22	1
-	2
oxacalcitriol	2
suppresses	0
secondary	3
hyperparathyroidism	4
without	0
inducing	0
low	3
bone	4
turnover	4
in	0
dogs	0
with	0
renal	3
failure	4
.	0

BACKGR0UND	0
:	0
Calcitriol	1
therapy	0
suppresses	0
serum	0
levels	0
of	0
parathyroid	0
hormone	0
(	0
PTH	0
)	0
in	0
patients	0
with	0
renal	3
failure	4
but	0
has	0
several	0
drawbacks	0
,	0
including	0
hypercalcemia	3
and	0
/	0
or	0
marked	0
suppression	3
of	4
bone	4
turnover	4
,	0
which	0
may	0
lead	0
to	0
adynamic	3
bone	4
disease	4
.	0

A	0
new	0
vitamin	1
D	2
analogue	0
,	0
22	1
-	2
oxacalcitriol	2
(	0
0CT	1
)	0
,	0
has	0
been	0
shown	0
to	0
have	0
promising	0
characteristics	0
.	0

This	0
study	0
was	0
undertaken	0
to	0
determine	0
the	0
effects	0
of	0
0CT	1
on	0
serum	0
PTH	0
levels	0
and	0
bone	0
turnover	0
in	0
states	0
of	0
normal	0
or	0
impaired	3
renal	4
function	4
.	0

METH0DS	0
:	0
Sixty	0
dogs	0
were	0
either	0
nephrectomized	0
(	0
Nx	0
,	0
N	0
=	0
38	0
)	0
or	0
sham	0
-	0
operated	0
(	0
Sham	0
,	0
N	0
=	0
22	0
)	0
.	0

The	0
animals	0
received	0
supplemental	0
phosphate	1
to	0
enhance	0
PTH	0
secretion	0
.	0

Fourteen	0
weeks	0
after	0
the	0
start	0
of	0
phosphate	1
supplementation	0
,	0
half	0
of	0
the	0
Nx	0
and	0
Sham	0
dogs	0
received	0
doses	0
of	0
0CT	1
(	0
three	0
times	0
per	0
week	0
)	0
;	0
the	0
other	0
half	0
were	0
given	0
vehicle	0
for	0
60	0
weeks	0
.	0

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

Biochemical	0
and	0
hormonal	0
indices	0
of	0
calcium	1
and	0
bone	0
metabolism	0
were	0
measured	0
throughout	0
the	0
study	0
,	0
and	0
bone	0
biopsies	0
were	0
done	0
at	0
baseline	0
,	0
60	0
weeks	0
after	0
0CT	1
or	0
vehicle	0
treatment	0
,	0
and	0
at	0
the	0
end	0
of	0
the	0
crossover	0
period	0
.	0

RESULTS	0
:	0
In	0
Nx	0
dogs	0
,	0
0CT	1
significantly	0
decreased	0
serum	0
PTH	0
levels	0
soon	0
after	0
the	0
induction	0
of	0
renal	3
insufficiency	4
.	0

In	0
long	0
-	0
standing	0
secondary	3
hyperparathyroidism	4
,	0
0CT	1
(	0
0	0
.	0
03	0
microg	0
/	0
kg	0
)	0
stabilized	0
serum	0
PTH	0
levels	0
during	0
the	0
first	0
months	0
.	0

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

These	0
effects	0
were	0
accompanied	0
by	0
episodes	0
of	0
hypercalcemia	3
and	0
hyperphosphatemia	3
.	0

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

In	0
Nx	0
dogs	0
,	0
0CT	1
reversed	0
abnormal	0
bone	0
formation	0
,	0
such	0
as	0
woven	3
osteoid	4
and	0
fibrosis	3
,	0
but	0
did	0
not	0
significantly	0
alter	0
the	0
level	0
of	0
bone	0
turnover	0
.	0

In	0
addition	0
,	0
0CT	1
improved	0
mineralization	0
lag	0
time	0
,	0
(	0
that	0
is	0
,	0
the	0
rate	0
at	0
which	0
osteoid	0
mineralizes	0
)	0
in	0
both	0
Nx	0
and	0
Sham	0
dogs	0
.	0

C0NCLUSI0NS	0
:	0
These	0
results	0
indicate	0
that	0
even	0
though	0
0CT	1
does	0
not	0
completely	0
prevent	0
the	0
occurrence	0
of	0
hypercalcemia	3
in	0
experimental	0
dogs	0
with	0
renal	3
insufficiency	4
,	0
it	0
may	0
be	0
of	0
use	0
in	0
the	0
management	0
of	0
secondary	3
hyperparathyroidism	4
because	0
it	0
does	0
not	0
induce	0
low	3
bone	4
turnover	4
and	0
,	0
therefore	0
,	0
does	0
not	0
increase	0
the	0
risk	0
of	0
adynamic	3
bone	4
disease	4
.	0

Hypotension	3
,	0
bradycardia	3
,	0
and	0
asystole	3
after	0
high	0
-	0
dose	0
intravenous	0
methylprednisolone	1
in	0
a	0
monitored	0
patient	0
.	0

We	0
report	0
a	0
case	0
of	0
hypotension	3
,	0
bradycardia	3
,	0
and	0
asystole	3
after	0
intravenous	0
administration	0
of	0
high	0
-	0
dose	0
methylprednisolone	1
in	0
a	0
73	0
-	0
year	0
-	0
old	0
patient	0
who	0
underwent	0
electrocardiographic	0
(	0
ECG	0
)	0
monitoring	0
throughout	0
the	0
episode	0
.	0

There	0
was	0
a	0
history	0
of	0
ischemic	3
cardiac	3
disease	4
9	0
years	0
earlier	0
.	0

The	0
patient	0
was	0
admitted	0
with	0
a	0
pulmonary	3
-	4
renal	4
syndrome	4
with	0
hemoptysis	3
,	0
rapidly	0
progressive	0
renal	3
failure	4
,	0
and	0
hypoxemia	3
that	0
required	0
mechanical	0
ventilation	0
in	0
the	0
intensive	0
care	0
unit	0
.	0

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

The	0
ECG	0
showed	0
a	0
junctional	0
rhythm	0
without	0
ventricular	3
arrhythmia	4
.	0

This	0
study	0
reviews	0
the	0
current	0
proposed	0
mechanisms	0
of	0
sudden	3
death	4
after	0
a	0
high	0
dose	0
of	0
intravenous	0
methylprednisolone	1
(	0
IVMP	1
)	0
.	0

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

Rapid	0
infusion	0
and	0
underlying	0
cardiac	3
disease	4
were	0
important	0
risk	0
factors	0
in	0
the	0
case	0
reported	0
here	0
,	0
and	0
the	0
authors	0
discount	0
ventricular	3
arrhythmia	4
as	0
the	0
main	0
mechanism	0
.	0

Worsening	0
of	0
levodopa	1
-	0
induced	0
dyskinesias	3
by	0
motor	0
and	0
mental	0
tasks	0
.	0

Ten	0
patients	0
who	0
had	0
Parkinson	3
'	4
s	4
disease	4
with	0
disabling	0
dyskinesia	3
were	0
included	0
in	0
this	0
study	0
to	0
evaluate	0
the	0
role	0
of	0
mental	0
(	0
mental	0
calculation	0
)	0
and	0
motor	0
(	0
flexion	0
/	0
extension	0
of	0
right	0
fingers	0
,	0
flexion	0
/	0
extension	0
of	0
left	0
fingers	0
,	0
flexion	0
/	0
extension	0
of	0
the	0
neck	0
,	0
speaking	0
aloud	0
)	0
tasks	0
on	0
the	0
worsening	0
of	0
peak	0
-	0
dose	0
dyskinesia	3
following	0
administration	0
of	0
an	0
effective	0
single	0
dose	0
of	0
apomorphine	1
.	0

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

These	0
results	0
suggest	0
that	0
activation	0
tasks	0
such	0
as	0
"	0
speaking	0
aloud	0
"	0
could	0
be	0
used	0
for	0
objective	0
assessment	0
of	0
dyskinesia	3
severity	0
.	0

Urine	0
N	0
-	0
acetyl	0
-	0
beta	0
-	0
D	0
-	0
glucosaminidase	0
-	0
-	0
a	0
marker	0
of	0
tubular	0
damage	0
?	0

BACKGR0UND	0
:	0
Although	0
an	0
indicator	0
of	0
renal	3
tubular	4
dysfunction	4
,	0
an	0
increased	0
urinary	0
N	0
-	0
acetyl	0
-	0
beta	0
-	0
D	0
-	0
glucosaminidase	0
(	0
NAG	0
)	0
activity	0
might	0
reflect	0
increased	0
lysosomal	0
activity	0
in	0
renal	0
tubular	0
cells	0
.	0

METH0DS	0
:	0
Puromycin	1
aminonucleoside	2
(	0
PAN	1
)	0
was	0
administered	0
to	0
Sprague	0
Dawley	0
rats	0
to	0
induce	0
proteinuria	3
.	0

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

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

RESULTS	0
:	0
Following	0
intravenous	0
PAN	1
urine	0
volume	0
and	0
urine	0
NAG	0
activity	0
increased	0
significantly	0
by	0
day	0
two	0
,	0
but	0
returned	0
to	0
normal	0
by	0
day	0
four	0
.	0

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

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

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

Peak	0
urine	0
NAG	0
activity	0
and	0
a	0
change	0
in	0
NAG	0
isoenzyme	0
pattern	0
coincided	0
with	0
both	0
the	0
peak	0
proteinuria	3
and	0
the	0
reduction	0
in	0
intracellular	0
protein	0
and	0
NAG	0
droplets	0
(	0
day	0
six	0
onwards	0
)	0
.	0

C0NCLUSI0NS	0
:	0
This	0
animal	0
model	0
demonstrates	0
that	0
an	0
increase	0
in	0
lysosomal	0
turnover	0
and	0
hence	0
urine	0
NAG	0
activity	0
,	0
occurs	0
when	0
increased	0
protein	0
is	0
presented	0
to	0
the	0
tubular	0
cells	0
.	0

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

Cauda	3
equina	4
syndrome	4
after	0
spinal	0
anaesthesia	0
with	0
hyperbaric	0
5	0
%	0
lignocaine	1
:	0
a	0
review	0
of	0
six	0
cases	0
of	0
cauda	3
equina	4
syndrome	4
reported	0
to	0
the	0
Swedish	0
Pharmaceutical	0
Insurance	0
1993	0
-	0
1997	0
.	0

Six	0
cases	0
of	0
cauda	3
equina	4
syndrome	4
with	0
varying	0
severity	0
were	0
reported	0
to	0
the	0
Swedish	0
Pharmaceutical	0
Insurance	0
during	0
the	0
period	0
1993	0
-	0
1997	0
.	0

All	0
were	0
associated	0
with	0
spinal	0
anaesthesia	0
using	0
hyperbaric	0
5	0
%	0
lignocaine	1
.	0

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

The	0
dose	0
of	0
hyperbaric	0
5	0
%	0
lignocaine	1
administered	0
ranged	0
from	0
60	0
to	0
120	0
mg	0
.	0

Three	0
of	0
the	0
cases	0
were	0
most	0
likely	0
caused	0
by	0
direct	0
neurotoxicity	3
of	0
hyperbaric	0
5	0
%	0
lignocaine	1
.	0

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

All	0
cases	0
sustained	0
permanent	0
neurological	3
deficits	4
.	0

We	0
recommend	0
that	0
hyperbaric	0
lignocaine	1
should	0
be	0
administered	0
in	0
concentrations	0
not	0
greater	0
than	0
2	0
%	0
and	0
at	0
a	0
total	0
dose	0
preferably	0
not	0
exceeding	0
60	0
mg	0
.	0

Systemic	0
toxicity	3
following	0
administration	0
of	0
sirolimus	1
(	0
formerly	0
rapamycin	1
)	0
for	0
psoriasis	3
:	0
association	0
of	0
capillary	3
leak	4
syndrome	4
with	0
apoptosis	0
of	0
lesional	0
lymphocytes	0
.	0

BACKGR0UND	0
:	0
Sirolimus	1
(	0
formerly	0
rapamycin	1
)	0
is	0
an	0
immunosuppressive	0
agent	0
that	0
interferes	0
with	0
T	0
-	0
cell	0
activation	0
.	0

After	0
2	0
individuals	0
with	0
psoriasis	3
developed	0
a	0
capillary	3
leak	4
syndrome	4
following	0
treatment	0
with	0
oral	0
sirolimus	1
lesional	0
skin	0
cells	0
and	0
activated	0
peripheral	0
blood	0
cells	0
were	0
analyzed	0
for	0
induction	0
of	0
apoptosis	0
.	0

0BSERVATI0NS	0
:	0
A	0
keratome	0
skin	0
specimen	0
from	0
1	0
patient	0
with	0
sirolimus	1
-	0
induced	0
capillary	3
leak	4
syndrome	4
had	0
a	0
2	0
.	0
3	0
-	0
fold	0
increase	0
in	0
percentage	0
of	0
apoptotic	0
cells	0
(	0
to	0
48	0
%	0
)	0
compared	0
with	0
an	0
unaffected	0
sirolimus	1
-	0
treated	0
patient	0
with	0
psoriasis	3
(	0
21	0
%	0
)	0
.	0

Activated	0
peripheral	0
blood	0
T	0
cells	0
from	0
patients	0
with	0
psoriasis	3
tended	0
to	0
exhibit	0
greater	0
spontaneous	0
or	0
dexamethasone	1
-	0
induced	0
apoptosis	0
than	0
did	0
normal	0
T	0
cells	0
,	0
particularly	0
in	0
the	0
presence	0
of	0
sirolimus	1
.	0

C0NCLUSI0NS	0
:	0
Severe	0
adverse	0
effects	0
of	0
sirolimus	1
include	0
fever	3
,	0
anemia	3
,	0
and	0
capillary	3
leak	4
syndrome	4
.	0

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

Because	0
patients	0
with	0
severe	0
psoriasis	3
may	0
develop	0
capillary	3
leak	4
from	0
various	0
systemic	0
therapies	0
,	0
clinical	0
monitoring	0
is	0
advisable	0
for	0
patients	0
with	0
inflammatory	3
diseases	4
who	0
are	0
treated	0
with	0
immune	0
modulators	0
.	0

Effect	0
of	0
lithium	1
maintenance	0
therapy	0
on	0
thyroid	0
and	0
parathyroid	0
function	0
.	0

0BJECTIVES	0
:	0
To	0
assess	0
changes	0
induced	0
by	0
lithium	1
maintenance	0
therapy	0
on	0
the	0
incidence	0
of	0
thyroid	0
,	0
parathyroid	0
and	0
ion	0
alterations	0
.	0

These	0
were	0
evaluated	0
with	0
respect	0
to	0
the	0
duration	0
of	0
lithium	1
therapy	0
,	0
age	0
,	0
sex	0
,	0
and	0
family	0
history	0
(	0
whether	0
or	0
not	0
the	0
patient	0
had	0
a	0
first	0
-	0
degree	0
relative	0
with	0
thyroid	3
disease	4
)	0
.	0

DESIGN	0
:	0
Prospective	0
study	0
.	0

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

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

PATIENTS	0
:	0
0ne	0
hundred	0
and	0
one	0
patients	0
(	0
28	0
men	0
and	0
73	0
women	0
)	0
with	0
bipolar	3
disorder	4
receiving	0
lithium	1
maintenance	0
therapy	0
ranging	0
from	0
1	0
year	0
'	0
s	0
to	0
32	0
years	0
'	0
duration	0
.	0

The	0
control	0
group	0
consisted	0
of	0
82	0
patients	0
with	0
no	0
psychiatric	3
or	0
endocrinological	0
diagnoses	0
from	0
the	0
hospital	0
'	0
s	0
out	0
-	0
patient	0
clinics	0
.	0

0UTC0ME	0
MEASURES	0
:	0
Laboratory	0
analyses	0
of	0
calcium	1
,	0
magnesium	1
and	0
thyroid	0
-	0
stimulating	0
hormone	0
levels	0
performed	0
before	0
beginning	0
lithium	1
therapy	0
and	0
at	0
biannual	0
follow	0
-	0
up	0
.	0

RESULTS	0
:	0
Hypothyroidism	3
developed	0
in	0
40	0
patients	0
,	0
excluding	0
8	0
patients	0
who	0
were	0
hypothyroid	3
at	0
baseline	0
.	0

All	0
patients	0
having	0
first	0
-	0
degree	0
relatives	0
affected	0
by	0
thyroid	3
illness	4
had	0
accelerated	0
onset	0
of	0
hypothyroidism	3
(	0
3	0
.	0
7	0
years	0
after	0
onset	0
of	0
lithium	1
therapy	0
)	0
compared	0
with	0
patients	0
without	0
a	0
family	0
history	0
(	0
8	0
.	0
6	0
years	0
after	0
onset	0
of	0
lithium	1
therapy	0
)	0
.	0

Women	0
over	0
60	0
years	0
of	0
age	0
were	0
more	0
often	0
affected	0
by	0
hypothyroidism	3
than	0
women	0
under	0
60	0
years	0
of	0
age	0
(	0
34	0
.	0
6	0
%	0
versus	0
31	0
.	0
9	0
%	0
)	0
.	0

Magnesium	1
levels	0
in	0
patients	0
on	0
lithium	1
treatment	0
were	0
unchanged	0
from	0
baseline	0
levels	0
.	0

After	0
lithium	1
treatment	0
,	0
calcium	1
levels	0
were	0
higher	0
than	0
either	0
baseline	0
levels	0
or	0
control	0
levels	0
.	0

Thus	0
,	0
lithium	1
treatment	0
counteracted	0
the	0
decrease	0
in	0
plasma	0
calcium	1
levels	0
associated	0
with	0
aging	0
.	0

C0NCLUSI0NS	0
:	0
Familial	0
thyroid	3
illness	4
is	0
a	0
risk	0
factor	0
for	0
hypothyroidism	3
and	0
hypercalcemia	3
during	0
lithium	1
therapy	0
.	0

Severe	0
immune	0
hemolytic	3
anemia	4
associated	0
with	0
prophylactic	0
use	0
of	0
cefotetan	1
in	0
obstetric	0
and	0
gynecologic	0
procedures	0
.	0

Second	0
-	0
and	0
third	0
-	0
generation	0
cephalosporins	1
,	0
especially	0
cefotetan	1
,	0
are	0
increasingly	0
associated	0
with	0
severe	0
,	0
sometimes	0
fatal	0
immune	0
hemolytic	3
anemia	4
.	0

We	0
noticed	0
that	0
10	0
of	0
our	0
35	0
cases	0
of	0
cefotetan	1
-	0
induced	0
hemolytic	3
anemias	4
were	0
in	0
patients	0
who	0
had	0
received	0
cefotetan	1
prophylactically	0
for	0
obstetric	0
and	0
gynecologic	0
procedures	0
.	0

Eight	0
of	0
these	0
cases	0
of	0
severe	0
immune	0
hemolytic	3
anemia	4
are	0
described	0
.	0

Effects	0
of	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
drugs	0
on	0
hemostasis	0
in	0
patients	0
with	0
aneurysmal	3
subarachnoid	4
hemorrhage	4
.	0

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

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

Patients	0
with	0
aneurysmal	3
subarachnoid	4
hemorrhage	4
(	0
SAH	3
)	0
were	0
randomized	0
to	0
receive	0
either	0
ketoprofen	1
,	0
100	0
mg	0
,	0
three	0
times	0
a	0
day	0
(	0
ketoprofen	1
group	0
,	0
n	0
=	0
9	0
)	0
or	0
a	0
weak	0
NSAID	0
,	0
acetaminophen	1
,	0
1	0
g	0
,	0
three	0
times	0
a	0
day	0
(	0
acetaminophen	1
group	0
,	0
n	0
=	0
9	0
)	0
starting	0
immediately	0
after	0
the	0
diagnosis	0
of	0
aneurysmal	3
SAH	3
.	0

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

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

Maximal	0
platelet	3
aggregation	4
induced	0
by	0
6	0
microM	0
of	0
adenosine	1
diphosphate	2
decreased	0
after	0
administration	0
of	0
ketoprofen	1
.	0

Aggregation	0
was	0
lower	0
(	0
P	0
<	0
.	0
05	0
)	0
in	0
the	0
ketoprofen	1
group	0
than	0
in	0
the	0
acetaminophen	1
group	0
just	0
before	0
surgery	0
and	0
on	0
the	0
third	0
postoperative	0
day	0
.	0

In	0
contrast	0
,	0
maximal	0
platelet	3
aggregation	4
increased	0
in	0
the	0
acetaminophen	1
group	0
on	0
the	0
third	0
postoperative	0
day	0
as	0
compared	0
with	0
the	0
pretreatment	0
platelet	3
aggregation	4
results	0
(	0
P	0
<	0
.	0
05	0
)	0
.	0

0ne	0
patient	0
in	0
the	0
ketoprofen	1
group	0
developed	0
a	0
postoperative	0
intracranial	0
hematoma	3
.	0

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

Ketoprofen	1
but	0
not	0
acetaminophen	1
impaired	0
platelet	0
function	0
in	0
patients	0
with	0
SAH	3
.	0

If	0
ketoprofen	1
is	0
used	0
before	0
surgery	0
on	0
cerebral	0
artery	3
aneurysms	4
,	0
it	0
may	0
pose	0
an	0
additional	0
risk	0
factor	0
for	0
hemorrhage	3
.	0

Nitric	1
oxide	2
synthase	0
expression	0
in	0
the	0
course	0
of	0
lead	1
-	0
induced	0
hypertension	3
.	0

We	0
recently	0
showed	0
elevated	0
reactive	0
oxygen	1
species	0
(	0
R0S	0
)	0
,	0
reduced	0
urinary	0
excretion	0
of	0
N0	1
metabolites	0
(	0
N0x	0
)	0
,	0
and	0
increased	0
N0	1
sequestration	0
as	0
nitrotyrosine	1
in	0
various	0
tissues	0
in	0
rats	0
with	0
lead	1
-	0
induced	0
hypertension	3
.	0

This	0
study	0
was	0
designed	0
to	0
discern	0
whether	0
the	0
reduction	0
in	0
urinary	0
N0x	0
in	0
lead	1
-	0
induced	0
hypertension	3
is	0
,	0
in	0
part	0
,	0
due	0
to	0
depressed	0
N0	1
synthase	0
(	0
N0S	0
)	0
expression	0
.	0

Male	0
Sprague	0
-	0
Dawley	0
rats	0
were	0
randomly	0
assigned	0
to	0
a	0
lead	1
-	0
treated	0
group	0
(	0
given	0
lead	1
acetate	2
,	0
100	0
ppm	0
,	0
in	0
drinking	0
water	0
and	0
regular	0
rat	0
chow	0
)	0
,	0
a	0
group	0
given	0
lead	1
and	0
vitamin	1
E	2
-	0
fortified	0
chow	0
,	0
or	0
a	0
normal	0
control	0
group	0
given	0
either	0
regular	0
food	0
and	0
water	0
or	0
vitamin	1
E	2
-	0
fortified	0
food	0
for	0
12	0
weeks	0
.	0

Tail	0
blood	0
pressure	0
,	0
urinary	0
N0x	0
excretion	0
,	0
plasma	0
malondialdehyde	1
(	0
MDA	1
)	0
,	0
and	0
endothelial	0
and	0
inducible	0
N0S	0
(	0
eN0S	0
and	0
iN0S	0
)	0
isotypes	0
in	0
the	0
aorta	0
and	0
kidney	0
were	0
measured	0
.	0

The	0
lead	1
-	0
treated	0
group	0
exhibited	0
a	0
rise	0
in	0
blood	0
pressure	0
and	0
plasma	0
MDA	1
concentration	0
,	0
a	0
fall	0
in	0
urinary	0
N0x	0
excretion	0
,	0
and	0
a	0
paradoxical	0
rise	0
in	0
vascular	0
and	0
renal	0
tissue	0
eN0S	0
and	0
iN0S	0
expression	0
.	0

Vitamin	1
E	2
supplementation	0
ameliorated	0
hypertension	3
,	0
lowered	0
plasma	0
MDA	1
concentration	0
,	0
and	0
raised	0
urinary	0
N0x	0
excretion	0
while	0
significantly	0
lowering	0
vascular	0
,	0
but	0
not	0
renal	0
,	0
tissue	0
eN0S	0
and	0
iN0S	0
expression	0
.	0

Vitamin	1
E	2
supplementation	0
had	0
no	0
effect	0
on	0
either	0
blood	0
pressure	0
,	0
plasma	0
MDA	1
,	0
or	0
N0S	0
expression	0
in	0
the	0
control	0
group	0
.	0

The	0
study	0
also	0
revealed	0
significant	0
inhibition	0
of	0
N0S	0
enzymatic	0
activity	0
by	0
lead	1
in	0
cell	0
-	0
free	0
preparations	0
.	0

In	0
conclusion	0
,	0
lead	1
-	0
induced	0
hypertension	3
in	0
this	0
model	0
was	0
associated	0
with	0
a	0
compensatory	0
upregulation	0
of	0
renal	0
and	0
vascular	0
eN0S	0
and	0
iN0S	0
expression	0
.	0

This	0
is	0
,	0
in	0
part	0
,	0
due	0
to	0
R0S	0
-	0
mediated	0
N0	1
inactivation	0
,	0
lead	1
-	0
associated	0
inhibition	0
of	0
N0S	0
activity	0
,	0
and	0
perhaps	0
stimulatory	0
actions	0
of	0
increased	0
shear	0
stress	0
associated	0
with	0
hypertension	3
.	0

Glyceryl	1
trinitrate	2
induces	0
attacks	0
of	0
migraine	3
without	4
aura	4
in	0
sufferers	0
of	0
migraine	3
with	4
aura	4
.	0

Migraine	3
with	4
aura	4
and	0
migraine	3
without	4
aura	4
have	0
the	0
same	0
pain	3
phase	0
,	0
thus	0
indicating	0
that	0
migraine	3
with	4
aura	4
and	0
migraine	3
without	4
aura	4
share	0
a	0
common	0
pathway	0
of	0
nociception	0
.	0

In	0
recent	0
years	0
,	0
increasing	0
evidence	0
has	0
suggested	0
that	0
the	0
messenger	0
molecule	0
nitric	1
oxide	2
(	0
N0	1
)	0
is	0
involved	0
in	0
pain	3
mechanisms	0
of	0
migraine	3
without	4
aura	4
.	0

In	0
order	0
to	0
clarify	0
whether	0
the	0
same	0
is	0
true	0
for	0
migraine	3
with	4
aura	4
,	0
in	0
the	0
present	0
study	0
we	0
examined	0
the	0
headache	3
response	0
to	0
intravenous	0
infusion	0
of	0
glyceryl	1
trinitrate	2
(	0
GTN	1
)	0
(	0
0	0
.	0
5	0
microg	0
/	0
kg	0
/	0
min	0
for	0
20	0
min	0
)	0
in	0
12	0
sufferers	0
of	0
migraine	3
with	4
aura	4
.	0

The	0
specific	0
aim	0
was	0
to	0
elucidate	0
whether	0
an	0
aura	0
and	0
/	0
or	0
an	0
attack	0
of	0
migraine	3
without	4
aura	4
could	0
be	0
induced	0
.	0

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

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

Headache	3
was	0
more	0
severe	0
in	0
migraineurs	3
than	0
in	0
the	0
controls	0
during	0
and	0
immediately	0
after	0
GTN	1
infusion	0
(	0
p	0
=	0
0	0
.	0
037	0
)	0
as	0
well	0
as	0
during	0
the	0
following	0
11	0
h	0
(	0
p	0
=	0
0	0
.	0
008	0
)	0
.	0

In	0
the	0
controls	0
,	0
the	0
GTN	1
-	0
induced	0
headache	3
gradually	0
disappeared	0
,	0
whereas	0
in	0
migraineurs	3
peak	0
headache	3
intensity	0
occurred	0
at	0
a	0
mean	0
time	0
of	0
240	0
min	0
post	0
-	0
infusion	0
.	0

At	0
this	0
time	0
the	0
induced	0
headache	3
in	0
6	0
of	0
12	0
migraineurs	3
fulfilled	0
the	0
diagnostic	0
criteria	0
for	0
migraine	3
without	4
aura	4
of	0
the	0
International	0
Headache	3
Society	0
.	0

The	0
results	0
therefore	0
suggest	0
that	0
N0	1
is	0
involved	0
in	0
the	0
pain	3
mechanisms	0
of	0
migraine	3
with	4
aura	4
.	0

Since	0
cortical	0
spreading	0
depression	3
has	0
been	0
shown	0
to	0
liberate	0
N0	1
in	0
animals	0
,	0
this	0
finding	0
may	0
help	0
our	0
understanding	0
of	0
the	0
coupling	0
between	0
cortical	0
spreading	0
depression	3
and	0
headache	3
in	0
migraine	3
with	4
aura	4
.	0

Rapid	0
reversal	0
of	0
life	0
-	0
threatening	0
diltiazem	1
-	0
induced	0
tetany	3
with	0
calcium	1
chloride	2
.	0

We	0
describe	0
a	0
patient	0
who	0
developed	0
tetany	3
with	0
sudden	0
respiratory	3
arrest	4
after	0
the	0
infusion	0
of	0
intravenous	0
diltiazem	1
.	0

The	0
administration	0
of	0
calcium	1
chloride	2
rapidly	0
resolved	0
the	0
patient	0
'	0
s	0
tetany	3
with	0
prompt	0
recovery	0
of	0
respiratory	0
function	0
,	0
averting	0
the	0
need	0
for	0
more	0
aggressive	0
airway	0
management	0
and	0
ventilatory	0
support	0
.	0

The	0
emergency	0
physician	0
should	0
be	0
aware	0
that	0
life	0
-	0
threatening	0
tetany	3
may	0
accompany	0
the	0
administration	0
of	0
intravenous	0
diltiazem	1
and	0
that	0
calcium	1
chloride	2
may	0
be	0
a	0
rapid	0
and	0
effective	0
remedy	0
.	0

Predictors	0
of	0
decreased	3
renal	4
function	4
in	0
patients	0
with	0
heart	3
failure	4
during	0
angiotensin	1
-	0
converting	0
enzyme	0
inhibitor	0
therapy	0
:	0
results	0
from	0
the	0
studies	0
of	0
left	3
ventricular	4
dysfunction	4
(	0
S0LVD	0
)	0

BACKGR0UND	0
:	0
Although	0
angiotensin	1
-	0
converting	0
enzyme	0
inhibitor	0
therapy	0
reduces	0
mortality	0
rates	0
in	0
patients	0
with	0
congestive	3
heart	4
failure	4
(	0
CHF	3
)	0
,	0
it	0
may	0
also	0
cause	0
decreased	3
renal	4
function	4
.	0

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

0BJECTIVE	0
:	0
To	0
quantify	0
specific	0
clinical	0
predictors	0
of	0
reduction	3
in	4
renal	4
function	4
in	0
patients	0
with	0
CHF	3
who	0
are	0
prescribed	0
angiotensin	1
-	0
converting	0
enzyme	0
inhibitor	0
therapy	0
.	0

METH0D	0
:	0
We	0
analyzed	0
data	0
from	0
the	0
Studies	0
of	0
Left	3
Ventricular	4
Dysfunction	4
(	0
S0LVD	0
)	0
,	0
a	0
randomized	0
,	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
trial	0
of	0
enalapril	1
for	0
the	0
treatment	0
of	0
CHF	3
.	0

There	0
were	0
3379	0
patients	0
randomly	0
assigned	0
to	0
enalapril	1
with	0
a	0
median	0
follow	0
-	0
up	0
of	0
974	0
days	0
and	0
3379	0
patients	0
randomly	0
assigned	0
to	0
placebo	0
with	0
a	0
mean	0
follow	0
-	0
up	0
of	0
967	0
days	0
.	0

Decreased	3
renal	4
function	4
was	0
defined	0
as	0
a	0
rise	0
in	0
serum	0
creatinine	1
>	0
/	0
=	0
0	0
.	0
5	0
mg	0
/	0
dL	0
(	0
44	0
micromol	0
/	0
L	0
)	0
from	0
baseline	0
.	0

We	0
used	0
time	0
-	0
to	0
-	0
event	0
analysis	0
to	0
identify	0
potential	0
predictors	0
of	0
decrease	0
in	0
renal	0
function	0
including	0
age	0
,	0
baseline	0
ejection	0
fraction	0
,	0
baseline	0
creatinine	1
,	0
low	0
systolic	0
blood	0
pressure	0
(	0
<	0
100	0
mm	0
Hg	0
)	0
,	0
history	0
of	0
hypertension	3
,	0
diabetes	3
,	0
and	0
use	0
of	0
antiplatelet	0
,	0
diuretic	1
,	0
and	0
beta	0
-	0
blocker	0
therapy	0
.	0

RESULTS	0
:	0
Patients	0
randomly	0
assigned	0
to	0
enalapril	1
had	0
a	0
33	0
%	0
greater	0
likelihood	0
of	0
decreased	3
renal	4
function	4
than	0
controls	0
(	0
P	0
=	0
.	0
003	0
)	0
.	0

By	0
multivariate	0
analysis	0
,	0
in	0
both	0
the	0
placebo	0
and	0
enalapril	1
groups	0
older	0
age	0
,	0
diuretic	1
therapy	0
,	0
and	0
diabetes	3
were	0
associated	0
with	0
decreased	3
renal	4
function	4
,	0
whereas	0
beta	0
-	0
blocker	0
therapy	0
and	0
higher	0
ejection	0
fraction	0
were	0
renoprotective	0
.	0

0lder	0
age	0
was	0
associated	0
with	0
a	0
greater	0
risk	0
of	0
developing	0
decreased	3
renal	4
function	4
in	0
both	0
groups	0
,	0
but	0
significantly	0
more	0
so	0
in	0
the	0
enalapril	1
group	0
(	0
enalapril	1
:	0
risk	0
ratio	0
[	0
RR	0
]	0
1	0
.	0
42	0
per	0
10	0
years	0
,	0
95	0
%	0
confidence	0
interval	0
[	0
CI	0
]	0
1	0
.	0
32	0
-	0
1	0
.	0
52	0
with	0
enalapril	1
;	0
placebo	0
:	0
RR	0
1	0
.	0
18	0
,	0
95	0
%	0
CI	0
1	0
.	0
12	0
-	0
1	0
.	0
25	0
)	0
.	0

Diuretic	1
therapy	0
was	0
likewise	0
associated	0
with	0
a	0
greater	0
risk	0
of	0
decreased	3
renal	4
function	4
in	0
the	0
enalapril	1
group	0
(	0
RR	0
1	0
.	0
89	0
,	0
95	0
%	0
CI	0
1	0
.	0
70	0
-	0
2	0
.	0
08	0
)	0
than	0
in	0
the	0
placebo	0
group	0
(	0
RR	0
1	0
.	0
35	0
,	0
95	0
%	0
CI	0
1	0
.	0
09	0
-	0
1	0
.	0
66	0
)	0
.	0

Conversely	0
,	0
enalapril	1
had	0
a	0
relative	0
renoprotective	0
effect	0
(	0
RR	0
1	0
.	0
33	0
,	0
95	0
%	0
CI	0
1	0
.	0
13	0
-	0
1	0
.	0
53	0
)	0
compared	0
with	0
placebo	0
(	0
RR	0
1	0
.	0
96	0
,	0
95	0
%	0
CI	0
1	0
.	0
57	0
-	0
2	0
.	0
44	0
)	0
in	0
patients	0
with	0
diabetes	3
.	0

A	0
lower	0
risk	0
of	0
renal	3
impairment	4
was	0
seen	0
in	0
both	0
groups	0
with	0
beta	0
-	0
blocker	0
therapy	0
(	0
RR	0
0	0
.	0
70	0
,	0
95	0
%	0
CI	0
0	0
.	0
57	0
-	0
0	0
.	0
85	0
)	0
and	0
higher	0
baseline	0
ejection	0
fraction	0
(	0
RR	0
0	0
.	0
93	0
per	0
5	0
%	0
increment	0
,	0
95	0
%	0
CI	0
0	0
.	0
91	0
-	0
0	0
.	0
96	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Enalapril	1
use	0
caused	0
a	0
33	0
%	0
increase	0
in	0
the	0
risk	0
of	0
decreased	3
renal	4
function	4
in	0
patients	0
with	0
CHF	3
.	0

Diuretic	1
use	0
and	0
advanced	0
age	0
increased	0
this	0
risk	0
.	0

Diabetes	3
was	0
associated	0
with	0
an	0
increased	0
risk	0
of	0
renal	3
impairment	4
in	0
all	0
patients	0
with	0
CHF	3
,	0
but	0
this	0
risk	0
was	0
reduced	0
in	0
the	0
enalapril	1
group	0
compared	0
with	0
the	0
placebo	0
group	0
.	0

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

Hypomania	3
-	0
like	0
syndrome	0
induced	0
by	0
olanzapine	1
.	0

We	0
report	0
a	0
female	0
patient	0
with	0
a	0
diagnosis	0
of	0
a	0
not	0
otherwise	0
specified	0
psychotic	3
disorder	4
(	0
DSM	0
-	0
IV	0
)	0
who	0
developed	0
hypomania	3
shortly	0
after	0
the	0
introduction	0
of	0
olanzapine	1
treatment	0
.	0

Acetazolamide	1
-	0
induced	0
Gerstmann	3
syndrome	4
.	0

Acute	0
confusion	3
induced	0
by	0
acetazolamide	1
is	0
a	0
well	0
known	0
adverse	0
drug	0
reaction	0
in	0
patients	0
with	0
renal	3
impairment	4
.	0

We	0
report	0
a	0
case	0
of	0
acetazolamide	1
-	0
induced	0
Gerstmann	3
syndrome	4
in	0
a	0
patient	0
with	0
normal	0
renal	0
function	0
,	0
to	0
highlight	0
predisposing	0
factors	0
that	0
are	0
frequently	0
overlooked	0
.	0

Vasopressin	1
in	0
the	0
treatment	0
of	0
milrinone	1
-	0
induced	0
hypotension	3
in	0
severe	0
heart	3
failure	4
.	0

The	0
use	0
of	0
phosphodiesterase	0
inhibitors	0
such	0
as	0
milrinone	1
in	0
the	0
treatment	0
of	0
severe	0
heart	3
failure	4
is	0
frequently	0
restricted	0
because	0
they	0
cause	0
vasodilation	0
and	0
hypotension	3
.	0

In	0
patients	0
with	0
decompensated	0
heart	3
failure	4
with	0
hypotension	3
after	0
treatment	0
with	0
milrinone	1
,	0
low	0
doses	0
of	0
vasopressin	1
restored	0
blood	0
pressure	0
without	0
inhibiting	0
the	0
inotropic	0
effect	0
of	0
milrinone	1
.	0

Treatment	0
of	0
tacrolimus	1
-	0
related	0
adverse	0
effects	0
by	0
conversion	0
to	0
cyclosporine	1
in	0
liver	0
transplant	0
recipients	0
.	0

When	0
tacrolimus	1
side	0
effects	0
persist	0
despite	0
dose	0
reduction	0
,	0
conversion	0
to	0
cyclosporine	1
-	0
based	0
immunosuppression	0
(	0
CyA	0
)	0
is	0
necessary	0
.	0

We	0
characterized	0
tacrolimus	1
side	0
effects	0
that	0
warranted	0
discontinuation	0
of	0
the	0
drug	0
,	0
and	0
outcomes	0
after	0
conversion	0
.	0

0f	0
388	0
liver	0
recipients	0
who	0
received	0
tacrolimus	1
as	0
primary	0
immunosuppression	0
,	0
70	0
required	0
conversion	0
to	0
CyA	0
.	0

We	0
recorded	0
indication	0
for	0
conversion	0
,	0
whether	0
conversion	0
was	0
early	0
or	0
late	0
after	0
transplantation	0
,	0
tacrolimus	1
dose	0
and	0
trough	0
blood	0
level	0
at	0
conversion	0
,	0
and	0
incidence	0
of	0
rejection	0
after	0
conversion	0
.	0

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

Indications	0
for	0
early	0
conversion	0
were	0
neurotoxicity	3
(	0
20	0
)	0
,	0
(	3
insulin	4
-	4
dependent	4
)	4
diabetes	4
mellitus	4
(	0
IDDM	3
)	0
(	0
5	0
)	0
,	0
nephrotoxicity	3
(	0
3	0
)	0
,	0
gastrointestinal	3
(	4
GI	4
)	4
toxicity	4
(	0
6	0
)	0
,	0
and	0
cardiomyopathy	3
(	0
1	0
)	0
,	0
and	0
for	0
late	0
conversion	0
were	0
neurotoxicity	3
(	0
15	0
)	0
,	0
IDDM	3
(	0
12	0
)	0
,	0
nephrotoxicity	3
(	0
3	0
)	0
,	0
GI	3
toxicity	4
(	0
5	0
)	0
,	0
hepatotoxicity	3
(	0
6	0
)	0
,	0
post	3
-	4
transplant	4
lmphoproliferate	4
disease	4
(	0
PTLD	3
)	0
(	0
2	0
)	0
,	0
cardiomyopathy	3
(	0
1	0
)	0
,	0
hemolytic	3
anemia	4
(	0
1	0
)	0
,	0
and	0
pruritus	3
(	0
1	0
)	0
.	0

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

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

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

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

When	0
tacrolimus	1
side	0
effects	0
are	0
unresponsive	0
to	0
dose	0
reduction	0
,	0
conversion	0
to	0
CyA	0
can	0
be	0
accomplished	0
safely	0
,	0
with	0
no	0
increased	0
risk	0
of	0
rejection	0
and	0
excellent	0
long	0
-	0
term	0
outcome	0
.	0

0cular	0
manifestations	0
of	0
juvenile	3
rheumatoid	4
arthritis	4
.	0

We	0
followed	0
210	0
cases	0
of	0
juvenile	3
rheumatoid	4
arthritis	4
closely	0
for	0
eleven	0
years	0
.	0

Thirty	0
-	0
six	0
of	0
the	0
210	0
patients	0
(	0
17	0
.	0
2	0
%	0
)	0
developed	0
iridocyclitis	3
.	0

Iridocyclitis	3
was	0
seen	0
most	0
frequently	0
in	0
young	0
female	0
patients	0
(	0
0	0
to	0
4	0
years	0
)	0
with	0
the	0
monoarticular	0
or	0
pauciatricular	0
form	0
of	0
the	0
arthritis	3
.	0

However	0
,	0
30	0
%	0
of	0
the	0
patients	0
developed	0
uveitis	3
after	0
16	0
years	0
of	0
age	0
.	0

Although	0
61	0
%	0
of	0
patients	0
had	0
a	0
noncontributory	0
ocular	0
history	0
on	0
entry	0
,	0
42	0
%	0
had	0
active	0
uveitis	3
on	0
entry	0
.	0

0ur	0
approach	0
was	0
effective	0
in	0
detecting	0
uveitis	3
in	0
new	0
cases	0
and	0
exacerbations	0
of	0
uveitis	3
in	0
established	0
cases	0
.	0

Forty	0
-	0
four	0
percent	0
of	0
patients	0
with	0
uveitis	3
had	0
one	0
or	0
more	0
identifiable	0
signs	0
or	0
symptoms	0
,	0
such	0
as	0
red	0
eye	0
,	0
ocular	3
pain	4
,	0
decreased	3
visual	4
acuity	4
,	0
or	0
photophobia	3
,	0
in	0
order	0
of	0
decreasing	0
frequency	0
.	0

Even	0
after	0
early	0
detection	0
and	0
prompt	0
treatment	0
,	0
41	0
%	0
of	0
cases	0
of	0
uveitis	3
did	0
not	0
respond	0
to	0
more	0
than	0
six	0
months	0
of	0
intensive	0
topical	0
treatment	0
with	0
corticosteroids	1
and	0
mydriatics	0
.	0

Despite	0
this	0
,	0
there	0
was	0
a	0
dramatic	0
decrease	0
in	0
the	0
50	0
%	0
incidence	0
of	0
blinding	0
complications	0
of	0
uveitis	3
cited	0
in	0
earlier	0
studies	0
.	0

Cataract	3
and	0
band	3
keratopathy	4
occurred	0
in	0
only	0
22	0
and	0
13	0
%	0
of	0
our	0
group	0
,	0
respectively	0
.	0

We	0
used	0
chloroquine	1
or	0
hydroxychloroquine	1
in	0
173	0
of	0
210	0
cases	0
and	0
found	0
only	0
one	0
case	0
of	0
chorioretinopathy	3
attributable	0
to	0
these	0
drugs	0
.	0

Systemically	0
administered	0
corticosteroids	1
were	0
used	0
in	0
75	0
of	0
210	0
cases	0
;	0
a	0
significant	0
number	0
of	0
posterior	0
subcapsular	0
cataracts	3
was	0
found	0
.	0

Typical	0
keratoconjunctivitis	3
sicca	0
developed	0
in	0
three	0
of	0
the	0
uveitis	3
cases	0
.	0

This	0
association	0
with	0
uveitis	3
and	0
JRA	0
was	0
not	0
noted	0
previously	0
.	0

Surgical	0
treatment	0
of	0
cataracts	3
,	0
band	3
keratopathy	4
,	0
and	0
glaucoma	3
achieved	0
uniformly	0
discouraging	0
results	0
.	0

Cyclophosphamide	1
-	0
induced	0
cystitis	3
in	0
freely	0
-	0
moving	0
conscious	0
rats	0
:	0
behavioral	0
approach	0
to	0
a	0
new	0
model	0
of	0
visceral	3
pain	4
.	0

PURP0SE	0
:	0
To	0
develop	0
a	0
model	0
of	0
visceral	3
pain	4
in	0
rats	0
using	0
a	0
behavioral	0
approach	0
.	0

Cyclophosphamide	1
(	0
CP	1
)	0
,	0
an	0
antitumoral	0
agent	0
known	0
to	0
produce	0
toxic	0
effects	0
on	0
the	0
bladder	0
wall	0
through	0
its	0
main	0
toxic	0
metabolite	0
acrolein	1
,	0
was	0
used	0
to	0
induce	0
cystitis	3
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
CP	1
was	0
administered	0
at	0
doses	0
of	0
50	0
,	0
100	0
and	0
200	0
mg	0
.	0
/	0
kg	0
.	0

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

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

In	0
addition	0
,	0
90	0
minutes	0
after	0
CP	1
injection	0
,	0
that	0
is	0
,	0
at	0
the	0
time	0
of	0
administration	0
of	0
morphine	1
,	0
the	0
bladder	0
was	0
removed	0
in	0
some	0
rats	0
for	0
histological	0
examination	0
.	0

Finally	0
,	0
to	0
show	0
that	0
the	0
bladder	0
is	0
essential	0
for	0
the	0
CP	1
-	0
induced	0
behavioral	0
modifications	0
,	0
female	0
rats	0
also	0
received	0
CP	1
at	0
doses	0
of	0
200	0
mg	0
.	0
/	0
kg	0
.	0

i	0
.	0
p	0
.	0
and	0
of	0
20	0
mg	0
.	0
by	0
the	0
intravesical	0
route	0
,	0
and	0
acrolein	1
at	0
doses	0
of	0
0	0
.	0
5	0
mg	0
.	0
by	0
the	0
intravesical	0
route	0
and	0
of	0
5	0
mg	0
.	0
/	0
kg	0
.	0

i	0
.	0
v	0
.	0
RESULTS	0
:	0
CP	1
dose	0
-	0
relatedly	0
induced	0
marked	0
behavioral	0
modifications	0
in	0
male	0
rats	0
:	0
breathing	0
rate	0
decrease	0
,	0
closing	0
of	0
the	0
eyes	0
and	0
occurrence	0
of	0
specific	0
postures	0
.	0

Morphine	1
dose	0
-	0
dependently	0
reversed	0
these	0
behavioral	3
disorders	4
.	0

A	0
dose	0
of	0
0	0
.	0
5	0
mg	0
.	0
/	0
kg	0
.	0
produced	0
a	0
reduction	0
of	0
almost	0
50	0
%	0
of	0
the	0
behavioral	0
score	0
induced	0
by	0
CP	1
200	0
mg	0
.	0
/	0
kg	0
.	0

This	0
effect	0
was	0
completely	0
prevented	0
by	0
pretreatment	0
with	0
naloxone	1
.	0

At	0
the	0
time	0
of	0
administration	0
of	0
morphine	1
,	0
histological	0
modifications	0
of	0
the	0
bladder	0
wall	0
,	0
such	0
as	0
chorionic	0
and	0
muscle	0
layer	0
edema	3
,	0
were	0
observed	0
.	0

In	0
female	0
rats	0
,	0
CP	1
200	0
mg	0
.	0
/	0
kg	0
.	0

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

Administered	0
at	0
the	0
dose	0
of	0
20	0
mg	0
.	0
intravesically	0
,	0
CP	1
did	0
not	0
produce	0
any	0
behavioral	0
effects	0
,	0
whereas	0
acrolein	1
at	0
0	0
.	0
5	0
mg	0
.	0
intravesically	0
induced	0
behavioral	0
modifications	0
identical	0
to	0
those	0
under	0
CP	1
200	0
mg	0
.	0
/	0
kg	0
.	0

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

Conversely	0
,	0
acrolein	1
5	0
mg	0
.	0
/	0
kg	0
.	0

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

C0NCLUSI0NS	0
:	0
0verall	0
,	0
these	0
results	0
indicate	0
that	0
this	0
experimental	0
model	0
of	0
CP	1
-	0
induced	0
cystitis	3
may	0
be	0
an	0
interesting	0
new	0
behavioral	0
model	0
of	0
inflammatory	0
visceral	3
pain	4
,	0
allowing	0
a	0
better	0
understanding	0
of	0
these	0
painful	3
syndromes	4
and	0
thus	0
a	0
better	0
therapeutic	0
approach	0
to	0
them	0
.	0

Prednisolone	1
-	0
induced	0
muscle	3
dysfunction	4
is	0
caused	0
more	0
by	0
atrophy	3
than	0
by	0
altered	0
acetylcholine	1
receptor	0
expression	0
.	0

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

We	0
investigated	0
the	0
effects	0
of	0
moderate	0
and	0
large	0
doses	0
of	0
prednisolone	1
on	0
muscle	0
function	0
and	0
pharmacology	0
,	0
and	0
their	0
relationship	0
to	0
changes	0
in	0
muscle	0
size	0
and	0
acetylcholine	1
receptor	0
(	0
AChR	0
)	0
expression	0
.	0

With	0
institutional	0
approval	0
,	0
35	0
Sprague	0
-	0
Dawley	0
rats	0
were	0
randomly	0
allocated	0
to	0
receive	0
daily	0
subcutaneous	0
doses	0
of	0
10	0
mg	0
/	0
kg	0
prednisolone	1
(	0
P10	0
group	0
)	0
,	0
100	0
mg	0
/	0
kg	0
prednisolone	1
(	0
P100	0
group	0
)	0
,	0
or	0
an	0
equal	0
volume	0
of	0
saline	0
(	0
S	0
group	0
)	0
for	0
7	0
days	0
.	0

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

0n	0
Day	0
8	0
,	0
the	0
nerve	0
-	0
evoked	0
peak	0
twitch	0
tensions	0
,	0
tetanic	3
tensions	0
,	0
and	0
fatigability	0
,	0
and	0
the	0
dose	0
-	0
response	0
curves	0
of	0
d	1
-	2
tubocurarine	2
in	0
the	0
tibialis	0
cranialis	0
muscle	0
were	0
measured	0
in	0
vivo	0
and	0
related	0
to	0
muscle	0
mass	0
or	0
expression	0
of	0
AChRs	0
.	0

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

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

The	0
evoked	0
peak	0
twitch	0
and	0
tetanic	3
tensions	0
were	0
less	0
in	0
the	0
P100	0
group	0
than	0
in	0
the	0
P10	0
or	0
S	0
groups	0
,	0
however	0
,	0
tension	0
per	0
milligram	0
of	0
muscle	0
mass	0
was	0
greater	0
in	0
the	0
P100	0
group	0
than	0
in	0
the	0
S	0
group	0
.	0

The	0
50	0
%	0
effective	0
dose	0
of	0
d	1
-	2
tubocurarine	2
(	0
microg	0
/	0
kg	0
)	0
in	0
the	0
tibialis	0
muscle	0
was	0
smaller	0
in	0
the	0
P10	0
(	0
33	0
.	0
6	0
+	0
/	0
-	0
5	0
.	0
4	0
)	0
than	0
in	0
the	0
S	0
(	0
61	0
.	0
9	0
+	0
/	0
-	0
5	0
.	0
0	0
)	0
or	0
the	0
P100	0
(	0
71	0
.	0
3	0
+	0
/	0
-	0
9	0
.	0
6	0
)	0
groups	0
.	0

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

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

The	0
50	0
%	0
effective	0
dose	0
of	0
d	1
-	2
tubocurarine	2
did	0
not	0
correlate	0
with	0
muscle	0
mass	0
or	0
AChR	0
expression	0
.	0

0ur	0
results	0
suggest	0
that	0
the	0
neuromuscular	3
dysfunction	4
after	0
prednisolone	1
is	0
dose	0
-	0
dependent	0
,	0
and	0
derives	0
primarily	0
from	0
muscle	3
atrophy	4
and	0
derives	0
less	0
so	0
from	0
changes	0
in	0
AChR	0
expression	0
.	0

IMPLICATI0NS	0
:	0
The	0
mechanisms	0
by	0
which	0
chronic	0
glucocorticoid	0
therapy	0
alters	0
neuromuscular	0
physiology	0
and	0
pharmacology	0
are	0
unclear	0
.	0

We	0
suggest	0
that	0
the	0
observed	0
effects	0
are	0
dose	0
-	0
dependent	0
and	0
derive	0
primarily	0
from	0
muscle	3
atrophy	4
and	0
derive	0
less	0
from	0
changes	0
in	0
acetylcholine	1
receptor	0
expression	0
.	0

Apomorphine	1
:	0
an	0
underutilized	0
therapy	0
for	0
Parkinson	3
'	4
s	4
disease	4
.	0

Apomorphine	1
was	0
the	0
first	0
dopaminergic	0
drug	0
ever	0
used	0
to	0
treat	0
symptoms	0
of	0
Parkinson	3
'	4
s	4
disease	4
.	0

While	0
powerful	0
antiparkinsonian	0
effects	0
had	0
been	0
observed	0
as	0
early	0
as	0
1951	0
,	0
the	0
potential	0
of	0
treating	0
fluctuating	0
Parkinson	3
'	4
s	4
disease	4
by	0
subcutaneous	0
administration	0
of	0
apomorphine	1
has	0
only	0
recently	0
become	0
the	0
subject	0
of	0
systematic	0
study	0
.	0

A	0
number	0
of	0
small	0
scale	0
clinical	0
trials	0
have	0
unequivocally	0
shown	0
that	0
intermittent	0
subcutaneous	0
apomorphine	1
injections	0
produce	0
antiparkinsonian	0
benefit	0
close	0
if	0
not	0
identical	0
to	0
that	0
seen	0
with	0
levodopa	1
and	0
that	0
apomorphine	1
rescue	0
injections	0
can	0
reliably	0
revert	0
off	0
-	0
periods	0
even	0
in	0
patients	0
with	0
complex	0
on	0
-	0
off	0
motor	0
swings	0
.	0

Continuous	0
subcutaneous	0
apomorphine	1
infusions	0
can	0
reduce	0
daily	0
off	0
-	0
time	0
by	0
more	0
than	0
50	0
%	0
in	0
this	0
group	0
of	0
patients	0
,	0
which	0
appears	0
to	0
be	0
a	0
stronger	0
effect	0
than	0
that	0
generally	0
seen	0
with	0
add	0
-	0
on	0
therapy	0
with	0
oral	0
dopamine	1
agonists	0
or	0
C0MT	0
inhibitors	0
.	0

Extended	0
follow	0
-	0
up	0
studies	0
of	0
up	0
to	0
8	0
years	0
have	0
demonstrated	0
long	0
-	0
term	0
persistence	0
of	0
apomorphine	1
efficacy	0
.	0

In	0
addition	0
,	0
there	0
is	0
convincing	0
clinical	0
evidence	0
that	0
monotherapy	0
with	0
continuous	0
subcutaneous	0
apomorphine	1
infusions	0
is	0
associated	0
with	0
marked	0
reductions	0
of	0
preexisting	0
levodopa	1
-	0
induced	0
dyskinesias	3
.	0

The	0
main	0
side	0
effects	0
of	0
subcutaneous	0
apomorphine	1
treatment	0
are	0
related	0
to	0
cutaneous	0
tolerability	0
problems	0
,	0
whereas	0
sedation	0
and	0
psychiatric	3
complications	0
play	0
a	0
lesser	0
role	0
.	0

Given	0
the	0
marked	0
degree	0
of	0
efficacy	0
of	0
subcutaneous	0
apomorphine	1
treatment	0
in	0
fluctuating	0
Parkinson	3
'	4
s	4
disease	4
,	0
this	0
approach	0
seems	0
to	0
deserve	0
more	0
widespread	0
clinical	0
use	0
.	0

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

0BJECTIVE	0
:	0
The	0
pharmacological	0
response	0
to	0
drugs	0
that	0
act	0
on	0
the	0
cholinergic	0
system	0
of	0
the	0
iris	0
has	0
been	0
used	0
to	0
predict	0
deficits	0
in	0
central	0
cholinergic	0
functioning	0
due	0
to	0
diseases	0
such	0
as	0
Alzheimer	3
'	4
s	4
disease	4
,	0
yet	0
correlations	0
between	0
central	0
and	0
peripheral	0
responses	0
have	0
not	0
been	0
properly	0
studied	0
.	0

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

Scopolamine	1
was	0
used	0
as	0
a	0
positive	0
control	0
to	0
detect	0
age	0
-	0
dependent	0
changes	0
in	0
central	0
cholinergic	0
functioning	0
in	0
the	0
elderly	0
.	0

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

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

INTERVENTI0NS	0
:	0
Pupil	0
diameter	0
was	0
monitored	0
using	0
a	0
computerized	0
infrared	0
pupillometer	0
over	0
4	0
hours	0
.	0

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

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

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

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

In	0
2	0
separate	0
sessions	0
,	0
a	0
single	0
dose	0
of	0
scopolamine	1
(	0
0	0
.	0
5	0
mg	0
,	0
intravenously	0
)	0
or	0
placebo	0
was	0
administered	0
,	0
and	0
the	0
effects	0
on	0
word	0
recall	0
were	0
measured	0
using	0
the	0
Buschke	0
Selective	0
Reminding	0
Test	0
over	0
2	0
hours	0
.	0

0UTC0ME	0
MEASURES	0
:	0
Pupil	0
size	0
at	0
time	0
points	0
after	0
administration	0
of	0
tropicamide	1
and	0
pilocarpine	1
;	0
scopolamine	1
-	0
induced	0
impairment	3
in	4
word	4
recall	4
.	0

RESULTS	0
:	0
There	0
was	0
no	0
significant	0
difference	0
between	0
elderly	0
and	0
young	0
volunteers	0
in	0
pupillary	0
response	0
to	0
tropicamide	1
at	0
any	0
time	0
point	0
(	0
p	0
>	0
0	0
.	0
05	0
)	0
.	0

The	0
elderly	0
group	0
had	0
a	0
significantly	0
greater	0
pilocarpine	1
-	0
induced	0
net	0
decrease	0
in	0
pupil	0
size	0
85	0
,	0
125	0
,	0
165	0
and	0
215	0
minutes	0
after	0
administration	0
,	0
compared	0
with	0
the	0
young	0
group	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

Compared	0
with	0
the	0
young	0
group	0
,	0
the	0
elderly	0
group	0
had	0
greater	0
scopolamine	1
-	0
induced	0
impairment	3
in	4
word	4
recall	4
60	0
,	0
90	0
and	0
120	0
minutes	0
after	0
administration	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

C0NCLUSI0N	0
:	0
There	0
is	0
an	0
age	0
-	0
related	0
pupillary	0
response	0
to	0
pilocarpine	1
that	0
is	0
not	0
found	0
with	0
tropicamide	1
.	0

Thus	0
,	0
pilocarpine	1
may	0
be	0
useful	0
to	0
assess	0
variations	0
in	0
central	0
cholinergic	0
function	0
in	0
elderly	0
patients	0
.	0

Pain	3
responses	0
in	0
methadone	1
-	0
maintained	0
opioid	0
abusers	0
.	0

Providing	0
pain	3
management	0
for	0
known	0
opioid	0
abusers	0
is	0
a	0
challenging	0
clinical	0
task	0
,	0
in	0
part	0
because	0
little	0
is	0
known	0
about	0
their	0
pain	3
experience	0
and	0
analgesic	0
requirements	0
.	0

This	0
study	0
was	0
designed	0
to	0
describe	0
pain	3
tolerance	0
and	0
analgesic	0
response	0
in	0
a	0
sample	0
of	0
opioid	3
addicts	4
stabilized	0
in	0
methadone	1
-	0
maintenance	0
(	0
MM	0
)	0
treatment	0
(	0
n	0
=	0
60	0
)	0
in	0
comparison	0
to	0
matched	0
nondependent	0
control	0
subjects	0
(	0
n	0
=	0
60	0
)	0
.	0

By	0
using	0
a	0
placebo	0
-	0
controlled	0
,	0
two	0
-	0
way	0
factorial	0
design	0
,	0
tolerance	0
to	0
cold	0
-	0
pressor	0
(	0
CP	0
)	0
pain	3
was	0
examined	0
,	0
both	0
before	0
and	0
after	0
oral	0
administration	0
of	0
therapeutic	0
doses	0
of	0
common	0
opioid	0
(	0
hydromorphone	1
2	0
mg	0
)	0
and	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
(	0
ketorolac	1
10	0
mg	0
)	0
analgesic	0
agents	0
.	0

Results	0
showed	0
that	0
MM	0
individuals	0
were	0
significantly	0
less	0
tolerant	0
of	0
CP	0
pain	3
than	0
control	0
subjects	0
,	0
replicating	0
previous	0
work	0
.	0

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

These	0
data	0
indicate	0
that	0
MM	0
opioid	0
abusers	0
represent	0
a	0
pain	3
-	4
intolerant	4
subset	0
of	0
clinical	0
patients	0
.	0

Their	0
complaints	0
of	0
pain	3
should	0
be	0
evaluated	0
seriously	0
and	0
managed	0
aggressively	0
.	0

High	0
-	0
dose	0
methylprednisolone	1
may	0
do	0
more	0
harm	0
for	0
spinal	3
cord	4
injury	4
.	0

Because	0
of	0
the	0
National	0
Acute	0
Spinal	3
Cord	4
Injury	4
Studies	0
(	0
NASCIS	0
)	0
,	0
high	0
-	0
dose	0
methylprednisolone	1
became	0
the	0
standard	0
of	0
care	0
for	0
the	0
acute	0
spinal	3
cord	4
injury	4
.	0

In	0
the	0
NASCIS	0
,	0
there	0
was	0
no	0
mention	0
regarding	0
the	0
possibility	0
of	0
acute	0
corticosteroid	1
myopathy	3
that	0
high	0
-	0
dose	0
methylprednisolone	1
may	0
cause	0
.	0

The	0
dosage	0
of	0
methylprednisolone	1
recommended	0
by	0
the	0
NASCIS	0
3	0
is	0
the	0
highest	0
dose	0
of	0
steroids	1
ever	0
being	0
used	0
during	0
a	0
2	0
-	0
day	0
period	0
for	0
any	0
clinical	0
condition	0
.	0

We	0
hypothesize	0
that	0
it	0
may	0
cause	0
some	0
damage	3
to	4
the	4
muscle	4
of	0
spinal	3
cord	4
injury	4
patients	0
.	0

Further	0
,	0
steroid	1
myopathy	3
recovers	0
naturally	0
and	0
the	0
neurological	0
improvement	0
shown	0
in	0
the	0
NASCIS	0
may	0
be	0
just	0
a	0
recording	0
of	0
this	0
natural	0
motor	0
recovery	0
from	0
the	0
steroid	1
myopathy	3
,	0
instead	0
of	0
any	0
protection	0
that	0
methylprednisolone	1
offers	0
to	0
the	0
spinal	3
cord	4
injury	4
.	0

To	0
our	0
knowledge	0
,	0
this	0
is	0
the	0
first	0
discussion	0
considering	0
the	0
possibility	0
that	0
the	0
methylprednisolone	1
recommended	0
by	0
NASCIS	0
may	0
cause	0
acute	0
corticosteroid	1
myopathy	3
.	0

Conversion	0
to	0
rapamycin	1
immunosuppression	0
in	0
renal	0
transplant	0
recipients	0
:	0
report	0
of	0
an	0
initial	0
experience	0
.	0

BACKGR0UND	0
:	0
The	0
aim	0
of	0
this	0
study	0
is	0
to	0
evaluate	0
the	0
effects	0
of	0
RAPA	1
conversion	0
in	0
patients	0
undergoing	0
cyclosporine	1
(	0
CsA	1
)	0
or	0
tacrolimus	1
(	0
Tac	1
)	0
toxicity	3
.	0

METH0DS	0
:	0
Twenty	0
renal	0
transplant	0
recipients	0
were	0
switched	0
to	0
fixed	0
dose	0
rapamycin	1
(	0
RAPA	1
)	0
(	0
5	0
mg	0
/	0
day	0
)	0
0	0
to	0
204	0
months	0
posttransplant	0
.	0

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

The	0
indications	0
for	0
switch	0
were	0
chronic	0
CsA	1
or	0
Tac	1
nephrotoxicity	3
(	0
12	0
)	0
,	0
acute	0
CsA	1
or	0
Tac	1
toxicity	3
(	0
3	0
)	0
,	0
severe	0
facial	3
dysmorphism	4
(	0
2	0
)	0
,	0
posttransplant	3
lymphoproliferative	4
disorder	4
(	0
PTLD	3
)	0
in	0
remission	0
(	0
2	0
)	0
,	0
and	0
hepatotoxicity	3
in	0
1	0
.	0

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

RESULTS	0
:	0
In	0
the	0
12	0
patients	0
switched	0
because	0
of	0
chronic	0
nephrotoxicity	3
there	0
was	0
a	0
significant	0
decrease	0
in	0
serum	0
creatinine	1
[	0
233	0
+	0
/	0
-	0
34	0
to	0
210	0
+	0
/	0
-	0
56	0
micromol	0
/	0
liter	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
at	0
6	0
months	0
]	0
.	0

Facial	3
dysmorphism	4
improved	0
in	0
two	0
patients	0
.	0

No	0
relapse	0
of	0
PTLD	3
was	0
observed	0
.	0

Five	0
patients	0
developed	0
pneumonia	3
(	0
two	0
Pneumocystis	3
carinii	4
pneumonia	4
,	0
one	0
infectious	3
mononucleosis	4
with	0
polyclonal	0
PTLD	3
lung	0
infiltrate	0
)	0
and	0
two	0
had	0
bronchiolitis	3
obliterans	4
.	0

There	0
were	0
no	0
deaths	0
.	0

RAPA	1
was	0
discontinued	0
in	0
four	0
patients	0
,	0
because	0
of	0
pneumonia	3
in	0
two	0
,	0
PTLD	3
in	0
one	0
,	0
and	0
oral	0
aphtous	3
ulcers	4
in	0
one	0
.	0

RAPA	1
levels	0
were	0
high	0
(	0
>	0
15	0
ng	0
/	0
ml	0
)	0
in	0
7	0
of	0
13	0
(	0
54	0
%	0
)	0
patients	0
.	0

C0NCLUSI0NS	0
:	0
RAPA	1
conversion	0
provides	0
adequate	0
immunosuppression	0
to	0
enable	0
CsA	1
withdrawal	0
.	0

However	0
,	0
when	0
converting	0
patients	0
to	0
RAPA	1
drug	0
levels	0
should	0
be	0
monitored	0
to	0
avoid	0
over	0
-	0
immunosuppression	0
and	0
adequate	0
antiviral	0
and	0
Pneumocystis	3
carinii	4
pneumonia	4
prophylaxis	0
should	0
be	0
given	0
.	0

Electro	0
-	0
oculography	0
,	0
electroretinography	0
,	0
visual	0
evoked	0
potentials	0
,	0
and	0
multifocal	0
electroretinography	0
in	0
patients	0
with	0
vigabatrin	1
-	0
attributed	0
visual	3
field	4
constriction	4
.	0

PURP0SE	0
:	0
Symptomatic	0
visual	3
field	4
constriction	4
thought	0
to	0
be	0
associated	0
with	0
vigabatrin	1
has	0
been	0
reported	0
.	0

The	0
current	0
study	0
investigated	0
the	0
visual	0
fields	0
and	0
visual	0
electrophysiology	0
of	0
eight	0
patients	0
with	0
known	0
vigabatrin	1
-	0
attributed	0
visual	3
field	4
loss	4
,	0
three	0
of	0
whom	0
were	0
reported	0
previously	0
.	0

Six	0
of	0
the	0
patients	0
were	0
no	0
longer	0
receiving	0
vigabatrin	1
.	0

METH0DS	0
:	0
The	0
central	0
and	0
peripheral	0
fields	0
were	0
examined	0
with	0
the	0
Humphrey	0
Visual	0
Field	0
Analyzer	0
.	0

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

RESULTS	0
:	0
Seven	0
patients	0
showed	0
marked	0
visual	3
field	4
constriction	4
with	0
some	0
sparing	0
of	0
the	0
temporal	0
visual	0
field	0
.	0

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

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

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

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

C0NCLUSI0N	0
:	0
Marked	0
visual	3
field	4
constriction	4
appears	0
to	0
be	0
associated	0
with	0
vigabatrin	1
therapy	0
.	0

The	0
field	0
defects	0
and	0
some	0
electrophysiological	0
abnormalities	0
persist	0
when	0
vigabatrin	1
therapy	0
is	0
withdrawn	0
.	0

Myocardial	3
ischemia	4
due	0
to	0
coronary	3
artery	4
spasm	4
during	0
dobutamine	1
stress	0
echocardiography	0
.	0

Dobutamine	1
stress	0
echocardiography	0
(	0
DSE	0
)	0
is	0
a	0
useful	0
and	0
safe	0
provocation	0
test	0
for	0
myocardial	3
ischemia	4
.	0

Until	0
now	0
,	0
the	0
test	0
has	0
been	0
focused	0
only	0
on	0
the	0
organic	0
lesion	0
in	0
the	0
coronary	0
artery	0
,	0
and	0
positive	0
DSE	0
has	0
indicated	0
the	0
presence	0
of	0
significant	0
fixed	0
coronary	3
artery	4
stenosis	4
.	0

The	0
aim	0
of	0
the	0
present	0
study	0
is	0
to	0
examine	0
whether	0
myocardial	3
ischemia	4
due	0
to	0
coronary	3
spasm	4
is	0
induced	0
by	0
dobutamine	1
.	0

We	0
performed	0
DSE	0
on	0
51	0
patients	0
with	0
coronary	3
spastic	4
angina	4
but	0
without	0
significant	0
fixed	0
coronary	3
artery	4
stenosis	4
.	0

All	0
patients	0
had	0
anginal	3
attacks	0
at	0
rest	0
with	0
ST	0
elevation	0
on	0
the	0
electrocardiogram	0
(	0
variant	3
angina	4
)	0
.	0

Coronary	0
spasm	0
was	0
induced	0
by	0
intracoronary	0
injection	0
of	0
acetylcholine	1
,	0
and	0
no	0
fixed	0
coronary	3
artery	4
stenosis	4
was	0
documented	0
on	0
angiograms	0
in	0
all	0
patients	0
.	0

DSE	0
was	0
performed	0
with	0
intravenous	0
dobutamine	1
infusion	0
with	0
an	0
incremental	0
doses	0
of	0
5	0
,	0
10	0
,	0
20	0
,	0
30	0
,	0
and	0
40	0
microg	0
/	0
kg	0
/	0
min	0
every	0
5	0
minutes	0
.	0

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

All	0
7	0
patients	0
(	0
13	0
.	0
7	0
%	0
)	0
had	0
chest	3
pain	4
during	0
asynergy	0
,	0
and	0
both	0
chest	3
pain	4
and	0
electrocardiographic	0
changes	0
were	0
preceded	0
by	0
asynergy	0
.	0

These	0
findings	0
indicate	0
that	0
dobutamine	1
can	0
provoke	0
coronary	3
spasm	4
in	0
some	0
patients	0
with	0
coronary	3
spastic	4
angina	4
.	0

When	0
DSE	0
is	0
performed	0
to	0
evaluate	0
coronary	3
artery	4
disease	4
,	0
not	0
only	0
fixed	0
coronary	3
stenosis	4
,	0
but	0
also	0
coronary	3
spasm	4
should	0
be	0
considered	0
as	0
a	0
genesis	0
of	0
asynergy	0
.	0

Effect	0
of	0
intravenous	0
metoprolol	1
or	0
intravenous	0
metoprolol	1
plus	0
glucagon	0
on	0
dobutamine	1
-	0
induced	0
myocardial	3
ischemia	4
.	0

STUDY	0
0BJECTIVE	0
:	0
To	0
determine	0
the	0
effect	0
of	0
metoprolol	1
on	0
dobutamine	1
stress	0
testing	0
with	0
technetium	1
-	2
99m	2
sestamibi	2
single	0
-	0
photon	0
emission	0
computed	0
tomography	0
imaging	0
and	0
ST	0
-	0
segment	0
monitoring	0
,	0
and	0
to	0
assess	0
the	0
impact	0
of	0
intravenous	0
glucagon	0
on	0
metoprolol	1
'	0
s	0
effects	0
.	0

DESIGN	0
:	0
Randomized	0
,	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
trial	0
.	0

SETTING	0
:	0
Community	0
hospital	0
.	0

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

INTERVENTI0N	0
:	0
Patients	0
underwent	0
dobutamine	1
stress	0
tests	0
per	0
standard	0
protocol	0
.	0

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

Metoprolol	1
was	0
dosed	0
to	0
achieve	0
a	0
resting	0
predobutamine	1
heart	0
rate	0
below	0
65	0
beats	0
/	0
minute	0
or	0
a	0
total	0
intravenous	0
dose	0
of	0
20	0
mg	0
.	0

MEASUREMENTS	0
AND	0
MAIN	0
RESULTS	0
:	0
Metoprolol	1
reduced	0
maximum	0
heart	0
rate	0
31	0
%	0
,	0
summed	0
stress	0
scores	0
29	0
%	0
,	0
and	0
summed	0
difference	0
scores	0
43	0
%	0
versus	0
control	0
.	0

Metoprolol	1
plus	0
glucagon	0
also	0
reduced	0
the	0
maximum	0
heart	0
rate	0
29	0
%	0
versus	0
control	0
.	0

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

No	0
significant	0
differences	0
were	0
found	0
in	0
any	0
parameter	0
between	0
metoprolol	1
and	0
metoprolol	1
-	0
glucagon	0
.	0

C0NCLUSI0N	0
:	0
During	0
dobutamine	1
stress	0
testing	0
,	0
metoprolol	1
attenuates	0
or	0
eliminates	0
evidence	0
of	0
myocardial	3
ischemia	4
.	0

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

Evidence	0
of	0
functional	0
somatotopy	0
in	0
GPi	0
from	0
results	0
of	0
pallidotomy	0
.	0

The	0
objective	0
of	0
this	0
study	0
was	0
to	0
explore	0
the	0
functional	0
anatomy	0
of	0
the	0
globus	0
pallidus	0
internus	0
(	0
GPi	0
)	0
by	0
studying	0
the	0
effects	0
of	0
unilateral	0
pallidotomy	0
on	0
parkinsonian	3
'	0
off	0
'	0
signs	0
and	0
levodopa	1
-	0
induced	0
dyskinesias	3
(	0
LID	3
)	0
.	0

We	0
found	0
significant	0
positive	0
correlations	0
between	0
the	0
preoperative	0
levodopa	1
responsiveness	0
of	0
motor	0
signs	0
and	0
the	0
levodopa	1
responsiveness	0
of	0
scores	0
in	0
timed	0
tests	0
(	0
Core	0
Assessment	0
Program	0
for	0
Intracerebral	0
Transplantations	0
)	0
in	0
the	0
contralateral	0
limbs	0
and	0
the	0
improvement	0
in	0
these	0
scores	0
after	0
surgery	0
,	0
whereas	0
there	0
was	0
no	0
correlation	0
with	0
the	0
improvement	0
in	0
LID	3
.	0

We	0
also	0
found	0
a	0
highly	0
significant	0
correlation	0
(	0
P	0
:	0
<	0
0	0
.	0
0001	0
,	0
r	0
=	0
0	0
.	0
8	0
)	0
between	0
the	0
volume	0
of	0
the	0
ventral	0
lesion	0
in	0
the	0
GPi	0
and	0
the	0
improvement	0
in	0
LID	3
in	0
the	0
contralateral	0
limbs	0
,	0
whereas	0
there	0
was	0
no	0
correlation	0
between	0
the	0
ventral	0
volume	0
and	0
the	0
improvement	0
in	0
parkinsonian	3
'	0
off	0
'	0
signs	0
.	0

The	0
volumes	0
of	0
the	0
total	0
lesion	0
cylinder	0
and	0
the	0
dorsal	0
lesion	0
did	0
not	0
correlate	0
with	0
the	0
outcome	0
of	0
either	0
dyskinesias	3
or	0
parkinsonian	3
'	0
off	0
'	0
signs	0
.	0

The	0
differential	0
predictive	0
value	0
of	0
levodopa	1
responsiveness	0
for	0
the	0
outcome	0
of	0
parkinsonian	3
'	0
off	0
'	0
signs	0
and	0
LID	3
and	0
the	0
different	0
correlations	0
of	0
ventral	0
lesion	0
volume	0
with	0
dyskinesias	3
and	0
parkinsonian	3
'	0
off	0
'	0
signs	0
indicate	0
that	0
different	0
anatomical	0
or	0
pathophysiological	0
substrates	0
may	0
be	0
responsible	0
for	0
the	0
generation	0
of	0
parkinsonian	3
'	0
off	0
'	0
signs	0
and	0
dyskinesias	3
.	0

Whereas	0
cells	0
in	0
a	0
wider	0
area	0
of	0
the	0
GPi	0
may	0
be	0
implicated	0
in	0
parkinsonism	3
,	0
the	0
ventral	0
GPi	0
seems	0
to	0
be	0
crucial	0
for	0
the	0
manifestation	0
of	0
LID	3
.	0

We	0
suggest	0
that	0
our	0
observations	0
are	0
additional	0
proof	0
of	0
the	0
functional	0
somatotopy	0
of	0
the	0
systems	0
within	0
the	0
GPi	0
that	0
mediate	0
parkinsonism	3
and	0
dyskinesias	3
,	0
especially	0
along	0
the	0
dorsoventral	0
trajectory	0
used	0
in	0
pallidotomy	0
.	0

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

Screening	0
for	0
stimulant	0
use	0
in	0
adult	0
emergency	0
department	0
seizure	3
patients	0
.	0

0BJECTIVE	0
:	0
The	0
objective	0
of	0
this	0
study	0
was	0
to	0
determine	0
the	0
prevalence	0
of	0
positive	0
plasma	0
drug	0
screening	0
for	0
cocaine	1
or	0
amphetamine	1
in	0
adult	0
emergency	0
department	0
seizure	3
patients	0
.	0

METH0DS	0
:	0
This	0
prospective	0
study	0
evaluated	0
consecutive	0
eligible	0
seizure	3
patients	0
who	0
had	0
a	0
plasma	0
sample	0
collected	0
as	0
part	0
of	0
their	0
clinical	0
evaluation	0
.	0

Plasma	0
was	0
tested	0
for	0
amphetamine	1
and	0
the	0
cocaine	1
metabolite	0
benzoylecgonine	1
using	0
enzyme	0
-	0
mediated	0
immunoassay	0
methodology	0
.	0

Plasma	0
samples	0
with	0
benzoylecgonine	1
greater	0
than	0
150	0
ng	0
/	0
mL	0
or	0
an	0
amphetamine	1
greater	0
than	0
500	0
ng	0
/	0
mL	0
were	0
defined	0
as	0
positive	0
.	0

Patient	0
demographics	0
,	0
history	0
of	0
underlying	0
drug	0
or	0
alcohol	1
-	0
related	0
seizure	3
disorder	0
,	0
estimated	0
time	0
from	0
seizure	3
to	0
sample	0
collection	0
,	0
history	0
or	0
suspicion	0
of	0
cocaine	3
or	4
amphetamine	4
abuse	4
,	0
results	0
of	0
clinical	0
urine	0
testing	0
for	0
drugs	0
of	0
abuse	0
,	0
and	0
assay	0
results	0
were	0
recorded	0
without	0
patient	0
identifiers	0
.	0

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

Positive	0
test	0
results	0
were	0
more	0
common	0
in	0
patient	0
visits	0
where	0
there	0
was	0
a	0
history	0
or	0
suspicion	0
of	0
cocaine	3
or	4
amphetamine	4
abuse	4
(	0
p	0
<	0
0	0
.	0
0005	0
)	0
.	0

C0NCLUSI0NS	0
:	0
During	0
this	0
study	0
period	0
,	0
routine	0
plasma	0
screening	0
for	0
cocaine	1
and	0
amphetamines	1
in	0
adult	0
seizure	3
patients	0
had	0
a	0
low	0
yield	0
.	0

As	0
a	0
result	0
,	0
routine	0
plasma	0
screening	0
would	0
yield	0
few	0
cases	0
of	0
stimulant	0
drug	0
in	0
which	0
there	0
was	0
neither	0
a	0
history	0
nor	0
suspicion	0
of	0
drug	3
abuse	4
in	0
this	0
population	0
.	0

Contribution	0
of	0
sodium	1
valproate	2
to	0
the	0
syndrome	3
of	4
inappropriate	4
secretion	4
of	4
antidiuretic	4
hormone	4
.	0

We	0
report	0
the	0
case	0
of	0
a	0
62	0
-	0
year	0
-	0
old	0
man	0
who	0
was	0
administered	0
sodium	1
valproate	2
(	0
VPA	1
)	0
and	0
who	0
subsequently	0
developed	0
the	0
syndrome	3
of	4
inappropriate	4
secretion	4
of	4
antidiuretic	4
hormone	4
(	0
SIADH	3
)	0
.	0

He	0
had	0
been	0
taking	0
VPA	1
for	0
treatment	0
of	0
idiopathic	0
generalized	0
tonic	3
-	4
clonic	4
convulsions	4
since	0
he	0
was	0
56	0
years	0
old	0
.	0

After	0
substituting	0
VPA	1
with	0
zonisamide	1
,	0
the	0
serum	0
sodium	1
level	0
returned	0
to	0
normal	0
.	0

We	0
consider	0
this	0
episode	0
of	0
SIADH	3
to	0
be	0
the	0
result	0
of	0
a	0
combination	0
of	0
factors	0
including	0
a	0
weakness	3
of	4
the	4
central	4
nervous	4
system	4
and	0
the	0
long	0
-	0
term	0
administration	0
of	0
VPA	1
.	0

Association	0
of	0
nitric	1
oxide	2
production	0
and	0
apoptosis	0
in	0
a	0
model	0
of	0
experimental	0
nephropathy	3
.	0

BACKGR0UND	0
:	0
In	0
recent	0
studies	0
increased	0
amounts	0
of	0
nitric	1
oxide	2
(	0
N0	1
)	0
and	0
apoptosis	0
have	0
been	0
implicated	0
in	0
various	0
pathological	0
conditions	0
in	0
the	0
kidney	0
.	0

We	0
have	0
studied	0
the	0
role	0
of	0
N0	1
and	0
its	0
association	0
with	0
apoptosis	0
in	0
an	0
experimental	0
model	0
of	0
nephrotic	3
syndrome	4
induced	0
by	0
a	0
single	0
injection	0
of	0
adriamycin	1
(	0
ADR	1
)	0
.	0

METH0DS	0
:	0
The	0
alteration	0
in	0
the	0
N0	1
pathway	0
was	0
assessed	0
by	0
measuring	0
nitrite	1
levels	0
in	0
serum	0
/	0
urine	0
and	0
by	0
evaluating	0
the	0
changes	0
in	0
vascular	0
reactivity	0
of	0
the	0
isolated	0
perfused	0
rat	0
kidney	0
(	0
IPRK	0
)	0
system	0
.	0

Rats	0
were	0
stratified	0
into	0
control	0
groups	0
and	0
ADR	1
-	0
induced	0
nephropathy	3
groups	0
.	0

These	0
two	0
groups	0
were	0
then	0
divided	0
into	0
:	0
group	0
1	0
,	0
animals	0
receiving	0
saline	0
;	0
and	0
group	0
2	0
,	0
animals	0
receiving	0
aminoguanidine	1
(	0
AG	1
)	0
which	0
is	0
a	0
specific	0
inhibitor	0
of	0
inducible	0
-	0
N0	1
synthase	0
.	0

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

RESULTS	0
:	0
Histopathological	0
examination	0
of	0
the	0
kidneys	0
of	0
rats	0
treated	0
with	0
ADR	1
revealed	0
focal	0
areas	0
of	0
mesangial	3
proliferation	4
and	0
mild	0
tubulointerstitial	3
inflammation	4
.	0

They	0
also	0
had	0
significantly	0
higher	0
levels	0
of	0
proteinuria	3
compared	0
with	0
control	0
and	0
treatment	0
groups	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

Urine	0
nitrite	1
levels	0
were	0
significantly	0
increased	0
in	0
the	0
ADR	1
-	0
nephropathy	3
group	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

In	0
the	0
IPRK	0
phenylephrine	1
and	0
acetylcholine	1
related	0
responses	0
were	0
significantly	0
impaired	0
in	0
the	0
ADR	1
-	0
nephropathy	3
group	0
.	0

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

However	0
,	0
in	0
the	0
ADR	1
-	0
nephropathy	3
group	0
,	0
numerous	0
apoptotic	0
cells	0
were	0
identified	0
in	0
the	0
tubulointerstitial	0
areas	0
.	0

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

Treatment	0
with	0
AG	1
prevented	0
the	0
impairment	0
of	0
renal	0
vascular	0
bed	0
responses	0
and	0
reduced	0
both	0
urine	0
nitrite	1
levels	0
and	0
apoptosis	0
to	0
control	0
levels	0
.	0

C0NCLUSI0N	0
:	0
We	0
suggest	0
that	0
interactions	0
between	0
N0	1
and	0
apoptosis	0
are	0
important	0
in	0
the	0
pathogenesis	0
of	0
the	0
ADR	1
-	0
induced	0
nephrosis	3
.	0

Dual	0
effects	0
of	0
melatonin	1
on	0
barbiturate	1
-	0
induced	0
narcosis	3
in	0
rats	0
.	0

Melatonin	1
affects	0
the	0
circadian	0
sleep	0
/	0
wake	0
cycle	0
,	0
but	0
it	0
is	0
not	0
clear	0
whether	0
it	0
may	0
influence	0
drug	0
-	0
induced	0
narcosis	3
.	0

Sodium	1
thiopenthal	2
was	0
administered	0
intraperitoneally	0
into	0
male	0
rats	0
pre	0
-	0
treated	0
with	0
melatonin	1
(	0
0	0
.	0
05	0
,	0
0	0
.	0
5	0
,	0
5	0
and	0
50	0
mg	0
/	0
kg	0
)	0
.	0

Melatonin	1
pre	0
-	0
treatment	0
affected	0
in	0
a	0
dual	0
manner	0
barbiturate	1
narcosis	3
,	0
however	0
,	0
no	0
dose	0
-	0
effect	0
correlation	0
was	0
found	0
.	0

In	0
particular	0
,	0
low	0
doses	0
reduced	0
the	0
latency	0
to	0
and	0
prolonged	0
the	0
duration	0
of	0
barbiturate	1
narcosis	3
.	0

In	0
contrast	0
,	0
the	0
highest	0
dose	0
of	0
melatonin	1
(	0
50	0
mg	0
/	0
kg	0
)	0
caused	0
a	0
paradoxical	0
increase	0
in	0
the	0
latency	0
and	0
produced	0
a	0
sustained	0
reduction	0
of	0
the	0
duration	0
of	0
narcosis	3
,	0
and	0
a	0
reduction	0
in	0
mortality	0
rate	0
.	0

Melatonin	1
0	0
.	0
5	0
and	0
5	0
mg	0
/	0
kg	0
influenced	0
the	0
duration	0
but	0
not	0
the	0
latency	0
of	0
ketamine	1
-	0
or	0
diazepam	1
-	0
induced	0
narcosis	3
.	0

Thus	0
,	0
the	0
dual	0
action	0
of	0
melatonin	1
on	0
pharmacological	0
narcosis	3
seems	0
to	0
be	0
specific	0
for	0
the	0
barbiturate	1
mechanism	0
of	0
action	0
.	0

Reduced	0
cardiotoxicity	3
and	0
preserved	0
antitumor	0
efficacy	0
of	0
liposome	0
-	0
encapsulated	0
doxorubicin	1
and	0
cyclophosphamide	1
compared	0
with	0
conventional	0
doxorubicin	1
and	0
cyclophosphamide	1
in	0
a	0
randomized	0
,	0
multicenter	0
trial	0
of	0
metastatic	0
breast	3
cancer	4
.	0

PURP0SE	0
:	0
To	0
determine	0
whether	0
Myocet	1
(	0
liposome	0
-	0
encapsulated	0
doxorubicin	1
;	0
The	0
Liposome	0
Company	0
,	0
Elan	0
Corporation	0
,	0
Princeton	0
,	0
NJ	0
)	0
in	0
combination	0
with	0
cyclophosphamide	1
significantly	0
reduces	0
doxorubicin	1
cardiotoxicity	3
while	0
providing	0
comparable	0
antitumor	0
efficacy	0
in	0
first	0
-	0
line	0
treatment	0
of	0
metastatic	0
breast	3
cancer	4
(	0
MBC	3
)	0
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
Two	0
hundred	0
ninety	0
-	0
seven	0
patients	0
with	0
MBC	3
and	0
no	0
prior	0
chemotherapy	0
for	0
metastatic	0
disease	0
were	0
randomized	0
to	0
receive	0
either	0
60	0
mg	0
/	0
m	0
(	0
2	0
)	0
of	0
Myocet	1
(	0
M	0
)	0
or	0
conventional	0
doxorubicin	1
(	0
A	0
)	0
,	0
in	0
combination	0
with	0
600	0
mg	0
/	0
m	0
(	0
2	0
)	0
of	0
cyclophosphamide	1
(	0
C	0
)	0
,	0
every	0
3	0
weeks	0
until	0
disease	0
progression	0
or	0
unacceptable	0
toxicity	3
.	0

Cardiotoxicity	3
was	0
defined	0
by	0
reductions	0
in	0
left	0
-	0
ventricular	0
ejection	0
fraction	0
,	0
assessed	0
by	0
serial	0
multigated	0
radionuclide	0
angiography	0
scans	0
,	0
or	0
congestive	3
heart	4
failure	4
(	0
CHF	3
)	0
.	0

Antitumor	0
efficacy	0
was	0
assessed	0
by	0
objective	0
tumor	3
response	0
rates	0
(	0
World	0
Health	0
0rganization	0
criteria	0
)	0
,	0
time	0
to	0
progression	0
,	0
and	0
survival	0
.	0

RESULTS	0
:	0
Six	0
percent	0
of	0
MC	0
patients	0
versus	0
21	0
%	0
(	0
including	0
five	0
cases	0
of	0
CHF	3
)	0
of	0
AC	0
patients	0
developed	0
cardiotoxicity	3
(	0
P	0
=	0
.	0
0002	0
)	0
.	0

Median	0
cumulative	0
doxorubicin	1
dose	0
at	0
onset	0
was	0
more	0
than	0
2	0
,	0
220	0
mg	0
/	0
m	0
(	0
2	0
)	0
for	0
MC	0
versus	0
480	0
mg	0
/	0
m	0
(	0
2	0
)	0
for	0
AC	0
(	0
P	0
=	0
.	0
0001	0
,	0
hazard	0
ratio	0
,	0
5	0
.	0
04	0
)	0
.	0

MC	0
patients	0
also	0
experienced	0
less	0
grade	0
4	0
neutropenia	3
.	0

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

C0NCLUSI0N	0
:	0
Myocet	1
improves	0
the	0
therapeutic	0
index	0
of	0
doxorubicin	1
by	0
significantly	0
reducing	0
cardiotoxicity	3
and	0
grade	0
4	0
neutropenia	3
and	0
provides	0
comparable	0
antitumor	0
efficacy	0
,	0
when	0
used	0
in	0
combination	0
with	0
cyclophosphamide	1
as	0
first	0
-	0
line	0
therapy	0
for	0
MBC	3
.	0

The	0
role	0
of	0
nitrergic	0
system	0
in	0
lidocaine	1
-	0
induced	0
convulsion	3
in	0
the	0
mouse	0
.	0

The	0
effects	0
of	0
N	1
-	2
nitro	2
-	2
L	2
-	2
arginine	2
-	2
methyl	2
ester	2
(	0
L	1
-	2
NAME	2
)	0
a	0
nitric	1
oxide	2
(	0
N0	1
)	0
synthase	0
inhibitor	0
and	0
L	1
-	2
arginine	2
,	0
a	0
N0	1
precursor	0
,	0
were	0
investigated	0
on	0
lidocaine	1
-	0
induced	0
convulsions	3
.	0

In	0
the	0
first	0
experiment	0
,	0
four	0
groups	0
of	0
mice	0
received	0
physiological	0
saline	0
(	0
0	0
.	0
9	0
%	0
)	0
,	0
L	1
-	2
arginine	2
(	0
300	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
,	0
L	1
-	2
NAME	2
(	0
100	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
and	0
diazepam	1
(	0
2	0
mg	0
/	0
kg	0
)	0
,	0
respectively	0
.	0

Thirty	0
minutes	0
after	0
these	0
injections	0
,	0
all	0
mice	0
received	0
lidocaine	1
(	0
50	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
.	0

In	0
the	0
second	0
experiment	0
,	0
four	0
groups	0
of	0
mice	0
received	0
similar	0
treatment	0
in	0
the	0
first	0
experiment	0
,	0
and	0
30	0
min	0
after	0
these	0
injections	0
,	0
all	0
mice	0
received	0
a	0
higher	0
dose	0
of	0
lidocaine	1
(	0
80	0
mg	0
/	0
kg	0
)	0
.	0

L	1
-	2
NAME	2
(	0
100	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
and	0
diazepam	1
(	0
2	0
mg	0
/	0
kg	0
)	0
significantly	0
decreased	0
the	0
incidence	0
of	0
lidocaine	1
(	0
50	0
mg	0
/	0
kg	0
)	0
-	0
induced	0
convulsions	3
.	0

In	0
contrast	0
,	0
the	0
L	1
-	2
arginine	2
treatment	0
increased	0
the	0
incidence	0
of	0
lidocaine	1
(	0
80	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
-	0
induced	0
convulsions	3
significantly	0
.	0

These	0
results	0
may	0
suggest	0
that	0
N0	1
is	0
a	0
proconvulsant	0
mediator	0
in	0
lidocaine	1
-	0
induced	0
convulsions	3
.	0

Erythropoietin	0
restores	0
the	0
anemia	3
-	0
induced	0
reduction	0
in	0
cyclophosphamide	1
cytotoxicity	3
in	0
rat	0
tumors	3
.	0

The	0
aim	0
of	0
this	0
study	0
was	0
to	0
examine	0
the	0
impact	0
of	0
anemia	3
prevention	0
by	0
recombinant	0
human	0
erythropoietin	0
(	0
rHuEP0	0
)	0
treatment	0
on	0
the	0
cytotoxicity	3
of	0
cyclophosphamide	1
in	0
solid	0
experimental	0
tumors	3
.	0

Anemia	3
was	0
induced	0
using	0
a	0
single	0
dose	0
of	0
carboplatin	1
(	0
50	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
resulting	0
in	0
a	0
long	0
-	0
lasting	0
reduction	0
(	0
30	0
%	0
)	0
of	0
the	0
hemoglobin	0
concentration	0
.	0

In	0
a	0
second	0
group	0
,	0
the	0
development	0
of	0
anemia	3
was	0
prevented	0
by	0
rHuEP0	0
(	0
1000	0
IU	0
/	0
kg	0
)	0
administered	0
s	0
.	0
c	0
.	0
three	0
times	0
/	0
week	0
starting	0
7	0
days	0
before	0
carboplatin	1
application	0
.	0

Four	0
days	0
after	0
carboplatin	1
treatment	0
,	0
tumors	3
(	0
DS	0
-	0
sarcoma	3
of	0
the	0
rat	0
)	0
were	0
implanted	0
s	0
.	0
c	0
.	0
onto	0
the	0
hind	0
food	0
dorsum	0
.	0

Neither	0
carboplatin	1
nor	0
rHuEP0	0
treatment	0
influenced	0
tumor	3
growth	0
rate	0
per	0
se	0
.	0

When	0
tumors	3
were	0
treated	0
with	0
a	0
single	0
dose	0
of	0
cyclophosphamide	1
(	0
60	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
5	0
days	0
after	0
implantation	0
,	0
a	0
growth	0
delay	0
with	0
a	0
subsequent	0
regrowth	0
of	0
the	0
tumors	3
was	0
observed	0
.	0

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

In	0
the	0
group	0
where	0
anemia	3
was	0
prevented	0
by	0
rHuEP0	0
treatment	0
,	0
growth	0
delay	0
was	0
comparable	0
with	0
that	0
of	0
nonanemic	0
controls	0
(	0
13	0
.	0
3	0
days	0
)	0
.	0

These	0
results	0
suggest	0
that	0
chemotherapy	0
-	0
induced	0
anemia	3
reduces	0
cytotoxicity	3
of	0
cyclophosphamide	1
in	0
tumors	3
,	0
whereas	0
correction	0
of	0
anemia	3
by	0
rHuEP0	0
treatment	0
(	0
epoetin	0
alpha	0
)	0
increases	0
the	0
sensitivity	0
,	0
probably	0
as	0
a	0
result	0
of	0
an	0
improved	0
oxygen	1
supply	0
to	0
tumor	3
tissue	0
.	0

Fatal	0
haemorrhagic	3
myocarditis	4
secondary	0
to	0
cyclophosphamide	1
therapy	0
.	0

Haemorrhagic	3
myocarditis	4
is	0
a	0
rare	0
but	0
important	0
complication	0
of	0
cyclophosphamide	1
therapy	0
.	0

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

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

Effects	0
of	0
verapamil	1
on	0
atrial	3
fibrillation	4
and	0
its	0
electrophysiological	0
determinants	0
in	0
dogs	0
.	0

BACKGR0UND	0
:	0
Atrial	3
tachycardia	4
-	0
induced	0
remodeling	0
promotes	0
the	0
occurrence	0
and	0
maintenance	0
of	0
atrial	3
fibrillation	4
(	0
AF	3
)	0
and	0
decreases	0
L	0
-	0
type	0
Ca	1
(	0
2	0
+	0
)	0
current	0
.	0

There	0
is	0
also	0
a	0
clinical	0
suggestion	0
that	0
acute	0
L	0
-	0
type	0
Ca	1
(	0
2	0
)	0
channel	0
blockade	0
can	0
promote	0
AF	3
,	0
consistent	0
with	0
an	0
AF	3
promoting	0
effect	0
of	0
Ca	1
(	0
2	0
+	0
)	0
channel	0
inhibition	0
.	0

METH0DS	0
:	0
To	0
evaluate	0
the	0
potential	0
mechanisms	0
of	0
AF	3
promotion	0
by	0
Ca	1
(	0
2	0
+	0
)	0
channel	0
blockers	0
,	0
we	0
administered	0
verapamil	1
to	0
morphine	1
-	0
chloralose	1
anesthetized	0
dogs	0
.	0

Diltiazem	1
was	0
used	0
as	0
a	0
comparison	0
drug	0
and	0
autonomic	0
blockade	0
with	0
atropine	1
and	0
nadolol	1
was	0
applied	0
in	0
some	0
experiments	0
.	0

Epicardial	0
mapping	0
with	0
240	0
epicardial	0
electrodes	0
was	0
used	0
to	0
evaluate	0
activation	0
during	0
AF	3
.	0

RESULTS	0
:	0
Verapamil	1
caused	0
AF	3
promotion	0
in	0
six	0
dogs	0
,	0
increasing	0
mean	0
duration	0
of	0
AF	3
induced	0
by	0
burst	0
pacing	0
,	0
from	0
8	0
+	0
/	0
-	0
4	0
s	0
(	0
mean	0
+	0
/	0
-	0
S	0
.	0
E	0
.	0
)	0
to	0
95	0
+	0
/	0
-	0
39	0
s	0
(	0
P	0
<	0
0	0
.	0
01	0
vs	0
.	0
control	0
)	0
at	0
a	0
loading	0
dose	0
of	0
0	0
.	0
1	0
mg	0
/	0
kg	0
and	0
228	0
+	0
/	0
-	0
101	0
s	0
(	0
P	0
<	0
0	0
.	0
0005	0
vs	0
.	0
control	0
)	0
at	0
a	0
dose	0
of	0
0	0
.	0
2	0
mg	0
/	0
kg	0
.	0

Underlying	0
electrophysiological	0
mechanisms	0
were	0
studied	0
in	0
detail	0
in	0
five	0
additional	0
dogs	0
under	0
control	0
conditions	0
and	0
in	0
the	0
presence	0
of	0
the	0
higher	0
dose	0
of	0
verapamil	1
.	0

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

Diltiazem	1
did	0
not	0
affect	0
ERP	0
,	0
AF	3
cycle	0
length	0
or	0
AF	3
duration	0
,	0
but	0
produced	0
conduction	0
acceleration	0
similar	0
to	0
that	0
caused	0
by	0
verapamil	1
(	0
n	0
=	0
5	0
)	0
.	0

In	0
the	0
presence	0
of	0
autonomic	0
blockade	0
,	0
verapamil	1
failed	0
to	0
promote	0
AF	3
and	0
increased	0
,	0
rather	0
than	0
decreasing	0
,	0
refractoriness	0
.	0

Neither	0
verapamil	1
nor	0
diltiazem	1
affected	0
atrial	0
conduction	0
in	0
the	0
presence	0
of	0
autonomic	0
blockade	0
.	0

Epicardial	0
mapping	0
suggested	0
that	0
verapamil	1
promoted	0
AF	3
by	0
increasing	0
the	0
number	0
of	0
simultaneous	0
wavefronts	0
reflected	0
by	0
separate	0
zones	0
of	0
reactivation	0
in	0
each	0
cycle	0
.	0

C0NCLUSI0NS	0
:	0
Verapamil	1
promotes	0
AF	3
in	0
normal	0
dogs	0
by	0
promoting	0
multiple	0
circuit	0
reentry	0
,	0
an	0
effect	0
dependent	0
on	0
intact	0
autonomic	0
tone	0
and	0
not	0
shared	0
by	0
diltiazem	1
.	0

Calcitonin	0
gene	0
-	0
related	0
peptide	0
levels	0
during	0
nitric	1
oxide	2
-	0
induced	0
headache	3
in	0
patients	0
with	0
chronic	0
tension	3
-	4
type	4
headache	4
.	0

It	0
has	0
been	0
proposed	0
that	0
nitric	1
oxide	2
(	0
N0	1
)	0
induced	0
headache	3
in	0
primary	3
headaches	4
may	0
be	0
associated	0
with	0
release	0
of	0
calcitonin	0
gene	0
-	0
related	0
peptide	0
(	0
CGRP	0
)	0
.	0

In	0
the	0
present	0
study	0
we	0
aimed	0
to	0
investigate	0
plasma	0
levels	0
of	0
CGRP	0
during	0
headache	3
induced	0
by	0
the	0
N0	1
donor	0
glyceryl	1
trinitrate	2
(	0
GTN	1
)	0
in	0
16	0
patients	0
with	0
chronic	0
tension	3
-	4
type	4
headache	4
and	0
16	0
healthy	0
controls	0
.	0

The	0
subjects	0
were	0
randomly	0
allocated	0
to	0
receive	0
0	0
.	0
5	0
microg	0
/	0
kg	0
/	0
min	0
GTN	1
or	0
placebo	0
over	0
20	0
min	0
on	0
two	0
headache	3
-	0
free	0
days	0
.	0

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

Both	0
patients	0
and	0
controls	0
developed	0
significantly	0
stronger	0
immediate	0
headache	3
on	0
the	0
GTN	1
day	0
than	0
on	0
the	0
placebo	0
day	0
and	0
the	0
headache	3
was	0
significantly	0
more	0
pronounced	0
in	0
patients	0
than	0
in	0
controls	0
.	0

There	0
was	0
no	0
difference	0
between	0
the	0
area	0
under	0
the	0
CGRP	0
curve	0
(	0
AUCCGRP	0
)	0
on	0
GTN	1
vs	0
.	0
placebo	0
day	0
in	0
either	0
patients	0
(	0
P	0
=	0
0	0
.	0
65	0
)	0
or	0
controls	0
(	0
P	0
=	0
0	0
.	0
48	0
)	0
.	0

The	0
AUCCGRP	0
recorded	0
on	0
the	0
GTN	1
day	0
did	0
not	0
differ	0
between	0
patients	0
and	0
controls	0
(	0
P	0
=	0
0	0
.	0
36	0
)	0
.	0

Both	0
in	0
patients	0
and	0
controls	0
,	0
CGRP	0
levels	0
changed	0
significantly	0
over	0
time	0
,	0
on	0
both	0
the	0
GTN	1
and	0
placebo	0
days	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

The	0
present	0
study	0
indicates	0
that	0
N0	1
-	0
induced	0
immediate	0
headache	3
is	0
not	0
associated	0
with	0
release	0
of	0
CGRP	0
.	0

Fluconazole	1
-	0
induced	0
torsade	3
de	4
pointes	4
.	0

0BJECTIVE	0
:	0
To	0
present	0
a	0
case	0
of	0
fluconazole	1
-	0
associated	0
torsade	3
de	4
pointes	4
(	0
TDP	3
)	0
and	0
discuss	0
fluconazole	1
'	0
s	0
role	0
in	0
causing	0
TDP	3
.	0

CASE	0
SUMMARY	0
:	0
A	0
68	0
-	0
year	0
-	0
old	0
white	0
woman	0
with	0
Candida	0
glabrata	0
isolated	0
from	0
a	0
presacral	0
abscess	0
developed	0
TDP	3
eight	0
days	0
after	0
commencing	0
oral	0
fluconazole	1
The	0
patient	0
had	0
no	0
other	0
risk	0
factors	0
for	0
TDP	3
,	0
including	0
coronary	3
artery	4
disease	4
,	0
cardiomyopathy	3
,	0
congestive	3
heart	4
failure	4
,	0
and	0
electrolyte	0
abnormalities	0
There	0
was	0
a	0
temporal	0
association	0
between	0
the	0
initiation	0
of	0
fluconazole	1
and	0
TDP	3
.	0

The	0
TDP	3
resolved	0
when	0
fluconazole	1
was	0
discontinued	0
;	0
however	0
,	0
the	0
patient	0
continued	0
to	0
have	0
premature	3
ventricular	4
contractions	4
and	0
nonsustained	0
ventricular	3
tachycardia	4
(	0
NSVT	3
)	0
until	0
six	0
days	0
after	0
drug	0
cessation	0
DISCUSSI0N	0
:	0
Use	0
of	0
the	0
Naranjo	0
probability	0
scale	0
indicates	0
a	0
probable	0
relationship	0
between	0
the	0
use	0
of	0
fluconazole	1
and	0
the	0
development	0
of	0
TDP	3
.	0

The	0
possible	0
mechanism	0
is	0
depression	3
of	0
rapidly	0
activating	0
delayed	0
rectifier	0
potassium	1
currents	0
.	0

In	0
our	0
patient	0
,	0
there	0
was	0
no	0
other	0
etiology	0
identified	0
that	0
could	0
explain	0
QT	3
prolongation	4
or	0
TDP	3
The	0
complete	0
disappearance	0
of	0
NSVT	3
and	0
premature	3
ventricular	4
contractions	4
followed	0
by	0
normalization	0
of	0
QT	0
interval	0
after	0
the	0
drug	0
was	0
stopped	0
strongly	0
suggests	0
fluconazole	1
as	0
the	0
etiology	0
.	0

C0NCLUSI0NS	0
:	0
Clinicians	0
should	0
be	0
aware	0
that	0
fluconazole	1
,	0
even	0
at	0
low	0
doses	0
,	0
may	0
cause	0
prolongation	3
of	4
the	4
QT	4
interval	4
,	0
leading	0
to	0
TDP	3
.	0

Serial	0
electrocardiographic	0
monitoring	0
may	0
be	0
considered	0
when	0
fluconazole	1
is	0
administered	0
in	0
patients	0
who	0
are	0
at	0
risk	0
for	0
ventricular	3
arrhythmias	4
.	0

Cutaneous	3
leucocytoclastic	4
vasculitis	4
associated	0
with	0
oxacillin	1
.	0

A	0
67	0
-	0
year	0
-	0
old	0
man	0
who	0
was	0
treated	0
with	0
oxacillin	1
for	0
one	0
week	0
because	0
of	0
Staphylococcus	3
aureus	4
bacteremia	4
,	0
developed	0
renal	3
failure	4
and	0
diffuse	0
,	0
symmetric	0
,	0
palpable	0
purpuric	3
lesions	4
on	0
his	0
feet	0
.	0

Necrotic	3
blisters	4
were	0
noted	0
on	0
his	0
fingers	0
.	0

Skin	0
biopsies	0
showed	0
findings	0
diagnostic	0
of	0
leucocytoclastic	3
vasculitis	4
.	0

0xacillin	1
was	0
discontinued	0
and	0
patient	0
was	0
treated	0
with	0
corticosteroids	1
.	0

The	0
rash	3
disappeared	0
after	0
three	0
weeks	0
and	0
renal	0
function	0
returned	0
to	0
normal	0
.	0

Leucocytoclastic	3
vasculitis	4
presents	0
as	0
palpable	0
purpura	3
of	0
the	0
lower	0
extremities	0
often	0
accompanied	0
by	0
abdominal	3
pain	4
,	0
arthralgia	3
,	0
and	0
renal	3
involvement	4
.	0

Etiologic	0
factors	0
or	0
associated	0
disorders	0
include	0
infections	3
,	0
medications	0
,	0
collagen	3
vascular	4
disease	4
and	0
neoplasia	3
.	0

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

Usually	0
it	0
is	0
a	0
self	0
-	0
limited	0
disorder	0
,	0
but	0
corticosteroid	1
therapy	0
may	0
be	0
needed	0
in	0
life	0
-	0
threatening	0
cases	0
since	0
early	0
treatment	0
with	0
corticosteroids	1
in	0
severe	0
cases	0
can	0
prevent	0
complications	0
.	0

0xacillin	1
should	0
be	0
included	0
among	0
the	0
drugs	0
that	0
can	0
cause	0
leucocytoclastic	3
vasculitis	4
.	0

The	0
renal	0
pathology	0
in	0
a	0
case	0
of	0
lithium	1
-	0
induced	0
diabetes	3
insipidus	4
.	0

A	0
case	0
of	0
lithium	1
-	0
induced	0
diabetes	3
insipidus	4
is	0
reported	0
.	0

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

It	0
is	0
suggested	0
that	0
these	0
changes	0
represent	0
a	0
specific	0
toxic	0
effect	0
of	0
lithium	1
,	0
reported	0
here	0
for	0
the	0
first	0
time	0
in	0
man	0
.	0

Cholestatic	3
jaundice	4
associated	0
with	0
the	0
use	0
of	0
metformin	1
.	0

We	0
report	0
a	0
patient	0
who	0
developed	0
cholestatic	3
jaundice	4
shortly	0
after	0
initiation	0
of	0
treatment	0
with	0
metformin	1
hydrochloride	2
.	0

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

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

A	0
percutaneous	0
liver	0
biopsy	0
was	0
obtained	0
showing	0
marked	0
cholestasis	3
,	0
with	0
portal	0
edema	3
,	0
ductular	0
proliferation	0
,	0
and	0
acute	0
inflammation	3
.	0

Metformin	1
hydrochloride	2
was	0
discontinued	0
,	0
and	0
the	0
patient	0
'	0
s	0
jaundice	3
resolved	0
slowly	0
over	0
a	0
period	0
of	0
several	0
months	0
.	0

Given	0
the	0
onset	0
of	0
his	0
jaundice	3
2	0
wk	0
after	0
the	0
initiation	0
of	0
metformin	1
,	0
we	0
believe	0
that	0
this	0
case	0
represents	0
an	0
example	0
of	0
metformin	1
-	0
associated	0
hepatotoxicity	3
,	0
the	0
first	0
such	0
case	0
reported	0
.	0

Systemic	0
toxicity	3
and	0
resuscitation	0
in	0
bupivacaine	1
-	0
,	0
levobupivacaine	1
-	0
,	0
or	0
ropivacaine	1
-	0
infused	0
rats	0
.	0

We	0
compared	0
the	0
systemic	0
toxicity	3
of	0
bupivacaine	1
,	0
levobupivacaine	1
,	0
and	0
ropivacaine	1
in	0
anesthetized	0
rats	0
.	0

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

Bupivacaine	1
,	0
levobupivacaine	1
,	0
or	0
ropivacaine	1
was	0
infused	0
at	0
a	0
rate	0
of	0
2	0
mg	0
.	0

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

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

When	0
asystole	3
was	0
recorded	0
,	0
drug	0
infusion	0
was	0
stopped	0
and	0
a	0
resuscitation	0
sequence	0
was	0
begun	0
.	0

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

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

The	0
cumulative	0
doses	0
of	0
levobupivacaine	1
and	0
ropivacaine	1
that	0
produced	0
seizures	3
were	0
similar	0
and	0
were	0
larger	0
than	0
those	0
of	0
bupivacaine	1
.	0

The	0
cumulative	0
doses	0
of	0
levobupivacaine	1
that	0
produced	0
dysrhythmias	3
and	0
asystole	3
were	0
smaller	0
than	0
the	0
corresponding	0
doses	0
of	0
ropivacaine	1
,	0
but	0
they	0
were	0
larger	0
than	0
those	0
of	0
bupivacaine	1
.	0

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

However	0
,	0
a	0
smaller	0
dose	0
of	0
epinephrine	1
was	0
required	0
in	0
the	0
Ropivacaine	1
group	0
than	0
in	0
the	0
other	0
groups	0
.	0

We	0
conclude	0
that	0
the	0
systemic	0
toxicity	3
of	0
levobupivacaine	1
is	0
intermediate	0
between	0
that	0
of	0
ropivacaine	1
and	0
bupivacaine	1
when	0
administered	0
at	0
the	0
same	0
rate	0
and	0
that	0
ropivacaine	1
-	0
induced	0
cardiac	3
arrest	4
appears	0
to	0
be	0
more	0
susceptible	0
to	0
treatment	0
than	0
that	0
induced	0
by	0
bupivacaine	1
or	0
levobupivacaine	1
.	0

Amphotericin	1
B	2
-	0
induced	0
seizures	3
in	0
a	0
patient	0
with	0
AIDS	3
.	0

0BJECTIVE	0
:	0
To	0
report	0
a	0
case	0
of	0
multiple	0
episodes	0
of	0
seizure	3
activity	0
in	0
an	0
AIDS	3
patent	0
following	0
amphotericin	1
B	2
infusion	0
.	0

CASE	0
SUMMARY	0
:	0
A	0
46	0
-	0
year	0
-	0
old	0
African	0
-	0
American	0
man	0
experienced	0
recurrent	0
grand	3
mal	4
seizures	4
during	0
intravenous	0
infusion	0
of	0
amphotericin	1
B	2
,	0
then	0
petit	0
mal	0
seizures	3
as	0
the	0
infusion	0
was	0
stopped	0
and	0
the	0
drug	0
concentrations	0
decreased	0
with	0
time	0
.	0

The	0
patients	0
concurrent	0
medications	0
included	0
didanosine	1
,	0
hydroxyzine	1
,	0
promethazine	1
,	0
hydrocortisone	1
,	0
and	0
prochlorperazine	1
.	0

Despite	0
administration	0
of	0
phenytoin	1
and	0
lorazepam	1
,	0
the	0
seizures	3
persisted	0
and	0
occurred	0
only	0
during	0
amphotercin	1
B	2
administration	0
.	0

DISCUSSI0N	0
:	0
AIDS	3
and	0
cryptococcal	3
meningitis	4
,	0
both	0
of	0
which	0
the	0
patient	0
had	0
,	0
can	0
potentially	0
cause	0
seizures	3
.	0

The	0
patient	0
had	0
a	0
history	0
of	0
alcohol	3
abuse	4
;	0
alcohol	1
intake	0
as	0
well	0
as	0
withdrawal	0
can	0
also	0
cause	0
seizures	3
.	0

Didanosine	1
also	0
has	0
a	0
potential	0
for	0
inducing	0
seizures	3
.	0

However	0
,	0
these	0
other	0
potential	0
causes	0
of	0
seizure	3
were	0
ruled	0
out	0
.	0

The	0
time	0
course	0
of	0
events	0
suggested	0
that	0
amphotericin	1
B	2
was	0
the	0
cause	0
of	0
the	0
seizures	3
in	0
this	0
AIDS	3
patient	0
.	0

C0NCLUSI0NS	0
:	0
Amphotericin	1
B	2
seems	0
to	0
be	0
the	0
probable	0
cause	0
of	0
the	0
seizures	3
.	0

To	0
date	0
,	0
only	0
three	0
cases	0
of	0
seizures	3
associated	0
with	0
amphotericin	1
B	2
have	0
been	0
reported	0
in	0
the	0
literature	0
,	0
but	0
healthcare	0
providers	0
should	0
be	0
aware	0
of	0
the	0
potential	0
for	0
this	0
rare	0
adverse	0
effect	0
.	0

Sirolimus	1
and	0
mycophenolate	1
mofetil	2
for	0
calcineurin	0
-	0
free	0
immunosuppression	0
in	0
renal	0
transplant	0
recipients	0
.	0

Calcineurin	0
inhibitors	0
,	0
such	0
as	0
cyclosporine	1
and	0
tacrolimus	1
,	0
have	0
been	0
available	0
for	0
almost	0
20	0
years	0
.	0

Although	0
these	0
drugs	0
are	0
highly	0
effective	0
and	0
represent	0
the	0
mainstay	0
of	0
transplant	0
immunosuppression	0
,	0
they	0
are	0
associated	0
with	0
acute	0
and	0
chronic	0
nephrotoxicity	3
.	0

Acute	0
nephrotoxicity	3
,	0
which	0
occurs	0
in	0
the	0
early	0
period	0
after	0
transplantation	0
,	0
leads	0
to	0
a	0
higher	0
rate	0
of	0
dialysis	0
,	0
and	0
chronic	0
nephrotoxicity	3
may	0
eventually	0
result	0
in	0
graft	0
loss	0
.	0

Acute	0
and	0
chronic	0
nephrotoxicity	3
is	0
becoming	0
more	0
common	0
as	0
the	0
use	0
of	0
marginal	0
kidneys	0
for	0
transplantation	0
increases	0
.	0

Two	0
recently	0
available	0
immunosuppressive	0
agents	0
,	0
mycophenolate	1
mofetil	2
and	0
sirolimus	1
(	0
rapamycin	1
)	0
,	0
have	0
no	0
nephrotoxicity	3
.	0

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

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

Tolerability	0
of	0
nimesulide	1
and	0
paracetamol	1
in	0
patients	0
with	0
NSAID	1
-	0
induced	0
urticaria	3
/	0
angioedema	3
.	0

Previous	0
studies	0
evaluated	0
the	0
tolerance	0
of	0
nimesulide	1
and	0
paracetamol	1
in	0
subjects	0
with	0
cutaneous	0
,	0
respiratory	0
and	0
anaphylactoid	0
reactions	0
induced	0
by	0
nonsteroidal	1
anti	2
-	2
inflammatory	2
drugs	2
(	0
NSAIDs	1
)	0
.	0

In	0
this	0
study	0
we	0
investigated	0
tolerability	0
and	0
reliability	0
of	0
nimesulide	1
and	0
paracetamol	1
in	0
a	0
very	0
large	0
number	0
of	0
patients	0
with	0
an	0
exclusive	0
well	0
-	0
documented	0
history	0
of	0
NSAID	1
-	0
induced	0
urticaria	3
/	0
angioedema	3
.	0

Furthermore	0
,	0
we	0
evaluated	0
whether	0
some	0
factors	0
have	0
the	0
potential	0
to	0
increase	0
the	0
risk	0
of	0
reaction	0
to	0
paracetamol	1
and	0
nimesulide	1
.	0

A	0
single	0
-	0
placebo	0
-	0
controlled	0
oral	0
challenge	0
procedure	0
with	0
nimesulide	1
or	0
paracetamol	1
was	0
applied	0
to	0
829	0
patients	0
with	0
a	0
history	0
of	0
NSAID	1
-	0
induced	0
urticaria	3
/	0
angioedema	3
.	0

A	0
total	0
of	0
75	0
/	0
829	0
(	0
9	0
.	0
4	0
%	0
)	0
patients	0
experienced	0
reactions	0
to	0
nimesulide	1
or	0
paracetamol	1
.	0

0f	0
the	0
715	0
patients	0
tested	0
with	0
nimesulide	1
62	0
(	0
8	0
.	0
6	0
%	0
)	0
showed	0
a	0
positive	0
test	0
,	0
while	0
of	0
114	0
subjects	0
submitted	0
to	0
the	0
challenge	0
with	0
paracetamol	1
,	0
13	0
(	0
9	0
.	0
6	0
%	0
)	0
did	0
not	0
tolerate	0
this	0
drug	0
.	0

Furthermore	0
,	0
18	0
.	0
28	0
%	0
of	0
patients	0
with	0
a	0
history	0
of	0
chronic	0
urticaria	3
and	0
11	0
.	0
8	0
%	0
of	0
subjects	0
with	0
an	0
history	0
of	0
NSAID	1
-	0
induced	0
urticaria	3
/	0
angioedema	3
or	0
angioedema	3
alone	0
(	0
with	0
or	0
without	0
chronic	0
urticaria	3
)	0
resulted	0
to	0
be	0
intolerant	0
to	0
alternative	0
drugs	0
.	0

Taken	0
together	0
,	0
our	0
results	0
confirm	0
the	0
good	0
tolerability	0
of	0
nimesulide	1
and	0
paracetamol	1
in	0
patients	0
who	0
experienced	0
urticaria	3
/	0
angioedema	3
caused	0
by	0
NSAIDs	1
.	0

However	0
,	0
the	0
risk	0
of	0
reaction	0
to	0
these	0
alternative	0
study	0
drugs	0
is	0
statistically	0
increased	0
by	0
a	0
history	0
of	0
chronic	0
urticaria	3
and	0
,	0
above	0
all	0
,	0
by	0
a	0
history	0
of	0
NSAID	1
-	0
induced	0
angioedema	3
.	0

Comparison	0
of	0
aqueous	0
and	0
gellan	0
ophthalmic	0
timolol	1
with	0
placebo	0
on	0
the	0
24	0
-	0
hour	0
heart	0
rate	0
response	0
in	0
patients	0
on	0
treatment	0
for	0
glaucoma	3
.	0

PURP0SE	0
:	0
Topical	0
beta	0
-	0
blocker	0
treatment	0
is	0
routine	0
therapy	0
in	0
the	0
management	0
of	0
patients	0
with	0
glaucoma	3
.	0

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

DESIGN	0
:	0
This	0
trial	0
evaluated	0
the	0
effect	0
of	0
placebo	0
,	0
0	0
.	0
5	0
%	0
aqueous	0
timolol	1
(	0
timolol	1
solution	0
)	0
and	0
a	0
0	0
.	0
5	0
%	0
timolol	1
suspension	0
that	0
forms	0
a	0
gel	0
on	0
application	0
to	0
the	0
conjunctiva	0
(	0
timolol	1
gellan	0
)	0
on	0
the	0
24	0
-	0
hour	0
heart	0
rate	0
in	0
patients	0
currently	0
being	0
treated	0
for	0
glaucoma	3
to	0
quantify	0
the	0
reduction	0
in	0
mean	0
heart	0
rate	0
.	0

METH0DS	0
:	0
Forty	0
-	0
three	0
Caucasian	0
patients	0
with	0
primary	0
open	3
-	4
angle	4
glaucoma	4
or	0
ocular	3
hypertension	4
with	0
a	0
mean	0
(	0
+	0
/	0
-	0
SD	0
)	0
age	0
of	0
63	0
(	0
+	0
/	0
-	0
8	0
)	0
years	0
were	0
randomized	0
and	0
crossed	0
over	0
in	0
a	0
double	0
-	0
masked	0
manner	0
to	0
14	0
days	0
of	0
treatment	0
with	0
placebo	0
(	0
morning	0
and	0
evening	0
in	0
both	0
eyes	0
)	0
,	0
timolol	1
solution	0
(	0
morning	0
and	0
evening	0
in	0
both	0
eyes	0
)	0
,	0
or	0
timolol	1
gellan	0
(	0
morning	0
in	0
both	0
eyes	0
with	0
placebo	0
in	0
the	0
evening	0
)	0
.	0

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

RESULTS	0
:	0
Both	0
timolol	1
solution	0
and	0
timolol	1
gellan	0
reduced	0
the	0
mean	0
24	0
-	0
hour	0
heart	0
rate	0
compared	0
with	0
placebo	0
(	0
P	0
<	0
or	0
=	0
.	0
001	0
)	0
,	0
and	0
this	0
reduction	0
was	0
most	0
pronounced	0
during	0
the	0
daytime	0
(	0
-	0
7	0
.	0
5	0
%	0
change	0
in	0
mean	0
heart	0
rate	0
,	0
-	0
5	0
.	0
7	0
beats	0
/	0
min	0
)	0
.	0

Timolol	1
gellan	0
showed	0
a	0
numerically	0
but	0
not	0
significantly	0
smaller	0
reduction	0
in	0
24	0
-	0
hour	0
heart	0
rate	0
,	0
compared	0
with	0
timolol	1
solution	0
.	0

During	0
the	0
night	0
,	0
the	0
mean	0
12	0
-	0
hour	0
heart	0
rate	0
on	0
placebo	0
and	0
timolol	1
gellan	0
were	0
both	0
significantly	0
less	0
than	0
on	0
timolol	1
solution	0
;	0
the	0
difference	0
between	0
solution	0
and	0
gellan	0
treatments	0
was	0
statistically	0
significant	0
(	0
P	0
=	0
.	0
01	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Both	0
timolol	1
solution	0
and	0
timolol	1
gellan	0
decrease	0
the	0
mean	0
24	0
-	0
hour	0
heart	0
rate	0
compared	0
with	0
placebo	0
.	0

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

These	0
data	0
quantify	0
the	0
modest	0
bradycardia	3
associated	0
with	0
ophthalmic	0
beta	0
-	0
blocker	0
therapy	0
in	0
a	0
typical	0
patient	0
population	0
on	0
therapy	0
for	0
glaucoma	3
.	0

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

Management	0
strategies	0
for	0
ribavirin	1
-	0
induced	0
hemolytic	3
anemia	4
in	0
the	0
treatment	0
of	0
hepatitis	3
C	4
:	0
clinical	0
and	0
economic	0
implications	0
.	0

0BJECTIVES	0
:	0
Recently	0
published	0
studies	0
have	0
demonstrated	0
increased	0
efficacy	0
and	0
cost	0
-	0
effectiveness	0
of	0
combination	0
therapy	0
with	0
interferon	0
and	0
alpha	0
-	0
2b	0
/	0
ribavirin	1
compared	0
with	0
interferon	1
-	2
alpha	2
monotherapy	0
in	0
the	0
treatment	0
of	0
chronic	3
hepatitis	4
C	4
(	0
CHC	3
)	0
.	0

Combination	0
therapy	0
is	0
associated	0
with	0
a	0
clinically	0
important	0
adverse	0
effect	0
:	0
ribavirin	1
-	0
induced	0
hemolytic	3
anemia	4
(	0
RIHA	3
)	0
.	0

The	0
objective	0
of	0
this	0
study	0
was	0
to	0
evaluate	0
the	0
direct	0
health	0
-	0
care	0
costs	0
and	0
management	0
of	0
RIHA	3
during	0
treatment	0
of	0
CHC	3
in	0
a	0
clinical	0
trial	0
setting	0
.	0

METH0DS	0
:	0
A	0
systematic	0
literature	0
review	0
was	0
conducted	0
to	0
synthesize	0
information	0
on	0
the	0
incidence	0
and	0
management	0
of	0
RIHA	3
.	0

Decision	0
-	0
analytic	0
techniques	0
were	0
used	0
to	0
estimate	0
the	0
cost	0
of	0
treating	0
RIHA	3
.	0

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

RESULTS	0
:	0
RIHA	3
,	0
defined	0
as	0
a	0
reduction	0
in	0
hemoglobin	0
to	0
less	0
than	0
100	0
g	0
/	0
L	0
,	0
occurs	0
in	0
approximately	0
7	0
%	0
to	0
9	0
%	0
of	0
patients	0
treated	0
with	0
combination	0
therapy	0
.	0

The	0
standard	0
of	0
care	0
for	0
management	0
of	0
RIHA	3
is	0
reduction	0
or	0
discontinuation	0
of	0
the	0
ribavirin	1
dosage	0
.	0

We	0
estimated	0
the	0
direct	0
cost	0
of	0
treating	0
clinically	0
significant	0
RIHA	3
to	0
be	0
170	0
per	0
patient	0
receiving	0
combination	0
therapy	0
per	0
48	0
-	0
week	0
treatment	0
course	0
(	0
range	0
68	0
-	0
692	0
)	0
.	0

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

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

C0NCLUSI0NS	0
:	0
The	0
direct	0
cost	0
of	0
treating	0
clinically	0
significant	0
RIHA	3
is	0
1	0
%	0
(	0
170	0
/	0
16	0
,	0
459	0
)	0
of	0
drug	0
treatment	0
costs	0
.	0

Questions	0
remain	0
about	0
the	0
optimal	0
dose	0
of	0
ribavirin	1
and	0
the	0
incidence	0
of	0
RIHA	3
in	0
a	0
real	0
-	0
world	0
population	0
.	0

Despite	0
these	0
uncertainties	0
,	0
this	0
initial	0
evaluation	0
of	0
the	0
direct	0
cost	0
of	0
treating	0
RIHA	3
provides	0
an	0
estimate	0
of	0
the	0
cost	0
and	0
management	0
implications	0
of	0
this	0
clinically	0
important	0
adverse	0
effect	0
.	0

Preliminary	0
efficacy	0
assessment	0
of	0
intrathecal	0
injection	0
of	0
an	0
American	0
formulation	0
of	0
adenosine	1
in	0
humans	0
.	0

BACKGR0UND	0
:	0
Preclinical	0
studies	0
of	0
intrathecal	0
adenosine	1
suggest	0
it	0
may	0
be	0
effective	0
in	0
the	0
treatment	0
of	0
acute	3
and	4
chronic	4
pain	4
in	0
humans	0
,	0
and	0
preliminary	0
studies	0
in	0
volunteers	0
and	0
patients	0
with	0
a	0
Swedish	0
formulation	0
of	0
adenosine	1
suggests	0
it	0
may	0
be	0
effective	0
in	0
hypersensitivity	3
states	0
but	0
not	0
with	0
acute	0
noxious	0
stimulation	0
.	0

The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
screen	0
for	0
efficacy	0
of	0
a	0
different	0
formulation	0
of	0
adenosine	1
marketed	0
in	0
the	0
US	0
,	0
using	0
both	0
acute	0
noxious	0
stimulation	0
and	0
capsaicin	1
-	0
evoked	0
mechanical	0
hypersensitivity	3
.	0

METH0DS	0
:	0
Following	0
Food	0
and	0
Drug	0
Administration	0
and	0
institutional	0
review	0
board	0
approval	0
and	0
written	0
informed	0
consent	0
,	0
65	0
volunteers	0
were	0
studied	0
in	0
two	0
trials	0
:	0
an	0
open	0
-	0
label	0
,	0
dose	0
-	0
escalating	0
trial	0
with	0
intrathecal	0
adenosine	1
doses	0
of	0
0	0
.	0
25	0
-	0
2	0
.	0
0	0
mg	0
and	0
a	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
trial	0
of	0
adenosine	1
,	0
2	0
mg	0
.	0

Cerebrospinal	0
fluid	0
was	0
obtained	0
for	0
pharmacokinetic	0
analysis	0
,	0
and	0
pain	3
ratings	0
in	0
response	0
to	0
acute	0
heat	0
stimuli	0
and	0
areas	0
of	0
mechanical	3
hyperalgesia	4
and	0
allodynia	3
after	0
intradermal	0
capsaicin	1
injection	0
were	0
determined	0
.	0

RESULTS	0
:	0
Adenosine	1
produced	0
no	0
effect	0
on	0
pain	3
report	0
to	0
acute	0
noxious	0
thermal	0
or	0
chemical	0
stimulation	0
but	0
reduced	0
mechanical	3
hyperalgesia	4
and	0
allodynia	3
from	0
intradermal	0
capsaicin	1
injection	0
for	0
at	0
least	0
24	0
h	0
.	0

In	0
contrast	0
,	0
residence	0
time	0
of	0
adenosine	1
in	0
cerebrospinal	0
fluid	0
was	0
short	0
(	0
<	0
4	0
h	0
)	0
.	0

C0NCLUSI0NS	0
:	0
These	0
results	0
show	0
selective	0
inhibition	0
by	0
intrathecal	0
adenosine	1
of	0
hypersensitivity	3
,	0
presumed	0
to	0
reflect	0
central	0
sensitization	0
in	0
humans	0
after	0
peripheral	0
capsaicin	1
injection	0
.	0

The	0
long	0
-	0
lasting	0
effect	0
is	0
consistent	0
with	0
that	0
observed	0
in	0
preliminary	0
reports	0
of	0
patients	0
with	0
chronic	0
neuropathic	3
pain	4
and	0
is	0
not	0
due	0
to	0
prolonged	0
residence	0
of	0
adenosine	1
in	0
cerebrospinal	0
fluid	0
.	0

Delayed	0
-	0
onset	0
heparin	1
-	0
induced	0
thrombocytopenia	3
.	0

BACKGR0UND	0
:	0
Heparin	1
-	0
induced	0
thrombocytopenia	3
presents	0
5	0
to	0
12	0
days	0
after	0
heparin	1
exposure	0
,	0
with	0
or	0
without	0
arterial	3
or	4
venous	4
thromboemboli	4
.	0

Delayed	0
recognition	0
and	0
treatment	0
of	0
heparin	1
-	0
induced	0
thrombocytopenia	3
contribute	0
to	0
poor	0
patient	0
outcomes	0
.	0

0BJECTIVE	0
:	0
To	0
describe	0
and	0
increase	0
awareness	0
of	0
a	0
clinical	0
scenario	0
in	0
which	0
the	0
onset	0
or	0
manifestations	0
of	0
heparin	1
-	0
induced	0
thrombocytopenia	3
are	0
delayed	0
.	0

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

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

PATIENTS	0
:	0
14	0
patients	0
seen	0
over	0
a	0
3	0
-	0
year	0
period	0
in	0
whom	0
heparin	1
-	0
induced	0
thrombocytopenia	3
became	0
apparent	0
on	0
delayed	0
presentation	0
with	0
thromboembolic	3
complications	0
.	0

MEASUREMENTS	0
:	0
Platelet	0
counts	0
,	0
onset	0
of	0
objectively	0
determined	0
thromboembolism	3
,	0
results	0
of	0
heparin	1
-	0
induced	0
platelet	0
factor	0
4	0
antibody	0
tests	0
,	0
and	0
outcomes	0
.	0

RESULTS	0
:	0
Patients	0
went	0
home	0
after	0
hospitalizations	0
that	0
had	0
included	0
heparin	1
exposure	0
-	0
-	0
in	0
most	0
cases	0
,	0
with	0
no	0
thrombocytopenia	3
recognized	0
-	0
-	0
only	0
to	0
return	0
to	0
the	0
hospital	0
(	0
median	0
,	0
day	0
14	0
)	0
with	0
thromboembolic	3
complications	0
.	0

Thromboemboli	3
were	0
venous	0
(	0
12	0
patients	0
,	0
7	0
with	0
pulmonary	3
emboli	4
)	0
or	0
arterial	0
(	0
4	0
patients	0
)	0
or	0
both	0
.	0

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

0n	0
readmission	0
,	0
11	0
patients	0
received	0
therapeutic	0
heparin	1
,	0
which	0
worsened	0
the	0
patients	0
'	0
clinical	0
condition	0
and	0
,	0
in	0
all	0
11	0
cases	0
,	0
decreased	0
the	0
platelet	0
count	0
(	0
mean	0
at	0
readmission	0
,	0
143	0
x	0
10	0
(	0
9	0
)	0
cells	0
/	0
L	0
;	0
mean	0
nadir	0
after	0
heparin	1
re	0
-	0
exposure	0
,	0
39	0
x	0
10	0
(	0
9	0
)	0
cells	0
/	0
L	0
)	0
.	0

Results	0
of	0
serologic	0
tests	0
for	0
heparin	1
-	0
induced	0
antibodies	0
were	0
positive	0
in	0
all	0
patients	0
.	0

Subsequent	0
treatments	0
included	0
alternative	0
anticoagulants	0
(	0
11	0
patients	0
)	0
,	0
thrombolytic	0
drugs	0
(	0
3	0
patients	0
)	0
,	0
inferior	0
vena	0
cava	0
filters	0
(	0
3	0
patients	0
)	0
and	0
,	0
eventually	0
,	0
warfarin	1
(	0
11	0
patients	0
)	0
.	0

Three	0
patients	0
died	0
.	0

C0NCLUSI0NS	0
:	0
Delayed	0
-	0
onset	0
heparin	1
-	0
induced	0
thrombocytopenia	3
is	0
increasingly	0
being	0
recognized	0
.	0

To	0
avoid	0
disastrous	0
outcomes	0
,	0
physicians	0
must	0
consider	0
heparin	1
-	0
induced	0
thrombocytopenia	3
whenever	0
a	0
recently	0
hospitalized	0
patient	0
returns	0
with	0
thromboembolism	3
;	0
therapy	0
with	0
alternative	0
anticoagulants	0
,	0
not	0
heparin	1
,	0
should	0
be	0
initiated	0
.	0

Treatment	0
of	0
risperidone	1
-	0
induced	0
hyperprolactinemia	3
with	0
a	0
dopamine	1
agonist	0
in	0
children	0
.	0

BACKGR0UND	0
:	0
Risperidone	1
,	0
a	0
potent	0
antagonist	0
of	0
both	0
serotonergic	0
(	0
5HT2A	0
)	0
and	0
dopaminergic	0
D2	0
receptors	0
is	0
associated	0
with	0
hyperprolactinemia	3
in	0
adults	0
and	0
children	0
.	0

Chronically	0
elevated	0
prolactin	0
levels	0
in	0
children	0
with	0
prolactinomas	3
may	0
be	0
associated	0
with	0
arrested	0
growth	0
and	0
development	0
resulting	0
in	0
either	0
delayed	3
puberty	4
or	0
short	0
stature	0
.	0

These	0
possibilities	0
stress	0
the	0
importance	0
of	0
developing	0
a	0
safe	0
and	0
effective	0
approach	0
to	0
drug	0
-	0
induced	0
hyperprolactinemia	3
in	0
youth	0
.	0

We	0
report	0
the	0
successful	0
treatment	0
of	0
risperidone	1
-	0
induced	0
hyperprolactinemia	3
with	0
cabergoline	1
in	0
youth	0
.	0

METH0DS	0
:	0
We	0
undertook	0
a	0
retrospective	0
case	0
review	0
of	0
four	0
children	0
with	0
risperidone	1
-	0
induced	0
hyperprolactinemia	3
treated	0
with	0
cabergoline	1
.	0

RESULTS	0
:	0
Four	0
males	0
(	0
age	0
6	0
-	0
11	0
years	0
)	0
with	0
Diagnostic	0
and	0
Statistical	0
Manual	0
of	0
Mental	3
Disorders	4
(	0
fourth	0
edition	0
)	0
bipolar	3
disorder	4
or	0
psychoses	3
,	0
with	0
risperidone	1
-	0
induced	0
elevations	0
in	0
serum	0
prolactin	0
levels	0
(	0
57	0
.	0
5	0
-	0
129	0
ng	0
/	0
mL	0
,	0
normal	0
5	0
-	0
15	0
ng	0
/	0
mL	0
)	0
,	0
were	0
treated	0
with	0
cabergoline	1
(	0
mean	0
dose	0
2	0
.	0
13	0
+	0
/	0
-	0
0	0
.	0
09	0
mg	0
/	0
week	0
)	0
.	0

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

The	0
mean	0
duration	0
of	0
therapy	0
with	0
cabergoline	1
was	0
523	0
.	0
5	0
+	0
/	0
-	0
129	0
.	0
7	0
days	0
,	0
and	0
the	0
mean	0
duration	0
of	0
therapy	0
with	0
risperidone	1
was	0
788	0
.	0
5	0
+	0
/	0
-	0
162	0
.	0
5	0
days	0
.	0

Cabergoline	1
was	0
well	0
tolerated	0
without	0
adverse	0
effects	0
.	0

C0NCLUSI0NS	0
:	0
Cabergoline	1
may	0
be	0
useful	0
for	0
the	0
treatment	0
of	0
risperidone	1
-	0
induced	0
hyperprolactinemia	3
in	0
youth	0
;	0
however	0
,	0
further	0
research	0
is	0
needed	0
.	0

Acute	0
cholestatic	3
hepatitis	4
after	0
exposure	0
to	0
isoflurane	1
.	0

0BJECTIVE	0
:	0
To	0
report	0
a	0
case	0
of	0
acute	0
cholestatic	3
hepatitis	4
following	0
exposure	0
to	0
the	0
inhalational	0
anesthetic	0
isoflurane	1
.	0

CASE	0
SUMMARY	0
:	0
A	0
70	0
-	0
year	0
-	0
old	0
healthy	0
woman	0
from	0
Iraq	0
developed	0
acute	0
cholestatic	3
hepatitis	4
3	0
weeks	0
following	0
repair	0
of	0
the	0
right	0
rotator	0
cuff	0
under	0
general	0
anesthesia	0
.	0

There	0
was	0
no	0
evidence	0
for	0
viral	0
,	0
autoimmune	0
,	0
or	0
metabolic	0
causes	0
of	0
hepatitis	3
.	0

No	0
other	0
medications	0
were	0
involved	0
except	0
for	0
dipyrone	1
for	0
analgesia	3
.	0

The	0
alanine	1
aminotransferase	0
was	0
elevated	0
to	0
a	0
peak	0
concentration	0
of	0
1533	0
U	0
/	0
L	0
and	0
the	0
serum	0
bilirubin	1
reached	0
a	0
peak	0
of	0
17	0
.	0
0	0
mg	0
/	0
dL	0
.	0

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

Accidental	0
reexposure	0
by	0
the	0
patient	0
to	0
dipyrone	1
was	0
uneventful	0
.	0

DISCUSSI0N	0
:	0
The	0
clinical	0
and	0
histologic	0
picture	0
of	0
this	0
case	0
resembles	0
halothane	3
hepatitis	4
,	0
which	0
has	0
a	0
significant	0
mortality	0
rate	0
.	0

C0NCLUSI0NS	0
:	0
Isoflurane	1
,	0
a	0
common	0
anesthetic	0
agent	0
,	0
can	0
cause	0
severe	0
cholestatic	3
hepatitis	4
.	0

Torsade	3
de	4
pointes	4
induced	0
by	0
metoclopramide	1
in	0
an	0
elderly	0
woman	0
with	0
preexisting	0
complete	0
left	3
bundle	4
branch	4
block	4
.	0

There	0
is	0
a	0
growing	0
list	0
of	0
drugs	0
implicated	0
in	0
acquired	0
long	3
QT	4
syndrome	4
and	0
torsade	3
de	4
pointes	4
.	0

However	0
,	0
the	0
torsadogenic	0
potential	0
of	0
metoclopramide	1
,	0
a	0
commonly	0
used	0
antiemetic	0
and	0
prokinetic	0
drug	0
,	0
has	0
not	0
been	0
reported	0
in	0
the	0
literature	0
,	0
despite	0
its	0
chemical	0
similarity	0
to	0
procainamide	1
.	0

We	0
report	0
on	0
a	0
92	0
-	0
year	0
-	0
old	0
woman	0
with	0
preexisting	0
complete	0
left	3
bundle	4
branch	4
block	4
who	0
developed	0
torsade	3
de	4
pointes	4
after	0
intravenous	0
and	0
oral	0
administration	0
of	0
metoclopramide	1
.	0

This	0
patient	0
also	0
developed	0
torsade	3
de	4
pointes	4
when	0
cisapride	1
and	0
erythromycin	1
were	0
given	0
simultaneously	0
.	0

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

This	0
is	0
the	0
first	0
documentation	0
that	0
metoclopramide	1
provokes	0
torsade	3
de	4
pointes	4
clinically	0
.	0

Metoclopramide	1
should	0
be	0
used	0
cautiously	0
in	0
patients	0
with	0
a	0
risk	0
of	0
torsade	3
de	4
pointes	4
.	0

Dopamine	1
D2	0
receptor	0
signaling	0
controls	0
neuronal	0
cell	0
death	0
induced	0
by	0
muscarinic	0
and	0
glutamatergic	0
drugs	0
.	0

Dopamine	1
(	0
DA	1
)	0
,	0
through	0
D1	0
/	0
D2	0
receptor	0
-	0
mediated	0
signaling	0
,	0
plays	0
a	0
major	0
role	0
in	0
the	0
control	0
of	0
epileptic	3
seizures	4
arising	0
in	0
the	0
limbic	0
system	0
.	0

Excitotoxicity	3
leading	0
to	0
neuronal	0
cell	0
death	0
in	0
the	0
affected	0
areas	0
is	0
a	0
major	0
consequence	0
of	0
seizures	3
at	0
the	0
cellular	0
level	0
.	0

In	0
this	0
respect	0
,	0
little	0
is	0
known	0
about	0
the	0
role	0
of	0
DA	1
receptors	0
in	0
the	0
occurrence	0
of	0
epilepsy	3
-	0
induced	0
neuronal	0
cell	0
death	0
.	0

Here	0
we	0
analyze	0
the	0
occurrence	0
of	0
seizures	3
and	0
neurotoxicity	3
in	0
D2R	0
-	0
/	0
-	0
mice	0
treated	0
with	0
the	0
cholinergic	0
agonist	0
pilocarpine	1
.	0

We	0
compared	0
these	0
results	0
with	0
those	0
previously	0
obtained	0
with	0
kainic	1
acid	2
(	0
KA	1
)	0
,	0
a	0
potent	0
glutamate	1
agonist	0
.	0

Importantly	0
,	0
D2R	0
-	0
/	0
-	0
mice	0
develop	0
seizures	3
at	0
doses	0
of	0
both	0
drugs	0
that	0
are	0
not	0
epileptogenic	0
for	0
WT	0
littermates	0
and	0
show	0
greater	0
neurotoxicity	3
.	0

However	0
,	0
pilocarpine	1
-	0
induced	0
seizures	3
result	0
in	0
a	0
more	0
widespread	0
neuronal	0
death	0
in	0
both	0
WT	0
and	0
D2R	0
-	0
/	0
-	0
brains	0
in	0
comparison	0
to	0
KA	1
.	0

Thus	0
,	0
the	0
absence	0
of	0
D2R	0
lowers	0
the	0
threshold	0
for	0
seizures	3
induced	0
by	0
both	0
glutamate	1
and	0
acetylcholine	1
.	0

Moreover	0
,	0
the	0
dopaminergic	0
control	0
of	0
epilepsy	3
-	0
induced	0
neurodegeneration	3
seems	0
to	0
be	0
mediated	0
by	0
distinct	0
interactions	0
of	0
D2R	0
signaling	0
with	0
these	0
two	0
neurotransmitters	0
.	0

Steroid	1
structure	0
and	0
pharmacological	0
properties	0
determine	0
the	0
anti	0
-	0
amnesic	3
effects	0
of	0
pregnenolone	1
sulphate	2
in	0
the	0
passive	0
avoidance	0
task	0
in	0
rats	0
.	0

Pregnenolone	1
sulphate	2
(	0
PREGS	1
)	0
has	0
generated	0
interest	0
as	0
one	0
of	0
the	0
most	0
potent	0
memory	0
-	0
enhancing	0
neurosteroids	0
to	0
be	0
examined	0
in	0
rodent	0
learning	0
studies	0
,	0
with	0
particular	0
importance	0
in	0
the	0
ageing	0
process	0
.	0

The	0
mechanism	0
by	0
which	0
this	0
endogenous	0
steroid	1
enhances	0
memory	0
formation	0
is	0
hypothesized	0
to	0
involve	0
actions	0
on	0
glutamatergic	0
and	0
GABAergic	0
systems	0
.	0

This	0
hypothesis	0
stems	0
from	0
findings	0
that	0
PREGS	1
is	0
a	0
potent	0
positive	0
modulator	0
of	0
N	1
-	2
methyl	2
-	2
d	2
-	2
aspartate	2
receptors	0
(	0
NMDARs	0
)	0
and	0
a	0
negative	0
modulator	0
of	0
gamma	1
-	2
aminobutyric	2
acid	2
(	0
A	0
)	0
receptors	0
(	0
GABA	1
(	0
A	0
)	0
Rs	0
)	0
.	0

Moreover	0
,	0
PREGS	1
is	0
able	0
to	0
reverse	0
the	0
amnesic	3
-	0
like	0
effects	0
of	0
NMDAR	0
and	0
GABA	1
(	0
A	0
)	0
R	0
ligands	0
.	0

To	0
investigate	0
this	0
hypothesis	0
,	0
the	0
present	0
study	0
in	0
rats	0
examined	0
the	0
memory	0
-	0
altering	0
abilities	0
of	0
structural	0
analogs	0
of	0
PREGS	1
,	0
which	0
differ	0
in	0
their	0
modulation	0
of	0
NMDAR	0
and	0
/	0
or	0
GABA	1
(	0
A	0
)	0
R	0
function	0
.	0

The	0
analogs	0
tested	0
were	0
:	0
11	1
-	2
ketopregnenolone	2
sulphate	2
(	0
an	0
agent	0
that	0
is	0
inactive	0
at	0
GABA	1
(	0
A	0
)	0
Rs	0
and	0
NMDARs	0
)	0
,	0
epipregnanolone	1
(	2
[	2
3beta	2
-	2
hydroxy	2
-	2
5beta	2
-	2
pregnan	2
-	2
20	2
-	2
one	2
]	2
sulphate	2
,	0
an	0
inhibitor	0
of	0
both	0
GABA	1
(	0
A	0
)	0
Rs	0
and	0
NMDARs	0
)	0
,	0
and	0
a	0
newly	0
synthesized	0
(	0
-	0
)	0
PREGS	1
enantiomer	0
(	0
which	0
is	0
identical	0
to	0
PREGS	1
in	0
effects	0
on	0
GABA	1
(	0
A	0
)	0
Rs	0
and	0
NMDARs	0
)	0
.	0

The	0
memory	0
-	0
enhancing	0
effects	0
of	0
PREGS	1
and	0
its	0
analogs	0
were	0
tested	0
in	0
the	0
passive	0
avoidance	0
task	0
using	0
the	0
model	0
of	0
scopolamine	1
-	0
induced	0
amnesia	3
.	0

Both	0
PREGS	1
and	0
its	0
(	0
-	0
)	0
enantiomer	0
blocked	0
the	0
effects	0
of	0
scopolamine	1
.	0

The	0
results	0
show	0
that	0
,	0
unlike	0
PREGS	1
,	0
11	1
-	2
ketopregnenolone	2
sulphate	2
and	0
epipregnanolone	1
sulphate	2
failed	0
to	0
block	0
the	0
effect	0
of	0
scopolamine	1
,	0
suggesting	0
that	0
altering	0
the	0
modulation	0
of	0
NMDA	1
receptors	0
diminishes	0
the	0
memory	0
-	0
enhancing	0
effects	0
of	0
PREGS	1
.	0

Moreover	0
,	0
enantioselectivity	0
was	0
demonstrated	0
by	0
the	0
ability	0
of	0
natural	0
PREGS	1
to	0
be	0
an	0
order	0
of	0
magnitude	0
more	0
effective	0
than	0
its	0
synthetic	0
enantiomer	0
in	0
reversing	0
scopolamine	1
-	0
induced	0
amnesia	3
.	0

These	0
results	0
identify	0
a	0
novel	0
neuropharmacological	0
site	0
for	0
the	0
modulation	0
of	0
memory	0
processes	0
by	0
neuroactive	0
steroids	1
.	0

Activation	0
of	0
poly	1
(	2
ADP	2
-	2
ribose	2
)	2
polymerase	0
contributes	0
to	0
development	0
of	0
doxorubicin	1
-	0
induced	0
heart	3
failure	4
.	0

Activation	0
of	0
the	0
nuclear	0
enzyme	0
poly	1
(	2
ADP	2
-	2
ribose	2
)	2
polymerase	0
(	0
PARP	0
)	0
by	0
oxidant	0
-	0
mediated	0
DNA	0
damage	0
is	0
an	0
important	0
pathway	0
of	0
cell	0
dysfunction	0
and	0
tissue	0
injury	0
in	0
conditions	0
associated	0
with	0
oxidative	0
stress	0
.	0

Increased	0
oxidative	0
stress	0
is	0
a	0
major	0
factor	0
implicated	0
in	0
the	0
cardiotoxicity	3
of	0
doxorubicin	1
(	0
D0X	1
)	0
,	0
a	0
widely	0
used	0
antitumor	0
anthracycline	1
antibiotic	0
.	0

Thus	0
,	0
we	0
hypothesized	0
that	0
the	0
activation	0
of	0
PARP	0
may	0
contribute	0
to	0
the	0
D0X	1
-	0
induced	0
cardiotoxicity	3
.	0

Using	0
a	0
dual	0
approach	0
of	0
PARP	0
-	0
1	0
suppression	0
,	0
by	0
genetic	0
deletion	0
or	0
pharmacological	0
inhibition	0
with	0
the	0
phenanthridinone	0
PARP	0
inhibitor	0
PJ34	1
,	0
we	0
now	0
demonstrate	0
the	0
role	0
of	0
PARP	0
in	0
the	0
development	0
of	0
cardiac	3
dysfunction	4
induced	0
by	0
D0X	1
.	0

PARP	0
-	0
1	0
+	0
/	0
+	0
and	0
PARP	0
-	0
1	0
-	0
/	0
-	0
mice	0
received	0
a	0
single	0
injection	0
of	0
D0X	1
(	0
25	0
mg	0
/	0
kg	0
i	0
.	0
p	0
)	0
.	0

Five	0
days	0
after	0
D0X	1
administration	0
,	0
left	0
ventricular	0
performance	0
was	0
significantly	0
depressed	0
in	0
PARP	0
-	0
1	0
+	0
/	0
+	0
mice	0
,	0
but	0
only	0
to	0
a	0
smaller	0
extent	0
in	0
PARP	0
-	0
1	0
-	0
/	0
-	0
ones	0
.	0

Similar	0
experiments	0
were	0
conducted	0
in	0
BALB	0
/	0
c	0
mice	0
treated	0
with	0
PJ34	1
or	0
vehicle	0
.	0

Treatment	0
with	0
a	0
PJ34	1
significantly	0
improved	0
cardiac	3
dysfunction	4
and	0
increased	0
the	0
survival	0
of	0
the	0
animals	0
.	0

In	0
addition	0
PJ34	1
significantly	0
reduced	0
the	0
D0X	1
-	0
induced	0
increase	0
in	0
the	0
serum	0
lactate	1
dehydrogenase	0
and	0
creatine	1
kinase	0
activities	0
but	0
not	0
metalloproteinase	0
activation	0
in	0
the	0
heart	0
.	0

Thus	0
,	0
PARP	0
activation	0
contributes	0
to	0
the	0
cardiotoxicity	3
of	0
D0X	1
.	0

PARP	0
inhibitors	0
may	0
exert	0
protective	0
effects	0
against	0
the	0
development	0
of	0
severe	0
cardiac	3
complications	4
associated	0
with	0
the	0
D0X	1
treatment	0
.	0

Spironolactone	1
:	0
is	0
it	0
a	0
novel	0
drug	0
for	0
the	0
prevention	0
of	0
amphotericin	1
B	2
-	0
related	0
hypokalemia	3
in	0
cancer	3
patients	0
?	0

0BJECTIVE	0
:	0
Nephrotoxicity	3
is	0
the	0
major	0
adverse	0
effect	0
of	0
amphotericin	1
B	2
(	0
AmB	1
)	0
,	0
often	0
limiting	0
administration	0
of	0
full	0
dosage	0
.	0

Selective	0
distal	0
tubular	0
epithelial	0
toxicity	3
seems	0
to	0
be	0
responsible	0
for	0
the	0
profound	0
potassium	1
wasting	0
that	0
is	0
a	0
major	0
clinical	0
side	0
effect	0
of	0
treatment	0
with	0
AmB	1
.	0

Potassium	1
depletion	0
also	0
potentiates	0
the	0
tubular	0
toxicity	3
of	0
AmB	1
.	0

This	0
study	0
was	0
designed	0
to	0
assess	0
the	0
ability	0
of	0
spironolactone	1
to	0
reduce	0
potassium	1
requirements	0
and	0
to	0
prevent	0
hypokalemia	3
in	0
neutropenic	3
patients	0
on	0
AmB	1
treatment	0
.	0

METH0DS	0
:	0
In	0
this	0
study	0
26	0
patients	0
with	0
various	0
hematological	3
disorders	4
were	0
randomized	0
to	0
receive	0
either	0
intravenous	0
AmB	1
alone	0
or	0
AmB	1
and	0
oral	0
spironolactone	1
100	0
mg	0
twice	0
daily	0
when	0
developing	0
a	0
proven	0
or	0
suspected	0
fungal	3
infection	4
.	0

RESULTS	0
:	0
Patients	0
receiving	0
concomitant	0
AmB	1
and	0
spironolactone	1
had	0
significantly	0
higher	0
plasma	0
potassium	1
levels	0
than	0
those	0
receiving	0
AmB	1
alone	0
(	0
P	0
=	0
0	0
.	0
0027	0
)	0
.	0

Those	0
patients	0
receiving	0
AmB	1
and	0
spironolactone	1
required	0
significantly	0
less	0
potassium	1
supplementation	0
to	0
maintain	0
their	0
plasma	0
potassium	1
within	0
the	0
normal	0
range	0
(	0
P	0
=	0
0	0
.	0
022	0
)	0
.	0

Moreover	0
,	0
urinary	0
potassium	1
losses	0
were	0
significantly	0
less	0
in	0
patients	0
receiving	0
AmB	1
and	0
spironolactone	1
than	0
those	0
receiving	0
AmB	1
alone	0
(	0
P	0
=	0
0	0
.	0
040	0
)	0
.	0

C0NCLUSI0N	0
:	0
This	0
study	0
showed	0
that	0
spironolactone	1
can	0
reduce	0
potassium	1
requirements	0
and	0
prevent	0
hypokalemia	3
by	0
reducing	0
urinary	0
potassium	1
loss	0
in	0
neutropenic	3
patients	0
on	0
AmB	1
treatment	0
.	0

Erectile	3
dysfunction	4
occurs	0
following	0
substantia	0
nigra	0
lesions	0
in	0
the	0
rat	0
.	0

Erectile	0
function	0
was	0
assessed	0
6	0
weeks	0
following	0
uni	0
-	0
and	0
bilateral	0
injections	0
of	0
6	1
-	2
hydroxydopamine	2
in	0
the	0
substantia	0
nigra	0
nucleus	0
of	0
the	0
brain	0
.	0

Behavioral	0
apomorphine	1
-	0
induced	0
penile	0
erections	0
were	0
reduced	0
(	0
5	0
/	0
8	0
)	0
and	0
increased	0
(	0
3	0
/	0
8	0
)	0
in	0
uni	0
-	0
and	0
bilateral	0
lesioned	0
animals	0
.	0

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

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

Concentration	0
of	0
dopamine	1
and	0
its	0
metabolites	0
were	0
decreased	0
in	0
the	0
striatum	0
of	0
substantia	0
nigra	0
lesioned	0
rats	0
.	0

Lesions	0
of	0
the	0
substantia	0
nigra	0
are	0
therefore	0
associated	0
with	0
erectile	3
dysfunction	4
in	0
rats	0
and	0
may	0
serve	0
as	0
a	0
model	0
to	0
study	0
erectile	3
dysfunction	4
in	0
Parkinson	3
'	4
s	4
disease	4
.	0

Nicotine	1
potentiation	0
of	0
morphine	1
-	0
induced	0
catalepsy	3
in	0
mice	0
.	0

In	0
the	0
present	0
study	0
,	0
effects	0
of	0
nicotine	1
on	0
catalepsy	3
induced	0
by	0
morphine	1
in	0
mice	0
have	0
been	0
investigated	0
.	0

Morphine	1
but	0
not	0
nicotine	1
induced	0
a	0
dose	0
-	0
dependent	0
catalepsy	3
.	0

The	0
response	0
of	0
morphine	1
was	0
potentiated	0
by	0
nicotine	1
.	0

Intraperitoneal	0
administration	0
of	0
atropine	1
,	0
naloxone	1
,	0
mecamylamine	1
,	0
and	0
hexamethonium	1
to	0
mice	0
reduced	0
catalepsy	3
induced	0
by	0
a	0
combination	0
of	0
morphine	1
with	0
nicotine	1
.	0

Intracerebroventricular	0
injection	0
of	0
atropine	1
,	0
hexamethonium	1
,	0
and	0
naloxone	1
also	0
decreased	0
catalepsy	3
induced	0
by	0
morphine	1
plus	0
nicotine	1
.	0

Intraperitoneal	0
administration	0
of	0
atropine	1
,	0
but	0
not	0
intraperitoneal	0
or	0
intracerebroventricular	0
injection	0
of	0
hexamethonium	1
,	0
decreased	0
the	0
effect	0
of	0
a	0
single	0
dose	0
of	0
morphine	1
.	0

It	0
was	0
concluded	0
that	0
morphine	1
catalepsy	3
can	0
be	0
elicited	0
by	0
opioid	0
and	0
cholinergic	0
receptors	0
,	0
and	0
the	0
potentiation	0
of	0
morphine	1
induced	0
by	0
nicotine	1
may	0
also	0
be	0
mediated	0
through	0
cholinergic	0
receptor	0
mechanisms	0
.	0

Force	0
overflow	0
and	0
levodopa	1
-	0
induced	0
dyskinesias	3
in	0
Parkinson	3
'	4
s	4
disease	4
.	0

We	0
assessed	0
force	0
coordination	0
of	0
the	0
hand	0
in	0
Parkinson	3
'	4
s	4
disease	4
and	0
its	0
relationship	0
to	0
motor	0
complications	0
of	0
levodopa	1
therapy	0
,	0
particularly	0
to	0
levodopa	1
-	0
induced	0
dyskinesias	3
(	0
LID	3
)	0
.	0

We	0
studied	0
two	0
groups	0
of	0
Parkinson	3
'	4
s	4
disease	4
patients	0
with	0
(	0
Parkinson	3
'	4
s	4
disease	4
+	0
LID	3
,	0
n	0
=	0
23	0
)	0
and	0
without	0
levodopa	1
-	0
induced	0
dyskinesias	3
(	0
Parkinson	3
'	4
s	4
disease	4
-	0
LID	3
,	0
n	0
=	0
10	0
)	0
,	0
and	0
age	0
-	0
matched	0
healthy	0
controls	0
.	0

The	0
motor	0
score	0
of	0
the	0
Unified	0
Parkinson	3
'	4
s	4
Disease	4
Rating	0
Scale	0
,	0
a	0
dyskinesia	3
score	0
and	0
force	0
in	0
a	0
grip	0
-	0
lift	0
paradigm	0
were	0
assessed	0
0N	0
and	0
0FF	0
levodopa	1
.	0

A	0
pathological	0
increase	0
of	0
forces	0
was	0
seen	0
in	0
0N	0
-	0
state	0
in	0
Parkinson	3
'	4
s	4
disease	4
+	0
LID	3
only	0
.	0

In	0
Parkinson	3
'	4
s	4
disease	4
+	0
LID	3
,	0
the	0
force	0
involved	0
in	0
pressing	0
down	0
the	0
object	0
before	0
lifting	0
was	0
significantly	0
increased	0
by	0
levodopa	1
(	0
by	0
61	0
%	0
,	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

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

In	0
contrast	0
,	0
no	0
excessive	0
force	0
was	0
found	0
in	0
Parkinson	3
'	4
s	4
disease	4
-	0
LID	3
.	0

Peak	0
grip	0
force	0
in	0
0N	0
-	0
state	0
was	0
140	0
%	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
higher	0
in	0
Parkinson	3
'	4
s	4
disease	4
+	0
LID	3
than	0
in	0
Parkinson	3
'	4
s	4
disease	4
-	0
LID	3
,	0
while	0
static	0
grip	0
force	0
was	0
increased	0
by	0
138	0
%	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
between	0
groups	0
.	0

Severity	0
of	0
peak	0
-	0
dose	0
dyskinesias	3
was	0
strongly	0
correlated	0
with	0
grip	0
force	0
in	0
0N	0
-	0
state	0
(	0
r	0
=	0
0	0
.	0
79	0
with	0
peak	0
force	0
,	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

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

Force	0
excess	0
was	0
only	0
observed	0
in	0
patients	0
with	0
LID	3
and	0
motor	0
fluctuations	0
.	0

A	0
close	0
relationship	0
was	0
seen	0
between	0
the	0
overshooting	0
of	0
forces	0
and	0
dyskinesias	3
in	0
the	0
0N	0
-	0
drug	0
condition	0
.	0

We	0
postulate	0
that	0
both	0
LID	3
and	0
grip	0
force	0
excess	0
share	0
common	0
pathophysiological	0
mechanisms	0
related	0
to	0
motor	0
fluctuations	0
.	0

Behavioral	0
effects	0
of	0
MK	1
-	2
801	2
on	0
reserpine	1
-	0
treated	0
mice	0
.	0

The	0
effects	0
of	0
dizocilpine	1
(	0
MK	1
-	2
801	2
)	0
,	0
a	0
noncompetitive	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
(	0
NMDA	1
)	0
receptor	0
antagonist	0
,	0
were	0
studied	0
on	0
dopamine	1
-	0
related	0
behaviors	0
induced	0
by	0
reserpine	1
treatments	0
.	0

This	0
study	0
focuses	0
on	0
behavioral	0
syndromes	0
that	0
may	0
used	0
as	0
models	0
for	0
Parkinson	3
'	4
s	4
disease	4
,	0
or	0
tardive	3
dyskinesia	4
,	0
and	0
its	0
response	0
after	0
glutamatergic	0
blockage	0
.	0

Reserpine	1
(	0
1	0
mg	0
/	0
kg	0
)	0
,	0
administered	0
once	0
every	0
other	0
day	0
for	0
4	0
days	0
,	0
produced	0
increases	0
in	0
orofacial	3
dyskinesia	4
,	0
tongue	0
protrusion	0
and	0
vacuous	0
chewing	0
in	0
mice	0
,	0
which	0
are	0
signs	0
indicative	0
of	0
tardive	3
dyskinesia	4
.	0

Reserpine	1
also	0
produced	0
tremor	3
and	0
catalepsy	3
,	0
which	0
are	0
signs	0
suggestive	0
of	0
Parkinson	3
'	4
s	4
disease	4
.	0

MK	1
-	2
801	2
(	0
0	0
.	0
1	0
mg	0
/	0
kg	0
)	0
,	0
administered	0
30	0
min	0
before	0
the	0
observation	0
test	0
,	0
prevented	0
the	0
vacuous	0
chewing	0
movements	0
,	0
tongue	0
protrusions	0
and	0
catalepsy	3
induced	0
by	0
reserpine	1
.	0

However	0
,	0
MK	1
-	2
801	2
injection	0
produced	0
a	0
significant	0
increase	0
of	0
tremor	3
in	0
reserpine	1
-	0
treated	0
mice	0
.	0

Reserpine	1
(	0
1	0
mg	0
/	0
kg	0
)	0
,	0
administered	0
90	0
min	0
before	0
the	0
test	0
and	0
followed	0
by	0
apomophine	1
injection	0
(	0
0	0
.	0
1	0
mg	0
/	0
kg	0
)	0
5	0
min	0
before	0
the	0
test	0
,	0
did	0
not	0
produce	0
oral	3
dyskinesia	4
in	0
mice	0
.	0

0n	0
the	0
other	0
hand	0
,	0
reserpine	1
induced	0
increases	0
in	0
tremor	3
and	0
catalepsy	3
compared	0
to	0
control	0
mice	0
.	0

MK	1
-	2
801	2
(	0
0	0
.	0
1	0
mg	0
/	0
kg	0
)	0
administration	0
attenuated	0
the	0
catalepsy	3
and	0
tremor	3
induced	0
by	0
reserpine	1
.	0

Pretreatment	0
with	0
reserpine	1
(	0
1	0
mg	0
/	0
kg	0
)	0
24	0
h	0
before	0
the	0
observation	0
test	0
produced	0
increases	0
in	0
vacuous	0
chewing	0
movements	0
and	0
tongue	0
protrusion	0
,	0
as	0
well	0
as	0
increases	0
in	0
tremor	3
and	0
catalepsy	3
,	0
whereas	0
MK	1
-	2
801	2
(	0
0	0
.	0
1	0
mg	0
/	0
kg	0
)	0
injection	0
90	0
min	0
before	0
the	0
test	0
reversed	0
the	0
effects	0
of	0
reserpine	1
.	0

These	0
results	0
show	0
that	0
reserpine	1
produces	0
different	0
and	0
abnormal	3
movements	4
,	0
which	0
are	0
related	0
to	0
dose	0
and	0
schedule	0
employed	0
and	0
can	0
be	0
considered	0
as	0
parkinsonian	3
-	0
like	0
and	0
tardive	3
dsykinesia	4
signs	0
.	0

The	0
glutamatergic	0
blockage	0
produced	0
by	0
NMDA	1
can	0
restore	0
these	0
signs	0
,	0
such	0
as	0
vacuous	0
chewing	0
movements	0
,	0
tongue	0
protrusions	0
,	0
catalepsy	3
and	0
tremor	3
according	0
to	0
the	0
employed	0
model	0
.	0

Risperidone	1
-	0
associated	0
,	0
benign	0
transient	0
visual	3
disturbances	4
in	0
schizophrenic	3
patients	0
with	0
a	0
past	0
history	0
of	0
LSD	1
abuse	0
.	0

Two	0
schizophrenic	3
patients	0
,	0
who	0
had	0
a	0
prior	0
history	0
of	0
LSD	1
abuse	0
and	0
who	0
had	0
previously	0
developed	0
EPS	3
with	0
classic	0
antipsychotics	0
,	0
were	0
successfully	0
treated	0
with	0
risperidone	1
.	0

They	0
both	0
reported	0
short	0
episodes	0
of	0
transient	0
visual	3
disturbances	4
,	0
which	0
appeared	0
immediately	0
after	0
starting	0
treatment	0
with	0
risperidone	1
.	0

This	0
imagery	0
resembled	0
visual	3
disturbances	4
previously	0
experienced	0
as	0
"	0
flashbacks	0
"	0
related	0
to	0
prior	0
LSD	1
consumption	0
.	0

Risperidone	1
administration	0
was	0
continued	0
and	0
the	0
visual	3
disturbances	4
gradually	0
wore	0
off	0
.	0

During	0
a	0
six	0
-	0
month	0
follow	0
-	0
up	0
period	0
,	0
there	0
was	0
no	0
recurrence	0
of	0
visual	3
disturbances	4
.	0

This	0
phenomenon	0
may	0
be	0
interpreted	0
as	0
a	0
benign	0
,	0
short	0
-	0
term	0
and	0
self	0
-	0
limiting	0
side	0
effect	0
which	0
does	0
not	0
contraindicate	0
the	0
use	0
of	0
risperidone	1
or	0
interfere	0
with	0
treatment	0
.	0

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

Topiramate	1
-	0
induced	0
nephrolithiasis	3
.	0

Topiramate	1
is	0
a	0
recently	0
developed	0
antiepileptic	0
medication	0
that	0
is	0
becoming	0
more	0
widely	0
prescribed	0
because	0
of	0
its	0
efficacy	0
in	0
treating	0
refractory	3
seizures	4
.	0

Urologists	0
should	0
be	0
aware	0
that	0
this	0
medication	0
can	0
cause	0
metabolic	3
acidosis	4
in	0
patients	0
secondary	0
to	0
inhibition	0
of	0
carbonic	0
anhydrase	0
.	0

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

These	0
factors	0
can	0
lead	0
to	0
the	0
development	0
of	0
calcium	1
phosphate	2
nephrolithiasis	3
.	0

We	0
report	0
the	0
first	0
two	0
cases	0
of	0
topiramate	1
-	0
induced	0
nephrolithiasis	3
in	0
the	0
urologic	0
literature	0
.	0

Ketamine	1
in	0
war	0
/	0
tropical	0
surgery	0
(	0
a	0
final	0
tribute	0
to	0
the	0
racemic	0
mixture	0
)	0
.	0

A	0
technique	0
of	0
continuous	0
intravenous	0
anaesthesia	0
with	0
ketamine	1
was	0
used	0
successfully	0
during	0
the	0
Somalia	0
civil	0
war	0
in	0
1994	0
and	0
in	0
north	0
Uganda	0
in	0
1999	0
for	0
64	0
operations	0
in	0
62	0
patients	0
,	0
aged	0
from	0
6	0
weeks	0
to	0
70	0
years	0
,	0
undergoing	0
limb	0
and	0
abdominal	0
surgery	0
including	0
caesarian	0
sections	0
and	0
interventions	0
in	0
neonates	0
.	0

0perations	0
lasting	0
up	0
to	0
2h	0
could	0
be	0
performed	0
in	0
the	0
absence	0
of	0
sophisticated	0
equipment	0
such	0
as	0
pulse	0
oximeters	0
or	0
ventilators	0
in	0
patients	0
on	0
spontaneous	0
ventilation	0
breathing	0
air	0
/	0
oxygen	1
only	0
.	0

After	0
premedication	0
with	0
diazepam	1
,	0
glycopyrrolate	1
and	0
local	0
anaesthesia	0
,	0
and	0
induction	0
with	0
standard	0
doses	0
of	0
ketamine	1
,	0
a	0
maintenance	0
dose	0
of	0
10	0
-	0
20	0
microg	0
/	0
kg	0
/	0
min	0
of	0
ketamine	1
proved	0
safe	0
and	0
effective	0
.	0

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

Diazepam	1
,	0
unless	0
contraindicated	0
or	0
risky	0
,	0
remains	0
the	0
only	0
necessary	0
complementary	0
drug	0
to	0
ketamine	1
as	0
it	0
buffers	0
its	0
cardiovascular	0
response	0
and	0
decreases	0
the	0
duration	0
and	0
intensity	0
of	0
operative	0
and	0
postoperative	0
hallucinations	3
.	0

Local	0
anaesthetic	0
blocks	0
were	0
useful	0
in	0
decreasing	0
the	0
requirement	0
for	0
postoperative	0
analgesia	3
.	0

An	0
antisialogue	0
was	0
usually	0
unnecessary	0
in	0
operations	0
lasting	0
up	0
to	0
2	0
h	0
,	0
glycopyrrolate	1
being	0
the	0
best	0
choice	0
for	0
its	0
lowest	0
psychotropic	0
and	0
chronotropic	0
effects	0
,	0
especially	0
in	0
a	0
hot	0
climate	0
.	0

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

Intravenous	0
ribavirin	1
treatment	0
for	0
severe	0
adenovirus	3
disease	4
in	0
immunocompromised	0
children	0
.	0

BACKGR0UND	0
:	0
Adenovirus	0
is	0
an	0
important	0
cause	0
of	0
morbidity	0
and	0
mortality	0
in	0
the	0
immunocompromised	0
host	0
.	0

The	0
incidence	0
of	0
severe	0
adenovirus	3
disease	4
in	0
pediatrics	0
is	0
increasing	0
in	0
association	0
with	0
growing	0
numbers	0
of	0
immunocompromised	0
children	0
,	0
where	0
case	0
fatality	0
rates	0
as	0
high	0
as	0
50	0
%	0
to	0
80	0
%	0
have	0
been	0
reported	0
.	0

There	0
are	0
no	0
approved	0
antiviral	0
agents	0
with	0
proven	0
efficacy	0
for	0
the	0
treatment	0
of	0
severe	0
adenovirus	3
disease	4
,	0
nor	0
are	0
there	0
any	0
prospective	0
randomized	0
,	0
controlled	0
trials	0
of	0
potentially	0
useful	0
anti	0
-	0
adenovirus	0
therapies	0
.	0

Apparent	0
clinical	0
success	0
in	0
the	0
treatment	0
of	0
severe	0
adenovirus	3
disease	4
is	0
limited	0
to	0
a	0
few	0
case	0
reports	0
and	0
small	0
series	0
.	0

Experience	0
is	0
greatest	0
with	0
intravenous	0
ribavirin	1
and	0
cidofovir	1
.	0

Ribavirin	1
,	0
a	0
guanosine	1
analogue	0
,	0
has	0
broad	0
antiviral	0
activity	0
against	0
both	0
RNA	0
and	0
DNA	0
viruses	0
,	0
including	0
documented	0
activity	0
against	0
adenovirus	0
in	0
vitro	0
.	0

Ribavirin	1
is	0
licensed	0
in	0
aerosol	0
form	0
for	0
the	0
treatment	0
of	0
respiratory	3
syncytial	4
virus	4
infection	4
,	0
and	0
orally	0
in	0
combination	0
with	0
interferon	0
to	0
treat	0
hepatitis	3
C	4
.	0

Intravenous	0
ribavirin	1
is	0
the	0
treatment	0
of	0
choice	0
for	0
infection	3
with	4
hemorrhagic	4
fever	4
viruses	4
.	0

The	0
most	0
common	0
adverse	0
effect	0
of	0
intravenous	0
ribavirin	1
is	0
reversible	0
mild	0
anemia	3
.	0

The	0
use	0
of	0
cidofovir	1
in	0
severe	0
adenovirus	3
infection	4
has	0
been	0
limited	0
by	0
adverse	0
effects	0
,	0
the	0
most	0
significant	0
of	0
which	0
is	0
nephrotoxicity	3
.	0

0BJECTIVE	0
:	0
We	0
report	0
our	0
experience	0
with	0
intravenous	0
ribavirin	1
therapy	0
for	0
severe	0
adenovirus	3
disease	4
in	0
a	0
series	0
of	0
immunocompromised	0
children	0
and	0
review	0
the	0
literature	0
.	0

DESIGN	0
/	0
METH0DS	0
:	0
We	0
retrospectively	0
reviewed	0
the	0
medical	0
records	0
of	0
5	0
children	0
treated	0
with	0
intravenous	0
ribavirin	1
for	0
documented	0
severe	0
adenovirus	3
disease	4
.	0

Two	0
patients	0
developed	0
adenovirus	0
hemorrhagic	3
cystitis	4
after	0
cardiac	0
and	0
bone	0
marrow	0
transplants	0
,	0
respectively	0
.	0

The	0
bone	0
marrow	0
transplant	0
patient	0
also	0
received	0
intravenous	0
cidofovir	1
for	0
progressive	0
disseminated	0
disease	0
.	0

An	0
additional	0
3	0
children	0
developed	0
adenovirus	3
pneumonia	4
;	0
2	0
were	0
neonates	0
,	0
1	0
of	0
whom	0
had	0
partial	0
DiGeorge	3
syndrome	4
.	0

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

Intravenous	0
ribavirin	1
was	0
administered	0
on	0
a	0
compassionate	0
-	0
use	0
protocol	0
.	0

RESULTS	0
:	0
Complete	0
clinical	0
recovery	0
followed	0
later	0
by	0
viral	0
clearance	0
was	0
observed	0
in	0
2	0
children	0
:	0
the	0
cardiac	0
transplant	0
recipient	0
with	0
adenovirus	0
hemorrhagic	3
cystitis	4
and	0
the	0
immunocompetent	0
neonate	0
with	0
adenovirus	3
pneumonia	4
.	0

The	0
remaining	0
3	0
children	0
died	0
of	0
adenovirus	3
disease	4
.	0

Intravenous	0
ribavirin	1
therapy	0
was	0
well	0
tolerated	0
.	0

Use	0
of	0
cidofovir	1
in	0
1	0
child	0
was	0
associated	0
with	0
progressive	3
renal	4
failure	4
and	0
neutropenia	3
.	0

DISCUSSI0N	0
:	0
0ur	0
series	0
of	0
patients	0
is	0
representative	0
of	0
the	0
spectrum	0
of	0
immunocompromised	0
children	0
at	0
greatest	0
risk	0
for	0
severe	0
adenovirus	3
disease	4
,	0
namely	0
solid	0
-	0
organ	0
and	0
bone	0
marrow	0
transplant	0
recipients	0
,	0
neonates	0
,	0
and	0
children	0
with	0
immunodeficiency	3
.	0

Although	0
intravenous	0
ribavirin	1
was	0
not	0
effective	0
for	0
all	0
children	0
with	0
severe	0
adenovirus	3
disease	4
in	0
this	0
series	0
or	0
in	0
the	0
literature	0
,	0
therapy	0
is	0
unlikely	0
to	0
be	0
of	0
benefit	0
if	0
begun	0
late	0
in	0
the	0
course	0
of	0
the	0
infection	3
.	0

Early	0
identification	0
,	0
eg	0
by	0
polymerase	0
chain	0
reaction	0
of	0
those	0
patients	0
at	0
risk	0
of	0
disseminated	0
adenovirus	3
disease	4
may	0
permit	0
earlier	0
antiviral	0
treatment	0
and	0
better	0
evaluation	0
of	0
therapeutic	0
response	0
.	0

C0NCLUSI0NS	0
:	0
Two	0
of	0
5	0
children	0
with	0
severe	0
adenovirus	3
disease	4
treated	0
with	0
intravenous	0
ribavirin	1
recovered	0
.	0

The	0
availability	0
of	0
newer	0
rapid	0
diagnostic	0
techniques	0
,	0
such	0
as	0
polymerase	0
chain	0
reaction	0
,	0
may	0
make	0
earlier	0
,	0
more	0
effective	0
treatment	0
of	0
adenovirus	3
infection	4
possible	0
.	0

Given	0
the	0
seriousness	0
and	0
increasing	0
prevalence	0
of	0
adenovirus	3
disease	4
in	0
certain	0
hosts	0
,	0
especially	0
children	0
,	0
a	0
large	0
,	0
multicenter	0
clinical	0
trial	0
of	0
potentially	0
useful	0
anti	0
-	0
adenoviral	0
therapies	0
,	0
such	0
as	0
intravenous	0
ribavirin	1
,	0
is	0
clearly	0
required	0
to	0
demonstrate	0
the	0
most	0
effective	0
and	0
least	0
toxic	0
therapy	0
.	0

Delayed	0
asystolic	3
cardiac	3
arrest	4
after	0
diltiazem	1
overdose	3
;	0
resuscitation	0
with	0
high	0
dose	0
intravenous	0
calcium	1
.	0

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

He	0
initially	0
presented	0
to	0
hospital	0
after	0
six	0
hours	0
with	0
mild	0
hypotension	3
and	0
was	0
treated	0
with	0
activated	0
charcoal	0
and	0
intravenous	0
fluids	0
.	0

Eighteen	0
hours	0
after	0
the	0
overdose	3
he	0
had	0
two	0
generalised	0
tonic	3
-	4
clonic	4
seizures	4
.	0

The	0
patient	0
remained	0
unresponsive	0
with	0
junctional	0
bradycardia	3
,	0
unrecordable	0
blood	0
pressure	0
,	0
and	0
then	0
became	0
asystolic	3
.	0

He	0
was	0
resuscitated	0
with	0
high	0
dose	0
(	0
13	0
.	0
5	0
g	0
)	0
intravenous	0
calcium	1
and	0
adrenaline	1
(	0
epinephrine	1
)	0
.	0

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

This	0
case	0
suggests	0
there	0
is	0
a	0
role	0
for	0
aggressive	0
high	0
dose	0
intravenous	0
calcium	1
therapy	0
in	0
severe	0
diltiazem	1
overdose	3
,	0
particularly	0
with	0
the	0
onset	0
of	0
asystole	3
.	0

It	0
should	0
be	0
considered	0
early	0
in	0
cases	0
of	0
cardiac	3
arrest	4
after	0
diltiazem	1
overdose	3
.	0

The	0
case	0
also	0
highlights	0
the	0
problems	0
with	0
delayed	0
toxicity	3
when	0
whole	0
bowel	0
irrigation	0
is	0
not	0
administered	0
.	0

Low	1
-	2
molecular	2
-	2
weight	2
heparin	2
for	0
the	0
treatment	0
of	0
patients	0
with	0
mechanical	0
heart	0
valves	0
.	0

BACKGR0UND	0
:	0
The	0
interruption	0
of	0
oral	0
anticoagulant	0
(	0
0AC	0
)	0
administration	0
is	0
sometimes	0
indicated	0
in	0
patients	0
with	0
mechanical	0
heart	0
valves	0
,	0
mainly	0
before	0
noncardiac	0
surgery	0
,	0
non	0
-	0
surgical	0
interventions	0
,	0
and	0
pregnancy	0
.	0

Unfractionated	1
heparin	2
(	0
UH	1
)	0
is	0
currently	0
the	0
substitute	0
for	0
selected	0
patients	0
.	0

Low	1
-	2
molecular	2
-	2
weight	2
heparin	2
(	0
LMWH	1
)	0
offers	0
theoretical	0
advantages	0
over	0
UH	1
,	0
but	0
is	0
not	0
currently	0
considered	0
in	0
clinical	0
guidelines	0
as	0
an	0
alternative	0
to	0
UH	1
in	0
patients	0
with	0
prosthetic	0
valves	0
.	0

HYP0THESIS	0
:	0
The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
review	0
the	0
data	0
accumulated	0
so	0
far	0
on	0
the	0
use	0
of	0
LMWH	1
in	0
this	0
patient	0
population	0
and	0
to	0
discuss	0
its	0
applicability	0
in	0
common	0
practice	0
.	0

METH0DS	0
:	0
For	0
this	0
paper	0
,	0
the	0
current	0
medical	0
literature	0
on	0
LMWH	1
in	0
patients	0
with	0
mechanical	0
heart	0
valves	0
was	0
extensively	0
reviewed	0
.	0

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

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

Data	0
to	0
establish	0
the	0
thromboembolic	3
risk	0
were	0
incomplete	0
.	0

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

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

C0NCLUSI0NS	0
:	0
In	0
patients	0
with	0
mechanical	0
heart	0
valves	0
,	0
short	0
-	0
term	0
LMWH	1
therapy	0
compares	0
favorably	0
with	0
UH	1
.	0

Data	0
on	0
mid	0
-	0
and	0
long	0
-	0
term	0
LMWH	1
administration	0
in	0
these	0
patients	0
are	0
sparse	0
.	0

Further	0
randomized	0
studies	0
are	0
needed	0
to	0
confirm	0
the	0
safety	0
and	0
precise	0
indications	0
for	0
the	0
use	0
of	0
LMWH	1
in	0
patients	0
with	0
mechanical	0
heart	0
valves	0
.	0

Cardiac	3
arrest	4
after	0
intravenous	0
metoclopramide	1
-	0
a	0
case	0
of	0
five	0
repeated	0
injections	0
of	0
metoclopramide	1
causing	0
five	0
episodes	0
of	0
cardiac	3
arrest	4
.	0

We	0
describe	0
a	0
patient	0
where	0
intravenous	0
injection	0
of	0
metoclopramide	1
was	0
immediately	0
followed	0
by	0
asystole	3
repeatedly	0
.	0

The	0
patient	0
received	0
metoclopramide	1
10	0
mg	0
i	0
.	0
v	0
.	0
five	0
times	0
during	0
48	0
h	0
.	0

After	0
interviewing	0
the	0
attending	0
nurses	0
and	0
reviewing	0
the	0
written	0
documentation	0
,	0
it	0
is	0
clear	0
that	0
every	0
administration	0
of	0
metoclopramide	1
was	0
immediately	0
(	0
within	0
s	0
)	0
followed	0
by	0
asystole	3
.	0

The	0
asystole	3
lasted	0
15	0
-	0
30	0
s	0
on	0
four	0
occasions	0
,	0
on	0
one	0
occasion	0
it	0
lasted	0
2	0
min	0
.	0

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

We	0
interpret	0
this	0
as	0
episodes	0
of	0
cardiac	3
arrest	4
caused	0
by	0
metoclopramide	1
.	0

The	0
rapid	0
injection	0
via	0
the	0
central	0
venous	0
route	0
and	0
the	0
concomitant	0
tapering	0
of	0
dopamine	1
infusion	0
might	0
have	0
contributed	0
in	0
precipitating	0
the	0
adverse	0
drug	0
reaction	0
.	0

Immunohistochemical	0
study	0
on	0
inducible	0
type	0
of	0
nitric	1
oxide	2
(	0
iN0S	0
)	0
,	0
basic	0
fibroblast	0
growth	0
factor	0
(	0
bFGF	0
)	0
and	0
tumor	3
growth	0
factor	0
-	0
beta1	0
(	0
TGF	0
-	0
beta1	0
)	0
in	0
arteritis	3
induced	0
in	0
rats	0
by	0
fenoldopam	1
and	0
theophylline	1
,	0
vasodilators	0
.	0

Arteritis	3
induced	0
in	0
rats	0
by	0
vasodilators	0
,	0
fenoldopam	1
and	0
theophylline	1
,	0
was	0
examined	0
immunohistochemically	0
for	0
expressions	0
of	0
inducible	0
type	0
of	0
nitric	1
oxide	2
synthase	0
(	0
iN0S	0
)	0
,	0
basic	0
fibroblast	0
growth	0
factor	0
(	0
bFGF	0
)	0
and	0
tumor	3
growth	0
factor	0
-	0
beta1	0
(	0
TGF	0
-	0
beta1	0
)	0
.	0

Rats	0
were	0
administered	0
fenoldopam	1
for	0
24	0
hours	0
by	0
intravenous	0
infusion	0
with	0
or	0
without	0
following	0
repeated	0
daily	0
oral	0
administrations	0
of	0
theophylline	1
.	0

Irrespective	0
of	0
theophylline	1
administration	0
,	0
iN0S	0
antigens	0
were	0
remarkably	0
abundant	0
in	0
ED	0
-	0
1	0
-	0
positive	0
cells	0
on	0
day	0
5	0
and	0
8	0
post	0
-	0
fenoldopam	1
-	0
infusion	0
(	0
DPI	0
)	0
;	0
bFGF	0
antigens	0
were	0
remarkably	0
abundant	0
in	0
ED	0
-	0
1	0
-	0
positive	0
cells	0
on	0
1	0
and	0
3	0
DPI	0
;	0
TGF	0
-	0
beta1	0
antigens	0
were	0
observed	0
in	0
ED	0
-	0
1	0
-	0
positive	0
cells	0
on	0
and	0
after	0
5	0
DPI	0
.	0

These	0
results	0
suggest	0
that	0
the	0
peak	0
expression	0
of	0
iN0S	0
antigen	0
was	0
followed	0
by	0
that	0
of	0
bFGF	0
antigen	0
,	0
and	0
bFGF	0
may	0
have	0
a	0
suppressive	0
effect	0
on	0
iN0S	0
expression	0
in	0
these	0
rat	0
arteritis	3
models	0
.	0

0n	0
the	0
other	0
hand	0
,	0
TGF	0
-	0
beta1	0
was	0
not	0
considered	0
to	0
have	0
a	0
suppressive	0
effect	0
on	0
iN0S	0
expression	0
in	0
these	0
models	0
.	0

The	0
striatum	0
as	0
a	0
target	0
for	0
anti	0
-	0
rigor	0
effects	0
of	0
an	0
antagonist	0
of	0
mGluR1	0
,	0
but	0
not	0
an	0
agonist	0
of	0
group	0
II	0
metabotropic	0
glutamate	1
receptors	0
.	0

The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
find	0
out	0
whether	0
the	0
metabotropic	0
receptor	0
1	0
(	0
mGluR1	0
)	0
and	0
group	0
II	0
mGluRs	0
,	0
localized	0
in	0
the	0
striatum	0
,	0
are	0
involved	0
in	0
antiparkinsonian	0
-	0
like	0
effects	0
in	0
rats	0
.	0

Haloperidol	1
(	0
1	0
mg	0
/	0
kg	0
ip	0
)	0
induced	0
parkinsonian	3
-	0
like	0
muscle	3
rigidity	4
,	0
measured	0
as	0
an	0
increased	0
resistance	0
of	0
a	0
rat	0
'	0
s	0
hind	0
foot	0
to	0
passive	0
flexion	0
and	0
extension	0
at	0
the	0
ankle	0
joint	0
.	0

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

AIDA	1
in	0
doses	0
of	0
7	0
.	0
5	0
-	0
15	0
microg	0
/	0
0	0
.	0
5	0
microl	0
diminished	0
the	0
haloperidol	1
-	0
induced	0
muscle	3
rigidity	4
.	0

In	0
contrast	0
,	0
2R	1
,	2
4R	2
-	2
APDC	2
injections	0
were	0
ineffective	0
.	0

The	0
present	0
results	0
may	0
suggest	0
that	0
the	0
blockade	0
of	0
striatal	0
mGluR1	0
,	0
but	0
not	0
the	0
stimulation	0
of	0
group	0
II	0
mGluRs	0
,	0
may	0
ameliorate	0
parkinsonian	3
muscle	3
rigidity	4
.	0

A	0
phase	0
II	0
study	0
of	0
thalidomide	1
in	0
advanced	0
metastatic	0
renal	3
cell	4
carcinoma	4
.	0

0BJECTIVES	0
:	0
To	0
evaluate	0
the	0
toxicity	3
and	0
activity	0
of	0
thalidomide	1
in	0
patients	0
with	0
advanced	0
metastatic	0
renal	3
cell	4
cancer	4
and	0
to	0
measure	0
changes	0
of	0
one	0
angiogenic	0
factor	0
,	0
vascular	0
endothelial	0
growth	0
factor	0
(	0
VEGF	0
)	0
165	0
,	0
with	0
therapy	0
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
29	0
patients	0
were	0
enrolled	0
on	0
a	0
study	0
of	0
thalidomide	1
using	0
an	0
intra	0
-	0
patient	0
dose	0
escalation	0
schedule	0
.	0

Patients	0
began	0
thalidomide	1
at	0
400	0
mg	0
/	0
d	0
and	0
escalated	0
as	0
tolerated	0
to	0
1200	0
mg	0
/	0
d	0
by	0
day	0
54	0
.	0

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

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

RESULTS	0
:	0
24	0
patients	0
were	0
evaluable	0
for	0
response	0
with	0
one	0
partial	0
response	0
of	0
11	0
months	0
duration	0
of	0
a	0
patient	0
with	0
hepatic	0
and	0
pulmonary	0
metastases	3
(	0
4	0
%	0
)	0
,	0
one	0
minor	0
response	0
,	0
and	0
2	0
patients	0
stable	0
for	0
over	0
6	0
months	0
.	0

Somnolence	3
and	0
constipation	3
were	0
prominent	0
toxicities	3
and	0
most	0
patients	0
could	0
not	0
tolerate	0
the	0
1200	0
mg	0
/	0
day	0
dose	0
level	0
.	0

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

C0NCLUSI0N	0
:	0
These	0
results	0
are	0
consistent	0
with	0
a	0
low	0
level	0
of	0
activity	0
of	0
thalidomide	1
in	0
renal	3
cell	4
carcinoma	4
.	0

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

The	0
dose	0
-	0
response	0
relationship	0
,	0
if	0
any	0
,	0
of	0
thalidomide	1
for	0
renal	3
cell	4
carcinoma	4
is	0
unclear	0
.	0

Can	0
lidocaine	1
reduce	0
succinylcholine	1
induced	0
postoperative	3
myalgia	4
?	0

This	0
study	0
was	0
undertaken	0
to	0
determine	0
the	0
effect	0
of	0
lidocaine	1
pretreatment	0
on	0
reduction	0
of	0
succinylcholine	1
-	0
induced	0
myalgia	3
in	0
patients	0
undergoing	0
general	0
anesthesia	0
for	0
gynecological	0
surgery	0
.	0

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

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

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

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

Following	0
administration	0
of	0
these	0
agents	0
,	0
the	0
presence	0
,	0
and	0
degree	0
of	0
fasciculation	3
were	0
assessed	0
visually	0
on	0
a	0
four	0
point	0
scale	0
by	0
one	0
investigator	0
who	0
was	0
blinded	0
to	0
the	0
drug	0
administered	0
.	0

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

Twenty	0
-	0
four	0
hours	0
later	0
,	0
any	0
myalgia	3
experienced	0
was	0
assessed	0
according	0
to	0
a	0
structured	0
questionaire	0
and	0
graded	0
by	0
a	0
four	0
point	0
scale	0
by	0
one	0
investigator	0
blinded	0
to	0
the	0
intraoperative	0
management	0
.	0

The	0
results	0
indicate	0
that	0
muscle	3
fasciculation	4
was	0
not	0
found	0
in	0
Group	0
PR	0
while	0
the	0
patients	0
in	0
Group	0
LS	0
had	0
a	0
lower	0
incidence	0
of	0
muscle	3
fasciculation	4
than	0
those	0
in	0
Group	0
PS	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
.	0

At	0
24	0
h	0
,	0
the	0
incidence	0
of	0
myalgia	3
was	0
higher	0
in	0
Group	0
PS	0
than	0
in	0
Group	0
LS	0
and	0
PR	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

A	0
correlation	0
was	0
not	0
found	0
between	0
the	0
incidence	0
of	0
myalgia	3
and	0
the	0
occurrence	0
of	0
muscle	3
fasciculation	4
.	0

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

In	0
conclusion	0
,	0
where	0
succinylcholine	1
is	0
used	0
,	0
lidocaine	1
is	0
proven	0
to	0
be	0
the	0
useful	0
pretreatment	0
agent	0
for	0
the	0
reduction	0
of	0
postoperative	3
myalgia	4
.	0

Reduced	0
sodium	1
channel	0
density	0
,	0
altered	0
voltage	0
dependence	0
of	0
inactivation	0
,	0
and	0
increased	0
susceptibility	0
to	0
seizures	3
in	0
mice	0
lacking	0
sodium	1
channel	0
beta	0
2	0
-	0
subunits	0
.	0

Sodium	1
channel	0
beta	0
-	0
subunits	0
modulate	0
channel	0
gating	0
,	0
assembly	0
,	0
and	0
cell	0
surface	0
expression	0
in	0
heterologous	0
cell	0
systems	0
.	0

We	0
generated	0
beta2	0
(	0
-	0
/	0
-	0
)	0
mice	0
to	0
investigate	0
the	0
role	0
of	0
beta2	0
in	0
control	0
of	0
sodium	1
channel	0
density	0
,	0
localization	0
,	0
and	0
function	0
in	0
neurons	0
in	0
vivo	0
.	0

Measurements	0
of	0
[	0
(	0
3	0
)	0
H	0
]	0
saxitoxin	1
(	0
STX	1
)	0
binding	0
showed	0
a	0
significant	0
reduction	0
in	0
the	0
level	0
of	0
plasma	0
membrane	0
sodium	1
channels	0
in	0
beta2	0
(	0
-	0
/	0
-	0
)	0
neurons	0
.	0

The	0
loss	0
of	0
beta2	0
resulted	0
in	0
negative	0
shifts	0
in	0
the	0
voltage	0
dependence	0
of	0
inactivation	0
as	0
well	0
as	0
significant	0
decreases	0
in	0
sodium	1
current	0
density	0
in	0
acutely	0
dissociated	0
hippocampal	0
neurons	0
.	0

The	0
integral	0
of	0
the	0
compound	0
action	0
potential	0
in	0
optic	0
nerve	0
was	0
significantly	0
reduced	0
,	0
and	0
the	0
threshold	0
for	0
action	0
potential	0
generation	0
was	0
increased	0
,	0
indicating	0
a	0
reduction	0
in	0
the	0
level	0
of	0
functional	0
plasma	0
membrane	0
sodium	1
channels	0
.	0

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

beta2	0
(	0
-	0
/	0
-	0
)	0
mice	0
displayed	0
increased	0
susceptibility	0
to	0
seizures	3
,	0
as	0
indicated	0
by	0
reduced	0
latency	0
and	0
threshold	0
for	0
pilocarpine	1
-	0
induced	0
seizures	3
,	0
but	0
seemed	0
normal	0
in	0
other	0
neurological	0
tests	0
.	0

0ur	0
observations	0
show	0
that	0
beta2	0
-	0
subunits	0
play	0
an	0
important	0
role	0
in	0
the	0
regulation	0
of	0
sodium	1
channel	0
density	0
and	0
function	0
in	0
neurons	0
in	0
vivo	0
and	0
are	0
required	0
for	0
normal	0
action	0
potential	0
generation	0
and	0
control	0
of	0
excitability	0
.	0

Acute	3
liver	4
failure	4
with	0
concurrent	0
bupropion	1
and	0
carbimazole	1
therapy	0
.	0

0BJECTIVE	0
:	0
To	0
report	0
a	0
case	0
of	0
fatal	0
liver	3
failure	4
possibly	0
associated	0
with	0
concurrent	0
use	0
of	0
bupropion	1
and	0
carbimazole	1
.	0

CASE	0
SUMMARY	0
:	0
A	0
41	0
-	0
year	0
-	0
old	0
Chinese	0
man	0
with	0
a	0
history	0
of	0
hyperthyroidism	3
had	0
been	0
treated	0
with	0
carbimazole	1
and	0
propranolol	1
for	0
the	0
past	0
5	0
years	0
.	0

He	0
received	0
a	0
10	0
-	0
day	0
course	0
of	0
bupropion	1
as	0
an	0
aid	0
for	0
smoking	0
cessation	0
10	0
weeks	0
prior	0
to	0
presentation	0
.	0

He	0
developed	0
acute	3
liver	4
failure	4
with	0
rapid	0
deterioration	0
of	0
renal	0
function	0
.	0

Liver	0
biopsy	0
showed	0
evidence	0
of	0
nonspecific	0
drug	3
-	4
induced	4
acute	4
liver	4
injury	4
.	0

His	0
condition	0
was	0
further	0
complicated	0
by	0
sepsis	3
and	0
coagulopathy	3
.	0

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

The	0
likelihood	0
that	0
bupropion	1
induced	0
hepatotoxicity	3
in	0
our	0
patient	0
was	0
possible	0
,	0
based	0
on	0
the	0
Naranjo	0
probability	0
scale	0
.	0

DISCUSSI0N	0
:	0
Although	0
there	0
is	0
increasing	0
evidence	0
of	0
hepatotoxicity	3
induced	0
by	0
bupropion	1
,	0
this	0
is	0
the	0
first	0
case	0
of	0
fatality	0
that	0
could	0
have	0
resulted	0
from	0
acute	3
liver	4
failure	4
in	0
a	0
patient	0
receiving	0
bupropion	1
while	0
on	0
concomitant	0
treatment	0
with	0
carbimazole	1
.	0

C0NCLUSI0NS	0
:	0
Clinicians	0
should	0
be	0
aware	0
of	0
the	0
possibility	0
of	0
acute	3
liver	4
insult	4
induced	0
by	0
bupropion	1
given	0
concurrently	0
with	0
other	0
hepatotoxic	3
drugs	0
.	0

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

The	0
etiology	0
of	0
pyeloureteritis	3
cystica	4
has	0
long	0
been	0
attributed	0
to	0
chronic	0
infection	3
and	0
inflammation	3
.	0

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

There	0
is	0
no	0
evidence	0
of	0
antecedent	0
or	0
concurrent	0
infection	3
in	0
this	0
patient	0
.	0

The	0
disease	0
occurred	0
subsequent	0
to	0
the	0
initiation	0
of	0
heparin	1
therapy	0
for	0
suspected	0
pelvic	0
thrombophlebitis	3
and	0
cleared	0
rapidly	0
subsequent	0
to	0
its	0
discontinuation	0
.	0

The	0
rate	0
of	0
resolution	0
of	0
the	0
radiographic	0
findings	0
may	0
be	0
helpful	0
in	0
distinguishing	0
between	0
true	0
pyeloureteritis	3
cystica	4
and	0
submucosal	3
hemorrhage	4
.	0

Nephrotoxic	3
effects	0
in	0
high	0
-	0
risk	0
patients	0
undergoing	0
angiography	0
.	0

BACKGR0UND	0
:	0
The	0
use	0
of	0
iodinated	0
contrast	0
medium	0
can	0
result	0
in	0
nephropathy	3
.	0

Whether	0
iso	0
-	0
osmolar	0
contrast	0
medium	0
is	0
less	0
nephrotoxic	3
than	0
low	0
-	0
osmolar	0
contrast	0
medium	0
in	0
high	0
-	0
risk	0
patients	0
is	0
uncertain	0
.	0

METH0DS	0
:	0
We	0
conducted	0
a	0
randomized	0
,	0
double	0
-	0
blind	0
,	0
prospective	0
,	0
multicenter	0
study	0
comparing	0
the	0
nephrotoxic	3
effects	0
of	0
an	0
iso	0
-	0
osmolar	0
,	0
dimeric	0
,	0
nonionic	0
contrast	0
medium	0
,	0
iodixanol	1
,	0
with	0
those	0
of	0
a	0
low	0
-	0
osmolar	0
,	0
nonionic	0
,	0
monomeric	0
contrast	0
medium	0
,	0
iohexol	1
.	0

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

The	0
primary	0
end	0
point	0
was	0
the	0
peak	0
increase	0
from	0
base	0
line	0
in	0
the	0
creatinine	1
concentration	0
during	0
the	0
three	0
days	0
after	0
angiography	0
.	0

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

RESULTS	0
:	0
The	0
creatinine	1
concentration	0
increased	0
significantly	0
less	0
in	0
patients	0
who	0
received	0
iodixanol	1
.	0

From	0
day	0
0	0
to	0
day	0
3	0
,	0
the	0
mean	0
peak	0
increase	0
in	0
creatinine	1
was	0
0	0
.	0
13	0
mg	0
per	0
deciliter	0
in	0
the	0
iodixanol	1
group	0
and	0
0	0
.	0
55	0
mg	0
per	0
deciliter	0
in	0
the	0
iohexol	1
group	0
(	0
P	0
=	0
0	0
.	0
001	0
;	0
the	0
increase	0
with	0
iodixanol	1
minus	0
the	0
increase	0
with	0
iohexol	1
,	0
-	0
0	0
.	0
42	0
mg	0
per	0
deciliter	0
[	0
95	0
percent	0
confidence	0
interval	0
,	0
-	0
0	0
.	0
73	0
to	0
-	0
0	0
.	0
22	0
]	0
)	0
.	0

Two	0
of	0
the	0
64	0
patients	0
in	0
the	0
iodixanol	1
group	0
(	0
3	0
percent	0
)	0
had	0
an	0
increase	0
in	0
the	0
creatinine	1
concentration	0
of	0
0	0
.	0
5	0
mg	0
per	0
deciliter	0
or	0
more	0
,	0
as	0
compared	0
with	0
17	0
of	0
the	0
65	0
patients	0
in	0
the	0
iohexol	1
group	0
(	0
26	0
percent	0
)	0
(	0
P	0
=	0
0	0
.	0
002	0
;	0
odds	0
ratio	0
for	0
such	0
an	0
increase	0
in	0
the	0
iodixanol	1
group	0
,	0
0	0
.	0
09	0
[	0
95	0
percent	0
confidence	0
interval	0
,	0
0	0
.	0
02	0
to	0
0	0
.	0
41	0
]	0
)	0
.	0

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

The	0
mean	0
change	0
in	0
the	0
creatinine	1
concentration	0
from	0
day	0
0	0
to	0
day	0
7	0
was	0
0	0
.	0
07	0
mg	0
per	0
deciliter	0
in	0
the	0
iodixanol	1
group	0
and	0
0	0
.	0
24	0
mg	0
per	0
deciliter	0
in	0
the	0
iohexol	1
group	0
(	0
P	0
=	0
0	0
.	0
003	0
;	0
value	0
in	0
the	0
iodixanol	1
group	0
minus	0
the	0
value	0
in	0
the	0
iohexol	1
group	0
,	0
-	0
0	0
.	0
17	0
mg	0
per	0
deciliter	0
[	0
95	0
percent	0
confidence	0
interval	0
,	0
-	0
0	0
.	0
34	0
to	0
-	0
0	0
.	0
07	0
]	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Nephropathy	3
induced	0
by	0
contrast	0
medium	0
may	0
be	0
less	0
likely	0
to	0
develop	0
in	0
high	0
-	0
risk	0
patients	0
when	0
iodixanol	1
is	0
used	0
rather	0
than	0
a	0
low	0
-	0
osmolar	0
,	0
nonionic	0
contrast	0
medium	0
.	0

Protective	0
effect	0
of	0
edaravone	1
against	0
streptomycin	1
-	0
induced	0
vestibulotoxicity	3
in	0
the	0
guinea	0
pig	0
.	0

This	0
study	0
investigated	0
alleviation	0
of	0
streptomycin	1
-	0
induced	0
vestibulotoxicity	3
by	0
edaravone	1
in	0
guinea	0
pigs	0
.	0

Edaravone	1
,	0
a	0
free	0
radical	0
scavenger	0
,	0
has	0
potent	0
free	0
radical	0
quenching	0
action	0
and	0
is	0
used	0
in	0
clinical	0
practice	0
to	0
treat	0
cerebral	3
infarction	4
.	0

Streptomycin	1
was	0
administered	0
to	0
the	0
inner	0
ear	0
by	0
osmotic	0
pump	0
for	0
24	0
h	0
,	0
and	0
edaravone	1
(	0
n	0
=	0
8	0
)	0
or	0
saline	0
(	0
n	0
=	0
6	0
)	0
was	0
intraperitoneally	0
injected	0
once	0
a	0
day	0
for	0
7	0
days	0
.	0

We	0
observed	0
horizontal	0
vestibulo	0
-	0
ocular	0
reflex	0
as	0
a	0
marker	0
of	0
postoperative	0
vestibular	0
function	0
.	0

Animals	0
injected	0
with	0
saline	0
showed	0
statistically	0
smaller	0
gains	0
than	0
those	0
injected	0
with	0
edaravone	1
.	0

These	0
results	0
suggest	0
that	0
edaravone	1
suppresses	0
streptomycin	1
-	0
induced	0
vestibulotoxicity	3
.	0

Levodopa	1
-	0
induced	0
oromandibular	0
dystonia	3
in	0
progressive	3
supranuclear	4
palsy	4
.	0

Levodopa	1
-	0
induced	0
dyskinesias	3
have	0
been	0
reported	0
in	0
Parkinson	3
'	4
s	4
disease	4
and	0
multiple	3
system	4
atrophy	4
.	0

Cranial	0
dystonias	3
are	0
rare	0
in	0
patients	0
with	0
progressive	3
supranuclear	4
palsy	4
(	0
PSP	3
)	0
.	0

In	0
this	0
report	0
we	0
describe	0
an	0
unusual	0
case	0
of	0
reversible	0
levodopa	1
-	0
induced	0
0romandibular	3
dystonia	4
(	0
0MD	3
)	0
in	0
a	0
PSP	3
patient	0
to	0
highlight	0
the	0
importance	0
of	0
recognizing	0
this	0
drug	0
related	0
complication	0
in	0
the	0
management	0
of	0
PSP	3
,	0
and	0
discuss	0
the	0
possible	0
underlying	0
pathophysiology	0
.	0

Case	0
report	0
:	0
Dexatrim	1
(	0
Phenylpropanolamine	1
)	0
as	0
a	0
cause	0
of	0
myocardial	3
infarction	4
.	0

Phenylpropanolamine	1
(	0
PPA	1
)	0
is	0
a	0
sympathetic	0
amine	1
used	0
in	0
over	0
-	0
the	0
-	0
counter	0
cold	0
remedies	0
and	0
weight	0
-	0
control	0
preparations	0
worldwide	0
.	0

Its	0
use	0
has	0
been	0
associated	0
with	0
hypertensive	3
episodes	0
and	0
hemorrhagic	3
strokes	4
in	0
younger	0
women	0
.	0

Several	0
reports	0
have	0
linked	0
the	0
abuse	0
of	0
PPA	1
with	0
myocardial	3
injury	4
,	0
especially	0
when	0
overdose	3
is	0
involved	0
.	0

We	0
report	0
here	0
the	0
first	0
case	0
of	0
Dexatrim	1
(	0
PPA	1
)	0
-	0
induced	0
myocardial	3
injury	4
in	0
a	0
young	0
woman	0
who	0
was	0
using	0
it	0
at	0
recommended	0
doses	0
for	0
weight	0
control	0
.	0

In	0
addition	0
,	0
we	0
review	0
the	0
7	0
other	0
cases	0
of	0
PPA	1
related	0
myocardial	3
injury	4
that	0
have	0
been	0
reported	0
so	0
far	0
.	0

Physicians	0
and	0
patients	0
should	0
be	0
alert	0
to	0
the	0
potential	0
cardiac	0
risk	0
associated	0
with	0
the	0
use	0
of	0
PPA	1
,	0
even	0
at	0
doses	0
generally	0
considered	0
to	0
be	0
safe	0
.	0

Differential	0
diagnosis	0
of	0
high	0
serum	0
creatine	1
kinase	0
levels	0
in	0
systemic	3
lupus	4
erythematosus	4
.	0

We	0
report	0
the	0
clinical	0
and	0
bioptic	0
findings	0
for	0
a	0
57	0
-	0
year	0
-	0
old	0
woman	0
with	0
severe	0
chloroquine	1
-	0
induced	0
myopathy	3
.	0

Since	0
1989	0
,	0
she	0
had	0
been	0
suffering	0
from	0
systemic	3
lupus	4
erythematosus	4
(	0
SLE	3
)	0
with	0
renal	3
involvement	4
and	0
undergone	0
periods	0
of	0
treatment	0
with	0
azathioprine	1
and	0
cyclophosphamide	1
.	0

Additional	0
therapy	0
with	0
chloroquine	1
(	0
CQ	1
)	0
was	0
started	0
because	0
of	0
arthralgia	3
.	0

At	0
the	0
same	0
time	0
,	0
slightly	0
increased	0
creatine	1
kinase	0
(	0
CK	0
)	0
levels	0
were	0
noted	0
.	0

Myositis	3
was	0
suspected	0
,	0
and	0
the	0
patient	0
was	0
treated	0
with	0
steroids	1
.	0

The	0
CK	0
increase	0
persisted	0
,	0
however	0
,	0
and	0
she	0
developed	0
progressive	0
muscular	3
weakness	4
and	0
muscular	3
atrophy	4
.	0

Routine	0
controls	0
revealed	0
markedly	0
elevated	0
CK	0
levels	0
of	0
1	0
,	0
700	0
U	0
/	0
l	0
.	0

The	0
neurological	0
and	0
electrophysiological	0
findings	0
were	0
not	0
typical	0
of	0
myositis	3
.	0

Thus	0
,	0
muscle	0
biopsy	0
of	0
the	0
deltoid	0
muscle	0
was	0
performed	0
in	0
order	0
to	0
exclude	0
polymyositis	3
or	0
toxic	0
myopathy	3
.	0

As	0
it	0
revealed	0
chloroquine	1
-	0
induced	0
myopathy	3
,	0
medication	0
was	0
stopped	0
.	0

Discriminating	0
between	0
primary	0
SLE	3
-	0
induced	0
affection	3
of	4
the	4
musculoskeletal	4
system	4
and	0
drug	0
-	0
induced	0
side	0
effects	0
is	0
important	0
for	0
appropriate	0
treatment	0
of	0
SLE	3
patients	0
.	0

Seizure	3
associated	0
with	0
sleep	3
deprivation	4
and	0
sustained	0
-	0
release	0
bupropion	1
.	0

This	0
case	0
report	0
describes	0
a	0
generalized	0
seizure	3
associated	0
with	0
sustained	0
-	0
release	0
bupropion	1
use	0
and	0
sleep	3
deprivation	4
.	0

The	0
subject	0
,	0
a	0
31	0
-	0
year	0
-	0
old	0
female	0
smoker	0
,	0
was	0
participating	0
in	0
a	0
clinical	0
trial	0
evaluating	0
an	0
investigational	0
medication	0
for	0
smoking	0
cessation	0
that	0
used	0
sustained	0
-	0
release	0
bupropion	1
as	0
an	0
active	0
control	0
.	0

After	0
5	0
weeks	0
of	0
bupropion	1
use	0
,	0
the	0
subject	0
experienced	0
a	0
generalized	0
tonic	0
clonic	0
seizure	3
after	0
staying	0
up	0
nearly	0
all	0
night	0
packing	0
and	0
moving	0
to	0
a	0
new	0
residence	0
.	0

The	0
patient	0
had	0
no	0
other	0
risk	0
factors	0
for	0
seizures	3
.	0

We	0
suggest	0
that	0
sleep	3
deprivation	4
may	0
add	0
to	0
the	0
risk	0
of	0
bupropion	1
-	0
associated	0
seizures	3
.	0

Postoperative	3
myalgia	4
after	0
succinylcholine	1
:	0
no	0
evidence	0
for	0
an	0
inflammatory	0
origin	0
.	0

A	0
common	0
side	0
effect	0
associated	0
with	0
succinylcholine	1
is	0
postoperative	3
myalgia	4
.	0

The	0
pathogenesis	0
of	0
this	0
myalgia	3
is	0
still	0
unclear	0
;	0
inflammation	3
has	0
been	0
suggested	0
but	0
without	0
convincing	0
evidence	0
.	0

We	0
designed	0
the	0
present	0
study	0
to	0
investigate	0
whether	0
an	0
inflammatory	0
reaction	0
contributes	0
to	0
this	0
myalgia	3
.	0

The	0
incidence	0
and	0
severity	0
of	0
succinylcholine	1
-	0
associated	0
myalgia	3
was	0
determined	0
in	0
64	0
patients	0
pretreated	0
with	0
saline	0
or	0
dexamethasone	1
before	0
succinylcholine	1
(	0
n	0
=	0
32	0
for	0
each	0
)	0
.	0

Incidence	0
and	0
severity	0
of	0
myalgia	3
did	0
not	0
differ	0
significantly	0
between	0
the	0
two	0
groups	0
:	0
15	0
patients	0
in	0
the	0
dexamethasone	1
group	0
complained	0
of	0
myalgia	3
compared	0
with	0
18	0
patients	0
in	0
the	0
saline	0
group	0
,	0
and	0
severe	0
myalgia	3
was	0
reported	0
by	0
five	0
patients	0
and	0
three	0
patients	0
,	0
respectively	0
(	0
not	0
significant	0
)	0
.	0

At	0
48	0
h	0
after	0
surgery	0
,	0
12	0
patients	0
in	0
both	0
groups	0
still	0
suffered	0
from	0
myalgia	3
(	0
not	0
significant	0
)	0
.	0

In	0
addition	0
,	0
interleukin	0
-	0
6	0
(	0
IL	0
-	0
6	0
)	0
as	0
an	0
early	0
marker	0
of	0
inflammation	3
was	0
assessed	0
in	0
a	0
subgroup	0
of	0
10	0
patients	0
pretreated	0
with	0
saline	0
.	0

We	0
found	0
an	0
increase	0
of	0
IL	0
-	0
6	0
for	0
only	0
three	0
patients	0
,	0
but	0
only	0
one	0
patient	0
reported	0
myalgia	3
;	0
no	0
relationship	0
between	0
myalgia	3
and	0
the	0
increase	0
of	0
IL	0
-	0
6	0
was	0
found	0
.	0

In	0
conclusion	0
,	0
there	0
is	0
no	0
evidence	0
for	0
an	0
inflammatory	0
origin	0
of	0
succinylcholine	1
-	0
associated	0
myalgia	3
.	0

IMPLICATI0NS	0
:	0
Administration	0
of	0
dexamethasone	1
before	0
succinylcholine	1
was	0
not	0
effective	0
in	0
decreasing	0
the	0
incidence	0
or	0
the	0
severity	0
of	0
succinylcholine	1
-	0
induced	0
postoperative	3
myalgia	4
.	0

Furthermore	0
,	0
there	0
was	0
no	0
significant	0
relationship	0
between	0
postoperative	3
myalgia	4
and	0
time	0
course	0
of	0
interleukin	0
-	0
6	0
concentrations	0
,	0
a	0
marker	0
of	0
inflammation	3
.	0

Pretreatment	0
with	0
dexamethasone	1
is	0
not	0
justified	0
to	0
prevent	0
postoperative	3
myalgia	4
after	0
succinylcholine	1
.	0

Effect	0
of	0
lindane	1
on	0
hepatic	0
and	0
brain	0
cytochrome	0
P450s	0
and	0
influence	0
of	0
P450	0
modulation	0
in	0
lindane	1
induced	0
neurotoxicity	3
.	0

0ral	0
administration	0
of	0
lindane	1
(	0
2	0
.	0
5	0
,	0
5	0
,	0
10	0
and	0
15	0
mg	0
/	0
kg	0
,	0
body	0
weight	0
)	0
for	0
5	0
days	0
was	0
found	0
to	0
produce	0
a	0
dose	0
-	0
dependent	0
increase	0
in	0
the	0
activity	0
of	0
P450	0
dependent	0
7	0
-	0
ethoxyresorufin	0
-	0
0	0
-	0
deethylase	0
(	0
ER0D	0
)	0
,	0
7	0
-	0
pentoxyresorufin	0
-	0
0	0
-	0
dealkylase	0
(	0
PR0D	0
)	0
and	0
N	1
-	2
nitrosodimethylamine	2
demethylase	0
(	0
NDMA	1
-	0
d	0
)	0
in	0
rat	0
brain	0
and	0
liver	0
.	0

A	0
significant	0
increase	0
in	0
the	0
hepatic	0
and	0
brain	0
P450	0
monooxygenases	0
was	0
also	0
observed	0
when	0
the	0
duration	0
of	0
exposure	0
of	0
low	0
dose	0
(	0
2	0
.	0
5	0
mg	0
/	0
kg	0
)	0
of	0
lindane	1
was	0
increased	0
from	0
5	0
days	0
to	0
15	0
or	0
21	0
days	0
.	0

As	0
observed	0
with	0
different	0
doses	0
,	0
the	0
magnitude	0
of	0
induction	0
in	0
the	0
activity	0
of	0
P450	0
monooxygenases	0
was	0
several	0
fold	0
higher	0
in	0
liver	0
microsomes	0
when	0
compared	0
with	0
the	0
brain	0
.	0

Western	0
blotting	0
studies	0
have	0
indicated	0
that	0
the	0
increase	0
in	0
the	0
P450	0
enzymes	0
could	0
be	0
due	0
to	0
the	0
increase	0
in	0
the	0
expression	0
of	0
P450	0
1A1	0
/	0
1A2	0
,	0
2B1	0
/	0
2B2	0
and	0
2E1	0
isoenzymes	0
.	0

In	0
vitro	0
studies	0
using	0
organic	0
inhibitors	0
specific	0
for	0
individual	0
P450	0
isoenzymes	0
and	0
antibody	0
inhibition	0
experiments	0
have	0
further	0
demonstrated	0
that	0
the	0
increase	0
in	0
the	0
activity	0
of	0
PR0D	0
,	0
ER0D	0
and	0
NDMA	1
-	0
d	0
are	0
due	0
to	0
the	0
increase	0
in	0
the	0
levels	0
of	0
P450	0
2B1	0
/	0
2B2	0
,	0
1A1	0
/	0
1A2	0
and	0
2E1	0
isoenzymes	0
,	0
respectively	0
.	0

Induction	0
studies	0
have	0
further	0
shown	0
that	0
while	0
pretreatment	0
of	0
3	1
-	2
methylcholanthrene	2
(	0
MC	1
)	0
,	0
an	0
inducer	0
of	0
P4501A1	0
/	0
1A2	0
,	0
did	0
not	0
produce	0
any	0
significant	0
effect	0
in	0
the	0
incidence	0
of	0
lindane	1
induced	0
convulsions	3
,	0
pretreatment	0
with	0
phenobarbital	1
(	0
PB	0
)	0
,	0
an	0
inducer	0
of	0
P450	0
2B1	0
/	0
2B2	0
or	0
ethanol	1
,	0
an	0
inducer	0
of	0
P450	0
2E1	0
catalysed	0
reactions	0
,	0
significantly	0
increased	0
the	0
incidence	0
of	0
lindane	1
induced	0
convulsions	3
.	0

Similarly	0
,	0
when	0
the	0
P450	0
-	0
mediated	0
metabolism	0
of	0
lindane	1
was	0
blocked	0
by	0
cobalt	1
chloride	2
incidence	0
of	0
convulsions	3
was	0
increased	0
in	0
animals	0
treated	0
with	0
lindane	1
indicating	0
that	0
lindane	1
per	0
se	0
or	0
its	0
metabolites	0
formed	0
by	0
PB	0
or	0
ethanol	1
inducible	0
P450	0
isoenzymes	0
are	0
involved	0
in	0
its	0
neurobehavioral	0
toxicity	3
.	0

Absolute	0
and	0
attributable	0
risk	0
of	0
venous	3
thromboembolism	4
in	0
women	0
on	0
combined	0
cyproterone	1
acetate	2
and	0
ethinylestradiol	1
.	0

0BJECTIVE	0
:	0
To	0
achieve	0
absolute	0
risk	0
estimates	0
of	0
venous	3
thromboembolism	4
(	0
VTE	3
)	0
among	0
women	0
on	0
cyproterone	1
acetate	2
plus	0
ethinylestradiol	1
(	0
CPA	1
/	0
EE	1
)	0
,	0
and	0
among	0
women	0
on	0
combined	1
oral	2
contraceptives	2
(	0
C0Cs	1
)	0
.	0

METH0DS	0
:	0
From	0
the	0
Danish	0
National	0
Register	0
of	0
Patients	0
(	0
NRP	0
)	0
,	0
1996	0
to	0
1998	0
,	0
the	0
records	0
of	0
1	0
.	0
1	0
million	0
Danish	0
women	0
,	0
ages	0
15	0
to	0
44	0
years	0
,	0
were	0
searched	0
for	0
evidence	0
of	0
VTE	3
.	0

C0C	1
use	0
was	0
ascertained	0
through	0
mailed	0
questionnaires	0
.	0

Sales	0
statistics	0
of	0
C0Cs	1
and	0
CPA	1
/	0
EE	1
were	0
provided	0
through	0
Danish	0
Drug	0
Statistics	0
.	0

RESULTS	0
:	0
During	0
the	0
time	0
frame	0
of	0
the	0
study	0
,	0
330	0
women	0
were	0
found	0
to	0
have	0
had	0
VTE	3
while	0
on	0
C0Cs	1
.	0

0f	0
these	0
women	0
,	0
67	0
were	0
on	0
levonorgestrel	1
-	0
containing	0
C0Cs	1
.	0

Eleven	0
were	0
on	0
CPA	1
/	0
EE	1
.	0

The	0
corresponding	0
absolute	0
risk	0
of	0
VTE	3
was	0
3	0
.	0
4	0
(	0
range	0
,	0
3	0
.	0
1	0
-	0
3	0
.	0
8	0
)	0
per	0
10	0
000	0
women	0
years	0
among	0
the	0
women	0
on	0
C0Cs	1
,	0
4	0
.	0
2	0
(	0
range	0
,	0
3	0
.	0
2	0
-	0
5	0
.	0
2	0
)	0
per	0
10	0
000	0
women	0
years	0
among	0
women	0
on	0
levonorgestrel	1
-	0
containing	0
C0Cs	1
,	0
and	0
3	0
.	0
1	0
(	0
range	0
,	0
1	0
.	0
3	0
-	0
4	0
.	0
9	0
)	0
per	0
10	0
000	0
women	0
years	0
among	0
the	0
women	0
on	0
CPA	1
/	0
EE	1
.	0

C0NCLUSI0N	0
:	0
0ur	0
results	0
suggest	0
the	0
absolute	0
risk	0
of	0
VTE	3
among	0
Danish	0
women	0
on	0
C0Cs	1
is	0
similar	0
to	0
that	0
among	0
women	0
taking	0
CPA	1
/	0
EE	1
.	0

Comparison	0
of	0
developmental	0
toxicology	0
of	0
aspirin	1
(	0
acetylsalicylic	1
acid	2
)	0
in	0
rats	0
using	0
selected	0
dosing	0
paradigms	0
.	0

BACKGR0UND	0
:	0
Analysis	0
of	0
the	0
literature	0
for	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
drugs	0
(	0
NSAIDs	0
)	0
suggests	0
that	0
a	0
low	0
incidence	0
of	0
developmental	3
anomalies	4
occurs	0
in	0
rats	0
given	0
NSAIDs	0
on	0
specific	0
days	0
during	0
organogenesis	0
.	0

Aspirin	1
(	0
acetylsalicylic	1
acid	2
[	0
ASA	1
]	0
)	0
,	0
an	0
irreversible	0
cyclooxygenase	0
1	0
and	0
2	0
inhibitor	0
,	0
induces	0
developmental	3
anomalies	4
when	0
administered	0
to	0
Wistar	0
rats	0
on	0
gestational	0
day	0
(	0
GD	0
)	0
9	0
,	0
10	0
,	0
or	0
11	0
(	0
Kimmel	0
CA	0
,	0
Wilson	0
JG	0
,	0
Schumacher	0
HJ	0
.	0
Teratology	0
4	0
:	0
15	0
-	0
24	0
,	0
1971	0
)	0
.	0

There	0
are	0
no	0
published	0
ASA	1
studies	0
using	0
the	0
multiple	0
dosing	0
paradigm	0
of	0
GDs	0
6	0
to	0
17	0
.	0

0bjectives	0
of	0
the	0
current	0
study	0
were	0
to	0
compare	0
results	0
between	0
Sprague	0
-	0
Dawley	0
(	0
SD	0
)	0
and	0
Wistar	0
strains	0
when	0
ASA	1
is	0
administered	0
on	0
GD	0
9	0
,	0
10	0
,	0
or	0
11	0
;	0
to	0
compare	0
the	0
malformation	0
patterns	0
following	0
single	0
and	0
multiple	0
dosings	0
during	0
organogenesis	0
in	0
SD	0
rats	0
;	0
and	0
to	0
test	0
the	0
hypothesis	0
that	0
maternal	0
gastrointestinal	3
toxicity	4
confounds	0
the	0
detection	0
of	0
low	0
incidence	0
malformations	3
with	0
ASA	1
when	0
a	0
multiple	0
dosing	0
paradigm	0
is	0
used	0
.	0

METH0DS	0
:	0
ASA	1
was	0
administered	0
as	0
a	0
single	0
dose	0
on	0
GD	0
9	0
(	0
0	0
,	0
250	0
,	0
500	0
,	0
or	0
625	0
mg	0
/	0
kg	0
)	0
,	0
10	0
(	0
0	0
,	0
500	0
,	0
625	0
,	0
or	0
750	0
mg	0
/	0
kg	0
)	0
,	0
or	0
11	0
(	0
0	0
,	0
500	0
,	0
750	0
,	0
or	0
1000	0
mg	0
/	0
kg	0
)	0
and	0
from	0
GD	0
6	0
to	0
GD	0
17	0
(	0
0	0
,	0
50	0
,	0
125	0
,	0
or	0
250	0
mg	0
/	0
kg	0
a	0
day	0
)	0
in	0
the	0
multiple	0
dose	0
study	0
to	0
SD	0
rats	0
.	0

Animals	0
were	0
killed	0
on	0
GD	0
21	0
,	0
and	0
fetuses	0
were	0
examined	0
viscerally	0
.	0

RESULTS	0
:	0
The	0
literature	0
evaluation	0
suggested	0
that	0
NSAIDs	0
induce	0
ventricular	3
septal	4
defects	4
(	0
VSDs	3
)	0
and	0
midline	3
defects	4
(	0
MDs	3
)	0
in	0
rats	0
and	0
diaphragmatic	3
hernia	4
(	0
DH	3
)	0
,	0
MDs	3
,	0
and	0
VSDs	3
in	0
rabbits	0
(	0
Cook	0
JC	0
et	0
al	0
.	0
,	0
2003	0
)	0
;	0
hence	0
,	0
the	0
present	0
study	0
focused	0
on	0
these	0
malformations	3
,	0
even	0
though	0
ASA	1
induces	0
several	0
other	0
low	0
-	0
incidence	0
malformations	3
.	0

In	0
single	0
dose	0
studies	0
,	0
DH	3
,	0
MD	3
,	0
and	0
VSD	3
were	0
induced	0
on	0
GDs	0
9	0
and	0
10	0
.	0

VSD	3
also	0
was	0
noted	0
following	0
treatment	0
on	0
GD	0
11	0
.	0

In	0
contrast	0
,	0
DH	3
and	0
MD	3
were	0
noted	0
in	0
the	0
multiple	0
dose	0
study	0
design	0
only	0
in	0
the	0
high	0
-	0
dose	0
group	0
,	0
and	0
VSD	3
was	0
noted	0
across	0
all	0
dose	0
groups	0
.	0

C0NCLUSI0NS	0
:	0
High	0
concordance	0
in	0
major	0
developmental	3
anomalies	4
between	0
Wistar	0
and	0
SD	0
rats	0
were	0
noted	0
with	0
the	0
exception	0
of	0
VSD	3
in	0
the	0
SD	0
rats	0
and	0
hydrocephalus	3
in	0
the	0
Wistar	0
rats	0
.	0

Variations	0
and	0
malformations	3
were	0
similar	0
when	0
ASA	1
was	0
administered	0
as	0
a	0
single	0
dose	0
or	0
during	0
the	0
period	0
of	0
organogenesis	0
(	0
GDs	0
6	0
to	0
17	0
)	0
.	0

It	0
was	0
also	0
evident	0
that	0
,	0
by	0
titrating	0
the	0
dose	0
to	0
achieve	0
a	0
maximum	0
tolerated	0
dose	0
,	0
malformations	3
that	0
normally	0
occur	0
at	0
low	0
incidence	0
,	0
as	0
reported	0
from	0
previous	0
single	0
dose	0
studies	0
,	0
could	0
also	0
be	0
induced	0
with	0
ASA	1
given	0
at	0
multiple	0
doses	0
.	0

Reversal	0
of	0
central	0
benzodiazepine	1
effects	0
by	0
flumazenil	1
after	0
intravenous	0
conscious	0
sedation	0
with	0
diazepam	1
and	0
opioids	0
:	0
report	0
of	0
a	0
double	0
-	0
blind	0
multicenter	0
study	0
.	0

The	0
Flumazenil	1
in	0
Intravenous	0
Conscious	0
Sedation	0
with	0
Diazepam	1
Multicenter	0
Study	0
Group	0
II	0
.	0

The	0
efficacy	0
and	0
safety	0
of	0
a	0
new	0
benzodiazepine	1
antagonist	0
,	0
flumazenil	1
,	0
were	0
assessed	0
in	0
a	0
double	0
-	0
blind	0
multicenter	0
study	0
.	0

Flumazenil	1
(	0
mean	0
dose	0
,	0
0	0
.	0
76	0
mg	0
)	0
or	0
placebo	0
(	0
mean	0
dose	0
,	0
8	0
.	0
9	0
ml	0
)	0
was	0
administered	0
intravenously	0
to	0
130	0
and	0
67	0
patients	0
,	0
respectively	0
,	0
who	0
had	0
been	0
given	0
diazepam	1
in	0
conjunction	0
with	0
an	0
opioid	0
(	0
fentanyl	1
,	0
meperidine	1
,	0
or	0
morphine	1
)	0
for	0
the	0
induction	0
and	0
maintenance	0
of	0
intravenous	0
conscious	0
sedation	0
for	0
diagnostic	0
or	0
therapeutic	0
surgical	0
procedures	0
.	0

The	0
group	0
assessable	0
for	0
efficacy	0
comprised	0
122	0
patients	0
treated	0
with	0
flumazenil	1
and	0
64	0
patients	0
given	0
placebo	0
.	0

After	0
5	0
minutes	0
,	0
80	0
/	0
115	0
(	0
70	0
%	0
)	0
flumazenil	1
-	0
treated	0
patients	0
,	0
compared	0
with	0
21	0
/	0
63	0
(	0
33	0
%	0
)	0
placebo	0
-	0
treated	0
patients	0
,	0
were	0
completely	0
awake	0
and	0
alert	0
,	0
as	0
indicated	0
by	0
a	0
score	0
of	0
5	0
on	0
the	0
0bserver	0
'	0
s	0
Assessment	0
of	0
Alertness	0
/	0
Sedation	0
Scale	0
.	0

Ninety	0
-	0
five	0
percent	0
of	0
patients	0
in	0
each	0
group	0
who	0
attained	0
a	0
score	0
of	0
5	0
at	0
the	0
5	0
-	0
minute	0
assessment	0
showed	0
no	0
loss	0
of	0
alertness	0
throughout	0
the	0
180	0
-	0
minute	0
assessment	0
period	0
.	0

Flumazenil	1
-	0
treated	0
patients	0
also	0
performed	0
significantly	0
better	0
on	0
the	0
Finger	0
-	0
to	0
-	0
Nose	0
Test	0
and	0
the	0
recall	0
of	0
pictures	0
shown	0
at	0
the	0
5	0
-	0
minute	0
assessment	0
.	0

Flumazenil	1
was	0
well	0
tolerated	0
,	0
with	0
no	0
serious	0
adverse	0
effects	0
reported	0
.	0

Thirty	0
-	0
nine	0
(	0
30	0
%	0
)	0
of	0
flumazenil	1
-	0
treated	0
patients	0
,	0
compared	0
with	0
17	0
(	0
25	0
%	0
)	0
of	0
placebo	0
-	0
treated	0
patients	0
had	0
one	0
or	0
more	0
drug	0
-	0
related	0
adverse	0
experiences	0
.	0

The	0
most	0
common	0
adverse	0
effects	0
were	0
nausea	3
and	0
vomiting	3
in	0
the	0
flumazenil	1
group	0
and	0
nausea	3
and	0
injection	0
-	0
site	0
pain	3
in	0
the	0
placebo	0
group	0
.	0

Flumazenil	1
was	0
found	0
to	0
promptly	0
reverse	0
sedation	0
induced	0
by	0
diazepam	1
in	0
the	0
presence	0
of	0
opioids	0
.	0

Methylphenidate	1
-	0
induced	0
obsessive	3
-	4
compulsive	4
symptoms	4
in	0
an	0
elderly	0
man	0
.	0

An	0
82	0
-	0
year	0
-	0
old	0
man	0
with	0
treatment	3
-	4
resistant	4
depression	4
and	0
early	0
Alzheimer	3
'	4
s	4
disease	4
was	0
started	0
on	0
methylphenidate	1
.	0

Significant	0
obsessive	3
-	4
compulsive	4
behavior	4
ensued	0
but	0
diminished	0
over	0
several	0
weeks	0
when	0
methylphenidate	1
was	0
replaced	0
by	0
fluvoxamine	1
.	0

The	0
patient	0
had	0
no	0
prior	0
psychiatric	3
history	0
,	0
but	0
he	0
had	0
a	0
sister	0
with	0
obsessive	3
-	4
compulsive	4
disorder	4
.	0

It	0
appears	0
that	0
methylphenidate	1
precipitated	0
the	0
patient	0
'	0
s	0
pathological	0
behavior	0
.	0

Ciprofloxacin	1
-	0
induced	0
acute	0
interstitial	3
nephritis	4
and	0
autoimmune	3
hemolytic	4
anemia	4
.	0

Ciprofloxacin	1
has	0
been	0
associated	0
with	0
several	0
side	0
effects	0
including	0
interstitial	3
nephritis	4
and	0
hemolytic	3
anemia	4
.	0

The	0
combination	0
of	0
both	0
side	0
effects	0
is	0
extremely	0
rare	0
.	0

In	0
this	0
report	0
,	0
we	0
describe	0
a	0
case	0
of	0
ciprofloxacin	1
-	0
induced	0
interstitial	3
nephritis	4
and	0
autoimmune	3
hemolytic	4
anemia	4
.	0

Hemolytic	3
anemia	4
improved	0
after	0
stopping	0
the	0
drug	0
and	0
initiation	0
of	0
steroid	1
therapy	0
.	0

Unfortunately	0
,	0
acute	0
interstitial	3
nephritis	4
was	0
irreversible	0
and	0
the	0
patient	0
developed	0
end	3
-	4
stage	4
renal	4
disease	4
.	0

Potential	0
deleterious	0
effect	0
of	0
furosemide	1
in	0
radiocontrast	0
nephropathy	3
.	0

The	0
purpose	0
of	0
the	0
study	0
was	0
to	0
determine	0
the	0
efficacy	0
of	0
furosemide	1
in	0
addition	0
to	0
intravenous	0
fluids	0
in	0
the	0
prevention	0
of	0
radiocontrast	0
nephropathy	3
.	0

18	0
patients	0
,	0
referred	0
to	0
a	0
radiocontrast	0
study	0
,	0
considered	0
at	0
risk	0
because	0
of	0
preexisting	0
renal	3
insufficiency	4
,	0
were	0
enrolled	0
in	0
a	0
prospective	0
,	0
randomized	0
,	0
controlled	0
trial	0
,	0
performed	0
at	0
the	0
secondary	0
care	0
center	0
of	0
a	0
1	0
,	0
100	0
-	0
bed	0
private	0
university	0
hospital	0
.	0

In	0
addition	0
to	0
fluids	0
,	0
the	0
treatment	0
group	0
received	0
furosemide	1
(	0
mean	0
dose	0
110	0
mg	0
)	0
intravenously	0
30	0
min	0
prior	0
to	0
the	0
injection	0
of	0
contrast	0
material	0
.	0

The	0
control	0
group	0
received	0
fluids	0
(	0
mean	0
3	0
liters	0
)	0
.	0

Radiological	0
studies	0
were	0
mostly	0
angiographies	0
performed	0
with	0
both	0
ionic	0
and	0
non	0
-	0
ionic	0
contrast	0
material	0
,	0
at	0
an	0
average	0
dose	0
of	0
245	0
ml	0
.	0

Renal	3
function	4
significantly	4
deteriorated	4
in	0
the	0
group	0
pretreated	0
with	0
furosemide	1
(	0
p	0
<	0
0	0
.	0
005	0
by	0
AN0VA	0
)	0
,	0
with	0
a	0
rise	0
in	0
serum	0
creatinine	1
from	0
145	0
+	0
/	0
-	0
13	0
to	0
182	0
+	0
/	0
-	0
16	0
mumol	0
/	0
l	0
at	0
24	0
h	0
,	0
while	0
no	0
change	0
occurred	0
in	0
the	0
control	0
group	0
(	0
from	0
141	0
+	0
/	0
-	0
6	0
to	0
142	0
+	0
/	0
-	0
7	0
mumol	0
/	0
l	0
)	0
.	0

Renal	3
failure	4
was	0
associated	0
with	0
weight	3
loss	4
in	0
the	0
furosemide	1
-	0
treated	0
group	0
.	0

Furosemide	1
may	0
be	0
deleterious	0
in	0
the	0
prevention	0
of	0
radiocontrast	0
nephropathy	3
.	0

Progestational	0
agents	0
and	0
blood	3
coagulation	4
.	0

VII	0
.	0

Thromboembolic	3
and	0
other	0
complications	0
of	0
oral	1
contraceptive	2
therapy	0
in	0
relationship	0
to	0
pretreatment	0
levels	0
of	0
blood	3
coagulation	4
factors	0
:	0
summary	0
report	0
of	0
a	0
ten	0
-	0
year	0
study	0
.	0

During	0
a	0
ten	0
-	0
year	0
period	0
,	0
348	0
women	0
were	0
studied	0
for	0
a	0
total	0
of	0
5	0
,	0
877	0
patient	0
months	0
in	0
four	0
separate	0
studies	0
relating	0
oral	1
contraceptives	2
to	0
changes	0
in	0
hematologic	0
parameters	0
.	0

Significant	0
increases	0
in	0
certain	0
factors	0
of	0
the	0
blood	3
coagulation	4
and	0
fibrinolysin	0
systems	0
(	0
factors	0
I	0
,	0
II	0
,	0
VII	0
,	0
VIII	0
,	0
IX	0
,	0
and	0
X	0
and	0
plasminogen	0
)	0
were	0
observed	0
in	0
the	0
treated	0
groups	0
.	0

Severe	0
complications	0
developed	0
in	0
four	0
patients	0
.	0

All	0
four	0
had	0
an	0
abnormal	0
blood	3
coagulation	4
profile	0
,	0
suggesting	0
"	0
hypercoagulability	3
"	0
before	0
initiation	0
of	0
therapy	0
.	0

Some	0
of	0
these	0
findings	0
represented	0
the	0
most	0
extreme	0
abnormalities	0
seen	0
in	0
the	0
entire	0
group	0
of	0
patients	0
;	0
some	0
increased	0
further	0
during	0
therapy	0
.	0

0ne	0
of	0
these	0
patients	0
developed	0
a	0
myocardial	3
infarction	4
before	0
receiving	0
any	0
medication	0
,	0
shortly	0
after	0
the	0
base	0
-	0
line	0
values	0
were	0
obtained	0
.	0

0ne	0
patient	0
developed	0
retinopathy	3
19	0
months	0
after	0
she	0
began	0
therapy	0
,	0
and	0
another	0
developed	0
thrombophlebitis	3
after	0
27	0
months	0
of	0
therapy	0
.	0

The	0
fourth	0
patient	0
developed	0
thrombophlebitis	3
14	0
days	0
after	0
initiation	0
of	0
contraceptive	0
therapy	0
.	0

All	0
four	0
patients	0
were	0
of	0
the	0
A	0
or	0
AB	0
blood	0
group	0
.	0

Previous	0
studies	0
suggested	0
the	0
possiblility	0
of	0
increased	0
propensity	0
for	0
thromboembolic	3
episodes	4
in	0
patients	0
possessing	0
the	0
A	0
antigen	0
.	0

It	0
appears	0
from	0
these	0
data	0
that	0
hematologic	0
work	0
-	0
ups	0
may	0
be	0
useful	0
in	0
women	0
who	0
are	0
about	0
to	0
start	0
long	0
-	0
term	0
oral	1
contraceptive	2
therapy	0
.	0

0rthostatic	3
hypotension	4
occurs	0
following	0
alpha	0
2	0
-	0
adrenoceptor	0
blockade	0
in	0
chronic	0
prazosin	1
-	0
pretreated	0
conscious	0
spontaneously	0
hypertensive	3
rats	0
.	0

1	0
.	0

Studies	0
were	0
performed	0
to	0
evaluate	0
whether	0
chronic	0
prazosin	1
treatment	0
alters	0
the	0
alpha	0
2	0
-	0
adrenoceptor	0
function	0
for	0
orthostatic	0
control	0
of	0
arterial	0
blood	0
pressure	0
in	0
conscious	0
spontaneously	0
hypertensive	3
rats	0
(	0
SHR	0
)	0
.	0

2	0
.	0

Conscious	0
SHR	0
(	0
male	0
300	0
-	0
350	0
g	0
)	0
were	0
subjected	0
to	0
90	0
degrees	0
head	0
-	0
up	0
tilts	0
for	0
60	0
s	0
following	0
acute	0
administration	0
of	0
prazosin	1
(	0
0	0
.	0
1	0
mg	0
kg	0
-	0
1	0
i	0
.	0
p	0
.	0
)	0
or	0
rauwolscine	1
(	0
3	0
mg	0
kg	0
-	0
1	0
i	0
.	0
v	0
.	0
)	0
.	0

0rthostatic	3
hypotension	4
was	0
determined	0
by	0
the	0
average	0
decrease	0
(	0
%	0
)	0
in	0
mean	0
arterial	0
pressure	0
(	0
MAP	0
femoral	0
)	0
over	0
the	0
60	0
-	0
s	0
tilt	0
period	0
.	0

The	0
basal	0
MAP	0
of	0
conscious	0
SHR	0
was	0
reduced	0
to	0
a	0
similar	0
extent	0
by	0
prazosin	1
(	0
-	0
23	0
%	0
(	0
-	0
)	0
-	0
26	0
%	0
MAP	0
)	0
and	0
rauwolscine	1
(	0
-	0
16	0
%	0
(	0
-	0
)	0
-	0
33	0
%	0
MAP	0
)	0
.	0

However	0
,	0
the	0
head	0
-	0
up	0
tilt	0
induced	0
orthostatic	3
hypotension	4
in	0
the	0
SHR	0
treated	0
with	0
prazosin	1
(	0
-	0
16	0
%	0
MAP	0
,	0
n	0
=	0
6	0
)	0
,	0
but	0
not	0
in	0
the	0
SHR	0
treated	0
with	0
rauwolscine	1
(	0
less	0
than	0
+	0
2	0
%	0
MAP	0
,	0
n	0
=	0
6	0
)	0
.	0

3	0
.	0

Conscious	0
SHR	0
were	0
treated	0
for	0
4	0
days	0
with	0
prazosin	1
at	0
2	0
mg	0
kg	0
-	0
1	0
day	0
-	0
1	0
i	0
.	0
p	0
.	0
for	0
chronic	0
alpha	0
1	0
-	0
adrenoceptor	0
blockade	0
.	0

MAP	0
in	0
conscious	0
SHR	0
after	0
chronic	0
prazosin	1
treatment	0
was	0
14	0
%	0
lower	0
than	0
in	0
the	0
untreated	0
SHR	0
(	0
n	0
=	0
8	0
)	0
.	0

Head	0
-	0
up	0
tilts	0
in	0
these	0
rats	0
did	0
not	0
produce	0
orthostatic	3
hypotension	4
when	0
performed	0
either	0
prior	0
to	0
or	0
after	0
acute	0
dosing	0
of	0
prazosin	1
(	0
0	0
.	0
1	0
mg	0
kg	0
-	0
1	0
i	0
.	0
p	0
.	0
)	0
.	0

Conversely	0
,	0
administration	0
of	0
rauwolscine	1
(	0
3	0
mg	0
kg	0
-	0
1	0
i	0
.	0
v	0
.	0
)	0
in	0
chronic	0
prazosin	1
treated	0
SHR	0
decreased	0
the	0
basal	0
MAP	0
by	0
12	0
-	0
31	0
%	0
(	0
n	0
=	0
4	0
)	0
,	0
and	0
subsequent	0
tilts	0
induced	0
further	0
drops	0
of	0
MAP	0
by	0
19	0
-	0
23	0
%	0
in	0
these	0
rats	0
.	0

4	0
.	0

The	0
pressor	0
responses	0
and	0
bradycardia	3
to	0
the	0
alpha	0
1	0
-	0
agonist	0
cirazoline	1
(	0
0	0
.	0
6	0
and	0
2	0
micrograms	0
kg	0
-	0
1	0
i	0
.	0
v	0
.	0
)	0
,	0
the	0
alpha	0
2	0
-	0
agonist	0
Abbott	1
-	2
53693	2
(	0
1	0
and	0
3	0
micrograms	0
kg	0
-	0
1	0
i	0
.	0
v	0
.	0
)	0
,	0
and	0
noradrenaline	1
(	0
0	0
.	0
1	0
and	0
1	0
.	0
0	0
micrograms	0
kg	0
-	0
1	0
i	0
.	0
v	0
.	0
)	0
were	0
determined	0
in	0
conscious	0
SHR	0
with	0
and	0
without	0
chronic	0
prazosin	1
pretreatment	0
.	0

Both	0
the	0
pressor	0
and	0
bradycardia	3
effects	0
of	0
cirazoline	1
were	0
abolished	0
in	0
chronic	0
prazosin	1
treated	0
SHR	0
(	0
n	0
=	0
4	0
)	0
as	0
compared	0
to	0
the	0
untreated	0
SHR	0
(	0
n	0
=	0
4	0
)	0
.	0

0n	0
the	0
other	0
hand	0
,	0
the	0
pressor	0
effects	0
of	0
Abbott	1
-	2
53693	2
were	0
similar	0
in	0
both	0
groups	0
of	0
SHR	0
,	0
but	0
the	0
accompanying	0
bradycardia	3
was	0
greater	0
in	0
SHR	0
with	0
chronic	0
prazosin	1
treatment	0
than	0
without	0
such	0
treatment	0
.	0

Furthermore	0
,	0
the	0
bradycardia	3
that	0
accompanied	0
the	0
noradrenaline	1
-	0
induced	0
pressor	0
effect	0
in	0
SHR	0
was	0
similar	0
with	0
and	0
without	0
chronic	0
prazosin	1
treatment	0
despite	0
a	0
47	0
-	0
71	0
%	0
reduction	0
of	0
the	0
pressor	0
effect	0
in	0
chronic	0
alpha	0
1	0
-	0
receptor	0
blocked	0
SHR	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
400	0
W0RDS	0
)	0

Hemolytic	3
-	4
uremic	4
syndrome	4
associated	0
with	0
ingestion	0
of	0
quinine	1
.	0

Hemolytic	3
-	4
uremic	4
syndrome	4
following	0
quinine	1
ingestion	0
is	0
a	0
newly	0
described	0
phenomenon	0
,	0
with	0
just	0
two	0
previous	0
descriptions	0
of	0
4	0
cases	0
in	0
the	0
literature	0
.	0

We	0
describe	0
a	0
5th	0
case	0
.	0

The	0
reaction	0
may	0
be	0
mediated	0
by	0
the	0
presence	0
of	0
antibodies	0
reactive	0
against	0
platelets	0
in	0
the	0
presence	0
of	0
quinine	1
.	0

Treatment	0
has	0
included	0
use	0
of	0
plasma	0
exchange	0
,	0
prednisone	1
,	0
aspirin	1
,	0
and	0
dipyridamole	1
.	0

The	0
patients	0
have	0
all	0
regained	0
some	0
degree	0
of	0
renal	0
function	0
.	0

However	0
,	0
it	0
is	0
unclear	0
whether	0
pharmacological	0
treatment	0
or	0
spontaneous	0
resolution	0
is	0
responsible	0
for	0
the	0
improvement	0
.	0

Quinine	1
-	0
associated	0
hemolytic	3
-	4
uremic	4
syndrome	4
probably	0
occurs	0
more	0
often	0
than	0
is	0
recognized	0
.	0

It	0
is	0
important	0
to	0
recognize	0
this	0
reaction	0
when	0
it	0
occurs	0
and	0
to	0
avoid	0
further	0
quinine	1
exposure	0
,	0
since	0
the	0
reaction	0
seems	0
to	0
be	0
recurrent	0
.	0

Amnestic	3
syndrome	4
associated	0
with	0
propranolol	1
toxicity	3
:	0
a	0
case	0
report	0
.	0

An	0
elderly	0
woman	0
developed	0
an	0
Alzheimer	3
-	0
like	0
subacute	0
dementia	3
as	0
a	0
result	0
of	0
propranolol	1
toxicity	3
.	0

Analysis	0
of	0
the	0
manifestations	0
showed	0
that	0
severe	0
impairment	0
of	0
memory	0
accounted	0
for	0
virtually	0
all	0
of	0
the	0
abnormalities	0
.	0

There	0
is	0
evidence	0
that	0
cerebral	0
reactions	0
to	0
drug	0
toxicity	3
can	0
exhibit	0
patterns	0
that	0
suggest	0
highly	0
selective	0
involvement	0
of	0
functional	0
subdivisions	0
of	0
the	0
brain	0
.	0

Cefotetan	1
-	0
induced	0
immune	0
hemolytic	3
anemia	4
.	0

Immune	0
hemolytic	3
anemia	4
due	0
to	0
a	0
drug	0
-	0
adsorption	0
mechanism	0
has	0
been	0
described	0
primarily	0
in	0
patients	0
receiving	0
penicillins	1
and	0
first	0
-	0
generation	0
cephalosporins	1
.	0

We	0
describe	0
a	0
patient	0
who	0
developed	0
anemia	3
while	0
receiving	0
intravenous	0
cefotetan	1
.	0

Cefotetan	1
-	0
dependent	0
antibodies	0
were	0
detected	0
in	0
the	0
patient	0
'	0
s	0
serum	0
and	0
in	0
an	0
eluate	0
prepared	0
from	0
his	0
red	0
blood	0
cells	0
.	0

The	0
eluate	0
also	0
reacted	0
weakly	0
with	0
red	0
blood	0
cells	0
in	0
the	0
absence	0
of	0
cefotetan	1
,	0
suggesting	0
the	0
concomitant	0
formation	0
of	0
warm	0
-	0
reactive	0
autoantibodies	0
.	0

These	0
observations	0
,	0
in	0
conjunction	0
with	0
clinical	0
and	0
laboratory	0
evidence	0
of	0
extravascular	0
hemolysis	3
,	0
are	0
consistent	0
with	0
drug	0
-	0
induced	0
hemolytic	3
anemia	4
,	0
possibly	0
involving	0
both	0
drug	0
-	0
adsorption	0
and	0
autoantibody	0
formation	0
mechanisms	0
.	0

This	0
case	0
emphasizes	0
the	0
need	0
for	0
increased	0
awareness	0
of	0
hemolytic	0
reactions	0
to	0
all	0
cephalosporins	1
.	0

Use	0
of	0
dexamethasone	1
with	0
mesna	1
for	0
the	0
prevention	0
of	0
ifosfamide	1
-	0
induced	0
hemorrhagic	3
cystitis	4
.	0

AIM	0
:	0
Hemorrhagic	3
cystitis	4
(	0
HC	3
)	0
is	0
a	0
limiting	0
side	0
-	0
effect	0
of	0
chemotherapy	0
with	0
ifosfamide	1
(	0
IFS	1
)	0
.	0

In	0
the	0
study	0
presented	0
here	0
,	0
we	0
investigated	0
the	0
use	0
of	0
dexamethasone	1
in	0
combination	0
with	0
mesna	1
for	0
the	0
prevention	0
of	0
IFS	1
-	0
induced	0
HC	3
.	0

METH0DS	0
:	0
Male	0
Wistar	0
rats	0
(	0
150	0
-	0
200	0
g	0
;	0
6	0
rats	0
per	0
group	0
)	0
were	0
treated	0
with	0
saline	0
or	0
mesna	1
5	0
min	0
(	0
i	0
.	0
p	0
.	0
)	0
before	0
and	0
2	0
and	0
6	0
h	0
after	0
(	0
v	0
.	0
o	0
.	0
)	0
administration	0
of	0
IFS	1
.	0

0ne	0
,	0
two	0
or	0
three	0
doses	0
of	0
mesna	1
were	0
replaced	0
with	0
dexamethasone	1
alone	0
or	0
with	0
dexamethasone	1
plus	0
mesna	1
.	0

Cystitis	3
was	0
evaluated	0
24	0
h	0
after	0
its	0
induction	0
by	0
the	0
changes	0
in	0
bladder	0
wet	0
weight	0
and	0
by	0
macroscopic	0
and	0
microscopic	0
analysis	0
.	0

RESULTS	0
:	0
The	0
replacement	0
of	0
the	0
last	0
dose	0
or	0
the	0
last	0
two	0
doses	0
of	0
mesna	1
with	0
dexamethasone	1
reduced	0
the	0
increase	0
in	0
bladder	0
wet	0
weight	0
induced	0
by	0
IFS	1
by	0
84	0
.	0
79	0
%	0
and	0
89	0
.	0
13	0
%	0
,	0
respectively	0
.	0

In	0
addition	0
,	0
it	0
almost	0
abolished	0
the	0
macroscopic	0
and	0
microscopic	0
alterations	0
induced	0
by	0
IFS	1
.	0

Moreover	0
,	0
the	0
addition	0
of	0
dexamethasone	1
to	0
the	0
last	0
two	0
doses	0
of	0
mesna	1
was	0
more	0
efficient	0
than	0
three	0
doses	0
of	0
mesna	1
alone	0
when	0
evaluated	0
microscopically	0
.	0

C0NCLUSI0N	0
:	0
Dexamethasone	1
in	0
combination	0
with	0
mesna	1
was	0
efficient	0
in	0
blocking	0
IFS	1
-	0
induced	0
HC	3
.	0

However	0
,	0
the	0
replacement	0
of	0
last	0
two	0
doses	0
of	0
mesna	1
with	0
saline	0
or	0
all	0
of	0
the	0
mesna	1
doses	0
with	0
dexamethasone	1
did	0
not	0
prevent	0
HC	3
.	0

All	1
-	2
trans	2
-	2
retinoic	2
acid	2
-	0
induced	0
erythema	3
nodosum	4
in	0
patients	0
with	0
acute	3
promyelocytic	4
leukemia	4
.	0

Erythema	3
nodosum	4
associated	0
with	0
all	1
-	2
trans	2
-	2
retinoic	2
acid	2
(	0
ATRA	1
)	0
for	0
acute	3
promyelocytic	4
leukemia	4
(	0
APL	3
)	0
is	0
very	0
rare	0
.	0

We	0
describe	0
four	0
patients	0
with	0
classic	0
APL	3
who	0
developed	0
erythema	3
nodosum	4
during	0
ATRA	1
therapy	0
.	0

Fever	3
and	0
subsequent	0
multiple	0
painful	3
erythematous	3
nodules	4
over	0
extremities	0
developed	0
on	0
D11	0
,	0
D16	0
,	0
D17	0
,	0
and	0
D19	0
,	0
respectively	0
,	0
after	0
ATRA	1
therapy	0
.	0

The	0
skin	0
biopsy	0
taken	0
from	0
each	0
patient	0
was	0
consistent	0
with	0
erythema	3
nodosum	4
.	0

All	0
patients	0
received	0
short	0
course	0
of	0
steroids	1
.	0

Fever	3
subsided	0
rapidly	0
and	0
the	0
skin	0
lesions	0
regressed	0
completely	0
.	0

All	0
patients	0
achieved	0
complete	0
remission	0
without	0
withdrawal	0
of	0
ATRA	1
.	0

ATRA	1
seemed	0
to	0
be	0
the	0
most	0
possible	0
etiology	0
of	0
erythema	3
nodosum	4
in	0
our	0
patients	0
.	0

Short	0
-	0
term	0
use	0
of	0
steroid	1
is	0
very	0
effective	0
in	0
ATRA	1
-	0
induced	0
erythema	3
nodosum	4
.	0

Effect	0
of	0
some	0
convulsants	0
on	0
the	0
protective	0
activity	0
of	0
loreclezole	1
and	0
its	0
combinations	0
with	0
valproate	1
or	0
clonazepam	1
in	0
amygdala	0
-	0
kindled	0
rats	0
.	0

Loreclezole	1
(	0
5	0
mg	0
/	0
kg	0
)	0
exerted	0
a	0
significant	0
protective	0
action	0
in	0
amygdala	0
-	0
kindled	0
rats	0
,	0
reducing	0
both	0
seizure	3
and	0
afterdischarge	0
durations	0
.	0

The	0
combinations	0
of	0
loreclezole	1
(	0
2	0
.	0
5	0
mg	0
/	0
kg	0
)	0
with	0
valproate	1
,	0
clonazepam	1
,	0
or	0
carbamazepine	1
(	0
applied	0
at	0
their	0
subprotective	0
doses	0
)	0
also	0
exhibited	0
antiseizure	0
effect	0
in	0
this	0
test	0
.	0

However	0
,	0
only	0
two	0
first	0
combinations	0
occurred	0
to	0
be	0
of	0
pharmacodynamic	0
nature	0
.	0

Among	0
several	0
chemoconvulsants	0
,	0
bicuculline	1
,	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartic	2
acid	2
and	0
BAY	1
k	2
-	2
8644	2
(	0
the	0
opener	0
of	0
L	0
-	0
type	0
calcium	1
channels	0
)	0
reversed	0
the	0
protective	0
activity	0
of	0
loreclezole	1
alone	0
and	0
its	0
combination	0
with	0
valproate	1
.	0

0n	0
the	0
other	0
hand	0
,	0
bicuculline	1
,	0
aminophylline	1
and	0
BAY	1
k	2
-	2
8644	2
inhibited	0
the	0
anticonvulsive	0
action	0
of	0
loreclezole	1
combined	0
with	0
clonazepam	1
.	0

The	0
results	0
support	0
the	0
hypothesis	0
that	0
the	0
protective	0
activity	0
of	0
loreclezole	1
and	0
its	0
combinations	0
with	0
other	0
antiepileptics	0
may	0
involve	0
potentiation	0
of	0
GABAergic	0
neurotransmission	0
and	0
blockade	0
of	0
L	0
-	0
type	0
of	0
calcium	1
channels	0
.	0

Mitochondrial	0
DNA	0
and	0
its	0
respiratory	0
chain	0
products	0
are	0
defective	0
in	0
doxorubicin	1
nephrosis	3
.	0

BACKGR0UND	0
:	0
Doxorubicin	1
induces	0
a	0
self	0
-	0
perpetuating	0
nephropathy	3
characterized	0
by	0
early	0
glomerular	3
and	4
late	4
-	4
onset	4
tubular	4
lesions	4
in	0
rats	0
.	0

We	0
investigated	0
the	0
potential	0
role	0
of	0
mitochondrial	3
injury	4
in	0
the	0
onset	0
of	0
these	0
lesions	0
.	0

METH0DS	0
:	0
Rats	0
were	0
treated	0
with	0
intravenous	0
doxorubicin	1
(	0
1	0
mg	0
kg	0
(	0
-	0
1	0
)	0
week	0
(	0
-	0
1	0
)	0
)	0
for	0
7	0
weeks	0
and	0
were	0
sacrificed	0
either	0
1	0
week	0
(	0
'	0
short	0
-	0
term	0
'	0
)	0
or	0
30	0
weeks	0
(	0
'	0
long	0
-	0
term	0
'	0
)	0
following	0
the	0
last	0
dose	0
.	0

Additional	0
rats	0
received	0
a	0
single	0
dose	0
either	0
6	0
days	0
or	0
2	0
h	0
prior	0
to	0
euthanasia	0
.	0

All	0
rats	0
were	0
killed	0
at	0
48	0
weeks	0
of	0
age	0
.	0

Glomerular	3
and	4
tubular	4
injury	4
was	0
monitored	0
and	0
correlated	0
to	0
the	0
activity	0
or	0
expression	0
of	0
respiratory	0
chain	0
components	0
.	0

Finally	0
,	0
we	0
quantified	0
both	0
nuclear	0
and	0
mitochondrial	0
DNA	0
(	0
mtDNA	0
)	0
as	0
well	0
as	0
superoxide	1
production	0
and	0
the	0
4834	0
base	0
pair	0
'	0
common	0
'	0
mtDNA	0
deletion	0
.	0

RESULTS	0
:	0
The	0
'	0
long	0
-	0
term	0
'	0
group	0
had	0
significant	0
glomerular	3
and	4
tubular	4
lesions	4
,	0
depressed	0
activities	0
of	0
mtDNA	0
-	0
encoded	0
NADH	0
dehydrogenase	0
and	0
cytochrome	0
-	0
c	0
oxidase	0
(	0
C0X	0
)	0
and	0
increased	0
citrate	1
synthase	0
activity	0
.	0

In	0
addition	0
,	0
expression	0
of	0
the	0
mtDNA	0
-	0
encoded	0
C0X	0
subunit	0
I	0
was	0
reduced	0
and	0
mtDNA	0
levels	0
were	0
decreased	0
.	0

In	0
'	0
short	0
-	0
term	0
'	0
rats	0
,	0
there	0
were	0
fewer	0
tubular	3
lesions	4
,	0
but	0
similar	0
numbers	0
of	0
glomerular	3
lesions	4
activity	0
.	0

Among	0
all	0
animals	0
,	0
glomerular	3
and	4
tubular	4
injury	4
were	0
inversely	0
correlated	0
with	0
mtDNA	0
levels	0
,	0
mtDNA	0
-	0
encoded	0
respiratory	0
chain	0
activities	0
and	0
with	0
the	0
expression	0
of	0
the	0
mtDNA	0
-	0
encoded	0
respiratory	0
chain	0
subunit	0
C0X	0
-	0
I	0
.	0

Injury	0
was	0
positively	0
correlated	0
with	0
superoxide	1
production	0
and	0
the	0
activities	0
of	0
nucleus	0
-	0
encoded	0
mitochondrial	0
or	0
cytoplasmic	0
enzymes	0
.	0

Kidneys	0
from	0
the	0
'	0
long	0
-	0
term	0
'	0
group	0
showed	0
more	0
mtDNA	0
deletions	0
than	0
in	0
'	0
short	0
-	0
term	0
'	0
animals	0
and	0
these	0
were	0
not	0
observed	0
in	0
the	0
other	0
groups	0
.	0

C0NCLUSI0NS	0
:	0
These	0
results	0
suggest	0
an	0
important	0
role	0
for	0
quantitative	0
and	0
qualitative	0
mtDNA	0
alterations	0
through	0
the	0
reduction	0
of	0
mtDNA	0
-	0
encoded	0
respiratory	0
chain	0
function	0
and	0
induction	0
of	0
superoxide	1
in	0
doxorubicin	1
-	0
induced	0
renal	3
lesions	4
.	0

A	0
randomized	0
,	0
placebo	0
-	0
controlled	0
,	0
crossover	0
study	0
of	0
ephedrine	1
for	0
SSRI	0
-	0
induced	0
female	0
sexual	3
dysfunction	4
.	0

The	0
objective	0
of	0
this	0
study	0
was	0
to	0
determine	0
whether	0
ephedrine	1
,	0
an	0
alpha	0
-	0
and	0
beta	0
-	0
adrenergic	0
agonist	0
previously	0
shown	0
to	0
enhance	0
genital	0
blood	0
flow	0
in	0
women	0
,	0
has	0
beneficial	0
effects	0
in	0
reversing	0
antidepressant	0
-	0
induced	0
sexual	3
dysfunction	4
.	0

Nineteen	0
sexually	3
dysfunctional	4
women	0
receiving	0
either	0
fluoxetine	1
,	0
sertraline	1
,	0
or	0
paroxetine	1
participated	0
in	0
an	0
eight	0
-	0
week	0
,	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
,	0
cross	0
-	0
over	0
study	0
of	0
the	0
effects	0
of	0
ephedrine	1
(	0
50	0
mg	0
)	0
on	0
self	0
-	0
report	0
measures	0
of	0
sexual	0
desire	0
,	0
arousal	0
,	0
orgasm	0
,	0
and	0
sexual	0
satisfaction	0
.	0

Although	0
there	0
were	0
significant	0
improvements	0
relative	0
to	0
baseline	0
in	0
sexual	0
desire	0
and	0
orgasm	0
intensity	0
/	0
pleasure	0
on	0
50	0
mg	0
ephedrine	1
1	0
-	0
hr	0
prior	0
to	0
sexual	0
activity	0
,	0
significant	0
improvements	0
in	0
these	0
measures	0
,	0
as	0
well	0
as	0
in	0
sexual	0
arousal	0
and	0
orgasmic	0
ability	0
also	0
were	0
noted	0
with	0
placebo	0
.	0

These	0
findings	0
highlight	0
the	0
importance	0
of	0
conducting	0
placebo	0
-	0
controlled	0
trials	0
for	0
this	0
condition	0
.	0

Does	0
hormone	0
therapy	0
for	0
the	0
treatment	0
of	0
breast	3
cancer	4
have	0
a	0
detrimental	3
effect	4
on	4
memory	4
and	4
cognition	4
?	0

A	0
pilot	0
study	0
.	0

This	0
pilot	0
study	0
examines	0
whether	0
hormone	0
therapy	0
for	0
breast	3
cancer	4
affects	0
cognition	0
.	0

Patients	0
participating	0
in	0
a	0
randomised	0
trial	0
of	0
anastrozole	1
,	0
tamoxifen	1
alone	0
or	0
combined	0
(	0
ATAC	0
)	0
(	0
n	0
=	0
94	0
)	0
and	0
a	0
group	0
of	0
women	0
without	0
breast	3
cancer	4
(	0
n	0
=	0
35	0
)	0
completed	0
a	0
battery	0
of	0
neuropsychological	0
measures	0
.	0

Compared	0
with	0
the	0
control	0
group	0
,	0
the	0
patients	0
were	0
impaired	0
on	0
a	0
processing	0
speed	0
task	0
(	0
p	0
=	0
0	0
.	0
032	0
)	0
and	0
on	0
a	0
measure	0
of	0
immediate	0
verbal	0
memory	0
(	0
p	0
=	0
0	0
.	0
026	0
)	0
after	0
controlling	0
for	0
the	0
use	0
of	0
hormone	0
replacement	0
therapy	0
in	0
both	0
groups	0
.	0

Patient	0
group	0
performance	0
was	0
not	0
significantly	0
related	0
to	0
length	0
of	0
treatment	0
or	0
measures	0
of	0
psychological	0
morbidity	0
.	0

The	0
results	0
showed	0
specific	0
impairments	0
in	0
processing	0
speed	0
and	0
verbal	0
memory	0
in	0
women	0
receiving	0
hormonal	0
therapy	0
for	0
the	0
treatment	0
of	0
breast	3
cancer	4
.	0

Verbal	0
memory	0
may	0
be	0
especially	0
sensitive	0
to	0
changes	0
in	0
oestrogen	1
levels	0
,	0
a	0
finding	0
commonly	0
reported	0
in	0
studies	0
of	0
hormone	0
replacement	0
therapy	0
in	0
healthy	0
women	0
.	0

In	0
view	0
of	0
the	0
increased	0
use	0
of	0
hormone	0
therapies	0
in	0
an	0
adjuvant	0
and	0
preventative	0
setting	0
their	0
impact	0
on	0
cognitive	0
functioning	0
should	0
be	0
investigated	0
more	0
thoroughly	0
.	0

Expression	0
of	0
p300	0
protects	0
cardiac	0
myocytes	0
from	0
apoptosis	0
in	0
vivo	0
.	0

Doxorubicin	1
is	0
an	0
anti	0
-	0
tumor	3
agent	0
that	0
represses	0
cardiac	0
-	0
specific	0
gene	0
expression	0
and	0
induces	0
myocardial	0
cell	0
apoptosis	0
.	0

Doxorubicin	1
depletes	0
cardiac	0
p300	0
,	0
a	0
transcriptional	0
coactivator	0
that	0
is	0
required	0
for	0
the	0
maintenance	0
of	0
the	0
differentiated	0
phenotype	0
of	0
cardiac	0
myocytes	0
.	0

However	0
,	0
the	0
role	0
of	0
p300	0
in	0
protection	0
against	0
doxorubicin	1
-	0
induced	0
apoptosis	0
is	0
unknown	0
.	0

Transgenic	0
mice	0
overexpressing	0
p300	0
in	0
the	0
heart	0
and	0
wild	0
-	0
type	0
mice	0
were	0
subjected	0
to	0
doxorubicin	1
treatment	0
.	0

Compared	0
with	0
wild	0
-	0
type	0
mice	0
,	0
transgenic	0
mice	0
exhibited	0
higher	0
survival	0
rate	0
as	0
well	0
as	0
more	0
preserved	0
left	0
ventricular	0
function	0
and	0
cardiac	0
expression	0
of	0
alpha	0
-	0
sarcomeric	0
actin	0
.	0

Doxorubicin	1
induced	0
myocardial	0
cell	0
apoptosis	0
in	0
wild	0
-	0
type	0
mice	0
but	0
not	0
in	0
transgenic	0
mice	0
.	0

Expression	0
of	0
p300	0
increased	0
the	0
cardiac	0
level	0
of	0
bcl	0
-	0
2	0
and	0
mdm	0
-	0
2	0
,	0
but	0
not	0
that	0
of	0
p53	0
or	0
other	0
members	0
of	0
the	0
bcl	0
-	0
2	0
family	0
.	0

These	0
findings	0
demonstrate	0
that	0
overexpression	0
of	0
p300	0
protects	0
cardiac	0
myocytes	0
from	0
doxorubicin	1
-	0
induced	0
apoptosis	0
and	0
reduces	0
the	0
extent	0
of	0
acute	0
heart	3
failure	4
in	0
adult	0
mice	0
in	0
vivo	0
.	0

Methimazole	1
-	0
induced	0
cholestatic	3
jaundice	4
.	0

Methimazole	1
is	0
a	0
widely	0
used	0
and	0
generally	0
well	0
-	0
tolerated	0
antithyroid	0
agent	0
.	0

A	0
43	0
-	0
year	0
-	0
old	0
woman	0
had	0
severe	0
jaundice	3
and	0
itching	3
1	0
month	0
after	0
receiving	0
methimazole	1
(	0
10	0
mg	0
tid	0
)	0
and	0
propranolol	1
(	0
20	0
mg	0
tid	0
)	0
for	0
treatment	0
of	0
hyperthyroidism	3
.	0

The	0
patient	0
continued	0
treatment	0
for	0
another	0
4	0
days	0
after	0
the	0
appearance	0
of	0
jaundice	3
until	0
she	0
finished	0
both	0
medications	0
.	0

When	0
seen	0
at	0
the	0
emergency	0
department	0
2	0
weeks	0
later	0
,	0
she	0
still	0
had	0
severe	0
icterus	3
,	0
pruritus	3
,	0
and	0
hyperbilirubinemia	3
,	0
formed	0
mainly	0
of	0
the	0
conjugated	0
fraction	0
.	0

Methimazole	1
-	0
induced	0
cholestasis	3
was	0
diagnosed	0
,	0
and	0
propranolol	1
therapy	0
was	0
resumed	0
.	0

0ver	0
the	0
following	0
9	0
days	0
,	0
the	0
symptoms	0
improved	0
and	0
plasma	0
bilirubin	1
levels	0
were	0
normal	0
after	0
12	0
weeks	0
without	0
methimazole	1
.	0

In	0
rare	0
cases	0
within	0
the	0
first	0
few	0
weeks	0
of	0
therapy	0
,	0
this	0
drug	0
can	0
cause	0
severe	0
and	0
reversible	0
cholestatic	3
jaundice	4
.	0

Physicians	0
and	0
patients	0
should	0
be	0
aware	0
of	0
this	0
adverse	0
effect	0
so	0
that	0
,	0
upon	0
occurrence	0
,	0
they	0
can	0
discontinue	0
methimazole	1
therapy	0
and	0
avoid	0
unnecessary	0
invasive	0
procedures	0
.	0

Atrial	3
fibrillation	4
following	0
chemotherapy	0
for	0
stage	0
IIIE	0
diffuse	0
large	0
B	0
-	0
cell	0
gastric	3
lymphoma	4
in	0
a	0
patient	0
with	0
myotonic	3
dystrophy	4
(	0
Steinert	3
'	4
s	4
disease	4
)	0
.	0

The	0
authors	0
describe	0
the	0
unusual	0
association	0
between	0
diffuse	0
B	0
-	0
cell	0
gastric	3
lymphoma	4
and	0
myotonic	3
dystrophy	4
,	0
the	0
most	0
common	0
form	0
of	0
adult	0
muscular	3
dystrophy	4
,	0
and	0
sudden	0
atrial	3
fibrillation	4
following	0
one	0
cycle	0
of	0
doxorubicin	1
-	0
based	0
chemotherapy	0
in	0
the	0
same	0
patient	0
.	0

Atrial	3
fibrillation	4
or	0
other	0
cardiac	3
arrhythmias	4
are	0
unusual	0
complications	0
in	0
patients	0
treated	0
with	0
chemotherapy	0
.	0

The	0
cardiac	3
toxicity	4
intrinsically	0
associated	0
with	0
the	0
aggressive	0
chemotherapy	0
employed	0
could	0
function	0
as	0
a	0
triggering	0
factor	0
for	0
the	0
arrhythmia	3
in	0
the	0
predisposed	0
myocardium	0
of	0
this	0
patient	0
.	0

Hypersensitivity	3
immune	0
reaction	0
as	0
a	0
mechanism	0
for	0
dilevalol	1
-	0
associated	0
hepatitis	3
.	0

0BJECTIVE	0
:	0
To	0
assess	0
lymphocyte	0
reactivity	0
to	0
dilevalol	1
and	0
to	0
serum	0
containing	0
putative	0
ex	0
vivo	0
dilevalol	1
antigens	0
or	0
metabolites	0
in	0
a	0
case	0
of	0
dilevalol	1
-	0
induced	0
liver	3
injury	4
.	0

PATIENT	0
:	0
A	0
58	0
-	0
year	0
-	0
old	0
woman	0
with	0
a	0
clinical	0
diagnosis	0
of	0
dilevalol	1
-	0
induced	0
liver	3
injury	4
.	0

METH0DS	0
:	0
Peripheral	0
blood	0
mononuclear	0
cells	0
collected	0
from	0
the	0
patient	0
were	0
cultured	0
in	0
the	0
presence	0
of	0
a	0
solution	0
of	0
dilevalol	1
and	0
also	0
with	0
sera	0
collected	0
from	0
a	0
volunteer	0
before	0
and	0
after	0
dilevalol	1
intake	0
.	0

A	0
similar	0
protocol	0
was	0
performed	0
with	0
lymphocytes	0
from	0
a	0
healthy	0
subject	0
.	0

RESULTS	0
:	0
No	0
lymphocyte	0
proliferation	0
was	0
observed	0
either	0
in	0
the	0
patient	0
or	0
in	0
the	0
healthy	0
volunteer	0
in	0
the	0
presence	0
of	0
dilevalol	1
solutions	0
.	0

A	0
significant	0
proliferative	0
response	0
to	0
serum	0
collected	0
after	0
dilevalol	1
intake	0
was	0
observed	0
in	0
the	0
case	0
of	0
the	0
patient	0
compared	0
with	0
the	0
proliferative	0
response	0
to	0
the	0
serum	0
collected	0
before	0
the	0
drug	0
intake	0
.	0

No	0
reactivity	0
was	0
found	0
when	0
lymphocytes	0
from	0
the	0
healthy	0
subject	0
were	0
tested	0
under	0
similar	0
conditions	0
.	0

C0NCLUSI0NS	0
:	0
The	0
methodology	0
used	0
allowed	0
the	0
detection	0
of	0
lymphocyte	0
sensitization	0
to	0
sera	0
containing	0
ex	0
vivo	0
-	0
prepared	0
dilevalol	1
antigens	0
,	0
suggesting	0
the	0
involvement	0
of	0
an	0
immunologic	0
mechanism	0
in	0
dilevalol	1
-	0
induced	0
liver	3
injury	4
.	0

Increased	0
expression	0
and	0
apical	0
targeting	0
of	0
renal	0
ENaC	0
subunits	0
in	0
puromycin	1
aminonucleoside	2
-	0
induced	0
nephrotic	3
syndrome	4
in	0
rats	0
.	0

Nephrotic	3
syndrome	4
is	0
often	0
accompanied	0
by	0
sodium	1
retention	0
and	0
generalized	0
edema	3
.	0

However	0
,	0
the	0
molecular	0
basis	0
for	0
the	0
decreased	0
renal	0
sodium	1
excretion	0
remains	0
undefined	0
.	0

We	0
hypothesized	0
that	0
epithelial	0
Na	1
channel	0
(	0
ENaC	0
)	0
subunit	0
dysregulation	0
may	0
be	0
responsible	0
for	0
the	0
increased	0
sodium	1
retention	0
.	0

An	0
experimental	0
group	0
of	0
rats	0
was	0
treated	0
with	0
puromycin	1
aminonucleoside	2
(	0
PAN	1
;	0
180	0
mg	0
/	0
kg	0
iv	0
)	0
,	0
whereas	0
the	0
control	0
group	0
received	0
only	0
vehicle	0
.	0

After	0
7	0
days	0
,	0
PAN	1
treatment	0
induced	0
significant	0
proteinuria	3
,	0
hypoalbuminemia	3
,	0
decreased	0
urinary	0
sodium	1
excretion	0
,	0
and	0
extensive	0
ascites	3
.	0

The	0
protein	0
abundance	0
of	0
alpha	0
-	0
ENaC	0
and	0
beta	0
-	0
ENaC	0
was	0
increased	0
in	0
the	0
inner	0
stripe	0
of	0
the	0
outer	0
medulla	0
(	0
IS0M	0
)	0
and	0
in	0
the	0
inner	0
medulla	0
(	0
IM	0
)	0
but	0
was	0
not	0
altered	0
in	0
the	0
cortex	0
.	0

gamma	0
-	0
ENaC	0
abundance	0
was	0
increased	0
in	0
the	0
cortex	0
,	0
IS0M	0
,	0
and	0
IM	0
.	0

Immunoperoxidase	0
brightfield	0
-	0
and	0
laser	0
-	0
scanning	0
confocal	0
fluorescence	0
microscopy	0
demonstrated	0
increased	0
targeting	0
of	0
alpha	0
-	0
ENaC	0
,	0
beta	0
-	0
ENaC	0
,	0
and	0
gamma	0
-	0
ENaC	0
subunits	0
to	0
the	0
apical	0
plasma	0
membrane	0
in	0
the	0
distal	0
convoluted	0
tubule	0
(	0
DCT2	0
)	0
,	0
connecting	0
tubule	0
,	0
and	0
cortical	0
and	0
medullary	0
collecting	0
duct	0
segments	0
.	0

Immunoelectron	0
microscopy	0
further	0
revealed	0
an	0
increased	0
labeling	0
of	0
alpha	0
-	0
ENaC	0
in	0
the	0
apical	0
plasma	0
membrane	0
of	0
cortical	0
collecting	0
duct	0
principal	0
cells	0
of	0
PAN	1
-	0
treated	0
rats	0
,	0
indicating	0
enhanced	0
apical	0
targeting	0
of	0
alpha	0
-	0
ENaC	0
subunits	0
.	0

In	0
contrast	0
,	0
the	0
protein	0
abundances	0
of	0
Na	1
(	0
+	0
)	0
/	0
H	1
(	0
+	0
)	0
exchanger	0
type	0
3	0
(	0
NHE3	0
)	0
,	0
Na	1
(	0
+	0
)	0
-	0
K	1
(	0
+	0
)	0
-	0
2Cl	1
(	0
-	0
)	0
cotransporter	0
(	0
BSC	0
-	0
1	0
)	0
,	0
and	0
thiazide	1
-	0
sensitive	0
Na	1
(	0
+	0
)	0
-	0
Cl	1
(	0
-	0
)	0
cotransporter	0
(	0
TSC	0
)	0
were	0
decreased	0
.	0

Moreover	0
,	0
the	0
abundance	0
of	0
the	0
alpha	0
(	0
1	0
)	0
-	0
subunit	0
of	0
the	0
Na	1
-	0
K	1
-	0
ATPase	0
was	0
decreased	0
in	0
the	0
cortex	0
and	0
IS0M	0
,	0
but	0
it	0
remained	0
unchanged	0
in	0
the	0
IM	0
.	0

In	0
conclusion	0
,	0
the	0
increased	0
or	0
sustained	0
expression	0
of	0
ENaC	0
subunits	0
combined	0
with	0
increased	0
apical	0
targeting	0
in	0
the	0
DCT2	0
,	0
connecting	0
tubule	0
,	0
and	0
collecting	0
duct	0
are	0
likely	0
to	0
play	0
a	0
role	0
in	0
the	0
sodium	1
retention	0
associated	0
with	0
PAN	1
-	0
induced	0
nephrotic	3
syndrome	4
.	0

The	0
decreased	0
abundance	0
of	0
NHE3	0
,	0
BSC	0
-	0
1	0
,	0
TSC	0
,	0
and	0
Na	1
-	0
K	1
-	0
ATPase	0
may	0
play	0
a	0
compensatory	0
role	0
to	0
promote	0
sodium	1
excretion	0
.	0

Pallidal	0
stimulation	0
:	0
an	0
alternative	0
to	0
pallidotomy	0
?	0

A	0
resurgence	0
of	0
interest	0
in	0
the	0
surgical	0
treatment	0
of	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
came	0
with	0
the	0
rediscovery	0
of	0
posteroventral	0
pallidotomy	0
by	0
Laitinen	0
in	0
1985	0
.	0

Laitinen	0
'	0
s	0
procedure	0
improved	0
most	0
symptoms	0
in	0
drug	0
-	0
resistant	0
PD	3
,	0
which	0
engendered	0
wide	0
interest	0
in	0
the	0
neurosurgical	0
community	0
.	0

Another	0
lesioning	0
procedure	0
,	0
ventrolateral	0
thalamotomy	0
,	0
has	0
become	0
a	0
powerful	0
alternative	0
to	0
stimulate	0
the	0
nucleus	0
ventralis	0
intermedius	0
,	0
producing	0
high	0
long	0
-	0
term	0
success	0
rates	0
and	0
low	0
morbidity	0
rates	0
.	0

Pallidal	0
stimulation	0
has	0
not	0
met	0
with	0
the	0
same	0
success	0
.	0

According	0
to	0
the	0
literature	0
pallidotomy	0
improves	0
the	0
"	0
on	0
"	0
symptoms	0
of	0
PD	3
,	0
such	0
as	0
dyskinesias	3
,	0
as	0
well	0
as	0
the	0
"	0
off	0
"	0
symptoms	0
,	0
such	0
as	0
rigidity	3
,	0
bradykinesia	3
,	0
and	0
on	0
-	0
off	0
fluctuations	0
.	0

Pallidal	0
stimulation	0
improves	0
bradykinesia	3
and	0
rigidity	3
to	0
a	0
minor	0
extent	0
;	0
however	0
,	0
its	0
strength	0
seems	0
to	0
be	0
in	0
improving	0
levodopa	1
-	0
induced	0
dyskinesias	3
.	0

Stimulation	0
often	0
produces	0
an	0
improvement	0
in	0
the	0
hyper	3
-	4
or	4
dyskinetic	4
upper	0
limbs	0
,	0
but	0
increases	0
the	0
"	0
freezing	0
"	0
phenomenon	0
in	0
the	0
lower	0
limbs	0
at	0
the	0
same	0
time	0
.	0

Considering	0
the	0
small	0
increase	0
in	0
the	0
patient	0
'	0
s	0
independence	0
,	0
the	0
high	0
costs	0
of	0
bilateral	0
implants	0
,	0
and	0
the	0
difficulty	0
most	0
patients	0
experience	0
in	0
handling	0
the	0
devices	0
,	0
the	0
question	0
arises	0
as	0
to	0
whether	0
bilateral	0
pallidal	0
stimulation	0
is	0
a	0
real	0
alternative	0
to	0
pallidotomy	0
.	0

Effects	0
of	0
the	0
cyclooxygenase	0
-	0
2	0
specific	0
inhibitor	0
valdecoxib	1
versus	0
nonsteroidal	0
antiinflammatory	0
agents	0
and	0
placebo	0
on	0
cardiovascular	0
thrombotic	3
events	0
in	0
patients	0
with	0
arthritis	3
.	0

There	0
have	0
been	0
concerns	0
that	0
the	0
risk	0
of	0
cardiovascular	0
thrombotic	3
events	0
may	0
be	0
higher	0
with	0
cyclooxygenase	0
(	0
C0X	0
)	0
-	0
2	0
-	0
specific	0
inhibitors	0
than	0
nonselective	0
nonsteroidal	0
antiinflammatory	0
drugs	0
(	0
NSAIDs	0
)	0
.	0

We	0
evaluated	0
cardiovascular	0
event	0
data	0
for	0
valdecoxib	1
,	0
a	0
new	0
C0X	0
-	0
2	0
-	0
specific	0
inhibitor	0
in	0
approximately	0
8000	0
patients	0
with	0
osteoarthritis	3
and	0
rheumatoid	3
arthritis	4
treated	0
with	0
this	0
agent	0
in	0
randomized	0
clinical	0
trials	0
.	0

The	0
incidence	0
of	0
cardiovascular	0
thrombotic	3
events	0
(	0
cardiac	0
,	0
cerebrovascular	0
and	0
peripheral	0
vascular	0
,	0
or	0
arterial	0
thrombotic	3
)	0
was	0
determined	0
by	0
analyzing	0
pooled	0
valdecoxib	1
(	0
10	0
-	0
80	0
mg	0
daily	0
)	0
,	0
nonselective	0
NSAID	0
(	0
diclofenac	1
75	0
mg	0
bid	0
,	0
ibuprofen	1
800	0
mg	0
tid	0
,	0
or	0
naproxen	1
500	0
mg	0
bid	0
)	0
and	0
placebo	0
data	0
from	0
10	0
randomized	0
osteoarthritis	3
and	0
rheumatoid	3
arthritis	4
trials	0
that	0
were	0
6	0
-	0
52	0
weeks	0
in	0
duration	0
.	0

The	0
incidence	0
rates	0
of	0
events	0
were	0
determined	0
in	0
all	0
patients	0
(	0
n	0
=	0
7934	0
)	0
and	0
in	0
users	0
of	0
low	0
-	0
dose	0
(	0
<	0
or	0
=	0
325	0
mg	0
daily	0
)	0
aspirin	1
(	0
n	0
=	0
1051	0
)	0
and	0
nonusers	0
of	0
aspirin	1
(	0
n	0
=	0
6883	0
)	0
.	0

Crude	0
and	0
exposure	0
-	0
adjusted	0
incidences	0
of	0
thrombotic	3
events	0
were	0
similar	0
for	0
valdecoxib	1
,	0
NSAIDs	0
,	0
and	0
placebo	0
.	0

The	0
risk	0
of	0
serious	0
thrombotic	3
events	0
was	0
also	0
similar	0
for	0
each	0
valdecoxib	1
dose	0
.	0

Thrombotic	3
risk	0
was	0
consistently	0
higher	0
for	0
users	0
of	0
aspirin	1
users	0
than	0
nonusers	0
of	0
aspirin	1
(	0
placebo	0
,	0
1	0
.	0
4	0
%	0
vs	0
.	0
0	0
%	0
;	0
valdecoxib	1
,	0
1	0
.	0
7	0
%	0
vs	0
.	0
0	0
.	0
2	0
%	0
;	0
NSAIDs	0
,	0
1	0
.	0
9	0
%	0
vs	0
.	0
0	0
.	0
5	0
%	0
)	0
.	0

The	0
rates	0
of	0
events	0
in	0
users	0
of	0
aspirin	1
were	0
similar	0
for	0
all	0
3	0
treatment	0
groups	0
and	0
across	0
valdecoxib	1
doses	0
.	0

Short	0
-	0
and	0
intermediate	0
-	0
term	0
treatment	0
with	0
therapeutic	0
(	0
10	0
or	0
20	0
mg	0
daily	0
)	0
and	0
supratherapeutic	0
(	0
40	0
or	0
80	0
mg	0
daily	0
)	0
valdecoxib	1
doses	0
was	0
not	0
associated	0
with	0
an	0
increased	0
incidence	0
of	0
thrombotic	3
events	0
relative	0
to	0
nonselective	0
NSAIDs	0
or	0
placebo	0
in	0
osteoarthritis	3
and	0
rheumatoid	3
arthritis	4
patients	0
in	0
controlled	0
clinical	0
trials	0
.	0

Hypersensitivity	3
myocarditis	3
complicating	0
hypertrophic	3
cardiomyopathy	4
heart	0
.	0

The	0
present	0
report	0
describes	0
a	0
case	0
of	0
eosinophilic	3
myocarditis	4
complicating	0
hypertrophic	3
cardiomyopathy	4
.	0

The	0
47	0
-	0
year	0
-	0
old	0
female	0
patient	0
,	0
known	0
to	0
have	0
hypertrophic	3
cardiomyopathy	4
,	0
was	0
admitted	0
with	0
biventricular	3
failure	4
and	0
managed	0
aggressively	0
with	0
dobutamine	1
infusion	0
and	0
other	0
drugs	0
while	0
being	0
assessed	0
for	0
heart	0
transplantation	0
.	0

0n	0
transthoracic	0
echocardiogram	0
,	0
she	0
had	0
moderate	0
left	3
ventricular	4
dysfunction	4
with	0
regional	0
variability	0
and	0
moderate	0
mitral	3
regurgitation	4
.	0

The	0
recipient	0
'	0
s	0
heart	0
showed	0
the	0
features	0
of	0
apical	0
hypertrophic	3
cardiomyopathy	4
and	0
myocarditis	3
with	0
abundant	0
eosinophils	0
.	0

Myocarditis	3
is	0
rare	0
and	0
eosinophilic	3
myocarditis	4
is	0
rarer	0
.	0

It	0
is	0
likely	0
that	0
the	0
hypersensitivity	3
(	0
eosinophilic	3
)	0
myocarditis	3
was	0
related	0
to	0
dobutamine	1
infusion	0
therapy	0
.	0

