ventricles O 0
of O 0
group O 0
- O 0
housed O 0
unanaesthetized O 0
cats O 0
upon O 0
vocalization O 0
( O 0
rage O 0
, O 0
hissing O 0
and O 0
snarling O 0
) O 0
, O 0
fighting O 0
( O 0
attack O 0
with O 0
paws O 0
and O 0
claws O 0
, O 0
defense O 0
with O 0
paws O 0
and O 0
claws O 0
and O 0
biting O 0
) O 0
, O 0
mydriasis B-Disease 0
, O 0
tremor B-Disease 0
and O 0
clonic B-Disease 0
- I-Disease 0
tonic I-Disease 0
convulsions I-Disease 0
produced O 0
by O 0
carbachol B-Chemical 0
and O 0
eserine B-Chemical 0
injected O 0
similarly O 0
was O 0
investigated O 0
. O 0

Calcium B-Chemical 0
chloride I-Chemical 0
depressed O 0
or O 0
almost O 0
completely O 0
abolished O 0
the O 0
vocalization O 0
and O 0
fighting O 0
due O 0
to O 0
carbachol B-Chemical 0
and O 0
eserine B-Chemical 0
. O 0

On O 0
the O 0
other O 0
hand O 0
, O 0
mydriasis B-Disease 0
, O 0
tremor B-Disease 0
and O 0
clonic B-Disease 0
- I-Disease 0
tonic I-Disease 0
convulsions I-Disease 0
evoked O 0
by O 0
carbachol B-Chemical 0
and O 0
eserine B-Chemical 0
were O 0
not O 0
significantly O 0
changed O 0
by O 0
calcium B-Chemical 0
chloride I-Chemical 0
. O 0

It O 0
is O 0
apparent O 0
that O 0
calcium B-Chemical 0
chloride I-Chemical 0
can O 0
" O 0
dissociate O 0
" O 0
vocalization O 0
and O 0
fighting O 0
from O 0
autonomic O 0
and O 0
motor O 0
phenomena O 0
such O 0
as O 0
mydriasis B-Disease 0
, O 0
tremor B-Disease 0
and O 0
clonic B-Disease 0
- I-Disease 0
tonic I-Disease 0
convulsions I-Disease 0
caused O 0
by O 0
carbachol B-Chemical 0
and O 0
eserine B-Chemical 0
. O 0

Calcium B-Chemical 0
chloride I-Chemical 0
inhibited O 0
the O 0
vocalization O 0
and O 0
fighting O 0
produced O 0
by O 0
carbachol B-Chemical 0
and O 0
eserine B-Chemical 0
most O 0
probably O 0
by O 0
a O 0
nonspecific O 0
stabilizing O 0
action O 0
on O 0
central O 0
muscarinic O 0
cholinoceptive O 0
sites O 0
. O 0

These O 0
results O 0
further O 0
support O 0
the O 0
view O 0
that O 0
calcium B-Chemical 0
ions O 0
in O 0
excess O 0
have O 0
an O 0
atropine B-Chemical 0
- O 0
like O 0
action O 0
also O 0
in O 0
the O 0
central O 0
nervous O 0
system O 0
. O 0

Thiazide B-Chemical 0
diuretics O 0
, O 0
hypokalemia B-Disease 0
and O 0
cardiac B-Disease 0
arrhythmias I-Disease 0
. O 0

Thiazide B-Chemical 0
diuretics O 0
are O 0
widely O 0
accepted O 0
as O 0
the O 0
cornerstone O 0
of O 0
antihypertensive O 0
treatment O 0
programs O 0
. O 0

Hypokalemia B-Disease 0
is O 0
a O 0
commonly O 0
encountered O 0
metabolic O 0
consequence O 0
of O 0
chronic O 0
thiazide B-Chemical 0
therapy O 0
. O 0

We O 0
treated O 0
38 O 0
patients O 0
( O 0
22 O 0
low O 0
renin O 0
, O 0
16 O 0
normal O 0
renin O 0
) O 0
with O 0
moderate O 0
diastolic B-Disease 0
hypertension I-Disease 0
with O 0
hydrochlorothiazide B-Chemical 0
( O 0
HCTC B-Chemical 0
) O 0
administered O 0
on O 0
a O 0
twice O 0
daily O 0
schedule O 0
. O 0

Initial O 0
dose O 0
was O 0
50 O 0
mg O 0
and O 0
the O 0
dose O 0
was O 0
increased O 0
at O 0
monthly O 0
intervals O 0
to O 0
100 O 0
mg O 0
, O 0
150 O 0
mg O 0
and O 0
200 O 0
mg O 0
daily O 0
until O 0
blood O 0
pressure O 0
normalized O 0
. O 0

The O 0
serum O 0
K B-Chemical 0
during O 0
the O 0
control O 0
period O 0
was O 0
4 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
mEq O 0
/ O 0
l O 0
an O 0
on O 0
50 O 0
, O 0
100 O 0
, O 0
150 O 0
and O 0
200 O 0
mg O 0
HCTZ B-Chemical 0
daily O 0
3 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
3 O 0
, O 0
3 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
, O 0
2 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
, O 0
and O 0
2 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
3 O 0
mEq O 0
/ O 0
l O 0
, O 0
respectively O 0
. O 0

Corresponding O 0
figures O 0
for O 0
whole O 0
body O 0
K B-Chemical 0
were O 0
4107 O 0
+ O 0
/ O 0
- O 0
208 O 0
, O 0
3722 O 0
+ O 0
/ O 0
- O 0
319 O 0
, O 0
3628 O 0
+ O 0
/ O 0
- O 0
257 O 0
, O 0
3551 O 0
+ O 0
/ O 0
- O 0
336 O 0
, O 0
and O 0
3269 O 0
+ O 0
/ O 0
- O 0
380 O 0
mEq O 0
, O 0
respectively O 0
. O 0

In O 0
13 O 0
patients O 0
we O 0
observed O 0
the O 0
effects O 0
of O 0
HCTZ B-Chemical 0
therapy O 0
( O 0
100 O 0
mg O 0
daily O 0
) O 0
on O 0
the O 0
occurrence O 0
of O 0
PVC O 0
' O 0
s O 0
during O 0
rest O 0
as O 0
well O 0
as O 0
during O 0
static O 0
and O 0
dynamic O 0
exercise O 0
. O 0

During O 0
rest O 0
we O 0
observed O 0
0 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
08 O 0
PVC O 0
beats O 0
/ O 0
min O 0
+ O 0
/ O 0
- O 0
SEM O 0
and O 0
during O 0
static O 0
and O 0
dynamic O 0
exercise O 0
0 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
06 O 0
and O 0
0 O 0
. O 0
8 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
15 O 0
, O 0
respectively O 0
. O 0

Corresponding O 0
figures O 0
during O 0
HCTZ B-Chemical 0
therapy O 0
100 O 0
mg O 0
daily O 0
were O 0
1 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
1 O 0
, O 0
3 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
7 O 0
and O 0
5 O 0
. O 0
7 O 0
4 O 0
/ O 0
- O 0
0 O 0
. O 0
8 O 0
, O 0
respectively O 0
. O 0

The O 0
occurrence O 0
of O 0
PVC O 0
' O 0
s O 0
correlated O 0
significantly O 0
with O 0
the O 0
fall O 0
in O 0
serum O 0
K B-Chemical 0
+ O 0
observed O 0
r O 0
= O 0
0 O 0
. O 0
72 O 0
, O 0
p O 0
less O 0
than O 0
0 O 0
. O 0
001 O 0
. O 0

In O 0
conclusion O 0
we O 0
found O 0
that O 0
thiazide B-Chemical 0
diuretics O 0
cause O 0
hypokalemia B-Disease 0
and O 0
depletion O 0
of O 0
body O 0
potassium B-Chemical 0
. O 0

The O 0
more O 0
profound O 0
hypokalemia B-Disease 0
, O 0
the O 0
greater O 0
the O 0
propensity O 0
for O 0
the O 0
occurrence O 0
of O 0
PVC O 0
' O 0
s O 0
. O 0

Circulating O 0
lysosomal O 0
enzymes O 0
and O 0
acute B-Disease 0
hepatic I-Disease 0
necrosis I-Disease 0
. O 0

The O 0
activities O 0
of O 0
the O 0
lysosomal O 0
enzymes O 0
acid O 0
and O 0
neutral O 0
protease O 0
, O 0
N O 0
- O 0
acetylglucosaminidase O 0
, O 0
and O 0
acid O 0
phosphatase O 0
were O 0
measured O 0
in O 0
the O 0
serum O 0
of O 0
patients O 0
with O 0
fulminant B-Disease 0
hepatic I-Disease 0
failure I-Disease 0
. O 0

Acid O 0
protease O 0
( O 0
cathepsin O 0
D O 0
) O 0
activity O 0
was O 0
increased O 0
about O 0
tenfold O 0
in O 0
patients O 0
who O 0
died O 0
and O 0
nearly O 0
fourfold O 0
in O 0
those O 0
who O 0
survived O 0
fulminant B-Disease 0
hepatic I-Disease 0
failure I-Disease 0
after O 0
paracetamol B-Chemical 0
overdose B-Disease 0
, O 0
whereas O 0
activities O 0
were O 0
increased O 0
equally O 0
in O 0
patients O 0
with O 0
fulminant B-Disease 0
hepatic I-Disease 0
failure I-Disease 0
due O 0
to O 0
viral B-Disease 0
hepatitis I-Disease 0
whether O 0
or O 0
not O 0
they O 0
survived O 0
. O 0

A O 0
correlation O 0
was O 0
found O 0
between O 0
serum O 0
acid O 0
protease O 0
activity O 0
and O 0
prothrombin O 0
time O 0
, O 0
and O 0
the O 0
increase O 0
in O 0
cathepsin O 0
D O 0
activity O 0
was O 0
sustained O 0
over O 0
several O 0
days O 0
compared O 0
with O 0
aspartate B-Chemical 0
aminotransferase O 0
, O 0
which O 0
showed O 0
a O 0
sharp O 0
early O 0
peak O 0
and O 0
then O 0
a O 0
fall O 0
. O 0

Circulating O 0
lysosomal O 0
proteases O 0
can O 0
damage O 0
other O 0
organs O 0
, O 0
and O 0
measurement O 0
of O 0
their O 0
activity O 0
may O 0
therefore O 0
be O 0
of O 0
added O 0
value O 0
in O 0
assessing O 0
prognosis O 0
in O 0
this O 0
condition O 0
. O 0

Hepatic B-Disease 0
veno I-Disease 0
- I-Disease 0
occlusive I-Disease 0
disease I-Disease 0
caused O 0
by O 0
6 B-Chemical 0
- I-Chemical 0
thioguanine I-Chemical 0
. O 0

Clinically O 0
reversible O 0
veno B-Disease 0
- I-Disease 0
occlusive I-Disease 0
disease I-Disease 0
of I-Disease 0
the I-Disease 0
liver I-Disease 0
developed O 0
in O 0
a O 0
23 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
acute B-Disease 0
lymphocytic I-Disease 0
leukemia I-Disease 0
after O 0
10 O 0
months O 0
of O 0
maintenance O 0
therapy O 0
with O 0
6 B-Chemical 0
- I-Chemical 0
thioguanine I-Chemical 0
. O 0

Serial O 0
liver O 0
biopsies O 0
showed O 0
the O 0
development O 0
and O 0
resolution O 0
of O 0
intense O 0
sinusoidal O 0
engorgement O 0
. O 0

Although O 0
this O 0
disease O 0
was O 0
clinically O 0
reversible O 0
, O 0
some O 0
subintimal O 0
fibrosis B-Disease 0
about O 0
the O 0
terminal O 0
hepatic O 0
veins O 0
persisted O 0
. O 0

This O 0
case O 0
presented O 0
a O 0
unique O 0
opportunity O 0
to O 0
observe O 0
the O 0
histologic O 0
features O 0
of O 0
clinically O 0
reversible O 0
hepatic B-Disease 0
veno I-Disease 0
- I-Disease 0
occlusive I-Disease 0
disease I-Disease 0
over O 0
time O 0
, O 0
and O 0
may O 0
be O 0
the O 0
first O 0
case O 0
of O 0
veno O 0
- O 0
occlusive O 0
related O 0
solely O 0
to O 0
6 B-Chemical 0
- I-Chemical 0
thioguanine I-Chemical 0
. O 0

Chlorpropamide B-Chemical 0
- O 0
induced O 0
optic B-Disease 0
neuropathy I-Disease 0
. O 0

A O 0
65 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
adult B-Disease 0
- I-Disease 0
onset I-Disease 0
diabetes I-Disease 0
treated O 0
with O 0
chlorpropamide B-Chemical 0
( O 0
Diabenese B-Chemical 0
) O 0
had O 0
a O 0
toxic B-Disease 0
optic I-Disease 0
neuropathy I-Disease 0
that O 0
resolved O 0
with O 0
discontinuation O 0
of O 0
chlorpropamide B-Chemical 0
therapy O 0
. O 0

Visual B-Disease 0
loss I-Disease 0
occurs O 0
in O 0
diabetics B-Disease 0
for O 0
a O 0
variety O 0
of O 0
reasons O 0
, O 0
and O 0
accurate O 0
diagnosis O 0
is O 0
necessary O 0
to O 0
institute O 0
appropriate O 0
therapy O 0
. O 0

The O 0
possibility O 0
of O 0
a O 0
drug O 0
- O 0
induced O 0
optic B-Disease 0
neuropathy I-Disease 0
should O 0
be O 0
considered O 0
in O 0
the O 0
differential O 0
diagnosis O 0
of O 0
visual B-Disease 0
loss I-Disease 0
in O 0
diabetics B-Disease 0
. O 0

Plasma O 0
and O 0
urinary O 0
lipids O 0
and O 0
lipoproteins O 0
during O 0
the O 0
development O 0
of O 0
nephrotic B-Disease 0
syndrome I-Disease 0
induced O 0
in O 0
the O 0
rat O 0
by O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
. O 0

This O 0
study O 0
was O 0
undertaken O 0
to O 0
ascertain O 0
whether O 0
the O 0
alterations O 0
of O 0
plasma O 0
lipoproteins O 0
found O 0
in O 0
nephrotic B-Disease 0
syndrome I-Disease 0
induced O 0
by O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
were O 0
due O 0
to O 0
nephrotic B-Disease 0
syndrome I-Disease 0
per O 0
se O 0
, O 0
or O 0
, O 0
at O 0
least O 0
in O 0
part O 0
, O 0
to O 0
the O 0
aminonucleoside B-Chemical 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
the O 0
changes O 0
in O 0
plasma O 0
and O 0
urinary O 0
lipoproteins O 0
during O 0
the O 0
administration O 0
of O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
( O 0
20 O 0
mg O 0
/ O 0
kg O 0
for O 0
7 O 0
days O 0
) O 0
and O 0
the O 0
subsequent O 0
development O 0
of O 0
nephrotic B-Disease 0
syndrome I-Disease 0
. O 0

Since O 0
massive O 0
albuminuria B-Disease 0
occurred O 0
after O 0
6 O 0
days O 0
of O 0
treatment O 0
, O 0
the O 0
time O 0
- O 0
course O 0
study O 0
was O 0
divided O 0
into O 0
two O 0
stages O 0
: O 0
pre O 0
- O 0
nephrotic B-Disease 0
stage O 0
( O 0
day O 0
1 O 0
- O 0
5 O 0
) O 0
and O 0
nephrotic B-Disease 0
stage O 0
( O 0
day O 0
6 O 0
- O 0
11 O 0
) O 0
. O 0

In O 0
pre O 0
- O 0
nephrotic B-Disease 0
stage O 0
the O 0
plasma O 0
level O 0
of O 0
fatty B-Chemical 0
acids I-Chemical 0
, O 0
triacylglycerol B-Chemical 0
and O 0
VLDL O 0
decreased O 0
while O 0
that O 0
of O 0
phospholipid O 0
, O 0
cholesteryl B-Chemical 0
esters I-Chemical 0
and O 0
HDL O 0
remained O 0
constant O 0
. O 0

Plasma O 0
apolipoprotein O 0
A O 0
- O 0
I O 0
tended O 0
to O 0
increase O 0
( O 0
40 O 0
% O 0
increase O 0
at O 0
day O 0
5 O 0
) O 0
. O 0

At O 0
the O 0
beginning O 0
of O 0
nephrotic B-Disease 0
stage O 0
( O 0
day O 0
6 O 0
) O 0
the O 0
concentration O 0
of O 0
plasma O 0
albumin O 0
dropped O 0
to O 0
a O 0
very O 0
low O 0
level O 0
, O 0
while O 0
that O 0
of O 0
apolipoprotein O 0
A O 0
- O 0
I O 0
increased O 0
abruptly O 0
( O 0
4 O 0
- O 0
fold O 0
increase O 0
) O 0
and O 0
continued O 0
to O 0
rise O 0
, O 0
although O 0
less O 0
steeply O 0
, O 0
in O 0
the O 0
following O 0
days O 0
. O 0

The O 0
plasma O 0
concentration O 0
of O 0
HDL O 0
followed O 0
the O 0
same O 0
pattern O 0
. O 0

Plasma O 0
VLDL O 0
and O 0
LDL O 0
increased O 0
at O 0
a O 0
later O 0
stage O 0
( O 0
day O 0
9 O 0
) O 0
. O 0

Plasma O 0
apolipoprotein O 0
A O 0
- O 0
I O 0
was O 0
found O 0
not O 0
only O 0
in O 0
HDL O 0
( O 0
1 O 0
. O 0
063 O 0
- O 0
1 O 0
. O 0
210 O 0
g O 0
/ O 0
ml O 0
) O 0
but O 0
also O 0
in O 0
the O 0
LDL O 0
density O 0
class O 0
( O 0
1 O 0
. O 0
025 O 0
- O 0
1 O 0
. O 0
050 O 0
g O 0
/ O 0
ml O 0
) O 0
. O 0

In O 0
the O 0
pre O 0
- O 0
nephrotic B-Disease 0
stage O 0
lipoproteinuria O 0
was O 0
negligible O 0
, O 0
while O 0
in O 0
the O 0
early O 0
nephrotic B-Disease 0
stage O 0
the O 0
urinary O 0
loss O 0
of O 0
plasma O 0
lipoproteins O 0
consisted O 0
mainly O 0
of O 0
HDL O 0
. O 0

These O 0
observations O 0
indicate O 0
that O 0
puromycin B-Chemical 0
aminonucleoside I-Chemical 0
alters O 0
plasma O 0
lipoproteins O 0
by O 0
lowering O 0
VLDL O 0
and O 0
increasing O 0
HDL O 0
. O 0

It O 0
is O 0
likely O 0
that O 0
the O 0
early O 0
and O 0
striking O 0
increase O 0
of O 0
plasma O 0
HDL O 0
found O 0
in O 0
nephrotic B-Disease 0
rats O 0
is O 0
related O 0
to O 0
a O 0
direct O 0
effect O 0
of O 0
the O 0
drug O 0
on O 0
HDL O 0
metabolism O 0
. O 0

Fatal O 0
aplastic B-Disease 0
anemia I-Disease 0
following O 0
topical O 0
administration O 0
of O 0
ophthalmic O 0
chloramphenicol B-Chemical 0
. O 0

A O 0
73 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
died O 0
of O 0
aplastic B-Disease 0
anemia I-Disease 0
less O 0
than O 0
two O 0
months O 0
after O 0
undergoing O 0
cataract B-Disease 0
extraction O 0
and O 0
beginning O 0
topical O 0
therapy O 0
with O 0
chloramphenicol B-Chemical 0
. O 0

The O 0
first O 0
signs O 0
of O 0
pancytopenia B-Disease 0
began O 0
within O 0
one O 0
month O 0
of O 0
the O 0
surgery O 0
. O 0

The O 0
pattern O 0
of O 0
the O 0
aplastic B-Disease 0
anemia I-Disease 0
was O 0
associated O 0
with O 0
an O 0
idiosyncratic O 0
response O 0
to O 0
chloramphenicol B-Chemical 0
. O 0

This O 0
was O 0
the O 0
second O 0
report O 0
of O 0
fatal O 0
aplastic B-Disease 0
anemia I-Disease 0
after O 0
topical O 0
treatment O 0
with O 0
chloramphenicol B-Chemical 0
for O 0
ocular O 0
conditions O 0
, O 0
although O 0
two O 0
cases O 0
of O 0
reversible O 0
bone B-Disease 0
marrow I-Disease 0
hypoplasia I-Disease 0
have O 0
also O 0
been O 0
reported O 0
. O 0

Any O 0
other O 0
suspected O 0
cases O 0
of O 0
ocular B-Disease 0
toxicity I-Disease 0
associated O 0
with O 0
topically O 0
applied O 0
chloramphenicol B-Chemical 0
should O 0
be O 0
reported O 0
to O 0
the O 0
National O 0
Registry O 0
of O 0
Drug O 0
- O 0
Induced O 0
Ocular O 0
Side O 0
Effects O 0
, O 0
Oregon O 0
Health O 0
Sciences O 0
University O 0
, O 0
Portland O 0
, O 0
OR O 0
97201 O 0
. O 0

Midazolam B-Chemical 0
compared O 0
with O 0
thiopentone B-Chemical 0
as O 0
an O 0
induction O 0
agent O 0
. O 0

In O 0
patients O 0
premedicated O 0
with O 0
scopolamine B-Chemical 0
+ O 0
morphine B-Chemical 0
( O 0
+ O 0
5 O 0
mg O 0
nitrazepam B-Chemical 0
the O 0
evening O 0
before O 0
surgery O 0
) O 0
, O 0
the O 0
sleep O 0
- O 0
inducing O 0
effect O 0
of O 0
midazolam B-Chemical 0
0 O 0
. O 0
15 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
was O 0
clearly O 0
slower O 0
in O 0
onset O 0
than O 0
that O 0
of O 0
thiopentone B-Chemical 0
4 O 0
. O 0
67 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
v O 0
. O 0
Somewhat O 0
fewer O 0
cardiovascular O 0
and O 0
local O 0
sequelae O 0
were O 0
found O 0
in O 0
the O 0
midazolam B-Chemical 0
group O 0
, O 0
but O 0
, O 0
although O 0
apnoea B-Disease 0
occurred O 0
less O 0
often O 0
in O 0
the O 0
midazolam B-Chemical 0
group O 0
it O 0
lasted O 0
longer O 0
. O 0

On O 0
the O 0
whole O 0
, O 0
the O 0
differences O 0
between O 0
midazolam B-Chemical 0
and O 0
thiopentone B-Chemical 0
had O 0
no O 0
apparent O 0
clinical O 0
consequences O 0
. O 0

Midazolam B-Chemical 0
is O 0
a O 0
new O 0
alternative O 0
agent O 0
for O 0
induction O 0
in O 0
combination O 0
anaesthesia O 0
. O 0

Extrapyramidal O 0
side O 0
effects O 0
and O 0
oral O 0
haloperidol B-Chemical 0
: O 0
an O 0
analysis O 0
of O 0
explanatory O 0
patient O 0
and O 0
treatment O 0
characteristics O 0
. O 0

The O 0
incidence O 0
of O 0
extrapyramidal O 0
side O 0
effects O 0
( O 0
EPS O 0
) O 0
was O 0
evaluated O 0
in O 0
98 O 0
patients O 0
treated O 0
with O 0
haloperidol B-Chemical 0
. O 0

The O 0
incidence O 0
of O 0
parkinsonism B-Disease 0
was O 0
higher O 0
at O 0
higher O 0
doses O 0
of O 0
haloperidol B-Chemical 0
and O 0
in O 0
younger O 0
patients O 0
. O 0

Prophylactic O 0
antiparkinsonian O 0
medication O 0
was O 0
effective O 0
in O 0
younger O 0
but O 0
not O 0
in O 0
older O 0
patients O 0
. O 0

However O 0
, O 0
these O 0
medications O 0
were O 0
more O 0
effective O 0
in O 0
both O 0
young O 0
and O 0
old O 0
patients O 0
when O 0
given O 0
after O 0
parkinsonism B-Disease 0
developed O 0
. O 0

Akathisia B-Disease 0
was O 0
controlled O 0
by O 0
the O 0
benzodiazepine B-Chemical 0
lorazepam B-Chemical 0
in O 0
14 O 0
out O 0
of O 0
16 O 0
patients O 0
, O 0
while O 0
prophylactic O 0
antiparkinsonians O 0
were O 0
ineffective O 0
. O 0

The O 0
present O 0
study O 0
points O 0
to O 0
patient O 0
characteristics O 0
that O 0
may O 0
be O 0
of O 0
significance O 0
in O 0
the O 0
development O 0
of O 0
EPS O 0
due O 0
to O 0
haloperidol B-Chemical 0
. O 0

Deaths O 0
from O 0
local O 0
anesthetic O 0
- O 0
induced O 0
convulsions B-Disease 0
in O 0
mice O 0
. O 0

Median O 0
convulsant O 0
( O 0
CD50 O 0
) O 0
and O 0
median O 0
lethal O 0
( O 0
LD50 O 0
) O 0
doses O 0
of O 0
three O 0
representative O 0
local O 0
anesthetics O 0
were O 0
determined O 0
in O 0
adult O 0
mice O 0
to O 0
evaluate O 0
the O 0
threat O 0
to O 0
life O 0
of O 0
local O 0
anesthetic O 0
- O 0
induced O 0
convulsions B-Disease 0
. O 0

The O 0
CD50 O 0
and O 0
LD50 O 0
, O 0
respectively O 0
, O 0
were O 0
57 O 0
. O 0
7 O 0
and O 0
58 O 0
. O 0
7 O 0
mg O 0
/ O 0
kg O 0
for O 0
bupivacaine B-Chemical 0
, O 0
111 O 0
. O 0
0 O 0
and O 0
133 O 0
. O 0
1 O 0
mg O 0
/ O 0
kg O 0
for O 0
lidocaine B-Chemical 0
, O 0
and O 0
243 O 0
. O 0
4 O 0
and O 0
266 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
for O 0
chloroprocaine B-Chemical 0
. O 0

When O 0
given O 0
intraperitoneally O 0
, O 0
bupivacaine B-Chemical 0
thus O 0
was O 0
only O 0
about O 0
twice O 0
as O 0
toxic O 0
as O 0
lidocaine B-Chemical 0
and O 0
four O 0
times O 0
as O 0
toxic O 0
as O 0
chloroprocaine B-Chemical 0
. O 0

Convulsions B-Disease 0
always O 0
preceded O 0
death O 0
, O 0
except O 0
after O 0
precipitous O 0
cardiopulmonary B-Disease 0
arrest I-Disease 0
from O 0
extreme O 0
doses O 0
. O 0

A O 0
CD50 O 0
dose O 0
of O 0
local O 0
anesthetic O 0
( O 0
causing O 0
convulsions B-Disease 0
in O 0
50 O 0
% O 0
of O 0
mice O 0
) O 0
was O 0
fatal O 0
in O 0
90 O 0
% O 0
of O 0
bupivacaine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
, O 0
in O 0
57 O 0
% O 0
of O 0
the O 0
chloroprocaine B-Chemical 0
group O 0
, O 0
and O 0
in O 0
6 O 0
% O 0
of O 0
the O 0
lidocaine B-Chemical 0
group O 0
. O 0

The O 0
narrow O 0
gap O 0
between O 0
convulsant O 0
and O 0
lethal O 0
doses O 0
of O 0
local O 0
anesthetics O 0
indicates O 0
that O 0
untreated O 0
convulsions B-Disease 0
present O 0
much O 0
more O 0
of O 0
a O 0
threat O 0
to O 0
life O 0
than O 0
heretofore O 0
appreciated O 0
. O 0

REM B-Disease 0
sleep I-Disease 0
deprivation I-Disease 0
changes O 0
behavioral O 0
response O 0
to O 0
catecholaminergic O 0
and O 0
serotonergic O 0
receptor O 0
activation O 0
in O 0
rats O 0
. O 0

The O 0
effects O 0
of O 0
REM B-Disease 0
sleep I-Disease 0
deprivation I-Disease 0
( O 0
REMD B-Disease 0
) O 0
on O 0
apomorphine B-Chemical 0
- O 0
induced O 0
aggressiveness B-Disease 0
and O 0
quipazine B-Chemical 0
- O 0
induced O 0
head B-Disease 0
twitches I-Disease 0
in O 0
rats O 0
were O 0
determined O 0
. O 0

Forty O 0
- O 0
eight O 0
hr O 0
of O 0
REMD B-Disease 0
increased O 0
apomorphine B-Chemical 0
- O 0
induced O 0
aggressiveness B-Disease 0
, O 0
and O 0
reduced O 0
( O 0
immediately O 0
after O 0
completing O 0
of O 0
REMD B-Disease 0
) O 0
or O 0
increased O 0
( O 0
96 O 0
hr O 0
after O 0
completing O 0
of O 0
REMD B-Disease 0
) O 0
quipazine B-Chemical 0
- O 0
induced O 0
head B-Disease 0
twitches I-Disease 0
. O 0

Results O 0
are O 0
discussed O 0
in O 0
terms O 0
of O 0
similarity O 0
to O 0
pharmacological O 0
effects O 0
of O 0
other O 0
antidepressive O 0
treatments O 0
. O 0

Fatal O 0
aplastic B-Disease 0
anemia I-Disease 0
due O 0
to O 0
indomethacin B-Chemical 0
- O 0
- O 0
lymphocyte O 0
transformation O 0
tests O 0
in O 0
vitro O 0
. O 0

Although O 0
indomethacin B-Chemical 0
has O 0
been O 0
implicated O 0
as O 0
a O 0
possible O 0
cause O 0
of O 0
aplastic B-Disease 0
anemia I-Disease 0
on O 0
the O 0
basis O 0
of O 0
a O 0
few O 0
clinical O 0
observations O 0
, O 0
its O 0
role O 0
has O 0
not O 0
been O 0
definitely O 0
established O 0
. O 0

A O 0
case O 0
of O 0
fatal O 0
aplastic B-Disease 0
anemia I-Disease 0
is O 0
described O 0
in O 0
which O 0
no O 0
drugs O 0
other O 0
than O 0
allopurinol B-Chemical 0
and O 0
indomethacin B-Chemical 0
were O 0
given O 0
. O 0

Indomethacin B-Chemical 0
was O 0
first O 0
given O 0
four O 0
weeks O 0
prior O 0
to O 0
the O 0
onset O 0
of O 0
symptoms O 0
. O 0

A O 0
positive O 0
lymphocyte O 0
transformation O 0
test O 0
with O 0
indomethacin B-Chemical 0
in O 0
vitro O 0
further O 0
substantiates O 0
the O 0
potential O 0
role O 0
of O 0
this O 0
drug O 0
in O 0
causing O 0
aplastic B-Disease 0
anemia I-Disease 0
in O 0
a O 0
susceptible O 0
patient O 0
. O 0

Fortunately O 0
, O 0
this O 0
seems O 0
to O 0
be O 0
a O 0
very O 0
rare O 0
complication O 0
. O 0

Dose O 0
- O 0
effect O 0
and O 0
structure O 0
- O 0
function O 0
relationships O 0
in O 0
doxorubicin B-Chemical 0
cardiomyopathy B-Disease 0
. O 0

The O 0
cardiomyopathy B-Disease 0
( O 0
CM B-Disease 0
) O 0
produced O 0
by O 0
the O 0
anticancer O 0
drug O 0
doxorubicin B-Chemical 0
( O 0
DXR B-Chemical 0
) O 0
( O 0
Adriamycin B-Chemical 0
) O 0
provides O 0
a O 0
unique O 0
opportunity O 0
to O 0
analyze O 0
dose O 0
- O 0
effect O 0
and O 0
structure O 0
- O 0
function O 0
relationships O 0
during O 0
development O 0
of O 0
myocardial B-Disease 0
disease I-Disease 0
. O 0

We O 0
measured O 0
the O 0
degree O 0
of O 0
morphologic O 0
damage O 0
by O 0
ultrastructural O 0
examination O 0
of O 0
endomyocardial O 0
biopsy O 0
and O 0
the O 0
degree O 0
of O 0
performance O 0
abnormally O 0
by O 0
right O 0
heart O 0
catheterization O 0
in O 0
patients O 0
receiving O 0
DXR B-Chemical 0
. O 0

Morphologic O 0
damage O 0
was O 0
variable O 0
but O 0
was O 0
proportional O 0
to O 0
the O 0
total O 0
cumulative O 0
DXR B-Chemical 0
dose O 0
between O 0
100 O 0
and O 0
600 O 0
mg O 0
/ O 0
m2 O 0
. O 0

Performance O 0
abnormalities O 0
correlated O 0
weakly O 0
with O 0
dose O 0
, O 0
exhibited O 0
a O 0
curvilinear O 0
relationship O 0
, O 0
and O 0
had O 0
a O 0
" O 0
threshold O 0
" O 0
for O 0
expression O 0
. O 0

Catheterization O 0
abnormalities O 0
correlated O 0
well O 0
with O 0
morphologic O 0
damage O 0
( O 0
r O 0
= O 0
0 O 0
. O 0
57 O 0
to O 0
0 O 0
. O 0
78 O 0
) O 0
in O 0
a O 0
subgroup O 0
of O 0
patients O 0
in O 0
whom O 0
exercise O 0
hemodynamics O 0
were O 0
measured O 0
, O 0
and O 0
this O 0
relationship O 0
also O 0
exhibited O 0
a O 0
curvilinear O 0
, O 0
threshold O 0
configuration O 0
. O 0

In O 0
DXR B-Chemical 0
- O 0
CM B-Disease 0
myocardial B-Disease 0
damage I-Disease 0
is O 0
proportional O 0
to O 0
the O 0
degree O 0
of O 0
cytotoxic O 0
insult O 0
( O 0
DXR B-Chemical 0
dose O 0
) O 0
while O 0
myocardial O 0
function O 0
is O 0
preserved O 0
until O 0
a O 0
critical O 0
dose O 0
or O 0
degree O 0
of O 0
damage O 0
is O 0
reached O 0
, O 0
after O 0
which O 0
myocardial O 0
performance O 0
deteriorates O 0
rapidly O 0
. O 0

Massive O 0
cerebral B-Disease 0
edema I-Disease 0
associated O 0
with O 0
fulminant O 0
hepatic B-Disease 0
failure I-Disease 0
in O 0
acetaminophen B-Chemical 0
overdose B-Disease 0
: O 0
possible O 0
role O 0
of O 0
cranial O 0
decompression O 0
. O 0

Cerebral B-Disease 0
edema I-Disease 0
may O 0
complicate O 0
the O 0
course O 0
of O 0
fulminant B-Disease 0
hepatic I-Disease 0
failure I-Disease 0
. O 0

Response O 0
to O 0
conventional O 0
therapy O 0
has O 0
been O 0
disappointing O 0
. O 0

We O 0
present O 0
a O 0
patient O 0
with O 0
fatal O 0
acetaminophen B-Chemical 0
- O 0
induced O 0
fulminant B-Disease 0
hepatic I-Disease 0
failure I-Disease 0
, O 0
with O 0
signs O 0
and O 0
symptoms O 0
of O 0
cerebral B-Disease 0
edema I-Disease 0
, O 0
unresponsive O 0
to O 0
conventional O 0
medical O 0
therapy O 0
. O 0

Cranial O 0
decompression O 0
was O 0
carried O 0
out O 0
. O 0

A O 0
justification O 0
of O 0
the O 0
need O 0
for O 0
further O 0
evaluation O 0
of O 0
cranial O 0
decompression O 0
in O 0
such O 0
patients O 0
is O 0
presented O 0
. O 0

Subjective O 0
assessment O 0
of O 0
sexual B-Disease 0
dysfunction I-Disease 0
of O 0
patients O 0
on O 0
long O 0
- O 0
term O 0
administration O 0
of O 0
digoxin B-Chemical 0
. O 0

Various O 0
data O 0
suggest O 0
that O 0
male O 0
patients O 0
who O 0
have O 0
received O 0
digoxin B-Chemical 0
on O 0
a O 0
longterm O 0
basis O 0
have O 0
increased O 0
levels O 0
of O 0
serum O 0
estrogen B-Chemical 0
and O 0
decreased O 0
levels O 0
of O 0
plasma O 0
testosterone B-Chemical 0
and O 0
luteinizing O 0
hormone O 0
( O 0
LH O 0
) O 0
. O 0

This O 0
study O 0
was O 0
undertaken O 0
to O 0
investigate O 0
the O 0
links O 0
between O 0
the O 0
long O 0
- O 0
term O 0
administration O 0
of O 0
digoxin B-Chemical 0
therapy O 0
and O 0
sexual O 0
behavior O 0
, O 0
and O 0
the O 0
effect O 0
of O 0
digoxin B-Chemical 0
on O 0
plasma O 0
levels O 0
of O 0
estradiol B-Chemical 0
, O 0
testosterone B-Chemical 0
, O 0
and O 0
LH O 0
. O 0

The O 0
patients O 0
of O 0
the O 0
study O 0
and O 0
control O 0
group O 0
( O 0
without O 0
digoxin B-Chemical 0
) O 0
were O 0
of O 0
similar O 0
cardiac O 0
functional O 0
capacity O 0
and O 0
age O 0
( O 0
25 O 0
- O 0
40 O 0
years O 0
) O 0
and O 0
were O 0
randomly O 0
selected O 0
from O 0
the O 0
rheumatic B-Disease 0
heart I-Disease 0
disease I-Disease 0
patients O 0
. O 0

A O 0
subjective O 0
assessment O 0
of O 0
sexual O 0
behavior O 0
in O 0
the O 0
study O 0
and O 0
control O 0
groups O 0
was O 0
carried O 0
out O 0
, O 0
using O 0
parameters O 0
such O 0
as O 0
sexual O 0
desire O 0
, O 0
sexual O 0
excitement O 0
, O 0
and O 0
frequency O 0
of O 0
sexual O 0
relations O 0
. O 0

Personal O 0
interviews O 0
and O 0
a O 0
questionnaire O 0
were O 0
also O 0
used O 0
for O 0
the O 0
evaluation O 0
of O 0
sexual O 0
behavior O 0
. O 0

The O 0
findings O 0
support O 0
the O 0
reports O 0
concerning O 0
digoxin B-Chemical 0
effect O 0
on O 0
plasma O 0
estradiol B-Chemical 0
, O 0
testosterone B-Chemical 0
, O 0
and O 0
LH O 0
. O 0

The O 0
differences O 0
in O 0
the O 0
means O 0
were O 0
significant O 0
. O 0

Tests O 0
used O 0
to O 0
evaluate O 0
the O 0
changes O 0
in O 0
sexual O 0
behavior O 0
showed O 0
a O 0
significant O 0
decrease B-Disease 0
in I-Disease 0
sexual I-Disease 0
desire I-Disease 0
, O 0
sexual O 0
excitement O 0
phase O 0
( O 0
erection O 0
) O 0
, O 0
and O 0
frequency O 0
of O 0
sexual O 0
relations O 0
in O 0
the O 0
study O 0
group O 0
. O 0

Endometrial B-Disease 0
carcinoma I-Disease 0
after O 0
Hodgkin B-Disease 0
disease I-Disease 0
in O 0
childhood O 0
. O 0

A O 0
34 O 0
- O 0
year O 0
- O 0
old O 0
patient O 0
developed O 0
metastic O 0
endometrial B-Disease 0
carcinoma I-Disease 0
after O 0
Hodgkin B-Disease 0
disease I-Disease 0
in O 0
childhood O 0
. O 0

She O 0
had O 0
ovarian B-Disease 0
failure I-Disease 0
after O 0
abdominal O 0
irradiation O 0
and O 0
chemotherapy O 0
for O 0
Hodgkin B-Disease 0
disease I-Disease 0
, O 0
and O 0
received O 0
exogenous O 0
estrogens B-Chemical 0
, O 0
a O 0
treatment O 0
implicated O 0
in O 0
the O 0
development O 0
of O 0
endometrial B-Disease 0
cancer I-Disease 0
in O 0
menopausal O 0
women O 0
. O 0

Young O 0
women O 0
on O 0
replacement O 0
estrogens B-Chemical 0
for O 0
ovarian B-Disease 0
failure I-Disease 0
after O 0
cancer B-Disease 0
therapy O 0
may O 0
also O 0
have O 0
increased O 0
risk O 0
of O 0
endometrial B-Disease 0
carcinoma I-Disease 0
and O 0
should O 0
be O 0
examined O 0
periodically O 0
. O 0

Long O 0
- O 0
term O 0
lithium B-Chemical 0
treatment O 0
and O 0
the O 0
kidney O 0
. O 0

Interim O 0
report O 0
on O 0
fifty O 0
patients O 0
. O 0

This O 0
is O 0
a O 0
report O 0
on O 0
the O 0
first O 0
part O 0
of O 0
our O 0
study O 0
of O 0
the O 0
effects O 0
of O 0
long O 0
- O 0
term O 0
lithium B-Chemical 0
treatment O 0
on O 0
the O 0
kidney O 0
. O 0

Creatinine B-Chemical 0
clearance O 0
, O 0
maximum O 0
urinary O 0
osmolality O 0
and O 0
24 O 0
hour O 0
urine O 0
volume O 0
have O 0
been O 0
tested O 0
in O 0
50 O 0
affectively O 0
ill O 0
patients O 0
who O 0
have O 0
been O 0
on O 0
long O 0
- O 0
term O 0
lithium B-Chemical 0
for O 0
more O 0
than O 0
one O 0
year O 0
. O 0

These O 0
findings O 0
have O 0
been O 0
compared O 0
with O 0
norms O 0
and O 0
with O 0
values O 0
of O 0
the O 0
same O 0
tests O 0
from O 0
screening O 0
prior O 0
to O 0
lithium B-Chemical 0
, O 0
available O 0
for O 0
most O 0
of O 0
our O 0
patients O 0
. O 0

No O 0
evidence O 0
was O 0
found O 0
for O 0
any O 0
reduction O 0
of O 0
glomerular O 0
filtration O 0
during O 0
lithium B-Chemical 0
treatment O 0
. O 0

Low O 0
clearance O 0
values O 0
found O 0
in O 0
several O 0
patients O 0
could O 0
be O 0
accounted O 0
for O 0
by O 0
their O 0
age O 0
and O 0
their O 0
pre O 0
- O 0
lithium B-Chemical 0
values O 0
. O 0

Urinary O 0
concentration O 0
defect O 0
appeared O 0
frequent O 0
but O 0
the O 0
extent O 0
of O 0
the O 0
impairment O 0
is O 0
difficult O 0
to O 0
assess O 0
because O 0
of O 0
the O 0
uncertainty O 0
about O 0
the O 0
norms O 0
applicable O 0
to O 0
this O 0
group O 0
of O 0
patients O 0
. O 0

The O 0
concentration O 0
defect O 0
appeared O 0
reversible O 0
, O 0
at O 0
least O 0
in O 0
part O 0
. O 0

Polyuria B-Disease 0
above O 0
3 O 0
litres O 0
/ O 0
24 O 0
hours O 0
was O 0
found O 0
in O 0
10 O 0
% O 0
of O 0
patients O 0
. O 0

An O 0
attempt O 0
is O 0
made O 0
to O 0
draw O 0
practical O 0
conclusions O 0
from O 0
the O 0
preliminary O 0
findings O 0
. O 0

Nephrotoxicity B-Disease 0
of O 0
cyclosporin B-Chemical 0
A I-Chemical 0
and O 0
FK506 B-Chemical 0
: O 0
inhibition O 0
of O 0
calcineurin O 0
phosphatase O 0
. O 0

Cyclosporin B-Chemical 0
A I-Chemical 0
( O 0
CsA B-Chemical 0
; O 0
50 O 0
mg O 0
/ O 0
kg O 0
) O 0
and O 0
Fujimycine B-Chemical 0
( O 0
FK506 B-Chemical 0
; O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
but O 0
not O 0
the O 0
related O 0
macrolide B-Chemical 0
immunosuppressant O 0
rapamycin B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
, O 0
caused O 0
a O 0
reduction O 0
of O 0
glomerular O 0
filtration O 0
rate O 0
, O 0
degenerative O 0
changes O 0
of O 0
proximal O 0
tubular O 0
epithelium O 0
, O 0
and O 0
hypertrophy B-Disease 0
of O 0
the O 0
juxtaglomerular O 0
apparatus O 0
in O 0
male O 0
Wistar O 0
rats O 0
when O 0
given O 0
for O 0
10 O 0
days O 0
. O 0

The O 0
molecular O 0
mechanisms O 0
of O 0
CsA B-Chemical 0
and O 0
FK506 B-Chemical 0
toxicity B-Disease 0
were O 0
investigated O 0
. O 0

Cyclophilin O 0
A O 0
and O 0
FK506 B-Chemical 0
- O 0
binding O 0
protein O 0
, O 0
the O 0
main O 0
intracytoplasmic O 0
receptors O 0
for O 0
CsA B-Chemical 0
and O 0
FK506 B-Chemical 0
, O 0
respectively O 0
, O 0
were O 0
each O 0
detected O 0
in O 0
renal O 0
tissue O 0
extract O 0
. O 0

In O 0
the O 0
kidney O 0
, O 0
high O 0
levels O 0
of O 0
immunoreactive O 0
and O 0
enzymatically O 0
active O 0
calcineurin O 0
were O 0
found O 0
which O 0
were O 0
inhibited O 0
by O 0
the O 0
immunosuppressants O 0
CsA B-Chemical 0
and O 0
FK506 B-Chemical 0
, O 0
but O 0
not O 0
by O 0
rapamycin B-Chemical 0
. O 0

Finally O 0
, O 0
specific O 0
immunophilin O 0
- O 0
drug O 0
- O 0
calcineurin O 0
complexes O 0
formed O 0
only O 0
in O 0
the O 0
presence O 0
of O 0
CsA B-Chemical 0
and O 0
FK506 B-Chemical 0
, O 0
but O 0
not O 0
rapamycin B-Chemical 0
. O 0

These O 0
results O 0
suggest O 0
that O 0
the O 0
nephrotoxic B-Disease 0
effects O 0
of O 0
CsA B-Chemical 0
and O 0
FK506 B-Chemical 0
is O 0
likely O 0
mediated O 0
through O 0
binding O 0
to O 0
renal O 0
immunophilin O 0
and O 0
inhibiting O 0
calcineurin O 0
phosphatase O 0
. O 0

Acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
in O 0
high O 0
dose O 0
carboplatin B-Chemical 0
chemotherapy O 0
. O 0

Carboplatin B-Chemical 0
has O 0
been O 0
reported O 0
to O 0
cause O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
when O 0
administered O 0
in O 0
high O 0
doses O 0
to O 0
adult O 0
patients O 0
. O 0

We O 0
report O 0
a O 0
4 O 0
1 O 0
/ O 0
2 O 0
- O 0
year O 0
- O 0
old O 0
girl O 0
who O 0
was O 0
treated O 0
with O 0
high O 0
- O 0
dose O 0
carboplatin B-Chemical 0
for O 0
metastatic O 0
parameningeal O 0
embryonal B-Disease 0
rhabdomyosarcoma I-Disease 0
. O 0

Acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
developed O 0
followed O 0
by O 0
a O 0
slow O 0
partial O 0
recovery O 0
of O 0
renal O 0
function O 0
. O 0

Possible O 0
contributing O 0
factors O 0
are O 0
discussed O 0
. O 0

Clinical O 0
evaluation O 0
on O 0
combined O 0
administration O 0
of O 0
oral O 0
prostacyclin B-Chemical 0
analogue O 0
beraprost B-Chemical 0
and O 0
phosphodiesterase O 0
inhibitor O 0
cilostazol B-Chemical 0
. O 0

Among O 0
various O 0
oral O 0
antiplatelets O 0
, O 0
a O 0
combination O 0
of O 0
a O 0
novel O 0
prostacyclin B-Chemical 0
analogue O 0
beraprost B-Chemical 0
( O 0
BPT B-Chemical 0
) O 0
and O 0
a O 0
potent O 0
phosphodiesterase O 0
inhibitor O 0
cilostazol B-Chemical 0
( O 0
CLZ B-Chemical 0
) O 0
may O 0
result O 0
in O 0
untoward O 0
clinical O 0
effects O 0
due O 0
to O 0
possible O 0
synergistic O 0
elevation O 0
of O 0
intracellular O 0
cAMP B-Chemical 0
( O 0
cyclic B-Chemical 0
adenosine I-Chemical 0
3 I-Chemical 0
' I-Chemical 0
, I-Chemical 0
5 I-Chemical 0
' I-Chemical 0
- I-Chemical 0
monophosphate I-Chemical 0
) O 0
. O 0

Thereby O 0
, O 0
a O 0
clinical O 0
study O 0
of O 0
the O 0
combined O 0
administration O 0
of O 0
the O 0
two O 0
agents O 0
was O 0
attempted O 0
. O 0

Twelve O 0
healthy O 0
volunteers O 0
were O 0
assigned O 0
to O 0
take O 0
BPT B-Chemical 0
/ O 0
CLZ B-Chemical 0
in O 0
the O 0
following O 0
schedule O 0
; O 0
BPT B-Chemical 0
: O 0
40 O 0
micrograms O 0
at O 0
day O 0
1 O 0
and O 0
120 O 0
micrograms O 0
t O 0
. O 0
i O 0
. O 0
d O 0
. O 0
from O 0
day O 0
7 O 0
to O 0
14 O 0
, O 0
CLZ B-Chemical 0
: O 0
200 O 0
mg O 0
t O 0
. O 0
i O 0
. O 0
d O 0
. O 0
from O 0
day O 0
3 O 0
to O 0
14 O 0
. O 0

At O 0
various O 0
time O 0
intervals O 0
, O 0
physical O 0
examination O 0
and O 0
blood O 0
collection O 0
for O 0
ex O 0
vivo O 0
platelet B-Disease 0
aggregation I-Disease 0
and O 0
determination O 0
of O 0
intraplatelet O 0
cAMP B-Chemical 0
were O 0
performed O 0
. O 0

Throughout O 0
the O 0
observation O 0
period O 0
, O 0
no O 0
significant O 0
alteration O 0
in O 0
vital O 0
signs O 0
was O 0
observed O 0
. O 0

Seven O 0
out O 0
of O 0
12 O 0
subjects O 0
experienced O 0
headache B-Disease 0
of O 0
a O 0
short O 0
duration O 0
accompanying O 0
facial B-Disease 0
flush I-Disease 0
in O 0
one O 0
and O 0
nausea B-Disease 0
in O 0
one O 0
, O 0
especially O 0
after O 0
ingestion O 0
of O 0
CLZ B-Chemical 0
. O 0

All O 0
of O 0
these O 0
symptoms O 0
, O 0
probably O 0
caused O 0
by O 0
the O 0
vasodilating O 0
effect O 0
of O 0
the O 0
two O 0
agents O 0
, O 0
were O 0
of O 0
mild O 0
degree O 0
and O 0
no O 0
special O 0
treatment O 0
was O 0
required O 0
. O 0

Intraplatelet O 0
cAMP B-Chemical 0
content O 0
was O 0
gradually O 0
but O 0
significantly O 0
increased O 0
to O 0
9 O 0
. O 0
84 O 0
+ O 0
/ O 0
- O 0
4 O 0
. O 0
59 O 0
pmol O 0
per O 0
10 O 0
( O 0
9 O 0
) O 0
platelets O 0
at O 0
day O 0
14 O 0
in O 0
comparison O 0
with O 0
the O 0
initial O 0
value O 0
( O 0
6 O 0
. O 0
87 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
25 O 0
pmol O 0
) O 0
. O 0

The O 0
platelet O 0
aggregability O 0
was O 0
significantly O 0
suppressed O 0
at O 0
various O 0
time O 0
intervals O 0
but O 0
no O 0
additive O 0
or O 0
synergistic O 0
inhibitory O 0
effect O 0
by O 0
the O 0
combined O 0
administration O 0
was O 0
noted O 0
. O 0

In O 0
conclusion O 0
, O 0
the O 0
combined O 0
administration O 0
of O 0
BPT B-Chemical 0
/ O 0
CLZ B-Chemical 0
is O 0
safe O 0
at O 0
doses O 0
used O 0
in O 0
the O 0
study O 0
, O 0
though O 0
the O 0
beneficial O 0
clinical O 0
effect O 0
of O 0
the O 0
combined O 0
administration O 0
has O 0
yet O 0
to O 0
be O 0
elucidated O 0
. O 0

Pravastatin B-Chemical 0
- O 0
associated O 0
myopathy B-Disease 0
. O 0

Report O 0
of O 0
a O 0
case O 0
. O 0

A O 0
case O 0
of O 0
acute O 0
inflammatory B-Disease 0
myopathy I-Disease 0
associated O 0
with O 0
the O 0
use O 0
of O 0
pravastatin B-Chemical 0
, O 0
a O 0
new O 0
hydrophilic O 0
3 O 0
- O 0
hydroxy O 0
- O 0
3 O 0
methylglutaril O 0
coenzyme O 0
A O 0
reductase O 0
inhibitor O 0
, O 0
is O 0
reported O 0
. O 0

The O 0
patient O 0
, O 0
a O 0
69 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
was O 0
affected O 0
by O 0
non B-Disease 0
- I-Disease 0
insulin I-Disease 0
- I-Disease 0
dependent I-Disease 0
diabetes I-Disease 0
mellitus I-Disease 0
and O 0
hypertension B-Disease 0
. O 0

He O 0
assumed O 0
pravastatin B-Chemical 0
( O 0
20 O 0
mg O 0
/ O 0
day O 0
) O 0
because O 0
of O 0
hypercholesterolemia B-Disease 0
. O 0

He O 0
was O 0
admitted O 0
with O 0
acute O 0
myopathy B-Disease 0
of O 0
the O 0
lower O 0
limbs O 0
which O 0
resolved O 0
in O 0
a O 0
few O 0
days O 0
after O 0
pravastatin B-Chemical 0
discontinuation O 0
. O 0

A O 0
previously O 0
unknown O 0
hypothyroidism B-Disease 0
, O 0
probably O 0
due O 0
to O 0
chronic O 0
autoimmune B-Disease 0
thyroiditis I-Disease 0
, O 0
was O 0
evidenced O 0
. O 0

Muscle O 0
biopsy O 0
( O 0
left O 0
gastrocnemius O 0
) O 0
revealed O 0
a O 0
perimysial O 0
and O 0
endomysial O 0
inflammatory O 0
infiltrate O 0
with O 0
a O 0
prevalence O 0
of O 0
CD4 O 0
+ O 0
lymphocytes O 0
. O 0

While O 0
lovastatin B-Chemical 0
and O 0
simvastatin B-Chemical 0
have O 0
been O 0
associated O 0
with O 0
toxic O 0
myopathy B-Disease 0
, O 0
pravastatin B-Chemical 0
- O 0
associated O 0
myopathy B-Disease 0
could O 0
represent O 0
a O 0
distinct O 0
, O 0
inflammatory O 0
entity O 0
. O 0

Reversal O 0
of O 0
ammonia B-Chemical 0
coma B-Disease 0
in O 0
rats O 0
by O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
: O 0
a O 0
peripheral O 0
effect O 0
. O 0

Ammonia B-Chemical 0
coma B-Disease 0
was O 0
produced O 0
in O 0
rats O 0
within O 0
10 O 0
to O 0
15 O 0
minutes O 0
of O 0
an O 0
intraperitonealinjection O 0
of O 0
1 O 0
. O 0
7 O 0
mmol O 0
NH4CL B-Chemical 0
. O 0

This O 0
coma B-Disease 0
was O 0
prevented O 0
with O 0
1 O 0
. O 0
68 O 0
mmol O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
given O 0
by O 0
gastric O 0
intubation O 0
15 O 0
minutes O 0
before O 0
the O 0
ammonium B-Chemical 0
salt I-Chemical 0
injection O 0
. O 0

The O 0
effect O 0
of O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
was O 0
correlated O 0
with O 0
a O 0
decrease O 0
in O 0
blood O 0
and O 0
brain O 0
ammonia B-Chemical 0
, O 0
an O 0
increase O 0
in O 0
brain O 0
dopamine B-Chemical 0
, O 0
and O 0
an O 0
increase O 0
in O 0
renal O 0
excretion O 0
of O 0
ammonia B-Chemical 0
and O 0
urea B-Chemical 0
. O 0

Intraventricular O 0
infusion O 0
of O 0
dopamine B-Chemical 0
sufficient O 0
to O 0
raise O 0
the O 0
brain O 0
dopamine B-Chemical 0
to O 0
the O 0
same O 0
extent O 0
did O 0
not O 0
prevent O 0
the O 0
ammonia B-Chemical 0
coma B-Disease 0
nor O 0
affect O 0
the O 0
blood O 0
and O 0
brain O 0
ammonia B-Chemical 0
concentrations O 0
. O 0

Bilateral O 0
nephrectomy O 0
eliminated O 0
the O 0
beneficial O 0
effect O 0
of O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
on O 0
blood O 0
and O 0
brain O 0
ammonia B-Chemical 0
and O 0
the O 0
ammonia B-Chemical 0
coma B-Disease 0
was O 0
not O 0
prevented O 0
. O 0

Thus O 0
, O 0
the O 0
reduction O 0
in O 0
blood O 0
and O 0
brain O 0
ammonia B-Chemical 0
and O 0
the O 0
prevention O 0
of O 0
ammonia B-Chemical 0
coma B-Disease 0
after O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
, O 0
can O 0
be O 0
accounted O 0
for O 0
by O 0
the O 0
peripheral O 0
effect O 0
of O 0
dopamine B-Chemical 0
on O 0
renal O 0
function O 0
rather O 0
than O 0
its O 0
central O 0
action O 0
. O 0

These O 0
results O 0
provide O 0
a O 0
reasonable O 0
explanation O 0
for O 0
the O 0
beneficial O 0
effects O 0
observed O 0
in O 0
some O 0
encephalopathic B-Disease 0
patients O 0
receiving O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
. O 0

Etoposide B-Chemical 0
- O 0
related O 0
myocardial B-Disease 0
infarction I-Disease 0
. O 0

The O 0
occurrence O 0
of O 0
a O 0
myocardial B-Disease 0
infarction I-Disease 0
is O 0
reported O 0
after O 0
chemotherapy O 0
containing O 0
etoposide B-Chemical 0
, O 0
in O 0
a O 0
man O 0
with O 0
no O 0
risk O 0
factors O 0
for O 0
coronary B-Disease 0
heart I-Disease 0
disease I-Disease 0
. O 0

Possible O 0
causal O 0
mechanisms O 0
are O 0
discussed O 0
. O 0

Halogenated O 0
anesthetics O 0
form O 0
liver O 0
adducts O 0
and O 0
antigens O 0
that O 0
cross O 0
- O 0
react O 0
with O 0
halothane B-Chemical 0
- O 0
induced O 0
antibodies O 0
. O 0

Two O 0
halogenated O 0
anesthetics O 0
, O 0
enflurane B-Chemical 0
and O 0
isoflurane B-Chemical 0
, O 0
have O 0
been O 0
associated O 0
with O 0
an O 0
allergic O 0
- O 0
type O 0
hepatic B-Disease 0
injury I-Disease 0
both O 0
alone O 0
and O 0
following O 0
previous O 0
exposure O 0
to O 0
halothane B-Chemical 0
. O 0

Halothane B-Chemical 0
hepatitis B-Disease 0
appears O 0
to O 0
involve O 0
an O 0
aberrant O 0
immune O 0
response O 0
. O 0

An O 0
antibody O 0
response O 0
to O 0
a O 0
protein O 0
- O 0
bound O 0
biotransformation O 0
product O 0
( O 0
trifluoroacetyl B-Chemical 0
adduct O 0
) O 0
has O 0
been O 0
detected O 0
on O 0
halothane B-Chemical 0
hepatitis B-Disease 0
patients O 0
. O 0

This O 0
study O 0
was O 0
performed O 0
to O 0
determine O 0
cross O 0
- O 0
reactivity O 0
between O 0
enflurane B-Chemical 0
and O 0
isoflurane B-Chemical 0
with O 0
the O 0
hypersensitivity B-Disease 0
induced O 0
by O 0
halothane B-Chemical 0
. O 0

The O 0
subcellular O 0
and O 0
lobular O 0
production O 0
of O 0
hepatic O 0
neoantigens O 0
recognized O 0
by O 0
halothane B-Chemical 0
- O 0
induced O 0
antibodies O 0
following O 0
enflurane B-Chemical 0
and O 0
isoflurane B-Chemical 0
, O 0
and O 0
the O 0
biochemical O 0
nature O 0
of O 0
these O 0
neoantigens O 0
was O 0
investigated O 0
in O 0
two O 0
animal O 0
models O 0
. O 0

Enflurane B-Chemical 0
administration O 0
resulted O 0
in O 0
neoantigens O 0
detected O 0
in O 0
both O 0
the O 0
microsomal O 0
and O 0
cytosolic O 0
fraction O 0
of O 0
liver O 0
homogenates O 0
and O 0
in O 0
the O 0
centrilobular O 0
region O 0
of O 0
the O 0
liver O 0
. O 0

In O 0
the O 0
same O 0
liver O 0
, O 0
biochemical O 0
analysis O 0
detected O 0
fluorinated O 0
liver O 0
adducts O 0
that O 0
were O 0
up O 0
to O 0
20 O 0
- O 0
fold O 0
greater O 0
in O 0
guinea O 0
pigs O 0
than O 0
in O 0
rats O 0
. O 0

This O 0
supports O 0
and O 0
extends O 0
previous O 0
evidence O 0
for O 0
a O 0
mechanism O 0
by O 0
which O 0
enflurane B-Chemical 0
and O 0
/ O 0
or O 0
isoflurane B-Chemical 0
could O 0
produce O 0
a O 0
hypersensitivity B-Disease 0
condition O 0
similar O 0
to O 0
that O 0
of O 0
halothane B-Chemical 0
hepatitis B-Disease 0
either O 0
alone O 0
or O 0
subsequent O 0
to O 0
halothane B-Chemical 0
administration O 0
. O 0

The O 0
guinea O 0
pig O 0
would O 0
appear O 0
to O 0
be O 0
a O 0
useful O 0
model O 0
for O 0
further O 0
investigations O 0
of O 0
the O 0
immunological O 0
response O 0
to O 0
these O 0
antigens O 0
. O 0

Cholinergic O 0
toxicity B-Disease 0
resulting O 0
from O 0
ocular O 0
instillation O 0
of O 0
echothiophate B-Chemical 0
iodide I-Chemical 0
eye O 0
drops O 0
. O 0

A O 0
patient O 0
developed O 0
a O 0
severe O 0
cholinergic O 0
syndrome O 0
from O 0
the O 0
use O 0
of O 0
echothiophate B-Chemical 0
iodide I-Chemical 0
ophthalmic O 0
drops O 0
, O 0
presented O 0
with O 0
profound O 0
muscle B-Disease 0
weakness I-Disease 0
and O 0
was O 0
initially O 0
given O 0
the O 0
diagnosis O 0
of O 0
myasthenia B-Disease 0
gravis I-Disease 0
. O 0

Red O 0
blood O 0
cell O 0
and O 0
serum O 0
cholinesterase O 0
levels O 0
were O 0
severely O 0
depressed O 0
and O 0
symptoms O 0
resolved O 0
spontaneously O 0
following O 0
discontinuation O 0
of O 0
the O 0
eye O 0
drops O 0
. O 0

Seizure B-Disease 0
after O 0
flumazenil B-Chemical 0
administration O 0
in O 0
a O 0
pediatric O 0
patient O 0
. O 0

Flumazenil B-Chemical 0
is O 0
a O 0
benzodiazepine B-Chemical 0
receptor O 0
antagonist O 0
used O 0
to O 0
reverse O 0
sedation O 0
and O 0
respiratory B-Disease 0
depression I-Disease 0
induced O 0
by O 0
benzodiazepines B-Chemical 0
. O 0

Seizures B-Disease 0
and O 0
cardiac B-Disease 0
arrhythmias I-Disease 0
have O 0
complicated O 0
its O 0
use O 0
in O 0
adult O 0
patients O 0
. O 0

Overdose B-Disease 0
patients O 0
who O 0
have O 0
coingested O 0
tricyclic O 0
antidepressants O 0
have O 0
a O 0
higher O 0
risk O 0
of O 0
these O 0
complications O 0
. O 0

Little O 0
information O 0
exists O 0
concerning O 0
adverse O 0
effects O 0
of O 0
flumazenil B-Chemical 0
in O 0
children O 0
. O 0

We O 0
report O 0
the O 0
occurrence O 0
of O 0
a O 0
generalized O 0
tonic B-Disease 0
- I-Disease 0
clonic I-Disease 0
seizure I-Disease 0
in O 0
a O 0
pediatric O 0
patient O 0
following O 0
the O 0
administration O 0
of O 0
flumazenil B-Chemical 0
. O 0

Phase O 0
I O 0
trial O 0
of O 0
13 B-Chemical 0
- I-Chemical 0
cis I-Chemical 0
- I-Chemical 0
retinoic I-Chemical 0
acid I-Chemical 0
in O 0
children O 0
with O 0
neuroblastoma B-Disease 0
following O 0
bone O 0
marrow O 0
transplantation O 0
. O 0

PURPOSE O 0
: O 0
Treatment O 0
of O 0
neuroblastoma B-Disease 0
cell O 0
lines O 0
with O 0
13 B-Chemical 0
- I-Chemical 0
cis I-Chemical 0
- I-Chemical 0
retinoic I-Chemical 0
acid I-Chemical 0
( O 0
cis B-Chemical 0
- I-Chemical 0
RA I-Chemical 0
) O 0
can O 0
cause O 0
sustained O 0
inhibition O 0
of O 0
proliferation O 0
. O 0

Since O 0
cis B-Chemical 0
- I-Chemical 0
RA I-Chemical 0
has O 0
demonstrated O 0
clinical O 0
responses O 0
in O 0
neuroblastoma B-Disease 0
patients O 0
, O 0
it O 0
may O 0
be O 0
effective O 0
in O 0
preventing O 0
relapse O 0
after O 0
cytotoxic O 0
therapy O 0
. O 0

This O 0
phase O 0
I O 0
trial O 0
was O 0
designed O 0
to O 0
determine O 0
the O 0
maximal O 0
- O 0
tolerated O 0
dosage O 0
( O 0
MTD O 0
) O 0
, O 0
toxicities B-Disease 0
, O 0
and O 0
pharmacokinetics O 0
of O 0
cis B-Chemical 0
- I-Chemical 0
RA I-Chemical 0
administered O 0
on O 0
an O 0
intermittent O 0
schedule O 0
in O 0
children O 0
with O 0
neuroblastoma B-Disease 0
following O 0
bone O 0
marrow O 0
transplantation O 0
( O 0
BMT O 0
) O 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
Fifty O 0
- O 0
one O 0
assessable O 0
patients O 0
, O 0
2 O 0
to O 0
12 O 0
years O 0
of O 0
age O 0
, O 0
were O 0
treated O 0
with O 0
oral O 0
cis B-Chemical 0
- I-Chemical 0
RA I-Chemical 0
administered O 0
in O 0
two O 0
equally O 0
divided O 0
doses O 0
daily O 0
for O 0
2 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
for O 0
up O 0
to O 0
12 O 0
courses O 0
. O 0

The O 0
dose O 0
was O 0
escalated O 0
from O 0
100 O 0
to O 0
200 O 0
mg O 0
/ O 0
m2 O 0
/ O 0
d O 0
until O 0
dose O 0
- O 0
limiting O 0
toxicity B-Disease 0
( O 0
DLT O 0
) O 0
was O 0
observed O 0
. O 0

A O 0
single O 0
intrapatient O 0
dose O 0
escalation O 0
was O 0
permitted O 0
. O 0

RESULTS O 0
: O 0
The O 0
MTD O 0
of O 0
cis B-Chemical 0
- I-Chemical 0
RA I-Chemical 0
was O 0
160 O 0
mg O 0
/ O 0
m2 O 0
/ O 0
d O 0
. O 0

Dose O 0
- O 0
limiting O 0
toxicities B-Disease 0
in O 0
six O 0
of O 0
nine O 0
patients O 0
at O 0
200 O 0
mg O 0
/ O 0
m2 O 0
/ O 0
d O 0
included O 0
hypercalcemia B-Disease 0
( O 0
n O 0
= O 0
3 O 0
) O 0
, O 0
rash B-Disease 0
( O 0
n O 0
= O 0
2 O 0
) O 0
, O 0
and O 0
anemia B-Disease 0
/ O 0
thrombocytopenia B-Disease 0
/ O 0
emesis B-Disease 0
/ O 0
rash B-Disease 0
( O 0
n O 0
= O 0
1 O 0
) O 0
. O 0

All O 0
toxicities B-Disease 0
resolved O 0
after O 0
cis B-Chemical 0
- I-Chemical 0
RA I-Chemical 0
was O 0
discontinued O 0
. O 0

Three O 0
complete O 0
responses O 0
were O 0
observed O 0
in O 0
marrow O 0
metastases B-Disease 0
. O 0

Serum O 0
levels O 0
of O 0
7 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
0 O 0
mumol O 0
/ O 0
L O 0
( O 0
peak O 0
) O 0
and O 0
4 O 0
. O 0
0 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
8 O 0
mumol O 0
/ O 0
L O 0
( O 0
trough O 0
) O 0
at O 0
the O 0
MTD O 0
were O 0
maintained O 0
during O 0
14 O 0
days O 0
of O 0
therapy O 0
. O 0

The O 0
DLT O 0
correlated O 0
with O 0
serum O 0
levels O 0
> O 0
or O 0
= O 0
10 O 0
mumol O 0
/ O 0
L O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
MTD O 0
of O 0
cis B-Chemical 0
- I-Chemical 0
RA I-Chemical 0
given O 0
on O 0
this O 0
intermittent O 0
schedule O 0
was O 0
160 O 0
mg O 0
/ O 0
m2 O 0
/ O 0
d O 0
. O 0

Serum O 0
levels O 0
known O 0
to O 0
be O 0
effective O 0
against O 0
neuroblastoma B-Disease 0
in O 0
vitro O 0
were O 0
achieved O 0
at O 0
this O 0
dose O 0
. O 0

The O 0
DLT O 0
included O 0
hypercalcemia B-Disease 0
, O 0
and O 0
may O 0
be O 0
predicted O 0
by O 0
serum O 0
cis B-Chemical 0
- I-Chemical 0
RA I-Chemical 0
levels O 0
. O 0

Monitoring O 0
of O 0
serum O 0
calcium B-Chemical 0
and O 0
cis B-Chemical 0
- I-Chemical 0
RA I-Chemical 0
levels O 0
is O 0
indicated O 0
in O 0
future O 0
trials O 0
. O 0

Time O 0
dependence O 0
of O 0
plasma O 0
malondialdehyde B-Chemical 0
, O 0
oxypurines B-Chemical 0
, O 0
and O 0
nucleosides B-Chemical 0
during O 0
incomplete O 0
cerebral B-Disease 0
ischemia I-Disease 0
in O 0
the O 0
rat O 0
. O 0

Incomplete O 0
cerebral B-Disease 0
ischemia I-Disease 0
( O 0
30 O 0
min O 0
) O 0
was O 0
induced O 0
in O 0
the O 0
rat O 0
by O 0
bilaterally O 0
clamping O 0
the O 0
common O 0
carotid O 0
arteries O 0
. O 0

Peripheral O 0
venous O 0
blood O 0
samples O 0
were O 0
withdrawn O 0
from O 0
the O 0
femoral O 0
vein O 0
four O 0
times O 0
( O 0
once O 0
every O 0
5 O 0
min O 0
) O 0
before O 0
ischemia B-Disease 0
( O 0
0 O 0
time O 0
) O 0
and O 0
5 O 0
, O 0
15 O 0
, O 0
and O 0
30 O 0
min O 0
after O 0
ischemia B-Disease 0
. O 0

Plasma O 0
extracts O 0
were O 0
analyzed O 0
by O 0
a O 0
highly O 0
sensitive O 0
high O 0
- O 0
performance O 0
liquid O 0
chromatographic O 0
method O 0
for O 0
the O 0
direct O 0
determination O 0
of O 0
malondialdehyde B-Chemical 0
, O 0
oxypurines B-Chemical 0
, O 0
and O 0
nucleosides B-Chemical 0
. O 0

During O 0
ischemia B-Disease 0
, O 0
a O 0
time O 0
- O 0
dependent O 0
increase O 0
of O 0
plasma O 0
oxypurines B-Chemical 0
and O 0
nucleosides B-Chemical 0
was O 0
observed O 0
. O 0

Plasma O 0
malondialdehyde B-Chemical 0
, O 0
which O 0
was O 0
present O 0
in O 0
minimal O 0
amount O 0
at O 0
zero O 0
time O 0
( O 0
0 O 0
. O 0
058 O 0
mumol O 0
/ O 0
liter O 0
plasma O 0
; O 0
SD O 0
0 O 0
. O 0
015 O 0
) O 0
, O 0
increased O 0
after O 0
5 O 0
min O 0
of O 0
ischemia B-Disease 0
, O 0
resulting O 0
in O 0
a O 0
fivefold O 0
increase O 0
after O 0
30 O 0
min O 0
of O 0
carotid O 0
occlusion O 0
( O 0
0 O 0
. O 0
298 O 0
mumol O 0
/ O 0
liter O 0
plasma O 0
; O 0
SD O 0
0 O 0
. O 0
078 O 0
) O 0
. O 0

Increased O 0
plasma O 0
malondialdehyde B-Chemical 0
was O 0
also O 0
recorded O 0
in O 0
two O 0
other O 0
groups O 0
of O 0
animals O 0
subjected O 0
to O 0
the O 0
same O 0
experimental O 0
model O 0
, O 0
one O 0
receiving O 0
20 O 0
mg O 0
/ O 0
kg O 0
b O 0
. O 0
w O 0
. O 0
of O 0
the O 0
cyclooxygenase O 0
inhibitor O 0
acetylsalicylate B-Chemical 0
intravenously O 0
immediately O 0
before O 0
ischemia B-Disease 0
, O 0
the O 0
other O 0
receiving O 0
650 O 0
micrograms O 0
/ O 0
kg O 0
b O 0
. O 0
w O 0
. O 0
of O 0
the O 0
hypotensive B-Disease 0
drug O 0
nitroprusside B-Chemical 0
at O 0
a O 0
flow O 0
rate O 0
of O 0
103 O 0
microliters O 0
/ O 0
min O 0
intravenously O 0
during O 0
ischemia B-Disease 0
, O 0
although O 0
in O 0
this O 0
latter O 0
group O 0
malondialdehyde B-Chemical 0
was O 0
significantly O 0
higher O 0
. O 0

The O 0
present O 0
data O 0
indicate O 0
that O 0
the O 0
determination O 0
of O 0
malondialdehyde B-Chemical 0
, O 0
oxypurines B-Chemical 0
, O 0
and O 0
nucleosides B-Chemical 0
in O 0
peripheral O 0
blood O 0
, O 0
may O 0
be O 0
used O 0
to O 0
monitor O 0
the O 0
metabolic O 0
alterations O 0
of O 0
tissues O 0
occurring O 0
during O 0
ischemic B-Disease 0
phenomena O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Acute O 0
renal B-Disease 0
toxicity I-Disease 0
of O 0
doxorubicin B-Chemical 0
( O 0
adriamycin B-Chemical 0
) O 0
- O 0
loaded O 0
cyanoacrylate B-Chemical 0
nanoparticles O 0
. O 0

Acute O 0
doxorubicin B-Chemical 0
- O 0
loaded O 0
nanoparticle O 0
( O 0
DXNP O 0
) O 0
renal B-Disease 0
toxicity I-Disease 0
was O 0
explored O 0
in O 0
both O 0
normal O 0
rats O 0
and O 0
rats O 0
with O 0
experimental O 0
glomerulonephritis B-Disease 0
. O 0

In O 0
normal O 0
rats O 0
, O 0
2 O 0
/ O 0
6 O 0
rats O 0
given O 0
free O 0
doxorubicin B-Chemical 0
( O 0
DX B-Chemical 0
) O 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
died O 0
within O 0
one O 0
week O 0
, O 0
whereas O 0
all O 0
control O 0
animals O 0
and O 0
all O 0
rats O 0
having O 0
received O 0
free O 0
NP O 0
or O 0
DXNP O 0
survived O 0
. O 0

A O 0
3 O 0
times O 0
higher O 0
proteinuria B-Disease 0
appeared O 0
in O 0
animals O 0
treated O 0
with O 0
DXNP O 0
than O 0
in O 0
those O 0
treated O 0
with O 0
DX B-Chemical 0
. O 0

Free O 0
NP O 0
did O 0
not O 0
provoke O 0
any O 0
proteinuria B-Disease 0
. O 0

Two O 0
hr O 0
post O 0
- O 0
injection O 0
, O 0
DXNP O 0
was O 0
2 O 0
. O 0
7 O 0
times O 0
more O 0
concentrated O 0
in O 0
kidneys O 0
than O 0
free O 0
DX B-Chemical 0
( O 0
p O 0
< O 0
0 O 0
. O 0
025 O 0
) O 0
. O 0

In O 0
rats O 0
with O 0
immune O 0
experimental O 0
glomerulonephritis B-Disease 0
, O 0
5 O 0
/ O 0
6 O 0
rats O 0
given O 0
DX B-Chemical 0
died O 0
within O 0
7 O 0
days O 0
, O 0
in O 0
contrast O 0
to O 0
animals O 0
treated O 0
by O 0
DXNP O 0
, O 0
NP O 0
, O 0
or O 0
untreated O 0
, O 0
which O 0
all O 0
survived O 0
. O 0

Proteinuria B-Disease 0
appeared O 0
in O 0
all O 0
series O 0
, O 0
but O 0
was O 0
2 O 0
- O 0
5 O 0
times O 0
more O 0
intense O 0
( O 0
p O 0
> O 0
0 O 0
. O 0
001 O 0
) O 0
and O 0
prolonged O 0
after O 0
doxorubicin B-Chemical 0
treatment O 0
( O 0
400 O 0
- O 0
700 O 0
mg O 0
/ O 0
day O 0
) O 0
, O 0
without O 0
significant O 0
difference O 0
between O 0
DXNP O 0
and O 0
DX B-Chemical 0
. O 0

Rats O 0
treated O 0
by O 0
unloaded O 0
NP O 0
behaved O 0
as O 0
controls O 0
. O 0

These O 0
results O 0
demonstrate O 0
that O 0
, O 0
in O 0
these O 0
experimental O 0
conditions O 0
, O 0
DXNP O 0
killed O 0
less O 0
animals O 0
than O 0
free O 0
DX B-Chemical 0
, O 0
despite O 0
of O 0
an O 0
enhanced O 0
renal B-Disease 0
toxicity I-Disease 0
of O 0
the O 0
former O 0
. O 0

Both O 0
effects O 0
( O 0
better O 0
survival O 0
and O 0
nephrosis B-Disease 0
) O 0
are O 0
most O 0
probably O 0
related O 0
to O 0
an O 0
enhanced O 0
capture O 0
of O 0
DXNP O 0
by O 0
cells O 0
of O 0
the O 0
mononuclear O 0
phagocyte O 0
system O 0
, O 0
including O 0
mesangial O 0
cells O 0
. O 0

Prostaglandin B-Chemical 0
E2 I-Chemical 0
- O 0
induced O 0
bladder B-Disease 0
hyperactivity I-Disease 0
in O 0
normal O 0
, O 0
conscious O 0
rats O 0
: O 0
involvement O 0
of O 0
tachykinins B-Chemical 0
? O 0

In O 0
normal O 0
conscious O 0
rats O 0
investigated O 0
by O 0
continuous O 0
cystometry O 0
, O 0
intravesically O 0
instilled O 0
prostaglandin B-Chemical 0
( I-Chemical 0
PG I-Chemical 0
) I-Chemical 0
E2 I-Chemical 0
facilitated O 0
micturition O 0
and O 0
increased O 0
basal O 0
intravesical O 0
pressure O 0
. O 0

The O 0
effect O 0
was O 0
attenuated O 0
by O 0
both O 0
the O 0
NK1 O 0
receptor O 0
selective O 0
antagonist O 0
RP B-Chemical 0
67 I-Chemical 0
, I-Chemical 0
580 I-Chemical 0
and O 0
the O 0
NK2 O 0
receptor O 0
selective O 0
antagonist O 0
SR B-Chemical 0
48 I-Chemical 0
, I-Chemical 0
968 I-Chemical 0
, O 0
given O 0
intra O 0
- O 0
arterially O 0
, O 0
suggesting O 0
that O 0
it O 0
was O 0
mediated O 0
by O 0
stimulation O 0
of O 0
both O 0
NK1 O 0
and O 0
NK2 O 0
receptors O 0
. O 0

Intra O 0
- O 0
arterially O 0
given O 0
PGE2 B-Chemical 0
produced O 0
a O 0
distinct O 0
increase O 0
in O 0
bladder O 0
pressure O 0
before O 0
initiating O 0
a O 0
micturition O 0
reflex O 0
, O 0
indicating O 0
that O 0
the O 0
PG B-Chemical 0
had O 0
a O 0
direct O 0
contractant O 0
effect O 0
on O 0
the O 0
detrusor O 0
smooth O 0
muscle O 0
. O 0

The O 0
effect O 0
of O 0
intra O 0
- O 0
arterial O 0
PGE2 B-Chemical 0
could O 0
not O 0
be O 0
blocked O 0
by O 0
intra O 0
- O 0
arterial O 0
RP B-Chemical 0
67 I-Chemical 0
, I-Chemical 0
580 I-Chemical 0
or O 0
SR B-Chemical 0
48 I-Chemical 0
, I-Chemical 0
968 I-Chemical 0
, O 0
which O 0
opens O 0
the O 0
possibility O 0
that O 0
the O 0
micturition O 0
reflex O 0
elicited O 0
by O 0
intra O 0
- O 0
arterial O 0
PGE2 B-Chemical 0
was O 0
mediated O 0
by O 0
pathways O 0
other O 0
than O 0
the O 0
reflex O 0
initiated O 0
when O 0
the O 0
PG B-Chemical 0
was O 0
given O 0
intravesically O 0
. O 0

The O 0
present O 0
results O 0
thus O 0
suggest O 0
that O 0
intra O 0
- O 0
arterial O 0
PGE2 B-Chemical 0
, O 0
given O 0
near O 0
the O 0
bladder O 0
, O 0
may O 0
initiate O 0
micturition O 0
in O 0
the O 0
normal O 0
rat O 0
chiefly O 0
by O 0
directly O 0
contracting O 0
the O 0
smooth O 0
muscle O 0
of O 0
the O 0
detrusor O 0
. O 0

However O 0
, O 0
when O 0
given O 0
intravesically O 0
, O 0
PGE2 B-Chemical 0
may O 0
stimulate O 0
micturition O 0
by O 0
releasing O 0
tachykinins B-Chemical 0
from O 0
nerves O 0
in O 0
and O 0
/ O 0
or O 0
immediately O 0
below O 0
the O 0
urothelium O 0
. O 0

These O 0
tachykinins B-Chemical 0
, O 0
in O 0
turn O 0
, O 0
initiate O 0
a O 0
micturition O 0
reflex O 0
by O 0
stimulating O 0
NK1 O 0
and O 0
NK2 O 0
receptors O 0
. O 0

Prostanoids B-Chemical 0
may O 0
, O 0
via O 0
release O 0
of O 0
tachykinins B-Chemical 0
, O 0
contribute O 0
to O 0
both O 0
urge O 0
and O 0
bladder B-Disease 0
hyperactivity I-Disease 0
seen O 0
in O 0
inflammatory O 0
conditions O 0
of O 0
the O 0
lower O 0
urinary O 0
tract O 0
. O 0

Refractory O 0
cardiogenic B-Disease 0
shock I-Disease 0
and O 0
complete O 0
heart B-Disease 0
block I-Disease 0
after O 0
verapamil B-Chemical 0
SR O 0
and O 0
metoprolol B-Chemical 0
treatment O 0
. O 0

A O 0
case O 0
report O 0
. O 0

A O 0
seventy O 0
- O 0
eight O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
presented O 0
with O 0
complete O 0
heart B-Disease 0
block I-Disease 0
and O 0
refractory O 0
hypotension B-Disease 0
two O 0
days O 0
after O 0
a O 0
therapeutic O 0
dose O 0
of O 0
sustained O 0
- O 0
release O 0
verapamil B-Chemical 0
with O 0
concomitant O 0
use O 0
of O 0
metoprolol B-Chemical 0
. O 0

The O 0
patient O 0
continued O 0
to O 0
remain O 0
hypotensive B-Disease 0
with O 0
complete O 0
heart B-Disease 0
block I-Disease 0
, O 0
even O 0
with O 0
multiple O 0
uses O 0
of O 0
intravenous O 0
atropine B-Chemical 0
as O 0
well O 0
as O 0
high O 0
doses O 0
of O 0
pressor O 0
agents O 0
such O 0
as O 0
dopamine B-Chemical 0
and O 0
dobutamine B-Chemical 0
. O 0

However O 0
, O 0
shortly O 0
after O 0
the O 0
use O 0
of O 0
intravenous O 0
calcium B-Chemical 0
chloride I-Chemical 0
, O 0
the O 0
refractory O 0
hypotension B-Disease 0
and O 0
complete O 0
heart B-Disease 0
block I-Disease 0
resolved O 0
. O 0

Protective O 0
effect O 0
of O 0
misoprostol B-Chemical 0
on O 0
indomethacin B-Chemical 0
induced O 0
renal B-Disease 0
dysfunction I-Disease 0
in O 0
elderly O 0
patients O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
evaluate O 0
the O 0
possible O 0
protective O 0
effects O 0
of O 0
misoprostol B-Chemical 0
on O 0
renal O 0
function O 0
in O 0
hospitalized O 0
elderly O 0
patients O 0
treated O 0
with O 0
indomethacin B-Chemical 0
. O 0

METHODS O 0
: O 0
Forty O 0
- O 0
five O 0
hospitalized O 0
elderly O 0
patients O 0
( O 0
> O 0
65 O 0
years O 0
old O 0
) O 0
who O 0
required O 0
therapy O 0
with O 0
nonsteroidal O 0
antiinflammatory O 0
drugs O 0
( O 0
NSAID O 0
) O 0
were O 0
randomly O 0
assigned O 0
to O 0
receive O 0
either O 0
indomethacin B-Chemical 0
, O 0
150 O 0
mg O 0
/ O 0
day O 0
( O 0
Group O 0
A O 0
) O 0
, O 0
or O 0
indomethacin B-Chemical 0
150 O 0
mg O 0
/ O 0
day O 0
plus O 0
misoprostol B-Chemical 0
at O 0
0 O 0
. O 0
6 O 0
mg O 0
/ O 0
day O 0
( O 0
Group O 0
B O 0
) O 0
. O 0

Laboratory O 0
variables O 0
of O 0
renal O 0
function O 0
[ O 0
serum O 0
creatinine B-Chemical 0
, 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
electrolytes O 0
] O 0
were O 0
evaluated O 0
before O 0
initiation O 0
of O 0
therapy O 0
and O 0
every O 0
2 O 0
days O 0
, O 0
until O 0
termination O 0
of O 0
the O 0
study O 0
( O 0
a O 0
period O 0
of O 0
at O 0
least O 0
6 O 0
days O 0
) O 0
. O 0

Response O 0
to O 0
treatment O 0
was O 0
estimated O 0
by O 0
the O 0
visual O 0
analog O 0
scale O 0
for O 0
severity O 0
of O 0
pain B-Disease 0
. O 0

RESULTS O 0
: O 0
Forty O 0
- O 0
two O 0
patients O 0
completed O 0
the O 0
study O 0
, O 0
22 O 0
in O 0
Group O 0
A O 0
and O 0
20 O 0
in O 0
Group O 0
B O 0
. O 0

BUN B-Chemical 0
and O 0
creatinine B-Chemical 0
increased O 0
by O 0
> O 0
50 O 0
% O 0
of O 0
baseline O 0
levels O 0
in O 0
54 O 0
and O 0
45 O 0
% O 0
of O 0
Group O 0
A O 0
patients O 0
, O 0
respectively O 0
, O 0
compared O 0
to O 0
only O 0
20 O 0
and O 0
10 O 0
% O 0
of O 0
Group O 0
B O 0
patients O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Potassium B-Chemical 0
( O 0
K B-Chemical 0
) O 0
increment O 0
of O 0
0 O 0
. O 0
6 O 0
mEq O 0
/ O 0
l O 0
or O 0
more O 0
was O 0
observed O 0
in O 0
50 O 0
% O 0
of O 0
Group O 0
A O 0
, O 0
but O 0
in O 0
only O 0
15 O 0
% O 0
of O 0
Group O 0
B O 0
patients O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

The O 0
mean O 0
increments O 0
in O 0
BUN B-Chemical 0
, O 0
creatinine B-Chemical 0
, O 0
and O 0
K B-Chemical 0
were O 0
reduced O 0
by O 0
63 O 0
, O 0
80 O 0
, O 0
and O 0
42 O 0
% O 0
, O 0
respectively O 0
, O 0
in O 0
Group O 0
B O 0
patients O 0
compared O 0
to O 0
Group O 0
A O 0
. O 0
Response O 0
to O 0
treatment O 0
did O 0
not O 0
differ O 0
significantly O 0
between O 0
the O 0
2 O 0
groups O 0
. O 0

CONCLUSION O 0
: O 0
Hospitalized O 0
elderly O 0
patients O 0
are O 0
at O 0
risk O 0
for O 0
developing O 0
indomethacin B-Chemical 0
related O 0
renal B-Disease 0
dysfunction I-Disease 0
. O 0

Addition O 0
of O 0
misoprostol B-Chemical 0
can O 0
minimize O 0
this O 0
renal B-Disease 0
impairment I-Disease 0
without O 0
affecting O 0
pain B-Disease 0
control O 0
. O 0

Cognitive B-Disease 0
deterioration I-Disease 0
from O 0
long O 0
- O 0
term O 0
abuse O 0
of O 0
dextromethorphan B-Chemical 0
: O 0
a O 0
case O 0
report O 0
. O 0

Dextromethorphan B-Chemical 0
( O 0
DM B-Chemical 0
) O 0
, O 0
the O 0
dextrorotatory O 0
isomer O 0
of O 0
3 B-Chemical 0
- I-Chemical 0
hydroxy I-Chemical 0
- I-Chemical 0
N I-Chemical 0
- I-Chemical 0
methylmorphinan I-Chemical 0
, O 0
is O 0
the O 0
main O 0
ingredient O 0
in O 0
a O 0
number O 0
of O 0
widely O 0
available O 0
, O 0
over O 0
- O 0
the O 0
- O 0
counter O 0
antitussives O 0
. O 0

Initial O 0
studies O 0
( O 0
Bornstein O 0
1968 O 0
) O 0
showed O 0
that O 0
it O 0
possessed O 0
no O 0
respiratory O 0
suppressant O 0
effects O 0
and O 0
no O 0
addiction O 0
liability O 0
. O 0

Subsequently O 0
, O 0
however O 0
, O 0
several O 0
articles O 0
reporting O 0
abuse O 0
of O 0
this O 0
drug O 0
have O 0
appeared O 0
in O 0
the O 0
literature O 0
. O 0

The O 0
drug O 0
is O 0
known O 0
to O 0
cause O 0
a O 0
variety O 0
of O 0
acute O 0
toxic O 0
effects O 0
, O 0
ranging O 0
from O 0
nausea B-Disease 0
, O 0
restlessness B-Disease 0
, O 0
insomnia B-Disease 0
, O 0
ataxia B-Disease 0
, O 0
slurred O 0
speech O 0
and O 0
nystagmus B-Disease 0
to O 0
mood O 0
changes O 0
, O 0
perceptual O 0
alterations O 0
, O 0
inattention O 0
, O 0
disorientation O 0
and O 0
aggressive B-Disease 0
behavior I-Disease 0
( O 0
Rammer O 0
et O 0
al O 0
1988 O 0
; O 0
Katona O 0
and O 0
Watson O 0
1986 O 0
; O 0
Isbell O 0
and O 0
Fraser O 0
1953 O 0
; O 0
Devlin O 0
et O 0
al O 0
1985 O 0
; O 0
McCarthy O 0
1971 O 0
; O 0
Dodds O 0
and O 0
Revai O 0
1967 O 0
; O 0
Degkwitz O 0
1964 O 0
; O 0
Hildebrand O 0
et O 0
al O 0
1989 O 0
) O 0
. O 0

There O 0
have O 0
also O 0
been O 0
two O 0
reported O 0
fatalities O 0
from O 0
DM B-Chemical 0
overdoses O 0
( O 0
Fleming O 0
1986 O 0
) O 0
. O 0

However O 0
, O 0
there O 0
are O 0
no O 0
reports O 0
describing O 0
the O 0
effects O 0
of O 0
chronic O 0
abuse O 0
. O 0

This O 0
report O 0
describes O 0
a O 0
case O 0
of O 0
cognitive B-Disease 0
deterioration I-Disease 0
resulting O 0
from O 0
prolonged O 0
use O 0
of O 0
DM B-Chemical 0
. O 0

Effects O 0
of O 0
ouabain B-Chemical 0
on O 0
myocardial O 0
oxygen B-Chemical 0
supply O 0
and O 0
demand O 0
in O 0
patients O 0
with O 0
chronic O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
. O 0

A O 0
hemodynamic O 0
, O 0
volumetric O 0
, O 0
and O 0
metabolic O 0
study O 0
in O 0
patients O 0
without O 0
heart B-Disease 0
failure I-Disease 0
. O 0

The O 0
effects O 0
of O 0
digitalis B-Chemical 0
glycosides I-Chemical 0
on O 0
myocardial O 0
oxygen B-Chemical 0
supply O 0
and O 0
demand O 0
are O 0
of O 0
particular O 0
interest O 0
in O 0
the O 0
presence O 0
of O 0
obstructive O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
, O 0
but O 0
have O 0
not O 0
been O 0
measured O 0
previously O 0
in O 0
man O 0
. O 0

We O 0
assessed O 0
the O 0
effects O 0
of O 0
ouabain B-Chemical 0
( O 0
0 O 0
. O 0
015 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
) O 0
on O 0
hemodynamic O 0
, O 0
volumetric O 0
, O 0
and O 0
metabolic O 0
parameters O 0
in O 0
11 O 0
patients O 0
with O 0
severe O 0
chronic O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
without O 0
clinical O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
. O 0

Because O 0
the O 0
protocol O 0
was O 0
long O 0
and O 0
involved O 0
interventions O 0
which O 0
might O 0
affect O 0
the O 0
determinations O 0
, O 0
we O 0
also O 0
studied O 0
in O 0
nine O 0
patients O 0
using O 0
an O 0
identical O 0
protocol O 0
except O 0
that O 0
ouabain B-Chemical 0
administration O 0
was O 0
omitted O 0
. O 0

Left O 0
ventricular O 0
end O 0
- O 0
diastolic O 0
pressure O 0
and O 0
left O 0
ventricular O 0
end O 0
- O 0
diastolic O 0
volume O 0
fell O 0
in O 0
each O 0
patient O 0
given O 0
ouabain B-Chemical 0
, O 0
even O 0
though O 0
they O 0
were O 0
initially O 0
elevated O 0
in O 0
only O 0
two O 0
patients O 0
. O 0

Left O 0
ventricular O 0
end O 0
- O 0
diastolic O 0
pressure O 0
fell O 0
from O 0
11 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
4 O 0
( O 0
mean O 0
+ O 0
/ O 0
- O 0
SE O 0
) O 0
to O 0
5 O 0
. O 0
6 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
9 O 0
mm O 0
Hg 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
left O 0
ventricular O 0
end O 0
- O 0
diastolic O 0
volume O 0
fell O 0
from O 0
100 O 0
+ O 0
/ O 0
- O 0
17 O 0
to O 0
82 O 0
+ O 0
/ O 0
- O 0
12 O 0
ml O 0
/ O 0
m2 O 0
( O 0
P O 0
less O 0
than O 0
0 O 0
. O 0
01 O 0
) O 0
1 O 0
h O 0
after O 0
ouabain B-Chemical 0
infusion O 0
was O 0
completed O 0
. O 0

The O 0
maximum O 0
velocity O 0
of O 0
contractile O 0
element O 0
shortening O 0
increased O 0
from O 0
1 O 0
. O 0
68 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
11 O 0
ml O 0
/ O 0
s O 0
to O 0
2 O 0
. O 0
18 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
21 O 0
muscle O 0
- O 0
lengths O 0
/ O 0
s O 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
is O 0
consistent O 0
with O 0
an O 0
increase O 0
in O 0
contractility O 0
. O 0

No O 0
significant O 0
change O 0
in O 0
these O 0
parameters O 0
occurred O 0
in O 0
the O 0
control O 0
patients O 0
. O 0

No O 0
significant O 0
change O 0
in O 0
myocardial O 0
oxygen B-Chemical 0
consumption O 0
occurred O 0
after O 0
ouabain B-Chemical 0
administration O 0
but O 0
this O 0
may O 0
be O 0
related O 0
to O 0
a O 0
greater O 0
decrease O 0
in O 0
mean O 0
arterial O 0
pressure O 0
in O 0
the O 0
ouabain B-Chemical 0
patients O 0
than O 0
in O 0
the O 0
control O 0
patients O 0
. O 0

We O 0
conclude O 0
that O 0
in O 0
patients O 0
with O 0
chronic O 0
coronary B-Disease 0
artery I-Disease 0
disease I-Disease 0
who O 0
are O 0
not O 0
in O 0
clinical O 0
congestive B-Disease 0
heart I-Disease 0
failure I-Disease 0
left B-Disease 0
ventricular I-Disease 0
end I-Disease 0
- I-Disease 0
diastolic I-Disease 0
volume I-Disease 0
falls I-Disease 0
after O 0
ouabain B-Chemical 0
administration O 0
even O 0
when O 0
it O 0
is O 0
initially O 0
normal O 0
. O 0

Though O 0
this O 0
fall O 0
would O 0
be O 0
associated O 0
with O 0
a O 0
decrease O 0
in O 0
wall O 0
tension O 0
, O 0
and O 0
, O 0
therefore O 0
, O 0
of O 0
myocardial O 0
oxygen B-Chemical 0
consumption O 0
, O 0
it O 0
may O 0
not O 0
be O 0
of O 0
sufficient O 0
magnitude O 0
to O 0
prevent O 0
a O 0
net O 0
increase O 0
in O 0
myocardial O 0
oxygen B-Chemical 0
consumption O 0
. O 0

Nevertheless O 0
, O 0
compensatory O 0
mechanisms O 0
prevent O 0
a O 0
deterioration O 0
of O 0
resting O 0
myocardial O 0
metabolism O 0
. O 0

Dexamethasone B-Chemical 0
- O 0
induced O 0
ocular B-Disease 0
hypertension I-Disease 0
in O 0
perfusion O 0
- O 0
cultured O 0
human O 0
eyes O 0
. O 0

PURPOSE O 0
: O 0
Glucocorticoid O 0
administration O 0
can O 0
lead O 0
to O 0
the O 0
development O 0
of O 0
ocular B-Disease 0
hypertension I-Disease 0
and O 0
corticosteroid B-Disease 0
glaucoma I-Disease 0
in O 0
a O 0
subset O 0
of O 0
the O 0
population O 0
through O 0
a O 0
decrease O 0
in O 0
the O 0
aqueous O 0
humor O 0
outflow O 0
facility 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
whether O 0
glucocorticoid O 0
treatment O 0
can O 0
directly O 0
affect O 0
the O 0
outflow O 0
facility O 0
of O 0
isolated O 0
, O 0
perfusion O 0
- O 0
cultured O 0
human O 0
eyes O 0
. O 0

METHODS O 0
: O 0
The O 0
anterior O 0
segments O 0
of O 0
human O 0
donor O 0
eyes O 0
from O 0
regional O 0
eye O 0
banks O 0
were O 0
placed O 0
in O 0
a O 0
constant O 0
flow O 0
, O 0
variable O 0
pressure O 0
perfusion O 0
culture O 0
system O 0
. O 0

Paired O 0
eyes O 0
were O 0
perfused O 0
in O 0
serum O 0
- O 0
free O 0
media O 0
with O 0
or O 0
without O 0
10 O 0
( O 0
- O 0
7 O 0
) O 0
M O 0
dexamethasone B-Chemical 0
for O 0
12 O 0
days O 0
. O 0

Intraocular O 0
pressure O 0
was O 0
monitored O 0
daily O 0
. O 0

After O 0
incubation O 0
, O 0
the O 0
eyes O 0
were O 0
morphologically O 0
characterized O 0
by O 0
light O 0
microscopy O 0
, O 0
transmission O 0
and O 0
scanning O 0
electron O 0
microscopy O 0
, O 0
and O 0
scanning O 0
laser O 0
confocal O 0
microscopy O 0
. O 0

RESULTS O 0
: O 0
A O 0
significant O 0
increase O 0
in O 0
intraocular O 0
pressure O 0
developed O 0
in O 0
13 O 0
of O 0
the O 0
44 O 0
pairs O 0
of O 0
eyes O 0
perfused O 0
with O 0
dexamethasone B-Chemical 0
with O 0
an O 0
average O 0
pressure O 0
rise O 0
of O 0
17 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
8 O 0
mm O 0
Hg O 0
after O 0
12 O 0
days O 0
of O 0
dexamethasone B-Chemical 0
exposure O 0
. O 0

The O 0
contralateral O 0
control O 0
eyes O 0
, O 0
which O 0
did O 0
not O 0
receive O 0
dexamethasone B-Chemical 0
, O 0
maintained O 0
a O 0
stable O 0
intraocular O 0
pressure O 0
during O 0
the O 0
same O 0
period O 0
. O 0

The O 0
outflow O 0
pathway O 0
of O 0
the O 0
untreated O 0
eyes O 0
appeared O 0
morphologically O 0
normal O 0
. O 0

In O 0
contrast O 0
, O 0
the O 0
dexamethasone B-Chemical 0
- O 0
treated O 0
hypertensive B-Disease 0
eyes I-Disease 0
had O 0
thickened O 0
trabecular O 0
beams O 0
, O 0
decreased O 0
intertrabecular O 0
spaces O 0
, O 0
thickened O 0
juxtacanalicular O 0
tissue O 0
, O 0
activated O 0
trabecular O 0
meshwork O 0
cells O 0
, O 0
and O 0
increased O 0
amounts O 0
of O 0
amorphogranular O 0
extracellular O 0
material O 0
, O 0
especially O 0
in O 0
the O 0
juxtacanalicular O 0
tissue O 0
and O 0
beneath O 0
the O 0
endothelial O 0
lining O 0
of O 0
the O 0
canal O 0
of O 0
Schlemm O 0
. O 0