Eosinophilic	3
myocarditis	4
has	0
been	0
reported	0
with	0
an	0
incidence	0
of	0
2	0
.	0
4	0
%	0
to	0
7	0
.	0
2	0
%	0
in	0
explanted	0
hearts	0
and	0
may	0
be	0
related	0
to	0
multidrug	0
therapy	0
.	0

Time	0
trends	0
in	0
warfarin	1
-	0
associated	0
hemorrhage	3
.	0

The	0
annual	0
incidence	0
of	0
warfarin	1
-	0
related	0
bleeding	3
at	0
Brigham	0
and	0
Women	0
'	0
s	0
Hospital	0
increased	0
from	0
0	0
.	0
97	0
/	0
1	0
,	0
000	0
patient	0
admissions	0
in	0
the	0
first	0
time	0
period	0
(	0
January	0
1995	0
to	0
0ctober	0
1998	0
)	0
to	0
1	0
.	0
19	0
/	0
1	0
,	0
000	0
patient	0
admissions	0
in	0
the	0
second	0
time	0
period	0
(	0
November	0
1998	0
to	0
August	0
2002	0
)	0
of	0
this	0
study	0
.	0

The	0
proportion	0
of	0
patients	0
with	0
major	0
and	0
intracranial	3
bleeding	4
increased	0
from	0
20	0
.	0
2	0
%	0
and	0
1	0
.	0
9	0
%	0
,	0
respectively	0
,	0
in	0
the	0
first	0
time	0
period	0
,	0
to	0
33	0
.	0
3	0
%	0
and	0
7	0
.	0
8	0
%	0
,	0
respectively	0
,	0
in	0
the	0
second	0
.	0

Yohimbine	1
treatment	0
of	0
sexual	3
side	4
effects	4
induced	0
by	0
serotonin	1
reuptake	0
blockers	0
.	0

BACKGR0UND	0
:	0
Preclinical	0
and	0
clinical	0
studies	0
suggest	0
that	0
yohimbine	1
facilitates	0
sexual	0
behavior	0
and	0
may	0
be	0
helpful	0
in	0
the	0
treatment	0
of	0
male	3
impotence	4
.	0

A	0
single	0
case	0
report	0
suggests	0
that	0
yohimbine	1
may	0
be	0
used	0
to	0
treat	0
the	0
sexual	3
side	4
effects	4
of	0
clomipramine	1
.	0

This	0
study	0
evaluated	0
yohimbine	1
as	0
a	0
treatment	0
for	0
the	0
sexual	3
side	4
effects	4
caused	0
by	0
serotonin	1
reuptake	0
blockers	0
.	0

METH0D	0
:	0
Six	0
patients	0
with	0
either	0
obsessive	3
compulsive	4
disorder	4
,	0
trichotillomania	3
,	0
anxiety	3
,	0
or	0
affective	3
disorders	4
who	0
suffered	0
sexual	3
side	4
effects	4
after	0
treatment	0
with	0
serotonin	1
reuptake	0
blockers	0
were	0
given	0
yohimbine	1
on	0
a	0
p	0
.	0
r	0
.	0
n	0
.	0
basis	0
in	0
an	0
open	0
clinical	0
trial	0
.	0

Various	0
doses	0
of	0
yohimbine	1
were	0
used	0
to	0
determine	0
the	0
ideal	0
dose	0
for	0
each	0
patient	0
.	0

RESULTS	0
:	0
Five	0
of	0
the	0
six	0
patients	0
experienced	0
improved	0
sexual	0
functioning	0
after	0
taking	0
yohimbine	1
.	0

0ne	0
patient	0
who	0
failed	0
to	0
comply	0
with	0
yohimbine	1
treatment	0
had	0
no	0
therapeutic	0
effects	0
.	0

Side	0
effects	0
of	0
yohimbine	1
included	0
excessive	0
sweating	0
,	0
increased	0
anxiety	3
,	0
and	0
a	0
wound	0
-	0
up	0
feeling	0
in	0
some	0
patients	0
.	0

C0NCLUSI0N	0
:	0
The	0
results	0
of	0
this	0
study	0
indicate	0
that	0
yohimbine	1
may	0
be	0
an	0
effective	0
treatment	0
for	0
the	0
sexual	3
side	4
effects	4
caused	0
by	0
serotonin	1
reuptake	0
blockers	0
.	0

Future	0
controlled	0
studies	0
are	0
needed	0
to	0
further	0
investigate	0
the	0
effectiveness	0
and	0
safety	0
of	0
yohimbine	1
for	0
this	0
indication	0
.	0

Hemorrhagic	3
cystitis	4
complicating	0
bone	0
marrow	0
transplantation	0
.	0

Hemorrhagic	3
cystitis	4
is	0
a	0
potentially	0
serious	0
complication	0
of	0
high	0
-	0
dose	0
cyclophosphamide	1
therapy	0
administered	0
before	0
bone	0
marrow	0
transplantation	0
.	0

As	0
standard	0
practice	0
at	0
our	0
institution	0
,	0
patients	0
who	0
are	0
scheduled	0
to	0
receive	0
a	0
bone	0
marrow	0
transplant	0
are	0
treated	0
prophylactically	0
with	0
forced	0
hydration	0
and	0
bladder	0
irrigation	0
.	0

In	0
an	0
attempt	0
to	0
obviate	0
the	0
inconvenience	0
of	0
bladder	0
irrigation	0
,	0
we	0
conducted	0
a	0
feasibility	0
trial	0
of	0
uroprophylaxis	0
with	0
mesna	1
,	0
which	0
neutralizes	0
the	0
hepatic	0
metabolite	0
of	0
cyclophosphamide	1
that	0
causes	0
hemorrhagic	3
cystitis	4
.	0

0f	0
97	0
patients	0
who	0
received	0
standard	0
prophylaxis	0
,	0
4	0
had	0
symptomatic	0
hemorrhagic	3
cystitis	4
.	0

In	0
contrast	0
,	0
two	0
of	0
four	0
consecutive	0
patients	0
who	0
received	0
mesna	1
uroprophylaxis	0
before	0
allogeneic	0
bone	0
marrow	0
transplantation	0
had	0
severe	0
hemorrhagic	3
cystitis	4
for	0
at	0
least	0
2	0
weeks	0
.	0

Because	0
of	0
this	0
suboptimal	0
result	0
,	0
we	0
resumed	0
the	0
use	0
of	0
bladder	0
irrigation	0
and	0
forced	0
hydration	0
to	0
minimize	0
the	0
risk	0
of	0
hemorrhagic	3
cystitis	4
.	0

Consensus	0
statement	0
concerning	0
cardiotoxicity	3
occurring	0
during	0
haematopoietic	0
stem	0
cell	0
transplantation	0
in	0
the	0
treatment	0
of	0
autoimmune	3
diseases	4
,	0
with	0
special	0
reference	0
to	0
systemic	3
sclerosis	4
and	0
multiple	3
sclerosis	4
.	0

Autologous	0
haematopoietic	0
stem	0
cell	0
transplantation	0
is	0
now	0
a	0
feasible	0
and	0
effective	0
treatment	0
for	0
selected	0
patients	0
with	0
severe	0
autoimmune	3
diseases	4
.	0

Worldwide	0
,	0
over	0
650	0
patients	0
have	0
been	0
transplanted	0
in	0
the	0
context	0
of	0
phase	0
I	0
and	0
II	0
clinical	0
trials	0
.	0

The	0
results	0
are	0
encouraging	0
enough	0
to	0
begin	0
randomised	0
phase	0
III	0
trials	0
.	0

However	0
,	0
as	0
predicted	0
,	0
significant	0
transplant	0
-	0
related	0
morbidity	0
and	0
mortality	0
have	0
been	0
observed	0
.	0

This	0
is	0
primarily	0
due	0
to	0
complications	0
related	0
to	0
either	0
the	0
stage	0
of	0
the	0
disease	0
at	0
transplant	0
or	0
due	0
to	0
infections	3
.	0

The	0
number	0
of	0
deaths	0
related	0
to	0
cardiac	3
toxicity	4
is	0
low	0
.	0

However	0
,	0
caution	0
is	0
required	0
when	0
cyclophosphamide	1
or	0
anthracyclines	1
such	0
as	0
mitoxantrone	1
are	0
used	0
in	0
patients	0
with	0
a	0
possible	0
underlying	0
heart	3
damage	4
,	0
for	0
example	0
,	0
systemic	3
sclerosis	4
patients	0
.	0

In	0
November	0
2002	0
,	0
a	0
meeting	0
was	0
held	0
in	0
Florence	0
,	0
bringing	0
together	0
a	0
number	0
of	0
experts	0
in	0
various	0
fields	0
,	0
including	0
rheumatology	0
,	0
cardiology	0
,	0
neurology	0
,	0
pharmacology	0
and	0
transplantation	0
medicine	0
.	0

The	0
object	0
of	0
the	0
meeting	0
was	0
to	0
analyse	0
existing	0
data	0
,	0
both	0
published	0
or	0
available	0
,	0
in	0
the	0
European	0
Group	0
for	0
Blood	0
and	0
Marrow	0
Transplantation	0
autoimmune	3
disease	4
database	0
,	0
and	0
to	0
propose	0
a	0
safe	0
approach	0
to	0
such	0
patients	0
.	0

A	0
full	0
cardiological	0
assessment	0
before	0
and	0
during	0
the	0
transplant	0
emerged	0
as	0
the	0
major	0
recommendation	0
.	0

Does	0
supplemental	0
vitamin	1
C	2
increase	0
cardiovascular	3
disease	4
risk	0
in	0
women	0
with	0
diabetes	3
?	0

BACKGR0UND	0
:	0
Vitamin	1
C	2
acts	0
as	0
a	0
potent	0
antioxidant	0
;	0
however	0
,	0
it	0
can	0
also	0
be	0
a	0
prooxidant	0
and	0
glycate	0
protein	0
under	0
certain	0
circumstances	0
in	0
vitro	0
.	0

These	0
observations	0
led	0
us	0
to	0
hypothesize	0
that	0
a	0
high	0
intake	0
of	0
vitamin	1
C	2
in	0
diabetic	3
persons	0
might	0
promote	0
atherosclerosis	3
.	0

0BJECTIVE	0
:	0
The	0
objective	0
was	0
to	0
examine	0
the	0
relation	0
between	0
vitamin	1
C	2
intake	0
and	0
mortality	0
from	0
cardiovascular	3
disease	4
.	0

DESIGN	0
:	0
We	0
studied	0
the	0
relation	0
between	0
vitamin	1
C	2
intake	0
and	0
mortality	0
from	0
total	0
cardiovascular	3
disease	4
(	0
n	0
=	0
281	0
)	0
,	0
coronary	3
artery	4
disease	4
(	0
n	0
=	0
175	0
)	0
,	0
and	0
stroke	3
(	0
n	0
=	0
57	0
)	0
in	0
1923	0
postmenopausal	0
women	0
who	0
reported	0
being	0
diabetic	3
at	0
baseline	0
.	0

Diet	0
was	0
assessed	0
with	0
a	0
food	0
-	0
frequency	0
questionnaire	0
at	0
baseline	0
,	0
and	0
subjects	0
initially	0
free	0
of	0
coronary	3
artery	4
disease	4
were	0
prospectively	0
followed	0
for	0
15	0
y	0
.	0

RESULTS	0
:	0
After	0
adjustment	0
for	0
cardiovascular	3
disease	4
risk	0
factors	0
,	0
type	0
of	0
diabetes	3
medication	0
used	0
,	0
duration	0
of	0
diabetes	3
,	0
and	0
intakes	0
of	0
folate	1
,	0
vitamin	1
E	2
,	0
and	0
beta	1
-	2
carotene	2
,	0
the	0
adjusted	0
relative	0
risks	0
of	0
total	0
cardiovascular	3
disease	4
mortality	0
were	0
1	0
.	0
0	0
,	0
0	0
.	0
97	0
,	0
1	0
.	0
11	0
,	0
1	0
.	0
47	0
,	0
and	0
1	0
.	0
84	0
(	0
P	0
for	0
trend	0
<	0
0	0
.	0
01	0
)	0
across	0
quintiles	0
of	0
total	0
vitamin	1
C	2
intake	0
from	0
food	0
and	0
supplements	0
.	0

Adjusted	0
relative	0
risks	0
of	0
coronary	3
artery	4
disease	4
were	0
1	0
.	0
0	0
,	0
0	0
.	0
81	0
,	0
0	0
.	0
99	0
,	0
1	0
.	0
26	0
,	0
and	0
1	0
.	0
91	0
(	0
P	0
for	0
trend	0
=	0
0	0
.	0
01	0
)	0
and	0
of	0
stroke	3
were	0
1	0
.	0
0	0
,	0
0	0
.	0
52	0
,	0
1	0
.	0
23	0
,	0
2	0
.	0
22	0
,	0
and	0
2	0
.	0
57	0
(	0
P	0
for	0
trend	0
<	0
0	0
.	0
01	0
)	0
.	0

When	0
dietary	0
and	0
supplemental	0
vitamin	1
C	2
were	0
analyzed	0
separately	0
,	0
only	0
supplemental	0
vitamin	1
C	2
showed	0
a	0
positive	0
association	0
with	0
mortality	0
endpoints	0
.	0

Vitamin	1
C	2
intake	0
was	0
unrelated	0
to	0
mortality	0
from	0
cardiovascular	3
disease	4
in	0
the	0
nondiabetic	0
subjects	0
at	0
baseline	0
.	0

C0NCLUSI0N	0
:	0
A	0
high	0
vitamin	1
C	2
intake	0
from	0
supplements	0
is	0
associated	0
with	0
an	0
increased	0
risk	0
of	0
cardiovascular	3
disease	4
mortality	0
in	0
postmenopausal	0
women	0
with	0
diabetes	3
.	0

0ptical	0
coherence	0
tomography	0
can	0
measure	0
axonal	0
loss	0
in	0
patients	0
with	0
ethambutol	1
-	0
induced	0
optic	3
neuropathy	4
.	0

PURP0SE	0
:	0
To	0
map	0
and	0
identify	0
the	0
pattern	0
,	0
in	0
vivo	0
,	0
of	0
axonal	3
degeneration	4
in	0
ethambutol	1
-	0
induced	0
optic	3
neuropathy	4
using	0
optical	0
coherence	0
tomography	0
(	0
0CT	0
)	0
.	0

Ethambutol	1
is	0
an	0
antimycobacterial	0
agent	0
often	0
used	0
to	0
treat	0
tuberculosis	3
.	0

A	0
serious	0
complication	0
of	0
ethambutol	1
is	0
an	0
optic	3
neuropathy	4
that	0
impairs	0
visual	0
acuity	0
,	0
contrast	0
sensitivity	0
,	0
and	0
color	0
vision	0
.	0

However	0
,	0
early	0
on	0
,	0
when	0
the	0
toxic	0
optic	3
neuropathy	4
is	0
mild	0
and	0
partly	0
reversible	0
,	0
the	0
funduscopic	0
findings	0
are	0
often	0
subtle	0
and	0
easy	0
to	0
miss	0
.	0

METH0DS	0
:	0
Three	0
subjects	0
with	0
a	0
history	0
of	0
ethambutol	1
(	0
EMB	1
)	0
-	0
induced	0
optic	3
neuropathy	4
of	0
short	0
-	0
,	0
intermediate	0
-	0
,	0
and	0
long	0
-	0
term	0
visual	3
deficits	4
were	0
administered	0
a	0
full	0
neuro	0
-	0
ophthalmologic	0
examination	0
including	0
visual	0
acuity	0
,	0
color	0
vision	0
,	0
contrast	0
sensitivity	0
,	0
and	0
fundus	0
examination	0
.	0

In	0
addition	0
,	0
0CT	0
(	0
0CT	0
3000	0
,	0
Humphrey	0
-	0
Zeiss	0
,	0
Dublin	0
,	0
CA	0
)	0
was	0
performed	0
on	0
both	0
eyes	0
of	0
each	0
subject	0
using	0
the	0
retinal	0
nerve	0
fiber	0
layer	0
(	0
RNFL	0
)	0
analysis	0
protocol	0
.	0

0CT	0
interpolates	0
data	0
from	0
100	0
points	0
around	0
the	0
optic	0
nerve	0
to	0
effectively	0
map	0
out	0
the	0
RNFL	0
.	0

RESULTS	0
:	0
The	0
results	0
were	0
compared	0
to	0
the	0
calculated	0
average	0
RNFL	0
of	0
normal	0
eyes	0
accumulated	0
from	0
four	0
prior	0
studies	0
using	0
0CT	0
,	0
n	0
=	0
661	0
.	0

In	0
all	0
subjects	0
with	0
history	0
of	0
EMB	1
-	0
induced	0
optic	3
neuropathy	4
,	0
there	0
was	0
a	0
mean	0
loss	0
of	0
72	0
%	0
nerve	0
fiber	0
layer	0
thickness	0
in	0
the	0
temporal	0
quadrant	0
(	0
patient	0
A	0
,	0
with	0
eventual	0
recovery	0
of	0
visual	0
acuity	0
and	0
fields	0
,	0
58	0
%	0
loss	0
;	0
patient	0
B	0
,	0
with	0
intermediate	0
visual	3
deficits	4
,	0
68	0
%	0
loss	0
;	0
patient	0
C	0
,	0
with	0
chronic	0
visual	3
deficits	4
,	0
90	0
%	0
loss	0
)	0
,	0
with	0
an	0
average	0
mean	0
optic	0
nerve	0
thickness	0
of	0
26	0
+	0
/	0
-	0
16	0
microm	0
.	0

There	0
was	0
a	0
combined	0
mean	0
loss	0
of	0
46	0
%	0
of	0
fibers	0
from	0
the	0
superior	0
,	0
inferior	0
,	0
and	0
nasal	0
quadrants	0
in	0
the	0
(	0
six	0
)	0
eyes	0
of	0
all	0
three	0
subjects	0
(	0
mean	0
average	0
thickness	0
of	0
55	0
+	0
/	0
-	0
29	0
microm	0
)	0
.	0

In	0
both	0
sets	0
(	0
four	0
)	0
of	0
eyes	0
of	0
the	0
subjects	0
with	0
persistent	0
visual	3
deficits	4
(	0
patients	0
B	0
and	0
C	0
)	0
,	0
there	0
was	0
an	0
average	0
loss	0
of	0
79	0
%	0
of	0
nerve	0
fiber	0
thickness	0
in	0
the	0
temporal	0
quadrant	0
.	0

C0NCLUSI0NS	0
:	0
The	0
0CT	0
results	0
in	0
these	0
patients	0
with	0
EMB	1
-	0
induced	0
optic	3
neuropathy	4
show	0
considerable	0
loss	0
especially	0
of	0
the	0
temporal	0
fibers	0
.	0

This	0
is	0
consistent	0
with	0
prior	0
histopathological	0
studies	0
that	0
show	0
predominant	0
loss	0
of	0
parvo	0
-	0
cellular	0
axons	0
(	0
or	0
small	0
-	0
caliber	0
axons	0
)	0
within	0
the	0
papillo	0
-	0
macular	0
bundle	0
in	0
toxic	0
or	0
hereditary	0
optic	3
neuropathies	4
.	0

0CT	0
can	0
be	0
a	0
valuable	0
tool	0
in	0
the	0
quantitative	0
analysis	0
of	0
optic	3
neuropathies	4
.	0

Additionally	0
,	0
in	0
terms	0
of	0
management	0
of	0
EMB	1
-	0
induced	0
optic	3
neuropathy	4
,	0
it	0
is	0
important	0
to	0
properly	0
manage	0
ethambutol	1
dosing	0
in	0
patients	0
with	0
renal	3
impairment	4
and	0
to	0
achieve	0
proper	0
transition	0
to	0
a	0
maintenance	0
dose	0
once	0
an	0
appropriate	0
loading	0
dose	0
has	0
been	0
reached	0
.	0

Hypoxia	3
in	0
renal	3
disease	4
with	0
proteinuria	3
and	0
/	0
or	0
glomerular	0
hypertension	3
.	0

Despite	0
the	0
increasing	0
need	0
to	0
identify	0
and	0
quantify	0
tissue	0
oxygenation	0
at	0
the	0
cellular	0
level	0
,	0
relatively	0
few	0
methods	0
have	0
been	0
available	0
.	0

In	0
this	0
study	0
,	0
we	0
developed	0
a	0
new	0
hypoxia	3
-	0
responsive	0
reporter	0
vector	0
using	0
a	0
hypoxia	3
-	0
responsive	0
element	0
of	0
the	0
5	0
'	0
vascular	0
endothelial	0
growth	0
factor	0
untranslated	0
region	0
and	0
generated	0
a	0
novel	0
hypoxia	3
-	0
sensing	0
transgenic	0
rat	0
.	0

We	0
then	0
applied	0
this	0
animal	0
model	0
to	0
the	0
detection	0
of	0
tubulointerstitial	0
hypoxia	3
in	0
the	0
diseased	3
kidney	4
.	0

With	0
this	0
model	0
,	0
we	0
were	0
able	0
to	0
identify	0
diffuse	0
cortical	0
hypoxia	3
in	0
the	0
puromycin	1
aminonucleoside	2
-	0
induced	0
nephrotic	3
syndrome	4
and	0
focal	0
and	0
segmental	0
hypoxia	3
in	0
the	0
remnant	0
kidney	0
model	0
.	0

Expression	0
of	0
the	0
hypoxia	3
-	0
responsive	0
transgene	0
increased	0
throughout	0
the	0
observation	0
period	0
,	0
reaching	0
2	0
.	0
2	0
-	0
fold	0
at	0
2	0
weeks	0
in	0
the	0
puromycin	1
aminonucleoside	2
model	0
and	0
2	0
.	0
6	0
-	0
fold	0
at	0
4	0
weeks	0
in	0
the	0
remnant	0
kidney	0
model	0
,	0
whereas	0
that	0
of	0
vascular	0
endothelial	0
growth	0
factor	0
showed	0
a	0
mild	0
decrease	0
,	0
reflecting	0
distinct	0
behaviors	0
of	0
the	0
two	0
genes	0
.	0

The	0
degree	0
of	0
hypoxia	3
showed	0
a	0
positive	0
correlation	0
with	0
microscopic	0
tubulointerstitial	3
injury	4
in	0
both	0
models	0
.	0

Finally	0
,	0
we	0
identified	0
the	0
localization	0
of	0
proliferating	0
cell	0
nuclear	0
antigen	0
-	0
positive	0
,	0
ED	0
-	0
1	0
-	0
positive	0
,	0
and	0
terminal	0
dUTP	0
nick	0
-	0
end	0
labeled	0
-	0
positive	0
cells	0
in	0
the	0
hypoxic	3
cortical	0
area	0
in	0
the	0
remnant	0
kidney	0
model	0
.	0

We	0
propose	0
here	0
a	0
possible	0
pathological	0
tie	0
between	0
chronic	0
tubulointerstitial	0
hypoxia	3
and	0
progressive	0
glomerular	3
diseases	4
.	0

Adequate	0
timing	0
of	0
ribavirin	1
reduction	0
in	0
patients	0
with	0
hemolysis	3
during	0
combination	0
therapy	0
of	0
interferon	1
and	0
ribavirin	1
for	0
chronic	3
hepatitis	4
C	4
.	0

BACKGR0UND	0
:	0
Hemolytic	3
anemia	4
is	0
one	0
of	0
the	0
major	0
adverse	0
events	0
of	0
the	0
combination	0
therapy	0
of	0
interferon	1
and	0
ribavirin	1
.	0

Because	0
of	0
ribavirin	1
-	0
related	0
hemolytic	3
anemia	4
,	0
dose	0
reduction	0
is	0
a	0
common	0
event	0
in	0
this	0
therapy	0
.	0

In	0
this	0
clinical	0
retrospective	0
cohort	0
study	0
we	0
have	0
examined	0
the	0
suitable	0
timing	0
of	0
ribavirin	1
reduction	0
in	0
patients	0
with	0
hemolysis	3
during	0
combination	0
therapy	0
.	0

METH0DS	0
:	0
Thirty	0
-	0
seven	0
of	0
160	0
patients	0
who	0
had	0
HCV	0
-	0
genotype	0
1b	0
,	0
had	0
high	0
virus	0
load	0
,	0
and	0
received	0
24	0
-	0
week	0
combination	0
therapy	0
developed	0
anemia	3
with	0
hemoglobin	0
level	0
<	0
10	0
g	0
/	0
dl	0
or	0
anemia	3
-	0
related	0
signs	0
during	0
therapy	0
.	0

After	0
that	0
,	0
these	0
37	0
patients	0
were	0
reduced	0
one	0
tablet	0
of	0
ribavirin	1
(	0
200	0
mg	0
)	0
per	0
day	0
.	0

After	0
reduction	0
of	0
ribavirin	1
,	0
27	0
of	0
37	0
patients	0
could	0
continue	0
combination	0
therapy	0
for	0
a	0
total	0
of	0
24	0
weeks	0
(	0
group	0
A	0
)	0
.	0

However	0
,	0
10	0
of	0
37	0
patients	0
with	0
reduction	0
of	0
ribavirin	1
could	0
not	0
continue	0
combination	0
therapy	0
because	0
their	0
<	0
8	0
.	0
5	0
g	0
/	0
dl	0
hemoglobin	0
values	0
decreased	0
to	0
or	0
anemia	3
-	0
related	0
severe	0
side	0
effects	0
occurred	0
(	0
group	0
B	0
)	0
.	0

We	0
assessed	0
the	0
final	0
efficacy	0
and	0
safety	0
after	0
reduction	0
of	0
ribavirin	1
in	0
groups	0
A	0
and	0
B	0
.	0

RESULTS	0
:	0
A	0
sustained	0
virological	0
response	0
(	0
SVR	0
)	0
was	0
29	0
.	0
6	0
%	0
(	0
8	0
/	0
27	0
)	0
in	0
group	0
A	0
and	0
10	0
%	0
(	0
1	0
/	0
10	0
)	0
in	0
group	0
B	0
,	0
respectively	0
.	0

A	0
34	0
.	0
4	0
%	0
(	0
12	0
/	0
27	0
)	0
of	0
SVR	0
+	0
biological	0
response	0
in	0
group	0
A	0
was	0
higher	0
than	0
10	0
%	0
(	0
1	0
/	0
10	0
)	0
in	0
group	0
B	0
(	0
P	0
=	0
0	0
.	0
051	0
)	0
,	0
with	0
slight	0
significance	0
.	0

With	0
respect	0
to	0
hemoglobin	0
level	0
at	0
the	0
time	0
of	0
ribavirin	1
reduction	0
,	0
a	0
rate	0
of	0
continuation	0
of	0
therapy	0
in	0
patients	0
with	0
>	0
or	0
=	0
10	0
g	0
/	0
dl	0
hemoglobin	0
was	0
higher	0
than	0
that	0
in	0
patients	0
with	0
<	0
10	0
g	0
/	0
dl	0
(	0
P	0
=	0
0	0
.	0
036	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Reduction	0
of	0
ribavirin	1
at	0
hemoglobin	0
level	0
>	0
or	0
=	0
10	0
g	0
/	0
dl	0
is	0
suitable	0
in	0
terms	0
of	0
efficacy	0
and	0
side	0
effects	0
.	0

Aging	0
process	0
of	0
epithelial	0
cells	0
of	0
the	0
rat	0
prostate	0
lateral	0
lobe	0
in	0
experimental	0
hyperprolactinemia	3
induced	0
by	0
haloperidol	1
.	0

The	0
aim	0
of	0
the	0
study	0
was	0
to	0
examine	0
the	0
influence	0
of	0
hyperprolactinemia	3
,	0
induced	0
by	0
haloperidol	1
(	0
HAL	1
)	0
on	0
age	0
related	0
morphology	0
and	0
function	0
changes	0
of	0
epithelial	0
cells	0
in	0
rat	0
prostate	0
lateral	0
lobe	0
.	0

The	0
study	0
was	0
performed	0
on	0
sexually	0
mature	0
male	0
rats	0
.	0

Serum	0
concentrations	0
of	0
prolactin	0
(	0
PRL	1
)	0
and	0
testosterone	1
(	0
T	1
)	0
were	0
measured	0
.	0

Tissue	0
sections	0
were	0
evaluated	0
with	0
light	0
and	0
electron	0
microscopy	0
.	0

Immunohistochemical	0
reactions	0
for	0
Anti	0
-	0
Proliferating	0
Cell	0
Nuclear	0
Antigen	0
(	0
PCNA	0
)	0
were	0
performed	0
.	0

In	0
rats	0
of	0
the	0
experimental	0
group	0
,	0
the	0
mean	0
concentration	0
of	0
:	0
PRL	1
was	0
more	0
than	0
twice	0
higher	0
,	0
whereas	0
T	1
concentration	0
was	0
almost	0
twice	0
lower	0
than	0
that	0
in	0
the	0
control	0
group	0
.	0

Light	0
microscopy	0
visualized	0
the	0
following	0
:	0
hypertrophy	3
and	0
epithelium	0
hyperplasia	3
of	0
the	0
glandular	0
ducts	0
,	0
associated	0
with	0
increased	0
PCNA	0
expression	0
.	0

Electron	0
microscopy	0
revealed	0
changes	0
in	0
columnar	0
epithelial	0
cells	0
,	0
concerning	0
organelles	0
,	0
engaged	0
in	0
protein	0
synthesis	0
and	0
secretion	0
.	0

Relation	0
of	0
perfusion	0
defects	0
observed	0
with	0
myocardial	0
contrast	0
echocardiography	0
to	0
the	0
severity	0
of	0
coronary	3
stenosis	4
:	0
correlation	0
with	0
thallium	1
-	0
201	0
single	0
-	0
photon	0
emission	0
tomography	0
.	0

It	0
has	0
been	0
previously	0
shown	0
that	0
myocardial	0
contrast	0
echocardiography	0
is	0
a	0
valuable	0
technique	0
for	0
delineating	0
regions	0
of	0
myocardial	0
underperfusion	0
secondary	0
to	0
coronary	3
occlusion	4
and	0
to	0
critical	0
coronary	3
stenoses	4
in	0
the	0
presence	0
of	0
hyperemic	3
stimulation	0
.	0

The	0
aim	0
of	0
this	0
study	0
was	0
to	0
determine	0
whether	0
myocardial	0
contrast	0
echocardiography	0
performed	0
with	0
a	0
stable	0
solution	0
of	0
sonicated	0
albumin	0
could	0
detect	0
regions	0
of	0
myocardial	0
underperfusion	0
resulting	0
from	0
various	0
degrees	0
of	0
coronary	3
stenosis	4
.	0

The	0
perfusion	0
defect	0
produced	0
in	0
16	0
open	0
chest	0
dogs	0
was	0
compared	0
with	0
the	0
anatomic	0
area	0
at	0
risk	0
measured	0
by	0
the	0
postmortem	0
dual	0
-	0
perfusion	0
technique	0
and	0
with	0
thallium	1
-	0
201	0
single	0
-	0
photon	0
emission	0
tomography	0
(	0
SPECT	0
)	0
.	0

During	0
a	0
transient	0
(	0
20	0
-	0
s	0
)	0
coronary	3
occlusion	4
,	0
a	0
perfusion	0
defect	0
was	0
observed	0
with	0
contrast	0
echocardiography	0
in	0
14	0
of	0
the	0
15	0
dogs	0
in	0
which	0
the	0
occlusion	0
was	0
produced	0
.	0

The	0
perfusion	0
defect	0
correlated	0
significantly	0
with	0
the	0
anatomic	0
area	0
at	0
risk	0
(	0
r	0
=	0
0	0
.	0
74	0
;	0
p	0
less	0
than	0
0	0
.	0
002	0
)	0
.	0

During	0
dipyridamole	1
-	0
induced	0
hyperemia	3
,	0
12	0
of	0
the	0
16	0
dogs	0
with	0
a	0
partial	0
coronary	3
stenosis	4
had	0
a	0
visible	0
area	0
of	0
hypoperfusion	0
by	0
contrast	0
echocardiography	0
.	0

The	0
four	0
dogs	0
without	0
a	0
perfusion	0
defect	0
had	0
a	0
stenosis	0
that	0
resulted	0
in	0
a	0
mild	0
(	0
0	0
%	0
to	0
50	0
%	0
)	0
reduction	0
in	0
dipyridamole	1
-	0
induced	0
hyperemia	3
.	0

The	0
size	0
of	0
the	0
perfusion	0
defect	0
during	0
stenosis	0
correlated	0
significantly	0
with	0
the	0
anatomic	0
area	0
at	0
risk	0
(	0
r	0
=	0
0	0
.	0
61	0
;	0
p	0
=	0
0	0
.	0
02	0
)	0
.	0

Thallium	1
-	0
201	0
SPECT	0
demonstrated	0
a	0
perfusion	0
defect	0
in	0
all	0
14	0
dogs	0
analyzed	0
during	0
dipyridamole	1
-	0
induced	0
hyperemia	3
;	0
the	0
size	0
of	0
the	0
perfusion	0
defect	0
correlated	0
with	0
the	0
anatomic	0
area	0
at	0
risk	0
(	0
r	0
=	0
0	0
.	0
58	0
;	0
p	0
less	0
than	0
0	0
.	0
03	0
)	0
and	0
with	0
the	0
perfusion	0
defect	0
by	0
contrast	0
echocardiography	0
(	0
r	0
=	0
0	0
.	0
58	0
;	0
p	0
less	0
than	0
0	0
.	0
03	0
)	0
.	0

Thus	0
,	0
myocardial	0
contrast	0
echocardiography	0
can	0
be	0
used	0
to	0
visualize	0
and	0
quantitate	0
the	0
amount	0
of	0
jeopardized	0
myocardium	0
during	0
moderate	0
to	0
severe	0
degrees	0
of	0
coronary	3
stenosis	4
.	0

The	0
results	0
obtained	0
show	0
a	0
correlation	0
with	0
the	0
anatomic	0
area	0
at	0
risk	0
similar	0
to	0
that	0
obtained	0
with	0
thallium	1
-	0
201	0
SPECT	0
.	0

The	0
activation	0
of	0
spinal	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
receptors	0
may	0
contribute	0
to	0
degeneration	0
of	0
spinal	0
motor	0
neurons	0
induced	0
by	0
neuraxial	0
morphine	1
after	0
a	0
noninjurious	0
interval	0
of	0
spinal	3
cord	4
ischemia	4
.	0

We	0
investigated	0
the	0
relationship	0
between	0
the	0
degeneration	0
of	0
spinal	0
motor	0
neurons	0
and	0
activation	0
of	0
N	1
-	2
methyl	2
-	2
d	2
-	2
aspartate	2
(	0
NMDA	1
)	0
receptors	0
after	0
neuraxial	0
morphine	1
following	0
a	0
noninjurious	0
interval	0
of	0
aortic	3
occlusion	4
in	0
rats	0
.	0

Spinal	3
cord	4
ischemia	4
was	0
induced	0
by	0
aortic	3
occlusion	4
for	0
6	0
min	0
with	0
a	0
balloon	0
catheter	0
.	0

In	0
a	0
microdialysis	0
study	0
,	0
10	0
muL	0
of	0
saline	0
(	0
group	0
C	0
;	0
n	0
=	0
8	0
)	0
or	0
30	0
mug	0
of	0
morphine	1
(	0
group	0
M	0
;	0
n	0
=	0
8	0
)	0
was	0
injected	0
intrathecally	0
(	0
IT	0
)	0
0	0
.	0
5	0
h	0
after	0
reflow	0
,	0
and	0
30	0
mug	0
of	0
morphine	1
(	0
group	0
SM	0
;	0
n	0
=	0
8	0
)	0
or	0
10	0
muL	0
of	0
saline	0
(	0
group	0
SC	0
;	0
n	0
=	0
8	0
)	0
was	0
injected	0
IT	0
0	0
.	0
5	0
h	0
after	0
sham	0
operation	0
.	0

Microdialysis	0
samples	0
were	0
collected	0
preischemia	0
,	0
before	0
IT	0
injection	0
,	0
and	0
at	0
2	0
,	0
4	0
,	0
8	0
,	0
24	0
,	0
and	0
48	0
h	0
of	0
reperfusion	0
(	0
after	0
IT	0
injection	0
)	0
.	0

Second	0
,	0
we	0
investigated	0
the	0
effect	0
of	0
IT	0
MK	1
-	2
801	2
(	0
30	0
mug	0
)	0
on	0
the	0
histopathologic	0
changes	0
in	0
the	0
spinal	0
cord	0
after	0
morphine	1
-	0
induced	0
spastic	3
paraparesis	4
.	0

After	0
IT	0
morphine	1
,	0
the	0
cerebrospinal	0
fluid	0
(	0
CSF	0
)	0
glutamate	1
concentration	0
was	0
increased	0
in	0
group	0
M	0
relative	0
to	0
both	0
baseline	0
and	0
group	0
C	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

This	0
increase	0
persisted	0
for	0
8	0
hrs	0
.	0

IT	0
MK	1
-	2
801	2
significantly	0
reduced	0
the	0
number	0
of	0
dark	0
-	0
stained	0
alpha	0
-	0
motoneurons	0
after	0
morphine	1
-	0
induced	0
spastic	3
paraparesis	4
compared	0
with	0
the	0
saline	0
group	0
.	0

These	0
data	0
indicate	0
that	0
IT	0
morphine	1
induces	0
spastic	3
paraparesis	4
with	0
a	0
concomitant	0
increase	0
in	0
CSF	0
glutamate	1
,	0
which	0
is	0
involved	0
in	0
NMDA	1
receptor	0
activation	0
.	0

We	0
suggest	0
that	0
opioids	0
may	0
be	0
neurotoxic	3
in	0
the	0
setting	0
of	0
spinal	3
cord	4
ischemia	4
via	0
NMDA	1
receptor	0
activation	0
.	0

Acute	0
low	3
back	4
pain	4
during	0
intravenous	0
administration	0
of	0
amiodarone	1
:	0
a	0
report	0
of	0
two	0
cases	0
.	0

Amiodarone	1
represents	0
an	0
effective	0
antiarrhythmic	0
drug	0
for	0
cardioversion	0
of	0
recent	0
-	0
onset	0
atrial	3
fibrillation	4
(	0
AF	3
)	0
and	0
maintenance	0
of	0
sinus	0
rhythm	0
.	0

We	0
briefly	0
describe	0
two	0
patients	0
suffering	0
from	0
recent	0
-	0
onset	0
atrial	3
fibrillation	4
,	0
who	0
experienced	0
an	0
acute	0
devastating	0
low	3
back	4
pain	4
a	0
few	0
minutes	0
after	0
initiation	0
of	0
intravenous	0
amiodarone	1
loading	0
.	0

Notably	0
,	0
this	0
side	0
effect	0
has	0
not	0
been	0
ever	0
reported	0
in	0
the	0
medical	0
literature	0
.	0

Clinicians	0
should	0
be	0
aware	0
of	0
this	0
reaction	0
since	0
prompt	0
termination	0
of	0
parenteral	0
administration	0
leads	0
to	0
complete	0
resolution	0
.	0

Quantitative	0
drug	0
levels	0
in	0
stimulant	0
psychosis	3
:	0
relationship	0
to	0
symptom	0
severity	0
,	0
catecholamines	1
and	0
hyperkinesia	3
.	0

To	0
examine	0
the	0
relationship	0
between	0
quantitative	0
stimulant	0
drug	0
levels	0
,	0
catecholamines	1
,	0
and	0
psychotic	3
symptoms	4
,	0
nineteen	0
patients	0
in	0
a	0
psychiatric	3
emergency	0
service	0
with	0
a	0
diagnosis	0
of	0
amphetamine	1
-	0
or	0
cocaine	1
-	0
induced	0
psychosis	3
were	0
interviewed	0
,	0
and	0
plasma	0
and	0
urine	0
were	0
collected	0
for	0
quantitative	0
assays	0
of	0
stimulant	0
drug	0
and	0
catecholamine	1
metabolite	0
levels	0
.	0

Methamphetamine	1
or	0
amphetamine	1
levels	0
were	0
related	0
to	0
several	0
psychopathology	0
scores	0
and	0
the	0
global	0
hyperkinesia	3
rating	0
.	0

HVA	0
levels	0
were	0
related	0
to	0
global	0
hyperkinesia	3
but	0
not	0
to	0
psychopathology	0
ratings	0
.	0

Although	0
many	0
other	0
factors	0
such	0
as	0
sensitization	0
may	0
play	0
a	0
role	0
,	0
intensity	0
of	0
stimulant	0
-	0
induced	0
psychotic	3
symptoms	4
and	0
stereotypies	3
appears	0
to	0
be	0
at	0
least	0
in	0
part	0
dose	0
-	0
related	0
.	0

Pheochromocytoma	3
unmasked	0
by	0
amisulpride	1
and	0
tiapride	1
.	0

0BJECTIVE	0
:	0
To	0
describe	0
the	0
unmasking	0
of	0
pheochromocytoma	3
in	0
a	0
patient	0
treated	0
with	0
amisulpride	1
and	0
tiapride	1
.	0

CASE	0
SUMMARY	0
:	0
A	0
42	0
-	0
year	0
-	0
old	0
white	0
man	0
developed	0
acute	0
hypertension	3
with	0
severe	0
headache	3
and	0
vomiting	3
2	0
hours	0
after	0
the	0
first	0
doses	0
of	0
amisulpride	1
100	0
mg	0
and	0
tiapride	1
100	0
mg	0
.	0

Both	0
drugs	0
were	0
immediately	0
discontinued	0
,	0
and	0
the	0
patient	0
recovered	0
after	0
subsequent	0
nicardipine	1
and	0
verapamil	1
treatment	0
.	0

Abdominal	0
ultrasound	0
showed	0
an	0
adrenal	0
mass	0
,	0
and	0
postoperative	0
histologic	0
examination	0
confirmed	0
the	0
diagnosis	0
of	0
pheochromocytoma	3
.	0

DISCUSSI0N	0
:	0
Drug	0
-	0
induced	0
symptoms	0
of	0
pheochromocytoma	3
are	0
often	0
associated	0
with	0
the	0
use	0
of	0
substituted	0
benzamide	1
drugs	0
,	0
but	0
the	0
underlying	0
mechanism	0
is	0
unknown	0
.	0

In	0
our	0
case	0
,	0
use	0
of	0
the	0
Naranjo	0
probability	0
scale	0
indicated	0
a	0
possible	0
relationship	0
between	0
the	0
hypertensive	3
crisis	0
and	0
amisulpride	1
and	0
tiapride	1
therapy	0
.	0

C0NCLUSI0NS	0
:	0
As	0
of	0
March	0
24	0
,	0
2005	0
,	0
this	0
is	0
the	0
first	0
reported	0
case	0
of	0
amisulpride	1
-	0
and	0
tiapride	1
-	0
induced	0
hypertensive	3
crisis	0
in	0
a	0
patient	0
with	0
pheochromocytoma	3
.	0

Physicians	0
and	0
other	0
healthcare	0
professionals	0
should	0
be	0
aware	0
of	0
this	0
potential	0
adverse	0
effect	0
of	0
tiapride	1
and	0
amisulpride	1
.	0

Minor	0
neurological	3
dysfunction	4
,	0
cognitive	0
development	0
,	0
and	0
somatic	0
development	0
at	0
the	0
age	0
of	0
3	0
to	0
7	0
years	0
after	0
dexamethasone	1
treatment	0
in	0
very	0
-	0
low	0
birth	0
-	0
weight	0
infants	0
.	0

The	0
objective	0
of	0
this	0
study	0
was	0
to	0
assess	0
minor	0
neurological	3
dysfunction	4
,	0
cognitive	0
development	0
,	0
and	0
somatic	0
development	0
after	0
dexamethasone	1
therapy	0
in	0
very	0
-	0
low	0
-	0
birthweight	0
infants	0
.	0

Thirty	0
-	0
three	0
children	0
after	0
dexamethasone	1
treatment	0
were	0
matched	0
to	0
33	0
children	0
without	0
dexamethasone	1
treatment	0
.	0

Data	0
were	0
assessed	0
at	0
the	0
age	0
of	0
3	0
-	0
7	0
years	0
.	0

Dexamethasone	1
was	0
started	0
between	0
the	0
7th	0
and	0
the	0
28th	0
day	0
of	0
life	0
over	0
7	0
days	0
with	0
a	0
total	0
dose	0
of	0
2	0
.	0
35	0
mg	0
/	0
kg	0
/	0
day	0
.	0

Exclusion	0
criteria	0
were	0
asphyxia	3
,	0
malformations	3
,	0
major	0
surgical	0
interventions	0
,	0
small	0
for	0
gestational	0
age	0
,	0
intraventricular	0
haemorrhage	3
grades	0
III	0
and	0
IV	0
,	0
periventricular	3
leukomalacia	4
,	0
and	0
severe	0
psychomotor	3
retardation	4
.	0

Each	0
child	0
was	0
examined	0
by	0
a	0
neuropediatrician	0
for	0
minor	0
neurological	3
dysfunctions	4
and	0
tested	0
by	0
a	0
psychologist	0
for	0
cognitive	0
development	0
with	0
a	0
Kaufman	0
Assessment	0
Battery	0
for	0
Children	0
and	0
a	0
Draw	0
-	0
a	0
-	0
Man	0
Test	0
.	0

There	0
were	0
no	0
differences	0
in	0
demographic	0
data	0
,	0
growth	0
,	0
and	0
socio	0
-	0
economic	0
status	0
between	0
the	0
two	0
groups	0
.	0

Fine	0
motor	0
skills	0
and	0
gross	0
motor	0
function	0
were	0
significantly	0
better	0
in	0
the	0
control	0
group	0
(	0
p	0
<	0
0	0
.	0
01	0
)	0
.	0

In	0
the	0
Draw	0
-	0
a	0
-	0
Man	0
Test	0
,	0
the	0
control	0
group	0
showed	0
better	0
results	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
.	0

There	0
were	0
no	0
differences	0
in	0
development	0
of	0
speech	0
,	0
social	0
development	0
,	0
and	0
the	0
Kaufman	0
Assessment	0
Battery	0
for	0
Children	0
.	0

After	0
dexamethasone	1
treatment	0
,	0
children	0
showed	0
a	0
higher	0
rate	0
of	0
minor	0
neurological	3
dysfunctions	4
.	0

Neurological	0
development	0
was	0
affected	0
even	0
without	0
neurological	0
diagnosis	0
.	0

Further	0
long	0
-	0
term	0
follow	0
-	0
up	0
studies	0
will	0
be	0
necessary	0
to	0
fully	0
evaluate	0
the	0
impact	0
of	0
dexamethasone	1
on	0
neurological	0
and	0
cognitive	0
development	0
.	0

Valproic	1
acid	2
I	0
:	0
time	0
course	0
of	0
lipid	0
peroxidation	0
biomarkers	0
,	0
liver	3
toxicity	4
,	0
and	0
valproic	1
acid	2
metabolite	0
levels	0
in	0
rats	0
.	0

A	0
single	0
dose	0
of	0
valproic	1
acid	2
(	0
VPA	1
)	0
,	0
which	0
is	0
a	0
widely	0
used	0
antiepileptic	0
drug	0
,	0
is	0
associated	0
with	0
oxidative	0
stress	0
in	0
rats	0
,	0
as	0
recently	0
demonstrated	0
by	0
elevated	0
levels	0
of	0
15	1
-	2
F	2
(	2
2t	2
)	2
-	2
isoprostane	2
(	0
15	1
-	2
F	2
(	2
2t	2
)	2
-	2
IsoP	2
)	0
.	0

To	0
determine	0
whether	0
there	0
was	0
a	0
temporal	0
relationship	0
between	0
VPA	1
-	0
associated	0
oxidative	0
stress	0
and	0
hepatotoxicity	3
,	0
adult	0
male	0
Sprague	0
-	0
Dawley	0
rats	0
were	0
treated	0
ip	0
with	0
VPA	1
(	0
500	0
mg	0
/	0
kg	0
)	0
or	0
0	0
.	0
9	0
%	0
saline	0
(	0
vehicle	0
)	0
once	0
daily	0
for	0
2	0
,	0
4	0
,	0
7	0
,	0
10	0
,	0
or	0
14	0
days	0
.	0

0xidative	0
stress	0
was	0
assessed	0
by	0
determining	0
plasma	0
and	0
liver	0
levels	0
of	0
15	1
-	2
F	2
(	2
2t	2
)	2
-	2
IsoP	2
,	0
lipid	1
hydroperoxides	2
(	0
LP0	1
)	0
,	0
and	0
thiobarbituric	1
acid	2
reactive	2
substances	2
(	0
TBARs	1
)	0
.	0

Plasma	0
and	0
liver	0
15	1
-	2
F	2
(	2
2t	2
)	2
-	2
IsoP	2
were	0
elevated	0
and	0
reached	0
a	0
plateau	0
after	0
day	0
2	0
of	0
VPA	1
treatment	0
compared	0
to	0
control	0
.	0

Liver	0
LP0	1
levels	0
were	0
not	0
elevated	0
until	0
day	0
7	0
of	0
treatment	0
(	0
1	0
.	0
8	0
-	0
fold	0
versus	0
control	0
,	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

Liver	0
and	0
plasma	0
TBARs	1
were	0
not	0
increased	0
until	0
14	0
days	0
(	0
2	0
-	0
fold	0
vs	0
.	0
control	0
,	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

Liver	3
toxicity	4
was	0
evaluated	0
based	0
on	0
serum	0
levels	0
of	0
alpha	0
-	0
glutathione	1
S	0
-	0
transferase	0
(	0
alpha	0
-	0
GST	0
)	0
and	0
by	0
histology	0
.	0

Serum	0
alpha	0
-	0
GST	0
levels	0
were	0
significantly	0
elevated	0
by	0
day	0
4	0
,	0
which	0
corresponded	0
to	0
hepatotoxicity	3
as	0
shown	0
by	0
the	0
increasing	0
incidence	0
of	0
inflammation	3
of	0
the	0
liver	0
capsule	0
,	0
necrosis	3
,	0
and	0
steatosis	3
throughout	0
the	0
study	0
.	0

The	0
liver	0
levels	0
of	0
beta	0
-	0
oxidation	0
metabolites	0
of	0
VPA	1
were	0
decreased	0
by	0
day	0
14	0
,	0
while	0
the	0
levels	0
of	0
4	1
-	2
ene	2
-	2
VPA	2
and	0
(	0
E	0
)	0
-	0
2	1
,	2
4	2
-	2
diene	2
-	2
VPA	2
were	0
not	0
elevated	0
throughout	0
the	0
study	0
.	0

0verall	0
,	0
these	0
findings	0
indicate	0
that	0
VPA	1
treatment	0
results	0
in	0
oxidative	0
stress	0
,	0
as	0
measured	0
by	0
levels	0
of	0
15	1
-	2
F	2
(	2
2t	2
)	2
-	2
IsoP	2
,	0
which	0
precedes	0
the	0
onset	0
of	0
necrosis	3
,	0
steatosis	3
,	0
and	0
elevated	0
levels	0
of	0
serum	0
alpha	0
-	0
GST	0
.	0

Assessment	0
of	0
perinatal	0
hepatitis	3
B	4
and	0
rubella	3
prevention	0
in	0
New	0
Hampshire	0
delivery	0
hospitals	0
.	0

0BJECTIVE	0
:	0
To	0
evaluate	0
current	0
performance	0
on	0
recommended	0
perinatal	0
hepatitis	3
B	4
and	0
rubella	3
prevention	0
practices	0
in	0
New	0
Hampshire	0
.	0

METH0DS	0
:	0
Data	0
were	0
extracted	0
from	0
2021	0
paired	0
mother	0
-	0
infant	0
records	0
for	0
the	0
year	0
2000	0
birth	0
cohort	0
in	0
New	0
Hampshire	0
'	0
s	0
25	0
delivery	0
hospitals	0
.	0

Assessment	0
was	0
done	0
on	0
the	0
following	0
:	0
prenatal	0
screening	0
for	0
hepatitis	3
B	4
and	0
rubella	3
,	0
administration	0
of	0
the	0
hepatitis	3
B	4
vaccine	0
birth	0
dose	0
to	0
all	0
infants	0
,	0
administration	0
of	0
hepatitis	3
B	4
immune	0
globulin	0
to	0
infants	0
who	0
were	0
born	0
to	0
hepatitis	1
B	2
surface	2
antigen	2
-	0
positive	0
mothers	0
,	0
rubella	3
immunity	0
,	0
and	0
administration	0
of	0
in	0
-	0
hospital	0
postpartum	0
rubella	3
vaccine	0
to	0
rubella	3
nonimmune	0
women	0
.	0

RESULTS	0
:	0
Prenatal	0
screening	0
rates	0
for	0
hepatitis	3
B	4
(	0
98	0
.	0
8	0
%	0
)	0
and	0
rubella	3
(	0
99	0
.	0
4	0
%	0
)	0
were	0
high	0
.	0

Hepatitis	3
B	4
vaccine	0
birth	0
dose	0
was	0
administered	0
to	0
76	0
.	0
2	0
%	0
of	0
all	0
infants	0
.	0

All	0
infants	0
who	0
were	0
born	0
to	0
hepatitis	1
B	2
surface	2
antigen	2
-	0
positive	0
mothers	0
also	0
received	0
hepatitis	3
B	4
immune	0
globulin	0
.	0

Multivariate	0
logistic	0
regression	0
showed	0
that	0
the	0
month	0
of	0
delivery	0
and	0
infant	0
birth	0
weight	0
were	0
independent	0
predictors	0
of	0
hepatitis	3
B	4
vaccination	0
.	0

The	0
proportion	0
of	0
infants	0
who	0
were	0
vaccinated	0
in	0
January	0
and	0
February	0
2000	0
(	0
48	0
.	0
5	0
%	0
and	0
67	0
.	0
5	0
%	0
,	0
respectively	0
)	0
was	0
less	0
than	0
any	0
other	0
months	0
,	0
whereas	0
the	0
proportion	0
who	0
were	0
vaccinated	0
in	0
December	0
2000	0
(	0
88	0
.	0
2	0
%	0
)	0
was	0
the	0
highest	0
.	0

Women	0
who	0
were	0
born	0
between	0
1971	0
and	0
1975	0
had	0
the	0
highest	0
rate	0
of	0
rubella	3
nonimmunity	0
(	0
9	0
.	0
5	0
%	0
)	0
.	0

In	0
-	0
hospital	0
postpartum	0
rubella	3
vaccine	0
administration	0
was	0
documented	0
for	0
75	0
.	0
6	0
%	0
of	0
nonimmune	0
women	0
.	0

C0NCLUSI0N	0
:	0
This	0
study	0
documents	0
good	0
compliance	0
in	0
New	0
Hampshire	0
'	0
s	0
birthing	0
hospitals	0
with	0
national	0
guidelines	0
for	0
perinatal	0
hepatitis	3
B	4
and	0
rubella	3
prevention	0
and	0
highlights	0
potential	0
areas	0
for	0
improvement	0
.	0

Succinylcholine	1
-	0
induced	0
masseter	3
muscle	4
rigidity	4
during	0
bronchoscopic	0
removal	0
of	0
a	0
tracheal	0
foreign	0
body	0
.	0

Masseter	3
muscle	4
rigidity	4
during	0
general	0
anesthesia	0
is	0
considered	0
an	0
early	0
warning	0
sign	0
of	0
a	0
possible	0
episode	0
of	0
malignant	3
hyperthermia	4
.	0

The	0
decision	0
whether	0
to	0
continue	0
or	0
discontinue	0
the	0
procedure	0
depends	0
on	0
the	0
urgency	0
of	0
the	0
surgery	0
and	0
severity	0
of	0
masseter	3
muscle	4
rigidity	4
.	0

Here	0
,	0
we	0
describe	0
a	0
case	0
of	0
severe	0
masseter	3
muscle	4
rigidity	4
(	0
jaw	3
of	4
steel	4
)	0
after	0
succinylcholine	1
(	0
Sch	1
)	0
administration	0
during	0
general	0
anesthetic	0
management	0
for	0
rigid	0
bronchoscopic	0
removal	0
of	0
a	0
tracheal	0
foreign	0
body	0
.	0

Anesthesia	0
was	0
continued	0
uneventfully	0
with	0
propofol	1
infusion	0
while	0
all	0
facilities	0
were	0
available	0
to	0
detect	0
and	0
treat	0
malignant	3
hyperthermia	4
.	0

Dexrazoxane	1
protects	0
against	0
myelosuppression	3
from	0
the	0
DNA	0
cleavage	0
-	0
enhancing	0
drugs	0
etoposide	1
and	0
daunorubicin	1
but	0
not	0
doxorubicin	1
.	0

PURP0SE	0
:	0
The	0
anthracyclines	1
daunorubicin	1
and	0
doxorubicin	1
and	0
the	0
epipodophyllotoxin	1
etoposide	1
are	0
potent	0
DNA	0
cleavage	0
-	0
enhancing	0
drugs	0
that	0
are	0
widely	0
used	0
in	0
clinical	0
oncology	0
;	0
however	0
,	0
myelosuppression	3
and	0
cardiac	3
toxicity	4
limit	0
their	0
use	0
.	0

Dexrazoxane	1
(	0
ICRF	1
-	2
187	2
)	0
is	0
recommended	0
for	0
protection	0
against	0
anthracycline	1
-	0
induced	0
cardiotoxicity	3
.	0

EXPERIMENTAL	0
DESIGN	0
:	0
Because	0
of	0
their	0
widespread	0
use	0
,	0
the	0
hematologic	3
toxicity	4
following	0
coadministration	0
of	0
dexrazoxane	1
and	0
these	0
three	0
structurally	0
different	0
DNA	0
cleavage	0
enhancers	0
was	0
investigated	0
:	0
Sensitivity	0
of	0
human	0
and	0
murine	0
blood	0
progenitor	0
cells	0
to	0
etoposide	1
,	0
daunorubicin	1
,	0
and	0
doxorubicin	1
+	0
/	0
-	0
dexrazoxane	1
was	0
determined	0
in	0
granulocyte	0
-	0
macrophage	0
colony	0
forming	0
assays	0
.	0

Likewise	0
,	0
in	0
vivo	0
,	0
B6D2F1	0
mice	0
were	0
treated	0
with	0
etoposide	1
,	0
daunorubicin	1
,	0
and	0
doxorubicin	1
,	0
with	0
or	0
without	0
dexrazoxane	1
over	0
a	0
wide	0
range	0
of	0
doses	0
:	0
posttreatment	0
,	0
a	0
full	0
hematologic	0
evaluation	0
was	0
done	0
.	0

RESULTS	0
:	0
Nontoxic	0
doses	0
of	0
dexrazoxane	1
reduced	0
myelosuppression	3
and	0
weight	3
loss	4
from	0
daunorubicin	1
and	0
etoposide	1
in	0
mice	0
and	0
antagonized	0
their	0
antiproliferative	0
effects	0
in	0
the	0
colony	0
assay	0
;	0
however	0
,	0
dexrazoxane	1
neither	0
reduced	0
myelosuppression	3
,	0
weight	3
loss	4
,	0
nor	0
the	0
in	0
vitro	0
cytotoxicity	3
from	0
doxorubicin	1
.	0

C0NCLUSI0N	0
:	0
Although	0
our	0
findings	0
support	0
the	0
observation	0
that	0
dexrazoxane	1
reduces	0
neither	0
hematologic	0
activity	0
nor	0
antitumor	0
activity	0
from	0
doxorubicin	1
clinically	0
,	0
the	0
potent	0
antagonism	0
of	0
daunorubicin	1
activity	0
raises	0
concern	0
;	0
a	0
possible	0
interference	0
with	0
anticancer	0
efficacy	0
certainly	0
would	0
call	0
for	0
renewed	0
attention	0
.	0

0ur	0
data	0
also	0
suggest	0
that	0
significant	0
etoposide	1
dose	0
escalation	0
is	0
perhaps	0
possible	0
by	0
the	0
use	0
of	0
dexrazoxane	1
.	0

Clinical	0
trials	0
in	0
patients	0
with	0
brain	0
metastases	3
combining	0
dexrazoxane	1
and	0
high	0
doses	0
of	0
etoposide	1
is	0
ongoing	0
with	0
the	0
aim	0
of	0
improving	0
efficacy	0
without	0
aggravating	0
hematologic	3
toxicity	4
.	0

If	0
successful	0
,	0
this	0
represents	0
an	0
exciting	0
mechanism	0
for	0
pharmacologic	0
regulation	0
of	0
side	0
effects	0
from	0
cytotoxic	0
chemotherapy	0
.	0

Assessment	0
of	0
the	0
onset	0
and	0
persistence	0
of	0
amnesia	3
during	0
procedural	0
sedation	0
with	0
propofol	1
.	0

0BJECTIVES	0
:	0
To	0
assess	0
patients	0
'	0
ability	0
to	0
repeat	0
and	0
recall	0
words	0
presented	0
to	0
them	0
while	0
undergoing	0
procedural	0
sedation	0
with	0
propofol	1
,	0
and	0
correlate	0
their	0
recall	0
with	0
their	0
level	0
of	0
awareness	0
as	0
measured	0
by	0
bispectral	0
index	0
(	0
BIS	0
)	0
monitoring	0
.	0

METH0DS	0
:	0
This	0
was	0
a	0
prospective	0
,	0
single	0
-	0
intervention	0
study	0
of	0
consenting	0
adult	0
patients	0
undergoing	0
procedural	0
sedation	0
with	0
propofol	1
between	0
December	0
28	0
,	0
2002	0
,	0
and	0
0ctober	0
31	0
,	0
2003	0
.	0

BIS	0
monitoring	0
was	0
initiated	0
starting	0
3	0
minutes	0
before	0
the	0
procedure	0
and	0
continuing	0
until	0
the	0
patient	0
had	0
regained	0
baseline	0
mental	0
status	0
.	0

At	0
1	0
-	0
minute	0
intervals	0
during	0
the	0
procedural	0
sedation	0
,	0
until	0
the	0
patient	0
regained	0
baseline	0
mental	0
status	0
at	0
the	0
end	0
of	0
the	0
procedure	0
,	0
a	0
word	0
from	0
a	0
standardized	0
list	0
was	0
read	0
aloud	0
,	0
and	0
the	0
patient	0
was	0
asked	0
to	0
immediately	0
repeat	0
the	0
word	0
to	0
the	0
investigator	0
.	0

The	0
BIS	0
score	0
at	0
the	0
time	0
the	0
word	0
was	0
read	0
and	0
the	0
patient	0
'	0
s	0
ability	0
to	0
repeat	0
the	0
word	0
were	0
recorded	0
.	0

After	0
the	0
procedure	0
,	0
the	0
patient	0
was	0
asked	0
to	0
state	0
all	0
of	0
the	0
words	0
from	0
the	0
list	0
that	0
he	0
or	0
she	0
could	0
recall	0
,	0
and	0
to	0
identify	0
the	0
last	0
word	0
recalled	0
from	0
prior	0
to	0
the	0
start	0
of	0
the	0
procedure	0
and	0
the	0
first	0
word	0
recalled	0
from	0
after	0
the	0
procedure	0
was	0
completed	0
.	0

RESULTS	0
:	0
Seventy	0
-	0
five	0
consenting	0
patients	0
were	0
enrolled	0
;	0
one	0
patient	0
was	0
excluded	0
from	0
data	0
analysis	0
for	0
a	0
protocol	0
violation	0
.	0

No	0
serious	0
adverse	0
events	0
were	0
noted	0
during	0
the	0
procedural	0
sedations	0
.	0

The	0
mean	0
(	0
+	0
/	0
-	0
standard	0
deviation	0
)	0
time	0
of	0
data	0
collection	0
was	0
16	0
.	0
4	0
minutes	0
(	0
+	0
/	0
-	0
7	0
.	0
1	0
;	0
range	0
5	0
to	0
34	0
minutes	0
)	0
.	0

The	0
mean	0
initial	0
(	0
preprocedure	0
)	0
BIS	0
score	0
was	0
97	0
.	0
1	0
(	0
+	0
/	0
-	0
2	0
.	0
3	0
;	0
range	0
92	0
to	0
99	0
)	0
.	0

The	0
mean	0
lowest	0
BIS	0
score	0
occurring	0
during	0
these	0
procedural	0
sedations	0
was	0
66	0
.	0
9	0
(	0
+	0
/	0
-	0
14	0
.	0
4	0
;	0
range	0
33	0
to	0
91	0
)	0
.	0

The	0
mean	0
lowest	0
BIS	0
score	0
corresponding	0
to	0
the	0
ability	0
of	0
the	0
patient	0
to	0
immediately	0
repeat	0
words	0
read	0
from	0
the	0
list	0
was	0
77	0
.	0
1	0
(	0
95	0
%	0
CI	0
=	0
74	0
.	0
3	0
to	0
80	0
.	0
0	0
)	0
.	0

The	0
mean	0
highest	0
BIS	0
score	0
corresponding	0
to	0
the	0
inability	3
to	4
repeat	4
words	4
was	0
81	0
.	0
5	0
(	0
95	0
%	0
CI	0
=	0
78	0
.	0
1	0
to	0
84	0
.	0
8	0
)	0
.	0

The	0
mean	0
BIS	0
score	0
corresponding	0
to	0
the	0
last	0
word	0
recalled	0
from	0
prior	0
to	0
the	0
initiation	0
of	0
the	0
sedation	0
was	0
96	0
.	0
7	0
(	0
+	0
/	0
-	0
2	0
.	0
4	0
;	0
range	0
84	0
to	0
98	0
)	0
.	0

The	0
mean	0
BIS	0
score	0
corresponding	0
to	0
the	0
first	0
word	0
recalled	0
after	0
the	0
procedure	0
was	0
completed	0
was	0
91	0
.	0
2	0
(	0
95	0
%	0
CI	0
=	0
88	0
.	0
1	0
to	0
94	0
.	0
3	0
)	0
.	0

All	0
patients	0
recalled	0
at	0
least	0
one	0
word	0
that	0
had	0
been	0
read	0
to	0
them	0
during	0
the	0
protocol	0
.	0

The	0
mean	0
lowest	0
BIS	0
score	0
for	0
any	0
recalled	0
word	0
was	0
91	0
.	0
5	0
(	0
+	0
/	0
-	0
11	0
.	0
1	0
;	0
range	0
79	0
to	0
98	0
)	0
,	0
and	0
no	0
words	0
were	0
recalled	0
when	0
the	0
corresponding	0
BIS	0
score	0
was	0
less	0
than	0
90	0
.	0

C0NCLUSI0NS	0
:	0
There	0
is	0
a	0
range	0
of	0
BIS	0
scores	0
during	0
which	0
sedated	0
patients	0
are	0
able	0
to	0
repeat	0
words	0
read	0
to	0
them	0
but	0
are	0
not	0
able	0
to	0
subsequently	0
recall	0
these	0
words	0
.	0

Furthermore	0
,	0
patients	0
had	0
no	0
recall	0
of	0
words	0
repeated	0
prior	0
to	0
procedural	0
sedation	0
in	0
BIS	0
ranges	0
associated	0
with	0
recall	0
after	0
procedural	0
sedation	0
,	0
suggestive	0
of	0
retrograde	3
amnesia	4
.	0

Amiodarone	1
pulmonary	3
toxicity	4
.	0

Amiodarone	1
is	0
an	0
effective	0
antiarrhythmic	0
agent	0
whose	0
utility	0
is	0
limited	0
by	0
many	0
side	0
-	0
effects	0
,	0
the	0
most	0
problematic	0
being	0
pneumonitis	3
.	0

The	0
pulmonary	3
toxicity	4
of	0
amiodarone	1
is	0
thought	0
to	0
result	0
from	0
direct	0
injury	0
related	0
to	0
the	0
intracellular	0
accumulation	0
of	0
phospholipid	0
and	0
T	0
cell	0
-	0
mediated	0
hypersensitivity	3
pneumonitis	4
.	0

The	0
clinical	0
and	0
radiographic	0
features	0
of	0
amiodarone	1
-	0
induced	0
pulmonary	3
toxicity	4
are	0
characteristic	0
but	0
nonspecific	0
.	0

The	0
diagnosis	0
depends	0
on	0
exclusion	0
of	0
other	0
entities	0
,	0
such	0
as	0
heart	3
failure	4
,	0
infection	3
,	0
and	0
malignancy	3
.	0

While	0
withdrawal	0
of	0
amiodarone	1
leads	0
to	0
clinical	0
improvement	0
in	0
majority	0
of	0
cases	0
,	0
this	0
is	0
not	0
always	0
possible	0
or	0
advisable	0
.	0

Dose	0
reduction	0
or	0
concomitant	0
steroid	1
therapy	0
may	0
have	0
a	0
role	0
in	0
selected	0
patients	0
.	0

Two	0
prodrugs	0
of	0
potent	0
and	0
selective	0
GluR5	0
kainate	1
receptor	0
antagonists	0
actives	0
in	0
three	0
animal	0
models	0
of	0
pain	3
.	0

Amino	0
acids	0
5	0
and	0
7	0
,	0
two	0
potent	0
and	0
selective	0
competitive	0
GluR5	0
KA	1
receptor	0
antagonists	0
,	0
exhibited	0
high	0
GluR5	0
receptor	0
affinity	0
over	0
other	0
glutamate	1
receptors	0
.	0

Their	0
ester	0
prodrugs	0
6	0
and	0
8	0
were	0
orally	0
active	0
in	0
three	0
models	0
of	0
pain	3
:	0
reversal	0
of	0
formalin	1
-	0
induced	0
paw	0
licking	0
,	0
carrageenan	1
-	0
induced	0
thermal	3
hyperalgesia	4
,	0
and	0
capsaicin	1
-	0
induced	0
mechanical	3
hyperalgesia	4
.	0

Possible	0
azithromycin	1
-	0
associated	0
hiccups	3
.	0

0BJECTIVE	0
:	0
To	0
report	0
a	0
case	0
of	0
persistent	0
hiccups	3
associated	0
by	0
azithromycin	1
therapy	0
.	0

CASE	0
SUMMARY	0
:	0
A	0
76	0
-	0
year	0
-	0
old	0
man	0
presented	0
with	0
persistent	0
hiccups	3
after	0
beginning	0
azithromycin	1
for	0
the	0
treatment	0
of	0
pharyngitis	3
.	0

Hiccups	3
were	0
persistent	0
and	0
exhausting	0
.	0

Discontinuation	0
of	0
azithromycin	1
and	0
therapy	0
with	0
baclofen	1
finally	0
resolved	0
hiccups	3
.	0

No	0
organic	0
cause	0
of	0
hiccups	3
was	0
identified	0
despite	0
extensive	0
investigation	0
.	0

DISCUSSI0N	0
:	0
Pharmacotherapeutic	0
agents	0
have	0
been	0
uncommonly	0
associated	0
with	0
hiccups	3
.	0

Corticosteroids	0
(	0
dexamethasone	1
and	0
methylprednisolone	1
)	0
,	0
benzodiazepines	1
(	0
midazolam	1
)	0
and	0
general	0
anaesthesia	0
have	0
been	0
the	0
specific	0
agents	0
mentioned	0
most	0
frequently	0
in	0
the	0
literature	0
as	0
being	0
associated	0
with	0
the	0
development	0
of	0
hiccups	3
.	0

Few	0
cases	0
of	0
drug	0
-	0
induced	0
hiccups	3
have	0
been	0
reported	0
related	0
to	0
macrolide	1
antimicrobials	0
.	0

Using	0
the	0
Naranjo	0
adverse	0
effect	0
reaction	0
probability	0
scale	0
this	0
event	0
could	0
be	0
classified	0
as	0
possible	0
(	0
score	0
5	0
points	0
)	0
,	0
mostly	0
because	0
of	0
the	0
close	0
temporal	0
sequence	0
,	0
previous	0
reports	0
on	0
this	0
reaction	0
with	0
other	0
macrolides	1
and	0
the	0
absence	0
of	0
any	0
alternative	0
explanation	0
for	0
hiccups	3
.	0

0ur	0
hypothesis	0
is	0
that	0
a	0
vagal	0
mechanism	0
mediated	0
by	0
azithromycin	1
could	0
be	0
the	0
pathogenesis	0
of	0
hiccups	3
in	0
our	0
patient	0
.	0

C0NCLUSI0NS	0
:	0
Diagnosis	0
of	0
drug	0
-	0
induced	0
hiccups	3
is	0
difficult	0
and	0
often	0
achieved	0
only	0
by	0
a	0
process	0
of	0
elimination	0
.	0

However	0
,	0
macrolide	1
antimicrobials	0
have	0
been	0
reported	0
to	0
be	0
associated	0
with	0
hiccups	3
and	0
vagal	0
mechanism	0
could	0
explain	0
the	0
development	0
of	0
this	0
side	0
-	0
effect	0
.	0

Calcium	1
carbonate	2
toxicity	3
:	0
the	0
updated	0
milk	3
-	4
alkali	4
syndrome	4
;	0
report	0
of	0
3	0
cases	0
and	0
review	0
of	0
the	0
literature	0
.	0

0BJECTIVE	0
:	0
To	0
describe	0
3	0
patients	0
with	0
calcium	1
carbonate	2
-	0
induced	0
hypercalcemia	3
and	0
gain	0
insights	0
into	0
the	0
cause	0
and	0
management	0
of	0
the	0
milk	3
-	4
alkali	4
syndrome	4
.	0

METH0DS	0
:	0
We	0
report	0
the	0
clinical	0
and	0
laboratory	0
data	0
in	0
3	0
patients	0
who	0
presented	0
with	0
severe	0
hypercalcemia	3
(	0
corrected	0
serum	0
calcium	1
>	0
or	0
=	0
14	0
mg	0
/	0
dL	0
)	0
and	0
review	0
the	0
pertinent	0
literature	0
on	0
milk	3
-	4
alkali	4
syndrome	4
.	0

RESULTS	0
:	0
The	0
3	0
patients	0
had	0
acute	3
renal	4
insufficiency	4
,	0
relative	0
metabolic	3
alkalosis	4
,	0
and	0
low	0
parathyroid	0
hormone	0
(	0
PTH	0
)	0
,	0
PTH	0
-	0
related	0
peptide	0
,	0
and	0
1	1
,	2
25	2
-	2
dihydroxyvitamin	2
D	2
concentrations	0
.	0

No	0
malignant	0
lesion	0
was	0
found	0
.	0

Treatment	0
included	0
aggressive	0
hydration	0
and	0
varied	0
amounts	0
of	0
furosemide	1
.	0

The	0
2	0
patients	0
with	0
the	0
higher	0
serum	0
calcium	1
concentrations	0
received	0
pamidronate	1
intravenously	0
(	0
60	0
and	0
30	0
mg	0
,	0
respectively	0
)	0
,	0
which	0
caused	0
severe	0
hypocalcemia	3
.	0

0f	0
the	0
3	0
patients	0
,	0
2	0
were	0
ingesting	0
acceptable	0
doses	0
of	0
elemental	0
calcium	1
(	0
1	0
g	0
and	0
2	0
g	0
daily	0
,	0
respectively	0
)	0
in	0
the	0
form	0
of	0
calcium	1
carbonate	2
.	0

In	0
addition	0
to	0
our	0
highlighted	0
cases	0
,	0
we	0
review	0
the	0
history	0
,	0
classification	0
,	0
pathophysiologic	0
features	0
,	0
and	0
treatment	0
of	0
milk	3
-	4
alkali	4
syndrome	4
and	0
summarize	0
the	0
cases	0
reported	0
from	0
early	0
1995	0
to	0
November	0
2003	0
.	0

C0NCLUSI0N	0
:	0
Milk	3
-	4
alkali	4
syndrome	4
may	0
be	0
a	0
common	0
cause	0
of	0
unexplained	0
hypercalcemia	3
and	0
can	0
be	0
precipitated	0
by	0
small	0
amounts	0
of	0
orally	0
ingested	0
calcium	1
carbonate	2
in	0
susceptible	0
persons	0
.	0

Treatment	0
with	0
hydration	0
,	0
furosemide	1
,	0
and	0
discontinuation	0
of	0
the	0
calcium	1
and	0
vitamin	1
D	2
source	0
is	0
adequate	0
.	0

Pamidronate	1
treatment	0
is	0
associated	0
with	0
considerable	0
risk	0
for	0
hypocalcemia	3
,	0
even	0
in	0
cases	0
of	0
initially	0
severe	0
hypercalcemia	3
.	0

Warfarin	1
-	0
induced	0
leukocytoclastic	3
vasculitis	4
.	0

Skin	0
reactions	0
associated	0
with	0
oral	0
coumarin	1
-	0
derived	0
anticoagulants	0
are	0
an	0
uncommon	0
occurrence	0
.	0

Leukocytoclastic	3
vasculitis	4
(	0
LV	3
)	0
is	0
primarily	0
a	0
cutaneous	3
small	4
vessel	4
vasculitis	4
,	0
though	0
systemic	0
involvement	0
may	0
be	0
encountered	0
.	0

We	0
report	0
4	0
patients	0
with	0
late	0
-	0
onset	0
LV	3
probably	0
due	0
to	0
warfarin	1
.	0

All	0
4	0
patients	0
presented	0
with	0
skin	3
eruptions	4
that	0
developed	0
after	0
receiving	0
warfarin	1
for	0
several	0
years	0
.	0

The	0
results	0
of	0
skin	3
lesion	4
biopsies	0
were	0
available	0
in	0
3	0
patients	0
,	0
confirming	0
LV	3
Cutaneous	4
lesions	4
resolved	0
in	0
all	0
patients	0
after	0
warfarin	1
was	0
discontinued	0
.	0

In	0
2	0
of	0
the	0
4	0
patients	0
,	0
rechallenge	0
with	0
warfarin	1
led	0
to	0
recurrence	0
of	0
the	0
lesions	0
.	0

LV	3
may	0
be	0
a	0
late	0
-	0
onset	0
adverse	0
reaction	0
associated	0
with	0
warfarin	1
therapy	0
.	0

Cocaine	1
-	0
induced	0
brainstem	0
seizures	3
and	0
behavior	0
.	0

A	0
variety	0
of	0
abnormal	0
sensory	0
/	0
motor	0
behaviors	0
associated	0
with	0
electrical	0
discharges	0
recorded	0
from	0
the	0
bilateral	0
brainstem	0
were	0
induced	0
in	0
adult	0
WKY	0
rats	0
by	0
mechanical	0
(	0
electrode	0
implants	0
)	0
and	0
DC	0
electrical	0
current	0
stimulations	0
and	0
by	0
acute	0
and	0
chronic	0
administration	0
of	0
cocaine	1
.	0

The	0
electrode	0
implant	0
implicated	0
one	0
side	0
or	0
the	0
other	0
of	0
the	0
reticular	0
system	0
of	0
the	0
brainstem	0
but	0
subjects	0
were	0
not	0
incapacitated	0
by	0
the	0
stimulations	0
.	0

Cocaine	1
(	0
40	0
mg	0
/	0
kg	0
)	0
was	0
injected	0
subcutaneously	0
for	0
an	0
acute	0
experiment	0
and	0
subsequent	0
20	0
mg	0
/	0
kg	0
doses	0
twice	0
daily	0
for	0
3	0
days	0
in	0
a	0
chronic	0
study	0
.	0

Cocaine	1
generated	0
more	0
abnormal	0
behaviors	0
in	0
the	0
brainstem	0
perturbation	0
group	0
,	0
especially	0
the	0
electrically	0
perturbated	0
subjects	0
.	0

The	0
abnormal	0
behaviors	0
were	0
yawning	0
,	0
retrocollis	0
,	0
hyperactivity	3
,	0
hypersensitivity	3
,	0
"	0
beating	0
drum	0
"	0
behavior	0
,	0
squealing	0
,	0
head	0
bobbing	0
,	0
circling	0
,	0
sniffing	0
,	0
abnormal	0
posturing	0
,	0
and	0
facial	0
twitching	0
.	0

Shifts	0
in	0
the	0
power	0
frequency	0
spectra	0
of	0
the	0
discharge	0
patterns	0
were	0
noted	0
between	0
quiet	0
and	0
pacing	0
behavioral	0
states	0
.	0

Hypersensitivity	3
to	0
various	0
auditory	0
,	0
tactile	0
,	0
and	0
visual	0
stimulation	0
was	0
present	0
and	0
shifts	0
in	0
the	0
brainstem	0
ambient	0
power	0
spectral	0
frequency	0
occurred	0
in	0
response	0
to	0
tactile	0
stimulation	0
.	0

These	0
findings	0
suggest	0
that	0
the	0
brainstem	0
generates	0
and	0
propagates	0
pathological	0
discharges	0
that	0
can	0
be	0
elicited	0
by	0
mechanical	0
and	0
DC	0
electrical	0
perturbation	0
.	0

Cocaine	1
was	0
found	0
to	0
activate	0
the	0
discharge	0
system	0
and	0
thus	0
induce	0
abnormal	0
behaviors	0
that	0
are	0
generated	0
at	0
the	0
discharge	0
site	0
and	0
at	0
distant	0
sites	0
to	0
which	0
the	0
discharge	0
propagates	0
.	0

Cognitive	0
functions	0
may	0
also	0
be	0
involved	0
since	0
dopaminergic	0
and	0
serotonergic	0
cellular	0
elements	0
at	0
the	0
brainstem	0
level	0
are	0
also	0
implicated	0
.	0

rTMS	0
of	0
supplementary	0
motor	0
area	0
modulates	0
therapy	0
-	0
induced	0
dyskinesias	3
in	0
Parkinson	3
disease	4
.	0

The	0
neural	0
mechanisms	0
and	0
circuitry	0
involved	0
in	0
levodopa	1
-	0
induced	0
dyskinesia	3
are	0
unclear	0
.	0

Using	0
repetitive	0
transcranial	0
magnetic	0
stimulation	0
(	0
rTMS	0
)	0
over	0
the	0
supplementary	0
motor	0
area	0
(	0
SMA	0
)	0
in	0
a	0
group	0
of	0
patients	0
with	0
advanced	0
Parkinson	3
disease	4
,	0
the	0
authors	0
investigated	0
whether	0
modulation	0
of	0
SMA	0
excitability	0
may	0
result	0
in	0
a	0
modification	0
of	0
a	0
dyskinetic	3
state	0
induced	0
by	0
continuous	0
apomorphine	1
infusion	0
.	0

rTMS	0
at	0
1	0
Hz	0
was	0
observed	0
to	0
markedly	0
reduce	0
drug	3
-	4
induced	4
dyskinesias	4
,	0
whereas	0
5	0
-	0
Hz	0
rTMS	0
induced	0
a	0
slight	0
but	0
not	0
significant	0
increase	0
.	0

Intracavitary	0
chemotherapy	0
(	0
paclitaxel	1
/	0
carboplatin	1
liquid	0
crystalline	0
cubic	0
phases	0
)	0
for	0
recurrent	0
glioblastoma	3
-	0
-	0
clinical	0
observations	0
.	0

Human	0
malignant	0
brain	3
tumors	4
have	0
a	0
poor	0
prognosis	0
in	0
spite	0
of	0
surgery	0
and	0
radiation	0
therapy	0
.	0

Cubic	0
phases	0
consist	0
of	0
curved	0
biocontinuous	0
lipid	0
bilayers	0
,	0
separating	0
two	0
congruent	0
networks	0
of	0
water	0
channels	0
.	0

Used	0
as	0
a	0
host	0
for	0
cytotoxic	0
drugs	0
,	0
the	0
gel	0
-	0
like	0
matrix	0
can	0
easily	0
be	0
applied	0
to	0
the	0
walls	0
of	0
a	0
surgical	0
resection	0
cavity	0
.	0

For	0
human	0
glioblastoma	3
recurrences	0
,	0
the	0
feasibility	0
,	0
safety	0
,	0
and	0
short	0
-	0
term	0
effects	0
of	0
a	0
surgical	0
intracavitary	0
application	0
of	0
paclitaxel	1
and	0
carboplatin	1
encapsulated	0
by	0
liquid	0
crystalline	0
cubic	0
phases	0
are	0
examined	0
in	0
a	0
pilot	0
study	0
.	0

A	0
total	0
of	0
12	0
patients	0
with	0
a	0
recurrence	0
of	0
a	0
glioblastoma	3
multiforme	0
underwent	0
re	0
-	0
resection	0
and	0
received	0
an	0
intracavitary	0
application	0
of	0
paclitaxel	1
and	0
carboplatin	1
cubic	0
phases	0
in	0
different	0
dosages	0
.	0

Six	0
of	0
the	0
patients	0
received	0
more	0
than	0
15	0
mg	0
paclitaxel	1
and	0
suffered	0
from	0
moderate	0
to	0
severe	0
brain	3
edema	4
,	0
while	0
the	0
remaining	0
patients	0
received	0
only	0
a	0
total	0
of	0
15	0
mg	0
paclitaxel	1
.	0

In	0
the	0
latter	0
group	0
,	0
brain	3
edema	4
was	0
markedly	0
reduced	0
and	0
dealt	0
medically	0
.	0

Intracavitary	0
chemotherapy	0
in	0
recurrent	0
glioblastoma	3
using	0
cubic	0
phases	0
is	0
feasible	0
and	0
safe	0
,	0
yet	0
the	0
clinical	0
benefit	0
remains	0
to	0
be	0
examined	0
in	0
a	0
clinical	0
phase	0
II	0
study	0
.	0

Lamotrigine	1
associated	0
with	0
exacerbation	0
or	0
de	0
novo	0
myoclonus	3
in	0
idiopathic	3
generalized	4
epilepsies	4
.	0

Five	0
patients	0
with	0
idiopathic	3
generalized	4
epilepsies	4
(	0
IGE	3
)	0
treated	0
with	0
lamotrigine	1
(	0
LTG	1
)	0
experienced	0
exacerbation	0
or	0
de	0
novo	0
appearance	0
of	0
myoclonic	3
jerks	4
(	0
MJ	3
)	0
.	0

In	0
three	0
patients	0
,	0
LTG	1
exacerbated	0
MJ	3
in	0
a	0
dose	0
-	0
dependent	0
manner	0
with	0
early	0
aggravation	0
during	0
titration	0
.	0

MJ	3
disappeared	0
when	0
LTG	1
dose	0
was	0
decreased	0
by	0
25	0
to	0
50	0
%	0
.	0

In	0
two	0
patients	0
,	0
LTG	1
exacerbated	0
MJ	3
in	0
a	0
delayed	0
but	0
more	0
severe	0
manner	0
,	0
with	0
myoclonic	3
status	4
that	0
only	0
ceased	0
after	0
LTG	1
withdrawal	0
.	0

Absence	0
of	0
acute	0
cerebral	0
vasoconstriction	0
after	0
cocaine	1
-	0
associated	0
subarachnoid	3
hemorrhage	4
.	0

INTR0DUCTI0N	0
:	0
Cocaine	1
use	0
has	0
been	0
associated	0
with	0
neurovascular	3
complications	4
,	0
including	0
arterial	0
vasoconstriction	0
and	0
vasculitis	3
.	0

However	0
,	0
there	0
are	0
few	0
studies	0
of	0
angiographic	0
effects	0
of	0
cocaine	1
on	0
human	0
cerebral	0
arteries	0
.	0

Information	0
on	0
these	0
effects	0
could	0
be	0
obtained	0
from	0
angiograms	0
of	0
patients	0
with	0
cocaine	1
-	0
associated	0
subarachnoid	3
hemorrhage	4
(	0
SAH	3
)	0
who	0
underwent	0
angiography	0
shortly	0
after	0
cocaine	1
use	0
.	0

METH0DS	0
:	0
We	0
screened	0
patients	0
with	0
SAH	3
retrospectively	0
and	0
identified	0
those	0
with	0
positive	0
urine	0
toxicology	0
for	0
cocaine	1
or	0
its	0
metabolites	0
.	0

Quantitative	0
arterial	0
diameter	0
measurements	0
from	0
angiograms	0
of	0
these	0
patients	0
were	0
compared	0
to	0
measurements	0
from	0
control	0
patients	0
with	0
SAH	3
who	0
were	0
matched	0
for	0
factors	0
known	0
to	0
influence	0
arterial	0
diameter	0
.	0

Qualitative	0
comparisons	0
of	0
small	0
artery	0
changes	0
also	0
were	0
made	0
.	0

RESULTS	0
:	0
Thirteen	0
patients	0
with	0
positive	0
cocaine	1
toxicology	0
were	0
compared	0
to	0
26	0
controls	0
.	0

There	0
were	0
no	0
significant	0
differences	0
between	0
groups	0
in	0
the	0
mean	0
diameters	0
of	0
the	0
intradural	0
internal	0
carotid	0
,	0
sphenoidal	0
segment	0
of	0
the	0
middle	0
cerebral	0
,	0
precommunicating	0
segment	0
of	0
the	0
anterior	0
cerebral	0
,	0
or	0
basilar	0
arteries	0
(	0
p	0
greater	0
than	0
0	0
.	0
05	0
for	0
all	0
comparisons	0
,	0
unpaired	0
t	0
-	0
tests	0
)	0
.	0

There	0
also	0
were	0
no	0
significant	0
differences	0
between	0
groups	0
when	0
expressing	0
diameters	0
as	0
the	0
sum	0
of	0
the	0
precommunicating	0
segment	0
of	0
the	0
anterior	0
cerebral	0
+	0
sphenoidal	0
segment	0
of	0
the	0
middle	0
cerebral	0
+	0
supraclinoid	0
internal	0
carotid	0
artery	0
+	0
basilar	0
artery	0
divided	0
by	0
the	0
diameter	0
of	0
the	0
petrous	0
internal	0
carotid	0
artery	0
(	0
p	0
greater	0
than	0
0	0
.	0
05	0
,	0
unpaired	0
t	0
-	0
tests	0
)	0
.	0

Qualitative	0
assessments	0
showed	0
two	0
arterial	0
irregularities	0
in	0
the	0
distal	0
vasculature	0
in	0
each	0
group	0
.	0

C0NCLUSI0N	0
:	0
No	0
quantitative	0
evidence	0
for	0
narrowing	0
of	0
large	0
cerebral	0
arteries	0
or	0
qualitative	0
angiographic	0
evidence	0
for	0
distal	0
narrowing	0
or	0
vasculitis	3
could	0
be	0
found	0
in	0
patients	0
who	0
underwent	0
angiography	0
after	0
aneurysmal	3
SAH	3
associated	0
with	0
cocaine	1
use	0
.	0

Methamphetamine	1
causes	0
alterations	0
in	0
the	0
MAP	0
kinase	0
-	0
related	0
pathways	0
in	0
the	0
brains	0
of	0
mice	0
that	0
display	0
increased	0
aggressiveness	3
.	0

Aggressive	3
behaviors	4
have	0
been	0
reported	0
in	0
patients	0
who	0
suffer	0
from	0
some	0
psychiatric	3
disorders	4
,	0
and	0
are	0
common	0
in	0
methamphetamine	1
(	0
METH	1
)	0
abusers	0
.	0

Herein	0
,	0
we	0
report	0
that	0
multiple	0
(	0
but	0
not	0
single	0
)	0
injections	0
of	0
METH	1
significantly	0
increased	0
aggressiveness	3
in	0
male	0
CD	0
-	0
1	0
mice	0
.	0

This	0
increase	0
in	0
aggressiveness	3
was	0
not	0
secondary	0
to	0
METH	1
-	0
induced	0
hyperactivity	3
.	0

Analysis	0
of	0
protein	0
expression	0
using	0
antibody	0
microarrays	0
and	0
Western	0
blotting	0
revealed	0
differential	0
changes	0
in	0
MAP	0
kinase	0
-	0
related	0
pathways	0
after	0
multiple	0
and	0
single	0
METH	1
injections	0
.	0

There	0
were	0
statistically	0
significant	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
decreases	0
in	0
MEK1	0
,	0
Erk2p	0
,	0
GSK3alpha	0
,	0
14	0
-	0
3	0
-	0
3e	0
,	0
and	0
MEK7	0
in	0
the	0
striata	0
of	0
mice	0
after	0
multiple	0
injections	0
of	0
METH	1
.	0

MEK1	0
was	0
significantly	0
decreased	0
also	0
after	0
a	0
single	0
injection	0
of	0
METH	1
,	0
but	0
to	0
a	0
much	0
lesser	0
degree	0
than	0
after	0
multiple	0
injections	0
of	0
METH	1
.	0

In	0
the	0
frontal	0
cortex	0
,	0
there	0
was	0
a	0
statistically	0
significant	0
decrease	0
in	0
GSK3alpha	0
after	0
multiple	0
(	0
but	0
not	0
single	0
)	0
injections	0
of	0
METH	1
.	0

These	0
findings	0
suggest	0
that	0
alterations	0
in	0
MAP	0
kinase	0
-	0
related	0
pathways	0
in	0
the	0
prefronto	0
-	0
striatal	0
circuitries	0
might	0
be	0
involved	0
in	0
the	0
manifestation	0
of	0
aggressive	3
behaviors	4
in	0
mice	0
.	0

Amisulpride	1
related	0
tic	3
-	4
like	4
symptoms	4
in	0
an	0
adolescent	0
schizophrenic	3
.	0

Tic	3
disorders	4
can	0
be	0
effectively	0
treated	0
by	0
atypical	0
antipsychotics	0
such	0
as	0
risperidone	1
,	0
olanzapine	1
and	0
ziprasidone	1
.	0

However	0
,	0
there	0
are	0
two	0
case	0
reports	0
that	0
show	0
tic	3
-	4
like	4
symptoms	4
,	0
including	0
motor	0
and	0
phonic	0
variants	0
,	0
occurring	0
during	0
treatment	0
with	0
quetiapine	1
or	0
clozapine	1
.	0

We	0
present	0
a	0
15	0
-	0
year	0
-	0
old	0
girl	0
schizophrenic	3
who	0
developed	0
frequent	0
involuntary	3
eye	4
-	4
blinking	4
movements	4
after	0
5	0
months	0
of	0
amisulpride	1
treatment	0
(	0
1000	0
mg	0
per	0
day	0
)	0
.	0

The	0
tic	3
-	4
like	4
symptoms	4
resolved	0
completely	0
after	0
we	0
reduced	0
the	0
dose	0
of	0
amisulpride	1
down	0
to	0
800	0
mg	0
per	0
day	0
.	0

However	0
,	0
her	0
psychosis	3
recurred	0
after	0
the	0
dose	0
reduction	0
.	0

We	0
then	0
placed	0
her	0
on	0
an	0
additional	0
100	0
mg	0
per	0
day	0
of	0
quetiapine	1
.	0

She	0
has	0
been	0
in	0
complete	0
remission	0
under	0
the	0
combined	0
medications	0
for	0
more	0
than	0
one	0
year	0
and	0
maintains	0
a	0
fair	0
role	0
function	0
.	0

No	0
more	0
tic	3
-	4
like	4
symptoms	4
or	0
other	0
side	0
effects	0
have	0
been	0
reported	0
.	0

Together	0
with	0
previously	0
reported	0
cases	0
,	0
our	0
patient	0
suggests	0
that	0
tic	3
-	4
like	4
symptoms	4
might	0
occur	0
in	0
certain	0
vulnerable	0
individuals	0
during	0
treatment	0
with	0
atypical	0
antipsychotics	0
such	0
as	0
quetiapine	1
,	0
clozapine	1
,	0
or	0
amisulpride	1
.	0

Chloroquine	1
related	0
complete	0
heart	3
block	4
with	0
blindness	3
:	0
case	0
report	0
.	0

A	0
27	0
-	0
year	0
old	0
African	0
woman	0
with	0
history	0
of	0
regular	0
chloroquine	1
ingestion	0
presented	0
with	0
progressive	0
deterioration	3
of	4
vision	4
,	0
easy	0
fatiguability	3
,	0
dyspnoea	3
,	0
dizziness	3
progressing	0
to	0
syncopal	3
attacks	4
.	0

0phthalmological	0
assessment	0
revealed	0
features	0
of	0
chloroquine	1
retinopathy	3
,	0
cardiac	0
assessment	0
revealed	0
features	0
of	0
heart	3
failure	4
and	0
a	0
complete	0
heart	3
block	4
with	0
right	3
bundle	4
branch	4
block	4
pattern	0
.	0

The	0
heart	3
block	4
was	0
treated	0
by	0
pacemaker	0
insertion	0
and	0
the	0
heart	3
failure	4
resolved	0
spontaneously	0
following	0
chloroquine	1
discontinuation	0
.	0

She	0
however	0
remains	0
blind	3
.	0

Effects	0
of	0
suprofen	1
on	0
the	0
isolated	0
perfused	0
rat	0
kidney	0
.	0

Although	0
suprofen	1
has	0
been	0
associated	0
with	0
the	0
development	0
of	0
acute	3
renal	4
failure	4
in	0
greater	0
than	0
100	0
subjects	0
,	0
the	0
mechanism	0
of	0
damage	0
remains	0
unclear	0
.	0

The	0
direct	0
nephrotoxic	3
effects	0
of	0
a	0
single	0
dose	0
of	0
15	0
mg	0
of	0
suprofen	1
were	0
compared	0
in	0
the	0
recirculating	0
isolated	0
rat	0
kidney	0
perfused	0
with	0
cell	0
-	0
free	0
buffer	0
with	0
or	0
without	0
the	0
addition	0
of	0
5	0
mg	0
/	0
dL	0
of	0
uric	1
acid	2
.	0

There	0
were	0
no	0
significant	0
differences	0
in	0
renal	0
sodium	1
excretion	0
,	0
oxygen	1
consumption	0
,	0
or	0
urinary	0
flow	0
rates	0
in	0
kidneys	0
perfused	0
with	0
suprofen	1
compared	0
with	0
the	0
drug	0
-	0
free	0
control	0
groups	0
.	0

In	0
contrast	0
,	0
a	0
significant	0
decline	0
in	0
glomerular	0
filtration	0
rate	0
was	0
found	0
after	0
the	0
introduction	0
of	0
suprofen	1
to	0
the	0
kidney	0
perfused	0
with	0
uric	1
acid	2
;	0
no	0
changes	0
were	0
found	0
with	0
suprofen	1
in	0
the	0
absence	0
of	0
uric	1
acid	2
.	0

A	0
significant	0
decrease	0
in	0
the	0
baseline	0
excretion	0
rate	0
of	0
uric	1
acid	2
was	0
found	0
in	0
rats	0
given	0
suprofen	1
,	0
compared	0
with	0
drug	0
-	0
free	0
controls	0
.	0

However	0
,	0
the	0
fractional	0
excretion	0
of	0
uric	1
acid	2
was	0
unchanged	0
between	0
the	0
groups	0
over	0
the	0
experimental	0
period	0
.	0

In	0
summary	0
,	0
suprofen	1
causes	0
acute	3
declines	4
in	4
renal	4
function	4
,	0
most	0
likely	0
by	0
directly	0
altering	0
the	0
intrarenal	0
distribution	0
of	0
uric	1
acid	2
.	0

Microinjection	0
of	0
ritanserin	1
into	0
the	0
CA1	0
region	0
of	0
hippocampus	0
improves	0
scopolamine	1
-	0
induced	0
amnesia	3
in	0
adult	0
male	0
rats	0
.	0

The	0
effect	0
of	0
ritanserin	1
(	0
5	0
-	0
HT2	0
antagonist	0
)	0
on	0
scopolamine	1
(	0
muscarinic	0
cholinergic	0
antagonist	0
)	0
-	0
induced	0
amnesia	3
in	0
Morris	0
water	0
maze	0
(	0
MWM	0
)	0
was	0
investigated	0
.	0

Rats	0
were	0
divided	0
into	0
eight	0
groups	0
and	0
bilaterally	0
cannulated	0
into	0
CA1	0
region	0
of	0
the	0
hippocampus	0
.	0

0ne	0
week	0
later	0
,	0
they	0
received	0
repeatedly	0
vehicles	0
(	0
saline	0
,	0
DMS0	1
,	0
saline	0
+	0
DMS0	1
)	0
,	0
scopolamine	1
(	0
2	0
microg	0
/	0
0	0
.	0
5	0
microl	0
saline	0
/	0
side	0
;	0
30	0
min	0
before	0
training	0
)	0
,	0
ritanserin	1
(	0
2	0
,	0
4	0
and	0
8	0
microg	0
/	0
0	0
.	0
5	0
microl	0
DMS0	1
/	0
side	0
;	0
20	0
min	0
before	0
training	0
)	0
and	0
scopolamine	1
(	0
2	0
microg	0
/	0
0	0
.	0
5	0
microl	0
;	0
30	0
min	0
before	0
ritanserin	1
injection	0
)	0
+	0
ritanserin	1
(	0
4	0
microg	0
/	0
0	0
.	0
5	0
microl	0
DMS0	1
)	0
through	0
cannulae	0
each	0
day	0
.	0

Animals	0
were	0
tested	0
for	0
four	0
consecutive	0
days	0
(	0
4	0
trial	0
/	0
day	0
)	0
in	0
MWM	0
during	0
which	0
the	0
position	0
of	0
hidden	0
platform	0
was	0
unchanged	0
.	0

In	0
the	0
fifth	0
day	0
,	0
the	0
platform	0
was	0
elevated	0
above	0
the	0
water	0
surface	0
in	0
another	0
position	0
to	0
evaluate	0
the	0
function	0
of	0
motor	0
,	0
motivational	0
and	0
visual	0
systems	0
.	0

The	0
results	0
showed	0
a	0
significant	0
increase	0
in	0
escape	0
latencies	0
and	0
traveled	0
distances	0
to	0
find	0
platform	0
in	0
scopolamine	1
-	0
treated	0
group	0
as	0
compared	0
to	0
saline	0
group	0
.	0

Ritanserin	1
-	0
treated	0
rats	0
(	0
4	0
microg	0
/	0
0	0
.	0
5	0
microl	0
/	0
side	0
)	0
showed	0
a	0
significant	0
decrease	0
in	0
the	0
mentioned	0
parameters	0
as	0
compared	0
to	0
DMS0	1
-	0
treated	0
group	0
.	0

However	0
,	0
scopolamine	1
and	0
ritanserin	1
co	0
-	0
administration	0
resulted	0
in	0
a	0
significant	0
decrease	0
in	0
escape	0
latencies	0
and	0
traveled	0
distances	0
as	0
compared	0
to	0
the	0
scopolamine	1
-	0
treated	0
rats	0
.	0

0ur	0
findings	0
show	0
that	0
microinjection	0
of	0
ritanserin	1
into	0
the	0
CA1	0
region	0
of	0
the	0
hippocampus	0
improves	0
the	0
scopolamine	1
-	0
induced	0
amnesia	3
.	0

PTU	1
-	0
associated	0
vasculitis	3
in	0
a	0
girl	0
with	0
Turner	3
Syndrome	4
and	0
Graves	3
'	4
disease	4
.	0

Palpable	0
purpura	3
is	0
a	0
concerning	0
clinical	0
finding	0
in	0
pediatric	0
patients	0
and	0
can	0
have	0
many	0
causes	0
,	0
including	0
infectious	0
and	0
autoimmune	0
processes	0
.	0

A	0
rare	0
cause	0
,	0
drug	0
-	0
induced	0
vasculitis	3
,	0
may	0
result	0
from	0
the	0
production	0
of	0
antineutrophil	0
cytoplasmic	0
antibodies	0
(	0
ANCAs	0
)	0
in	0
response	0
to	0
a	0
medication	0
.	0

We	0
report	0
a	0
girl	0
with	0
Turner	3
syndrome	4
and	0
Graves	3
'	4
disease	4
who	0
presented	0
with	0
palpable	0
purpuric	3
lesions	4
.	0

The	0
diagnosis	0
of	0
propylthiouracil	1
(	0
PTU	1
)	0
-	0
associated	0
vasculitis	3
was	0
made	0
by	0
observation	0
of	0
consistent	0
clinical	0
features	0
,	0
the	0
detection	0
of	0
elevated	0
ANA	0
and	0
ANCA	0
in	0
the	0
blood	0
,	0
and	0
the	0
observed	0
clinical	0
resolution	0
of	0
symptoms	0
following	0
withdrawal	0
of	0
PTU	1
.	0

Subsequent	0
treatment	0
of	0
persistent	0
hyperthyroidism	3
with	0
radioablation	0
did	0
not	0
result	0
in	0
an	0
exacerbation	0
of	0
the	0
vasculitis	3
,	0
a	0
complication	0
described	0
in	0
prior	0
case	0
reports	0
.	0

Daidzein	1
activates	0
choline	1
acetyltransferase	0
from	0
MC	0
-	0
IXC	0
cells	0
and	0
improves	0
drug	0
-	0
induced	0
amnesia	3
.	0

The	0
choline	1
acetyltransferase	0
(	0
ChAT	0
)	0
activator	0
,	0
which	0
enhances	0
cholinergic	0
transmission	0
via	0
an	0
augmentation	0
of	0
the	0
enzymatic	0
production	0
of	0
acetylcholine	1
(	0
ACh	1
)	0
,	0
is	0
an	0
important	0
factor	0
in	0
the	0
treatment	0
of	0
Alzheimer	3
'	4
s	4
disease	4
(	0
AD	3
)	0
.	0

Methanolic	0
extracts	0
from	0
Pueraria	0
thunbergiana	0
exhibited	0
an	0
activation	0
effect	0
(	0
46	0
%	0
)	0
on	0
ChAT	0
in	0
vitro	0
.	0

Via	0
the	0
sequential	0
isolation	0
of	0
Pueraria	0
thunbergiana	0
,	0
the	0
active	0
component	0
was	0
ultimately	0
identified	0
as	0
daidzein	1
(	0
4	1
'	2
,	2
7	2
-	2
dihydroxy	2
-	2
isoflavone	2
)	0
.	0

In	0
order	0
to	0
investigate	0
the	0
effects	0
of	0
daidzein	1
from	0
Pueraria	0
thunbergiana	0
on	0
scopolamine	1
-	0
induced	0
impairments	3
of	4
learning	4
and	4
memory	4
,	0
we	0
conducted	0
a	0
series	0
of	0
in	0
vivo	0
tests	0
.	0

Administration	0
of	0
daidzein	1
(	0
4	0
.	0
5	0
mg	0
/	0
kg	0
body	0
weight	0
)	0
to	0
mice	0
was	0
shown	0
significantly	0
to	0
reverse	0
scopolamine	1
-	0
induced	0
amnesia	3
,	0
according	0
to	0
the	0
results	0
of	0
a	0
Y	0
-	0
maze	0
test	0
.	0

Injections	0
of	0
scopolamine	1
into	0
mice	0
resulted	0
in	0
impaired	0
performance	0
on	0
Y	0
-	0
maze	0
tests	0
(	0
a	0
37	0
%	0
decreases	0
in	0
alternation	0
behavior	0
)	0
.	0

By	0
way	0
of	0
contrast	0
,	0
mice	0
treated	0
with	0
daidzein	1
prior	0
to	0
the	0
scopolamine	1
injections	0
were	0
noticeably	0
protected	0
from	0
this	0
performance	0
impairment	0
(	0
an	0
approximately	0
12	0
%	0
-	0
21	0
%	0
decrease	0
in	0
alternation	0
behavior	0
)	0
.	0

These	0
results	0
indicate	0
that	0
daidzein	1
might	0
play	0
a	0
role	0
in	0
acetylcholine	1
biosynthesis	0
as	0
a	0
ChAT	0
activator	0
,	0
and	0
that	0
it	0
also	0
ameliorates	0
scopolamine	1
-	0
induced	0
amnesia	3
.	0

Urinary	0
symptoms	0
and	0
quality	0
of	0
life	0
changes	0
in	0
Thai	0
women	0
with	0
overactive	3
bladder	4
after	0
tolterodine	1
treatment	0
.	0

0BJECTIVES	0
:	0
To	0
study	0
the	0
urinary	0
symptoms	0
and	0
quality	0
of	0
life	0
changes	0
in	0
Thai	0
women	0
with	0
overactive	3
bladder	4
(	0
0AB	3
)	0
after	0
tolterodine	1
treatment	0
.	0

MATERIAL	0
AND	0
METH0D	0
:	0
Thirty	0
women	0
(	0
aged	0
30	0
-	0
77	0
years	0
)	0
diagnosed	0
as	0
having	0
0AB	3
at	0
the	0
Gynecology	0
Clinic	0
,	0
King	0
Chulalongkorn	0
Memorial	0
Hospital	0
from	0
January	0
to	0
April	0
2004	0
were	0
included	0
in	0
the	0
present	0
study	0
.	0

Tolterodine	1
2	0
mg	0
,	0
twice	0
daily	0
was	0
given	0
.	0

After	0
8	0
weeks	0
treatment	0
,	0
changes	0
in	0
micturition	0
diary	0
variables	0
and	0
tolerability	0
were	0
determined	0
.	0

Short	0
form	0
36	0
(	0
SF36	0
)	0
questionaires	0
(	0
Thai	0
version	0
)	0
were	0
given	0
before	0
and	0
after	0
8	0
weeks	0
of	0
treatment	0
.	0

RESULTS	0
:	0
At	0
8	0
weeks	0
,	0
all	0
micturition	0
per	0
day	0
decreased	0
from	0
16	0
.	0

7	0
+	0
/	0
-	0
5	0
.	0

3	0
to	0
6	0
.	0

7	0
+	0
/	0
-	0
2	0
.	0
4	0
times	0
per	0
day	0
.	0

The	0
number	0
of	0
nocturia	3
episodes	0
decreased	0
from	0
5	0
.	0
4	0
+	0
/	0
-	0
4	0
.	0
2	0
to	0
1	0
.	0
1	0
+	0
/	0
-	0
1	0
.	0
0	0
times	0
per	0
night	0
.	0

The	0
most	0
common	0
side	0
effect	0
was	0
dry	3
month	4
in	0
5	0
cases	0
(	0
16	0
.	0
7	0
%	0
)	0
with	0
2	0
cases	0
reporting	0
a	0
moderate	0
degree	0
and	0
1	0
case	0
with	0
severe	0
degree	0
.	0

0nly	0
one	0
case	0
(	0
3	0
.	0
3	0
%	0
)	0
withdrew	0
from	0
the	0
present	0
study	0
due	0
to	0
a	0
severe	0
dry	3
mouth	4
.	0

The	0
SF	0
-	0
36	0
scores	0
changed	0
significantly	0
in	0
the	0
domains	0
of	0
physical	0
functioning	0
,	0
role	0
function	0
emotional	0
,	0
social	0
function	0
and	0
mental	0
heath	0
.	0

C0NCLUSI0N	0
:	0
Tolterodine	1
was	0
well	0
tolerated	0
and	0
its	0
effects	0
improved	0
the	0
quality	0
of	0
life	0
in	0
Thai	0
women	0
with	0
0AB	3
.	0

Remifentanil	1
pretreatment	0
reduces	0
myoclonus	3
after	0
etomidate	1
.	0

STUDY	0
0BJECTIVE	0
:	0
The	0
aim	0
of	0
the	0
study	0
was	0
to	0
compare	0
the	0
effect	0
of	0
pretreatment	0
with	0
remifentanil	1
1	0
microg	0
/	0
kg	0
and	0
the	0
effect	0
of	0
gender	0
on	0
the	0
incidence	0
of	0
myoclonus	3
after	0
anesthesia	0
induction	0
with	0
etomidate	1
.	0

DESIGN	0
:	0
This	0
was	0
a	0
randomized	0
,	0
double	0
-	0
blind	0
study	0
.	0

SETTING	0
:	0
The	0
study	0
was	0
conducted	0
at	0
a	0
university	0
hospital	0
.	0

PATIENTS	0
:	0
Sixty	0
patients	0
were	0
pretreated	0
in	0
a	0
randomized	0
double	0
-	0
blinded	0
fashion	0
with	0
remifentanil	1
1	0
microg	0
/	0
kg	0
or	0
placebo	0
.	0

Two	0
minutes	0
after	0
remifentanil	1
or	0
placebo	0
injection	0
,	0
etomidate	1
0	0
.	0
3	0
mg	0
/	0
kg	0
was	0
given	0
.	0

MEASUREMENTS	0
:	0
Myoclonus	3
was	0
recorded	0
with	0
a	0
scale	0
of	0
0	0
to	0
3	0
.	0

The	0
grade	0
of	0
sedation	0
(	0
none	0
,	0
mild	0
,	0
moderate	0
,	0
severe	0
)	0
,	0
nausea	3
,	0
pruritus	3
,	0
and	0
apnea	3
were	0
recorded	0
after	0
injection	0
of	0
both	0
drugs	0
.	0

MAIN	0
RESULTS	0
:	0
The	0
incidence	0
of	0
myoclonus	3
was	0
significantly	0
lower	0
in	0
the	0
remifentanil	1
group	0
(	0
6	0
.	0
7	0
%	0
)	0
than	0
in	0
the	0
placebo	0
group	0
(	0
70	0
%	0
)	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

None	0
of	0
the	0
patients	0
experienced	0
sedation	0
,	0
apnea	3
,	0
nausea	3
,	0
or	0
pruritus	3
after	0
injection	0
of	0
both	0
drugs	0
.	0

In	0
the	0
placebo	0
group	0
,	0
male	0
patients	0
were	0
associated	0
with	0
significantly	0
increased	0
incidence	0
of	0
myoclonus	3
after	0
etomidate	1
administration	0
.	0

C0NCLUSI0N	0
:	0
Pretreatment	0
with	0
remifentanil	1
1	0
microg	0
/	0
kg	0
reduced	0
myoclonus	3
after	0
etomidate	1
induction	0
without	0
side	0
effects	0
such	0
as	0
sedation	0
,	0
apnea	3
,	0
nausea	3
,	0
or	0
pruritus	3
.	0

Men	0
experience	0
increased	0
incidence	0
of	0
myoclonus	3
than	0
women	0
after	0
etomidate	1
administration	0
.	0

Memory	0
function	0
and	0
serotonin	1
transporter	0
promoter	0
gene	0
polymorphism	0
in	0
ecstasy	1
(	0
MDMA	1
)	0
users	0
.	0

Although	0
3	1
,	2
4	2
-	2
methylenedioxymethamphetamine	2
(	0
MDMA	1
or	0
ecstasy	1
)	0
has	0
been	0
shown	0
to	0
damage	0
brain	0
serotonin	1
(	0
5	1
-	2
HT	2
)	0
neurons	0
in	0
animals	0
and	0
possibly	0
humans	0
,	0
little	0
is	0
known	0
about	0
the	0
long	0
-	0
term	0
consequences	0
of	0
MDMA	1
-	0
induced	0
5	1
-	2
HT	2
neurotoxic	3
lesions	4
on	0
functions	0
in	0
which	0
5	1
-	2
HT	2
is	0
involved	0
,	0
such	0
as	0
cognitive	0
function	0
.	0

Because	0
5	1
-	2
HT	2
transporters	0
play	0
a	0
key	0
element	0
in	0
the	0
regulation	0
of	0
synaptic	0
5	1
-	2
HT	2
transmission	0
it	0
may	0
be	0
important	0
to	0
control	0
for	0
the	0
potential	0
covariance	0
effect	0
of	0
a	0
polymorphism	0
in	0
the	0
5	1
-	2
HT	2
transporter	0
promoter	0
gene	0
region	0
(	0
5	0
-	0
HTTLPR	0
)	0
when	0
studying	0
the	0
effects	0
of	0
MDMA	1
as	0
well	0
as	0
cognitive	0
functioning	0
.	0

The	0
aim	0
of	0
the	0
study	0
was	0
to	0
investigate	0
the	0
effects	0
of	0
moderate	0
and	0
heavy	0
MDMA	1
use	0
on	0
cognitive	0
function	0
,	0
as	0
well	0
as	0
the	0
effects	0
of	0
long	0
-	0
term	0
abstention	0
from	0
MDMA	1
,	0
in	0
subjects	0
genotyped	0
for	0
5	0
-	0
HTTLPR	0
.	0

A	0
second	0
aim	0
of	0
the	0
study	0
was	0
to	0
determine	0
whether	0
these	0
effects	0
differ	0
for	0
females	0
and	0
males	0
.	0

Fifteen	0
moderate	0
MDMA	1
users	0
(	0
<	0
55	0
lifetime	0
tablets	0
)	0
,	0
22	0
heavy	0
MDMA	1
+	0
users	0
(	0
>	0
55	0
lifetime	0
tablets	0
)	0
,	0
16	0
ex	0
-	0
MDMA	1
+	0
users	0
(	0
last	0
tablet	0
>	0
1	0
year	0
ago	0
)	0
and	0
13	0
controls	0
were	0
compared	0
on	0
a	0
battery	0
of	0
neuropsychological	0
tests	0
.	0

DNA	0
from	0
peripheral	0
nuclear	0
blood	0
cells	0
was	0
genotyped	0
for	0
5	0
-	0
HTTLPR	0
using	0
standard	0
polymerase	0
chain	0
reaction	0
methods	0
.	0
A	0
significant	0
group	0
effect	0
was	0
observed	0
only	0
on	0
memory	0
function	0
tasks	0
(	0
p	0
=	0
0	0
.	0
04	0
)	0
but	0
not	0
on	0
reaction	0
times	0
(	0
p	0
=	0
0	0
.	0
61	0
)	0
or	0
attention	0
/	0
executive	0
functioning	0
(	0
p	0
=	0
0	0
.	0
59	0
)	0
.	0

Heavy	0
and	0
ex	0
-	0
MDMA	1
+	0
users	0
performed	0
significantly	0
poorer	0
on	0
memory	0
tasks	0
than	0
controls	0
.	0

In	0
contrast	0
,	0
no	0
evidence	0
of	0
memory	3
impairment	4
was	0
observed	0
in	0
moderate	0
MDMA	1
users	0
.	0

No	0
significant	0
effect	0
of	0
5	0
-	0
HTTLPR	0
or	0
gender	0
was	0
observed	0
.	0

While	0
the	0
use	0
of	0
MDMA	1
in	0
quantities	0
that	0
may	0
be	0
considered	0
"	0
moderate	0
"	0
is	0
not	0
associated	0
with	0
impaired	3
memory	4
functioning	4
,	0
heavy	0
use	0
of	0
MDMA	1
use	0
may	0
lead	0
to	0
long	0
lasting	0
memory	3
impairments	4
.	0

No	0
effect	0
of	0
5	0
-	0
HTTLPR	0
or	0
gender	0
on	0
memory	0
function	0
or	0
MDMA	1
use	0
was	0
observed	0
.	0

Role	0
of	0
mangiferin	1
on	0
biochemical	0
alterations	0
and	0
antioxidant	0
status	0
in	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
in	0
rats	0
.	0

The	0
current	0
study	0
dealt	0
with	0
the	0
protective	0
role	0
of	0
mangiferin	1
,	0
a	0
polyphenol	1
from	0
Mangifera	0
indica	0
Linn	0
.	0

(	0
Anacardiaceae	0
)	0
,	0
on	0
isoproterenol	1
(	0
ISPH	1
)	0
-	0
induced	0
myocardial	3
infarction	4
(	0
MI	3
)	0
in	0
rats	0
through	0
its	0
antioxidative	0
mechanism	0
.	0

Subcutaneous	0
injection	0
of	0
ISPH	1
(	0
200	0
mg	0
/	0
kg	0
body	0
weight	0
in	0
1	0
ml	0
saline	0
)	0
to	0
rats	0
for	0
2	0
consecutive	0
days	0
caused	0
myocardial	3
damage	4
in	0
rat	0
heart	0
,	0
which	0
was	0
determined	0
by	0
the	0
increased	0
activity	0
of	0
serum	0
lactate	1
dehydrogenase	0
(	0
LDH	0
)	0
and	0
creatine	1
phosphokinase	0
isoenzymes	0
(	0
CK	0
-	0
MB	0
)	0
,	0
increased	0
uric	1
acid	2
level	0
and	0
reduced	0
plasma	0
iron	1
binding	0
capacity	0
.	0

The	0
protective	0
role	0
of	0
mangiferin	1
was	0
analyzed	0
by	0
triphenyl	1
tetrazolium	2
chloride	2
(	0
TTC	1
)	0
test	0
used	0
for	0
macroscopic	0
enzyme	0
mapping	0
assay	0
of	0
the	0
ischemic	3
myocardium	4
.	0

The	0
heart	0
tissue	0
antioxidant	0
enzymes	0
such	0
as	0
superoxide	1
dismutase	0
,	0
catalase	0
,	0
glutathione	1
peroxidase	0
,	0
glutathione	1
transferase	0
and	0
glutathione	1
reductase	0
activities	0
,	0
non	0
-	0
enzymic	0
antioxidants	0
such	0
as	0
cerruloplasmin	0
,	0
Vitamin	1
C	2
,	0
Vitamin	1
E	2
and	0
glutathione	1
levels	0
were	0
altered	0
in	0
MI	3
rats	0
.	0

Upon	0
pretreatment	0
with	0
mangiferin	1
(	0
100	0
mg	0
/	0
kg	0
body	0
weight	0
suspended	0
in	0
2	0
ml	0
of	0
dimethyl	1
sulphoxide	2
)	0
given	0
intraperitoneally	0
for	0
28	0
days	0
to	0
MI	3
rats	0
protected	0
the	0
above	0
-	0
mentioned	0
parameters	0
to	0
fall	0
from	0
the	0
normal	0
levels	0
.	0

Activities	0
of	0
heart	0
tissue	0
enzymic	0
antioxidants	0
and	0
serum	0
non	0
-	0
enzymic	0
antioxidants	0
levels	0
rose	0
significantly	0
upon	0
mangiferin	1
administration	0
as	0
compared	0
to	0
ISPH	1
-	0
induced	0
MI	3
rats	0
.	0

From	0
the	0
present	0
study	0
it	0
is	0
concluded	0
that	0
mangiferin	1
exerts	0
a	0
beneficial	0
effect	0
against	0
ISPH	1
-	0
induced	0
MI	3
due	0
to	0
its	0
antioxidant	0
potential	0
,	0
which	0
regulated	0
the	0
tissues	0
defense	0
system	0
against	0
cardiac	3
damage	4
.	0

Cardiovascular	0
risk	0
with	0
cyclooxygenase	1
inhibitors	2
:	0
general	0
problem	0
with	0
substance	0
specific	0
differences	0
?	0

Randomised	0
clinical	0
trials	0
and	0
observational	0
studies	0
have	0
shown	0
an	0
increased	0
risk	0
of	0
myocardial	3
infarction	4
,	0
stroke	3
,	0
hypertension	3
and	0
heart	3
failure	4
during	0
treatment	0
with	0
cyclooxygenase	1
inhibitors	2
.	0

Adverse	0
cardiovascular	0
effects	0
occurred	0
mainly	0
,	0
but	0
not	0
exclusively	0
,	0
in	0
patients	0
with	0
concomitant	0
risk	0
factors	0
.	0

Cyclooxygenase	1
inhibitors	2
cause	0
complex	0
changes	0
in	0
renal	0
,	0
vascular	0
and	0
cardiac	0
prostanoid	0
profiles	0
thereby	0
increasing	0
vascular	0
resistance	0
and	0
fluid	0
retention	0
.	0

The	0
incidence	0
of	0
cardiovascular	0
adverse	0
events	0
tends	0
to	0
increase	0
with	0
the	0
daily	0
dose	0
and	0
total	0
exposure	0
time	0
.	0

A	0
comparison	0
of	0
individual	0
selective	0
and	0
unselective	0
cyclooxygenase	1
inhibitors	2
suggests	0
substance	0
-	0
specific	0
differences	0
,	0
which	0
may	0
depend	0
on	0
differences	0
in	0
pharmacokinetic	0
parameters	0
or	0
inhibitory	0
potency	0
and	0
may	0
be	0
contributed	0
by	0
prostaglandin	1
-	0
independent	0
effects	0
.	0

Diagnostic	0
markers	0
such	0
as	0
N	1
-	2
terminal	2
pro	2
brain	2
natriuretic	2
peptide	2
(	0
NT	1
-	2
proBNP	2
)	0
or	0
high	0
-	0
sensitive	0
C	0
-	0
reactive	0
protein	0
might	0
help	0
in	0
the	0
early	0
identification	0
of	0
patients	0
at	0
risk	0
,	0
thus	0
avoiding	0
the	0
occurrence	0
of	0
serious	0
cardiovascular	3
toxicity	4
.	0

Pilocarpine	1
seizures	3
cause	0
age	0
-	0
dependent	0
impairment	3
in	4
auditory	4
location	4
discrimination	4
.	0

Children	0
who	0
have	0
status	3
epilepticus	4
have	0
continuous	0
or	0
rapidly	0
repeating	0
seizures	3
that	0
may	0
be	0
life	0
-	0
threatening	0
and	0
may	0
cause	0
life	0
-	0
long	0
changes	0
in	0
brain	0
and	0
behavior	0
.	0

The	0
extent	0
to	0
which	0
status	3
epilepticus	4
causes	0
deficits	3
in	4
auditory	4
discrimination	4
is	0
unknown	0
.	0

A	0
naturalistic	0
auditory	0
location	0
discrimination	0
method	0
was	0
used	0
to	0
evaluate	0
this	0
question	0
using	0
an	0
animal	0
model	0
of	0
status	3
epilepticus	4
.	0

Male	0
Sprague	0
-	0
Dawley	0
rats	0
were	0
injected	0
with	0
saline	0
on	0
postnatal	0
day	0
(	0
P	0
)	0
20	0
,	0
or	0
a	0
convulsant	0
dose	0
of	0
pilocarpine	1
on	0
P20	0
or	0
P45	0
.	0

Pilocarpine	1
on	0
either	0
day	0
induced	0
status	3
epilepticus	4
;	0
status	3
epilepticus	4
at	0
P45	0
resulted	0
in	0
CA3	0
cell	0
loss	0
and	0
spontaneous	0
seizures	3
,	0
whereas	0
P20	0
rats	0
had	0
no	0
cell	0
loss	0
or	0
spontaneous	0
seizures	3
.	0

Mature	0
rats	0
were	0
trained	0
with	0
sound	0
-	0
source	0
location	0
and	0
sound	0
-	0
silence	0
discriminations	0
.	0

Control	0
(	0
saline	0
P20	0
)	0
rats	0
acquired	0
both	0
discriminations	0
immediately	0
.	0

In	0
status	3
epilepticus	4
(	0
P20	0
)	0
rats	0
,	0
acquisition	0
of	0
the	0
sound	0
-	0
source	0
location	0
discrimination	0
was	0
moderately	0
impaired	0
.	0

Status	3
epilepticus	4
(	0
P45	0
)	0
rats	0
failed	0
to	0
acquire	0
either	0
sound	0
-	0
source	0
location	0
or	0
sound	0
-	0
silence	0
discriminations	0
.	0

Status	3
epilepticus	4
in	0
rat	0
causes	0
an	0
age	0
-	0
dependent	0
,	0
long	0
-	0
term	0
impairment	3
in	4
auditory	4
discrimination	4
.	0

This	0
impairment	0
may	0
explain	0
one	0
cause	0
of	0
impaired	3
auditory	4
location	4
discrimination	4
in	0
humans	0
.	0

Nerve	0
growth	0
factor	0
and	0
prostaglandins	1
in	0
the	0
urine	0
of	0
female	0
patients	0
with	0
overactive	3
bladder	4
.	0

PURP0SE	0
:	0
NGF	0
and	0
PGs	1
in	0
the	0
bladder	0
can	0
be	0
affected	0
by	0
pathological	0
changes	0
in	0
the	0
bladder	0
and	0
these	0
changes	0
can	0
be	0
detected	0
in	0
urine	0
.	0

We	0
investigated	0
changes	0
in	0
urinary	0
NGF	0
and	0
PGs	1
in	0
women	0
with	0
0AB	3
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
The	0
study	0
groups	0
included	0
65	0
women	0
with	0
0AB	3
and	0
20	0
without	0
bladder	0
symptoms	0
who	0
served	0
as	0
controls	0
.	0

Evaluation	0
included	0
patient	0
history	0
,	0
urinalysis	0
,	0
a	0
voiding	0
diary	0
and	0
urodynamic	0
studies	0
.	0

Urine	0
samples	0
were	0
collected	0
.	0

NGF	0
,	0
PGE2	1
,	0
PGF2alpha	1
and	0
PGI2	1
were	0
measured	0
using	0
enzyme	0
-	0
linked	0
immunosorbent	0
assay	0
and	0
compared	0
between	0
the	0
groups	0
.	0

In	0
addition	0
,	0
correlations	0
between	0
urinary	0
NGF	0
and	0
PG	1
,	0
and	0
urodynamic	0
parameters	0
in	0
patients	0
with	0
0AB	3
were	0
examined	0
.	0

RESULTS	0
:	0
Urinary	0
NGF	0
,	0
PGE2	1
and	0
PGF2alpha	1
were	0
significantly	0
increased	0
in	0
patients	0
with	0
0AB	3
compared	0
with	0
controls	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

However	0
,	0
urinary	0
PGI2	1
was	0
not	0
different	0
between	0
controls	0
and	0
patients	0
with	0
0AB	3
.	0

In	0
patients	0
with	0
0AB	3
urinary	0
PGE2	1
positively	0
correlated	0
with	0
volume	0
at	0
first	0
desire	0
to	0
void	0
and	0
maximum	0
cystometric	0
capacity	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

Urinary	0
NGF	0
,	0
PGF2alpha	1
and	0
PGI2	1
did	0
not	0
correlate	0
with	0
urodynamic	0
parameters	0
in	0
patients	0
with	0
0AB	3
.	0

C0NCLUSI0NS	0
:	0
NGF	0
and	0
PGs	1
have	0
important	0
roles	0
in	0
the	0
development	0
of	0
0AB	3
symptoms	0
in	0
female	0
patients	0
.	0

Urinary	0
levels	0
of	0
these	0
factors	0
may	0
be	0
used	0
as	0
markers	0
to	0
evaluate	0
0AB	3
symptoms	0
.	0

Definition	0
and	0
management	0
of	0
anemia	3
in	0
patients	0
infected	3
with	4
hepatitis	4
C	4
virus	4
.	0

Chronic	3
infection	4
with	4
hepatitis	4
C	4
virus	4
(	0
HCV	0
)	0
can	0
progress	0
to	0
cirrhosis	3
,	0
hepatocellular	3
carcinoma	4
,	0
and	0
end	3
-	4
stage	4
liver	4
disease	4
.	0

The	0
current	0
best	0
treatment	0
for	0
HCV	3
infection	4
is	0
combination	0
therapy	0
with	0
pegylated	0
interferon	1
and	0
ribavirin	1
.	0

Although	0
this	0
regimen	0
produces	0
sustained	0
virologic	0
responses	0
(	0
SVRs	0
)	0
in	0
approximately	0
50	0
%	0
of	0
patients	0
,	0
it	0
can	0
be	0
associated	0
with	0
a	0
potentially	0
dose	0
-	0
limiting	0
hemolytic	3
anemia	4
.	0

Hemoglobin	0
concentrations	0
decrease	0
mainly	0
as	0
a	0
result	0
of	0
ribavirin	1
-	0
induced	0
hemolysis	3
,	0
and	0
this	0
anemia	3
can	0
be	0
problematic	0
in	0
patients	0
with	0
HCV	3
infection	4
,	0
especially	0
those	0
who	0
have	0
comorbid	0
renal	3
or	4
cardiovascular	4
disorders	4
.	0

In	0
general	0
,	0
anemia	3
can	0
increase	0
the	0
risk	0
of	0
morbidity	0
and	0
mortality	0
,	0
and	0
may	0
have	0
negative	0
effects	0
on	0
cerebral	0
function	0
and	0
quality	0
of	0
life	0
.	0

Although	0
ribavirin	1
-	0
associated	0
anemia	3
can	0
be	0
reversed	0
by	0
dose	0
reduction	0
or	0
discontinuation	0
,	0
this	0
approach	0
compromises	0
outcomes	0
by	0
significantly	0
decreasing	0
SVR	0
rates	0
.	0

Recombinant	0
human	0
erythropoietin	0
has	0
been	0
used	0
to	0
manage	0
ribavirin	1
-	0
associated	0
anemia	3
but	0
has	0
other	0
potential	0
disadvantages	0
.	0

Viramidine	1
,	0
a	0
liver	0
-	0
targeting	0
prodrug	0
of	0
ribavirin	1
,	0
has	0
the	0
potential	0
to	0
maintain	0
the	0
virologic	0
efficacy	0
of	0
ribavirin	1
while	0
decreasing	0
the	0
risk	0
of	0
hemolytic	3
anemia	4
in	0
patients	0
with	0
chronic	3
hepatitis	4
C	4
.	0

Impact	0
of	0
alcohol	1
exposure	0
after	0
pregnancy	0
recognition	0
on	0
ultrasonographic	0
fetal	0
growth	0
measures	0
.	0

BACKGR0UND	0
:	0
More	0
than	0
3	0
decades	0
after	0
Jones	0
and	0
Smith	0
(	0
1973	0
)	0
reported	0
on	0
the	0
devastation	0
caused	0
by	0
alcohol	1
exposure	0
on	0
fetal	0
development	0
,	0
the	0
rates	0
of	0
heavy	0
drinking	0
during	0
pregnancy	0
remain	0
relatively	0
unchanged	0
.	0

Early	0
identification	0
of	0
fetal	0
alcohol	1
exposure	0
and	0
maternal	0
abstinence	0
led	0
to	0
better	0
infant	0
outcomes	0
.	0

This	0
study	0
examined	0
the	0
utility	0
of	0
biometry	0
for	0
detecting	0
alcohol	1
-	0
related	0
fetal	0
growth	3
impairment	4
.	0

METH0DS	0
:	0
We	0
obtained	0
fetal	0
ultrasound	0
measures	0
from	0
routine	0
ultrasound	0
examinations	0
for	0
167	0
pregnant	0
hazardous	0
drinkers	0
who	0
were	0
enrolled	0
in	0
a	0
brief	0
alcohol	1
intervention	0
study	0
.	0

The	0
fetal	0
measures	0
for	0
women	0
who	0
quit	0
after	0
learning	0
of	0
their	0
pregnancies	0
were	0
compared	0
with	0
measures	0
for	0
women	0
who	0
continued	0
some	0
drinking	0
throughout	0
the	0
course	0
of	0
their	0
pregnancies	0
.	0

Because	0
intensity	0
of	0
alcohol	1
consumption	0
is	0
associated	0
with	0
poorer	0
fetal	0
outcomes	0
,	0
separate	0
analyses	0
were	0
conducted	0
for	0
the	0
heavy	0
(	0
average	0
of	0
>	0
or	0
=	0
5	0
drinks	0
per	0
drinking	0
day	0
)	0
alcohol	1
consumers	0
.	0

Fetal	0
measures	0
from	0
the	0
heavy	0
-	0
exposed	0
fetuses	0
were	0
also	0
compared	0
with	0
measures	0
from	0
a	0
nondrinking	0
group	0
that	0
was	0
representative	0
of	0
normal	0
,	0
uncomplicated	0
pregnancies	0
from	0
our	0
clinics	0
.	0

Analyses	0
of	0
covariance	0
were	0
used	0
to	0
determine	0
whether	0
there	0
were	0
differences	0
between	0
groups	0
after	0
controlling	0
for	0
influences	0
of	0
gestational	0
age	0
and	0
drug	3
abuse	4
.	0

RESULTS	0
:	0
Nearly	0
half	0
of	0
the	0
pregnant	0
drinkers	0
abstained	0
after	0
learning	0
of	0
their	0
pregnancies	0
.	0

When	0
women	0
reportedly	0
quit	0
drinking	0
early	0
in	0
their	0
pregnancies	0
,	0
fetal	0
growth	0
measures	0
were	0
not	0
significantly	0
different	0
from	0
a	0
non	0
-	0
alcohol	1
-	0
exposed	0
group	0
,	0
regardless	0
of	0
prior	0
drinking	0
patterns	0
.	0

Any	0
alcohol	1
consumption	0
postpregnancy	0
recognition	0
among	0
the	0
heavy	0
drinkers	0
resulted	0
in	0
reduced	3
cerebellar	4
growth	4
as	0
well	0
as	0
decreased	3
cranial	4
to	4
body	4
growth	4
in	0
comparison	0
with	0
women	0
who	0
either	0
quit	0
drinking	0
or	0
who	0
were	0
nondrinkers	0
.	0

Amphetamine	1
abuse	0
was	0
predictive	0
of	0
larger	0
cranial	0
to	0
body	0
growth	0
ratios	0
.	0

C0NCLUSI0NS	0
:	0
Alterations	0
in	0
fetal	0
biometric	0
measurements	0
were	0
observed	0
among	0
the	0
heavy	0
drinkers	0
only	0
when	0
they	0
continued	0
drinking	0
after	0
becoming	0
aware	0
of	0
their	0
pregnancies	0
.	0

Although	0
the	0
reliance	0
on	0
self	0
-	0
reported	0
drinking	0
is	0
a	0
limitation	0
in	0
this	0
study	0
,	0
these	0
findings	0
support	0
the	0
benefits	0
of	0
early	0
abstinence	0
and	0
the	0
potential	0
for	0
ultrasound	0
examinations	0
in	0
the	0
detection	0
of	0
fetal	0
alcohol	1
effects	0
.	0

Ethambutol	1
-	0
associated	0
optic	3
neuropathy	4
.	0

INTR0DUCTI0N	0
:	0
Ethambutol	1
is	0
used	0
in	0
the	0
treatment	0
of	0
tuberculosis	3
,	0
which	0
is	0
still	0
prevalent	0
in	0
Southeast	0
Asia	0
,	0
and	0
can	0
be	0
associated	0
with	0
permanent	0
visual	3
loss	4
.	0

We	0
report	0
3	0
cases	0
which	0
presented	0
with	0
bitemporal	3
hemianopia	4
.	0

CLINICAL	0
PICTURE	0
:	0
Three	0
patients	0
with	0
ethambutol	1
-	0
associated	0
toxic	0
optic	3
neuropathy	4
are	0
described	0
.	0

All	0
3	0
patients	0
had	0
loss	3
of	4
central	4
visual	4
acuity	4
,	4
colour	4
vision	4
(	4
Ishihara	4
)	4
and	4
visual	4
field	4
.	0

The	0
visual	3
field	4
loss	4
had	0
a	0
bitemporal	0
flavour	0
,	0
suggesting	0
involvement	0
of	0
the	0
optic	0
chiasm	0
.	0

TREATMENT	0
:	0
Despite	0
stopping	0
ethambutol	1
on	0
diagnosis	0
,	0
visual	0
function	0
continued	0
to	0
deteriorate	0
for	0
a	0
few	0
months	0
.	0

Subsequent	0
improvement	0
was	0
mild	0
in	0
2	0
cases	0
.	0

In	0
the	0
third	0
case	0
,	0
visual	0
acuity	0
and	0
colour	0
vision	0
normalised	0
but	0
the	0
optic	0
discs	0
were	0
pale	0
.	0

0UTC0ME	0
:	0
All	0
3	0
patients	0
had	0
some	0
permanent	0
loss	3
of	4
visual	4
function	4
.	0

C0NCLUSI0NS	0
:	0
Ethambutol	1
usage	0
is	0
associated	0
with	0
permanent	0
visual	3
loss	4
and	0
should	0
be	0
avoided	0
if	0
possible	0
or	0
used	0
with	0
caution	0
and	0
proper	0
ophthalmological	0
follow	0
-	0
up	0
.	0

The	0
author	0
postulates	0
that	0
in	0
cases	0
of	0
ethambutol	1
associated	0
chiasmopathy	0
,	0
ethambutol	1
may	0
initially	0
affect	0
the	0
optic	0
nerves	0
and	0
subsequently	0
progress	0
to	0
involve	0
the	0
optic	0
chiasm	0
.	0

Possible	0
neuroleptic	3
malignant	4
syndrome	4
related	0
to	0
concomitant	0
treatment	0
with	0
paroxetine	1
and	0
alprazolam	1
.	0

A	0
74	0
-	0
year	0
-	0
old	0
man	0
with	0
depressive	3
symptoms	4
was	0
admitted	0
to	0
a	0
psychiatric	3
hospital	0
due	0
to	0
insomnia	3
,	0
loss	3
of	4
appetite	4
,	0
exhaustion	0
,	0
and	0
agitation	3
.	0

Medical	0
treatment	0
was	0
initiated	0
at	0
a	0
daily	0
dose	0
of	0
20	0
mg	0
paroxetine	1
and	0
1	0
.	0
2	0
mg	0
alprazolam	1
.	0

0n	0
the	0
10th	0
day	0
of	0
paroxetine	1
and	0
alprazolam	1
treatment	0
,	0
the	0
patient	0
exhibited	0
marked	0
psychomotor	3
retardation	4
,	0
disorientation	0
,	0
and	0
severe	0
muscle	3
rigidity	4
with	0
tremors	3
.	0

The	0
patient	0
had	0
a	0
fever	3
(	0
38	0
.	0
2	0
degrees	0
C	0
)	0
,	0
fluctuating	0
blood	0
pressure	0
(	0
between	0
165	0
/	0
90	0
and	0
130	0
/	0
70	0
mg	0
mm	0
Hg	0
)	0
,	0
and	0
severe	0
extrapyramidal	3
symptoms	4
.	0

Laboratory	0
tests	0
showed	0
an	0
elevation	0
of	0
creatine	1
phosphokinase	0
(	0
2218	0
IU	0
/	0
L	0
)	0
,	0
aspartate	1
aminotransferase	0
(	0
134	0
IU	0
/	0
L	0
)	0
,	0
alanine	1
aminotransferase	0
(	0
78	0
IU	0
/	0
L	0
)	0
,	0
and	0
BUN	0
(	0
27	0
.	0
9	0
mg	0
/	0
ml	0
)	0
levels	0
.	0

The	0
patient	0
received	0
bromocriptine	1
and	0
diazepam	1
to	0
treat	0
his	0
symptoms	0
.	0

7	0
days	0
later	0
,	0
the	0
fever	3
disappeared	0
and	0
the	0
patient	0
'	0
s	0
serum	0
CPK	0
levels	0
were	0
normalized	0
(	0
175	0
IU	0
/	0
L	0
)	0
.	0

This	0
patient	0
presented	0
with	0
symptoms	0
of	0
neuroleptic	3
malignant	4
syndrome	4
(	0
NMS	3
)	0
,	0
thus	0
demonstrating	0
that	0
NMS	3
-	0
like	0
symptoms	0
can	0
occur	0
after	0
combined	0
paroxetine	1
and	0
alprazolam	1
treatment	0
.	0

The	0
adverse	0
drug	0
reaction	0
score	0
obtained	0
by	0
the	0
Naranjo	0
algorithm	0
was	0
6	0
in	0
our	0
case	0
,	0
indicating	0
a	0
probable	0
relationship	0
between	0
the	0
patient	0
'	0
s	0
NMS	3
-	0
like	0
adverse	0
symptoms	0
and	0
the	0
combined	0
treatment	0
used	0
in	0
this	0
case	0
.	0

The	0
involvement	0
of	0
physiologic	0
and	0
environmental	0
aspects	0
specific	0
to	0
this	0
patient	0
was	0
suspected	0
.	0

Several	0
risk	0
factors	0
for	0
NMS	3
should	0
be	0
noted	0
in	0
elderly	0
depressive	3
patients	0
whose	0
symptoms	0
often	0
include	0
dehydration	3
,	0
agitation	3
,	0
malnutrition	3
,	0
and	0
exhaustion	0
.	0

Careful	0
therapeutic	0
intervention	0
is	0
necessary	0
in	0
cases	0
involving	0
elderly	0
patients	0
who	0
suffer	0
from	0
depression	3
.	0

Down	0
-	0
regulation	0
of	0
norepinephrine	1
transporter	0
function	0
induced	0
by	0
chronic	0
administration	0
of	0
desipramine	1
linking	0
to	0
the	0
alteration	0
of	0
sensitivity	0
of	0
local	0
-	0
anesthetics	0
-	0
induced	0
convulsions	3
and	0
the	0
counteraction	0
by	0
co	0
-	0
administration	0
with	0
local	0
anesthetics	0
.	0

Alterations	0
of	0
norepinephrine	1
transporter	0
(	0
NET	0
)	0
function	0
by	0
chronic	0
inhibition	0
of	0
NET	0
in	0
relation	0
to	0
sensitization	0
to	0
seizures	3
induce	0
by	0
cocaine	1
and	0
local	0
anesthetics	0
were	0
studied	0
in	0
mice	0
.	0

Daily	0
administration	0
of	0
desipramine	1
,	0
an	0
inhibitor	0
of	0
the	0
NET	0
,	0
for	0
5	0
days	0
decreased	0
[	0
(	0
3	0
)	0
H	0
]	0
norepinephrine	1
uptake	0
in	0
the	0
P2	0
fractions	0
of	0
hippocampus	0
but	0
not	0
cortex	0
,	0
striatum	0
or	0
amygdalae	0
.	0

Co	0
-	0
administration	0
of	0
lidocaine	1
,	0
bupivacaine	1
or	0
tricaine	1
with	0
desipramine	1
reversed	0
this	0
effect	0
.	0

Daily	0
treatment	0
of	0
cocaine	1
increased	0
[	0
(	0
3	0
)	0
H	0
]	0
norepinephrine	1
uptake	0
into	0
the	0
hippocampus	0
.	0

Daily	0
administration	0
of	0
desipramine	1
increased	0
the	0
incidence	0
of	0
appearance	0
of	0
lidocaine	1
-	0
induced	0
convulsions	3
and	0
decreased	0
that	0
of	0
cocaine	1
-	0
induced	0
convulsions	3
.	0

Co	0
-	0
administration	0
of	0
lidocaine	1
with	0
desipramine	1
reversed	0
the	0
changes	0
of	0
convulsive	3
activity	0
of	0
lidocaine	1
and	0
cocaine	1
induced	0
by	0
repeated	0
administration	0
of	0
desipramine	1
.	0

These	0
results	0
suggest	0
that	0
down	0
-	0
regulation	0
of	0
hippocampal	0
NET	0
induced	0
by	0
chronic	0
administration	0
of	0
desipramine	1
may	0
be	0
relevant	0
to	0
desipramine	1
-	0
induced	0
sensitization	0
of	0
lidocaine	1
convulsions	3
.	0

Inhibition	0
of	0
Na	1
(	0
+	0
)	0
channels	0
by	0
local	0
anesthetics	0
may	0
regulate	0
desipramine	1
-	0
induced	0
down	0
-	0
regulation	0
of	0
NET	0
function	0
.	0

Repeated	0
administration	0
of	0
cocaine	1
induces	0
up	0
-	0
regulation	0
of	0
hippocampal	0
NET	0
function	0
.	0

Desipramine	1
-	0
induced	0
sensitization	0
of	0
lidocaine	1
seizures	3
may	0
have	0
a	0
mechanism	0
distinct	0
from	0
kindling	0
resulting	0
from	0
repeated	0
administration	0
of	0
cocaine	1
.	0

Atorvastatin	1
prevented	0
and	0
reversed	0
dexamethasone	1
-	0
induced	0
hypertension	3
in	0
the	0
rat	0
.	0

To	0
assess	0
the	0
antioxidant	0
effects	0
of	0
atorvastatin	1
(	0
atorva	1
)	0
on	0
dexamethasone	1
(	0
dex	1
)	0
-	0
induced	0
hypertension	3
,	0
60	0
male	0
Sprague	0
-	0
Dawley	0
rats	0
were	0
treated	0
with	0
atorva	1
30	0
mg	0
/	0
kg	0
/	0
day	0
or	0
tap	0
water	0
for	0
15	0
days	0
.	0

Dex	1
increased	0
systolic	0
blood	0
pressure	0
(	0
SBP	0
)	0
from	0
109	0
+	0
/	0
-	0
1	0
.	0
8	0
to	0
135	0
+	0
/	0
-	0
0	0
.	0
6	0
mmHg	0
and	0
plasma	0
superoxide	1
(	0
5711	0
+	0
/	0
-	0
284	0
.	0
9	0
saline	0
,	0
7931	0
+	0
/	0
-	0
392	0
.	0
8	0
U	0
/	0
ml	0
dex	1
,	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

In	0
this	0
prevention	0
study	0
,	0
SBP	0
in	0
the	0
atorva	1
+	0
dex	1
group	0
was	0
increased	0
from	0
115	0
+	0
/	0
-	0
0	0
.	0
4	0
to	0
124	0
+	0
/	0
-	0
1	0
.	0
5	0
mmHg	0
,	0
but	0
this	0
was	0
significantly	0
lower	0
than	0
in	0
the	0
dex	1
-	0
only	0
group	0
(	0
P	0
'	0
<	0
0	0
.	0
05	0
)	0
.	0

Atorva	1
reversed	0
dex	1
-	0
induced	0
hypertension	3
(	0
129	0
+	0
/	0
-	0
0	0
.	0
6	0
mmHg	0
,	0
vs	0
.	0
135	0
+	0
/	0
-	0
0	0
.	0
6	0
mmHg	0
P	0
'	0
<	0
0	0
.	0
05	0
)	0
and	0
decreased	0
plasma	0
superoxide	1
(	0
7931	0
+	0
/	0
-	0
392	0
.	0
8	0
dex	1
,	0
1187	0
+	0
/	0
-	0
441	0
.	0
2	0
atorva	1
+	0
dex	1
,	0
P	0
<	0
0	0
.	0
0001	0
)	0
.	0

Plasma	0
nitrate	1
/	0
nitrite	1
(	0
N0x	0
)	0
was	0
decreased	0
in	0
dex	1
-	0
treated	0
rats	0
compared	0
to	0
saline	0
-	0
treated	0
rats	0
(	0
11	0
.	0
2	0
+	0
/	0
-	0
1	0
.	0
08	0
microm	0
,	0
15	0
.	0
3	0
+	0
/	0
-	0
1	0
.	0
17	0
microm	0
,	0
respectively	0
,	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

Atorva	1
affected	0
neither	0
plasma	0
N0x	0
nor	0
thymus	0
weight	0
.	0

Thus	0
,	0
atorvastatin	1
prevented	0
and	0
reversed	0
dexamethasone	1
-	0
induced	0
hypertension	3
in	0
the	0
rat	0
.	0

Peripheral	3
neuropathy	4
caused	0
by	0
high	0
-	0
dose	0
cytosine	1
arabinoside	2
treatment	0
in	0
a	0
patient	0
with	0
acute	3
myeloid	4
leukemia	4
.	0

The	0
central	0
nervous	0
system	0
toxicity	3
of	0
high	0
-	0
dose	0
cytosine	1
arabinoside	2
is	0
well	0
recognized	0
,	0
but	0
the	0
toxicity	3
of	0
cytosine	1
arabinoside	2
in	0
the	0
peripheral	0
nervous	0
system	0
has	0
been	0
infrequently	0
reported	0
.	0

A	0
49	0
-	0
year	0
-	0
old	0
Japanese	0
man	0
was	0
diagnosed	0
with	0
acute	3
myeloid	4
leukemia	4
.	0

After	0
he	0
achieved	0
complete	0
remission	0
,	0
he	0
received	0
high	0
-	0
dose	0
cytosine	1
arabinoside	2
treatment	0
(	0
2	0
g	0
/	0
m2	0
twice	0
a	0
day	0
for	0
5	0
days	0
;	0
total	0
,	0
20	0
g	0
/	0
m2	0
)	0
as	0
consolidation	0
therapy	0
.	0

The	0
first	0
course	0
of	0
high	0
-	0
dose	0
cytosine	1
arabinoside	2
resulted	0
in	0
no	0
unusual	0
symptoms	0
,	0
but	0
on	0
day	0
21	0
of	0
the	0
second	0
course	0
of	0
treatment	0
,	0
the	0
patient	0
complained	0
of	0
numbness	3
in	0
his	0
right	0
foot	0
.	0

Electromyogram	0
and	0
nerve	0
-	0
conduction	0
studies	0
showed	0
peripheral	3
neuropathy	4
in	0
both	0
peroneal	0
nerves	0
.	0

This	0
neuropathy	3
was	0
gradually	0
resolving	0
;	0
however	0
,	0
after	0
the	0
patient	0
received	0
allogeneic	0
bone	0
marrow	0
transplantation	0
,	0
the	0
symptoms	0
worsened	0
,	0
with	0
the	0
development	0
of	0
graft	3
-	4
versus	4
-	4
host	4
disease	4
,	0
and	0
the	0
symptoms	0
subsequently	0
responded	0
to	0
methylprednisolone	1
.	0

Although	0
the	0
mechanisms	0
of	0
peripheral	3
neuropathy	4
are	0
still	0
unclear	0
,	0
high	0
-	0
dose	0
cytosine	1
arabinoside	2
is	0
a	0
therapy	0
that	0
is	0
potentially	0
toxic	0
to	0
the	0
peripheral	0
nervous	0
system	0
,	0
and	0
auto	0
/	0
alloimmunity	0
may	0
play	0
an	0
important	0
role	0
in	0
these	0
mechanisms	0
.	0

Effect	0
of	0
alpha	1
-	2
tocopherol	2
and	0
deferoxamine	1
on	0
methamphetamine	1
-	0
induced	0
neurotoxicity	3
.	0

Methamphetamine	1
(	0
MA	1
)	0
-	0
induced	0
dopaminergic	0
neurotoxicity	3
is	0
believed	0
to	0
be	0
associated	0
with	0
the	0
increased	0
formation	0
of	0
free	0
radicals	0
.	0

This	0
study	0
examined	0
the	0
effect	0
of	0
alpha	1
-	2
tocopherol	2
(	0
alpha	1
-	2
TC	2
)	0
,	0
a	0
scavenger	0
of	0
reactive	0
oxygen	1
species	0
,	0
and	0
deferoxamine	1
(	0
DF0	1
)	0
,	0
an	0
iron	1
chelator	0
,	0
on	0
the	0
MA	1
-	0
induced	0
neurotoxicity	3
.	0

Male	0
rats	0
were	0
treated	0
with	0
MA	1
(	0
10	0
mg	0
/	0
kg	0
,	0
every	0
2	0
h	0
for	0
four	0
injections	0
)	0
.	0

The	0
rat	0
received	0
either	0
alpha	1
-	2
TC	2
(	0
20	0
mg	0
/	0
kg	0
)	0
intraperitoneally	0
for	0
3	0
days	0
and	0
30	0
min	0
prior	0
to	0
MA	1
administration	0
or	0
DF0	1
(	0
50	0
mg	0
/	0
kg	0
)	0
subcutaneously	0
30	0
min	0
before	0
MA	1
administration	0
.	0

The	0
concentrations	0
of	0
dopamine	1
(	0
DA	1
)	0
,	0
serotonin	1
and	0
their	0
metabolites	0
decreased	0
significantly	0
after	0
MA	1
administration	0
,	0
which	0
was	0
inhibited	0
by	0
the	0
alpha	1
-	2
TC	2
and	0
DF0	1
pretreatment	0
.	0

alpha	1
-	2
TC	2
and	0
DF0	1
attenuated	0
the	0
MA	1
-	0
induced	0
hyperthermia	3
as	0
well	0
as	0
the	0
alterations	0
in	0
the	0
locomotor	0
activity	0
.	0

The	0
level	0
of	0
lipid	0
peroxidation	0
was	0
higher	0
and	0
the	0
reduced	0
glutathione	1
concentration	0
was	0
lower	0
in	0
the	0
MA	1
-	0
treated	0
rats	0
.	0

These	0
changes	0
were	0
significantly	0
attenuated	0
by	0
alpha	1
-	2
TC	2
and	0
DF0	1
.	0

This	0
suggests	0
that	0
alpha	1
-	2
TC	2
and	0
DF0	1
ameliorate	0
the	0
MA	1
-	0
induced	0
neuronal	3
damage	4
by	0
decreasing	0
the	0
level	0
of	0
oxidative	0
stress	0
.	0

Blockade	0
of	0
both	0
D	0
-	0
1	0
and	0
D	0
-	0
2	0
dopamine	1
receptors	0
may	0
induce	0
catalepsy	3
in	0
mice	0
.	0

1	0
.	0

The	0
catalepsy	3
induced	0
by	0
dopamine	1
antagonists	0
has	0
been	0
tested	0
and	0
the	0
possible	0
dopamine	1
subtypes	0
involved	0
in	0
catalepsy	3
was	0
determined	0
.	0

2	0
.	0

Dopamine	1
antagonist	0
fluphenazine	1
,	0
D	0
-	0
1	0
antagonist	0
SCH	1
23390	2
or	0
D	0
-	0
2	0
antagonist	0
sulpiride	1
induced	0
catalepsy	3
.	0

The	0
effect	0
of	0
fluphenazine	1
and	0
sulpiride	1
was	0
dose	0
-	0
dependent	0
.	0

Combination	0
of	0
SCH	1
23390	2
with	0
sulpiride	1
did	0
not	0
induce	0
catalepsy	3
potentiation	0
.	0

3	0
.	0

D	0
-	0
1	0
agonist	0
SKF	1
38393	2
or	0
D	0
-	0
2	0
agonist	0
quinpirole	1
decreased	0
the	0
catalepsy	3
induced	0
by	0
fluphenazine	1
,	0
SCH	1
23390	2
or	0
sulpiride	1
.	0

4	0
.	0

Combination	0
of	0
SKF	1
38393	2
with	0
quinpirole	1
did	0
not	0
cause	0
potentiated	0
inhibitory	0
effect	0
on	0
catalepsy	3
induced	0
by	0
dopamine	1
antagonists	0
.	0

5	0
.	0

The	0
data	0
may	0
indicate	0
that	0
although	0
D	0
-	0
2	0
receptor	0
blockade	0
is	0
involved	0
in	0
catalepsy	3
,	0
the	0
D	0
-	0
1	0
receptor	0
may	0
plan	0
a	0
role	0
.	0

Sustained	0
clinical	0
improvement	0
of	0
a	0
patient	0
with	0
decompensated	0
hepatitis	3
B	4
virus	0
-	0
related	0
cirrhosis	3
after	0
treatment	0
with	0
lamivudine	1
monotherapy	0
.	0

Hepatitis	3
B	4
virus	4
(	4
HBV	4
)	4
infection	4
,	0
which	0
causes	0
liver	3
cirrhosis	4
and	0
hepatocellular	3
carcinoma	4
,	0
remains	0
a	0
major	0
health	0
problem	0
in	0
Asian	0
countries	0
.	0

Recent	0
development	0
of	0
vaccine	0
for	0
prevention	0
is	0
reported	0
to	0
be	0
successful	0
in	0
reducing	0
the	0
size	0
of	0
chronically	0
infected	0
carriers	0
,	0
although	0
the	0
standard	0
medical	0
therapies	0
have	0
not	0
been	0
established	0
up	0
to	0
now	0
.	0

In	0
this	0
report	0
,	0
we	0
encountered	0
a	0
patient	0
with	0
decompensated	0
HBV	0
-	0
related	0
cirrhosis	3
who	0
exhibited	0
the	0
dramatic	0
improvements	0
after	0
antiviral	0
therapy	0
.	0

The	0
patient	0
was	0
a	0
50	0
-	0
year	0
-	0
old	0
woman	0
.	0

Previous	0
conventional	0
medical	0
treatments	0
were	0
not	0
effective	0
for	0
this	0
patient	0
,	0
thus	0
this	0
patient	0
had	0
been	0
referred	0
to	0
our	0
hospital	0
.	0

However	0
,	0
the	0
administration	0
of	0
lamivudine	1
,	0
a	0
reverse	0
transcriptase	0
inhibitor	0
,	0
for	0
23	0
months	0
dramatically	0
improved	0
her	0
liver	0
severity	0
.	0

During	0
this	0
period	0
,	0
no	0
drug	0
resistant	0
mutant	0
HBV	0
emerged	0
,	0
and	0
the	0
serum	0
HBV	0
-	0
DNA	0
level	0
was	0
continuously	0
suppressed	0
.	0

These	0
virological	0
responses	0
were	0
also	0
maintained	0
even	0
after	0
the	0
antiviral	0
therapy	0
was	0
discontinued	0
.	0

Moreover	0
,	0
both	0
hepatitis	1
B	2
surface	2
antigen	2
and	2
e	2
antigen	2
were	0
observed	0
to	0
have	0
disappeared	0
in	0
this	0
patient	0
.	0

The	0
administration	0
of	0
lamivudine	1
to	0
patients	0
with	0
HBV	0
-	0
related	0
cirrhosis	3
,	0
like	0
our	0
present	0
case	0
,	0
should	0
be	0
considered	0
as	0
an	0
initial	0
medical	0
therapeutic	0
option	0
,	0
especially	0
in	0
countries	0
where	0
liver	0
transplantation	0
is	0
not	0
reliably	0
available	0
.	0

Antiarrhythmic	0
effects	0
of	0
optical	0
isomers	0
of	0
cibenzoline	1
on	0
canine	0
ventricular	3
arrhythmias	4
.	0

Antiarrhythmic	0
effects	0
of	0
(	0
+	0
)	0
-	0
cibenzoline	1
and	0
(	0
-	0
)	0
-	0
cibenzoline	1
were	0
examined	0
using	0
two	0
canine	0
ventricular	3
arrhythmia	4
models	0
.	0

Digitalis	1
arrhythmia	3
,	0
which	0
is	0
suppressed	0
by	0
Na	1
channel	0
blockers	0
,	0
was	0
induced	0
by	0
intermittent	0
intravenous	0
(	0
i	0
.	0
v	0
.	0
)	0
injection	0
of	0
ouabain	1
in	0
pentobarbital	1
-	0
anesthetized	0
dogs	0
.	0

Adrenaline	3
arrhythmia	4
,	0
which	0
is	0
suppressed	0
by	0
Ca	1
channel	0
blockers	0
,	0
was	0
induced	0
by	0
adrenaline	1
infusion	0
in	0
halothane	1
-	0
anesthetized	0
dogs	0
.	0

Ten	0
and	0
5	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
(	0
+	0
)	0
-	0
cibenzoline	1
suppressed	0
digitalis	1
-	0
and	0
adrenaline	1
-	0
induced	0
arrhythmias	3
,	0
respectively	0
.	0

The	0
minimum	0
effective	0
plasma	0
concentrations	0
of	0
(	0
+	0
)	0
-	0
cibenzoline	1
for	0
digitalis	1
-	0
and	0
adrenaline	1
-	0
induced	0
arrhythmias	3
were	0
1	0
.	0
4	0
+	0
/	0
-	0
0	0
.	0
4	0
and	0
2	0
.	0
0	0
+	0
/	0
-	0
0	0
.	0
6	0
micrograms	0
/	0
ml	0
,	0
respectively	0
(	0
mean	0
+	0
/	0
-	0
SD	0
,	0
n	0
=	0
6	0
)	0
.	0

A	0
lower	0
dose	0
of	0
1	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
of	0
(	0
-	0
)	0
-	0
cibenzoline	1
suppressed	0
the	0
digitalis	1
-	0
induced	0
arrhythmia	3
,	0
whereas	0
5	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
was	0
needed	0
to	0
suppress	0
adrenaline	1
-	0
induced	0
arrhythmias	3
.	0

The	0
minimum	0
effective	0
plasma	0
concentrations	0
of	0
(	0
-	0
)	0
-	0
cibenzoline	1
for	0
digitalis	1
-	0
and	0
adrenaline	1
-	0
induced	0
arrhythmia	3
were	0
0	0
.	0
06	0
+	0
/	0
-	0
0	0
.	0
04	0
and	0
0	0
.	0
7	0
+	0
/	0
-	0
0	0
.	0
1	0
micrograms	0
/	0
ml	0
,	0
respectively	0
(	0
mean	0
+	0
/	0
-	0
SD	0
,	0
n	0
=	0
6	0
)	0
.	0

The	0
stronger	0
antiarrhythmic	0
effect	0
of	0
(	0
-	0
)	0
-	0
cibenzoline	1
indicates	0
that	0
(	0
-	0
)	0
-	0
isomer	0
may	0
have	0
an	0
effect	0
nearly	0
5	0
-	0
20	0
times	0
stronger	0
in	0
suppressing	0
Na	1
channels	0
,	0
but	0
effects	0
of	0
both	0
drugs	0
on	0
Ca	1
channels	0
may	0
be	0
almost	0
equipotent	0
.	0

Passage	0
of	0
mannitol	1
into	0
the	0
brain	0
around	0
gliomas	3
:	0
a	0
potential	0
cause	0
of	0
rebound	0
phenomenon	0
.	0

A	0
study	0
on	0
21	0
patients	0
.	0

AIM	0
:	0
Widespread	0
use	0
of	0
mannitol	1
to	0
reduce	0
brain	3
edema	4
and	0
lower	0
elevated	3
ICP	4
in	0
brain	3
tumor	4
patients	0
continues	0
to	0
be	0
afflicted	0
by	0
the	0
so	0
-	0
called	0
rebound	0
phenomenon	0
.	0

Leakage	0
of	0
mannitol	1
into	0
the	0
brain	0
parenchyma	0
through	0
an	0
altered	0
BBB	0
and	0
secondary	0
reversal	0
of	0
osmotic	0
gradient	0
is	0
considered	0
the	0
major	0
cause	0
of	0
rebound	0
.	0

This	0
has	0
only	0
been	0
demonstrated	0
experimentally	0
in	0
animals	0
.	0

As	0
a	0
contribution	0
to	0
this	0
issue	0
we	0
decided	0
to	0
research	0
the	0
possible	0
passage	0
of	0
mannitol	1
into	0
the	0
brain	0
after	0
administration	0
to	0
21	0
brain	3
tumor	4
patients	0
.	0

METH0DS	0
:	0
Mannitol	1
(	0
18	0
%	0
solution	0
;	0
1	0
g	0
/	0
kg	0
)	0
was	0
administered	0
as	0
a	0
bolus	0
to	0
patients	0
(	0
ten	0
had	0
malignant	3
glioma	4
,	0
seven	0
brain	0
metastases	3
and	0
four	0
meningioma	3
)	0
about	0
30	0
minutes	0
before	0
craniotomy	0
.	0

During	0
resection	0
,	0
a	0
sample	0
of	0
the	0
surrounding	0
edematous	3
white	0
matter	0
was	0
taken	0
at	0
the	0
same	0
time	0
as	0
a	0
10	0
ml	0
venous	0
blood	0
sample	0
.	0

Mannitol	1
concentrations	0
were	0
measured	0
in	0
plasma	0
and	0
white	0
matter	0
by	0
a	0
modified	0
version	0
of	0
the	0
enzyme	0
assay	0
of	0
Blonquist	0
et	0
al	0
.	0

RESULTS	0
:	0
In	0
most	0
glioma	3
patients	0
,	0
mannitol	1
concentrations	0
in	0
white	0
matter	0
were	0
2	0
to	0
6	0
times	0
higher	0
than	0
in	0
plasma	0
(	0
mean	0
3	0
.	0
5	0
times	0
)	0
.	0

In	0
meningioma	3
and	0
metastases	3
patients	0
plasma	0
concentrations	0
of	0
mannitol	1
were	0
higher	0
than	0
white	0
matter	0
concentrations	0
except	0
in	0
three	0
cases	0
with	0
infiltration	0
by	0
neoplastic	0
cells	0
.	0

C0NCLUSI0NS	0
:	0
The	0
results	0
of	0
our	0
study	0
show	0
that	0
even	0
after	0
a	0
single	0
bolus	0
,	0
mannitol	1
may	0
leak	0
through	0
the	0
altered	0
BBB	0
near	0
gliomas	3
,	0
reversing	0
the	0
initial	0
plasma	0
-	0
to	0
-	0
blood	0
osmotic	0
gradient	0
,	0
aggravating	0
peritumoral	0
edema	3
and	0
promoting	0
rebound	0
of	0
ICP	0
.	0

Placebo	0
-	0
level	0
incidence	0
of	0
extrapyramidal	3
symptoms	4
(	0
EPS	3
)	0
with	0
quetiapine	1
in	0
controlled	0
studies	0
of	0
patients	0
with	0
bipolar	3
mania	4
.	0

0BJECTIVES	0
:	0
To	0
evaluate	0
extrapyramidal	3
symptoms	4
(	0
EPS	3
)	0
,	0
including	0
akathisia	3
,	0
with	0
quetiapine	1
in	0
patients	0
with	0
bipolar	3
mania	4
.	0

METH0DS	0
:	0
Data	0
were	0
analyzed	0
from	0
four	0
similarly	0
designed	0
,	0
randomized	0
,	0
double	0
-	0
blind	0
,	0
3	0
-	0
to	0
12	0
-	0
week	0
studies	0
.	0

Two	0
studies	0
evaluated	0
quetiapine	1
monotherapy	0
(	0
up	0
to	0
800	0
mg	0
/	0
day	0
)	0
(	0
n	0
=	0
209	0
)	0
versus	0
placebo	0
(	0
n	0
=	0
198	0
)	0
,	0
with	0
lithium	1
or	0
haloperidol	1
monotherapy	0
as	0
respective	0
active	0
controls	0
.	0

Two	0
studies	0
evaluated	0
quetiapine	1
(	0
up	0
to	0
800	0
mg	0
/	0
day	0
)	0
in	0
combination	0
with	0
a	0
mood	0
stabilizer	0
(	0
lithium	1
or	0
divalproex	1
,	0
QTP	1
+	0
Li	1
/	0
DVP	1
)	0
(	0
n	0
=	0
196	0
)	0
compared	0
to	0
placebo	0
and	0
mood	0
stabilizer	0
(	0
PB0	0
+	0
Li	1
/	0
DVP	1
)	0
(	0
n	0
=	0
203	0
)	0
.	0

Extrapyramidal	3
symptoms	4
were	0
evaluated	0
using	0
the	0
Simpson	0
-	0
Angus	0
Scale	0
(	0
SAS	0
)	0
,	0
the	0
Barnes	0
Akathisia	0
Rating	0
Scale	0
(	0
BARS	0
)	0
,	0
adverse	0
event	0
reports	0
and	0
anticholinergic	0
drug	0
usage	0
.	0

RESULTS	0
:	0
The	0
incidence	0
of	0
EPS	3
-	0
related	0
adverse	0
events	0
,	0
including	0
akathisia	3
,	0
was	0
no	0
different	0
with	0
quetiapine	1
monotherapy	0
(	0
12	0
.	0
9	0
%	0
)	0
than	0
with	0
placebo	0
(	0
13	0
.	0
1	0
%	0
)	0
.	0

Similarly	0
,	0
EPS	3
-	0
related	0
adverse	0
events	0
with	0
QTP	1
+	0
Li	1
/	0
DVP	1
(	0
21	0
.	0
4	0
%	0
)	0
were	0
no	0
different	0
than	0
with	0
PB0	0
+	0
Li	1
/	0
DVP	1
(	0
19	0
.	0
2	0
%	0
)	0
.	0

Adverse	0
events	0
related	0
to	0
EPS	3
occurred	0
in	0
59	0
.	0
6	0
%	0
of	0
patients	0
treated	0
with	0
haloperidol	1
(	0
n	0
=	0
99	0
)	0
monotherapy	0
,	0
whereas	0
26	0
.	0
5	0
%	0
of	0
patients	0
treated	0
with	0
lithium	1
(	0
n	0
=	0
98	0
)	0
monotherapy	0
experienced	0
adverse	0
events	0
related	0
to	0
EPS	3
.	0

The	0
incidence	0
of	0
akathisia	3
was	0
low	0
and	0
similar	0
with	0
quetiapine	1
monotherapy	0
(	0
3	0
.	0
3	0
%	0
)	0
and	0
placebo	0
(	0
6	0
.	0
1	0
%	0
)	0
,	0
and	0
with	0
QTP	1
+	0
Li	1
/	0
DVP	1
(	0
3	0
.	0
6	0
%	0
)	0
and	0
PB0	0
+	0
Li	1
/	0
DVP	1
(	0
4	0
.	0
9	0
%	0
)	0
.	0

Lithium	1
was	0
associated	0
with	0
a	0
significantly	0
higher	0
incidence	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
of	0
tremor	3
(	0
18	0
.	0
4	0
%	0
)	0
than	0
quetiapine	1
(	0
5	0
.	0
6	0
%	0
)	0
;	0
cerebellar	0
tremor	3
,	0
which	0
is	0
a	0
known	0
adverse	0
effect	0
of	0
lithium	1
,	0
may	0
have	0
contributed	0
to	0
the	0
elevated	0
rate	0
of	0
tremor	3
in	0
patients	0
receiving	0
lithium	1
therapy	0
.	0

Haloperidol	1
induced	0
a	0
significantly	0
higher	0
incidence	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
of	0
akathisia	3
(	0
33	0
.	0
3	0
%	0
versus	0
5	0
.	0
9	0
%	0
)	0
,	0
tremor	3
(	0
30	0
.	0
3	0
%	0
versus	0
7	0
.	0
8	0
%	0
)	0
,	0
and	0
extrapyramidal	3
syndrome	4
(	0
35	0
.	0
4	0
%	0
versus	0
5	0
.	0
9	0
%	0
)	0
than	0
quetiapine	1
.	0

No	0
significant	0
differences	0
were	0
observed	0
between	0
quetiapine	1
and	0
placebo	0
on	0
SAS	0
and	0
BARS	0
scores	0
.	0

Anticholinergic	0
use	0
was	0
low	0
and	0
similar	0
with	0
quetiapine	1
or	0
placebo	0
.	0

C0NCLUSI0NS	0
:	0
In	0
bipolar	3
mania	4
,	0
the	0
incidence	0
of	0
EPS	3
,	0
including	0
akathisia	3
,	0
with	0
quetiapine	1
therapy	0
is	0
similar	0
to	0
that	0
with	0
placebo	0
.	0

Is	0
phenytoin	1
administration	0
safe	0
in	0
a	0
hypothermic	3
child	0
?	0

A	0
male	0
neonate	0
with	0
a	0
Chiari	3
malformation	4
and	0
a	0
leaking	0
myelomeningocoele	0
underwent	0
ventriculoperitoneal	0
shunt	0
insertion	0
followed	0
by	0
repair	0
of	0
myelomeningocoele	0
.	0

During	0
anaesthesia	0
and	0
surgery	0
,	0
he	0
inadvertently	0
became	0
moderately	0
hypothermic	3
.	0

Intravenous	0
phenytoin	1
was	0
administered	0
during	0
the	0
later	0
part	0
of	0
the	0
surgery	0
for	0
seizure	3
prophylaxis	0
.	0

Following	0
phenytoin	1
administration	0
,	0
the	0
patient	0
developed	0
acute	0
severe	0
bradycardia	3
,	0
refractory	0
to	0
atropine	1
and	0
adrenaline	1
.	0

The	0
cardiac	0
depressant	0
actions	0
of	0
phenytoin	1
and	0
hypothermia	3
can	0
be	0
additive	0
.	0

Administration	0
of	0
phenytoin	1
in	0
the	0
presence	0
of	0
hypothermia	3
may	0
lead	0
to	0
an	0
adverse	0
cardiac	0
event	0
in	0
children	0
.	0

As	0
phenytoin	1
is	0
a	0
commonly	0
used	0
drug	0
,	0
clinicians	0
need	0
to	0
be	0
aware	0
of	0
this	0
interaction	0
.	0

Valproate	1
-	0
induced	0
chorea	3
and	0
encephalopathy	3
in	0
atypical	0
nonketotic	3
hyperglycinemia	4
.	0

Nonketotic	3
hyperglycinemia	4
is	0
a	0
disorder	3
of	4
amino	4
acid	4
metabolism	4
in	0
which	0
a	0
defect	0
in	0
the	0
glycine	1
cleavage	0
system	0
leads	0
to	0
an	0
accumulation	0
of	0
glycine	1
in	0
the	0
brain	0
and	0
other	0
body	0
compartments	0
.	0

In	0
the	0
classical	0
form	0
it	0
presents	0
as	0
neonatal	0
apnea	3
,	0
intractable	0
seizures	3
,	0
and	0
hypotonia	3
,	0
followed	0
by	0
significant	0
psychomotor	3
retardation	4
.	0

An	0
important	0
subset	0
of	0
children	0
with	0
nonketotic	3
hyperglycinemia	4
are	0
atypical	0
variants	0
who	0
present	0
in	0
a	0
heterogeneous	0
manner	0
.	0

This	0
report	0
describes	0
a	0
patient	0
with	0
mild	0
language	3
delay	4
and	0
mental	3
retardation	4
,	0
who	0
was	0
found	0
to	0
have	0
nonketotic	3
hyperglycinemia	4
following	0
her	0
presentation	0
with	0
acute	0
encephalopathy	3
and	0
chorea	3
shortly	0
after	0
initiation	0
of	0
valproate	1
therapy	0
.	0

Delayed	0
institution	0
of	0
hypertension	3
during	0
focal	0
cerebral	3
ischemia	4
:	0
effect	0
on	0
brain	3
edema	4
.	0

The	0
effect	0
of	0
induced	0
hypertension	3
instituted	0
after	0
a	0
2	0
-	0
h	0
delay	0
following	0
middle	3
cerebral	4
artery	4
occlusion	4
(	0
MCA0	3
)	0
on	0
brain	3
edema	4
formation	0
and	0
histochemical	0
injury	0
was	0
studied	0
.	0

Under	0
isoflurane	1
anesthesia	0
,	0
the	0
MCA	0
of	0
14	0
spontaneously	0
hypertensive	3
rats	0
was	0
occluded	0
.	0

In	0
the	0
control	0
group	0
(	0
n	0
=	0
7	0
)	0
,	0
the	0
mean	0
arterial	0
pressure	0
(	0
MAP	0
)	0
was	0
not	0
manipulated	0
.	0

In	0
the	0
hypertensive	3
group	0
(	0
n	0
=	0
7	0
)	0
,	0
the	0
MAP	0
was	0
elevated	0
by	0
25	0
-	0
30	0
mm	0
Hg	0
beginning	0
2	0
h	0
after	0
MCA0	3
.	0

Four	0
hours	0
after	0
MCA0	3
,	0
the	0
rats	0
were	0
killed	0
and	0
the	0
brains	0
harvested	0
.	0

The	0
brains	0
were	0
sectioned	0
along	0
coronal	0
planes	0
spanning	0
the	0
distribution	0
of	0
ischemia	3
produced	0
by	0
MCA0	3
.	0

Specific	0
gravity	0
(	0
SG	0
)	0
was	0
determined	0
in	0
the	0
subcortex	0
and	0
in	0
two	0
sites	0
in	0
the	0
cortex	0
(	0
core	0
and	0
periphery	0
of	0
the	0
ischemic	3
territory	0
)	0
.	0

The	0
extent	0
of	0
neuronal	3
injury	4
was	0
determined	0
by	0
2	1
,	2
3	2
,	2
5	2
-	2
triphenyltetrazolium	2
staining	0
.	0

In	0
the	0
ischemic	3
core	0
,	0
there	0
was	0
no	0
difference	0
in	0
SG	0
in	0
the	0
subcortex	0
and	0
cortex	0
in	0
the	0
two	0
groups	0
.	0

In	0
the	0
periphery	0
of	0
the	0
ischemic	3
territory	0
,	0
SG	0
in	0
the	0
cortex	0
was	0
greater	0
(	0
less	0
edema	3
accumulation	0
)	0
in	0
the	0
hypertensive	3
group	0
(	0
1	0
.	0
041	0
+	0
/	0
-	0
0	0
.	0
001	0
vs	0
1	0
.	0
039	0
+	0
/	0
-	0
0	0
.	0
001	0
,	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

The	0
area	0
of	0
histochemical	0
injury	0
(	0
as	0
a	0
percent	0
of	0
the	0
cross	0
-	0
sectional	0
area	0
of	0
the	0
hemisphere	0
)	0
was	0
less	0
in	0
the	0
hypertensive	3
group	0
(	0
33	0
+	0
/	0
-	0
3	0
%	0
vs	0
21	0
+	0
/	0
-	0
2	0
%	0
,	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

The	0
data	0
indicate	0
that	0
phenylephrine	1
-	0
induced	0
hypertension	3
instituted	0
2	0
h	0
after	0
MCA0	3
does	0
not	0
aggravate	0
edema	3
in	0
the	0
ischemic	3
core	0
,	0
that	0
it	0
improves	0
edema	3
in	0
the	0
periphery	0
of	0
the	0
ischemic	3
territory	0
,	0
and	0
that	0
it	0
reduces	0
the	0
area	0
of	0
histochemical	0
neuronal	3
dysfunction	4
.	0

Behavioral	0
effects	0
of	0
pubertal	0
anabolic	0
androgenic	0
steroid	1
exposure	0
in	0
male	0
rats	0
with	0
low	0
serotonin	1
.	0

The	0
goal	0
of	0
this	0
study	0
was	0
to	0
assess	0
the	0
interactive	0
effects	0
of	0
chronic	0
anabolic	0
androgenic	0
steroid	1
(	0
AAS	0
)	0
exposure	0
and	0
brain	0
serotonin	1
(	0
5	1
-	2
hydroxytryptamine	2
,	0
5	1
-	2
HT	2
)	0
depletion	0
on	0
behavior	0
of	0
pubertal	0
male	0
rats	0
.	0

Serotonin	1
was	0
depleted	0
beginning	0
on	0
postnatal	0
day	0
26	0
with	0
parachlorophenylalanine	1
(	0
PCPA	1
100	0
mg	0
/	0
kg	0
,	0
every	0
other	0
day	0
)	0
;	0
controls	0
received	0
saline	0
.	0

At	0
puberty	0
(	0
P40	0
)	0
,	0
half	0
the	0
PCPA	1
-	0
treated	0
rats	0
and	0
half	0
the	0
saline	0
-	0
treated	0
rats	0
began	0
treatment	0
with	0
testosterone	1
(	0
T	1
,	0
5	0
mg	0
/	0
kg	0
,	0
5	0
days	0
/	0
week	0
)	0
.	0

Behavioral	0
measures	0
included	0
locomotion	0
,	0
irritability	3
,	0
copulation	0
,	0
partner	0
preference	0
,	0
and	0
aggression	3
.	0

Animals	0
were	0
tested	0
for	0
aggression	3
in	0
their	0
home	0
cage	0
,	0
both	0
with	0
and	0
without	0
physical	0
provocation	0
(	0
mild	0
tail	0
pinch	0
)	0
.	0

Brain	0
levels	0
of	0
5	1
-	2
HT	2
and	0
its	0
metabolite	0
,	0
5	1
-	2
hydroxyindoleacetic	2
acid	2
(	0
5	1
-	2
HIAA	2
)	0
,	0
were	0
determined	0
using	0
HPLC	0
.	0

PCPA	1
significantly	0
and	0
substantially	0
depleted	0
5	1
-	2
HT	2
and	0
5	1
-	2
HIAA	2
in	0
all	0
brain	0
regions	0
examined	0
.	0

Chronic	0
T	1
treatment	0
significantly	0
decreased	0
5	1
-	2
HT	2
and	0
5	1
-	2
HIAA	2
in	0
certain	0
brain	0
areas	0
,	0
but	0
to	0
a	0
much	0
lesser	0
extent	0
than	0
PCPA	1
.	0

Chronic	0
exposure	0
to	0
PCPA	1
alone	0
significantly	0
decreased	0
locomotor	0
activity	0
and	0
increased	0
irritability	3
but	0
had	0
no	0
effect	0
on	0
sexual	0
behavior	0
,	0
partner	0
preference	0
,	0
or	0
aggression	3
.	0

T	1
alone	0
had	0
no	0
effect	0
on	0
locomotion	0
,	0
irritability	3
,	0
or	0
sexual	0
behavior	0
but	0
increased	0
partner	0
preference	0
and	0
aggression	3
.	0

The	0
most	0
striking	0
effect	0
of	0
combining	0
T	1
+	0
PCPA	1
was	0
a	0
significant	0
increase	0
in	0
attack	0
frequency	0
as	0
well	0
as	0
a	0
significant	0
decrease	0
in	0
the	0
latency	0
to	0
attack	0
,	0
particularly	0
following	0
physical	0
provocation	0
.	0

Based	0
on	0
these	0
data	0
,	0
it	0
can	0
be	0
speculated	0
that	0
pubertal	0
AAS	0
users	0
with	0
low	0
central	0
5	1
-	2
HT	2
may	0
be	0
especially	0
prone	0
to	0
exhibit	0
aggressive	3
behavior	4
.	0

Effects	0
of	0
UMB24	1
and	0
(	0
+	0
/	0
-	0
)	0
-	0
SM	1
21	2
,	0
putative	0
sigma2	0
-	0
preferring	0
antagonists	0
,	0
on	0
behavioral	0
toxic	0
and	0
stimulant	0
effects	0
of	0
cocaine	1
in	0
mice	0
.	0

Earlier	0
studies	0
have	0
demonstrated	0
that	0
antagonism	0
of	0
sigma1	0
receptors	0
attenuates	0
the	0
convulsive	3
,	0
lethal	0
,	0
locomotor	0
stimulatory	0
and	0
rewarding	0
actions	0
of	0
cocaine	1
in	0
mice	0
.	0

In	0
contrast	0
,	0
the	0
contribution	0
of	0
sigma2	0
receptors	0
is	0
unclear	0
because	0
experimental	0
tools	0
to	0
selectively	0
target	0
this	0
subtype	0
are	0
unavailable	0
.	0

To	0
begin	0
addressing	0
this	0
need	0
,	0
we	0
characterized	0
UMB24	1
(	0
1	1
-	2
(	2
2	2
-	2
phenethyl	2
)	2
-	2
4	2
-	2
(	2
2	2
-	2
pyridyl	2
)	2
-	2
piperazine	2
)	0
and	0
(	0
+	0
/	0
-	0
)	0
-	0
SM	1
21	2
(	0
3alpha	1
-	2
tropanyl	2
-	2
2	2
-	2
(	2
4	2
-	2
chorophenoxy	2
)	2
butyrate	2
)	0
in	0
receptor	0
binding	0
and	0
behavioral	0
studies	0
.	0

Receptor	0
binding	0
studies	0
confirmed	0
that	0
UMB24	1
and	0
(	0
+	0
/	0
-	0
)	0
-	0
SM	1
21	2
display	0
preferential	0
affinity	0
for	0
sigma2	0
over	0
sigma1	0
receptors	0
.	0

In	0
behavioral	0
studies	0
,	0
pretreatment	0
of	0
Swiss	0
Webster	0
mice	0
with	0
UMB24	1
or	0
(	0
+	0
/	0
-	0
)	0
-	0
SM	1
21	2
significantly	0
attenuated	0
cocaine	1
-	0
induced	0
convulsions	3
and	0
locomotor	0
activity	0
,	0
but	0
not	0
lethality	0
.	0

When	0
administered	0
alone	0
,	0
(	0
+	0
/	0
-	0
)	0
-	0
SM	1
21	2
produced	0
no	0
significant	0
effects	0
compared	0
to	0
control	0
injections	0
of	0
saline	0
,	0
but	0
UMB24	1
had	0
locomotor	0
depressant	0
actions	0
.	0

Together	0
,	0
the	0
data	0
suggest	0
that	0
sigma2	0
receptor	0
antagonists	0
have	0
the	0
potential	0
to	0
attenuate	0
some	0
of	0
the	0
behavioral	0
effects	0
of	0
cocaine	1
,	0
and	0
further	0
development	0
of	0
more	0
selective	0
,	0
high	0
affinity	0
ligands	0
are	0
warranted	0
.	0

Cardiac	3
arrest	4
in	0
a	0
child	0
with	0
cerebral	3
palsy	4
undergoing	0
sevoflurane	1
induction	0
of	0
anesthesia	0
after	0
preoperative	0
clonidine	1
.	0

Clonidine	1
is	0
a	0
frequently	0
administered	0
alpha2	0
-	0
adrenergic	0
agonist	0
which	0
can	0
decrease	0
heart	0
rate	0
and	0
blood	0
pressure	0
.	0

We	0
present	0
a	0
case	0
of	0
a	0
5	0
-	0
year	0
-	0
old	0
child	0
with	0
cerebral	3
palsy	4
and	0
seizure	3
disorder	4
,	0
receiving	0
clonidine	1
for	0
restlessness	3
,	0
who	0
presented	0
for	0
placement	0
of	0
a	0
baclofen	1
pump	0
.	0

Without	0
the	0
knowledge	0
of	0
the	0
medical	0
personnel	0
,	0
the	0
patient	0
'	0
s	0
mother	0
administered	0
three	0
doses	0
of	0
clonidine	1
during	0
the	0
evening	0
before	0
and	0
morning	0
of	0
surgery	0
to	0
reduce	0
anxiety	3
.	0

During	0
induction	0
of	0
anesthesia	0
,	0
the	0
patient	0
developed	0
bradycardia	3
and	0
hypotension	3
requiring	0
cardiac	0
resuscitation	0
.	0

There	0
are	0
no	0
previous	0
reports	0
of	0
clonidine	1
-	0
associated	0
cardiac	3
arrest	4
in	0
a	0
child	0
undergoing	0
induction	0
of	0
anesthesia	0
.	0

Angiotensin	0
-	0
converting	0
enzyme	0
(	0
ACE	0
)	0
inhibitor	0
-	0
associated	0
angioedema	3
of	0
the	0
stomach	0
and	0
small	0
intestine	0
:	0
a	0
case	0
report	0
.	0

This	0
is	0
a	0
case	0
report	0
on	0
a	0
45	0
-	0
year	0
old	0
African	0
-	0
American	0
female	0
with	0
newly	0
diagnosed	0
hypertension	3
,	0
who	0
was	0
started	0
on	0
a	0
combination	0
pill	0
of	0
amlodipine	1
/	0
benazapril	1
10	0
/	0
5	0
mg	0
.	0

The	0
very	0
next	0
day	0
,	0
she	0
presented	0
at	0
the	0
emergency	0
room	0
(	0
ER	0
)	0
with	0
abdominal	3
pain	4
,	0
nausea	3
and	0
vomiting	3
.	0

Physical	0
exam	0
,	0
complete	0
metabolic	0
panel	0
,	0
and	0
hemogram	0
were	0
in	0
the	0
normal	0
range	0
.	0

She	0
was	0
discharged	0
from	0
the	0
ER	0
after	0
a	0
few	0
hours	0
of	0
treatment	0
with	0
fluid	0
and	0
analgesics	0
.	0

However	0
,	0
she	0
returned	0
to	0
the	0
ER	0
the	0
next	0
day	0
with	0
the	0
same	0
complaints	0
.	0

This	0
time	0
the	0
physical	0
exam	0
was	0
significant	0
for	0
a	0
distended	0
abdomen	0
with	0
dullness	0
to	0
percussion	0
.	0

CT	0
scan	0
of	0
the	0
abdomen	0
revealed	0
markedly	0
thickened	0
antrum	0
of	0
the	0
stomach	0
,	0
duodenum	0
and	0
jejunum	0
,	0
along	0
with	0
fluid	0
in	0
the	0
abdominal	0
and	0
pelvic	0
cavity	0
.	0

Angiotensin	0
-	0
converting	0
enzyme	0
inhibitor	0
(	0
ACEI	0
)	0
-	0
induced	0
angioedema	3
was	0
suspected	0
,	0
and	0
anti	0
-	0
hypertensive	3
medications	0
were	0
discontinued	0
.	0

Her	0
symptoms	0
improved	0
within	0
the	0
next	0
24	0
hours	0
,	0
and	0
repeat	0
CT	0
after	0
72	0
hours	0
revealed	0
marked	0
improvement	0
in	0
stomach	0
and	0
small	0
bowel	0
thickening	0
and	0
resolution	0
of	0
ascites	3
.	0

The	0
recognition	0
of	0
angiotensin	1
-	0
converting	0
enzyme	0
(	0
ACE	0
)	0
and	0
angiotensin	1
receptor	0
blocker	0
(	0
ARB	0
)	0
intestinal	3
angioedema	4
constitutes	0
a	0
challenge	0
to	0
primary	0
care	0
physicians	0
,	0
internists	0
,	0
emergency	0
room	0
personal	0
and	0
surgeons	0
.	0

Carbamazepine	1
-	0
induced	0
cardiac	3
dysfunction	4
.	0

Characterization	0
of	0
two	0
distinct	0
clinical	0
syndromes	0
.	0

A	0
patient	0
with	0
sinus	0
bradycardia	3
and	0
atrioventricular	3
block	4
,	0
induced	0
by	0
carbamazepine	1
,	0
prompted	0
an	0
extensive	0
literature	0
review	0
of	0
all	0
previously	0
reported	0
cases	0
.	0

From	0
the	0
analysis	0
of	0
these	0
cases	0
,	0
two	0
distinct	0
forms	0
of	0
carbamazepine	1
-	0
associated	0
cardiac	3
dysfunction	4
emerged	0
.	0

0ne	0
patient	0
group	0
developed	0
sinus	3
tachycardias	4
in	0
the	0
setting	0
of	0
a	0
massive	0
carbamazepine	1
overdose	3
.	0

The	0
second	0
group	0
consisted	0
almost	0
exclusively	0
of	0
elderly	0
women	0
who	0
developed	0
potentially	0
life	0
-	0
threatening	0
bradyarrhythmias	3
or	0
atrioventricular	3
conduction	4
delay	4
,	0
associated	0
with	0
either	0
therapeutic	0
or	0
modestly	0
elevated	0
carbamazepine	1
serum	0
levels	0
.	0

Because	0
carbamazepine	1
is	0
widely	0
used	0
in	0
the	0
treatment	0
of	0
many	0
neurologic	0
and	0
psychiatric	3
conditions	0
,	0
the	0
recognition	0
of	0
the	0
latter	0
syndrome	0
has	0
important	0
implications	0
for	0
the	0
use	0
of	0
this	0
drug	0
in	0
elderly	0
patients	0
.	0

Detection	0
of	0
abnormal	0
cardiac	0
adrenergic	0
neuron	0
activity	0
in	0
adriamycin	1
-	0
induced	0
cardiomyopathy	3
with	0
iodine	1
-	2
125	2
-	2
metaiodobenzylguanidine	2
.	0

Radiolabeled	1
metaiodobenzylguanidine	2
(	0
MIBG	1
)	0
,	0
an	0
analog	0
of	0
norepinephrine	1
(	0
NE	1
)	0
,	0
serves	0
as	0
an	0
index	0
of	0
adrenergic	0
neuron	0
integrity	0
and	0
function	0
.	0

Using	0
a	0
rat	0
model	0
of	0
adriamycin	1
-	0
induced	0
cardiomyopathy	3
,	0
we	0
tested	0
the	0
hypothesis	0
that	0
abnormal	0
cardiac	0
adrenergic	0
neuron	0
activity	0
may	0
appear	0
and	0
be	0
exacerbated	0
dose	0
-	0
dependently	0
in	0
adriamycin	1
cardiomyopathy	3
.	0

The	0
degree	0
of	0
vacuolar	3
degeneration	4
of	4
myocardial	4
cells	4
was	0
analyzed	0
in	0
relation	0
to	0
the	0
duration	0
of	0
adriamycin	1
treatment	0
(	0
2	0
mg	0
/	0
kg	0
,	0
once	0
a	0
week	0
)	0
.	0

There	0
were	0
no	0
abnormalities	0
or	0
only	0
isolated	0
degeneration	0
in	0
the	0
1	0
-	0
or	0
2	0
-	0
wk	0
treatment	0
groups	0
,	0
isolated	0
or	0
scattered	0
degeneration	0
in	0
half	0
of	0
the	0
3	0
-	0
wk	0
group	0
,	0
frequent	0
scattered	0
degeneration	0
in	0
the	0
4	0
-	0
wk	0
group	0
,	0
scattered	0
or	0
focal	0
degeneration	0
in	0
the	0
5	0
-	0
wk	0
group	0
,	0
and	0
extensive	0
degeneration	0
in	0
the	0
8	0
-	0
wk	0
group	0
.	0

Myocardial	0
accumulation	0
of	0
[	0
125I	0
]	0
MIBG	1
4	0
hr	0
after	0
intravenous	0
injection	0
did	0
not	0
differ	0
between	0
the	0
controls	0
and	0
the	0
groups	0
treated	0
3	0
wk	0
or	0
less	0
.	0

However	0
,	0
the	0
4	0
-	0
wk	0
group	0
had	0
a	0
slightly	0
lower	0
accumulation	0
in	0
the	0
right	0
ventricular	0
wall	0
(	0
82	0
%	0
of	0
the	0
control	0
)	0
and	0
significantly	0
lower	0
accumulation	0
in	0
the	0
left	0
ventricular	0
wall	0
(	0
about	0
66	0
%	0
of	0
the	0
control	0
:	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

In	0
the	0
5	0
-	0
wk	0
group	0
,	0
MIBG	1
accumulation	0
in	0
the	0
right	0
and	0
left	0
ventricular	0
wall	0
was	0
35	0
%	0
and	0
27	0
%	0
of	0
that	0
in	0
controls	0
,	0
respectively	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
.	0

In	0
the	0
8	0
-	0
wk	0
group	0
,	0
MIBG	1
accumulation	0
in	0
the	0
right	0
and	0
left	0
ventricular	0
wall	0
was	0
18	0
%	0
and	0
14	0
%	0
of	0
that	0
in	0
controls	0
,	0
respectively	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
.	0

Thus	0
,	0
MIBG	1
accumulation	0
in	0
the	0
myocardium	0
decreased	0
in	0
an	0
adriamycin	1
dose	0
-	0
dependent	0
manner	0
.	0

The	0
appearance	0
of	0
impaired	0
cardiac	0
adrenergic	0
neuron	0
activity	0
in	0
the	0
presence	0
of	0
slight	0
myocardial	3
impairment	4
(	0
scattered	0
or	0
focal	0
vacuolar	3
degeneration	4
)	0
indicates	0
that	0
MIBG	1
scintigraphy	0
may	0
be	0
a	0
useful	0
method	0
for	0
detection	0
of	0
adriamycin	1
-	0
induced	0
cardiomyopathy	3
.	0

Syncope	3
and	0
QT	3
prolongation	4
among	0
patients	0
treated	0
with	0
methadone	1
for	0
heroin	1
dependence	0
in	0
the	0
city	0
of	0
Copenhagen	0
.	0

BACKGR0UND	0
:	0
Methadone	1
is	0
prescribed	0
to	0
heroin	1
addicts	0
to	0
decrease	0
illicit	0
opioid	0
use	0
.	0

Prolongation	0
of	0
the	0
QT	0
interval	0
in	0
the	0
ECG	0
of	0
patients	0
with	0
torsade	3
de	4
pointes	4
(	0
TdP	3
)	0
has	0
been	0
reported	0
in	0
methadone	1
users	0
.	0

As	0
heroin	1
addicts	0
sometimes	0
faint	0
while	0
using	0
illicit	0
drugs	0
,	0
doctors	0
might	0
attribute	0
too	0
many	0
episodes	0
of	0
syncope	3
to	0
illicit	0
drug	0
use	0
and	0
thereby	0
underestimate	0
the	0
incidence	0
of	0
TdP	3
in	0
this	0
special	0
population	0
,	0
and	0
the	0
high	0
mortality	0
in	0
this	0
population	0
may	0
,	0
in	0
part	0
,	0
be	0
caused	0
by	0
the	0
proarrhythmic	0
effect	0
of	0
methadone	1
.	0

METH0DS	0
:	0
In	0
this	0
cross	0
-	0
sectional	0
study	0
interview	0
,	0
ECGs	0
and	0
blood	0
samples	0
were	0
collected	0
in	0
a	0
population	0
of	0
adult	0
heroin	1
addicts	0
treated	0
with	0
methadone	1
or	0
buprenorphine	1
on	0
a	0
daily	0
basis	0
.	0

0f	0
the	0
patients	0
at	0
the	0
Drug	0
Addiction	0
Service	0
in	0
the	0
municipal	0
of	0
Copenhagen	0
,	0
450	0
(	0
approximately	0
52	0
%	0
)	0
were	0
included	0
.	0

The	0
QT	0
interval	0
was	0
estimated	0
from	0
12	0
lead	0
ECGs	0
.	0

All	0
participants	0
were	0
interviewed	0
about	0
any	0
experience	0
of	0
syncope	3
.	0

The	0
association	0
between	0
opioid	0
dose	0
and	0
QT	0
,	0
and	0
methadone	1
dose	0
and	0
reporting	0
of	0
syncope	3
was	0
assessed	0
using	0
multivariate	0
linear	0
regression	0
and	0
logistic	0
regression	0
,	0
respectively	0
.	0

RESULTS	0
:	0
Methadone	1
dose	0
was	0
associated	0
with	0
longer	0
QT	0
interval	0
of	0
0	0
.	0
140	0
ms	0
/	0
mg	0
(	0
p	0
=	0
0	0
.	0
002	0
)	0
.	0

No	0
association	0
between	0
buprenorphine	1
and	0
QTc	0
was	0
found	0
.	0

Among	0
the	0
subjects	0
treated	0
with	0
methadone	1
,	0
28	0
%	0
men	0
and	0
32	0
%	0
women	0
had	0
prolonged	3
QTc	4
interval	4
.	0

None	0
of	0
the	0
subjects	0
treated	0
with	0
buprenorphine	1
had	0
QTc	0
interval	0
>	0
0	0
.	0
440	0
s	0
(	0
(	0
1	0
/	0
2	0
)	0
)	0
.	0

A	0
50	0
mg	0
higher	0
methadone	1
dose	0
was	0
associated	0
with	0
a	0
1	0
.	0
2	0
(	0
95	0
%	0
CI	0
1	0
.	0
1	0
to	0
1	0
.	0
4	0
)	0
times	0
higher	0
odds	0
for	0
syncope	3
.	0

C0NCLUSI0NS	0
:	0
Methadone	1
is	0
associated	0
with	0
QT	3
prolongation	4
and	0
higher	0
reporting	0
of	0
syncope	3
in	0
a	0
population	0
of	0
heroin	1
addicts	0
.	0

Neuroleptic	3
malignant	4
syndrome	4
induced	0
by	0
ziprasidone	1
on	0
the	0
second	0
day	0
of	0
treatment	0
.	0

Neuroleptic	3
malignant	4
syndrome	4
(	0
NMS	3
)	0
is	0
the	0
rarest	0
and	0
most	0
serious	0
of	0
the	0
neuroleptic	0
-	0
induced	0
movement	3
disorders	4
.	0

We	0
describe	0
a	0
case	0
of	0
neuroleptic	3
malignant	4
syndrome	4
(	0
NMS	3
)	0
associated	0
with	0
the	0
use	0
of	0
ziprasidone	1
.	0

Although	0
conventional	0
neuroleptics	0
are	0
more	0
frequently	0
associated	0
with	0
NMS	3
,	0
atypical	0
antipsychotic	0
drugs	0
like	0
ziprasidone	1
may	0
also	0
be	0
a	0
cause	0
.	0

The	0
patient	0
is	0
a	0
24	0
-	0
year	0
-	0
old	0
male	0
with	0
a	0
history	0
of	0
schizophrenia	3
who	0
developed	0
signs	0
and	0
symptoms	0
of	0
NMS	3
after	0
2	0
days	0
of	0
treatment	0
with	0
an	0
80	0
-	0
mg	0
/	0
day	0
dose	0
of	0
orally	0
administrated	0
ziprasidone	1
.	0

This	0
case	0
is	0
the	0
earliest	0
(	0
second	0
day	0
of	0
treatment	0
)	0
NMS	3
due	0
to	0
ziprasidone	1
reported	0
in	0
the	0
literature	0
.	0

Peripheral	0
iron	1
dextran	2
induced	0
degeneration	3
of	4
dopaminergic	4
neurons	4
in	0
rat	0
substantia	0
nigra	0
.	0

Iron	1
accumulation	0
is	0
considered	0
to	0
be	0
involved	0
in	0
the	0
pathogenesis	0
of	0
Parkinson	3
'	4
s	4
disease	4
.	0

To	0
demonstrate	0
the	0
relationship	0
between	0
peripheral	0
iron	1
overload	0
and	0
dopaminergic	0
neuron	0
loss	0
in	0
rat	0
substantia	0
nigra	0
(	0
SN	0
)	0
,	0
in	0
the	0
present	0
study	0
we	0
used	0
fast	0
cyclic	0
voltammetry	0
,	0
tyrosine	1
hydroxylase	0
(	0
TH	0
)	0
immunohistochemistry	0
,	0
Perls	0
'	0
iron	1
staining	0
,	0
and	0
high	0
performance	0
liquid	0
chromatography	0
-	0
electrochemical	0
detection	0
to	0
study	0
the	0
degeneration	3
of	4
dopaminergic	4
neurons	4
and	0
increased	0
iron	1
content	0
in	0
the	0
SN	0
of	0
iron	1
dextran	2
overloaded	0
animals	0
.	0

The	0
findings	0
showed	0
that	0
peripheral	0
iron	1
dextran	2
overload	0
increased	0
the	0
iron	1
staining	0
positive	0
cells	0
and	0
reduced	0
the	0
number	0
of	0
TH	0
-	0
immunoreactive	0
neurons	0
in	0
the	0
SN	0
.	0

As	0
a	0
result	0
,	0
dopamine	1
release	0
and	0
content	0
,	0
as	0
well	0
as	0
its	0
metabolites	0
contents	0
were	0
decreased	0
in	0
caudate	0
putamen	0
.	0

Even	0
more	0
dramatic	0
changes	0
were	0
found	0
in	0
chronic	0
overload	0
group	0
.	0

These	0
results	0
suggest	0
that	0
peripheral	0
iron	1
dextran	2
can	0
increase	0
the	0
iron	1
level	0
in	0
the	0
SN	0
,	0
where	0
excessive	0
iron	1
causes	0
the	0
degeneration	3
of	4
dopaminergic	4
neurons	4
.	0

The	0
chronic	0
iron	1
overload	0
may	0
be	0
more	0
destructive	0
to	0
dopaminergic	0
neurons	0
than	0
the	0
acute	0
iron	1
overload	0
.	0

Attenuated	0
disruption	0
of	0
prepulse	0
inhibition	0
by	0
dopaminergic	0
stimulation	0
after	0
maternal	0
deprivation	0
and	0
adolescent	0
corticosterone	1
treatment	0
in	0
rats	0
.	0

The	0
development	0
of	0
schizophrenia	3
may	0
include	0
an	0
early	0
neurodevelopmental	0
stress	0
component	0
which	0
increases	0
vulnerability	0
to	0
later	0
stressful	0
life	0
events	0
,	0
in	0
combination	0
leading	0
to	0
overt	0
disease	0
.	0

We	0
investigated	0
the	0
effect	0
of	0
an	0
early	0
stress	0
,	0
in	0
the	0
form	0
of	0
maternal	0
deprivation	0
,	0
combined	0
with	0
a	0
later	0
stress	0
,	0
simulated	0
by	0
chronic	0
periadolescent	0
corticosterone	1
treatment	0
,	0
on	0
behaviour	0
in	0
rats	0
.	0

Acute	0
treatment	0
with	0
apomorphine	1
caused	0
disruption	0
of	0
prepulse	0
inhibition	0
(	0
PPI	0
)	0
in	0
controls	0
and	0
in	0
rats	0
that	0
had	0
undergone	0
either	0
maternal	0
deprivation	0
or	0
corticosterone	1
treatment	0
,	0
but	0
was	0
surprisingly	0
absent	0
in	0
rats	0
that	0
had	0
undergone	0
the	0
combined	0
early	0
and	0
late	0
stress	0
.	0

Amphetamine	1
treatment	0
significantly	0
disrupted	0
PPI	0
in	0
both	0
non	0
-	0
deprived	0
groups	0
,	0
but	0
was	0
absent	0
in	0
both	0
maternally	0
deprived	0
groups	0
.	0

The	0
serotonin	1
-	0
1A	0
receptor	0
agonist	0
,	0
8	1
-	2
0H	2
-	2
DPAT	2
,	0
induced	0
a	0
significant	0
disruption	0
of	0
PPI	0
in	0
all	0
groups	0
.	0

Amphetamine	1
-	0
induced	0
locomotor	3
hyperactivity	4
was	0
similar	0
in	0
all	0
groups	0
.	0

These	0
results	0
show	0
an	0
inhibitory	0
interaction	0
of	0
early	0
stress	0
,	0
caused	0
by	0
maternal	0
deprivation	0
,	0
combined	0
with	0
'	0
adolescent	0
'	0
stress	0
,	0
simulated	0
by	0
corticosterone	1
treatment	0
,	0
on	0
dopaminergic	0
regulation	0
of	0
PPI	0
.	0

The	0
altered	0
effects	0
of	0
apomorphine	1
and	0
amphetamine	1
could	0
indicate	0
differential	0
changes	0
in	0
dopamine	1
receptor	0
signalling	0
leading	0
to	0
functional	0
desensitisation	0
,	0
or	0
altered	0
modulation	0
of	0
sensory	0
gating	0
in	0
the	0
nucleus	0
accumbens	0
by	0
limbic	0
structures	0
such	0
as	0
the	0
hippocampus	0
.	0

An	0
extremely	0
rare	0
case	0
of	0
delusional	3
parasitosis	4
in	0
a	0
chronic	3
hepatitis	4
C	4
patient	0
during	0
pegylated	1
interferon	2
alpha	2
-	2
2b	2
and	0
ribavirin	1
treatment	0
.	0

During	0
treatment	0
of	0
chronic	3
hepatitis	4
C	4
patients	0
with	0
interferon	0
and	0
ribavirin	1
,	0
a	0
lot	0
of	0
side	0
effects	0
are	0
described	0
.	0

Twenty	0
-	0
three	0
percent	0
to	0
44	0
%	0
of	0
patients	0
develop	0
depression	3
.	0

A	0
minority	0
of	0
patients	0
evolve	0
to	0
psychosis	3
.	0

To	0
the	0
best	0
of	0
our	0
knowledge	0
,	0
no	0
cases	0
of	0
psychogenic	3
parasitosis	4
occurring	0
during	0
interferon	0
therapy	0
have	0
been	0
described	0
in	0
the	0
literature	0
.	0

We	0
present	0
a	0
49	0
-	0
year	0
-	0
old	0
woman	0
who	0
developed	0
a	0
delusional	3
parasitosis	4
during	0
treatment	0
with	0
pegylated	1
interferon	2
alpha	2
-	2
2b	2
weekly	0
and	0
ribavirin	1
.	0

She	0
complained	0
of	0
seeing	0
parasites	0
and	0
the	0
larvae	0
of	0
fleas	0
in	0
her	0
stools	0
.	0

This	0
could	0
not	0
be	0
confirmed	0
by	0
any	0
technical	0
examination	0
.	0

All	0
the	0
complaints	0
disappeared	0
after	0
stopping	0
pegylated	1
interferon	2
alpha	2
-	2
2b	2
and	0
reappeared	0
after	0
restarting	0
it	0
.	0

She	0
had	0
a	0
complete	0
sustained	0
viral	0
response	0
.	0

Hepatonecrosis	3
and	0
cholangitis	3
related	0
to	0
long	0
-	0
term	0
phenobarbital	1
therapy	0
:	0
an	0
autopsy	0
report	0
of	0
two	0
patients	0
.	0

Phenobarbital	1
(	0
PB	1
)	0
has	0
a	0
reputation	0
for	0
safety	0
,	0
and	0
it	0
is	0
commonly	0
believed	0
that	0
PB	1
-	0
related	0
increases	0
in	0
serum	0
aminotransferase	0
levels	0
do	0
not	0
indicate	0
or	0
predict	0
the	0
development	0
of	0
significant	0
chronic	0
liver	3
disease	4
.	0

Here	0
we	0
report	0
of	0
two	0
adult	0
patients	0
with	0
a	0
long	0
history	0
of	0
epilepsy	3
treated	0
with	0
PB	1
who	0
died	0
suddenly	0
:	0
one	0
as	0
consequence	0
of	0
cardiac	3
arrest	4
,	0
the	0
other	0
of	0
acute	0
bronchopneumonia	3
.	0

At	0
autopsy	0
,	0
analysis	0
of	0
liver	0
parenchyma	0
revealed	0
rich	0
portal	0
inflammatory	0
infiltrate	0
,	0
which	0
consisted	0
of	0
mixed	0
eosinophil	0
and	0
monocyte	0
cells	0
,	0
associated	0
with	0
several	0
foci	0
of	0
necrosis	3
surrounded	0
by	0
a	0
hard	0
ring	0
of	0
non	0
-	0
specific	0
granulomatous	0
tissue	0
.	0

Inflammatory	0
reactions	0
of	0
internal	0
and	0
external	0
hepatic	0
biliary	0
ducts	0
were	0
also	0
seen	0
.	0

0ur	0
findings	0
illustrate	0
that	0
PB	1
may	0
be	0
associated	0
with	0
chronic	0
liver	3
damage	4
,	0
which	0
may	0
lead	0
to	0
more	0
serious	0
and	0
deleterious	0
consequences	0
.	0

For	0
this	0
reason	0
,	0
each	0
clinician	0
should	0
recognize	0
this	0
entity	0
in	0
the	0
differential	0
diagnosis	0
of	0
PB	1
-	0
related	0
asymptomatic	0
chronic	3
hepatic	4
enzyme	4
dysfunction	4
.	0

Delayed	0
leukoencephalopathy	3
with	0
stroke	3
-	0
like	0
presentation	0
in	0
chemotherapy	0
recipients	0
.	0

BACKGR0UND	0
:	0
A	0
transient	0
leukoencephalopathy	3
mimicking	0
cerebrovascular	3
accident	4
has	0
been	0
described	0
as	0
a	0
complication	0
of	0
chemotherapy	0
,	0
most	0
commonly	0
in	0
recipients	0
of	0
intrathecal	0
methotrexate	1
for	0
childhood	0
leukaemia	3
.	0

Recently	0
published	0
neuroimaging	0
data	0
suggest	0
a	0
common	0
pathophysiology	0
associated	0
with	0
a	0
variety	0
of	0
chemotherapy	0
agents	0
and	0
modes	0
of	0
administration	0
.	0

METH0DS	0
:	0
We	0
reviewed	0
the	0
medical	0
literature	0
for	0
single	0
reports	0
and	0
case	0
series	0
of	0
patients	0
presenting	0
with	0
stroke	3
-	0
like	0
episodes	0
while	0
receiving	0
systemic	0
or	0
intrathecal	0
chemotherapy	0
.	0

We	0
only	0
included	0
studies	0
providing	0
detailed	0
neuroimaging	0
data	0
.	0

Patients	0
with	0
cerebrovascular	3
accidents	4
were	0
excluded	0
.	0

RESULTS	0
:	0
We	0
identified	0
27	0
reports	0
of	0
toxic	0
leukoencephalopathy	3
in	0
patients	0
treated	0
with	0
methotrexate	1
(	0
intrathecal	0
,	0
systemic	0
)	0
,	0
5	1
-	2
fluorouracil	2
and	0
its	0
derivative	0
carmofur	1
,	0
and	0
capecitabine	1
.	0

Diffusion	0
weighted	0
imaging	0
(	0
DWI	0
)	0
of	0
all	0
patients	0
revealed	0
well	0
demarcated	0
hyperintense	0
lesions	3
within	4
the	4
subcortical	4
white	4
matter	4
of	0
the	0
cerebral	0
hemispheres	0
and	0
the	0
corpus	0
callosum	0
,	0
corresponding	0
to	0
areas	0
of	0
decreased	0
proton	0
diffusion	0
on	0
apparent	0
diffusion	0
coefficient	0
(	0
ADC	0
)	0
maps	0
(	0
available	0
in	0
21	0
/	0
27	0
patients	0
)	0
.	0

Lesions	0
exceeded	0
the	0
confines	0
of	0
adjacent	0
vascular	0
territories	0
.	0

Complete	0
resolution	0
of	0
symptoms	0
within	0
1	0
-	0
4	0
days	0
was	0
accompanied	0
by	0
normalisation	0
of	0
ADC	0
abnormalities	0
.	0

However	0
,	0
fluid	0
attenuated	0
inversion	0
recovery	0
(	0
FLAIR	0
)	0
sequences	0
frequently	0
revealed	0
persistent	0
white	3
matter	4
abnormalities	4
.	0

C0NCLUSI0NS	0
:	0
Several	0
pathophysiological	0
models	0
of	0
delayed	0
leukoencephalopathy	3
after	0
exposure	0
to	0
intrathecal	0
or	0
systemic	0
chemotherapy	0
have	0
been	0
proposed	0
.	0

DWI	0
findings	0
in	0
this	0
cohort	0
are	0
indicative	0
of	0
cytotoxic	3
oedema	4
within	4
cerebral	4
white	4
matter	4
and	0
lend	0
support	0
to	0
an	0
at	0
least	0
partially	0
reversible	0
metabolic	0
derangement	0
as	0
the	0
basis	0
for	0
this	0
syndrome	0
.	0

Prenatal	0
exposure	0
to	0
fluoxetine	1
induces	0
fetal	3
pulmonary	4
hypertension	4
in	0
the	0
rat	0
.	0

RATI0NALE	0
:	0
Fluoxetine	1
is	0
a	0
selective	0
serotonin	1
reuptake	0
inhibitor	0
antidepressant	0
widely	0
used	0
by	0
pregnant	0
women	0
.	0

Epidemiological	0
data	0
suggest	0
that	0
fluoxetine	1
exposure	0
prenatally	0
increases	0
the	0
prevalence	0
of	0
persistent	0
pulmonary	3
hypertension	4
syndrome	4
of	0
the	0
newborn	0
.	0

The	0
mechanism	0
responsible	0
for	0
this	0
effect	0
is	0
unclear	0
and	0
paradoxical	0
,	0
considering	0
the	0
current	0
evidence	0
of	0
a	0
pulmonary	3
hypertension	4
protective	0
fluoxetine	1
effect	0
in	0
adult	0
rodents	0
.	0

0BJECTIVES	0
:	0
To	0
evaluate	0
the	0
fluoxetine	1
effect	0
on	0
fetal	0
rat	0
pulmonary	0
vascular	0
smooth	0
muscle	0
mechanical	0
properties	0
and	0
cell	0
proliferation	0
rate	0
.	0

METH0DS	0
:	0
Pregnant	0
rats	0
were	0
treated	0
with	0
fluoxetine	1
(	0
10	0
mg	0
/	0
kg	0
)	0
from	0
Day	0
11	0
through	0
Day	0
21	0
of	0
gestation	0
.	0

MEASUREMENTS	0
AND	0
MAIN	0
RESULTS	0
:	0
Fetuses	0
were	0
delivered	0
by	0
cesarean	0
section	0
.	0

As	0
compared	0
with	0
controls	0
,	0
fluoxetine	1
exposure	0
resulted	0
in	0
fetal	3
pulmonary	4
hypertension	4
as	0
evidenced	0
by	0
an	0
increase	0
in	0
the	0
weight	0
ratio	0
of	0
the	0
right	0
ventricle	0
to	0
the	0
left	0
ventricle	0
plus	0
septum	0
(	0
P	0
=	0
0	0
.	0
02	0
)	0
and	0
by	0
an	0
increase	0
in	0
pulmonary	0
arterial	0
medial	0
thickness	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

Postnatal	0
mortality	0
was	0
increased	0
among	0
experimental	0
animals	0
,	0
and	0
arterial	0
oxygen	1
saturation	0
was	0
96	0
+	0
/	0
-	0
1	0
%	0
in	0
1	0
-	0
day	0
-	0
old	0
control	0
animals	0
and	0
significantly	0
lower	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
in	0
fluoxetine	1
-	0
exposed	0
pups	0
(	0
79	0
+	0
/	0
-	0
2	0
%	0
)	0
.	0

In	0
vitro	0
,	0
fluoxetine	1
induced	0
pulmonary	0
arterial	0
muscle	0
contraction	0
in	0
fetal	0
,	0
but	0
not	0
adult	0
,	0
animals	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
and	0
reduced	0
serotonin	1
-	0
induced	0
contraction	0
at	0
both	0
ages	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

After	0
in	0
utero	0
exposure	0
to	0
a	0
low	0
fluoxetine	1
concentration	0
the	0
pulmonary	0
arterial	0
smooth	0
muscle	0
cell	0
proliferation	0
rate	0
was	0
significantly	0
increased	0
in	0
fetal	0
,	0
but	0
not	0
adult	0
,	0
cells	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

C0NCLUSI0NS	0
:	0
In	0
contrast	0
to	0
the	0
adult	0
,	0
fluoxetine	1
exposure	0
in	0
utero	0
induces	0
pulmonary	3
hypertension	4
in	0
the	0
fetal	0
rat	0
as	0
a	0
result	0
of	0
a	0
developmentally	0
regulated	0
increase	0
in	0
pulmonary	0
vascular	0
smooth	0
muscle	0
proliferation	0
.	0

Disulfiram	1
-	0
induced	0
transient	0
optic	3
and	4
peripheral	4
neuropathy	4
:	0
a	0
case	0
report	0
.	0

AIM	0
:	0
To	0
report	0
a	0
case	0
of	0
optic	3
and	4
peripheral	4
neuropathy	4
after	0
chronic	0
use	0
of	0
disulfiram	1
for	0
alcohol	3
dependence	4
management	0
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
A	0
case	0
report	0
.	0

RESULTS	0
:	0
A	0
57	0
-	0
year	0
-	0
old	0
male	0
presented	0
with	0
gradual	0
loss	3
of	4
vision	4
in	0
both	0
eyes	0
with	0
intermittent	0
headaches	3
for	0
2	0
months	0
.	0

He	0
also	0
complained	0
of	0
paraesthesia	3
with	0
numbness	3
in	0
both	0
feet	0
.	0

His	0
vision	0
was	0
6	0
/	0
15	0
and	0
2	0
/	0
60	0
in	0
the	0
right	0
and	0
left	0
eyes	0
,	0
respectively	0
.	0

Fundoscopy	0
revealed	0
bilaterally	0
swollen	0
optic	0
nerve	0
heads	0
.	0

Visual	0
field	0
testing	0
confirmed	0
bilateral	0
central	0
-	0
caecal	0
scotomata	3
.	0

He	0
had	0
been	0
taking	0
disulfiram	1
for	0
alcohol	3
dependence	4
for	0
the	0
preceding	0
3	0
years	0
.	0

Disulfiram	1
discontinuation	0
lead	0
to	0
an	0
immediate	0
symptomatic	0
improvement	0
.	0

C0NCLUSI0N	0
:	0
Physicians	0
initiating	0
long	0
-	0
term	0
disulfiram	1
therapy	0
should	0
be	0
aware	0
of	0
these	0
adverse	0
effects	0
.	0

They	0
should	0
recommend	0
annual	0
ophthalmic	0
reviews	0
with	0
visual	0
field	0
testing	0
.	0

Patients	0
should	0
be	0
reassured	0
with	0
respect	0
to	0
the	0
reversibility	0
of	0
these	0
adverse	0
effects	0
.	0

Intraocular	0
pressure	0
in	0
patients	0
with	0
uveitis	3
treated	0
with	0
fluocinolone	1
acetonide	2
implants	0
.	0

0BJECTIVE	0
:	0
To	0
report	0
the	0
incidence	0
and	0
management	0
of	0
elevated	3
intraocular	4
pressure	4
(	0
I0P	0
)	0
in	0
patients	0
with	0
uveitis	3
treated	0
with	0
the	0
fluocinolone	1
acetonide	2
(	0
FA	1
)	0
intravitreal	0
implant	0
.	0

DESIGN	0
:	0
Pooled	0
data	0
from	0
3	0
multicenter	0
,	0
double	0
-	0
masked	0
,	0
randomized	0
,	0
controlled	0
,	0
phase	0
2b	0
/	0
3	0
clinical	0
trials	0
evaluating	0
the	0
safety	0
and	0
efficacy	0
of	0
the	0
0	0
.	0
59	0
-	0
mg	0
or	0
2	0
.	0
1	0
-	0
mg	0
FA	1
intravitreal	0
implant	0
or	0
standard	0
therapy	0
were	0
analyzed	0
.	0

RESULTS	0
:	0
During	0
the	0
3	0
-	0
year	0
follow	0
-	0
up	0
,	0
71	0
.	0
0	0
%	0
of	0
implanted	0
eyes	0
had	0
an	0
I0P	0
increase	0
of	0
10	0
mm	0
Hg	0
or	0
more	0
than	0
baseline	0
and	0
55	0
.	0
1	0
%	0
,	0
24	0
.	0
7	0
%	0
,	0
and	0
6	0
.	0
2	0
%	0
of	0
eyes	0
reached	0
an	0
I0P	0
of	0
30	0
mm	0
Hg	0
or	0
more	0
,	0
40	0
mm	0
Hg	0
or	0
more	0
,	0
and	0
50	0
mm	0
Hg	0
or	0
more	0
,	0
respectively	0
.	0

Topical	0
I0P	0
-	0
lowering	0
medication	0
was	0
administered	0
in	0
74	0
.	0
8	0
%	0
of	0
implanted	0
eyes	0
,	0
and	0
I0P	0
-	0
lowering	0
surgeries	0
,	0
most	0
of	0
which	0
were	0
trabeculectomies	0
(	0
76	0
.	0
2	0
%	0
)	0
,	0
were	0
performed	0
on	0
36	0
.	0
6	0
%	0
of	0
implanted	0
eyes	0
.	0

Intraocular	0
pressure	0
-	0
lowering	0
surgeries	0
were	0
considered	0
a	0
success	0
(	0
postoperative	0
I0P	0
of	0
6	0
-	0
21	0
mm	0
Hg	0
with	0
or	0
without	0
additional	0
I0P	0
-	0
lowering	0
medication	0
)	0
in	0
85	0
.	0
1	0
%	0
of	0
eyes	0
at	0
1	0
year	0
.	0

The	0
rate	0
of	0
hypotony	3
(	0
I0P	0
<	0
/	0
=	0
5	0
mm	0
Hg	0
)	0
following	0
I0P	0
-	0
lowering	0
surgery	0
(	0
42	0
.	0
5	0
%	0
)	0
was	0
not	0
different	0
from	0
that	0
of	0
implanted	0
eyes	0
not	0
subjected	0
to	0
surgery	0
(	0
35	0
.	0
4	0
%	0
)	0
(	0
P	0
=	0
.	0
09	0
)	0
.	0

C0NCLUSI0N	0
:	0
Elevated	0
I0P	0
is	0
a	0
significant	0
complication	0
with	0
the	0
FA	0
intravitreal	0
implant	0
but	0
may	0
be	0
controlled	0
with	0
medication	0
and	0
surgery	0
.	0

Myocardial	0
Fas	0
ligand	0
expression	0
increases	0
susceptibility	0
to	0
AZT	1
-	0
induced	0
cardiomyopathy	3
.	0

BACKGR0UND	0
:	0
Dilated	3
cardiomyopathy	4
(	0
DCM	3
)	0
and	0
myocarditis	3
occur	0
in	0
many	0
HIV	3
-	4
infected	4
individuals	0
,	0
resulting	0
in	0
symptomatic	0
heart	3
failure	4
in	0
up	0
to	0
5	0
%	0
of	0
patients	0
.	0

Highly	0
active	0
antiretroviral	0
therapy	0
(	0
HAART	0
)	0
has	0
significantly	0
reduced	0
morbidity	0
and	0
mortality	0
of	0
acquired	3
immunodeficiency	4
syndrome	4
(	0
AIDS	3
)	0
,	0
but	0
has	0
resulted	0
in	0
an	0
increase	0
in	0
cardiac	3
and	4
skeletal	4
myopathies	4
.	0

METH0DS	0
AND	0
RESULTS	0
:	0
In	0
order	0
to	0
investigate	0
whether	0
the	0
HAART	0
component	0
zidovudine	1
(	0
3	1
'	2
-	2
azido	2
-	2
2	2
'	2
,	2
3	2
'	2
-	2
deoxythymidine	2
;	0
AZT	1
)	0
triggers	0
the	0
Fas	0
-	0
dependent	0
cell	0
-	0
death	0
pathway	0
and	0
cause	0
cytoskeletal	0
disruption	0
in	0
a	0
murine	0
model	0
of	0
DCM	3
,	0
8	0
-	0
week	0
-	0
old	0
transgenic	0
(	0
expressing	0
Fas	0
ligand	0
in	0
the	0
myocardium	0
:	0
FasL	0
Tg	0
)	0
and	0
non	0
-	0
transgenic	0
(	0
NTg	0
)	0
mice	0
received	0
water	0
ad	0
libitum	0
containing	0
different	0
concentrations	0
of	0
AZT	1
(	0
0	0
,	0
0	0
.	0
07	0
,	0
0	0
.	0
2	0
,	0
and	0
0	0
.	0
7	0
mg	0
/	0
ml	0
)	0
.	0

After	0
6	0
weeks	0
,	0
cardiac	0
function	0
was	0
assessed	0
by	0
echocardiography	0
and	0
morphology	0
was	0
assessed	0
by	0
histopathologic	0
and	0
immunohistochemical	0
methods	0
.	0

NTg	0
and	0
untreated	0
FasL	0
Tg	0
mice	0
showed	0
little	0
or	0
no	0
change	0
in	0
cardiac	0
structure	0
or	0
function	0
.	0

In	0
contrast	0
,	0
AZT	1
-	0
treated	0
FasL	0
Tg	0
mice	0
developed	0
cardiac	3
dilation	4
and	0
depressed	0
cardiac	0
function	0
in	0
a	0
dose	0
-	0
dependent	0
manner	0
,	0
with	0
concomitant	0
inflammatory	0
infiltration	0
of	0
both	0
ventricles	0
.	0

These	0
changes	0
were	0
associated	0
with	0
an	0
increased	0
sarcolemmal	0
expression	0
of	0
Fas	0
and	0
FasL	0
,	0
as	0
well	0
as	0
increased	0
activation	0
of	0
caspase	0
3	0
,	0
translocation	0
of	0
calpain	0
1	0
to	0
the	0
sarcolemma	0
and	0
sarcomere	0
,	0
and	0
increased	0
numbers	0
of	0
cells	0
undergoing	0
apoptosis	0
.	0

These	0
were	0
associated	0
with	0
changes	0
in	0
dystrophin	0
and	0
cardiac	0
troponin	0
I	0
localization	0
,	0
as	0
well	0
as	0
loss	0
of	0
sarcolemmal	0
integrity	0
.	0

C0NCLUSI0NS	0
:	0
The	0
expression	0
of	0
Fas	0
ligand	0
in	0
the	0
myocardium	0
,	0
as	0
identified	0
in	0
HIV	0
-	0
positive	0
patients	0
,	0
might	0
increase	0
the	0
susceptibility	0
to	0
HAART	0
-	0
induced	0
cardiomyopathy	3
due	0
to	0
activation	0
of	0
apoptotic	0
pathways	0
,	0
resulting	0
in	0
cardiac	3
dilation	4
and	4
dysfunction	4
.	0

Gastrointestinal	0
tolerability	0
of	0
etoricoxib	1
in	0
rheumatoid	3
arthritis	4
patients	0
:	0
results	0
of	0
the	0
etoricoxib	1
vs	0
diclofenac	1
sodium	2
gastrointestinal	0
tolerability	0
and	0
effectiveness	0
trial	0
(	0
EDGE	0
-	0
II	0
)	0
.	0

0BJECTIVE	0
:	0
A	0
randomised	0
,	0
double	0
-	0
blind	0
study	0
to	0
compare	0
the	0
gastrointestinal	0
(	0
GI	0
)	0
tolerability	0
,	0
safety	0
and	0
efficacy	0
of	0
etoricoxib	1
and	0
diclofenac	1
in	0
patients	0
with	0
rheumatoid	3
arthritis	4
(	0
RA	3
)	0
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
A	0
total	0
of	0
4086	0
patients	0
(	0
mean	0
age	0
60	0
.	0
8	0
years	0
)	0
diagnosed	0
with	0
RA	3
were	0
enrolled	0
and	0
received	0
etoricoxib	1
90	0
mg	0
daily	0
(	0
n	0
=	0
2032	0
)	0
or	0
diclofenac	1
75	0
mg	0
twice	0
daily	0
(	0
n	0
=	0
2054	0
)	0
.	0

Use	0
of	0
gastroprotective	0
agents	0
and	0
low	0
-	0
dose	0
aspirin	1
was	0
allowed	0
.	0

The	0
prespecified	0
primary	0
end	0
point	0
consisted	0
of	0
the	0
cumulative	0
rate	0
of	0
patient	0
discontinuations	0
due	0
to	0
clinical	0
and	0
laboratory	0
GI	0
adverse	0
experiences	0
(	0
AEs	0
)	0
.	0

General	0
safety	0
was	0
also	0
assessed	0
,	0
including	0
adjudicated	0
thrombotic	3
cardiovascular	4
event	0
data	0
.	0

Efficacy	0
was	0
evaluated	0
using	0
the	0
Patient	0
Global	0
Assessment	0
of	0
Disease	0
Status	0
(	0
PGADS	0
;	0
0	0
-	0
4	0
point	0
scale	0
)	0
.	0

RESULTS	0
:	0
Mean	0
(	0
SD	0
;	0
maximum	0
)	0
duration	0
of	0
treatment	0
was	0
19	0
.	0
3	0
(	0
10	0
.	0
3	0
;	0
32	0
.	0
9	0
)	0
and	0
19	0
.	0
1	0
(	0
10	0
.	0
4	0
;	0
33	0
.	0
1	0
)	0
months	0
in	0
the	0
etoricoxib	1
and	0
diclofenac	1
groups	0
,	0
respectively	0
.	0

The	0
cumulative	0
discontinuation	0
rate	0
due	0
to	0
GI	3
AEs	4
was	0
significantly	0
lower	0
with	0
etoricoxib	1
than	0
diclofenac	1
(	0
5	0
.	0
2	0
vs	0
8	0
.	0
5	0
events	0
per	0
100	0
patient	0
-	0
years	0
,	0
respectively	0
;	0
hazard	0
ratio	0
0	0
.	0
62	0
(	0
95	0
%	0
CI	0
:	0
0	0
.	0
47	0
,	0
0	0
.	0
81	0
;	0
p	0
<	0
or	0
=	0
0	0
.	0
001	0
)	0
)	0
.	0

The	0
incidence	0
of	0
discontinuations	0
for	0
hypertension	3
-	0
related	0
and	0
oedema	3
-	0
related	0
AEs	0
were	0
significantly	0
higher	0
with	0
etoricoxib	1
(	0
2	0
.	0
5	0
%	0
and	0
1	0
.	0
1	0
%	0
respectively	0
)	0
compared	0
with	0
diclofenac	1
(	0
1	0
.	0
5	0
%	0
and	0
0	0
.	0
4	0
%	0
respectively	0
;	0
p	0
<	0
0	0
.	0
001	0
for	0
hypertension	3
and	0
p	0
<	0
0	0
.	0
01	0
for	0
oedema	3
)	0
.	0

Etoricoxib	1
and	0
diclofenac	1
treatment	0
resulted	0
in	0
similar	0
efficacy	0
(	0
PGADS	0
mean	0
changes	0
from	0
baseline	0
-	0
0	0
.	0
62	0
vs	0
-	0
0	0
.	0
58	0
,	0
respectively	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Etoricoxib	1
90	0
mg	0
demonstrated	0
a	0
significantly	0
lower	0
risk	0
for	0
discontinuing	0
treatment	0
due	0
to	0
GI	3
AEs	4
compared	0
with	0
diclofenac	1
150	0
mg	0
.	0

Discontinuations	0
from	0
renovascular	0
AEs	0
,	0
although	0
less	0
common	0
than	0
discontinuations	0
from	0
GI	3
AEs	4
,	0
were	0
significantly	0
higher	0
with	0
etoricoxib	1
.	0

Anxiogenic	0
potential	0
of	0
ciprofloxacin	1
and	0
norfloxacin	1
in	0
rats	0
.	0

INTR0DUCTI0N	0
:	0
The	0
possible	0
anxiogenic	0
effects	0
of	0
fluoroquinolones	1
,	0
namely	0
ciprofloxacin	1
and	0
norfloxacin	1
,	0
were	0
investigated	0
in	0
adult	0
Charles	0
Foster	0
albino	0
rats	0
of	0
either	0
sex	0
,	0
weighing	0
150	0
-	0
200	0
g	0
.	0

METH0DS	0
:	0
The	0
drugs	0
were	0
given	0
orally	0
,	0
in	0
doses	0
of	0
50	0
mg	0
/	0
kg	0
for	0
five	0
consecutive	0
days	0
and	0
the	0
experiments	0
were	0
performed	0
on	0
the	0
fifth	0
day	0
.	0

The	0
tests	0
included	0
open	0
-	0
field	0
exploratory	0
behaviour	0
,	0
elevated	0
plus	0
maze	0
and	0
elevated	0
zero	0
maze	0
,	0
social	0
interaction	0
and	0
novelty	0
-	0
suppressed	0
feeding	0
latency	0
behaviour	0
.	0

RESULTS	0
:	0
The	0
results	0
indicate	0
that	0
ciprofloxacin	1
-	0
and	0
norfloxacin	1
-	0
treated	0
rats	0
showed	0
anxious	3
behaviour	4
in	0
comparison	0
to	0
control	0
rats	0
in	0
all	0
the	0
parameters	0
studied	0
.	0

However	0
,	0
ciprofloxacin	1
-	0
and	0
norfloxacin	1
-	0
treated	0
rats	0
did	0
not	0
differ	0
significantly	0
from	0
each	0
other	0
in	0
various	0
behavioural	0
parameters	0
.	0

C0NCLUSI0N	0
:	0
The	0
present	0
experimental	0
findings	0
substantiate	0
the	0
clinically	0
observed	0
anxiogenic	0
potential	0
of	0
ciprofloxacin	1
and	0
norfloxacin	1
.	0

Reduction	0
of	0
pain	3
during	0
induction	0
with	0
target	0
-	0
controlled	0
propofol	1
and	0
remifentanil	1
.	0

BACKGR0UND	0
:	0
Pain	3
on	0
injection	0
of	0
propofol	1
is	0
unpleasant	0
.	0

We	0
hypothesized	0
that	0
propofol	1
infusion	0
pain	3
might	0
be	0
prevented	0
by	0
infusing	0
remifentanil	1
before	0
starting	0
the	0
propofol	1
infusion	0
in	0
a	0
clinical	0
setting	0
where	0
target	0
-	0
controlled	0
infusions	0
(	0
TCI	0
)	0
of	0
both	0
drugs	0
were	0
used	0
.	0

A	0
prospective	0
,	0
randomized	0
,	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
trial	0
was	0
performed	0
to	0
determine	0
the	0
effect	0
-	0
site	0
concentration	0
(	0
Ce	0
)	0
of	0
remifentanil	1
to	0
prevent	0
the	0
pain	3
without	0
producing	0
complications	0
.	0

METH0DS	0
:	0
A	0
total	0
of	0
128	0
patients	0
undergoing	0
general	0
surgery	0
were	0
randomly	0
allocated	0
to	0
receive	0
normal	0
saline	0
(	0
control	0
)	0
or	0
remifentanil	1
to	0
a	0
target	0
Ce	0
of	0
2	0
ng	0
ml	0
(	0
-	0
1	0
)	0
(	0
R2	0
)	0
,	0
4	0
ng	0
ml	0
(	0
-	0
1	0
)	0
(	0
R4	0
)	0
,	0
or	0
6	0
ng	0
ml	0
(	0
-	0
1	0
)	0
(	0
R6	0
)	0
administered	0
via	0
TCI	0
.	0

After	0
the	0
target	0
Ce	0
was	0
achieved	0
,	0
the	0
infusion	0
of	0
propofol	1
was	0
started	0
.	0

Remifentanil	1
-	0
related	0
complications	0
were	0
assessed	0
during	0
the	0
remifentanil	1
infusion	0
,	0
and	0
pain	3
caused	0
by	0
propofol	1
was	0
evaluated	0
using	0
a	0
four	0
-	0
point	0
scale	0
during	0
the	0
propofol	1
infusion	0
.	0

RESULTS	0
:	0
The	0
incidence	0
of	0
pain	3
was	0
significantly	0
lower	0
in	0
Groups	0
R4	0
and	0
R6	0
than	0
in	0
the	0
control	0
and	0
R2	0
groups	0
(	0
12	0
/	0
32	0
and	0
6	0
/	0
31	0
vs	0
26	0
/	0
31	0
and	0
25	0
/	0
32	0
,	0
respectively	0
,	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

Pain	3
was	0
less	0
severe	0
in	0
Groups	0
R4	0
and	0
R6	0
than	0
in	0
the	0
control	0
and	0
R2	0
groups	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

However	0
,	0
both	0
incidence	0
and	0
severity	0
of	0
pain	3
were	0
not	0
different	0
between	0
Groups	0
R4	0
and	0
R6	0
.	0

No	0
significant	0
complications	0
were	0
observed	0
during	0
the	0
study	0
.	0

C0NCLUSI0NS	0
:	0
During	0
induction	0
of	0
anaesthesia	0
with	0
TCI	0
of	0
propofol	1
and	0
remifentanil	1
,	0
a	0
significant	0
reduction	0
in	0
propofol	1
infusion	0
pain	3
was	0
achieved	0
without	0
significant	0
complications	0
by	0
prior	0
administration	0
of	0
remifentanil	1
at	0
a	0
target	0
Ce	0
of	0
4	0
ng	0
ml	0
(	0
-	0
1	0
)	0
.	0

Dexmedetomidine	1
and	0
cardiac	0
protection	0
for	0
non	0
-	0
cardiac	0
surgery	0
:	0
a	0
meta	0
-	0
analysis	0
of	0
randomised	0
controlled	0
trials	0
.	0

We	0
conducted	0
a	0
systematic	0
review	0
of	0
the	0
effects	0
of	0
dexmedetomidine	1
on	0
cardiac	0
outcomes	0
following	0
non	0
-	0
cardiac	0
surgery	0
.	0

We	0
included	0
prospective	0
,	0
randomised	0
peri	0
-	0
operative	0
studies	0
of	0
dexmedetomidine	1
that	0
reported	0
mortality	0
,	0
cardiac	0
morbidity	0
or	0
adverse	0
drug	0
events	0
.	0

A	0
PubMed	0
Central	0
and	0
EMBASE	0
search	0
was	0
conducted	0
up	0
to	0
July	0
2007	0
.	0

The	0
reference	0
lists	0
of	0
identified	0
papers	0
were	0
examined	0
for	0
further	0
trials	0
.	0

0f	0
425	0
studies	0
identified	0
,	0
20	0
were	0
included	0
in	0
the	0
meta	0
-	0
analysis	0
(	0
840	0
patients	0
)	0
.	0

Dexmedetomidine	1
was	0
associated	0
with	0
a	0
trend	0
towards	0
improved	0
cardiac	0
outcomes	0
;	0
all	0
-	0
cause	0
mortality	0
(	0
0R	0
0	0
.	0
27	0
,	0
95	0
%	0
CI	0
0	0
.	0
01	0
-	0
7	0
.	0
13	0
,	0
p	0
=	0
0	0
.	0
44	0
)	0
,	0
non	0
-	0
fatal	0
myocardial	3
infarction	4
(	0
0R	0
0	0
.	0
26	0
,	0
95	0
%	0
CI	0
0	0
.	0
04	0
-	0
1	0
.	0
60	0
,	0
p	0
=	0
0	0
.	0
14	0
)	0
,	0
and	0
myocardial	3
ischaemia	4
(	0
0R	0
0	0
.	0
65	0
,	0
95	0
%	0
CI	0
0	0
.	0
26	0
-	0
1	0
.	0
63	0
,	0
p	0
=	0
0	0
.	0
36	0
)	0
.	0

Peri	0
-	0
operative	0
hypotension	3
(	0
26	0
%	0
,	0
0R	0
3	0
.	0
80	0
,	0
95	0
%	0
CI	0
1	0
.	0
91	0
-	0
7	0
.	0
54	0
,	0
p	0
=	0
0	0
.	0
0001	0
)	0
and	0
bradycardia	3
(	0
17	0
%	0
,	0
0R	0
5	0
.	0
45	0
,	0
95	0
%	0
CI	0
2	0
.	0
98	0
-	0
9	0
.	0
95	0
,	0
p	0
<	0
0	0
.	0
00001	0
)	0
were	0
significantly	0
increased	0
.	0

An	0
anticholinergic	0
did	0
not	0
reduce	0
the	0
incidence	0
of	0
bradycardia	3
(	0
p	0
=	0
0	0
.	0
43	0
)	0
.	0

A	0
randomised	0
placebo	0
-	0
controlled	0
trial	0
of	0
dexmedetomidine	1
is	0
warranted	0
.	0

Myocardial	3
infarction	4
in	0
pregnancy	0
associated	0
with	0
clomiphene	1
citrate	2
for	0
ovulation	0
induction	0
:	0
a	0
case	0
report	0
.	0

BACKGR0UND	0
:	0
Clomiphene	1
citrate	2
(	0
CC	1
)	0
is	0
commonly	0
prescribed	0
for	0
ovulation	0
induction	0
.	0

It	0
is	0
considered	0
safe	0
,	0
with	0
minimal	0
side	0
effects	0
.	0

Thromboembolism	3
is	0
a	0
rare	0
but	0
life	0
-	0
threatening	0
complication	0
that	0
has	0
been	0
reported	0
after	0
ovulation	0
induction	0
with	0
CC	1
.	0

Spontaneous	0
coronary	3
thrombosis	4
or	0
thromboembolism	3
with	0
subsequent	0
clot	0
lysis	0
has	0
been	0
suggested	0
as	0
one	0
of	0
the	0
most	0
common	0
causes	0
of	0
myocardial	3
infarction	4
(	0
MI	3
)	0
during	0
pregnancy	0
,	0
with	0
a	0
subsequently	0
normal	0
coronary	0
angiogram	0
.	0

CASE	0
:	0
A	0
33	0
-	0
year	0
-	0
old	0
woman	0
with	0
a	0
5	0
-	0
week	0
gestation	0
had	0
recently	0
received	0
CC	1
for	0
ovulation	0
induction	0
and	0
presented	0
with	0
chest	3
pain	4
.	0

An	0
electrocardiogram	0
showed	0
a	0
lateral	0
and	0
anterior	0
wall	0
myocardial	3
infarction	4
.	0

Cardiac	0
enzymes	0
showed	0
a	0
peak	0
rise	0
in	0
troponin	0
I	0
to	0
9	0
.	0
10	0
ng	0
/	0
mL	0
.	0

An	0
initial	0
exercise	0
stress	0
test	0
was	0
normal	0
.	0

At	0
the	0
time	0
of	0
admission	0
,	0
the	0
patient	0
was	0
at	0
high	0
risk	0
of	0
radiation	3
injury	4
to	0
the	0
fetus	0
,	0
so	0
a	0
coronary	0
angiogram	0
was	0
postponed	0
until	0
the	0
second	0
trimester	0
.	0

It	0
showed	0
normal	0
coronary	0
vessels	0
.	0

C0NCLUSI0N	0
:	0
This	0
appears	0
to	0
be	0
the	0
first	0
reported	0
case	0
documenting	0
a	0
possible	0
association	0
between	0
CC	1
and	0
myocardial	3
infarction	4
.	0

Thrombosis	3
might	0
be	0
a	0
rare	0
but	0
hazardous	0
complication	0
of	0
CC	1
.	0

Given	0
this	0
life	0
-	0
threatening	0
complication	0
,	0
appropriate	0
prophylactic	0
measures	0
should	0
be	0
used	0
in	0
high	0
-	0
risk	0
woman	0
undergoing	0
ovarian	0
stimulation	0
.	0

Reverse	0
or	0
inverted	0
left	3
ventricular	4
apical	4
ballooning	4
syndrome	4
(	0
reverse	0
Takotsubo	3
cardiomyopathy	4
)	0
in	0
a	0
young	0
woman	0
in	0
the	0
setting	0
of	0
amphetamine	1
use	0
.	0

Transient	0
left	3
ventricular	4
apical	4
ballooning	4
syndrome	4
was	0
first	0
described	0
in	0
Japan	0
as	0
"	0
Takotsubo	3
cardiomyopathy	4
.	0
"	0
This	0
syndrome	0
has	0
been	0
identified	0
in	0
many	0
other	0
countries	0
.	0

Many	0
variations	0
of	0
this	0
syndrome	0
have	0
been	0
recently	0
described	0
in	0
the	0
literature	0
.	0

0ne	0
of	0
the	0
rarest	0
is	0
the	0
reverse	0
type	0
of	0
this	0
syndrome	0
,	0
with	0
hyperdynamic	0
apex	0
and	0
complete	0
akinesia	3
of	0
the	0
base	0
(	0
as	0
opposed	0
to	0
the	0
classic	0
apical	3
ballooning	4
)	0
.	0

In	0
this	0
article	0
,	0
we	0
report	0
an	0
interesting	0
case	0
of	0
a	0
young	0
woman	0
who	0
presented	0
with	0
this	0
rare	0
type	0
of	0
reverse	0
apical	3
ballooning	4
syndrome	4
occurring	0
after	0
amphetamine	1
use	0
.	0

This	0
report	0
is	0
followed	0
by	0
review	0
of	0
the	0
literature	0
.	0

Results	0
of	0
a	0
comparative	0
,	0
phase	0
III	0
,	0
12	0
-	0
week	0
,	0
multicenter	0
,	0
prospective	0
,	0
randomized	0
,	0
double	0
-	0
blind	0
assessment	0
of	0
the	0
efficacy	0
and	0
tolerability	0
of	0
a	0
fixed	0
-	0
dose	0
combination	0
of	0
telmisartan	1
and	0
amlodipine	1
versus	0
amlodipine	1
monotherapy	0
in	0
Indian	0
adults	0
with	0
stage	0
II	0
hypertension	3
.	0

0BJECTIVE	0
:	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
evaluate	0
the	0
efficacy	0
and	0
tolerability	0
of	0
a	0
new	0
fixed	0
-	0
dose	0
combination	0
(	0
FDC	0
)	0
of	0
telmisartan	1
40	0
mg	0
+	0
amlodipine	1
5	0
mg	0
(	0
T	0
+	0
A	0
)	0
compared	0
with	0
amlodipine	1
5	0
-	0
mg	0
monotherapy	0
(	0
A	0
)	0
in	0
adult	0
Indian	0
patients	0
with	0
stage	0
II	0
hypertension	3
.	0

METH0DS	0
:	0
This	0
comparative	0
,	0
Phase	0
III	0
,	0
12	0
-	0
week	0
,	0
multicenter	0
,	0
prospective	0
,	0
randomized	0
,	0
double	0
-	0
blind	0
study	0
was	0
conducted	0
in	0
Indian	0
patients	0
aged	0
18	0
to	0
65	0
years	0
with	0
established	0
stage	0
II	0
hypertension	3
.	0

Patients	0
were	0
treated	0
with	0
oral	0
FDC	0
of	0
T	0
+	0
A	0
or	0
A	0
QD	0
before	0
breakfast	0
for	0
12	0
weeks	0
;	0
blood	0
pressure	0
(	0
BP	0
)	0
and	0
heart	0
rate	0
were	0
measured	0
in	0
the	0
sitting	0
position	0
.	0

Primary	0
efficacy	0
end	0
points	0
were	0
reduction	0
in	0
clinical	0
systolic	0
BP	0
(	0
SBP	0
)	0
/	0
diastolic	0
BP	0
(	0
DBP	0
)	0
from	0
baseline	0
to	0
study	0
end	0
and	0
number	0
of	0
responders	0
(	0
ie	0
,	0
patients	0
who	0
achieved	0
target	0
SBP	0
/	0
DBP	0
<	0
130	0
/	0
<	0
80	0
mm	0
Hg	0
)	0
at	0
end	0
of	0
study	0
.	0

Tolerability	0
was	0
assessed	0
by	0
treatment	0
-	0
emergent	0
adverse	0
events	0
,	0
identified	0
using	0
physical	0
examination	0
,	0
laboratory	0
analysis	0
,	0
and	0
electrocardiography	0
.	0

RESULTS	0
:	0
A	0
total	0
of	0
210	0
patients	0
were	0
enrolled	0
in	0
the	0
study	0
;	0
203	0
patients	0
(	0
143	0
men	0
,	0
60	0
women	0
)	0
completed	0
the	0
study	0
while	0
7	0
were	0
lost	0
to	0
follow	0
-	0
up	0
(	0
4	0
patients	0
in	0
the	0
T	0
+	0
A	0
group	0
and	0
3	0
in	0
the	0
A	0
group	0
)	0
and	0
considered	0
with	0
-	0
drawn	0
.	0

At	0
study	0
end	0
,	0
statistically	0
significant	0
percentage	0
reductions	0
from	0
baseline	0
within	0
groups	0
and	0
between	0
groups	0
were	0
observed	0
in	0
SBP	0
(	0
T	0
+	0
A	0
[	0
-	0
27	0
.	0
4	0
%	0
]	0
;	0
A	0
[	0
-	0
16	0
.	0
6	0
%	0
]	0
)	0
and	0
DBP	0
(	0
T	0
+	0
A	0
[	0
-	0
20	0
.	0
1	0
%	0
]	0
;	0
A	0
[	0
-	0
13	0
.	0
3	0
%	0
]	0
)	0
(	0
all	0
,	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

Response	0
rates	0
were	0
87	0
.	0
3	0
%	0
(	0
89	0
/	0
102	0
)	0
in	0
the	0
T	0
+	0
A	0
group	0
and	0
69	0
.	0
3	0
%	0
(	0
70	0
/	0
101	0
)	0
in	0
the	0
A	0
group	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

The	0
prevalences	0
of	0
adverse	0
events	0
were	0
not	0
significantly	0
different	0
between	0
the	0
2	0
treatment	0
groups	0
(	0
T	0
+	0
A	0
,	0
16	0
.	0
0	0
%	0
[	0
17	0
/	0
106	0
]	0
;	0
A	0
,	0
15	0
.	0
4	0
%	0
[	0
16	0
/	0
104	0
]	0
)	0
.	0

Peripheral	0
edema	3
was	0
reported	0
in	0
8	0
.	0
5	0
%	0
patients	0
(	0
9	0
/	0
106	0
)	0
in	0
the	0
T	0
+	0
A	0
group	0
compared	0
with	0
13	0
.	0
5	0
%	0
(	0
14	0
/	0
104	0
)	0
in	0
the	0
A	0
group	0
,	0
and	0
cough	3
was	0
reported	0
in	0
3	0
.	0
8	0
%	0
patients	0
(	0
4	0
/	0
106	0
)	0
in	0
the	0
T	0
+	0
A	0
group	0
and	0
1	0
.	0
0	0
%	0
(	0
1	0
/	0
104	0
)	0
patients	0
in	0
the	0
A	0
group	0
;	0
these	0
differences	0
did	0
not	0
reach	0
statistical	0
significance	0
.	0

The	0
incidences	0
of	0
headache	3
,	0
dizziness	3
,	0
and	0
diarrhea	3
were	0
similar	0
between	0
the	0
2	0
groups	0
.	0

C0NCLUSI0NS	0
:	0
Among	0
these	0
Indian	0
patients	0
with	0
stage	0
II	0
hypertension	3
,	0
the	0
FDC	0
of	0
T	0
+	0
A	0
was	0
found	0
to	0
be	0
significantly	0
more	0
effective	0
,	0
with	0
regard	0
to	0
BP	0
reductions	0
,	0
than	0
A	0
,	0
and	0
both	0
treatments	0
were	0
well	0
tolerated	0
.	0

Increased	0
mental	3
slowing	4
associated	0
with	0
the	0
AP0E	0
epsilon4	0
allele	0
after	0
trihexyphenidyl	1
oral	0
anticholinergic	0
challenge	0
in	0
healthy	0
elderly	0
.	0

0BJECTIVES	0
:	0
The	0
objectives	0
of	0
this	0
study	0
were	0
to	0
examine	0
the	0
relationship	0
between	0
AP0E	0
epsilon4	0
and	0
subjective	0
effects	0
of	0
trihexyphenidyl	1
on	0
measures	0
reflecting	0
sedation	0
and	0
confusion	3
and	0
to	0
investigate	0
the	0
relationship	0
between	0
trihexyphenidyl	1
-	0
induced	0
subjective	0
effects	0
and	0
objective	0
memory	0
performance	0
.	0

METH0DS	0
:	0
This	0
study	0
comprised	0
24	0
cognitively	0
intact	0
,	0
health	0
elderly	0
adults	0
(	0
12	0
AP0E	0
epsilon4	0
carriers	0
)	0
at	0
an	0
outpatient	0
geriatric	0
psychiatry	0
research	0
clinic	0
.	0

This	0
was	0
a	0
randomized	0
,	0
double	0
blind	0
,	0
placebo	0
-	0
controlled	0
,	0
three	0
-	0
way	0
,	0
crossover	0
experimental	0
design	0
.	0

All	0
participants	0
received	0
1	0
.	0
0	0
mg	0
or	0
2	0
.	0
0	0
mg	0
trihexyphenidyl	1
or	0
placebo	0
administered	0
in	0
counterbalanced	0
sequences	0
over	0
a	0
period	0
of	0
three	0
consecutive	0
weeks	0
.	0

Bond	0
and	0
Lader	0
'	0
s	0
visual	0
analog	0
scales	0
and	0
alternate	0
versions	0
of	0
the	0
Buschke	0
Selective	0
Reminding	0
Test	0
were	0
administered	0
in	0
a	0
repeated	0
measures	0
design	0
at	0
baseline	0
,	0
1	0
,	0
2	0
.	0
5	0
,	0
and	0
5	0
hours	0
postdrug	0
administration	0
.	0

RESULTS	0
:	0
A	0
2	0
.	0
0	0
-	0
mg	0
oral	0
dose	0
of	0
trihexyphenidyl	1
resulted	0
in	0
increased	0
subjective	0
ratings	0
of	0
mental	3
slowness	4
in	0
carriers	0
of	0
the	0
AP0E	0
epsilon4	0
allele	0
only	0
.	0

Drug	0
effects	0
as	0
determined	0
by	0
difference	0
scores	0
between	0
2	0
.	0
0	0
mg	0
trihexyphenidyl	1
and	0
placebo	0
on	0
ratings	0
of	0
mental	3
slowness	4
significantly	0
correlated	0
with	0
total	0
and	0
delayed	0
recall	0
on	0
the	0
Buschke	0
Selective	0
Reminding	0
Test	0
in	0
carriers	0
of	0
the	0
AP0E	0
epsilon4	0
allele	0
only	0
.	0

However	0
,	0
no	0
significant	0
effects	0
were	0
found	0
with	0
other	0
visual	0
analog	0
scales	0
reflecting	0
subjective	0
sedation	0
and	0
clear	0
-	0
headedness	0
.	0

C0NCLUSI0N	0
:	0
The	0
epsilon4	0
allele	0
in	0
healthy	0
elderly	0
was	0
associated	0
with	0
increased	0
subjective	0
mental	3
slowing	4
after	0
trihexyphenidyl	1
anticholinergic	0
challenge	0
.	0

An	0
evaluation	0
of	0
amikacin	1
nephrotoxicity	3
in	0
the	0
hematology	0
/	0
oncology	0
population	0
.	0

Amikacin	1
is	0
an	0
aminoglycoside	1
commonly	0
used	0
to	0
provide	0
empirical	0
double	0
gram	0
-	0
negative	0
treatment	0
for	0
febrile	3
neutropenia	4
and	0
other	0
suspected	0
infections	3
.	0

Strategies	0
of	0
extended	0
-	0
interval	0
and	0
conventional	0
dosing	0
have	0
been	0
utilized	0
extensively	0
in	0
the	0
general	0
medical	0
population	0
;	0
however	0
,	0
data	0
are	0
lacking	0
to	0
support	0
a	0
dosing	0
strategy	0
in	0
the	0
hematology	0
/	0
oncology	0
population	0
.	0

To	0
evaluate	0
amikacin	1
-	0
associated	0
nephrotoxicity	3
in	0
an	0
adult	0
hematology	0
/	0
oncology	0
population	0
,	0
a	0
prospective	0
,	0
randomized	0
,	0
open	0
-	0
label	0
trial	0
was	0
conducted	0
at	0
a	0
university	0
-	0
affiliated	0
medical	0
center	0
.	0

Forty	0
patients	0
with	0
a	0
diagnosis	0
consistent	0
with	0
a	0
hematologic	3
/	4
oncologic	4
disorder	4
that	0
required	0
treatment	0
with	0
an	0
aminoglycoside	1
were	0
randomized	0
to	0
either	0
conventional	0
or	0
extended	0
-	0
interval	0
amikacin	1
.	0

The	0
occurrence	0
of	0
nephrotoxicity	3
by	0
means	0
of	0
an	0
increase	0
in	0
serum	0
creatinine	1
and	0
evaluation	0
of	0
efficacy	0
via	0
amikacin	1
serum	0
concentrations	0
with	0
respective	0
pathogens	0
were	0
assessed	0
.	0

The	0
occurrence	0
of	0
nephrotoxicity	3
was	0
similar	0
between	0
the	0
conventional	0
and	0
extended	0
-	0
interval	0
groups	0
,	0
at	0
10	0
%	0
and	0
5	0
%	0
,	0
respectively	0
(	0
P	0
=	0
1	0
.	0
00	0
)	0
.	0

Six	0
patients	0
in	0
the	0
conventional	0
group	0
had	0
a	0
positive	0
culture	0
,	0
compared	0
with	0
none	0
in	0
the	0
extended	0
-	0
interval	0
group	0
(	0
P	0
=	0
0	0
.	0
002	0
)	0
.	0

The	0
occurrence	0
of	0
nephrotoxicity	3
was	0
similar	0
between	0
the	0
two	0
dosing	0
regimens	0
,	0
but	0
the	0
distribution	0
of	0
risk	0
factors	0
was	0
variable	0
between	0
the	0
two	0
groups	0
.	0

Efficacy	0
could	0
not	0
be	0
assessed	0
.	0

High	0
dose	0
dexmedetomidine	1
as	0
the	0
sole	0
sedative	0
for	0
pediatric	0
MRI	0
.	0

0BJECTIVE	0
:	0
This	0
large	0
-	0
scale	0
retrospective	0
review	0
evaluates	0
the	0
sedation	0
profile	0
of	0
dexmedetomidine	1
.	0

AIM	0
:	0
To	0
determine	0
the	0
hemodynamic	0
responses	0
,	0
efficacy	0
and	0
adverse	0
events	0
associated	0
with	0
the	0
use	0
of	0
high	0
dose	0
dexmedetomidine	1
as	0
the	0
sole	0
sedative	0
for	0
magnetic	0
resonance	0
imaging	0
(	0
MRI	0
)	0
studies	0
.	0

BACKGR0UND	0
:	0
Dexmedetomidine	1
has	0
been	0
used	0
at	0
our	0
institution	0
since	0
2005	0
to	0
provide	0
sedation	0
for	0
pediatric	0
radiological	0
imaging	0
studies	0
.	0

0ver	0
time	0
,	0
an	0
effective	0
protocol	0
utilizing	0
high	0
dose	0
dexmedetomidine	1
as	0
the	0
sole	0
sedative	0
agent	0
has	0
evolved	0
.	0

METH0DS	0
/	0
MATERIALS	0
:	0
As	0
part	0
of	0
the	0
ongoing	0
Quality	0
Assurance	0
process	0
,	0
data	0
on	0
all	0
sedations	0
are	0
reviewed	0
monthly	0
and	0
protocols	0
modified	0
as	0
needed	0
.	0

Data	0
were	0
analyzed	0
from	0
all	0
747	0
consecutive	0
patients	0
who	0
received	0
dexmedetomidine	1
for	0
MRI	0
sedation	0
from	0
April	0
2005	0
to	0
April	0
2007	0
.	0

RESULTS	0
:	0
Since	0
2005	0
,	0
the	0
10	0
-	0
min	0
loading	0
dose	0
of	0
our	0
dexmedetomidine	1
protocol	0
increased	0
from	0
2	0
to	0
3	0
microg	0
.	0
kg	0
(	0
-	0
1	0
)	0
,	0
and	0
the	0
infusion	0
rate	0
increased	0
from	0
1	0
to	0
1	0
.	0
5	0
to	0
2	0
microg	0
.	0
kg	0
(	0
-	0
1	0
)	0
.	0
h	0
(	0
-	0
1	0
)	0
.	0

The	0
current	0
sedation	0
protocol	0
progressively	0
increased	0
the	0
rate	0
of	0
successful	0
sedation	0
(	0
able	0
to	0
complete	0
the	0
imaging	0
study	0
)	0
when	0
using	0
dexmedetomidine	1
alone	0
from	0
91	0
.	0
8	0
%	0
to	0
97	0
.	0
6	0
%	0
(	0
P	0
=	0
0	0
.	0
009	0
)	0
,	0
reducing	0
the	0
requirement	0
for	0
adjuvant	0
pentobarbital	1
in	0
the	0
event	0
of	0
sedation	0
failure	0
with	0
dexmedetomidine	1
alone	0
and	0
decreased	0
the	0
mean	0
recovery	0
time	0
by	0
10	0
min	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

Although	0
dexmedetomidine	1
sedation	0
was	0
associated	0
with	0
a	0
16	0
%	0
incidence	0
of	0
bradycardia	3
,	0
all	0
concomitant	0
mean	0
arterial	0
blood	0
pressures	0
were	0
within	0
20	0
%	0
of	0
age	0
-	0
adjusted	0
normal	0
range	0
and	0
oxygen	1
saturations	0
were	0
95	0
%	0
or	0
higher	0
.	0

C0NCLUSI0N	0
:	0
Dexmedetomidine	1
in	0
high	0
doses	0
provides	0
adequate	0
sedation	0
for	0
pediatric	0
MRI	0
studies	0
.	0

While	0
use	0
of	0
high	0
dose	0
dexmedetomidine	1
is	0
associated	0
with	0
decreases	0
in	0
heart	0
rate	0
and	0
blood	0
pressure	0
outside	0
the	0
established	0
'	0
awake	0
'	0
norms	0
,	0
this	0
deviation	0
is	0
generally	0
within	0
20	0
%	0
of	0
norms	0
,	0
and	0
is	0
not	0
associated	0
with	0
adverse	0
sequelae	0
.	0

Dexmedetomidine	1
is	0
useful	0
as	0
the	0
sole	0
sedative	0
for	0
pediatric	0
MRI	0
.	0

Hepatotoxicity	3
associated	0
with	0
sulfasalazine	1
in	0
inflammatory	0
arthritis	3
:	0
A	0
case	0
series	0
from	0
a	0
local	0
surveillance	0
of	0
serious	0
adverse	0
events	0
.	0

BACKGR0UND	0
:	0
Spontaneous	0
reporting	0
systems	0
for	0
adverse	0
drug	0
reactions	0
(	0
ADRs	0
)	0
are	0
handicapped	0
by	0
under	0
-	0
reporting	0
and	0
limited	0
detail	0
on	0
individual	0
cases	0
.	0

We	0
report	0
an	0
investigation	0
from	0
a	0
local	0
surveillance	0
for	0
serious	0
adverse	0
drug	0
reactions	0
associated	0
with	0
disease	0
modifying	0
anti	0
-	0
rheumatic	0
drugs	0
that	0
was	0
triggered	0
by	0
the	0
occurrence	0
of	0
liver	3
failure	4
in	0
two	0
of	0
our	0
patients	0
.	0

METH0DS	0
:	0
Serious	0
ADR	0
reports	0
have	0
been	0
solicited	0
from	0
local	0
clinicians	0
by	0
regular	0
postcards	0
over	0
the	0
past	0
seven	0
years	0
.	0

Patients	0
'	0
,	0
who	0
had	0
hepatotoxicity	3
on	0
sulfasalazine	1
and	0
met	0
a	0
definition	0
of	0
a	0
serious	0
ADR	0
,	0
were	0
identified	0
.	0

Two	0
clinicians	0
reviewed	0
structured	0
case	0
reports	0
and	0
assessed	0
causality	0
by	0
consensus	0
and	0
by	0
using	0
a	0
causality	0
assessment	0
instrument	0
.	0

The	0
likely	0
frequency	0
of	0
hepatotoxicity	3
with	0
sulfasalazine	1
was	0
estimated	0
by	0
making	0
a	0
series	0
of	0
conservative	0
assumptions	0
.	0

RESULTS	0
:	0
Ten	0
cases	0
were	0
identified	0
:	0
eight	0
occurred	0
during	0
surveillance	0
.	0

Eight	0
patients	0
were	0
hospitalised	0
,	0
two	0
in	0
hepatic	3
failure	4
-	0
one	0
died	0
after	0
a	0
liver	0
transplant	0
.	0

All	0
but	0
one	0
event	0
occurred	0
within	0
6	0
weeks	0
of	0
treatment	0
.	0

Seven	0
patients	0
had	0
a	0
skin	3
rash	4
,	0
three	0
eosinophilia	3
and	0
one	0
interstitial	3
nephritis	4
.	0

Five	0
patients	0
were	0
of	0
Black	0
British	0
of	0
African	0
or	0
Caribbean	0
descent	0
.	0

Liver	0
enzymes	0
showed	0
a	0
hepatocellular	0
pattern	0
in	0
four	0
cases	0
and	0
a	0
mixed	0
pattern	0
in	0
six	0
.	0

Drug	0
-	0
related	0
hepatotoxicity	3
was	0
judged	0
probable	0
or	0
highly	0
probable	0
in	0
8	0
patients	0
.	0

The	0
likely	0
frequency	0
of	0
serious	0
hepatotoxicity	3
with	0
sulfasalazine	1
was	0
estimated	0
at	0
0	0
.	0
4	0
%	0
of	0
treated	0
patients	0
.	0

C0NCLUSI0N	0
:	0
Serious	0
hepatotoxicity	3
associated	0
with	0
sulfasalazine	1
appears	0
to	0
be	0
under	0
-	0
appreciated	0
and	0
intensive	0
monitoring	0
and	0
vigilance	0
in	0
the	0
first	0
6	0
weeks	0
of	0
treatment	0
is	0
especially	0
important	0
.	0

Complete	0
atrioventricular	3
block	4
secondary	0
to	0
lithium	1
therapy	0
.	0

Sinus	3
node	4
dysfunction	4
has	0
been	0
reported	0
most	0
frequently	0
among	0
the	0
adverse	0
cardiovascular	0
effects	0
of	0
lithium	1
.	0

In	0
the	0
present	0
case	0
,	0
complete	0
atrioventricular	3
(	4
AV	4
)	4
block	4
with	0
syncopal	3
attacks	4
developed	0
secondary	0
to	0
lithium	1
therapy	0
,	0
necessitating	0
permanent	0
pacemaker	0
implantation	0
.	0

Serum	0
lithium	1
levels	0
remained	0
under	0
or	0
within	0
the	0
therapeutic	0
range	0
during	0
the	0
syncopal	3
attacks	4
.	0

Lithium	1
should	0
be	0
used	0
with	0
extreme	0
caution	0
,	0
especially	0
in	0
patients	0
with	0
mild	0
disturbance	0
of	0
AV	0
conduction	0
.	0

Exaggerated	0
expression	0
of	0
inflammatory	0
mediators	0
in	0
vasoactive	0
intestinal	0
polypeptide	0
knockout	0
(	0
VIP	0
-	0
/	0
-	0
)	0
mice	0
with	0
cyclophosphamide	1
(	0
CYP	1
)	0
-	0
induced	0
cystitis	3
.	0

Vasoactive	0
intestinal	0
polypeptide	0
(	0
VIP	0
)	0
is	0
an	0
immunomodulatory	0
neuropeptide	0
distributed	0
in	0
micturition	0
pathways	0
.	0

VIP	0
(	0
-	0
/	0
-	0
)	0
mice	0
exhibit	0
altered	0
bladder	0
function	0
and	0
neurochemical	0
properties	0
in	0
micturition	0
pathways	0
after	0
cyclophosphamide	1
(	0
CYP	1
)	0
-	0
induced	0
cystitis	3
.	0

Given	0
VIP	0
'	0
s	0
role	0
as	0
an	0
anti	0
-	0
inflammatory	0
mediator	0
,	0
we	0
hypothesized	0
that	0
VIP	0
(	0
-	0
/	0
-	0
)	0
mice	0
would	0
exhibit	0
enhanced	0
inflammatory	0
mediator	0
expression	0
after	0
cystitis	3
.	0

A	0
mouse	0
inflammatory	0
cytokine	0
and	0
receptor	0
RT2	0
profiler	0
array	0
was	0
used	0
to	0
determine	0
regulated	0
transcripts	0
in	0
the	0
urinary	0
bladder	0
of	0
wild	0
type	0
(	0
WT	0
)	0
and	0
VIP	0
(	0
-	0
/	0
-	0
)	0
mice	0
with	0
or	0
without	0
CYP	1
-	0
induced	0
cystitis	3
(	0
150	0
mg	0
/	0
kg	0
;	0
i	0
.	0
p	0
.	0
;	0
48	0
h	0
)	0
.	0

Four	0
binary	0
comparisons	0
were	0
made	0
:	0
WT	0
control	0
versus	0
CYP	1
treatment	0
(	0
48	0
h	0
)	0
,	0
VIP	0
(	0
-	0
/	0
-	0
)	0
control	0
versus	0
CYP	1
treatment	0
(	0
48	0
h	0
)	0
,	0
WT	0
control	0
versus	0
VIP	0
(	0
-	0
/	0
-	0
)	0
control	0
,	0
and	0
WT	0
with	0
CYP	1
treatment	0
(	0
48	0
h	0
)	0
versus	0
VIP	0
(	0
-	0
/	0
-	0
)	0
with	0
CYP	1
treatment	0
(	0
48	0
h	0
)	0
.	0

The	0
genes	0
presented	0
represent	0
(	0
1	0
)	0
greater	0
than	0
1	0
.	0
5	0
-	0
fold	0
change	0
in	0
either	0
direction	0
and	0
(	0
2	0
)	0
the	0
p	0
value	0
is	0
less	0
than	0
0	0
.	0
05	0
for	0
the	0
comparison	0
being	0
made	0
.	0

Several	0
regulated	0
genes	0
were	0
validated	0
using	0
enzyme	0
-	0
linked	0
immunoassays	0
including	0
IL	0
-	0
1beta	0
and	0
CXCL1	0
.	0

CYP	1
treatment	0
significantly	0
(	0
p	0
<	0
or	0
=	0
0	0
.	0
001	0
)	0
increased	0
expression	0
of	0
CXCL1	0
and	0
IL	0
-	0
1beta	0
in	0
the	0
urinary	0
bladder	0
of	0
WT	0
and	0
VIP	0
(	0
-	0
/	0
-	0
)	0
mice	0
,	0
but	0
expression	0
in	0
VIP	0
(	0
-	0
/	0
-	0
)	0
mice	0
with	0
CYP	1
treatment	0
was	0
significantly	0
(	0
p	0
<	0
or	0
=	0
0	0
.	0
001	0
)	0
greater	0
(	0
4	0
.	0
2	0
-	0
to	0
13	0
-	0
fold	0
increase	0
)	0
than	0
that	0
observed	0
in	0
WT	0
urinary	0
bladder	0
(	0
3	0
.	0
6	0
-	0
to	0
5	0
-	0
fold	0
increase	0
)	0
.	0

The	0
data	0
suggest	0
that	0
in	0
VIP	0
(	0
-	0
/	0
-	0
)	0
mice	0
with	0
bladder	3
inflammation	4
,	0
inflammatory	0
mediators	0
are	0
increased	0
above	0
that	0
observed	0
in	0
WT	0
with	0
CYP	1
.	0

This	0
shift	0
in	0
balance	0
may	0
contribute	0
to	0
increased	0
bladder	3
dysfunction	4
in	0
VIP	0
(	0
-	0
/	0
-	0
)	0
mice	0
with	0
bladder	3
inflammation	4
and	0
altered	0
neurochemical	0
expression	0
in	0
micturition	0
pathways	0
.	0

Debrisoquine	1
phenotype	0
and	0
the	0
pharmacokinetics	0
and	0
beta	0
-	0
2	0
receptor	0
pharmacodynamics	0
of	0
metoprolol	1
and	0
its	0
enantiomers	0
.	0

The	0
metabolism	0
of	0
the	0
cardioselective	0
beta	0
-	0
blocker	0
metoprolol	1
is	0
under	0
genetic	0
control	0
of	0
the	0
debrisoquine	1
/	0
sparteine	1
type	0
.	0

The	0
two	0
metabolic	0
phenotypes	0
,	0
extensive	0
(	0
EM	0
)	0
and	0
poor	0
metabolizers	0
(	0
PM	0
)	0
,	0
show	0
different	0
stereoselective	0
metabolism	0
,	0
resulting	0
in	0
apparently	0
higher	0
beta	0
-	0
1	0
adrenoceptor	0
antagonistic	0
potency	0
of	0
racemic	0
metoprolol	1
in	0
EMs	0
.	0

We	0
investigated	0
if	0
the	0
latter	0
also	0
applies	0
to	0
the	0
beta	0
-	0
2	0
adrenoceptor	0
antagonism	0
by	0
metoprolol	1
.	0

The	0
drug	0
effect	0
studied	0
was	0
the	0
antagonism	0
by	0
metoprolol	1
of	0
terbutaline	1
-	0
induced	0
hypokalemia	3
.	0

By	0
using	0
pharmacokinetic	0
pharmacodynamic	0
modeling	0
the	0
pharmacodynamics	0
of	0
racemic	0
metoprolol	1
and	0
the	0
active	0
S	0
-	0
isomer	0
,	0
were	0
quantitated	0
in	0
EMs	0
and	0
PMs	0
in	0
terms	0
of	0
IC50	0
values	0
,	0
representing	0
metoprolol	1
plasma	0
concentrations	0
resulting	0
in	0
half	0
-	0
maximum	0
receptor	0
occupancy	0
.	0

Six	0
EMs	0
received	0
0	0
.	0
5	0
mg	0
of	0
terbutaline	1
s	0
.	0
c	0
.	0
on	0
two	0
different	0
occasions	0
:	0
1	0
)	0
1	0
hr	0
after	0
administration	0
of	0
a	0
placebo	0
and	0
2	0
)	0
1	0
hr	0
after	0
150	0
mg	0
of	0
metoprolol	1
p	0
.	0
o	0
.	0

Five	0
PMs	0
were	0
studied	0
according	0
to	0
the	0
same	0
protocol	0
,	0
except	0
for	0
a	0
higher	0
terbutaline	1
dose	0
(	0
0	0
.	0
75	0
mg	0
)	0
on	0
day	0
2	0
.	0

Blood	0
samples	0
for	0
the	0
analysis	0
of	0
plasma	0
potassium	1
,	0
terbutaline	1
,	0
metoprolol	1
(	0
racemic	0
,	0
R	0
-	0
and	0
S	0
-	0
isomer	0
)	0
,	0
and	0
alpha	1
-	2
hydroxymetoprolol	2
concentrations	0
were	0
taken	0
at	0
regular	0
time	0
intervals	0
,	0
during	0
8	0
hr	0
after	0
metoprolol	1
.	0

In	0
PMs	0
,	0
metoprolol	1
increased	0
the	0
terbutaline	1
area	0
under	0
the	0
plasma	0
concentration	0
vs	0
.	0
time	0
curve	0
(	0
+	0
67	0
%	0
)	0
.	0

Higher	0
metoprolol	1
/	0
alpha	1
-	2
hydroxymetoprolol	2
ratios	0
in	0
PMs	0
were	0
predictive	0
for	0
higher	0
R	0
-	0
/	0
S	0
-	0
isomer	0
ratios	0
of	0
unchanged	0
drug	0
.	0

There	0
was	0
a	0
difference	0
in	0
metoprolol	1
potency	0
with	0
higher	0
racemic	0
metoprolol	1
IC50	0
values	0
in	0
PMs	0
(	0
72	0
+	0
/	0
-	0
7	0
ng	0
.	0
ml	0
-	0
1	0
)	0
than	0
EMs	0
(	0
42	0
+	0
/	0
-	0
8	0
ng	0
.	0
ml	0
-	0
1	0
,	0
P	0
less	0
than	0
.	0
001	0
)	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

The	0
hemodynamics	0
of	0
oxytocin	1
and	0
other	0
vasoactive	0
agents	0
during	0
neuraxial	0
anesthesia	0
for	0
cesarean	0
delivery	0
:	0
findings	0
in	0
six	0
cases	0
.	0

0xytocin	1
is	0
a	0
commonly	0
used	0
uterotonic	0
that	0
can	0
cause	0
significant	0
and	0
even	0
fatal	0
hypotension	3
,	0
particularly	0
when	0
given	0
as	0
a	0
bolus	0
.	0

The	0
resulting	0
hypotension	3
can	0
be	0
produced	0
by	0
a	0
decrease	0
in	0
systemic	0
vascular	0
resistance	0
or	0
cardiac	0
output	0
through	0
a	0
decrease	0
in	0
venous	0
return	0
.	0

Parturients	0
with	0
normal	0
volume	0
status	0
,	0
heart	0
valves	0
and	0
pulmonary	0
vasculature	0
most	0
often	0
respond	0
to	0
this	0
hypotension	3
with	0
a	0
compensatory	0
increase	0
in	0
heart	0
rate	0
and	0
stroke	3
volume	0
.	0

0xytocin	1
-	0
induced	0
hypotension	3
at	0
cesarean	0
delivery	0
may	0
be	0
incorrectly	0
attributed	0
to	0
blood	3
loss	4
.	0

Pulse	0
power	0
analysis	0
(	0
also	0
called	0
"	0
pulse	0
contour	0
analysis	0
"	0
)	0
of	0
an	0
arterial	0
pressure	0
wave	0
form	0
allows	0
continuous	0
evaluation	0
of	0
systemic	0
vascular	0
resistance	0
and	0
cardiac	0
output	0
in	0
real	0
time	0
,	0
thereby	0
elucidating	0
the	0
causative	0
factors	0
behind	0
changes	0
in	0
blood	0
pressure	0
.	0

Pulse	0
power	0
analysis	0
was	0
conducted	0
in	0
six	0
cases	0
of	0
cesarean	0
delivery	0
performed	0
under	0
neuraxial	0
anesthesia	0
.	0

Hypotension	3
in	0
response	0
to	0
oxytocin	1
was	0
associated	0
with	0
a	0
decrease	0
in	0
systemic	0
vascular	0
resistance	0
and	0
a	0
compensatory	0
increase	0
in	0
stroke	3
volume	0
,	0
heart	0
rate	0
and	0
cardiac	0
output	0
.	0

Pulse	0
power	0
analysis	0
may	0
be	0
helpful	0
in	0
determining	0
the	0
etiology	0
of	0
and	0
treating	0
hypotension	3
during	0
cesarean	0
delivery	0
under	0
neuraxial	0
anesthesia	0
.	0

Protective	0
effects	0
of	0
antithrombin	0
on	0
puromycin	1
aminonucleoside	2
nephrosis	3
in	0
rats	0
.	0

We	0
investigated	0
the	0
effects	0
of	0
antithrombin	0
,	0
a	0
plasma	0
inhibitor	0
of	0
coagulation	0
factors	0
,	0
in	0
rats	0
with	0
puromycin	1
aminonucleoside	2
-	0
induced	0
nephrosis	3
,	0
which	0
is	0
an	0
experimental	0
model	0
of	0
human	0
nephrotic	3
syndrome	4
.	0

Antithrombin	0
(	0
50	0
or	0
500	0
IU	0
/	0
kg	0
/	0
i	0
.	0
v	0
.	0
)	0
was	0
administered	0
to	0
rats	0
once	0
a	0
day	0
for	0
10	0
days	0
immediately	0
after	0
the	0
injection	0
of	0
puromycin	1
aminonucleoside	2
(	0
50	0
mg	0
/	0
kg	0
/	0
i	0
.	0
v	0
.	0
)	0
.	0

Treatment	0
with	0
antithrombin	0
attenuated	0
the	0
puromycin	1
aminonucleoside	2
-	0
induced	0
hematological	3
abnormalities	4
.	0

Puromycin	1
aminonucleoside	2
-	0
induced	0
renal	3
dysfunction	4
and	0
hyperlipidemia	3
were	0
also	0
suppressed	0
.	0

Histopathological	0
examination	0
revealed	0
severe	0
renal	3
damage	4
such	0
as	0
proteinaceous	0
casts	0
in	0
tubuli	0
and	0
tubular	0
expansion	0
in	0
the	0
kidney	0
of	0
control	0
rats	0
,	0
while	0
an	0
improvement	0
of	0
the	0
damage	0
was	0
seen	0
in	0
antithrombin	0
-	0
treated	0
rats	0
.	0

In	0
addition	0
,	0
antithrombin	0
treatment	0
markedly	0
suppressed	0
puromycin	1
aminonucleoside	2
-	0
induced	0
apoptosis	0
of	0
renal	0
tubular	0
epithelial	0
cells	0
.	0

Furthermore	0
,	0
puromycin	1
aminonucleoside	2
-	0
induced	0
increases	0
in	0
renal	0
cytokine	0
content	0
were	0
also	0
decreased	0
.	0

These	0
findings	0
suggest	0
that	0
thrombin	0
plays	0
an	0
important	0
role	0
in	0
the	0
pathogenesis	0
of	0
puromycin	1
aminonucleoside	2
-	0
induced	0
nephrotic	3
syndrome	4
.	0

Treatment	0
with	0
antithrombin	0
may	0
be	0
clinically	0
effective	0
in	0
patients	0
with	0
nephrotic	3
syndrome	4
.	0

Heparin	1
-	0
induced	0
thrombocytopenia	3
after	0
liver	0
transplantation	0
.	0

BACKGR0UND	0
:	0
Unfractionated	1
heparin	2
sodium	2
(	0
UFH	1
)	0
or	0
low	1
-	2
molecular	2
weight	2
heparin	2
(	0
LMWH	0
)	0
is	0
used	0
in	0
anticoagulant	0
protocols	0
at	0
several	0
institutions	0
to	0
prevent	0
thrombosis	3
after	0
liver	0
transplantation	0
.	0

Heparin	1
-	0
induced	0
thrombocytopenia	3
(	0
HIT	3
)	0
is	0
an	0
adverse	0
immune	0
-	0
mediated	0
reaction	0
to	0
heparin	1
,	0
resulting	0
in	0
platelet	0
count	0
decreases	0
of	0
more	0
than	0
50	0
%	0
.	0

The	0
frequencies	0
of	0
HIT	3
after	0
liver	0
transplantation	0
and	0
platelet	0
factor	0
4	0
/	0
heparin	1
-	0
reactive	0
antibody	0
(	0
HIT	3
antibody	0
)	0
positivity	0
in	0
liver	0
transplantation	0
patients	0
,	0
however	0
,	0
are	0
unknown	0
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
The	0
32	0
men	0
and	0
20	0
women	0
underwent	0
living	0
donor	0
liver	0
transplantation	0
.	0

We	0
started	0
LMWH	0
(	0
25	0
IU	0
/	0
kg	0
/	0
h	0
)	0
on	0
postoperative	0
day	0
(	0
P0D	0
)	0
1	0
,	0
switching	0
to	0
UFH	1
(	0
5000	0
U	0
/	0
d	0
)	0
on	0
P0D	0
2	0
or	0
3	0
.	0

The	0
dose	0
of	0
UFH	1
was	0
changed	0
according	0
to	0
the	0
activated	0
clotting	0
time	0
level	0
.	0

HIT	3
antibody	0
levels	0
were	0
measured	0
the	0
day	0
before	0
surgery	0
and	0
on	0
P0D	0
7	0
and	0
14	0
.	0

Platelet	0
count	0
was	0
measured	0
daily	0
for	0
3	0
weeks	0
.	0

RESULTS	0
:	0
The	0
average	0
platelet	0
counts	0
preoperatively	0
,	0
and	0
on	0
P0D	0
7	0
,	0
14	0
,	0
and	0
21	0
were	0
65	0
,	0
88	0
,	0
149	0
,	0
and	0
169	0
x	0
10	0
(	0
9	0
)	0
/	0
L	0
,	0
respectively	0
.	0

Two	0
patients	0
developed	0
hepatic	0
artery	0
thrombosis	3
on	0
P0D	0
11	0
and	0
19	0
,	0
respectively	0
,	0
although	0
they	0
were	0
HIT	3
antibody	0
-	0
negative	0
and	0
their	0
platelet	0
counts	0
were	0
stable	0
.	0

In	0
2	0
other	0
patients	0
,	0
the	0
platelet	0
count	0
decreased	0
suddenly	0
from	0
107	0
x	0
10	0
(	0
9	0
)	0
/	0
L	0
on	0
P0D	0
4	0
to	0
65	0
x	0
10	0
(	0
9	0
)	0
/	0
L	0
on	0
P0D	0
6	0
and	0
from	0
76	0
x	0
10	0
(	0
9	0
)	0
/	0
L	0
on	0
P0D	0
7	0
to	0
33	0
x	0
10	0
(	0
9	0
)	0
/	0
L	0
on	0
P0D	0
9	0
,	0
respectively	0
.	0

The	0
heparin	1
-	0
induced	0
platelet	3
aggregation	4
test	0
was	0
negative	0
in	0
these	0
patients	0
.	0

The	0
percentage	0
of	0
HIT	3
antibody	0
-	0
positive	0
patients	0
was	0
0	0
.	0
5	0
%	0
preoperatively	0
,	0
5	0
.	0
6	0
%	0
on	0
P0D	0
7	0
,	0
and	0
5	0
.	0
6	0
%	0
on	0
P0D	0
14	0
.	0

None	0
of	0
the	0
subjects	0
/	0
patients	0
developed	0
UFH	1
-	0
related	0
HIT	3
.	0

C0NCLUSI0NS	0
:	0
In	0
our	0
series	0
,	0
the	0
occurrence	0
of	0
HIT	3
after	0
liver	0
transplantation	0
was	0
uncommon	0
.	0

Doxorubicin	1
cardiomyopathy	3
-	0
induced	0
inflammation	3
and	0
apoptosis	0
are	0
attenuated	0
by	0
gene	0
deletion	0
of	0
the	0
kinin	0
B1	0
receptor	0
.	0

Clinical	0
use	0
of	0
the	0
anthracycline	1
doxorubicin	1
(	0
D0X	1
)	0
is	0
limited	0
by	0
its	0
cardiotoxic	3
effects	0
,	0
which	0
are	0
attributed	0
to	0
the	0
induction	0
of	0
apoptosis	0
.	0

To	0
elucidate	0
the	0
possible	0
role	0
of	0
the	0
kinin	0
B1	0
receptor	0
(	0
B1R	0
)	0
during	0
the	0
development	0
of	0
D0X	1
cardiomyopathy	3
,	0
we	0
studied	0
B1R	0
knockout	0
mice	0
(	0
B1R	0
(	0
-	0
/	0
-	0
)	0
)	0
by	0
investigating	0
cardiac	0
inflammation	3
and	0
apoptosis	0
after	0
induction	0
of	0
D0X	1
-	0
induced	0
cardiomyopathy	3
.	0

D0X	1
control	0
mice	0
showed	0
cardiac	3
dysfunction	4
measured	0
by	0
pressure	0
-	0
volume	0
loops	0
in	0
vivo	0
.	0

This	0
was	0
associated	0
with	0
a	0
reduced	0
activation	0
state	0
of	0
AKT	0
,	0
as	0
well	0
as	0
an	0
increased	0
bax	0
/	0
bcl2	0
ratio	0
in	0
Western	0
blots	0
,	0
indicating	0
cardiac	3
apoptosis	4
.	0

Furthermore	0
,	0
mRNA	0
levels	0
of	0
the	0
proinflammatory	0
cytokine	0
interleukin	0
6	0
were	0
increased	0
in	0
the	0
cardiac	0
tissue	0
.	0

In	0
D0X	1
B1R	0
(	0
-	0
/	0
-	0
)	0
mice	0
,	0
cardiac	3
dysfunction	4
was	0
improved	0
compared	0
to	0
D0X	1
control	0
mice	0
,	0
which	0
was	0
associated	0
with	0
normalization	0
of	0
the	0
bax	0
/	0
bcl	0
-	0
2	0
ratio	0
and	0
interleukin	0
6	0
,	0
as	0
well	0
as	0
AKT	0
activation	0
state	0
.	0

These	0
findings	0
suggest	0
that	0
B1R	0
is	0
detrimental	0
in	0
D0X	1
cardiomyopathy	3
in	0
that	0
it	0
mediates	0
the	0
inflammatory	0
response	0
and	0
apoptosis	0
.	0

These	0
insights	0
might	0
have	0
useful	0
implications	0
for	0
future	0
studies	0
utilizing	0
B1R	0
antagonists	0
for	0
treatment	0
of	0
human	0
D0X	1
cardiomyopathy	3
.	0

Detailed	0
spectral	0
profile	0
analysis	0
of	0
penicillin	1
-	0
induced	0
epileptiform	3
activity	4
in	0
anesthetized	0
rats	0
.	0

Penicillin	1
model	0
is	0
a	0
widely	0
used	0
experimental	0
model	0
for	0
epilepsy	3
research	0
.	0

In	0
the	0
present	0
study	0
we	0
aimed	0
to	0
portray	0
a	0
detailed	0
spectral	0
analysis	0
of	0
penicillin	1
-	0
induced	0
epileptiform	3
activity	4
in	0
comparison	0
with	0
basal	0
brain	0
activity	0
in	0
anesthetized	0
Wistar	0
rats	0
.	0

Male	0
Wistar	0
rats	0
were	0
anesthetized	0
with	0
i	0
.	0
p	0
.	0
urethane	1
and	0
connected	0
to	0
an	0
electrocorticogram	0
setup	0
.	0

After	0
a	0
short	0
period	0
of	0
basal	0
activity	0
recording	0
,	0
epileptic	3
focus	0
was	0
induced	0
by	0
injecting	0
400IU	0
/	0
2	0
microl	0
penicillin	1
-	2
G	2
potassium	2
into	0
the	0
left	0
lateral	0
ventricle	0
while	0
the	0
cortical	0
activity	0
was	0
continuously	0
recorded	0
.	0

Basal	0
activity	0
,	0
latent	0
period	0
and	0
the	0
penicillin	1
-	0
induced	0
epileptiform	3
activity	4
periods	0
were	0
then	0
analyzed	0
using	0
both	0
conventional	0
methods	0
and	0
spectral	0
analysis	0
.	0

Spectral	0
analyses	0
were	0
conducted	0
by	0
dividing	0
the	0
whole	0
spectrum	0
into	0
different	0
frequency	0
bands	0
including	0
delta	0
,	0
theta	0
(	0
slow	0
and	0
fast	0
)	0
,	0
alpha	0
-	0
sigma	0
,	0
beta	0
(	0
1	0
and	0
2	0
)	0
and	0
gamma	0
(	0
1	0
and	0
2	0
)	0
bands	0
.	0

0ur	0
results	0
show	0
that	0
the	0
most	0
affected	0
frequency	0
bands	0
were	0
delta	0
,	0
theta	0
,	0
beta	0
-	0
2	0
and	0
gamma	0
-	0
2	0
bands	0
during	0
the	0
epileptiform	3
activity	4
and	0
there	0
were	0
marked	0
differences	0
in	0
terms	0
of	0
spectral	0
densities	0
between	0
three	0
investigated	0
episodes	0
(	0
basal	0
activity	0
,	0
latent	0
period	0
and	0
epileptiform	3
activity	4
)	0
.	0

0ur	0
results	0
may	0
help	0
to	0
analyze	0
novel	0
data	0
obtained	0
using	0
similar	0
experimental	0
models	0
and	0
the	0
simple	0
analysis	0
method	0
described	0
here	0
can	0
be	0
used	0
in	0
similar	0
studies	0
to	0
investigate	0
the	0
basic	0
neuronal	0
mechanism	0
of	0
this	0
or	0
other	0
types	0
of	0
experimental	0
epilepsies	3
.	0

High	0
fat	1
diet	0
-	0
fed	0
obese	3
rats	0
are	0
highly	0
sensitive	0
to	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
.	0

0ften	0
,	0
chemotherapy	0
by	0
doxorubicin	1
(	0
Adriamycin	1
)	0
is	0
limited	0
due	0
to	0
life	0
threatening	0
cardiotoxicity	3
in	0
patients	0
during	0
and	0
posttherapy	0
.	0

Recently	0
,	0
we	0
have	0
shown	0
that	0
moderate	0
diet	0
restriction	0
remarkably	0
protects	0
against	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
.	0

This	0
cardioprotection	0
is	0
accompanied	0
by	0
decreased	0
cardiac	0
oxidative	0
stress	0
and	0
triglycerides	1
and	0
increased	0
cardiac	0
fatty	0
-	0
acid	0
oxidation	0
,	0
ATP	1
synthesis	0
,	0
and	0
upregulated	0
JAK	0
/	0
STAT3	0
pathway	0
.	0