The O 0
dexamethasone B-Chemical 0
- O 0
treated O 0
nonresponder O 0
eyes O 0
appeared O 0
to O 0
be O 0
morphologically O 0
similar O 0
to O 0
the O 0
untreated O 0
eyes O 0
, O 0
although O 0
several O 0
subtle O 0
dexamethasone B-Chemical 0
- O 0
induced O 0
morphologic O 0
changes O 0
were O 0
evident O 0
. O 0

CONCLUSION O 0
: O 0
Dexamethasone B-Chemical 0
treatment O 0
of O 0
isolated O 0
, O 0
perfusion O 0
- O 0
cultured O 0
human O 0
eyes O 0
led O 0
to O 0
the O 0
generation O 0
of O 0
ocular B-Disease 0
hypertension I-Disease 0
in O 0
approximately O 0
30 O 0
% O 0
of O 0
the O 0
dexamethasone B-Chemical 0
- O 0
treated O 0
eyes O 0
. O 0

Steroid B-Chemical 0
treatment O 0
resulted O 0
in O 0
morphologic O 0
changes O 0
in O 0
the O 0
trabecular O 0
meshwork O 0
similar O 0
to O 0
those O 0
reported O 0
for O 0
corticosteroid B-Disease 0
glaucoma I-Disease 0
and O 0
open B-Disease 0
angle I-Disease 0
glaucoma I-Disease 0
. O 0

This O 0
system O 0
may O 0
provide O 0
an O 0
acute O 0
model O 0
in O 0
which O 0
to O 0
study O 0
the O 0
pathogenic O 0
mechanisms O 0
involved O 0
in O 0
steroid B-Disease 0
glaucoma I-Disease 0
and O 0
primary B-Disease 0
open I-Disease 0
angle I-Disease 0
glaucoma I-Disease 0
. O 0

Auditory O 0
disturbance O 0
associated O 0
with O 0
interscalene O 0
brachial O 0
plexus O 0
block O 0
. O 0

We O 0
performed O 0
an O 0
audiometric O 0
study O 0
in O 0
20 O 0
patients O 0
who O 0
underwent O 0
surgery O 0
of O 0
the O 0
shoulder O 0
region O 0
under O 0
an O 0
interscalene O 0
brachial O 0
plexus O 0
block O 0
( O 0
IBPB O 0
) O 0
. O 0

Bupivacaine B-Chemical 0
0 O 0
. O 0
75 O 0
% O 0
with O 0
adrenaline B-Chemical 0
was O 0
given O 0
followed O 0
by O 0
a O 0
24 O 0
- O 0
hr O 0
continuous O 0
infusion O 0
of O 0
0 O 0
. O 0
25 O 0
% O 0
bupivacaine B-Chemical 0
. O 0

Three O 0
audiometric O 0
threshold O 0
measurements O 0
( O 0
0 O 0
. O 0
25 O 0
- O 0
18 O 0
kHz O 0
) O 0
were O 0
made O 0
: O 0
the O 0
first O 0
before O 0
IBPB O 0
, O 0
the O 0
second O 0
2 O 0
- O 0
6 O 0
h O 0
after O 0
surgery O 0
and O 0
the O 0
third O 0
on O 0
the O 0
first O 0
day O 0
after O 0
operation O 0
. O 0

In O 0
four O 0
patients O 0
hearing B-Disease 0
impairment I-Disease 0
on O 0
the O 0
side O 0
of O 0
the O 0
block O 0
was O 0
demonstrated O 0
after O 0
operation O 0
, O 0
in O 0
three O 0
measurements O 0
on O 0
the O 0
day O 0
of O 0
surgery O 0
and O 0
in O 0
one O 0
on O 0
the O 0
following O 0
day O 0
. O 0

The O 0
frequencies O 0
at O 0
which O 0
the O 0
impairment O 0
occurred O 0
varied O 0
between O 0
patients O 0
; O 0
in O 0
one O 0
only O 0
low O 0
frequencies O 0
( O 0
0 O 0
. O 0
25 O 0
- O 0
0 O 0
. O 0
5 O 0
kHz O 0
) O 0
were O 0
involved O 0
. O 0

The O 0
maximum O 0
change O 0
in O 0
threshold O 0
was O 0
35 O 0
dB O 0
at O 0
6 O 0
kHz O 0
measured O 0
at O 0
the O 0
end O 0
of O 0
the O 0
continuous O 0
infusion O 0
of O 0
bupivacaine B-Chemical 0
. O 0

This O 0
patient O 0
had O 0
hearing O 0
threshold O 0
changes O 0
( O 0
15 O 0
- O 0
20 O 0
dB O 0
) O 0
at O 0
6 O 0
- O 0
10 O 0
kHz O 0
on O 0
the O 0
opposite O 0
side O 0
also O 0
. O 0

IBPB O 0
may O 0
cause O 0
transient O 0
auditory B-Disease 0
dysfunction I-Disease 0
in O 0
the O 0
ipsilateral O 0
ear O 0
, O 0
possibly O 0
via O 0
an O 0
effect O 0
on O 0
sympathetic O 0
innervation O 0
. O 0

The O 0
safety O 0
and O 0
efficacy O 0
of O 0
combination O 0
N B-Chemical 0
- I-Chemical 0
butyl I-Chemical 0
- I-Chemical 0
deoxynojirimycin I-Chemical 0
( O 0
SC B-Chemical 0
- I-Chemical 0
48334 I-Chemical 0
) O 0
and O 0
zidovudine B-Chemical 0
in O 0
patients O 0
with O 0
HIV B-Disease 0
- I-Disease 0
1 I-Disease 0
infection I-Disease 0
and O 0
200 O 0
- O 0
500 O 0
CD4 O 0
cells O 0
/ O 0
mm3 O 0
. O 0

We O 0
conducted O 0
a O 0
double O 0
- O 0
blind O 0
, O 0
randomized O 0
phase O 0
II O 0
study O 0
to O 0
evaluate O 0
the O 0
safety O 0
and O 0
activity O 0
of O 0
combination O 0
therapy O 0
with O 0
N B-Chemical 0
- I-Chemical 0
butyl I-Chemical 0
- I-Chemical 0
deoxynojirimycin I-Chemical 0
( O 0
SC B-Chemical 0
- I-Chemical 0
48334 I-Chemical 0
) O 0
( O 0
an O 0
alpha O 0
- O 0
glucosidase O 0
I O 0
inhibitor O 0
) O 0
and O 0
zidovudine B-Chemical 0
versus O 0
zidovudine B-Chemical 0
alone O 0
. O 0

Patients O 0
with O 0
200 O 0
to O 0
500 O 0
CD4 O 0
cells O 0
/ O 0
mm3 O 0
who O 0
tolerated O 0
< O 0
or O 0
= O 0
12 O 0
weeks O 0
of O 0
prior O 0
zidovudine B-Chemical 0
therapy O 0
received O 0
SC B-Chemical 0
- I-Chemical 0
48334 I-Chemical 0
( O 0
1000 O 0
mg O 0
every O 0
8 O 0
h O 0
) O 0
and O 0
zidovudine B-Chemical 0
( O 0
100 O 0
mg O 0
every O 0
8 O 0
h O 0
) O 0
or O 0
zidovudine B-Chemical 0
and O 0
placebo O 0
. O 0

Sixty O 0
patients O 0
received O 0
combination O 0
therapy O 0
and O 0
58 O 0
, O 0
zidovudine B-Chemical 0
and O 0
placebo O 0
. O 0

Twenty O 0
- O 0
three O 0
patients O 0
( O 0
38 O 0
% O 0
) O 0
and O 0
15 O 0
( O 0
26 O 0
% O 0
) O 0
, O 0
in O 0
the O 0
combination O 0
and O 0
zidovudine B-Chemical 0
groups O 0
, O 0
respectively O 0
, O 0
discontinued O 0
therapy O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
15 O 0
) O 0
. O 0

The O 0
mean O 0
SC B-Chemical 0
- I-Chemical 0
48334 I-Chemical 0
steady O 0
- O 0
state O 0
trough O 0
level O 0
( O 0
4 O 0
. O 0
04 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
99 O 0
micrograms O 0
/ O 0
ml O 0
) O 0
was O 0
below O 0
the O 0
in O 0
vitro O 0
inhibitory O 0
concentration O 0
for O 0
human O 0
immunodeficiency B-Disease 0
virus O 0
( O 0
HIV O 0
) O 0
. O 0

The O 0
mean O 0
increase O 0
in O 0
CD4 O 0
cells O 0
at O 0
week O 0
4 O 0
was O 0
73 O 0
. O 0
8 O 0
cells O 0
/ O 0
mm3 O 0
and O 0
52 O 0
. O 0
4 O 0
cells O 0
/ O 0
mm3 O 0
for O 0
the O 0
combination O 0
and O 0
zidovudine B-Chemical 0
groups O 0
, O 0
respectively O 0
( O 0
p O 0
> O 0
0 O 0
. O 0
36 O 0
) O 0
. O 0

For O 0
patients O 0
with O 0
prior O 0
zidovudine B-Chemical 0
therapy O 0
, O 0
the O 0
mean O 0
change O 0
in O 0
CD4 O 0
cells O 0
in O 0
the O 0
combination O 0
and O 0
zidovudine B-Chemical 0
groups O 0
was O 0
63 O 0
. O 0
7 O 0
cells O 0
/ O 0
mm3 O 0
and O 0
4 O 0
. O 0
9 O 0
cells O 0
/ O 0
mm3 O 0
at O 0
week O 0
8 O 0
and O 0
6 O 0
. O 0
8 O 0
cells O 0
/ O 0
mm3 O 0
and O 0
- O 0
45 O 0
. O 0
1 O 0
cells O 0
/ O 0
mm3 O 0
at O 0
week O 0
16 O 0
, O 0
respectively O 0
. O 0

The O 0
number O 0
of O 0
patients O 0
with O 0
suppression O 0
of O 0
HIV O 0
p24 O 0
antigenemia O 0
in O 0
the O 0
combination O 0
and O 0
zidovudine B-Chemical 0
groups O 0
was O 0
six O 0
( O 0
40 O 0
% O 0
) O 0
and O 0
two O 0
( O 0
11 O 0
% O 0
) O 0
at O 0
week O 0
4 O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
10 O 0
) O 0
and O 0
five O 0
( O 0
45 O 0
% O 0
) O 0
and O 0
two O 0
( O 0
14 O 0
% O 0
) O 0
at O 0
week O 0
24 O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
08 O 0
) O 0
, O 0
respectively O 0
. O 0

Diarrhea B-Disease 0
, O 0
flatulence B-Disease 0
, O 0
abdominal B-Disease 0
pain I-Disease 0
, O 0
and O 0
weight B-Disease 0
loss I-Disease 0
were O 0
common O 0
for O 0
combination O 0
recipients O 0
. O 0
( O 0
ABSTRACT O 0
TRUNCATED O 0
AT O 0
250 O 0
WORDS O 0
) O 0

Prolonged O 0
paralysis B-Disease 0
due O 0
to O 0
nondepolarizing B-Chemical 0
neuromuscular I-Chemical 0
blocking I-Chemical 0
agents I-Chemical 0
and O 0
corticosteroids B-Chemical 0
. O 0

The O 0
long O 0
- O 0
term O 0
use O 0
of O 0
nondepolarizing B-Chemical 0
neuromuscular I-Chemical 0
blocking I-Chemical 0
agents I-Chemical 0
( O 0
ND B-Chemical 0
- I-Chemical 0
NMBA I-Chemical 0
) O 0
has O 0
recently O 0
been O 0
implicated O 0
as O 0
a O 0
cause O 0
of O 0
prolonged O 0
muscle B-Disease 0
weakness I-Disease 0
, O 0
although O 0
the O 0
site O 0
of O 0
the O 0
lesion O 0
and O 0
the O 0
predisposing O 0
factors O 0
have O 0
been O 0
unclear O 0
. O 0

We O 0
report O 0
3 O 0
patients O 0
( O 0
age O 0
37 O 0
- O 0
52 O 0
years O 0
) O 0
with O 0
acute O 0
respiratory B-Disease 0
insufficiency I-Disease 0
who O 0
developed O 0
prolonged O 0
weakness B-Disease 0
following O 0
the O 0
discontinuation O 0
of O 0
ND B-Chemical 0
- I-Chemical 0
NMBAs I-Chemical 0
. O 0

Two O 0
patients O 0
also O 0
received O 0
intravenous O 0
corticosteroids B-Chemical 0
. O 0

Renal O 0
function O 0
was O 0
normal O 0
but O 0
hepatic O 0
function O 0
was O 0
impaired O 0
in O 0
all O 0
patients O 0
, O 0
and O 0
all O 0
had O 0
acidosis B-Disease 0
. O 0

Electrophysiologic O 0
studies O 0
revealed O 0
low O 0
amplitude O 0
compound O 0
motor O 0
action O 0
potentials O 0
, O 0
normal O 0
sensory O 0
studies O 0
, O 0
and O 0
fibrillations O 0
. O 0

Repetitive O 0
stimulation O 0
at O 0
2 O 0
Hz O 0
showed O 0
a O 0
decremental O 0
response O 0
in O 0
2 O 0
patients O 0
. O 0

The O 0
serum O 0
vecuronium B-Chemical 0
level O 0
measured O 0
in O 0
1 O 0
patient O 0
14 O 0
days O 0
after O 0
the O 0
drug O 0
had O 0
been O 0
discontinued O 0
was O 0
172 O 0
ng O 0
/ O 0
mL O 0
. O 0

A O 0
muscle O 0
biopsy O 0
in O 0
this O 0
patient O 0
showed O 0
loss B-Disease 0
of I-Disease 0
thick I-Disease 0
, I-Disease 0
myosin I-Disease 0
filaments I-Disease 0
. O 0

The O 0
weakness B-Disease 0
in O 0
these O 0
patients O 0
is O 0
due O 0
to O 0
pathology B-Disease 0
at I-Disease 0
both I-Disease 0
the I-Disease 0
neuromuscular I-Disease 0
junction I-Disease 0
( O 0
most O 0
likely O 0
due O 0
to O 0
ND B-Chemical 0
- I-Chemical 0
NMBA I-Chemical 0
) O 0
and O 0
muscle O 0
( O 0
most O 0
likely O 0
due O 0
to O 0
corticosteroids B-Chemical 0
) O 0
. O 0

Hepatic B-Disease 0
dysfunction I-Disease 0
and O 0
acidosis B-Disease 0
are O 0
contributing O 0
risk O 0
factors O 0
. O 0

Failure O 0
of O 0
ancrod O 0
in O 0
the O 0
treatment O 0
of O 0
heparin B-Chemical 0
- O 0
induced O 0
arterial O 0
thrombosis B-Disease 0
. O 0

The O 0
morbidity O 0
and O 0
mortality O 0
associated O 0
with O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombosis B-Disease 0
remain O 0
high O 0
despite O 0
numerous O 0
empirical O 0
therapies O 0
. O 0

Ancrod O 0
has O 0
been O 0
used O 0
successfully O 0
for O 0
prophylaxis O 0
against O 0
development O 0
of O 0
thrombosis B-Disease 0
in O 0
patients O 0
with O 0
heparin B-Chemical 0
induced O 0
platelet B-Disease 0
aggregation I-Disease 0
who O 0
require O 0
brief O 0
reexposure O 0
to O 0
heparin B-Chemical 0
, O 0
but O 0
its O 0
success O 0
in O 0
patients O 0
who O 0
have O 0
developed O 0
the O 0
thrombosis B-Disease 0
syndrome O 0
is O 0
not O 0
well O 0
defined O 0
. O 0

The O 0
authors O 0
present O 0
a O 0
case O 0
of O 0
failure O 0
of O 0
ancrod O 0
treatment O 0
in O 0
a O 0
patient O 0
with O 0
heparin B-Chemical 0
- O 0
induced O 0
thrombosis B-Disease 0
. O 0

Water B-Disease 0
intoxication I-Disease 0
associated O 0
with O 0
oxytocin B-Chemical 0
administration O 0
during O 0
saline O 0
- O 0
induced O 0
abortion B-Disease 0
. O 0

Four O 0
cases O 0
of O 0
water B-Disease 0
intoxication I-Disease 0
in O 0
connection O 0
with O 0
oxytocin B-Chemical 0
administration O 0
during O 0
saline O 0
- O 0
induced O 0
abortions B-Disease 0
are O 0
described O 0
. O 0

The O 0
mechanism O 0
of O 0
water B-Disease 0
intoxication I-Disease 0
is O 0
discussed O 0
in O 0
regard O 0
to O 0
these O 0
cases O 0
. O 0

Oxytocin B-Chemical 0
administration O 0
during O 0
midtrimester O 0
- O 0
induced O 0
abortions B-Disease 0
is O 0
advocated O 0
only O 0
if O 0
it O 0
can O 0
be O 0
carried O 0
out O 0
under O 0
careful O 0
observations O 0
of O 0
an O 0
alert O 0
nursing O 0
staff O 0
, O 0
aware O 0
of O 0
the O 0
symptoms O 0
of O 0
water B-Disease 0
intoxication I-Disease 0
and O 0
instructed O 0
to O 0
watch O 0
the O 0
diuresis O 0
and O 0
report O 0
such O 0
early O 0
signs O 0
of O 0
the O 0
syndrome O 0
as O 0
asthenia B-Disease 0
, O 0
muscular O 0
irritability B-Disease 0
, O 0
or O 0
headaches B-Disease 0
. O 0

The O 0
oxytocin B-Chemical 0
should O 0
be O 0
given O 0
only O 0
in O 0
Ringers O 0
lactate B-Chemical 0
or O 0
, O 0
alternately O 0
, O 0
in O 0
Ringers O 0
lactate B-Chemical 0
and O 0
a O 0
5 O 0
per O 0
cent O 0
dextrose B-Chemical 0
and O 0
water O 0
solutions O 0
. O 0

The O 0
urinary O 0
output O 0
should O 0
be O 0
monitored O 0
and O 0
the O 0
oxytocin B-Chemical 0
administration O 0
discontinued O 0
and O 0
the O 0
serum O 0
electrolytes O 0
checked O 0
if O 0
the O 0
urinary O 0
output O 0
decreases O 0
. O 0

The O 0
oxytocin B-Chemical 0
should O 0
not O 0
be O 0
administered O 0
in O 0
excess O 0
of O 0
36 O 0
hours O 0
. O 0

If O 0
the O 0
patient O 0
has O 0
not O 0
aborted O 0
by O 0
then O 0
the O 0
oxytocin B-Chemical 0
should O 0
be O 0
discontinued O 0
for O 0
10 O 0
to O 0
12 O 0
hours O 0
in O 0
order O 0
to O 0
perform O 0
electrolyte O 0
determinations O 0
and O 0
correct O 0
any O 0
electrolyte O 0
imbalance O 0
. O 0

Light O 0
chain O 0
proteinuria B-Disease 0
and O 0
cellular O 0
mediated O 0
immunity O 0
in O 0
rifampin B-Chemical 0
treated O 0
patients O 0
with O 0
tuberculosis B-Disease 0
. O 0

Light O 0
chain O 0
proteinuria B-Disease 0
was O 0
found O 0
in O 0
9 O 0
of O 0
17 O 0
tuberculosis B-Disease 0
patients O 0
treated O 0
with O 0
rifampin B-Chemical 0
. O 0

Concomitant O 0
assay O 0
of O 0
cellular O 0
mediated O 0
immunity O 0
in O 0
these O 0
patients O 0
using O 0
skin O 0
test O 0
antigen O 0
and O 0
a O 0
lymphokine O 0
in O 0
vitro O 0
test O 0
provided O 0
results O 0
that O 0
were O 0
different O 0
. O 0

Response O 0
to O 0
Varidase O 0
skin O 0
test O 0
antigen O 0
was O 0
negative O 0
for O 0
all O 0
eight O 0
tuberculosis B-Disease 0
patients O 0
tested O 0
, O 0
but O 0
there O 0
occurred O 0
a O 0
hyper O 0
- O 0
responsiveness O 0
of O 0
the O 0
lymphocytes O 0
of O 0
these O 0
eight O 0
patients O 0
to O 0
phytomitogen O 0
( O 0
PHA O 0
- O 0
P O 0
) O 0
. O 0
as O 0
well O 0
as O 0
of O 0
those O 0
of O 0
seven O 0
other O 0
tuberculous B-Disease 0
patients O 0
. O 0

This O 0
last O 0
finding O 0
may O 0
be O 0
related O 0
to O 0
time O 0
of O 0
testing O 0
and O 0
/ O 0
or O 0
endogenous O 0
serum O 0
binding O 0
of O 0
rifampin B-Chemical 0
which O 0
could O 0
have O 0
inhibited O 0
mitogen O 0
activity O 0
for O 0
the O 0
lymphocyte O 0
. O 0

KF17837 B-Chemical 0
: O 0
a O 0
novel O 0
selective O 0
adenosine B-Chemical 0
A2A O 0
receptor O 0
antagonist O 0
with O 0
anticataleptic O 0
activity O 0
. O 0

KF17837 B-Chemical 0
is O 0
a O 0
novel O 0
selective O 0
adenosine B-Chemical 0
A2A O 0
receptor O 0
antagonist O 0
. O 0

Oral O 0
administration O 0
of O 0
KF17837 B-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
, O 0
10 O 0
. O 0
0 O 0
and O 0
30 O 0
. O 0
0 O 0
mg O 0
/ O 0
kg O 0
) O 0
significantly O 0
ameliorated O 0
the O 0
cataleptic B-Disease 0
responses O 0
induced O 0
by O 0
intracerebroventricular O 0
administration O 0
of O 0
an O 0
adenosine B-Chemical 0
A2A O 0
receptor O 0
agonist O 0
, O 0
CGS B-Chemical 0
21680 I-Chemical 0
( O 0
10 O 0
micrograms O 0
) O 0
, O 0
in O 0
a O 0
dose O 0
- O 0
dependent O 0
manner O 0
. O 0

KF17837 B-Chemical 0
also O 0
reduced O 0
the O 0
catalepsy B-Disease 0
induced O 0
by 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
and O 0
by O 0
reserpine B-Chemical 0
( O 0
5 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

These O 0
anticataleptic O 0
effects O 0
were O 0
exhibited O 0
dose O 0
dependently O 0
at O 0
doses O 0
from O 0
0 O 0
. O 0
625 O 0
and O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
p O 0
. O 0
o O 0
. O 0
, O 0
respectively O 0
. O 0

Moreover O 0
, O 0
KF17837 B-Chemical 0
( O 0
0 O 0
. O 0
625 O 0
mg O 0
/ O 0
kg O 0
p O 0
. O 0
o O 0
. O 0
) O 0
potentiated O 0
the O 0
anticataleptic O 0
effects O 0
of O 0
a O 0
subthreshold O 0
dose O 0
of O 0
L B-Chemical 0
- I-Chemical 0
3 I-Chemical 0
, I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
dihydroxyphenylalanine I-Chemical 0
( O 0
L B-Chemical 0
- I-Chemical 0
DOPA I-Chemical 0
; O 0
25 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
plus O 0
benserazide B-Chemical 0
( O 0
6 O 0
. O 0
25 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

These O 0
results O 0
suggested O 0
that O 0
KF17837 B-Chemical 0
is O 0
a O 0
centrally O 0
active O 0
adenosine B-Chemical 0
A2A O 0
receptor O 0
antagonist O 0
and O 0
that O 0
the O 0
dopaminergic O 0
function O 0
of O 0
the O 0
nigrostriatal O 0
pathway O 0
is O 0
potentiated O 0
by O 0
adenosine B-Chemical 0
A2A O 0
receptor O 0
antagonists O 0
. O 0

Furthermore O 0
, O 0
KF17837 B-Chemical 0
may O 0
be O 0
a O 0
useful O 0
drug O 0
in O 0
the O 0
treatment O 0
of O 0
parkinsonism B-Disease 0
. O 0

Effect O 0
of O 0
nondopaminergic O 0
drugs O 0
on O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
in O 0
MPTP B-Chemical 0
- O 0
treated O 0
monkeys O 0
. O 0

A O 0
group O 0
of O 0
four O 0
monkeys O 0
was O 0
rendered O 0
parkinsonian B-Disease 0
with O 0
the O 0
toxin O 0
MPTP B-Chemical 0
. O 0

They O 0
were O 0
then O 0
treated O 0
chronically O 0
with O 0
L B-Chemical 0
- I-Chemical 0
DOPA I-Chemical 0
/ I-Chemical 0
benserazide I-Chemical 0
50 O 0
/ O 0
12 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
given O 0
orally O 0
daily O 0
for O 0
2 O 0
months O 0
. O 0

This O 0
dose O 0
produced O 0
a O 0
striking O 0
antiparkinsonian O 0
effect O 0
, O 0
but O 0
all O 0
animals O 0
manifested O 0
dyskinesia B-Disease 0
. O 0

A O 0
series O 0
of O 0
agents O 0
acting O 0
primarily O 0
on O 0
neurotransmitters O 0
other O 0
than O 0
dopamine B-Chemical 0
were O 0
then O 0
tested O 0
in O 0
combination O 0
with O 0
L B-Chemical 0
- I-Chemical 0
DOPA I-Chemical 0
to O 0
see O 0
if O 0
the O 0
dyskinetic B-Disease 0
movements O 0
would O 0
be O 0
modified O 0
. O 0

Several O 0
drugs O 0
, O 0
including O 0
clonidine B-Chemical 0
, O 0
physostigmine B-Chemical 0
, O 0
methysergide B-Chemical 0
, O 0
5 B-Chemical 0
- I-Chemical 0
MDOT I-Chemical 0
, O 0
propranolol B-Chemical 0
, O 0
and O 0
MK B-Chemical 0
- I-Chemical 0
801 I-Chemical 0
, O 0
markedly O 0
reduced O 0
the O 0
dyskinetic B-Disease 0
movements O 0
but O 0
at O 0
the O 0
cost O 0
of O 0
a O 0
return O 0
of O 0
parkinsonian B-Disease 0
symptomatology O 0
. O 0

However O 0
, O 0
yohimbine B-Chemical 0
and O 0
meperidine B-Chemical 0
reduced O 0
predominantly O 0
the O 0
dyskinetic B-Disease 0
movements O 0
. O 0

Baclofen B-Chemical 0
was O 0
also O 0
useful O 0
in O 0
one O 0
monkey O 0
against O 0
a O 0
more O 0
dystonic B-Disease 0
form O 0
of O 0
dyskinesia B-Disease 0
. O 0

Atropine B-Chemical 0
converted O 0
the O 0
dystonic B-Disease 0
movements O 0
into O 0
chorea B-Disease 0
. O 0

Hallucinations B-Disease 0
and O 0
ifosfamide B-Chemical 0
- O 0
induced O 0
neurotoxicity B-Disease 0
. O 0

BACKGROUND O 0
: O 0
Hallucinations B-Disease 0
as O 0
a O 0
symptom O 0
of O 0
central O 0
neurotoxicity B-Disease 0
are O 0
a O 0
known O 0
but O 0
poorly O 0
described O 0
side O 0
effect O 0
of O 0
ifosfamide B-Chemical 0
. O 0

Most O 0
cases O 0
of O 0
ifosfamide B-Chemical 0
- O 0
induced O 0
hallucinations B-Disease 0
have O 0
been O 0
reported O 0
with O 0
other O 0
mental O 0
status O 0
changes O 0
. O 0

METHODS O 0
: O 0
The O 0
authors O 0
interviewed O 0
six O 0
persons O 0
with O 0
ifosfamide B-Chemical 0
- O 0
induced O 0
hallucinations B-Disease 0
in O 0
the O 0
presence O 0
of O 0
a O 0
clear O 0
sensorium O 0
. O 0

All O 0
patients O 0
were O 0
receiving O 0
high O 0
- O 0
dose O 0
ifosfamide B-Chemical 0
as O 0
part O 0
of O 0
their O 0
bone O 0
marrow O 0
transplant O 0
procedure O 0
. O 0

RESULTS O 0
: O 0
Hallucinations B-Disease 0
occurred O 0
only O 0
when O 0
the O 0
patient O 0
' O 0
s O 0
eyes O 0
were O 0
closed O 0
and O 0
, O 0
in O 0
all O 0
but O 0
one O 0
case O 0
, O 0
were O 0
reported O 0
as O 0
disturbing O 0
or O 0
frightening O 0
. O 0

Underreporting O 0
of O 0
these O 0
hallucinations B-Disease 0
by O 0
patients O 0
is O 0
likely O 0
. O 0

CONCLUSIONS O 0
: O 0
Hallucinations B-Disease 0
may O 0
be O 0
the O 0
sole O 0
or O 0
first O 0
manifestation O 0
of O 0
neurotoxicity B-Disease 0
. O 0

The O 0
incidence O 0
may O 0
be O 0
dose O 0
and O 0
infusion O 0
- O 0
time O 0
related O 0
. O 0

The O 0
clinician O 0
should O 0
be O 0
alerted O 0
for O 0
possible O 0
ifosfamide B-Chemical 0
- O 0
induced O 0
hallucinations B-Disease 0
, O 0
which O 0
may O 0
occur O 0
without O 0
other O 0
signs O 0
of O 0
neurotoxicity B-Disease 0
. O 0

" O 0
Eyes O 0
- O 0
closed O 0
" O 0
hallucinatory B-Disease 0
experiences O 0
appear O 0
to O 0
be O 0
an O 0
unusual O 0
feature O 0
of O 0
this O 0
presentation O 0
. O 0

Patients O 0
anxious O 0
about O 0
this O 0
experience O 0
respond O 0
well O 0
to O 0
support O 0
and O 0
education O 0
about O 0
this O 0
occurrence O 0
. O 0

Optimal O 0
pharmacologic O 0
management O 0
of O 0
disturbed O 0
patients O 0
is O 0
unclear O 0
. O 0

If O 0
agitation B-Disease 0
becomes O 0
marked O 0
, O 0
high O 0
- O 0
potency O 0
neuroleptics O 0
( O 0
i O 0
. O 0
e O 0
. O 0
, O 0
haloperidol B-Chemical 0
) O 0
may O 0
be O 0
effective O 0
. O 0

Photodistributed O 0
nifedipine B-Chemical 0
- O 0
induced O 0
facial O 0
telangiectasia B-Disease 0
. O 0

Five O 0
months O 0
after O 0
starting O 0
nifedipine B-Chemical 0
( O 0
Adalat B-Chemical 0
) O 0
, O 0
two O 0
patients O 0
developed O 0
photodistributed O 0
facial O 0
telangiectasia B-Disease 0
, O 0
which O 0
became O 0
more O 0
noticeable O 0
with O 0
time O 0
. O 0

Neither O 0
patient O 0
complained O 0
of O 0
photosensitivity O 0
or O 0
flushing B-Disease 0
. O 0

Both O 0
patients O 0
reported O 0
a O 0
significant O 0
cosmetic O 0
improvement O 0
after O 0
discontinuing O 0
the O 0
drug O 0
. O 0

One O 0
commenced O 0
the O 0
closely O 0
related O 0
drug O 0
amlodipine B-Chemical 0
3 O 0
years O 0
later O 0
, O 0
with O 0
recurrence O 0
of O 0
telangiectasia B-Disease 0
. O 0

The O 0
photodistribution O 0
of O 0
the O 0
telangiectasia B-Disease 0
suggests O 0
a O 0
significant O 0
drug O 0
/ O 0
light O 0
interaction O 0
. O 0

Penicillamine B-Chemical 0
- O 0
induced O 0
rapidly O 0
progressive O 0
glomerulonephritis B-Disease 0
in O 0
a O 0
patient O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
. O 0

A O 0
67 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
presented O 0
rapidly O 0
progressive O 0
glomerulonephritis B-Disease 0
( O 0
RPGN B-Disease 0
) O 0
after O 0
5 O 0
months O 0
of O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
( O 0
250 O 0
mg O 0
/ O 0
day O 0
) O 0
treatment O 0
. O 0

Light O 0
microscopy O 0
study O 0
showed O 0
severe O 0
glomerulonephritis B-Disease 0
with O 0
crescent O 0
formation O 0
in O 0
60 O 0
% O 0
of O 0
the O 0
glomeruli O 0
and O 0
infiltration O 0
of O 0
inflammatory O 0
cells O 0
in O 0
the O 0
wall O 0
of O 0
an O 0
arteriole O 0
. O 0

Immunofluorescence O 0
revealed O 0
scanty O 0
granular O 0
IgG O 0
, O 0
IgA O 0
and O 0
C3 O 0
deposits O 0
along O 0
the O 0
capillary O 0
walls O 0
and O 0
mesangium O 0
. O 0

The O 0
patient O 0
was O 0
treated O 0
with O 0
steroid B-Chemical 0
pulse O 0
, O 0
plasmapheresis O 0
, O 0
cyclophosphamide B-Chemical 0
and O 0
antiplatelet B-Chemical 0
agents I-Chemical 0
. O 0

A O 0
complete O 0
recovery O 0
of O 0
renal O 0
function O 0
was O 0
achieved O 0
in O 0
a O 0
few O 0
weeks O 0
. O 0

This O 0
new O 0
case O 0
of O 0
RPGN B-Disease 0
in O 0
the O 0
course O 0
of O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
treatment O 0
emphasizes O 0
the O 0
need O 0
for O 0
frequent O 0
monitoring O 0
of O 0
renal O 0
function O 0
and O 0
evaluation O 0
of O 0
urinary O 0
sediment O 0
and O 0
proteinuria B-Disease 0
in O 0
these O 0
patients O 0
. O 0

The O 0
prompt O 0
discontinuation O 0
of O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
and O 0
vigorous O 0
treatment O 0
measures O 0
could O 0
allow O 0
for O 0
a O 0
good O 0
prognosis O 0
as O 0
in O 0
this O 0
case O 0
. O 0

A O 0
case O 0
of O 0
polymyositis B-Disease 0
in O 0
a O 0
patient O 0
with O 0
primary B-Disease 0
biliary I-Disease 0
cirrhosis I-Disease 0
treated O 0
with O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
. O 0

Although O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
has O 0
been O 0
used O 0
for O 0
many O 0
rheumatologic B-Disease 0
diseases I-Disease 0
, O 0
toxicity B-Disease 0
limits O 0
its O 0
usefulness O 0
in O 0
many O 0
patients O 0
. O 0

Polymyositis B-Disease 0
/ O 0
dermatomyositis B-Disease 0
can O 0
develop O 0
as O 0
one O 0
of O 0
the O 0
autoimmune O 0
complications O 0
of O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
treatment O 0
, O 0
but O 0
its O 0
exact O 0
pathogenesis O 0
remains O 0
unclear O 0
. O 0

We O 0
report O 0
a O 0
patient O 0
with O 0
primary B-Disease 0
biliary I-Disease 0
cirrhosis I-Disease 0
, O 0
who O 0
developed O 0
polymyositis B-Disease 0
while O 0
receiving O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
therapy O 0
. O 0

We O 0
described O 0
the O 0
special O 0
clinical O 0
course O 0
of O 0
the O 0
patient O 0
. O 0

Patients O 0
receiving O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
therapy O 0
should O 0
be O 0
followed O 0
carefully O 0
for O 0
the O 0
development O 0
of O 0
autoimmune O 0
complications O 0
like O 0
polymyositis B-Disease 0
/ O 0
dermatomyositis B-Disease 0
. O 0

Hyperalgesia B-Disease 0
and O 0
myoclonus B-Disease 0
in O 0
terminal O 0
cancer B-Disease 0
patients O 0
treated O 0
with O 0
continuous O 0
intravenous O 0
morphine B-Chemical 0
. O 0

Eight O 0
cancer B-Disease 0
patients O 0
in O 0
the O 0
terminal O 0
stages O 0
of O 0
the O 0
disease O 0
treated O 0
with O 0
high O 0
doses O 0
of O 0
intravenous O 0
morphine B-Chemical 0
developed O 0
hyperalgesia B-Disease 0
. O 0

All O 0
cases O 0
were O 0
retrospectively O 0
sampled O 0
from O 0
three O 0
different O 0
hospitals O 0
in O 0
Copenhagen O 0
. O 0

Five O 0
patients O 0
developed O 0
universal O 0
hyperalgesia B-Disease 0
and O 0
hyperesthesia B-Disease 0
which O 0
in O 0
2 O 0
cases O 0
were O 0
accompanied O 0
by O 0
myoclonus B-Disease 0
. O 0

In O 0
3 O 0
patients O 0
a O 0
pre O 0
- O 0
existing O 0
neuralgia B-Disease 0
increased O 0
to O 0
excruciating O 0
intensity O 0
and O 0
in O 0
2 O 0
of O 0
these O 0
cases O 0
myoclonus B-Disease 0
occurred O 0
simultaneously O 0
. O 0

Although O 0
only O 0
few O 0
clinical O 0
descriptions O 0
of O 0
the O 0
relationship O 0
between O 0
hyperalgesia B-Disease 0
/ O 0
myoclonus B-Disease 0
and O 0
high O 0
doses O 0
of O 0
morphine B-Chemical 0
are O 0
available O 0
, O 0
experimental O 0
support O 0
from O 0
animal O 0
studies O 0
indicates O 0
that O 0
morphine B-Chemical 0
, O 0
or O 0
its O 0
metabolites O 0
, O 0
plays O 0
a O 0
causative O 0
role O 0
for O 0
the O 0
observed O 0
behavioural O 0
syndrome O 0
. O 0

The O 0
possible O 0
mechanisms O 0
are O 0
discussed O 0
and O 0
treatment O 0
proposals O 0
given O 0
suggesting O 0
the O 0
use O 0
of O 0
more O 0
efficacious O 0
opioids O 0
with O 0
less O 0
excitatory O 0
potency O 0
in O 0
these O 0
situations O 0
. O 0

Liposomal O 0
daunorubicin B-Chemical 0
in O 0
advanced O 0
Kaposi B-Disease 0
' I-Disease 0
s I-Disease 0
sarcoma I-Disease 0
: O 0
a O 0
phase O 0
II O 0
study O 0
. O 0

We O 0
report O 0
a O 0
non O 0
- O 0
randomized O 0
Phase O 0
II O 0
clinical O 0
trial O 0
to O 0
assess O 0
the O 0
efficacy O 0
and O 0
safety O 0
of O 0
liposomal O 0
daunorubicin B-Chemical 0
( O 0
DaunoXome O 0
) O 0
in O 0
the O 0
treatment O 0
of O 0
AIDS B-Disease 0
related O 0
Kaposi B-Disease 0
' I-Disease 0
s I-Disease 0
sarcoma I-Disease 0
. O 0

Eleven O 0
homosexual O 0
men O 0
with O 0
advanced O 0
Kaposi B-Disease 0
' I-Disease 0
s I-Disease 0
sarcoma I-Disease 0
were O 0
entered O 0
in O 0
the O 0
trial O 0
. O 0

Changes O 0
in O 0
size O 0
, O 0
colour O 0
and O 0
associated O 0
oedema B-Disease 0
of O 0
selected O 0
' O 0
target O 0
' O 0
lesions O 0
were O 0
measured O 0
. O 0

Clinical O 0
, O 0
biochemical O 0
and O 0
haematological O 0
toxicities B-Disease 0
were O 0
assessed O 0
. O 0

Ten O 0
subjects O 0
were O 0
evaluated O 0
. O 0

A O 0
partial O 0
response O 0
was O 0
achieved O 0
in O 0
four O 0
, O 0
of O 0
whom O 0
two O 0
subsequently O 0
relapsed O 0
. O 0

Stabilization O 0
of O 0
Kaposi B-Disease 0
' I-Disease 0
s I-Disease 0
sarcoma I-Disease 0
occurred O 0
in O 0
the O 0
remaining O 0
six O 0
, O 0
maintained O 0
until O 0
the O 0
end O 0
of O 0
the O 0
trial O 0
period O 0
in O 0
four O 0
. O 0

The O 0
drug O 0
was O 0
generally O 0
well O 0
tolerated O 0
, O 0
with O 0
few O 0
mild O 0
symptoms O 0
of O 0
toxicity B-Disease 0
. O 0

The O 0
main O 0
problem O 0
encountered O 0
was O 0
haematological O 0
toxicity B-Disease 0
, O 0
with O 0
three O 0
subjects O 0
experiencing O 0
severe O 0
neutropenia B-Disease 0
( O 0
neutrophil O 0
count O 0
< O 0
0 O 0
. O 0
5 O 0
x O 0
10 O 0
( O 0
9 O 0
) O 0
/ O 0
l O 0
) O 0
. O 0

There O 0
was O 0
no O 0
evidence O 0
of O 0
cardiotoxicity B-Disease 0
. O 0

In O 0
this O 0
small O 0
patient O 0
sample O 0
, O 0
liposomal O 0
daunorubicin B-Chemical 0
was O 0
an O 0
effective O 0
and O 0
well O 0
tolerated O 0
agent O 0
in O 0
the O 0
treatment O 0
of O 0
Kaposi B-Disease 0
' I-Disease 0
s I-Disease 0
sarcoma I-Disease 0
. O 0

Long O 0
- O 0
term O 0
effects O 0
of O 0
vincristine B-Chemical 0
on O 0
the O 0
peripheral O 0
nervous O 0
system O 0
. O 0

Forty O 0
patients O 0
with O 0
Non B-Disease 0
- I-Disease 0
Hodgkin I-Disease 0
' I-Disease 0
s I-Disease 0
Lymphoma I-Disease 0
treated O 0
with O 0
vincristine B-Chemical 0
between O 0
1984 O 0
and O 0
1990 O 0
( O 0
cumulative O 0
dose O 0
12 O 0
mg O 0
in O 0
18 O 0
- O 0
24 O 0
weeks O 0
) O 0
were O 0
investigated O 0
in O 0
order O 0
to O 0
evaluate O 0
the O 0
long O 0
term O 0
effects O 0
of O 0
vincristine B-Chemical 0
on O 0
the O 0
peripheral O 0
nervous O 0
system O 0
. O 0

The O 0
patients O 0
were O 0
interviewed O 0
with O 0
emphasis O 0
on O 0
neuropathic B-Disease 0
symptoms I-Disease 0
. O 0

Physical O 0
and O 0
quantitative O 0
sensory O 0
examination O 0
with O 0
determination O 0
of O 0
vibratory O 0
perception O 0
and O 0
thermal O 0
discrimination O 0
thresholds O 0
were O 0
performed O 0
, O 0
four O 0
to O 0
77 O 0
months O 0
( O 0
median O 0
34 O 0
months O 0
) O 0
after O 0
vincristine B-Chemical 0
treatment O 0
. O 0

Twenty O 0
- O 0
seven O 0
patients O 0
reported O 0
neuropathic B-Disease 0
symptoms I-Disease 0
. O 0

In O 0
13 O 0
of O 0
these O 0
27 O 0
patients O 0
symptoms O 0
were O 0
still O 0
present O 0
at O 0
the O 0
time O 0
of O 0
examination O 0
. O 0

In O 0
these O 0
patients O 0
sensory O 0
signs O 0
and O 0
symptoms O 0
predominated O 0
. O 0

In O 0
the O 0
other O 0
14 O 0
patients O 0
symptoms O 0
had O 0
been O 0
present O 0
in O 0
the O 0
past O 0
. O 0

Symptoms O 0
persisted O 0
maximally O 0
40 O 0
months O 0
since O 0
cessation O 0
of O 0
therapy O 0
. O 0

There O 0
was O 0
no O 0
age O 0
difference O 0
between O 0
patients O 0
with O 0
and O 0
without O 0
complaints O 0
at O 0
the O 0
time O 0
of O 0
examination O 0
. O 0

Normal O 0
reflexes O 0
were O 0
found O 0
in O 0
two O 0
third O 0
of O 0
patients O 0
. O 0

Neuropathic O 0
complaints O 0
were O 0
not O 0
very O 0
troublesome O 0
on O 0
the O 0
long O 0
term O 0
. O 0

It O 0
is O 0
concluded O 0
that O 0
with O 0
the O 0
above O 0
mentioned O 0
vincristine B-Chemical 0
dose O 0
schedule O 0
signs O 0
and O 0
symptoms O 0
of O 0
vincristine B-Chemical 0
neuropathy B-Disease 0
are O 0
reversible O 0
for O 0
a O 0
great O 0
deal O 0
and O 0
prognosis O 0
is O 0
fairly O 0
good O 0
. O 0

Hepatic O 0
adenomas B-Disease 0
and O 0
focal B-Disease 0
nodular I-Disease 0
hyperplasia I-Disease 0
of O 0
the O 0
liver O 0
in O 0
young O 0
women O 0
on O 0
oral B-Chemical 0
contraceptives I-Chemical 0
: O 0
case O 0
reports O 0
. O 0

Two O 0
cases O 0
of O 0
hepatic O 0
adenoma B-Disease 0
and O 0
one O 0
of O 0
focal B-Disease 0
nodular I-Disease 0
hyperplasia I-Disease 0
presumably O 0
associated O 0
with O 0
the O 0
use O 0
of O 0
oral B-Chemical 0
contraceptives I-Chemical 0
, O 0
are O 0
reported O 0
. O 0

Special O 0
reference O 0
is O 0
made O 0
to O 0
their O 0
clinical O 0
presentation O 0
, O 0
which O 0
may O 0
be O 0
totally O 0
asymptomatic O 0
. O 0

Liver O 0
- O 0
function O 0
tests O 0
are O 0
of O 0
little O 0
diagnostic O 0
value O 0
, O 0
but O 0
valuable O 0
information O 0
may O 0
be O 0
obtained O 0
from O 0
both O 0
liver O 0
scanning O 0
and O 0
hepatic O 0
angiography O 0
. O 0

Histologic O 0
differences O 0
and O 0
clinical O 0
similarities O 0
between O 0
hepatic O 0
adenoma B-Disease 0
and O 0
focal B-Disease 0
nodular I-Disease 0
hyperplasia I-Disease 0
of O 0
the O 0
liver O 0
are O 0
discussed O 0
. O 0

Loss O 0
of O 0
glutamate B-Chemical 0
decarboxylase O 0
mRNA O 0
- O 0
containing O 0
neurons O 0
in O 0
the O 0
rat O 0
dentate O 0
gyrus O 0
following O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
. O 0

In O 0
situ O 0
hybridization O 0
methods O 0
were O 0
used O 0
to O 0
determine O 0
if O 0
glutamic B-Chemical 0
acid I-Chemical 0
decarboxylase O 0
( O 0
GAD O 0
) O 0
mRNA O 0
- O 0
containing O 0
neurons O 0
within O 0
the O 0
hilus O 0
of O 0
the O 0
dentate O 0
gyrus O 0
are O 0
vulnerable O 0
to O 0
seizure B-Disease 0
- O 0
induced O 0
damage O 0
in O 0
a O 0
model O 0
of O 0
chronic O 0
seizures B-Disease 0
. O 0

Sprague O 0
- O 0
Dawley O 0
rats O 0
were O 0
injected O 0
intraperitoneally O 0
with O 0
pilocarpine B-Chemical 0
, O 0
and O 0
the O 0
hippocampal O 0
formation O 0
was O 0
studied O 0
histologically O 0
at O 0
1 O 0
, O 0
2 O 0
, O 0
4 O 0
, O 0
and O 0
8 O 0
week O 0
intervals O 0
after O 0
pilocarpine B-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
. O 0

In O 0
situ O 0
hybridization O 0
histochemistry O 0
, O 0
using O 0
a O 0
digoxigenin B-Chemical 0
- O 0
labeled O 0
GAD O 0
cRNA O 0
probe O 0
, O 0
demonstrated O 0
a O 0
substantial O 0
decrease O 0
in O 0
the O 0
number O 0
of O 0
GAD O 0
mRNA O 0
- O 0
containing O 0
neurons O 0
in O 0
the O 0
hilus O 0
of O 0
the O 0
dentate O 0
gyrus O 0
in O 0
the O 0
pilocarpine B-Chemical 0
- O 0
treated O 0
rats O 0
as O 0
compared O 0
to O 0
controls O 0
at O 0
all O 0
time O 0
intervals O 0
. O 0

Additional O 0
neuronanatomical O 0
studies O 0
, O 0
including O 0
cresyl B-Chemical 0
violet I-Chemical 0
staining O 0
, O 0
neuronal B-Disease 0
degeneration I-Disease 0
methods O 0
, O 0
and O 0
histochemical O 0
localization O 0
of O 0
glial O 0
fibrillary O 0
acidic O 0
protein O 0
, O 0
suggested O 0
that O 0
the O 0
decrease O 0
in O 0
the O 0
number O 0
of O 0
GAD O 0
mRNA O 0
- O 0
containing O 0
neurons O 0
was O 0
related O 0
to O 0
neuronal B-Disease 0
loss I-Disease 0
rather O 0
than O 0
to O 0
a O 0
decrease O 0
in O 0
GAD O 0
mRNA O 0
levels O 0
. O 0

The O 0
loss O 0
of O 0
GAD O 0
mRNA O 0
- O 0
containing O 0
neurons O 0
in O 0
the O 0
hilus O 0
contrasted O 0
with O 0
the O 0
relative O 0
preservation O 0
of O 0
labeled O 0
putative O 0
basket O 0
cells O 0
along O 0
the O 0
inner O 0
margin O 0
of O 0
the O 0
granule O 0
cell O 0
layer O 0
. O 0

Quantitative O 0
analyses O 0
of O 0
labeled O 0
neurons O 0
in O 0
three O 0
regions O 0
of O 0
the O 0
dentate O 0
gyrus O 0
in O 0
the O 0
1 O 0
and O 0
2 O 0
week O 0
groups O 0
showed O 0
statistically O 0
significant O 0
decreases O 0
in O 0
the O 0
mean O 0
number O 0
of O 0
GAD O 0
mRNA O 0
- O 0
containing O 0
neurons O 0
in O 0
the O 0
hilus O 0
of O 0
both O 0
groups O 0
of O 0
experimental O 0
animals O 0
. O 0

No O 0
significant O 0
differences O 0
were O 0
found O 0
in O 0
the O 0
molecular O 0
layer O 0
or O 0
the O 0
granule O 0
cell O 0
layer O 0
, O 0
which O 0
included O 0
labeled O 0
neurons O 0
along O 0
the O 0
lower O 0
margin O 0
of O 0
the O 0
granule O 0
cell O 0
layer O 0
. O 0

The O 0
results O 0
indicate O 0
that O 0
, O 0
in O 0
this O 0
model O 0
, O 0
a O 0
subpopulation O 0
of O 0
GAD O 0
mRNA O 0
- O 0
containing O 0
neurons O 0
within O 0
the O 0
dentate O 0
gyrus O 0
is O 0
selectively O 0
vulnerable O 0
to O 0
seizure B-Disease 0
- O 0
induced O 0
damage O 0
. O 0

Such O 0
differential O 0
vulnerability O 0
appears O 0
to O 0
be O 0
another O 0
indication O 0
of O 0
the O 0
heterogeneity O 0
of O 0
GABA B-Chemical 0
neurons O 0
. O 0

Effects O 0
of O 0
deliberate O 0
hypotension B-Disease 0
induced O 0
by O 0
labetalol B-Chemical 0
with O 0
isoflurane B-Chemical 0
on O 0
neuropsychological O 0
function O 0
. O 0