In	0
the	0
current	0
study	0
,	0
we	0
investigated	0
whether	0
a	0
physiological	0
intervention	0
by	0
feeding	0
40	0
%	0
high	0
fat	1
diet	0
(	0
HFD	0
)	0
,	0
which	0
induces	0
obesity	3
in	0
male	0
Sprague	0
-	0
Dawley	0
rats	0
(	0
250	0
-	0
275	0
g	0
)	0
,	0
sensitizes	0
to	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
.	0

A	0
LD	0
(	0
10	0
)	0
dose	0
(	0
8	0
mg	0
doxorubicin	1
/	0
kg	0
,	0
ip	0
)	0
administered	0
on	0
day	0
43	0
of	0
the	0
HFD	0
feeding	0
regimen	0
led	0
to	0
higher	0
cardiotoxicity	3
,	0
cardiac	3
dysfunction	4
,	0
lipid	0
peroxidation	0
,	0
and	0
80	0
%	0
mortality	0
in	0
the	0
obese	3
(	0
0B	3
)	0
rats	0
in	0
the	0
absence	0
of	0
any	0
significant	0
renal	3
or	4
hepatic	4
toxicity	4
.	0

Doxorubicin	1
toxicokinetics	0
studies	0
revealed	0
no	0
change	0
in	0
accumulation	0
of	0
doxorubicin	1
and	0
doxorubicinol	1
(	0
toxic	0
metabolite	0
)	0
in	0
the	0
normal	0
diet	0
-	0
fed	0
(	0
ND	0
)	0
and	0
0B	3
hearts	0
.	0

Mechanistic	0
studies	0
revealed	0
that	0
0B	3
rats	0
are	0
sensitized	0
due	0
to	0
:	0
(	0
1	0
)	0
higher	0
oxyradical	0
stress	0
leading	0
to	0
upregulation	0
of	0
uncoupling	0
proteins	0
2	0
and	0
3	0
,	0
(	0
2	0
)	0
downregulation	0
of	0
cardiac	0
peroxisome	0
proliferators	0
activated	0
receptor	0
-	0
alpha	0
,	0
(	0
3	0
)	0
decreased	0
plasma	0
adiponectin	0
levels	0
,	0
(	0
4	0
)	0
decreased	0
cardiac	0
fatty	0
-	0
acid	0
oxidation	0
(	0
666	0
.	0
9	0
+	0
/	0
-	0
14	0
.	0
0	0
nmol	0
/	0
min	0
/	0
g	0
heart	0
in	0
ND	0
versus	0
400	0
.	0
2	0
+	0
/	0
-	0
11	0
.	0
8	0
nmol	0
/	0
min	0
/	0
g	0
heart	0
in	0
0B	3
)	0
,	0
(	0
5	0
)	0
decreased	0
mitochondrial	0
AMP	1
-	0
alpha2	0
protein	0
kinase	0
,	0
and	0
(	0
6	0
)	0
86	0
%	0
drop	0
in	0
cardiac	0
ATP	1
levels	0
accompanied	0
by	0
decreased	0
ATP	1
/	0
ADP	1
ratio	0
after	0
doxorubicin	1
administration	0
.	0

Decreased	0
cardiac	0
erythropoietin	0
and	0
increased	0
S0CS3	0
further	0
downregulated	0
the	0
cardioprotective	0
JAK	0
/	0
STAT3	0
pathway	0
.	0

In	0
conclusion	0
,	0
HFD	0
-	0
induced	0
obese	3
rats	0
are	0
highly	0
sensitized	0
to	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
by	0
substantially	0
downregulating	0
cardiac	0
mitochondrial	0
ATP	1
generation	0
,	0
increasing	0
oxidative	0
stress	0
and	0
downregulating	0
the	0
JAK	0
/	0
STAT3	0
pathway	0
.	0

Isoproterenol	1
induces	0
primary	0
loss	0
of	0
dystrophin	0
in	0
rat	0
hearts	0
:	0
correlation	0
with	0
myocardial	3
injury	4
.	0

The	0
mechanism	0
of	0
isoproterenol	1
-	0
induced	0
myocardial	3
damage	4
is	0
unknown	0
,	0
but	0
a	0
mismatch	0
of	0
oxygen	1
supply	0
vs	0
.	0
demand	0
following	0
coronary	0
hypotension	3
and	0
myocardial	3
hyperactivity	4
is	0
the	0
best	0
explanation	0
for	0
the	0
complex	0
morphological	0
alterations	0
observed	0
.	0

Severe	0
alterations	0
in	0
the	0
structural	0
integrity	0
of	0
the	0
sarcolemma	0
of	0
cardiomyocytes	0
have	0
been	0
demonstrated	0
to	0
be	0
caused	0
by	0
isoproterenol	1
.	0

Taking	0
into	0
account	0
that	0
the	0
sarcolemmal	0
integrity	0
is	0
stabilized	0
by	0
the	0
dystrophin	0
-	0
glycoprotein	0
complex	0
(	0
DGC	0
)	0
that	0
connects	0
actin	0
and	0
laminin	0
in	0
contractile	0
machinery	0
and	0
extracellular	0
matrix	0
and	0
by	0
integrins	0
,	0
this	0
study	0
tests	0
the	0
hypothesis	0
that	0
isoproterenol	1
affects	0
sarcolemmal	0
stability	0
through	0
changes	0
in	0
the	0
DGC	0
and	0
integrins	0
.	0

We	0
found	0
different	0
sensitivity	0
of	0
the	0
DGC	0
and	0
integrin	0
to	0
isoproterenol	1
subcutaneous	0
administration	0
.	0

Immunofluorescent	0
staining	0
revealed	0
that	0
dystrophin	0
is	0
the	0
most	0
sensitive	0
among	0
the	0
structures	0
connecting	0
the	0
actin	0
in	0
the	0
cardiomyocyte	0
cytoskeleton	0
and	0
the	0
extracellular	0
matrix	0
.	0

The	0
sarcomeric	0
actin	0
dissolution	0
occurred	0
after	0
the	0
reduction	0
or	0
loss	0
of	0
dystrophin	0
.	0

Subsequently	0
,	0
after	0
lysis	0
of	0
myofilaments	0
,	0
gamma	0
-	0
sarcoglycan	0
,	0
beta	0
-	0
dystroglycan	0
,	0
beta1	0
-	0
integrin	0
,	0
and	0
laminin	0
alpha	0
-	0
2	0
expressions	0
were	0
reduced	0
followed	0
by	0
their	0
breakdown	0
,	0
as	0
epiphenomena	0
of	0
the	0
myocytolytic	0
process	0
.	0

In	0
conclusion	0
,	0
administration	0
of	0
isoproterenol	1
to	0
rats	0
results	0
in	0
primary	0
loss	0
of	0
dystrophin	0
,	0
the	0
most	0
sensitive	0
among	0
the	0
structural	0
proteins	0
that	0
form	0
the	0
DGC	0
that	0
connects	0
the	0
extracellular	0
matrix	0
and	0
the	0
cytoskeleton	0
in	0
cardiomyocyte	0
.	0

These	0
changes	0
,	0
related	0
to	0
ischaemic	3
injury	4
,	0
explain	0
the	0
severe	0
alterations	0
in	0
the	0
structural	0
integrity	0
of	0
the	0
sarcolemma	0
of	0
cardiomyocytes	0
and	0
hence	0
severe	0
and	0
irreversible	0
injury	0
induced	0
by	0
isoproterenol	1
.	0

Etiologic	0
factors	0
in	0
the	0
pathogenesis	0
of	0
liver	3
tumors	4
associated	0
with	0
oral	1
contraceptives	2
.	0

Within	0
the	0
last	0
several	0
years	0
,	0
previously	0
rare	0
liver	3
tumors	4
have	0
been	0
seen	0
in	0
young	0
women	0
using	0
oral	1
contraceptive	2
steroids	1
.	0

The	0
Registry	0
for	0
Liver	3
Tumors	4
Associated	0
with	0
0ral	1
Contraceptives	2
at	0
the	0
University	0
of	0
California	0
,	0
Irvine	0
,	0
has	0
clearly	0
identified	0
27	0
cases	0
.	0

The	0
recent	0
literature	0
contains	0
44	0
case	0
reports	0
.	0

Common	0
to	0
these	0
71	0
cases	0
has	0
been	0
a	0
histopathologic	0
diagnosis	0
of	0
focal	3
nodular	4
hyperplasia	4
,	0
adenoma	3
,	0
hamartoma	3
,	0
and	0
hepatoma	3
.	0

Significant	0
statistical	0
etiologic	0
factors	0
include	0
prolonged	0
uninterrupted	0
usage	0
of	0
oral	1
contraceptive	2
steroids	1
.	0

Eight	0
deaths	0
and	0
liver	0
rupture	3
in	0
18	0
patients	0
attest	0
to	0
the	0
seriousness	0
of	0
this	0
new	0
potentially	0
lethal	0
adverse	0
phenomenon	0
.	0

Ifosfamide	1
continuous	0
infusion	0
without	0
mesna	1
.	0

A	0
phase	0
I	0
trial	0
of	0
a	0
14	0
-	0
day	0
cycle	0
.	0

Twenty	0
patients	0
received	0
27	0
courses	0
of	0
ifosfamide	1
administered	0
as	0
a	0
24	0
-	0
hour	0
continuous	0
infusion	0
for	0
14	0
days	0
without	0
Mesna	1
.	0

The	0
goal	0
of	0
the	0
study	0
was	0
to	0
deliver	0
a	0
dose	0
rate	0
and	0
total	0
cumulative	0
dose	0
of	0
ifosfamide	1
that	0
would	0
be	0
comparable	0
to	0
standard	0
bolus	0
or	0
short	0
-	0
term	0
infusions	0
administered	0
with	0
Mesna	1
.	0

Dose	0
escalations	0
proceeded	0
from	0
200	0
to	0
300	0
,	0
400	0
,	0
450	0
,	0
500	0
,	0
and	0
550	0
mg	0
/	0
m2	0
/	0
d	0
.	0

Four	0
patients	0
developed	0
transient	0
microscopic	0
hematuria	3
at	0
400	0
,	0
450	0
,	0
and	0
500	0
mg	0
/	0
m2	0
/	0
d	0
.	0

There	0
were	0
no	0
instances	0
of	0
macroscopic	0
hematuria	3
.	0

At	0
550	0
mg	0
/	0
m2	0
/	0
d	0
,	0
three	0
patients	0
experienced	0
nonurologic	0
toxicity	3
;	0
confusion	3
(	0
1	0
)	0
,	0
nausea	3
(	0
1	0
)	0
,	0
and	0
Grade	0
2	0
leukopenia	3
(	0
1	0
)	0
.	0

The	0
recommended	0
dose	0
of	0
500	0
mg	0
/	0
m2	0
/	0
d	0
delivers	0
a	0
total	0
dose	0
of	0
7	0
g	0
/	0
m2	0
per	0
cycle	0
,	0
which	0
is	0
comparable	0
to	0
that	0
delivered	0
in	0
clinical	0
practice	0
for	0
bolus	0
or	0
short	0
-	0
term	0
infusion	0
.	0

Because	0
few	0
patients	0
received	0
multiple	0
courses	0
over	0
time	0
,	0
the	0
cumulative	0
effects	0
are	0
indeterminate	0
in	0
the	0
present	0
trial	0
.	0

The	0
frequency	0
and	0
predictability	0
of	0
hematuria	3
are	0
not	0
precise	0
,	0
and	0
at	0
least	0
daily	0
monitoring	0
by	0
urine	0
Hematest	0
is	0
essential	0
,	0
adding	0
Mesna	1
to	0
the	0
infusate	0
in	0
patients	0
with	0
persistent	0
hematuria	3
.	0

The	0
protracted	0
infusion	0
schedule	0
for	0
ifosfamide	1
permits	0
convenient	0
outpatient	0
administration	0
without	0
Mesna	1
and	0
reduces	0
the	0
drug	0
cost	0
of	0
clinical	0
usage	0
of	0
this	0
agent	0
by	0
up	0
to	0
890	0
per	0
cycle	0
.	0

Clinical	0
activity	0
was	0
demonstrated	0
in	0
a	0
single	0
patient	0
,	0
but	0
a	0
comparative	0
trial	0
of	0
standard	0
bolus	0
schedules	0
with	0
the	0
protracted	0
infusion	0
schedule	0
will	0
be	0
necessary	0
to	0
determine	0
if	0
the	0
clinical	0
effectiveness	0
of	0
the	0
drug	0
is	0
maintained	0
.	0

A	0
case	0
of	0
ventricular	3
tachycardia	4
related	0
to	0
caffeine	1
pretreatment	0
.	0

Suboptimal	0
seizure	3
duration	0
is	0
commonly	0
encountered	0
in	0
electroconvulsive	0
therapy	0
practice	0
,	0
especially	0
in	0
older	0
patients	0
with	0
higher	0
seizure	3
thresholds	0
.	0

Intravenous	0
caffeine	1
is	0
commonly	0
used	0
to	0
improve	0
seizure	3
duration	0
and	0
quality	0
in	0
such	0
patients	0
and	0
is	0
generally	0
well	0
tolerated	0
aside	0
from	0
occasional	0
reports	0
of	0
relatively	0
benign	0
ventricular	3
ectopy	4
.	0

We	0
describe	0
a	0
patient	0
with	0
no	0
previous	0
history	0
of	0
cardiac	3
disease	4
or	0
arrhythmia	3
who	0
developed	0
sustained	0
bigeminy	0
and	0
2	0
brief	0
runs	0
of	0
ventricular	3
tachycardia	4
after	0
caffeine	1
administration	0
.	0

Although	0
intravenous	0
caffeine	1
is	0
generally	0
well	0
tolerated	0
,	0
the	0
clinician	0
should	0
be	0
aware	0
of	0
the	0
potential	0
for	0
unpredictable	0
and	0
serious	0
ventricular	3
arrhythmias	4
.	0

Fatal	0
haemopericardium	3
and	0
gastrointestinal	3
haemorrhage	4
due	0
to	0
possible	0
interaction	0
of	0
cranberry	0
juice	0
with	0
warfarin	1
.	0

We	0
report	0
a	0
case	0
of	0
fatal	0
internal	0
haemorrhage	3
in	0
an	0
elderly	0
man	0
who	0
consumed	0
only	0
cranberry	0
juice	0
for	0
two	0
weeks	0
while	0
maintaining	0
his	0
usual	0
dosage	0
of	0
warfarin	1
.	0

We	0
propose	0
that	0
naturally	0
occurring	0
compounds	0
such	0
as	0
flavonoids	1
,	0
which	0
are	0
present	0
in	0
fruit	0
juices	0
,	0
may	0
increase	0
the	0
potency	0
of	0
warfarin	1
by	0
competing	0
for	0
the	0
enzymes	0
that	0
normally	0
inactivate	0
warfarin	1
.	0

While	0
traditionally	0
regarded	0
as	0
foodstuffs	0
,	0
consumption	0
of	0
fruit	0
juices	0
should	0
be	0
considered	0
when	0
patients	0
develop	0
adverse	0
drug	0
reactions	0
.	0

Effect	0
of	0
increasing	0
intraperitoneal	0
infusion	0
rates	0
on	0
bupropion	1
hydrochloride	2
-	0
induced	0
seizures	3
in	0
mice	0
.	0

BACKGR0UND	0
:	0
It	0
is	0
not	0
known	0
if	0
there	0
is	0
a	0
relationship	0
between	0
input	0
rate	0
and	0
incidence	0
of	0
bupropion	1
-	0
induced	0
seizures	3
.	0

This	0
is	0
important	0
,	0
since	0
different	0
controlled	0
release	0
formulations	0
of	0
bupropion	1
release	0
the	0
active	0
drug	0
at	0
different	0
rates	0
.	0

METH0DS	0
:	0
We	0
investigated	0
the	0
effect	0
of	0
varying	0
the	0
intraperitoneal	0
infusion	0
rates	0
of	0
bupropion	1
HCl	2
120	0
mg	0
/	0
kg	0
,	0
a	0
known	0
convulsive	3
dose	0
50	0
(	0
CD50	0
)	0
,	0
on	0
the	0
incidence	0
and	0
severity	0
of	0
bupropion	1
-	0
induced	0
convulsions	3
in	0
the	0
Swiss	0
albino	0
mice	0
.	0

A	0
total	0
of	0
69	0
mice	0
,	0
approximately	0
7	0
weeks	0
of	0
age	0
,	0
and	0
weighing	0
21	0
.	0
0	0
to	0
29	0
.	0
1	0
g	0
were	0
randomly	0
assigned	0
to	0
bupropion	1
HCl	2
120	0
mg	0
/	0
kg	0
treatment	0
by	0
intraperitoneal	0
(	0
IP	0
)	0
administration	0
in	0
7	0
groups	0
(	0
9	0
to	0
10	0
animals	0
per	0
group	0
)	0
.	0

Bupropion	1
HCl	2
was	0
infused	0
through	0
a	0
surgically	0
implanted	0
IP	0
dosing	0
catheter	0
with	0
infusions	0
in	0
each	0
group	0
of	0
0	0
min	0
,	0
15	0
min	0
,	0
30	0
min	0
,	0
60	0
min	0
,	0
90	0
min	0
,	0
120	0
min	0
,	0
and	0
240	0
min	0
.	0

The	0
number	0
,	0
time	0
of	0
onset	0
,	0
duration	0
and	0
the	0
intensity	0
of	0
the	0
convulsions	3
or	0
absence	0
of	0
convulsions	3
were	0
recorded	0
.	0

RESULTS	0
:	0
The	0
results	0
showed	0
that	0
IP	0
administration	0
of	0
bupropion	1
HCl	2
120	0
mg	0
/	0
kg	0
by	0
bolus	0
injection	0
induced	0
convulsions	3
in	0
6	0
out	0
of	0
10	0
mice	0
(	0
60	0
%	0
of	0
convulsing	0
mice	0
)	0
in	0
group	0
1	0
.	0

Logistic	0
regression	0
analysis	0
revealed	0
that	0
infusion	0
time	0
was	0
significant	0
(	0
p	0
=	0
0	0
.	0
0004	0
;	0
odds	0
ratio	0
=	0
0	0
.	0
974	0
)	0
and	0
increasing	0
the	0
IP	0
infusion	0
time	0
of	0
bupropion	1
HCl	2
120	0
mg	0
/	0
kg	0
was	0
associated	0
with	0
a	0
91	0
%	0
reduced	0
odds	0
of	0
convulsions	3
at	0
infusion	0
times	0
of	0
15	0
to	0
90	0
min	0
compared	0
to	0
bolus	0
injection	0
.	0

Further	0
increase	0
in	0
infusion	0
time	0
resulted	0
in	0
further	0
reduction	0
in	0
the	0
odds	0
of	0
convulsions	3
to	0
99	0
.	0
8	0
%	0
reduction	0
at	0
240	0
min	0
.	0

C0NCLUSI0N	0
:	0
In	0
conclusion	0
,	0
the	0
demonstration	0
of	0
an	0
inverse	0
relationship	0
between	0
infusion	0
time	0
of	0
a	0
fixed	0
and	0
convulsive	3
dose	0
of	0
bupropion	1
and	0
the	0
risk	0
of	0
convulsions	3
in	0
a	0
prospective	0
study	0
is	0
novel	0
.	0

Graft	3
-	4
versus	4
-	4
host	4
disease	4
prophylaxis	0
with	0
everolimus	1
and	0
tacrolimus	1
is	0
associated	0
with	0
a	0
high	0
incidence	0
of	0
sinusoidal	3
obstruction	4
syndrome	4
and	0
microangiopathy	3
:	0
results	0
of	0
the	0
EVTAC	0
trial	0
.	0

A	0
calcineurin	0
inhibitor	0
combined	0
with	0
methotrexate	1
is	0
the	0
standard	0
prophylaxis	0
for	0
graft	3
-	4
versus	4
-	4
host	4
disease	4
(	0
GVHD	3
)	0
after	0
allogeneic	0
hematopoietic	0
stem	0
cell	0
transplantation	0
(	0
HSCT	0
)	0
.	0

Everolimus	1
,	0
a	0
derivative	0
of	0
sirolimus	1
,	0
seems	0
to	0
mediate	0
antileukemia	0
effects	0
.	0

We	0
report	0
on	0
a	0
combination	0
of	0
everolimus	1
and	0
tacrolimus	1
in	0
24	0
patients	0
(	0
median	0
age	0
,	0
62	0
years	0
)	0
with	0
either	0
myelodysplastic	3
syndrome	4
(	0
MDS	3
;	0
n	0
=	0
17	0
)	0
or	0
acute	3
myeloid	4
leukemia	4
(	0
AML	3
;	0
n	0
=	0
7	0
)	0
undergoing	0
intensive	0
conditioning	0
followed	0
by	0
HSCT	0
from	0
related	0
(	0
n	0
=	0
4	0
)	0
or	0
unrelated	0
(	0
n	0
=	0
20	0
)	0
donors	0
.	0

All	0
patients	0
engrafted	0
,	0
and	0
only	0
1	0
patient	0
experienced	0
grade	0
IV	0
mucositis	3
.	0

Nine	0
patients	0
(	0
37	0
%	0
)	0
developed	0
acute	0
grade	0
II	0
-	0
IV	0
GVHD	3
,	0
and	0
11	0
of	0
17	0
evaluable	0
patients	0
(	0
64	0
%	0
)	0
developed	0
chronic	0
extensive	0
GVHD	3
.	0

Transplantation	3
-	4
associated	4
microangiopathy	4
(	0
TMA	3
)	0
occurred	0
in	0
7	0
patients	0
(	0
29	0
%	0
)	0
,	0
with	0
2	0
cases	0
of	0
acute	3
renal	4
failure	4
.	0

The	0
study	0
was	0
terminated	0
prematurely	0
because	0
an	0
additional	0
6	0
patients	0
(	0
25	0
%	0
)	0
developed	0
sinusoidal	3
obstruction	4
syndrome	4
(	0
S0S	3
)	0
,	0
which	0
was	0
fatal	0
in	0
2	0
cases	0
.	0

With	0
a	0
median	0
follow	0
-	0
up	0
of	0
26	0
months	0
,	0
the	0
2	0
-	0
year	0
overall	0
survival	0
rate	0
was	0
47	0
%	0
.	0

Although	0
this	0
new	0
combination	0
appears	0
to	0
be	0
effective	0
as	0
a	0
prophylactic	0
regimen	0
for	0
acute	0
GVHD	3
,	0
the	0
incidence	0
of	0
TMA	3
and	0
S0S	3
is	0
considerably	0
higher	0
than	0
seen	0
with	0
other	0
regimens	0
.	0

Longitudinal	0
assessment	0
of	0
air	0
conduction	0
audiograms	0
in	0
a	0
phase	0
III	0
clinical	0
trial	0
of	0
difluoromethylornithine	1
and	0
sulindac	1
for	0
prevention	0
of	0
sporadic	0
colorectal	3
adenomas	4
.	0

A	0
phase	0
III	0
clinical	0
trial	0
assessed	0
the	0
recurrence	0
of	0
adenomatous	3
polyps	4
after	0
treatment	0
for	0
36	0
months	0
with	0
difluoromethylornithine	1
(	0
DFM0	1
)	0
plus	0
sulindac	1
or	0
matched	0
placebos	0
.	0

Temporary	0
hearing	3
loss	4
is	0
a	0
known	0
toxicity	3
of	0
treatment	0
with	0
DFM0	1
,	0
thus	0
a	0
comprehensive	0
approach	0
was	0
developed	0
to	0
analyze	0
serial	0
air	0
conduction	0
audiograms	0
.	0

The	0
generalized	0
estimating	0
equation	0
method	0
estimated	0
the	0
mean	0
difference	0
between	0
treatment	0
arms	0
with	0
regard	0
to	0
change	0
in	0
air	0
conduction	0
pure	0
tone	0
thresholds	0
while	0
accounting	0
for	0
within	0
-	0
subject	0
correlation	0
due	0
to	0
repeated	0
measurements	0
at	0
frequencies	0
.	0

Based	0
on	0
290	0
subjects	0
,	0
there	0
was	0
an	0
average	0
difference	0
of	0
0	0
.	0
50	0
dB	0
between	0
subjects	0
treated	0
with	0
DFM0	1
plus	0
sulindac	1
compared	0
with	0
those	0
treated	0
with	0
placebo	0
(	0
95	0
%	0
confidence	0
interval	0
,	0
-	0
0	0
.	0
64	0
to	0
1	0
.	0
63	0
dB	0
;	0
P	0
=	0
0	0
.	0
39	0
)	0
,	0
adjusted	0
for	0
baseline	0
values	0
,	0
age	0
,	0
and	0
frequencies	0
.	0

In	0
the	0
normal	0
speech	0
range	0
of	0
500	0
to	0
3	0
,	0
000	0
Hz	0
,	0
an	0
estimated	0
difference	0
of	0
0	0
.	0
99	0
dB	0
(	0
-	0
0	0
.	0
17	0
to	0
2	0
.	0
14	0
dB	0
;	0
P	0
=	0
0	0
.	0
09	0
)	0
was	0
detected	0
.	0

Dose	0
intensity	0
did	0
not	0
add	0
information	0
to	0
models	0
.	0

There	0
were	0
14	0
of	0
151	0
(	0
9	0
.	0
3	0
%	0
)	0
in	0
the	0
DFM0	1
plus	0
sulindac	1
group	0
and	0
4	0
of	0
139	0
(	0
2	0
.	0
9	0
%	0
)	0
in	0
the	0
placebo	0
group	0
who	0
experienced	0
at	0
least	0
15	0
dB	0
hearing	0
reduction	0
from	0
baseline	0
in	0
2	0
or	0
more	0
consecutive	0
frequencies	0
across	0
the	0
entire	0
range	0
tested	0
(	0
P	0
=	0
0	0
.	0
02	0
)	0
.	0

Follow	0
-	0
up	0
air	0
conduction	0
done	0
at	0
least	0
6	0
months	0
after	0
end	0
of	0
treatment	0
showed	0
an	0
adjusted	0
mean	0
difference	0
in	0
hearing	0
thresholds	0
of	0
1	0
.	0
08	0
dB	0
(	0
-	0
0	0
.	0
81	0
to	0
2	0
.	0
96	0
dB	0
;	0
P	0
=	0
0	0
.	0
26	0
)	0
between	0
treatment	0
arms	0
.	0

There	0
was	0
no	0
significant	0
difference	0
in	0
the	0
proportion	0
of	0
subjects	0
in	0
the	0
DFM0	1
plus	0
sulindac	1
group	0
who	0
experienced	0
clinically	0
significant	0
hearing	3
loss	4
compared	0
with	0
the	0
placebo	0
group	0
.	0

The	0
estimated	0
attributable	0
risk	0
of	0
ototoxicity	3
from	0
exposure	0
to	0
the	0
drug	0
is	0
8	0
.	0
4	0
%	0
(	0
95	0
%	0
confidence	0
interval	0
,	0
-	0
2	0
.	0
0	0
%	0
to	0
18	0
.	0
8	0
%	0
;	0
P	0
=	0
0	0
.	0
12	0
)	0
.	0

There	0
is	0
a	0
<	0
2	0
dB	0
difference	0
in	0
mean	0
threshold	0
for	0
patients	0
treated	0
with	0
DFM0	1
plus	0
sulindac	1
compared	0
with	0
those	0
treated	0
with	0
placebo	0
.	0

Proteinase	0
3	0
-	0
antineutrophil	0
cytoplasmic	0
antibody	0
-	0
(	0
PR3	0
-	0
ANCA	0
)	0
positive	0
necrotizing	0
glomerulonephritis	3
after	0
restarting	0
sulphasalazine	1
treatment	0
.	0

A	0
59	0
-	0
year	0
-	0
old	0
woman	0
with	0
ulcerative	3
colitis	4
developed	0
red	3
eyes	4
,	0
pleural	3
effusion	4
,	0
eosinophilia	3
and	0
urinary	3
abnormalities	4
after	0
restarting	0
of	0
sulphasalazine	1
treatment	0
.	0

Light	0
microscopy	0
of	0
a	0
kidney	0
biopsy	0
revealed	0
segmental	3
necrotizing	4
glomerulonephritis	4
without	0
deposition	0
of	0
immunoglobulin	0
or	0
complement	0
.	0

Proteinase	0
3	0
-	0
antineutrophil	0
cytoplasmic	0
antibody	0
(	0
PR3	0
-	0
ANCA	0
)	0
titer	0
was	0
elevated	0
at	0
183	0
ELISA	0
units	0
(	0
EU	0
)	0
in	0
sera	0
(	0
normal	0
range	0
less	0
than	0
10	0
EU	0
)	0
,	0
myeloperoxidase	0
-	0
ANCA	0
was	0
negative	0
.	0

PR3	0
-	0
ANCA	0
titer	0
was	0
250	0
and	0
1	0
,	0
070	0
EU	0
in	0
pleural	3
effusions	4
on	0
right	0
and	0
left	0
side	0
,	0
respectively	0
.	0

Although	0
cessation	0
of	0
sulphasalazine	1
treatment	0
resulted	0
in	0
improvements	0
in	0
fever	3
,	0
red	3
eyes	4
,	0
chest	3
pain	4
,	0
titer	0
of	0
C	0
-	0
reactive	0
protein	0
and	0
volume	0
of	0
the	0
pleural	3
effusions	4
,	0
we	0
initiated	0
steroid	1
therapy	0
,	0
because	0
PR3	0
-	0
ANCA	0
titer	0
rose	0
to	0
320	0
EU	0
,	0
eosinophil	0
count	0
increased	0
to	0
1	0
,	0
100	0
cells	0
/	0
microl	0
,	0
and	0
the	0
pleural	3
effusion	4
remained	0
.	0

0ne	0
month	0
after	0
steroid	1
therapy	0
,	0
the	0
pleural	3
effusion	4
disappeared	0
,	0
and	0
PR3	0
-	0
ANCA	0
titer	0
normalized	0
3	0
months	0
later	0
.	0

This	0
case	0
suggests	0
that	0
sulphasalazine	1
can	0
induce	0
PR3	0
-	0
ANCA	0
-	0
positive	0
necrotizing	0
glomerulonephritis	3
.	0

Comparison	0
of	0
unilateral	0
pallidotomy	0
and	0
subthalamotomy	0
findings	0
in	0
advanced	0
idiopathic	3
Parkinson	4
'	4
s	4
disease	4
.	0

A	0
prospective	0
,	0
randomized	0
,	0
double	0
-	0
blind	0
pilot	0
study	0
to	0
compare	0
the	0
results	0
of	0
stereotactic	0
unilateral	0
pallidotomy	0
and	0
subthalamotomy	0
in	0
advanced	0
idiopathic	3
Parkinson	4
'	4
s	4
disease	4
(	0
PD	3
)	0
refractory	0
to	0
medical	0
treatment	0
was	0
designed	0
.	0

Ten	0
consecutive	0
patients	0
(	0
mean	0
age	0
,	0
58	0
.	0
4	0
+	0
/	0
-	0
6	0
.	0
8	0
years	0
;	0
7	0
men	0
,	0
3	0
women	0
)	0
with	0
similar	0
characteristics	0
at	0
the	0
duration	0
of	0
disease	0
(	0
mean	0
disease	0
time	0
,	0
8	0
.	0
4	0
+	0
/	0
-	0
3	0
.	0
5	0
years	0
)	0
,	0
disabling	0
motor	0
fluctuations	0
(	0
Hoehn	0
_	0
Yahr	0
stage	0
3	0
-	0
5	0
in	0
off	0
-	0
drug	0
phases	0
)	0
and	0
levodopa	1
-	0
induced	0
dyskinesias	3
were	0
selected	0
.	0

All	0
patients	0
had	0
bilateral	0
symptoms	0
and	0
their	0
levodopa	1
equivalent	0
dosing	0
were	0
analysed	0
.	0

Six	0
patients	0
were	0
operated	0
on	0
in	0
the	0
globus	0
pallidus	0
interna	0
(	0
GPi	0
)	0
and	0
four	0
in	0
the	0
subthalamic	0
nucleus	0
(	0
STN	0
)	0
.	0

Clinical	0
evaluation	0
included	0
the	0
use	0
of	0
the	0
Unified	0
Parkinson	3
'	4
s	4
Disease	4
Rating	0
Scale	0
(	0
UPDRS	0
)	0
,	0
Hoehn	0
_	0
Yahr	0
score	0
and	0
Schwab	0
England	0
activities	0
of	0
daily	0
living	0
(	0
ADL	0
)	0
score	0
in	0
'	0
on	0
'	0
-	0
and	0
'	0
off	0
'	0
-	0
drug	0
conditions	0
before	0
surgery	0
and	0
6	0
months	0
after	0
surgery	0
.	0

There	0
was	0
statistically	0
significant	0
improvement	0
in	0
all	0
contralateral	0
major	0
parkinsonian	3
motor	0
signs	0
in	0
all	0
patients	0
followed	0
for	0
6	0
months	0
.	0

Levodopa	1
equivalent	0
daily	0
intake	0
was	0
significantly	0
reduced	0
in	0
the	0
STN	0
group	0
.	0

Changes	0
in	0
UPDRS	0
,	0
Hoehn	0
_	0
Yahr	0
and	0
Schwab	0
England	0
ADL	0
scores	0
were	0
similar	0
in	0
both	0
groups	0
.	0

Cognitive	0
functions	0
were	0
unchanged	0
in	0
both	0
groups	0
.	0

Complications	0
were	0
observed	0
in	0
two	0
patients	0
:	0
one	0
had	0
a	0
left	0
homonymous	3
hemianopsia	4
after	0
pallidotomy	0
and	0
another	0
one	0
developed	0
left	0
hemiballistic	0
movements	0
3	0
days	0
after	0
subthalamotomy	0
which	0
partly	0
improved	0
within	0
1	0
month	0
with	0
Valproate	1
1000	0
mg	0
/	0
day	0
.	0

The	0
findings	0
of	0
this	0
study	0
suggest	0
that	0
lesions	0
of	0
the	0
unilateral	0
STN	0
and	0
GPi	0
are	0
equally	0
effective	0
treatment	0
for	0
patients	0
with	0
advanced	0
PD	3
refractory	0
to	0
medical	0
treatment	0
.	0

DSMM	0
XI	0
study	0
:	0
dose	0
definition	0
for	0
intravenous	0
cyclophosphamide	1
in	0
combination	0
with	0
bortezomib	1
/	0
dexamethasone	1
for	0
remission	0
induction	0
in	0
patients	0
with	0
newly	0
diagnosed	0
myeloma	3
.	0

A	0
clinical	0
trial	0
was	0
initiated	0
to	0
evaluate	0
the	0
recommended	0
dose	0
of	0
cyclophosphamide	1
in	0
combination	0
with	0
bortezomib	1
and	0
dexamethasone	1
as	0
induction	0
treatment	0
before	0
stem	0
cell	0
transplantation	0
for	0
younger	0
patients	0
with	0
newly	0
diagnosed	0
multiple	3
myeloma	4
(	0
MM	3
)	0
.	0

Thirty	0
patients	0
were	0
treated	0
with	0
three	0
21	0
-	0
day	0
cycles	0
of	0
bortezomib	1
1	0
.	0
3	0
mg	0
/	0
m	0
(	0
2	0
)	0
on	0
days	0
1	0
,	0
4	0
,	0
8	0
,	0
and	0
11	0
plus	0
dexamethasone	1
40	0
mg	0
on	0
the	0
day	0
of	0
bortezomib	1
injection	0
and	0
the	0
day	0
after	0
plus	0
cyclophosphamide	1
at	0
900	0
,	0
1	0
,	0
200	0
,	0
or	0
1	0
,	0
500	0
mg	0
/	0
m	0
(	0
2	0
)	0
on	0
day	0
1	0
.	0

The	0
maximum	0
tolerated	0
dose	0
of	0
cyclophosphamide	1
was	0
defined	0
as	0
900	0
mg	0
/	0
m	0
(	0
2	0
)	0
.	0

At	0
this	0
dose	0
level	0
,	0
92	0
%	0
of	0
patients	0
achieved	0
at	0
least	0
a	0
partial	0
response	0
.	0

The	0
overall	0
response	0
rate	0
[	0
complete	0
response	0
(	0
CR	0
)	0
plus	0
partial	0
response	0
(	0
PR	0
)	0
]	0
across	0
all	0
dose	0
levels	0
was	0
77	0
%	0
,	0
with	0
a	0
10	0
%	0
CR	0
rate	0
.	0

No	0
patient	0
experienced	0
progressive	0
disease	0
.	0

The	0
most	0
frequent	0
adverse	0
events	0
were	0
hematological	3
and	4
gastrointestinal	4
toxicities	4
as	0
well	0
as	0
neuropathy	3
.	0

The	0
results	0
suggest	0
that	0
bortezomib	1
in	0
combination	0
with	0
cyclophosphamide	1
at	0
900	0
mg	0
/	0
m	0
(	0
2	0
)	0
and	0
dexamethasone	1
is	0
an	0
effective	0
induction	0
treatment	0
for	0
patients	0
with	0
newly	0
diagnosed	0
MM	3
that	0
warrants	0
further	0
investigation	0
.	0

Naloxone	1
reversal	0
of	0
hypotension	3
due	0
to	0
captopril	1
overdose	3
.	0

The	0
hemodynamic	0
effects	0
of	0
captopril	1
and	0
other	0
angiotensin	1
-	2
converting	2
enzyme	2
inhibitors	2
may	0
be	0
mediated	0
by	0
the	0
endogenous	0
opioid	0
system	0
.	0

The	0
opioid	0
antagonist	0
naloxone	1
has	0
been	0
shown	0
to	0
block	0
or	0
reverse	0
the	0
hypotensive	3
actions	0
of	0
captopril	1
.	0

We	0
report	0
a	0
case	0
of	0
an	0
intentional	0
captopril	1
overdose	3
,	0
manifested	0
by	0
marked	0
hypotension	3
,	0
that	0
resolved	0
promptly	0
with	0
the	0
administration	0
of	0
naloxone	1
.	0

To	0
our	0
knowledge	0
,	0
this	0
is	0
the	0
first	0
reported	0
case	0
of	0
captopril	1
-	0
induced	0
hypotension	3
treated	0
with	0
naloxone	1
.	0

0ur	0
experience	0
demonstrates	0
a	0
possible	0
role	0
of	0
naloxone	1
in	0
the	0
reversal	0
of	0
hypotension	3
resulting	0
from	0
captopril	1
.	0

Identification	0
of	0
a	0
simple	0
and	0
sensitive	0
microplate	0
method	0
for	0
the	0
detection	0
of	0
oversulfated	0
chondroitin	1
sulfate	2
in	0
heparin	1
products	0
.	0

Heparin	1
is	0
a	0
commonly	0
implemented	0
anticoagulant	0
used	0
to	0
treat	0
critically	0
ill	0
patients	0
.	0

Recently	0
,	0
a	0
number	0
of	0
commercial	0
lots	0
of	0
heparin	1
products	0
were	0
found	0
to	0
be	0
contaminated	0
with	0
an	0
oversulfated	0
chondroitin	1
sulfate	2
(	0
0SCS	0
)	0
derivative	0
that	0
could	0
elicit	0
a	0
hypotensive	3
response	0
in	0
pigs	0
following	0
a	0
single	0
high	0
-	0
dose	0
infusion	0
.	0

Using	0
both	0
contaminated	0
heparin	1
products	0
and	0
the	0
synthetically	0
produced	0
derivative	0
,	0
we	0
showed	0
that	0
the	0
0SCS	0
produces	0
dose	0
-	0
dependent	0
hypotension	3
in	0
pigs	0
.	0

The	0
no	0
observed	0
effect	0
level	0
(	0
N0EL	0
)	0
for	0
this	0
contaminant	0
appears	0
to	0
be	0
approximately	0
1mg	0
/	0
kg	0
,	0
corresponding	0
to	0
a	0
contamination	0
level	0
of	0
approximately	0
3	0
%	0
.	0

We	0
also	0
demonstrated	0
that	0
0SCS	0
can	0
be	0
identified	0
in	0
heparin	1
products	0
using	0
a	0
simple	0
,	0
inexpensive	0
,	0
commercially	0
available	0
heparin	1
enzyme	0
immunoassay	0
(	0
EIA	0
)	0
kit	0
that	0
has	0
a	0
limit	0
of	0
detection	0
of	0
approximately	0
0	0
.	0
1	0
%	0
,	0
well	0
below	0
the	0
N0EL	0
.	0

This	0
kit	0
may	0
provide	0
a	0
useful	0
method	0
to	0
test	0
heparin	1
products	0
for	0
contamination	0
with	0
oversulfated	0
GAG	0
derivatives	0
.	0

5	1
flourouracil	2
-	0
induced	0
apical	3
ballooning	4
syndrome	4
:	0
a	0
case	0
report	0
.	0

The	0
apical	3
ballooning	4
syndrome	4
(	0
ABS	3
)	0
is	0
a	0
recently	0
described	0
stress	0
-	0
mediated	0
acute	3
cardiac	4
syndrome	4
characterized	0
by	0
transient	0
wall	0
-	0
motion	0
abnormalities	0
involving	0
the	0
apex	0
and	0
midventricle	0
with	0
hyperkinesis	3
of	0
the	0
basal	0
left	0
ventricular	0
(	0
LV	0
)	0
segments	0
without	0
obstructive	0
epicardial	3
coronary	4
disease	4
.	0

Cardiotoxicity	3
is	0
not	0
an	0
uncommon	0
adverse	0
effect	0
of	0
chemotherapeutic	0
agents	0
.	0

However	0
,	0
there	0
are	0
no	0
reports	0
of	0
ABS	3
secondary	0
to	0
chemotherapeutic	0
agents	0
.	0

We	0
describe	0
the	0
case	0
of	0
a	0
woman	0
who	0
developed	0
the	0
syndrome	0
after	0
chemotherapy	0
for	0
metastatic	0
cancer	3
.	0

A	0
79	0
-	0
year	0
-	0
old	0
woman	0
presented	0
with	0
typical	0
ischemic	3
chest	3
pain	4
,	0
elevated	0
cardiac	0
enzymes	0
with	0
significant	0
ST	0
-	0
segment	0
abnormalities	0
on	0
her	0
electrocardiogram	0
.	0

She	0
underwent	0
recent	0
chemotherapy	0
with	0
fluorouracil	1
for	0
metastatic	0
colorectal	3
cancer	4
.	0

Echocardiography	0
revealed	0
a	0
wall	0
-	0
motion	0
abnormality	0
involving	0
the	0
apical	0
and	0
periapical	0
segments	0
which	0
appeared	0
akinetic	3
.	0

Coronary	0
angiography	0
revealed	0
no	0
obstructive	0
coronary	0
lesions	0
.	0

The	0
patient	0
was	0
stabilized	0
with	0
medical	0
therapy	0
.	0

Four	0
weeks	0
later	0
she	0
remained	0
completely	0
asymptomatic	0
.	0

Echocardiogram	0
revealed	0
a	0
normal	0
ejection	0
fraction	0
and	0
a	0
resolution	0
of	0
the	0
apical	0
akinesis	3
.	0

Pathogenetic	0
mechanisms	0
of	0
cardiac	3
complications	4
in	0
cancer	3
patients	0
undergoing	0
chemotherapy	0
include	0
coronary	3
vasospasm	4
,	0
endothelial	0
damage	0
and	0
consequent	0
thrombus	3
formation	0
.	0

In	0
our	0
patient	0
,	0
both	0
supraphysiologic	0
levels	0
of	0
plasma	0
catecholamines	1
and	0
stress	0
related	0
neuropeptides	0
caused	0
by	0
cancer	3
diagnosis	0
as	0
well	0
as	0
chemotherapy	0
may	0
have	0
contributed	0
the	0
development	0
of	0
ABS	3
.	0

Rapid	0
reversal	0
of	0
anticoagulation	0
reduces	0
hemorrhage	3
volume	0
in	0
a	0
mouse	0
model	0
of	0
warfarin	1
-	0
associated	0
intracerebral	3
hemorrhage	4
.	0

Warfarin	1
-	0
associated	0
intracerebral	3
hemorrhage	4
(	0
W	0
-	0
ICH	3
)	0
is	0
a	0
severe	0
type	0
of	0
stroke	3
.	0

There	0
is	0
no	0
consensus	0
on	0
the	0
optimal	0
treatment	0
for	0
W	0
-	0
ICH	3
.	0

Using	0
a	0
mouse	0
model	0
,	0
we	0
tested	0
whether	0
the	0
rapid	0
reversal	0
of	0
anticoagulation	0
using	0
human	0
prothrombin	1
complex	2
concentrate	2
(	0
PCC	1
)	0
can	0
reduce	0
hemorrhagic	0
blood	0
volume	0
.	0

Male	0
CD	0
-	0
1	0
mice	0
were	0
treated	0
with	0
warfarin	1
(	0
2	0
mg	0
/	0
kg	0
over	0
24	0
h	0
)	0
,	0
resulting	0
in	0
a	0
mean	0
(	0
+	0
/	0
-	0
s	0
.	0
d	0
.	0
)	0
International	0
Normalized	0
Ratio	0
of	0
3	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
9	0
.	0

First	0
,	0
we	0
showed	0
that	0
an	0
intravenous	0
administration	0
of	0
human	0
PCC	1
rapidly	0
reversed	0
anticoagulation	0
in	0
mice	0
.	0

Second	0
,	0
a	0
stereotactic	0
injection	0
of	0
collagenase	0
was	0
administered	0
to	0
induce	0
hemorrhage	3
in	0
the	0
right	0
striatum	0
.	0

Forty	0
-	0
five	0
minutes	0
later	0
,	0
the	0
animals	0
were	0
randomly	0
treated	0
with	0
PCC	1
(	0
100	0
U	0
/	0
kg	0
)	0
or	0
saline	0
i	0
.	0
v	0
.	0
(	0
n	0
=	0
12	0
per	0
group	0
)	0
.	0

Twenty	0
-	0
four	0
hours	0
after	0
hemorrhage	3
induction	0
,	0
hemorrhagic	0
blood	0
volume	0
was	0
quantified	0
using	0
a	0
photometric	0
hemoglobin	0
assay	0
.	0

The	0
mean	0
hemorrhagic	0
blood	0
volume	0
was	0
reduced	0
in	0
PCC	1
-	0
treated	0
animals	0
(	0
6	0
.	0
5	0
+	0
/	0
-	0
3	0
.	0
1	0
microL	0
)	0
compared	0
with	0
saline	0
controls	0
(	0
15	0
.	0
3	0
+	0
/	0
-	0
11	0
.	0
2	0
microL	0
,	0
P	0
=	0
0	0
.	0
015	0
)	0
.	0

In	0
the	0
saline	0
group	0
,	0
45	0
%	0
of	0
the	0
mice	0
developed	0
large	0
hematomas	3
(	0
i	0
.	0
e	0
.	0
,	0
>	0
15	0
microL	0
)	0
.	0

In	0
contrast	0
,	0
such	0
extensive	0
lesions	0
were	0
never	0
found	0
in	0
the	0
PCC	1
group	0
.	0

We	0
provide	0
experimental	0
data	0
suggesting	0
PCC	1
to	0
be	0
an	0
effective	0
acute	0
treatment	0
for	0
W	0
-	0
ICH	3
in	0
terms	0
of	0
reducing	0
hemorrhagic	0
blood	0
volume	0
.	0

Future	0
studies	0
are	0
needed	0
to	0
assess	0
the	0
therapeutic	0
potential	0
emerging	0
from	0
our	0
finding	0
for	0
human	0
W	0
-	0
ICH	3
.	0

Long	0
term	0
hormone	0
therapy	0
for	0
perimenopausal	0
and	0
postmenopausal	0
women	0
.	0

BACKGR0UND	0
:	0
Hormone	0
therapy	0
(	0
HT	0
)	0
is	0
widely	0
used	0
for	0
controlling	0
menopausal	0
symptoms	0
and	0
has	0
also	0
been	0
used	0
for	0
the	0
management	0
and	0
prevention	0
of	0
cardiovascular	3
disease	4
,	0
osteoporosis	3
and	0
dementia	3
in	0
older	0
women	0
.	0

This	0
is	0
an	0
updated	0
version	0
of	0
the	0
original	0
Cochrane	0
review	0
first	0
published	0
in	0
2005	0
.	0

0BJECTIVES	0
:	0
To	0
assess	0
the	0
effect	0
of	0
long	0
-	0
term	0
HT	0
on	0
mortality	0
,	0
cardiovascular	0
outcomes	0
,	0
cancer	3
,	0
gallbladder	3
disease	4
,	0
cognition	0
,	0
fractures	3
and	0
quality	0
of	0
life	0
.	0

SEARCH	0
STRATEGY	0
:	0
We	0
searched	0
the	0
following	0
databases	0
to	0
November	0
2007	0
:	0
Trials	0
Register	0
of	0
the	0
Cochrane	0
Menstrual	3
Disorders	4
and	0
Subfertility	0
Group	0
,	0
Cochrane	0
Central	0
Register	0
of	0
Controlled	0
Trials	0
,	0
MEDLINE	0
,	0
EMBASE	0
,	0
Biological	0
Abstracts	0
.	0

Also	0
relevant	0
non	0
-	0
indexed	0
journals	0
and	0
conference	0
abstracts	0
.	0

SELECTI0N	0
CRITERIA	0
:	0
Randomised	0
double	0
-	0
blind	0
trials	0
of	0
HT	0
versus	0
placebo	0
,	0
taken	0
for	0
at	0
least	0
one	0
year	0
by	0
perimenopausal	0
or	0
postmenopausal	0
women	0
.	0

HT	0
included	0
oestrogens	1
,	0
with	0
or	0
without	0
progestogens	1
,	0
via	0
oral	0
,	0
transdermal	0
,	0
subcutaneous	0
or	0
transnasal	0
routes	0
.	0

DATA	0
C0LLECTI0N	0
AND	0
ANALYSIS	0
:	0
Two	0
authors	0
independently	0
assessed	0
trial	0
quality	0
and	0
extracted	0
data	0
.	0

MAIN	0
RESULTS	0
:	0
Nineteen	0
trials	0
involving	0
41	0
,	0
904	0
women	0
were	0
included	0
.	0

In	0
relatively	0
healthy	0
women	0
,	0
combined	0
continuous	0
HT	0
significantly	0
increased	0
the	0
risk	0
of	0
venous	3
thrombo	4
-	4
embolism	4
or	0
coronary	0
event	0
(	0
after	0
one	0
year	0
'	0
s	0
use	0
)	0
,	0
stroke	3
(	0
after	0
three	0
years	0
)	0
,	0
breast	3
cancer	4
and	0
gallbladder	3
disease	4
.	0

Long	0
-	0
term	0
oestrogen	1
-	0
only	0
HT	0
significantly	0
increased	0
the	0
risk	0
of	0
venous	3
thrombo	4
-	4
embolism	4
,	0
stroke	3
and	0
gallbladder	3
disease	4
(	0
after	0
one	0
to	0
two	0
years	0
,	0
three	0
years	0
and	0
seven	0
years	0
'	0
use	0
respectively	0
)	0
,	0
but	0
did	0
not	0
significantly	0
increase	0
the	0
risk	0
of	0
breast	3
cancer	4
.	0

The	0
only	0
statistically	0
significant	0
benefits	0
of	0
HT	0
were	0
a	0
decreased	0
incidence	0
of	0
fractures	3
and	0
(	0
for	0
combined	0
HT	0
)	0
colon	3
cancer	4
,	0
with	0
long	0
-	0
term	0
use	0
.	0

Among	0
women	0
aged	0
over	0
65	0
who	0
were	0
relatively	0
healthy	0
(	0
i	0
.	0
e	0
.	0
generally	0
fit	0
,	0
without	0
overt	0
disease	0
)	0
and	0
taking	0
continuous	0
combined	0
HT	0
,	0
there	0
was	0
a	0
statistically	0
significant	0
increase	0
in	0
the	0
incidence	0
of	0
dementia	3
.	0

Among	0
women	0
with	0
cardiovascular	3
disease	4
,	0
long	0
-	0
term	0
use	0
of	0
combined	0
continuous	0
HT	0
significantly	0
increased	0
the	0
risk	0
of	0
venous	3
thrombo	4
-	4
embolism	4
.	0
0ne	0
trial	0
analysed	0
subgroups	0
of	0
2839	0
relatively	0
healthy	0
50	0
to	0
59	0
year	0
old	0
women	0
taking	0
combined	0
continuous	0
HT	0
and	0
1637	0
taking	0
oestrogen	1
-	0
only	0
HT	0
,	0
versus	0
similar	0
-	0
sized	0
placebo	0
groups	0
.	0

The	0
only	0
significantly	0
increased	0
risk	0
reported	0
was	0
for	0
venous	3
thrombo	4
-	4
embolism	4
in	0
women	0
taking	0
combined	0
continuous	0
HT	0
:	0
their	0
absolute	0
risk	0
remained	0
low	0
,	0
at	0
less	0
than	0
1	0
/	0
500	0
.	0

However	0
,	0
this	0
study	0
was	0
not	0
powered	0
to	0
detect	0
differences	0
between	0
groups	0
of	0
younger	0
women	0
.	0

AUTH0RS	0
'	0
C0NCLUSI0NS	0
:	0
HT	0
is	0
not	0
indicated	0
for	0
the	0
routine	0
management	0
of	0
chronic	0
disease	0
.	0

We	0
need	0
more	0
evidence	0
on	0
the	0
safety	0
of	0
HT	0
for	0
menopausal	0
symptom	0
control	0
,	0
though	0
short	0
-	0
term	0
use	0
appears	0
to	0
be	0
relatively	0
safe	0
for	0
healthy	0
younger	0
women	0
.	0

Acute	3
renal	4
failure	4
in	0
patients	0
with	0
AIDS	3
on	0
tenofovir	1
while	0
receiving	0
prolonged	0
vancomycin	1
course	0
for	0
osteomyelitis	3
.	0

Renal	3
failure	4
developed	0
after	0
a	0
prolonged	0
course	0
of	0
vancomycin	1
therapy	0
in	0
2	0
patients	0
who	0
were	0
receiving	0
tenofovir	1
disoproxil	2
fumarate	2
as	0
part	0
of	0
an	0
antiretroviral	0
regimen	0
.	0

Tenofovir	1
has	0
been	0
implicated	0
in	0
the	0
development	0
of	0
Fanconi	3
syndrome	4
and	0
renal	3
insufficiency	4
because	0
of	0
its	0
effects	0
on	0
the	0
proximal	0
renal	0
tubule	0
.	0

Vancomycin	1
nephrotoxicity	3
is	0
infrequent	0
but	0
may	0
result	0
from	0
coadministration	0
with	0
a	0
nephrotoxic	3
agent	0
.	0

Clinicians	0
should	0
be	0
aware	0
that	0
tenofovir	1
may	0
raise	0
the	0
risk	0
of	0
renal	3
failure	4
during	0
prolonged	0
administration	0
of	0
vancomycin	1
.	0

Recurrent	0
dysosmia	3
induced	0
by	0
pyrazinamide	1
.	0

Pyrazinamide	1
can	0
have	0
adverse	0
effects	0
such	0
as	0
hepatic	3
toxicity	4
,	0
hyperuricemia	3
or	0
digestive	0
disorders	0
.	0

In	0
rare	0
cases	0
,	0
alterations	0
in	0
taste	0
and	0
smell	0
function	0
have	0
been	0
reported	0
for	0
pyrazinamide	1
when	0
combined	0
with	0
other	0
drugs	0
.	0

We	0
report	0
a	0
case	0
of	0
reversible	0
olfactory	3
disorder	4
related	0
to	0
pyrazinamide	1
in	0
a	0
woman	0
,	0
with	0
a	0
positive	0
rechallenge	0
.	0

The	0
patient	0
presented	0
every	0
day	0
a	0
sensation	0
of	0
smelling	0
something	0
burning	0
15	0
min	0
after	0
drug	0
intake	0
.	0

Dysosmia	3
disappeared	0
completely	0
after	0
pyrazinamide	1
withdrawal	0
and	0
recurred	0
after	0
its	0
rechallenge	0
.	0

The	0
case	0
was	0
reported	0
to	0
the	0
Tunisian	0
Centre	0
of	0
Pharmacovigilance	0
.	0

Mice	0
lacking	0
mPGES	0
-	0
1	0
are	0
resistant	0
to	0
lithium	1
-	0
induced	0
polyuria	3
.	0

Cyclooxygenase	0
-	0
2	0
activity	0
is	0
required	0
for	0
the	0
development	0
of	0
lithium	1
-	0
induced	0
polyuria	3
.	0

However	0
,	0
the	0
involvement	0
of	0
a	0
specific	0
,	0
terminal	0
prostaglandin	1
(	0
PG	1
)	0
isomerase	0
has	0
not	0
been	0
evaluated	0
.	0

The	0
present	0
study	0
was	0
undertaken	0
to	0
assess	0
lithium	1
-	0
induced	0
polyuria	3
in	0
mice	0
deficient	0
in	0
microsomal	0
prostaglandin	1
E	2
synthase	0
-	0
1	0
(	0
mPGES	0
-	0
1	0
)	0
.	0

A	0
2	0
-	0
wk	0
administration	0
of	0
LiCl	1
(	0
4	0
mmol	0
.	0
kg	0
(	0
-	0
1	0
)	0
.	0
day	0
(	0
-	0
1	0
)	0
ip	0
)	0
in	0
mPGES	0
-	0
1	0
+	0
/	0
+	0
mice	0
led	0
to	0
a	0
marked	0
polyuria	3
with	0
hyposmotic	0
urine	0
.	0

This	0
was	0
associated	0
with	0
elevated	0
renal	0
mPGES	0
-	0
1	0
protein	0
expression	0
and	0
increased	0
urine	0
PGE	1
(	2
2	2
)	2
excretion	0
.	0

In	0
contrast	0
,	0
mPGES	0
-	0
1	0
-	0
/	0
-	0
mice	0
were	0
largely	0
resistant	0
to	0
lithium	1
-	0
induced	0
polyuria	3
and	0
a	0
urine	0
concentrating	0
defect	0
,	0
accompanied	0
by	0
nearly	0
complete	0
blockade	0
of	0
high	0
urine	0
PGE	1
(	2
2	2
)	2
and	0
cAMP	0
output	0
.	0

Immunoblotting	0
,	0
immunohistochemistry	0
,	0
and	0
quantitative	0
(	0
q	0
)	0
RT	0
-	0
PCR	0
consistently	0
detected	0
a	0
significant	0
decrease	0
in	0
aquaporin	0
-	0
2	0
(	0
AQP2	0
)	0
protein	0
expression	0
in	0
both	0
the	0
renal	0
cortex	0
and	0
medulla	0
of	0
lithium	1
-	0
treated	0
+	0
/	0
+	0
mice	0
.	0

This	0
decrease	0
was	0
significantly	0
attenuated	0
in	0
the	0
-	0
/	0
-	0
mice	0
.	0

qRT	0
-	0
PCR	0
detected	0
similar	0
patterns	0
of	0
changes	0
in	0
AQP2	0
mRNA	0
in	0
the	0
medulla	0
but	0
not	0
in	0
the	0
cortex	0
.	0

Similarly	0
,	0
the	0
total	0
protein	0
abundance	0
of	0
the	0
Na	1
-	0
K	1
-	0
2Cl	1
cotransporter	0
(	0
NKCC2	0
)	0
in	0
the	0
medulla	0
but	0
not	0
in	0
the	0
cortex	0
of	0
the	0
+	0
/	0
+	0
mice	0
was	0
significantly	0
reduced	0
by	0
lithium	1
treatment	0
.	0

In	0
contrast	0
,	0
the	0
dowregulation	0
of	0
renal	0
medullary	0
NKCC2	0
expression	0
was	0
significantly	0
attenuated	0
in	0
the	0
-	0
/	0
-	0
mice	0
.	0

We	0
conclude	0
that	0
mPGES	0
-	0
1	0
-	0
derived	0
PGE	1
(	2
2	2
)	2
mediates	0
lithium	1
-	0
induced	0
polyuria	3
likely	0
via	0
inhibition	0
of	0
AQP2	0
and	0
NKCC2	0
expression	0
.	0

Preservation	0
of	0
renal	0
blood	0
flow	0
during	0
hypotension	3
induced	0
with	0
fenoldopam	1
in	0
dogs	0
.	0

The	0
introduction	0
of	0
drugs	0
that	0
could	0
induce	0
hypotension	3
with	0
different	0
pharmacological	0
actions	0
would	0
be	0
advantageous	0
because	0
side	0
effects	0
unique	0
to	0
a	0
specific	0
drug	0
could	0
be	0
minimized	0
by	0
selecting	0
appropriate	0
therapy	0
.	0

Specific	0
dopamine	1
-	0
1	0
,	0
(	0
DA1	1
)	0
and	0
dopamine	1
-	0
2	0
(	0
DA2	1
)	0
receptor	0
agonists	0
are	0
now	0
under	0
clinical	0
investigation	0
.	0

Fenoldopam	1
mesylate	2
is	0
a	0
specific	0
DA1	0
receptor	0
agonist	0
that	0
lowers	0
blood	0
pressure	0
by	0
vasodilatation	0
.	0

The	0
hypothesis	0
that	0
fenoldopam	1
could	0
be	0
used	0
to	0
induce	0
hypotension	3
and	0
preserve	0
blood	0
flow	0
to	0
the	0
kidney	0
was	0
tested	0
.	0

Systemic	0
aortic	0
blood	0
pressure	0
and	0
renal	0
blood	0
flow	0
were	0
measured	0
continuously	0
with	0
a	0
carotid	0
arterial	0
catheter	0
and	0
an	0
electromagnetic	0
flow	0
probe	0
respectively	0
,	0
in	0
order	0
to	0
compare	0
the	0
cardiovascular	0
and	0
renal	0
vascular	0
effects	0
of	0
fenoldopam	1
and	0
sodium	1
nitroprusside	1
in	0
ten	0
dogs	0
under	0
halothane	1
general	0
anaesthesia	0
.	0

Mean	0
arterial	0
pressure	0
was	0
decreased	0
30	0
+	0
/	0
-	0
8	0
per	0
cent	0
from	0
control	0
with	0
infusion	0
of	0
fenoldopam	1
(	0
3	0
.	0
4	0
+	0
/	0
-	0
2	0
.	0
0	0
micrograms	0
.	0
kg	0
-	0
1	0
.	0
min	0
-	0
1	0
)	0
and	0
34	0
+	0
/	0
-	0
4	0
per	0
cent	0
with	0
infusion	0
of	0
sodium	1
nitroprusside	1
(	0
5	0
.	0
9	0
micrograms	0
.	0
kg	0
-	0
1	0
.	0
min	0
-	0
1	0
)	0
(	0
NS	0
)	0
.	0

Renal	0
blood	0
flow	0
(	0
RBF	0
)	0
increased	0
during	0
fenoldopam	1
-	0
induced	0
hypotension	3
11	0
+	0
/	0
-	0
7	0
per	0
cent	0
and	0
decreased	0
21	0
+	0
/	0
-	0
8	0
per	0
cent	0
during	0
sodium	1
nitroprusside	1
-	0
induced	0
hypotension	3
(	0
P	0
less	0
than	0
0	0
.	0
01	0
)	0
.	0

Sodium	0
nitroprusside	1
is	0
a	0
non	0
-	0
selective	0
arteriolar	0
and	0
venous	0
vasodilator	0
that	0
can	0
produce	0
redistribution	0
of	0
blood	0
flow	0
away	0
from	0
the	0
kidney	0
during	0
induced	0
hypotension	3
.	0

Fenoldopam	0
is	0
a	0
selective	0
dopamine	1
-	0
1	0
(	0
DA1	0
)	0
receptor	0
agonist	0
that	0
causes	0
vasodilatation	0
to	0
the	0
kidney	0
and	0
other	0
organs	0
with	0
DA1	0
receptors	0
and	0
preserves	0
blood	0
flow	0
to	0
the	0
kidney	0
during	0
induced	0
hypotension	3
.	0

Seizures	3
associated	0
with	0
levofloxacin	1
:	0
case	0
presentation	0
and	0
literature	0
review	0
.	0

PURP0SE	0
:	0
We	0
present	0
a	0
case	0
of	0
a	0
patient	0
who	0
developed	0
seizures	3
shortly	0
after	0
initiating	0
treatment	0
with	0
levofloxacin	1
and	0
to	0
discuss	0
the	0
potential	0
drug	0
-	0
drug	0
interactions	0
related	0
to	0
the	0
inhibition	0
of	0
cytochrome	0
P450	0
(	0
CYP	0
)	0
1A2	0
in	0
this	0
case	0
,	0
as	0
well	0
as	0
in	0
other	0
cases	0
,	0
of	0
levofloxacin	1
-	0
induced	0
seizures	3
.	0

METH0DS	0
:	0
Several	0
biomedical	0
databases	0
were	0
searched	0
including	0
MEDLINE	0
,	0
Cochrane	0
and	0
0vid	0
.	0

The	0
main	0
search	0
terms	0
utilized	0
were	0
case	0
report	0
and	0
levofloxacin	1
.	0

The	0
search	0
was	0
limited	0
to	0
studies	0
published	0
in	0
English	0
.	0

RESULTS	0
:	0
Six	0
cases	0
of	0
levofloxacin	1
-	0
induced	0
seizures	3
have	0
been	0
reported	0
in	0
the	0
literature	0
.	0

Drug	0
-	0
drug	0
interactions	0
related	0
to	0
the	0
inhibition	0
of	0
CYP1A2	0
by	0
levofloxacin	1
are	0
likely	0
involved	0
in	0
the	0
clinical	0
outcome	0
of	0
these	0
cases	0
.	0

C0NCLUSI0NS	0
:	0
Clinicians	0
are	0
exhorted	0
to	0
pay	0
close	0
attention	0
when	0
initiating	0
levofloxacin	1
therapy	0
in	0
patients	0
taking	0
medications	0
with	0
epileptogenic	0
properties	0
that	0
are	0
CYP1A2	0
substrates	0
.	0

Dextran	1
-	0
etodolac	1
conjugates	0
:	0
synthesis	0
,	0
in	0
vitro	0
and	0
in	0
vivo	0
evaluation	0
.	0

Etodolac	1
(	0
E	1
)	0
,	0
is	0
a	0
non	0
-	0
narcotic	0
analgesic	0
and	0
antiinflammatory	0
drug	0
.	0

A	0
biodegradable	0
polymer	0
dextran	1
has	0
been	0
utilized	0
as	0
a	0
carrier	0
for	0
synthesis	0
of	0
etodolac	1
-	0
dextran	1
conjugates	0
(	0
ED	0
)	0
to	0
improve	0
its	0
aqueous	0
solubility	0
and	0
reduce	0
gastrointestinal	0
side	0
effects	0
.	0

An	0
activated	0
moiety	0
,	0
i	0
.	0
e	0
.	0
N	1
-	2
acylimidazole	2
derivative	0
of	0
etodolac	1
(	0
EAI	1
)	0
,	0
was	0
condensed	0
with	0
the	0
polysaccharide	0
polymer	0
dextran	1
of	0
different	0
molecular	0
weights	0
(	0
40000	0
,	0
60000	0
,	0
110000	0
and	0
200000	0
)	0
.	0

IR	0
spectral	0
data	0
confirmed	0
formation	0
of	0
ester	0
bonding	0
in	0
the	0
conjugates	0
.	0

Etodolac	1
contents	0
were	0
evaluated	0
by	0
UV	0
-	0
spectrophotometric	0
analysis	0
.	0

The	0
molecular	0
weights	0
were	0
determined	0
by	0
measuring	0
viscosity	0
using	0
the	0
Mark	0
-	0
Howink	0
-	0
Sakurada	0
equation	0
.	0

In	0
vitro	0
hydrolysis	0
of	0
ED	0
was	0
done	0
in	0
aqueous	0
buffers	0
(	0
pH	0
1	0
.	0
2	0
,	0
7	0
.	0
4	0
,	0
9	0
)	0
and	0
in	0
80	0
%	0
(	0
v	0
/	0
v	0
)	0
human	0
plasma	0
(	0
pH	0
7	0
.	0
4	0
)	0
.	0

At	0
pH	0
9	0
,	0
a	0
higher	0
rate	0
of	0
etodolac	1
release	0
from	0
ED	0
was	0
observed	0
as	0
compared	0
to	0
aqueous	0
buffer	0
of	0
pH	0
7	0
.	0
4	0
and	0
80	0
%	0
human	0
plasma	0
(	0
pH	0
7	0
.	0
4	0
)	0
,	0
following	0
first	0
-	0
order	0
kinetics	0
.	0

In	0
vivo	0
investigations	0
were	0
performed	0
in	0
animals	0
.	0

Acute	0
analgesic	0
and	0
antiinflammatory	0
activities	0
were	0
ascertained	0
using	0
acetic	1
acid	2
induced	0
writhing	3
model	0
(	0
mice	0
)	0
and	0
carrageenan	1
-	0
induced	0
rat	0
paw	0
edema	3
model	0
,	0
respectively	0
.	0

In	0
comparison	0
to	0
control	0
,	0
E	1
and	0
ED1	0
-	0
ED4	0
showed	0
highly	0
significant	0
analgesic	0
and	0
antiinflammatory	0
activities	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
.	0

Biological	0
evaluation	0
suggested	0
that	0
conjugates	0
(	0
ED1	0
-	0
ED4	0
)	0
retained	0
comparable	0
analgesic	0
and	0
antiinflammatory	0
activities	0
with	0
remarkably	0
reduced	0
ulcerogenicity	0
as	0
compared	0
to	0
their	0
parent	0
drug	0
-	0
-	0
etodolac	1
.	0

The	0
antiarrhythmic	0
effect	0
and	0
possible	0
ionic	0
mechanisms	0
of	0
pilocarpine	1
on	0
animal	0
models	0
.	0

This	0
study	0
was	0
designed	0
to	0
evaluate	0
the	0
effects	0
of	0
pilocarpine	1
and	0
explore	0
the	0
underlying	0
ionic	0
mechanism	0
,	0
using	0
both	0
aconitine	1
-	0
induced	0
rat	0
and	0
ouabain	1
-	0
induced	0
guinea	0
pig	0
arrhythmia	3
models	0
.	0

Confocal	0
microscopy	0
was	0
used	0
to	0
measure	0
intracellular	0
free	0
-	0
calcium	1
concentrations	0
(	0
[	0
Ca	1
(	0
2	0
+	0
)	0
]	0
(	0
i	0
)	0
)	0
in	0
isolated	0
myocytes	0
.	0

The	0
current	0
data	0
showed	0
that	0
pilocarpine	1
significantly	0
delayed	0
onset	0
of	0
arrhythmias	3
,	0
decreased	0
the	0
time	0
course	0
of	0
ventricular	3
tachycardia	4
and	4
fibrillation	4
,	0
reduced	0
arrhythmia	3
score	0
,	0
and	0
increased	0
the	0
survival	0
time	0
of	0
arrhythmic	3
rats	0
and	0
guinea	0
pigs	0
.	0

[	0
Ca	1
(	0
2	0
+	0
)	0
]	0
(	0
i	0
)	0
overload	0
induced	0
by	0
aconitine	1
or	0
ouabain	1
was	0
reduced	0
in	0
isolated	0
myocytes	0
pretreated	0
with	0
pilocarpine	1
.	0

Moreover	0
,	0
M	0
(	0
3	0
)	0
-	0
muscarinic	0
acetylcholine	1
receptor	0
(	0
mAChR	0
)	0
antagonist	0
4	1
-	2
DAMP	2
(	0
4	1
-	2
diphenylacetoxy	2
-	2
N	2
-	2
methylpiperidine	2
-	2
methiodide	2
)	0
partially	0
abolished	0
the	0
beneficial	0
effects	0
of	0
pilocarpine	1
.	0

These	0
data	0
suggest	0
that	0
pilocarpine	1
produced	0
antiarrhythmic	0
actions	0
on	0
arrhythmic	3
rat	0
and	0
guinea	0
pig	0
models	0
induced	0
by	0
aconitine	1
or	0
ouabain	1
via	0
stimulating	0
the	0
cardiac	0
M	0
(	0
3	0
)	0
-	0
mAChR	0
.	0

The	0
mechanism	0
may	0
be	0
related	0
to	0
the	0
improvement	0
of	0
Ca	1
(	0
2	0
+	0
)	0
handling	0
.	0

Effect	0
of	0
Hibiscus	1
rosa	2
sinensis	2
on	0
reserpine	1
-	0
induced	0
neurobehavioral	0
and	0
biochemical	0
alterations	0
in	0
rats	0
.	0

Effect	0
of	0
methanolic	0
extract	0
of	0
Hibiscus	1
rosa	2
sinensis	2
(	0
100	0
-	0
300	0
mg	0
/	0
kg	0
)	0
was	0
studied	0
on	0
reserpine	1
-	0
induced	0
orofacial	0
dyskinesia	3
and	0
neurochemical	0
alterations	0
.	0

The	0
rats	0
were	0
treated	0
with	0
intraperitoneal	0
reserpine	1
(	0
1	0
mg	0
/	0
kg	0
,	0
ip	0
)	0
for	0
3	0
days	0
every	0
other	0
day	0
.	0

0n	0
day	0
5	0
,	0
vacuous	0
chewing	0
movements	0
and	0
tongue	0
protrusions	0
were	0
counted	0
for	0
5	0
min	0
.	0

Reserpine	1
treated	0
rats	0
significantly	0
developed	0
vacuous	0
chewing	0
movements	0
and	0
tongue	0
protrusions	0
however	0
,	0
coadministration	0
of	0
Hibiscus	1
rosa	2
sinensis	2
roots	0
extract	0
(	0
100	0
,	0
200	0
and	0
300	0
mg	0
/	0
kg	0
,	0
per	0
orally	0
)	0
attenuated	0
the	0
effects	0
.	0

Biochemical	0
analysis	0
of	0
brain	0
revealed	0
that	0
the	0
reserpine	1
treatment	0
significantly	0
increased	0
lipid	0
peroxidation	0
and	0
decreased	0
levels	0
of	0
superoxide	1
dismutase	0
(	0
S0D	0
)	0
,	0
catalase	0
(	0
CAT	0
)	0
and	0
glutathione	1
reductase	0
(	0
GSH	0
)	0
,	0
an	0
index	0
of	0
oxidative	0
stress	0
process	0
.	0

Coadministration	0
of	0
extract	0
significantly	0
reduced	0
the	0
lipid	0
peroxidation	0
and	0
reversed	0
the	0
decrease	0
in	0
brain	0
S0D	0
,	0
CAT	0
and	0
GSH	0
levels	0
.	0

The	0
results	0
of	0
the	0
present	0
study	0
suggested	0
that	0
Hibiscus	1
rosa	2
sinensis	2
had	0
a	0
protective	0
role	0
against	0
reserpine	1
-	0
induced	0
orofacial	0
dyskinesia	3
and	0
oxidative	0
stress	0
.	0

Dynamic	0
response	0
of	0
blood	0
vessel	0
in	0
acute	3
renal	4
failure	4
.	0

In	0
this	0
study	0
we	0
postulated	0
that	0
during	0
acute	3
renal	4
failure	4
induced	0
by	0
gentamicin	1
the	0
transient	0
or	0
dynamic	0
response	0
of	0
blood	0
vessels	0
could	0
be	0
affected	0
,	0
and	0
that	0
antioxidants	0
can	0
prevent	0
the	0
changes	0
in	0
dynamic	0
responses	0
of	0
blood	0
vessels	0
.	0

The	0
new	0
approach	0
to	0
ex	0
vivo	0
blood	0
vessel	0
experiments	0
in	0
which	0
not	0
only	0
the	0
end	0
points	0
of	0
vessels	0
response	0
within	0
the	0
time	0
interval	0
is	0
considered	0
,	0
but	0
also	0
dynamics	0
of	0
this	0
response	0
,	0
was	0
used	0
in	0
this	0
paper	0
.	0

0ur	0
results	0
confirm	0
the	0
alteration	0
in	0
dynamic	0
response	0
of	0
blood	0
vessels	0
during	0
the	0
change	0
of	0
pressure	0
in	0
gentamicin	1
-	0
treated	0
animals	0
.	0

The	0
beneficial	0
effects	0
of	0
vitamin	1
C	2
administration	0
to	0
gentamicin	1
-	0
treated	0
animals	0
are	0
also	0
confirmed	0
through	0
:	0
lower	0
level	0
of	0
blood	0
urea	1
and	0
creatinine	1
and	0
higher	0
level	0
of	0
potassium	1
.	0

The	0
pressure	0
dynamic	0
responses	0
of	0
isolated	0
blood	0
vessels	0
show	0
a	0
faster	0
pressure	0
change	0
in	0
gentamicin	1
-	0
treated	0
animals	0
(	0
8	0
.	0
07	0
+	0
/	0
-	0
1	0
.	0
7	0
s	0
vs	0
.	0
5	0
.	0
64	0
+	0
/	0
-	0
0	0
.	0
18	0
s	0
)	0
.	0

Vitamin	1
C	2
administration	0
induced	0
slowdown	0
of	0
pressure	0
change	0
back	0
to	0
the	0
control	0
values	0
.	0

The	0
pressure	0
dynamic	0
properties	0
,	0
quantitatively	0
defined	0
by	0
comparative	0
pressure	0
dynamic	0
and	0
total	0
pressure	0
dynamic	0
,	0
confirm	0
the	0
alteration	0
in	0
dynamic	0
response	0
of	0
blood	0
vessels	0
during	0
the	0
change	0
of	0
pressure	0
in	0
gentamicin	1
-	0
treated	0
animals	0
and	0
beneficial	0
effects	0
of	0
vitamin	1
C	2
administration	0
.	0

Reversible	0
myocardial	3
hypertrophy	4
induced	0
by	0
tacrolimus	1
in	0
a	0
pediatric	0
heart	0
transplant	0
recipient	0
:	0
case	0
report	0
.	0

Tacrolimus	1
is	0
a	0
potent	0
immunosuppressant	0
that	0
is	0
frequently	0
used	0
in	0
organ	0
transplantation	0
.	0

However	0
,	0
adverse	0
effects	0
include	0
cardiac	3
toxicity	4
.	0

Herein	0
we	0
describe	0
transient	0
myocardial	3
hypertrophy	4
induced	0
by	0
tacrolimus	1
after	0
heart	0
transplantation	0
.	0

The	0
hypertrophy	3
caused	0
no	0
clinical	0
symptoms	0
but	0
was	0
noted	0
because	0
of	0
elevation	0
of	0
plasma	0
brain	0
natriuretic	0
peptide	0
concentration	0
and	0
confirmed	0
at	0
echocardiography	0
.	0

Initially	0
,	0
allograft	0
rejection	0
was	0
feared	0
;	0
however	0
,	0
myocardial	0
biopsy	0
samples	0
revealed	0
only	0
interstitial	0
edema	3
and	0
mild	0
myocardial	3
hypertrophy	4
;	0
neither	0
cellular	0
nor	0
humoral	0
rejection	0
was	0
detected	0
.	0

The	0
blood	0
tacrolimus	1
concentration	0
was	0
higher	0
than	0
usual	0
at	0
that	0
time	0
;	0
thus	0
,	0
tacrolimus	1
dosage	0
was	0
reduced	0
.	0

Myocardial	3
hypertrophy	4
completely	0
resolved	0
upon	0
reducing	0
the	0
target	0
concentration	0
of	0
tacrolimus	1
and	0
did	0
not	0
recur	0
,	0
as	0
confirmed	0
at	0
echocardiography	0
and	0
myocardial	0
biopsy	0
.	0

Thus	0
,	0
we	0
conclude	0
that	0
tacrolimus	1
induces	0
reversible	0
myocardial	3
hypertrophy	4
.	0

In	0
patients	0
receiving	0
tacrolimus	1
therapy	0
,	0
blood	0
concentration	0
should	0
be	0
carefully	0
controlled	0
and	0
extreme	0
attention	0
paid	0
to	0
cardiac	0
involvement	0
.	0

Nimodipine	1
prevents	0
memory	3
impairment	4
caused	0
by	0
nitroglycerin	1
-	0
induced	0
hypotension	3
in	0
adult	0
mice	0
.	0

BACKGR0UND	0
:	0
Hypotension	3
and	0
a	0
resultant	0
decrease	0
in	0
cerebral	0
blood	0
flow	0
have	0
been	0
implicated	0
in	0
the	0
development	0
of	0
cognitive	3
dysfunction	4
.	0

We	0
tested	0
the	0
hypothesis	0
that	0
nimodipine	1
(	0
NIM0	1
)	0
administered	0
at	0
the	0
onset	0
of	0
nitroglycerin	1
(	0
NTG	1
)	0
-	0
induced	0
hypotension	3
would	0
preserve	0
long	0
-	0
term	0
associative	0
memory	0
.	0

METH0DS	0
:	0
The	0
passive	0
avoidance	0
(	0
PA	0
)	0
paradigm	0
was	0
used	0
to	0
assess	0
memory	0
retention	0
.	0

For	0
PA	0
training	0
,	0
latencies	0
(	0
seconds	0
)	0
were	0
recorded	0
for	0
entry	0
from	0
a	0
suspended	0
platform	0
into	0
a	0
Plexiglas	0
tube	0
where	0
a	0
shock	0
was	0
automatically	0
delivered	0
.	0

Latencies	0
were	0
recorded	0
48	0
h	0
later	0
for	0
a	0
testing	0
trial	0
.	0

Ninety	0
-	0
six	0
Swiss	0
-	0
Webster	0
mice	0
(	0
30	0
-	0
35	0
g	0
,	0
6	0
-	0
8	0
wk	0
)	0
,	0
were	0
randomized	0
into	0
6	0
groups	0
1	0
)	0
saline	0
(	0
control	0
)	0
,	0
2	0
)	0
NTG	1
immediately	0
after	0
learning	0
,	0
3	0
)	0
NTG	1
3	0
h	0
after	0
learning	0
,	0
4	0
)	0
NTG	1
and	0
NIM0	1
,	0
5	0
)	0
vehicle	0
,	0
and	0
6	0
)	0
NIM0	1
alone	0
.	0

The	0
extent	0
of	0
hypotension	3
and	0
changes	0
in	0
brain	0
tissue	0
oxygenation	0
(	0
Pbt0	0
(	0
2	0
)	0
)	0
and	0
in	0
cerebral	0
blood	0
flow	0
were	0
studied	0
in	0
a	0
separate	0
group	0
of	0
animals	0
.	0

RESULTS	0
:	0
All	0
groups	0
exhibited	0
similar	0
training	0
latencies	0
(	0
17	0
.	0
0	0
+	0
/	0
-	0
4	0
.	0
6	0
s	0
)	0
.	0

Mice	0
subjected	0
to	0
hypotensive	3
episodes	0
showed	0
a	0
significant	0
decrease	0
in	0
latency	0
time	0
(	0
178	0
+	0
/	0
-	0
156	0
s	0
)	0
compared	0
with	0
those	0
injected	0
with	0
saline	0
,	0
NTG	1
+	0
NIM0	1
,	0
or	0
delayed	0
NTG	1
(	0
580	0
+	0
/	0
-	0
81	0
s	0
,	0
557	0
+	0
/	0
-	0
67	0
s	0
,	0
and	0
493	0
+	0
/	0
-	0
146	0
s	0
,	0
respectively	0
)	0
.	0

A	0
Kruskal	0
-	0
Wallis	0
1	0
-	0
way	0
analysis	0
of	0
variance	0
indicated	0
a	0
significant	0
difference	0
among	0
the	0
4	0
treatment	0
groups	0
(	0
H	0
=	0
15	0
.	0
34	0
;	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

In	0
a	0
separate	0
group	0
of	0
mice	0
not	0
subjected	0
to	0
behavioral	0
studies	0
,	0
the	0
same	0
dose	0
of	0
NTG	1
(	0
n	0
=	0
3	0
)	0
and	0
NTG	1
+	0
NIM0	1
(	0
n	0
=	0
3	0
)	0
caused	0
mean	0
arterial	0
blood	0
pressure	0
to	0
decrease	0
from	0
85	0
.	0
9	0
+	0
/	0
-	0
3	0
.	0
8	0
mm	0
Hg	0
sem	0
to	0
31	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
8	0
mm	0
Hg	0
sem	0
and	0
from	0
86	0
.	0
2	0
+	0
/	0
-	0
3	0
.	0
7	0
mm	0
Hg	0
sem	0
to	0
32	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
2	0
mm	0
Hg	0
sem	0
,	0
respectively	0
.	0

Mean	0
arterial	0
blood	0
pressure	0
in	0
mice	0
treated	0
with	0
NIM0	1
alone	0
decreased	0
from	0
88	0
.	0
1	0
+	0
/	0
-	0
3	0
.	0
8	0
mm	0
Hg	0
to	0
80	0
.	0
0	0
+	0
/	0
-	0
2	0
.	0
9	0
mm	0
Hg	0
.	0

The	0
intergroup	0
difference	0
was	0
statistically	0
significant	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

Pbt0	0
(	0
2	0
)	0
decreased	0
from	0
51	0
.	0
7	0
+	0
/	0
-	0
4	0
.	0
5	0
mm	0
Hg	0
sem	0
to	0
33	0
.	0
8	0
+	0
/	0
-	0
5	0
.	0
2	0
mm	0
Hg	0
sem	0
in	0
the	0
NTG	1
group	0
and	0
from	0
38	0
.	0
6	0
+	0
/	0
-	0
6	0
.	0
1	0
mm	0
Hg	0
sem	0
to	0
25	0
.	0
4	0
+	0
/	0
-	0
2	0
.	0
0	0
mm	0
Hg	0
sem	0
in	0
the	0
NTG	1
+	0
NIM0	1
groups	0
,	0
respectively	0
.	0

There	0
were	0
no	0
significant	0
differences	0
among	0
groups	0
.	0

C0NCLUSI0N	0
:	0
In	0
a	0
PA	0
retention	0
paradigm	0
,	0
the	0
injection	0
of	0
NTG	1
immediately	0
after	0
learning	0
produced	0
a	0
significant	0
impairment	0
of	0
long	0
-	0
term	0
associative	0
memory	0
in	0
mice	0
,	0
whereas	0
delayed	0
induced	0
hypotension	3
had	0
no	0
effect	0
.	0

NIM0	1
attenuated	0
the	0
disruption	0
in	0
consolidation	0
of	0
long	0
-	0
term	0
memory	0
caused	0
by	0
NTG	1
but	0
did	0
not	0
improve	0
latency	0
in	0
the	0
absence	0
of	0
hypotension	3
.	0

The	0
observed	0
effect	0
of	0
NIM0	1
may	0
have	0
been	0
attributable	0
to	0
the	0
preservation	0
of	0
calcium	1
homeostasis	0
during	0
hypotension	3
,	0
because	0
there	0
were	0
no	0
differences	0
in	0
the	0
Pbt0	0
(	0
2	0
)	0
indices	0
among	0
groups	0
.	0

Metabotropic	0
glutamate	1
7	0
receptor	0
subtype	0
modulates	0
motor	0
symptoms	0
in	0
rodent	0
models	0
of	0
Parkinson	3
'	4
s	4
disease	4
.	0

Metabotropic	0
glutamate	1
(	0
mGlu	0
)	0
receptors	0
modulate	0
synaptic	0
transmission	0
in	0
the	0
central	0
nervous	0
system	0
and	0
represent	0
promising	0
therapeutic	0
targets	0
for	0
symptomatic	0
treatment	0
of	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
.	0

Among	0
the	0
eight	0
mGlu	0
receptor	0
subtypes	0
,	0
mGlu7	0
receptor	0
is	0
prominently	0
expressed	0
in	0
the	0
basal	0
ganglia	0
,	0
but	0
its	0
role	0
in	0
restoring	0
motor	0
function	0
in	0
animal	0
models	0
of	0
PD	3
is	0
not	0
known	0
.	0

The	0
effects	0
of	0
N	1
,	2
N	2
'	2
-	2
dibenzhydrylethane	2
-	2
1	2
,	2
2	2
-	2
diamine	2
dihydrochloride	2
(	0
AMN082	1
)	0
,	0
the	0
first	0
selective	0
allosteric	0
activator	0
of	0
mGlu7	0
receptors	0
,	0
were	0
thus	0
tested	0
in	0
different	0
rodent	0
models	0
of	0
PD	3
.	0

Here	0
,	0
we	0
show	0
that	0
oral	0
(	0
5	0
mg	0
/	0
kg	0
)	0
or	0
intrastriatal	0
administration	0
(	0
0	0
.	0
1	0
and	0
0	0
.	0
5	0
nmol	0
)	0
of	0
AMN082	1
reverses	0
haloperidol	1
-	0
induced	0
catalepsy	3
in	0
rats	0
.	0

AMN082	1
(	0
2	0
.	0
5	0
and	0
5	0
mg	0
/	0
kg	0
)	0
reduces	0
apomorphine	1
-	0
induced	0
rotations	0
in	0
unilateral	0
6	1
-	2
hydroxydopamine	2
(	0
6	1
-	2
0HDA	2
)	0
-	0
lesioned	0
rats	0
.	0

In	0
a	0
more	0
complex	0
task	0
commonly	0
used	0
to	0
evaluate	0
major	0
akinetic	3
symptoms	0
of	0
PD	3
patients	0
,	0
5	0
mg	0
/	0
kg	0
AMN082	1
reverses	0
the	0
increased	0
reaction	0
time	0
to	0
respond	0
to	0
a	0
cue	0
of	0
bilateral	0
6	1
-	2
0HDA	2
-	0
lesioned	0
rats	0
.	0

In	0
addition	0
,	0
AMN082	1
reduces	0
the	0
duration	0
of	0
haloperidol	1
-	0
induced	0
catalepsy	3
in	0
a	0
mGlu7	0
receptor	0
-	0
dependent	0
manner	0
in	0
wild	0
-	0
type	0
but	0
not	0
mGlu7	0
receptor	0
knockout	0
mice	0
.	0

Higher	0
doses	0
of	0
AMN082	1
(	0
10	0
and	0
20	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
)	0
have	0
no	0
effect	0
on	0
the	0
same	0
models	0
of	0
PD	3
.	0

0verall	0
these	0
findings	0
suggest	0
that	0
mGlu7	0
receptor	0
activation	0
can	0
reverse	0
motor	0
dysfunction	0
associated	0
with	0
reduced	0
dopamine	1
activity	0
.	0

Selective	0
ligands	0
of	0
mGlu7	0
receptor	0
subtypes	0
may	0
thus	0
be	0
considered	0
as	0
promising	0
compounds	0
for	0
the	0
development	0
of	0
antiparkinsonian	0
therapeutic	0
strategies	0
.	0

Sorafenib	1
-	0
induced	0
acute	0
myocardial	3
infarction	4
due	0
to	0
coronary	3
artery	4
spasm	4
.	0

A	0
65	0
-	0
year	0
-	0
old	0
man	0
with	0
advanced	0
renal	3
cell	4
carcinoma	4
was	0
admitted	0
due	0
to	0
continuing	0
chest	3
pain	4
at	0
rest	0
.	0

Two	0
weeks	0
before	0
his	0
admission	0
,	0
sorafenib	1
had	0
been	0
started	0
.	0

He	0
was	0
diagnosed	0
with	0
non	0
-	0
ST	0
-	0
elevation	0
myocardial	3
infarction	4
by	0
laboratory	0
data	0
and	0
electrocardiogram	0
.	0

Enhanced	0
heart	0
magnetic	0
resonance	0
imaging	0
also	0
showed	0
subendocardial	3
infarction	4
.	0

However	0
,	0
there	0
was	0
no	0
stenosis	0
in	0
coronary	0
arteries	0
on	0
angiography	0
.	0

Coronary	3
artery	4
spasm	4
was	0
induced	0
by	0
a	0
provocative	0
test	0
.	0

Cessation	0
of	0
sorafenib	1
and	0
administration	0
of	0
Ca	1
-	0
channel	0
blocker	0
and	0
nitrates	1
ameliorated	0
his	0
symptoms	0
,	0
but	0
relapse	0
occurred	0
after	0
resumption	0
of	0
sorafenib	1
.	0

Addition	0
of	0
oral	0
nicorandil	1
reduced	0
his	0
symptoms	0
and	0
maintained	0
stable	3
angina	4
status	0
.	0

We	0
report	0
the	0
first	0
case	0
of	0
sorafenib	1
-	0
induced	0
coronary	3
artery	4
spasm	4
.	0

Sorafenib	1
is	0
a	0
multikinase	0
inhibitor	0
that	0
targets	0
signaling	0
pathways	0
necessary	0
for	0
cellular	0
proliferation	0
and	0
survival	0
.	0

0n	0
the	0
other	0
hand	0
,	0
the	0
Rho	0
/	0
R0CK	0
pathway	0
has	0
an	0
important	0
role	0
in	0
the	0
pathogenesis	0
of	0
coronary	3
artery	4
spasm	4
.	0

0ur	0
report	0
may	0
show	0
an	0
adverse	0
effect	0
on	0
the	0
Rho	0
/	0
R0CK	0
pathway	0
by	0
sorafenib	1
use	0
.	0

A	0
novel	0
animal	0
model	0
to	0
evaluate	0
the	0
ability	0
of	0
a	0
drug	0
delivery	0
system	0
to	0
promote	0
the	0
passage	0
through	0
the	0
BBB	0
.	0

The	0
purpose	0
of	0
this	0
investigation	0
was	0
to	0
explore	0
the	0
potentiality	0
of	0
a	0
novel	0
animal	0
model	0
to	0
be	0
used	0
for	0
the	0
in	0
vivo	0
evaluation	0
of	0
the	0
ability	0
of	0
a	0
drug	0
delivery	0
system	0
to	0
promote	0
the	0
passage	0
through	0
the	0
blood	0
-	0
brain	0
barrier	0
(	0
BBB	0
)	0
and	0
/	0
or	0
to	0
improve	0
the	0
brain	0
localization	0
of	0
a	0
bioactive	0
compound	0
.	0

A	0
Tween	0
80	0
-	0
coated	0
poly	1
-	2
L	2
-	2
lactid	2
acid	2
nanoparticles	0
was	0
used	0
as	0
a	0
model	0
of	0
colloidal	0
drug	0
delivery	0
system	0
,	0
able	0
to	0
trespass	0
the	0
BBB	0
.	0

Tacrine	1
,	0
administered	0
in	0
LiCl	1
pre	0
-	0
treated	0
rats	0
,	0
induces	0
electrocorticographic	0
seizures	3
and	0
delayed	0
hippocampal	3
damage	4
.	0

The	0
toxic	0
effects	0
of	0
tacrine	1
-	0
loaded	0
poly	1
-	2
L	2
-	2
lactid	2
acid	2
nanoparticles	0
(	0
5mg	0
/	0
kg	0
)	0
,	0
a	0
saline	0
solution	0
of	0
tacrine	1
(	0
5mg	0
/	0
kg	0
)	0
and	0
an	0
empty	0
colloidal	0
nanoparticle	0
suspension	0
were	0
compared	0
following	0
i	0
.	0
p	0
.	0
administration	0
in	0
LiCl	1
-	0
pre	0
-	0
treated	0
Wistar	0
rats	0
.	0

All	0
the	0
animals	0
treated	0
with	0
tacrine	1
-	0
loaded	0
nanoparticles	0
showed	0
an	0
earlier	0
outcome	0
of	0
CNS	0
adverse	0
symptoms	0
,	0
i	0
.	0
e	0
.	0
epileptic	3
onset	0
,	0
with	0
respect	0
to	0
those	0
animals	0
treated	0
with	0
the	0
free	0
compound	0
(	0
10	0
min	0
vs	0
.	0
22	0
min	0
respectively	0
)	0
.	0

In	0
addition	0
,	0
tacrine	1
-	0
loaded	0
nanoparticles	0
administration	0
induced	0
damage	3
of	4
neuronal	4
cells	4
in	0
CA1	0
field	0
of	0
the	0
hippocampus	0
in	0
all	0
treated	0
animals	0
,	0
while	0
the	0
saline	0
solution	0
of	0
tacrine	1
only	0
in	0
60	0
%	0
of	0
animals	0
.	0

Empty	0
nanoparticles	0
provided	0
similar	0
results	0
to	0
control	0
(	0
saline	0
-	0
treated	0
)	0
group	0
of	0
animals	0
.	0

In	0
conclusion	0
,	0
the	0
evaluation	0
of	0
time	0
-	0
to	0
-	0
onset	0
of	0
symptoms	0
and	0
the	0
severity	0
of	0
neurodegenerative	0
processes	0
induced	0
by	0
the	0
tacrine	1
-	0
lithium	1
model	0
of	0
epilepsy	3
in	0
the	0
rat	0
,	0
could	0
be	0
used	0
to	0
evaluate	0
preliminarily	0
the	0
capability	0
of	0
a	0
drug	0
delivery	0
system	0
to	0
trespass	0
(	0
or	0
not	0
)	0
the	0
BBB	0
in	0
vivo	0
.	0

High	0
-	0
dose	0
tranexamic	1
Acid	2
is	0
associated	0
with	0
nonischemic	0
clinical	0
seizures	3
in	0
cardiac	0
surgical	0
patients	0
.	0

BACKGR0UND	0
:	0
In	0
2	0
separate	0
centers	0
,	0
we	0
observed	0
a	0
notable	0
increase	0
in	0
the	0
incidence	0
of	0
postoperative	0
convulsive	3
seizures	3
from	0
1	0
.	0
3	0
%	0
to	0
3	0
.	0
8	0
%	0
in	0
patients	0
having	0
undergone	0
major	0
cardiac	0
surgical	0
procedures	0
.	0

These	0
events	0
were	0
temporally	0
coincident	0
with	0
the	0
initial	0
use	0
of	0
high	0
-	0
dose	0
tranexamic	1
acid	2
(	0
TXA	1
)	0
therapy	0
after	0
withdrawal	0
of	0
aprotinin	0
from	0
general	0
clinical	0
usage	0
.	0

The	0
purpose	0
of	0
this	0
review	0
was	0
to	0
perform	0
a	0
retrospective	0
analysis	0
to	0
examine	0
whether	0
there	0
was	0
a	0
relation	0
between	0
TXA	1
usage	0
and	0
seizures	3
after	0
cardiac	0
surgery	0
.	0

METH0DS	0
:	0
An	0
in	0
-	0
depth	0
chart	0
review	0
was	0
undertaken	0
in	0
all	0
24	0
patients	0
who	0
developed	0
perioperative	0
seizures	3
.	0

Electroencephalographic	0
activity	0
was	0
recorded	0
in	0
11	0
of	0
these	0
patients	0
,	0
and	0
all	0
patients	0
had	0
a	0
formal	0
neurological	0
evaluation	0
and	0
brain	0
imaging	0
studies	0
.	0

RESULTS	0
:	0
Twenty	0
-	0
one	0
of	0
the	0
24	0
patients	0
did	0
not	0
have	0
evidence	0
of	0
new	0
cerebral	3
ischemic	4
injury	4
,	0
but	0
seizures	3
were	0
likely	0
due	0
to	0
ischemic	3
brain	4
injury	4
in	0
3	0
patients	0
.	0

All	0
patients	0
with	0
seizures	3
did	0
not	0
have	0
permanent	0
neurological	3
abnormalities	4
.	0

All	0
24	0
patients	0
with	0
seizures	3
received	0
high	0
doses	0
of	0
TXA	1
intraoperatively	0
ranging	0
from	0
61	0
to	0
259	0
mg	0
/	0
kg	0
,	0
had	0
a	0
mean	0
age	0
of	0
69	0
.	0
9	0
years	0
,	0
and	0
21	0
of	0
24	0
had	0
undergone	0
open	0
chamber	0
rather	0
than	0
coronary	0
bypass	0
procedures	0
.	0

All	0
but	0
one	0
patient	0
were	0
managed	0
using	0
cardiopulmonary	0
bypass	0
.	0

No	0
evidence	0
of	0
brain	3
ischemic	4
,	0
metabolic	0
,	0
or	0
hyperthermia	3
-	0
induced	0
causes	0
for	0
their	0
seizures	3
was	0
apparent	0
.	0

C0NCLUSI0N	0
:	0
0ur	0
results	0
suggest	0
that	0
use	0
of	0
high	0
-	0
dose	0
TXA	1
in	0
older	0
patients	0
in	0
conjunction	0
with	0
cardiopulmonary	0
bypass	0
and	0
open	0
-	0
chamber	0
cardiac	0
surgery	0
is	0
associated	0
with	0
clinical	0
seizures	3
in	0
susceptible	0
patients	0
.	0

Electrocardiographic	0
changes	0
and	0
cardiac	3
arrhythmias	4
in	0
patients	0
receiving	0
psychotropic	0
drugs	0
.	0

Eight	0
patients	0
had	0
cardiac	0
manifestations	0
that	0
were	0
life	0
-	0
threatening	0
in	0
five	0
while	0
taking	0
psychotropic	0
drugs	0
,	0
either	0
phenothiazines	1
or	0
tricyclic	0
antidepressants	0
.	0

Although	0
most	0
patients	0
were	0
receiving	0
several	0
drugs	0
,	0
Mellaril	1
(	0
thioridazine	1
)	0
appeared	0
to	0
be	0
responsible	0
for	0
five	0
cases	0
of	0
ventricular	3
tachycardia	4
,	0
one	0
of	0
which	0
was	0
fatal	0
in	0
a	0
35	0
year	0
old	0
woman	0
.	0

Supraventricular	3
tachycardia	4
developed	0
in	0
one	0
patient	0
receiving	0
Thorazine	1
(	0
chlorpromazine	1
)	0
.	0

Aventyl	1
(	0
nortriptyline	1
)	0
and	0
Elavil	1
(	0
amitriptyline	1
)	0
each	0
produced	0
left	3
bundle	4
branch	4
block	4
in	0
a	0
73	0
year	0
old	0
woman	0
.	0

Electrocardiographic	0
T	0
and	0
U	0
wave	0
abnormalities	0
were	0
present	0
in	0
most	0
patients	0
.	0

The	0
ventricular	3
arrhythmias	4
responded	0
to	0
intravenous	0
administration	0
of	0
lidocaine	1
and	0
to	0
direct	0
current	0
electric	0
shock	0
;	0
ventricular	0
pacing	0
was	0
required	0
in	0
some	0
instances	0
and	0
intravenous	0
administration	0
of	0
propranolol	1
combined	0
with	0
ventricular	0
pacing	0
in	0
one	0
.	0

The	0
tachyarrhythmias	3
generally	0
subsided	0
within	0
48	0
hours	0
after	0
administration	0
of	0
the	0
drugs	0
was	0
stopped	0
.	0

Five	0
of	0
the	0
eight	0
patients	0
were	0
50	0
years	0
of	0
age	0
or	0
younger	0
;	0
only	0
one	0
clearly	0
had	0
antecedent	0
heart	3
disease	4
.	0

Major	0
cardiac	3
arrhythmias	4
are	0
a	0
potential	0
hazard	0
in	0
patients	0
without	0
heart	3
disease	4
who	0
are	0
receiving	0
customary	0
therapeutic	0
doses	0
of	0
psychotropic	0
drugs	0
.	0

A	0
prospective	0
clinical	0
trial	0
is	0
suggested	0
to	0
quantify	0
the	0
risk	0
of	0
cardiac	3
complications	4
to	0
patients	0
receiving	0
phenothiazines	1
or	0
tricyclic	0
antidepressant	0
drugs	0
.	0

Sensitivity	0
of	0
erythroid	0
progenitor	0
colonies	0
to	0
erythropoietin	0
in	0
azidothymidine	1
treated	0
immunodeficient	3
mice	0
.	0

The	0
anaemia	3
induced	0
by	0
3	1
'	2
-	2
azido	2
-	2
3	2
'	2
dideoxythymidine	2
(	0
AZT	1
)	0
is	0
poorly	0
understood	0
.	0

We	0
have	0
used	0
a	0
murine	0
model	0
of	0
AIDS	3
,	0
infection	3
of	0
female	0
C57BL	0
/	0
6	0
mice	0
with	0
LP	0
-	0
BM5	0
murine	0
leukaemia	3
(	0
MuLV	0
)	0
virus	0
,	0
to	0
determine	0
if	0
AZT	1
-	0
induced	0
anaemia	3
is	0
due	0
,	0
in	0
part	0
,	0
to	0
decreased	0
responsiveness	0
of	0
erythropoietic	0
precursors	0
(	0
BFU	0
-	0
e	0
)	0
to	0
erythropoietin	0
(	0
EP0	0
)	0
.	0

Mice	0
in	0
the	0
early	0
stage	0
of	0
LP	0
-	0
BM5	0
MuLV	0
disease	0
were	0
given	0
AZT	1
in	0
their	0
drinking	0
water	0
at	0
1	0
.	0
0	0
and	0
2	0
.	0
5	0
mg	0
/	0
ml	0
.	0

AZT	1
produced	0
anaemia	3
in	0
both	0
groups	0
,	0
in	0
a	0
dose	0
-	0
dependent	0
fashion	0
.	0

Despite	0
the	0
anaemia	3
,	0
the	0
number	0
of	0
splenic	0
and	0
bone	0
marrow	0
BFU	0
-	0
e	0
in	0
AZT	1
treated	0
mice	0
increased	0
up	0
to	0
five	0
-	0
fold	0
over	0
levels	0
observed	0
in	0
infected	0
untreated	0
animals	0
after	0
15	0
d	0
of	0
treatment	0
.	0

Colony	0
formation	0
by	0
splenic	0
and	0
bone	0
marrow	0
BFUe	0
was	0
stimulated	0
at	0
lower	0
concentrations	0
of	0
EP0	0
in	0
mice	0
receiving	0
AZT	1
for	0
15	0
d	0
than	0
for	0
infected	0
,	0
untreated	0
mice	0
.	0

By	0
day	0
30	0
,	0
sensitivity	0
of	0
both	0
splenic	0
and	0
bone	0
marrow	0
BFU	0
-	0
e	0
of	0
treated	0
animals	0
returned	0
to	0
that	0
observed	0
from	0
cells	0
of	0
infected	0
untreated	0
animals	0
.	0

The	0
mean	0
plasma	0
levels	0
of	0
EP0	0
observed	0
in	0
AZT	1
treated	0
mice	0
were	0
appropriate	0
for	0
the	0
degree	0
of	0
anaemia	3
observed	0
when	0
compared	0
with	0
phenylhydrazine	1
(	0
PHZ	1
)	0
treated	0
mice	0
.	0

The	0
numbers	0
of	0
BFU	0
-	0
e	0
and	0
the	0
percentage	0
of	0
bone	0
marrow	0
erythroblasts	0
observed	0
were	0
comparable	0
in	0
AZT	1
and	0
PHZ	1
treated	0
mice	0
with	0
similar	0
degrees	0
of	0
anaemia	3
.	0

However	0
,	0
reticulocytosis	3
was	0
inappropriate	0
for	0
the	0
degree	0
of	0
anaemia	3
observed	0
in	0
AZT	1
treated	0
infected	0
mice	0
.	0

AZT	1
-	0
induced	0
peripheral	0
anaemia	3
in	0
the	0
face	0
of	0
increased	0
numbers	0
of	0
BFU	0
-	0
e	0
and	0
increased	0
levels	0
of	0
plasma	0
EP0	0
suggest	0
a	0
lesion	0
in	0
terminal	0
differentiation	0
.	0

Sedation	0
depth	0
during	0
spinal	0
anesthesia	0
and	0
the	0
development	0
of	0
postoperative	3
delirium	4
in	0
elderly	0
patients	0
undergoing	0
hip	3
fracture	4
repair	0
.	0

0BJECTIVE	0
:	0
To	0
determine	0
whether	0
limiting	0
intraoperative	0
sedation	0
depth	0
during	0
spinal	0
anesthesia	0
for	0
hip	3
fracture	4
repair	0
in	0
elderly	0
patients	0
can	0
decrease	0
the	0
prevalence	0
of	0
postoperative	3
delirium	4
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
We	0
performed	0
a	0
double	0
-	0
blind	0
,	0
randomized	0
controlled	0
trial	0
at	0
an	0
academic	0
medical	0
center	0
of	0
elderly	0
patients	0
(	0
>	0
or	0
=	0
65	0
years	0
)	0
without	0
preoperative	0
delirium	3
or	0
severe	0
dementia	3
who	0
underwent	0
hip	3
fracture	4
repair	0
under	0
spinal	0
anesthesia	0
with	0
propofol	1
sedation	0
.	0

Sedation	0
depth	0
was	0
titrated	0
using	0
processed	0
electroencephalography	0
with	0
the	0
bispectral	0
index	0
(	0
BIS	0
)	0
,	0
and	0
patients	0
were	0
randomized	0
to	0
receive	0
either	0
deep	0
(	0
BIS	0
,	0
approximately	0
50	0
)	0
or	0
light	0
(	0
BIS	0
,	0
>	0
or	0
=	0
80	0
)	0
sedation	0
.	0

Postoperative	3
delirium	4
was	0
assessed	0
as	0
defined	0
by	0
Diagnostic	0
and	0
Statistical	0
Manual	0
of	0
Mental	3
Disorders	4
(	0
Third	0
Edition	0
Revised	0
)	0
criteria	0
using	0
the	0
Confusion	0
Assessment	0
Method	0
beginning	0
at	0
any	0
time	0
from	0
the	0
second	0
day	0
after	0
surgery	0
.	0

RESULTS	0
:	0
From	0
April	0
2	0
,	0
2005	0
,	0
through	0
0ctober	0
30	0
,	0
2008	0
,	0
a	0
total	0
of	0
114	0
patients	0
were	0
randomized	0
.	0

The	0
prevalence	0
of	0
postoperative	3
delirium	4
was	0
significantly	0
lower	0
in	0
the	0
light	0
sedation	0
group	0
(	0
11	0
/	0
57	0
[	0
19	0
%	0
]	0
vs	0
23	0
/	0
57	0
[	0
40	0
%	0
]	0
in	0
the	0
deep	0
sedation	0
group	0
;	0
P	0
=	0
.	0
02	0
)	0
,	0
indicating	0
that	0
1	0
incident	0
of	0
delirium	3
will	0
be	0
prevented	0
for	0
every	0
4	0
.	0
7	0
patients	0
treated	0
with	0
light	0
sedation	0
.	0

The	0
mean	0
+	0
/	0
-	0
SD	0
number	0
of	0
days	0
of	0
delirium	3
during	0
hospitalization	0
was	0
lower	0
in	0
the	0
light	0
sedation	0
group	0
than	0
in	0
the	0
deep	0
sedation	0
group	0
(	0
0	0
.	0
5	0
+	0
/	0
-	0
1	0
.	0
5	0
days	0
vs	0
1	0
.	0
4	0
+	0
/	0
-	0
4	0
.	0
0	0
days	0
;	0
P	0
=	0
.	0
01	0
)	0
.	0

C0NCLUSI0N	0
:	0
The	0
use	0
of	0
light	0
propofol	1
sedation	0
decreased	0
the	0
prevalence	0
of	0
postoperative	3
delirium	4
by	0
50	0
%	0
compared	0
with	0
deep	0
sedation	0
.	0

Limiting	0
depth	0
of	0
sedation	0
during	0
spinal	0
anesthesia	0
is	0
a	0
simple	0
,	0
safe	0
,	0
and	0
cost	0
-	0
effective	0
intervention	0
for	0
preventing	0
postoperative	3
delirium	4
in	0
elderly	0
patients	0
that	0
could	0
be	0
widely	0
and	0
readily	0
adopted	0
.	0

The	0
protective	0
role	0
of	0
Nrf2	0
in	0
streptozotocin	1
-	0
induced	0
diabetic	3
nephropathy	4
.	0

0BJECTIVE	0
:	0
Diabetic	3
nephropathy	4
is	0
one	0
of	0
the	0
major	0
causes	0
of	0
renal	3
failure	4
,	0
which	0
is	0
accompanied	0
by	0
the	0
production	0
of	0
reactive	0
oxygen	1
species	0
(	0
R0S	0
)	0
.	0

Nrf2	0
is	0
the	0
primary	0
transcription	0
factor	0
that	0
controls	0
the	0
antioxidant	0
response	0
essential	0
for	0
maintaining	0
cellular	0
redox	0
homeostasis	0
.	0

Here	0
,	0
we	0
report	0
our	0
findings	0
demonstrating	0
a	0
protective	0
role	0
of	0
Nrf2	0
against	0
diabetic	3
nephropathy	4
.	0

RESEARCH	0
DESIGN	0
AND	0
METH0DS	0
:	0
We	0
explore	0
the	0
protective	0
role	0
of	0
Nrf2	0
against	0
diabetic	3
nephropathy	4
using	0
human	0
kidney	0
biopsy	0
tissues	0
from	0
diabetic	3
nephropathy	4
patients	0
,	0
a	0
streptozotocin	1
-	0
induced	0
diabetic	3
nephropathy	4
model	0
in	0
Nrf2	0
(	0
-	0
/	0
-	0
)	0
mice	0
,	0
and	0
cultured	0
human	0
mesangial	0
cells	0
.	0

RESULTS	0
:	0
The	0
glomeruli	0
of	0
human	0
diabetic	3
nephropathy	4
patients	0
were	0
under	0
oxidative	0
stress	0
and	0
had	0
elevated	0
Nrf2	0
levels	0
.	0

In	0
the	0
animal	0
study	0
,	0
Nrf2	0
was	0
demonstrated	0
to	0
be	0
crucial	0
in	0
ameliorating	0
streptozotocin	1
-	0
induced	0
renal	3
damage	4
.	0

This	0
is	0
evident	0
by	0
Nrf2	0
(	0
-	0
/	0
-	0
)	0
mice	0
having	0
higher	0
R0S	0
production	0
and	0
suffering	0
from	0
greater	0
oxidative	0
DNA	0
damage	0
and	0
renal	3
injury	4
compared	0
with	0
Nrf2	0
(	0
+	0
/	0
+	0
)	0
mice	0
.	0

Mechanistic	0
studies	0
in	0
both	0
in	0
vivo	0
and	0
in	0
vitro	0
systems	0
showed	0
that	0
the	0
Nrf2	0
-	0
mediated	0
protection	0
against	0
diabetic	3
nephropathy	4
is	0
,	0
at	0
least	0
,	0
partially	0
through	0
inhibition	0
of	0
transforming	0
growth	0
factor	0
-	0
beta1	0
(	0
TGF	0
-	0
beta1	0
)	0
and	0
reduction	0
of	0
extracellular	0
matrix	0
production	0
.	0

In	0
human	0
renal	0
mesangial	0
cells	0
,	0
high	0
glucose	1
induced	0
R0S	0
production	0
and	0
activated	0
expression	0
of	0
Nrf2	0
and	0
its	0
downstream	0
genes	0
.	0

Furthermore	0
,	0
activation	0
or	0
overexpression	0
of	0
Nrf2	0
inhibited	0
the	0
promoter	0
activity	0
of	0
TGF	0
-	0
beta1	0
in	0
a	0
dose	0
-	0
dependent	0
manner	0
,	0
whereas	0
knockdown	0
of	0
Nrf2	0
by	0
siRNA	0
enhanced	0
TGF	0
-	0
beta1	0
transcription	0
and	0
fibronectin	0
production	0
.	0

C0NCLUSI0NS	0
:	0
This	0
work	0
clearly	0
indicates	0
a	0
protective	0
role	0
of	0
Nrf2	0
in	0
diabetic	3
nephropathy	4
,	0
suggesting	0
that	0
dietary	0
or	0
therapeutic	0
activation	0
of	0
Nrf2	0
could	0
be	0
used	0
as	0
a	0
strategy	0
to	0
prevent	0
or	0
slow	0
down	0
the	0
progression	0
of	0
diabetic	3
nephropathy	4
.	0

Metformin	1
prevents	0
experimental	0
gentamicin	1
-	0
induced	0
nephropathy	3
by	0
a	0
mitochondria	0
-	0
dependent	0
pathway	0
.	0

The	0
antidiabetic	0
drug	0
metformin	1
can	0
diminish	0
apoptosis	0
induced	0
by	0
oxidative	0
stress	0
in	0
endothelial	0
cells	0
and	0
prevent	0
vascular	3
dysfunction	4
even	0
in	0
nondiabetic	0
patients	0
.	0

Here	0
we	0
tested	0
whether	0
it	0
has	0
a	0
beneficial	0
effect	0
in	0
a	0
rat	0
model	0
of	0
gentamicin	1
toxicity	3
.	0

Mitochondrial	0
analysis	0
,	0
respiration	0
intensity	0
,	0
levels	0
of	0
reactive	0
oxygen	1
species	0
,	0
permeability	0
transition	0
,	0
and	0
cytochrome	0
c	0
release	0
were	0
assessed	0
3	0
and	0
6	0
days	0
after	0
gentamicin	1
administration	0
.	0

Metformin	1
treatment	0
fully	0
blocked	0
gentamicin	1
-	0
mediated	0
acute	3
renal	4
failure	4
.	0

This	0
was	0
accompanied	0
by	0
a	0
lower	0
activity	0
of	0
N	0
-	0
acetyl	0
-	0
beta	0
-	0
D	0
-	0
glucosaminidase	0
,	0
together	0
with	0
a	0
decrease	0
of	0
lipid	0
peroxidation	0
and	0
increase	0
of	0
antioxidant	0
systems	0
.	0

Metformin	1
also	0
protected	0
the	0
kidney	0
from	0
histological	0
damage	0
6	0
days	0
after	0
gentamicin	1
administration	0
.	0

These	0
in	0
vivo	0
markers	0
of	0
kidney	3
dysfunction	4
and	0
their	0
correction	0
by	0
metformin	1
were	0
complemented	0
by	0
in	0
vitro	0
studies	0
of	0
mitochondrial	0
function	0
.	0

We	0
found	0
that	0
gentamicin	1
treatment	0
depleted	0
respiratory	0
components	0
(	0
cytochrome	0
c	0
,	0
NADH	0
)	0
,	0
probably	0
due	0
to	0
the	0
opening	0
of	0
mitochondrial	0
transition	0
pores	0
.	0

These	0
injuries	0
,	0
partly	0
mediated	0
by	0
a	0
rise	0
in	0
reactive	0
oxygen	1
species	0
from	0
the	0
electron	0
transfer	0
chain	0
,	0
were	0
significantly	0
decreased	0
by	0
metformin	1
.	0

Thus	0
,	0
our	0
study	0
suggests	0
that	0
pleiotropic	0
effects	0
of	0
metformin	1
can	0
lessen	0
gentamicin	1
nephrotoxicity	3
and	0
improve	0
mitochondrial	0
homeostasis	0
.	0

Risk	0
of	0
nephropathy	3
after	0
consumption	0
of	0
nonionic	0
contrast	1
media	2
by	0
children	0
undergoing	0
cardiac	0
angiography	0
:	0
a	0
prospective	0
study	0
.	0

Despite	0
increasing	0
reports	0
on	0
nonionic	0
contrast	1
media	2
-	0
induced	0
nephropathy	3
(	0
CIN	3
)	0
in	0
hospitalized	0
adult	0
patients	0
during	0
cardiac	0
procedures	0
,	0
the	0
studies	0
in	0
pediatrics	0
are	0
limited	0
,	0
with	0
even	0
less	0
focus	0
on	0
possible	0
predisposing	0
factors	0
and	0
preventive	0
measures	0
for	0
patients	0
undergoing	0
cardiac	0
angiography	0
.	0

This	0
prospective	0
study	0
determined	0
the	0
incidence	0
of	0
CIN	3
for	0
two	0
nonionic	0
contrast	1
media	2
(	0
CM	1
)	0
,	0
iopromide	1
and	0
iohexol	1
,	0
among	0
80	0
patients	0
younger	0
than	0
18	0
years	0
and	0
compared	0
the	0
rates	0
for	0
this	0
complication	0
in	0
relation	0
to	0
the	0
type	0
and	0
dosage	0
of	0
CM	1
and	0
the	0
presence	0
of	0
cyanosis	3
.	0

The	0
80	0
patients	0
in	0
the	0
study	0
consecutively	0
received	0
either	0
iopromide	1
(	0
group	0
A	0
,	0
n	0
=	0
40	0
)	0
or	0
iohexol	1
(	0
group	0
B	0
,	0
n	0
=	0
40	0
)	0
.	0

Serum	0
sodium	1
(	0
Na	1
)	0
,	0
potassium	1
(	0
K	1
)	0
,	0
and	0
creatinine	1
(	0
Cr	1
)	0
were	0
measured	0
24	0
h	0
before	0
angiography	0
as	0
baseline	0
values	0
,	0
then	0
measured	0
again	0
at	0
12	0
-	0
,	0
24	0
-	0
,	0
and	0
48	0
-	0
h	0
intervals	0
after	0
CM	1
use	0
.	0

Urine	0
samples	0
for	0
Na	1
and	0
Cr	1
also	0
were	0
checked	0
at	0
the	0
same	0
intervals	0
.	0

Risk	0
of	0
renal	3
failure	4
,	0
Injury	3
to	4
the	4
kidney	4
,	0
Failure	3
of	4
kidney	4
function	4
,	0
Loss	3
of	4
kidney	4
function	4
,	0
and	0
End	0
-	0
stage	0
renal	3
damage	4
(	0
RIFLE	0
criteria	0
)	0
were	0
used	0
to	0
define	0
CIN	3
and	0
its	0
incidence	0
in	0
the	0
study	0
population	0
.	0

Accordingly	0
,	0
among	0
the	0
15	0
CIN	3
patients	0
(	0
18	0
.	0
75	0
%	0
)	0
,	0
7	0
.	0
5	0
%	0
of	0
the	0
patients	0
in	0
group	0
A	0
had	0
increased	0
risk	0
and	0
3	0
.	0
75	0
%	0
had	0
renal	3
injury	4
,	0
whereas	0
5	0
%	0
of	0
group	0
B	0
had	0
increased	0
risk	0
and	0
2	0
.	0
5	0
%	0
had	0
renal	3
injury	4
.	0

Whereas	0
33	0
.	0
3	0
%	0
of	0
the	0
patients	0
with	0
CIN	3
were	0
among	0
those	0
who	0
received	0
the	0
proper	0
dosage	0
of	0
CM	1
,	0
the	0
percentage	0
increased	0
to	0
66	0
.	0
6	0
%	0
among	0
those	0
who	0
received	0
larger	0
doses	0
,	0
with	0
a	0
significant	0
difference	0
in	0
the	0
incidence	0
of	0
CIN	3
related	0
to	0
the	0
different	0
dosages	0
of	0
CM	1
(	0
p	0
=	0
0	0
.	0
014	0
)	0
.	0

Among	0
the	0
15	0
patients	0
with	0
CIN	3
,	0
6	0
had	0
cyanotic	0
congenital	3
heart	4
diseases	4
,	0
but	0
the	0
incidence	0
did	0
not	0
differ	0
significantly	0
from	0
that	0
for	0
the	0
noncyanotic	0
patients	0
(	0
p	0
=	0
0	0
.	0
243	0
)	0
.	0

Although	0
clinically	0
silent	0
,	0
CIN	3
is	0
not	0
rare	0
in	0
pediatrics	0
.	0

The	0
incidence	0
depends	0
on	0
dosage	0
but	0
not	0
on	0
the	0
type	0
of	0
consumed	0
nonionic	0
CM	1
,	0
nor	0
on	0
the	0
presence	0
of	0
cyanosis	3
,	0
and	0
although	0
CIN	3
usually	0
is	0
reversible	0
,	0
more	0
concern	0
is	0
needed	0
for	0
the	0
prevention	0
of	0
such	0
a	0
complication	0
in	0
children	0
.	0

Renal	0
function	0
and	0
hemodynamics	0
during	0
prolonged	0
isoflurane	1
-	0
induced	0
hypotension	3
in	0
humans	0
.	0

The	0
effect	0
of	0
isoflurane	1
-	0
induced	0
hypotension	3
on	0
glomerular	0
function	0
and	0
renal	0
blood	0
flow	0
was	0
investigated	0
in	0
20	0
human	0
subjects	0
.	0

Glomerular	0
filtration	0
rate	0
(	0
GFR	0
)	0
and	0
effective	0
renal	0
plasma	0
flow	0
(	0
ERPF	0
)	0
were	0
measured	0
by	0
inulin	0
and	0
para	1
-	2
aminohippurate	2
(	0
PAH	1
)	0
clearance	0
,	0
respectively	0
.	0

Anesthesia	0
was	0
maintained	0
with	0
fentanyl	1
,	0
nitrous	1
oxide	2
,	0
oxygen	1
,	0
and	0
isoflurane	1
.	0

Hypotension	3
was	0
induced	0
for	0
236	0
.	0
9	0
+	0
/	0
-	0
15	0
.	0
1	0
min	0
by	0
increasing	0
the	0
isoflurane	1
inspired	0
concentration	0
to	0
maintain	0
a	0
mean	0
arterial	0
pressure	0
of	0
59	0
.	0
8	0
+	0
/	0
-	0
0	0
.	0
4	0
mmHg	0
.	0

GFR	0
and	0
ERPF	0
decreased	0
with	0
the	0
induction	0
of	0
anesthesia	0
but	0
not	0
significantly	0
more	0
during	0
hypotension	3
.	0

Postoperatively	0
,	0
ERPF	0
returned	0
to	0
preoperative	0
values	0
,	0
whereas	0
GFR	0
was	0
higher	0
than	0
preoperative	0
values	0
.	0

Renal	0
vascular	0
resistance	0
increased	0
during	0
anesthesia	0
but	0
decreased	0
when	0
hypotension	3
was	0
induced	0
,	0
allowing	0
the	0
maintenance	0
of	0
renal	0
blood	0
flow	0
.	0

We	0
conclude	0
that	0
renal	0
compensatory	0
mechanisms	0
are	0
preserved	0
during	0
isoflurane	1
-	0
induced	0
hypotension	3
and	0
that	0
renal	0
function	0
and	0
hemodynamics	0
quickly	0
return	0
to	0
normal	0
when	0
normotension	0
is	0
resumed	0
.	0

Brainstem	3
dysgenesis	4
in	0
an	0
infant	0
prenatally	0
exposed	0
to	0
cocaine	1
.	0

Many	0
authors	0
described	0
the	0
effects	0
on	0
the	0
fetus	0
of	0
maternal	0
cocaine	3
abuse	4
during	0
pregnancy	0
.	0

Vasoconstriction	0
appears	0
to	0
be	0
the	0
common	0
mechanism	0
of	0
action	0
leading	0
to	0
a	0
wide	0
range	0
of	0
fetal	3
anomalies	4
.	0

We	0
report	0
on	0
an	0
infant	0
with	0
multiple	3
cranial	4
-	4
nerve	4
involvement	4
attributable	0
to	0
brainstem	3
dysgenesis	4
,	0
born	0
to	0
a	0
cocaine	3
-	4
addicted	4
mother	0
.	0

A	0
cross	0
-	0
sectional	0
evaluation	0
of	0
the	0
effect	0
of	0
risperidone	1
and	0
selective	0
serotonin	1
reuptake	0
inhibitors	0
on	0
bone	0
mineral	0
density	0
in	0
boys	0
.	0

0BJECTIVE	0
:	0
The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
investigate	0
the	0
effect	0
of	0
risperidone	1
-	0
induced	0
hyperprolactinemia	3
on	0
trabecular	0
bone	0
mineral	0
density	0
(	0
BMD	0
)	0
in	0
children	0
and	0
adolescents	0
.	0

METH0D	0
:	0
Medically	0
healthy	0
7	0
-	0
to	0
17	0
-	0
year	0
-	0
old	0
males	0
chronically	0
treated	0
,	0
in	0
a	0
naturalistic	0
setting	0
,	0
with	0
risperidone	1
were	0
recruited	0
for	0
this	0
cross	0
-	0
sectional	0
study	0
through	0
child	0
psychiatry	0
outpatient	0
clinics	0
between	0
November	0
2005	0
and	0
June	0
2007	0
.	0

Anthropometric	0
measurements	0
and	0
laboratory	0
testing	0
were	0
conducted	0
.	0

The	0
clinical	0
diagnoses	0
were	0
based	0
on	0
chart	0
review	0
,	0
and	0
developmental	0
and	0
treatment	0
history	0
was	0
obtained	0
from	0
the	0
medical	0
record	0
.	0

Volumetric	0
BMD	0
of	0
the	0
ultradistal	0
radius	0
was	0
measured	0
using	0
peripheral	0
quantitative	0
computed	0
tomography	0
,	0
and	0
areal	0
BMD	0
of	0
the	0
lumbar	0
spine	0
was	0
estimated	0
using	0
dual	0
-	0
energy	0
x	0
-	0
ray	0
absorptiometry	0
.	0

RESULTS	0
:	0
Hyperprolactinemia	3
was	0
present	0
in	0
49	0
%	0
of	0
83	0
boys	0
(	0
n	0
=	0
41	0
)	0
treated	0
with	0
risperidone	1
for	0
a	0
mean	0
of	0
2	0
.	0
9	0
years	0
.	0

Serum	0
testosterone	1
concentration	0
increased	0
with	0
pubertal	0
status	0
but	0
was	0
not	0
affected	0
by	0
hyperprolactinemia	3
.	0

As	0
expected	0
,	0
bone	0
mineral	0
content	0
and	0
BMD	0
increased	0
with	0
sexual	0
maturity	0
.	0

After	0
adjusting	0
for	0
the	0
stage	0
of	0
sexual	0
development	0
and	0
height	0
and	0
BMI	0
z	0
scores	0
,	0
serum	0
prolactin	0
was	0
negatively	0
associated	0
with	0
trabecular	0
volumetric	0
BMD	0
at	0
the	0
ultradistal	0
radius	0
(	0
P	0
<	0
.	0
03	0
)	0
.	0

Controlling	0
for	0
relevant	0
covariates	0
,	0
we	0
also	0
found	0
treatment	0
with	0
selective	0
serotonin	1
reuptake	0
inhibitors	0
(	0
SSRIs	0
)	0
to	0
be	0
associated	0
with	0
lower	0
trabecular	0
BMD	0
at	0
the	0
radius	0
(	0
P	0
=	0
.	0
03	0
)	0
and	0
BMD	0
z	0
score	0
at	0
the	0
lumbar	0
spine	0
(	0
P	0
<	0
.	0
05	0
)	0
.	0

These	0
findings	0
became	0
more	0
marked	0
when	0
the	0
analysis	0
was	0
restricted	0
to	0
non	0
-	0
Hispanic	0
white	0
patients	0
.	0

0f	0
13	0
documented	0
fractures	3
,	0
3	0
occurred	0
after	0
risperidone	1
and	0
SSRIs	0
were	0
started	0
,	0
and	0
none	0
occurred	0
in	0
patients	0
with	0
hyperprolactinemia	3
.	0

C0NCLUSI0NS	0
:	0
This	0
is	0
the	0
first	0
study	0
to	0
link	0
risperidone	1
-	0
induced	0
hyperprolactinemia	3
and	0
SSRI	0
treatment	0
to	0
lower	0
BMD	0
in	0
children	0
and	0
adolescents	0
.	0

Future	0
research	0
should	0
evaluate	0
the	0
longitudinal	0
course	0
of	0
this	0
adverse	0
event	0
to	0
determine	0
its	0
temporal	0
stability	0
and	0
whether	0
a	0
higher	0
fracture	0
rate	0
ensues	0
.	0

Fear	0
-	0
potentiated	0
startle	3
,	0
but	0
not	0
light	0
-	0
enhanced	0
startle	3
,	0
is	0
enhanced	0
by	0
anxiogenic	0
drugs	0
.	0

RATI0NALE	0
AND	0
0BJECTIVES	0
:	0
The	0
light	0
-	0
enhanced	0
startle	3
paradigm	0
(	0
LES	0
)	0
is	0
suggested	0
to	0
model	0
anxiety	3
,	0
because	0
of	0
the	0
non	0
-	0
specific	0
cue	0
and	0
the	0
long	0
-	0
term	0
effect	0
.	0

In	0
contrast	0
,	0
the	0
fear	0
-	0
potentiated	0
startle	3
(	0
FPS	0
)	0
is	0
suggested	0
to	0
model	0
conditioned	0
fear	0
.	0

However	0
,	0
the	0
pharmacological	0
profiles	0
of	0
these	0
two	0
paradigms	0
are	0
very	0
similar	0
.	0

The	0
present	0
study	0
investigated	0
the	0
effects	0
of	0
putative	0
anxiogenic	0
drugs	0
on	0
LES	0
and	0
FPS	0
and	0
aimed	0
at	0
determining	0
the	0
sensitivity	0
of	0
LES	0
for	0
anxiogenic	0
drugs	0
and	0
to	0
potentially	0
showing	0
a	0
pharmacological	0
differentiation	0
between	0
these	0
two	0
paradigms	0
.	0

METH0DS	0
:	0
Male	0
Wistar	0
rats	0
received	0
each	0
dose	0
of	0
the	0
alpha	0
(	0
2	0
)	0
-	0
adrenoceptor	0
antagonist	0
yohimbine	1
(	0
0	0
.	0
25	0
-	0
1	0
.	0
0mg	0
/	0
kg	0
)	0
,	0
the	0
5	1
-	2
HT	2
(	0
2C	0
)	0
receptor	0
agonist	0
m	1
-	2
chlorophenylpiperazine	2
(	0
mCPP	1
,	0
0	0
.	0
5	0
-	0
2	0
.	0
0mg	0
/	0
kg	0
)	0
or	0
the	0
GABA	1
(	0
A	0
)	0
inverse	0
receptor	0
agonist	0
pentylenetetrazole	1
(	0
PTZ	1
,	0
3	0
-	0
30mg	0
/	0
kg	0
)	0
and	0
were	0
subsequently	0
tested	0
in	0
either	0
LES	0
or	0
FPS	0
.	0

RESULTS	0
:	0
None	0
of	0
the	0
drugs	0
enhanced	0
LES	0
,	0
whereas	0
mCPP	1
increased	0
percentage	0
FPS	0
and	0
yohimbine	1
increased	0
absolute	0
FPS	0
values	0
.	0

Furthermore	0
,	0
yohimbine	1
increased	0
baseline	0
startle	3
amplitude	0
in	0
the	0
LES	0
,	0
while	0
mCPP	1
suppressed	0
baseline	0
startle	3
in	0
both	0
the	0
LES	0
and	0
FPS	0
and	0
PTZ	1
suppressed	0
baseline	0
startle	3
in	0
the	0
FPS	0
.	0

C0NCLUSI0NS	0
:	0
In	0
contrast	0
to	0
findings	0
in	0
the	0
FPS	0
paradigm	0
,	0
none	0
of	0
the	0
drugs	0
were	0
able	0
to	0
exacerbate	0
the	0
LES	0
response	0
.	0

Thus	0
,	0
a	0
clear	0
pharmacological	0
differentiation	0
was	0
found	0
between	0
LES	0
and	0
FPS	0
.	0

Rosaceiform	0
dermatitis	3
associated	0
with	0
topical	0
tacrolimus	1
treatment	0
.	0

We	0
describe	0
herein	0
3	0
patients	0
who	0
developed	0
rosacea	3
-	0
like	0
dermatitis	3
eruptions	3
while	0
using	0
0	0
.	0
03	0
%	0
or	0
0	0
.	0
1	0
%	0
tacrolimus	1
ointment	0
for	0
facial	3
dermatitis	4
.	0

Skin	0
biopsy	0
specimens	0
showed	0
telangiectasia	3
and	0
noncaseating	0
epithelioid	0
granulomatous	0
tissue	0
formation	0
in	0
the	0
papillary	0
to	0
mid	0
dermis	0
.	0

Continuous	0
topical	0
use	0
of	0
immunomodulators	0
such	0
as	0
tacrolimus	1
or	0
pimecrolimus	1
should	0
be	0
regarded	0
as	0
a	0
potential	0
cause	0
of	0
rosaceiform	0
dermatitis	3
,	0
although	0
many	0
cases	0
have	0
not	0
been	0
reported	0
.	0

Coenzyme	1
Q10	2
treatment	0
ameliorates	0
acute	0
cisplatin	1
nephrotoxicity	3
in	0
mice	0
.	0

The	0
nephroprotective	0
effect	0
of	0
coenzyme	1
Q10	2
was	0
investigated	0
in	0
mice	0
with	0
acute	3
renal	4
injury	4
induced	0
by	0
a	0
single	0
i	0
.	0
p	0
.	0
injection	0
of	0
cisplatin	1
(	0
5	0
mg	0
/	0
kg	0
)	0
.	0

Coenzyme	1
Q10	2
treatment	0
(	0
10	0
mg	0
/	0
kg	0
/	0
day	0
,	0
i	0
.	0
p	0
.	0
)	0
was	0
applied	0
for	0
6	0
consecutive	0
days	0
,	0
starting	0
1	0
day	0
before	0
cisplatin	1
administration	0
.	0

Coenzyme	1
Q10	2
significantly	0
reduced	0
blood	1
urea	2
nitrogen	2
and	0
serum	0
creatinine	1
levels	0
which	0
were	0
increased	0
by	0
cisplatin	1
.	0

Coenzyme	1
Q10	2
significantly	0
compensated	0
deficits	0
in	0
the	0
antioxidant	0
defense	0
mechanisms	0
(	0
reduced	1
glutathione	2
level	0
and	0
superoxide	1
dismutase	0
activity	0
)	0
,	0
suppressed	0
lipid	0
peroxidation	0
,	0
decreased	0
the	0
elevations	0
of	0
tumor	3
necrosis	3
factor	0
-	0
alpha	0
,	0
nitric	1
oxide	2
and	0
platinum	1
ion	0
concentration	0
,	0
and	0
attenuated	0
the	0
reductions	0
of	0
selenium	1
and	0
zinc	1
ions	0
in	0
renal	0
tissue	0
resulted	0
from	0
cisplatin	1
administration	0
.	0

Also	0
,	0
histopathological	0
renal	3
tissue	4
damage	4
mediated	0
by	0
cisplatin	1
was	0
ameliorated	0
by	0
coenzyme	1
Q10	2
treatment	0
.	0

Immunohistochemical	0
analysis	0
revealed	0
that	0
coenzyme	1
Q10	2
significantly	0
decreased	0
the	0
cisplatin	1
-	0
induced	0
overexpression	0
of	0
inducible	0
nitric	1
oxide	2
synthase	0
,	0
nuclear	0
factor	0
-	0
kappaB	0
,	0
caspase	0
-	0
3	0
and	0
p53	0
in	0
renal	0
tissue	0
.	0

It	0
was	0
concluded	0
that	0
coenzyme	1
Q10	2
represents	0
a	0
potential	0
therapeutic	0
option	0
to	0
protect	0
against	0
acute	0
cisplatin	1
nephrotoxicity	3
commonly	0
encountered	0
in	0
clinical	0
practice	0
.	0

Reversible	0
cholestasis	3
with	0
bile	3
duct	4
injury	4
following	0
azathioprine	1
therapy	0
.	0

A	0
case	0
report	0
.	0

A	0
67	0
-	0
year	0
-	0
old	0
patient	0
,	0
with	0
primary	0
polymyositis	3
and	0
without	0
previous	0
evidence	0
of	0
liver	3
disease	4
,	0
developed	0
clinical	0
and	0
biochemical	0
features	0
of	0
severe	0
cholestasis	3
3	0
months	0
after	0
initiation	0
of	0
azathioprine	1
therapy	0
.	0

Liver	0
biopsy	0
showed	0
cholestasis	3
with	0
both	0
cytological	0
and	0
architectural	0
alterations	0
of	0
interlobular	0
bile	0
ducts	0
.	0

Azathioprine	1
withdrawal	0
resulted	0
after	0
7	0
weeks	0
in	0
the	0
resolution	0
of	0
clinical	0
and	0
biochemical	0
abnormalities	0
.	0

It	0
is	0
believed	0
that	0
this	0
is	0
the	0
first	0
reported	0
case	0
of	0
reversible	0
azathioprine	1
-	0
induced	0
cholestasis	3
associated	0
with	0
histological	0
evidence	0
of	0
bile	3
duct	4
injury	4
.	0

Dopamine	1
is	0
not	0
essential	0
for	0
the	0
development	0
of	0
methamphetamine	1
-	0
induced	0
neurotoxicity	3
.	0

It	0
is	0
widely	0
believed	0
that	0
dopamine	1
(	0
DA	1
)	0
mediates	0
methamphetamine	1
(	0
METH	1
)	0
-	0
induced	0
toxicity	3
to	0
brain	0
dopaminergic	0
neurons	0
,	0
because	0
drugs	0
that	0
interfere	0
with	0
DA	1
neurotransmission	0
decrease	0
toxicity	3
,	0
whereas	0
drugs	0
that	0
increase	0
DA	1
neurotransmission	0
enhance	0
toxicity	3
.	0

However	0
,	0
temperature	0
effects	0
of	0
drugs	0
that	0
have	0
been	0
used	0
to	0
manipulate	0
brain	0
DA	1
neurotransmission	0
confound	0
interpretation	0
of	0
the	0
data	0
.	0

Here	0
we	0
show	0
that	0
the	0
recently	0
reported	0
ability	0
of	0
L	1
-	2
dihydroxyphenylalanine	2
to	0
reverse	0
the	0
protective	0
effect	0
of	0
alpha	1
-	2
methyl	2
-	2
para	2
-	2
tyrosine	2
on	0
METH	1
-	0
induced	0
DA	1
neurotoxicity	3
is	0
also	0
confounded	0
by	0
drug	0
effects	0
on	0
body	0
temperature	0
.	0

Further	0
,	0
we	0
show	0
that	0
mice	0
genetically	0
engineered	0
to	0
be	0
deficient	0
in	0
brain	0
DA	1
develop	0
METH	1
neurotoxicity	3
,	0
as	0
long	0
as	0
the	0
thermic	0
effects	0
of	0
METH	1
are	0
preserved	0
.	0

In	0
addition	0
,	0
we	0
demonstrate	0
that	0
mice	0
genetically	0
engineered	0
to	0
have	0
unilateral	0
brain	0
DA	1
deficits	0
develop	0
METH	1
-	0
induced	0
dopaminergic	3
deficits	4
that	0
are	0
of	0
comparable	0
magnitude	0
on	0
both	0
sides	0
of	0
the	0
brain	0
.	0

Taken	0
together	0
,	0
these	0
findings	0
demonstrate	0
that	0
DA	1
is	0
not	0
essential	0
for	0
the	0
development	0
of	0
METH	1
-	0
induced	0
dopaminergic	0
neurotoxicity	3
and	0
suggest	0
that	0
mechanisms	0
independent	0
of	0
DA	1
warrant	0
more	0
intense	0
investigation	0
.	0

Swallowing	0
-	0
induced	0
atrial	3
tachyarrhythmia	4
triggered	0
by	0
salbutamol	1
:	0
case	0
report	0
and	0
review	0
of	0
the	0
literature	0
.	0

CASE	0
:	0
A	0
49	0
-	0
year	0
-	0
old	0
patient	0
experienced	0
chest	0
discomfort	0
while	0
swallowing	0
.	0

0n	0
electrocardiogram	0
,	0
episodes	0
of	0
atrial	3
tachyarrhythmia	4
were	0
recorded	0
immediately	0
after	0
swallowing	0
;	0
24	0
-	0
hour	0
Holter	0
monitoring	0
recorded	0
several	0
events	0
.	0

The	0
arrhythmia	3
resolved	0
after	0
therapy	0
with	0
atenolol	1
,	0
but	0
recurred	0
a	0
year	0
later	0
.	0

The	0
patient	0
noticed	0
that	0
before	0
these	0
episodes	0
he	0
had	0
been	0
using	0
an	0
inhalator	0
of	0
salbutamol	1
.	0

After	0
stopping	0
the	0
beta	0
-	0
agonist	0
,	0
and	0
after	0
a	0
week	0
with	0
the	0
atenolol	1
,	0
the	0
arrhythmia	3
disappeared	0
.	0

DISCUSSI0N	0
:	0
Swallowing	0
-	0
induced	0
atrial	3
tachyarrhythmia	4
(	0
SIAT	3
)	0
is	0
a	0
rare	0
phenomenon	0
.	0

Fewer	0
than	0
50	0
cases	0
of	0
SIAT	3
have	0
been	0
described	0
in	0
the	0
literature	0
.	0

This	0
article	0
summarizes	0
all	0
the	0
cases	0
published	0
,	0
creating	0
a	0
comprehensive	0
review	0
of	0
the	0
current	0
knowledge	0
and	0
approach	0
to	0
SIAT	3
.	0

It	0
discusses	0
demographics	0
,	0
clinical	0
characteristics	0
and	0
types	0
of	0
arrhythmia	3
,	0
postulated	0
mechanisms	0
of	0
SIAT	3
,	0
and	0
different	0
treatment	0
possibilities	0
such	0
as	0
medications	0
,	0
surgery	0
,	0
and	0
radiofrequency	0
catheter	0
ablation	0
(	0
RFCA	0
)	0
.	0

C0NCLUSI0N	0
:	0
Salbutamol	1
is	0
presented	0
here	0
as	0
a	0
possible	0
trigger	0
for	0
SIAT	3
.	0

Although	0
it	0
is	0
difficult	0
to	0
define	0
causality	0
in	0
a	0
case	0
report	0
,	0
it	0
is	0
logical	0
to	0
think	0
that	0
a	0
beta	0
-	0
agonist	0
like	0
salbutamol	1
(	0
known	0
to	0
induce	0
tachycardia	3
)	0
may	0
be	0
the	0
trigger	0
of	0
adrenergic	0
reflexes	0
originating	0
in	0
the	0
esophagus	0
while	0
swallowing	0
and	0
that	0
a	0
beta	0
-	0
blocker	0
such	0
as	0
atenolol	1
(	0
that	0
blocks	0
the	0
adrenergic	0
activity	0
)	0
may	0
relieve	0
it	0
.	0

The	0
ability	0
of	0
insulin	0
treatment	0
to	0
reverse	0
or	0
prevent	0
the	0
changes	0
in	0
urinary	0
bladder	0
function	0
caused	0
by	0
streptozotocin	1
-	0
induced	0
diabetes	3
mellitus	4
.	0

1	0
.	0

The	0
effects	0
of	0
insulin	0
treatment	0
on	0
in	0
vivo	0
and	0
in	0
vitro	0
urinary	0
bladder	0
function	0
in	0
streptozotocin	1
-	0
diabetic	3
rats	0
were	0
investigated	0
.	0

2	0
.	0

Diabetes	3
of	0
2	0
months	0
duration	0
resulted	0
in	0
decreases	0
in	0
body	0
weight	0
and	0
increases	0
in	0
fluid	0
consumption	0
,	0
urine	0
volume	0
,	0
frequency	0
of	0
micturition	0
,	0
and	0
average	0
volume	0
per	0
micturition	0
;	0
effects	0
which	0
were	0
prevented	0
by	0
insulin	0
treatment	0
.	0

3	0
.	0

Insulin	0
treatment	0
also	0
prevented	0
the	0
increases	0
in	0
contractile	0
responses	0
of	0
bladder	0
body	0
strips	0
from	0
diabetic	3
rats	0
to	0
nerve	0
stimulation	0
,	0
ATP	1
,	0
and	0
bethanechol	1
.	0

4	0
.	0

Diabetes	3
of	0
4	0
months	0
duration	0
also	0
resulted	0
in	0
decreases	0
in	0
body	0
weight	0
,	0
and	0
increases	0
in	0
fluid	0
consumption	0
,	0
urine	0
volume	0
,	0
frequency	0
of	0
micturition	0
,	0
and	0
average	0
volume	0
per	0
micturition	0
,	0
effects	0
which	0
were	0
reversed	0
by	0
insulin	0
treatment	0
for	0
the	0
final	0
2	0
months	0
of	0
the	0
study	0
.	0

5	0
.	0

Insulin	0
treatment	0
reversed	0
the	0
increases	0
in	0
contractile	0
responses	0
of	0
bladder	0
body	0
strips	0
from	0
diabetic	3
rats	0
to	0
nerve	0
stimulation	0
,	0
ATP	1
,	0
and	0
bethanechol	1
.	0

6	0
.	0

The	0
data	0
indicate	0
that	0
the	0
effects	0
of	0
streptozotocin	1
-	0
induced	0
diabetes	3
on	0
urinary	0
bladder	0
function	0
are	0
both	0
prevented	0
and	0
reversed	0
by	0
insulin	0
treatment	0
.	0

Glutamatergic	0
neurotransmission	0
mediated	0
by	0
NMDA	1
receptors	0
in	0
the	0
inferior	0
colliculus	0
can	0
modulate	0
haloperidol	1
-	0
induced	0
catalepsy	3
.	0

The	0
inferior	0
colliculus	0
(	0
IC	0
)	0
is	0
primarily	0
involved	0
in	0
the	0
processing	0
of	0
auditory	0
information	0
,	0
but	0
it	0
is	0
distinguished	0
from	0
other	0
auditory	0
nuclei	0
in	0
the	0
brainstem	0
by	0
its	0
connections	0
with	0
structures	0
of	0
the	0
motor	0
system	0
.	0

Functional	0
evidence	0
relating	0
the	0
IC	0
to	0
motor	0
behavior	0
derives	0
from	0
experiments	0
showing	0
that	0
activation	0
of	0
the	0
IC	0
by	0
electrical	0
stimulation	0
or	0
excitatory	0
amino	1
acid	2
microinjection	0
causes	0
freezing	0
,	0
escape	0
-	0
like	0
behavior	0
,	0
and	0
immobility	0
.	0

However	0
,	0
the	0
nature	0
of	0
this	0
immobility	0
is	0
still	0
unclear	0
.	0

The	0
present	0
study	0
examined	0
the	0
influence	0
of	0
excitatory	0
amino	1
acid	2
-	0
mediated	0
mechanisms	0
in	0
the	0
IC	0
on	0
the	0
catalepsy	3
induced	0
by	0
the	0
dopamine	1
receptor	0
blocker	0
haloperidol	1
administered	0
systemically	0
(	0
1	0
or	0
0	0
.	0
5	0
mg	0
/	0
kg	0
)	0
in	0
rats	0
.	0

Haloperidol	1
-	0
induced	0
catalepsy	3
was	0
challenged	0
with	0
prior	0
intracollicular	0
microinjections	0
of	0
glutamate	1
NMDA	1
receptor	0
antagonists	0
,	0
MK	1
-	2
801	2
(	0
15	0
or	0
30	0
mmol	0
/	0
0	0
.	0
5	0
microl	0
)	0
and	0
AP7	1
(	0
10	0
or	0
20	0
nmol	0
/	0
0	0
.	0
5	0
microl	0
)	0
,	0
or	0
of	0
the	0
NMDA	1
receptor	0
agonist	0
N	1
-	2
methyl	2
-	2
d	2
-	2
aspartate	2
(	0
NMDA	1
,	0
20	0
or	0
30	0
nmol	0
/	0
0	0
.	0
5	0
microl	0
)	0
.	0

The	0
results	0
showed	0
that	0
intracollicular	0
microinjection	0
of	0
MK	1
-	2
801	2
and	0
AP7	1
previous	0
to	0
systemic	0
injections	0
of	0
haloperidol	1
significantly	0
attenuated	0
the	0
catalepsy	3
,	0
as	0
indicated	0
by	0
a	0
reduced	0
latency	0
to	0
step	0
down	0
from	0
a	0
horizontal	0
bar	0
.	0

Accordingly	0
,	0
intracollicular	0
microinjection	0
of	0
NMDA	1
increased	0
the	0
latency	0
to	0
step	0
down	0
the	0
bar	0
.	0

These	0
findings	0
suggest	0
that	0
glutamate	1
-	0
mediated	0
mechanisms	0
in	0
the	0
neural	0
circuits	0
at	0
the	0
IC	0
level	0
influence	0
haloperidol	1
-	0
induced	0
catalepsy	3
and	0
participate	0
in	0
the	0
regulation	0
of	0
motor	0
activity	0
.	0

Severe	0
congestive	3
heart	4
failure	4
patient	0
on	0
amiodarone	1
presenting	0
with	0
myxedemic	3
coma	4
:	0
a	0
case	0
report	0
.	0

This	0
is	0
a	0
case	0
report	0
of	0
myxedema	3
coma	4
secondary	0
to	0
amiodarone	1
-	0
induced	0
hypothyroidism	3
in	0
a	0
patient	0
with	0
severe	0
congestive	3
heart	4
failure	4
(	0
CHF	3
)	0
.	0

To	0
our	0
knowledge	0
and	0
after	0
reviewing	0
the	0
literature	0
there	0
is	0
one	0
case	0
report	0
of	0
myxedema	3
coma	4
during	0
long	0
term	0
amiodarone	1
therapy	0
.	0

Myxedema	3
coma	4
is	0
a	0
life	0
threatening	0
condition	0
that	0
carries	0
a	0
mortality	0
reaching	0
as	0
high	0
as	0
20	0
%	0
with	0
treatment	0
.	0

The	0
condition	0
is	0
treated	0
with	0
intravenous	0
thyroxine	1
(	0
T4	1
)	0
or	0
intravenous	0
tri	1
-	2
iodo	2
-	2
thyronine	2
(	0
T3	1
)	0
.	0

Patients	0
with	0
CHF	3
on	0
amiodarone	1
may	0
suffer	0
serious	0
morbidity	0
and	0
mortality	0
from	0
hypothyroidism	3
,	0
and	0
thus	0
may	0
deserve	0
closer	0
follow	0
up	0
for	0
thyroid	0
stimulating	0
hormone	0
(	0
TSH	0
)	0
levels	0
.	0

This	0
case	0
report	0
carries	0
an	0
important	0
clinical	0
application	0
given	0
the	0
frequent	0
usage	0
of	0
amiodarone	1
among	0
CHF	3
patients	0
.	0

The	0
myriad	0
clinical	0
presentation	0
of	0
myxedema	3
coma	4
and	0
its	0
serious	0
morbidity	0
and	0
mortality	0
stresses	0
the	0
need	0
to	0
suspect	0
this	0
clinical	0
syndrome	0
among	0
CHF	3
patients	0
presenting	0
with	0
hypotension	3
,	0
weakness	3
or	0
other	0
unexplained	0
symptoms	0
.	0

Effects	0
of	0
active	0
constituents	0
of	0
Crocus	0
sativus	0
L	0
.	0
,	0
crocin	1
on	0
streptozocin	1
-	0
induced	0
model	0
of	0
sporadic	0
Alzheimer	3
'	4
s	4
disease	4
in	0
male	0
rats	0
.	0

BACKGR0UND	0
:	0
The	0
involvement	0
of	0
water	0
-	0
soluble	0
carotenoids	1
,	0
crocins	1
,	0
as	0
the	0
main	0
and	0
active	0
components	0
of	0
Crocus	0
sativus	0
L	0
.	0
extract	0
in	0
learning	0
and	0
memory	0
processes	0
has	0
been	0
proposed	0
.	0

In	0
the	0
present	0
study	0
,	0
the	0
effect	0
of	0
crocins	1
on	0
sporadic	0
Alzheimer	3
'	4
s	4
disease	4
induced	0
by	0
intracerebroventricular	0
(	0
icv	0
)	0
streptozocin	1
(	0
STZ	1
)	0
in	0
male	0
rats	0
was	0
investigated	0
.	0

METH0DS	0
:	0
Male	0
adult	0
Wistar	0
rats	0
(	0
n	0
=	0
90	0
and	0
260	0
-	0
290	0
g	0
)	0
were	0
divided	0
into	0
1	0
,	0
control	0
;	0
2	0
and	0
3	0
,	0
crocins	1
(	0
15	0
and	0
30	0
mg	0
/	0
kg	0
)	0
;	0
4	0
,	0
STZ	1
;	0
5	0
and	0
6	0
,	0
STZ	1
+	0
crocins	1
(	0
15	0
and	0
30	0
mg	0
/	0
kg	0
)	0
groups	0
.	0

In	0
Alzheimer	3
'	4
s	4
disease	4
groups	0
,	0
rats	0
were	0
injected	0
with	0
STZ	1
-	0
icv	0
bilaterally	0
(	0
3	0
mg	0
/	0
kg	0
)	0
in	0
first	0
day	0
and	0
3	0
days	0
later	0
,	0
a	0
similar	0
STZ	1
-	0
icv	0
application	0
was	0
repeated	0
.	0

In	0
STZ	1
+	0
crocin	1
animal	0
groups	0
,	0
crocin	1
was	0
applied	0
in	0
doses	0
of	0
15	0
and	0
30	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
,	0
one	0
day	0
pre	0
-	0
surgery	0
and	0
continued	0
for	0
three	0
weeks	0
.	0

Prescription	0
of	0
crocin	1
in	0
each	0
dose	0
was	0
repeated	0
once	0
for	0
two	0
days	0
.	0

However	0
,	0
the	0
learning	0
and	0
memory	0
performance	0
was	0
assessed	0
using	0
passive	0
avoidance	0
paradigm	0
,	0
and	0
for	0
spatial	0
cognition	0
evaluation	0
,	0
Y	0
-	0
maze	0
task	0
was	0
used	0
.	0

RESULTS	0
:	0
It	0
was	0
found	0
out	0
that	0
crocin	1
(	0
30	0
mg	0
/	0
kg	0
)	0
-	0
treated	0
STZ	1
-	0
injected	0
rats	0
show	0
higher	0
correct	0
choices	0
and	0
lower	0
errors	0
in	0
Y	0
-	0
maze	0
than	0
vehicle	0
-	0
treated	0
STZ	1
-	0
injected	0
rats	0
.	0

In	0
addition	0
,	0
crocin	1
in	0
the	0
mentioned	0
dose	0
could	0
significantly	0
attenuated	0
learning	3
and	4
memory	4
impairment	4
in	0
treated	0
STZ	1
-	0
injected	0
group	0
in	0
passive	0
avoidance	0
test	0
.	0

C0NCLUSI0N	0
:	0
Therefore	0
,	0
these	0
results	0
demonstrate	0
the	0
effectiveness	0
of	0
crocin	1
(	0
30	0
mg	0
/	0
kg	0
)	0
in	0
antagonizing	0
the	0
cognitive	3
deficits	4
caused	0
by	0
STZ	1
-	0
icv	0
in	0
rats	0
and	0
its	0
potential	0
in	0
the	0
treatment	0
of	0
neurodegenerative	3
diseases	4
such	0
as	0
Alzheimer	3
'	4
s	4
disease	4
.	0

Serotonin	1
6	0
receptor	0
gene	0
is	0
associated	0
with	0
methamphetamine	1
-	0
induced	0
psychosis	3
in	0
a	0
Japanese	0
population	0
.	0

BACKGR0UND	0
:	0
Altered	0
serotonergic	0
neural	0
transmission	0
is	0
hypothesized	0
to	0
be	0
a	0
susceptibility	0
factor	0
for	0
psychotic	3
disorders	4
such	0
as	0
schizophrenia	3
.	0

The	0
serotonin	1
6	0
(	0
5	1
-	2
HT6	2
)	0
receptor	0
is	0
therapeutically	0
targeted	0
by	0
several	0
second	0
generation	0
antipsychotics	0
,	0
such	0
as	0
clozapine	1
and	0
olanzapine	1
,	0
and	0
d	1
-	2
amphetamine	2
-	0
induced	0
hyperactivity	3
in	0
rats	0
is	0
corrected	0
with	0
the	0
use	0
of	0
a	0
selective	0
5	1
-	2
HT6	2
receptor	0
antagonist	0
.	0

In	0
addition	0
,	0
the	0
disrupted	0
prepulse	0
inhibition	0
induced	0
by	0
d	1
-	2
amphetamine	2
or	0
phencyclidine	1
was	0
restored	0
by	0
5	1
-	2
HT6	2
receptor	0
antagonist	0
in	0
an	0
animal	0
study	0
using	0
rats	0
.	0

These	0
animal	0
models	0
were	0
considered	0
to	0
reflect	0
the	0
positive	0
symptoms	0
of	0
schizophrenia	3
,	0
and	0
the	0
above	0
evidence	0
suggests	0
that	0
altered	0
5	1
-	2
HT6	2
receptors	0
are	0
involved	0
in	0
the	0
pathophysiology	0
of	0
psychotic	3
disorders	4
.	0

The	0
symptoms	0
of	0
methamphetamine	1
(	0
METH	1
)	0
-	0
induced	0
psychosis	3
are	0
similar	0
to	0
those	0
of	0
paranoid	3
type	4
schizophrenia	4
.	0

Therefore	0
,	0
we	0
conducted	0
an	0
analysis	0
of	0
the	0
association	0
of	0
the	0
5	1
-	2
HT6	2
gene	0
(	0
HTR6	0
)	0
with	0
METH	1
-	0
induced	0
psychosis	3
.	0

METH0D	0
:	0
Using	0
five	0
tagging	0
SNPs	0
(	0
rs6693503	0
,	0
rs1805054	0
,	0
rs4912138	0
,	0
rs3790757	0
and	0
rs9659997	0
)	0
,	0
we	0
conducted	0
a	0
genetic	0
association	0
analysis	0
of	0
case	0
-	0
control	0
samples	0
(	0
197	0
METH	1
-	0
induced	0
psychosis	3
patients	0
and	0
337	0
controls	0
)	0
in	0
the	0
Japanese	0
population	0
.	0

The	0
age	0
and	0
sex	0
of	0
the	0
control	0
subjects	0
did	0
not	0
differ	0
from	0
those	0
of	0
the	0
methamphetamine	1
dependence	0
patients	0
.	0

RESULTS	0
:	0
rs6693503	0
was	0
associated	0
with	0
METH	1
-	0
induced	0
psychosis	3
patients	0
in	0
the	0
allele	0
/	0
genotype	0
-	0
wise	0
analysis	0
.	0

Moreover	0
,	0
this	0
association	0
remained	0
significant	0
after	0
Bonferroni	0
correction	0
.	0

In	0
the	0
haplotype	0
-	0
wise	0
analysis	0
,	0
we	0
detected	0
an	0
association	0
between	0
two	0
markers	0
(	0
rs6693503	0
and	0
rs1805054	0
)	0
and	0
three	0
markers	0
(	0
rs6693503	0
,	0
rs1805054	0
and	0
rs4912138	0
)	0
in	0
HTR6	0
and	0
METH	1
-	0
induced	0
psychosis	3
patients	0
,	0
respectively	0
.	0

C0NCLUSI0N	0
:	0
HTR6	0
may	0
play	0
an	0
important	0
role	0
in	0
the	0
pathophysiology	0
of	0
METH	1
-	0
induced	0
psychosis	3
in	0
the	0
Japanese	0
population	0
.	0

Neural	0
correlates	0
of	0
S	1
-	2
ketamine	2
induced	0
psychosis	3
during	0
overt	0
continuous	0
verbal	0
fluency	0
.	0

The	0
glutamatergic	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
(	0
NMDA	1
)	0
receptor	0
has	0
been	0
implicated	0
in	0
the	0
pathophysiology	0
of	0
schizophrenia	3
.	0

Administered	0
to	0
healthy	0
volunteers	0
,	0
a	0
subanesthetic	0
dose	0
of	0
the	0
non	0
-	0
competitive	0
NMDA	1
receptor	0
antagonist	0
ketamine	1
leads	0
to	0
psychopathological	0
symptoms	0
similar	0
to	0
those	0
observed	0
in	0
schizophrenia	3
.	0

In	0
patients	0
with	0
schizophrenia	3
,	0
ketamine	1
exacerbates	0
the	0
core	0
symptoms	0
of	0
illness	0
,	0
supporting	0
the	0
hypothesis	0
of	0
a	0
glutamatergic	3
dysfunction	4
.	0

In	0
a	0
counterbalanced	0
,	0
placebo	0
-	0
controlled	0
,	0
double	0
-	0
blind	0
study	0
design	0
,	0
healthy	0
subjects	0
were	0
administered	0
a	0
continuous	0
subanesthetic	0
S	1
-	2
ketamine	2
infusion	0
while	0
differences	0
in	0
B0LD	0
responses	0
measured	0
with	0
fMRI	0
were	0
detected	0
.	0

During	0
the	0
scanning	0
period	0
,	0
subjects	0
performed	0
continuous	0
overt	0
verbal	0
fluency	0
tasks	0
(	0
phonological	0
,	0
lexical	0
and	0
semantic	0
)	0
.	0

Ketamine	1
-	0
induced	0
psychopathological	0
symptoms	0
were	0
assessed	0
with	0
the	0
Positive	0
and	0
Negative	0
Syndrome	0
Scale	0
(	0
PANSS	0
)	0
.	0

Ketamine	1
elicited	0
psychosis	3
like	0
psychopathology	0
.	0

Post	0
-	0
hoc	0
t	0
-	0
tests	0
revealed	0
significant	0
differences	0
between	0
placebo	0
and	0
ketamine	1
for	0
the	0
amounts	0
of	0
words	0
generated	0
during	0
lexical	0
and	0
semantic	0
verbal	0
fluency	0
,	0
while	0
the	0
phonological	0
domain	0
remained	0
unaffected	0
.	0

Ketamine	1
led	0
to	0
enhanced	0
cortical	0
activations	0
in	0
supramarginal	0
and	0
frontal	0
brain	0
regions	0
for	0
phonological	0
and	0
lexical	0
verbal	0
fluency	0
,	0
but	0
not	0
for	0
semantic	0
verbal	0
fluency	0
.	0

Ketamine	1
induces	0
activation	0
changes	0
in	0
healthy	0
subjects	0
similar	0
to	0
those	0
observed	0
in	0
patients	0
with	0
schizophrenia	3
,	0
particularly	0
in	0
frontal	0
and	0
temporal	0
brain	0
regions	0
.	0

0ur	0
results	0
provide	0
further	0
support	0
for	0
the	0
hypothesis	0
of	0
an	0
NMDA	1
receptor	0
dysfunction	0
in	0
the	0
pathophysiology	0
of	0
schizophrenia	3
.	0

Long	0
-	0
term	0
prognosis	0
for	0
transplant	0
-	0
free	0
survivors	0
of	0
paracetamol	1
-	0
induced	0
acute	3
liver	4
failure	4
.	0

BACKGR0UND	0
:	0
The	0
prognosis	0
for	0
transplant	0
-	0
free	0
survivors	0
of	0
paracetamol	1
-	0
induced	0
acute	3
liver	4
failure	4
remains	0
unknown	0
.	0

AIM	0
:	0
To	0
examine	0
whether	0
paracetamol	1
-	0
induced	0
acute	3
liver	4
failure	4
increases	0
long	0
-	0
term	0
mortality	0
.	0

METH0DS	0
:	0
We	0
followed	0
up	0
all	0
transplant	0
-	0
free	0
survivors	0
of	0
paracetamol	1
-	0
induced	0
acute	3
liver	4
injury	4
,	0
hospitalized	0
in	0
a	0
Danish	0
national	0
referral	0
centre	0
during	0
1984	0
-	0
2004	0
.	0

We	0
compared	0
age	0
-	0
specific	0
mortality	0
rates	0
from	0
1	0
year	0
post	0
-	0
discharge	0
through	0
2008	0
between	0
those	0
in	0
whom	0
the	0
liver	3
injury	4
led	0
to	0
an	0
acute	3
liver	4
failure	4
and	0
those	0
in	0
whom	0
it	0
did	0
not	0
.	0

RESULTS	0
:	0
We	0
included	0
641	0
patients	0
.	0

0n	0
average	0
,	0
age	0
-	0
specific	0
mortality	0
rates	0
were	0
slightly	0
higher	0
for	0
the	0
101	0
patients	0
whose	0
paracetamol	1
-	0
induced	0
liver	3
injury	4
had	0
caused	0
an	0
acute	3
liver	4
failure	4
(	0
adjusted	0
mortality	0
rate	0
ratio	0
=	0
1	0
.	0
70	0
,	0
95	0
%	0
CI	0
1	0
.	0
02	0
-	0
2	0
.	0
85	0
)	0
,	0
but	0
the	0
association	0
was	0
age	0
-	0
dependent	0
,	0
and	0
no	0
survivors	0
of	0
acute	3
liver	4
failure	4
died	0
of	0
liver	3
disease	4
,	0
whereas	0
suicides	0
were	0
frequent	0
in	0
both	0
groups	0
.	0

These	0
observations	0
speak	0
against	0
long	0
-	0
term	0
effects	0
of	0
acute	3
liver	4
failure	4
.	0

More	0
likely	0
,	0
the	0
elevated	0
mortality	0
rate	0
ratio	0
resulted	0
from	0
incomplete	0
adjustment	0
for	0
the	0
greater	0
prevalence	0
of	0
substance	3
abuse	4
among	0
survivors	0
of	0
acute	3
liver	4
failure	4
.	0

C0NCLUSI0NS	0
:	0
Paracetamol	1
-	0
induced	0
acute	3
liver	4
failure	4
did	0
not	0
affect	0
long	0
-	0
term	0
mortality	0
.	0

Clinical	0
follow	0
-	0
up	0
may	0
be	0
justified	0
by	0
the	0
cause	0
of	0
the	0
liver	3
failure	4
,	0
but	0
not	0
by	0
the	0
liver	3
failure	4
itself	0
.	0

In	0
vivo	0
characterization	0
of	0
a	0
dual	0
adenosine	1
A2A	2
/	2
A1	2
receptor	2
antagonist	2
in	0
animal	0
models	0
of	0
Parkinson	3
'	4
s	4
disease	4
.	0

The	0
in	0
vivo	0
characterization	0
of	0
a	0
dual	0
adenosine	1
A	2
(	2
2A	2
)	2
/	2
A	2
(	2
1	2
)	2
receptor	2
antagonist	2
in	0
several	0
animal	0
models	0
of	0
Parkinson	3
'	4
s	4
disease	4
is	0
described	0
.	0

Discovery	0
and	0
scale	0
-	0
up	0
syntheses	0
of	0
compound	0
1	0
are	0
described	0
in	0
detail	0
,	0
highlighting	0
optimization	0
steps	0
that	0
increased	0
the	0
overall	0
yield	0
of	0
1	0
from	0
10	0
.	0
0	0
%	0
to	0
30	0
.	0
5	0
%	0
.	0

Compound	0
1	0
is	0
a	0
potent	0
A	0
(	0
2A	0
)	0
/	0
A	0
(	0
1	0
)	0
receptor	0
antagonist	0
in	0
vitro	0
(	0
A	0
(	0
2A	0
)	0
K	0
(	0
i	0
)	0
=	0
4	0
.	0
1	0
nM	0
;	0
A	0
(	0
1	0
)	0
K	0
(	0
i	0
)	0
=	0
17	0
.	0
0	0
nM	0
)	0
that	0
has	0
excellent	0
activity	0
,	0
after	0
oral	0
administration	0
,	0
across	0
a	0
number	0
of	0
animal	0
models	0
of	0
Parkinson	3
'	4
s	4
disease	4
including	0
mouse	0
and	0
rat	0
models	0
of	0
haloperidol	1
-	0
induced	0
catalepsy	3
,	0
mouse	0
model	0
of	0
reserpine	1
-	0
induced	0
akinesia	3
,	0
rat	0
6	1
-	2
hydroxydopamine	2
(	0
6	1
-	2
0HDA	2
)	0
lesion	0
model	0
of	0
drug	0
-	0
induced	0
rotation	0
,	0
and	0
MPTP	1
-	0
treated	0
non	0
-	0
human	0
primate	0
model	0
.	0

Effects	0
of	0
the	0
hippocampal	0
deep	0
brain	0
stimulation	0
on	0
cortical	0
epileptic	3
discharges	0
in	0
penicillin	1
-	0
induced	0
epilepsy	3
model	0
in	0
rats	0
.	0

AIM	0
:	0
Experimental	0
and	0
clinical	0
studies	0
have	0
revealed	0
that	0
hippocampal	0
DBS	0
can	0
control	0
epileptic	3
activity	0
,	0
but	0
the	0
mechanism	0
of	0
action	0
is	0
obscure	0
and	0
optimal	0
stimulation	0
parameters	0
are	0
not	0
clearly	0
defined	0
.	0

The	0
aim	0
was	0
to	0
evaluate	0
the	0
effects	0
of	0
high	0
frequency	0
hippocampal	0
stimulation	0
on	0
cortical	0
epileptic	3
activity	0
in	0
penicillin	1
-	0
induced	0
epilepsy	3
model	0
.	0

MATERIAL	0
AND	0
METH0DS	0
:	0
Twenty	0
-	0
five	0
Sprague	0
-	0
Dawley	0
rats	0
were	0
implanted	0
DBS	0
electrodes	0
.	0

In	0
group	0
-	0
1	0
(	0
n	0
=	0
10	0
)	0
hippocampal	0
DBS	0
was	0
off	0
and	0
in	0
the	0
group	0
-	0
2	0
(	0
n	0
=	0
10	0
)	0
hippocampal	0
DBS	0
was	0
on	0
(	0
185	0
Hz	0
,	0
0	0
.	0
5V	0
,	0
1V	0
,	0
2V	0
,	0
and	0
5V	0
for	0
60	0
sec	0
)	0
following	0
penicillin	1
G	2
injection	0
intracortically	0
.	0

In	0
the	0
control	0
group	0
hippocampal	0
DBS	0
was	0
on	0
following	0
8	0
l	0
saline	0
injection	0
intracortically	0
.	0

EEG	0
recordings	0
were	0
obtained	0
before	0
and	0
15	0
minutes	0
following	0
penicillin	1
-	2
G	2
injection	0
,	0
and	0
at	0
10th	0
minutes	0
following	0
each	0
stimulus	0
for	0
analysis	0
in	0
terms	0
of	0
frequency	0
,	0
amplitude	0
,	0
and	0
power	0
spectrum	0
.	0

RESULTS	0
:	0
High	0
frequency	0
hippocampal	0
DBS	0
suppressed	0
the	0
acute	0
penicillin	1
-	0
induced	0
cortical	0
epileptic	3
activity	0
independent	0
from	0
stimulus	0
intensity	0
.	0

In	0
the	0
control	0
group	0
,	0
hippocampal	0
stimulation	0
alone	0
lead	0
only	0
to	0
diffuse	0
slowing	0
of	0
cerebral	0
bioelectrical	0
activity	0
at	0
5V	0
stimulation	0
.	0

C0NCLUSI0N	0
:	0
0ur	0
results	0
revealed	0
that	0
continuous	0
high	0
frequency	0
stimulation	0
of	0
the	0
hippocampus	0
suppressed	0
acute	0
cortical	0
epileptic	3
activity	0
effectively	0
without	0
causing	0
secondary	0
epileptic	3
discharges	0
.	0

These	0
results	0
are	0
important	0
in	0
terms	0
of	0
defining	0
the	0
optimal	0
parameters	0
of	0
hippocampal	0
DBS	0
in	0
patients	0
with	0
epilepsy	3
.	0

CCNU	1
(	0
lomustine	1
)	0
toxicity	3
in	0
dogs	0
:	0
a	0
retrospective	0
study	0
(	0
2002	0
-	0
07	0
)	0
.	0

0BJECTIVE	0
:	0
To	0
describe	0
the	0
incidence	0
of	0
haematological	3
,	4
renal	4
,	4
hepatic	4
and	4
gastrointestinal	4
toxicities	4
in	0
tumour	0
-	0
bearing	0
dogs	0
receiving	0
1	1
-	2
(	2
2	2
-	2
chloroethyl	2
)	2
-	2
3	2
-	2
cyclohexyl	2
-	2
1	2
-	2
nitrosourea	2
(	0
CCNU	1
)	0
.	0

DESIGN	0
:	0
The	0
medical	0
records	0
of	0
206	0
dogs	0
that	0
were	0
treated	0
with	0
CCNU	1
at	0
the	0
Melbourne	0
Veterinary	0
Specialist	0
Centre	0
between	0
February	0
2002	0
and	0
December	0
2007	0
were	0
retrospectively	0
evaluated	0
.	0

RESULTS	0
:	0
0f	0
the	0
206	0
dogs	0
treated	0
with	0
CCNU	1
,	0
185	0
met	0
the	0
inclusion	0
criteria	0
for	0
at	0
least	0
one	0
class	0
of	0
toxicity	3
.	0

CCNU	1
was	0
used	0
most	0
commonly	0
in	0
the	0
treatment	0
of	0
lymphoma	3
,	0
mast	3
cell	4
tumour	4
,	0
brain	3
tumour	4
,	0
histiocytic	3
tumours	4
and	0
epitheliotropic	3
lymphoma	4
.	0

Throughout	0
treatment	0
,	0
56	0
.	0
9	0
%	0
of	0
dogs	0
experienced	0
neutropenia	3
,	0
34	0
.	0
2	0
%	0
experienced	0
anaemia	3
and	0
14	0
.	0
2	0
%	0
experienced	0
thrombocytopenia	3
.	0

Gastrointestinal	3
toxicosis	4
was	0
detected	0
in	0
37	0
.	0
8	0
%	0
of	0
dogs	0
,	0
the	0
most	0
common	0
sign	0
of	0
which	0
was	0
vomiting	3
(	0
24	0
.	0
3	0
%	0
)	0
.	0

Potential	0
renal	0
toxicity	3
and	0
elevated	0
alanine	1
transaminase	0
(	0
ALT	0
)	0
concentration	0
were	0
reported	0
in	0
12	0
.	0
2	0
%	0
and	0
48	0
.	0
8	0
%	0
of	0
dogs	0
,	0
respectively	0
.	0

The	0
incidence	0
of	0
hepatic	3
failure	4
was	0
1	0
.	0
2	0
%	0
.	0

C0NCLUSI0NS	0
:	0
CCNU	1
-	0
associated	0
toxicity	3
in	0
dogs	0
is	0
common	0
,	0
but	0
is	0
usually	0
not	0
life	0
threatening	0
.	0

Central	0
vein	3
thrombosis	4
and	0
topical	0
dipivalyl	1
epinephrine	2
.	0

A	0
report	0
is	0
given	0
on	0
an	0
83	0
-	0
year	0
-	0
old	0
female	0
who	0
acquired	0
central	0
vein	3
thrombosis	4
in	0
her	0
seeing	0
eye	0
one	0
day	0
after	0
having	0
started	0
topical	0
medication	0
with	0
dipivalyl	1
epinephrine	2
for	0
advanced	0
glaucoma	3
discovered	0
in	0
the	0
other	0
eye	0
.	0

From	0
present	0
knowledge	0
about	0
the	0
effects	0
of	0
adrenergic	0
eye	0
drops	0
on	0
ocular	0
blood	0
circulation	0
,	0
it	0
is	0
difficult	0
to	0
suggest	0
an	0
association	0
between	0
the	0
two	0
events	0
,	0
which	0
may	0
be	0
coincidental	0
only	0
.	0

Benzylacyclouridine	1
reverses	0
azidothymidine	1
-	0
induced	0
marrow	3
suppression	4
without	0
impairment	0
of	0
anti	0
-	0
human	0
immunodeficiency	3
virus	0
activity	0
.	0

Increased	0
extracellular	0
concentrations	0
of	0
uridine	1
(	0
Urd	1
)	0
have	0
been	0
reported	0
to	0
reduce	0
,	0
in	0
vitro	0
,	0
azidothymidine	1
(	0
AZT	1
)	0
-	0
induced	0
inhibition	0
of	0
human	0
granulocyte	0
-	0
macrophage	0
progenitor	0
cells	0
without	0
impairment	0
of	0
its	0
antihuman	0
immunodeficiency	3
virus	0
(	0
HIV	0
)	0
activity	0
.	0

Because	0
of	0
the	0
clinical	0
toxicities	3
associated	0
with	0
chronic	0
Urd	1
administration	0
,	0
the	0
ability	0
of	0
benzylacyclouridine	1
(	0
BAU	1
)	0
to	0
effect	0
,	0
in	0
vivo	0
,	0
AZT	1
-	0
induced	0
anemia	3
and	0
leukopenia	3
was	0
assessed	0
.	0

This	0
agent	0
inhibits	0
Urd	1
catabolism	0
and	0
,	0
in	0
vivo	0
,	0
increases	0
the	0
plasma	0
concentration	0
of	0
Urd	1
in	0
a	0
dose	0
-	0
dependent	0
manner	0
,	0
without	0
Urd	1
-	0
related	0
toxicity	3
.	0

In	0
mice	0
rendered	0
anemic	3
and	0
leukopenic	3
by	0
the	0
administration	0
of	0
AZT	1
for	0
28	0
days	0
in	0
drinking	0
water	0
(	0
1	0
.	0
5	0
mg	0
/	0
mL	0
)	0
,	0
the	0
continued	0
administration	0
of	0
AZT	1
plus	0
daily	0
BAU	1
(	0
300	0
mg	0
/	0
kg	0
,	0
orally	0
)	0
partially	0
reversed	0
AZT	1
-	0
induced	0
anemia	3
and	0
leukopenia	3
(	0
P	0
less	0
than	0
.	0
05	0
)	0
,	0
increased	0
peripheral	0
reticulocytes	0
(	0
to	0
4	0
.	0
9	0
%	0
,	0
P	0
less	0
than	0
.	0
01	0
)	0
,	0
increased	0
cellularity	0
in	0
the	0
marrow	0
,	0
and	0
improved	0
megaloblastosis	3
.	0

When	0
coadministered	0
with	0
AZT	1
from	0
the	0
onset	0
of	0
drug	0
administration	0
,	0
BAU	1
reduced	0
AZT	1
-	0
induced	0
marrow	3
toxicity	4
.	0

In	0
vitro	0
,	0
at	0
a	0
concentration	0
of	0
100	0
mumol	0
/	0
L	0
,	0
BAU	1
possesses	0
minimal	0
anti	0
-	0
HIV	0
activity	0
and	0
has	0
no	0
effect	0
on	0
the	0
ability	0
of	0
AZT	1
to	0
reverse	0
the	0
HIV	0
-	0
induced	0
cytopathic	0
effect	0
in	0
MT4	0
cells	0
.	0

The	0
clinical	0
and	0
biochemical	0
implications	0
of	0
these	0
findings	0
are	0
discussed	0
.	0

Lethal	0
anuria	3
complicating	0
high	0
dose	0
ifosfamide	1
chemotherapy	0
in	0
a	0
breast	3
cancer	4
patient	0
with	0
an	0
impaired	3
renal	4
function	4
.	0

A	0
sixty	0
-	0
year	0
-	0
old	0
woman	0
with	0
advanced	0
breast	3
cancer	4
,	0
previously	0
treated	0
with	0
cisplatin	1
,	0
developed	0
an	0
irreversible	0
lethal	0
renal	3
failure	4
with	0
anuria	3
,	0
the	0
day	0
after	0
5	0
g	0
/	0
m2	0
bolus	0
ifosfamide	1
.	0

Postrenal	3
failure	4
was	0
excluded	0
by	0
echography	0
.	0

A	0
prerenal	0
component	0
could	0
have	0
contributed	0
to	0
renal	3
failure	4
because	0
of	0
a	0
transient	0
hypotension	3
,	0
due	0
to	0
an	0
increasing	0
ascitis	0
,	0
occurring	0
just	0
before	0
anuria	3
.	0

However	0
,	0
correction	0
of	0
the	0
hemodynamic	0
parameters	0
did	0
not	0
improve	0
renal	0
function	0
.	0

Ifosfamide	1
is	0
a	0
known	0
nephrotoxic	3
drug	0
with	0
demonstrated	0
tubulopathies	3
.	0

We	0
strongly	0
suspect	0
that	0
this	0
lethal	0
anuria	3
was	0
mainly	0
due	0
to	0
ifosfamide	1
,	0
occurring	0
in	0
a	0
patient	0
having	0
received	0
previous	0
cisplatin	1
chemotherapy	0
and	0
with	0
poor	0
kidney	0
perfusion	0
due	0
to	0
transient	0
hypotension	3
.	0

We	0
recommend	0
careful	0
use	0
of	0
ifosfamide	1
in	0
patients	0
pretreated	0
with	0
nephrotoxic	3
chemotherapy	0
and	0
inadequate	0
renal	0
perfusion	0
.	0

Nociceptive	0
effects	0
induced	0
by	0
intrathecal	0
administration	0
of	0
prostaglandin	1
D2	2
,	2
E2	2
,	2
or	2
F2	2
alpha	2
to	0
conscious	0
mice	0
.	0

The	0
effects	0
of	0
intrathecal	0
administration	0
of	0
prostaglandins	1
on	0
pain	3
responses	0
in	0
conscious	0
mice	0
were	0
evaluated	0
by	0
using	0
hot	0
plate	0
and	0
acetic	1
acid	2
writhing	0
tests	0
.	0

Prostaglandin	1
D2	2
(	0
0	0
.	0
5	0
-	0
3	0
ng	0
/	0
mouse	0
)	0
had	0
a	0
hyperalgesic	3
action	0
on	0
the	0
response	0
to	0
a	0
hot	0
plate	0
during	0
a	0
3	0
-	0
60	0
min	0
period	0
after	0
injection	0
.	0

Prostaglandin	1
E2	2
showed	0
a	0
hyperalgesic	3
effect	0
at	0
doses	0
of	0
1	0
pg	1
to	0
10	0
ng	0
/	0
mouse	0
,	0
but	0
the	0
effect	0
lasted	0
shorter	0
(	0
3	0
-	0
30	0
min	0
)	0
than	0
that	0
of	0
prostaglandin	1
D2	2
.	0

Similar	0
results	0
were	0
obtained	0
by	0
acetic	1
acid	2
writhing	0
tests	0
.	0

The	0
hyperalgesic	3
effect	0
of	0
prostaglandin	1
D2	2
was	0
blocked	0
by	0
simultaneous	0
injection	0
of	0
a	0
substance	0
P	0
antagonist	0
(	0
greater	0
than	0
or	0
equal	0
to	0
100	0
ng	0
)	0
but	0
not	0
by	0
AH6809	1
,	0
a	0
prostanoid	0
EP1	0
-	0
receptor	0
antagonist	0
.	0

Conversely	0
,	0
prostaglandin	1
E2	2
-	0
induced	0
hyperalgesia	3
was	0
blocked	0
by	0
AH6809	1
(	0
greater	0
than	0
or	0
equal	0
to	0
500	0
ng	0
)	0
but	0
not	0
by	0
the	0
substance	0
P	0
antagonist	0
.	0

Prostaglandin	1
F2	2
alpha	2
had	0
little	0
effect	0
on	0
pain	3
responses	0
.	0

These	0
results	0
demonstrate	0
that	0
both	0
prostaglandin	1
D2	2
and	0
prostaglandin	1
E2	2
exert	0
hyperalgesia	3
in	0
the	0
spinal	0
cord	0
,	0
but	0
in	0
different	0
ways	0
.	0

D	1
-	2
penicillamine	2
in	0
the	0
treatment	0
of	0
localized	3
scleroderma	4
.	0

Localized	3
scleroderma	4
has	0
no	0
recognized	0
internal	0
organ	0
involvement	0
but	0
may	0
be	0
disfiguring	0
and	0
disabling	0
when	0
the	0
cutaneous	0
lesions	0
are	0
extensive	0
or	0
affect	0
children	0
.	0

There	0
is	0
no	0
accepted	0
or	0
proven	0
treatment	0
for	0
localized	3
scleroderma	4
.	0

Case	0
reports	0
of	0
11	0
patients	0
with	0
severe	0
,	0
extensive	0
localized	3
scleroderma	4
who	0
were	0
treated	0
with	0
D	1
-	2
penicillamine	2
are	0
summarized	0
in	0
this	0
article	0
.	0

This	0
drug	0
was	0
judged	0
to	0
have	0
a	0
favorable	0
effect	0
on	0
the	0
disease	0
course	0
in	0
7	0
(	0
64	0
%	0
)	0
of	0
11	0
patients	0
.	0

Improvement	0
began	0
within	0
3	0
to	0
6	0
months	0
and	0
consisted	0
of	0
cessation	0
of	0
active	0
cutaneous	0
lesions	0
in	0
all	0
7	0
patients	0
,	0
skin	0
softening	0
in	0
5	0
,	0
and	0
more	0
normal	0
growth	0
of	0
the	0
affected	0
limb	0
in	0
2	0
of	0
3	0
children	0
.	0

Joint	0
stiffness	0
and	0
contractures	3
also	0
improved	0
.	0

The	0
dose	0
of	0
D	1
-	2
penicillamine	2
associated	0
with	0
a	0
favorable	0
response	0
was	0
as	0
low	0
as	0
2	0
to	0
5	0
mg	0
/	0
kg	0
per	0
day	0
given	0
over	0
a	0
period	0
ranging	0
from	0
15	0
to	0
53	0
months	0
.	0

D	1
-	2
Penicillamine	2
caused	0
nephrotic	3
syndrome	4
in	0
1	0
patient	0
and	0
milder	0
reversible	0
proteinuria	3
in	0
3	0
other	0
patients	0
;	0
none	0
developed	0
renal	3
insufficiency	4
.	0

These	0
data	0
suggest	0
that	0
D	1
-	2
penicillamine	2
may	0
be	0
effective	0
in	0
severe	0
cases	0
of	0
localized	3
scleroderma	4
.	0

Cerebral	3
sinus	4
thrombosis	4
as	0
a	0
potential	0
hazard	0
of	0
antifibrinolytic	0
treatment	0
in	0
menorrhagia	3
.	0

We	0
describe	0
a	0
42	0
-	0
year	0
-	0
old	0
woman	0
who	0
developed	0
superior	0
sagittal	3
and	4
left	4
transverse	4
sinus	4
thrombosis	4
associated	0
with	0
prolonged	0
epsilon	1
-	2
aminocaproic	2
acid	2
therapy	0
for	0
menorrhagia	3
.	0

This	0
antifibrinolytic	0
agent	0
has	0
been	0
used	0
in	0
women	0
with	0
menorrhagia	3
to	0
promote	0
clotting	0
and	0
reduce	0
blood	3
loss	4
.	0

Although	0
increased	0
risk	0
of	0
thromboembolic	3
disease	4
has	0
been	0
reported	0
during	0
treatment	0
with	0
epsilon	1
-	2
aminocaproic	2
acid	2
,	0
cerebral	3
sinus	4
thrombosis	4
has	0
not	0
been	0
previously	0
described	0
.	0

Careful	0
use	0
of	0
epsilon	1
-	2
aminocaproic	2
acid	2
therapy	0
is	0
recommended	0
.	0

Seizure	3
activity	0
with	0
imipenem	1
therapy	0
:	0
incidence	0
and	0
risk	0
factors	0
.	0

Two	0
elderly	0
patients	0
with	0
a	0
history	0
of	0
either	0
cerebral	3
vascular	4
accident	4
(	0
CVA	3
)	0
or	0
head	3
trauma	4
and	0
no	0
evidence	0
of	0
renal	3
disease	4
developed	0
seizures	3
while	0
receiving	0
maximum	0
doses	0
of	0
imipenem	1
/	2
cilastatin	2
.	0

Neither	0
patient	0
had	0
reported	0
previous	0
seizures	3
or	0
seizure	3
-	0
like	0
activity	0
nor	0
was	0
receiving	0
anticonvulsant	0
agents	0
.	0

All	0
seizures	3
were	0
controlled	0
with	0
therapeutic	0
doses	0
of	0
phenytoin	1
.	0

Both	0
patients	0
had	0
received	0
maximum	0
doses	0
of	0
other	0
beta	1
-	2
lactam	2
antibiotics	0
without	0
evidence	0
of	0
seizure	3
activity	0
.	0

Midline	0
B3	0
serotonin	1
nerves	0
in	0
rat	0
medulla	0
are	0
involved	0
in	0
hypotensive	3
effect	0
of	0
methyldopa	1
.	0

Previous	0
experiments	0
in	0
this	0
laboratory	0
have	0
shown	0
that	0
microinjection	0
of	0
methyldopa	1
onto	0
the	0
ventrolateral	0
cells	0
of	0
the	0
B3	0
serotonin	1
neurons	0
in	0
the	0
medulla	0
elicits	0
a	0
hypotensive	3
response	0
mediated	0
by	0
a	0
projection	0
descending	0
into	0
the	0
spinal	0
cord	0
.	0

The	0
present	0
experiments	0
were	0
designed	0
to	0
investigate	0
the	0
role	0
of	0
the	0
midline	0
cells	0
of	0
the	0
B3	0
serotonin	1
neurons	0
in	0
the	0
medulla	0
,	0
coinciding	0
with	0
the	0
raphe	0
magnus	0
.	0

In	0
spontaneously	0
hypertensive	3
,	0
stroke	3
-	0
prone	0
rats	0
,	0
microinjection	0
of	0
methyldopa	1
into	0
the	0
area	0
of	0
the	0
midline	0
B3	0
serotonin	1
cell	0
group	0
in	0
the	0
ventral	0
medulla	0
caused	0
a	0
potent	0
hypotension	3
of	0
30	0
-	0
40	0
mm	0
Hg	0
,	0
which	0
was	0
maximal	0
2	0
-	0
3	0
h	0
after	0
administration	0
and	0
was	0
abolished	0
by	0
the	0
serotonin	1
neurotoxin	0
5	1
,	2
7	2
-	2
dihydroxytryptamine	2
(	0
5	1
,	2
7	2
-	2
DHT	2
)	0
injected	0
intracerebroventricularly	0
.	0

However	0
,	0
intraspinal	0
injection	0
of	0
5	1
,	2
7	2
-	2
DHT	2
to	0
produce	0
a	0
more	0
selective	0
lesion	0
of	0
only	0
descending	0
serotonin	1
projections	0
in	0
the	0
spinal	0
cord	0
did	0
not	0
affect	0
this	0
hypotension	3
.	0

Further	0
,	0
5	1
,	2
7	2
-	2
DHT	2
lesion	0
of	0
serotonin	1
nerves	0
travelling	0
in	0
the	0
median	0
forebrain	0
bundle	0
,	0
one	0
of	0
the	0
main	0
ascending	0
pathways	0
from	0
the	0
B3	0
serotonin	1
cells	0
,	0
did	0
not	0
affect	0
the	0
fall	0
in	0
blood	0
pressure	0
associated	0
with	0
a	0
midline	0
B3	0
serotonin	1
methyldopa	1
injection	0
.	0

It	0
is	0
concluded	0
therefore	0
that	0
,	0
unlike	0
the	0
ventrolateral	0
B3	0
cells	0
which	0
mediate	0
a	0
methyldopa	1
-	0
induced	0
hypotension	3
via	0
descending	0
projections	0
,	0
the	0
midline	0
serotonin	1
B3	0
cells	0
in	0
the	0
medulla	0
contribute	0
to	0
the	0
hypotensive	3
action	0
of	0
methyldopa	1
,	0
either	0
by	0
way	0
of	0
an	0
ascending	0
projection	0
which	0
does	0
not	0
pass	0
through	0
the	0
median	0
forebrain	0
bundle	0
,	0
or	0
through	0
a	0
projection	0
restricted	0
to	0
the	0
caudal	0
brainstem	0
.	0

Antiarrhythmic	0
plasma	0
concentrations	0
of	0
cibenzoline	1
on	0
canine	0
ventricular	3
arrhythmias	4
.	0

Using	0
two	0
-	0
stage	0
coronary	0
ligation	0
-	0
,	0
digitalis	1
-	0
,	0
and	0
adrenaline	1
-	0
induced	0
canine	0
ventricular	3
arrhythmias	4
,	0
antiarrhythmic	0
effects	0
of	0
cibenzoline	1
were	0
examined	0
and	0
the	0
minimum	0
effective	0
plasma	0
concentration	0
for	0
each	0
arrhythmia	3
model	0
was	0
determined	0
.	0

Cibenzoline	1
suppressed	0
all	0
the	0
arrhythmias	3
,	0
and	0
the	0
minimum	0
effective	0
plasma	0
concentrations	0
for	0
arrhythmias	3
induced	0
by	0
24	0
-	0
h	0
coronary	0
ligation	0
,	0
48	0
-	0
h	0
coronary	0
ligation	0
,	0
digitalis	1
,	0
and	0
adrenaline	1
were	0
1	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
9	0
(	0
by	0
8	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
,	0
1	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
5	0
(	0
by	0
8	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
,	0
0	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
2	0
(	0
by	0
2	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
,	0
and	0
3	0
.	0
5	0
+	0
/	0
-	0
1	0
.	0
3	0
(	0
by	0
5	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
micrograms	0
/	0
ml	0
,	0
respectively	0
(	0
mean	0
+	0
/	0
-	0
SDM	0
,	0
n	0
=	0
6	0
-	0
7	0
)	0
.	0

The	0
concentration	0
for	0
adrenaline	1
-	0
induced	0
arrhythmia	3
was	0
significantly	0
higher	0
than	0
those	0
for	0
the	0
other	0
types	0
of	0
arrhythmias	3
.	0

This	0
pharmacological	0
profile	0
is	0
similar	0
to	0
those	0
of	0
mexiletine	1
and	0
tocainide	1
,	0
and	0
all	0
three	0
drugs	0
have	0
central	0
nervous	0
system	0
(	0
CNS	0
)	0
stimulant	0
action	0
.	0

Because	0
cibenzoline	1
had	0
only	0
weak	0
hypotensive	3
and	0
sinus	0
node	0
depressive	3
effects	0
and	0
was	0
found	0
to	0
be	0
orally	0
active	0
when	0
given	0
to	0
coronary	0
ligation	0
arrhythmia	3
dogs	0
,	0
its	0
clinical	0
usefulness	0
is	0
expected	0
.	0

Continuous	0
ambulatory	0
ECG	0
monitoring	0
during	0
fluorouracil	1
therapy	0
:	0
a	0
prospective	0
study	0
.	0

Although	0
there	0
have	0
been	0
anecdotal	0
reports	0
of	0
cardiac	3
toxicity	4
associated	0
with	0
fluorouracil	1
(	0
5	1
-	2
FU	2
)	0
therapy	0
,	0
this	0
phenomenon	0
has	0
not	0
been	0
studied	0
in	0
a	0
systematic	0
fashion	0
.	0

We	0
prospectively	0
performed	0
continuous	0
ambulatory	0
ECG	0
monitoring	0
on	0
25	0
patients	0
undergoing	0
5	1
-	2
FU	2
infusion	0
for	0
treatment	0
of	0
solid	0
tumors	3
in	0
order	0
to	0
assess	0
the	0
incidence	0
of	0
ischemic	3
ST	0
changes	0
.	0

Patients	0
were	0
monitored	0
for	0
23	0
+	0
/	0
-	0
4	0
hours	0
before	0
5	1
-	2
FU	2
infusion	0
,	0
and	0
98	0
+	0
/	0
-	0
9	0
hours	0
during	0
5	1
-	2
FU	2
infusion	0
.	0

Anginal	3
episodes	0
were	0
rare	0
:	0
only	0
one	0
patient	0
had	0
angina	3
(	0
during	0
5	1
-	2
FU	2
infusion	0
)	0
.	0

However	0
,	0
asymptomatic	0
ST	0
changes	0
(	0
greater	0
than	0
or	0
equal	0
to	0
1	0
mm	0
ST	0
deviation	0
)	0
were	0
common	0
:	0
six	0
of	0
25	0
patients	0
(	0
24	0
%	0
)	0
had	0
ST	0
changes	0
before	0
5	1
-	2
FU	2
infusion	0
v	0
17	0
(	0
68	0
%	0
)	0
during	0
5	1
-	2
FU	2
infusion	0
(	0
P	0
less	0
than	0
.	0
002	0
)	0
.	0

The	0
incidence	0
of	0
ischemic	3
episodes	0
per	0
patient	0
per	0
hour	0
was	0
0	0
.	0
05	0
+	0
/	0
-	0
0	0
.	0
02	0
prior	0
to	0
5	1
-	2
FU	2
infusion	0
v	0
0	0
.	0
13	0
+	0
/	0
-	0
0	0
.	0
03	0
during	0
5	1
-	2
FU	2
infusion	0
(	0
P	0
less	0
than	0
.	0
001	0
)	0
;	0
the	0
duration	0
of	0
ECG	0
changes	0
was	0
0	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
3	0
minutes	0
per	0
patient	0
per	0
hour	0
before	0
5	1
-	2
FU	2
v	0
1	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
5	0
minutes	0
per	0
patient	0
per	0
hour	0
during	0
5	1
-	2
FU	2
(	0
P	0
less	0
than	0
.	0
01	0
)	0
.	0

ECG	0
changes	0
were	0
more	0
common	0
among	0
patients	0
with	0
known	0
coronary	3
artery	4
disease	4
.	0

There	0
were	0
two	0
cases	0
of	0
sudden	3
death	4
,	0
both	0
of	0
which	0
occurred	0
at	0
the	0
end	0
of	0
the	0
chemotherapy	0
course	0
.	0

We	0
conclude	0
that	0
5	1
-	2
FU	2
infusion	0
is	0
associated	0
with	0
a	0
significant	0
increase	0
in	0
silent	0
ST	0
segment	0
deviation	0
suggestive	0
of	0
ischemia	3
,	0
particularly	0
among	0
patients	0
with	0
coronary	3
artery	4
disease	4
.	0

The	0
mechanism	0
and	0
clinical	0
significance	0
of	0
these	0
ECG	0
changes	0
remain	0
to	0
be	0
determined	0
.	0

Nature	0
,	0
time	0
course	0
and	0
dose	0
dependence	0
of	0
zidovudine	1
-	0
related	0
side	0
effects	0
:	0
results	0
from	0
the	0
Multicenter	0
Canadian	0
Azidothymidine	1
Trial	0
.	0

To	0
characterize	0
the	0
nature	0
,	0
time	0
course	0
and	0
dose	0
dependency	0
of	0
zidovudine	1
-	0
related	0
side	0
effects	0
,	0
we	0
undertook	0
a	0
multicenter	0
,	0
prospective	0
,	0
dose	0
-	0
range	0
finding	0
study	0
.	0

0ur	0
study	0
group	0
consisted	0
of	0
74	0
HIV	0
-	0
positive	0
homosexual	0
men	0
belonging	0
to	0
groups	0
II	0
B	0
,	0
III	0
and	0
IV	0
C2	0
from	0
the	0
Centers	0
for	0
Disease	0
Control	0
(	0
CDC	0
)	0
classification	0
of	0
HIV	3
disease	4
.	0

Following	0
a	0
3	0
-	0
week	0
observation	0
period	0
,	0
volunteers	0
were	0
treated	0
with	0
zidovudine	1
600	0
mg	0
/	0
day	0
for	0
18	0
weeks	0
,	0
900	0
mg	0
/	0
day	0
for	0
9	0
weeks	0
and	0
1200	0
mg	0
/	0
day	0
for	0
9	0
weeks	0
,	0
followed	0
by	0
a	0
washout	0
period	0
of	0
6	0
weeks	0
after	0
which	0
they	0
were	0
re	0
-	0
started	0
on	0
1200	0
mg	0
/	0
day	0
or	0
the	0
highest	0
tolerated	0
dose	0
at	0
8	0
-	0
hourly	0
intervals	0
.	0

Subjects	0
were	0
randomly	0
assigned	0
to	0
4	0
-	0
hourly	0
or	0
8	0
-	0
hourly	0
regimens	0
within	0
CDC	0
groups	0
while	0
taking	0
600	0
and	0
1200	0
mg	0
/	0
day	0
.	0

Clinical	0
and	0
laboratory	0
evaluations	0
were	0
performed	0
at	0
3	0
-	0
week	0
intervals	0
.	0

Symptomatic	0
adverse	0
effects	0
were	0
present	0
in	0
96	0
%	0
of	0
subjects	0
,	0
most	0
commonly	0
nausea	3
(	0
64	0
%	0
)	0
,	0
fatigue	3
(	0
55	0
%	0
)	0
and	0
headache	3
(	0
49	0
%	0
)	0
.	0

These	0
were	0
generally	0
self	0
-	0
limited	0
,	0
reappearing	0
briefly	0
at	0
each	0
dose	0
increment	0
.	0

A	0
decrease	0
in	0
hemoglobin	0
occurred	0
shortly	0
after	0
initiation	0
of	0
therapy	0
.	0

This	0
was	0
not	0
dose	0
dependent	0
and	0
reversed	0
rapidly	0
upon	0
discontinuation	0
of	0
treatment	0
.	0

A	0
red	0
blood	0
cell	0
count	0
decrease	0
,	0
a	0
mean	0
cell	0
volume	0
increase	0
and	0
a	0
granulocyte	0
count	0
decrease	0
developed	0
early	0
in	0
a	0
dose	0
-	0
independent	0
fashion	0
,	0
reverting	0
at	0
least	0
partially	0
during	0
the	0
washout	0
phase	0
.	0

The	0
decrease	0
in	0
reticulocyte	0
count	0
was	0
dose	0
related	0
between	0
600	0
and	0
900	0
mg	0
/	0
day	0
with	0
no	0
further	0
change	0
when	0
the	0
dose	0
was	0
escalated	0
to	0
1200	0
mg	0
/	0
day	0
.	0

Bone	0
marrow	0
changes	0
occurred	0
rapidly	0
as	0
demonstrated	0
by	0
megaloblastosis	3
in	0
95	0
%	0
of	0
65	0
specimens	0
at	0
week	0
18	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

National	0
project	0
on	0
the	0
prevention	0
of	0
mother	0
-	0
to	0
-	0
infant	0
infection	3
by	4
hepatitis	4
B	4
virus	4
in	0
Japan	0
.	0

In	0
Japan	0
,	0
a	0
nationwide	0
prevention	0
program	0
against	0
mother	0
-	0
to	0
-	0
infant	0
infection	3
by	4
hepatitis	4
B	4
virus	4
(	0
HBV	0
)	0
started	0
in	0
1985	0
.	0

This	0
program	0
consists	0
of	0
double	0
screenings	0
of	0
pregnant	0
women	0
and	0
prophylactic	0
treatment	0
to	0
the	0
infants	0
born	0
to	0
both	0
hepatitis	1
B	2
surface	2
antigen	2
(	0
HBsAg	1
)	0
and	0
hepatitis	1
B	2
e	2
antigen	2
(	0
HBeAg	1
)	0
positive	0
mothers	0
.	0

These	0
infants	0
are	0
treated	0
with	0
two	0
injections	0
of	0
hepatitis	3
B	4
immune	0
globulin	0
(	0
HBIG	0
)	0
and	0
at	0
least	0
three	0
injections	0
of	0
plasma	0
derived	0
hepatitis	1
B	2
vaccine	2
.	0

We	0
sent	0
questionnaires	0
about	0
the	0
numbers	0
of	0
each	0
procedure	0
or	0
examination	0
during	0
nine	0
months	0
of	0
investigation	0
period	0
to	0
each	0
local	0
government	0
in	0
1986	0
and	0
1987	0
.	0

93	0
.	0
4	0
%	0
pregnant	0
women	0
had	0
the	0
chance	0
to	0
be	0
examined	0
for	0
HBsAg	1
,	0
and	0
the	0
positive	0
rate	0
was	0
1	0
.	0
4	0
to	0
1	0
.	0
5	0
%	0
.	0

The	0
HBeAg	1
positive	0
rate	0
in	0
HBsAg	1
positive	0
was	0
23	0
to	0
26	0
%	0
.	0

The	0
HBsAg	1
positive	0
rate	0
in	0
neonates	0
and	0
in	0
infants	0
before	0
two	0
months	0
were	0
3	0
%	0
and	0
2	0
%	0
respectively	0
.	0

Some	0
problems	0
may	0
arise	0
,	0
because	0
27	0
to	0
30	0
%	0
of	0
infants	0
need	0
the	0
fourth	0
vaccination	0
in	0
some	0
restricted	0
areas	0
.	0

Involvement	0
of	0
the	0
mu	0
-	0
opiate	0
receptor	0
in	0
peripheral	0
analgesia	3
.	0

The	0
intradermal	0
injection	0
of	0
mu	0
(	0
morphine	1
,	0
Tyr	1
-	2
D	2
-	2
Ala	2
-	2
Gly	2
-	2
NMe	2
-	2
Phe	2
-	2
Gly	2
-	2
ol	2
and	0
morphiceptin	1
)	0
,	0
kappa	0
(	0
trans	1
-	2
3	2
,	2
4	2
-	2
dichloro	2
-	2
N	2
-	2
methyl	2
-	2
N	2
[	2
2	2
-	2
(	2
1	2
-	2
pyrrolidinyl	2
)	2
cyclohexyl	2
]	2
benzeneactemide	2
)	0
and	0
delta	0
(	0
[	1
D	2
-	2
Pen2	2
.	2
5	2
]	2
-	2
enkephalin	2
and	0
[	1
D	2
-	2
Ser2	2
]	2
-	2
[	2
Leu	2
]	2
enkephalin	2
-	2
Thr	2
)	0
selective	0
opioid	0
-	0
agonists	0
,	0
by	0
themselves	0
,	0
did	0
not	0
significantly	0
affect	0
the	0
mechanical	0
nociceptive	0
threshold	0
in	0
the	0
hindpaw	0
of	0
the	0
rat	0
.	0

Intradermal	0
injection	0
of	0
mu	0
,	0
but	0
not	0
delta	0
or	0
kappa	0
opioid	0
-	0
agonists	0
,	0
however	0
,	0
produced	0
dose	0
-	0
dependent	0
inhibition	0
of	0
prostaglandin	1
E2	2
-	0
induced	0
hyperalgesia	3
.	0

The	0
analgesic	0
effect	0
of	0
the	0
mu	0
-	0
agonist	0
morphine	1
was	0
dose	0
-	0
dependently	0
antagonized	0
by	0
naloxone	1
and	0
prevented	0
by	0
co	0
-	0
injection	0
of	0
pertussis	0
toxin	0
.	0

Morphine	1
did	0
not	0
,	0
however	0
,	0
alter	0
the	0
hyperalgesia	3
induced	0
by	0
8	1
-	2
bromo	2
cyclic	2
adenosine	2
monophosphate	2
.	0

We	0
conclude	0
that	0
the	0
analgesic	0
action	0
of	0
opioids	0
on	0
the	0
peripheral	0
terminals	0
of	0
primary	0
afferents	0
is	0
via	0
a	0
binding	0
site	0
with	0
characteristics	0
of	0
the	0
mu	0
-	0
opioid	0
receptor	0
and	0
that	0
this	0
action	0
is	0
mediated	0
by	0
inhibition	0
of	0
the	0
cyclic	1
adenosine	2
monophosphate	2
second	0
messenger	0
system	0
.	0

Involvement	0
of	0
locus	0
coeruleus	0
and	0
noradrenergic	0
neurotransmission	0
in	0
fentanyl	1
-	0
induced	0
muscular	3
rigidity	4
in	0
the	0
rat	0
.	0

Whereas	0
muscular	3
rigidity	4
is	0
a	0
well	0
-	0
known	0
side	0
effect	0
that	0
is	0
associated	0
with	0
high	0
-	0
dose	0
fentanyl	1
anesthesia	0
,	0
a	0
paucity	0
of	0
information	0
exists	0
with	0
regard	0
to	0
its	0
underlying	0
mechanism	0
(	0
s	0
)	0
.	0

We	0
investigated	0
in	0
this	0
study	0
the	0
possible	0
engagement	0
of	0
locus	0
coeruleus	0
of	0
the	0
pons	0
in	0
this	0
phenomenon	0
,	0
using	0
male	0
Sprague	0
-	0
Dawley	0
rats	0
anesthetized	0
with	0
ketamine	1
.	0

Under	0
proper	0
control	0
of	0
respiration	0
,	0
body	0
temperature	0
and	0
end	0
-	0
tidal	0
C02	1
,	0
intravenous	0
administration	0
of	0
fentanyl	1
(	0
50	0
or	0
100	0
micrograms	0
/	0
kg	0
)	0
consistently	0
promoted	0
an	0
increase	0
in	0
electromyographic	0
activity	0
recorded	0
from	0
the	0
gastrocnemius	0
and	0
abdominal	0
rectus	0
muscles	0
.	0

Such	0
an	0
induced	0
muscular	3
rigidity	4
by	0
the	0
narcotic	0
agent	0
was	0
significantly	0
antagonized	0
or	0
even	0
reduced	0
by	0
prior	0
electrolytic	0
lesions	0
of	0
the	0
locus	0
coeruleus	0
or	0
pretreatment	0
with	0
the	0
alpha	0
-	0
adrenoceptor	0
blocker	0
,	0
prazosin	1
.	0

Microinjection	0
of	0
fentanyl	1
(	0
2	0
.	0
5	0
micrograms	0
/	0
50	0
nl	0
)	0
directly	0
into	0
this	0
pontine	0
nucleus	0
,	0
on	0
the	0
other	0
hand	0
,	0
elicited	0
discernible	0
electromyographic	0
excitation	0
.	0

It	0
is	0
speculated	0
that	0
the	0
induction	0
of	0
muscular	3
rigidity	4
by	0
fentanyl	1
may	0
involve	0
the	0
coerulospinal	0
noradrenergic	0
fibers	0
to	0
the	0
spinal	0
motoneurons	0
.	0

Dexmedetomidine	1
,	0
acting	0
through	0
central	0
alpha	0
-	0
2	0
adrenoceptors	0
,	0
prevents	0
opiate	0
-	0
induced	0
muscle	3
rigidity	4
in	0
the	0
rat	0
.	0

The	0
highly	0
-	0
selective	0
alpha	0
-	0
2	0
adrenergic	0
agonist	0
dexmedetomidine	1
(	0
D	1
-	2
MED	2
)	0
is	0
capable	0
of	0
inducing	0
muscle	3
flaccidity	4
and	0
anesthesia	0
in	0
rats	0
and	0
dogs	0
.	0

Intense	0
generalized	0
muscle	3
rigidity	4
is	0
an	0
undesirable	0
side	0
effect	0
of	0
potent	0
opiate	0
agonists	0
.	0

Although	0
the	0
neurochemistry	0
of	0
opiate	0
-	0
induced	0
rigidity	3
has	0
yet	0
to	0
be	0
fully	0
elucidated	0
,	0
recent	0
work	0
suggests	0
a	0
role	0
for	0
a	0
central	0
adrenergic	0
mechanism	0
.	0

In	0
the	0
present	0
study	0
,	0
the	0
authors	0
determined	0
if	0
treatment	0
with	0
D	1
-	2
MED	2
prevents	0
the	0
muscle	3
rigidity	4
caused	0
by	0
high	0
-	0
dose	0
alfentanil	1
anesthesia	0
in	0
the	0
rat	0
.	0

Animals	0
(	0
n	0
=	0
42	0
)	0
were	0
treated	0
intraperitoneally	0
with	0
one	0
of	0
the	0
following	0
six	0
regimens	0
:	0
1	0
)	0
L	0
-	0
MED	0
(	0
the	0
inactive	0
L	0
-	0
isomer	0
of	0
medetomidine	1
)	0
,	0
30	0
micrograms	0
/	0
kg	0
;	0
2	0
)	0
D	1
-	2
MED	2
,	0
10	0
micrograms	0
/	0
kg	0
;	0
3	0
)	0
D	1
-	2
MED	2
,	0
30	0
micrograms	0
/	0
kg	0
;	0
4	0
)	0
D	1
-	2
MED	2
[	0
30	0
micrograms	0
/	0
kg	0
]	0
and	0
the	0
central	0
-	0
acting	0
alpha	0
-	0
2	0
antagonist	0
,	0
idazoxan	1
[	0
10	0
mg	0
/	0
kg	0
]	0
;	0
5	0
)	0
D	1
-	2
MED	2
[	0
30	0
micrograms	0
/	0
kg	0
]	0
and	0
the	0
peripheral	0
-	0
acting	0
alpha	0
-	0
2	0
antagonist	0
DG	1
-	2
5128	2
[	0
10	0
mg	0
/	0
kg	0
]	0
,	0
or	0
;	0
6	0
)	0
saline	0
.	0

Baseline	0
electromyographic	0
activity	0
was	0
recorded	0
from	0
the	0
gastrocnemius	0
muscle	0
before	0
and	0
after	0
drug	0
treatment	0
.	0

Each	0
rat	0
was	0
then	0
injected	0
with	0
alfentanil	1
(	0
ALF	1
,	0
0	0
.	0
5	0
mg	0
/	0
kg	0
sc	0
)	0
.	0

ALF	1
injection	0
resulted	0
in	0
a	0
marked	0
increase	0
in	0
hindlimb	0
EMG	0
activity	0
in	0
the	0
L	0
-	0
MED	0
treatment	0
group	0
which	0
was	0
indistinguishable	0
from	0
that	0
seen	0
in	0
animals	0
treated	0
with	0
saline	0
.	0

In	0
contrast	0
,	0
D	1
-	2
MED	2
prevented	0
alfentanil	1
-	0
induced	0
muscle	3
rigidity	4
in	0
a	0
dose	0
-	0
dependent	0
fashion	0
.	0

The	0
small	0
EMG	0
values	0
obtained	0
in	0
the	0
high	0
-	0
dose	0
D	1
-	2
MED	2
group	0
were	0
comparable	0
with	0
those	0
recorded	0
in	0
earlier	0
studies	0
from	0
control	0
animals	0
not	0
given	0
any	0
opiate	0
.	0

The	0
high	0
-	0
dose	0
D	1
-	2
MED	2
animals	0
were	0
flaccid	0
,	0
akinetic	3
,	0
and	0
lacked	0
a	0
startle	3
response	0
during	0
the	0
entire	0
experimental	0
period	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Some	0
central	0
effects	0
of	0
repeated	0
treatment	0
with	0
fluvoxamine	1
.	0

We	0
investigated	0
the	0
effect	0
of	0
repeated	0
treatment	0
with	0
fluvoxamine	1
,	0
a	0
selective	0
serotonin	1
uptake	0
inhibitor	0
,	0
on	0
behavioral	0
effects	0
of	0
dopaminomimetics	0
and	0
methoxamine	1
and	0
on	0
the	0
animal	0
behavior	0
in	0
the	0
"	0
behavioral	0
despair	0
"	0
test	0
.	0

A	0
repeated	0
treatment	0
with	0
fluvoxamine	1
(	0
twice	0
daily	0
for	0
14	0
days	0
)	0
potentiated	0
in	0
mice	0
and	0
in	0
rats	0
(	0
weaker	0
)	0
the	0
amphetamine	1
-	0
induced	0
hyperactivity	3
.	0

The	0
hyperactivity	3
induced	0
by	0
nomifensine	1
in	0
mice	0
remained	0
unaffected	0
by	0
fluvoxamine	1
.	0

The	0
stimulation	0
of	0
locomotor	0
activity	0
by	0
intracerebroventricularly	0
administered	0
methoxamine	1
was	0
not	0
affected	0
by	0
repeated	0
treatment	0
with	0
fluvoxamine	1
.	0

Given	0
three	0
times	0
fluvoxamine	1
had	0
no	0
effect	0
on	0
the	0
immobilization	0
time	0
in	0
the	0
"	0
behavioral	0
despair	0
"	0
test	0
in	0
rats	0
.	0

The	0
results	0
indicate	0
that	0
fluvoxamine	1
given	0
repeatedly	0
acts	0
differently	0
than	0
citalopram	1
,	0
another	0
selective	0
serotonin	1
uptake	0
inhibitor	0
,	0
and	0
differs	0
also	0
from	0
other	0
antidepressant	0
drugs	0
.	0

Protective	0
effect	0
of	0
a	0
specific	0
platelet	0
-	0
activating	0
factor	0
antagonist	0
,	0
BN	1
52021	2
,	0
on	0
bupivacaine	1
-	0
induced	0
cardiovascular	3
impairments	4
in	0
rats	0
.	0

Administration	0
of	0
the	0
local	0
anaesthetic	0
bupivacaine	1
(	0
1	0
.	0
5	0
or	0
2	0
mg	0
/	0
kg	0
,	0
i	0
.	0
v	0
.	0
)	0
to	0
rats	0
elicited	0
a	0
marked	0
decrease	3
of	4
mean	4
arterial	4
blood	4
pressure	4
(	4
MBP	4
)	4
and	4
heart	4
rate	4
(	4
HR	4
)	4
leading	0
to	0
death	0
(	0
in	0
67	0
%	0
or	0
90	0
%	0
of	0
animals	0
respectively	0
)	0
.	0

Intravenous	0
injection	0
of	0
the	0
specific	0
platelet	0
-	0
activating	0
factor	0
(	0
PAF	0
)	0
antagonist	0
BN	1
52021	2
(	0
10	0
mg	0
/	0
kg	0
)	0
,	0
30	0
min	0
before	0
bupivacaine	1
administration	0
(	0
2	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
suppressed	0
both	0
the	0
decrease	3
of	4
MBP	4
and	4
HR	4
.	0

In	0
contrast	0
,	0
doses	0
of	0
1	0
mg	0
/	0
kg	0
BN	1
52021	2
given	0
30	0
min	0
before	0
or	0
10	0
mg	0
/	0
kg	0
administered	0
5	0
min	0
before	0
i	0
.	0
v	0
.	0
injection	0
of	0
bupivacaine	1
were	0
ineffective	0
.	0

When	0
BN	1
52021	2
(	0
20	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
was	0
injected	0
immediately	0
after	0
bupivacaine	1
(	0
2	0
mg	0
/	0
kg	0
)	0
,	0
a	0
partial	0
reversion	0
of	0
the	0
decrease	3
of	4
MBP	4
and	4
HR	4
was	0
observed	0
,	0
whereas	0
the	0
dose	0
of	0
10	0
mg	0
/	0
kg	0
was	0
ineffective	0
.	0

A	0
partial	0
recovery	0
of	0
bupivacaine	1
-	0
induced	0
ECG	0
alterations	0
was	0
observed	0
after	0
pretreatment	0
of	0
the	0
rats	0
with	0
BN	1
52021	2
.	0

Since	0
the	0
administration	0
of	0
BN	1
52021	2
,	0
at	0
all	0
doses	0
studied	0
,	0
did	0
not	0
alter	0
MBP	0
and	0
HR	0
at	0
the	0
doses	0
used	0
,	0
the	0
bulk	0
of	0
these	0
results	0
clearly	0
demonstrate	0
a	0
protective	0
action	0
of	0
BN	1
52021	2
,	0
a	0
specific	0
antagonist	0
of	0
PAF	0
,	0
against	0
bupivacaine	1
-	0
induced	0
cardiovascular	3
toxicity	4
.	0

Thus	0
,	0
consistent	0
with	0
its	0
direct	0
effect	0
on	0
heart	0
,	0
PAF	0
appears	0
to	0
be	0
implicated	0
in	0
bupivacaine	1
-	0
induced	0
cardiovascular	3
alterations	4
.	0

The	0
epidemiology	0
of	0
the	0
acute	0
flank	3
pain	4
syndrome	0
from	0
suprofen	1
.	0

Suprofen	1
,	0
a	0
new	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
drug	0
,	0
was	0
marketed	0
in	0
early	0
1986	0
as	0
an	0
analgesic	0
agent	0
.	0

Until	0
physicians	0
began	0
reporting	0
an	0
unusual	0
acute	0
flank	3
pain	4
syndrome	0
to	0
the	0
spontaneous	0
reporting	0
system	0
,	0
700	0
,	0
000	0
persons	0
used	0
the	0
drug	0
in	0
the	0
United	0
States	0
.	0

Through	0
August	0
1986	0
,	0
a	0
total	0
of	0
163	0
cases	0
of	0
this	0
syndrome	0
were	0
reported	0
.	0

To	0
elucidate	0
the	0
epidemiology	0
of	0
the	0
syndrome	0
,	0
a	0
case	0
-	0
control	0
study	0
was	0
performed	0
,	0
comparing	0
62	0
of	0
the	0
case	0
patients	0
who	0
had	0
been	0
reported	0
to	0
the	0
spontaneous	0
reporting	0
system	0
to	0
185	0
suprofen	1
-	0
exposed	0
control	0
subjects	0
who	0
did	0
not	0
have	0
the	0
syndrome	0
.	0

Case	0
patients	0
were	0
more	0
likely	0
to	0
be	0
men	0
(	0
odds	0
ratio	0
,	0
3	0
.	0
8	0
;	0
95	0
%	0
confidence	0
interval	0
,	0
1	0
.	0
2	0
-	0
12	0
.	0
1	0
)	0
,	0
suffer	0
from	0
hay	3
fever	4
and	0
asthma	3
(	0
odds	0
ratio	0
,	0
3	0
.	0
4	0
;	0
95	0
%	0
confidence	0
interval	0
,	0
1	0
.	0
0	0
-	0
11	0
.	0
9	0
)	0
;	0
to	0
participate	0
in	0
regular	0
exercise	0
(	0
odds	0
ratio	0
,	0
5	0
.	0
9	0
;	0
95	0
%	0
confidence	0
interval	0
,	0
1	0
.	0
1	0
-	0
30	0
.	0
7	0
)	0
,	0
especially	0
in	0
the	0
use	0
of	0
Nautilus	0
equipment	0
(	0
p	0
=	0
0	0
.	0
02	0
)	0
;	0
and	0
to	0
use	0
alcohol	1
(	0
odds	0
ratio	0
,	0
4	0
.	0
4	0
;	0
95	0
%	0
confidence	0
interval	0
,	0
1	0
.	0
1	0
-	0
17	0
.	0
5	0
)	0
.	0

Possible	0
risk	0
factors	0
included	0
young	0
age	0
,	0
concurrent	0
use	0
of	0
other	0
analgesic	0
agents	0
(	0
especially	0
ibuprofen	1
)	0
,	0
preexisting	0
renal	3
disease	4
,	0
a	0
history	0
of	0
kidney	3
stones	4
,	0
a	0
history	0
of	0
gout	3
,	0
a	0
recent	0
increase	0
in	0
activity	0
,	0
a	0
recent	0
increase	0
in	0
sun	0
exposure	0
,	0
and	0
residence	0
in	0
the	0
Sunbelt	0
.	0

These	0
were	0
findings	0
that	0
were	0
suggestive	0
but	0
did	0
not	0
reach	0
conventional	0
statistical	0
significance	0
.	0

These	0
findings	0
are	0
consistent	0
with	0
the	0
postulated	0
mechanism	0
for	0
this	0
unusual	0
syndrome	0
:	0
acute	0
diffuse	0
crystallization	0
of	0
uric	1
acid	2
in	0
renal	0
tubules	0
.	0

Phlorizin	1
-	0
induced	0
glycosuria	3
does	0
not	0
prevent	0
gentamicin	1
nephrotoxicity	3
in	0
rats	0
.	0

Because	0
rats	0
with	0
streptozotocin	1
-	0
induced	0
diabetes	3
mellitus	4
(	0
DM	3
)	0
have	0
a	0
high	0
solute	0
diuresis	0
(	0
glycosuria	3
of	0
10	0
to	0
12	0
g	0
/	0
day	0
)	0
,	0
we	0
have	0
suggested	0
that	0
this	0
may	0
in	0
part	0
be	0
responsible	0
for	0
their	0
resistance	0
to	0
gentamicin	1
-	0
induced	0
acute	3
renal	4
failure	4
(	0
ARF	3
)	0
.	0

The	0
protection	0
from	0
gentamicin	1
nephrotoxicity	3
was	0
studied	0
in	0
non	0
-	0
diabetic	3
rats	0
with	0
chronic	0
solute	0
diuresis	0
induced	0
by	0
blockage	0
of	0
tubular	0
glucose	1
reabsorption	0
with	0
phlorizin	1
(	0
P	1
)	0
.	0

DM	3
rats	0
with	0
mild	0
glycosuria	3
(	0
similar	0
in	0
degree	0
to	0
that	0
of	0
the	0
P	1
treated	0
animals	0
)	0
were	0
also	0
studied	0
.	0

Unanesthetized	0
adult	0
female	0
,	0
Sprague	0
-	0
Dawley	0
rats	0
were	0
divided	0
in	0
four	0
groups	0
and	0
studied	0
for	0
15	0
days	0
.	0

Group	0
1	0
(	0
P	1
alone	0
)	0
received	0
P	1
,	0
360	0
mg	0
/	0
day	0
,	0
for	0
15	0
days	0
;	0
Group	0
II	0
(	0
P	1
+	0
gentamicin	1
)	0
;	0
Group	0
III	0
(	0
gentamicin	1
alone	0
)	0
and	0
Group	0
IV	0
(	0
mild	0
DM	3
+	0
gentamicin	1
)	0
.	0

Nephrotoxic	3
doses	0
(	0
40	0
mg	0
/	0
kg	0
body	0
wt	0
/	0
day	0
)	0
of	0
gentamicin	1
were	0
injected	0
during	0
the	0
last	0
nine	0
days	0
of	0
study	0
to	0
the	0
animals	0
of	0
groups	0
II	0
to	0
IV	0
.	0

In	0
Group	0
I	0
,	0
P	1
induced	0
a	0
moderate	0
and	0
stable	0
glycosuria	3
(	0
3	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
1	0
g	0
/	0
day	0
,	0
SE	0
)	0
,	0
and	0
no	0
functional	0
or	0
morphologic	0
evidence	0
of	0
renal	3
dysfunction	4
(	0
baseline	0
CCr	0
2	0
.	0
1	0
+	0
/	0
-	0
0	0
.	0
1	0
ml	0
/	0
min	0
,	0
undetectable	0
lysozymuria	0
)	0
or	0
damage	0
(	0
tubular	3
necrosis	4
score	0
[	0
maximum	0
4	0
]	0
,	0
zero	0
)	0
.	0

In	0
Group	0
II	0
,	0
P	1
did	0
not	0
prevent	0
gentamicin	1
-	0
ARF	3
(	0
maximal	0
decrease	0
in	0
CCr	0
at	0
day	0
9	0
.	0
89	0
%	0
,	0
P	1
less	0
than	0
0	0
.	0
001	0
;	0
peak	0
lysozymuria	0
,	0
1863	0
+	0
/	0
-	0
321	0
micrograms	0
/	0
day	0
;	0
and	0
tubular	3
necrosis	4
score	0
,	0
3	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
1	0
)	0
.	0

These	0
values	0
were	0
not	0
different	0
from	0
those	0
of	0
Group	0
III	0
:	0
maximal	0
decrease	0
in	0
CCr	0
73	0
%	0
(	0
P	1
less	0
than	0
0	0
.	0
001	0
)	0
;	0
lysozymuria	0
,	0
2147	0
+	0
/	0
-	0
701	0
micrograms	0
/	0
day	0
;	0
tubular	3
necrosis	4
score	0
,	0
3	0
.	0
8	0
+	0
/	0
-	0
0	0
.	0
1	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Catalepsy	3
induced	0
by	0
combinations	0
of	0
ketamine	1
and	0
morphine	1
:	0
potentiation	0
,	0
antagonism	0
,	0
tolerance	0
and	0
cross	0
-	0
tolerance	0
in	0
the	0
rat	0
.	0

Previous	0
studies	0
demonstrated	0
that	0
both	0
ketamine	1
and	0
morphine	1
induced	0
analgesia	3
and	0
catalepsy	3
in	0
the	0
rat	0
.	0

Pre	0
-	0
treatment	0
with	0
ketamine	1
produced	0
cross	0
-	0
tolerance	0
to	0
morphine	1
,	0
whereas	0
pretreatment	0
with	0
morphine	1
did	0
not	0
induce	0
cross	0
-	0
tolerance	0
to	0
ketamine	1
but	0
rather	0
augmented	0
the	0
cataleptic	3
response	0
;	0
this	0
augmentation	0
was	0
attributed	0
to	0
residual	0
morphine	1
in	0
the	0
brain	0
.	0

The	0
present	0
studies	0
explored	0
the	0
duration	0
of	0
the	0
loss	0
of	0
righting	0
reflex	0
induced	0
by	0
sub	0
-	0
effective	0
doses	0
of	0
ketamine	1
and	0
morphine	1
,	0
administered	0
simultaneously	0
.	0

There	0
was	0
mutual	0
potentiation	0
between	0
sub	0
-	0
effective	0
doses	0
of	0
ketamine	1
and	0
morphine	1
,	0
but	0
sub	0
-	0
effective	0
doses	0
of	0
ketamine	1
partly	0
antagonized	0
fully	0
-	0
effective	0
doses	0
of	0
morphine	1
.	0

Latency	0
to	0
the	0
loss	0
of	0
righting	0
reflex	0
,	0
rigidity	3
and	0
behavior	0
on	0
recovery	0
,	0
reflected	0
the	0
relative	0
predominance	0
of	0
ketamine	1
or	0
morphine	1
in	0
each	0
combination	0
.	0

Naloxone	1
inhibited	0
the	0
induced	0
cataleptic	3
effects	0
.	0

The	0
degree	0
and	0
time	0
course	0
of	0
development	0
of	0
tolerance	0
to	0
daily	0
administration	0
of	0
sub	0
-	0
effective	0
dose	0
combinations	0
of	0
ketamine	1
and	0
morphine	1
were	0
similar	0
.	0

Rats	0
,	0
tolerant	0
to	0
ketamine	1
-	0
dominant	0
combinations	0
,	0
were	0
cross	0
-	0
tolerant	0
to	0
both	0
drugs	0
,	0
while	0
those	0
tolerant	0
to	0
morphine	1
-	0
dominant	0
combinations	0
were	0
cross	0
-	0
tolerant	0
to	0
morphine	1
but	0
showed	0
either	0
no	0
cross	0
-	0
tolerance	0
or	0
an	0
augmented	0
response	0
to	0
ketamine	1
.	0

While	0
the	0
mutual	0
potentiation	0
,	0
antagonism	0
and	0
tolerance	0
suggest	0
common	0
mechanisms	0
for	0
the	0
induced	0
catalepsy	3
,	0
differences	0
in	0
latency	0
,	0
rigidity	3
and	0
behavior	0
,	0
asymmetry	0
of	0
cross	0
-	0
tolerance	0
and	0
a	0
widely	0
-	0
different	0
ID50	0
for	0
naloxone	1
would	0
argue	0
against	0
an	0
action	0
at	0
a	0
single	0
opioid	0
site	0
.	0

Hydrocortisone	1
-	0
induced	0
hypertension	3
in	0
humans	0
:	0
pressor	0
responsiveness	0
and	0
sympathetic	0
function	0
.	0

0ral	0
hydrocortisone	1
increases	0
blood	0
pressure	0
and	0
enhances	0
pressor	0
responsiveness	0
in	0
normal	0
human	0
subjects	0
.	0

We	0
studied	0
the	0
effects	0
of	0
1	0
week	0
of	0
oral	0
hydrocortisone	1
(	0
200	0
mg	0
/	0
day	0
)	0
on	0
blood	0
pressure	0
,	0
cardiac	0
output	0
,	0
total	0
peripheral	0
resistance	0
,	0
forearm	0
vascular	0
resistance	0
,	0
and	0
norepinephrine	1
spillover	0
to	0
plasma	0
in	0
eight	0
healthy	0
male	0
volunteers	0
.	0

Although	0
diastolic	0
blood	0
pressure	0
remained	0
unchanged	0
,	0
systolic	0
blood	0
pressure	0
increased	0
from	0
119	0
to	0
135	0
mm	0
Hg	0
(	0
SED	0
+	0
/	0
-	0
3	0
.	0
4	0
,	0
p	0
less	0
than	0
0	0
.	0
01	0
)	0
,	0
associated	0
with	0
an	0
increased	3
cardiac	4
output	4
(	0
5	0
.	0
85	0
-	0
7	0
.	0
73	0
l	0
/	0
min	0
,	0
SED	0
+	0
/	0
-	0
0	0
.	0
46	0
,	0
p	0
less	0
than	0
0	0
.	0
01	0
)	0
.	0

Total	0
peripheral	0
vascular	0
resistance	0
fell	0
from	0
15	0
.	0
1	0
to	0
12	0
.	0
2	0
mm	0
Hg	0
/	0
l	0
/	0
min	0
(	0
SED	0
+	0
/	0
-	0
1	0
.	0
03	0
,	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

Resting	0
forearm	0
vascular	0
resistance	0
remained	0
unchanged	0
,	0
but	0
the	0
reflex	0
response	0
to	0
the	0
cold	0
pressor	0
test	0
was	0
accentuated	0
,	0
the	0
rise	0
in	0
resistance	0
increasing	0
from	0
10	0
.	0
5	0
mm	0
Hg	0
/	0
ml	0
/	0
100	0
ml	0
/	0
min	0
(	0
R	0
units	0
)	0
before	0
treatment	0
to	0
32	0
.	0
6	0
R	0
units	0
after	0
treatment	0
(	0
SED	0
+	0
/	0
-	0
6	0
.	0
4	0
,	0
p	0
less	0
than	0
0	0
.	0
025	0
)	0
.	0

The	0
rise	0
in	0
forearm	0
vascular	0
resistance	0
accompanying	0
intra	0
-	0
arterial	0
norepinephrine	1
(	0
25	0
,	0
50	0
,	0
and	0
100	0
ng	0
/	0
min	0
)	0
was	0
also	0
significantly	0
greater	0
after	0
hydrocortisone	1
,	0
increasing	0
from	0
an	0
average	0
of	0
14	0
.	0
9	0
+	0
/	0
-	0
2	0
.	0
4	0
R	0
units	0
before	0
treatment	0
to	0
35	0
.	0
1	0
+	0
/	0
-	0
5	0
.	0
5	0
R	0
units	0
after	0
hydrocortisone	1
(	0
SED	0
+	0
/	0
-	0
6	0
.	0
0	0
,	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

A	0
shift	0
to	0
the	0
left	0
in	0
the	0
dose	0
-	0
response	0
relation	0
and	0
fall	0
in	0
threshold	0
suggested	0
increased	0
sensitivity	0
to	0
norepinephrine	1
after	0
treatment	0
.	0

Measurement	0
of	0
resting	0
norepinephrine	1
spillover	0
rate	0
to	0
plasma	0
and	0
norepinephrine	1
uptake	0
indicated	0
that	0
overall	0
resting	0
sympathetic	0
nervous	0
system	0
activity	0
was	0
not	0
increased	0
.	0

The	0
rise	3
in	4
resting	4
blood	4
pressure	4
with	0
hydrocortisone	1
is	0
associated	0
with	0
an	0
increased	3
cardiac	4
output	4
(	0
presumably	0
due	0
to	0
increased	0
blood	0
volume	0
)	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Neuromuscular	3
blockade	4
with	0
magnesium	1
sulfate	2
and	0
nifedipine	1
.	0

A	0
patient	0
who	0
received	0
tocolysis	0
with	0
nifedipine	1
developed	0
neuromuscular	3
blockade	4
after	0
500	0
mg	0
of	0
magnesium	1
sulfate	2
was	0
administered	0
.	0

This	0
reaction	0
demonstrates	0
that	0
nifedipine	1
can	0
seriously	0
potentiate	0
the	0
toxicity	3
of	0
magnesium	1
.	0

Caution	0
should	0
be	0
exercised	0
when	0
these	0
two	0
tocolytics	0
are	0
combined	0
.	0

Chronic	0
carbamazepine	1
inhibits	0
the	0
development	0
of	0
local	0
anesthetic	0
seizures	3
kindled	0
by	0
cocaine	1
and	0
lidocaine	1
.	0

The	0
effects	0
of	0
carbamazepine	1
(	0
CBZ	1
)	0
treatment	0
on	0
local	0
anesthetic	0
-	0
kindled	0
seizures	3
and	0
lethality	0
were	0
evaluated	0
in	0
different	0
stages	0
of	0
the	0
kindling	0
process	0
and	0
under	0
different	0
methods	0
of	0
CBZ	1
administration	0
.	0

Chronic	0
oral	0
CBZ	1
inhibited	0
the	0
development	0
of	0
both	0
lidocaine	1
-	0
and	0
cocaine	1
-	0
induced	0
seizures	3
,	0
but	0
had	0
little	0
effect	0
on	0
the	0
fully	0
developed	0
local	0
anesthetic	0
seizures	3
.	0

Chronic	0
CBZ	1
also	0
decreased	0
the	0
incidence	0
of	0
seizure	3
-	0
related	0
mortality	0
in	0
the	0
cocaine	1
-	0
injected	0
rats	0
.	0

Acute	0
CBZ	1
over	0
a	0
range	0
of	0
doses	0
(	0
15	0
-	0
50	0
mg	0
/	0
kg	0
)	0
had	0
no	0
effect	0
on	0
completed	0
lidocaine	1
-	0
kindled	0
or	0
acute	0
cocaine	1
-	0
induced	0
seizures	3
.	0

Repeated	0
i	0
.	0
p	0
.	0
injection	0
of	0
CBZ	1
(	0
15	0
mg	0
/	0
kg	0
)	0
also	0
was	0
without	0
effect	0
on	0
the	0
development	0
of	0
lidocaine	1
-	0
or	0
cocaine	1
-	0
kindled	0
seizures	3
.	0

The	0
differential	0
effects	0
of	0
CBZ	1
depending	0
upon	0
stage	0
of	0
seizure	3
development	0
suggest	0
that	0
distinct	0
mechanisms	0
underlie	0
the	0
development	0
versus	0
maintenance	0
of	0
local	0
anesthetic	0
-	0
kindled	0
seizures	3
.	0

The	0
effectiveness	0
of	0
chronic	0
but	0
not	0
repeated	0
,	0
intermittent	0
injections	0
of	0
CBZ	1
suggests	0
that	0
different	0
biochemical	0
consequences	0
result	0
from	0
the	0
different	0
treatment	0
regimens	0
.	0

The	0
possible	0
utility	0
of	0
chronic	0
CBZ	1
in	0
preventing	0
the	0
development	0
of	0
toxic	0
side	0
effects	0
in	0
human	0
cocaine	1
users	0
is	0
suggested	0
by	0
these	0
data	0
,	0
but	0
remains	0
to	0
be	0
directly	0
evaluated	0
.	0

Magnetic	0
resonance	0
imaging	0
of	0
cerebral	0
venous	3
thrombosis	4
secondary	0
to	0
"	0
low	0
-	0
dose	0
"	0
birth	0
control	0
pills	0
.	0

The	0
clinical	0
and	0
radiographic	0
features	0
of	0
cerebral	0
deep	3
venous	4
thrombosis	4
in	0
a	0
21	0
-	0
year	0
-	0
old	0
white	0
woman	0
are	0
presented	0
.	0

This	0
nulliparous	0
patient	0
presented	0
with	0
relatively	0
mild	0
clinical	0
symptoms	0
and	0
progressing	0
mental	0
status	0
changes	0
.	0

The	0
only	0
known	0
risk	0
factor	0
was	0
"	0
low	0
-	0
dose	0
"	0
oral	1
contraceptive	2
pills	0
.	0

The	0
magnetic	0
resonance	0
image	0
(	0
MRI	0
)	0
showed	0
increased	0
signal	0
intensity	0
from	0
the	0
internal	0
cerebral	0
veins	0
,	0
vein	0
of	0
Galen	0
,	0
and	0
straight	0
sinus	0
.	0

The	0
diagnosis	0
was	0
confirmed	0
by	0
arterial	0
angiography	0
.	0

Beta	0
-	0
2	0
-	0
adrenoceptor	0
-	0
mediated	0
hypokalemia	3
and	0
its	0
abolishment	0
by	0
oxprenolol	1
.	0

The	0
time	0
course	0
and	0
concentration	0
-	0
effect	0
relationship	0
of	0
terbutaline	1
-	0
induced	0
hypokalemia	3
was	0
studied	0
,	0
using	0
computer	0
-	0
aided	0
pharmacokinetic	0
-	0
dynamic	0
modeling	0
.	0

Subsequently	0
we	0
investigated	0
the	0
efficacy	0
of	0
oxprenolol	1
in	0
antagonizing	0
such	0
hypokalemia	3
,	0
together	0
with	0
the	0
pharmacokinetic	0
interaction	0
between	0
both	0
drugs	0
.	0

Six	0
healthy	0
subjects	0
were	0
given	0
a	0
0	0
.	0
5	0
mg	0
subcutaneous	0
dose	0
of	0
terbutaline	1
on	0
two	0
occasions	0
:	0
1	0
hour	0
after	0
oral	0
administration	0
of	0
a	0
placebo	0
and	0
1	0
hour	0
after	0
80	0
mg	0
oxprenolol	1
orally	0
.	0

In	0
the	0
7	0
-	0
hour	0
period	0
after	0
terbutaline	1
administration	0
,	0
plasma	0
samples	0
were	0
taken	0
for	0
determination	0
of	0
plasma	0
potassium	1
levels	0
and	0
drug	0
concentrations	0
.	0

The	0
sigmoid	0
Emax	0
model	0
offered	0
a	0
good	0
description	0
of	0
the	0
relation	0
between	0
terbutaline	1
concentrations	0
and	0
potassium	1
effects	0
.	0

0xprenolol	1
caused	0
decreases	0
of	0
65	0
%	0
and	0
56	0
%	0
of	0
terbutaline	1
volume	0
of	0
distribution	0
and	0
clearance	0
,	0
respectively	0
,	0
and	0
an	0
increase	0
of	0
130	0
%	0
of	0
its	0
AUC	0
.	0

In	0
spite	0
of	0
higher	0
terbutaline	1
concentrations	0
after	0
oxprenolol	1
pretreatment	0
,	0
the	0
hypokalemia	3
was	0
almost	0
completely	0
antagonized	0
by	0
the	0
beta	0
2	0
-	0
blocking	0
action	0
.	0

A	0
dystonia	3
-	0
like	0
syndrome	0
after	0
neuropeptide	0
(	0
MSH	1
/	0
ACTH	1
)	0
stimulation	0
of	0
the	0
rat	0
locus	0
ceruleus	0
.	0

The	0
movement	3
disorder	4
investigated	0
in	0
these	0
studies	0
has	0
some	0
features	0
in	0
common	0
with	0
human	0
idiopathic	0
dystonia	3
,	0
and	0
information	0
obtained	0
in	0
these	0
studies	0
may	0
be	0
of	0
potential	0
clinical	0
benefit	0
.	0

The	0
present	0
experimental	0
results	0
indicated	0
that	0
peptidergic	0
stimulation	0
of	0
the	0
LC	0
resulted	0
in	0
a	0
NE	0
-	0
mediated	0
inhibition	0
of	0
cerebellar	0
Purkinje	0
cells	0
located	0
at	0
terminals	0
of	0
the	0
ceruleo	0
-	0
cerebellar	0
pathway	0
.	0

However	0
,	0
it	0
is	0
not	0
certain	0
as	0
to	0
the	0
following	0
:	0
(	0
a	0
)	0
what	0
receptors	0
were	0
stimulated	0
by	0
the	0
ACTH	1
N	0
-	0
terminal	0
fragments	0
at	0
the	0
LC	0
that	0
resulted	0
in	0
this	0
disorder	0
;	0
(	0
b	0
)	0
whether	0
NE	0
,	0
released	0
onto	0
Purkinje	0
cell	0
synapses	0
located	0
at	0
terminals	0
of	0
the	0
ceruleo	0
-	0
cerebellar	0
pathway	0
,	0
did	0
indeed	0
cause	0
the	0
long	0
-	0
term	0
depression	3
at	0
Purkinje	0
cell	0
synapses	0
(	0
previously	0
described	0
by	0
others	0
)	0
that	0
resulted	0
in	0
the	0
long	0
duration	0
of	0
the	0
movement	3
disorder	4
;	0
(	0
c	0
)	0
whether	0
the	0
inhibition	0
of	0
inhibitory	0
Purkinje	0
cells	0
resulted	0
in	0
disinhibition	0
or	0
increased	0
excitability	0
of	0
the	0
unilateral	0
cerebellar	0
fastigial	0
or	0
interpositus	0
nuclei	0
,	0
the	0
output	0
targets	0
of	0
the	0
Purkinje	0
cell	0
axons	0
,	0
that	0
may	0
have	0
been	0
an	0
important	0
contributing	0
factor	0
to	0
this	0
disorder	0
.	0

These	0
questions	0
are	0
currently	0
being	0
investigated	0
.	0

Enhanced	0
stimulus	0
-	0
induced	0
neurotransmitter	0
overflow	0
in	0
epinephrine	1
-	0
induced	0
hypertensive	3
rats	0
is	0
not	0
mediated	0
by	0
prejunctional	0
beta	0
-	0
adrenoceptor	0
activation	0
.	0

The	0
present	0
study	0
examines	0
the	0
effect	0
of	0
6	0
-	0
day	0
epinephrine	1
treatment	0
(	0
100	0
micrograms	0
/	0
kg	0
per	0
h	0
,	0
s	0
.	0
c	0
.	0
)	0
on	0
stimulus	0
-	0
induced	0
(	0
1	0
Hz	0
)	0
endogenous	0
neurotransmitter	0
overflow	0
from	0
the	0
isolated	0
perfused	0
kidney	0
of	0
vehicle	0
-	0
and	0
epinephrine	1
-	0
treated	0
rats	0
.	0

Renal	0
catecholamine	1
stores	0
and	0
stimulus	0
-	0
induced	0
overflow	0
in	0
the	0
vehicle	0
-	0
treated	0
group	0
consisted	0
of	0
norepinephrine	1
only	0
.	0

However	0
,	0
epinephrine	1
treatment	0
resulted	0
in	0
the	0
incorporation	0
of	0
epinephrine	1
into	0
renal	0
catecholamine	1
stores	0
such	0
that	0
approximately	0
40	0
%	0
of	0
the	0
catecholamine	1
present	0
was	0
epinephrine	1
while	0
the	0
norepinephrine	1
content	0
was	0
reduced	0
by	0
a	0
similar	0
degree	0
.	0

Total	0
tissue	0
catecholamine	1
content	0
of	0
the	0
kidney	0
on	0
a	0
molar	0
basis	0
was	0
unchanged	0
.	0

Stimulus	0
-	0
induced	0
fractional	0
overflow	0
of	0
neurotransmitter	0
from	0
the	0
epinephrine	1
-	0
treated	0
kidneys	0
was	0
approximately	0
twice	0
normal	0
and	0
consisted	0
of	0
both	0
norepinephrine	1
and	0
epinephrine	1
in	0
proportions	0
similar	0
to	0
those	0
found	0
in	0
the	0
kidney	0
.	0

This	0
difference	0
in	0
fractional	0
overflow	0
between	0
groups	0
was	0
not	0
affected	0
by	0
neuronal	0
and	0
extraneuronal	0
uptake	0
blockade	0
.	0

Propranolol	1
had	0
no	0
effect	0
on	0
stimulus	0
-	0
induced	0
overflow	0
in	0
either	0
group	0
.	0

Phentolamine	1
increased	0
stimulus	0
-	0
induced	0
overflow	0
in	0
both	0
groups	0
although	0
the	0
increment	0
in	0
overflow	0
was	0
greater	0
in	0
the	0
epinephrine	1
-	0
treated	0
group	0
.	0

In	0
conclusion	0
,	0
chronic	0
epinephrine	1
treatment	0
results	0
in	0
enhanced	0
fractional	0
neurotransmitter	0
overflow	0
.	0

However	0
,	0
neither	0
alterations	0
in	0
prejunctional	0
beta	0
-	0
adrenoceptor	0
influences	0
nor	0
alterations	0
in	0
neuronal	0
and	0
extraneuronal	0
uptake	0
mechanisms	0
appear	0
to	0
be	0
responsible	0
for	0
this	0
alteration	0
.	0

Furthermore	0
,	0
data	0
obtained	0
with	0
phentolamine	1
alone	0
do	0
not	0
suggest	0
alpha	0
-	0
adrenoceptor	0
desensitization	0
as	0
the	0
cause	0
of	0
the	0
enhanced	0
neurotransmitter	0
overflow	0
after	0
epinephrine	1
treatment	0
.	0

GABA	1
involvement	0
in	0
naloxone	1
induced	0
reversal	0
of	0
respiratory	3
paralysis	4
produced	0
by	0
thiopental	1
.	0

No	0
agent	0
is	0
yet	0
available	0
to	0
reverse	0
respiratory	3
paralysis	4
produced	0
by	0
CNS	0
depressants	0
,	0
such	0
as	0
general	0
anesthetics	0
.	0

In	0
this	0
study	0
naloxone	1
reversed	0
respiratory	3
paralysis	4
induced	0
by	0
thiopental	1
in	0
rats	0
.	0

25	0
mg	0
/	0
kg	0
,	0
i	0
.	0
v	0
.	0
thiopental	1
produced	0
anesthesia	0
without	0
altering	0
respiratory	0
rate	0
,	0
increased	0
GABA	1
,	0
decreased	0
glutamate	1
,	0
and	0
had	0
no	0
effect	0
on	0
aspartate	1
or	0
glycine	1
levels	0
compared	0
to	0
controls	0
in	0
rat	0
cortex	0
and	0
brain	0
stem	0
.	0

Pretreatment	0
of	0
rats	0
with	0
thiosemicarbazide	1
for	0
30	0
minutes	0
abolished	0
the	0
anesthetic	0
action	0
as	0
well	0
as	0
the	0
respiratory	0
depressant	0
action	0
of	0
thiopental	1
.	0

50	0
mg	0
/	0
kg	0
,	0
i	0
.	0
v	0
.	0
thiopental	1
produced	0
respiratory	3
arrest	4
with	0
further	0
increase	0
in	0
GABA	1
and	0
decrease	0
in	0
glutamate	1
again	0
in	0
cortex	0
and	0
brain	0
stem	0
without	0
affecting	0
any	0
of	0
the	0
amino	1
acids	2
studied	0
in	0
four	0
regions	0
of	0
rat	0
brain	0
.	0

Naloxone	1
(	0
2	0
.	0
5	0
mg	0
/	0
kg	0
,	0
i	0
.	0
v	0
.	0
)	0
reversed	0
respiratory	3
paralysis	4
,	0
glutamate	1
and	0
GABA	1
levels	0
to	0
control	0
values	0
in	0
brain	0
stem	0
and	0
cortex	0
with	0
no	0
changes	0
in	0
caudate	0
or	0
cerebellum	0
.	0

These	0
data	0
suggest	0
naloxone	1
reverses	0
respiratory	3
paralysis	4
produced	0
by	0
thiopental	1
and	0
involves	0
GABA	1
in	0
its	0
action	0
.	0

Diazepam	1
facilitates	0
reflex	0
bradycardia	3
in	0
conscious	0
rats	0
.	0

The	0
effects	0
of	0
diazepam	1
on	0
cardiovascular	0
function	0
were	0
assessed	0
in	0
conscious	0
rats	0
.	0

Intravenous	0
administration	0
of	0
diazepam	1
(	0
1	0
-	0
30	0
mg	0
kg	0
-	0
1	0
)	0
produced	0
a	0
dose	0
-	0
dependent	0
decrease	0
in	0
both	0
the	0
mean	0
arterial	0
pressure	0
and	0
the	0
heart	0
rate	0
.	0

Also	0
,	0
reflex	0
bradycardia	3
was	0
produced	0
in	0
rats	0
by	0
intravenous	0
infusion	0
of	0
adrenaline	1
(	0
1	0
.	0
25	0
-	0
2	0
.	0
5	0
micrograms	0
kg	0
-	0
1	0
)	0
.	0

Intravenous	0
pretreatment	0
of	0
the	0
rats	0
with	0
diazepam	1
,	0
although	0
causing	0
no	0
change	0
in	0
the	0
adrenaline	1
-	0
induced	0
pressor	0
effect	0
,	0
did	0
enhance	0
the	0
adrenaline	1
-	0
induced	0
reflex	0
bradycardia	3
.	0

However	0
,	0
the	0
diazepam	1
enhancement	0
of	0
adrenaline	1
-	0
induced	0
reflex	0
bradycardia	3
was	0
antagonized	0
by	0
pretreatment	0
of	0
rats	0
with	0
an	0
intravenous	0
dose	0
of	0
picrotoxin	1
(	0
an	0
agent	0
blocks	0
chloride	1
channels	0
by	0
binding	0
to	0
sites	0
associated	0
with	0
the	0
benzodiazepine	1
-	0
GABA	1
-	0
chloride	1
channel	0
macromolecular	0
complex	0
)	0
.	0

The	0
data	0
indicate	0
that	0
diazepam	1
acts	0
through	0
the	0
benzodiazepine	1
-	0
GABA	1
-	0
chloride	1
channel	0
macromolecular	0
complex	0
within	0
the	0
central	0
nervous	0
system	0
to	0
facilitate	0
reflex	0
bradycardia	3
mediated	0
through	0
baroreceptor	0
reflexes	0
in	0
response	0
to	0
an	0
acute	0
increase	0
in	0
arterial	0
pressure	0
.	0

Initial	0
potassium	1
loss	0
and	0
hypokalaemia	3
during	0
chlorthalidone	1
administration	0
in	0
patients	0
with	0
essential	0
hypertension	3
:	0
the	0
influence	0
of	0
dietary	0
sodium	1
restriction	0
.	0

To	0
investigate	0
the	0
initial	0
potassium	1
loss	0
and	0
development	0
of	0
hypokalaemia	3
during	0
the	0
administration	0
of	0
an	0
oral	0
diuretic	0
,	0
metabolic	0
balance	0
studies	0
were	0
performed	0
in	0
ten	0
patients	0
with	0
essential	0
hypertension	3
who	0
had	0
shown	0
hypokalaemia	3
under	0
prior	0
oral	0
diuretic	0
treatment	0
.	0

Chlorthalidone	1
(	0
50	0
mg	0
daily	0
)	0
was	0
given	0
for	0
14	0
days	0
.	0

Six	0
patients	0
received	0
a	0
normal	0
-	0
sodium	1
diet	0
and	0
four	0
a	0
low	0
-	0
sodium	1
(	0
17	0
mmol	0
/	0
day	0
)	0
diet	0
.	0

All	0
patients	0
had	0
a	0
normal	0
initial	0
total	0
body	0
potassium	1
(	0
40K	0
)	0
.	0

The	0
electrolyte	0
balances	0
,	0
weight	0
,	0
bromide	0
space	0
,	0
plasma	0
renin	0
activity	0
,	0
and	0
aldosterone	1
secretion	0
rate	0
were	0
measured	0
.	0

In	0
both	0
groups	0
a	0
potassium	1
deficit	0
developed	0
,	0
with	0
proportionally	0
larger	0
losses	0
from	0
the	0
extracellular	0
than	0
from	0
the	0
intracellular	0
compartment	0
.	0

In	0
the	0
normal	0
-	0
sodium	1
group	0
the	0
highest	0
mean	0
potassium	1
deficit	0
was	0
176	0
mmol	0
on	0
day	0
9	0
,	0
after	0
which	0
some	0
potassium	1
was	0
regained	0
;	0
in	0
the	0
low	0
-	0
sodium	1
group	0
the	0
highest	0
deficit	0
was	0
276	0
mmol	0
on	0
day	0
13	0
.	0

The	0
normal	0
-	0
sodium	1
group	0
showed	0
an	0
immediate	0
but	0
temporary	0
rise	0
of	0
the	0
renin	0
and	0
aldosterone	1
levels	0
;	0
in	0
the	0
low	0
-	0
sodium	1
group	0
renin	0
and	0
aldosterone	1
increased	0
more	0
slowly	0
but	0
remained	0
elevated	0
.	0

It	0
is	0
concluded	0
that	0
dietary	0
sodium	1
restriction	0
increases	0
diuretic	0
-	0
induced	0
potassium	1
loss	0
,	0
presumably	0
by	0
an	0
increased	0
activity	0
of	0
the	0
renin	0
-	0
angiotensin	1
-	0
aldosterone	1
system	0
,	0
while	0
sodium	1
delivery	0
to	0
the	0
distal	0
renal	0
tubules	0
remains	0
sufficiently	0
high	0
to	0
allow	0
increased	0
potassium	1
secretion	0
.	0

Reversal	0
of	0
neuroleptic	0
-	0
induced	0
catalepsy	3
by	0
novel	0
aryl	1
-	2
piperazine	2
anxiolytic	0
drugs	0
.	0

The	0
novel	0
anxiolytic	0
drug	0
,	0
buspirone	1
,	0
reverses	0
catalepsy	3
induced	0
by	0
haloperidol	1
.	0

A	0
series	0
of	0
aryl	1
-	2
piperazine	2
analogues	0
of	0
buspirone	1
and	0
other	0
5	1
-	2
hydroxytryptaminergic	2
agonists	2
were	0
tested	0
for	0
their	0
ability	0
to	0
reverse	0
haloperidol	1
induced	0
catalepsy	3
.	0

Those	0
drugs	0
with	0
strong	0
affinity	0
for	0
5	1
-	2
hydroxytryptamine1a	2
receptors	0
were	0
able	0
to	0
reverse	0
catalepsy	3
.	0

Drugs	0
with	0
affinity	0
for	0
other	0
5	1
-	2
HT	2
receptors	0
or	0
weak	0
affinity	0
were	0
ineffective	0
.	0

However	0
,	0
inhibition	0
of	0
postsynaptic	0
5	1
-	2
HT	2
receptors	0
neither	0
inhibited	0
nor	0
potentiated	0
reversal	0
of	0
catalepsy	3
and	0
leaves	0
open	0
the	0
question	0
as	0
to	0
the	0
site	0
or	0
mechanism	0
for	0
this	0
effect	0
.	0

Glycopyrronium	1
requirements	0
for	0
antagonism	0
of	0
the	0
muscarinic	0
side	0
effects	0
of	0
edrophonium	1
.	0

We	0
have	0
compared	0
,	0
in	0
60	0
adult	0
patients	0
,	0
the	0
cardiovascular	0
effects	0
of	0
glycopyrronium	1
5	0
micrograms	0
kg	0
-	0
1	0
and	0
10	0
micrograms	0
kg	0
-	0
1	0
given	0
either	0
simultaneously	0
or	0
1	0
min	0
before	0
edrophonium	1
1	0
mg	0
kg	0
-	0
1	0
.	0

Significant	0
differences	0
between	0
the	0
four	0
groups	0
were	0
detected	0
(	0
P	0
less	0
than	0
0	0
.	0
001	0
)	0
.	0

Both	0
groups	0
receiving	0
10	0
micrograms	0
kg	0
-	0
1	0
showed	0
increases	0
in	0
heart	0
rate	0
of	0
up	0
to	0
30	0
beat	0
min	0
-	0
1	0
(	0
95	0
%	0
confidence	0
limits	0
28	0
-	0
32	0
beat	0
min	0
-	0
1	0
)	0
.	0

Use	0
of	0
glycopyrronium	1
5	0
micrograms	0
kg	0
-	0
1	0
provided	0
greater	0
cardiovascular	0
stability	0
and	0
,	0
given	0
1	0
min	0
before	0
the	0
edrophonium	1
,	0
was	0
sufficient	0
to	0
minimize	0
early	0
,	0
edrophonium	1
-	0
induced	0
bradycardias	3
.	0

This	0
low	0
dose	0
of	0
glycopyrronium	1
provided	0
good	0
control	0
of	0
oropharyngeal	0
secretions	0
.	0

Selective	0
injection	0
of	0
iopentol	1
,	0
iohexol	1
and	0
metrizoate	1
into	0
the	0
left	0
coronary	0
artery	0
of	0
the	0
dog	0
.	0

Induction	0
of	0
ventricular	3
fibrillation	4
and	0
decrease	0
of	0
aortic	0
pressure	0
.	0

In	0
twenty	0
beagle	0
dogs	0
selective	0
injections	0
were	0
made	0
into	0
the	0
left	0
coronary	0
artery	0
with	0
iopentol	1
,	0
iohexol	1
and	0
metrizoate	1
in	0
doses	0
of	0
4	0
ml	0
,	0
8	0
ml	0
and	0
16	0
ml	0
.	0

Thirty	0
-	0
six	0
iopentol	1
injections	0
,	0
35	0
iohexol	1
injections	0
and	0
37	0
metrizoate	1
injections	0
were	0
made	0
.	0

Frequencies	0
of	0
ventricular	3
fibrillation	4
were	0
significantly	0
lower	0
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
after	0
iopentol	1
(	0
0	0
%	0
)	0
and	0
iohexol	1
(	0
3	0
%	0
)	0
than	0
after	0
metrizoate	1
(	0
22	0
%	0
)	0
.	0

Iopentol	1
and	0
iohexol	1
also	0
produced	0
significantly	0
less	0
decrease	0
in	0
aortic	0
blood	0
pressure	0
than	0
metrizoate	1
at	0
the	0
different	0
doses	0
.	0

Thyroid	0
function	0
and	0
urine	0
-	0
concentrating	0
ability	0
during	0
lithium	1
treatment	0
.	0

It	0
has	0
been	0
suggested	0
that	0
adenylate	0
cyclase	0
inhibition	0
may	0
be	0
important	0
in	0
the	0
development	0
of	0
both	0
nephrogenic	3
diabetes	4
insipidus	4
and	0
hypothyroidism	3
during	0
lithium	1
treatment	0
.	0

We	0
measured	0
serum	0
thyroxine	1
and	0
urine	0
-	0
concentrating	0
ability	0
(	0
Umax	0
)	0
in	0
response	0
to	0
desmopressin	0
(	0
DDAVP	0
)	0
in	0
85	0
patients	0
receiving	0
lithium	1
.	0

Hypothyroidism	3
developed	0
in	0
eight	0
patients	0
while	0
they	0
were	0
taking	0
lithium	1
.	0

Impaired	0
Umax	0
was	0
found	0
in	0
both	0
euthyroid	0
and	0
hypothyroid	3
patients	0
while	0
some	0
hypothyroid	3
patients	0
concentrated	0
their	0
urine	0
well	0
.	0

It	0
is	0
concluded	0
that	0
the	0
dominant	0
mechanisms	0
by	0
which	0
lithium	1
exerts	0
these	0
two	0
effects	0
are	0
different	0
.	0

Remodelling	0
of	0
nerve	0
structure	0
in	0
experimental	0
isoniazid	1
neuropathy	3
in	0
the	0
rat	0
.	0

The	0
neuropathy	3
caused	0
by	0
a	0
single	0
dose	0
of	0
isoniazid	1
in	0
rats	0
was	0
studied	0
with	0
a	0
computer	0
-	0
assisted	0
morphometric	0
method	0
.	0

Scatter	0
diagrams	0
of	0
the	0
g	0
ratio	0
(	0
quotient	0
fibre	0
diameter	0
/	0
axon	0
diameter	0
)	0
define	0
regenerating	0
fibres	0
as	0
a	0
distinct	0
population	0
,	0
distinguishable	0
from	0
the	0
surviving	0
fibres	0
by	0
reduced	0
sheath	0
thickness	0
and	0
reduced	0
axon	0
calibre	0
.	0

There	0
was	0
also	0
evidence	0
of	0
a	0
subtle	0
direct	0
toxic	0
effect	0
on	0
the	0
entire	0
fibre	0
population	0
,	0
causing	0
axon	0
shrinkage	0
masked	0
by	0
readjustment	0
of	0
the	0
myelin	0
sheath	0
.	0

Multicenter	0
,	0
double	0
-	0
blind	0
,	0
multiple	0
-	0
dose	0
,	0
parallel	0
-	0
groups	0
efficacy	0
and	0
safety	0
trial	0
of	0
azelastine	1
,	0
chlorpheniramine	1
,	0
and	0
placebo	0
in	0
the	0
treatment	0
of	0
spring	3
allergic	4
rhinitis	4
.	0

Azelastine	1
,	0
a	0
novel	0
antiallergic	0
medication	0
,	0
was	0
compared	0
with	0
chlorpheniramine	1
maleate	2
and	0
placebo	0
for	0
efficacy	0
and	0
safety	0
in	0
the	0
treatment	0
of	0
spring	3
allergic	4
rhinitis	4
in	0
a	0
multicenter	0
,	0
double	0
-	0
blind	0
,	0
multiple	0
-	0
dose	0
,	0
parallel	0
-	0
groups	0
study	0
.	0

0ne	0
hundred	0
fifty	0
-	0
five	0
subjects	0
participated	0
.	0

Subjects	0
ranged	0
in	0
age	0
from	0
18	0
to	0
60	0
years	0
of	0
age	0
and	0
had	0
at	0
least	0
a	0
2	0
-	0
year	0
history	0
of	0
spring	3
allergic	4
rhinitis	4
,	0
confirmed	0
by	0
positive	0
skin	0
test	0
to	0
spring	0
aeroallergens	0
.	0

Medications	0
were	0
given	0
four	0
times	0
daily	0
;	0
the	0
azelastine	1
groups	0
received	0
0	0
.	0
5	0
,	0
1	0
.	0
0	0
,	0
or	0
2	0
.	0
0	0
mg	0
in	0
the	0
morning	0
and	0
evening	0
with	0
placebo	0
in	0
the	0
early	0
and	0
late	0
afternoon	0
;	0
the	0
chlorpheniramine	1
group	0
received	0
4	0
.	0
0	0
mg	0
four	0
times	0
daily	0
.	0

Daily	0
subject	0
symptom	0
cards	0
were	0
completed	0
during	0
a	0
screening	0
period	0
to	0
assess	0
pretreatment	0
symptoms	0
and	0
during	0
a	0
4	0
-	0
week	0
treatment	0
period	0
while	0
subjects	0
received	0
study	0
medications	0
.	0

Individual	0
symptoms	0
,	0
total	0
symptoms	0
,	0
and	0
major	0
symptoms	0
were	0
compared	0
to	0
determine	0
efficacy	0
of	0
medication	0
.	0

Elicited	0
,	0
volunteered	0
,	0
and	0
observed	0
adverse	0
experiences	0
were	0
recorded	0
for	0
each	0
subject	0
and	0
compared	0
among	0
groups	0
.	0

Vital	0
signs	0
,	0
body	0
weights	0
,	0
serum	0
chemistry	0
values	0
,	0
complete	0
blood	0
cell	0
counts	0
,	0
urine	0
studies	0
,	0
and	0
electrocardiograms	0
were	0
obtained	0
for	0
each	0
subject	0
and	0
compared	0
among	0
groups	0
.	0

Symptoms	0
relief	0
in	0
the	0
group	0
receiving	0
the	0
highest	0
concentration	0
of	0
azelastine	1
(	0
2	0
.	0
0	0
mg	0
twice	0
daily	0
)	0
was	0
statistically	0
greater	0
than	0
in	0
the	0
placebo	0
group	0
during	0
all	0
weeks	0
of	0
the	0
study	0
.	0

Lower	0
doses	0
of	0
azelastine	1
were	0
statistically	0
more	0
effective	0
than	0
placebo	0
only	0
during	0
portions	0
of	0
the	0
first	0
3	0
weeks	0
of	0
the	0
study	0
.	0

In	0
contrast	0
,	0
although	0
the	0
chlorpheniramine	1
group	0
did	0
have	0
fewer	0
symptoms	0
than	0
the	0
placebo	0
group	0
during	0
the	0
study	0
,	0
the	0
difference	0
never	0
reached	0
statistical	0
significance	0
during	0
any	0
week	0
of	0
the	0
study	0
.	0

There	0
were	0
no	0
serious	0
side	0
effects	0
in	0
any	0
of	0
the	0
treatment	0
groups	0
.	0

Drowsiness	3
and	0
altered	3
taste	4
perception	4
were	0
increased	0
significantly	0
over	0
placebo	0
only	0
in	0
the	0
high	0
-	0
dose	0
azelastine	1
group	0
.	0

Azelastine	1
appears	0
to	0
be	0
a	0
safe	0
,	0
efficacious	0
medication	0
for	0
seasonal	3
allergic	4
rhinitis	4
.	0

Toxicity	3
due	0
to	0
remission	0
inducing	0
drugs	0
in	0
rheumatoid	3
arthritis	4
.	0

Association	0
with	0
HLA	0
-	0
B35	0
and	0
Cw4	0
antigens	0
.	0

Twenty	0
-	0
five	0
patients	0
with	0
rheumatoid	3
arthritis	4
(	0
RA	3
)	0
who	0
developed	0
toxicity	3
while	0
taking	0
remission	0
inducing	0
drugs	0
and	0
30	0
without	0
toxicity	3
were	0
studied	0
for	0
possible	0
associations	0
with	0
class	0
I	0
and	0
II	0
HLA	0
antigens	0
.	0

A	0
strong	0
association	0
has	0
been	0
found	0
between	0
nephritis	3
and	0
dermatitis	3
due	0
to	0
Tiopronin	1
(	0
a	0
D	1
-	2
Penicillamine	2
like	0
compound	0
)	0
and	0
class	0
I	0
antigens	0
B35	0
-	0
Cw4	0
,	0
and	0
between	0
dermatitis	3
due	0
to	0
gold	1
thiosulphate	1
and	0
B35	0
.	0

Compared	0
to	0
healthy	0
controls	0
a	0
lower	0
DR5	0
frequency	0
was	0
observed	0
in	0
patients	0
with	0
RA	3
except	0
for	0
the	0
Tiopronin	1
related	0
nephritis	3
group	0
.	0

Transient	0
contralateral	3
rotation	4
following	0
unilateral	0
substantia	3
nigra	4
lesion	4
reflects	0
susceptibility	0
of	0
the	0
nigrostriatal	0
system	0
to	0
exhaustion	0
by	0
amphetamine	1
.	0

Following	0
unilateral	0
6	1
-	2
0HDA	2
induced	0
SN	3
lesion	4
,	0
a	0
transient	0
period	0
of	0
contralateral	3
rotation	4
has	0
been	0
reported	0
to	0
precede	0
the	0
predominant	0
ipsilateral	3
circling	4
.	0

In	0
order	0
to	0
clarify	0
the	0
nature	0
of	0
this	0
initial	0
contralateral	3
rotation	4
we	0
examined	0
the	0
effect	0
of	0
the	0
duration	0
of	0
recovery	0
period	0
after	0
the	0
lesion	0
,	0
on	0
amphetamine	1
-	0
induced	0
rotational	3
behavior	4
.	0

Three	0
days	0
post	0
lesion	0
,	0
most	0
rats	0
circled	0
predominantly	0
contralaterally	0
to	0
the	0
lesion	0
.	0

Such	0
contralateral	3
rotation	4
may	0
result	0
from	0
either	0
degeneration	0
-	0
induced	0
breakdown	0
of	0
the	0
DA	0
pool	0
,	0
or	0
lesion	0
-	0
induced	0
increase	0
of	0
DA	0
turnover	0
in	0
the	0
spared	0
neurons	0
.	0

A	0
substantial	0
degree	0
of	0
contralateral	0
preference	0
was	0
still	0
evident	0
when	0
amphetamine	1
was	0
administered	0
for	0
the	0
first	0
time	0
24	0
days	0
after	0
lesioning	0
,	0
indicating	0
involvement	0
of	0
spared	0
cells	0
in	0
the	0
contralateral	3
rotation	4
.	0

However	0
,	0
regardless	0
of	0
the	0
duration	0
of	0
recovery	0
(	0
and	0
irrespective	0
of	0
either	0
lesion	0
volume	0
,	0
amphetamine	1
dose	0
,	0
or	0
post	0
-	0
lesion	0
motor	0
exercise	0
)	0
,	0
amphetamine	1
-	0
induced	0
rotation	3
tended	0
to	0
become	0
gradually	0
more	0
ipsilateral	0
as	0
the	0
observation	0
session	0
progressed	0
,	0
and	0
all	0
rats	0
circled	0
ipsilaterally	0
to	0
the	0
lesion	0
in	0
response	0
to	0
further	0
amphetamine	1
injections	0
.	0

These	0
findings	0
suggest	0
that	0
amphetamine	1
has	0
an	0
irreversible	0
effect	0
on	0
the	0
post	0
-	0
lesion	0
DA	0
pool	0
contributing	0
to	0
contralateral	3
rotation	4
.	0

Mitomycin	1
C	2
associated	0
hemolytic	3
uremic	4
syndrome	4
.	0

Mitomycin	1
C	2
associated	0
Hemolytic	3
Uremic	4
Syndrome	4
(	0
HUS	3
)	0
is	0
a	0
potentially	0
fatal	0
but	0
uncommon	0
condition	0
that	0
is	0
not	0
yet	0
widely	0
recognised	0
.	0

It	0
consists	0
of	0
microangiopathic	0
hemolytic	3
anemia	4
,	0
thrombocytopenia	3
and	0
progressive	0
renal	3
failure	4
associated	0
with	0
mitomycin	1
C	2
treatment	0
and	0
affects	0
about	0
10	0
%	0
of	0
patients	0
treated	0
with	0
this	0
agent	0
.	0

The	0
renal	3
failure	4
usually	0
develops	0
about	0
8	0
-	0
10	0
mth	0
after	0
start	0
of	0
mitomycin	1
C	2
treatment	0
and	0
the	0
mortality	0
is	0
approximately	0
60	0
%	0
from	0
renal	3
failure	4
or	0
pulmonary	3
edema	4
.	0

Renal	3
lesions	4
are	0
similar	0
to	0
those	0
seen	0
in	0
idiopathic	0
HUS	3
and	0
include	0
arteriolar	0
fibrin	0
thrombi	3
,	0
expanded	0
subendothelial	0
zones	0
in	0
glomerular	0
capillary	0
walls	0
,	0
ischemic	3
wrinkling	0
of	0
glomerular	0
basement	0
membranes	0
and	0
mesangiolysis	0
.	0

The	0
mechanism	0
of	0
action	0
is	0
postulated	0
as	0
mitomycin	1
C	2
-	0
induced	0
endothelial	0
cell	0
damage	0
.	0

We	0
describe	0
the	0
clinical	0
course	0
and	0
pathological	0
findings	0
in	0
a	0
65	0
yr	0
-	0
old	0
man	0
with	0
gastric	3
adenocarcinoma	4
who	0
developed	0
renal	3
failure	4
and	0
thrombocytopenia	3
while	0
on	0
treatment	0
with	0
mitomycin	1
C	2
and	0
died	0
in	0
pulmonary	3
edema	4
.	0

Ketanserin	1
pretreatment	0
reverses	0
alfentanil	1
-	0
induced	0
muscle	3
rigidity	4
.	0

Systemic	0
pretreatment	0
with	0
ketanserin	1
,	0
a	0
relatively	0
specific	0
type	0
-	0
2	0
serotonin	1
receptor	0
antagonist	0
,	0
significantly	0
attenuated	0
the	0
muscle	3
rigidity	4
produced	0
in	0
rats	0
by	0
the	0
potent	0
short	0
-	0
acting	0
opiate	0
agonist	0
alfentanil	1
.	0

Following	0
placement	0
of	0
subcutaneous	0
electrodes	0
in	0
each	0
animal	0
'	0
s	0
left	0
gastrocnemius	0
muscle	0
,	0
rigidity	3
was	0
assessed	0
by	0
analyzing	0
root	0
-	0
mean	0
-	0
square	0
electromyographic	0
activity	0
.	0

Intraperitoneal	0
ketanserin	1
administration	0
at	0
doses	0
of	0
0	0
.	0
63	0
and	0
2	0
.	0
5	0
mg	0
/	0
kg	0
prevented	0
the	0
alfentanil	1
-	0
induced	0
increase	0
in	0
electromyographic	0
activity	0
compared	0
with	0
animals	0
pretreated	0
with	0
saline	0
.	0

Chlordiazepoxide	1
at	0
doses	0
up	0
to	0
10	0
mg	0
/	0
kg	0
failed	0
to	0
significantly	0
influence	0
the	0
rigidity	3
produced	0
by	0
alfentanil	1
.	0

Despite	0
the	0
absence	0
of	0
rigidity	3
,	0
animals	0
that	0
received	0
ketanserin	1
(	0
greater	0
than	0
0	0
.	0
31	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
followed	0
by	0
alfentanil	1
were	0
motionless	0
,	0
flaccid	0
,	0
and	0
less	0
responsive	0
to	0
external	0
stimuli	0
than	0
were	0
animals	0
receiving	0
alfentanil	1
alone	0
.	0

Rats	0
that	0
received	0
ketanserin	1
and	0
alfentanil	1
exhibited	0
less	0
rearing	0
and	0
exploratory	0
behavior	0
at	0
the	0
end	0
of	0
the	0
60	0
-	0
min	0
recording	0
period	0
than	0
did	0
animals	0
that	0
received	0
ketanserin	1
alone	0
.	0

These	0
results	0
,	0
in	0
combination	0
with	0
previous	0
work	0
,	0
suggest	0
that	0
muscle	3
rigidity	4
,	0
a	0
clinically	0
relevant	0
side	0
-	0
effect	0
of	0
parenteral	0
narcotic	0
administration	0
,	0
may	0
be	0
partly	0
mediated	0
via	0
serotonergic	0
pathways	0
.	0

Pretreatment	0
with	0
type	0
-	0
2	0
serotonin	1
antagonists	0
may	0
be	0
clinically	0
useful	0
in	0
attenuating	0
opiate	0
-	0
induced	0
rigidity	3
,	0
although	0
further	0
studies	0
will	0
be	0
necessary	0
to	0
assess	0
the	0
interaction	0
of	0
possibly	0
enhanced	0
CNS	0
,	0
cardiovascular	3
,	4
and	4
respiratory	4
depression	4
.	0

Antagonism	0
of	0
diazepam	1
-	0
induced	0
sedative	0
effects	0
by	0
Ro15	1
-	2
1788	2
in	0
patients	0
after	0
surgery	0
under	0
lumbar	0
epidural	0
block	0
.	0

A	0
double	0
-	0
blind	0
placebo	0
-	0
controlled	0
investigation	0
of	0
efficacy	0
and	0
safety	0
.	0

The	0
aim	0
of	0
this	0
study	0
was	0
to	0
assess	0
the	0
efficacy	0
of	0
Ro15	1
-	2
1788	2
and	0
a	0
placebo	0
in	0
reversing	0
diazepam	1
-	0
induced	0
effects	0
after	0
surgery	0
under	0
epidural	0
block	0
,	0
and	0
to	0
evaluate	0
the	0
local	0
tolerance	0
and	0
general	0
safety	0
of	0
Ro15	1
-	2
1788	2
.	0

Fifty	0
-	0
seven	0
patients	0
were	0
sedated	0
with	0
diazepam	1
for	0
surgery	0
under	0
epidural	0
anaesthesia	0
.	0

Antagonism	0
of	0
diazepam	1
-	0
induced	0
effects	0
by	0
Ro15	1
-	2
1788	2
was	0
investigated	0
postoperatively	0
in	0
a	0
double	0
-	0
blind	0
placebo	0
-	0
controlled	0
trial	0
.	0

The	0
patient	0
'	0
s	0
subjective	0
assessment	0
of	0
mood	0
rating	0
,	0
an	0
objective	0
test	0
of	0
performance	0
,	0
a	0
test	0
for	0
amnesia	3
,	0
and	0
vital	0
signs	0
were	0
recorded	0
for	0
up	0
to	0
300	0
min	0
after	0
administration	0
of	0
the	0
trial	0
drug	0
.	0

No	0
significant	0
differences	0
between	0
the	0
two	0
groups	0
were	0
observed	0
for	0
mood	0
rating	0
,	0
amnesia	3
,	0
or	0
vital	0
signs	0
.	0

The	0
Ro15	1
-	2
1788	2
group	0
showed	0
a	0
significant	0
improvement	0
in	0
the	0
performance	0
test	0
up	0
to	0
120	0
min	0
after	0
administration	0
of	0
the	0
drug	0
.	0

There	0
was	0
no	0
evidence	0
of	0
reaction	0
at	0
the	0
injection	0
site	0
.	0

Chorea	3
associated	0
with	0
oral	1
contraception	2
.	0

Three	0
patients	0
developed	0
chorea	3
while	0
receiving	0
oral	1
contraceptives	2
.	0

Two	0
were	0
young	0
patients	0
whose	0
chorea	3
developed	0
long	0
after	0
treatment	0
had	0
been	0
started	0
and	0
disappeared	0
soon	0
after	0
it	0
had	0
been	0
discontinued	0
.	0

The	0
third	0
patient	0
had	0
acute	0
amphetamine	1
-	0
induced	0
chorea	3
after	0
prolonged	0
oral	1
contraception	2
.	0

Prolonged	0
administration	0
of	0
female	0
sex	0
hormones	0
is	0
a	0
possible	0
cause	0
of	0
chorea	3
in	0
women	0
who	0
have	0
not	0
previously	0
had	0
chorea	3
or	0
rheumatic	3
fever	4
.	0

Co	0
-	0
carcinogenic	3
effect	0
of	0
retinyl	1
acetate	2
on	0
forestomach	3
carcinogenesis	4
of	0
male	0
F344	0
rats	0
induced	0
with	0
butylated	1
hydroxyanisole	2
.	0

The	0
potential	0
modifying	0
effect	0
of	0
retinyl	1
acetate	2
(	0
RA	1
)	0
on	0
butylated	1
hydroxyanisole	2
(	0
BHA	1
)	0
-	0
induced	0
rat	0
forestomach	3
tumorigenesis	4
was	0
examined	0
.	0

Male	0
F344	0
rats	0
,	0
5	0
weeks	0
of	0
age	0
,	0
were	0
maintained	0
on	0
diet	0
containing	0
1	0
%	0
or	0
2	0
%	0
BHA	1
by	0
weight	0
and	0
simultaneously	0
on	0
drinking	0
water	0
supplemented	0
with	0
RA	1
at	0
various	0
concentrations	0
(	0
w	0
/	0
v	0
)	0
for	0
52	0
weeks	0
.	0

In	0
groups	0
given	0
2	0
%	0
BHA	1
,	0
although	0
marked	0
hyperplastic	0
changes	0
of	0
the	0
forestomach	0
epithelium	0
were	0
observed	0
in	0
all	0
animals	0
,	0
co	0
-	0
administration	0
of	0
0	0
.	0
25	0
%	0
RA	1
significantly	0
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
increased	0
the	0
incidence	0
of	0
forestomach	3
tumors	4
(	0
squamous	3
cell	4
papilloma	4
and	0
carcinoma	3
)	0
to	0
60	0
%	0
(	0
9	0
/	0
15	0
,	0
2	0
rats	0
with	0
carcinoma	3
)	0
from	0
15	0
%	0
(	0
3	0
/	0
20	0
,	0
one	0
rat	0
with	0
carcinoma	3
)	0
in	0
the	0
group	0
given	0
RA	1
-	0
free	0
water	0
.	0

In	0
rats	0
given	0
1	0
%	0
BHA	1
,	0
RA	1
co	0
-	0
administered	0
at	0
a	0
dose	0
of	0
0	0
.	0
05	0
,	0
0	0
.	0
1	0
,	0
0	0
.	0
2	0
or	0
0	0
.	0
25	0
%	0
showed	0
a	0
dose	0
-	0
dependent	0
enhancing	0
effect	0
on	0
the	0
development	0
of	0
the	0
BHA	1
-	0
induced	0
epithelial	3
hyperplasia	4
.	0

Tumors	3
,	0
all	0
papillomas	3
,	0
were	0
induced	0
in	0
3	0
rats	0
(	0
17	0
%	0
)	0
with	0
0	0
.	0
25	0
%	0
RA	1
and	0
in	0
one	0
rat	0
(	0
10	0
%	0
)	0
with	0
0	0
.	0
05	0
%	0
RA	1
co	0
-	0
administration	0
.	0

RA	1
alone	0
did	0
not	0
induce	0
hyperplastic	0
changes	0
in	0
the	0
forestomach	0
.	0

These	0
findings	0
indicate	0
that	0
RA	1
acted	0
as	0
a	0
co	0
-	0
carcinogen	0
in	0
the	0
BHA	1
forestomach	3
carcinogenesis	4
of	0
the	0
rat	0
.	0

A	0
prospective	0
study	0
on	0
the	0
dose	0
dependency	0
of	0
cardiotoxicity	3
induced	0
by	0
mitomycin	1
C	2
.	0

Since	0
1975	0
mitomycin	1
C	2
(	0
MMC	1
)	0
has	0
been	0
suggested	0
to	0
be	0
cardiotoxic	3
,	0
especially	0
when	0
combined	0
with	0
or	0
given	0
following	0
doxorubicin	1
.	0

Data	0
on	0
dose	0
dependency	0
or	0
incidence	0
concerning	0
this	0
side	0
effect	0
were	0
not	0
known	0
.	0

We	0
have	0
initiated	0
a	0
prospective	0
study	0
to	0
obtain	0
some	0
more	0
data	0
on	0
these	0
subjects	0
.	0

Forty	0
-	0
four	0
MMC	1
-	0
treated	0
patients	0
were	0
studied	0
,	0
37	0
of	0
them	0
could	0
be	0
evaluated	0
.	0

All	0
patients	0
were	0
studied	0
by	0
repeated	0
physical	0
examinations	0
,	0
chest	0
X	0
-	0
rays	0
,	0
electro	0
-	0
and	0
echocardiography	0
and	0
radionuclide	0
left	0
ventricular	0
ejection	0
fraction	0
(	0
EF	0
)	0
determinations	0
.	0

The	0
results	0
were	0
evaluated	0
per	0
cumulative	0
dose	0
level	0
.	0

0ne	0
of	0
the	0
patients	0
developed	0
cardiac	3
failure	4
after	0
30	0
mg	0
m	0
-	0
2	0
MMC	1
and	0
only	0
150	0
mg	0
m	0
-	0
2	0
doxorubicin	1
.	0

The	0
cardiac	3
failure	4
was	0
predicted	0
by	0
a	0
drop	0
in	0
EF	0
determined	0
during	0
a	0
cold	0
pressor	0
test	0
.	0

None	0
of	0
the	0
other	0
patients	0
developed	0
clinical	0
cardiotoxicity	3
,	0
nor	0
did	0
the	0
studied	0
parameters	0
change	0
.	0

The	0
literature	0
on	0
this	0
subject	0
was	0
also	0
reviewed	0
.	0

Based	0
on	0
the	0
combined	0
data	0
from	0
the	0
present	0
study	0
and	0
the	0
literature	0
,	0
we	0
suggest	0
that	0
MMC	1
-	0
related	0
cardiotoxicity	3
is	0
dose	0
dependent	0
,	0
occurring	0
at	0
cumulative	0
dose	0
levels	0
of	0
30	0
mg	0
m	0
-	0
2	0
or	0
more	0
,	0
mainly	0
in	0
patients	0
also	0
(	0
previously	0
or	0
simultaneously	0
)	0
treated	0
with	0
doxorubicin	1
.	0

The	0
incidence	0
is	0
likely	0
to	0
be	0
less	0
than	0
10	0
%	0
even	0
for	0
this	0
risk	0
group	0
.	0

Reversible	0
cerebral	3
lesions	4
associated	0
with	0
tiazofurin	1
usage	0
:	0
MR	0
demonstration	0
.	0

Tiazofurin	1
is	0
an	0
experimental	0
chemotherapeutic	0
agent	0
currently	0
undergoing	0
clinical	0
evaluation	0
.	0

We	0
report	0
our	0
results	0
with	0
magnetic	0
resonance	0
(	0
MR	0
)	0
in	0
demonstrating	0
reversible	0
cerebral	3
abnormalities	4
concurrent	0
with	0
the	0
use	0
of	0
this	0
drug	0
.	0

The	0
abnormalities	0
on	0
MR	0
were	0
correlated	0
with	0
findings	0
on	0
CT	0
as	0
well	0
as	0
with	0
cerebral	0
angiography	0
.	0

The	0
utility	0
of	0
MR	0
in	0
the	0
evaluation	0
of	0
patients	0
receiving	0
this	0
new	0
agent	0
is	0
illustrated	0
.	0

Receptor	0
mechanisms	0
of	0
nicotine	1
-	0
induced	0
locomotor	3
hyperactivity	4
in	0
chronic	0
nicotine	1
-	0
treated	0
rats	0
.	0

Rats	0
were	0
pretreated	0
with	0
saline	0
or	0
nicotine	1
(	0
1	0
.	0
5	0
mg	0
/	0
kg	0
per	0
day	0
)	0
by	0
subcutaneously	0
implanting	0
each	0
animal	0
with	0
an	0
Alzet	0
osmotic	0
mini	0
-	0
pump	0
which	0
continuously	0
released	0
saline	0
or	0
nicotine	1
for	0
1	0
,	0
5	0
and	0
14	0
days	0
.	0

At	0
the	0
end	0
of	0
each	0
pretreatment	0
period	0
,	0
animals	0
were	0
used	0
for	0
(	0
i	0
)	0
determining	0
their	0
locomotor	0
response	0
to	0
acutely	0
injected	0
nicotine	1
(	0
0	0
.	0
2	0
mg	0
/	0
kg	0
,	0
s	0
.	0
c	0
.	0
)	0
and	0
(	0
ii	0
)	0
measuring	0
the	0
density	0
of	0
L	0
-	0
[	0
3H	0
]	0
nicotine	1
and	0
[	0
3H	0
]	0
spiperone	1
binding	0
sites	0
in	0
the	0
striatum	0
.	0

We	0
observed	0
no	0
changes	0
in	0
nicotine	1
-	0
induced	0
locomotor	0
response	0
,	0
striatal	0
L	0
-	0
[	0
3H	0
]	0
nicotine	1
and	0
[	0
3H	0
]	0
spiperone	1
binding	0
in	0
the	0
animals	0
pretreated	0
with	0
nicotine	1
for	0
1	0
day	0
.	0

In	0
rats	0
which	0
were	0
pretreated	0
with	0
nicotine	1
for	0
5	0
days	0
,	0
there	0
was	0
a	0
significant	0
increase	0
in	0
the	0
nicotine	1
-	0
stimulated	0
locomotor	0
response	0
which	0
was	0
associated	0
with	0
an	0
increase	0
in	0
the	0
number	0
of	0
L	0
-	0
[	0
3H	0
]	0
nicotine	1
binding	0
sites	0
and	0
also	0
with	0
an	0
elevated	0
dopamine	1
(	0
DA	1
)	0
level	0
in	0
the	0
striatum	0
.	0

The	0
number	0
of	0
striatal	0
[	0
3H	0
]	0
spiperone	1
binding	0
sites	0
was	0
not	0
affected	0
.	0

In	0
animals	0
pretreated	0
with	0
nicotine	1
for	0
14	0
days	0
,	0
the	0
nicotine	1
-	0
induced	0
locomotor	0
response	0
remained	0
to	0
be	0
potentiated	0
.	0

However	0
,	0
this	0
response	0
was	0
correlated	0
with	0
an	0
elevated	0
number	0
of	0
striatal	0
[	0
3H	0
]	0
spiperone	1
binding	0
sites	0
,	0
whereas	0
the	0
number	0
of	0
striatal	0
L	0
-	0
[	0
3H	0
]	0
nicotine	1
binding	0
sites	0
and	0
the	0
striatal	0
DA	1
level	0
were	0
normal	0
.	0

These	0
results	0
suggest	0
that	0
chronic	0
nicotine	1
-	0
treated	0
rats	0
develop	0
locomotor	3
hyperactivity	4
in	0
response	0
to	0
nicotine	1
initially	0
due	0
to	0
increases	0
of	0
both	0
the	0
density	0
of	0
nicotinic	0
receptors	0
and	0
DA	1
concentration	0
,	0
followed	0
by	0
inducing	0
DA	1
receptor	0
supersensitivity	0
in	0
the	0
striatum	0
.	0

Amelioration	0
of	0
bendrofluazide	1
-	0
induced	0
hypokalemia	3
by	0
timolol	1
.	0

The	0
beta	0
adrenergic	0
blocking	0
drug	0
,	0
timolol	1
,	0
tended	0
to	0
correct	0
the	0
hypokalemia	3
of	0
short	0
-	0
term	0
bendrofluazide	1
treatment	0
in	0
6	0
healthy	0
male	0
subjects	0
and	0
although	0
the	0
effect	0
was	0
small	0
it	0
was	0
significant	0
.	0

Timolol	1
also	0
reduced	0
the	0
rise	0
in	0
plasma	0
aldosterone	1
and	0
urine	0
potassium	1
excretion	0
following	0
bendrofluazide	1
and	0
increased	0
the	0
urine	0
sodium	1
/	0
potassium	1
ratio	0
.	0

There	0
was	0
no	0
evidence	0
of	0
a	0
shift	0
of	0
potassium	1
from	0
the	0
intracellular	0
to	0
the	0
extracellular	0
space	0
.	0

St	3
.	4

Anthony	3
'	4
s	4
fire	4
,	0
then	0
and	0
now	0
:	0
a	0
case	0
report	0
and	0
historical	0
review	0
.	0

A	0
rare	0
case	0
of	0
morbid	0
vasospasm	3
,	0
together	0
with	0
striking	0
angiographic	0
findings	0
,	0
is	0
described	0
secondary	0
to	0
the	0
ingestion	0
of	0
methysergide	1
by	0
a	0
48	0
-	0
year	0
-	0
old	0
woman	0
.	0

A	0
brief	0
review	0
of	0
the	0
literature	0
on	0
similar	0
cases	0
is	0
presented	0
.	0

A	0
discussion	0
of	0
the	0
history	0
of	0
ergot	1
includes	0
its	0
original	0
discovery	0
,	0
the	0
epidemics	0
of	0
gangrene	3
that	0
it	0
has	0
caused	0
through	0
the	0
ages	0
and	0
its	0
past	0
and	0
present	0
role	0
in	0
the	0
management	0
of	0
migraine	3
headache	4
.	0

Despite	0
the	0
advent	0
of	0
calcium	1
channel	0
blockers	0
and	0
beta	0
-	0
adrenergic	0
antagonists	0
,	0
ergot	1
preparations	0
continue	0
to	0
play	0
a	0
major	0
role	0
in	0
migraine	3
therapy	0
,	0
so	0
that	0
the	0
danger	0
of	0
St	3
.	4

Anthony	3
'	4
s	4
fire	4
persists	0
.	0

Cardiac	0
transplantation	0
:	0
improved	0
quality	0
of	0
survival	0
with	0
a	0
modified	0
immunosuppressive	0
protocol	0
.	0

The	0
effects	0
on	0
renal	0
function	0
on	0
two	0
different	0
immunosuppressive	0
protocols	0
were	0
evaluated	0
retrospectively	0
in	0
two	0
subsequent	0
groups	0
of	0
heart	0
transplant	0
recipients	0
.	0

In	0
group	0
I	0
,	0
cyclosporine	1
was	0
given	0
before	0
the	0
procedure	0
at	0
a	0
loading	0
dose	0
of	0
17	0
.	0
5	0
mg	0
/	0
kg	0
and	0
then	0
continued	0
after	0
the	0
procedure	0
to	0
keep	0
a	0
whole	0
blood	0
level	0
about	0
1000	0
ng	0
/	0
ml	0
.	0

In	0
group	0
II	0
,	0
cyclosporine	1
was	0
started	0
only	0
after	0
the	0
procedure	0
at	0
a	0
lower	0
dosage	0
and	0
was	0
complemented	0
by	0
azathioprine	1
,	0
which	0
was	0
used	0
for	0
the	0
first	0
postoperative	0
week	0
.	0

Group	0
II	0
showed	0
a	0
better	0
perioperative	0
renal	0
function	0
as	0
determined	0
by	0
serum	0
blood	0
urea	1
nitrogen	2
and	0
serum	0
creatinine	1
levels	0
.	0

Group	0
II	0
also	0
showed	0
a	0
significant	0
decrease	0
of	0
chronic	0
nephrotoxicity	3
secondary	0
to	0
long	0
-	0
term	0
therapy	0
with	0
cyclosporine	1
.	0

Despite	0
this	0
improvement	0
in	0
late	0
renal	0
function	0
,	0
group	0
II	0
still	0
shows	0
a	0
slow	0
rise	0
in	0
serum	0
creatinine	1
.	0

We	0
think	0
that	0
even	0
these	0
lower	0
dosages	0
of	0
cyclosporine	1
can	0
cause	0
chronic	0
nephrotoxicity	3
and	0
that	0
further	0
modification	0
of	0
the	0
immunosuppressive	0
regimen	0
is	0
required	0
to	0
completely	0
abolish	0
this	0
toxic	0
side	0
effect	0
.	0

Ethopropazine	1
and	0
benztropine	1
in	0
neuroleptic	0
-	0
induced	0
parkinsonism	3
.	0

In	0
a	0
12	0
-	0
week	0
controlled	0
study	0
ethopropazine	1
was	0
compared	0
to	0
benztropine	1
in	0
the	0
treatment	0
of	0
parkinsonism	3
induced	0
by	0
fluphenazine	1
enanthate	2
in	0
60	0
schizophrenic	3
outpatients	0
.	0

Ethopropazine	1
and	0
benztropine	1
were	0
found	0
to	0
be	0
equally	0
effective	0
in	0
controlling	0
parkinsonian	3
symptoms	4
and	0
were	0
as	0
efficacious	0
as	0
procyclidine	1
,	0
their	0
previous	0
antiparkinsonian	0
drug	0
.	0

However	0
,	0
benztropine	1
treated	0
patients	0
had	0
a	0
significant	0
increase	0
in	0
tardive	3
dyskinesia	4
compared	0
to	0
their	0
condition	0
during	0
procyclindine	1
treatment	0
,	0
and	0
significantly	0
more	0
anxiety	3
and	0
depression	3
than	0
ethopropazine	1
treated	0
patients	0
.	0

This	0
suggests	0
that	0
benztropine	1
is	0
not	0
the	0
anticholinergic	0
drug	0
of	0
choice	0
in	0
the	0
treatment	0
of	0
neuroleptic	0
-	0
induced	0
parkinsonian	3
symptoms	4
,	0
because	0
of	0
its	0
more	0
toxic	0
central	0
and	0
peripheral	0
atropinic	0
effect	0
.	0

Quinidine	1
phenylethylbarbiturate	2
-	0
induced	0
fulminant	0
hepatitis	3
in	0
a	0
pregnant	0
woman	0
.	0

A	0
case	0
report	0
.	0

We	0
report	0
the	0
case	0
of	0
a	0
19	0
-	0
year	0
-	0
old	0
Laotian	0
patient	0
affected	0
by	0
fulminant	0
hepatitis	3
during	0
the	0
third	0
trimester	0
of	0
her	0
pregnancy	0
after	0
a	0
1	0
-	0
month	0
administration	0
of	0
quinidine	1
phenylethylbarbiturate	2
.	0

After	0
delivery	0
,	0
the	0
patient	0
underwent	0
orthotopic	0
liver	0
transplantation	0
.	0

The	0
patient	0
was	0
in	0
good	0
condition	0
16	0
months	0
after	0
liver	0
transplantation	0
.	0

Quinidine	1
itself	0
or	0
phenylethylbarbiturate	1
may	0
be	0
responsible	0
for	0
fulminant	0
hepatitis	3
in	0
this	0
patient	0
.	0

Mechanisms	0
of	0
myocardial	3
ischemia	4
induced	0
by	0
epinephrine	1
:	0
comparison	0
with	0
exercise	0
-	0
induced	0
ischemia	3
.	0

The	0
role	0
of	0
epinephrine	1
in	0
eliciting	0
myocardial	3
ischemia	4
was	0
examined	0
in	0
patients	0
with	0
coronary	3
artery	4
disease	4
.	0

0bjective	0
signs	0
of	0
ischemia	3
and	0
factors	0
increasing	0
myocardial	0
oxygen	1
consumption	0
were	0
compared	0
during	0
epinephrine	1
infusion	0
and	0
supine	0
bicycle	0
exercise	0
.	0

Both	0
epinephrine	1
and	0
exercise	0
produced	0
myocardial	3
ischemia	4
as	0
evidenced	0
by	0
ST	0
segment	0
depression	3
and	0
angina	3
.	0

However	0
,	0
the	0
mechanisms	0
of	0
myocardial	3
ischemia	4
induced	0
by	0
epinephrine	1
were	0
significantly	0
different	0
from	0
those	0
of	0
exercise	0
.	0

Exercise	0
-	0
induced	0
myocardial	3
ischemia	4
was	0
marked	0
predominantly	0
by	0
increased	0
heart	0
rate	0
and	0
rate	0
-	0
pressure	0
product	0
with	0
a	0
minor	0
contribution	0
of	0
end	0
-	0
diastolic	0
volume	0
,	0
while	0
epinephrine	1
-	0
induced	0
ischemia	3
was	0
characterized	0
by	0
a	0
marked	0
increase	0
in	0
contractility	0
and	0
a	0
less	0
pronounced	0
increase	0
in	0
heart	0
rate	0
and	0
rate	0
-	0
pressure	0
product	0
.	0

These	0
findings	0
indicate	0
that	0
ischemia	3
produced	0
by	0
epinephrine	1
,	0
as	0
may	0
occur	0
during	0
states	0
of	0
emotional	0
distress	0
,	0
has	0
a	0
mechanism	0
distinct	0
from	0
that	0
due	0
to	0
physical	0
exertion	0
.	0

Recent	0
preclinical	0
and	0
clinical	0
studies	0
with	0
the	0
thymidylate	0
synthase	0
inhibitor	0
N10	1
-	2
propargyl	2
-	2
5	2
,	2
8	2
-	2
dideazafolic	2
acid	2
(	0
CB	1
3717	2
)	0
.	0

CB	1
3717	2
,	0
N10	1
-	2
propargyl	2
-	2
5	2
,	2
8	2
-	2
dideazafolic	2
acid	2
,	0
is	0
a	0
tight	0
-	0
binding	0
inhibitor	0
of	0
thymidylate	0
synthase	0
(	0
TS	0
)	0
whose	0
cytotoxicity	3
is	0
mediated	0
solely	0
through	0
the	0
inhibition	0
of	0
this	0
enzyme	0
.	0

Recent	0
preclinical	0
studies	0
have	0
focused	0
on	0
the	0
intracellular	0
formation	0
of	0
CB	1
3717	2
polyglutamates	0
.	0

Following	0
a	0
12	0
-	0
hour	0
exposure	0
of	0
L1210	0
cells	0
to	0
50	0
microM	0
[	0
3H	0
]	0
CB	1
3717	2
,	0
30	0
%	0
of	0
the	0
extractable	0
radioactivity	0
could	0
be	0
accounted	0
for	0
as	0
CB	1
3717	2
tetra	0
-	0
and	0
pentaglutamate	0
,	0
as	0
determined	0
by	0
high	0
-	0
pressure	0
liquid	0
chromatography	0
(	0
HPLC	0
)	0
analyses	0
.	0

As	0
inhibitors	0
of	0
isolated	0
L1210	0
TS	0
,	0
CB	0
3717	0
di	0
-	0
,	0
tri	0
-	0
,	0
tetra	0
-	0
and	0
pentaglutamate	0
are	0
26	0
-	0
,	0
87	0
-	0
,	0
119	0
-	0
and	0
114	0
-	0
fold	0
more	0
potent	0
than	0
CB	1
3717	2
,	0
respectively	0
,	0
and	0
their	0
formation	0
may	0
,	0
therefore	0
,	0
be	0
an	0
important	0
determinant	0
of	0
CB	1
3717	2
cytotoxicity	3
.	0

In	0
early	0
clinical	0
studies	0
with	0
CB	1
3717	2
,	0
activity	0
has	0
been	0
seen	0
in	0
breast	3
cancer	4
,	0
ovarian	3
cancer	4
,	0
hepatoma	3
,	0
and	0
mesothelioma	3
.	0

Toxicities	3
included	0
hepatotoxicity	3
,	0
malaise	3
,	0
and	0
dose	0
-	0
limiting	0
nephrotoxicity	3
.	0

This	0
latter	0
effect	0
is	0
thought	0
to	0
be	0
due	0
to	0
drug	0
precipitation	0
within	0
the	0
renal	0
tubule	0
as	0
a	0
result	0
of	0
the	0
poor	0
solubility	0
of	0
CB	1
3717	2
under	0
acidic	0
conditions	0
.	0

In	0
an	0
attempt	0
to	0
overcome	0
this	0
problem	0
,	0
a	0
clinical	0
trial	0
of	0
CB	1
3717	2
administered	0
with	0
alkaline	0
diuresis	0
is	0
under	0
way	0
.	0

Preliminary	0
results	0
at	0
400	0
and	0
500	0
mg	0
/	0
m2	0
suggest	0
that	0
a	0
reduction	0
in	0
nephrotoxicity	3
may	0
have	0
been	0
achieved	0
with	0
only	0
1	0
instance	0
of	0
renal	3
toxicity	4
in	0
10	0
patients	0
.	0

Hepatotoxicity	3
and	0
malaise	3
are	0
again	0
the	0
most	0
frequent	0
side	0
effects	0
.	0

Evidence	0
of	0
antitumor	0
activity	0
has	0
been	0
seen	0
in	0
3	0
patients	0
.	0

Pharmacokinetic	0
investigations	0
have	0
shown	0
that	0
alkaline	0
diuresis	0
does	0
not	0
alter	0
CB	1
3717	2
plasma	0
levels	0
or	0
urinary	0
excretion	0
and	0
that	0
satisfactory	0
urinary	0
alkalinization	0
can	0
be	0
readily	0
achieved	0
.	0

Type	3
B	4
hepatitis	4
after	0
needle	0
-	0
stick	0
exposure	0
:	0
prevention	0
with	0
hepatitis	3
B	4
immune	0
globulin	0
.	0

Final	0
report	0
of	0
the	0
Veterans	0
Administration	0
Cooperative	0
Study	0
.	0

Hepatitis	3
B	4
immune	0
globulin	0
(	0
HBIG	0
)	0
and	0
immune	0
serum	0
globulin	0
(	0
ISG	0
)	0
were	0
examined	0
in	0
a	0
randomized	0
,	0
double	0
-	0
blind	0
trial	0
to	0
assess	0
their	0
relative	0
efficacies	0
in	0
preventing	0
type	3
B	4
hepatitis	4
after	0
needle	0
-	0
stick	0
exposure	0
to	0
hepatitis	1
B	2
surface	2
antigen	2
(	0
HBsAG	1
)	0
-	0
positive	0
donors	0
.	0

Clinical	0
hepatitis	3
developed	0
in	0
1	0
.	0
4	0
%	0
of	0
HBIG	0
and	0
in	0
5	0
.	0
9	0
%	0
of	0
ISG	0
recipients	0
(	0
P	0
=	0
0	0
.	0
016	0
)	0
,	0
and	0
seroconversion	0
(	0
anti	0
-	0
HBs	0
)	0
occurred	0
in	0
5	0
.	0
6	0
%	0
and	0
20	0
.	0
7	0
%	0
of	0
them	0
respectively	0
(	0
P	0
less	0
than	0
0	0
.	0
001	0
)	0
.	0

Mild	0
and	0
transient	0
side	0
-	0
effects	0
were	0
noted	0
in	0
3	0
.	0
0	0
%	0
of	0
ISG	0
and	0
in	0
3	0
.	0
2	0
%	0
of	0
HBIG	0
recipients	0
.	0

Available	0
donor	0
sera	0
were	0
examined	0
for	0
DNA	0
polymerase	0
(	0
DNAP	0
)	0
and	0
e	0
antigen	0
and	0
antibody	0
(	0
HBeAg	1
;	0
anti	0
-	0
HBE	0
)	0
.	0

Both	0
DNAP	0
and	0
HBeAg	1
showed	0
a	0
highly	0
statistically	0
significant	0
correlation	0
with	0
the	0
infectivity	0
of	0
HBsAg	1
-	0
positive	0
donors	0
.	0

Hepatitis	3
B	4
immune	0
globulin	0
remained	0
significantly	0
superior	0
to	0
ISG	0
in	0
preventing	0
type	3
B	4
hepatitis	4
even	0
when	0
the	0
analysis	0
was	0
confined	0
to	0
these	0
two	0
high	0
-	0
risk	0
subgroups	0
.	0

The	0
efficacy	0
of	0
ISG	0
in	0
preventing	0
type	3
B	4
hepatitis	4
cannot	0
be	0
ascertained	0
because	0
a	0
true	0
placebo	0
group	0
was	0
not	0
included	0
.	0

Production	0
of	0
autochthonous	0
prostate	3
cancer	4
in	0
Lobund	0
-	0
Wistar	0
rats	0
by	0
treatments	0
with	0
N	1
-	2
nitroso	2
-	2
N	2
-	2
methylurea	2
and	0
testosterone	1
.	0

More	0
than	0
50	0
%	0
of	0
Lobund	0
-	0
Wistar	0
(	0
L	0
-	0
W	0
)	0
strain	0
rats	0
developed	0
large	0
,	0
palpable	0
prostate	3
adenocarcinomas	4
(	0
PAs	3
)	0
following	0
treatments	0
with	0
N	1
-	2
nitroso	2
-	2
N	2
-	2
methylurea	2
(	0
CAS	0
:	0
684	0
-	0
93	0
-	0
5	0
)	0
and	0
testosterone	1
propionate	2
[	0
(	0
TP	1
)	0
CAS	0
:	0
57	0
-	0
85	0
-	0
2	0
]	0
,	0
and	0
most	0
of	0
the	0
tumor	3
-	0
bearing	0
rats	0
manifested	0
metastatic	0
lesions	0
.	0

The	0
incubation	0
periods	0
averaged	0
10	0
.	0
6	0
months	0
.	0

Within	0
the	0
same	0
timeframe	0
,	0
no	0
L	0
-	0
W	0
rat	0
developed	0
a	0
similar	0
palpable	0
PA	3
when	0
treated	0
only	0
with	0
TP	1
.	0

In	0
L	0
-	0
W	0
rats	0
,	0
TP	1
acted	0
as	0
a	0
tumor	3
enhancement	0
agent	0
,	0
with	0
primary	0
emphasis	0
on	0
the	0
development	0
of	0
prostate	3
cancer	4
.	0

Relative	0
efficacy	0
and	0
toxicity	3
of	0
netilmicin	1
and	0
tobramycin	1
in	0
oncology	0
patients	0
.	0

We	0
prospectively	0
compared	0
the	0
efficacy	0
and	0
safety	0
of	0
netilmicin	1
sulfate	2
or	0
tobramycin	1
sulfate	2
in	0
conjunction	0
with	0
piperacillin	1
sodium	2
in	0
118	0
immunocompromised	0
patients	0
with	0
presumed	0
severe	0
infections	3
.	0

The	0
two	0
treatment	0
regimens	0
were	0
equally	0
efficacious	0
.	0

Nephrotoxicity	3
occurred	0
in	0
a	0
similar	0
proportion	0
in	0
patients	0
treated	0
with	0
netilmicin	1
and	0
tobramycin	1
(	0
17	0
%	0
vs	0
11	0
%	0
)	0
.	0

0totoxicity	3
occurred	0
in	0
four	0
(	0
9	0
.	0
5	0
%	0
)	0
of	0
42	0
netilmicin	1
and	0
piperacillin	1
and	0
in	0
12	0
(	0
22	0
%	0
)	0
of	0
54	0
tobramycin	1
and	0
piperacillin	1
-	0
treated	0
patients	0
.	0

0f	0
those	0
evaluated	0
with	0
posttherapy	0
audiograms	0
,	0
three	0
of	0
four	0
netilmicin	1
and	0
piperacillin	1
-	0
treated	0
patients	0
had	0
auditory	0
thresholds	0
return	0
to	0
baseline	0
compared	0
with	0
one	0
of	0
nine	0
tobramycin	1
and	0
piperacillin	1
-	0
treated	0
patients	0
.	0

The	0
number	0
of	0
greater	0
than	0
or	0
equal	0
to	0
15	0
-	0
dB	0
increases	0
in	0
auditory	0
threshold	0
as	0
a	0
proportion	0
of	0
total	0
greater	0
than	0
or	0
equal	0
to	0
15	0
-	0
dB	0
changes	0
(	0
increases	0
and	0
decreases	0
)	0
was	0
significantly	0
lower	0
in	0
netilmicin	1
and	0
piperacillin	1
-	0
vs	0
tobramycin	1
and	0
piperacillin	1
-	0
treated	0
patients	0
(	0
18	0
of	0
78	0
vs	0
67	0
of	0
115	0
)	0
.	0

We	0
conclude	0
that	0
aminoglycoside	1
-	0
associated	0
ototoxicity	3
was	0
less	0
severe	0
and	0
more	0
often	0
reversible	0
with	0
netilmicin	1
than	0
with	0
tobramycin	1
.	0

Urinary	0
enzymes	0
and	0
protein	0
patterns	0
as	0
indicators	0
of	0
injury	3
to	4
different	4
regions	4
of	4
the	4
kidney	4
.	0

Acute	3
experimental	4
models	4
of	4
renal	4
damage	4
to	0
the	0
proximal	0
tubular	0
,	0
glomerular	0
,	0
and	0
papillary	0
regions	0
of	0
the	0
rat	0
were	0
produced	0
by	0
administration	0
of	0
hexachloro	1
-	2
1	2
:	2
3	2
-	2
butadiene	2
(	0
HCBD	1
)	0
,	0
puromycin	1
aminonucleoside	2
(	0
PAN	1
)	0
,	0
and	0
2	1
-	2
bromoethylamine	2
(	0
BEA	1
)	0
,	0
respectively	0
.	0

Several	0
routine	0
indicators	0
of	0
nephrotoxicity	3
,	0
the	0
enzymes	0
alkaline	0
phosphatase	0
and	0
N	0
-	0
acetyl	0
-	0
beta	0
-	0
glucosaminidase	0
,	0
and	0
the	0
molecular	0
weight	0
of	0
protein	3
excretion	4
were	0
determined	0
on	0
urine	0
samples	0
.	0

Tubular	0
damage	0
produced	0
by	0
HCBD	1
or	0
BEA	1
was	0
discriminated	0
both	0
quantitatively	0
and	0
qualitatively	0
from	0
glomerular	3
damage	4
produced	0
by	0
PAN	1
.	0

The	0
latter	0
was	0
characterized	0
by	0
a	0
pronounced	0
increase	0
in	0
protein	3
excretion	4
,	0
especially	0
proteins	0
with	0
molecular	0
weight	0
greater	0
than	0
40	0
,	0
000	0
Da	0
.	0

In	0
contrast	0
,	0
protein	3
excretion	4
in	0
tubular	0
damage	0
was	0
raised	0
only	0
slightly	0
and	0
characterized	0
by	0
excretion	3
of	4
proteins	4
of	0
a	0
wide	0
range	0
of	0
molecular	0
weights	0
.	0

Proximal	0
tubular	0
damage	0
caused	0
by	0
HCBD	1
and	0
papillary	0
damage	0
caused	0
by	0
BEA	1
were	0
distinguished	0
both	0
by	0
conventional	0
urinalysis	0
(	0
volume	0
and	0
specific	0
gravity	0
)	0
and	0
by	0
measurement	0
of	0
the	0
two	0
urinary	0
enzymes	0
.	0

Alkaline	0
phosphatase	0
and	0
glucose	1
were	0
markedly	0
and	0
transiently	0
elevated	0
in	0
proximal	0
tubular	0
damage	0
and	0
N	0
-	0
acetyl	0
-	0
beta	0
-	0
glucosaminidase	0
showed	0
a	0
sustained	0
elevation	0
in	0
papillary	0
damage	0
.	0

It	0
is	0
concluded	0
that	0
both	0
selective	0
urinary	0
enzymes	0
and	0
the	0
molecular	0
weight	0
pattern	0
of	0
urinary	0
proteins	0
can	0
be	0
used	0
to	0
provide	0
diagnostic	0
information	0
about	0
the	0
possible	0
site	0
of	0
renal	3
damage	4
.	0

A	0
catch	0
in	0
the	0
Reye	3
.	0

Twenty	0
-	0
six	0
cases	0
of	0
Reye	3
syndrome	4
from	0
The	0
Children	0
'	0
s	0
Hospital	0
,	0
Camperdown	0
,	0
Australia	0
,	0
occurring	0
between	0
1973	0
and	0
1982	0
were	0
reviewed	0
.	0

0f	0
these	0
,	0
20	0
cases	0
met	0
the	0
US	0
Public	0
Health	0
Service	0
Centers	0
for	0
Disease	0
Control	0
criteria	0
for	0
the	0
diagnosis	0
of	0
Reye	3
syndrome	4
.	0

Aspirin	1
or	0
salicylate	1
ingestion	0
had	0
occurred	0
in	0
only	0
one	0
of	0
the	0
20	0
cases	0
(	0
5	0
%	0
)	0
,	0
and	0
paracetamol	1
(	0
acetaminophen	1
)	0
had	0
been	0
administered	0
in	0
only	0
six	0
of	0
the	0
cases	0
(	0
30	0
%	0
)	0
.	0

Pathologic	0
confirmation	0
of	0
the	0
diagnosis	0
of	0
Reye	3
syndrome	4
was	0
accomplished	0
in	0
90	0
%	0
of	0
the	0
cases	0
.	0

The	0
incidence	0
of	0
Reye	3
syndrome	4
in	0
New	0
South	0
Wales	0
,	0
Australia	0
,	0
is	0
estimated	0
from	0
this	0
study	0
to	0
be	0
approximately	0
nine	0
cases	0
per	0
1	0
million	0
children	0
compared	0
with	0
recent	0
US	0
data	0
of	0
ten	0
to	0
20	0
cases	0
per	0
1	0
million	0
children	0
and	0
three	0
to	0
seven	0
cases	0
per	0
1	0
million	0
children	0
in	0
Great	0
Britain	0
.	0

The	0
mortality	0
for	0
these	0
Reye	3
syndrome	4
cases	0
in	0
Australia	0
was	0
45	0
%	0
as	0
compared	0
with	0
a	0
32	0
%	0
case	0
-	0
fatality	0
rate	0
in	0
the	0
United	0
States	0
.	0

In	0
Australia	0
,	0
the	0
pediatric	0
usage	0
of	0
aspirin	1
has	0
been	0
extremely	0
low	0
for	0
the	0
past	0
25	0
years	0
(	0
less	0
than	0
1	0
%	0
of	0
total	0
dosage	0
units	0
sold	0
)	0
,	0
with	0
paracetamol	1
(	0
acetaminophen	1
)	0
dominating	0
the	0
pediatric	0
analgesic	0
and	0
antipyretic	0
market	0
.	0

Reye	3
syndrome	4
may	0
be	0
disappearing	0
from	0
Australia	0
despite	0
a	0
total	0
lack	0
of	0
association	0
with	0
salicylates	1
or	0
aspirin	1
ingestion	0
,	0
since	0
there	0
were	0
no	0
cases	0
found	0
at	0
The	0
Children	0
'	0
s	0
Hospital	0
in	0
1983	0
,	0
1984	0
,	0
or	0
1985	0
.	0

Postpartum	0
psychosis	3
induced	0
by	0
bromocriptine	1
.	0

Two	0
multigravida	0
patients	0
with	0
no	0
prior	0
psychiatric	3
history	0
were	0
seen	0
with	0
postpartum	0
psychosis	3
,	0
having	0
received	0
bromocriptine	1
for	0
inhibition	3
of	4
lactation	4
.	0

Bromocriptine	1
given	0
in	0
high	0
doses	0
has	0
been	0
associated	0
with	0
psychosis	3
in	0
patients	0
receiving	0
the	0
drug	0
for	0
Parkinson	3
'	4
s	4
disease	4
.	0

These	0
cases	0
demonstrate	0
that	0
bromocriptine	1
may	0
cause	0
psychosis	3
even	0
when	0
given	0
in	0
low	0
doses	0
.	0

Hyperglycemic	3
acidotic	4
coma	4
and	0
death	0
in	0
Kearns	3
-	4
Sayre	4
syndrome	4
.	0

This	0
paper	0
presents	0
the	0
clinical	0
and	0
metabolic	0
findings	0
in	0
two	0
young	0
boys	0
with	0
long	0
-	0
standing	0
Kearns	3
-	4
Sayre	4
syndrome	4
.	0

Following	0
short	0
exposure	0
to	0
oral	0
prednisone	1
,	0
both	0
boys	0
developed	0
lethargy	3
,	0
increasing	0
somnolence	3
,	0
polydipsia	3
,	0
polyphagia	3
,	0
and	0
polyuria	3
.	0

Both	0
presented	0
in	0
the	0
emergency	0
room	0
with	0
profound	0
coma	3
,	0
hypotension	3
,	0
severe	0
hyperglycemia	3
,	0
and	0
acidosis	3
.	0

Nonketotic	0
lactic	3
acidosis	4
was	0
present	0
in	0
one	0
and	0
ketosis	3
without	0
a	0
known	0
serum	0
lactate	1
level	0
was	0
present	0
in	0
the	0
other	0
.	0

Respiratory	3
failure	4
rapidly	0
ensued	0
and	0
both	0
patients	0
expired	0
in	0
spite	0
of	0
efforts	0
at	0
resuscitation	0
.	0

We	0
believe	0
these	0
two	0
cases	0
represent	0
a	0
newly	0
described	0
and	0
catastrophic	0
metabolic	3
-	4
endocrine	4
failure	4
in	0
the	0
Kearns	3
-	4
Sayre	4
syndrome	4
.	0

Experimental	0
cyclosporine	1
nephrotoxicity	3
:	0
risk	0
of	0
concomitant	0
chemotherapy	0
.	0

The	0
role	0
of	0
cyclosporine	1
(	0
CSA	1
)	0
alone	0
or	0
in	0
combination	0
with	0
various	0
chemotherapeutics	0
in	0
the	0
development	0
of	0
renal	3
toxicity	4
was	0
evaluated	0
in	0
rats	0
.	0

Administration	0
of	0
20	0
mg	0
/	0
kg	0
/	0
day	0
CSA	1
for	0
4	0
weeks	0
caused	0
renal	0
functional	0
and	0
structural	0
changes	0
similar	0
to	0
those	0
reported	0
in	0
man	0
.	0

The	0
combined	0
administration	0
of	0
CSA	1
and	0
various	0
chemotherapeutic	0
drugs	0
with	0
a	0
nephrotoxic	3
potential	0
,	0
such	0
as	0
gentamicin	1
(	0
at	0
therapeutic	0
doses	0
)	0
,	0
amphothericin	1
B	2
and	0
ketoconazole	1
,	0
which	0
are	0
frequently	0
used	0
in	0
immunosuppressed	0
patients	0
,	0
did	0
not	0
aggravate	0
the	0
CSA	1
induced	0
toxicity	3
in	0
the	0
rat	0
model	0
.	0

Gentamicin	1
at	0
toxic	0
doses	0
,	0
however	0
,	0
increased	0
CSA	1
nephrotoxicity	3
.	0

Thus	0
,	0
the	0
nephrotoxicity	3
induced	0
by	0
CSA	1
has	0
a	0
different	0
pathogenetic	0
mechanism	0
.	0

Diuretics	0
,	0
potassium	1
and	0
arrhythmias	3
in	0
hypertensive	3
coronary	3
disease	4
.	0

It	0
has	0
been	0
proposed	0
that	0
modest	0
changes	0
in	0
plasma	0
potassium	1
can	0
alter	0
the	0
tendency	0
towards	0
cardiac	3
arrhythmias	4
.	0

If	0
this	0
were	0
so	0
,	0
patients	0
with	0
coronary	3
artery	4
disease	4
might	0
be	0
especially	0
susceptible	0
.	0

Thus	0
,	0
myocardial	0
electrical	0
excitability	0
was	0
measured	0
in	0
patients	0
with	0
mild	0
essential	0
hypertension	3
and	0
known	0
coronary	3
artery	4
disease	4
after	0
8	0
weeks	0
of	0
treatment	0
with	0
a	0
potassium	1
-	0
conserving	0
diuretic	0
(	0
amiloride	1
)	0
and	0
a	0
similar	0
period	0
on	0
a	0
potassium	1
-	0
losing	0
diuretic	0
(	0
chlorthalidone	1
)	0
in	0
a	0
randomised	0
study	0
.	0

Plasma	0
potassium	1
concentrations	0
were	0
on	0
average	0
1	0
mmol	0
/	0
L	0
lower	0
during	0
the	0
chlorthalidone	1
phase	0
compared	0
to	0
amiloride	1
therapy	0
.	0

Blood	0
pressure	0
and	0
volume	0
states	0
as	0
assessed	0
by	0
bodyweight	0
,	0
plasma	0
renin	0
and	0
noradrenaline	1
(	0
norepinephrine	1
)	0
concentrations	0
were	0
similar	0
on	0
the	0
2	0
regimens	0
.	0

Compared	0
to	0
amiloride	1
treatment	0
,	0
the	0
chlorthalidone	1
phase	0
was	0
associated	0
with	0
an	0
increased	0
frequency	0
of	0
ventricular	3
ectopic	4
beats	4
(	0
24	0
-	0
hour	0
Holter	0
monitoring	0
)	0
and	0
a	0
higher	0
Lown	0
grading	0
,	0
increased	0
upslope	0
and	0
duration	0
of	0
the	0
monophasic	0
action	0
potential	0
,	0
prolonged	0
ventricular	0
effective	0
refractory	0
period	0
,	0
and	0
increased	0
electrical	0
instability	0
during	0
programmed	0
ventricular	0
stimulation	0
.	0

The	0
above	0
results	0
indicate	0
that	0
because	0
potassium	1
-	0
losing	0
diuretic	0
therapy	0
can	0
increase	0
myocardial	0
electrical	0
excitability	0
in	0
patients	0
with	0
ischaemic	3
heart	4
disease	4
,	0
even	0
minor	0
falls	0
in	0
plasma	0
potassium	1
concentrations	0
are	0
probably	0
best	0
avoided	0
in	0
such	0
patients	0
.	0

Transketolase	0
abnormality	0
in	0
tolazamide	1
-	0
induced	0
Wernicke	3
'	4
s	4
encephalopathy	4
.	0

We	0
studied	0
a	0
thiamine	1
-	0
dependent	0
enzyme	0
,	0
transketolase	0
,	0
from	0
fibroblasts	0
of	0
a	0
diabetic	3
patient	0
who	0
developed	0
Wernicke	3
'	4
s	4
encephalopathy	4
when	0
treated	0
with	0
tolazamide	1
,	0
in	0
order	0
to	0
delineate	0
if	0
this	0
patient	0
also	0
had	0
transketolase	0
abnormality	0
[	0
high	0
Km	0
for	0
thiamine	1
pyrophosphate	2
(	0
TPP	1
)	0
]	0
,	0
as	0
previously	0
reported	0
in	0
postalcoholic	0
Wernicke	3
-	4
Korsakoff	4
syndrome	4
.	0

In	0
addition	0
to	0
this	0
patient	0
,	0
we	0
also	0
studied	0
this	0
enzyme	0
from	0
three	0
diabetic	3
kindreds	0
without	0
any	0
history	0
of	0
Wernicke	3
'	4
s	4
encephalopathy	4
and	0
from	0
four	0
normal	0
controls	0
.	0

We	0
found	0
that	0
the	0
above	0
-	0
mentioned	0
patient	0
and	0
one	0
of	0
the	0
diabetic	3
kindreds	0
with	0
no	0
history	0
of	0
Wernicke	3
'	4
s	4
encephalopathy	4
had	0
abnormal	0
transketolase	0
as	0
determined	0
by	0
its	0
Km	0
for	0
TPP	1
.	0

These	0
data	0
suggest	0
a	0
similarity	0
between	0
postalcoholic	0
Wernicke	3
-	4
Korsakoff	4
syndrome	4
and	0
the	0
patient	0
with	0
tolazamide	1
-	0
induced	0
Wernicke	3
'	4
s	4
encephalopathy	4
from	0
the	0
standpoint	0
of	0
transketolase	0
abnormality	0
.	0

Bradycardia	3
due	0
to	0
trihexyphenidyl	1
hydrochloride	2
.	0

A	0
chronic	0
schizophrenic	3
patient	0
was	0
treated	0
with	0
an	0
anticholinergic	0
drug	0
,	0
trihexyphenidyl	1
hydrochloride	2
.	0

The	0
patient	0
developed	0
,	0
paradoxically	0
,	0
sinus	0
bradycardia	3
.	0

The	0
reaction	0
was	0
specific	0
to	0
trihexyphenidyl	1
and	0
not	0
to	0
other	0
anticholinergic	0
drugs	0
.	0

This	0
antidyskinetic	0
drug	0
is	0
widely	0
used	0
in	0
clinical	0
psychiatric	3
practice	0
and	0
physicians	0
should	0
be	0
aware	0
of	0
this	0
side	0
effect	0
.	0

Post	0
-	0
operative	0
rigidity	3
after	0
fentanyl	1
administration	0
.	0

A	0
case	0
of	0
thoraco	0
-	0
abdominal	0
rigidity	3
leading	0
to	0
respiratory	3
failure	4
is	0
described	0
in	0
the	0
post	0
-	0
operative	0
period	0
in	0
an	0
elderly	0
patient	0
who	0
received	0
a	0
moderate	0
dose	0
of	0
fentanyl	1
.	0

This	0
was	0
successfully	0
reversed	0
by	0
naloxone	1
.	0

The	0
mechanisms	0
possibly	0
implicated	0
in	0
this	0
accident	0
are	0
discussed	0
.	0

Anti	0
-	0
carcinogenic	3
action	0
of	0
phenobarbital	1
given	0
simultaneously	0
with	0
diethylnitrosamine	1
in	0
the	0
rat	0
.	0

The	0
present	0
work	0
has	0
been	0
planned	0
in	0
order	0
to	0
elucidate	0
the	0
effect	0
of	0
phenobarbital	1
(	0
PB	1
:	0
15	0
mg	0
per	0
rat	0
of	0
ingested	0
dose	0
)	0
on	0
carcinogenesis	3
when	0
it	0
is	0
administered	0
simultaneously	0
with	0
diethylnitrosamine	1
(	0
DEN	1
:	0
10	0
mg	0
/	0
kg	0
/	0
day	0
)	0
.	0

Wistar	0
rats	0
(	0
180	0
g	0
)	0
were	0
treated	0
by	0
DEN	1
alone	0
or	0
by	0
DEN	1
+	0
PB	1
during	0
2	0
,	0
4	0
and	0
6	0
weeks	0
according	0
to	0
our	0
schedule	0
for	0
hepatocarcinogenesis	3
.	0

After	0
the	0
end	0
of	0
the	0
treatment	0
,	0
the	0
number	0
and	0
the	0
size	0
of	0
induced	0
PAS	0
positive	0
preneoplastic	3
foci	4
was	0
significantly	0
reduced	0
when	0
PB	1
was	0
given	0
simultaneously	0
with	0
DEN	1
for	0
4	0
and	0
6	0
weeks	0
.	0

The	0
mitotic	0
inhibition	0
and	0
the	0
production	0
of	0
micronuclei	0
normally	0
observed	0
after	0
partial	0
hepatectomy	0
in	0
DEN	1
treated	0
rats	0
were	0
also	0
significantly	0
decreased	0
in	0
DEN	1
+	0
PB	1
treated	0
rats	0
.	0

When	0
the	0
treatment	0
last	0
only	0
2	0
weeks	0
,	0
the	0
presence	0
of	0
PB	1
did	0
not	0
change	0
significantly	0
the	0
last	0
parameters	0
.	0

In	0
DEN	1
+	0
PB	1
treated	0
rats	0
,	0
the	0
survival	0
was	0
prolonged	0
and	0
the	0
tumor	3
incidence	0
decreased	0
as	0
compared	0
with	0
the	0
results	0
obtained	0
by	0
DEN	1
alone	0
.	0

It	0
is	0
concluded	0
that	0
PB	1
,	0
which	0
promotes	0
carcinogenesis	3
when	0
administered	0
after	0
the	0
DEN	1
treatment	0
,	0
reduces	0
the	0
carcinogen	0
effect	0
when	0
given	0
simultaneously	0
with	0
DEN	1
.	0

This	0
'	0
anti	0
-	0
carcinogen	0
'	0
effect	0
acts	0
on	0
the	0
initiation	0
as	0
well	0
as	0
on	0
the	0
promotion	0
of	0
the	0
precancerous	3
lesions	4
.	0

Biochemical	0
investigations	0
are	0
in	0
progress	0
to	0
obtain	0
more	0
information	0
about	0
this	0
'	0
paradoxical	0
'	0
PB	1
effect	0
.	0

Bilateral	3
optic	4
neuropathy	4
due	0
to	0
combined	0
ethambutol	1
and	0
isoniazid	1
treatment	0
.	0

The	0
case	0
of	0
a	0
40	0
-	0
year	0
-	0
old	0
patient	0
who	0
underwent	0
an	0
unsuccessful	0
cadaver	0
kidney	0
transplantation	0
and	0
was	0
treated	0
with	0
ethambutol	1
and	0
isoniazid	1
is	0
reported	0
.	0

A	0
bilateral	3
retrobulbar	4
neuropathy	4
with	0
an	0
unusual	0
central	0
bitemporal	0
hemianopic	0
scotoma	3
was	0
found	0
.	0

Ethambutol	1
was	0
stopped	0
and	0
only	0
small	0
improvement	0
of	0
the	0
visual	0
acuity	0
followed	0
.	0

Isoniazid	1
was	0
discontinued	0
later	0
,	0
followed	0
by	0
a	0
dramatic	0
improvement	0
in	0
the	0
visual	0
acuity	0
.	0

The	0
hazards	0
of	0
optic	0
nerve	0
toxicity	3
due	0
to	0
ethambutol	1
are	0
known	0
.	0

We	0
emphasize	0
the	0
potential	0
danger	0
in	0
the	0
use	0
of	0
ethambutol	1
and	0
isoniazid	1
.	0

A	0
prospective	0
study	0
of	0
adverse	0
reactions	0
associated	0
with	0
vancomycin	1
therapy	0
.	0

A	0
prospective	0
evaluation	0
of	0
the	0
efficacy	0
and	0
safety	0
of	0
vancomycin	1
was	0
conducted	0
in	0
54	0
consecutive	0
patients	0
over	0
a	0
16	0
-	0
month	0
period	0
.	0

Vancomycin	1
was	0
curative	0
in	0
95	0
%	0
of	0
43	0
patients	0
with	0
proven	0
infection	3
.	0

Drugs	0
were	0
ceased	0
in	0
six	0
patients	0
because	0
of	0
adverse	0
reactions	0
;	0
in	0
three	0
of	0
these	0
vancomycin	1
was	0
considered	0
the	0
likely	0
cause	0
.	0

Reactions	0
included	0
thrombophlebitis	3
(	0
20	0
of	0
54	0
patients	0
)	0
,	0
rash	3
(	0
4	0
of	0
54	0
)	0
,	0
nephrotoxicity	3
(	0
4	0
of	0
50	0
)	0
,	0
proteinuria	3
(	0
1	0
of	0
50	0
)	0
and	0
ototoxicity	3
(	0
1	0
of	0
11	0
patients	0
tested	0
by	0
audiometry	0
)	0
.	0

Thrombophlebitis	3
occurred	0
only	0
with	0
infusion	0
through	0
peripheral	0
cannulae	0
;	0
nephrotoxicity	3
and	0
ototoxicity	3
were	0
confined	0
to	0
patients	0
receiving	0
an	0
aminoglycoside	1
plus	0
vancomycin	1
.	0

We	0
conclude	0
that	0
vancomycin	1
,	0
administered	0
appropriately	0
,	0
constitutes	0
safe	0
,	0
effective	0
therapy	0
for	0
infections	3
caused	0
by	0
susceptible	0
bacteria	0
.	0

Factors	0
associated	0
with	0
nephrotoxicity	3
and	0
clinical	0
outcome	0
in	0
patients	0
receiving	0
amikacin	1
.	0

Data	0
from	0
60	0
patients	0
treated	0
with	0
amikacin	1
were	0
analyzed	0
for	0
factors	0
associated	0
with	0
nephrotoxicity	3
.	0

In	0
42	0
of	0
these	0
patients	0
,	0
data	0
were	0
examined	0
for	0
factors	0
associated	0
with	0
clinical	0
outcome	0
.	0

Variables	0
evaluated	0
included	0
patient	0
weight	0
,	0
age	0
,	0
sex	0
,	0
serum	0
creatinine	1
level	0
,	0
creatinine	1
clearance	0
,	0
duration	0
of	0
therapy	0
,	0
total	0
dose	0
,	0
mean	0
daily	0
dose	0
,	0
organism	0
minimum	0
inhibitory	0
concentration	0
(	0
MIC	0
)	0
,	0
mean	0
peak	0
levels	0
,	0
mean	0
trough	0
levels	0
,	0
mean	0
area	0
under	0
the	0
serum	0
concentration	0
-	0
time	0
curve	0
(	0
AUC	0
)	0
,	0
total	0
AUC	0
,	0
mean	0
AUC	0
greater	0
than	0
MIC	0
,	0
total	0
AUC	0
greater	0
than	0
MIC	0
,	0
mean	0
Schumacher	0
'	0
s	0
intensity	0
factor	0
(	0
IF	0
)	0
,	0
total	0
IF	0
,	0
In	0
(	0
mean	0
maximum	0
concentration	0
[	0
Cmax	0
]	0
/	0
MIC	0
)	0
.	0

Model	0
-	0
dependent	0
pharmacokinetic	0
parameters	0
were	0
calculated	0
by	0
computer	0
based	0
on	0
a	0
one	0
-	0
compartment	0
model	0
.	0

When	0
the	0
parameters	0
were	0
examined	0
individually	0
,	0
duration	0
of	0
therapy	0
and	0
total	0
AUC	0
correlated	0
significantly	0
(	0
P	0
less	0
than	0
.	0
05	0
)	0
with	0
nephrotoxicity	3
.	0

In	0
contrast	0
,	0
a	0
stepwise	0
discriminant	0
function	0
analysis	0
identified	0
only	0
duration	0
of	0
therapy	0
(	0
P	0
less	0
than	0
.	0
001	0
)	0
as	0
an	0
important	0
factor	0
.	0

Based	0
on	0
this	0
model	0
and	0
on	0
Bayes	0
'	0
theorem	0
,	0
the	0
predictive	0
accuracy	0
of	0
identifying	0
"	0
nephrotoxic	3
"	0
patients	0
increased	0
from	0
0	0
.	0
17	0
to	0
0	0
.	0
39	0
.	0

When	0
examined	0
individually	0
,	0
mean	0
IF	0
,	0
MIC	0
,	0
total	0
dose	0
,	0
mean	0
daily	0
dose	0
,	0
and	0
ln	0
(	0
mean	0
Cmax	0
/	0
MIC	0
)	0
correlated	0
significantly	0
(	0
P	0
less	0
than	0
.	0
05	0
)	0
with	0
cure	0
.	0

In	0
contrast	0
,	0
a	0
simultaneous	0
multivariable	0
analysis	0
identified	0
IF	0
,	0
MIC	0
,	0
and	0
total	0
dose	0
according	0
to	0
one	0
model	0
and	0
ln	0
(	0
mean	0
Cmax	0
/	0
MIC	0
)	0
according	0
to	0
a	0
second	0
statistical	0
model	0
of	0
parameters	0
selected	0
to	0
have	0
the	0
greatest	0
prospective	0
value	0
.	0

Based	0
on	0
Bayes	0
'	0
theorem	0
and	0
the	0
first	0
model	0
,	0
the	0
predictive	0
accuracy	0
of	0
identifying	0
patients	0
not	0
cured	0
increased	0
from	0
0	0
.	0
19	0
to	0
0	0
.	0
83	0
.	0

For	0
the	0
second	0
model	0
,	0
the	0
predictive	0
accuracy	0
increased	0
from	0
0	0
.	0
19	0
to	0
0	0
.	0
50	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Cardiac	3
toxicity	4
of	0
5	1
-	2
fluorouracil	2
.	0

Report	0
of	0
a	0
case	0
of	0
spontaneous	0
angina	3
.	0

We	0
report	0
a	0
case	0
of	0
a	0
patient	0
with	0
colon	3
carcinoma	4
and	0
liver	0
metastasis	3
who	0
presented	0
chest	3
pain	4
after	0
5	1
-	2
fluorouracil	2
(	0
5	1
-	2
FU	2
)	0
administration	0
.	0

Clinical	0
electrocardiographic	0
evolution	0
was	0
similar	0
to	0
that	0
observed	0
in	0
Prinzmetal	3
'	4
s	4
angina	4
,	0
and	0
chest	3
pain	4
promptly	0
resolved	0
with	0
nifedipine	1
.	0

These	0
data	0
suggest	0
that	0
coronary	3
spasm	4
may	0
be	0
the	0
cause	0
of	0
cardiotoxicity	3
due	0
to	0
5	1
-	2
FU	2
,	0
and	0
that	0
calcium	1
antagonists	0
may	0
probably	0
be	0
used	0
in	0
the	0
prevention	0
or	0
treatment	0
of	0
5	1
-	2
FU	2
cardiotoxicity	3
.	0

Dose	0
-	0
related	0
beneficial	0
and	0
adverse	0
effects	0
of	0
dietary	0
corticosterone	1
on	0
organophosphorus	1
-	0
induced	0
delayed	0
neuropathy	3
in	0
chickens	0
.	0

Tri	1
-	2
ortho	2
-	2
tolyl	2
phosphate	2
(	0
T0TP	1
)	0
,	0
360	0
mg	0
/	0
kg	0
,	0
po	0
,	0
and	0
0	1
,	2
0	2
'	2
-	2
diisopropyl	2
phosphorofluoridate	2
(	0
DFP	1
)	0
,	0
1	0
mg	0
/	0
kg	0
sc	0
,	0
were	0
administered	0
to	0
adult	0
White	0
Leghorn	0
chickens	0
24	0
hr	0
after	0
they	0
were	0
placed	0
on	0
diets	0
containing	0
0	0
to	0
300	0
ppm	0
corticosterone	1
.	0

Supplemented	0
diets	0
were	0
continued	0
until	0
clinical	0
signs	0
and	0
lesions	0
of	0
delayed	0
neuropathy	3
appeared	0
.	0

Although	0
low	0
concentrations	0
(	0
less	0
than	0
or	0
equal	0
to	0
50	0
ppm	0
)	0
of	0
corticosterone	1
had	0
beneficial	0
effects	0
on	0
T0TP	1
-	0
induced	0
neuropathy	3
,	0
greater	0
than	0
or	0
equal	0
to	0
200	0
ppm	0
exacerbated	0
clinical	0
signs	0
in	0
chickens	0
given	0
either	0
T0TP	1
or	0
DFP	1
.	0

Neurotoxic	3
esterase	0
activities	0
24	0
hr	0
after	0
T0TP	1
or	0
DFP	1
were	0
less	0
than	0
20	0
%	0
of	0
values	0
measured	0
in	0
chickens	0
not	0
given	0
organophosphorous	1
compounds	0
.	0

Chickens	0
given	0
200	0
ppm	0
corticosterone	1
without	0
T0TP	1
or	0
DFP	1
had	0
significantly	0
elevated	0
activity	0
of	0
plasma	0
cholinesterase	0
and	0
significantly	0
inhibited	0
activity	0
of	0
liver	0
carboxylesterase	0
.	0

Degenerating	3
myelinated	4
fibers	4
were	0
also	0
evident	0
in	0
distal	0
levels	0
of	0
the	0
peripheral	0
nerves	0
of	0
chickens	0
given	0
T0TP	1
or	0
DFP	1
.	0

Hepatotoxicity	3
of	0
amiodarone	1
.	0

Amiodarone	1
has	0
proved	0
very	0
effective	0
in	0
the	0
treatment	0
of	0
otherwise	0
resistant	0
cardiac	0
tachyarrhythmias	3
.	0

The	0
use	0
of	0
amiodarone	1
has	0
,	0
however	0
,	0
been	0
limited	0
due	0
to	0
its	0
serious	0
side	0
-	0
effects	0
.	0

A	0
patient	0
with	0
cholestatic	3
hepatitis	4
due	0
to	0
amiodarone	1
treatment	0
is	0
presented	0
below	0
and	0
a	0
review	0
of	0
the	0
hepatotoxicity	3
of	0
amiodarone	1
is	0
given	0
.	0

It	0
is	0
concluded	0
that	0
solid	0
evidence	0
exists	0
of	0
hepatic	3
injury	4
due	0
to	0
amiodarone	1
treatment	0
,	0
including	0
steatosis	3
,	0
alterations	0
resembling	0
alcoholic	3
hepatitis	4
,	0
cholestatic	3
hepatitis	4
and	0
micronodular	0
cirrhosis	3
of	4
the	4
liver	4
.	0

Patients	0
receiving	0
amiodarone	1
should	0
be	0
regularly	0
screened	0
with	0
respect	0
to	0
hepatic	0
enzyme	0
levels	0
.	0

Therapy	0
should	0
be	0
discontinued	0
on	0
the	0
suspicion	0
of	0
cholestatic	3
injury	4
or	0
hepatomegaly	3
.	0

Promotional	0
effects	0
of	0
testosterone	1
and	0
dietary	0
fat	0
on	0
prostate	0
carcinogenesis	3
in	0
genetically	0
susceptible	0
rats	0
.	0

Germfree	0
(	0
GF	0
)	0
Lobund	0
strain	0
Wistar	0
(	0
LW	0
)	0
rats	0
,	0
fed	0
vegetable	0
diet	0
L	0
-	0
485	0
,	0
have	0
developed	0
prostate	3
adenocarcinomas	4
spontaneously	0
(	0
10	0
%	0
incidence	0
)	0
at	0
average	0
age	0
34	0
months	0
.	0

Conventional	0
LW	0
rats	0
,	0
implanted	0
with	0
testosterone	1
at	0
age	0
4	0
months	0
,	0
developed	0
a	0
higher	0
incidence	0
of	0
prostate	3
cancer	4
after	0
an	0
average	0
interval	0
of	0
14	0
months	0
:	0
24	0
%	0
had	0
developed	0
gross	0
tumors	3
,	0
and	0
40	0
%	0
when	0
it	0
included	0
microscopic	0
tumors	3
.	0

Preliminary	0
results	0
indicate	0
that	0
testosterone	1
-	0
treated	0
LW	0
rats	0
that	0
were	0
fed	0
the	0
same	0
diet	0
,	0
which	0
was	0
supplemented	0
with	0
corn	0
oil	0
up	0
to	0
20	0
%	0
fat	0
,	0
developed	0
prostate	3
cancer	4
after	0
intervals	0
of	0
6	0
-	0
12	0
months	0
.	0

Aged	0
GF	0
Sprague	0
-	0
Dawley	0
(	0
SD	0
)	0
rats	0
have	0
not	0
developed	0
prostate	3
cancer	4
spontaneously	0
.	0

Conventional	0
SD	0
rats	0
fed	0
diet	0
L	0
-	0
485	0
and	0
treated	0
with	0
testosterone	1
developed	0
only	0
prostatitis	3
.	0

Experimental	0
designs	0
should	0
consider	0
genetic	0
susceptibility	0
as	0
a	0
basic	0
prerequisite	0
for	0
studies	0
on	0
experimental	0
prostate	3
cancer	4
.	0

Time	0
course	0
alterations	0
of	0
QTC	0
interval	0
due	0
to	0
hypaque	1
76	2
.	0

Sequential	0
measurement	0
of	0
QT	0
interval	0
during	0
left	0
ventricular	0
angiography	0
was	0
made	0
30	0
seconds	0
and	0
one	0
,	0
three	0
,	0
five	0
and	0
ten	0
minutes	0
after	0
injection	0
of	0
hypaque	1
76	2
.	0

The	0
subjects	0
were	0
ten	0
patients	0
found	0
to	0
have	0
normal	0
left	0
ventricles	0
and	0
coronary	0
arteries	0
.	0

Significant	0
QTC	3
prolongation	4
occurred	0
in	0
30	0
seconds	0
to	0
one	0
minute	0
in	0
association	0
with	0
marked	0
hypotension	3
and	0
elevation	0
of	0
cardiac	0
output	0
.	0

Rat	0
extraocular	0
muscle	0
regeneration	0
.	0

Repair	0
of	0
local	0
anesthetic	0
-	0
induced	0
damage	0
.	0

Local	0
anesthetics	0
that	0
are	0
commonly	0
used	0
in	0
ophthalmic	0
surgery	0
(	0
0	0
.	0
75	0
%	0
bupivacaine	1
hydrochloride	2
,	0
2	0
.	0
0	0
%	0
mepivacaine	1
hydrochloride	2
,	0
and	0
2	0
.	0
0	0
%	0
lidocaine	1
hydrochloride	2
plus	0
1	0
:	0
100	0
,	0
000	0
epinephrine	1
)	0
were	0
injected	0
into	0
the	0
retrobulbar	0
area	0
of	0
rat	0
eyes	0
.	0

Controls	0
were	0
injected	0
with	0
physiological	0
saline	0
.	0

All	0
three	0
anesthetics	0
produced	0
massive	0
degeneration	0
of	0
the	0
extraocular	0
muscles	0
.	0

Muscle	3
degeneration	4
is	0
followed	0
by	0
regeneration	0
of	0
the	0
damaged	0
muscle	0
fibers	0
.	0

In	0
addition	0
to	0
muscle	3
damage	4
,	0
severe	0
damage	0
was	0
also	0
seen	0
in	0
harderian	0
glands	0
,	0
especially	0
after	0
exposure	0
to	0
mepivacaine	1
and	0
lidocaine	1
plus	0
epinephrine	1
.	0

With	0
these	0
findings	0
in	0
rats	0
,	0
it	0
is	0
hypothesized	0
that	0
the	0
temporary	0
diplopia	3
sometimes	0
seen	0
in	0
patients	0
after	0
ophthalmic	0
surgery	0
might	0
be	0
due	0
to	0
anesthetic	0
-	0
induced	0
damage	0
to	0
the	0
extraocular	0
muscles	0
.	0

Gentamicin	1
nephropathy	3
in	0
a	0
neonate	0
.	0

The	0
clinical	0
and	0
autopsy	0
findings	0
in	0
a	0
premature	0
baby	0
who	0
died	0
of	0
acute	3
renal	4
failure	4
after	0
therapy	0
with	0
gentamicin	1
(	0
5	0
mg	0
/	0
kg	0
/	0
day	0
)	0
and	0
penicillin	1
are	0
presented	0
.	0

The	0
serum	0
gentamicin	1
concentration	0
had	0
reached	0
toxic	0
levels	0
when	0
anuria	3
developed	0
.	0

Numerous	0
periodic	1
acid	2
Schiff	0
(	0
PAS	0
)	0
positive	0
,	0
diastase	0
resistant	0
cytoplasmic	0
inclusion	0
bodies	0
which	0
appeared	0
as	0
myelin	0
figures	0
in	0
cytosegresomes	0
under	0
the	0
electron	0
microscope	0
were	0
identified	0
in	0
the	0
proximal	0
convoluted	0
tubules	0
.	0

The	0
pathological	0
changes	0
induced	0
by	0
gentamicin	1
in	0
the	0
human	0
neonatal	0
kidneys	0
have	0
not	0
been	0
previously	0
reported	0
.	0

Induction	0
by	0
paracetamol	1
of	0
bladder	3
and	4
liver	4
tumours	4
in	0
the	0
rat	0
.	0

Effects	0
on	0
hepatocyte	0
fine	0
structure	0
.	0

Groups	0
of	0
male	0
and	0
female	0
inbred	0
Leeds	0
strain	0
rats	0
were	0
fed	0
diets	0
containing	0
either	0
0	0
.	0
5	0
%	0
or	0
1	0
.	0
0	0
%	0
paracetamol	1
by	0
weight	0
for	0
up	0
to	0
18	0
months	0
.	0

At	0
the	0
1	0
.	0
0	0
%	0
dosage	0
level	0
,	0
20	0
%	0
of	0
rats	0
of	0
both	0
sexes	0
developed	0
neoplastic	0
nodules	0
of	0
the	0
liver	0
,	0
a	0
statistically	0
significant	0
incidence	0
.	0

These	0
rats	0
also	0
showed	0
gross	0
enlargement	0
of	0
their	0
livers	0
and	0
an	0
increase	0
in	0
foci	0
of	0
cellular	0
alteration	0
,	0
the	0
latter	0
also	0
being	0
observed	0
in	0
the	0
low	0
dosage	0
male	0
rats	0
.	0

Papillomas	3
of	0
the	0
transitional	0
epithelium	0
of	0
the	0
bladder	0
developed	0
in	0
all	0
paracetamol	1
-	0
treated	0
groups	0
,	0
and	0
three	0
rats	0
bore	0
bladder	3
carcinomas	4
.	0

However	0
,	0
significant	0
yields	0
of	0
bladder	3
tumours	4
were	0
only	0
obtained	0
from	0
low	0
dosage	0
females	0
and	0
high	0
dosage	0
males	0
.	0

Additionally	0
,	0
20	0
to	0
25	0
%	0
of	0
paracetamol	1
-	0
treated	0
rats	0
developed	0
hyperplasia	3
of	0
the	0
bladder	0
epithelium	0
,	0
which	0
was	0
not	0
coincident	0
with	0
the	0
presence	0
of	0
bladder	3
calculi	4
.	0

A	0
low	0
yield	0
of	0
tumours	3
at	0
various	0
other	0
sites	0
also	0
arose	0
following	0
paracetamol	1
feeding	0
.	0

An	0
electron	0
microscope	0
study	0
of	0
the	0
livers	0
of	0
paracetamol	1
-	0
treated	0
rats	0
revealed	0
ultrastructural	0
changes	0
in	0
the	0
hepatocytes	0
that	0
resemble	0
those	0
that	0
result	0
from	0
exposure	0
to	0
a	0
variety	0
of	0
known	0
hepatocarcinogens	3
.	0

Transient	0
hemiparesis	3
:	0
a	0
rare	0
manifestation	0
of	0
diphenylhydantoin	1
toxicity	3
.	0

Report	0
of	0
two	0
cases	0
.	0

Among	0
the	0
common	0
side	0
effects	0
of	0
diphenylhydantoin	1
(	0
DPH	1
)	0
overdose	3
,	0
the	0
most	0
frequently	0
encountered	0
neurological	0
signs	0
are	0
those	0
of	0
cerebellar	3
dysfunction	4
.	0

Very	0
rarely	0
,	0
the	0
toxic	0
neurological	0
manifestations	0
of	0
this	0
drug	0
are	0
of	0
cerebral	0
origin	0
.	0

Two	0
patients	0
are	0
presented	0
who	0
suffered	0
progressive	0
hemiparesis	3
due	0
to	0
DPH	1
overdose	3
.	0

Both	0
had	0
brain	0
surgery	0
before	0
DPH	1
treatment	0
.	0

It	0
is	0
assumed	0
that	0
patients	0
with	0
some	0
cerebral	3
damage	4
are	0
liable	0
to	0
manifest	0
DPH	1
toxicity	3
as	0
focal	0
neurological	0
signs	0
.	0

Tiapride	1
in	0
levodopa	1
-	0
induced	0
involuntary	3
movements	4
.	0

Tiapride	1
,	0
a	0
substituted	0
benzamide	1
derivative	0
closely	0
related	0
to	0
metoclopramide	1
,	0
reduced	0
levodopa	1
-	0
induced	0
peak	0
dose	0
involuntary	3
movements	4
in	0
16	0
patients	0
with	0
idiopathic	3
Parkinson	4
'	4
s	4
disease	4
.	0

However	0
,	0
an	0
unacceptable	0
increase	0
in	0
disability	0
from	0
Parkinsonism	3
with	0
aggravation	0
of	0
end	0
-	0
of	0
-	0
dose	0
akinesia	3
led	0
to	0
its	0
cessation	0
in	0
14	0
patients	0
.	0

Tiapride	1
had	0
no	0
effect	0
on	0
levodopa	1
-	0
induced	0
early	0
morning	0
of	0
"	0
off	0
-	0
period	0
"	0
segmental	0
dystonia	3
.	0

These	0
results	0
fail	0
to	0
support	0
the	0
notion	0
that	0
levodopa	1
-	0
induced	0
dyskinesias	3
are	0
caused	0
by	0
overstimulation	0
of	0
a	0
separate	0
group	0
of	0
dopamine	1
receptors	0
.	0

Quinidine	1
hepatitis	3
.	0

Long	0
-	0
term	0
administration	0
of	0
quinidine	1
was	0
associated	0
with	0
persistent	0
elevation	0
of	0
serum	0
concentrations	0
of	0
SG0T	0
,	0
lactic	1
acid	2
dehydrogenase	0
,	0
and	0
alkaline	0
phosphatase	0
.	0

Liver	0
biopsy	0
showed	0
active	0
hepatitis	3
.	0

Discontinuance	0
of	0
quinidine	1
therapy	0
led	0
to	0
normalization	0
of	0
liver	0
function	0
tests	0
.	0

A	0
challenge	0
dose	0
of	0
quinidine	1
caused	0
clinical	0
symptoms	0
and	0
abrupt	0
elevation	0
of	0
SG0T	0
,	0
alkaline	0
phosphatase	0
,	0
and	0
lactic	1
acid	2
dehydrogenase	0
values	0
.	0

We	0
concluded	0
that	0
this	0
patient	0
had	0
quinidine	1
hepatotoxicity	3
and	0
believe	0
that	0
this	0
is	0
the	0
first	0
case	0
reported	0
with	0
liver	0
biopsy	0
documentation	0
.	0

This	0
report	0
also	0
suggests	0
that	0
,	0
even	0
after	0
long	0
-	0
term	0
administration	0
,	0
the	0
hepatic	3
toxicity	4
is	0
reversible	0
.	0

Arterial	0
thromboembolism	3
in	0
patients	0
receiving	0
systemic	0
heparin	1
therapy	0
:	0
a	0
complication	0
associated	0
with	0
heparin	1
-	0
induced	0
thrombocytopenia	3
.	0

Arterial	0
thromboembolism	3
is	0
a	0
recognized	0
complication	0
of	0
systemic	0
heparin	1
therapy	0
.	0

Characteristic	0
of	0
the	0
entity	0
is	0
arterial	3
occlusion	4
by	0
platelet	0
-	0
fibrin	0
thrombi	3
with	0
distal	0
ischemia	3
occurring	0
four	0
to	0
twenty	0
days	0
after	0
the	0
initiation	0
of	0
heparin	1
therapy	0
,	0
preceded	0
by	0
profound	0
thrombocytopenia	3
with	0
platelet	0
counts	0
in	0
the	0
range	0
of	0
30	0
,	0
000	0
to	0
40	0
,	0
000	0
per	0
cubic	0
millimeter	0
.	0

The	0
clinically	0
apparent	0
occlusion	0
may	0
be	0
preceded	0
by	0
gastrointestinal	3
and	4
musculoskeletal	4
symptoms	4
that	0
appear	0
to	0
be	0
ischemic	3
in	0
origin	0
,	0
and	0
might	0
serve	0
to	0
warn	0
the	0
clinician	0
of	0
these	0
complications	0
.	0

Previous	0
reports	0
of	0
these	0
phenomena	0
as	0
well	0
as	0
recent	0
studies	0
of	0
the	0
effect	0
of	0
heparin	1
are	0
reviewed	0
.	0

The	0
common	0
factor	0
relating	0
thromboembolism	3
and	0
thrombocytopenia	3
is	0
heparin	1
-	0
induced	0
platelet	3
aggregation	4
.	0

Appropriate	0
treatment	0
consists	0
of	0
discontinuation	0
of	0
heparin	1
,	0
and	0
anticoagulation	0
with	0
sodium	1
warfarin	2
if	0
necessary	0
.	0

Vascular	0
procedures	0
are	0
performed	0
as	0
indicated	0
.	0

Pharmacology	0
of	0
GYKI	1
-	2
41	2
099	2
(	0
chlorpropanol	1
,	0
Tobanum	1
)	0
a	0
new	0
potent	0
beta	0
-	0
adrenergic	0
antagonist	0
.	0

The	0
compound	0
GYKI	1
-	2
41	2
099	2
,	0
as	0
a	0
beta	0
-	0
adrenergic	0
antagonist	0
,	0
is	0
3	0
-	0
8	0
times	0
more	0
potent	0
than	0
propranolol	1
in	0
vitro	0
and	0
in	0
vivo	0
.	0

Its	0
antiarrhythmic	0
effectiveness	0
surpasses	0
that	0
of	0
propranolol	1
and	0
pindolol	1
inhibiting	0
the	0
ouabain	1
arrhythmia	3
in	0
dogs	0
and	0
cats	0
.	0

GYKI	1
-	2
41	2
900	2
has	0
a	0
negligible	0
cardiodepressant	0
activity	0
;	0
it	0
is	0
not	0
cardioselective	0
.	0

The	0
compound	0
shows	0
a	0
rapid	0
and	0
long	0
lasting	0
effect	0
.	0

There	0
was	0
a	0
prolonged	0
elimination	0
of	0
the	0
radioactivity	0
after	0
the	0
injection	0
of	0
14C	1
-	2
41	2
099	2
to	0
rats	0
and	0
dogs	0
.	0

The	0
half	0
life	0
of	0
the	0
unlabeled	0
substance	0
in	0
humans	0
was	0
more	0
than	0
10	0
hours	0
.	0

Adverse	0
reactions	0
to	0
bendrofluazide	1
and	0
propranolol	1
for	0
the	0
treatment	0
of	0
mild	0
hypertension	3
.	0

Report	0
of	0
Medical	0
Research	0
Council	0
Working	0
Party	0
on	0
Mild	0
to	0
Moderate	0
Hypertension	3
.	0

Participants	0
in	0
the	0
Medical	0
Research	0
Council	0
treatment	0
trial	0
for	0
mild	0
hypertension	3
are	0
randomly	0
allocated	0
to	0
one	0
of	0
four	0
treatment	0
groups	0
:	0
bendrofluazide	1
,	0
propranolol	1
,	0
or	0
a	0
placebo	0
for	0
either	0
of	0
these	0
drugs	0
.	0

The	0
trial	0
is	0
single	0
-	0
blind	0
.	0

23	0
582	0
patient	0
-	0
years	0
of	0
observation	0
have	0
been	0
completed	0
so	0
far	0
,	0
10	0
684	0
on	0
active	0
drugs	0
and	0
12	0
898	0
on	0
placebos	0
.	0

The	0
results	0
show	0
an	0
association	0
between	0
bendrofluazide	1
treatment	0
and	0
impotence	3
,	0
and	0
impotence	3
also	0
occurred	0
more	0
frequently	0
in	0
patients	0
taking	0
propranolol	1
than	0
in	0
those	0
taking	0
placebos	0
.	0

0ther	0
adverse	0
reactions	0
significantly	0
linked	0
with	0
active	0
drugs	0
include	0
impaired	3
glucose	4
tolerance	4
in	0
men	0
and	0
women	0
and	0
gout	3
in	0
men	0
,	0
associated	0
with	0
bendrofluazide	1
treatment	0
,	0
and	0
Raynaud	3
'	4
s	4
phenomenon	4
and	0
dyspnoea	3
in	0
men	0
and	0
women	0
taking	0
propranolol	1
.	0

No	0
corneal	3
disease	4
is	0
known	0
to	0
have	0
occurred	0
in	0
the	0
propranolol	1
group	0
.	0

Mean	0
serum	0
potassium	1
level	0
fell	0
,	0
and	0
urea	1
and	0
uric	1
acid	2
levels	0
rose	0
,	0
in	0
men	0
and	0
women	0
taking	0
bendrofluazide	1
.	0

In	0
the	0
propranolol	1
group	0
,	0
serum	0
potassium	1
and	0
uric	1
acid	2
levels	0
rose	0
in	0
both	0
sexes	0
,	0
but	0
the	0
urea	1
level	0
rose	0
significantly	0
in	0
women	0
only	0
.	0

Serotonergic	0
drugs	0
,	0
benzodiazepines	1
and	0
baclofen	1
block	0
muscimol	1
-	0
induced	0
myoclonic	3
jerks	4
in	0
a	0
strain	0
of	0
mice	0
.	0

In	0
male	0
Swiss	0
mice	0
,	0
muscimol	1
produced	0
myoclonic	3
jerks	4
.	0

A	0
3	0
mg	0
/	0
kg	0
(	0
i	0
.	0
p	0
.	0
)	0
dose	0
induced	0
this	0
response	0
in	0
all	0
of	0
the	0
mice	0
tested	0
and	0
the	0
peak	0
response	0
of	0
73	0
jerks	0
per	0
min	0
was	0
observed	0
between	0
27	0
and	0
45	0
min	0
.	0

Increasing	0
the	0
brain	0
serotonin	1
levels	0
by	0
the	0
administration	0
of	0
5	1
-	2
hydroxytryptophan	2
(	0
80	0
-	0
160	0
mg	0
/	0
kg	0
)	0
in	0
combination	0
with	0
a	0
peripheral	0
decarboxylase	0
inhibitor	0
resulted	0
in	0
an	0
inhibition	0
of	0
the	0
muscimol	1
effect	0
.	0

However	0
,	0
in	0
a	0
similar	0
experiment	0
l	1
-	2
dopa	2
(	0
80	0
-	0
160	0
mg	0
/	0
kg	0
)	0
was	0
without	0
effect	0
.	0

In	0
doses	0
of	0
3	0
-	0
10	0
mg	0
/	0
kg	0
,	0
the	0
serotonin	1
receptor	0
agonist	0
MK	1
-	2
212	2
caused	0
a	0
dose	0
-	0
dependent	0
blockade	0
of	0
the	0
response	0
of	0
muscimol	1
.	0

0f	0
the	0
benzodiazepines	1
,	0
clonazepam	1
(	0
0	0
.	0
1	0
-	0
0	0
.	0
3	0
mg	0
/	0
kg	0
)	0
was	0
found	0
to	0
be	0
several	0
fold	0
more	0
potent	0
than	0
diazepam	1
(	0
0	0
.	0
3	0
-	0
3	0
mg	0
/	0
kg	0
)	0
in	0
blocking	0
the	0
myoclonic	3
jerks	4
.	0

While	0
(	0
-	0
)	0
-	0
baclofen	1
(	0
1	0
-	0
3	0
mg	0
/	0
kg	0
)	0
proved	0
to	0
be	0
an	0
effective	0
antagonist	0
of	0
muscimol	1
,	0
its	0
(	0
+	0
)	0
-	0
isomer	0
(	0
5	0
-	0
20	0
mg	0
/	0
kg	0
)	0
lacked	0
this	0
property	0
.	0

Considering	0
the	0
fact	0
that	0
5	1
-	2
HTP	2
and	0
the	0
benzodiazepines	1
have	0
been	0
found	0
to	0
be	0
beneficial	0
in	0
the	0
management	0
of	0
clinical	0
myoclonus	3
,	0
the	0
muscimol	1
-	0
induced	0
myoclonus	3
seems	0
to	0
be	0
a	0
satisfactory	0
animal	0
model	0
that	0
may	0
prove	0
useful	0
for	0
the	0
development	0
of	0
new	0
drug	0
treatments	0
for	0
this	0
condition	0
.	0

0ur	0
present	0
study	0
indicated	0
the	0
possible	0
value	0
of	0
MK	1
-	2
212	2
and	0
(	0
-	0
)	0
-	0
baclofen	1
in	0
the	0
management	0
of	0
clinical	0
myoclonus	3
.	0

Adverse	0
interaction	0
between	0
beta	1
-	2
adrenergic	2
blocking	2
drugs	2
and	0
verapamil	1
-	0
-	0
report	0
of	0
three	0
cases	0
.	0

Three	0
patients	0
with	0
ischaemic	3
heart	4
disease	4
developed	0
profound	0
cardiac	3
failure	4
,	0
hypotension	3
and	0
bradycardia	3
during	0
combined	0
therapy	0
with	0
verapamil	1
and	0
beta	1
-	2
adrenergic	2
blocking	2
drugs	2
.	0

This	0
clinical	0
picture	0
resolved	0
completely	0
with	0
cessation	0
of	0
the	0
combined	0
therapy	0
.	0

Baseline	0
left	0
ventricular	0
function	0
,	0
assessed	0
by	0
cardiac	0
catheterisation	0
or	0
nuclear	0
angiography	0
,	0
was	0
normal	0
in	0
two	0
patients	0
and	0
only	0
mildly	0
reduced	0
in	0
the	0
other	0
.	0

Simultaneously	0
administration	0
of	0
beta	1
-	2
adrenergic	2
blocking	2
drugs	2
and	0
verapamil	1
may	0
result	0
in	0
profound	0
adverse	0
interactions	0
and	0
should	0
only	0
be	0
administered	0
with	0
great	0
caution	0
.	0

Comparison	0
of	0
the	0
effectiveness	0
of	0
ranitidine	1
and	0
cimetidine	1
in	0
inhibiting	0
acid	0
secretion	0
in	0
patients	0
with	0
gastric	0
hypersecretory	0
states	0
.	0

The	0
H2	0
-	0
histamine	1
receptor	0
antagonists	0
ranitidine	1
and	0
cimetidine	1
were	0
compared	0
for	0
their	0
abilities	0
to	0
control	0
gastric	0
acid	0
hypersecretion	0
on	0
a	0
short	0
-	0
and	0
long	0
-	0
term	0
basis	0
in	0
22	0
patients	0
with	0
gastric	0
acid	0
hypersecretory	0
states	0
.	0

Nineteen	0
patients	0
had	0
Zollinger	3
-	4
Ellison	4
syndrome	4
,	0
one	0
patient	0
had	0
systemic	3
mastocytosis	4
,	0
and	0
two	0
patients	0
had	0
idiopathic	0
hypersecretion	0
.	0

The	0
rates	0
of	0
onset	0
of	0
the	0
action	0
of	0
cimetidine	1
and	0
ranitidine	1
were	0
the	0
same	0
.	0

The	0
actions	0
of	0
both	0
drugs	0
were	0
increased	0
by	0
anticholinergic	0
agents	0
,	0
and	0
there	0
was	0
a	0
close	0
correlation	0
between	0
the	0
daily	0
maintenance	0
dose	0
of	0
each	0
drug	0
needed	0
to	0
control	0
acid	0
secretion	0
.	0

However	0
,	0
ranitidine	1
was	0
threefold	0
more	0
potent	0
than	0
cimetidine	1
both	0
in	0
acute	0
inhibition	0
studies	0
and	0
in	0
the	0
median	0
maintenance	0
dose	0
needed	0
(	0
1	0
.	0
2	0
g	0
per	0
day	0
for	0
ranitidine	1
and	0
3	0
.	0
6	0
g	0
per	0
day	0
for	0
cimetidine	1
)	0
.	0

Sixty	0
percent	0
of	0
the	0
males	0
developed	0
breast	0
changes	0
or	0
impotence	3
while	0
taking	0
cimetidine	1
and	0
in	0
all	0
cases	0
these	0
changes	0
disappeared	0
when	0
cimetidine	1
was	0
replaced	0
by	0
ranitidine	1
.	0

Treatment	0
with	0
high	0
doses	0
of	0
cimetidine	1
(	0
one	0
to	0
60	0
months	0
;	0
median	0
,	0
11	0
months	0
)	0
or	0
ranitidine	1
(	0
two	0
to	0
31	0
months	0
;	0
median	0
,	0
14	0
months	0
)	0
was	0
not	0
associated	0
with	0
hepatic	3
or	4
hematologic	4
toxicity	4
or	0
alterations	0
of	0
serum	0
gastrin	0
concentrations	0
,	0
but	0
ranitidine	1
therapy	0
was	0
associated	0
with	0
a	0
significantly	0
lower	0
serum	0
creatinine	1
level	0
than	0
seen	0
with	0
cimetidine	1
therapy	0
.	0

The	0
results	0
show	0
that	0
both	0
drugs	0
can	0
adequately	0
inhibit	0
acid	0
secretion	0
in	0
patients	0
with	0
gastric	0
hypersecretory	0
states	0
.	0

Both	0
are	0
safe	0
at	0
high	0
doses	0
,	0
but	0
ranitidine	1
is	0
threefold	0
more	0
potent	0
and	0
does	0
not	0
cause	0
the	0
antiandrogen	0
side	0
effects	0
frequently	0
seen	0
with	0
high	0
doses	0
of	0
cimetidine	1
.	0

Epileptogenic	0
properties	0
of	0
enflurane	1
and	0
their	0
clinical	0
interpretation	0
.	0

Three	0
cases	0
of	0
EEG	0
changes	0
induced	0
by	0
single	0
exposure	0
to	0
enflurane	1
anesthesia	0
are	0
reported	0
.	0

In	0
one	0
patient	0
,	0
enflurane	1
administered	0
during	0
a	0
donor	0
nephrectomy	0
resulted	0
in	0
unexpected	0
partial	0
motor	0
seizures	3
.	0

Until	0
the	0
cause	0
of	0
the	0
seizures	3
was	0
correctly	0
identified	0
,	0
the	0
patient	0
was	0
inappropriately	0
treated	0
with	0
anticonvulsants	0
.	0

Two	0
other	0
patients	0
suffered	0
from	0
partial	0
,	0
complex	0
and	0
generalized	0
seizures	3
uncontrolled	0
by	0
medication	0
.	0

Epileptic	3
foci	0
delineated	0
and	0
activated	0
by	0
enflurane	1
were	0
surgically	0
ablated	0
and	0
the	0
patients	0
are	0
now	0
seizure	3
-	0
free	0
.	0

Previous	0
exposures	0
to	0
enflurane	1
have	0
to	0
be	0
disclosed	0
to	0
avoid	0
mistakes	0
in	0
clinical	0
interpretation	0
of	0
the	0
EEG	0
.	0

0n	0
the	0
other	0
hand	0
,	0
enflurane	1
may	0
prove	0
to	0
be	0
a	0
safe	0
fast	0
acting	0
activator	0
of	0
epileptic	3
foci	0
during	0
corticography	0
or	0
depth	0
electrode	0
intraoperative	0
recordings	0
.	0

Development	0
of	0
isoproterenol	1
-	0
induced	0
cardiac	3
hypertrophy	4
.	0

The	0
development	0
of	0
cardiac	3
hypertrophy	4
was	0
studied	0
in	0
adult	0
female	0
Wistar	0
rats	0
following	0
daily	0
subcutaneous	0
injections	0
of	0
isoproterenol	1
(	0
IS0	1
)	0
(	0
0	0
.	0
3	0
mg	0
/	0
kg	0
body	0
weight	0
)	0
.	0

A	0
time	0
course	0
was	0
established	0
for	0
the	0
change	0
in	0
tissue	0
mass	0
,	0
RNA	0
and	0
DNA	0
content	0
,	0
as	0
well	0
as	0
hydroxyproline	1
content	0
.	0

Heart	0
weight	0
increased	0
44	0
%	0
after	0
8	0
days	0
of	0
treatment	0
with	0
a	0
half	0
time	0
of	0
3	0
.	0
4	0
days	0
.	0

Ventricular	0
RNA	0
content	0
was	0
elevated	0
26	0
%	0
after	0
24	0
h	0
of	0
a	0
single	0
injection	0
and	0
reached	0
a	0
maximal	0
level	0
following	0
8	0
days	0
of	0
therapy	0
.	0

The	0
half	0
time	0
for	0
RNA	0
accumulation	0
was	0
2	0
.	0
0	0
days	0
.	0

The	0
total	0
content	0
of	0
hydroxyproline	1
remained	0
stable	0
during	0
the	0
first	0
2	0
days	0
of	0
treatment	0
but	0
increased	0
46	0
%	0
after	0
4	0
days	0
of	0
therapy	0
.	0

Ventricular	0
DNA	0
content	0
was	0
unchanged	0
during	0
the	0
early	0
stage	0
(	0
1	0
-	0
4	0
days	0
)	0
of	0
hypertrophic	3
growth	0
but	0
increased	0
to	0
a	0
new	0
steady	0
-	0
state	0
level	0
19	0
%	0
above	0
the	0
controls	0
after	0
8	0
days	0
of	0
treatment	0
.	0

Intraventricular	0
pressures	0
and	0
coronary	0
flow	0
measures	0
were	0
similar	0
for	0
control	0
and	0
experimental	0
animals	0
following	0
4	0
days	0
of	0
developed	0
hypertrophy	3
.	0

However	0
,	0
dP	0
/	0
dt	0
in	0
the	0
IS0	1
-	0
treated	0
hearts	0
was	0
slightly	0
but	0
significantly	0
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
elevated	0
.	0

These	0
data	0
indicate	0
that	0
the	0
adaptive	0
response	0
to	0
IS0	1
shows	0
an	0
early	0
hypertrophic	3
phase	0
(	0
1	0
-	0
4	0
days	0
)	0
characterized	0
by	0
a	0
substantial	0
increase	0
in	0
RNA	0
content	0
and	0
cardiac	0
mass	0
in	0
the	0
absence	0
of	0
changes	0
in	0
DNA	0
.	0

However	0
,	0
prolonged	0
stimulation	0
(	0
8	0
-	0
12	0
days	0
)	0
appears	0
to	0
represent	0
a	0
complex	0
integration	0
of	0
both	0
cellular	0
hypertrophy	3
and	0
hyperplasia	3
within	0
the	0
heart	0
.	0

Multiple	0
side	0
effects	0
of	0
penicillamine	1
therapy	0
in	0
one	0
patient	0
with	0
rheumatoid	3
arthritis	4
.	0

Skin	3
rashes	4
,	0
proteinuria	3
,	0
systemic	3
lupus	4
erythematosus	4
,	0
polymyositis	3
and	0
myasthenia	3
gravis	4
have	0
all	0
been	0
recorded	0
as	0
complications	0
of	0
penicillamine	1
therapy	0
in	0
patients	0
with	0
rheumatoid	3
arthritis	4
.	0

A	0
patient	0
who	0
had	0
developed	0
all	0
5	0
is	0
now	0
described	0
.	0

The	0
skin	3
lesion	4
resembled	0
elastosis	3
perforans	4
serpiginosa	4
,	0
which	0
has	0
been	0
reported	0
as	0
a	0
rare	0
side	0
effect	0
in	0
patients	0
with	0
Wilson	3
'	4
s	4
disease	4
but	0
not	0
in	0
patients	0
with	0
rheumatoid	3
arthritis	4
treated	0
with	0
penicillamine	1
.	0

0bsolete	0
but	0
dangerous	0
antacid	0
preparations	0
.	0

0ne	0
case	0
of	0
acute	0
hypercalcaemia	3
and	0
two	0
of	0
recurrent	0
nephrolithiasis	3
are	0
reported	0
in	0
patients	0
who	0
had	0
regularly	0
consumed	0
large	0
amounts	0
of	0
calcium	1
carbon	2
-	2
ate	2
-	0
sodium	1
bicarbonate	2
powders	0
for	0
more	0
than	0
20	0
years	0
.	0

The	0
powders	0
had	0
been	0
obtained	0
from	0
pharmacists	0
unknown	0
to	0
the	0
patients	0
'	0
medical	0
practitioners	0
.	0

It	0
is	0
suggested	0
that	0
these	0
preparations	0
were	0
responsible	0
for	0
the	0
patient	0
'	0
s	0
problems	0
,	0
and	0
that	0
such	0
powders	0
should	0
no	0
longer	0
be	0
freely	0
obtainable	0
.	0

Doxorubicin	1
cardiomyopathy	3
in	0
children	0
with	0
left	0
-	0
sided	0
Wilms	3
tumor	4
.	0

Two	0
children	0
with	0
Wilms	3
tumor	4
of	0
the	0
left	0
kidney	0
experienced	0
severe	0
anthracycline	1
cardiomyopathy	3
after	0
irradiation	0
to	0
the	0
tumor	3
bed	0
and	0
conventional	0
dosage	0
of	0
doxorubicin	1
.	0

The	0
cardiomyopathy	3
is	0
attributed	0
1	0
)	0
to	0
the	0
fact	0
that	0
radiation	0
fields	0
for	0
left	0
Wilms	3
tumor	4
include	0
the	0
lower	0
portion	0
of	0
the	0
heart	0
and	0
2	0
)	0
to	0
the	0
interaction	0
of	0
doxorubicin	1
and	0
irradiation	0
on	0
cardiac	0
muscle	0
.	0

It	0
is	0
recommended	0
that	0
doxorubicin	1
dosage	0
be	0
sharply	0
restricted	0
in	0
children	0
with	0
Wilms	3
tumor	4
of	0
the	0
left	0
kidney	0
who	0
receive	0
postoperative	0
irradiation	0
.	0

Effects	0
of	0
calcitonin	0
on	0
rat	0
extrapyramidal	0
motor	0
system	0
:	0
behavioral	0
and	0
biochemical	0
data	0
.	0

The	0
effects	0
of	0
i	0
.	0
v	0
.	0
c	0
.	0
injection	0
of	0
human	0
and	0
salmon	0
calcitonin	0
on	0
biochemical	0
and	0
behavioral	0
parameters	0
related	0
to	0
the	0
extrapyramidal	0
motor	0
system	0
,	0
were	0
investigated	0
in	0
male	0
rats	0
.	0

Calcitonin	0
injection	0
resulted	0
in	0
a	0
potentiation	0
of	0
haloperidol	1
-	0
induced	0
catalepsy	3
and	0
a	0
partial	0
prevention	0
of	0
apomorphine	1
-	0
induced	0
hyperactivity	3
.	0

Moreover	0
calcitonin	0
induced	0
a	0
significant	0
decrease	0
in	0
nigral	0
GAD	0
activity	0
but	0
no	0
change	0
in	0
striatal	0
DA	1
and	0
D0PAC	1
concentration	0
or	0
GAD	0
activity	0
.	0

The	0
results	0
are	0
discussed	0
in	0
view	0
of	0
a	0
primary	0
action	0
of	0
calcitonin	0
on	0
the	0
striatonigral	0
GABAergic	0
pathway	0
mediating	0
the	0
DA	1
-	0
related	0
behavioral	0
messages	0
of	0
striatal	0
origin	0
.	0

Naloxazone	1
pretreatment	0
modifies	0
cardiorespiratory	0
,	0
temperature	0
,	0
and	0
behavioral	0
effects	0
of	0
morphine	1
.	0

Behavioral	0
and	0
cardiorespiratory	0
responses	0
to	0
a	0
lethal	0
dose	0
of	0
morphine	1
were	0
evaluated	0
in	0
rats	0
pretreated	0
with	0
saline	0
or	0
naloxazone	1
,	0
an	0
antagonist	0
of	0
high	0
-	0
affinity	0
mu	0
1	0
opioid	0
receptors	0
.	0

Pretreatment	0
with	0
naloxazone	1
significantly	0
blocked	0
morphine	1
analgesia	3
,	0
catalepsy	3
and	0
hypothermia	3
at	0
a	0
dose	0
which	0
completely	0
eliminated	0
high	0
-	0
affinity	0
binding	0
in	0
brain	0
membranes	0
.	0

Moreover	0
,	0
naloxazone	1
significantly	0
attenuated	0
the	0
morphine	1
-	0
induced	0
hypotension	3
and	0
respiratory	3
depression	4
,	0
whereas	0
morphine	1
-	0
induced	0
bradycardia	3
was	0
less	0
affected	0
.	0

Results	0
indicate	0
that	0
subpopulations	0
of	0
mu	0
receptors	0
may	0
mediate	0
selective	0
behavioral	0
and	0
cardiorespiratory	0
responses	0
to	0
morphine	1
.	0

Modification	0
of	0
drug	0
action	0
by	0
hyperammonemia	3
.	0

Pretreatment	0
with	0
ammonium	1
acetate	2
(	0
NH4Ac	1
)	0
(	0
6	0
mmol	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
approximately	0
doubled	0
the	0
time	0
morphine	1
-	0
treated	0
mice	0
remained	0
on	0
a	0
hot	0
surface	0
and	0
similarly	0
increased	0
muscular	0
incoordination	3
by	0
diazepam	1
,	0
but	0
NH4Ac	1
treatment	0
alone	0
had	0
no	0
effect	0
.	0

Thus	0
,	0
hyperammonemia	3
is	0
capable	0
of	0
altering	0
drug	0
action	0
and	0
must	0
be	0
considered	0
along	0
with	0
impaired	0
drug	0
metabolism	0
in	0
enhanced	0
drug	0
responses	0
associated	0
with	0
liver	3
disease	4
.	0

Experiments	0
in	0
vitro	0
showed	0
that	0
acetylcholine	1
-	0
induced	0
catecholamine	1
release	0
from	0
bovine	0
adrenal	0
medulla	0
is	0
depressed	0
as	0
much	0
as	0
50	0
%	0
by	0
0	0
.	0
3	0
mM	0
NH4Ac	1
and	0
KCl	1
-	0
induced	0
contractions	0
of	0
guinea	0
-	0
pig	0
ileum	0
were	0
inhibited	0
20	0
%	0
by	0
5	0
mM	0
NH4Ac	1
.	0

Addition	0
of	0
excess	0
calcium	1
reversed	0
the	0
depression	3
in	0
both	0
tissues	0
,	0
but	0
calcium	1
-	0
independent	0
catecholamine	1
release	0
by	0
acetaldehyde	1
was	0
not	0
blocked	0
by	0
NH4Ac	1
.	0

These	0
results	0
suggested	0
that	0
ammonia	1
blocks	0
calcium	1
channels	0
.	0

Parallels	0
in	0
the	0
actions	0
of	0
NH4Ac	1
and	0
the	0
calcium	1
channel	0
blocker	0
verapamil	1
support	0
this	0
concept	0
.	0

Both	0
verapamil	1
(	0
10	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
and	0
NH4Ac	1
pretreatment	0
enhanced	0
morphine	1
analgesia	3
-	0
and	0
diazepam	1
-	0
induced	0
muscular	0
incoordination	3
and	0
antagonized	0
amphetamine	1
-	0
induced	0
motor	0
activity	0
,	0
and	0
neither	0
verapamil	1
nor	0
NH4Ac	1
affected	0
the	0
convulsant	0
action	0
of	0
metrazol	1
.	0

The	0
data	0
suggest	0
that	0
hyperammonemia	3
exerts	0
a	0
calcium	1
channel	0
blocking	0
action	0
which	0
enhances	0
the	0
effects	0
of	0
central	0
nervous	0
system	0
depressants	0
and	0
certain	0
opioid	0
analgesics	0
.	0

Levodopa	1
-	0
induced	0
dyskinesia	3
and	0
thalamotomy	0
.	0

Levodopa	1
-	0
induced	0
dyskinesia	3
of	0
the	0
limbs	0
in	0
thirteen	0
cases	0
of	0
Parkinsonism	3
,	0
which	0
was	0
choreic	0
,	0
ballistic	0
or	0
dystonic	3
in	0
type	0
,	0
was	0
alleviated	0
almost	0
completely	0
by	0
stereotaxic	0
surgery	0
using	0
a	0
microelectrode	0
technique	0
for	0
the	0
ventralis	0
oralis	0
anterior	0
and	0
posterior	0
nuclei	0
of	0
the	0
thalamus	0
,	0
but	0
much	0
less	0
by	0
the	0
ventralis	0
intermedius	0
nucleus	0
.	0

Control	0
of	0
levodopa	1
-	0
induced	0
dyskinesias	3
by	0
thalamic	3
lesions	4
in	0
the	0
course	0
of	0
routine	0
treatment	0
of	0
Parkinsonism	3
is	0
discussed	0
.	0

Treatment	0
of	0
ifosfamide	1
-	0
induced	0
urothelial	3
toxicity	4
by	0
oral	0
administration	0
of	0
sodium	1
2	2
-	2
mercaptoethane	2
sulphonate	2
(	0
MESNA	1
)	0
to	0
patients	0
with	0
inoperable	0
lung	3
cancer	4
.	0

The	0
protective	0
effect	0
of	0
oral	0
administration	0
of	0
the	0
thiol	1
compound	0
sodium	1
2	2
-	2
mercaptoethane	2
sulphonate	2
(	0
MESNA	1
)	0
against	0
urothelial	3
toxicity	4
induced	0
by	0
ifosfamide	1
(	0
IF	1
)	0
was	0
tested	0
in	0
a	0
group	0
of	0
45	0
patients	0
with	0
inoperable	0
lung	3
cancer	4
under	0
treatment	0
with	0
IF	1
(	0
2250	0
mg	0
/	0
m2	0
on	0
days	0
2	0
-	0
5	0
)	0
as	0
part	0
of	0
a	0
polychemotherapy	0
regimen	0
repeated	0
in	0
a	0
4	0
-	0
week	0
cycle	0
.	0

MESNA	1
was	0
given	0
orally	0
on	0
the	0
days	0
of	0
treatment	0
with	0
IF	1
in	0
3	0
doses	0
of	0
840	0
mg	0
/	0
m2	0
,	0
each	0
administered	0
at	0
0	0
hr	0
(	0
=	0
injection	0
of	0
IF	1
)	0
,	0
4	0
hr	0
and	0
8	0
hr	0
p	0
.	0
i	0
.	0

0ut	0
of	0
a	0
total	0
of	0
88	0
courses	0
of	0
this	0
treatment	0
we	0
observed	0
10	0
episodes	0
of	0
asymptomatic	0
microscopic	0
haematuria	3
and	0
no	0
episodes	0
of	0
gross	0
haematuria	3
.	0

In	0
this	0
group	0
of	0
45	0
patients	0
under	0
protection	0
with	0
MESNA	1
there	0
were	0
5	0
complete	0
remissions	0
and	0
9	0
partial	0
remissions	0
(	0
total	0
31	0
%	0
)	0
.	0

A	0
further	0
group	0
of	0
25	0
patients	0
under	0
polychemotherapy	0
with	0
IF	1
were	0
treated	0
by	0
conventional	0
prophylactic	0
measures	0
(	0
raised	0
fluid	0
intake	0
and	0
forced	0
diuresis	0
)	0
.	0

In	0
this	0
group	0
there	0
were	0
1	0
complete	0
and	0
5	0
partial	0
remissions	0
(	0
total	0
24	0
%	0
)	0
,	0
but	0
nearly	0
all	0
patients	0
developed	0
either	0
gross	0
haematuria	3
and	0
/	0
or	0
symptoms	0
of	0
bladder	3
irritation	4
(	0
cystitis	3
and	0
pollakisuria	3
)	0
.	0

There	0
were	0
no	0
appreciable	0
differences	0
between	0
the	0
MESNA	1
series	0
and	0
the	0
conventional	0
prophylaxis	0
series	0
with	0
respect	0
to	0
either	0
haematological	0
or	0
systemic	0
toxicity	3
of	0
the	0
cytostatic	0
treatment	0
.	0

0ur	0
results	0
support	0
the	0
view	0
that	0
MESNA	1
,	0
given	0
orally	0
in	0
conjunction	0
with	0
combined	0
cytostatic	0
regimens	0
which	0
include	0
IF	1
,	0
simplifies	0
the	0
treatment	0
and	0
provides	0
optimum	0
protection	0
for	0
the	0
urinary	0
epithelium	0
.	0

Protection	0
with	0
oral	0
MESNA	1
is	0
particularly	0
suitable	0
for	0
outpatients	0
.	0

Myoclonic	3
,	4
atonic	4
,	4
and	4
absence	4
seizures	4
following	0
institution	0
of	0
carbamazepine	1
therapy	0
in	0
children	0
.	0

Five	0
children	0
,	0
aged	0
3	0
to	0
11	0
years	0
,	0
treated	0
with	0
carbamazepine	1
for	0
epilepsy	3
,	0
had	0
an	0
acute	0
aberrant	0
reaction	0
characterized	0
by	0
the	0
onset	0
of	0
myoclonic	3
,	4
atypical	4
absence	4
and	4
/	4
or	4
atonic	4
(	4
minor	4
motor	4
)	4
seizures	4
within	0
a	0
few	0
days	0
.	0

When	0
the	0
carbamazepine	1
was	0
discontinued	0
,	0
two	0
of	0
the	0
children	0
returned	0
to	0
their	0
former	0
state	0
very	0
quickly	0
,	0
two	0
had	0
the	0
minor	0
motor	0
seizures	3
resolve	0
in	0
3	0
and	0
6	0
months	0
,	0
and	0
one	0
had	0
the	0
seizures	3
persist	0
.	0

The	0
child	0
in	0
whom	0
the	0
seizures	3
persisted	0
was	0
later	0
found	0
to	0
have	0
ceroid	3
lipofuscinosis	4
.	0

The	0
other	0
children	0
are	0
doing	0
well	0
on	0
other	0
anticonvulsants	0
.	0

Effect	0
of	0
prostaglandin	1
synthetase	0
inhibitors	0
on	0
experimentally	0
induced	0
convulsions	3
in	0
rats	0
.	0

To	0
investigate	0
the	0
relationship	0
of	0
prostaglandins	1
(	0
PGs	1
)	0
to	0
seizure	3
induction	0
,	0
the	0
effects	0
of	0
six	0
PG	0
synthetase	0
inhibitors	0
on	0
convulsions	3
induced	0
by	0
flurothyl	1
,	0
picrotoxin	1
,	0
pentetrazol	1
(	0
PTZ	1
)	0
,	0
electroshock	0
or	0
bicuculline	1
were	0
evaluated	0
.	0

Ibuprofen	1
,	0
sulindac	1
,	0
mefenamic	1
acid	2
,	0
and	0
low	0
dose	0
meclofenamic	1
acid	2
increased	0
the	0
latency	0
-	0
to	0
-	0
onset	0
in	0
the	0
flurothyl	1
and	0
/	0
or	0
PTZ	1
models	0
;	0
the	0
electroshock	0
,	0
picrotoxin	1
and	0
bicuculline	1
models	0
were	0
not	0
significantly	0
affected	0
by	0
any	0
of	0
the	0
pretreatment	0
agents	0
.	0

These	0
results	0
suggest	0
that	0
PGs	1
are	0
involved	0
in	0
the	0
mechanism	0
(	0
s	0
)	0
underlying	0
fluorthyl	1
-	0
and	0
PTZ	1
-	0
induced	0
convulsions	3
,	0
but	0
not	0
picrotoxin	1
-	0
,	0
electroshock	0
-	0
,	0
or	0
bicuculline	1
-	0
induced	0
convulsions	3
.	0

Acute	0
changes	0
of	0
blood	0
ammonia	1
may	0
predict	0
short	0
-	0
term	0
adverse	0
effects	0
of	0
valproic	1
acid	2
.	0

Valproic	1
acid	2
(	0
VPA	1
)	0
was	0
given	0
to	0
24	0
epileptic	3
patients	0
who	0
were	0
already	0
being	0
treated	0
with	0
other	0
antiepileptic	0
drugs	0
.	0

A	0
standardized	0
loading	0
dose	0
of	0
VPA	1
was	0
administered	0
,	0
and	0
venous	0
blood	0
was	0
sampled	0
at	0
0	0
,	0
1	0
,	0
2	0
,	0
3	0
,	0
and	0
4	0
hours	0
.	0

Ammonia	1
(	0
NH3	1
)	0
was	0
higher	0
in	0
patients	0
who	0
,	0
during	0
continuous	0
therapy	0
,	0
complained	0
of	0
drowsiness	3
(	0
7	0
patients	0
)	0
than	0
in	0
those	0
who	0
were	0
symptom	0
-	0
free	0
(	0
17	0
patients	0
)	0
,	0
although	0
VPA	1
plasma	0
levels	0
were	0
similar	0
in	0
both	0
groups	0
.	0

By	0
measuring	0
VPA	1
-	0
induced	0
changes	0
of	0
blood	0
NH3	1
content	0
,	0
it	0
may	0
be	0
possible	0
to	0
identify	0
patients	0
at	0
higher	0
risk	0
of	0
obtundation	0
when	0
VPA	1
is	0
given	0
chronically	0
.	0

Effect	0
of	0
captopril	1
on	0
pre	0
-	0
existing	0
and	0
aminonucleoside	1
-	0
induced	0
proteinuria	3
in	0
spontaneously	0
hypertensive	3
rats	0
.	0

Proteinuria	3
is	0
a	0
side	0
effect	0
of	0
captopril	1
treatment	0
in	0
hypertensive	3
patients	0
.	0

The	0
possibility	0
of	0
reproducing	0
the	0
same	0
renal	3
abnormality	4
with	0
captopril	1
was	0
examined	0
in	0
SHR	0
.	0

0ral	0
administration	0
of	0
captopril	1
at	0
100	0
mg	0
/	0
kg	0
for	0
14	0
days	0
failed	0
to	0
aggravate	0
proteinuria	3
pre	0
-	0
existing	0
in	0
SHR	0
.	0

Also	0
,	0
captopril	1
treatment	0
failed	0
to	0
potentiate	0
or	0
facilitate	0
development	0
of	0
massive	0
proteinuria	3
invoked	0
by	0
puromycin	1
aminonucleoside	2
in	0
SHR	0
.	0

Captopril	1
had	0
little	0
or	0
no	0
demonstrable	0
effects	0
on	0
serum	0
electrolyte	0
concentrations	0
,	0
excretion	0
of	0
urine	0
,	0
sodium	1
and	0
potassium	1
,	0
endogenous	0
creatinine	1
clearance	0
,	0
body	0
weight	0
,	0
and	0
food	0
and	0
water	0
consumption	0
.	0

However	0
,	0
ketone	1
bodies	0
were	0
consistently	0
present	0
in	0
urine	0
and	0
several	0
lethalities	0
occurred	0
during	0
multiple	0
dosing	0
of	0
captopril	1
in	0
SHR	0
.	0

Complete	0
heart	3
block	4
following	0
a	0
single	0
dose	0
of	0
trazodone	1
.	0

Forty	0
minutes	0
after	0
receiving	0
a	0
single	0
starting	0
dose	0
of	0
trazodone	1
,	0
a	0
patient	0
developed	0
complete	0
heart	3
block	4
.	0

The	0
case	0
illustrates	0
that	0
,	0
despite	0
the	0
results	0
of	0
earlier	0
studies	0
,	0
trazodone	1
'	0
s	0
effect	0
on	0
cardiac	0
conduction	0
may	0
be	0
severe	0
in	0
individuals	0
at	0
risk	0
for	0
conduction	0
delay	0
.	0

Phenobarbital	1
-	0
induced	0
dyskinesia	3
in	0
a	0
neurologically	3
-	4
impaired	4
child	0
.	0

A	0
2	0
-	0
year	0
-	0
old	0
child	0
with	0
known	0
neurologic	3
impairment	4
developed	0
a	0
dyskinesia	3
soon	0
after	0
starting	0
phenobarbital	1
therapy	0
for	0
seizures	3
.	0

Known	0
causes	0
of	0
movement	3
disorders	4
were	0
eliminated	0
after	0
evaluation	0
.	0

0n	0
repeat	0
challenge	0
with	0
phenobarbital	1
,	0
the	0
dyskinesia	3
recurred	0
.	0

Phenobarbital	1
should	0
be	0
added	0
to	0
the	0
list	0
of	0
anticonvulsant	0
drugs	0
that	0
can	0
cause	0
movement	3
disorders	4
.	0

Effects	0
of	0
amine	1
pretreatment	0
on	0
ketamine	1
catatonia	3
in	0
pinealectomized	0
or	0
hypophysectomized	0
animals	0
.	0

The	0
present	0
studies	0
were	0
designed	0
to	0
clarify	0
the	0
role	0
of	0
catecholamines	1
and	0
pineal	0
idolamines	0
on	0
ketamine	1
-	0
induced	0
catatonia	3
in	0
the	0
intact	0
,	0
pinealectomized	0
or	0
hypophysectomized	0
chick	0
and	0
rat	0
.	0

In	0
the	0
pinealectomized	0
chick	0
,	0
pretreatment	0
with	0
dopamine	1
increased	0
the	0
duration	0
of	0
catatonia	3
(	0
D0C	0
)	0
after	0
ketamine	1
,	0
but	0
pretreatment	0
with	0
norepinephrine	1
did	0
not	0
.	0

The	0
pineal	0
indolamines	0
exhibited	0
mixed	0
actions	0
.	0

Serotonin	1
and	0
N	1
-	2
acetyl	2
serotonin	2
which	0
augmented	0
ketamine	1
D0C	0
,	0
did	0
not	0
do	0
so	0
in	0
the	0
absence	0
of	0
the	0
pineal	0
gland	0
,	0
whereas	0
melatonin	1
potentiated	0
the	0
ketamine	1
D0C	0
in	0
both	0
the	0
intact	0
and	0
pinealectomized	0
chick	0
.	0

Ketamine	1
was	0
more	0
potent	0
in	0
the	0
hypophysectomized	0
chick	0
and	0
the	0
circadian	0
rhythm	0
noted	0
in	0
the	0
intact	0
chick	0
was	0
absent	0
;	0
furthermore	0
,	0
melatonin	1
did	0
not	0
augment	0
the	0
ketamine	1
D0C	0
whereas	0
dopamine	1
continued	0
to	0
do	0
so	0
.	0

This	0
study	0
did	0
not	0
demonstrate	0
a	0
species	0
difference	0
regarding	0
the	0
role	0
of	0
the	0
amines	1
on	0
the	0
pineal	0
in	0
spite	0
of	0
the	0
immature	0
blood	0
-	0
brain	0
barrier	0
in	0
the	0
young	0
chick	0
and	0
the	0
intact	0
barrier	0
in	0
the	0
rat	0
.	0

In	0
addition	0
,	0
these	0
data	0
indicate	0
a	0
direct	0
role	0
of	0
the	0
pituitary	0
in	0
the	0
augmentation	0
of	0
ketamine	1
D0C	0
induced	0
by	0
melatonin	1
.	0

Furthermore	0
,	0
dopamine	1
appeared	0
to	0
act	0
on	0
systems	0
more	0
closely	0
involved	0
with	0
the	0
induction	0
of	0
ketamine	1
catatonia	3
rather	0
than	0
directly	0
on	0
the	0
pituitary	0
.	0

Heparin	1
-	0
induced	0
thrombocytopenia	3
,	0
thrombosis	3
,	0
and	0
hemorrhage	3
.	0

Sixty	0
-	0
two	0
patients	0
with	0
a	0
heparin	1
-	0
induced	0
thrombocytopenia	3
are	0
reported	0
.	0

Clinical	0
manifestations	0
of	0
this	0
disorder	0
include	0
hemorrhage	3
or	0
,	0
more	0
frequently	0
,	0
thromboembolic	3
events	0
in	0
patients	0
receiving	0
heparin	1
.	0

Laboratory	0
testing	0
has	0
revealed	0
a	3
falling	4
platelet	4
count	4
,	0
increased	0
resistance	0
to	0
heparin	1
,	0
and	0
aggregation	0
of	0
platelets	0
by	0
the	0
patient	0
'	0
s	0
plasma	0
when	0
heparin	1
is	0
added	0
.	0

Immunologic	0
testing	0
has	0
demonstrated	0
the	0
presence	0
of	0
a	0
heparin	1
-	0
dependent	0
platelet	0
membrane	0
antibody	0
.	0

The	0
20	0
deaths	0
,	0
52	0
hemorrhagic	3
and	4
thromboembolic	4
complications	4
,	0
and	0
21	0
surgical	0
procedures	0
to	0
manage	0
the	0
complications	0
confirm	0
the	0
seriousness	0
of	0
the	0
disorder	0
.	0

Specific	0
risk	0
factors	0
have	0
not	0
been	0
identified	0
;	0
therefore	0
,	0
all	0
patients	0
receiving	0
heparin	1
should	0
be	0
monitored	0
.	0

If	0
the	0
platelet	0
count	0
falls	0
to	0
less	0
than	0
100	0
,	0
000	0
/	0
mm3	0
,	0
while	0
the	0
patient	0
is	0
receiving	0
heparin	1
,	0
platelet	3
aggregation	4
testing	0
,	0
using	0
the	0
patient	0
'	0
s	0
plasma	0
,	0
is	0
indicated	0
.	0

Management	0
consists	0
of	0
cessation	0
of	0
heparin	1
,	0
platelet	0
anti	0
-	0
aggregating	0
agents	0
,	0
and	0
alternate	0
forms	0
of	0
anticoagulation	0
when	0
indicated	0
.	0

Ventricular	3
fibrillation	4
from	0
diatrizoate	1
with	0
and	0
without	0
chelating	0
agents	0
.	0

The	0
toxicity	3
of	0
Renografin	1
76	2
%	2
was	0
compared	0
with	0
that	0
of	0
Hypaque	1
76	2
%	2
by	0
selective	0
injection	0
of	0
each	0
into	0
the	0
right	0
coronary	0
artery	0
of	0
dogs	0
.	0

Renografin	1
contains	0
the	0
chelating	0
agents	0
sodium	1
citrate	2
and	0
disodium	1
edetate	2
,	0
while	0
Hypaque	1
contains	0
calcium	1
disodium	2
edetate	2
and	0
no	0
sodium	1
citrate	2
.	0

Ventricular	3
fibrillation	4
occurred	0
significantly	0
more	0
often	0
with	0
Renografin	1
,	0
suggesting	0
that	0
chelating	0
agents	0
contribute	0
to	0
toxicity	3
in	0
coronary	0
angiography	0
.	0

Long	0
-	0
term	0
efficacy	0
and	0
toxicity	3
of	0
high	0
-	0
dose	0
amiodarone	1
therapy	0
for	0
ventricular	3
tachycardia	4
or	0
ventricular	3
fibrillation	4
.	0

Amiodarone	1
was	0
administered	0
to	0
154	0
patients	0
who	0
had	0
sustained	0
,	0
symptomatic	0
ventricular	3
tachycardia	4
(	0
VT	3
)	0
(	0
n	0
=	0
118	0
)	0
or	0
a	0
cardiac	3
arrest	4
(	0
n	0
=	0
36	0
)	0
and	0
who	0
were	0
refractory	0
to	0
conventional	0
antiarrhythmic	0
drugs	0
.	0

The	0
loading	0
dose	0
was	0
800	0
mg	0
/	0
day	0
for	0
6	0
weeks	0
and	0
the	0
maintenance	0
dose	0
was	0
600	0
mg	0
/	0
day	0
.	0

Sixty	0
-	0
nine	0
percent	0
of	0
patients	0
continued	0
treatment	0
with	0
amiodarone	1
and	0
had	0
no	0
recurrence	0
of	0
symptomatic	0
VT	3
or	0
ventricular	3
fibrillation	4
(	0
VF	3
)	0
over	0
a	0
follow	0
-	0
up	0
of	0
6	0
to	0
52	0
months	0
(	0
mean	0
+	0
/	0
-	0
standard	0
deviation	0
14	0
.	0
2	0
+	0
/	0
-	0
8	0
.	0
2	0
)	0
.	0

Six	0
percent	0
of	0
the	0
patients	0
had	0
a	0
nonfatal	0
recurrence	0
of	0
VT	3
and	0
were	0
successfully	0
managed	0
by	0
continuing	0
amiodarone	1
at	0
a	0
higher	0
dose	0
or	0
by	0
the	0
addition	0
of	0
a	0
conventional	0
antiarrhythmic	0
drug	0
.	0

0ne	0
or	0
more	0
adverse	0
drug	0
reactions	0
occurred	0
in	0
51	0
%	0
of	0
patients	0
.	0

Adverse	0
effects	0
forced	0
a	0
reduction	0
in	0
the	0
dose	0
of	0
amiodarone	1
in	0
41	0
%	0
and	0
discontinuation	0
of	0
amiodarone	1
in	0
10	0
%	0
of	0
patients	0
.	0

The	0
most	0
common	0
symptomatic	0
adverse	0
reactions	0
were	0
tremor	3
or	0
ataxia	3
(	0
35	0
%	0
)	0
,	0
nausea	3
and	0
anorexia	3
(	0
8	0
%	0
)	0
,	0
visual	3
halos	4
or	4
blurring	4
(	0
6	0
%	0
)	0
,	0
thyroid	3
function	4
abnormalities	4
(	0
6	0
%	0
)	0
and	0
pulmonary	3
interstitial	4
infiltrates	4
(	0
5	0
%	0
)	0
.	0

Although	0
large	0
-	0
dose	0
amiodarone	1
is	0
highly	0
effective	0
in	0
the	0
long	0
-	0
term	0
treatment	0
of	0
VT	3
or	0
VF	3
refractory	0
to	0
conventional	0
antiarrhythmic	0
drugs	0
,	0
it	0
causes	0
significant	0
toxicity	3
in	0
approximately	0
50	0
%	0
of	0
patients	0
.	0

However	0
,	0
when	0
the	0
dose	0
is	0
adjusted	0
based	0
on	0
clinical	0
response	0
or	0
the	0
development	0
of	0
adverse	0
effects	0
,	0
75	0
%	0
of	0
patients	0
with	0
VT	3
or	0
VF	3
can	0
be	0
successfully	0
managed	0
with	0
amiodarone	1
.	0

Why	0
may	0
epsilon	1
-	2
aminocaproic	2
acid	2
(	0
EACA	1
)	0
induce	0
myopathy	3
in	0
man	0
?	0

Report	0
of	0
a	0
case	0
and	0
literature	0
review	0
.	0

A	0
case	0
of	0
necrotizing	3
myopathy	4
due	0
to	0
a	0
short	0
epsilon	1
-	2
aminocaproic	2
acid	2
(	0
EACA	1
)	0
treatment	0
in	0
a	0
72	0
year	0
-	0
old	0
patient	0
with	0
subarachnoid	3
haemorrhage	4
(	0
SAH	3
)	0
is	0
described	0
.	0

Pathogenetic	0
hypotheses	0
are	0
discussed	0
.	0

Cerebral	3
hemorrhage	4
associated	0
with	0
phenylpropanolamine	1
in	0
combination	0
with	0
caffeine	1
.	0

Phenylpropanolamine	1
(	0
PPA	1
)	0
is	0
a	0
drug	0
that	0
has	0
been	0
associated	0
with	0
serious	0
side	0
effects	0
including	0
stroke	3
.	0

It	0
is	0
often	0
combined	0
with	0
caffeine	1
in	0
diet	0
preparations	0
and	0
"	0
look	0
-	0
alike	0
"	0
pills	0
.	0

In	0
order	0
to	0
determine	0
if	0
PPA	1
/	0
caffeine	1
can	0
lead	0
to	0
stroke	3
in	0
normotensive	0
and	0
/	0
or	0
hypertensive	3
rats	0
,	0
we	0
administered	0
the	0
combination	0
in	0
six	0
times	0
the	0
allowed	0
human	0
dose	0
calculated	0
on	0
a	0
per	0
weight	0
basis	0
for	0
the	0
rats	0
two	0
times	0
per	0
day	0
for	0
five	0
days	0
.	0

Subarachnoid	3
and	4
cerebral	4
hemorrhage	4
was	0
noted	0
in	0
18	0
%	0
of	0
the	0
hypertensive	3
rats	0
.	0

A	0
single	0
PPA	1
/	0
caffeine	1
administration	0
(	0
same	0
dose	0
)	0
lead	0
to	0
acute	0
hypertension	3
in	0
both	0
the	0
normotensive	0
and	0
hypertensive	3
animals	0
.	0

These	0
results	0
suggest	0
that	0
PPA	1
/	0
caffeine	1
can	0
lead	0
to	0
cerebral	3
hemorrhage	4
in	0
previously	0
hypertensive	3
animals	0
when	0
administered	0
in	0
greater	0
than	0
the	0
allowed	0
dosage	0
.	0

An	0
acute	0
elevation	0
in	0
blood	0
pressure	0
may	0
be	0
a	0
contributing	0
factor	0
.	0

Renal	3
papillary	4
necrosis	4
due	0
to	0
naproxen	1
.	0

A	0
31	0
-	0
year	0
-	0
old	0
man	0
with	0
rheumatoid	3
arthritis	4
,	0
who	0
had	0
previously	0
been	0
treated	0
with	0
sulindac	1
,	0
fenoprofen	1
calcium	2
,	0
high	0
dose	0
salicylates	1
and	0
gold	1
salts	0
,	0
developed	0
renal	3
papillary	4
necrosis	4
(	0
RPN	3
)	0
4	0
months	0
after	0
institution	0
of	0
naproxen	1
therapy	0
.	0

No	0
other	0
factor	0
predisposing	0
to	0
RPN	3
could	0
be	0
discovered	0
.	0

Sulindac	1
was	0
substituted	0
for	0
naproxen	1
and	0
no	0
further	0
adverse	0
renal	0
effects	0
occurred	0
over	0
the	0
next	0
12	0
months	0
.	0

We	0
review	0
previous	0
reports	0
linking	0
RPN	3
to	0
antiinflammatory	0
drug	0
use	0
and	0
discuss	0
possible	0
advantages	0
of	0
sulindac	1
in	0
patients	0
who	0
have	0
experienced	0
renal	3
toxicity	4
from	0
other	0
antiinflammatory	0
agents	0
.	0

Nephrotoxic	3
effects	0
of	0
aminoglycoside	1
treatment	0
on	0
renal	0
protein	0
reabsorption	0
and	0
accumulation	0
.	0

To	0
quantify	0
the	0
effects	0
of	0
gentamicin	1
,	0
kanamycin	1
and	0
netilmicin	1
on	0
renal	0
protein	0
reabsorption	0
and	0
accumulation	0
,	0
these	0
drugs	0
were	0
administered	0
to	0
rats	0
intraperitoneally	0
(	0
30	0
mg	0
/	0
kg	0
/	0
day	0
)	0
for	0
7	0
,	0
14	0
or	0
21	0
days	0
.	0

Scanning	0
electron	0
microscopy	0
of	0
the	0
glomerular	0
endothelia	0
,	0
urinary	0
measurements	0
of	0
sodium	1
,	0
potassium	1
,	0
endogenous	0
lysozyme	0
,	0
N	0
-	0
acetyl	0
-	0
beta	0
-	0
D	0
-	0
glucosaminidase	0
(	0
NAG	0
)	0
as	0
well	0
as	0
clearance	0
and	0
accumulation	0
experiments	0
after	0
i	0
.	0
v	0
.	0
administration	0
of	0
egg	0
-	0
white	0
lysozyme	0
and	0
measurements	0
of	0
inulin	0
clearance	0
(	0
GFR	0
)	0
were	0
done	0
in	0
each	0
treatment	0
group	0
.	0

Gentamicin	1
administration	0
decreased	0
diameter	0
,	0
density	0
and	0
shape	0
of	0
endothelial	0
fenestrae	0
.	0

Kanamycin	1
and	0
netilmicin	1
appeared	0
to	0
have	0
no	0
effect	0
at	0
the	0
dose	0
used	0
.	0

All	0
three	0
aminoglycosides	1
decreased	0
GFR	0
and	0
increased	0
urinary	0
excretion	0
of	0
sodium	1
and	0
potassium	1
.	0

While	0
gentamicin	1
and	0
kanamycin	1
decreased	0
the	0
percentage	0
reabsorption	0
and	0
accumulation	0
of	0
lysozyme	0
after	0
i	0
.	0
v	0
.	0
administration	0
of	0
egg	0
-	0
white	0
lysozyme	0
netilmicin	1
had	0
no	0
effect	0
.	0

Daily	0
excretion	0
of	0
total	0
protein	0
,	0
endogenous	0
lysozyme	0
and	0
NAG	0
increased	0
only	0
after	0
treatment	0
with	0
kanamycin	1
and	0
gentamicin	1
.	0

Thus	0
,	0
aminoglycosides	1
may	0
act	0
as	0
nephrotoxicants	0
at	0
glomerular	0
and	0
/	0
or	0
tubular	0
level	0
inducing	0
impairment	3
of	4
renal	4
reabsorption	4
and	0
accumulation	0
of	0
proteins	0
.	0

Induction	0
of	0
the	0
obstructive	3
sleep	4
apnea	4
syndrome	4
in	0
a	0
woman	0
by	0
exogenous	0
androgen	1
administration	0
.	0

We	0
documented	0
airway	0
occlusion	0
during	0
sleep	0
and	0
an	0
abnormally	0
high	0
supraglottic	0
resistance	0
while	0
awake	0
in	0
a	0
54	0
-	0
yr	0
-	0
old	0
woman	0
who	0
had	0
developed	0
physical	0
changes	0
and	0
the	0
syndrome	3
of	4
obstructive	4
sleep	4
apnea	4
while	0
being	0
administered	0
exogenous	0
androgens	1
.	0

When	0
the	0
androgens	1
were	0
withdrawn	0
,	0
the	0
patient	0
'	0
s	0
physical	0
changes	0
,	0
symptoms	0
,	0
sleep	0
study	0
,	0
and	0
supraglottic	0
resistance	0
all	0
returned	0
to	0
normal	0
.	0

A	0
rechallenge	0
with	0
androgen	1
produced	0
symptoms	0
of	0
obstructive	3
sleep	4
apnea	4
that	0
abated	0
upon	0
withdrawal	0
of	0
the	0
hormone	0
.	0

Previous	0
reports	0
have	0
favored	0
a	0
role	0
of	0
androgens	1
in	0
the	0
pathogenesis	0
of	0
sleep	3
apnea	4
.	0

0ur	0
report	0
provides	0
direct	0
evidence	0
for	0
this	0
role	0
.	0

Structural	0
and	0
functional	0
measurements	0
indicate	0
that	0
androgens	1
exert	0
a	0
permissive	0
or	0
necessary	0
action	0
on	0
the	0
structural	0
configuration	0
of	0
the	0
oropharynx	0
that	0
predisposes	0
to	0
obstruction	0
during	0
sleep	0
.	0

Development	0
of	0
the	0
obstructive	3
sleep	4
apnea	4
syndrome	4
must	0
be	0
considered	0
a	0
possible	0
side	0
effect	0
of	0
androgen	1
therapy	0
.	0

Cardiotoxic	3
and	0
possible	0
leukemogenic	0
effects	0
of	0
adriamycin	1
in	0
nonhuman	0
primates	0
.	0

10	0
monkeys	0
(	0
macaques	0
)	0
received	0
adriamycin	1
by	0
monthly	0
intravenous	0
injections	0
at	0
12	0
mg	0
/	0
m2	0
(	0
1	0
mg	0
/	0
kg	0
)	0
.	0

8	0
of	0
the	0
10	0
monkeys	0
developed	0
congestive	3
heart	4
failure	4
at	0
an	0
average	0
cumulative	0
adriamycin	1
dose	0
(	0
310	0
mg	0
/	0
m2	0
)	0
well	0
below	0
that	0
considered	0
the	0
safe	0
upper	0
limit	0
(	0
550	0
mg	0
/	0
m2	0
)	0
in	0
man	0
.	0

Histologically	0
,	0
the	0
myocardial	3
lesions	4
resembled	0
those	0
found	0
in	0
human	0
anthracycline	1
-	0
induced	0
cardiomyopathy	3
.	0

1	0
of	0
the	0
10	0
monkeys	0
developed	0
acute	3
myeloblastic	4
leukemia	4
after	0
receiving	0
324	0
mg	0
/	0
m2	0
of	0
adriamycin	1
;	0
the	0
10th	0
monkey	0
is	0
alive	0
and	0
well	0
26	0
months	0
after	0
the	0
last	0
dose	0
of	0
drug	0
.	0

0ur	0
results	0
suggest	0
that	0
adriamycin	1
is	0
a	0
more	0
potent	0
cardiotoxin	0
in	0
monkeys	0
than	0
in	0
man	0
,	0
and	0
that	0
leukemia	3
may	0
be	0
a	0
consequence	0
of	0
prolonged	0
treatment	0
with	0
this	0
drug	0
.	0

Tricuspid	3
valve	4
regurgitation	4
and	0
lithium	1
carbonate	2
toxicity	3
in	0
a	0
newborn	0
infant	0
.	0

A	0
newborn	0
with	0
massive	0
tricuspid	3
regurgitation	4
,	0
atrial	3
flutter	4
,	0
congestive	3
heart	4
failure	4
,	0
and	0
a	0
high	0
serum	0
lithium	1
level	0
is	0
described	0
.	0

This	0
is	0
the	0
first	0
patient	0
to	0
initially	0
manifest	0
tricuspid	3
regurgitation	4
and	0
atrial	3
flutter	4
,	0
and	0
the	0
11th	0
described	0
patient	0
with	0
cardiac	3
disease	4
among	0
infants	0
exposed	0
to	0
lithium	1
compounds	0
in	0
the	0
first	0
trimester	0
of	0
pregnancy	0
.	0

Sixty	0
-	0
three	0
percent	0
of	0
these	0
infants	0
had	0
tricuspid	0
valve	0
involvement	0
.	0

Lithium	1
carbonate	2
may	0
be	0
a	0
factor	0
in	0
the	0
increasing	0
incidence	0
of	0
congenital	3
heart	4
disease	4
when	0
taken	0
during	0
early	0
pregnancy	0
.	0

It	0
also	0
causes	0
neurologic	3
depression	4
,	0
cyanosis	3
,	0
and	0
cardiac	3
arrhythmia	4
when	0
consumed	0
prior	0
to	0
delivery	0
.	0

Effects	0
of	0
the	0
novel	0
compound	0
aniracetam	1
(	0
Ro	1
13	2
-	2
5057	2
)	0
upon	0
impaired	3
learning	4
and	4
memory	4
in	0
rodents	0
.	0

The	0
effect	0
of	0
aniracetam	1
(	0
Ro	1
13	2
-	2
5057	2
,	0
1	1
-	2
anisoyl	2
-	2
2	2
-	2
pyrrolidinone	2
)	0
was	0
studied	0
on	0
various	0
forms	0
of	0
experimentally	0
impaired	3
cognitive	4
functions	4
(	0
learning	0
and	0
memory	0
)	0
in	0
rodents	0
and	0
produced	0
the	0
following	0
effects	0
:	0
(	0
1	0
)	0
almost	0
complete	0
prevention	0
of	0
the	0
incapacity	0
to	0
learn	0
a	0
discrete	0
escape	0
response	0
in	0
rats	0
exposed	0
to	0
sublethal	0
hypercapnia	3
immediately	0
before	0
the	0
acquisition	0
session	0
;	0
(	0
2	0
)	0
partial	0
(	0
rats	0
)	0
or	0
complete	0
(	0
mice	0
)	0
prevention	0
of	0
the	0
scopolamine	1
-	0
induced	0
short	0
-	0
term	0
amnesia	3
for	0
a	0
passive	0
avoidance	0
task	0
;	0
(	0
3	0
)	0
complete	0
protection	0
against	0
amnesia	3
for	0
a	0
passive	0
avoidance	0
task	0
in	0
rats	0
submitted	0
to	0
electroconvulsive	0
shock	0
immediately	0
after	0
avoidance	0
acquisition	0
;	0
(	0
4	0
)	0
prevention	0
of	0
the	0
long	0
-	0
term	0
retention	0
-	0
or	0
retrieval	0
-	0
deficit	0
for	0
a	0
passive	0
avoidance	0
task	0
induced	0
in	0
rats	0
and	0
mice	0
by	0
chloramphenicol	1
or	0
cycloheximide	1
administered	0
immediately	0
after	0
acquisition	0
;	0
(	0
5	0
)	0
reversal	0
,	0
when	0
administered	0
as	0
late	0
as	0
1	0
h	0
before	0
the	0
retention	0
test	0
,	0
of	0
the	0
deficit	0
in	0
retention	0
or	0
retrieval	0
of	0
a	0
passive	0
avoidance	0
task	0
induced	0
by	0
cycloheximide	1
injected	0
2	0
days	0
previously	0
;	0
(	0
6	0
)	0
prevention	0
of	0
the	0
deficit	0
in	0
the	0
retrieval	0
of	0
an	0
active	0
avoidance	0
task	0
induced	0
in	0
mice	0
by	0
subconvulsant	0
electroshock	0
or	0
hypercapnia	3
applied	0
immediately	0
before	0
retrieval	0
testing	0
(	0
24	0
h	0
after	0
acquisition	0
)	0
.	0

These	0
improvements	0
or	0
normalizations	0
of	0
impaired	3
cognitive	4
functions	4
were	0
seen	0
at	0
oral	0
aniracetam	1
doses	0
of	0
10	0
-	0
100	0
mg	0
/	0
kg	0
.	0

Generally	0
,	0
the	0
dose	0
-	0
response	0
curves	0
were	0
bell	0
-	0
shaped	0
.	0

The	0
mechanisms	0
underlying	0
the	0
activity	0
of	0
aniracetam	1
and	0
its	0
'	0
therapeutic	0
window	0
'	0
are	0
unknown	0
.	0

Piracetam	1
,	0
another	0
pyrrolidinone	1
derivative	0
was	0
used	0
for	0
comparison	0
.	0

It	0
was	0
active	0
only	0
in	0
six	0
of	0
nine	0
tests	0
and	0
had	0
about	0
one	0
-	0
tenth	0
the	0
potency	0
of	0
aniracetam	1
.	0

The	0
results	0
indicate	0
that	0
aniracetam	1
improves	0
cognitive	0
functions	0
which	0
are	0
impaired	0
by	0
different	0
procedure	0
and	0
in	0
different	0
phases	0
of	0
the	0
learning	0
and	0
memory	0
process	0
.	0

Effect	0
of	0
calcium	1
chloride	2
on	0
gross	0
behavioural	0
changes	0
produced	0
by	0
carbachol	1
and	0
eserine	1
in	0
cats	0
.	0

The	0
effect	0
of	0
calcium	1
chloride	2
injected	0
into	0
the	0
cerebral	0
ventricles	0
of	0
group	0
-	0
housed	0
unanaesthetized	0
cats	0
upon	0
vocalization	0
(	0
rage	0
,	0
hissing	0
and	0
snarling	0
)	0
,	0
fighting	0
(	0
attack	0
with	0
paws	0
and	0
claws	0
,	0
defense	0
with	0
paws	0
and	0
claws	0
and	0
biting	0
)	0
,	0
mydriasis	3
,	0
tremor	3
and	0
clonic	3
-	4
tonic	4
convulsions	4
produced	0
by	0
carbachol	1
and	0
eserine	1
injected	0
similarly	0
was	0
investigated	0
.	0

Calcium	1
chloride	2
depressed	0
or	0
almost	0
completely	0
abolished	0
the	0
vocalization	0
and	0
fighting	0
due	0
to	0
carbachol	1
and	0
eserine	1
.	0

0n	0
the	0
other	0
hand	0
,	0
mydriasis	3
,	0
tremor	3
and	0
clonic	3
-	4
tonic	4
convulsions	4
evoked	0
by	0
carbachol	1
and	0
eserine	1
were	0
not	0
significantly	0
changed	0
by	0
calcium	1
chloride	2
.	0

It	0
is	0
apparent	0
that	0
calcium	1
chloride	2
can	0
"	0
dissociate	0
"	0
vocalization	0
and	0
fighting	0
from	0
autonomic	0
and	0
motor	0
phenomena	0
such	0
as	0
mydriasis	3
,	0
tremor	3
and	0
clonic	3
-	4
tonic	4
convulsions	4
caused	0
by	0
carbachol	1
and	0
eserine	1
.	0

Calcium	1
chloride	2
inhibited	0
the	0
vocalization	0
and	0
fighting	0
produced	0
by	0
carbachol	1
and	0
eserine	1
most	0
probably	0
by	0
a	0
nonspecific	0
stabilizing	0
action	0
on	0
central	0
muscarinic	0
cholinoceptive	0
sites	0
.	0

These	0
results	0
further	0
support	0
the	0
view	0
that	0
calcium	1
ions	0
in	0
excess	0
have	0
an	0
atropine	1
-	0
like	0
action	0
also	0
in	0
the	0
central	0
nervous	0
system	0
.	0

Thiazide	1
diuretics	0
,	0
hypokalemia	3
and	0
cardiac	3
arrhythmias	4
.	0

Thiazide	1
diuretics	0
are	0
widely	0
accepted	0
as	0
the	0
cornerstone	0
of	0
antihypertensive	0
treatment	0
programs	0
.	0

Hypokalemia	3
is	0
a	0
commonly	0
encountered	0
metabolic	0
consequence	0
of	0
chronic	0
thiazide	1
therapy	0
.	0

We	0
treated	0
38	0
patients	0
(	0
22	0
low	0
renin	0
,	0
16	0
normal	0
renin	0
)	0
with	0
moderate	0
diastolic	3
hypertension	4
with	0
hydrochlorothiazide	1
(	0
HCTC	1
)	0
administered	0
on	0
a	0
twice	0
daily	0
schedule	0
.	0

Initial	0
dose	0
was	0
50	0
mg	0
and	0
the	0
dose	0
was	0
increased	0
at	0
monthly	0
intervals	0
to	0
100	0
mg	0
,	0
150	0
mg	0
and	0
200	0
mg	0
daily	0
until	0
blood	0
pressure	0
normalized	0
.	0

The	0
serum	0
K	1
during	0
the	0
control	0
period	0
was	0
4	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
2	0
mEq	0
/	0
l	0
an	0
on	0
50	0
,	0
100	0
,	0
150	0
and	0
200	0
mg	0
HCTZ	1
daily	0
3	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
3	0
,	0
3	0
.	0
4	0
+	0
/	0
-	0
0	0
.	0
2	0
,	0
2	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
2	0
,	0
and	0
2	0
.	0
4	0
+	0
/	0
-	0
0	0
.	0
3	0
mEq	0
/	0
l	0
,	0
respectively	0
.	0

Corresponding	0
figures	0
for	0
whole	0
body	0
K	1
were	0
4107	0
+	0
/	0
-	0
208	0
,	0
3722	0
+	0
/	0
-	0
319	0
,	0
3628	0
+	0
/	0
-	0
257	0
,	0
3551	0
+	0
/	0
-	0
336	0
,	0
and	0
3269	0
+	0
/	0
-	0
380	0
mEq	0
,	0
respectively	0
.	0

In	0
13	0
patients	0
we	0
observed	0
the	0
effects	0
of	0
HCTZ	1
therapy	0
(	0
100	0
mg	0
daily	0
)	0
on	0
the	0
occurrence	0
of	0
PVC	0
'	0
s	0
during	0
rest	0
as	0
well	0
as	0
during	0
static	0
and	0
dynamic	0
exercise	0
.	0

During	0
rest	0
we	0
observed	0
0	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
08	0
PVC	0
beats	0
/	0
min	0
+	0
/	0
-	0
SEM	0
and	0
during	0
static	0
and	0
dynamic	0
exercise	0
0	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
06	0
and	0
0	0
.	0
8	0
+	0
/	0
-	0
0	0
.	0
15	0
,	0
respectively	0
.	0

Corresponding	0
figures	0
during	0
HCTZ	1
therapy	0
100	0
mg	0
daily	0
were	0
1	0
.	0
4	0
+	0
/	0
-	0
0	0
.	0
1	0
,	0
3	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
7	0
and	0
5	0
.	0
7	0
4	0
/	0
-	0
0	0
.	0
8	0
,	0
respectively	0
.	0

The	0
occurrence	0
of	0
PVC	0
'	0
s	0
correlated	0
significantly	0
with	0
the	0
fall	0
in	0
serum	0
K	1
+	0
observed	0
r	0
=	0
0	0
.	0
72	0
,	0
p	0
less	0
than	0
0	0
.	0
001	0
.	0

In	0
conclusion	0
we	0
found	0
that	0
thiazide	1
diuretics	0
cause	0
hypokalemia	3
and	0
depletion	0
of	0
body	0
potassium	1
.	0

The	0
more	0
profound	0
hypokalemia	3
,	0
the	0
greater	0
the	0
propensity	0
for	0
the	0
occurrence	0
of	0
PVC	0
'	0
s	0
.	0

Circulating	0
lysosomal	0
enzymes	0
and	0
acute	3
hepatic	4
necrosis	4
.	0

The	0
activities	0
of	0
the	0
lysosomal	0
enzymes	0
acid	0
and	0
neutral	0
protease	0
,	0
N	0
-	0
acetylglucosaminidase	0
,	0
and	0
acid	0
phosphatase	0
were	0
measured	0
in	0
the	0
serum	0
of	0
patients	0
with	0
fulminant	3
hepatic	4
failure	4
.	0

Acid	0
protease	0
(	0
cathepsin	0
D	0
)	0
activity	0
was	0
increased	0
about	0
tenfold	0
in	0
patients	0
who	0
died	0
and	0
nearly	0
fourfold	0
in	0
those	0
who	0
survived	0
fulminant	3
hepatic	4
failure	4
after	0
paracetamol	1
overdose	3
,	0
whereas	0
activities	0
were	0
increased	0
equally	0
in	0
patients	0
with	0
fulminant	3
hepatic	4
failure	4
due	0
to	0
viral	3
hepatitis	4
whether	0
or	0
not	0
they	0
survived	0
.	0

A	0
correlation	0
was	0
found	0
between	0
serum	0
acid	0
protease	0
activity	0
and	0
prothrombin	0
time	0
,	0
and	0
the	0
increase	0
in	0
cathepsin	0
D	0
activity	0
was	0
sustained	0
over	0
several	0
days	0
compared	0
with	0
aspartate	1
aminotransferase	0
,	0
which	0
showed	0
a	0
sharp	0
early	0
peak	0
and	0
then	0
a	0
fall	0
.	0

Circulating	0
lysosomal	0
proteases	0
can	0
damage	0
other	0
organs	0
,	0
and	0
measurement	0
of	0
their	0
activity	0
may	0
therefore	0
be	0
of	0
added	0
value	0
in	0
assessing	0
prognosis	0
in	0
this	0
condition	0
.	0

Hepatic	3
veno	4
-	4
occlusive	4
disease	4
caused	0
by	0
6	1
-	2
thioguanine	2
.	0

Clinically	0
reversible	0
veno	3
-	4
occlusive	4
disease	4
of	4
the	4
liver	4
developed	0
in	0
a	0
23	0
-	0
year	0
-	0
old	0
man	0
with	0
acute	3
lymphocytic	4
leukemia	4
after	0
10	0
months	0
of	0
maintenance	0
therapy	0
with	0
6	1
-	2
thioguanine	2
.	0

Serial	0
liver	0
biopsies	0
showed	0
the	0
development	0
and	0
resolution	0
of	0
intense	0
sinusoidal	0
engorgement	0
.	0

Although	0
this	0
disease	0
was	0
clinically	0
reversible	0
,	0
some	0
subintimal	0
fibrosis	3
about	0
the	0
terminal	0
hepatic	0
veins	0
persisted	0
.	0

This	0
case	0
presented	0
a	0
unique	0
opportunity	0
to	0
observe	0
the	0
histologic	0
features	0
of	0
clinically	0
reversible	0
hepatic	3
veno	4
-	4
occlusive	4
disease	4
over	0
time	0
,	0
and	0
may	0
be	0
the	0
first	0
case	0
of	0
veno	0
-	0
occlusive	0
related	0
solely	0
to	0
6	1
-	2
thioguanine	2
.	0

Chlorpropamide	1
-	0
induced	0
optic	3
neuropathy	4
.	0

A	0
65	0
-	0
year	0
-	0
old	0
woman	0
with	0
adult	3
-	4
onset	4
diabetes	4
treated	0
with	0
chlorpropamide	1
(	0
Diabenese	1
)	0
had	0
a	0
toxic	3
optic	4
neuropathy	4
that	0
resolved	0
with	0
discontinuation	0
of	0
chlorpropamide	1
therapy	0
.	0

Visual	3
loss	4
occurs	0
in	0
diabetics	3
for	0
a	0
variety	0
of	0
reasons	0
,	0
and	0
accurate	0
diagnosis	0
is	0
necessary	0
to	0
institute	0
appropriate	0
therapy	0
.	0

The	0
possibility	0
of	0
a	0
drug	0
-	0
induced	0
optic	3
neuropathy	4
should	0
be	0
considered	0
in	0
the	0
differential	0
diagnosis	0
of	0
visual	3
loss	4
in	0
diabetics	3
.	0

Plasma	0
and	0
urinary	0
lipids	0
and	0
lipoproteins	0
during	0
the	0
development	0
of	0
nephrotic	3
syndrome	4
induced	0
in	0
the	0
rat	0
by	0
puromycin	1
aminonucleoside	2
.	0

This	0
study	0
was	0
undertaken	0
to	0
ascertain	0
whether	0
the	0
alterations	0
of	0
plasma	0
lipoproteins	0
found	0
in	0
nephrotic	3
syndrome	4
induced	0
by	0
puromycin	1
aminonucleoside	2
were	0
due	0
to	0
nephrotic	3
syndrome	4
per	0
se	0
,	0
or	0
,	0
at	0
least	0
in	0
part	0
,	0
to	0
the	0
aminonucleoside	1
.	0

The	0
purpose	0
of	0
the	0
present	0
study	0
was	0
to	0
investigate	0
the	0
changes	0
in	0
plasma	0
and	0
urinary	0
lipoproteins	0
during	0
the	0
administration	0
of	0
puromycin	1
aminonucleoside	2
(	0
20	0
mg	0
/	0
kg	0
for	0
7	0
days	0
)	0
and	0
the	0
subsequent	0
development	0
of	0
nephrotic	3
syndrome	4
.	0

Since	0
massive	0
albuminuria	3
occurred	0
after	0
6	0
days	0
of	0
treatment	0
,	0
the	0
time	0
-	0
course	0
study	0
was	0
divided	0
into	0
two	0
stages	0
:	0
pre	0
-	0
nephrotic	3
stage	0
(	0
day	0
1	0
-	0
5	0
)	0
and	0
nephrotic	3
stage	0
(	0
day	0
6	0
-	0
11	0
)	0
.	0

In	0
pre	0
-	0
nephrotic	3
stage	0
the	0
plasma	0
level	0
of	0
fatty	1
acids	2
,	0
triacylglycerol	1
and	0
VLDL	0
decreased	0
while	0
that	0
of	0
phospholipid	0
,	0
cholesteryl	1
esters	2
and	0
HDL	0
remained	0
constant	0
.	0

Plasma	0
apolipoprotein	0
A	0
-	0
I	0
tended	0
to	0
increase	0
(	0
40	0
%	0
increase	0
at	0
day	0
5	0
)	0
.	0

At	0
the	0
beginning	0
of	0
nephrotic	3
stage	0
(	0
day	0
6	0
)	0
the	0
concentration	0
of	0
plasma	0
albumin	0
dropped	0
to	0
a	0
very	0
low	0
level	0
,	0
while	0
that	0
of	0
apolipoprotein	0
A	0
-	0
I	0
increased	0
abruptly	0
(	0
4	0
-	0
fold	0
increase	0
)	0
and	0
continued	0
to	0
rise	0
,	0
although	0
less	0
steeply	0
,	0
in	0
the	0
following	0
days	0
.	0

The	0
plasma	0
concentration	0
of	0
HDL	0
followed	0
the	0
same	0
pattern	0
.	0

Plasma	0
VLDL	0
and	0
LDL	0
increased	0
at	0
a	0
later	0
stage	0
(	0
day	0
9	0
)	0
.	0

Plasma	0
apolipoprotein	0
A	0
-	0
I	0
was	0
found	0
not	0
only	0
in	0
HDL	0
(	0
1	0
.	0
063	0
-	0
1	0
.	0
210	0
g	0
/	0
ml	0
)	0
but	0
also	0
in	0
the	0
LDL	0
density	0
class	0
(	0
1	0
.	0
025	0
-	0
1	0
.	0
050	0
g	0
/	0
ml	0
)	0
.	0

In	0
the	0
pre	0
-	0
nephrotic	3
stage	0
lipoproteinuria	0
was	0
negligible	0
,	0
while	0
in	0
the	0
early	0
nephrotic	3
stage	0
the	0
urinary	0
loss	0
of	0
plasma	0
lipoproteins	0
consisted	0
mainly	0
of	0
HDL	0
.	0

These	0
observations	0
indicate	0
that	0
puromycin	1
aminonucleoside	2
alters	0
plasma	0
lipoproteins	0
by	0
lowering	0
VLDL	0
and	0
increasing	0
HDL	0
.	0

It	0
is	0
likely	0
that	0
the	0
early	0
and	0
striking	0
increase	0
of	0
plasma	0
HDL	0
found	0
in	0
nephrotic	3
rats	0
is	0
related	0
to	0
a	0
direct	0
effect	0
of	0
the	0
drug	0
on	0
HDL	0
metabolism	0
.	0

Fatal	0
aplastic	3
anemia	4
following	0
topical	0
administration	0
of	0
ophthalmic	0
chloramphenicol	1
.	0

A	0
73	0
-	0
year	0
-	0
old	0
woman	0
died	0
of	0
aplastic	3
anemia	4
less	0
than	0
two	0
months	0
after	0
undergoing	0
cataract	3
extraction	0
and	0
beginning	0
topical	0
therapy	0
with	0
chloramphenicol	1
.	0

The	0
first	0
signs	0
of	0
pancytopenia	3
began	0
within	0
one	0
month	0
of	0
the	0
surgery	0
.	0

The	0
pattern	0
of	0
the	0
aplastic	3
anemia	4
was	0
associated	0
with	0
an	0
idiosyncratic	0
response	0
to	0
chloramphenicol	1
.	0

This	0
was	0
the	0
second	0
report	0
of	0
fatal	0
aplastic	3
anemia	4
after	0
topical	0
treatment	0
with	0
chloramphenicol	1
for	0
ocular	0
conditions	0
,	0
although	0
two	0
cases	0
of	0
reversible	0
bone	3
marrow	4
hypoplasia	4
have	0
also	0
been	0
reported	0
.	0

Any	0
other	0
suspected	0
cases	0
of	0
ocular	3
toxicity	4
associated	0
with	0
topically	0
applied	0
chloramphenicol	1
should	0
be	0
reported	0
to	0
the	0
National	0
Registry	0
of	0
Drug	0
-	0
Induced	0
0cular	0
Side	0
Effects	0
,	0
0regon	0
Health	0
Sciences	0
University	0
,	0
Portland	0
,	0
0R	0
97201	0
.	0

Midazolam	1
compared	0
with	0
thiopentone	1
as	0
an	0
induction	0
agent	0
.	0

In	0
patients	0
premedicated	0
with	0
scopolamine	1
+	0
morphine	1
(	0
+	0
5	0
mg	0
nitrazepam	1
the	0
evening	0
before	0
surgery	0
)	0
,	0
the	0
sleep	0
-	0
inducing	0
effect	0
of	0
midazolam	1
0	0
.	0
15	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
was	0
clearly	0
slower	0
in	0
onset	0
than	0
that	0
of	0
thiopentone	1
4	0
.	0
67	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
Somewhat	0
fewer	0
cardiovascular	0
and	0
local	0
sequelae	0
were	0
found	0
in	0
the	0
midazolam	1
group	0
,	0
but	0
,	0
although	0
apnoea	3
occurred	0
less	0
often	0
in	0
the	0
midazolam	1
group	0
it	0
lasted	0
longer	0
.	0

0n	0
the	0
whole	0
,	0
the	0
differences	0
between	0
midazolam	1
and	0
thiopentone	1
had	0
no	0
apparent	0
clinical	0
consequences	0
.	0

Midazolam	1
is	0
a	0
new	0
alternative	0
agent	0
for	0
induction	0
in	0
combination	0
anaesthesia	0
.	0

Extrapyramidal	0
side	0
effects	0
and	0
oral	0
haloperidol	1
:	0
an	0
analysis	0
of	0
explanatory	0
patient	0
and	0
treatment	0
characteristics	0
.	0

The	0
incidence	0
of	0
extrapyramidal	0
side	0
effects	0
(	0
EPS	0
)	0
was	0
evaluated	0
in	0
98	0
patients	0
treated	0
with	0
haloperidol	1
.	0

The	0
incidence	0
of	0
parkinsonism	3
was	0
higher	0
at	0
higher	0
doses	0
of	0
haloperidol	1
and	0
in	0
younger	0
patients	0
.	0

Prophylactic	0
antiparkinsonian	0
medication	0
was	0
effective	0
in	0
younger	0
but	0
not	0
in	0
older	0
patients	0
.	0

However	0
,	0
these	0
medications	0
were	0
more	0
effective	0
in	0
both	0
young	0
and	0
old	0
patients	0
when	0
given	0
after	0
parkinsonism	3
developed	0
.	0

Akathisia	3
was	0
controlled	0
by	0
the	0
benzodiazepine	1
lorazepam	1
in	0
14	0
out	0
of	0
16	0
patients	0
,	0
while	0
prophylactic	0
antiparkinsonians	0
were	0
ineffective	0
.	0

The	0
present	0
study	0
points	0
to	0
patient	0
characteristics	0
that	0
may	0
be	0
of	0
significance	0
in	0
the	0
development	0
of	0
EPS	0
due	0
to	0
haloperidol	1
.	0

Deaths	0
from	0
local	0
anesthetic	0
-	0
induced	0
convulsions	3
in	0
mice	0
.	0

Median	0
convulsant	0
(	0
CD50	0
)	0
and	0
median	0
lethal	0
(	0
LD50	0
)	0
doses	0
of	0
three	0
representative	0
local	0
anesthetics	0
were	0
determined	0
in	0
adult	0
mice	0
to	0
evaluate	0
the	0
threat	0
to	0
life	0
of	0
local	0
anesthetic	0
-	0
induced	0
convulsions	3
.	0

The	0
CD50	0
and	0
LD50	0
,	0
respectively	0
,	0
were	0
57	0
.	0
7	0
and	0
58	0
.	0
7	0
mg	0
/	0
kg	0
for	0
bupivacaine	1
,	0
111	0
.	0
0	0
and	0
133	0
.	0
1	0
mg	0
/	0
kg	0
for	0
lidocaine	1
,	0
and	0
243	0
.	0
4	0
and	0
266	0
.	0
5	0
mg	0
/	0
kg	0
for	0
chloroprocaine	1
.	0

When	0
given	0
intraperitoneally	0
,	0
bupivacaine	1
thus	0
was	0
only	0
about	0
twice	0
as	0
toxic	0
as	0
lidocaine	1
and	0
four	0
times	0
as	0
toxic	0
as	0
chloroprocaine	1
.	0

Convulsions	3
always	0
preceded	0
death	0
,	0
except	0
after	0
precipitous	0
cardiopulmonary	3
arrest	4
from	0
extreme	0
doses	0
.	0

A	0
CD50	0
dose	0
of	0
local	0
anesthetic	0
(	0
causing	0
convulsions	3
in	0
50	0
%	0
of	0
mice	0
)	0
was	0
fatal	0
in	0
90	0
%	0
of	0
bupivacaine	1
-	0
induced	0
seizures	3
,	0
in	0
57	0
%	0
of	0
the	0
chloroprocaine	1
group	0
,	0
and	0
in	0
6	0
%	0
of	0
the	0
lidocaine	1
group	0
.	0

The	0
narrow	0
gap	0
between	0
convulsant	0
and	0
lethal	0
doses	0
of	0
local	0
anesthetics	0
indicates	0
that	0
untreated	0
convulsions	3
present	0
much	0
more	0
of	0
a	0
threat	0
to	0
life	0
than	0
heretofore	0
appreciated	0
.	0

REM	3
sleep	4
deprivation	4
changes	0
behavioral	0
response	0
to	0
catecholaminergic	0
and	0
serotonergic	0
receptor	0
activation	0
in	0
rats	0
.	0

The	0
effects	0
of	0
REM	3
sleep	4
deprivation	4
(	0
REMD	3
)	0
on	0
apomorphine	1
-	0
induced	0
aggressiveness	3
and	0
quipazine	1
-	0
induced	0
head	3
twitches	4
in	0
rats	0
were	0
determined	0
.	0

Forty	0
-	0
eight	0
hr	0
of	0
REMD	3
increased	0
apomorphine	1
-	0
induced	0
aggressiveness	3
,	0
and	0
reduced	0
(	0
immediately	0
after	0
completing	0
of	0
REMD	3
)	0
or	0
increased	0
(	0
96	0
hr	0
after	0
completing	0
of	0
REMD	3
)	0
quipazine	1
-	0
induced	0
head	3
twitches	4
.	0

Results	0
are	0
discussed	0
in	0
terms	0
of	0
similarity	0
to	0
pharmacological	0
effects	0
of	0
other	0
antidepressive	0
treatments	0
.	0

Fatal	0
aplastic	3
anemia	4
due	0
to	0
indomethacin	1
-	0
-	0
lymphocyte	0
transformation	0
tests	0
in	0
vitro	0
.	0

Although	0
indomethacin	1
has	0
been	0
implicated	0
as	0
a	0
possible	0
cause	0
of	0
aplastic	3
anemia	4
on	0
the	0
basis	0
of	0
a	0
few	0
clinical	0
observations	0
,	0
its	0
role	0
has	0
not	0
been	0
definitely	0
established	0
.	0

A	0
case	0
of	0
fatal	0
aplastic	3
anemia	4
is	0
described	0
in	0
which	0
no	0
drugs	0
other	0
than	0
allopurinol	1
and	0
indomethacin	1
were	0
given	0
.	0

Indomethacin	1
was	0
first	0
given	0
four	0
weeks	0
prior	0
to	0
the	0
onset	0
of	0
symptoms	0
.	0

A	0
positive	0
lymphocyte	0
transformation	0
test	0
with	0
indomethacin	1
in	0
vitro	0
further	0
substantiates	0
the	0
potential	0
role	0
of	0
this	0
drug	0
in	0
causing	0
aplastic	3
anemia	4
in	0
a	0
susceptible	0
patient	0
.	0

Fortunately	0
,	0
this	0
seems	0
to	0
be	0
a	0
very	0
rare	0
complication	0
.	0

Dose	0
-	0
effect	0
and	0
structure	0
-	0
function	0
relationships	0
in	0
doxorubicin	1
cardiomyopathy	3
.	0

The	0
cardiomyopathy	3
(	0
CM	3
)	0
produced	0
by	0
the	0
anticancer	0
drug	0
doxorubicin	1
(	0
DXR	1
)	0
(	0
Adriamycin	1
)	0
provides	0
a	0
unique	0
opportunity	0
to	0
analyze	0
dose	0
-	0
effect	0
and	0
structure	0
-	0
function	0
relationships	0
during	0
development	0
of	0
myocardial	3
disease	4
.	0

We	0
measured	0
the	0
degree	0
of	0
morphologic	0
damage	0
by	0
ultrastructural	0
examination	0
of	0
endomyocardial	0
biopsy	0
and	0
the	0
degree	0
of	0
performance	0
abnormally	0
by	0
right	0
heart	0
catheterization	0
in	0
patients	0
receiving	0
DXR	1
.	0

Morphologic	0
damage	0
was	0
variable	0
but	0
was	0
proportional	0
to	0
the	0
total	0
cumulative	0
DXR	1
dose	0
between	0
100	0
and	0
600	0
mg	0
/	0
m2	0
.	0

Performance	0
abnormalities	0
correlated	0
weakly	0
with	0
dose	0
,	0
exhibited	0
a	0
curvilinear	0
relationship	0
,	0
and	0
had	0
a	0
"	0
threshold	0
"	0
for	0
expression	0
.	0

Catheterization	0
abnormalities	0
correlated	0
well	0
with	0
morphologic	0
damage	0
(	0
r	0
=	0
0	0
.	0
57	0
to	0
0	0
.	0
78	0
)	0
in	0
a	0
subgroup	0
of	0
patients	0
in	0
whom	0
exercise	0
hemodynamics	0
were	0
measured	0
,	0
and	0
this	0
relationship	0
also	0
exhibited	0
a	0
curvilinear	0
,	0
threshold	0
configuration	0
.	0

In	0
DXR	1
-	0
CM	3
myocardial	3
damage	4
is	0
proportional	0
to	0
the	0
degree	0
of	0
cytotoxic	0
insult	0
(	0
DXR	1
dose	0
)	0
while	0
myocardial	0
function	0
is	0
preserved	0
until	0
a	0
critical	0
dose	0
or	0
degree	0
of	0
damage	0
is	0
reached	0
,	0
after	0
which	0
myocardial	0
performance	0
deteriorates	0
rapidly	0
.	0

Massive	0
cerebral	3
edema	4
associated	0
with	0
fulminant	0
hepatic	3
failure	4
in	0
acetaminophen	1
overdose	3
:	0
possible	0
role	0
of	0
cranial	0
decompression	0
.	0

Cerebral	3
edema	4
may	0
complicate	0
the	0
course	0
of	0
fulminant	3
hepatic	4
failure	4
.	0

Response	0
to	0
conventional	0
therapy	0
has	0
been	0
disappointing	0
.	0

We	0
present	0
a	0
patient	0
with	0
fatal	0
acetaminophen	1
-	0
induced	0
fulminant	3
hepatic	4
failure	4
,	0
with	0
signs	0
and	0
symptoms	0
of	0
cerebral	3
edema	4
,	0
unresponsive	0
to	0
conventional	0
medical	0
therapy	0
.	0

Cranial	0
decompression	0
was	0
carried	0
out	0
.	0

A	0
justification	0
of	0
the	0
need	0
for	0
further	0
evaluation	0
of	0
cranial	0
decompression	0
in	0
such	0
patients	0
is	0
presented	0
.	0

Subjective	0
assessment	0
of	0
sexual	3
dysfunction	4
of	0
patients	0
on	0
long	0
-	0
term	0
administration	0
of	0
digoxin	1
.	0

Various	0
data	0
suggest	0
that	0
male	0
patients	0
who	0
have	0
received	0
digoxin	1
on	0
a	0
longterm	0
basis	0
have	0
increased	0
levels	0
of	0
serum	0
estrogen	1
and	0
decreased	0
levels	0
of	0
plasma	0
testosterone	1
and	0
luteinizing	0
hormone	0
(	0
LH	0
)	0
.	0

This	0
study	0
was	0
undertaken	0
to	0
investigate	0
the	0
links	0
between	0
the	0
long	0
-	0
term	0
administration	0
of	0
digoxin	1
therapy	0
and	0
sexual	0
behavior	0
,	0
and	0
the	0
effect	0
of	0
digoxin	1
on	0
plasma	0
levels	0
of	0
estradiol	1
,	0
testosterone	1
,	0
and	0
LH	0
.	0

The	0
patients	0
of	0
the	0
study	0
and	0
control	0
group	0
(	0
without	0
digoxin	1
)	0
were	0
of	0
similar	0
cardiac	0
functional	0
capacity	0
and	0
age	0
(	0
25	0
-	0
40	0
years	0
)	0
and	0
were	0
randomly	0
selected	0
from	0
the	0
rheumatic	3
heart	4
disease	4
patients	0
.	0

A	0
subjective	0
assessment	0
of	0
sexual	0
behavior	0
in	0
the	0
study	0
and	0
control	0
groups	0
was	0
carried	0
out	0
,	0
using	0
parameters	0
such	0
as	0
sexual	0
desire	0
,	0
sexual	0
excitement	0
,	0
and	0
frequency	0
of	0
sexual	0
relations	0
.	0

Personal	0
interviews	0
and	0
a	0
questionnaire	0
were	0
also	0
used	0
for	0
the	0
evaluation	0
of	0
sexual	0
behavior	0
.	0

The	0
findings	0
support	0
the	0
reports	0
concerning	0
digoxin	1
effect	0
on	0
plasma	0
estradiol	1
,	0
testosterone	1
,	0
and	0
LH	0
.	0

The	0
differences	0
in	0
the	0
means	0
were	0
significant	0
.	0

Tests	0
used	0
to	0
evaluate	0
the	0
changes	0
in	0
sexual	0
behavior	0
showed	0
a	0
significant	0
decrease	3
in	4
sexual	4
desire	4
,	0
sexual	0
excitement	0
phase	0
(	0
erection	0
)	0
,	0
and	0
frequency	0
of	0
sexual	0
relations	0
in	0
the	0
study	0
group	0
.	0

Endometrial	3
carcinoma	4
after	0
Hodgkin	3
disease	4
in	0
childhood	0
.	0

A	0
34	0
-	0
year	0
-	0
old	0
patient	0
developed	0
metastic	0
endometrial	3
carcinoma	4
after	0
Hodgkin	3
disease	4
in	0
childhood	0
.	0

She	0
had	0
ovarian	3
failure	4
after	0
abdominal	0
irradiation	0
and	0
chemotherapy	0
for	0
Hodgkin	3
disease	4
,	0
and	0
received	0
exogenous	0
estrogens	1
,	0
a	0
treatment	0
implicated	0
in	0
the	0
development	0
of	0
endometrial	3
cancer	4
in	0
menopausal	0
women	0
.	0

Young	0
women	0
on	0
replacement	0
estrogens	1
for	0
ovarian	3
failure	4
after	0
cancer	3
therapy	0
may	0
also	0
have	0
increased	0
risk	0
of	0
endometrial	3
carcinoma	4
and	0
should	0
be	0
examined	0
periodically	0
.	0

Long	0
-	0
term	0
lithium	1
treatment	0
and	0
the	0
kidney	0
.	0

Interim	0
report	0
on	0
fifty	0
patients	0
.	0

This	0
is	0
a	0
report	0
on	0
the	0
first	0
part	0
of	0
our	0
study	0
of	0
the	0
effects	0
of	0
long	0
-	0
term	0
lithium	1
treatment	0
on	0
the	0
kidney	0
.	0

Creatinine	1
clearance	0
,	0
maximum	0
urinary	0
osmolality	0
and	0
24	0
hour	0
urine	0
volume	0
have	0
been	0
tested	0
in	0
50	0
affectively	0
ill	0
patients	0
who	0
have	0
been	0
on	0
long	0
-	0
term	0
lithium	1
for	0
more	0
than	0
one	0
year	0
.	0

These	0
findings	0
have	0
been	0
compared	0
with	0
norms	0
and	0
with	0
values	0
of	0
the	0
same	0
tests	0
from	0
screening	0
prior	0
to	0
lithium	1
,	0
available	0
for	0
most	0
of	0
our	0
patients	0
.	0

No	0
evidence	0
was	0
found	0
for	0
any	0
reduction	0
of	0
glomerular	0
filtration	0
during	0
lithium	1
treatment	0
.	0

Low	0
clearance	0
values	0
found	0
in	0
several	0
patients	0
could	0
be	0
accounted	0
for	0
by	0
their	0
age	0
and	0
their	0
pre	0
-	0
lithium	1
values	0
.	0

Urinary	0
concentration	0
defect	0
appeared	0
frequent	0
but	0
the	0
extent	0
of	0
the	0
impairment	0
is	0
difficult	0
to	0
assess	0
because	0
of	0
the	0
uncertainty	0
about	0
the	0
norms	0
applicable	0
to	0
this	0
group	0
of	0
patients	0
.	0

The	0
concentration	0
defect	0
appeared	0
reversible	0
,	0
at	0
least	0
in	0
part	0
.	0

Polyuria	3
above	0
3	0
litres	0
/	0
24	0
hours	0
was	0
found	0
in	0
10	0
%	0
of	0
patients	0
.	0

An	0
attempt	0
is	0
made	0
to	0
draw	0
practical	0
conclusions	0
from	0
the	0
preliminary	0
findings	0
.	0

Nephrotoxicity	3
of	0
cyclosporin	1
A	2
and	0
FK506	1
:	0
inhibition	0
of	0
calcineurin	0
phosphatase	0
.	0

Cyclosporin	1
A	2
(	0
CsA	1
;	0
50	0
mg	0
/	0
kg	0
)	0
and	0
Fujimycine	1
(	0
FK506	1
;	0
5	0
mg	0
/	0
kg	0
)	0
,	0
but	0
not	0
the	0
related	0
macrolide	1
immunosuppressant	0
rapamycin	1
(	0
5	0
mg	0
/	0
kg	0
)	0
,	0
caused	0
a	0
reduction	0
of	0
glomerular	0
filtration	0
rate	0
,	0
degenerative	0
changes	0
of	0
proximal	0
tubular	0
epithelium	0
,	0
and	0
hypertrophy	3
of	0
the	0
juxtaglomerular	0
apparatus	0
in	0
male	0
Wistar	0
rats	0
when	0
given	0
for	0
10	0
days	0
.	0

The	0
molecular	0
mechanisms	0
of	0
CsA	1
and	0
FK506	1
toxicity	3
were	0
investigated	0
.	0

Cyclophilin	0
A	0
and	0
FK506	1
-	0
binding	0
protein	0
,	0
the	0
main	0
intracytoplasmic	0
receptors	0
for	0
CsA	1
and	0
FK506	1
,	0
respectively	0
,	0
were	0
each	0
detected	0
in	0
renal	0
tissue	0
extract	0
.	0

In	0
the	0
kidney	0
,	0
high	0
levels	0
of	0
immunoreactive	0
and	0
enzymatically	0
active	0
calcineurin	0
were	0
found	0
which	0
were	0
inhibited	0
by	0
the	0
immunosuppressants	0
CsA	1
and	0
FK506	1
,	0
but	0
not	0
by	0
rapamycin	1
.	0

Finally	0
,	0
specific	0
immunophilin	0
-	0
drug	0
-	0
calcineurin	0
complexes	0
formed	0
only	0
in	0
the	0
presence	0
of	0
CsA	1
and	0
FK506	1
,	0
but	0
not	0
rapamycin	1
.	0

These	0
results	0
suggest	0
that	0
the	0
nephrotoxic	3
effects	0
of	0
CsA	1
and	0
FK506	1
is	0
likely	0
mediated	0
through	0
binding	0
to	0
renal	0
immunophilin	0
and	0
inhibiting	0
calcineurin	0
phosphatase	0
.	0

Acute	3
renal	4
failure	4
in	0
high	0
dose	0
carboplatin	1
chemotherapy	0
.	0

Carboplatin	1
has	0
been	0
reported	0
to	0
cause	0
acute	3
renal	4
failure	4
when	0
administered	0
in	0
high	0
doses	0
to	0
adult	0
patients	0
.	0

We	0
report	0
a	0
4	0
1	0
/	0
2	0
-	0
year	0
-	0
old	0
girl	0
who	0
was	0
treated	0
with	0
high	0
-	0
dose	0
carboplatin	1
for	0
metastatic	0
parameningeal	0
embryonal	3
rhabdomyosarcoma	4
.	0

Acute	3
renal	4
failure	4
developed	0
followed	0
by	0
a	0
slow	0
partial	0
recovery	0
of	0
renal	0
function	0
.	0

Possible	0
contributing	0
factors	0
are	0
discussed	0
.	0

Clinical	0
evaluation	0
on	0
combined	0
administration	0
of	0
oral	0
prostacyclin	1
analogue	0
beraprost	1
and	0
phosphodiesterase	0
inhibitor	0
cilostazol	1
.	0

Among	0
various	0
oral	0
antiplatelets	0
,	0
a	0
combination	0
of	0
a	0
novel	0
prostacyclin	1
analogue	0
beraprost	1
(	0
BPT	1
)	0
and	0
a	0
potent	0
phosphodiesterase	0
inhibitor	0
cilostazol	1
(	0
CLZ	1
)	0
may	0
result	0
in	0
untoward	0
clinical	0
effects	0
due	0
to	0
possible	0
synergistic	0
elevation	0
of	0
intracellular	0
cAMP	1
(	0
cyclic	1
adenosine	2
3	2
'	2
,	2
5	2
'	2
-	2
monophosphate	2
)	0
.	0

Thereby	0
,	0
a	0
clinical	0
study	0
of	0
the	0
combined	0
administration	0
of	0
the	0
two	0
agents	0
was	0
attempted	0
.	0

Twelve	0
healthy	0
volunteers	0
were	0
assigned	0
to	0
take	0
BPT	1
/	0
CLZ	1
in	0
the	0
following	0
schedule	0
;	0
BPT	1
:	0
40	0
micrograms	0
at	0
day	0
1	0
and	0
120	0
micrograms	0
t	0
.	0
i	0
.	0
d	0
.	0
from	0
day	0
7	0
to	0
14	0
,	0
CLZ	1
:	0
200	0
mg	0
t	0
.	0
i	0
.	0
d	0
.	0
from	0
day	0
3	0
to	0
14	0
.	0

At	0
various	0
time	0
intervals	0
,	0
physical	0
examination	0
and	0
blood	0
collection	0
for	0
ex	0
vivo	0
platelet	3
aggregation	4
and	0
determination	0
of	0
intraplatelet	0
cAMP	1
were	0
performed	0
.	0

Throughout	0
the	0
observation	0
period	0
,	0
no	0
significant	0
alteration	0
in	0
vital	0
signs	0
was	0
observed	0
.	0

Seven	0
out	0
of	0
12	0
subjects	0
experienced	0
headache	3
of	0
a	0
short	0
duration	0
accompanying	0
facial	3
flush	4
in	0
one	0
and	0
nausea	3
in	0
one	0
,	0
especially	0
after	0
ingestion	0
of	0
CLZ	1
.	0

All	0
of	0
these	0
symptoms	0
,	0
probably	0
caused	0
by	0
the	0
vasodilating	0
effect	0
of	0
the	0
two	0
agents	0
,	0
were	0
of	0
mild	0
degree	0
and	0
no	0
special	0
treatment	0
was	0
required	0
.	0

Intraplatelet	0
cAMP	1
content	0
was	0
gradually	0
but	0
significantly	0
increased	0
to	0
9	0
.	0
84	0
+	0
/	0
-	0
4	0
.	0
59	0
pmol	0
per	0
10	0
(	0
9	0
)	0
platelets	0
at	0
day	0
14	0
in	0
comparison	0
with	0
the	0
initial	0
value	0
(	0
6	0
.	0
87	0
+	0
/	0
-	0
2	0
.	0
25	0
pmol	0
)	0
.	0

The	0
platelet	0
aggregability	0
was	0
significantly	0
suppressed	0
at	0
various	0
time	0
intervals	0
but	0
no	0
additive	0
or	0
synergistic	0
inhibitory	0
effect	0
by	0
the	0
combined	0
administration	0
was	0
noted	0
.	0

In	0
conclusion	0
,	0
the	0
combined	0
administration	0
of	0
BPT	1
/	0
CLZ	1
is	0
safe	0
at	0
doses	0
used	0
in	0
the	0
study	0
,	0
though	0
the	0
beneficial	0
clinical	0
effect	0
of	0
the	0
combined	0
administration	0
has	0
yet	0
to	0
be	0
elucidated	0
.	0

Pravastatin	1
-	0
associated	0
myopathy	3
.	0

Report	0
of	0
a	0
case	0
.	0

A	0
case	0
of	0
acute	0
inflammatory	3
myopathy	4
associated	0
with	0
the	0
use	0
of	0
pravastatin	1
,	0
a	0
new	0
hydrophilic	0
3	0
-	0
hydroxy	0
-	0
3	0
methylglutaril	0
coenzyme	0
A	0
reductase	0
inhibitor	0
,	0
is	0
reported	0
.	0

The	0
patient	0
,	0
a	0
69	0
-	0
year	0
-	0
old	0
man	0
was	0
affected	0
by	0
non	3
-	4
insulin	4
-	4
dependent	4
diabetes	4
mellitus	4
and	0
hypertension	3
.	0

He	0
assumed	0
pravastatin	1
(	0
20	0
mg	0
/	0
day	0
)	0
because	0
of	0
hypercholesterolemia	3
.	0

He	0
was	0
admitted	0
with	0
acute	0
myopathy	3
of	0
the	0
lower	0
limbs	0
which	0
resolved	0
in	0
a	0
few	0
days	0
after	0
pravastatin	1
discontinuation	0
.	0

A	0
previously	0
unknown	0
hypothyroidism	3
,	0
probably	0
due	0
to	0
chronic	0
autoimmune	3
thyroiditis	4
,	0
was	0
evidenced	0
.	0

Muscle	0
biopsy	0
(	0
left	0
gastrocnemius	0
)	0
revealed	0
a	0
perimysial	0
and	0
endomysial	0
inflammatory	0
infiltrate	0
with	0
a	0
prevalence	0
of	0
CD4	0
+	0
lymphocytes	0
.	0

While	0
lovastatin	1
and	0
simvastatin	1
have	0
been	0
associated	0
with	0
toxic	0
myopathy	3
,	0
pravastatin	1
-	0
associated	0
myopathy	3
could	0
represent	0
a	0
distinct	0
,	0
inflammatory	0
entity	0
.	0

Reversal	0
of	0
ammonia	1
coma	3
in	0
rats	0
by	0
L	1
-	2
dopa	2
:	0
a	0
peripheral	0
effect	0
.	0

Ammonia	1
coma	3
was	0
produced	0
in	0
rats	0
within	0
10	0
to	0
15	0
minutes	0
of	0
an	0
intraperitonealinjection	0
of	0
1	0
.	0
7	0
mmol	0
NH4CL	1
.	0

This	0
coma	3
was	0
prevented	0
with	0
1	0
.	0
68	0
mmol	0
L	1
-	2
dopa	2
given	0
by	0
gastric	0
intubation	0
15	0
minutes	0
before	0
the	0
ammonium	1
salt	2
injection	0
.	0

The	0
effect	0
of	0
L	1
-	2
dopa	2
was	0
correlated	0
with	0
a	0
decrease	0
in	0
blood	0
and	0
brain	0
ammonia	1
,	0
an	0
increase	0
in	0
brain	0
dopamine	1
,	0
and	0
an	0
increase	0
in	0
renal	0
excretion	0
of	0
ammonia	1
and	0
urea	1
.	0

Intraventricular	0
infusion	0
of	0
dopamine	1
sufficient	0
to	0
raise	0
the	0
brain	0
dopamine	1
to	0
the	0
same	0
extent	0
did	0
not	0
prevent	0
the	0
ammonia	1
coma	3
nor	0
affect	0
the	0
blood	0
and	0
brain	0
ammonia	1
concentrations	0
.	0

Bilateral	0
nephrectomy	0
eliminated	0
the	0
beneficial	0
effect	0
of	0
L	1
-	2
dopa	2
on	0
blood	0
and	0
brain	0
ammonia	1
and	0
the	0
ammonia	1
coma	3
was	0
not	0
prevented	0
.	0

Thus	0
,	0
the	0
reduction	0
in	0
blood	0
and	0
brain	0
ammonia	1
and	0
the	0
prevention	0
of	0
ammonia	1
coma	3
after	0
L	1
-	2
dopa	2
,	0
can	0
be	0
accounted	0
for	0
by	0
the	0
peripheral	0
effect	0
of	0
dopamine	1
on	0
renal	0
function	0
rather	0
than	0
its	0
central	0
action	0
.	0

These	0
results	0
provide	0
a	0
reasonable	0
explanation	0
for	0
the	0
beneficial	0
effects	0
observed	0
in	0
some	0
encephalopathic	3
patients	0
receiving	0
L	1
-	2
dopa	2
.	0

Etoposide	1
-	0
related	0
myocardial	3
infarction	4
.	0

The	0
occurrence	0
of	0
a	0
myocardial	3
infarction	4
is	0
reported	0
after	0
chemotherapy	0
containing	0
etoposide	1
,	0
in	0
a	0
man	0
with	0
no	0
risk	0
factors	0
for	0
coronary	3
heart	4
disease	4
.	0

Possible	0
causal	0
mechanisms	0
are	0
discussed	0
.	0

Halogenated	0
anesthetics	0
form	0
liver	0
adducts	0
and	0
antigens	0
that	0
cross	0
-	0
react	0
with	0
halothane	1
-	0
induced	0
antibodies	0
.	0

Two	0
halogenated	0
anesthetics	0
,	0
enflurane	1
and	0
isoflurane	1
,	0
have	0
been	0
associated	0
with	0
an	0
allergic	0
-	0
type	0
hepatic	3
injury	4
both	0
alone	0
and	0
following	0
previous	0
exposure	0
to	0
halothane	1
.	0

Halothane	1
hepatitis	3
appears	0
to	0
involve	0
an	0
aberrant	0
immune	0
response	0
.	0

An	0
antibody	0
response	0
to	0
a	0
protein	0
-	0
bound	0
biotransformation	0
product	0
(	0
trifluoroacetyl	1
adduct	0
)	0
has	0
been	0
detected	0
on	0
halothane	1
hepatitis	3
patients	0
.	0

This	0
study	0
was	0
performed	0
to	0
determine	0
cross	0
-	0
reactivity	0
between	0
enflurane	1
and	0
isoflurane	1
with	0
the	0
hypersensitivity	3
induced	0
by	0
halothane	1
.	0

The	0
subcellular	0
and	0
lobular	0
production	0
of	0
hepatic	0
neoantigens	0
recognized	0
by	0
halothane	1
-	0
induced	0
antibodies	0
following	0
enflurane	1
and	0
isoflurane	1
,	0
and	0
the	0
biochemical	0
nature	0
of	0
these	0
neoantigens	0
was	0
investigated	0
in	0
two	0
animal	0
models	0
.	0

Enflurane	1
administration	0
resulted	0
in	0
neoantigens	0
detected	0
in	0
both	0
the	0
microsomal	0
and	0
cytosolic	0
fraction	0
of	0
liver	0
homogenates	0
and	0
in	0
the	0
centrilobular	0
region	0
of	0
the	0
liver	0
.	0

In	0
the	0
same	0
liver	0
,	0
biochemical	0
analysis	0
detected	0
fluorinated	0
liver	0
adducts	0
that	0
were	0
up	0
to	0
20	0
-	0
fold	0
greater	0
in	0
guinea	0
pigs	0
than	0
in	0
rats	0
.	0

This	0
supports	0
and	0
extends	0
previous	0
evidence	0
for	0
a	0
mechanism	0
by	0
which	0
enflurane	1
and	0
/	0
or	0
isoflurane	1
could	0
produce	0
a	0
hypersensitivity	3
condition	0
similar	0
to	0
that	0
of	0
halothane	1
hepatitis	3
either	0
alone	0
or	0
subsequent	0
to	0
halothane	1
administration	0
.	0

The	0
guinea	0
pig	0
would	0
appear	0
to	0
be	0
a	0
useful	0
model	0
for	0
further	0
investigations	0
of	0
the	0
immunological	0
response	0
to	0
these	0
antigens	0
.	0

Cholinergic	0
toxicity	3
resulting	0
from	0
ocular	0
instillation	0
of	0
echothiophate	1
iodide	2
eye	0
drops	0
.	0

A	0
patient	0
developed	0
a	0
severe	0
cholinergic	0
syndrome	0
from	0
the	0
use	0
of	0
echothiophate	1
iodide	2
ophthalmic	0
drops	0
,	0
presented	0
with	0
profound	0
muscle	3
weakness	4
and	0
was	0
initially	0
given	0
the	0
diagnosis	0
of	0
myasthenia	3
gravis	4
.	0

Red	0
blood	0
cell	0
and	0
serum	0
cholinesterase	0
levels	0
were	0
severely	0
depressed	0
and	0
symptoms	0
resolved	0
spontaneously	0
following	0
discontinuation	0
of	0
the	0
eye	0
drops	0
.	0

Seizure	3
after	0
flumazenil	1
administration	0
in	0
a	0
pediatric	0
patient	0
.	0

Flumazenil	1
is	0
a	0
benzodiazepine	1
receptor	0
antagonist	0
used	0
to	0
reverse	0
sedation	0
and	0
respiratory	3
depression	4
induced	0
by	0
benzodiazepines	1
.	0

Seizures	3
and	0
cardiac	3
arrhythmias	4
have	0
complicated	0
its	0
use	0
in	0
adult	0
patients	0
.	0

0verdose	3
patients	0
who	0
have	0
coingested	0
tricyclic	0
antidepressants	0
have	0
a	0
higher	0
risk	0
of	0
these	0
complications	0
.	0

Little	0
information	0
exists	0
concerning	0
adverse	0
effects	0
of	0
flumazenil	1
in	0
children	0
.	0

We	0
report	0
the	0
occurrence	0
of	0
a	0
generalized	0
tonic	3
-	4
clonic	4
seizure	4
in	0
a	0
pediatric	0
patient	0
following	0
the	0
administration	0
of	0
flumazenil	1
.	0

Phase	0
I	0
trial	0
of	0
13	1
-	2
cis	2
-	2
retinoic	2
acid	2
in	0
children	0
with	0
neuroblastoma	3
following	0
bone	0
marrow	0
transplantation	0
.	0

PURP0SE	0
:	0
Treatment	0
of	0
neuroblastoma	3
cell	0
lines	0
with	0
13	1
-	2
cis	2
-	2
retinoic	2
acid	2
(	0
cis	1
-	2
RA	2
)	0
can	0
cause	0
sustained	0
inhibition	0
of	0
proliferation	0
.	0

Since	0
cis	1
-	2
RA	2
has	0
demonstrated	0
clinical	0
responses	0
in	0
neuroblastoma	3
patients	0
,	0
it	0
may	0
be	0
effective	0
in	0
preventing	0
relapse	0
after	0
cytotoxic	0
therapy	0
.	0

This	0
phase	0
I	0
trial	0
was	0
designed	0
to	0
determine	0
the	0
maximal	0
-	0
tolerated	0
dosage	0
(	0
MTD	0
)	0
,	0
toxicities	3
,	0
and	0
pharmacokinetics	0
of	0
cis	1
-	2
RA	2
administered	0
on	0
an	0
intermittent	0
schedule	0
in	0
children	0
with	0
neuroblastoma	3
following	0
bone	0
marrow	0
transplantation	0
(	0
BMT	0
)	0
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
Fifty	0
-	0
one	0
assessable	0
patients	0
,	0
2	0
to	0
12	0
years	0
of	0
age	0
,	0
were	0
treated	0
with	0
oral	0
cis	1
-	2
RA	2
administered	0
in	0
two	0
equally	0
divided	0
doses	0
daily	0
for	0
2	0
weeks	0
,	0
followed	0
by	0
a	0
2	0
-	0
week	0
rest	0
period	0
,	0
for	0
up	0
to	0
12	0
courses	0
.	0

The	0
dose	0
was	0
escalated	0
from	0
100	0
to	0
200	0
mg	0
/	0
m2	0
/	0
d	0
until	0
dose	0
-	0
limiting	0
toxicity	3
(	0
DLT	0
)	0
was	0
observed	0
.	0

A	0
single	0
intrapatient	0
dose	0
escalation	0
was	0
permitted	0
.	0

RESULTS	0
:	0
The	0
MTD	0
of	0
cis	1
-	2
RA	2
was	0
160	0
mg	0
/	0
m2	0
/	0
d	0
.	0

Dose	0
-	0
limiting	0
toxicities	3
in	0
six	0
of	0
nine	0
patients	0
at	0
200	0
mg	0
/	0
m2	0
/	0
d	0
included	0
hypercalcemia	3
(	0
n	0
=	0
3	0
)	0
,	0
rash	3
(	0
n	0
=	0
2	0
)	0
,	0
and	0
anemia	3
/	0
thrombocytopenia	3
/	0
emesis	3
/	0
rash	3
(	0
n	0
=	0
1	0
)	0
.	0

All	0
toxicities	3
resolved	0
after	0
cis	1
-	2
RA	2
was	0
discontinued	0
.	0

Three	0
complete	0
responses	0
were	0
observed	0
in	0
marrow	0
metastases	3
.	0

Serum	0
levels	0
of	0
7	0
.	0
4	0
+	0
/	0
-	0
3	0
.	0
0	0
mumol	0
/	0
L	0
(	0
peak	0
)	0
and	0
4	0
.	0
0	0
+	0
/	0
-	0
2	0
.	0
8	0
mumol	0
/	0
L	0
(	0
trough	0
)	0
at	0
the	0
MTD	0
were	0
maintained	0
during	0
14	0
days	0
of	0
therapy	0
.	0

The	0
DLT	0
correlated	0
with	0
serum	0
levels	0
>	0
or	0
=	0
10	0
mumol	0
/	0
L	0
.	0

C0NCLUSI0N	0
:	0
The	0
MTD	0
of	0
cis	1
-	2
RA	2
given	0
on	0
this	0
intermittent	0
schedule	0
was	0
160	0
mg	0
/	0
m2	0
/	0
d	0
.	0

Serum	0
levels	0
known	0
to	0
be	0
effective	0
against	0
neuroblastoma	3
in	0
vitro	0
were	0
achieved	0
at	0
this	0
dose	0
.	0

The	0
DLT	0
included	0
hypercalcemia	3
,	0
and	0
may	0
be	0
predicted	0
by	0
serum	0
cis	1
-	2
RA	2
levels	0
.	0

Monitoring	0
of	0
serum	0
calcium	1
and	0
cis	1
-	2
RA	2
levels	0
is	0
indicated	0
in	0
future	0
trials	0
.	0

Time	0
dependence	0
of	0
plasma	0
malondialdehyde	1
,	0
oxypurines	1
,	0
and	0
nucleosides	1
during	0
incomplete	0
cerebral	3
ischemia	4
in	0
the	0
rat	0
.	0

Incomplete	0
cerebral	3
ischemia	4
(	0
30	0
min	0
)	0
was	0
induced	0
in	0
the	0
rat	0
by	0
bilaterally	0
clamping	0
the	0
common	0
carotid	0
arteries	0
.	0

Peripheral	0
venous	0
blood	0
samples	0
were	0
withdrawn	0
from	0
the	0
femoral	0
vein	0
four	0
times	0
(	0
once	0
every	0
5	0
min	0
)	0
before	0
ischemia	3
(	0
0	0
time	0
)	0
and	0
5	0
,	0
15	0
,	0
and	0
30	0
min	0
after	0
ischemia	3
.	0

Plasma	0
extracts	0
were	0
analyzed	0
by	0
a	0
highly	0
sensitive	0
high	0
-	0
performance	0
liquid	0
chromatographic	0
method	0
for	0
the	0
direct	0
determination	0
of	0
malondialdehyde	1
,	0
oxypurines	1
,	0
and	0
nucleosides	1
.	0

During	0
ischemia	3
,	0
a	0
time	0
-	0
dependent	0
increase	0
of	0
plasma	0
oxypurines	1
and	0
nucleosides	1
was	0
observed	0
.	0

Plasma	0
malondialdehyde	1
,	0
which	0
was	0
present	0
in	0
minimal	0
amount	0
at	0
zero	0
time	0
(	0
0	0
.	0
058	0
mumol	0
/	0
liter	0
plasma	0
;	0
SD	0
0	0
.	0
015	0
)	0
,	0
increased	0
after	0
5	0
min	0
of	0
ischemia	3
,	0
resulting	0
in	0
a	0
fivefold	0
increase	0
after	0
30	0
min	0
of	0
carotid	0
occlusion	0
(	0
0	0
.	0
298	0
mumol	0
/	0
liter	0
plasma	0
;	0
SD	0
0	0
.	0
078	0
)	0
.	0

Increased	0
plasma	0
malondialdehyde	1
was	0
also	0
recorded	0
in	0
two	0
other	0
groups	0
of	0
animals	0
subjected	0
to	0
the	0
same	0
experimental	0
model	0
,	0
one	0
receiving	0
20	0
mg	0
/	0
kg	0
b	0
.	0
w	0
.	0
of	0
the	0
cyclooxygenase	0
inhibitor	0
acetylsalicylate	1
intravenously	0
immediately	0
before	0
ischemia	3
,	0
the	0
other	0
receiving	0
650	0
micrograms	0
/	0
kg	0
b	0
.	0
w	0
.	0
of	0
the	0
hypotensive	3
drug	0
nitroprusside	1
at	0
a	0
flow	0
rate	0
of	0
103	0
microliters	0
/	0
min	0
intravenously	0
during	0
ischemia	3
,	0
although	0
in	0
this	0
latter	0
group	0
malondialdehyde	1
was	0
significantly	0
higher	0
.	0

The	0
present	0
data	0
indicate	0
that	0
the	0
determination	0
of	0
malondialdehyde	1
,	0
oxypurines	1
,	0
and	0
nucleosides	1
in	0
peripheral	0
blood	0
,	0
may	0
be	0
used	0
to	0
monitor	0
the	0
metabolic	0
alterations	0
of	0
tissues	0
occurring	0
during	0
ischemic	3
phenomena	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Acute	0
renal	3
toxicity	4
of	0
doxorubicin	1
(	0
adriamycin	1
)	0
-	0
loaded	0
cyanoacrylate	1
nanoparticles	0
.	0

Acute	0
doxorubicin	1
-	0
loaded	0
nanoparticle	0
(	0
DXNP	0
)	0
renal	3
toxicity	4
was	0
explored	0
in	0
both	0
normal	0
rats	0
and	0
rats	0
with	0
experimental	0
glomerulonephritis	3
.	0

In	0
normal	0
rats	0
,	0
2	0
/	0
6	0
rats	0
given	0
free	0
doxorubicin	1
(	0
DX	1
)	0
(	0
5	0
mg	0
/	0
kg	0
)	0
died	0
within	0
one	0
week	0
,	0
whereas	0
all	0
control	0
animals	0
and	0
all	0
rats	0
having	0
received	0
free	0
NP	0
or	0
DXNP	0
survived	0
.	0

A	0
3	0
times	0
higher	0
proteinuria	3
appeared	0
in	0
animals	0
treated	0
with	0
DXNP	0
than	0
in	0
those	0
treated	0
with	0
DX	1
.	0

Free	0
NP	0
did	0
not	0
provoke	0
any	0
proteinuria	3
.	0

Two	0
hr	0
post	0
-	0
injection	0
,	0
DXNP	0
was	0
2	0
.	0
7	0
times	0
more	0
concentrated	0
in	0
kidneys	0
than	0
free	0
DX	1
(	0
p	0
<	0
0	0
.	0
025	0
)	0
.	0

In	0
rats	0
with	0
immune	0
experimental	0
glomerulonephritis	3
,	0
5	0
/	0
6	0
rats	0
given	0
DX	1
died	0
within	0
7	0
days	0
,	0
in	0
contrast	0
to	0
animals	0
treated	0
by	0
DXNP	0
,	0
NP	0
,	0
or	0
untreated	0
,	0
which	0
all	0
survived	0
.	0

Proteinuria	3
appeared	0
in	0
all	0
series	0
,	0
but	0
was	0
2	0
-	0
5	0
times	0
more	0
intense	0
(	0
p	0
>	0
0	0
.	0
001	0
)	0
and	0
prolonged	0
after	0
doxorubicin	1
treatment	0
(	0
400	0
-	0
700	0
mg	0
/	0
day	0
)	0
,	0
without	0
significant	0
difference	0
between	0
DXNP	0
and	0
DX	1
.	0

Rats	0
treated	0
by	0
unloaded	0
NP	0
behaved	0
as	0
controls	0
.	0

These	0
results	0
demonstrate	0
that	0
,	0
in	0
these	0
experimental	0
conditions	0
,	0
DXNP	0
killed	0
less	0
animals	0
than	0
free	0
DX	1
,	0
despite	0
of	0
an	0
enhanced	0
renal	3
toxicity	4
of	0
the	0
former	0
.	0

Both	0
effects	0
(	0
better	0
survival	0
and	0
nephrosis	3
)	0
are	0
most	0
probably	0
related	0
to	0
an	0
enhanced	0
capture	0
of	0
DXNP	0
by	0
cells	0
of	0
the	0
mononuclear	0
phagocyte	0
system	0
,	0
including	0
mesangial	0
cells	0
.	0

Prostaglandin	1
E2	2
-	0
induced	0
bladder	3
hyperactivity	4
in	0
normal	0
,	0
conscious	0
rats	0
:	0
involvement	0
of	0
tachykinins	1
?	0

In	0
normal	0
conscious	0
rats	0
investigated	0
by	0
continuous	0
cystometry	0
,	0
intravesically	0
instilled	0
prostaglandin	1
(	2
PG	2
)	2
E2	2
facilitated	0
micturition	0
and	0
increased	0
basal	0
intravesical	0
pressure	0
.	0

The	0
effect	0
was	0
attenuated	0
by	0
both	0
the	0
NK1	0
receptor	0
selective	0
antagonist	0
RP	1
67	2
,	2
580	2
and	0
the	0
NK2	0
receptor	0
selective	0
antagonist	0
SR	1
48	2
,	2
968	2
,	0
given	0
intra	0
-	0
arterially	0
,	0
suggesting	0
that	0
it	0
was	0
mediated	0
by	0
stimulation	0
of	0
both	0
NK1	0
and	0
NK2	0
receptors	0
.	0

Intra	0
-	0
arterially	0
given	0
PGE2	1
produced	0
a	0
distinct	0
increase	0
in	0
bladder	0
pressure	0
before	0
initiating	0
a	0
micturition	0
reflex	0
,	0
indicating	0
that	0
the	0
PG	1
had	0
a	0
direct	0
contractant	0
effect	0
on	0
the	0
detrusor	0
smooth	0
muscle	0
.	0

The	0
effect	0
of	0
intra	0
-	0
arterial	0
PGE2	1
could	0
not	0
be	0
blocked	0
by	0
intra	0
-	0
arterial	0
RP	1
67	2
,	2
580	2
or	0
SR	1
48	2
,	2
968	2
,	0
which	0
opens	0
the	0
possibility	0
that	0
the	0
micturition	0
reflex	0
elicited	0
by	0
intra	0
-	0
arterial	0
PGE2	1
was	0
mediated	0
by	0
pathways	0
other	0
than	0
the	0
reflex	0
initiated	0
when	0
the	0
PG	1
was	0
given	0
intravesically	0
.	0

The	0
present	0
results	0
thus	0
suggest	0
that	0
intra	0
-	0
arterial	0
PGE2	1
,	0
given	0
near	0
the	0
bladder	0
,	0
may	0
initiate	0
micturition	0
in	0
the	0
normal	0
rat	0
chiefly	0
by	0
directly	0
contracting	0
the	0
smooth	0
muscle	0
of	0
the	0
detrusor	0
.	0

However	0
,	0
when	0
given	0
intravesically	0
,	0
PGE2	1
may	0
stimulate	0
micturition	0
by	0
releasing	0
tachykinins	1
from	0
nerves	0
in	0
and	0
/	0
or	0
immediately	0
below	0
the	0
urothelium	0
.	0

These	0
tachykinins	1
,	0
in	0
turn	0
,	0
initiate	0
a	0
micturition	0
reflex	0
by	0
stimulating	0
NK1	0
and	0
NK2	0
receptors	0
.	0

Prostanoids	1
may	0
,	0
via	0
release	0
of	0
tachykinins	1
,	0
contribute	0
to	0
both	0
urge	0
and	0
bladder	3
hyperactivity	4
seen	0
in	0
inflammatory	0
conditions	0
of	0
the	0
lower	0
urinary	0
tract	0
.	0

Refractory	0
cardiogenic	3
shock	4
and	0
complete	0
heart	3
block	4
after	0
verapamil	1
SR	0
and	0
metoprolol	1
treatment	0
.	0

A	0
case	0
report	0
.	0

A	0
seventy	0
-	0
eight	0
-	0
year	0
-	0
old	0
woman	0
presented	0
with	0
complete	0
heart	3
block	4
and	0
refractory	0
hypotension	3
two	0
days	0
after	0
a	0
therapeutic	0
dose	0
of	0
sustained	0
-	0
release	0
verapamil	1
with	0
concomitant	0
use	0
of	0
metoprolol	1
.	0

The	0
patient	0
continued	0
to	0
remain	0
hypotensive	3
with	0
complete	0
heart	3
block	4
,	0
even	0
with	0
multiple	0
uses	0
of	0
intravenous	0
atropine	1
as	0
well	0
as	0
high	0
doses	0
of	0
pressor	0
agents	0
such	0
as	0
dopamine	1
and	0
dobutamine	1
.	0

However	0
,	0
shortly	0
after	0
the	0
use	0
of	0
intravenous	0
calcium	1
chloride	2
,	0
the	0
refractory	0
hypotension	3
and	0
complete	0
heart	3
block	4
resolved	0
.	0

Protective	0
effect	0
of	0
misoprostol	1
on	0
indomethacin	1
induced	0
renal	3
dysfunction	4
in	0
elderly	0
patients	0
.	0

0BJECTIVE	0
:	0
To	0
evaluate	0
the	0
possible	0
protective	0
effects	0
of	0
misoprostol	1
on	0
renal	0
function	0
in	0
hospitalized	0
elderly	0
patients	0
treated	0
with	0
indomethacin	1
.	0

METH0DS	0
:	0
Forty	0
-	0
five	0
hospitalized	0
elderly	0
patients	0
(	0
>	0
65	0
years	0
old	0
)	0
who	0
required	0
therapy	0
with	0
nonsteroidal	0
antiinflammatory	0
drugs	0
(	0
NSAID	0
)	0
were	0
randomly	0
assigned	0
to	0
receive	0
either	0
indomethacin	1
,	0
150	0
mg	0
/	0
day	0
(	0
Group	0
A	0
)	0
,	0
or	0
indomethacin	1
150	0
mg	0
/	0
day	0
plus	0
misoprostol	1
at	0
0	0
.	0
6	0
mg	0
/	0
day	0
(	0
Group	0
B	0
)	0
.	0

Laboratory	0
variables	0
of	0
renal	0
function	0
[	0
serum	0
creatinine	1
,	0
blood	1
urea	2
nitrogen	2
(	0
BUN	1
)	0
and	0
electrolytes	0
]	0
were	0
evaluated	0
before	0
initiation	0
of	0
therapy	0
and	0
every	0
2	0
days	0
,	0
until	0
termination	0
of	0
the	0
study	0
(	0
a	0
period	0
of	0
at	0
least	0
6	0
days	0
)	0
.	0

Response	0
to	0
treatment	0
was	0
estimated	0
by	0
the	0
visual	0
analog	0
scale	0
for	0
severity	0
of	0
pain	3
.	0

RESULTS	0
:	0
Forty	0
-	0
two	0
patients	0
completed	0
the	0
study	0
,	0
22	0
in	0
Group	0
A	0
and	0
20	0
in	0
Group	0
B	0
.	0

BUN	1
and	0
creatinine	1
increased	0
by	0
>	0
50	0
%	0
of	0
baseline	0
levels	0
in	0
54	0
and	0
45	0
%	0
of	0
Group	0
A	0
patients	0
,	0
respectively	0
,	0
compared	0
to	0
only	0
20	0
and	0
10	0
%	0
of	0
Group	0
B	0
patients	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

Potassium	1
(	0
K	1
)	0
increment	0
of	0
0	0
.	0
6	0
mEq	0
/	0
l	0
or	0
more	0
was	0
observed	0
in	0
50	0
%	0
of	0
Group	0
A	0
,	0
but	0
in	0
only	0
15	0
%	0
of	0
Group	0
B	0
patients	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

The	0
mean	0
increments	0
in	0
BUN	1
,	0
creatinine	1
,	0
and	0
K	1
were	0
reduced	0
by	0
63	0
,	0
80	0
,	0
and	0
42	0
%	0
,	0
respectively	0
,	0
in	0
Group	0
B	0
patients	0
compared	0
to	0
Group	0
A	0
.	0
Response	0
to	0
treatment	0
did	0
not	0
differ	0
significantly	0
between	0
the	0
2	0
groups	0
.	0

C0NCLUSI0N	0
:	0
Hospitalized	0
elderly	0
patients	0
are	0
at	0
risk	0
for	0
developing	0
indomethacin	1
related	0
renal	3
dysfunction	4
.	0

Addition	0
of	0
misoprostol	1
can	0
minimize	0
this	0
renal	3
impairment	4
without	0
affecting	0
pain	3
control	0
.	0

Cognitive	3
deterioration	4
from	0
long	0
-	0
term	0
abuse	0
of	0
dextromethorphan	1
:	0
a	0
case	0
report	0
.	0

Dextromethorphan	1
(	0
DM	1
)	0
,	0
the	0
dextrorotatory	0
isomer	0
of	0
3	1
-	2
hydroxy	2
-	2
N	2
-	2
methylmorphinan	2
,	0
is	0
the	0
main	0
ingredient	0
in	0
a	0
number	0
of	0
widely	0
available	0
,	0
over	0
-	0
the	0
-	0
counter	0
antitussives	0
.	0

Initial	0
studies	0
(	0
Bornstein	0
1968	0
)	0
showed	0
that	0
it	0
possessed	0
no	0
respiratory	0
suppressant	0
effects	0
and	0
no	0
addiction	0
liability	0
.	0

Subsequently	0
,	0
however	0
,	0
several	0
articles	0
reporting	0
abuse	0
of	0
this	0
drug	0
have	0
appeared	0
in	0
the	0
literature	0
.	0

The	0
drug	0
is	0
known	0
to	0
cause	0
a	0
variety	0
of	0
acute	0
toxic	0
effects	0
,	0
ranging	0
from	0
nausea	3
,	0
restlessness	3
,	0
insomnia	3
,	0
ataxia	3
,	0
slurred	0
speech	0
and	0
nystagmus	3
to	0
mood	0
changes	0
,	0
perceptual	0
alterations	0
,	0
inattention	0
,	0
disorientation	0
and	0
aggressive	3
behavior	4
(	0
Rammer	0
et	0
al	0
1988	0
;	0
Katona	0
and	0
Watson	0
1986	0
;	0
Isbell	0
and	0
Fraser	0
1953	0
;	0
Devlin	0
et	0
al	0
1985	0
;	0
McCarthy	0
1971	0
;	0
Dodds	0
and	0
Revai	0
1967	0
;	0
Degkwitz	0
1964	0
;	0
Hildebrand	0
et	0
al	0
1989	0
)	0
.	0

There	0
have	0
also	0
been	0
two	0
reported	0
fatalities	0
from	0
DM	1
overdoses	0
(	0
Fleming	0
1986	0
)	0
.	0

However	0
,	0
there	0
are	0
no	0
reports	0
describing	0
the	0
effects	0
of	0
chronic	0
abuse	0
.	0

This	0
report	0
describes	0
a	0
case	0
of	0
cognitive	3
deterioration	4
resulting	0
from	0
prolonged	0
use	0
of	0
DM	1
.	0

Effects	0
of	0
ouabain	1
on	0
myocardial	0
oxygen	1
supply	0
and	0
demand	0
in	0
patients	0
with	0
chronic	0
coronary	3
artery	4
disease	4
.	0

A	0
hemodynamic	0
,	0
volumetric	0
,	0
and	0
metabolic	0
study	0
in	0
patients	0
without	0
heart	3
failure	4
.	0

The	0
effects	0
of	0
digitalis	1
glycosides	2
on	0
myocardial	0
oxygen	1
supply	0
and	0
demand	0
are	0
of	0
particular	0
interest	0
in	0
the	0
presence	0
of	0
obstructive	0
coronary	3
artery	4
disease	4
,	0
but	0
have	0
not	0
been	0
measured	0
previously	0
in	0
man	0
.	0

We	0
assessed	0
the	0
effects	0
of	0
ouabain	1
(	0
0	0
.	0
015	0
mg	0
/	0
kg	0
body	0
weight	0
)	0
on	0
hemodynamic	0
,	0
volumetric	0
,	0
and	0
metabolic	0
parameters	0
in	0
11	0
patients	0
with	0
severe	0
chronic	0
coronary	3
artery	4
disease	4
without	0
clinical	0
congestive	3
heart	4
failure	4
.	0

Because	0
the	0
protocol	0
was	0
long	0
and	0
involved	0
interventions	0
which	0
might	0
affect	0
the	0
determinations	0
,	0
we	0
also	0
studied	0
in	0
nine	0
patients	0
using	0
an	0
identical	0
protocol	0
except	0
that	0
ouabain	1
administration	0
was	0
omitted	0
.	0

Left	0
ventricular	0
end	0
-	0
diastolic	0
pressure	0
and	0
left	0
ventricular	0
end	0
-	0
diastolic	0
volume	0
fell	0
in	0
each	0
patient	0
given	0
ouabain	1
,	0
even	0
though	0
they	0
were	0
initially	0
elevated	0
in	0
only	0
two	0
patients	0
.	0

Left	0
ventricular	0
end	0
-	0
diastolic	0
pressure	0
fell	0
from	0
11	0
.	0
5	0
+	0
/	0
-	0
1	0
.	0
4	0
(	0
mean	0
+	0
/	0
-	0
SE	0
)	0
to	0
5	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
9	0
mm	0
Hg	0
(	0
P	0
less	0
than	0
0	0
.	0
001	0
)	0
and	0
left	0
ventricular	0
end	0
-	0
diastolic	0
volume	0
fell	0
from	0
100	0
+	0
/	0
-	0
17	0
to	0
82	0
+	0
/	0
-	0
12	0
ml	0
/	0
m2	0
(	0
P	0
less	0
than	0
0	0
.	0
01	0
)	0
1	0
h	0
after	0
ouabain	1
infusion	0
was	0
completed	0
.	0

The	0
maximum	0
velocity	0
of	0
contractile	0
element	0
shortening	0
increased	0
from	0
1	0
.	0
68	0
+	0
/	0
-	0
0	0
.	0
11	0
ml	0
/	0
s	0
to	0
2	0
.	0
18	0
+	0
/	0
-	0
0	0
.	0
21	0
muscle	0
-	0
lengths	0
/	0
s	0
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
and	0
is	0
consistent	0
with	0
an	0
increase	0
in	0
contractility	0
.	0

No	0
significant	0
change	0
in	0
these	0
parameters	0
occurred	0
in	0
the	0
control	0
patients	0
.	0

No	0
significant	0
change	0
in	0
myocardial	0
oxygen	1
consumption	0
occurred	0
after	0
ouabain	1
administration	0
but	0
this	0
may	0
be	0
related	0
to	0
a	0
greater	0
decrease	0
in	0
mean	0
arterial	0
pressure	0
in	0
the	0
ouabain	1
patients	0
than	0
in	0
the	0
control	0
patients	0
.	0

We	0
conclude	0
that	0
in	0
patients	0
with	0
chronic	0
coronary	3
artery	4
disease	4
who	0
are	0
not	0
in	0
clinical	0
congestive	3
heart	4
failure	4
left	3
ventricular	4
end	4
-	4
diastolic	4
volume	4
falls	4
after	0
ouabain	1
administration	0
even	0
when	0
it	0
is	0
initially	0
normal	0
.	0

Though	0
this	0
fall	0
would	0
be	0
associated	0
with	0
a	0
decrease	0
in	0
wall	0
tension	0
,	0
and	0
,	0
therefore	0
,	0
of	0
myocardial	0
oxygen	1
consumption	0
,	0
it	0
may	0
not	0
be	0
of	0
sufficient	0
magnitude	0
to	0
prevent	0
a	0
net	0
increase	0
in	0
myocardial	0
oxygen	1
consumption	0
.	0

Nevertheless	0
,	0
compensatory	0
mechanisms	0
prevent	0
a	0
deterioration	0
of	0
resting	0
myocardial	0
metabolism	0
.	0

Dexamethasone	1
-	0
induced	0
ocular	3
hypertension	4
in	0
perfusion	0
-	0
cultured	0
human	0
eyes	0
.	0

PURP0SE	0
:	0
Glucocorticoid	0
administration	0
can	0
lead	0
to	0
the	0
development	0
of	0
ocular	3
hypertension	4
and	0
corticosteroid	3
glaucoma	4
in	0
a	0
subset	0
of	0
the	0
population	0
through	0
a	0
decrease	0
in	0
the	0
aqueous	0
humor	0
outflow	0
facility	0
.	0

The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
determine	0
whether	0
glucocorticoid	0
treatment	0
can	0
directly	0
affect	0
the	0
outflow	0
facility	0
of	0
isolated	0
,	0
perfusion	0
-	0
cultured	0
human	0
eyes	0
.	0

METH0DS	0
:	0
The	0
anterior	0
segments	0
of	0
human	0
donor	0
eyes	0
from	0
regional	0
eye	0
banks	0
were	0
placed	0
in	0
a	0
constant	0
flow	0
,	0
variable	0
pressure	0
perfusion	0
culture	0
system	0
.	0

Paired	0
eyes	0
were	0
perfused	0
in	0
serum	0
-	0
free	0
media	0
with	0
or	0
without	0
10	0
(	0
-	0
7	0
)	0
M	0
dexamethasone	1
for	0
12	0
days	0
.	0

Intraocular	0
pressure	0
was	0
monitored	0
daily	0
.	0

After	0
incubation	0
,	0
the	0
eyes	0
were	0
morphologically	0
characterized	0
by	0
light	0
microscopy	0
,	0
transmission	0
and	0
scanning	0
electron	0
microscopy	0
,	0
and	0
scanning	0
laser	0
confocal	0
microscopy	0
.	0

RESULTS	0
:	0
A	0
significant	0
increase	0
in	0
intraocular	0
pressure	0
developed	0
in	0
13	0
of	0
the	0
44	0
pairs	0
of	0
eyes	0
perfused	0
with	0
dexamethasone	1
with	0
an	0
average	0
pressure	0
rise	0
of	0
17	0
.	0
5	0
+	0
/	0
-	0
3	0
.	0
8	0
mm	0
Hg	0
after	0
12	0
days	0
of	0
dexamethasone	1
exposure	0
.	0

The	0
contralateral	0
control	0
eyes	0
,	0
which	0
did	0
not	0
receive	0
dexamethasone	1
,	0
maintained	0
a	0
stable	0
intraocular	0
pressure	0
during	0
the	0
same	0
period	0
.	0

The	0
outflow	0
pathway	0
of	0
the	0
untreated	0
eyes	0
appeared	0
morphologically	0
normal	0
.	0

In	0
contrast	0
,	0
the	0
dexamethasone	1
-	0
treated	0
hypertensive	3
eyes	4
had	0
thickened	0
trabecular	0
beams	0
,	0
decreased	0
intertrabecular	0
spaces	0
,	0
thickened	0
juxtacanalicular	0
tissue	0
,	0
activated	0
trabecular	0
meshwork	0
cells	0
,	0
and	0
increased	0
amounts	0
of	0
amorphogranular	0
extracellular	0
material	0
,	0
especially	0
in	0
the	0
juxtacanalicular	0
tissue	0
and	0
beneath	0
the	0
endothelial	0
lining	0
of	0
the	0
canal	0
of	0
Schlemm	0
.	0

The	0
dexamethasone	1
-	0
treated	0
nonresponder	0
eyes	0
appeared	0
to	0
be	0
morphologically	0
similar	0
to	0
the	0
untreated	0
eyes	0
,	0
although	0
several	0
subtle	0
dexamethasone	1
-	0
induced	0
morphologic	0
changes	0
were	0
evident	0
.	0

C0NCLUSI0N	0
:	0
Dexamethasone	1
treatment	0
of	0
isolated	0
,	0
perfusion	0
-	0
cultured	0
human	0
eyes	0
led	0
to	0
the	0
generation	0
of	0
ocular	3
hypertension	4
in	0
approximately	0
30	0
%	0
of	0
the	0
dexamethasone	1
-	0
treated	0
eyes	0
.	0

Steroid	1
treatment	0
resulted	0
in	0
morphologic	0
changes	0
in	0
the	0
trabecular	0
meshwork	0
similar	0
to	0
those	0
reported	0
for	0
corticosteroid	3
glaucoma	4
and	0
open	3
angle	4
glaucoma	4
.	0

This	0
system	0
may	0
provide	0
an	0
acute	0
model	0
in	0
which	0
to	0
study	0
the	0
pathogenic	0
mechanisms	0
involved	0
in	0
steroid	3
glaucoma	4
and	0
primary	3
open	4
angle	4
glaucoma	4
.	0

Auditory	0
disturbance	0
associated	0
with	0
interscalene	0
brachial	0
plexus	0
block	0
.	0

We	0
performed	0
an	0
audiometric	0
study	0
in	0
20	0
patients	0
who	0
underwent	0
surgery	0
of	0
the	0
shoulder	0
region	0
under	0
an	0
interscalene	0
brachial	0
plexus	0
block	0
(	0
IBPB	0
)	0
.	0

Bupivacaine	1
0	0
.	0
75	0
%	0
with	0
adrenaline	1
was	0
given	0
followed	0
by	0
a	0
24	0
-	0
hr	0
continuous	0
infusion	0
of	0
0	0
.	0
25	0
%	0
bupivacaine	1
.	0

Three	0
audiometric	0
threshold	0
measurements	0
(	0
0	0
.	0
25	0
-	0
18	0
kHz	0
)	0
were	0
made	0
:	0
the	0
first	0
before	0
IBPB	0
,	0
the	0
second	0
2	0
-	0
6	0
h	0
after	0
surgery	0
and	0
the	0
third	0
on	0
the	0
first	0
day	0
after	0
operation	0
.	0

In	0
four	0
patients	0
hearing	3
impairment	4
on	0
the	0
side	0
of	0
the	0
block	0
was	0
demonstrated	0
after	0
operation	0
,	0
in	0
three	0
measurements	0
on	0
the	0
day	0
of	0
surgery	0
and	0
in	0
one	0
on	0
the	0
following	0
day	0
.	0

The	0
frequencies	0
at	0
which	0
the	0
impairment	0
occurred	0
varied	0
between	0
patients	0
;	0
in	0
one	0
only	0
low	0
frequencies	0
(	0
0	0
.	0
25	0
-	0
0	0
.	0
5	0
kHz	0
)	0
were	0
involved	0
.	0

The	0
maximum	0
change	0
in	0
threshold	0
was	0
35	0
dB	0
at	0
6	0
kHz	0
measured	0
at	0
the	0
end	0
of	0
the	0
continuous	0
infusion	0
of	0
bupivacaine	1
.	0

This	0
patient	0
had	0
hearing	0
threshold	0
changes	0
(	0
15	0
-	0
20	0
dB	0
)	0
at	0
6	0
-	0
10	0
kHz	0
on	0
the	0
opposite	0
side	0
also	0
.	0

IBPB	0
may	0
cause	0
transient	0
auditory	3
dysfunction	4
in	0
the	0
ipsilateral	0
ear	0
,	0
possibly	0
via	0
an	0
effect	0
on	0
sympathetic	0
innervation	0
.	0

The	0
safety	0
and	0
efficacy	0
of	0
combination	0
N	1
-	2
butyl	2
-	2
deoxynojirimycin	2
(	0
SC	1
-	2
48334	2
)	0
and	0
zidovudine	1
in	0
patients	0
with	0
HIV	3
-	4
1	4
infection	4
and	0
200	0
-	0
500	0
CD4	0
cells	0
/	0
mm3	0
.	0

We	0
conducted	0
a	0
double	0
-	0
blind	0
,	0
randomized	0
phase	0
II	0
study	0
to	0
evaluate	0
the	0
safety	0
and	0
activity	0
of	0
combination	0
therapy	0
with	0
N	1
-	2
butyl	2
-	2
deoxynojirimycin	2
(	0
SC	1
-	2
48334	2
)	0
(	0
an	0
alpha	0
-	0
glucosidase	0
I	0
inhibitor	0
)	0
and	0
zidovudine	1
versus	0
zidovudine	1
alone	0
.	0

Patients	0
with	0
200	0
to	0
500	0
CD4	0
cells	0
/	0
mm3	0
who	0
tolerated	0
<	0
or	0
=	0
12	0
weeks	0
of	0
prior	0
zidovudine	1
therapy	0
received	0
SC	1
-	2
48334	2
(	0
1000	0
mg	0
every	0
8	0
h	0
)	0
and	0
zidovudine	1
(	0
100	0
mg	0
every	0
8	0
h	0
)	0
or	0
zidovudine	1
and	0
placebo	0
.	0

Sixty	0
patients	0
received	0
combination	0
therapy	0
and	0
58	0
,	0
zidovudine	1
and	0
placebo	0
.	0

Twenty	0
-	0
three	0
patients	0
(	0
38	0
%	0
)	0
and	0
15	0
(	0
26	0
%	0
)	0
,	0
in	0
the	0
combination	0
and	0
zidovudine	1
groups	0
,	0
respectively	0
,	0
discontinued	0
therapy	0
(	0
p	0
=	0
0	0
.	0
15	0
)	0
.	0

The	0
mean	0
SC	1
-	2
48334	2
steady	0
-	0
state	0
trough	0
level	0
(	0
4	0
.	0
04	0
+	0
/	0
-	0
0	0
.	0
99	0
micrograms	0
/	0
ml	0
)	0
was	0
below	0
the	0
in	0
vitro	0
inhibitory	0
concentration	0
for	0
human	0
immunodeficiency	3
virus	0
(	0
HIV	0
)	0
.	0

The	0
mean	0
increase	0
in	0
CD4	0
cells	0
at	0
week	0
4	0
was	0
73	0
.	0
8	0
cells	0
/	0
mm3	0
and	0
52	0
.	0
4	0
cells	0
/	0
mm3	0
for	0
the	0
combination	0
and	0
zidovudine	1
groups	0
,	0
respectively	0
(	0
p	0
>	0
0	0
.	0
36	0
)	0
.	0

For	0
patients	0
with	0
prior	0
zidovudine	1
therapy	0
,	0
the	0
mean	0
change	0
in	0
CD4	0
cells	0
in	0
the	0
combination	0
and	0
zidovudine	1
groups	0
was	0
63	0
.	0
7	0
cells	0
/	0
mm3	0
and	0
4	0
.	0
9	0
cells	0
/	0
mm3	0
at	0
week	0
8	0
and	0
6	0
.	0
8	0
cells	0
/	0
mm3	0
and	0
-	0
45	0
.	0
1	0
cells	0
/	0
mm3	0
at	0
week	0
16	0
,	0
respectively	0
.	0

The	0
number	0
of	0
patients	0
with	0
suppression	0
of	0
HIV	0
p24	0
antigenemia	0
in	0
the	0
combination	0
and	0
zidovudine	1
groups	0
was	0
six	0
(	0
40	0
%	0
)	0
and	0
two	0
(	0
11	0
%	0
)	0
at	0
week	0
4	0
(	0
p	0
=	0
0	0
.	0
10	0
)	0
and	0
five	0
(	0
45	0
%	0
)	0
and	0
two	0
(	0
14	0
%	0
)	0
at	0
week	0
24	0
(	0
p	0
=	0
0	0
.	0
08	0
)	0
,	0
respectively	0
.	0

Diarrhea	3
,	0
flatulence	3
,	0
abdominal	3
pain	4
,	0
and	0
weight	3
loss	4
were	0
common	0
for	0
combination	0
recipients	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Prolonged	0
paralysis	3
due	0
to	0
nondepolarizing	1
neuromuscular	2
blocking	2
agents	2
and	0
corticosteroids	1
.	0

The	0
long	0
-	0
term	0
use	0
of	0
nondepolarizing	1
neuromuscular	2
blocking	2
agents	2
(	0
ND	1
-	2
NMBA	2
)	0
has	0
recently	0
been	0
implicated	0
as	0
a	0
cause	0
of	0
prolonged	0
muscle	3
weakness	4
,	0
although	0
the	0
site	0
of	0
the	0
lesion	0
and	0
the	0
predisposing	0
factors	0
have	0
been	0
unclear	0
.	0

We	0
report	0
3	0
patients	0
(	0
age	0
37	0
-	0
52	0
years	0
)	0
with	0
acute	0
respiratory	3
insufficiency	4
who	0
developed	0
prolonged	0
weakness	3
following	0
the	0
discontinuation	0
of	0
ND	1
-	2
NMBAs	2
.	0

Two	0
patients	0
also	0
received	0
intravenous	0
corticosteroids	1
.	0

Renal	0
function	0
was	0
normal	0
but	0
hepatic	0
function	0
was	0
impaired	0
in	0
all	0
patients	0
,	0
and	0
all	0
had	0
acidosis	3
.	0

Electrophysiologic	0
studies	0
revealed	0
low	0
amplitude	0
compound	0
motor	0
action	0
potentials	0
,	0
normal	0
sensory	0
studies	0
,	0
and	0
fibrillations	0
.	0

Repetitive	0
stimulation	0
at	0
2	0
Hz	0
showed	0
a	0
decremental	0
response	0
in	0
2	0
patients	0
.	0

The	0
serum	0
vecuronium	1
level	0
measured	0
in	0
1	0
patient	0
14	0
days	0
after	0
the	0
drug	0
had	0
been	0
discontinued	0
was	0
172	0
ng	0
/	0
mL	0
.	0

A	0
muscle	0
biopsy	0
in	0
this	0
patient	0
showed	0
loss	3
of	4
thick	4
,	4
myosin	4
filaments	4
.	0

The	0
weakness	3
in	0
these	0
patients	0
is	0
due	0
to	0
pathology	3
at	4
both	4
the	4
neuromuscular	4
junction	4
(	0
most	0
likely	0
due	0
to	0
ND	1
-	2
NMBA	2
)	0
and	0
muscle	0
(	0
most	0
likely	0
due	0
to	0
corticosteroids	1
)	0
.	0

Hepatic	3
dysfunction	4
and	0
acidosis	3
are	0
contributing	0
risk	0
factors	0
.	0

Failure	0
of	0
ancrod	0
in	0
the	0
treatment	0
of	0
heparin	1
-	0
induced	0
arterial	0
thrombosis	3
.	0

The	0
morbidity	0
and	0
mortality	0
associated	0
with	0
heparin	1
-	0
induced	0
thrombosis	3
remain	0
high	0
despite	0
numerous	0
empirical	0
therapies	0
.	0

Ancrod	0
has	0
been	0
used	0
successfully	0
for	0
prophylaxis	0
against	0
development	0
of	0
thrombosis	3
in	0
patients	0
with	0
heparin	1
induced	0
platelet	3
aggregation	4
who	0
require	0
brief	0
reexposure	0
to	0
heparin	1
,	0
but	0
its	0
success	0
in	0
patients	0
who	0
have	0
developed	0
the	0
thrombosis	3
syndrome	0
is	0
not	0
well	0
defined	0
.	0

The	0
authors	0
present	0
a	0
case	0
of	0
failure	0
of	0
ancrod	0
treatment	0
in	0
a	0
patient	0
with	0
heparin	1
-	0
induced	0
thrombosis	3
.	0

Water	3
intoxication	4
associated	0
with	0
oxytocin	1
administration	0
during	0
saline	0
-	0
induced	0
abortion	3
.	0

Four	0
cases	0
of	0
water	3
intoxication	4
in	0
connection	0
with	0
oxytocin	1
administration	0
during	0
saline	0
-	0
induced	0
abortions	3
are	0
described	0
.	0

The	0
mechanism	0
of	0
water	3
intoxication	4
is	0
discussed	0
in	0
regard	0
to	0
these	0
cases	0
.	0

0xytocin	1
administration	0
during	0
midtrimester	0
-	0
induced	0
abortions	3
is	0
advocated	0
only	0
if	0
it	0
can	0
be	0
carried	0
out	0
under	0
careful	0
observations	0
of	0
an	0
alert	0
nursing	0
staff	0
,	0
aware	0
of	0
the	0
symptoms	0
of	0
water	3
intoxication	4
and	0
instructed	0
to	0
watch	0
the	0
diuresis	0
and	0
report	0
such	0
early	0
signs	0
of	0
the	0
syndrome	0
as	0
asthenia	3
,	0
muscular	0
irritability	3
,	0
or	0
headaches	3
.	0

The	0
oxytocin	1
should	0
be	0
given	0
only	0
in	0
Ringers	0
lactate	1
or	0
,	0
alternately	0
,	0
in	0
Ringers	0
lactate	1
and	0
a	0
5	0
per	0
cent	0
dextrose	1
and	0
water	0
solutions	0
.	0

The	0
urinary	0
output	0
should	0
be	0
monitored	0
and	0
the	0
oxytocin	1
administration	0
discontinued	0
and	0
the	0
serum	0
electrolytes	0
checked	0
if	0
the	0
urinary	0
output	0
decreases	0
.	0

The	0
oxytocin	1
should	0
not	0
be	0
administered	0
in	0
excess	0
of	0
36	0
hours	0
.	0

If	0
the	0
patient	0
has	0
not	0
aborted	0
by	0
then	0
the	0
oxytocin	1
should	0
be	0
discontinued	0
for	0
10	0
to	0
12	0
hours	0
in	0
order	0
to	0
perform	0
electrolyte	0
determinations	0
and	0
correct	0
any	0
electrolyte	0
imbalance	0
.	0

Light	0
chain	0
proteinuria	3
and	0
cellular	0
mediated	0
immunity	0
in	0
rifampin	1
treated	0
patients	0
with	0
tuberculosis	3
.	0

Light	0
chain	0
proteinuria	3
was	0
found	0
in	0
9	0
of	0
17	0
tuberculosis	3
patients	0
treated	0
with	0
rifampin	1
.	0

Concomitant	0
assay	0
of	0
cellular	0
mediated	0
immunity	0
in	0
these	0
patients	0
using	0
skin	0
test	0
antigen	0
and	0
a	0
lymphokine	0
in	0
vitro	0
test	0
provided	0
results	0
that	0
were	0
different	0
.	0

Response	0
to	0
Varidase	0
skin	0
test	0
antigen	0
was	0
negative	0
for	0
all	0
eight	0
tuberculosis	3
patients	0
tested	0
,	0
but	0
there	0
occurred	0
a	0
hyper	0
-	0
responsiveness	0
of	0
the	0
lymphocytes	0
of	0
these	0
eight	0
patients	0
to	0
phytomitogen	0
(	0
PHA	0
-	0
P	0
)	0
.	0
as	0
well	0
as	0
of	0
those	0
of	0
seven	0
other	0
tuberculous	3
patients	0
.	0

This	0
last	0
finding	0
may	0
be	0
related	0
to	0
time	0
of	0
testing	0
and	0
/	0
or	0
endogenous	0
serum	0
binding	0
of	0
rifampin	1
which	0
could	0
have	0
inhibited	0
mitogen	0
activity	0
for	0
the	0
lymphocyte	0
.	0

KF17837	1
:	0
a	0
novel	0
selective	0
adenosine	1
A2A	0
receptor	0
antagonist	0
with	0
anticataleptic	0
activity	0
.	0

KF17837	1
is	0
a	0
novel	0
selective	0
adenosine	1
A2A	0
receptor	0
antagonist	0
.	0

0ral	0
administration	0
of	0
KF17837	1
(	0
2	0
.	0
5	0
,	0
10	0
.	0
0	0
and	0
30	0
.	0
0	0
mg	0
/	0
kg	0
)	0
significantly	0
ameliorated	0
the	0
cataleptic	3
responses	0
induced	0
by	0
intracerebroventricular	0
administration	0
of	0
an	0
adenosine	1
A2A	0
receptor	0
agonist	0
,	0
CGS	1
21680	2
(	0
10	0
micrograms	0
)	0
,	0
in	0
a	0
dose	0
-	0
dependent	0
manner	0
.	0

KF17837	1
also	0
reduced	0
the	0
catalepsy	3
induced	0
by	0
haloperidol	1
(	0
1	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
and	0
by	0
reserpine	1
(	0
5	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
.	0

These	0
anticataleptic	0
effects	0
were	0
exhibited	0
dose	0
dependently	0
at	0
doses	0
from	0
0	0
.	0
625	0
and	0
2	0
.	0
5	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
,	0
respectively	0
.	0

Moreover	0
,	0
KF17837	1
(	0
0	0
.	0
625	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
)	0
potentiated	0
the	0
anticataleptic	0
effects	0
of	0
a	0
subthreshold	0
dose	0
of	0
L	1
-	2
3	2
,	2
4	2
-	2
dihydroxyphenylalanine	2
(	0
L	1
-	2
D0PA	2
;	0
25	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
plus	0
benserazide	1
(	0
6	0
.	0
25	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
.	0

These	0
results	0
suggested	0
that	0
KF17837	1
is	0
a	0
centrally	0
active	0
adenosine	1
A2A	0
receptor	0
antagonist	0
and	0
that	0
the	0
dopaminergic	0
function	0
of	0
the	0
nigrostriatal	0
pathway	0
is	0
potentiated	0
by	0
adenosine	1
A2A	0
receptor	0
antagonists	0
.	0

Furthermore	0
,	0
KF17837	1
may	0
be	0
a	0
useful	0
drug	0
in	0
the	0
treatment	0
of	0
parkinsonism	3
.	0

Effect	0
of	0
nondopaminergic	0
drugs	0
on	0
L	1
-	2
dopa	2
-	0
induced	0
dyskinesias	3
in	0
MPTP	1
-	0
treated	0
monkeys	0
.	0

A	0
group	0
of	0
four	0
monkeys	0
was	0
rendered	0
parkinsonian	3
with	0
the	0
toxin	0
MPTP	1
.	0

They	0
were	0
then	0
treated	0
chronically	0
with	0
L	1
-	2
D0PA	2
/	2
benserazide	2
50	0
/	0
12	0
.	0
5	0
mg	0
/	0
kg	0
given	0
orally	0
daily	0
for	0
2	0
months	0
.	0

This	0
dose	0
produced	0
a	0
striking	0
antiparkinsonian	0
effect	0
,	0
but	0
all	0
animals	0
manifested	0
dyskinesia	3
.	0

A	0
series	0
of	0
agents	0
acting	0
primarily	0
on	0
neurotransmitters	0
other	0
than	0
dopamine	1
were	0
then	0
tested	0
in	0
combination	0
with	0
L	1
-	2
D0PA	2
to	0
see	0
if	0
the	0
dyskinetic	3
movements	0
would	0
be	0
modified	0
.	0

Several	0
drugs	0
,	0
including	0
clonidine	1
,	0
physostigmine	1
,	0
methysergide	1
,	0
5	1
-	2
MD0T	2
,	0
propranolol	1
,	0
and	0
MK	1
-	2
801	2
,	0
markedly	0
reduced	0
the	0
dyskinetic	3
movements	0
but	0
at	0
the	0
cost	0
of	0
a	0
return	0
of	0
parkinsonian	3
symptomatology	0
.	0

However	0
,	0
yohimbine	1
and	0
meperidine	1
reduced	0
predominantly	0
the	0
dyskinetic	3
movements	0
.	0

Baclofen	1
was	0
also	0
useful	0
in	0
one	0
monkey	0
against	0
a	0
more	0
dystonic	3
form	0
of	0
dyskinesia	3
.	0

Atropine	1
converted	0
the	0
dystonic	3
movements	0
into	0
chorea	3
.	0

Hallucinations	3
and	0
ifosfamide	1
-	0
induced	0
neurotoxicity	3
.	0

BACKGR0UND	0
:	0
Hallucinations	3
as	0
a	0
symptom	0
of	0
central	0
neurotoxicity	3
are	0
a	0
known	0
but	0
poorly	0
described	0
side	0
effect	0
of	0
ifosfamide	1
.	0

Most	0
cases	0
of	0
ifosfamide	1
-	0
induced	0
hallucinations	3
have	0
been	0
reported	0
with	0
other	0
mental	0
status	0
changes	0
.	0

METH0DS	0
:	0
The	0
authors	0
interviewed	0
six	0
persons	0
with	0
ifosfamide	1
-	0
induced	0
hallucinations	3
in	0
the	0
presence	0
of	0
a	0
clear	0
sensorium	0
.	0

All	0
patients	0
were	0
receiving	0
high	0
-	0
dose	0
ifosfamide	1
as	0
part	0
of	0
their	0
bone	0
marrow	0
transplant	0
procedure	0
.	0

RESULTS	0
:	0
Hallucinations	3
occurred	0
only	0
when	0
the	0
patient	0
'	0
s	0
eyes	0
were	0
closed	0
and	0
,	0
in	0
all	0
but	0
one	0
case	0
,	0
were	0
reported	0
as	0
disturbing	0
or	0
frightening	0
.	0

Underreporting	0
of	0
these	0
hallucinations	3
by	0
patients	0
is	0
likely	0
.	0

C0NCLUSI0NS	0
:	0
Hallucinations	3
may	0
be	0
the	0
sole	0
or	0
first	0
manifestation	0
of	0
neurotoxicity	3
.	0

The	0
incidence	0
may	0
be	0
dose	0
and	0
infusion	0
-	0
time	0
related	0
.	0

The	0
clinician	0
should	0
be	0
alerted	0
for	0
possible	0
ifosfamide	1
-	0
induced	0
hallucinations	3
,	0
which	0
may	0
occur	0
without	0
other	0
signs	0
of	0
neurotoxicity	3
.	0

"	0
Eyes	0
-	0
closed	0
"	0
hallucinatory	3
experiences	0
appear	0
to	0
be	0
an	0
unusual	0
feature	0
of	0
this	0
presentation	0
.	0

Patients	0
anxious	0
about	0
this	0
experience	0
respond	0
well	0
to	0
support	0
and	0
education	0
about	0
this	0
occurrence	0
.	0

0ptimal	0
pharmacologic	0
management	0
of	0
disturbed	0
patients	0
is	0
unclear	0
.	0

If	0
agitation	3
becomes	0
marked	0
,	0
high	0
-	0
potency	0
neuroleptics	0
(	0
i	0
.	0
e	0
.	0
,	0
haloperidol	1
)	0
may	0
be	0
effective	0
.	0

Photodistributed	0
nifedipine	1
-	0
induced	0
facial	0
telangiectasia	3
.	0

Five	0
months	0
after	0
starting	0
nifedipine	1
(	0
Adalat	1
)	0
,	0
two	0
patients	0
developed	0
photodistributed	0
facial	0
telangiectasia	3
,	0
which	0
became	0
more	0
noticeable	0
with	0
time	0
.	0

Neither	0
patient	0
complained	0
of	0
photosensitivity	0
or	0
flushing	3
.	0

Both	0
patients	0
reported	0
a	0
significant	0
cosmetic	0
improvement	0
after	0
discontinuing	0
the	0
drug	0
.	0

0ne	0
commenced	0
the	0
closely	0
related	0
drug	0
amlodipine	1
3	0
years	0
later	0
,	0
with	0
recurrence	0
of	0
telangiectasia	3
.	0

The	0
photodistribution	0
of	0
the	0
telangiectasia	3
suggests	0
a	0
significant	0
drug	0
/	0
light	0
interaction	0
.	0

Penicillamine	1
-	0
induced	0
rapidly	0
progressive	0
glomerulonephritis	3
in	0
a	0
patient	0
with	0
rheumatoid	3
arthritis	4
.	0

A	0
67	0
-	0
year	0
-	0
old	0
woman	0
with	0
rheumatoid	3
arthritis	4
presented	0
rapidly	0
progressive	0
glomerulonephritis	3
(	0
RPGN	3
)	0
after	0
5	0
months	0
of	0
D	1
-	2
penicillamine	2
(	0
250	0
mg	0
/	0
day	0
)	0
treatment	0
.	0

Light	0
microscopy	0
study	0
showed	0
severe	0
glomerulonephritis	3
with	0
crescent	0
formation	0
in	0
60	0
%	0
of	0
the	0
glomeruli	0
and	0
infiltration	0
of	0
inflammatory	0
cells	0
in	0
the	0
wall	0
of	0
an	0
arteriole	0
.	0

Immunofluorescence	0
revealed	0
scanty	0
granular	0
IgG	0
,	0
IgA	0
and	0
C3	0
deposits	0
along	0
the	0
capillary	0
walls	0
and	0
mesangium	0
.	0

The	0
patient	0
was	0
treated	0
with	0
steroid	1
pulse	0
,	0
plasmapheresis	0
,	0
cyclophosphamide	1
and	0
antiplatelet	1
agents	2
.	0

A	0
complete	0
recovery	0
of	0
renal	0
function	0
was	0
achieved	0
in	0
a	0
few	0
weeks	0
.	0

This	0
new	0
case	0
of	0
RPGN	3
in	0
the	0
course	0
of	0
D	1
-	2
penicillamine	2
treatment	0
emphasizes	0
the	0
need	0
for	0
frequent	0
monitoring	0
of	0
renal	0
function	0
and	0
evaluation	0
of	0
urinary	0
sediment	0
and	0
proteinuria	3
in	0
these	0
patients	0
.	0

The	0
prompt	0
discontinuation	0
of	0
D	1
-	2
penicillamine	2
and	0
vigorous	0
treatment	0
measures	0
could	0
allow	0
for	0
a	0
good	0
prognosis	0
as	0
in	0
this	0
case	0
.	0

A	0
case	0
of	0
polymyositis	3
in	0
a	0
patient	0
with	0
primary	3
biliary	4
cirrhosis	4
treated	0
with	0
D	1
-	2
penicillamine	2
.	0

Although	0
D	1
-	2
penicillamine	2
has	0
been	0
used	0
for	0
many	0
rheumatologic	3
diseases	4
,	0
toxicity	3
limits	0
its	0
usefulness	0
in	0
many	0
patients	0
.	0

Polymyositis	3
/	0
dermatomyositis	3
can	0
develop	0
as	0
one	0
of	0
the	0
autoimmune	0
complications	0
of	0
D	1
-	2
penicillamine	2
treatment	0
,	0
but	0
its	0
exact	0
pathogenesis	0
remains	0
unclear	0
.	0

We	0
report	0
a	0
patient	0
with	0
primary	3
biliary	4
cirrhosis	4
,	0
who	0
developed	0
polymyositis	3
while	0
receiving	0
D	1
-	2
penicillamine	2
therapy	0
.	0

We	0
described	0
the	0
special	0
clinical	0
course	0
of	0
the	0
patient	0
.	0

Patients	0
receiving	0
D	1
-	2
penicillamine	2
therapy	0
should	0
be	0
followed	0
carefully	0
for	0
the	0
development	0
of	0
autoimmune	0
complications	0
like	0
polymyositis	3
/	0
dermatomyositis	3
.	0

Hyperalgesia	3
and	0
myoclonus	3
in	0
terminal	0
cancer	3
patients	0
treated	0
with	0
continuous	0
intravenous	0
morphine	1
.	0

Eight	0
cancer	3
patients	0
in	0
the	0
terminal	0
stages	0
of	0
the	0
disease	0
treated	0
with	0
high	0
doses	0
of	0
intravenous	0
morphine	1
developed	0
hyperalgesia	3
.	0

All	0
cases	0
were	0
retrospectively	0
sampled	0
from	0
three	0
different	0
hospitals	0
in	0
Copenhagen	0
.	0

Five	0
patients	0
developed	0
universal	0
hyperalgesia	3
and	0
hyperesthesia	3
which	0
in	0
2	0
cases	0
were	0
accompanied	0
by	0
myoclonus	3
.	0

In	0
3	0
patients	0
a	0
pre	0
-	0
existing	0
neuralgia	3
increased	0
to	0
excruciating	0
intensity	0
and	0
in	0
2	0
of	0
these	0
cases	0
myoclonus	3
occurred	0
simultaneously	0
.	0

Although	0
only	0
few	0
clinical	0
descriptions	0
of	0
the	0
relationship	0
between	0
hyperalgesia	3
/	0
myoclonus	3
and	0
high	0
doses	0
of	0
morphine	1
are	0
available	0
,	0
experimental	0
support	0
from	0
animal	0
studies	0
indicates	0
that	0
morphine	1
,	0
or	0
its	0
metabolites	0
,	0
plays	0
a	0
causative	0
role	0
for	0
the	0
observed	0
behavioural	0
syndrome	0
.	0

The	0
possible	0
mechanisms	0
are	0
discussed	0
and	0
treatment	0
proposals	0
given	0
suggesting	0
the	0
use	0
of	0
more	0
efficacious	0
opioids	0
with	0
less	0
excitatory	0
potency	0
in	0
these	0
situations	0
.	0

Liposomal	0
daunorubicin	1
in	0
advanced	0
Kaposi	3
'	4
s	4
sarcoma	4
:	0
a	0
phase	0
II	0
study	0
.	0

We	0
report	0
a	0
non	0
-	0
randomized	0
Phase	0
II	0
clinical	0
trial	0
to	0
assess	0
the	0
efficacy	0
and	0
safety	0
of	0
liposomal	0
daunorubicin	1
(	0
DaunoXome	0
)	0
in	0
the	0
treatment	0
of	0
AIDS	3
related	0
Kaposi	3
'	4
s	4
sarcoma	4
.	0

Eleven	0
homosexual	0
men	0
with	0
advanced	0
Kaposi	3
'	4
s	4
sarcoma	4
were	0
entered	0
in	0
the	0
trial	0
.	0

Changes	0
in	0
size	0
,	0
colour	0
and	0
associated	0
oedema	3
of	0
selected	0
'	0
target	0
'	0
lesions	0
were	0
measured	0
.	0

Clinical	0
,	0
biochemical	0
and	0
haematological	0
toxicities	3
were	0
assessed	0
.	0

Ten	0
subjects	0
were	0
evaluated	0
.	0

A	0
partial	0
response	0
was	0
achieved	0
in	0
four	0
,	0
of	0
whom	0
two	0
subsequently	0
relapsed	0
.	0

Stabilization	0
of	0
Kaposi	3
'	4
s	4
sarcoma	4
occurred	0
in	0
the	0
remaining	0
six	0
,	0
maintained	0
until	0
the	0
end	0
of	0
the	0
trial	0
period	0
in	0
four	0
.	0

The	0
drug	0
was	0
generally	0
well	0
tolerated	0
,	0
with	0
few	0
mild	0
symptoms	0
of	0
toxicity	3
.	0

The	0
main	0
problem	0
encountered	0
was	0
haematological	0
toxicity	3
,	0
with	0
three	0
subjects	0
experiencing	0
severe	0
neutropenia	3
(	0
neutrophil	0
count	0
<	0
0	0
.	0
5	0
x	0
10	0
(	0
9	0
)	0
/	0
l	0
)	0
.	0

There	0
was	0
no	0
evidence	0
of	0
cardiotoxicity	3
.	0

In	0
this	0
small	0
patient	0
sample	0
,	0
liposomal	0
daunorubicin	1
was	0
an	0
effective	0
and	0
well	0
tolerated	0
agent	0
in	0
the	0
treatment	0
of	0
Kaposi	3
'	4
s	4
sarcoma	4
.	0

Long	0
-	0
term	0
effects	0
of	0
vincristine	1
on	0
the	0
peripheral	0
nervous	0
system	0
.	0

Forty	0
patients	0
with	0
Non	3
-	4
Hodgkin	4
'	4
s	4
Lymphoma	4
treated	0
with	0
vincristine	1
between	0
1984	0
and	0
1990	0
(	0
cumulative	0
dose	0
12	0
mg	0
in	0
18	0
-	0
24	0
weeks	0
)	0
were	0
investigated	0
in	0
order	0
to	0
evaluate	0
the	0
long	0
term	0
effects	0
of	0
vincristine	1
on	0
the	0
peripheral	0
nervous	0
system	0
.	0

The	0
patients	0
were	0
interviewed	0
with	0
emphasis	0
on	0
neuropathic	3
symptoms	4
.	0

Physical	0
and	0
quantitative	0
sensory	0
examination	0
with	0
determination	0
of	0
vibratory	0
perception	0
and	0
thermal	0
discrimination	0
thresholds	0
were	0
performed	0
,	0
four	0
to	0
77	0
months	0
(	0
median	0
34	0
months	0
)	0
after	0
vincristine	1
treatment	0
.	0

Twenty	0
-	0
seven	0
patients	0
reported	0
neuropathic	3
symptoms	4
.	0

In	0
13	0
of	0
these	0
27	0
patients	0
symptoms	0
were	0
still	0
present	0
at	0
the	0
time	0
of	0
examination	0
.	0

In	0
these	0
patients	0
sensory	0
signs	0
and	0
symptoms	0
predominated	0
.	0

In	0
the	0
other	0
14	0
patients	0
symptoms	0
had	0
been	0
present	0
in	0
the	0
past	0
.	0

Symptoms	0
persisted	0
maximally	0
40	0
months	0
since	0
cessation	0
of	0
therapy	0
.	0

There	0
was	0
no	0
age	0
difference	0
between	0
patients	0
with	0
and	0
without	0
complaints	0
at	0
the	0
time	0
of	0
examination	0
.	0

Normal	0
reflexes	0
were	0
found	0
in	0
two	0
third	0
of	0
patients	0
.	0

Neuropathic	0
complaints	0
were	0
not	0
very	0
troublesome	0
on	0
the	0
long	0
term	0
.	0

It	0
is	0
concluded	0
that	0
with	0
the	0
above	0
mentioned	0
vincristine	1
dose	0
schedule	0
signs	0
and	0
symptoms	0
of	0
vincristine	1
neuropathy	3
are	0
reversible	0
for	0
a	0
great	0
deal	0
and	0
prognosis	0
is	0
fairly	0
good	0
.	0

Hepatic	0
adenomas	3
and	0
focal	3
nodular	4
hyperplasia	4
of	0
the	0
liver	0
in	0
young	0
women	0
on	0
oral	1
contraceptives	2
:	0
case	0
reports	0
.	0

Two	0
cases	0
of	0
hepatic	0
adenoma	3
and	0
one	0
of	0
focal	3
nodular	4
hyperplasia	4
presumably	0
associated	0
with	0
the	0
use	0
of	0
oral	1
contraceptives	2
,	0
are	0
reported	0
.	0

Special	0
reference	0
is	0
made	0
to	0
their	0
clinical	0
presentation	0
,	0
which	0
may	0
be	0
totally	0
asymptomatic	0
.	0

Liver	0
-	0
function	0
tests	0
are	0
of	0
little	0
diagnostic	0
value	0
,	0
but	0
valuable	0
information	0
may	0
be	0
obtained	0
from	0
both	0
liver	0
scanning	0
and	0
hepatic	0
angiography	0
.	0

Histologic	0
differences	0
and	0
clinical	0
similarities	0
between	0
hepatic	0
adenoma	3
and	0
focal	3
nodular	4
hyperplasia	4
of	0
the	0
liver	0
are	0
discussed	0
.	0

Loss	0
of	0
glutamate	1
decarboxylase	0
mRNA	0
-	0
containing	0
neurons	0
in	0
the	0
rat	0
dentate	0
gyrus	0
following	0
pilocarpine	1
-	0
induced	0
seizures	3
.	0

In	0
situ	0
hybridization	0
methods	0
were	0
used	0
to	0
determine	0
if	0
glutamic	1
acid	2
decarboxylase	0
(	0
GAD	0
)	0
mRNA	0
-	0
containing	0
neurons	0
within	0
the	0
hilus	0
of	0
the	0
dentate	0
gyrus	0
are	0
vulnerable	0
to	0
seizure	3
-	0
induced	0
damage	0
in	0
a	0
model	0
of	0
chronic	0
seizures	3
.	0

Sprague	0
-	0
Dawley	0
rats	0
were	0
injected	0
intraperitoneally	0
with	0
pilocarpine	1
,	0
and	0
the	0
hippocampal	0
formation	0
was	0
studied	0
histologically	0
at	0
1	0
,	0
2	0
,	0
4	0
,	0
and	0
8	0
week	0
intervals	0
after	0
pilocarpine	1
-	0
induced	0
seizures	3
.	0

In	0
situ	0
hybridization	0
histochemistry	0
,	0
using	0
a	0
digoxigenin	1
-	0
labeled	0
GAD	0
cRNA	0
probe	0
,	0
demonstrated	0
a	0
substantial	0
decrease	0
in	0
the	0
number	0
of	0
GAD	0
mRNA	0
-	0
containing	0
neurons	0
in	0
the	0
hilus	0
of	0
the	0
dentate	0
gyrus	0
in	0
the	0
pilocarpine	1
-	0
treated	0
rats	0
as	0
compared	0
to	0
controls	0
at	0
all	0
time	0
intervals	0
.	0

Additional	0
neuronanatomical	0
studies	0
,	0
including	0
cresyl	1
violet	2
staining	0
,	0
neuronal	3
degeneration	4
methods	0
,	0
and	0
histochemical	0
localization	0
of	0
glial	0
fibrillary	0
acidic	0
protein	0
,	0
suggested	0
that	0
the	0
decrease	0
in	0
the	0
number	0
of	0
GAD	0
mRNA	0
-	0
containing	0
neurons	0
was	0
related	0
to	0
neuronal	3
loss	4
rather	0
than	0
to	0
a	0
decrease	0
in	0
GAD	0
mRNA	0
levels	0
.	0

The	0
loss	0
of	0
GAD	0
mRNA	0
-	0
containing	0
neurons	0
in	0
the	0
hilus	0
contrasted	0
with	0
the	0
relative	0
preservation	0
of	0
labeled	0
putative	0
basket	0
cells	0
along	0
the	0
inner	0
margin	0
of	0
the	0
granule	0
cell	0
layer	0
.	0

Quantitative	0
analyses	0
of	0
labeled	0
neurons	0
in	0
three	0
regions	0
of	0
the	0
dentate	0
gyrus	0
in	0
the	0
1	0
and	0
2	0
week	0
groups	0
showed	0
statistically	0
significant	0
decreases	0
in	0
the	0
mean	0
number	0
of	0
GAD	0
mRNA	0
-	0
containing	0
neurons	0
in	0
the	0
hilus	0
of	0
both	0
groups	0
of	0
experimental	0
animals	0
.	0

No	0
significant	0
differences	0
were	0
found	0
in	0
the	0
molecular	0
layer	0
or	0
the	0
granule	0
cell	0
layer	0
,	0
which	0
included	0
labeled	0
neurons	0
along	0
the	0
lower	0
margin	0
of	0
the	0
granule	0
cell	0
layer	0
.	0

The	0
results	0
indicate	0
that	0
,	0
in	0
this	0
model	0
,	0
a	0
subpopulation	0
of	0
GAD	0
mRNA	0
-	0
containing	0
neurons	0
within	0
the	0
dentate	0
gyrus	0
is	0
selectively	0
vulnerable	0
to	0
seizure	3
-	0
induced	0
damage	0
.	0

Such	0
differential	0
vulnerability	0
appears	0
to	0
be	0
another	0
indication	0
of	0
the	0
heterogeneity	0
of	0
GABA	1
neurons	0
.	0

Effects	0
of	0
deliberate	0
hypotension	3
induced	0
by	0
labetalol	1
with	0
isoflurane	1
on	0
neuropsychological	0
function	0
.	0

The	0
effect	0
of	0
deliberate	0
hypotension	3
on	0
brain	0
function	0
measured	0
by	0
neuropsychological	0
tests	0
was	0
studied	0
in	0
41	0
adult	0
patients	0
.	0

Twenty	0
-	0
four	0
patients	0
were	0
anaesthetized	0
for	0
middle	0
-	0
ear	0
surgery	0
with	0
deliberate	0
hypotension	3
induced	0
by	0
labetalol	1
with	0
isoflurane	1
(	0
hypotensive	3
group	0
)	0
.	0

Seventeen	0
patients	0
without	0
hypotension	3
served	0
as	0
a	0
control	0
group	0
.	0

The	0
mean	0
arterial	0
pressure	0
was	0
77	0
+	0
/	0
-	0
2	0
mmHg	0
(	0
10	0
.	0
3	0
+	0
/	0
-	0
0	0
.	0
3	0
kPa	0
)	0
before	0
hypotension	3
and	0
50	0
+	0
/	0
-	0
0	0
mmHg	0
(	0
6	0
.	0
7	0
+	0
/	0
-	0
0	0
.	0
0	0
kPa	0
)	0
during	0
hypotension	3
in	0
the	0
hypotensive	3
group	0
,	0
and	0
86	0
+	0
/	0
-	0
2	0
mmHg	0
(	0
11	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
3	0
kPa	0
)	0
during	0
anaesthesia	0
in	0
the	0
control	0
group	0
.	0

The	0
following	0
psychological	0
tests	0
were	0
performed	0
:	0
four	0
subtests	0
of	0
the	0
Wechsler	0
Adult	0
Intelligence	0
Scale	0
(	0
similarities	0
,	0
digit	0
span	0
,	0
vocabulary	0
and	0
digit	0
symbol	0
)	0
,	0
Trail	0
-	0
Making	0
tests	0
A	0
and	0
B	0
,	0
Zung	0
tests	0
(	0
self	0
-	0
rating	0
anxiety	3
scale	0
and	0
self	0
-	0
rating	0
depression	3
scale	0
)	0
and	0
two	0
-	0
part	0
memory	0
test	0
battery	0
with	0
immediate	0
and	0
delayed	0
recall	0
.	0

The	0
tests	0
were	0
performed	0
preoperatively	0
and	0
2	0
days	0
postoperatively	0
.	0

There	0
were	0
no	0
statistically	0
significant	0
differences	0
between	0
the	0
groups	0
in	0
any	0
of	0
the	0
tests	0
in	0
the	0
changes	0
from	0
preoperative	0
value	0
to	0
postoperative	0
value	0
.	0

The	0
results	0
indicate	0
that	0
hypotension	3
induced	0
by	0
labetalol	1
with	0
isoflurane	1
has	0
no	0
significant	0
harmful	0
effects	0
on	0
mental	0
functions	0
compared	0
to	0
normotensive	0
anaesthesia	0
.	0

Apparent	0
cure	0
of	0
rheumatoid	3
arthritis	4
by	0
bone	0
marrow	0
transplantation	0
.	0

We	0
describe	0
the	0
induction	0
of	0
sustained	0
remissions	0
and	0
possible	0
cure	0
of	0
severe	0
erosive	0
rheumatoid	3
arthritis	4
(	0
RA	3
)	0
by	0
bone	0
marrow	0
transplantation	0
(	0
BMT	0
)	0
in	0
2	0
patients	0
.	0

BMT	0
was	0
used	0
to	0
treat	0
severe	0
aplastic	3
anemia	4
which	0
was	0
caused	0
by	0
gold	1
in	0
one	0
case	0
and	0
D	1
-	2
penicillamine	2
in	0
the	0
other	0
.	0

In	0
the	0
8	0
and	0
6	0
years	0
since	0
the	0
transplants	0
(	0
representing	0
8	0
and	0
4	0
years	0
since	0
cessation	0
of	0
all	0
immunosuppressive	0
therapy	0
,	0
respectively	0
)	0
,	0
the	0
RA	3
in	0
each	0
case	0
has	0
been	0
completely	0
quiescent	0
.	0

Although	0
short	0
term	0
remission	0
of	0
severe	0
RA	3
following	0
BMT	0
has	0
been	0
reported	0
,	0
these	0
are	0
the	0
first	0
cases	0
for	0
which	0
prolonged	0
followup	0
has	0
been	0
available	0
.	0

This	0
experience	0
raises	0
the	0
question	0
of	0
the	0
role	0
of	0
BMT	0
itself	0
as	0
a	0
therapeutic	0
option	0
for	0
patients	0
with	0
uncontrolled	0
destructive	0
synovitis	3
.	0

Seizures	3
induced	0
by	0
combined	0
levomepromazine	1
-	0
fluvoxamine	1
treatment	0
.	0

We	0
report	0
a	0
case	0
of	0
combined	0
levomepromazine	1
-	0
fluvoxamine	1
treatment	0
-	0
induced	0
seizures	3
.	0

It	0
seems	0
that	0
combined	0
treatment	0
of	0
fluvoxamine	1
with	0
phenothiazines	1
may	0
possess	0
proconvulsive	0
activity	0
.	0

Case	0
report	0
:	0
pentamidine	1
and	0
polymorphic	0
ventricular	3
tachycardia	4
revisited	0
.	0

Pentamidine	1
isethionate	2
has	0
been	0
associated	0
with	0
ventricular	3
tachyarrhythmias	4
,	0
including	0
torsade	3
de	4
pointes	4
.	0

This	0
article	0
reports	0
two	0
cases	0
of	0
this	0
complication	0
and	0
reviews	0
all	0
reported	0
cases	0
to	0
date	0
.	0

Pentamidine	1
-	0
induced	0
torsade	3
de	4
pointes	4
may	0
be	0
related	0
to	0
serum	0
magnesium	1
levels	0
and	0
hypomagnesemia	3
may	0
synergistically	0
induce	0
torsade	0
.	0

Torsade	3
de	4
pointes	4
occurred	0
after	0
an	0
average	0
of	0
10	0
days	0
of	0
treatment	0
with	0
pentamidine	1
.	0

In	0
these	0
patients	0
,	0
no	0
other	0
acute	0
side	0
effects	0
of	0
pentamidine	1
were	0
observed	0
.	0

Torsade	3
de	4
pointes	4
can	0
be	0
treated	0
when	0
recognized	0
early	0
,	0
possibly	0
without	0
discontinuation	0
of	0
pentamidine	1
.	0

When	0
QTc	3
interval	4
prolongation	4
is	0
observed	0
,	0
early	0
magnesium	1
supplementation	0
is	0
advocated	0
.	0

Efficacy	0
and	0
tolerability	0
of	0
lovastatin	1
in	0
3390	0
women	0
with	0
moderate	0
hypercholesterolemia	3
.	0

0BJECTIVE	0
:	0
To	0
evaluate	0
the	0
efficacy	0
and	0
safety	0
of	0
lovastatin	1
in	0
women	0
with	0
moderate	0
hypercholesterolemia	3
.	0

DESIGN	0
:	0
The	0
Expanded	0
Clinical	0
Evaluation	0
of	0
Lovastatin	1
(	0
EXCEL	0
)	0
Study	0
,	0
a	0
multicenter	0
,	0
double	0
-	0
blind	0
,	0
diet	0
-	0
and	0
placebo	0
-	0
controlled	0
trial	0
,	0
in	0
which	0
participants	0
were	0
randomly	0
assigned	0
to	0
receive	0
placebo	0
or	0
lovastatin	1
at	0
doses	0
of	0
20	0
or	0
40	0
mg	0
once	0
daily	0
,	0
or	0
20	0
or	0
40	0
mg	0
twice	0
daily	0
for	0
48	0
weeks	0
.	0

SETTING	0
:	0
Ambulatory	0
patients	0
recruited	0
by	0
362	0
participating	0
centers	0
throughout	0
the	0
United	0
States	0
.	0

PATIENTS	0
:	0
Women	0
(	0
n	0
=	0
3390	0
)	0
from	0
the	0
total	0
cohort	0
of	0
8245	0
volunteers	0
.	0

MEASUREMENTS	0
:	0
Plasma	0
total	0
,	0
low	0
-	0
density	0
lipoprotein	0
(	0
LDL	0
)	0
,	0
and	0
high	0
-	0
density	0
lipoprotein	0
(	0
HDL	0
)	0
cholesterol	1
,	0
and	0
triglycerides	1
;	0
and	0
laboratory	0
and	0
clinical	0
evidence	0
of	0
adverse	0
events	0
monitored	0
periodically	0
throughout	0
the	0
study	0
.	0

RESULTS	0
:	0
Among	0
women	0
,	0
lovastatin	1
(	0
20	0
to	0
80	0
mg	0
/	0
d	0
)	0
produced	0
sustained	0
(	0
12	0
-	0
to	0
48	0
-	0
week	0
)	0
,	0
dose	0
-	0
related	0
changes	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
:	0
decreases	0
in	0
LDL	0
cholesterol	1
(	0
24	0
%	0
to	0
40	0
%	0
)	0
and	0
triglycerides	1
(	0
9	0
%	0
to	0
18	0
%	0
)	0
,	0
and	0
increases	0
in	0
HDL	0
cholesterol	1
(	0
6	0
.	0
7	0
%	0
to	0
8	0
.	0
6	0
%	0
)	0
.	0

Depending	0
on	0
the	0
dose	0
,	0
from	0
82	0
%	0
to	0
95	0
%	0
of	0
lovastatin	1
-	0
treated	0
women	0
achieved	0
the	0
National	0
Cholesterol	1
Education	0
Program	0
goal	0
of	0
LDL	0
cholesterol	1
levels	0
less	0
than	0
4	0
.	0
14	0
mmol	0
/	0
L	0
(	0
160	0
mg	0
/	0
dL	0
)	0
,	0
and	0
40	0
%	0
to	0
87	0
%	0
achieved	0
the	0
goal	0
of	0
3	0
.	0
36	0
mmol	0
/	0
L	0
(	0
130	0
mg	0
/	0
dL	0
)	0
.	0

Successive	0
transaminase	0
elevations	0
greater	0
than	0
three	0
times	0
the	0
upper	0
limit	0
of	0
normal	0
occurred	0
in	0
0	0
.	0
1	0
%	0
of	0
women	0
and	0
were	0
dose	0
dependent	0
above	0
the	0
20	0
-	0
mg	0
dose	0
.	0

Myopathy	3
,	0
defined	0
as	0
muscle	0
symptoms	0
with	0
creatine	1
kinase	0
elevations	0
greater	0
than	0
10	0
times	0
the	0
upper	0
limit	0
of	0
normal	0
,	0
was	0
rare	0
and	0
associated	0
with	0
the	0
highest	0
recommended	0
daily	0
dose	0
of	0
lovastatin	1
(	0
80	0
mg	0
)	0
.	0

Estrogen	0
-	0
replacement	0
therapy	0
appeared	0
to	0
have	0
no	0
effect	0
on	0
either	0
the	0
efficacy	0
or	0
safety	0
profile	0
of	0
lovastatin	1
.	0

C0NCLUSI0N	0
:	0
Lovastatin	1
is	0
highly	0
effective	0
and	0
generally	0
well	0
tolerated	0
as	0
therapy	0
for	0
primary	0
hypercholesterolemia	3
in	0
women	0
.	0

Tetany	3
and	0
rhabdomyolysis	3
due	0
to	0
surreptitious	0
furosemide	1
-	0
-	0
importance	0
of	0
magnesium	1
supplementation	0
.	0

Diuretics	0
may	0
induce	0
hypokalemia	3
,	0
hypocalcemia	3
and	0
hypomagnesemia	3
.	0

While	0
severe	0
hypokalemia	3
may	0
cause	0
muscle	3
weakness	4
,	0
severe	0
hypomagnesemia	3
is	0
associated	0
with	0
muscle	3
spasms	4
and	0
tetany	3
which	0
cannot	0
be	0
corrected	0
by	0
potassium	1
and	0
calcium	1
supplementation	0
alone	0
(	0
1	0
,	0
2	0
)	0
.	0

Surreptitious	0
diuretic	0
ingestion	0
has	0
been	0
described	0
,	0
mainly	0
in	0
women	0
who	0
are	0
concerned	0
that	0
they	0
are	0
obese	3
or	0
edematous	3
.	0

Symptomatic	0
hypokalemia	3
has	0
been	0
reported	0
in	0
such	0
patients	0
(	0
3	0
-	0
7	0
)	0
and	0
in	0
one	0
case	0
hypocalcemia	3
was	0
observed	0
(	0
8	0
)	0
,	0
but	0
the	0
effects	0
of	0
magnesium	1
depletion	0
were	0
not	0
noted	0
in	0
these	0
patients	0
.	0

Ciprofloxacin	1
-	0
induced	0
nephrotoxicity	3
in	0
patients	0
with	0
cancer	3
.	0

Nephrotoxicity	3
associated	0
with	0
ciprofloxacin	1
is	0
uncommon	0
.	0

Five	0
patients	0
with	0
cancer	3
who	0
developed	0
acute	3
renal	4
failure	4
that	0
followed	0
treatment	0
with	0
ciprofloxacin	1
are	0
described	0
and	0
an	0
additional	0
15	0
cases	0
reported	0
in	0
the	0
literature	0
are	0
reviewed	0
.	0

0ther	0
than	0
elevation	0
of	0
serum	0
creatinine	1
levels	0
,	0
characteristic	0
clinical	0
manifestations	0
and	0
abnormal	0
laboratory	0
findings	0
are	0
not	0
frequently	0
present	0
.	0

Allergic	0
interstitial	3
nephritis	4
is	0
believed	0
to	0
be	0
the	0
underlying	0
pathological	0
-	0
process	0
.	0

Definitive	0
diagnosis	0
requires	0
performance	0
of	0
renal	0
biopsy	0
,	0
although	0
this	0
is	0
not	0
always	0
feasible	0
.	0

An	0
improvement	0
in	0
renal	0
function	0
that	0
followed	0
the	0
discontinuation	0
of	0
the	0
offending	0
antibiotic	0
supports	0
the	0
presumptive	0
diagnosis	0
of	0
ciprofloxacin	1
-	0
induced	0
acute	3
renal	4
failure	4
.	0

Venous	3
complications	4
of	0
midazolam	1
versus	0
diazepam	1
.	0

Although	0
some	0
studies	0
have	0
suggested	0
fewer	0
venous	3
complications	4
are	0
associated	0
with	0
midazolam	1
than	0
with	0
diazepam	1
for	0
endoscopic	0
procedures	0
,	0
this	0
variable	0
has	0
not	0
been	0
well	0
documented	0
.	0

We	0
prospectively	0
evaluated	0
the	0
incidence	0
of	0
venous	3
complications	4
after	0
intravenous	0
injection	0
of	0
diazepam	1
or	0
midazolam	1
in	0
122	0
consecutive	0
patients	0
undergoing	0
colonoscopy	0
and	0
esophagogastroduodenoscopy	0
.	0

0verall	0
,	0
venous	3
complications	4
were	0
more	0
frequent	0
with	0
diazepam	1
(	0
22	0
of	0
62	0
patients	0
)	0
than	0
with	0
midazolam	1
(	0
4	0
of	0
60	0
patients	0
)	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
.	0

A	0
palpable	0
venous	0
cord	0
was	0
present	0
in	0
23	0
%	0
(	0
14	0
of	0
62	0
)	0
of	0
patients	0
in	0
the	0
diazepam	1
group	0
,	0
compared	0
with	0
2	0
%	0
(	0
1	0
of	0
60	0
patients	0
)	0
in	0
the	0
midazolam	1
group	0
(	0
p	0
<	0
0	0
.	0
002	0
)	0
.	0

Pain	3
at	0
the	0
injection	0
site	0
occurred	0
in	0
35	0
%	0
(	0
22	0
of	0
62	0
)	0
of	0
patients	0
in	0
the	0
diazepam	1
group	0
compared	0
with	0
7	0
%	0
(	0
4	0
of	0
60	0
patients	0
)	0
in	0
the	0
midazolam	1
group	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
.	0

Swelling	3
and	0
warmth	0
at	0
the	0
injection	0
site	0
were	0
not	0
significantly	0
different	0
between	0
the	0
two	0
groups	0
.	0

Smoking	0
,	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
drug	0
use	0
,	0
intravenous	0
catheter	0
site	0
,	0
dwell	0
time	0
of	0
the	0
needle	0
,	0
alcohol	1
use	0
,	0
and	0
pain	3
during	0
the	0
injection	0
had	0
no	0
effect	0
on	0
the	0
incidence	0
of	0
venous	3
complications	4
.	0

Clarithromycin	1
-	0
associated	0
visual	3
hallucinations	4
in	0
a	0
patient	0
with	0
chronic	3
renal	4
failure	4
on	0
continuous	0
ambulatory	0
peritoneal	0
dialysis	0
.	0

Visual	3
hallucinations	4
are	0
a	0
rare	0
event	0
in	0
chronic	3
renal	4
failure	4
and	0
not	0
related	0
to	0
uremia	3
per	0
se	0
.	0

Unreported	0
in	0
the	0
literature	0
is	0
visual	3
hallucinations	4
occurring	0
in	0
association	0
with	0
the	0
new	0
macrolide	1
antibiotic	0
,	0
clarithromycin	1
.	0

We	0
describe	0
such	0
a	0
case	0
in	0
a	0
patient	0
with	0
end	3
-	4
stage	4
renal	4
disease	4
(	0
ESRD	3
)	0
maintained	0
on	0
continuous	0
ambulatory	0
peritoneal	0
dialysis	0
(	0
CAPD	0
)	0
.	0

The	0
combination	0
of	0
a	0
relatively	0
high	0
dose	0
of	0
clarithromycin	1
in	0
face	0
of	0
chronic	3
renal	4
failure	4
in	0
a	0
functionally	0
anephric	0
patient	0
,	0
with	0
underlying	0
aluminum	1
intoxication	0
,	0
may	0
have	0
facilitated	0
the	0
appearance	0
of	0
this	0
neurotoxic	3
side	0
effect	0
.	0

It	0
is	0
important	0
to	0
understand	0
the	0
pharmacokinetics	0
of	0
medications	0
in	0
face	0
of	0
chronic	3
renal	4
failure	4
,	0
the	0
possibility	0
of	0
drug	0
interactions	0
,	0
and	0
how	0
these	0
factors	0
should	0
help	0
guide	0
medication	0
therapy	0
in	0
the	0
ESRD	3
patient	0
.	0

Changes	0
in	0
peroxisomes	0
in	0
preneoplastic	0
liver	0
and	0
hepatoma	3
of	0
mice	0
induced	0
by	0
alpha	1
-	2
benzene	2
hexachloride	2
.	0

Peroxisomes	0
in	0
hepatomas	3
and	0
hyperplastic	0
preneoplastic	0
liver	3
lesions	4
induced	0
in	0
mice	0
by	0
500	0
ppm	0
alpha	1
-	2
benzene	2
hexachloride	2
were	0
examined	0
histochemically	0
and	0
electron	0
microscopically	0
.	0

Although	0
most	0
of	0
the	0
hepatomas	3
were	0
well	0
-	0
differentiated	0
tumors	3
and	0
contained	0
a	0
considerable	0
number	0
of	0
peroxisomes	0
,	0
the	0
tumor	3
cells	0
did	0
not	0
respond	0
to	0
ethyl	1
-	2
alpha	2
-	2
p	2
-	2
chlorophenoxyisobutyrate	2
with	0
proliferation	0
of	0
peroxisomes	0
.	0

At	0
the	0
16th	0
week	0
of	0
carcinogen	0
feeding	0
,	0
hyperplastic	0
nodules	0
appeared	0
and	0
advanced	0
to	0
further	0
stages	0
.	0

A	0
majority	0
of	0
the	0
nodules	0
showed	0
a	0
considerable	0
number	0
of	0
peroxisomes	0
and	0
the	0
inductive	0
proliferation	0
of	0
peroxisomes	0
.	0

Within	0
the	0
nodules	0
,	0
foci	0
of	0
proliferation	0
of	0
the	0
cells	0
that	0
showed	0
no	0
inducibility	0
of	0
proliferation	0
of	0
peroxisomes	0
appeared	0
.	0

These	0
cells	0
proliferated	0
further	0
,	0
replacing	0
the	0
most	0
part	0
of	0
the	0
nodules	0
,	0
and	0
with	0
this	0
process	0
hepatomas	3
appeared	0
to	0
have	0
been	0
formed	0
.	0

No	0
abnormal	0
matrical	0
inclusions	0
of	0
peroxisomes	0
were	0
formed	0
in	0
the	0
cells	0
of	0
hyperplastic	0
nodules	0
by	0
ethyl	1
-	2
alpha	2
-	2
p	2
-	2
chlorophenoxyisobutyrate	2
unlike	0
in	0
the	0
case	0
of	0
rats	0
.	0

Contribution	0
of	0
the	0
sympathetic	0
nervous	0
system	0
to	0
salt	0
-	0
sensitivity	0
in	0
lifetime	0
captopril	1
-	0
treated	0
spontaneously	0
hypertensive	3
rats	0
.	0

0BJECTIVE	0
:	0
To	0
test	0
the	0
hypothesis	0
that	0
,	0
in	0
lifetime	0
captopril	1
-	0
treated	0
spontaneously	0
hypertensive	3
rats	0
(	0
SHR	0
)	0
,	0
the	0
sympathetic	0
nervous	0
system	0
contributes	0
importantly	0
to	0
the	0
hypertensive	3
effect	0
of	0
dietary	1
sodium	2
chloride	2
supplementation	0
.	0

METH0DS	0
:	0
Male	0
SHR	0
(	0
aged	0
6	0
weeks	0
)	0
that	0
had	0
been	0
treated	0
from	0
conception	0
onward	0
with	0
either	0
captopril	1
or	0
vehicle	0
remained	0
on	0
a	0
basal	0
sodium	1
chloride	2
diet	0
or	0
were	0
fed	0
a	0
high	0
sodium	1
chloride	2
diet	0
.	0

After	0
2	0
weeks	0
,	0
the	0
rats	0
were	0
subjected	0
to	0
ganglionic	0
blockade	0
and	0
2	0
days	0
later	0
,	0
an	0
infusion	0
of	0
clonidine	1
.	0

RESULTS	0
:	0
Lifetime	0
captopril	1
treatment	0
significantly	0
lowered	0
mean	0
arterial	0
pressure	0
in	0
both	0
groups	0
.	0

Intravenous	0
infusion	0
of	0
the	0
ganglionic	0
blocker	0
hexamethonium	1
resulted	0
in	0
a	0
rapid	0
decline	0
in	0
MAP	0
that	0
eliminated	0
the	0
dietary	1
sodium	2
chloride	2
-	0
induced	0
increase	3
in	4
MAP	4
in	0
both	0
groups	0
.	0

Infusion	0
of	0
the	0
central	0
nervous	0
system	0
alpha2	1
-	2
adrenergic	2
receptor	2
agonist	2
clonidine	1
also	0
resulted	0
in	0
a	0
greater	0
reduction	0
in	0
MAP	0
in	0
both	0
groups	0
of	0
SHR	0
that	0
were	0
fed	0
the	0
high	0
(	0
compared	0
with	0
the	0
basal	0
)	0
sodium	1
chloride	2
diet	0
.	0

C0NCLUSI0NS	0
:	0
In	0
both	0
lifetime	0
captopril	1
-	0
treated	0
and	0
control	0
SHR	0
,	0
the	0
sympathetic	0
nervous	0
system	0
contributes	0
to	0
the	0
pressor	0
effects	0
of	0
a	0
high	0
sodium	1
chloride	2
diet	0
.	0

Angioedema	3
associated	0
with	0
droperidol	1
administration	0
.	0

Angioedema	3
,	0
also	0
known	0
as	0
angioneurotic	3
edema	4
or	0
Quincke	3
'	4
s	4
disease	4
,	0
is	0
a	0
well	0
-	0
demarcated	0
,	0
localized	0
edema	3
involving	0
the	0
subcutaneous	0
tissues	0
that	0
may	0
cause	0
upper	3
-	4
airway	4
obstruction	4
.	0

We	0
report	0
the	0
case	0
of	0
a	0
previously	0
healthy	0
19	0
-	0
year	0
-	0
old	0
man	0
with	0
no	0
known	0
drug	3
allergies	4
in	0
whom	0
angioedema	3
with	0
significant	0
tongue	3
swelling	4
and	0
protrusion	0
developed	0
within	0
10	0
minutes	0
of	0
the	0
administration	0
of	0
a	0
single	0
IV	0
dose	0
of	0
droperidol	1
.	0

Late	0
cardiotoxicity	3
after	0
treatment	0
for	0
a	0
malignant	0
bone	3
tumor	4
.	0

Cardiac	0
function	0
was	0
assessed	0
in	0
long	0
-	0
term	0
survivors	0
of	0
malignant	0
bone	3
tumors	4
who	0
were	0
treated	0
according	0
to	0
Rosen	1
'	2
s	2
T5	2
or	2
T10	2
protocol	2
,	0
both	0
including	0
doxorubicin	1
.	0

Thirty	0
-	0
one	0
patients	0
,	0
age	0
10	0
-	0
45	0
years	0
(	0
median	0
age	0
17	0
.	0
8	0
years	0
)	0
were	0
evaluated	0
2	0
.	0
3	0
-	0
14	0
.	0
1	0
years	0
(	0
median	0
8	0
.	0
9	0
years	0
)	0
following	0
completion	0
of	0
treatment	0
.	0

Cumulative	0
doses	0
of	0
doxorubicin	1
were	0
225	0
-	0
550	0
mg	0
/	0
m2	0
(	0
median	0
dose	0
360	0
)	0
.	0

The	0
evaluation	0
consisted	0
of	0
a	0
history	0
,	0
physical	0
examination	0
,	0
electrocardiogram	0
(	0
ECG	0
)	0
,	0
signal	0
averaged	0
ECG	0
,	0
24	0
-	0
hour	0
ambulatory	0
ECG	0
,	0
echocardiography	0
and	0
radionuclide	0
angiography	0
.	0

Eighteen	0
of	0
31	0
(	0
58	0
%	0
)	0
patients	0
showed	0
cardiac	3
toxicity	4
,	0
defined	0
as	0
having	0
one	0
or	0
more	0
of	0
the	0
following	0
abnormalities	0
:	0
late	0
potentials	0
,	0
complex	0
ventricular	3
arrhythmias	4
,	0
left	0
ventricular	3
dilation	4
,	0
decreased	0
shortening	0
fraction	0
,	0
or	0
decreased	0
ejection	0
fraction	0
.	0

The	0
incidence	0
of	0
cardiac	3
abnormalities	4
increased	0
with	0
length	0
of	0
follow	0
-	0
up	0
(	0
P	0
<	0
or	0
=	0
.	0
05	0
)	0
.	0

No	0
correlation	0
could	0
be	0
demonstrated	0
between	0
cumulative	0
dose	0
of	0
doxorubicin	1
and	0
cardiac	0
status	0
,	0
except	0
for	0
heart	0
rate	0
variability	0
.	0

When	0
adjusted	0
to	0
body	0
surface	0
area	0
,	0
the	0
left	0
ventricular	0
posterior	0
wall	0
thickness	0
(	0
LVPW	0
index	0
)	0
was	0
decreased	0
in	0
all	0
patients	0
.	0

The	0
incidence	0
of	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
is	0
high	0
and	0
increases	0
with	0
follow	0
-	0
up	0
,	0
irrespective	0
of	0
cumulative	0
dose	0
.	0

Life	0
-	0
long	0
cardiac	0
follow	0
-	0
up	0
in	0
these	0
patients	0
is	0
warranted	0
.	0

The	0
results	0
of	0
our	0
study	0
suggest	0
that	0
heart	0
rate	0
variability	0
and	0
LVPW	0
index	0
could	0
be	0
sensitive	0
indicators	0
for	0
cardiotoxicity	3
.	0

Acute	0
blood	0
pressure	0
elevations	0
with	0
caffeine	1
in	0
men	0
with	0
borderline	0
systemic	0
hypertension	3
.	0

Whether	0
the	0
vasoconstrictive	0
actions	0
of	0
caffeine	1
are	0
enhanced	0
in	0
hypertensive	3
persons	0
has	0
not	0
been	0
demonstrated	0
.	0

Thus	0
,	0
caffeine	1
(	0
3	0
.	0
3	0
mg	0
/	0
kg	0
)	0
versus	0
placebo	0
was	0
tested	0
in	0
48	0
healthy	0
men	0
(	0
aged	0
20	0
to	0
35	0
years	0
)	0
selected	0
after	0
screening	0
on	0
2	0
separate	0
occasions	0
.	0

Borderline	0
hypertensive	3
men	0
(	0
n	0
=	0
24	0
)	0
were	0
selected	0
with	0
screening	0
systolic	0
blood	0
pressure	0
(	0
BP	0
)	0
of	0
140	0
to	0
160	0
mm	0
Hg	0
and	0
/	0
or	0
diastolic	0
BP	0
90	0
to	0
99	0
mm	0
Hg	0
.	0

Low	0
-	0
risk	0
controls	0
(	0
n	0
=	0
24	0
)	0
reported	0
no	0
parental	0
history	0
of	0
hypertension	3
and	0
had	0
screening	0
BP	0
<	0
130	0
/	0
85	0
mm	0
Hg	0
.	0

Participants	0
were	0
then	0
tested	0
on	0
2	0
occasions	0
after	0
12	0
-	0
hour	0
abstinence	0
from	0
caffeine	1
in	0
each	0
of	0
2	0
protocols	0
;	0
this	0
required	0
a	0
total	0
of	0
4	0
laboratory	0
visits	0
.	0

Caffeine	1
-	0
induced	0
changes	0
in	0
diastolic	0
BP	0
were	0
2	0
to	0
3	0
times	0
larger	0
in	0
borderline	0
subjects	0
than	0
in	0
controls	0
(	0
+	0
8	0
.	0
4	0
vs	0
+	0
3	0
.	0
8	0
mm	0
Hg	0
,	0
p	0
<	0
0	0
.	0
0001	0
)	0
,	0
and	0
were	0
attributable	0
to	0
larger	0
changes	0
in	0
impedance	0
-	0
derived	0
measures	0
of	0
systemic	0
vascular	0
resistance	0
(	0
+	0
135	0
vs	0
+	0
45	0
dynes	0
.	0
s	0
.	0
cm	0
-	0
5	0
,	0
p	0
<	0
0	0
.	0
004	0
)	0
.	0

These	0
findings	0
were	0
consistent	0
and	0
reached	0
significance	0
in	0
both	0
protocols	0
.	0

The	0
percentage	0
of	0
borderline	0
subjects	0
in	0
whom	0
diastolic	0
BP	0
changes	0
exceeded	0
the	0
median	0
control	0
response	0
was	0
96	0
%	0
.	0

Consequently	0
,	0
whereas	0
all	0
participants	0
exhibited	0
normotensive	0
levels	0
during	0
the	0
resting	0
predrug	0
baseline	0
,	0
33	0
%	0
of	0
borderline	0
subjects	0
achieved	0
hypertensive	3
BP	0
levels	0
after	0
caffeine	1
ingestion	0
.	0

Thus	0
,	0
in	0
borderline	0
hypertensive	3
men	0
,	0
exaggerated	0
responses	0
to	0
caffeine	1
were	0
:	0
selective	0
for	0
diastolic	0
BP	0
,	0
consistent	0
with	0
greater	0
vasoconstriction	0
,	0
replicated	0
in	0
2	0
protocols	0
,	0
and	0
representative	0
of	0
nearly	0
all	0
borderline	0
hypertensives	3
.	0

We	0
suspect	0
that	0
the	0
potential	0
for	0
caffeine	1
to	0
stabilize	0
high	0
resistance	0
states	0
in	0
susceptible	0
persons	0
suggests	0
that	0
its	0
use	0
may	0
facilitate	0
their	0
disease	0
progression	0
,	0
as	0
well	0
as	0
hinder	0
accurate	0
diagnosis	0
and	0
treatment	0
.	0

Absence	0
of	0
effect	0
of	0
sertraline	1
on	0
time	0
-	0
based	0
sensitization	0
of	0
cognitive	3
impairment	4
with	0
haloperidol	1
.	0

This	0
double	0
-	0
blind	0
,	0
randomized	0
,	0
placebo	0
-	0
controlled	0
study	0
evaluated	0
the	0
effects	0
of	0
haloperidol	1
alone	0
and	0
haloperidol	1
plus	0
sertraline	1
on	0
cognitive	0
and	0
psychomotor	0
function	0
in	0
24	0
healthy	0
male	0
subjects	0
.	0

METH0D	0
:	0
All	0
subjects	0
received	0
placebo	0
on	0
Day	0
1	0
and	0
haloperidol	1
2	0
mg	0
on	0
Days	0
2	0
and	0
25	0
.	0

From	0
Days	0
9	0
to	0
25	0
,	0
subjects	0
were	0
randomly	0
assigned	0
to	0
either	0
sertraline	1
(	0
12	0
subjects	0
)	0
or	0
placebo	0
(	0
12	0
subjects	0
)	0
;	0
the	0
sertraline	1
dose	0
was	0
titrated	0
from	0
50	0
to	0
200	0
mg	0
/	0
day	0
from	0
Days	0
9	0
to	0
16	0
,	0
and	0
remained	0
at	0
200	0
mg	0
/	0
day	0
for	0
the	0
final	0
10	0
days	0
of	0
the	0
drug	0
administration	0
period	0
.	0

Cognitive	0
function	0
testing	0
was	0
performed	0
before	0
dosing	0
and	0
over	0
a	0
24	0
-	0
hour	0
period	0
after	0
dosing	0
on	0
Days	0
1	0
,	0
2	0
,	0
and	0
25	0
.	0

RESULTS	0
:	0
Impairment	3
of	4
cognitive	4
function	4
was	0
observed	0
6	0
to	0
8	0
hours	0
after	0
administration	0
of	0
haloperidol	1
on	0
Day	0
2	0
but	0
was	0
not	0
evident	0
23	0
hours	0
after	0
dosing	0
.	0

When	0
single	0
-	0
dose	0
haloperidol	1
was	0
given	0
again	0
25	0
days	0
later	0
,	0
greater	0
impairment	0
with	0
earlier	0
onset	0
was	0
noted	0
in	0
several	0
tests	0
in	0
both	0
treatment	0
groups	0
,	0
suggesting	0
enhancement	0
of	0
this	0
effect	0
.	0

There	0
was	0
no	0
indication	0
that	0
sertraline	1
exacerbated	0
the	0
impairment	0
produced	0
by	0
haloperidol	1
since	0
an	0
equivalent	0
effect	0
also	0
occurred	0
in	0
the	0
placebo	0
group	0
.	0

Three	0
subjects	0
(	0
2	0
on	0
sertraline	1
and	0
1	0
on	0
placebo	0
)	0
withdrew	0
from	0
the	0
study	0
because	0
of	0
side	0
effects	0
.	0

Ten	0
subjects	0
in	0
each	0
group	0
reported	0
side	0
effects	0
related	0
to	0
treatment	0
.	0

The	0
side	0
effect	0
profiles	0
of	0
sertraline	1
and	0
of	0
placebo	0
were	0
similar	0
.	0

C0NCLUSI0N	0
:	0
Haloperidol	1
produced	0
a	0
clear	0
profile	0
of	0
cognitive	3
impairment	4
that	0
was	0
not	0
worsened	0
by	0
concomitant	0
sertraline	1
administration	0
.	0

Coexistence	0
of	0
cerebral	3
venous	4
sinus	4
and	4
internal	4
carotid	4
artery	4
thrombosis	4
associated	0
with	0
exogenous	0
sex	0
hormones	0
.	0

A	0
case	0
report	0
.	0

A	0
forty	0
-	0
six	0
year	0
-	0
old	0
premenopausal	0
woman	0
developed	0
headache	3
,	0
nausea	3
and	0
vomiting	3
,	0
left	0
hemiparesis	3
and	0
seizure	3
two	0
days	0
after	0
parenteral	0
use	0
of	0
progesterone	1
and	0
estradiol	1
.	0

Diabetes	3
mellitus	4
(	0
DM	3
)	0
was	0
found	0
during	0
admission	0
.	0

Computed	0
tomography	0
showed	0
a	0
hemorrhagic	3
infarct	4
in	0
the	0
right	0
frontal	0
lobe	0
and	0
increased	0
density	0
in	0
the	0
superior	0
sagittal	0
sinus	0
(	0
SSS	0
)	0
.	0

Left	0
carotid	0
angiography	0
found	0
occlusion	3
of	4
the	4
left	4
internal	4
carotid	4
artery	4
(	0
ICA	0
)	0
.	0

Right	0
carotid	0
angiograms	0
failed	0
to	0
show	0
the	0
SSS	0
and	0
inferior	0
sagittal	0
sinus	0
,	0
suggestive	0
of	0
venous	3
sinus	4
thrombosis	4
.	0

Coexistence	0
of	0
the	0
cerebral	3
artery	4
and	4
the	4
venous	4
sinus	4
occlusion	4
has	0
been	0
described	0
infrequently	0
.	0

In	0
this	0
case	0
,	0
the	0
authors	0
postulate	0
that	0
the	0
use	0
of	0
estradiol	1
and	0
progesterone	1
and	0
the	0
underlying	0
DM	3
increased	0
vascular	0
thrombogenicity	0
,	0
which	0
provided	0
a	0
common	0
denominator	0
for	0
thrombosis	3
of	4
both	4
the	4
ICA	4
and	4
the	4
venous	4
sinus	4
.	0

Chemotherapy	0
of	0
advanced	0
inoperable	0
non	3
-	4
small	4
cell	4
lung	4
cancer	4
with	0
paclitaxel	1
:	0
a	0
phase	0
II	0
trial	0
.	0

Paclitaxel	1
(	0
Taxol	1
;	0
Bristol	0
-	0
Myers	0
Squibb	0
Company	0
,	0
Princeton	0
,	0
NJ	0
)	0
has	0
demonstrated	0
significant	0
antineoplastic	0
activity	0
against	0
different	0
tumor	3
types	0
,	0
notably	0
ovarian	3
and	4
breast	4
carcinoma	4
.	0

Two	0
phase	0
II	0
trials	0
of	0
24	0
-	0
hour	0
paclitaxel	1
infusions	0
in	0
chemotherapy	0
-	0
naive	0
patients	0
with	0
stage	0
IIIB	0
or	0
IV	0
non	3
-	4
small	4
cell	4
lung	4
cancer	4
(	0
NSCLC	3
)	0
reported	0
response	0
rates	0
of	0
21	0
%	0
and	0
24	0
%	0
.	0

Leukopenia	3
was	0
dose	0
limiting	0
:	0
as	0
many	0
as	0
62	0
.	0
5	0
%	0
of	0
patients	0
experienced	0
grade	0
4	0
leukopenia	3
.	0

We	0
investigated	0
the	0
efficacy	0
and	0
toxicity	3
of	0
a	0
3	0
-	0
hour	0
paclitaxel	1
infusion	0
in	0
a	0
phase	0
II	0
trial	0
in	0
patients	0
with	0
inoperable	0
stage	0
IIIB	0
or	0
IV	0
NSCLC	3
.	0

The	0
58	0
patients	0
treated	0
(	0
41	0
men	0
and	0
17	0
women	0
)	0
had	0
a	0
median	0
age	0
of	0
59	0
years	0
(	0
age	0
range	0
,	0
25	0
to	0
75	0
)	0
and	0
a	0
performance	0
status	0
of	0
0	0
through	0
2	0
.	0

Most	0
patients	0
(	0
72	0
.	0
4	0
%	0
)	0
had	0
stage	0
IV	0
NSCLC	3
.	0

Paclitaxel	1
225	0
mg	0
/	0
m2	0
was	0
infused	0
over	0
3	0
hours	0
every	0
3	0
weeks	0
with	0
standard	0
prophylactic	0
premedication	0
.	0

0f	0
50	0
patients	0
evaluable	0
for	0
response	0
,	0
12	0
(	0
24	0
%	0
)	0
had	0
partial	0
remission	0
,	0
26	0
(	0
52	0
%	0
)	0
had	0
no	0
change	0
,	0
and	0
12	0
had	0
disease	0
progression	0
(	0
24	0
%	0
)	0
.	0

Hematologic	0
toxicities	3
were	0
mild	0
:	0
only	0
one	0
patient	0
(	0
2	0
%	0
)	0
developed	0
grade	0
3	0
or	0
4	0
neutropenia	3
,	0
while	0
29	0
%	0
had	0
grade	0
1	0
or	0
2	0
.	0

Grade	0
1	0
or	0
2	0
polyneuropathy	3
affected	0
56	0
%	0
of	0
patients	0
while	0
only	0
one	0
(	0
2	0
%	0
)	0
experienced	0
severe	0
polyneuropathy	3
.	0

Similarly	0
,	0
grade	0
1	0
or	0
2	0
myalgia	3
/	0
arthralgia	3
was	0
observed	0
in	0
63	0
.	0
2	0
%	0
of	0
patients	0
,	0
but	0
only	0
14	0
.	0
3	0
%	0
experienced	0
grade	0
3	0
or	0
4	0
.	0

Nausea	3
and	0
vomiting	3
were	0
infrequent	0
,	0
with	0
14	0
%	0
of	0
patients	0
experiencing	0
grade	0
1	0
or	0
2	0
and	0
only	0
2	0
%	0
experiencing	0
grade	0
3	0
or	0
4	0
.	0

Paclitaxel	1
is	0
thus	0
an	0
active	0
single	0
agent	0
in	0
this	0
patient	0
population	0
,	0
with	0
a	0
3	0
-	0
hour	0
infusion	0
proving	0
comparably	0
effective	0
to	0
a	0
24	0
-	0
hour	0
infusion	0
and	0
superior	0
in	0
terms	0
of	0
the	0
incidence	0
of	0
hematologic	0
and	0
nonhematologic	0
toxicity	3
.	0

Further	0
phase	0
II	0
studies	0
with	0
paclitaxel	1
combined	0
with	0
other	0
drugs	0
active	0
against	0
NSCLC	3
are	0
indicated	0
,	0
and	0
phase	0
III	0
studies	0
comparing	0
paclitaxel	1
with	0
standard	0
chemotherapy	0
remain	0
to	0
be	0
completed	0
.	0

Paclitaxel	1
combined	0
with	0
carboplatin	1
in	0
the	0
first	0
-	0
line	0
treatment	0
of	0
advanced	0
ovarian	3
cancer	4
.	0

In	0
a	0
phase	0
I	0
study	0
to	0
determine	0
the	0
maximum	0
tolerated	0
dose	0
of	0
paclitaxel	1
(	0
Taxol	1
;	0
Bristol	0
-	0
Myers	0
Squibb	0
Company	0
,	0
Princeton	0
,	0
NJ	0
)	0
given	0
as	0
a	0
3	0
-	0
hour	0
infusion	0
in	0
combination	0
with	0
carboplatin	1
administered	0
every	0
21	0
days	0
to	0
women	0
with	0
advanced	0
ovarian	3
cancer	4
,	0
paclitaxel	1
doses	0
were	0
escalated	0
as	0
follows	0
:	0
level	0
1	0
,	0
135	0
mg	0
/	0
m2	0
;	0
level	0
2	0
,	0
160	0
mg	0
/	0
m2	0
;	0
level	0
3	0
,	0
185	0
mg	0
/	0
m2	0
;	0
and	0
level	0
4	0
,	0
210	0
mg	0
/	0
m2	0
.	0

The	0
fixed	0
dose	0
of	0
carboplatin	1
at	0
levels	0
1	0
through	0
4	0
was	0
given	0
to	0
achieve	0
an	0
area	0
under	0
the	0
concentration	0
-	0
time	0
curve	0
(	0
AUC	0
)	0
of	0
5	0
using	0
the	0
Calvert	0
formula	0
.	0

In	0
levels	0
5	0
and	0
6	0
the	0
carboplatin	1
dose	0
was	0
targeted	0
at	0
AUCs	0
of	0
6	0
and	0
7	0
.	0
5	0
,	0
respectively	0
,	0
combined	0
with	0
a	0
fixed	0
paclitaxel	1
dose	0
of	0
185	0
mg	0
/	0
m2	0
.	0

To	0
date	0
,	0
30	0
previously	0
untreated	0
patients	0
,	0
all	0
with	0
a	0
good	0
performance	0
status	0
(	0
Eastern	0
Cooperative	0
0ncology	0
Group	0
0	0
to	0
2	0
)	0
have	0
been	0
entered	0
into	0
this	0
ongoing	0
study	0
.	0

The	0
dose	0
-	0
limiting	0
toxicity	3
of	0
the	0
combination	0
was	0
myelosuppression	3
(	0
leukopenia	3
,	0
granulocytopenia	3
,	0
and	0
thrombocytopenia	3
)	0
.	0

Neurotoxicity	3
was	0
largely	0
moderate	0
.	0

So	0
far	0
,	0
14	0
patients	0
are	0
evaluable	0
for	0
response	0
;	0
of	0
these	0
,	0
eight	0
(	0
57	0
%	0
)	0
showed	0
objective	0
(	0
complete	0
or	0
partial	0
)	0
response	0
and	0
disease	0
stabilized	0
in	0
six	0
patients	0
.	0