The O 0
effect O 0
of O 0
deliberate O 0
hypotension B-Disease 0
on O 0
brain O 0
function O 0
measured O 0
by O 0
neuropsychological O 0
tests O 0
was O 0
studied O 0
in O 0
41 O 0
adult O 0
patients O 0
. O 0

Twenty O 0
- O 0
four O 0
patients O 0
were O 0
anaesthetized O 0
for O 0
middle O 0
- O 0
ear O 0
surgery O 0
with O 0
deliberate O 0
hypotension B-Disease 0
induced O 0
by O 0
labetalol B-Chemical 0
with O 0
isoflurane B-Chemical 0
( O 0
hypotensive B-Disease 0
group O 0
) O 0
. O 0

Seventeen O 0
patients O 0
without O 0
hypotension B-Disease 0
served O 0
as O 0
a O 0
control O 0
group O 0
. O 0

The O 0
mean O 0
arterial O 0
pressure O 0
was O 0
77 O 0
+ O 0
/ O 0
- O 0
2 O 0
mmHg O 0
( O 0
10 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
3 O 0
kPa O 0
) O 0
before O 0
hypotension B-Disease 0
and O 0
50 O 0
+ O 0
/ O 0
- O 0
0 O 0
mmHg O 0
( O 0
6 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
0 O 0
kPa O 0
) O 0
during O 0
hypotension B-Disease 0
in O 0
the O 0
hypotensive B-Disease 0
group O 0
, O 0
and O 0
86 O 0
+ O 0
/ O 0
- O 0
2 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
3 O 0
kPa O 0
) O 0
during O 0
anaesthesia O 0
in O 0
the O 0
control O 0
group O 0
. O 0

The O 0
following O 0
psychological O 0
tests O 0
were O 0
performed O 0
: O 0
four O 0
subtests O 0
of O 0
the O 0
Wechsler O 0
Adult O 0
Intelligence O 0
Scale O 0
( O 0
similarities O 0
, O 0
digit O 0
span O 0
, O 0
vocabulary O 0
and O 0
digit O 0
symbol O 0
) O 0
, O 0
Trail O 0
- O 0
Making O 0
tests O 0
A O 0
and O 0
B O 0
, O 0
Zung O 0
tests O 0
( O 0
self O 0
- O 0
rating O 0
anxiety B-Disease 0
scale O 0
and O 0
self O 0
- O 0
rating O 0
depression B-Disease 0
scale O 0
) O 0
and O 0
two O 0
- O 0
part O 0
memory O 0
test O 0
battery O 0
with O 0
immediate O 0
and O 0
delayed O 0
recall O 0
. O 0

The O 0
tests O 0
were O 0
performed O 0
preoperatively O 0
and O 0
2 O 0
days O 0
postoperatively O 0
. O 0

There O 0
were O 0
no O 0
statistically O 0
significant O 0
differences O 0
between O 0
the O 0
groups O 0
in O 0
any O 0
of O 0
the O 0
tests O 0
in O 0
the O 0
changes O 0
from O 0
preoperative O 0
value O 0
to O 0
postoperative O 0
value O 0
. O 0

The O 0
results O 0
indicate O 0
that O 0
hypotension B-Disease 0
induced O 0
by O 0
labetalol B-Chemical 0
with O 0
isoflurane B-Chemical 0
has O 0
no O 0
significant O 0
harmful O 0
effects O 0
on O 0
mental O 0
functions O 0
compared O 0
to O 0
normotensive O 0
anaesthesia O 0
. O 0

Apparent O 0
cure O 0
of O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
by O 0
bone O 0
marrow O 0
transplantation O 0
. O 0

We O 0
describe O 0
the O 0
induction O 0
of O 0
sustained O 0
remissions O 0
and O 0
possible O 0
cure O 0
of O 0
severe O 0
erosive O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
( O 0
RA B-Disease 0
) O 0
by O 0
bone O 0
marrow O 0
transplantation O 0
( O 0
BMT O 0
) O 0
in O 0
2 O 0
patients O 0
. O 0

BMT O 0
was O 0
used O 0
to O 0
treat O 0
severe O 0
aplastic B-Disease 0
anemia I-Disease 0
which O 0
was O 0
caused O 0
by O 0
gold B-Chemical 0
in O 0
one O 0
case O 0
and O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
in O 0
the O 0
other O 0
. O 0

In O 0
the O 0
8 O 0
and O 0
6 O 0
years O 0
since O 0
the O 0
transplants O 0
( O 0
representing O 0
8 O 0
and O 0
4 O 0
years O 0
since O 0
cessation O 0
of O 0
all O 0
immunosuppressive O 0
therapy O 0
, O 0
respectively O 0
) O 0
, O 0
the O 0
RA B-Disease 0
in O 0
each O 0
case O 0
has O 0
been O 0
completely O 0
quiescent O 0
. O 0

Although O 0
short O 0
term O 0
remission O 0
of O 0
severe O 0
RA B-Disease 0
following O 0
BMT O 0
has O 0
been O 0
reported O 0
, O 0
these O 0
are O 0
the O 0
first O 0
cases O 0
for O 0
which O 0
prolonged O 0
followup O 0
has O 0
been O 0
available O 0
. O 0

This O 0
experience O 0
raises O 0
the O 0
question O 0
of O 0
the O 0
role O 0
of O 0
BMT O 0
itself O 0
as O 0
a O 0
therapeutic O 0
option O 0
for O 0
patients O 0
with O 0
uncontrolled O 0
destructive O 0
synovitis B-Disease 0
. O 0

Seizures B-Disease 0
induced O 0
by O 0
combined O 0
levomepromazine B-Chemical 0
- O 0
fluvoxamine B-Chemical 0
treatment O 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
combined O 0
levomepromazine B-Chemical 0
- O 0
fluvoxamine B-Chemical 0
treatment O 0
- O 0
induced O 0
seizures B-Disease 0
. O 0

It O 0
seems O 0
that O 0
combined O 0
treatment O 0
of O 0
fluvoxamine B-Chemical 0
with O 0
phenothiazines B-Chemical 0
may O 0
possess O 0
proconvulsive O 0
activity O 0
. O 0

Case O 0
report O 0
: O 0
pentamidine B-Chemical 0
and O 0
polymorphic O 0
ventricular B-Disease 0
tachycardia I-Disease 0
revisited O 0
. O 0

Pentamidine B-Chemical 0
isethionate I-Chemical 0
has O 0
been O 0
associated O 0
with O 0
ventricular B-Disease 0
tachyarrhythmias I-Disease 0
, O 0
including O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
. O 0

This O 0
article O 0
reports O 0
two O 0
cases O 0
of O 0
this O 0
complication O 0
and O 0
reviews O 0
all O 0
reported O 0
cases O 0
to O 0
date O 0
. O 0

Pentamidine B-Chemical 0
- O 0
induced O 0
torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
may O 0
be O 0
related O 0
to O 0
serum O 0
magnesium B-Chemical 0
levels O 0
and O 0
hypomagnesemia B-Disease 0
may O 0
synergistically O 0
induce O 0
torsade O 0
. O 0

Torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
occurred O 0
after O 0
an O 0
average O 0
of O 0
10 O 0
days O 0
of O 0
treatment O 0
with O 0
pentamidine B-Chemical 0
. O 0

In O 0
these O 0
patients O 0
, O 0
no O 0
other O 0
acute O 0
side O 0
effects O 0
of O 0
pentamidine B-Chemical 0
were O 0
observed O 0
. O 0

Torsade B-Disease 0
de I-Disease 0
pointes I-Disease 0
can O 0
be O 0
treated O 0
when O 0
recognized O 0
early O 0
, O 0
possibly O 0
without O 0
discontinuation O 0
of O 0
pentamidine B-Chemical 0
. O 0

When O 0
QTc B-Disease 0
interval I-Disease 0
prolongation I-Disease 0
is O 0
observed O 0
, O 0
early O 0
magnesium B-Chemical 0
supplementation O 0
is O 0
advocated O 0
. O 0

Efficacy O 0
and O 0
tolerability O 0
of O 0
lovastatin B-Chemical 0
in O 0
3390 O 0
women O 0
with O 0
moderate O 0
hypercholesterolemia B-Disease 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
evaluate O 0
the O 0
efficacy O 0
and O 0
safety O 0
of O 0
lovastatin B-Chemical 0
in O 0
women O 0
with O 0
moderate O 0
hypercholesterolemia B-Disease 0
. O 0

DESIGN O 0
: O 0
The O 0
Expanded O 0
Clinical O 0
Evaluation O 0
of O 0
Lovastatin B-Chemical 0
( O 0
EXCEL O 0
) O 0
Study O 0
, O 0
a O 0
multicenter O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
diet O 0
- O 0
and O 0
placebo O 0
- O 0
controlled O 0
trial O 0
, O 0
in O 0
which O 0
participants O 0
were O 0
randomly O 0
assigned O 0
to O 0
receive O 0
placebo O 0
or O 0
lovastatin B-Chemical 0
at O 0
doses O 0
of O 0
20 O 0
or O 0
40 O 0
mg O 0
once O 0
daily O 0
, O 0
or O 0
20 O 0
or O 0
40 O 0
mg O 0
twice O 0
daily O 0
for O 0
48 O 0
weeks O 0
. O 0

SETTING O 0
: O 0
Ambulatory O 0
patients O 0
recruited O 0
by O 0
362 O 0
participating O 0
centers O 0
throughout O 0
the O 0
United O 0
States O 0
. O 0

PATIENTS O 0
: O 0
Women O 0
( O 0
n O 0
= O 0
3390 O 0
) O 0
from O 0
the O 0
total O 0
cohort O 0
of O 0
8245 O 0
volunteers O 0
. O 0

MEASUREMENTS O 0
: O 0
Plasma O 0
total O 0
, O 0
low O 0
- O 0
density O 0
lipoprotein O 0
( O 0
LDL O 0
) O 0
, O 0
and O 0
high O 0
- O 0
density O 0
lipoprotein O 0
( O 0
HDL O 0
) O 0
cholesterol B-Chemical 0
, O 0
and O 0
triglycerides B-Chemical 0
; O 0
and O 0
laboratory O 0
and O 0
clinical O 0
evidence O 0
of O 0
adverse O 0
events O 0
monitored O 0
periodically O 0
throughout O 0
the O 0
study O 0
. O 0

RESULTS O 0
: O 0
Among O 0
women O 0
, O 0
lovastatin B-Chemical 0
( O 0
20 O 0
to O 0
80 O 0
mg O 0
/ O 0
d O 0
) O 0
produced O 0
sustained O 0
( O 0
12 O 0
- O 0
to O 0
48 O 0
- O 0
week O 0
) O 0
, O 0
dose O 0
- O 0
related O 0
changes O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
: O 0
decreases O 0
in O 0
LDL O 0
cholesterol B-Chemical 0
( O 0
24 O 0
% O 0
to O 0
40 O 0
% O 0
) O 0
and O 0
triglycerides B-Chemical 0
( O 0
9 O 0
% O 0
to O 0
18 O 0
% O 0
) O 0
, O 0
and O 0
increases O 0
in O 0
HDL O 0
cholesterol B-Chemical 0
( O 0
6 O 0
. O 0
7 O 0
% O 0
to O 0
8 O 0
. O 0
6 O 0
% O 0
) O 0
. O 0

Depending O 0
on O 0
the O 0
dose O 0
, O 0
from O 0
82 O 0
% O 0
to O 0
95 O 0
% O 0
of O 0
lovastatin B-Chemical 0
- O 0
treated O 0
women O 0
achieved O 0
the O 0
National O 0
Cholesterol B-Chemical 0
Education O 0
Program O 0
goal O 0
of O 0
LDL O 0
cholesterol B-Chemical 0
levels O 0
less O 0
than O 0
4 O 0
. O 0
14 O 0
mmol O 0
/ O 0
L O 0
( O 0
160 O 0
mg O 0
/ O 0
dL O 0
) O 0
, O 0
and O 0
40 O 0
% O 0
to O 0
87 O 0
% O 0
achieved O 0
the O 0
goal O 0
of O 0
3 O 0
. O 0
36 O 0
mmol O 0
/ O 0
L O 0
( O 0
130 O 0
mg O 0
/ O 0
dL O 0
) O 0
. O 0

Successive O 0
transaminase O 0
elevations O 0
greater O 0
than O 0
three 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
1 O 0
% O 0
of O 0
women O 0
and O 0
were O 0
dose O 0
dependent O 0
above O 0
the O 0
20 O 0
- O 0
mg O 0
dose O 0
. O 0

Myopathy B-Disease 0
, O 0
defined O 0
as O 0
muscle O 0
symptoms O 0
with O 0
creatine B-Chemical 0
kinase O 0
elevations O 0
greater O 0
than O 0
10 O 0
times O 0
the O 0
upper O 0
limit O 0
of O 0
normal O 0
, O 0
was O 0
rare O 0
and O 0
associated O 0
with O 0
the O 0
highest O 0
recommended O 0
daily O 0
dose O 0
of O 0
lovastatin B-Chemical 0
( O 0
80 O 0
mg O 0
) O 0
. O 0

Estrogen O 0
- O 0
replacement O 0
therapy O 0
appeared O 0
to O 0
have O 0
no O 0
effect O 0
on O 0
either O 0
the O 0
efficacy O 0
or O 0
safety O 0
profile O 0
of O 0
lovastatin B-Chemical 0
. O 0

CONCLUSION O 0
: O 0
Lovastatin B-Chemical 0
is O 0
highly O 0
effective O 0
and O 0
generally O 0
well O 0
tolerated O 0
as O 0
therapy O 0
for O 0
primary O 0
hypercholesterolemia B-Disease 0
in O 0
women O 0
. O 0

Tetany B-Disease 0
and O 0
rhabdomyolysis B-Disease 0
due O 0
to O 0
surreptitious O 0
furosemide B-Chemical 0
- O 0
- O 0
importance O 0
of O 0
magnesium B-Chemical 0
supplementation O 0
. O 0

Diuretics O 0
may O 0
induce O 0
hypokalemia B-Disease 0
, O 0
hypocalcemia B-Disease 0
and O 0
hypomagnesemia B-Disease 0
. O 0

While O 0
severe O 0
hypokalemia B-Disease 0
may O 0
cause O 0
muscle B-Disease 0
weakness I-Disease 0
, O 0
severe O 0
hypomagnesemia B-Disease 0
is O 0
associated O 0
with O 0
muscle B-Disease 0
spasms I-Disease 0
and O 0
tetany B-Disease 0
which O 0
cannot O 0
be O 0
corrected O 0
by O 0
potassium B-Chemical 0
and O 0
calcium B-Chemical 0
supplementation O 0
alone O 0
( O 0
1 O 0
, O 0
2 O 0
) O 0
. O 0

Surreptitious O 0
diuretic O 0
ingestion O 0
has O 0
been O 0
described O 0
, O 0
mainly O 0
in O 0
women O 0
who O 0
are O 0
concerned O 0
that O 0
they O 0
are O 0
obese B-Disease 0
or O 0
edematous B-Disease 0
. O 0

Symptomatic O 0
hypokalemia B-Disease 0
has O 0
been O 0
reported O 0
in O 0
such O 0
patients O 0
( O 0
3 O 0
- O 0
7 O 0
) O 0
and O 0
in O 0
one O 0
case O 0
hypocalcemia B-Disease 0
was O 0
observed O 0
( O 0
8 O 0
) O 0
, O 0
but O 0
the O 0
effects O 0
of O 0
magnesium B-Chemical 0
depletion O 0
were O 0
not O 0
noted O 0
in O 0
these O 0
patients O 0
. O 0

Ciprofloxacin B-Chemical 0
- O 0
induced O 0
nephrotoxicity B-Disease 0
in O 0
patients O 0
with O 0
cancer B-Disease 0
. O 0

Nephrotoxicity B-Disease 0
associated O 0
with O 0
ciprofloxacin B-Chemical 0
is O 0
uncommon O 0
. O 0

Five O 0
patients O 0
with O 0
cancer B-Disease 0
who O 0
developed O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
that O 0
followed O 0
treatment O 0
with O 0
ciprofloxacin B-Chemical 0
are O 0
described O 0
and O 0
an O 0
additional O 0
15 O 0
cases O 0
reported O 0
in O 0
the O 0
literature O 0
are O 0
reviewed O 0
. O 0

Other O 0
than O 0
elevation O 0
of O 0
serum O 0
creatinine B-Chemical 0
levels O 0
, O 0
characteristic O 0
clinical O 0
manifestations O 0
and O 0
abnormal O 0
laboratory O 0
findings O 0
are O 0
not O 0
frequently O 0
present O 0
. O 0

Allergic O 0
interstitial B-Disease 0
nephritis I-Disease 0
is O 0
believed O 0
to O 0
be O 0
the O 0
underlying O 0
pathological O 0
- O 0
process O 0
. O 0

Definitive O 0
diagnosis O 0
requires O 0
performance O 0
of O 0
renal O 0
biopsy O 0
, O 0
although O 0
this O 0
is O 0
not O 0
always O 0
feasible O 0
. O 0

An O 0
improvement O 0
in O 0
renal O 0
function O 0
that O 0
followed O 0
the O 0
discontinuation O 0
of O 0
the O 0
offending O 0
antibiotic O 0
supports O 0
the O 0
presumptive O 0
diagnosis O 0
of O 0
ciprofloxacin B-Chemical 0
- O 0
induced O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
. O 0

Venous B-Disease 0
complications I-Disease 0
of O 0
midazolam B-Chemical 0
versus O 0
diazepam B-Chemical 0
. O 0

Although O 0
some O 0
studies O 0
have O 0
suggested O 0
fewer O 0
venous B-Disease 0
complications I-Disease 0
are O 0
associated O 0
with O 0
midazolam B-Chemical 0
than O 0
with O 0
diazepam B-Chemical 0
for O 0
endoscopic O 0
procedures O 0
, O 0
this O 0
variable O 0
has O 0
not O 0
been O 0
well O 0
documented O 0
. O 0

We O 0
prospectively O 0
evaluated O 0
the O 0
incidence O 0
of O 0
venous B-Disease 0
complications I-Disease 0
after O 0
intravenous O 0
injection O 0
of O 0
diazepam B-Chemical 0
or O 0
midazolam B-Chemical 0
in O 0
122 O 0
consecutive O 0
patients O 0
undergoing O 0
colonoscopy O 0
and O 0
esophagogastroduodenoscopy O 0
. O 0

Overall O 0
, O 0
venous B-Disease 0
complications I-Disease 0
were O 0
more O 0
frequent O 0
with O 0
diazepam B-Chemical 0
( O 0
22 O 0
of O 0
62 O 0
patients O 0
) O 0
than O 0
with O 0
midazolam B-Chemical 0
( O 0
4 O 0
of O 0
60 O 0
patients O 0
) O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

A O 0
palpable O 0
venous O 0
cord O 0
was O 0
present O 0
in O 0
23 O 0
% O 0
( O 0
14 O 0
of O 0
62 O 0
) O 0
of O 0
patients O 0
in O 0
the O 0
diazepam B-Chemical 0
group O 0
, O 0
compared O 0
with O 0
2 O 0
% O 0
( O 0
1 O 0
of O 0
60 O 0
patients O 0
) O 0
in O 0
the O 0
midazolam B-Chemical 0
group O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
002 O 0
) O 0
. O 0

Pain B-Disease 0
at O 0
the O 0
injection O 0
site O 0
occurred O 0
in O 0
35 O 0
% O 0
( O 0
22 O 0
of O 0
62 O 0
) O 0
of O 0
patients O 0
in O 0
the O 0
diazepam B-Chemical 0
group O 0
compared O 0
with O 0
7 O 0
% O 0
( O 0
4 O 0
of O 0
60 O 0
patients O 0
) O 0
in O 0
the O 0
midazolam B-Chemical 0
group O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
. O 0

Swelling B-Disease 0
and O 0
warmth O 0
at O 0
the O 0
injection O 0
site O 0
were O 0
not O 0
significantly O 0
different O 0
between O 0
the O 0
two O 0
groups O 0
. O 0

Smoking O 0
, O 0
nonsteroidal O 0
anti O 0
- O 0
inflammatory O 0
drug O 0
use O 0
, O 0
intravenous O 0
catheter O 0
site O 0
, O 0
dwell O 0
time O 0
of O 0
the O 0
needle O 0
, O 0
alcohol B-Chemical 0
use O 0
, O 0
and O 0
pain B-Disease 0
during O 0
the O 0
injection O 0
had O 0
no O 0
effect O 0
on O 0
the O 0
incidence O 0
of O 0
venous B-Disease 0
complications I-Disease 0
. O 0

Clarithromycin B-Chemical 0
- O 0
associated O 0
visual B-Disease 0
hallucinations I-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
on O 0
continuous O 0
ambulatory O 0
peritoneal O 0
dialysis O 0
. O 0

Visual B-Disease 0
hallucinations I-Disease 0
are O 0
a O 0
rare O 0
event O 0
in O 0
chronic B-Disease 0
renal I-Disease 0
failure I-Disease 0
and O 0
not O 0
related O 0
to O 0
uremia B-Disease 0
per O 0
se O 0
. O 0

Unreported O 0
in O 0
the O 0
literature O 0
is O 0
visual B-Disease 0
hallucinations I-Disease 0
occurring O 0
in O 0
association O 0
with O 0
the O 0
new O 0
macrolide B-Chemical 0
antibiotic O 0
, O 0
clarithromycin B-Chemical 0
. O 0

We O 0
describe O 0
such O 0
a O 0
case O 0
in O 0
a O 0
patient O 0
with 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
maintained O 0
on O 0
continuous O 0
ambulatory O 0
peritoneal O 0
dialysis O 0
( O 0
CAPD O 0
) O 0
. O 0

The O 0
combination O 0
of O 0
a O 0
relatively O 0
high O 0
dose O 0
of O 0
clarithromycin B-Chemical 0
in O 0
face O 0
of O 0
chronic B-Disease 0
renal I-Disease 0
failure I-Disease 0
in O 0
a O 0
functionally O 0
anephric O 0
patient O 0
, O 0
with O 0
underlying O 0
aluminum B-Chemical 0
intoxication O 0
, O 0
may O 0
have O 0
facilitated O 0
the O 0
appearance O 0
of O 0
this O 0
neurotoxic B-Disease 0
side O 0
effect O 0
. O 0

It O 0
is O 0
important O 0
to O 0
understand O 0
the O 0
pharmacokinetics O 0
of O 0
medications O 0
in O 0
face O 0
of O 0
chronic B-Disease 0
renal I-Disease 0
failure I-Disease 0
, O 0
the O 0
possibility O 0
of O 0
drug O 0
interactions O 0
, O 0
and O 0
how O 0
these O 0
factors O 0
should O 0
help O 0
guide O 0
medication O 0
therapy O 0
in O 0
the O 0
ESRD B-Disease 0
patient O 0
. O 0

Changes O 0
in O 0
peroxisomes O 0
in O 0
preneoplastic O 0
liver O 0
and O 0
hepatoma B-Disease 0
of O 0
mice O 0
induced O 0
by O 0
alpha B-Chemical 0
- I-Chemical 0
benzene I-Chemical 0
hexachloride I-Chemical 0
. O 0

Peroxisomes O 0
in O 0
hepatomas B-Disease 0
and O 0
hyperplastic O 0
preneoplastic O 0
liver B-Disease 0
lesions I-Disease 0
induced O 0
in O 0
mice O 0
by O 0
500 O 0
ppm O 0
alpha B-Chemical 0
- I-Chemical 0
benzene I-Chemical 0
hexachloride I-Chemical 0
were O 0
examined O 0
histochemically O 0
and O 0
electron O 0
microscopically O 0
. O 0

Although O 0
most O 0
of O 0
the O 0
hepatomas B-Disease 0
were O 0
well O 0
- O 0
differentiated O 0
tumors B-Disease 0
and O 0
contained O 0
a O 0
considerable O 0
number O 0
of O 0
peroxisomes O 0
, O 0
the O 0
tumor B-Disease 0
cells O 0
did O 0
not O 0
respond O 0
to O 0
ethyl B-Chemical 0
- I-Chemical 0
alpha I-Chemical 0
- I-Chemical 0
p I-Chemical 0
- I-Chemical 0
chlorophenoxyisobutyrate I-Chemical 0
with O 0
proliferation O 0
of O 0
peroxisomes O 0
. O 0

At O 0
the O 0
16th O 0
week O 0
of O 0
carcinogen O 0
feeding O 0
, O 0
hyperplastic O 0
nodules O 0
appeared O 0
and O 0
advanced O 0
to O 0
further O 0
stages O 0
. O 0

A O 0
majority O 0
of O 0
the O 0
nodules O 0
showed O 0
a O 0
considerable O 0
number O 0
of O 0
peroxisomes O 0
and O 0
the O 0
inductive O 0
proliferation O 0
of O 0
peroxisomes O 0
. O 0

Within O 0
the O 0
nodules O 0
, O 0
foci O 0
of O 0
proliferation O 0
of O 0
the O 0
cells O 0
that O 0
showed O 0
no O 0
inducibility O 0
of O 0
proliferation O 0
of O 0
peroxisomes O 0
appeared O 0
. O 0

These O 0
cells O 0
proliferated O 0
further O 0
, O 0
replacing O 0
the O 0
most O 0
part O 0
of O 0
the O 0
nodules O 0
, O 0
and O 0
with O 0
this O 0
process O 0
hepatomas B-Disease 0
appeared O 0
to O 0
have O 0
been O 0
formed O 0
. O 0

No O 0
abnormal O 0
matrical O 0
inclusions O 0
of O 0
peroxisomes O 0
were O 0
formed O 0
in O 0
the O 0
cells O 0
of O 0
hyperplastic O 0
nodules O 0
by O 0
ethyl B-Chemical 0
- I-Chemical 0
alpha I-Chemical 0
- I-Chemical 0
p I-Chemical 0
- I-Chemical 0
chlorophenoxyisobutyrate I-Chemical 0
unlike O 0
in O 0
the O 0
case O 0
of O 0
rats O 0
. O 0

Contribution O 0
of O 0
the O 0
sympathetic O 0
nervous O 0
system O 0
to O 0
salt O 0
- O 0
sensitivity O 0
in O 0
lifetime O 0
captopril B-Chemical 0
- O 0
treated O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
test O 0
the O 0
hypothesis O 0
that O 0
, O 0
in O 0
lifetime O 0
captopril B-Chemical 0
- O 0
treated O 0
spontaneously O 0
hypertensive B-Disease 0
rats O 0
( O 0
SHR O 0
) O 0
, O 0
the O 0
sympathetic O 0
nervous O 0
system O 0
contributes O 0
importantly O 0
to O 0
the O 0
hypertensive B-Disease 0
effect O 0
of O 0
dietary B-Chemical 0
sodium I-Chemical 0
chloride I-Chemical 0
supplementation O 0
. O 0

METHODS O 0
: O 0
Male O 0
SHR O 0
( O 0
aged O 0
6 O 0
weeks O 0
) O 0
that O 0
had O 0
been O 0
treated O 0
from O 0
conception O 0
onward O 0
with O 0
either O 0
captopril B-Chemical 0
or O 0
vehicle O 0
remained O 0
on O 0
a O 0
basal O 0
sodium B-Chemical 0
chloride I-Chemical 0
diet O 0
or O 0
were O 0
fed O 0
a O 0
high O 0
sodium B-Chemical 0
chloride I-Chemical 0
diet O 0
. O 0

After O 0
2 O 0
weeks O 0
, O 0
the O 0
rats O 0
were O 0
subjected O 0
to O 0
ganglionic O 0
blockade O 0
and O 0
2 O 0
days O 0
later O 0
, O 0
an O 0
infusion O 0
of O 0
clonidine B-Chemical 0
. O 0

RESULTS O 0
: O 0
Lifetime O 0
captopril B-Chemical 0
treatment O 0
significantly O 0
lowered O 0
mean O 0
arterial O 0
pressure O 0
in O 0
both O 0
groups O 0
. O 0

Intravenous O 0
infusion O 0
of O 0
the O 0
ganglionic O 0
blocker O 0
hexamethonium B-Chemical 0
resulted O 0
in O 0
a O 0
rapid O 0
decline O 0
in O 0
MAP O 0
that O 0
eliminated O 0
the O 0
dietary B-Chemical 0
sodium I-Chemical 0
chloride I-Chemical 0
- O 0
induced O 0
increase B-Disease 0
in I-Disease 0
MAP I-Disease 0
in O 0
both O 0
groups O 0
. O 0

Infusion O 0
of O 0
the O 0
central O 0
nervous O 0
system O 0
alpha2 B-Chemical 0
- I-Chemical 0
adrenergic I-Chemical 0
receptor I-Chemical 0
agonist I-Chemical 0
clonidine B-Chemical 0
also O 0
resulted O 0
in O 0
a O 0
greater O 0
reduction O 0
in O 0
MAP O 0
in O 0
both O 0
groups O 0
of O 0
SHR O 0
that O 0
were O 0
fed O 0
the O 0
high O 0
( O 0
compared O 0
with O 0
the O 0
basal O 0
) O 0
sodium B-Chemical 0
chloride I-Chemical 0
diet O 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
both O 0
lifetime O 0
captopril B-Chemical 0
- O 0
treated O 0
and O 0
control O 0
SHR O 0
, O 0
the O 0
sympathetic O 0
nervous O 0
system O 0
contributes O 0
to O 0
the O 0
pressor O 0
effects O 0
of O 0
a O 0
high O 0
sodium B-Chemical 0
chloride I-Chemical 0
diet O 0
. O 0

Angioedema B-Disease 0
associated O 0
with O 0
droperidol B-Chemical 0
administration O 0
. O 0

Angioedema B-Disease 0
, O 0
also O 0
known O 0
as O 0
angioneurotic B-Disease 0
edema I-Disease 0
or O 0
Quincke B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
, O 0
is O 0
a O 0
well O 0
- O 0
demarcated O 0
, O 0
localized O 0
edema B-Disease 0
involving O 0
the O 0
subcutaneous O 0
tissues O 0
that O 0
may O 0
cause O 0
upper B-Disease 0
- I-Disease 0
airway I-Disease 0
obstruction I-Disease 0
. O 0

We O 0
report O 0
the O 0
case O 0
of O 0
a O 0
previously O 0
healthy O 0
19 O 0
- O 0
year O 0
- O 0
old O 0
man O 0
with O 0
no O 0
known O 0
drug B-Disease 0
allergies I-Disease 0
in O 0
whom O 0
angioedema B-Disease 0
with O 0
significant O 0
tongue B-Disease 0
swelling I-Disease 0
and O 0
protrusion O 0
developed O 0
within O 0
10 O 0
minutes O 0
of O 0
the O 0
administration O 0
of O 0
a O 0
single O 0
IV O 0
dose O 0
of O 0
droperidol B-Chemical 0
. O 0

Late O 0
cardiotoxicity B-Disease 0
after O 0
treatment O 0
for O 0
a O 0
malignant O 0
bone B-Disease 0
tumor I-Disease 0
. O 0

Cardiac O 0
function O 0
was O 0
assessed O 0
in O 0
long O 0
- O 0
term O 0
survivors O 0
of O 0
malignant O 0
bone B-Disease 0
tumors I-Disease 0
who O 0
were O 0
treated O 0
according O 0
to O 0
Rosen B-Chemical 0
' I-Chemical 0
s I-Chemical 0
T5 I-Chemical 0
or I-Chemical 0
T10 I-Chemical 0
protocol I-Chemical 0
, O 0
both O 0
including O 0
doxorubicin B-Chemical 0
. O 0

Thirty O 0
- O 0
one O 0
patients O 0
, O 0
age O 0
10 O 0
- O 0
45 O 0
years O 0
( O 0
median O 0
age O 0
17 O 0
. O 0
8 O 0
years O 0
) O 0
were O 0
evaluated O 0
2 O 0
. O 0
3 O 0
- O 0
14 O 0
. O 0
1 O 0
years O 0
( O 0
median O 0
8 O 0
. O 0
9 O 0
years O 0
) O 0
following O 0
completion O 0
of O 0
treatment O 0
. O 0

Cumulative O 0
doses O 0
of O 0
doxorubicin B-Chemical 0
were O 0
225 O 0
- O 0
550 O 0
mg O 0
/ O 0
m2 O 0
( O 0
median O 0
dose O 0
360 O 0
) O 0
. O 0

The O 0
evaluation O 0
consisted O 0
of O 0
a O 0
history O 0
, O 0
physical O 0
examination O 0
, O 0
electrocardiogram O 0
( O 0
ECG O 0
) O 0
, O 0
signal O 0
averaged O 0
ECG O 0
, O 0
24 O 0
- O 0
hour O 0
ambulatory O 0
ECG O 0
, O 0
echocardiography O 0
and O 0
radionuclide O 0
angiography O 0
. O 0

Eighteen O 0
of O 0
31 O 0
( O 0
58 O 0
% O 0
) O 0
patients O 0
showed O 0
cardiac B-Disease 0
toxicity I-Disease 0
, O 0
defined O 0
as O 0
having O 0
one O 0
or O 0
more O 0
of O 0
the O 0
following O 0
abnormalities O 0
: O 0
late O 0
potentials O 0
, O 0
complex O 0
ventricular B-Disease 0
arrhythmias I-Disease 0
, O 0
left O 0
ventricular B-Disease 0
dilation I-Disease 0
, O 0
decreased O 0
shortening O 0
fraction O 0
, O 0
or O 0
decreased O 0
ejection O 0
fraction O 0
. O 0

The O 0
incidence O 0
of O 0
cardiac B-Disease 0
abnormalities I-Disease 0
increased O 0
with O 0
length O 0
of O 0
follow O 0
- O 0
up O 0
( O 0
P O 0
< O 0
or O 0
= O 0
. O 0
05 O 0
) O 0
. O 0

No O 0
correlation O 0
could O 0
be O 0
demonstrated O 0
between O 0
cumulative O 0
dose O 0
of O 0
doxorubicin B-Chemical 0
and O 0
cardiac O 0
status O 0
, O 0
except O 0
for O 0
heart O 0
rate O 0
variability O 0
. O 0

When O 0
adjusted O 0
to O 0
body O 0
surface O 0
area O 0
, O 0
the O 0
left O 0
ventricular O 0
posterior O 0
wall O 0
thickness O 0
( O 0
LVPW O 0
index O 0
) O 0
was O 0
decreased O 0
in O 0
all O 0
patients O 0
. O 0

The O 0
incidence O 0
of O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
is O 0
high O 0
and O 0
increases O 0
with O 0
follow O 0
- O 0
up O 0
, O 0
irrespective O 0
of O 0
cumulative O 0
dose O 0
. O 0

Life O 0
- O 0
long O 0
cardiac O 0
follow O 0
- O 0
up O 0
in O 0
these O 0
patients O 0
is O 0
warranted O 0
. O 0

The O 0
results O 0
of O 0
our O 0
study O 0
suggest O 0
that O 0
heart O 0
rate O 0
variability O 0
and O 0
LVPW O 0
index O 0
could O 0
be O 0
sensitive O 0
indicators O 0
for O 0
cardiotoxicity B-Disease 0
. O 0

Acute O 0
blood O 0
pressure O 0
elevations O 0
with O 0
caffeine B-Chemical 0
in O 0
men O 0
with O 0
borderline O 0
systemic O 0
hypertension B-Disease 0
. O 0

Whether O 0
the O 0
vasoconstrictive O 0
actions O 0
of O 0
caffeine B-Chemical 0
are O 0
enhanced O 0
in O 0
hypertensive B-Disease 0
persons O 0
has O 0
not O 0
been O 0
demonstrated O 0
. O 0

Thus O 0
, O 0
caffeine B-Chemical 0
( O 0
3 O 0
. O 0
3 O 0
mg O 0
/ O 0
kg O 0
) O 0
versus O 0
placebo O 0
was O 0
tested O 0
in O 0
48 O 0
healthy O 0
men O 0
( O 0
aged O 0
20 O 0
to O 0
35 O 0
years O 0
) O 0
selected O 0
after O 0
screening O 0
on O 0
2 O 0
separate O 0
occasions O 0
. O 0

Borderline O 0
hypertensive B-Disease 0
men O 0
( O 0
n O 0
= O 0
24 O 0
) O 0
were O 0
selected O 0
with O 0
screening O 0
systolic O 0
blood O 0
pressure O 0
( O 0
BP O 0
) O 0
of O 0
140 O 0
to O 0
160 O 0
mm O 0
Hg O 0
and O 0
/ O 0
or O 0
diastolic O 0
BP O 0
90 O 0
to O 0
99 O 0
mm O 0
Hg O 0
. O 0

Low O 0
- O 0
risk O 0
controls O 0
( O 0
n O 0
= O 0
24 O 0
) O 0
reported O 0
no O 0
parental O 0
history O 0
of O 0
hypertension B-Disease 0
and O 0
had O 0
screening O 0
BP O 0
< O 0
130 O 0
/ O 0
85 O 0
mm O 0
Hg O 0
. O 0

Participants O 0
were O 0
then O 0
tested O 0
on O 0
2 O 0
occasions O 0
after O 0
12 O 0
- O 0
hour O 0
abstinence O 0
from O 0
caffeine B-Chemical 0
in O 0
each O 0
of O 0
2 O 0
protocols O 0
; O 0
this O 0
required O 0
a O 0
total O 0
of O 0
4 O 0
laboratory O 0
visits O 0
. O 0

Caffeine B-Chemical 0
- O 0
induced O 0
changes O 0
in O 0
diastolic O 0
BP O 0
were O 0
2 O 0
to O 0
3 O 0
times O 0
larger O 0
in O 0
borderline O 0
subjects O 0
than O 0
in O 0
controls O 0
( O 0
+ O 0
8 O 0
. O 0
4 O 0
vs O 0
+ O 0
3 O 0
. O 0
8 O 0
mm O 0
Hg O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
0001 O 0
) O 0
, O 0
and O 0
were O 0
attributable O 0
to O 0
larger O 0
changes O 0
in O 0
impedance O 0
- O 0
derived O 0
measures O 0
of O 0
systemic O 0
vascular O 0
resistance O 0
( O 0
+ O 0
135 O 0
vs O 0
+ O 0
45 O 0
dynes O 0
. O 0
s O 0
. O 0
cm O 0
- O 0
5 O 0
, O 0
p O 0
< O 0
0 O 0
. O 0
004 O 0
) O 0
. O 0

These O 0
findings O 0
were O 0
consistent O 0
and O 0
reached O 0
significance O 0
in O 0
both O 0
protocols O 0
. O 0

The O 0
percentage O 0
of O 0
borderline O 0
subjects O 0
in O 0
whom O 0
diastolic O 0
BP O 0
changes O 0
exceeded O 0
the O 0
median O 0
control O 0
response O 0
was O 0
96 O 0
% O 0
. O 0

Consequently O 0
, O 0
whereas O 0
all O 0
participants O 0
exhibited O 0
normotensive O 0
levels O 0
during O 0
the O 0
resting O 0
predrug O 0
baseline O 0
, O 0
33 O 0
% O 0
of O 0
borderline O 0
subjects O 0
achieved O 0
hypertensive B-Disease 0
BP O 0
levels O 0
after O 0
caffeine B-Chemical 0
ingestion O 0
. O 0

Thus O 0
, O 0
in O 0
borderline O 0
hypertensive B-Disease 0
men O 0
, O 0
exaggerated O 0
responses O 0
to O 0
caffeine B-Chemical 0
were O 0
: O 0
selective O 0
for O 0
diastolic O 0
BP O 0
, O 0
consistent O 0
with O 0
greater O 0
vasoconstriction O 0
, O 0
replicated O 0
in O 0
2 O 0
protocols O 0
, O 0
and O 0
representative O 0
of O 0
nearly O 0
all O 0
borderline O 0
hypertensives B-Disease 0
. O 0

We O 0
suspect O 0
that O 0
the O 0
potential O 0
for O 0
caffeine B-Chemical 0
to O 0
stabilize O 0
high O 0
resistance O 0
states O 0
in O 0
susceptible O 0
persons O 0
suggests O 0
that O 0
its O 0
use O 0
may O 0
facilitate O 0
their O 0
disease O 0
progression O 0
, O 0
as O 0
well O 0
as O 0
hinder O 0
accurate O 0
diagnosis O 0
and O 0
treatment O 0
. O 0

Absence O 0
of O 0
effect O 0
of O 0
sertraline B-Chemical 0
on O 0
time O 0
- O 0
based O 0
sensitization O 0
of O 0
cognitive B-Disease 0
impairment I-Disease 0
with O 0
haloperidol B-Chemical 0
. O 0

This O 0
double O 0
- O 0
blind O 0
, O 0
randomized O 0
, O 0
placebo O 0
- O 0
controlled O 0
study O 0
evaluated O 0
the O 0
effects O 0
of O 0
haloperidol B-Chemical 0
alone O 0
and O 0
haloperidol B-Chemical 0
plus O 0
sertraline B-Chemical 0
on O 0
cognitive O 0
and O 0
psychomotor O 0
function O 0
in O 0
24 O 0
healthy O 0
male O 0
subjects O 0
. O 0

METHOD O 0
: O 0
All O 0
subjects O 0
received O 0
placebo O 0
on O 0
Day O 0
1 O 0
and O 0
haloperidol B-Chemical 0
2 O 0
mg O 0
on O 0
Days O 0
2 O 0
and O 0
25 O 0
. O 0

From O 0
Days O 0
9 O 0
to O 0
25 O 0
, O 0
subjects O 0
were O 0
randomly O 0
assigned O 0
to O 0
either O 0
sertraline B-Chemical 0
( O 0
12 O 0
subjects O 0
) O 0
or O 0
placebo O 0
( O 0
12 O 0
subjects O 0
) O 0
; O 0
the O 0
sertraline B-Chemical 0
dose O 0
was O 0
titrated O 0
from O 0
50 O 0
to O 0
200 O 0
mg O 0
/ O 0
day O 0
from O 0
Days O 0
9 O 0
to O 0
16 O 0
, O 0
and O 0
remained O 0
at O 0
200 O 0
mg O 0
/ O 0
day O 0
for O 0
the O 0
final O 0
10 O 0
days O 0
of O 0
the O 0
drug O 0
administration O 0
period O 0
. O 0

Cognitive O 0
function O 0
testing O 0
was O 0
performed O 0
before O 0
dosing O 0
and O 0
over O 0
a O 0
24 O 0
- O 0
hour O 0
period O 0
after O 0
dosing O 0
on O 0
Days O 0
1 O 0
, O 0
2 O 0
, O 0
and O 0
25 O 0
. O 0

RESULTS O 0
: O 0
Impairment B-Disease 0
of I-Disease 0
cognitive I-Disease 0
function I-Disease 0
was O 0
observed O 0
6 O 0
to O 0
8 O 0
hours O 0
after O 0
administration O 0
of O 0
haloperidol B-Chemical 0
on O 0
Day O 0
2 O 0
but O 0
was O 0
not O 0
evident O 0
23 O 0
hours O 0
after O 0
dosing O 0
. O 0

When O 0
single O 0
- O 0
dose O 0
haloperidol B-Chemical 0
was O 0
given O 0
again O 0
25 O 0
days O 0
later O 0
, O 0
greater O 0
impairment O 0
with O 0
earlier O 0
onset O 0
was O 0
noted O 0
in O 0
several O 0
tests O 0
in O 0
both O 0
treatment O 0
groups O 0
, O 0
suggesting O 0
enhancement O 0
of O 0
this O 0
effect O 0
. O 0

There O 0
was O 0
no O 0
indication O 0
that O 0
sertraline B-Chemical 0
exacerbated O 0
the O 0
impairment O 0
produced O 0
by O 0
haloperidol B-Chemical 0
since O 0
an O 0
equivalent O 0
effect O 0
also O 0
occurred O 0
in O 0
the O 0
placebo O 0
group O 0
. O 0

Three O 0
subjects O 0
( O 0
2 O 0
on O 0
sertraline B-Chemical 0
and O 0
1 O 0
on O 0
placebo O 0
) O 0
withdrew O 0
from O 0
the O 0
study O 0
because O 0
of O 0
side O 0
effects O 0
. O 0

Ten O 0
subjects O 0
in O 0
each O 0
group O 0
reported O 0
side O 0
effects O 0
related O 0
to O 0
treatment O 0
. O 0

The O 0
side O 0
effect O 0
profiles O 0
of O 0
sertraline B-Chemical 0
and O 0
of O 0
placebo O 0
were O 0
similar O 0
. O 0

CONCLUSION O 0
: O 0
Haloperidol B-Chemical 0
produced O 0
a O 0
clear O 0
profile O 0
of O 0
cognitive B-Disease 0
impairment I-Disease 0
that O 0
was O 0
not O 0
worsened O 0
by O 0
concomitant O 0
sertraline B-Chemical 0
administration O 0
. O 0

Coexistence O 0
of O 0
cerebral B-Disease 0
venous I-Disease 0
sinus I-Disease 0
and I-Disease 0
internal I-Disease 0
carotid I-Disease 0
artery I-Disease 0
thrombosis I-Disease 0
associated O 0
with O 0
exogenous O 0
sex O 0
hormones O 0
. O 0

A O 0
case O 0
report O 0
. O 0

A O 0
forty O 0
- O 0
six O 0
year O 0
- O 0
old O 0
premenopausal O 0
woman O 0
developed O 0
headache B-Disease 0
, O 0
nausea B-Disease 0
and O 0
vomiting B-Disease 0
, O 0
left O 0
hemiparesis B-Disease 0
and O 0
seizure B-Disease 0
two O 0
days O 0
after O 0
parenteral O 0
use O 0
of O 0
progesterone B-Chemical 0
and O 0
estradiol B-Chemical 0
. O 0

Diabetes B-Disease 0
mellitus I-Disease 0
( O 0
DM B-Disease 0
) O 0
was O 0
found O 0
during O 0
admission O 0
. O 0

Computed O 0
tomography O 0
showed O 0
a O 0
hemorrhagic B-Disease 0
infarct I-Disease 0
in O 0
the O 0
right O 0
frontal O 0
lobe O 0
and O 0
increased O 0
density O 0
in O 0
the O 0
superior O 0
sagittal O 0
sinus O 0
( O 0
SSS O 0
) O 0
. O 0

Left O 0
carotid O 0
angiography O 0
found O 0
occlusion B-Disease 0
of I-Disease 0
the I-Disease 0
left I-Disease 0
internal I-Disease 0
carotid I-Disease 0
artery I-Disease 0
( O 0
ICA O 0
) O 0
. O 0

Right O 0
carotid O 0
angiograms O 0
failed O 0
to O 0
show O 0
the O 0
SSS O 0
and O 0
inferior O 0
sagittal O 0
sinus O 0
, O 0
suggestive O 0
of O 0
venous B-Disease 0
sinus I-Disease 0
thrombosis I-Disease 0
. O 0

Coexistence O 0
of O 0
the O 0
cerebral B-Disease 0
artery I-Disease 0
and I-Disease 0
the I-Disease 0
venous I-Disease 0
sinus I-Disease 0
occlusion I-Disease 0
has O 0
been O 0
described O 0
infrequently O 0
. O 0

In O 0
this O 0
case O 0
, O 0
the O 0
authors O 0
postulate O 0
that O 0
the O 0
use O 0
of O 0
estradiol B-Chemical 0
and O 0
progesterone B-Chemical 0
and O 0
the O 0
underlying O 0
DM B-Disease 0
increased O 0
vascular O 0
thrombogenicity O 0
, O 0
which O 0
provided O 0
a O 0
common O 0
denominator O 0
for O 0
thrombosis B-Disease 0
of I-Disease 0
both I-Disease 0
the I-Disease 0
ICA I-Disease 0
and I-Disease 0
the I-Disease 0
venous I-Disease 0
sinus I-Disease 0
. O 0

Chemotherapy O 0
of O 0
advanced O 0
inoperable 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
with O 0
paclitaxel B-Chemical 0
: O 0
a O 0
phase O 0
II O 0
trial 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
has O 0
demonstrated O 0
significant O 0
antineoplastic O 0
activity O 0
against O 0
different O 0
tumor B-Disease 0
types O 0
, O 0
notably O 0
ovarian B-Disease 0
and I-Disease 0
breast I-Disease 0
carcinoma I-Disease 0
. O 0

Two O 0
phase O 0
II O 0
trials O 0
of O 0
24 O 0
- O 0
hour O 0
paclitaxel B-Chemical 0
infusions O 0
in O 0
chemotherapy O 0
- O 0
naive O 0
patients O 0
with O 0
stage O 0
IIIB O 0
or O 0
IV 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
NSCLC B-Disease 0
) O 0
reported O 0
response O 0
rates O 0
of O 0
21 O 0
% O 0
and O 0
24 O 0
% O 0
. O 0

Leukopenia B-Disease 0
was O 0
dose O 0
limiting O 0
: O 0
as O 0
many O 0
as O 0
62 O 0
. O 0
5 O 0
% O 0
of O 0
patients O 0
experienced O 0
grade O 0
4 O 0
leukopenia B-Disease 0
. O 0

We O 0
investigated O 0
the O 0
efficacy O 0
and O 0
toxicity B-Disease 0
of O 0
a O 0
3 O 0
- O 0
hour O 0
paclitaxel B-Chemical 0
infusion O 0
in O 0
a O 0
phase O 0
II O 0
trial O 0
in O 0
patients O 0
with O 0
inoperable O 0
stage O 0
IIIB O 0
or O 0
IV O 0
NSCLC B-Disease 0
. O 0

The O 0
58 O 0
patients O 0
treated O 0
( O 0
41 O 0
men O 0
and O 0
17 O 0
women O 0
) O 0
had O 0
a O 0
median O 0
age O 0
of O 0
59 O 0
years O 0
( O 0
age O 0
range O 0
, O 0
25 O 0
to O 0
75 O 0
) O 0
and O 0
a O 0
performance O 0
status O 0
of O 0
0 O 0
through O 0
2 O 0
. O 0

Most O 0
patients O 0
( O 0
72 O 0
. O 0
4 O 0
% O 0
) O 0
had O 0
stage O 0
IV O 0
NSCLC B-Disease 0
. O 0

Paclitaxel B-Chemical 0
225 O 0
mg O 0
/ O 0
m2 O 0
was O 0
infused O 0
over O 0
3 O 0
hours O 0
every O 0
3 O 0
weeks O 0
with O 0
standard O 0
prophylactic O 0
premedication O 0
. O 0

Of O 0
50 O 0
patients O 0
evaluable O 0
for O 0
response O 0
, O 0
12 O 0
( O 0
24 O 0
% O 0
) O 0
had O 0
partial O 0
remission O 0
, O 0
26 O 0
( O 0
52 O 0
% O 0
) O 0
had O 0
no O 0
change O 0
, O 0
and O 0
12 O 0
had O 0
disease O 0
progression O 0
( O 0
24 O 0
% O 0
) O 0
. O 0

Hematologic O 0
toxicities B-Disease 0
were O 0
mild O 0
: O 0
only O 0
one O 0
patient O 0
( O 0
2 O 0
% O 0
) O 0
developed O 0
grade O 0
3 O 0
or O 0
4 O 0
neutropenia B-Disease 0
, O 0
while O 0
29 O 0
% O 0
had O 0
grade O 0
1 O 0
or O 0
2 O 0
. O 0

Grade O 0
1 O 0
or O 0
2 O 0
polyneuropathy B-Disease 0
affected O 0
56 O 0
% O 0
of O 0
patients O 0
while O 0
only O 0
one O 0
( O 0
2 O 0
% O 0
) O 0
experienced O 0
severe O 0
polyneuropathy B-Disease 0
. O 0