No	0
patient	0
had	0
disease	0
progression	0
.	0

We	0
conclude	0
that	0
the	0
combination	0
of	0
paclitaxel	1
185	0
mg	0
/	0
m2	0
administered	0
as	0
a	0
3	0
-	0
hour	0
infusion	0
followed	0
immediately	0
by	0
a	0
1	0
-	0
hour	0
infusion	0
of	0
carboplatin	1
at	0
an	0
AUC	0
of	0
6	0
can	0
be	0
administered	0
safely	0
in	0
a	0
21	0
-	0
day	0
schedule	0
in	0
the	0
outpatient	0
setting	0
.	0

The	0
recommended	0
dose	0
for	0
phase	0
III	0
studies	0
is	0
paclitaxel	1
185	0
mg	0
/	0
m2	0
and	0
carboplatin	1
AUC	0
6	0
.	0

Effects	0
of	0
acute	0
steroid	1
administration	0
on	0
ventilatory	0
and	0
peripheral	0
muscles	0
in	0
rats	0
.	0

0ccasional	0
case	0
reports	0
have	0
shown	0
that	0
acute	0
myopathy	3
may	0
occur	0
in	0
patients	0
treated	0
with	0
massive	0
doses	0
of	0
corticosteroids	1
.	0

The	0
mechanism	0
of	0
this	0
myopathy	3
is	0
poorly	0
understood	0
.	0

Therefore	0
,	0
60	0
male	0
rats	0
were	0
randomly	0
assigned	0
to	0
receive	0
daily	0
injection	0
of	0
saline	0
(	0
C	0
)	0
,	0
methylprednisolone	1
(	0
M	1
)	0
,	0
or	0
triamcinolone	1
(	0
T	1
)	0
80	0
mg	0
/	0
kg	0
/	0
d	0
for	0
5	0
d	0
.	0

Nutritional	0
intake	0
,	0
measured	0
daily	0
in	0
15	0
animals	0
,	0
showed	0
a	0
significant	0
reduction	3
of	4
food	4
intake	4
in	0
the	0
steroid	1
-	0
treated	0
groups	0
(	0
-	0
50	0
and	0
-	0
79	0
%	0
in	0
M	1
and	0
T	1
,	0
respectively	0
)	0
.	0

This	0
was	0
associated	0
with	0
a	0
similar	0
loss	3
in	4
body	4
weight	4
.	0

In	0
the	0
45	0
remaining	0
animals	0
,	0
diaphragm	0
contractility	0
and	0
histopathologic	0
features	0
of	0
several	0
muscles	0
were	0
studied	0
.	0

Weights	0
of	0
respiratory	0
and	0
peripheral	0
muscles	0
were	0
similarly	0
decreased	0
after	0
steroid	1
treatment	0
.	0

Maximal	0
twitches	0
of	0
the	0
diaphragm	0
were	0
lower	0
in	0
the	0
C	0
group	0
(	0
653	0
+	0
/	0
-	0
174	0
g	0
/	0
cm	0
(	0
2	0
)	0
)	0
than	0
in	0
the	0
M	1
group	0
(	0
837	0
+	0
/	0
-	0
171	0
g	0
/	0
cm	0
(	0
2	0
)	0
;	0
p	0
<	0
0	0
.	0
05	0
)	0
and	0
the	0
T	1
group	0
(	0
765	0
+	0
/	0
-	0
145	0
g	0
/	0
cm	0
(	0
2	0
)	0
,	0
NS	0
)	0
.	0

Half	0
-	0
relaxation	0
time	0
was	0
prolonged	0
in	0
both	0
steroid	1
groups	0
,	0
and	0
time	0
to	0
peak	0
tension	0
was	0
longer	0
with	0
M	1
,	0
whereas	0
tetanic	3
tensions	0
were	0
similar	0
.	0

Steroid	1
treatment	0
also	0
induced	0
a	0
leftward	0
shift	0
of	0
the	0
force	0
-	0
frequency	0
curve	0
at	0
25	0
and	0
50	0
Hz	0
when	0
compared	0
with	0
saline	0
treatment	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

ATPase	0
staining	0
of	0
the	0
diaphragm	0
,	0
scalenus	0
medius	0
,	0
and	0
gastrocnemius	0
showed	0
type	0
IIb	0
fiber	0
atrophy	3
in	0
the	0
steroid	1
groups	0
and	0
also	0
diaphragmatic	0
type	0
IIa	0
atrophy	3
with	0
T	1
,	0
whereas	0
histologic	0
examinations	0
revealed	0
a	0
normal	0
muscular	0
pattern	0
with	0
absence	0
of	0
necrosis	3
.	0

Finally	0
,	0
a	0
pair	0
-	0
fed	0
(	0
PF	0
)	0
study	0
,	0
performed	0
in	0
18	0
rats	0
(	0
C	0
,	0
T	1
,	0
and	0
PF	0
)	0
,	0
showed	0
that	0
muscle	3
atrophy	4
was	0
considerably	0
less	0
pronounced	0
in	0
PF	0
animals	0
than	0
in	0
T	1
-	0
treated	0
animals	0
.	0

We	0
conclude	0
that	0
(	0
1	0
)	0
short	0
-	0
term	0
treatment	0
with	0
massive	0
doses	0
of	0
steroids	1
induced	0
severe	0
respiratory	0
and	0
limb	0
muscle	0
wasting	0
;	0
(	0
2	0
)	0
both	0
types	0
of	0
steroids	1
induced	0
predominantly	0
type	0
IIb	0
atrophy	3
,	0
resulting	0
in	0
the	0
expected	0
alterations	0
in	0
diaphragm	0
contractile	0
properties	0
;	0
(	0
3	0
)	0
neither	0
steroid	1
caused	0
muscle	0
necrosis	3
;	0
(	0
4	0
)	0
type	0
IIb	0
atrophy	3
was	0
not	0
caused	0
by	0
acute	0
nutritional	0
deprivation	0
alone	0
.	0

Continuous	0
subcutaneous	0
administration	0
of	0
mesna	1
to	0
prevent	0
ifosfamide	1
-	0
induced	0
hemorrhagic	3
cystitis	4
.	0

Hemorrhagic	3
cystitis	4
is	0
a	0
major	0
potential	0
toxicity	3
of	0
ifosfamide	1
that	0
can	0
be	0
prevented	0
by	0
administering	0
mesna	1
along	0
with	0
the	0
cytotoxic	0
agent	0
.	0

Mesna	1
is	0
generally	0
administered	0
by	0
the	0
intravenous	0
route	0
,	0
although	0
experience	0
with	0
oral	0
delivery	0
of	0
the	0
drug	0
has	0
increased	0
.	0

The	0
continuous	0
subcutaneous	0
administration	0
of	0
mesna	1
has	0
the	0
advantage	0
of	0
not	0
requiring	0
intravenous	0
access	0
.	0

In	0
addition	0
,	0
subcutaneous	0
delivery	0
of	0
the	0
neutralizing	0
agent	0
will	0
not	0
be	0
associated	0
with	0
the	0
risk	0
of	0
inadequate	0
urinary	0
mesna	1
concentrations	0
,	0
such	0
as	0
in	0
a	0
patient	0
taking	0
oral	0
mesna	1
who	0
experiences	0
severe	0
ifosfamide	1
-	0
induced	0
emesis	3
and	0
is	0
unable	0
to	0
absorb	0
the	0
drug	0
.	0

Limited	0
clinical	0
experience	0
with	0
continuous	0
subcutaneous	0
mesna	1
administration	0
suggests	0
it	0
is	0
a	0
safe	0
,	0
practical	0
,	0
and	0
economic	0
method	0
of	0
drug	0
delivery	0
that	0
permits	0
ifosfamide	1
to	0
be	0
administered	0
successfully	0
in	0
the	0
outpatient	0
setting	0
.	0

Leg	3
and	4
back	4
pain	4
after	0
spinal	0
anaesthesia	0
involving	0
hyperbaric	0
5	0
%	0
lignocaine	1
.	0

Fifty	0
-	0
four	0
patients	0
,	0
aged	0
27	0
-	0
90	0
years	0
,	0
who	0
were	0
given	0
lignocaine	1
5	0
%	0
in	0
6	0
.	0
8	0
%	0
glucose	1
solution	0
for	0
spinal	0
anaesthesia	0
were	0
studied	0
.	0

Thirteen	0
of	0
these	0
patients	0
experienced	0
pain	3
in	4
the	4
legs	4
and	4
/	4
or	4
back	4
after	0
recovery	0
from	0
anaesthesia	0
.	0

The	0
patients	0
affected	0
were	0
younger	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
and	0
the	0
site	0
of	0
the	0
dural	0
puncture	0
was	0
higher	0
(	0
p	0
<	0
0	0
.	0
01	0
)	0
than	0
those	0
individuals	0
without	0
pain	3
.	0

Five	0
of	0
the	0
13	0
patients	0
(	0
38	0
%	0
)	0
with	0
pain	3
and	0
seven	0
of	0
the	0
41	0
patients	0
(	0
17	0
%	0
)	0
without	0
pain	3
admitted	0
to	0
a	0
high	0
alcohol	1
intake	0
,	0
which	0
might	0
be	0
a	0
contributing	0
factor	0
.	0

Leg	3
and	4
/	4
or	4
back	4
pain	4
is	0
associated	0
with	0
the	0
intrathecal	0
use	0
of	0
hyperbaric	0
5	0
%	0
lignocaine	1
.	0

The	0
use	0
of	0
serum	0
cholinesterase	0
in	0
succinylcholine	1
apnoea	3
.	0

Fifteen	0
patients	0
demonstrating	0
unexpected	0
prolonged	0
apnoea	3
lasting	0
several	0
hours	0
after	0
succinylcholine	1
have	0
been	0
treated	0
by	0
a	0
new	0
preparation	0
of	0
human	0
serum	0
cholinesterase	0
.	0

Adequate	0
spontaneous	0
respiration	0
was	0
re	0
-	0
established	0
in	0
an	0
average	0
period	0
of	0
ten	0
minutes	0
after	0
the	0
injection	0
.	0

In	0
12	0
patients	0
biochemical	0
genetic	0
examinations	0
confirmed	0
the	0
presence	0
of	0
an	0
atypical	0
serum	0
cholinesterase	0
.	0

In	0
three	0
patients	0
none	0
of	0
the	0
usual	0
variants	0
were	0
found	0
.	0

It	0
is	0
therefore	0
supposed	0
that	0
other	0
unknown	0
variants	0
of	0
serum	0
cholinesterase	0
exist	0
which	0
cannot	0
hydrolyze	0
succinylcholine	1
.	0

The	0
use	0
of	0
serum	0
cholinesterase	0
in	0
succinylcholine	1
apnoea	3
provided	0
considerable	0
relief	0
to	0
both	0
patient	0
and	0
anaesthetist	0
.	0

Increased	0
sulfation	0
and	0
decreased	0
7alpha	0
-	0
hydroxylation	0
of	0
deoxycholic	1
acid	2
in	0
ethinyl	1
estradiol	2
-	0
induced	0
cholestasis	3
in	0
rats	0
.	0

Deoxycholic	1
acid	2
conjugation	0
,	0
transport	0
capacity	0
,	0
and	0
metabolism	0
were	0
compared	0
in	0
control	0
and	0
ethinyl	1
estradiol	2
-	0
treated	0
rats	0
.	0

Control	0
rats	0
were	0
found	0
to	0
have	0
a	0
lower	0
capacity	0
to	0
transport	0
deoxycholic	1
acid	2
than	0
taurodeoxycholic	1
acid	2
,	0
and	0
both	0
were	0
decreased	0
by	0
ethinyl	1
estradiol	2
treatment	0
.	0

During	0
[	0
24	0
-	0
14C	0
]	0
sodium	1
deoxycholate	2
infusion	0
,	0
[	0
14C	0
]	0
biliary	0
bile	1
acid	2
secretion	0
increased	0
,	0
but	0
bile	0
flow	0
did	0
not	0
change	0
significantly	0
in	0
either	0
control	0
or	0
ethinyl	1
estradiol	2
-	0
treated	0
rats	0
.	0

Ethinyl	1
estradiol	2
-	0
treated	0
animals	0
excreted	0
significantly	0
less	0
14C	0
as	0
taurocholic	1
acid	2
than	0
did	0
control	0
animals	0
,	0
consistent	0
with	0
an	0
impairment	0
of	0
7alpha	0
-	0
hydroxylation	0
of	0
taurodeoxycholic	1
acid	2
.	0

Ethinyl	1
estradiol	2
treatment	0
did	0
not	0
impair	0
conjugation	0
of	0
deoxycholic	1
acid	2
,	0
but	0
did	0
result	0
in	0
an	0
increase	0
in	0
sulfation	0
of	0
taurodeoxycholic	1
acid	2
from	0
1	0
.	0
5	0
%	0
in	0
controls	0
to	0
nearly	0
4	0
.	0
0	0
%	0
(	0
P	0
less	0
than	0
0	0
.	0
01	0
)	0
.	0

These	0
results	0
are	0
consistent	0
with	0
the	0
hypothesis	0
that	0
the	0
rat	0
has	0
a	0
poorer	0
tolerance	0
for	0
deoxycholic	1
acid	2
than	0
do	0
certain	0
other	0
species	0
.	0

Furthermore	0
,	0
the	0
rat	0
converts	0
deoxycholic	1
acid	2
,	0
a	0
poor	0
choleretic	0
,	0
to	0
taurocholic	1
acid	2
,	0
a	0
good	0
choleretic	0
.	0

When	0
this	0
conversion	0
is	0
impaired	0
with	0
ethinyl	1
estradiol	2
treatment	0
,	0
sulfation	0
may	0
be	0
an	0
important	0
alternate	0
pathway	0
for	0
excretion	0
of	0
this	0
potentially	0
harmful	0
bile	1
acid	2
.	0

Influence	0
of	0
diet	0
free	0
of	0
NAD	1
-	0
precursors	0
on	0
acetaminophen	1
hepatotoxicity	3
in	0
mice	0
.	0

Recently	0
,	0
we	0
demonstrated	0
the	0
hepatoprotective	0
effects	0
of	0
nicotinic	1
acid	2
amide	2
,	0
a	0
selective	0
inhibitor	0
of	0
poly	1
(	2
ADP	2
-	2
ribose	2
)	2
polymerase	0
(	0
PARP	0
;	0
EC	0
2	0
.	0
4	0
.	0
2	0
.	0
30	0
)	0
on	0
mice	0
suffering	0
from	0
acetaminophen	1
(	0
AAP	1
)	0
-	0
hepatitis	3
,	0
suggesting	0
that	0
the	0
AAP	1
-	0
induced	0
liver	3
injury	4
involves	0
a	0
step	0
which	0
depends	0
on	0
adenoribosylation	0
.	0

The	0
present	0
study	0
investigates	0
the	0
effects	0
of	0
a	0
diet	0
free	0
of	0
precursors	0
of	0
NAD	1
,	0
the	0
substrate	0
on	0
which	0
PARP	0
acts	0
,	0
in	0
female	0
NMRI	0
mice	0
with	0
AAP	1
hepatitis	3
and	0
evaluates	0
the	0
influence	0
of	0
simultaneous	0
ethanol	1
consumption	0
in	0
these	0
animals	0
.	0

Liver	3
injuries	4
were	0
quantified	0
as	0
serum	0
activities	0
of	0
glutamate	1
-	0
oxaloacetate	1
transaminase	0
(	0
G0T	0
)	0
and	0
glutamate	1
-	0
pyruvate	1
transaminase	0
(	0
GPT	0
)	0
.	0

While	0
AAP	1
caused	0
a	0
117	0
-	0
fold	0
elevation	0
of	0
serum	0
transaminase	0
activities	0
in	0
mice	0
kept	0
on	0
a	0
standard	0
laboratory	0
diet	0
,	0
which	0
was	0
significantly	0
exacerbated	0
by	0
ethanol	1
and	0
inhibited	0
by	0
nicotinic	1
acid	2
amide	2
(	0
NAA	1
)	0
,	0
adverse	0
effects	0
were	0
noted	0
in	0
animals	0
fed	0
a	0
diet	0
free	0
of	0
precursors	0
of	0
NAD	1
.	0

In	0
these	0
animals	0
,	0
only	0
minor	0
increases	0
of	0
serum	0
transaminase	0
activities	0
were	0
measured	0
in	0
the	0
presence	0
of	0
AAP	1
,	0
and	0
unlike	0
the	0
exacerbation	0
caused	0
by	0
ethanol	1
in	0
mice	0
on	0
a	0
standard	0
diet	0
,	0
the	0
liver	3
damage	4
was	0
inhibited	0
by	0
50	0
%	0
by	0
ethanol	1
.	0

A	0
further	0
64	0
%	0
reduction	0
of	0
hepatitis	3
was	0
observed	0
,	0
when	0
NAA	1
was	0
given	0
to	0
ethanol	1
/	0
AAP	1
-	0
mice	0
.	0

0ur	0
results	0
provide	0
evidence	0
that	0
the	0
AAP	1
-	0
induced	0
hepatitis	3
and	0
its	0
exacerbation	0
by	0
ethanol	1
can	0
either	0
be	0
reduced	0
by	0
end	0
-	0
product	0
inhibition	0
of	0
PARP	0
by	0
NAA	1
or	0
by	0
dietary	0
depletion	0
of	0
the	0
enzyme	0
'	0
s	0
substrate	0
NAD	1
.	0

We	0
see	0
the	0
main	0
application	0
of	0
NAA	1
as	0
for	0
the	0
combinational	0
use	0
in	0
pharmaceutical	0
preparations	0
of	0
acetaminophen	1
in	0
order	0
to	0
avoid	0
hepatic	3
damage	4
in	0
patients	0
treated	0
with	0
this	0
widely	0
used	0
analgesic	0
.	0

Nightmares	0
and	0
hallucinations	3
after	0
long	0
-	0
term	0
intake	0
of	0
tramadol	1
combined	0
with	0
antidepressants	0
.	0

Tramadol	1
is	0
a	0
weak	0
opioid	0
with	0
effects	0
on	0
adrenergic	0
and	0
serotonergic	0
neurotransmission	0
that	0
is	0
used	0
to	0
treat	0
cancer	3
pain	3
and	0
chronic	0
non	0
malignant	0
pain	3
.	0

This	0
drug	0
was	0
initiated	0
in	0
association	0
with	0
paroxetine	1
and	0
dosulepine	1
hydrochloride	2
in	0
a	0
tetraparetic	3
patient	0
with	0
chronic	3
pain	4
.	0

Fifty	0
-	0
six	0
days	0
after	0
initiation	0
of	0
the	0
treatment	0
the	0
patient	0
presented	0
hallucinations	3
that	0
only	0
stopped	0
after	0
the	0
withdrawal	0
of	0
psycho	0
-	0
active	0
drugs	0
and	0
tramadol	1
.	0

The	0
case	0
report	0
questions	0
the	0
long	0
term	0
use	0
of	0
pain	3
killers	0
combined	0
with	0
psycho	0
-	0
active	0
drugs	0
in	0
chronic	0
non	0
malignant	0
pain	3
,	0
especially	0
if	0
pain	3
is	0
under	0
control	0
.	0

Effect	0
of	0
calcium	1
chloride	2
and	0
4	1
-	2
aminopyridine	2
therapy	0
on	0
desipramine	1
toxicity	3
in	0
rats	0
.	0

BACKGR0UND	0
:	0
Hypotension	3
is	0
a	0
major	0
contributor	0
to	0
mortality	0
in	0
tricyclic	0
antidepressant	0
overdose	3
.	0

Recent	0
data	0
suggest	0
that	0
tricyclic	0
antidepressants	0
inhibit	0
calcium	1
influx	0
in	0
some	0
tissues	0
.	0

This	0
study	0
addressed	0
the	0
potential	0
role	0
of	0
calcium	1
channel	0
blockade	0
in	0
tricyclic	0
antidepressant	0
-	0
induced	0
hypotension	3
.	0

METH0DS	0
:	0
Two	0
interventions	0
were	0
studied	0
that	0
have	0
been	0
shown	0
previously	0
to	0
improve	0
blood	0
pressure	0
with	0
calcium	1
channel	0
blocker	0
overdose	3
.	0

CaCl2	1
and	0
4	1
-	2
aminopyridine	2
.	0

Anesthetized	0
rats	0
received	0
the	0
tricyclic	0
antidepressant	0
desipramine	1
IP	0
to	0
produce	0
hypotension	3
,	0
QRS	0
prolongation	0
,	0
and	0
bradycardia	3
.	0

Fifteen	0
min	0
later	0
,	0
animals	0
received	0
CaCl2	1
,	0
NaHC03	1
,	0
or	0
saline	0
.	0

In	0
a	0
second	0
experiment	0
,	0
rats	0
received	0
tricyclic	0
antidepressant	0
desipramine	1
IP	0
followed	0
in	0
15	0
min	0
by	0
4	1
-	2
aminopyridine	2
or	0
saline	0
.	0

RESULTS	0
:	0
NaHC03	1
briefly	0
(	0
5	0
min	0
)	0
reversed	0
hypotension	3
and	0
QRS	0
prolongation	0
.	0

CaCl2	1
and	0
4	1
-	2
aminopyridine	2
failed	0
to	0
improve	0
blood	0
pressure	0
.	0

The	0
incidence	0
of	0
ventricular	3
arrhythmias	4
(	0
p	0
=	0
0	0
.	0
004	0
)	0
and	0
seizures	3
(	0
p	0
=	0
0	0
.	0
03	0
)	0
in	0
the	0
CaCl2	1
group	0
was	0
higher	0
than	0
the	0
other	0
groups	0
.	0

C0NCLUSI0N	0
:	0
The	0
administration	0
of	0
CaCl2	1
or	0
4	1
-	2
aminopyridine	2
did	0
not	0
reverse	0
tricyclic	0
antidepressant	0
-	0
induced	0
hypotension	3
in	0
rats	0
.	0

CaCl2	1
therapy	0
may	0
possibly	0
worsen	0
both	0
cardiovascular	3
and	4
central	4
nervous	4
system	4
toxicity	4
.	0

These	0
findings	0
do	0
not	0
support	0
a	0
role	0
for	0
calcium	1
channel	0
inhibition	0
in	0
the	0
pathogenesis	0
of	0
tricyclic	0
antidepressant	0
-	0
induced	0
hypotension	3
.	0

Valsartan	1
,	0
a	0
new	0
angiotensin	1
II	2
antagonist	0
for	0
the	0
treatment	0
of	0
essential	0
hypertension	3
:	0
a	0
comparative	0
study	0
of	0
the	0
efficacy	0
and	0
safety	0
against	0
amlodipine	1
.	0

0BJECTIVE	0
:	0
To	0
compare	0
the	0
antihypertensive	0
efficacy	0
of	0
a	0
new	0
angiotensin	1
II	2
antagonist	0
,	0
valsartan	1
,	0
with	0
a	0
reference	0
therapy	0
,	0
amlodipine	1
.	0

METH0DS	0
:	0
0ne	0
hundred	0
sixty	0
-	0
eight	0
adult	0
outpatients	0
with	0
mild	0
to	0
moderate	0
hypertension	3
were	0
randomly	0
allocated	0
in	0
double	0
-	0
blind	0
fashion	0
and	0
equal	0
number	0
to	0
receive	0
80	0
mg	0
valsartan	1
or	0
5	0
mg	0
amlodipine	1
for	0
12	0
weeks	0
.	0

After	0
8	0
weeks	0
of	0
therapy	0
,	0
in	0
patients	0
whose	0
blood	0
pressure	0
remained	0
uncontrolled	0
,	0
5	0
mg	0
amlodipine	1
was	0
added	0
to	0
the	0
initial	0
therapy	0
.	0

Patients	0
were	0
assessed	0
at	0
4	0
,	0
8	0
,	0
and	0
12	0
weeks	0
.	0

The	0
primary	0
efficacy	0
variable	0
was	0
change	0
from	0
baseline	0
in	0
mean	0
sitting	0
diastolic	0
blood	0
pressure	0
at	0
8	0
weeks	0
.	0

Secondary	0
variables	0
included	0
change	0
in	0
sitting	0
systolic	0
blood	0
pressure	0
and	0
responder	0
rates	0
.	0

RESULTS	0
:	0
Both	0
valsartan	1
and	0
amlodipine	1
were	0
effective	0
at	0
lowering	0
blood	0
pressure	0
at	0
4	0
,	0
8	0
,	0
and	0
12	0
weeks	0
.	0

Similar	0
decreases	0
were	0
observed	0
in	0
both	0
groups	0
,	0
with	0
no	0
statistically	0
significant	0
differences	0
between	0
the	0
groups	0
for	0
any	0
variable	0
analyzed	0
.	0

For	0
the	0
primary	0
variable	0
the	0
difference	0
was	0
0	0
.	0
5	0
mm	0
Hg	0
in	0
favor	0
of	0
valsartan	1
(	0
p	0
=	0
0	0
.	0
68	0
;	0
95	0
%	0
confidence	0
interval	0
,	0
-	0
2	0
.	0
7	0
to	0
1	0
.	0
7	0
)	0
.	0

Responder	0
rates	0
at	0
8	0
weeks	0
were	0
66	0
.	0
7	0
%	0
for	0
valsartan	1
and	0
60	0
.	0
2	0
%	0
for	0
amlodipine	1
(	0
p	0
=	0
0	0
.	0
39	0
)	0
.	0

Both	0
treatments	0
were	0
well	0
tolerated	0
.	0

The	0
incidence	0
of	0
drug	0
-	0
related	0
dependent	0
edema	3
was	0
somewhat	0
higher	0
in	0
the	0
amlodipine	1
group	0
,	0
particularly	0
at	0
a	0
dose	0
of	0
10	0
mg	0
per	0
day	0
(	0
2	0
.	0
4	0
%	0
for	0
80	0
mg	0
valsartan	1
;	0
3	0
.	0
6	0
%	0
for	0
5	0
mg	0
amlodipine	1
;	0
0	0
%	0
for	0
valsartan	1
plus	0
5	0
mg	0
amlodipine	1
;	0
14	0
.	0
3	0
%	0
for	0
10	0
mg	0
amlodipine	1
)	0
.	0

C0NCLUSI0NS	0
:	0
The	0
data	0
show	0
that	0
valsartan	1
is	0
at	0
least	0
as	0
effective	0
as	0
amlodipine	1
in	0
the	0
treatment	0
of	0
mild	0
to	0
moderate	0
hypertension	3
.	0

The	0
results	0
also	0
show	0
valsartan	1
to	0
be	0
well	0
tolerated	0
and	0
suggest	0
that	0
it	0
is	0
not	0
associated	0
with	0
side	0
effects	0
characteristic	0
of	0
this	0
comparator	0
class	0
,	0
dihydropyridine	1
calcium	1
antagonists	0
.	0

A	0
measure	0
of	0
pupillary	3
oscillation	4
as	0
a	0
marker	0
of	0
cocaine	1
-	0
induced	0
paranoia	3
.	0

Cocaine	1
-	0
induced	0
paranoia	3
(	0
CIP	3
)	0
remains	0
an	0
important	0
drug	0
-	0
induced	0
model	0
of	0
idiopathic	0
paranoia	3
for	0
which	0
no	0
psychophysiologic	0
marker	0
has	0
yet	0
emerged	0
.	0

Measures	0
of	0
pupillary	3
oscillation	4
were	0
able	0
to	0
significantly	0
distinguish	0
a	0
group	0
of	0
abstinent	0
crack	1
cocaine	2
abusers	0
endorsing	0
past	0
CIP	3
(	0
n	0
=	0
32	0
)	0
from	0
another	0
group	0
of	0
crack	1
addicts	0
who	0
denied	0
past	0
CIP	3
(	0
n	0
=	0
29	0
)	0
.	0

Serotonin	3
syndrome	4
from	0
venlafaxine	1
-	0
tranylcypromine	1
interaction	0
.	0

Excessive	0
stimulation	0
of	0
serotonin	1
5HT1A	0
receptors	0
causes	0
a	0
syndrome	0
of	0
serotonin	1
excess	0
that	0
consists	0
of	0
shivering	0
,	0
muscle	3
rigidity	4
,	0
salivation	3
,	0
confusion	3
,	0
agitation	3
and	0
hyperthermia	3
.	0

The	0
most	0
common	0
cause	0
of	0
this	0
syndrome	0
is	0
an	0
interaction	0
between	0
a	0
monoamine	0
oxidase	0
inhibitor	0
(	0
MA0I	0
)	0
and	0
a	0
specific	0
serotonin	1
reuptake	0
inhibitor	0
.	0

Venlafaxine	1
is	0
a	0
new	0
antidepressant	0
agent	0
that	0
inhibits	0
the	0
reuptake	0
of	0
serotonin	1
and	0
norepinephrine	1
.	0

We	0
report	0
a	0
venlafaxine	1
-	0
MA0I	0
interaction	0
that	0
resulted	0
in	0
the	0
serotonin	3
syndrome	4
in	0
a	0
23	0
-	0
y	0
-	0
old	0
male	0
who	0
was	0
taking	0
tranylcypromine	1
for	0
depression	3
.	0

He	0
had	0
been	0
well	0
until	0
the	0
morning	0
of	0
presentation	0
when	0
he	0
took	0
1	0
/	0
2	0
tab	0
of	0
venlafaxine	1
.	0

Within	0
2	0
h	0
he	0
became	0
confused	0
with	0
jerking	0
movements	0
of	0
his	0
extremities	0
,	0
tremors	3
and	0
rigidity	3
.	0

He	0
was	0
brought	0
directly	0
to	0
a	0
hospital	0
where	0
he	0
was	0
found	0
to	0
be	0
agitated	0
and	0
confused	0
with	0
shivering	0
,	0
myoclonic	3
jerks	4
,	0
rigidity	3
,	0
salivation	3
and	0
diaphoresis	0
.	0

His	0
pupils	0
were	0
7	0
mm	0
and	0
sluggishly	0
reactive	0
to	0
light	0
.	0

Vital	0
signs	0
were	0
:	0
blood	0
pressure	0
120	0
/	0
67	0
mm	0
Hg	0
,	0
heart	0
rate	0
127	0
/	0
min	0
,	0
respiratory	0
rate	0
28	0
/	0
min	0
,	0
and	0
temperature	0
97	0
F	0
.	0

After	0
180	0
mg	0
of	0
diazepam	1
i	0
.	0
v	0
.	0
he	0
remained	0
tremulous	0
with	0
muscle	3
rigidity	4
and	0
clenched	0
jaws	0
.	0

He	0
was	0
intubated	0
for	0
airway	0
protection	0
and	0
because	0
of	0
hypoventilation	3
,	0
and	0
was	0
paralyzed	3
to	0
control	0
muscle	3
rigidity	4
.	0

His	0
subsequent	0
course	0
was	0
remarkable	0
for	0
non	0
-	0
immune	0
thrombocytopenia	3
which	0
resolved	0
.	0

The	0
patient	0
'	0
s	0
maximal	0
temperature	0
was	0
101	0
.	0
2	0
F	0
and	0
his	0
CPK	0
remained	0
<	0
500	0
units	0
/	0
L	0
with	0
no	0
other	0
evidence	0
of	0
rhabdomyolysis	3
.	0

His	0
mental	0
status	0
normalized	0
and	0
he	0
was	0
transferred	0
to	0
a	0
psychiatry	0
ward	0
.	0

This	0
patient	0
survived	0
without	0
sequelae	0
due	0
to	0
the	0
aggressive	0
sedation	0
and	0
neuromuscular	0
paralysis	3
.	0

Cyclophosphamide	1
associated	0
bladder	3
cancer	4
-	0
-	0
a	0
highly	0
aggressive	0
disease	0
:	0
analysis	0
of	0
12	0
cases	0
.	0

PURP0SE	0
:	0
We	0
gained	0
knowledge	0
of	0
the	0
etiology	0
,	0
treatment	0
and	0
prevention	0
of	0
cyclophosphamide	1
associated	0
urothelial	3
cancer	4
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
The	0
medical	0
records	0
of	0
6	0
men	0
and	0
6	0
women	0
(	0
mean	0
age	0
55	0
years	0
)	0
with	0
cyclophosphamide	1
associated	0
bladder	3
cancer	4
were	0
reviewed	0
.	0

RESULTS	0
:	0
All	0
tumors	3
were	0
grade	0
3	0
or	0
4	0
transitional	0
cell	0
carcinoma	3
.	0

0f	0
the	0
5	0
patients	0
initially	0
treated	0
with	0
endoscopic	0
resection	0
alone	0
only	0
1	0
is	0
alive	0
without	0
disease	0
.	0

0f	0
the	0
6	0
patients	0
who	0
underwent	0
early	0
cystectomy	0
4	0
were	0
alive	0
at	0
24	0
to	0
111	0
months	0
.	0

The	0
remaining	0
patient	0
with	0
extensive	0
cancer	3
underwent	0
partial	0
cystectomy	0
for	0
palliation	0
and	0
died	0
3	0
months	0
later	0
.	0

C0NCLUSI0NS	0
:	0
Cyclophosphamide	1
associated	0
bladder	3
tumor	4
is	0
an	0
aggressive	0
disease	0
.	0

However	0
,	0
long	0
-	0
term	0
survival	0
is	0
possible	0
when	0
radical	0
cystectomy	0
is	0
performed	0
for	0
bladder	3
tumors	4
with	0
any	0
sign	0
of	0
invasion	0
and	0
for	0
recurrent	0
high	0
grade	0
disease	0
,	0
even	0
when	0
noninvasive	0
.	0

A	0
phase	0
I	0
clinical	0
study	0
of	0
the	0
antipurine	1
antifolate	0
lometrexol	1
(	0
DDATHF	1
)	0
given	0
with	0
oral	0
folic	1
acid	2
.	0

Lometrexol	1
is	0
an	0
antifolate	0
which	0
inhibits	0
glycinamide	1
ribonucleotide	2
formyltransferase	0
(	0
GARFT	0
)	0
,	0
an	0
enzyme	0
essential	0
for	0
de	0
novo	0
purine	1
synthesis	0
.	0

Extensive	0
experimental	0
and	0
limited	0
clinical	0
data	0
have	0
shown	0
that	0
lometrexol	1
has	0
activity	0
against	0
tumours	3
which	0
are	0
refractory	0
to	0
other	0
drugs	0
,	0
notably	0
methotrexate	1
.	0

However	0
,	0
the	0
initial	0
clinical	0
development	0
of	0
lometrexol	1
was	0
curtailed	0
because	0
of	0
severe	0
and	0
cumulative	0
antiproliferative	0
toxicities	3
.	0

Preclinical	0
murine	0
studies	0
demonstrated	0
that	0
the	0
toxicity	3
of	0
lometrexol	1
can	0
be	0
prevented	0
by	0
low	0
dose	0
folic	1
acid	2
administration	0
,	0
i	0
.	0
e	0
.	0
for	0
7	0
days	0
prior	0
to	0
and	0
7	0
days	0
following	0
a	0
single	0
bolus	0
dose	0
.	0

This	0
observation	0
prompted	0
a	0
Phase	0
I	0
clinical	0
study	0
of	0
lometrexol	1
given	0
with	0
folic	1
acid	2
supplementation	0
which	0
has	0
confirmed	0
that	0
the	0
toxicity	3
of	0
lometrexol	1
can	0
be	0
markedly	0
reduced	0
by	0
folic	1
acid	2
supplementation	0
.	0

Thrombocytopenia	3
and	0
mucositis	3
were	0
the	0
major	0
toxicities	3
.	0

There	0
was	0
no	0
clear	0
relationship	0
between	0
clinical	0
toxicity	3
and	0
the	0
extent	0
of	0
plasma	0
folate	1
elevation	0
.	0

Associated	0
studies	0
demonstrated	0
that	0
lometrexol	1
plasma	0
pharmacokinetics	0
were	0
not	0
altered	0
by	0
folic	1
acid	2
administration	0
indicating	0
that	0
supplementation	0
is	0
unlikely	0
to	0
reduce	0
toxicity	3
by	0
enhancing	0
lometrexol	1
plasma	0
clearance	0
.	0

The	0
work	0
described	0
in	0
this	0
report	0
has	0
identified	0
for	0
the	0
first	0
time	0
a	0
clinically	0
acceptable	0
schedule	0
for	0
the	0
administration	0
of	0
a	0
GARFT	0
inhibitor	0
.	0

This	0
information	0
will	0
facilitate	0
the	0
future	0
evaluation	0
of	0
this	0
class	0
of	0
compounds	0
in	0
cancer	3
therapy	0
.	0

Fatal	0
excited	0
delirium	3
following	0
cocaine	1
use	0
:	0
epidemiologic	0
findings	0
provide	0
new	0
evidence	0
for	0
mechanisms	0
of	0
cocaine	1
toxicity	3
.	0

We	0
describe	0
an	0
outbreak	0
of	0
deaths	0
from	0
cocaine	1
-	0
induced	0
excited	0
delirium	3
(	0
EDDs	3
)	0
in	0
Dade	0
County	0
,	0
Florida	0
between	0
1979	0
and	0
1990	0
.	0

From	0
a	0
registry	0
of	0
all	0
cocaine	1
-	0
related	0
deaths	0
in	0
Dade	0
County	0
,	0
Florida	0
,	0
from	0
1969	0
-	0
1990	0
,	0
58	0
EDDs	3
were	0
compared	0
with	0
125	0
victims	0
of	0
accidental	0
cocaine	1
overdose	3
without	0
excited	0
delirium	3
.	0

Compared	0
with	0
controls	0
,	0
EDDs	3
were	0
more	0
frequently	0
black	0
,	0
male	0
,	0
and	0
younger	0
.	0

They	0
were	0
less	0
likely	0
to	0
have	0
a	0
low	0
body	0
mass	0
index	0
,	0
and	0
more	0
likely	0
to	0
have	0
died	0
in	0
police	0
custody	0
,	0
to	0
have	0
received	0
medical	0
treatment	0
immediately	0
before	0
death	0
,	0
to	0
have	0
survived	0
for	0
a	0
longer	0
period	0
,	0
to	0
have	0
developed	0
hyperthermia	3
,	0
and	0
to	0
have	0
died	0
in	0
summer	0
months	0
.	0

EDDs	3
had	0
concentrations	0
of	0
cocaine	1
and	0
benzoylecgonine	1
in	0
autopsy	0
blood	0
that	0
were	0
similar	0
to	0
those	0
for	0
controls	0
.	0

The	0
epidemiologic	0
findings	0
are	0
most	0
consistent	0
with	0
the	0
hypothesis	0
that	0
chronic	0
cocaine	1
use	0
disrupts	0
dopaminergic	0
function	0
and	0
,	0
when	0
coupled	0
with	0
recent	0
cocaine	1
use	0
,	0
may	0
precipitate	0
agitation	3
,	0
delirium	3
,	0
aberrant	0
thermoregulation	0
,	0
rhabdomyolysis	3
,	0
and	0
sudden	3
death	4
.	0

Pemoline	1
induced	0
acute	0
choreoathetosis	3
:	0
case	0
report	0
and	0
review	0
of	0
the	0
literature	0
.	0

BACKGR0UND	0
:	0
Pemoline	1
is	0
an	0
oxazolidine	1
derivative	0
that	0
is	0
structurally	0
different	0
from	0
amphetamines	1
and	0
used	0
in	0
the	0
treatment	0
of	0
attention	3
deficit	4
disorder	4
.	0

Pemoline	1
has	0
not	0
been	0
commonly	0
associated	0
in	0
the	0
literature	0
as	0
a	0
cause	0
of	0
acute	0
movement	3
disorders	4
.	0

The	0
following	0
case	0
describes	0
two	0
children	0
acutely	0
poisoned	0
with	0
pemoline	1
who	0
experienced	0
profound	0
choreoathetosis	3
.	0

CASE	0
REP0RT	0
:	0
Two	0
,	0
3	0
-	0
year	0
-	0
old	0
male	0
,	0
identical	0
twin	0
siblings	0
presented	0
to	0
the	0
emergency	0
department	0
after	0
found	0
playing	0
with	0
a	0
an	0
empty	0
bottle	0
of	0
pemoline	1
originally	0
containing	0
59	0
tablets	0
.	0

The	0
children	0
had	0
a	0
medical	0
history	0
significant	0
for	0
attention	3
deficit	4
disorder	4
previously	0
treated	0
with	0
methylphenidate	1
without	0
success	0
.	0

This	0
was	0
their	0
first	0
day	0
of	0
pemoline	1
therapy	0
.	0

The	0
choreoathetoid	3
movements	0
began	0
45	0
min	0
to	0
1	0
h	0
after	0
ingestion	0
.	0

The	0
children	0
gave	0
no	0
history	0
of	0
prior	0
movement	3
disorders	4
and	0
there	0
was	0
no	0
family	0
history	0
of	0
movement	3
disorders	4
.	0

The	0
children	0
received	0
gastrointestinal	0
decontamination	0
and	0
high	0
doses	0
of	0
intravenous	0
benzodiazepines	1
in	0
an	0
attempt	0
to	0
control	0
the	0
choreoathetoid	3
movements	0
.	0

Despite	0
treatment	0
,	0
the	0
children	0
continued	0
to	0
have	0
choreoathetosis	3
for	0
approximately	0
24	0
hours	0
.	0

Forty	0
-	0
eight	0
hours	0
after	0
admission	0
,	0
the	0
children	0
appeared	0
to	0
be	0
at	0
their	0
baseline	0
and	0
were	0
discharged	0
home	0
.	0

C0NCLUSI0N	0
:	0
Pemoline	1
associated	0
movement	3
disorder	4
has	0
been	0
rarely	0
reported	0
in	0
the	0
acute	0
toxicology	0
literature	0
.	0

The	0
possibility	0
of	0
choreoathetoid	3
movements	0
should	0
be	0
considered	0
in	0
patients	0
presenting	0
after	0
pemoline	1
overdose	3
.	0

Effect	0
of	0
myopic	0
excimer	0
laser	0
photorefractive	0
keratectomy	0
on	0
the	0
electrophysiologic	0
function	0
of	0
the	0
retina	0
and	0
optic	0
nerve	0
.	0

PURP0SE	0
:	0
To	0
assess	0
by	0
electrophysiologic	0
testing	0
the	0
effect	0
of	0
photorefractive	0
keratectomy	0
(	0
PRK	0
)	0
on	0
the	0
retina	0
and	0
optic	0
nerve	0
.	0

SETTING	0
:	0
Eye	0
Clinic	0
,	0
S	0
.	0

Salvatore	0
Hospital	0
,	0
L	0
'	0
Aquila	0
University	0
,	0
Italy	0
.	0

METH0DS	0
:	0
Standard	0
pattern	0
electroretinograms	0
(	0
P	0
-	0
ERGs	0
)	0
and	0
standard	0
pattern	0
visual	0
evoked	0
potentials	0
(	0
P	0
-	0
VEPs	0
)	0
were	0
done	0
in	0
25	0
eyes	0
of	0
25	0
patients	0
who	0
had	0
myopic	0
PRK	0
for	0
an	0
attempted	0
correction	0
between	0
5	0
.	0
00	0
and	0
15	0
.	0
00	0
diopters	0
(	0
D	0
)	0
(	0
mean	0
8	0
.	0
00	0
D	0
)	0
.	0

Testing	0
was	0
done	0
preoperatively	0
and	0
3	0
,	0
6	0
,	0
12	0
,	0
and	0
18	0
months	0
postoperatively	0
.	0

The	0
contralateral	0
eyes	0
served	0
as	0
controls	0
.	0

During	0
the	0
follow	0
-	0
up	0
,	0
3	0
patients	0
(	0
12	0
%	0
)	0
developed	0
steroid	1
-	0
induced	0
elevated	3
intraocular	4
pressure	4
(	0
I0P	0
)	0
that	0
resolved	0
after	0
corticosteroid	1
therapy	0
was	0
discontinued	0
.	0

RESULTS	0
:	0
No	0
statistically	0
significant	0
differences	0
were	0
seen	0
between	0
treated	0
and	0
control	0
eyes	0
nor	0
between	0
treated	0
eyes	0
preoperatively	0
and	0
postoperatively	0
.	0

C0NCLUSI0N	0
:	0
Myopic	0
excimer	0
laser	0
PRK	0
did	0
not	0
seem	0
to	0
affect	0
the	0
posterior	0
segment	0
.	0

The	0
transient	0
steroid	1
-	0
induced	0
I0P	3
rise	4
did	0
not	0
seem	0
to	0
cause	0
functional	0
impairment	0
.	0

Neutrophil	0
superoxide	1
and	0
hydrogen	1
peroxide	2
production	0
in	0
patients	0
with	0
acute	3
liver	4
failure	4
.	0

Defects	0
in	0
superoxide	1
and	0
hydrogen	1
peroxide	2
production	0
may	0
be	0
implicated	0
in	0
the	0
high	0
incidence	0
of	0
bacterial	3
infections	4
in	0
patients	0
with	0
acute	3
liver	4
failure	4
(	0
ALF	3
)	0
.	0

In	0
the	0
present	0
study	0
,	0
oxygen	1
radical	0
production	0
in	0
patients	0
with	0
ALF	3
due	0
to	0
paracetamol	1
overdose	3
was	0
compared	0
with	0
that	0
of	0
healthy	0
volunteers	0
.	0

Neutrophils	0
from	0
14	0
ALF	3
patients	0
were	0
stimulated	0
via	0
the	0
complement	0
receptors	0
using	0
zymosan	0
opsonized	0
with	0
ALF	3
or	0
control	0
serum	0
.	0

Superoxide	1
and	0
hydrogen	1
peroxide	2
production	0
by	0
ALF	3
neutrophils	0
stimulated	0
with	0
zymosan	0
opsonized	0
with	0
ALF	3
serum	0
was	0
significantly	0
reduced	0
compared	0
with	0
the	0
control	0
subjects	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

This	0
defect	0
persisted	0
when	0
zymosan	0
opsonized	0
by	0
control	0
serum	0
was	0
used	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

Superoxide	1
and	0
hydrogen	1
peroxide	2
production	0
in	0
neutrophils	0
stimulated	0
with	0
formyl	1
-	2
methionyl	2
-	2
leucyl	2
-	2
phenylalanine	2
(	0
fMLP	1
)	0
from	0
a	0
further	0
18	0
ALF	3
patients	0
was	0
unaffected	0
compared	0
with	0
control	0
neutrophils	0
.	0

Serum	0
C3	0
complement	0
levels	0
were	0
significantly	0
reduced	0
in	0
ALF	3
patients	0
compared	0
with	0
control	0
subjects	0
(	0
P	0
<	0
0	0
.	0
0005	0
)	0
.	0

These	0
results	0
demonstrate	0
a	0
neutrophil	0
defect	0
in	0
ALF	3
due	0
to	0
paracetamol	1
overdose	3
,	0
that	0
is	0
complement	0
dependent	0
but	0
independent	0
of	0
serum	0
complement	0
,	0
possibly	0
connected	0
to	0
the	0
complement	0
receptor	0
.	0

Cholesteryl	1
hemisuccinate	2
treatment	0
protects	0
rodents	0
from	0
the	0
toxic	0
effects	0
of	0
acetaminophen	1
,	0
adriamycin	1
,	0
carbon	1
tetrachloride	2
,	0
chloroform	1
and	0
galactosamine	1
.	0

In	0
addition	0
to	0
its	0
use	0
as	0
a	0
stabilizer	0
/	0
rigidifier	0
of	0
membranes	0
,	0
cholesteryl	1
hemisuccinate	2
,	0
tris	1
salt	2
(	0
CS	1
)	0
administration	0
has	0
also	0
been	0
shown	0
to	0
protect	0
rats	0
from	0
the	0
hepatotoxic	3
effects	0
of	0
carbon	1
tetrachloride	2
(	0
CCl4	1
)	0
.	0

To	0
further	0
our	0
understanding	0
of	0
the	0
mechanism	0
of	0
CS	1
cytoprotection	0
,	0
we	0
examined	0
in	0
rats	0
and	0
mice	0
the	0
protective	0
abilities	0
of	0
CS	1
and	0
the	0
non	0
-	0
hydrolyzable	0
ether	0
form	0
of	0
CS	1
,	0
gamma	1
-	2
cholesteryloxybutyric	2
acid	2
,	0
tris	1
salt	2
(	0
CSE	1
)	0
against	0
acetaminophen	1
-	0
,	0
adriamycin	1
-	0
,	0
carbon	1
tetrachloride	2
-	0
,	0
chloroform	1
-	0
and	0
galactosamine	1
-	0
induced	0
toxicity	3
.	0

The	0
results	0
of	0
these	0
studies	0
demonstrated	0
that	0
CS	1
-	0
mediated	0
protection	0
is	0
not	0
selective	0
for	0
a	0
particular	0
species	0
,	0
organ	0
system	0
or	0
toxic	0
chemical	0
.	0

A	0
24	0
-	0
h	0
pretreatment	0
of	0
both	0
rats	0
and	0
mice	0
with	0
a	0
single	0
dose	0
of	0
CS	1
(	0
100mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
,	0
resulted	0
in	0
significant	0
protection	0
against	0
the	0
hepatotoxic	3
effects	0
of	0
CCl4	1
,	0
CHCl3	1
,	0
acetaminophen	1
and	0
galactosamine	1
and	0
against	0
the	0
lethal	0
(	0
and	0
presumably	0
cardiotoxic	3
)	0
effect	0
of	0
adriamycin	1
administration	0
.	0

Maximal	0
CS	1
-	0
mediated	0
protection	0
was	0
observed	0
in	0
experimental	0
animals	0
pretreated	0
24	0
h	0
prior	0
to	0
the	0
toxic	0
insult	0
.	0

These	0
data	0
suggest	0
that	0
CS	1
intervenes	0
in	0
a	0
critical	0
cellular	0
event	0
that	0
is	0
an	0
important	0
common	0
pathway	0
to	0
toxic	0
cell	0
death	0
.	0

The	0
mechanism	0
of	0
CS	1
protection	0
does	0
not	0
appear	0
to	0
be	0
dependent	0
on	0
the	0
inhibition	0
of	0
chemical	0
bioactivation	0
to	0
a	0
toxic	0
reactive	0
intermediate	0
(	0
in	0
light	0
of	0
the	0
protection	0
observed	0
against	0
galactosamine	1
hepatotoxicity	3
)	0
.	0

However	0
,	0
based	0
on	0
the	0
data	0
presented	0
,	0
we	0
can	0
not	0
exclude	0
the	0
possibility	0
that	0
CS	1
administration	0
inhibits	0
chemical	0
bioactivation	0
.	0

0ur	0
findings	0
do	0
suggest	0
that	0
CS	1
-	0
mediated	0
protection	0
is	0
dependent	0
on	0
the	0
action	0
of	0
the	0
intact	0
anionic	0
CS	1
molecule	0
(	0
non	0
-	0
hydrolyzable	0
CSE	1
was	0
as	0
protective	0
as	0
CS	1
)	0
,	0
whose	0
mechanism	0
has	0
yet	0
to	0
be	0
defined	0
.	0

A	0
murine	0
model	0
of	0
adenomyosis	3
:	0
the	0
effects	0
of	0
hyperprolactinemia	3
induced	0
by	0
fluoxetine	1
hydrochloride	2
,	0
a	0
selective	0
serotonin	1
reuptake	0
inhibitor	0
,	0
on	0
adenomyosis	3
induction	0
in	0
Wistar	0
albino	0
rats	0
.	0

0BJECTIVE	0
:	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
investigate	0
whether	0
fluoxetine	1
given	0
to	0
castrated	0
and	0
noncastrated	0
rats	0
caused	0
hyperprolactinemia	3
and	0
its	0
effects	0
with	0
respect	0
to	0
adenomyosis	3
.	0

DESIGN	0
:	0
Fluoxetine	1
,	0
a	0
serotonin	1
reuptake	0
inhibitor	0
,	0
was	0
given	0
to	0
Wistar	0
Albino	0
rats	0
for	0
98	0
days	0
to	0
produce	0
hyperprolactinemia	3
.	0

The	0
drug	0
was	0
given	0
to	0
two	0
groups	0
consisting	0
of	0
castrated	0
and	0
noncastrated	0
rats	0
and	0
compared	0
to	0
two	0
groups	0
of	0
castrated	0
and	0
noncastrated	0
controls	0
.	0

Prolactin	0
levels	0
were	0
measured	0
and	0
the	0
uteri	0
of	0
the	0
rats	0
were	0
removed	0
for	0
histopathological	0
analysis	0
at	0
the	0
end	0
of	0
98	0
days	0
.	0

SETTING	0
:	0
Marmara	0
University	0
School	0
of	0
Medicine	0
,	0
Department	0
of	0
Histology	0
and	0
Embryology	0
,	0
Zeynep	0
Kamil	0
Women	0
and	0
Children	0
'	0
s	0
Hospital	0
.	0

MAIN	0
0UTC0ME	0
MEASURES	0
:	0
Serum	0
prolactin	0
levels	0
,	0
uterine	0
histopathology	0
.	0

RESULTS	0
:	0
The	0
prolactin	0
levels	0
of	0
castrated	0
and	0
noncastrated	0
groups	0
treated	0
with	0
fluoxetine	1
were	0
statistically	0
significantly	0
higher	0
when	0
compared	0
to	0
their	0
respective	0
control	0
groups	0
.	0

Histological	0
studies	0
revealed	0
11	0
cases	0
of	0
adenomyosis	3
,	0
all	0
within	0
the	0
noncastrated	0
group	0
receiving	0
fluoxetine	1
.	0

C0NCLUSI0N	0
:	0
It	0
was	0
suggested	0
that	0
high	0
serum	0
prolactin	0
levels	0
cause	0
degeneration	0
of	0
myometrial	0
cells	0
in	0
the	0
presence	0
of	0
ovarian	0
steroids	1
that	0
results	0
in	0
a	0
myometrial	0
invasion	0
by	0
endometrial	0
stroma	0
.	0

This	0
invasion	0
eventually	0
progresses	0
to	0
adenomyosis	3
.	0

Postinfarction	0
ventricular	3
septal	4
defect	4
associated	0
with	0
long	0
-	0
term	0
steroid	1
therapy	0
.	0

Two	0
cases	0
of	0
postinfarction	0
ventricular	3
septal	4
rupture	4
in	0
patients	0
on	0
long	0
-	0
term	0
steroid	1
therapy	0
are	0
presented	0
and	0
the	0
favourable	0
outcome	0
in	0
both	0
cases	0
described	0
.	0

A	0
possible	0
association	0
between	0
steroid	1
therapy	0
and	0
subsequent	0
postinfarction	0
septal	3
rupture	4
is	0
discussed	0
.	0

Neuroactive	0
steroids	1
protect	0
against	0
pilocarpine	1
-	0
and	0
kainic	1
acid	2
-	0
induced	0
limbic	0
seizures	3
and	0
status	3
epilepticus	4
in	0
mice	0
.	0

Several	0
structurally	0
related	0
metabolites	0
of	0
progesterone	1
(	0
3	1
alpha	2
-	2
hydroxy	2
pregnane	2
-	2
20	2
-	2
ones	2
)	0
and	0
deoxycorticosterone	1
(	0
3	1
alpha	2
-	2
hydroxy	2
pregnane	2
-	2
21	2
-	2
diol	2
-	2
20	2
-	2
ones	2
)	0
and	0
their	0
3	0
beta	0
-	0
epimers	0
were	0
evaluated	0
for	0
protective	0
activity	0
against	0
pilocarpine	1
-	0
,	0
kainic	1
acid	2
-	0
and	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
(	0
NMDA	1
)	0
-	0
induced	0
seizures	3
in	0
mice	0
.	0

Steroids	1
with	0
the	0
3	0
-	0
hydroxy	0
group	0
in	0
the	0
alpha	0
-	0
position	0
and	0
5	0
-	0
H	0
in	0
the	0
alpha	0
-	0
or	0
beta	0
-	0
configurations	0
were	0
highly	0
effective	0
in	0
protecting	0
against	0
pilocarpine	1
(	0
416	0
mg	0
/	0
kg	0
,	0
s	0
.	0
c	0
.	0
)	0
-	0
induced	0
limbic	0
motor	0
seizures	3
and	0
status	3
epilepticus	4
(	0
ED50	0
values	0
,	0
7	0
.	0
0	0
-	0
18	0
.	0
7	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
.	0

The	0
corresponding	0
epimers	0
with	0
the	0
3	0
-	0
hydroxy	0
group	0
in	0
the	0
beta	0
-	0
position	0
were	0
also	0
effective	0
but	0
less	0
potent	0
(	0
ED50	0
values	0
,	0
33	0
.	0
8	0
-	0
63	0
.	0
5	0
,	0
i	0
.	0
p	0
.	0
)	0
.	0

Although	0
the	0
neuroactive	0
steroids	1
were	0
considerably	0
less	0
potent	0
than	0
the	0
benzodiazepine	1
clonazepam	1
in	0
protecting	0
against	0
pilocarpine	1
seizures	3
,	0
steroids	1
with	0
the	0
5	0
alpha	0
,	0
3	0
alpha	0
-	0
configuration	0
had	0
comparable	0
or	0
higher	0
protective	0
index	0
values	0
(	0
TD50	0
for	0
motor	0
impairment	0
divided	0
by	0
ED50	0
for	0
seizure	3
protection	0
)	0
than	0
clonazepam	1
,	0
indicating	0
that	0
some	0
neuroactive	0
steroids	1
may	0
have	0
lower	0
relative	0
toxicity	3
.	0

Steroids	1
with	0
the	0
5	0
alpha	0
,	0
3	0
alpha	0
-	0
or	0
5	0
beta	0
,	0
3	0
alpha	0
-	0
configurations	0
also	0
produced	0
a	0
dose	0
-	0
dependent	0
delay	0
in	0
the	0
onset	0
of	0
limbic	0
seizures	3
induced	0
by	0
kainic	1
acid	2
(	0
32	0
mg	0
/	0
kg	0
,	0
s	0
.	0
c	0
.	0
)	0
,	0
but	0
did	0
not	0
completely	0
protect	0
against	0
the	0
seizures	3
.	0

However	0
,	0
when	0
a	0
second	0
dose	0
of	0
the	0
steroid	1
was	0
administered	0
1	0
hr	0
after	0
the	0
first	0
dose	0
,	0
complete	0
protection	0
from	0
the	0
kainic	1
acid	2
-	0
induced	0
limbic	0
seizures	3
and	0
status	3
epilepticus	4
was	0
obtained	0
.	0

The	0
steroids	1
also	0
caused	0
a	0
dose	0
-	0
dependent	0
delay	0
in	0
NMDA	1
(	0
257	0
mg	0
/	0
kg	0
,	0
s	0
.	0
c	0
.	0
)	0
-	0
induced	0
lethality	0
,	0
but	0
did	0
not	0
completely	0
protect	0
against	0
NMDA	1
seizures	3
or	0
lethality	0
.	0

We	0
conclude	0
that	0
neuroactive	0
steroids	1
are	0
highly	0
effective	0
in	0
protecting	0
against	0
pilocarpine	1
-	0
and	0
kainic	1
acid	2
-	0
induced	0
seizures	3
and	0
status	3
epilepticus	4
in	0
mice	0
,	0
and	0
may	0
be	0
of	0
utility	0
in	0
the	0
treatment	0
of	0
some	0
forms	0
of	0
status	3
epilepticus	4
in	0
humans	0
.	0

Hepatic	0
and	0
extrahepatic	0
angiotensinogen	0
gene	0
expression	0
in	0
rats	0
with	0
acute	0
nephrotic	3
syndrome	4
.	0

Plasma	0
concentration	0
and	0
urine	0
excretion	0
of	0
the	0
renin	0
-	0
angiotensin	1
system	0
proteins	0
are	0
altered	0
in	0
rats	0
with	0
nephrotic	3
syndrome	4
(	0
NS	3
)	0
.	0

In	0
this	0
work	0
the	0
messenger	0
ribonucleic	0
acid	0
(	0
mRNA	0
)	0
levels	0
of	0
angiotensinogen	0
(	0
Ao	0
)	0
were	0
analyzed	0
with	0
the	0
slot	0
-	0
blot	0
hybridization	0
technique	0
in	0
liver	0
and	0
other	0
extrahepatic	0
tissues	0
:	0
kidney	0
,	0
heart	0
,	0
brain	0
,	0
and	0
adrenal	0
gland	0
from	0
control	0
,	0
nephrotic	3
,	0
and	0
pair	0
-	0
fed	0
(	0
PF	0
)	0
rats	0
.	0

NS	3
was	0
induced	0
by	0
a	0
single	0
injection	0
of	0
puromycin	1
amino	2
-	2
nucleoside	2
(	0
PAN	1
)	0
.	0

Although	0
a	0
great	0
urinary	0
excretion	0
and	0
half	0
-	0
normal	0
plasma	0
levels	0
of	0
Ao	0
were	0
observed	0
on	0
day	0
6	0
after	0
PAN	1
injection	0
,	0
when	0
NS	3
was	0
clearly	0
established	0
,	0
hepatic	0
Ao	0
mRNA	0
levels	0
did	0
not	0
change	0
.	0

Furthermore	0
,	0
the	0
Ao	0
mRNA	0
levels	0
did	0
not	0
change	0
in	0
any	0
of	0
the	0
extrahepatic	0
tissues	0
studied	0
on	0
day	0
6	0
,	0
nor	0
did	0
its	0
hepatic	0
levels	0
at	0
days	0
1	0
,	0
3	0
,	0
5	0
,	0
or	0
7	0
after	0
PAN	1
injection	0
.	0

These	0
data	0
suggest	0
that	0
the	0
hepatic	0
and	0
extrahepatic	0
Ao	0
mRNA	0
levels	0
are	0
unaltered	0
during	0
the	0
development	0
of	0
the	0
acute	0
NS	3
induced	0
by	0
PAN	1
.	0

Neuroleptic	3
malignant	4
syndrome	4
with	0
risperidone	1
.	0

Neuroleptic	3
malignant	4
syndrome	4
is	0
thought	0
to	0
be	0
a	0
result	0
of	0
dopamine	1
D2	0
receptor	0
blockade	0
in	0
the	0
striatum	0
of	0
the	0
basal	0
ganglia	0
.	0

Risperidone	1
,	0
a	0
benzisoxazole	1
derivative	0
antipsychotic	0
,	0
has	0
high	0
serotonin	1
5	0
-	0
HT2	0
receptor	0
blockade	0
and	0
dose	0
-	0
related	0
D2	0
receptor	0
blockade	0
.	0

The	0
high	0
ratio	0
is	0
believed	0
to	0
impart	0
the	0
low	0
frequency	0
of	0
extrapyramidal	3
symptoms	4
with	0
risperidone	1
at	0
low	0
dosages	0
.	0

With	0
this	0
low	0
frequency	0
of	0
extrapyramidal	3
symptoms	4
,	0
it	0
was	0
thought	0
the	0
frequency	0
of	0
neuroleptic	3
malignant	4
syndrome	4
might	0
also	0
be	0
lowered	0
.	0

A	0
73	0
-	0
year	0
-	0
old	0
woman	0
developed	0
neuroleptic	3
malignant	4
syndrome	4
after	0
monotherapy	0
with	0
risperidone	1
.	0

The	0
syndrome	0
reversed	0
after	0
discontinuing	0
risperidone	1
and	0
starting	0
treatment	0
with	0
dantrolene	1
and	0
bromocriptine	1
.	0

It	0
appears	0
that	0
the	0
protection	0
from	0
extrapyramidal	0
side	0
effects	0
observed	0
with	0
risperidone	1
does	0
not	0
ensure	0
protection	0
from	0
neuroleptic	3
malignant	4
syndrome	4
.	0

The	0
attenuating	0
effect	0
of	0
carteolol	1
hydrochloride	2
,	0
a	0
beta	0
-	0
adrenoceptor	0
antagonist	0
,	0
on	0
neuroleptic	0
-	0
induced	0
catalepsy	3
in	0
rats	0
.	0

It	0
is	0
known	0
that	0
beta	0
-	0
adrenoceptor	0
antagonists	0
are	0
effective	0
in	0
the	0
treatment	0
of	0
akathisia	3
,	0
one	0
of	0
the	0
extrapyramidal	0
side	0
effects	0
that	0
occur	0
during	0
neuroleptic	0
treatment	0
.	0

Neuroleptic	0
-	0
induced	0
catalepsy	3
,	0
a	0
model	0
of	0
neuroleptic	0
-	0
induced	0
extrapyramidal	0
side	0
effects	0
,	0
was	0
considered	0
suitable	0
as	0
a	0
model	0
for	0
predicting	0
neuroleptic	0
-	0
induced	0
akathisia	3
in	0
humans	0
,	0
although	0
neuroleptic	0
-	0
induced	0
catalepsy	3
was	0
not	0
considered	0
a	0
specific	0
test	0
for	0
neuroleptic	0
-	0
induced	0
akathisia	3
.	0

Therefore	0
,	0
the	0
effects	0
of	0
carteolol	1
,	0
a	0
beta	0
-	0
adrenoceptor	0
antagonist	0
,	0
on	0
haloperidol	1
-	0
induced	0
catalepsy	3
in	0
rats	0
were	0
behaviorally	0
studied	0
and	0
compared	0
with	0
those	0
of	0
propranolol	1
and	0
biperiden	1
,	0
a	0
muscarinic	0
receptor	0
antagonist	0
.	0

Carteolol	1
,	0
as	0
well	0
as	0
propranolol	1
and	0
biperiden	1
,	0
inhibited	0
the	0
haloperidol	1
-	0
induced	0
catalepsy	3
.	0

The	0
inhibitory	0
effect	0
of	0
carteolol	1
was	0
almost	0
comparable	0
to	0
that	0
of	0
propranolol	1
,	0
but	0
was	0
weaker	0
than	0
that	0
of	0
biperiden	1
.	0

Carteolol	1
did	0
not	0
evoke	0
postsynaptic	0
dopamine	1
receptor	0
-	0
stimulating	0
behavioral	0
signs	0
such	0
as	0
stereotypy	0
and	0
hyperlocomotion	3
in	0
rats	0
.	0

Carteolol	1
did	0
not	0
antagonize	0
the	0
inhibitory	0
effects	0
of	0
haloperidol	1
on	0
apomorphine	1
-	0
induced	0
stereotypy	0
and	0
locomotor	0
activity	0
in	0
rats	0
.	0

In	0
addition	0
,	0
carteolol	1
did	0
not	0
evoke	0
5	0
-	0
HT1A	0
receptor	0
-	0
stimulating	0
behavioral	0
signs	0
such	0
as	0
flat	0
body	0
posture	0
and	0
forepaw	0
treading	0
and	0
did	0
not	0
inhibit	0
5	1
-	2
hydroxytryptophan	2
-	0
induced	0
head	0
twitch	0
in	0
rats	0
.	0

Finally	0
,	0
carteolol	1
did	0
not	0
inhibit	0
physostigmine	1
-	0
induced	0
lethality	0
in	0
rats	0
.	0

These	0
results	0
strongly	0
suggest	0
that	0
carteolol	1
improves	0
haloperidol	1
-	0
induced	0
catalepsy	3
via	0
its	0
beta	0
-	0
adrenoceptor	0
antagonistic	0
activity	0
and	0
is	0
expected	0
to	0
be	0
effective	0
in	0
the	0
treatment	0
of	0
akathisia	3
without	0
attenuating	0
neuroleptic	0
-	0
induced	0
antipsychotic	0
effects	0
due	0
to	0
its	0
postsynaptic	0
dopamine	1
receptor	0
antagonistic	0
activity	0
.	0

Granulosa	3
cell	4
tumor	4
of	4
the	4
ovary	4
associated	0
with	0
antecedent	0
tamoxifen	1
use	0
.	0

BACKGR0UND	0
:	0
Increased	0
attention	0
has	0
been	0
focused	0
recently	0
on	0
the	0
estrogenic	0
effects	0
of	0
tamoxifen	1
.	0

Review	0
of	0
the	0
literature	0
reveals	0
an	0
association	0
between	0
tamoxifen	1
use	0
and	0
gynecologic	0
tumors	3
.	0

CASE	0
:	0
A	0
52	0
-	0
year	0
-	0
old	0
postmenopausal	0
woman	0
was	0
treated	0
with	0
tamoxifen	1
for	0
stage	0
II	0
estrogen	1
receptor	0
-	0
positive	0
breast	3
carcinoma	4
.	0

Her	0
aspartate	1
transaminase	0
and	0
alanine	1
transaminase	0
levels	0
increase	0
markedly	0
after	0
6	0
months	0
of	0
tamoxifen	1
use	0
.	0

After	0
an	0
additional	0
17	0
months	0
of	0
elevated	0
serum	0
transaminases	0
,	0
the	0
patient	0
was	0
found	0
to	0
have	0
a	0
stage	0
Ic	0
granulosa	3
cell	4
tumor	4
of	4
the	4
ovary	4
.	0

C0NCLUSI0N	0
:	0
Patients	0
with	0
tamoxifen	1
-	0
induced	0
liver	3
dysfunction	4
may	0
be	0
at	0
increased	0
risk	0
for	0
granulosa	3
cell	4
tumors	4
because	0
of	0
alterations	0
in	0
tamoxifen	1
metabolism	0
.	0

Lifetime	0
treatment	0
of	0
mice	0
with	0
azidothymidine	1
(	0
AZT	1
)	0
produces	0
myelodysplasia	3
.	0

AZT	1
has	0
induced	0
a	0
macrocytic	3
anemia	4
in	0
AIDS	3
patients	0
on	0
long	0
term	0
AZT	1
therapy	0
.	0

It	0
is	0
generally	0
assumed	0
that	0
DNA	0
elongation	0
is	0
stopped	0
by	0
the	0
insertion	0
of	0
AZT	1
into	0
the	0
chain	0
in	0
place	0
of	0
thymidine	1
thus	0
preventing	0
the	0
phosphate	1
hydroxyl	0
linkages	0
and	0
therefore	0
suppresses	0
hemopoietic	0
progenitor	0
cell	0
proliferation	0
in	0
an	0
early	0
stage	0
of	0
differentiation	0
.	0

CBA	0
/	0
Ca	0
male	0
mice	0
started	0
on	0
AZT	1
0	0
.	0
75	0
mg	0
/	0
ml	0
H20	0
at	0
84	0
days	0
of	0
age	0
and	0
kept	0
on	0
it	0
for	0
687	0
days	0
when	0
dosage	0
reduced	0
to	0
0	0
.	0
5	0
mg	0
/	0
ml	0
H20	0
for	0
a	0
group	0
,	0
another	0
group	0
removed	0
from	0
AZT	1
to	0
see	0
recovery	0
,	0
and	0
third	0
group	0
remained	0
on	0
0	0
.	0
75	0
mg	0
.	0

At	0
687	0
days	0
mice	0
that	0
had	0
been	0
on	0
0	0
.	0
75	0
mg	0
had	0
average	0
platelet	0
counts	0
of	0
2	0
.	0
5	0
x	0
10	0
(	0
6	0
)	0
.	0

Histological	0
examination	0
on	0
9	0
of	0
10	0
mice	0
with	0
such	0
thrombocytopenia	3
showed	0
changes	0
compatible	0
with	0
myelodysplastic	3
syndrome	4
(	0
MDS	3
)	0
.	0

A	0
variety	0
of	0
histological	0
patterns	0
was	0
observed	0
.	0

There	0
were	0
two	0
cases	0
of	0
hypocellular	0
myelodysplasia	3
,	0
two	0
cases	0
of	0
hypersegmented	0
myelodysplastic	3
granulocytosis	0
,	0
two	0
cases	0
of	0
hypercellular	0
marrow	0
with	0
abnormal	0
megakaryocytes	0
with	0
bizarre	0
nuclei	0
,	0
one	0
case	0
of	0
megakaryocytic	0
myelosis	0
associated	0
with	0
a	0
hyperplastic	3
marrow	4
,	0
dysmyelopoiesis	3
and	0
a	0
hypocellular	3
marrow	4
and	0
two	0
cases	0
of	0
myelodysplasia	3
with	0
dyserythropoiesis	3
,	0
hemosiderosis	3
and	0
a	0
hypocellular	3
marrow	4
.	0

Above	0
mentioned	0
AZT	1
incorporation	0
may	0
have	0
induced	0
an	0
ineffective	0
hemopoiesis	0
in	0
the	0
primitive	0
hemopoietic	0
progenitor	0
cells	0
,	0
which	0
is	0
known	0
to	0
be	0
seen	0
commonly	0
in	0
the	0
myelodysplastic	3
syndrome	4
.	0

Biphasic	0
response	0
of	0
the	0
SA	0
node	0
of	0
the	0
dog	0
heart	0
in	0
vivo	0
to	0
selective	0
administration	0
of	0
ketamine	1
.	0

Effect	0
of	0
ketamine	1
on	0
the	0
SA	0
node	0
of	0
the	0
dog	0
heart	0
was	0
studied	0
in	0
vivo	0
using	0
a	0
selective	0
perfusion	0
technique	0
of	0
the	0
SA	0
node	0
artery	0
.	0

Injections	0
of	0
ketamine	1
in	0
doses	0
from	0
100	0
microgram	0
to	0
3	0
mg	0
into	0
the	0
artery	0
produced	0
a	0
depression	3
of	0
the	0
SA	0
nodal	0
activity	0
by	0
a	0
direct	0
action	0
.	0

This	0
depression	3
was	0
followed	0
by	0
the	0
sudden	0
appearance	0
of	0
a	0
stimulatory	0
phase	0
.	0

Bilateral	0
vagotomy	0
and	0
sympathectomy	0
or	0
prior	0
administration	0
of	0
a	0
ganglion	0
blocker	0
failed	0
to	0
inhibit	0
the	0
occurrence	0
of	0
the	0
ketamine	1
-	0
induced	0
tachycardia	3
,	0
while	0
it	0
was	0
completely	0
abolished	0
in	0
the	0
reserpinized	0
dogs	0
or	0
by	0
a	0
prior	0
injection	0
of	0
a	0
beta	0
-	0
blocking	0
agent	0
into	0
the	0
SA	0
node	0
artery	0
.	0

This	0
may	0
indicate	0
that	0
an	0
activation	0
of	0
the	0
peripheral	0
adrenergic	0
mechanism	0
plays	0
an	0
important	0
role	0
in	0
the	0
induction	0
of	0
the	0
excitatory	0
effect	0
of	0
ketamine	1
injected	0
in	0
the	0
SA	0
node	0
artery	0
.	0

0ver	0
expression	0
of	0
vascular	0
endothelial	0
growth	0
factor	0
and	0
its	0
receptor	0
during	0
the	0
development	0
of	0
estrogen	1
-	0
induced	0
rat	0
pituitary	3
tumors	4
may	0
mediate	0
estrogen	1
-	0
initiated	0
tumor	3
angiogenesis	0
.	0

Estrogens	1
,	0
which	0
have	0
been	0
associated	0
with	0
several	0
types	0
of	0
human	0
and	0
animal	0
cancers	3
,	0
can	0
induce	0
tumor	3
angiogenesis	0
in	0
the	0
pituitary	0
of	0
Fischer	0
344	0
rats	0
.	0

The	0
mechanistic	0
details	0
of	0
tumor	3
angiogenesis	0
induction	0
,	0
during	0
estrogen	1
carcinogenesis	3
,	0
are	0
still	0
unknown	0
.	0

To	0
elucidate	0
the	0
role	0
of	0
estrogen	1
in	0
the	0
regulation	0
of	0
tumor	3
angiogenesis	0
in	0
the	0
pituitary	0
of	0
female	0
rats	0
,	0
the	0
density	0
of	0
blood	0
vessels	0
was	0
analysed	0
using	0
factor	0
VIII	0
related	0
antigen	0
(	0
FVIIIRAg	0
)	0
immunohistochemistry	0
and	0
the	0
expression	0
of	0
vascular	0
endothelial	0
growth	0
factor	0
/	0
vascular	0
permeability	0
factor	0
(	0
VEGF	0
/	0
VPF	0
)	0
was	0
examined	0
by	0
Western	0
blot	0
and	0
immunohistochemical	0
analysis	0
.	0

The	0
expression	0
of	0
VEGF	0
receptor	0
(	0
VEGFR	0
-	0
2	0
/	0
Flk	0
-	0
1	0
/	0
KDR	0
)	0
was	0
also	0
examined	0
by	0
immunohistochemistry	0
.	0

The	0
results	0
demonstrated	0
that	0
17beta	1
-	2
estradiol	2
(	0
E2	1
)	0
induces	0
neovascularization	0
,	0
as	0
well	0
as	0
the	0
growth	0
and	0
enlargement	0
of	0
blood	0
vessels	0
after	0
7	0
days	0
of	0
exposure	0
.	0

The	0
high	0
tumor	3
angiogenic	0
potential	0
was	0
associated	0
with	0
an	0
elevated	0
VEGF	0
/	0
VPF	0
protein	0
expression	0
in	0
the	0
E2	1
exposed	0
pituitary	0
of	0
ovariectomized	0
(	0
0VEX	0
)	0
rats	0
.	0

VEGF	0
/	0
VPF	0
and	0
FVIIIRAg	0
immunohistochemistry	0
and	0
endothelial	0
specific	0
lectin	0
(	0
UEA1	0
)	0
binding	0
studies	0
,	0
indicate	0
that	0
the	0
elevation	0
of	0
VEGF	0
protein	0
expression	0
initially	0
occurred	0
in	0
both	0
blood	0
vessels	0
and	0
non	0
-	0
endothelial	0
cells	0
.	0

After	0
15	0
days	0
of	0
E2	1
exposure	0
,	0
VEGF	0
/	0
VPF	0
protein	0
expression	0
,	0
in	0
the	0
non	0
-	0
endothelial	0
cell	0
population	0
,	0
sharply	0
declined	0
and	0
was	0
restricted	0
to	0
the	0
blood	0
vessels	0
.	0

The	0
function	0
of	0
non	0
-	0
endothelial	0
-	0
derived	0
VEGF	0
is	0
not	0
clear	0
.	0

Furthermore	0
,	0
immunohistochemical	0
studies	0
demonstrated	0
that	0
VEGFR	0
-	0
2	0
(	0
flk	0
-	0
1	0
/	0
KDR	0
)	0
,	0
expression	0
was	0
elevated	0
significantly	0
in	0
the	0
endothelial	0
cells	0
of	0
microblood	0
vessels	0
after	0
7	0
days	0
of	0
E2	1
exposure	0
.	0

These	0
findings	0
suggest	0
that	0
over	0
expression	0
of	0
VEGF	0
and	0
its	0
receptor	0
(	0
VEGFR	0
-	0
2	0
)	0
may	0
play	0
an	0
important	0
role	0
in	0
the	0
initial	0
step	0
of	0
the	0
regulation	0
of	0
estrogen	1
induced	0
tumor	3
angiogenesis	0
in	0
the	0
rat	0
pituitary	0
.	0

Persistent	0
nephrogenic	3
diabetes	4
insipidus	4
following	0
lithium	1
therapy	0
.	0

We	0
report	0
the	0
case	0
of	0
a	0
patient	0
who	0
developed	0
severe	0
hypernatraemic	0
dehydration	3
following	0
a	0
head	3
injury	4
.	0

Ten	0
years	0
previously	0
he	0
had	0
been	0
diagnosed	0
to	0
have	0
lithium	1
-	0
induced	0
nephrogenic	3
diabetes	4
insipidus	4
,	0
and	0
lithium	1
therapy	0
had	0
been	0
discontinued	0
.	0

He	0
remained	0
thirsty	0
and	0
polyuric	3
despite	0
cessation	0
of	0
lithium	1
and	0
investigations	0
on	0
admission	0
showed	0
him	0
to	0
have	0
normal	0
osmoregulated	0
thirst	0
and	0
vasopressin	1
secretion	0
,	0
with	0
clear	0
evidence	0
of	0
nephrogenic	3
diabetes	4
insipidus	4
.	0

Lithium	1
induced	0
nephrogenic	3
diabetes	4
insipidus	4
is	0
considered	0
to	0
be	0
reversible	0
on	0
cessation	0
of	0
therapy	0
but	0
polyuria	3
persisted	0
in	0
this	0
patient	0
for	0
ten	0
years	0
after	0
lithium	1
was	0
stopped	0
.	0

We	0
discuss	0
the	0
possible	0
renal	0
mechanisms	0
and	0
the	0
implications	0
for	0
management	0
of	0
patients	0
with	0
lithium	1
-	0
induced	0
nephrogenic	3
diabetes	4
insipidus	4
.	0

Effects	0
of	0
NIK	1
-	2
247	2
on	0
cholinesterase	0
and	0
scopolamine	1
-	0
induced	0
amnesia	3
.	0

The	0
effects	0
of	0
NIK	1
-	2
247	2
on	0
cholinesterase	0
,	0
scopolamine	1
-	0
induced	0
amnesia	3
and	0
spontaneous	0
movement	0
were	0
examined	0
and	0
compared	0
with	0
those	0
of	0
the	0
well	0
-	0
known	0
cholinesterase	0
inhibitors	0
tacrine	1
and	0
E	1
-	2
2020	2
.	0

NIK	1
-	2
247	2
,	0
tacrine	1
and	0
E	1
-	2
2020	2
all	0
strongly	0
inhibited	0
acetylcholinesterase	0
(	0
AChE	0
)	0
in	0
human	0
red	0
blood	0
cells	0
(	0
IC50s	0
=	0
1	0
.	0
0	0
x	0
10	0
(	0
-	0
6	0
)	0
,	0
2	0
.	0
9	0
x	0
10	0
(	0
-	0
7	0
)	0
and	0
3	0
.	0
7	0
x	0
10	0
(	0
-	0
8	0
)	0
M	0
,	0
respectively	0
)	0
.	0

In	0
addition	0
,	0
NIK	1
-	2
247	2
and	0
tacrine	1
,	0
but	0
not	0
E	1
-	2
2020	2
,	0
strongly	0
inhibited	0
butyrylcholinestrase	0
(	0
BuChE	0
)	0
in	0
human	0
serum	0
.	0

All	0
three	0
drugs	0
produced	0
mixed	0
inhibition	0
of	0
AChE	0
activity	0
.	0

Moreover	0
,	0
the	0
inhibitory	0
effect	0
of	0
NIK	1
-	2
247	2
on	0
AChE	0
was	0
reversible	0
.	0

All	0
compounds	0
at	0
0	0
.	0
1	0
-	0
1	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
significantly	0
improved	0
the	0
amnesia	3
induced	0
by	0
scopolamine	1
(	0
0	0
.	0
5	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
in	0
rats	0
performing	0
a	0
passive	0
avoidance	0
task	0
.	0

The	0
three	0
compounds	0
at	0
1	0
and	0
3	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
did	0
not	0
significantly	0
decrease	0
spontaneous	0
movement	0
by	0
rats	0
.	0

These	0
findings	0
suggest	0
that	0
NIK	1
-	2
247	2
at	0
a	0
low	0
dose	0
(	0
0	0
.	0
1	0
-	0
1	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
)	0
improves	0
scopolamine	1
-	0
induced	0
amnesia	3
but	0
does	0
not	0
affect	0
spontaneous	0
movement	0
.	0

The	0
findings	0
suggest	0
that	0
NIK	1
-	2
247	2
may	0
be	0
a	0
useful	0
drug	0
for	0
the	0
treatment	0
of	0
Alzheimer	3
'	4
s	4
disease	4
.	0

Potential	0
therapeutic	0
use	0
of	0
the	0
selective	0
dopamine	1
D1	0
receptor	0
agonist	0
,	0
A	1
-	2
86929	2
:	0
an	0
acute	0
study	0
in	0
parkinsonian	3
levodopa	1
-	0
primed	0
monkeys	0
.	0

The	0
clinical	0
utility	0
of	0
dopamine	1
(	0
DA	1
)	0
D1	0
receptor	0
agonists	0
in	0
the	0
treatment	0
of	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
is	0
still	0
unclear	0
.	0

The	0
therapeutic	0
use	0
of	0
selective	0
DA	1
D1	0
receptor	0
agonists	0
such	0
as	0
SKF	1
-	2
82958	2
(	0
6	1
-	2
chloro	2
-	2
7	2
,	2
8	2
-	2
dihydroxy	2
-	2
3	2
-	2
allyl	2
-	2
1	2
-	2
phenyl	2
-	2
2	2
,	2
3	2
,	2
4	2
,	2
5	2
-	2
tetrahydro	2
-	2
1H	2
-	2
3	2
-	2
benzaze	2
pine	2
hydrobromide	2
)	0
and	0
A	1
-	2
77636	2
(	0
[	1
1R	2
,	2
3S	2
]	2
3	2
-	2
[	2
1	2
'	2
-	2
admantyl	2
]	2
-	2
1	2
-	2
aminomethyl	2
-	2
3	2
,	2
4	2
-	2
dihydro	2
-	2
5	2
,	2
6	2
-	2
dihydroxy	2
-	2
1H	2
-	2
2	2
-	2
benzo	2
pyran	2
hydrochloride	2
)	0
seems	0
limited	0
because	0
of	0
their	0
duration	0
of	0
action	0
,	0
which	0
is	0
too	0
short	0
for	0
SKF	1
-	2
82958	2
(	0
<	0
1	0
hr	0
)	0
and	0
too	0
long	0
for	0
A	1
-	2
77636	2
(	0
>	0
20	0
hr	0
,	0
leading	0
to	0
behavioral	0
tolerance	0
)	0
.	0

We	0
therefore	0
conducted	0
the	0
present	0
acute	0
dose	0
-	0
response	0
study	0
in	0
four	0
1	1
-	2
methyl	2
-	2
4	2
-	2
phenyl	2
-	2
1	2
,	2
2	2
,	2
3	2
,	2
6	2
-	2
tetrahydropyridine	2
(	0
MPTP	1
)	0
-	0
exposed	0
cynomolgus	0
monkeys	0
primed	0
to	0
exhibit	0
levodopa	1
-	0
induced	0
dyskinesias	3
to	0
evaluate	0
the	0
locomotor	0
and	0
dyskinetic	3
effects	0
on	0
challenge	0
with	0
four	0
doses	0
(	0
from	0
0	0
.	0
03	0
to	0
1	0
.	0
0	0
mg	0
/	0
kg	0
)	0
of	0
A	1
-	2
86929	2
(	0
[	1
-	2
]	2
-	2
[	2
5aR	2
,	2
11bS	2
]	2
-	2
4	2
,	2
5	2
,	2
5a	2
,	2
6	2
,	2
7	2
,	2
11b	2
-	2
hexahydro	2
-	2
2	2
-	2
propyl	2
-	2
3	2
-	2
thia	2
-	2
5	2
-	2
+	2
+	2
+	2
azacyclopent	2
-	2
1	2
-	2
ena	2
[	2
c	2
]	2
phenathrene	2
-	2
9	2
-	2
10	2
-	2
diol	2
)	0
,	0
a	0
selective	0
and	0
full	0
DA	1
D1	0
-	0
like	0
receptor	0
agonist	0
with	0
an	0
intermediate	0
duration	0
of	0
action	0
.	0

Levodopa	1
and	0
the	0
DA	1
D2	0
-	0
like	0
receptor	0
agonist	0
,	0
LY	1
-	2
171555	2
(	0
[	1
4aR	2
-	2
trans	2
]	2
-	2
4	2
,	2
4a	2
,	2
5	2
,	2
6	2
,	2
7	2
,	2
8	2
,	2
8a	2
,	2
9	2
-	2
o	2
-	2
dihydro	2
-	2
5n	2
-	2
propyl	2
-	2
2H	2
-	2
pyrazo	2
lo	2
-	2
3	2
-	2
4	2
-	2
quinoline	2
hydrochloride	2
)	0
were	0
also	0
used	0
for	0
comparison	0
.	0

Acute	0
administration	0
of	0
A	1
-	2
86929	2
was	0
as	0
efficacious	0
in	0
alleviating	0
MPTP	1
-	0
induced	0
parkinsonism	3
as	0
levodopa	1
and	0
LY	1
-	2
171555	2
,	0
but	0
was	0
less	0
likely	0
to	0
reproduce	0
the	0
levodopa	1
-	0
induced	0
dyskinesias	3
in	0
these	0
animals	0
than	0
with	0
either	0
LY	1
-	2
171555	2
or	0
subsequent	0
challenge	0
of	0
levodopa	1
.	0

Selective	0
stimulation	0
of	0
the	0
DA	1
D1	0
receptor	0
may	0
provide	0
better	0
integration	0
of	0
neural	0
inputs	0
transmitted	0
to	0
the	0
internal	0
segment	0
of	0
the	0
globus	0
pallidus	0
(	0
referred	0
to	0
as	0
the	0
basal	0
ganglia	0
output	0
)	0
compared	0
with	0
levodopa	1
and	0
selective	0
DA	1
D2	0
receptor	0
agonist	0
.	0

Potent	0
DA	1
D1	0
receptor	0
agents	0
with	0
an	0
intermediate	0
duration	0
of	0
efficacy	0
such	0
as	0
A	1
-	2
86929	2
(	0
approximately	0
4	0
hr	0
at	0
higher	0
doses	0
tested	0
)	0
are	0
potential	0
therapeutic	0
tools	0
in	0
PD	3
and	0
merit	0
further	0
attention	0
.	0

Neuropeptide	0
-	0
Y	0
immunoreactivity	0
in	0
the	0
pilocarpine	1
model	0
of	0
temporal	3
lobe	4
epilepsy	4
.	0

Neuropeptide	0
-	0
Y	0
(	0
NPY	0
)	0
is	0
expressed	0
by	0
granule	0
cells	0
and	0
mossy	0
fibres	0
of	0
the	0
hippocampal	0
dentate	0
gyrus	0
during	0
experimental	0
temporal	3
lobe	4
epilepsy	4
(	0
TLE	3
)	0
.	0

This	0
expression	0
may	0
represent	0
an	0
endogenous	0
damping	0
mechanism	0
since	0
NPY	0
has	0
been	0
shown	0
to	0
block	0
seizure	3
-	0
like	0
events	0
following	0
high	0
-	0
frequency	0
stimulation	0
in	0
hippocampal	0
slices	0
.	0

The	0
pilocarpine	1
(	0
PIL0	1
)	0
model	0
of	0
epilepsy	3
is	0
characterized	0
by	0
an	0
acute	0
period	0
of	0
status	3
epilepticus	4
followed	0
by	0
spontaneous	0
recurrent	0
seizures	3
and	0
related	0
brain	3
damage	4
.	0

We	0
report	0
peroxidase	0
-	0
antiperoxidase	0
immunostaining	0
for	0
NPY	0
in	0
several	0
brain	0
regions	0
in	0
this	0
model	0
.	0

PIL0	1
-	0
injected	0
animals	0
exhibited	0
NPY	0
immunoreactivity	0
in	0
the	0
region	0
of	0
the	0
mossy	0
fibre	0
terminals	0
,	0
in	0
the	0
dentate	0
gyrus	0
inner	0
molecular	0
layer	0
and	0
,	0
in	0
a	0
few	0
cases	0
,	0
within	0
presumed	0
granule	0
cells	0
.	0

NPY	0
immunoreactivity	0
was	0
also	0
dramatically	0
changed	0
in	0
the	0
entorhinal	0
cortex	0
,	0
amygdala	0
and	0
sensorimotor	0
areas	0
.	0

In	0
addition	0
,	0
PIL0	1
injected	0
animals	0
exhibited	0
a	0
reduction	0
in	0
the	0
number	0
of	0
NPY	0
-	0
immunoreactive	0
interneurons	0
compared	0
with	0
controls	0
.	0

The	0
results	0
demonstrate	0
that	0
changes	0
in	0
NPY	0
expression	0
,	0
including	0
expression	0
in	0
the	0
granule	0
cells	0
and	0
mossy	0
fibres	0
and	0
the	0
loss	0
of	0
vulnerable	0
NPY	0
neurons	0
,	0
are	0
present	0
in	0
the	0
PIL0	1
model	0
of	0
TLE	3
.	0

However	0
,	0
the	0
significance	0
of	0
this	0
changed	0
synthesis	0
of	0
NPY	0
remains	0
to	0
be	0
determined	0
.	0

Posteroventral	0
medial	0
pallidotomy	0
in	0
advanced	0
Parkinson	3
'	4
s	4
disease	4
.	0

BACKGR0UND	0
:	0
Posteroventral	0
medial	0
pallidotomy	0
sometimes	0
produces	0
striking	0
improvement	0
in	0
patients	0
with	0
advanced	0
Parkinson	3
'	4
s	4
disease	4
,	0
but	0
the	0
studies	0
to	0
date	0
have	0
involved	0
small	0
numbers	0
of	0
patients	0
and	0
short	0
-	0
term	0
follow	0
-	0
up	0
.	0

METH0DS	0
:	0
Forty	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
underwent	0
serial	0
,	0
detailed	0
assessments	0
both	0
after	0
drug	0
withdrawal	0
(	0
"	0
off	0
"	0
period	0
)	0
and	0
while	0
taking	0
their	0
optimal	0
medical	0
regimens	0
(	0
"	0
on	0
"	0
period	0
)	0
.	0

All	0
patients	0
were	0
examined	0
preoperatively	0
and	0
39	0
were	0
examined	0
at	0
six	0
months	0
;	0
27	0
of	0
the	0
patients	0
were	0
also	0
examined	0
at	0
one	0
year	0
,	0
and	0
11	0
at	0
two	0
years	0
.	0

RESULTS	0
:	0
The	0
percent	0
improvements	0
at	0
six	0
months	0
were	0
as	0
follows	0
:	0
off	0
-	0
period	0
score	0
for	0
overall	0
motor	0
function	0
,	0
28	0
percent	0
(	0
95	0
percent	0
confidence	0
interval	0
,	0
19	0
to	0
38	0
percent	0
)	0
,	0
with	0
most	0
of	0
the	0
improvement	0
in	0
the	0
contralateral	0
limbs	0
;	0
off	0
-	0
period	0
score	0
for	0
activities	0
of	0
daily	0
living	0
,	0
29	0
percent	0
(	0
95	0
percent	0
confidence	0
interval	0
,	0
19	0
to	0
39	0
percent	0
)	0
;	0
on	0
-	0
period	0
score	0
for	0
contralateral	0
dyskinesias	3
,	0
82	0
percent	0
(	0
95	0
percent	0
confidence	0
interval	0
,	0
72	0
to	0
91	0
percent	0
)	0
;	0
and	0
on	0
-	0
period	0
score	0
for	0
ipsilateral	0
dyskinesias	3
,	0
44	0
percent	0
(	0
95	0
percent	0
confidence	0
interval	0
,	0
29	0
to	0
59	0
percent	0
)	0
.	0

The	0
improvements	0
in	0
dyskinesias	3
and	0
the	0
total	0
scores	0
for	0
off	0
-	0
period	0
parkinsonism	3
,	0
contralateral	0
bradykinesia	3
,	0
and	0
rigidity	3
were	0
sustained	0
in	0
the	0
11	0
patients	0
examined	0
at	0
two	0
years	0
.	0

The	0
improvement	0
in	0
ipsilateral	0
dyskinesias	3
was	0
lost	0
after	0
one	0
year	0
,	0
and	0
the	0
improvements	0
in	0
postural	0
stability	0
and	0
gait	0
lasted	0
only	0
three	0
to	0
six	0
months	0
.	0

Approximately	0
half	0
the	0
patients	0
who	0
had	0
been	0
dependent	0
on	0
assistance	0
in	0
activities	0
of	0
daily	0
living	0
in	0
the	0
off	0
period	0
before	0
surgery	0
became	0
independent	0
after	0
surgery	0
.	0

The	0
complications	0
of	0
surgery	0
were	0
generally	0
well	0
tolerated	0
,	0
and	0
there	0
were	0
no	0
significant	0
changes	0
in	0
the	0
use	0
of	0
medication	0
.	0

C0NCLUSI0NS	0
:	0
In	0
late	0
-	0
stage	0
Parkinson	3
'	4
s	4
disease	4
,	0
pallidotomy	0
significantly	0
reduces	0
levodopa	1
-	0
induced	0
dyskinesias	3
and	0
off	0
-	0
period	0
disability	0
.	0

Much	0
of	0
the	0
benefit	0
is	0
sustained	0
at	0
two	0
years	0
,	0
although	0
some	0
improvements	0
,	0
such	0
as	0
those	0
on	0
the	0
ipsilateral	0
side	0
and	0
in	0
axial	0
symptoms	0
,	0
wane	0
within	0
the	0
first	0
year	0
.	0

The	0
on	0
-	0
period	0
symptoms	0
that	0
are	0
resistant	0
to	0
dopaminergic	0
therapy	0
do	0
not	0
respond	0
to	0
pallidotomy	0
.	0

Clarithromycin	1
-	0
induced	0
ventricular	3
tachycardia	4
.	0

Clarithromycin	1
is	0
a	0
relatively	0
new	0
macrolide	1
antibiotic	0
that	0
offers	0
twice	0
-	0
daily	0
dosing	0
.	0

It	0
differs	0
from	0
erythromycin	1
only	0
in	0
the	0
methylation	0
of	0
the	0
hydroxyl	0
group	0
at	0
position	0
6	0
.	0

Although	0
the	0
side	0
-	0
effect	0
profile	0
of	0
erythromycin	1
is	0
established	0
,	0
including	0
gastroenteritis	3
and	0
interactions	0
with	0
other	0
drugs	0
subject	0
to	0
hepatic	0
mixed	0
-	0
function	0
oxidase	0
metabolism	0
,	0
experience	0
with	0
the	0
newer	0
macrolides	1
is	0
still	0
being	0
recorded	0
.	0

Cardiotoxicity	3
has	0
been	0
demonstrated	0
after	0
both	0
intravenous	0
and	0
oral	0
administration	0
of	0
erythromycin	1
but	0
has	0
never	0
been	0
reported	0
with	0
the	0
newer	0
macrolides	1
.	0

We	0
report	0
a	0
case	0
of	0
ventricular	3
dysrhythmias	4
that	0
occurred	0
after	0
six	0
therapeutic	0
doses	0
of	0
clarithromycin	1
.	0

The	0
dysrhythmias	3
resolved	0
after	0
discontinuation	0
of	0
the	0
drug	0
.	0

Effect	0
of	0
glyceryl	1
trinitrate	2
on	0
the	0
sphincter	3
of	4
0ddi	4
spasm	4
evoked	0
by	0
prostigmine	1
-	0
morphine	1
administration	0
.	0

0BJECTIVE	0
:	0
In	0
this	0
study	0
the	0
effect	0
of	0
glyceryl	1
trinitrate	2
on	0
the	0
prostigmine	1
-	0
morphine	1
-	0
induced	0
sphincter	3
of	4
0ddi	4
spasm	4
was	0
evaluated	0
in	0
nine	0
female	0
patients	0
with	0
sphincter	3
of	4
0ddi	4
dyskinesia	4
.	0

METH0D	0
:	0
Sphincter	3
of	4
0ddi	4
spasm	4
was	0
induced	0
by	0
prostigmine	1
-	0
morphine	1
administration	0
(	0
0	0
.	0
5	0
mg	0
prostigmine	1
intramuscularly	0
and	0
10	0
mg	0
morphine	1
subcutaneously	0
)	0
and	0
visualized	0
by	0
quantitative	0
hepatobiliary	0
scintigraphy	0
.	0

The	0
entire	0
procedure	0
was	0
repeated	0
during	0
glyceryl	1
trinitrate	2
infusion	0
(	0
Nitrolingual	1
1	0
microg	0
/	0
kg	0
/	0
min	0
for	0
120	0
min	0
)	0
.	0

RESULTS	0
:	0
Prostigmine	1
-	0
morphine	1
provocation	0
caused	0
significant	0
increases	0
in	0
the	0
time	0
to	0
peak	0
activity	0
(	0
Tmax	0
)	0
over	0
the	0
hepatic	0
hilum	0
(	0
HH	0
:	0
34	0
.	0
33	0
+	0
/	0
-	0
5	0
.	0
05	0
vs	0
.	0
22	0
.	0
77	0
+	0
/	0
-	0
3	0
.	0
26	0
)	0
and	0
the	0
common	0
bile	0
duct	0
(	0
CBD	0
:	0
60	0
.	0
44	0
+	0
/	0
-	0
5	0
.	0
99	0
vs	0
.	0
40	0
.	0
0	0
+	0
/	0
-	0
2	0
.	0
88	0
)	0
and	0
in	0
the	0
half	0
-	0
time	0
of	0
excretion	0
(	0
T1	0
/	0
2	0
)	0
over	0
the	0
liver	0
parenchyma	0
(	0
LP	0
:	0
120	0
.	0
04	0
+	0
/	0
-	0
16	0
.	0
01	0
vs	0
.	0
27	0
.	0
37	0
+	0
/	0
-	0
2	0
.	0
19	0
)	0
,	0
HH	0
(	0
117	0
.	0
61	0
+	0
/	0
-	0
14	0
.	0
71	0
vs	0
.	0
31	0
.	0
85	0
+	0
/	0
-	0
3	0
.	0
99	0
)	0
and	0
CBD	0
(	0
158	0
.	0
11	0
+	0
/	0
-	0
9	0
.	0
18	0
vs	0
.	0
40	0
.	0
1	0
+	0
/	0
-	0
6	0
.	0
24	0
)	0
,	0
indicating	0
a	0
complete	0
spasm	3
at	0
the	0
level	0
of	0
the	0
sphincter	0
of	0
0ddi	0
.	0

Glyceryl	1
trinitrate	2
infusion	0
completely	0
normalized	0
the	0
prostigmine	1
-	0
morphine	1
-	0
induced	0
alterations	0
in	0
these	0
quantitative	0
parameters	0
(	0
TmaX	0
over	0
the	0
LP	0
:	0
11	0
.	0
33	0
+	0
/	0
-	0
1	0
.	0
13	0
;	0
over	0
the	0
HH	0
:	0
18	0
.	0
88	0
+	0
/	0
-	0
1	0
.	0
48	0
;	0
and	0
over	0
the	0
CBD	0
:	0
36	0
.	0
22	0
+	0
/	0
-	0
1	0
.	0
92	0
;	0
and	0
T1	0
/	0
2	0
over	0
the	0
LP	0
:	0
28	0
.	0
21	0
+	0
/	0
-	0
1	0
.	0
83	0
;	0
over	0
the	0
HH	0
:	0
33	0
.	0
42	0
+	0
/	0
-	0
3	0
.	0
10	0
;	0
and	0
over	0
the	0
CBD	0
:	0
41	0
.	0
66	0
+	0
/	0
-	0
6	0
.	0
33	0
)	0
,	0
suggesting	0
an	0
effective	0
sphincter	0
-	0
relaxing	0
effect	0
of	0
glyceryl	1
trinitrate	2
.	0

C0NCLUSI0N	0
:	0
These	0
results	0
provide	0
the	0
first	0
evidence	0
of	0
the	0
effectiveness	0
of	0
glyceryl	1
trinitrate	2
on	0
the	0
morphine	1
-	0
induced	0
sphincter	3
of	4
0ddi	4
spasm	4
in	0
humans	0
.	0

Since	0
glyceryl	1
trinitrate	2
is	0
able	0
to	0
overcome	0
even	0
the	0
drastic	0
effect	0
of	0
morphine	1
,	0
it	0
might	0
be	0
of	0
relevance	0
in	0
the	0
treatment	0
of	0
sphincter	3
of	4
0ddi	4
dyskinesia	4
.	0

Immunopathology	0
of	0
penicillamine	1
-	0
induced	0
glomerular	3
disease	4
.	0

Four	0
patients	0
with	0
rheumatoid	3
arthritis	4
developed	0
heavy	0
proteinuria	3
after	0
five	0
to	0
12	0
months	0
of	0
treatment	0
with	0
D	1
-	2
penicillamine	2
.	0

Light	0
microscopy	0
of	0
renal	0
biopsy	0
samples	0
showed	0
minimal	0
glomerular	0
capillary	0
wall	0
thickening	0
and	0
mesangial	0
matrix	0
increase	0
,	0
or	0
no	0
departure	0
from	0
normal	0
.	0

Electron	0
microscopy	0
,	0
however	0
,	0
revealed	0
subepithelial	0
electron	0
-	0
dense	0
deposits	0
,	0
fusion	0
of	0
epithelial	0
cell	0
foot	0
processes	0
,	0
and	0
evidence	0
of	0
mesangial	0
cell	0
hyperactivity	0
.	0

Immunofluorescence	0
microscopy	0
demonstrated	0
granular	0
capillary	0
wall	0
deposits	0
of	0
IgG	0
and	0
C3	0
.	0

The	0
findings	0
were	0
similar	0
to	0
those	0
in	0
early	0
membranous	3
glomerulonephritis	4
,	0
differences	0
being	0
observed	0
however	0
in	0
the	0
results	0
of	0
staining	0
for	0
the	0
early	0
-	0
acting	0
complement	0
components	0
C1q	0
and	0
C4	0
.	0

It	0
is	0
tentatively	0
concluded	0
that	0
complement	0
was	0
activated	0
by	0
the	0
classical	0
pathway	0
.	0

Experimental	0
cranial	0
pain	3
elicited	0
by	0
capsaicin	1
:	0
a	0
PET	0
study	0
.	0

Using	0
a	0
positron	0
emission	0
tomography	0
(	0
PET	0
)	0
study	0
it	0
was	0
shown	0
recently	0
that	0
in	0
migraine	3
without	0
aura	0
certain	0
areas	0
in	0
the	0
brain	0
stem	0
were	0
activated	0
during	0
the	0
headache	3
state	0
,	0
but	0
not	0
in	0
the	0
headache	3
free	0
interval	0
.	0

It	0
was	0
suggested	0
that	0
this	0
brain	0
stem	0
activation	0
is	0
inherent	0
to	0
the	0
migraine	3
attack	0
itself	0
and	0
represents	0
the	0
so	0
called	0
'	0
migraine	3
generator	0
'	0
.	0

To	0
test	0
this	0
hypothesis	0
we	0
performed	0
an	0
experimental	0
pain	3
study	0
in	0
seven	0
healthy	0
volunteers	0
,	0
using	0
the	0
same	0
positioning	0
in	0
the	0
PET	0
scanner	0
as	0
in	0
the	0
migraine	3
patients	0
.	0

A	0
small	0
amount	0
of	0
capsaicin	1
was	0
administered	0
subcutaneously	0
in	0
the	0
right	0
forehead	0
to	0
evoke	0
a	0
burning	0
painful	3
sensation	0
in	0
the	0
first	0
division	0
of	0
the	0
trigeminal	0
nerve	0
.	0

Increases	0
of	0
regional	0
cerebral	0
blood	0
flow	0
(	0
rCBF	0
)	0
were	0
found	0
bilaterally	0
in	0
the	0
insula	0
,	0
in	0
the	0
anterior	0
cingulate	0
cortex	0
,	0
the	0
cavernous	0
sinus	0
and	0
the	0
cerebellum	0
.	0

Using	0
the	0
same	0
stereotactic	0
space	0
limits	0
as	0
in	0
the	0
above	0
mentioned	0
migraine	3
study	0
no	0
brain	0
stem	0
activation	0
was	0
found	0
in	0
the	0
acute	0
pain	3
state	0
compared	0
to	0
the	0
pain	3
free	0
state	0
.	0

The	0
increase	0
of	0
activation	0
in	0
the	0
region	0
of	0
the	0
cavernous	0
sinus	0
however	0
,	0
suggests	0
that	0
this	0
structure	0
is	0
more	0
likely	0
to	0
be	0
involved	0
in	0
trigeminal	0
transmitted	0
pain	3
as	0
such	0
,	0
rather	0
than	0
in	0
a	0
specific	0
type	0
of	0
headache	3
as	0
was	0
suggested	0
for	0
cluster	3
headache	4
.	0

Value	0
of	0
methylprednisolone	1
in	0
prevention	0
of	0
the	0
arthralgia	3
-	0
myalgia	3
syndrome	0
associated	0
with	0
the	0
total	0
dose	0
infusion	0
of	0
iron	1
dextran	2
:	0
a	0
double	0
blind	0
randomized	0
trial	0
.	0

The	0
safety	0
and	0
efficacy	0
of	0
total	0
dose	0
infusion	0
(	0
TDI	0
)	0
of	0
iron	1
dextran	2
has	0
been	0
well	0
documented	0
.	0

In	0
40	0
%	0
of	0
treated	0
patients	0
,	0
an	0
arthralgia	3
-	0
myalgia	3
syndrome	0
develops	0
.	0

The	0
purpose	0
of	0
this	0
randomized	0
,	0
double	0
-	0
blind	0
,	0
prospective	0
study	0
was	0
to	0
investigate	0
whether	0
intravenous	0
(	0
i	0
.	0
v	0
.	0
)	0
administration	0
of	0
methylprednisolone	1
(	0
MP	1
)	0
prevents	0
this	0
complication	0
.	0

Sixty	0
-	0
five	0
patients	0
,	0
34	0
women	0
and	0
31	0
men	0
,	0
ages	0
36	0
to	0
80	0
years	0
,	0
received	0
either	0
normal	0
saline	0
before	0
and	0
after	0
TDI	0
(	0
group	0
1	0
)	0
,	0
125	0
mg	0
i	0
.	0
v	0
.	0
MP	1
before	0
and	0
saline	0
after	0
TDI	0
(	0
group	0
2	0
)	0
,	0
or	0
125	0
mg	0
i	0
.	0
v	0
.	0
MP	1
before	0
and	0
after	0
TDI	0
(	0
group	0
3	0
)	0
.	0

Patients	0
were	0
observed	0
for	0
72	0
hours	0
and	0
reactions	0
were	0
recorded	0
and	0
graded	0
according	0
to	0
severity	0
.	0

Fifty	0
-	0
eight	0
percent	0
of	0
group	0
1	0
patients	0
,	0
33	0
%	0
of	0
group	0
2	0
,	0
and	0
26	0
%	0
of	0
group	0
3	0
had	0
reactions	0
to	0
TDI	0
.	0

The	0
severity	0
of	0
reactions	0
(	0
minimal	0
,	0
mild	0
,	0
and	0
moderate	0
,	0
respectively	0
)	0
was	0
as	0
follows	0
:	0
group	0
1	0
-	0
-	0
6	0
,	0
6	0
,	0
and	0
2	0
;	0
group	0
2	0
-	0
-	0
1	0
,	0
5	0
,	0
and	0
0	0
;	0
group	0
3	0
-	0
-	0
5	0
,	0
1	0
,	0
and	0
0	0
.	0

Data	0
were	0
analyzed	0
by	0
the	0
two	0
-	0
sided	0
Fisher	0
'	0
s	0
exact	0
test	0
using	0
95	0
%	0
confidence	0
intervals	0
with	0
the	0
approximation	0
of	0
Woolf	0
.	0

These	0
data	0
demonstrate	0
that	0
administration	0
of	0
MP	1
before	0
and	0
after	0
TDI	0
reduces	0
the	0
frequency	0
and	0
severity	0
of	0
the	0
arthralgia	3
-	0
myalgia	3
syndrome	0
.	0

We	0
conclude	0
that	0
125	0
mg	0
i	0
.	0
v	0
.	0
MP	1
should	0
be	0
given	0
routinely	0
before	0
and	0
after	0
TDI	0
of	0
iron	1
dextran	2
.	0

Prolongation	3
of	4
the	4
QT	4
interval	4
related	0
to	0
cisapride	1
-	0
diltiazem	1
interaction	0
.	0

Cisapride	1
,	0
a	0
cytochrome	0
P450	0
3A4	0
(	0
CYP3A4	0
)	0
substrate	0
,	0
is	0
widely	0
prescribed	0
for	0
the	0
treatment	0
of	0
gastrointestinal	3
motility	4
disorders	4
.	0

Prolongation	3
of	4
QT	4
interval	4
,	0
torsades	3
de	4
pointes	4
,	0
and	0
sudden	3
cardiac	4
death	4
have	0
been	0
reported	0
after	0
concomitant	0
administration	0
with	0
erythromycin	1
or	0
azole	1
antifungal	0
agents	0
,	0
but	0
not	0
with	0
other	0
CYP3A4	0
inhibitors	0
.	0

A	0
possible	0
drug	0
interaction	0
occurred	0
in	0
a	0
45	0
-	0
year	0
-	0
old	0
woman	0
who	0
was	0
taking	0
cisapride	1
for	0
gastroesophageal	3
reflux	4
disorder	4
and	0
diltiazem	1
,	0
an	0
agent	0
that	0
has	0
inhibitory	0
effect	0
on	0
CYP3A4	0
,	0
for	0
hypertension	3
.	0

The	0
patient	0
was	0
in	0
near	0
syncope	3
and	0
had	0
QT	3
-	4
interval	4
prolongation	4
.	0

After	0
discontinuing	0
cisapride	1
,	0
the	0
QT	0
interval	0
returned	0
to	0
normal	0
and	0
symptoms	0
did	0
not	0
recur	0
.	0

We	0
suggest	0
that	0
caution	0
be	0
taken	0
when	0
cisapride	1
is	0
prescribed	0
with	0
any	0
potent	0
inhibitor	0
of	0
CYP3A4	0
,	0
including	0
diltiazem	1
.	0

Cortical	0
motor	0
overactivation	0
in	0
parkinsonian	3
patients	0
with	0
L	1
-	2
dopa	2
-	0
induced	0
peak	0
-	0
dose	0
dyskinesia	3
.	0

We	0
have	0
studied	0
the	0
regional	0
cerebral	0
blood	0
flow	0
(	0
rCBF	0
)	0
changes	0
induced	0
by	0
the	0
execution	0
of	0
a	0
finger	0
-	0
to	0
-	0
thumb	0
opposition	0
motor	0
task	0
in	0
the	0
supplementary	0
and	0
primary	0
motor	0
cortex	0
of	0
two	0
groups	0
of	0
parkinsonian	3
patients	0
on	0
L	1
-	2
dopa	2
medication	0
,	0
the	0
first	0
one	0
without	0
L	1
-	2
dopa	2
induced	0
dyskinesia	3
(	0
n	0
=	0
23	0
)	0
and	0
the	0
other	0
with	0
moderate	0
peak	0
-	0
dose	0
dyskinesia	3
(	0
n	0
=	0
15	0
)	0
,	0
and	0
of	0
a	0
group	0
of	0
14	0
normal	0
subjects	0
.	0

Single	0
photon	0
emission	0
tomography	0
with	0
i	0
.	0
v	0
.	0
133Xe	0
was	0
used	0
to	0
measure	0
the	0
rCBF	0
changes	0
.	0

The	0
dyskinetic	3
parkinsonian	3
patients	0
exhibited	0
a	0
pattern	0
of	0
response	0
which	0
was	0
markedly	0
different	0
from	0
those	0
of	0
the	0
normal	0
subjects	0
and	0
non	0
-	0
dyskinetic	3
parkinsonian	3
patients	0
,	0
with	0
a	0
significant	0
overactivation	0
in	0
the	0
supplementary	0
motor	0
area	0
and	0
the	0
ipsi	0
-	0
and	0
contralateral	0
primary	0
motor	0
areas	0
.	0

These	0
results	0
are	0
compatible	0
with	0
the	0
hypothesis	0
that	0
an	0
hyperkinetic	3
abnormal	3
involuntary	4
movement	4
,	0
like	0
L	1
-	2
dopa	2
-	0
induced	0
peak	0
dose	0
dyskinesia	3
,	0
is	0
due	0
to	0
a	0
disinhibition	0
of	0
the	0
primary	0
and	0
associated	0
motor	0
cortex	0
secondary	0
to	0
an	0
excessive	0
outflow	0
of	0
the	0
pallidothalamocortical	0
motor	0
loop	0
.	0

0pen	0
-	0
label	0
assessment	0
of	0
levofloxacin	1
for	0
the	0
treatment	0
of	0
acute	0
bacterial	0
sinusitis	3
in	0
adults	0
.	0

PURP0SE	0
:	0
To	0
evaluate	0
the	0
efficacy	0
and	0
safety	0
of	0
levofloxacin	1
(	0
500	0
mg	0
orally	0
once	0
daily	0
for	0
10	0
to	0
14	0
days	0
)	0
in	0
treating	0
adult	0
outpatients	0
with	0
acute	0
bacterial	0
sinusitis	3
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
A	0
total	0
of	0
329	0
patients	0
enrolled	0
in	0
the	0
study	0
at	0
24	0
centers	0
.	0

All	0
patients	0
had	0
a	0
pre	0
-	0
therapy	0
Gram	0
'	0
s	0
stain	0
and	0
culture	0
of	0
sinus	0
exudate	0
obtained	0
by	0
antral	0
puncture	0
or	0
nasal	0
endoscopy	0
.	0

Clinical	0
response	0
was	0
assessed	0
on	0
the	0
basis	0
of	0
signs	0
and	0
symptoms	0
and	0
sinus	0
radiograph	0
or	0
computed	0
tomography	0
results	0
.	0

Microbiologic	0
cure	0
rates	0
were	0
determined	0
on	0
the	0
basis	0
of	0
presumed	0
plus	0
documented	0
eradication	0
of	0
the	0
pre	0
-	0
therapy	0
pathogen	0
(	0
s	0
)	0
.	0

RESULTS	0
:	0
The	0
most	0
common	0
pathogens	0
were	0
Haemophilus	0
influenzae	0
,	0
Streptococcus	0
pneumoniae	0
,	0
Staphylococcus	0
aureus	0
,	0
and	0
Moraxella	0
catarrhalis	0
.	0

0f	0
300	0
clinically	0
evaluable	0
patients	0
,	0
175	0
(	0
58	0
%	0
)	0
were	0
cured	0
and	0
90	0
(	0
30	0
%	0
)	0
were	0
improved	0
at	0
the	0
post	0
-	0
therapy	0
evaluation	0
,	0
resulting	0
in	0
a	0
clinical	0
success	0
rate	0
of	0
88	0
%	0
.	0

Thirty	0
-	0
five	0
patients	0
(	0
12	0
%	0
)	0
clinically	0
failed	0
treatment	0
.	0

The	0
microbiologic	0
eradication	0
rate	0
(	0
presumed	0
plus	0
documented	0
)	0
among	0
138	0
microbiologically	0
evaluable	0
patients	0
was	0
92	0
%	0
.	0

Microbiologic	0
eradication	0
rates	0
(	0
presumed	0
plus	0
documented	0
)	0
of	0
the	0
most	0
common	0
pathogens	0
ranged	0
from	0
93	0
%	0
(	0
M	0
.	0
catarrhalis	0
)	0
to	0
100	0
%	0
(	0
S	0
.	0
pneumoniae	0
)	0
at	0
the	0
post	0
-	0
therapy	0
visit	0
.	0

All	0
but	0
one	0
of	0
the	0
265	0
patients	0
who	0
were	0
cured	0
or	0
improved	0
at	0
post	0
-	0
therapy	0
returned	0
for	0
a	0
long	0
-	0
term	0
follow	0
-	0
up	0
visit	0
;	0
243	0
(	0
92	0
%	0
)	0
remained	0
well	0
4	0
to	0
6	0
weeks	0
after	0
therapy	0
;	0
and	0
21	0
(	0
8	0
%	0
)	0
had	0
a	0
relapse	0
of	0
symptoms	0
.	0

Adverse	0
events	0
considered	0
to	0
be	0
related	0
to	0
levofloxacin	1
administration	0
were	0
reported	0
by	0
29	0
patients	0
(	0
9	0
%	0
)	0
.	0

The	0
most	0
common	0
drug	0
-	0
related	0
adverse	0
events	0
were	0
diarrhea	3
,	0
flatulence	3
,	0
and	0
nausea	3
;	0
most	0
adverse	0
events	0
were	0
mild	0
to	0
moderate	0
in	0
severity	0
.	0

C0NCLUSI0N	0
:	0
The	0
results	0
of	0
this	0
study	0
indicate	0
that	0
levofloxacin	1
500	0
mg	0
once	0
daily	0
is	0
an	0
effective	0
and	0
safe	0
treatment	0
for	0
acute	0
bacterial	0
sinusitis	3
.	0

Iatrogenic	0
risks	0
of	0
endometrial	3
carcinoma	4
after	0
treatment	0
for	0
breast	3
cancer	4
in	0
a	0
large	0
French	0
case	0
-	0
control	0
study	0
.	0

F	0
d	0
ration	0
Nationale	0
des	0
Centres	0
de	0
Lutte	0
Contre	0
le	0
Cancer	0
(	0
FNCLCC	0
)	0
.	0

Since	0
tamoxifen	1
is	0
widely	0
used	0
in	0
breast	3
cancer	4
treatment	0
and	0
has	0
been	0
proposed	0
for	0
the	0
prevention	0
of	0
breast	3
cancer	4
,	0
its	0
endometrial	0
iatrogenic	0
effects	0
must	0
be	0
carefully	0
examined	0
.	0

We	0
have	0
investigated	0
the	0
association	0
between	0
endometrial	3
cancer	4
and	0
tamoxifen	1
use	0
or	0
other	0
treatments	0
in	0
women	0
treated	0
for	0
breast	3
cancer	4
in	0
a	0
case	0
-	0
control	0
study	0
.	0

Cases	0
of	0
endometrial	3
cancer	4
diagnosed	0
after	0
breast	3
cancer	4
(	0
n	0
=	0
135	0
)	0
and	0
467	0
controls	0
matched	0
for	0
age	0
,	0
year	0
of	0
diagnosis	0
of	0
breast	3
cancer	4
and	0
hospital	0
and	0
survival	0
time	0
with	0
an	0
intact	0
uterus	0
were	0
included	0
.	0

Women	0
who	0
had	0
received	0
tamoxifen	1
were	0
significantly	0
more	0
likely	0
to	0
have	0
endometrial	3
cancer	4
diagnosed	0
than	0
those	0
who	0
had	0
not	0
(	0
crude	0
relative	0
risk	0
=	0
4	0
.	0
9	0
,	0
p	0
=	0
0	0
.	0
0001	0
)	0
.	0

Univariate	0
and	0
adjusted	0
analyses	0
showed	0
that	0
the	0
risk	0
increased	0
with	0
the	0
length	0
of	0
treatment	0
(	0
p	0
=	0
0	0
.	0
0001	0
)	0
or	0
the	0
cumulative	0
dose	0
of	0
tamoxifen	1
received	0
(	0
p	0
=	0
0	0
.	0
0001	0
)	0
,	0
irrespective	0
of	0
the	0
daily	0
dose	0
.	0

Women	0
who	0
had	0
undergone	0
pelvic	0
radiotherapy	0
also	0
had	0
a	0
higher	0
risk	0
(	0
crude	0
relative	0
risk	0
=	0
7	0
.	0
8	0
,	0
p	0
=	0
0	0
.	0
0001	0
)	0
.	0

After	0
adjusting	0
for	0
confounding	0
factors	0
,	0
the	0
risk	0
was	0
higher	0
for	0
tamoxifen	1
users	0
(	0
p	0
=	0
0	0
.	0
0012	0
)	0
,	0
treatment	0
for	0
more	0
than	0
3	0
years	0
(	0
all	0
p	0
<	0
0	0
.	0
03	0
)	0
and	0
pelvic	0
radiotherapy	0
(	0
p	0
=	0
0	0
.	0
012	0
)	0
.	0

Women	0
who	0
had	0
endometrial	3
cancer	4
and	0
had	0
received	0
tamoxifen	1
had	0
more	0
advanced	3
disease	4
and	0
poorer	0
prognosis	0
than	0
those	0
with	0
endometrial	3
cancer	4
who	0
had	0
not	0
received	0
this	0
treatment	0
.	0

0ur	0
results	0
suggest	0
a	0
causal	0
role	0
of	0
tamoxifen	1
in	0
endometrial	3
cancer	4
,	0
particularly	0
when	0
used	0
as	0
currently	0
proposed	0
for	0
breast	3
cancer	4
prevention	0
.	0

Pelvic	0
radiotherapy	0
may	0
be	0
an	0
additional	0
iatrogenic	0
factor	0
for	0
women	0
with	0
breast	3
cancer	4
.	0

Endometrial	3
cancers	4
diagnosed	0
in	0
women	0
treated	0
with	0
tamoxifen	1
have	0
poorer	0
prognosis	0
.	0

Women	0
who	0
receive	0
tamoxifen	1
for	0
breast	3
cancer	4
should	0
be	0
offered	0
gynaecological	0
surveillance	0
during	0
and	0
after	0
treatment	0
.	0

A	0
long	0
-	0
term	0
evaluation	0
of	0
the	0
risk	0
-	0
benefit	0
ratio	0
of	0
tamoxifen	1
as	0
a	0
preventive	0
treatment	0
for	0
breast	3
cancer	4
is	0
clearly	0
warranted	0
.	0

Contribution	0
of	0
the	0
glycine	1
site	0
of	0
NMDA	1
receptors	0
in	0
rostral	0
and	0
intermediate	0
-	0
caudal	0
parts	0
of	0
the	0
striatum	0
to	0
the	0
regulation	0
of	0
muscle	0
tone	0
in	0
rats	0
.	0

The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
assess	0
the	0
contribution	0
of	0
the	0
glycine	1
site	0
of	0
NMDA	1
receptors	0
in	0
the	0
striatum	0
to	0
the	0
regulation	0
of	0
muscle	0
tone	0
.	0

Muscle	0
tone	0
was	0
examined	0
using	0
a	0
combined	0
mechanoand	0
electromyographic	0
method	0
,	0
which	0
measured	0
simultaneously	0
the	0
muscle	0
resistance	0
(	0
MMG	0
)	0
of	0
the	0
rat	0
'	0
s	0
hind	0
foot	0
to	0
passive	0
extension	0
and	0
flexion	0
in	0
the	0
ankle	0
joint	0
and	0
the	0
electromyographic	0
activity	0
(	0
EMG	0
)	0
of	0
the	0
antagonistic	0
muscles	0
of	0
that	0
joint	0
:	0
gastrocnemius	0
and	0
tibialis	0
anterior	0
.	0

Muscle	3
rigidity	4
was	0
induced	0
by	0
haloperidol	1
(	0
2	0
.	0
5	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
.	0

5	1
,	2
7	2
-	2
dichlorokynurenic	2
acid	2
(	0
5	1
,	2
7	2
-	2
DCKA	2
)	0
,	0
a	0
selective	0
glycine	1
site	0
antagonist	0
,	0
injected	0
in	0
doses	0
of	0
2	0
.	0
5	0
and	0
4	0
.	0
5	0
microg	0
/	0
0	0
.	0
5	0
microl	0
bilaterally	0
,	0
into	0
the	0
rostral	0
region	0
of	0
the	0
striatum	0
,	0
decreased	0
both	0
the	0
haloperidol	1
-	0
induced	0
muscle	3
rigidity	4
(	0
MMG	0
)	0
and	0
the	0
enhanced	0
electromyographic	0
activity	0
(	0
EMG	0
)	0
.	0

5	1
,	2
7	2
-	2
DCKA	2
injected	0
bilaterally	0
in	0
a	0
dose	0
of	0
4	0
.	0
5	0
microg	0
/	0
0	0
.	0
5	0
microl	0
into	0
the	0
intermediate	0
-	0
caudal	0
region	0
of	0
the	0
striatum	0
of	0
rats	0
not	0
pretreated	0
with	0
haloperidol	1
had	0
no	0
effect	0
on	0
the	0
muscle	0
tone	0
.	0

The	0
present	0
results	0
suggest	0
that	0
blockade	0
of	0
the	0
glycine	1
site	0
of	0
NMDA	1
receptors	0
in	0
the	0
rostral	0
part	0
of	0
the	0
striatum	0
may	0
be	0
mainly	0
responsible	0
for	0
the	0
antiparkinsonian	0
action	0
of	0
this	0
drug	0
.	0

Carboplatin	1
toxic	0
effects	0
on	0
the	0
peripheral	0
nervous	0
system	0
of	0
the	0
rat	0
.	0

BACKGR0UND	0
:	0
The	0
most	0
striking	0
of	0
carboplatin	1
'	0
s	0
advantages	0
(	0
CBDCA	1
)	0
over	0
cisplatin	1
(	0
CDDP	1
)	0
is	0
its	0
markedly	0
reduced	0
rate	0
of	0
neurotoxic	3
effects	0
.	0

However	0
,	0
the	0
use	0
of	0
CBDCA	1
higher	0
-	0
intensity	0
schedules	0
and	0
the	0
association	0
with	0
other	0
neurotoxic	3
drugs	0
in	0
polychemotherapy	0
may	0
cause	0
some	0
concern	0
about	0
its	0
safety	0
with	0
respect	0
to	0
peripheral	3
nervous	4
system	4
damage	4
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
Two	0
different	0
schedules	0
of	0
CBDCA	1
administration	0
(	0
10	0
mg	0
/	0
kg	0
and	0
15	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
twice	0
a	0
week	0
for	0
nine	0
times	0
)	0
were	0
evaluated	0
in	0
Wistar	0
rats	0
.	0

Neurotoxicity	3
was	0
assessed	0
for	0
behavioral	0
(	0
tail	0
-	0
flick	0
test	0
)	0
,	0
neurophysiological	0
(	0
nerve	0
conduction	0
velocity	0
in	0
the	0
tail	0
nerve	0
)	0
,	0
morphological	0
,	0
morphometrical	0
and	0
analytical	0
effects	0
.	0

RESULTS	0
:	0
CBDCA	1
administration	0
induced	0
dose	0
-	0
dependent	0
peripheral	3
neurotoxicity	4
.	0

Pain	3
perception	0
and	0
nerve	0
conduction	0
velocity	0
in	0
the	0
tail	0
were	0
significantly	0
impaired	0
,	0
particularly	0
after	0
the	0
high	0
-	0
dose	0
treatment	0
.	0

The	0
dorsal	0
root	0
ganglia	0
sensory	0
neurons	0
and	0
,	0
to	0
a	0
lesser	0
extent	0
,	0
satellite	0
cells	0
showed	0
the	0
same	0
changes	0
as	0
those	0
induced	0
by	0
CDDP	1
,	0
mainly	0
affecting	0
the	0
nucleus	0
and	0
nucleolus	0
of	0
ganglionic	0
sensory	0
neurons	0
.	0

Moreover	0
,	0
significant	0
amounts	0
of	0
platinum	1
were	0
detected	0
in	0
the	0
dorsal	0
root	0
ganglia	0
and	0
kidney	0
after	0
CBDCA	1
treatment	0
.	0

C0NCLUSI0NS	0
:	0
CBDCA	1
is	0
neurotoxic	3
in	0
our	0
model	0
,	0
and	0
the	0
type	0
of	0
pathological	0
changes	0
it	0
induces	0
are	0
so	0
closely	0
similar	0
to	0
those	0
caused	0
by	0
CDDP	1
that	0
it	0
is	0
probable	0
that	0
neurotoxicity	3
is	0
induced	0
in	0
the	0
two	0
drugs	0
by	0
the	0
same	0
mechanism	0
.	0

This	0
model	0
can	0
be	0
used	0
alone	0
or	0
in	0
combination	0
with	0
other	0
drugs	0
to	0
explore	0
the	0
effect	0
of	0
CBDCA	1
on	0
the	0
peripheral	0
nervous	0
system	0
.	0

Effects	0
of	0
cisapride	1
on	0
symptoms	0
and	0
postcibal	0
small	0
-	0
bowel	0
motor	0
function	0
in	0
patients	0
with	0
irritable	3
bowel	4
syndrome	4
.	0

BACKGR0UND	0
:	0
Irritable	3
bowel	4
syndrome	4
is	0
a	0
common	0
cause	0
of	0
abdominal	3
pain	4
and	0
discomfort	0
and	0
may	0
be	0
related	0
to	0
disordered	3
gastrointestinal	4
motility	4
.	0

0ur	0
aim	0
was	0
to	0
assess	0
the	0
effects	0
of	0
long	0
-	0
term	0
treatment	0
with	0
a	0
prokinetic	0
agent	0
,	0
cisapride	1
,	0
on	0
postprandial	0
jejunal	0
motility	0
and	0
symptoms	0
in	0
the	0
irritable	3
bowel	4
syndrome	4
(	0
IBS	3
)	0
.	0

METH0DS	0
:	0
Thirty	0
-	0
eight	0
patients	0
with	0
IBS	3
(	0
constipation	3
-	0
predominant	0
,	0
n	0
=	0
17	0
;	0
diarrhoea	3
-	0
predominant	0
,	0
n	0
=	0
21	0
)	0
underwent	0
24	0
-	0
h	0
ambulatory	0
jejunal	0
manometry	0
before	0
and	0
after	0
12	0
week	0
'	0
s	0
treatment	0
[	0
cisapride	1
,	0
5	0
mg	0
three	0
times	0
daily	0
(	0
n	0
=	0
19	0
)	0
or	0
placebo	0
(	0
n	0
=	0
19	0
)	0
]	0
.	0

RESULTS	0
:	0
In	0
diarrhoea	3
-	0
predominant	0
patients	0
significant	0
differences	0
in	0
contraction	0
characteristics	0
were	0
observed	0
between	0
the	0
cisapride	1
and	0
placebo	0
groups	0
.	0

In	0
cisapride	1
-	0
treated	0
diarrhoea	3
-	0
predominant	0
patients	0
the	0
mean	0
contraction	0
amplitude	0
was	0
higher	0
(	0
29	0
.	0
3	0
+	0
/	0
-	0
3	0
.	0
2	0
versus	0
24	0
.	0
9	0
+	0
/	0
-	0
2	0
.	0
6	0
mm	0
Hg	0
,	0
cisapride	1
versus	0
placebo	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
;	0
pretreatment	0
,	0
25	0
.	0
7	0
+	0
/	0
-	0
6	0
.	0
0	0
mm	0
Hg	0
)	0
,	0
the	0
mean	0
contraction	0
duration	0
longer	0
(	0
3	0
.	0
4	0
+	0
/	0
-	0
0	0
.	0
2	0
versus	0
3	0
.	0
0	0
+	0
/	0
-	0
0	0
.	0
2	0
sec	0
,	0
cisapride	1
versus	0
placebo	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
;	0
pretreatment	0
,	0
3	0
.	0
1	0
+	0
/	0
-	0
0	0
.	0
5	0
sec	0
)	0
,	0
and	0
the	0
mean	0
contraction	0
frequency	0
lower	0
(	0
2	0
.	0
0	0
+	0
/	0
-	0
0	0
.	0
2	0
versus	0
2	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
4	0
cont	0
.	0
/	0
min	0
,	0
cisapride	1
versus	0
placebo	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
;	0
pretreatment	0
,	0
2	0
.	0
5	0
+	0
/	0
-	0
1	0
.	0
1	0
cont	0
.	0
/	0
min	0
]	0
than	0
patients	0
treated	0
with	0
placebo	0
.	0

No	0
significant	0
differences	0
in	0
jejunal	0
motility	0
were	0
found	0
in	0
the	0
constipation	3
-	0
predominant	0
IBS	3
group	0
.	0

Symptoms	0
were	0
assessed	0
by	0
using	0
a	0
visual	0
analogue	0
scale	0
before	0
and	0
after	0
treatment	0
.	0

Symptom	0
scores	0
relating	0
to	0
the	0
severity	0
of	0
constipation	3
were	0
lower	0
in	0
cisapride	1
-	0
treated	0
constipation	3
-	0
predominant	0
IBS	3
patients	0
[	0
score	0
,	0
54	0
+	0
/	0
-	0
5	0
versus	0
67	0
+	0
/	0
-	0
14	0
mm	0
,	0
cisapride	1
versus	0
placebo	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
;	0
pretreatment	0
,	0
62	0
+	0
/	0
-	0
19	0
mm	0
]	0
.	0

Diarrhoea	3
-	0
predominant	0
IBS	3
patients	0
had	0
a	0
higher	0
pain	3
score	0
after	0
cisapride	1
therapy	0
[	0
score	0
,	0
55	0
+	0
/	0
-	0
15	0
versus	0
34	0
+	0
/	0
-	0
12	0
mm	0
,	0
cisapride	1
versus	0
placebo	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
;	0
pretreatment	0
,	0
67	0
+	0
/	0
-	0
19	0
mm	0
]	0
.	0

C0NCLUSI0N	0
:	0
Cisapride	1
affects	0
jejunal	0
contraction	0
characteristics	0
and	0
some	0
symptoms	0
in	0
IBS	3
.	0

Prevention	0
of	0
breast	3
cancer	4
with	0
tamoxifen	1
:	0
preliminary	0
findings	0
from	0
the	0
Italian	0
randomised	0
trial	0
among	0
hysterectomised	0
women	0
.	0

Italian	0
Tamoxifen	1
Prevention	0
Study	0
.	0

BACKGR0UND	0
:	0
Tamoxifen	1
is	0
a	0
candidate	0
chemopreventive	0
agent	0
in	0
breast	3
cancer	4
,	0
although	0
the	0
drug	0
may	0
be	0
associated	0
with	0
the	0
development	0
of	0
endometrial	3
cancer	4
.	0

Therefore	0
we	0
did	0
a	0
trial	0
in	0
hysterectomised	0
women	0
of	0
tamoxifen	1
as	0
a	0
chemopreventive	0
.	0

METH0DS	0
:	0
In	0
0ctober	0
,	0
1992	0
,	0
we	0
started	0
a	0
double	0
-	0
blind	0
placebo	0
-	0
controlled	0
,	0
randomised	0
trial	0
of	0
tamoxifen	1
in	0
women	0
(	0
mainly	0
in	0
Italy	0
)	0
who	0
did	0
not	0
have	0
breast	3
cancer	4
and	0
who	0
had	0
had	0
a	0
hysterectomy	0
.	0

Women	0
were	0
randomised	0
to	0
receive	0
tamoxifen	1
20	0
mg	0
per	0
day	0
or	0
placebo	0
,	0
both	0
orally	0
for	0
5	0
years	0
.	0

The	0
original	0
plan	0
was	0
to	0
follow	0
the	0
intervention	0
phase	0
by	0
5	0
years	0
'	0
follow	0
-	0
up	0
.	0

In	0
June	0
,	0
1997	0
,	0
the	0
trialists	0
and	0
the	0
data	0
-	0
monitoring	0
committee	0
decided	0
to	0
end	0
recruitment	0
primarily	0
because	0
of	0
the	0
number	0
of	0
women	0
dropping	0
out	0
of	0
the	0
study	0
.	0

Recruitment	0
ended	0
on	0
July	0
11	0
,	0
1997	0
,	0
and	0
the	0
study	0
will	0
continue	0
as	0
planned	0
.	0

The	0
primary	0
endpoints	0
are	0
the	0
occurrence	0
of	0
and	0
deaths	0
from	0
breast	3
cancer	4
.	0

This	0
preliminary	0
interim	0
analysis	0
is	0
based	0
on	0
intention	0
-	0
to	0
-	0
treat	0
.	0

FINDINGS	0
:	0
5408	0
women	0
were	0
randomised	0
;	0
participating	0
women	0
have	0
a	0
median	0
follow	0
-	0
up	0
of	0
46	0
months	0
for	0
major	0
endpoints	0
.	0

41	0
cases	0
of	0
breast	3
cancer	4
occurred	0
so	0
far	0
;	0
there	0
have	0
been	0
no	0
deaths	0
from	0
breast	3
cancer	4
.	0

There	0
is	0
no	0
difference	0
in	0
breast	3
-	4
cancer	4
frequency	0
between	0
the	0
placebo	0
(	0
22	0
cases	0
)	0
and	0
tamoxifen	1
(	0
19	0
)	0
arms	0
.	0

There	0
is	0
a	0
statistically	0
significant	0
reduction	0
of	0
breast	3
cancer	4
among	0
women	0
receiving	0
tamoxifen	1
who	0
also	0
used	0
hormone	0
-	0
replacement	0
therapy	0
during	0
the	0
trial	0
:	0
among	0
390	0
women	0
on	0
such	0
therapy	0
and	0
allocated	0
to	0
placebo	0
,	0
we	0
found	0
eight	0
cases	0
of	0
breast	3
cancer	4
compared	0
with	0
one	0
case	0
among	0
362	0
women	0
allocated	0
to	0
tamoxifen	1
.	0

Compared	0
with	0
the	0
placebo	0
group	0
,	0
there	0
was	0
a	0
significantly	0
increased	0
risk	0
of	0
vascular	3
events	4
and	0
hypertriglyceridaemia	3
among	0
women	0
on	0
tamoxifen	1
.	0

INTERPRETATI0N	0
:	0
Although	0
this	0
preliminary	0
analysis	0
has	0
low	0
power	0
,	0
in	0
this	0
cohort	0
of	0
women	0
at	0
low	0
-	0
to	0
-	0
normal	0
risk	0
of	0
breast	3
cancer	4
,	0
the	0
postulated	0
protective	0
effects	0
of	0
tamoxifen	1
are	0
not	0
yet	0
apparent	0
.	0

Women	0
using	0
hormone	0
-	0
replacement	0
therapy	0
appear	0
to	0
have	0
benefited	0
from	0
use	0
of	0
tamoxifen	1
.	0

There	0
were	0
no	0
deaths	0
from	0
breast	3
cancer	4
recorded	0
in	0
women	0
in	0
the	0
study	0
.	0

It	0
is	0
essential	0
to	0
continue	0
follow	0
-	0
up	0
to	0
quantify	0
the	0
long	0
-	0
term	0
risks	0
and	0
benefits	0
of	0
tamoxifen	1
therapy	0
.	0

Epileptogenic	0
activity	0
of	0
folic	1
acid	2
after	0
drug	0
induces	0
SLE	3
(	0
folic	1
acid	2
and	0
epilepsy	3
)	0

0BJECTIVE	0
:	0
To	0
study	0
the	0
effect	0
of	0
folic	1
acid	2
-	0
containing	0
multivitamin	0
supplementation	0
in	0
epileptic	3
women	0
before	0
and	0
during	0
pregnancy	0
in	0
order	0
to	0
determine	0
the	0
rate	0
of	0
structural	0
birth	3
defects	4
and	0
epilepsy	3
-	0
related	0
side	0
effects	0
.	0

STUDY	0
DESIGN	0
:	0
First	0
a	0
randomised	0
trial	0
,	0
later	0
periconception	0
care	0
including	0
in	0
total	0
12225	0
females	0
.	0

RESULTS	0
:	0
0f	0
60	0
epileptic	3
women	0
with	0
periconceptional	0
folic	1
acid	2
(	0
0	0
.	0
8	0
mg	0
)	0
-	0
containing	0
multivitamin	0
supplementation	0
,	0
no	0
one	0
developed	0
epilepsy	3
-	0
related	0
side	0
effects	0
during	0
the	0
periconception	0
period	0
.	0

0ne	0
epileptic	3
woman	0
delivered	0
a	0
newborn	0
with	0
cleft	3
lip	4
and	4
palate	4
.	0

Another	0
patient	0
exhibited	0
with	0
a	0
cluster	0
of	0
seizures	3
after	0
the	0
periconception	0
period	0
using	0
another	0
multivitamin	0
.	0

This	0
22	0
-	0
year	0
-	0
old	0
epileptic	3
woman	0
was	0
treated	0
continuously	0
by	0
carbamazepine	1
and	0
a	0
folic	1
acid	2
(	0
1	0
mg	0
)	0
-	0
containing	0
multivitamin	0
from	0
the	0
20th	0
week	0
of	0
gestation	0
.	0

She	0
developed	0
status	3
epilepticus	4
and	0
later	0
symptoms	0
of	0
systemic	3
lupus	4
erythematodes	4
.	0

Her	0
pregnancy	0
ended	0
with	0
stillbirth	3
.	0

C0NCLUSI0NS	0
:	0
The	0
epileptic	3
pregnant	0
patient	0
'	0
s	0
autoimmune	3
disease	4
(	0
probably	0
drug	0
-	0
induced	0
lupus	3
)	0
could	0
damage	0
the	0
blood	0
-	0
brain	0
barrier	0
,	0
therefore	0
the	0
therapeutic	0
dose	0
(	0
>	0
or	0
=	0
1	0
mg	0
)	0
of	0
folic	1
acid	2
triggered	0
a	0
cluster	0
of	0
seizures	3
.	0

Physiological	0
dose	0
(	0
<	0
1	0
mg	0
)	0
of	0
folic	1
acid	2
both	0
in	0
healthy	0
and	0
60	0
epileptic	3
women	0
,	0
all	0
without	0
any	0
autoimmune	3
disease	4
,	0
did	0
not	0
increase	0
the	0
risk	0
for	0
epileptic	3
seizures	4
.	0

Stroke	3
and	0
cocaine	1
or	0
amphetamine	1
use	0
.	0

The	0
association	0
of	0
cocaine	1
and	0
amphetamine	1
use	0
with	0
hemorrhagic	0
and	0
ischemic	3
stroke	3
is	0
based	0
almost	0
solely	0
on	0
data	0
from	0
case	0
series	0
.	0

The	0
limited	0
number	0
of	0
epidemiologic	0
studies	0
of	0
stroke	3
and	0
use	0
of	0
cocaine	1
and	0
/	0
or	0
amphetamine	1
have	0
been	0
done	0
in	0
settings	0
that	0
serve	0
mostly	0
the	0
poor	0
and	0
/	0
or	0
minorities	0
.	0

This	0
case	0
-	0
control	0
study	0
was	0
conducted	0
in	0
the	0
defined	0
population	0
comprising	0
members	0
of	0
Kaiser	0
Permanente	0
of	0
Northern	0
and	0
Southern	0
California	0
.	0

We	0
attempted	0
to	0
identify	0
all	0
incident	0
strokes	3
in	0
women	0
ages	0
15	0
-	0
44	0
years	0
during	0
a	0
3	0
-	0
year	0
period	0
using	0
hospital	0
admission	0
and	0
discharge	0
records	0
,	0
emergency	0
department	0
logs	0
,	0
and	0
payment	0
requests	0
for	0
out	0
-	0
of	0
-	0
plan	0
hospitalizations	0
.	0

We	0
selected	0
controls	0
,	0
matched	0
on	0
age	0
and	0
facility	0
of	0
usual	0
care	0
,	0
at	0
random	0
from	0
healthy	0
members	0
of	0
the	0
health	0
plan	0
.	0

We	0
obtained	0
information	0
in	0
face	0
-	0
to	0
-	0
face	0
interviews	0
.	0

There	0
were	0
347	0
confirmed	0
stroke	3
cases	0
and	0
1	0
,	0
021	0
controls	0
.	0

The	0
univariate	0
matched	0
odds	0
ratio	0
for	0
stroke	3
in	0
women	0
who	0
admitted	0
to	0
using	0
cocaine	1
and	0
/	0
or	0
amphetamine	1
was	0
8	0
.	0
5	0
(	0
95	0
%	0
confidence	0
interval	0
=	0
3	0
.	0
6	0
-	0
20	0
.	0
0	0
)	0
.	0

After	0
further	0
adjustment	0
for	0
potential	0
confounders	0
,	0
the	0
odds	0
ratio	0
in	0
women	0
who	0
reported	0
using	0
cocaine	1
and	0
/	0
or	0
amphetamine	1
was	0
7	0
.	0
0	0
(	0
95	0
%	0
confidence	0
interval	0
=	0
2	0
.	0
8	0
-	0
17	0
.	0
9	0
)	0
.	0

The	0
use	0
of	0
cocaine	1
and	0
/	0
or	0
amphetamine	1
is	0
a	0
strong	0
risk	0
factor	0
for	0
stroke	3
in	0
this	0
socioeconomically	0
heterogeneous	0
,	0
insured	0
urban	0
population	0
.	0

Acute	3
renal	4
failure	4
subsequent	0
to	0
the	0
administration	0
of	0
rifampicin	1
.	0

A	0
follow	0
-	0
up	0
study	0
of	0
cases	0
reported	0
earlier	0
.	0

A	0
clinical	0
presentation	0
is	0
made	0
of	0
a	0
2	0
-	0
3	0
year	0
follow	0
-	0
up	0
of	0
six	0
cases	0
of	0
acute	3
renal	4
failure	4
that	0
have	0
been	0
reported	0
earlier	0
.	0

The	0
patients	0
had	0
developed	0
transient	0
renal	3
failure	4
after	0
the	0
intermittent	0
administration	0
of	0
rifampicin	1
.	0

The	0
stage	0
of	0
olig	0
-	0
anuria	3
lasted	0
for	0
1	0
-	0
3	0
weeks	0
,	0
and	0
five	0
of	0
the	0
patients	0
were	0
treated	0
by	0
hemodialysis	0
.	0

Two	0
of	0
the	0
patients	0
died	0
due	0
to	0
unrelated	0
causes	0
during	0
the	0
follow	0
-	0
up	0
period	0
.	0

The	0
four	0
patients	0
re	0
-	0
examined	0
were	0
clinically	0
cured	0
.	0

Pathologic	0
findings	0
by	0
light	0
microscopy	0
and	0
immunofluorescence	0
at	0
biopsy	0
were	0
scarce	0
.	0

Nothing	0
abnormal	0
was	0
seen	0
by	0
electron	0
microscopy	0
in	0
two	0
of	0
the	0
cases	0
studied	0
.	0

Renal	0
function	0
was	0
normal	0
.	0

In	0
three	0
cases	0
the	0
excretion	0
at	0
131I	0
-	0
hippuran	0
renography	0
was	0
slightly	0
slowed	0
.	0

Although	0
in	0
the	0
acute	0
stage	0
the	0
renal	3
lesions	4
histologically	0
appeared	0
toxic	0
,	0
evidence	0
suggestive	0
of	0
an	0
immunological	0
mechanism	0
cannot	0
be	0
excluded	0
.	0

Chronic	0
effects	0
of	0
a	0
novel	0
synthetic	0
anthracycline	1
derivative	0
(	0
SM	1
-	2
5887	2
)	0
on	0
normal	0
heart	0
and	0
doxorubicin	1
-	0
induced	0
cardiomyopathy	3
in	0
beagle	0
dogs	0
.	0

This	0
study	0
was	0
designed	0
to	0
investigate	0
the	0
chronic	0
cardiotoxic	3
potential	0
of	0
SM	1
-	2
5887	2
and	0
a	0
possible	0
deteriorating	0
effect	0
of	0
SM	1
-	2
5887	2
on	0
low	0
-	0
grade	0
cardiotoxicity	3
pre	0
-	0
induced	0
by	0
doxorubicin	1
in	0
beagle	0
dogs	0
.	0

In	0
the	0
chronic	0
treatment	0
,	0
beagle	0
dogs	0
of	0
each	0
sex	0
were	0
given	0
intravenously	0
once	0
every	0
3	0
weeks	0
,	0
either	0
a	0
sublethal	0
dose	0
of	0
doxorubicin	1
(	0
1	0
.	0
5	0
mg	0
/	0
kg	0
)	0
or	0
SM	1
-	2
5887	2
(	0
2	0
.	0
5	0
mg	0
/	0
kg	0
)	0
.	0

The	0
experiment	0
was	0
terminated	0
3	0
weeks	0
after	0
the	0
ninth	0
dosing	0
.	0

Animals	0
which	0
received	0
over	0
six	0
courses	0
of	0
doxorubicin	1
demonstrated	0
the	0
electrocardiogram	0
(	0
ECG	0
)	0
changes	0
,	0
decrease	0
of	0
blood	0
pressure	0
and	0
high	0
-	0
grade	0
histopathological	0
cardiomyopathy	3
,	0
while	0
animals	0
which	0
were	0
terminally	0
sacrificed	0
after	0
the	0
SM	1
-	2
5887	2
administration	0
did	0
not	0
show	0
any	0
changes	0
in	0
ECG	0
,	0
blood	0
pressure	0
and	0
histopathological	0
examinations	0
.	0

To	0
examine	0
a	0
possibly	0
deteriorating	0
cardiotoxic	3
effect	0
of	0
SM	1
-	2
5887	2
,	0
low	0
-	0
grade	0
cardiomyopathy	3
was	0
induced	0
in	0
dogs	0
by	0
four	0
courses	0
of	0
doxorubicin	1
(	0
1	0
.	0
5	0
mg	0
/	0
kg	0
)	0
.	0

Nine	0
weeks	0
after	0
pre	0
-	0
treatment	0
,	0
dogs	0
were	0
given	0
four	0
courses	0
of	0
either	0
doxorubicin	1
(	0
1	0
.	0
5	0
mg	0
/	0
kg	0
)	0
or	0
SM	1
-	2
5887	2
(	0
2	0
.	0
5	0
mg	0
/	0
kg	0
)	0
once	0
every	0
3	0
weeks	0
.	0

The	0
low	0
-	0
grade	0
cardiotoxic	3
changes	0
were	0
enhanced	0
by	0
the	0
additional	0
doxorubicin	1
treatment	0
.	0

0n	0
the	0
contrary	0
,	0
the	0
SM	1
-	2
5887	2
treatment	0
did	0
not	0
progress	0
the	0
grade	0
of	0
cardiomyopathy	3
.	0

In	0
conclusion	0
,	0
SM	1
-	2
5887	2
does	0
not	0
have	0
any	0
potential	0
of	0
chronic	0
cardiotoxicity	3
and	0
deteriorating	0
effect	0
on	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
in	0
dogs	0
.	0

Risk	0
for	0
valvular	3
heart	4
disease	4
among	0
users	0
of	0
fenfluramine	1
and	0
dexfenfluramine	1
who	0
underwent	0
echocardiography	0
before	0
use	0
of	0
medication	0
.	0

BACKGR0UND	0
:	0
Because	0
uncontrolled	0
echocardiographic	0
surveys	0
suggested	0
that	0
up	0
to	0
30	0
%	0
to	0
38	0
%	0
of	0
users	0
of	0
fenfluramine	1
and	0
dexfenfluramine	1
had	0
valvular	3
disease	4
,	0
these	0
drugs	0
were	0
withdrawn	0
from	0
the	0
market	0
.	0

0BJECTIVE	0
:	0
To	0
determine	0
the	0
risk	0
for	0
new	0
or	0
worsening	0
valvular	3
abnormalities	4
among	0
users	0
of	0
fenfluramine	1
or	0
dexfenfluramine	1
who	0
underwent	0
echocardiography	0
before	0
they	0
began	0
to	0
take	0
these	0
medications	0
.	0

DESIGN	0
:	0
Cohort	0
study	0
.	0

SETTING	0
:	0
Academic	0
primary	0
care	0
practices	0
.	0

PATIENTS	0
:	0
46	0
patients	0
who	0
used	0
fenfluramine	1
or	0
dexfenfluramine	1
for	0
14	0
days	0
or	0
more	0
and	0
had	0
echocardiograms	0
obtained	0
before	0
therapy	0
.	0

MEASUREMENTS	0
:	0
Follow	0
-	0
up	0
echocardiography	0
.	0

The	0
primary	0
outcome	0
was	0
new	0
or	0
worsening	0
valvulopathy	3
,	0
defined	0
as	0
progression	0
of	0
either	0
aortic	3
or	4
mitral	4
regurgitation	4
by	0
at	0
least	0
one	0
degree	0
of	0
severity	0
and	0
disease	0
that	0
met	0
U	0
.	0
S	0
.	0

Food	0
and	0
Drug	0
Administration	0
criteria	0
(	0
at	0
least	0
mild	0
aortic	3
regurgitation	4
or	0
moderate	0
mitral	3
regurgitation	4
)	0
.	0

RESULTS	0
:	0
Two	0
patients	0
(	0
4	0
.	0
3	0
%	0
[	0
95	0
%	0
CI	0
,	0
0	0
.	0
6	0
%	0
to	0
14	0
.	0
8	0
%	0
]	0
)	0
receiving	0
fenfluramine	1
-	0
phentermine	1
developed	0
valvular	3
heart	4
disease	4
.	0

0ne	0
had	0
baseline	0
bicuspid	3
aortic	4
valve	4
and	0
mild	0
aortic	3
regurgitation	4
that	0
progressed	0
to	0
moderate	0
regurgitation	0
.	0

The	0
second	0
patient	0
developed	0
new	0
moderate	0
aortic	3
insufficiency	4
.	0

C0NCLUSI0N	0
:	0
Users	0
of	0
diet	0
medications	0
are	0
at	0
risk	0
for	0
valvular	3
heart	4
disease	4
.	0

However	0
,	0
the	0
incidence	0
may	0
be	0
lower	0
than	0
that	0
reported	0
previously	0
.	0

Therapeutic	0
drug	0
monitoring	0
of	0
tobramycin	1
:	0
once	0
-	0
daily	0
versus	0
twice	0
-	0
daily	0
dosage	0
schedules	0
.	0

0BJECTIVE	0
:	0
To	0
evaluate	0
the	0
effect	0
of	0
dosage	0
regimen	0
(	0
once	0
-	0
daily	0
vs	0
.	0
twice	0
-	0
daily	0
)	0
of	0
tobramicyn	1
on	0
steady	0
-	0
state	0
serum	0
concentrations	0
and	0
toxicity	3
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
Patients	0
undergoing	0
treatment	0
with	0
i	0
.	0
v	0
.	0
tobramycin	1
(	0
4	0
mg	0
/	0
kg	0
/	0
day	0
)	0
were	0
randomised	0
to	0
two	0
groups	0
.	0

Group	0
0D	0
(	0
n	0
=	0
22	0
)	0
received	0
a	0
once	0
-	0
daily	0
dose	0
of	0
tobramycin	1
and	0
group	0
TD	0
(	0
n	0
=	0
21	0
)	0
received	0
the	0
same	0
dose	0
divided	0
into	0
two	0
doses	0
daily	0
.	0

Tobramycin	1
serum	0
concentrations	0
(	0
peak	0
and	0
trough	0
)	0
were	0
measured	0
by	0
enzyme	0
multiplied	0
immunoassay	0
.	0

The	0
renal	0
and	0
auditory	0
functions	0
of	0
the	0
patients	0
were	0
monitored	0
before	0
,	0
during	0
and	0
immediately	0
after	0
treatment	0
.	0

RESULTS	0
:	0
The	0
two	0
groups	0
were	0
comparable	0
with	0
respect	0
to	0
sex	0
,	0
age	0
,	0
body	0
weight	0
and	0
renal	0
function	0
.	0

No	0
statistically	0
significant	0
differences	0
were	0
found	0
in	0
mean	0
daily	0
dose	0
,	0
duration	0
of	0
treatment	0
,	0
or	0
cumulative	0
dose	0
.	0

Trough	0
concentrations	0
were	0
<	0
2	0
g	0
/	0
ml	0
in	0
the	0
two	0
groups	0
(	0
100	0
%	0
)	0
.	0

Peak	0
concentrations	0
were	0
>	0
6	0
microg	0
/	0
ml	0
in	0
100	0
%	0
of	0
the	0
0D	0
group	0
and	0
in	0
67	0
%	0
of	0
the	0
TD	0
group	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

Mean	0
peak	0
concentrations	0
were	0
markedly	0
different	0
:	0
11	0
.	0
00	0
+	0
/	0
-	0
2	0
.	0
89	0
microg	0
/	0
ml	0
in	0
0D	0
vs	0
.	0
6	0
.	0
53	0
+	0
/	0
-	0
1	0
.	0
45	0
microg	0
/	0
ml	0
in	0
TD	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

The	0
pharmacokinetics	0
parameters	0
were	0
:	0
Ke	0
,	0
(	0
0	0
.	0
15	0
+	0
/	0
-	0
0	0
.	0
03	0
/	0
h	0
in	0
0D	0
vs	0
.	0
0	0
.	0
24	0
+	0
/	0
-	0
0	0
.	0
06	0
/	0
h	0
in	0
TD	0
)	0
,	0
t1	0
/	0
2	0
,	0
(	0
4	0
.	0
95	0
+	0
/	0
-	0
1	0
.	0
41	0
h	0
in	0
0D	0
vs	0
.	0
3	0
.	0
07	0
+	0
/	0
-	0
0	0
.	0
71	0
h	0
in	0
TD	0
)	0
,	0
Vd	0
(	0
0	0
.	0
35	0
+	0
/	0
-	0
0	0
.	0
11	0
l	0
/	0
kg	0
in	0
0D	0
vs	0
.	0
0	0
.	0
33	0
+	0
/	0
-	0
0	0
.	0
09	0
l	0
/	0
kg	0
in	0
TD	0
)	0
,	0
Cl	0
(	0
0	0
.	0
86	0
+	0
/	0
-	0
0	0
.	0
29	0
ml	0
/	0
min	0
/	0
kg	0
in	0
0D	0
vs	0
.	0
1	0
.	0
28	0
+	0
/	0
-	0
0	0
.	0
33	0
ml	0
/	0
min	0
/	0
kg	0
in	0
TD	0
)	0
.	0

Increased	0
serum	0
creatinine	1
was	0
observed	0
in	0
73	0
%	0
of	0
patients	0
in	0
0D	0
versus	0
57	0
%	0
of	0
patients	0
in	0
TD	0
,	0
without	0
evidence	0
of	0
nephrotoxicity	3
.	0

In	0
TD	0
group	0
,	0
three	0
patients	0
developed	0
decreased	3
auditory	4
function	4
,	0
of	0
which	0
one	0
presented	0
with	0
an	0
auditory	3
loss	4
of	0
-	0
30	0
dB	0
,	0
whereas	0
in	0
the	0
0D	0
group	0
only	0
one	0
patient	0
presented	0
decreased	3
auditory	4
function	4
.	0

C0NCLUSI0N	0
:	0
This	0
small	0
study	0
suggests	0
that	0
a	0
once	0
-	0
daily	0
dosing	0
regimen	0
of	0
tobramycin	1
is	0
at	0
least	0
as	0
effective	0
as	0
and	0
is	0
no	0
more	0
and	0
possibly	0
less	0
toxic	0
than	0
the	0
twice	0
-	0
daily	0
regimen	0
.	0

Using	0
a	0
single	0
-	0
dose	0
therapy	0
,	0
peak	0
concentration	0
determination	0
is	0
not	0
necessary	0
,	0
only	0
trough	0
samples	0
should	0
be	0
monitored	0
to	0
ensure	0
levels	0
below	0
2	0
microg	0
/	0
ml	0
.	0

Enhanced	0
bradycardia	3
induced	0
by	0
beta	0
-	0
adrenoceptor	0
antagonists	0
in	0
rats	0
pretreated	0
with	0
isoniazid	1
.	0

High	0
doses	0
of	0
isoniazid	1
increase	0
hypotension	3
induced	0
by	0
vasodilators	0
and	0
change	0
the	0
accompanying	0
reflex	0
tachycardia	3
to	0
bradycardia	3
,	0
an	0
interaction	0
attributed	0
to	0
decreased	0
synthesis	0
of	0
brain	0
gamma	1
-	2
aminobutyric	2
acid	2
(	0
GABA	1
)	0
.	0

In	0
the	0
present	0
study	0
,	0
the	0
possible	0
enhancement	0
by	0
isoniazid	1
of	0
bradycardia	3
induced	0
by	0
beta	0
-	0
adrenoceptor	0
antagonists	0
was	0
determined	0
in	0
rats	0
anaesthetised	0
with	0
chloralose	1
-	0
urethane	1
.	0

Isoniazid	1
significantly	0
increased	0
bradycardia	3
after	0
propranolol	1
,	0
pindolol	1
,	0
labetalol	1
and	0
atenolol	1
,	0
as	0
well	0
as	0
after	0
clonidine	1
,	0
but	0
not	0
after	0
hexamethonium	1
or	0
carbachol	1
.	0

Enhancement	0
was	0
not	0
observed	0
in	0
rats	0
pretreated	0
with	0
methylatropine	1
or	0
previously	0
vagotomised	0
.	0

These	0
results	0
are	0
compatible	0
with	0
interference	0
by	0
isoniazid	1
with	0
GABAergic	0
inhibition	0
of	0
cardiac	0
parasympathetic	0
tone	0
.	0

Such	0
interference	0
could	0
be	0
exerted	0
centrally	0
,	0
possibly	0
at	0
the	0
nucleus	0
ambiguus	0
,	0
or	0
peripherally	0
at	0
the	0
sinus	0
node	0
.	0

Structural	3
and	4
functional	4
impairment	4
of	4
mitochondria	4
in	0
adriamycin	1
-	0
induced	0
cardiomyopathy	3
in	0
mice	0
:	0
suppression	0
of	0
cytochrome	0
c	0
oxidase	0
II	0
gene	0
expression	0
.	0

The	0
use	0
of	0
adriamycin	1
(	0
ADR	1
)	0
in	0
cancer	3
chemotherapy	0
has	0
been	0
limited	0
due	0
to	0
its	0
cumulative	0
cardiovascular	3
toxicity	4
.	0

Earlier	0
observations	0
that	0
ADR	1
interacts	0
with	0
mitochondrial	0
cytochrome	0
c	0
oxidase	0
(	0
C0X	0
)	0
and	0
suppresses	0
its	0
enzyme	0
activity	0
led	0
us	0
to	0
investigate	0
ADR	1
'	0
s	0
action	0
on	0
the	0
cardiovascular	0
functions	0
and	0
heart	0
mitochondrial	0
morphology	0
in	0
Balb	0
-	0
c	0
mice	0
i	0
.	0
p	0
.	0
treated	0
with	0
ADR	1
for	0
several	0
weeks	0
.	0

At	0
various	0
times	0
during	0
treatment	0
,	0
the	0
animals	0
were	0
assessed	0
for	0
cardiovascular	0
functions	0
by	0
electrocardiography	0
and	0
for	0
heart	0
tissue	0
damage	0
by	0
electron	0
microscopy	0
.	0

In	0
parallel	0
,	0
total	0
RNA	0
was	0
extracted	0
from	0
samples	0
of	0
dissected	0
heart	0
and	0
analyzed	0
by	0
Northern	0
blot	0
hybridization	0
to	0
determine	0
the	0
steady	0
-	0
state	0
level	0
of	0
three	0
RNA	0
transcripts	0
encoded	0
by	0
the	0
C0XII	0
,	0
C0XIII	0
,	0
and	0
C0XIV	0
genes	0
.	0

Similarly	0
,	0
samples	0
obtained	0
from	0
the	0
liver	0
of	0
the	0
same	0
animals	0
were	0
analyzed	0
for	0
comparative	0
studies	0
.	0

0ur	0
results	0
indicated	0
that	0
1	0
)	0
treatment	0
of	0
mice	0
with	0
ADR	1
caused	0
cardiovascular	3
arrhythmias	4
characterized	0
by	0
bradycardia	3
,	0
extension	0
of	0
ventricular	0
depolarization	0
time	0
(	0
tQRS	0
)	0
,	0
and	0
failure	0
of	0
QRS	0
at	0
high	0
concentrations	0
(	0
10	0
-	0
14	0
mg	0
/	0
kg	0
body	0
weight	0
cumulative	0
dose	0
)	0
;	0
2	0
)	0
the	0
heart	0
mitochondria	0
underwent	0
swelling	3
,	0
fusion	0
,	0
dissolution	0
,	0
and	0
/	0
or	0
disruption	0
of	0
mitochondrial	0
cristae	0
after	0
several	0
weeks	0
of	0
treatment	0
.	0

Such	0
abnormalities	0
were	0
not	0
observed	0
in	0
the	0
mitochondria	0
of	0
liver	0
tissue	0
;	0
and	0
3	0
)	0
among	0
the	0
three	0
genes	0
of	0
C0X	0
enzyme	0
examined	0
,	0
only	0
C0XII	0
gene	0
expression	0
was	0
suppressed	0
by	0
ADR	1
treatment	0
,	0
mainly	0
after	0
8	0
weeks	0
in	0
both	0
heart	0
and	0
liver	0
.	0

Knowing	0
that	0
heart	0
mitochondria	0
represent	0
almost	0
40	0
%	0
of	0
heart	0
muscle	0
by	0
weight	0
,	0
we	0
conclude	0
that	0
the	0
deteriorating	0
effects	0
of	0
ADR	1
on	0
cardiovascular	0
function	0
involve	0
mitochondrial	3
structural	4
and	4
functional	4
impairment	4
.	0

Torsade	3
de	4
pointes	4
ventricular	3
tachycardia	4
during	0
low	0
dose	0
intermittent	0
dobutamine	1
treatment	0
in	0
a	0
patient	0
with	0
dilated	3
cardiomyopathy	4
and	0
congestive	3
heart	4
failure	4
.	0

The	0
authors	0
describe	0
the	0
case	0
of	0
a	0
56	0
-	0
year	0
-	0
old	0
woman	0
with	0
chronic	0
,	0
severe	0
heart	3
failure	4
secondary	0
to	0
dilated	3
cardiomyopathy	4
and	0
absence	0
of	0
significant	0
ventricular	3
arrhythmias	4
who	0
developed	0
QT	3
prolongation	4
and	0
torsade	3
de	4
pointes	4
ventricular	3
tachycardia	4
during	0
one	0
cycle	0
of	0
intermittent	0
low	0
dose	0
(	0
2	0
.	0
5	0
mcg	0
/	0
kg	0
per	0
min	0
)	0
dobutamine	1
.	0

This	0
report	0
of	0
torsade	3
de	4
pointes	4
ventricular	3
tachycardia	4
during	0
intermittent	0
dobutamine	1
supports	0
the	0
hypothesis	0
that	0
unpredictable	0
fatal	0
arrhythmias	3
may	0
occur	0
even	0
with	0
low	0
doses	0
and	0
in	0
patients	0
with	0
no	0
history	0
of	0
significant	0
rhythm	0
disturbances	0
.	0

The	0
mechanisms	0
of	0
proarrhythmic	0
effects	0
of	0
Dubutamine	1
are	0
discussed	0
.	0

Positive	0
skin	0
tests	0
in	0
late	0
reactions	0
to	0
radiographic	0
contrast	1
media	2
.	0

In	0
the	0
last	0
few	0
years	0
delayed	0
reactions	0
several	0
hours	0
after	0
the	0
injection	0
of	0
radiographic	0
and	0
contrast	1
materials	2
(	0
PRC	1
)	0
have	0
been	0
described	0
with	0
increasing	0
frequency	0
.	0

The	0
authors	0
report	0
two	0
observations	0
on	0
patients	0
with	0
delayed	0
reactions	0
in	0
whom	0
intradermoreactions	0
(	0
IDR	0
)	0
and	0
patch	0
tests	0
to	0
a	0
series	0
of	0
ionic	0
and	0
non	0
ionic	0
PRC	1
were	0
studied	0
.	0

After	0
angiography	0
by	0
the	0
venous	0
route	0
in	0
patient	0
n	0
degree	0
1	0
a	0
biphasic	0
reaction	0
with	0
an	0
immediate	0
reaction	0
(	0
dyspnea	3
,	0
loss	3
of	4
consciousness	4
)	0
and	0
delayed	0
macro	3
-	4
papular	4
rash	4
appeared	0
,	0
whilst	0
patient	0
n	0
degree	0
2	0
developed	0
a	0
generalised	0
sensation	0
of	0
heat	0
,	0
persistent	0
pain	3
at	0
the	0
site	0
of	0
injection	0
immediately	0
and	0
a	0
generalised	0
macro	0
-	0
papular	0
reaction	0
after	0
24	0
hours	0
.	0

The	0
skin	0
tests	0
revealed	0
positive	0
delayed	0
reactions	0
of	0
24	0
hours	0
and	0
48	0
hours	0
by	0
IDR	0
and	0
patch	0
tests	0
to	0
only	0
some	0
PRC	1
with	0
common	0
chains	0
in	0
their	0
structures	0
.	0

The	0
positive	0
skin	0
tests	0
are	0
in	0
favour	0
of	0
immunological	0
reactions	0
and	0
may	0
help	0
in	0
diagnosis	0
of	0
allergy	3
in	0
the	0
patients	0
.	0

Risk	0
of	0
transient	0
hyperammonemic	3
encephalopathy	4
in	0
cancer	3
patients	0
who	0
received	0
continuous	0
infusion	0
of	0
5	1
-	2
fluorouracil	2
with	0
the	0
complication	0
of	0
dehydration	3
and	0
infection	3
.	0

From	0
1986	0
to	0
1998	0
,	0
29	0
cancer	3
patients	0
who	0
had	0
32	0
episodes	0
of	0
transient	0
hyperammonemic	3
encephalopathy	4
related	0
to	0
continuous	0
infusion	0
of	0
5	1
-	2
fluorouracil	2
(	0
5	1
-	2
FU	2
)	0
were	0
identified	0
.	0

None	0
of	0
the	0
patients	0
had	0
decompensated	0
liver	3
disease	4
.	0

0nset	0
of	0
hyperammonemic	3
encephalopathy	4
varied	0
from	0
0	0
.	0
5	0
to	0
5	0
days	0
(	0
mean	0
:	0
2	0
.	0
6	0
+	0
/	0
-	0
1	0
.	0
3	0
days	0
)	0
after	0
the	0
initiation	0
of	0
chemotherapy	0
.	0

Plasma	0
ammonium	1
level	0
ranged	0
from	0
248	0
to	0
2387	0
microg	0
%	0
(	0
mean	0
:	0
626	0
+	0
/	0
-	0
431	0
microg	0
%	0
)	0
.	0

Among	0
the	0
32	0
episodes	0
,	0
26	0
(	0
81	0
%	0
)	0
had	0
various	0
degrees	0
of	0
azotemia	3
,	0
18	0
(	0
56	0
%	0
)	0
occurred	0
during	0
bacterial	3
infections	4
and	0
14	0
(	0
44	0
%	0
)	0
without	0
infection	3
occurred	0
during	0
periods	0
of	0
dehydration	3
.	0

Higher	0
plasma	0
ammonium	1
levels	0
and	0
more	0
rapid	0
onset	0
of	0
hyperammonemia	3
were	0
seen	0
in	0
18	0
patients	0
with	0
bacterial	3
infections	4
(	0
p	0
=	0
0	0
.	0
003	0
and	0
0	0
.	0
0006	0
,	0
respectively	0
)	0
and	0
in	0
nine	0
patients	0
receiving	0
high	0
daily	0
doses	0
(	0
2600	0
or	0
1800	0
mg	0
/	0
m2	0
)	0
of	0
5	1
-	2
FU	2
(	0
p	0
=	0
0	0
.	0
0001	0
and	0
<	0
0	0
.	0
0001	0
,	0
respectively	0
)	0
.	0

In	0
25	0
out	0
of	0
32	0
episodes	0
(	0
78	0
%	0
)	0
,	0
plasma	0
ammonium	1
levels	0
and	0
mental	0
status	0
returned	0
to	0
normal	0
within	0
2	0
days	0
after	0
adequate	0
management	0
.	0

In	0
conclusion	0
,	0
hyperammonemic	3
encephalopathy	4
can	0
occur	0
in	0
patients	0
receiving	0
continuous	0
infusion	0
of	0
5	1
-	2
FU	2
.	0

Azotemia	3
,	0
body	0
fluid	0
insufficiency	0
and	0
bacterial	3
infections	4
were	0
frequently	0
found	0
in	0
these	0
patients	0
.	0

It	0
is	0
therefore	0
important	0
to	0
recognize	0
this	0
condition	0
in	0
patients	0
receiving	0
continuous	0
infusion	0
of	0
5	1
-	2
FU	2
.	0

The	0
effects	0
of	0
quinine	1
and	0
4	1
-	2
aminopyridine	2
on	0
conditioned	0
place	0
preference	0
and	0
changes	0
in	0
motor	0
activity	0
induced	0
by	0
morphine	1
in	0
rats	0
.	0

1	0
.	0

The	0
effects	0
of	0
two	0
unselective	0
potassium	1
(	0
K	1
(	0
+	0
)	0
-	0
)	0
channel	0
blockers	0
,	0
quinine	1
(	0
12	0
.	0
5	0
,	0
25	0
and	0
50	0
mg	0
/	0
kg	0
)	0
and	0
4	1
-	2
aminopyridine	2
(	0
1	0
and	0
2	0
mg	0
/	0
kg	0
)	0
,	0
on	0
conditioned	0
place	0
preference	0
and	0
biphasic	0
changes	0
in	0
motor	0
activity	0
induced	0
by	0
morphine	1
(	0
10	0
mg	0
/	0
kg	0
)	0
were	0
tested	0
in	0
Wistar	0
rats	0
.	0

Quinine	1
is	0
known	0
to	0
block	0
voltage	0
-	0
,	0
calcium	1
-	0
and	0
ATP	1
-	0
sensitive	0
K	1
(	0
+	0
)	0
-	0
channels	0
while	0
4	1
-	2
aminopyridine	2
is	0
known	0
to	0
block	0
voltage	0
-	0
sensitive	0
K	1
(	0
+	0
)	0
-	0
channels	0
.	0

2	0
.	0

In	0
the	0
counterbalanced	0
method	0
,	0
quinine	1
attenuated	0
morphine	1
-	0
induced	0
place	0
preference	0
,	0
whereas	0
4	1
-	2
aminopyridine	2
was	0
ineffective	0
.	0

In	0
the	0
motor	0
activity	0
test	0
measured	0
with	0
an	0
Animex	0
-	0
activity	0
meter	0
neither	0
of	0
the	0
K	1
(	0
+	0
)	0
-	0
channel	0
blockers	0
affected	0
morphine	1
-	0
induced	0
hypoactivity	3
,	0
but	0
both	0
K	1
(	0
+	0
)	0
-	0
channel	0
blockers	0
prevented	0
morphine	1
-	0
induced	0
secondary	0
hyperactivity	3
.	0

3	0
.	0

These	0
results	0
suggest	0
the	0
involvement	0
of	0
quinine	1
-	0
sensitive	0
but	0
not	0
4	1
-	2
aminopyridine	2
-	0
sensitive	0
K	1
(	0
+	0
)	0
-	0
channels	0
in	0
morphine	1
reward	0
.	0

It	0
is	0
also	0
suggested	0
that	0
the	0
blockade	0
of	0
K	1
(	0
+	0
)	0
-	0
channels	0
sensitive	0
to	0
these	0
blockers	0
is	0
not	0
sufficient	0
to	0
prevent	0
morphine	1
-	0
induced	0
hypoactivity	3
whereas	0
morphine	1
-	0
induced	0
hyperactivity	3
seems	0
to	0
be	0
connected	0
to	0
both	0
quinine	1
-	0
and	0
4	1
-	2
aminopyridine	2
-	0
sensitive	0
K	1
(	0
+	0
)	0
-	0
channels	0
.	0

Nociceptin	1
/	0
orphanin	1
FQ	2
and	0
nocistatin	1
on	0
learning	3
and	4
memory	4
impairment	4
induced	0
by	0
scopolamine	1
in	0
mice	0
.	0

1	0
.	0

Nociceptin	1
,	0
also	0
known	0
as	0
orphanin	1
FQ	2
,	0
is	0
an	0
endogenous	0
ligand	0
for	0
the	0
orphan	0
opioid	0
receptor	0
-	0
like	0
receptor	0
1	0
(	0
0RL1	0
)	0
and	0
involves	0
in	0
various	0
functions	0
in	0
the	0
central	0
nervous	0
system	0
(	0
CNS	0
)	0
.	0

0n	0
the	0
other	0
hand	0
,	0
nocistatin	1
is	0
recently	0
isolated	0
from	0
the	0
same	0
precursor	0
as	0
nociceptin	1
and	0
blocks	0
nociceptin	1
-	0
induced	0
allodynia	3
and	0
hyperalgesia	3
.	0

2	0
.	0

Although	0
0RL1	0
receptors	0
which	0
display	0
a	0
high	0
degree	0
of	0
sequence	0
homology	0
with	0
classical	0
opioid	0
receptors	0
are	0
abundant	0
in	0
the	0
hippocampus	0
,	0
little	0
is	0
known	0
regarding	0
their	0
role	0
in	0
learning	0
and	0
memory	0
.	0

3	0
.	0

The	0
present	0
study	0
was	0
designed	0
to	0
investigate	0
whether	0
nociceptin	1
/	0
orphanin	1
FQ	2
and	0
nocistatin	1
could	0
modulate	0
impairment	3
of	4
learning	4
and	4
memory	4
induced	0
by	0
scopolamine	1
,	0
a	0
muscarinic	0
cholinergic	0
receptor	0
antagonist	0
,	0
using	0
spontaneous	0
alternation	0
of	0
Y	0
-	0
maze	0
and	0
step	0
-	0
down	0
type	0
passive	0
avoidance	0
tasks	0
in	0
mice	0
.	0

4	0
.	0

While	0
nocistatin	1
(	0
0	0
.	0
5	0
-	0
5	0
.	0
0	0
nmol	0
mouse	0
-	0
1	0
,	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
administered	0
30	0
min	0
before	0
spontaneous	0
alternation	0
performance	0
or	0
the	0
training	0
session	0
of	0
the	0
passive	0
avoidance	0
task	0
,	0
had	0
no	0
effect	0
on	0
spontaneous	0
alternation	0
or	0
passive	0
avoidance	0
behaviours	0
,	0
a	0
lower	0
per	0
cent	0
alternation	0
and	0
shorter	0
median	0
step	0
-	0
down	0
latency	0
in	0
the	0
retention	0
test	0
were	0
obtained	0
in	0
nociceptin	1
(	0
1	0
.	0
5	0
and	0
/	0
or	0
5	0
.	0
0	0
nmol	0
mouse	0
-	0
1	0
,	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
-	0
treated	0
normal	0
mice	0
.	0

5	0
.	0

Administration	0
of	0
nocistatin	1
(	0
1	0
.	0
5	0
and	0
/	0
or	0
5	0
.	0
0	0
nmol	0
mouse	0
-	0
1	0
,	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
30	0
min	0
before	0
spontaneous	0
alternation	0
performance	0
or	0
the	0
training	0
session	0
of	0
the	0
passive	0
avoidance	0
task	0
,	0
attenuated	0
the	0
scopolamine	1
-	0
induced	0
impairment	0
of	0
spontaneous	0
alternation	0
and	0
passive	0
avoidance	0
behaviours	0
.	0

6	0
.	0

These	0
results	0
indicated	0
that	0
nocistatin	1
,	0
a	0
new	0
biologically	0
active	0
peptide	0
,	0
ameliorates	0
impairments	0
of	0
spontaneous	0
alternation	0
and	0
passive	0
avoidance	0
induced	0
by	0
scopolamine	1
,	0
and	0
suggested	0
that	0
these	0
peptides	0
play	0
opposite	0
roles	0
in	0
learning	0
and	0
memory	0
.	0

Meloxicam	1
-	0
induced	0
liver	3
toxicity	4
.	0

We	0
report	0
the	0
case	0
of	0
a	0
female	0
patient	0
with	0
rheumatoid	3
arthritis	4
who	0
developed	0
acute	0
cytolytic	0
hepatitis	3
due	0
to	0
meloxicam	1
.	0

Recently	0
introduced	0
in	0
Belgium	0
,	0
meloxicam	1
is	0
the	0
first	0
nonsteroidal	0
antiinflammatory	0
drug	0
with	0
selective	0
action	0
on	0
the	0
inducible	0
form	0
of	0
cyclooxygenase	0
2	0
.	0

The	0
acute	0
cytolytic	0
hepatitis	3
occurred	0
rapidly	0
after	0
meloxicam	1
administration	0
and	0
was	0
associated	0
with	0
the	0
development	0
of	0
antinuclear	0
antibodies	0
suggesting	0
a	0
hypersensitivity	3
mechanism	0
.	0

This	0
first	0
case	0
of	0
meloxicam	1
related	0
liver	3
toxicity	4
demonstrates	0
the	0
potential	0
of	0
this	0
drug	0
to	0
induce	0
hepatic	3
damage	4
.	0

Induction	0
of	0
apoptosis	0
by	0
remoxipride	1
metabolites	0
in	0
HL60	0
and	0
CD34	0
+	0
/	0
CD19	0
-	0
human	0
bone	0
marrow	0
progenitor	0
cells	0
:	0
potential	0
relevance	0
to	0
remoxipride	1
-	0
induced	0
aplastic	3
anemia	4
.	0

The	0
antipsychotic	0
agent	0
,	0
remoxipride	1
[	0
(	1
S	2
)	2
-	2
(	2
-	2
)	2
-	2
3	2
-	2
bromo	2
-	2
N	2
-	2
[	2
(	2
1	2
-	2
ethyl	2
-	2
2	2
-	2
pyrrolidinyl	2
)	2
methyl	2
]	2
-	2
2	2
,	2
6	2
-	2
dimethoxybenz	2
amide	2
]	0
has	0
been	0
associated	0
with	0
acquired	0
aplastic	3
anemia	4
.	0

We	0
have	0
examined	0
the	0
ability	0
of	0
remoxipride	1
,	0
three	0
pyrrolidine	1
ring	0
metabolites	0
and	0
five	0
aromatic	0
ring	0
metabolites	0
of	0
the	0
parent	0
compound	0
to	0
induce	0
apoptosis	0
in	0
HL60	0
cells	0
and	0
human	0
bone	0
marrow	0
progenitor	0
(	0
HBMP	0
)	0
cells	0
.	0

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

Apoptosis	0
was	0
assessed	0
by	0
fluorescence	0
microscopy	0
in	0
Hoechst	1
33342	2
-	0
and	0
propidium	1
iodide	2
stained	0
cell	0
samples	0
.	0

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

The	0
catechol	1
and	0
hydroquinone	1
metabolites	0
,	0
NCQ436	1
and	0
NCQ344	1
,	0
induced	0
apoptosis	0
in	0
HL60	0
and	0
HBMP	0
cells	0
in	0
a	0
time	0
-	0
and	0
concentration	0
dependent	0
manner	0
,	0
while	0
the	0
phenols	1
,	0
NCR181	0
,	0
FLA873	0
,	0
and	0
FLA797	1
,	0
and	0
the	0
derivatives	0
formed	0
by	0
oxidation	0
of	0
the	0
pyrrolidine	1
ring	0
,	0
FLA838	0
,	0
NCM001	0
,	0
and	0
NCL118	0
,	0
had	0
no	0
effect	0
.	0

No	0
necrosis	3
was	0
observed	0
in	0
cells	0
treated	0
with	0
NCQ436	1
but	0
NCQ344	1
had	0
a	0
biphasic	0
effect	0
in	0
both	0
cell	0
types	0
,	0
inducing	0
apoptosis	0
at	0
lower	0
concentrations	0
and	0
necrosis	3
at	0
higher	0
concentrations	0
.	0

These	0
data	0
show	0
that	0
the	0
catechol	1
and	0
hydroquinone	1
metabolites	0
of	0
remoxipride	1
have	0
direct	0
toxic	0
effects	0
in	0
HL60	0
and	0
HBMP	0
cells	0
,	0
leading	0
to	0
apoptosis	0
,	0
while	0
the	0
phenol	1
metabolites	0
were	0
inactive	0
.	0

Similarly	0
,	0
benzene	1
-	0
derived	0
catechol	1
and	0
hydroquinone	1
,	0
but	0
not	0
phenol	1
,	0
induce	0
apoptosis	0
in	0
HBMP	0
cells	0
[	0
Moran	0
et	0
al	0
.	0
,	0
Mol	0
.	0
Pharmacol	0
.	0
,	0
50	0
(	0
1996	0
)	0
610	0
-	0
615	0
]	0
.	0

We	0
propose	0
that	0
remoxipride	1
and	0
benzene	1
may	0
induce	0
aplastic	3
anemia	4
via	0
production	0
of	0
similar	0
reactive	0
metabolites	0
and	0
that	0
the	0
ability	0
of	0
NCQ436	1
and	0
NCQ344	1
to	0
induce	0
apoptosis	0
in	0
HBMP	0
cells	0
may	0
contribute	0
to	0
the	0
mechanism	0
underlying	0
acquired	0
aplastic	3
anemia	4
that	0
has	0
been	0
associated	0
with	0
remoxipride	1
.	0

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

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

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

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

7e	0
exhibits	0
a	0
high	0
reversal	0
of	0
catalepsy	3
induced	0
by	0
haloperidol	1
indicating	0
its	0
atypical	0
antipsychotic	0
nature	0
.	0

Sub	0
-	0
chronic	0
inhibition	0
of	0
nitric	1
-	2
oxide	2
synthesis	0
modifies	0
haloperidol	1
-	0
induced	0
catalepsy	3
and	0
the	0
number	0
of	0
NADPH	1
-	0
diaphorase	0
neurons	0
in	0
mice	0
.	0

RATI0NALE	0
:	0
NG	1
-	2
nitro	2
-	2
L	2
-	2
arginine	2
(	0
L	1
-	2
N0ARG	2
)	0
,	0
an	0
inhibitor	0
of	0
nitric	1
-	2
oxide	2
synthase	0
(	0
N0S	0
)	0
,	0
induces	0
catalepsy	3
in	0
mice	0
.	0

This	0
effect	0
undergoes	0
rapid	0
tolerance	0
,	0
showing	0
a	0
significant	0
decrease	0
after	0
2	0
days	0
of	0
sub	0
-	0
chronic	0
L	1
-	2
N0ARG	2
treatment	0
.	0

Nitric	1
oxide	2
(	0
N0	1
)	0
has	0
been	0
shown	0
to	0
influence	0
dopaminergic	0
neurotransmission	0
in	0
the	0
striatum	0
.	0

Neuroleptic	0
drugs	0
such	0
as	0
haloperidol	1
,	0
which	0
block	0
dopamine	1
receptors	0
,	0
also	0
cause	0
catalepsy	3
in	0
rodents	0
.	0

0BJECTIVES	0
:	0
To	0
investigate	0
the	0
effects	0
of	0
subchronic	0
L	1
-	2
N0ARG	2
treatment	0
in	0
haloperidol	1
-	0
induced	0
catalepsy	3
and	0
the	0
number	0
of	0
N0S	0
neurons	0
in	0
areas	0
related	0
to	0
motor	0
control	0
.	0

METH0DS	0
:	0
Male	0
albino	0
Swiss	0
mice	0
were	0
treated	0
sub	0
-	0
chronically	0
(	0
twice	0
a	0
day	0
for	0
4	0
days	0
)	0
with	0
L	1
-	2
N0ARG	2
(	0
40	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
or	0
haloperidol	1
(	0
1	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
.	0

Catalepsy	3
was	0
evaluated	0
at	0
the	0
beginning	0
and	0
the	0
end	0
of	0
the	0
treatments	0
.	0

Reduced	0
nicotinamide	1
adenine	2
dinucleotide	2
phosphate	2
-	0
diaphorase	0
(	0
NADPH	1
-	0
d	0
)	0
histochemistry	0
was	0
also	0
employed	0
to	0
visualize	0
N0S	0
as	0
an	0
index	0
of	0
enzyme	0
expression	0
in	0
mice	0
brain	0
regions	0
related	0
to	0
motor	0
control	0
.	0

RESULTS	0
:	0
L	1
-	2
N0ARG	2
sub	0
-	0
chronic	0
administration	0
produced	0
tolerance	0
of	0
L	1
-	2
N0ARG	2
and	0
of	0
haloperidol	1
-	0
induced	0
catalepsy	3
.	0

It	0
also	0
induced	0
an	0
increase	0
in	0
the	0
number	0
of	0
NADPH	1
-	0
d	0
-	0
positive	0
cells	0
in	0
the	0
dorsal	0
part	0
of	0
the	0
caudate	0
and	0
accumbens	0
nuclei	0
compared	0
with	0
haloperidol	1
and	0
in	0
the	0
pedunculopontine	0
tegmental	0
nucleus	0
compared	0
with	0
saline	0
.	0

In	0
contrast	0
,	0
there	0
was	0
a	0
decrease	0
in	0
NADPH	1
-	0
d	0
neuron	0
number	0
in	0
the	0
substantia	0
nigra	0
,	0
pars	0
compacta	0
in	0
both	0
haloperidol	1
-	0
treated	0
and	0
L	1
-	2
N0ARG	2
-	0
treated	0
animals	0
.	0

C0NCLUSI0NS	0
:	0
The	0
results	0
give	0
further	0
support	0
to	0
the	0
hypothesis	0
that	0
N0	1
plays	0
a	0
role	0
in	0
motor	0
behavior	0
control	0
and	0
suggest	0
that	0
it	0
may	0
take	0
part	0
in	0
the	0
synaptic	0
changes	0
produced	0
by	0
antipsychotic	0
treatment	0
.	0

Prolonged	0
left	3
ventricular	4
dysfunction	4
occurs	0
in	0
patients	0
with	0
coronary	3
artery	4
disease	4
after	0
both	0
dobutamine	1
and	0
exercise	0
induced	0
myocardial	3
ischaemia	4
.	0

0BJECTIVE	0
:	0
To	0
determine	0
whether	0
pharmacological	0
stress	0
leads	0
to	0
prolonged	0
but	0
reversible	0
left	3
ventricular	4
dysfunction	4
in	0
patients	0
with	0
coronary	3
artery	4
disease	4
,	0
similar	0
to	0
that	0
seen	0
after	0
exercise	0
.	0

DESIGN	0
:	0
A	0
randomised	0
crossover	0
study	0
of	0
recovery	0
time	0
of	0
systolic	0
and	0
diastolic	0
left	0
ventricular	0
function	0
after	0
exercise	0
and	0
dobutamine	1
induced	0
ischaemia	3
.	0

SUBJECTS	0
:	0
10	0
patients	0
with	0
stable	3
angina	4
,	0
angiographically	0
proven	0
coronary	3
artery	4
disease	4
,	0
and	0
normal	0
left	0
ventricular	0
function	0
.	0

INTERVENTI0NS	0
:	0
Treadmill	0
exercise	0
and	0
dobutamine	1
stress	0
were	0
performed	0
on	0
different	0
days	0
.	0

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

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

There	0
was	0
no	0
difference	0
in	0
the	0
maximum	0
double	0
product	0
(	0
p	0
=	0
0	0
.	0
53	0
)	0
or	0
ST	0
depression	3
(	0
p	0
=	0
0	0
.	0
63	0
)	0
with	0
either	0
form	0
of	0
stress	0
.	0

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

Regional	0
analysis	0
showed	0
a	0
reduction	0
in	0
the	0
worst	0
affected	0
segment	0
15	0
and	0
30	0
minutes	0
after	0
exercise	0
(	0
-	0
27	0
.	0
9	0
(	0
7	0
.	0
2	0
)	0
%	0
and	0
-	0
28	0
.	0
6	0
(	0
5	0
.	0
7	0
)	0
%	0
,	0
both	0
p	0
<	0
0	0
.	0
01	0
)	0
,	0
and	0
at	0
30	0
minutes	0
after	0
dobutamine	1
(	0
-	0
32	0
(	0
5	0
.	0
3	0
)	0
%	0
,	0
p	0
<	0
0	0
.	0
01	0
)	0
.	0

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

C0NCLUSI0NS	0
:	0
In	0
patients	0
with	0
coronary	3
artery	4
disease	4
,	0
dobutamine	1
induced	0
ischaemia	3
results	0
in	0
prolonged	0
reversible	0
left	3
ventricular	4
dysfunction	4
,	0
presumed	0
to	0
be	0
myocardial	3
stunning	4
,	0
similar	0
to	0
that	0
seen	0
after	0
exercise	0
.	0

Dobutamine	1
induced	0
ischaemia	3
could	0
therefore	0
be	0
used	0
to	0
study	0
the	0
pathophysiology	0
of	0
this	0
phenomenon	0
further	0
in	0
patients	0
with	0
coronary	3
artery	4
disease	4
.	0

Anorexigens	0
and	0
pulmonary	3
hypertension	4
in	0
the	0
United	0
States	0
:	0
results	0
from	0
the	0
surveillance	0
of	0
North	0
American	0
pulmonary	3
hypertension	4
.	0

BACKGR0UND	0
:	0
The	0
use	0
of	0
appetite	0
suppressants	0
in	0
Europe	0
has	0
been	0
associated	0
with	0
the	0
development	0
of	0
primary	3
pulmonary	4
hypertension	4
(	0
PPH	3
)	0
.	0

Recently	0
,	0
fenfluramine	1
appetite	0
suppressants	0
became	0
widely	0
used	0
in	0
the	0
United	0
States	0
but	0
were	0
withdrawn	0
in	0
September	0
1997	0
because	0
of	0
concerns	0
over	0
adverse	0
effects	0
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
We	0
conducted	0
a	0
prospective	0
surveillance	0
study	0
on	0
patients	0
diagnosed	0
with	0
pulmonary	3
hypertension	4
at	0
12	0
large	0
referral	0
centers	0
in	0
North	0
America	0
.	0

Data	0
collected	0
on	0
patients	0
seen	0
from	0
September	0
1	0
,	0
1996	0
,	0
to	0
December	0
31	0
,	0
1997	0
,	0
included	0
the	0
cause	0
of	0
the	0
pulmonary	3
hypertension	4
and	0
its	0
severity	0
.	0

Patients	0
with	0
no	0
identifiable	0
cause	0
of	0
pulmonary	3
hypertension	4
were	0
classed	0
as	0
PPH	3
.	0

A	0
history	0
of	0
drug	0
exposure	0
also	0
was	0
taken	0
with	0
special	0
attention	0
on	0
the	0
use	0
of	0
antidepressants	0
,	0
anorexigens	0
,	0
and	0
amphetamines	1
.	0

RESULTS	0
:	0
Five	0
hundred	0
seventy	0
-	0
nine	0
patients	0
were	0
studied	0
,	0
205	0
with	0
PPH	3
and	0
374	0
with	0
pulmonary	3
hypertension	4
from	0
other	0
causes	0
(	0
secondary	0
pulmonary	3
hypertension	4
[	0
SPH	0
]	0
)	0
.	0

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

However	0
,	0
of	0
the	0
medications	0
surveyed	0
,	0
only	0
the	0
fenfluramines	1
had	0
a	0
significant	0
preferential	0
association	0
with	0
PPH	3
as	0
compared	0
with	0
SPH	0
(	0
adjusted	0
odds	0
ratio	0
for	0
use	0
>	0
6	0
months	0
,	0
7	0
.	0
5	0
;	0
95	0
%	0
confidence	0
interval	0
,	0
1	0
.	0
7	0
to	0
32	0
.	0
4	0
)	0
.	0

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

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

C0NCLUSI0N	0
:	0
The	0
magnitude	0
of	0
the	0
association	0
with	0
PPH	3
,	0
the	0
increase	0
of	0
association	0
with	0
increasing	0
duration	0
of	0
use	0
,	0
and	0
the	0
specificity	0
for	0
fenfluramines	1
are	0
consistent	0
with	0
previous	0
studies	0
indicating	0
that	0
fenfluramines	1
are	0
causally	0
related	0
to	0
PPH	3
.	0

The	0
high	0
prevalence	0
of	0
anorexigen	0
use	0
in	0
patients	0
with	0
SPH	0
also	0
raises	0
the	0
possibility	0
that	0
these	0
drugs	0
precipitate	0
pulmonary	3
hypertension	4
in	0
patients	0
with	0
underlying	0
conditions	0
associated	0
with	0
SPH	0
.	0

Clinical	0
aspects	0
of	0
heparin	1
-	0
induced	0
thrombocytopenia	3
and	0
thrombosis	3
and	0
other	0
side	0
effects	0
of	0
heparin	1
therapy	0
.	0

Heparin	1
,	0
first	0
used	0
to	0
prevent	0
the	0
clotting	0
of	0
blood	0
in	0
vitro	0
,	0
has	0
been	0
clinically	0
used	0
to	0
treat	0
thrombosis	3
for	0
more	0
than	0
50	0
years	0
.	0

Although	0
several	0
new	0
anticoagulant	0
drugs	0
are	0
in	0
development	0
,	0
heparin	1
remains	0
the	0
anticoagulant	0
of	0
choice	0
to	0
treat	0
acute	0
thrombotic	3
episodes	0
.	0

The	0
clinical	0
effects	0
of	0
heparin	1
are	0
meritorious	0
,	0
but	0
side	0
effects	0
do	0
exist	0
.	0

Bleeding	3
is	0
the	0
primary	0
untoward	0
effect	0
of	0
heparin	1
.	0

Major	0
bleeding	3
is	0
of	0
primary	0
concern	0
in	0
patients	0
receiving	0
heparin	1
therapy	0
.	0

However	0
,	0
additional	0
important	0
untoward	0
effects	0
of	0
heparin	1
therapy	0
include	0
heparin	1
-	0
induced	0
thrombocytopenia	3
,	0
heparin	1
-	0
associated	0
osteoporosis	3
,	0
eosinophilia	3
,	0
skin	3
reactions	4
,	0
allergic	3
reactions	4
other	0
than	0
thrombocytopenia	3
,	0
alopecia	3
,	0
transaminasemia	0
,	0
hyperkalemia	3
,	0
hypoaldosteronism	3
,	0
and	0
priapism	3
.	0

These	0
side	0
effects	0
are	0
relatively	0
rare	0
in	0
a	0
given	0
individual	0
,	0
but	0
given	0
the	0
extremely	0
widespread	0
use	0
of	0
heparin	1
,	0
some	0
are	0
quite	0
common	0
,	0
particularly	0
HITT	3
and	0
osteoporosis	3
.	0

Although	0
reasonable	0
incidences	0
of	0
many	0
of	0
these	0
side	0
effects	0
can	0
be	0
"	0
softly	0
"	0
deduced	0
from	0
current	0
reports	0
dealing	0
with	0
unfractionated	0
heparin	1
,	0
at	0
present	0
the	0
incidences	0
of	0
these	0
side	0
effects	0
with	0
newer	0
low	0
molecular	0
weight	0
heparins	1
appear	0
to	0
be	0
much	0
less	0
common	0
.	0

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

A	0
case	0
of	0
bilateral	0
optic	3
neuropathy	4
in	0
a	0
patient	0
on	0
tacrolimus	1
(	0
FK506	1
)	0
therapy	0
after	0
liver	0
transplantation	0
.	0

PURP0SE	0
:	0
To	0
report	0
a	0
case	0
of	0
bilateral	0
optic	3
neuropathy	4
in	0
a	0
patient	0
receiving	0
tacrolimus	1
(	0
FK	1
506	2
,	0
Prograf	0
;	0
Fujisawa	0
USA	0
,	0
Inc	0
,	0
Deerfield	0
,	0
Illinois	0
)	0
for	0
immunosuppression	0
after	0
orthotropic	0
liver	0
transplantation	0
.	0

METH0D	0
:	0
Case	0
report	0
.	0

In	0
a	0
58	0
-	0
year	0
-	0
old	0
man	0
receiving	0
tacrolimus	1
after	0
orthotropic	0
liver	0
transplantation	0
,	0
serial	0
neuro	0
-	0
ophthalmologic	0
examinations	0
and	0
laboratory	0
studies	0
were	0
performed	0
.	0

RESULTS	0
:	0
The	0
patient	0
had	0
episodic	0
deterioration	0
of	0
vision	0
in	0
both	0
eyes	0
,	0
with	0
clinical	0
features	0
resembling	0
ischemic	3
optic	4
neuropathies	4
.	0

Deterioration	3
of	4
vision	4
occurred	0
despite	0
discontinuation	0
of	0
the	0
tacrolimus	1
.	0

C0NCLUSI0N	0
:	0
Tacrolimus	1
and	0
other	0
immunosuppressive	0
agents	0
may	0
be	0
associated	0
with	0
optic	3
nerve	4
toxicity	4
.	0

Hypercalcemia	3
,	0
arrhythmia	3
,	0
and	0
mood	0
stabilizers	0
.	0

Recent	0
findings	0
in	0
a	0
bipolar	3
patient	0
receiving	0
maintenance	0
lithium	1
therapy	0
who	0
developed	0
hypercalcemia	3
and	0
severe	0
bradyarrhythmia	3
prompted	0
the	0
authors	0
to	0
conduct	0
a	0
retrospective	0
study	0
of	0
bipolar	3
patients	0
with	0
lithium	1
-	0
associated	0
hypercalcemia	3
.	0

A	0
printout	0
of	0
all	0
cases	0
of	0
hypercalcemia	3
that	0
presented	0
during	0
a	0
1	0
-	0
year	0
period	0
was	0
generated	0
.	0

After	0
eliminating	0
spurious	0
hypercalcemias	3
or	0
those	0
associated	0
with	0
intravenous	0
fluids	0
,	0
the	0
authors	0
identified	0
18	0
non	0
-	0
lithium	1
-	0
treated	0
patients	0
with	0
hypercalcemias	3
related	0
to	0
malignancies	3
and	0
other	0
medical	0
conditions	0
(	0
group	0
A	0
)	0
and	0
12	0
patients	0
with	0
lithium	1
-	0
associated	0
hypercalcemia	3
(	0
group	0
B	0
)	0
.	0

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

Thus	0
,	0
two	0
control	0
groups	0
were	0
generated	0
:	0
group	0
C1	0
,	0
which	0
included	0
age	0
-	0
and	0
sex	0
-	0
comparable	0
lithium	1
-	0
treated	0
bipolar	3
normocalcemic	0
patients	0
,	0
and	0
group	0
C2	0
,	0
which	0
included	0
bipolar	3
normocalcemic	0
patients	0
treated	0
with	0
anticonvulsant	0
mood	0
stabilizers	0
.	0

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

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

Patients	0
with	0
hypercalcemia	3
resulting	0
from	0
medical	0
diseases	0
and	0
bipolar	3
patients	0
with	0
lithium	1
-	0
associated	0
hypercalcemia	3
had	0
significantly	0
higher	0
frequencies	0
of	0
conduction	0
defects	0
.	0

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

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

Attenuation	0
of	0
nephrotoxicity	3
by	0
a	0
novel	0
lipid	0
nanosphere	0
(	0
NS	0
-	0
718	0
)	0
incorporating	0
amphotericin	1
B	2
.	0

NS	0
-	0
718	0
,	0
a	0
lipid	0
nanosphere	0
incorporating	0
amphotericin	1
B	2
,	0
is	0
effective	0
against	0
pathogenic	0
fungi	0
and	0
has	0
low	0
toxicity	3
.	0

We	0
compared	0
the	0
toxicity	3
of	0
NS	0
-	0
718	0
with	0
that	0
of	0
Fungizone	1
(	0
amphotericin	1
B	2
-	2
sodium	2
deoxycholate	2
;	0
D	1
-	2
AmB	2
)	0
in	0
vitro	0
using	0
renal	0
cell	0
cultures	0
and	0
in	0
vivo	0
by	0
biochemical	0
analysis	0
,	0
histopathological	0
study	0
of	0
the	0
kidney	0
and	0
pharmacokinetic	0
study	0
of	0
amphotericin	1
B	2
following	0
intravenous	0
infusion	0
of	0
the	0
formulation	0
in	0
rats	0
.	0

Incubation	0
with	0
NS	0
-	0
718	0
resulted	0
in	0
significantly	0
less	0
damage	0
of	0
cultured	0
human	0
renal	0
proximal	0
tubular	0
epithelial	0
cells	0
compared	0
with	0
D	1
-	2
AmB	2
.	0

Serum	0
blood	0
urea	1
and	0
creatinine	1
concentrations	0
increased	0
significantly	0
in	0
rats	0
given	0
an	0
iv	0
infusion	0
of	0
D	1
-	2
AmB	2
3	0
mg	0
/	0
kg	0
but	0
not	0
in	0
those	0
given	0
the	0
same	0
dose	0
of	0
NS	0
-	0
718	0
.	0

Histopathological	0
examination	0
of	0
the	0
kidney	0
showed	0
tubular	3
necrosis	4
in	0
D	1
-	2
AmB	2
-	0
treated	0
rats	0
but	0
no	0
change	0
in	0
NS	0
-	0
718	0
-	0
treated	0
rats	0
.	0

Amphotericin	1
B	2
concentrations	0
in	0
the	0
kidney	0
in	0
NS	0
-	0
718	0
-	0
treated	0
rats	0
were	0
higher	0
than	0
those	0
in	0
D	1
-	2
AmB	2
-	0
treated	0
rats	0
.	0

0ur	0
in	0
vitro	0
and	0
in	0
vivo	0
results	0
suggest	0
that	0
incorporation	0
of	0
amphotericin	1
B	2
into	0
lipid	0
nanospheres	0
of	0
NS	0
-	0
718	0
attenuates	0
the	0
nephrotoxicity	3
of	0
amphotericin	1
B	2
.	0

Patterns	0
of	0
sulfadiazine	1
acute	3
nephrotoxicity	4
.	0

Sulfadiazine	1
acute	3
nephrotoxicity	4
is	0
reviving	0
specially	0
because	0
of	0
its	0
use	0
in	0
toxoplasmosis	3
in	0
HIV	0
-	0
positive	0
patients	0
.	0

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

Under	0
treatment	0
with	0
sulfadiazine	1
they	0
developed	0
oliguria	3
,	0
abdominal	3
pain	4
,	0
renal	3
failure	4
and	0
showed	0
multiple	0
radiolucent	0
renal	3
calculi	4
in	0
echography	0
.	0

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

A	0
nephrostomy	0
tube	0
had	0
to	0
be	0
placed	0
in	0
one	0
of	0
the	0
patients	0
for	0
ureteral	3
lithiasis	4
in	0
a	0
single	0
functional	0
kidney	0
.	0

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

Treatment	0
with	0
sulfadiazine	1
requires	0
exquisite	0
control	0
of	0
renal	0
function	0
,	0
an	0
increase	0
in	0
water	0
ingestion	0
and	0
possibly	0
the	0
alcalinization	0
of	0
the	0
urine	0
.	0

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

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

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

Downbeat	3
nystagmus	4
associated	0
with	0
intravenous	0
patient	0
-	0
controlled	0
administration	0
of	0
morphine	1
.	0

IMPLICATI0NS	0
:	0
This	0
case	0
documents	0
a	0
patient	0
who	0
developed	0
dizziness	3
with	0
downbeating	3
nystagmus	4
while	0
receiving	0
a	0
relatively	0
large	0
dose	0
of	0
IV	0
patient	0
-	0
controlled	0
analgesia	0
morphine	1
.	0

Although	0
there	0
have	0
been	0
case	0
reports	0
of	0
epidural	0
morphine	1
with	0
these	0
symptoms	0
and	0
signs	0
,	0
this	0
has	0
not	0
been	0
previously	0
documented	0
with	0
IV	0
or	0
patient	0
-	0
controlled	0
analgesia	0
morphine	1
.	0

Hemodynamic	0
and	0
antiadrenergic	0
effects	0
of	0
dronedarone	1
and	0
amiodarone	1
in	0
animals	0
with	0
a	0
healed	0
myocardial	3
infarction	4
.	0

The	0
hemodynamic	0
and	0
antiadrenergic	0
effects	0
of	0
dronedarone	1
,	0
a	0
noniodinated	0
compound	0
structurally	0
related	0
to	0
amiodarone	1
,	0
were	0
compared	0
with	0
those	0
of	0
amiodarone	1
after	0
prolonged	0
oral	0
administration	0
,	0
both	0
at	0
rest	0
and	0
during	0
sympathetic	0
stimulation	0
in	0
conscious	0
dogs	0
with	0
a	0
healed	0
myocardial	3
infarction	4
.	0

All	0
dogs	0
(	0
n	0
=	0
6	0
)	0
randomly	0
received	0
orally	0
dronedarone	1
(	0
10	0
and	0
30	0
mg	0
/	0
kg	0
)	0
,	0
amiodarone	1
(	0
10	0
and	0
30	0
mg	0
/	0
kg	0
)	0
,	0
and	0
placebo	0
twice	0
daily	0
for	0
7	0
days	0
,	0
with	0
a	0
3	0
-	0
week	0
washout	0
between	0
consecutive	0
treatments	0
.	0

Heart	0
rate	0
(	0
HR	0
)	0
,	0
mean	0
arterial	0
pressure	0
(	0
MBP	0
)	0
,	0
positive	0
rate	0
of	0
increase	0
of	0
left	0
ventricular	0
pressure	0
(	0
+	0
LVdP	0
/	0
dt	0
)	0
,	0
echocardiographically	0
assessed	0
left	0
ventricular	0
ejection	0
fraction	0
(	0
LVEF	0
)	0
,	0
and	0
fractional	0
shortening	0
(	0
FS	0
)	0
,	0
as	0
well	0
as	0
chronotropic	0
response	0
to	0
isoproterenol	1
and	0
exercise	0
-	0
induced	0
sympathetic	0
stimulation	0
were	0
evaluated	0
under	0
baseline	0
and	0
posttreatment	0
conditions	0
.	0

Resting	0
values	0
of	0
LVEF	0
,	0
FS	0
,	0
+	0
LVdP	0
/	0
dt	0
,	0
and	0
MBP	0
remained	0
unchanged	0
whatever	0
the	0
drug	0
and	0
the	0
dosing	0
regimen	0
,	0
whereas	0
resting	0
HR	0
was	0
significantly	0
and	0
dose	0
-	0
dependently	0
lowered	0
after	0
dronedarone	1
and	0
to	0
a	0
lesser	0
extent	0
after	0
amiodarone	1
.	0

Both	0
dronedarone	1
and	0
amiodarone	1
significantly	0
reduced	0
the	0
exercise	0
-	0
induced	0
tachycardia	3
and	0
,	0
at	0
the	0
highest	0
dose	0
,	0
decreased	0
the	0
isoproterenol	1
-	0
induced	0
tachycardia	3
.	0

Thus	0
,	0
dronedarone	1
and	0
amiodarone	1
displayed	0
a	0
similar	0
level	0
of	0
antiadrenergic	0
effect	0
and	0
did	0
not	0
impair	0
the	0
resting	0
left	0
ventricular	0
function	0
.	0

Consequently	0
,	0
dronedarone	1
might	0
be	0
particularly	0
suitable	0
for	0
the	0
treatment	0
and	0
prevention	0
of	0
various	0
clinical	0
arrhythmias	3
,	0
without	0
compromising	0
the	0
left	0
ventricular	0
function	0
.	0

Phase	0
2	0
trial	0
of	0
liposomal	0
doxorubicin	1
(	0
40	0
mg	0
/	0
m	0
(	0
2	0
)	0
)	0
in	0
platinum	1
/	0
paclitaxel	1
-	0
refractory	0
ovarian	3
and	4
fallopian	4
tube	4
cancers	4
and	0
primary	0
carcinoma	3
of	4
the	4
peritoneum	4
.	0

BACKGR0UND	0
:	0
Several	0
studies	0
have	0
demonstrated	0
liposomal	0
doxorubicin	1
(	0
Doxil	1
)	0
to	0
be	0
an	0
active	0
antineoplastic	0
agent	0
in	0
platinum	1
-	0
resistant	0
ovarian	3
cancer	4
,	0
with	0
dose	0
limiting	0
toxicity	3
of	0
the	0
standard	0
dosing	0
regimen	0
(	0
50	0
mg	0
/	0
m	0
(	0
2	0
)	0
q	0
4	0
weeks	0
)	0
being	0
severe	0
erythrodysesthesia	3
(	0
"	0
hand	3
-	4
foot	4
syndrome	4
"	0
)	0
and	0
stomatitis	3
.	0

We	0
wished	0
to	0
develop	0
a	0
more	0
tolerable	0
liposomal	0
doxorubicin	1
treatment	0
regimen	0
and	0
document	0
its	0
level	0
of	0
activity	0
in	0
a	0
well	0
-	0
defined	0
patient	0
population	0
with	0
platinum	1
/	0
paclitaxel	1
-	0
refractory	0
disease	0
.	0

METH0DS	0
AND	0
MATERIALS	0
:	0
Patients	0
with	0
ovarian	3
or	4
fallopian	4
tube	4
cancers	4
or	0
primary	0
peritoneal	3
carcinoma	4
with	0
platinum	1
/	0
paclitaxel	1
-	0
refractory	0
disease	0
(	0
stable	0
or	0
progressive	0
disease	0
following	0
treatment	0
with	0
these	0
agents	0
or	0
previous	0
objective	0
response	0
<	0
3	0
months	0
in	0
duration	0
)	0
were	0
treated	0
with	0
liposomal	0
doxorubicin	1
at	0
a	0
dose	0
of	0
40	0
mg	0
/	0
m	0
(	0
2	0
)	0
q	0
4	0
weeks	0
.	0

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

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

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

0ne	0
patient	0
developed	0
grade	0
3	0
diarrhea	3
requiring	0
hospitalization	0
for	0
hydration	0
.	0

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

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

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

C0NCLUSI0N	0
:	0
This	0
modified	0
liposomal	0
doxorubicin	1
regimen	0
results	0
in	0
less	0
toxicity	3
(	0
stomatitis	3
,	0
hand	3
-	4
foot	4
syndrome	4
)	0
than	0
the	0
standard	0
FDA	0
-	0
approved	0
dose	0
schedule	0
.	0

Definite	0
,	0
although	0
limited	0
,	0
antineoplastic	0
activity	0
is	0
observed	0
in	0
patients	0
with	0
well	0
-	0
defined	0
platinum	1
-	0
and	0
paclitaxel	1
-	0
refractory	0
ovarian	3
cancer	4
.	0

Efficacy	0
of	0
olanzapine	1
in	0
acute	0
bipolar	3
mania	4
:	0
a	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
study	0
.	0

The	0
0lanzipine	1
HGGW	0
Study	0
Group	0
.	0

BACKGR0UND	0
:	0
We	0
compared	0
the	0
efficacy	0
and	0
safety	0
of	0
olanzapine	1
vs	0
placebo	0
for	0
the	0
treatment	0
of	0
acute	0
bipolar	3
mania	4
.	0

METH0DS	0
:	0
Four	0
-	0
week	0
,	0
randomized	0
,	0
double	0
-	0
blind	0
,	0
parallel	0
study	0
.	0

A	0
total	0
of	0
115	0
patients	0
with	0
a	0
DSM	0
-	0
IV	0
diagnosis	0
of	0
bipolar	3
disorder	4
,	0
manic	3
or	0
mixed	0
,	0
were	0
randomized	0
to	0
olanzapine	1
,	0
5	0
to	0
20	0
mg	0
/	0
d	0
(	0
n	0
=	0
55	0
)	0
,	0
or	0
placebo	0
(	0
n	0
=	0
60	0
)	0
.	0

The	0
primary	0
efficacy	0
measure	0
was	0
the	0
Young	0
-	0
Mania	3
Rating	0
Scale	0
(	0
Y	0
-	0
MRS	0
)	0
total	0
score	0
.	0

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

Safety	0
was	0
assessed	0
using	0
adverse	0
events	0
,	0
Extrapyramidal	3
Symptom	4
(	0
EPS	3
)	0
rating	0
scales	0
,	0
laboratory	0
values	0
,	0
electrocardiograms	0
,	0
vital	0
signs	0
,	0
and	0
weight	0
change	0
.	0

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

0lanzapine	1
-	0
treated	0
patients	0
demonstrated	0
a	0
higher	0
rate	0
of	0
response	0
(	0
65	0
%	0
vs	0
43	0
%	0
,	0
respectively	0
;	0
P	0
=	0
.	0
02	0
)	0
and	0
euthymia	0
(	0
61	0
%	0
vs	0
36	0
%	0
,	0
respectively	0
;	0
P	0
=	0
.	0
01	0
)	0
than	0
placebo	0
-	0
treated	0
patients	0
.	0

There	0
were	0
no	0
statistically	0
significant	0
differences	0
in	0
EPSs	3
between	0
groups	0
.	0

However	0
,	0
olanzapine	1
-	0
treated	0
patients	0
had	0
a	0
statistically	0
significant	0
greater	0
mean	0
(	0
+	0
/	0
-	0
SD	0
)	0
weight	3
gain	4
than	0
placebo	0
-	0
treated	0
patients	0
(	0
2	0
.	0
1	0
+	0
/	0
-	0
2	0
.	0
8	0
vs	0
0	0
.	0
45	0
+	0
/	0
-	0
2	0
.	0
3	0
kg	0
,	0
respectively	0
)	0
and	0
also	0
experienced	0
more	0
treatment	0
-	0
emergent	0
somnolence	3
(	0
21	0
patients	0
[	0
38	0
.	0
2	0
%	0
]	0
vs	0
5	0
[	0
8	0
.	0
3	0
%	0
]	0
,	0
respectively	0
)	0
.	0

C0NCLUSI0N	0
:	0
0lanzapine	1
demonstrated	0
greater	0
efficacy	0
than	0
placebo	0
in	0
the	0
treatment	0
of	0
acute	0
bipolar	3
mania	4
and	0
was	0
generally	0
well	0
tolerated	0
.	0

The	0
effect	0
of	0
pupil	3
dilation	4
with	0
tropicamide	1
on	0
vision	0
and	0
driving	0
simulator	0
performance	0
.	0

PURP0SE	0
:	0
To	0
assess	0
the	0
effect	0
of	0
pupil	3
dilation	4
on	0
vision	0
and	0
driving	0
ability	0
.	0

METH0DS	0
:	0
A	0
series	0
of	0
tests	0
on	0
various	0
parameters	0
of	0
visual	0
function	0
and	0
driving	0
simulator	0
performance	0
were	0
performed	0
on	0
12	0
healthy	0
drivers	0
,	0
before	0
and	0
after	0
pupil	3
dilation	4
using	0
guttae	0
tropicamide	1
1	0
%	0
.	0

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

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

Useful	0
Field	0
of	0
View	0
(	0
UF0V	0
-	0
-	0
a	0
test	0
of	0
visual	0
attention	0
)	0
was	0
also	0
undertaken	0
.	0

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

RESULTS	0
:	0
Pupillary	3
dilation	4
resulted	0
in	0
a	0
statistically	0
significant	0
deterioration	0
in	0
CT	0
and	0
HCVA	0
only	0
.	0

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

Little	0
evidence	0
emerged	0
for	0
deterioration	0
in	0
FIELDS	0
and	0
UF0V	0
.	0

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

C0NCLUSI0NS	0
:	0
Pupillary	3
dilation	4
may	0
lead	0
to	0
a	0
decrease	0
in	0
vision	0
and	0
daylight	0
driving	0
performance	0
in	0
young	0
people	0
.	0

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

A	0
case	0
of	0
isotretinoin	3
embryopathy	4
with	0
bilateral	0
anotia	3
and	0
Taussig	3
-	4
Bing	4
malformation	4
.	0

We	0
report	0
a	0
newborn	0
infant	0
with	0
multiple	0
congenital	0
anomalies	0
(	0
anotia	3
and	0
Taussig	3
-	4
Bing	4
malformation	4
)	0
due	0
to	0
exposure	0
to	0
isotretinoin	1
within	0
the	0
first	0
trimester	0
.	0

In	0
this	0
paper	0
we	0
aim	0
to	0
draw	0
to	0
the	0
fact	0
that	0
caution	0
is	0
needed	0
when	0
prescribing	0
vitamin	1
A	2
-	0
containing	0
drugs	0
to	0
women	0
of	0
childbearing	0
years	0
.	0

Effect	0
of	0
methoxamine	1
on	0
maximum	0
urethral	0
pressure	0
in	0
women	0
with	0
genuine	0
stress	3
incontinence	4
:	0
a	0
placebo	0
-	0
controlled	0
,	0
double	0
-	0
blind	0
crossover	0
study	0
.	0

The	0
aim	0
of	0
the	0
study	0
was	0
to	0
evaluate	0
the	0
potential	0
role	0
for	0
a	0
selective	0
alpha1	0
-	0
adrenoceptor	0
agonist	0
in	0
the	0
treatment	0
of	0
urinary	3
stress	4
incontinence	4
.	0

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

Half	0
log	0
incremental	0
doses	0
of	0
intravenous	0
methoxamine	1
or	0
placebo	0
(	0
saline	0
)	0
were	0
administered	0
to	0
a	0
group	0
of	0
women	0
with	0
genuine	0
stress	3
incontinence	4
while	0
measuring	0
maximum	0
urethral	0
pressure	0
(	0
MUP	0
)	0
,	0
blood	0
pressure	0
,	0
heart	0
rate	0
,	0
and	0
symptomatic	0
side	0
effects	0
.	0

Methoxamine	1
evoked	0
non	0
-	0
significant	0
increases	0
in	0
MUP	0
and	0
diastolic	0
blood	0
pressure	0
but	0
caused	0
a	3
significant	4
rise	4
in	4
systolic	4
blood	4
pressure	4
and	0
significant	0
fall	0
in	0
heart	0
rate	0
at	0
maximum	0
dosage	0
.	0

Systemic	0
side	0
effects	0
including	0
piloerection	0
,	0
headache	3
,	0
and	0
cold	0
extremities	0
were	0
experienced	0
in	0
all	0
subjects	0
.	0

The	0
results	0
indicate	0
that	0
the	0
clinical	0
usefulness	0
of	0
direct	0
,	0
peripherally	0
acting	0
sub	0
-	0
type	0
-	0
selective	0
alpha1	0
-	0
adrenoceptor	0
agonists	0
in	0
the	0
medical	0
treatment	0
of	0
stress	3
incontinence	4
may	0
be	0
limited	0
by	0
associated	0
piloerection	0
and	0
cardiovascular	0
side	0
effects	0
.	0

Hyperglycemic	3
effect	0
of	0
amino	1
compounds	0
structurally	0
related	0
to	0
caproate	1
in	0
rats	0
.	0

The	0
chronic	0
feeding	0
of	0
small	0
amounts	0
(	0
0	0
.	0
3	0
-	0
3	0
%	0
of	0
diet	0
weight	0
)	0
of	0
certain	0
amino	1
derivatives	0
of	0
caproate	1
resulted	0
in	0
hyperglycemia	3
,	0
an	0
elevated	0
glucose	1
tolerance	0
curve	0
and	0
,	0
occasionally	0
,	0
glucosuria	3
.	0

Effective	0
compounds	0
included	0
norleucine	1
,	0
norvaline	1
,	0
glutamate	1
,	0
epsilon	1
-	2
aminocaproate	2
,	0
methionine	1
,	0
and	0
leucine	1
.	0

Toleration	0
of	0
high	0
doses	0
of	0
angiotensin	1
-	2
converting	2
enzyme	2
inhibitors	2
in	0
patients	0
with	0
chronic	0
heart	3
failure	4
:	0
results	0
from	0
the	0
ATLAS	0
trial	0
.	0

The	0
Assessment	0
of	0
Treatment	0
with	0
Lisinopril	1
and	0
Survival	0
.	0

BACKGR0UND	0
:	0
Treatment	0
with	0
angiotensin	1
-	2
converting	2
enzyme	2
(	2
ACE	2
)	2
inhibitors	2
reduces	0
mortality	0
and	0
morbidity	0
in	0
patients	0
with	0
chronic	0
heart	3
failure	4
(	0
CHF	3
)	0
,	0
but	0
most	0
affected	0
patients	0
are	0
not	0
receiving	0
these	0
agents	0
or	0
are	0
being	0
treated	0
with	0
doses	0
lower	0
than	0
those	0
found	0
to	0
be	0
efficacious	0
in	0
trials	0
,	0
primarily	0
because	0
of	0
concerns	0
about	0
the	0
safety	0
and	0
tolerability	0
of	0
these	0
agents	0
,	0
especially	0
at	0
the	0
recommended	0
doses	0
.	0

The	0
present	0
study	0
examines	0
the	0
safety	0
and	0
tolerability	0
of	0
high	0
-	0
compared	0
with	0
low	0
-	0
dose	0
lisinopril	1
in	0
CHF	3
.	0

METH0DS	0
:	0
The	0
Assessment	0
of	0
Lisinopril	1
and	0
Survival	0
study	0
was	0
a	0
multicenter	0
,	0
randomized	0
,	0
double	0
-	0
blind	0
trial	0
in	0
which	0
patients	0
with	0
or	0
without	0
previous	0
ACE	1
inhibitor	2
treatment	0
were	0
stabilized	0
receiving	0
medium	0
-	0
dose	0
lisinopril	1
(	0
12	0
.	0
5	0
or	0
15	0
.	0
0	0
mg	0
once	0
daily	0
[	0
0D	0
]	0
)	0
for	0
2	0
to	0
4	0
weeks	0
and	0
then	0
randomized	0
to	0
high	0
-	0
(	0
35	0
.	0
0	0
or	0
32	0
.	0
5	0
mg	0
0D	0
)	0
or	0
low	0
-	0
dose	0
(	0
5	0
.	0
0	0
or	0
2	0
.	0
5	0
mg	0
0D	0
)	0
groups	0
.	0

Patients	0
with	0
New	0
York	0
Heart	0
Association	0
classes	0
II	0
to	0
IV	0
CHF	3
and	0
left	0
ventricular	0
ejection	0
fractions	0
of	0
no	0
greater	0
than	0
0	0
.	0
30	0
(	0
n	0
=	0
3164	0
)	0
were	0
randomized	0
and	0
followed	0
up	0
for	0
a	0
median	0
of	0
46	0
months	0
.	0

We	0
examined	0
the	0
occurrence	0
of	0
adverse	0
events	0
and	0
the	0
need	0
for	0
discontinuation	0
and	0
dose	0
reduction	0
during	0
treatment	0
,	0
with	0
a	0
focus	0
on	0
hypotension	3
and	0
renal	3
dysfunction	4
.	0

RESULTS	0
:	0
0f	0
405	0
patients	0
not	0
previously	0
receiving	0
an	0
ACE	1
inhibitor	2
,	0
doses	0
in	0
only	0
4	0
.	0
2	0
%	0
could	0
not	0
be	0
titrated	0
to	0
the	0
medium	0
doses	0
required	0
for	0
randomization	0
because	0
of	0
symptoms	0
possibly	0
related	0
to	0
hypotension	3
(	0
2	0
.	0
0	0
%	0
)	0
or	0
because	0
of	0
renal	3
dysfunction	4
or	0
hyperkalemia	3
(	0
2	0
.	0
3	0
%	0
)	0
.	0

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

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

Subgroups	0
presumed	0
to	0
be	0
at	0
higher	0
risk	0
for	0
ACE	1
inhibitor	2
intolerance	0
(	0
blood	0
pressure	0
,	0
<	0
120	0
mm	0
Hg	0
;	0
creatinine	1
,	0
>	0
or	0
=	0
132	0
.	0
6	0
micromol	0
/	0
L	0
[	0
>	0
or	0
=	0
1	0
.	0
5	0
mg	0
/	0
dL	0
]	0
;	0
age	0
,	0
>	0
or	0
=	0
70	0
years	0
;	0
and	0
patients	0
with	0
diabetes	3
)	0
generally	0
tolerated	0
the	0
high	0
-	0
dose	0
strategy	0
.	0

C0NCLUSI0NS	0
:	0
These	0
findings	0
demonstrate	0
that	0
ACE	1
inhibitor	2
therapy	0
in	0
most	0
patients	0
with	0
CHF	3
can	0
be	0
successfully	0
titrated	0
to	0
and	0
maintained	0
at	0
high	0
doses	0
,	0
and	0
that	0
more	0
aggressive	0
use	0
of	0
these	0
agents	0
is	0
warranted	0
.	0

Cocaine	1
,	0
ethanol	1
,	0
and	0
cocaethylene	1
cardiotoxity	3
in	0
an	0
animal	0
model	0
of	0
cocaine	3
and	4
ethanol	4
abuse	4
.	0

0BJECTIVES	0
:	0
Simultaneous	0
abuse	3
of	4
cocaine	4
and	4
ethanol	4
affects	0
12	0
million	0
Americans	0
annually	0
.	0

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

Their	0
combined	0
cardiac	3
toxicity	4
may	0
be	0
due	0
to	0
independent	0
effects	0
of	0
each	0
drug	0
;	0
however	0
,	0
they	0
may	0
also	0
be	0
due	0
to	0
cocaethylene	1
(	0
CE	1
)	0
,	0
a	0
cocaine	1
metabolite	0
formed	0
only	0
in	0
the	0
presence	0
of	0
ethanol	1
.	0

The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
delineate	0
the	0
role	0
of	0
CE	1
in	0
the	0
combined	0
cardiotoxicity	3
of	0
cocaine	1
and	0
ethanol	1
in	0
a	0
model	0
simulating	0
their	0
abuse	0
.	0

METH0DS	0
:	0
Twenty	0
-	0
three	0
dogs	0
were	0
randomized	0
to	0
receive	0
either	0
1	0
)	0
three	0
intravenous	0
(	0
IV	0
)	0
boluses	0
of	0
cocaine	1
7	0
.	0
5	0
mg	0
/	0
kg	0
with	0
ethanol	1
(	0
1	0
g	0
/	0
kg	0
)	0
as	0
an	0
IV	0
infusion	0
(	0
C	0
+	0
E	0
,	0
n	0
=	0
8	0
)	0
,	0
2	0
)	0
three	0
cocaine	1
boluses	0
only	0
(	0
C	0
,	0
n	0
=	0
6	0
)	0
,	0
3	0
)	0
ethanol	1
infusion	0
only	0
(	0
E	0
,	0
n	0
=	0
5	0
)	0
,	0
or	0
4	0
)	0
placebo	0
boluses	0
and	0
infusion	0
(	0
n	0
=	0
4	0
)	0
.	0

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

RESULTS	0
:	0
Two	0
of	0
eight	0
dogs	0
in	0
the	0
C	0
+	0
E	0
group	0
experienced	0
cardiovascular	3
collapse	4
.	0

The	0
most	0
dramatic	0
hemodynamic	0
changes	0
occurred	0
after	0
each	0
cocaine	1
bolus	0
in	0
the	0
C	0
+	0
E	0
and	0
C	0
only	0
groups	0
;	0
however	0
,	0
persistent	0
hemodynamic	0
changes	0
occurred	0
in	0
the	0
C	0
+	0
E	0
group	0
.	0

Peak	0
CE	1
levels	0
were	0
associated	0
with	0
a	0
45	0
%	0
(	0
SD	0
+	0
/	0
-	0
22	0
%	0
,	0
95	0
%	0
CI	0
=	0
22	0
%	0
to	0
69	0
%	0
)	0
decrease	3
in	4
cardiac	4
output	4
(	0
p	0
<	0
0	0
.	0
05	0
)	0
,	0
a	0
56	0
%	0
(	0
SD	0
+	0
/	0
-	0
23	0
%	0
,	0
95	0
%	0
CI	0
=	0
32	0
%	0
to	0
80	0
%	0
)	0
decrease	0
in	0
dP	0
/	0
dt	0
(	0
max	0
)	0
(	0
p	0
<	0
.	0
006	0
)	0
,	0
and	0
a	0
23	0
%	0
(	0
SD	0
+	0
/	0
-	0
15	0
%	0
,	0
95	0
%	0
CI	0
=	0
7	0
%	0
to	0
49	0
%	0
)	0
decrease	0
in	0
SV0	0
(	0
2	0
)	0
(	0
p	0
<	0
0	0
.	0
025	0
)	0
.	0

Ventricular	3
arrhythmias	4
were	0
primarily	0
observed	0
in	0
the	0
C	0
+	0
E	0
group	0
,	0
in	0
which	0
four	0
of	0
eight	0
dogs	0
experienced	0
ventricular	3
tachycardia	4
.	0

C0NCLUSI0NS	0
:	0
Cocaine	1
and	0
ethanol	1
in	0
combination	0
were	0
more	0
toxic	0
than	0
either	0
substance	0
alone	0
.	0

Co	0
-	0
administration	0
resulted	0
in	0
prolonged	0
cardiac	3
toxicity	4
and	0
was	0
dysrhythmogenic	0
.	0

Peak	0
serum	0
cocaethylene	1
concentrations	0
were	0
associated	0
with	0
prolonged	0
myocardial	3
depression	4
.	0

Worsening	0
of	0
Parkinsonism	3
after	0
the	0
use	0
of	0
veralipride	1
for	0
treatment	0
of	0
menopause	0
:	0
case	0
report	0
.	0

We	0
describe	0
a	0
female	0
patient	0
with	0
stable	0
Parkinson	3
'	4
s	4
disease	4
who	0
has	0
shown	0
a	0
marked	0
worsening	0
of	0
her	0
motor	0
functions	0
following	0
therapy	0
of	0
menopause	0
related	0
symptoms	0
with	0
veralipride	1
,	0
as	0
well	0
as	0
the	0
improvement	0
of	0
her	0
symptoms	0
back	0
to	0
baseline	0
after	0
discontinuation	0
of	0
the	0
drug	0
.	0

We	0
emphasize	0
the	0
anti	0
-	0
dopaminergic	0
effect	0
of	0
veralipride	1
.	0

Viracept	1
and	0
irregular	3
heartbeat	4
warning	0
.	0

A	0
group	0
of	0
doctors	0
in	0
Boston	0
warn	0
that	0
the	0
protease	0
inhibitor	0
Viracept	1
may	0
cause	0
an	0
irregular	3
heart	4
beat	4
,	0
known	0
as	0
bradycardia	3
,	0
in	0
people	0
with	0
HIV	0
.	0

Bradycardia	3
occurred	0
in	0
a	0
45	0
-	0
year	0
-	0
old	0
male	0
patient	0
who	0
was	0
Viracept	1
in	0
combination	0
with	0
other	0
anti	0
-	0
HIV	0
drugs	0
.	0

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

Frequency	0
of	0
appearance	0
of	0
myeloperoxidase	0
-	0
antineutrophil	0
cytoplasmic	0
antibody	0
(	0
MP0	0
-	0
ANCA	0
)	0
in	0
Graves	3
'	4
disease	4
patients	0
treated	0
with	0
propylthiouracil	1
and	0
the	0
relationship	0
between	0
MP0	0
-	0
ANCA	0
and	0
clinical	0
manifestations	0
.	0

0BJECTIVE	0
:	0
Myeloperoxidase	0
antineutrophil	0
cytoplasmic	0
antibody	0
(	0
MP0	0
-	0
ANCA	0
)	0
-	0
positive	0
vasculitis	3
has	0
been	0
reported	0
in	0
patients	0
with	0
Graves	3
'	4
disease	4
who	0
were	0
treated	0
with	0
propylthiouracil	1
(	0
PTU	1
)	0
.	0

The	0
appearance	0
of	0
MP0	0
-	0
ANCA	0
in	0
these	0
cases	0
was	0
suspected	0
of	0
being	0
related	0
to	0
PTU	1
because	0
the	0
titres	0
of	0
MP0	0
-	0
ANCA	0
decreased	0
when	0
PTU	1
was	0
stopped	0
.	0

Nevertheless	0
,	0
there	0
have	0
been	0
no	0
studies	0
on	0
the	0
temporal	0
relationship	0
between	0
the	0
appearance	0
of	0
MP0	0
-	0
ANCA	0
and	0
vasculitis	3
during	0
PTU	1
therapy	0
,	0
or	0
on	0
the	0
incidence	0
of	0
MP0	0
-	0
ANCA	0
in	0
untreated	0
Graves	3
'	4
disease	4
patients	0
.	0

Therefore	0
,	0
we	0
sought	0
to	0
address	0
these	0
parameters	0
in	0
patients	0
with	0
Graves	3
'	4
disease	4
.	0

PATIENTS	0
:	0
We	0
investigated	0
102	0
untreated	0
patients	0
with	0
hyperthyroidism	3
due	0
to	0
Graves	3
'	4
disease	4
for	0
the	0
presence	0
of	0
MP0	0
-	0
ANCA	0
,	0
and	0
for	0
the	0
development	0
vasculitis	3
after	0
starting	0
PTU	1
therapy	0
.	0

Twenty	0
-	0
nine	0
of	0
them	0
were	0
later	0
excluded	0
because	0
of	0
adverse	0
effects	0
of	0
PTU	1
or	0
because	0
the	0
observation	0
period	0
was	0
less	0
than	0
3	0
months	0
.	0

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

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

MEASUREMENTS	0
:	0
MP0	0
-	0
ANCA	0
was	0
measured	0
at	0
intervals	0
of	0
2	0
-	0
6	0
months	0
.	0

RESULTS	0
:	0
Before	0
treatment	0
,	0
the	0
MP0	0
-	0
ANCA	0
titres	0
of	0
all	0
102	0
untreated	0
Graves	3
'	4
disease	4
patients	0
were	0
within	0
the	0
reference	0
range	0
(	0
below	0
10	0
U	0
/	0
ml	0
)	0
.	0

Three	0
(	0
4	0
.	0
1	0
%	0
)	0
of	0
the	0
73	0
patients	0
were	0
positive	0
for	0
MP0	0
-	0
ANCA	0
at	0
13	0
,	0
16	0
and	0
17	0
months	0
,	0
respectively	0
,	0
after	0
the	0
start	0
of	0
PTU	1
therapy	0
.	0

In	0
two	0
of	0
them	0
,	0
the	0
MP0	0
-	0
ANCA	0
titres	0
transiently	0
increased	0
to	0
12	0
.	0
8	0
and	0
15	0
.	0
0	0
U	0
/	0
ml	0
,	0
respectively	0
,	0
despite	0
continued	0
PTU	1
therapy	0
,	0
but	0
no	0
vasculitic	3
disorders	4
developed	0
.	0

In	0
the	0
third	0
patient	0
,	0
the	0
MP0	0
-	0
ANCA	0
titre	0
increased	0
to	0
204	0
U	0
/	0
ml	0
and	0
she	0
developed	0
a	0
higher	0
fever	3
,	0
oral	3
ulcers	4
and	0
polyarthralgia	3
,	0
but	0
the	0
symptoms	0
resolved	0
2	0
weeks	0
after	0
stopping	0
PTU	1
therapy	0
,	0
and	0
the	0
MP0	0
-	0
ANCA	0
titre	0
decreased	0
to	0
20	0
.	0
7	0
U	0
/	0
ml	0
by	0
4	0
months	0
after	0
discontinuing	0
PTU	1
.	0

C0NCLUSI0NS	0
:	0
PTU	1
therapy	0
may	0
be	0
related	0
to	0
the	0
appearance	0
of	0
MP0	0
-	0
ANCA	0
,	0
but	0
MP0	0
-	0
ANCA	0
does	0
not	0
appear	0
to	0
be	0
closely	0
related	0
to	0
vasculitis	3
.	0

Prevalence	0
of	0
heart	3
disease	4
in	0
asymptomatic	0
chronic	0
cocaine	1
users	0
.	0

To	0
determine	0
the	0
prevalence	0
of	0
heart	3
disease	4
in	0
outpatient	0
young	0
asymptomatic	0
chronic	0
cocaine	1
users	0
,	0
35	0
cocaine	1
users	0
and	0
32	0
age	0
-	0
matched	0
controls	0
underwent	0
resting	0
and	0
exercise	0
electrocardiography	0
(	0
ECG	0
)	0
and	0
Doppler	0
echocardiography	0
.	0

Findings	0
consistent	0
with	0
coronary	3
artery	4
disease	4
were	0
detected	0
in	0
12	0
(	0
34	0
%	0
)	0
patients	0
and	0
3	0
(	0
9	0
%	0
)	0
controls	0
(	0
p	0
=	0
0	0
.	0
01	0
)	0
.	0

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

Finally	0
,	0
resting	0
and	0
peak	0
exercise	0
abnormal	3
left	4
ventricular	4
filling	4
was	0
detected	0
in	0
38	0
and	0
35	0
%	0
of	0
patients	0
as	0
compared	0
to	0
19	0
and	0
9	0
%	0
of	0
controls	0
,	0
respectively	0
(	0
p	0
=	0
0	0
.	0
11	0
and	0
0	0
.	0
02	0
,	0
respectively	0
)	0
.	0

We	0
conclude	0
that	0
coronary	3
artery	4
or	4
myocardial	4
disease	4
is	0
common	0
(	0
38	0
%	0
)	0
in	0
young	0
asymptomatic	0
chronic	0
cocaine	1
users	0
.	0

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

Cardioprotective	0
effects	0
of	0
Picrorrhiza	0
kurroa	0
against	0
isoproterenol	1
-	0
induced	0
myocardial	0
stress	0
in	0
rats	0
.	0

The	0
cardioprotective	0
effect	0
of	0
the	0
ethanol	1
extract	0
of	0
Picrorrhiza	0
kurroa	0
rhizomes	0
and	0
roots	0
(	0
PK	0
)	0
on	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
in	0
rats	0
with	0
respect	0
to	0
lipid	0
metabolism	0
in	0
serum	0
and	0
heart	0
tissue	0
has	0
been	0
investigated	0
.	0

0ral	0
pre	0
-	0
treatment	0
with	0
PK	0
(	0
80	0
mg	0
kg	0
(	0
-	0
1	0
)	0
day	0
(	0
-	0
1	0
)	0
for	0
15	0
days	0
)	0
significantly	0
prevented	0
the	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
and	0
maintained	0
the	0
rats	0
at	0
near	0
normal	0
status	0
.	0

Phase	0
2	0
early	0
afterdepolarization	0
as	0
a	0
trigger	0
of	0
polymorphic	0
ventricular	3
tachycardia	4
in	0
acquired	0
long	3
-	4
QT	4
syndrome	4
:	0
direct	0
evidence	0
from	0
intracellular	0
recordings	0
in	0
the	0
intact	0
left	0
ventricular	0
wall	0
.	0

BACKGR0UND	0
:	0
This	0
study	0
examined	0
the	0
role	0
of	0
phase	0
2	0
early	0
afterdepolarization	0
(	0
EAD	0
)	0
in	0
producing	0
a	0
trigger	0
to	0
initiate	0
torsade	3
de	4
pointes	4
(	0
TdP	3
)	0
with	0
QT	3
prolongation	4
induced	0
by	0
dl	0
-	0
sotalol	1
and	0
azimilide	1
.	0

The	0
contribution	0
of	0
transmural	0
dispersion	0
of	0
repolarization	0
(	0
TDR	0
)	0
to	0
transmural	0
propagation	0
of	0
EAD	0
and	0
the	0
maintenance	0
of	0
TdP	3
was	0
also	0
evaluated	0
.	0

METH0DS	0
AND	0
RESULTS	0
:	0
Transmembrane	0
action	0
potentials	0
from	0
epicardium	0
,	0
midmyocardium	0
,	0
and	0
endocardium	0
were	0
recorded	0
simultaneously	0
,	0
together	0
with	0
a	0
transmural	0
ECG	0
,	0
in	0
arterially	0
perfused	0
canine	0
and	0
rabbit	0
left	0
ventricular	0
preparations	0
.	0

dl	0
-	0
Sotalol	1
preferentially	0
prolonged	0
action	0
potential	0
duration	0
(	0
APD	0
)	0
in	0
M	0
cells	0
dose	0
-	0
dependently	0
(	0
1	0
to	0
100	0
micromol	0
/	0
L	0
)	0
,	0
leading	0
to	0
QT	3
prolongation	4
and	0
an	0
increase	0
in	0
TDR	0
.	0

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

Unlike	0
dl	0
-	0
sotalol	1
,	0
azimilide	1
(	0
>	0
3	0
micromol	0
/	0
L	0
)	0
increased	0
epicardial	0
APD	0
markedly	0
,	0
causing	0
a	0
diminished	0
TDR	0
.	0

Although	0
both	0
dl	0
-	0
sotalol	1
and	0
azimilide	1
rarely	0
induced	0
EADs	0
in	0
canine	0
left	0
ventricles	0
,	0
they	0
produced	0
frequent	0
EADs	0
in	0
rabbits	0
,	0
in	0
which	0
more	0
pronounced	0
QT	3
prolongation	4
was	0
seen	0
.	0

An	0
increase	0
in	0
TDR	0
by	0
dl	0
-	0
sotalol	1
facilitated	0
transmural	0
propagation	0
of	0
EADs	0
that	0
initiated	0
multiple	0
episodes	0
of	0
spontaneous	0
TdP	3
in	0
3	0
of	0
6	0
rabbit	0
left	0
ventricles	0
.	0

0f	0
note	0
,	0
although	0
azimilide	1
(	0
3	0
to	0
10	0
micromol	0
/	0
L	0
)	0
increased	0
APD	0
more	0
than	0
dl	0
-	0
sotalol	1
,	0
its	0
EADs	0
often	0
failed	0
to	0
propagate	0
transmurally	0
,	0
probably	0
because	0
of	0
a	0
diminished	0
TDR	0
.	0

C0NCLUSI0NS	0
:	0
This	0
study	0
provides	0
the	0
first	0
direct	0
evidence	0
from	0
intracellular	0
action	0
potential	0
recordings	0
that	0
phase	0
2	0
EAD	0
can	0
be	0
generated	0
from	0
intact	0
ventricular	0
wall	0
and	0
produce	0
a	0
trigger	0
to	0
initiate	0
the	0
onset	0
of	0
TdP	3
under	0
QT	3
prolongation	4
.	0

A	0
pilot	0
study	0
to	0
assess	0
the	0
safety	0
of	0
dobutamine	1
stress	0
echocardiography	0
in	0
the	0
emergency	0
department	0
evaluation	0
of	0
cocaine	1
-	0
associated	0
chest	3
pain	4
.	0

STUDY	0
0BJECTIVE	0
:	0
Chest	3
pain	4
in	0
the	0
setting	0
of	0
cocaine	1
use	0
poses	0
a	0
diagnostic	0
dilemma	0
.	0

Dobutamine	1
stress	0
echocardiography	0
(	0
DSE	0
)	0
is	0
a	0
widely	0
available	0
and	0
sensitive	0
test	0
for	0
evaluating	0
cardiac	0
ischemia	3
.	0

Because	0
of	0
the	0
theoretical	0
concern	0
regarding	0
administration	0
of	0
dobutamine	1
in	0
the	0
setting	0
of	0
cocaine	1
use	0
,	0
we	0
conducted	0
a	0
pilot	0
study	0
to	0
assess	0
the	0
safety	0
of	0
DSE	0
in	0
emergency	0
department	0
patients	0
with	0
cocaine	1
-	0
associated	0
chest	3
pain	4
.	0

METH0DS	0
:	0
A	0
prospective	0
case	0
series	0
was	0
conducted	0
in	0
the	0
intensive	0
diagnostic	0
and	0
treatment	0
unit	0
in	0
the	0
ED	0
of	0
an	0
urban	0
tertiary	0
-	0
care	0
teaching	0
hospital	0
.	0

Patients	0
were	0
eligible	0
for	0
DSE	0
if	0
they	0
had	0
used	0
cocaine	1
within	0
24	0
hours	0
preceding	0
the	0
onset	0
of	0
chest	3
pain	4
and	0
had	0
a	0
normal	0
ECG	0
and	0
tropinin	0
I	0
level	0
.	0

Patients	0
exhibiting	0
signs	0
of	0
continuing	0
cocaine	1
toxicity	3
were	0
excluded	0
from	0
the	0
study	0
.	0

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

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

Two	0
patients	0
had	0
inadequate	0
resting	0
images	0
,	0
one	0
DSE	0
was	0
terminated	0
because	0
of	0
inferior	0
hypokinesis	3
,	0
another	0
DSE	0
was	0
terminated	0
because	0
of	0
a	0
rate	0
-	0
related	0
atrial	0
conduction	0
deficit	0
,	0
and	0
1	0
patient	0
did	0
not	0
reach	0
the	0
target	0
heart	0
rate	0
.	0

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

None	0
of	0
the	0
patients	0
experienced	0
signs	0
of	0
exaggerated	0
adrenergic	0
response	0
,	0
which	0
was	0
defined	0
as	0
a	0
systolic	0
blood	0
pressure	0
of	0
greater	0
than	0
200	0
mm	0
Hg	0
or	0
the	0
occurrence	0
of	0
tachydysrhythmias	3
(	0
excluding	0
sinus	3
tachycardia	4
)	0
.	0

Further	0
suggesting	0
lack	0
of	0
exaggerated	0
adrenergic	0
response	0
,	0
13	0
(	0
65	0
%	0
)	0
of	0
20	0
patients	0
required	0
supplemental	0
atropine	1
to	0
reach	0
their	0
target	0
heart	0
rates	0
.	0

C0NCLUSI0N	0
:	0
No	0
exaggerated	0
adrenergic	0
response	0
was	0
detected	0
when	0
dobutamine	1
was	0
administered	0
to	0
patients	0
with	0
cocaine	1
-	0
related	0
chest	3
pain	4
.	0

Prenatal	0
cocaine	1
exposure	0
and	0
cranial	0
sonographic	0
findings	0
in	0
preterm	3
infants	4
.	0

PURP0SE	0
:	0
Prenatal	0
cocaine	1
exposure	0
has	0
been	0
linked	0
with	0
subependymal	0
hemorrhage	3
and	0
the	0
formation	0
of	0
cysts	3
that	0
are	0
detectable	0
on	0
cranial	0
sonography	0
in	0
neonates	0
born	0
at	0
term	0
.	0

We	0
sought	0
to	0
determine	0
if	0
prenatal	0
cocaine	1
exposure	0
increases	0
the	0
incidence	0
of	0
subependymal	3
cysts	4
in	0
preterm	3
infants	4
.	0

METH0DS	0
:	0
We	0
retrospectively	0
reviewed	0
the	0
medical	0
records	0
and	0
cranial	0
sonograms	0
obtained	0
during	0
a	0
1	0
-	0
year	0
period	0
on	0
122	0
premature	3
(	4
<	4
36	4
weeks	4
of	4
gestation	4
)	4
infants	4
.	0

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

Infants	0
were	0
assigned	0
to	0
the	0
cocaine	1
-	0
exposed	0
group	0
if	0
there	0
was	0
a	0
maternal	0
history	0
of	0
cocaine	3
abuse	4
during	0
pregnancy	0
or	0
if	0
maternal	0
or	0
neonatal	0
urine	0
toxicology	0
results	0
were	0
positive	0
at	0
the	0
time	0
of	0
delivery	0
.	0

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

The	0
incidence	0
of	0
subependymal	3
cysts	4
in	0
the	0
117	0
remaining	0
infants	0
was	0
14	0
%	0
(	0
16	0
of	0
117	0
)	0
.	0

The	0
incidence	0
of	0
subependymal	3
cysts	4
in	0
infants	0
exposed	0
to	0
cocaine	1
prenatally	0
was	0
44	0
%	0
(	0
8	0
of	0
18	0
)	0
compared	0
with	0
8	0
%	0
(	0
8	0
of	0
99	0
)	0
in	0
the	0
unexposed	0
group	0
(	0
p	0
<	0
0	0
.	0
01	0
)	0
.	0

C0NCLUSI0NS	0
:	0
We	0
found	0
an	0
increased	0
incidence	0
of	0
subependymal	3
cyst	4
formation	0
in	0
preterm	3
infants	4
who	0
were	0
exposed	0
to	0
cocaine	1
prenatally	0
.	0

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

Thalidomide	1
neuropathy	3
in	0
patients	0
treated	0
for	0
metastatic	0
prostate	3
cancer	4
.	0

We	0
prospectively	0
evaluated	0
thalidomide	1
-	0
induced	0
neuropathy	3
using	0
electrodiagnostic	0
studies	0
.	0

Sixty	0
-	0
seven	0
men	0
with	0
metastatic	0
androgen	1
-	0
independent	0
prostate	3
cancer	4
in	0
an	0
open	0
-	0
label	0
trial	0
of	0
oral	0
thalidomide	1
underwent	0
neurologic	0
examinations	0
and	0
nerve	0
conduction	0
studies	0
(	0
NCS	0
)	0
prior	0
to	0
and	0
at	0
3	0
-	0
month	0
intervals	0
during	0
treatment	0
.	0

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

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

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

Thalidomide	1
was	0
discontinued	0
in	0
55	0
patients	0
for	0
lack	0
of	0
therapeutic	0
response	0
.	0

0f	0
67	0
patients	0
initially	0
enrolled	0
,	0
24	0
remained	0
on	0
thalidomide	1
for	0
3	0
months	0
,	0
8	0
remained	0
at	0
6	0
months	0
,	0
and	0
3	0
remained	0
at	0
9	0
months	0
.	0

Six	0
patients	0
developed	0
neuropathy	3
.	0

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

0lder	0
age	0
and	0
cumulative	0
dose	0
were	0
possible	0
contributing	0
factors	0
.	0

Neuropathy	3
may	0
thus	0
be	0
a	0
common	0
complication	0
of	0
thalidomide	1
in	0
older	0
patients	0
.	0

The	0
SNAP	0
index	0
can	0
be	0
used	0
to	0
monitor	0
peripheral	3
neuropathy	4
,	0
but	0
not	0
for	0
early	0
detection	0
.	0

0verexpression	0
of	0
copper	1
/	0
zinc	1
-	0
superoxide	1
dismutase	0
protects	0
from	0
kanamycin	1
-	0
induced	0
hearing	3
loss	4
.	0

The	0
participation	0
of	0
reactive	0
oxygen	1
species	0
in	0
aminoglycoside	1
-	0
induced	0
ototoxicity	3
has	0
been	0
deduced	0
from	0
observations	0
that	0
aminoglycoside	1
-	0
iron	1
complexes	0
catalyze	0
the	0
formation	0
of	0
superoxide	1
radicals	0
in	0
vitro	0
and	0
that	0
antioxidants	0
attenuate	0
ototoxicity	3
in	0
vivo	0
.	0

We	0
therefore	0
hypothesized	0
that	0
overexpression	0
of	0
Cu	1
/	0
Zn	1
-	0
superoxide	1
dismutase	0
(	0
h	0
-	0
S0D1	0
)	0
should	0
protect	0
transgenic	0
mice	0
from	0
ototoxicity	3
.	0

Immunocytochemistry	0
confirmed	0
expression	0
of	0
h	0
-	0
S0D1	0
in	0
inner	0
ear	0
tissues	0
of	0
transgenic	0
C57BL	0
/	0
6	0
-	0
TgN	0
[	0
S0D1	0
]	0
3Cje	0
mice	0
.	0

Transgenic	0
and	0
nontransgenic	0
littermates	0
received	0
kanamycin	1
(	0
400	0
mg	0
/	0
kg	0
body	0
weight	0
/	0
day	0
)	0
for	0
10	0
days	0
beginning	0
on	0
day	0
10	0
after	0
birth	0
.	0

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

In	0
nontransgenic	0
animals	0
,	0
the	0
threshold	0
in	0
the	0
kanamycin	1
-	0
treated	0
group	0
was	0
45	0
-	0
50	0
dB	0
higher	0
than	0
in	0
saline	0
-	0
injected	0
controls	0
.	0

In	0
the	0
transgenic	0
group	0
,	0
kanamycin	1
increased	0
the	0
threshold	0
by	0
only	0
15	0
dB	0
over	0
the	0
respective	0
controls	0
.	0

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

The	0
protection	0
by	0
overexpression	0
of	0
superoxide	1
dismutase	0
supports	0
the	0
hypothesis	0
that	0
oxidant	0
stress	0
plays	0
a	0
significant	0
role	0
in	0
aminoglycoside	1
-	0
induced	0
ototoxicity	3
.	0

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

Fatty	3
liver	4
induced	0
by	0
tetracycline	1
in	0
the	0
rat	0
.	0

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

Dose	0
-	0
response	0
relationships	0
,	0
biochemical	0
mechanisms	0
,	0
and	0
sex	0
differences	0
in	0
the	0
experimental	0
fatty	3
liver	4
induced	0
by	0
tetracycline	1
were	0
studied	0
in	0
the	0
intact	0
rat	0
and	0
with	0
the	0
isolated	0
perfused	0
rat	0
liver	0
in	0
vitro	0
.	0

In	0
the	0
intact	0
male	0
and	0
female	0
rat	0
,	0
no	0
direct	0
relationship	0
was	0
observed	0
between	0
dose	0
of	0
tetracycline	1
and	0
hepatic	0
accumulation	0
of	0
triglyceride	1
.	0

With	0
provision	0
of	0
adequate	0
oleic	1
acid	2
as	0
a	0
substrate	0
for	0
the	0
isolated	0
perfused	0
liver	0
,	0
a	0
direct	0
relationship	0
was	0
observed	0
between	0
dose	0
of	0
tetracycline	1
and	0
both	0
accumulation	0
of	0
triglyceride	1
in	0
the	0
liver	0
and	0
depression	3
of	0
output	0
of	0
triglyceride	1
by	0
livers	0
from	0
male	0
and	0
female	0
rats	0
.	0

Marked	0
differences	0
were	0
observed	0
between	0
female	0
and	0
male	0
rats	0
with	0
regard	0
to	0
base	0
line	0
(	0
control	0
)	0
hepatic	0
concentration	0
of	0
triglyceride	1
and	0
output	0
of	0
triglyceride	1
.	0

Accumulation	0
of	0
hepatic	0
triglyceride	1
,	0
as	0
a	0
per	0
cent	0
of	0
control	0
values	0
,	0
in	0
response	0
to	0
graded	0
doses	0
of	0
tetracycline	1
,	0
did	0
not	0
differ	0
significantly	0
between	0
male	0
,	0
female	0
and	0
pregnant	0
rat	0
livers	0
.	0

However	0
,	0
livers	0
from	0
female	0
,	0
and	0
especially	0
pregnant	0
female	0
rats	0
,	0
were	0
strikingly	0
resistant	0
to	0
the	0
effects	0
of	0
tetracycline	1
on	0
depression	3
of	0
output	0
of	0
triglyceride	1
under	0
these	0
experimental	0
conditions	0
.	0

These	0
differences	0
between	0
the	0
sexes	0
could	0
not	0
be	0
related	0
to	0
altered	0
disposition	0
of	0
tetracycline	1
or	0
altered	0
uptake	0
of	0
oleic	1
acid	2
.	0

Depressed	0
hepatic	0
secretion	0
of	0
triglyceride	1
accounted	0
only	0
for	0
30	0
to	0
50	0
%	0
of	0
accumulated	0
hepatic	0
triglyceride	1
,	0
indicating	0
that	0
additional	0
mechanisms	0
must	0
be	0
involved	0
in	0
the	0
production	0
of	0
the	0
triglyceride	1
-	0
rich	0
fatty	3
liver	4
in	0
response	0
to	0
tetracycline	1
.	0

Prednisone	1
induces	0
anxiety	3
and	0
glial	0
cerebral	0
changes	0
in	0
rats	0
.	0

0BJECTIVE	0
:	0
To	0
assess	0
whether	0
prednisone	1
(	0
PDN	1
)	0
produces	0
anxiety	3
and	0
/	0
or	0
cerebral	0
glial	0
changes	0
in	0
rats	0
.	0

METH0DS	0
:	0
Male	0
Wistar	0
rats	0
were	0
studied	0
and	0
3	0
groups	0
were	0
formed	0
(	0
8	0
rats	0
per	0
group	0
)	0
.	0

The	0
moderate	0
-	0
dose	0
group	0
received	0
5	0
mg	0
/	0
kg	0
/	0
day	0
PDN	1
released	0
from	0
a	0
subcutaneous	0
implant	0
.	0

In	0
the	0
high	0
-	0
dose	0
group	0
,	0
implants	0
containing	0
PDN	1
equivalent	0
to	0
60	0
mg	0
/	0
kg	0
/	0
day	0
were	0
applied	0
.	0

In	0
the	0
control	0
group	0
implants	0
contained	0
no	0
PDN	1
.	0

Anxiety	3
was	0
assessed	0
using	0
an	0
open	0
field	0
and	0
elevated	0
plus	0
-	0
maze	0
devices	0
.	0

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

RESULTS	0
:	0
Anxiety	3
was	0
documented	0
in	0
both	0
groups	0
of	0
PDN	1
treated	0
rats	0
compared	0
with	0
controls	0
.	0

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

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

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

C0NCLUSI0N	0
:	0
Subacute	0
exposure	0
to	0
PDN	1
induced	0
anxiety	3
and	0
reactivity	0
of	0
microglia	0
.	0

The	0
relevance	0
of	0
these	0
features	0
for	0
patients	0
using	0
PDN	1
remains	0
to	0
be	0
elucidated	0
.	0

Phase	0
II	0
study	0
of	0
carboplatin	1
and	0
liposomal	0
doxorubicin	1
in	0
patients	0
with	0
recurrent	0
squamous	3
cell	4
carcinoma	4
of	4
the	4
cervix	4
.	0

BACKGR0UND	0
:	0
The	0
activity	0
of	0
the	0
combination	0
of	0
carboplatin	1
and	0
liposomal	0
doxorubicin	1
was	0
tested	0
in	0
a	0
Phase	0
II	0
study	0
of	0
patients	0
with	0
recurrent	0
cervical	3
carcinoma	4
.	0

METH0DS	0
:	0
The	0
combination	0
of	0
carboplatin	1
(	0
area	0
under	0
the	0
concentration	0
curve	0
[	0
AUC	0
]	0
,	0
5	0
)	0
and	0
liposomal	0
doxorubicin	1
(	0
Doxil	1
;	0
starting	0
dose	0
,	0
40	0
mg	0
/	0
m	0
(	0
2	0
)	0
)	0
was	0
administered	0
intravenously	0
every	0
28	0
days	0
to	0
37	0
patients	0
with	0
recurrent	0
squamous	3
cell	4
cervical	4
carcinoma	4
to	0
determine	0
antitumor	0
activity	0
and	0
toxicity	3
profile	0
.	0

RESULTS	0
:	0
Twenty	0
-	0
nine	0
patients	0
were	0
assessable	0
for	0
response	0
,	0
and	0
35	0
patients	0
were	0
assessable	0
for	0
toxicity	3
.	0

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

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

Four	0
patients	0
had	0
five	0
infusion	0
-	0
related	0
reactions	0
during	0
the	0
infusion	0
of	0
liposomal	0
doxorubicin	1
,	0
leading	0
to	0
treatment	0
discontinuation	0
in	0
three	0
patients	0
.	0

Grade	0
>	0
or	0
=	0
2	0
nonhematologic	0
toxicity	3
included	0
nausea	3
in	0
17	0
patients	0
,	0
emesis	3
in	0
14	0
patients	0
,	0
fatigue	3
in	0
9	0
patients	0
,	0
mucositis	3
and	0
/	0
or	0
stomatitis	3
in	0
8	0
patients	0
,	0
constipation	3
in	0
6	0
patients	0
,	0
weight	3
loss	4
in	0
5	0
patients	0
,	0
hand	3
-	4
foot	4
syndrome	4
in	0
2	0
patients	0
,	0
and	0
skin	3
reactions	4
in	0
3	0
patients	0
.	0

C0NCLUSI0NS	0
:	0
The	0
combination	0
of	0
carboplatin	1
and	0
liposomal	0
doxorubicin	1
has	0
modest	0
activity	0
in	0
patients	0
with	0
recurrent	0
cervical	3
carcinoma	4
.	0

Antimicrobial	0
-	0
induced	0
mania	3
(	0
antibiomania	3
)	0
:	0
a	0
review	0
of	0
spontaneous	0
reports	0
.	0

The	0
authors	0
reviewed	0
reported	0
cases	0
of	0
antibiotic	0
-	0
induced	0
manic	3
episodes	0
by	0
means	0
of	0
a	0
MEDLINE	0
and	0
PsychLit	0
search	0
for	0
reports	0
of	0
antibiotic	0
-	0
induced	0
mania	3
.	0

Unpublished	0
reports	0
were	0
requested	0
from	0
the	0
World	0
Health	0
0rganization	0
(	0
WH0	0
)	0
and	0
the	0
Food	0
and	0
Drug	0
Administration	0
(	0
FDA	0
)	0
.	0

Twenty	0
-	0
one	0
reports	0
of	0
antimicrobial	0
-	0
induced	0
mania	3
were	0
found	0
in	0
the	0
literature	0
.	0

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

The	0
WH0	0
reported	0
82	0
cases	0
.	0

0f	0
these	0
,	0
clarithromycin	1
was	0
implicated	0
in	0
23	0
(	0
27	0
.	0
6	0
%	0
)	0
cases	0
,	0
ciprofloxacin	1
in	0
12	0
(	0
14	0
.	0
4	0
%	0
)	0
cases	0
,	0
and	0
ofloxacin	1
in	0
10	0
(	0
12	0
%	0
)	0
cases	0
.	0

Cotrimoxazole	1
,	0
metronidazole	1
,	0
and	0
erythromycin	1
were	0
involved	0
in	0
15	0
reported	0
manic	3
episodes	0
.	0

Cases	0
reported	0
by	0
the	0
FDA	0
showed	0
clarithromycin	1
and	0
ciprofloxacin	1
to	0
be	0
the	0
most	0
frequently	0
associated	0
with	0
the	0
development	0
of	0
mania	3
.	0

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

Patients	0
have	0
an	0
increased	0
risk	0
of	0
developing	0
mania	3
while	0
being	0
treated	0
with	0
antimicrobials	0
.	0

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

Further	0
research	0
clearly	0
is	0
required	0
to	0
determine	0
the	0
incidence	0
of	0
antimicrobial	0
-	0
induced	0
mania	3
,	0
the	0
relative	0
risk	0
factors	0
of	0
developing	0
an	0
antimicrobial	0
-	0
induced	0
manic	3
episode	0
among	0
various	0
demographic	0
populations	0
,	0
and	0
the	0
incidence	0
of	0
patients	0
who	0
continue	0
to	0
have	0
persistent	0
affective	0
disorders	0
once	0
the	0
initial	0
episode	0
,	0
which	0
occurs	0
while	0
the	0
patient	0
is	0
taking	0
antibiotics	0
,	0
subsides	0
.	0

The	0
authors	0
elected	0
to	0
name	0
this	0
syndrome	0
"	0
antibiomania	3
.	0
"	0

Levodopa	1
-	0
induced	0
ocular	3
dyskinesias	4
in	0
Parkinson	3
'	4
s	4
disease	4
.	0

Levodopa	1
-	0
induced	0
ocular	3
dyskinesias	4
are	0
very	0
uncommon	0
.	0

Usually	0
they	0
occur	0
simultaneously	0
with	0
limb	0
peak	0
-	0
dose	0
choreatic	3
dyskinesias	4
.	0

We	0
report	0
on	0
a	0
patient	0
with	0
leftward	0
and	0
upward	0
deviations	0
of	0
gaze	0
during	0
the	0
peak	0
effect	0
of	0
levodopa	1
,	0
and	0
hypothesize	0
that	0
a	0
severe	0
dopaminergic	0
denervation	0
in	0
the	0
caudate	0
nucleus	0
is	0
needed	0
for	0
the	0
appearance	0
of	0
these	0
levodopa	1
-	0
induce	0
ocular	3
dyskinesias	4
.	0

A	0
comparison	0
of	0
glyceryl	1
trinitrate	2
with	0
diclofenac	1
for	0
the	0
treatment	0
of	0
primary	0
dysmenorrhea	3
:	0
an	0
open	0
,	0
randomized	0
,	0
cross	0
-	0
over	0
trial	0
.	0

Primary	0
dysmenorrhea	3
is	0
a	0
syndrome	0
characterized	0
by	0
painful	0
uterine	0
contractility	0
caused	0
by	0
a	0
hypersecretion	0
of	0
endometrial	0
prostaglandins	1
;	0
non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
drugs	0
are	0
the	0
first	0
choice	0
for	0
its	0
treatment	0
.	0

However	0
,	0
in	0
vivo	0
and	0
in	0
vitro	0
studies	0
have	0
demonstrated	0
that	0
myometrial	0
cells	0
are	0
also	0
targets	0
of	0
the	0
relaxant	0
effects	0
of	0
nitric	1
oxide	2
(	0
N0	1
)	0
.	0

The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
determine	0
the	0
efficacy	0
of	0
glyceryl	1
trinitrate	2
(	0
GTN	1
)	0
,	0
an	0
N0	1
donor	0
,	0
in	0
the	0
resolution	0
of	0
primary	0
dysmenorrhea	3
in	0
comparison	0
with	0
diclofenac	1
(	0
DCF	1
)	0
.	0

A	0
total	0
of	0
24	0
patients	0
with	0
the	0
diagnosis	0
of	0
severe	0
primary	0
dysmenorrhea	3
were	0
studied	0
during	0
two	0
consecutive	0
menstrual	0
cycles	0
.	0

In	0
an	0
open	0
,	0
cross	0
-	0
over	0
,	0
controlled	0
design	0
,	0
patients	0
were	0
randomized	0
to	0
receive	0
either	0
DCF	1
per	0
os	0
or	0
GTN	1
patches	0
the	0
first	0
days	0
of	0
menses	0
,	0
when	0
menstrual	0
cramps	0
became	0
unendurable	0
.	0

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

Patients	0
received	0
up	0
to	0
3	0
doses	0
/	0
day	0
of	0
50	0
mg	0
DCF	1
or	0
2	0
.	0
5	0
mg	0
/	0
24	0
h	0
transdermal	0
GTN	1
for	0
the	0
first	0
3	0
days	0
of	0
the	0
cycle	0
,	0
according	0
to	0
their	0
needs	0
.	0

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

The	0
difference	0
in	0
pain	3
intensity	0
score	0
(	0
DPI	0
)	0
was	0
the	0
main	0
outcome	0
variable	0
.	0

Both	0
treatments	0
significantly	0
reduced	0
DPI	0
by	0
the	0
30th	0
minute	0
(	0
GTN	1
,	0
-	0
12	0
.	0
8	0
+	0
/	0
-	0
17	0
.	0
9	0
;	0
DCF	1
,	0
-	0
18	0
.	0
9	0
+	0
/	0
-	0
16	0
.	0
6	0
)	0
.	0

However	0
,	0
DCF	1
continued	0
to	0
be	0
effective	0
in	0
reducing	0
pelvic	3
pain	4
for	0
two	0
hours	0
,	0
whereas	0
GTN	1
scores	0
remained	0
more	0
or	0
less	0
stable	0
after	0
30	0
min	0
and	0
significantly	0
higher	0
than	0
those	0
for	0
DFC	0
(	0
after	0
one	0
hour	0
:	0
GTN	1
,	0
-	0
12	0
.	0
8	0
+	0
/	0
-	0
17	0
.	0
9	0
;	0
DFC	0
,	0
-	0
18	0
.	0
9	0
+	0
/	0
-	0
16	0
.	0
6	0
and	0
after	0
two	0
hours	0
:	0
GTN	1
,	0
-	0
23	0
.	0
7	0
+	0
/	0
-	0
20	0
.	0
5	0
;	0
DFC	0
,	0
-	0
59	0
.	0
7	0
+	0
/	0
-	0
17	0
.	0
9	0
,	0
p	0
=	0
0	0
.	0
0001	0
)	0
.	0

Low	3
back	4
pain	4
was	0
also	0
relieved	0
by	0
both	0
drugs	0
.	0

Headache	3
was	0
significantly	0
increased	0
by	0
GTN	1
but	0
not	0
by	0
DCF	1
.	0

Eight	0
patients	0
stopped	0
using	0
GTN	1
because	0
headache	3
-	0
-	0
attributed	0
to	0
its	0
use	0
-	0
-	0
became	0
intolerable	0
.	0

These	0
findings	0
indicate	0
that	0
GTN	1
has	0
a	0
reduced	0
efficacy	0
and	0
tolerability	0
by	0
comparison	0
with	0
DCF	1
in	0
the	0
treatment	0
of	0
primary	0
dysmenorrhea	3
.	0

Temocapril	1
,	0
a	0
long	0
-	0
acting	0
non	0
-	0
SH	0
group	0
angiotensin	1
converting	0
enzyme	0
inhibitor	0
,	0
modulates	0
glomerular	3
injury	4
in	0
chronic	0
puromycin	1
aminonucleoside	2
nephrosis	3
.	0

The	0
purpose	0
of	0
the	0
present	0
study	0
was	0
to	0
determine	0
whether	0
chronic	0
administration	0
of	0
temocapril	1
,	0
a	0
long	0
-	0
acting	0
non	0
-	0
SH	0
group	0
angiotensin	1
converting	0
enzyme	0
(	0
ACE	0
)	0
inhibitor	0
,	0
reduced	0
proteinuria	3
,	0
inhibited	0
glomerular	0
hypertrophy	3
and	0
prevented	0
glomerulosclerosis	3
in	0
chronic	0
puromycin	1
aminonucleoside	2
(	0
PAN	1
)	0
-	0
induced	0
nephrotic	3
rats	0
.	0

Nephrosis	3
was	0
induced	0
by	0
injection	0
of	0
PAN	1
(	0
15mg	0
/	0
100g	0
body	0
weight	0
)	0
in	0
male	0
Sprague	0
-	0
Dawley	0
(	0
SD	0
)	0
rats	0
.	0

Four	0
groups	0
were	0
used	0
,	0
i	0
)	0
the	0
PAN	1
group	0
(	0
14	0
)	0
,	0
ii	0
)	0
PAN	1
/	0
temocapril	1
(	0
13	0
)	0
,	0
iii	0
)	0
temocapril	1
(	0
14	0
)	0
and	0
iv	0
)	0
untreated	0
controls	0
(	0
15	0
)	0
.	0

Temocapril	1
(	0
8	0
mg	0
/	0
kg	0
/	0
day	0
)	0
was	0
administered	0
to	0
the	0
rats	0
which	0
were	0
killed	0
at	0
weeks	0
4	0
,	0
14	0
or	0
20	0
.	0

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

Systolic	0
BP	0
in	0
the	0
PAN	1
group	0
was	0
significantly	0
high	0
at	0
4	0
,	0
14	0
and	0
20	0
weeks	0
,	0
but	0
was	0
normal	0
in	0
the	0
PAN	1
/	0
temocapril	1
group	0
.	0

Urinary	0
protein	0
excretion	0
in	0
the	0
PAN	1
group	0
increased	0
significantly	0
,	0
peaking	0
at	0
8	0
days	0
,	0
then	0
decreased	0
at	0
4	0
weeks	0
,	0
but	0
rose	0
again	0
significantly	0
at	0
14	0
and	0
20	0
weeks	0
.	0

Temocapril	1
did	0
not	0
attenuate	0
proteinuria	3
at	0
8	0
days	0
,	0
but	0
it	0
did	0
markedly	0
lower	0
it	0
from	0
weeks	0
4	0
to	0
20	0
.	0

The	0
glomerulosclerosis	3
index	0
(	0
GSI	0
)	0
was	0
6	0
.	0
21	0
%	0
at	0
4	0
weeks	0
and	0
respectively	0
25	0
.	0
35	0
%	0
and	0
30	0
.	0
49	0
%	0
at	0
14	0
and	0
20	0
weeks	0
in	0
the	0
PAN	1
group	0
.	0

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

The	0
ratio	0
of	0
glomerular	0
tuft	0
area	0
to	0
the	0
area	0
of	0
Bowman	0
'	0
s	0
capsules	0
(	0
GT	0
/	0
BC	0
)	0
in	0
the	0
PAN	1
group	0
was	0
significantly	0
increased	0
,	0
but	0
it	0
was	0
significantly	0
lower	0
in	0
the	0
PAN	1
/	0
temocapril	1
group	0
.	0

It	0
appears	0
that	0
temocapril	1
was	0
effective	0
in	0
retarding	0
renal	0
progression	0
and	0
protected	0
renal	0
function	0
in	0
PAN	1
neprotic	3
rats	0
.	0

Pulmonary	3
hypertension	4
after	0
ibuprofen	1
prophylaxis	0
in	0
very	0
preterm	0
infants	0
.	0

We	0
report	0
three	0
cases	0
of	0
severe	0
hypoxaemia	3
after	0
ibuprofen	1
administration	0
during	0
a	0
randomised	0
controlled	0
trial	0
of	0
prophylactic	0
treatment	0
of	0
patent	3
ductus	4
arteriosus	4
with	0
ibuprofen	1
in	0
premature	0
infants	0
born	0
at	0
less	0
than	0
28	0
weeks	0
of	0
gestation	0
.	0

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

Hypoxaemia	3
resolved	0
quickly	0
on	0
inhaled	0
nitric	1
oxide	2
therapy	0
.	0

We	0
suggest	0
that	0
investigators	0
involved	0
in	0
similar	0
trials	0
pay	0
close	0
attention	0
to	0
pulmonary	0
pressure	0
if	0
hypoxaemia	3
occurs	0
after	0
prophylactic	0
administration	0
of	0
ibuprofen	1
.	0

Hyponatremia	3
and	0
syndrome	3
of	4
inappropriate	4
anti	4
-	4
diuretic	4
hormone	4
reported	0
with	0
the	0
use	0
of	0
Vincristine	1
:	0
an	0
over	0
-	0
representation	0
of	0
Asians	0
?	0

PURP0SE	0
:	0
This	0
retrospective	0
study	0
used	0
a	0
pharmaceutical	0
company	0
'	0
s	0
global	0
safety	0
database	0
to	0
determine	0
the	0
reporting	0
rate	0
of	0
hyponatremia	3
and	0
/	0
or	0
syndrome	3
of	4
inappropriate	4
secretion	4
of	4
anti	4
-	4
diuretic	4
hormone	4
(	0
SIADH	3
)	0
among	0
vincristine	1
-	0
treated	0
patients	0
and	0
to	0
explore	0
the	0
possibility	0
of	0
at	0
-	0
risk	0
population	0
subgroups	0
.	0

METH0D	0
:	0
We	0
searched	0
the	0
Eli	0
Lilly	0
and	0
Company	0
'	0
s	0
computerized	0
adverse	0
event	0
database	0
for	0
all	0
reported	0
cases	0
of	0
hyponatremia	3
and	0
/	0
or	0
SIADH	3
as	0
of	0
1	0
November	0
1999	0
that	0
had	0
been	0
reported	0
during	0
the	0
use	0
of	0
vincristine	1
.	0

RESULTS	0
:	0
A	0
total	0
of	0
76	0
cases	0
of	0
hyponatremia	3
and	0
/	0
or	0
SIADH	3
associated	0
with	0
vincristine	1
use	0
were	0
identified	0
.	0

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

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

Approximately	0
75	0
%	0
of	0
the	0
patients	0
were	0
receiving	0
treatment	0
for	0
leukemia	3
or	0
lymphoma	3
.	0

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

C0NCLUSI0N	0
:	0
0ur	0
data	0
suggest	0
that	0
Asian	0
patients	0
may	0
be	0
at	0
increased	0
risk	0
of	0
hyponatremia	3
and	0
/	0
or	0
SIADH	3
associated	0
with	0
vincristine	1
use	0
.	0

Although	0
the	0
overall	0
reported	0
rate	0
of	0
SIADH	3
associated	0
with	0
vincristine	1
is	0
very	0
low	0
,	0
physicians	0
caring	0
for	0
Asian	0
oncology	0
patients	0
should	0
be	0
aware	0
of	0
this	0
potential	0
serious	0
but	0
reversible	0
adverse	0
event	0
.	0

Delayed	0
toxicity	3
of	0
cyclophosphamide	1
on	0
the	0
bladder	0
of	0
DBA	0
/	0
2	0
and	0
C57BL	0
/	0
6	0
female	0
mouse	0
.	0

The	0
present	0
study	0
describes	0
the	0
delayed	0
development	0
of	0
a	0
severe	0
bladder	0
pathology	0
in	0
a	0
susceptible	0
strain	0
of	0
mice	0
(	0
DBA	0
/	0
2	0
)	0
but	0
not	0
in	0
a	0
resistant	0
strain	0
(	0
C57BL	0
/	0
6	0
)	0
when	0
both	0
were	0
treated	0
with	0
a	0
single	0
300	0
mg	0
/	0
kg	0
dose	0
of	0
cyclophosphamide	1
(	0
CY	1
)	0
.	0

Inbred	0
DBA	0
/	0
2	0
and	0
C57BL	0
/	0
6	0
female	0
mice	0
were	0
injected	0
with	0
CY	1
,	0
and	0
the	0
effect	0
of	0
the	0
drug	0
on	0
the	0
bladder	0
was	0
assessed	0
during	0
100	0
days	0
by	0
light	0
microscopy	0
using	0
different	0
staining	0
procedures	0
,	0
and	0
after	0
30	0
days	0
by	0
conventional	0
electron	0
microscopy	0
.	0

Early	0
CY	1
toxicity	3
caused	0
a	0
typical	0
haemorrhagic	3
cystitis	3
in	0
both	0
strains	0
that	0
was	0
completely	0
repaired	0
in	0
about	0
7	0
-	0
10	0
days	0
.	0

After	0
30	0
days	0
of	0
CY	1
injection	0
ulcerous	0
and	0
non	0
-	0
ulcerous	0
forms	0
of	0
chronic	0
cystitis	3
appeared	0
in	0
86	0
%	0
of	0
DBA	0
/	0
2	0
mice	0
but	0
only	0
in	0
4	0
%	0
of	0
C57BL	0
/	0
6	0
mice	0
.	0

Delayed	0
cystitis	3
was	0
characterized	0
by	0
infiltration	0
and	0
transepithelial	0
passage	0
into	0
the	0
lumen	0
of	0
inflammatory	0
cells	0
and	0
by	0
frequent	0
exfoliation	0
of	0
the	0
urothelium	0
.	0

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

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

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

Delayed	0
cystitis	3
still	0
persisted	0
in	0
DBA	0
/	0
2	0
mice	0
100	0
days	0
after	0
treatment	0
.	0

These	0
results	0
indicate	0
that	0
delayed	0
toxicity	3
of	0
CY	1
in	0
female	0
DBA	0
/	0
2	0
mice	0
causes	0
a	0
bladder	0
pathology	0
that	0
is	0
not	0
observed	0
in	0
C57BL	0
/	0
6	0
mice	0
.	0

This	0
pathology	0
resembles	0
interstitial	3
cystitis	4
in	0
humans	0
and	0
could	0
perhaps	0
be	0
used	0
as	0
an	0
animal	0
model	0
for	0
studies	0
on	0
the	0
disease	0
.	0

High	0
-	0
dose	0
5	1
-	2
fluorouracil	2
/	0
folinic	1
acid	2
in	0
combination	0
with	0
three	0
-	0
weekly	0
mitomycin	1
C	2
in	0
the	0
treatment	0
of	0
advanced	0
gastric	3
cancer	4
.	0

A	0
phase	0
II	0
study	0
.	0

BACKGR0UND	0
:	0
The	0
24	0
-	0
hour	0
continuous	0
infusion	0
of	0
5	1
-	2
fluorouracil	2
(	0
5	1
-	2
FU	2
)	0
and	0
folinic	1
acid	2
(	0
FA	1
)	0
as	0
part	0
of	0
several	0
new	0
multidrug	0
chemotherapy	0
regimens	0
in	0
advanced	0
gastric	3
cancer	4
(	0
AGC	3
)	0
has	0
shown	0
to	0
be	0
effective	0
,	0
with	0
low	0
toxicity	3
.	0

In	0
a	0
previous	0
phase	0
II	0
study	0
with	0
3	0
-	0
weekly	0
bolus	0
5	1
-	2
FU	2
,	0
FA	1
and	0
mitomycin	1
C	2
(	0
MMC	1
)	0
we	0
found	0
a	0
low	0
toxicity	3
rate	0
and	0
response	0
rates	0
comparable	0
to	0
those	0
of	0
regimens	0
such	0
as	0
ELF	0
,	0
FAM	0
or	0
FAMTX	0
,	0
and	0
a	0
promising	0
median	0
overall	0
survival	0
.	0

In	0
order	0
to	0
improve	0
this	0
MMC	1
-	0
dependent	0
schedule	0
we	0
initiated	0
a	0
phase	0
II	0
study	0
with	0
high	0
-	0
dose	0
5	1
-	2
FU	2
/	0
FA	1
and	0
3	0
-	0
weekly	0
bolus	0
MMC	1
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
From	0
February	0
,	0
1998	0
to	0
September	0
,	0
2000	0
we	0
recruited	0
33	0
patients	0
with	0
AGC	3
to	0
receive	0
weekly	0
24	0
-	0
hour	0
5	1
-	2
FU	2
2	0
,	0
600	0
mg	0
/	0
m	0
(	0
2	0
)	0
preceded	0
by	0
2	0
-	0
hour	0
FA	1
500	0
mg	0
/	0
m	0
(	0
2	0
)	0
for	0
6	0
weeks	0
,	0
followed	0
by	0
a	0
2	0
-	0
week	0
rest	0
period	0
.	0

Bolus	0
MMC	1
10	0
mg	0
/	0
m	0
(	0
2	0
)	0
was	0
added	0
in	0
3	0
-	0
weekly	0
intervals	0
.	0

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

Patients	0
'	0
characteristics	0
were	0
:	0
male	0
/	0
female	0
ratio	0
20	0
/	0
13	0
;	0
median	0
age	0
57	0
(	0
27	0
-	0
75	0
)	0
years	0
;	0
median	0
WH0	0
status	0
1	0
(	0
0	0
-	0
2	0
)	0
.	0

18	0
patients	0
had	0
a	0
primary	0
AGC	3
,	0
and	0
15	0
showed	0
a	0
relapsed	0
AGC	3
.	0

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

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

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

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

Two	0
patients	0
developed	0
hemolytic	3
-	4
uremic	4
syndrome	4
(	0
HUS	3
)	0
.	0

C0NCLUSI0NS	0
:	0
High	0
-	0
dose	0
5	1
-	2
FU	2
/	0
FA	1
/	0
MMC	1
is	0
an	0
effective	0
and	0
well	0
-	0
tolerated	0
outpatient	0
regimen	0
for	0
AGC	3
(	0
objective	0
response	0
rate	0
54	0
.	0
6	0
%	0
)	0
.	0

It	0
may	0
serve	0
as	0
an	0
alternative	0
to	0
cisplatin	1
-	0
containing	0
regimens	0
;	0
however	0
,	0
it	0
has	0
to	0
be	0
considered	0
that	0
possibly	0
HUS	3
may	0
occur	0
.	0

Persistent	0
sterile	0
leukocyturia	3
is	0
associated	0
with	0
impaired	3
renal	4
function	4
in	0
human	3
immunodeficiency	4
virus	4
type	4
1	4
-	4
infected	4
children	0
treated	0
with	0
indinavir	1
.	0

BACKGR0UND	0
:	0
Prolonged	0
administration	0
of	0
indinavir	1
is	0
associated	0
with	0
the	0
occurrence	0
of	0
a	0
variety	0
of	0
renal	0
complications	0
in	0
adults	0
.	0

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

DESIGN	0
:	0
A	0
prospective	0
study	0
to	0
monitor	0
indinavir	1
-	0
related	0
nephrotoxicity	3
in	0
a	0
cohort	0
of	0
30	0
human	3
immunodeficiency	4
virus	4
type	4
1	4
-	4
infected	4
children	0
treated	0
with	0
indinavir	1
.	0

METH0DS	0
:	0
Urinary	0
pH	0
,	0
albumin	0
,	0
creatinine	1
,	0
the	0
presence	0
of	0
erythrocytes	0
,	0
leukocytes	0
,	0
bacteria	0
and	0
crystals	0
,	0
and	0
culture	0
were	0
analyzed	0
every	0
3	0
months	0
for	0
96	0
weeks	0
.	0

Serum	0
creatinine	1
levels	0
were	0
routinely	0
determined	0
at	0
the	0
same	0
time	0
points	0
.	0

Steady	0
-	0
state	0
pharmacokinetics	0
of	0
indinavir	1
were	0
done	0
at	0
week	0
4	0
after	0
the	0
initiation	0
of	0
indinavir	1
.	0

RESULTS	0
:	0
The	0
cumulative	0
incidence	0
of	0
persistent	0
sterile	0
leukocyturia	3
(	0
>	0
or	0
=	0
75	0
cells	0
/	0
micro	0
L	0
in	0
at	0
least	0
2	0
consecutive	0
visits	0
)	0
after	0
96	0
weeks	0
was	0
53	0
%	0
.	0

Persistent	0
sterile	0
leukocyturia	3
was	0
frequently	0
associated	0
with	0
a	0
mild	0
increase	0
in	0
the	0
urine	0
albumin	0
/	0
creatinine	1
ratio	0
and	0
by	0
microscopic	0
hematuria	3
.	0

The	0
cumulative	0
incidence	0
of	0
serum	0
creatinine	1
levels	0
>	0
50	0
%	0
above	0
normal	0
was	0
33	0
%	0
after	0
96	0
weeks	0
.	0

Children	0
with	0
persistent	0
sterile	0
leukocyturia	3
more	0
frequently	0
had	0
serum	0
creatinine	1
levels	0
of	0
50	0
%	0
above	0
normal	0
than	0
those	0
children	0
without	0
persistent	0
sterile	0
leukocyturia	3
.	0

In	0
children	0
younger	0
than	0
5	0
.	0
6	0
years	0
,	0
persistent	0
sterile	0
leukocyturia	3
was	0
significantly	0
more	0
frequent	0
than	0
in	0
older	0
children	0
.	0

A	0
higher	0
cumulative	0
incidence	0
of	0
persistent	0
leukocyturia	3
was	0
found	0
in	0
children	0
with	0
an	0
area	0
under	0
the	0
curve	0
>	0
19	0
mg	0
/	0
L	0
x	0
h	0
or	0
a	0
peak	0
serum	0
level	0
of	0
indinavir	1
>	0
12	0
mg	0
/	0
L	0
.	0

In	0
4	0
children	0
,	0
indinavir	1
was	0
discontinued	0
because	0
of	0
nephrotoxicity	3
.	0

Subsequently	0
,	0
the	0
serum	0
creatinine	1
levels	0
decreased	0
,	0
the	0
urine	0
albumin	0
/	0
creatinine	1
ratios	0
returned	0
to	0
zero	0
,	0
and	0
the	0
leukocyturia	3
disappeared	0
within	0
3	0
months	0
.	0

C0NCLUSI0NS	0
:	0
Children	0
treated	0
with	0
indinavir	1
have	0
a	0
high	0
cumulative	0
incidence	0
of	0
persistent	0
sterile	0
leukocyturia	3
.	0

Children	0
with	0
persistent	0
sterile	0
leukocyturia	3
more	0
frequently	0
had	0
an	0
increase	0
in	0
serum	0
creatinine	1
levels	0
of	0
>	0
50	0
%	0
above	0
normal	0
.	0

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

The	0
impairment	3
of	4
the	4
renal	4
function	4
in	0
these	0
children	0
occurred	0
in	0
the	0
absence	0
of	0
clinical	0
symptoms	0
of	0
nephrolithiasis	3
.	0

Indinavir	1
-	0
associated	0
nephrotoxicity	3
must	0
be	0
monitored	0
closely	0
,	0
especially	0
in	0
children	0
with	0
risk	0
factors	0
such	0
as	0
persistent	0
sterile	0
leukocyturia	3
,	0
age	0
<	0
5	0
.	0
6	0
years	0
,	0
an	0
area	0
under	0
the	0
curve	0
of	0
indinavir	1
>	0
19	0
mg	0
/	0
L	0
x	0
h	0
,	0
and	0
a	0
C	0
(	0
max	0
)	0
>	0
12	0
mg	0
/	0
L	0
.	0

Utility	0
of	0
troponin	0
I	0
in	0
patients	0
with	0
cocaine	1
-	0
associated	0
chest	3
pain	4
.	0

Baseline	0
electrocardiogram	0
abnormalities	0
and	0
market	0
elevations	0
not	0
associated	0
with	0
myocardial	3
necrosis	4
make	0
accurate	0
diagnosis	0
of	0
myocardial	3
infarction	4
(	0
MI	3
)	0
difficult	0
in	0
patients	0
with	0
cocaine	1
-	0
associated	0
chest	3
pain	4
.	0

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

0BJECTIVE	0
:	0
To	0
assess	0
outcomes	0
based	0
on	0
troponin	0
positivity	0
in	0
patients	0
with	0
cocaine	1
chest	3
pain	4
admitted	0
for	0
exclusion	0
of	0
MI	3
.	0

METH0DS	0
:	0
0utcomes	0
were	0
examined	0
in	0
patients	0
admitted	0
for	0
possible	0
MI	3
after	0
cocaine	1
use	0
.	0

All	0
patients	0
underwent	0
a	0
rapid	0
rule	0
-	0
in	0
protocol	0
that	0
included	0
serial	0
sampling	0
of	0
creatine	1
kinase	0
(	0
CK	0
)	0
,	0
CK	0
-	0
MB	0
,	0
and	0
cardiac	0
troponin	0
I	0
(	0
cTnI	0
)	0
over	0
eight	0
hours	0
.	0

0utcomes	0
included	0
CK	0
-	0
MB	0
MI	3
(	0
CK	0
-	0
MB	0
>	0
or	0
=	0
8	0
ng	0
/	0
mL	0
with	0
a	0
relative	0
index	0
[	0
(	0
CK	0
-	0
MB	0
x	0
100	0
)	0
/	0
total	0
CK	0
]	0
>	0
or	0
=	0
4	0
,	0
cardiac	3
death	4
,	0
and	0
significant	0
coronary	3
disease	4
(	0
>	0
or	0
=	0
50	0
%	0
)	0
.	0

RESULTS	0
:	0
0f	0
the	0
246	0
admitted	0
patients	0
,	0
34	0
(	0
14	0
%	0
)	0
met	0
CK	0
-	0
MB	0
criteria	0
for	0
MI	3
and	0
38	0
(	0
16	0
%	0
)	0
had	0
cTnI	0
elevations	0
.	0

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

Three	0
of	0
the	0
four	0
patients	0
without	0
significant	0
disease	0
who	0
had	0
cTnI	0
elevations	0
met	0
CK	0
-	0
MB	0
criteria	0
for	0
MI	3
,	0
and	0
the	0
other	0
had	0
a	0
peak	0
CK	0
-	0
MB	0
level	0
of	0
13	0
ng	0
/	0
mL	0
.	0

Sensitivities	0
,	0
specificities	0
,	0
and	0
positive	0
and	0
negative	0
likelihood	0
ratios	0
for	0
predicting	0
cardiac	3
death	4
or	0
significant	0
disease	0
were	0
high	0
for	0
both	0
CK	0
-	0
MB	0
MI	3
and	0
cTnI	0
and	0
were	0
not	0
significantly	0
different	0
.	0

C0NCLUSI0NS	0
:	0
Most	0
patients	0
with	0
cTnI	0
elevations	0
meet	0
CK	0
-	0
MB	0
criteria	0
for	0
MI	3
,	0
as	0
well	0
as	0
have	0
a	0
high	0
incidence	0
of	0
underlying	0
significant	0
disease	0
.	0

Troponin	0
appears	0
to	0
have	0
an	0
equivalent	0
diagnostic	0
accuracy	0
compared	0
with	0
CK	0
-	0
MB	0
for	0
diagnosing	0
necrosis	3
in	0
patients	0
with	0
cocaine	1
-	0
associated	0
chest	3
pain	4
and	0
suspected	0
MI	3
.	0

Acute	0
interstitial	3
nephritis	4
due	0
to	0
nicergoline	1
(	0
Sermion	1
)	0
.	0

We	0
report	0
a	0
case	0
of	0
acute	0
interstitial	3
nephritis	4
(	0
AIN	3
)	0
due	0
to	0
nicergoline	1
(	0
Sermion	1
)	0
.	0

A	0
50	0
-	0
year	0
-	0
old	0
patient	0
admitted	0
to	0
our	0
hospital	0
for	0
fever	3
and	0
acute	3
renal	4
failure	4
.	0

Before	0
admission	0
,	0
he	0
had	0
been	0
taking	0
nicergoline	1
and	0
bendazac	1
lysine	2
due	0
to	0
retinal	3
vein	4
occlusion	4
at	0
ophthalmologic	0
department	0
.	0

Thereafter	0
,	0
he	0
experienced	0
intermittent	0
fever	3
and	0
skin	3
rash	4
.	0

0n	0
admission	0
,	0
clinical	0
symptoms	0
(	0
i	0
.	0
e	0
.	0
arthralgia	3
and	0
fever	3
)	0
and	0
laboratory	0
findings	0
(	0
i	0
.	0
e	0
.	0
eosinophilia	3
and	0
renal	3
failure	4
)	0
suggested	0
AIN	3
,	0
and	0
which	0
was	0
confirmed	0
by	0
pathologic	0
findings	0
on	0
renal	0
biopsy	0
.	0

A	0
lymphocyte	0
transformation	0
test	0
demonstrated	0
a	0
positive	0
result	0
against	0
nicergoline	1
.	0

Treatment	0
was	0
consisted	0
of	0
withdrawal	0
of	0
nicergoline	1
and	0
intravenous	0
methylprednisolone	1
,	0
and	0
his	0
renal	0
function	0
was	0
completely	0
recovered	0
.	0

To	0
our	0
knowledge	0
,	0
this	0
is	0
the	0
first	0
report	0
of	0
nicergoline	1
-	0
associated	0
AIN	3
.	0

Neuroleptic	3
malignant	4
syndrome	4
complicated	0
by	0
massive	0
intestinal	0
bleeding	3
in	0
a	0
patient	0
with	0
chronic	3
renal	4
failure	4
.	0

A	0
patient	0
with	0
chronic	3
renal	4
failure	4
(	0
CRF	3
)	0
developed	0
neuroleptic	3
malignant	4
syndrome	4
(	0
NMS	3
)	0
after	0
administration	0
of	0
risperidone	1
and	0
levomepromazine	1
.	0

In	0
addition	0
to	0
the	0
typical	0
symptoms	0
of	0
NMS	3
,	0
massive	0
intestinal	0
bleeding	3
was	0
observed	0
during	0
the	0
episode	0
.	0

This	0
report	0
suggests	0
that	0
NMS	3
in	0
a	0
patient	0
with	0
CRF	3
may	0
be	0
complicated	0
by	0
intestinal	0
bleeding	3
and	0
needs	0
special	0
caution	0
for	0
this	0
complication	0
.	0

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

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

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

Adrenaline	1
-	0
induced	0
hypertension	3
was	0
used	0
to	0
destroy	0
the	0
BBB	0
,	0
which	0
was	0
evaluated	0
using	0
triphenyltetrazolium	1
(	0
TTC	1
)	0
staining	0
of	0
the	0
brain	0
slices	0
just	0
after	0
giving	0
adrenaline	1
for	0
30	0
s	0
.	0

In	0
normal	0
rats	0
,	0
the	0
whole	0
brain	0
sections	0
exhibited	0
complete	0
staining	0
with	0
TTC	1
.	0

After	0
adrenaline	1
infusion	0
for	0
30	0
s	0
,	0
there	0
were	0
large	0
unstained	0
areas	0
in	0
the	0
left	0
brain	0
in	0
right	0
-	0
pawed	0
animals	0
,	0
and	0
vice	0
versa	0
in	0
left	0
-	0
pawed	0
animals	0
.	0

Similar	0
results	0
were	0
obtained	0
in	0
seizure	3
-	0
induced	0
breakdown	0
of	0
BBB	0
.	0

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

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

Carvedilol	1
protects	0
against	0
doxorubicin	1
-	0
induced	0
mitochondrial	0
cardiomyopathy	3
.	0

Several	0
cytopathic	0
mechanisms	0
have	0
been	0
suggested	0
to	0
mediate	0
the	0
dose	0
-	0
limiting	0
cumulative	0
and	0
irreversible	0
cardiomyopathy	3
caused	0
by	0
doxorubicin	1
.	0

Recent	0
evidence	0
indicates	0
that	0
oxidative	0
stress	0
and	0
mitochondrial	3
dysfunction	4
are	0
key	0
factors	0
in	0
the	0
pathogenic	0
process	0
.	0

The	0
objective	0
of	0
this	0
investigation	0
was	0
to	0
test	0
the	0
hypothesis	0
that	0
carvedilol	1
,	0
a	0
nonselective	0
beta	0
-	0
adrenergic	0
receptor	0
antagonist	0
with	0
potent	0
antioxidant	0
properties	0
,	0
protects	0
against	0
the	0
cardiac	0
and	0
hepatic	0
mitochondrial	0
bioenergetic	0
dysfunction	0
associated	0
with	0
subchronic	0
doxorubicin	1
toxicity	3
.	0

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

Heart	0
mitochondria	0
isolated	0
from	0
doxorubicin	1
-	0
treated	0
rats	0
exhibited	0
depressed	0
rates	0
for	0
state	0
3	0
respiration	0
(	0
336	0
+	0
/	0
-	0
26	0
versus	0
425	0
+	0
/	0
-	0
53	0
natom	0
0	0
/	0
min	0
/	0
mg	0
protein	0
)	0
and	0
a	0
lower	0
respiratory	0
control	0
ratio	0
(	0
RCR	0
)	0
(	0
4	0
.	0
3	0
+	0
/	0
-	0
0	0
.	0
6	0
versus	0
5	0
.	0
8	0
+	0
/	0
-	0
0	0
.	0
4	0
)	0
compared	0
with	0
cardiac	0
mitochondria	0
isolated	0
from	0
saline	0
-	0
treated	0
rats	0
.	0

Mitochondrial	0
calcium	1
-	0
loading	0
capacity	0
and	0
the	0
activity	0
of	0
NADH	0
-	0
dehydrogenase	0
were	0
also	0
suppressed	0
in	0
cardiac	0
mitochondria	0
from	0
doxorubicin	1
-	0
treated	0
rats	0
.	0

Doxorubicin	1
treatment	0
also	0
caused	0
a	0
decrease	0
in	0
RCR	0
for	0
liver	0
mitochondria	0
(	0
3	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
9	0
versus	0
5	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
7	0
for	0
control	0
rats	0
)	0
and	0
inhibition	0
of	0
hepatic	0
cytochrome	0
oxidase	0
activity	0
.	0

Coadministration	0
of	0
carvedilol	1
decreased	0
the	0
extent	0
of	0
cellular	0
vacuolization	0
in	0
cardiac	0
myocytes	0
and	0
prevented	0
the	0
inhibitory	0
effect	0
of	0
doxorubicin	1
on	0
mitochondrial	0
respiration	0
in	0
both	0
heart	0
and	0
liver	0
.	0

Carvedilol	1
also	0
prevented	0
the	0
decrease	0
in	0
mitochondrial	0
Ca	1
(	0
2	0
+	0
)	0
loading	0
capacity	0
and	0
the	0
inhibition	0
of	0
the	0
respiratory	0
complexes	0
of	0
heart	0
mitochondria	0
caused	0
by	0
doxorubicin	1
.	0

Carvedilol	1
by	0
itself	0
did	0
not	0
affect	0
any	0
of	0
the	0
parameters	0
measured	0
for	0
heart	0
or	0
liver	0
mitochondria	0
.	0

It	0
is	0
concluded	0
that	0
this	0
protection	0
by	0
carvedilol	1
against	0
both	0
the	0
structural	0
and	0
functional	0
cardiac	0
tissue	0
damage	0
may	0
afford	0
significant	0
clinical	0
advantage	0
in	0
minimizing	0
the	0
dose	0
-	0
limiting	0
mitochondrial	3
dysfunction	4
and	0
cardiomyopathy	3
that	0
accompanies	0
long	0
-	0
term	0
doxorubicin	1
therapy	0
in	0
cancer	3
patients	0
.	0

Cocaine	1
-	0
induced	0
hyperactivity	3
is	0
more	0
influenced	0
by	0
adenosine	1
receptor	0
agonists	0
than	0
amphetamine	1
-	0
induced	0
hyperactivity	3
.	0

The	0
influence	0
of	0
adenosine	1
receptor	0
agonists	0
and	0
antagonists	0
on	0
cocaine	1
-	0
and	0
amphetamine	1
-	0
induced	0
hyperactivity	3
was	0
examined	0
in	0
mice	0
.	0

All	0
adenosine	1
receptor	0
agonists	0
significantly	0
decreased	3
the	4
locomotor	4
activity	4
in	0
mice	0
,	0
and	0
the	0
effects	0
were	0
dose	0
-	0
dependent	0
.	0

It	0
seems	0
that	0
adenosine	1
A1	0
and	0
A2	0
receptors	0
might	0
be	0
involved	0
in	0
this	0
reaction	0
.	0

Moreover	0
,	0
all	0
adenosine	1
receptor	0
agonists	0
:	0
2	1
-	2
p	2
-	2
(	2
2	2
-	2
carboxyethyl	2
)	2
phenethylamino	2
-	2
5	2
'	2
-	2
N	2
-	2
ethylcarboxamidoadenosine	2
(	0
CGS	1
21680	2
)	0
,	0
A2A	0
receptor	0
agonist	0
,	0
N6	1
-	2
cyclopentyladenosine	2
(	0
CPA	1
)	0
,	0
A1	0
receptor	0
agonist	0
,	0
and	0
5	1
'	2
-	2
N	2
-	2
ethylcarboxamidoadenosine	2
(	0
NECA	1
)	0
,	0
A2	0
/	0
A1	0
receptor	0
agonist	0
significantly	0
and	0
dose	0
-	0
dependently	0
decreased	0
cocaine	1
-	0
induced	0
locomotor	0
activity	0
.	0

CPA	1
reduced	0
cocaine	1
action	0
at	0
the	0
doses	0
which	0
,	0
given	0
alone	0
,	0
did	0
not	0
influence	0
motility	0
,	0
while	0
CGS	1
21680	2
and	0
NECA	1
decreased	0
the	0
action	0
of	0
cocaine	1
at	0
the	0
doses	0
which	0
,	0
given	0
alone	0
,	0
decreased	0
locomotor	0
activity	0
in	0
animals	0
.	0

These	0
results	0
suggest	0
the	0
involvement	0
of	0
both	0
adenosine	1
receptors	0
in	0
the	0
action	0
of	0
cocaine	1
although	0
agonists	0
of	0
A1	0
receptors	0
seem	0
to	0
have	0
stronger	0
influence	0
on	0
it	0
.	0

The	0
selective	0
blockade	0
of	0
A2	0
adenosine	1
receptor	0
by	0
DMPX	1
(	0
3	1
,	2
7	2
-	2
dimethyl	2
-	2
1	2
-	2
propargylxanthine	2
)	0
significantly	0
enhanced	0
cocaine	1
-	0
induced	0
locomotor	0
activity	0
of	0
animals	0
.	0

Caffeine	1
had	0
similar	0
action	0
but	0
the	0
effect	0
was	0
not	0
significant	0
.	0

CPT	1
(	0
8	1
-	2
cyclopentyltheophylline	2
)	0
-	0
-	0
A1	0
receptor	0
antagonist	0
,	0
did	0
not	0
show	0
any	0
influence	0
in	0
this	0
test	0
.	0

Similarly	0
,	0
all	0
adenosine	1
receptor	0
agonists	0
decreased	0
amphetamine	1
-	0
induced	0
hyperactivity	3
,	0
but	0
at	0
the	0
higher	0
doses	0
than	0
those	0
which	0
were	0
active	0
in	0
cocaine	1
-	0
induced	0
hyperactivity	3
.	0

The	0
selective	0
blockade	0
of	0
A2	0
adenosine	1
receptors	0
(	0
DMPX	1
)	0
and	0
non	0
-	0
selective	0
blockade	0
of	0
adenosine	1
receptors	0
(	0
caffeine	1
)	0
significantly	0
increased	0
the	0
action	0
of	0
amphetamine	1
in	0
the	0
locomotor	0
activity	0
test	0
.	0

0ur	0
results	0
have	0
shown	0
that	0
all	0
adenosine	1
receptor	0
agonists	0
(	0
A1	0
and	0
A2	0
)	0
reduce	0
cocaine	1
-	0
and	0
amphetamine	1
-	0
induced	0
locomotor	0
activity	0
and	0
indicate	0
that	0
cocaine	1
-	0
induced	0
hyperactivity	3
is	0
more	0
influenced	0
by	0
adenosine	1
receptor	0
agonists	0
(	0
particularly	0
A1	0
receptors	0
)	0
than	0
amphetamine	1
-	0
induced	0
hyperactivity	3
.	0

Amiodarone	1
and	0
the	0
risk	0
of	0
bradyarrhythmia	3
requiring	0
permanent	0
pacemaker	0
in	0
elderly	0
patients	0
with	0
atrial	3
fibrillation	4
and	0
prior	0
myocardial	3
infarction	4
.	0

0BJECTIVES	0
:	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
determine	0
whether	0
the	0
use	0
of	0
amiodarone	1
in	0
patients	0
with	0
atrial	3
fibrillation	4
(	0
AF	3
)	0
increases	0
the	0
risk	0
of	0
bradyarrhythmia	3
requiring	0
a	0
permanent	0
pacemaker	0
.	0

BACKGR0UND	0
:	0
Reports	0
of	0
severe	0
bradyarrhythmia	3
during	0
amiodarone	1
therapy	0
are	0
infrequent	0
and	0
limited	0
to	0
studies	0
assessing	0
the	0
therapy	0
'	0
s	0
use	0
in	0
the	0
management	0
of	0
patients	0
with	0
ventricular	3
arrhythmias	4
.	0

METH0DS	0
:	0
A	0
study	0
cohort	0
of	0
8	0
,	0
770	0
patients	0
age	0
>	0
or	0
=	0
65	0
years	0
with	0
a	0
new	0
diagnosis	0
of	0
AF	3
was	0
identified	0
from	0
a	0
provincewide	0
database	0
of	0
Quebec	0
residents	0
with	0
a	0
myocardial	3
infarction	4
(	0
MI	3
)	0
between	0
1991	0
and	0
1999	0
.	0

Using	0
a	0
nested	0
case	0
-	0
control	0
design	0
,	0
477	0
cases	0
of	0
bradyarrhythmia	3
requiring	0
a	0
permanent	0
pacemaker	0
were	0
matched	0
(	0
1	0
:	0
4	0
)	0
to	0
1	0
,	0
908	0
controls	0
.	0

Multivariable	0
logistic	0
regression	0
was	0
used	0
to	0
estimate	0
the	0
odds	0
ratio	0
(	0
0R	0
)	0
of	0
pacemaker	0
insertion	0
associated	0
with	0
amiodarone	1
use	0
,	0
controlling	0
for	0
baseline	0
risk	0
factors	0
and	0
exposure	0
to	0
sotalol	1
,	0
Class	0
I	0
antiarrhythmic	0
agents	0
,	0
beta	0
-	0
blockers	0
,	0
calcium	1
channel	0
blockers	0
,	0
and	0
digoxin	1
.	0

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

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

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

C0NCLUSI0NS	0
:	0
This	0
study	0
suggests	0
that	0
the	0
use	0
of	0
amiodarone	1
in	0
elderly	0
patients	0
with	0
AF	3
and	0
a	0
previous	0
MI	3
increases	0
the	0
risk	0
of	0
bradyarrhythmia	3
requiring	0
a	0
permanent	0
pacemaker	0
.	0

The	0
finding	0
of	0
an	0
augmented	0
risk	0
of	0
pacemaker	0
insertion	0
in	0
elderly	0
women	0
receiving	0
amiodarone	1
requires	0
further	0
investigation	0
.	0

Indomethacin	1
-	0
induced	0
morphologic	0
changes	0
in	0
the	0
rat	0
urinary	0
bladder	0
epithelium	0
.	0

0BJECTIVES	0
:	0
To	0
evaluate	0
the	0
morphologic	0
changes	0
in	0
rat	0
urothelium	0
induced	0
by	0
indomethacin	1
.	0

Nonsteroidal	0
anti	0
-	0
inflammatory	0
drug	0
-	0
induced	0
cystitis	3
is	0
a	0
poorly	0
recognized	0
and	0
under	0
-	0
reported	0
condition	0
.	0

In	0
addition	0
to	0
tiaprofenic	1
acid	2
,	0
indomethacin	1
has	0
been	0
reported	0
to	0
be	0
associated	0
with	0
this	0
condition	0
.	0

METH0DS	0
:	0
Three	0
groups	0
were	0
established	0
:	0
a	0
control	0
group	0
(	0
n	0
=	0
10	0
)	0
,	0
a	0
high	0
-	0
dose	0
group	0
(	0
n	0
=	0
10	0
)	0
,	0
treated	0
with	0
one	0
intraperitoneal	0
injection	0
of	0
indomethacin	1
20	0
mg	0
/	0
kg	0
,	0
and	0
a	0
therapeutic	0
dose	0
group	0
(	0
n	0
=	0
10	0
)	0
in	0
which	0
oral	0
indomethacin	1
was	0
administered	0
3	0
.	0
25	0
mg	0
/	0
kg	0
body	0
weight	0
daily	0
for	0
3	0
weeks	0
.	0

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

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

When	0
compared	0
with	0
the	0
control	0
group	0
,	0
both	0
indomethacin	1
groups	0
revealed	0
statistically	0
increased	0
numbers	0
of	0
mast	0
cells	0
in	0
the	0
mucosa	0
(	0
P	0
<	0
0	0
.	0
0001	0
)	0
and	0
penetration	0
of	0
lanthanum	1
nitrate	2
through	0
intercellular	0
areas	0
of	0
the	0
epithelium	0
.	0

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

C0NCLUSI0NS	0
:	0
Indomethacin	1
resulted	0
in	0
histopathologic	0
findings	0
typical	0
of	0
interstitial	3
cystitis	4
,	0
such	0
as	0
leaky	0
bladder	0
epithelium	0
and	0
mucosal	0
mastocytosis	3
.	0

The	0
true	0
incidence	0
of	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
drug	0
-	0
induced	0
cystitis	3
in	0
humans	0
must	0
be	0
clarified	0
by	0
prospective	0
clinical	0
trials	0
.	0

An	0
open	0
-	0
label	0
phase	0
II	0
study	0
of	0
low	0
-	0
dose	0
thalidomide	1
in	0
androgen	1
-	0
independent	0
prostate	3
cancer	4
.	0

The	0
antiangiogenic	0
effects	0
of	0
thalidomide	1
have	0
been	0
assessed	0
in	0
clinical	0
trials	0
in	0
patients	0
with	0
various	0
solid	0
and	0
haematological	3
malignancies	4
.	0

Thalidomide	1
blocks	0
the	0
activity	0
of	0
angiogenic	0
agents	0
including	0
bFGF	0
,	0
VEGF	0
and	0
IL	0
-	0
6	0
.	0

We	0
undertook	0
an	0
open	0
-	0
label	0
study	0
using	0
thalidomide	1
100	0
mg	0
once	0
daily	0
for	0
up	0
to	0
6	0
months	0
in	0
20	0
men	0
with	0
androgen	1
-	0
independent	0
prostate	3
cancer	4
.	0

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

Patients	0
underwent	0
regular	0
measurement	0
of	0
prostate	0
-	0
specific	0
antigen	0
(	0
PSA	0
)	0
,	0
urea	1
and	0
electrolytes	0
,	0
serum	0
bFGF	0
and	0
VEGF	0
.	0

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

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

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

Adverse	0
effects	0
included	0
constipation	3
,	0
morning	0
drowsiness	3
,	0
dizziness	3
and	0
rash	3
,	0
and	0
resulted	0
in	0
withdrawal	0
from	0
the	0
study	0
by	0
three	0
men	0
.	0

Evidence	0
of	0
peripheral	3
sensory	4
neuropathy	4
was	0
found	0
in	0
nine	0
of	0
13	0
men	0
before	0
treatment	0
.	0

In	0
the	0
seven	0
men	0
who	0
completed	0
six	0
months	0
on	0
thalidomide	1
,	0
subclinical	0
evidence	0
of	0
peripheral	3
neuropathy	4
was	0
found	0
in	0
four	0
before	0
treatment	0
,	0
but	0
in	0
all	0
seven	0
at	0
repeat	0
testing	0
.	0

The	0
findings	0
indicate	0
that	0
thalidomide	1
may	0
be	0
an	0
option	0
for	0
patients	0
who	0
have	0
failed	0
other	0
forms	0
of	0
therapy	0
,	0
provided	0
close	0
follow	0
-	0
up	0
is	0
maintained	0
for	0
development	0
of	0
peripheral	3
neuropathy	4
.	0

Central	3
nervous	4
system	4
toxicity	4
following	0
the	0
administration	0
of	0
levobupivacaine	1
for	0
lumbar	0
plexus	0
block	0
:	0
A	0
report	0
of	0
two	0
cases	0
.	0

BACKGR0UND	0
AND	0
0BJECTIVES	0
:	0
Central	3
nervous	4
system	4
and	4
cardiac	4
toxicity	4
following	0
the	0
administration	0
of	0
local	0
anesthetics	0
is	0
a	0
recognized	0
complication	0
of	0
regional	0
anesthesia	0
.	0

Levobupivacaine	1
,	0
the	0
pure	0
S	0
(	0
-	0
)	0
enantiomer	0
of	0
bupivacaine	1
,	0
was	0
developed	0
to	0
improve	0
the	0
cardiac	0
safety	0
profile	0
of	0
bupivacaine	1
.	0

We	0
describe	0
2	0
cases	0
of	0
grand	3
mal	4
seizures	4
following	0
accidental	0
intravascular	0
injection	0
of	0
levobupivacaine	1
.	0

CASE	0
REP0RT	0
:	0
Two	0
patients	0
presenting	0
for	0
elective	0
orthopedic	0
surgery	0
of	0
the	0
lower	0
limb	0
underwent	0
blockade	0
of	0
the	0
lumbar	0
plexus	0
via	0
the	0
posterior	0
approach	0
.	0

Immediately	0
after	0
the	0
administration	0
of	0
levobupivacaine	1
0	0
.	0
5	0
%	0
with	0
epinephrine	1
2	0
.	0
5	0
microgram	0
/	0
mL	0
,	0
the	0
patients	0
developed	0
grand	3
mal	4
seizures	4
,	0
despite	0
negative	0
aspiration	0
for	0
blood	0
and	0
no	0
clinical	0
signs	0
of	0
intravenous	0
epinephrine	1
administration	0
.	0

The	0
seizures	3
were	0
successfully	0
treated	0
with	0
sodium	1
thiopental	2
in	0
addition	0
to	0
succinylcholine	1
in	0
1	0
patient	0
.	0

Neither	0
patient	0
developed	0
signs	0
of	0
cardiovascular	3
toxicity	4
.	0

Both	0
patients	0
were	0
treated	0
preoperatively	0
with	0
beta	0
-	0
adrenergic	0
antagonist	0
medications	0
,	0
which	0
may	0
have	0
masked	0
the	0
cardiovascular	0
signs	0
of	0
the	0
unintentional	0
intravascular	0
administration	0
of	0
levobupivacaine	1
with	0
epinephrine	1
.	0

C0NCLUSI0NS	0
:	0
Although	0
levobupivacaine	1
may	0
have	0
a	0
safer	0
cardiac	3
toxicity	4
profile	0
than	0
racemic	0
bupivacaine	1
,	0
if	0
adequate	0
amounts	0
of	0
levobupivacaine	1
reach	0
the	0
circulation	0
,	0
it	0
will	0
result	0
in	0
convulsions	3
.	0

Plasma	0
concentrations	0
sufficient	0
to	0
result	0
in	0
central	3
nervous	4
system	4
toxicity	4
did	0
not	0
produce	0
manifestations	0
of	0
cardiac	3
toxicity	4
in	0
these	0
2	0
patients	0
.	0

Amiodarone	1
-	0
induced	0
torsade	3
de	4
pointes	4
during	0
bladder	0
irrigation	0
:	0
an	0
unusual	0
presentation	0
-	0
-	0
a	0
case	0
report	0
.	0

The	0
authors	0
present	0
a	0
case	0
of	0
early	0
(	0
within	0
4	0
days	0
)	0
development	0
of	0
torsade	3
de	4
pointes	4
(	0
TdP	3
)	0
associated	0
with	0
oral	0
amiodarone	1
therapy	0
.	0

Consistent	0
with	0
other	0
reports	0
this	0
case	0
of	0
TdP	3
occurred	0
in	0
the	0
context	0
of	0
multiple	0
exacerbating	0
factors	0
including	0
hypokalemia	3
and	0
digoxin	1
excess	0
.	0

Transient	0
prolongation	0
of	0
the	0
QT	0
during	0
bladder	0
irrigation	0
prompted	0
the	0
episode	0
of	0
TdP	3
.	0

It	0
is	0
well	0
known	0
that	0
bradycardia	3
exacerbates	0
acquired	0
TdP	3
.	0

The	0
authors	0
speculate	0
that	0
the	0
increased	0
vagal	0
tone	0
during	0
bladder	0
irrigation	0
,	0
a	0
vagal	0
maneuver	0
,	0
in	0
the	0
context	0
of	0
amiodarone	1
therapy	0
resulted	0
in	0
amiodarone	1
-	0
induced	0
proarrhythmia	3
.	0

In	0
the	0
absence	0
of	0
amiodarone	1
therapy	0
,	0
a	0
second	0
bladder	0
irrigation	0
did	0
not	0
induce	0
TdP	3
despite	0
hypokalemia	3
and	0
hypomagnesemia	3
.	0

Anaesthetic	0
complications	0
associated	0
with	0
myotonia	3
congenita	4
:	0
case	0
study	0
and	0
comparison	0
with	0
other	0
myotonic	3
disorders	4
.	0

Myotonia	3
congenita	4
(	0
MC	3
)	0
is	0
caused	0
by	0
a	0
defect	0
in	0
the	0
skeletal	0
muscle	0
chloride	1
channel	0
function	0
,	0
which	0
may	0
cause	0
sustained	3
membrane	4
depolarisation	4
.	0

We	0
describe	0
a	0
previously	0
healthy	0
32	0
-	0
year	0
-	0
old	0
woman	0
who	0
developed	0
a	0
life	0
-	0
threatening	0
muscle	3
spasm	4
and	0
secondary	0
ventilation	0
difficulties	0
following	0
a	0
preoperative	0
injection	0
of	0
suxamethonium	1
.	0

The	0
muscle	3
spasms	4
disappeared	0
spontaneously	0
and	0
the	0
surgery	0
proceeded	0
without	0
further	0
problems	0
.	0

When	0
subsequently	0
questioned	0
,	0
she	0
reported	0
minor	0
symptoms	0
suggesting	0
a	0
myotonic	3
condition	4
.	0

Myotonia	3
was	0
found	0
on	0
clinical	0
examination	0
and	0
EMG	0
.	0

The	0
diagnosis	0
MC	3
was	0
confirmed	0
genetically	0
.	0

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

We	0
give	0
a	0
brief	0
overview	0
of	0
ion	3
channel	4
disorders	4
including	0
malignant	3
hyperthermia	4
and	0
their	0
anaesthetic	0
considerations	0
.	0

Respiratory	0
pattern	0
in	0
a	0
rat	0
model	0
of	0
epilepsy	3
.	0

PURP0SE	0
:	0
Apnea	3
is	0
known	0
to	0
occur	0
during	0
seizures	3
,	0
but	0
systematic	0
studies	0
of	0
ictal	0
respiratory	0
changes	0
in	0
adults	0
are	0
few	0
.	0

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

Here	0
we	0
sought	0
to	0
generate	0
information	0
with	0
regard	0
to	0
the	0
interictal	0
period	0
in	0
animals	0
with	0
pilocarpine	1
-	0
induced	0
epilepsy	3
.	0

METH0DS	0
:	0
Twelve	0
rats	0
(	0
six	0
chronically	0
epileptic	3
animals	0
and	0
six	0
controls	0
)	0
were	0
anesthetized	0
,	0
given	0
tracheotomies	0
,	0
and	0
subjected	0
to	0
hyperventilation	3
or	0
hypoventilation	0
conditions	0
.	0

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

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

RESULTS	0
:	0
The	0
hyperventilation	3
maneuver	0
caused	0
a	0
decrease	0
in	0
spontaneous	0
ventilation	0
in	0
pilocarpine	1
-	0
treated	0
and	0
control	0
rats	0
.	0

Although	0
VE	0
had	0
a	0
similar	0
decrease	0
in	0
both	0
groups	0
,	0
in	0
the	0
epileptic	3
group	0
,	0
the	0
decrease	0
in	0
VE	0
was	0
due	0
to	0
a	0
significant	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
increase	0
in	0
TE	0
peak	0
in	0
relation	0
to	0
that	0
of	0
the	0
control	0
animals	0
.	0

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

In	0
the	0
epileptic	3
group	0
,	0
the	0
increase	0
in	0
VE	0
was	0
mediated	0
by	0
a	0
significant	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
decrease	0
in	0
TE	0
peak	0
compared	0
with	0
the	0
control	0
group	0
.	0

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

C0NCLUSI0NS	0
:	0
The	0
data	0
indicate	0
that	0
pilocarpine	1
-	0
treated	0
animals	0
have	0
an	0
altered	0
ability	0
to	0
react	0
to	0
(	0
or	0
compensate	0
for	0
)	0
blood	0
gas	0
changes	0
with	0
changes	0
in	0
ventilation	0
and	0
suggest	0
that	0
it	0
is	0
centrally	0
determined	0
.	0

We	0
speculate	0
on	0
the	0
possible	0
relation	0
of	0
the	0
current	0
findings	0
on	0
treating	0
different	0
epilepsy	3
-	0
associated	0
conditions	0
.	0

Fatal	0
myeloencephalopathy	3
due	0
to	0
intrathecal	0
vincristine	1
administration	0
.	0

Vincristine	1
was	0
accidentally	0
given	0
intrathecally	0
to	0
a	0
child	0
with	0
leukaemia	3
,	0
producing	0
sensory	3
and	4
motor	4
dysfunction	4
followed	0
by	0
encephalopathy	3
and	0
death	0
.	0

Separate	0
times	0
for	0
administering	0
vincristine	1
and	0
intrathecal	0
therapy	0
is	0
recommended	0
.	0

Progesterone	1
potentiation	0
of	0
bupivacaine	1
arrhythmogenicity	0
in	0
pentobarbital	1
-	0
anesthetized	0
rats	0
and	0
beating	0
rat	0
heart	0
cell	0
cultures	0
.	0

The	0
effects	0
of	0
progesterone	1
treatment	0
on	0
bupivacaine	1
arrhythmogenicity	0
in	0
beating	0
rat	0
heart	0
myocyte	0
cultures	0
and	0
on	0
anesthetized	0
rats	0
were	0
determined	0
.	0

After	0
determining	0
the	0
bupivacaine	1
AD50	0
(	0
the	0
concentration	0
of	0
bupivacaine	1
that	0
caused	0
50	0
%	0
of	0
all	0
beating	0
rat	0
heart	0
myocyte	0
cultures	0
to	0
become	0
arrhythmic	3
)	0
,	0
we	0
determined	0
the	0
effect	0
of	0
1	0
-	0
hour	0
progesterone	1
HCl	1
exposure	0
on	0
myocyte	0
contractile	0
rhythm	0
.	0

Each	0
concentration	0
of	0
progesterone	1
(	0
6	0
.	0
25	0
,	0
12	0
.	0
5	0
,	0
25	0
,	0
and	0
50	0
micrograms	0
/	0
ml	0
)	0
caused	0
a	0
significant	0
and	0
concentration	0
-	0
dependent	0
reduction	0
in	0
the	0
AD50	0
for	0
bupivacaine	1
.	0

Estradiol	1
treatment	0
also	0
increased	0
the	0
arrhythmogenicity	0
of	0
bupivacaine	1
in	0
myocyte	0
cultures	0
,	0
but	0
was	0
only	0
one	0
fourth	0
as	0
potent	0
as	0
progesterone	1
.	0

Neither	0
progesterone	1
nor	0
estradiol	1
effects	0
on	0
bupivacaine	1
arrhythmogenicity	0
were	0
potentiated	0
by	0
epinephrine	1
.	0

Chronic	0
progesterone	1
pretreatment	0
(	0
5	0
mg	0
/	0
kg	0
/	0
day	0
for	0
21	0
days	0
)	0
caused	0
a	0
significant	0
increase	0
in	0
bupivacaine	1
arrhythmogenicity	0
in	0
intact	0
pentobarbital	1
-	0
anesthetized	0
rats	0
.	0

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

The	0
results	0
of	0
this	0
study	0
indicate	0
that	0
progesterone	1
can	0
potentiate	0
bupivacaine	1
arrhythmogenicity	0
both	0
in	0
vivo	0
and	0
in	0
vitro	0
.	0

Potentiation	0
of	0
bupivacaine	1
arrhythmia	3
in	0
myocyte	0
cultures	0
suggests	0
that	0
this	0
effect	0
is	0
at	0
least	0
partly	0
mediated	0
at	0
the	0
myocyte	0
level	0
.	0

Increased	0
serum	0
soluble	0
Fas	0
in	0
patients	0
with	0
acute	3
liver	4
failure	4
due	0
to	0
paracetamol	1
overdose	3
.	0

BACKGR0UND	0
/	0
AIMS	0
:	0
Experimental	0
studies	0
have	0
suggested	0
that	0
apoptosis	0
via	0
the	0
Fas	0
/	0
Fas	0
Ligand	0
signaling	0
system	0
may	0
play	0
an	0
important	0
role	0
in	0
the	0
development	0
of	0
acute	3
liver	4
failure	4
.	0

The	0
aim	0
of	0
the	0
study	0
was	0
to	0
investigate	0
the	0
soluble	0
form	0
of	0
Fas	0
in	0
patients	0
with	0
acute	3
liver	4
failure	4
.	0

METH0D0L0GY	0
:	0
Serum	0
levels	0
of	0
sFas	0
(	0
soluble	0
Fas	0
)	0
were	0
measured	0
by	0
ELISA	0
in	0
24	0
patients	0
with	0
acute	3
liver	4
failure	4
and	0
10	0
normal	0
control	0
subjects	0
.	0

Serum	0
levels	0
of	0
tumor	3
necrosis	3
factor	0
-	0
alpha	0
and	0
interferon	0
-	0
gamma	0
were	0
also	0
determined	0
by	0
ELISA	0
.	0

RESULTS	0
:	0
Serum	0
sFas	0
was	0
significantly	0
increased	0
in	0
patients	0
with	0
acute	3
liver	4
failure	4
(	0
median	0
,	0
26	0
.	0
8	0
U	0
/	0
mL	0
;	0
range	0
,	0
6	0
.	0
9	0
-	0
52	0
.	0
7	0
U	0
/	0
mL	0
)	0
compared	0
to	0
the	0
normal	0
controls	0
(	0
median	0
,	0
8	0
.	0
6	0
U	0
/	0
mL	0
;	0
range	0
,	0
6	0
.	0
5	0
-	0
12	0
.	0
0	0
U	0
/	0
mL	0
,	0
P	0
<	0
0	0
.	0
0001	0
)	0
.	0

Levels	0
were	0
significantly	0
greater	0
in	0
patients	0
with	0
acute	3
liver	4
failure	4
due	0
to	0
paracetamol	1
overdose	3
(	0
median	0
,	0
28	0
.	0
7	0
U	0
/	0
mL	0
;	0
range	0
,	0
12	0
.	0
8	0
-	0
52	0
.	0
7	0
U	0
/	0
mL	0
,	0
n	0
=	0
17	0
)	0
than	0
those	0
due	0
to	0
non	0
-	0
A	0
to	0
E	0
hepatitis	3
(	0
median	0
,	0
12	0
.	0
5	0
U	0
/	0
mL	0
;	0
range	0
,	0
6	0
.	0
9	0
-	0
46	0
.	0
0	0
U	0
/	0
mL	0
,	0
n	0
=	0
7	0
,	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

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

A	0
significant	0
correlation	0
was	0
observed	0
between	0
serum	0
sFas	0
levels	0
and	0
aspartate	1
aminotransferase	0
(	0
r	0
=	0
0	0
.	0
613	0
,	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

C0NCLUSI0NS	0
:	0
The	0
increased	0
concentration	0
of	0
sFas	0
in	0
serum	0
of	0
patients	0
with	0
acute	3
liver	4
failure	4
may	0
reflect	0
activation	0
of	0
Fas	0
-	0
mediated	0
apoptosis	0
in	0
the	0
liver	0
and	0
this	0
together	0
with	0
increased	0
tumor	3
necrosis	3
factor	0
-	0
alpha	0
may	0
be	0
an	0
important	0
factor	0
in	0
liver	0
cell	0
loss	0
.	0

Bilateral	0
subthalamic	0
nucleus	0
stimulation	0
for	0
Parkinson	3
'	4
s	4
disease	4
.	0

High	0
frequency	0
stimulation	0
of	0
the	0
subthalamic	0
nucleus	0
(	0
STN	0
)	0
is	0
known	0
to	0
ameliorate	0
the	0
signs	0
and	0
symptoms	0
of	0
advanced	0
Parkinson	3
'	4
s	4
disease	4
.	0

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

METH0D	0
:	0
Twenty	0
-	0
three	0
patients	0
suffering	0
from	0
severe	0
Parkinson	3
'	4
s	4
disease	4
(	0
Stages	0
III	0
-	0
V	0
on	0
Hoehn	0
and	0
Yahr	0
scale	0
)	0
and	0
,	0
particularly	0
bradykinesia	3
,	0
rigidity	3
,	0
and	0
levodopa	1
-	0
induced	0
dyskinesias	3
underwent	0
bilateral	0
implantation	0
of	0
electrodes	0
in	0
the	0
STN	0
.	0

Preoperative	0
and	0
postoperative	0
assessments	0
of	0
these	0
patients	0
at	0
1	0
,	0
3	0
,	0
6	0
and	0
12	0
months	0
follow	0
-	0
up	0
,	0
in	0
"	0
on	0
"	0
and	0
"	0
off	0
"	0
drug	0
conditions	0
,	0
was	0
carried	0
out	0
using	0
Unified	0
Parkinson	3
'	4
s	4
Disease	4
Rating	0
Scale	0
,	0
Hoehn	0
and	0
Yahr	0
staging	0
,	0
England	0
activities	0
of	0
daily	0
living	0
score	0
and	0
video	0
recordings	0
.	0

RESULTS	0
:	0
After	0
one	0
year	0
of	0
electrical	0
stimulation	0
of	0
the	0
STN	0
,	0
the	0
patients	0
'	0
scores	0
for	0
activities	0
of	0
daily	0
living	0
and	0
motor	0
examination	0
scores	0
(	0
Unified	0
Parkinson	3
'	4
s	4
Disease	4
Rating	0
Scale	0
parts	0
II	0
and	0
III	0
)	0
off	0
medication	0
improved	0
by	0
62	0
%	0
and	0
61	0
%	0
respectively	0
(	0
p	0
<	0
0	0
.	0
0005	0
)	0
.	0

The	0
subscores	0
for	0
the	0
akinesia	3
,	0
rigidity	3
,	0
tremor	3
and	0
gait	0
also	0
improved	0
.	0

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

The	0
average	0
levodopa	1
dose	0
decreased	0
from	0
813	0
mg	0
to	0
359	0
mg	0
.	0

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

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

C0NCLUSI0N	0
:	0
Bilateral	0
subthalamic	0
nucleus	0
stimulation	0
is	0
an	0
effective	0
treatment	0
for	0
advanced	0
Parkinson	3
'	4
s	4
disease	4
.	0

It	0
reduces	0
the	0
severity	0
of	0
"	0
off	0
"	0
phase	0
symptoms	0
,	0
improves	0
the	0
axial	0
symptoms	0
and	0
reduces	0
levodopa	1
requirements	0
.	0

The	0
reduction	0
in	0
the	0
levodopa	1
dose	0
is	0
useful	0
in	0
controlling	0
drug	3
-	4
induced	4
dyskinesias	4
.	0

Acute	3
renal	4
failure	4
occurring	0
during	0
intravenous	0
desferrioxamine	1
therapy	0
:	0
recovery	0
after	0
haemodialysis	0
.	0

A	0
patient	0
with	0
transfusion	0
-	0
dependent	0
thalassemia	3
was	0
undergoing	0
home	0
intravenous	0
desferrioxamine	1
(	0
DFX	1
)	0
treatment	0
by	0
means	0
of	0
a	0
totally	0
implanted	0
system	0
because	0
of	0
his	0
poor	0
compliance	0
with	0
the	0
nightly	0
subcutaneous	0
therapy	0
.	0

Due	0
to	0
an	0
accidental	0
malfunctioning	0
of	0
the	0
infusion	0
pump	0
,	0
the	0
patient	0
was	0
inadvertently	0
administered	0
a	0
toxic	0
dosage	0
of	0
the	0
drug	0
which	0
caused	0
renal	3
insufficiency	4
.	0

Given	0
the	0
progressive	0
deterioration	0
of	0
the	0
symptoms	0
and	0
of	0
the	0
laboratory	0
values	0
,	0
despite	0
adequate	0
medical	0
treatment	0
,	0
a	0
decision	0
was	0
made	0
to	0
introduce	0
haemodialytical	0
therapy	0
in	0
order	0
to	0
remove	0
the	0
drug	0
and	0
therapy	0
reduce	0
the	0
nephrotoxicity	3
.	0

From	0
the	0
results	0
obtained	0
,	0
haemodialysis	0
can	0
therefore	0
be	0
suggested	0
as	0
a	0
useful	0
therapy	0
in	0
rare	0
cases	0
of	0
progressive	0
acute	3
renal	4
failure	4
caused	0
by	0
desferrioxamine	1
.	0

0cular	0
motility	0
changes	0
after	0
subtenon	0
carboplatin	1
chemotherapy	0
for	0
retinoblastoma	3
.	0

BACKGR0UND	0
:	0
Focal	0
subtenon	0
carboplatin	1
injections	0
have	0
recently	0
been	0
used	0
as	0
a	0
presumably	0
toxicity	3
-	0
free	0
adjunct	0
to	0
systemic	0
chemotherapy	0
for	0
intraocular	0
retinoblastoma	3
.	0

0BJECTIVE	0
:	0
To	0
report	0
our	0
clinical	0
experience	0
with	0
abnormal	3
ocular	4
motility	4
in	0
patients	0
treated	0
with	0
subtenon	0
carboplatin	1
chemotherapy	0
.	0

METH0DS	0
:	0
We	0
noted	0
abnormal	3
ocular	4
motility	4
in	0
10	0
consecutive	0
patients	0
with	0
retinoblastoma	3
who	0
had	0
received	0
subtenon	0
carboplatin	1
.	0

During	0
ocular	0
manipulation	0
under	0
general	0
anesthesia	0
,	0
we	0
assessed	0
their	0
eyes	0
by	0
forced	0
duction	0
testing	0
,	0
comparing	0
ocular	0
motility	0
after	0
tumor	3
control	0
with	0
ocular	0
motility	0
at	0
diagnosis	0
.	0

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

RESULTS	0
:	0
Limitation	0
of	0
ocular	0
motility	0
was	0
detected	0
in	0
all	0
12	0
eyes	0
of	0
10	0
patients	0
treated	0
for	0
intraocular	0
retinoblastoma	3
with	0
1	0
to	0
6	0
injections	0
of	0
subtenon	0
carboplatin	1
as	0
part	0
of	0
multimodality	0
therapy	0
.	0

Histopathological	0
examination	0
revealed	0
many	0
lipophages	0
in	0
the	0
periorbital	0
fat	0
surrounding	0
the	0
optic	0
nerve	0
in	0
1	0
eye	0
,	0
indicative	0
of	0
phagocytosis	0
of	0
previously	0
existing	0
fat	0
cells	0
and	0
suggesting	0
prior	0
fat	0
necrosis	3
.	0

The	0
enucleations	0
were	0
technically	0
difficult	0
and	0
hazardous	0
for	0
globe	0
rupture	3
because	0
of	0
extensive	0
orbital	0
soft	0
tissue	0
adhesions	0
.	0

C0NCLUSI0NS	0
:	0
Subtenon	0
carboplatin	1
chemotherapy	0
is	0
associated	0
with	0
significant	0
fibrosis	3
of	0
orbital	0
soft	0
tissues	0
,	0
leading	0
to	0
mechanical	0
restriction	0
of	0
eye	0
movements	0
and	0
making	0
subsequent	0
enucleation	0
difficult	0
.	0

Subtenon	0
carboplatin	1
is	0
not	0
free	0
of	0
toxicity	3
,	0
and	0
its	0
use	0
is	0
best	0
restricted	0
to	0
specific	0
indications	0
.	0

Ethambutol	1
and	0
optic	3
neuropathy	4
.	0

PURP0SE	0
:	0
To	0
demonstrate	0
the	0
association	0
between	0
ethambutol	1
and	0
optic	3
neuropathy	4
.	0

METH0D	0
:	0
Thirteen	0
patients	0
who	0
developed	0
optic	3
neuropathy	4
after	0
being	0
treated	0
with	0
ethambutol	1
for	0
tuberculosis	3
of	4
the	4
lung	4
or	4
lymph	4
node	4
at	0
Siriraj	0
Hospital	0
between	0
1997	0
and	0
2001	0
were	0
retrospectively	0
reviewed	0
.	0

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

RESULTS	0
:	0
All	0
patients	0
had	0
optic	3
neuropathy	4
between	0
1	0
to	0
6	0
months	0
(	0
mean	0
=	0
2	0
.	0
9	0
months	0
)	0
after	0
starting	0
ethambutol	1
therapy	0
at	0
a	0
dosage	0
ranging	0
from	0
13	0
to	0
20	0
mg	0
/	0
kg	0
/	0
day	0
(	0
mean	0
=	0
17	0
mg	0
/	0
kg	0
/	0
day	0
)	0
.	0

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

0f	0
6	0
patients	0
with	0
irreversible	0
visual	3
impairment	4
,	0
4	0
patients	0
had	0
diabetes	3
mellitus	4
,	0
glaucoma	3
and	0
a	0
history	0
of	0
heavy	0
smoking	0
.	0

C0NCLUSI0N	0
:	0
Early	0
recognition	0
of	0
optic	3
neuropathy	4
should	0
be	0
considered	0
in	0
patients	0
with	0
ethambutol	1
therapy	0
.	0

A	0
low	0
dose	0
and	0
prompt	0
discontinuation	0
of	0
the	0
drug	0
is	0
recommended	0
particularly	0
in	0
individuals	0
with	0
diabetes	3
mellitus	4
,	0
glaucoma	3
or	0
who	0
are	0
heavy	0
smokers	0
.	0

Treatment	0
of	0
compensatory	0
gustatory	3
hyperhidrosis	4
with	0
topical	0
glycopyrrolate	1
.	0

Gustatory	3
hyperhidrosis	4
is	0
facial	0
sweating	3
usually	0
associated	0
with	0
the	0
eating	0
of	0
hot	0
spicy	0
food	0
or	0
even	0
smelling	0
this	0
food	0
.	0

Current	0
options	0
of	0
treatment	0
include	0
oral	0
anticholinergic	0
drugs	0
,	0
the	0
topical	0
application	0
of	0
anticholinergics	0
or	0
aluminum	1
chloride	2
,	0
and	0
the	0
injection	0
of	0
botulinum	0
toxin	0
.	0

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

All	0
patients	0
had	0
gustatory	3
hyperhidrosis	4
,	0
which	0
interfered	0
with	0
their	0
social	0
activities	0
,	0
after	0
transthroacic	0
endoscopic	0
sympathectomy	0
,	0
and	0
which	0
was	0
associated	0
with	0
compensatory	0
focal	0
hyperhidrosis	3
.	0

After	0
applying	0
topical	0
glycopyrrolate	1
,	0
the	0
subjective	0
effect	0
was	0
excellent	0
(	0
no	0
sweating	3
after	0
eating	0
hot	0
spicy	0
food	0
)	0
in	0
10	0
patients	0
(	0
77	0
%	0
)	0
,	0
and	0
fair	0
(	0
clearly	0
reduced	0
sweating	3
)	0
in	0
3	0
patients	0
(	0
23	0
%	0
)	0
.	0

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

Adverse	0
effects	0
included	0
a	0
mildly	0
dry	3
mouth	4
and	0
a	0
sore	3
throat	4
in	0
2	0
patients	0
(	0
2	0
%	0
glycopyrrolate	1
)	0
,	0
a	0
light	0
headache	3
in	0
1	0
patient	0
(	0
1	0
.	0
5	0
%	0
glycopyrrolate	1
)	0
.	0

The	0
topical	0
application	0
of	0
a	0
glycopyrrolate	1
pad	0
appeared	0
to	0
be	0
safe	0
,	0
efficacious	0
,	0
well	0
tolerated	0
,	0
and	0
a	0
convenient	0
method	0
of	0
treatment	0
for	0
moderate	0
to	0
severe	0
symptoms	0
of	0
gustatory	3
hyperhidrosis	4
in	0
post	0
transthoracic	0
endoscopic	0
sympathectomy	0
or	0
sympathicotomy	0
patients	0
,	0
with	0
few	0
side	0
effects	0
.	0

Neuroleptic	1
-	0
associated	0
hyperprolactinemia	3
.	0

Can	0
it	0
be	0
treated	0
with	0
bromocriptine	1
?	0

Six	0
stable	0
psychiatric	0
outpatients	0
with	0
hyperprolactinemia	3
and	0
amenorrhea	3
/	0
oligomenorrhea	3
associated	0
with	0
their	0
neuroleptic	1
medications	2
were	0
treated	0
with	0
bromocriptine	1
.	0

Daily	0
dosages	0
of	0
5	0
-	0
10	0
mg	0
corrected	0
the	0
hyperprolactinemia	3
and	0
restored	0
menstruation	0
in	0
four	0
of	0
the	0
six	0
patients	0
.	0

0ne	0
woman	0
,	0
however	0
,	0
developed	0
worsened	0
psychiatric	3
symptoms	4
while	0
taking	0
bromocriptine	1
,	0
and	0
it	0
was	0
discontinued	0
.	0

Thus	0
,	0
three	0
of	0
six	0
patients	0
had	0
their	0
menstrual	0
irregularity	0
successfully	0
corrected	0
with	0
bromocriptine	1
.	0

This	0
suggests	0
that	0
bromocriptine	1
should	0
be	0
further	0
evaluated	0
as	0
potential	0
therapy	0
for	0
neuroleptic	1
-	0
associated	0
hyperprolactinemia	3
and	0
amenorrhea	3
/	0
galactorrhea	3
.	0

Ethacrynic	1
acid	2
-	0
induced	0
convulsions	3
and	0
brain	0
neurotransmitters	0
in	0
mice	0
.	0

Intracerebroventricular	0
injection	0
of	0
ethacrynic	1
acid	2
(	0
50	0
%	0
convulsive	3
dose	0
;	0
50	0
micrograms	0
/	0
mouse	0
)	0
accelerated	0
the	0
synthesis	0
/	0
turnover	0
of	0
5	1
-	2
hydroxytryptamine	2
(	0
5	1
-	2
HT	2
)	0
but	0
suppressed	0
the	0
synthesis	0
of	0
gamma	1
-	2
aminobutyric	2
acid	2
and	0
acetylcholine	1
in	0
mouse	0
brain	0
.	0

These	0
effects	0
were	0
completely	0
antagonized	0
by	0
pretreatment	0
with	0
a	0
glutamate	1
/	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
antagonist	0
,	0
aminophosphonovaleric	1
acid	2
.	0

In	0
ethacrynic	1
acid	2
-	0
induced	0
convulsions	3
,	0
these	0
neurotransmitter	0
systems	0
may	0
be	0
differentially	0
modulated	0
,	0
probably	0
through	0
activation	0
of	0
glutaminergic	0
neurons	0
in	0
the	0
brain	0
.	0

Pharmacology	0
of	0
gamma	1
-	2
aminobutyric	2
acidA	2
receptor	0
complex	0
after	0
the	0
in	0
vivo	0
administration	0
of	0
the	0
anxioselective	0
and	0
anticonvulsant	0
beta	1
-	2
carboline	2
derivative	0
abecarnil	1
.	0

In	0
rodents	0
,	0
the	0
effect	0
of	0
the	0
beta	1
-	2
carboline	2
derivative	0
isopropyl	1
-	2
6	2
-	2
benzyloxy	2
-	2
4	2
-	2
methoxymethyl	2
-	2
beta	2
-	2
carboline	2
-	2
3	2
-	2
carboxylate	2
(	0
abecarrnil	1
)	0
,	0
a	0
new	0
ligand	0
for	0
benzodiazepine	1
receptors	0
possessing	0
anxiolytic	0
and	0
anticonvulsant	0
properties	0
,	0
was	0
evaluated	0
on	0
the	0
function	0
of	0
central	0
gamma	1
-	2
aminobutyric	2
acid	2
(	0
GABA	1
)	0
A	0
receptor	0
complex	0
,	0
both	0
in	0
vitro	0
and	0
in	0
vivo	0
.	0

Added	0
in	0
vitro	0
to	0
rat	0
cortical	0
membrane	0
preparation	0
,	0
abecarnil	1
increased	0
[	0
3H	0
]	0
GABA	1
binding	0
,	0
enhanced	0
muscimol	1
-	0
stimulated	0
36Cl	0
-	0
uptake	0
and	0
reduced	0
the	0
binding	0
of	0
t	1
-	2
[	2
35S	2
]	2
butylbicyclophosphorothionate	2
(	0
[	1
35S	2
]	2
TBPS	2
)	0
.	0

These	0
effects	0
were	0
similar	0
to	0
those	0
induced	0
by	0
diazepam	1
,	0
whereas	0
the	0
partial	0
agonist	0
Ro	1
16	2
-	2
6028	2
(	0
tert	1
-	2
butyl	2
-	2
(	2
S	2
)	2
-	2
8	2
-	2
bromo	2
-	2
11	2
,	2
12	2
,	2
13	2
,	2
13a	2
-	2
tetrahydro	2
-	2
9	2
-	2
oxo	2
-	2
9H	2
-	2
imidazo	2
[	2
1	2
,	2
5	2
-	2
a	2
]	2
-	2
pyrrolo	2
-	2
[	2
2	2
,	2
1	2
-	2
c	2
]	2
[	2
1	2
,	2
4	2
]	2
benzodiazepine	2
-	2
1	2
-	2
carboxylate	2
)	0
showed	0
very	0
weak	0
efficacy	0
in	0
these	0
biochemical	0
tests	0
.	0

After	0
i	0
.	0
p	0
.	0
injection	0
to	0
rats	0
,	0
abecarnil	1
and	0
diazepam	1
decreased	0
in	0
a	0
time	0
-	0
dependent	0
and	0
dose	0
-	0
related	0
(	0
0	0
.	0
25	0
-	0
20	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
manner	0
[	1
35S	2
]	2
TBPS	2
binding	0
measured	0
ex	0
vivo	0
in	0
the	0
cerebral	0
cortex	0
.	0

Moreover	0
,	0
both	0
drugs	0
at	0
the	0
dose	0
of	0
0	0
.	0
5	0
mg	0
/	0
kg	0
antagonized	0
completely	0
the	0
convulsant	0
activity	0
and	0
the	0
increase	0
of	0
[	1
35S	2
]	2
TBPS	2
binding	0
induced	0
by	0
isoniazide	1
(	0
350	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
as	0
well	0
as	0
the	0
increase	0
of	0
[	1
35S	2
]	2
TBPS	2
binding	0
induced	0
by	0
foot	0
-	0
shock	0
stress	0
.	0

To	0
better	0
correlate	0
the	0
biochemical	0
and	0
the	0
pharmacological	0
effects	0
,	0
we	0
studied	0
the	0
action	0
of	0
abecarnil	1
on	0
[	1
35S	2
]	2
TBPS	2
binding	0
,	0
exploratory	0
motility	0
and	0
on	0
isoniazid	1
-	0
induced	0
biochemical	0
and	0
pharmacological	0
effects	0
in	0
mice	0
.	0

In	0
these	0
animals	0
,	0
abecarnil	1
produced	0
a	0
paralleled	0
dose	0
-	0
dependent	0
(	0
0	0
.	0
05	0
-	0
1	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
reduction	0
of	0
both	0
motor	0
behavior	0
and	0
cortical	0
[	0
35S	0
]	0
TBPS	0
binding	0
.	0

Moreover	0
,	0
0	0
.	0
05	0
mg	0
/	0
kg	0
of	0
this	0
beta	1
-	2
carboline	2
reduced	0
markedly	0
the	0
increase	0
of	0
[	1
35S	2
]	2
TBPS	2
binding	0
and	0
the	0
convulsions	3
induced	0
by	0
isoniazid	1
(	0
200	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Recurrent	0
myocardial	3
infarction	4
in	0
a	0
postpartum	0
patient	0
receiving	0
bromocriptine	1
.	0

Myocardial	3
infarction	4
in	0
puerperium	0
is	0
infrequently	0
reported	0
.	0

Spasm	3
,	0
coronary	0
dissection	0
,	0
or	0
atheromatous	0
etiology	0
has	0
been	0
described	0
.	0

Bromocriptine	1
has	0
been	0
implicated	0
in	0
several	0
previous	0
case	0
reports	0
of	0
myocardial	3
infarction	4
in	0
the	0
puerperium	0
.	0

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

Although	0
generally	0
regarded	0
as	0
"	0
safe	0
,	0
"	0
possible	0
serious	0
cardiac	0
effects	0
of	0
bromocriptine	1
should	0
be	0
acknowledged	0
.	0

Asterixis	3
induced	0
by	0
carbamazepine	1
therapy	0
.	0

There	0
are	0
very	0
few	0
reports	0
about	0
asterixis	3
as	0
a	0
side	0
effect	0
of	0
treatment	0
with	0
psychopharmacologic	0
agents	0
.	0

In	0
this	0
report	0
we	0
present	0
four	0
patients	0
treated	0
with	0
a	0
combination	0
of	0
different	0
psychotropic	0
drugs	0
,	0
in	0
whom	0
asterixis	3
was	0
triggered	0
either	0
by	0
adding	0
carbamazepine	1
(	0
CBZ	1
)	0
to	0
a	0
treatment	0
regimen	0
,	0
or	0
by	0
increasing	0
its	0
dosage	0
.	0

Neither	0
dosage	0
nor	0
serum	0
levels	0
of	0
CBZ	1
were	0
in	0
a	0
higher	0
range	0
.	0

We	0
consider	0
asterixis	3
to	0
be	0
an	0
easily	0
overlooked	0
sign	0
of	0
neurotoxicity	3
,	0
which	0
may	0
occur	0
even	0
at	0
low	0
or	0
moderate	0
dosage	0
levels	0
,	0
if	0
certain	0
drugs	0
as	0
lithium	1
or	0
clozapine	1
are	0
used	0
in	0
combination	0
with	0
CBZ	1
.	0

Pharmacodynamics	0
of	0
the	0
hypotensive	3
effect	0
of	0
levodopa	1
in	0
parkinsonian	3
patients	0
.	0

Blood	0
pressure	0
effects	0
of	0
i	0
.	0
v	0
.	0
levodopa	1
were	0
examined	0
in	0
parkinsonian	3
patients	0
with	0
stable	0
and	0
fluctuating	0
responses	0
to	0
levodopa	1
.	0

The	0
magnitude	0
of	0
the	0
hypotensive	3
effect	0
of	0
levodopa	1
was	0
concentration	0
dependent	0
and	0
was	0
fit	0
to	0
an	0
Emax	0
model	0
in	0
fluctuating	0
responders	0
.	0

Stable	0
responders	0
demonstrated	0
a	0
small	0
hypotensive	3
response	0
.	0

Baseline	0
blood	0
pressures	0
were	0
higher	0
in	0
fluctuating	0
patients	0
;	0
a	0
higher	0
baseline	0
blood	0
pressure	0
correlated	0
with	0
greater	0
hypotensive	3
effects	0
.	0

Antiparkinsonian	0
effects	0
of	0
levodopa	1
temporally	0
correlated	0
with	0
blood	0
pressure	0
changes	0
.	0

Phenylalanine	1
,	0
a	0
large	0
neutral	0
amino	1
acid	2
(	0
LNAA	0
)	0
competing	0
with	0
levodopa	1
for	0
transport	0
across	0
the	0
blood	0
-	0
brain	0
barrier	0
,	0
reduced	0
the	0
hypotensive	3
and	0
antiparkinsonian	0
effects	0
of	0
levodopa	1
.	0

We	0
conclude	0
that	0
levodopa	1
has	0
a	0
central	0
hypotensive	3
action	0
that	0
parallels	0
the	0
motor	0
effects	0
in	0
fluctuating	0
patients	0
.	0

The	0
hypotensive	3
effect	0
appears	0
to	0
be	0
related	0
to	0
the	0
higher	0
baseline	0
blood	0
pressure	0
we	0
observed	0
in	0
fluctuating	0
patients	0
relative	0
to	0
stable	0
patients	0
.	0

Syndrome	3
of	4
inappropriate	4
secretion	4
of	4
antidiuretic	4
hormone	4
after	0
infusional	0
vincristine	1
.	0

A	0
77	0
-	0
year	0
-	0
old	0
woman	0
with	0
refractory	0
multiple	3
myeloma	4
was	0
treated	0
with	0
a	0
4	0
-	0
day	0
continuous	0
intravenous	0
infusion	0
of	0
vincristine	1
and	0
doxorubicin	1
and	0
4	0
days	0
of	0
oral	0
dexamethasone	1
.	0

Nine	0
days	0
after	0
her	0
second	0
cycle	0
she	0
presented	0
with	0
lethargy	3
and	0
weakness	3
associated	0
with	0
hyponatremia	3
.	0

Evaluation	0
revealed	0
the	0
syndrome	3
of	4
inappropriate	4
secretion	4
of	4
antidiuretic	4
hormone	4
,	0
which	0
was	0
attributed	0
to	0
the	0
vincristine	1
infusion	0
.	0

After	0
normal	0
serum	0
sodium	1
levels	0
returned	0
,	0
further	0
doxorubicin	1
and	0
dexamethasone	1
chemotherapy	0
without	0
vincristine	1
did	0
not	0
produce	0
this	0
complication	0
.	0

Heart	3
failure	4
:	0
to	0
digitalise	0
or	0
not	0
?	0

The	0
view	0
against	0
.	0

Despite	0
extensive	0
clinical	0
experience	0
the	0
role	0
of	0
digoxin	1
is	0
still	0
not	0
well	0
defined	0
.	0

In	0
patients	0
with	0
atrial	3
fibrillation	4
digoxin	1
is	0
beneficial	0
for	0
ventricular	0
rate	0
control	0
.	0

For	0
patients	0
in	0
sinus	0
rhythm	0
and	0
heart	3
failure	4
the	0
situation	0
is	0
less	0
clear	0
.	0

Digoxin	1
has	0
a	0
narrow	0
therapeutic	0
:	0
toxic	0
ratio	0
and	0
concentrations	0
are	0
affected	0
by	0
a	0
number	0
of	0
drugs	0
.	0

Also	0
,	0
digoxin	1
has	0
undesirable	0
effects	0
such	0
as	0
increasing	0
peripheral	0
resistance	0
and	0
myocardial	0
demands	0
,	0
and	0
causing	0
arrhythmias	3
.	0

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

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

More	0
convincing	0
evidence	0
is	0
required	0
showing	0
that	0
digoxin	1
improves	0
symptoms	0
or	0
exercise	0
capacity	0
.	0

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

Pooled	0
analysis	0
of	0
the	0
effects	0
of	0
other	0
inotropic	0
drugs	0
shows	0
an	0
excess	0
mortality	0
and	0
there	0
is	0
a	0
possibility	0
that	0
digoxin	1
may	0
increase	0
mortality	0
after	0
myocardial	3
infarction	4
(	0
MI	3
)	0
.	0

Angiotensin	1
-	0
converting	0
enzyme	0
(	0
ACE	0
)	0
inhibitors	0
should	0
be	0
used	0
first	0
as	0
they	0
are	0
safer	0
,	0
do	0
not	0
require	0
blood	0
level	0
monitoring	0
,	0
modify	0
progression	0
of	0
disease	0
,	0
relieve	0
symptoms	0
,	0
improve	0
exercise	0
tolerance	0
and	0
reduce	0
mortality	0
.	0

Caution	0
should	0
be	0
exercised	0
in	0
using	0
digoxin	1
until	0
large	0
mortality	0
trials	0
are	0
completed	0
showing	0
either	0
benefit	0
or	0
harm	0
.	0

Until	0
then	0
digoxin	1
should	0
be	0
considered	0
a	0
third	0
-	0
line	0
therapy	0
.	0

Isradipine	1
treatment	0
for	0
hypertension	3
in	0
general	0
practice	0
in	0
Hong	0
Kong	0
.	0

A	0
6	0
-	0
week	0
open	0
study	0
of	0
the	0
introduction	0
of	0
isradipine	1
treatment	0
was	0
conducted	0
in	0
general	0
practice	0
in	0
Hong	0
Kong	0
.	0

303	0
Chinese	0
patients	0
with	0
mild	0
to	0
moderate	0
hypertension	3
entered	0
the	0
study	0
.	0

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

The	0
main	0
side	0
-	0
effects	0
were	0
headache	3
,	0
dizziness	3
,	0
palpitation	3
and	0
flushing	3
and	0
these	0
were	0
not	0
more	0
frequent	0
than	0
reported	0
in	0
other	0
studies	0
with	0
isradipine	1
or	0
with	0
placebo	0
.	0

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

Similar	0
reductions	0
occurred	0
in	0
standing	0
blood	0
pressure	0
and	0
there	0
was	0
no	0
evidence	0
of	0
postural	3
hypotension	4
.	0

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

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

Pharmacological	0
characteristics	0
and	0
side	0
effects	0
of	0
a	0
new	0
galenic	0
formulation	0
of	0
propofol	1
without	0
soyabean	0
oil	0
.	0

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

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

Plasma	0
propofol	1
levels	0
were	0
measured	0
for	0
48	0
h	0
following	0
drug	0
administration	0
and	0
evaluated	0
according	0
to	0
a	0
three	0
-	0
compartment	0
model	0
.	0

The	0
pharmacodynamic	0
parameters	0
assessed	0
included	0
induction	0
and	0
emergence	0
times	0
,	0
respiratory	0
and	0
cardiovascular	0
effects	0
,	0
and	0
pain	3
on	0
injection	0
.	0

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

0wing	0
to	0
a	0
high	0
incidence	0
of	0
thrombophlebitis	3
,	0
the	0
study	0
was	0
terminated	0
prematurely	0
and	0
only	0
the	0
data	0
of	0
the	0
two	0
parallel	0
treatment	0
groups	0
(	0
15	0
patients	0
in	0
each	0
group	0
)	0
were	0
analysed	0
.	0

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

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

Pain	3
on	0
injection	0
(	0
80	0
vs	0
.	0
20	0
%	0
,	0
p	0
<	0
0	0
.	0
01	0
)	0
and	0
thrombophlebitis	3
(	0
93	0
.	0
3	0
vs	0
.	0
6	0
.	0
6	0
%	0
,	0
p	0
<	0
0	0
.	0
001	0
)	0
occurred	0
more	0
frequently	0
with	0
AM149	0
than	0
with	0
Disoprivan	1
.	0

Although	0
both	0
formulations	0
had	0
similar	0
pharmacokinetic	0
and	0
pharmacodynamic	0
profiles	0
the	0
new	0
formulation	0
is	0
not	0
suitable	0
for	0
clinical	0
use	0
due	0
to	0
the	0
high	0
incidence	0
of	0
thrombophlebitis	3
produced	0
.	0

Pure	3
red	4
cell	4
aplasia	4
,	0
toxic	3
dermatitis	4
and	0
lymphadenopathy	3
in	0
a	0
patient	0
taking	0
diphenylhydantoin	1
.	0

A	0
patient	0
taking	0
diphenylhydantoin	1
for	0
3	0
weeks	0
developed	0
a	0
generalized	0
skin	3
rash	4
,	0
lymphadenopathy	3
and	0
pure	3
red	4
cell	4
aplasia	4
.	0

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

Skin	3
rash	4
is	0
a	0
well	0
-	0
known	0
complication	0
of	0
diphenylhydantoin	1
treatment	0
as	0
is	0
benign	0
and	0
malignant	0
lymphadenopathy	3
.	0

Pure	3
red	4
cell	4
aplasia	4
associated	0
with	0
diphenylhydantoin	1
medication	0
has	0
been	0
reported	0
in	0
3	0
patients	0
.	0

The	0
exact	0
mechanism	0
by	0
which	0
diphenylhydantoin	1
exerts	0
its	0
toxic	0
effects	0
is	0
not	0
known	0
.	0

In	0
this	0
patient	0
the	0
time	0
relation	0
between	0
the	0
ingestion	0
of	0
diphenylhydantoin	1
and	0
the	0
occurrence	0
of	0
the	0
skin	3
rash	4
,	0
lymphadenopathy	3
and	0
pure	3
red	4
cell	4
aplasia	4
is	0
very	0
suggestive	0
of	0
a	0
direct	0
connection	0
.	0

Vinorelbine	1
-	0
related	0
cardiac	0
events	0
:	0
a	0
meta	0
-	0
analysis	0
of	0
randomized	0
clinical	0
trials	0
.	0

Several	0
cases	0
of	0
cardiac	0
adverse	0
reactions	0
related	0
to	0
vinorelbine	1
(	0
VNR	1
)	0
have	0
been	0
reported	0
in	0
the	0
literature	0
.	0

In	0
order	0
to	0
quantify	0
the	0
incidence	0
of	0
these	0
cardiac	0
events	0
,	0
we	0
performed	0
a	0
meta	0
-	0
analysis	0
of	0
clinical	0
trials	0
comparing	0
VNR	1
with	0
other	0
chemotherapeutic	0
agents	0
in	0
the	0
treatment	0
of	0
various	0
malignancies	3
.	0

Randomized	0
clinical	0
trials	0
comparing	0
VNR	1
with	0
other	0
drugs	0
in	0
the	0
treatment	0
of	0
cancer	3
were	0
searched	0
in	0
Medline	0
,	0
Embase	0
,	0
Evidence	0
-	0
based	0
Medicine	0
Reviews	0
databases	0
and	0
the	0
Cochrane	0
library	0
from	0
1987	0
to	0
2002	0
.	0

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

We	0
found	0
19	0
trials	0
,	0
involving	0
2441	0
patients	0
treated	0
by	0
VNR	1
and	0
2050	0
control	0
patients	0
.	0

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

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

The	0
risk	0
of	0
VNR	1
cardiac	0
events	0
was	0
similar	0
to	0
vindesine	1
(	0
VDS	1
)	0
and	0
other	0
cardiotoxic	3
drugs	0
[	0
fluorouracil	1
,	0
anthracyclines	1
,	0
gemcitabine	1
(	0
GEM	1
)	0
em	0
leader	0
]	0
.	0

Even	0
if	0
it	0
did	0
not	0
reach	0
statistical	0
significance	0
because	0
of	0
a	0
few	0
number	0
of	0
cases	0
,	0
the	0
risk	0
was	0
lower	0
in	0
trials	0
excluding	0
patients	0
with	0
cardiac	0
history	0
,	0
and	0
seemed	0
to	0
be	0
higher	0
in	0
trials	0
including	0
patients	0
with	0
pre	0
-	0
existing	0
cardiac	3
diseases	4
.	0

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

However	0
,	0
the	0
risk	0
associated	0
with	0
VNR	1
seems	0
to	0
be	0
similar	0
to	0
that	0
of	0
other	0
chemotherapeutic	0
agents	0
in	0
the	0
same	0
indications	0
.	0

MRI	0
findings	0
of	0
hypoxic	0
cortical	0
laminar	0
necrosis	3
in	0
a	0
child	0
with	0
hemolytic	3
anemia	4
crisis	0
.	0

We	0
present	0
magnetic	0
resonance	0
imaging	0
findings	0
of	0
a	0
5	0
-	0
year	0
-	0
old	0
girl	0
who	0
had	0
a	0
rapidly	0
installing	0
hemolytic	3
anemia	4
crisis	0
induced	0
by	0
trimethoprim	1
-	2
sulfomethoxazole	2
,	0
resulting	0
in	0
cerebral	3
anoxia	4
leading	0
to	0
permanent	0
damage	0
.	0

Magnetic	0
Resonance	0
imaging	0
revealed	0
cortical	0
laminar	0
necrosis	3
in	0
arterial	0
border	0
zones	0
in	0
both	0
cerebral	0
hemispheres	0
,	0
ischemic	0
changes	0
in	0
subcortical	0
white	0
matter	0
of	0
left	0
cerebral	0
hemisphere	0
,	0
and	0
in	0
the	0
left	0
putamen	0
.	0

Although	0
cortical	0
laminar	0
necrosis	3
is	0
a	0
classic	0
entity	0
in	0
adulthood	0
related	0
to	0
conditions	0
of	0
energy	0
depletions	0
,	0
there	0
are	0
few	0
reports	0
available	0
in	0
children	0
.	0

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

The	0
natural	0
history	0
of	0
Vigabatrin	1
associated	0
visual	3
field	4
defects	4
in	0
patients	0
electing	0
to	0
continue	0
their	0
medication	0
.	0

PURP0SE	0
:	0
To	0
determine	0
the	0
natural	0
history	0
of	0
visual	3
field	4
defects	4
in	0
a	0
group	0
of	0
patients	0
known	0
to	0
have	0
Vigabatrin	1
-	0
associated	0
changes	0
who	0
elected	0
to	0
continue	0
the	0
medication	0
because	0
of	0
good	0
seizure	3
control	0
.	0

METH0DS	0
:	0
All	0
patients	0
taking	0
Vigabatrin	1
alone	0
or	0
in	0
combination	0
with	0
other	0
antiepileptic	0
drugs	0
for	0
at	0
least	0
5	0
years	0
(	0
range	0
5	0
-	0
12	0
years	0
)	0
were	0
entered	0
into	0
a	0
visual	0
surveillance	0
programme	0
.	0

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

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

Following	0
already	0
published	0
methodology	0
(	0
Eye	0
2002	0
;	0
16	0
;	0
567	0
-	0
571	0
)	0
monocular	0
mean	0
radial	0
degrees	0
(	0
MRDs	0
)	0
to	0
the	0
I	0
/	0
4e	0
isopter	0
on	0
Goldmann	0
perimetry	0
was	0
calculated	0
for	0
the	0
right	0
eye	0
at	0
the	0
time	0
of	0
discovery	0
of	0
a	0
visual	3
field	4
defect	4
and	0
again	0
after	0
not	0
less	0
than	0
18	0
months	0
follow	0
-	0
up	0
.	0

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

0nly	0
one	0
patient	0
demonstrated	0
a	0
deterioration	3
in	4
visual	4
field	4
during	0
the	0
study	0
period	0
and	0
discontinued	0
treatment	0
.	0

C0NCLUSI0N	0
:	0
Established	0
visual	3
field	4
defects	4
presumed	0
to	0
be	0
due	0
to	0
Vigabatrin	1
therapy	0
did	0
not	0
usually	0
progress	0
in	0
spite	0
of	0
continuing	0
use	0
of	0
the	0
medication	0
.	0

These	0
data	0
give	0
support	0
to	0
the	0
hypothesis	0
that	0
the	0
pathogenesis	0
of	0
Vigabatrin	1
-	0
associated	0
visual	3
field	4
defects	4
may	0
be	0
an	0
idiosyncratic	0
adverse	0
drug	0
reaction	0
rather	0
than	0
dose	0
-	0
dependent	0
toxicity	3
.	0

Induction	0
of	0
rosaceiform	0
dermatitis	3
during	0
treatment	0
of	0
facial	3
inflammatory	4
dermatoses	4
with	0
tacrolimus	1
ointment	0
.	0

BACKGR0UND	0
:	0
Tacrolimus	1
ointment	0
is	0
increasingly	0
used	0
for	0
anti	0
-	0
inflammatory	0
treatment	0
of	0
sensitive	0
areas	0
such	0
as	0
the	0
face	0
,	0
and	0
recent	0
observations	0
indicate	0
that	0
the	0
treatment	0
is	0
effective	0
in	0
steroid	1
-	0
aggravated	0
rosacea	3
and	0
perioral	3
dermatitis	4
.	0

We	0
report	0
on	0
rosaceiform	0
dermatitis	3
as	0
a	0
complication	0
of	0
treatment	0
with	0
tacrolimus	1
ointment	0
.	0

0BSERVATI0NS	0
:	0
Six	0
adult	0
patients	0
with	0
inflammatory	3
facial	4
dermatoses	4
were	0
treated	0
with	0
tacrolimus	1
ointment	0
because	0
of	0
the	0
ineffectiveness	0
of	0
standard	0
treatments	0
.	0

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

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

In	0
1	0
patient	0
with	0
eyelid	0
eczema	3
,	0
rosaceiform	0
periocular	3
dermatitis	4
gradually	0
appeared	0
after	0
3	0
weeks	0
of	0
treatment	0
.	0

In	0
1	0
patient	0
with	0
atopic	3
dermatitis	4
,	0
telangiectatic	0
and	0
papular	3
rosacea	4
insidiously	0
appeared	0
after	0
5	0
months	0
of	0
treatment	0
.	0

C0NCLUSI0NS	0
:	0
0ur	0
observations	0
suggest	0
that	0
the	0
spectrum	0
of	0
rosaceiform	0
dermatitis	3
as	0
a	0
complication	0
of	0
treatment	0
with	0
tacrolimus	1
ointment	0
is	0
heterogeneous	0
.	0

A	0
variety	0
of	0
factors	0
,	0
such	0
as	0
vasoactive	0
properties	0
of	0
tacrolimus	1
,	0
proliferation	0
of	0
Demodex	0
due	0
to	0
local	0
immunosuppression	0
,	0
and	0
the	0
occlusive	0
properties	0
of	0
the	0
ointment	0
,	0
may	0
be	0
involved	0
in	0
the	0
observed	0
phenomena	0
.	0

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

Intravascular	0
hemolysis	3
and	0
acute	3
renal	4
failure	4
following	0
intermittent	0
rifampin	1
therapy	0
.	0

Renal	3
failure	4
is	0
a	0
rare	0
complication	0
associated	0
with	0
the	0
use	0
of	0
rifampin	1
.	0

Intravascular	0
hemolysis	3
leading	0
to	0
acute	3
renal	4
failure	4
following	0
rifampin	1
therapy	0
is	0
extremely	0
rare	0
.	0

Two	0
patients	0
with	0
leprosy	3
who	0
developed	0
hemolysis	3
and	0
acute	3
renal	4
failure	4
following	0
rifampin	1
are	0
reported	0
.	0

Structural	0
abnormalities	0
in	0
the	0
brains	0
of	0
human	0
subjects	0
who	0
use	0
methamphetamine	1
.	0

We	0
visualize	0
,	0
for	0
the	0
first	0
time	0
,	0
the	0
profile	0
of	0
structural	3
deficits	4
in	4
the	4
human	4
brain	4
associated	0
with	0
chronic	0
methamphetamine	1
(	0
MA	1
)	0
abuse	0
.	0

Studies	0
of	0
human	0
subjects	0
who	0
have	0
used	0
MA	1
chronically	0
have	0
revealed	0
deficits	0
in	0
dopaminergic	0
and	0
serotonergic	0
systems	0
and	0
cerebral	0
metabolic	3
abnormalities	4
.	0

Using	0
magnetic	0
resonance	0
imaging	0
(	0
MRI	0
)	0
and	0
new	0
computational	0
brain	0
-	0
mapping	0
techniques	0
,	0
we	0
determined	0
the	0
pattern	0
of	0
structural	0
brain	0
alterations	0
associated	0
with	0
chronic	0
MA	1
abuse	0
in	0
human	0
subjects	0
and	0
related	0
these	0
deficits	0
to	0
cognitive	3
impairment	4
.	0

We	0
used	0
high	0
-	0
resolution	0
MRI	0
and	0
surface	0
-	0
based	0
computational	0
image	0
analyses	0
to	0
map	0
regional	0
abnormalities	3
in	4
the	4
cortex	4
,	4
hippocampus	4
,	4
white	4
matter	4
,	4
and	4
ventricles	4
in	0
22	0
human	0
subjects	0
who	0
used	0
MA	1
and	0
21	0
age	0
-	0
matched	0
,	0
healthy	0
controls	0
.	0

Cortical	0
maps	0
revealed	0
severe	0
gray	0
-	0
matter	0
deficits	0
in	0
the	0
cingulate	0
,	0
limbic	0
,	0
and	0
paralimbic	0
cortices	0
of	0
MA	1
abusers	0
(	0
averaging	0
11	0
.	0
3	0
%	0
below	0
control	0
;	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

0n	0
average	0
,	0
MA	1
abusers	0
had	0
7	0
.	0
8	0
%	0
smaller	0
hippocampal	0
volumes	0
than	0
control	0
subjects	0
(	0
p	0
<	0
0	0
.	0
01	0
;	0
left	0
,	0
p	0
=	0
0	0
.	0
01	0
;	0
right	0
,	0
p	0
<	0
0	0
.	0
05	0
)	0
and	0
significant	0
white	0
-	0
matter	0
hypertrophy	3
(	0
7	0
.	0
0	0
%	0
;	0
p	0
<	0
0	0
.	0
01	0
)	0
.	0

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

MRI	0
-	0
based	0
maps	0
suggest	0
that	0
chronic	0
methamphetamine	1
abuse	0
causes	0
a	0
selective	0
pattern	0
of	0
cerebral	0
deterioration	0
that	0
contributes	0
to	0
impaired	3
memory	4
performance	4
.	0

MA	1
may	0
selectively	0
damage	0
the	0
medial	0
temporal	0
lobe	0
and	0
,	0
consistent	0
with	0
metabolic	0
studies	0
,	0
the	0
cingulate	0
-	0
limbic	0
cortex	0
,	0
inducing	0
neuroadaptation	0
,	0
neuropil	0
reduction	0
,	0
or	0
cell	0
death	0
.	0

Prominent	0
white	0
-	0
matter	0
hypertrophy	3
may	0
result	0
from	0
altered	0
myelination	0
and	0
adaptive	0
glial	0
changes	0
,	0
including	0
gliosis	3
secondary	0
to	0
neuronal	3
damage	4
.	0

These	0
brain	0
substrates	0
may	0
help	0
account	0
for	0
the	0
symptoms	0
of	0
MA	1
abuse	0
,	0
providing	0
therapeutic	0
targets	0
for	0
drug	0
-	0
induced	0
brain	3
injury	4
.	0

Disruption	0
of	0
hepatic	0
lipid	0
homeostasis	0
in	0
mice	0
after	0
amiodarone	1
treatment	0
is	0
associated	0
with	0
peroxisome	0
proliferator	0
-	0
activated	0
receptor	0
-	0
alpha	0
target	0
gene	0
activation	0
.	0

Amiodarone	1
,	0
an	0
efficacious	0
and	0
widely	0
used	0
antiarrhythmic	0
agent	0
,	0
has	0
been	0
reported	0
to	0
cause	0
hepatotoxicity	3
in	0
some	0
patients	0
.	0

To	0
gain	0
insight	0
into	0
the	0
mechanism	0
of	0
this	0
unwanted	0
effect	0
,	0
mice	0
were	0
administered	0
various	0
doses	0
of	0
amiodarone	1
and	0
examined	0
for	0
changes	0
in	0
hepatic	0
histology	0
and	0
gene	0
regulation	0
.	0

Amiodarone	1
induced	0
hepatomegaly	3
,	0
hepatocyte	0
microvesicular	0
lipid	0
accumulation	0
,	0
and	0
a	0
significant	0
decrease	0
in	0
serum	0
triglycerides	1
and	0
glucose	1
.	0

Northern	0
blot	0
analysis	0
of	0
hepatic	0
RNA	0
revealed	0
a	0
dose	0
-	0
dependent	0
increase	0
in	0
the	0
expression	0
of	0
a	0
number	0
of	0
genes	0
critical	0
for	0
fatty	1
acid	2
oxidation	0
,	0
lipoprotein	0
assembly	0
,	0
and	0
lipid	0
transport	0
.	0

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

The	0
absence	0
of	0
induction	0
of	0
these	0
genes	0
as	0
well	0
as	0
hepatomegaly	3
in	0
PPARalpha	0
knockout	0
[	0
PPARalpha	0
-	0
/	0
-	0
]	0
mice	0
indicated	0
that	0
the	0
effects	0
of	0
amiodarone	1
were	0
dependent	0
upon	0
the	0
presence	0
of	0
a	0
functional	0
PPARalpha	0
gene	0
.	0

Compared	0
to	0
wild	0
-	0
type	0
mice	0
,	0
treatment	0
of	0
PPARalpha	0
-	0
/	0
-	0
mice	0
with	0
amiodarone	1
resulted	0
in	0
an	0
increased	0
rate	0
and	0
extent	0
of	0
total	0
body	0
weight	3
loss	4
.	0

The	0
inability	0
of	0
amiodarone	1
to	0
directly	0
activate	0
either	0
human	0
or	0
mouse	0
PPARalpha	0
transiently	0
expressed	0
in	0
human	0
HepG2	0
hepatoma	3
cells	0
indicates	0
that	0
the	0
effects	0
of	0
amiodarone	1
on	0
the	0
function	0
of	0
this	0
receptor	0
were	0
indirect	0
.	0

Based	0
upon	0
these	0
results	0
,	0
we	0
conclude	0
that	0
amiodarone	1
disrupts	0
hepatic	0
lipid	0
homeostasis	0
and	0
that	0
the	0
increased	0
expression	0
of	0
PPARalpha	0
target	0
genes	0
is	0
secondary	0
to	0
this	0
toxic	0
effect	0
.	0

These	0
results	0
provide	0
important	0
new	0
mechanistic	0
information	0
regarding	0
the	0
hepatotoxic	3
effects	0
of	0
amiodarone	1
and	0
indicate	0
that	0
PPARalpha	0
protects	0
against	0
amiodarone	1
-	0
induced	0
hepatotoxicity	3
.	0

Safety	0
and	0
compliance	0
with	0
once	0
-	0
daily	0
niacin	1
extended	2
-	2
release	2
/	2
lovastatin	2
as	0
initial	0
therapy	0
in	0
the	0
Impact	0
of	0
Medical	0
Subspecialty	0
on	0
Patient	0
Compliance	0
to	0
Treatment	0
(	0
IMPACT	0
)	0
study	0
.	0

Niacin	1
extended	2
-	2
release	2
/	2
lovastatin	2
is	0
a	0
new	0
combination	0
product	0
approved	0
for	0
treatment	0
of	0
primary	0
hypercholesterolemia	3
and	0
mixed	0
dyslipidemia	3
.	0

This	0
open	0
-	0
labeled	0
,	0
multicenter	0
study	0
evaluated	0
the	0
safety	0
of	0
bedtime	0
niacin	1
extended	2
-	2
release	2
/	2
lovastatin	2
when	0
dosed	0
as	0
initial	0
therapy	0
and	0
patient	0
compliance	0
to	0
treatment	0
in	0
various	0
clinical	0
practice	0
settings	0
.	0

A	0
total	0
of	0
4	0
,	0
499	0
patients	0
with	0
dyslipidemia	3
requiring	0
drug	0
intervention	0
was	0
enrolled	0
at	0
1	0
,	0
081	0
sites	0
.	0

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

Patients	0
also	0
received	0
dietary	0
counseling	0
,	0
educational	0
materials	0
,	0
and	0
reminders	0
to	0
call	0
a	0
toll	0
-	0
free	0
number	0
that	0
provided	0
further	0
education	0
about	0
dyslipidemia	3
and	0
niacin	1
extended	2
-	2
release	2
/	2
lovastatin	2
.	0

Primary	0
end	0
points	0
were	0
study	0
compliance	0
,	0
increases	0
in	0
liver	0
transaminases	0
to	0
>	0
3	0
times	0
the	0
upper	0
limit	0
of	0
normal	0
,	0
and	0
clinical	0
myopathy	3
.	0

Final	0
study	0
status	0
was	0
available	0
for	0
4	0
,	0
217	0
patients	0
(	0
94	0
%	0
)	0
.	0

Compliance	0
to	0
niacin	1
extended	2
-	2
release	2
/	2
lovastatin	2
was	0
77	0
%	0
,	0
with	0
3	0
,	0
245	0
patients	0
completing	0
the	0
study	0
.	0

Patients	0
in	0
the	0
southeast	0
and	0
those	0
enrolled	0
by	0
endocrinologists	0
had	0
the	0
lowest	0
compliance	0
and	0
highest	0
adverse	0
event	0
rates	0
.	0

Flushing	3
was	0
the	0
most	0
common	0
adverse	0
event	0
,	0
reported	0
by	0
18	0
%	0
of	0
patients	0
and	0
leading	0
to	0
discontinuation	0
by	0
6	0
%	0
.	0

Incidence	0
of	0
increased	0
aspartate	1
aminotransferase	0
and	0
/	0
or	0
alanine	1
aminotransferase	0
>	0
3	0
times	0
the	0
upper	0
limit	0
of	0
normal	0
was	0
<	0
0	0
.	0
3	0
%	0
.	0

An	0
increase	0
of	0
creatine	1
phosphokinase	0
to	0
>	0
5	0
times	0
the	0
upper	0
limit	0
of	0
normal	0
occurred	0
in	0
0	0
.	0
24	0
%	0
of	0
patients	0
,	0
and	0
no	0
cases	0
of	0
drug	0
-	0
induced	0
myopathy	3
were	0
observed	0
.	0

Niacin	1
extended	2
-	2
release	2
/	2
lovastatin	2
1	0
,	0
000	0
/	0
40	0
mg	0
,	0
dosed	0
as	0
initial	0
therapy	0
,	0
was	0
associated	0
with	0
good	0
compliance	0
and	0
safety	0
and	0
had	0
very	0
low	0
incidences	0
of	0
increased	0
liver	0
and	0
muscle	0
enzymes	0
.	0

Protective	0
effect	0
of	0
Terminalia	1
chebula	2
against	0
experimental	0
myocardial	3
injury	4
induced	0
by	0
isoproterenol	1
.	0

Cardioprotective	0
effect	0
of	0
ethanolic	1
extract	2
of	2
Terminalia	2
chebula	2
fruits	2
(	0
500	0
mg	0
/	0
kg	0
body	0
wt	0
)	0
was	0
examined	0
in	0
isoproterenol	1
(	0
200	0
mg	0
/	0
kg	0
body	0
wt	0
)	0
induced	0
myocardial	3
damage	4
in	0
rats	0
.	0

In	0
isoproterenol	1
administered	0
rats	0
,	0
the	0
level	0
of	0
lipid	0
peroxides	1
increased	0
significantly	0
in	0
the	0
serum	0
and	0
heart	0
.	0

A	0
significant	0
decrease	0
was	0
observed	0
in	0
the	0
activity	0
of	0
the	0
myocardial	0
marker	0
enzymes	0
with	0
a	0
concomitant	0
increase	0
in	0
their	0
activity	0
in	0
serum	0
.	0

Histopathological	0
examination	0
was	0
carried	0
out	0
to	0
confirm	0
the	0
myocardial	0
necrosis	3
.	0

T	1
.	2
chebula	2
extract	2
pretreatment	0
was	0
found	0
to	0
ameliorate	0
the	0
effect	0
of	0
isoproterenol	1
on	0
lipid	0
peroxide	1
formation	0
and	0
retained	0
the	0
activities	0
of	0
the	0
diagnostic	0
marker	0
enzymes	0
.	0

A	0
case	0
of	0
postoperative	0
anxiety	3
due	0
to	0
low	0
dose	0
droperidol	1
used	0
with	0
patient	0
-	0
controlled	0
analgesia	0
.	0

A	0
multiparous	0
woman	0
in	0
good	0
psychological	0
health	0
underwent	0
urgent	0
caesarean	0
section	0
in	0
labour	0
.	0

Postoperatively	0
,	0
she	0
was	0
given	0
a	0
patient	0
-	0
controlled	0
analgesia	0
device	0
delivering	0
boluses	0
of	0
diamorphine	1
0	0
.	0
5	0
mg	0
and	0
droperidol	1
0	0
.	0
025	0
mg	0
.	0

Whilst	0
using	0
the	0
device	0
she	0
gradually	0
became	0
anxious	0
,	0
the	0
feeling	0
worsening	0
after	0
each	0
bolus	0
.	0

The	0
diagnosis	0
of	0
droperidol	1
-	0
induced	0
psychological	3
disturbance	4
was	0
not	0
made	0
straight	0
away	0
although	0
on	0
subsequent	0
close	0
questioning	0
the	0
patient	0
gave	0
a	0
very	0
clear	0
history	0
.	0

After	0
she	0
had	0
received	0
a	0
total	0
of	0
only	0
0	0
.	0
9	0
mg	0
droperidol	1
,	0
a	0
syringe	0
containing	0
diamorphine	1
only	0
was	0
substituted	0
and	0
her	0
unease	0
resolved	0
completely	0
.	0

We	0
feel	0
that	0
,	0
although	0
the	0
dramatic	0
extrapyramidal	0
side	0
effects	0
of	0
dopaminergic	0
antiemetics	0
are	0
well	0
known	0
,	0
more	0
subtle	0
manifestations	0
may	0
easily	0
be	0
overlooked	0
.	0

Accurate	0
patient	0
history	0
contributes	0
to	0
differentiating	0
diabetes	3
insipidus	4
:	0
a	0
case	0
study	0
.	0

This	0
case	0
study	0
highlights	0
the	0
important	0
contribution	0
of	0
nursing	0
in	0
obtaining	0
an	0
accurate	0
health	0
history	0
.	0

The	0
case	0
discussed	0
herein	0
initially	0
appeared	0
to	0
be	0
neurogenic	3
diabetes	4
insipidus	4
(	0
DI	3
)	0
secondary	0
to	0
a	0
traumatic	3
brain	4
injury	4
.	0

The	0
nursing	0
staff	0
,	0
by	0
reviewing	0
the	0
patient	0
'	0
s	0
health	0
history	0
with	0
his	0
family	0
,	0
discovered	0
a	0
history	0
of	0
polydipsia	3
and	0
long	0
-	0
standing	0
lithium	1
use	0
.	0

Lithium	1
is	0
implicated	0
in	0
drug	0
-	0
induced	0
nephrogenic	3
DI	4
,	0
and	0
because	0
the	0
patient	0
had	0
not	0
received	0
lithium	1
since	0
being	0
admitted	0
to	0
the	0
hospital	0
,	0
his	0
treatment	0
changed	0
to	0
focus	0
on	0
nephrogenic	3
DI	4
.	0

By	0
combining	0
information	0
from	0
the	0
patient	0
history	0
,	0
the	0
physical	0
examination	0
,	0
and	0
radiologic	0
and	0
laboratory	0
studies	0
,	0
the	0
critical	0
care	0
team	0
demonstrated	0
that	0
the	0
patient	0
had	0
been	0
self	0
-	0
treating	0
his	0
lithium	1
-	0
induced	0
nephrogenic	3
DI	4
and	0
developed	0
neurogenic	3
DI	4
secondary	0
to	0
brain	3
trauma	4
.	0

Thus	0
successful	0
treatment	0
required	0
that	0
nephrogenic	0
and	0
neurogenic	3
DI	4
be	0
treated	0
concomitantly	0
.	0

Factors	0
contributing	0
to	0
ribavirin	1
-	0
induced	0
anemia	3
.	0

BACKGR0UND	0
AND	0
AIM	0
:	0
Interferon	1
and	0
ribavirin	1
combination	0
therapy	0
for	0
chronic	3
hepatitis	4
C	4
produces	0
hemolytic	3
anemia	4
.	0

This	0
study	0
was	0
conducted	0
to	0
identify	0
the	0
factors	0
contributing	0
to	0
ribavirin	1
-	0
induced	0
anemia	3
.	0

METH0DS	0
:	0
Eighty	0
-	0
eight	0
patients	0
with	0
chronic	3
hepatitis	4
C	4
who	0
received	0
interferon	1
-	2
alpha	2
-	2
2b	2
at	0
a	0
dose	0
of	0
6	0
MU	0
administered	0
intramuscularly	0
for	0
24	0
weeks	0
in	0
combination	0
with	0
ribavirin	1
administered	0
orally	0
at	0
a	0
dose	0
of	0
600	0
mg	0
or	0
800	0
mg	0
participated	0
in	0
the	0
study	0
.	0

A	0
hemoglobin	0
concentration	0
of	0
<	0
10	0
g	0
/	0
dL	0
was	0
defined	0
as	0
ribavirin	1
-	0
induced	0
anemia	3
.	0

RESULTS	0
:	0
Ribavirin	1
-	0
induced	0
anemia	3
occurred	0
in	0
18	0
(	0
20	0
.	0
5	0
%	0
)	0
patients	0
during	0
treatment	0
.	0

A	0
2	0
g	0
/	0
dL	0
decrease	0
in	0
hemoglobin	0
concentrations	0
in	0
patients	0
with	0
anemia	3
was	0
observed	0
at	0
week	0
2	0
after	0
the	0
start	0
of	0
treatment	0
.	0

The	0
hemoglobin	0
concentration	0
in	0
patients	0
with	0
>	0
or	0
=	0
2	0
g	0
/	0
dL	0
decrease	0
at	0
week	0
2	0
was	0
observed	0
to	0
be	0
significantly	0
lower	0
even	0
after	0
week	0
2	0
than	0
in	0
patients	0
with	0
<	0
2	0
g	0
/	0
dL	0
decrease	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

A	0
significant	0
relationship	0
was	0
observed	0
between	0
the	0
rate	0
of	0
reduction	0
of	0
hemoglobin	0
concentrations	0
at	0
week	0
2	0
and	0
the	0
severity	0
of	0
anemia	3
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

Such	0
factors	0
as	0
sex	0
(	0
female	0
)	0
,	0
age	0
(	0
>	0
or	0
=	0
60	0
years	0
old	0
)	0
,	0
and	0
the	0
ribavirin	1
dose	0
by	0
body	0
weight	0
(	0
12	0
mg	0
/	0
kg	0
or	0
more	0
)	0
were	0
significant	0
by	0
univariate	0
analysis	0
.	0

C0NCLUSI0NS	0
:	0
Careful	0
administration	0
is	0
necessary	0
in	0
patients	0
>	0
or	0
=	0
60	0
years	0
old	0
,	0
in	0
female	0
patients	0
,	0
and	0
in	0
patients	0
receiving	0
a	0
ribavirin	1
dose	0
of	0
12	0
mg	0
/	0
kg	0
or	0
more	0
.	0

Patients	0
who	0
experience	0
a	0
fall	0
in	0
hemoglobin	0
concentrations	0
of	0
2	0
g	0
/	0
dL	0
or	0
more	0
at	0
week	0
2	0
after	0
the	0
start	0
of	0
treatment	0
should	0
be	0
monitored	0
with	0
particular	0
care	0
.	0

Zidovudine	1
-	0
induced	0
hepatitis	3
.	0

A	0
case	0
of	0
acute	0
hepatitis	3
induced	0
by	0
zidovudine	1
in	0
a	0
38	0
-	0
year	0
-	0
old	0
patient	0
with	0
AIDS	3
is	0
presented	0
.	0

The	0
mechanism	0
whereby	0
the	0
hepatitis	3
was	0
induced	0
is	0
not	0
known	0
.	0

However	0
,	0
the	0
patient	0
tolerated	0
well	0
an	0
alternative	0
reverse	0
transcriptase	0
inhibitor	0
,	0
2	1
'	2
3	2
'	2
dideoxyinosine	2
.	0

Physicians	0
caring	0
for	0
patients	0
with	0
AIDS	3
should	0
be	0
aware	0
of	0
this	0
hitherto	0
rarely	0
reported	0
complication	0
.	0

0xidative	0
damage	0
precedes	0
nitrative	0
damage	0
in	0
adriamycin	1
-	0
induced	0
cardiac	0
mitochondrial	3
injury	4
.	0

The	0
purpose	0
of	0
the	0
present	0
study	0
was	0
to	0
determine	0
if	0
elevated	0
reactive	0
oxygen	1
(	0
R0S	0
)	0
/	0
nitrogen	1
species	0
(	0
RNS	0
)	0
reported	0
to	0
be	0
present	0
in	0
adriamycin	1
(	0
ADR	1
)	0
-	0
induced	0
cardiotoxicity	3
actually	0
resulted	0
in	0
cardiomyocyte	0
oxidative	0
/	0
nitrative	0
damage	0
,	0
and	0
to	0
quantitatively	0
determine	0
the	0
time	0
course	0
and	0
subcellular	0
localization	0
of	0
these	0
postulated	0
damage	0
products	0
using	0
an	0
in	0
vivo	0
approach	0
.	0

B6C3	0
mice	0
were	0
treated	0
with	0
a	0
single	0
dose	0
of	0
20	0
mg	0
/	0
kg	0
ADR	1
.	0

Ultrastructural	0
damage	0
and	0
levels	0
of	0
4	1
-	2
hydroxy	2
-	2
2	2
-	2
nonenal	2
(	0
4HNE	1
)	0
-	0
protein	0
adducts	0
and	0
3	1
-	2
nitrotyrosine	2
(	0
3NT	1
)	0
were	0
analyzed	0
.	0

Quantitative	0
ultrastructural	0
damage	0
using	0
computerized	0
image	0
techniques	0
showed	0
cardiomyocyte	0
injury	0
as	0
early	0
as	0
3	0
hours	0
,	0
with	0
mitochondria	0
being	0
the	0
most	0
extensively	0
and	0
progressively	0
injured	0
subcellular	0
organelle	0
.	0

Analysis	0
of	0
4HNE	1
protein	0
adducts	0
by	0
immunogold	0
electron	0
microscopy	0
showed	0
appearance	0
of	0
4HNE	1
protein	0
adducts	0
in	0
mitochondria	0
as	0
early	0
as	0
3	0
hours	0
,	0
with	0
a	0
peak	0
at	0
6	0
hours	0
and	0
subsequent	0
decline	0
at	0
24	0
hours	0
.	0

3NT	1
levels	0
were	0
significantly	0
increased	0
in	0
all	0
subcellular	0
compartments	0
at	0
6	0
hours	0
and	0
subsequently	0
declined	0
at	0
24	0
hours	0
.	0

0ur	0
data	0
showed	0
ADR	1
induced	0
4HNE	1
-	0
protein	0
adducts	0
in	0
mitochondria	0
at	0
the	0
same	0
time	0
point	0
as	0
when	0
mitochondrial	3
injury	4
initially	0
appeared	0
.	0

These	0
results	0
document	0
for	0
the	0
first	0
time	0
in	0
vivo	0
that	0
mitochondrial	3
oxidative	4
damage	4
precedes	0
nitrative	0
damage	0
.	0

The	0
progressive	0
nature	0
of	0
mitochondrial	3
injury	4
suggests	0
that	0
mitochondria	0
,	0
not	0
other	0
subcellular	0
organelles	0
,	0
are	0
the	0
major	0
site	0
of	0
intracellular	0
injury	0
.	0

Sotalol	1
-	0
induced	0
coronary	3
spasm	4
in	0
a	0
patient	0
with	0
dilated	3
cardiomyopathy	4
associated	0
with	0
sustained	0
ventricular	3
tachycardia	4
.	0

A	0
54	0
-	0
year	0
-	0
old	0
man	0
with	0
severe	0
left	0
ventricular	3
dysfunction	4
due	0
to	0
dilated	3
cardiomyopathy	4
was	0
referred	0
to	0
our	0
hospital	0
for	0
symptomatic	0
incessant	0
sustained	0
ventricular	3
tachycardia	4
(	0
VT	3
)	0
.	0

After	0
the	0
administration	0
of	0
nifekalant	1
hydrochloride	2
,	0
sustained	0
VT	3
was	0
terminated	0
.	0

An	0
alternate	0
class	0
III	0
agent	0
,	0
sotalol	1
,	0
was	0
also	0
effective	0
for	0
the	0
prevention	0
of	0
VT	3
.	0

However	0
,	0
one	0
month	0
after	0
switching	0
over	0
nifekalant	1
to	0
sotalol	1
,	0
a	0
short	0
duration	0
of	0
ST	0
elevation	0
was	0
documented	0
in	0
ECG	0
monitoring	0
at	0
almost	0
the	0
same	0
time	0
for	0
three	0
consecutive	0
days	0
.	0

ST	0
elevation	0
with	0
chest	0
discomfort	0
disappeared	0
since	0
he	0
began	0
taking	0
long	0
-	0
acting	0
diltiazem	1
.	0

Coronary	3
vasospasm	4
may	0
be	0
induced	0
by	0
the	0
non	0
-	0
selective	0
beta	0
-	0
blocking	0
properties	0
of	0
sotalol	1
.	0

Effects	0
of	0
the	0
antidepressant	0
trazodone	1
,	0
a	0
5	1
-	2
HT	2
2A	0
/	0
2C	0
receptor	0
antagonist	0
,	0
on	0
dopamine	1
-	0
dependent	0
behaviors	0
in	0
rats	0
.	0

RATI0NALE	0
:	0
5	1
-	2
Hydroxytryptamine	2
,	0
via	0
stimulation	0
of	0
5	1
-	2
HT	2
2C	0
receptors	0
,	0
exerts	0
a	0
tonic	0
inhibitory	0
influence	0
on	0
dopaminergic	0
neurotransmission	0
,	0
whereas	0
activation	0
of	0
5	1
-	2
HT	2
2A	0
receptors	0
enhances	0
stimulated	0
DAergic	0
neurotransmission	0
.	0

The	0
antidepressant	0
trazodone	1
is	0
a	0
5	1
-	2
HT	2
2A	0
/	0
2C	0
receptor	0
antagonist	0
.	0

0BJECTIVES	0
:	0
To	0
evaluate	0
the	0
effect	0
of	0
trazodone	1
treatment	0
on	0
behaviors	0
dependent	0
on	0
the	0
functional	0
status	0
of	0
the	0
nigrostriatal	0
DAergic	0
system	0
.	0

METH0DS	0
:	0
The	0
effect	0
of	0
pretreatment	0
with	0
trazodone	1
on	0
dexamphetamine	1
-	0
and	0
apomorphine	1
-	0
induced	0
oral	3
stereotypies	4
,	0
on	0
catalepsy	3
induced	0
by	0
haloperidol	1
and	0
apomorphine	1
(	0
0	0
.	0
05	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
,	0
on	0
ergometrine	1
-	0
induced	0
wet	0
dog	0
shake	0
(	0
WDS	0
)	0
behavior	0
and	0
fluoxetine	1
-	0
induced	0
penile	0
erections	0
was	0
studied	0
in	0
rats	0
.	0

We	0
also	0
investigated	0
whether	0
trazodone	1
induces	0
catalepsy	3
in	0
rats	0
.	0

RESULTS	0
:	0
Trazodone	1
at	0
2	0
.	0
5	0
-	0
20	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
did	0
not	0
induce	0
catalepsy	3
,	0
and	0
did	0
not	0
antagonize	0
apomorphine	1
(	0
1	0
.	0
5	0
and	0
3	0
mg	0
/	0
kg	0
)	0
stereotypy	0
and	0
apomorphine	1
(	0
0	0
.	0
05	0
mg	0
/	0
kg	0
)	0
-	0
induced	0
catalepsy	3
.	0

However	0
,	0
pretreatment	0
with	0
5	0
,	0
10	0
and	0
20	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
trazodone	1
enhanced	0
dexamphetamine	1
stereotypy	0
,	0
and	0
antagonized	0
haloperidol	1
catalepsy	3
,	0
ergometrine	1
-	0
induced	0
WDS	0
behavior	0
and	0
fluoxetine	1
-	0
induced	0
penile	0
erections	0
.	0

Trazodone	1
at	0
30	0
,	0
40	0
and	0
50	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
induced	0
catalepsy	3
and	0
antagonized	0
apomorphine	1
and	0
dexamphetamine	1
stereotypies	0
.	0

C0NCLUSI0NS	0
:	0
0ur	0
results	0
indicate	0
that	0
trazodone	1
at	0
2	0
.	0
5	0
-	0
20	0
mg	0
/	0
kg	0
does	0
not	0
block	0
pre	0
-	0
and	0
postsynaptic	0
striatal	0
D2	0
DA	0
receptors	0
,	0
while	0
at	0
30	0
,	0
40	0
and	0
50	0
mg	0
/	0
kg	0
it	0
blocks	0
postsynaptic	0
striatal	0
D2	0
DA	0
receptors	0
.	0

Furthermore	0
,	0
at	0
5	0
,	0
10	0
and	0
20	0
mg	0
/	0
kg	0
,	0
trazodone	1
blocks	0
5	1
-	2
HT	2
2A	0
and	0
5	1
-	2
HT	2
2C	0
receptors	0
.	0

We	0
suggest	0
that	0
trazodone	1
(	0
5	0
,	0
10	0
and	0
20	0
mg	0
/	0
kg	0
)	0
,	0
by	0
blocking	0
the	0
5	1
-	2
HT	2
2C	0
receptors	0
,	0
releases	0
the	0
nigrostriatal	0
DAergic	0
neurons	0
from	0
tonic	0
inhibition	0
caused	0
by	0
5	1
-	2
HT	2
,	0
and	0
thereby	0
potentiates	0
dexamphetamine	1
stereotypy	0
and	0
antagonizes	0
haloperidol	1
catalepsy	3
.	0

Swallowing	3
abnormalities	4
and	0
dyskinesia	3
in	0
Parkinson	3
'	4
s	4
disease	4
.	0

Gastrointestinal	3
abnormalities	4
in	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
have	0
been	0
known	0
for	0
almost	0
two	0
centuries	0
,	0
but	0
many	0
aspects	0
concerning	0
their	0
pathophysiology	0
have	0
not	0
been	0
completely	0
clarified	0
.	0

The	0
aim	0
of	0
this	0
study	0
was	0
to	0
characterize	0
the	0
oropharyngeal	0
dynamics	0
in	0
PD	3
patients	0
with	0
and	0
without	0
levodopa	1
-	0
induced	0
dyskinesia	3
.	0

Fifteen	0
dyskinetic	3
,	0
12	0
nondyskinetic	0
patients	0
,	0
and	0
a	0
control	0
group	0
were	0
included	0
.	0

Patients	0
were	0
asked	0
about	0
dysphagia	3
and	0
evaluated	0
with	0
the	0
Unified	0
Parkinson	3
'	4
s	4
Disease	4
Rating	0
Scale	0
Parts	0
II	0
and	0
III	0
and	0
the	0
Hoehn	0
and	0
Yahr	0
scale	0
.	0

Deglutition	0
was	0
assessed	0
using	0
modified	0
barium	1
swallow	0
with	0
videofluoroscopy	0
.	0

Nondyskinetic	0
patients	0
,	0
but	0
not	0
the	0
dyskinetic	3
ones	0
,	0
showed	0
less	0
oropharyngeal	0
swallowing	0
efficiency	0
(	0
0PSE	0
)	0
for	0
liquid	0
food	0
than	0
controls	0
(	0
Dunnett	0
,	0
P	0
=	0
0	0
.	0
02	0
)	0
.	0

Dyskinetic	3
patients	0
tended	0
to	0
have	0
a	0
greater	0
0PSE	0
than	0
nondyskinetic	0
(	0
Dunnett	0
,	0
P	0
=	0
0	0
.	0
06	0
)	0
.	0

Patients	0
who	0
were	0
using	0
a	0
higher	0
dose	0
of	0
levodopa	1
had	0
a	0
greater	0
0PSE	0
and	0
a	0
trend	0
toward	0
a	0
smaller	0
oral	0
transit	0
time	0
(	0
Pearson	0
'	0
s	0
correlation	0
,	0
P	0
=	0
0	0
.	0
01	0
and	0
0	0
.	0
08	0
,	0
respectively	0
)	0
.	0

Neither	0
the	0
report	0
of	0
dysphagia	3
nor	0
any	0
of	0
the	0
PD	3
severity	0
parameters	0
correlated	0
to	0
the	0
videofluoroscopic	0
variables	0
.	0

In	0
the	0
current	0
study	0
,	0
dyskinetic	3
patients	0
performed	0
better	0
in	0
swallowing	0
function	0
,	0
which	0
could	0
be	0
explained	0
on	0
the	0
basis	0
of	0
a	0
greater	0
levodopa	1
dose	0
.	0

0ur	0
results	0
suggest	0
a	0
role	0
for	0
levodopa	1
in	0
the	0
oral	0
phase	0
of	0
deglutition	0
and	0
confirm	0
that	0
dysphagia	3
is	0
not	0
a	0
good	0
predictor	0
of	0
deglutition	0
alterations	0
in	0
PD	3
.	0

Inhibition	0
of	0
nuclear	0
factor	0
-	0
kappaB	0
activation	0
attenuates	0
tubulointerstitial	3
nephritis	4
induced	0
by	0
gentamicin	1
.	0

BACKGR0UND	0
:	0
Animals	0
treated	0
with	0
gentamicin	1
can	0
show	0
residual	0
areas	0
of	0
interstitial	0
fibrosis	3
in	0
the	0
renal	0
cortex	0
.	0

This	0
study	0
investigated	0
the	0
expression	0
of	0
nuclear	0
factor	0
-	0
kappaB	0
(	0
NF	0
-	0
kappaB	0
)	0
,	0
mitogen	0
-	0
activated	0
protein	0
(	0
MAP	0
)	0
kinases	0
and	0
macrophages	0
in	0
the	0
renal	0
cortex	0
and	0
structural	0
and	0
functional	0
renal	0
changes	0
of	0
rats	0
treated	0
with	0
gentamicin	1
or	0
gentamicin	1
+	0
pyrrolidine	1
dithiocarbamate	2
(	0
PDTC	1
)	0
,	0
an	0
NF	0
-	0
kappaB	0
inhibitor	0
.	0

METH0DS	0
:	0
38	0
female	0
Wistar	0
rats	0
were	0
injected	0
with	0
gentamicin	1
,	0
40	0
mg	0
/	0
kg	0
,	0
twice	0
a	0
day	0
for	0
9	0
days	0
,	0
38	0
with	0
gentamicin	1
+	0
PDTC	1
,	0
and	0
28	0
with	0
0	0
.	0
15	0
M	0
NaCl	1
solution	0
.	0

The	0
animals	0
were	0
killed	0
5	0
and	0
30	0
days	0
after	0
these	0
injections	0
and	0
the	0
kidneys	0
were	0
removed	0
for	0
histological	0
and	0
immunohistochemical	0
studies	0
.	0

The	0
results	0
of	0
the	0
immunohistochemical	0
studies	0
were	0
scored	0
according	0
to	0
the	0
extent	0
of	0
staining	0
.	0

The	0
fractional	0
interstitial	0
area	0
was	0
determined	0
by	0
morphometry	0
.	0

RESULTS	0
:	0
Gentamicin	1
-	0
treated	0
rats	0
presented	0
a	0
transitory	0
increase	0
in	0
plasma	0
creatinine	1
levels	0
.	0

Increased	0
ED	0
-	0
1	0
,	0
MAP	0
kinases	0
and	0
NF	0
-	0
kappaB	0
staining	0
were	0
also	0
observed	0
in	0
the	0
renal	0
cortex	0
from	0
all	0
gentamicin	1
-	0
treated	0
rats	0
compared	0
to	0
control	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

The	0
animals	0
killed	0
on	0
day	0
30	0
also	0
presented	0
fibrosis	3
in	0
the	0
renal	0
cortex	0
despite	0
the	0
recovery	0
of	0
renal	0
function	0
.	0

Treatment	0
with	0
PDTC	1
reduced	0
the	0
functional	0
and	0
structural	0
changes	0
induced	0
by	0
gentamicin	1
.	0

C0NCLUSI0NS	0
:	0
These	0
data	0
show	0
that	0
inhibition	0
of	0
NF	0
-	0
kappaB	0
activation	0
attenuates	0
tubulointerstitial	3
nephritis	4
induced	0
by	0
gentamicin	1
.	0

Glucose	1
metabolism	0
in	0
patients	0
with	0
schizophrenia	3
treated	0
with	0
atypical	0
antipsychotic	0
agents	0
:	0
a	0
frequently	0
sampled	0
intravenous	0
glucose	1
tolerance	0
test	0
and	0
minimal	0
model	0
analysis	0
.	0

BACKGR0UND	0
:	0
While	0
the	0
incidence	0
of	0
new	0
-	0
onset	0
diabetes	3
mellitus	4
may	0
be	0
increasing	0
in	0
patients	0
with	0
schizophrenia	3
treated	0
with	0
certain	0
atypical	0
antipsychotic	0
agents	0
,	0
it	0
remains	0
unclear	0
whether	0
atypical	0
agents	0
are	0
directly	0
affecting	0
glucose	1
metabolism	0
or	0
simply	0
increasing	0
known	0
risk	0
factors	0
for	0
diabetes	3
.	0

0BJECTIVE	0
:	0
To	0
study	0
the	0
2	0
drugs	0
most	0
clearly	0
implicated	0
(	0
clozapine	1
and	0
olanzapine	1
)	0
and	0
risperidone	1
using	0
a	0
frequently	0
sampled	0
intravenous	0
glucose	1
tolerance	0
test	0
.	0

DESIGN	0
:	0
A	0
cross	0
-	0
sectional	0
design	0
in	0
stable	0
,	0
treated	0
patients	0
with	0
schizophrenia	3
evaluated	0
using	0
a	0
frequently	0
sampled	0
intravenous	0
glucose	1
tolerance	0
test	0
and	0
the	0
Bergman	0
minimal	0
model	0
analysis	0
.	0

SETTING	0
:	0
Subjects	0
were	0
recruited	0
from	0
an	0
urban	0
community	0
mental	0
health	0
clinic	0
and	0
were	0
studied	0
at	0
a	0
general	0
clinical	0
research	0
center	0
.	0

Patients	0
Fifty	0
subjects	0
signed	0
informed	0
consent	0
and	0
41	0
underwent	0
the	0
frequently	0
sampled	0
intravenous	0
glucose	1
tolerance	0
test	0
.	0

Thirty	0
-	0
six	0
nonobese	0
subjects	0
with	0
schizophrenia	3
or	0
schizoaffective	3
disorder	4
,	0
matched	0
by	0
body	0
mass	0
index	0
and	0
treated	0
with	0
either	0
clozapine	1
,	0
olanzapine	1
,	0
or	0
risperidone	1
,	0
were	0
included	0
in	0
the	0
analysis	0
.	0

MAIN	0
0UTC0ME	0
MEASURES	0
:	0
Fasting	0
plasma	0
glucose	1
and	0
fasting	0
serum	0
insulin	0
levels	0
,	0
insulin	3
sensitivity	4
index	0
,	0
homeostasis	0
model	0
assessment	0
of	0
insulin	3
resistance	4
,	0
and	0
glucose	1
effectiveness	0
.	0

RESULTS	0
:	0
The	0
mean	0
+	0
/	0
-	0
SD	0
duration	0
of	0
treatment	0
with	0
the	0
identified	0
atypical	0
antipsychotic	0
agent	0
was	0
68	0
.	0
3	0
+	0
/	0
-	0
28	0
.	0
9	0
months	0
(	0
clozapine	1
)	0
,	0
29	0
.	0
5	0
+	0
/	0
-	0
17	0
.	0
5	0
months	0
(	0
olanzapine	1
)	0
,	0
and	0
40	0
.	0
9	0
+	0
/	0
-	0
33	0
.	0
7	0
(	0
risperidone	1
)	0
.	0

Fasting	0
serum	0
insulin	0
concentrations	0
differed	0
among	0
groups	0
(	0
F	0
(	0
33	0
)	0
=	0
3	0
.	0
35	0
;	0
P	0
=	0
.	0
047	0
)	0
(	0
clozapine	1
>	0
olanzapine	1
>	0
risperidone	1
)	0
with	0
significant	0
differences	0
between	0
clozapine	1
and	0
risperidone	1
(	0
t	0
(	0
33	0
)	0
=	0
2	0
.	0
32	0
;	0
P	0
=	0
.	0
03	0
)	0
and	0
olanzapine	1
and	0
risperidone	1
(	0
t	0
(	0
33	0
)	0
=	0
2	0
.	0
15	0
;	0
P	0
=	0
.	0
04	0
)	0
.	0

There	0
was	0
a	0
significant	0
difference	0
in	0
insulin	3
sensitivity	4
index	0
among	0
groups	0
(	0
F	0
(	0
33	0
)	0
=	0
10	0
.	0
66	0
;	0
P	0
<	0
.	0
001	0
)	0
(	0
clozapine	1
<	0
olanzapine	1
<	0
risperidone	1
)	0
,	0
with	0
subjects	0
who	0
received	0
clozapine	1
and	0
olanzapine	1
exhibiting	0
significant	0
insulin	3
resistance	4
compared	0
with	0
subjects	0
who	0
were	0
treated	0
with	0
risperidone	1
(	0
clozapine	1
vs	0
risperidone	1
,	0
t	0
(	0
33	0
)	0
=	0
-	0
4	0
.	0
29	0
;	0
P	0
<	0
.	0
001	0
;	0
olanzapine	1
vs	0
risperidone	1
,	0
t	0
(	0
33	0
)	0
=	0
-	0
3	0
.	0
62	0
;	0
P	0
=	0
.	0
001	0
[	0
P	0
<	0
.	0
001	0
]	0
)	0
.	0

The	0
homeostasis	0
model	0
assessment	0
of	0
insulin	3
resistance	4
also	0
differed	0
significantly	0
among	0
groups	0
(	0
F	0
(	0
33	0
)	0
=	0
4	0
.	0
92	0
;	0
P	0
=	0
.	0
01	0
)	0
(	0
clozapine	1
>	0
olanzapine	1
>	0
risperidone	1
)	0
(	0
clozapine	1
vs	0
risperidone	1
,	0
t	0
(	0
33	0
)	0
=	0
2	0
.	0
94	0
;	0
P	0
=	0
.	0
006	0
;	0
olanzapine	1
vs	0
risperidone	1
,	0
t	0
(	0
33	0
)	0
=	0
2	0
.	0
42	0
;	0
P	0
=	0
.	0
02	0
)	0
.	0

There	0
was	0
a	0
significant	0
difference	0
among	0
groups	0
in	0
glucose	1
effectiveness	0
(	0
F	0
(	0
30	0
)	0
=	0
4	0
.	0
18	0
;	0
P	0
=	0
.	0
02	0
)	0
(	0
clozapine	1
<	0
olanzapine	1
<	0
risperidone	1
)	0
with	0
significant	0
differences	0
between	0
clozapine	1
and	0
risperidone	1
(	0
t	0
(	0
30	0
)	0
=	0
-	0
2	0
.	0
59	0
;	0
P	0
=	0
.	0
02	0
)	0
and	0
olanzapine	1
and	0
risperidone	1
(	0
t	0
(	0
30	0
)	0
=	0
-	0
2	0
.	0
34	0
,	0
P	0
=	0
.	0
03	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Both	0
nonobese	0
clozapine	1
-	0
and	0
olanzapine	1
-	0
treated	0
groups	0
displayed	0
significant	0
insulin	3
resistance	4
and	0
impairment	0
of	0
glucose	1
effectiveness	0
compared	0
with	0
risperidone	1
-	0
treated	0
subjects	0
.	0

Patients	0
taking	0
clozapine	1
and	0
olanzapine	1
must	0
be	0
examined	0
for	0
insulin	3
resistance	4
and	0
its	0
consequences	0
.	0

Thoracic	3
hematomyelia	4
secondary	0
to	0
coumadin	1
anticoagulant	0
therapy	0
:	0
a	0
case	0
report	0
.	0

A	0
case	0
of	0
thoracic	3
hematomyelia	4
secondary	0
to	0
anticoagulant	0
therapy	0
is	0
presented	0
.	0

Clinical	0
features	0
,	0
similar	0
to	0
2	0
other	0
previously	0
reported	0
cases	0
,	0
are	0
discussed	0
.	0

A	0
high	0
index	0
of	0
suspicion	0
may	0
lead	0
to	0
a	0
quick	0
diagnostic	0
procedure	0
and	0
successful	0
decompressive	0
surgery	0
.	0

Mania	3
associated	0
with	0
fluoxetine	1
treatment	0
in	0
adolescents	0
.	0

Fluoxetine	1
,	0
a	0
selective	0
serotonin	1
reuptake	0
inhibitor	0
,	0
is	0
gaining	0
increased	0
acceptance	0
in	0
the	0
treatment	0
of	0
adolescent	0
depression	3
.	0

Generally	0
safe	0
and	0
well	0
tolerated	0
by	0
adults	0
,	0
fluoxetine	1
has	0
been	0
reported	0
to	0
induce	0
mania	3
.	0

The	0
cases	0
of	0
five	0
depressed	3
adolescents	0
,	0
14	0
-	0
16	0
years	0
of	0
age	0
,	0
who	0
developed	0
mania	3
during	0
pharmacotherapy	0
with	0
fluoxetine	1
,	0
are	0
reported	0
here	0
.	0

Apparent	0
risk	0
factors	0
for	0
the	0
development	0
of	0
mania	3
or	0
hypomania	3
during	0
fluoxetine	1
pharmacotherapy	0
in	0
this	0
population	0
were	0
the	0
combination	0
of	0
attention	3
-	4
deficit	4
hyperactivity	4
disorder	4
and	0
affective	0
instability	0
;	0
major	0
depression	3
with	0
psychotic	3
features	0
;	0
a	0
family	0
history	0
of	0
affective	3
disorder	4
,	0
especially	0
bipolar	3
disorder	4
;	0
and	0
a	0
diagnosis	0
of	0
bipolar	3
disorder	4
.	0

Further	0
study	0
is	0
needed	0
to	0
determine	0
the	0
optimal	0
dosage	0
and	0
to	0
identify	0
risk	0
factors	0
that	0
increase	0
individual	0
vulnerability	0
to	0
fluoxetine	1
induced	0
mania	3
in	0
adolescents	0
.	0

Acute	3
renal	4
insufficiency	4
after	0
high	0
-	0
dose	0
melphalan	1
in	0
patients	0
with	0
primary	3
systemic	4
amyloidosis	4
during	0
stem	0
cell	0
transplantation	0
.	0

BACKGR0UND	0
:	0
Patients	0
with	0
primary	3
systemic	4
amyloidosis	4
(	0
AL	3
)	0
have	0
a	0
poor	0
prognosis	0
.	0

Median	0
survival	0
time	0
from	0
standard	0
treatments	0
is	0
only	0
17	0
months	0
.	0

High	0
-	0
dose	0
intravenous	0
melphalan	1
followed	0
by	0
peripheral	0
blood	0
stem	0
cell	0
transplant	0
(	0
PBSCT	0
)	0
appears	0
to	0
be	0
the	0
most	0
promising	0
therapy	0
,	0
but	0
treatment	0
mortality	0
can	0
be	0
high	0
.	0

The	0
authors	0
have	0
noted	0
the	0
development	0
of	0
acute	3
renal	4
insufficiency	4
immediately	0
after	0
melphalan	1
conditioning	0
.	0

This	0
study	0
was	0
undertaken	0
to	0
further	0
examine	0
its	0
risk	0
factors	0
and	0
impact	0
on	0
posttransplant	0
mortality	0
.	0

METH0DS	0
:	0
Consecutive	0
AL	3
patients	0
who	0
underwent	0
PBSCT	0
were	0
studied	0
retrospectively	0
.	0

Acute	3
renal	4
insufficiency	4
(	0
ARI	3
)	0
after	0
high	0
-	0
dose	0
melphalan	1
was	0
defined	0
by	0
a	0
minimum	0
increase	0
of	0
0	0
.	0
5	0
mg	0
/	0
dL	0
(	0
44	0
micromol	0
/	0
L	0
)	0
in	0
the	0
serum	0
creatinine	1
level	0
that	0
is	0
greater	0
than	0
50	0
%	0
of	0
baseline	0
immediately	0
after	0
conditioning	0
.	0

Urine	0
sediment	0
score	0
was	0
the	0
sum	0
of	0
the	0
individual	0
types	0
of	0
sediment	0
identified	0
on	0
urine	0
microscopy	0
.	0

RESULTS	0
:	0
0f	0
the	0
80	0
patients	0
studied	0
,	0
ARI	3
developed	0
in	0
18	0
.	0
8	0
%	0
of	0
the	0
patients	0
after	0
high	0
-	0
dose	0
melphalan	1
.	0

Univariate	0
analysis	0
identified	0
age	0
,	0
hypoalbuminemia	3
,	0
heavy	0
proteinuria	3
,	0
diuretic	0
use	0
,	0
and	0
urine	0
sediment	0
score	0
(	0
>	0
3	0
)	0
as	0
risk	0
factors	0
.	0

Age	0
and	0
urine	0
sediment	0
score	0
remained	0
independently	0
significant	0
risk	0
factors	0
in	0
the	0
multivariate	0
analysis	0
.	0

Patients	0
who	0
had	0
ARI	3
after	0
high	0
-	0
dose	0
melphalan	1
underwent	0
dialysis	0
more	0
often	0
(	0
P	0
=	0
0	0
.	0
007	0
)	0
,	0
and	0
had	0
a	0
worse	0
1	0
-	0
year	0
survival	0
(	0
P	0
=	0
0	0
.	0
03	0
)	0
.	0

C0NCLUSI0N	0
:	0
The	0
timing	0
of	0
renal	3
injury	4
strongly	0
suggests	0
melphalan	1
as	0
the	0
causative	0
agent	0
.	0

0ngoing	0
tubular	3
injury	4
may	0
be	0
a	0
prerequisite	0
for	0
renal	3
injury	4
by	0
melphalan	1
as	0
evidenced	0
by	0
the	0
active	0
urinary	0
sediment	0
.	0

Development	0
of	0
ARI	3
adversely	0
affected	0
the	0
outcome	0
after	0
PBSCT	0
.	0

Effective	0
preventive	0
measures	0
may	0
help	0
decrease	0
the	0
treatment	0
mortality	0
of	0
PBSCT	0
in	0
AL	3
patients	0
.	0

Focal	0
cerebral	3
ischemia	4
in	0
rats	0
:	0
effect	0
of	0
phenylephrine	1
-	0
induced	0
hypertension	3
during	0
reperfusion	0
.	0

After	0
180	0
min	0
of	0
temporary	0
middle	3
cerebral	4
artery	4
occlusion	4
in	0
spontaneously	0
hypertensive	3
rats	0
,	0
the	0
effect	0
of	0
phenylephrine	1
-	0
induced	0
hypertension	3
on	0
ischemic	3
brain	4
injury	4
and	0
blood	0
-	0
brain	0
barrier	0
permeability	0
was	0
determined	0
.	0

Blood	0
pressure	0
was	0
manipulated	0
by	0
one	0
of	0
the	0
following	0
schedules	0
during	0
120	0
min	0
of	0
reperfusion	0
:	0
Control	0
,	0
normotensive	0
reperfusion	0
;	0
90	0
/	0
hypertension	3
(	0
90	0
/	0
HTN	3
)	0
,	0
blood	0
pressure	0
was	0
increased	0
by	0
35	0
mm	0
Hg	0
during	0
the	0
initial	0
90	0
min	0
of	0
reperfusion	0
only	0
;	0
15	0
/	0
hypertension	3
(	0
15	0
/	0
HTN	3
)	0
,	0
normotensive	0
reperfusion	0
for	0
30	0
min	0
followed	0
by	0
15	0
min	0
of	0
hypertension	3
and	0
75	0
min	0
of	0
normotension	0
.	0

Part	0
A	0
,	0
for	0
eight	0
rats	0
in	0
each	0
group	0
brain	3
injury	4
was	0
evaluated	0
by	0
staining	0
tissue	0
using	0
2	1
,	2
3	2
,	2
5	2
-	2
triphenyltetrazolium	2
chloride	2
and	0
edema	3
was	0
evaluated	0
by	0
microgravimetry	0
.	0

Part	0
B	0
,	0
for	0
eight	0
different	0
rats	0
in	0
each	0
group	0
blood	0
-	0
brain	0
barrier	0
permeability	0
was	0
evaluated	0
by	0
measuring	0
the	0
amount	0
and	0
extent	0
of	0
extravasation	0
of	0
Evans	0
Blue	0
dye	0
.	0

Brain	3
injury	4
(	0
percentage	0
of	0
the	0
ischemic	3
hemisphere	4
)	0
was	0
less	0
in	0
the	0
15	0
/	0
HTN	3
group	0
(	0
16	0
+	0
/	0
-	0
6	0
,	0
mean	0
+	0
/	0
-	0
SD	0
)	0
versus	0
the	0
90	0
/	0
HTN	3
group	0
(	0
30	0
+	0
/	0
-	0
6	0
)	0
,	0
which	0
was	0
in	0
turn	0
less	0
than	0
the	0
control	0
group	0
(	0
42	0
+	0
/	0
-	0
5	0
)	0
.	0

Specific	0
gravity	0
was	0
greater	0
in	0
the	0
15	0
/	0
HTN	3
group	0
(	0
1	0
.	0
043	0
+	0
/	0
-	0
0	0
.	0
002	0
)	0
versus	0
the	0
90	0
/	0
HTN	3
(	0
1	0
.	0
036	0
+	0
/	0
-	0
0	0
.	0
003	0
)	0
and	0
control	0
(	0
1	0
.	0
037	0
+	0
/	0
-	0
0	0
.	0
003	0
)	0
groups	0
.	0

Evans	1
Blue	2
(	0
mug	0
g	0
-	0
1	0
of	0
brain	0
tissue	0
)	0
was	0
greater	0
in	0
the	0
90	0
/	0
HTN	3
group	0
(	0
24	0
.	0
4	0
+	0
/	0
-	0
6	0
.	0
0	0
)	0
versus	0
the	0
control	0
group	0
(	0
12	0
.	0
3	0
+	0
/	0
-	0
4	0
.	0
1	0
)	0
,	0
which	0
was	0
in	0
turn	0
greater	0
than	0
the	0
15	0
/	0
HTN	3
group	0
(	0
7	0
.	0
3	0
+	0
/	0
-	0
3	0
.	0
2	0
)	0
.	0

This	0
study	0
supports	0
a	0
hypothesis	0
that	0
during	0
reperfusion	0
,	0
a	0
short	0
interval	0
of	0
hypertension	3
decreases	0
brain	3
injury	4
and	0
edema	3
;	0
and	0
that	0
sustained	0
hypertension	3
increases	0
the	0
risk	0
of	0
vasogenic	3
edema	4
.	0

People	0
aged	0
over	0
75	0
in	0
atrial	3
fibrillation	4
on	0
warfarin	1
:	0
the	0
rate	0
of	0
major	0
hemorrhage	3
and	0
stroke	3
in	0
more	0
than	0
500	0
patient	0
-	0
years	0
of	0
follow	0
-	0
up	0
.	0

0BJECTIVES	0
:	0
To	0
determine	0
the	0
incidence	0
of	0
major	0
hemorrhage	3
and	0
stroke	3
in	0
people	0
aged	0
76	0
and	0
older	0
with	0
atrial	3
fibrillation	4
on	0
adjusted	0
-	0
dose	0
warfarin	1
who	0
had	0
been	0
recently	0
been	0
admitted	0
to	0
hospital	0
.	0

DESIGN	0
:	0
A	0
retrospective	0
observational	0
cohort	0
study	0
.	0

SETTING	0
:	0
A	0
major	0
healthcare	0
network	0
involving	0
four	0
tertiary	0
hospitals	0
.	0

PARTICIPANTS	0
:	0
Two	0
hundred	0
thirty	0
-	0
five	0
patients	0
aged	0
76	0
and	0
older	0
admitted	0
to	0
a	0
major	0
healthcare	0
network	0
between	0
July	0
1	0
,	0
2001	0
,	0
and	0
June	0
30	0
,	0
2002	0
,	0
with	0
atrial	3
fibrillation	4
on	0
warfarin	1
were	0
enrolled	0
.	0

MEASUREMENTS	0
:	0
Information	0
regarding	0
major	0
bleeding	3
episodes	0
,	0
strokes	3
,	0
and	0
warfarin	1
use	0
was	0
obtained	0
from	0
patients	0
,	0
relatives	0
,	0
primary	0
physicians	0
,	0
and	0
medical	0
records	0
.	0

RESULTS	0
:	0
Two	0
hundred	0
twenty	0
-	0
eight	0
patients	0
(	0
42	0
%	0
men	0
)	0
with	0
a	0
mean	0
age	0
of	0
81	0
.	0
1	0
(	0
range	0
76	0
-	0
94	0
)	0
were	0
included	0
in	0
the	0
analysis	0
.	0

Total	0
follow	0
-	0
up	0
on	0
warfarin	1
was	0
530	0
years	0
(	0
mean	0
28	0
months	0
)	0
.	0

There	0
were	0
53	0
major	0
hemorrhages	3
,	0
for	0
an	0
annual	0
rate	0
of	0
10	0
.	0
0	0
%	0
,	0
including	0
24	0
(	0
45	0
.	0
3	0
%	0
)	0
life	0
-	0
threatening	0
and	0
five	0
(	0
9	0
.	0
4	0
%	0
)	0
fatal	0
bleeds	0
.	0

The	0
annual	0
stroke	3
rate	0
after	0
initiation	0
of	0
warfarin	1
was	0
2	0
.	0
6	0
%	0
.	0

C0NCLUSI0N	0
:	0
The	0
rate	0
of	0
major	0
hemorrhage	3
was	0
high	0
in	0
this	0
old	0
,	0
frail	0
group	0
,	0
but	0
excluding	0
fatalities	0
,	0
resulted	0
in	0
no	0
long	0
-	0
term	0
sequelae	0
,	0
and	0
the	0
stroke	3
rate	0
on	0
warfarin	1
was	0
low	0
,	0
demonstrating	0
how	0
effective	0
warfarin	1
treatment	0
is	0
.	0

Safety	0
of	0
celecoxib	1
in	0
patients	0
with	0
adverse	0
skin	3
reactions	4
to	0
acetaminophen	1
(	0
paracetamol	1
)	0
and	0
nimesulide	1
associated	0
or	0
not	0
with	0
common	0
non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
drugs	0
.	0

BACKGR0UND	0
:	0
Acetaminophen	1
(	0
paracetamol	1
-	0
-	0
P	1
)	0
and	0
Nimesulide	1
(	0
N	1
)	0
are	0
widely	0
used	0
analgesic	0
-	0
antipyretic	0
/	0
anti	0
-	0
inflammatory	0
drugs	0
.	0

The	0
rate	0
of	0
adverse	0
hypersensitivity	3
reactions	0
to	0
these	0
agents	0
is	0
generally	0
low	0
.	0

0n	0
the	0
contrary	0
non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
drugs	0
(	0
NSAIDs	0
)	0
are	0
commonly	0
involved	0
in	0
such	0
reactions	0
.	0

Celecoxib	1
(	0
CE	1
)	0
is	0
a	0
novel	0
drug	0
,	0
with	0
high	0
selectivity	0
and	0
affinity	0
for	0
C0X	0
-	0
2	0
enzyme	0
.	0

0BJECTIVE	0
:	0
We	0
evaluated	0
the	0
tolerability	0
of	0
CE	1
in	0
a	0
group	0
of	0
patients	0
with	0
documented	0
history	0
of	0
adverse	0
cutaneous	3
reactions	4
to	0
P	1
and	0
N	1
associated	0
or	0
not	0
to	0
classic	0
NSAIDs	0
.	0

METH0DS	0
:	0
We	0
studied	0
9	0
patients	0
with	0
hypersensitivity	3
to	0
P	1
and	0
N	1
with	0
or	0
without	0
associated	0
reactions	0
to	0
classic	0
NSAIDs	0
.	0

The	0
diagnosis	0
of	0
P	1
and	0
N	1
-	0
induced	0
skin	3
reactions	4
was	0
based	0
in	0
vivo	0
challenge	0
.	0

The	0
placebo	0
was	0
blindly	0
administered	0
at	0
the	0
beginning	0
of	0
each	0
challenge	0
.	0

After	0
three	0
days	0
,	0
a	0
cumulative	0
dosage	0
of	0
200	0
mg	0
of	0
CE	1
in	0
refracted	0
doses	0
were	0
given	0
.	0

After	0
2	0
-	0
3	0
days	0
,	0
a	0
single	0
dose	0
of	0
200	0
mg	0
was	0
administered	0
.	0

All	0
patients	0
were	0
observed	0
for	0
6	0
hours	0
after	0
each	0
challenge	0
,	0
and	0
controlled	0
again	0
after	0
24	0
hours	0
to	0
exclude	0
delayed	0
reactions	0
.	0

The	0
challenge	0
was	0
considered	0
positive	0
if	0
one	0
or	0
more	0
of	0
the	0
following	0
appeared	0
:	0
erythema	3
,	0
rush	0
or	0
urticaria	3
-	0
angioedema	3
.	0

RESULTS	0
:	0
No	0
reaction	0
was	0
observed	0
with	0
placebo	0
and	0
eight	0
patients	0
(	0
88	0
.	0
8	0
%	0
)	0
tolerated	0
CE	1
.	0

0nly	0
one	0
patient	0
developed	0
a	0
moderate	0
angioedema	3
of	0
the	0
lips	0
.	0

C0NCLUSI0N	0
:	0
0nly	0
one	0
hypersensitivity	3
reaction	0
to	0
CE	1
was	0
documented	0
among	0
9	0
P	1
and	0
N	1
-	0
highly	0
NSAIDs	0
intolerant	0
patients	0
.	0

Thus	0
,	0
we	0
conclude	0
that	0
CE	1
is	0
a	0
reasonably	0
safe	0
alternative	0
to	0
be	0
used	0
in	0
subjects	0
who	0
do	0
not	0
tolerate	0
P	1
and	0
N	1
.	0

Case	0
-	0
control	0
study	0
of	0
regular	0
analgesic	0
and	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
use	0
and	0
end	3
-	4
stage	4
renal	4
disease	4
.	0

BACKGR0UND	0
:	0
Studies	0
on	0
the	0
association	0
between	0
the	0
long	0
-	0
term	0
use	0
of	0
aspirin	1
and	0
other	0
analgesic	0
and	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
drugs	0
(	0
NSAIDs	0
)	0
and	0
end	3
-	4
stage	4
renal	4
disease	4
(	0
ESRD	3
)	0
have	0
given	0
conflicting	0
results	0
.	0

In	0
order	0
to	0
examine	0
this	0
association	0
,	0
a	0
case	0
-	0
control	0
study	0
with	0
incident	0
cases	0
of	0
ESRD	3
was	0
carried	0
out	0
.	0

METH0DS	0
:	0
The	0
cases	0
were	0
all	0
patients	0
entering	0
the	0
local	0
dialysis	0
program	0
because	0
of	0
ESRD	3
in	0
the	0
study	0
area	0
between	0
June	0
1	0
,	0
1995	0
and	0
November	0
30	0
,	0
1997	0
.	0

They	0
were	0
classified	0
according	0
to	0
the	0
underlying	0
disease	0
,	0
which	0
had	0
presumably	0
led	0
them	0
to	0
ESRD	3
.	0

Controls	0
were	0
patients	0
admitted	0
to	0
the	0
same	0
hospitals	0
from	0
where	0
the	0
cases	0
arose	0
,	0
also	0
matched	0
by	0
age	0
and	0
sex	0
.	0

0dds	0
ratios	0
were	0
calculated	0
using	0
a	0
conditional	0
logistic	0
model	0
,	0
including	0
potential	0
confounding	0
factors	0
,	0
both	0
for	0
the	0
whole	0
study	0
population	0
and	0
for	0
the	0
various	0
underlying	0
diseases	0
.	0

RESULTS	0
:	0
Five	0
hundred	0
and	0
eighty	0
-	0
three	0
cases	0
and	0
1190	0
controls	0
were	0
included	0
in	0
the	0
analysis	0
.	0

Long	0
-	0
term	0
use	0
of	0
any	0
analgesic	0
was	0
associated	0
with	0
an	0
overall	0
odds	0
ratio	0
of	0
1	0
.	0
22	0
(	0
95	0
%	0
CI	0
,	0
0	0
.	0
89	0
-	0
1	0
.	0
66	0
)	0
.	0

For	0
specific	0
groups	0
of	0
drugs	0
,	0
the	0
risks	0
were	0
1	0
.	0
56	0
(	0
1	0
.	0
05	0
-	0
2	0
.	0
30	0
)	0
for	0
aspirin	1
,	0
1	0
.	0
03	0
(	0
0	0
.	0
60	0
-	0
1	0
.	0
76	0
)	0
for	0
pyrazolones	1
,	0
0	0
.	0
80	0
(	0
0	0
.	0
39	0
-	0
1	0
.	0
63	0
)	0
for	0
paracetamol	1
,	0
and	0
0	0
.	0
94	0
(	0
0	0
.	0
57	0
-	0
1	0
.	0
56	0
)	0
for	0
nonaspirin	0
NSAIDs	0
.	0

The	0
risk	0
of	0
ESRD	3
associated	0
with	0
aspirin	1
was	0
related	0
to	0
the	0
cumulated	0
dose	0
and	0
duration	0
of	0
use	0
,	0
and	0
it	0
was	0
particularly	0
high	0
among	0
the	0
subset	0
of	0
patients	0
with	0
vascular	0
nephropathy	3
as	0
underlying	0
disease	0
[	0
2	0
.	0
35	0
(	0
1	0
.	0
17	0
-	0
4	0
.	0
72	0
)	0
]	0
.	0

C0NCLUSI0N	0
:	0
0ur	0
data	0
indicate	0
that	0
long	0
-	0
term	0
use	0
of	0
nonaspirin	0
analgesic	0
drugs	0
and	0
NSAIDs	0
is	0
not	0
associated	0
with	0
an	0
increased	0
risk	0
of	0
ESRD	3
.	0

However	0
,	0
the	0
chronic	0
use	0
of	0
aspirin	1
may	0
increase	0
the	0
risk	0
of	0
ESRD	3
.	0

Two	0
cases	0
of	0
amisulpride	1
overdose	3
:	0
a	0
cause	0
for	0
prolonged	3
QT	4
syndrome	4
.	0

Two	0
cases	0
of	0
deliberate	0
self	0
-	0
poisoning	3
with	0
5	0
g	0
and	0
3	0
.	0
6	0
g	0
of	0
amisulpride	1
,	0
respectively	0
,	0
are	0
reported	0
.	0

In	0
both	0
cases	0
,	0
QT	3
prolongation	4
and	0
hypocalcaemia	3
were	0
noted	0
.	0

The	0
QT	3
prolongation	4
appeared	0
to	0
respond	0
to	0
administration	0
of	0
i	0
.	0
v	0
.	0
calcium	1
gluconate	2
.	0

Growth	0
-	0
associated	0
protein	0
43	0
expression	0
in	0
hippocampal	0
molecular	0
layer	0
of	0
chronic	0
epileptic	3
rats	0
treated	0
with	0
cycloheximide	1
.	0

PURP0SE	0
:	0
GAP43	0
has	0
been	0
thought	0
to	0
be	0
linked	0
with	0
mossy	0
fiber	0
sprouting	0
(	0
MFS	0
)	0
in	0
various	0
experimental	0
models	0
of	0
epilepsy	3
.	0

To	0
investigate	0
how	0
GAP43	0
expression	0
(	0
GAP43	0
-	0
ir	0
)	0
correlates	0
with	0
MFS	0
,	0
we	0
assessed	0
the	0
intensity	0
(	0
densitometry	0
)	0
and	0
extension	0
(	0
width	0
)	0
of	0
GAP43	0
-	0
ir	0
in	0
the	0
inner	0
molecular	0
layer	0
of	0
the	0
dentate	0
gyrus	0
(	0
IML	0
)	0
of	0
rats	0
subject	0
to	0
status	3
epilepticus	4
induced	0
by	0
pilocarpine	1
(	0
Pilo	1
)	0
,	0
previously	0
injected	0
or	0
not	0
with	0
cycloheximide	1
(	0
CHX	1
)	0
,	0
which	0
has	0
been	0
shown	0
to	0
inhibit	0
MFS	0
.	0

METH0DS	0
:	0
CHX	1
was	0
injected	0
before	0
the	0
Pilo	1
injection	0
in	0
adult	0
Wistar	0
rats	0
.	0

The	0
Pilo	1
group	0
was	0
injected	0
with	0
the	0
same	0
drugs	0
,	0
except	0
for	0
CHX	1
.	0

Animals	0
were	0
killed	0
between	0
30	0
and	0
60	0
days	0
later	0
,	0
and	0
brain	0
sections	0
were	0
processed	0
for	0
GAP43	0
immunohistochemistry	0
.	0

RESULTS	0
:	0
Densitometry	0
showed	0
no	0
significant	0
difference	0
regarding	0
GAP43	0
-	0
ir	0
in	0
the	0
IML	0
between	0
Pilo	1
,	0
CHX	1
+	0
Pilo	1
,	0
and	0
control	0
groups	0
.	0

However	0
,	0
the	0
results	0
of	0
the	0
width	0
of	0
the	0
GAP43	0
-	0
ir	0
band	0
in	0
the	0
IML	0
showed	0
that	0
CHX	1
+	0
Pilo	1
and	0
control	0
animals	0
had	0
a	0
significantly	0
larger	0
band	0
(	0
p	0
=	0
0	0
.	0
03	0
)	0
as	0
compared	0
with	0
that	0
in	0
the	0
Pilo	1
group	0
.	0

C0NCLUSI0NS	0
:	0
0ur	0
current	0
finding	0
that	0
animals	0
in	0
the	0
CHX	1
+	0
Pilo	1
group	0
have	0
a	0
GAP43	0
-	0
ir	0
band	0
in	0
the	0
IML	0
,	0
similar	0
to	0
that	0
of	0
controls	0
,	0
reinforces	0
prior	0
data	0
on	0
the	0
blockade	0
of	0
MFS	0
in	0
these	0
animals	0
.	0

The	0
change	0
in	0
GAP43	0
-	0
ir	0
present	0
in	0
Pilo	1
-	0
treated	0
animals	0
was	0
a	0
thinning	0
of	0
the	0
band	0
to	0
a	0
very	0
narrow	0
layer	0
just	0
above	0
the	0
granule	0
cell	0
layer	0
that	0
is	0
likely	0
to	0
be	0
associated	0
with	0
the	0
loss	0
of	0
hilar	0
cell	0
projections	0
that	0
express	0
GAP	0
-	0
43	0
.	0

Nicotine	1
antagonizes	0
caffeine	1
-	0
but	0
not	0
pentylenetetrazole	1
-	0
induced	0
anxiogenic	0
effect	0
in	0
mice	0
.	0

RATI0NALE	0
:	0
Nicotine	1
and	0
caffeine	1
are	0
widely	0
consumed	0
licit	0
psychoactive	0
drugs	0
worldwide	0
.	0

Epidemiological	0
studies	0
showed	0
that	0
they	0
were	0
generally	0
used	0
concurrently	0
.	0

Although	0
some	0
studies	0
in	0
experimental	0
animals	0
indicate	0
clear	0
pharmacological	0
interactions	0
between	0
them	0
,	0
no	0
studies	0
have	0
shown	0
a	0
specific	0
interaction	0
on	0
anxiety	3
responses	0
.	0

0BJECTIVES	0
:	0
The	0
present	0
study	0
investigates	0
the	0
effects	0
of	0
nicotine	1
on	0
anxiety	3
induced	0
by	0
caffeine	1
and	0
another	0
anxiogenic	0
drug	0
,	0
pentylenetetrazole	1
,	0
in	0
mice	0
.	0

The	0
elevated	0
plus	0
-	0
maze	0
(	0
EPM	0
)	0
test	0
was	0
used	0
to	0
evaluate	0
the	0
effects	0
of	0
drugs	0
on	0
anxiety	3
.	0

METH0DS	0
:	0
Adult	0
male	0
Swiss	0
Webster	0
mice	0
(	0
25	0
-	0
32	0
g	0
)	0
were	0
given	0
nicotine	1
(	0
0	0
.	0
05	0
-	0
0	0
.	0
25	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
or	0
saline	0
10	0
min	0
before	0
caffeine	1
(	0
70	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
or	0
pentylenetetrazole	1
(	0
15	0
and	0
30	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
injections	0
.	0

After	0
15	0
min	0
,	0
mice	0
were	0
evaluated	0
for	0
their	0
open	0
-	0
and	0
closed	0
-	0
arm	0
time	0
and	0
entries	0
on	0
the	0
EPM	0
for	0
a	0
10	0
-	0
min	0
session	0
.	0

Locomotor	0
activity	0
was	0
recorded	0
for	0
individual	0
groups	0
by	0
using	0
the	0
same	0
treatment	0
protocol	0
with	0
the	0
EPM	0
test	0
.	0

RESULTS	0
:	0
Nicotine	1
(	0
0	0
.	0
05	0
-	0
0	0
.	0
25	0
mg	0
/	0
kg	0
)	0
itself	0
did	0
not	0
produce	0
any	0
significant	0
effect	0
in	0
the	0
EPM	0
test	0
,	0
whereas	0
caffeine	1
(	0
70	0
mg	0
/	0
kg	0
)	0
and	0
pentylenetetrazole	1
(	0
30	0
mg	0
/	0
kg	0
)	0
produced	0
an	0
anxiogenic	0
effect	0
,	0
apparent	0
with	0
decreases	0
in	0
open	0
-	0
arm	0
time	0
and	0
entry	0
.	0

Nicotine	1
(	0
0	0
.	0
25	0
mg	0
/	0
kg	0
)	0
pretreatment	0
blocked	0
the	0
caffeine	1
-	0
but	0
not	0
pentylenetetrazole	1
-	0
induced	0
anxiety	3
.	0

Administration	0
of	0
each	0
drug	0
and	0
their	0
combinations	0
did	0
not	0
produce	0
any	0
effect	0
on	0
locomotor	0
activity	0
.	0

C0NCLUSI0NS	0
:	0
0ur	0
results	0
suggest	0
that	0
the	0
antagonistic	0
effect	0
of	0
nicotine	1
on	0
caffeine	1
-	0
induced	0
anxiety	3
is	0
specific	0
to	0
caffeine	1
,	0
instead	0
of	0
a	0
non	0
-	0
specific	0
anxiolytic	0
effect	0
.	0

Thus	0
,	0
it	0
may	0
extend	0
the	0
current	0
findings	0
on	0
the	0
interaction	0
between	0
nicotine	1
and	0
caffeine	1
.	0

Long	0
term	0
hormone	0
therapy	0
for	0
perimenopausal	0
and	0
postmenopausal	0
women	0
.	0

BACKGR0UND	0
:	0
Hormone	0
therapy	0
(	0
HT	0
)	0
is	0
widely	0
used	0
for	0
controlling	0
menopausal	3
symptoms	4
.	0

It	0
has	0
also	0
been	0
used	0
for	0
the	0
management	0
and	0
prevention	0
of	0
cardiovascular	3
disease	4
,	0
osteoporosis	3
and	0
dementia	3
in	0
older	0
women	0
but	0
the	0
evidence	0
supporting	0
its	0
use	0
for	0
these	0
indications	0
is	0
largely	0
observational	0
.	0

0BJECTIVES	0
:	0
To	0
assess	0
the	0
effect	0
of	0
long	0
-	0
term	0
HT	0
on	0
mortality	0
,	0
heart	3
disease	4
,	0
venous	3
thromboembolism	4
,	0
stroke	3
,	0
transient	3
ischaemic	4
attacks	4
,	0
breast	3
cancer	4
,	0
colorectal	3
cancer	4
,	0
ovarian	3
cancer	4
,	0
endometrial	3
cancer	4
,	0
gallbladder	3
disease	4
,	0
cognitive	0
function	0
,	0
dementia	3
,	0
fractures	3
and	0
quality	0
of	0
life	0
.	0

SEARCH	0
STRATEGY	0
:	0
We	0
searched	0
the	0
following	0
databases	0
up	0
to	0
November	0
2004	0
:	0
the	0
Cochrane	0
Menstrual	0
Disorders	0
and	0
Subfertility	0
Group	0
Trials	0
Register	0
,	0
Cochrane	0
Central	0
Register	0
of	0
Controlled	0
Trials	0
(	0
CENTRAL	0
)	0
,	0
MEDLINE	0
,	0
EMBASE	0
,	0
Biological	0
Abstracts	0
.	0

Relevant	0
non	0
-	0
indexed	0
journals	0
and	0
conference	0
abstracts	0
were	0
also	0
searched	0
.	0

SELECTI0N	0
CRITERIA	0
:	0
Randomised	0
double	0
-	0
blind	0
trials	0
of	0
HT	0
(	0
oestrogens	1
with	0
or	0
without	0
progestogens	1
)	0
versus	0
placebo	0
,	0
taken	0
for	0
at	0
least	0
one	0
year	0
by	0
perimenopausal	0
or	0
postmenopausal	0
women	0
.	0

DATA	0
C0LLECTI0N	0
AND	0
ANALYSIS	0
:	0
Fifteen	0
RCTs	0
were	0
included	0
.	0

Trials	0
were	0
assessed	0
for	0
quality	0
and	0
two	0
review	0
authors	0
extracted	0
data	0
independently	0
.	0

They	0
calculated	0
risk	0
ratios	0
for	0
dichotomous	0
outcomes	0
and	0
weighted	0
mean	0
differences	0
for	0
continuous	0
outcomes	0
.	0

Clinical	0
heterogeneity	0
precluded	0
meta	0
-	0
analysis	0
for	0
most	0
outcomes	0
.	0

MAIN	0
RESULTS	0
:	0
All	0
the	0
statistically	0
significant	0
results	0
were	0
derived	0
from	0
the	0
two	0
biggest	0
trials	0
.	0

In	0
relatively	0
healthy	0
women	0
,	0
combined	0
continuous	0
HT	0
significantly	0
increased	0
the	0
risk	0
of	0
venous	3
thromboembolism	4
or	0
coronary	0
event	0
(	0
after	0
one	0
year	0
'	0
s	0
use	0
)	0
,	0
stroke	3
(	0
after	0
3	0
years	0
)	0
,	0
breast	3
cancer	4
(	0
after	0
5	0
years	0
)	0
and	0
gallbladder	3
disease	4
.	0

Long	0
-	0
term	0
oestrogen	1
-	0
only	0
HT	0
also	0
significantly	0
increased	0
the	0
risk	0
of	0
stroke	3
and	0
gallbladder	3
disease	4
.	0

0verall	0
,	0
the	0
only	0
statistically	0
significant	0
benefits	0
of	0
HT	0
were	0
a	0
decreased	0
incidence	0
of	0
fractures	3
and	0
colon	3
cancer	4
with	0
long	0
-	0
term	0
use	0
.	0

Among	0
relatively	0
healthy	0
women	0
over	0
65	0
years	0
taking	0
continuous	0
combined	0
HT	0
,	0
there	0
was	0
a	0
statistically	0
significant	0
increase	0
in	0
the	0
incidence	0
of	0
dementia	3
.	0

Among	0
women	0
with	0
cardiovascular	3
disease	4
,	0
long	0
-	0
term	0
use	0
of	0
combined	0
continuous	0
HT	0
significantly	0
increased	0
the	0
risk	0
of	0
venous	3
thromboembolism	4
.	0

No	0
trials	0
focussed	0
specifically	0
on	0
younger	0
women	0
.	0

However	0
,	0
one	0
trial	0
analysed	0
subgroups	0
of	0
2839	0
relatively	0
healthy	0
50	0
to	0
59	0
year	0
-	0
old	0
women	0
taking	0
combined	0
continuous	0
HT	0
and	0
1637	0
taking	0
oestrogen	1
-	0
only	0
HT	0
,	0
versus	0
similar	0
-	0
sized	0
placebo	0
groups	0
.	0

The	0
only	0
significantly	0
increased	0
risk	0
reported	0
was	0
for	0
venous	3
thromboembolism	4
in	0
women	0
taking	0
combined	0
continuous	0
HT	0
;	0
their	0
absolute	0
risk	0
remained	0
very	0
low	0
.	0

AUTH0RS	0
'	0
C0NCLUSI0NS	0
:	0
HT	0
is	0
not	0
indicated	0
for	0
the	0
routine	0
management	0
of	0
chronic	3
disease	4
.	0

We	0
need	0
more	0
evidence	0
on	0
the	0
safety	0
of	0
HT	0
for	0
menopausal	0
symptom	0
control	0
,	0
though	0
short	0
-	0
term	0
use	0
appears	0
to	0
be	0
relatively	0
safe	0
for	0
healthy	0
younger	0
women	0
.	0

Drug	3
-	4
induced	4
liver	4
injury	4
:	0
an	0
analysis	0
of	0
461	0
incidences	0
submitted	0
to	0
the	0
Spanish	0
registry	0
over	0
a	0
10	0
-	0
year	0
period	0
.	0

BACKGR0UND	0
&	0
AIMS	0
:	0
Progress	0
in	0
the	0
understanding	0
of	0
susceptibility	0
factors	0
to	0
drug	3
-	4
induced	4
liver	4
injury	4
(	0
DILI	3
)	0
and	0
outcome	0
predictability	0
are	0
hampered	0
by	0
the	0
lack	0
of	0
systematic	0
programs	0
to	0
detect	0
bona	0
fide	0
cases	0
.	0

METH0DS	0
:	0
A	0
cooperative	0
network	0
was	0
created	0
in	0
1994	0
in	0
Spain	0
to	0
identify	0
all	0
suspicions	0
of	0
DILI	3
following	0
a	0
prospective	0
structured	0
report	0
form	0
.	0

The	0
liver	3
damage	4
was	0
characterized	0
according	0
to	0
hepatocellular	0
,	0
cholestatic	3
,	0
and	0
mixed	0
laboratory	0
criteria	0
and	0
to	0
histologic	0
criteria	0
when	0
available	0
.	0

Further	0
evaluation	0
of	0
causality	0
assessment	0
was	0
centrally	0
performed	0
.	0

RESULTS	0
:	0
Since	0
April	0
1994	0
to	0
August	0
2004	0
,	0
461	0
out	0
of	0
570	0
submitted	0
cases	0
,	0
involving	0
505	0
drugs	0
,	0
were	0
deemed	0
to	0
be	0
related	0
to	0
DILI	3
.	0

The	0
antiinfective	0
group	0
of	0
drugs	0
was	0
the	0
more	0
frequently	0
incriminated	0
,	0
amoxicillin	1
-	2
clavulanate	2
accounting	0
for	0
the	0
12	0
.	0
8	0
%	0
of	0
the	0
whole	0
series	0
.	0

The	0
hepatocellular	0
pattern	0
of	0
damage	0
was	0
the	0
most	0
common	0
(	0
58	0
%	0
)	0
,	0
was	0
inversely	0
correlated	0
with	0
age	0
(	0
P	0
<	0
.	0
0001	0
)	0
,	0
and	0
had	0
the	0
worst	0
outcome	0
(	0
Cox	0
regression	0
,	0
P	0
<	0
.	0
034	0
)	0
.	0

Indeed	0
,	0
the	0
incidence	0
of	0
liver	0
transplantation	0
and	0
death	0
in	0
this	0
group	0
was	0
11	0
.	0
7	0
%	0
if	0
patients	0
had	0
jaundice	3
at	0
presentation	0
,	0
whereas	0
the	0
corresponding	0
figure	0
was	0
3	0
.	0
8	0
%	0
in	0
nonjaundiced	0
patients	0
(	0
P	0
<	0
.	0
04	0
)	0
.	0

Factors	0
associated	0
with	0
the	0
development	0
of	0
fulminant	3
hepatic	4
failure	4
were	0
female	0
sex	0
(	0
0R	0
=	0
25	0
;	0
95	0
%	0
CI	0
:	0
4	0
.	0
1	0
-	0
151	0
;	0
P	0
<	0
.	0
0001	0
)	0
,	0
hepatocellular	0
damage	0
(	0
0R	0
=	0
7	0
.	0
9	0
;	0
95	0
%	0
CI	0
:	0
1	0
.	0
6	0
-	0
37	0
;	0
P	0
<	0
.	0
009	0
)	0
,	0
and	0
higher	0
baseline	0
plasma	0
bilirubin	1
value	0
(	0
0R	0
=	0
1	0
.	0
15	0
;	0
95	0
%	0
CI	0
:	0
1	0
.	0
09	0
-	0
1	0
.	0
22	0
;	0
P	0
<	0
.	0
0001	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Patients	0
with	0
drug	0
-	0
induced	0
hepatocellular	0
jaundice	3
have	0
11	0
.	0
7	0
%	0
chance	0
of	0
progressing	0
to	0
death	0
or	0
transplantation	0
.	0

Amoxicillin	1
-	2
clavulanate	2
stands	0
out	0
as	0
the	0
most	0
common	0
drug	0
related	0
to	0
DILI	3
.	0

Morphological	0
evaluation	0
of	0
the	0
effect	0
of	0
d	1
-	2
ribose	2
on	0
adriamycin	1
-	0
evoked	0
cardiotoxicity	3
in	0
rats	0
.	0

The	0
influence	0
of	0
d	1
-	2
ribose	2
on	0
adriamycin	1
-	0
induced	0
myocardiopathy	3
in	0
rats	0
was	0
studied	0
.	0

Adriamycin	1
in	0
the	0
cumulative	0
dose	0
of	0
25	0
mg	0
/	0
kg	0
evoked	0
fully	0
developed	0
cardiac	3
toxicity	4
.	0

D	1
-	2
ribose	2
in	0
the	0
multiple	0
doses	0
of	0
200	0
mg	0
/	0
kg	0
did	0
not	0
influence	0
ADR	1
cardiotoxicity	3
.	0

In	0
vivo	0
evidences	0
suggesting	0
the	0
role	0
of	0
oxidative	0
stress	0
in	0
pathogenesis	0
of	0
vancomycin	1
-	0
induced	0
nephrotoxicity	3
:	0
protection	0
by	0
erdosteine	1
.	0

The	0
aims	0
of	0
this	0
study	0
were	0
to	0
examine	0
vancomycin	1
(	0
VCM	1
)	0
-	0
induced	0
oxidative	0
stress	0
that	0
promotes	0
production	0
of	0
reactive	0
oxygen	1
species	0
(	0
R0S	0
)	0
and	0
to	0
investigate	0
the	0
role	0
of	0
erdosteine	1
,	0
an	0
expectorant	0
agent	0
,	0
which	0
has	0
also	0
antioxidant	0
properties	0
,	0
on	0
kidney	0
tissue	0
against	0
the	0
possible	0
VCM	1
-	0
induced	0
renal	3
impairment	4
in	0
rats	0
.	0

Rats	0
were	0
divided	0
into	0
three	0
groups	0
:	0
sham	0
,	0
VCM	1
and	0
VCM	1
plus	0
erdosteine	1
.	0

VCM	1
was	0
administrated	0
intraperitoneally	0
(	0
i	0
.	0
p	0
.	0
)	0
with	0
200mgkg	0
(	0
-	0
1	0
)	0
twice	0
daily	0
for	0
7	0
days	0
.	0

Erdosteine	1
was	0
administered	0
orally	0
.	0

VCM	1
administration	0
to	0
control	0
rats	0
significantly	0
increased	0
renal	0
malondialdehyde	1
(	0
MDA	1
)	0
and	0
urinary	0
N	0
-	0
acetyl	0
-	0
beta	0
-	0
d	0
-	0
glucosaminidase	0
(	0
NAG	0
,	0
a	0
marker	0
of	0
renal	3
tubular	4
injury	4
)	0
excretion	0
but	0
decreased	0
superoxide	1
dismutase	0
(	0
S0D	0
)	0
and	0
catalase	0
(	0
CAT	0
)	0
activities	0
.	0

Erdosteine	1
administration	0
with	0
VCM	1
injections	0
caused	0
significantly	0
decreased	0
renal	0
MDA	1
and	0
urinary	0
NAG	0
excretion	0
,	0
and	0
increased	0
S0D	0
activity	0
,	0
but	0
not	0
CAT	0
activity	0
in	0
renal	0
tissue	0
when	0
compared	0
with	0
VCM	1
alone	0
.	0

Erdosteine	1
showed	0
histopathological	0
protection	0
against	0
VCM	1
-	0
induced	0
nephrotoxicity	3
.	0

There	0
were	0
a	0
significant	0
dilatation	0
of	0
tubular	0
lumens	0
,	0
extensive	0
epithelial	0
cell	0
vacuolization	0
,	0
atrophy	3
,	0
desquamation	3
,	0
and	0
necrosis	3
in	0
VCM	1
-	0
treated	0
rats	0
more	0
than	0
those	0
of	0
the	0
control	0
and	0
the	0
erdosteine	1
groups	0
.	0

Erdosteine	1
caused	0
a	0
marked	0
reduction	0
in	0
the	0
extent	0
of	0
tubular	0
damage	0
.	0

It	0
is	0
concluded	0
that	0
oxidative	0
tubular	0
damage	0
plays	0
an	0
important	0
role	0
in	0
the	0
VCM	1
-	0
induced	0
nephrotoxicity	3
and	0
the	0
modulation	0
of	0
oxidative	0
stress	0
with	0
erdosteine	1
reduces	0
the	0
VCM	1
-	0
induced	0
kidney	3
damage	4
both	0
at	0
the	0
biochemical	0
and	0
histological	0
levels	0
.	0

Gemfibrozil	1
-	0
lovastatin	1
therapy	0
for	0
primary	0
hyperlipoproteinemias	3
.	0

The	0
specific	0
aim	0
of	0
this	0
retrospective	0
,	0
observational	0
study	0
was	0
to	0
assess	0
safety	0
and	0
efficacy	0
of	0
long	0
-	0
term	0
(	0
21	0
months	0
/	0
patient	0
)	0
,	0
open	0
-	0
label	0
,	0
gemfibrozil	1
-	0
lovastatin	1
treatment	0
in	0
80	0
patients	0
with	0
primary	0
mixed	0
hyperlipidemia	3
(	0
68	0
%	0
of	0
whom	0
had	0
atherosclerotic	3
vascular	4
disease	4
)	0
.	0

Because	0
ideal	0
lipid	0
targets	0
were	0
not	0
reached	0
(	0
low	0
-	0
density	0
lipoprotein	0
(	0
LDL	0
)	0
cholesterol	1
less	0
than	0
130	0
mg	0
/	0
dl	0
,	0
high	0
-	0
density	0
lipoprotein	0
(	0
HDL	0
)	0
cholesterol	1
greater	0
than	0
35	0
mg	0
/	0
dl	0
,	0
or	0
total	0
cholesterol	1
/	0
HDL	0
cholesterol	1
less	0
than	0
4	0
.	0
5	0
mg	0
/	0
dl	0
)	0
with	0
diet	0
plus	0
a	0
single	0
drug	0
,	0
gemfibrozil	1
(	0
1	0
.	0
2	0
g	0
/	0
day	0
)	0
-	0
lovastatin	1
(	0
primarily	0
20	0
or	0
40	0
mg	0
)	0
treatment	0
was	0
given	0
.	0

Follow	0
-	0
up	0
visits	0
were	0
scheduled	0
with	0
2	0
-	0
drug	0
therapy	0
every	0
6	0
to	0
8	0
weeks	0
,	0
an	0
average	0
of	0
10	0
.	0
3	0
visits	0
per	0
patient	0
,	0
with	0
741	0
batteries	0
of	0
6	0
liver	0
function	0
tests	0
and	0
714	0
creatine	1
phosphokinase	0
levels	0
measured	0
.	0

0nly	0
1	0
of	0
the	0
4	0
,	0
446	0
liver	0
function	0
tests	0
(	0
0	0
.	0
02	0
%	0
)	0
,	0
a	0
gamma	0
glutamyl	0
transferase	0
,	0
was	0
greater	0
than	0
or	0
equal	0
to	0
3	0
times	0
the	0
upper	0
normal	0
limit	0
.	0

0f	0
the	0
714	0
creatine	1
phosphokinase	0
levels	0
,	0
9	0
%	0
were	0
high	0
;	0
only	0
1	0
(	0
0	0
.	0
1	0
%	0
)	0
was	0
greater	0
than	0
or	0
equal	0
to	0
3	0
times	0
the	0
upper	0
normal	0
limit	0
.	0

With	0
2	0
-	0
drug	0
therapy	0
,	0
mean	0
total	0
cholesterol	1
decreased	0
22	0
%	0
from	0
255	0
to	0
200	0
mg	0
/	0
dl	0
,	0
triglyceride	1
levels	0
decreased	0
35	0
%	0
from	0
236	0
to	0
154	0
mg	0
/	0
dl	0
,	0
LDL	0
cholesterol	1
decreased	0
26	0
%	0
from	0
176	0
to	0
131	0
mg	0
/	0
dl	0
,	0
and	0
the	0
total	0
cholesterol	1
/	0
HDL	0
cholesterol	1
ratio	0
decreased	0
24	0
%	0
from	0
7	0
.	0
1	0
to	0
5	0
.	0
4	0
,	0
all	0
p	0
less	0
than	0
or	0
equal	0
to	0
0	0
.	0
0001	0
.	0

Myositis	3
,	0
attributable	0
to	0
the	0
drug	0
combination	0
and	0
symptomatic	0
enough	0
to	0
discontinue	0
it	0
,	0
occurred	0
in	0
3	0
%	0
of	0
patients	0
,	0
and	0
in	0
1	0
%	0
with	0
concurrent	0
high	0
creatine	1
phosphokinase	0
(	0
769	0
U	0
/	0
liter	0
)	0
;	0
no	0
patients	0
had	0
rhabdomyolysis	3
or	0
myoglobinuria	3
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Does	0
domperidone	1
potentiate	0
mirtazapine	1
-	0
associated	0
restless	3
legs	4
syndrome	4
?	0

There	0
is	0
now	0
evidence	0
to	0
suggest	0
a	0
central	0
role	0
for	0
the	0
dopaminergic	0
system	0
in	0
restless	3
legs	4
syndrome	4
(	0
RLS	3
)	0
.	0

For	0
example	0
,	0
the	0
symptoms	0
of	0
RLS	3
can	0
be	0
dramatically	0
improved	0
by	0
levodopa	1
and	0
dopamine	1
agonists	0
,	0
whereas	0
central	0
dopamine	1
D2	0
receptor	0
antagonists	0
can	0
induce	0
or	0
aggravate	0
RLS	3
symptoms	0
.	0

To	0
our	0
knowledge	0
,	0
there	0
is	0
no	0
previous	0
report	0
regarding	0
whether	0
domperidone	1
,	0
a	0
peripheral	0
dopamine	1
D2	0
receptor	0
antagonist	0
,	0
can	0
also	0
induce	0
or	0
aggravate	0
symptoms	0
of	0
RLS	3
.	0

Mirtazapine	1
,	0
the	0
first	0
noradrenergic	0
and	0
specific	0
serotonergic	0
antidepressant	0
(	0
NaSSA	0
)	0
,	0
has	0
been	0
associated	0
with	0
RLS	3
in	0
several	0
recent	0
publications	0
.	0

The	0
authors	0
report	0
here	0
a	0
depressed	0
patient	0
comorbid	0
with	0
postprandial	3
dyspepsia	4
who	0
developed	0
RLS	3
after	0
mirtazapine	1
had	0
been	0
added	0
to	0
his	0
domperidone	1
therapy	0
.	0

0ur	0
patient	0
started	0
to	0
have	0
symptoms	0
of	0
RLS	3
only	0
after	0
he	0
had	0
been	0
treated	0
with	0
mirtazapine	1
,	0
and	0
his	0
RLS	3
symptoms	0
resolved	0
completely	0
upon	0
discontinuation	0
of	0
his	0
mirtazapine	1
.	0

Such	0
a	0
temporal	0
relationship	0
between	0
the	0
use	0
of	0
mirtazapine	1
and	0
the	0
symptoms	0
of	0
RLS	3
in	0
our	0
patient	0
did	0
not	0
support	0
a	0
potentiating	0
effect	0
of	0
domperione	1
on	0
mirtazapine	1
-	0
associated	0
RLS	3
.	0

However	0
,	0
physicians	0
should	0
be	0
aware	0
of	0
the	0
possibility	0
that	0
mirtazapine	1
can	0
be	0
associated	0
with	0
RLS	3
in	0
some	0
individuals	0
,	0
especially	0
those	0
receiving	0
concomitant	0
dopamine	1
D2	0
receptor	0
antagonists	0
.	0

Antiandrogenic	0
therapy	0
can	0
cause	0
coronary	3
arterial	4
disease	4
.	0

AIM	0
:	0
To	0
study	0
the	0
change	0
of	0
lipid	0
metabolism	0
by	0
antiandrogen	0
therapy	0
in	0
patients	0
with	0
prostate	3
cancer	4
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
We	0
studied	0
with	0
a	0
2	0
.	0
5	0
years	0
follow	0
-	0
up	0
the	0
changes	0
in	0
plasma	0
cholesterols	1
(	0
C	1
)	0
,	0
triglycerides	1
(	0
TG	1
)	0
,	0
lipoproteins	0
(	0
LP	0
)	0
,	0
and	0
apolipoproteins	0
(	0
Apo	0
)	0
B	0
-	0
100	0
,	0
A	0
-	0
I	0
,	0
and	0
A	0
-	0
II	0
pro	0
fi	0
les	0
in	0
24	0
patients	0
of	0
mean	0
age	0
60	0
years	0
with	0
low	0
risk	0
prostate	3
cancer	4
(	0
stage	0
:	0
T1cN0M0	0
,	0
Gleason	0
score	0
:	0
2	0
-	0
5	0
)	0
during	0
treatment	0
with	0
cyproterone	1
acetate	2
(	0
CPA	1
)	0
without	0
surgical	0
management	0
or	0
radiation	0
therapy	0
.	0

RESULTS	0
:	0
Significant	0
decreases	0
of	0
HDL	0
-	0
C	0
,	0
Apo	0
A	0
-	0
I	0
and	0
Apo	0
A	0
-	0
II	0
and	0
an	0
increase	0
of	0
triglyceride	1
levels	0
in	0
VLDL	0
were	0
induced	0
by	0
CPA	1
.	0

After	0
a	0
period	0
of	0
2	0
.	0
5	0
years	0
on	0
CPA	1
treatment	0
,	0
four	0
patients	0
out	0
of	0
twenty	0
-	0
four	0
were	0
found	0
to	0
be	0
affected	0
by	0
coronary	3
heart	4
disease	4
.	0

C0NCLUSI0NS	0
:	0
Ischaemic	0
coronary	3
arteriosclerosis	4
with	0
an	0
incidence	0
rate	0
of	0
16	0
.	0
6	0
%	0
as	0
caused	0
by	0
prolonged	0
CPA	1
therapy	0
is	0
mediated	0
through	0
changes	0
in	0
HDL	0
cholesterol	1
,	0
Apo	0
A	0
-	0
I	0
and	0
Apo	0
A	0
-	0
II	0
pro	0
fi	0
les	0
,	0
other	0
than	0
the	0
well	0
-	0
known	0
hyperglyceridemic	3
effect	4
caused	0
by	0
estrogen	1
.	0

5	1
-	2
Fluorouracil	2
cardiotoxicity	3
induced	0
by	0
alpha	1
-	2
fluoro	2
-	2
beta	2
-	2
alanine	2
.	0

Cardiotoxicity	3
is	0
a	0
rare	0
complication	0
occurring	0
during	0
5	1
-	2
fluorouracil	2
(	0
5	1
-	2
FU	2
)	0
treatment	0
for	0
malignancies	3
.	0

We	0
herein	0
report	0
the	0
case	0
of	0
a	0
70	0
-	0
year	0
-	0
old	0
man	0
with	0
5	1
-	2
FU	2
-	0
induced	0
cardiotoxicity	3
,	0
in	0
whom	0
a	0
high	0
serum	0
level	0
of	0
alpha	1
-	2
fluoro	2
-	2
beta	2
-	2
alanine	2
(	0
FBAL	1
)	0
was	0
observed	0
.	0

The	0
patient	0
,	0
who	0
had	0
unresectable	0
colon	3
cancer	4
metastases	0
to	0
the	0
liver	0
and	0
lung	0
,	0
was	0
referred	0
to	0
us	0
for	0
chemotherapy	0
from	0
an	0
affiliated	0
hospital	0
;	0
he	0
had	0
no	0
cardiac	0
history	0
.	0

After	0
admission	0
,	0
the	0
patient	0
received	0
a	0
continuous	0
intravenous	0
infusion	0
of	0
5	1
-	2
FU	2
(	0
1000	0
mg	0
/	0
day	0
)	0
,	0
during	0
which	0
precordial	3
pain	4
with	0
right	3
bundle	4
branch	4
block	4
occurred	0
concomitantly	0
with	0
a	0
high	0
serum	0
FBAL	1
concentration	0
of	0
1955	0
ng	0
/	0
ml	0
.	0

Both	0
the	0
precordial	3
pain	4
and	0
the	0
electrocardiographic	0
changes	0
disappeared	0
spontaneously	0
after	0
the	0
discontinuation	0
of	0
5	1
-	2
FU	2
.	0

As	0
the	0
precordial	3
pain	4
in	0
this	0
patient	0
was	0
considered	0
to	0
have	0
been	0
due	0
to	0
5	1
-	2
FU	2
-	0
induced	0
cardiotoxicity	3
,	0
the	0
administration	0
of	0
5	1
-	2
FU	2
was	0
abandoned	0
.	0

Instead	0
,	0
oral	0
administration	0
of	0
S	0
-	0
1	0
(	0
a	0
derivative	0
of	0
5	1
-	2
FU	2
)	0
,	0
at	0
200	0
mg	0
/	0
day	0
twice	0
a	0
week	0
,	0
was	0
instituted	0
,	0
because	0
S	0
-	0
1	0
has	0
a	0
strong	0
inhibitory	0
effect	0
on	0
dihydropyrimidine	1
dehydrogenase	0
,	0
which	0
catalyzes	0
the	0
degradative	0
of	0
5	1
-	2
FU	2
into	0
FBAL	1
.	0

The	0
serum	0
FBAL	1
concentration	0
subsequently	0
decreased	0
to	0
352	0
ng	0
/	0
ml	0
,	0
the	0
same	0
as	0
the	0
value	0
measured	0
on	0
the	0
first	0
day	0
of	0
S	0
-	0
1	0
administration	0
.	0

Thereafter	0
,	0
no	0
cardiac	3
symptoms	4
were	0
observed	0
.	0

The	0
patient	0
achieved	0
a	0
partial	0
response	0
6	0
months	0
after	0
the	0
initiation	0
of	0
the	0
S	0
-	0
1	0
treatment	0
.	0

The	0
experience	0
of	0
this	0
case	0
,	0
together	0
with	0
a	0
review	0
of	0
the	0
literature	0
,	0
suggests	0
that	0
FBAL	1
is	0
related	0
to	0
5	1
-	2
FU	2
-	0
induced	0
cardiotoxicity	3
.	0

S	0
-	0
1	0
may	0
be	0
administered	0
safely	0
to	0
patients	0
with	0
5	1
-	2
FU	2
-	0
induced	0
cardiotoxicity	3
.	0

Hepatocellular	3
carcinoma	4
in	0
Fanconi	3
'	4
s	4
anemia	4
treated	0
with	0
androgen	1
and	0
corticosteroid	1
.	0

The	0
case	0
of	0
an	0
11	0
-	0
year	0
-	0
old	0
boy	0
is	0
reported	0
who	0
was	0
known	0
to	0
have	0
Fanconi	3
'	4
s	4
anemia	4
for	0
3	0
years	0
and	0
was	0
treated	0
with	0
androgens	1
,	0
corticosteroids	1
and	0
transfusions	0
.	0

Two	0
weeks	0
before	0
his	0
death	0
he	0
was	0
readmitted	0
because	0
of	0
aplastic	0
crisis	0
with	0
septicemia	3
and	0
marked	0
abnormalities	0
in	0
liver	0
function	0
and	0
died	0
of	0
hemorrhagic	3
bronchopneumonia	4
.	0

At	0
autopsy	0
peliosis	3
and	0
multiple	0
hepatic	3
tumors	4
were	0
found	0
which	0
histologically	0
proved	0
to	0
be	0
well	0
-	0
differentiated	0
hepatocellular	3
carcinoma	4
.	0

This	0
case	0
contributes	0
to	0
the	0
previous	0
observations	0
that	0
non	0
-	0
metastasizing	0
hepatic	3
neoplasms	4
and	0
peliosis	3
can	0
develop	0
in	0
patients	0
with	0
androgen	1
-	0
and	0
corticosteroid	1
-	0
treated	0
Fanconi	3
'	4
s	4
anemia	4
.	0

The	0
influence	0
of	0
the	0
time	0
interval	0
between	0
monoHER	1
and	0
doxorubicin	1
administration	0
on	0
the	0
protection	0
against	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
in	0
mice	0
.	0

PURP0SE	0
:	0
Despite	0
its	0
well	0
-	0
known	0
cardiotoxicity	3
,	0
the	0
anthracyclin	0
doxorubicin	1
(	0
D0X	1
)	0
continues	0
to	0
be	0
an	0
effective	0
and	0
widely	0
used	0
chemotherapeutic	0
agent	0
.	0

D0X	1
-	0
induced	0
cardiac	3
damage	4
presumably	0
results	0
from	0
the	0
formation	0
of	0
free	0
radicals	0
by	0
D0X	1
.	0

Reactive	0
oxygen	1
species	0
particularly	0
affect	0
the	0
cardiac	0
myocytes	0
because	0
these	0
cells	0
seem	0
to	0
have	0
a	0
relatively	0
poor	0
antioxidant	0
defense	0
system	0
.	0

The	0
semisynthetic	0
flavonoid	1
monohydroxyethylrutoside	1
(	0
monoHER	1
)	0
showed	0
cardioprotection	0
against	0
D0X	1
-	0
induced	0
cardiotoxicity	3
through	0
its	0
radical	0
scavenging	0
and	0
iron	1
chelating	0
properties	0
.	0

Because	0
of	0
the	0
relatively	0
short	0
final	0
half	0
-	0
life	0
of	0
monoHER	1
(	0
about	0
30	0
min	0
)	0
,	0
it	0
is	0
expected	0
that	0
the	0
time	0
interval	0
between	0
monoHER	1
and	0
D0X	1
might	0
be	0
of	0
influence	0
on	0
the	0
cardioprotective	0
effect	0
of	0
monoHER	1
.	0

Therefore	0
,	0
the	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
investigate	0
this	0
possible	0
effect	0
.	0

METH0DS	0
:	0
Six	0
groups	0
of	0
6	0
BALB	0
/	0
c	0
mice	0
were	0
treated	0
with	0
saline	0
,	0
D0X	1
alone	0
or	0
D0X	1
(	0
4	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
preceded	0
by	0
monoHER	1
(	0
500	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
with	0
an	0
interval	0
of	0
10	0
,	0
30	0
,	0
60	0
or	0
120	0
min	0
.	0

After	0
a	0
6	0
-	0
week	0
treatment	0
period	0
and	0
additional	0
observation	0
for	0
2	0
weeks	0
,	0
the	0
mice	0
were	0
sacrificed	0
.	0

Their	0
cardiac	0
tissues	0
were	0
processed	0
for	0
light	0
microscopy	0
,	0
after	0
which	0
cardiomyocyte	3
damage	4
was	0
evaluated	0
according	0
to	0
Billingham	0
(	0
in	0
Cancer	3
Treat	0
Rep	0
62	0
(	0
6	0
)	0
:	0
865	0
-	0
872	0
,	0
1978	0
)	0
.	0

Microscopic	0
evaluation	0
revealed	0
that	0
treatment	0
with	0
D0X	1
alone	0
induced	0
significant	0
cardiac	3
damage	4
in	0
comparison	0
to	0
the	0
saline	0
control	0
group	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

RESULTS	0
:	0
The	0
number	0
of	0
damaged	0
cardiomyocytes	0
was	0
9	0
.	0
6	0
-	0
fold	0
(	0
95	0
%	0
CI	0
4	0
.	0
4	0
-	0
21	0
.	0
0	0
)	0
higher	0
in	0
mice	0
treated	0
with	0
D0X	1
alone	0
than	0
that	0
in	0
animals	0
of	0
the	0
control	0
group	0
.	0

The	0
ratio	0
of	0
aberrant	0
cardiomyocytes	0
in	0
mice	0
treated	0
with	0
D0X	1
preceded	0
by	0
monoHER	1
and	0
those	0
in	0
mice	0
treated	0
with	0
saline	0
ranged	0
from	0
1	0
.	0
6	0
to	0
2	0
.	0
8	0
(	0
mean	0
2	0
.	0
2	0
,	0
95	0
%	0
CI	0
1	0
.	0
2	0
-	0
4	0
.	0
1	0
,	0
P	0
=	0
0	0
.	0
019	0
)	0
.	0

The	0
mean	0
protective	0
effect	0
by	0
adding	0
monoHER	1
before	0
D0X	1
led	0
to	0
a	0
significant	0
4	0
.	0
4	0
-	0
fold	0
reduction	0
(	0
P	0
<	0
0	0
.	0
001	0
,	0
95	0
%	0
CI	0
2	0
.	0
3	0
-	0
8	0
.	0
2	0
)	0
of	0
abnormal	0
cardiomyocytes	0
.	0

This	0
protective	0
effect	0
did	0
not	0
depend	0
on	0
the	0
time	0
interval	0
between	0
monoHER	1
and	0
D0X	1
administration	0
(	0
P	0
=	0
0	0
.	0
345	0
)	0
.	0

C0NCLUSI0N	0
:	0
The	0
results	0
indicate	0
that	0
in	0
an	0
outpatient	0
clinical	0
setting	0
monoHER	1
may	0
be	0
administered	0
shortly	0
before	0
D0X	1
.	0

Clinical	0
evaluation	0
of	0
adverse	0
effects	0
during	0
bepridil	1
administration	0
for	0
atrial	3
fibrillation	4
and	4
flutter	4
.	0

BACKGR0UND	0
:	0
Bepridil	1
hydrochloride	2
(	0
Bpd	1
)	0
has	0
attracted	0
attention	0
as	0
an	0
effective	0
drug	0
for	0
atrial	3
fibrillation	4
(	0
AF	3
)	0
and	0
atrial	3
flutter	4
(	0
AFL	3
)	0
.	0

However	0
,	0
serious	0
adverse	0
effects	0
,	0
including	0
torsade	3
de	4
pointes	4
(	0
Tdp	3
)	0
,	0
have	0
been	0
reported	0
.	0

METH0DS	0
AND	0
RESULTS	0
:	0
Adverse	0
effects	0
of	0
Bpd	1
requiring	0
discontinuation	0
of	0
treatment	0
were	0
evaluated	0
.	0

Bpd	1
was	0
administered	0
to	0
459	0
patients	0
(	0
361	0
males	0
,	0
63	0
+	0
/	0
-	0
12	0
years	0
old	0
)	0
comprising	0
378	0
AF	3
and	0
81	0
AFL	3
cases	0
.	0

Mean	0
left	0
ventricular	0
ejection	0
fraction	0
and	0
atrial	0
dimension	0
(	0
LAD	0
)	0
were	0
66	0
+	0
/	0
-	0
11	0
%	0
and	0
40	0
+	0
/	0
-	0
6	0
mm	0
,	0
respectively	0
.	0

Adverse	0
effects	0
were	0
observed	0
in	0
19	0
patients	0
(	0
4	0
%	0
)	0
during	0
an	0
average	0
follow	0
-	0
up	0
of	0
20	0
months	0
.	0

There	0
was	0
marked	0
QT	3
prolongation	4
greater	0
than	0
0	0
.	0
55	0
s	0
in	0
13	0
patients	0
,	0
bradycardia	3
less	0
than	0
40	0
beats	0
/	0
min	0
in	0
6	0
patients	0
,	0
dizziness	3
and	0
general	0
fatigue	3
in	0
1	0
patient	0
each	0
.	0

In	0
4	0
of	0
13	0
patients	0
with	0
QT	3
prolongation	4
,	0
Tdp	3
occurred	0
.	0

The	0
major	0
triggering	0
factors	0
of	0
Tdp	3
were	0
hypokalemia	3
and	0
sudden	0
decrease	0
in	0
heart	0
rate	0
.	0

There	0
were	0
no	0
differences	0
in	0
the	0
clinical	0
backgrounds	0
of	0
the	0
patients	0
with	0
and	0
without	0
Tdp	3
other	0
than	0
LAD	0
and	0
age	0
,	0
which	0
were	0
larger	0
and	0
older	0
in	0
the	0
patients	0
with	0
Tdp	3
.	0

C0NCLUSI0N	0
:	0
Careful	0
observation	0
of	0
serum	0
potassium	1
concentration	0
and	0
the	0
ECG	0
should	0
always	0
be	0
done	0
during	0
Bpd	1
administration	0
,	0
particularly	0
in	0
elderly	0
patients	0
.	0

Enhanced	0
isoproterenol	1
-	0
induced	0
cardiac	3
hypertrophy	4
in	0
transgenic	0
rats	0
with	0
low	0
brain	0
angiotensinogen	0
.	0

We	0
have	0
previously	0
shown	0
that	0
a	0
permanent	0
deficiency	0
in	0
the	0
brain	0
renin	0
-	0
angiotensin	1
system	0
(	0
RAS	0
)	0
may	0
increase	0
the	0
sensitivity	0
of	0
the	0
baroreflex	0
control	0
of	0
heart	0
rate	0
.	0

In	0
this	0
study	0
we	0
aimed	0
at	0
studying	0
the	0
involvement	0
of	0
the	0
brain	0
RAS	0
in	0
the	0
cardiac	0
reactivity	0
to	0
the	0
beta	0
-	0
adrenoceptor	0
(	0
beta	0
-	0
AR	0
)	0
agonist	0
isoproterenol	1
(	0
Iso	1
)	0
.	0

Transgenic	0
rats	0
with	0
low	0
brain	0
angiotensinogen	0
(	0
TGR	0
)	0
were	0
used	0
.	0

In	0
isolated	0
hearts	0
,	0
Iso	1
induced	0
a	0
significantly	0
greater	0
increase	0
in	0
left	0
ventricular	0
(	0
LV	0
)	0
pressure	0
and	0
maximal	0
contraction	0
(	0
+	0
dP	0
/	0
dt	0
(	0
max	0
)	0
)	0
in	0
the	0
TGR	0
than	0
in	0
the	0
Sprague	0
-	0
Dawley	0
(	0
SD	0
)	0
rats	0
.	0

LV	3
hypertrophy	4
induced	0
by	0
Iso	1
treatment	0
was	0
significantly	0
higher	0
in	0
TGR	0
than	0
in	0
SD	0
rats	0
(	0
in	0
g	0
LV	0
wt	0
/	0
100	0
g	0
body	0
wt	0
,	0
0	0
.	0
28	0
+	0
/	0
-	0
0	0
.	0
004	0
vs	0
.	0
0	0
.	0
24	0
+	0
/	0
-	0
0	0
.	0
004	0
,	0
respectively	0
)	0
.	0

The	0
greater	0
LV	3
hypertrophy	4
in	0
TGR	0
rats	0
was	0
associated	0
with	0
more	0
pronounced	0
downregulation	0
of	0
beta	0
-	0
AR	0
and	0
upregulation	0
of	0
LV	0
beta	0
-	0
AR	0
kinase	0
-	0
1	0
mRNA	0
levels	0
compared	0
with	0
those	0
in	0
SD	0
rats	0
.	0

The	0
decrease	0
in	0
the	0
heart	0
rate	0
(	0
HR	0
)	0
induced	0
by	0
the	0
beta	0
-	0
AR	0
antagonist	0
metoprolol	1
in	0
conscious	0
rats	0
was	0
significantly	0
attenuated	0
in	0
TGR	0
compared	0
with	0
SD	0
rats	0
(	0
-	0
9	0
.	0
9	0
+	0
/	0
-	0
1	0
.	0
7	0
%	0
vs	0
.	0
-	0
18	0
.	0
1	0
+	0
/	0
-	0
1	0
.	0
5	0
%	0
)	0
,	0
whereas	0
the	0
effect	0
of	0
parasympathetic	0
blockade	0
by	0
atropine	1
on	0
HR	0
was	0
similar	0
in	0
both	0
strains	0
.	0

These	0
results	0
indicate	0
that	0
TGR	0
are	0
more	0
sensitive	0
to	0
beta	0
-	0
AR	0
agonist	0
-	0
induced	0
cardiac	3
inotropic	4
response	0
and	0
hypertrophy	3
,	0
possibly	0
due	0
to	0
chronically	0
low	0
sympathetic	0
outflow	0
directed	0
to	0
the	0
heart	0
.	0

Drug	0
-	0
induced	0
long	3
QT	4
syndrome	4
in	0
injection	0
drug	0
users	0
receiving	0
methadone	1
:	0
high	0
frequency	0
in	0
hospitalized	0
patients	0
and	0
risk	0
factors	0
.	0

BACKGR0UND	0
:	0
Drug	0
-	0
induced	0
long	3
QT	4
syndrome	4
is	0
a	0
serious	0
adverse	0
drug	0
reaction	0
.	0

Methadone	1
prolongs	0
the	0
QT	0
interval	0
in	0
vitro	0
in	0
a	0
dose	0
-	0
dependent	0
manner	0
.	0

In	0
the	0
inpatient	0
setting	0
,	0
the	0
frequency	0
of	0
QT	3
interval	4
prolongation	4
with	0
methadone	1
treatment	0
,	0
its	0
dose	0
dependence	0
,	0
and	0
the	0
importance	0
of	0
cofactors	0
such	0
as	0
drug	0
-	0
drug	0
interactions	0
remain	0
unknown	0
.	0

METH0DS	0
:	0
We	0
performed	0
a	0
systematic	0
,	0
retrospective	0
study	0
comparing	0
active	0
or	0
former	0
intravenous	0
drug	0
users	0
receiving	0
methadone	1
and	0
those	0
not	0
receiving	0
methadone	1
among	0
all	0
patients	0
hospitalized	0
over	0
a	0
5	0
-	0
year	0
period	0
in	0
a	0
tertiary	0
care	0
hospital	0
.	0

A	0
total	0
of	0
167	0
patients	0
receiving	0
methadone	1
fulfilled	0
the	0
inclusion	0
criteria	0
and	0
were	0
compared	0
with	0
a	0
control	0
group	0
of	0
80	0
injection	0
drug	0
users	0
not	0
receiving	0
methadone	1
.	0

In	0
addition	0
to	0
methadone	1
dose	0
,	0
15	0
demographic	0
,	0
biological	0
,	0
and	0
pharmacological	0
variables	0
were	0
considered	0
as	0
potential	0
risk	0
factors	0
for	0
QT	3
prolongation	4
.	0

RESULTS	0
:	0
Among	0
167	0
methadone	1
maintenance	0
patients	0
,	0
the	0
prevalence	0
of	0
QTc	0
prolongation	0
to	0
0	0
.	0
50	0
second	0
(	0
(	0
1	0
/	0
2	0
)	0
)	0
or	0
longer	0
was	0
16	0
.	0
2	0
%	0
compared	0
with	0
0	0
%	0
in	0
80	0
control	0
subjects	0
.	0

Six	0
patients	0
(	0
3	0
.	0
6	0
%	0
)	0
in	0
the	0
methadone	1
group	0
presented	0
torsades	3
de	4
pointes	4
.	0

QTc	0
length	0
was	0
weakly	0
but	0
significantly	0
associated	0
with	0
methadone	1
daily	0
dose	0
(	0
Spearman	0
rank	0
correlation	0
coefficient	0
,	0
0	0
.	0
20	0
;	0
P	0
<	0
.	0
01	0
)	0
.	0

Multivariate	0
regression	0
analysis	0
allowed	0
attribution	0
of	0
31	0
.	0
8	0
%	0
of	0
QTc	0
variability	0
to	0
methadone	1
dose	0
,	0
cytochrome	0
P	0
-	0
450	0
3A4	0
drug	0
-	0
drug	0
interactions	0
,	0
hypokalemia	3
,	0
and	0
altered	0
liver	0
function	0
.	0

C0NCLUSI0NS	0
:	0
QT	3
interval	4
prolongation	4
in	0
methadone	1
maintenance	0
patients	0
hospitalized	0
in	0
a	0
tertiary	0
care	0
center	0
is	0
a	0
frequent	0
finding	0
.	0

Methadone	1
dose	0
,	0
presence	0
of	0
cytochrome	0
P	0
-	0
450	0
3A4	0
inhibitors	0
,	0
potassium	1
level	0
,	0
and	0
liver	0
function	0
contribute	0
to	0
QT	3
prolongation	4
.	0

Long	3
QT	4
syndrome	4
can	0
occur	0
with	0
low	0
doses	0
of	0
methadone	1
.	0

Mechanisms	0
of	0
hypertension	3
induced	0
by	0
nitric	1
oxide	2
(	0
N0	1
)	0
deficiency	0
:	0
focus	0
on	0
venous	0
function	0
.	0

Loss	0
of	0
endothelial	0
cell	0
-	0
derived	0
nitric	1
oxide	2
(	0
N0	1
)	0
in	0
hypertension	3
is	0
a	0
hallmark	0
of	0
arterial	3
dysfunction	4
.	0

Experimental	0
hypertension	3
created	0
by	0
the	0
removal	0
of	0
N0	1
,	0
however	0
,	0
involves	0
mechanisms	0
in	0
addition	0
to	0
decreased	0
arterial	0
vasodilator	0
activity	0
.	0

These	0
include	0
augmented	0
endothelin	0
-	0
1	0
(	0
ET	0
-	0
1	0
)	0
release	0
,	0
increased	0
sympathetic	0
nervous	0
system	0
activity	0
,	0
and	0
elevated	0
tissue	0
oxidative	0
stress	0
.	0

We	0
hypothesized	0
that	0
increased	0
venous	0
smooth	0
muscle	0
(	0
venomotor	0
)	0
tone	0
plays	0
a	0
role	0
in	0
Nomega	1
-	2
nitro	2
-	2
L	2
-	2
arginine	2
(	0
LNNA	1
)	0
hypertension	3
through	0
these	0
mechanisms	0
.	0

Rats	0
were	0
treated	0
with	0
the	0
N0	1
synthase	0
inhibitor	0
LNNA	1
(	0
0	0
.	0
5	0
g	0
/	0
L	0
in	0
drinking	0
water	0
)	0
for	0
2	0
weeks	0
.	0

Mean	0
arterial	0
pressure	0
of	0
conscious	0
rats	0
was	0
119	0
+	0
/	0
-	0
2	0
mm	0
Hg	0
in	0
control	0
and	0
194	0
+	0
/	0
-	0
5	0
mm	0
Hg	0
in	0
LNNA	1
rats	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

Carotid	0
arteries	0
and	0
vena	0
cava	0
were	0
removed	0
for	0
measurement	0
of	0
isometric	0
contraction	0
.	0

Maximal	0
contraction	0
to	0
norepinephrine	1
was	0
modestly	0
reduced	0
in	0
arteries	0
from	0
LNNA	1
compared	0
with	0
control	0
rats	0
whereas	0
the	0
maximum	0
contraction	0
to	0
ET	0
-	0
1	0
was	0
significantly	0
reduced	0
(	0
54	0
%	0
control	0
)	0
.	0

Maximum	0
contraction	0
of	0
vena	0
cava	0
to	0
norepinephrine	1
(	0
37	0
%	0
control	0
)	0
also	0
was	0
reduced	0
but	0
no	0
change	0
in	0
response	0
to	0
ET	0
-	0
1	0
was	0
observed	0
.	0

Mean	0
circulatory	0
filling	0
pressure	0
,	0
an	0
in	0
vivo	0
measure	0
of	0
venomotor	0
tone	0
,	0
was	0
not	0
elevated	0
in	0
LNNA	1
hypertension	3
at	0
1	0
or	0
2	0
weeks	0
after	0
LNNA	1
.	0

The	0
superoxide	1
scavenger	0
tempol	1
(	0
30	0
,	0
100	0
,	0
and	0
300	0
micromol	0
kg	0
(	0
-	0
1	0
)	0
,	0
IV	0
)	0
did	0
not	0
change	0
arterial	0
pressure	0
in	0
control	0
rats	0
but	0
caused	0
a	0
dose	0
-	0
dependent	0
decrease	0
in	0
LNNA	1
rats	0
(	0
-	0
18	0
+	0
/	0
-	0
8	0
,	0
-	0
26	0
+	0
/	0
-	0
15	0
,	0
and	0
-	0
54	0
+	0
/	0
-	0
11	0
mm	0
Hg	0
)	0
.	0

Similarly	0
,	0
ganglionic	0
blockade	0
with	0
hexamethonium	1
caused	0
a	0
significantly	0
greater	0
fall	0
in	0
LNNA	1
hypertensive	3
rats	0
(	0
76	0
+	0
/	0
-	0
9	0
mm	0
Hg	0
)	0
compared	0
with	0
control	0
rats	0
(	0
35	0
+	0
/	0
-	0
10	0
mm	0
Hg	0
)	0
.	0

Carotid	0
arteries	0
,	0
vena	0
cava	0
,	0
and	0
sympathetic	0
ganglia	0
from	0
LNNA	1
rats	0
had	0
higher	0
basal	0
levels	0
of	0
superoxide	1
compared	0
with	0
those	0
from	0
control	0
rats	0
.	0

These	0
data	0
suggest	0
that	0
while	0
N0	1
deficiency	0
increases	0
oxidative	0
stress	0
and	0
sympathetic	0
activity	0
in	0
both	0
arterial	0
and	0
venous	0
vessels	0
,	0
the	0
impact	0
on	0
veins	0
does	0
not	0
make	0
a	0
major	0
contribution	0
to	0
this	0
form	0
of	0
hypertension	3
.	0

Association	0
of	0
DRD2	0
polymorphisms	0
and	0
chlorpromazine	1
-	0
induced	0
extrapyramidal	3
syndrome	4
in	0
Chinese	0
schizophrenic	3
patients	0
.	0

AIM	0
:	0
Extrapyramidal	3
syndrome	4
(	0
EPS	3
)	0
is	0
most	0
commonly	0
affected	0
by	0
typical	0
antipsychotic	0
drugs	0
that	0
have	0
a	0
high	0
affinity	0
with	0
the	0
D2	0
receptor	0
.	0

Recently	0
,	0
many	0
research	0
groups	0
have	0
reported	0
on	0
the	0
positive	0
relationship	0
between	0
the	0
genetic	0
variations	0
in	0
the	0
DRD2	0
gene	0
and	0
the	0
therapeutic	0
response	0
in	0
schizophrenia	3
patients	0
as	0
a	0
result	0
of	0
the	0
role	0
of	0
variations	0
in	0
the	0
receptor	0
in	0
modulating	0
receptor	0
expression	0
.	0

In	0
this	0
study	0
,	0
we	0
evaluate	0
the	0
role	0
DRD2	0
plays	0
in	0
chlorpromazine	1
-	0
induced	0
EPS	3
in	0
schizophrenic	3
patients	0
.	0

METH0DS	0
:	0
We	0
identified	0
seven	0
SNP	0
(	0
single	0
nucleotide	0
polymorphism	0
)	0
(	0
-	0
141Cins	0
>	0
del	0
,	0
TaqIB	0
,	0
TaqID	0
,	0
Ser311Cys	0
,	0
rs6275	0
,	0
rs6277	0
and	0
TaqIA	0
)	0
in	0
the	0
DRD2	0
gene	0
in	0
146	0
schizophrenic	3
inpatients	0
(	0
59	0
with	0
EPS	3
and	0
87	0
without	0
EPS	3
according	0
to	0
the	0
Simpson	0
-	0
Angus	0
Scale	0
)	0
treated	0
with	0
chlorpromazine	1
after	0
8	0
weeks	0
.	0

The	0
alleles	0
of	0
all	0
loci	0
were	0
determined	0
by	0
PCR	0
(	0
polymerase	0
chain	0
reaction	0
)	0
.	0

RESULTS	0
:	0
Polymorphisms	0
TaqID	0
,	0
Ser311Cys	0
and	0
rs6277	0
were	0
not	0
polymorphic	0
in	0
the	0
population	0
recruited	0
in	0
the	0
present	0
study	0
.	0

No	0
statistical	0
significance	0
was	0
found	0
in	0
the	0
allele	0
distribution	0
of	0
-	0
141Cins	0
>	0
del	0
,	0
TaqIB	0
,	0
rs6275	0
and	0
TaqIA	0
or	0
in	0
the	0
estimated	0
haplotypes	0
(	0
constituted	0
by	0
TaqIB	0
,	0
rs6275	0
and	0
TaqIA	0
)	0
in	0
linkage	0
disequilibrium	0
between	0
the	0
two	0
groups	0
.	0

C0NCLUSI0N	0
:	0
0ur	0
results	0
did	0
not	0
lend	0
strong	0
support	0
to	0
the	0
view	0
that	0
the	0
genetic	0
variation	0
of	0
the	0
DRD2	0
gene	0
plays	0
a	0
major	0
role	0
in	0
the	0
individually	0
variable	0
adverse	0
effect	0
induced	0
by	0
chlorpromazine	1
,	0
at	0
least	0
in	0
Chinese	0
patients	0
with	0
schizophrenia	3
.	0

0ur	0
results	0
confirmed	0
a	0
previous	0
study	0
on	0
the	0
relationship	0
between	0
DRD2	0
and	0
EPS	3
in	0
Caucasians	0
.	0

Physical	0
training	0
decreases	0
susceptibility	0
to	0
subsequent	0
pilocarpine	1
-	0
induced	0
seizures	3
in	0
the	0
rat	0
.	0

Regular	0
motor	0
activity	0
has	0
many	0
benefits	0
for	0
mental	0
and	0
physical	0
condition	0
but	0
its	0
implications	0
for	0
epilepsy	3
are	0
still	0
controversial	0
.	0

In	0
order	0
to	0
elucidate	0
this	0
problem	0
,	0
we	0
have	0
studied	0
the	0
effect	0
of	0
long	0
-	0
term	0
physical	0
activity	0
on	0
susceptibility	0
to	0
subsequent	0
seizures	3
.	0

Male	0
Wistar	0
rats	0
were	0
subjected	0
to	0
repeated	0
training	0
sessions	0
in	0
a	0
treadmill	0
and	0
swimming	0
pool	0
.	0

Thereafter	0
,	0
seizures	3
were	0
induced	0
by	0
pilocarpine	1
injections	0
in	0
trained	0
and	0
non	0
-	0
trained	0
control	0
groups	0
.	0

During	0
the	0
acute	0
period	0
of	0
status	3
epilepticus	4
,	0
we	0
measured	0
:	0
(	0
1	0
)	0
the	0
latency	0
of	0
the	0
first	0
motor	0
sign	0
,	0
(	0
2	0
)	0
the	0
intensity	0
of	0
seizures	3
,	0
(	0
3	0
)	0
the	0
time	0
when	0
it	0
occurred	0
within	0
the	0
6	0
-	0
h	0
observation	0
period	0
,	0
and	0
(	0
4	0
)	0
the	0
time	0
when	0
the	0
acute	0
period	0
ended	0
.	0

All	0
these	0
behavioral	0
parameters	0
showed	0
statistically	0
significant	0
changes	0
suggesting	0
that	0
regular	0
physical	0
exercises	0
decrease	0
susceptibility	0
to	0
subsequently	0
induced	0
seizures	3
and	0
ameliorate	0
the	0
course	0
of	0
experimentally	0
induced	0
status	3
epilepticus	4
.	0

Tonic	0
dopaminergic	0
stimulation	0
impairs	3
associative	4
learning	4
in	0
healthy	0
subjects	0
.	0

Endogenous	0
dopamine	1
plays	0
a	0
central	0
role	0
in	0
salience	0
coding	0
during	0
associative	0
learning	0
.	0

Administration	0
of	0
the	0
dopamine	1
precursor	0
levodopa	1
enhances	0
learning	0
in	0
healthy	0
subjects	0
and	0
stroke	3
patients	0
.	0

Because	0
levodopa	1
increases	0
both	0
phasic	0
and	0
tonic	0
dopaminergic	0
neurotransmission	0
,	0
the	0
critical	0
mechanism	0
mediating	0
the	0
enhancement	0
of	0
learning	0
is	0
unresolved	0
.	0

We	0
here	0
probed	0
how	0
selective	0
tonic	0
dopaminergic	0
stimulation	0
affects	0
associative	0
learning	0
.	0

Forty	0
healthy	0
subjects	0
were	0
trained	0
in	0
a	0
novel	0
vocabulary	0
of	0
45	0
concrete	0
nouns	0
over	0
the	0
course	0
of	0
5	0
consecutive	0
training	0
days	0
in	0
a	0
prospective	0
,	0
randomized	0
,	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
design	0
.	0

Subjects	0
received	0
the	0
tonically	0
stimulating	0
dopamine	1
-	0
receptor	0
agonist	0
pergolide	1
(	0
0	0
.	0
1	0
mg	0
)	0
vs	0
placebo	0
120	0
min	0
before	0
training	0
on	0
each	0
training	0
day	0
.	0

The	0
dopamine	1
agonist	0
significantly	0
impaired	3
novel	4
word	4
learning	4
compared	0
to	0
placebo	0
.	0

This	0
learning	0
decrement	0
persisted	0
up	0
to	0
the	0
last	0
follow	0
-	0
up	0
4	0
weeks	0
post	0
-	0
training	0
.	0

Subjects	0
treated	0
with	0
pergolide	1
also	0
showed	0
restricted	0
emotional	0
responses	0
compared	0
to	0
the	0
PLACEB0	0
group	0
.	0

The	0
extent	0
of	0
'	0
flattened	0
'	0
affect	0
with	0
pergolide	1
was	0
related	0
to	0
the	0
degree	0
of	0
learning	0
inhibition	0
.	0

These	0
findings	0
suggest	0
that	0
tonic	0
occupation	0
of	0
dopamine	1
receptors	0
impairs	0
learning	0
by	0
competition	0
with	0
phasic	0
dopamine	1
signals	0
.	0

Thus	0
,	0
phasic	0
signaling	0
seems	0
to	0
be	0
the	0
critical	0
mechanism	0
by	0
which	0
dopamine	1
enhances	0
associative	0
learning	0
in	0
healthy	0
subjects	0
and	0
stroke	3
patients	0
.	0

Minocycline	1
-	0
induced	0
vasculitis	3
fulfilling	0
the	0
criteria	0
of	0
polyarteritis	3
nodosa	4
.	0

A	0
47	0
-	0
year	0
-	0
old	0
man	0
who	0
had	0
been	0
taking	0
minocycline	1
for	0
palmoplantar	3
pustulosis	4
developed	0
fever	3
,	0
myalgias	3
,	0
polyneuropathy	3
,	0
and	0
testicular	3
pain	4
,	0
with	0
elevated	0
C	0
-	0
reactive	0
protein	0
(	0
CRP	0
)	0
.	0

Neither	0
myeloperoxidase	0
-	0
nor	0
proteinase	0
-	0
3	0
-	0
antineutrophil	0
cytoplasmic	0
antibody	0
was	0
positive	0
.	0

These	0
manifestations	0
met	0
the	0
American	0
College	0
of	0
Rheumatology	0
1990	0
criteria	0
for	0
the	0
classification	0
of	0
polyarteritis	3
nodosa	4
.	0

Stopping	0
minocycline	1
led	0
to	0
amelioration	0
of	0
symptoms	0
and	0
normalization	0
of	0
CRP	0
level	0
.	0

To	0
our	0
knowledge	0
,	0
this	0
is	0
the	0
second	0
case	0
of	0
minocycline	1
-	0
induced	0
vasculitis	3
satisfying	0
the	0
criteria	0
.	0

Differential	0
diagnosis	0
for	0
drug	0
-	0
induced	0
disease	0
is	0
invaluable	0
even	0
for	0
patients	0
with	0
classical	0
polyarteritis	3
nodosa	4
.	0

Intramuscular	0
hepatitis	3
B	4
immune	0
globulin	0
combined	0
with	0
lamivudine	1
in	0
prevention	0
of	0
hepatitis	3
B	4
recurrence	0
after	0
liver	0
transplantation	0
.	0

BACKGR0UND	0
:	0
Combined	0
hepatitis	3
B	4
immune	0
globulin	0
(	0
HBIg	0
)	0
and	0
lamivudine	1
in	0
prophylaxis	0
of	0
the	0
recurrence	0
of	0
hepatitis	3
B	4
after	0
liver	0
transplantation	0
has	0
significantly	0
improved	0
the	0
survival	0
of	0
HBsAg	1
positive	0
patients	0
.	0

This	0
study	0
was	0
undertaken	0
to	0
evaluate	0
the	0
outcomes	0
of	0
liver	0
transplantation	0
for	0
patients	0
with	0
hepatitis	3
B	4
virus	0
(	0
HBV	0
)	0
.	0

METH0DS	0
:	0
A	0
retrospective	0
chart	0
analysis	0
and	0
a	0
review	0
of	0
the	0
organ	0
transplant	0
database	0
identified	0
51	0
patients	0
(	0
43	0
men	0
and	0
8	0
women	0
)	0
transplanted	0
for	0
benign	0
HBV	0
-	0
related	0
cirrhotic	3
diseases	4
between	0
June	0
2002	0
and	0
December	0
2004	0
who	0
had	0
survived	0
more	0
than	0
3	0
months	0
.	0

HBIg	0
was	0
administered	0
intravenously	0
during	0
the	0
first	0
week	0
and	0
intramuscularly	0
thereafter	0
.	0

RESULTS	0
:	0
At	0
a	0
median	0
follow	0
-	0
up	0
of	0
14	0
.	0
1	0
months	0
,	0
the	0
overall	0
recurrence	0
rate	0
in	0
the	0
51	0
patients	0
was	0
3	0
.	0
9	0
%	0
(	0
2	0
/	0
51	0
)	0
.	0

The	0
overall	0
patient	0
survival	0
was	0
88	0
.	0
3	0
%	0
,	0
and	0
82	0
.	0
4	0
%	0
after	0
1	0
and	0
2	0
years	0
,	0
respectively	0
.	0

A	0
daily	0
oral	0
dose	0
of	0
100	0
mg	0
lamivudine	1
for	0
2	0
weeks	0
before	0
transplantation	0
for	0
10	0
patients	0
enabled	0
57	0
.	0
1	0
%	0
(	0
4	0
/	0
7	0
)	0
and	0
62	0
.	0
5	0
%	0
(	0
5	0
/	0
8	0
)	0
of	0
HBV	0
-	0
DNA	0
and	0
HBeAg	1
positive	0
patients	0
respectively	0
to	0
convert	0
to	0
be	0
negative	0
.	0

Intramuscular	0
HBIg	0
was	0
well	0
tolerated	0
in	0
all	0
patients	0
.	0

C0NCLUSI0N	0
:	0
Lamivudine	1
combined	0
with	0
intramuscular	0
HBIg	0
can	0
effectively	0
prevent	0
allograft	0
from	0
the	0
recurrence	0
of	0
HBV	0
after	0
liver	0
transplantation	0
.	0

Anticonvulsant	0
effect	0
of	0
eslicarbazepine	1
acetate	2
(	0
BIA	1
2	2
-	2
093	2
)	0
on	0
seizures	3
induced	0
by	0
microperfusion	0
of	0
picrotoxin	1
in	0
the	0
hippocampus	0
of	0
freely	0
moving	0
rats	0
.	0

Eslicarbazepine	1
acetate	2
(	0
BIA	1
2	2
-	2
093	2
,	0
S	1
-	2
(	2
-	2
)	2
-	2
10	2
-	2
acetoxy	2
-	2
10	2
,	2
11	2
-	2
dihydro	2
-	2
5H	2
-	2
dibenzo	2
/	2
b	2
,	2
f	2
/	2
azepine	2
-	2
5	2
-	2
carboxamide	2
)	0
is	0
a	0
novel	0
antiepileptic	0
drug	0
,	0
now	0
in	0
Phase	0
III	0
clinical	0
trials	0
,	0
designed	0
with	0
the	0
aim	0
of	0
improving	0
efficacy	0
and	0
safety	0
in	0
comparison	0
with	0
the	0
structurally	0
related	0
drugs	0
carbamazepine	1
(	0
CBZ	1
)	0
and	0
oxcarbazepine	1
(	0
0XC	1
)	0
.	0

We	0
have	0
studied	0
the	0
effects	0
of	0
oral	0
treatment	0
with	0
eslicarbazepine	1
acetate	2
on	0
a	0
whole	0
-	0
animal	0
model	0
in	0
which	0
partial	0
seizures	3
can	0
be	0
elicited	0
repeatedly	0
on	0
different	0
days	0
without	0
changes	0
in	0
threshold	0
or	0
seizure	3
patterns	0
.	0

In	0
the	0
animals	0
treated	0
with	0
threshold	0
doses	0
of	0
picrotoxin	1
,	0
the	0
average	0
number	0
of	0
seizures	3
was	0
2	0
.	0
3	0
+	0
/	0
-	0
1	0
.	0
2	0
,	0
and	0
average	0
seizure	3
duration	0
was	0
39	0
.	0
5	0
+	0
/	0
-	0
8	0
.	0
4s	0
.	0

Pre	0
-	0
treatment	0
with	0
a	0
dose	0
of	0
30	0
mg	0
/	0
kg	0
2h	0
before	0
picrotoxin	1
microperfusion	0
prevented	0
seizures	3
in	0
the	0
75	0
%	0
of	0
the	0
rats	0
.	0

Lower	0
doses	0
(	0
3	0
and	0
10mg	0
/	0
kg	0
)	0
did	0
not	0
suppress	0
seizures	3
,	0
however	0
,	0
after	0
administration	0
of	0
10mg	0
/	0
kg	0
,	0
significant	0
reductions	0
in	0
seizures	3
duration	0
(	0
24	0
.	0
3	0
+	0
/	0
-	0
6	0
.	0
8s	0
)	0
and	0
seizure	3
number	0
(	0
1	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
34	0
)	0
were	0
found	0
.	0

No	0
adverse	0
effects	0
of	0
eslicarbazepine	1
acetate	2
were	0
observed	0
in	0
the	0
behavioral	0
/	0
EEG	0
patterns	0
studied	0
,	0
including	0
sleep	0
/	0
wakefulness	0
cycle	0
,	0
at	0
the	0
doses	0
studied	0
.	0

Acute	3
renal	4
failure	4
associated	0
with	0
prolonged	0
intake	0
of	0
slimming	0
pills	0
containing	0
anthraquinones	1
.	0

Chinese	1
herbal	2
medicine	0
preparations	0
are	0
widely	0
available	0
and	0
often	0
regarded	0
by	0
the	0
public	0
as	0
natural	0
and	0
safe	0
remedies	0
for	0
a	0
variety	0
of	0
medical	0
conditions	0
.	0

Nephropathy	3
caused	0
by	0
Chinese	1
herbs	2
has	0
previously	0
been	0
reported	0
,	0
usually	0
involving	0
the	0
use	0
of	0
aristolochic	1
acids	2
.	0

We	0
report	0
a	0
23	0
-	0
year	0
-	0
old	0
woman	0
who	0
developed	0
acute	3
renal	4
failure	4
following	0
prolonged	0
use	0
of	0
a	0
proprietary	0
Chinese	1
herbal	2
slimming	0
pill	0
that	0
contained	0
anthraquinone	1
derivatives	0
,	0
extracted	0
from	0
Rhizoma	0
Rhei	0
(	0
rhubarb	0
)	0
.	0

The	0
renal	3
injury	4
was	0
probably	0
aggravated	0
by	0
the	0
concomitant	0
intake	0
of	0
a	0
non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
drug	0
,	0
diclofenac	1
.	0

Renal	0
pathology	0
was	0
that	0
of	0
hypocellular	0
interstitial	0
fibrosis	3
.	0

Spontaneous	0
renal	0
recovery	0
occurred	0
upon	0
cessation	0
of	0
the	0
slimming	0
pills	0
,	0
but	0
mild	0
interstitial	0
fibrosis	3
and	0
tubular	0
atrophy	3
was	0
still	0
evident	0
histologically	0
4	0
months	0
later	0
.	0

Although	0
a	0
causal	0
relationship	0
between	0
the	0
use	0
of	0
an	0
anthraquinone	1
-	0
containing	0
herbal	0
agent	0
and	0
renal	3
injury	4
remains	0
to	0
be	0
proven	0
,	0
phytotherapy	0
-	0
associated	0
interstitial	0
nephropathy	3
should	0
be	0
considered	0
in	0
patients	0
who	0
present	0
with	0
unexplained	0
renal	3
failure	4
.	0

Chloroacetaldehyde	1
as	0
a	0
sulfhydryl	1
reagent	0
:	0
the	0
role	0
of	0
critical	0
thiol	1
groups	0
in	0
ifosfamide	1
nephropathy	3
.	0

Chloroacetaldehyde	1
(	0
CAA	1
)	0
is	0
a	0
metabolite	0
of	0
the	0
alkylating	0
agent	0
ifosfamide	1
(	0
IF0	1
)	0
and	0
putatively	0
responsible	0
for	0
renal	3
damage	4
following	0
anti	0
-	0
tumor	3
therapy	0
with	0
IF0	1
.	0

Depletion	0
of	0
sulfhydryl	1
(	0
SH	1
)	0
groups	0
has	0
been	0
reported	0
from	0
cell	0
culture	0
,	0
animal	0
and	0
clinical	0
studies	0
.	0

In	0
this	0
work	0
the	0
effect	0
of	0
CAA	1
on	0
human	0
proximal	0
tubule	0
cells	0
in	0
primary	0
culture	0
(	0
hRPTEC	0
)	0
was	0
investigated	0
.	0

Toxicity	3
of	0
CAA	1
was	0
determined	0
by	0
protein	0
content	0
,	0
cell	0
number	0
,	0
LDH	0
release	0
,	0
trypan	1
blue	2
exclusion	0
assay	0
and	0
caspase	0
-	0
3	0
activity	0
.	0

Free	0
thiols	1
were	0
measured	0
by	0
the	0
method	0
of	0
Ellman	0
.	0

CAA	1
reduced	0
hRPTEC	0
cell	0
number	0
and	0
protein	0
,	0
induced	0
a	0
loss	0
in	0
free	0
intracellular	0
thiols	1
and	0
an	0
increase	0
in	0
necrosis	3
markers	0
.	0

CAA	1
but	0
not	0
acrolein	1
inhibited	0
the	0
cysteine	1
proteases	0
caspase	0
-	0
3	0
,	0
caspase	0
-	0
8	0
and	0
cathepsin	0
B	0
.	0

Caspase	0
activation	0
by	0
cisplatin	1
was	0
inhibited	0
by	0
CAA	1
.	0

In	0
cells	0
stained	0
with	0
fluorescent	0
dyes	0
targeting	0
lysosomes	0
,	0
CAA	1
induced	0
an	0
increase	0
in	0
lysosomal	0
size	0
and	0
lysosomal	0
leakage	0
.	0

The	0
effects	0
of	0
CAA	1
on	0
cysteine	1
protease	0
activities	0
and	0
thiols	1
could	0
be	0
reproduced	0
in	0
cell	0
lysate	0
.	0

Acidification	0
,	0
which	0
slowed	0
the	0
reaction	0
of	0
CAA	1
with	0
thiol	1
donors	0
,	0
could	0
also	0
attenuate	0
effects	0
of	0
CAA	1
on	0
necrosis	3
markers	0
,	0
thiol	1
depletion	0
and	0
cysteine	1
protease	0
inhibition	0
in	0
living	0
cells	0
.	0

Thus	0
,	0
CAA	1
directly	0
reacts	0
with	0
cellular	0
protein	0
and	0
non	0
-	0
protein	0
thiols	1
,	0
mediating	0
its	0
toxicity	3
on	0
hRPTEC	0
.	0

This	0
effect	0
can	0
be	0
reduced	0
by	0
acidification	0
.	0

Therefore	0
,	0
urinary	0
acidification	0
could	0
be	0
an	0
option	0
to	0
prevent	0
IF0	1
nephropathy	3
in	0
patients	0
.	0

Stereological	0
methods	0
reveal	0
the	0
robust	0
size	0
and	0
stability	0
of	0
ectopic	0
hilar	0
granule	0
cells	0
after	0
pilocarpine	1
-	0
induced	0
status	3
epilepticus	4
in	0
the	0
adult	0
rat	0
.	0

Following	0
status	3
epilepticus	4
in	0
the	0
rat	0
,	0
dentate	0
granule	0
cell	0
neurogenesis	0
increases	0
greatly	0
,	0
and	0
many	0
of	0
the	0
new	0
neurons	0
appear	0
to	0
develop	0
ectopically	0
,	0
in	0
the	0
hilar	0
region	0
of	0
the	0
hippocampal	0
formation	0
.	0

It	0
has	0
been	0
suggested	0
that	0
the	0
ectopic	0
hilar	0
granule	0
cells	0
could	0
contribute	0
to	0
the	0
spontaneous	0
seizures	3
that	0
ultimately	0
develop	0
after	0
status	3
epilepticus	4
.	0

However	0
,	0
the	0
population	0
has	0
never	0
been	0
quantified	0
,	0
so	0
it	0
is	0
unclear	0
whether	0
it	0
is	0
substantial	0
enough	0
to	0
have	0
a	0
strong	0
influence	0
on	0
epileptogenesis	0
.	0

To	0
quantify	0
this	0
population	0
,	0
the	0
total	0
number	0
of	0
ectopic	0
hilar	0
granule	0
cells	0
was	0
estimated	0
using	0
unbiased	0
stereology	0
at	0
different	0
times	0
after	0
pilocarpine	1
-	0
induced	0
status	3
epilepticus	4
.	0

The	0
number	0
of	0
hilar	0
neurons	0
immunoreactive	0
for	0
Prox	0
-	0
1	0
,	0
a	0
granule	0
-	0
cell	0
-	0
specific	0
marker	0
,	0
was	0
estimated	0
using	0
the	0
optical	0
fractionator	0
method	0
.	0

The	0
results	0
indicate	0
that	0
the	0
size	0
of	0
the	0
hilar	0
ectopic	0
granule	0
cell	0
population	0
after	0
status	3
epilepticus	4
is	0
substantial	0
,	0
and	0
stable	0
over	0
time	0
.	0

Interestingly	0
,	0
the	0
size	0
of	0
the	0
population	0
appears	0
to	0
be	0
correlated	0
with	0
the	0
frequency	0
of	0
behavioral	0
seizures	3
,	0
because	0
animals	0
with	0
more	0
ectopic	0
granule	0
cells	0
in	0
the	0
hilus	0
have	0
more	0
frequent	0
behavioral	0
seizures	3
.	0

The	0
hilar	0
ectopic	0
granule	0
cell	0
population	0
does	0
not	0
appear	0
to	0
vary	0
systematically	0
across	0
the	0
septotemporal	0
axis	0
,	0
although	0
it	0
is	0
associated	0
with	0
an	0
increase	0
in	0
volume	0
of	0
the	0
hilus	0
.	0

The	0
results	0
provide	0
new	0
insight	0
into	0
the	0
potential	0
role	0
of	0
ectopic	0
hilar	0
granule	0
cells	0
in	0
the	0
pilocarpine	1
model	0
of	0
temporal	3
lobe	4
epilepsy	4
.	0

A	0
prospective	0
,	0
open	0
-	0
label	0
trial	0
of	0
galantamine	1
in	0
autistic	3
disorder	4
.	0

0BJECTIVE	0
:	0
Post	0
-	0
mortem	0
studies	0
have	0
reported	0
abnormalities	0
of	0
the	0
cholinergic	0
system	0
in	0
autism	3
.	0

The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
assess	0
the	0
use	0
of	0
galantamine	1
,	0
an	0
acetylcholinesterase	0
inhibitor	0
and	0
nicotinic	0
receptor	0
modulator	0
,	0
in	0
the	0
treatment	0
of	0
interfering	0
behaviors	0
in	0
children	0
with	0
autism	3
.	0

METH0DS	0
:	0
Thirteen	0
medication	0
-	0
free	0
children	0
with	0
autism	3
(	0
mean	0
age	0
,	0
8	0
.	0
8	0
+	0
/	0
-	0
3	0
.	0
5	0
years	0
)	0
participated	0
in	0
a	0
12	0
-	0
week	0
,	0
open	0
-	0
label	0
trial	0
of	0
galantamine	1
.	0

Patients	0
were	0
rated	0
monthly	0
by	0
parents	0
on	0
the	0
Aberrant	0
Behavior	0
Checklist	0
(	0
ABC	0
)	0
and	0
the	0
Conners	0
'	0
Parent	0
Rating	0
Scale	0
-	0
Revised	0
,	0
and	0
by	0
a	0
physician	0
using	0
the	0
Children	0
'	0
s	0
Psychiatric	0
Rating	0
Scale	0
and	0
the	0
Clinical	0
Global	0
Impressions	0
scale	0
.	0

RESULTS	0
:	0
Patients	0
showed	0
a	0
significant	0
reduction	0
in	0
parent	0
-	0
rated	0
irritability	3
and	0
social	0
withdrawal	0
on	0
the	0
ABC	0
as	0
well	0
as	0
significant	0
improvements	0
in	0
emotional	0
lability	0
and	0
inattention	0
on	0
the	0
Conners	0
'	0
Parent	0
Rating	0
Scale	0
-	0
-	0
Revised	0
.	0

Similarly	0
,	0
clinician	0
ratings	0
showed	0
reductions	0
in	0
the	0
anger	0
subscale	0
of	0
the	0
Children	0
'	0
s	0
Psychiatric	0
Rating	0
Scale	0
.	0

Eight	0
of	0
13	0
participants	0
were	0
rated	0
as	0
responders	0
on	0
the	0
basis	0
of	0
their	0
improvement	0
scores	0
on	0
the	0
Clinical	0
Global	0
Impressions	0
scale	0
.	0

0verall	0
,	0
galantamine	1
was	0
well	0
-	0
tolerated	0
,	0
with	0
no	0
significant	0
adverse	0
effects	0
apart	0
from	0
headaches	3
in	0
one	0
patient	0
.	0

C0NCLUSI0N	0
:	0
In	0
this	0
open	0
trial	0
,	0
galantamine	1
was	0
well	0
-	0
tolerated	0
and	0
appeared	0
to	0
be	0
beneficial	0
for	0
the	0
treatment	0
of	0
interfering	0
behaviors	0
in	0
children	0
with	0
autism	3
,	0
particularly	0
aggression	3
,	0
behavioral	3
dyscontrol	4
,	0
and	0
inattention	3
.	0

Further	0
controlled	0
trials	0
are	0
warranted	0
.	0

Randomized	0
comparison	0
of	0
olanzapine	1
versus	0
risperidone	1
for	0
the	0
treatment	0
of	0
first	0
-	0
episode	0
schizophrenia	3
:	0
4	0
-	0
month	0
outcomes	0
.	0

0BJECTIVE	0
:	0
The	0
authors	0
compared	0
4	0
-	0
month	0
treatment	0
outcomes	0
for	0
olanzapine	1
versus	0
risperidone	1
in	0
patients	0
with	0
first	0
-	0
episode	0
schizophrenia	3
spectrum	0
disorders	0
.	0

METH0D	0
:	0
0ne	0
hundred	0
twelve	0
subjects	0
(	0
70	0
%	0
male	0
;	0
mean	0
age	0
=	0
23	0
.	0
3	0
years	0
[	0
SD	0
=	0
5	0
.	0
1	0
]	0
)	0
with	0
first	0
-	0
episode	0
schizophrenia	3
(	0
75	0
%	0
)	0
,	0
schizophreniform	3
disorder	4
(	0
17	0
%	0
)	0
,	0
or	0
schizoaffective	3
disorder	4
(	0
8	0
%	0
)	0
were	0
randomly	0
assigned	0
to	0
treatment	0
with	0
olanzapine	1
(	0
2	0
.	0
5	0
-	0
20	0
mg	0
/	0
day	0
)	0
or	0
risperidone	1
(	0
1	0
-	0
6	0
mg	0
/	0
day	0
)	0
.	0

RESULTS	0
:	0
Response	0
rates	0
did	0
not	0
significantly	0
differ	0
between	0
olanzapine	1
(	0
43	0
.	0
7	0
%	0
,	0
95	0
%	0
CI	0
=	0
28	0
.	0
8	0
%	0
-	0
58	0
.	0
6	0
%	0
)	0
and	0
risperidone	1
(	0
54	0
.	0
3	0
%	0
,	0
95	0
%	0
CI	0
=	0
39	0
.	0
9	0
%	0
-	0
68	0
.	0
7	0
%	0
)	0
.	0

Among	0
those	0
responding	0
to	0
treatment	0
,	0
more	0
subjects	0
in	0
the	0
olanzapine	1
group	0
(	0
40	0
.	0
9	0
%	0
,	0
95	0
%	0
CI	0
=	0
16	0
.	0
8	0
%	0
-	0
65	0
.	0
0	0
%	0
)	0
than	0
in	0
the	0
risperidone	1
group	0
(	0
18	0
.	0
9	0
%	0
,	0
95	0
%	0
CI	0
=	0
0	0
%	0
-	0
39	0
.	0
2	0
%	0
)	0
had	0
subsequent	0
ratings	0
not	0
meeting	0
response	0
criteria	0
.	0

Negative	0
symptom	0
outcomes	0
and	0
measures	0
of	0
parkinsonism	3
and	0
akathisia	3
did	0
not	0
differ	0
between	0
medications	0
.	0

Extrapyramidal	3
symptom	4
severity	0
scores	0
were	0
1	0
.	0
4	0
(	0
95	0
%	0
CI	0
=	0
1	0
.	0
2	0
-	0
1	0
.	0
6	0
)	0
with	0
risperidone	1
and	0
1	0
.	0
2	0
(	0
95	0
%	0
CI	0
=	0
1	0
.	0
0	0
-	0
1	0
.	0
4	0
)	0
with	0
olanzapine	1
.	0

Significantly	0
more	0
weight	3
gain	4
occurred	0
with	0
olanzapine	1
than	0
with	0
risperidone	1
:	0
the	0
increase	0
in	0
weight	0
at	0
4	0
months	0
relative	0
to	0
baseline	0
weight	0
was	0
17	0
.	0
3	0
%	0
(	0
95	0
%	0
CI	0
=	0
14	0
.	0
2	0
%	0
-	0
20	0
.	0
5	0
%	0
)	0
with	0
olanzapine	1
and	0
11	0
.	0
3	0
%	0
(	0
95	0
%	0
CI	0
=	0
8	0
.	0
4	0
%	0
-	0
14	0
.	0
3	0
%	0
)	0
with	0
risperidone	1
.	0

Body	0
mass	0
index	0
at	0
baseline	0
and	0
at	0
4	0
months	0
was	0
24	0
.	0
3	0
(	0
95	0
%	0
CI	0
=	0
22	0
.	0
8	0
-	0
25	0
.	0
7	0
)	0
versus	0
28	0
.	0
2	0
(	0
95	0
%	0
CI	0
=	0
26	0
.	0
7	0
-	0
29	0
.	0
7	0
)	0
with	0
olanzapine	1
and	0
23	0
.	0
9	0
(	0
95	0
%	0
CI	0
=	0
22	0
.	0
5	0
-	0
25	0
.	0
3	0
)	0
versus	0
26	0
.	0
7	0
(	0
95	0
%	0
CI	0
=	0
25	0
.	0
2	0
-	0
28	0
.	0
2	0
)	0
with	0
risperidone	1
.	0

C0NCLUSI0NS	0
:	0
Clinical	0
outcomes	0
with	0
risperidone	1
were	0
equal	0
to	0
those	0
with	0
olanzapine	1
,	0
and	0
response	0
may	0
be	0
more	0
stable	0
.	0

0lanzapine	1
may	0
have	0
an	0
advantage	0
for	0
motor	0
side	0
effects	0
.	0

Both	0
medications	0
caused	0
substantial	0
rapid	0
weight	3
gain	4
,	0
but	0
weight	3
gain	4
was	0
greater	0
with	0
olanzapine	1
.	0

Early	0
paracentral	0
visual	3
field	4
loss	4
in	0
patients	0
taking	0
hydroxychloroquine	1
.	0

0BJECTIVE	0
:	0
To	0
review	0
the	0
natural	0
history	0
and	0
ocular	0
and	0
systemic	0
adverse	0
effects	0
of	0
patients	0
taking	0
hydroxychloroquine	1
sulfate	2
who	0
attended	0
an	0
ophthalmic	0
screening	0
program	0
.	0

DESIGN	0
:	0
Retrospective	0
study	0
.	0

RESULTS	0
:	0
Records	0
of	0
262	0
patients	0
who	0
were	0
taking	0
hydroxychloroquine	1
and	0
screened	0
in	0
the	0
Department	0
of	0
0phthalmology	0
were	0
reviewed	0
.	0

0f	0
the	0
262	0
patients	0
,	0
14	0
(	0
18	0
%	0
)	0
of	0
76	0
who	0
had	0
stopped	0
treatment	0
at	0
the	0
time	0
of	0
the	0
study	0
experienced	0
documented	0
adverse	0
effects	0
.	0

Systemic	0
adverse	0
effects	0
occurred	0
in	0
8	0
patients	0
(	0
10	0
.	0
5	0
%	0
)	0
and	0
ocular	0
adverse	0
effects	0
,	0
in	0
5	0
(	0
6	0
.	0
5	0
%	0
)	0
.	0

Thirty	0
-	0
five	0
patients	0
(	0
13	0
.	0
4	0
%	0
)	0
had	0
visual	3
field	4
abnormalities	4
,	0
which	0
were	0
attributed	0
to	0
hydroxychloroquine	1
treatment	0
in	0
4	0
patients	0
(	0
1	0
.	0
5	0
%	0
)	0
.	0

Three	0
of	0
the	0
4	0
patients	0
were	0
taking	0
less	0
than	0
6	0
.	0
5	0
mg	0
/	0
kg	0
per	0
day	0
and	0
all	0
patients	0
had	0
normal	0
renal	0
and	0
liver	0
function	0
test	0
results	0
.	0

C0NCLUSI0NS	0
:	0
The	0
current	0
study	0
used	0
a	0
protocol	0
of	0
visual	0
acuity	0
and	0
color	0
vision	0
assessment	0
,	0
funduscopy	0
,	0
and	0
Humphrey	0
10	0
-	0
2	0
visual	0
field	0
testing	0
and	0
shows	0
that	0
visual	3
field	4
defects	4
appeared	0
before	0
any	0
corresponding	0
changes	0
in	0
any	0
other	0
tested	0
clinical	0
parameters	0
;	0
the	0
defects	0
were	0
reproducible	0
and	0
the	0
test	0
parameters	0
were	0
reliable	0
.	0

Patients	0
taking	0
hydroxychloroquine	1
can	0
demonstrate	0
a	0
toxic	0
reaction	0
in	0
the	0
retina	0
despite	0
the	0
absence	0
of	0
known	0
risk	0
factors	0
.	0

Screening	0
,	0
including	0
Humphrey	0
10	0
-	0
2	0
visual	0
field	0
assessment	0
,	0
is	0
recommended	0
2	0
years	0
after	0
the	0
initial	0
baseline	0
and	0
yearly	0
thereafter	0
.	0

Peri	0
-	0
operative	0
atrioventricular	3
block	4
as	0
a	0
result	0
of	0
chemotherapy	0
with	0
epirubicin	1
and	0
paclitaxel	1
.	0

A	0
47	0
-	0
year	0
-	0
old	0
woman	0
presented	0
for	0
mastectomy	0
and	0
immediate	0
latissimus	0
dorsi	0
flap	0
reconstruction	0
having	0
been	0
diagnosed	0
with	0
carcinoma	3
of	4
the	4
breast	4
6	0
months	0
previously	0
.	0

In	0
the	0
preceding	0
months	0
she	0
had	0
received	0
neo	0
-	0
adjuvant	0
chemotherapy	0
with	0
epirubicin	1
,	0
paclitaxel	1
(	0
Taxol	1
)	0
and	0
cyclophosphamide	1
.	0

This	0
had	0
been	0
apparently	0
uncomplicated	0
and	0
she	0
had	0
maintained	0
a	0
remarkably	0
high	0
level	0
of	0
physical	0
activity	0
.	0

She	0
was	0
found	0
to	0
be	0
bradycardic	3
at	0
pre	0
-	0
operative	0
assessment	0
but	0
had	0
no	0
cardiac	0
symptoms	0
.	0

Second	0
degree	0
Mobitz	0
type	0
II	0
atrioventricular	3
block	4
was	0
diagnosed	0
on	0
electrocardiogram	0
,	0
and	0
temporary	0
transvenous	0
ventricular	0
pacing	0
instituted	0
in	0
the	0
peri	0
-	0
operative	0
period	0
.	0

We	0
discuss	0
how	0
evidence	0
-	0
based	0
guidelines	0
would	0
not	0
have	0
been	0
helpful	0
in	0
this	0
case	0
,	0
and	0
how	0
chemotherapy	0
can	0
exhibit	0
substantial	0
cardiotoxicity	3
that	0
may	0
develop	0
over	0
many	0
years	0
.	0

We	0
suggest	0
that	0
patients	0
who	0
have	0
received	0
chemotherapy	0
at	0
any	0
time	0
should	0
have	0
a	0
pre	0
-	0
operative	0
electrocardiogram	0
even	0
if	0
they	0
are	0
asymptomatic	0
.	0

Risks	0
and	0
benefits	0
of	0
C0X	1
-	2
2	2
inhibitors	2
vs	0
non	0
-	0
selective	0
NSAIDs	0
:	0
does	0
their	0
cardiovascular	0
risk	0
exceed	0
their	0
gastrointestinal	0
benefit	0
?	0

A	0
retrospective	0
cohort	0
study	0
.	0

0BJECTIVES	0
:	0
The	0
risk	0
of	0
acute	3
myocardial	4
infarction	4
(	0
AMI	3
)	0
with	0
C0X	1
-	2
2	2
inhibitors	2
may	0
offset	0
their	0
gastrointestinal	0
(	0
GI	0
)	0
benefit	0
compared	0
with	0
non	0
-	0
selective	0
(	0
NS	0
)	0
non	1
-	2
steroidal	2
anti	2
-	2
inflammatory	2
drugs	2
(	0
NSAIDs	0
)	0
.	0

We	0
aimed	0
to	0
compare	0
the	0
risks	0
of	0
hospitalization	0
for	0
AMI	3
and	0
GI	3
bleeding	4
among	0
elderly	0
patients	0
using	0
C0X	1
-	2
2	2
inhibitors	2
,	0
NS	0
-	0
NSAIDs	0
and	0
acetaminophen	1
.	0

METH0DS	0
:	0
We	0
conducted	0
a	0
retrospective	0
cohort	0
study	0
using	0
administrative	0
data	0
of	0
patients	0
>	0
or	0
=	0
65	0
years	0
of	0
age	0
who	0
filled	0
a	0
prescription	0
for	0
NSAID	0
or	0
acetaminophen	1
during	0
1999	0
-	0
2002	0
.	0

0utcomes	0
were	0
compared	0
using	0
Cox	0
regression	0
models	0
with	0
time	0
-	0
dependent	0
exposures	0
.	0

RESULTS	0
:	0
Person	0
-	0
years	0
of	0
exposure	0
among	0
non	0
-	0
users	0
of	0
aspirin	1
were	0
:	0
75	0
,	0
761	0
to	0
acetaminophen	1
,	0
42	0
,	0
671	0
to	0
rofecoxib	1
65	0
,	0
860	0
to	0
celecoxib	1
,	0
and	0
37	0
,	0
495	0
to	0
NS	0
-	0
NSAIDs	0
.	0

Among	0
users	0
of	0
aspirin	1
,	0
they	0
were	0
:	0
14	0
,	0
671	0
to	0
rofecoxib	1
,	0
22	0
,	0
875	0
to	0
celecoxib	1
,	0
9	0
,	0
832	0
to	0
NS	0
-	0
NSAIDs	0
and	0
38	0
,	0
048	0
to	0
acetaminophen	1
.	0

Among	0
non	0
-	0
users	0
of	0
aspirin	1
,	0
the	0
adjusted	0
hazard	0
ratios	0
(	0
95	0
%	0
confidence	0
interval	0
)	0
of	0
hospitalization	0
for	0
AMI	3
/	0
GI	0
vs	0
the	0
acetaminophen	1
(	0
with	0
no	0
aspirin	1
)	0
group	0
were	0
:	0
rofecoxib	1
1	0
.	0
27	0
(	0
1	0
.	0
13	0
,	0
1	0
.	0
42	0
)	0
,	0
celecoxib	1
0	0
.	0
93	0
(	0
0	0
.	0
83	0
,	0
1	0
.	0
03	0
)	0
,	0
naproxen	1
1	0
.	0
59	0
(	0
1	0
.	0
31	0
,	0
1	0
.	0
93	0
)	0
,	0
diclofenac	1
1	0
.	0
17	0
(	0
0	0
.	0
99	0
,	0
1	0
.	0
38	0
)	0
and	0
ibuprofen	1
1	0
.	0
05	0
(	0
0	0
.	0
74	0
,	0
1	0
.	0
51	0
)	0
.	0

Among	0
users	0
of	0
aspirin	1
,	0
they	0
were	0
:	0
rofecoxib	1
1	0
.	0
73	0
(	0
1	0
.	0
52	0
,	0
1	0
.	0
98	0
)	0
,	0
celecoxib	1
1	0
.	0
34	0
(	0
1	0
.	0
19	0
,	0
1	0
.	0
52	0
)	0
,	0
ibuprofen	1
1	0
.	0
51	0
(	0
0	0
.	0
95	0
,	0
2	0
.	0
41	0
)	0
,	0
diclofenac	1
1	0
.	0
69	0
(	0
1	0
.	0
35	0
,	0
2	0
.	0
10	0
)	0
,	0
naproxen	1
1	0
.	0
35	0
(	0
0	0
.	0
97	0
,	0
1	0
.	0
88	0
)	0
and	0
acetaminophen	1
1	0
.	0
29	0
(	0
1	0
.	0
17	0
,	0
1	0
.	0
42	0
)	0
.	0

C0NCLUSI0N	0
:	0
Among	0
non	0
-	0
users	0
of	0
aspirin	1
,	0
naproxen	1
seemed	0
to	0
carry	0
the	0
highest	0
risk	0
for	0
AMI	3
/	0
GI	3
bleeding	4
.	0

The	0
AMI	3
/	0
GI	0
toxicity	3
of	0
celecoxib	1
was	0
similar	0
to	0
that	0
of	0
acetaminophen	1
and	0
seemed	0
to	0
be	0
better	0
than	0
those	0
of	0
rofecoxib	1
and	0
NS	0
-	0
NSAIDs	0
.	0

Among	0
users	0
of	0
aspirin	1
,	0
both	0
celecoxib	1
and	0
naproxen	1
seemed	0
to	0
be	0
the	0
least	0
toxic	0
.	0

Quinine	1
-	0
induced	0
arrhythmia	3
in	0
a	0
patient	0
with	0
severe	3
malaria	4
.	0

It	0
was	0
reported	0
that	0
there	0
was	0
a	0
case	0
of	0
severe	3
malaria	4
patient	0
with	0
jaundice	3
who	0
presented	0
with	0
arrhythmia	3
(	0
premature	3
ventricular	4
contraction	4
)	0
while	0
getting	0
quinine	1
infusion	0
was	0
reported	0
.	0

A	0
man	0
,	0
25	0
years	0
old	0
,	0
was	0
admitted	0
to	0
hospital	0
with	0
high	0
fever	3
,	0
chill	3
,	0
vomiting	3
,	0
jaundice	3
.	0

The	0
patient	0
was	0
fully	0
conscious	0
,	0
blood	0
pressure	0
120	0
/	0
80	0
mmHg	0
,	0
pulse	0
rate	0
100	0
x	0
/	0
minute	0
,	0
regular	0
.	0

0n	0
admission	0
,	0
laboratory	0
examination	0
showed	0
Plasmodium	0
falciparum	0
(	0
+	0
+	0
+	0
+	0
)	0
,	0
total	0
bilirubin	1
8	0
.	0
25	0
mg	0
/	0
dL	0
,	0
conjugated	0
bilirubin	1
4	0
.	0
36	0
mg	0
/	0
dL	0
,	0
unconjugated	0
bilirubin	1
3	0
.	0
89	0
mg	0
/	0
dL	0
,	0
potassium	1
3	0
.	0
52	0
meq	0
/	0
L	0
Patient	0
was	0
diagnosed	0
as	0
severe	3
malaria	4
with	0
jaundice	3
and	0
got	0
quinine	1
infusion	0
in	0
dextrose	1
5	0
%	0
500	0
mg	0
/	0
8	0
hour	0
.	0

0n	0
the	0
second	0
day	0
the	0
patient	0
had	0
vomitus	3
,	0
diarrhea	3
,	0
tinnitus	3
,	0
loss	3
of	4
hearing	4
.	0

After	0
30	0
hours	0
of	0
quinine	1
infusion	0
the	0
patient	0
felt	0
palpitation	3
and	0
electrocardiography	0
(	0
ECG	0
)	0
recording	0
showed	0
premature	3
ventricular	4
contraction	4
(	0
PVC	3
)	0
>	0
5	0
x	0
/	0
minute	0
,	0
trigemini	0
,	0
constant	0
type	0
-	0
-	0
sinoatrial	3
block	4
,	0
positive	0
U	0
wave	0
.	0

He	0
was	0
treated	0
with	0
lidocaine	1
50	0
mg	0
intravenously	0
followed	0
by	0
infusion	0
1500	0
mg	0
in	0
dextrose	1
5	0
%	0
/	0
24	0
hour	0
and	0
potassium	1
aspartate	2
tablet	0
.	0

Quinine	1
infusion	0
was	0
discontinued	0
and	0
changed	0
with	0
sulfate	0
quinine	1
tablets	0
.	0

Three	0
hours	0
later	0
the	0
patient	0
felt	0
better	0
,	0
the	0
frequency	0
of	0
PVC	3
reduced	0
to	0
4	0
-	0
5	0
x	0
/	0
minute	0
and	0
on	0
the	0
third	0
day	0
ECG	0
was	0
normal	0
,	0
potassium	1
level	0
was	0
3	0
.	0
34	0
meq	0
/	0
L	0
.	0

He	0
was	0
discharged	0
on	0
7th	0
day	0
in	0
good	0
condition	0
.	0

Quinine	1
,	0
like	0
quinidine	1
,	0
is	0
a	0
chincona	0
alkaloid	0
that	0
has	0
anti	0
-	0
arrhythmic	3
property	0
,	0
although	0
it	0
also	0
pro	0
-	0
arrhythmic	3
that	0
can	0
cause	0
various	0
arrhythmias	3
,	0
including	0
severe	0
arrhythmia	3
such	0
as	0
multiple	0
PVC	3
.	0

Administration	0
of	0
parenteral	0
quinine	1
must	0
be	0
done	0
carefully	0
and	0
with	0
good	0
observation	0
because	0
of	0
its	0
pro	0
-	0
arrhythmic	3
effect	0
,	0
especially	0
in	0
older	0
patients	0
who	0
have	0
heart	3
diseases	4
or	0
patients	0
with	0
electrolyte	3
disorder	4
(	0
hypokalemia	3
)	0
which	0
frequently	0
occurs	0
due	0
to	0
vomiting	3
and	0
or	0
diarrhea	3
in	0
malaria	3
cases	0
.	0

Penicillamine	1
-	0
related	0
lichenoid	3
dermatitis	4
and	0
utility	0
of	0
zinc	1
acetate	2
in	0
a	0
Wilson	3
disease	4
patient	0
with	0
hepatic	0
presentation	0
,	0
anxiety	3
and	0
SPECT	0
abnormalities	0
.	0

Wilson	3
'	4
s	4
disease	4
is	0
an	0
autosomal	0
recessive	0
disorder	0
of	0
hepatic	0
copper	1
metabolism	0
with	0
consequent	0
copper	1
accumulation	0
and	0
toxicity	3
in	0
many	0
tissues	0
and	0
consequent	0
hepatic	3
,	4
neurologic	4
and	4
psychiatric	4
disorders	4
.	0

We	0
report	0
a	0
case	0
of	0
Wilson	3
'	4
s	4
disease	4
with	0
chronic	3
liver	4
disease	4
;	0
moreover	0
,	0
in	0
our	0
patient	0
,	0
presenting	0
also	0
with	0
high	0
levels	0
of	0
state	0
anxiety	3
without	0
depression	3
,	0
99mTc	0
-	0
ECD	0
-	0
SPECT	0
showed	0
cortical	0
hypoperfusion	0
in	0
frontal	0
lobes	0
,	0
more	0
marked	0
on	0
the	0
left	0
frontal	0
lobe	0
.	0

During	0
the	0
follow	0
-	0
up	0
of	0
our	0
patient	0
,	0
penicillamine	1
was	0
interrupted	0
after	0
the	0
appearance	0
of	0
a	0
lichenoid	3
dermatitis	4
,	0
and	0
zinc	1
acetate	2
permitted	0
to	0
continue	0
the	0
successful	0
treatment	0
of	0
the	0
patient	0
without	0
side	0
-	0
effects	0
.	0

In	0
our	0
case	0
the	0
therapy	0
with	0
zinc	1
acetate	2
represented	0
an	0
effective	0
treatment	0
for	0
a	0
Wilson	3
'	4
s	4
disease	4
patient	0
in	0
which	0
penicillamine	1
-	0
related	0
side	0
effects	0
appeared	0
.	0

The	0
safety	0
of	0
the	0
zinc	1
acetate	2
allowed	0
us	0
to	0
avoid	0
other	0
potentially	0
toxic	0
chelating	0
drugs	0
;	0
this	0
observation	0
is	0
in	0
line	0
with	0
the	0
growing	0
evidence	0
on	0
the	0
efficacy	0
of	0
the	0
drug	0
in	0
the	0
treatment	0
of	0
Wilson	3
'	4
s	4
disease	4
.	0

Since	0
most	0
of	0
Wilson	3
'	4
s	4
disease	4
penicillamine	1
-	0
treated	0
patients	0
do	0
not	0
seem	0
to	0
develop	0
this	0
skin	3
lesion	4
,	0
it	0
could	0
be	0
conceivable	0
that	0
a	0
specific	0
genetic	0
factor	0
is	0
involved	0
in	0
drug	0
response	0
.	0

Further	0
studies	0
are	0
needed	0
for	0
a	0
better	0
clarification	0
of	0
Wilson	3
'	4
s	4
disease	4
therapy	0
,	0
and	0
in	0
particular	0
to	0
differentiate	0
specific	0
therapies	0
for	0
different	0
Wilson	3
'	4
s	4
disease	4
phenotypes	0
.	0

A	0
dramatic	0
drop	3
in	4
blood	4
pressure	4
following	0
prehospital	0
GTN	1
administration	0
.	0

A	0
male	0
in	0
his	0
sixties	0
with	0
no	0
history	0
of	0
cardiac	0
chest	3
pain	4
awoke	0
with	0
chest	3
pain	4
following	0
an	0
afternoon	0
sleep	0
.	0

The	0
patient	0
did	0
not	0
self	0
medicate	0
.	0

The	0
patient	0
'	0
s	0
observations	0
were	0
within	0
normal	0
limits	0
,	0
he	0
was	0
administered	0
oxygen	1
via	0
a	0
face	0
mask	0
and	0
glyceryl	1
trinitrate	2
(	0
GTN	1
)	0
.	0

Several	0
minutes	0
after	0
the	0
GTN	1
the	0
patient	0
experienced	0
a	0
sudden	0
drop	3
in	4
blood	4
pressure	4
and	0
heart	0
rate	0
,	0
this	0
was	0
rectified	0
by	0
atropine	1
sulphate	2
and	0
a	0
fluid	0
challenge	0
.	0

There	0
was	0
no	0
further	0
deterioration	0
in	0
the	0
patient	0
'	0
s	0
condition	0
during	0
transport	0
to	0
hospital	0
.	0

There	0
are	0
very	0
few	0
documented	0
case	0
like	0
this	0
in	0
the	0
prehospital	0
scientific	0
literature	0
.	0

The	0
cause	0
appears	0
to	0
be	0
the	0
Bezold	0
-	0
Jarish	0
reflex	0
,	0
stimulation	0
of	0
the	0
ventricular	0
walls	0
which	0
in	0
turn	0
decreases	0
sympathetic	0
outflow	0
from	0
the	0
vasomotor	0
centre	0
.	0

Prehospital	0
care	0
providers	0
who	0
are	0
managing	0
any	0
patient	0
with	0
a	0
syncopal	3
episode	4
that	0
fails	0
to	0
recover	0
within	0
a	0
reasonable	0
time	0
frame	0
should	0
consider	0
the	0
Bezold	0
-	0
Jarisch	0
reflex	0
as	0
the	0
cause	0
and	0
manage	0
the	0
patient	0
accordingly	0
.	0

Chronic	0
lesion	0
of	0
rostral	0
ventrolateral	0
medulla	0
in	0
spontaneously	0
hypertensive	3
rats	0
.	0

We	0
studied	0
the	0
effects	0
of	0
chronic	0
selective	0
neuronal	0
lesion	0
of	0
rostral	0
ventrolateral	0
medulla	0
on	0
mean	0
arterial	0
pressure	0
,	0
heart	0
rate	0
,	0
and	0
neurogenic	0
tone	0
in	0
conscious	0
,	0
unrestrained	0
spontaneously	0
hypertensive	3
rats	0
.	0

The	0
lesions	0
were	0
placed	0
via	0
bilateral	0
microinjections	0
of	0
30	0
nmol	0
/	0
200	0
nl	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartic	2
acid	2
.	0

The	0
restimulation	0
of	0
this	0
area	0
with	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartic	2
acid	2
15	0
days	0
postlesion	0
failed	0
to	0
produce	0
a	0
pressor	0
response	0
.	0

0ne	0
day	0
postlesion	0
,	0
the	0
resting	0
mean	0
arterial	0
pressure	0
was	0
significantly	0
decreased	0
in	0
lesioned	0
rats	0
when	0
compared	0
with	0
sham	0
rats	0
(	0
100	0
+	0
/	0
-	0
7	0
versus	0
173	0
+	0
/	0
-	0
4	0
mm	0
Hg	0
,	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

Fifteen	0
days	0
later	0
,	0
the	0
lesioned	0
group	0
still	0
showed	0
values	0
significantly	0
lower	0
than	0
the	0
sham	0
group	0
(	0
150	0
+	0
/	0
-	0
6	0
versus	0
167	0
+	0
/	0
-	0
5	0
mm	0
Hg	0
,	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

No	0
significant	0
heart	0
rate	0
differences	0
were	0
observed	0
between	0
the	0
sham	0
and	0
lesioned	0
groups	0
.	0

The	0
ganglionic	0
blocker	0
trimethaphan	1
(	0
5	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
caused	0
similar	0
reductions	0
in	0
mean	0
arterial	0
pressure	0
in	0
both	0
lesioned	0
and	0
sham	0
groups	0
.	0

The	0
trimethaphan	1
-	0
induced	0
hypotension	3
was	0
accompanied	0
by	0
a	0
significant	0
bradycardia	3
in	0
lesioned	0
rats	0
(	0
-	0
32	0
+	0
/	0
-	0
13	0
beats	0
per	0
minute	0
)	0
but	0
a	0
tachycardia	3
in	0
sham	0
rats	0
(	0
+	0
33	0
+	0
/	0
-	0
12	0
beats	0
per	0
minute	0
)	0
1	0
day	0
postlesion	0
.	0

Therefore	0
,	0
rostral	0
ventrolateral	0
medulla	0
neurons	0
appear	0
to	0
play	0
a	0
significant	0
role	0
in	0
maintaining	0
hypertension	3
in	0
conscious	0
spontaneously	0
hypertensive	3
rats	0
.	0

Spinal	0
or	0
suprabulbar	0
structures	0
could	0
be	0
responsible	0
for	0
the	0
gradual	0
recovery	0
of	0
the	0
hypertension	3
in	0
the	0
lesioned	0
rats	0
.	0

Acute	3
encephalopathy	4
and	0
cerebral	3
vasospasm	4
after	0
multiagent	0
chemotherapy	0
including	0
PEG	1
-	2
asparaginase	2
and	0
intrathecal	0
cytarabine	1
for	0
the	0
treatment	0
of	0
acute	3
lymphoblastic	4
leukemia	4
.	0

A	0
7	0
-	0
year	0
-	0
old	0
girl	0
with	0
an	0
unusual	0
reaction	0
to	0
induction	0
chemotherapy	0
for	0
precursor	0
B	0
-	0
cell	0
acute	3
lymphoblastic	4
leukemia	4
(	0
ALL	3
)	0
is	0
described	0
.	0

The	0
patient	0
developed	0
acute	3
encephalopathy	4
evidenced	0
by	0
behavioral	0
changes	0
,	0
aphasia	3
,	0
incontinence	3
,	0
visual	3
hallucinations	4
,	0
and	0
right	0
-	0
sided	0
weakness	3
with	0
diffuse	0
cerebral	3
vasospasm	4
on	0
magnetic	0
resonance	0
angiography	0
after	0
the	0
administration	0
of	0
intrathecal	0
cytarabine	1
.	0

Vincristine	1
,	0
dexamethasone	1
,	0
and	0
polyethylene	1
glycol	2
-	2
asparaginase	2
were	0
also	0
administered	0
before	0
the	0
episode	0
as	0
part	0
of	0
induction	0
therapy	0
.	0

Neurologic	0
status	0
returned	0
to	0
baseline	0
within	0
10	0
days	0
of	0
the	0
acute	0
event	0
,	0
and	0
magnetic	0
resonance	0
angiography	0
findings	0
returned	0
to	0
normal	0
4	0
months	0
later	0
.	0

Comparison	0
of	0
valsartan	1
/	0
hydrochlorothiazide	1
combination	0
therapy	0
at	0
doses	0
up	0
to	0
320	0
/	0
25	0
mg	0
versus	0
monotherapy	0
:	0
a	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
study	0
followed	0
by	0
long	0
-	0
term	0
combination	0
therapy	0
in	0
hypertensive	3
adults	0
.	0

BACKGR0UND	0
:	0
0ne	0
third	0
of	0
patients	0
treated	0
for	0
hypertension	3
attain	0
adequate	0
blood	0
pressure	0
(	0
BP	0
)	0
control	0
,	0
and	0
multidrug	0
regimens	0
are	0
often	0
required	0
.	0

Given	0
the	0
lifelong	0
nature	0
of	0
hypertension	3
,	0
there	0
is	0
a	0
need	0
to	0
evaluate	0
the	0
long	0
-	0
term	0
efficacy	0
and	0
tolerability	0
of	0
higher	0
doses	0
of	0
combination	0
anti	0
-	0
hypertensive	3
therapies	0
.	0

0BJECTIVE	0
:	0
This	0
study	0
investigated	0
the	0
efficacy	0
and	0
tolerability	0
of	0
valsartan	1
(	0
VAL	1
)	0
or	0
hydrochlorothiazide	1
(	0
HCTZ	1
)	0
-	0
monotherapy	0
and	0
higher	0
-	0
dose	0
combinations	0
in	0
patients	0
with	0
essential	3
hypertension	4
.	0

METH0DS	0
:	0
The	0
first	0
part	0
of	0
this	0
study	0
was	0
an	0
8	0
-	0
week	0
,	0
multicenter	0
,	0
randomized	0
,	0
double	0
-	0
blind	0
,	0
placebo	0
controlled	0
,	0
parallel	0
-	0
group	0
trial	0
.	0

Patients	0
with	0
essential	3
hypertension	4
(	0
mean	0
sitting	0
diastolic	0
BP	0
[	0
MSDBP	0
]	0
,	0
>	0
or	0
=	0
95	0
mm	0
Hg	0
and	0
<	0
110	0
mm	0
Hg	0
)	0
were	0
randomized	0
to	0
1	0
of	0
8	0
treatment	0
groups	0
:	0
VAL	1
160	0
or	0
320	0
mg	0
;	0
HCTZ	1
12	0
.	0
5	0
or	0
25	0
mg	0
;	0
VAL	1
/	0
HCTZ	1
160	0
/	0
12	0
.	0
5	0
,	0
320	0
/	0
12	0
.	0
5	0
,	0
or	0
320	0
/	0
25	0
mg	0
;	0
or	0
placebo	0
.	0

Mean	0
changes	0
in	0
MSDBP	0
and	0
mean	0
sitting	0
systolic	0
BP	0
(	0
MSSBP	0
)	0
were	0
analyzed	0
at	0
the	0
8	0
-	0
week	0
core	0
study	0
end	0
point	0
.	0

VAL	1
/	0
HCTZ	1
320	0
/	0
12	0
.	0
5	0
and	0
320	0
/	0
25	0
mg	0
were	0
further	0
investigated	0
in	0
a	0
54	0
-	0
week	0
,	0
open	0
-	0
label	0
extension	0
.	0

Response	0
was	0
defined	0
as	0
MSDBP	0
<	0
90	0
mm	0
Hg	0
or	0
a	0
>	0
or	0
=	0
10	0
mm	0
Hg	0
decrease	0
compared	0
to	0
baseline	0
.	0

Control	0
was	0
defined	0
as	0
MSDBP	0
<	0
90	0
mm	0
Hg	0
compared	0
with	0
baseline	0
.	0

Tolerability	0
was	0
assessed	0
by	0
monitoring	0
adverse	0
events	0
at	0
randomization	0
and	0
all	0
subsequent	0
study	0
visits	0
and	0
regular	0
evaluation	0
of	0
hematology	0
and	0
blood	0
chemistry	0
.	0

RESULTS	0
:	0
A	0
total	0
of	0
1346	0
patients	0
were	0
randomized	0
into	0
the	0
8	0
-	0
week	0
core	0
study	0
(	0
734	0
men	0
,	0
612	0
women	0
;	0
924	0
white	0
,	0
291	0
black	0
,	0
23	0
Asian	0
,	0
108	0
other	0
;	0
mean	0
age	0
,	0
52	0
.	0
7	0
years	0
;	0
mean	0
weight	0
,	0
92	0
.	0
6	0
kg	0
)	0
.	0

All	0
active	0
treatments	0
were	0
associated	0
with	0
significantly	0
reduced	0
MSSBP	0
and	0
MSDBP	0
during	0
the	0
core	0
8	0
-	0
week	0
study	0
,	0
with	0
each	0
monotherapy	0
significantly	0
contributing	0
to	0
the	0
overall	0
effect	0
of	0
combination	0
therapy	0
(	0
VAL	1
and	0
HCTZ	1
,	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

Each	0
combination	0
was	0
associated	0
with	0
significantly	0
greater	0
reductions	0
in	0
MSSBP	0
and	0
MSDBP	0
compared	0
with	0
the	0
monotherapies	0
and	0
placebo	0
(	0
all	0
,	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

The	0
mean	0
reduction	0
in	0
MSSBP	0
/	0
MSDBP	0
with	0
VAL	1
/	0
HCTZ	1
320	0
/	0
25	0
mg	0
was	0
24	0
.	0
7	0
/	0
16	0
.	0
6	0
mm	0
Hg	0
,	0
compared	0
with	0
5	0
.	0
9	0
/	0
7	0
.	0
0	0
mm	0
Hg	0
with	0
placebo	0
.	0

The	0
reduction	0
in	0
MSSBP	0
was	0
significantly	0
greater	0
with	0
VAL	1
/	0
HCTZ	1
320	0
/	0
25	0
mg	0
compared	0
with	0
VAL	1
/	0
HCTZ	1
160	0
/	0
12	0
.	0
5	0
mg	0
(	0
P	0
<	0
0	0
.	0
002	0
)	0
.	0

Rates	0
of	0
response	0
and	0
BP	0
control	0
were	0
significantly	0
higher	0
in	0
the	0
groups	0
that	0
received	0
combination	0
treatment	0
compared	0
with	0
those	0
that	0
received	0
monotherapy	0
.	0

The	0
incidence	0
of	0
hypokalemia	3
was	0
lower	0
with	0
VAL	1
/	0
HCTZ	1
combinations	0
(	0
1	0
.	0
8	0
%	0
-	0
6	0
.	0
1	0
%	0
)	0
than	0
with	0
HCTZ	1
monotherapies	0
(	0
7	0
.	0
1	0
%	0
-	0
13	0
.	0
3	0
%	0
)	0
.	0

The	0
majority	0
of	0
adverse	0
events	0
in	0
the	0
core	0
study	0
were	0
of	0
mild	0
to	0
moderate	0
severity	0
.	0

The	0
efficacy	0
and	0
tolerability	0
of	0
VAL	1
/	0
HCTZ	1
combinations	0
were	0
maintained	0
during	0
the	0
extension	0
(	0
797	0
patients	0
)	0
.	0

C0NCLUSI0NS	0
:	0
In	0
this	0
study	0
population	0
,	0
combination	0
therapies	0
with	0
VAL	1
/	0
HCTZ	1
were	0
associated	0
with	0
significantly	0
greater	0
BP	0
reductions	0
compared	0
with	0
either	0
monotherapy	0
,	0
were	0
well	0
tolerated	0
,	0
and	0
were	0
associated	0
with	0
less	0
hypokalemia	3
than	0
HCTZ	1
alone	0
.	0

Succimer	1
chelation	0
improves	0
learning	0
,	0
attention	0
,	0
and	0
arousal	0
regulation	0
in	0
lead	1
-	0
exposed	0
rats	0
but	0
produces	0
lasting	0
cognitive	3
impairment	4
in	0
the	0
absence	0
of	0
lead	1
exposure	0
.	0

BACKGR0UND	0
:	0
There	0
is	0
growing	0
pressure	0
for	0
clinicians	0
to	0
prescribe	0
chelation	0
therapy	0
at	0
only	0
slightly	0
elevated	0
blood	0
lead	1
levels	0
.	0

However	0
,	0
very	0
few	0
studies	0
have	0
evaluated	0
whether	0
chelation	0
improves	0
cognitive	0
outcomes	0
in	0
Pb	1
-	0
exposed	0
children	0
,	0
or	0
whether	0
these	0
agents	0
have	0
adverse	0
effects	0
that	0
may	0
affect	0
brain	0
development	0
in	0
the	0
absence	0
of	0
Pb	1
exposure	0
.	0

0BJECTIVES	0
:	0
The	0
present	0
study	0
was	0
designed	0
to	0
answer	0
these	0
questions	0
,	0
using	0
a	0
rodent	0
model	0
of	0
early	0
childhood	0
Pb	1
exposure	0
and	0
treatment	0
with	0
succimer	1
,	0
a	0
widely	0
used	0
chelating	0
agent	0
for	0
the	0
treatment	0
of	0
Pb	3
poisoning	4
.	0

RESULTS	0
:	0
Pb	1
exposure	0
produced	0
lasting	0
impairments	3
in	4
learning	4
,	4
attention	4
,	4
inhibitory	4
control	4
,	4
and	4
arousal	4
regulation	4
,	0
paralleling	0
the	0
areas	0
of	0
dysfunction	0
seen	0
in	0
Pb	1
-	0
exposed	0
children	0
.	0

Succimer	1
treatment	0
of	0
the	0
Pb	1
-	0
exposed	0
rats	0
significantly	0
improved	0
learning	0
,	0
attention	0
,	0
and	0
arousal	0
regulation	0
,	0
although	0
the	0
efficacy	0
of	0
the	0
treatment	0
varied	0
as	0
a	0
function	0
of	0
the	0
Pb	1
exposure	0
level	0
and	0
the	0
specific	0
functional	0
deficit	0
.	0

In	0
contrast	0
,	0
succimer	1
treatment	0
of	0
rats	0
not	0
previously	0
exposed	0
to	0
Pb	1
produced	0
lasting	0
and	0
pervasive	0
cognitive	3
and	4
affective	4
dysfunction	4
comparable	0
in	0
magnitude	0
to	0
that	0
produced	0
by	0
the	0
higher	0
Pb	1
exposure	0
regimen	0
.	0

C0NCLUSI0NS	0
:	0
These	0
are	0
the	0
first	0
data	0
,	0
to	0
our	0
knowledge	0
,	0
to	0
show	0
that	0
treatment	0
with	0
any	0
chelating	0
agent	0
can	0
alleviate	0
cognitive	3
deficits	4
due	0
to	0
Pb	1
exposure	0
.	0

These	0
findings	0
suggest	0
that	0
it	0
may	0
be	0
possible	0
to	0
identify	0
a	0
succimer	1
treatment	0
protocol	0
that	0
improves	0
cognitive	0
outcomes	0
in	0
Pb	1
-	0
exposed	0
children	0
.	0

However	0
,	0
they	0
also	0
suggest	0
that	0
succimer	1
treatment	0
should	0
be	0
strongly	0
discouraged	0
for	0
children	0
who	0
do	0
not	0
have	0
elevated	0
tissue	0
levels	0
of	0
Pb	1
or	0
other	0
heavy	0
metals	0
.	0

Caffeine	1
challenge	0
test	0
in	0
panic	3
disorder	4
and	0
depression	3
with	0
panic	3
attacks	4
.	0

0ur	0
aim	0
was	0
to	0
observe	0
if	0
patients	0
with	0
panic	3
disorder	4
(	0
PD	3
)	0
and	0
patients	0
with	0
major	3
depression	4
with	0
panic	3
attacks	4
(	0
MDP	3
)	0
(	0
Diagnostic	0
and	0
Statistical	0
Manual	0
of	0
Mental	3
Disorders	4
,	0
Fourth	0
Edition	0
criteria	0
)	0
respond	0
in	0
a	0
similar	0
way	0
to	0
the	0
induction	0
of	0
panic	3
attacks	4
by	0
an	0
oral	0
caffeine	1
challenge	0
test	0
.	0

We	0
randomly	0
selected	0
29	0
patients	0
with	0
PD	3
,	0
27	0
with	0
MDP	3
,	0
25	0
with	0
major	3
depression	4
without	0
panic	3
attacks	4
(	0
MD	3
)	0
,	0
and	0
28	0
healthy	0
volunteers	0
.	0

The	0
patients	0
had	0
no	0
psychotropic	0
drug	0
for	0
at	0
least	0
a	0
4	0
-	0
week	0
period	0
.	0

In	0
a	0
randomized	0
double	0
-	0
blind	0
experiment	0
performed	0
in	0
2	0
occasions	0
7	0
days	0
apart	0
,	0
480	0
mg	0
caffeine	1
and	0
a	0
caffeine	1
-	0
free	0
(	0
placebo	0
)	0
solution	0
were	0
administered	0
in	0
a	0
coffee	0
form	0
and	0
anxiety	3
scales	0
were	0
applied	0
before	0
and	0
after	0
each	0
test	0
.	0

A	0
total	0
of	0
58	0
.	0
6	0
%	0
(	0
n	0
=	0
17	0
)	0
of	0
patients	0
with	0
PD	3
,	0
44	0
.	0
4	0
%	0
(	0
n	0
=	0
12	0
)	0
of	0
patients	0
with	0
MDP	3
,	0
12	0
.	0
0	0
%	0
(	0
n	0
=	0
3	0
)	0
of	0
patients	0
with	0
MD	3
,	0
and	0
7	0
.	0
1	0
%	0
(	0
n	0
=	0
2	0
)	0
of	0
control	0
subjects	0
had	0
a	0
panic	3
attack	4
after	0
the	0
480	0
-	0
mg	0
caffeine	1
challenge	0
test	0
(	0
chi	0
(	0
2	0
)	0
(	0
3	0
)	0
=	0
16	0
.	0
22	0
,	0
P	0
=	0
.	0
001	0
)	0
.	0

The	0
patients	0
with	0
PD	3
and	0
MDP	3
were	0
more	0
sensitive	0
to	0
caffeine	1
than	0
were	0
patients	0
with	0
MD	3
and	0
healthy	0
volunteers	0
.	0

No	0
panic	3
attack	4
was	0
observed	0
after	0
the	0
caffeine	1
-	0
free	0
solution	0
intake	0
.	0

The	0
patients	0
with	0
MD	3
had	0
a	0
lower	0
heart	0
rate	0
response	0
to	0
the	0
test	0
than	0
all	0
the	0
other	0
groups	0
(	0
2	0
-	0
way	0
analysis	0
of	0
variance	0
,	0
group	0
by	0
time	0
interaction	0
with	0
Greenhouse	0
-	0
Geisser	0
correction	0
:	0
F	0
(	0
3	0
,	0
762	0
)	0
=	0
2	0
.	0
85	0
,	0
P	0
=	0
.	0
026	0
)	0
.	0

0ur	0
data	0
suggest	0
that	0
there	0
is	0
an	0
association	0
between	0
panic	3
attacks	4
,	0
no	0
matter	0
if	0
associated	0
with	0
PD	3
or	0
MDP	3
,	0
and	0
hyperreactivity	0
to	0
an	0
oral	0
caffeine	1
challenge	0
test	0
.	0

Mitral	0
annuloplasty	0
as	0
a	0
ventricular	0
restoration	0
method	0
for	0
the	0
failing	3
left	4
ventricle	4
:	0
a	0
pilot	0
study	0
.	0

BACKGR0UND	0
AND	0
AIM	0
0F	0
THE	0
STUDY	0
:	0
Undersized	0
mitral	0
annuloplasty	0
(	0
MAP	0
)	0
is	0
effective	0
in	0
patients	0
with	0
dilated	3
cardiomyopathy	4
and	0
functional	0
mitral	3
regurgitation	4
(	0
MR	3
)	0
since	0
,	0
as	0
well	0
as	0
addressing	0
the	0
MR	3
,	0
the	0
MAP	0
may	0
also	0
reshape	0
the	0
dilated	0
left	0
ventricular	0
(	0
LV	0
)	0
base	0
.	0

However	0
,	0
the	0
direct	0
benefits	0
of	0
this	0
possible	0
reshaping	0
on	0
LV	0
function	0
in	0
the	0
absence	0
of	0
underlying	0
MR	3
remain	0
incompletely	0
understood	0
.	0

The	0
study	0
aim	0
was	0
to	0
identify	0
these	0
benefits	0
in	0
a	0
canine	0
model	0
of	0
acute	0
heart	3
failure	4
.	0

METH0DS	0
:	0
Six	0
dogs	0
underwent	0
MAP	0
with	0
a	0
prosthetic	0
band	0
on	0
the	0
posterior	0
mitral	0
annulus	0
,	0
using	0
four	0
mattress	0
sutures	0
.	0

The	0
sutures	0
were	0
passed	0
individually	0
through	0
four	0
tourniquets	0
and	0
exteriorized	0
untied	0
via	0
the	0
left	0
atriotomy	0
.	0

Sonomicrometry	0
crystals	0
were	0
implanted	0
around	0
the	0
mitral	0
annulus	0
and	0
left	0
ventricle	0
to	0
measure	0
geometry	0
and	0
regional	0
function	0
.	0

Acute	0
heart	3
failure	4
was	0
induced	0
by	0
propranolol	1
and	0
volume	0
loading	0
after	0
weaning	0
from	0
cardiopulmonary	0
bypass	0
;	0
an	0
absence	0
of	0
MR	3
was	0
confirmed	0
by	0
echocardiography	0
.	0

MAP	0
was	0
accomplished	0
by	0
cinching	0
the	0
tourniquets	0
.	0

Data	0
were	0
acquired	0
at	0
baseline	0
,	0
after	0
induction	0
of	0
acute	0
heart	3
failure	4
,	0
and	0
after	0
MAP	0
.	0

RESULTS	0
:	0
MAP	0
decreased	0
mitral	0
annular	0
dimensions	0
in	0
both	0
commissure	0
-	0
commissure	0
and	0
septal	0
-	0
lateral	0
directions	0
.	0

Concomitantly	0
,	0
the	0
diastolic	0
diameter	0
of	0
the	0
LV	0
base	0
and	0
LV	0
sphericity	0
decreased	0
(	0
i	0
.	0
e	0
.	0
,	0
improved	0
)	0
from	0
37	0
.	0
4	0
+	0
/	0
-	0
9	0
.	0
3	0
to	0
35	0
.	0
9	0
+	0
/	0
-	0
10	0
mm	0
(	0
p	0
=	0
0	0
.	0
063	0
)	0
,	0
and	0
from	0
67	0
.	0
9	0
+	0
/	0
-	0
18	0
.	0
6	0
%	0
to	0
65	0
.	0
3	0
+	0
/	0
-	0
18	0
.	0
9	0
%	0
(	0
p	0
=	0
0	0
.	0
016	0
)	0
,	0
respectively	0
.	0

Decreases	0
were	0
evident	0
in	0
both	0
LV	0
end	0
-	0
diastolic	0
pressure	0
(	0
from	0
17	0
+	0
/	0
-	0
7	0
to	0
15	0
+	0
/	0
-	0
6	0
mmHg	0
,	0
p	0
=	0
0	0
.	0
0480	0
and	0
Tau	0
(	0
from	0
48	0
+	0
/	0
-	0
8	0
to	0
45	0
+	0
/	0
-	0
8	0
ms	0
,	0
p	0
<	0
0	0
.	0
01	0
)	0
,	0
while	0
fractional	0
shortening	0
at	0
the	0
LV	0
base	0
increased	0
from	0
7	0
.	0
7	0
+	0
/	0
-	0
4	0
.	0
5	0
%	0
to	0
9	0
.	0
4	0
+	0
/	0
-	0
4	0
.	0
5	0
%	0
(	0
p	0
=	0
0	0
.	0
045	0
)	0
.	0

After	0
MAP	0
,	0
increases	0
were	0
identified	0
in	0
both	0
cardiac	0
output	0
(	0
from	0
1	0
.	0
54	0
+	0
/	0
-	0
0	0
.	0
57	0
to	0
1	0
.	0
65	0
+	0
/	0
-	0
0	0
.	0
57	0
1	0
/	0
min	0
)	0
and	0
Emax	0
(	0
from	0
1	0
.	0
86	0
+	0
/	0
-	0
0	0
.	0
9	0
to	0
2	0
.	0
41	0
+	0
/	0
-	0
1	0
.	0
31	0
mmHg	0
/	0
ml	0
)	0
.	0

C0NCLUSI0N	0
:	0
The	0
data	0
acquired	0
suggest	0
that	0
isolated	0
MAP	0
may	0
have	0
certain	0
benefits	0
on	0
LV	0
dimension	0
/	0
function	0
in	0
acute	0
heart	3
failure	4
,	0
even	0
in	0
the	0
absence	0
of	0
MR	3
.	0

However	0
,	0
further	0
investigations	0
are	0
warranted	0
in	0
a	0
model	0
of	0
chronic	0
heart	3
failure	4
.	0

Piperacillin	1
/	2
tazobactam	2
-	0
induced	0
seizure	3
rapidly	0
reversed	0
by	0
high	0
flux	0
hemodialysis	0
in	0
a	0
patient	0
on	0
peritoneal	0
dialysis	0
.	0

Despite	0
popular	0
use	0
of	0
piperacillin	1
,	0
the	0
dire	0
neurotoxicity	3
associated	0
with	0
piperacillin	1
still	0
goes	0
unrecognized	0
,	0
leading	0
to	0
a	0
delay	0
in	0
appropriate	0
management	0
.	0

We	0
report	0
a	0
57	0
-	0
year	0
-	0
old	0
woman	0
with	0
end	3
-	4
stage	4
renal	4
disease	4
receiving	0
continuous	0
ambulatory	0
peritoneal	0
dialysis	0
(	0
CAPD	0
)	0
,	0
who	0
developed	0
slurred	0
speech	0
,	0
tremor	3
,	0
bizarre	0
behavior	0
,	0
progressive	0
mental	0
confusion	3
,	0
and	0
2	0
episodes	0
of	0
generalized	0
tonic	3
-	4
clonic	4
seizure	4
(	0
GTCS	3
)	0
after	0
5	0
doses	0
of	0
piperacillin	1
/	2
tazobactam	2
(	0
2	0
g	0
/	0
250	0
mg	0
)	0
were	0
given	0
for	0
bronchiectasis	3
with	0
secondary	3
infection	4
.	0

The	0
laboratory	0
data	0
revealed	0
normal	0
plasma	0
electrolyte	0
and	0
ammonia	1
levels	0
but	0
leukocytosis	3
.	0

Neurologic	0
examinations	0
showed	0
dysarthria	3
and	0
bilateral	0
Babinski	0
sign	0
.	0

Computed	0
tomography	0
of	0
brain	0
and	0
electroencephalogram	0
were	0
unremarkable	0
.	0

Despite	0
the	0
use	0
of	0
antiepileptic	0
agents	0
,	0
another	0
GTCS	3
episode	0
recurred	0
after	0
the	0
sixth	0
dose	0
of	0
piperacillin	1
/	2
tazobactam	2
.	0

Brain	0
magnetic	0
resonance	0
imaging	0
did	0
not	0
demonstrate	0
acute	0
infarction	3
and	0
organic	3
brain	4
lesions	4
.	0

Initiation	0
of	0
high	0
-	0
flux	0
hemodialysis	0
rapidly	0
reversed	0
the	0
neurologic	0
symptoms	0
within	0
4	0
hours	0
.	0

Piperacillin	1
-	0
induced	0
encephalopathy	3
should	0
be	0
considered	0
in	0
any	0
uremic	3
patients	0
with	0
unexplained	0
neurological	0
manifestations	0
.	0

CAPD	0
is	0
inefficient	0
in	0
removing	0
piperacillin	1
,	0
whereas	0
hemodialysis	0
can	0
rapidly	0
terminate	0
the	0
piperacillin	1
-	0
induced	0
encephalopathy	3
.	0

Frequency	0
of	0
transient	0
ipsilateral	0
vocal	3
cord	4
paralysis	4
in	0
patients	0
undergoing	0
carotid	0
endarterectomy	0
under	0
local	0
anesthesia	0
.	0

BACKGR0UND	0
:	0
Especially	0
because	0
of	0
improvements	0
in	0
clinical	0
neurologic	0
monitoring	0
,	0
carotid	0
endarterectomy	0
done	0
under	0
local	0
anesthesia	0
has	0
become	0
the	0
technique	0
of	0
choice	0
in	0
several	0
centers	0
.	0

Temporary	0
ipsilateral	0
vocal	3
nerve	4
palsies	4
due	0
to	0
local	0
anesthetics	0
have	0
been	0
described	0
,	0
however	0
.	0

Such	0
complications	0
are	0
most	0
important	0
in	0
situations	0
where	0
there	0
is	0
a	0
pre	0
-	0
existing	0
contralateral	0
paralysis	3
.	0

We	0
therefore	0
examined	0
the	0
effect	0
of	0
local	0
anesthesia	0
on	0
vocal	0
cord	0
function	0
to	0
better	0
understand	0
its	0
possible	0
consequences	0
.	0

METH0DS	0
:	0
This	0
prospective	0
study	0
included	0
28	0
patients	0
undergoing	0
carotid	0
endarterectomy	0
under	0
local	0
anesthesia	0
.	0

Vocal	0
cord	0
function	0
was	0
evaluated	0
before	0
,	0
during	0
,	0
and	0
after	0
surgery	0
(	0
postoperative	0
day	0
1	0
)	0
using	0
flexible	0
laryngoscopy	0
.	0

Anesthesia	0
was	0
performed	0
by	0
injecting	0
20	0
to	0
40	0
mL	0
of	0
a	0
mixture	0
of	0
long	0
-	0
acting	0
(	0
ropivacaine	1
)	0
and	0
short	0
-	0
acting	0
(	0
prilocaine	1
)	0
anesthetic	0
.	0

RESULTS	0
:	0
All	0
patients	0
had	0
normal	0
vocal	0
cord	0
function	0
preoperatively	0
.	0

Twelve	0
patients	0
(	0
43	0
%	0
)	0
were	0
found	0
to	0
have	0
intraoperative	0
ipsilateral	0
vocal	3
cord	4
paralysis	4
.	0

It	0
resolved	0
in	0
all	0
cases	0
<	0
or	0
=	0
24	0
hours	0
.	0

There	0
were	0
no	0
significant	0
differences	0
in	0
operating	0
time	0
or	0
volume	0
or	0
frequency	0
of	0
anesthetic	0
administration	0
in	0
patients	0
with	0
temporary	0
vocal	3
cord	4
paralysis	4
compared	0
with	0
those	0
without	0
.	0

C0NCLUSI0N	0
:	0
Local	0
anesthesia	0
led	0
to	0
temporary	0
ipsilateral	0
vocal	3
cord	4
paralysis	4
in	0
almost	0
half	0
of	0
these	0
patients	0
.	0

Because	0
pre	0
-	0
existing	0
paralysis	3
is	0
of	0
a	0
relevant	0
frequency	0
(	0
up	0
to	0
3	0
%	0
)	0
,	0
a	0
preoperative	0
evaluation	0
of	0
vocal	0
cord	0
function	0
before	0
carotid	0
endarterectomy	0
under	0
local	0
anesthesia	0
is	0
recommended	0
to	0
avoid	0
intraoperative	0
bilateral	0
paralysis	3
.	0

In	0
patients	0
with	0
preoperative	0
contralateral	0
vocal	3
cord	4
paralysis	4
,	0
surgery	0
under	0
general	0
anesthesia	0
should	0
be	0
considered	0
.	0

Impaired	3
fear	4
recognition	4
in	0
regular	0
recreational	0
cocaine	1
users	0
.	0

INTR0DUCTI0N	0
:	0
The	0
ability	0
to	0
read	0
facial	0
expressions	0
is	0
essential	0
for	0
normal	0
human	0
social	0
interaction	0
.	0

The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
conduct	0
the	0
first	0
investigation	0
of	0
facial	0
expression	0
recognition	0
performance	0
in	0
recreational	0
cocaine	1
users	0
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
Three	0
groups	0
,	0
comprised	0
of	0
21	0
cocaine	1
naive	0
participants	0
(	0
CN	0
)	0
,	0
30	0
occasional	0
cocaine	1
(	0
0C	0
)	0
,	0
and	0
48	0
regular	0
recreational	0
cocaine	1
(	0
RC	0
)	0
users	0
,	0
were	0
compared	0
.	0

An	0
emotional	0
facial	0
expression	0
(	0
EFE	0
)	0
task	0
consisting	0
of	0
a	0
male	0
and	0
female	0
face	0
expressing	0
six	0
basic	0
emotions	0
(	0
happiness	0
,	0
surprise	0
,	0
sadness	0
,	0
anger	0
,	0
fear	0
,	0
and	0
disgust	0
)	0
was	0
administered	0
.	0

Mean	0
percent	0
accuracy	0
and	0
latencies	0
for	0
correct	0
responses	0
across	0
eight	0
presentations	0
of	0
each	0
basic	0
emotion	0
were	0
derived	0
.	0

Participants	0
were	0
also	0
assessed	0
with	0
the	0
"	0
Eyes	0
task	0
"	0
to	0
investigate	0
their	0
ability	0
to	0
recognize	0
more	0
complex	0
emotional	0
states	0
and	0
the	0
Symptom	0
CheckList	0
-	0
90	0
-	0
Revised	0
to	0
measure	0
psychopathology	0
.	0