Similarly O 0
, O 0
grade O 0
1 O 0
or O 0
2 O 0
myalgia B-Disease 0
/ O 0
arthralgia B-Disease 0
was O 0
observed O 0
in O 0
63 O 0
. O 0
2 O 0
% O 0
of O 0
patients O 0
, O 0
but O 0
only O 0
14 O 0
. O 0
3 O 0
% O 0
experienced O 0
grade O 0
3 O 0
or O 0
4 O 0
. O 0

Nausea B-Disease 0
and O 0
vomiting B-Disease 0
were O 0
infrequent O 0
, O 0
with O 0
14 O 0
% O 0
of O 0
patients O 0
experiencing O 0
grade O 0
1 O 0
or O 0
2 O 0
and O 0
only O 0
2 O 0
% O 0
experiencing O 0
grade O 0
3 O 0
or O 0
4 O 0
. O 0

Paclitaxel B-Chemical 0
is O 0
thus O 0
an O 0
active O 0
single O 0
agent O 0
in O 0
this O 0
patient O 0
population O 0
, O 0
with O 0
a O 0
3 O 0
- O 0
hour O 0
infusion O 0
proving O 0
comparably O 0
effective O 0
to O 0
a O 0
24 O 0
- O 0
hour O 0
infusion O 0
and O 0
superior O 0
in O 0
terms O 0
of O 0
the O 0
incidence O 0
of O 0
hematologic O 0
and O 0
nonhematologic O 0
toxicity B-Disease 0
. O 0

Further O 0
phase O 0
II O 0
studies O 0
with O 0
paclitaxel B-Chemical 0
combined O 0
with O 0
other O 0
drugs O 0
active O 0
against O 0
NSCLC B-Disease 0
are O 0
indicated O 0
, O 0
and O 0
phase O 0
III O 0
studies O 0
comparing O 0
paclitaxel B-Chemical 0
with O 0
standard O 0
chemotherapy O 0
remain O 0
to O 0
be O 0
completed O 0
. O 0

Paclitaxel B-Chemical 0
combined O 0
with O 0
carboplatin B-Chemical 0
in O 0
the O 0
first O 0
- O 0
line O 0
treatment O 0
of O 0
advanced O 0
ovarian B-Disease 0
cancer I-Disease 0
. O 0

In O 0
a O 0
phase O 0
I O 0
study O 0
to O 0
determine O 0
the O 0
maximum O 0
tolerated O 0
dose O 0
of 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
given O 0
as O 0
a O 0
3 O 0
- O 0
hour O 0
infusion O 0
in O 0
combination O 0
with O 0
carboplatin B-Chemical 0
administered O 0
every O 0
21 O 0
days O 0
to O 0
women O 0
with O 0
advanced O 0
ovarian B-Disease 0
cancer I-Disease 0
, O 0
paclitaxel B-Chemical 0
doses O 0
were O 0
escalated O 0
as O 0
follows O 0
: O 0
level O 0
1 O 0
, O 0
135 O 0
mg O 0
/ O 0
m2 O 0
; O 0
level O 0
2 O 0
, O 0
160 O 0
mg O 0
/ O 0
m2 O 0
; O 0
level O 0
3 O 0
, O 0
185 O 0
mg O 0
/ O 0
m2 O 0
; O 0
and O 0
level O 0
4 O 0
, O 0
210 O 0
mg O 0
/ O 0
m2 O 0
. O 0

The O 0
fixed O 0
dose O 0
of O 0
carboplatin B-Chemical 0
at O 0
levels O 0
1 O 0
through O 0
4 O 0
was O 0
given O 0
to O 0
achieve O 0
an O 0
area O 0
under O 0
the O 0
concentration O 0
- O 0
time O 0
curve O 0
( O 0
AUC O 0
) O 0
of O 0
5 O 0
using O 0
the O 0
Calvert O 0
formula O 0
. O 0

In O 0
levels O 0
5 O 0
and O 0
6 O 0
the O 0
carboplatin B-Chemical 0
dose O 0
was O 0
targeted O 0
at O 0
AUCs O 0
of O 0
6 O 0
and O 0
7 O 0
. O 0
5 O 0
, O 0
respectively O 0
, O 0
combined O 0
with O 0
a O 0
fixed O 0
paclitaxel B-Chemical 0
dose O 0
of O 0
185 O 0
mg O 0
/ O 0
m2 O 0
. O 0

To O 0
date O 0
, O 0
30 O 0
previously O 0
untreated O 0
patients O 0
, O 0
all O 0
with O 0
a O 0
good O 0
performance O 0
status O 0
( O 0
Eastern O 0
Cooperative O 0
Oncology O 0
Group O 0
0 O 0
to O 0
2 O 0
) O 0
have O 0
been O 0
entered O 0
into O 0
this O 0
ongoing O 0
study O 0
. O 0

The O 0
dose O 0
- O 0
limiting O 0
toxicity B-Disease 0
of O 0
the O 0
combination O 0
was O 0
myelosuppression B-Disease 0
( O 0
leukopenia B-Disease 0
, O 0
granulocytopenia B-Disease 0
, O 0
and O 0
thrombocytopenia B-Disease 0
) O 0
. O 0

Neurotoxicity B-Disease 0
was O 0
largely O 0
moderate O 0
. O 0

So O 0
far O 0
, O 0
14 O 0
patients O 0
are O 0
evaluable O 0
for O 0
response O 0
; O 0
of O 0
these O 0
, O 0
eight O 0
( O 0
57 O 0
% O 0
) O 0
showed O 0
objective O 0
( O 0
complete O 0
or O 0
partial O 0
) O 0
response O 0
and O 0
disease O 0
stabilized O 0
in O 0
six O 0
patients O 0
. O 0

No O 0
patient O 0
had O 0
disease O 0
progression O 0
. O 0

We O 0
conclude O 0
that O 0
the O 0
combination O 0
of O 0
paclitaxel B-Chemical 0
185 O 0
mg O 0
/ O 0
m2 O 0
administered O 0
as O 0
a O 0
3 O 0
- O 0
hour O 0
infusion O 0
followed O 0
immediately O 0
by O 0
a O 0
1 O 0
- O 0
hour O 0
infusion O 0
of O 0
carboplatin B-Chemical 0
at O 0
an O 0
AUC O 0
of O 0
6 O 0
can O 0
be O 0
administered O 0
safely O 0
in O 0
a O 0
21 O 0
- O 0
day O 0
schedule O 0
in O 0
the O 0
outpatient O 0
setting O 0
. O 0

The O 0
recommended O 0
dose O 0
for O 0
phase O 0
III O 0
studies O 0
is O 0
paclitaxel B-Chemical 0
185 O 0
mg O 0
/ O 0
m2 O 0
and O 0
carboplatin B-Chemical 0
AUC O 0
6 O 0
. O 0

Effects O 0
of O 0
acute O 0
steroid B-Chemical 0
administration O 0
on O 0
ventilatory O 0
and O 0
peripheral O 0
muscles O 0
in O 0
rats O 0
. O 0

Occasional O 0
case O 0
reports O 0
have O 0
shown O 0
that O 0
acute O 0
myopathy B-Disease 0
may O 0
occur O 0
in O 0
patients O 0
treated O 0
with O 0
massive O 0
doses O 0
of O 0
corticosteroids B-Chemical 0
. O 0

The O 0
mechanism O 0
of O 0
this O 0
myopathy B-Disease 0
is O 0
poorly O 0
understood O 0
. O 0

Therefore O 0
, O 0
60 O 0
male O 0
rats O 0
were O 0
randomly O 0
assigned O 0
to O 0
receive O 0
daily O 0
injection O 0
of O 0
saline O 0
( O 0
C O 0
) O 0
, O 0
methylprednisolone B-Chemical 0
( O 0
M B-Chemical 0
) O 0
, O 0
or O 0
triamcinolone B-Chemical 0
( O 0
T B-Chemical 0
) O 0
80 O 0
mg O 0
/ O 0
kg O 0
/ O 0
d O 0
for O 0
5 O 0
d O 0
. O 0

Nutritional O 0
intake O 0
, O 0
measured O 0
daily O 0
in O 0
15 O 0
animals O 0
, O 0
showed O 0
a O 0
significant O 0
reduction B-Disease 0
of I-Disease 0
food I-Disease 0
intake I-Disease 0
in O 0
the O 0
steroid B-Chemical 0
- O 0
treated O 0
groups O 0
( O 0
- O 0
50 O 0
and O 0
- O 0
79 O 0
% O 0
in O 0
M B-Chemical 0
and O 0
T B-Chemical 0
, O 0
respectively O 0
) O 0
. O 0

This O 0
was O 0
associated O 0
with O 0
a O 0
similar O 0
loss B-Disease 0
in I-Disease 0
body I-Disease 0
weight I-Disease 0
. O 0

In O 0
the O 0
45 O 0
remaining O 0
animals O 0
, O 0
diaphragm O 0
contractility O 0
and O 0
histopathologic O 0
features O 0
of O 0
several O 0
muscles O 0
were O 0
studied O 0
. O 0

Weights O 0
of O 0
respiratory O 0
and O 0
peripheral O 0
muscles O 0
were O 0
similarly O 0
decreased O 0
after O 0
steroid B-Chemical 0
treatment O 0
. O 0

Maximal O 0
twitches O 0
of O 0
the O 0
diaphragm O 0
were O 0
lower O 0
in O 0
the O 0
C O 0
group O 0
( O 0
653 O 0
+ O 0
/ O 0
- O 0
174 O 0
g O 0
/ O 0
cm O 0
( O 0
2 O 0
) O 0
) O 0
than O 0
in O 0
the O 0
M B-Chemical 0
group O 0
( O 0
837 O 0
+ O 0
/ O 0
- O 0
171 O 0
g O 0
/ O 0
cm O 0
( O 0
2 O 0
) O 0
; O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
and O 0
the O 0
T B-Chemical 0
group O 0
( O 0
765 O 0
+ O 0
/ O 0
- O 0
145 O 0
g O 0
/ O 0
cm O 0
( O 0
2 O 0
) O 0
, O 0
NS O 0
) O 0
. O 0

Half O 0
- O 0
relaxation O 0
time O 0
was O 0
prolonged O 0
in O 0
both O 0
steroid B-Chemical 0
groups O 0
, O 0
and O 0
time O 0
to O 0
peak O 0
tension O 0
was O 0
longer O 0
with O 0
M B-Chemical 0
, O 0
whereas O 0
tetanic B-Disease 0
tensions O 0
were O 0
similar O 0
. O 0

Steroid B-Chemical 0
treatment O 0
also O 0
induced O 0
a O 0
leftward O 0
shift O 0
of O 0
the O 0
force O 0
- O 0
frequency O 0
curve O 0
at O 0
25 O 0
and O 0
50 O 0
Hz O 0
when O 0
compared O 0
with O 0
saline O 0
treatment O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

ATPase O 0
staining O 0
of O 0
the O 0
diaphragm O 0
, O 0
scalenus O 0
medius O 0
, O 0
and O 0
gastrocnemius O 0
showed O 0
type O 0
IIb O 0
fiber O 0
atrophy B-Disease 0
in O 0
the O 0
steroid B-Chemical 0
groups O 0
and O 0
also O 0
diaphragmatic O 0
type O 0
IIa O 0
atrophy B-Disease 0
with O 0
T B-Chemical 0
, O 0
whereas O 0
histologic O 0
examinations O 0
revealed O 0
a O 0
normal O 0
muscular O 0
pattern O 0
with O 0
absence O 0
of O 0
necrosis B-Disease 0
. O 0

Finally O 0
, O 0
a O 0
pair O 0
- O 0
fed O 0
( O 0
PF O 0
) O 0
study O 0
, O 0
performed O 0
in O 0
18 O 0
rats O 0
( O 0
C O 0
, O 0
T B-Chemical 0
, O 0
and O 0
PF O 0
) O 0
, O 0
showed O 0
that O 0
muscle B-Disease 0
atrophy I-Disease 0
was O 0
considerably O 0
less O 0
pronounced O 0
in O 0
PF O 0
animals O 0
than O 0
in O 0
T B-Chemical 0
- O 0
treated O 0
animals O 0
. O 0

We O 0
conclude O 0
that O 0
( O 0
1 O 0
) O 0
short O 0
- O 0
term O 0
treatment O 0
with O 0
massive O 0
doses O 0
of O 0
steroids B-Chemical 0
induced O 0
severe O 0
respiratory O 0
and O 0
limb O 0
muscle O 0
wasting O 0
; O 0
( O 0
2 O 0
) O 0
both O 0
types O 0
of O 0
steroids B-Chemical 0
induced O 0
predominantly O 0
type O 0
IIb O 0
atrophy B-Disease 0
, O 0
resulting O 0
in O 0
the O 0
expected O 0
alterations O 0
in O 0
diaphragm O 0
contractile O 0
properties O 0
; O 0
( O 0
3 O 0
) O 0
neither O 0
steroid B-Chemical 0
caused O 0
muscle O 0
necrosis B-Disease 0
; O 0
( O 0
4 O 0
) O 0
type O 0
IIb O 0
atrophy B-Disease 0
was O 0
not O 0
caused O 0
by O 0
acute O 0
nutritional O 0
deprivation O 0
alone O 0
. O 0

Continuous O 0
subcutaneous O 0
administration O 0
of O 0
mesna B-Chemical 0
to O 0
prevent O 0
ifosfamide B-Chemical 0
- O 0
induced O 0
hemorrhagic B-Disease 0
cystitis I-Disease 0
. O 0

Hemorrhagic B-Disease 0
cystitis I-Disease 0
is O 0
a O 0
major O 0
potential O 0
toxicity B-Disease 0
of O 0
ifosfamide B-Chemical 0
that O 0
can O 0
be O 0
prevented O 0
by O 0
administering O 0
mesna B-Chemical 0
along O 0
with O 0
the O 0
cytotoxic O 0
agent O 0
. O 0

Mesna B-Chemical 0
is O 0
generally O 0
administered O 0
by O 0
the O 0
intravenous O 0
route O 0
, O 0
although O 0
experience O 0
with O 0
oral O 0
delivery O 0
of O 0
the O 0
drug O 0
has O 0
increased O 0
. O 0

The O 0
continuous O 0
subcutaneous O 0
administration O 0
of O 0
mesna B-Chemical 0
has O 0
the O 0
advantage O 0
of O 0
not O 0
requiring O 0
intravenous O 0
access O 0
. O 0

In O 0
addition O 0
, O 0
subcutaneous O 0
delivery O 0
of O 0
the O 0
neutralizing O 0
agent O 0
will O 0
not O 0
be O 0
associated O 0
with O 0
the O 0
risk O 0
of O 0
inadequate O 0
urinary O 0
mesna B-Chemical 0
concentrations O 0
, O 0
such O 0
as O 0
in O 0
a O 0
patient O 0
taking O 0
oral O 0
mesna B-Chemical 0
who O 0
experiences O 0
severe O 0
ifosfamide B-Chemical 0
- O 0
induced O 0
emesis B-Disease 0
and O 0
is O 0
unable O 0
to O 0
absorb O 0
the O 0
drug O 0
. O 0

Limited O 0
clinical O 0
experience O 0
with O 0
continuous O 0
subcutaneous O 0
mesna B-Chemical 0
administration O 0
suggests O 0
it O 0
is O 0
a O 0
safe O 0
, O 0
practical O 0
, O 0
and O 0
economic O 0
method O 0
of O 0
drug O 0
delivery O 0
that O 0
permits O 0
ifosfamide B-Chemical 0
to O 0
be O 0
administered O 0
successfully O 0
in O 0
the O 0
outpatient O 0
setting O 0
. O 0

Leg B-Disease 0
and I-Disease 0
back I-Disease 0
pain I-Disease 0
after O 0
spinal O 0
anaesthesia O 0
involving O 0
hyperbaric O 0
5 O 0
% O 0
lignocaine B-Chemical 0
. O 0

Fifty O 0
- O 0
four O 0
patients O 0
, O 0
aged O 0
27 O 0
- O 0
90 O 0
years O 0
, O 0
who O 0
were O 0
given O 0
lignocaine B-Chemical 0
5 O 0
% O 0
in O 0
6 O 0
. O 0
8 O 0
% O 0
glucose B-Chemical 0
solution O 0
for O 0
spinal O 0
anaesthesia O 0
were O 0
studied O 0
. O 0

Thirteen O 0
of O 0
these O 0
patients O 0
experienced O 0
pain B-Disease 0
in I-Disease 0
the I-Disease 0
legs I-Disease 0
and I-Disease 0
/ I-Disease 0
or I-Disease 0
back I-Disease 0
after O 0
recovery O 0
from O 0
anaesthesia O 0
. O 0

The O 0
patients O 0
affected O 0
were O 0
younger O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
and O 0
the O 0
site O 0
of O 0
the O 0
dural O 0
puncture O 0
was O 0
higher O 0
( O 0
p O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
than O 0
those O 0
individuals O 0
without O 0
pain B-Disease 0
. O 0

Five O 0
of O 0
the O 0
13 O 0
patients O 0
( O 0
38 O 0
% O 0
) O 0
with O 0
pain B-Disease 0
and O 0
seven O 0
of O 0
the O 0
41 O 0
patients O 0
( O 0
17 O 0
% O 0
) O 0
without O 0
pain B-Disease 0
admitted O 0
to O 0
a O 0
high O 0
alcohol B-Chemical 0
intake O 0
, O 0
which O 0
might O 0
be O 0
a O 0
contributing O 0
factor O 0
. O 0

Leg B-Disease 0
and I-Disease 0
/ I-Disease 0
or I-Disease 0
back I-Disease 0
pain I-Disease 0
is O 0
associated O 0
with O 0
the O 0
intrathecal O 0
use O 0
of O 0
hyperbaric O 0
5 O 0
% O 0
lignocaine B-Chemical 0
. O 0

The O 0
use O 0
of O 0
serum O 0
cholinesterase O 0
in O 0
succinylcholine B-Chemical 0
apnoea B-Disease 0
. O 0

Fifteen O 0
patients O 0
demonstrating O 0
unexpected O 0
prolonged O 0
apnoea B-Disease 0
lasting O 0
several O 0
hours O 0
after O 0
succinylcholine B-Chemical 0
have O 0
been O 0
treated O 0
by O 0
a O 0
new O 0
preparation O 0
of O 0
human O 0
serum O 0
cholinesterase O 0
. O 0

Adequate O 0
spontaneous O 0
respiration O 0
was O 0
re O 0
- O 0
established O 0
in O 0
an O 0
average O 0
period O 0
of O 0
ten O 0
minutes O 0
after O 0
the O 0
injection O 0
. O 0

In O 0
12 O 0
patients O 0
biochemical O 0
genetic O 0
examinations O 0
confirmed O 0
the O 0
presence O 0
of O 0
an O 0
atypical O 0
serum O 0
cholinesterase O 0
. O 0

In O 0
three O 0
patients O 0
none O 0
of O 0
the O 0
usual O 0
variants O 0
were O 0
found O 0
. O 0

It O 0
is O 0
therefore O 0
supposed O 0
that O 0
other O 0
unknown O 0
variants O 0
of O 0
serum O 0
cholinesterase O 0
exist O 0
which O 0
cannot O 0
hydrolyze O 0
succinylcholine B-Chemical 0
. O 0

The O 0
use O 0
of O 0
serum O 0
cholinesterase O 0
in O 0
succinylcholine B-Chemical 0
apnoea B-Disease 0
provided O 0
considerable O 0
relief O 0
to O 0
both O 0
patient O 0
and O 0
anaesthetist O 0
. O 0

Increased O 0
sulfation O 0
and O 0
decreased O 0
7alpha O 0
- O 0
hydroxylation O 0
of O 0
deoxycholic B-Chemical 0
acid I-Chemical 0
in O 0
ethinyl B-Chemical 0
estradiol I-Chemical 0
- O 0
induced O 0
cholestasis B-Disease 0
in O 0
rats O 0
. O 0

Deoxycholic B-Chemical 0
acid I-Chemical 0
conjugation O 0
, O 0
transport O 0
capacity O 0
, O 0
and O 0
metabolism O 0
were O 0
compared O 0
in O 0
control O 0
and O 0
ethinyl B-Chemical 0
estradiol I-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

Control O 0
rats O 0
were O 0
found O 0
to O 0
have O 0
a O 0
lower O 0
capacity O 0
to O 0
transport O 0
deoxycholic B-Chemical 0
acid I-Chemical 0
than O 0
taurodeoxycholic B-Chemical 0
acid I-Chemical 0
, O 0
and O 0
both O 0
were O 0
decreased O 0
by O 0
ethinyl B-Chemical 0
estradiol I-Chemical 0
treatment O 0
. O 0

During O 0
[ O 0
24 O 0
- O 0
14C O 0
] O 0
sodium B-Chemical 0
deoxycholate I-Chemical 0
infusion O 0
, O 0
[ O 0
14C O 0
] O 0
biliary O 0
bile B-Chemical 0
acid I-Chemical 0
secretion O 0
increased O 0
, O 0
but O 0
bile O 0
flow O 0
did O 0
not O 0
change O 0
significantly O 0
in O 0
either O 0
control O 0
or O 0
ethinyl B-Chemical 0
estradiol I-Chemical 0
- O 0
treated O 0
rats O 0
. O 0

Ethinyl B-Chemical 0
estradiol I-Chemical 0
- O 0
treated O 0
animals O 0
excreted O 0
significantly O 0
less O 0
14C O 0
as O 0
taurocholic B-Chemical 0
acid I-Chemical 0
than O 0
did O 0
control O 0
animals O 0
, O 0
consistent O 0
with O 0
an O 0
impairment O 0
of O 0
7alpha O 0
- O 0
hydroxylation O 0
of O 0
taurodeoxycholic B-Chemical 0
acid I-Chemical 0
. O 0

Ethinyl B-Chemical 0
estradiol I-Chemical 0
treatment O 0
did O 0
not O 0
impair O 0
conjugation O 0
of O 0
deoxycholic B-Chemical 0
acid I-Chemical 0
, O 0
but O 0
did O 0
result O 0
in O 0
an O 0
increase O 0
in O 0
sulfation O 0
of O 0
taurodeoxycholic B-Chemical 0
acid I-Chemical 0
from O 0
1 O 0
. O 0
5 O 0
% O 0
in O 0
controls O 0
to O 0
nearly O 0
4 O 0
. O 0
0 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

These O 0
results O 0
are O 0
consistent O 0
with O 0
the O 0
hypothesis O 0
that O 0
the O 0
rat O 0
has O 0
a O 0
poorer O 0
tolerance O 0
for O 0
deoxycholic B-Chemical 0
acid I-Chemical 0
than O 0
do O 0
certain O 0
other O 0
species O 0
. O 0

Furthermore O 0
, O 0
the O 0
rat O 0
converts O 0
deoxycholic B-Chemical 0
acid I-Chemical 0
, O 0
a O 0
poor O 0
choleretic O 0
, O 0
to O 0
taurocholic B-Chemical 0
acid I-Chemical 0
, O 0
a O 0
good O 0
choleretic O 0
. O 0

When O 0
this O 0
conversion O 0
is O 0
impaired O 0
with O 0
ethinyl B-Chemical 0
estradiol I-Chemical 0
treatment O 0
, O 0
sulfation O 0
may O 0
be O 0
an O 0
important O 0
alternate O 0
pathway O 0
for O 0
excretion O 0
of O 0
this O 0
potentially O 0
harmful O 0
bile B-Chemical 0
acid I-Chemical 0
. O 0

Influence O 0
of O 0
diet O 0
free O 0
of O 0
NAD B-Chemical 0
- O 0
precursors O 0
on O 0
acetaminophen B-Chemical 0
hepatotoxicity B-Disease 0
in O 0
mice O 0
. O 0

Recently O 0
, O 0
we O 0
demonstrated O 0
the O 0
hepatoprotective O 0
effects O 0
of O 0
nicotinic B-Chemical 0
acid I-Chemical 0
amide I-Chemical 0
, O 0
a O 0
selective O 0
inhibitor O 0
of O 0
poly B-Chemical 0
( I-Chemical 0
ADP I-Chemical 0
- I-Chemical 0
ribose I-Chemical 0
) I-Chemical 0
polymerase O 0
( O 0
PARP O 0
; O 0
EC O 0
2 O 0
. O 0
4 O 0
. O 0
2 O 0
. O 0
30 O 0
) O 0
on O 0
mice O 0
suffering O 0
from O 0
acetaminophen B-Chemical 0
( O 0
AAP B-Chemical 0
) O 0
- O 0
hepatitis B-Disease 0
, O 0
suggesting O 0
that O 0
the O 0
AAP B-Chemical 0
- O 0
induced O 0
liver B-Disease 0
injury I-Disease 0
involves O 0
a O 0
step O 0
which O 0
depends O 0
on O 0
adenoribosylation 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
a O 0
diet O 0
free O 0
of O 0
precursors O 0
of O 0
NAD B-Chemical 0
, O 0
the O 0
substrate O 0
on O 0
which O 0
PARP O 0
acts O 0
, O 0
in O 0
female O 0
NMRI O 0
mice O 0
with O 0
AAP B-Chemical 0
hepatitis B-Disease 0
and O 0
evaluates O 0
the O 0
influence O 0
of O 0
simultaneous O 0
ethanol B-Chemical 0
consumption O 0
in O 0
these O 0
animals O 0
. O 0

Liver B-Disease 0
injuries I-Disease 0
were O 0
quantified O 0
as O 0
serum O 0
activities O 0
of O 0
glutamate B-Chemical 0
- O 0
oxaloacetate B-Chemical 0
transaminase O 0
( O 0
GOT O 0
) O 0
and O 0
glutamate B-Chemical 0
- O 0
pyruvate B-Chemical 0
transaminase O 0
( O 0
GPT O 0
) O 0
. O 0

While O 0
AAP B-Chemical 0
caused O 0
a O 0
117 O 0
- O 0
fold O 0
elevation O 0
of O 0
serum O 0
transaminase O 0
activities O 0
in O 0
mice O 0
kept O 0
on O 0
a O 0
standard O 0
laboratory O 0
diet O 0
, O 0
which O 0
was O 0
significantly O 0
exacerbated O 0
by O 0
ethanol B-Chemical 0
and O 0
inhibited O 0
by O 0
nicotinic B-Chemical 0
acid I-Chemical 0
amide I-Chemical 0
( O 0
NAA B-Chemical 0
) O 0
, O 0
adverse O 0
effects O 0
were O 0
noted O 0
in O 0
animals O 0
fed O 0
a O 0
diet O 0
free O 0
of O 0
precursors O 0
of O 0
NAD B-Chemical 0
. O 0

In O 0
these O 0
animals O 0
, O 0
only O 0
minor O 0
increases O 0
of O 0
serum O 0
transaminase O 0
activities O 0
were O 0
measured O 0
in O 0
the O 0
presence O 0
of O 0
AAP B-Chemical 0
, O 0
and O 0
unlike O 0
the O 0
exacerbation O 0
caused O 0
by O 0
ethanol B-Chemical 0
in O 0
mice O 0
on O 0
a O 0
standard O 0
diet O 0
, O 0
the O 0
liver B-Disease 0
damage I-Disease 0
was O 0
inhibited O 0
by O 0
50 O 0
% O 0
by O 0
ethanol B-Chemical 0
. O 0

A O 0
further O 0
64 O 0
% O 0
reduction O 0
of O 0
hepatitis B-Disease 0
was O 0
observed O 0
, O 0
when O 0
NAA B-Chemical 0
was O 0
given O 0
to O 0
ethanol B-Chemical 0
/ O 0
AAP B-Chemical 0
- O 0
mice O 0
. O 0

Our O 0
results O 0
provide O 0
evidence O 0
that O 0
the O 0
AAP B-Chemical 0
- O 0
induced O 0
hepatitis B-Disease 0
and O 0
its O 0
exacerbation O 0
by O 0
ethanol B-Chemical 0
can O 0
either O 0
be O 0
reduced O 0
by O 0
end O 0
- O 0
product O 0
inhibition O 0
of O 0
PARP O 0
by O 0
NAA B-Chemical 0
or O 0
by O 0
dietary O 0
depletion O 0
of O 0
the O 0
enzyme O 0
' O 0
s O 0
substrate O 0
NAD B-Chemical 0
. O 0

We O 0
see O 0
the O 0
main O 0
application O 0
of O 0
NAA B-Chemical 0
as O 0
for O 0
the O 0
combinational O 0
use O 0
in O 0
pharmaceutical O 0
preparations O 0
of O 0
acetaminophen B-Chemical 0
in O 0
order O 0
to O 0
avoid O 0
hepatic B-Disease 0
damage I-Disease 0
in O 0
patients O 0
treated O 0
with O 0
this O 0
widely O 0
used O 0
analgesic O 0
. O 0

Nightmares O 0
and O 0
hallucinations B-Disease 0
after O 0
long O 0
- O 0
term O 0
intake O 0
of O 0
tramadol B-Chemical 0
combined O 0
with O 0
antidepressants O 0
. O 0

Tramadol B-Chemical 0
is O 0
a O 0
weak O 0
opioid O 0
with O 0
effects O 0
on O 0
adrenergic O 0
and O 0
serotonergic O 0
neurotransmission O 0
that O 0
is O 0
used O 0
to O 0
treat O 0
cancer B-Disease 0
pain B-Disease 0
and O 0
chronic O 0
non O 0
malignant O 0
pain B-Disease 0
. O 0

This O 0
drug O 0
was O 0
initiated O 0
in O 0
association O 0
with O 0
paroxetine B-Chemical 0
and O 0
dosulepine B-Chemical 0
hydrochloride I-Chemical 0
in O 0
a O 0
tetraparetic B-Disease 0
patient O 0
with O 0
chronic B-Disease 0
pain I-Disease 0
. O 0

Fifty O 0
- O 0
six O 0
days O 0
after O 0
initiation O 0
of O 0
the O 0
treatment O 0
the O 0
patient O 0
presented O 0
hallucinations B-Disease 0
that O 0
only O 0
stopped O 0
after O 0
the O 0
withdrawal O 0
of O 0
psycho O 0
- O 0
active O 0
drugs O 0
and O 0
tramadol B-Chemical 0
. O 0

The O 0
case O 0
report O 0
questions O 0
the O 0
long O 0
term O 0
use O 0
of O 0
pain B-Disease 0
killers O 0
combined O 0
with O 0
psycho O 0
- O 0
active O 0
drugs O 0
in O 0
chronic O 0
non O 0
malignant O 0
pain B-Disease 0
, O 0
especially O 0
if O 0
pain B-Disease 0
is O 0
under O 0
control O 0
. O 0

Effect O 0
of O 0
calcium B-Chemical 0
chloride I-Chemical 0
and O 0
4 B-Chemical 0
- I-Chemical 0
aminopyridine I-Chemical 0
therapy O 0
on O 0
desipramine B-Chemical 0
toxicity B-Disease 0
in O 0
rats O 0
. O 0

BACKGROUND O 0
: O 0
Hypotension B-Disease 0
is O 0
a O 0
major O 0
contributor O 0
to O 0
mortality O 0
in O 0
tricyclic O 0
antidepressant O 0
overdose B-Disease 0
. O 0

Recent O 0
data O 0
suggest O 0
that O 0
tricyclic O 0
antidepressants O 0
inhibit O 0
calcium B-Chemical 0
influx O 0
in O 0
some O 0
tissues O 0
. O 0

This O 0
study O 0
addressed O 0
the O 0
potential O 0
role O 0
of O 0
calcium B-Chemical 0
channel O 0
blockade O 0
in O 0
tricyclic O 0
antidepressant O 0
- O 0
induced O 0
hypotension B-Disease 0
. O 0

METHODS O 0
: O 0
Two O 0
interventions O 0
were O 0
studied O 0
that O 0
have O 0
been O 0
shown O 0
previously O 0
to O 0
improve O 0
blood O 0
pressure O 0
with O 0
calcium B-Chemical 0
channel O 0
blocker O 0
overdose B-Disease 0
. O 0

CaCl2 B-Chemical 0
and O 0
4 B-Chemical 0
- I-Chemical 0
aminopyridine I-Chemical 0
. O 0

Anesthetized O 0
rats O 0
received O 0
the O 0
tricyclic O 0
antidepressant O 0
desipramine B-Chemical 0
IP O 0
to O 0
produce O 0
hypotension B-Disease 0
, O 0
QRS O 0
prolongation O 0
, O 0
and O 0
bradycardia B-Disease 0
. O 0

Fifteen O 0
min O 0
later O 0
, O 0
animals O 0
received O 0
CaCl2 B-Chemical 0
, O 0
NaHCO3 B-Chemical 0
, O 0
or O 0
saline O 0
. O 0

In O 0
a O 0
second O 0
experiment O 0
, O 0
rats O 0
received O 0
tricyclic O 0
antidepressant O 0
desipramine B-Chemical 0
IP O 0
followed O 0
in O 0
15 O 0
min O 0
by O 0
4 B-Chemical 0
- I-Chemical 0
aminopyridine I-Chemical 0
or O 0
saline O 0
. O 0

RESULTS O 0
: O 0
NaHCO3 B-Chemical 0
briefly O 0
( O 0
5 O 0
min O 0
) O 0
reversed O 0
hypotension B-Disease 0
and O 0
QRS O 0
prolongation O 0
. O 0

CaCl2 B-Chemical 0
and O 0
4 B-Chemical 0
- I-Chemical 0
aminopyridine I-Chemical 0
failed O 0
to O 0
improve O 0
blood O 0
pressure O 0
. O 0

The O 0
incidence O 0
of O 0
ventricular B-Disease 0
arrhythmias I-Disease 0
( O 0
p O 0
= O 0
0 O 0
. O 0
004 O 0
) O 0
and O 0
seizures B-Disease 0
( O 0
p O 0
= O 0
0 O 0
. O 0
03 O 0
) O 0
in O 0
the O 0
CaCl2 B-Chemical 0
group O 0
was O 0
higher O 0
than O 0
the O 0
other O 0
groups O 0
. O 0

CONCLUSION O 0
: O 0
The O 0
administration O 0
of O 0
CaCl2 B-Chemical 0
or O 0
4 B-Chemical 0
- I-Chemical 0
aminopyridine I-Chemical 0
did O 0
not O 0
reverse O 0
tricyclic O 0
antidepressant O 0
- O 0
induced O 0
hypotension B-Disease 0
in O 0
rats O 0
. O 0

CaCl2 B-Chemical 0
therapy O 0
may O 0
possibly O 0
worsen O 0
both O 0
cardiovascular B-Disease 0
and I-Disease 0
central I-Disease 0
nervous I-Disease 0
system I-Disease 0
toxicity I-Disease 0
. O 0

These O 0
findings O 0
do O 0
not O 0
support O 0
a O 0
role O 0
for O 0
calcium B-Chemical 0
channel O 0
inhibition O 0
in O 0
the O 0
pathogenesis O 0
of O 0
tricyclic O 0
antidepressant O 0
- O 0
induced O 0
hypotension B-Disease 0
. O 0

Valsartan B-Chemical 0
, O 0
a O 0
new O 0
angiotensin B-Chemical 0
II I-Chemical 0
antagonist O 0
for O 0
the O 0
treatment O 0
of O 0
essential O 0
hypertension B-Disease 0
: O 0
a O 0
comparative O 0
study O 0
of O 0
the O 0
efficacy O 0
and O 0
safety O 0
against O 0
amlodipine B-Chemical 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
compare O 0
the O 0
antihypertensive O 0
efficacy O 0
of O 0
a O 0
new O 0
angiotensin B-Chemical 0
II I-Chemical 0
antagonist O 0
, O 0
valsartan B-Chemical 0
, O 0
with O 0
a O 0
reference O 0
therapy O 0
, O 0
amlodipine B-Chemical 0
. O 0

METHODS O 0
: O 0
One O 0
hundred O 0
sixty O 0
- O 0
eight O 0
adult O 0
outpatients O 0
with O 0
mild O 0
to O 0
moderate O 0
hypertension B-Disease 0
were O 0
randomly O 0
allocated O 0
in O 0
double O 0
- O 0
blind O 0
fashion O 0
and O 0
equal O 0
number O 0
to O 0
receive O 0
80 O 0
mg O 0
valsartan B-Chemical 0
or O 0
5 O 0
mg O 0
amlodipine B-Chemical 0
for O 0
12 O 0
weeks O 0
. O 0

After O 0
8 O 0
weeks O 0
of O 0
therapy O 0
, O 0
in O 0
patients O 0
whose O 0
blood O 0
pressure O 0
remained O 0
uncontrolled O 0
, O 0
5 O 0
mg O 0
amlodipine B-Chemical 0
was O 0
added O 0
to O 0
the O 0
initial O 0
therapy O 0
. O 0

Patients O 0
were O 0
assessed O 0
at O 0
4 O 0
, O 0
8 O 0
, O 0
and O 0
12 O 0
weeks O 0
. O 0

The O 0
primary O 0
efficacy O 0
variable O 0
was O 0
change O 0
from O 0
baseline O 0
in O 0
mean O 0
sitting O 0
diastolic O 0
blood O 0
pressure O 0
at O 0
8 O 0
weeks O 0
. O 0

Secondary O 0
variables O 0
included O 0
change O 0
in O 0
sitting O 0
systolic O 0
blood O 0
pressure O 0
and O 0
responder O 0
rates O 0
. O 0

RESULTS O 0
: O 0
Both O 0
valsartan B-Chemical 0
and O 0
amlodipine B-Chemical 0
were O 0
effective O 0
at O 0
lowering O 0
blood O 0
pressure O 0
at O 0
4 O 0
, O 0
8 O 0
, O 0
and O 0
12 O 0
weeks O 0
. O 0

Similar O 0
decreases O 0
were O 0
observed O 0
in O 0
both O 0
groups O 0
, O 0
with O 0
no O 0
statistically O 0
significant O 0
differences O 0
between O 0
the O 0
groups O 0
for O 0
any O 0
variable O 0
analyzed O 0
. O 0

For O 0
the O 0
primary O 0
variable O 0
the O 0
difference O 0
was O 0
0 O 0
. O 0
5 O 0
mm O 0
Hg O 0
in O 0
favor O 0
of O 0
valsartan B-Chemical 0
( O 0
p O 0
= O 0
0 O 0
. O 0
68 O 0
; O 0
95 O 0
% O 0
confidence O 0
interval O 0
, O 0
- O 0
2 O 0
. O 0
7 O 0
to O 0
1 O 0
. O 0
7 O 0
) O 0
. O 0

Responder O 0
rates O 0
at O 0
8 O 0
weeks O 0
were O 0
66 O 0
. O 0
7 O 0
% O 0
for O 0
valsartan B-Chemical 0
and O 0
60 O 0
. O 0
2 O 0
% O 0
for O 0
amlodipine B-Chemical 0
( O 0
p O 0
= O 0
0 O 0
. O 0
39 O 0
) O 0
. O 0

Both O 0
treatments O 0
were O 0
well O 0
tolerated O 0
. O 0

The O 0
incidence O 0
of O 0
drug O 0
- O 0
related O 0
dependent O 0
edema B-Disease 0
was O 0
somewhat O 0
higher O 0
in O 0
the O 0
amlodipine B-Chemical 0
group O 0
, O 0
particularly O 0
at O 0
a O 0
dose O 0
of O 0
10 O 0
mg O 0
per O 0
day O 0
( O 0
2 O 0
. O 0
4 O 0
% O 0
for O 0
80 O 0
mg O 0
valsartan B-Chemical 0
; O 0
3 O 0
. O 0
6 O 0
% O 0
for O 0
5 O 0
mg O 0
amlodipine B-Chemical 0
; O 0
0 O 0
% O 0
for O 0
valsartan B-Chemical 0
plus O 0
5 O 0
mg O 0
amlodipine B-Chemical 0
; O 0
14 O 0
. O 0
3 O 0
% O 0
for O 0
10 O 0
mg O 0
amlodipine B-Chemical 0
) O 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
data O 0
show O 0
that O 0
valsartan B-Chemical 0
is O 0
at O 0
least O 0
as O 0
effective O 0
as O 0
amlodipine B-Chemical 0
in O 0
the O 0
treatment O 0
of O 0
mild O 0
to O 0
moderate O 0
hypertension B-Disease 0
. O 0

The O 0
results O 0
also O 0
show O 0
valsartan B-Chemical 0
to O 0
be O 0
well O 0
tolerated O 0
and O 0
suggest O 0
that O 0
it O 0
is O 0
not O 0
associated O 0
with O 0
side O 0
effects O 0
characteristic O 0
of O 0
this O 0
comparator O 0
class O 0
, O 0
dihydropyridine B-Chemical 0
calcium B-Chemical 0
antagonists O 0
. O 0

A O 0
measure O 0
of O 0
pupillary B-Disease 0
oscillation I-Disease 0
as O 0
a O 0
marker O 0
of O 0
cocaine B-Chemical 0
- O 0
induced O 0
paranoia B-Disease 0
. O 0

Cocaine B-Chemical 0
- O 0
induced O 0
paranoia B-Disease 0
( O 0
CIP B-Disease 0
) O 0
remains O 0
an O 0
important O 0
drug O 0
- O 0
induced O 0
model O 0
of O 0
idiopathic O 0
paranoia B-Disease 0
for O 0
which O 0
no O 0
psychophysiologic O 0
marker O 0
has O 0
yet O 0
emerged O 0
. O 0

Measures O 0
of O 0
pupillary B-Disease 0
oscillation I-Disease 0
were O 0
able O 0
to O 0
significantly O 0
distinguish O 0
a O 0
group O 0
of O 0
abstinent O 0
crack B-Chemical 0
cocaine I-Chemical 0
abusers O 0
endorsing O 0
past O 0
CIP B-Disease 0
( O 0
n O 0
= O 0
32 O 0
) O 0
from O 0
another O 0
group O 0
of O 0
crack B-Chemical 0
addicts O 0
who O 0
denied O 0
past O 0
CIP B-Disease 0
( O 0
n O 0
= O 0
29 O 0
) O 0
. O 0

Serotonin B-Disease 0
syndrome I-Disease 0
from O 0
venlafaxine B-Chemical 0
- O 0
tranylcypromine B-Chemical 0
interaction O 0
. O 0

Excessive O 0
stimulation O 0
of O 0
serotonin B-Chemical 0
5HT1A O 0
receptors O 0
causes O 0
a O 0
syndrome O 0
of O 0
serotonin B-Chemical 0
excess O 0
that O 0
consists O 0
of O 0
shivering O 0
, O 0
muscle B-Disease 0
rigidity I-Disease 0
, O 0
salivation B-Disease 0
, O 0
confusion B-Disease 0
, O 0
agitation B-Disease 0
and O 0
hyperthermia B-Disease 0
. O 0

The O 0
most O 0
common O 0
cause O 0
of O 0
this O 0
syndrome O 0
is O 0
an O 0
interaction O 0
between O 0
a O 0
monoamine O 0
oxidase O 0
inhibitor O 0
( O 0
MAOI O 0
) O 0
and O 0
a O 0
specific O 0
serotonin B-Chemical 0
reuptake O 0
inhibitor O 0
. O 0

Venlafaxine B-Chemical 0
is O 0
a O 0
new O 0
antidepressant O 0
agent O 0
that O 0
inhibits O 0
the O 0
reuptake O 0
of O 0
serotonin B-Chemical 0
and O 0
norepinephrine B-Chemical 0
. O 0

We O 0
report O 0
a O 0
venlafaxine B-Chemical 0
- O 0
MAOI O 0
interaction O 0
that O 0
resulted O 0
in O 0
the O 0
serotonin B-Disease 0
syndrome I-Disease 0
in O 0
a O 0
23 O 0
- O 0
y O 0
- O 0
old O 0
male O 0
who O 0
was O 0
taking O 0
tranylcypromine B-Chemical 0
for O 0
depression B-Disease 0
. O 0

He O 0
had O 0
been O 0
well O 0
until O 0
the O 0
morning O 0
of O 0
presentation O 0
when O 0
he O 0
took O 0
1 O 0
/ O 0
2 O 0
tab O 0
of O 0
venlafaxine B-Chemical 0
. O 0

Within O 0
2 O 0
h O 0
he O 0
became O 0
confused O 0
with O 0
jerking O 0
movements O 0
of O 0
his O 0
extremities O 0
, O 0
tremors B-Disease 0
and O 0
rigidity B-Disease 0
. O 0

He O 0
was O 0
brought O 0
directly O 0
to O 0
a O 0
hospital O 0
where O 0
he O 0
was O 0
found O 0
to O 0
be O 0
agitated O 0
and O 0
confused O 0
with O 0
shivering O 0
, O 0
myoclonic B-Disease 0
jerks I-Disease 0
, O 0
rigidity B-Disease 0
, O 0
salivation B-Disease 0
and O 0
diaphoresis O 0
. O 0

His O 0
pupils O 0
were O 0
7 O 0
mm O 0
and O 0
sluggishly O 0
reactive O 0
to O 0
light O 0
. O 0

Vital O 0
signs O 0
were O 0
: O 0
blood O 0
pressure O 0
120 O 0
/ O 0
67 O 0
mm O 0
Hg O 0
, O 0
heart O 0
rate O 0
127 O 0
/ O 0
min O 0
, O 0
respiratory O 0
rate O 0
28 O 0
/ O 0
min O 0
, O 0
and O 0
temperature O 0
97 O 0
F O 0
. O 0

After O 0
180 O 0
mg O 0
of O 0
diazepam B-Chemical 0
i O 0
. O 0
v O 0
. O 0
he O 0
remained O 0
tremulous O 0
with O 0
muscle B-Disease 0
rigidity I-Disease 0
and O 0
clenched O 0
jaws O 0
. O 0

He O 0
was O 0
intubated O 0
for O 0
airway O 0
protection O 0
and O 0
because O 0
of O 0
hypoventilation B-Disease 0
, O 0
and O 0
was O 0
paralyzed B-Disease 0
to O 0
control O 0
muscle B-Disease 0
rigidity I-Disease 0
. O 0

His O 0
subsequent O 0
course O 0
was O 0
remarkable O 0
for O 0
non O 0
- O 0
immune O 0
thrombocytopenia B-Disease 0
which O 0
resolved O 0
. O 0

The O 0
patient O 0
' O 0
s O 0
maximal O 0
temperature O 0
was O 0
101 O 0
. O 0
2 O 0
F O 0
and O 0
his O 0
CPK O 0
remained O 0
< O 0
500 O 0
units O 0
/ O 0
L O 0
with O 0
no O 0
other O 0
evidence O 0
of O 0
rhabdomyolysis B-Disease 0
. O 0

His O 0
mental O 0
status O 0
normalized O 0
and O 0
he O 0
was O 0
transferred O 0
to O 0
a O 0
psychiatry O 0
ward O 0
. O 0

This O 0
patient O 0
survived O 0
without O 0
sequelae O 0
due O 0
to O 0
the O 0
aggressive O 0
sedation O 0
and O 0
neuromuscular O 0
paralysis B-Disease 0
. O 0

Cyclophosphamide B-Chemical 0
associated O 0
bladder B-Disease 0
cancer I-Disease 0
- O 0
- O 0
a O 0
highly O 0
aggressive O 0
disease O 0
: O 0
analysis O 0
of O 0
12 O 0
cases O 0
. O 0

PURPOSE O 0
: O 0
We O 0
gained O 0
knowledge O 0
of O 0
the O 0
etiology O 0
, O 0
treatment O 0
and O 0
prevention O 0
of O 0
cyclophosphamide B-Chemical 0
associated O 0
urothelial B-Disease 0
cancer I-Disease 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
The O 0
medical O 0
records O 0
of O 0
6 O 0
men O 0
and O 0
6 O 0
women O 0
( O 0
mean O 0
age O 0
55 O 0
years O 0
) O 0
with O 0
cyclophosphamide B-Chemical 0
associated O 0
bladder B-Disease 0
cancer I-Disease 0
were O 0
reviewed O 0
. O 0

RESULTS O 0
: O 0
All O 0
tumors B-Disease 0
were O 0
grade O 0
3 O 0
or O 0
4 O 0
transitional O 0
cell O 0
carcinoma B-Disease 0
. O 0

Of O 0
the O 0
5 O 0
patients O 0
initially O 0
treated O 0
with O 0
endoscopic O 0
resection O 0
alone O 0
only O 0
1 O 0
is O 0
alive O 0
without O 0
disease O 0
. O 0

Of O 0
the O 0
6 O 0
patients O 0
who O 0
underwent O 0
early O 0
cystectomy O 0
4 O 0
were O 0
alive O 0
at O 0
24 O 0
to O 0
111 O 0
months O 0
. O 0

The O 0
remaining O 0
patient O 0
with O 0
extensive O 0
cancer B-Disease 0
underwent O 0
partial O 0
cystectomy O 0
for O 0
palliation O 0
and O 0
died O 0
3 O 0
months O 0
later O 0
. O 0

CONCLUSIONS O 0
: O 0
Cyclophosphamide B-Chemical 0
associated O 0
bladder B-Disease 0
tumor I-Disease 0
is O 0
an O 0
aggressive O 0
disease O 0
. O 0

However O 0
, O 0
long O 0
- O 0
term O 0
survival O 0
is O 0
possible O 0
when O 0
radical O 0
cystectomy O 0
is O 0
performed O 0
for O 0
bladder B-Disease 0
tumors I-Disease 0
with O 0
any O 0
sign O 0
of O 0
invasion O 0
and O 0
for O 0
recurrent O 0
high O 0
grade O 0
disease O 0
, O 0
even O 0
when O 0
noninvasive O 0
. O 0

A O 0
phase O 0
I O 0
clinical O 0
study O 0
of O 0
the O 0
antipurine B-Chemical 0
antifolate O 0
lometrexol B-Chemical 0
( O 0
DDATHF B-Chemical 0
) O 0
given O 0
with O 0
oral O 0
folic B-Chemical 0
acid I-Chemical 0
. O 0

Lometrexol B-Chemical 0
is O 0
an O 0
antifolate O 0
which O 0
inhibits O 0
glycinamide B-Chemical 0
ribonucleotide I-Chemical 0
formyltransferase O 0
( O 0
GARFT O 0
) O 0
, O 0
an O 0
enzyme O 0
essential O 0
for O 0
de O 0
novo O 0
purine B-Chemical 0
synthesis O 0
. O 0

Extensive O 0
experimental O 0
and O 0
limited O 0
clinical O 0
data O 0
have O 0
shown O 0
that O 0
lometrexol B-Chemical 0
has O 0
activity O 0
against O 0
tumours B-Disease 0
which O 0
are O 0
refractory O 0
to O 0
other O 0
drugs O 0
, O 0
notably O 0
methotrexate B-Chemical 0
. O 0

However O 0
, O 0
the O 0
initial O 0
clinical O 0
development O 0
of O 0
lometrexol B-Chemical 0
was O 0
curtailed O 0
because O 0
of O 0
severe O 0
and O 0
cumulative O 0
antiproliferative O 0
toxicities B-Disease 0
. O 0

Preclinical O 0
murine O 0
studies O 0
demonstrated O 0
that O 0
the O 0
toxicity B-Disease 0
of O 0
lometrexol B-Chemical 0
can O 0
be O 0
prevented O 0
by O 0
low O 0
dose O 0
folic B-Chemical 0
acid I-Chemical 0
administration O 0
, O 0
i O 0
. O 0
e O 0
. O 0
for O 0
7 O 0
days O 0
prior O 0
to O 0
and O 0
7 O 0
days O 0
following O 0
a O 0
single O 0
bolus O 0
dose O 0
. O 0