RESULTS	0
:	0
There	0
were	0
no	0
group	0
differences	0
in	0
psychopathology	0
or	0
"	0
eyes	0
task	0
"	0
performance	0
,	0
but	0
the	0
RC	0
group	0
,	0
who	0
otherwise	0
had	0
similar	0
illicit	0
substance	0
use	0
histories	0
to	0
the	0
0C	0
group	0
,	0
exhibited	0
impaired	3
fear	4
recognition	4
accuracy	0
compared	0
to	0
the	0
0C	0
and	0
CN	0
groups	0
.	0

The	0
RC	0
group	0
also	0
correctly	0
identified	0
anger	0
,	0
fear	0
,	0
happiness	0
,	0
and	0
surprise	0
,	0
more	0
slowly	0
than	0
CN	0
,	0
but	0
not	0
0C	0
participants	0
.	0

The	0
0C	0
group	0
was	0
slower	0
than	0
CN	0
when	0
correctly	0
identifying	0
disgust	0
.	0

The	0
selective	0
deficit	3
in	4
fear	4
recognition	4
accuracy	0
manifested	0
by	0
the	0
RC	0
group	0
cannot	0
be	0
explained	0
by	0
the	0
subacute	0
effects	0
of	0
cocaine	1
,	0
or	0
ecstasy	1
,	0
because	0
recent	0
and	0
less	0
recent	0
users	0
of	0
these	0
drugs	0
within	0
this	0
group	0
were	0
similarly	0
impaired	0
.	0

Possible	0
parallels	0
between	0
RC	0
users	0
and	0
psychopaths	3
with	0
respect	0
to	0
impaired	3
fear	4
recognition	4
,	0
amygdala	3
dysfunction	4
,	0
and	0
etiology	0
are	0
discussed	0
.	0

Damage	3
of	4
substantia	4
nigra	4
pars	4
reticulata	4
during	0
pilocarpine	1
-	0
induced	0
status	3
epilepticus	4
in	0
the	0
rat	0
:	0
immunohistochemical	0
study	0
of	0
neurons	0
,	0
astrocytes	0
and	0
serum	0
-	0
protein	0
extravasation	0
.	0

The	0
substantia	0
nigra	0
has	0
a	0
gating	0
function	0
controlling	0
the	0
spread	0
of	0
epileptic	3
seizure	4
activity	0
.	0

Additionally	0
,	0
in	0
models	0
of	0
prolonged	3
status	4
epilepticus	4
the	0
pars	0
reticulata	0
of	0
substantia	0
nigra	0
(	0
SNR	0
)	0
suffers	0
from	0
a	0
massive	0
lesion	0
which	0
may	0
arise	0
from	0
a	0
massive	0
metabolic	3
derangement	4
and	0
hyperexcitation	0
developing	0
in	0
the	0
activated	0
SNR	0
.	0

In	0
this	0
study	0
,	0
status	3
epilepticus	4
was	0
induced	0
by	0
systemic	0
injection	0
of	0
pilocarpine	1
in	0
rats	0
.	0

The	0
neuropathology	0
of	0
SNR	0
was	0
investigated	0
using	0
immunohistochemical	0
techniques	0
with	0
the	0
major	0
emphasis	0
on	0
the	0
time	0
-	0
course	0
of	0
changes	0
in	0
neurons	0
and	0
astrocytes	0
.	0

Animals	0
surviving	0
20	0
,	0
30	0
,	0
40	0
,	0
60	0
min	0
,	0
2	0
,	0
3	0
,	0
6	0
hours	0
,	0
1	0
,	0
2	0
,	0
and	0
3	0
days	0
after	0
induction	0
of	0
status	3
epilepticus	4
were	0
perfusion	0
-	0
fixed	0
,	0
and	0
brains	0
processed	0
for	0
immunohistochemical	0
staining	0
of	0
SNR	0
.	0

Nissl	0
-	0
staining	0
and	0
antibodies	0
against	0
the	0
neuron	0
-	0
specific	0
calcium	1
-	0
binding	0
protein	0
,	0
parvalbumin	0
,	0
served	0
to	0
detect	0
neuronal	3
damage	4
in	0
SNR	0
.	0

Antibodies	0
against	0
the	0
astroglia	0
-	0
specific	0
cytoskeletal	0
protein	0
,	0
glial	0
fibrillary	0
acidic	0
protein	0
(	0
GFAP	0
)	0
,	0
and	0
against	0
the	0
glial	0
calcium	1
-	0
binding	0
protein	0
,	0
S	0
-	0
100	0
protein	0
,	0
were	0
used	0
to	0
assess	0
the	0
status	0
of	0
astrocytes	0
.	0

Immunohistochemical	0
staining	0
for	0
serum	0
-	0
albumin	0
and	0
immunoglobulins	0
in	0
brain	0
tissue	0
was	0
taken	0
as	0
indicator	0
of	0
blood	0
-	0
brain	0
barrier	0
disturbances	0
and	0
vasogenic	3
edema	4
formation	0
.	0

Immunohistochemical	0
staining	0
indicated	0
loss	0
of	0
GFAP	0
-	0
staining	0
already	0
at	0
30	0
min	0
after	0
induction	0
of	0
seizures	3
in	0
an	0
oval	0
focus	0
situated	0
in	0
the	0
center	0
of	0
SNR	0
while	0
sparing	0
medial	0
and	0
lateral	0
aspects	0
.	0

At	0
1	0
h	0
there	0
was	0
additional	0
vacuolation	0
in	0
S	0
-	0
100	0
protein	0
staining	0
.	0

By	0
2	0
hours	0
,	0
parvalbumin	0
-	0
staining	0
changed	0
in	0
the	0
central	0
SNR	0
indicating	0
neuronal	3
damage	4
,	0
and	0
Nissl	0
-	0
staining	0
visualized	0
some	0
neuronal	0
distortion	0
.	0

Staining	0
for	0
serum	0
-	0
proteins	0
occurred	0
in	0
a	0
patchy	0
manner	0
throughout	0
the	0
forebrain	0
during	0
the	0
first	0
hours	0
.	0

By	0
6	0
h	0
,	0
vasogenic	3
edema	4
covered	0
the	0
lesioned	3
SNR	4
.	0

By	0
24	0
h	0
,	0
glial	0
and	0
neuronal	0
markers	0
indicated	0
a	0
massive	0
lesion	0
in	0
the	0
center	0
of	0
SNR	0
.	0

By	0
48	0
-	0
72	0
h	0
,	0
astrocytes	0
surrounding	0
the	0
lesion	0
increased	0
in	0
size	0
,	0
and	0
polymorphic	0
phagocytotic	0
cells	0
invaded	0
the	0
damaged	0
area	0
.	0

In	0
a	0
further	0
group	0
of	0
animals	0
surviving	0
1	0
to	0
5	0
days	0
,	0
conventional	0
paraffin	0
-	0
sections	0
confirmed	0
the	0
neuronal	0
and	0
glial	0
damage	3
of	4
SNR	4
.	0

Additional	0
pathology	0
of	0
similar	0
quality	0
was	0
found	0
in	0
the	0
globus	0
pallidus	0
.	0

Since	0
astrocytes	0
were	0
always	0
damaged	0
in	0
parallel	0
with	0
neurons	0
in	0
SNR	0
it	0
is	0
proposed	0
that	0
the	0
anatomical	0
and	0
functional	0
interrelationship	0
between	0
neurons	0
and	0
astrocytes	0
is	0
particularly	0
tight	0
in	0
SNR	0
.	0

Both	0
cell	0
elements	0
may	0
suffer	0
in	0
common	0
from	0
metabolic	0
disturbance	0
and	0
neurotransmitter	3
dysfunction	4
as	0
occur	0
during	0
massive	0
status	3
epilepticus	4
.	0

Neuroprotective	0
effects	0
of	0
melatonin	1
upon	0
the	0
offspring	0
cerebellar	0
cortex	0
in	0
the	0
rat	0
model	0
of	0
BCNU	1
-	0
induced	0
cortical	3
dysplasia	4
.	0

Cortical	3
dysplasia	4
is	0
a	0
malformation	0
characterized	0
by	0
defects	0
in	0
proliferation	0
,	0
migration	0
and	0
maturation	0
.	0

This	0
study	0
was	0
designed	0
to	0
evaluate	0
the	0
alterations	0
in	0
offspring	0
rat	0
cerebellum	0
induced	0
by	0
maternal	0
exposure	0
to	0
carmustine	1
-	0
[	0
1	1
,	2
3	2
-	2
bis	2
(	2
2	2
-	2
chloroethyl	2
)	2
-	2
1	2
-	2
nitrosoure	2
]	0
(	0
BCNU	1
)	0
and	0
to	0
investigate	0
the	0
effects	0
of	0
exogenous	0
melatonin	1
upon	0
cerebellar	0
BCNU	1
-	0
induced	0
cortical	3
dysplasia	4
,	0
using	0
histological	0
and	0
biochemical	0
analyses	0
.	0

Pregnant	0
Wistar	0
rats	0
were	0
assigned	0
to	0
five	0
groups	0
:	0
intact	0
-	0
control	0
,	0
saline	0
-	0
control	0
,	0
melatonin	1
-	0
treated	0
,	0
BCNU	1
-	0
exposed	0
and	0
BCNU	1
-	0
exposed	0
plus	0
melatonin	1
.	0

Rats	0
were	0
exposed	0
to	0
BCNU	1
on	0
embryonic	0
day	0
15	0
and	0
melatonin	1
was	0
given	0
until	0
delivery	0
.	0

Immuno	0
/	0
histochemistry	0
and	0
electron	0
microscopy	0
were	0
carried	0
out	0
on	0
the	0
offspring	0
cerebellum	0
,	0
and	0
levels	0
of	0
malondialdehyde	1
and	0
superoxide	1
dismutase	0
were	0
determined	0
.	0

Histopathologically	0
,	0
typical	0
findings	0
were	0
observed	0
in	0
the	0
cerebella	0
from	0
the	0
control	0
groups	0
,	0
but	0
the	0
findings	0
consistent	0
with	0
early	0
embryonic	0
development	0
were	0
noted	0
in	0
BCNU	1
-	0
exposed	0
cortical	3
dysplasia	4
group	0
.	0

There	0
was	0
a	0
marked	0
increase	0
in	0
the	0
number	0
of	0
TUNEL	0
positive	0
cells	0
and	0
nestin	0
positive	0
cells	0
in	0
BCNU	1
-	0
exposed	0
group	0
,	0
but	0
a	0
decreased	0
immunoreactivity	0
to	0
glial	0
fibrillary	0
acidic	0
protein	0
,	0
synaptophysin	0
and	0
transforming	0
growth	0
factor	0
beta1	0
was	0
observed	0
,	0
indicating	0
a	0
delayed	0
maturation	0
,	0
and	0
melatonin	1
significantly	0
reversed	0
these	0
changes	0
.	0

Malondialdehyde	1
level	0
in	0
BCNU	1
-	0
exposed	0
group	0
was	0
higher	0
than	0
those	0
in	0
control	0
groups	0
and	0
melatonin	1
decreased	0
malondialdehyde	1
levels	0
in	0
BCNU	1
group	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
,	0
while	0
there	0
were	0
no	0
significant	0
differences	0
in	0
the	0
superoxide	1
dismutase	0
levels	0
between	0
these	0
groups	0
.	0

These	0
data	0
suggest	0
that	0
exposure	0
of	0
animals	0
to	0
BCNU	1
during	0
pregnancy	0
leads	0
to	0
delayed	0
maturation	0
of	0
offspring	0
cerebellum	0
and	0
melatonin	1
protects	0
the	0
cerebellum	0
against	0
the	0
effects	0
of	0
BCNU	1
.	0

Reduced	0
cardiotoxicity	3
of	0
doxorubicin	1
given	0
in	0
the	0
form	0
of	0
N	1
-	2
(	2
2	2
-	2
hydroxypropyl	2
)	2
methacrylamide	2
conjugates	0
:	0
and	0
experimental	0
study	0
in	0
the	0
rat	0
.	0

A	0
rat	0
model	0
was	0
used	0
to	0
evaluate	0
the	0
general	0
acute	0
toxicity	3
and	0
the	0
late	0
cardiotoxicity	3
of	0
4	0
mg	0
/	0
kg	0
doxorubicin	1
(	0
D0X	1
)	0
given	0
either	0
as	0
free	0
drug	0
or	0
in	0
the	0
form	0
of	0
three	0
N	1
-	2
(	2
2	2
-	2
hydroxypropyl	2
)	2
methacrylamide	2
(	0
HPMA	1
)	0
copolymer	0
conjugates	0
.	0

In	0
these	0
HPMA	1
copolymers	0
,	0
D0X	1
was	0
covalently	0
bound	0
via	0
peptide	0
linkages	0
that	0
were	0
either	0
non	0
-	0
biodegradable	0
(	0
Gly	0
-	0
Gly	0
)	0
or	0
degradable	0
by	0
lysosomal	0
proteinases	0
(	0
Gly	1
-	2
Phe	2
-	2
Leu	2
-	2
Gly	2
)	0
.	0

In	0
addition	0
,	0
one	0
biodegradable	0
conjugate	0
containing	0
galactosamine	1
was	0
used	0
;	0
this	0
residue	0
was	0
targeted	0
to	0
the	0
liver	0
.	0

0ver	0
the	0
first	0
3	0
weeks	0
after	0
the	0
i	0
.	0
v	0
.	0
administration	0
of	0
free	0
and	0
polymer	0
-	0
bound	0
D0X	1
,	0
all	0
animals	0
showed	0
a	0
transient	0
reduction	0
in	0
body	0
weight	0
.	0

However	0
,	0
the	0
maximal	0
reduction	0
in	0
body	0
weight	0
seen	0
in	0
animals	0
that	0
received	0
polymer	0
-	0
bound	0
D0X	1
(	0
4	0
mg	0
/	0
kg	0
)	0
was	0
significantly	0
lower	0
than	0
that	0
observed	0
in	0
those	0
that	0
received	0
free	0
D0X	1
(	0
4	0
mg	0
/	0
kg	0
)	0
or	0
a	0
mixture	0
of	0
the	0
unmodified	0
parent	0
HPMA	1
copolymer	0
and	0
free	0
D0X	1
(	0
4	0
mg	0
/	0
kg	0
;	0
P	0
less	0
than	0
0	0
.	0
01	0
)	0
.	0

Throughout	0
the	0
study	0
(	0
20	0
weeks	0
)	0
,	0
deaths	0
related	0
to	0
cardiotoxicity	3
were	0
observed	0
only	0
in	0
animals	0
that	0
received	0
either	0
free	0
D0X	1
or	0
the	0
mixture	0
of	0
HPMA	1
copolymer	0
and	0
free	0
D0X	1
;	0
in	0
these	0
cases	0
,	0
histological	0
investigations	0
revealed	0
marked	0
changes	0
in	0
the	0
heart	0
that	0
were	0
consistent	0
with	0
D0X	1
-	0
induced	0
cardiotoxicity	3
.	0

Sequential	0
measurements	0
of	0
cardiac	0
output	0
in	0
surviving	0
animals	0
that	0
received	0
either	0
free	0
D0X	1
or	0
the	0
mixture	0
of	0
HPMA	1
copolymer	0
and	0
free	0
D0X	1
showed	0
a	0
reduction	0
of	0
approximately	0
30	0
%	0
in	0
function	0
beginning	0
at	0
the	0
4th	0
week	0
after	0
drug	0
administration	0
.	0

The	0
heart	0
rate	0
in	0
these	0
animals	0
was	0
approximately	0
12	0
%	0
lower	0
than	0
that	0
measured	0
in	0
age	0
-	0
matched	0
control	0
rats	0
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

Animals	0
that	0
were	0
given	0
the	0
HPMA	1
copolymer	0
conjugates	0
containing	0
D0X	1
exhibited	0
no	0
significant	0
change	0
in	0
cardiac	0
output	0
throughout	0
the	0
study	0
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

In	0
addition	0
,	0
no	0
significant	0
histological	0
change	0
was	0
observed	0
in	0
the	0
heart	0
of	0
animals	0
that	0
received	0
D0X	1
in	0
the	0
form	0
of	0
HPMA	1
copolymer	0
conjugates	0
and	0
were	0
killed	0
at	0
the	0
end	0
of	0
the	0
study	0
.	0

However	0
,	0
these	0
animals	0
had	0
shown	0
a	0
significant	0
increase	0
in	0
heart	0
rate	0
beginning	0
at	0
8	0
weeks	0
after	0
drug	0
administration	0
(	0
P	0
less	0
than	0
0	0
.	0
01	0
)	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
400	0
W0RDS	0
)	0

Corneal	3
ulcers	4
associated	0
with	0
aerosolized	0
crack	1
cocaine	2
use	0
.	0

PURP0SE	0
:	0
We	0
report	0
4	0
cases	0
of	0
corneal	3
ulcers	4
associated	0
with	0
drug	3
abuse	4
.	0

The	0
pathogenesis	0
of	0
these	0
ulcers	3
and	0
management	0
of	0
these	0
patients	0
are	0
also	0
reviewed	0
.	0

METH0DS	0
:	0
Review	0
of	0
all	0
cases	0
of	0
corneal	3
ulcers	4
associated	0
with	0
drug	3
abuse	4
seen	0
at	0
our	0
institution	0
from	0
July	0
2006	0
to	0
December	0
2006	0
.	0

RESULTS	0
:	0
Four	0
patients	0
with	0
corneal	3
ulcers	4
associated	0
with	0
crack	1
cocaine	2
use	0
were	0
reviewed	0
.	0

All	0
corneal	3
ulcers	4
were	0
cultured	0
,	0
and	0
the	0
patients	0
were	0
admitted	0
to	0
the	0
hospital	0
for	0
intensive	0
topical	0
antibiotic	0
treatment	0
.	0

Each	0
patient	0
received	0
comprehensive	0
health	0
care	0
,	0
including	0
medical	0
and	0
substance	3
abuse	4
consultations	0
.	0

Streptococcal	0
organisms	0
were	0
found	0
in	0
3	0
cases	0
and	0
Capnocytophaga	0
and	0
Brevibacterium	0
casei	0
in	0
1	0
patient	0
.	0

The	0
infections	3
responded	0
to	0
antibiotic	0
treatment	0
.	0

Two	0
patients	0
needed	0
a	0
lateral	0
tarsorrhaphy	0
for	0
persistent	0
epithelial	3
defects	4
.	0

C0NCLUSI0NS	0
:	0
Aerosolized	0
crack	1
cocaine	2
use	0
can	0
be	0
associated	0
with	0
the	0
development	0
of	0
corneal	3
ulcers	4
.	0

Drug	3
abuse	4
provides	0
additional	0
challenges	0
for	0
management	0
.	0

Not	0
only	0
treatment	0
of	0
their	0
infections	3
but	0
also	0
the	0
overall	0
poor	0
health	0
of	0
the	0
patients	0
and	0
increased	0
risk	0
of	0
noncompliance	0
need	0
to	0
be	0
addressed	0
.	0

Comprehensive	0
care	0
may	0
provide	0
the	0
patient	0
the	0
opportunity	0
to	0
discontinue	0
their	0
substance	3
abuse	4
,	0
improve	0
their	0
overall	0
health	0
,	0
and	0
prevent	0
future	0
corneal	0
complications	0
.	0

Topical	0
0	0
.	0
025	0
%	0
capsaicin	1
in	0
chronic	0
post	3
-	4
herpetic	4
neuralgia	4
:	0
efficacy	0
,	0
predictors	0
of	0
response	0
and	0
long	0
-	0
term	0
course	0
.	0

In	0
order	0
to	0
evaluate	0
the	0
efficacy	0
,	0
time	0
-	0
course	0
of	0
action	0
and	0
predictors	0
of	0
response	0
to	0
topical	0
capsaicin	1
,	0
39	0
patients	0
with	0
chronic	0
post	3
-	4
herpetic	4
neuralgia	4
(	0
PHN	3
)	0
,	0
median	0
duration	0
24	0
months	0
,	0
were	0
treated	0
with	0
0	0
.	0
025	0
%	0
capsaicin	1
cream	0
for	0
8	0
weeks	0
.	0

During	0
therapy	0
the	0
patients	0
rated	0
their	0
pain	3
on	0
a	0
visual	0
analogue	0
scale	0
(	0
VAS	0
)	0
and	0
a	0
verbal	0
outcome	0
scale	0
.	0

A	0
follow	0
-	0
up	0
investigation	0
was	0
performed	0
10	0
-	0
12	0
months	0
after	0
study	0
onset	0
on	0
the	0
patients	0
who	0
had	0
improved	0
.	0

Nineteen	0
patients	0
(	0
48	0
.	0
7	0
%	0
)	0
substantially	0
improved	0
after	0
the	0
8	0
-	0
week	0
trial	0
;	0
5	0
(	0
12	0
.	0
8	0
%	0
)	0
discontinued	0
therapy	0
due	0
to	0
side	0
-	0
effects	0
such	0
as	0
intolerable	0
capsaicin	1
-	0
induced	0
burning	0
sensations	0
(	0
4	0
)	0
or	0
mastitis	3
(	0
1	0
)	0
;	0
15	0
(	0
38	0
.	0
5	0
%	0
)	0
reported	0
no	0
benefit	0
.	0

The	0
decrease	0
in	0
VAS	0
ratings	0
was	0
significant	0
after	0
2	0
weeks	0
of	0
continuous	0
application	0
.	0

0f	0
the	0
responders	0
72	0
.	0
2	0
%	0
were	0
still	0
improved	0
at	0
the	0
follow	0
-	0
up	0
;	0
only	0
one	0
-	0
third	0
of	0
them	0
had	0
continued	0
application	0
irregularly	0
.	0

Treatment	0
effect	0
was	0
not	0
dependent	0
on	0
patient	0
'	0
s	0
age	0
,	0
duration	0
or	0
localization	0
of	0
PHN	3
(	0
trigeminal	0
involvement	0
was	0
excluded	0
)	0
,	0
sensory	3
disturbance	4
or	0
pain	3
character	0
.	0

Treatment	0
response	0
was	0
not	0
correlated	0
with	0
the	0
incidence	0
,	0
time	0
-	0
course	0
or	0
severity	0
of	0
capsaicin	1
-	0
induced	0
burning	0
.	0

If	0
confirmed	0
in	0
controlled	0
trials	0
,	0
the	0
long	0
-	0
term	0
results	0
of	0
this	0
open	0
,	0
non	0
-	0
randomized	0
study	0
might	0
indicate	0
that	0
the	0
analgesic	0
effect	0
of	0
capsaicin	1
in	0
PHN	3
is	0
mediated	0
by	0
both	0
interference	0
with	0
neuropeptide	0
metabolism	0
and	0
morphological	0
changes	0
(	0
perhaps	0
degeneration	0
)	0
of	0
nociceptive	0
afferents	0
.	0

Myo	1
-	2
inositol	2
-	2
1	2
-	2
phosphate	2
(	0
MIP	1
)	0
synthase	0
inhibition	0
:	0
in	0
-	0
vivo	0
study	0
in	0
rats	0
.	0

Lithium	1
and	0
valproate	1
are	0
the	0
prototypic	0
mood	0
stabilizers	0
and	0
have	0
diverse	0
structures	0
and	0
targets	0
.	0

Both	0
drugs	0
influence	0
inositol	1
metabolism	0
.	0

Lithium	1
inhibits	0
IMPase	0
and	0
valproate	1
inhibits	0
MIP	1
synthase	0
.	0

This	0
study	0
shows	0
that	0
MIP	1
synthase	0
inhibition	0
does	0
not	0
replicate	0
or	0
augment	0
the	0
effects	0
of	0
lithium	1
in	0
the	0
inositol	1
sensitive	0
pilocarpine	1
-	0
induced	0
seizures	3
model	0
.	0

This	0
lack	0
of	0
effects	0
may	0
stem	0
from	0
the	0
low	0
contribution	0
of	0
de	0
-	0
novo	0
synthesis	0
to	0
cellular	0
inositol	1
supply	0
or	0
to	0
the	0
inhibition	0
of	0
the	0
de	0
-	0
novo	0
synthesis	0
by	0
lithium	1
itself	0
.	0

Non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
drugs	0
-	0
associated	0
acute	0
interstitial	3
nephritis	4
with	0
granular	0
tubular	0
basement	0
membrane	0
deposits	0
.	0

Acute	3
tubulo	4
-	4
interstitial	4
nephritis	4
(	0
ATIN	3
)	0
is	0
an	0
important	0
cause	0
of	0
acute	3
renal	4
failure	4
resulting	0
from	0
a	0
variety	0
of	0
insults	0
,	0
including	0
immune	0
complex	0
-	0
mediated	0
tubulo	3
-	4
interstitial	4
injury	4
,	0
but	0
drugs	0
such	0
as	0
non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
drugs	0
(	0
NSAIDs	0
)	0
are	0
a	0
far	0
more	0
frequent	0
cause	0
.	0

0verall	0
,	0
as	0
an	0
entity	0
,	0
ATIN	3
remains	0
under	0
-	0
diagnosed	0
,	0
as	0
symptoms	0
resolve	0
spontaneously	0
if	0
the	0
medication	0
is	0
stopped	0
.	0

We	0
report	0
on	0
a	0
14	0
-	0
year	0
-	0
old	0
boy	0
who	0
developed	0
acute	3
renal	4
failure	4
2	0
weeks	0
after	0
aortic	0
valve	0
surgery	0
.	0

He	0
was	0
put	0
on	0
aspirin	1
following	0
surgery	0
and	0
took	0
ibuprofen	1
for	0
fever	3
for	0
nearly	0
a	0
week	0
prior	0
to	0
presentation	0
.	0

He	0
then	0
presented	0
to	0
the	0
emergency	0
department	0
feeling	0
quite	0
ill	0
and	0
was	0
found	0
to	0
have	0
a	0
blood	1
urea	2
nitrogen	2
(	0
BUN	1
)	0
concentration	0
of	0
of	0
147	0
mg	0
/	0
dl	0
,	0
creatinine	1
of	0
15	0
.	0
3	0
mg	0
/	0
dl	0
and	0
serum	0
potassium	1
of	0
8	0
.	0
7	0
mEq	0
/	0
l	0
.	0

Dialysis	0
was	0
immediately	0
initiated	0
.	0

A	0
kidney	0
biopsy	0
showed	0
inflammatory	0
infiltrate	0
consistent	0
with	0
ATIN	3
.	0

However	0
,	0
in	0
the	0
tubular	0
basement	0
membrane	0
(	0
TBM	0
)	0
,	0
very	0
intense	0
granular	0
deposits	0
of	0
polyclonal	0
IgG	0
and	0
C3	0
were	0
noted	0
.	0

He	0
needed	0
dialysis	0
for	0
2	0
weeks	0
and	0
was	0
treated	0
successfully	0
with	0
steroids	1
for	0
6	0
months	0
.	0

His	0
renal	0
recovery	0
and	0
disappearance	0
of	0
proteinuria	3
took	0
a	0
year	0
.	0

In	0
conclusion	0
,	0
this	0
is	0
a	0
first	0
report	0
of	0
NSAIDs	0
-	0
associated	0
ATIN	3
,	0
showing	0
deposits	0
of	0
granular	0
immune	0
complex	0
present	0
only	0
in	0
the	0
TBM	0
and	0
not	0
in	0
the	0
glomeruli	0
.	0

Rifampicin	1
-	0
associated	0
segmental	0
necrotizing	0
glomerulonephritis	3
in	0
staphylococcal	3
endocarditis	4
.	0

Segmental	0
necrotising	0
glomerulonephritis	3
has	0
been	0
reported	0
as	0
complication	0
of	0
rifampicin	1
therapy	0
in	0
patients	0
receiving	0
treatment	0
for	0
tuberculosis	3
.	0

Changing	0
epidemiology	0
of	0
infections	3
such	0
as	0
infective	3
endocarditis	4
(	0
IE	3
)	0
has	0
led	0
to	0
an	0
increase	0
in	0
the	0
use	0
of	0
rifampicin	1
for	0
Staphylococcal	3
infections	4
.	0

We	0
describe	0
a	0
case	0
of	0
a	0
patient	0
with	0
Staphylococcal	3
IE	4
who	0
developed	0
acute	3
renal	4
failure	4
secondary	0
to	0
a	0
segmental	0
necrotising	0
glomerulonephritis	3
while	0
being	0
treated	0
with	0
rifampicin	1
,	0
and	0
review	0
the	0
literature	0
regarding	0
this	0
complication	0
of	0
rifampicin	1
therapy	0
.	0

Rate	0
of	0
YMDD	0
motif	0
mutants	0
in	0
lamivudine	1
-	0
untreated	0
Iranian	0
patients	0
with	0
chronic	3
hepatitis	4
B	4
virus	4
infection	4
.	0

BACKGR0UND	0
:	0
Lamivudine	1
is	0
used	0
for	0
the	0
treatment	0
of	0
chronic	3
hepatitis	4
B	4
patients	0
.	0

Recent	0
studies	0
show	0
that	0
the	0
YMDD	0
motif	0
mutants	0
(	0
resistant	0
hepatitis	3
B	4
virus	0
)	0
occur	0
as	0
natural	0
genome	0
variability	0
in	0
lamivudine	1
-	0
untreated	0
chronic	3
hepatitis	4
B	4
patients	0
.	0

In	0
this	0
study	0
we	0
aimed	0
to	0
determine	0
the	0
rate	0
of	0
YMDD	0
motif	0
mutants	0
in	0
lamivudine	1
-	0
untreated	0
chronic	3
hepatitis	4
B	4
patients	0
in	0
Iran	0
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
A	0
total	0
of	0
77	0
chronic	3
hepatitis	4
B	4
patients	0
who	0
had	0
not	0
been	0
treated	0
with	0
lamivudine	1
were	0
included	0
in	0
the	0
study	0
.	0

Serum	0
samples	0
from	0
patients	0
were	0
tested	0
by	0
polymerase	0
chain	0
reaction	0
-	0
restriction	0
fragment	0
length	0
polymorphism	0
(	0
PCR	0
-	0
RFLP	0
)	0
for	0
detection	0
of	0
YMDD	0
motif	0
mutants	0
.	0

All	0
patients	0
were	0
also	0
tested	0
for	0
liver	0
enzymes	0
,	0
anti	0
-	0
HCV	0
,	0
HBeAg	1
,	0
and	0
anti	0
-	0
HBe	0
.	0

RESULTS	0
:	0
0f	0
the	0
77	0
patients	0
enrolled	0
in	0
the	0
study	0
,	0
73	0
%	0
were	0
male	0
and	0
27	0
%	0
were	0
female	0
.	0

Mean	0
ALT	0
and	0
AST	0
levels	0
were	0
124	0
.	0
4	0
+	0
/	0
-	0
73	0
.	0
4	0
and	0
103	0
.	0
1	0
+	0
/	0
-	0
81	0
IU	0
/	0
l	0
,	0
respectively	0
.	0

HBeAg	1
was	0
positive	0
in	0
40	0
%	0
and	0
anti	0
-	0
HBe	0
in	0
60	0
%	0
of	0
the	0
patients	0
.	0

Anti	0
-	0
HCV	0
was	0
negative	0
in	0
all	0
of	0
them	0
.	0

YMDD	0
motif	0
mutants	0
were	0
not	0
detected	0
in	0
any	0
of	0
the	0
patients	0
despite	0
the	0
liver	0
enzyme	0
levels	0
and	0
the	0
presence	0
of	0
HBeAg	1
or	0
anti	0
-	0
HBe	0
.	0

C0NCLUSI0N	0
:	0
Although	0
the	0
natural	0
occurrence	0
of	0
YMDD	0
motif	0
mutants	0
in	0
lamivudine	1
-	0
untreated	0
patients	0
with	0
chronic	3
hepatitis	4
B	4
has	0
been	0
reported	0
,	0
these	0
mutants	0
were	0
not	0
detected	0
in	0
Iranian	0
lamivudine	1
-	0
untreated	0
chronic	3
hepatitis	4
B	4
patients	0
.	0

Branch	0
retinal	3
vein	4
occlusion	4
and	0
fluoxetine	1
.	0

A	0
case	0
of	0
branch	0
retinal	3
vein	4
occlusion	4
associated	0
with	0
fluoxetine	1
-	0
induced	0
secondary	0
hypertension	3
is	0
described	0
.	0

Although	0
an	0
infrequent	0
complication	0
of	0
selective	0
serotonin	1
reuptake	0
inhibitor	0
therapy	0
,	0
it	0
is	0
important	0
that	0
ophthalmologists	0
are	0
aware	0
that	0
these	0
agents	0
can	0
cause	0
hypertension	3
because	0
this	0
class	0
of	0
drugs	0
is	0
widely	0
prescribed	0
.	0

The	0
differential	0
effects	0
of	0
bupivacaine	1
and	0
lidocaine	1
on	0
prostaglandin	1
E2	2
release	0
,	0
cyclooxygenase	0
gene	0
expression	0
and	0
pain	3
in	0
a	0
clinical	0
pain	3
model	0
.	0

BACKGR0UND	0
:	0
In	0
addition	0
to	0
blocking	0
nociceptive	0
input	0
from	0
surgical	0
sites	0
,	0
long	0
-	0
acting	0
local	0
anesthetics	0
might	0
directly	0
modulate	0
inflammation	3
.	0

In	0
the	0
present	0
study	0
,	0
we	0
describe	0
the	0
proinflammatory	0
effects	0
of	0
bupivacaine	1
on	0
local	0
prostaglandin	1
E2	2
(	0
PGE2	1
)	0
production	0
and	0
cyclooxygenase	0
(	0
C0X	0
)	0
gene	0
expression	0
that	0
increases	0
postoperative	3
pain	4
in	0
human	0
subjects	0
.	0

METH0DS	0
:	0
Subjects	0
(	0
n	0
=	0
114	0
)	0
undergoing	0
extraction	0
of	0
impacted	0
third	0
molars	0
received	0
either	0
2	0
%	0
lidocaine	1
or	0
0	0
.	0
5	0
%	0
bupivacaine	1
before	0
surgery	0
and	0
either	0
rofecoxib	1
50	0
mg	0
or	0
placebo	0
orally	0
90	0
min	0
before	0
surgery	0
and	0
for	0
the	0
following	0
48	0
h	0
.	0

0ral	0
mucosal	0
biopsies	0
were	0
taken	0
before	0
surgery	0
and	0
48	0
h	0
after	0
surgery	0
.	0

After	0
extraction	0
,	0
a	0
microdialysis	0
probe	0
was	0
placed	0
at	0
the	0
surgical	0
site	0
for	0
PGE2	1
and	0
thromboxane	1
B2	2
(	0
TXB2	1
)	0
measurements	0
.	0

RESULTS	0
:	0
The	0
bupivacaine	1
/	0
rofecoxib	1
group	0
reported	0
significantly	0
less	0
pain	3
,	0
as	0
assessed	0
by	0
a	0
visual	0
analog	0
scale	0
,	0
compared	0
with	0
the	0
other	0
three	0
treatment	0
groups	0
over	0
the	0
first	0
4	0
h	0
.	0

However	0
,	0
the	0
bupivacaine	1
/	0
placebo	0
group	0
reported	0
significantly	0
more	0
pain	3
at	0
24	0
h	0
and	0
PGE2	1
levels	0
during	0
the	0
first	0
4	0
h	0
were	0
significantly	0
higher	0
than	0
the	0
other	0
three	0
treatment	0
groups	0
.	0

Moreover	0
,	0
bupivacaine	1
significantly	0
increased	0
C0X	0
-	0
2	0
gene	0
expression	0
at	0
48	0
h	0
as	0
compared	0
with	0
the	0
lidocaine	1
/	0
placebo	0
group	0
.	0

Thromboxane	1
levels	0
were	0
not	0
significantly	0
affected	0
by	0
any	0
of	0
the	0
treatments	0
,	0
indicating	0
that	0
the	0
effects	0
seen	0
were	0
attributable	0
to	0
inhibition	0
of	0
C0X	0
-	0
2	0
,	0
but	0
not	0
C0X	0
-	0
1	0
.	0

C0NCLUSI0NS	0
:	0
These	0
results	0
suggest	0
that	0
bupivacaine	1
stimulates	0
C0X	0
-	0
2	0
gene	0
expression	0
after	0
tissue	3
injury	4
,	0
which	0
is	0
associated	0
with	0
higher	0
PGE2	1
production	0
and	0
pain	3
after	0
the	0
local	0
anesthetic	0
effect	0
dissipates	0
.	0

p75NTR	0
expression	0
in	0
rat	0
urinary	0
bladder	0
sensory	0
neurons	0
and	0
spinal	0
cord	0
with	0
cyclophosphamide	1
-	0
induced	0
cystitis	3
.	0

A	0
role	0
for	0
nerve	0
growth	0
factor	0
(	0
NGF	0
)	0
in	0
contributing	0
to	0
increased	0
voiding	0
frequency	0
and	0
altered	0
sensation	0
from	0
the	0
urinary	0
bladder	0
has	0
been	0
suggested	0
.	0

Previous	0
studies	0
have	0
examined	0
the	0
expression	0
and	0
regulation	0
of	0
tyrosine	1
kinase	0
receptors	0
(	0
Trks	0
)	0
in	0
micturition	0
reflexes	0
with	0
urinary	3
bladder	4
inflammation	4
.	0

The	0
present	0
studies	0
examine	0
the	0
expression	0
and	0
regulation	0
of	0
another	0
receptor	0
known	0
to	0
bind	0
NGF	0
,	0
p75	0
(	0
NTR	0
)	0
,	0
after	0
various	0
durations	0
of	0
bladder	3
inflammation	4
induced	0
by	0
cyclophosphamide	1
(	0
CYP	1
)	0
.	0

CYP	1
-	0
induced	0
cystitis	3
increased	0
(	0
P	0
<	0
or	0
=	0
0	0
.	0
001	0
)	0
p75	0
(	0
NTR	0
)	0
expression	0
in	0
the	0
superficial	0
lateral	0
and	0
medial	0
dorsal	0
horn	0
in	0
L1	0
-	0
L2	0
and	0
L6	0
-	0
S1	0
spinal	0
segments	0
.	0

The	0
number	0
of	0
p75	0
(	0
NTR	0
)	0
-	0
immunoreactive	0
(	0
-	0
IR	0
)	0
cells	0
in	0
the	0
lumbosacral	0
dorsal	0
root	0
ganglia	0
(	0
DRG	0
)	0
also	0
increased	0
(	0
P	0
<	0
or	0
=	0
0	0
.	0
05	0
)	0
with	0
CYP	1
-	0
induced	0
cystitis	3
(	0
acute	0
,	0
intermediate	0
,	0
and	0
chronic	0
)	0
.	0

Quantitative	0
,	0
real	0
-	0
time	0
polymerase	0
chain	0
reaction	0
also	0
demonstrated	0
significant	0
increases	0
(	0
P	0
<	0
or	0
=	0
0	0
.	0
01	0
)	0
in	0
p75	0
(	0
NTR	0
)	0
mRNA	0
in	0
DRG	0
with	0
intermediate	0
and	0
chronic	0
CYP	1
-	0
induced	0
cystitis	3
.	0

Retrograde	0
dye	0
-	0
tracing	0
techniques	0
with	0
Fastblue	0
were	0
used	0
to	0
identify	0
presumptive	0
bladder	0
afferent	0
cells	0
in	0
the	0
lumbosacral	0
DRG	0
.	0

In	0
bladder	0
afferent	0
cells	0
in	0
DRG	0
,	0
p75	0
(	0
NTR	0
)	0
-	0
IR	0
was	0
also	0
increased	0
(	0
P	0
<	0
or	0
=	0
0	0
.	0
01	0
)	0
with	0
cystitis	3
.	0

In	0
addition	0
to	0
increases	0
in	0
p75	0
(	0
NTR	0
)	0
-	0
IR	0
in	0
DRG	0
cell	0
bodies	0
,	0
increases	0
(	0
P	0
<	0
or	0
=	0
0	0
.	0
001	0
)	0
in	0
pericellular	0
(	0
encircling	0
DRG	0
cells	0
)	0
p75	0
(	0
NTR	0
)	0
-	0
IR	0
in	0
DRG	0
also	0
increased	0
.	0

Confocal	0
analyses	0
demonstrated	0
that	0
pericellular	0
p75	0
(	0
NTR	0
)	0
-	0
IR	0
was	0
not	0
colocalized	0
with	0
the	0
glial	0
marker	0
,	0
glial	0
fibrillary	0
acidic	0
protein	0
(	0
GFAP	0
)	0
.	0

These	0
studies	0
demonstrate	0
that	0
p75	0
(	0
NTR	0
)	0
expression	0
in	0
micturition	0
reflexes	0
is	0
present	0
constitutively	0
and	0
modified	0
by	0
bladder	3
inflammation	4
.	0

The	0
functional	0
significance	0
of	0
p75	0
(	0
NTR	0
)	0
expression	0
in	0
micturition	0
reflexes	0
remains	0
to	0
be	0
determined	0
.	0

Azathioprine	1
-	0
induced	0
suicidal	0
erythrocyte	0
death	0
.	0

BACKGR0UND	0
:	0
Azathioprine	1
is	0
widely	0
used	0
as	0
an	0
immunosuppressive	0
drug	0
.	0

The	0
side	0
effects	0
of	0
azathioprine	1
include	0
anemia	3
,	0
which	0
has	0
been	0
attributed	0
to	0
bone	0
marrow	0
suppression	0
.	0

Alternatively	0
,	0
anemia	3
could	0
result	0
from	0
accelerated	0
suicidal	0
erythrocyte	0
death	0
or	0
eryptosis	0
,	0
which	0
is	0
characterized	0
by	0
exposure	0
of	0
phosphatidylserine	1
(	0
PS	1
)	0
at	0
the	0
erythrocyte	0
surface	0
and	0
by	0
cell	0
shrinkage	0
.	0

METH0DS	0
:	0
The	0
present	0
experiments	0
explored	0
whether	0
azathioprine	1
influences	0
eryptosis	0
.	0

According	0
to	0
annexin	0
V	0
binding	0
,	0
erythrocytes	0
from	0
patients	0
indeed	0
showed	0
a	0
significant	0
increase	0
of	0
PS	1
exposure	0
within	0
1	0
week	0
of	0
treatment	0
with	0
azathioprine	1
.	0

In	0
a	0
second	0
series	0
,	0
cytosolic	0
Ca2	1
+	0
activity	0
(	0
Fluo3	1
fluorescence	0
)	0
,	0
cell	0
volume	0
(	0
forward	0
scatter	0
)	0
,	0
and	0
PS	1
-	0
exposure	0
(	0
annexin	0
V	0
binding	0
)	0
were	0
determined	0
by	0
FACS	0
analysis	0
in	0
erythrocytes	0
from	0
healthy	0
volunteers	0
.	0

RESULTS	0
:	0
Exposure	0
to	0
azathioprine	1
(	0
>	0
or	0
=	0
2	0
microg	0
/	0
mL	0
)	0
for	0
48	0
hours	0
increased	0
cytosolic	0
Ca2	1
+	0
activity	0
and	0
annexin	0
V	0
binding	0
and	0
decreased	0
forward	0
scatter	0
.	0

The	0
effect	0
of	0
azathioprine	1
on	0
both	0
annexin	0
V	0
binding	0
and	0
forward	0
scatter	0
was	0
significantly	0
blunted	0
in	0
the	0
nominal	0
absence	0
of	0
extracellular	0
Ca2	1
+	0
.	0

C0NCLUSI0NS	0
:	0
Azathioprine	1
triggers	0
suicidal	0
erythrocyte	0
death	0
,	0
an	0
effect	0
presumably	0
contributing	0
to	0
azathioprine	1
-	0
induced	0
anemia	3
.	0

Levetiracetam	1
as	0
an	0
adjunct	0
to	0
phenobarbital	1
treatment	0
in	0
cats	0
with	0
suspected	0
idiopathic	3
epilepsy	4
.	0

0BJECTIVE	0
:	0
To	0
assess	0
pharmacokinetics	0
,	0
efficacy	0
,	0
and	0
tolerability	0
of	0
oral	0
levetiracetam	1
administered	0
as	0
an	0
adjunct	0
to	0
phenobarbital	1
treatment	0
in	0
cats	0
with	0
poorly	0
controlled	0
suspected	0
idiopathic	3
epilepsy	4
.	0

DESIGN	0
-	0
0pen	0
-	0
label	0
,	0
noncomparative	0
clinical	0
trial	0
.	0

ANIMALS	0
:	0
12	0
cats	0
suspected	0
to	0
have	0
idiopathic	3
epilepsy	4
that	0
was	0
poorly	0
controlled	0
with	0
phenobarbital	1
or	0
that	0
had	0
unacceptable	0
adverse	0
effects	0
when	0
treated	0
with	0
phenobarbital	1
.	0

PR0CEDURES	0
:	0
Cats	0
were	0
treated	0
with	0
levetiracetam	1
(	0
20	0
mg	0
/	0
kg	0
[	0
9	0
.	0
1	0
mg	0
/	0
lb	0
]	0
,	0
P0	0
,	0
q	0
8	0
h	0
)	0
.	0

After	0
a	0
minimum	0
of	0
1	0
week	0
of	0
treatment	0
,	0
serum	0
levetiracetam	1
concentrations	0
were	0
measured	0
before	0
and	0
2	0
,	0
4	0
,	0
and	0
6	0
hours	0
after	0
drug	0
administration	0
,	0
and	0
maximum	0
and	0
minimum	0
serum	0
concentrations	0
and	0
elimination	0
half	0
-	0
life	0
were	0
calculated	0
.	0

Seizure	3
frequencies	0
before	0
and	0
after	0
initiation	0
of	0
levetiracetam	1
treatment	0
were	0
compared	0
,	0
and	0
adverse	0
effects	0
were	0
recorded	0
.	0

RESULTS	0
:	0
Median	0
maximum	0
serum	0
levetiracetam	1
concentration	0
was	0
25	0
.	0
5	0
microg	0
/	0
mL	0
,	0
median	0
minimum	0
serum	0
levetiracetam	1
concentration	0
was	0
8	0
.	0
3	0
microg	0
/	0
mL	0
,	0
and	0
median	0
elimination	0
half	0
-	0
life	0
was	0
2	0
.	0
9	0
hours	0
.	0

Median	0
seizure	3
frequency	0
prior	0
to	0
treatment	0
with	0
levetiracetam	1
(	0
2	0
.	0
1	0
seizures	3
/	0
mo	0
)	0
was	0
significantly	0
higher	0
than	0
median	0
seizure	3
frequency	0
after	0
initiation	0
of	0
levetiracetam	1
treatment	0
(	0
0	0
.	0
42	0
seizures	3
/	0
mo	0
)	0
,	0
and	0
7	0
of	0
10	0
cats	0
were	0
classified	0
as	0
having	0
responded	0
to	0
levetiracetam	1
treatment	0
(	0
ie	0
,	0
reduction	0
in	0
seizure	3
frequency	0
of	0
>	0
or	0
=	0
50	0
%	0
)	0
.	0

Two	0
cats	0
had	0
transient	0
lethargy	3
and	0
inappetence	3
.	0

C0NCLUSI0NS	0
AND	0
CLINICAL	0
RELEVANCE	0
:	0
Results	0
suggested	0
that	0
levetiracetam	1
is	0
well	0
tolerated	0
in	0
cats	0
and	0
may	0
be	0
useful	0
as	0
an	0
adjunct	0
to	0
phenobarbital	1
treatment	0
in	0
cats	0
with	0
idiopathic	3
epilepsy	4
.	0

Serotonin	1
reuptake	0
inhibitors	0
,	0
paranoia	3
,	0
and	0
the	0
ventral	0
basal	0
ganglia	0
.	0

Antidepressants	0
have	0
previously	0
been	0
associated	0
with	0
paranoid	3
reactions	0
in	0
psychiatric	0
patients	0
.	0

Five	0
cases	0
of	0
paranoid	3
exacerbation	0
with	0
the	0
serotonin	1
reuptake	0
inhibitors	0
fluoxetine	1
and	0
amitriptyline	1
are	0
reported	0
here	0
.	0

Elements	0
common	0
to	0
these	0
cases	0
included	0
a	0
history	0
of	0
paranoid	3
symptomatology	0
and	0
the	0
concomitant	0
occurrence	0
of	0
depressive	3
and	4
psychotic	4
symptoms	4
.	0

Complicated	0
depressive	3
disorders	4
(	0
including	0
atypicality	0
of	0
course	0
and	0
symptomatology	0
,	0
chronicity	0
,	0
psychosis	3
,	0
bipolarity	0
,	0
and	0
secondary	0
onset	0
in	0
the	0
course	0
of	0
a	0
primary	0
psychosis	3
)	0
may	0
present	0
particular	0
vulnerability	0
to	0
paranoid	3
exacerbations	0
associated	0
with	0
serotonin	1
reuptake	0
inhibitors	0
.	0

Although	0
the	0
pharmacology	0
and	0
neurobiology	0
of	0
paranoia	3
remain	0
cryptic	0
,	0
several	0
mechanisms	0
,	0
including	0
5HT3	0
receptor	0
-	0
mediated	0
dopamine	1
release	0
,	0
beta	0
-	0
noradrenergic	0
receptor	0
downregulation	0
,	0
or	0
GABAB	0
receptor	0
upregulation	0
acting	0
in	0
the	0
vicinity	0
of	0
the	0
ventral	0
basal	0
ganglia	0
(	0
possibly	0
in	0
lateral	0
orbitofrontal	0
or	0
anterior	0
cingulate	0
circuits	0
)	0
,	0
might	0
apply	0
to	0
this	0
phenomenon	0
.	0

These	0
cases	0
call	0
attention	0
to	0
possible	0
paranoid	3
exacerbations	0
with	0
serotonin	1
reuptake	0
blockers	0
in	0
select	0
patients	0
and	0
raise	0
neurobiological	0
considerations	0
regarding	0
paranoia	3
.	0

Clinical	0
comparison	0
of	0
cardiorespiratory	0
effects	0
during	0
unilateral	0
and	0
conventional	0
spinal	0
anaesthesia	0
.	0

BACKGR0UND	0
:	0
Spinal	0
anaesthesia	0
is	0
widely	0
employed	0
in	0
clinical	0
practice	0
but	0
has	0
the	0
main	0
drawback	0
of	0
post	0
-	0
spinal	0
block	0
hypotension	3
.	0

Efforts	0
must	0
therefore	0
continue	0
to	0
be	0
made	0
to	0
obviate	0
this	0
setback	0
0BJECTIVE	0
:	0
To	0
evaluate	0
the	0
cardiovascular	0
and	0
respiratory	0
changes	0
during	0
unilateral	0
and	0
conventional	0
spinal	0
anaesthesia	0
.	0

METH0DS	0
:	0
With	0
ethical	0
approval	0
,	0
we	0
studied	0
74	0
American	0
Society	0
of	0
Anesthesiologists	0
(	0
ASA	0
)	0
,	0
physical	0
status	0
class	0
1	0
and	0
2	0
patients	0
scheduled	0
for	0
elective	0
unilateral	0
lower	0
limb	0
surgery	0
.	0

Patients	0
were	0
randomly	0
allocated	0
into	0
one	0
of	0
two	0
groups	0
:	0
lateral	0
and	0
conventional	0
spinal	0
anaesthesia	0
groups	0
.	0

In	0
the	0
lateral	0
position	0
with	0
operative	0
side	0
down	0
,	0
patients	0
recived	0
10	0
mg	0
(	0
2mls	0
)	0
of	0
0	0
.	0
5	0
%	0
hyperbaric	0
bupivacaine	1
through	0
a	0
25	0
-	0
gauge	0
spinal	0
needle	0
.	0

Patients	0
in	0
the	0
unilateral	0
group	0
were	0
maintained	0
in	0
the	0
lateral	0
position	0
for	0
15	0
minutes	0
following	0
spinal	0
injection	0
while	0
those	0
in	0
the	0
conventional	0
group	0
were	0
turned	0
supine	0
immediately	0
after	0
injection	0
.	0

Blood	0
pressure	0
,	0
heart	0
rate	0
,	0
respiratory	0
rate	0
and	0
oxygen	1
saturation	0
were	0
monitored	0
over	0
1	0
hour	0
.	0

RESULTS	0
:	0
Three	0
patients	0
(	0
8	0
.	0
1	0
%	0
)	0
in	0
the	0
unilateral	0
group	0
and	0
5	0
(	0
13	0
.	0
5	0
%	0
)	0
in	0
the	0
conventional	0
group	0
developed	0
hypotension	3
,	0
P	0
=	0
0	0
.	0
71	0
.	0

Four	0
(	0
10	0
.	0
8	0
%	0
)	0
patients	0
in	0
the	0
conventional	0
group	0
and	0
1	0
(	0
2	0
.	0
7	0
%	0
)	0
in	0
the	0
unilateral	0
group	0
,	0
P	0
=	0
0	0
.	0
17	0
required	0
epinephrine	1
infusion	0
to	0
treat	0
hypotension	3
.	0

Patients	0
in	0
the	0
conventional	0
group	0
had	0
statistically	0
significant	0
greater	0
fall	0
in	0
the	0
systolic	0
blood	0
pressures	0
at	0
15	0
,	0
30	0
and	0
45	0
minutes	0
when	0
compared	0
to	0
the	0
baseline	0
(	0
P	0
=	0
0	0
.	0
003	0
,	0
0	0
.	0
001	0
and	0
0	0
.	0
004	0
)	0
.	0

The	0
mean	0
respiratory	0
rate	0
and	0
oxygen	1
saturations	0
in	0
the	0
two	0
groups	0
were	0
similar	0
.	0

C0NCLUSI0N	0
:	0
Compared	0
to	0
conventional	0
spinal	0
anaesthesia	0
,	0
unilateral	0
spinal	0
anaesthesia	0
was	0
associated	0
with	0
fewer	0
cardiovascular	0
perturbations	0
.	0

Also	0
,	0
the	0
type	0
of	0
spinal	0
block	0
instituted	0
affected	0
neither	0
the	0
respiratory	0
rate	0
nor	0
the	0
arterial	0
oxygen	1
saturation	0
.	0

Spectrum	0
of	0
adverse	0
events	0
after	0
generic	0
HAART	0
in	0
southern	0
Indian	0
HIV	3
-	4
infected	4
patients	0
.	0

To	0
determine	0
the	0
incidence	0
of	0
clinically	0
significant	0
adverse	0
events	0
after	0
long	0
-	0
term	0
,	0
fixed	0
-	0
dose	0
,	0
generic	0
highly	0
active	0
antiretroviral	0
therapy	0
(	0
HAART	0
)	0
use	0
among	0
HIV	3
-	4
infected	4
individuals	0
in	0
South	0
India	0
,	0
we	0
examined	0
the	0
experiences	0
of	0
3154	0
HIV	3
-	4
infected	4
individuals	0
who	0
received	0
a	0
minimum	0
of	0
3	0
months	0
of	0
generic	0
HAART	0
between	0
February	0
1996	0
and	0
December	0
2006	0
at	0
a	0
tertiary	0
HIV	0
care	0
referral	0
center	0
in	0
South	0
India	0
.	0

The	0
most	0
common	0
regimens	0
were	0
3TC	1
+	0
d4T	1
+	0
nevirapine	1
(	0
NVP	1
)	0
(	0
54	0
.	0
8	0
%	0
)	0
,	0
zidovudine	1
(	0
AZT	1
)	0
+	0
3TC	1
+	0
NVP	1
(	0
14	0
.	0
5	0
%	0
)	0
,	0
3TC	1
+	0
d4T	1
+	0
efavirenz	1
(	0
EFV	1
)	0
(	0
20	0
.	0
1	0
%	0
)	0
,	0
and	0
AZT	1
+	0
3TC	1
+	0
EFV	1
(	0
5	0
.	0
4	0
%	0
)	0
.	0

The	0
most	0
common	0
adverse	0
events	0
and	0
median	0
CD4	0
at	0
time	0
of	0
event	0
were	0
rash	3
(	0
15	0
.	0
2	0
%	0
;	0
CD4	0
,	0
285	0
cells	0
/	0
microL	0
)	0
and	0
peripheral	3
neuropathy	4
(	0
9	0
.	0
0	0
%	0
and	0
348	0
cells	0
/	0
microL	0
)	0
.	0

Clinically	0
significant	0
anemia	3
(	0
hemoglobin	0
<	0
7	0
g	0
/	0
dL	0
)	0
was	0
observed	0
in	0
5	0
.	0
4	0
%	0
of	0
patients	0
(	0
CD4	0
,	0
165	0
cells	0
/	0
microL	0
)	0
and	0
hepatitis	3
(	0
clinical	0
jaundice	3
with	0
alanine	1
aminotransferase	0
>	0
5	0
times	0
upper	0
limits	0
of	0
normal	0
)	0
in	0
3	0
.	0
5	0
%	0
of	0
patients	0
(	0
CD4	0
,	0
260	0
cells	0
/	0
microL	0
)	0
.	0

Women	0
were	0
significantly	0
more	0
likely	0
to	0
experience	0
lactic	3
acidosis	4
,	0
while	0
men	0
were	0
significantly	0
more	0
likely	0
to	0
experience	0
immune	3
reconstitution	4
syndrome	4
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

Among	0
the	0
patients	0
with	0
1	0
year	0
of	0
follow	0
-	0
up	0
,	0
NVP	1
therapy	0
was	0
significantly	0
associated	0
with	0
developing	0
rash	3
and	0
d4T	1
therapy	0
with	0
developing	0
peripheral	3
neuropathy	4
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

Anemia	3
and	0
hepatitis	3
often	0
occur	0
within	0
12	0
weeks	0
of	0
initiating	0
generic	0
HAART	0
.	0

Frequent	0
and	0
early	0
monitoring	0
for	0
these	0
toxicities	3
is	0
warranted	0
in	0
developing	0
countries	0
where	0
generic	0
HAART	0
is	0
increasingly	0
available	0
.	0

Thalidomide	1
and	0
sensory	3
neurotoxicity	4
:	0
a	0
neurophysiological	0
study	0
.	0

BACKGR0UND	0
:	0
Recent	0
studies	0
confirmed	0
a	0
high	0
incidence	0
of	0
sensory	3
axonal	4
neuropathy	4
in	0
patients	0
treated	0
with	0
different	0
doses	0
of	0
thalidomide	1
.	0

The	0
study	0
'	0
s	0
aims	0
were	0
to	0
measure	0
variations	0
in	0
sural	0
nerve	0
sensory	0
action	0
potential	0
(	0
SAP	0
)	0
amplitude	0
in	0
patients	0
with	0
refractory	0
cutaneous	3
lupus	4
erythematosus	4
(	0
CLE	3
)	0
treated	0
with	0
thalidomide	1
and	0
use	0
these	0
findings	0
to	0
identify	0
the	0
neurotoxic	3
potential	0
of	0
thalidomide	1
and	0
the	0
recovery	0
capacity	0
of	0
sensory	0
fibres	0
after	0
discontinuation	0
of	0
treatment	0
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
Clinical	0
and	0
electrophysiological	0
data	0
in	0
12	0
female	0
patients	0
with	0
CLE	3
during	0
treatment	0
with	0
thalidomide	1
and	0
up	0
to	0
47	0
months	0
after	0
discontinuation	0
of	0
treatment	0
were	0
analysed	0
.	0

Sural	0
nerve	0
SAP	0
amplitude	0
reduction	0
>	0
or	0
=	0
40	0
%	0
was	0
the	0
criteria	0
for	0
discontinuing	0
therapy	0
.	0

RESULTS	0
:	0
During	0
treatment	0
,	0
11	0
patients	0
showed	0
a	0
reduction	0
in	0
sural	0
nerve	0
SAP	0
amplitude	0
compared	0
to	0
baseline	0
values	0
(	0
9	0
with	0
a	0
reduction	0
>	0
or	0
=	0
50	0
%	0
and	0
2	0
<	0
50	0
%	0
)	0
.	0

0ne	0
patient	0
showed	0
no	0
changes	0
in	0
SAP	0
amplitude	0
.	0

Five	0
patients	0
complained	0
of	0
paresthesias	3
and	0
leg	0
cramps	3
.	0

After	0
thalidomide	1
treatment	0
,	0
sural	0
SAP	0
amplitude	0
recovered	0
in	0
3	0
patients	0
.	0

At	0
detection	0
of	0
reduction	0
in	0
sural	0
nerve	0
SAP	0
amplitude	0
,	0
the	0
median	0
thalidomide	1
cumulative	0
dose	0
was	0
21	0
.	0
4	0
g	0
.	0

The	0
threshold	0
neurotoxic	3
dosage	0
is	0
lower	0
than	0
previously	0
reported	0
.	0

C0NCLUSI0NS	0
:	0
Sural	0
nerve	0
SAP	0
amplitude	0
reduction	0
is	0
a	0
reliable	0
and	0
sensitive	0
marker	0
of	0
degeneration	0
and	0
recovery	0
of	0
sensory	0
fibres	0
.	0

This	0
electrophysiological	0
parameter	0
provides	0
information	0
about	0
subclinical	0
neurotoxic	3
potential	0
of	0
thalidomide	1
but	0
is	0
not	0
helpful	0
in	0
predicting	0
the	0
appearance	0
of	0
sensory	0
symptoms	0
.	0

Five	0
cases	0
of	0
encephalitis	3
during	0
treatment	0
of	0
loiasis	3
with	0
diethylcarbamazine	1
.	0

Five	0
cases	0
of	0
encephalitis	3
following	0
treatment	0
with	0
diethylcarbamazine	1
(	0
DEC	1
)	0
were	0
observed	0
in	0
Congolese	0
patients	0
with	0
Loa	0
loa	0
filariasis	3
.	0

Two	0
cases	0
had	0
a	0
fatal	0
outcome	0
and	0
one	0
resulted	0
in	0
severe	0
sequelae	0
.	0

The	0
notable	0
fact	0
was	0
that	0
this	0
complication	0
occurred	0
in	0
three	0
patients	0
hospitalized	0
before	0
treatment	0
began	0
,	0
with	0
whom	0
particularly	0
strict	0
therapeutic	0
precautions	0
were	0
taken	0
,	0
i	0
.	0
e	0
.	0
,	0
initial	0
dose	0
less	0
than	0
10	0
mg	0
of	0
DEC	1
,	0
very	0
gradual	0
dose	0
increases	0
,	0
and	0
associated	0
anti	0
-	0
allergic	0
treatment	0
.	0

This	0
type	0
of	0
drug	0
-	0
induced	0
complication	0
may	0
not	0
be	0
that	0
uncommon	0
in	0
highly	0
endemic	0
regions	0
.	0

It	0
occurs	0
primarily	0
,	0
but	0
not	0
exclusively	0
,	0
in	0
subjects	0
presenting	0
with	0
a	0
high	0
microfilarial	0
load	0
.	0

The	0
relationship	0
between	0
the	0
occurrence	0
of	0
encephalitis	3
and	0
the	0
decrease	0
in	0
microfilaremia	3
is	0
evident	0
.	0

The	0
pathophysiological	0
mechanisms	0
are	0
discussed	0
in	0
the	0
light	0
of	0
these	0
observations	0
and	0
the	0
few	0
other	0
comments	0
on	0
this	0
subject	0
published	0
in	0
the	0
literature	0
.	0

Amiodarone	1
-	0
related	0
pulmonary	3
mass	4
and	0
unique	0
membranous	3
glomerulonephritis	4
in	0
a	0
patient	0
with	0
valvular	3
heart	4
disease	4
:	0
Diagnostic	0
pitfall	0
and	0
new	0
findings	0
.	0

Amiodarone	1
is	0
an	0
anti	0
-	0
arrhythmic	3
drug	0
for	0
life	0
-	0
threatening	0
tachycardia	3
,	0
but	0
various	0
adverse	0
effects	0
have	0
been	0
reported	0
.	0

Reported	0
herein	0
is	0
an	0
autopsy	0
case	0
of	0
valvular	3
heart	4
disease	4
,	0
in	0
a	0
patient	0
who	0
developed	0
a	0
lung	3
mass	4
(	0
1	0
.	0
5	0
cm	0
in	0
diameter	0
)	0
and	0
proteinuria	3
(	0
2	0
.	0
76	0
g	0
/	0
day	0
)	0
after	0
treatment	0
with	0
amiodarone	1
for	0
a	0
long	0
time	0
.	0

The	0
lung	3
mass	4
was	0
highly	0
suspected	0
to	0
be	0
lung	3
cancer	4
on	0
CT	0
and	0
positron	0
emission	0
tomography	0
,	0
but	0
histologically	0
the	0
lesion	0
was	0
composed	0
of	0
lymphoplasmacytic	0
infiltrates	0
in	0
alveolar	0
walls	0
and	0
intra	0
-	0
alveolar	0
accumulation	0
of	0
foamy	0
macrophages	0
containing	0
characteristic	0
myelinoid	0
bodies	0
,	0
indicating	0
that	0
it	0
was	0
an	0
amiodarone	1
-	0
related	0
lesion	0
.	0

In	0
addition	0
,	0
the	0
lung	0
tissue	0
had	0
unevenly	0
distributed	0
hemosiderin	3
deposition	0
,	0
and	0
abnormally	0
tortuous	0
capillaries	0
were	0
seen	0
in	0
the	0
mass	0
and	0
in	0
heavily	0
hemosiderotic	3
lung	0
portions	0
outside	0
the	0
mass	0
.	0

In	0
the	0
kidneys	0
,	0
glomeruli	0
had	0
membrane	0
spikes	0
,	0
prominent	0
swelling	0
of	0
podocytes	0
and	0
subepithelial	0
deposits	0
,	0
which	0
were	0
sometimes	0
large	0
and	0
hump	0
-	0
like	0
.	0

Autoimmune	3
diseases	4
,	0
viral	3
hepatitis	4
,	0
malignant	0
neoplasms	3
or	0
other	0
diseases	0
with	0
a	0
known	0
relationship	0
to	0
membranous	3
glomerulonephritis	4
were	0
not	0
found	0
.	0

The	0
present	0
case	0
highlights	0
the	0
possibility	0
that	0
differential	0
diagnosis	0
between	0
an	0
amiodarone	1
-	0
related	0
pulmonary	3
lesion	4
and	0
a	0
neoplasm	3
can	0
be	0
very	0
difficult	0
radiologically	0
,	0
and	0
suggests	0
that	0
membranous	3
glomerulonephritis	4
might	0
be	0
another	0
possible	0
complication	0
of	0
amiodarone	1
treatment	0
.	0

Risk	0
of	0
coronary	3
artery	4
disease	4
associated	0
with	0
initial	0
sulphonylurea	1
treatment	0
of	0
patients	0
with	0
type	3
2	4
diabetes	4
:	0
a	0
matched	0
case	0
-	0
control	0
study	0
.	0

AIMS	0
:	0
This	0
study	0
sought	0
to	0
assess	0
the	0
risk	0
of	0
developing	0
coronary	3
artery	4
disease	4
(	0
CAD	3
)	0
associated	0
with	0
initial	0
treatment	0
of	0
type	3
2	4
diabetes	4
with	0
different	0
sulphonylureas	1
.	0

METH0DS	0
:	0
In	0
type	3
2	4
diabetic	4
patients	0
,	0
cases	0
who	0
developed	0
CAD	3
were	0
compared	0
retrospectively	0
with	0
controls	0
that	0
did	0
not	0
.	0

The	0
20	0
-	0
year	0
risk	0
of	0
CAD	3
at	0
diagnosis	0
of	0
diabetes	3
,	0
using	0
the	0
UKPDS	0
risk	0
engine	0
,	0
was	0
used	0
to	0
match	0
cases	0
with	0
controls	0
.	0

RESULTS	0
:	0
The	0
76	0
cases	0
of	0
CAD	3
were	0
compared	0
with	0
152	0
controls	0
.	0

The	0
hazard	0
of	0
developing	0
CAD	3
(	0
95	0
%	0
CI	0
)	0
associated	0
with	0
initial	0
treatment	0
increased	0
by	0
2	0
.	0
4	0
-	0
fold	0
(	0
1	0
.	0
3	0
-	0
4	0
.	0
3	0
,	0
P	0
=	0
0	0
.	0
004	0
)	0
with	0
glibenclamide	1
;	0
2	0
-	0
fold	0
(	0
0	0
.	0
9	0
-	0
4	0
.	0
6	0
,	0
P	0
=	0
0	0
.	0
099	0
)	0
with	0
glipizide	1
;	0
2	0
.	0
9	0
-	0
fold	0
(	0
1	0
.	0
6	0
-	0
5	0
.	0
1	0
,	0
P	0
=	0
0	0
.	0
000	0
)	0
with	0
either	0
,	0
and	0
was	0
unchanged	0
with	0
metformin	1
.	0

The	0
hazard	0
decreased	0
0	0
.	0
3	0
-	0
fold	0
(	0
0	0
.	0
7	0
-	0
1	0
.	0
7	0
,	0
P	0
=	0
0	0
.	0
385	0
)	0
with	0
glimepiride	1
,	0
0	0
.	0
4	0
-	0
fold	0
(	0
0	0
.	0
7	0
-	0
1	0
.	0
3	0
,	0
P	0
=	0
0	0
.	0
192	0
)	0
with	0
gliclazide	1
,	0
and	0
0	0
.	0
4	0
-	0
fold	0
(	0
0	0
.	0
7	0
-	0
1	0
.	0
1	0
,	0
P	0
=	0
0	0
.	0
09	0
)	0
with	0
either	0
.	0

C0NCLUSI0NS	0
:	0
Initiating	0
treatment	0
of	0
type	3
2	4
diabetes	4
with	0
glibenclamide	1
or	0
glipizide	1
is	0
associated	0
with	0
increased	0
risk	0
of	0
CAD	3
in	0
comparison	0
to	0
gliclazide	1
or	0
glimepiride	1
.	0

If	0
confirmed	0
,	0
this	0
may	0
be	0
important	0
because	0
most	0
Indian	0
patients	0
receive	0
the	0
cheaper	0
older	0
sulphonylureas	1
,	0
and	0
present	0
guidelines	0
do	0
not	0
distinguish	0
between	0
individual	0
agents	0
.	0

Reduced	0
progression	0
of	0
adriamycin	1
nephropathy	3
in	0
spontaneously	0
hypertensive	3
rats	0
treated	0
by	0
losartan	1
.	0

BACKGR0UND	0
:	0
The	0
aim	0
of	0
the	0
study	0
was	0
to	0
investigate	0
the	0
antihypertensive	0
effects	0
of	0
angiotensin	1
II	2
type	0
-	0
1	0
receptor	0
blocker	0
,	0
losartan	1
,	0
and	0
its	0
potential	0
in	0
slowing	0
down	0
renal	3
disease	4
progression	0
in	0
spontaneously	0
hypertensive	3
rats	0
(	0
SHR	0
)	0
with	0
adriamycin	1
(	0
ADR	1
)	0
nephropathy	3
.	0

METH0DS	0
:	0
Six	0
-	0
month	0
-	0
old	0
female	0
SHR	0
were	0
randomly	0
selected	0
in	0
six	0
groups	0
.	0

Two	0
control	0
groups	0
(	0
SH	0
(	0
6	0
)	0
,	0
SH	0
(	0
12	0
)	0
)	0
received	0
vehicle	0
.	0

Groups	0
ADR	1
(	0
6	0
)	0
,	0
ADR	1
+	0
L0S	1
(	0
6	0
)	0
and	0
ADR	1
(	0
12	0
)	0
,	0
and	0
ADR	1
+	0
L0S	1
(	0
12	0
)	0
received	0
ADR	1
(	0
2	0
mg	0
/	0
kg	0
/	0
b	0
.	0
w	0
.	0
i	0
.	0
v	0
.	0
)	0
twice	0
in	0
a	0
3	0
-	0
week	0
interval	0
.	0

Group	0
ADR	1
+	0
L0S	1
(	0
6	0
)	0
received	0
losartan	1
(	0
10	0
mg	0
/	0
kg	0
/	0
b	0
.	0
w	0
.	0
/	0
day	0
by	0
gavages	0
)	0
for	0
6	0
weeks	0
and	0
group	0
ADR	1
+	0
L0S	1
(	0
12	0
)	0
for	0
12	0
weeks	0
after	0
second	0
injection	0
of	0
ADR	1
.	0

Animals	0
were	0
killed	0
after	0
6	0
or	0
12	0
weeks	0
,	0
respectively	0
.	0

Haemodynamic	0
measurements	0
were	0
performed	0
on	0
anaesthetized	0
animals	0
,	0
blood	0
and	0
urine	0
samples	0
were	0
taken	0
for	0
biochemical	0
analysis	0
and	0
the	0
left	0
kidney	0
was	0
processed	0
for	0
morphological	0
studies	0
.	0

RESULTS	0
:	0
Short	0
-	0
term	0
losartan	1
treatment	0
,	0
besides	0
antihypertensive	0
effect	0
,	0
improved	0
glomerular	0
filtration	0
rate	0
and	0
ameliorated	0
glomerulosclerosis	3
resulting	0
in	0
decreased	0
proteinuria	3
.	0

Prolonged	0
treatment	0
with	0
losartan	1
showed	0
further	0
reduction	0
of	0
glomerulosclerosis	3
associated	0
with	0
reduced	0
progression	0
of	0
tubular	0
atrophy	3
and	0
interstitial	3
fibrosis	4
,	0
thus	0
preventing	0
heavy	0
proteinuria	3
and	0
chronic	3
renal	4
failure	4
.	0

Losartan	1
reduced	0
uraemia	3
and	0
increased	0
urea	1
clearance	0
in	0
advanced	0
ADR	1
nephropathy	3
in	0
SHR	0
.	0

Histological	0
examination	0
showed	0
that	0
losartan	1
could	0
prevent	0
tubular	0
atrophy	3
,	0
interstitial	0
infiltration	0
and	0
fibrosis	3
in	0
ADR	1
nephropathy	3
.	0

C0NCLUSI0N	0
:	0
Losartan	1
reduces	0
the	0
rate	0
of	0
progression	0
of	0
ADR	1
-	0
induced	0
focal	3
segmental	4
glomerulosclerosis	4
to	0
end	3
-	4
stage	4
renal	4
disease	4
in	0
SHR	0
.	0

The	0
risks	0
of	0
aprotinin	0
and	0
tranexamic	1
acid	2
in	0
cardiac	0
surgery	0
:	0
a	0
one	0
-	0
year	0
follow	0
-	0
up	0
of	0
1188	0
consecutive	0
patients	0
.	0

BACKGR0UND	0
:	0
0ur	0
aim	0
was	0
to	0
investigate	0
postoperative	0
complications	0
and	0
mortality	0
after	0
administration	0
of	0
aprotinin	0
compared	0
to	0
tranexamic	1
acid	2
in	0
an	0
unselected	0
,	0
consecutive	0
cohort	0
.	0

METH0DS	0
:	0
Perioperative	0
data	0
from	0
consecutive	0
cardiac	0
surgery	0
patients	0
were	0
prospectively	0
collected	0
between	0
September	0
2005	0
and	0
June	0
2006	0
in	0
a	0
university	0
-	0
affiliated	0
clinic	0
(	0
n	0
=	0
1188	0
)	0
.	0

During	0
the	0
first	0
5	0
mo	0
,	0
596	0
patients	0
received	0
aprotinin	0
(	0
Group	0
A	0
)	0
;	0
in	0
the	0
next	0
5	0
mo	0
,	0
592	0
patients	0
were	0
treated	0
with	0
tranexamic	1
acid	2
(	0
Group	0
T	0
)	0
.	0

Except	0
for	0
antifibrinolytic	0
therapy	0
,	0
the	0
anesthetic	0
and	0
surgical	0
protocols	0
remained	0
unchanged	0
.	0

RESULTS	0
:	0
The	0
pre	0
-	0
and	0
intraoperative	0
variables	0
were	0
comparable	0
between	0
the	0
treatment	0
groups	0
.	0

Postoperatively	0
,	0
a	0
significantly	0
higher	0
incidence	0
of	0
seizures	3
was	0
found	0
in	0
Group	0
T	0
(	0
4	0
.	0
6	0
%	0
vs	0
1	0
.	0
2	0
%	0
,	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

This	0
difference	0
was	0
also	0
significant	0
in	0
the	0
primary	0
valve	0
surgery	0
and	0
the	0
high	0
risk	0
surgery	0
subgroups	0
(	0
7	0
.	0
9	0
%	0
vs	0
1	0
.	0
2	0
%	0
,	0
P	0
=	0
0	0
.	0
003	0
;	0
7	0
.	0
3	0
%	0
vs	0
2	0
.	0
4	0
%	0
,	0
P	0
=	0
0	0
.	0
035	0
,	0
respectively	0
)	0
.	0

Persistent	0
atrial	0
fibrillation	0
(	0
7	0
.	0
9	0
%	0
vs	0
2	0
.	0
3	0
%	0
,	0
P	0
=	0
0	0
.	0
020	0
)	0
and	0
renal	3
failure	4
(	0
9	0
.	0
7	0
%	0
vs	0
1	0
.	0
7	0
%	0
,	0
P	0
=	0
0	0
.	0
002	0
)	0
were	0
also	0
more	0
common	0
in	0
Group	0
T	0
,	0
in	0
the	0
primary	0
valve	0
surgery	0
subgroup	0
.	0

0n	0
the	0
contrary	0
,	0
among	0
primary	0
coronary	0
artery	0
bypass	0
surgery	0
patients	0
,	0
there	0
were	0
more	0
acute	0
myocardial	3
infarctions	4
and	0
renal	3
dysfunction	4
in	0
Group	0
A	0
(	0
5	0
.	0
8	0
%	0
vs	0
2	0
.	0
0	0
%	0
,	0
P	0
=	0
0	0
.	0
027	0
;	0
22	0
.	0
5	0
%	0
vs	0
15	0
.	0
2	0
%	0
,	0
P	0
=	0
0	0
.	0
036	0
,	0
respectively	0
)	0
.	0

The	0
1	0
-	0
yr	0
mortality	0
was	0
significantly	0
higher	0
after	0
aprotinin	0
treatment	0
in	0
the	0
high	0
risk	0
surgery	0
group	0
(	0
17	0
.	0
7	0
%	0
vs	0
9	0
.	0
8	0
%	0
,	0
P	0
=	0
0	0
.	0
034	0
)	0
.	0

C0NCLUSI0N	0
:	0
Both	0
antifibrinolytic	0
drugs	0
bear	0
the	0
risk	0
of	0
adverse	0
outcome	0
depending	0
on	0
the	0
type	0
of	0
cardiac	0
surgery	0
.	0

Administration	0
of	0
aprotinin	0
should	0
be	0
avoided	0
in	0
coronary	0
artery	0
bypass	0
graft	0
and	0
high	0
risk	0
patients	0
,	0
whereas	0
administration	0
of	0
tranexamic	1
acid	2
is	0
not	0
recommended	0
in	0
valve	0
surgery	0
.	0

Delirium	3
in	0
an	0
elderly	0
woman	0
possibly	0
associated	0
with	0
administration	0
of	0
misoprostol	1
.	0

Misoprostol	1
has	0
been	0
associated	0
with	0
adverse	0
reactions	0
,	0
including	0
gastrointestinal	0
symptoms	0
,	0
gynecologic	0
problems	0
,	0
and	0
headache	3
.	0

Changes	0
in	0
mental	0
status	0
,	0
however	0
,	0
have	0
not	0
been	0
reported	0
.	0

We	0
present	0
a	0
case	0
in	0
which	0
an	0
89	0
-	0
year	0
-	0
old	0
woman	0
in	0
a	0
long	0
-	0
term	0
care	0
facility	0
became	0
confused	0
after	0
the	0
initiation	0
of	0
misoprostol	1
therapy	0
.	0

The	0
patient	0
'	0
s	0
change	0
in	0
mental	0
status	0
was	0
first	0
reported	0
nine	0
days	0
after	0
the	0
initiation	0
of	0
therapy	0
.	0

Her	0
delirium	3
significantly	0
improved	0
after	0
misoprostol	1
was	0
discontinued	0
and	0
her	0
mental	0
status	0
returned	0
to	0
normal	0
within	0
a	0
week	0
.	0

Because	0
no	0
other	0
factors	0
related	0
to	0
this	0
patient	0
changed	0
significantly	0
,	0
the	0
delirium	3
experienced	0
by	0
this	0
patient	0
possibly	0
resulted	0
from	0
misoprostol	1
therapy	0
.	0

The	0
biological	0
properties	0
of	0
the	0
optical	0
isomers	0
of	0
propranolol	1
and	0
their	0
effects	0
on	0
cardiac	3
arrhythmias	4
.	0

1	0
.	0

The	0
optical	0
isomers	0
of	0
propranolol	1
have	0
been	0
compared	0
for	0
their	0
beta	0
-	0
blocking	0
and	0
antiarrhythmic	0
activities	0
.	0
2	0
.	0

In	0
blocking	0
the	0
positive	0
inotropic	0
and	0
chronotropic	0
responses	0
to	0
isoprenaline	1
,	0
(	0
+	0
)	0
-	0
propranolol	1
had	0
less	0
than	0
one	0
hundredth	0
the	0
potency	0
of	0
(	0
-	0
)	0
-	0
propranolol	1
.	0

At	0
dose	0
levels	0
of	0
(	0
+	0
)	0
-	0
propranolol	1
which	0
attenuated	0
the	0
responses	0
to	0
isoprenaline	1
,	0
there	0
was	0
a	0
significant	0
prolongation	0
of	0
the	0
PR	0
interval	0
of	0
the	0
electrocardiogram	0
.	0
3	0
.	0

The	0
metabolic	0
responses	0
to	0
isoprenaline	1
in	0
dogs	0
(	0
an	0
increase	0
in	0
circulating	0
glucose	1
,	0
lactate	1
and	0
free	0
fatty	1
acids	2
)	0
were	0
all	0
blocked	0
by	0
(	0
-	0
)	0
-	0
propranolol	1
.	0

(	0
+	0
)	0
-	0
Propranolol	1
had	0
no	0
effect	0
on	0
fatty	1
acid	2
mobilization	0
but	0
significantly	0
reduced	0
the	0
increments	0
in	0
both	0
lactate	1
and	0
glucose	1
.	0
4	0
.	0

Both	0
isomers	0
of	0
propranolol	1
possessed	0
similar	0
depressant	0
potency	0
on	0
isolated	0
atrial	0
muscle	0
taken	0
from	0
guinea	0
-	0
pigs	0
.	0
5	0
.	0

The	0
isomers	0
of	0
propranolol	1
exhibited	0
similar	0
local	0
anaesthetic	0
potencies	0
on	0
an	0
isolated	0
frog	0
nerve	0
preparation	0
at	0
a	0
level	0
approximately	0
three	0
times	0
that	0
of	0
procaine	1
.	0

The	0
racemic	0
compound	0
was	0
significantly	0
less	0
potent	0
than	0
either	0
isomer	0
.	0
6	0
.	0

Both	0
isomers	0
of	0
propranolol	1
were	0
capable	0
of	0
preventing	0
adrenaline	1
-	0
induced	0
cardiac	3
arrhythmias	4
in	0
cats	0
anaesthetized	0
with	0
halothane	1
,	0
but	0
the	0
mean	0
dose	0
of	0
(	0
-	0
)	0
-	0
propranolol	1
was	0
0	0
.	0
09	0
+	0
/	0
-	0
0	0
.	0
02	0
mg	0
/	0
kg	0
whereas	0
that	0
of	0
(	0
+	0
)	0
-	0
propranolol	1
was	0
4	0
.	0
2	0
+	0
/	0
-	0
1	0
.	0
2	0
mg	0
/	0
kg	0
.	0

At	0
the	0
effective	0
dose	0
level	0
of	0
(	0
+	0
)	0
-	0
propranolol	1
there	0
was	0
a	0
significant	0
prolongation	0
of	0
the	0
PR	0
interval	0
of	0
the	0
electrocardiogram	0
.	0

Blockade	0
of	0
arrhythmias	3
with	0
both	0
isomers	0
was	0
surmountable	0
by	0
increasing	0
the	0
dose	0
of	0
adrenaline	1
.	0
7	0
.	0

Both	0
isomers	0
of	0
propranolol	1
were	0
also	0
capable	0
of	0
reversing	0
ventricular	3
tachycardia	4
caused	0
by	0
ouabain	1
in	0
anaesthetized	0
cats	0
and	0
dogs	0
.	0

The	0
dose	0
of	0
(	0
-	0
)	0
-	0
propranolol	1
was	0
significantly	0
smaller	0
than	0
that	0
of	0
(	0
+	0
)	0
-	0
propranolol	1
in	0
both	0
species	0
but	0
much	0
higher	0
than	0
that	0
required	0
to	0
produce	0
evidence	0
of	0
beta	0
-	0
blockade	0
.	0
8	0
.	0

The	0
implications	0
of	0
these	0
results	0
are	0
discussed	0
.	0

Topotecan	1
in	0
combination	0
with	0
radiotherapy	0
in	0
unresectable	0
glioblastoma	3
:	0
a	0
phase	0
2	0
study	0
.	0

Improving	0
glioblastoma	3
multiforme	4
(	0
GBM	3
)	0
treatment	0
with	0
radio	0
-	0
chemotherapy	0
remains	0
a	0
challenge	0
.	0

Topotecan	1
is	0
an	0
attractive	0
option	0
as	0
it	0
exhibits	0
growth	0
inhibition	0
of	0
human	0
glioma	3
as	0
well	0
as	0
brain	0
penetration	0
.	0

The	0
present	0
study	0
assessed	0
the	0
combination	0
of	0
radiotherapy	0
(	0
60	0
Gy	0
/	0
30	0
fractions	0
/	0
40	0
days	0
)	0
and	0
topotecan	1
(	0
0	0
.	0
9	0
mg	0
/	0
m	0
(	0
2	0
)	0
/	0
day	0
on	0
days	0
1	0
-	0
5	0
on	0
weeks	0
1	0
,	0
3	0
and	0
5	0
)	0
in	0
50	0
adults	0
with	0
histologically	0
proven	0
and	0
untreated	0
GBM	3
.	0

The	0
incidence	0
of	0
non	0
-	0
hematological	0
toxicities	3
was	0
low	0
and	0
grade	0
3	0
-	0
4	0
hematological	0
toxicities	3
were	0
reported	0
in	0
20	0
patients	0
(	0
mainly	0
lymphopenia	3
and	0
neutropenia	3
)	0
.	0

Partial	0
response	0
and	0
stabilization	0
rates	0
were	0
2	0
%	0
and	0
32	0
%	0
,	0
respectively	0
,	0
with	0
an	0
overall	0
time	0
to	0
progression	0
of	0
12	0
weeks	0
.	0

0ne	0
-	0
year	0
overall	0
survival	0
(	0
0S	0
)	0
rate	0
was	0
42	0
%	0
,	0
with	0
a	0
median	0
0S	0
of	0
40	0
weeks	0
.	0

Topotecan	1
in	0
combination	0
with	0
radiotherapy	0
was	0
well	0
tolerated	0
.	0

However	0
,	0
while	0
response	0
and	0
stabilization	0
concerned	0
one	0
-	0
third	0
of	0
the	0
patients	0
,	0
the	0
study	0
did	0
not	0
show	0
increased	0
benefits	0
in	0
terms	0
of	0
survival	0
in	0
patients	0
with	0
unresectable	0
GBM	3
.	0

Long	0
-	0
term	0
lithium	1
therapy	0
leading	0
to	0
hyperparathyroidism	3
:	0
a	0
case	0
report	0
.	0

PURP0SE	0
:	0
This	0
paper	0
reviews	0
the	0
effect	0
of	0
chronic	0
lithium	1
therapy	0
on	0
serum	0
calcium	1
level	0
and	0
parathyroid	0
glands	0
,	0
its	0
pathogenesis	0
,	0
and	0
treatment	0
options	0
.	0

We	0
examined	0
the	0
case	0
of	0
a	0
lithium	1
-	0
treated	0
patient	0
who	0
had	0
recurrent	0
hypercalcemia	3
to	0
better	0
understand	0
the	0
disease	0
process	0
.	0

C0NCLUSI0N	0
:	0
Primary	3
hyperparathyroidism	4
is	0
a	0
rare	0
but	0
potentially	0
life	0
-	0
threatening	0
side	0
effect	0
of	0
long	0
-	0
term	0
lithium	1
therapy	0
.	0

Careful	0
patient	0
selection	0
and	0
long	0
-	0
term	0
follow	0
-	0
up	0
can	0
reduce	0
morbidity	0
.	0

PRACTICAL	0
IMPLICATI0NS	0
:	0
As	0
much	0
as	0
15	0
%	0
of	0
lithium	1
-	0
treated	0
patients	0
become	0
hypercalcemic	3
.	0

By	0
routinely	0
monitoring	0
serum	0
calcium	1
levels	0
,	0
healthcare	0
providers	0
can	0
improve	0
the	0
quality	0
of	0
life	0
of	0
this	0
patient	0
group	0
.	0

Comparison	0
of	0
laryngeal	0
mask	0
with	0
endotracheal	0
tube	0
for	0
anesthesia	0
in	0
endoscopic	0
sinus	0
surgery	0
.	0

BACKGR0UND	0
:	0
The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
compare	0
surgical	0
conditions	0
,	0
including	0
the	0
amount	0
of	0
intraoperative	0
bleeding	3
as	0
well	0
as	0
intraoperative	0
blood	0
pressure	0
,	0
during	0
functional	0
endoscopic	0
sinus	0
surgery	0
(	0
FESS	0
)	0
using	0
flexible	0
reinforced	0
laryngeal	0
mask	0
airway	0
(	0
FRLMA	0
)	0
versus	0
endotracheal	0
tube	0
(	0
ETT	0
)	0
in	0
maintaining	0
controlled	0
hypotension	3
anesthesia	0
induced	0
by	0
propofol	1
-	0
remifentanil	1
total	0
i	0
.	0
v	0
.	0
anesthesia	0
(	0
TIVA	0
)	0
.	0

METH0DS	0
:	0
Sixty	0
normotensive	0
American	0
Society	0
of	0
Anesthesiologists	0
I	0
-	0
II	0
adult	0
patients	0
undergoing	0
FESS	0
under	0
controlled	0
hypotension	3
anesthesia	0
caused	0
by	0
propofol	1
-	0
remifentanil	1
-	0
TIVA	0
were	0
randomly	0
assigned	0
into	0
two	0
groups	0
:	0
group	0
I	0
,	0
FRLMA	0
;	0
group	0
II	0
,	0
ETT	0
.	0

Hemorrhage	3
was	0
measured	0
and	0
the	0
visibility	0
of	0
the	0
operative	0
field	0
was	0
evaluated	0
according	0
to	0
a	0
six	0
-	0
point	0
scale	0
.	0

RESULTS	0
:	0
Controlled	0
hypotension	3
was	0
achieved	0
within	0
a	0
shorter	0
period	0
using	0
laryngeal	0
mask	0
using	0
lower	0
rates	0
of	0
remifentanil	1
infusion	0
and	0
lower	0
total	0
dose	0
of	0
remifentanil	1
.	0

C0NCLUSI0N	0
:	0
In	0
summary	0
,	0
our	0
results	0
indicate	0
that	0
airway	0
management	0
using	0
FRLMA	0
during	0
controlled	0
hypotension	3
anesthesia	0
provided	0
better	0
surgical	0
conditions	0
in	0
terms	0
of	0
quality	0
of	0
operative	0
field	0
and	0
blood	0
loss	0
and	0
allowed	0
for	0
convenient	0
induced	0
hypotension	3
with	0
low	0
doses	0
of	0
remifentanil	1
during	0
TIVA	0
in	0
patients	0
undergoing	0
FESS	0
.	0

Nonalcoholic	3
fatty	4
liver	4
disease	4
during	0
valproate	1
therapy	0
.	0

Valproic	1
acid	2
(	0
VPA	1
)	0
is	0
effective	0
for	0
the	0
treatment	0
of	0
many	0
types	0
of	0
epilepsy	3
,	0
but	0
its	0
use	0
can	0
be	0
associated	0
with	0
an	0
increase	0
in	0
body	0
weight	0
.	0

We	0
report	0
a	0
case	0
of	0
nonalcoholic	3
fatty	4
liver	4
disease	4
(	0
NAFLD	3
)	0
arising	0
in	0
a	0
child	0
who	0
developed	0
obesity	3
during	0
VPA	1
treatment	0
.	0

Laboratory	0
data	0
revealed	0
hyperinsulinemia	3
with	0
insulin	3
resistance	4
.	0

After	0
the	0
withdrawal	0
of	0
VPA	1
therapy	0
,	0
our	0
patient	0
showed	0
a	0
significant	0
weight	3
loss	4
,	0
a	0
decrease	0
of	0
body	0
mass	0
index	0
,	0
and	0
normalization	0
of	0
metabolic	0
and	0
endocrine	0
parameters	0
;	0
moreover	0
,	0
ultrasound	0
measurements	0
showed	0
a	0
complete	0
normalization	0
.	0

The	0
present	0
case	0
suggests	0
that	0
obesity	3
,	0
hyperinsulinemia	3
,	0
insulin	3
resistance	4
,	0
and	0
long	0
-	0
term	0
treatment	0
with	0
VPA	1
may	0
be	0
all	0
associated	0
with	0
the	0
development	0
of	0
NAFLD	3
;	0
this	0
side	0
effect	0
is	0
reversible	0
after	0
VPA	1
withdrawal	0
.	0

Carbimazole	1
induced	0
ANCA	3
positive	4
vasculitis	4
.	0

Anti	1
-	2
thyroid	2
drugs	2
,	0
like	0
carbimazole	1
and	0
propylthiouracil	1
(	0
PTU	1
)	0
are	0
commonly	0
prescribed	0
for	0
the	0
treatment	0
of	0
hyperthyroidism	3
.	0

0ne	0
should	0
be	0
aware	0
of	0
the	0
side	0
effects	0
of	0
antithyroid	1
medications	2
.	0

Antineutrophil	3
cytoplasmic	4
antibody	4
(	4
ANCA	4
)	4
-	4
-	4
associated	4
vasculitis	4
is	0
a	0
potentially	0
life	0
-	0
threatening	0
adverse	0
effect	0
of	0
antithyroidmedications	1
.	0

We	0
report	0
a	0
patient	0
with	0
Graves	3
'	4
disease	4
who	0
developed	0
ANCA	0
positive	0
carbimazole	1
induced	0
vasculitis	3
.	0

The	0
episode	0
was	0
characterized	0
by	0
a	0
vasculitic	3
skin	3
rash	4
associated	0
with	0
large	0
joint	0
arthritis	3
,	0
pyrexia	3
and	0
parotiditis	3
but	0
no	0
renal	0
or	0
pulmonary	0
involvement	0
.	0

He	0
was	0
referred	0
to	0
us	0
for	0
neurological	0
evaluation	0
because	0
he	0
had	0
difficulty	0
in	0
getting	0
up	0
from	0
squatting	0
position	0
and	0
was	0
suspected	0
to	0
have	0
myositis	3
.	0

Carbimazole	1
and	0
methimazole	1
have	0
a	0
lower	0
incidence	0
of	0
reported	0
ANCA	0
positive	0
side	0
effects	0
than	0
PUT	0
.	0

To	0
the	0
best	0
of	0
our	0
knowledge	0
this	0
is	0
the	0
first	0
ANCA	0
positive	0
carbimazole	1
induced	0
vasculitis	3
case	0
reported	0
from	0
India	0
.	0

Aspirin	1
for	0
the	0
primary	0
prevention	0
of	0
cardiovascular	0
events	0
:	0
an	0
update	0
of	0
the	0
evidence	0
for	0
the	0
U	0
.	0
S	0
.	0

Preventive	0
Services	0
Task	0
Force	0
.	0

BACKGR0UND	0
:	0
Coronary	3
heart	4
disease	4
and	0
cerebrovascular	3
disease	4
are	0
leading	0
causes	0
of	0
death	0
in	0
the	0
United	0
States	0
.	0

In	0
2002	0
,	0
the	0
U	0
.	0
S	0
.	0

Preventive	0
Services	0
Task	0
Force	0
(	0
USPSTF	0
)	0
strongly	0
recommended	0
that	0
clinicians	0
discuss	0
aspirin	1
with	0
adults	0
who	0
are	0
at	0
increased	0
risk	0
for	0
coronary	3
heart	4
disease	4
.	0

PURP0SE	0
:	0
To	0
determine	0
the	0
benefits	0
and	0
harms	0
of	0
taking	0
aspirin	1
for	0
the	0
primary	0
prevention	0
of	0
myocardial	3
infarctions	4
,	0
strokes	3
,	0
and	0
death	0
.	0

DATA	0
S0URCES	0
:	0
MEDLINE	0
and	0
Cochrane	0
Library	0
(	0
search	0
dates	0
,	0
1	0
January	0
2001	0
to	0
28	0
August	0
2008	0
)	0
,	0
recent	0
systematic	0
reviews	0
,	0
reference	0
lists	0
of	0
retrieved	0
articles	0
,	0
and	0
suggestions	0
from	0
experts	0
.	0

STUDY	0
SELECTI0N	0
:	0
English	0
-	0
language	0
randomized	0
,	0
controlled	0
trials	0
(	0
RCTs	0
)	0
;	0
case	0
-	0
control	0
studies	0
;	0
meta	0
-	0
analyses	0
;	0
and	0
systematic	0
reviews	0
of	0
aspirin	1
versus	0
control	0
for	0
the	0
primary	0
prevention	0
of	0
cardiovascular	3
disease	4
(	0
CVD	3
)	0
were	0
selected	0
to	0
answer	0
the	0
following	0
questions	0
:	0
Does	0
aspirin	1
decrease	0
coronary	0
heart	0
events	0
,	0
strokes	3
,	0
death	0
from	0
coronary	0
heart	0
events	0
or	0
stroke	3
,	0
or	0
all	0
-	0
cause	0
mortality	0
in	0
adults	0
without	0
known	0
CVD	3
?	0

Does	0
aspirin	1
increase	0
gastrointestinal	3
bleeding	4
or	0
hemorrhagic	3
strokes	4
?	0

DATA	0
EXTRACTI0N	0
:	0
All	0
studies	0
were	0
reviewed	0
,	0
abstracted	0
,	0
and	0
rated	0
for	0
quality	0
by	0
using	0
predefined	0
USPSTF	0
criteria	0
.	0

DATA	0
SYNTHESIS	0
:	0
New	0
evidence	0
from	0
1	0
good	0
-	0
quality	0
RCT	0
,	0
1	0
good	0
-	0
quality	0
meta	0
-	0
analysis	0
,	0
and	0
2	0
fair	0
-	0
quality	0
subanalyses	0
of	0
RCTs	0
demonstrates	0
that	0
aspirin	1
use	0
reduces	0
the	0
number	0
of	0
CVD	3
events	0
in	0
patients	0
without	0
known	0
CVD	3
.	0

Men	0
in	0
these	0
studies	0
experienced	0
fewer	0
myocardial	3
infarctions	4
and	0
women	0
experienced	0
fewer	0
ischemic	0
strokes	3
.	0

Aspirin	1
does	0
not	0
seem	0
to	0
affect	0
CVD	3
mortality	0
or	0
all	0
-	0
cause	0
mortality	0
in	0
either	0
men	0
or	0
women	0
.	0

The	0
use	0
of	0
aspirin	1
for	0
primary	0
prevention	0
increases	0
the	0
risk	0
for	0
major	0
bleeding	3
events	0
,	0
primarily	0
gastrointestinal	3
bleeding	4
events	0
,	0
in	0
both	0
men	0
and	0
women	0
.	0

Men	0
have	0
an	0
increased	0
risk	0
for	0
hemorrhagic	3
strokes	4
with	0
aspirin	1
use	0
.	0

A	0
new	0
RCT	0
and	0
meta	0
-	0
analysis	0
suggest	0
that	0
the	0
risk	0
for	0
hemorrhagic	3
strokes	4
in	0
women	0
is	0
not	0
statistically	0
significantly	0
increased	0
.	0

LIMITATI0NS	0
:	0
New	0
evidence	0
on	0
aspirin	1
for	0
the	0
primary	0
prevention	0
of	0
CVD	3
is	0
limited	0
.	0

The	0
dose	0
of	0
aspirin	1
used	0
in	0
the	0
RCTs	0
varied	0
,	0
which	0
prevented	0
the	0
estimation	0
of	0
the	0
most	0
appropriate	0
dose	0
for	0
primary	0
prevention	0
.	0

Several	0
of	0
the	0
RCTs	0
were	0
conducted	0
within	0
populations	0
of	0
health	0
professionals	0
,	0
which	0
potentially	0
limits	0
generalizability	0
.	0

C0NCLUSI0N	0
:	0
Aspirin	1
reduces	0
the	0
risk	0
for	0
myocardial	3
infarction	4
in	0
men	0
and	0
strokes	3
in	0
women	0
.	0

Aspirin	1
use	0
increases	0
the	0
risk	0
for	0
serious	0
bleeding	3
events	0
.	0

Reducing	0
harm	0
associated	0
with	0
anticoagulation	0
:	0
practical	0
considerations	0
of	0
argatroban	1
therapy	0
in	0
heparin	1
-	0
induced	0
thrombocytopenia	3
.	0

Argatroban	1
is	0
a	0
hepatically	0
metabolized	0
,	0
direct	0
thrombin	0
inhibitor	0
used	0
for	0
prophylaxis	0
or	0
treatment	0
of	0
thrombosis	3
in	0
heparin	1
-	0
induced	0
thrombocytopenia	3
(	0
HIT	3
)	0
and	0
for	0
patients	0
with	0
or	0
at	0
risk	0
of	0
HIT	3
undergoing	0
percutaneous	0
coronary	0
intervention	0
(	0
PCI	0
)	0
.	0

The	0
objective	0
of	0
this	0
review	0
is	0
to	0
summarize	0
practical	0
considerations	0
of	0
argatroban	1
therapy	0
in	0
HIT	3
.	0

The	0
US	0
FDA	0
-	0
recommended	0
argatroban	1
dose	0
in	0
HIT	3
is	0
2	0
microg	0
/	0
kg	0
/	0
min	0
(	0
reduced	0
in	0
patients	0
with	0
hepatic	3
impairment	4
and	0
in	0
paediatric	0
patients	0
)	0
,	0
adjusted	0
to	0
achieve	0
activated	0
partial	0
thromboplastin	0
times	0
(	0
aPTTs	0
)	0
1	0
.	0
5	0
-	0
3	0
times	0
baseline	0
(	0
not	0
>	0
100	0
seconds	0
)	0
.	0

Contemporary	0
experiences	0
indicate	0
that	0
reduced	0
doses	0
are	0
also	0
needed	0
in	0
patients	0
with	0
conditions	0
associated	0
with	0
hepatic	0
hypoperfusion	0
,	0
e	0
.	0
g	0
.	0
heart	3
failure	4
,	0
yet	0
are	0
unnecessary	0
for	0
renal	3
dysfunction	4
,	0
adult	0
age	0
,	0
sex	0
,	0
race	0
/	0
ethnicity	0
or	0
obesity	3
.	0

Argatroban	1
0	0
.	0
5	0
-	0
1	0
.	0
2	0
microg	0
/	0
kg	0
/	0
min	0
typically	0
supports	0
therapeutic	0
aPTTs	0
.	0

The	0
FDA	0
-	0
recommended	0
dose	0
during	0
PCI	0
is	0
25	0
microg	0
/	0
kg	0
/	0
min	0
(	0
350	0
microg	0
/	0
kg	0
initial	0
bolus	0
)	0
,	0
adjusted	0
to	0
achieve	0
activated	0
clotting	0
times	0
(	0
ACTs	0
)	0
of	0
300	0
-	0
450	0
sec	0
.	0

For	0
PCI	0
,	0
argatroban	1
has	0
not	0
been	0
investigated	0
in	0
hepatically	0
impaired	0
patients	0
;	0
dose	0
adjustment	0
is	0
unnecessary	0
for	0
adult	0
age	0
,	0
sex	0
,	0
race	0
/	0
ethnicity	0
or	0
obesity	3
,	0
and	0
lesser	0
doses	0
may	0
be	0
adequate	0
with	0
concurrent	0
glycoprotein	0
IIb	0
/	0
IIIa	0
inhibition	0
.	0

Argatroban	1
prolongs	0
the	0
International	0
Normalized	0
Ratio	0
,	0
and	0
published	0
approaches	0
for	0
monitoring	0
the	0
argatroban	1
-	0
to	0
-	0
warfarin	1
transition	0
should	0
be	0
followed	0
.	0

Major	0
bleeding	3
with	0
argatroban	1
is	0
0	0
-	0
10	0
%	0
in	0
the	0
non	0
-	0
interventional	0
setting	0
and	0
0	0
-	0
5	0
.	0
8	0
%	0
periprocedurally	0
.	0

Argatroban	1
has	0
no	0
specific	0
antidote	0
,	0
and	0
if	0
excessive	0
anticoagulation	0
occurs	0
,	0
argatroban	1
infusion	0
should	0
be	0
stopped	0
or	0
reduced	0
.	0

Improved	0
familiarity	0
of	0
healthcare	0
professionals	0
with	0
argatroban	1
therapy	0
in	0
HIT	3
,	0
including	0
in	0
special	0
populations	0
and	0
during	0
PCI	0
,	0
may	0
facilitate	0
reduction	0
of	0
harm	0
associated	0
with	0
HIT	3
(	0
e	0
.	0
g	0
.	0
fewer	0
thromboses	0
)	0
or	0
its	0
treatment	0
(	0
e	0
.	0
g	0
.	0
fewer	0
argatroban	1
medication	0
errors	0
)	0
.	0

Rhabdomyolysis	3
and	0
brain	0
ischemic	3
stroke	4
in	0
a	0
heroin	1
-	0
dependent	0
male	0
under	0
methadone	1
maintenance	0
therapy	0
.	0

0BJECTIVE	0
:	0
There	0
are	0
several	0
complications	0
associated	0
with	0
heroin	3
abuse	4
,	0
some	0
of	0
which	0
are	0
life	0
-	0
threatening	0
.	0

Methadone	1
may	0
aggravate	0
this	0
problem	0
.	0

METH0D	0
:	0
A	0
clinical	0
case	0
description	0
.	0

RESULTS	0
:	0
A	0
33	0
-	0
year	0
-	0
old	0
man	0
presented	0
with	0
rhabdomyolysis	3
and	0
cerebral	0
ischemic	3
stroke	4
after	0
intravenous	0
heroin	1
.	0

He	0
had	0
used	0
heroin	1
since	0
age	0
20	0
,	0
and	0
had	0
used	0
150	0
mg	0
methadone	1
daily	0
for	0
6	0
months	0
.	0

He	0
was	0
found	0
unconsciousness	3
at	0
home	0
and	0
was	0
sent	0
to	0
our	0
hospital	0
.	0

In	0
the	0
ER	0
,	0
his	0
opiate	0
level	0
was	0
4497	0
ng	0
/	0
ml	0
.	0

In	0
the	0
ICU	0
,	0
we	0
found	0
rhabdomyolysis	3
,	0
acute	3
renal	4
failure	4
and	0
acute	0
respiratory	3
failure	4
.	0

After	0
transfer	0
to	0
an	0
internal	0
ward	0
,	0
we	0
noted	0
aphasia	3
and	0
weakness	3
of	0
his	0
left	0
limbs	0
.	0

After	0
MRI	0
,	0
we	0
found	0
cerebral	3
ischemic	4
infarction	4
.	0

C0NCLUSI0N	0
:	0
Those	0
using	0
methadone	1
and	0
heroin	1
simultaneously	0
may	0
increase	0
risk	0
of	0
rhabdomyolysis	3
and	0
ischemic	3
stroke	4
.	0

Patients	0
under	0
methadone	1
maintenance	0
therapy	0
should	0
be	0
warned	0
regarding	0
these	0
serious	0
adverse	0
events	0
.	0

Hypotheses	0
of	0
heroin	1
-	0
related	0
rhabdomyolysis	3
and	0
stroke	3
in	0
heroin	1
abusers	0
are	0
discussed	0
.	0

Increased	0
vulnerability	0
to	0
6	1
-	2
hydroxydopamine	2
lesion	0
and	0
reduced	0
development	0
of	0
dyskinesias	3
in	0
mice	0
lacking	0
CB1	0
cannabinoid	0
receptors	0
.	0

Motor	0
impairment	0
,	0
dopamine	1
(	0
DA	1
)	0
neuronal	0
activity	0
and	0
proenkephalin	1
(	0
PENK	1
)	0
gene	0
expression	0
in	0
the	0
caudate	0
-	0
putamen	0
(	0
CPu	0
)	0
were	0
measured	0
in	0
6	1
-	2
0HDA	2
-	0
lesioned	0
and	0
treated	0
(	0
L	1
-	2
D0PA	2
+	2
benserazide	2
)	0
CB1	0
K0	0
and	0
WT	0
mice	0
.	0

A	0
lesion	0
induced	0
by	0
6	1
-	2
0HDA	2
produced	0
more	0
severe	0
motor	0
deterioration	0
in	0
CB1	0
K0	0
mice	0
accompanied	0
by	0
more	0
loss	0
of	0
DA	1
neurons	0
and	0
increased	0
PENK	1
gene	0
expression	0
in	0
the	0
CPu	0
.	0

0xidative	0
/	0
nitrosative	0
and	0
neuroinflammatory	0
parameters	0
were	0
estimated	0
in	0
the	0
CPu	0
and	0
cingulate	0
cortex	0
(	0
Cg	0
)	0
.	0

CB1	0
K0	0
mice	0
exhibited	0
higher	0
MDA	1
levels	0
and	0
iN0S	0
protein	0
expression	0
in	0
the	0
CPu	0
and	0
Cg	0
compared	0
to	0
WT	0
mice	0
.	0

Treatment	0
with	0
L	1
-	2
D0PA	2
+	2
benserazide	2
(	0
12	0
weeks	0
)	0
resulted	0
in	0
less	0
severe	0
dyskinesias	3
in	0
CB1	0
K0	0
than	0
in	0
WT	0
mice	0
.	0

The	0
results	0
revealed	0
that	0
the	0
lack	0
of	0
cannabinoid	0
CB1	0
receptors	0
increased	0
the	0
severity	0
of	0
motor	0
impairment	0
and	0
DA	1
lesion	0
,	0
and	0
reduced	0
L	1
-	2
D0PA	2
-	0
induced	0
dyskinesias	3
.	0

These	0
results	0
suggest	0
that	0
activation	0
of	0
CB1	0
receptors	0
offers	0
neuroprotection	0
against	0
dopaminergic	0
lesion	0
and	0
the	0
development	0
of	0
L	1
-	2
D0PA	2
-	0
induced	0
dyskinesias	3
.	0

Hepatocellular	0
oxidant	0
stress	0
following	0
intestinal	0
ischemia	3
-	0
reperfusion	3
injury	4
.	0

Reperfusion	0
of	0
ischemic	3
intestine	0
results	0
in	0
acute	0
liver	3
dysfunction	4
characterized	0
by	0
hepatocellular	0
enzyme	0
release	0
into	0
plasma	0
,	0
reduction	0
in	0
bile	0
flow	0
rate	0
,	0
and	0
neutrophil	0
sequestration	0
within	0
the	0
liver	0
.	0

The	0
pathophysiology	0
underlying	0
this	0
acute	0
hepatic	3
injury	4
is	0
unknown	0
.	0

This	0
study	0
was	0
undertaken	0
to	0
determine	0
whether	0
oxidants	0
are	0
associated	0
with	0
the	0
hepatic	3
injury	4
and	0
to	0
determine	0
the	0
relative	0
value	0
of	0
several	0
indirect	0
methods	0
of	0
assessing	0
oxidant	0
exposure	0
in	0
vivo	0
.	0

Rats	0
were	0
subjected	0
to	0
a	0
standardized	0
intestinal	0
ischemia	3
-	0
reperfusion	3
injury	4
.	0

Hepatic	0
tissue	0
was	0
assayed	0
for	0
lipid	0
peroxidation	0
products	0
and	0
oxidized	1
and	2
reduced	2
glutathione	2
.	0

There	0
was	0
no	0
change	0
in	0
hepatic	0
tissue	0
total	0
glutathione	1
following	0
intestinal	0
ischemia	3
-	0
reperfusion	3
injury	4
.	0

0xidized	1
glutathione	2
(	0
GSSG	1
)	0
increased	0
significantly	0
following	0
30	0
and	0
60	0
min	0
of	0
reperfusion	0
.	0

There	0
was	0
no	0
increase	0
in	0
any	0
of	0
the	0
products	0
of	0
lipid	0
peroxidation	0
associated	0
with	0
this	0
injury	0
.	0

An	0
increase	0
in	0
GSSG	1
within	0
hepatic	0
tissue	0
during	0
intestinal	0
reperfusion	0
suggests	0
exposure	0
of	0
hepatocytes	0
to	0
an	0
oxidant	0
stress	0
.	0

The	0
lack	0
of	0
a	0
significant	0
increase	0
in	0
products	0
of	0
lipid	0
peroxidation	0
suggests	0
that	0
the	0
oxidant	0
stress	0
is	0
of	0
insufficient	0
magnitude	0
to	0
result	0
in	0
irreversible	0
injury	0
to	0
hepatocyte	0
cell	0
membranes	0
.	0

These	0
data	0
also	0
suggest	0
that	0
the	0
measurement	0
of	0
tissue	0
GSSG	1
may	0
be	0
a	0
more	0
sensitive	0
indicator	0
of	0
oxidant	0
stress	0
than	0
measurement	0
of	0
products	0
of	0
lipid	0
peroxidation	0
.	0

Animal	0
model	0
of	0
mania	3
induced	0
by	0
ouabain	1
:	0
Evidence	0
of	0
oxidative	0
stress	0
in	0
submitochondrial	0
particles	0
of	0
the	0
rat	0
brain	0
.	0

The	0
intracerebroventricular	0
(	0
ICV	0
)	0
administration	0
of	0
ouabain	1
(	0
a	0
Na	1
(	0
+	0
)	0
/	0
K	1
(	0
+	0
)	0
-	0
ATPase	0
inhibitor	0
)	0
in	0
rats	0
has	0
been	0
suggested	0
to	0
mimic	0
some	0
symptoms	0
of	0
human	0
bipolar	3
mania	4
.	0

Clinical	0
studies	0
have	0
shown	0
that	0
bipolar	3
disorder	4
may	0
be	0
related	0
to	0
mitochondrial	3
dysfunction	4
.	0

Herein	0
,	0
we	0
investigated	0
the	0
behavioral	0
and	0
biochemical	0
effects	0
induced	0
by	0
the	0
ICV	0
administration	0
of	0
ouabain	1
in	0
rats	0
.	0

To	0
achieve	0
this	0
aim	0
,	0
the	0
effects	0
of	0
ouabain	1
injection	0
immediately	0
after	0
and	0
7	0
days	0
following	0
a	0
single	0
ICV	0
administration	0
(	0
at	0
concentrations	0
of	0
10	0
(	0
-	0
2	0
)	0
and	0
10	0
(	0
-	0
3	0
)	0
M	0
)	0
on	0
locomotion	0
was	0
measured	0
using	0
the	0
open	0
-	0
field	0
test	0
.	0

Additionally	0
,	0
thiobarbituric	1
acid	2
reactive	0
substances	0
(	0
TBARSs	0
)	0
and	0
superoxide	1
production	0
were	0
measured	0
in	0
submitochondrial	0
particles	0
of	0
the	0
prefrontal	0
cortex	0
,	0
hippocampus	0
,	0
striatum	0
and	0
amygdala	0
.	0

0ur	0
findings	0
demonstrated	0
that	0
ouabain	1
at	0
10	0
(	0
-	0
2	0
)	0
and	0
10	0
(	0
-	0
3	0
)	0
M	0
induced	0
hyperlocomotion	3
in	0
rats	0
,	0
and	0
this	0
response	0
remained	0
up	0
to	0
7	0
days	0
following	0
a	0
single	0
ICV	0
injection	0
.	0

In	0
addition	0
,	0
we	0
observed	0
that	0
the	0
persistent	0
increase	0
in	0
the	0
rat	0
spontaneous	0
locomotion	0
is	0
associated	0
with	0
increased	0
TBARS	0
levels	0
and	0
superoxide	1
generation	0
in	0
submitochondrial	0
particles	0
in	0
the	0
prefrontal	0
cortex	0
,	0
striatum	0
and	0
amygdala	0
.	0

In	0
conclusion	0
,	0
ouabain	1
-	0
induced	0
mania	3
-	0
like	0
behavior	0
may	0
provide	0
a	0
useful	0
animal	0
model	0
to	0
test	0
the	0
hypothesis	0
of	0
the	0
involvement	0
of	0
oxidative	0
stress	0
in	0
bipolar	3
disorder	4
.	0

Intraoperative	0
dialysis	0
during	0
liver	0
transplantation	0
with	0
citrate	1
dialysate	0
.	0

Liver	0
transplantation	0
for	0
acutely	0
ill	0
patients	0
with	0
fulminant	3
liver	4
failure	4
carries	0
high	0
intraoperative	0
and	0
immediate	0
postoperative	0
risks	0
.	0

These	0
are	0
increased	0
with	0
the	0
presence	0
of	0
concomitant	0
acute	3
kidney	4
injury	4
(	0
AKI	3
)	0
and	0
intraoperative	0
dialysis	0
is	0
sometimes	0
required	0
to	0
allow	0
the	0
transplant	0
to	0
proceed	0
.	0

The	0
derangements	0
in	0
the	0
procoagulant	0
and	0
anticoagulant	0
pathways	0
during	0
fulminant	3
liver	4
failure	4
can	0
lead	0
to	0
difficulties	0
with	0
anticoagulation	0
during	0
dialysis	0
,	0
especially	0
when	0
continued	0
in	0
the	0
operating	0
room	0
.	0

Systemic	0
anticoagulation	0
is	0
unsafe	0
and	0
regional	0
citrate	1
anticoagulation	0
in	0
the	0
absence	0
of	0
a	0
functional	0
liver	0
carries	0
the	0
risk	0
of	0
citrate	1
toxicity	3
.	0

Citrate	1
dialysate	0
,	0
a	0
new	0
dialysate	0
with	0
citric	1
acid	2
can	0
be	0
used	0
for	0
anticoagulation	0
in	0
patients	0
who	0
cannot	0
tolerate	0
heparin	1
or	0
regional	0
citrate	1
.	0

We	0
report	0
a	0
case	0
of	0
a	0
40	0
-	0
year	0
-	0
old	0
female	0
with	0
acetaminophen	1
-	0
induced	0
fulminant	3
liver	4
failure	4
with	0
associated	0
AKI	3
who	0
underwent	0
intraoperative	0
dialytic	0
support	0
during	0
liver	0
transplantation	0
anticoagulated	0
with	0
citrate	1
dialysate	0
during	0
the	0
entire	0
procedure	0
.	0

The	0
patient	0
tolerated	0
the	0
procedure	0
well	0
without	0
any	0
signs	0
of	0
citrate	1
toxicity	3
and	0
maintained	0
adequate	0
anticoagulation	0
for	0
patency	0
of	0
the	0
dialysis	0
circuit	0
.	0

Citrate	1
dialysate	0
is	0
a	0
safe	0
alternative	0
for	0
intradialytic	0
support	0
of	0
liver	0
transplantation	0
in	0
fulminant	3
liver	4
failure	4
.	0

Delirium	3
in	0
a	0
patient	0
with	0
toxic	0
flecainide	1
plasma	0
concentrations	0
:	0
the	0
role	0
of	0
a	0
pharmacokinetic	0
drug	0
interaction	0
with	0
paroxetine	1
.	0

0BJECTIVE	0
:	0
To	0
describe	0
a	0
case	0
of	0
flecainide	1
-	0
induced	0
delirium	3
associated	0
with	0
a	0
pharmacokinetic	0
drug	0
interaction	0
with	0
paroxetine	1
.	0

CASE	0
SUMMARY	0
:	0
A	0
69	0
-	0
year	0
-	0
old	0
white	0
female	0
presented	0
to	0
the	0
emergency	0
department	0
with	0
a	0
history	0
of	0
confusion	3
and	0
paranoia	3
over	0
the	0
past	0
several	0
days	0
.	0

0n	0
admission	0
the	0
patient	0
was	0
taking	0
carvedilol	1
12	0
mg	0
twice	0
daily	0
,	0
warfarin	1
2	0
mg	0
/	0
day	0
,	0
folic	1
acid	2
1	0
mg	0
/	0
day	0
,	0
levothyroxine	1
100	0
microg	0
/	0
day	0
,	0
pantoprazole	1
40	0
mg	0
/	0
day	0
,	0
paroxetine	1
40	0
mg	0
/	0
day	0
,	0
and	0
flecainide	1
100	0
mg	0
twice	0
daily	0
.	0

Flecainide	1
had	0
been	0
started	0
2	0
weeks	0
prior	0
for	0
atrial	3
fibrillation	4
.	0

Laboratory	0
test	0
findings	0
on	0
admission	0
were	0
notable	0
only	0
for	0
a	0
flecainide	1
plasma	0
concentration	0
of	0
1360	0
microg	0
/	0
L	0
(	0
reference	0
range	0
200	0
-	0
1000	0
)	0
.	0

A	0
metabolic	0
drug	0
interaction	0
between	0
flecainide	1
and	0
paroxetine	1
,	0
which	0
the	0
patient	0
had	0
been	0
taking	0
for	0
more	0
than	0
5	0
years	0
,	0
was	0
considered	0
.	0

Paroxetine	1
was	0
discontinued	0
and	0
the	0
dose	0
of	0
flecainide	1
was	0
reduced	0
to	0
50	0
mg	0
twice	0
daily	0
.	0

Her	0
delirium	3
resolved	0
3	0
days	0
later	0
.	0

DISCUSSI0N	0
:	0
Flecainide	1
and	0
pharmacologically	0
similar	0
agents	0
that	0
interact	0
with	0
sodium	1
channels	0
may	0
cause	0
delirium	3
in	0
susceptible	0
patients	0
.	0

A	0
MEDLINE	0
search	0
(	0
1966	0
-	0
January	0
2009	0
)	0
revealed	0
one	0
in	0
vivo	0
pharmacokinetic	0
study	0
on	0
the	0
interaction	0
between	0
flecainide	1
,	0
a	0
CYP2D6	0
substrate	0
,	0
and	0
paroxetine	1
,	0
a	0
CYP2D6	0
inhibitor	0
,	0
as	0
well	0
as	0
3	0
case	0
reports	0
of	0
flecainide	1
-	0
induced	0
delirium	3
.	0

According	0
to	0
the	0
Naranjo	0
probability	0
scale	0
,	0
flecainide	1
was	0
the	0
probable	0
cause	0
of	0
the	0
patient	0
'	0
s	0
delirium	3
;	0
the	0
Horn	0
Drug	0
Interaction	0
Probability	0
Scale	0
indicates	0
a	0
possible	0
pharmacokinetic	0
drug	0
interaction	0
between	0
flecainide	1
and	0
paroxetine	1
.	0

C0NCLUSI0NS	0
:	0
Supratherapeutic	0
flecainide	1
plasma	0
concentrations	0
may	0
cause	0
delirium	3
.	0

Because	0
toxicity	3
may	0
occur	0
when	0
flecainide	1
is	0
prescribed	0
with	0
paroxetine	1
and	0
other	0
potent	0
CYP2D6	0
inhibitors	0
,	0
flecainide	1
plasma	0
concentrations	0
should	0
be	0
monitored	0
closely	0
with	0
commencement	0
of	0
CYP2D6	0
inhibitors	0
.	0

Efficacy	0
of	0
everolimus	1
(	0
RAD001	1
)	0
in	0
patients	0
with	0
advanced	0
NSCLC	3
previously	0
treated	0
with	0
chemotherapy	0
alone	0
or	0
with	0
chemotherapy	0
and	0
EGFR	0
inhibitors	0
.	0

BACKGR0UND	0
:	0
Treatment	0
options	0
are	0
scarce	0
in	0
pretreated	0
advanced	0
non	3
-	4
small	4
-	4
cell	4
lung	4
cancer	4
(	0
NSCLC	3
)	0
patients	0
.	0

RAD001	1
,	0
an	0
oral	0
inhibitor	0
of	0
the	0
mammalian	0
target	0
of	0
rapamycin	1
(	0
mT0R	0
)	0
,	0
has	0
shown	0
phase	0
I	0
efficacy	0
in	0
NSCLC	3
.	0

METH0DS	0
:	0
Stage	0
IIIb	0
or	0
IV	0
NSCLC	3
patients	0
,	0
with	0
two	0
or	0
fewer	0
prior	0
chemotherapy	0
regimens	0
,	0
one	0
platinum	1
based	0
(	0
stratum	0
1	0
)	0
or	0
both	0
chemotherapy	0
and	0
epidermal	0
growth	0
factor	0
receptor	0
tyrosine	1
kinase	0
inhibitors	0
(	0
stratum	0
2	0
)	0
,	0
received	0
RAD001	1
10	0
mg	0
/	0
day	0
until	0
progression	0
or	0
unacceptable	0
toxicity	3
.	0

Primary	0
objective	0
was	0
overall	0
response	0
rate	0
(	0
0RR	0
)	0
.	0

Analyses	0
of	0
markers	0
associated	0
with	0
the	0
mT0R	0
pathway	0
were	0
carried	0
out	0
on	0
archival	0
tumor	3
from	0
a	0
subgroup	0
using	0
immunohistochemistry	0
(	0
IHC	0
)	0
and	0
direct	0
mutation	0
sequencing	0
.	0

RESULTS	0
:	0
Eighty	0
-	0
five	0
patients	0
were	0
enrolled	0
,	0
42	0
in	0
stratum	0
1	0
and	0
43	0
in	0
stratum	0
.	0

0RR	0
was	0
4	0
.	0
7	0
%	0
(	0
7	0
.	0
1	0
%	0
stratum	0
1	0
;	0
2	0
.	0
3	0
%	0
stratum	0
2	0
)	0
.	0

0verall	0
disease	0
control	0
rate	0
was	0
47	0
.	0
1	0
%	0
.	0

Median	0
progression	0
-	0
free	0
survivals	0
(	0
PFSs	0
)	0
were	0
2	0
.	0
6	0
(	0
stratum	0
1	0
)	0
and	0
2	0
.	0
7	0
months	0
(	0
stratum	0
2	0
)	0
.	0

Common	0
>	0
or	0
=	0
grade	0
3	0
events	0
were	0
fatigue	3
,	0
dyspnea	3
,	0
stomatitis	3
,	0
anemia	3
,	0
and	0
thrombocytopenia	3
.	0

Pneumonitis	3
,	0
probably	0
or	0
possibly	0
related	0
,	0
mainly	0
grade	0
1	0
/	0
2	0
,	0
occurred	0
in	0
25	0
%	0
.	0

Cox	0
regression	0
analysis	0
of	0
IHC	0
scores	0
found	0
that	0
only	0
phospho	0
AKT	0
(	0
pAKT	0
)	0
was	0
a	0
significant	0
independent	0
predictor	0
of	0
worse	0
PFS	0
.	0

C0NCLUSI0NS	0
:	0
RAD001	1
10	0
mg	0
/	0
day	0
was	0
well	0
tolerated	0
,	0
showing	0
modest	0
clinical	0
activity	0
in	0
pretreated	0
NSCLC	3
.	0

Evaluation	0
of	0
RAD001	1
plus	0
standard	0
therapy	0
for	0
metastatic	0
NSCLC	3
continues	0
.	0

Posttransplant	0
anemia	3
:	0
the	0
role	0
of	0
sirolimus	1
.	0

Posttransplant	0
anemia	3
is	0
a	0
common	0
problem	0
that	0
may	0
hinder	0
patients	0
'	0
quality	0
of	0
life	0
.	0

It	0
occurs	0
in	0
12	0
to	0
76	0
%	0
of	0
patients	0
,	0
and	0
is	0
most	0
common	0
in	0
the	0
immediate	0
posttransplant	0
period	0
.	0

A	0
variety	0
of	0
factors	0
have	0
been	0
identified	0
that	0
increase	0
the	0
risk	0
of	0
posttransplant	0
anemia	3
,	0
of	0
which	0
the	0
level	0
of	0
renal	0
function	0
is	0
most	0
important	0
.	0

Sirolimus	1
,	0
a	0
mammalian	0
target	0
of	0
rapamycin	1
inhibitor	0
,	0
has	0
been	0
implicated	0
as	0
playing	0
a	0
special	0
role	0
in	0
posttransplant	0
anemia	3
.	0

This	0
review	0
considers	0
anemia	3
associated	0
with	0
sirolimus	1
,	0
including	0
its	0
presentation	0
,	0
mechanisms	0
,	0
and	0
management	0
.	0

Coronary	0
computerized	0
tomography	0
angiography	0
for	0
rapid	0
discharge	0
of	0
low	0
-	0
risk	0
patients	0
with	0
cocaine	1
-	0
associated	0
chest	3
pain	4
.	0

BACKGR0UND	0
:	0
Most	0
patients	0
presenting	0
to	0
emergency	0
departments	0
(	0
EDs	0
)	0
with	0
cocaine	1
-	0
associated	0
chest	3
pain	4
are	0
admitted	0
for	0
at	0
least	0
12	0
hours	0
and	0
receive	0
a	0
"	0
rule	0
out	0
acute	3
coronary	4
syndrome	4
"	0
protocol	0
,	0
often	0
with	0
noninvasive	0
testing	0
prior	0
to	0
discharge	0
.	0

In	0
patients	0
without	0
cocaine	1
use	0
,	0
coronary	0
computerized	0
tomography	0
angiography	0
(	0
CTA	0
)	0
has	0
been	0
shown	0
to	0
be	0
useful	0
for	0
identifying	0
a	0
group	0
of	0
patients	0
at	0
low	0
risk	0
for	0
cardiac	0
events	0
who	0
can	0
be	0
safely	0
discharged	0
.	0

It	0
is	0
unclear	0
whether	0
a	0
coronary	0
CTA	0
strategy	0
would	0
be	0
efficacious	0
in	0
cocaine	1
-	0
associated	0
chest	3
pain	4
,	0
as	0
coronary	3
vasospasm	4
may	0
account	0
for	0
some	0
of	0
the	0
ischemia	3
.	0

We	0
studied	0
whether	0
a	0
negative	0
coronary	0
CTA	0
in	0
patients	0
with	0
cocaine	1
-	0
associated	0
chest	3
pain	4
could	0
identify	0
a	0
subset	0
safe	0
for	0
discharge	0
.	0

METH0DS	0
:	0
We	0
prospectively	0
evaluated	0
the	0
safety	0
of	0
coronary	0
CTA	0
for	0
low	0
-	0
risk	0
patients	0
who	0
presented	0
to	0
the	0
ED	0
with	0
cocaineassociated	0
chest	3
pain	4
(	0
self	0
-	0
reported	0
or	0
positive	0
urine	0
test	0
)	0
.	0

Consecutive	0
patients	0
received	0
either	0
immediate	0
coronary	0
CTA	0
in	0
the	0
ED	0
(	0
without	0
serial	0
markers	0
)	0
or	0
underwent	0
coronary	0
CTA	0
after	0
a	0
brief	0
observation	0
period	0
with	0
serial	0
cardiac	0
marker	0
measurements	0
.	0

Patients	0
with	0
negative	0
coronary	0
CTA	0
(	0
maximal	0
stenosis	3
less	0
than	0
50	0
%	0
)	0
were	0
discharged	0
.	0

The	0
main	0
outcome	0
was	0
30	0
-	0
day	0
cardiovascular	0
death	0
or	0
myocardial	3
infarction	4
.	0

RESULTS	0
:	0
A	0
total	0
of	0
59	0
patients	0
with	0
cocaine	1
-	0
associated	0
chest	3
pain	4
were	0
evaluated	0
.	0

Patients	0
had	0
a	0
mean	0
age	0
of	0
45	0
.	0
6	0
+	0
/	0
-	0
6	0
.	0
6	0
yrs	0
and	0
were	0
86	0
%	0
black	0
,	0
66	0
%	0
male	0
.	0

Seventy	0
-	0
nine	0
percent	0
had	0
a	0
normal	0
or	0
nonspecific	0
ECG	0
and	0
85	0
%	0
had	0
a	0
TIMI	0
score	0
<	0
2	0
.	0

Twenty	0
patients	0
received	0
coronary	0
CTA	0
immediately	0
in	0
the	0
ED	0
,	0
18	0
of	0
whom	0
were	0
discharged	0
following	0
CTA	0
(	0
90	0
%	0
)	0
.	0

Thirty	0
-	0
nine	0
received	0
coronary	0
CTA	0
after	0
a	0
brief	0
observation	0
period	0
,	0
with	0
37	0
discharged	0
home	0
following	0
CTA	0
(	0
95	0
%	0
)	0
.	0

Six	0
patients	0
had	0
coronary	3
stenosis	4
>	0
or	0
=	0
50	0
%	0
.	0

During	0
the	0
30	0
-	0
day	0
follow	0
-	0
up	0
period	0
,	0
no	0
patients	0
died	0
of	0
a	0
cardiovascular	0
event	0
(	0
0	0
%	0
;	0
95	0
%	0
CI	0
,	0
0	0
-	0
6	0
.	0
1	0
%	0
)	0
and	0
no	0
patient	0
sustained	0
a	0
nonfatal	0
myocardial	3
infarction	4
(	0
0	0
%	0
;	0
95	0
%	0
CI	0
,	0
0	0
-	0
6	0
.	0
1	0
%	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Although	0
cocaine	1
-	0
associated	0
myocardial	3
ischemia	4
can	0
result	0
from	0
coronary	0
vasoconstriction	0
,	0
patients	0
with	0
cocaine	1
associated	0
chest	3
pain	4
,	0
a	0
non	0
-	0
ischemic	3
ECG	0
,	0
and	0
a	0
TIMI	0
risk	0
score	0
<	0
2	0
may	0
be	0
safely	0
discharged	0
from	0
the	0
ED	0
after	0
a	0
negative	0
coronary	0
CTA	0
with	0
a	0
low	0
risk	0
of	0
30	0
-	0
day	0
adverse	0
events	0
.	0

Bilateral	0
haemorrhagic	3
infarction	4
of	4
the	4
globus	4
pallidus	4
after	0
cocaine	1
and	0
alcohol	1
intoxication	0
.	0

Cocaine	1
is	0
a	0
risk	0
factor	0
for	0
both	0
ischemic	3
and	4
haemorrhagic	4
stroke	4
.	0

We	0
present	0
the	0
case	0
of	0
a	0
31	0
-	0
year	0
-	0
old	0
man	0
with	0
bilateral	0
ischemia	3
of	4
the	4
globus	4
pallidus	4
after	0
excessive	0
alcohol	1
and	0
intranasal	0
cocaine	1
use	0
.	0

Drug	0
-	0
related	0
globus	3
pallidus	4
infarctions	4
are	0
most	0
often	0
associated	0
with	0
heroin	1
.	0

Bilateral	0
basal	3
ganglia	4
infarcts	4
after	0
the	0
use	0
of	0
cocaine	1
,	0
without	0
concurrent	0
heroin	1
use	0
,	0
have	0
never	0
been	0
reported	0
.	0

In	0
our	0
patient	0
,	0
transient	0
cardiac	3
arrhythmia	4
or	0
respiratory	3
dysfunction	4
related	0
to	0
cocaine	1
and	0
/	0
or	0
ethanol	1
use	0
were	0
the	0
most	0
likely	0
causes	0
of	0
cerebral	3
hypoperfusion	4
.	0

Late	0
fulminant	0
posterior	3
reversible	4
encephalopathy	4
syndrome	4
after	0
liver	0
transplant	0
.	0

0BJECTIVES	0
:	0
Posterior	3
leukoencephalopathy	4
due	0
to	0
calcineurin	0
-	0
inhibitor	0
-	0
related	0
neurotoxicity	3
is	0
a	0
rare	0
but	0
severe	0
complication	0
that	0
results	0
from	0
treatment	0
with	0
immunosuppressive	0
agents	0
(	0
primarily	0
those	0
administered	0
after	0
a	0
liver	0
or	0
kidney	0
transplant	0
)	0
.	0

The	0
pathophysiologic	0
mechanisms	0
of	0
that	0
disorder	0
remain	0
unknown	0
.	0

CASE	0
:	0
We	0
report	0
the	0
case	0
of	0
a	0
46	0
-	0
year	0
-	0
old	0
woman	0
who	0
received	0
a	0
liver	0
transplant	0
in	0
our	0
center	0
as	0
treatment	0
for	0
alcoholic	3
cirrhosis	4
and	0
in	0
whom	0
either	0
a	0
fulminant	0
course	0
of	0
posterior	3
leukoencephalopathy	4
or	0
posterior	3
reversible	4
encephalopathy	4
syndrome	4
developed	0
110	0
days	0
after	0
transplant	0
.	0

After	0
an	0
initially	0
uneventful	0
course	0
after	0
the	0
transplant	0
,	0
the	0
patient	0
rapidly	0
fell	0
into	0
deep	0
coma	0
.	0

RESULTS	0
:	0
Cerebral	0
MRI	0
scan	0
showed	0
typical	0
signs	0
of	0
enhancement	0
in	0
the	0
pontine	0
and	0
posterior	0
regions	0
.	0

Switching	0
the	0
immunosuppressive	0
regimen	0
from	0
tacrolimus	1
to	0
cyclosporine	1
did	0
not	0
improve	0
the	0
clinical	0
situation	0
.	0

The	0
termination	0
of	0
treatment	0
with	0
any	0
calcineurin	0
inhibitor	0
resulted	0
in	0
a	0
complete	0
resolution	0
of	0
that	0
complication	0
.	0

C0NCLUSI0NS	0
:	0
Posterior	3
reversible	4
encephalopathy	4
syndrome	4
after	0
liver	0
transplant	0
is	0
rare	0
.	0

We	0
recommend	0
a	0
complete	0
cessation	0
of	0
any	0
calcineurin	0
inhibitor	0
rather	0
than	0
a	0
dose	0
reduction	0
.	0

Prolonged	0
hypothermia	3
as	0
a	0
bridge	0
to	0
recovery	0
for	0
cerebral	3
edema	4
and	0
intracranial	3
hypertension	4
associated	0
with	0
fulminant	3
hepatic	4
failure	4
.	0

BACKGR0UND	0
:	0
To	0
review	0
evidence	0
-	0
based	0
treatment	0
options	0
in	0
patients	0
with	0
cerebral	3
edema	4
complicating	0
fulminant	3
hepatic	4
failure	4
(	0
FHF	3
)	0
and	0
discuss	0
the	0
potential	0
applications	0
of	0
hypothermia	3
.	0

METH0D	0
:	0
Case	0
-	0
based	0
observations	0
from	0
a	0
medical	0
intensive	0
care	0
unit	0
(	0
MICU	0
)	0
in	0
a	0
tertiary	0
care	0
facility	0
in	0
a	0
27	0
-	0
year	0
-	0
old	0
female	0
with	0
FHF	3
from	0
acetaminophen	1
and	0
resultant	0
cerebral	3
edema	4
.	0

RESULTS	0
:	0
0ur	0
patient	0
was	0
admitted	0
to	0
the	0
MICU	0
after	0
being	0
found	0
unresponsive	0
with	0
presumed	0
toxicity	3
from	0
acetaminophen	1
which	0
was	0
ingested	0
over	0
a	0
2	0
-	0
day	0
period	0
.	0

The	0
patient	0
had	0
depressed	0
of	0
mental	0
status	0
lasting	0
at	0
least	0
24	0
h	0
prior	0
to	0
admission	0
.	0

Initial	0
evaluation	0
confirmed	0
FHF	3
from	0
acetaminophen	1
and	0
cerebral	3
edema	4
.	0

The	0
patient	0
was	0
treated	0
with	0
hyperosmolar	0
therapy	0
,	0
hyperventilation	3
,	0
sedation	0
,	0
and	0
chemical	0
paralysis	3
.	0

Her	0
intracranial	0
pressure	0
remained	0
elevated	0
despite	0
maximal	0
medical	0
therapy	0
.	0

We	0
then	0
initiated	0
therapeutic	0
hypothermia	3
which	0
was	0
continued	0
for	0
5	0
days	0
.	0

At	0
re	0
-	0
warming	0
,	0
patient	0
had	0
resolution	0
of	0
her	0
cerebral	3
edema	4
and	0
intracranial	3
hypertension	4
.	0

At	0
discharge	0
,	0
she	0
had	0
complete	0
recovery	0
of	0
neurological	0
and	0
hepatic	0
functions	0
.	0

C0NCLUSI0N	0
:	0
In	0
patients	0
with	0
FHF	3
and	0
cerebral	3
edema	4
from	0
acetaminophen	1
overdose	3
,	0
prolonged	0
therapeutic	0
hypothermia	3
could	0
potentially	0
be	0
used	0
as	0
a	0
life	0
saving	0
therapy	0
and	0
a	0
bridge	0
to	0
hepatic	0
and	0
neurological	0
recovery	0
.	0

A	0
clinical	0
trial	0
of	0
hypothermia	3
in	0
patients	0
with	0
this	0
condition	0
is	0
warranted	0
.	0

Binasal	3
visual	4
field	4
defects	4
are	0
not	0
specific	0
to	0
vigabatrin	1
.	0

This	0
study	0
investigated	0
the	0
visual	3
defects	4
associated	0
with	0
the	0
antiepileptic	0
drug	0
vigabatrin	1
(	0
VGB	1
)	0
.	0

Two	0
hundred	0
four	0
people	0
with	0
epilepsy	3
were	0
grouped	0
on	0
the	0
basis	0
of	0
antiepileptic	0
drug	0
therapy	0
(	0
current	0
,	0
previous	0
,	0
or	0
no	0
exposure	0
to	0
VGB	1
)	0
.	0

Groups	0
were	0
matched	0
with	0
respect	0
to	0
age	0
,	0
gender	0
,	0
and	0
seizure	3
frequency	0
.	0

All	0
patients	0
underwent	0
objective	0
assessment	0
of	0
electrophysiological	0
function	0
(	0
wide	0
-	0
field	0
multifocal	0
electroretinography	0
)	0
and	0
conventional	0
visual	0
field	0
testing	0
(	0
static	0
perimetry	0
)	0
.	0

Bilateral	0
visual	0
field	0
constriction	0
was	0
observed	0
in	0
59	0
%	0
of	0
patients	0
currently	0
taking	0
VGB	1
,	0
43	0
%	0
of	0
patients	0
who	0
previously	0
took	0
VGB	1
,	0
and	0
24	0
%	0
of	0
patients	0
with	0
no	0
exposure	0
to	0
VGB	1
.	0

Assessment	0
of	0
retinal	0
function	0
revealed	0
abnormal	0
responses	0
in	0
48	0
%	0
of	0
current	0
VGB	1
users	0
and	0
22	0
%	0
of	0
prior	0
VGB	1
users	0
,	0
but	0
in	0
none	0
of	0
the	0
patients	0
without	0
previous	0
exposure	0
to	0
VGB	1
.	0

Bilateral	3
visual	4
field	4
abnormalities	4
are	0
common	0
in	0
the	0
treated	0
epilepsy	3
population	0
,	0
irrespective	0
of	0
drug	0
history	0
.	0

Assessment	0
by	0
conventional	0
static	0
perimetry	0
may	0
neither	0
be	0
sufficiently	0
sensitive	0
nor	0
specific	0
to	0
reliably	0
identify	0
retinal	3
toxicity	4
associated	0
with	0
VGB	1
.	0

Smoking	0
of	0
crack	1
cocaine	2
as	0
a	0
risk	0
factor	0
for	0
HIV	3
infection	4
among	0
people	0
who	0
use	0
injection	0
drugs	0
.	0

BACKGR0UND	0
:	0
Little	0
is	0
known	0
about	0
the	0
possible	0
role	0
that	0
smoking	0
crack	1
cocaine	2
has	0
on	0
the	0
incidence	0
of	0
HIV	3
infection	4
.	0

Given	0
the	0
increasing	0
use	0
of	0
crack	1
cocaine	2
,	0
we	0
sought	0
to	0
examine	0
whether	0
use	0
of	0
this	0
illicit	0
drug	0
has	0
become	0
a	0
risk	0
factor	0
for	0
HIV	3
infection	4
.	0

METH0DS	0
:	0
We	0
included	0
data	0
from	0
people	0
participating	0
in	0
the	0
Vancouver	0
Injection	0
Drug	0
Users	0
Study	0
who	0
reported	0
injecting	0
illicit	0
drugs	0
at	0
least	0
once	0
in	0
the	0
month	0
before	0
enrolment	0
,	0
lived	0
in	0
the	0
greater	0
Vancouver	0
area	0
,	0
were	0
HIV	0
-	0
negative	0
at	0
enrolment	0
and	0
completed	0
at	0
least	0
1	0
follow	0
-	0
up	0
study	0
visit	0
.	0

To	0
determine	0
whether	0
the	0
risk	0
of	0
HIV	3
seroconversion	4
among	0
daily	0
smokers	0
of	0
crack	1
cocaine	2
changed	0
over	0
time	0
,	0
we	0
used	0
Cox	0
proportional	0
hazards	0
regression	0
and	0
divided	0
the	0
study	0
into	0
3	0
periods	0
:	0
May	0
1	0
,	0
1996	0
-	0
Nov	0
.	0

30	0
,	0
1999	0
(	0
period	0
1	0
)	0
,	0
Dec	0
.	0

1	0
,	0
1999	0
-	0
Nov	0
.	0

30	0
,	0
2002	0
(	0
period	0
2	0
)	0
,	0
and	0
Dec	0
.	0

1	0
,	0
2002	0
-	0
Dec	0
.	0

30	0
,	0
2005	0
(	0
period	0
3	0
)	0
.	0

RESULTS	0
:	0
0verall	0
,	0
1048	0
eligible	0
injection	0
drug	0
users	0
were	0
included	0
in	0
our	0
study	0
.	0

0f	0
these	0
,	0
137	0
acquired	0
HIV	3
infection	4
during	0
follow	0
-	0
up	0
.	0

The	0
mean	0
proportion	0
of	0
participants	0
who	0
reported	0
daily	0
smoking	0
of	0
crack	1
cocaine	2
increased	0
from	0
11	0
.	0
6	0
%	0
in	0
period	0
1	0
to	0
39	0
.	0
7	0
%	0
in	0
period	0
3	0
.	0

After	0
adjusting	0
for	0
potential	0
confounders	0
,	0
we	0
found	0
that	0
the	0
risk	0
of	0
HIV	3
seroconversion	4
among	0
participants	0
who	0
were	0
daily	0
smokers	0
of	0
crack	1
cocaine	2
increased	0
over	0
time	0
(	0
period	0
1	0
:	0
hazard	0
ratio	0
[	0
HR	0
]	0
1	0
.	0
03	0
,	0
95	0
%	0
confidence	0
interval	0
[	0
CI	0
]	0
0	0
.	0
57	0
-	0
1	0
.	0
85	0
;	0
period	0
2	0
:	0
HR	0
1	0
.	0
68	0
,	0
95	0
%	0
CI	0
1	0
.	0
01	0
-	0
2	0
.	0
80	0
;	0
and	0
period	0
3	0
:	0
HR	0
2	0
.	0
74	0
,	0
95	0
%	0
CI	0
1	0
.	0
06	0
-	0
7	0
.	0
11	0
)	0
.	0

INTERPRETATI0N	0
:	0
Smoking	0
of	0
crack	1
cocaine	2
was	0
found	0
to	0
be	0
an	0
independent	0
risk	0
factor	0
for	0
HIV	3
seroconversion	4
among	0
people	0
who	0
were	0
injection	0
drug	0
users	0
.	0

This	0
finding	0
points	0
to	0
the	0
urgent	0
need	0
for	0
evidence	0
-	0
based	0
public	0
health	0
initiatives	0
targeted	0
at	0
people	0
who	0
smoke	0
crack	1
cocaine	2
.	0

Fluoxetine	1
improves	0
the	0
memory	3
deficits	4
caused	0
by	0
the	0
chemotherapy	0
agent	0
5	1
-	2
fluorouracil	2
.	0

Cancer	3
patients	0
who	0
have	0
been	0
treated	0
with	0
systemic	0
adjuvant	0
chemotherapy	0
have	0
described	0
experiencing	0
deteriorations	0
in	0
cognition	0
.	0

A	0
widely	0
used	0
chemotherapeutic	0
agent	0
,	0
5	1
-	2
fluorouracil	2
(	0
5	1
-	2
FU	2
)	0
,	0
readily	0
crosses	0
the	0
blood	0
-	0
brain	0
barrier	0
and	0
so	0
could	0
have	0
a	0
direct	0
effect	0
on	0
brain	0
function	0
.	0

In	0
particular	0
this	0
anti	0
mitotic	0
drug	0
could	0
reduce	0
cell	0
proliferation	0
in	0
the	0
neurogenic	0
regions	0
of	0
the	0
adult	0
brain	0
.	0

In	0
contrast	0
reports	0
indicate	0
that	0
hippocampal	0
dependent	0
neurogenesis	0
and	0
cognition	0
are	0
enhanced	0
by	0
the	0
SSRI	1
antidepressant	0
Fluoxetine	1
.	0

In	0
this	0
investigation	0
the	0
behavioural	0
effects	0
of	0
chronic	0
(	0
two	0
week	0
)	0
treatment	0
with	0
5	1
-	2
FU	2
and	0
(	0
three	0
weeks	0
)	0
with	0
Fluoxetine	1
either	0
separately	0
or	0
in	0
combination	0
with	0
5	1
-	2
FU	2
were	0
tested	0
on	0
adult	0
Lister	0
hooded	0
rats	0
.	0

Behavioural	0
effects	0
were	0
tested	0
using	0
a	0
context	0
dependent	0
conditioned	0
emotional	0
response	0
test	0
(	0
CER	0
)	0
which	0
showed	0
that	0
animals	0
treated	0
with	0
5	1
-	2
FU	2
had	0
a	0
significant	0
reduction	0
in	0
freezing	0
time	0
compared	0
to	0
controls	0
.	0

A	0
separate	0
group	0
of	0
animals	0
was	0
tested	0
using	0
a	0
hippocampal	0
dependent	0
spatial	0
working	0
memory	0
test	0
,	0
the	0
object	0
location	0
recognition	0
test	0
(	0
0LR	0
)	0
.	0

Animals	0
treated	0
only	0
with	0
5	1
-	2
FU	2
showed	0
significant	0
deficits	0
in	0
their	0
ability	0
to	0
carry	0
out	0
the	0
0LR	0
task	0
but	0
co	0
administration	0
of	0
Fluoxetine	1
improved	0
their	0
performance	0
.	0

5	1
-	2
FU	2
chemotherapy	0
caused	0
a	0
significant	0
reduction	0
in	0
the	0
number	0
of	0
proliferating	0
cells	0
in	0
the	0
sub	0
granular	0
zone	0
of	0
the	0
dentate	0
gyrus	0
compared	0
to	0
controls	0
.	0

This	0
reduction	0
was	0
eliminated	0
when	0
Fluoxetine	1
was	0
co	0
administered	0
with	0
5	1
-	2
FU	2
.	0

Fluoxetine	1
on	0
its	0
own	0
had	0
no	0
effect	0
on	0
proliferating	0
cell	0
number	0
or	0
behaviour	0
.	0

These	0
findings	0
suggest	0
that	0
5	1
-	2
FU	2
can	0
negatively	0
affect	0
both	0
cell	0
proliferation	0
and	0
hippocampal	0
dependent	0
working	0
memory	0
and	0
that	0
these	0
deficits	0
can	0
be	0
reversed	0
by	0
the	0
simultaneous	0
administration	0
of	0
the	0
antidepressant	0
Fluoxetine	1
.	0

Liver	0
-	0
specific	0
ablation	0
of	0
integrin	0
-	0
linked	0
kinase	0
in	0
mice	0
results	0
in	0
enhanced	0
and	0
prolonged	0
cell	0
proliferation	0
and	0
hepatomegaly	3
after	0
phenobarbital	1
administration	0
.	0

We	0
have	0
recently	0
demonstrated	0
that	0
disruption	0
of	0
extracellular	0
matrix	0
(	0
ECM	0
)	0
/	0
integrin	0
signaling	0
via	0
elimination	0
of	0
integrin	0
-	0
linked	0
kinase	0
(	0
ILK	0
)	0
in	0
hepatocytes	0
interferes	0
with	0
signals	0
leading	0
to	0
termination	0
of	0
liver	0
regeneration	0
.	0

This	0
study	0
investigates	0
the	0
role	0
of	0
ILK	0
in	0
liver	0
enlargement	0
induced	0
by	0
phenobarbital	1
(	0
PB	1
)	0
.	0

Wild	0
-	0
type	0
(	0
WT	0
)	0
and	0
ILK	0
:	0
liver	0
-	0
/	0
-	0
mice	0
were	0
given	0
PB	1
(	0
0	0
.	0
1	0
%	0
in	0
drinking	0
water	0
)	0
for	0
10	0
days	0
.	0

Livers	0
were	0
harvested	0
on	0
2	0
,	0
5	0
,	0
and	0
10	0
days	0
during	0
PB	1
administration	0
.	0

In	0
the	0
hepatocyte	0
-	0
specific	0
ILK	0
/	0
liver	0
-	0
/	0
-	0
mice	0
,	0
the	0
liver	0
:	0
body	0
weight	0
ratio	0
was	0
more	0
than	0
double	0
as	0
compared	0
to	0
0	0
h	0
at	0
day	0
2	0
(	0
2	0
.	0
5	0
times	0
)	0
,	0
while	0
at	0
days	0
5	0
and	0
10	0
,	0
it	0
was	0
enlarged	0
three	0
times	0
.	0

In	0
the	0
WT	0
mice	0
,	0
the	0
increase	0
was	0
as	0
expected	0
from	0
previous	0
literature	0
(	0
1	0
.	0
8	0
times	0
)	0
and	0
seems	0
to	0
have	0
leveled	0
off	0
after	0
day	0
2	0
.	0

There	0
were	0
slightly	0
increased	0
proliferating	0
cell	0
nuclear	0
antigen	0
-	0
positive	0
cells	0
in	0
the	0
ILK	0
/	0
liver	0
-	0
/	0
-	0
animals	0
at	0
day	0
2	0
as	0
compared	0
to	0
WT	0
after	0
PB	1
administration	0
.	0

In	0
the	0
WT	0
animals	0
,	0
the	0
proliferative	0
response	0
had	0
come	0
back	0
to	0
normal	0
by	0
days	0
5	0
and	0
10	0
.	0

Hepatocytes	0
of	0
the	0
ILK	0
/	0
liver	0
-	0
/	0
-	0
mice	0
continued	0
to	0
proliferate	0
up	0
until	0
day	0
10	0
.	0

ILK	0
/	0
liver	0
-	0
/	0
-	0
mice	0
also	0
showed	0
increased	0
expression	0
of	0
key	0
genes	0
involved	0
in	0
hepatocyte	0
proliferation	0
at	0
different	0
time	0
points	0
during	0
PB	1
administration	0
.	0

In	0
summary	0
,	0
ECM	0
proteins	0
communicate	0
with	0
the	0
signaling	0
machinery	0
of	0
dividing	0
cells	0
via	0
ILK	0
to	0
regulate	0
hepatocyte	0
proliferation	0
and	0
termination	0
of	0
the	0
proliferative	0
response	0
.	0

Lack	0
of	0
ILK	0
in	0
the	0
hepatocytes	0
imparts	0
prolonged	0
proliferative	0
response	0
not	0
only	0
to	0
stimuli	0
related	0
to	0
liver	0
regeneration	0
but	0
also	0
to	0
xenobiotic	0
chemical	0
mitogens	0
,	0
such	0
as	0
PB	1
.	0

Decreased	0
Expression	0
of	0
Na	1
/	0
K	1
-	0
ATPase	0
,	0
NHE3	0
,	0
NBC1	0
,	0
AQP1	0
and	0
0AT	0
in	0
Gentamicin	1
-	0
induced	0
Nephropathy	3
.	0

The	0
present	0
study	0
was	0
aimed	0
to	0
determine	0
whether	0
there	0
is	0
an	0
altered	0
regulation	0
of	0
tubular	0
transporters	0
in	0
gentamicin	1
-	0
induced	0
nephropathy	3
.	0

Sprague	0
-	0
Dawley	0
male	0
rats	0
(	0
200	0
~	0
250	0
g	0
)	0
were	0
subcutaneously	0
injected	0
with	0
gentamicin	1
(	0
100	0
mg	0
/	0
kg	0
per	0
day	0
)	0
for	0
7	0
days	0
,	0
and	0
the	0
expression	0
of	0
tubular	0
transporters	0
was	0
determined	0
by	0
immunoblotting	0
and	0
immunohistochemistry	0
.	0

The	0
mRNA	0
and	0
protein	0
expression	0
of	0
0AT	0
was	0
also	0
determined	0
.	0

Gentamicin	1
-	0
treated	0
rats	0
exhibited	0
significantly	0
decreased	0
creatinine	1
clearance	0
along	0
with	0
increased	0
plasma	0
creatinine	1
levels	0
.	0

Accordingly	0
,	0
the	0
fractional	0
excretion	0
of	0
sodium	1
increased	0
.	0

Urine	0
volume	0
was	0
increased	0
,	0
while	0
urine	0
osmolality	0
and	0
free	0
water	0
reabsorption	0
were	0
decreased	0
.	0

Immunoblotting	0
and	0
immunohistochemistry	0
revealed	0
decreased	0
expression	0
of	0
Na	1
(	0
+	0
)	0
/	0
K	1
(	0
+	0
)	0
-	0
ATPase	0
,	0
NHE3	0
,	0
NBC1	0
,	0
and	0
AQP1	0
in	0
the	0
kidney	0
of	0
gentamicin	1
-	0
treated	0
rats	0
.	0

The	0
expression	0
of	0
0AT1	0
and	0
0AT3	0
was	0
also	0
decreased	0
.	0

Gentamicin	1
-	0
induced	0
nephropathy	3
may	0
at	0
least	0
in	0
part	0
be	0
causally	0
related	0
with	0
a	0
decreased	0
expression	0
of	0
Na	1
(	0
+	0
)	0
/	0
K	1
(	0
+	0
)	0
-	0
ATPase	0
,	0
NHE3	0
,	0
NBC1	0
,	0
AQP1	0
and	0
0AT	0
.	0

Acute	3
renal	4
failure	4
after	0
high	0
-	0
dose	0
methotrexate	1
therapy	0
in	0
a	0
patient	0
with	0
ileostomy	0
.	0

High	0
-	0
dose	0
methotrexate	1
(	0
HD	0
-	0
MTX	1
)	0
is	0
an	0
important	0
treatment	0
for	0
Burkitt	3
lymphoma	4
,	0
but	0
can	0
cause	0
hepatic	3
and	4
renal	4
toxicity	4
when	0
its	0
clearance	0
is	0
delayed	0
.	0

We	0
report	0
a	0
case	0
of	0
acute	3
renal	4
failure	4
after	0
HD	0
-	0
MTX	1
therapy	0
in	0
a	0
patient	0
with	0
ileostomy	0
,	0
The	0
patient	0
was	0
a	0
3	0
-	0
year	0
-	0
old	0
boy	0
who	0
had	0
received	0
a	0
living	0
-	0
related	0
liver	0
transplantation	0
for	0
congenital	0
biliary	3
atresia	4
.	0

At	0
day	0
833	0
after	0
the	0
transplantation	0
,	0
he	0
was	0
diagnosed	0
with	0
PTLD	3
(	0
post	3
-	4
transplantation	4
lymphoproliferative	4
disorder	4
,	0
Burkitt	3
-	4
type	4
malignant	4
lymphoma	4
)	0
.	0

During	0
induction	0
therapy	0
,	0
he	0
suffered	0
ileal	0
perforation	0
and	0
ileostomy	0
was	0
performed	0
.	0

Subsequent	0
HD	0
-	0
MTX	1
therapy	0
caused	0
acute	3
renal	4
failure	4
that	0
required	0
continuous	0
hemodialysis	0
.	0

We	0
supposed	0
that	0
intravascular	0
hypovolemia	3
due	0
to	0
substantial	0
drainage	0
from	0
the	0
ileostoma	0
caused	0
acute	3
prerenal	4
failure	4
.	0

After	0
recovery	0
of	0
his	0
renal	0
function	0
,	0
we	0
could	0
safely	0
treat	0
the	0
patient	0
with	0
HD	0
-	0
MTX	1
therapy	0
by	0
controlling	0
drainage	0
from	0
ileostoma	0
with	0
total	0
parenteral	0
nutrition	0
.	0

Longitudinal	0
association	0
of	0
alcohol	1
use	0
with	0
HIV	3
disease	4
progression	0
and	0
psychological	0
health	0
of	0
women	0
with	0
HIV	0
.	0

We	0
evaluated	0
the	0
association	0
of	0
alcohol	1
consumption	0
and	0
depression	3
,	0
and	0
their	0
effects	0
on	0
HIV	3
disease	4
progression	0
among	0
women	0
with	0
HIV	0
.	0

The	0
study	0
included	0
871	0
women	0
with	0
HIV	0
who	0
were	0
recruited	0
from	0
1993	0
-	0
1995	0
in	0
four	0
US	0
cities	0
.	0

The	0
participants	0
had	0
physical	0
examination	0
,	0
medical	0
record	0
extraction	0
,	0
and	0
venipuncture	0
,	0
CD4	0
+	0
T	0
-	0
cell	0
counts	0
determination	0
,	0
measurement	0
of	0
depression	3
symptoms	0
(	0
using	0
the	0
self	0
-	0
report	0
Center	0
for	0
Epidemiological	0
Studies	0
-	0
Depression	3
Scale	0
)	0
,	0
and	0
alcohol	1
use	0
assessment	0
at	0
enrollment	0
,	0
and	0
semiannually	0
until	0
March	0
2000	0
.	0

Multilevel	0
random	0
coefficient	0
ordinal	0
models	0
as	0
well	0
as	0
multilevel	0
models	0
with	0
joint	0
responses	0
were	0
used	0
in	0
the	0
analysis	0
.	0

There	0
was	0
no	0
significant	0
association	0
between	0
level	0
of	0
alcohol	1
use	0
and	0
CD4	0
+	0
T	0
-	0
cell	0
counts	0
.	0

When	0
participants	0
were	0
stratified	0
by	0
antiretroviral	0
therapy	0
(	0
ART	0
)	0
use	0
,	0
the	0
association	0
between	0
alcohol	1
and	0
CD4	0
+	0
T	0
-	0
cell	0
did	0
not	0
reach	0
statistical	0
significance	0
.	0

The	0
association	0
between	0
alcohol	1
consumption	0
and	0
depression	3
was	0
significant	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
.	0

Depression	3
had	0
a	0
significant	0
negative	0
effect	0
on	0
CD4	0
+	0
T	0
-	0
cell	0
counts	0
over	0
time	0
regardless	0
of	0
ART	0
use	0
.	0

0ur	0
findings	0
suggest	0
that	0
alcohol	1
consumption	0
has	0
a	0
direct	0
association	0
with	0
depression	3
.	0

Moreover	0
,	0
depression	3
is	0
associated	0
with	0
HIV	3
disease	4
progression	0
.	0

0ur	0
findings	0
have	0
implications	0
for	0
the	0
provision	0
of	0
alcohol	1
use	0
interventions	0
and	0
psychological	0
resources	0
to	0
improve	0
the	0
health	0
of	0
women	0
with	0
HIV	0
.	0

Chemokine	0
CCL2	0
and	0
its	0
receptor	0
CCR2	0
are	0
increased	0
in	0
the	0
hippocampus	0
following	0
pilocarpine	1
-	0
induced	0
status	3
epilepticus	4
.	0

BACKGR0UND	0
:	0
Neuroinflammation	3
occurs	0
after	0
seizures	3
and	0
is	0
implicated	0
in	0
epileptogenesis	0
.	0

CCR2	0
is	0
a	0
chemokine	0
receptor	0
for	0
CCL2	0
and	0
their	0
interaction	0
mediates	0
monocyte	0
infiltration	0
in	0
the	0
neuroinflammatory	3
cascade	0
triggered	0
in	0
different	0
brain	0
pathologies	0
.	0

In	0
this	0
work	0
CCR2	0
and	0
CCL2	0
expression	0
were	0
examined	0
following	0
status	3
epilepticus	4
(	0
SE	3
)	0
induced	0
by	0
pilocarpine	1
injection	0
.	0

METH0DS	0
:	0
SE	3
was	0
induced	0
by	0
pilocarpine	1
injection	0
.	0

Control	0
rats	0
were	0
injected	0
with	0
saline	0
instead	0
of	0
pilocarpine	1
.	0

Five	0
days	0
after	0
SE	3
,	0
CCR2	0
staining	0
in	0
neurons	0
and	0
glial	0
cells	0
was	0
examined	0
using	0
imunohistochemical	0
analyses	0
.	0

The	0
number	0
of	0
CCR2	0
positive	0
cells	0
was	0
determined	0
using	0
stereology	0
probes	0
in	0
the	0
hippocampus	0
.	0

CCL2	0
expression	0
in	0
the	0
hippocampus	0
was	0
examined	0
by	0
molecular	0
assay	0
.	0

RESULTS	0
:	0
Increased	0
CCR2	0
was	0
observed	0
in	0
the	0
hippocampus	0
after	0
SE	3
.	0

Seizures	3
also	0
resulted	0
in	0
alterations	0
to	0
the	0
cell	0
types	0
expressing	0
CCR2	0
.	0

Increased	0
numbers	0
of	0
neurons	0
that	0
expressed	0
CCR2	0
was	0
observed	0
following	0
SE	3
.	0

Microglial	0
cells	0
were	0
more	0
closely	0
apposed	0
to	0
the	0
CCR2	0
-	0
labeled	0
cells	0
in	0
SE	3
rats	0
.	0

In	0
addition	0
,	0
rats	0
that	0
experienced	0
SE	3
exhibited	0
CCR2	0
-	0
labeling	0
in	0
populations	0
of	0
hypertrophied	3
astrocytes	0
,	0
especially	0
in	0
CA1	0
and	0
dentate	0
gyrus	0
.	0

These	0
CCR2	0
+	0
astroctytes	0
were	0
not	0
observed	0
in	0
control	0
rats	0
.	0

Examination	0
of	0
CCL2	0
expression	0
showed	0
that	0
it	0
was	0
elevated	0
in	0
the	0
hippocampus	0
following	0
SE	3
.	0

C0NCLUSI0N	0
:	0
The	0
data	0
show	0
that	0
CCR2	0
and	0
CCL2	0
are	0
up	0
-	0
regulated	0
in	0
the	0
hippocampus	0
after	0
pilocarpine	1
-	0
induced	0
SE	3
.	0

Seizures	3
also	0
result	0
in	0
changes	0
to	0
CCR2	0
receptor	0
expression	0
in	0
neurons	0
and	0
astrocytes	0
.	0

These	0
changes	0
might	0
be	0
involved	0
in	0
detrimental	0
neuroplasticity	0
and	0
neuroinflammatory	3
changes	0
that	0
occur	0
following	0
seizures	3
.	0

Metallothionein	1
induction	0
reduces	0
caspase	0
-	0
3	0
activity	0
and	0
TNFalpha	0
levels	0
with	0
preservation	0
of	0
cognitive	0
function	0
and	0
intact	0
hippocampal	0
neurons	0
in	0
carmustine	1
-	0
treated	0
rats	0
.	0

Hippocampal	0
integrity	0
is	0
essential	0
for	0
cognitive	0
functions	0
.	0

0n	0
the	0
other	0
hand	0
,	0
induction	0
of	0
metallothionein	1
(	0
MT	1
)	0
by	0
ZnS0	1
(	2
4	2
)	2
and	0
its	0
role	0
in	0
neuroprotection	0
has	0
been	0
documented	0
.	0

The	0
present	0
study	0
aimed	0
to	0
explore	0
the	0
effect	0
of	0
MT	1
induction	0
on	0
carmustine	1
(	0
BCNU	1
)	0
-	0
induced	0
hippocampal	0
cognitive	3
dysfunction	4
in	0
rats	0
.	0

A	0
total	0
of	0
60	0
male	0
Wistar	0
albino	0
rats	0
were	0
randomly	0
divided	0
into	0
four	0
groups	0
(	0
15	0
/	0
group	0
)	0
:	0
The	0
control	0
group	0
injected	0
with	0
single	0
doses	0
of	0
normal	0
saline	0
(	0
i	0
.	0
c	0
.	0
v	0
)	0
followed	0
24	0
h	0
later	0
by	0
BCNU	1
solvent	0
(	0
i	0
.	0
v	0
)	0
.	0

The	0
second	0
group	0
administered	0
ZnS0	1
(	2
4	2
)	2
(	0
0	0
.	0
1	0
micromol	0
/	0
10	0
microl	0
normal	0
saline	0
,	0
i	0
.	0
c	0
.	0
v	0
,	0
once	0
)	0
then	0
BCNU	1
solvent	0
(	0
i	0
.	0
v	0
)	0
after	0
24	0
h	0
.	0

Third	0
group	0
received	0
BCNU	1
(	0
20	0
mg	0
/	0
kg	0
,	0
i	0
.	0
v	0
,	0
once	0
)	0
24	0
h	0
after	0
injection	0
with	0
normal	0
saline	0
(	0
i	0
.	0
c	0
.	0
v	0
)	0
.	0

Fourth	0
group	0
received	0
a	0
single	0
dose	0
of	0
ZnS0	1
(	2
4	2
)	2
(	0
0	0
.	0
1	0
micromol	0
/	0
10	0
microl	0
normal	0
saline	0
,	0
i	0
.	0
c	0
.	0
v	0
)	0
then	0
BCNU	1
(	0
20	0
mg	0
/	0
kg	0
,	0
i	0
.	0
v	0
,	0
once	0
)	0
after	0
24	0
h	0
.	0

The	0
obtained	0
data	0
revealed	0
that	0
BCNU	1
administration	0
resulted	0
in	0
deterioration	3
of	4
learning	4
and	4
short	4
-	4
term	4
memory	4
(	0
STM	0
)	0
,	0
as	0
measured	0
by	0
using	0
radial	0
arm	0
water	0
maze	0
,	0
accompanied	0
with	0
decreased	0
hippocampal	0
glutathione	1
reductase	0
(	0
GR	0
)	0
activity	0
and	0
reduced	0
glutathione	1
(	0
GSH	1
)	0
content	0
.	0

Also	0
,	0
BCNU	1
administration	0
increased	0
serum	0
tumor	3
necrosis	3
factor	0
-	0
alpha	0
(	0
TNFalpha	0
)	0
,	0
hippocampal	0
MT	1
and	0
malondialdehyde	1
(	0
MDA	1
)	0
contents	0
as	0
well	0
as	0
caspase	0
-	0
3	0
activity	0
in	0
addition	0
to	0
histological	0
alterations	0
.	0

ZnS0	1
(	2
4	2
)	2
pretreatment	0
counteracted	0
BCNU	1
-	0
induced	0
inhibition	0
of	0
GR	0
and	0
depletion	0
of	0
GSH	1
and	0
resulted	0
in	0
significant	0
reduction	0
in	0
the	0
levels	0
of	0
MDA	1
and	0
TNFalpha	0
as	0
well	0
as	0
the	0
activity	0
of	0
caspase	0
-	0
3	0
.	0

The	0
histological	0
features	0
were	0
improved	0
in	0
hippocampus	0
of	0
rats	0
treated	0
with	0
ZnS0	1
(	2
4	2
)	2
+	0
BCNU	1
compared	0
to	0
only	0
BCNU	1
-	0
treated	0
animals	0
.	0

In	0
conclusion	0
,	0
MT	1
induction	0
halts	0
BCNU	1
-	0
induced	0
hippocampal	0
toxicity	3
as	0
it	0
prevented	0
GR	0
inhibition	0
and	0
GSH	1
depletion	0
and	0
counteracted	0
the	0
increased	0
levels	0
of	0
TNFalpha	0
,	0
MDA	1
and	0
caspase	0
-	0
3	0
activity	0
with	0
subsequent	0
preservation	0
of	0
cognition	0
.	0

Fatal	0
carbamazepine	1
induced	0
fulminant	3
eosinophilic	4
(	0
hypersensitivity	3
)	0
myocarditis	3
:	0
emphasis	0
on	0
anatomical	0
and	0
histological	0
characteristics	0
,	0
mechanisms	0
and	0
genetics	0
of	0
drug	3
hypersensitivity	4
and	0
differential	0
diagnosis	0
.	0

The	0
most	0
severe	0
adverse	0
reactions	0
to	0
carbamazepine	1
have	0
been	0
observed	0
in	0
the	0
haemopoietic	0
system	0
,	0
the	0
liver	0
and	0
the	0
cardiovascular	0
system	0
.	0

A	0
frequently	0
fatal	0
,	0
although	0
exceptionally	0
rare	0
side	0
effect	0
of	0
carbamazepine	1
is	0
necrotizing	0
eosinophilic	0
(	0
hypersensitivity	3
)	0
myocarditis	3
.	0

We	0
report	0
a	0
case	0
of	0
hypersensitivity	3
myocarditis	3
secondary	0
to	0
administration	0
of	0
carbamazepine	1
.	0

Acute	0
hypersensitivity	3
myocarditis	3
was	0
not	0
suspected	0
clinically	0
,	0
and	0
the	0
diagnosis	0
was	0
made	0
post	0
-	0
mortem	0
.	0

Histology	0
revealed	0
diffuse	0
infiltration	0
of	0
the	0
myocardium	0
by	0
eosinophils	0
and	0
lymphocytes	0
with	0
myocyte	0
damage	0
.	0

Clinically	0
,	0
death	0
was	0
due	0
to	0
cardiogenic	3
shock	4
.	0

To	0
best	0
of	0
our	0
knowledge	0
this	0
is	0
the	0
second	0
case	0
of	0
fatal	0
carbamazepine	1
induced	0
myocarditis	3
reported	0
in	0
English	0
literature	0
.	0

Neuropsychiatric	0
behaviors	0
in	0
the	0
MPTP	1
marmoset	0
model	0
of	0
Parkinson	3
'	4
s	4
disease	4
.	0

0BJECTIVES	0
:	0
Neuropsychiatric	0
symptoms	0
are	0
increasingly	0
recognised	0
as	0
a	0
significant	0
problem	0
in	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
.	0

These	0
symptoms	0
may	0
be	0
due	0
to	0
'	0
sensitisation	0
'	0
following	0
repeated	0
levodopa	1
treatment	0
or	0
a	0
direct	0
effect	0
of	0
dopamine	1
on	0
the	0
disease	0
state	0
.	0

The	0
levodopa	1
-	0
treated	0
MPTP	1
-	0
lesioned	0
marmoset	0
was	0
used	0
as	0
a	0
model	0
of	0
neuropsychiatric	3
symptoms	4
in	0
PD	3
patients	0
.	0

Here	0
we	0
compare	0
the	0
time	0
course	0
of	0
levodopa	1
-	0
induced	0
motor	0
fluctuations	0
and	0
neuropsychiatric	3
-	4
like	4
behaviors	4
to	0
determine	0
the	0
relationship	0
between	0
duration	0
of	0
treatment	0
and	0
onset	0
of	0
symptoms	0
.	0

METH0DS	0
:	0
Marmosets	0
were	0
administered	0
1	1
-	2
methyl	2
-	2
4	2
-	2
phenyl	2
-	2
1	2
,	2
2	2
,	2
3	2
,	2
6	2
-	2
tetrahydropyridine	2
(	0
2	0
.	0
0	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
for	0
five	0
days	0
,	0
resulting	0
in	0
stable	0
parkinsonism	3
.	0

Levodopa	1
(	0
15	0
mg	0
/	0
kg	0
and	0
benserazide	1
,	0
3	0
.	0
75	0
mg	0
/	0
kg	0
)	0
p	0
.	0
o	0
.	0

b	0
.	0
i	0
.	0
d	0
,	0
was	0
administered	0
for	0
30	0
days	0
.	0

Animals	0
were	0
evaluated	0
for	0
parkinsonian	3
disability	4
,	0
dyskinesia	3
and	0
on	0
-	0
time	0
(	0
motor	0
fluctuations	0
)	0
and	0
neuropsychiatric	3
-	4
like	4
behaviors	4
on	0
Day	0
0	0
(	0
prior	0
to	0
levodopa	1
)	0
and	0
on	0
Days	0
1	0
,	0
7	0
,	0
13	0
,	0
27	0
and	0
30	0
of	0
treatment	0
using	0
post	0
hoc	0
DVD	0
analysis	0
by	0
a	0
trained	0
rater	0
,	0
blind	0
to	0
the	0
treatment	0
day	0
.	0

RESULTS	0
:	0
The	0
neuropsychiatric	3
-	4
like	4
behavior	4
rating	0
scale	0
demonstrated	0
high	0
interrater	0
reliability	0
between	0
three	0
trained	0
raters	0
of	0
differing	0
professional	0
backgrounds	0
.	0

As	0
anticipated	0
,	0
animals	0
exhibited	0
a	0
progressive	0
increase	0
in	0
levodopa	1
-	0
induced	0
motor	0
fluctuations	0
,	0
dyskinesia	3
and	0
wearing	0
-	0
off	0
,	0
that	0
correlated	0
with	0
the	0
duration	0
of	0
levodopa	1
therapy	0
.	0

In	0
contrast	0
,	0
levodopa	1
-	0
induced	0
neuropsychiatric	3
-	4
like	4
behaviors	4
were	0
present	0
on	0
Day	0
1	0
of	0
levodopa	1
treatment	0
and	0
their	0
severity	0
did	0
not	0
correlate	0
with	0
duration	0
of	0
treatment	0
.	0

C0NCLUSI0NS	0
:	0
The	0
data	0
suggest	0
that	0
neuropsychiatric	3
disorders	4
in	0
PD	3
are	0
more	0
likely	0
an	0
interaction	0
between	0
levodopa	1
and	0
the	0
disease	0
state	0
than	0
a	0
consequence	0
of	0
sensitisation	0
to	0
repeated	0
dopaminergic	0
therapy	0
.	0

Contrast	1
medium	2
nephrotoxicity	3
after	0
renal	0
artery	0
and	0
coronary	0
angioplasty	0
.	0

BACKGR0UND	0
:	0
Renal	3
dysfunction	4
induced	0
by	0
iodinated	0
contrast	1
medium	2
(	0
CM	1
)	0
administration	0
can	0
minimize	0
the	0
benefit	0
of	0
the	0
interventional	0
procedure	0
in	0
patients	0
undergoing	0
renal	0
angioplasty	0
(	0
PTRA	0
)	0
.	0

PURP0SE	0
:	0
To	0
compare	0
the	0
susceptibility	0
to	0
nephrotoxic	3
effect	0
of	0
CM	1
in	0
patients	0
undergoing	0
PTRA	0
with	0
that	0
of	0
patients	0
submitted	0
to	0
percutaneous	0
coronary	0
intervention	0
(	0
PCI	0
)	0
.	0

MATERIAL	0
AND	0
METH0DS	0
:	0
A	0
total	0
of	0
33	0
patients	0
successfully	0
treated	0
with	0
PTRA	0
(	0
PTRA	0
group	0
,	0
mean	0
age	0
70	0
+	0
/	0
-	0
12	0
years	0
,	0
23	0
female	0
,	0
basal	0
creatinine	1
1	0
.	0
46	0
+	0
/	0
-	0
0	0
.	0
79	0
,	0
range	0
0	0
.	0
7	0
-	0
4	0
.	0
9	0
mg	0
/	0
dl	0
)	0
were	0
compared	0
with	0
33	0
patients	0
undergoing	0
successful	0
PCI	0
(	0
PCI	0
group	0
)	0
,	0
matched	0
for	0
basal	0
creatinine	1
(	0
1	0
.	0
44	0
+	0
/	0
-	0
0	0
.	0
6	0
,	0
range	0
0	0
.	0
7	0
-	0
3	0
.	0
4	0
mg	0
/	0
dl	0
)	0
,	0
gender	0
,	0
and	0
age	0
.	0

In	0
both	0
groups	0
postprocedural	0
(	0
48	0
h	0
)	0
serum	0
creatinine	1
was	0
measured	0
.	0

RESULTS	0
:	0
Postprocedural	0
creatinine	1
level	0
decreased	0
nonsignificantly	0
in	0
the	0
PTRA	0
group	0
(	0
1	0
.	0
46	0
+	0
/	0
-	0
0	0
.	0
8	0
vs	0
.	0
1	0
.	0
34	0
+	0
/	0
-	0
0	0
.	0
5	0
mg	0
/	0
dl	0
,	0
P	0
=	0
NS	0
)	0
and	0
increased	0
significantly	0
in	0
the	0
PCI	0
group	0
(	0
1	0
.	0
44	0
+	0
/	0
-	0
0	0
.	0
6	0
vs	0
.	0
1	0
.	0
57	0
+	0
/	0
-	0
0	0
.	0
7	0
mg	0
/	0
dl	0
,	0
P	0
<	0
0	0
.	0
02	0
)	0
.	0

Changes	0
in	0
serum	0
creatinine	1
after	0
intervention	0
(	0
after	0
-	0
before	0
)	0
were	0
significantly	0
different	0
between	0
the	0
PTRA	0
and	0
PCI	0
groups	0
(	0
-	0
0	0
.	0
12	0
+	0
/	0
-	0
0	0
.	0
5	0
vs	0
.	0
0	0
.	0
13	0
+	0
/	0
-	0
0	0
.	0
3	0
,	0
P	0
=	0
0	0
.	0
014	0
)	0
.	0

This	0
difference	0
was	0
not	0
related	0
to	0
either	0
a	0
different	0
clinical	0
risk	0
profile	0
or	0
to	0
the	0
volume	0
of	0
CM	1
administered	0
.	0

C0NCLUSI0N	0
:	0
In	0
this	0
preliminary	0
study	0
patients	0
submitted	0
to	0
PTRA	0
showed	0
a	0
lower	0
susceptibility	0
to	0
renal	3
damage	4
induced	0
by	0
CM	1
administration	0
than	0
PCI	0
patients	0
.	0

The	0
effectiveness	0
of	0
PTRA	0
on	0
renal	0
function	0
seems	0
to	0
be	0
barely	0
influenced	0
by	0
CM	1
toxicity	3
.	0

Diphenhydramine	1
prevents	0
the	0
haemodynamic	0
changes	0
of	0
cimetidine	1
in	0
ICU	0
patients	0
.	0

Cimetidine	1
,	0
a	0
histamine	1
2	0
(	0
H2	0
)	0
antagonist	0
,	0
produces	0
a	0
decrease	0
in	0
arterial	0
pressure	0
due	0
to	0
vasodilatation	0
,	0
especially	0
in	0
critically	0
ill	0
patients	0
.	0

This	0
may	0
be	0
because	0
cimetidine	1
acts	0
as	0
a	0
histamine	1
agonist	0
.	0

We	0
,	0
therefore	0
,	0
investigated	0
the	0
effects	0
of	0
the	0
histamine	1
1	0
(	0
H1	0
)	0
receptor	0
antagonist	0
,	0
diphenhydramine	1
,	0
on	0
the	0
haemodynamic	0
changes	0
observed	0
after	0
cimetidine	1
in	0
ICU	0
patients	0
.	0

Each	0
patient	0
was	0
studied	0
on	0
two	0
separate	0
days	0
.	0

In	0
a	0
random	0
fashion	0
,	0
they	0
received	0
cimetidine	1
200	0
mg	0
iv	0
on	0
one	0
day	0
,	0
and	0
on	0
the	0
other	0
,	0
a	0
pretreatment	0
of	0
diphenhydramine	1
40	0
mg	0
iv	0
with	0
cimetidine	1
200	0
mg	0
iv	0
.	0

In	0
the	0
non	0
-	0
pretreatment	0
group	0
,	0
mean	0
arterial	0
pressure	0
(	0
MAP	0
)	0
decreased	0
from	0
107	0
.	0
4	0
+	0
/	0
-	0
8	0
.	0
4	0
mmHg	0
to	0
86	0
.	0
7	0
+	0
/	0
-	0
11	0
.	0
4	0
mmHg	0
(	0
P	0
less	0
than	0
0	0
.	0
01	0
)	0
two	0
minutes	0
after	0
cimetidine	1
.	0

Also	0
,	0
systemic	0
vascular	0
resistance	0
(	0
SVR	0
)	0
decreased	0
during	0
the	0
eight	0
-	0
minute	0
observation	0
period	0
(	0
P	0
less	0
than	0
0	0
.	0
01	0
)	0
.	0

In	0
contrast	0
,	0
in	0
the	0
pretreatment	0
group	0
,	0
little	0
haemodynamic	0
change	0
was	0
seen	0
.	0

We	0
conclude	0
that	0
an	0
H1	0
antagonist	0
may	0
be	0
useful	0
in	0
preventing	0
hypotension	3
caused	0
by	0
iv	0
cimetidine	1
,	0
since	0
the	0
vasodilating	0
activity	0
of	0
cimetidine	1
is	0
mediated	0
,	0
in	0
part	0
,	0
through	0
the	0
H1	0
receptor	0
.	0

Medical	0
and	0
psychiatric	0
outcomes	0
for	0
patients	0
transplanted	0
for	0
acetaminophen	1
-	0
induced	0
acute	3
liver	4
failure	4
:	0
a	0
case	0
-	0
control	0
study	0
.	0

BACKGR0UND	0
:	0
Acetaminophen	1
-	0
induced	0
hepatotoxicity	3
is	0
the	0
most	0
common	0
cause	0
of	0
acute	3
liver	4
failure	4
(	0
ALF	3
)	0
in	0
the	0
UK	0
.	0

Patients	0
often	0
consume	0
the	0
drug	0
with	0
suicidal	0
intent	0
or	0
with	0
a	0
background	0
of	0
substance	0
dependence	0
.	0

AIMS	0
AND	0
METH0DS	0
:	0
We	0
compared	0
the	0
severity	0
of	0
pretransplant	0
illness	0
,	0
psychiatric	0
co	0
-	0
morbidity	0
,	0
medical	0
and	0
psychosocial	0
outcomes	0
of	0
all	0
patients	0
who	0
had	0
undergone	0
liver	0
transplantation	0
(	0
LT	0
)	0
emergently	0
between	0
1999	0
-	0
2004	0
for	0
acetaminophen	1
-	0
induced	0
ALF	3
(	0
n	0
=	0
36	0
)	0
with	0
age	0
-	0
and	0
sex	0
-	0
matched	0
patients	0
undergoing	0
emergent	0
LT	0
for	0
non	0
-	0
acetaminophen	1
-	0
induced	0
ALF	3
(	0
n	0
=	0
35	0
)	0
and	0
elective	0
LT	0
for	0
chronic	3
liver	4
disease	4
(	0
CLD	3
,	0
n	0
=	0
34	0
)	0
.	0

RESULTS	0
:	0
Acetaminophen	1
-	0
induced	0
ALF	3
patients	0
undergoing	0
LT	0
had	0
a	0
greater	0
severity	0
of	0
pre	0
-	0
LT	0
illness	0
reflected	0
by	0
higher	0
Acute	0
Physiology	0
and	0
Chronic	0
Health	0
Evaluation	0
II	0
scores	0
and	0
requirement	0
for	0
organ	0
support	0
compared	0
with	0
the	0
other	0
two	0
groups	0
.	0

Twenty	0
(	0
56	0
%	0
)	0
acetaminophen	1
-	0
induced	0
ALF	3
patients	0
had	0
a	0
formal	0
psychiatric	0
diagnosis	0
before	0
LT	0
(	0
non	0
-	0
acetaminophen	1
-	0
induced	0
ALF	3
=	0
0	0
/	0
35	0
,	0
CLD	3
=	0
2	0
/	0
34	0
;	0
P	0
<	0
0	0
.	0
01	0
for	0
all	0
)	0
and	0
nine	0
(	0
25	0
%	0
)	0
had	0
a	0
previous	0
suicide	0
attempt	0
.	0

During	0
follow	0
-	0
up	0
(	0
median	0
5	0
years	0
)	0
,	0
there	0
were	0
no	0
significant	0
differences	0
in	0
rejection	0
(	0
acute	0
and	0
chronic	0
)	0
,	0
graft	0
failure	0
or	0
survival	0
between	0
the	0
groups	0
(	0
acetaminophen	1
-	0
induced	0
ALF	3
1	0
year	0
87	0
%	0
,	0
5	0
years	0
75	0
%	0
;	0
non	0
-	0
acetaminophen	1
-	0
induced	0
ALF	3
88	0
%	0
,	0
78	0
%	0
;	0
CLD	3
93	0
%	0
,	0
82	0
%	0
:	0
P	0
>	0
0	0
.	0
6	0
log	0
rank	0
)	0
.	0

Two	0
acetaminophen	1
-	0
induced	0
ALF	3
patients	0
reattempted	0
suicide	0
post	0
-	0
LT	0
(	0
one	0
died	0
8	0
years	0
post	0
-	0
LT	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Despite	0
a	0
high	0
prevalence	0
of	0
psychiatric	0
disturbance	0
,	0
outcomes	0
for	0
patients	0
transplanted	0
emergently	0
for	0
acetaminophen	1
-	0
induced	0
ALF	3
were	0
comparable	0
to	0
those	0
transplanted	0
for	0
non	0
-	0
acetaminophen	1
-	0
induced	0
ALF	3
and	0
electively	0
for	0
CLD	3
.	0

Multidisciplinary	0
approaches	0
with	0
long	0
-	0
term	0
psychiatric	0
follow	0
-	0
up	0
may	0
contribute	0
to	0
low	0
post	0
-	0
transplant	0
suicide	0
rates	0
seen	0
and	0
low	0
rates	0
of	0
graft	0
loss	0
because	0
of	0
non	0
-	0
compliance	0
.	0

Antithrombotic	0
drug	0
use	0
,	0
cerebral	3
microbleeds	4
,	0
and	0
intracerebral	3
hemorrhage	4
:	0
a	0
systematic	0
review	0
of	0
published	0
and	0
unpublished	0
studies	0
.	0

BACKGR0UND	0
AND	0
PURP0SE	0
:	0
Cerebral	3
microbleeds	4
(	0
MB	3
)	0
are	0
potential	0
risk	0
factors	0
for	0
intracerebral	3
hemorrhage	4
(	0
ICH	3
)	0
,	0
but	0
it	0
is	0
unclear	0
if	0
they	0
are	0
a	0
contraindication	0
to	0
using	0
antithrombotic	0
drugs	0
.	0

Insights	0
could	0
be	0
gained	0
by	0
pooling	0
data	0
on	0
MB	3
frequency	0
stratified	0
by	0
antithrombotic	0
use	0
in	0
cohorts	0
with	0
ICH	3
and	0
ischemic	3
stroke	4
(	0
IS	3
)	0
/	0
transient	3
ischemic	4
attack	4
(	0
TIA	3
)	0
.	0

METH0DS	0
:	0
We	0
performed	0
a	0
systematic	0
review	0
of	0
published	0
and	0
unpublished	0
data	0
from	0
cohorts	0
with	0
stroke	3
or	0
TIA	3
to	0
compare	0
the	0
presence	0
of	0
MB	3
in	0
:	0
(	0
1	0
)	0
antithrombotic	0
users	0
vs	0
nonantithrombotic	0
users	0
with	0
ICH	3
;	0
(	0
2	0
)	0
antithrombotic	0
users	0
vs	0
nonusers	0
with	0
IS	3
/	0
TIA	3
;	0
and	0
(	0
3	0
)	0
ICH	3
vs	0
ischemic	3
events	0
stratified	0
by	0
antithrombotic	0
use	0
.	0

We	0
also	0
analyzed	0
published	0
and	0
unpublished	0
follow	0
-	0
up	0
data	0
to	0
determine	0
the	0
risk	0
of	0
ICH	3
in	0
antithrombotic	0
users	0
with	0
MB	3
.	0

RESULTS	0
:	0
In	0
a	0
pooled	0
analysis	0
of	0
1460	0
ICH	3
and	0
3817	0
IS	3
/	0
TIA	3
,	0
MB	3
were	0
more	0
frequent	0
in	0
ICH	3
vs	0
IS	3
/	0
TIA	3
in	0
all	0
treatment	0
groups	0
,	0
but	0
the	0
excess	0
increased	0
from	0
2	0
.	0
8	0
(	0
odds	0
ratio	0
;	0
range	0
,	0
2	0
.	0
3	0
-	0
3	0
.	0
5	0
)	0
in	0
nonantithrombotic	0
users	0
to	0
5	0
.	0
7	0
(	0
range	0
,	0
3	0
.	0
4	0
-	0
9	0
.	0
7	0
)	0
in	0
antiplatelet	0
users	0
and	0
8	0
.	0
0	0
(	0
range	0
,	0
3	0
.	0
5	0
-	0
17	0
.	0
8	0
)	0
in	0
warfarin	1
users	0
(	0
P	0
difference	0
=	0
0	0
.	0
01	0
)	0
.	0

There	0
was	0
also	0
an	0
excess	0
of	0
MB	3
in	0
warfarin	1
users	0
vs	0
nonusers	0
with	0
ICH	3
(	0
0R	0
,	0
2	0
.	0
7	0
;	0
95	0
%	0
CI	0
,	0
1	0
.	0
6	0
-	0
4	0
.	0
4	0
;	0
P	0
<	0
0	0
.	0
001	0
)	0
but	0
none	0
in	0
warfarin	1
users	0
with	0
IS	3
/	0
TIA	3
(	0
0R	0
,	0
1	0
.	0
3	0
;	0
95	0
%	0
CI	0
,	0
0	0
.	0
9	0
-	0
1	0
.	0
7	0
;	0
P	0
=	0
0	0
.	0
33	0
;	0
P	0
difference	0
=	0
0	0
.	0
01	0
)	0
.	0

There	0
was	0
a	0
smaller	0
excess	0
of	0
MB	3
in	0
antiplatelet	0
users	0
vs	0
nonusers	0
with	0
ICH	3
(	0
0R	0
,	0
1	0
.	0
7	0
;	0
95	0
%	0
CI	0
,	0
1	0
.	0
3	0
-	0
2	0
.	0
3	0
;	0
P	0
<	0
0	0
.	0
001	0
)	0
,	0
but	0
findings	0
were	0
similar	0
for	0
antiplatelet	0
users	0
with	0
IS	3
/	0
TIA	3
(	0
0R	0
,	0
1	0
.	0
4	0
;	0
95	0
%	0
CI	0
,	0
1	0
.	0
2	0
-	0
1	0
.	0
7	0
;	0
P	0
<	0
0	0
.	0
001	0
;	0
P	0
difference	0
=	0
0	0
.	0
25	0
)	0
.	0

In	0
pooled	0
follow	0
-	0
up	0
data	0
for	0
768	0
antithrombotic	0
users	0
,	0
presence	0
of	0
MB	3
at	0
baseline	0
was	0
associated	0
with	0
a	0
substantially	0
increased	0
risk	0
of	0
subsequent	0
ICH	3
(	0
0R	0
,	0
12	0
.	0
1	0
;	0
95	0
%	0
CI	0
,	0
3	0
.	0
4	0
-	0
42	0
.	0
5	0
;	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

C0NCLUSI0NS	0
:	0
The	0
excess	0
of	0
MB	3
in	0
warfarin	1
users	0
with	0
ICH	3
compared	0
to	0
other	0
groups	0
suggests	0
that	0
MB	3
increase	0
the	0
risk	0
of	0
warfarin	1
-	0
associated	0
ICH	3
.	0

Limited	0
prospective	0
data	0
corroborate	0
these	0
findings	0
,	0
but	0
larger	0
prospective	0
studies	0
are	0
urgently	0
required	0
.	0

Studies	0
of	0
synergy	0
between	0
morphine	1
and	0
a	0
novel	0
sodium	1
channel	0
blocker	0
,	0
CNSB002	1
,	0
in	0
rat	0
models	0
of	0
inflammatory	0
and	0
neuropathic	3
pain	4
.	0

0BJECTIVE	0
:	0
This	0
study	0
determined	0
the	0
antihyperalgesic	0
effect	0
of	0
CNSB002	1
,	0
a	0
sodium	1
channel	0
blocker	0
with	0
antioxidant	0
properties	0
given	0
alone	0
and	0
in	0
combinations	0
with	0
morphine	1
in	0
rat	0
models	0
of	0
inflammatory	0
and	0
neuropathic	3
pain	4
.	0

DESIGN	0
:	0
Dose	0
response	0
curves	0
for	0
nonsedating	0
doses	0
of	0
morphine	1
and	0
CNSB002	1
given	0
intraperitoneally	0
alone	0
and	0
together	0
in	0
combinations	0
were	0
constructed	0
for	0
antihyperalgesic	0
effect	0
using	0
paw	0
withdrawal	0
from	0
noxious	0
heat	0
in	0
two	0
rat	0
pain	3
models	0
:	0
carrageenan	1
-	0
induced	0
paw	0
inflammation	3
and	0
streptozotocin	1
(	0
STZ	1
)	0
-	0
induced	0
diabetic	3
neuropathy	4
.	0

RESULTS	0
:	0
The	0
maximum	0
nonsedating	0
doses	0
were	0
:	0
morphine	1
,	0
3	0
.	0
2	0
mg	0
/	0
kg	0
;	0
CNSB002	1
10	0
.	0
0	0
mg	0
/	0
kg	0
;	0
5	0
.	0
0	0
mg	0
/	0
kg	0
CNSB002	1
with	0
morphine	1
3	0
.	0
2	0
mg	0
/	0
kg	0
in	0
combination	0
.	0

The	0
doses	0
calculated	0
to	0
cause	0
50	0
%	0
reversal	0
of	0
hyperalgesia	3
(	0
ED50	0
)	0
were	0
7	0
.	0
54	0
(	0
1	0
.	0
81	0
)	0
and	0
4	0
.	0
83	0
(	0
1	0
.	0
54	0
)	0
in	0
the	0
carrageenan	1
model	0
and	0
44	0
.	0
18	0
(	0
1	0
.	0
37	0
)	0
and	0
9	0
.	0
14	0
(	0
1	0
.	0
24	0
)	0
in	0
the	0
STZ	1
-	0
induced	0
neuropathy	3
model	0
for	0
CNSB002	1
and	0
morphine	1
,	0
respectively	0
(	0
mg	0
/	0
kg	0
;	0
mean	0
,	0
SEM	0
)	0
.	0

These	0
values	0
were	0
greater	0
than	0
the	0
maximum	0
nonsedating	0
doses	0
.	0

The	0
ED50	0
values	0
for	0
morphine	1
when	0
given	0
in	0
combination	0
with	0
CNSB002	1
(	0
5	0
mg	0
/	0
kg	0
)	0
were	0
less	0
than	0
the	0
maximum	0
nonsedating	0
dose	0
:	0
0	0
.	0
56	0
(	0
1	0
.	0
55	0
)	0
in	0
the	0
carrageenan	1
model	0
and	0
1	0
.	0
37	0
(	0
1	0
.	0
23	0
)	0
in	0
the	0
neuropathy	3
model	0
(	0
mg	0
/	0
kg	0
;	0
mean	0
,	0
SEM	0
)	0
.	0

The	0
antinociception	0
after	0
morphine	1
(	0
3	0
.	0
2	0
mg	0
/	0
kg	0
)	0
was	0
increased	0
by	0
co	0
-	0
administration	0
with	0
CNSB002	1
from	0
28	0
.	0
0	0
and	0
31	0
.	0
7	0
%	0
to	0
114	0
.	0
6	0
and	0
56	0
.	0
9	0
%	0
reversal	0
of	0
hyperalgesia	3
in	0
the	0
inflammatory	0
and	0
neuropathic	3
models	0
,	0
respectively	0
(	0
P	0
<	0
0	0
.	0
01	0
;	0
one	0
-	0
way	0
analysis	0
of	0
variance	0
-	0
significantly	0
greater	0
than	0
either	0
drug	0
given	0
alone	0
)	0
.	0

C0NCLUSI0NS	0
:	0
The	0
maximum	0
antihyperalgesic	0
effect	0
achievable	0
with	0
nonsedating	0
doses	0
of	0
morphine	1
may	0
be	0
increased	0
significantly	0
when	0
the	0
drug	0
is	0
used	0
in	0
combination	0
with	0
CNSB002	1
.	0

Heparin	1
-	0
induced	0
thrombocytopenia	3
:	0
a	0
practical	0
review	0
.	0

Heparin	1
-	0
induced	0
thrombocytopenia	3
(	0
HIT	3
)	0
remains	0
under	0
-	0
recognized	0
despite	0
its	0
potentially	0
devastating	0
outcomes	0
.	0

It	0
begins	0
when	0
heparin	1
exposure	0
stimulates	0
the	0
formation	0
of	0
heparin	1
-	0
platelet	0
factor	0
4	0
antibodies	0
,	0
which	0
in	0
turn	0
triggers	0
the	0
release	0
of	0
procoagulant	0
platelet	0
particles	0
.	0

Thrombosis	3
and	0
thrombocytopenia	3
that	0
follow	0
comprise	0
the	0
2	0
hallmark	0
traits	0
of	0
HIT	3
,	0
with	0
the	0
former	0
largely	0
responsible	0
for	0
significant	0
vascular	0
complications	0
.	0

The	0
prevalence	0
of	0
HIT	3
varies	0
among	0
several	0
subgroups	0
,	0
with	0
greater	0
incidence	0
in	0
surgical	0
as	0
compared	0
with	0
medical	0
populations	0
.	0

HIT	3
must	0
be	0
acknowledged	0
for	0
its	0
intense	0
predilection	0
for	0
thrombosis	3
and	0
suspected	0
whenever	0
thrombosis	3
occurs	0
after	0
heparin	1
exposure	0
.	0

Early	0
recognition	0
that	0
incorporates	0
the	0
clinical	0
and	0
serologic	0
clues	0
is	0
paramount	0
to	0
timely	0
institution	0
of	0
treatment	0
,	0
as	0
its	0
delay	0
may	0
result	0
in	0
catastrophic	0
outcomes	0
.	0

The	0
treatment	0
of	0
HIT	3
mandates	0
an	0
immediate	0
cessation	0
of	0
all	0
heparin	1
exposure	0
and	0
the	0
institution	0
of	0
an	0
antithrombotic	0
therapy	0
,	0
most	0
commonly	0
using	0
a	0
direct	1
thrombin	2
inhibitor	2
.	0

Current	0
"	0
diagnostic	0
"	0
tests	0
,	0
which	0
primarily	0
include	0
functional	0
and	0
antigenic	0
assays	0
,	0
have	0
more	0
of	0
a	0
confirmatory	0
than	0
diagnostic	0
role	0
in	0
the	0
management	0
of	0
HIT	3
.	0

Special	0
attention	0
must	0
be	0
paid	0
to	0
cardiac	0
patients	0
who	0
are	0
often	0
exposed	0
to	0
heparin	1
multiple	0
times	0
during	0
their	0
course	0
of	0
treatment	0
.	0

Direct	1
thrombin	2
inhibitors	2
are	0
appropriate	0
,	0
evidence	0
-	0
based	0
alternatives	0
to	0
heparin	1
in	0
patients	0
with	0
a	0
history	0
of	0
HIT	3
,	0
who	0
need	0
to	0
undergo	0
percutaneous	0
coronary	0
intervention	0
.	0

As	0
heparin	1
remains	0
one	0
of	0
the	0
most	0
frequently	0
used	0
medications	0
today	0
with	0
potential	0
for	0
HIT	3
with	0
every	0
heparin	1
exposure	0
,	0
a	0
close	0
vigilance	0
of	0
platelet	0
counts	0
must	0
be	0
practiced	0
whenever	0
heparin	1
is	0
initiated	0
.	0

Abductor	0
paralysis	3
after	0
botox	1
injection	0
for	0
adductor	3
spasmodic	4
dysphonia	4
.	0

0BJECTIVES	0
/	0
HYP0THESIS	0
:	0
Botulinum	0
toxin	0
(	0
Botox	1
)	0
injections	0
into	0
the	0
thyroarytenoid	0
muscles	0
are	0
the	0
current	0
standard	0
of	0
care	0
for	0
adductor	3
spasmodic	4
dysphonia	4
(	0
ADSD	3
)	0
.	0

Reported	0
adverse	0
effects	0
include	0
a	0
period	0
of	0
breathiness	0
,	0
throat	3
pain	4
,	0
and	0
difficulty	0
with	0
swallowing	0
liquids	0
.	0

Here	0
we	0
report	0
multiple	0
cases	0
of	0
bilateral	0
abductor	0
paralysis	3
following	0
Botox	1
injections	0
for	0
ADSD	3
,	0
a	0
complication	0
previously	0
unreported	0
.	0

STUDY	0
DESIGN	0
:	0
Retrospective	0
case	0
series	0
.	0

METH0DS	0
:	0
Patients	0
that	0
received	0
Botox	1
injections	0
for	0
spasmodic	3
dysphonia	4
between	0
January	0
2000	0
and	0
0ctober	0
2009	0
were	0
evaluated	0
.	0

Patients	0
with	0
ADSD	3
were	0
identified	0
.	0

The	0
number	0
of	0
treatments	0
received	0
and	0
adverse	0
effects	0
were	0
noted	0
.	0

For	0
patients	0
with	0
bilateral	0
abductor	0
paralysis	3
,	0
age	0
,	0
sex	0
,	0
paralytic	0
Botox	1
dose	0
,	0
prior	0
Botox	1
dose	0
,	0
and	0
course	0
following	0
paralysis	3
were	0
noted	0
.	0

RESULTS	0
:	0
From	0
a	0
database	0
of	0
452	0
patients	0
receiving	0
Botox	1
,	0
352	0
patients	0
had	0
been	0
diagnosed	0
with	0
ADSD	3
.	0

0f	0
these	0
352	0
patients	0
,	0
eight	0
patients	0
suffered	0
bilateral	0
abductor	0
paralysis	3
,	0
and	0
two	0
suffered	0
this	0
complication	0
twice	0
.	0

All	0
affected	0
patients	0
were	0
females	0
over	0
the	0
age	0
of	0
50	0
years	0
.	0

Most	0
patients	0
had	0
received	0
treatments	0
prior	0
to	0
abductor	0
paralysis	3
and	0
continued	0
receiving	0
after	0
paralysis	3
.	0

Seven	0
patients	0
recovered	0
after	0
a	0
brief	0
period	0
of	0
activity	0
restrictions	0
,	0
and	0
one	0
underwent	0
a	0
tracheotomy	0
.	0

The	0
incidence	0
of	0
abductor	0
paralysis	3
after	0
Botox	1
injection	0
for	0
ADSD	3
was	0
0	0
.	0
34	0
%	0
.	0

C0NCLUSI0NS	0
:	0
Bilateral	0
abductor	0
paralysis	3
is	0
a	0
rare	0
complication	0
of	0
Botox	1
injections	0
for	0
ADSD	3
,	0
causing	0
difficulty	0
with	0
breathing	0
upon	0
exertion	0
.	0

The	0
likely	0
mechanism	0
of	0
paralysis	3
is	0
diffusion	0
of	0
Botox	1
around	0
the	0
muscular	0
process	0
of	0
the	0
arytenoid	0
to	0
the	0
posterior	0
cricoarytenoid	0
muscles	0
.	0

The	0
paralysis	3
is	0
temporary	0
,	0
and	0
watchful	0
waiting	0
with	0
restriction	0
of	0
activity	0
is	0
the	0
recommended	0
management	0
.	0

Mitochondrial	3
impairment	4
contributes	0
to	0
cocaine	1
-	0
induced	0
cardiac	3
dysfunction	4
:	0
Prevention	0
by	0
the	0
targeted	0
antioxidant	0
MitoQ	1
.	0

The	0
goal	0
of	0
this	0
study	0
was	0
to	0
assess	0
mitochondrial	0
function	0
and	0
R0S	0
production	0
in	0
an	0
experimental	0
model	0
of	0
cocaine	1
-	0
induced	0
cardiac	3
dysfunction	4
.	0

We	0
hypothesized	0
that	0
cocaine	3
abuse	4
may	0
lead	0
to	0
altered	0
mitochondrial	0
function	0
that	0
in	0
turn	0
may	0
cause	0
left	3
ventricular	4
dysfunction	4
.	0

Seven	0
days	0
of	0
cocaine	1
administration	0
to	0
rats	0
led	0
to	0
an	0
increased	0
oxygen	1
consumption	0
detected	0
in	0
cardiac	0
fibers	0
,	0
specifically	0
through	0
complex	0
I	0
and	0
complex	0
III	0
.	0

R0S	0
levels	0
were	0
increased	0
,	0
specifically	0
in	0
interfibrillar	0
mitochondria	0
.	0

In	0
parallel	0
there	0
was	0
a	0
decrease	0
in	0
ATP	1
synthesis	0
,	0
whereas	0
no	0
difference	0
was	0
observed	0
in	0
subsarcolemmal	0
mitochondria	0
.	0

This	0
uncoupling	0
effect	0
on	0
oxidative	0
phosphorylation	0
was	0
not	0
detectable	0
after	0
short	0
-	0
term	0
exposure	0
to	0
cocaine	1
,	0
suggesting	0
that	0
these	0
mitochondrial	3
abnormalities	4
were	0
a	0
late	0
rather	0
than	0
a	0
primary	0
event	0
in	0
the	0
pathological	0
response	0
to	0
cocaine	1
.	0

MitoQ	1
,	0
a	0
mitochondrial	0
-	0
targeted	0
antioxidant	0
,	0
was	0
shown	0
to	0
completely	0
prevent	0
these	0
mitochondrial	3
abnormalities	4
as	0
well	0
as	0
cardiac	3
dysfunction	4
characterized	0
here	0
by	0
a	0
diastolic	3
dysfunction	4
studied	0
with	0
a	0
conductance	0
catheter	0
to	0
obtain	0
pressure	0
-	0
volume	0
data	0
.	0

Taken	0
together	0
,	0
these	0
results	0
extend	0
previous	0
studies	0
and	0
demonstrate	0
that	0
cocaine	1
-	0
induced	0
cardiac	3
dysfunction	4
may	0
be	0
due	0
to	0
a	0
mitochondrial	3
defect	4
.	0

Trimethoprim	1
-	0
induced	0
immune	0
hemolytic	3
anemia	4
in	0
a	0
pediatric	0
oncology	0
patient	0
presenting	0
as	0
an	0
acute	0
hemolytic	0
transfusion	0
reaction	0
.	0

A	0
10	0
-	0
year	0
-	0
old	0
male	0
with	0
acute	3
leukemia	4
presented	0
with	0
post	0
-	0
chemotherapy	0
anemia	3
.	0

During	0
red	0
cell	0
transfusion	0
,	0
he	0
developed	0
hemoglobinuria	3
.	0

Transfusion	0
reaction	0
workup	0
was	0
negative	0
.	0

Drug	0
-	0
induced	0
immune	0
hemolytic	3
anemia	4
was	0
suspected	0
because	0
of	0
positive	0
direct	0
antiglobulin	0
test	0
,	0
negative	0
eluate	0
,	0
and	0
microspherocytes	0
on	0
smear	0
pre	0
-	0
and	0
post	0
-	0
transfusion	0
.	0

Drug	0
studies	0
using	0
the	0
indirect	0
antiglobulin	0
test	0
were	0
strongly	0
positive	0
with	0
trimethoprim	1
and	0
trimethoprim	1
-	2
sulfamethoxazole	2
but	0
negative	0
with	0
sulfamethoxazole	1
.	0

The	0
patient	0
recovered	0
after	0
discontinuing	0
the	0
drug	0
,	0
with	0
no	0
recurrence	0
in	0
2	0
years	0
.	0

0ther	0
causes	0
of	0
anemia	3
should	0
be	0
considered	0
in	0
patients	0
with	0
worse	0
-	0
than	0
-	0
expected	0
anemia	3
after	0
chemotherapy	0
.	0

Furthermore	0
,	0
hemolysis	3
during	0
transfusion	0
is	0
not	0
always	0
a	0
transfusion	0
reaction	0
.	0

Verapamil	1
stimulation	0
test	0
in	0
hyperprolactinemia	3
:	0
loss	0
of	0
prolactin	0
response	0
in	0
anatomic	0
or	0
functional	0
stalk	0
effect	0
.	0

AIM	0
:	0
Verapamil	1
stimulation	0
test	0
was	0
previously	0
investigated	0
as	0
a	0
tool	0
for	0
differential	0
diagnosis	0
of	0
hyperprolactinemia	3
,	0
but	0
with	0
conflicting	0
results	0
.	0

Macroprolactinemia	3
was	0
never	0
considered	0
in	0
those	0
previous	0
studies	0
.	0

Here	0
,	0
we	0
aimed	0
to	0
re	0
-	0
investigate	0
the	0
diagnostic	0
value	0
of	0
verapamil	1
in	0
a	0
population	0
who	0
were	0
all	0
screened	0
for	0
macroprolactinemia	3
.	0

Prolactin	0
responses	0
to	0
verapamil	1
in	0
65	0
female	0
patients	0
(	0
age	0
:	0
29	0
.	0
9	0
+	0
/	0
-	0
8	0
.	0
1	0
years	0
)	0
with	0
hyperprolactinemia	3
were	0
tested	0
in	0
a	0
descriptive	0
,	0
matched	0
case	0
-	0
control	0
study	0
.	0

METH0DS	0
:	0
Verapamil	1
80	0
mg	0
,	0
p	0
.	0
o	0
.	0
was	0
administered	0
,	0
and	0
then	0
PRL	0
levels	0
were	0
measured	0
at	0
8th	0
and	0
16th	0
hours	0
,	0
by	0
immunometric	0
chemiluminescence	0
.	0

Verapamil	1
responsiveness	0
was	0
determined	0
by	0
peak	0
percent	0
change	0
in	0
basal	0
prolactin	0
levels	0
(	0
PRL	0
)	0
.	0

RESULTS	0
:	0
Verapamil	1
significantly	0
increased	0
PRL	0
levels	0
in	0
healthy	0
controls	0
(	0
N	0
.	0
8	0
,	0
PRL	0
:	0
183	0
%	0
)	0
,	0
macroprolactinoma	3
(	0
N	0
.	0
8	0
,	0
PRL	0
:	0
7	0
%	0
)	0
,	0
microprolactinoma	3
(	0
N	0
.	0
19	0
,	0
PRL	0
:	0
21	0
%	0
)	0
,	0
macroprolactinemia	3
(	0
N	0
.	0
23	0
,	0
PRL	0
:	0
126	0
%	0
)	0
,	0
but	0
not	0
in	0
pseudoprolactinoma	3
(	0
N	0
.	0
8	0
,	0
PRL	0
:	0
0	0
.	0
8	0
%	0
)	0
,	0
and	0
risperidone	1
-	0
induced	0
hyperprolactinemia	3
(	0
N	0
.	0
7	0
,	0
PRL	0
:	0
3	0
%	0
)	0
.	0

R0C	0
curve	0
analysis	0
revealed	0
that	0
unresponsiveness	0
to	0
verapamil	1
defined	0
as	0
PRL	0
<	0
7	0
%	0
,	0
discriminated	0
anatomical	0
or	0
functional	0
stalk	0
effect	0
(	0
sensitivity	0
:	0
74	0
%	0
,	0
specificity	0
:	0
73	0
%	0
,	0
AUC	0
:	0
0	0
.	0
855	0
+	0
/	0
-	0
0	0
.	0
04	0
,	0
P	0
<	0
0	0
.	0
001	0
,	0
CI	0
:	0
0	0
.	0
768	0
-	0
0	0
.	0
942	0
)	0
associated	0
with	0
pseudoprolactinoma	3
or	0
risperidone	1
-	0
induced	0
hyperprolactinemia	3
,	0
respectively	0
.	0

C0NCLUSI0N	0
:	0
Verapamil	1
responsiveness	0
is	0
not	0
a	0
reliable	0
finding	0
for	0
the	0
differential	0
diagnosis	0
of	0
hyperprolactinemia	3
.	0

However	0
,	0
verapamil	1
unresponsiveness	0
discriminates	0
stalk	0
effect	0
(	0
i	0
.	0
e	0
.	0
,	0
anatomically	0
or	0
functionally	0
inhibited	0
dopaminergic	0
tonus	0
)	0
from	0
other	0
causes	0
of	0
hyperprolactinemia	3
with	0
varying	0
degrees	0
of	0
responsiveness	0
.	0

Blockade	0
of	0
endothelial	0
-	0
mesenchymal	0
transition	0
by	0
a	0
Smad3	0
inhibitor	0
delays	0
the	0
early	0
development	0
of	0
streptozotocin	1
-	0
induced	0
diabetic	3
nephropathy	4
.	0

0BJECTIVE	0
:	0
A	0
multicenter	0
,	0
controlled	0
trial	0
showed	0
that	0
early	0
blockade	0
of	0
the	0
renin	0
-	0
angiotensin	1
system	0
in	0
patients	0
with	0
type	3
1	4
diabetes	4
and	0
normoalbuminuria	0
did	0
not	0
retard	0
the	0
progression	0
of	0
nephropathy	3
,	0
suggesting	0
that	0
other	0
mechanism	0
(	0
s	0
)	0
are	0
involved	0
in	0
the	0
pathogenesis	0
of	0
early	0
diabetic	3
nephropathy	4
(	0
diabetic	3
nephropathy	4
)	0
.	0

We	0
have	0
previously	0
demonstrated	0
that	0
endothelial	0
-	0
mesenchymal	0
-	0
transition	0
(	0
EndoMT	0
)	0
contributes	0
to	0
the	0
early	0
development	0
of	0
renal	0
interstitial	0
fibrosis	3
independently	0
of	0
microalbuminuria	0
in	0
mice	0
with	0
streptozotocin	1
(	0
STZ	1
)	0
-	0
induced	0
diabetes	3
.	0

In	0
the	0
present	0
study	0
,	0
we	0
hypothesized	0
that	0
blocking	0
EndoMT	0
reduces	0
the	0
early	0
development	0
of	0
diabetic	3
nephropathy	4
.	0

RESEARCH	0
DESIGN	0
AND	0
METH0DS	0
:	0
EndoMT	0
was	0
induced	0
in	0
a	0
mouse	0
pancreatic	0
microvascular	0
endothelial	0
cell	0
line	0
(	0
MMEC	0
)	0
in	0
the	0
presence	0
of	0
advanced	0
glycation	0
end	0
products	0
(	0
AGEs	0
)	0
and	0
in	0
the	0
endothelial	0
lineage	0
-	0
traceble	0
mouse	0
line	0
Tie2	0
-	0
Cre	0
;	0
Loxp	0
-	0
EGFP	0
by	0
administration	0
of	0
AGEs	0
,	0
with	0
nonglycated	0
mouse	0
albumin	0
serving	0
as	0
a	0
control	0
.	0

Phosphorylated	0
Smad3	0
was	0
detected	0
by	0
immunoprecipitation	0
/	0
Western	0
blotting	0
and	0
confocal	0
microscopy	0
.	0

Blocking	0
studies	0
using	0
receptor	0
for	0
AGE	0
siRNA	0
and	0
a	0
specific	0
inhibitor	0
of	0
Smad3	0
(	0
SIS3	0
)	0
were	0
performed	0
in	0
MMECs	0
and	0
in	0
STZ	1
-	0
induced	0
diabetic	3
nephropathy	4
in	0
Tie2	0
-	0
Cre	0
;	0
Loxp	0
-	0
EGFP	0
mice	0
.	0

RESULTS	0
:	0
Confocal	0
microscopy	0
and	0
real	0
-	0
time	0
PCR	0
demonstrated	0
that	0
AGEs	0
induced	0
EndoMT	0
in	0
MMECs	0
and	0
in	0
Tie2	0
-	0
Cre	0
;	0
Loxp	0
-	0
EGFP	0
mice	0
.	0

Immunoprecipitation	0
/	0
Western	0
blotting	0
showed	0
that	0
Smad3	0
was	0
activated	0
by	0
AGEs	0
but	0
was	0
inhibited	0
by	0
SIS3	0
in	0
MMECs	0
and	0
in	0
STZ	1
-	0
induced	0
diabetic	3
nephropathy	4
.	0

Confocal	0
microscopy	0
and	0
real	0
-	0
time	0
PCR	0
further	0
demonstrated	0
that	0
SIS3	0
abrogated	0
EndoMT	0
,	0
reduced	0
renal	0
fibrosis	3
,	0
and	0
retarded	0
progression	0
of	0
nephropathy	3
.	0

C0NCLUSI0NS	0
:	0
EndoMT	0
is	0
a	0
novel	0
pathway	0
leading	0
to	0
early	0
development	0
of	0
diabetic	3
nephropathy	4
.	0

Blockade	0
of	0
EndoMT	0
by	0
SIS3	0
may	0
provide	0
a	0
new	0
strategy	0
to	0
retard	0
the	0
progression	0
of	0
diabetic	3
nephropathy	4
and	0
other	0
diabetes	3
complications	4
.	0

Cytostatic	0
and	0
anti	0
-	0
angiogenic	0
effects	0
of	0
temsirolimus	1
in	0
refractory	0
mantle	3
cell	4
lymphoma	4
.	0

Mantle	3
cell	4
lymphoma	4
(	0
MCL	3
)	0
is	0
a	0
rare	0
and	0
aggressive	0
type	0
of	0
B	3
-	4
cell	4
non	4
-	4
Hodgkin	4
'	4
s	4
lymphoma	4
.	0

Patients	0
become	0
progressively	0
refractory	0
to	0
conventional	0
chemotherapy	0
,	0
and	0
their	0
prognosis	0
is	0
poor	0
.	0

However	0
,	0
a	0
38	0
%	0
remission	0
rate	0
has	0
been	0
recently	0
reported	0
in	0
refractory	0
MCL	3
treated	0
with	0
temsirolimus	1
,	0
a	0
mT0R	0
inhibitor	0
.	0
Here	0
we	0
had	0
the	0
opportunity	0
to	0
study	0
a	0
case	0
of	0
refractory	0
MCL	3
who	0
had	0
tumor	3
regression	0
two	0
months	0
after	0
temsirolimus	1
treatment	0
,	0
and	0
a	0
progression	0
-	0
free	0
survival	0
of	0
10	0
months	0
.	0

In	0
this	0
case	0
,	0
lymph	0
node	0
biopsies	0
were	0
performed	0
before	0
and	0
six	0
months	0
after	0
temsirolimus	1
therapy	0
.	0

Comparison	0
of	0
the	0
two	0
biopsies	0
showed	0
that	0
temsirolimus	1
inhibited	0
tumor	3
cell	0
proliferation	0
through	0
cell	0
cycle	0
arrest	0
,	0
but	0
did	0
not	0
induce	0
any	0
change	0
in	0
the	0
number	0
of	0
apoptotic	0
tumor	3
cells	0
.	0

Apart	0
from	0
this	0
cytostatic	0
effect	0
,	0
temsirolimus	1
had	0
an	0
antiangiogenic	0
effect	0
with	0
decrease	0
of	0
tumor	3
microvessel	0
density	0
and	0
of	0
VEGF	0
expression	0
.	0

Moreover	0
,	0
numerous	0
patchy	0
,	0
well	0
-	0
limited	0
fibrotic	0
areas	0
,	0
compatible	0
with	0
post	0
-	0
necrotic	3
tissue	0
repair	0
,	0
were	0
found	0
after	0
6	0
-	0
month	0
temsirolimus	1
therapy	0
.	0

Thus	0
,	0
temsirolimus	1
reduced	0
tumor	3
burden	0
through	0
associated	0
cytostatic	0
and	0
anti	0
-	0
angiogenic	0
effects	0
.	0
This	0
dual	0
effect	0
of	0
temsirolimus	1
on	0
tumor	3
tissue	0
could	0
contribute	0
to	0
its	0
recently	0
reported	0
efficiency	0
in	0
refractory	0
MCL	3
resistant	0
to	0
conventional	0
chemotherapy	0
.	0

Acute	3
renal	4
failure	4
due	0
to	0
rifampicin	1
.	0

A	0
23	0
-	0
year	0
-	0
old	0
male	0
patient	0
with	0
bacteriologically	0
proven	0
pulmonary	3
tuberculosis	4
was	0
treated	0
with	0
the	0
various	0
regimens	0
of	0
antituberculosis	0
drugs	0
for	0
nearly	0
15	0
months	0
.	0

Rifampicin	1
was	0
administered	0
thrice	0
as	0
one	0
of	0
the	0
3	0
-	0
4	0
drug	0
regimen	0
and	0
each	0
time	0
he	0
developed	0
untoward	0
side	0
effects	0
like	0
nausea	3
,	0
vomiting	3
and	0
fever	3
with	0
chills	0
and	0
rigors	0
.	0

The	0
last	0
such	0
episode	0
was	0
of	0
acute	0
renal	0
failure	0
at	0
which	0
stage	0
the	0
patient	0
was	0
seen	0
by	0
the	0
authors	0
of	0
this	0
report	0
.	0

The	0
patient	0
,	0
however	0
,	0
made	0
a	0
full	0
recovery	0
.	0

Syncope	3
caused	0
by	0
hyperkalemia	3
during	0
use	0
of	0
a	0
combined	0
therapy	0
with	0
the	0
angiotensin	1
-	0
converting	0
enzyme	0
inhibitor	0
and	0
spironolactone	1
.	0

A	0
76	0
year	0
-	0
old	0
woman	0
with	0
a	0
history	0
of	0
coronary	0
artery	0
bypass	0
grafting	0
and	0
prior	0
myocardial	3
infarction	4
was	0
transferred	0
to	0
the	0
emergency	0
room	0
with	0
loss	3
of	4
consciousness	4
due	0
to	0
marked	0
bradycardia	3
caused	0
by	0
hyperkalemia	3
.	0

The	0
concentration	0
of	0
serum	0
potassium	1
was	0
high	0
,	0
and	0
normal	0
sinus	0
rhythm	0
was	0
restored	0
after	0
correction	0
of	0
the	0
serum	0
potassium	1
level	0
.	0

The	0
cause	0
of	0
hyperkalemia	3
was	0
considered	0
to	0
be	0
several	0
doses	0
of	0
spiranolactone	1
,	0
an	0
aldosterone	1
antagonist	0
,	0
in	0
addition	0
to	0
the	0
long	0
-	0
term	0
intake	0
of	0
ramipril	1
,	0
an	0
ACE	0
inhibitor	0
.	0

This	0
case	0
is	0
a	0
good	0
example	0
of	0
electrolyte	0
imbalance	0
causing	0
acute	0
life	0
-	0
threatening	0
cardiac	0
events	0
.	0

Clinicians	0
should	0
be	0
alert	0
to	0
the	0
possibility	0
of	0
hyperkalemia	3
,	0
especially	0
in	0
elderly	0
patients	0
using	0
ACE	0
/	0
ARB	0
in	0
combination	0
with	0
potassium	1
sparing	0
agents	0
and	0
who	0
have	0
mild	0
renal	3
disturbance	4
.	0

Diffuse	0
skeletal	0
pain	3
after	0
administration	0
of	0
alendronate	1
.	0

BACKGR0UND	0
:	0
0steoporosis	3
is	0
caused	0
by	0
bone	0
resorption	0
in	0
excess	0
of	0
bone	0
formation	0
,	0
and	0
bisphosphonates	1
,	0
are	0
used	0
to	0
inhibit	0
bone	0
resorption	0
.	0

Alendronate	1
,	0
a	0
biphosphonate	1
,	0
is	0
effective	0
for	0
both	0
the	0
treatment	0
and	0
prevention	0
of	0
osteoporosis	3
in	0
postmenopausal	0
women	0
.	0

Side	0
effects	0
are	0
relatively	0
few	0
and	0
prominently	0
gastrointestinal	0
.	0

Musculoskeletal	3
pain	4
may	0
be	0
an	0
important	0
side	0
effect	0
in	0
these	0
patients	0
.	0

We	0
presented	0
a	0
patient	0
admitted	0
to	0
our	0
out	0
-	0
patient	0
clinic	0
with	0
diffuse	0
skeletal	0
pain	3
after	0
three	0
consecutive	0
administration	0
of	0
alendronate	1
.	0

C0NCLUSI0N	0
:	0
We	0
conclude	0
that	0
patients	0
with	0
osteoporosis	3
can	0
report	0
pain	3
,	0
and	0
bisphosphonate	1
-	0
related	0
pain	3
should	0
also	0
be	0
considered	0
before	0
ascribing	0
this	0
complaint	0
to	0
osteoporosis	3
.	0

Cerebrospinal	0
fluid	0
penetration	0
of	0
high	0
-	0
dose	0
daptomycin	1
in	0
suspected	0
Staphylococcus	0
aureus	0
meningitis	3
.	0

0BJECTIVE	0
:	0
To	0
report	0
a	0
case	0
of	0
methicillin	1
-	0
sensitive	0
Staphylococcus	0
aureus	0
(	0
MSSA	0
)	0
bacteremia	3
with	0
suspected	0
MSSA	0
meningitis	3
treated	0
with	0
high	0
-	0
dose	0
daptomycin	1
assessed	0
with	0
concurrent	0
serum	0
and	0
cerebrospinal	0
fluid	0
(	0
CSF	0
)	0
concentrations	0
.	0

CASE	0
SUMMARY	0
:	0
A	0
54	0
-	0
year	0
-	0
old	0
male	0
presented	0
to	0
the	0
emergency	0
department	0
with	0
generalized	0
weakness	3
and	0
presumed	0
health	0
-	0
care	0
-	0
associated	0
pneumonia	3
shown	0
on	0
chest	0
radiograph	0
.	0

Treatment	0
was	0
empirically	0
initiated	0
with	0
vancomycin	1
,	0
levofloxacin	1
,	0
and	0
piperacillin	1
/	0
tazobactam	1
.	0

Blood	0
cultures	0
revealed	0
S	0
.	0
aureus	0
susceptible	0
to	0
oxacillin	1
.	0

Empiric	0
antibiotic	0
treatment	0
was	0
narrowed	0
to	0
nafcillin	1
on	0
day	0
4	0
.	0

0n	0
day	0
8	0
,	0
the	0
patient	0
developed	0
acute	3
renal	4
failure	4
(	0
serum	0
creatinine	1
1	0
.	0
9	0
mg	0
/	0
dL	0
,	0
increased	0
from	0
1	0
.	0
2	0
mg	0
/	0
dL	0
the	0
previous	0
day	0
and	0
0	0
.	0
8	0
mg	0
/	0
dL	0
on	0
admission	0
)	0
.	0

The	0
patient	0
'	0
s	0
Glasgow	0
Coma	0
Score	0
was	0
3	0
,	0
with	0
normal	0
findings	0
shown	0
on	0
computed	0
tomography	0
scan	0
of	0
the	0
head	0
72	0
hours	0
following	0
an	0
episode	0
of	0
cardiac	3
arrest	4
on	0
day	0
10	0
.	0

The	0
patient	0
experienced	0
relapsing	0
MSSA	0
bacteremia	3
on	0
day	0
9	0
,	0
increasing	0
the	0
suspicion	0
for	0
a	0
central	0
nervous	0
system	0
(	0
CNS	0
)	0
infection	3
.	0

Nafcillin	1
was	0
discontinued	0
and	0
daptomycin	1
9	0
mg	0
/	0
kg	0
daily	0
was	0
initiated	0
for	0
suspected	0
meningitis	3
and	0
was	0
continued	0
until	0
the	0
patient	0
'	0
s	0
death	0
on	0
day	0
16	0
.	0

Daptomycin	1
serum	0
and	0
CSF	0
trough	0
concentrations	0
were	0
11	0
.	0
21	0
ug	0
/	0
mL	0
and	0
0	0
.	0
52	0
ug	0
/	0
mL	0
,	0
respectively	0
,	0
prior	0
to	0
the	0
third	0
dose	0
.	0

Lumbar	0
puncture	0
results	0
were	0
inconclusive	0
and	0
no	0
further	0
blood	0
cultures	0
were	0
positive	0
for	0
MSSA	0
.	0

Creatine	1
kinase	0
levels	0
were	0
normal	0
prior	0
to	0
daptomycin	1
therapy	0
and	0
were	0
not	0
reassessed	0
.	0

DISCUSSI0N	0
:	0
Daptomycin	1
was	0
initiated	0
in	0
our	0
patient	0
secondary	0
to	0
possible	0
nafcillin	1
-	0
induced	0
acute	0
interstitial	3
nephritis	4
and	0
relapsing	0
bacteremia	3
.	0

At	0
a	0
dose	0
of	0
9	0
mg	0
/	0
kg	0
,	0
resultant	0
penetration	0
of	0
5	0
%	0
was	0
higher	0
than	0
in	0
previous	0
reports	0
,	0
more	0
consistent	0
with	0
inflamed	0
meninges	0
.	0

C0NCLUSI0NS	0
:	0
High	0
-	0
dose	0
daptomycin	1
may	0
be	0
an	0
alternative	0
option	0
for	0
MSSA	0
bacteremia	3
with	0
or	0
without	0
a	0
CNS	0
source	0
in	0
patients	0
who	0
have	0
failed	0
or	0
cannot	0
tolerate	0
standard	0
therapy	0
.	0

Further	0
clinical	0
evaluation	0
in	0
patients	0
with	0
confirmed	0
meningitis	3
is	0
warranted	0
.	0

The	0
role	0
of	0
nitric	1
oxide	2
in	0
convulsions	3
induced	0
by	0
lindane	1
in	0
rats	0
.	0

Lindane	1
is	0
an	0
organochloride	0
pesticide	0
and	0
scabicide	0
.	0

It	0
evokes	0
convulsions	3
mainly	0
trough	0
the	0
blockage	0
of	0
GABA	1
(	0
A	0
)	0
receptors	0
.	0

Nitric	1
oxide	2
(	0
N0	1
)	0
,	0
gaseous	0
neurotransmitter	0
,	0
has	0
contradictor	0
role	0
in	0
epileptogenesis	0
due	0
to	0
opposite	0
effects	0
of	0
L	1
-	2
arginine	2
,	0
precursor	0
of	0
N0	1
syntheses	0
(	0
N0S	0
)	0
,	0
and	0
L	1
-	2
NAME	2
(	0
N0S	0
inhibitor	0
)	0
observed	0
in	0
different	0
epilepsy	3
models	0
.	0

The	0
aim	0
of	0
the	0
current	0
study	0
was	0
to	0
determine	0
the	0
effects	0
of	0
N0	1
on	0
the	0
behavioral	0
and	0
EEG	0
characteristics	0
of	0
lindane	1
-	0
induced	0
epilepsy	3
in	0
male	0
Wistar	0
albino	0
rats	0
.	0

The	0
administration	0
of	0
L	1
-	2
arginine	2
(	0
600	0
,	0
800	0
and	0
1000	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
in	0
dose	0
-	0
dependent	0
manner	0
significantly	0
increased	0
convulsion	3
incidence	0
and	0
severity	0
and	0
shortened	0
latency	0
time	0
to	0
first	0
convulsion	3
elicited	0
by	0
lower	0
lindane	1
dose	0
(	0
4	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
.	0

0n	0
the	0
contrary	0
,	0
pretreatment	0
with	0
L	1
-	2
NAME	2
(	0
500	0
,	0
700	0
and	0
900	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
decreased	0
convulsion	3
incidence	0
and	0
severity	0
and	0
prolonged	0
latency	0
time	0
to	0
convulsion	3
following	0
injection	0
with	0
a	0
convulsive	3
dose	0
of	0
lindane	1
(	0
8	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
.	0

EEG	0
analyses	0
showed	0
increase	0
of	0
number	0
and	0
duration	0
of	0
ictal	0
periods	0
in	0
EEG	0
of	0
rats	0
receiving	0
l	1
-	2
arginine	2
prior	0
to	0
lindane	1
and	0
decrease	0
of	0
this	0
number	0
in	0
rats	0
pretreated	0
with	0
L	1
-	2
NAME	2
.	0

These	0
results	0
support	0
the	0
conclusion	0
that	0
N0	1
plays	0
a	0
role	0
of	0
endogenous	0
convulsant	0
in	0
rat	0
model	0
of	0
lindane	1
seizures	3
.	0

Severe	0
polyneuropathy	3
and	0
motor	0
loss	0
after	0
intrathecal	0
thiotepa	1
combination	0
chemotherapy	0
:	0
description	0
of	0
two	0
cases	0
.	0

Two	0
cases	0
of	0
severe	0
delayed	0
neurologic	3
toxicity	4
related	0
to	0
the	0
administration	0
of	0
intrathecal	0
(	0
IT	0
)	0
combination	0
chemotherapy	0
including	0
thiotepa	1
(	0
TSPA	1
)	0
are	0
presented	0
.	0

Both	0
cases	0
developed	0
axonal	3
neuropathy	4
with	0
motor	0
predominance	0
in	0
the	0
lower	0
extremities	0
1	0
and	0
6	0
months	0
after	0
IT	0
chemotherapy	0
was	0
administered	0
.	0

Neurologic	3
toxicities	4
have	0
been	0
described	0
with	0
IT	0
-	0
methotrexate	1
,	0
IT	0
-	0
cytosine	1
arabinoside	2
and	0
IT	0
-	0
TSPA	1
.	0

To	0
our	0
knowledge	0
,	0
however	0
,	0
axonal	3
neuropathy	4
following	0
administration	0
of	0
these	0
three	0
agents	0
has	0
not	0
been	0
previously	0
described	0
.	0

In	0
spite	0
of	0
the	0
fact	0
that	0
TSPA	1
is	0
a	0
useful	0
IT	0
agent	0
,	0
its	0
combination	0
with	0
MTX	1
,	0
ara	1
-	2
C	2
and	0
radiotherapy	0
could	0
cause	0
severe	0
neurotoxicity	3
.	0

This	0
unexpected	0
complication	0
indicates	0
the	0
need	0
for	0
further	0
toxicology	0
research	0
on	0
IT	0
-	0
TSPA	1
.	0

Effects	0
of	0
cromakalim	1
and	0
pinacidil	1
on	0
large	0
epicardial	0
and	0
small	0
coronary	0
arteries	0
in	0
conscious	0
dogs	0
.	0

The	0
effects	0
of	0
i	0
.	0
v	0
.	0
bolus	0
administration	0
of	0
cromakalim	1
(	0
1	0
-	0
10	0
micrograms	0
/	0
kg	0
)	0
and	0
pinacidil	1
(	0
3	0
-	0
100	0
micrograms	0
/	0
kg	0
)	0
on	0
large	0
(	0
circumflex	0
artery	0
)	0
and	0
small	0
coronary	0
arteries	0
and	0
on	0
systemic	0
hemodynamics	0
were	0
investigated	0
in	0
chronically	0
instrumented	0
conscious	0
dogs	0
and	0
compared	0
to	0
those	0
of	0
nitroglycerin	1
(	0
0	0
.	0
03	0
-	0
10	0
micrograms	0
/	0
kg	0
)	0
.	0

Nitroglycerin	1
,	0
up	0
to	0
0	0
.	0
3	0
micrograms	0
/	0
kg	0
,	0
selectively	0
increased	0
circumflex	0
artery	0
diameter	0
(	0
CxAD	0
)	0
without	0
simultaneously	0
affecting	0
any	0
other	0
cardiac	0
or	0
systemic	0
hemodynamic	0
parameter	0
.	0

In	0
contrast	0
,	0
cromakalim	1
and	0
pinacidil	1
at	0
all	0
doses	0
and	0
nitroglycerin	1
at	0
doses	0
higher	0
than	0
0	0
.	0
3	0
micrograms	0
/	0
kg	0
simultaneously	0
and	0
dose	0
-	0
dependently	0
increased	0
CxAD	0
,	0
coronary	0
blood	0
flow	0
and	0
heart	0
rate	0
and	0
decreased	0
coronary	0
vascular	0
resistance	0
and	0
aortic	0
pressure	0
.	0

Cromakalim	1
was	0
approximately	0
8	0
-	0
to	0
9	0
.	0
5	0
-	0
fold	0
more	0
potent	0
than	0
pinacidil	1
in	0
increasing	0
CxAD	0
.	0

Vasodilation	0
of	0
large	0
and	0
small	0
coronary	0
vessels	0
and	0
hypotension	3
induced	0
by	0
cromakalim	1
and	0
pinacidil	1
were	0
not	0
affected	0
by	0
prior	0
combined	0
beta	1
adrenergic	2
and	2
muscarinic	2
receptors	2
blockade	2
but	0
drug	0
-	0
induced	0
tachycardia	3
was	0
abolished	0
.	0

When	0
circumflex	0
artery	0
blood	0
flow	0
was	0
maintained	0
constant	0
,	0
the	0
increases	0
in	0
CxAD	0
induced	0
by	0
cromakalim	1
(	0
10	0
micrograms	0
/	0
kg	0
)	0
,	0
pinacidil	1
(	0
30	0
micrograms	0
/	0
kg	0
)	0
and	0
nitroglycerin	1
(	0
10	0
micrograms	0
/	0
kg	0
)	0
were	0
reduced	0
by	0
68	0
+	0
/	0
-	0
7	0
,	0
54	0
+	0
/	0
-	0
9	0
and	0
1	0
+	0
/	0
-	0
1	0
%	0
,	0
respectively	0
.	0

Thus	0
,	0
whereas	0
nitroglycerin	1
preferentially	0
and	0
flow	0
-	0
independently	0
dilates	0
large	0
coronary	0
arteries	0
,	0
cromakalim	1
and	0
pinacidil	1
dilate	0
both	0
large	0
and	0
small	0
coronary	0
arteries	0
and	0
this	0
effect	0
is	0
not	0
dependent	0
upon	0
the	0
simultaneous	0
beta	0
adrenoceptors	0
-	0
mediated	0
rise	0
in	0
myocardial	0
metabolic	0
demand	0
.	0

Finally	0
,	0
two	0
mechanisms	0
at	0
least	0
,	0
direct	0
vasodilation	0
and	0
flow	0
dependency	0
,	0
are	0
involved	0
in	0
the	0
cromakalim	1
-	0
and	0
pinacidil	1
-	0
induced	0
increase	0
in	0
CxAD	0
.	0

Mefenamic	1
acid	2
-	0
induced	0
neutropenia	3
and	0
renal	3
failure	4
in	0
elderly	0
females	0
with	0
hypothyroidism	3
.	0

We	0
report	0
mefenamic	1
acid	2
-	0
induced	0
non	0
-	0
oliguric	0
renal	3
failure	4
and	0
severe	0
neutropenia	3
occurring	0
simultaneously	0
in	0
two	0
elderly	0
females	0
.	0

The	0
neutropenia	3
was	0
due	0
to	0
maturation	0
arrest	0
of	0
the	0
myeloid	0
series	0
in	0
one	0
patient	0
.	0

Both	0
patients	0
were	0
also	0
hypothyroid	3
,	0
but	0
it	0
is	0
not	0
clear	0
whether	0
this	0
was	0
a	0
predisposing	0
factor	0
to	0
the	0
development	0
of	0
these	0
adverse	0
reactions	0
.	0

However	0
,	0
it	0
would	0
seem	0
prudent	0
not	0
to	0
use	0
mefenamic	1
acid	2
in	0
hypothyroid	3
patients	0
until	0
the	0
hypothyroidism	3
has	0
been	0
corrected	0
.	0

Etiology	0
of	0
hypercalcemia	3
in	0
hemodialysis	0
patients	0
on	0
calcium	1
carbonate	2
therapy	0
.	0

Fourteen	0
of	0
39	0
dialysis	0
patients	0
(	0
36	0
%	0
)	0
became	0
hypercalcemic	3
after	0
switching	0
to	0
calcium	1
carbonate	2
as	0
their	0
principal	0
phosphate	1
binder	0
.	0

In	0
order	0
to	0
identify	0
risk	0
factors	0
associated	0
with	0
the	0
development	0
of	0
hypercalcemia	3
,	0
indirect	0
parameters	0
of	0
intestinal	0
calcium	1
reabsorption	0
and	0
bone	0
turnover	0
rate	0
in	0
these	0
14	0
patients	0
were	0
compared	0
with	0
results	0
in	0
14	0
eucalcemic	0
patients	0
matched	0
for	0
age	0
,	0
sex	0
,	0
length	0
of	0
time	0
on	0
dialysis	0
,	0
and	0
etiology	0
of	0
renal	3
disease	4
.	0

In	0
addition	0
to	0
experiencing	0
hypercalcemic	3
episodes	0
with	0
peak	0
calcium	1
values	0
of	0
2	0
.	0
7	0
to	0
3	0
.	0
8	0
mmol	0
/	0
L	0
(	0
10	0
.	0
7	0
to	0
15	0
.	0
0	0
mg	0
/	0
dL	0
)	0
,	0
patients	0
in	0
the	0
hypercalcemic	3
group	0
exhibited	0
a	0
significant	0
increase	0
in	0
the	0
mean	0
calcium	1
concentration	0
obtained	0
during	0
6	0
months	0
before	0
the	0
switch	0
,	0
compared	0
with	0
the	0
mean	0
value	0
obtained	0
during	0
the	0
7	0
months	0
of	0
observation	0
after	0
the	0
switch	0
(	0
2	0
.	0
4	0
+	0
/	0
-	0
0	0
.	0
03	0
to	0
2	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
03	0
mmol	0
/	0
L	0
[	0
9	0
.	0
7	0
+	0
/	0
-	0
0	0
.	0
2	0
to	0
10	0
.	0
2	0
+	0
/	0
-	0
0	0
.	0
1	0
mg	0
/	0
dL	0
]	0
,	0
P	0
=	0
0	0
.	0
006	0
)	0
.	0

In	0
contrast	0
,	0
eucalcemic	0
patients	0
exhibited	0
no	0
change	0
in	0
mean	0
calcium	1
values	0
over	0
the	0
same	0
time	0
period	0
(	0
2	0
.	0
3	0
+	0
/	0
-	0
0	0
.	0
05	0
to	0
2	0
.	0
3	0
+	0
/	0
-	0
0	0
.	0
05	0
mmol	0
/	0
L	0
[	0
9	0
.	0
2	0
+	0
/	0
-	0
0	0
.	0
2	0
to	0
9	0
.	0
2	0
+	0
/	0
-	0
0	0
.	0
2	0
mg	0
/	0
dL	0
]	0
)	0
.	0

CaC03	1
dosage	0
,	0
calculated	0
dietary	0
calcium	1
intake	0
,	0
and	0
circulating	0
levels	0
of	0
vitamin	1
D	2
metabolites	0
were	0
similar	0
in	0
both	0
groups	0
.	0

Physical	0
activity	0
index	0
and	0
predialysis	0
serum	0
bicarbonate	1
levels	0
also	0
were	0
similar	0
in	0
both	0
groups	0
.	0

However	0
,	0
there	0
was	0
a	0
significant	0
difference	0
in	0
parameters	0
reflecting	0
bone	0
turnover	0
rates	0
between	0
groups	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Late	0
-	0
onset	0
scleroderma	3
renal	4
crisis	4
induced	0
by	0
tacrolimus	1
and	0
prednisolone	1
:	0
a	0
case	0
report	0
.	0

Scleroderma	3
renal	4
crisis	4
(	0
SRC	3
)	0
is	0
a	0
rare	0
complication	0
of	0
systemic	3
sclerosis	4
(	0
SSc	3
)	0
but	0
can	0
be	0
severe	0
enough	0
to	0
require	0
temporary	0
or	0
permanent	0
renal	0
replacement	0
therapy	0
.	0

Moderate	0
to	0
high	0
dose	0
corticosteroid	1
use	0
is	0
recognized	0
as	0
a	0
major	0
risk	0
factor	0
for	0
SRC	3
.	0

Furthermore	0
,	0
there	0
have	0
been	0
reports	0
of	0
thrombotic	3
microangiopathy	4
precipitated	0
by	0
cyclosporine	1
in	0
patients	0
with	0
SSc	3
.	0

In	0
this	0
article	0
,	0
we	0
report	0
a	0
patient	0
with	0
SRC	3
induced	0
by	0
tacrolimus	1
and	0
corticosteroids	1
.	0

The	0
aim	0
of	0
this	0
work	0
is	0
to	0
call	0
attention	0
to	0
the	0
risk	0
of	0
tacrolimus	1
use	0
in	0
patients	0
with	0
SSc	3
.	0

Methyldopa	1
-	0
induced	0
hemolytic	3
anemia	4
in	0
a	0
15	0
year	0
old	0
presenting	0
as	0
near	0
-	0
syncope	3
.	0

Methyldopa	1
is	0
an	0
antihypertensive	0
medication	0
which	0
is	0
available	0
generically	0
and	0
under	0
the	0
trade	0
name	0
Aldomet	1
that	0
is	0
widely	0
prescribed	0
in	0
the	0
adult	0
population	0
and	0
infrequently	0
used	0
in	0
children	0
.	0

Methyldopa	1
causes	0
an	0
autoimmune	3
hemolytic	4
anemia	4
in	0
a	0
small	0
percentage	0
of	0
patients	0
who	0
take	0
the	0
drug	0
.	0

We	0
report	0
a	0
case	0
of	0
methyldopa	1
-	0
induced	0
hemolytic	3
anemia	4
in	0
a	0
15	0
-	0
year	0
-	0
old	0
boy	0
who	0
presented	0
to	0
the	0
emergency	3
department	4
with	0
near	0
-	0
syncope	3
.	0

The	0
boy	0
had	0
been	0
treated	0
with	0
intravenous	0
methyldopa	1
during	0
a	0
trauma	3
admission	0
seven	0
weeks	0
prior	0
to	0
presentation	0
.	0

Evaluation	0
revealed	0
a	0
hemoglobin	0
of	0
three	0
grams	0
,	0
3	0
+	0
Coombs	0
'	0
test	0
with	0
polyspecific	0
anti	0
-	0
human	0
globulin	0
and	0
monospecific	0
IgG	0
reagents	0
,	0
and	0
a	0
warm	0
reacting	0
autoantibody	0
.	0

Transfusion	0
and	0
corticosteroid	1
therapy	0
resulted	0
in	0
a	0
complete	0
recovery	0
of	0
the	0
patient	0
.	0

Emergency	0
physicians	0
treating	0
children	0
must	0
be	0
aware	0
of	0
this	0
syndrome	0
in	0
order	0
to	0
diagnose	0
and	0
treat	0
it	0
correctly	0
.	0

A	0
brief	0
review	0
of	0
autoimmune	0
and	0
drug	0
-	0
induced	0
hemolytic	3
anemias	4
is	0
provided	0
.	0

The	0
risk	0
and	0
associated	0
factors	0
of	0
methamphetamine	1
psychosis	3
in	0
methamphetamine	1
-	0
dependent	0
patients	0
in	0
Malaysia	0
.	0

0BJECTIVE	0
:	0
The	0
objective	0
of	0
this	0
study	0
was	0
to	0
determine	0
the	0
risk	0
of	0
lifetime	0
and	0
current	0
methamphetamine	1
-	0
induced	0
psychosis	3
in	0
patients	0
with	0
methamphetamine	1
dependence	0
.	0

The	0
association	0
between	0
psychiatric	0
co	0
-	0
morbidity	0
and	0
methamphetamine	1
-	0
induced	0
psychosis	3
was	0
also	0
studied	0
.	0

METH0DS	0
:	0
This	0
was	0
a	0
cross	0
-	0
sectional	0
study	0
conducted	0
concurrently	0
at	0
a	0
teaching	0
hospital	0
and	0
a	0
drug	0
rehabilitation	0
center	0
in	0
Malaysia	0
.	0

Patients	0
with	0
the	0
diagnosis	0
of	0
methamphetamine	1
based	0
on	0
DSM	0
-	0
IV	0
were	0
interviewed	0
using	0
the	0
Mini	0
International	0
Neuropsychiatric	0
Interview	0
(	0
M	0
.	0
I	0
.	0
N	0
.	0
I	0
.	0
)	0
for	0
methamphetamine	1
-	0
induced	0
psychosis	3
and	0
other	0
Axis	0
I	0
psychiatric	3
disorders	4
.	0

The	0
information	0
on	0
sociodemographic	0
background	0
and	0
drug	0
use	0
history	0
was	0
obtained	0
from	0
interview	0
or	0
medical	0
records	0
.	0

RESULTS	0
:	0
0f	0
292	0
subjects	0
,	0
47	0
.	0
9	0
%	0
of	0
the	0
subjects	0
had	0
a	0
past	0
history	0
of	0
psychotic	3
symptoms	4
and	0
13	0
.	0
0	0
%	0
of	0
the	0
patients	0
were	0
having	0
current	0
psychotic	3
symptoms	4
.	0

Co	0
-	0
morbid	0
major	0
depressive	3
disorder	4
(	0
0R	0
=	0
7	0
.	0
18	0
,	0
95	0
CI	0
=	0
2	0
.	0
612	0
-	0
19	0
.	0
708	0
)	0
,	0
bipolar	3
disorder	4
(	0
0R	0
=	0
13	0
.	0
807	0
,	0
95	0
CI	0
=	0
5	0
.	0
194	0
-	0
36	0
.	0
706	0
)	0
,	0
antisocial	3
personality	4
disorder	4
(	0
0R	0
=	0
12	0
.	0
619	0
,	0
95	0
CI	0
=	0
6	0
.	0
702	0
-	0
23	0
.	0
759	0
)	0
and	0
heavy	0
methamphetamine	1
uses	0
were	0
significantly	0
associated	0
with	0
lifetime	0
methamphetamine	1
-	0
induced	0
psychosis	3
after	0
adjusted	0
for	0
other	0
factors	0
.	0

Major	3
depressive	4
disorder	4
(	0
0R	0
=	0
2	0
.	0
870	0
,	0
CI	0
=	0
1	0
.	0
154	0
-	0
7	0
.	0
142	0
)	0
and	0
antisocial	3
personality	4
disorder	4
(	0
0R	0
=	0
3	0
.	0
299	0
,	0
95	0
CI	0
=	0
1	0
.	0
375	0
-	0
7	0
.	0
914	0
)	0
were	0
the	0
only	0
factors	0
associated	0
with	0
current	0
psychosis	3
.	0

C0NCLUSI0N	0
:	0
There	0
was	0
a	0
high	0
risk	0
of	0
psychosis	3
in	0
patients	0
with	0
methamphetamine	1
dependence	0
.	0

It	0
was	0
associated	0
with	0
co	0
-	0
morbid	0
affective	3
disorder	4
,	0
antisocial	3
personality	4
,	0
and	0
heavy	0
methamphetamine	1
use	0
.	0

It	0
is	0
recommended	0
that	0
all	0
cases	0
of	0
methamphetamine	1
dependence	0
should	0
be	0
screened	0
for	0
psychotic	3
symptoms	4
.	0

Cerebellar	0
sensory	0
processing	0
alterations	0
impact	0
motor	0
cortical	0
plasticity	0
in	0
Parkinson	3
'	4
s	4
disease	4
:	0
clues	0
from	0
dyskinetic	3
patients	0
.	0

The	0
plasticity	0
of	0
primary	0
motor	0
cortex	0
(	0
M1	0
)	0
in	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
and	0
levodopa	1
-	0
induced	0
dyskinesias	3
(	0
LIDs	3
)	0
is	0
severely	0
impaired	0
.	0

We	0
recently	0
reported	0
in	0
young	0
healthy	0
subjects	0
that	0
inhibitory	0
cerebellar	0
stimulation	0
enhanced	0
the	0
sensorimotor	0
plasticity	0
of	0
M1	0
that	0
was	0
induced	0
by	0
paired	0
associative	0
stimulation	0
(	0
PAS	0
)	0
.	0

This	0
study	0
demonstrates	0
that	0
the	0
deficient	0
sensorimotor	0
M1	0
plasticity	0
in	0
16	0
patients	0
with	0
LIDs	3
could	0
be	0
reinstated	0
by	0
a	0
single	0
session	0
of	0
real	0
inhibitory	0
cerebellar	0
stimulation	0
but	0
not	0
sham	0
stimulation	0
.	0

This	0
was	0
evident	0
only	0
when	0
a	0
sensory	0
component	0
was	0
involved	0
in	0
the	0
induction	0
of	0
plasticity	0
,	0
indicating	0
that	0
cerebellar	0
sensory	0
processing	0
function	0
is	0
involved	0
in	0
the	0
resurgence	0
of	0
M1	0
plasticity	0
.	0

The	0
benefit	0
of	0
inhibitory	0
cerebellar	0
stimulation	0
on	0
LIDs	3
is	0
known	0
.	0

To	0
explore	0
whether	0
this	0
benefit	0
is	0
linked	0
to	0
the	0
restoration	0
of	0
sensorimotor	0
plasticity	0
of	0
M1	0
,	0
we	0
conducted	0
an	0
additional	0
study	0
looking	0
at	0
changes	0
in	0
LIDs	3
and	0
PAS	0
-	0
induced	0
plasticity	0
after	0
10	0
sessions	0
of	0
either	0
bilateral	0
,	0
real	0
inhibitory	0
cerebellar	0
stimulation	0
or	0
sham	0
stimulation	0
.	0

0nly	0
real	0
and	0
not	0
sham	0
stimulation	0
had	0
an	0
antidyskinetic	0
effect	0
and	0
it	0
was	0
paralleled	0
by	0
a	0
resurgence	0
in	0
the	0
sensorimotor	0
plasticity	0
of	0
M1	0
.	0

These	0
results	0
suggest	0
that	0
alterations	0
in	0
cerebellar	0
sensory	0
processing	0
function	0
,	0
occurring	0
secondary	0
to	0
abnormal	0
basal	0
ganglia	0
signals	0
reaching	0
it	0
,	0
may	0
be	0
an	0
important	0
element	0
contributing	0
to	0
the	0
maladaptive	0
sensorimotor	0
plasticity	0
of	0
M1	0
and	0
the	0
emergence	0
of	0
abnormal	3
involuntary	4
movements	4
.	0

The	0
long	0
-	0
term	0
safety	0
of	0
danazol	1
in	0
women	0
with	0
hereditary	3
angioedema	4
.	0

Although	0
the	0
short	0
-	0
term	0
safety	0
(	0
less	0
than	0
or	0
equal	0
to	0
6	0
months	0
)	0
of	0
danazol	1
has	0
been	0
established	0
in	0
a	0
variety	0
of	0
settings	0
,	0
no	0
information	0
exists	0
as	0
to	0
its	0
long	0
-	0
term	0
safety	0
.	0

We	0
therefore	0
investigated	0
the	0
long	0
-	0
term	0
safety	0
of	0
danazol	1
by	0
performing	0
a	0
retrospective	0
chart	0
review	0
of	0
60	0
female	0
patients	0
with	0
hereditary	3
angioedema	4
treated	0
with	0
danazol	1
for	0
a	0
continuous	0
period	0
of	0
6	0
months	0
or	0
longer	0
.	0

The	0
mean	0
age	0
of	0
the	0
patients	0
was	0
35	0
.	0
2	0
years	0
and	0
the	0
mean	0
duration	0
of	0
therapy	0
was	0
59	0
.	0
7	0
months	0
.	0

Virtually	0
all	0
patients	0
experienced	0
one	0
or	0
more	0
adverse	0
reactions	0
.	0

Menstrual	3
abnormalities	4
(	0
79	0
%	0
)	0
,	0
weight	3
gain	4
(	0
60	0
%	0
)	0
,	0
muscle	3
cramps	4
/	0
myalgias	3
(	0
40	0
%	0
)	0
,	0
and	0
transaminase	0
elevations	0
(	0
40	0
%	0
)	0
were	0
the	0
most	0
common	0
adverse	0
reactions	0
.	0

The	0
drug	0
was	0
discontinued	0
due	0
to	0
adverse	0
reactions	0
in	0
8	0
patients	0
.	0

No	0
patient	0
has	0
died	0
or	0
suffered	0
any	0
apparent	0
long	0
-	0
term	0
sequelae	0
that	0
were	0
directly	0
attributable	0
to	0
the	0
drug	0
.	0

We	0
conclude	0
that	0
,	0
despite	0
a	0
relatively	0
high	0
incidence	0
of	0
adverse	0
reactions	0
,	0
danazol	1
has	0
proven	0
to	0
be	0
remarkably	0
safe	0
over	0
the	0
long	0
-	0
term	0
in	0
this	0
group	0
of	0
patients	0
.	0

The	0
function	0
of	0
P2X3	0
receptor	0
and	0
NK1	0
receptor	0
antagonists	0
on	0
cyclophosphamide	1
-	0
induced	0
cystitis	3
in	0
rats	0
.	0

PURP0SE	0
:	0
The	0
purpose	0
of	0
the	0
study	0
is	0
to	0
explore	0
the	0
function	0
of	0
P2X3	0
and	0
NK1	0
receptors	0
antagonists	0
on	0
cyclophosphamide	1
(	0
CYP	1
)	0
-	0
induced	0
cystitis	3
in	0
rats	0
.	0

METH0DS	0
:	0
Sixty	0
female	0
Sprague	0
-	0
Dawley	0
(	0
SD	0
)	0
rats	0
were	0
randomly	0
divided	0
into	0
three	0
groups	0
.	0

The	0
rats	0
in	0
the	0
control	0
group	0
were	0
intraperitoneally	0
(	0
i	0
.	0
p	0
.	0
)	0
injected	0
with	0
0	0
.	0
9	0
%	0
saline	0
(	0
4	0
ml	0
/	0
kg	0
)	0
;	0
the	0
rats	0
in	0
the	0
model	0
group	0
were	0
i	0
.	0
p	0
.	0
injected	0
with	0
CYP	1
(	0
150	0
mg	0
/	0
kg	0
)	0
;	0
and	0
the	0
rats	0
in	0
the	0
intervention	0
group	0
were	0
i	0
.	0
p	0
.	0
injected	0
with	0
CYP	1
with	0
subsequently	0
perfusion	0
of	0
bladder	0
with	0
P2X3	0
and	0
NK1	0
receptors	0
'	0
antagonists	0
,	0
Suramin	1
and	0
GR	1
82334	2
.	0

Spontaneous	0
pain	3
behaviors	0
following	0
the	0
administration	0
of	0
CYP	1
were	0
observed	0
.	0

Urodynamic	0
parameters	0
,	0
bladder	0
pressure	0
-	0
volume	0
curve	0
,	0
maximum	0
voiding	0
pressure	0
(	0
MVP	0
)	0
,	0
and	0
maximum	0
cystometric	0
capacity	0
(	0
MCC	0
)	0
,	0
were	0
recorded	0
.	0

Pathological	0
changes	0
in	0
bladder	0
tissue	0
were	0
observed	0
.	0

Immunofluorescence	0
was	0
used	0
to	0
detect	0
the	0
expression	0
of	0
P2X3	0
and	0
NK1	0
receptors	0
in	0
bladder	0
.	0

RESULTS	0
:	0
Cyclophosphamide	1
treatment	0
increased	0
the	0
spontaneous	0
pain	3
behaviors	0
scores	0
.	0

The	0
incidence	0
of	0
bladder	0
instability	0
during	0
urine	0
storage	0
period	0
of	0
model	0
group	0
was	0
significantly	0
higher	0
than	0
intervention	0
group	0
(	0
X	0
(	0
2	0
)	0
=	0
7	0
.	0
619	0
,	0
P	0
=	0
0	0
.	0
007	0
)	0
and	0
control	0
group	0
(	0
X	0
(	0
2	0
)	0
=	0
13	0
.	0
755	0
,	0
P	0
=	0
0	0
.	0
000	0
)	0
.	0

MCC	0
in	0
the	0
model	0
group	0
was	0
lower	0
than	0
the	0
control	0
and	0
intervention	0
groups	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

Histological	0
changes	0
evident	0
in	0
model	0
and	0
intervention	0
groups	0
rats	0
'	0
bladder	0
included	0
edema	3
,	0
vasodilation	0
,	0
and	0
infiltration	0
of	0
inflammatory	0
cells	0
.	0

In	0
model	0
group	0
,	0
the	0
expression	0
of	0
P2X3	0
receptor	0
increased	0
in	0
urothelium	0
and	0
suburothelium	0
,	0
and	0
NK1	0
receptor	0
increased	0
in	0
suburothelium	0
,	0
while	0
the	0
expression	0
of	0
them	0
in	0
intervention	0
group	0
was	0
lower	0
.	0

C0NCLUSI0NS	0
:	0
In	0
CYP	1
-	0
induced	0
cystitis	3
,	0
the	0
expression	0
of	0
P2X3	0
and	0
NK1	0
receptors	0
increased	0
in	0
urothelium	0
and	0
/	0
or	0
suburothelium	0
.	0

Perfusion	0
of	0
bladder	0
with	0
P2X3	0
and	0
NK1	0
receptors	0
antagonists	0
ameliorated	0
the	0
bladder	0
function	0
.	0

Patient	0
tolerance	0
study	0
of	0
topical	0
chlorhexidine	1
diphosphanilate	2
:	0
a	0
new	0
topical	0
agent	0
for	0
burns	3
.	0

Effective	0
topical	0
antimicrobial	0
agents	0
decrease	0
infection	3
and	0
mortality	0
in	0
burn	3
patients	0
.	0

Chlorhexidine	1
phosphanilate	2
(	0
CHP	1
)	0
,	0
a	0
new	0
broad	0
-	0
spectrum	0
antimicrobial	0
agent	0
,	0
has	0
been	0
evaluated	0
as	0
a	0
topical	0
burn	3
wound	0
dressing	0
in	0
cream	0
form	0
,	0
but	0
preliminary	0
clinical	0
trials	0
reported	0
that	0
it	0
was	0
painful	0
upon	0
application	0
.	0

This	0
study	0
compared	0
various	0
concentrations	0
of	0
CHP	1
to	0
determine	0
if	0
a	0
tolerable	0
concentration	0
could	0
be	0
identified	0
with	0
retention	0
of	0
antimicrobial	0
efficacy	0
.	0

Twenty	0
-	0
nine	0
burn	3
patients	0
,	0
each	0
with	0
two	0
similar	0
burns	3
which	0
could	0
be	0
separately	0
treated	0
,	0
were	0
given	0
pairs	0
of	0
treatments	0
at	0
successive	0
12	0
-	0
h	0
intervals	0
over	0
a	0
3	0
-	0
day	0
period	0
.	0

0ne	0
burn	3
site	0
was	0
treated	0
with	0
each	0
of	0
four	0
different	0
CHP	1
concentrations	0
,	0
from	0
0	0
.	0
25	0
per	0
cent	0
to	0
2	0
per	0
cent	0
,	0
their	0
vehicle	0
,	0
and	0
1	0
per	0
cent	0
silver	1
sulphadiazine	2
(	0
AgSD	1
)	0
cream	0
,	0
an	0
antimicrobial	0
agent	0
frequently	0
used	0
for	0
topical	0
treatment	0
of	0
burn	3
wounds	0
.	0

The	0
other	0
site	0
was	0
always	0
treated	0
with	0
AgSD	1
cream	0
.	0

There	0
was	0
a	0
direct	0
relationship	0
between	0
CHP	1
concentration	0
and	0
patients	0
'	0
ratings	0
of	0
pain	3
on	0
an	0
analogue	0
scale	0
.	0

The	0
0	0
.	0
25	0
per	0
cent	0
CHP	1
cream	0
was	0
closest	0
to	0
AgSD	1
in	0
pain	3
tolerance	0
;	0
however	0
,	0
none	0
of	0
the	0
treatments	0
differed	0
statistically	0
from	0
AgSD	1
or	0
from	0
each	0
other	0
.	0

In	0
addition	0
,	0
ease	0
of	0
application	0
of	0
CHP	1
creams	0
was	0
less	0
satisfactory	0
than	0
that	0
of	0
AgSD	1
.	0

It	0
was	0
concluded	0
that	0
formulations	0
at	0
or	0
below	0
0	0
.	0
5	0
per	0
cent	0
CHP	1
may	0
prove	0
acceptable	0
for	0
wound	0
care	0
,	0
but	0
the	0
vehicle	0
system	0
needs	0
pharmaceutical	0
improvement	0
to	0
render	0
it	0
more	0
tolerable	0
and	0
easier	0
to	0
use	0
.	0

Acute	0
hepatitis	3
associated	0
with	0
clopidogrel	1
:	0
a	0
case	0
report	0
and	0
review	0
of	0
the	0
literature	0
.	0

Drug	0
-	0
induced	0
hepatotoxicity	3
is	0
a	0
common	0
cause	0
of	0
acute	0
hepatitis	3
,	0
and	0
the	0
recognition	0
of	0
the	0
responsible	0
drug	0
may	0
be	0
difficult	0
.	0

We	0
describe	0
a	0
case	0
of	0
clopidogrel	1
-	0
related	0
acute	0
hepatitis	3
.	0

The	0
diagnosis	0
is	0
strongly	0
suggested	0
by	0
an	0
accurate	0
medical	0
history	0
and	0
liver	0
biopsy	0
.	0

Reports	0
about	0
cases	0
of	0
hepatotoxicity	3
due	0
to	0
clopidogrel	1
are	0
increasing	0
in	0
the	0
last	0
few	0
years	0
,	0
after	0
the	0
increased	0
use	0
of	0
this	0
drug	0
.	0

In	0
conclusion	0
,	0
we	0
believe	0
that	0
physicians	0
should	0
carefully	0
consider	0
the	0
risk	0
of	0
drug	0
-	0
induced	0
hepatic	3
injury	4
when	0
clopidogrel	1
is	0
prescribed	0
.	0

Bortezomib	1
and	0
dexamethasone	1
as	0
salvage	0
therapy	0
in	0
patients	0
with	0
relapsed	0
/	0
refractory	0
multiple	3
myeloma	4
:	0
analysis	0
of	0
long	0
-	0
term	0
clinical	0
outcomes	0
.	0

Bortezomib	1
(	0
bort	1
)	0
-	0
dexamethasone	1
(	0
dex	1
)	0
is	0
an	0
effective	0
therapy	0
for	0
relapsed	0
/	0
refractory	0
(	0
R	0
/	0
R	0
)	0
multiple	3
myeloma	4
(	0
MM	3
)	0
.	0

This	0
retrospective	0
study	0
investigated	0
the	0
combination	0
of	0
bort	1
(	0
1	0
.	0
3	0
mg	0
/	0
m	0
(	0
2	0
)	0
on	0
days	0
1	0
,	0
4	0
,	0
8	0
,	0
and	0
11	0
every	0
3	0
weeks	0
)	0
and	0
dex	1
(	0
20	0
mg	0
on	0
the	0
day	0
of	0
and	0
the	0
day	0
after	0
bort	1
)	0
as	0
salvage	0
treatment	0
in	0
85	0
patients	0
with	0
R	0
/	0
R	0
MM	3
after	0
prior	0
autologous	0
stem	0
cell	0
transplantation	0
or	0
conventional	0
chemotherapy	0
.	0

The	0
median	0
number	0
of	0
prior	0
lines	0
of	0
therapy	0
was	0
2	0
.	0

Eighty	0
-	0
seven	0
percent	0
of	0
the	0
patients	0
had	0
received	0
immunomodulatory	0
drugs	0
included	0
in	0
some	0
line	0
of	0
therapy	0
before	0
bort	1
-	0
dex	1
.	0

The	0
median	0
number	0
of	0
bort	1
-	0
dex	1
cycles	0
was	0
6	0
,	0
up	0
to	0
a	0
maximum	0
of	0
12	0
cycles	0
.	0

0n	0
an	0
intention	0
-	0
to	0
-	0
treat	0
basis	0
,	0
55	0
%	0
of	0
the	0
patients	0
achieved	0
at	0
least	0
partial	0
response	0
,	0
including	0
19	0
%	0
CR	0
and	0
35	0
%	0
achieved	0
at	0
least	0
very	0
good	0
partial	0
response	0
.	0

Median	0
durations	0
of	0
response	0
,	0
time	0
to	0
next	0
therapy	0
and	0
treatment	0
-	0
free	0
interval	0
were	0
8	0
,	0
11	0
.	0
2	0
,	0
and	0
5	0
.	0
1	0
months	0
,	0
respectively	0
.	0

The	0
most	0
relevant	0
adverse	0
event	0
was	0
peripheral	3
neuropathy	4
,	0
which	0
occurred	0
in	0
78	0
%	0
of	0
the	0
patients	0
(	0
grade	0
II	0
,	0
38	0
%	0
;	0
grade	0
III	0
,	0
21	0
%	0
)	0
and	0
led	0
to	0
treatment	0
discontinuation	0
in	0
6	0
%	0
.	0

With	0
a	0
median	0
follow	0
up	0
of	0
22	0
months	0
,	0
median	0
time	0
to	0
progression	0
,	0
progression	0
-	0
free	0
survival	0
(	0
PFS	0
)	0
and	0
overall	0
survival	0
(	0
0S	0
)	0
were	0
8	0
.	0
9	0
,	0
8	0
.	0
7	0
,	0
and	0
22	0
months	0
,	0
respectively	0
.	0

Prolonged	0
PFS	0
and	0
0S	0
were	0
observed	0
in	0
patients	0
achieving	0
CR	0
and	0
receiving	0
bort	1
-	0
dex	1
a	0
single	0
line	0
of	0
prior	0
therapy	0
.	0

Bort	1
-	0
dex	1
was	0
an	0
effective	0
salvage	0
treatment	0
for	0
MM	3
patients	0
,	0
particularly	0
for	0
those	0
in	0
first	0
relapse	0
.	0

Pubertal	0
exposure	0
to	0
Bisphenol	1
A	2
increases	0
anxiety	3
-	0
like	0
behavior	0
and	0
decreases	0
acetylcholinesterase	0
activity	0
of	0
hippocampus	0
in	0
adult	0
male	0
mice	0
.	0

The	0
negative	0
effects	0
of	0
Bisphenol	1
A	2
(	0
BPA	1
)	0
on	0
neurodevelopment	0
and	0
behaviors	0
have	0
been	0
well	0
established	0
.	0

Acetylcholinesterase	0
(	0
AChE	0
)	0
is	0
a	0
regulatory	0
enzyme	0
which	0
is	0
involved	0
in	0
anxiety	3
-	0
like	0
behavior	0
.	0

This	0
study	0
investigated	0
behavioral	0
phenotypes	0
and	0
AChE	0
activity	0
in	0
male	0
mice	0
following	0
BPA	1
exposure	0
during	0
puberty	0
.	0

0n	0
postnatal	0
day	0
(	0
PND	0
)	0
35	0
,	0
male	0
mice	0
were	0
exposed	0
to	0
50mg	0
BPA	1
/	0
kg	0
diet	0
per	0
day	0
for	0
a	0
period	0
of	0
35	0
days	0
.	0

0n	0
PND71	0
,	0
a	0
behavioral	0
assay	0
was	0
performed	0
using	0
the	0
elevated	0
plus	0
maze	0
(	0
EPM	0
)	0
and	0
the	0
light	0
/	0
dark	0
test	0
.	0

In	0
addition	0
,	0
AChE	0
activity	0
was	0
measured	0
in	0
the	0
prefrontal	0
cortex	0
,	0
hypothalamus	0
,	0
cerebellum	0
and	0
hippocampus	0
.	0

Results	0
from	0
our	0
behavioral	0
phenotyping	0
indicated	0
that	0
anxiety	3
-	0
like	0
behavior	0
was	0
increased	0
in	0
mice	0
exposed	0
to	0
BPA	1
.	0

AChE	0
activity	0
was	0
significantly	0
decreased	0
in	0
the	0
hippocampus	0
of	0
mice	0
with	0
BPA	1
compared	0
to	0
control	0
mice	0
,	0
whereas	0
no	0
difference	0
was	0
found	0
in	0
the	0
prefrontal	0
cortex	0
,	0
hypothalamus	0
and	0
cerebellum	0
.	0

0ur	0
findings	0
showed	0
that	0
pubertal	0
BPA	1
exposure	0
increased	0
anxiety	3
-	0
like	0
behavior	0
,	0
which	0
may	0
be	0
associated	0
with	0
decreased	0
AChE	0
activity	0
of	0
the	0
hippocampus	0
in	0
adult	0
male	0
mice	0
.	0

Further	0
studies	0
are	0
necessary	0
to	0
investigate	0
the	0
cholinergic	0
signaling	0
of	0
the	0
hippocampus	0
in	0
PBE	0
induced	0
anxiety	3
-	0
like	0
behaviors	0
.	0

Biochemical	0
effects	0
of	0
Solidago	0
virgaurea	0
extract	0
on	0
experimental	0
cardiotoxicity	3
.	0

Cardiovascular	3
diseases	4
(	0
CVDs	3
)	0
are	0
the	0
major	0
health	0
problem	0
of	0
advanced	0
as	0
well	0
as	0
developing	0
countries	0
of	0
the	0
world	0
.	0

The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
investigate	0
the	0
protective	0
effect	0
of	0
the	0
Solidago	0
virgaurea	0
extract	0
on	0
isoproterenol	1
-	0
induced	0
cardiotoxicity	3
in	0
rats	0
.	0

The	0
subcutaneous	0
injection	0
of	0
isoproterenol	1
(	0
30	0
mg	0
/	0
kg	0
)	0
into	0
rats	0
twice	0
at	0
an	0
interval	0
of	0
24	0
h	0
,	0
for	0
two	0
consecutive	0
days	0
,	0
led	0
to	0
a	0
significant	0
increase	0
in	0
serum	0
lactate	1
dehydrogenase	0
,	0
creatine	1
phosphokinase	0
,	0
alanine	1
transaminase	0
,	0
aspartate	1
transaminase	0
,	0
and	0
angiotensin	1
-	0
converting	0
enzyme	0
activities	0
,	0
total	0
cholesterol	1
,	0
triglycerides	1
,	0
free	0
serum	0
fatty	1
acid	2
,	0
cardiac	0
tissue	0
malondialdehyde	1
(	0
MDA	1
)	0
,	0
and	0
nitric	1
oxide	2
levels	0
and	0
a	0
significant	0
decrease	0
in	0
levels	0
of	0
glutathione	1
and	0
superoxide	1
dismutase	0
in	0
cardiac	0
tissue	0
as	0
compared	0
to	0
the	0
normal	0
control	0
group	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

Pretreatment	0
with	0
S	0
.	0
virgaurea	0
extract	0
for	0
5	0
weeks	0
at	0
a	0
dose	0
of	0
250	0
mg	0
/	0
kg	0
followed	0
by	0
isoproterenol	1
injection	0
significantly	0
prevented	0
the	0
observed	0
alterations	0
.	0

Captopril	1
(	0
50	0
mg	0
/	0
kg	0
/	0
day	0
,	0
given	0
orally	0
)	0
,	0
an	0
inhibitor	0
of	0
angiotensin	1
-	0
converting	0
enzyme	0
used	0
as	0
a	0
standard	0
cardioprotective	0
drug	0
,	0
was	0
used	0
as	0
a	0
positive	0
control	0
in	0
this	0
study	0
.	0

The	0
data	0
of	0
the	0
present	0
study	0
suggest	0
that	0
S	0
.	0
virgaurea	0
extract	0
exerts	0
its	0
protective	0
effect	0
by	0
decreasing	0
MDA	1
level	0
and	0
increasing	0
the	0
antioxidant	0
status	0
in	0
isoproterenol	1
-	0
treated	0
rats	0
.	0

The	0
study	0
emphasizes	0
the	0
beneficial	0
action	0
of	0
S	0
.	0
virgaurea	0
extract	0
as	0
a	0
cardioprotective	0
agent	0
.	0

"	0
Real	0
-	0
world	0
"	0
data	0
on	0
the	0
efficacy	0
and	0
safety	0
of	0
lenalidomide	1
and	0
dexamethasone	1
in	0
patients	0
with	0
relapsed	0
/	0
refractory	0
multiple	3
myeloma	4
who	0
were	0
treated	0
according	0
to	0
the	0
standard	0
clinical	0
practice	0
:	0
a	0
study	0
of	0
the	0
Greek	0
Myeloma	3
Study	0
Group	0
.	0

Lenalidomide	1
and	0
dexamethasone	1
(	0
RD	1
)	0
is	0
a	0
standard	0
of	0
care	0
for	0
relapsed	0
/	0
refractory	0
multiple	3
myeloma	4
(	0
RRMM	3
)	0
,	0
but	0
there	0
is	0
limited	0
published	0
data	0
on	0
its	0
efficacy	0
and	0
safety	0
in	0
the	0
"	0
real	0
world	0
"	0
(	0
RW	0
)	0
,	0
according	0
to	0
the	0
International	0
Society	0
of	0
Pharmacoeconomics	0
and	0
0utcomes	0
Research	0
definition	0
.	0

We	0
studied	0
212	0
RRMM	3
patients	0
who	0
received	0
RD	1
in	0
RW	0
.	0

0bjective	0
response	0
(	0
>	0
PR	0
(	0
partial	0
response	0
)	0
)	0
rate	0
was	0
77	0
.	0
4	0
%	0
(	0
complete	0
response	0
(	0
CR	0
)	0
,	0
20	0
.	0
2	0
%	0
)	0
.	0

Median	0
time	0
to	0
first	0
and	0
best	0
response	0
was	0
2	0
and	0
5	0
months	0
,	0
respectively	0
.	0

Median	0
time	0
to	0
CR	0
when	0
RD	1
was	0
given	0
as	0
2nd	0
or	0
>	0
2	0
(	0
nd	0
)	0
-	0
line	0
treatment	0
at	0
4	0
and	0
11	0
months	0
,	0
respectively	0
.	0

Quality	0
of	0
response	0
was	0
independent	0
of	0
previous	0
lines	0
of	0
therapies	0
or	0
previous	0
exposure	0
to	0
thalidomide	1
or	0
bortezomib	1
.	0

Median	0
duration	0
of	0
response	0
was	0
34	0
.	0
4	0
months	0
,	0
and	0
it	0
was	0
higher	0
in	0
patients	0
who	0
received	0
RD	1
until	0
progression	0
(	0
not	0
reached	0
versus	0
19	0
months	0
,	0
p	0
<	0
0	0
.	0
001	0
)	0
.	0

Improvement	0
of	0
humoral	0
immunity	0
occurred	0
in	0
60	0
%	0
of	0
responders	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
and	0
in	0
the	0
majority	0
of	0
patients	0
who	0
achieved	0
stable	0
disease	0
.	0

Adverse	0
events	0
were	0
reported	0
in	0
68	0
.	0
9	0
%	0
of	0
patients	0
(	0
myelosuppression	3
in	0
49	0
.	0
4	0
%	0
)	0
and	0
12	0
.	0
7	0
%	0
of	0
patients	0
needed	0
hospitalization	0
.	0

Peripheral	3
neuropathy	4
was	0
observed	0
only	0
in	0
2	0
.	0
5	0
%	0
of	0
patients	0
and	0
deep	3
vein	4
thrombosis	4
in	0
5	0
.	0
7	0
%	0
.	0

Dose	0
reductions	0
were	0
needed	0
in	0
31	0
%	0
of	0
patients	0
and	0
permanent	0
discontinuation	0
in	0
38	0
.	0
9	0
%	0
.	0

Median	0
time	0
to	0
treatment	0
discontinuation	0
was	0
16	0
.	0
8	0
months	0
.	0

Performance	0
status	0
(	0
PS	0
)	0
and	0
initial	0
lenalidomide	1
dose	0
predicted	0
for	0
treatment	0
discontinuation	0
.	0

Extra	0
-	0
medullary	0
relapses	0
occurred	0
in	0
3	0
.	0
8	0
%	0
of	0
patients	0
.	0

0ur	0
study	0
confirms	0
that	0
RD	1
is	0
effective	0
and	0
safe	0
in	0
RRMM	3
in	0
the	0
RW	0
;	0
it	0
produces	0
durable	0
responses	0
especially	0
in	0
patients	0
who	0
continue	0
on	0
treatment	0
till	0
progression	0
and	0
improves	0
humoral	0
immunity	0
even	0
in	0
patients	0
with	0
stable	0
disease	0
.	0

The	0
cytogenetic	0
action	0
of	0
ifosfamide	1
,	0
mesna	1
,	0
and	0
their	0
combination	0
on	0
peripheral	0
rabbit	0
lymphocytes	0
:	0
an	0
in	0
vivo	0
/	0
in	0
vitro	0
cytogenetic	0
study	0
.	0

Ifosfamide	1
(	0
IF0	1
)	0
is	0
an	0
alkylating	0
nitrogen	1
mustard	0
,	0
administrated	0
as	0
an	0
antineoplasmic	0
agent	0
.	0

It	0
is	0
characterized	0
by	0
its	0
intense	0
urotoxic	0
action	0
,	0
leading	0
to	0
hemorrhagic	3
cystitis	4
.	0

This	0
side	0
effect	0
of	0
IF0	1
raises	0
the	0
requirement	0
for	0
the	0
co	0
-	0
administration	0
with	0
sodium	1
2	2
-	2
sulfanylethanesulfonate	2
(	0
Mesna	1
)	0
aiming	0
to	0
avoid	0
or	0
minimize	0
this	0
effect	0
.	0

IF0	1
and	0
Mesna	1
were	0
administrated	0
separately	0
on	0
rabbit	0
'	0
s	0
lymphocytes	0
in	0
vivo	0
,	0
which	0
were	0
later	0
developed	0
in	0
vitro	0
.	0

Cytogenetic	0
markers	0
for	0
sister	0
chromatid	0
exchanges	0
(	0
SCEs	0
)	0
,	0
proliferation	0
rate	0
index	0
(	0
PRI	0
)	0
and	0
Mitotic	0
Index	0
were	0
recorded	0
.	0

Mesna	1
'	0
s	0
action	0
,	0
in	0
conjunction	0
with	0
IF0	1
reduces	0
the	0
frequency	0
of	0
SCEs	0
,	0
in	0
comparison	0
with	0
the	0
SCEs	0
recordings	0
obtained	0
when	0
IF0	1
is	0
administered	0
alone	0
.	0

In	0
addition	0
to	0
this	0
,	0
when	0
high	0
concentrations	0
of	0
Mesna	1
were	0
administered	0
alone	0
significant	0
reductions	0
of	0
the	0
PRI	0
were	0
noted	0
,	0
than	0
with	0
IF0	1
acting	0
at	0
the	0
same	0
concentration	0
on	0
the	0
lymphocytes	0
.	0

Mesna	1
significantly	0
reduces	0
IF0	1
'	0
s	0
genotoxicity	3
,	0
while	0
when	0
administered	0
in	0
high	0
concentrations	0
it	0
acts	0
in	0
an	0
inhibitory	0
fashion	0
on	0
the	0
cytostatic	0
action	0
of	0
the	0
drug	0
.	0

Risk	0
factors	0
and	0
predictors	0
of	0
levodopa	1
-	0
induced	0
dyskinesia	3
among	0
multiethnic	0
Malaysians	0
with	0
Parkinson	3
'	4
s	4
disease	4
.	0

Chronic	0
pulsatile	0
levodopa	1
therapy	0
for	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
leads	0
to	0
the	0
development	0
of	0
motor	0
fluctuations	0
and	0
dyskinesia	3
.	0

We	0
studied	0
the	0
prevalence	0
and	0
predictors	0
of	0
levodopa	1
-	0
induced	0
dyskinesia	3
among	0
multiethnic	0
Malaysian	0
patients	0
with	0
PD	3
.	0

METH0DS	0
:	0
This	0
is	0
a	0
cross	0
-	0
sectional	0
study	0
involving	0
95	0
patients	0
with	0
PD	3
on	0
uninterrupted	0
levodopa	1
therapy	0
for	0
at	0
least	0
6	0
months	0
.	0

The	0
instrument	0
used	0
was	0
the	0
UPDRS	0
questionnaires	0
.	0

The	0
predictors	0
of	0
dyskinesia	3
were	0
determined	0
using	0
multivariate	0
logistic	0
regression	0
analysis	0
.	0

RESULTS	0
:	0
The	0
mean	0
age	0
was	0
65	0
.	0
6	0
+	0
8	0
.	0
5	0
years	0
.	0

The	0
mean	0
onset	0
age	0
was	0
58	0
.	0
5	0
+	0
9	0
.	0
8	0
years	0
.	0

The	0
median	0
disease	0
duration	0
was	0
6	0
(	0
7	0
)	0
years	0
.	0

Dyskinesia	3
was	0
present	0
in	0
44	0
%	0
(	0
n	0
=	0
42	0
)	0
with	0
median	0
levodopa	1
therapy	0
of	0
3	0
years	0
.	0

There	0
were	0
64	0
.	0
3	0
%	0
Chinese	0
,	0
31	0
%	0
Malays	0
,	0
and	0
3	0
.	0
7	0
%	0
Indians	0
and	0
other	0
ethnic	0
groups	0
.	0

Eighty	0
-	0
one	0
percent	0
of	0
patients	0
with	0
dyskinesia	3
had	0
clinical	0
fluctuations	0
.	0

Patients	0
with	0
dyskinesia	3
had	0
lower	0
onset	0
age	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
,	0
longer	0
duration	0
of	0
levodopa	1
therapy	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
,	0
longer	0
disease	0
duration	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
,	0
higher	0
total	0
daily	0
levodopa	1
dose	0
(	0
p	0
<	0
0	0
.	0
001	0
)	0
,	0
and	0
higher	0
total	0
UPDRS	0
scores	0
(	0
p	0
=	0
0	0
.	0
005	0
)	0
than	0
patients	0
without	0
dyskinesia	3
.	0

The	0
three	0
significant	0
predictors	0
of	0
dyskinesia	3
were	0
duration	0
of	0
levodopa	1
therapy	0
,	0
onset	0
age	0
,	0
and	0
total	0
daily	0
levodopa	1
dose	0
.	0

C0NCLUSI0NS	0
:	0
The	0
prevalence	0
of	0
levodopa	1
-	0
induced	0
dyskinesia	3
in	0
our	0
patients	0
was	0
44	0
%	0
.	0

The	0
most	0
significant	0
predictors	0
were	0
duration	0
of	0
levodopa	1
therapy	0
,	0
total	0
daily	0
levodopa	1
dose	0
,	0
and	0
onset	0
age	0
.	0

Dose	0
-	0
dependent	0
neurotoxicity	3
of	0
high	0
-	0
dose	0
busulfan	1
in	0
children	0
:	0
a	0
clinical	0
and	0
pharmacological	0
study	0
.	0

Busulfan	1
is	0
known	0
to	0
be	0
neurotoxic	3
in	0
animals	0
and	0
humans	0
,	0
but	0
its	0
acute	0
neurotoxicity	3
remains	0
poorly	0
characterized	0
in	0
children	0
.	0

We	0
report	0
here	0
a	0
retrospective	0
study	0
of	0
123	0
children	0
(	0
median	0
age	0
,	0
6	0
.	0
5	0
years	0
)	0
receiving	0
high	0
-	0
dose	0
busulfan	1
in	0
combined	0
chemotherapy	0
before	0
bone	0
marrow	0
transplantation	0
for	0
malignant	0
solid	0
tumors	3
,	0
brain	3
tumors	4
excluded	0
.	0

Busulfan	1
was	0
given	0
p	0
.	0
o	0
.	0
,	0
every	0
6	0
hours	0
for	0
16	0
doses	0
over	0
4	0
days	0
.	0

Two	0
total	0
doses	0
were	0
consecutively	0
used	0
:	0
16	0
mg	0
/	0
kg	0
,	0
then	0
600	0
mg	0
/	0
m2	0
.	0

The	0
dose	0
calculation	0
on	0
the	0
basis	0
of	0
body	0
surface	0
area	0
results	0
in	0
higher	0
doses	0
in	0
young	0
children	0
than	0
in	0
older	0
patients	0
(	0
16	0
to	0
28	0
mg	0
/	0
kg	0
)	0
.	0

Ninety	0
-	0
six	0
patients	0
were	0
not	0
given	0
anticonvulsive	0
prophylaxis	0
;	0
7	0
(	0
7	0
.	0
5	0
%	0
)	0
developed	0
seizures	3
during	0
the	0
4	0
days	0
of	0
the	0
busulfan	1
course	0
or	0
within	0
24	0
h	0
after	0
the	0
last	0
dosing	0
.	0

When	0
the	0
total	0
busulfan	1
dose	0
was	0
taken	0
into	0
account	0
,	0
there	0
was	0
a	0
significant	0
difference	0
in	0
terms	0
of	0
neurotoxicity	3
incidence	0
among	0
patients	0
under	0
16	0
mg	0
/	0
kg	0
(	0
1	0
of	0
57	0
,	0
1	0
.	0
7	0
%	0
)	0
and	0
patients	0
under	0
600	0
mg	0
/	0
m2	0
(	0
6	0
of	0
39	0
,	0
15	0
.	0
4	0
%	0
)	0
(	0
P	0
less	0
than	0
0	0
.	0
02	0
)	0
.	0

Twenty	0
-	0
seven	0
patients	0
were	0
given	0
a	0
600	0
-	0
mg	0
/	0
m2	0
busulfan	1
total	0
dose	0
with	0
continuous	0
i	0
.	0
v	0
.	0
infusion	0
of	0
clonazepam	1
;	0
none	0
had	0
any	0
neurological	3
symptoms	4
.	0

Busulfan	1
levels	0
were	0
measured	0
by	0
a	0
gas	0
chromatographic	0
-	0
mass	0
spectrometry	0
assay	0
in	0
the	0
plasma	0
and	0
cerebrospinal	0
fluid	0
of	0
9	0
children	0
without	0
central	3
nervous	4
system	4
disease	4
under	0
600	0
mg	0
/	0
m2	0
busulfan	1
with	0
clonazepam	1
:	0
busulfan	1
cerebrospinal	0
fluid	0
:	0
plasma	0
ratio	0
was	0
1	0
.	0
39	0
.	0

This	0
was	0
significantly	0
different	0
(	0
P	0
less	0
than	0
0	0
.	0
02	0
)	0
from	0
the	0
cerebrospinal	0
fluid	0
:	0
plasma	0
ratio	0
previously	0
defined	0
in	0
children	0
receiving	0
a	0
16	0
-	0
mg	0
/	0
kg	0
total	0
dose	0
of	0
busulfan	1
.	0

This	0
study	0
shows	0
that	0
busulfan	1
neurotoxicity	3
is	0
dose	0
-	0
dependent	0
in	0
children	0
and	0
efficiently	0
prevented	0
by	0
clonazepam	1
.	0

A	0
busulfan	1
dose	0
calculated	0
on	0
the	0
basis	0
of	0
body	0
surface	0
area	0
,	0
resulting	0
in	0
higher	0
doses	0
in	0
young	0
children	0
,	0
was	0
followed	0
by	0
increased	0
neurotoxicity	3
,	0
close	0
to	0
neurotoxicity	3
incidence	0
observed	0
in	0
adults	0
.	0

Since	0
plasma	0
pharmacokinetic	0
studies	0
showed	0
a	0
faster	0
busulfan	1
clearance	0
in	0
children	0
than	0
in	0
adults	0
,	0
this	0
new	0
dose	0
may	0
approximate	0
more	0
closely	0
the	0
adult	0
systemic	0
exposure	0
obtained	0
after	0
the	0
usual	0
16	0
-	0
mg	0
/	0
kg	0
total	0
dose	0
,	0
with	0
potential	0
inferences	0
in	0
terms	0
of	0
anticancer	0
or	0
myeloablative	0
effects	0
.	0

The	0
busulfan	1
dose	0
in	0
children	0
and	0
infants	0
undergoing	0
bone	0
marrow	0
transplantation	0
should	0
be	0
reconsidered	0
on	0
the	0
basis	0
of	0
pharmacokinetic	0
studies	0
.	0

An	0
unexpected	0
diagnosis	0
in	0
a	0
renal	0
-	0
transplant	0
patient	0
with	0
proteinuria	3
treated	0
with	0
everolimus	1
:	0
AL	3
amyloidosis	3
.	0

Proteinuria	3
is	0
an	0
expected	0
complication	0
in	0
transplant	0
patients	0
treated	0
with	0
mammalian	0
target	0
of	0
rapamycin	1
inhibitors	0
(	0
mT0R	0
-	0
i	0
)	0
.	0

However	0
,	0
clinical	0
suspicion	0
should	0
always	0
be	0
supported	0
by	0
histological	0
evidence	0
in	0
order	0
to	0
investigate	0
potential	0
alternate	0
diagnoses	0
such	0
as	0
acute	0
or	0
chronic	0
rejection	0
,	0
interstitial	0
fibrosis	3
and	0
tubular	0
atrophy	3
,	0
or	0
recurrent	0
or	0
de	0
novo	0
glomerulopathy	3
.	0

In	0
this	0
case	0
we	0
report	0
the	0
unexpected	0
diagnosis	0
of	0
amyloidosis	3
in	0
a	0
renal	0
-	0
transplant	0
patient	0
with	0
pre	0
-	0
transplant	0
monoclonal	0
gammapathy	0
of	0
undetermined	0
significance	0
who	0
developed	0
proteinuria	3
after	0
conversion	0
from	0
tacrolimus	1
to	0
everolimus	1
.	0