This O 0
observation O 0
prompted O 0
a O 0
Phase O 0
I O 0
clinical O 0
study O 0
of O 0
lometrexol B-Chemical 0
given O 0
with O 0
folic B-Chemical 0
acid I-Chemical 0
supplementation O 0
which O 0
has O 0
confirmed O 0
that O 0
the O 0
toxicity B-Disease 0
of O 0
lometrexol B-Chemical 0
can O 0
be O 0
markedly O 0
reduced O 0
by O 0
folic B-Chemical 0
acid I-Chemical 0
supplementation O 0
. O 0

Thrombocytopenia B-Disease 0
and O 0
mucositis B-Disease 0
were O 0
the O 0
major O 0
toxicities B-Disease 0
. O 0

There O 0
was O 0
no O 0
clear O 0
relationship O 0
between O 0
clinical O 0
toxicity B-Disease 0
and O 0
the O 0
extent O 0
of O 0
plasma O 0
folate B-Chemical 0
elevation O 0
. O 0

Associated O 0
studies O 0
demonstrated O 0
that O 0
lometrexol B-Chemical 0
plasma O 0
pharmacokinetics O 0
were O 0
not O 0
altered O 0
by O 0
folic B-Chemical 0
acid I-Chemical 0
administration O 0
indicating O 0
that O 0
supplementation O 0
is O 0
unlikely O 0
to O 0
reduce O 0
toxicity B-Disease 0
by O 0
enhancing O 0
lometrexol B-Chemical 0
plasma O 0
clearance O 0
. O 0

The O 0
work O 0
described O 0
in O 0
this O 0
report O 0
has O 0
identified O 0
for O 0
the O 0
first O 0
time O 0
a O 0
clinically O 0
acceptable O 0
schedule O 0
for O 0
the O 0
administration O 0
of O 0
a O 0
GARFT O 0
inhibitor O 0
. O 0

This O 0
information O 0
will O 0
facilitate O 0
the O 0
future O 0
evaluation O 0
of O 0
this O 0
class O 0
of O 0
compounds O 0
in O 0
cancer B-Disease 0
therapy O 0
. O 0

Fatal O 0
excited O 0
delirium B-Disease 0
following O 0
cocaine B-Chemical 0
use O 0
: O 0
epidemiologic O 0
findings O 0
provide O 0
new O 0
evidence O 0
for O 0
mechanisms O 0
of O 0
cocaine B-Chemical 0
toxicity B-Disease 0
. O 0

We O 0
describe O 0
an O 0
outbreak O 0
of O 0
deaths O 0
from O 0
cocaine B-Chemical 0
- O 0
induced O 0
excited O 0
delirium B-Disease 0
( O 0
EDDs B-Disease 0
) O 0
in O 0
Dade O 0
County O 0
, O 0
Florida O 0
between O 0
1979 O 0
and O 0
1990 O 0
. O 0

From O 0
a O 0
registry O 0
of O 0
all O 0
cocaine B-Chemical 0
- O 0
related O 0
deaths O 0
in O 0
Dade O 0
County O 0
, O 0
Florida O 0
, O 0
from O 0
1969 O 0
- O 0
1990 O 0
, O 0
58 O 0
EDDs B-Disease 0
were O 0
compared O 0
with O 0
125 O 0
victims O 0
of O 0
accidental O 0
cocaine B-Chemical 0
overdose B-Disease 0
without O 0
excited O 0
delirium B-Disease 0
. O 0

Compared O 0
with O 0
controls O 0
, O 0
EDDs B-Disease 0
were O 0
more O 0
frequently O 0
black O 0
, O 0
male O 0
, O 0
and O 0
younger O 0
. O 0

They O 0
were O 0
less O 0
likely O 0
to O 0
have O 0
a O 0
low O 0
body O 0
mass O 0
index O 0
, O 0
and O 0
more O 0
likely O 0
to O 0
have O 0
died O 0
in O 0
police O 0
custody O 0
, O 0
to O 0
have O 0
received O 0
medical O 0
treatment O 0
immediately O 0
before O 0
death O 0
, O 0
to O 0
have O 0
survived O 0
for O 0
a O 0
longer O 0
period O 0
, O 0
to O 0
have O 0
developed O 0
hyperthermia B-Disease 0
, O 0
and O 0
to O 0
have O 0
died O 0
in O 0
summer O 0
months O 0
. O 0

EDDs B-Disease 0
had O 0
concentrations O 0
of O 0
cocaine B-Chemical 0
and O 0
benzoylecgonine B-Chemical 0
in O 0
autopsy O 0
blood O 0
that O 0
were O 0
similar O 0
to O 0
those O 0
for O 0
controls O 0
. O 0

The O 0
epidemiologic O 0
findings O 0
are O 0
most O 0
consistent O 0
with O 0
the O 0
hypothesis O 0
that O 0
chronic O 0
cocaine B-Chemical 0
use O 0
disrupts O 0
dopaminergic O 0
function O 0
and O 0
, O 0
when O 0
coupled O 0
with O 0
recent O 0
cocaine B-Chemical 0
use O 0
, O 0
may O 0
precipitate O 0
agitation B-Disease 0
, O 0
delirium B-Disease 0
, O 0
aberrant O 0
thermoregulation O 0
, O 0
rhabdomyolysis B-Disease 0
, O 0
and O 0
sudden B-Disease 0
death I-Disease 0
. O 0

Pemoline B-Chemical 0
induced O 0
acute O 0
choreoathetosis B-Disease 0
: 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

BACKGROUND O 0
: O 0
Pemoline B-Chemical 0
is O 0
an O 0
oxazolidine B-Chemical 0
derivative O 0
that O 0
is O 0
structurally O 0
different O 0
from O 0
amphetamines B-Chemical 0
and O 0
used O 0
in O 0
the O 0
treatment O 0
of O 0
attention B-Disease 0
deficit I-Disease 0
disorder I-Disease 0
. O 0

Pemoline B-Chemical 0
has O 0
not O 0
been O 0
commonly O 0
associated O 0
in O 0
the O 0
literature O 0
as O 0
a O 0
cause O 0
of O 0
acute O 0
movement B-Disease 0
disorders I-Disease 0
. O 0

The O 0
following O 0
case O 0
describes O 0
two O 0
children O 0
acutely O 0
poisoned O 0
with O 0
pemoline B-Chemical 0
who O 0
experienced O 0
profound O 0
choreoathetosis B-Disease 0
. O 0

CASE O 0
REPORT O 0
: O 0
Two O 0
, O 0
3 O 0
- O 0
year O 0
- O 0
old O 0
male O 0
, O 0
identical O 0
twin O 0
siblings O 0
presented O 0
to O 0
the O 0
emergency O 0
department O 0
after O 0
found O 0
playing O 0
with O 0
a O 0
an O 0
empty O 0
bottle O 0
of O 0
pemoline B-Chemical 0
originally O 0
containing O 0
59 O 0
tablets O 0
. O 0

The O 0
children O 0
had O 0
a O 0
medical O 0
history O 0
significant O 0
for O 0
attention B-Disease 0
deficit I-Disease 0
disorder I-Disease 0
previously O 0
treated O 0
with O 0
methylphenidate B-Chemical 0
without O 0
success O 0
. O 0

This O 0
was O 0
their O 0
first O 0
day O 0
of O 0
pemoline B-Chemical 0
therapy O 0
. O 0

The O 0
choreoathetoid B-Disease 0
movements O 0
began O 0
45 O 0
min O 0
to O 0
1 O 0
h O 0
after O 0
ingestion O 0
. O 0

The O 0
children O 0
gave O 0
no O 0
history O 0
of O 0
prior O 0
movement B-Disease 0
disorders I-Disease 0
and O 0
there O 0
was O 0
no O 0
family O 0
history O 0
of O 0
movement B-Disease 0
disorders I-Disease 0
. O 0

The O 0
children O 0
received O 0
gastrointestinal O 0
decontamination O 0
and O 0
high O 0
doses O 0
of O 0
intravenous O 0
benzodiazepines B-Chemical 0
in O 0
an O 0
attempt O 0
to O 0
control O 0
the O 0
choreoathetoid B-Disease 0
movements O 0
. O 0

Despite O 0
treatment O 0
, O 0
the O 0
children O 0
continued O 0
to O 0
have O 0
choreoathetosis B-Disease 0
for O 0
approximately O 0
24 O 0
hours O 0
. O 0

Forty O 0
- O 0
eight O 0
hours O 0
after O 0
admission O 0
, O 0
the O 0
children O 0
appeared O 0
to O 0
be O 0
at O 0
their O 0
baseline O 0
and O 0
were O 0
discharged O 0
home O 0
. O 0

CONCLUSION O 0
: O 0
Pemoline B-Chemical 0
associated O 0
movement B-Disease 0
disorder I-Disease 0
has O 0
been O 0
rarely O 0
reported O 0
in O 0
the O 0
acute O 0
toxicology O 0
literature O 0
. O 0

The O 0
possibility O 0
of O 0
choreoathetoid B-Disease 0
movements O 0
should O 0
be O 0
considered O 0
in O 0
patients O 0
presenting O 0
after O 0
pemoline B-Chemical 0
overdose B-Disease 0
. O 0

Effect O 0
of O 0
myopic O 0
excimer O 0
laser O 0
photorefractive O 0
keratectomy O 0
on O 0
the O 0
electrophysiologic O 0
function O 0
of O 0
the O 0
retina O 0
and O 0
optic O 0
nerve O 0
. O 0

PURPOSE O 0
: O 0
To O 0
assess O 0
by O 0
electrophysiologic O 0
testing O 0
the O 0
effect O 0
of O 0
photorefractive O 0
keratectomy O 0
( O 0
PRK O 0
) O 0
on O 0
the O 0
retina O 0
and O 0
optic O 0
nerve O 0
. O 0

SETTING O 0
: O 0
Eye O 0
Clinic O 0
, O 0
S O 0
. O 0

Salvatore O 0
Hospital O 0
, O 0
L O 0
' O 0
Aquila O 0
University O 0
, O 0
Italy O 0
. O 0

METHODS O 0
: O 0
Standard O 0
pattern O 0
electroretinograms O 0
( O 0
P O 0
- O 0
ERGs O 0
) O 0
and O 0
standard O 0
pattern O 0
visual O 0
evoked O 0
potentials O 0
( O 0
P O 0
- O 0
VEPs O 0
) O 0
were O 0
done O 0
in O 0
25 O 0
eyes O 0
of O 0
25 O 0
patients O 0
who O 0
had O 0
myopic O 0
PRK O 0
for O 0
an O 0
attempted O 0
correction O 0
between O 0
5 O 0
. O 0
00 O 0
and O 0
15 O 0
. O 0
00 O 0
diopters O 0
( O 0
D O 0
) O 0
( O 0
mean O 0
8 O 0
. O 0
00 O 0
D O 0
) O 0
. O 0

Testing O 0
was O 0
done O 0
preoperatively O 0
and O 0
3 O 0
, O 0
6 O 0
, O 0
12 O 0
, O 0
and O 0
18 O 0
months O 0
postoperatively O 0
. O 0

The O 0
contralateral O 0
eyes O 0
served O 0
as O 0
controls O 0
. O 0

During O 0
the O 0
follow O 0
- O 0
up O 0
, O 0
3 O 0
patients O 0
( O 0
12 O 0
% O 0
) O 0
developed O 0
steroid B-Chemical 0
- O 0
induced O 0
elevated B-Disease 0
intraocular I-Disease 0
pressure I-Disease 0
( O 0
IOP O 0
) O 0
that O 0
resolved O 0
after O 0
corticosteroid B-Chemical 0
therapy O 0
was O 0
discontinued O 0
. O 0

RESULTS O 0
: O 0
No O 0
statistically O 0
significant O 0
differences O 0
were O 0
seen O 0
between O 0
treated O 0
and O 0
control O 0
eyes O 0
nor O 0
between O 0
treated O 0
eyes O 0
preoperatively O 0
and O 0
postoperatively O 0
. O 0

CONCLUSION O 0
: O 0
Myopic O 0
excimer O 0
laser O 0
PRK O 0
did O 0
not O 0
seem O 0
to O 0
affect O 0
the O 0
posterior O 0
segment O 0
. O 0

The O 0
transient O 0
steroid B-Chemical 0
- O 0
induced O 0
IOP B-Disease 0
rise I-Disease 0
did O 0
not O 0
seem O 0
to O 0
cause O 0
functional O 0
impairment O 0
. O 0

Neutrophil O 0
superoxide B-Chemical 0
and O 0
hydrogen B-Chemical 0
peroxide I-Chemical 0
production 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

Defects O 0
in O 0
superoxide B-Chemical 0
and O 0
hydrogen B-Chemical 0
peroxide I-Chemical 0
production O 0
may O 0
be O 0
implicated O 0
in O 0
the O 0
high O 0
incidence O 0
of O 0
bacterial B-Disease 0
infections I-Disease 0
in O 0
patients O 0
with O 0
acute B-Disease 0
liver I-Disease 0
failure I-Disease 0
( O 0
ALF B-Disease 0
) O 0
. O 0

In O 0
the O 0
present O 0
study O 0
, O 0
oxygen B-Chemical 0
radical O 0
production O 0
in O 0
patients O 0
with O 0
ALF B-Disease 0
due O 0
to O 0
paracetamol B-Chemical 0
overdose B-Disease 0
was O 0
compared O 0
with O 0
that O 0
of O 0
healthy O 0
volunteers O 0
. O 0

Neutrophils O 0
from O 0
14 O 0
ALF B-Disease 0
patients O 0
were O 0
stimulated O 0
via O 0
the O 0
complement O 0
receptors O 0
using O 0
zymosan O 0
opsonized O 0
with O 0
ALF B-Disease 0
or O 0
control O 0
serum O 0
. O 0

Superoxide B-Chemical 0
and O 0
hydrogen B-Chemical 0
peroxide I-Chemical 0
production O 0
by O 0
ALF B-Disease 0
neutrophils O 0
stimulated O 0
with O 0
zymosan O 0
opsonized O 0
with O 0
ALF B-Disease 0
serum O 0
was O 0
significantly O 0
reduced O 0
compared O 0
with O 0
the 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
. O 0

This O 0
defect O 0
persisted O 0
when O 0
zymosan O 0
opsonized O 0
by O 0
control O 0
serum O 0
was O 0
used O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
. O 0

Superoxide B-Chemical 0
and O 0
hydrogen B-Chemical 0
peroxide I-Chemical 0
production O 0
in O 0
neutrophils O 0
stimulated O 0
with O 0
formyl B-Chemical 0
- I-Chemical 0
methionyl I-Chemical 0
- I-Chemical 0
leucyl I-Chemical 0
- I-Chemical 0
phenylalanine I-Chemical 0
( O 0
fMLP B-Chemical 0
) O 0
from O 0
a O 0
further O 0
18 O 0
ALF B-Disease 0
patients O 0
was O 0
unaffected O 0
compared O 0
with O 0
control O 0
neutrophils O 0
. O 0

Serum O 0
C3 O 0
complement O 0
levels O 0
were O 0
significantly O 0
reduced O 0
in O 0
ALF B-Disease 0
patients O 0
compared O 0
with O 0
control O 0
subjects O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
0005 O 0
) O 0
. O 0

These O 0
results O 0
demonstrate O 0
a O 0
neutrophil O 0
defect O 0
in O 0
ALF B-Disease 0
due O 0
to O 0
paracetamol B-Chemical 0
overdose B-Disease 0
, O 0
that O 0
is O 0
complement O 0
dependent O 0
but O 0
independent O 0
of O 0
serum O 0
complement O 0
, O 0
possibly O 0
connected O 0
to O 0
the O 0
complement O 0
receptor O 0
. O 0

Cholesteryl B-Chemical 0
hemisuccinate I-Chemical 0
treatment O 0
protects O 0
rodents O 0
from O 0
the O 0
toxic O 0
effects O 0
of O 0
acetaminophen B-Chemical 0
, O 0
adriamycin B-Chemical 0
, O 0
carbon B-Chemical 0
tetrachloride I-Chemical 0
, O 0
chloroform B-Chemical 0
and O 0
galactosamine B-Chemical 0
. O 0

In O 0
addition O 0
to O 0
its O 0
use O 0
as O 0
a O 0
stabilizer O 0
/ O 0
rigidifier O 0
of O 0
membranes O 0
, O 0
cholesteryl B-Chemical 0
hemisuccinate I-Chemical 0
, O 0
tris B-Chemical 0
salt I-Chemical 0
( O 0
CS B-Chemical 0
) O 0
administration O 0
has O 0
also O 0
been O 0
shown O 0
to O 0
protect O 0
rats O 0
from O 0
the O 0
hepatotoxic B-Disease 0
effects O 0
of O 0
carbon B-Chemical 0
tetrachloride I-Chemical 0
( O 0
CCl4 B-Chemical 0
) O 0
. O 0

To O 0
further O 0
our O 0
understanding O 0
of O 0
the O 0
mechanism O 0
of O 0
CS B-Chemical 0
cytoprotection O 0
, O 0
we O 0
examined O 0
in O 0
rats O 0
and O 0
mice O 0
the O 0
protective O 0
abilities O 0
of O 0
CS B-Chemical 0
and O 0
the O 0
non O 0
- O 0
hydrolyzable O 0
ether O 0
form O 0
of O 0
CS B-Chemical 0
, O 0
gamma B-Chemical 0
- I-Chemical 0
cholesteryloxybutyric I-Chemical 0
acid I-Chemical 0
, O 0
tris B-Chemical 0
salt I-Chemical 0
( O 0
CSE B-Chemical 0
) O 0
against O 0
acetaminophen B-Chemical 0
- O 0
, O 0
adriamycin B-Chemical 0
- O 0
, O 0
carbon B-Chemical 0
tetrachloride I-Chemical 0
- O 0
, O 0
chloroform B-Chemical 0
- O 0
and O 0
galactosamine B-Chemical 0
- O 0
induced O 0
toxicity B-Disease 0
. O 0

The O 0
results O 0
of O 0
these O 0
studies O 0
demonstrated O 0
that O 0
CS B-Chemical 0
- O 0
mediated O 0
protection O 0
is O 0
not O 0
selective O 0
for O 0
a O 0
particular O 0
species O 0
, O 0
organ O 0
system O 0
or O 0
toxic O 0
chemical O 0
. O 0

A O 0
24 O 0
- O 0
h O 0
pretreatment O 0
of O 0
both O 0
rats O 0
and O 0
mice O 0
with O 0
a O 0
single O 0
dose O 0
of O 0
CS B-Chemical 0
( O 0
100mg O 0
/ O 0
kg O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
, O 0
resulted O 0
in O 0
significant O 0
protection O 0
against O 0
the O 0
hepatotoxic B-Disease 0
effects O 0
of O 0
CCl4 B-Chemical 0
, O 0
CHCl3 B-Chemical 0
, O 0
acetaminophen B-Chemical 0
and O 0
galactosamine B-Chemical 0
and O 0
against O 0
the O 0
lethal O 0
( O 0
and O 0
presumably O 0
cardiotoxic B-Disease 0
) O 0
effect O 0
of O 0
adriamycin B-Chemical 0
administration O 0
. O 0

Maximal O 0
CS B-Chemical 0
- O 0
mediated O 0
protection O 0
was O 0
observed O 0
in O 0
experimental O 0
animals O 0
pretreated O 0
24 O 0
h O 0
prior O 0
to O 0
the O 0
toxic O 0
insult O 0
. O 0

These O 0
data O 0
suggest O 0
that O 0
CS B-Chemical 0
intervenes O 0
in O 0
a O 0
critical O 0
cellular O 0
event O 0
that O 0
is O 0
an O 0
important O 0
common O 0
pathway O 0
to O 0
toxic O 0
cell O 0
death O 0
. O 0

The O 0
mechanism O 0
of O 0
CS B-Chemical 0
protection O 0
does O 0
not O 0
appear O 0
to O 0
be O 0
dependent O 0
on O 0
the O 0
inhibition O 0
of O 0
chemical O 0
bioactivation O 0
to O 0
a O 0
toxic O 0
reactive O 0
intermediate O 0
( O 0
in O 0
light O 0
of O 0
the O 0
protection O 0
observed O 0
against O 0
galactosamine B-Chemical 0
hepatotoxicity B-Disease 0
) O 0
. O 0

However O 0
, O 0
based O 0
on O 0
the O 0
data O 0
presented O 0
, O 0
we O 0
can O 0
not O 0
exclude O 0
the O 0
possibility O 0
that O 0
CS B-Chemical 0
administration O 0
inhibits O 0
chemical O 0
bioactivation O 0
. O 0

Our O 0
findings O 0
do O 0
suggest O 0
that O 0
CS B-Chemical 0
- O 0
mediated O 0
protection O 0
is O 0
dependent O 0
on O 0
the O 0
action O 0
of O 0
the O 0
intact O 0
anionic O 0
CS B-Chemical 0
molecule O 0
( O 0
non O 0
- O 0
hydrolyzable O 0
CSE B-Chemical 0
was O 0
as O 0
protective O 0
as O 0
CS B-Chemical 0
) O 0
, O 0
whose O 0
mechanism O 0
has O 0
yet O 0
to O 0
be O 0
defined O 0
. O 0

A O 0
murine O 0
model O 0
of O 0
adenomyosis B-Disease 0
: O 0
the O 0
effects O 0
of O 0
hyperprolactinemia B-Disease 0
induced O 0
by O 0
fluoxetine B-Chemical 0
hydrochloride I-Chemical 0
, O 0
a O 0
selective O 0
serotonin B-Chemical 0
reuptake O 0
inhibitor O 0
, O 0
on O 0
adenomyosis B-Disease 0
induction O 0
in O 0
Wistar O 0
albino O 0
rats O 0
. O 0

OBJECTIVE 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
whether O 0
fluoxetine B-Chemical 0
given O 0
to O 0
castrated O 0
and O 0
noncastrated O 0
rats O 0
caused O 0
hyperprolactinemia B-Disease 0
and O 0
its O 0
effects O 0
with O 0
respect O 0
to O 0
adenomyosis B-Disease 0
. O 0

DESIGN O 0
: O 0
Fluoxetine B-Chemical 0
, O 0
a O 0
serotonin B-Chemical 0
reuptake O 0
inhibitor O 0
, O 0
was O 0
given O 0
to O 0
Wistar O 0
Albino O 0
rats O 0
for O 0
98 O 0
days O 0
to O 0
produce O 0
hyperprolactinemia B-Disease 0
. O 0

The O 0
drug O 0
was O 0
given O 0
to O 0
two O 0
groups O 0
consisting O 0
of O 0
castrated O 0
and O 0
noncastrated O 0
rats O 0
and O 0
compared O 0
to O 0
two O 0
groups O 0
of O 0
castrated O 0
and O 0
noncastrated O 0
controls O 0
. O 0

Prolactin O 0
levels O 0
were O 0
measured O 0
and O 0
the O 0
uteri O 0
of O 0
the O 0
rats O 0
were O 0
removed O 0
for O 0
histopathological O 0
analysis O 0
at O 0
the O 0
end O 0
of O 0
98 O 0
days O 0
. O 0

SETTING O 0
: O 0
Marmara O 0
University O 0
School O 0
of O 0
Medicine O 0
, O 0
Department O 0
of O 0
Histology O 0
and O 0
Embryology O 0
, O 0
Zeynep O 0
Kamil O 0
Women O 0
and O 0
Children O 0
' O 0
s O 0
Hospital O 0
. O 0

MAIN O 0
OUTCOME O 0
MEASURES O 0
: O 0
Serum O 0
prolactin O 0
levels O 0
, O 0
uterine O 0
histopathology O 0
. O 0

RESULTS O 0
: O 0
The O 0
prolactin O 0
levels O 0
of O 0
castrated O 0
and O 0
noncastrated O 0
groups O 0
treated O 0
with O 0
fluoxetine B-Chemical 0
were O 0
statistically O 0
significantly O 0
higher O 0
when O 0
compared O 0
to O 0
their O 0
respective O 0
control O 0
groups O 0
. O 0

Histological O 0
studies O 0
revealed O 0
11 O 0
cases O 0
of O 0
adenomyosis B-Disease 0
, O 0
all O 0
within O 0
the O 0
noncastrated O 0
group O 0
receiving O 0
fluoxetine B-Chemical 0
. O 0

CONCLUSION O 0
: O 0
It O 0
was O 0
suggested O 0
that O 0
high O 0
serum O 0
prolactin O 0
levels O 0
cause O 0
degeneration O 0
of O 0
myometrial O 0
cells O 0
in O 0
the O 0
presence O 0
of O 0
ovarian O 0
steroids B-Chemical 0
that O 0
results O 0
in O 0
a O 0
myometrial O 0
invasion O 0
by O 0
endometrial O 0
stroma O 0
. O 0

This O 0
invasion O 0
eventually O 0
progresses O 0
to O 0
adenomyosis B-Disease 0
. O 0

Postinfarction O 0
ventricular B-Disease 0
septal I-Disease 0
defect I-Disease 0
associated O 0
with O 0
long O 0
- O 0
term O 0
steroid B-Chemical 0
therapy O 0
. O 0

Two O 0
cases O 0
of O 0
postinfarction O 0
ventricular B-Disease 0
septal I-Disease 0
rupture I-Disease 0
in O 0
patients O 0
on O 0
long O 0
- O 0
term O 0
steroid B-Chemical 0
therapy O 0
are O 0
presented O 0
and O 0
the O 0
favourable O 0
outcome O 0
in O 0
both O 0
cases O 0
described O 0
. O 0

A O 0
possible O 0
association O 0
between O 0
steroid B-Chemical 0
therapy O 0
and O 0
subsequent O 0
postinfarction O 0
septal B-Disease 0
rupture I-Disease 0
is O 0
discussed O 0
. O 0

Neuroactive O 0
steroids B-Chemical 0
protect O 0
against O 0
pilocarpine B-Chemical 0
- O 0
and O 0
kainic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
limbic O 0
seizures B-Disease 0
and O 0
status B-Disease 0
epilepticus I-Disease 0
in O 0
mice O 0
. O 0

Several O 0
structurally O 0
related O 0
metabolites O 0
of O 0
progesterone B-Chemical 0
( O 0
3 B-Chemical 0
alpha I-Chemical 0
- I-Chemical 0
hydroxy I-Chemical 0
pregnane I-Chemical 0
- I-Chemical 0
20 I-Chemical 0
- I-Chemical 0
ones I-Chemical 0
) O 0
and O 0
deoxycorticosterone B-Chemical 0
( O 0
3 B-Chemical 0
alpha I-Chemical 0
- I-Chemical 0
hydroxy I-Chemical 0
pregnane I-Chemical 0
- I-Chemical 0
21 I-Chemical 0
- I-Chemical 0
diol I-Chemical 0
- I-Chemical 0
20 I-Chemical 0
- I-Chemical 0
ones I-Chemical 0
) O 0
and O 0
their O 0
3 O 0
beta O 0
- O 0
epimers O 0
were O 0
evaluated O 0
for O 0
protective O 0
activity O 0
against O 0
pilocarpine B-Chemical 0
- O 0
, O 0
kainic B-Chemical 0
acid I-Chemical 0
- O 0
and 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
- O 0
induced O 0
seizures B-Disease 0
in O 0
mice O 0
. O 0

Steroids B-Chemical 0
with O 0
the O 0
3 O 0
- O 0
hydroxy O 0
group O 0
in O 0
the O 0
alpha O 0
- O 0
position O 0
and O 0
5 O 0
- O 0
H O 0
in O 0
the O 0
alpha O 0
- O 0
or O 0
beta O 0
- O 0
configurations O 0
were O 0
highly O 0
effective O 0
in O 0
protecting O 0
against O 0
pilocarpine B-Chemical 0
( O 0
416 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
induced O 0
limbic O 0
motor O 0
seizures B-Disease 0
and O 0
status B-Disease 0
epilepticus I-Disease 0
( O 0
ED50 O 0
values O 0
, O 0
7 O 0
. O 0
0 O 0
- O 0
18 O 0
. O 0
7 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

The O 0
corresponding O 0
epimers O 0
with O 0
the O 0
3 O 0
- O 0
hydroxy O 0
group O 0
in O 0
the O 0
beta O 0
- O 0
position O 0
were O 0
also O 0
effective O 0
but O 0
less O 0
potent O 0
( O 0
ED50 O 0
values O 0
, O 0
33 O 0
. O 0
8 O 0
- O 0
63 O 0
. O 0
5 O 0
, O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

Although O 0
the O 0
neuroactive O 0
steroids B-Chemical 0
were O 0
considerably O 0
less O 0
potent O 0
than O 0
the O 0
benzodiazepine B-Chemical 0
clonazepam B-Chemical 0
in O 0
protecting O 0
against O 0
pilocarpine B-Chemical 0
seizures B-Disease 0
, O 0
steroids B-Chemical 0
with O 0
the O 0
5 O 0
alpha O 0
, O 0
3 O 0
alpha O 0
- O 0
configuration O 0
had O 0
comparable O 0
or O 0
higher O 0
protective O 0
index O 0
values O 0
( O 0
TD50 O 0
for O 0
motor O 0
impairment O 0
divided O 0
by O 0
ED50 O 0
for O 0
seizure B-Disease 0
protection O 0
) O 0
than O 0
clonazepam B-Chemical 0
, O 0
indicating O 0
that O 0
some O 0
neuroactive O 0
steroids B-Chemical 0
may O 0
have O 0
lower O 0
relative O 0
toxicity B-Disease 0
. O 0

Steroids B-Chemical 0
with O 0
the O 0
5 O 0
alpha O 0
, O 0
3 O 0
alpha O 0
- O 0
or O 0
5 O 0
beta O 0
, O 0
3 O 0
alpha O 0
- O 0
configurations O 0
also O 0
produced O 0
a O 0
dose O 0
- O 0
dependent O 0
delay O 0
in O 0
the O 0
onset O 0
of O 0
limbic O 0
seizures B-Disease 0
induced O 0
by O 0
kainic B-Chemical 0
acid I-Chemical 0
( O 0
32 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
but O 0
did O 0
not O 0
completely O 0
protect O 0
against O 0
the O 0
seizures B-Disease 0
. O 0

However O 0
, O 0
when O 0
a O 0
second O 0
dose O 0
of O 0
the O 0
steroid B-Chemical 0
was O 0
administered O 0
1 O 0
hr O 0
after O 0
the O 0
first O 0
dose O 0
, O 0
complete O 0
protection O 0
from O 0
the O 0
kainic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
limbic O 0
seizures B-Disease 0
and O 0
status B-Disease 0
epilepticus I-Disease 0
was O 0
obtained O 0
. O 0

The O 0
steroids B-Chemical 0
also O 0
caused O 0
a O 0
dose O 0
- O 0
dependent O 0
delay O 0
in O 0
NMDA B-Chemical 0
( O 0
257 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
induced O 0
lethality O 0
, O 0
but O 0
did O 0
not O 0
completely O 0
protect O 0
against O 0
NMDA B-Chemical 0
seizures B-Disease 0
or O 0
lethality O 0
. O 0

We O 0
conclude O 0
that O 0
neuroactive O 0
steroids B-Chemical 0
are O 0
highly O 0
effective O 0
in O 0
protecting O 0
against O 0
pilocarpine B-Chemical 0
- O 0
and O 0
kainic B-Chemical 0
acid I-Chemical 0
- O 0
induced O 0
seizures B-Disease 0
and O 0
status B-Disease 0
epilepticus I-Disease 0
in O 0
mice O 0
, O 0
and O 0
may O 0
be O 0
of O 0
utility O 0
in O 0
the O 0
treatment O 0
of O 0
some O 0
forms O 0
of O 0
status B-Disease 0
epilepticus I-Disease 0
in O 0
humans O 0
. O 0

Hepatic O 0
and O 0
extrahepatic O 0
angiotensinogen O 0
gene O 0
expression O 0
in O 0
rats O 0
with O 0
acute O 0
nephrotic B-Disease 0
syndrome I-Disease 0
. O 0

Plasma O 0
concentration O 0
and O 0
urine O 0
excretion O 0
of O 0
the O 0
renin O 0
- O 0
angiotensin B-Chemical 0
system O 0
proteins O 0
are O 0
altered O 0
in O 0
rats O 0
with O 0
nephrotic B-Disease 0
syndrome I-Disease 0
( O 0
NS B-Disease 0
) O 0
. O 0

In O 0
this O 0
work O 0
the O 0
messenger O 0
ribonucleic O 0
acid O 0
( O 0
mRNA O 0
) O 0
levels O 0
of O 0
angiotensinogen O 0
( O 0
Ao O 0
) O 0
were O 0
analyzed O 0
with O 0
the O 0
slot O 0
- O 0
blot O 0
hybridization O 0
technique O 0
in O 0
liver O 0
and O 0
other O 0
extrahepatic O 0
tissues O 0
: O 0
kidney O 0
, O 0
heart O 0
, O 0
brain O 0
, O 0
and O 0
adrenal O 0
gland O 0
from O 0
control O 0
, O 0
nephrotic B-Disease 0
, O 0
and O 0
pair O 0
- O 0
fed O 0
( O 0
PF O 0
) O 0
rats O 0
. O 0

NS B-Disease 0
was O 0
induced O 0
by O 0
a O 0
single O 0
injection O 0
of O 0
puromycin B-Chemical 0
amino I-Chemical 0
- I-Chemical 0
nucleoside I-Chemical 0
( O 0
PAN B-Chemical 0
) O 0
. O 0

Although O 0
a O 0
great O 0
urinary O 0
excretion O 0
and O 0
half O 0
- O 0
normal O 0
plasma O 0
levels O 0
of O 0
Ao O 0
were O 0
observed O 0
on O 0
day O 0
6 O 0
after O 0
PAN B-Chemical 0
injection O 0
, O 0
when O 0
NS B-Disease 0
was O 0
clearly O 0
established O 0
, O 0
hepatic O 0
Ao O 0
mRNA O 0
levels O 0
did O 0
not O 0
change O 0
. O 0

Furthermore O 0
, O 0
the O 0
Ao O 0
mRNA O 0
levels O 0
did O 0
not O 0
change O 0
in O 0
any O 0
of O 0
the O 0
extrahepatic O 0
tissues O 0
studied O 0
on O 0
day O 0
6 O 0
, O 0
nor O 0
did O 0
its O 0
hepatic O 0
levels O 0
at O 0
days O 0
1 O 0
, O 0
3 O 0
, O 0
5 O 0
, O 0
or O 0
7 O 0
after O 0
PAN B-Chemical 0
injection O 0
. O 0

These O 0
data O 0
suggest O 0
that O 0
the O 0
hepatic O 0
and O 0
extrahepatic O 0
Ao O 0
mRNA O 0
levels O 0
are O 0
unaltered O 0
during O 0
the O 0
development O 0
of O 0
the O 0
acute O 0
NS B-Disease 0
induced O 0
by O 0
PAN B-Chemical 0
. O 0

Neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
with O 0
risperidone B-Chemical 0
. O 0

Neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
is O 0
thought O 0
to O 0
be O 0
a O 0
result O 0
of O 0
dopamine B-Chemical 0
D2 O 0
receptor O 0
blockade O 0
in O 0
the O 0
striatum O 0
of O 0
the O 0
basal O 0
ganglia O 0
. O 0

Risperidone B-Chemical 0
, O 0
a O 0
benzisoxazole B-Chemical 0
derivative O 0
antipsychotic O 0
, O 0
has O 0
high O 0
serotonin B-Chemical 0
5 O 0
- O 0
HT2 O 0
receptor O 0
blockade O 0
and O 0
dose O 0
- O 0
related O 0
D2 O 0
receptor O 0
blockade O 0
. O 0

The O 0
high O 0
ratio O 0
is O 0
believed O 0
to O 0
impart O 0
the O 0
low O 0
frequency O 0
of O 0
extrapyramidal B-Disease 0
symptoms I-Disease 0
with O 0
risperidone B-Chemical 0
at O 0
low O 0
dosages O 0
. O 0

With O 0
this O 0
low O 0
frequency O 0
of O 0
extrapyramidal B-Disease 0
symptoms I-Disease 0
, O 0
it O 0
was O 0
thought O 0
the O 0
frequency O 0
of O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
might O 0
also O 0
be O 0
lowered O 0
. O 0

A O 0
73 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
developed O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
after O 0
monotherapy O 0
with O 0
risperidone B-Chemical 0
. O 0

The O 0
syndrome O 0
reversed O 0
after O 0
discontinuing O 0
risperidone B-Chemical 0
and O 0
starting O 0
treatment O 0
with O 0
dantrolene B-Chemical 0
and O 0
bromocriptine B-Chemical 0
. O 0

It O 0
appears O 0
that O 0
the O 0
protection O 0
from O 0
extrapyramidal O 0
side O 0
effects O 0
observed O 0
with O 0
risperidone B-Chemical 0
does O 0
not O 0
ensure O 0
protection O 0
from O 0
neuroleptic B-Disease 0
malignant I-Disease 0
syndrome I-Disease 0
. O 0

The O 0
attenuating O 0
effect O 0
of O 0
carteolol B-Chemical 0
hydrochloride I-Chemical 0
, O 0
a O 0
beta O 0
- O 0
adrenoceptor O 0
antagonist O 0
, O 0
on O 0
neuroleptic O 0
- O 0
induced O 0
catalepsy B-Disease 0
in O 0
rats O 0
. O 0

It O 0
is O 0
known O 0
that O 0
beta O 0
- O 0
adrenoceptor O 0
antagonists O 0
are O 0
effective O 0
in O 0
the O 0
treatment O 0
of O 0
akathisia B-Disease 0
, O 0
one O 0
of O 0
the O 0
extrapyramidal O 0
side O 0
effects O 0
that O 0
occur O 0
during O 0
neuroleptic O 0
treatment O 0
. O 0

Neuroleptic O 0
- O 0
induced O 0
catalepsy B-Disease 0
, O 0
a O 0
model O 0
of O 0
neuroleptic O 0
- O 0
induced O 0
extrapyramidal O 0
side O 0
effects O 0
, O 0
was O 0
considered O 0
suitable O 0
as O 0
a O 0
model O 0
for O 0
predicting O 0
neuroleptic O 0
- O 0
induced O 0
akathisia B-Disease 0
in O 0
humans O 0
, O 0
although O 0
neuroleptic O 0
- O 0
induced O 0
catalepsy B-Disease 0
was O 0
not O 0
considered O 0
a O 0
specific O 0
test O 0
for O 0
neuroleptic O 0
- O 0
induced O 0
akathisia B-Disease 0
. O 0

Therefore O 0
, O 0
the O 0
effects O 0
of O 0
carteolol B-Chemical 0
, O 0
a O 0
beta O 0
- O 0
adrenoceptor O 0
antagonist O 0
, O 0
on O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
in O 0
rats O 0
were O 0
behaviorally O 0
studied O 0
and O 0
compared O 0
with O 0
those O 0
of O 0
propranolol B-Chemical 0
and O 0
biperiden B-Chemical 0
, O 0
a O 0
muscarinic O 0
receptor O 0
antagonist O 0
. O 0

Carteolol B-Chemical 0
, O 0
as O 0
well O 0
as O 0
propranolol B-Chemical 0
and O 0
biperiden B-Chemical 0
, O 0
inhibited O 0
the O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
. O 0

The O 0
inhibitory O 0
effect O 0
of O 0
carteolol B-Chemical 0
was O 0
almost O 0
comparable O 0
to O 0
that O 0
of O 0
propranolol B-Chemical 0
, O 0
but O 0
was O 0
weaker O 0
than O 0
that O 0
of O 0
biperiden B-Chemical 0
. O 0

Carteolol B-Chemical 0
did O 0
not O 0
evoke O 0
postsynaptic O 0
dopamine B-Chemical 0
receptor O 0
- O 0
stimulating O 0
behavioral O 0
signs O 0
such O 0
as O 0
stereotypy O 0
and O 0
hyperlocomotion B-Disease 0
in O 0
rats O 0
. O 0

Carteolol B-Chemical 0
did O 0
not O 0
antagonize O 0
the O 0
inhibitory O 0
effects O 0
of O 0
haloperidol B-Chemical 0
on O 0
apomorphine B-Chemical 0
- O 0
induced O 0
stereotypy O 0
and O 0
locomotor O 0
activity O 0
in O 0
rats O 0
. O 0

In O 0
addition O 0
, O 0
carteolol B-Chemical 0
did O 0
not O 0
evoke O 0
5 O 0
- O 0
HT1A O 0
receptor O 0
- O 0
stimulating O 0
behavioral O 0
signs O 0
such O 0
as O 0
flat O 0
body O 0
posture O 0
and O 0
forepaw O 0
treading O 0
and O 0
did O 0
not O 0
inhibit O 0
5 B-Chemical 0
- I-Chemical 0
hydroxytryptophan I-Chemical 0
- O 0
induced O 0
head O 0
twitch O 0
in O 0
rats O 0
. O 0

Finally O 0
, O 0
carteolol B-Chemical 0
did O 0
not O 0
inhibit O 0
physostigmine B-Chemical 0
- O 0
induced O 0
lethality O 0
in O 0
rats O 0
. O 0

These O 0
results O 0
strongly O 0
suggest O 0
that O 0
carteolol B-Chemical 0
improves O 0
haloperidol B-Chemical 0
- O 0
induced O 0
catalepsy B-Disease 0
via O 0
its O 0
beta O 0
- O 0
adrenoceptor O 0
antagonistic O 0
activity O 0
and O 0
is O 0
expected O 0
to O 0
be O 0
effective O 0
in O 0
the O 0
treatment O 0
of O 0
akathisia B-Disease 0
without O 0
attenuating O 0
neuroleptic O 0
- O 0
induced O 0
antipsychotic O 0
effects O 0
due O 0
to O 0
its O 0
postsynaptic O 0
dopamine B-Chemical 0
receptor O 0
antagonistic O 0
activity O 0
. O 0

Granulosa B-Disease 0
cell I-Disease 0
tumor I-Disease 0
of I-Disease 0
the I-Disease 0
ovary I-Disease 0
associated O 0
with O 0
antecedent O 0
tamoxifen B-Chemical 0
use O 0
. O 0

BACKGROUND O 0
: O 0
Increased O 0
attention O 0
has O 0
been O 0
focused O 0
recently O 0
on O 0
the O 0
estrogenic O 0
effects O 0
of O 0
tamoxifen B-Chemical 0
. O 0

Review O 0
of O 0
the O 0
literature O 0
reveals O 0
an O 0
association O 0
between O 0
tamoxifen B-Chemical 0
use O 0
and O 0
gynecologic O 0
tumors B-Disease 0
. O 0

CASE O 0
: O 0
A O 0
52 O 0
- O 0
year O 0
- O 0
old O 0
postmenopausal O 0
woman O 0
was O 0
treated O 0
with O 0
tamoxifen B-Chemical 0
for O 0
stage O 0
II O 0
estrogen B-Chemical 0
receptor O 0
- O 0
positive O 0
breast B-Disease 0
carcinoma I-Disease 0
. O 0

Her O 0
aspartate B-Chemical 0
transaminase O 0
and O 0
alanine B-Chemical 0
transaminase O 0
levels O 0
increase O 0
markedly O 0
after O 0
6 O 0
months O 0
of O 0
tamoxifen B-Chemical 0
use O 0
. O 0

After O 0
an O 0
additional O 0
17 O 0
months O 0
of O 0
elevated O 0
serum O 0
transaminases O 0
, O 0
the O 0
patient O 0
was O 0
found O 0
to O 0
have O 0
a O 0
stage O 0
Ic O 0
granulosa B-Disease 0
cell I-Disease 0
tumor I-Disease 0
of I-Disease 0
the I-Disease 0
ovary I-Disease 0
. O 0

CONCLUSION O 0
: O 0
Patients O 0
with O 0
tamoxifen B-Chemical 0
- O 0
induced O 0
liver B-Disease 0
dysfunction I-Disease 0
may O 0
be O 0
at O 0
increased O 0
risk O 0
for O 0
granulosa B-Disease 0
cell I-Disease 0
tumors I-Disease 0
because O 0
of O 0
alterations O 0
in O 0
tamoxifen B-Chemical 0
metabolism O 0
. O 0

Lifetime O 0
treatment O 0
of O 0
mice O 0
with O 0
azidothymidine B-Chemical 0
( O 0
AZT B-Chemical 0
) O 0
produces O 0
myelodysplasia B-Disease 0
. O 0

AZT B-Chemical 0
has O 0
induced O 0
a O 0
macrocytic B-Disease 0
anemia I-Disease 0
in O 0
AIDS B-Disease 0
patients O 0
on O 0
long O 0
term O 0
AZT B-Chemical 0
therapy O 0
. O 0

It O 0
is O 0
generally O 0
assumed O 0
that O 0
DNA O 0
elongation O 0
is O 0
stopped O 0
by O 0
the O 0
insertion O 0
of O 0
AZT B-Chemical 0
into O 0
the O 0
chain O 0
in O 0
place O 0
of O 0
thymidine B-Chemical 0
thus O 0
preventing O 0
the O 0
phosphate B-Chemical 0
hydroxyl O 0
linkages O 0
and O 0
therefore O 0
suppresses O 0
hemopoietic O 0
progenitor O 0
cell O 0
proliferation O 0
in O 0
an O 0
early O 0
stage O 0
of O 0
differentiation O 0
. O 0

CBA O 0
/ O 0
Ca O 0
male O 0
mice O 0
started O 0
on O 0
AZT B-Chemical 0
0 O 0
. O 0
75 O 0
mg O 0
/ O 0
ml O 0
H2O O 0
at O 0
84 O 0
days O 0
of O 0
age O 0
and O 0
kept O 0
on O 0
it O 0
for O 0
687 O 0
days O 0
when O 0
dosage O 0
reduced O 0
to O 0
0 O 0
. O 0
5 O 0
mg O 0
/ O 0
ml O 0
H2O O 0
for O 0
a O 0
group O 0
, O 0
another O 0
group O 0
removed O 0
from O 0
AZT B-Chemical 0
to O 0
see O 0
recovery O 0
, O 0
and O 0
third O 0
group O 0
remained O 0
on O 0
0 O 0
. O 0
75 O 0
mg O 0
. O 0

At O 0
687 O 0
days O 0
mice O 0
that O 0
had O 0
been O 0
on O 0
0 O 0
. O 0
75 O 0
mg O 0
had O 0
average O 0
platelet O 0
counts O 0
of O 0
2 O 0
. O 0
5 O 0
x O 0
10 O 0
( O 0
6 O 0
) O 0
. O 0

Histological O 0
examination O 0
on O 0
9 O 0
of O 0
10 O 0
mice O 0
with O 0
such O 0
thrombocytopenia B-Disease 0
showed O 0
changes O 0
compatible O 0
with O 0
myelodysplastic B-Disease 0
syndrome I-Disease 0
( O 0
MDS B-Disease 0
) O 0
. O 0

A O 0
variety O 0
of O 0
histological O 0
patterns O 0
was O 0
observed O 0
. O 0

There O 0
were O 0
two O 0
cases O 0
of O 0
hypocellular O 0
myelodysplasia B-Disease 0
, O 0
two O 0
cases O 0
of O 0
hypersegmented O 0
myelodysplastic B-Disease 0
granulocytosis O 0
, O 0
two O 0
cases O 0
of O 0
hypercellular O 0
marrow O 0
with O 0
abnormal O 0
megakaryocytes O 0
with O 0
bizarre O 0
nuclei O 0
, O 0
one O 0
case O 0
of O 0
megakaryocytic O 0
myelosis O 0
associated O 0
with O 0
a O 0
hyperplastic B-Disease 0
marrow I-Disease 0
, O 0
dysmyelopoiesis B-Disease 0
and O 0
a O 0
hypocellular B-Disease 0
marrow I-Disease 0
and O 0
two O 0
cases O 0
of O 0
myelodysplasia B-Disease 0
with O 0
dyserythropoiesis B-Disease 0
, O 0
hemosiderosis B-Disease 0
and O 0
a O 0
hypocellular B-Disease 0
marrow I-Disease 0
. O 0

Above O 0
mentioned O 0
AZT B-Chemical 0
incorporation O 0
may O 0
have O 0
induced O 0
an O 0
ineffective O 0
hemopoiesis O 0
in O 0
the O 0
primitive O 0
hemopoietic O 0
progenitor O 0
cells O 0
, O 0
which O 0
is O 0
known O 0
to O 0
be O 0
seen O 0
commonly O 0
in O 0
the O 0
myelodysplastic B-Disease 0
syndrome I-Disease 0
. O 0

Biphasic O 0
response O 0
of O 0
the O 0
SA O 0
node O 0
of O 0
the O 0
dog O 0
heart O 0
in O 0
vivo O 0
to O 0
selective O 0
administration O 0
of O 0
ketamine B-Chemical 0
. O 0

Effect O 0
of O 0
ketamine B-Chemical 0
on O 0
the O 0
SA O 0
node O 0
of O 0
the O 0
dog O 0
heart O 0
was O 0
studied O 0
in O 0
vivo O 0
using O 0
a O 0
selective O 0
perfusion O 0
technique O 0
of O 0
the O 0
SA O 0
node O 0
artery O 0
. O 0

Injections O 0
of O 0
ketamine B-Chemical 0
in O 0
doses O 0
from O 0
100 O 0
microgram O 0
to O 0
3 O 0
mg O 0
into O 0
the O 0
artery O 0
produced O 0
a O 0
depression B-Disease 0
of O 0
the O 0
SA O 0
nodal O 0
activity O 0
by O 0
a O 0
direct O 0
action O 0
. O 0

This O 0
depression B-Disease 0
was O 0
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appearance O 0
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phase O 0
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Bilateral O 0
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ketamine B-Chemical 0
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it O 0
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This O 0
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. O 0

Over O 0
expression O 0
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estrogen B-Chemical 0
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Estrogens B-Chemical 0
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Fischer O 0
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The O 0
mechanistic O 0
details O 0
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To O 0
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Western O 0
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The O 0
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2 O 0
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The O 0
results O 0
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17beta B-Chemical 0
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The O 0
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VEGF O 0
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VPF O 0
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After O 0
15 O 0
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The O 0
function O 0
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Furthermore O 0
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These O 0
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Persistent O 0
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We O 0
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case O 0
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Ten O 0
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he O 0
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He O 0
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have O 0
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vasopressin B-Chemical 0
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polyuria B-Disease 0
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patient O 0
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lithium B-Chemical 0
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We O 0
discuss O 0
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mechanisms O 0
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Effects O 0
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The O 0
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2020 I-Chemical 0
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247 I-Chemical 0
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E B-Chemical 0
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2020 I-Chemical 0
all O 0
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1 O 0
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In O 0
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2020 I-Chemical 0
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All O 0
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. O 0

Moreover O 0
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All O 0
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The O 0
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These O 0
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The O 0
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247 I-Chemical 0
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Potential O 0
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The O 0
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chloro I-Chemical 0
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7 I-Chemical 0
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8 I-Chemical 0
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dihydroxy I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
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allyl I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
phenyl 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
5 I-Chemical 0
- I-Chemical 0
tetrahydro I-Chemical 0
- I-Chemical 0
1H I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
benzaze I-Chemical 0
pine I-Chemical 0
hydrobromide I-Chemical 0
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A B-Chemical 0
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77636 I-Chemical 0
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3 I-Chemical 0
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] I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
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aminomethyl I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
, I-Chemical 0
4 I-Chemical 0
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dihydro I-Chemical 0
- I-Chemical 0
5 I-Chemical 0
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6 I-Chemical 0
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dihydroxy I-Chemical 0
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1H I-Chemical 0
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2 I-Chemical 0
- I-Chemical 0
benzo I-Chemical 0
pyran I-Chemical 0
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We O 0
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1 B-Chemical 0
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- I-Chemical 0
4 I-Chemical 0
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phenyl I-Chemical 0
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1 I-Chemical 0
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2 I-Chemical 0
, I-Chemical 0
3 I-Chemical 0
, I-Chemical 0
6 I-Chemical 0
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tetrahydropyridine I-Chemical 0
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MPTP B-Chemical 0
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exhibit O 0
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dyskinesias B-Disease 0
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evaluate O 0
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dyskinetic B-Disease 0
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] I-Chemical 0
- I-Chemical 0
4 I-Chemical 0
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5 I-Chemical 0
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5a I-Chemical 0
, I-Chemical 0
6 I-Chemical 0
, I-Chemical 0
7 I-Chemical 0
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11b I-Chemical 0
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hexahydro I-Chemical 0
- I-Chemical 0
2 I-Chemical 0
- I-Chemical 0
propyl I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
thia I-Chemical 0
- I-Chemical 0
5 I-Chemical 0
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+ I-Chemical 0
+ I-Chemical 0
+ I-Chemical 0
azacyclopent I-Chemical 0
- I-Chemical 0
1 I-Chemical 0
- I-Chemical 0
ena I-Chemical 0
[ I-Chemical 0
c I-Chemical 0
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phenathrene I-Chemical 0
- I-Chemical 0
9 I-Chemical 0
- I-Chemical 0
10 I-Chemical 0
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diol I-Chemical 0
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Levodopa B-Chemical 0
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- I-Chemical 0
trans I-Chemical 0
] I-Chemical 0
- I-Chemical 0
4 I-Chemical 0
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4a I-Chemical 0
, I-Chemical 0
5 I-Chemical 0
, I-Chemical 0
6 I-Chemical 0
, I-Chemical 0
7 I-Chemical 0
, I-Chemical 0
8 I-Chemical 0
, I-Chemical 0
8a I-Chemical 0
, I-Chemical 0
9 I-Chemical 0
- I-Chemical 0
o I-Chemical 0
- I-Chemical 0
dihydro I-Chemical 0
- I-Chemical 0
5n I-Chemical 0
- I-Chemical 0
propyl I-Chemical 0
- I-Chemical 0
2H I-Chemical 0
- I-Chemical 0
pyrazo I-Chemical 0
lo I-Chemical 0
- I-Chemical 0
3 I-Chemical 0
- I-Chemical 0
4 I-Chemical 0
- I-Chemical 0
quinoline I-Chemical 0
hydrochloride I-Chemical 0
) O 0
were O 0
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. O 0

Acute O 0
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of O 0
A B-Chemical 0
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MPTP B-Chemical 0
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parkinsonism B-Disease 0
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levodopa B-Chemical 0
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LY B-Chemical 0
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171555 I-Chemical 0
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was O 0
less O 0
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to O 0
reproduce O 0
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in O 0
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with O 0
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LY B-Chemical 0
- I-Chemical 0
171555 I-Chemical 0
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subsequent O 0
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compared O 0
with O 0
levodopa B-Chemical 0
and O 0
selective O 0
DA B-Chemical 0
D2 O 0
receptor O 0
agonist O 0
. O 0

Potent O 0
DA B-Chemical 0
D1 O 0
receptor O 0
agents O 0
with O 0
an O 0
intermediate O 0
duration O 0
of O 0
efficacy O 0
such O 0
as O 0
A B-Chemical 0
- I-Chemical 0
86929 I-Chemical 0
( O 0
approximately O 0
4 O 0
hr O 0
at O 0
higher O 0
doses O 0
tested O 0
) O 0
are O 0
potential O 0
therapeutic O 0
tools O 0
in O 0
PD B-Disease 0
and O 0
merit O 0
further O 0
attention O 0
. O 0

Neuropeptide O 0
- O 0
Y O 0
immunoreactivity 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

Neuropeptide O 0
- O 0
Y O 0
( O 0
NPY O 0
) O 0
is O 0
expressed O 0
by O 0
granule O 0
cells O 0
and O 0
mossy O 0
fibres O 0
of O 0
the O 0
hippocampal O 0
dentate O 0
gyrus O 0
during O 0
experimental O 0
temporal B-Disease 0
lobe I-Disease 0
epilepsy I-Disease 0
( O 0
TLE B-Disease 0
) O 0
. O 0

This O 0
expression O 0
may O 0
represent O 0
an O 0
endogenous O 0
damping O 0
mechanism O 0
since O 0
NPY O 0
has O 0
been O 0
shown O 0
to O 0
block O 0
seizure B-Disease 0
- O 0
like O 0
events O 0
following O 0
high O 0
- O 0
frequency O 0
stimulation O 0
in O 0
hippocampal O 0
slices O 0
. O 0

The O 0
pilocarpine B-Chemical 0
( O 0
PILO B-Chemical 0
) O 0
model O 0
of O 0
epilepsy B-Disease 0
is O 0
characterized O 0
by O 0
an O 0
acute O 0
period O 0
of O 0
status B-Disease 0
epilepticus I-Disease 0
followed O 0
by O 0
spontaneous O 0
recurrent O 0
seizures B-Disease 0
and O 0
related O 0
brain B-Disease 0
damage I-Disease 0
. O 0

We O 0
report O 0
peroxidase O 0
- O 0
antiperoxidase O 0
immunostaining O 0
for O 0
NPY O 0
in O 0
several O 0
brain O 0
regions O 0
in O 0
this O 0
model O 0
. O 0

PILO B-Chemical 0
- O 0
injected O 0
animals O 0
exhibited O 0
NPY O 0
immunoreactivity O 0
in O 0
the O 0
region O 0
of O 0
the O 0
mossy O 0
fibre O 0
terminals O 0
, O 0
in O 0
the O 0
dentate O 0
gyrus O 0
inner O 0
molecular O 0
layer O 0
and O 0
, O 0
in O 0
a O 0
few O 0
cases O 0
, O 0
within O 0
presumed O 0
granule O 0
cells O 0
. O 0

NPY O 0
immunoreactivity O 0
was O 0
also O 0
dramatically O 0
changed O 0
in O 0
the O 0
entorhinal O 0
cortex O 0
, O 0
amygdala O 0
and O 0
sensorimotor O 0
areas O 0
. O 0

In O 0
addition O 0
, O 0
PILO B-Chemical 0
injected O 0
animals O 0
exhibited O 0
a O 0
reduction O 0
in O 0
the O 0
number O 0
of O 0
NPY O 0
- O 0
immunoreactive O 0
interneurons O 0
compared O 0
with O 0
controls O 0
. O 0

The O 0
results O 0
demonstrate O 0
that O 0
changes O 0
in O 0
NPY O 0
expression O 0
, O 0
including O 0
expression O 0
in O 0
the O 0
granule O 0
cells O 0
and O 0
mossy O 0
fibres O 0
and O 0
the O 0
loss O 0
of O 0
vulnerable O 0
NPY O 0
neurons O 0
, O 0
are O 0
present O 0
in O 0
the O 0
PILO B-Chemical 0
model O 0
of O 0
TLE B-Disease 0
. O 0

However O 0
, O 0
the O 0
significance O 0
of O 0
this O 0
changed O 0
synthesis O 0
of O 0
NPY O 0
remains O 0
to O 0
be O 0
determined O 0
. O 0

Posteroventral O 0
medial O 0
pallidotomy O 0
in O 0
advanced O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Posteroventral O 0
medial O 0
pallidotomy O 0
sometimes O 0
produces O 0
striking O 0
improvement O 0
in O 0
patients O 0
with O 0
advanced O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
, O 0
but O 0
the O 0
studies O 0
to O 0
date O 0
have O 0
involved O 0
small O 0
numbers O 0
of O 0
patients O 0
and O 0
short O 0
- O 0
term O 0
follow O 0
- O 0
up O 0
. O 0

METHODS O 0
: O 0
Forty O 0
patients O 0
with O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
underwent O 0
serial O 0
, O 0
detailed O 0
assessments O 0
both O 0
after O 0
drug O 0
withdrawal O 0
( O 0
" O 0
off O 0
" O 0
period O 0
) O 0
and O 0
while O 0
taking O 0
their O 0
optimal O 0
medical O 0
regimens O 0
( O 0
" O 0
on O 0
" O 0
period O 0
) O 0
. O 0

All O 0
patients O 0
were O 0
examined O 0
preoperatively O 0
and O 0
39 O 0
were O 0
examined O 0
at O 0
six O 0
months O 0
; O 0
27 O 0
of O 0
the O 0
patients O 0
were O 0
also O 0
examined O 0
at O 0
one O 0
year O 0
, O 0
and O 0
11 O 0
at O 0
two O 0
years O 0
. O 0

RESULTS O 0
: O 0
The O 0
percent O 0
improvements O 0
at O 0
six O 0
months O 0
were O 0
as O 0
follows O 0
: O 0
off O 0
- O 0
period O 0
score O 0
for O 0
overall O 0
motor O 0
function O 0
, O 0
28 O 0
percent O 0
( O 0
95 O 0
percent O 0
confidence O 0
interval O 0
, O 0
19 O 0
to O 0
38 O 0
percent O 0
) O 0
, O 0
with O 0
most O 0
of O 0
the O 0
improvement O 0
in O 0
the O 0
contralateral O 0
limbs O 0
; O 0
off O 0
- O 0
period O 0
score O 0
for O 0
activities O 0
of O 0
daily O 0
living O 0
, O 0
29 O 0
percent O 0
( O 0
95 O 0
percent O 0
confidence O 0
interval O 0
, O 0
19 O 0
to O 0
39 O 0
percent O 0
) O 0
; O 0
on O 0
- O 0
period O 0
score O 0
for O 0
contralateral O 0
dyskinesias B-Disease 0
, O 0
82 O 0
percent O 0
( O 0
95 O 0
percent O 0
confidence O 0
interval O 0
, O 0
72 O 0
to O 0
91 O 0
percent O 0
) O 0
; O 0
and O 0
on O 0
- O 0
period O 0
score O 0
for O 0
ipsilateral O 0
dyskinesias B-Disease 0
, O 0
44 O 0
percent O 0
( O 0
95 O 0
percent O 0
confidence O 0
interval O 0
, O 0
29 O 0
to O 0
59 O 0
percent O 0
) O 0
. O 0

The O 0
improvements O 0
in O 0
dyskinesias B-Disease 0
and O 0
the O 0
total O 0
scores O 0
for O 0
off O 0
- O 0
period O 0
parkinsonism B-Disease 0
, O 0
contralateral O 0
bradykinesia B-Disease 0
, O 0
and O 0
rigidity B-Disease 0
were O 0
sustained O 0
in O 0
the O 0
11 O 0
patients O 0
examined O 0
at O 0
two O 0
years O 0
. O 0

The O 0
improvement O 0
in O 0
ipsilateral O 0
dyskinesias B-Disease 0
was O 0
lost O 0
after O 0
one O 0
year O 0
, O 0
and O 0
the O 0
improvements O 0
in O 0
postural O 0
stability O 0
and O 0
gait O 0
lasted O 0
only O 0
three O 0
to O 0
six O 0
months O 0
. O 0

Approximately O 0
half O 0
the O 0
patients O 0
who O 0
had O 0
been O 0
dependent O 0
on O 0
assistance O 0
in O 0
activities O 0
of O 0
daily O 0
living O 0
in O 0
the O 0
off O 0
period O 0
before O 0
surgery O 0
became O 0
independent O 0
after O 0
surgery O 0
. O 0

The O 0
complications O 0
of O 0
surgery O 0
were O 0
generally O 0
well O 0
tolerated O 0
, O 0
and O 0
there O 0
were O 0
no O 0
significant O 0
changes O 0
in O 0
the O 0
use O 0
of O 0
medication O 0
. O 0

CONCLUSIONS O 0
: O 0
In O 0
late O 0
- O 0
stage O 0
Parkinson B-Disease 0
' I-Disease 0
s I-Disease 0
disease I-Disease 0
, O 0
pallidotomy O 0
significantly O 0
reduces O 0
levodopa B-Chemical 0
- O 0
induced O 0
dyskinesias B-Disease 0
and O 0
off O 0
- O 0
period O 0
disability O 0
. O 0

Much O 0
of O 0
the O 0
benefit O 0
is O 0
sustained O 0
at O 0
two O 0
years O 0
, O 0
although O 0
some O 0
improvements O 0
, O 0
such O 0
as O 0
those O 0
on O 0
the O 0
ipsilateral O 0
side O 0
and O 0
in O 0
axial O 0
symptoms O 0
, O 0
wane O 0
within O 0
the O 0
first O 0
year O 0
. O 0

The O 0
on O 0
- O 0
period O 0
symptoms O 0
that O 0
are O 0
resistant O 0
to O 0
dopaminergic O 0
therapy O 0
do O 0
not O 0
respond O 0
to O 0
pallidotomy O 0
. O 0

Clarithromycin B-Chemical 0
- O 0
induced O 0
ventricular B-Disease 0
tachycardia I-Disease 0
. O 0

Clarithromycin B-Chemical 0
is O 0
a O 0
relatively O 0
new O 0
macrolide B-Chemical 0
antibiotic O 0
that O 0
offers O 0
twice O 0
- O 0
daily O 0
dosing O 0
. O 0

It O 0
differs O 0
from O 0
erythromycin B-Chemical 0
only O 0
in O 0
the O 0
methylation O 0
of O 0
the O 0
hydroxyl O 0
group O 0
at O 0
position O 0
6 O 0
. O 0

Although O 0
the O 0
side O 0
- O 0
effect O 0
profile O 0
of O 0
erythromycin B-Chemical 0
is O 0
established O 0
, O 0
including O 0
gastroenteritis B-Disease 0
and O 0
interactions O 0
with O 0
other O 0
drugs O 0
subject O 0
to O 0
hepatic O 0
mixed O 0
- O 0
function O 0
oxidase O 0
metabolism O 0
, O 0
experience O 0
with O 0
the O 0
newer O 0
macrolides B-Chemical 0
is O 0
still O 0
being O 0
recorded O 0
. O 0

Cardiotoxicity B-Disease 0
has O 0
been O 0
demonstrated O 0
after O 0
both O 0
intravenous O 0
and O 0
oral O 0
administration O 0
of O 0
erythromycin B-Chemical 0
but O 0
has O 0
never O 0
been O 0
reported O 0
with O 0
the O 0
newer O 0
macrolides B-Chemical 0
. O 0

We O 0
report O 0
a O 0
case O 0
of O 0
ventricular B-Disease 0
dysrhythmias I-Disease 0
that O 0
occurred O 0
after O 0
six O 0
therapeutic O 0
doses O 0
of O 0
clarithromycin B-Chemical 0
. O 0

The O 0
dysrhythmias B-Disease 0
resolved O 0
after O 0
discontinuation O 0
of O 0
the O 0
drug O 0
. O 0

Effect O 0
of O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
on O 0
the O 0
sphincter B-Disease 0
of I-Disease 0
Oddi I-Disease 0
spasm I-Disease 0
evoked O 0
by O 0
prostigmine B-Chemical 0
- O 0
morphine B-Chemical 0
administration O 0
. O 0

OBJECTIVE O 0
: O 0
In O 0
this O 0
study O 0
the O 0
effect O 0
of O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
on O 0
the O 0
prostigmine B-Chemical 0
- O 0
morphine B-Chemical 0
- O 0
induced O 0
sphincter B-Disease 0
of I-Disease 0
Oddi I-Disease 0
spasm I-Disease 0
was O 0
evaluated O 0
in O 0
nine O 0
female O 0
patients O 0
with O 0
sphincter B-Disease 0
of I-Disease 0
Oddi I-Disease 0
dyskinesia I-Disease 0
. O 0

METHOD O 0
: O 0
Sphincter B-Disease 0
of I-Disease 0
Oddi I-Disease 0
spasm I-Disease 0
was O 0
induced O 0
by O 0
prostigmine B-Chemical 0
- O 0
morphine B-Chemical 0
administration O 0
( O 0
0 O 0
. O 0
5 O 0
mg O 0
prostigmine B-Chemical 0
intramuscularly O 0
and O 0
10 O 0
mg O 0
morphine B-Chemical 0
subcutaneously O 0
) O 0
and O 0
visualized O 0
by O 0
quantitative O 0
hepatobiliary O 0
scintigraphy O 0
. O 0

The O 0
entire O 0
procedure O 0
was O 0
repeated O 0
during O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
infusion O 0
( O 0
Nitrolingual B-Chemical 0
1 O 0
microg O 0
/ O 0
kg O 0
/ O 0
min O 0
for O 0
120 O 0
min O 0
) O 0
. O 0

RESULTS O 0
: O 0
Prostigmine B-Chemical 0
- O 0
morphine B-Chemical 0
provocation O 0
caused O 0
significant O 0
increases O 0
in O 0
the O 0
time O 0
to O 0
peak O 0
activity O 0
( O 0
Tmax O 0
) O 0
over O 0
the O 0
hepatic O 0
hilum O 0
( O 0
HH O 0
: O 0
34 O 0
. O 0
33 O 0
+ O 0
/ O 0
- O 0
5 O 0
. O 0
05 O 0
vs O 0
. O 0
22 O 0
. O 0
77 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
26 O 0
) O 0
and O 0
the O 0
common O 0
bile O 0
duct O 0
( O 0
CBD O 0
: O 0
60 O 0
. O 0
44 O 0
+ O 0
/ O 0
- O 0
5 O 0
. O 0
99 O 0
vs O 0
. O 0
40 O 0
. O 0
0 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
88 O 0
) O 0
and O 0
in O 0
the O 0
half O 0
- O 0
time O 0
of O 0
excretion O 0
( O 0
T1 O 0
/ O 0
2 O 0
) O 0
over O 0
the O 0
liver O 0
parenchyma O 0
( O 0
LP O 0
: O 0
120 O 0
. O 0
04 O 0
+ O 0
/ O 0
- O 0
16 O 0
. O 0
01 O 0
vs O 0
. O 0
27 O 0
. O 0
37 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
19 O 0
) O 0
, O 0
HH O 0
( O 0
117 O 0
. O 0
61 O 0
+ O 0
/ O 0
- O 0
14 O 0
. O 0
71 O 0
vs O 0
. O 0
31 O 0
. O 0
85 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
99 O 0
) O 0
and O 0
CBD O 0
( O 0
158 O 0
. O 0
11 O 0
+ O 0
/ O 0
- O 0
9 O 0
. O 0
18 O 0
vs O 0
. O 0
40 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
6 O 0
. O 0
24 O 0
) O 0
, O 0
indicating O 0
a O 0
complete O 0
spasm B-Disease 0
at O 0
the O 0
level O 0
of O 0
the O 0
sphincter O 0
of O 0
Oddi O 0
. O 0

Glyceryl B-Chemical 0
trinitrate I-Chemical 0
infusion O 0
completely O 0
normalized O 0
the O 0
prostigmine B-Chemical 0
- O 0
morphine B-Chemical 0
- O 0
induced O 0
alterations O 0
in O 0
these O 0
quantitative O 0
parameters O 0
( O 0
TmaX O 0
over O 0
the O 0
LP O 0
: O 0
11 O 0
. O 0
33 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
13 O 0
; O 0
over O 0
the O 0
HH O 0
: O 0
18 O 0
. O 0
88 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
48 O 0
; O 0
and O 0
over O 0
the O 0
CBD O 0
: O 0
36 O 0
. O 0
22 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
92 O 0
; O 0
and O 0
T1 O 0
/ O 0
2 O 0
over O 0
the O 0
LP O 0
: O 0
28 O 0
. O 0
21 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
83 O 0
; O 0
over O 0
the O 0
HH O 0
: O 0
33 O 0
. O 0
42 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
10 O 0
; O 0
and O 0
over O 0
the O 0
CBD O 0
: O 0
41 O 0
. O 0
66 O 0
+ O 0
/ O 0
- O 0
6 O 0
. O 0
33 O 0
) O 0
, O 0
suggesting O 0
an O 0
effective O 0
sphincter O 0
- O 0
relaxing O 0
effect O 0
of O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
. O 0

CONCLUSION O 0
: O 0
These O 0
results O 0
provide O 0
the O 0
first O 0
evidence O 0
of O 0
the O 0
effectiveness O 0
of O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
on O 0
the O 0
morphine B-Chemical 0
- O 0
induced O 0
sphincter B-Disease 0
of I-Disease 0
Oddi I-Disease 0
spasm I-Disease 0
in O 0
humans O 0
. O 0

Since O 0
glyceryl B-Chemical 0
trinitrate I-Chemical 0
is O 0
able O 0
to O 0
overcome O 0
even O 0
the O 0
drastic O 0
effect O 0
of O 0
morphine B-Chemical 0
, O 0
it O 0
might O 0
be O 0
of O 0
relevance O 0
in O 0
the O 0
treatment O 0
of O 0
sphincter B-Disease 0
of I-Disease 0
Oddi I-Disease 0
dyskinesia I-Disease 0
. O 0

Immunopathology O 0
of O 0
penicillamine B-Chemical 0
- O 0
induced O 0
glomerular B-Disease 0
disease I-Disease 0
. O 0

Four O 0
patients O 0
with O 0
rheumatoid B-Disease 0
arthritis I-Disease 0
developed O 0
heavy O 0
proteinuria B-Disease 0
after O 0
five O 0
to O 0
12 O 0
months O 0
of O 0
treatment O 0
with O 0
D B-Chemical 0
- I-Chemical 0
penicillamine I-Chemical 0
. O 0

Light O 0
microscopy O 0
of O 0
renal O 0
biopsy O 0
samples O 0
showed O 0
minimal O 0
glomerular O 0
capillary O 0
wall O 0
thickening O 0
and O 0
mesangial O 0
matrix O 0
increase O 0
, O 0
or O 0
no O 0
departure O 0
from O 0
normal O 0
. O 0

Electron O 0
microscopy O 0
, O 0
however O 0
, O 0
revealed O 0
subepithelial O 0
electron O 0
- O 0
dense O 0
deposits O 0
, O 0
fusion O 0
of O 0
epithelial O 0
cell O 0
foot O 0
processes O 0
, O 0
and O 0
evidence O 0
of O 0
mesangial O 0
cell O 0
hyperactivity O 0
. O 0

Immunofluorescence O 0
microscopy O 0
demonstrated O 0
granular O 0
capillary O 0
wall O 0
deposits O 0
of O 0
IgG O 0
and O 0
C3 O 0
. O 0

The O 0
findings O 0
were O 0
similar O 0
to O 0
those O 0
in O 0
early O 0
membranous B-Disease 0
glomerulonephritis I-Disease 0
, O 0
differences O 0
being O 0
observed O 0
however O 0
in O 0
the O 0
results O 0
of O 0
staining O 0
for O 0
the O 0
early O 0
- O 0
acting O 0
complement O 0
components O 0
C1q O 0
and O 0
C4 O 0
. O 0

It O 0
is O 0
tentatively O 0
concluded O 0
that O 0
complement O 0
was O 0
activated O 0
by O 0
the O 0
classical O 0
pathway O 0
. O 0

Experimental O 0
cranial O 0
pain B-Disease 0
elicited O 0
by O 0
capsaicin B-Chemical 0
: O 0
a O 0
PET O 0
study O 0
. O 0

Using O 0
a O 0
positron O 0
emission O 0
tomography O 0
( O 0
PET O 0
) O 0
study O 0
it O 0
was O 0
shown O 0
recently O 0
that O 0
in O 0
migraine B-Disease 0
without O 0
aura O 0
certain O 0
areas O 0
in O 0
the O 0
brain O 0
stem O 0
were O 0
activated O 0
during O 0
the O 0
headache B-Disease 0
state O 0
, O 0
but O 0
not O 0
in O 0
the O 0
headache B-Disease 0
free O 0
interval O 0
. O 0

It O 0
was O 0
suggested O 0
that O 0
this O 0
brain O 0
stem O 0
activation O 0
is O 0
inherent O 0
to O 0
the O 0
migraine B-Disease 0
attack O 0
itself O 0
and O 0
represents O 0
the O 0
so O 0
called O 0
' O 0
migraine B-Disease 0
generator O 0
' O 0
. O 0

To O 0
test O 0
this O 0
hypothesis O 0
we O 0
performed O 0
an O 0
experimental O 0
pain B-Disease 0
study O 0
in O 0
seven O 0
healthy O 0
volunteers O 0
, O 0
using O 0
the O 0
same O 0
positioning O 0
in O 0
the O 0
PET O 0
scanner O 0
as O 0
in O 0
the O 0
migraine B-Disease 0
patients O 0
. O 0

A O 0
small O 0
amount O 0
of O 0
capsaicin B-Chemical 0
was O 0
administered O 0
subcutaneously O 0
in O 0
the O 0
right O 0
forehead O 0
to O 0
evoke O 0
a O 0
burning O 0
painful B-Disease 0
sensation O 0
in O 0
the O 0
first O 0
division O 0
of O 0
the O 0
trigeminal O 0
nerve O 0
. O 0

Increases O 0
of O 0
regional O 0
cerebral O 0
blood O 0
flow O 0
( O 0
rCBF O 0
) O 0
were O 0
found O 0
bilaterally O 0
in O 0
the O 0
insula O 0
, O 0
in O 0
the O 0
anterior O 0
cingulate O 0
cortex O 0
, O 0
the O 0
cavernous O 0
sinus O 0
and O 0
the O 0
cerebellum O 0
. O 0

Using O 0
the O 0
same O 0
stereotactic O 0
space O 0
limits O 0
as O 0
in O 0
the O 0
above O 0
mentioned O 0
migraine B-Disease 0
study O 0
no O 0
brain O 0
stem O 0
activation O 0
was O 0
found O 0
in O 0
the O 0
acute O 0
pain B-Disease 0
state O 0
compared O 0
to O 0
the O 0
pain B-Disease 0
free O 0
state O 0
. O 0

The O 0
increase O 0
of O 0
activation O 0
in O 0
the O 0
region O 0
of O 0
the O 0
cavernous O 0
sinus O 0
however O 0
, O 0
suggests O 0
that O 0
this O 0
structure O 0
is O 0
more O 0
likely O 0
to O 0
be O 0
involved O 0
in O 0
trigeminal O 0
transmitted O 0
pain B-Disease 0
as O 0
such O 0
, O 0
rather O 0
than O 0
in O 0
a O 0
specific O 0
type O 0
of O 0
headache B-Disease 0
as O 0
was O 0
suggested O 0
for O 0
cluster B-Disease 0
headache I-Disease 0
. O 0

Value O 0
of O 0
methylprednisolone B-Chemical 0
in O 0
prevention O 0
of O 0
the O 0
arthralgia B-Disease 0
- O 0
myalgia B-Disease 0
syndrome O 0
associated O 0
with O 0
the O 0
total O 0
dose O 0
infusion O 0
of O 0
iron B-Chemical 0
dextran I-Chemical 0
: O 0
a O 0
double O 0
blind O 0
randomized O 0
trial O 0
. O 0

The O 0
safety O 0
and O 0
efficacy O 0
of O 0
total O 0
dose O 0
infusion O 0
( O 0
TDI O 0
) O 0
of O 0
iron B-Chemical 0
dextran I-Chemical 0
has O 0
been O 0
well O 0
documented O 0
. O 0

In O 0
40 O 0
% O 0
of O 0
treated O 0
patients O 0
, O 0
an O 0
arthralgia B-Disease 0
- O 0
myalgia B-Disease 0
syndrome O 0
develops O 0
. O 0

The O 0
purpose O 0
of O 0
this O 0
randomized O 0
, O 0
double O 0
- O 0
blind O 0
, O 0
prospective O 0
study O 0
was O 0
to O 0
investigate O 0
whether O 0
intravenous O 0
( O 0
i O 0
. O 0
v O 0
. O 0
) O 0
administration O 0
of O 0
methylprednisolone B-Chemical 0
( O 0
MP B-Chemical 0
) O 0
prevents O 0
this O 0
complication O 0
. O 0

Sixty O 0
- O 0
five O 0
patients O 0
, O 0
34 O 0
women O 0
and O 0
31 O 0
men O 0
, O 0
ages O 0
36 O 0
to O 0
80 O 0
years O 0
, O 0
received O 0
either O 0
normal O 0
saline O 0
before O 0
and O 0
after O 0
TDI O 0
( O 0
group O 0
1 O 0
) O 0
, O 0
125 O 0
mg O 0
i O 0
. O 0
v O 0
. O 0
MP B-Chemical 0
before O 0
and O 0
saline O 0
after O 0
TDI O 0
( O 0
group O 0
2 O 0
) O 0
, O 0
or O 0
125 O 0
mg O 0
i O 0
. O 0
v O 0
. O 0
MP B-Chemical 0
before O 0
and O 0
after O 0
TDI O 0
( O 0
group O 0
3 O 0
) O 0
. O 0

Patients O 0
were O 0
observed O 0
for O 0
72 O 0
hours O 0
and O 0
reactions O 0
were O 0
recorded O 0
and O 0
graded O 0
according O 0
to O 0
severity O 0
. O 0

Fifty O 0
- O 0
eight O 0
percent O 0
of O 0
group O 0
1 O 0
patients O 0
, O 0
33 O 0
% O 0
of O 0
group O 0
2 O 0
, O 0
and O 0
26 O 0
% O 0
of O 0
group O 0
3 O 0
had O 0
reactions O 0
to O 0
TDI O 0
. O 0

The O 0
severity O 0
of O 0
reactions O 0
( O 0
minimal O 0
, O 0
mild O 0
, O 0
and O 0
moderate O 0
, O 0
respectively O 0
) O 0
was O 0
as O 0
follows O 0
: O 0
group O 0
1 O 0
- O 0
- O 0
6 O 0
, O 0
6 O 0
, O 0
and O 0
2 O 0
; O 0
group O 0
2 O 0
- O 0
- O 0
1 O 0
, O 0
5 O 0
, O 0
and O 0
0 O 0
; O 0
group O 0
3 O 0
- O 0
- O 0
5 O 0
, O 0
1 O 0
, O 0
and O 0
0 O 0
. O 0

Data O 0
were O 0
analyzed O 0
by O 0
the O 0
two O 0
- O 0
sided O 0
Fisher O 0
' O 0
s O 0
exact O 0
test O 0
using O 0
95 O 0
% O 0
confidence O 0
intervals O 0
with O 0
the O 0
approximation O 0
of O 0
Woolf O 0
. O 0

These O 0
data O 0
demonstrate O 0
that O 0
administration O 0
of O 0
MP B-Chemical 0
before O 0
and O 0
after O 0
TDI O 0
reduces O 0
the O 0
frequency O 0
and O 0
severity O 0
of O 0
the O 0
arthralgia B-Disease 0
- O 0
myalgia B-Disease 0
syndrome O 0
. O 0

We O 0
conclude O 0
that O 0
125 O 0
mg O 0
i O 0
. O 0
v O 0
. O 0
MP B-Chemical 0
should O 0
be O 0
given O 0
routinely O 0
before O 0
and O 0
after O 0
TDI O 0
of O 0
iron B-Chemical 0
dextran I-Chemical 0
. O 0

Prolongation B-Disease 0
of I-Disease 0
the I-Disease 0
QT I-Disease 0
interval I-Disease 0
related O 0
to O 0
cisapride B-Chemical 0
- O 0
diltiazem B-Chemical 0
interaction O 0
. O 0

Cisapride B-Chemical 0
, O 0
a O 0
cytochrome O 0
P450 O 0
3A4 O 0
( O 0
CYP3A4 O 0
) O 0
substrate O 0
, O 0
is O 0
widely O 0
prescribed O 0
for O 0
the O 0
treatment O 0
of O 0
gastrointestinal B-Disease 0
motility I-Disease 0
disorders I-Disease 0
. O 0

Prolongation B-Disease 0
of I-Disease 0
QT I-Disease 0
interval I-Disease 0
, O 0
torsades B-Disease 0
de I-Disease 0
pointes I-Disease 0
, O 0
and O 0
sudden B-Disease 0
cardiac I-Disease 0
death I-Disease 0
have O 0
been O 0
reported O 0
after O 0
concomitant O 0
administration O 0
with O 0
erythromycin B-Chemical 0
or O 0
azole B-Chemical 0
antifungal O 0
agents O 0
, O 0
but O 0
not O 0
with O 0
other O 0
CYP3A4 O 0
inhibitors O 0
. O 0

A O 0
possible O 0
drug O 0
interaction O 0
occurred O 0
in O 0
a O 0
45 O 0
- O 0
year O 0
- O 0
old O 0
woman O 0
who O 0
was O 0
taking O 0
cisapride B-Chemical 0
for O 0
gastroesophageal B-Disease 0
reflux I-Disease 0
disorder I-Disease 0
and O 0
diltiazem B-Chemical 0
, O 0
an O 0
agent O 0
that O 0
has O 0
inhibitory O 0
effect O 0
on O 0
CYP3A4 O 0
, O 0
for O 0
hypertension B-Disease 0
. O 0

The O 0
patient O 0
was O 0
in O 0
near O 0
syncope B-Disease 0
and O 0
had O 0
QT B-Disease 0
- I-Disease 0
interval I-Disease 0
prolongation I-Disease 0
. O 0

After O 0
discontinuing O 0
cisapride B-Chemical 0
, O 0
the O 0
QT O 0
interval O 0
returned O 0
to O 0
normal O 0
and O 0
symptoms O 0
did O 0
not O 0
recur O 0
. O 0

We O 0
suggest O 0
that O 0
caution O 0
be O 0
taken O 0
when O 0
cisapride B-Chemical 0
is O 0
prescribed O 0
with O 0
any O 0
potent O 0
inhibitor O 0
of O 0
CYP3A4 O 0
, O 0
including O 0
diltiazem B-Chemical 0
. O 0

Cortical O 0
motor O 0
overactivation O 0
in O 0
parkinsonian B-Disease 0
patients O 0
with O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
- O 0
induced O 0
peak O 0
- O 0
dose O 0
dyskinesia B-Disease 0
. O 0

We O 0
have O 0
studied O 0
the O 0
regional O 0
cerebral O 0
blood O 0
flow O 0
( O 0
rCBF O 0
) O 0
changes O 0
induced O 0
by O 0
the O 0
execution O 0
of O 0
a O 0
finger O 0
- O 0
to O 0
- O 0
thumb O 0
opposition O 0
motor O 0
task O 0
in O 0
the O 0
supplementary O 0
and O 0
primary O 0
motor O 0
cortex O 0
of O 0
two O 0
groups O 0
of O 0
parkinsonian B-Disease 0
patients O 0
on O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
medication O 0
, O 0
the O 0
first O 0
one O 0
without O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
induced O 0
dyskinesia B-Disease 0
( O 0
n O 0
= O 0
23 O 0
) O 0
and O 0
the O 0
other O 0
with O 0
moderate O 0
peak O 0
- O 0
dose O 0
dyskinesia B-Disease 0
( O 0
n O 0
= O 0
15 O 0
) O 0
, O 0
and O 0
of O 0
a O 0
group O 0
of O 0
14 O 0
normal O 0
subjects O 0
. O 0

Single O 0
photon O 0
emission O 0
tomography O 0
with O 0
i O 0
. O 0
v O 0
. O 0
133Xe O 0
was O 0
used O 0
to O 0
measure O 0
the O 0
rCBF O 0
changes O 0
. O 0

The O 0
dyskinetic B-Disease 0
parkinsonian B-Disease 0
patients O 0
exhibited O 0
a O 0
pattern O 0
of O 0
response O 0
which O 0
was O 0
markedly O 0
different O 0
from O 0
those O 0
of O 0
the O 0
normal O 0
subjects O 0
and O 0
non O 0
- O 0
dyskinetic B-Disease 0
parkinsonian B-Disease 0
patients O 0
, O 0
with O 0
a O 0
significant O 0
overactivation O 0
in O 0
the O 0
supplementary O 0
motor O 0
area O 0
and O 0
the O 0
ipsi O 0
- O 0
and O 0
contralateral O 0
primary O 0
motor O 0
areas O 0
. O 0

These O 0
results O 0
are O 0
compatible O 0
with O 0
the O 0
hypothesis O 0
that O 0
an O 0
hyperkinetic B-Disease 0
abnormal B-Disease 0
involuntary I-Disease 0
movement I-Disease 0
, O 0
like O 0
L B-Chemical 0
- I-Chemical 0
dopa I-Chemical 0
- O 0
induced O 0
peak O 0
dose O 0
dyskinesia B-Disease 0
, O 0
is O 0
due O 0
to O 0
a O 0
disinhibition O 0
of O 0
the O 0
primary O 0
and O 0
associated O 0
motor O 0
cortex O 0
secondary O 0
to O 0
an O 0
excessive O 0
outflow O 0
of O 0
the O 0
pallidothalamocortical O 0
motor O 0
loop O 0
. O 0

Open O 0
- O 0
label O 0
assessment O 0
of O 0
levofloxacin B-Chemical 0
for O 0
the O 0
treatment O 0
of O 0
acute O 0
bacterial O 0
sinusitis B-Disease 0
in O 0
adults O 0
. O 0

PURPOSE O 0
: O 0
To O 0
evaluate O 0
the O 0
efficacy O 0
and O 0
safety O 0
of O 0
levofloxacin B-Chemical 0
( O 0
500 O 0
mg O 0
orally O 0
once O 0
daily O 0
for O 0
10 O 0
to O 0
14 O 0
days O 0
) O 0
in O 0
treating O 0
adult O 0
outpatients O 0
with O 0
acute O 0
bacterial O 0
sinusitis B-Disease 0
. O 0

PATIENTS O 0
AND O 0
METHODS O 0
: O 0
A O 0
total O 0
of O 0
329 O 0
patients O 0
enrolled O 0
in O 0
the O 0
study O 0
at O 0
24 O 0
centers O 0
. O 0

All O 0
patients O 0
had O 0
a O 0
pre O 0
- O 0
therapy O 0
Gram O 0
' O 0
s O 0
stain O 0
and O 0
culture O 0
of O 0
sinus O 0
exudate O 0
obtained O 0
by O 0
antral O 0
puncture O 0
or O 0
nasal O 0
endoscopy O 0
. O 0

Clinical O 0
response O 0
was O 0
assessed O 0
on O 0
the O 0
basis O 0
of O 0
signs O 0
and O 0
symptoms O 0
and O 0
sinus O 0
radiograph O 0
or O 0
computed O 0
tomography O 0
results O 0
. O 0

Microbiologic O 0
cure O 0
rates O 0
were O 0
determined O 0
on O 0
the O 0
basis O 0
of O 0
presumed O 0
plus O 0
documented O 0
eradication O 0
of O 0
the O 0
pre O 0
- O 0
therapy O 0
pathogen O 0
( O 0
s O 0
) O 0
. O 0

RESULTS O 0
: O 0
The O 0
most O 0
common O 0
pathogens O 0
were O 0
Haemophilus O 0
influenzae O 0
, O 0
Streptococcus O 0
pneumoniae O 0
, O 0
Staphylococcus O 0
aureus O 0
, O 0
and O 0
Moraxella O 0
catarrhalis O 0
. O 0

Of O 0
300 O 0
clinically O 0
evaluable O 0
patients O 0
, O 0
175 O 0
( O 0
58 O 0
% O 0
) O 0
were O 0
cured O 0
and O 0
90 O 0
( O 0
30 O 0
% O 0
) O 0
were O 0
improved O 0
at O 0
the O 0
post O 0
- O 0
therapy O 0
evaluation O 0
, O 0
resulting O 0
in O 0
a O 0
clinical O 0
success O 0
rate O 0
of O 0
88 O 0
% O 0
. O 0

Thirty O 0
- O 0
five O 0
patients O 0
( O 0
12 O 0
% O 0
) O 0
clinically O 0
failed O 0
treatment O 0
. O 0

The O 0
microbiologic O 0
eradication O 0
rate O 0
( O 0
presumed O 0
plus O 0
documented O 0
) O 0
among O 0
138 O 0
microbiologically O 0
evaluable O 0
patients O 0
was O 0
92 O 0
% O 0
. O 0

Microbiologic O 0
eradication O 0
rates O 0
( O 0
presumed O 0
plus O 0
documented O 0
) O 0
of O 0
the O 0
most O 0
common O 0
pathogens O 0
ranged O 0
from O 0
93 O 0
% O 0
( O 0
M O 0
. O 0
catarrhalis O 0
) O 0
to O 0
100 O 0
% O 0
( O 0
S O 0
. O 0
pneumoniae O 0
) O 0
at O 0
the O 0
post O 0
- O 0
therapy O 0
visit O 0
. O 0

All O 0
but O 0
one O 0
of O 0
the O 0
265 O 0
patients O 0
who O 0
were O 0
cured O 0
or O 0
improved O 0
at O 0
post O 0
- O 0
therapy O 0
returned O 0
for O 0
a O 0
long O 0
- O 0
term O 0
follow O 0
- O 0
up O 0
visit O 0
; O 0
243 O 0
( O 0
92 O 0
% O 0
) O 0
remained O 0
well O 0
4 O 0
to O 0
6 O 0
weeks O 0
after O 0
therapy O 0
; O 0
and O 0
21 O 0
( O 0
8 O 0
% O 0
) O 0
had O 0
a O 0
relapse O 0
of O 0
symptoms O 0
. O 0

Adverse O 0
events O 0
considered O 0
to O 0
be O 0
related O 0
to O 0
levofloxacin B-Chemical 0
administration O 0
were O 0
reported O 0
by O 0
29 O 0
patients O 0
( O 0
9 O 0
% O 0
) O 0
. O 0

The O 0
most O 0
common O 0
drug O 0
- O 0
related O 0
adverse O 0
events O 0
were O 0
diarrhea B-Disease 0
, O 0
flatulence B-Disease 0
, O 0
and O 0
nausea B-Disease 0
; O 0
most O 0
adverse O 0
events O 0
were O 0
mild O 0
to O 0
moderate O 0
in O 0
severity O 0
. O 0

CONCLUSION 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
levofloxacin B-Chemical 0
500 O 0
mg O 0
once O 0
daily O 0
is O 0
an O 0
effective O 0
and O 0
safe O 0
treatment O 0
for O 0
acute O 0
bacterial O 0
sinusitis B-Disease 0
. O 0

Iatrogenic O 0
risks O 0
of O 0
endometrial B-Disease 0
carcinoma I-Disease 0
after O 0
treatment O 0
for O 0
breast B-Disease 0
cancer I-Disease 0
in O 0
a O 0
large O 0
French O 0
case O 0
- O 0
control O 0
study O 0
. O 0

F O 0
d O 0
ration O 0
Nationale O 0
des O 0
Centres O 0
de O 0
Lutte O 0
Contre O 0
le O 0
Cancer O 0
( O 0
FNCLCC O 0
) O 0
. O 0

Since O 0
tamoxifen B-Chemical 0
is O 0
widely O 0
used O 0
in O 0
breast B-Disease 0
cancer I-Disease 0
treatment O 0
and O 0
has O 0
been O 0
proposed O 0
for O 0
the O 0
prevention O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
, O 0
its O 0
endometrial O 0
iatrogenic O 0
effects O 0
must O 0
be O 0
carefully O 0
examined O 0
. O 0

We O 0
have O 0
investigated O 0
the O 0
association O 0
between O 0
endometrial B-Disease 0
cancer I-Disease 0
and O 0
tamoxifen B-Chemical 0
use O 0
or O 0
other O 0
treatments O 0
in O 0
women O 0
treated O 0
for O 0
breast B-Disease 0
cancer I-Disease 0
in O 0
a O 0
case O 0
- O 0
control O 0
study O 0
. O 0

Cases O 0
of O 0
endometrial B-Disease 0
cancer I-Disease 0
diagnosed O 0
after O 0
breast B-Disease 0
cancer I-Disease 0
( O 0
n O 0
= O 0
135 O 0
) O 0
and O 0
467 O 0
controls O 0
matched O 0
for O 0
age O 0
, O 0
year O 0
of O 0
diagnosis O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
and O 0
hospital O 0
and O 0
survival O 0
time O 0
with O 0
an O 0
intact O 0
uterus O 0
were O 0
included O 0
. O 0

Women O 0
who O 0
had O 0
received O 0
tamoxifen B-Chemical 0
were O 0
significantly O 0
more O 0
likely O 0
to O 0
have O 0
endometrial B-Disease 0
cancer I-Disease 0
diagnosed O 0
than O 0
those O 0
who O 0
had O 0
not O 0
( O 0
crude O 0
relative O 0
risk O 0
= O 0
4 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

Univariate O 0
and O 0
adjusted O 0
analyses O 0
showed O 0
that O 0
the O 0
risk O 0
increased O 0
with O 0
the O 0
length O 0
of O 0
treatment O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
0001 O 0
) O 0
or O 0
the O 0
cumulative O 0
dose O 0
of O 0
tamoxifen B-Chemical 0
received O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
0001 O 0
) O 0
, O 0
irrespective O 0
of O 0
the O 0
daily O 0
dose O 0
. O 0

Women O 0
who O 0
had O 0
undergone O 0
pelvic O 0
radiotherapy O 0
also O 0
had O 0
a O 0
higher O 0
risk O 0
( O 0
crude O 0
relative O 0
risk O 0
= O 0
7 O 0
. O 0
8 O 0
, O 0
p O 0
= O 0
0 O 0
. O 0
0001 O 0
) O 0
. O 0

After O 0
adjusting O 0
for O 0
confounding O 0
factors O 0
, O 0
the O 0
risk O 0
was O 0
higher O 0
for O 0
tamoxifen B-Chemical 0
users O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
0012 O 0
) O 0
, O 0
treatment O 0
for O 0
more O 0
than O 0
3 O 0
years O 0
( O 0
all O 0
p O 0
< O 0
0 O 0
. O 0
03 O 0
) O 0
and O 0
pelvic O 0
radiotherapy O 0
( O 0
p O 0
= O 0
0 O 0
. O 0
012 O 0
) O 0
. O 0

Women O 0
who O 0
had O 0
endometrial B-Disease 0
cancer I-Disease 0
and O 0
had O 0
received O 0
tamoxifen B-Chemical 0
had O 0
more O 0
advanced B-Disease 0
disease I-Disease 0
and O 0
poorer O 0
prognosis O 0
than O 0
those O 0
with O 0
endometrial B-Disease 0
cancer I-Disease 0
who O 0
had O 0
not O 0
received O 0
this O 0
treatment O 0
. O 0

Our O 0
results O 0
suggest O 0
a O 0
causal O 0
role O 0
of O 0
tamoxifen B-Chemical 0
in O 0
endometrial B-Disease 0
cancer I-Disease 0
, O 0
particularly O 0
when O 0
used O 0
as O 0
currently O 0
proposed O 0
for O 0
breast B-Disease 0
cancer I-Disease 0
prevention O 0
. O 0

Pelvic O 0
radiotherapy O 0
may O 0
be O 0
an O 0
additional O 0
iatrogenic O 0
factor O 0
for O 0
women O 0
with O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

Endometrial B-Disease 0
cancers I-Disease 0
diagnosed O 0
in O 0
women O 0
treated O 0
with O 0
tamoxifen B-Chemical 0
have O 0
poorer O 0
prognosis O 0
. O 0

Women O 0
who O 0
receive O 0
tamoxifen B-Chemical 0
for O 0
breast B-Disease 0
cancer I-Disease 0
should O 0
be O 0
offered O 0
gynaecological O 0
surveillance O 0
during O 0
and O 0
after O 0
treatment O 0
. O 0

A O 0
long O 0
- O 0
term O 0
evaluation O 0
of O 0
the O 0
risk O 0
- O 0
benefit O 0
ratio O 0
of O 0
tamoxifen B-Chemical 0
as O 0
a O 0
preventive O 0
treatment O 0
for O 0
breast B-Disease 0
cancer I-Disease 0
is O 0
clearly O 0
warranted O 0
. O 0

Contribution O 0
of O 0
the O 0
glycine B-Chemical 0
site O 0
of O 0
NMDA B-Chemical 0
receptors O 0
in O 0
rostral O 0
and O 0
intermediate O 0
- O 0
caudal O 0
parts O 0
of O 0
the O 0
striatum O 0
to O 0
the O 0
regulation O 0
of O 0
muscle O 0
tone O 0
in O 0
rats 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
assess O 0
the O 0
contribution O 0
of O 0
the O 0
glycine B-Chemical 0
site O 0
of O 0
NMDA B-Chemical 0
receptors O 0
in O 0
the O 0
striatum O 0
to O 0
the O 0
regulation O 0
of O 0
muscle O 0
tone O 0
. O 0

Muscle O 0
tone O 0
was O 0
examined O 0
using O 0
a O 0
combined O 0
mechanoand O 0
electromyographic O 0
method O 0
, O 0
which O 0
measured O 0
simultaneously O 0
the O 0
muscle O 0
resistance O 0
( O 0
MMG O 0
) O 0
of O 0
the O 0
rat O 0
' O 0
s O 0
hind O 0
foot O 0
to O 0
passive O 0
extension O 0
and O 0
flexion O 0
in O 0
the O 0
ankle O 0
joint O 0
and O 0
the O 0
electromyographic O 0
activity O 0
( O 0
EMG O 0
) O 0
of O 0
the O 0
antagonistic O 0
muscles O 0
of O 0
that O 0
joint O 0
: O 0
gastrocnemius O 0
and O 0
tibialis O 0
anterior O 0
. O 0

Muscle B-Disease 0
rigidity I-Disease 0
was O 0
induced O 0
by O 0
haloperidol B-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
) O 0
. O 0

5 B-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
dichlorokynurenic I-Chemical 0
acid I-Chemical 0
( O 0
5 B-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
DCKA I-Chemical 0
) O 0
, O 0
a O 0
selective O 0
glycine B-Chemical 0
site O 0
antagonist O 0
, O 0
injected O 0
in O 0
doses O 0
of O 0
2 O 0
. O 0
5 O 0
and O 0
4 O 0
. O 0
5 O 0
microg O 0
/ O 0
0 O 0
. O 0
5 O 0
microl O 0
bilaterally O 0
, O 0
into O 0
the O 0
rostral O 0
region O 0
of O 0
the O 0
striatum O 0
, O 0
decreased O 0
both O 0
the O 0
haloperidol B-Chemical 0
- O 0
induced O 0
muscle B-Disease 0
rigidity I-Disease 0
( O 0
MMG O 0
) O 0
and O 0
the O 0
enhanced O 0
electromyographic O 0
activity O 0
( O 0
EMG O 0
) O 0
. O 0

5 B-Chemical 0
, I-Chemical 0
7 I-Chemical 0
- I-Chemical 0
DCKA I-Chemical 0
injected O 0
bilaterally O 0
in O 0
a O 0
dose O 0
of O 0
4 O 0
. O 0
5 O 0
microg O 0
/ O 0
0 O 0
. O 0
5 O 0
microl O 0
into O 0
the O 0
intermediate O 0
- O 0
caudal O 0
region O 0
of O 0
the O 0
striatum O 0
of O 0
rats O 0
not O 0
pretreated O 0
with O 0
haloperidol B-Chemical 0
had O 0
no O 0
effect O 0
on O 0
the O 0
muscle O 0
tone O 0
. O 0

The O 0
present O 0
results O 0
suggest O 0
that O 0
blockade O 0
of O 0
the O 0
glycine B-Chemical 0
site O 0
of O 0
NMDA B-Chemical 0
receptors O 0
in O 0
the O 0
rostral O 0
part O 0
of O 0
the O 0
striatum O 0
may O 0
be O 0
mainly O 0
responsible O 0
for O 0
the O 0
antiparkinsonian O 0
action O 0
of O 0
this O 0
drug O 0
. O 0

Carboplatin B-Chemical 0
toxic O 0
effects O 0
on O 0
the O 0
peripheral O 0
nervous O 0
system O 0
of O 0
the O 0
rat O 0
. O 0

BACKGROUND O 0
: O 0
The O 0
most O 0
striking O 0
of O 0
carboplatin B-Chemical 0
' O 0
s O 0
advantages O 0
( O 0
CBDCA B-Chemical 0
) O 0
over O 0
cisplatin B-Chemical 0
( O 0
CDDP B-Chemical 0
) O 0
is O 0
its O 0
markedly O 0
reduced O 0
rate O 0
of O 0
neurotoxic B-Disease 0
effects O 0
. O 0

However O 0
, O 0
the O 0
use O 0
of O 0
CBDCA B-Chemical 0
higher O 0
- O 0
intensity O 0
schedules O 0
and O 0
the O 0
association O 0
with O 0
other O 0
neurotoxic B-Disease 0
drugs O 0
in O 0
polychemotherapy O 0
may O 0
cause O 0
some O 0
concern O 0
about O 0
its O 0
safety O 0
with O 0
respect O 0
to O 0
peripheral B-Disease 0
nervous I-Disease 0
system I-Disease 0
damage I-Disease 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
Two O 0
different O 0
schedules O 0
of O 0
CBDCA B-Chemical 0
administration O 0
( O 0
10 O 0
mg O 0
/ O 0
kg O 0
and O 0
15 O 0
mg O 0
/ O 0
kg O 0
i O 0
. O 0
p O 0
. O 0
twice O 0
a O 0
week O 0
for O 0
nine O 0
times O 0
) O 0
were O 0
evaluated O 0
in O 0
Wistar O 0
rats O 0
. O 0

Neurotoxicity B-Disease 0
was O 0
assessed O 0
for O 0
behavioral O 0
( O 0
tail O 0
- O 0
flick O 0
test O 0
) O 0
, O 0
neurophysiological O 0
( O 0
nerve O 0
conduction O 0
velocity O 0
in O 0
the O 0
tail O 0
nerve O 0
) O 0
, O 0
morphological O 0
, O 0
morphometrical O 0
and O 0
analytical O 0
effects O 0
. O 0

RESULTS O 0
: O 0
CBDCA B-Chemical 0
administration O 0
induced O 0
dose O 0
- O 0
dependent O 0
peripheral B-Disease 0
neurotoxicity I-Disease 0
. O 0

Pain B-Disease 0
perception O 0
and O 0
nerve O 0
conduction O 0
velocity O 0
in O 0
the O 0
tail O 0
were O 0
significantly O 0
impaired O 0
, O 0
particularly O 0
after O 0
the O 0
high O 0
- O 0
dose O 0
treatment O 0
. O 0

The O 0
dorsal O 0
root O 0
ganglia O 0
sensory O 0
neurons O 0
and O 0
, O 0
to O 0
a O 0
lesser O 0
extent O 0
, O 0
satellite O 0
cells O 0
showed O 0
the O 0
same O 0
changes O 0
as O 0
those O 0
induced O 0
by O 0
CDDP B-Chemical 0
, O 0
mainly O 0
affecting O 0
the O 0
nucleus O 0
and O 0
nucleolus O 0
of O 0
ganglionic O 0
sensory O 0
neurons O 0
. O 0

Moreover O 0
, O 0
significant O 0
amounts O 0
of O 0
platinum B-Chemical 0
were O 0
detected O 0
in O 0
the O 0
dorsal O 0
root O 0
ganglia O 0
and O 0
kidney O 0
after O 0
CBDCA B-Chemical 0
treatment O 0
. O 0

CONCLUSIONS O 0
: O 0
CBDCA B-Chemical 0
is O 0
neurotoxic B-Disease 0
in O 0
our O 0
model O 0
, O 0
and O 0
the O 0
type O 0
of O 0
pathological O 0
changes O 0
it O 0
induces O 0
are O 0
so O 0
closely O 0
similar O 0
to O 0
those O 0
caused O 0
by O 0
CDDP B-Chemical 0
that O 0
it O 0
is O 0
probable O 0
that O 0
neurotoxicity B-Disease 0
is O 0
induced O 0
in O 0
the O 0
two O 0
drugs O 0
by O 0
the O 0
same O 0
mechanism O 0
. O 0

This O 0
model O 0
can O 0
be O 0
used O 0
alone O 0
or O 0
in O 0
combination O 0
with O 0
other O 0
drugs O 0
to O 0
explore O 0
the O 0
effect O 0
of O 0
CBDCA B-Chemical 0
on O 0
the O 0
peripheral O 0
nervous O 0
system O 0
. O 0

Effects O 0
of O 0
cisapride B-Chemical 0
on O 0
symptoms O 0
and O 0
postcibal O 0
small O 0
- O 0
bowel O 0
motor O 0
function O 0
in O 0
patients O 0
with O 0
irritable B-Disease 0
bowel I-Disease 0
syndrome I-Disease 0
. O 0

BACKGROUND O 0
: O 0
Irritable B-Disease 0
bowel I-Disease 0
syndrome I-Disease 0
is O 0
a O 0
common O 0
cause O 0
of O 0
abdominal B-Disease 0
pain I-Disease 0
and O 0
discomfort O 0
and O 0
may O 0
be O 0
related O 0
to O 0
disordered B-Disease 0
gastrointestinal I-Disease 0
motility I-Disease 0
. O 0

Our O 0
aim O 0
was O 0
to O 0
assess O 0
the O 0
effects O 0
of O 0
long O 0
- O 0
term O 0
treatment O 0
with O 0
a O 0
prokinetic O 0
agent O 0
, O 0
cisapride B-Chemical 0
, O 0
on O 0
postprandial O 0
jejunal O 0
motility O 0
and O 0
symptoms O 0
in O 0
the O 0
irritable B-Disease 0
bowel I-Disease 0
syndrome I-Disease 0
( O 0
IBS B-Disease 0
) O 0
. O 0

METHODS O 0
: O 0
Thirty O 0
- O 0
eight O 0
patients O 0
with O 0
IBS B-Disease 0
( O 0
constipation B-Disease 0
- O 0
predominant O 0
, O 0
n O 0
= O 0
17 O 0
; O 0
diarrhoea B-Disease 0
- O 0
predominant O 0
, O 0
n O 0
= O 0
21 O 0
) O 0
underwent O 0
24 O 0
- O 0
h O 0
ambulatory O 0
jejunal O 0
manometry O 0
before O 0
and O 0
after O 0
12 O 0
week O 0
' O 0
s O 0
treatment O 0
[ O 0
cisapride B-Chemical 0
, O 0
5 O 0
mg O 0
three O 0
times O 0
daily O 0
( O 0
n O 0
= O 0
19 O 0
) O 0
or O 0
placebo O 0
( O 0
n O 0
= O 0
19 O 0
) O 0
] O 0
. O 0

RESULTS O 0
: O 0
In O 0
diarrhoea B-Disease 0
- O 0
predominant O 0
patients O 0
significant O 0
differences O 0
in O 0
contraction O 0
characteristics O 0
were O 0
observed O 0
between O 0
the O 0
cisapride B-Chemical 0
and O 0
placebo O 0
groups O 0
. O 0

In O 0
cisapride B-Chemical 0
- O 0
treated O 0
diarrhoea B-Disease 0
- O 0
predominant O 0
patients O 0
the O 0
mean O 0
contraction O 0
amplitude O 0
was O 0
higher O 0
( O 0
29 O 0
. O 0
3 O 0
+ O 0
/ O 0
- O 0
3 O 0
. O 0
2 O 0
versus O 0
24 O 0
. O 0
9 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
6 O 0
mm O 0
Hg O 0
, O 0
cisapride B-Chemical 0
versus O 0
placebo O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
; O 0
pretreatment O 0
, O 0
25 O 0
. O 0
7 O 0
+ O 0
/ O 0
- O 0
6 O 0
. O 0
0 O 0
mm O 0
Hg O 0
) O 0
, O 0
the O 0
mean O 0
contraction O 0
duration O 0
longer O 0
( O 0
3 O 0
. O 0
4 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
versus O 0
3 O 0
. O 0
0 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
sec O 0
, O 0
cisapride B-Chemical 0
versus O 0
placebo O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
; O 0
pretreatment O 0
, O 0
3 O 0
. O 0
1 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
5 O 0
sec O 0
) O 0
, O 0
and O 0
the O 0
mean O 0
contraction O 0
frequency O 0
lower O 0
( O 0
2 O 0
. O 0
0 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
2 O 0
versus O 0
2 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
4 O 0
cont O 0
. O 0
/ O 0
min O 0
, O 0
cisapride B-Chemical 0
versus O 0
placebo O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
001 O 0
) O 0
; O 0
pretreatment O 0
, O 0
2 O 0
. O 0
5 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
1 O 0
cont O 0
. O 0
/ O 0
min O 0
] O 0
than O 0
patients O 0
treated O 0
with O 0
placebo O 0
. O 0

No O 0
significant O 0
differences O 0
in O 0
jejunal O 0
motility O 0
were O 0
found O 0
in O 0
the O 0
constipation B-Disease 0
- O 0
predominant O 0
IBS B-Disease 0
group O 0
. O 0

Symptoms O 0
were O 0
assessed O 0
by O 0
using O 0
a O 0
visual O 0
analogue O 0
scale O 0
before O 0
and O 0
after O 0
treatment O 0
. O 0

Symptom O 0
scores O 0
relating O 0
to O 0
the O 0
severity O 0
of O 0
constipation B-Disease 0
were O 0
lower O 0
in O 0
cisapride B-Chemical 0
- O 0
treated O 0
constipation B-Disease 0
- O 0
predominant O 0
IBS B-Disease 0
patients O 0
[ O 0
score O 0
, O 0
54 O 0
+ O 0
/ O 0
- O 0
5 O 0
versus O 0
67 O 0
+ O 0
/ O 0
- O 0
14 O 0
mm O 0
, O 0
cisapride B-Chemical 0
versus O 0
placebo O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
; O 0
pretreatment O 0
, O 0
62 O 0
+ O 0
/ O 0
- O 0
19 O 0
mm O 0
] O 0
. O 0

Diarrhoea B-Disease 0
- O 0
predominant O 0
IBS B-Disease 0
patients O 0
had O 0
a O 0
higher O 0
pain B-Disease 0
score O 0
after O 0
cisapride B-Chemical 0
therapy O 0
[ O 0
score O 0
, O 0
55 O 0
+ O 0
/ O 0
- O 0
15 O 0
versus O 0
34 O 0
+ O 0
/ O 0
- O 0
12 O 0
mm O 0
, O 0
cisapride B-Chemical 0
versus O 0
placebo O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
05 O 0
) O 0
; O 0
pretreatment O 0
, O 0
67 O 0
+ O 0
/ O 0
- O 0
19 O 0
mm O 0
] O 0
. O 0

CONCLUSION O 0
: O 0
Cisapride B-Chemical 0
affects O 0
jejunal O 0
contraction O 0
characteristics O 0
and O 0
some O 0
symptoms O 0
in O 0
IBS B-Disease 0
. O 0

Prevention O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
with O 0
tamoxifen B-Chemical 0
: O 0
preliminary O 0
findings O 0
from O 0
the O 0
Italian O 0
randomised O 0
trial O 0
among O 0
hysterectomised O 0
women O 0
. O 0

Italian O 0
Tamoxifen B-Chemical 0
Prevention O 0
Study O 0
. O 0

BACKGROUND O 0
: O 0
Tamoxifen B-Chemical 0
is O 0
a O 0
candidate O 0
chemopreventive O 0
agent O 0
in O 0
breast B-Disease 0
cancer I-Disease 0
, O 0
although O 0
the O 0
drug O 0
may O 0
be O 0
associated O 0
with O 0
the O 0
development O 0
of O 0
endometrial B-Disease 0
cancer I-Disease 0
. O 0

Therefore O 0
we O 0
did O 0
a O 0
trial O 0
in O 0
hysterectomised O 0
women O 0
of O 0
tamoxifen B-Chemical 0
as O 0
a O 0
chemopreventive O 0
. O 0

METHODS O 0
: O 0
In O 0
October O 0
, O 0
1992 O 0
, O 0
we O 0
started O 0
a O 0
double O 0
- O 0
blind O 0
placebo O 0
- O 0
controlled O 0
, O 0
randomised O 0
trial O 0
of O 0
tamoxifen B-Chemical 0
in O 0
women O 0
( O 0
mainly O 0
in O 0
Italy O 0
) O 0
who O 0
did O 0
not O 0
have O 0
breast B-Disease 0
cancer I-Disease 0
and O 0
who O 0
had O 0
had O 0
a O 0
hysterectomy O 0
. O 0

Women O 0
were O 0
randomised O 0
to O 0
receive O 0
tamoxifen B-Chemical 0
20 O 0
mg O 0
per O 0
day O 0
or O 0
placebo O 0
, O 0
both O 0
orally O 0
for O 0
5 O 0
years O 0
. O 0

The O 0
original O 0
plan O 0
was O 0
to O 0
follow O 0
the O 0
intervention O 0
phase O 0
by O 0
5 O 0
years O 0
' O 0
follow O 0
- O 0
up O 0
. O 0

In O 0
June O 0
, O 0
1997 O 0
, O 0
the O 0
trialists O 0
and O 0
the O 0
data O 0
- O 0
monitoring O 0
committee O 0
decided O 0
to O 0
end O 0
recruitment O 0
primarily O 0
because O 0
of O 0
the O 0
number O 0
of O 0
women O 0
dropping O 0
out O 0
of O 0
the O 0
study O 0
. O 0

Recruitment O 0
ended O 0
on O 0
July O 0
11 O 0
, O 0
1997 O 0
, O 0
and O 0
the O 0
study O 0
will O 0
continue O 0
as O 0
planned O 0
. O 0

The O 0
primary O 0
endpoints O 0
are O 0
the O 0
occurrence O 0
of O 0
and O 0
deaths O 0
from O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

This O 0
preliminary O 0
interim O 0
analysis O 0
is O 0
based O 0
on O 0
intention O 0
- O 0
to O 0
- O 0
treat O 0
. O 0

FINDINGS O 0
: O 0
5408 O 0
women O 0
were O 0
randomised O 0
; O 0
participating O 0
women O 0
have O 0
a O 0
median O 0
follow O 0
- O 0
up O 0
of O 0
46 O 0
months O 0
for O 0
major O 0
endpoints O 0
. O 0

41 O 0
cases O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
occurred O 0
so O 0
far O 0
; O 0
there O 0
have O 0
been O 0
no O 0
deaths O 0
from O 0
breast B-Disease 0
cancer I-Disease 0
. O 0

There O 0
is O 0
no O 0
difference O 0
in O 0
breast B-Disease 0
- I-Disease 0
cancer I-Disease 0
frequency O 0
between O 0
the O 0
placebo O 0
( O 0
22 O 0
cases O 0
) O 0
and O 0
tamoxifen B-Chemical 0
( O 0
19 O 0
) O 0
arms O 0
. O 0

There O 0
is O 0
a O 0
statistically O 0
significant O 0
reduction O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
among O 0
women O 0
receiving O 0
tamoxifen B-Chemical 0
who O 0
also O 0
used O 0
hormone O 0
- O 0
replacement O 0
therapy O 0
during O 0
the O 0
trial O 0
: O 0
among O 0
390 O 0
women O 0
on O 0
such O 0
therapy O 0
and O 0
allocated O 0
to O 0
placebo O 0
, O 0
we O 0
found O 0
eight O 0
cases O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
compared O 0
with O 0
one O 0
case O 0
among O 0
362 O 0
women O 0
allocated O 0
to O 0
tamoxifen B-Chemical 0
. O 0

Compared O 0
with O 0
the O 0
placebo O 0
group O 0
, O 0
there O 0
was O 0
a O 0
significantly O 0
increased O 0
risk O 0
of O 0
vascular B-Disease 0
events I-Disease 0
and O 0
hypertriglyceridaemia B-Disease 0
among O 0
women O 0
on O 0
tamoxifen B-Chemical 0
. O 0

INTERPRETATION O 0
: O 0
Although O 0
this O 0
preliminary O 0
analysis O 0
has O 0
low O 0
power O 0
, O 0
in O 0
this O 0
cohort O 0
of O 0
women O 0
at O 0
low O 0
- O 0
to O 0
- O 0
normal O 0
risk O 0
of O 0
breast B-Disease 0
cancer I-Disease 0
, O 0
the O 0
postulated O 0
protective O 0
effects O 0
of O 0
tamoxifen B-Chemical 0
are O 0
not O 0
yet O 0
apparent O 0
. O 0

Women O 0
using O 0
hormone O 0
- O 0
replacement O 0
therapy O 0
appear O 0
to O 0
have O 0
benefited O 0
from O 0
use O 0
of O 0
tamoxifen B-Chemical 0
. O 0

There O 0
were O 0
no O 0
deaths O 0
from O 0
breast B-Disease 0
cancer I-Disease 0
recorded O 0
in O 0
women O 0
in O 0
the O 0
study O 0
. O 0

It O 0
is O 0
essential O 0
to O 0
continue O 0
follow O 0
- O 0
up O 0
to O 0
quantify O 0
the O 0
long O 0
- O 0
term O 0
risks O 0
and O 0
benefits O 0
of O 0
tamoxifen B-Chemical 0
therapy O 0
. O 0

Epileptogenic O 0
activity O 0
of O 0
folic B-Chemical 0
acid I-Chemical 0
after O 0
drug O 0
induces O 0
SLE B-Disease 0
( O 0
folic B-Chemical 0
acid I-Chemical 0
and O 0
epilepsy B-Disease 0
) O 0

OBJECTIVE O 0
: O 0
To O 0
study O 0
the O 0
effect O 0
of O 0
folic B-Chemical 0
acid I-Chemical 0
- O 0
containing O 0
multivitamin O 0
supplementation O 0
in O 0
epileptic B-Disease 0
women O 0
before O 0
and O 0
during O 0
pregnancy O 0
in O 0
order O 0
to O 0
determine O 0
the O 0
rate O 0
of O 0
structural O 0
birth B-Disease 0
defects I-Disease 0
and O 0
epilepsy B-Disease 0
- O 0
related O 0
side O 0
effects O 0
. O 0

STUDY O 0
DESIGN O 0
: O 0
First O 0
a O 0
randomised O 0
trial O 0
, O 0
later O 0
periconception O 0
care O 0
including O 0
in O 0
total O 0
12225 O 0
females O 0
. O 0

RESULTS O 0
: O 0
Of O 0
60 O 0
epileptic B-Disease 0
women O 0
with O 0
periconceptional O 0
folic B-Chemical 0
acid I-Chemical 0
( O 0
0 O 0
. O 0
8 O 0
mg O 0
) O 0
- O 0
containing O 0
multivitamin O 0
supplementation O 0
, O 0
no O 0
one O 0
developed O 0
epilepsy B-Disease 0
- O 0
related O 0
side O 0
effects O 0
during O 0
the O 0
periconception O 0
period O 0
. O 0

One O 0
epileptic B-Disease 0
woman O 0
delivered O 0
a O 0
newborn O 0
with O 0
cleft B-Disease 0
lip I-Disease 0
and I-Disease 0
palate I-Disease 0
. O 0

Another O 0
patient O 0
exhibited O 0
with O 0
a O 0
cluster O 0
of O 0
seizures B-Disease 0
after O 0
the O 0
periconception O 0
period O 0
using O 0
another O 0
multivitamin O 0
. O 0

This O 0
22 O 0
- O 0
year O 0
- O 0
old O 0
epileptic B-Disease 0
woman O 0
was O 0
treated O 0
continuously O 0
by O 0
carbamazepine B-Chemical 0
and O 0
a O 0
folic B-Chemical 0
acid I-Chemical 0
( O 0
1 O 0
mg O 0
) O 0
- O 0
containing O 0
multivitamin O 0
from O 0
the O 0
20th O 0
week O 0
of O 0
gestation O 0
. O 0

She O 0
developed O 0
status B-Disease 0
epilepticus I-Disease 0
and O 0
later O 0
symptoms O 0
of O 0
systemic B-Disease 0
lupus I-Disease 0
erythematodes I-Disease 0
. O 0

Her O 0
pregnancy O 0
ended O 0
with O 0
stillbirth B-Disease 0
. O 0

CONCLUSIONS O 0
: O 0
The O 0
epileptic B-Disease 0
pregnant O 0
patient O 0
' O 0
s O 0
autoimmune B-Disease 0
disease I-Disease 0
( O 0
probably O 0
drug O 0
- O 0
induced O 0
lupus B-Disease 0
) O 0
could O 0
damage O 0
the O 0
blood O 0
- O 0
brain O 0
barrier O 0
, O 0
therefore O 0
the O 0
therapeutic O 0
dose O 0
( O 0
> O 0
or O 0
= O 0
1 O 0
mg O 0
) O 0
of O 0
folic B-Chemical 0
acid I-Chemical 0
triggered O 0
a O 0
cluster O 0
of O 0
seizures B-Disease 0
. O 0

Physiological O 0
dose O 0
( O 0
< O 0
1 O 0
mg O 0
) O 0
of O 0
folic B-Chemical 0
acid I-Chemical 0
both O 0
in O 0
healthy O 0
and O 0
60 O 0
epileptic B-Disease 0
women O 0
, O 0
all O 0
without O 0
any O 0
autoimmune B-Disease 0
disease I-Disease 0
, O 0
did O 0
not O 0
increase O 0
the O 0
risk O 0
for O 0
epileptic B-Disease 0
seizures I-Disease 0
. O 0

Stroke B-Disease 0
and O 0
cocaine B-Chemical 0
or O 0
amphetamine B-Chemical 0
use O 0
. O 0

The O 0
association O 0
of O 0
cocaine B-Chemical 0
and O 0
amphetamine B-Chemical 0
use O 0
with O 0
hemorrhagic O 0
and O 0
ischemic B-Disease 0
stroke B-Disease 0
is O 0
based O 0
almost O 0
solely O 0
on O 0
data O 0
from O 0
case O 0
series O 0
. O 0

The O 0
limited O 0
number O 0
of O 0
epidemiologic O 0
studies O 0
of O 0
stroke B-Disease 0
and O 0
use O 0
of O 0
cocaine B-Chemical 0
and O 0
/ O 0
or O 0
amphetamine B-Chemical 0
have O 0
been O 0
done O 0
in O 0
settings O 0
that O 0
serve O 0
mostly O 0
the O 0
poor O 0
and O 0
/ O 0
or O 0
minorities O 0
. O 0

This O 0
case O 0
- O 0
control O 0
study O 0
was O 0
conducted O 0
in O 0
the O 0
defined O 0
population O 0
comprising O 0
members O 0
of O 0
Kaiser O 0
Permanente O 0
of O 0
Northern O 0
and O 0
Southern O 0
California O 0
. O 0

We O 0
attempted O 0
to O 0
identify O 0
all O 0
incident O 0
strokes B-Disease 0
in O 0
women O 0
ages O 0
15 O 0
- O 0
44 O 0
years O 0
during O 0
a O 0
3 O 0
- O 0
year O 0
period O 0
using O 0
hospital O 0
admission O 0
and O 0
discharge O 0
records O 0
, O 0
emergency O 0
department O 0
logs O 0
, O 0
and O 0
payment O 0
requests O 0
for O 0
out O 0
- O 0
of O 0
- O 0
plan O 0
hospitalizations O 0
. O 0

We O 0
selected O 0
controls O 0
, O 0
matched O 0
on O 0
age O 0
and O 0
facility O 0
of O 0
usual O 0
care O 0
, O 0
at O 0
random O 0
from O 0
healthy O 0
members O 0
of O 0
the O 0
health O 0
plan O 0
. O 0

We O 0
obtained O 0
information O 0
in O 0
face O 0
- O 0
to O 0
- O 0
face O 0
interviews O 0
. O 0

There O 0
were O 0
347 O 0
confirmed O 0
stroke B-Disease 0
cases O 0
and O 0
1 O 0
, O 0
021 O 0
controls O 0
. O 0

The O 0
univariate O 0
matched O 0
odds O 0
ratio O 0
for O 0
stroke B-Disease 0
in O 0
women O 0
who O 0
admitted O 0
to O 0
using O 0
cocaine B-Chemical 0
and O 0
/ O 0
or O 0
amphetamine B-Chemical 0
was O 0
8 O 0
. O 0
5 O 0
( O 0
95 O 0
% O 0
confidence O 0
interval O 0
= O 0
3 O 0
. O 0
6 O 0
- O 0
20 O 0
. O 0
0 O 0
) O 0
. O 0

After O 0
further O 0
adjustment O 0
for O 0
potential O 0
confounders O 0
, O 0
the O 0
odds O 0
ratio O 0
in O 0
women O 0
who O 0
reported O 0
using O 0
cocaine B-Chemical 0
and O 0
/ O 0
or O 0
amphetamine B-Chemical 0
was O 0
7 O 0
. O 0
0 O 0
( O 0
95 O 0
% O 0
confidence O 0
interval O 0
= O 0
2 O 0
. O 0
8 O 0
- O 0
17 O 0
. O 0
9 O 0
) O 0
. O 0

The O 0
use O 0
of O 0
cocaine B-Chemical 0
and O 0
/ O 0
or O 0
amphetamine B-Chemical 0
is O 0
a O 0
strong O 0
risk O 0
factor O 0
for O 0
stroke B-Disease 0
in O 0
this O 0
socioeconomically O 0
heterogeneous O 0
, O 0
insured O 0
urban O 0
population O 0
. O 0

Acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
subsequent O 0
to O 0
the O 0
administration O 0
of O 0
rifampicin B-Chemical 0
. O 0

A O 0
follow O 0
- O 0
up O 0
study O 0
of O 0
cases O 0
reported O 0
earlier O 0
. O 0

A O 0
clinical O 0
presentation O 0
is O 0
made O 0
of O 0
a O 0
2 O 0
- O 0
3 O 0
year O 0
follow O 0
- O 0
up O 0
of O 0
six O 0
cases O 0
of O 0
acute B-Disease 0
renal I-Disease 0
failure I-Disease 0
that O 0
have O 0
been O 0
reported O 0
earlier O 0
. O 0

The O 0
patients O 0
had O 0
developed O 0
transient O 0
renal B-Disease 0
failure I-Disease 0
after O 0
the O 0
intermittent O 0
administration O 0
of O 0
rifampicin B-Chemical 0
. O 0

The O 0
stage O 0
of O 0
olig O 0
- O 0
anuria B-Disease 0
lasted O 0
for O 0
1 O 0
- O 0
3 O 0
weeks O 0
, O 0
and O 0
five O 0
of O 0
the O 0
patients O 0
were O 0
treated O 0
by O 0
hemodialysis O 0
. O 0

Two O 0
of O 0
the O 0
patients O 0
died O 0
due O 0
to O 0
unrelated O 0
causes O 0
during O 0
the O 0
follow O 0
- O 0
up O 0
period O 0
. O 0

The O 0
four O 0
patients O 0
re O 0
- O 0
examined O 0
were O 0
clinically O 0
cured O 0
. O 0

Pathologic O 0
findings O 0
by O 0
light O 0
microscopy O 0
and O 0
immunofluorescence O 0
at O 0
biopsy O 0
were O 0
scarce O 0
. O 0

Nothing O 0
abnormal O 0
was O 0
seen O 0
by O 0
electron O 0
microscopy O 0
in O 0
two O 0
of O 0
the O 0
cases O 0
studied O 0
. O 0

Renal O 0
function O 0
was O 0
normal O 0
. O 0

In O 0
three O 0
cases O 0
the O 0
excretion O 0
at O 0
131I O 0
- O 0
hippuran O 0
renography O 0
was O 0
slightly O 0
slowed O 0
. O 0

Although O 0
in O 0
the O 0
acute O 0
stage O 0
the O 0
renal B-Disease 0
lesions I-Disease 0
histologically O 0
appeared O 0
toxic O 0
, O 0
evidence O 0
suggestive O 0
of O 0
an O 0
immunological O 0
mechanism O 0
cannot O 0
be O 0
excluded O 0
. O 0

Chronic O 0
effects O 0
of O 0
a O 0
novel O 0
synthetic O 0
anthracycline B-Chemical 0
derivative O 0
( O 0
SM B-Chemical 0
- I-Chemical 0
5887 I-Chemical 0
) O 0
on O 0
normal O 0
heart O 0
and O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
in O 0
beagle O 0
dogs O 0
. O 0

This O 0
study O 0
was O 0
designed O 0
to O 0
investigate O 0
the O 0
chronic O 0
cardiotoxic B-Disease 0
potential O 0
of O 0
SM B-Chemical 0
- I-Chemical 0
5887 I-Chemical 0
and O 0
a O 0
possible O 0
deteriorating O 0
effect O 0
of O 0
SM B-Chemical 0
- I-Chemical 0
5887 I-Chemical 0
on O 0
low O 0
- O 0
grade O 0
cardiotoxicity B-Disease 0
pre O 0
- O 0
induced O 0
by O 0
doxorubicin B-Chemical 0
in O 0
beagle O 0
dogs O 0
. O 0

In O 0
the O 0
chronic O 0
treatment O 0
, O 0
beagle O 0
dogs O 0
of O 0
each O 0
sex O 0
were O 0
given O 0
intravenously O 0
once O 0
every O 0
3 O 0
weeks O 0
, O 0
either O 0
a O 0
sublethal O 0
dose O 0
of O 0
doxorubicin B-Chemical 0
( O 0
1 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
or O 0
SM B-Chemical 0
- I-Chemical 0
5887 I-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
. O 0

The O 0
experiment O 0
was O 0
terminated O 0
3 O 0
weeks O 0
after O 0
the O 0
ninth O 0
dosing O 0
. O 0

Animals O 0
which O 0
received O 0
over O 0
six O 0
courses O 0
of O 0
doxorubicin B-Chemical 0
demonstrated O 0
the O 0
electrocardiogram O 0
( O 0
ECG O 0
) O 0
changes O 0
, O 0
decrease O 0
of O 0
blood O 0
pressure O 0
and O 0
high O 0
- O 0
grade O 0
histopathological O 0
cardiomyopathy B-Disease 0
, O 0
while O 0
animals O 0
which O 0
were O 0
terminally O 0
sacrificed O 0
after O 0
the O 0
SM B-Chemical 0
- I-Chemical 0
5887 I-Chemical 0
administration O 0
did O 0
not O 0
show O 0
any O 0
changes O 0
in O 0
ECG O 0
, O 0
blood O 0
pressure O 0
and O 0
histopathological O 0
examinations O 0
. O 0

To O 0
examine O 0
a O 0
possibly O 0
deteriorating O 0
cardiotoxic B-Disease 0
effect O 0
of O 0
SM B-Chemical 0
- I-Chemical 0
5887 I-Chemical 0
, O 0
low O 0
- O 0
grade O 0
cardiomyopathy B-Disease 0
was O 0
induced O 0
in O 0
dogs O 0
by O 0
four O 0
courses O 0
of O 0
doxorubicin B-Chemical 0
( O 0
1 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
. O 0

Nine O 0
weeks O 0
after O 0
pre O 0
- O 0
treatment O 0
, O 0
dogs O 0
were O 0
given O 0
four O 0
courses O 0
of O 0
either O 0
doxorubicin B-Chemical 0
( O 0
1 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
or O 0
SM B-Chemical 0
- I-Chemical 0
5887 I-Chemical 0
( O 0
2 O 0
. O 0
5 O 0
mg O 0
/ O 0
kg O 0
) O 0
once O 0
every O 0
3 O 0
weeks O 0
. O 0

The O 0
low O 0
- O 0
grade O 0
cardiotoxic B-Disease 0
changes O 0
were O 0
enhanced O 0
by O 0
the O 0
additional O 0
doxorubicin B-Chemical 0
treatment O 0
. O 0

On O 0
the O 0
contrary O 0
, O 0
the O 0
SM B-Chemical 0
- I-Chemical 0
5887 I-Chemical 0
treatment O 0
did O 0
not O 0
progress O 0
the O 0
grade O 0
of O 0
cardiomyopathy B-Disease 0
. O 0

In O 0
conclusion O 0
, O 0
SM B-Chemical 0
- I-Chemical 0
5887 I-Chemical 0
does O 0
not O 0
have O 0
any O 0
potential O 0
of O 0
chronic O 0
cardiotoxicity B-Disease 0
and O 0
deteriorating O 0
effect O 0
on O 0
doxorubicin B-Chemical 0
- O 0
induced O 0
cardiotoxicity B-Disease 0
in O 0
dogs O 0
. O 0

Risk O 0
for O 0
valvular B-Disease 0
heart I-Disease 0
disease I-Disease 0
among O 0
users O 0
of O 0
fenfluramine B-Chemical 0
and O 0
dexfenfluramine B-Chemical 0
who O 0
underwent O 0
echocardiography O 0
before O 0
use O 0
of O 0
medication O 0
. O 0

BACKGROUND O 0
: O 0
Because O 0
uncontrolled O 0
echocardiographic O 0
surveys O 0
suggested O 0
that O 0
up O 0
to O 0
30 O 0
% O 0
to O 0
38 O 0
% O 0
of O 0
users O 0
of O 0
fenfluramine B-Chemical 0
and O 0
dexfenfluramine B-Chemical 0
had O 0
valvular B-Disease 0
disease I-Disease 0
, O 0
these O 0
drugs O 0
were O 0
withdrawn O 0
from O 0
the O 0
market O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
determine O 0
the O 0
risk O 0
for O 0
new O 0
or O 0
worsening O 0
valvular B-Disease 0
abnormalities I-Disease 0
among O 0
users O 0
of O 0
fenfluramine B-Chemical 0
or O 0
dexfenfluramine B-Chemical 0
who O 0
underwent O 0
echocardiography O 0
before O 0
they O 0
began O 0
to O 0
take O 0
these O 0
medications O 0
. O 0

DESIGN O 0
: O 0
Cohort O 0
study O 0
. O 0

SETTING O 0
: O 0
Academic O 0
primary O 0
care O 0
practices O 0
. O 0

PATIENTS O 0
: O 0
46 O 0
patients O 0
who O 0
used O 0
fenfluramine B-Chemical 0
or O 0
dexfenfluramine B-Chemical 0
for O 0
14 O 0
days O 0
or O 0
more O 0
and O 0
had O 0
echocardiograms O 0
obtained O 0
before O 0
therapy O 0
. O 0

MEASUREMENTS O 0
: O 0
Follow O 0
- O 0
up O 0
echocardiography O 0
. O 0

The O 0
primary O 0
outcome O 0
was O 0
new O 0
or O 0
worsening O 0
valvulopathy B-Disease 0
, O 0
defined O 0
as O 0
progression O 0
of O 0
either O 0
aortic B-Disease 0
or I-Disease 0
mitral I-Disease 0
regurgitation I-Disease 0
by O 0
at O 0
least O 0
one O 0
degree O 0
of O 0
severity O 0
and O 0
disease O 0
that O 0
met O 0
U O 0
. O 0
S O 0
. O 0

Food O 0
and O 0
Drug O 0
Administration O 0
criteria O 0
( O 0
at O 0
least O 0
mild O 0
aortic B-Disease 0
regurgitation I-Disease 0
or O 0
moderate O 0
mitral B-Disease 0
regurgitation I-Disease 0
) O 0
. O 0

RESULTS O 0
: O 0
Two O 0
patients O 0
( O 0
4 O 0
. O 0
3 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
to O 0
14 O 0
. O 0
8 O 0
% O 0
] O 0
) O 0
receiving O 0
fenfluramine B-Chemical 0
- O 0
phentermine B-Chemical 0
developed O 0
valvular B-Disease 0
heart I-Disease 0
disease I-Disease 0
. O 0

One O 0
had O 0
baseline O 0
bicuspid B-Disease 0
aortic I-Disease 0
valve I-Disease 0
and O 0
mild O 0
aortic B-Disease 0
regurgitation I-Disease 0
that O 0
progressed O 0
to O 0
moderate O 0
regurgitation O 0
. O 0

The O 0
second O 0
patient O 0
developed O 0
new O 0
moderate O 0
aortic B-Disease 0
insufficiency I-Disease 0
. O 0

CONCLUSION O 0
: O 0
Users O 0
of O 0
diet O 0
medications O 0
are O 0
at O 0
risk O 0
for O 0
valvular B-Disease 0
heart I-Disease 0
disease I-Disease 0
. O 0

However O 0
, O 0
the O 0
incidence O 0
may O 0
be O 0
lower O 0
than O 0
that O 0
reported O 0
previously O 0
. O 0

Therapeutic O 0
drug O 0
monitoring O 0
of O 0
tobramycin B-Chemical 0
: O 0
once O 0
- O 0
daily O 0
versus O 0
twice O 0
- O 0
daily O 0
dosage O 0
schedules O 0
. O 0

OBJECTIVE O 0
: O 0
To O 0
evaluate O 0
the O 0
effect O 0
of O 0
dosage O 0
regimen O 0
( O 0
once O 0
- O 0
daily O 0
vs O 0
. O 0
twice O 0
- O 0
daily O 0
) O 0
of O 0
tobramicyn B-Chemical 0
on O 0
steady O 0
- O 0
state O 0
serum O 0
concentrations O 0
and O 0
toxicity B-Disease 0
. O 0

MATERIALS O 0
AND O 0
METHODS O 0
: O 0
Patients O 0
undergoing O 0
treatment O 0
with O 0
i O 0
. O 0
v O 0
. O 0
tobramycin B-Chemical 0
( O 0
4 O 0
mg O 0
/ O 0
kg O 0
/ O 0
day O 0
) O 0
were O 0
randomised O 0
to O 0
two O 0
groups O 0
. O 0

Group O 0
OD O 0
( O 0
n O 0
= O 0
22 O 0
) O 0
received O 0
a O 0
once O 0
- O 0
daily O 0
dose O 0
of O 0
tobramycin B-Chemical 0
and O 0
group O 0
TD O 0
( O 0
n O 0
= O 0
21 O 0
) O 0
received O 0
the O 0
same O 0
dose O 0
divided O 0
into O 0
two O 0
doses O 0
daily O 0
. O 0

Tobramycin B-Chemical 0
serum O 0
concentrations O 0
( O 0
peak O 0
and O 0
trough O 0
) O 0
were O 0
measured O 0
by O 0
enzyme O 0
multiplied O 0
immunoassay O 0
. O 0

The O 0
renal O 0
and O 0
auditory O 0
functions O 0
of O 0
the O 0
patients O 0
were O 0
monitored O 0
before O 0
, O 0
during O 0
and O 0
immediately O 0
after O 0
treatment O 0
. O 0

RESULTS O 0
: O 0
The O 0
two O 0
groups O 0
were O 0
comparable O 0
with O 0
respect O 0
to O 0
sex O 0
, O 0
age O 0
, O 0
body O 0
weight O 0
and O 0
renal O 0
function O 0
. O 0

No O 0
statistically O 0
significant O 0
differences O 0
were O 0
found O 0
in O 0
mean O 0
daily O 0
dose O 0
, O 0
duration O 0
of O 0
treatment O 0
, O 0
or O 0
cumulative O 0
dose O 0
. O 0

Trough O 0
concentrations O 0
were O 0
< O 0
2 O 0
g O 0
/ O 0
ml O 0
in O 0
the O 0
two O 0
groups O 0
( O 0
100 O 0
% O 0
) O 0
. O 0

Peak O 0
concentrations O 0
were O 0
> O 0
6 O 0
microg O 0
/ O 0
ml O 0
in O 0
100 O 0
% O 0
of O 0
the O 0
OD O 0
group O 0
and O 0
in O 0
67 O 0
% O 0
of O 0
the O 0
TD O 0
group O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

Mean O 0
peak O 0
concentrations O 0
were O 0
markedly O 0
different O 0
: O 0
11 O 0
. O 0
00 O 0
+ O 0
/ O 0
- O 0
2 O 0
. O 0
89 O 0
microg O 0
/ O 0
ml O 0
in O 0
OD O 0
vs O 0
. O 0
6 O 0
. O 0
53 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
45 O 0
microg O 0
/ O 0
ml O 0
in O 0
TD O 0
( O 0
P O 0
< O 0
0 O 0
. O 0
01 O 0
) O 0
. O 0

The O 0
pharmacokinetics O 0
parameters O 0
were O 0
: O 0
Ke O 0
, O 0
( O 0
0 O 0
. O 0
15 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
03 O 0
/ O 0
h O 0
in O 0
OD 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
06 O 0
/ O 0
h O 0
in O 0
TD O 0
) O 0
, O 0
t1 O 0
/ O 0
2 O 0
, O 0
( O 0
4 O 0
. O 0
95 O 0
+ O 0
/ O 0
- O 0
1 O 0
. O 0
41 O 0
h O 0
in O 0
OD O 0
vs O 0
. O 0
3 O 0
. O 0
07 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
71 O 0
h O 0
in O 0
TD O 0
) O 0
, O 0
Vd O 0
( O 0
0 O 0
. O 0
35 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
11 O 0
l O 0
/ O 0
kg O 0
in O 0
OD O 0
vs O 0
. O 0
0 O 0
. O 0
33 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
09 O 0
l O 0
/ O 0
kg O 0
in O 0
TD O 0
) O 0
, O 0
Cl O 0
( O 0
0 O 0
. O 0
86 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
29 O 0
ml O 0
/ O 0
min O 0
/ O 0
kg O 0
in O 0
OD O 0
vs O 0
. O 0
1 O 0
. O 0
28 O 0
+ O 0
/ O 0
- O 0
0 O 0
. O 0
33 O 0
ml O 0
/ O 0
min O 0
/ O 0
kg O 0
in O 0
TD O 0
) O 0
. O 0

Increased O 0
serum O 0
creatinine B-Chemical 0
was O 0
observed O 0
in O 0
73 O 0
% O 0
of O 0
patients O 0
in O 0
OD O 0
versus O 0
57 O 0
% O 0
of O 0
patients O 0
in O 0
TD O 0
, O 0
without O 0
evidence O 0
of O 0
nephrotoxicity B-Disease 0
. O 0

In O 0
TD O 0
group O 0
, O 0
three O 0
patients O 0
developed O 0
decreased B-Disease 0
auditory I-Disease 0
function I-Disease 0
, O 0
of O 0
which O 0
one O 0
presented O 0
with O 0
an O 0
auditory B-Disease 0
loss I-Disease 0
of O 0
- O 0
30 O 0
dB O 0
, O 0
whereas O 0
in O 0
the O 0
OD O 0
group O 0
only O 0
one O 0
patient O 0
presented O 0
decreased B-Disease 0
auditory I-Disease 0
function I-Disease 0
. O 0

CONCLUSION O 0
: O 0
This O 0
small O 0
study O 0
suggests O 0
that O 0
a O 0
once O 0
- O 0
daily O 0
dosing O 0
regimen O 0
of O 0
tobramycin B-Chemical 0
is O 0
at O 0
least O 0
as O 0
effective O 0
as O 0
and O 0
is O 0
no O 0
more O 0
and O 0
possibly O 0
less O 0
toxic O 0
than O 0
the O 0
twice O 0
- O 0
daily O 0
regimen O 0
. O 0

Using O 0
a O 0
single O 0
- O 0
dose O 0
therapy O 0
, O 0
peak O 0
concentration O 0
determination O 0
is O 0
not O 0
necessary O 0
, O 0
only O 0
trough O 0
samples O 0
should O 0
be O 0
monitored O 0
to O 0
ensure O 0
levels O 0
below O 0
2 O 0
microg O 0
/ O 0
ml O 0
. O 0

Enhanced O 0
bradycardia B-Disease 0
induced O 0
by O 0
beta O 0
- O 0
adrenoceptor O 0
antagonists O 0
in O 0
rats O 0
pretreated O 0
with O 0
isoniazid B-Chemical 0
. O 0

High O 0
doses O 0
of O 0
isoniazid B-Chemical 0
increase O 0
hypotension B-Disease 0
induced O 0
by O 0
vasodilators O 0
and O 0
change O 0
the O 0
accompanying O 0
reflex O 0
tachycardia B-Disease 0
to O 0
bradycardia B-Disease 0
, O 0
an O 0
interaction O 0
attributed O 0
to O 0
decreased O 0
synthesis O 0
of O 0
brain 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

In O 0
the O 0
present O 0
study O 0
, O 0
the O 0
possible O 0
enhancement O 0
by O 0
isoniazid B-Chemical 0
of O 0
bradycardia B-Disease 0
induced O 0
by O 0
beta O 0
- O 0
adrenoceptor O 0
antagonists O 0
was O 0
determined O 0
in O 0
rats O 0
anaesthetised O 0
with O 0
chloralose B-Chemical 0
- O 0
urethane B-Chemical 0
. O 0

Isoniazid B-Chemical 0
significantly O 0
increased O 0
bradycardia B-Disease 0
after O 0
propranolol B-Chemical 0
, O 0
pindolol B-Chemical 0
, O 0
labetalol B-Chemical 0
and O 0
atenolol B-Chemical 0
, O 0
as O 0
well O 0
as O 0
after O 0
clonidine B-Chemical 0
, O 0
but O 0
not O 0
after O 0
hexamethonium B-Chemical 0
or O 0
carbachol B-Chemical 0
. O 0

Enhancement O 0
was O 0
not O 0
observed O 0
in O 0
rats O 0
pretreated O 0
with O 0
methylatropine B-Chemical 0
or O 0
previously O 0
vagotomised O 0
. O 0

These O 0
results O 0
are O 0
compatible O 0
with O 0
interference O 0
by O 0
isoniazid B-Chemical 0
with O 0
GABAergic O 0
inhibition O 0
of O 0
cardiac O 0
parasympathetic O 0
tone O 0
. O 0

Such O 0
interference O 0
could O 0
be O 0
exerted O 0
centrally O 0
, O 0
possibly O 0
at O 0
the O 0
nucleus O 0
ambiguus O 0
, O 0
or O 0
peripherally O 0
at O 0
the O 0
sinus O 0
node O 0
. O 0

Structural B-Disease 0
and I-Disease 0
functional I-Disease 0
impairment I-Disease 0
of I-Disease 0
mitochondria I-Disease 0
in O 0
adriamycin B-Chemical 0
- O 0
induced O 0
cardiomyopathy B-Disease 0
in O 0
mice O 0
: O 0
suppression O 0
of O 0
cytochrome O 0
c O 0
oxidase O 0
II O 0
gene O 0
expression O 0
. O 0

The O 0
use O 0
of O 0
adriamycin B-Chemical 0
( O 0
ADR B-Chemical 0
) O 0
in O 0
cancer B-Disease 0
chemotherapy O 0
has O 0
been O 0
limited O 0
due O 0
to O 0
its O 0
cumulative O 0
cardiovascular B-Disease 0
toxicity I-Disease 0
. O 0

Earlier O 0
observations O 0
that O 0
ADR B-Chemical 0
interacts O 0
with O 0
mitochondrial O 0
cytochrome O 0
c O 0
oxidase O 0
( O 0
COX O 0
) O 0
and O 0
suppresses O 0
its O 0
enzyme O 0
activity O 0
led O 0
us O 0
to O 0
investigate O 0
ADR B-Chemical 0
' O 0
s O 0
action O 0
on O 0
the O 0
cardiovascular O 0
functions O 0
and O 0
heart O 0
mitochondrial O 0
morphology O 0
in O 0
Balb O 0
- O 0
c O 0
mice O 0
i O 0
. O 0
p O 0
. O 0
treated O 0
with O 0
ADR B-Chemical 0
for O 0
several O 0
weeks O 0
. O 0

At O 0
various O 0
times O 0
during O 0
treatment O 0
, O 0
the O 0
animals O 0
were O 0
assessed O 0
for O 0
cardiovascular O 0
functions O 0
by O 0
electrocardiography O 0
and O 0
for O 0
heart O 0
tissue O 0
damage O 0
by O 0
electron O 0
microscopy O 0
. O 0

In O 0
parallel O 0
, O 0
total O 0
RNA O 0
was O 0
extracted O 0
from O 0
samples O 0
of O 0
dissected O 0
heart O 0
and O 0
analyzed O 0
by O 0
Northern O 0
blot O 0
hybridization O 0
to O 0
determine O 0
the O 0
steady O 0
- O 0
state O 0
level O 0
of O 0
three O 0
RNA O 0
transcripts O 0
encoded O 0
by O 0
the O 0
COXII O 0
, O 0
COXIII O 0
, O 0
and O 0
COXIV O 0
genes O 0
. O 0

Similarly O 0
, O 0
samples O 0
obtained O 0
from O 0
the O 0
liver O 0
of O 0
the O 0
same O 0
animals O 0
were O 0
analyzed O 0
for O 0
comparative O 0
studies O 0
. O 0

Our O 0
results O 0
indicated O 0
that O 0
1 O 0
) O 0
treatment O 0
of O 0
mice O 0
with O 0
ADR B-Chemical 0
caused O 0
cardiovascular B-Disease 0
arrhythmias I-Disease 0
characterized O 0
by O 0
bradycardia B-Disease 0
, O 0
extension O 0
of O 0
ventricular O 0
depolarization O 0
time O 0
( O 0
tQRS O 0
) O 0
, O 0
and O 0
failure O 0
of O 0
QRS O 0
at O 0
high O 0
concentrations O 0
( O 0
10 O 0
- O 0
14 O 0
mg O 0
/ O 0
kg O 0
body O 0
weight O 0
cumulative O 0
dose O 0
) O 0
; O 0
2 O 0
) O 0
the O 0
heart O 0
mitochondria O 0
underwent O 0
swelling B-Disease 0
, O 0
fusion O 0
, O 0
dissolution O 0
, O 0
and O 0
/ O 0
or O 0
disruption O 0
of O 0
mitochondrial O 0
cristae O 0
after O 0
several O 0
weeks O 0
of O 0
treatment O 0
. O 0

Such O 0
abnormalities O 0
were O 0
not O 0
observed O 0
in O 0
the O 0
mitochondria O 0
of O 0
liver O 0
tissue O 0
; O 0
and O 0
3 O 0
) O 0
among O 0
the O 0
three O 0
genes O 0
of O 0
COX O 0
enzyme O 0
examined O 0
, O 0
only O 0
COXII O 0
gene O 0
expression O 0
was O 0
suppressed O 0
by O 0
ADR B-Chemical 0
treatment O 0
, O 0
mainly O 0
after O 0
8 O 0
weeks O 0
in O 0
both O 0
heart O 0
and O 0
liver O 0
. O 0

Knowing O 0
that O 0
heart O 0
mitochondria O 0
represent O 0
almost O 0
40 O 0
% O 0
of O 0
heart O 0
muscle O 0
by O 0
weight O 0
, O 0
we O 0
conclude O 0
that O 0
the O 0
deteriorating O 0
effects O 0
of O 0
ADR B-Chemical 0
on O 0
cardiovascular O 0
function O 0
involve O 0
mitochondrial B-Disease 0
structural I-Disease 0
and I-Disease 0
functional I-Disease 0
impairment I-Disease 0
. O 0