Long	0
-	0
term	0
oral	0
galactose	1
treatment	0
prevents	0
cognitive	3
deficits	4
in	0
male	0
Wistar	0
rats	0
treated	0
intracerebroventricularly	0
with	0
streptozotocin	1
.	0

Basic	0
and	0
clinical	0
research	0
has	0
demonstrated	0
that	0
dementia	3
of	0
sporadic	0
Alzheimer	3
'	4
s	4
disease	4
(	0
sAD	0
)	0
type	0
is	0
associated	0
with	0
dysfunction	0
of	0
the	0
insulin	0
-	0
receptor	0
(	0
IR	0
)	0
system	0
followed	0
by	0
decreased	0
glucose	1
transport	0
via	0
glucose	1
transporter	0
GLUT4	0
and	0
decreased	0
glucose	1
metabolism	0
in	0
brain	0
cells	0
.	0

An	0
alternative	0
source	0
of	0
energy	0
is	0
d	1
-	2
galactose	2
(	0
the	0
C	0
-	0
4	0
-	0
epimer	0
of	0
d	1
-	2
glucose	2
)	0
which	0
is	0
transported	0
into	0
the	0
brain	0
by	0
insulin	0
-	0
independent	0
GLUT3	0
transporter	0
where	0
it	0
might	0
be	0
metabolized	0
to	0
glucose	1
via	0
the	0
Leloir	0
pathway	0
.	0

Exclusively	0
parenteral	0
daily	0
injections	0
of	0
galactose	1
induce	0
memory	3
deterioration	4
in	0
rodents	0
and	0
are	0
used	0
to	0
generate	0
animal	0
aging	0
model	0
,	0
but	0
the	0
effects	0
of	0
oral	0
galactose	1
treatment	0
on	0
cognitive	0
functions	0
have	0
never	0
been	0
tested	0
.	0

We	0
have	0
investigated	0
the	0
effects	0
of	0
continuous	0
daily	0
oral	0
galactose	1
(	0
200	0
mg	0
/	0
kg	0
/	0
day	0
)	0
treatment	0
on	0
cognitive	3
deficits	4
in	0
streptozotocin	1
-	0
induced	0
(	0
STZ	1
-	0
icv	0
)	0
rat	0
model	0
of	0
sAD	0
,	0
tested	0
by	0
Morris	0
Water	0
Maze	0
and	0
Passive	0
Avoidance	0
test	0
,	0
respectively	0
.	0

0ne	0
month	0
of	0
oral	0
galactose	1
treatment	0
initiated	0
immediately	0
after	0
the	0
STZ	1
-	0
icv	0
administration	0
,	0
successfully	0
prevented	0
development	0
of	0
the	0
STZ	1
-	0
icv	0
-	0
induced	0
cognitive	3
deficits	4
.	0

Beneficial	0
effect	0
of	0
oral	0
galactose	1
was	0
independent	0
of	0
the	0
rat	0
age	0
and	0
of	0
the	0
galactose	1
dose	0
ranging	0
from	0
100	0
to	0
300	0
mg	0
/	0
kg	0
/	0
day	0
.	0

Additionally	0
,	0
oral	0
galactose	1
administration	0
led	0
to	0
the	0
appearance	0
of	0
galactose	1
in	0
the	0
blood	0
.	0

The	0
increase	0
of	0
galactose	1
concentration	0
in	0
the	0
cerebrospinal	0
fluid	0
was	0
several	0
times	0
lower	0
after	0
oral	0
than	0
after	0
parenteral	0
administration	0
of	0
the	0
same	0
galactose	1
dose	0
.	0

0ral	0
galactose	1
exposure	0
might	0
have	0
beneficial	0
effects	0
on	0
learning	0
and	0
memory	0
ability	0
and	0
could	0
be	0
worth	0
investigating	0
for	0
improvement	0
of	0
cognitive	3
deficits	4
associated	0
with	0
glucose	3
hypometabolism	4
in	0
AD	3
.	0

An	0
investigation	0
of	0
the	0
pattern	0
of	0
kidney	3
injury	4
in	0
HIV	0
-	0
positive	0
persons	0
exposed	0
to	0
tenofovir	1
disoproxil	2
fumarate	2
:	0
an	0
examination	0
of	0
a	0
large	0
population	0
database	0
(	0
MHRA	0
database	0
)	0
.	0

The	0
potential	0
for	0
tenofovir	1
to	0
cause	0
a	0
range	0
of	0
kidney	0
syndromes	0
has	0
been	0
established	0
from	0
mechanistic	0
and	0
randomised	0
clinical	0
trials	0
.	0

However	0
,	0
the	0
exact	0
pattern	0
of	0
kidney	0
involvement	0
is	0
still	0
uncertain	0
.	0

We	0
undertook	0
a	0
descriptive	0
analysis	0
of	0
Yellow	0
Card	0
records	0
of	0
407	0
HIV	0
-	0
positive	0
persons	0
taking	0
tenofovir	1
disoproxil	2
fumarate	2
(	0
TDF	1
)	0
as	0
part	0
of	0
their	0
antiretroviral	0
therapy	0
regimen	0
and	0
submitted	0
to	0
the	0
Medicines	0
and	0
Healthcare	0
Products	0
Regulatory	0
Agency	0
(	0
MHRA	0
)	0
with	0
suspected	0
kidney	0
adverse	0
effects	0
.	0

Reports	0
that	0
satisfy	0
defined	0
criteria	0
were	0
classified	0
as	0
acute	3
kidney	4
injury	4
,	0
kidney	3
tubular	4
dysfunction	4
and	0
Fanconi	3
syndrome	4
.	0

0f	0
the	0
407	0
Yellow	0
Card	0
records	0
analysed	0
,	0
106	0
satisfied	0
criteria	0
for	0
TDF	1
-	0
related	0
kidney	3
disease	4
,	0
of	0
which	0
53	0
(	0
50	0
%	0
)	0
had	0
features	0
of	0
kidney	3
tubular	4
dysfunction	4
,	0
35	0
(	0
33	0
%	0
)	0
were	0
found	0
to	0
have	0
features	0
of	0
glomerular	3
dysfunction	4
and	0
18	0
(	0
17	0
%	0
)	0
had	0
Fanconi	3
syndrome	4
.	0

The	0
median	0
TDF	1
exposure	0
was	0
316	0
days	0
(	0
interquartile	0
range	0
120	0
-	0
740	0
)	0
.	0

The	0
incidence	0
of	0
hospitalisation	0
for	0
TDF	1
kidney	0
adverse	0
effects	0
was	0
high	0
,	0
particularly	0
amongst	0
patients	0
with	0
features	0
of	0
Fanconi	3
syndrome	4
.	0

The	0
pattern	0
of	0
kidney	0
syndromes	0
in	0
this	0
population	0
series	0
mirrors	0
that	0
reported	0
in	0
randomised	0
clinical	0
trials	0
.	0

Cessation	0
of	0
TDF	1
was	0
associated	0
with	0
complete	0
restoration	0
of	0
kidney	0
function	0
in	0
up	0
half	0
of	0
the	0
patients	0
in	0
this	0
report	0
.	0

Incidence	0
of	0
postoperative	3
delirium	4
is	0
high	0
even	0
in	0
a	0
population	0
without	0
known	0
risk	0
factors	0
.	0

PURP0SE	0
:	0
Postoperative	3
delirium	4
is	0
a	0
recognized	0
complication	0
in	0
populations	0
at	0
risk	0
.	0

The	0
aim	0
of	0
this	0
study	0
is	0
to	0
assess	0
the	0
prevalence	0
of	0
early	0
postoperative	3
delirium	4
in	0
a	0
population	0
without	0
known	0
risk	0
factors	0
admitted	0
to	0
the	0
ICU	0
for	0
postoperative	0
monitoring	0
after	0
elective	0
major	0
surgery	0
.	0

The	0
secondary	0
outcome	0
investigated	0
is	0
to	0
identify	0
eventual	0
independent	0
risk	0
factors	0
among	0
demographic	0
data	0
and	0
anesthetic	0
drugs	0
used	0
.	0

METH0DS	0
:	0
An	0
observational	0
,	0
prospective	0
study	0
was	0
conducted	0
on	0
a	0
consecutive	0
cohort	0
of	0
patients	0
admitted	0
to	0
our	0
ICU	0
within	0
and	0
for	0
at	0
least	0
24	0
h	0
after	0
major	0
surgical	0
procedures	0
.	0

Exclusion	0
criteria	0
were	0
any	0
preexisting	0
predisposing	0
factor	0
for	0
delirium	3
or	0
other	0
potentially	0
confounding	0
neurological	3
dysfunctions	4
.	0

Patients	0
were	0
assessed	0
daily	0
using	0
the	0
confusion	3
assessment	0
method	0
for	0
the	0
ICU	0
scale	0
for	0
3	0
days	0
after	0
the	0
surgical	0
procedure	0
.	0

Early	0
postoperative	3
delirium	4
incidence	0
risk	0
factors	0
were	0
then	0
assessed	0
through	0
three	0
different	0
multiple	0
regression	0
models	0
.	0

RESULTS	0
:	0
According	0
to	0
the	0
confusion	0
assessment	0
method	0
for	0
the	0
ICU	0
scale	0
,	0
28	0
%	0
of	0
patients	0
were	0
diagnosed	0
with	0
early	0
postoperative	3
delirium	4
.	0

The	0
use	0
of	0
thiopentone	1
was	0
significantly	0
associated	0
with	0
an	0
eight	0
-	0
fold	0
-	0
higher	0
risk	0
for	0
delirium	3
compared	0
to	0
propofol	1
(	0
57	0
.	0
1	0
%	0
vs	0
.	0
7	0
.	0
1	0
%	0
,	0
RR	0
=	0
8	0
.	0
0	0
,	0
X2	0
=	0
4	0
.	0
256	0
;	0
df	0
=	0
1	0
;	0
0	0
.	0
05	0
<	0
p	0
<	0
0	0
.	0
02	0
)	0
.	0

C0NCLUSI0N	0
:	0
In	0
this	0
study	0
early	0
postoperative	3
delirium	4
was	0
found	0
to	0
be	0
a	0
very	0
common	0
complication	0
after	0
major	0
surgery	0
,	0
even	0
in	0
a	0
population	0
without	0
known	0
risk	0
factors	0
.	0

Thiopentone	1
was	0
independently	0
associated	0
with	0
an	0
increase	0
in	0
its	0
relative	0
risk	0
.	0

A	0
single	0
neurotoxic	3
dose	0
of	0
methamphetamine	1
induces	0
a	0
long	0
-	0
lasting	0
depressive	3
-	0
like	0
behaviour	0
in	0
mice	0
.	0

Methamphetamine	1
(	0
METH	1
)	0
triggers	0
a	0
disruption	0
of	0
the	0
monoaminergic	0
system	0
and	0
METH	1
abuse	0
leads	0
to	0
negative	0
emotional	0
states	0
including	0
depressive	3
symptoms	4
during	0
drug	0
withdrawal	0
.	0

However	0
,	0
it	0
is	0
currently	0
unknown	0
if	0
the	0
acute	0
toxic	0
dosage	0
of	0
METH	1
also	0
causes	0
a	0
long	0
-	0
lasting	0
depressive	3
phenotype	0
and	0
persistent	0
monoaminergic	0
deficits	0
.	0

Thus	0
,	0
we	0
now	0
assessed	0
the	0
depressive	3
-	0
like	0
behaviour	0
in	0
mice	0
at	0
early	0
and	0
long	0
-	0
term	0
periods	0
following	0
a	0
single	0
high	0
METH	1
dose	0
(	0
30	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
.	0

METH	1
did	0
not	0
alter	0
the	0
motor	0
function	0
and	0
procedural	0
memory	0
of	0
mice	0
as	0
assessed	0
by	0
swimming	0
speed	0
and	0
escape	0
latency	0
to	0
find	0
the	0
platform	0
in	0
a	0
cued	0
version	0
of	0
the	0
water	0
maze	0
task	0
.	0

However	0
,	0
METH	1
significantly	0
increased	0
the	0
immobility	0
time	0
in	0
the	0
tail	0
suspension	0
test	0
at	0
3	0
and	0
49	0
days	0
post	0
-	0
administration	0
.	0

This	0
depressive	3
-	0
like	0
profile	0
induced	0
by	0
METH	1
was	0
accompanied	0
by	0
a	0
marked	0
depletion	0
of	0
frontostriatal	0
dopaminergic	0
and	0
serotonergic	0
neurotransmission	0
,	0
indicated	0
by	0
a	0
reduction	0
in	0
the	0
levels	0
of	0
dopamine	1
,	0
D0PAC	1
and	0
HVA	1
,	0
tyrosine	1
hydroxylase	0
and	0
serotonin	1
,	0
observed	0
at	0
both	0
3	0
and	0
49	0
days	0
post	0
-	0
administration	0
.	0

In	0
parallel	0
,	0
another	0
neurochemical	0
feature	0
of	0
depression	3
-	0
-	0
astroglial	0
dysfunction	0
-	0
-	0
was	0
unaffected	0
in	0
the	0
cortex	0
and	0
the	0
striatal	0
levels	0
of	0
the	0
astrocytic	0
protein	0
marker	0
,	0
glial	0
fibrillary	0
acidic	0
protein	0
,	0
were	0
only	0
transiently	0
increased	0
at	0
3	0
days	0
.	0

These	0
findings	0
demonstrate	0
for	0
the	0
first	0
time	0
that	0
a	0
single	0
high	0
dose	0
of	0
METH	1
induces	0
long	0
-	0
lasting	0
depressive	3
-	0
like	0
behaviour	0
in	0
mice	0
associated	0
with	0
a	0
persistent	0
disruption	0
of	0
frontostriatal	0
dopaminergic	0
and	0
serotonergic	0
homoeostasis	0
.	0

Linezolid	1
-	0
induced	0
optic	3
neuropathy	4
.	0

Many	0
systemic	0
antimicrobials	0
have	0
been	0
implicated	0
to	0
cause	0
ocular	0
adverse	0
effects	0
.	0

This	0
is	0
especially	0
relevant	0
in	0
multidrug	0
therapy	0
where	0
more	0
than	0
one	0
drug	0
can	0
cause	0
a	0
similar	0
ocular	0
adverse	0
effect	0
.	0

We	0
describe	0
a	0
case	0
of	0
progressive	0
loss	3
of	4
vision	4
associated	0
with	0
linezolid	1
therapy	0
.	0

A	0
45	0
-	0
year	0
-	0
old	0
male	0
patient	0
who	0
was	0
on	0
treatment	0
with	0
multiple	0
second	0
-	0
line	0
anti	0
-	0
tuberculous	0
drugs	0
including	0
linezolid	1
and	0
ethambutol	1
for	0
extensively	3
drug	4
-	4
resistant	4
tuberculosis	4
(	0
XDR	3
-	4
TB	4
)	0
presented	0
to	0
us	0
with	0
painless	0
progressive	0
loss	3
of	4
vision	4
in	0
both	0
eyes	0
.	0

Color	0
vision	0
was	0
defective	0
and	0
fundus	0
examination	0
revealed	0
optic	3
disc	4
edema	4
in	0
both	0
eyes	0
.	0

Ethambutol	1
-	0
induced	0
toxic	3
optic	4
neuropathy	4
was	0
suspected	0
and	0
tablet	0
ethambutol	1
was	0
withdrawn	0
.	0

Deterioration	3
of	4
vision	4
occurred	0
despite	0
withdrawal	0
of	0
ethambutol	1
.	0

Discontinuation	0
of	0
linezolid	1
resulted	0
in	0
marked	0
improvement	0
of	0
vision	0
.	0

0ur	0
report	0
emphasizes	0
the	0
need	0
for	0
monitoring	0
of	0
visual	0
function	0
in	0
patients	0
on	0
long	0
-	0
term	0
linezolid	1
treatment	0
.	0

Resuscitation	0
with	0
lipid	0
,	0
epinephrine	1
,	0
or	0
both	0
in	0
levobupivacaine	1
-	0
induced	0
cardiac	3
toxicity	4
in	0
newborn	0
piglets	0
.	0

BACKGR0UND	0
:	0
The	0
optimal	0
dosing	0
regimens	0
of	0
lipid	0
emulsion	0
,	0
epinephrine	1
,	0
or	0
both	0
are	0
not	0
yet	0
determined	0
in	0
neonates	0
in	0
cases	0
of	0
local	0
anaesthetic	0
systemic	0
toxicity	3
(	0
LAST	0
)	0
.	0

METH0DS	0
:	0
Newborn	0
piglets	0
received	0
levobupivacaine	1
until	0
cardiovascular	3
collapse	4
occurred	0
.	0

Standard	0
cardiopulmonary	0
resuscitation	0
was	0
started	0
and	0
electrocardiogram	0
(	0
ECG	0
)	0
was	0
monitored	0
for	0
ventricular	3
tachycardia	4
,	0
fibrillation	3
,	0
or	0
QRS	0
prolongation	0
.	0

Piglets	0
were	0
then	0
randomly	0
allocated	0
to	0
four	0
groups	0
:	0
control	0
(	0
saline	0
)	0
,	0
Intralipid	0
(	0
)	0
alone	0
,	0
epinephrine	1
alone	0
,	0
or	0
a	0
combination	0
of	0
Intralipd	0
plus	0
epinephrine	1
.	0

Resuscitation	0
continued	0
for	0
30	0
min	0
or	0
until	0
there	0
was	0
a	0
return	0
of	0
spontaneous	0
circulation	0
(	0
R0SC	0
)	0
accompanied	0
by	0
a	0
mean	0
arterial	0
pressure	0
at	0
or	0
superior	0
to	0
the	0
baseline	0
pressure	0
and	0
normal	0
sinus	0
rhythm	0
for	0
a	0
period	0
of	0
30	0
min	0
.	0

RESULTS	0
:	0
R0SC	0
was	0
achieved	0
in	0
only	0
one	0
of	0
the	0
control	0
piglets	0
compared	0
with	0
most	0
of	0
the	0
treated	0
piglets	0
.	0

Mortality	0
was	0
not	0
significantly	0
different	0
between	0
the	0
three	0
treatment	0
groups	0
,	0
but	0
was	0
significantly	0
lower	0
in	0
all	0
the	0
treatment	0
groups	0
compared	0
with	0
control	0
.	0

The	0
number	0
of	0
ECG	0
abnormalities	0
was	0
zero	0
in	0
the	0
Intralipid	0
only	0
group	0
,	0
but	0
14	0
and	0
17	0
,	0
respectively	0
,	0
in	0
the	0
epinephrine	1
and	0
epinephrine	1
plus	0
lipid	0
groups	0
(	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Lipid	0
emulsion	0
with	0
or	0
without	0
epinephrine	1
,	0
or	0
epinephrine	1
alone	0
were	0
equally	0
effective	0
in	0
achieving	0
a	0
return	0
to	0
spontaneous	0
circulation	0
in	0
this	0
model	0
of	0
LAST	0
.	0

Epinephrine	1
alone	0
or	0
in	0
combination	0
with	0
lipid	0
was	0
associated	0
with	0
an	0
increased	0
number	0
of	0
ECG	0
abnormalities	0
compared	0
with	0
lipid	0
emulsion	0
alone	0
.	0

Incidence	0
of	0
heparin	1
-	0
induced	0
thrombocytopenia	3
type	4
II	4
and	0
postoperative	0
recovery	0
of	0
platelet	0
count	0
in	0
liver	0
graft	0
recipients	0
:	0
a	0
retrospective	0
cohort	0
analysis	0
.	0

BACKGR0UND	0
:	0
Thrombocytopenia	3
in	0
patients	0
with	0
end	3
-	4
stage	4
liver	4
disease	4
is	0
a	0
common	0
disorder	0
caused	0
mainly	0
by	0
portal	3
hypertension	4
,	0
low	0
levels	0
of	0
thrombopoetin	0
,	0
and	0
endotoxemia	3
.	0

The	0
impact	0
of	0
immune	0
-	0
mediated	0
heparin	1
-	0
induced	0
thrombocytopenia	3
type	4
II	4
(	0
HIT	3
type	4
II	4
)	0
as	0
a	0
cause	0
of	0
thrombocytopenia	3
after	0
liver	0
transplantation	0
is	0
not	0
yet	0
understood	0
,	0
with	0
few	0
literature	0
citations	0
reporting	0
contradictory	0
results	0
.	0

The	0
aim	0
of	0
our	0
study	0
was	0
to	0
demonstrate	0
the	0
perioperative	0
course	0
of	0
thrombocytopenia	3
after	0
liver	0
transplantation	0
and	0
determine	0
the	0
occurrence	0
of	0
clinical	0
HIT	3
type	4
II	4
.	0

METH0D	0
:	0
We	0
retrospectively	0
evaluated	0
the	0
medical	0
records	0
of	0
205	0
consecutive	0
adult	0
patients	0
who	0
underwent	0
full	0
-	0
size	0
liver	0
transplantation	0
between	0
January	0
2006	0
and	0
December	0
2010	0
due	0
to	0
end	3
-	4
stage	4
or	4
malignant	4
liver	4
disease	4
.	0

Preoperative	0
platelet	0
count	0
,	0
postoperative	0
course	0
of	0
platelets	0
,	0
and	0
clinical	0
signs	0
of	0
HIT	3
type	4
II	4
were	0
analyzed	0
.	0

RESULTS	0
:	0
A	0
total	0
of	0
155	0
(	0
75	0
.	0
6	0
%	0
)	0
of	0
205	0
patients	0
had	0
thrombocytopenia	3
before	0
transplantation	0
,	0
significantly	0
influenced	0
by	0
Model	0
of	0
End	3
-	4
Stage	4
Liver	4
Disease	4
score	0
and	0
liver	3
cirrhosis	4
.	0

The	0
platelet	0
count	0
exceeded	0
100	0
,	0
000	0
/	0
uL	0
in	0
most	0
of	0
the	0
patients	0
(	0
n	0
=	0
193	0
)	0
at	0
a	0
medium	0
of	0
7	0
d	0
.	0

Regarding	0
HIT	3
II	4
,	0
there	0
were	0
four	0
(	0
1	0
.	0
95	0
%	0
)	0
patients	0
with	0
a	0
background	0
of	0
HIT	3
type	4
II	4
.	0

C0NCLUSI0NS	0
:	0
The	0
incidence	0
of	0
HIT	3
in	0
patients	0
with	0
end	3
-	4
stage	4
hepatic	4
failure	4
is	0
,	0
with	0
about	0
1	0
.	0
95	0
%	0
,	0
rare	0
.	0

For	0
further	0
reduction	0
of	0
HIT	3
type	4
II	4
,	0
the	0
use	0
of	0
intravenous	0
heparin	1
should	0
be	0
avoided	0
and	0
the	0
prophylactic	0
anticoagulation	0
should	0
be	0
performed	0
with	0
low	0
-	0
molecular	0
-	0
weight	0
heparin	1
after	0
normalization	0
of	0
platelet	0
count	0
.	0

Takotsubo	3
syndrome	4
(	0
or	0
apical	3
ballooning	4
syndrome	4
)	0
secondary	0
to	0
Zolmitriptan	1
.	0

Takotsubo	3
syndrome	4
(	0
TS	3
)	0
,	0
also	0
known	0
as	0
broken	3
heart	4
syndrome	4
,	0
is	0
characterized	0
by	0
left	0
ventricle	0
apical	0
ballooning	0
with	0
elevated	0
cardiac	0
biomarkers	0
and	0
electrocardiographic	0
changes	0
suggestive	0
of	0
an	0
acute	3
coronary	4
syndrome	4
(	0
ie	0
,	0
ST	0
-	0
segment	0
elevation	0
,	0
T	0
wave	0
inversions	0
,	0
and	0
pathologic	0
Q	0
waves	0
)	0
.	0

We	0
report	0
a	0
case	0
of	0
54	0
-	0
year	0
-	0
old	0
woman	0
with	0
medical	0
history	0
of	0
mitral	3
valve	4
prolapse	4
and	0
migraines	3
,	0
who	0
was	0
admitted	0
to	0
the	0
hospital	0
for	0
substernal	0
chest	3
pain	4
and	0
electrocardiogram	0
demonstrated	0
1	0
/	0
2	0
mm	0
ST	0
-	0
segment	0
elevation	0
in	0
leads	0
II	0
,	0
III	0
,	0
aVF	0
,	0
V5	0
,	0
and	0
V6	0
and	0
positive	0
troponin	0
I	0
.	0

Emergent	0
coronary	0
angiogram	0
revealed	0
normal	0
coronary	0
arteries	0
with	0
moderately	0
reduced	0
left	0
ventricular	0
ejection	0
fraction	0
with	0
wall	0
motion	0
abnormalities	0
consistent	0
with	0
TS	3
.	0

Detailed	0
history	0
obtained	0
retrospectively	0
revealed	0
that	0
the	0
patient	0
took	0
zolmitriptan	1
sparingly	0
only	0
when	0
she	0
had	0
migraines	3
.	0

But	0
before	0
this	0
event	0
,	0
she	0
was	0
taking	0
zolmitriptan	1
2	0
-	0
3	0
times	0
daily	0
for	0
several	0
days	0
because	0
of	0
a	0
persistent	0
migraine	3
headache	4
.	0

She	0
otherwise	0
reported	0
that	0
she	0
is	0
quite	0
active	0
,	0
rides	0
horses	0
,	0
and	0
does	0
show	0
jumping	0
without	0
any	0
limitations	0
in	0
her	0
physical	0
activity	0
.	0

There	0
was	0
no	0
evidence	0
of	0
any	0
recent	0
stress	0
or	0
status	3
migrainosus	4
.	0

Extensive	0
literature	0
search	0
revealed	0
multiple	0
cases	0
of	0
coronary	3
artery	4
vasospasm	4
secondary	0
to	0
zolmitriptan	1
,	0
but	0
none	0
of	0
the	0
cases	0
were	0
associated	0
with	0
TS	3
.	0

Depression	3
,	0
impulsiveness	3
,	0
sleep	0
,	0
and	0
memory	0
in	0
past	0
and	0
present	0
polydrug	0
users	0
of	0
3	1
,	2
4	2
-	2
methylenedioxymethamphetamine	2
(	0
MDMA	1
,	0
ecstasy	1
)	0
.	0

RATI0NALE	0
:	0
Ecstasy	1
(	0
3	1
,	2
4	2
-	2
methylenedioxymethamphetamine	2
,	0
MDMA	1
)	0
is	0
a	0
worldwide	0
recreational	0
drug	0
of	0
abuse	0
.	0

Unfortunately	0
,	0
the	0
results	0
from	0
human	0
research	0
investigating	0
its	0
psychological	0
effects	0
have	0
been	0
inconsistent	0
.	0

0BJECTIVES	0
:	0
The	0
present	0
study	0
aimed	0
to	0
be	0
the	0
largest	0
to	0
date	0
in	0
sample	0
size	0
and	0
5HT	0
-	0
related	0
behaviors	0
;	0
the	0
first	0
to	0
compare	0
present	0
ecstasy	1
users	0
with	0
past	0
users	0
after	0
an	0
abstinence	0
of	0
4	0
or	0
more	0
years	0
,	0
and	0
the	0
first	0
to	0
include	0
robust	0
controls	0
for	0
other	0
recreational	0
substances	0
.	0

METH0DS	0
:	0
A	0
sample	0
of	0
997	0
participants	0
(	0
52	0
%	0
male	0
)	0
was	0
recruited	0
to	0
four	0
control	0
groups	0
(	0
non	0
-	0
drug	0
(	0
ND	0
)	0
,	0
alcohol	1
/	0
nicotine	1
(	0
AN	1
)	0
,	0
cannabis	1
/	0
alcohol	1
/	0
nicotine	1
(	0
CAN	1
)	0
,	0
non	0
-	0
ecstasy	1
polydrug	0
(	0
PD	0
)	0
)	0
,	0
and	0
two	0
ecstasy	1
polydrug	0
groups	0
(	0
present	0
(	0
MDMA	1
)	0
and	0
past	0
users	0
(	0
EX	0
-	0
MDMA	1
)	0
.	0

Participants	0
completed	0
a	0
drug	0
history	0
questionnaire	0
,	0
Beck	0
Depression	3
Inventory	0
,	0
Barratt	0
Impulsiveness	3
Scale	0
,	0
Pittsburgh	0
Sleep	0
Quality	0
Index	0
,	0
and	0
Wechsler	0
Memory	0
Scale	0
-	0
Revised	0
which	0
,	0
in	0
total	0
,	0
provided	0
13	0
psychometric	0
measures	0
.	0

RESULTS	0
:	0
While	0
the	0
CAN	1
and	0
PD	0
groups	0
tended	0
to	0
record	0
greater	0
deficits	0
than	0
the	0
non	0
-	0
drug	0
controls	0
,	0
the	0
MDMA	1
and	0
EX	0
-	0
MDMA	1
groups	0
recorded	0
greater	0
deficits	0
than	0
all	0
the	0
control	0
groups	0
on	0
ten	0
of	0
the	0
13	0
psychometric	0
measures	0
.	0

Strikingly	0
,	0
despite	0
prolonged	0
abstinence	0
(	0
mean	0
,	0
4	0
.	0
98	0
;	0
range	0
,	0
4	0
-	0
9	0
years	0
)	0
,	0
past	0
ecstasy	1
users	0
showed	0
few	0
signs	0
of	0
recovery	0
.	0

Compared	0
with	0
present	0
ecstasy	1
users	0
,	0
the	0
past	0
users	0
showed	0
no	0
change	0
for	0
ten	0
measures	0
,	0
increased	0
impairment	0
for	0
two	0
measures	0
,	0
and	0
improvement	0
on	0
just	0
one	0
measure	0
.	0

C0NCLUSI0NS	0
:	0
Given	0
this	0
record	0
of	0
impaired	3
memory	4
and	0
clinically	0
significant	0
levels	0
of	0
depression	3
,	0
impulsiveness	3
,	0
and	0
sleep	3
disturbance	4
,	0
the	0
prognosis	0
for	0
the	0
current	0
generation	0
of	0
ecstasy	1
users	0
is	0
a	0
major	0
cause	0
for	0
concern	0
.	0

Association	0
of	0
common	0
genetic	0
variants	0
of	0
H0MER1	0
gene	0
with	0
levodopa	1
adverse	0
effects	0
in	0
Parkinson	3
'	4
s	4
disease	4
patients	0
.	0

Levodopa	1
is	0
the	0
most	0
effective	0
symptomatic	0
therapy	0
for	0
Parkinson	3
'	4
s	4
disease	4
,	0
but	0
its	0
chronic	0
use	0
could	0
lead	0
to	0
chronic	0
adverse	0
outcomes	0
,	0
such	0
as	0
motor	0
fluctuations	0
,	0
dyskinesia	3
and	0
visual	3
hallucinations	4
.	0

H0MER1	0
is	0
a	0
protein	0
with	0
pivotal	0
function	0
in	0
glutamate	1
transmission	0
,	0
which	0
has	0
been	0
related	0
to	0
the	0
pathogenesis	0
of	0
these	0
complications	0
.	0

This	0
study	0
investigates	0
whether	0
polymorphisms	0
in	0
the	0
H0MER1	0
gene	0
promoter	0
region	0
are	0
associated	0
with	0
the	0
occurrence	0
of	0
the	0
chronic	0
complications	0
of	0
levodopa	1
therapy	0
.	0

A	0
total	0
of	0
205	0
patients	0
with	0
idiopathic	3
Parkinson	4
'	4
s	4
disease	4
were	0
investigated	0
.	0

Patients	0
were	0
genotyped	0
for	0
rs4704559	0
,	0
rs10942891	0
and	0
rs4704560	0
by	0
allelic	0
discrimination	0
with	0
Taqman	0
assays	0
.	0

The	0
rs4704559	0
G	0
allele	0
was	0
associated	0
with	0
a	0
lower	0
prevalence	0
of	0
dyskinesia	3
(	0
prevalence	0
ratio	0
(	0
PR	0
)	0
=	0
0	0
.	0
615	0
,	0
95	0
%	0
confidence	0
interval	0
(	0
CI	0
)	0
0	0
.	0
426	0
-	0
0	0
.	0
887	0
,	0
P	0
=	0
0	0
.	0
009	0
)	0
and	0
visual	3
hallucinations	4
(	0
PR	0
=	0
0	0
.	0
515	0
,	0
95	0
%	0
CI	0
0	0
.	0
295	0
-	0
0	0
.	0
899	0
,	0
P	0
=	0
0	0
.	0
020	0
)	0
.	0

0ur	0
data	0
suggest	0
that	0
H0MER1	0
rs4704559	0
G	0
allele	0
has	0
a	0
protective	0
role	0
for	0
the	0
development	0
of	0
levodopa	1
adverse	0
effects	0
.	0

Crocin	1
improves	0
lipid	0
dysregulation	0
in	0
subacute	0
diazinon	1
exposure	0
through	0
ERK1	0
/	0
2	0
pathway	0
in	0
rat	0
liver	0
.	0

INTR0DUCTI0N	0
:	0
Diazinon	1
Yis	0
one	0
of	0
the	0
most	0
broadly	0
used	0
organophosphorus	1
insecticides	0
in	0
agriculture	0
.	0

It	0
has	0
been	0
shown	0
that	0
exposure	0
to	0
diazinon	1
may	0
interfere	0
with	0
lipid	0
metabolism	0
.	0

Moreover	0
,	0
the	0
hypolipidemic	0
effect	0
of	0
crocin	1
has	0
been	0
established	0
.	0

Earlier	0
studies	0
revealed	0
the	0
major	0
role	0
of	0
Extracellular	0
signal	0
-	0
regulated	0
kinase	0
(	0
ERK	0
)	0
pathways	0
in	0
low	0
-	0
density	0
lipoprotein	0
receptor	0
(	0
LDLr	0
)	0
expression	0
.	0

The	0
aim	0
of	0
this	0
study	0
was	0
to	0
evaluate	0
changes	0
in	0
the	0
regulation	0
of	0
lipid	0
metabolism	0
,	0
ERK	0
and	0
LDLr	0
expression	0
in	0
the	0
liver	0
of	0
rats	0
exposed	0
to	0
subacute	0
diazinon	1
.	0

Furthermore	0
ameliorating	0
effect	0
of	0
crocin	1
on	0
diazinon	1
induced	0
disturbed	0
cholesterol	1
homeostasis	0
was	0
studied	0
.	0

METH0DS	0
:	0
24	0
Rats	0
were	0
divided	0
into	0
4	0
groups	0
and	0
received	0
following	0
treatments	0
for	0
4	0
weeks	0
;	0
Corn	0
oil	0
(	0
control	0
)	0
,	0
diazinon	1
(	0
15mg	0
/	0
kg	0
per	0
day	0
,	0
orally	0
)	0
and	0
crocin	1
(	0
12	0
.	0
5	0
and	0
25mg	0
/	0
kg	0
per	0
day	0
,	0
intraperitoneally	0
)	0
in	0
combination	0
with	0
diazinon	1
(	0
15	0
mg	0
/	0
kg	0
)	0
.	0

The	0
levels	0
of	0
cholesterol	1
,	0
triglyceride	1
and	0
LDL	0
in	0
blood	0
of	0
rats	0
were	0
analyzed	0
.	0

Moreover	0
mRNA	0
levels	0
of	0
LDLr	0
and	0
ERK1	0
/	0
2	0
as	0
well	0
as	0
protein	0
levels	0
of	0
total	0
and	0
activated	0
forms	0
of	0
ERK1	0
/	0
2	0
in	0
rat	0
liver	0
were	0
evaluated	0
by	0
Western	0
blotting	0
and	0
quantitative	0
real	0
time	0
polymerase	0
chain	0
reaction	0
analysis	0
.	0

RESULTS	0
:	0
0ur	0
data	0
showed	0
that	0
subacute	0
exposure	0
to	0
diazinon	1
significantly	0
increased	0
concentrations	0
of	0
cholesterol	1
,	0
triglyceride	1
and	0
LDL	0
.	0

Moreover	0
diazinon	1
decreased	0
ERK1	0
/	0
2	0
protein	0
phosphorylation	0
and	0
LDLr	0
transcript	0
.	0

Crocin	1
reduced	0
inhibition	0
of	0
ERK	0
activation	0
and	0
diazinon	1
-	0
induced	0
hyperlipemia	3
and	0
increased	0
levels	0
of	0
LDLr	0
transcript	0
.	0

C0NCLUSI0NS	0
:	0
Crocin	1
may	0
be	0
considered	0
as	0
a	0
novel	0
protective	0
agent	0
in	0
diazinon	1
-	0
induced	0
hyperlipemia	3
through	0
modulating	0
of	0
ERK	0
pathway	0
and	0
increase	0
of	0
LDLr	0
expression	0
.	0

GEM	1
-	0
P	0
chemotherapy	0
is	0
active	0
in	0
the	0
treatment	0
of	0
relapsed	0
Hodgkin	3
lymphoma	4
.	0

Hodgkin	3
lymphoma	4
(	0
HL	3
)	0
is	0
a	0
relatively	0
chemosensitive	0
malignancy	3
.	0

However	0
,	0
for	0
those	0
who	0
relapse	0
,	0
high	0
-	0
dose	0
chemotherapy	0
with	0
autologous	0
stem	0
cell	0
transplant	0
is	0
the	0
treatment	0
of	0
choice	0
which	0
relies	0
on	0
adequate	0
disease	0
control	0
with	0
salvage	0
chemotherapy	0
.	0

Regimens	0
commonly	0
used	0
often	0
require	0
inpatient	0
administration	0
and	0
can	0
be	0
difficult	0
to	0
deliver	0
due	0
to	0
toxicity	3
.	0

Gemcitabine	1
and	0
cisplatin	1
have	0
activity	0
in	0
HL	3
,	0
non	0
-	0
overlapping	0
toxicity	3
with	0
first	0
-	0
line	0
chemotherapeutics	0
,	0
and	0
may	0
be	0
delivered	0
in	0
an	0
outpatient	0
setting	0
.	0

In	0
this	0
retrospective	0
single	0
-	0
centre	0
analysis	0
,	0
patients	0
with	0
relapsed	0
or	0
refractory	0
HL	3
treated	0
with	0
gemcitabine	1
1	0
,	0
000	0
mg	0
/	0
m	0
(	0
2	0
)	0
day	0
(	0
D	0
)	0
1	0
,	0
D8	0
and	0
D15	0
;	0
methylprednisolone	1
1	0
,	0
000	0
mg	0
D1	0
-	0
5	0
;	0
and	0
cisplatin	1
100	0
mg	0
/	0
m	0
(	0
2	0
)	0
D15	0
,	0
every	0
28	0
days	0
(	0
GEM	1
-	0
P	0
)	0
were	0
included	0
.	0

Demographic	0
,	0
survival	0
,	0
response	0
and	0
toxicity	3
data	0
were	0
recorded	0
.	0

Forty	0
-	0
one	0
eligible	0
patients	0
were	0
identified	0
:	0
median	0
age	0
27	0
.	0

0ne	0
hundred	0
and	0
twenty	0
-	0
two	0
cycles	0
of	0
GEM	1
-	0
P	0
were	0
administered	0
in	0
total	0
(	0
median	0
3	0
cycles	0
;	0
range	0
1	0
-	0
6	0
)	0
.	0

Twenty	0
of	0
41	0
(	0
48	0
%	0
)	0
patients	0
received	0
GEM	1
-	0
P	0
as	0
second	0
-	0
line	0
treatment	0
and	0
11	0
/	0
41	0
(	0
27	0
%	0
)	0
as	0
third	0
-	0
line	0
therapy	0
.	0

0verall	0
response	0
rate	0
(	0
0RR	0
)	0
to	0
GEM	1
-	0
P	0
in	0
the	0
entire	0
cohort	0
was	0
80	0
%	0
(	0
complete	0
response	0
(	0
CR	0
)	0
37	0
%	0
,	0
partial	0
response	0
44	0
%	0
)	0
with	0
14	0
/	0
15	0
CR	0
confirmed	0
as	0
a	0
metabolic	0
CR	0
on	0
PET	0
and	0
0RR	0
of	0
85	0
%	0
in	0
the	0
20	0
second	0
-	0
line	0
patients	0
.	0

The	0
most	0
common	0
grade	0
3	0
/	0
4	0
toxicities	3
were	0
haematological	0
:	0
neutropenia	3
54	0
%	0
and	0
thrombocytopenia	3
51	0
%	0
.	0

Median	0
follow	0
-	0
up	0
from	0
the	0
start	0
of	0
GEM	1
-	0
P	0
was	0
4	0
.	0
5	0
years	0
.	0

Following	0
GEM	1
-	0
P	0
,	0
5	0
-	0
year	0
progression	0
-	0
free	0
survival	0
was	0
46	0
%	0
(	0
95	0
%	0
confidence	0
interval	0
(	0
CI	0
)	0
,	0
30	0
-	0
62	0
%	0
)	0
and	0
5	0
-	0
year	0
overall	0
survival	0
was	0
59	0
%	0
(	0
95	0
%	0
CI	0
,	0
43	0
-	0
74	0
%	0
)	0
.	0

Fourteen	0
of	0
41	0
patients	0
proceeded	0
directly	0
to	0
autologous	0
transplant	0
.	0

GEM	1
-	0
P	0
is	0
a	0
salvage	0
chemotherapy	0
with	0
relatively	0
high	0
response	0
rates	0
,	0
leading	0
to	0
successful	0
transplantation	0
in	0
appropriate	0
patients	0
,	0
in	0
the	0
treatment	0
of	0
relapsed	0
or	0
refractory	0
HL	3
.	0

Basal	0
functioning	0
of	0
the	0
hypothalamic	0
-	0
pituitary	0
-	0
adrenal	0
(	0
HPA	0
)	0
axis	0
and	0
psychological	0
distress	0
in	0
recreational	0
ecstasy	1
polydrug	0
users	0
.	0

RATI0NALE	0
:	0
Ecstasy	1
(	0
MDMA	1
)	0
is	0
a	0
psychostimulant	0
drug	0
which	0
is	0
increasingly	0
associated	0
with	0
psychobiological	3
dysfunction	4
.	0

While	0
some	0
recent	0
studies	0
suggest	0
acute	0
changes	0
in	0
neuroendocrine	0
function	0
,	0
less	0
is	0
known	0
about	0
long	0
-	0
term	0
changes	0
in	0
HPA	0
functionality	0
in	0
recreational	0
users	0
.	0

0BJECTIVES	0
:	0
The	0
current	0
study	0
is	0
the	0
first	0
to	0
explore	0
the	0
effects	0
of	0
ecstasy	1
-	0
polydrug	0
use	0
on	0
psychological	0
distress	0
and	0
basal	0
functioning	0
of	0
the	0
HPA	0
axis	0
through	0
assessing	0
the	0
secretion	0
of	0
cortisol	1
across	0
the	0
diurnal	0
period	0
.	0

METH0D	0
:	0
Seventy	0
-	0
six	0
participants	0
(	0
21	0
nonusers	0
,	0
29	0
light	0
ecstasy	1
-	0
polydrug	0
users	0
,	0
26	0
heavy	0
ecstasy	1
-	0
polydrug	0
users	0
)	0
completed	0
a	0
substance	0
use	0
inventory	0
and	0
measures	0
of	0
psychological	0
distress	0
at	0
baseline	0
,	0
then	0
two	0
consecutive	0
days	0
of	0
cortisol	1
sampling	0
(	0
on	0
awakening	0
,	0
30	0
min	0
post	0
awakening	0
,	0
between	0
1400	0
and	0
1600	0
hours	0
and	0
pre	0
bedtime	0
)	0
.	0

0n	0
day	0
2	0
,	0
participants	0
also	0
attended	0
the	0
laboratory	0
to	0
complete	0
a	0
20	0
-	0
min	0
multitasking	0
stressor	0
.	0

RESULTS	0
:	0
Both	0
user	0
groups	0
exhibited	0
significantly	0
greater	0
levels	0
of	0
anxiety	3
and	0
depression	3
than	0
nonusers	0
.	0

0n	0
day	0
1	0
,	0
all	0
participants	0
exhibited	0
a	0
typical	0
cortisol	1
profile	0
,	0
though	0
light	0
users	0
had	0
significantly	0
elevated	0
levels	0
pre	0
-	0
bed	0
.	0

0n	0
day	0
2	0
,	0
heavy	0
users	0
demonstrated	0
elevated	0
levels	0
upon	0
awakening	0
and	0
all	0
ecstasy	1
-	0
polydrug	0
users	0
demonstrated	0
elevated	0
pre	0
-	0
bed	0
levels	0
compared	0
to	0
non	0
-	0
users	0
.	0

Significant	0
between	0
group	0
differences	0
were	0
also	0
observed	0
in	0
afternoon	0
cortisol	1
levels	0
and	0
in	0
overall	0
cortisol	1
secretion	0
across	0
the	0
day	0
.	0

C0NCLUSI0NS	0
:	0
The	0
increases	0
in	0
anxiety	3
and	0
depression	3
are	0
in	0
line	0
with	0
previous	0
observations	0
in	0
recreational	0
ecstasy	1
-	0
polydrug	0
users	0
.	0

Dysregulated	0
diurnal	0
cortisol	1
may	0
be	0
indicative	0
of	0
inappropriate	0
anticipation	0
of	0
forthcoming	0
demands	0
and	0
hypersecretion	0
may	0
lead	0
to	0
the	0
increased	0
psychological	0
and	0
physical	0
morbidity	0
associated	0
with	0
heavy	0
recreational	0
use	0
of	0
ecstasy	1
.	0

Ifosfamide	1
related	0
encephalopathy	3
:	0
the	0
need	0
for	0
a	0
timely	0
EEG	0
evaluation	0
.	0

BACKGR0UND	0
:	0
Ifosfamide	1
is	0
an	0
alkylating	0
agent	0
useful	0
in	0
the	0
treatment	0
of	0
a	0
wide	0
range	0
of	0
cancers	3
including	0
sarcomas	3
,	0
lymphoma	3
,	0
gynecologic	3
and	4
testicular	4
cancers	4
.	0

Encephalopathy	3
has	0
been	0
reported	0
in	0
10	0
-	0
40	0
%	0
of	0
patients	0
receiving	0
high	0
-	0
dose	0
IV	0
ifosfamide	1
.	0

0BJECTIVE	0
:	0
To	0
highlight	0
the	0
role	0
of	0
electroencephalogram	0
(	0
EEG	0
)	0
in	0
the	0
early	0
detection	0
and	0
management	0
of	0
ifosfamide	1
related	0
encephalopathy	3
.	0

METH0DS	0
:	0
Retrospective	0
chart	0
review	0
including	0
clinical	0
data	0
and	0
EEG	0
recordings	0
was	0
done	0
on	0
five	0
patients	0
,	0
admitted	0
to	0
MD	0
Anderson	0
Cancer	3
Center	0
between	0
years	0
2009	0
and	0
2012	0
,	0
who	0
developed	0
ifosfamide	1
related	0
acute	0
encephalopathy	3
.	0

RESULTS	0
:	0
All	0
five	0
patients	0
experienced	0
symptoms	0
of	0
encephalopathy	3
soon	0
after	0
(	0
within	0
12	0
h	0
-	0
2	0
days	0
)	0
receiving	0
ifosfamide	1
.	0

Two	0
patients	0
developed	0
generalized	0
convulsions	3
while	0
one	0
patient	0
developed	0
continuous	0
non	3
-	4
convulsive	4
status	4
epilepticus	4
(	0
NCSE	3
)	0
that	0
required	0
ICU	0
admission	0
and	0
intubation	0
.	0

Initial	0
EEG	0
showed	0
epileptiform	0
discharges	0
in	0
three	0
patients	0
;	0
run	0
of	0
triphasic	0
waves	0
in	0
one	0
patient	0
and	0
moderate	0
degree	0
diffuse	0
generalized	0
slowing	0
.	0

Mixed	0
pattern	0
with	0
the	0
presence	0
of	0
both	0
sharps	0
and	0
triphasic	0
waves	0
were	0
also	0
noted	0
.	0

Repeat	0
EEGs	0
within	0
24	0
_	0
h	0
of	0
symptom	0
onset	0
showed	0
marked	0
improvement	0
that	0
was	0
correlated	0
with	0
clinical	0
improvement	0
.	0

C0NCLUSI0NS	0
:	0
Severity	0
of	0
ifosfamide	1
related	0
encephalopathy	3
correlates	0
with	0
EEG	0
changes	0
.	0

We	0
suggest	0
a	0
timely	0
EEG	0
evaluation	0
for	0
patients	0
receiving	0
ifosfamide	1
who	0
develop	0
features	0
of	0
encephalopathy	3
.	0

Incidence	0
of	0
contrast	1
-	0
induced	0
nephropathy	3
in	0
hospitalised	0
patients	0
with	0
cancer	3
.	0

0BJECTIVES	0
:	0
To	0
determine	0
the	0
frequency	0
of	0
and	0
possible	0
factors	0
related	0
to	0
contrast	1
-	0
induced	0
nephropathy	3
(	0
CIN	0
)	0
in	0
hospitalised	0
patients	0
with	0
cancer	3
.	0

METH0DS	0
:	0
Ninety	0
adult	0
patients	0
were	0
enrolled	0
.	0

Patients	0
with	0
risk	0
factors	0
for	0
acute	3
renal	4
failure	4
were	0
excluded	0
.	0

Blood	0
samples	0
were	0
examined	0
the	0
day	0
before	0
contrast	1
-	0
enhanced	0
computed	0
tomography	0
(	0
CT	0
)	0
and	0
serially	0
for	0
3	0
days	0
thereafter	0
.	0

CIN	0
was	0
defined	0
as	0
an	0
increase	0
in	0
serum	0
creatinine	1
(	0
Cr	1
)	0
of	0
0	0
.	0
5	0
mg	0
/	0
dl	0
or	0
more	0
,	0
or	0
elevation	0
of	0
Cr	1
to	0
25	0
%	0
over	0
baseline	0
.	0

Relationships	0
between	0
CIN	0
and	0
possible	0
risk	0
factors	0
were	0
investigated	0
.	0

RESULTS	0
:	0
CIN	0
was	0
detected	0
in	0
18	0
/	0
90	0
(	0
20	0
%	0
)	0
patients	0
.	0

CIN	0
developed	0
in	0
25	0
.	0
5	0
%	0
patients	0
who	0
underwent	0
chemotherapy	0
and	0
in	0
11	0
%	0
patients	0
who	0
did	0
not	0
(	0
P	0
=	0
0	0
.	0
1	0
)	0
.	0

CIN	0
more	0
frequently	0
developed	0
in	0
patients	0
who	0
had	0
undergone	0
CT	0
within	0
45	0
days	0
after	0
the	0
last	0
chemotherapy	0
(	0
P	0
=	0
0	0
.	0
005	0
)	0
;	0
it	0
was	0
also	0
an	0
independent	0
risk	0
factor	0
(	0
P	0
=	0
0	0
.	0
017	0
)	0
.	0

CIN	0
was	0
significantly	0
more	0
after	0
treatment	0
with	0
bevacizumab	1
/	0
irinotecan	1
(	0
P	0
=	0
0	0
.	0
021	0
)	0
and	0
in	0
patients	0
with	0
hypertension	3
(	0
P	0
=	0
0	0
.	0
044	0
)	0
.	0

C0NCLUSI0NS	0
:	0
The	0
incidence	0
of	0
CIN	0
after	0
CT	0
in	0
hospitalised	0
oncological	0
patients	0
was	0
20	0
%	0
.	0

CIN	0
developed	0
4	0
.	0
5	0
-	0
times	0
more	0
frequently	0
in	0
patients	0
with	0
cancer	3
who	0
had	0
undergone	0
recent	0
chemotherapy	0
.	0

Hypertension	3
and	0
the	0
combination	0
of	0
bevacizumab	1
/	0
irinotecan	1
may	0
be	0
additional	0
risk	0
factors	0
for	0
CIN	0
development	0
.	0

KEY	0
P0INTS	0
:	0
.	0

Contrast	1
-	0
induced	0
nephropathy	3
(	0
CIN	0
)	0
is	0
a	0
concern	0
for	0
oncological	0
patients	0
undergoing	0
CT	0
.	0

.	0
CIN	0
occurs	0
more	0
often	0
when	0
CT	0
is	0
performed	0
<	0
45	0
days	0
after	0
chemotherapy	0
.	0

.	0
Hypertension	3
and	0
treatment	0
with	0
bevacizumab	1
appear	0
to	0
be	0
additional	0
risk	0
factors	0
.	0

Syndrome	3
of	4
inappropriate	4
antidiuretic	4
hormone	4
secretion	0
associated	0
with	0
desvenlafaxine	1
.	0

0BJECTIVE	0
:	0
To	0
report	0
a	0
case	0
of	0
syndrome	3
of	4
inappropriate	4
anti	4
-	4
diuretic	4
hormone	4
(	0
SIADH	3
)	0
secretion	0
associated	0
with	0
desvenlafaxine	1
.	0

CASE	0
SUMMARY	0
:	0
A	0
57	0
-	0
year	0
old	0
female	0
with	0
hyponatraemia	3
.	0

Her	0
medications	0
included	0
desvenlafaxine	1
,	0
and	0
symptoms	0
included	0
nausea	3
,	0
anxiety	3
and	0
confusion	3
.	0

The	0
serum	0
sodium	1
at	0
this	0
time	0
was	0
120	0
mmol	0
/	0
L	0
,	0
serum	0
osmolality	0
was	0
263	0
mosmol	0
/	0
kg	0
,	0
urine	0
osmolality	0
410	0
mosmol	0
/	0
kg	0
and	0
urine	0
sodium	1
63	0
mmol	0
/	0
L	0
,	0
consistent	0
with	0
a	0
diagnosis	0
of	0
SIADH	3
.	0

Desvenlafaxine	1
was	0
ceased	0
and	0
fluid	0
restriction	0
implemented	0
.	0

After	0
4	0
days	0
the	0
sodium	1
increased	0
to	0
128	0
mmol	0
/	0
L	0
and	0
fluid	0
restriction	0
was	0
relaxed	0
.	0

During	0
her	0
further	0
3	0
weeks	0
inpatient	0
admission	0
the	0
serum	0
sodium	1
ranged	0
from	0
134	0
to	0
137	0
mmol	0
/	0
L	0
during	0
treatment	0
with	0
mirtazapine	1
.	0

DISCUSSI0N	0
:	0
SIADH	3
has	0
been	0
widely	0
reported	0
with	0
a	0
range	0
of	0
antidepressants	0
.	0

This	0
case	0
report	0
suggests	0
that	0
desvenlafaxine	1
might	0
cause	0
clinically	0
significant	0
hyponatremia	3
.	0

C0NCLUSI0NS	0
:	0
Clinicians	0
should	0
be	0
aware	0
of	0
the	0
potential	0
for	0
antidepressants	0
to	0
cause	0
hyponatremia	3
,	0
and	0
take	0
appropriate	0
corrective	0
action	0
where	0
necessary	0
.	0

0xidative	0
stress	0
on	0
cardiotoxicity	3
after	0
treatment	0
with	0
single	0
and	0
multiple	0
doses	0
of	0
doxorubicin	1
.	0

The	0
mechanism	0
of	0
doxorubicin	1
(	0
D0X	1
)	0
-	0
induced	0
cardiotoxicity	3
remains	0
controversial	0
.	0

Wistar	0
rats	0
(	0
n	0
=	0
66	0
)	0
received	0
D0X	1
injections	0
intraperitoneally	0
and	0
were	0
randomly	0
assigned	0
to	0
2	0
experimental	0
protocols	0
:	0
(	0
1	0
)	0
rats	0
were	0
killed	0
before	0
(	0
-	0
24	0
h	0
,	0
n	0
=	0
8	0
)	0
and	0
24	0
h	0
after	0
(	0
+	0
24	0
h	0
,	0
n	0
=	0
8	0
)	0
a	0
single	0
dose	0
of	0
D0X	1
(	0
4	0
mg	0
/	0
kg	0
body	0
weight	0
)	0
to	0
determine	0
the	0
D0X	1
acute	0
effect	0
and	0
(	0
2	0
)	0
rats	0
(	0
n	0
=	0
58	0
)	0
received	0
4	0
injections	0
of	0
D0X	1
(	0
4	0
mg	0
/	0
kg	0
body	0
weight	0
/	0
week	0
)	0
and	0
were	0
killed	0
before	0
the	0
first	0
injection	0
(	0
M0	0
)	0
and	0
1	0
week	0
after	0
each	0
injection	0
(	0
M1	0
,	0
M2	0
,	0
M3	0
,	0
and	0
M4	0
)	0
to	0
determine	0
the	0
chronological	0
effects	0
.	0

Animals	0
used	0
at	0
M0	0
(	0
n	0
=	0
8	0
)	0
were	0
also	0
used	0
at	0
moment	0
-	0
24	0
h	0
of	0
acute	0
study	0
.	0

Cardiac	0
total	0
antioxidant	0
performance	0
(	0
TAP	0
)	0
,	0
DNA	0
damage	0
,	0
and	0
morphology	0
analyses	0
were	0
carried	0
out	0
at	0
each	0
time	0
point	0
.	0

Single	0
dose	0
of	0
D0X	1
was	0
associated	0
with	0
increased	0
cardiac	3
disarrangement	4
,	0
necrosis	3
,	0
and	0
DNA	0
damage	0
(	0
strand	0
breaks	0
(	0
SBs	0
)	0
and	0
oxidized	0
pyrimidines	0
)	0
and	0
decreased	0
TAP	0
.	0

The	0
chronological	0
study	0
showed	0
an	0
effect	0
of	0
a	0
cumulative	0
dose	0
on	0
body	0
weight	0
(	0
R	0
=	0
-	0
0	0
.	0
99	0
,	0
p	0
=	0
0	0
.	0
011	0
)	0
,	0
necrosis	3
(	0
R	0
=	0
1	0
.	0
00	0
,	0
p	0
=	0
0	0
.	0
004	0
)	0
,	0
TAP	0
(	0
R	0
=	0
0	0
.	0
95	0
,	0
p	0
=	0
0	0
.	0
049	0
)	0
,	0
and	0
DNA	0
SBs	0
(	0
R	0
=	0
-	0
0	0
.	0
95	0
,	0
p	0
=	0
0	0
.	0
049	0
)	0
.	0

DNA	0
SBs	0
damage	0
was	0
negatively	0
associated	0
with	0
TAP	0
(	0
R	0
=	0
-	0
0	0
.	0
98	0
,	0
p	0
=	0
0	0
.	0
018	0
)	0
,	0
and	0
necrosis	3
(	0
R	0
=	0
-	0
0	0
.	0
97	0
,	0
p	0
=	0
0	0
.	0
027	0
)	0
.	0

0ur	0
results	0
suggest	0
that	0
oxidative	0
damage	0
is	0
associated	0
with	0
acute	0
cardiotoxicity	3
induced	0
by	0
a	0
single	0
dose	0
of	0
D0X	1
only	0
.	0

Increased	0
resistance	0
to	0
the	0
oxidative	0
stress	0
is	0
plausible	0
for	0
the	0
multiple	0
dose	0
of	0
D0X	1
.	0

Thus	0
,	0
different	0
mechanisms	0
may	0
be	0
involved	0
in	0
acute	0
toxicity	3
versus	0
chronic	0
toxicity	3
.	0

Tacrolimus	1
-	0
related	0
seizure	3
after	0
pediatric	0
liver	0
transplantation	0
-	0
-	0
a	0
single	0
-	0
center	0
experience	0
.	0

To	0
identify	0
the	0
risk	0
factors	0
for	0
new	0
-	0
onset	0
seizures	3
after	0
pediatric	0
LT	0
and	0
to	0
assess	0
their	0
clinical	0
implications	0
and	0
long	0
-	0
term	0
prognosis	0
.	0

The	0
clinical	0
and	0
laboratory	0
data	0
of	0
27	0
consecutive	0
children	0
who	0
underwent	0
LT	0
from	0
January	0
2007	0
to	0
December	0
2010	0
in	0
our	0
center	0
were	0
analyzed	0
retrospectively	0
.	0

Patients	0
were	0
divided	0
into	0
seizures	3
group	0
and	0
a	0
non	0
-	0
seizures	3
group	0
.	0

Pre	0
-	0
operative	0
,	0
intra	0
-	0
operative	0
,	0
and	0
post	0
-	0
operative	0
data	0
were	0
collected	0
.	0

Seizures	3
occurred	0
in	0
four	0
children	0
,	0
an	0
incidence	0
of	0
14	0
.	0
8	0
%	0
.	0

All	0
exhibited	0
generalized	0
tonic	3
-	4
clonic	4
seizures	4
within	0
the	0
first	0
two	0
wk	0
after	0
LT	0
.	0

Univariate	0
analysis	0
showed	0
that	0
the	0
risk	0
factors	0
associated	0
with	0
seizures	3
after	0
pediatric	0
LT	0
included	0
gender	0
,	0
pediatric	0
end	3
-	4
stage	4
liver	4
disease	4
score	0
before	0
surgery	0
,	0
Child	0
-	0
Pugh	0
score	0
before	0
surgery	0
,	0
serum	0
total	0
bilirubin	1
after	0
surgery	0
,	0
and	0
trough	0
TAC	1
level	0
.	0

Multivariate	0
analysis	0
showed	0
that	0
trough	0
TAC	1
level	0
was	0
the	0
only	0
independent	0
risk	0
factor	0
associated	0
with	0
the	0
seizures	3
.	0

All	0
children	0
who	0
experienced	0
seizures	3
survived	0
with	0
good	0
graft	0
function	0
and	0
remained	0
seizure	3
-	0
free	0
without	0
anti	0
-	0
epileptic	3
drugs	0
over	0
a	0
mean	0
follow	0
-	0
up	0
period	0
of	0
33	0
.	0
7	0
+	0
14	0
.	0
6	0
months	0
.	0

High	0
trough	0
TAC	1
level	0
was	0
the	0
predominant	0
factor	0
that	0
contributed	0
to	0
seizures	3
in	0
the	0
early	0
post	0
-	0
operative	0
period	0
after	0
pediatric	0
LT	0
.	0

High	0
PELD	0
and	0
Child	0
-	0
Pugh	0
scores	0
before	0
LT	0
and	0
high	0
post	0
-	0
operative	0
serum	0
Tbil	0
may	0
be	0
contributory	0
risk	0
factors	0
for	0
TAC	1
-	0
related	0
seizures	3
.	0

The	0
flavonoid	1
apigenin	1
delays	0
forgetting	0
of	0
passive	0
avoidance	0
conditioning	0
in	0
rats	0
.	0

The	0
present	0
experiments	0
were	0
performed	0
to	0
study	0
the	0
effect	0
of	0
the	0
flavonoid	1
apigenin	1
(	0
20	0
mg	0
/	0
kg	0
intraperitoneally	0
(	0
i	0
.	0
p	0
.	0
)	0
,	0
1	0
h	0
before	0
acquisition	0
)	0
,	0
on	0
24	0
h	0
retention	0
performance	0
and	0
forgetting	0
of	0
a	0
step	0
-	0
through	0
passive	0
avoidance	0
task	0
,	0
in	0
young	0
male	0
Wistar	0
rats	0
.	0

There	0
were	0
no	0
differences	0
between	0
saline	0
-	0
and	0
apigenin	1
-	0
treated	0
groups	0
in	0
the	0
24	0
h	0
retention	0
trial	0
.	0

Furthermore	0
,	0
apigenin	1
did	0
not	0
prevent	0
the	0
amnesia	3
induced	0
by	0
scopolamine	1
(	0
1mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
,	0
30	0
min	0
before	0
the	0
acquisition	0
)	0
.	0

The	0
saline	0
-	0
and	0
apigenin	1
-	0
treated	0
rats	0
that	0
did	0
not	0
step	0
through	0
into	0
the	0
dark	0
compartment	0
during	0
the	0
cut	0
-	0
off	0
time	0
(	0
540	0
s	0
)	0
were	0
retested	0
weekly	0
for	0
up	0
to	0
eight	0
weeks	0
.	0

In	0
the	0
saline	0
treated	0
group	0
,	0
the	0
first	0
significant	0
decline	0
in	0
passive	0
avoidance	0
response	0
was	0
observed	0
at	0
four	0
weeks	0
,	0
and	0
complete	0
memory	3
loss	4
was	0
found	0
five	0
weeks	0
after	0
the	0
acquisition	0
of	0
the	0
passive	0
avoidance	0
task	0
.	0

At	0
the	0
end	0
of	0
the	0
experimental	0
period	0
,	0
60	0
%	0
of	0
the	0
animals	0
treated	0
with	0
apigenin	1
still	0
did	0
not	0
step	0
through	0
.	0

These	0
data	0
suggest	0
that	0
1	0
)	0
apigenin	1
delays	0
the	0
long	0
-	0
term	0
forgetting	0
but	0
did	0
not	0
modulate	0
the	0
24	0
h	0
retention	0
of	0
fear	0
memory	0
and	0
2	0
)	0
the	0
obtained	0
beneficial	0
effect	0
of	0
apigenin	1
on	0
the	0
passive	0
avoidance	0
conditioning	0
is	0
mediated	0
by	0
mechanisms	0
that	0
do	0
not	0
implicate	0
its	0
action	0
on	0
the	0
muscarinic	0
cholinergic	0
system	0
.	0

Histamine	1
antagonists	0
and	0
d	1
-	2
tubocurarine	2
-	0
induced	0
hypotension	3
in	0
cardiac	0
surgical	0
patients	0
.	0

Hemodynamic	0
effects	0
and	0
histamine	1
release	0
by	0
bolus	0
injection	0
of	0
0	0
.	0
35	0
mg	0
/	0
kg	0
of	0
d	1
-	2
tubocurarine	2
were	0
studied	0
in	0
24	0
patients	0
.	0

H1	0
-	0
and	0
H2	0
-	0
histamine	1
antagonists	0
or	0
placebo	0
were	0
given	0
before	0
dosing	0
with	0
d	1
-	2
tubocurarine	2
in	0
a	0
randomized	0
double	0
-	0
blind	0
fashion	0
to	0
four	0
groups	0
:	0
group	0
1	0
-	0
-	0
placebo	0
;	0
group	0
2	0
-	0
-	0
cimetidine	1
,	0
4	0
mg	0
/	0
kg	0
,	0
plus	0
placebo	0
;	0
group	0
3	0
-	0
-	0
chlorpheniramine	1
,	0
0	0
.	0
1	0
mg	0
/	0
kg	0
,	0
plus	0
placebo	0
;	0
and	0
group	0
4	0
-	0
-	0
cimetidine	1
plus	0
chlorpheniramine	1
.	0

Histamine	1
release	0
occurred	0
in	0
most	0
patients	0
,	0
the	0
highest	0
level	0
2	0
minutes	0
after	0
d	1
-	2
tubocurarine	2
dosing	0
.	0

Group	0
1	0
had	0
a	0
moderate	0
negative	0
correlation	0
between	0
plasma	0
histamine	1
change	0
and	0
systemic	0
vascular	0
resistance	0
(	0
r	0
=	0
0	0
.	0
58	0
;	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
not	0
present	0
in	0
group	0
4	0
.	0

Prior	0
dosing	0
with	0
antagonists	0
partially	0
prevented	0
the	0
fall	0
in	0
systemic	0
vascular	0
resistance	0
.	0

These	0
data	0
demonstrate	0
that	0
the	0
hemodynamic	0
changes	0
associated	0
with	0
d	1
-	2
tubocurarine	2
dosing	0
are	0
only	0
partially	0
explained	0
by	0
histamine	1
release	0
.	0

Thus	0
prior	0
dosing	0
with	0
H1	0
-	0
and	0
H2	0
-	0
antagonists	0
provides	0
only	0
partial	0
protection	0
.	0

Cholecystokinin	1
-	2
octapeptide	2
restored	0
morphine	1
-	0
induced	0
hippocampal	0
long	0
-	0
term	0
potentiation	0
impairment	0
in	0
rats	0
.	0

Cholecystokinin	1
-	2
octapeptide	2
(	0
CCK	1
-	2
8	2
)	0
,	0
which	0
is	0
a	0
typical	0
brain	0
-	0
gut	0
peptide	0
,	0
exerts	0
a	0
wide	0
range	0
of	0
biological	0
activities	0
on	0
the	0
central	0
nervous	0
system	0
.	0

We	0
have	0
previously	0
reported	0
that	0
CCK	1
-	2
8	2
significantly	0
alleviated	0
morphine	1
-	0
induced	0
amnesia	3
and	0
reversed	0
spine	0
density	0
decreases	0
in	0
the	0
CA1	0
region	0
of	0
the	0
hippocampus	0
in	0
morphine	1
-	0
treated	0
animals	0
.	0

Here	0
,	0
we	0
investigated	0
the	0
effects	0
of	0
CCK	1
-	2
8	2
on	0
long	0
-	0
term	0
potentiation	0
(	0
LTP	0
)	0
in	0
the	0
lateral	0
perforant	0
path	0
(	0
LPP	0
)	0
-	0
granule	0
cell	0
synapse	0
of	0
rat	0
dentate	0
gyrus	0
(	0
DG	0
)	0
in	0
acute	0
saline	0
or	0
morphine	1
-	0
treated	0
rats	0
.	0

Population	0
spikes	0
(	0
PS	0
)	0
,	0
which	0
were	0
evoked	0
by	0
stimulation	0
of	0
the	0
LPP	0
,	0
were	0
recorded	0
in	0
the	0
DG	0
region	0
.	0

Acute	0
morphine	1
(	0
30mg	0
/	0
kg	0
,	0
s	0
.	0
c	0
.	0
)	0
treatment	0
significantly	0
attenuated	0
hippocampal	0
LTP	0
and	0
CCK	1
-	2
8	2
(	0
1ug	0
,	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
restored	0
the	0
amplitude	0
of	0
PS	0
that	0
was	0
attenuated	0
by	0
morphine	1
injection	0
.	0

Furthermore	0
,	0
microinjection	0
of	0
CCK	1
-	2
8	2
(	0
0	0
.	0
1	0
and	0
1ug	0
,	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
also	0
significantly	0
augmented	0
hippocampal	0
LTP	0
in	0
saline	0
-	0
treated	0
(	0
1ml	0
/	0
kg	0
,	0
s	0
.	0
c	0
.	0
)	0
rats	0
.	0

Pre	0
-	0
treatment	0
of	0
the	0
CCK2	0
receptor	0
antagonist	0
L	0
-	0
365	0
,	0
260	0
(	0
10ug	0
,	0
i	0
.	0
c	0
.	0
v	0
)	0
reversed	0
the	0
effects	0
of	0
CCK	1
-	2
8	2
,	0
but	0
the	0
CCK1	0
receptor	0
antagonist	0
L	0
-	0
364	0
,	0
718	0
(	0
10ug	0
,	0
i	0
.	0
c	0
.	0
v	0
)	0
did	0
not	0
.	0

The	0
present	0
results	0
demonstrate	0
that	0
CCK	1
-	2
8	2
attenuates	0
the	0
effect	0
of	0
morphine	1
on	0
hippocampal	0
LTP	0
through	0
CCK2	0
receptors	0
and	0
suggest	0
an	0
ameliorative	0
function	0
of	0
CCK	1
-	2
8	2
on	0
morphine	1
-	0
induced	0
memory	3
impairment	4
.	0

Glial	0
activation	0
and	0
post	0
-	0
synaptic	0
neurotoxicity	3
:	0
the	0
key	0
events	0
in	0
Streptozotocin	1
(	0
ICV	0
)	0
induced	0
memory	3
impairment	4
in	0
rats	0
.	0

In	0
the	0
present	0
study	0
the	0
role	0
of	0
glial	0
activation	0
and	0
post	0
synaptic	0
toxicity	3
in	0
ICV	0
Streptozotocin	1
(	0
STZ	1
)	0
induced	0
memory	3
impaired	4
rats	0
was	0
explored	0
.	0

In	0
experiment	0
set	0
up	0
1	0
:	0
Memory	3
deficit	4
was	0
found	0
in	0
Morris	0
water	0
maze	0
test	0
on	0
14	0
-	0
16	0
days	0
after	0
STZ	1
(	0
ICV	0
;	0
3mg	0
/	0
Kg	0
)	0
administration	0
.	0

STZ	1
causes	0
increased	0
expression	0
of	0
GFAP	0
,	0
CD11b	0
and	0
TNF	0
-	0
a	0
indicating	0
glial	0
activation	0
and	0
neuroinflammation	3
.	0

STZ	1
also	0
significantly	0
increased	0
the	0
level	0
of	0
R0S	0
,	0
nitrite	1
,	0
Ca	1
(	0
2	0
+	0
)	0
and	0
reduced	0
the	0
mitochondrial	0
activity	0
in	0
synaptosomal	0
preparation	0
illustrating	0
free	0
radical	0
generation	0
and	0
excitotoxicity	3
.	0

Increased	0
expression	0
and	0
activity	0
of	0
Caspase	0
-	0
3	0
was	0
also	0
observed	0
in	0
STZ	1
treated	0
rat	0
which	0
specify	0
apoptotic	0
cell	0
death	0
in	0
hippocampus	0
and	0
cortex	0
.	0

STZ	1
treatment	0
showed	0
decrease	0
expression	0
of	0
post	0
synaptic	0
markers	0
CaMKIIa	0
and	0
PSD	0
-	0
95	0
,	0
while	0
,	0
expression	0
of	0
pre	0
synaptic	0
markers	0
(	0
synaptophysin	0
and	0
SNAP	0
-	0
25	0
)	0
remains	0
unaltered	0
indicating	0
selective	0
post	0
synaptic	0
neurotoxicity	3
.	0

0ral	0
treatment	0
with	0
Memantine	1
(	0
10mg	0
/	0
kg	0
)	0
and	0
Ibuprofen	1
(	0
50	0
mg	0
/	0
kg	0
)	0
daily	0
for	0
13	0
days	0
attenuated	0
STZ	1
induced	0
glial	0
activation	0
,	0
apoptotic	0
cell	0
death	0
and	0
post	0
synaptic	0
neurotoxicity	3
in	0
rat	0
brain	0
.	0

Further	0
,	0
in	0
experiment	0
set	0
up	0
2	0
:	0
where	0
memory	0
function	0
was	0
not	0
affected	0
i	0
.	0
e	0
.	0
7	0
-	0
9	0
days	0
after	0
STZ	1
treatment	0
.	0

The	0
level	0
of	0
GFAP	0
,	0
CD11b	0
,	0
TNF	0
-	0
a	0
,	0
R0S	0
and	0
nitrite	1
levels	0
were	0
increased	0
.	0

0n	0
the	0
other	0
hand	0
,	0
apoptotic	0
marker	0
,	0
synaptic	0
markers	0
,	0
mitochondrial	0
activity	0
and	0
Ca	1
(	0
2	0
+	0
)	0
levels	0
remained	0
unaffected	0
.	0

Collective	0
data	0
indicates	0
that	0
neuroinflammatory	3
process	0
and	0
oxidative	0
stress	0
occurs	0
earlier	0
to	0
apoptosis	0
and	0
does	0
not	0
affect	0
memory	0
function	0
.	0

Present	0
study	0
clearly	0
suggests	0
that	0
glial	0
activation	0
and	0
post	0
synaptic	0
neurotoxicity	3
are	0
the	0
key	0
factors	0
in	0
STZ	1
induced	0
memory	3
impairment	4
and	0
neuronal	0
cell	0
death	0
.	0

Comparison	0
of	0
effects	0
of	0
isotonic	0
sodium	1
chloride	2
with	0
diltiazem	1
in	0
prevention	0
of	0
contrast	1
-	0
induced	0
nephropathy	3
.	0

INTR0DUCTI0N	0
AND	0
0BJECTIVE	0
:	0
Contrast	1
-	0
induced	0
nephropathy	3
(	0
CIN	0
)	0
significantly	0
increases	0
the	0
morbidity	0
and	0
mortality	0
of	0
patients	0
.	0

The	0
aim	0
of	0
this	0
study	0
is	0
to	0
investigate	0
and	0
compare	0
the	0
protective	0
effects	0
of	0
isotonic	0
sodium	1
chloride	2
with	0
sodium	1
bicarbonate	2
infusion	0
and	0
isotonic	0
sodium	1
chloride	2
infusion	0
with	0
diltiazem	1
,	0
a	0
calcium	1
channel	0
blocker	0
,	0
in	0
preventing	0
CIN	0
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
0ur	0
study	0
included	0
patients	0
who	0
were	0
administered	0
30	0
-	0
60	0
mL	0
of	0
iodinated	0
contrast	1
agent	0
for	0
percutaneous	0
coronary	0
angiography	0
(	0
PCAG	0
)	0
,	0
all	0
with	0
creatinine	1
values	0
between	0
1	0
.	0
1	0
and	0
3	0
.	0
1	0
mg	0
/	0
dL	0
.	0

Patients	0
were	0
divided	0
into	0
three	0
groups	0
and	0
each	0
group	0
had	0
20	0
patients	0
.	0

The	0
first	0
group	0
of	0
patients	0
was	0
administered	0
isotonic	0
sodium	1
chloride	2
;	0
the	0
second	0
group	0
was	0
administered	0
a	0
solution	0
that	0
of	0
5	0
%	0
dextrose	1
and	0
sodium	1
bicarbonate	2
,	0
while	0
the	0
third	0
group	0
was	0
administered	0
isotonic	0
sodium	1
chloride	2
before	0
and	0
after	0
the	0
contrast	1
injection	0
.	0

The	0
third	0
group	0
received	0
an	0
additional	0
injection	0
of	0
diltiazem	1
the	0
day	0
before	0
and	0
first	0
2	0
days	0
after	0
the	0
contrast	1
injection	0
.	0

All	0
of	0
the	0
patients	0
'	0
plasma	0
blood	1
urea	2
nitrogen	2
(	0
BUN	1
)	0
and	0
creatinine	1
levels	0
were	0
measured	0
on	0
the	0
second	0
and	0
seventh	0
day	0
after	0
the	0
administration	0
of	0
intravenous	0
contrast	1
material	0
.	0

RESULTS	0
:	0
The	0
basal	0
creatinine	1
levels	0
were	0
similar	0
for	0
all	0
three	0
groups	0
(	0
p	0
>	0
0	0
.	0
05	0
)	0
.	0

Among	0
a	0
total	0
of	0
60	0
patients	0
included	0
in	0
the	0
study	0
,	0
16	0
patients	0
developed	0
acute	3
renal	4
failure	4
(	0
ARF	3
)	0
on	0
the	0
second	0
day	0
after	0
contrast	1
material	0
was	0
injected	0
(	0
26	0
.	0
6	0
%	0
)	0
.	0

The	0
number	0
of	0
patients	0
who	0
developed	0
ARF	3
on	0
the	0
second	0
day	0
after	0
the	0
injection	0
in	0
the	0
first	0
group	0
was	0
five	0
(	0
25	0
%	0
)	0
,	0
in	0
the	0
second	0
group	0
was	0
six	0
(	0
30	0
%	0
)	0
and	0
the	0
third	0
group	0
was	0
five	0
(	0
25	0
%	0
)	0
(	0
p	0
>	0
0	0
.	0
05	0
)	0
.	0

C0NCLUSI0N	0
:	0
There	0
was	0
no	0
significant	0
difference	0
between	0
isotonic	0
sodium	1
chloride	2
,	0
sodium	1
bicarbonate	2
and	0
isotonic	0
sodium	1
chloride	2
with	0
diltiazem	1
application	0
in	0
prevention	0
of	0
CIN	0
.	0

Neurocognitive	0
and	0
neuroradiologic	0
central	0
nervous	0
system	0
late	0
effects	0
in	0
children	0
treated	0
on	0
Pediatric	0
0ncology	0
Group	0
(	0
P0G	0
)	0
P9605	0
(	0
standard	0
risk	0
)	0
and	0
P9201	0
(	0
lesser	0
risk	0
)	0
acute	3
lymphoblastic	4
leukemia	4
protocols	0
(	0
ACCL0131	0
)	0
:	0
a	0
methotrexate	1
consequence	0
?	0

A	0
report	0
from	0
the	0
Children	0
'	0
s	0
0ncology	0
Group	0
.	0

Concerns	0
about	0
long	0
-	0
term	0
methotrexate	1
(	0
MTX	1
)	0
neurotoxicity	3
in	0
the	0
1990s	0
led	0
to	0
modifications	0
in	0
intrathecal	0
(	0
IT	0
)	0
therapy	0
,	0
leucovorin	0
rescue	0
,	0
and	0
frequency	0
of	0
systemic	0
MTX	1
administration	0
in	0
children	0
with	0
acute	3
lymphoblastic	4
leukemia	4
.	0

In	0
this	0
study	0
,	0
neurocognitive	0
outcomes	0
and	0
neuroradiologic	0
evidence	0
of	0
leukoencephalopathy	3
were	0
compared	0
in	0
children	0
treated	0
with	0
intense	0
central	0
nervous	0
system	0
(	0
CNS	0
)	0
-	0
directed	0
therapy	0
(	0
P9605	0
)	0
versus	0
those	0
receiving	0
fewer	0
CNS	0
-	0
directed	0
treatment	0
days	0
during	0
intensive	0
consolidation	0
(	0
P9201	0
)	0
.	0

A	0
total	0
of	0
66	0
children	0
from	0
16	0
Pediatric	0
0ncology	0
Group	0
institutions	0
with	0
"	0
standard	0
-	0
risk	0
"	0
acute	3
lymphoblastic	4
leukemia	4
,	0
1	0
.	0
00	0
to	0
9	0
.	0
99	0
years	0
at	0
diagnosis	0
,	0
without	0
evidence	0
of	0
CNS	0
leukemia	3
at	0
diagnosis	0
were	0
enrolled	0
on	0
ACCL0131	0
:	0
28	0
from	0
P9201	0
and	0
38	0
from	0
P9605	0
.	0

Magnetic	0
resonance	0
imaging	0
scans	0
and	0
standard	0
neuropsychological	0
tests	0
were	0
performed	0
>	0
2	0
.	0
6	0
years	0
after	0
the	0
end	0
of	0
treatment	0
.	0

Significantly	0
more	0
P9605	0
patients	0
developed	0
leukoencephalopathy	3
compared	0
with	0
P9201	0
patients	0
(	0
68	0
%	0
,	0
95	0
%	0
confidence	0
interval	0
49	0
%	0
-	0
83	0
%	0
vs	0
.	0
22	0
%	0
,	0
95	0
%	0
confidence	0
interval	0
5	0
%	0
-	0
44	0
%	0
;	0
P	0
=	0
0	0
.	0
001	0
)	0
identified	0
as	0
late	0
as	0
7	0
.	0
7	0
years	0
after	0
the	0
end	0
of	0
treatment	0
.	0

0verall	0
,	0
40	0
%	0
of	0
patients	0
scored	0
<	0
85	0
on	0
either	0
Verbal	0
or	0
Performance	0
IQ	0
.	0

Children	0
on	0
both	0
studies	0
had	0
significant	0
attention	3
problems	4
,	0
but	0
P9605	0
children	0
scored	0
below	0
average	0
on	0
more	0
neurocognitive	0
measures	0
than	0
those	0
treated	0
on	0
P9201	0
(	0
82	0
%	0
,	0
14	0
/	0
17	0
measures	0
vs	0
.	0
24	0
%	0
,	0
4	0
/	0
17	0
measures	0
)	0
.	0

This	0
supports	0
ongoing	0
concerns	0
about	0
intensive	0
MTX	1
exposure	0
as	0
a	0
major	0
contributor	0
to	0
CNS	0
late	0
effects	0
.	0

Tranexamic	1
acid	2
overdosage	0
-	0
induced	0
generalized	0
seizure	3
in	0
renal	3
failure	4
.	0

We	0
report	0
a	0
45	0
-	0
year	0
-	0
old	0
lady	0
with	0
chronic	3
kidney	4
disease	4
stage	0
4	0
due	0
to	0
chronic	0
tubulointerstial	3
disease	4
.	0

She	0
was	0
admitted	0
to	0
our	0
center	0
for	0
severe	0
anemia	3
due	0
to	0
menorrhagia	3
and	0
deterioration	3
of	4
renal	4
function	4
.	0

She	0
was	0
infused	0
three	0
units	0
of	0
packed	0
cells	0
during	0
a	0
session	0
of	0
hemodialysis	0
.	0

Tranexamic	1
acid	2
(	0
TNA	1
)	0
1	0
g	0
8	0
-	0
hourly	0
was	0
administered	0
to	0
her	0
to	0
control	0
bleeding	3
per	0
vaginum	0
.	0

Two	0
hours	0
after	0
the	0
sixth	0
dose	0
of	0
TNA	1
,	0
she	0
had	0
an	0
episode	0
of	0
generalized	0
tonic	3
clonic	4
convulsions	4
.	0

TNA	1
was	0
discontinued	0
.	0

Investigations	0
of	0
the	0
patient	0
revealed	0
no	0
biochemical	0
or	0
structural	0
central	0
nervous	3
system	4
abnormalities	4
that	0
could	0
have	0
provoked	0
the	0
convulsions	3
.	0

She	0
did	0
not	0
require	0
any	0
further	0
dialytic	0
support	0
.	0

She	0
had	0
no	0
further	0
episodes	0
of	0
convulsion	3
till	0
dis	0
-	0
charge	0
and	0
during	0
the	0
two	0
months	0
of	0
follow	0
-	0
up	0
.	0

Thus	0
,	0
the	0
precipitating	0
cause	0
of	0
convulsions	3
was	0
believed	0
to	0
be	0
an	0
overdose	3
of	0
TNA	1
.	0

Pre	0
-	0
treatment	0
of	0
bupivacaine	1
-	0
induced	0
cardiovascular	3
depression	4
using	0
different	0
lipid	0
formulations	0
of	0
propofol	1
.	0

BACKGR0UND	0
:	0
Pre	0
-	0
treatment	0
with	0
lipid	0
emulsions	0
has	0
been	0
shown	0
to	0
increase	0
lethal	0
doses	0
of	0
bupivacaine	1
,	0
and	0
the	0
lipid	0
content	0
of	0
propofol	1
may	0
alleviate	0
bupivacaine	1
-	0
induced	0
cardiotoxicity	3
.	0

The	0
aim	0
of	0
this	0
study	0
is	0
to	0
investigate	0
the	0
effects	0
of	0
propofol	1
in	0
intralipid	0
or	0
medialipid	0
emulsions	0
on	0
bupivacaine	1
-	0
induced	0
cardiotoxicity	3
.	0

METH0DS	0
:	0
Rats	0
were	0
anaesthetised	0
with	0
ketamine	1
and	0
were	0
given	0
0	0
.	0
5	0
mg	0
/	0
kg	0
/	0
min	0
propofol	1
in	0
intralipid	0
(	0
Group	0
P	0
)	0
,	0
propofol	1
in	0
medialipid	0
(	0
Group	0
L	0
)	0
,	0
or	0
saline	0
(	0
Group	0
C	0
)	0
over	0
20	0
min	0
.	0

Thereafter	0
,	0
2	0
mg	0
/	0
kg	0
/	0
min	0
bupivacaine	1
0	0
.	0
5	0
%	0
was	0
infused	0
.	0

We	0
recorded	0
time	0
to	0
first	0
dysrhythmia	3
occurrence	0
,	0
respective	0
times	0
to	0
25	0
%	0
and	0
50	0
%	0
reduction	0
of	0
the	0
heart	0
rate	0
(	0
HR	0
)	0
and	0
mean	0
arterial	0
pressure	0
,	0
and	0
time	0
to	0
asystole	3
and	0
total	0
amount	0
of	0
bupivacaine	1
consumption	0
.	0

Blood	0
and	0
tissue	0
samples	0
were	0
collected	0
following	0
asystole	3
.	0

RESULTS	0
:	0
The	0
time	0
to	0
first	0
dysrhythmia	3
occurrence	0
,	0
time	0
to	0
25	0
%	0
and	0
50	0
%	0
reductions	0
in	0
HR	0
,	0
and	0
time	0
to	0
asystole	3
were	0
longer	0
in	0
Group	0
P	0
than	0
the	0
other	0
groups	0
.	0

The	0
cumulative	0
bupivacaine	1
dose	0
given	0
at	0
those	0
time	0
points	0
was	0
higher	0
in	0
Group	0
P	0
.	0
Plasma	0
bupivacaine	1
levels	0
were	0
significantly	0
lower	0
in	0
Group	0
P	0
than	0
in	0
Group	0
C	0
.	0
Bupivacaine	1
levels	0
in	0
the	0
brain	0
and	0
heart	0
were	0
significantly	0
lower	0
in	0
Group	0
P	0
and	0
Group	0
L	0
than	0
in	0
Group	0
C	0
.	0

C0NCLUSI0N	0
:	0
We	0
conclude	0
that	0
pre	0
-	0
treatment	0
with	0
propofol	1
in	0
intralipid	0
,	0
compared	0
with	0
propofol	1
in	0
medialipid	0
or	0
saline	0
,	0
delayed	0
the	0
onset	0
of	0
bupivacaine	1
-	0
induced	0
cardiotoxic	3
effects	0
as	0
well	0
as	0
reduced	0
plasma	0
bupivacaine	1
levels	0
.	0

Further	0
studies	0
are	0
needed	0
to	0
explore	0
tissue	0
bupivacaine	1
levels	0
of	0
propofol	1
in	0
medialipid	0
and	0
adapt	0
these	0
results	0
to	0
clinical	0
practice	0
.	0

Drug	3
-	4
Induced	4
Acute	4
Liver	4
Injury	4
Within	0
12	0
Hours	0
After	0
Fluvastatin	1
Therapy	0
.	0

Although	0
statins	1
are	0
generally	0
well	0
-	0
tolerated	0
drugs	0
,	0
recent	0
cases	0
of	0
drug	3
-	4
induced	4
liver	4
injury	4
associated	0
with	0
their	0
use	0
have	0
been	0
reported	0
.	0

A	0
52	0
-	0
year	0
-	0
old	0
Chinese	0
man	0
reported	0
with	0
liver	3
damage	4
,	0
which	0
appeared	0
12	0
hours	0
after	0
beginning	0
treatment	0
with	0
fluvastatin	1
.	0

Patient	0
presented	0
with	0
complaints	0
of	0
increasing	0
nausea	3
,	0
anorexia	3
,	0
and	0
upper	0
abdominal	3
pain	4
.	0

His	0
laboratory	0
values	0
showed	0
elevated	0
creatine	1
kinase	0
and	0
transaminases	0
.	0

Testing	0
for	0
autoantibodies	0
was	0
also	0
negative	0
.	0

The	0
liver	0
biochemistries	0
eventually	0
normalized	0
within	0
3	0
weeks	0
of	0
stopping	0
the	0
fluvastatin	1
.	0

Therefore	0
,	0
when	0
prescribing	0
statins	0
,	0
the	0
possibility	0
of	0
hepatic	3
damage	4
should	0
be	0
taken	0
into	0
account	0
.	0

Fluconazole	1
associated	0
agranulocytosis	3
and	0
thrombocytopenia	3
.	0

CASE	0
:	0
We	0
describe	0
a	0
second	0
case	0
of	0
fluconazole	1
associated	0
agranulocytosis	3
with	0
thrombocytopenia	3
and	0
recovery	0
upon	0
discontinuation	0
of	0
therapy	0
.	0

The	0
patient	0
began	0
to	0
have	0
changes	0
in	0
white	0
blood	0
cells	0
and	0
platelets	0
within	0
48	0
h	0
of	0
administration	0
of	0
fluconazole	1
and	0
began	0
to	0
recover	0
with	0
48	0
h	0
of	0
discontinuation	0
.	0

This	0
case	0
highlights	0
that	0
drug	0
-	0
induced	0
blood	3
dyscrasias	4
can	0
occur	0
unexpectedly	0
as	0
a	0
result	0
of	0
treatment	0
with	0
a	0
commonly	0
used	0
drug	0
thought	0
to	0
be	0
"	0
safe	0
"	0
.	0

C0NCLUSI0N	0
:	0
According	0
to	0
Naranjo	0
'	0
s	0
algorithm	0
the	0
likelihood	0
that	0
our	0
patient	0
'	0
s	0
agranulocytosis	3
and	0
thrombocytopenia	3
occurred	0
as	0
a	0
result	0
of	0
therapy	0
with	0
fluconazole	1
is	0
probable	0
,	0
with	0
a	0
total	0
of	0
six	0
points	0
.	0

We	0
feel	0
that	0
the	0
weight	0
of	0
the	0
overall	0
evidence	0
of	0
this	0
evidence	0
is	0
strong	0
.	0

In	0
particular	0
the	0
temporal	0
relationship	0
of	0
bone	3
marrow	4
suppression	4
to	0
the	0
initiation	0
of	0
fluconazole	1
and	0
the	0
abatement	0
of	0
symptoms	0
that	0
rapidly	0
reversed	0
immediately	0
following	0
discontinuation	0
.	0

Two	0
-	0
dimensional	0
speckle	0
tracking	0
echocardiography	0
combined	0
with	0
high	0
-	0
sensitive	0
cardiac	0
troponin	0
T	0
in	0
early	0
detection	0
and	0
prediction	0
of	0
cardiotoxicity	3
during	0
epirubicine	1
-	0
based	0
chemotherapy	0
.	0

AIMS	0
:	0
To	0
investigate	0
whether	0
alterations	0
of	0
myocardial	3
strain	4
and	0
high	0
-	0
sensitive	0
cardiac	0
troponin	0
T	0
(	0
cTnT	0
)	0
could	0
predict	0
future	0
cardiac	3
dysfunction	4
in	0
patients	0
after	0
epirubicin	1
exposure	0
.	0

METH0DS	0
:	0
Seventy	0
-	0
five	0
patients	0
with	0
non	3
-	4
Hodgkin	4
lymphoma	4
treated	0
with	0
epirubicin	1
were	0
studied	0
.	0

Blood	0
collection	0
and	0
echocardiography	0
were	0
performed	0
at	0
baseline	0
,	0
1	0
day	0
after	0
the	0
third	0
cycle	0
,	0
and	0
1	0
day	0
after	0
completion	0
of	0
chemotherapy	0
.	0

Patients	0
were	0
studied	0
using	0
echocardiography	0
during	0
follow	0
-	0
up	0
.	0

Global	0
longitudinal	0
(	0
GLS	0
)	0
,	0
circumferential	0
(	0
GCS	0
)	0
,	0
and	0
radial	0
strain	0
(	0
GRS	0
)	0
were	0
calculated	0
using	0
speckle	0
tracking	0
echocardiography	0
.	0

Left	0
ventricular	0
ejection	0
fraction	0
was	0
analysed	0
by	0
real	0
-	0
time	0
3D	0
echocardiography	0
.	0

Cardiotoxicity	3
was	0
defined	0
as	0
a	0
reduction	0
of	0
the	0
LVEF	0
of	0
>	0
5	0
%	0
to	0
<	0
55	0
%	0
with	0
symptoms	0
of	0
heart	3
failure	4
or	0
an	0
asymptomatic	0
reduction	0
of	0
the	0
LVEF	0
of	0
>	0
10	0
%	0
to	0
<	0
55	0
%	0
.	0

RESULTS	0
:	0
Fourteen	0
patients	0
(	0
18	0
.	0
67	0
%	0
)	0
developed	0
cardiotoxicity	3
after	0
treatment	0
.	0

GLS	0
(	0
-	0
18	0
.	0
48	0
+	0
1	0
.	0
72	0
%	0
vs	0
.	0
-	0
15	0
.	0
96	0
+	0
1	0
.	0
6	0
%	0
)	0
,	0
GCS	0
(	0
-	0
20	0
.	0
93	0
+	0
2	0
.	0
86	0
%	0
vs	0
.	0
-	0
19	0
.	0
20	0
+	0
3	0
.	0
21	0
%	0
)	0
,	0
and	0
GRS	0
(	0
39	0
.	0
23	0
+	0
6	0
.	0
44	0
%	0
vs	0
.	0
34	0
.	0
98	0
+	0
6	0
.	0
2	0
%	0
)	0
were	0
markedly	0
reduced	0
and	0
cTnT	0
was	0
elevated	0
from	0
0	0
.	0
0010	0
+	0
0	0
.	0
0020	0
to	0
0	0
.	0
0073	0
+	0
0	0
.	0
0038	0
ng	0
/	0
mL	0
(	0
P	0
all	0
<	0
0	0
.	0
01	0
)	0
at	0
the	0
completion	0
of	0
chemotherapy	0
compared	0
with	0
baseline	0
values	0
.	0

A	0
>	0
15	0
.	0
9	0
%	0
decrease	0
in	0
GLS	0
[	0
sensitivity	0
,	0
86	0
%	0
;	0
specificity	0
,	0
75	0
%	0
;	0
area	0
under	0
the	0
curve	0
(	0
AUC	0
)	0
=	0
0	0
.	0
815	0
;	0
P	0
=	0
0	0
.	0
001	0
]	0
and	0
a	0
>	0
0	0
.	0
004	0
ng	0
/	0
mL	0
elevation	0
in	0
cTnT	0
(	0
sensitivity	0
,	0
79	0
%	0
;	0
specificity	0
,	0
64	0
%	0
;	0
AUC	0
=	0
0	0
.	0
757	0
;	0
P	0
=	0
0	0
.	0
005	0
)	0
from	0
baseline	0
to	0
the	0
third	0
cycle	0
of	0
chemotherapy	0
predicted	0
later	0
cardiotoxicity	3
.	0

The	0
decrease	0
in	0
GLS	0
remained	0
the	0
only	0
independent	0
predictor	0
of	0
cardiotoxicity	3
(	0
P	0
=	0
0	0
.	0
000	0
)	0
.	0

C0NCLUSI0NS	0
:	0
GLS	0
combined	0
with	0
cTnT	0
may	0
provide	0
a	0
reliable	0
and	0
non	0
-	0
invasive	0
method	0
to	0
predict	0
cardiac	3
dysfunction	4
in	0
patients	0
receiving	0
anthracycline	1
-	0
based	0
chemotherapy	0
.	0

Prevention	0
of	0
etomidate	1
-	0
induced	0
myoclonus	3
:	0
which	0
is	0
superior	0
:	0
Fentanyl	1
,	0
midazolam	1
,	0
or	0
a	0
combination	0
?	0

A	0
Retrospective	0
comparative	0
study	0
.	0

BACKGR0UND	0
:	0
In	0
this	0
retrospective	0
comparative	0
study	0
,	0
we	0
aimed	0
to	0
compare	0
the	0
effectiveness	0
of	0
fentanyl	1
,	0
midazolam	1
,	0
and	0
a	0
combination	0
of	0
fentanyl	1
and	0
midazolam	1
to	0
prevent	0
etomidate	1
-	0
induced	0
myoclonus	3
.	0

MATERIAL	0
AND	0
METH0DS	0
:	0
This	0
study	0
was	0
performed	0
based	0
on	0
anesthesia	0
records	0
.	0

Depending	0
on	0
the	0
drugs	0
that	0
would	0
be	0
given	0
before	0
the	0
induction	0
of	0
anesthesia	0
with	0
etomidate	1
,	0
the	0
patients	0
were	0
separated	0
into	0
4	0
groups	0
:	0
no	0
pretreatment	0
(	0
Group	0
NP	0
)	0
,	0
fentanyl	1
1	0
ug	0
.	0
kg	0
-	0
1	0
(	0
Group	0
F	0
)	0
,	0
midazolam	1
0	0
.	0
03	0
mg	0
.	0
kg	0
-	0
1	0
(	0
Group	0
M	0
)	0
,	0
and	0
midazolam	1
0	0
.	0
015	0
mg	0
.	0
kg	0
-	0
1	0
+	0
fentanyl	1
0	0
.	0
5	0
ug	0
.	0
kg	0
-	0
1	0
(	0
Group	0
FM	0
)	0
.	0

Patients	0
who	0
received	0
the	0
same	0
anesthetic	0
procedure	0
were	0
selected	0
:	0
2	0
minutes	0
after	0
intravenous	0
injections	0
of	0
the	0
pretreatment	0
drugs	0
,	0
anesthesia	0
is	0
induced	0
with	0
0	0
.	0
3	0
mg	0
.	0
kg	0
-	0
1	0
etomidate	1
injected	0
intravenously	0
over	0
a	0
period	0
of	0
20	0
-	0
30	0
seconds	0
.	0

Myoclonic	3
movements	4
are	0
evaluated	0
,	0
which	0
were	0
observed	0
and	0
graded	0
according	0
to	0
clinical	0
severity	0
during	0
the	0
2	0
minutes	0
after	0
etomidate	1
injection	0
.	0

The	0
severity	0
of	0
pain	3
due	0
to	0
etomidate	1
injection	0
,	0
mean	0
arterial	0
pressure	0
,	0
heart	0
rate	0
,	0
and	0
adverse	0
effects	0
were	0
also	0
evaluated	0
.	0

RESULTS	0
:	0
Study	0
results	0
showed	0
that	0
myoclonus	3
incidence	0
was	0
85	0
%	0
,	0
40	0
%	0
,	0
70	0
%	0
,	0
and	0
25	0
%	0
in	0
Group	0
NP	0
,	0
Group	0
F	0
,	0
Group	0
M	0
,	0
and	0
Group	0
FM	0
,	0
respectively	0
,	0
and	0
were	0
significantly	0
lower	0
in	0
Group	0
F	0
and	0
Group	0
FM	0
.	0

C0NCLUSI0NS	0
:	0
We	0
conclude	0
that	0
pretreatment	0
with	0
fentanyl	1
or	0
combination	0
of	0
fentanyl	1
and	0
midazolam	1
was	0
effective	0
in	0
preventing	0
etomidate	1
-	0
induced	0
myoclonus	3
.	0

Convulsant	0
effect	0
of	0
lindane	1
and	0
regional	0
brain	0
concentration	0
of	0
GABA	1
and	0
dopamine	1
.	0

Lindane	1
(	0
gamma	1
-	2
hexachlorocyclohexane	2
)	0
is	0
an	0
organochlorine	0
insecticide	0
with	0
known	0
neurotoxic	3
effects	0
.	0

Its	0
mechanism	0
of	0
action	0
is	0
not	0
well	0
understood	0
although	0
it	0
has	0
been	0
proposed	0
that	0
lindane	1
acts	0
as	0
a	0
non	0
-	0
competitive	0
antagonist	0
at	0
the	0
gamma	1
-	2
aminobutyric	2
acid	2
(	0
GABA	1
)	0
-	0
A	0
receptor	0
.	0

We	0
studied	0
the	0
effect	0
of	0
lindane	1
(	0
150	0
mg	0
/	0
kg	0
)	0
on	0
the	0
GABAergic	0
and	0
dopaminergic	0
systems	0
by	0
measuring	0
the	0
concentration	0
of	0
GABA	1
,	0
dopamine	1
and	0
its	0
metabolites	0
in	0
7	0
brain	0
areas	0
at	0
the	0
onset	0
of	0
seizures	3
.	0

All	0
animals	0
suffered	0
tonic	0
convulsions	3
at	0
18	0
.	0
3	0
+	0
/	0
-	0
1	0
.	0
4	0
min	0
after	0
lindane	1
administration	0
.	0

The	0
concentration	0
of	0
GABA	1
was	0
only	0
slightly	0
but	0
significantly	0
decreased	0
in	0
the	0
colliculi	0
without	0
modifications	0
in	0
the	0
other	0
areas	0
.	0

The	0
concentration	0
of	0
dopamine	1
was	0
increased	0
in	0
the	0
mesencephalon	0
and	0
that	0
of	0
its	0
metabolite	0
D0PAC	1
was	0
also	0
increased	0
in	0
the	0
mesencephalon	0
and	0
the	0
striatum	0
.	0

Cholestatic	3
presentation	0
of	0
yellow	0
phosphorus	1
poisoning	3
.	0

Yellow	0
phosphorus	1
,	0
a	0
component	0
of	0
certain	0
pesticide	0
pastes	0
and	0
fireworks	0
,	0
is	0
well	0
known	0
to	0
cause	0
hepatotoxicity	3
.	0

Poisoning	3
with	0
yellow	0
phosphorus	1
classically	0
manifests	0
with	0
acute	3
hepatitis	4
leading	0
to	0
acute	3
liver	4
failure	4
which	0
may	0
need	0
liver	0
transplantation	0
.	0

We	0
present	0
a	0
case	0
of	0
yellow	0
phosphorus	1
poisoning	3
in	0
which	0
a	0
patient	0
presented	0
with	0
florid	0
clinical	0
features	0
of	0
cholestasis	3
highlighting	0
the	0
fact	0
that	0
cholestasis	3
can	0
rarely	0
be	0
a	0
presenting	0
feature	0
of	0
yellow	0
phosphorus	1
hepatotoxicity	3
.	0

Vasovagal	3
syncope	4
and	0
severe	0
bradycardia	3
following	0
intranasal	0
dexmedetomidine	1
for	0
pediatric	0
procedural	0
sedation	0
.	0

We	0
report	0
syncope	3
and	0
bradycardia	3
in	0
an	0
11	0
-	0
year	0
-	0
old	0
girl	0
following	0
administration	0
of	0
intranasal	0
dexmedetomidine	1
for	0
sedation	0
for	0
a	0
voiding	0
cystourethrogram	0
.	0

Following	0
successful	0
completion	0
of	0
VCUG	0
and	0
a	0
60	0
-	0
min	0
recovery	0
period	0
,	0
the	0
patient	0
'	0
s	0
level	0
of	0
consciousness	0
and	0
vital	0
signs	0
returned	0
to	0
presedation	0
levels	0
.	0

Upon	0
leaving	0
the	0
sedation	0
area	0
,	0
the	0
patient	0
collapsed	0
,	0
with	0
no	0
apparent	0
inciting	0
event	0
.	0

The	0
patient	0
quickly	0
regained	0
consciousness	0
and	0
no	0
injury	0
occurred	0
.	0

The	0
primary	0
abnormality	0
found	0
was	0
persistent	0
bradycardia	3
,	0
and	0
she	0
was	0
admitted	0
to	0
the	0
hospital	0
for	0
telemetric	0
observation	0
.	0

The	0
bradycardia	3
lasted	0
~	0
2	0
h	0
,	0
and	0
further	0
cardiac	0
workup	0
revealed	0
no	0
underlying	0
abnormality	0
.	0

Unanticipated	0
and	0
previously	0
unreported	0
outcomes	0
may	0
be	0
witnessed	0
as	0
we	0
expand	0
the	0
use	0
of	0
certain	0
sedatives	0
to	0
alternative	0
routes	0
of	0
administration	0
.	0

Paradoxical	0
severe	0
agitation	3
induced	0
by	0
add	0
-	0
on	0
high	0
-	0
doses	0
quetiapine	1
in	0
schizo	3
-	4
affective	4
disorder	4
.	0

We	0
report	0
the	0
case	0
of	0
a	0
35	0
-	0
year	0
-	0
old	0
patient	0
suffering	0
from	0
schizo	3
-	4
affective	4
disorder	4
since	0
the	0
age	0
of	0
19	0
years	0
,	0
treated	0
by	0
a	0
combination	0
of	0
first	0
-	0
generation	0
antipsychotics	0
,	0
zuclopenthixol	1
(	0
100	0
mg	0
/	0
day	0
)	0
and	0
lithium	1
(	0
1200	0
mg	0
/	0
day	0
)	0
(	0
serum	0
lithium	1
=	0
0	0
.	0
85	0
mEq	0
/	0
l	0
)	0
.	0

This	0
patient	0
had	0
no	0
associated	0
personality	3
disorder	4
(	0
particularly	0
no	0
antisocial	3
disorder	4
)	0
and	0
no	0
substance	3
abuse	4
disorder	4
.	0

Within	0
the	0
48	0
h	0
following	0
the	0
gradual	0
introduction	0
of	0
quetiapine	1
(	0
up	0
to	0
600	0
mg	0
/	0
day	0
)	0
,	0
the	0
patient	0
presented	0
severe	0
agitation	3
without	0
an	0
environmental	0
explanation	0
,	0
contrasting	0
with	0
the	0
absence	0
of	0
a	0
history	0
of	0
aggressiveness	3
or	0
personality	3
disorder	4
.	0

The	0
diagnoses	0
of	0
manic	3
shift	0
and	0
akathisia	3
were	0
dismissed	0
.	0

The	0
withdrawal	0
and	0
the	0
gradual	0
reintroduction	0
of	0
quetiapine	1
2	0
weeks	0
later	0
,	0
which	0
led	0
to	0
another	0
severe	0
agitation	3
,	0
enabled	0
us	0
to	0
attribute	0
the	0
agitation	3
specifically	0
to	0
quetiapine	1
.	0

Antioxidant	0
effects	0
of	0
bovine	0
lactoferrin	0
on	0
dexamethasone	1
-	0
induced	0
hypertension	3
in	0
rat	0
.	0

Dexamethasone	1
-	0
(	0
Dex	1
-	0
)	0
induced	0
hypertension	3
is	0
associated	0
with	0
enhanced	0
oxidative	0
stress	0
.	0

Lactoferrin	0
(	0
LF	0
)	0
is	0
an	0
iron	1
-	0
binding	0
glycoprotein	0
with	0
antihypertensive	0
properties	0
.	0

In	0
this	0
study	0
,	0
we	0
investigated	0
the	0
effect	0
of	0
chronic	0
administration	0
of	0
LF	0
on	0
oxidative	0
stress	0
and	0
hypertension	3
upon	0
Dex	1
administration	0
.	0

Male	0
Wistar	0
rats	0
were	0
treated	0
by	0
Dex	1
(	0
30	0
u	0
g	0
/	0
kg	0
/	0
day	0
subcutaneously	0
)	0
or	0
saline	0
for	0
14	0
days	0
.	0

0ral	0
bovine	0
LF	0
(	0
30	0
,	0
100	0
,	0
300	0
mg	0
/	0
kg	0
)	0
was	0
given	0
from	0
day	0
8	0
to	0
14	0
in	0
a	0
reversal	0
study	0
.	0

In	0
a	0
prevention	0
study	0
,	0
rats	0
received	0
4	0
days	0
of	0
LF	0
treatment	0
followed	0
by	0
Dex	1
and	0
continued	0
during	0
the	0
test	0
period	0
.	0

Systolic	0
blood	0
pressure	0
(	0
SBP	0
)	0
was	0
measured	0
using	0
tail	0
-	0
cuff	0
method	0
.	0

Thymus	0
weight	0
was	0
used	0
as	0
a	0
marker	0
of	0
glucocorticoid	0
activity	0
.	0

Plasma	0
hydrogen	1
peroxide	2
(	0
H202	1
)	0
concentration	0
and	0
ferric	0
reducing	0
antioxidant	0
power	0
(	0
FRAP	0
)	0
value	0
were	0
determined	0
.	0

Dexamethasone	1
significantly	0
increased	0
SBP	0
and	0
plasma	0
H202	1
level	0
and	0
decreased	0
thymus	0
and	0
body	0
weights	0
.	0

LF	0
lowered	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
and	0
dose	0
dependently	0
prevented	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
Dex	1
-	0
induced	0
hypertension	3
.	0

LF	0
prevented	0
body	0
weight	3
loss	4
and	0
significantly	0
reduced	0
the	0
elevated	0
plasma	0
H202	1
and	0
increased	0
FRAP	0
values	0
.	0

Chronic	0
administration	0
of	0
LF	0
strongly	0
reduced	0
the	0
blood	0
pressure	0
and	0
production	0
of	0
R0S	0
and	0
improved	0
antioxidant	0
capacity	0
in	0
Dex	1
-	0
induced	0
hypertension	3
,	0
suggesting	0
the	0
role	0
of	0
inhibition	0
of	0
oxidative	0
stress	0
as	0
another	0
mechanism	0
of	0
antihypertensive	0
action	0
of	0
LF	0
.	0

The	0
association	0
between	0
tranexamic	1
acid	2
and	0
convulsive	3
seizures	3
after	0
cardiac	0
surgery	0
:	0
a	0
multivariate	0
analysis	0
in	0
11	0
529	0
patients	0
.	0

Because	0
of	0
a	0
lack	0
of	0
contemporary	0
data	0
regarding	0
seizures	3
after	0
cardiac	0
surgery	0
,	0
we	0
undertook	0
a	0
retrospective	0
analysis	0
of	0
prospectively	0
collected	0
data	0
from	0
11	0
529	0
patients	0
in	0
whom	0
cardiopulmonary	0
bypass	0
was	0
used	0
from	0
January	0
2004	0
to	0
December	0
2010	0
.	0

A	0
convulsive	3
seizure	3
was	0
defined	0
as	0
a	0
transient	0
episode	0
of	0
disturbed	0
brain	0
function	0
characterised	0
by	0
abnormal	3
involuntary	4
motor	4
movements	4
.	0

Multivariate	0
regression	0
analysis	0
was	0
performed	0
to	0
identify	0
independent	0
predictors	0
of	0
postoperative	0
seizures	3
.	0

A	0
total	0
of	0
100	0
(	0
0	0
.	0
9	0
%	0
)	0
patients	0
developed	0
postoperative	0
convulsive	3
seizures	3
.	0

Generalised	3
and	4
focal	4
seizures	4
were	0
identified	0
in	0
68	0
and	0
32	0
patients	0
,	0
respectively	0
.	0

The	0
median	0
(	0
IQR	0
[	0
range	0
]	0
)	0
time	0
after	0
surgery	0
when	0
the	0
seizure	3
occurred	0
was	0
7	0
(	0
6	0
-	0
12	0
[	0
1	0
-	0
216	0
]	0
)	0
h	0
and	0
8	0
(	0
6	0
-	0
11	0
[	0
4	0
-	0
18	0
]	0
)	0
h	0
,	0
respectively	0
.	0

Epileptiform	0
findings	0
on	0
electroencephalography	0
were	0
seen	0
in	0
19	0
patients	0
.	0

Independent	0
predictors	0
of	0
postoperative	0
seizures	3
included	0
age	0
,	0
female	0
sex	0
,	0
redo	0
cardiac	0
surgery	0
,	0
calcification	0
of	0
ascending	0
aorta	0
,	0
congestive	3
heart	4
failure	4
,	0
deep	0
hypothermic	3
circulatory	0
arrest	0
,	0
duration	0
of	0
aortic	0
cross	0
-	0
clamp	0
and	0
tranexamic	1
acid	2
.	0

When	0
tested	0
in	0
a	0
multivariate	0
regression	0
analysis	0
,	0
tranexamic	1
acid	2
was	0
a	0
strong	0
independent	0
predictor	0
of	0
seizures	3
(	0
0R	0
14	0
.	0
3	0
,	0
95	0
%	0
CI	0
5	0
.	0
5	0
-	0
36	0
.	0
7	0
;	0
p	0
<	0
0	0
.	0
001	0
)	0
.	0

Patients	0
with	0
convulsive	3
seizures	3
had	0
2	0
.	0
5	0
times	0
higher	0
in	0
-	0
hospital	0
mortality	0
rates	0
and	0
twice	0
the	0
length	0
of	0
hospital	0
stay	0
compared	0
with	0
patients	0
without	0
convulsive	3
seizures	3
.	0

Mean	0
(	0
IQR	0
[	0
range	0
]	0
)	0
length	0
of	0
stay	0
in	0
the	0
intensive	0
care	0
unit	0
was	0
115	0
(	0
49	0
-	0
228	0
[	0
32	0
-	0
481	0
]	0
)	0
h	0
in	0
patients	0
with	0
convulsive	3
seizures	3
compared	0
with	0
26	0
(	0
22	0
-	0
69	0
[	0
14	0
-	0
1080	0
]	0
)	0
h	0
in	0
patients	0
without	0
seizures	3
(	0
p	0
<	0
0	0
.	0
001	0
)	0
.	0

Convulsive	3
seizures	3
are	0
a	0
serious	0
postoperative	3
complication	4
after	0
cardiac	0
surgery	0
.	0

As	0
tranexamic	1
acid	2
is	0
the	0
only	0
modifiable	0
factor	0
,	0
its	0
administration	0
,	0
particularly	0
in	0
doses	0
exceeding	0
80	0
mg	0
.	0
kg	0
(	0
-	0
1	0
)	0
,	0
should	0
be	0
weighed	0
against	0
the	0
risk	0
of	0
postoperative	0
seizures	3
.	0

Dysfunctional	3
overnight	4
memory	4
consolidation	0
in	0
ecstasy	1
users	0
.	0

Sleep	0
plays	0
an	0
important	0
role	0
in	0
the	0
consolidation	0
and	0
integration	0
of	0
memory	0
in	0
a	0
process	0
called	0
overnight	0
memory	0
consolidation	0
.	0

Previous	0
studies	0
indicate	0
that	0
ecstasy	1
users	0
have	0
marked	0
and	0
persistent	0
neurocognitive	0
and	0
sleep	3
-	4
related	4
impairments	4
.	0

We	0
extend	0
past	0
research	0
by	0
examining	0
overnight	0
memory	0
consolidation	0
among	0
regular	0
ecstasy	1
users	0
(	0
n	0
=	0
12	0
)	0
and	0
drug	0
naive	0
healthy	0
controls	0
(	0
n	0
=	0
26	0
)	0
.	0

Memory	0
recall	0
of	0
word	0
pairs	0
was	0
evaluated	0
before	0
and	0
after	0
a	0
period	0
of	0
sleep	0
,	0
with	0
and	0
without	0
interference	0
prior	0
to	0
testing	0
.	0

In	0
addition	0
,	0
we	0
assessed	0
neurocognitive	0
performances	0
across	0
tasks	0
of	0
learning	0
,	0
memory	0
and	0
executive	0
functioning	0
.	0

Ecstasy	1
users	0
demonstrated	0
impaired	3
overnight	4
memory	4
consolidation	0
,	0
a	0
finding	0
that	0
was	0
more	0
pronounced	0
following	0
associative	0
interference	0
.	0

Additionally	0
,	0
ecstasy	1
users	0
demonstrated	0
impairments	0
on	0
tasks	0
recruiting	0
frontostriatal	0
and	0
hippocampal	0
neural	0
circuitry	0
,	0
in	0
the	0
domains	0
of	0
proactive	0
interference	0
memory	0
,	0
long	0
-	0
term	0
memory	0
,	0
encoding	0
,	0
working	0
memory	0
and	0
complex	0
planning	0
.	0

We	0
suggest	0
that	0
ecstasy	1
-	0
associated	0
dysfunction	0
in	0
fronto	0
-	0
temporal	0
circuitry	0
may	0
underlie	0
overnight	0
consolidation	0
memory	3
impairments	4
in	0
regular	0
ecstasy	1
users	0
.	0

Normoammonemic	0
encephalopathy	3
:	0
solely	0
valproate	1
induced	0
or	0
multiple	0
mechanisms	0
?	0

A	0
77	0
-	0
year	0
-	0
old	0
woman	0
presented	0
with	0
subacute	0
onset	0
progressive	0
confusion	3
,	0
aggression	3
,	0
auditory	3
hallucinations	4
and	0
delusions	3
.	0

In	0
the	0
preceding	0
months	0
,	0
the	0
patient	0
had	0
a	0
number	0
of	0
admissions	0
with	0
transient	0
unilateral	0
hemiparesis	3
with	0
facial	0
droop	0
,	0
and	0
had	0
been	0
started	0
on	0
valproate	1
for	0
presumed	0
hemiplegic	3
migraine	4
.	0

Valproate	1
was	0
withdrawn	0
soon	0
after	0
admission	0
and	0
her	0
cognitive	0
abilities	0
have	0
gradually	0
improved	0
over	0
3	0
months	0
of	0
follow	0
-	0
up	0
.	0

Valproate	1
levels	0
taken	0
prior	0
to	0
withdrawal	0
were	0
subtherapeutic	0
and	0
the	0
patient	0
was	0
normoammonaemic	0
.	0

EEG	0
undertaken	0
during	0
inpatient	0
stay	0
showed	0
changes	0
consistent	0
with	0
encephalopathy	3
,	0
and	0
low	0
titre	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
(	0
NMDA	1
)	0
receptor	0
antibodies	0
were	0
present	0
in	0
this	0
patient	0
.	0

The	0
possible	0
aetiologies	0
of	0
valproate	1
-	0
induced	0
encephalopathy	3
and	0
NMDA	1
receptor	0
-	0
associated	0
encephalitis	3
present	0
a	0
diagnostic	0
dilemma	0
.	0

We	0
present	0
a	0
putative	0
combinatorial	0
hypothesis	0
to	0
explain	0
this	0
patient	0
'	0
s	0
symptoms	0
.	0

Cerebellar	3
and	4
oculomotor	4
dysfunction	4
induced	0
by	0
rapid	0
infusion	0
of	0
pethidine	1
.	0

Pethidine	1
is	0
an	0
opioid	0
that	0
gains	0
its	0
popularity	0
for	0
the	0
effective	0
pain	3
control	0
through	0
acting	0
on	0
the	0
opioid	0
-	0
receptors	0
.	0

However	0
,	0
rapid	0
pain	3
relief	0
sometimes	0
brings	0
about	0
unfavourable	0
side	0
effects	0
that	0
largely	0
limit	0
its	0
clinical	0
utility	0
.	0

Common	0
side	0
effects	0
include	0
nausea	3
,	0
vomiting	3
and	0
hypotension	3
.	0

In	0
patients	0
with	0
impaired	3
renal	4
and	4
liver	4
function	4
,	0
and	0
those	0
who	0
need	0
long	0
-	0
term	0
pain	3
control	0
,	0
pethidine	1
may	0
cause	0
excitatory	0
central	0
nervous	0
system	0
(	0
CNS	0
)	0
effects	0
through	0
its	0
neurotoxic	3
metabolite	0
,	0
norpethidine	1
,	0
resulting	0
in	0
irritability	3
and	0
seizure	3
attack	0
.	0

0n	0
the	0
contrary	0
,	0
though	0
not	0
clinically	0
apparent	0
,	0
pethidine	1
potentially	0
causes	0
inhibitory	0
impacts	0
on	0
the	0
CNS	0
and	0
impairs	0
normal	0
cerebellar	0
and	0
oculomotor	0
function	0
in	0
the	0
short	0
term	0
.	0

In	0
this	0
case	0
report	0
,	0
we	0
highlight	0
opioid	0
'	0
s	0
inhibitory	0
side	0
effects	0
on	0
the	0
cerebellar	0
structure	0
that	0
causes	0
dysmetria	3
,	0
dysarthria	3
,	0
reduced	0
smooth	0
pursuit	0
gain	0
and	0
decreased	0
saccadic	0
velocity	0
.	0

Baboon	3
syndrome	4
induced	0
by	0
ketoconazole	1
.	0

A	0
27	0
-	0
year	0
-	0
old	0
male	0
patient	0
presented	0
with	0
a	0
maculopapular	3
eruption	4
on	0
the	0
flexural	0
areas	0
and	0
buttocks	0
after	0
using	0
oral	0
ketoconazole	1
.	0

The	0
patient	0
was	0
diagnosed	0
with	0
drug	0
-	0
induced	0
baboon	3
syndrome	4
based	0
on	0
his	0
history	0
,	0
which	0
included	0
prior	0
sensitivity	0
to	0
topical	0
ketoconazole	1
,	0
a	0
physical	0
examination	0
,	0
and	0
histopathological	0
findings	0
.	0

Baboon	3
syndrome	4
is	0
a	0
drug	0
-	0
or	0
contact	0
allergen	0
-	0
related	0
maculopapular	3
eruption	4
that	0
typically	0
involves	0
the	0
flexural	0
and	0
gluteal	0
areas	0
.	0

To	0
the	0
best	0
of	0
our	0
knowledge	0
,	0
this	0
is	0
the	0
first	0
reported	0
case	0
of	0
ketoconazole	1
-	0
induced	0
baboon	3
syndrome	4
in	0
the	0
English	0
literature	0
.	0

A	0
Case	0
of	0
Sudden	3
Cardiac	4
Death	4
due	0
to	0
Pilsicainide	1
-	0
Induced	0
Torsades	3
de	4
Pointes	4
.	0

An	0
84	0
-	0
year	0
-	0
old	0
male	0
received	0
oral	0
pilsicainide	1
,	0
a	0
pure	0
sodium	1
channel	0
blocker	0
with	0
slow	0
recovery	0
kinetics	0
,	0
to	0
convert	0
his	0
paroxysmal	0
atrial	3
fibrillation	4
to	0
a	0
sinus	0
rhythm	0
;	0
the	0
patient	0
developed	0
sudden	3
cardiac	4
death	4
two	0
days	0
later	0
.	0

The	0
Holter	0
electrocardiogram	0
,	0
which	0
was	0
worn	0
by	0
chance	0
,	0
revealed	0
torsade	3
de	4
pointes	4
with	0
gradually	0
prolonged	0
QT	0
intervals	0
.	0

This	0
drug	0
is	0
rapidly	0
absorbed	0
from	0
the	0
gastrointestinal	0
tract	0
,	0
and	0
most	0
of	0
it	0
is	0
excreted	0
from	0
the	0
kidney	0
.	0

Although	0
the	0
patient	0
'	0
s	0
renal	0
function	0
was	0
not	0
highly	0
impaired	0
and	0
the	0
dose	0
of	0
pilsicainide	1
was	0
low	0
,	0
the	0
plasma	0
concentration	0
of	0
pilsicainide	1
may	0
have	0
been	0
high	0
,	0
which	0
can	0
produce	0
torsades	3
de	4
pointes	4
in	0
the	0
octogenarian	0
.	0

Although	0
the	0
oral	0
administration	0
of	0
class	0
IC	0
drugs	0
,	0
including	0
pilsicainide	1
,	0
is	0
effective	0
to	0
terminate	0
atrial	3
fibrillation	4
,	0
careful	0
consideration	0
must	0
be	0
taken	0
before	0
giving	0
these	0
drugs	0
to	0
octogenarians	0
.	0

All	1
-	2
trans	2
retinoic	2
acid	2
-	0
induced	0
inflammatory	0
myositis	3
in	0
a	0
patient	0
with	0
acute	3
promyelocytic	4
leukemia	4
.	0

All	1
-	2
trans	2
retinoic	2
acid	2
(	0
ATRA	1
)	0
,	0
a	0
component	0
of	0
standard	0
therapy	0
for	0
acute	3
promyelocytic	4
leukemia	4
(	0
APL	3
)	0
,	0
is	0
associated	0
with	0
potentially	0
serious	0
but	0
treatable	0
adverse	0
effects	0
involving	0
numerous	0
organ	0
systems	0
,	0
including	0
rare	0
skeletal	0
muscle	0
involvement	0
.	0

0nly	0
a	0
handful	0
of	0
cases	0
of	0
ATRA	1
-	0
induced	0
myositis	3
in	0
children	0
have	0
been	0
reported	0
,	0
and	0
none	0
in	0
the	0
radiology	0
literature	0
.	0

We	0
present	0
such	0
a	0
case	0
in	0
a	0
15	0
-	0
year	0
-	0
old	0
boy	0
with	0
APL	3
,	0
where	0
recognition	0
of	0
imaging	0
findings	0
played	0
a	0
crucial	0
role	0
in	0
making	0
the	0
diagnosis	0
and	0
facilitated	0
prompt	0
,	0
effective	0
treatment	0
.	0

Tolerability	0
of	0
lomustine	1
in	0
combination	0
with	0
cyclophosphamide	1
in	0
dogs	0
with	0
lymphoma	3
.	0

This	0
retrospective	0
study	0
describes	0
toxicity	3
associated	0
with	0
a	0
protocol	0
of	0
lomustine	1
(	0
CCNU	1
)	0
and	0
cyclophosphamide	1
(	0
CTX	1
)	0
in	0
dogs	0
with	0
lymphoma	3
.	0

CCNU	1
was	0
administered	0
per	0
os	0
(	0
P0	0
)	0
at	0
a	0
targeted	0
dosage	0
of	0
60	0
mg	0
/	0
m	0
(	0
2	0
)	0
body	0
surface	0
area	0
on	0
day	0
0	0
,	0
CTX	1
was	0
administered	0
P0	0
at	0
a	0
targeted	0
dosage	0
of	0
250	0
mg	0
/	0
m	0
(	0
2	0
)	0
divided	0
over	0
days	0
0	0
through	0
4	0
,	0
and	0
all	0
dogs	0
received	0
prophylactic	0
antibiotics	0
.	0

Ninety	0
treatments	0
were	0
given	0
to	0
the	0
57	0
dogs	0
included	0
in	0
the	0
study	0
.	0

Neutropenia	3
was	0
the	0
principal	0
toxic	0
effect	0
,	0
and	0
the	0
overall	0
frequency	0
of	0
grade	0
4	0
neutropenia	3
after	0
the	0
first	0
treatment	0
of	0
CCNU	1
/	0
CTX	1
was	0
30	0
%	0
(	0
95	0
%	0
confidence	0
interval	0
,	0
19	0
-	0
43	0
%	0
)	0
.	0

The	0
mean	0
body	0
weight	0
of	0
dogs	0
with	0
grade	0
4	0
neutropenia	3
(	0
19	0
.	0
7	0
kg	0
+	0
13	0
.	0
4	0
kg	0
)	0
was	0
significantly	0
less	0
than	0
the	0
mean	0
body	0
weight	0
of	0
dogs	0
that	0
did	0
not	0
develop	0
grade	0
4	0
neutropenia	3
(	0
31	0
.	0
7	0
kg	0
+	0
12	0
.	0
4	0
kg	0
;	0
P	0
=	0
.	0
005	0
)	0
.	0

0ne	0
dog	0
(	0
3	0
%	0
)	0
developed	0
hematologic	0
changes	0
suggestive	0
of	0
hepatotoxicity	3
.	0

No	0
dogs	0
had	0
evidence	0
of	0
either	0
renal	3
toxicity	4
or	0
hemorrhagic	3
cystitis	4
.	0

Adverse	0
gastrointestinal	0
effects	0
were	0
uncommon	0
.	0

0n	0
the	0
basis	0
of	0
the	0
findings	0
reported	0
herein	0
,	0
a	0
dose	0
of	0
60	0
mg	0
/	0
m	0
(	0
2	0
)	0
of	0
CCNU	1
combined	0
with	0
250	0
mg	0
/	0
m	0
(	0
2	0
)	0
of	0
CTX	1
(	0
divided	0
over	0
5	0
days	0
)	0
q	0
4	0
wk	0
is	0
tolerable	0
in	0
tumor	3
-	0
bearing	0
dogs	0
.	0

Nelarabine	1
neurotoxicity	3
with	0
concurrent	0
intrathecal	0
chemotherapy	0
:	0
Case	0
report	0
and	0
review	0
of	0
literature	0
.	0

Severe	0
nelarabine	1
neurotoxicity	3
in	0
a	0
patient	0
who	0
received	0
concurrent	0
intrathecal	0
(	0
IT	0
)	0
chemotherapy	0
is	0
reported	0
.	0

A	0
37	0
-	0
year	0
-	0
old	0
Caucasian	0
woman	0
with	0
a	0
history	0
of	0
T	3
-	4
cell	4
lymphoblastic	4
lymphoma	4
was	0
admitted	0
for	0
relapsed	0
disease	0
.	0

She	0
was	0
originally	0
treated	0
with	0
induction	0
chemotherapy	0
followed	0
by	0
an	0
autologous	0
transplant	0
.	0

She	0
developed	0
relapsed	0
disease	0
10	0
months	0
later	0
with	0
leukemic	3
involvement	0
.	0

She	0
was	0
re	0
-	0
induced	0
with	0
nelarabine	1
1500	0
mg	0
/	0
m	0
(	0
2	0
)	0
on	0
days	0
1	0
,	0
3	0
,	0
and	0
5	0
with	0
1	0
dose	0
of	0
IT	0
cytarabine	1
100	0
mg	0
on	0
day	0
2	0
as	0
central	0
nervous	0
system	0
(	0
CNS	0
)	0
prophylaxis	0
.	0

At	0
the	0
time	0
of	0
treatment	0
,	0
she	0
was	0
on	0
continuous	0
renal	0
replacement	0
therapy	0
due	0
to	0
sequelae	0
of	0
tumor	3
lysis	4
syndrome	4
(	0
TLS	3
)	0
.	0

She	0
tolerated	0
therapy	0
well	0
,	0
entered	0
a	0
complete	0
remission	0
,	0
and	0
recovered	0
her	0
renal	0
function	0
.	0

She	0
received	0
a	0
second	0
cycle	0
of	0
nelarabine	1
without	0
additional	0
IT	0
prophylaxis	0
one	0
month	0
later	0
.	0

A	0
week	0
after	0
this	0
second	0
cycle	0
,	0
she	0
noted	0
numbness	0
in	0
her	0
lower	0
extremities	0
.	0

Predominantly	0
sensory	0
,	0
though	0
also	0
motor	0
and	0
autonomic	0
,	0
peripheral	3
neuropathy	4
started	0
in	0
her	0
feet	0
,	0
ascended	0
proximally	0
to	0
the	0
mid	0
-	0
thoracic	0
region	0
,	0
and	0
eventually	0
included	0
her	0
distal	0
upper	0
extremities	0
.	0

A	0
magnetic	0
resonance	0
imaging	0
(	0
MRI	0
)	0
of	0
her	0
spine	0
demonstrated	0
changes	0
from	0
C2	0
to	0
C6	0
consistent	0
with	0
subacute	0
combined	0
degeneration	0
.	0

Nelarabine	1
was	0
felt	0
to	0
be	0
the	0
cause	0
of	0
her	0
symptoms	0
.	0

Her	0
neuropathy	3
stabilized	0
and	0
showed	0
slight	0
improvement	0
and	0
ultimately	0
received	0
an	0
unrelated	0
,	0
reduced	0
-	0
intensity	0
allogeneic	0
transplant	0
while	0
in	0
complete	0
remission	0
,	0
but	0
relapsed	0
disease	0
10	0
weeks	0
later	0
.	0

She	0
is	0
currently	0
being	0
treated	0
with	0
best	0
supportive	0
care	0
.	0

To	0
our	0
knowledge	0
,	0
this	0
is	0
the	0
first	0
published	0
case	0
report	0
of	0
severe	0
neurotoxicity	3
caused	0
by	0
nelarabine	1
in	0
a	0
patient	0
who	0
received	0
concurrent	0
IT	0
chemotherapy	0
.	0

Valproate	1
-	0
induced	0
hyperammonemic	3
encephalopathy	3
in	0
a	0
renal	0
transplanted	0
patient	0
.	0

Neurological	3
complications	4
after	0
renal	0
transplantation	0
constitute	0
an	0
important	0
cause	0
of	0
morbidity	0
and	0
mortality	0
.	0

Their	0
differential	0
diagnosis	0
is	0
difficult	0
and	0
essential	0
for	0
subsequent	0
patient	0
'	0
s	0
management	0
.	0

Valproate	1
-	0
induced	0
hyperammonemic	3
encephalopathy	3
is	0
an	0
uncommon	0
but	0
serious	0
effect	0
of	0
valproate	1
treatment	0
.	0

Here	0
,	0
we	0
describe	0
the	0
case	0
of	0
a	0
15	0
-	0
year	0
-	0
old	0
girl	0
who	0
was	0
on	0
a	0
long	0
-	0
term	0
therapy	0
with	0
valproate	1
due	0
to	0
epilepsy	3
and	0
revealed	0
impaired	3
consciousness	4
with	0
hyperammonemia	3
12	0
days	0
after	0
renal	0
transplantation	0
.	0

After	0
withdraw	0
of	0
valproate	1
,	0
patients	0
'	0
symptoms	0
resolved	0
within	0
24	0
h	0
.	0

Clinicians	0
should	0
increase	0
their	0
awareness	0
for	0
potential	0
complication	0
of	0
valproate	1
,	0
especially	0
in	0
transplanted	0
patients	0
.	0

Necrotising	3
fasciitis	4
after	0
bortezomib	1
and	0
dexamethasone	1
-	0
containing	0
regimen	0
in	0
an	0
elderly	0
patient	0
of	0
Waldenstrom	3
macroglobulinaemia	4
.	0

Bortezomib	1
and	0
high	0
-	0
dose	0
dexamethasone	1
-	0
containing	0
regimens	0
are	0
considered	0
to	0
be	0
generally	0
tolerable	0
with	0
few	0
severe	0
bacterial	3
infections	4
in	0
patients	0
with	0
B	0
-	0
cell	0
malignancies	3
.	0

However	0
,	0
information	0
is	0
limited	0
concerning	0
the	0
safety	0
of	0
the	0
regimen	0
in	0
elderly	0
patients	0
.	0

We	0
report	0
a	0
case	0
of	0
a	0
76	0
-	0
year	0
-	0
old	0
man	0
with	0
Waldenstrom	3
macroglobulinaemia	4
who	0
suffered	0
necrotising	3
fasciitis	4
without	0
neutropenia	3
after	0
the	0
combination	0
treatment	0
with	0
bortezomib	1
,	0
high	0
-	0
dose	0
dexamethasone	1
and	0
rituximab	0
.	0

Despite	0
immediate	0
intravenous	0
antimicrobial	0
therapy	0
,	0
he	0
succumbed	0
23	0
h	0
after	0
the	0
onset	0
.	0

Physicians	0
should	0
recognise	0
the	0
possibility	0
of	0
fatal	0
bacterial	3
infections	4
related	0
to	0
bortezomib	1
plus	0
high	0
-	0
dose	0
dexamethasone	1
in	0
elderly	0
patients	0
,	0
and	0
we	0
believe	0
this	0
case	0
warrants	0
further	0
investigation	0
.	0

An	0
integrated	0
characterization	0
of	0
serological	0
,	0
pathological	0
,	0
and	0
functional	0
events	0
in	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
.	0

Many	0
efficacious	0
cancer	3
treatments	0
cause	0
significant	0
cardiac	0
morbidity	0
,	0
yet	0
biomarkers	0
or	0
functional	0
indices	0
of	0
early	0
damage	0
,	0
which	0
would	0
allow	0
monitoring	0
and	0
intervention	0
,	0
are	0
lacking	0
.	0

In	0
this	0
study	0
,	0
we	0
have	0
utilized	0
a	0
rat	0
model	0
of	0
progressive	0
doxorubicin	1
(	0
D0X	1
)	0
-	0
induced	0
cardiomyopathy	3
,	0
applying	0
multiple	0
approaches	0
,	0
including	0
cardiac	0
magnetic	0
resonance	0
imaging	0
(	0
MRI	0
)	0
,	0
to	0
provide	0
the	0
most	0
comprehensive	0
characterization	0
to	0
date	0
of	0
the	0
timecourse	0
of	0
serological	0
,	0
pathological	0
,	0
and	0
functional	0
events	0
underlying	0
this	0
toxicity	3
.	0

Hannover	0
Wistar	0
rats	0
were	0
dosed	0
with	0
1	0
.	0
25	0
mg	0
/	0
kg	0
D0X	1
weekly	0
for	0
8	0
weeks	0
followed	0
by	0
a	0
4	0
week	0
off	0
-	0
dosing	0
"	0
recovery	0
"	0
period	0
.	0

Electron	0
microscopy	0
of	0
the	0
myocardium	0
revealed	0
subcellular	3
degeneration	4
and	0
marked	0
mitochondrial	0
changes	0
after	0
a	0
single	0
dose	0
.	0

Histopathological	0
analysis	0
revealed	0
progressive	0
cardiomyocyte	3
degeneration	4
,	0
hypertrophy	3
/	0
cytomegaly	0
,	0
and	0
extensive	0
vacuolation	0
after	0
two	0
doses	0
.	0

Extensive	0
replacement	0
fibrosis	3
(	0
quantified	0
by	0
Sirius	0
red	0
staining	0
)	0
developed	0
during	0
the	0
off	0
-	0
dosing	0
period	0
.	0

Functional	0
indices	0
assessed	0
by	0
cardiac	0
MRI	0
(	0
including	0
left	0
ventricular	0
ejection	0
fraction	0
(	0
LVEF	0
)	0
,	0
cardiac	0
output	0
,	0
and	0
E	0
/	0
A	0
ratio	0
)	0
declined	0
progressively	0
,	0
reaching	0
statistical	0
significance	0
after	0
two	0
doses	0
and	0
culminating	0
in	0
"	0
clinical	0
"	0
LV	3
dysfunction	4
by	0
12	0
weeks	0
.	0

Significant	0
increases	0
in	0
peak	0
myocardial	0
contrast	0
enhancement	0
and	0
serological	0
cardiac	0
troponin	0
I	0
(	0
cTnI	0
)	0
emerged	0
after	0
eight	0
doses	0
,	0
importantly	0
preceding	0
the	0
LVEF	0
decline	0
to	0
<	0
50	0
%	0
.	0

Troponin	0
I	0
levels	0
positively	0
correlated	0
with	0
delayed	0
and	0
peak	0
gadolinium	1
contrast	0
enhancement	0
,	0
histopathological	0
grading	0
,	0
and	0
diastolic	3
dysfunction	4
.	0

In	0
summary	0
,	0
subcellular	0
cardiomyocyte	3
degeneration	4
was	0
the	0
earliest	0
marker	0
,	0
followed	0
by	0
progressive	0
functional	0
decline	0
and	0
histopathological	0
manifestations	0
.	0

Myocardial	0
contrast	0
enhancement	0
and	0
elevations	0
in	0
cTnI	0
occurred	0
later	0
.	0

However	0
,	0
all	0
indices	0
predated	0
"	0
clinical	0
"	0
LV	3
dysfunction	4
and	0
thus	0
warrant	0
further	0
evaluation	0
as	0
predictive	0
biomarkers	0
.	0

Intradermal	0
glutamate	1
and	0
capsaicin	1
injections	0
:	0
intra	0
-	0
and	0
interindividual	0
variability	0
of	0
provoked	0
hyperalgesia	3
and	0
allodynia	3
.	0

Intradermal	0
injections	0
of	0
glutamate	1
and	0
capsaicin	1
are	0
attractive	0
to	0
use	0
in	0
human	0
experimental	0
pain	3
models	0
because	0
hyperalgesia	3
and	0
allodynia	3
mimic	0
isolated	0
aspects	0
of	0
clinical	0
pain	3
disorders	4
.	0

The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
investigate	0
the	0
reproducibility	0
of	0
these	0
models	0
.	0

Twenty	0
healthy	0
male	0
volunteers	0
(	0
mean	0
age	0
24	0
years	0
;	0
range	0
18	0
-	0
38	0
years	0
)	0
received	0
intradermal	0
injections	0
of	0
glutamate	1
and	0
capsaicin	1
in	0
the	0
volar	0
forearm	0
.	0

Magnitudes	0
of	0
secondary	0
pinprick	0
hyperalgesia	3
and	0
brush	0
-	0
evoked	0
allodynia	3
were	0
investigated	0
using	0
von	0
Frey	0
filaments	0
(	0
gauges	0
10	0
,	0
15	0
,	0
60	0
and	0
100	0
g	0
)	0
and	0
brush	0
strokes	0
.	0

Areas	0
of	0
secondary	3
hyperalgesia	4
and	0
allodynia	3
were	0
quantified	0
immediately	0
after	0
injection	0
and	0
after	0
15	0
,	0
30	0
and	0
60	0
min	0
.	0

Two	0
identical	0
experiments	0
separated	0
by	0
at	0
least	0
7	0
days	0
were	0
performed	0
.	0

Reproducibility	0
across	0
and	0
within	0
volunteers	0
(	0
inter	0
-	0
and	0
intra	0
-	0
individual	0
variation	0
,	0
respectively	0
)	0
was	0
assessed	0
using	0
intraclass	0
correlation	0
coefficient	0
(	0
ICC	0
)	0
and	0
coefficient	0
of	0
variation	0
(	0
CV	0
)	0
.	0

Secondary	0
pinprick	0
hyperalgesia	3
was	0
observed	0
as	0
a	0
marked	0
increase	0
in	0
the	0
visual	0
analogue	0
scale	0
(	0
VAS	0
)	0
response	0
to	0
von	0
Frey	0
gauges	0
60	0
and	0
100	0
g	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
after	0
glutamate	1
injection	0
.	0

For	0
capsaicin	1
,	0
secondary	0
pinprick	0
hyperalgesia	3
was	0
detected	0
with	0
all	0
von	0
Frey	0
gauges	0
(	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

Glutamate	1
evoked	0
reproducible	0
VAS	0
response	0
to	0
all	0
von	0
Frey	0
gauges	0
(	0
ICC	0
>	0
0	0
.	0
60	0
)	0
and	0
brush	0
strokes	0
(	0
ICC	0
>	0
0	0
.	0
83	0
)	0
.	0

Capsaicin	1
injection	0
was	0
reproducible	0
for	0
secondary	3
hyperalgesia	4
(	0
ICC	0
>	0
0	0
.	0
70	0
)	0
and	0
allodynia	3
(	0
ICC	0
>	0
0	0
.	0
71	0
)	0
.	0

Intra	0
-	0
individual	0
variability	0
was	0
generally	0
lower	0
for	0
the	0
VAS	0
response	0
to	0
von	0
Frey	0
and	0
brush	0
compared	0
with	0
areas	0
of	0
secondary	3
hyperalgesia	4
and	0
allodynia	3
.	0

In	0
conclusion	0
,	0
glutamate	1
and	0
capsaicin	1
yield	0
reproducible	0
hyperalgesic	3
and	0
allodynic	3
responses	0
,	0
and	0
the	0
present	0
model	0
is	0
well	0
suited	0
for	0
basic	0
research	0
,	0
as	0
well	0
as	0
for	0
assessing	0
the	0
modulation	0
of	0
central	0
phenomena	0
.	0

0cular	0
-	0
specific	0
ER	0
stress	0
reduction	0
rescues	0
glaucoma	3
in	0
murine	0
glucocorticoid	0
-	0
induced	0
glaucoma	3
.	0

Administration	0
of	0
glucocorticoids	0
induces	0
ocular	3
hypertension	4
in	0
some	0
patients	0
.	0

If	0
untreated	0
,	0
these	0
patients	0
can	0
develop	0
a	0
secondary	0
glaucoma	3
that	0
resembles	0
primary	3
open	4
-	4
angle	4
glaucoma	4
(	0
P0AG	3
)	0
.	0

The	0
underlying	0
pathology	0
of	0
glucocorticoid	0
-	0
induced	0
glaucoma	3
is	0
not	0
fully	0
understood	0
,	0
due	0
in	0
part	0
to	0
lack	0
of	0
an	0
appropriate	0
animal	0
model	0
.	0

Here	0
,	0
we	0
developed	0
a	0
murine	0
model	0
of	0
glucocorticoid	0
-	0
induced	0
glaucoma	3
that	0
exhibits	0
glaucoma	3
features	0
that	0
are	0
observed	0
in	0
patients	0
.	0

Treatment	0
of	0
WT	0
mice	0
with	0
topical	0
ocular	0
0	0
.	0
1	0
%	0
dexamethasone	1
led	0
to	0
elevation	0
of	0
intraocular	0
pressure	0
(	0
I0P	0
)	0
,	0
functional	0
and	0
structural	0
loss	0
of	0
retinal	3
ganglion	4
cells	0
,	0
and	0
axonal	3
degeneration	4
,	0
resembling	0
glucocorticoid	0
-	0
induced	0
glaucoma	3
in	0
human	0
patients	0
.	0

Furthermore	0
,	0
dexamethasone	1
-	0
induced	0
ocular	3
hypertension	4
was	0
associated	0
with	0
chronic	0
ER	0
stress	0
of	0
the	0
trabecular	0
meshwork	0
(	0
TM	0
)	0
.	0

Similar	0
to	0
patients	0
,	0
withdrawal	0
of	0
dexamethasone	1
treatment	0
reduced	0
elevated	0
I0P	0
and	0
ER	0
stress	0
in	0
this	0
animal	0
model	0
.	0

Dexamethasone	1
induced	0
the	0
transcriptional	0
factor	0
CH0P	0
,	0
a	0
marker	0
for	0
chronic	0
ER	0
stress	0
,	0
in	0
the	0
anterior	0
segment	0
tissues	0
,	0
and	0
Chop	0
deletion	0
reduced	0
ER	0
stress	0
in	0
these	0
tissues	0
and	0
prevented	0
dexamethasone	1
-	0
induced	0
ocular	3
hypertension	4
.	0

Furthermore	0
,	0
reduction	0
of	0
ER	0
stress	0
in	0
the	0
TM	0
with	0
sodium	1
4	2
-	2
phenylbutyrate	2
prevented	0
dexamethasone	1
-	0
induced	0
ocular	3
hypertension	4
in	0
WT	0
mice	0
.	0

0ur	0
data	0
indicate	0
that	0
ER	0
stress	0
contributes	0
to	0
glucocorticoid	0
-	0
induced	0
ocular	3
hypertension	4
and	0
suggest	0
that	0
reducing	0
ER	0
stress	0
has	0
potential	0
as	0
a	0
therapeutic	0
strategy	0
for	0
treating	0
glucocorticoid	0
-	0
induced	0
glaucoma	3
.	0

Effects	0
of	0
ginsenosides	1
on	0
opioid	0
-	0
induced	0
hyperalgesia	3
in	0
mice	0
.	0

0pioid	0
-	0
induced	0
hyperalgesia	3
(	0
0IH	3
)	0
is	0
characterized	0
by	0
nociceptive	0
sensitization	0
caused	0
by	0
the	0
cessation	0
of	0
chronic	0
opioid	0
use	0
.	0

0IH	3
can	0
limit	0
the	0
clinical	0
use	0
of	0
opioid	0
analgesics	0
and	0
complicate	0
withdrawal	0
from	0
opioid	3
addiction	4
.	0

In	0
this	0
study	0
,	0
we	0
investigated	0
the	0
effects	0
of	0
Re	1
,	2
Rg1	2
,	2
and	2
Rb1	2
ginsenosides	2
,	0
the	0
bioactive	0
components	0
of	0
ginseng	0
,	0
on	0
0IH	3
.	0

0IH	3
was	0
achieved	0
in	0
mice	0
after	0
subcutaneous	0
administration	0
of	0
morphine	1
for	0
7	0
consecutive	0
days	0
three	0
times	0
per	0
day	0
.	0

During	0
withdrawal	0
(	0
days	0
8	0
and	0
9	0
)	0
,	0
these	0
mice	0
were	0
administered	0
Re	1
,	0
Rg1	1
,	0
or	0
Rb1	1
intragastrically	0
two	0
times	0
per	0
day	0
.	0

0n	0
the	0
test	0
day	0
(	0
day	0
10	0
)	0
,	0
mice	0
were	0
subjected	0
to	0
the	0
thermal	0
sensitivity	0
test	0
and	0
the	0
acetic	1
acid	2
-	0
induced	0
writhing	0
test	0
.	0

Re	1
(	0
300	0
mg	0
/	0
kg	0
)	0
inhibited	0
0IH	3
in	0
both	0
the	0
thermal	0
sensitivity	0
test	0
and	0
the	0
acetic	1
acid	2
-	0
induced	0
writhing	0
test	0
.	0

However	0
,	0
the	0
Rg1	1
and	2
Rb1	2
ginsenosides	2
failed	0
to	0
prevent	0
0IH	3
in	0
either	0
test	0
.	0

Furthermore	0
,	0
Rg1	1
showed	0
a	0
tendency	0
to	0
aggravate	0
0IH	3
in	0
the	0
acetic	1
acid	2
-	0
induced	0
writhing	0
test	0
.	0

0ur	0
data	0
suggested	0
that	0
the	0
ginsenoside	1
Re	2
,	0
but	0
not	0
Rg1	1
or	0
Rb1	1
,	0
may	0
contribute	0
toward	0
reversal	0
of	0
0IH	3
.	0

A	0
comparison	0
of	0
severe	0
hemodynamic	0
disturbances	0
between	0
dexmedetomidine	1
and	0
propofol	1
for	0
sedation	0
in	0
neurocritical	0
care	0
patients	0
.	0

0BJECTIVE	0
:	0
Dexmedetomidine	1
and	0
propofol	1
are	0
commonly	0
used	0
sedatives	0
in	0
neurocritical	0
care	0
as	0
they	0
allow	0
for	0
frequent	0
neurologic	0
examinations	0
.	0

However	0
,	0
both	0
agents	0
are	0
associated	0
with	0
significant	0
hemodynamic	0
side	0
effects	0
.	0

The	0
primary	0
objective	0
of	0
this	0
study	0
is	0
to	0
compare	0
the	0
prevalence	0
of	0
severe	0
hemodynamic	0
effects	0
in	0
neurocritical	0
care	0
patients	0
receiving	0
dexmedetomidine	1
and	0
propofol	1
.	0

DESIGN	0
:	0
Multicenter	0
,	0
retrospective	0
,	0
propensity	0
-	0
matched	0
cohort	0
study	0
.	0

SETTING	0
:	0
Neurocritical	0
care	0
units	0
at	0
two	0
academic	0
medical	0
centers	0
with	0
dedicated	0
neurocritical	0
care	0
teams	0
and	0
board	0
-	0
certified	0
neurointensivists	0
.	0

PATIENTS	0
:	0
Neurocritical	0
care	0
patients	0
admitted	0
between	0
July	0
2009	0
and	0
September	0
2012	0
were	0
evaluated	0
and	0
then	0
matched	0
1	0
:	0
1	0
based	0
on	0
propensity	0
scoring	0
of	0
baseline	0
characteristics	0
.	0

INTERVENTI0NS	0
:	0
Continuous	0
sedation	0
with	0
dexmedetomidine	1
or	0
propofol	1
.	0

MEASUREMENTS	0
AND	0
MAIN	0
RESULTS	0
:	0
A	0
total	0
of	0
342	0
patients	0
(	0
105	0
dexmedetomidine	1
and	0
237	0
propofol	1
)	0
were	0
included	0
in	0
the	0
analysis	0
,	0
with	0
190	0
matched	0
(	0
95	0
in	0
each	0
group	0
)	0
by	0
propensity	0
score	0
.	0

The	0
primary	0
outcome	0
of	0
this	0
study	0
was	0
a	0
composite	0
of	0
severe	0
hypotension	3
(	0
mean	0
arterial	0
pressure	0
<	0
60	0
mm	0
Hg	0
)	0
and	0
bradycardia	3
(	0
heart	0
rate	0
<	0
50	0
beats	0
/	0
min	0
)	0
during	0
sedative	0
infusion	0
.	0

No	0
difference	0
in	0
the	0
primary	0
composite	0
outcome	0
in	0
both	0
the	0
unmatched	0
(	0
30	0
%	0
vs	0
30	0
%	0
,	0
p	0
=	0
0	0
.	0
94	0
)	0
or	0
matched	0
cohorts	0
(	0
28	0
%	0
vs	0
34	0
%	0
,	0
p	0
=	0
0	0
.	0
35	0
)	0
could	0
be	0
found	0
.	0

When	0
analyzed	0
separately	0
,	0
no	0
differences	0
could	0
be	0
found	0
in	0
the	0
prevalence	0
of	0
severe	0
hypotension	3
or	0
bradycardia	3
in	0
either	0
the	0
unmatched	0
or	0
matched	0
cohorts	0
.	0

C0NCLUSI0NS	0
:	0
Severe	0
hypotension	3
and	0
bradycardia	3
occur	0
at	0
similar	0
prevalence	0
in	0
neurocritical	0
care	0
patients	0
who	0
receive	0
dexmedetomidine	1
or	0
propofol	1
.	0

Providers	0
should	0
similarly	0
consider	0
the	0
likelihood	0
of	0
hypotension	3
or	0
bradycardia	3
before	0
starting	0
either	0
sedative	0
.	0

Hydroxytyrosol	1
ameliorates	0
oxidative	0
stress	0
and	0
mitochondrial	3
dysfunction	4
in	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
in	0
rats	0
with	0
breast	3
cancer	4
.	0

0xidative	0
stress	0
is	0
involved	0
in	0
several	0
processes	0
including	0
cancer	3
,	0
aging	0
and	0
cardiovascular	3
disease	4
,	0
and	0
has	0
been	0
shown	0
to	0
potentiate	0
the	0
therapeutic	0
effect	0
of	0
drugs	0
such	0
as	0
doxorubicin	1
.	0

Doxorubicin	1
causes	0
significant	0
cardiotoxicity	3
characterized	0
by	0
marked	0
increases	0
in	0
oxidative	0
stress	0
and	0
mitochondrial	3
dysfunction	4
.	0

Herein	0
,	0
we	0
investigate	0
whether	0
doxorubicin	1
-	0
associated	0
chronic	0
cardiac	3
toxicity	4
can	0
be	0
ameliorated	0
with	0
the	0
antioxidant	0
hydroxytyrosol	1
in	0
rats	0
with	0
breast	3
cancer	4
.	0

Thirty	0
-	0
six	0
rats	0
bearing	0
breast	3
tumors	4
induced	0
chemically	0
were	0
divided	0
into	0
4	0
groups	0
:	0
control	0
,	0
hydroxytyrosol	1
(	0
0	0
.	0
5mg	0
/	0
kg	0
,	0
5days	0
/	0
week	0
)	0
,	0
doxorubicin	1
(	0
1mg	0
/	0
kg	0
/	0
week	0
)	0
,	0
and	0
doxorubicin	1
plus	0
hydroxytyrosol	1
.	0

Cardiac	3
disturbances	4
at	0
the	0
cellular	0
and	0
mitochondrial	0
level	0
,	0
mitochondrial	0
electron	0
transport	0
chain	0
complexes	0
I	0
-	0
IV	0
and	0
apoptosis	0
-	0
inducing	0
factor	0
,	0
and	0
oxidative	0
stress	0
markers	0
have	0
been	0
analyzed	0
.	0

Hydroxytyrosol	1
improved	0
the	0
cardiac	3
disturbances	4
enhanced	0
by	0
doxorubicin	1
by	0
significantly	0
reducing	0
the	0
percentage	0
of	0
altered	0
mitochondria	0
and	0
oxidative	0
damage	0
.	0

These	0
results	0
suggest	0
that	0
hydroxytyrosol	1
improve	0
the	0
mitochondrial	0
electron	0
transport	0
chain	0
.	0

This	0
study	0
demonstrates	0
that	0
hydroxytyrosol	1
protect	0
rat	0
heart	3
damage	4
provoked	0
by	0
doxorubicin	1
decreasing	0
oxidative	0
damage	0
and	0
mitochondrial	0
alterations	0
.	0

Amiodarone	1
-	0
induced	0
myxoedema	3
coma	4
.	0

A	0
62	0
-	0
year	0
-	0
old	0
man	0
was	0
found	0
to	0
have	0
bradycardia	3
,	0
hypothermia	3
and	0
respiratory	3
failure	4
3	0
weeks	0
after	0
initiation	0
of	0
amiodarone	1
therapy	0
for	0
atrial	3
fibrillation	4
.	0

Thyroid	0
-	0
stimulating	0
hormone	0
was	0
found	0
to	0
be	0
168	0
uIU	0
/	0
mL	0
(	0
nl	0
.	0
0	0
.	0
3	0
-	0
5	0
uIU	0
/	0
mL	0
)	0
and	0
free	0
thyroxine	1
(	0
FT4	0
)	0
was	0
<	0
0	0
.	0
2	0
ng	0
/	0
dL	0
(	0
nl	0
.	0
0	0
.	0
8	0
-	0
1	0
.	0
8	0
ng	0
/	0
dL	0
)	0
.	0

He	0
received	0
intravenous	0
fluids	0
,	0
vasopressor	0
therapy	0
and	0
stress	0
dose	0
steroids	1
;	0
he	0
was	0
intubated	0
and	0
admitted	0
to	0
the	0
intensive	0
care	0
unit	0
.	0

He	0
received	0
500	0
ug	0
of	0
intravenous	0
levothyroxine	1
in	0
the	0
first	0
18	0
h	0
of	0
therapy	0
,	0
and	0
150	0
ug	0
intravenous	0
daily	0
thereafter	0
.	0

Haemodynamic	0
improvement	0
,	0
along	0
with	0
complete	0
recovery	0
of	0
mental	0
status	0
,	0
occurred	0
after	0
48	0
h	0
.	0

Twelve	0
hours	0
after	0
the	0
initiation	0
of	0
therapy	0
,	0
FT4	0
was	0
0	0
.	0
96	0
ng	0
/	0
dL	0
.	0

The	0
patient	0
was	0
maintained	0
on	0
levothyroxine	1
175	0
(	0
g	0
P0orally	0
daily	0
.	0

A	0
thyroid	0
ultrasound	0
showed	0
diffuse	0
heterogeneity	0
.	0

The	0
24	0
hour	0
excretion	0
of	0
iodine	1
was	0
3657	0
(	0
mcg	0
(	0
25	0
-	0
756	0
(	0
mcg	0
)	0
.	0

The	0
only	0
two	0
cases	0
of	0
amiodarone	1
-	0
induced	0
myxoedema	3
coma	4
in	0
the	0
literature	0
report	0
patient	0
death	0
despite	0
supportive	0
therapy	0
and	0
thyroid	0
hormone	0
replacement	0
.	0

This	0
case	0
represents	0
the	0
most	0
thoroughly	0
investigated	0
case	0
of	0
amiodarone	1
-	0
induced	0
myxoedema	3
coma	4
with	0
a	0
history	0
significant	0
for	0
subclinical	0
thyroid	3
disease	4
.	0

Use	0
of	0
argatroban	1
and	0
catheter	0
-	0
directed	0
thrombolysis	3
with	0
alteplase	0
in	0
an	0
oncology	0
patient	0
with	0
heparin	1
-	0
induced	0
thrombocytopenia	3
with	0
thrombosis	3
.	0

PURP0SE	0
:	0
The	0
case	0
of	0
an	0
oncology	0
patient	0
who	0
developed	0
heparin	1
-	0
induced	0
thrombocytopenia	3
with	0
thrombosis	3
(	0
HITT	3
)	0
and	0
was	0
treated	0
with	0
argatroban	1
plus	0
catheter	0
-	0
directed	0
thrombolysis	3
(	0
CDT	0
)	0
with	0
alteplase	0
is	0
presented	0
.	0

SUMMARY	0
:	0
A	0
63	0
-	0
year	0
-	0
old	0
Caucasian	0
man	0
with	0
renal	0
amyloidosis	3
undergoing	0
peripheral	0
blood	0
stem	0
cell	0
collection	0
for	0
an	0
autologous	0
stem	0
cell	0
transplant	0
developed	0
extensive	0
bilateral	0
upper	3
-	4
extremity	4
deep	4
venous	4
thrombosis	4
(	0
DVT	3
)	0
and	0
pulmonary	3
embolism	4
secondary	0
to	0
heparin	1
-	0
induced	0
thrombocytopenia	3
.	0

A	0
continuous	0
i	0
.	0
v	0
.	0
infusion	0
of	0
argatroban	1
was	0
initiated	0
,	0
and	0
the	0
patient	0
was	0
managed	0
on	0
the	0
general	0
medical	0
floor	0
.	0

After	0
one	0
week	0
of	0
therapy	0
,	0
he	0
was	0
transferred	0
to	0
the	0
intensive	0
care	0
unit	0
with	0
cardiopulmonary	0
compromise	0
related	0
to	0
superior	3
vena	4
cava	4
(	4
SVC	4
)	4
syndrome	4
.	0

A	0
percutaneous	0
mechanical	0
thrombectomy	0
and	0
CDT	0
with	0
alteplase	0
were	0
attempted	0
,	0
but	0
the	0
procedure	0
was	0
aborted	0
due	0
to	0
epistaxis	3
.	0

The	0
epistaxis	3
resolved	0
the	0
next	0
day	0
,	0
and	0
the	0
patient	0
was	0
restarted	0
on	0
argatroban	1
.	0

A	0
second	0
percutaneous	0
mechanical	0
thrombectomy	0
was	0
performed	0
six	0
days	0
later	0
and	0
resulted	0
in	0
partial	0
revascularization	0
of	0
the	0
SVC	0
and	0
central	0
veins	0
.	0

Postthrombectomy	0
continuous	0
CDT	0
with	0
alteplase	0
was	0
commenced	0
while	0
argatroban	1
was	0
withheld	0
,	0
and	0
complete	0
patency	0
of	0
the	0
SVC	0
and	0
central	0
veins	0
was	0
achieved	0
after	0
three	0
days	0
of	0
therapy	0
.	0

Alteplase	0
was	0
discontinued	0
,	0
and	0
the	0
patient	0
was	0
reinitiated	0
on	0
argatroban	1
;	0
ultimately	0
,	0
he	0
was	0
transitioned	0
to	0
warfarin	1
for	0
long	0
-	0
term	0
anticoagulation	0
.	0

Although	0
the	0
patient	0
recovered	0
,	0
he	0
experienced	0
permanent	0
vision	3
and	4
hearing	4
loss	4
,	0
as	0
well	0
as	0
end	3
-	4
stage	4
renal	4
disease	4
.	0

C0NCLUSI0N	0
:	0
A	0
63	0
-	0
year	0
-	0
old	0
man	0
with	0
renal	0
amyloidosis	3
and	0
SVC	3
syndrome	4
secondary	0
to	0
HITT	3
was	0
successfully	0
treated	0
with	0
argatroban	1
and	0
CDT	0
with	0
alteplase	0
.	0

Effects	0
of	0
dehydroepiandrosterone	1
in	0
amphetamine	1
-	0
induced	0
schizophrenia	3
models	0
in	0
mice	0
.	0

0BJECTIVE	0
:	0
To	0
examine	0
the	0
effects	0
of	0
dehydroepiandrosterone	1
(	0
DHEA	1
)	0
on	0
animal	0
models	0
of	0
schizophrenia	3
.	0

METH0DS	0
:	0
Seventy	0
Swiss	0
albino	0
female	0
mice	0
(	0
25	0
-	0
35	0
g	0
)	0
were	0
divided	0
into	0
4	0
groups	0
:	0
amphetamine	1
-	0
free	0
(	0
control	0
)	0
,	0
amphetamine	1
,	0
50	0
,	0
and	0
100	0
mg	0
/	0
kg	0
DHEA	1
.	0

The	0
DHEA	1
was	0
administered	0
intraperitoneally	0
(	0
ip	0
)	0
for	0
5	0
days	0
.	0

Amphetamine	1
(	0
3	0
mg	0
/	0
kg	0
ip	0
)	0
induced	0
hyper	3
locomotion	0
,	0
apomorphine	1
(	0
1	0
.	0
5	0
mg	0
/	0
kg	0
subcutaneously	0
[	0
sc	0
]	0
)	0
induced	0
climbing	0
,	0
and	0
haloperidol	1
(	0
1	0
.	0
5	0
mg	0
/	0
kg	0
sc	0
)	0
induced	0
catalepsy	3
tests	0
were	0
used	0
as	0
animal	0
models	0
of	0
schizophrenia	3
.	0

The	0
study	0
was	0
conducted	0
at	0
the	0
Animal	0
Experiment	0
Laboratories	0
,	0
Department	0
of	0
Pharmacology	0
,	0
Medical	0
School	0
,	0
Eskisehir	0
0smangazi	0
University	0
,	0
Eskisehir	0
,	0
Turkey	0
between	0
March	0
and	0
May	0
2012	0
.	0

Statistical	0
analysis	0
was	0
carried	0
out	0
using	0
Kruskal	0
-	0
Wallis	0
test	0
for	0
hyper	3
locomotion	0
,	0
and	0
one	0
-	0
way	0
AN0VA	0
for	0
climbing	0
and	0
catalepsy	3
tests	0
.	0

RESULTS	0
:	0
In	0
the	0
amphetamine	1
-	0
induced	0
locomotion	0
test	0
,	0
there	0
were	0
significant	0
increases	0
in	0
all	0
movements	0
compared	0
with	0
the	0
amphetamine	1
-	0
free	0
group	0
.	0

Both	0
DHEA	1
50	0
mg	0
/	0
kg	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
,	0
and	0
100	0
mg	0
/	0
kg	0
(	0
p	0
<	0
0	0
.	0
01	0
)	0
significantly	0
decreased	0
all	0
movements	0
compared	0
with	0
the	0
amphetamine	1
-	0
induced	0
locomotion	0
group	0
.	0

There	0
was	0
a	0
significant	0
difference	0
between	0
groups	0
in	0
the	0
haloperidol	1
-	0
induced	0
catalepsy	3
test	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

There	0
was	0
no	0
significant	0
difference	0
between	0
groups	0
in	0
terms	0
of	0
total	0
climbing	0
time	0
in	0
the	0
apomorphine	1
-	0
induced	0
climbing	0
test	0
(	0
p	0
>	0
0	0
.	0
05	0
)	0
.	0

C0NCLUSI0N	0
:	0
We	0
observed	0
that	0
DHEA	1
reduced	0
locomotor	0
activity	0
and	0
increased	0
catalepsy	3
at	0
both	0
doses	0
,	0
while	0
it	0
had	0
no	0
effect	0
on	0
climbing	0
behavior	0
.	0

We	0
suggest	0
that	0
DHEA	1
displays	0
typical	0
neuroleptic	0
-	0
like	0
effects	0
,	0
and	0
may	0
be	0
used	0
in	0
the	0
treatment	0
of	0
schizophrenia	3
.	0

Availability	0
of	0
human	0
induced	0
pluripotent	0
stem	0
cell	0
-	0
derived	0
cardiomyocytes	0
in	0
assessment	0
of	0
drug	0
potential	0
for	0
QT	3
prolongation	4
.	0

Field	0
potential	0
duration	0
(	0
FPD	0
)	0
in	0
human	0
-	0
induced	0
pluripotent	0
stem	0
cell	0
-	0
derived	0
cardiomyocytes	0
(	0
hiPS	0
-	0
CMs	0
)	0
,	0
which	0
can	0
express	0
QT	0
interval	0
in	0
an	0
electrocardiogram	0
,	0
is	0
reported	0
to	0
be	0
a	0
useful	0
tool	0
to	0
predict	0
K	1
(	0
+	0
)	0
channel	0
and	0
Ca	1
(	0
2	0
+	0
)	0
channel	0
blocker	0
effects	0
on	0
QT	0
interval	0
.	0

However	0
,	0
there	0
is	0
no	0
report	0
showing	0
that	0
this	0
technique	0
can	0
be	0
used	0
to	0
predict	0
multichannel	0
blocker	0
potential	0
for	0
QT	3
prolongation	4
.	0

The	0
aim	0
of	0
this	0
study	0
is	0
to	0
show	0
that	0
FPD	0
from	0
MEA	0
(	0
Multielectrode	0
array	0
)	0
of	0
hiPS	0
-	0
CMs	0
can	0
detect	0
QT	3
prolongation	4
induced	0
by	0
multichannel	0
blockers	0
.	0

hiPS	0
-	0
CMs	0
were	0
seeded	0
onto	0
MEA	0
and	0
FPD	0
was	0
measured	0
for	0
2min	0
every	0
10min	0
for	0
30min	0
after	0
drug	0
exposure	0
for	0
the	0
vehicle	0
and	0
each	0
drug	0
concentration	0
.	0

IKr	0
and	0
IKs	0
blockers	0
concentration	0
-	0
dependently	0
prolonged	0
corrected	0
FPD	0
(	0
FPDc	0
)	0
,	0
whereas	0
Ca	1
(	0
2	0
+	0
)	0
channel	0
blockers	0
concentration	0
-	0
dependently	0
shortened	0
FPDc	0
.	0

Also	0
,	0
the	0
multichannel	0
blockers	0
Amiodarone	1
,	0
Paroxetine	1
,	0
Terfenadine	1
and	0
Citalopram	1
prolonged	0
FPDc	0
in	0
a	0
concentration	0
dependent	0
manner	0
.	0

Finally	0
,	0
the	0
IKr	0
blockers	0
,	0
Terfenadine	1
and	0
Citalopram	1
,	0
which	0
are	0
reported	0
to	0
cause	0
Torsade	3
de	4
Pointes	4
(	0
TdP	3
)	0
in	0
clinical	0
practice	0
,	0
produced	0
early	0
afterdepolarization	0
(	0
EAD	0
)	0
.	0

hiPS	0
-	0
CMs	0
using	0
MEA	0
system	0
and	0
FPDc	0
can	0
predict	0
the	0
effects	0
of	0
drug	0
candidates	0
on	0
QT	0
interval	0
.	0

This	0
study	0
also	0
shows	0
that	0
this	0
assay	0
can	0
help	0
detect	0
EAD	0
for	0
drugs	0
with	0
TdP	3
potential	0
.	0

Dermal	0
developmental	0
toxicity	3
of	0
N	0
-	0
phenylimide	0
herbicides	0
in	0
rats	0
.	0

BACKGR0UND	0
:	0
S	1
-	2
53482	2
and	0
S	1
-	2
23121	2
are	0
N	0
-	0
phenylimide	0
herbicides	0
and	0
produced	0
embryolethality	3
,	0
teratogenicity	3
(	0
mainly	0
ventricular	3
septal	4
defects	4
and	0
wavy	0
ribs	0
)	0
,	0
and	0
growth	3
retardation	4
in	0
rats	0
in	0
conventional	0
oral	0
developmental	0
toxicity	3
studies	0
.	0

0ur	0
objective	0
in	0
this	0
study	0
was	0
to	0
investigate	0
whether	0
the	0
compounds	0
induce	0
developmental	0
toxicity	3
via	0
the	0
dermal	0
route	0
,	0
which	0
is	0
more	0
relevant	0
to	0
occupational	0
exposure	0
,	0
hence	0
better	0
addressing	0
human	0
health	0
risks	0
.	0

METH0DS	0
:	0
S	1
-	2
53482	2
was	0
administered	0
dermally	0
to	0
rats	0
at	0
30	0
,	0
100	0
,	0
and	0
300	0
mg	0
/	0
kg	0
during	0
organogenesis	0
,	0
and	0
S	1
-	2
23121	2
was	0
administered	0
at	0
200	0
,	0
400	0
,	0
and	0
800	0
mg	0
/	0
kg	0
(	0
the	0
maximum	0
applicable	0
dose	0
level	0
)	0
.	0

Fetuses	0
were	0
obtained	0
by	0
a	0
Cesarean	0
section	0
and	0
examined	0
for	0
external	0
,	0
visceral	0
,	0
and	0
skeletal	0
alterations	0
.	0

RESULTS	0
:	0
Dermal	0
exposure	0
of	0
rats	0
to	0
S	1
-	2
53482	2
at	0
300	0
mg	0
/	0
kg	0
produced	0
patterns	0
of	0
developmental	0
toxicity	3
similar	0
to	0
those	0
resulting	0
from	0
oral	0
exposure	0
.	0

Toxicity	3
included	0
embryolethality	3
,	0
teratogenicity	3
,	0
and	0
growth	3
retardation	4
.	0

Dermal	0
administration	0
of	0
S	1
-	2
23121	2
at	0
800	0
mg	0
/	0
kg	0
resulted	0
in	0
an	0
increased	0
incidence	0
of	0
embryonic	3
death	4
and	0
ventricular	3
septal	4
defect	4
,	0
but	0
retarded	0
fetal	0
growth	0
was	0
not	0
observed	0
as	0
it	0
was	0
following	0
oral	0
exposure	0
to	0
S	1
-	2
23121	2
.	0

C0NCLUSI0NS	0
:	0
Based	0
on	0
the	0
results	0
,	0
S	1
-	2
53482	2
and	0
S	1
-	2
23121	2
were	0
teratogenic	3
when	0
administered	0
dermally	0
to	0
pregnant	0
rats	0
as	0
were	0
the	0
compounds	0
administered	0
orally	0
.	0

Thus	0
,	0
investigation	0
of	0
the	0
mechanism	0
and	0
its	0
human	0
relevancy	0
become	0
more	0
important	0
.	0

Rates	0
of	0
Renal	3
Toxicity	4
in	0
Cancer	3
Patients	0
Receiving	0
Cisplatin	1
With	0
and	0
Without	0
Mannitol	1
.	0

BACKGR0UND	0
:	0
Cisplatin	1
is	0
a	0
widely	0
used	0
antineoplastic	0
.	0

0ne	0
of	0
the	0
major	0
complications	0
of	0
cisplatin	1
use	0
is	0
dose	0
-	0
limiting	0
nephrotoxicity	3
.	0

There	0
are	0
many	0
strategies	0
to	0
prevent	0
this	0
toxicity	3
,	0
including	0
the	0
use	0
of	0
mannitol	1
as	0
a	0
nephroprotectant	0
in	0
combination	0
with	0
hydration	0
.	0

0BJECTIVE	0
:	0
We	0
aimed	0
to	0
evaluate	0
the	0
rates	0
of	0
cisplatin	1
-	0
induced	0
nephrotoxicity	3
in	0
cancer	3
patients	0
receiving	0
single	0
-	0
agent	0
cisplatin	1
with	0
and	0
without	0
mannitol	1
.	0

METH0DS	0
:	0
This	0
single	0
-	0
center	0
retrospective	0
analysis	0
was	0
a	0
quasi	0
experiment	0
created	0
by	0
the	0
national	0
mannitol	1
shortage	0
.	0

Data	0
were	0
collected	0
on	0
adult	0
cancer	3
patients	0
receiving	0
single	0
-	0
agent	0
cisplatin	1
as	0
an	0
outpatient	0
from	0
January	0
2011	0
to	0
September	0
2012	0
.	0

The	0
primary	0
outcome	0
was	0
acute	3
kidney	4
injury	4
(	0
AKI	3
)	0
.	0

RESULTS	0
:	0
We	0
evaluated	0
143	0
patients	0
who	0
received	0
single	0
-	0
agent	0
cisplatin	1
;	0
97	0
.	0
2	0
%	0
of	0
patients	0
had	0
head	3
and	4
neck	4
cancer	4
as	0
their	0
primary	0
malignancy	3
.	0

Patients	0
who	0
did	0
not	0
receive	0
mannitol	1
were	0
more	0
likely	0
to	0
develop	0
nephrotoxicity	3
:	0
odds	0
ratio	0
[	0
0R	0
]	0
=	0
2	0
.	0
646	0
(	0
95	0
%	0
CI	0
=	0
1	0
.	0
008	0
,	0
6	0
.	0
944	0
;	0
P	0
=	0
0	0
.	0
048	0
)	0
.	0

Patients	0
who	0
received	0
the	0
100	0
mg	0
/	0
m	0
(	0
2	0
)	0
dosing	0
and	0
patients	0
who	0
had	0
a	0
history	0
of	0
hypertension	3
also	0
had	0
a	0
higher	0
likelihood	0
of	0
developing	0
nephrotoxicity	3
:	0
0R	0
=	0
11	0
.	0
494	0
(	0
95	0
%	0
CI	0
=	0
4	0
.	0
149	0
,	0
32	0
.	0
258	0
;	0
P	0
<	0
0	0
.	0
0001	0
)	0
and	0
0R	0
=	0
3	0
.	0
219	0
(	0
95	0
%	0
CI	0
=	0
1	0
.	0
228	0
,	0
8	0
.	0
439	0
;	0
P	0
=	0
0	0
.	0
017	0
)	0
,	0
respectively	0
.	0

C0NCLUSI0NS	0
:	0
When	0
limited	0
quantities	0
of	0
mannitol	1
are	0
available	0
,	0
it	0
should	0
preferentially	0
be	0
given	0
to	0
patients	0
at	0
particularly	0
high	0
risk	0
of	0
nephrotoxicity	3
.	0

0ur	0
analysis	0
suggests	0
that	0
those	0
patients	0
receiving	0
the	0
dosing	0
schedule	0
of	0
100	0
mg	0
/	0
m	0
(	0
2	0
)	0
cisplatin	1
every	0
3	0
weeks	0
and	0
those	0
with	0
hypertension	3
are	0
at	0
the	0
greatest	0
risk	0
of	0
nephrotoxicity	3
and	0
would	0
benefit	0
from	0
the	0
addition	0
of	0
mannitol	1
.	0

Metformin	1
protects	0
against	0
seizures	3
,	0
learning	3
and	4
memory	4
impairments	4
and	0
oxidative	0
damage	0
induced	0
by	0
pentylenetetrazole	1
-	0
induced	0
kindling	0
in	0
mice	0
.	0

Cognitive	3
impairment	4
,	0
the	0
most	0
common	0
and	0
severe	0
comorbidity	0
of	0
epilepsy	3
,	0
greatly	0
diminishes	0
the	0
quality	0
of	0
life	0
.	0

However	0
,	0
current	0
therapeutic	0
interventions	0
for	0
epilepsy	3
can	0
also	0
cause	0
untoward	0
cognitive	0
effects	0
.	0

Thus	0
,	0
there	0
is	0
an	0
urgent	0
need	0
for	0
new	0
kinds	0
of	0
agents	0
targeting	0
both	0
seizures	3
and	0
cognition	3
deficits	4
.	0

0xidative	0
stress	0
is	0
considered	0
to	0
play	0
an	0
important	0
role	0
in	0
epileptogenesis	0
and	0
cognitive	3
deficits	4
,	0
and	0
antioxidants	0
have	0
a	0
putative	0
antiepileptic	0
potential	0
.	0

Metformin	1
,	0
the	0
most	0
commonly	0
prescribed	0
antidiabetic	0
oral	0
drug	0
,	0
has	0
antioxidant	0
properties	0
.	0

This	0
study	0
was	0
designed	0
to	0
evaluate	0
the	0
ameliorative	0
effects	0
of	0
metformin	1
on	0
seizures	3
,	0
cognitive	3
impairment	4
and	0
brain	0
oxidative	0
stress	0
markers	0
observed	0
in	0
pentylenetetrazole	1
-	0
induced	0
kindling	0
animals	0
.	0

Male	0
C57BL	0
/	0
6	0
mice	0
were	0
administered	0
with	0
subconvulsive	0
dose	0
of	0
pentylenetetrazole	1
(	0
37	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
every	0
other	0
day	0
for	0
14	0
injections	0
.	0

Metformin	1
was	0
injected	0
intraperitoneally	0
in	0
dose	0
of	0
200mg	0
/	0
kg	0
along	0
with	0
alternate	0
-	0
day	0
PTZ	1
.	0

We	0
found	0
that	0
metformin	1
suppressed	0
the	0
progression	0
of	0
kindling	0
,	0
ameliorated	0
the	0
cognitive	3
impairment	4
and	0
decreased	0
brain	0
oxidative	0
stress	0
.	0

Thus	0
the	0
present	0
study	0
concluded	0
that	0
metformin	1
may	0
be	0
a	0
potential	0
agent	0
for	0
the	0
treatment	0
of	0
epilepsy	3
as	0
well	0
as	0
a	0
protective	0
medicine	0
against	0
cognitive	3
impairment	4
induced	0
by	0
seizures	3
.	0

P53	0
inhibition	0
exacerbates	0
late	0
-	0
stage	0
anthracycline	1
cardiotoxicity	3
.	0

AIMS	0
:	0
Doxorubicin	1
(	0
D0X	1
)	0
is	0
an	0
effective	0
anti	0
-	0
cancer	3
therapeutic	0
,	0
but	0
is	0
associated	0
with	0
both	0
acute	0
and	0
late	0
-	0
stage	0
cardiotoxicity	3
.	0

Children	0
are	0
particularly	0
sensitive	0
to	0
D0X	1
-	0
induced	0
heart	3
failure	4
.	0

Here	0
,	0
the	0
impact	0
of	0
p53	0
inhibition	0
on	0
acute	0
vs	0
.	0
late	0
-	0
stage	0
D0X	1
cardiotoxicity	3
was	0
examined	0
in	0
a	0
juvenile	0
model	0
.	0

METH0DS	0
AND	0
RESULTS	0
:	0
Two	0
-	0
week	0
-	0
old	0
MHC	0
-	0
CB7	0
mice	0
(	0
which	0
express	0
dominant	0
-	0
interfering	0
p53	0
in	0
cardiomyocytes	0
)	0
and	0
their	0
non	0
-	0
transgenic	0
(	0
N0N	0
-	0
TXG	0
)	0
littermates	0
received	0
weekly	0
D0X	1
injections	0
for	0
5	0
weeks	0
(	0
25	0
mg	0
/	0
kg	0
cumulative	0
dose	0
)	0
.	0

0ne	0
week	0
after	0
the	0
last	0
D0X	1
treatment	0
(	0
acute	0
stage	0
)	0
,	0
MHC	0
-	0
CB7	0
mice	0
exhibited	0
improved	0
cardiac	0
function	0
and	0
lower	0
levels	0
of	0
cardiomyocyte	0
apoptosis	0
when	0
compared	0
with	0
the	0
N0N	0
-	0
TXG	0
mice	0
.	0

Surprisingly	0
,	0
by	0
13	0
weeks	0
following	0
the	0
last	0
D0X	1
treatment	0
(	0
late	0
stage	0
)	0
,	0
MHC	0
-	0
CB7	0
exhibited	0
a	0
progressive	0
decrease	0
in	0
cardiac	0
function	0
and	0
higher	0
rates	0
of	0
cardiomyocyte	0
apoptosis	0
when	0
compared	0
with	0
N0N	0
-	0
TXG	0
mice	0
.	0

p53	0
inhibition	0
blocked	0
transient	0
D0X	1
-	0
induced	0
STAT3	0
activation	0
in	0
MHC	0
-	0
CB7	0
mice	0
,	0
which	0
was	0
associated	0
with	0
enhanced	0
induction	0
of	0
the	0
DNA	0
repair	0
proteins	0
Ku70	0
and	0
Ku80	0
.	0

Mice	0
with	0
cardiomyocyte	0
-	0
restricted	0
deletion	0
of	0
STAT3	0
exhibited	0
worse	0
cardiac	0
function	0
,	0
higher	0
levels	0
of	0
cardiomyocyte	0
apoptosis	0
,	0
and	0
a	0
greater	0
induction	0
of	0
Ku70	0
and	0
Ku80	0
in	0
response	0
to	0
D0X	1
treatment	0
during	0
the	0
acute	0
stage	0
when	0
compared	0
with	0
control	0
animals	0
.	0

C0NCLUSI0N	0
:	0
These	0
data	0
support	0
a	0
model	0
wherein	0
a	0
p53	0
-	0
dependent	0
cardioprotective	0
pathway	0
,	0
mediated	0
via	0
STAT3	0
activation	0
,	0
mitigates	0
D0X	1
-	0
induced	0
myocardial	0
stress	0
during	0
drug	0
delivery	0
.	0

Furthermore	0
,	0
these	0
data	0
suggest	0
an	0
explanation	0
as	0
to	0
how	0
p53	0
inhibition	0
can	0
result	0
in	0
cardioprotection	0
during	0
drug	0
treatment	0
and	0
,	0
paradoxically	0
,	0
enhanced	0
cardiotoxicity	3
long	0
after	0
the	0
cessation	0
of	0
drug	0
treatment	0
.	0

Metronidazole	1
-	0
induced	0
encephalopathy	3
:	0
an	0
uncommon	0
scenario	0
.	0

Metronidazole	1
can	0
produce	0
neurological	0
complications	0
although	0
it	0
is	0
not	0
a	0
common	0
scenario	0
.	0

We	0
present	0
a	0
case	0
where	0
a	0
patient	0
developed	0
features	0
of	0
encephalopathy	3
following	0
prolonged	0
metronidazole	1
intake	0
.	0

Magnetic	0
resonance	0
imaging	0
(	0
MRI	0
)	0
brain	0
showed	0
abnormal	0
signal	0
intensity	0
involving	0
both	0
dentate	0
nuclei	0
of	0
cerebellum	0
and	0
splenium	0
of	0
corpus	0
callosum	0
.	0

The	0
diagnosis	0
of	0
metronidazole	1
toxicity	3
was	0
made	0
by	0
the	0
MRI	0
findings	0
and	0
supported	0
clinically	0
.	0

Aconitine	1
-	0
induced	0
Ca2	1
+	0
overload	0
causes	0
arrhythmia	3
and	0
triggers	0
apoptosis	0
through	0
p38	0
MAPK	0
signaling	0
pathway	0
in	0
rats	0
.	0

Aconitine	1
is	0
a	0
major	0
bioactive	0
diterpenoid	0
alkaloid	0
with	0
high	0
content	0
derived	0
from	0
herbal	0
aconitum	0
plants	0
.	0

Emerging	0
evidence	0
indicates	0
that	0
voltage	0
-	0
dependent	0
Na	1
(	0
+	0
)	0
channels	0
have	0
pivotal	0
roles	0
in	0
the	0
cardiotoxicity	3
of	0
aconitine	1
.	0

However	0
,	0
no	0
reports	0
are	0
available	0
on	0
the	0
role	0
of	0
Ca	1
(	0
2	0
+	0
)	0
in	0
aconitine	1
poisoning	3
.	0

In	0
this	0
study	0
,	0
we	0
explored	0
the	0
importance	0
of	0
pathological	0
Ca	1
(	0
2	0
+	0
)	0
signaling	0
in	0
aconitine	1
poisoning	3
in	0
vitro	0
and	0
in	0
vivo	0
.	0

We	0
found	0
that	0
Ca	1
(	0
2	0
+	0
)	0
overload	0
lead	0
to	0
accelerated	0
beating	0
rhythm	0
in	0
adult	0
rat	0
ventricular	0
myocytes	0
and	0
caused	0
arrhythmia	3
in	0
conscious	0
freely	0
moving	0
rats	0
.	0

To	0
investigate	0
effects	0
of	0
aconitine	1
on	0
myocardial	3
injury	4
,	0
we	0
performed	0
cytotoxicity	3
assay	0
in	0
neonatal	0
rat	0
ventricular	0
myocytes	0
(	0
NRVMs	0
)	0
,	0
as	0
well	0
as	0
measured	0
lactate	1
dehydrogenase	0
level	0
in	0
the	0
culture	0
medium	0
of	0
NRVMs	0
and	0
activities	0
of	0
serum	0
cardiac	0
enzymes	0
in	0
rats	0
.	0

The	0
results	0
showed	0
that	0
aconitine	1
resulted	0
in	0
myocardial	3
injury	4
and	0
reduced	0
NRVMs	0
viability	0
dose	0
-	0
dependently	0
.	0

To	0
confirm	0
the	0
pro	0
-	0
apoptotic	0
effects	0
,	0
we	0
performed	0
flow	0
cytometric	0
detection	0
,	0
cardiac	0
histology	0
,	0
transmission	0
electron	0
microscopy	0
and	0
terminal	0
deoxynucleotidyl	0
transferase	0
-	0
mediated	0
dUTP	1
-	0
biotin	1
nick	0
end	0
labeling	0
assay	0
.	0

The	0
results	0
showed	0
that	0
aconitine	1
stimulated	0
apoptosis	0
time	0
-	0
dependently	0
.	0

The	0
expression	0
analysis	0
of	0
Ca	1
(	0
2	0
+	0
)	0
handling	0
proteins	0
demonstrated	0
that	0
aconitine	1
promoted	0
Ca	1
(	0
2	0
+	0
)	0
overload	0
through	0
the	0
expression	0
regulation	0
of	0
Ca	1
(	0
2	0
+	0
)	0
handling	0
proteins	0
.	0

The	0
expression	0
analysis	0
of	0
apoptosis	0
-	0
related	0
proteins	0
revealed	0
that	0
pro	0
-	0
apoptotic	0
protein	0
expression	0
was	0
upregulated	0
,	0
and	0
anti	0
-	0
apoptotic	0
protein	0
BCL	0
-	0
2	0
expression	0
was	0
downregulated	0
.	0

Furthermore	0
,	0
increased	0
phosphorylation	0
of	0
MAPK	0
family	0
members	0
,	0
especially	0
the	0
P	0
-	0
P38	0
/	0
P38	0
ratio	0
was	0
found	0
in	0
cardiac	0
tissues	0
.	0

Hence	0
,	0
our	0
results	0
suggest	0
that	0
aconitine	1
significantly	0
aggravates	0
Ca	1
(	0
2	0
+	0
)	0
overload	0
and	0
causes	0
arrhythmia	3
and	0
finally	0
promotes	0
apoptotic	0
development	0
via	0
phosphorylation	0
of	0
P38	0
mitogen	0
-	0
activated	0
protein	0
kinase	0
.	0

Chronic	0
treatment	0
with	0
metformin	1
suppresses	0
toll	0
-	0
like	0
receptor	0
4	0
signaling	0
and	0
attenuates	0
left	3
ventricular	4
dysfunction	4
following	0
myocardial	3
infarction	4
.	0

Acute	0
treatment	0
with	0
metformin	1
has	0
a	0
protective	0
effect	0
in	0
myocardial	3
infarction	4
by	0
suppression	0
of	0
inflammatory	0
responses	0
due	0
to	0
activation	0
of	0
AMP	1
-	0
activated	0
protein	0
kinase	0
(	0
AMPK	0
)	0
.	0

In	0
the	0
present	0
study	0
,	0
the	0
effect	0
of	0
chronic	0
pre	0
-	0
treatment	0
with	0
metformin	1
on	0
cardiac	3
dysfunction	4
and	0
toll	0
-	0
like	0
receptor	0
4	0
(	0
TLR4	0
)	0
activities	0
following	0
myocardial	3
infarction	4
and	0
their	0
relation	0
with	0
AMPK	0
were	0
assessed	0
.	0

Male	0
Wistar	0
rats	0
were	0
randomly	0
assigned	0
to	0
one	0
of	0
5	0
groups	0
(	0
n	0
=	0
6	0
)	0
:	0
normal	0
control	0
and	0
groups	0
were	0
injected	0
isoproterenol	1
after	0
chronic	0
pre	0
-	0
treatment	0
with	0
0	0
,	0
25	0
,	0
50	0
,	0
or	0
100mg	0
/	0
kg	0
of	0
metformin	1
twice	0
daily	0
for	0
14	0
days	0
.	0

Isoproterenol	1
(	0
100mg	0
/	0
kg	0
)	0
was	0
injected	0
subcutaneously	0
on	0
the	0
13th	0
and	0
14th	0
days	0
to	0
induce	0
acute	3
myocardial	4
infarction	4
.	0

Isoproterenol	1
alone	0
decreased	0
left	0
ventricular	0
systolic	0
pressure	0
and	0
myocardial	0
contractility	0
indexed	0
as	0
LVdp	0
/	0
dtmax	0
and	0
LVdp	0
/	0
dtmin	0
.	0

The	0
left	3
ventricular	4
dysfunction	4
was	0
significantly	0
lower	0
in	0
the	0
groups	0
treated	0
with	0
25	0
and	0
50mg	0
/	0
kg	0
of	0
metformin	1
.	0

Metfromin	0
markedly	0
lowered	0
isoproterenol	1
-	0
induced	0
elevation	0
in	0
the	0
levels	0
of	0
TLR4	0
mRNA	0
,	0
myeloid	0
differentiation	0
protein	0
88	0
(	0
MyD88	0
)	0
,	0
tumor	3
necrosis	3
factor	0
-	0
alpha	0
(	0
TNF	0
-	0
a	0
)	0
,	0
and	0
interleukin	0
6	0
(	0
IL	0
-	0
6	0
)	0
in	0
the	0
heart	0
tissues	0
.	0

Similar	0
changes	0
were	0
also	0
seen	0
in	0
the	0
serum	0
levels	0
of	0
TNF	0
-	0
a	0
and	0
IL	0
-	0
6	0
.	0

However	0
,	0
the	0
lower	0
doses	0
of	0
25	0
and	0
50mg	0
/	0
kg	0
were	0
more	0
effective	0
than	0
100mg	0
/	0
kg	0
.	0

Phosphorylated	0
AMPKa	0
(	0
p	0
-	0
AMPK	0
)	0
in	0
the	0
myocardium	0
was	0
significantly	0
elevated	0
by	0
25mg	0
/	0
kg	0
of	0
metformin	1
,	0
slightly	0
by	0
50mg	0
/	0
kg	0
,	0
but	0
not	0
by	0
100mg	0
/	0
kg	0
.	0

Chronic	0
pre	0
-	0
treatment	0
with	0
metformin	1
reduces	0
post	0
-	0
myocardial	3
infarction	4
cardiac	0
dysfunction	0
and	0
suppresses	0
inflammatory	0
responses	0
,	0
possibly	0
through	0
inhibition	0
of	0
TLR4	0
activities	0
.	0

This	0
mechanism	0
can	0
be	0
considered	0
as	0
a	0
target	0
to	0
protect	0
infarcted	0
myocardium	0
.	0

Unusual	0
complications	0
of	0
antithyroid	0
drug	0
therapy	0
:	0
four	0
case	0
reports	0
and	0
review	0
of	0
literature	0
.	0

Two	0
cases	0
of	0
propylthiouracil	1
-	0
associated	0
acute	0
hepatitis	3
,	0
one	0
case	0
of	0
fatal	0
methimazole	1
-	0
associated	0
hepatocellular	3
necrosis	4
and	0
one	0
case	0
of	0
propylthiouracil	1
-	0
associated	0
lupus	3
-	4
like	4
syndrome	4
are	0
described	0
.	0

The	0
literature	0
related	0
to	0
antithyroid	0
drug	0
side	0
effects	0
and	0
the	0
mechanisms	0
for	0
their	0
occurrence	0
are	0
reviewed	0
and	0
the	0
efficacy	0
and	0
complications	0
of	0
thyroidectomy	0
and	0
radioiodine	0
compared	0
to	0
those	0
of	0
antithyroid	0
drugs	0
.	0

It	0
is	0
concluded	0
that	0
in	0
most	0
circumstances	0
131I	0
is	0
the	0
therapy	0
of	0
choice	0
for	0
hyperthyroidism	3
.	0

Neuroleptic	3
malignant	4
syndrome	4
induced	0
by	0
combination	0
therapy	0
with	0
tetrabenazine	1
and	0
tiapride	1
in	0
a	0
Japanese	0
patient	0
with	0
Huntington	3
'	4
s	4
disease	4
at	0
the	0
terminal	0
stage	0
of	0
recurrent	0
breast	3
cancer	4
.	0

We	0
herein	0
describe	0
the	0
case	0
of	0
an	0
81	0
-	0
year	0
-	0
old	0
Japanese	0
woman	0
with	0
neuroleptic	3
malignant	4
syndrome	4
that	0
occurred	0
36	0
days	0
after	0
the	0
initiation	0
of	0
combination	0
therapy	0
with	0
tiapride	1
(	0
75	0
mg	0
/	0
day	0
)	0
and	0
tetrabenazine	1
(	0
12	0
.	0
5	0
mg	0
/	0
day	0
)	0
for	0
Huntington	3
'	4
s	4
disease	4
.	0

The	0
patient	0
had	0
been	0
treated	0
with	0
tiapride	1
or	0
tetrabenazine	1
alone	0
without	0
any	0
adverse	0
effects	0
before	0
the	0
administration	0
of	0
the	0
combination	0
therapy	0
.	0

She	0
also	0
had	0
advanced	0
breast	3
cancer	4
when	0
the	0
combination	0
therapy	0
was	0
initiated	0
.	0

To	0
the	0
best	0
of	0
our	0
knowledge	0
,	0
the	0
occurrence	0
of	0
neuroleptic	3
malignant	4
syndrome	4
due	0
to	0
combination	0
therapy	0
with	0
tetrabenazine	1
and	0
tiapride	1
has	0
not	0
been	0
previously	0
reported	0
.	0

Tetrabenazine	1
should	0
be	0
administered	0
very	0
carefully	0
in	0
combination	0
with	0
other	0
neuroleptic	1
drugs	2
,	0
particularly	0
in	0
patients	0
with	0
a	0
worsening	0
general	0
condition	0
.	0

A	0
metoprolol	1
-	0
terbinafine	1
combination	0
induced	0
bradycardia	3
.	0

To	0
report	0
a	0
sinus	3
bradycardia	4
induced	0
by	0
metoprolol	1
and	0
terbinafine	1
drug	0
-	0
drug	0
interaction	0
and	0
its	0
management	0
.	0

A	0
63	0
year	0
-	0
old	0
Caucasian	0
man	0
on	0
metoprolol	1
200	0
mg	0
/	0
day	0
for	0
stable	0
coronary	3
artery	4
disease	4
was	0
prescribed	0
a	0
90	0
-	0
day	0
course	0
of	0
oral	0
terbinafine	1
250	0
mg	0
/	0
day	0
for	0
onychomycosis	3
.	0

0n	0
the	0
49th	0
day	0
of	0
terbinafine	1
therapy	0
,	0
he	0
was	0
brought	0
to	0
the	0
emergency	0
room	0
for	0
a	0
decrease	0
of	0
his	0
global	0
health	0
status	0
,	0
confusion	3
and	0
falls	0
.	0

The	0
electrocardiogram	0
revealed	0
a	0
37	0
beats	0
/	0
min	0
sinus	3
bradycardia	4
.	0

A	0
score	0
of	0
7	0
on	0
the	0
Naranjo	0
adverse	3
drug	4
reaction	4
probability	0
scale	0
indicates	0
a	0
probable	0
relationship	0
between	0
the	0
patient	0
'	0
s	0
sinus	3
bradycardia	4
and	0
the	0
drug	0
interaction	0
between	0
metoprolol	1
and	0
terbinafine	1
.	0

The	0
heart	0
rate	0
ameliorated	0
first	0
with	0
a	0
decrease	0
in	0
the	0
dose	0
of	0
metoprolol	1
.	0

It	0
was	0
subsequently	0
changed	0
to	0
bisoprolol	1
and	0
the	0
heart	0
rate	0
remained	0
normal	0
.	0

By	0
inhibiting	0
the	0
cytochrome	0
P450	0
2D6	0
,	0
terbinafine	1
had	0
decreased	0
metoprolol	1
'	0
s	0
clearance	0
,	0
leading	0
in	0
metoprolol	1
accumulation	0
which	0
has	0
resulted	0
in	0
clinically	0
significant	0
sinus	3
bradycardia	4
.	0

0ptochiasmatic	0
and	0
peripheral	3
neuropathy	4
due	0
to	0
ethambutol	1
overtreatment	0
.	0

Ethambutol	1
is	0
known	0
to	0
cause	0
optic	3
neuropathy	4
and	0
,	0
more	0
rarely	0
,	0
axonal	0
polyneuropathy	3
.	0

We	0
characterize	0
the	0
clinical	0
,	0
neurophysiological	0
,	0
and	0
neuroimaging	0
findings	0
in	0
a	0
72	0
-	0
year	0
-	0
old	0
man	0
who	0
developed	0
visual	3
loss	4
and	0
paresthesias	3
after	0
11	0
weeks	0
of	0
exposure	0
to	0
a	0
supratherapeutic	0
dose	0
of	0
ethambutol	1
.	0

This	0
case	0
demonstrates	0
the	0
selective	0
vulnerability	0
of	0
the	0
anterior	0
visual	0
pathways	0
and	0
peripheral	0
nerves	0
to	0
ethambutol	1
toxicity	3
.	0

Testosterone	1
ameliorates	0
streptozotocin	1
-	0
induced	0
memory	3
impairment	4
in	0
male	0
rats	0
.	0

AIM	0
:	0
To	0
study	0
the	0
effects	0
of	0
testosterone	1
on	0
streptozotocin	1
(	0
STZ	1
)	0
-	0
induced	0
memory	3
impairment	4
in	0
male	0
rats	0
.	0

METH0DS	0
:	0
Adult	0
male	0
Wistar	0
rats	0
were	0
intracerebroventricularly	0
(	0
icv	0
)	0
infused	0
with	0
STZ	1
(	0
750	0
ug	0
)	0
on	0
d	0
1	0
and	0
d	0
3	0
,	0
and	0
a	0
passive	0
avoidance	0
task	0
was	0
assessed	0
2	0
weeks	0
after	0
the	0
first	0
injection	0
of	0
STZ	1
.	0

Castration	0
surgery	0
was	0
performed	0
in	0
another	0
group	0
of	0
rats	0
,	0
and	0
the	0
passive	0
avoidance	0
task	0
was	0
assessed	0
4	0
weeks	0
after	0
the	0
operation	0
.	0

Testosterone	1
(	0
1	0
mg	0
.	0
kg	0
(	0
-	0
1	0
)	0
.	0
d	0
(	0
-	0
1	0
)	0
,	0
sc	0
)	0
,	0
the	0
androgen	1
receptor	0
antagonist	0
flutamide	1
(	0
10	0
mg	0
.	0
kg	0
(	0
-	0
1	0
)	0
.	0
d	0
(	0
-	0
1	0
)	0
,	0
ip	0
)	0
,	0
the	0
estrogen	1
receptor	0
antagonist	0
tamoxifen	1
(	0
1	0
mg	0
.	0
kg	0
(	0
-	0
1	0
)	0
.	0
d	0
(	0
-	0
1	0
)	0
,	0
ip	0
)	0
or	0
the	0
aromatase	0
inhibitor	0
letrozole	1
(	0
4	0
mg	0
.	0
kg	0
(	0
-	0
1	0
)	0
.	0
d	0
(	0
-	0
1	0
)	0
,	0
ip	0
)	0
were	0
administered	0
for	0
6	0
d	0
after	0
the	0
first	0
injection	0
of	0
STZ	1
.	0

RESULTS	0
:	0
STZ	1
administration	0
and	0
castration	0
markedly	0
decreased	0
both	0
STL1	0
(	0
the	0
short	0
memory	0
)	0
and	0
STL2	0
(	0
the	0
long	0
memory	0
)	0
in	0
passive	0
avoidance	0
tests	0
.	0

Testosterone	1
replacement	0
almost	0
restored	0
the	0
STL1	0
and	0
STL2	0
in	0
castrated	0
rats	0
,	0
and	0
significantly	0
prolonged	0
the	0
STL1	0
and	0
STL2	0
in	0
STZ	1
-	0
treated	0
rats	0
.	0

Administration	0
of	0
flutamide	1
,	0
letrozole	1
or	0
tamoxifen	1
significantly	0
impaired	3
the	4
memory	4
in	0
intact	0
rats	0
,	0
and	0
significantly	0
attenuated	0
the	0
testosterone	1
replacement	0
in	0
improving	0
STZ	1
-	0
and	0
castration	0
-	0
induced	0
memory	3
impairment	4
.	0

C0NCLUSI0N	0
:	0
Testosterone	1
administration	0
ameliorates	0
STZ	1
-	0
and	0
castration	0
-	0
induced	0
memory	3
impairment	4
in	0
male	0
Wistar	0
rats	0
.	0

Behavioral	0
and	0
neurochemical	0
studies	0
in	0
mice	0
pretreated	0
with	0
garcinielliptone	1
FC	2
in	0
pilocarpine	1
-	0
induced	0
seizures	3
.	0

Garcinielliptone	1
FC	2
(	0
GFC	1
)	0
isolated	0
from	0
hexanic	0
fraction	0
seed	0
extract	0
of	0
species	0
Platonia	0
insignis	0
Mart	0
.	0

It	0
is	0
widely	0
used	0
in	0
folk	0
medicine	0
to	0
treat	0
skin	3
diseases	4
in	0
both	0
humans	0
and	0
animals	0
as	0
well	0
as	0
the	0
seed	0
decoction	0
has	0
been	0
used	0
to	0
treat	0
diarrheas	3
and	0
inflammatory	3
diseases	4
.	0

However	0
,	0
there	0
is	0
no	0
research	0
on	0
GFC	1
effects	0
in	0
the	0
central	0
nervous	0
system	0
of	0
rodents	0
.	0

The	0
present	0
study	0
aimed	0
to	0
evaluate	0
the	0
GFC	1
effects	0
at	0
doses	0
of	0
25	0
,	0
50	0
or	0
75	0
mg	0
/	0
kg	0
on	0
seizure	3
parameters	0
to	0
determine	0
their	0
anticonvulsant	0
activity	0
and	0
its	0
effects	0
on	0
amino	1
acid	2
(	0
r	1
-	2
aminobutyric	2
acid	2
(	0
GABA	1
)	0
,	0
glutamine	1
,	0
aspartate	1
and	0
glutathione	1
)	0
levels	0
as	0
well	0
as	0
on	0
acetylcholinesterase	0
(	0
AChE	0
)	0
activity	0
in	0
mice	0
hippocampus	0
after	0
seizures	3
.	0

GFC	1
produced	0
an	0
increased	0
latency	0
to	0
first	0
seizure	3
,	0
at	0
doses	0
25mg	0
/	0
kg	0
(	0
20	0
.	0
12	0
+	0
2	0
.	0
20	0
min	0
)	0
,	0
50mg	0
/	0
kg	0
(	0
20	0
.	0
95	0
+	0
2	0
.	0
21	0
min	0
)	0
or	0
75	0
mg	0
/	0
kg	0
(	0
23	0
.	0
43	0
+	0
1	0
.	0
99	0
min	0
)	0
when	0
compared	0
with	0
seized	0
mice	0
.	0

In	0
addition	0
,	0
GABA	1
content	0
of	0
mice	0
hippocampus	0
treated	0
with	0
GFC75	0
plus	0
P400	0
showed	0
an	0
increase	0
of	0
46	0
.	0
90	0
%	0
when	0
compared	0
with	0
seized	0
mice	0
.	0

In	0
aspartate	1
,	0
glutamine	1
and	0
glutamate	1
levels	0
detected	0
a	0
decrease	0
of	0
5	0
.	0
21	0
%	0
,	0
13	0
.	0
55	0
%	0
and	0
21	0
.	0
80	0
%	0
,	0
respectively	0
in	0
mice	0
hippocampus	0
treated	0
with	0
GFC75	0
plus	0
P400	0
when	0
compared	0
with	0
seized	0
mice	0
.	0

Hippocampus	0
mice	0
treated	0
with	0
GFC75	0
plus	0
P400	0
showed	0
an	0
increase	0
in	0
AChE	0
activity	0
(	0
63	0
.	0
30	0
%	0
)	0
when	0
compared	0
with	0
seized	0
mice	0
.	0

The	0
results	0
indicate	0
that	0
GFC	1
can	0
exert	0
anticonvulsant	0
activity	0
and	0
reduce	0
the	0
frequency	0
of	0
installation	0
of	0
pilocarpine	1
-	0
induced	0
status	3
epilepticus	4
,	0
as	0
demonstrated	0
by	0
increase	0
in	0
latency	0
to	0
first	0
seizure	3
and	0
decrease	0
in	0
mortality	0
rate	0
of	0
animals	0
.	0

In	0
conclusion	0
,	0
our	0
data	0
suggest	0
that	0
GFC	1
may	0
influence	0
in	0
epileptogenesis	0
and	0
promote	0
anticonvulsant	0
actions	0
in	0
pilocarpine	1
model	0
by	0
modulating	0
the	0
GABA	1
and	0
glutamate	1
contents	0
and	0
of	0
AChE	0
activity	0
in	0
seized	0
mice	0
hippocampus	0
.	0

This	0
compound	0
may	0
be	0
useful	0
to	0
produce	0
neuronal	0
protection	0
and	0
it	0
can	0
be	0
considered	0
as	0
an	0
anticonvulsant	0
agent	0
.	0

Standard	0
operating	0
procedures	0
for	0
antibiotic	0
therapy	0
and	0
the	0
occurrence	0
of	0
acute	3
kidney	4
injury	4
:	0
a	0
prospective	0
,	0
clinical	0
,	0
non	0
-	0
interventional	0
,	0
observational	0
study	0
.	0

INTR0DUCTI0N	0
:	0
Acute	3
kidney	4
injury	4
(	0
AKI	3
)	0
occurs	0
in	0
7	0
%	0
of	0
hospitalized	0
and	0
66	0
%	0
of	0
Intensive	0
Care	0
Unit	0
(	0
ICU	0
)	0
patients	0
.	0

It	0
increases	0
mortality	0
,	0
hospital	0
length	0
of	0
stay	0
,	0
and	0
costs	0
.	0

The	0
aim	0
of	0
this	0
study	0
was	0
to	0
investigate	0
,	0
whether	0
there	0
is	0
an	0
association	0
between	0
adherence	0
to	0
guidelines	0
(	0
standard	0
operating	0
procedures	0
(	0
S0P	0
)	0
)	0
for	0
potentially	0
nephrotoxic	3
antibiotics	0
and	0
the	0
occurrence	0
of	0
AKI	3
.	0

METH0DS	0
:	0
This	0
study	0
was	0
carried	0
out	0
as	0
a	0
prospective	0
,	0
clinical	0
,	0
non	0
-	0
interventional	0
,	0
observational	0
study	0
.	0

Data	0
collection	0
was	0
performed	0
over	0
a	0
total	0
of	0
170	0
days	0
in	0
three	0
ICUs	0
at	0
Charite	0
-	0
Universitaetsmedizin	0
Berlin	0
.	0

A	0
total	0
of	0
675	0
patients	0
were	0
included	0
;	0
163	0
of	0
these	0
had	0
therapy	0
with	0
vancomycin	1
,	0
gentamicin	1
,	0
or	0
tobramycin	1
;	0
were	0
>	0
18	0
years	0
;	0
and	0
treated	0
in	0
the	0
ICU	0
for	0
>	0
24	0
hours	0
.	0

Patients	0
with	0
an	0
adherence	0
to	0
S0P	0
>	0
70	0
%	0
were	0
classified	0
into	0
the	0
high	0
adherence	0
group	0
(	0
HAG	0
)	0
and	0
patients	0
with	0
an	0
adherence	0
of	0
<	0
70	0
%	0
into	0
the	0
low	0
adherence	0
group	0
(	0
LAG	0
)	0
.	0

AKI	3
was	0
defined	0
according	0
to	0
RIFLE	0
criteria	0
.	0

Adherence	0
to	0
S0Ps	0
was	0
evaluated	0
by	0
retrospective	0
expert	0
audit	0
.	0

Development	0
of	0
AKI	3
was	0
compared	0
between	0
groups	0
with	0
exact	0
Chi2	0
-	0
test	0
and	0
multivariate	0
logistic	0
regression	0
analysis	0
(	0
two	0
-	0
sided	0
P	0
<	0
0	0
.	0
05	0
)	0
.	0

RESULTS	0
:	0
LAG	0
consisted	0
of	0
75	0
patients	0
(	0
46	0
%	0
)	0
versus	0
88	0
HAG	0
patients	0
(	0
54	0
%	0
)	0
.	0

AKI	3
occurred	0
significantly	0
more	0
often	0
in	0
LAG	0
with	0
36	0
%	0
versus	0
21	0
%	0
in	0
HAG	0
(	0
P	0
=	0
0	0
.	0
035	0
)	0
.	0

Basic	0
characteristics	0
were	0
comparable	0
,	0
except	0
an	0
increased	0
rate	0
of	0
soft	0
tissue	0
infections	3
in	0
LAG	0
.	0

Multivariate	0
analysis	0
revealed	0
an	0
odds	0
ratio	0
of	0
2	0
.	0
5	0
-	0
fold	0
for	0
LAG	0
to	0
develop	0
AKI	3
compared	0
with	0
HAG	0
(	0
95	0
%	0
confidence	0
interval	0
1	0
.	0
195	0
to	0
5	0
.	0
124	0
,	0
P	0
=	0
0	0
.	0
039	0
)	0
.	0

C0NCLUSI0N	0
:	0
Low	0
adherence	0
to	0
S0Ps	0
for	0
potentially	0
nephrotoxic	3
antibiotics	0
was	0
associated	0
with	0
a	0
higher	0
occurrence	0
of	0
AKI	3
.	0

TRIAL	0
REGISTRATI0N	0
:	0
Current	0
Controlled	0
Trials	0
ISRCTN54598675	0
.	0

Registered	0
17	0
August	0
2007	0
.	0

Rhabdomyolysis	3
in	0
a	0
hepatitis	3
C	4
virus	4
infected	4
patient	0
treated	0
with	0
telaprevir	1
and	0
simvastatin	1
.	0

A	0
46	0
-	0
year	0
old	0
man	0
with	0
a	0
chronic	0
hepatitis	3
C	4
virus	4
infection	4
received	0
triple	0
therapy	0
with	0
ribavirin	1
,	0
pegylated	1
interferon	2
and	0
telaprevir	1
.	0

The	0
patient	0
also	0
received	0
simvastatin	1
.	0

0ne	0
month	0
after	0
starting	0
the	0
antiviral	0
therapy	0
,	0
the	0
patient	0
was	0
admitted	0
to	0
the	0
hospital	0
because	0
he	0
developed	0
rhabdomyolysis	3
.	0

At	0
admission	0
simvastatin	1
and	0
all	0
antiviral	0
drugs	0
were	0
discontinued	0
because	0
toxicity	3
due	0
to	0
a	0
drug	0
-	0
drug	0
interaction	0
was	0
suspected	0
.	0

The	0
creatine	1
kinase	0
peaked	0
at	0
62	0
,	0
246	0
IU	0
/	0
L	0
and	0
the	0
patient	0
was	0
treated	0
with	0
intravenous	0
normal	0
saline	0
.	0

The	0
patient	0
'	0
s	0
renal	0
function	0
remained	0
unaffected	0
.	0

Fourteen	0
days	0
after	0
hospitalization	0
,	0
creatine	1
kinase	0
level	0
had	0
returned	0
to	0
230	0
IU	0
/	0
L	0
and	0
the	0
patient	0
was	0
discharged	0
.	0

Telaprevir	1
was	0
considered	0
the	0
probable	0
causative	0
agent	0
of	0
an	0
interaction	0
with	0
simvastatin	1
according	0
to	0
the	0
Drug	0
Interaction	0
Probability	0
Scale	0
.	0

The	0
interaction	0
is	0
due	0
to	0
inhibition	0
of	0
CYP3A4	0
-	0
mediated	0
simvastatin	1
clearance	0
.	0

Simvastatin	1
plasma	0
concentration	0
increased	0
30	0
times	0
in	0
this	0
patient	0
and	0
statin	1
induced	0
muscle	3
toxicity	4
is	0
related	0
to	0
the	0
concentration	0
of	0
the	0
statin	1
in	0
blood	0
.	0

In	0
conclusion	0
,	0
with	0
this	0
case	0
we	0
illustrate	0
that	0
telaprevir	1
as	0
well	0
as	0
statins	1
are	0
susceptible	0
to	0
clinical	0
relevant	0
drug	0
-	0
drug	0
interactions	0
.	0

Combination	0
of	0
bortezomib	1
,	0
thalidomide	1
,	0
and	0
dexamethasone	1
(	0
VTD	0
)	0
as	0
a	0
consolidation	0
therapy	0
after	0
autologous	0
stem	0
cell	0
transplantation	0
for	0
symptomatic	0
multiple	3
myeloma	4
in	0
Japanese	0
patients	0
.	0

Consolidation	0
therapy	0
for	0
patients	0
with	0
multiple	3
myeloma	4
(	0
MM	3
)	0
has	0
been	0
widely	0
adopted	0
to	0
improve	0
treatment	0
response	0
following	0
autologous	0
stem	0
cell	0
transplantation	0
.	0

In	0
this	0
study	0
,	0
we	0
retrospectively	0
analyzed	0
the	0
safety	0
and	0
efficacy	0
of	0
combination	0
regimen	0
of	0
bortezomib	1
,	0
thalidomide	1
,	0
and	0
dexamethasone	1
(	0
VTD	0
)	0
as	0
consolidation	0
therapy	0
in	0
24	0
Japanese	0
patients	0
with	0
newly	0
diagnosed	0
MM	3
.	0

VTD	0
consisted	0
of	0
bortezomib	1
at	0
a	0
dose	0
of	0
1	0
.	0
3	0
mg	0
/	0
m	0
(	0
2	0
)	0
and	0
dexamethasone	1
at	0
a	0
dose	0
of	0
40	0
mg	0
/	0
day	0
on	0
days	0
1	0
,	0
8	0
,	0
15	0
,	0
and	0
22	0
of	0
a	0
35	0
-	0
day	0
cycle	0
,	0
with	0
daily	0
oral	0
thalidomide	1
at	0
a	0
dose	0
of	0
100	0
mg	0
/	0
day	0
.	0

Grade	0
3	0
-	0
4	0
neutropenia	3
and	0
thrombocytopenia	3
were	0
documented	0
in	0
four	0
and	0
three	0
patients	0
(	0
17	0
and	0
13	0
%	0
)	0
,	0
respectively	0
,	0
but	0
drug	0
dose	0
reduction	0
due	0
to	0
cytopenia	3
was	0
not	0
required	0
in	0
any	0
case	0
.	0

Peripheral	3
neuropathy	4
was	0
common	0
(	0
63	0
%	0
)	0
,	0
but	0
severe	0
grade	0
3	0
-	0
4	0
peripheral	3
neuropathy	4
was	0
not	0
observed	0
.	0

Very	0
good	0
partial	0
response	0
or	0
better	0
response	0
(	0
>	0
VGPR	0
)	0
rates	0
before	0
and	0
after	0
consolidation	0
therapy	0
were	0
54	0
and	0
79	0
%	0
,	0
respectively	0
.	0

Patients	0
had	0
a	0
significant	0
probability	0
of	0
improving	0
from	0
<	0
VGPR	0
before	0
consolidation	0
therapy	0
to	0
>	0
VGPR	0
after	0
consolidation	0
therapy	0
(	0
p	0
=	0
0	0
.	0
041	0
)	0
.	0

The	0
VTD	0
regimen	0
may	0
be	0
safe	0
and	0
effective	0
as	0
a	0
consolidation	0
therapy	0
in	0
the	0
treatment	0
of	0
MM	0
in	0
Japanese	0
population	0
.	0

Conversion	0
to	0
sirolimus	1
ameliorates	0
cyclosporine	1
-	0
induced	0
nephropathy	3
in	0
the	0
rat	0
:	0
focus	0
on	0
serum	0
,	0
urine	0
,	0
gene	0
,	0
and	0
protein	0
renal	0
expression	0
biomarkers	0
.	0

Protocols	0
of	0
conversion	0
from	0
cyclosporin	1
A	2
(	0
CsA	1
)	0
to	0
sirolimus	1
(	0
SRL	1
)	0
have	0
been	0
widely	0
used	0
in	0
immunotherapy	0
after	0
transplantation	0
to	0
prevent	0
CsA	1
-	0
induced	0
nephropathy	3
,	0
but	0
the	0
molecular	0
mechanisms	0
underlying	0
these	0
protocols	0
remain	0
nuclear	0
.	0

This	0
study	0
aimed	0
to	0
identify	0
the	0
molecular	0
pathways	0
and	0
putative	0
biomarkers	0
of	0
CsA	1
-	0
to	0
-	0
SRL	1
conversion	0
in	0
a	0
rat	0
model	0
.	0

Four	0
animal	0
groups	0
(	0
n	0
=	0
6	0
)	0
were	0
tested	0
during	0
9	0
weeks	0
:	0
control	0
,	0
CsA	1
,	0
SRL	1
,	0
and	0
conversion	0
(	0
CsA	1
for	0
3	0
weeks	0
followed	0
by	0
SRL	1
for	0
6	0
weeks	0
)	0
.	0

Classical	0
and	0
emergent	0
serum	0
,	0
urinary	0
,	0
and	0
kidney	0
tissue	0
(	0
gene	0
and	0
protein	0
expression	0
)	0
markers	0
were	0
assessed	0
.	0

Renal	3
lesions	4
were	0
analyzed	0
in	0
hematoxylin	1
and	0
eosin	1
,	0
periodic	0
acid	0
-	0
Schiff	0
,	0
and	0
Masson	0
'	0
s	0
trichrome	0
stains	0
.	0

SRL	1
-	0
treated	0
rats	0
presented	0
proteinuria	3
and	0
NGAL	0
(	0
serum	0
and	0
urinary	0
)	0
as	0
the	0
best	0
markers	0
of	0
renal	3
impairment	4
.	0

Short	0
CsA	1
treatment	0
presented	0
slight	0
or	0
even	0
absent	0
kidney	3
lesions	4
and	0
TGF	0
-	0
b	0
,	0
NF	0
-	0
kb	0
,	0
mT0R	0
,	0
PCNA	0
,	0
TP53	0
,	0
KIM	0
-	0
1	0
,	0
and	0
CTGF	0
as	0
relevant	0
gene	0
and	0
protein	0
changes	0
.	0

Prolonged	0
CsA	1
exposure	0
aggravated	0
renal	3
damage	4
,	0
without	0
clear	0
changes	0
on	0
the	0
traditional	0
markers	0
,	0
but	0
with	0
changes	0
in	0
serums	0
TGF	0
-	0
b	0
and	0
IL	0
-	0
7	0
,	0
TBARs	0
clearance	0
,	0
and	0
kidney	0
TGF	0
-	0
b	0
and	0
mT0R	0
.	0

Conversion	0
to	0
SRL	1
prevented	0
CsA	1
-	0
induced	0
renal	3
damage	4
evolution	0
(	0
absent	0
/	0
mild	0
grade	0
lesions	0
)	0
,	0
while	0
NGAL	0
(	0
serum	0
versus	0
urine	0
)	0
seems	0
to	0
be	0
a	0
feasible	0
biomarker	0
of	0
CsA	1
replacement	0
to	0
SRL	1
.	0

Kinin	0
B2	0
receptor	0
deletion	0
and	0
blockage	0
ameliorates	0
cisplatin	1
-	0
induced	0
acute	3
renal	4
injury	4
.	0

Cisplatin	1
treatment	0
has	0
been	0
adopted	0
in	0
some	0
chemotherapies	0
;	0
however	0
,	0
this	0
drug	0
can	0
induce	0
acute	3
kidney	4
injury	4
due	0
its	0
ability	0
to	0
negatively	0
affect	0
renal	0
function	0
,	0
augment	0
serum	0
levels	0
of	0
creatinine	1
and	0
urea	1
,	0
increase	0
the	0
acute	3
tubular	4
necrosis	4
score	0
and	0
up	0
-	0
regulate	0
cytokines	0
(	0
e	0
.	0
g	0
.	0
,	0
IL	0
-	0
1b	0
and	0
TNF	0
-	0
a	0
)	0
.	0

The	0
kinin	0
B2	0
receptor	0
has	0
been	0
associated	0
with	0
the	0
inflammation	3
process	0
,	0
as	0
well	0
as	0
the	0
regulation	0
of	0
cytokine	0
expression	0
,	0
and	0
its	0
deletion	0
resulted	0
in	0
an	0
improvement	0
in	0
the	0
diabetic	3
nephropathy	4
status	0
.	0

To	0
examine	0
the	0
role	0
of	0
the	0
kinin	0
B2	0
receptor	0
in	0
cisplatin	1
-	0
induced	0
acute	3
kidney	4
injury	4
,	0
kinin	0
B2	0
receptor	0
knockout	0
mice	0
were	0
challenged	0
with	0
cisplatin	1
.	0

Additionally	0
,	0
WT	0
mice	0
were	0
treated	0
with	0
a	0
B2	0
receptor	0
antagonist	0
after	0
cisplatin	1
administration	0
.	0

B2	0
receptor	0
-	0
deficient	0
mice	0
were	0
less	0
sensitive	0
to	0
this	0
drug	0
than	0
the	0
WT	0
mice	0
,	0
as	0
shown	0
by	0
reduced	0
weight	3
loss	4
,	0
better	0
preservation	0
of	0
kidney	0
function	0
,	0
down	0
regulation	0
of	0
inflammatory	0
cytokines	0
and	0
less	0
acute	3
tubular	4
necrosis	4
.	0

Moreover	0
,	0
treatment	0
with	0
the	0
kinin	0
B2	0
receptor	0
antagonist	0
effectively	0
reduced	0
the	0
levels	0
of	0
serum	0
creatinine	1
and	0
blood	0
urea	1
after	0
cisplatin	1
administration	0
.	0

Thus	0
,	0
our	0
data	0
suggest	0
that	0
the	0
kinin	0
B2	0
receptor	0
is	0
involved	0
in	0
cisplatin	1
-	0
induced	0
acute	3
kidney	4
injury	4
by	0
mediating	0
the	0
necrotic	3
process	0
and	0
the	0
expression	0
of	0
inflammatory	0
cytokines	0
,	0
thus	0
resulting	0
in	0
declined	0
renal	0
function	0
.	0

These	0
results	0
highlight	0
the	0
kinin	0
B2	0
receptor	0
antagonist	0
treatment	0
in	0
amelioration	0
of	0
nephrotoxicity	3
induced	0
by	0
cisplatin	1
therapy	0
.	0

Safety	0
and	0
efficacy	0
of	0
fluocinolone	1
acetonide	2
intravitreal	0
implant	0
(	0
0	0
.	0
59	0
mg	0
)	0
in	0
birdshot	3
retinochoroidopathy	4
.	0

PURP0SE	0
:	0
To	0
report	0
the	0
treatment	0
outcomes	0
of	0
the	0
fluocinolone	1
acetonide	2
intravitreal	0
implant	0
(	0
0	0
.	0
59	0
mg	0
)	0
in	0
patients	0
with	0
birdshot	3
retinochoroidopathy	4
whose	0
disease	0
is	0
refractory	0
or	0
intolerant	0
to	0
conventional	0
immunomodulatory	0
therapy	0
.	0

METH0DS	0
:	0
A	0
retrospective	0
case	0
series	0
involving	0
11	0
birdshot	3
retinochoroidopathy	4
patients	0
(	0
11	0
eyes	0
)	0
.	0

Eleven	0
patients	0
(	0
11	0
eyes	0
)	0
underwent	0
surgery	0
for	0
fluocinolone	1
acetonide	2
implant	0
(	0
0	0
.	0
59	0
mg	0
)	0
.	0

Treatment	0
outcomes	0
of	0
interest	0
were	0
noted	0
at	0
baseline	0
,	0
before	0
fluocinolone	1
acetonide	2
implant	0
,	0
and	0
then	0
at	0
6	0
months	0
,	0
1	0
year	0
,	0
2	0
years	0
,	0
3	0
years	0
,	0
and	0
beyond	0
3	0
years	0
.	0

Disease	0
activity	0
markers	0
,	0
including	0
signs	0
of	0
ocular	0
inflammation	3
,	0
evidence	0
of	0
retinal	3
vasculitis	4
,	0
Swedish	0
interactive	0
threshold	0
algorithm	0
-	0
short	0
wavelength	0
automated	0
perimetry	0
Humphrey	0
visual	0
field	0
analysis	0
,	0
electroretinographic	0
parameters	0
,	0
and	0
optical	0
coherence	0
tomography	0
were	0
recorded	0
.	0

Data	0
on	0
occurrence	0
of	0
cataract	3
and	0
raised	3
intraocular	4
pressure	4
were	0
collected	0
in	0
all	0
eyes	0
.	0

RESULTS	0
:	0
Intraocular	0
inflammation	3
was	0
present	0
in	0
54	0
.	0
5	0
,	0
9	0
.	0
9	0
,	0
11	0
.	0
1	0
,	0
and	0
0	0
%	0
of	0
patients	0
at	0
baseline	0
,	0
6	0
months	0
,	0
1	0
year	0
,	0
2	0
years	0
,	0
3	0
years	0
,	0
and	0
beyond	0
3	0
years	0
after	0
receiving	0
the	0
implant	0
,	0
respectively	0
.	0

Active	0
vasculitis	3
was	0
noted	0
in	0
36	0
.	0
3	0
%	0
patients	0
at	0
baseline	0
and	0
0	0
%	0
at	0
3	0
years	0
of	0
follow	0
-	0
up	0
.	0

More	0
than	0
20	0
%	0
(	0
47	0
.	0
61	0
-	0
67	0
.	0
2	0
%	0
)	0
reduction	0
in	0
central	0
retinal	0
thickness	0
was	0
noted	0
in	0
all	0
patients	0
with	0
cystoid	3
macular	4
edema	4
at	0
6	0
months	0
,	0
1	0
year	0
,	0
2	0
years	0
,	0
and	0
3	0
years	0
postimplant	0
.	0

At	0
baseline	0
,	0
54	0
.	0
5	0
%	0
patients	0
were	0
on	0
immunomodulatory	0
agents	0
.	0

This	0
percentage	0
decreased	0
to	0
45	0
.	0
45	0
,	0
44	0
.	0
4	0
,	0
and	0
14	0
.	0
28	0
%	0
at	0
1	0
year	0
,	0
2	0
years	0
,	0
and	0
3	0
years	0
postimplant	0
,	0
respectively	0
.	0

Adverse	0
events	0
included	0
increased	3
intraocular	4
pressure	4
(	0
54	0
.	0
5	0
%	0
)	0
and	0
cataract	3
formation	0
(	0
100	0
%	0
)	0
.	0

C0NCLUSI0N	0
:	0
The	0
data	0
suggest	0
that	0
fluocinolone	1
acetonide	2
implant	0
(	0
0	0
.	0
59	0
mg	0
)	0
helps	0
to	0
control	0
inflammation	3
in	0
otherwise	0
treatment	0
-	0
refractory	0
cases	0
of	0
birdshot	3
retinochoroidopathy	4
.	0

It	0
is	0
associated	0
with	0
significant	0
side	0
effects	0
of	0
cataract	3
and	0
ocular	3
hypertension	4
requiring	0
treatment	0
.	0

0ptimal	0
precurarizing	0
dose	0
of	0
rocuronium	1
to	0
decrease	0
fasciculation	3
and	0
myalgia	3
following	0
succinylcholine	1
administration	0
.	0

BACKGR0UND	0
:	0
Succinylcholine	1
commonly	0
produces	0
frequent	0
adverse	0
effects	0
,	0
including	0
muscle	3
fasciculation	4
and	0
myalgia	3
.	0

The	0
current	0
study	0
identified	0
the	0
optimal	0
dose	0
of	0
rocuronium	1
to	0
prevent	0
succinylcholine	1
-	0
induced	0
fasciculation	3
and	0
myalgia	3
and	0
evaluated	0
the	0
influence	0
of	0
rocuronium	1
on	0
the	0
speed	0
of	0
onset	0
produced	0
by	0
succinylcholine	1
.	0

METH0DS	0
:	0
This	0
randomized	0
,	0
double	0
-	0
blinded	0
study	0
was	0
conducted	0
in	0
100	0
patients	0
randomly	0
allocated	0
into	0
five	0
groups	0
of	0
20	0
patients	0
each	0
.	0

Patients	0
were	0
randomized	0
to	0
receive	0
0	0
.	0
02	0
,	0
0	0
.	0
03	0
,	0
0	0
.	0
04	0
,	0
0	0
.	0
05	0
and	0
0	0
.	0
06	0
mg	0
/	0
kg	0
rocuronium	1
as	0
a	0
precurarizing	0
dose	0
.	0

Neuromuscular	0
monitoring	0
after	0
each	0
precurarizing	0
dose	0
was	0
recorded	0
from	0
the	0
adductor	0
pollicis	0
muscle	0
using	0
acceleromyography	0
with	0
train	0
-	0
of	0
-	0
four	0
stimulation	0
of	0
the	0
ulnar	0
nerve	0
.	0

All	0
patients	0
received	0
succinylcholine	1
1	0
.	0
5	0
mg	0
/	0
kg	0
at	0
2	0
minutes	0
after	0
the	0
precurarization	0
,	0
and	0
were	0
assessed	0
the	0
incidence	0
and	0
severity	0
of	0
fasciculations	3
,	0
while	0
myalgia	3
was	0
assessed	0
at	0
24	0
hours	0
after	0
surgery	0
.	0

RESULTS	0
:	0
The	0
incidence	0
and	0
severity	0
of	0
visible	0
muscle	3
fasciculation	4
was	0
significantly	0
less	0
with	0
increasing	0
the	0
amount	0
of	0
precurarizing	0
dose	0
of	0
rocuronium	1
(	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

Those	0
of	0
myalgia	3
tend	0
to	0
decrease	0
according	0
to	0
increasing	0
the	0
amount	0
of	0
precurarizing	0
dose	0
of	0
rocuronium	1
,	0
but	0
there	0
was	0
no	0
significance	0
(	0
P	0
=	0
0	0
.	0
072	0
)	0
.	0

The	0
onset	0
time	0
of	0
succinylcholine	1
was	0
significantly	0
longer	0
with	0
increasing	0
the	0
amount	0
of	0
precurarizing	0
dose	0
of	0
rocuronium	1
(	0
P	0
<	0
0	0
.	0
001	0
)	0
.	0

C0NCLUSI0NS	0
:	0
Precurarization	0
with	0
0	0
.	0
04	0
mg	0
/	0
kg	0
rocuronium	1
was	0
the	0
optimal	0
dose	0
considering	0
the	0
reduction	0
in	0
the	0
incidence	0
and	0
severity	0
of	0
fasciculation	3
and	0
myalgia	3
with	0
acceptable	0
onset	0
time	0
,	0
and	0
the	0
safe	0
and	0
effective	0
precurarization	0
.	0

Absence	0
of	0
PKC	0
-	0
alpha	0
attenuates	0
lithium	1
-	0
induced	0
nephrogenic	3
diabetes	4
insipidus	4
.	0

Lithium	1
,	0
an	0
effective	0
antipsychotic	0
,	0
induces	0
nephrogenic	3
diabetes	4
insipidus	4
(	0
NDI	3
)	0
in	0
40	0
%	0
of	0
patients	0
.	0

The	0
decreased	0
capacity	0
to	0
concentrate	0
urine	0
is	0
likely	0
due	0
to	0
lithium	1
acutely	0
disrupting	0
the	0
cAMP	1
pathway	0
and	0
chronically	0
reducing	0
urea	1
transporter	0
(	0
UT	0
-	0
A1	0
)	0
and	0
water	0
channel	0
(	0
AQP2	0
)	0
expression	0
in	0
the	0
inner	0
medulla	0
.	0

Targeting	0
an	0
alternative	0
signaling	0
pathway	0
,	0
such	0
as	0
PKC	0
-	0
mediated	0
signaling	0
,	0
may	0
be	0
an	0
effective	0
method	0
of	0
treating	0
lithium	1
-	0
induced	0
polyuria	3
.	0

PKC	0
-	0
alpha	0
null	0
mice	0
(	0
PKCa	0
K0	0
)	0
and	0
strain	0
-	0
matched	0
wild	0
type	0
(	0
WT	0
)	0
controls	0
were	0
treated	0
with	0
lithium	1
for	0
0	0
,	0
3	0
or	0
5	0
days	0
.	0

WT	0
mice	0
had	0
increased	0
urine	0
output	0
and	0
lowered	0
urine	0
osmolality	0
after	0
3	0
and	0
5	0
days	0
of	0
treatment	0
whereas	0
PKCa	0
K0	0
mice	0
had	0
no	0
change	0
in	0
urine	0
output	0
or	0
concentration	0
.	0

Western	0
blot	0
analysis	0
revealed	0
that	0
AQP2	0
expression	0
in	0
medullary	0
tissues	0
was	0
lowered	0
after	0
3	0
and	0
5	0
days	0
in	0
WT	0
mice	0
;	0
however	0
,	0
AQP2	0
was	0
unchanged	0
in	0
PKCa	0
K0	0
.	0

Similar	0
results	0
were	0
observed	0
with	0
UT	0
-	0
A1	0
expression	0
.	0

Animals	0
were	0
also	0
treated	0
with	0
lithium	1
for	0
6	0
weeks	0
.	0

Lithium	1
-	0
treated	0
WT	0
mice	0
had	0
19	0
-	0
fold	0
increased	0
urine	0
output	0
whereas	0
treated	0
PKCa	0
K0	0
animals	0
had	0
a	0
4	0
-	0
fold	0
increase	0
in	0
output	0
.	0

AQP2	0
and	0
UT	0
-	0
A1	0
expression	0
was	0
lowered	0
in	0
6	0
week	0
lithium	1
-	0
treated	0
WT	0
animals	0
whereas	0
in	0
treated	0
PKCa	0
K0	0
mice	0
,	0
AQP2	0
was	0
only	0
reduced	0
by	0
2	0
-	0
fold	0
and	0
UT	0
-	0
A1	0
expression	0
was	0
unaffected	0
.	0

Urinary	0
sodium	1
,	0
potassium	1
and	0
calcium	1
were	0
elevated	0
in	0
lithium	1
-	0
fed	0
WT	0
but	0
not	0
in	0
lithium	1
-	0
fed	0
PKCa	0
K0	0
mice	0
.	0

0ur	0
data	0
show	0
that	0
ablation	0
of	0
PKCa	0
preserves	0
AQP2	0
and	0
UT	0
-	0
A1	0
protein	0
expression	0
and	0
localization	0
in	0
lithium	1
-	0
induced	0
NDI	3
,	0
and	0
prevents	0
the	0
development	0
of	0
the	0
severe	0
polyuria	3
associated	0
with	0
lithium	1
therapy	0
.	0

Is	0
Dysguesia	3
Going	0
to	0
be	0
a	0
Rare	0
or	0
a	0
Common	0
Side	0
-	0
effect	0
of	0
Amlodipine	1
?	0

A	0
very	0
rare	0
side	0
-	0
effect	0
of	0
amlodipine	1
is	0
dysguesia	3
.	0

A	0
review	0
of	0
the	0
literature	0
produced	0
only	0
one	0
case	0
.	0

We	0
report	0
a	0
case	0
about	0
a	0
female	0
with	0
essential	0
hypertension	3
on	0
drug	0
treatment	0
with	0
amlodipine	1
developed	0
loss	3
of	4
taste	4
sensation	4
.	0

Condition	0
moderately	0
improved	0
on	0
stoppage	0
of	0
the	0
drug	0
for	0
25	0
days	0
.	0

We	0
conclude	0
that	0
amlodipine	1
can	0
cause	0
dysguesia	3
.	0

Here	0
,	0
we	0
describe	0
the	0
clinical	0
presentation	0
and	0
review	0
the	0
relevant	0
literature	0
on	0
amlodipine	1
and	0
dysguesia	3
.	0

Rhabdomyolysis	3
in	0
association	0
with	0
simvastatin	1
and	0
dosage	0
increment	0
in	0
clarithromycin	1
.	0

Clarithromycin	1
is	0
the	0
most	0
documented	0
cytochrome	0
P450	0
3A4	0
(	0
CYP3A4	0
)	0
inhibitor	0
to	0
cause	0
an	0
adverse	0
interaction	0
with	0
simvastatin	1
.	0

This	0
particular	0
case	0
is	0
of	0
interest	0
as	0
rhabdomyolysis	3
only	0
occurred	0
after	0
an	0
increase	0
in	0
the	0
dose	0
of	0
clarithromycin	1
.	0

The	0
patient	0
developed	0
raised	0
cardiac	0
biomarkers	0
without	0
any	0
obvious	0
cardiac	0
issues	0
,	0
a	0
phenomenon	0
that	0
has	0
been	0
linked	0
to	0
rhabdomyolysis	3
previously	0
.	0

To	0
date	0
,	0
there	0
has	0
been	0
no	0
reported	0
effect	0
of	0
rhabdomyolysis	3
on	0
the	0
structure	0
and	0
function	0
of	0
cardiac	0
muscle	0
.	0

Clinicians	0
need	0
to	0
be	0
aware	0
of	0
prescribing	0
concomitant	0
medications	0
that	0
increase	0
the	0
risk	0
of	0
myopathy	3
or	0
inhibit	0
the	0
CYP3A4	0
enzyme	0
.	0

0ur	0
case	0
suggests	0
that	0
troponin	0
elevation	0
could	0
be	0
associated	0
with	0
statin	1
induced	0
rhabdomyolysis	3
,	0
which	0
may	0
warrant	0
further	0
studies	0
.	0

Characterization	0
of	0
a	0
novel	0
BCHE	0
"	0
silent	0
"	0
allele	0
:	0
point	0
mutation	0
(	0
p	0
.	0
Val204Asp	0
)	0
causes	0
loss	0
of	0
activity	0
and	0
prolonged	0
apnea	3
with	0
suxamethonium	1
.	0

Butyrylcholinesterase	3
deficiency	4
is	0
characterized	0
by	0
prolonged	0
apnea	3
after	0
the	0
use	0
of	0
muscle	0
relaxants	0
(	0
suxamethonium	1
or	0
mivacurium	1
)	0
in	0
patients	0
who	0
have	0
mutations	0
in	0
the	0
BCHE	0
gene	0
.	0

Here	0
,	0
we	0
report	0
a	0
case	0
of	0
prolonged	0
neuromuscular	0
block	0
after	0
administration	0
of	0
suxamethonium	1
leading	0
to	0
the	0
discovery	0
of	0
a	0
novel	0
BCHE	0
variant	0
(	0
c	0
.	0
695T	0
>	0
A	0
,	0
p	0
.	0
Val204Asp	0
)	0
.	0

Inhibition	0
studies	0
,	0
kinetic	0
analysis	0
and	0
molecular	0
dynamics	0
were	0
undertaken	0
to	0
understand	0
how	0
this	0
mutation	0
disrupts	0
the	0
catalytic	0
triad	0
and	0
determines	0
a	0
"	0
silent	0
"	0
phenotype	0
.	0

Low	0
activity	0
of	0
patient	0
plasma	0
butyrylcholinesterase	0
with	0
butyrylthiocholine	1
(	0
BTC	1
)	0
and	0
benzoylcholine	1
,	0
and	0
values	0
of	0
dibucaine	1
and	0
fluoride	1
numbers	0
fit	0
with	0
heterozygous	0
atypical	0
silent	0
genotype	0
.	0

Electrophoretic	0
analysis	0
of	0
plasma	0
BChE	0
of	0
the	0
proband	0
and	0
his	0
mother	0
showed	0
that	0
patient	0
has	0
a	0
reduced	0
amount	0
of	0
tetrameric	0
enzyme	0
in	0
plasma	0
and	0
that	0
minor	0
fast	0
-	0
moving	0
BChE	0
components	0
:	0
monomer	0
,	0
dimer	0
,	0
and	0
monomer	0
-	0
albumin	0
conjugate	0
are	0
missing	0
.	0

Kinetic	0
analysis	0
showed	0
that	0
the	0
p	0
.	0
Val204Asp	0
/	0
p	0
.	0
Asp70Gly	0
-	0
p	0
.	0
Ala539Thr	0
BChE	0
displays	0
a	0
pure	0
Michaelian	0
behavior	0
with	0
BTC	1
as	0
the	0
substrate	0
.	0

Both	0
catalytic	0
parameters	0
Km	0
=	0
265	0
uM	0
for	0
BTC	1
,	0
two	0
times	0
higher	0
than	0
that	0
of	0
the	0
atypical	0
enzyme	0
,	0
and	0
a	0
low	0
Vmax	0
are	0
consistent	0
with	0
the	0
absence	0
of	0
activity	0
against	0
suxamethonium	1
.	0

Molecular	0
dynamic	0
(	0
MD	0
)	0
simulations	0
showed	0
that	0
the	0
overall	0
effect	0
of	0
the	0
mutation	0
p	0
.	0
Val204Asp	0
is	0
disruption	0
of	0
hydrogen	1
bonding	0
between	0
Gln223	0
and	0
Glu441	0
,	0
leading	0
Ser198	0
and	0
His438	0
to	0
move	0
away	0
from	0
each	0
other	0
with	0
subsequent	0
disruption	0
of	0
the	0
catalytic	0
triad	0
functionality	0
regardless	0
of	0
the	0
type	0
of	0
substrate	0
.	0

MD	0
also	0
showed	0
that	0
the	0
enzyme	0
volume	0
is	0
increased	0
,	0
suggesting	0
a	0
pre	0
-	0
denaturation	0
state	0
.	0

This	0
fits	0
with	0
the	0
reduced	0
concentration	0
of	0
p	0
.	0
Ala204Asp	0
/	0
p	0
.	0
Asp70Gly	0
-	0
p	0
.	0
Ala539Thr	0
tetrameric	0
enzyme	0
in	0
the	0
plasma	0
and	0
non	0
-	0
detectable	0
fast	0
moving	0
-	0
bands	0
on	0
electrophoresis	0
gels	0
.	0

Delayed	0
anemia	3
after	0
treatment	0
with	0
injectable	0
artesunate	1
in	0
the	0
Democratic	0
Republic	0
of	0
the	0
Congo	0
:	0
a	0
manageable	0
issue	0
.	0

Cases	0
of	0
delayed	0
hemolytic	3
anemia	4
have	0
been	0
described	0
after	0
treatment	0
with	0
injectable	0
artesunate	1
,	0
the	0
current	0
World	0
Health	0
0rganization	0
(	0
WH0	0
)	0
-	0
recommended	0
first	0
-	0
line	0
drug	0
for	0
the	0
treatment	0
of	0
severe	0
malaria	3
.	0

A	0
total	0
of	0
350	0
patients	0
(	0
215	0
[	0
61	0
.	0
4	0
%	0
]	0
<	0
5	0
years	0
of	0
age	0
and	0
135	0
[	0
38	0
.	0
6	0
%	0
]	0
>	0
5	0
years	0
of	0
age	0
)	0
were	0
followed	0
-	0
up	0
after	0
treatment	0
with	0
injectable	0
artesunate	1
for	0
severe	0
malaria	3
in	0
hospitals	0
and	0
health	0
centers	0
of	0
the	0
Democratic	0
Republic	0
of	0
the	0
Congo	0
.	0

Complete	0
series	0
of	0
hemoglobin	0
(	0
Hb	0
)	0
measurements	0
were	0
available	0
for	0
201	0
patients	0
.	0

A	0
decrease	0
in	0
Hb	0
levels	0
between	0
2	0
and	0
5	0
g	0
/	0
dL	0
was	0
detected	0
in	0
23	0
(	0
11	0
.	0
4	0
%	0
)	0
patients	0
during	0
the	0
follow	0
-	0
up	0
period	0
.	0

For	0
five	0
patients	0
,	0
Hb	0
levels	0
decreased	0
below	0
5	0
g	0
/	0
dL	0
during	0
at	0
least	0
one	0
follow	0
-	0
up	0
visit	0
.	0

All	0
cases	0
of	0
delayed	0
anemia	3
were	0
clinically	0
manageable	0
and	0
resolved	0
within	0
one	0
month	0
.	0

Regulation	0
of	0
signal	0
transducer	0
and	0
activator	0
of	0
transcription	0
3	0
and	0
apoptotic	0
pathways	0
by	0
betaine	1
attenuates	0
isoproterenol	1
-	0
induced	0
acute	0
myocardial	3
injury	4
in	0
rats	0
.	0

The	0
present	0
study	0
was	0
designed	0
to	0
investigate	0
the	0
cardioprotective	0
effects	0
of	0
betaine	1
on	0
acute	0
myocardial	3
ischemia	4
induced	0
experimentally	0
in	0
rats	0
focusing	0
on	0
regulation	0
of	0
signal	0
transducer	0
and	0
activator	0
of	0
transcription	0
3	0
(	0
STAT3	0
)	0
and	0
apoptotic	0
pathways	0
as	0
the	0
potential	0
mechanism	0
underlying	0
the	0
drug	0
effect	0
.	0

Male	0
Sprague	0
Dawley	0
rats	0
were	0
treated	0
with	0
betaine	1
(	0
100	0
,	0
200	0
,	0
and	0
400	0
mg	0
/	0
kg	0
)	0
orally	0
for	0
40	0
days	0
.	0

Acute	0
myocardial	3
ischemic	4
injury	4
was	0
induced	0
in	0
rats	0
by	0
subcutaneous	0
injection	0
of	0
isoproterenol	1
(	0
85	0
mg	0
/	0
kg	0
)	0
,	0
for	0
two	0
consecutive	0
days	0
.	0

Serum	0
cardiac	0
marker	0
enzyme	0
,	0
histopathological	0
variables	0
and	0
expression	0
of	0
protein	0
levels	0
were	0
analyzed	0
.	0

0ral	0
administration	0
of	0
betaine	1
(	0
200	0
and	0
400	0
mg	0
/	0
kg	0
)	0
significantly	0
reduced	0
the	0
level	0
of	0
cardiac	0
marker	0
enzyme	0
in	0
the	0
serum	0
and	0
prevented	0
left	0
ventricular	3
remodeling	4
.	0

Western	0
blot	0
analysis	0
showed	0
that	0
isoproterenol	1
-	0
induced	0
phosphorylation	0
of	0
STAT3	0
was	0
maintained	0
or	0
further	0
enhanced	0
by	0
betaine	1
treatment	0
in	0
myocardium	0
.	0

Furthermore	0
,	0
betaine	1
(	0
200	0
and	0
400	0
mg	0
/	0
kg	0
)	0
treatment	0
increased	0
the	0
ventricular	0
expression	0
of	0
Bcl	0
-	0
2	0
and	0
reduced	0
the	0
level	0
of	0
Bax	0
,	0
therefore	0
causing	0
a	0
significant	0
increase	0
in	0
the	0
ratio	0
of	0
Bcl	0
-	0
2	0
/	0
Bax	0
.	0

The	0
protective	0
role	0
of	0
betaine	1
on	0
myocardial	3
damage	4
was	0
further	0
confirmed	0
by	0
histopathological	0
examination	0
.	0

In	0
summary	0
,	0
our	0
results	0
showed	0
that	0
betaine	1
pretreatment	0
attenuated	0
isoproterenol	1
-	0
induced	0
acute	0
myocardial	3
ischemia	4
via	0
the	0
regulation	0
of	0
STAT3	0
and	0
apoptotic	0
pathways	0
.	0

Quetiapine	1
-	0
induced	0
neutropenia	3
in	0
a	0
bipolar	3
patient	0
with	0
hepatocellular	3
carcinoma	4
.	0

0BJECTIVE	0
:	0
Quetiapine	1
is	0
a	0
dibenzothiazepine	0
derivative	0
,	0
similar	0
to	0
clozapine	1
,	0
which	0
has	0
the	0
highest	0
risk	0
of	0
causing	0
blood	3
dyscrasias	4
,	0
especially	0
neutropenia	3
.	0

There	0
are	0
some	0
case	0
reports	0
about	0
this	0
side	0
effect	0
of	0
quetiapine	1
,	0
but	0
possible	0
risk	0
factors	0
are	0
seldom	0
discussed	0
and	0
identified	0
.	0

A	0
case	0
of	0
a	0
patient	0
with	0
hepatocellular	3
carcinoma	4
that	0
developed	0
neutropenia	3
after	0
treatment	0
with	0
quetiapine	1
is	0
described	0
here	0
.	0

CASE	0
REP0RT	0
:	0
A	0
62	0
-	0
year	0
-	0
old	0
Taiwanese	0
widow	0
with	0
bipolar	3
disorder	4
was	0
diagnosed	0
with	0
hepatocellular	3
carcinoma	4
at	0
age	0
60	0
.	0

She	0
developed	0
leucopenia	3
after	0
being	0
treated	0
with	0
quetiapine	1
.	0

After	0
quetiapine	1
was	0
discontinued	0
,	0
her	0
white	0
blood	0
cell	0
count	0
returned	0
to	0
normal	0
.	0

C0NCLUSI0NS	0
:	0
Although	0
neutropenia	3
is	0
not	0
a	0
common	0
side	0
effect	0
of	0
quetiapine	1
,	0
physicians	0
should	0
be	0
cautious	0
about	0
its	0
presentation	0
and	0
associated	0
risk	0
factors	0
.	0

Hepatic	3
dysfunction	4
may	0
be	0
one	0
of	0
the	0
possible	0
risk	0
factors	0
,	0
and	0
concomitant	0
fever	3
may	0
be	0
a	0
diagnostic	0
marker	0
for	0
adverse	0
reaction	0
to	0
quetiapine	1
.	0

Lateral	0
antebrachial	0
cutaneous	0
neuropathy	3
after	0
steroid	1
injection	0
at	0
lateral	0
epicondyle	0
.	0

BACKGR0UND	0
AND	0
0BJECTIVES	0
:	0
This	0
report	0
aimed	0
to	0
present	0
a	0
case	0
of	0
lateral	0
antebrachial	0
cutaneous	0
neuropathy	3
(	0
LACNP	0
)	0
that	0
occurred	0
after	0
a	0
steroid	1
injection	0
in	0
the	0
lateral	0
epicondyle	0
to	0
treat	0
lateral	3
epicondylitis	4
in	0
a	0
40	0
-	0
year	0
-	0
old	0
woman	0
.	0

MATERIAL	0
AND	0
METH0D	0
:	0
A	0
40	0
-	0
year	0
-	0
old	0
woman	0
presented	0
with	0
decreased	0
sensation	0
and	0
paresthesia	3
over	0
her	0
right	0
lateral	0
forearm	0
;	0
the	0
paresthesia	3
had	0
occurred	0
after	0
a	0
steroid	1
injection	0
in	0
the	0
right	0
lateral	0
epicondyle	0
3	0
months	0
before	0
.	0

Her	0
sensation	0
of	0
light	0
touch	0
and	0
pain	3
was	0
diminished	0
over	0
the	0
lateral	0
side	0
of	0
the	0
right	0
forearm	0
and	0
wrist	0
area	0
.	0

RESULTS	0
:	0
The	0
sensory	0
action	0
potential	0
amplitude	0
of	0
the	0
right	0
lateral	0
antebrachial	0
cutaneous	0
nerve	0
(	0
LACN	0
)	0
(	0
6	0
.	0
2	0
uV	0
)	0
was	0
lower	0
than	0
that	0
of	0
the	0
left	0
(	0
13	0
.	0
1	0
uV	0
)	0
.	0

The	0
difference	0
of	0
amplitude	0
between	0
both	0
sides	0
was	0
significant	0
because	0
there	0
was	0
more	0
than	0
a	0
50	0
%	0
reduction	0
.	0

She	0
was	0
diagnosed	0
with	0
right	0
LACNP	0
(	0
mainly	0
axonal	0
involvement	0
)	0
on	0
the	0
basis	0
of	0
the	0
clinical	0
manifestation	0
and	0
the	0
electrodiagnostic	0
findings	0
.	0

Her	0
symptoms	0
improved	0
through	0
physical	0
therapy	0
but	0
persisted	0
to	0
some	0
degree	0
.	0

C0NCLUSI0N	0
:	0
This	0
report	0
describes	0
the	0
case	0
of	0
a	0
woman	0
with	0
LACNP	0
that	0
developed	0
after	0
a	0
steroid	1
injection	0
for	0
the	0
treatment	0
of	0
lateral	3
epicondylitis	4
.	0

An	0
electrodiagnostic	0
study	0
,	0
including	0
a	0
nerve	0
conduction	0
study	0
of	0
the	0
LACN	0
,	0
was	0
helpful	0
to	0
diagnose	0
right	0
LACNP	0
and	0
to	0
find	0
the	0
passage	0
of	0
the	0
LACN	0
on	0
the	0
lateral	0
epicondyle	0
.	0

Curcumin	1
prevents	0
maleate	1
-	0
induced	0
nephrotoxicity	3
:	0
relation	0
to	0
hemodynamic	0
alterations	0
,	0
oxidative	0
stress	0
,	0
mitochondrial	0
oxygen	1
consumption	0
and	0
activity	0
of	0
respiratory	0
complex	0
I	0
.	0

The	0
potential	0
protective	0
effect	0
of	0
the	0
dietary	0
antioxidant	0
curcumin	1
(	0
120	0
mg	0
/	0
Kg	0
/	0
day	0
for	0
6	0
days	0
)	0
against	0
the	0
renal	3
injury	4
induced	0
by	0
maleate	1
was	0
evaluated	0
.	0

Tubular	0
proteinuria	3
and	0
oxidative	0
stress	0
were	0
induced	0
by	0
a	0
single	0
injection	0
of	0
maleate	1
(	0
400	0
mg	0
/	0
kg	0
)	0
in	0
rats	0
.	0

Maleate	1
-	0
induced	0
renal	3
injury	4
included	0
increase	0
in	0
renal	0
vascular	0
resistance	0
and	0
in	0
the	0
urinary	0
excretion	0
of	0
total	0
protein	0
,	0
glucose	1
,	0
sodium	1
,	0
neutrophil	0
gelatinase	0
-	0
associated	0
lipocalin	0
(	0
NGAL	0
)	0
and	0
N	0
-	0
acetyl	0
b	0
-	0
D	0
-	0
glucosaminidase	0
(	0
NAG	0
)	0
,	0
upregulation	0
of	0
kidney	3
injury	4
molecule	0
(	0
KIM	0
)	0
-	0
1	0
,	0
decrease	0
in	0
renal	0
blood	0
flow	0
and	0
claudin	0
-	0
2	0
expression	0
besides	0
of	0
necrosis	3
and	0
apoptosis	0
of	0
tubular	0
cells	0
on	0
24	0
h	0
.	0

0xidative	0
stress	0
was	0
determined	0
by	0
measuring	0
the	0
oxidation	0
of	0
lipids	0
and	0
proteins	0
and	0
diminution	0
in	0
renal	0
Nrf2	0
levels	0
.	0

Studies	0
were	0
also	0
conducted	0
in	0
renal	0
epithelial	0
LLC	0
-	0
PK1	0
cells	0
and	0
in	0
mitochondria	0
isolated	0
from	0
kidneys	0
of	0
all	0
the	0
experimental	0
groups	0
.	0

Maleate	1
induced	0
cell	0
damage	0
and	0
reactive	0
oxygen	1
species	0
(	0
R0S	0
)	0
production	0
in	0
LLC	0
-	0
PK1	0
cells	0
in	0
culture	0
.	0

In	0
addition	0
,	0
maleate	1
treatment	0
reduced	0
oxygen	1
consumption	0
in	0
ADP	1
-	0
stimulated	0
mitochondria	0
and	0
diminished	0
respiratory	0
control	0
index	0
when	0
using	0
malate	1
/	0
glutamate	1
as	0
substrate	0
.	0

The	0
activities	0
of	0
both	0
complex	0
I	0
and	0
aconitase	0
were	0
also	0
diminished	0
.	0

All	0
the	0
above	0
-	0
described	0
alterations	0
were	0
prevented	0
by	0
curcumin	1
.	0

It	0
is	0
concluded	0
that	0
curcumin	1
is	0
able	0
to	0
attenuate	0
in	0
vivo	0
maleate	1
-	0
induced	0
nephropathy	3
and	0
in	0
vitro	0
cell	0
damage	0
.	0

The	0
in	0
vivo	0
protection	0
was	0
associated	0
to	0
the	0
prevention	0
of	0
oxidative	0
stress	0
and	0
preservation	0
of	0
mitochondrial	0
oxygen	1
consumption	0
and	0
activity	0
of	0
respiratory	0
complex	0
I	0
,	0
and	0
the	0
in	0
vitro	0
protection	0
was	0
associated	0
to	0
the	0
prevention	0
of	0
R0S	0
production	0
.	0

Anticonvulsant	0
actions	0
of	0
MK	1
-	2
801	2
on	0
the	0
lithium	1
-	0
pilocarpine	1
model	0
of	0
status	3
epilepticus	4
in	0
rats	0
.	0

MK	1
-	2
801	2
,	0
a	0
noncompetitive	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
(	0
NMDA	1
)	0
receptor	0
antagonist	0
,	0
was	0
tested	0
for	0
anticonvulsant	0
effects	0
in	0
rats	0
using	0
two	0
seizure	3
models	0
,	0
coadministration	0
of	0
lithium	1
and	0
pilocarpine	1
and	0
administration	0
of	0
a	0
high	0
dose	0
of	0
pilocarpine	1
alone	0
.	0

Three	0
major	0
results	0
are	0
reported	0
.	0

First	0
,	0
pretreatment	0
with	0
MK	1
-	2
801	2
produced	0
an	0
effective	0
and	0
dose	0
-	0
dependent	0
anticonvulsant	0
action	0
with	0
the	0
lithium	1
-	0
pilocarpine	1
model	0
but	0
not	0
with	0
rats	0
treated	0
with	0
pilocarpine	1
alone	0
,	0
suggesting	0
that	0
different	0
biochemical	0
mechanisms	0
control	0
seizures	3
in	0
these	0
two	0
models	0
.	0

Second	0
,	0
the	0
anticonvulsant	0
effect	0
of	0
MK	1
-	2
801	2
in	0
the	0
lithium	1
-	0
pilocarpine	1
model	0
only	0
occurred	0
after	0
initial	0
periods	0
of	0
seizure	3
activity	0
.	0

This	0
observation	0
is	0
suggested	0
to	0
be	0
an	0
in	0
vivo	0
demonstration	0
of	0
the	0
conclusion	0
derived	0
from	0
in	0
vitro	0
experiments	0
that	0
MK	1
-	2
801	2
binding	0
requires	0
agonist	0
-	0
induced	0
opening	0
of	0
the	0
channel	0
sites	0
of	0
the	0
NMDA	1
receptor	0
.	0

Third	0
,	0
although	0
it	0
is	0
relatively	0
easy	0
to	0
block	0
seizures	3
induced	0
by	0
lithium	1
and	0
pilocarpine	1
by	0
administration	0
of	0
anticonvulsants	0
prior	0
to	0
pilocarpine	1
,	0
it	0
is	0
more	0
difficult	0
to	0
terminate	0
ongoing	0
status	3
epilepticus	4
and	0
block	0
the	0
lethality	0
of	0
the	0
seizures	3
.	0

Administration	0
of	0
MK	1
-	2
801	2
30	0
or	0
60	0
min	0
after	0
pilocarpine	1
,	0
i	0
.	0
e	0
.	0
,	0
during	0
status	3
epilepticus	4
,	0
gradually	0
reduced	0
electrical	0
and	0
behavioral	0
seizure	3
activity	0
and	0
greatly	0
enhanced	0
the	0
survival	0
rate	0
.	0

These	0
results	0
suggest	0
that	0
activation	0
of	0
NMDA	1
receptors	0
plays	0
an	0
important	0
role	0
in	0
status	3
epilepticus	4
and	0
brain	3
damage	4
in	0
the	0
lithium	1
-	0
pilocarpine	1
model	0
.	0

This	0
was	0
further	0
supported	0
by	0
results	0
showing	0
that	0
nonconvulsive	0
doses	0
of	0
NMDA	1
and	0
pilocarpine	1
were	0
synergistic	0
,	0
resulting	0
in	0
status	3
epilepticus	4
and	0
subsequent	0
mortality	0
.	0

Continuous	0
infusion	0
tobramycin	1
combined	0
with	0
carbenicillin	1
for	0
infections	3
in	0
cancer	3
patients	0
.	0

The	0
cure	0
rate	0
of	0
infections	3
in	0
cancer	3
patients	0
is	0
adversely	0
affected	0
by	0
neutropenia	3
(	0
less	0
than	0
1	0
,	0
000	0
/	0
mm3	0
)	0
.	0

In	0
particular	0
,	0
patients	0
with	0
severe	0
neutropenia	3
(	0
less	0
than	0
100	0
/	0
mm3	0
)	0
have	0
shown	0
a	0
poor	0
response	0
to	0
antibiotics	0
.	0

To	0
overcome	0
the	0
adverse	0
effects	0
of	0
neutropenia	3
,	0
tobramycin	1
was	0
given	0
by	0
continuous	0
infusion	0
and	0
combined	0
with	0
intermittent	0
carbenicillin	1
.	0

Tobramycin	1
was	0
given	0
to	0
a	0
total	0
daily	0
dose	0
of	0
300	0
mg	0
/	0
m2	0
and	0
carbenicillin	1
was	0
given	0
at	0
a	0
dose	0
of	0
5	0
gm	0
every	0
four	0
hours	0
.	0

There	0
were	0
125	0
infectious	0
episodes	0
in	0
116	0
cancer	3
patients	0
receiving	0
myelosuppressive	0
chemotherapy	0
.	0

The	0
overall	0
cure	0
rate	0
was	0
70	0
%	0
.	0

Pneumonia	3
was	0
the	0
most	0
common	0
infection	3
and	0
61	0
%	0
of	0
59	0
episodes	0
were	0
cured	0
.	0

Gram	0
-	0
negative	0
bacilli	0
were	0
the	0
most	0
common	0
causative	0
organisms	0
and	0
69	0
%	0
of	0
these	0
infections	3
were	0
cured	0
.	0

The	0
most	0
common	0
pathogen	0
was	0
Klebsiella	0
pneumoniae	3
and	0
this	0
,	0
together	0
with	0
Escherichia	0
coli	0
and	0
Pseudomonas	0
aeruginosa	0
,	0
accounted	0
for	0
74	0
%	0
of	0
all	0
gram	3
-	4
negative	4
bacillary	4
infections	4
.	0

Response	0
was	0
not	0
influenced	0
by	0
the	0
initial	0
neutrophil	0
count	0
,	0
with	0
a	0
62	0
%	0
cure	0
rate	0
for	0
39	0
episodes	0
associated	0
with	0
severe	0
neutropenia	3
.	0

However	0
,	0
failure	0
of	0
the	0
neutrophil	0
count	0
to	0
increase	0
during	0
therapy	0
adversely	0
affected	0
response	0
.	0

Azotemia	3
was	0
the	0
major	0
side	0
effect	0
recognized	0
,	0
and	0
it	0
occurred	0
in	0
11	0
%	0
of	0
episodes	0
.	0

Major	0
azotemia	3
(	0
serum	0
creatinine	1
greater	0
than	0
2	0
.	0
5	0
mg	0
/	0
dl	0
or	0
BUN	0
greater	0
than	0
50	0
mg	0
/	0
dl	0
)	0
occurred	0
in	0
only	0
2	0
%	0
.	0

Azotemia	3
was	0
not	0
related	0
to	0
duration	0
of	0
therapy	0
or	0
serum	0
tobramycin	1
concentration	0
.	0

This	0
antibiotic	0
regimen	0
showed	0
both	0
therapeutic	0
efficacy	0
and	0
acceptable	0
renal	3
toxicity	4
for	0
these	0
patients	0
.	0

Incidence	0
of	0
solid	0
tumours	3
among	0
pesticide	0
applicators	0
exposed	0
to	0
the	0
organophosphate	1
insecticide	0
diazinon	1
in	0
the	0
Agricultural	0
Health	0
Study	0
:	0
an	0
updated	0
analysis	0
.	0

0BJECTIVE	0
:	0
Diazinon	1
,	0
a	0
common	0
organophosphate	1
insecticide	0
with	0
genotoxic	0
properties	0
,	0
was	0
previously	0
associated	0
with	0
lung	3
cancer	4
in	0
the	0
Agricultural	0
Health	0
Study	0
(	0
AHS	0
)	0
cohort	0
,	0
but	0
few	0
other	0
epidemiological	0
studies	0
have	0
examined	0
diazinon	1
-	0
associated	0
cancer	3
risk	0
.	0

We	0
used	0
updated	0
diazinon	1
exposure	0
and	0
cancer	3
incidence	0
information	0
to	0
evaluate	0
solid	0
tumour	3
risk	0
in	0
the	0
AHS	0
.	0

METH0DS	0
:	0
Male	0
pesticide	0
applicators	0
in	0
Iowa	0
and	0
North	0
Carolina	0
reported	0
lifetime	0
diazinon	1
use	0
at	0
enrolment	0
(	0
1993	0
-	0
1997	0
)	0
and	0
follow	0
-	0
up	0
(	0
1998	0
-	0
2005	0
)	0
;	0
cancer	3
incidence	0
was	0
assessed	0
through	0
2010	0
(	0
North	0
Carolina	0
)	0
/	0
2011	0
(	0
Iowa	0
)	0
.	0

Among	0
applicators	0
with	0
usage	0
information	0
sufficient	0
to	0
evaluate	0
exposure	0
-	0
response	0
patterns	0
,	0
we	0
used	0
Poisson	0
regression	0
to	0
estimate	0
adjusted	0
rate	0
ratios	0
(	0
RRs	0
)	0
and	0
95	0
%	0
CI	0
for	0
cancer	3
sites	0
with	0
>	0
10	0
exposed	0
cases	0
for	0
both	0
lifetime	0
(	0
LT	0
)	0
exposure	0
days	0
and	0
intensity	0
-	0
weighted	0
(	0
IW	0
)	0
lifetime	0
exposure	0
days	0
(	0
accounting	0
for	0
factors	0
impacting	0
exposure	0
)	0
.	0

RESULTS	0
:	0
We	0
observed	0
elevated	0
lung	3
cancer	4
risks	0
(	0
N	0
=	0
283	0
)	0
among	0
applicators	0
with	0
the	0
greatest	0
number	0
of	0
LT	0
(	0
RR	0
=	0
1	0
.	0
60	0
;	0
95	0
%	0
CI	0
1	0
.	0
11	0
to	0
2	0
.	0
31	0
;	0
Ptrend	0
=	0
0	0
.	0
02	0
)	0
and	0
IW	0
days	0
of	0
diazinon	1
use	0
(	0
RR	0
=	0
1	0
.	0
41	0
;	0
95	0
%	0
CI	0
0	0
.	0
98	0
to	0
2	0
.	0
04	0
;	0
Ptrend	0
=	0
0	0
.	0
08	0
)	0
.	0

Kidney	3
cancer	4
(	0
N	0
=	0
94	0
)	0
risks	0
were	0
non	0
-	0
significantly	0
elevated	0
(	0
RRLT	0
days	0
=	0
1	0
.	0
77	0
;	0
95	0
%	0
CI	0
0	0
.	0
90	0
to	0
3	0
.	0
51	0
;	0
Ptrend	0
=	0
0	0
.	0
09	0
;	0
RRIW	0
days	0
1	0
.	0
37	0
;	0
95	0
%	0
CI	0
0	0
.	0
64	0
to	0
2	0
.	0
92	0
;	0
Ptrend	0
=	0
0	0
.	0
50	0
)	0
,	0
as	0
were	0
risks	0
for	0
aggressive	0
prostate	3
cancer	4
(	0
N	0
=	0
656	0
)	0
.	0

C0NCLUSI0NS	0
:	0
0ur	0
updated	0
evaluation	0
of	0
diazinon	1
provides	0
additional	0
evidence	0
of	0
an	0
association	0
with	0
lung	3
cancer	4
risk	0
.	0

Newly	0
identified	0
links	0
to	0
kidney	3
cancer	4
and	0
associations	0
with	0
aggressive	0
prostate	3
cancer	4
require	0
further	0
evaluation	0
.	0

Associations	0
of	0
0zone	1
and	0
PM2	0
.	0
5	0
Concentrations	0
With	0
Parkinson	3
'	4
s	4
Disease	4
Among	0
Participants	0
in	0
the	0
Agricultural	0
Health	0
Study	0
.	0

0BJECTIVE	0
:	0
This	0
study	0
describes	0
associations	0
of	0
ozone	1
and	0
fine	0
particulate	1
matter	2
with	0
Parkinson	3
'	4
s	4
disease	4
observed	0
among	0
farmers	0
in	0
North	0
Carolina	0
and	0
Iowa	0
.	0

METH0DS	0
:	0
We	0
used	0
logistic	0
regression	0
to	0
determine	0
the	0
associations	0
of	0
these	0
pollutants	0
with	0
self	0
-	0
reported	0
,	0
doctor	0
-	0
diagnosed	0
Parkinson	3
'	4
s	4
disease	4
.	0

Daily	0
predicted	0
pollutant	0
concentrations	0
were	0
used	0
to	0
derive	0
surrogates	0
of	0
long	0
-	0
term	0
exposure	0
and	0
link	0
them	0
to	0
study	0
participants	0
'	0
geocoded	0
addresses	0
.	0

RESULTS	0
:	0
We	0
observed	0
positive	0
associations	0
of	0
Parkinson	3
'	4
s	4
disease	4
with	0
ozone	1
(	0
odds	0
ratio	0
=	0
1	0
.	0
39	0
;	0
95	0
%	0
CI	0
:	0
0	0
.	0
98	0
to	0
1	0
.	0
98	0
)	0
and	0
fine	0
particulate	1
matter	2
(	0
odds	0
ratio	0
=	0
1	0
.	0
34	0
;	0
95	0
%	0
CI	0
:	0
0	0
.	0
93	0
to	0
1	0
.	0
93	0
)	0
in	0
North	0
Carolina	0
but	0
not	0
in	0
Iowa	0
.	0

C0NCLUSI0NS	0
:	0
The	0
plausibility	0
of	0
an	0
effect	0
of	0
ambient	0
concentrations	0
of	0
these	0
pollutants	0
on	0
Parkinson	3
'	4
s	4
disease	4
risk	0
is	0
supported	0
by	0
experimental	0
data	0
demonstrating	0
damage	0
to	0
dopaminergic	0
neurons	0
at	0
relevant	0
concentrations	0
.	0

Additional	0
studies	0
are	0
needed	0
to	0
address	0
uncertainties	0
related	0
to	0
confounding	0
and	0
to	0
examine	0
temporal	0
aspects	0
of	0
the	0
associations	0
we	0
observed	0
.	0

Low	0
functional	0
programming	0
of	0
renal	0
AT2R	0
mediates	0
the	0
developmental	0
origin	0
of	0
glomerulosclerosis	3
in	0
adult	0
offspring	0
induced	0
by	0
prenatal	0
caffeine	1
exposure	0
.	0

UNASSIGNED	0
:	0
0ur	0
previous	0
study	0
has	0
indicated	0
that	0
prenatal	0
caffeine	1
exposure	0
(	0
PCE	0
)	0
could	0
induce	0
intrauterine	3
growth	4
retardation	4
(	0
IUGR	3
)	0
of	0
offspring	0
.	0

Recent	0
research	0
suggested	0
that	0
IUGR	3
is	0
a	0
risk	0
factor	0
for	0
glomerulosclerosis	3
.	0

However	0
,	0
whether	0
PCE	0
could	0
induce	0
glomerulosclerosis	3
and	0
its	0
underlying	0
mechanisms	0
remain	0
unknown	0
.	0

This	0
study	0
aimed	0
to	0
demonstrate	0
the	0
induction	0
to	0
glomerulosclerosis	3
in	0
adult	0
offspring	0
by	0
PCE	0
and	0
its	0
intrauterine	0
programming	0
mechanisms	0
.	0

A	0
rat	0
model	0
of	0
IUGR	3
was	0
established	0
by	0
PCE	0
,	0
male	0
fetuses	0
and	0
adult	0
offspring	0
at	0
the	0
age	0
of	0
postnatal	0
week	0
24	0
were	0
euthanized	0
.	0

The	0
results	0
revealed	0
that	0
the	0
adult	0
offspring	0
kidneys	0
in	0
the	0
PCE	0
group	0
exhibited	0
glomerulosclerosis	3
as	0
well	0
as	0
interstitial	3
fibrosis	4
,	0
accompanied	0
by	0
elevated	0
levels	0
of	0
serum	0
creatinine	1
and	0
urine	0
protein	0
.	0

Renal	0
angiotensin	1
II	2
receptor	0
type	0
2	0
(	0
AT2R	0
)	0
gene	0
expression	0
in	0
adult	0
offspring	0
was	0
reduced	0
by	0
PCE	0
,	0
whereas	0
the	0
renal	0
angiotensin	1
II	2
receptor	0
type	0
1a	0
(	0
AT1aR	0
)	0
/	0
AT2R	0
expression	0
ratio	0
was	0
increased	0
.	0

The	0
fetal	0
kidneys	0
in	0
the	0
PCE	0
group	0
displayed	0
an	0
enlarged	0
Bowman	0
'	0
s	0
space	0
and	0
a	0
shrunken	0
glomerular	0
tuft	0
,	0
accompanied	0
by	0
a	0
reduced	0
cortex	0
width	0
and	0
an	0
increase	0
in	0
the	0
nephrogenic	0
zone	0
/	0
cortical	0
zone	0
ratio	0
.	0

0bservation	0
by	0
electronic	0
microscope	0
revealed	0
structural	0
damage	0
of	0
podocytes	0
;	0
the	0
reduced	0
expression	0
level	0
of	0
podocyte	0
marker	0
genes	0
,	0
nephrin	0
and	0
podocin	0
,	0
was	0
also	0
detected	0
by	0
q	0
-	0
PCR	0
.	0

Moreover	0
,	0
AT2R	0
gene	0
and	0
protein	0
expressions	0
in	0
fetal	0
kidneys	0
were	0
inhibited	0
by	0
PCE	0
,	0
associated	0
with	0
the	0
repression	0
of	0
the	0
gene	0
expression	0
of	0
glial	0
-	0
cell	0
-	0
line	0
-	0
derived	0
neurotrophic	0
factor	0
(	0
GDNF	0
)	0
/	0
tyrosine	1
kinase	0
receptor	0
(	0
c	0
-	0
Ret	0
)	0
signaling	0
pathway	0
.	0

These	0
results	0
demonstrated	0
that	0
PCE	0
could	0
induce	0
dysplasia	3
of	4
fetal	4
kidneys	4
as	0
well	0
as	0
glomerulosclerosis	3
of	0
adult	0
offspring	0
,	0
and	0
the	0
low	0
functional	0
programming	0
of	0
renal	0
AT2R	0
might	0
mediate	0
the	0
developmental	0
origin	0
of	0
adult	0
glomerulosclerosis	3
.	0

1	1
,	2
3	2
-	2
Butadiene	2
,	0
CML	3
and	0
the	0
t	0
(	0
9	0
:	0
22	0
)	0
translocation	0
:	0
A	0
reality	0
check	0
.	0

UNASSIGNED	0
:	0
Epidemiological	0
studies	0
of	0
1	1
,	2
3	2
-	2
butadiene	2
have	0
suggest	0
that	0
exposures	0
to	0
humans	0
are	0
associated	0
with	0
chronic	3
myeloid	4
leukemia	4
(	0
CML	3
)	0
.	0

CML	3
has	0
a	0
well	0
-	0
documented	0
association	0
with	0
ionizing	0
radiation	0
,	0
but	0
reports	0
of	0
associations	0
with	0
chemical	0
exposures	0
have	0
been	0
questioned	0
.	0

Ionizing	0
radiation	0
is	0
capable	0
of	0
inducing	0
the	0
requisite	0
CML	3
-	0
associated	0
t	0
(	0
9	0
:	0
22	0
)	0
translocation	0
(	0
Philadelphia	3
chromosome	4
)	0
in	0
appropriate	0
cells	0
in	0
vitro	0
but	0
,	0
thus	0
far	0
,	0
chemicals	0
have	0
not	0
shown	0
this	0
capacity	0
.	0

We	0
have	0
proposed	0
that	0
1	1
,	2
3	2
-	2
butadiene	2
metabolites	0
be	0
so	0
tested	0
as	0
a	0
reality	0
check	0
on	0
the	0
epidemiological	0
reports	0
.	0

In	0
order	0
to	0
conduct	0
reliable	0
testing	0
in	0
this	0
regard	0
,	0
it	0
is	0
essential	0
that	0
a	0
positive	0
control	0
for	0
induction	0
be	0
available	0
.	0

We	0
have	0
used	0
ionizing	0
radiation	0
to	0
develop	0
such	0
a	0
control	0
.	0

Results	0
described	0
here	0
demonstrate	0
that	0
this	0
agent	0
does	0
in	0
fact	0
induce	0
pathogenic	0
t	0
(	0
9	0
:	0
22	0
)	0
translocations	0
in	0
a	0
human	0
myeloid	0
cell	0
line	0
in	0
vitro	0
,	0
but	0
does	0
so	0
at	0
low	0
frequencies	0
.	0

Conditions	0
that	0
will	0
be	0
required	0
for	0
studies	0
of	0
1	1
,	2
3	2
-	2
butadiene	2
are	0
discussed	0
.	0

Cancer	3
incidence	0
and	0
metolachlor	1
use	0
in	0
the	0
Agricultural	0
Health	0
Study	0
:	0
An	0
update	0
.	0

UNASSIGNED	0
:	0
Metolachlor	1
,	0
a	0
widely	0
used	0
herbicide	0
,	0
is	0
classified	0
as	0
a	0
Group	0
C	0
carcinogen	0
by	0
the	0
U	0
.	0
S	0
.	0

Environmental	0
Protection	0
Agency	0
based	0
on	0
increased	0
liver	3
neoplasms	4
in	0
female	0
rats	0
.	0

Epidemiologic	0
studies	0
of	0
the	0
health	0
effects	0
of	0
metolachlor	1
have	0
been	0
limited	0
.	0

The	0
Agricultural	0
Health	0
Study	0
(	0
AHS	0
)	0
is	0
a	0
prospective	0
cohort	0
study	0
including	0
licensed	0
private	0
and	0
commercial	0
pesticide	0
applicators	0
in	0
Iowa	0
and	0
North	0
Carolina	0
enrolled	0
1993	0
-	0
1997	0
.	0

We	0
evaluated	0
cancer	3
incidence	0
through	0
2010	0
/	0
2011	0
(	0
NC	0
/	0
IA	0
)	0
for	0
49	0
,	0
616	0
applicators	0
,	0
53	0
%	0
of	0
whom	0
reported	0
ever	0
using	0
metolachlor	1
.	0

We	0
used	0
Poisson	0
regression	0
to	0
evaluate	0
relations	0
between	0
two	0
metrics	0
of	0
metolachlor	1
use	0
(	0
lifetime	0
days	0
,	0
intensity	0
-	0
weighted	0
lifetime	0
days	0
)	0
and	0
cancer	3
incidence	0
.	0

We	0
saw	0
no	0
association	0
between	0
metolachlor	1
use	0
and	0
incidence	0
of	0
all	0
cancers	3
combined	0
(	0
n	0
=	0
5	0
,	0
701	0
with	0
a	0
5	0
-	0
year	0
lag	0
)	0
or	0
most	0
site	0
-	0
specific	0
cancers	3
.	0

For	0
liver	3
cancer	4
,	0
in	0
analyses	0
restricted	0
to	0
exposed	0
workers	0
,	0
elevations	0
observed	0
at	0
higher	0
categories	0
of	0
use	0
were	0
not	0
statistically	0
significant	0
.	0

However	0
,	0
trends	0
for	0
both	0
lifetime	0
and	0
intensity	0
-	0
weighted	0
lifetime	0
days	0
of	0
metolachor	1
use	0
were	0
positive	0
and	0
statistically	0
significant	0
with	0
an	0
unexposed	0
reference	0
group	0
.	0

A	0
similar	0
pattern	0
was	0
observed	0
for	0
follicular	3
cell	4
lymphoma	4
,	0
but	0
no	0
other	0
lymphoma	3
subtypes	0
.	0

An	0
earlier	0
suggestion	0
of	0
increased	0
lung	3
cancer	4
risk	0
at	0
high	0
levels	0
of	0
metolachlor	1
use	0
in	0
this	0
cohort	0
was	0
not	0
confirmed	0
in	0
this	0
update	0
.	0

This	0
suggestion	0
of	0
an	0
association	0
between	0
metolachlor	1
and	0
liver	3
cancer	4
among	0
pesticide	0
applicators	0
is	0
a	0
novel	0
finding	0
and	0
echoes	0
observation	0
of	0
increased	0
liver	3
neoplasms	4
in	0
some	0
animal	0
studies	0
.	0

However	0
,	0
our	0
findings	0
for	0
both	0
liver	3
cancer	4
and	0
follicular	0
cell	0
lymphoma	3
warrant	0
follow	0
-	0
up	0
to	0
better	0
differentiate	0
effects	0
of	0
metolachlor	1
use	0
from	0
other	0
factors	0
.	0

Mechanisms	0
Underlying	0
Latent	0
Disease	0
Risk	0
Associated	0
with	0
Early	0
-	0
Life	0
Arsenic	1
Exposure	0
:	0
Current	0
Research	0
Trends	0
and	0
Scientific	0
Gaps	0
.	0

BACKGR0UND	0
:	0
Millions	0
of	0
individuals	0
worldwide	0
,	0
particularly	0
those	0
living	0
in	0
rural	0
and	0
developing	0
areas	0
,	0
are	0
exposed	0
to	0
harmful	0
levels	0
of	0
inorganic	1
arsenic	2
(	0
iAs	1
)	0
in	0
their	0
drinking	0
water	0
.	0

Inorganic	1
As	2
exposure	0
during	0
key	0
developmental	0
periods	0
is	0
associated	0
with	0
a	0
variety	0
of	0
adverse	0
health	0
effects	0
including	0
those	0
that	0
are	0
evident	0
in	0
adulthood	0
.	0

There	0
is	0
considerable	0
interest	0
in	0
identifying	0
the	0
molecular	0
mechanisms	0
that	0
relate	0
early	0
-	0
life	0
iAs	1
exposure	0
to	0
the	0
development	0
of	0
these	0
latent	0
diseases	0
,	0
particularly	0
in	0
relationship	0
to	0
cancer	3
.	0

0BJECTIVES	0
:	0
This	0
work	0
summarizes	0
research	0
on	0
the	0
molecular	0
mechanisms	0
that	0
underlie	0
the	0
increased	0
risk	0
of	0
cancer	3
development	0
in	0
adulthood	0
that	0
is	0
associated	0
with	0
early	0
-	0
life	0
iAs	1
exposure	0
.	0

DISCUSSI0N	0
:	0
Epigenetic	0
reprogramming	0
that	0
imparts	0
functional	0
changes	0
in	0
gene	0
expression	0
,	0
the	0
development	0
of	0
cancer	3
stem	0
cells	0
,	0
and	0
immunomodulation	0
are	0
plausible	0
underlying	0
mechanisms	0
by	0
which	0
early	0
-	0
life	0
iAs	1
exposure	0
elicits	0
latent	0
carcinogenic	0
effects	0
.	0

C0NCLUSI0NS	0
:	0
Evidence	0
is	0
mounting	0
that	0
relates	0
early	0
-	0
life	0
iAs	1
exposure	0
and	0
cancer	3
development	0
later	0
in	0
life	0
.	0

Future	0
research	0
should	0
include	0
animal	0
studies	0
that	0
address	0
mechanistic	0
hypotheses	0
and	0
studies	0
of	0
human	0
populations	0
that	0
integrate	0
early	0
-	0
life	0
exposure	0
,	0
molecular	0
alterations	0
,	0
and	0
latent	0
disease	0
outcomes	0
.	0

Nifedipine	1
induced	0
bradycardia	3
in	0
a	0
patient	0
with	0
autonomic	3
neuropathy	4
.	0

An	0
80	0
year	0
old	0
diabetic	3
male	0
with	0
evidence	0
of	0
peripheral	3
and	4
autonomic	4
neuropathy	4
was	0
admitted	0
with	0
chest	3
pain	4
.	0

He	0
was	0
found	0
to	0
have	0
atrial	3
flutter	4
at	0
a	0
ventricular	0
rate	0
of	0
70	0
/	0
min	0
which	0
slowed	0
down	0
to	0
30	0
-	0
40	0
/	0
min	0
when	0
nifedipine	1
(	0
60	0
mg	0
)	0
in	0
3	0
divided	0
doses	0
,	0
during	0
which	0
he	0
was	0
paced	0
at	0
a	0
rate	0
of	0
70	0
/	0
min	0
.	0

This	0
is	0
inconsistent	0
with	0
the	0
well	0
-	0
established	0
finding	0
that	0
nifedipine	1
induces	0
tachycardia	3
in	0
normally	0
innervated	0
hearts	0
.	0

However	0
,	0
in	0
hearts	0
deprived	0
of	0
compensatory	0
sympathetic	0
drive	0
,	0
it	0
may	0
lead	0
to	0
bradycardia	3
.	0

The	0
effect	0
of	0
haloperidol	1
in	0
cocaine	1
and	0
amphetamine	1
intoxication	0
.	0

The	0
effectiveness	0
of	0
haloperidol	1
pretreatment	0
in	0
preventing	0
the	0
toxic	0
effects	0
of	0
high	0
doses	0
of	0
amphetamine	1
and	0
cocaine	1
was	0
studied	0
in	0
rats	0
.	0

In	0
this	0
model	0
,	0
toxic	0
effects	0
were	0
induced	0
by	0
intraperitoneal	0
(	0
i	0
.	0
p	0
.	0
)	0
injection	0
of	0
amphetamine	1
75	0
mg	0
/	0
kg	0
(	0
100	0
%	0
death	0
rate	0
)	0
or	0
cocaine	1
70	0
mg	0
/	0
kg	0
(	0
82	0
%	0
death	0
rate	0
)	0
.	0

Haloperidol	1
failed	0
to	0
prevent	0
amphetamine	1
-	0
induced	0
seizures	3
,	0
but	0
did	0
lower	0
the	0
mortality	0
rate	0
at	0
most	0
doses	0
tested	0
.	0

Haloperidol	1
decreased	0
the	0
incidence	0
of	0
cocaine	1
-	0
induced	0
seizures	3
at	0
the	0
two	0
highest	0
doses	0
,	0
but	0
the	0
lowering	0
of	0
the	0
mortality	0
rate	0
did	0
not	0
reach	0
statistical	0
significance	0
at	0
any	0
dose	0
.	0

These	0
data	0
suggest	0
a	0
protective	0
role	0
for	0
the	0
central	0
dopamine	1
blocker	0
haloperidol	1
against	0
death	0
from	0
high	0
-	0
dose	0
amphetamine	1
exposure	0
without	0
reducing	0
the	0
incidence	0
of	0
seizures	3
.	0

In	0
contrast	0
,	0
haloperidol	1
demonstrated	0
an	0
ability	0
to	0
reduce	0
cocaine	1
-	0
induced	0
seizures	3
without	0
significantly	0
reducing	0
mortality	0
.	0

Autoradiographic	0
evidence	0
of	0
estrogen	1
binding	0
sites	0
in	0
nuclei	0
of	0
diethylstilbesterol	1
induced	0
hamster	0
renal	3
carcinomas	4
.	0

Estrogen	1
binding	0
sites	0
were	0
demonstrated	0
by	0
autoradiography	0
in	0
one	0
transplantable	0
and	0
five	0
primary	0
diethylstilbesterol	1
induced	0
renal	3
carcinomas	4
in	0
three	0
hamsters	0
.	0

Radiolabelling	0
,	0
following	0
the	0
in	0
vivo	0
injection	0
of	0
3H	0
-	0
17	0
beta	0
estradiol	1
,	0
was	0
increased	0
only	0
over	0
the	0
nuclei	0
of	0
tumor	3
cells	0
;	0
stereologic	0
analysis	0
revealed	0
a	0
4	0
.	0
5	0
-	0
to	0
6	0
.	0
7	0
-	0
times	0
higher	0
concentration	0
of	0
reduced	0
silver	1
grains	0
over	0
nuclei	0
than	0
cytoplasm	0
of	0
these	0
cells	0
.	0

Despite	0
rapid	0
tubular	0
excretion	0
of	0
estradiol	1
which	0
peaked	0
in	0
less	0
than	0
1	0
h	0
,	0
the	0
normal	0
cells	0
did	0
not	0
appear	0
to	0
bind	0
the	0
ligand	0
.	0

This	0
is	0
the	0
first	0
published	0
report	0
documenting	0
the	0
preferential	0
in	0
vivo	0
binding	0
of	0
estrogen	1
to	0
nuclei	0
of	0
cells	0
in	0
estrogen	1
induced	0
hamster	0
renal	3
carcinomas	4
.	0

Bradycardia	3
due	0
to	0
biperiden	1
.	0

In	0
a	0
38	0
-	0
year	0
-	0
old	0
male	0
patient	0
suffering	0
from	0
a	0
severe	0
postzosteric	3
trigeminal	3
neuralgia	4
,	0
intravenous	0
application	0
of	0
10	0
mg	0
biperiden	1
lactate	2
led	0
to	0
a	0
long	0
-	0
lasting	0
paradoxical	0
reaction	0
characterized	0
by	0
considerable	0
bradycardia	3
,	0
dysarthria	3
,	0
and	0
dysphagia	3
.	0

The	0
heart	0
rate	0
was	0
back	0
to	0
normal	0
within	0
12	0
hours	0
upon	0
administration	0
of	0
orciprenaline	1
under	0
cardiac	0
monitoring	0
in	0
an	0
intensive	0
care	0
unit	0
.	0

Bradycardia	3
induced	0
by	0
biperiden	1
is	0
attributed	0
to	0
the	0
speed	0
of	0
injection	0
and	0
to	0
a	0
dose	0
-	0
related	0
dual	0
effect	0
of	0
atropine	1
-	0
like	0
drugs	0
on	0
muscarine	1
receptors	0
.	0

Deliberate	0
hypotension	3
induced	0
by	0
labetalol	1
with	0
halothane	1
,	0
enflurane	1
or	0
isoflurane	1
for	0
middle	0
-	0
ear	0
surgery	0
.	0

The	0
feasibility	0
of	0
using	0
labetalol	1
,	0
an	0
alpha	0
-	0
and	0
beta	0
-	0
adrenergic	0
blocking	0
agent	0
,	0
as	0
a	0
hypotensive	3
agent	0
in	0
combination	0
with	0
inhalation	0
anaesthetics	0
(	0
halothane	1
,	0
enflurane	1
or	0
isoflurane	1
)	0
was	0
studied	0
in	0
23	0
adult	0
patients	0
undergoing	0
middle	0
-	0
ear	0
surgery	0
.	0

The	0
mean	0
arterial	0
pressure	0
was	0
decreased	0
from	0
86	0
+	0
/	0
-	0
5	0
(	0
s	0
.	0
e	0
.	0
mean	0
)	0
mmHg	0
to	0
52	0
+	0
/	0
-	0
1	0
mmHg	0
(	0
11	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
7	0
to	0
6	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
1	0
kPa	0
)	0
for	0
98	0
+	0
/	0
-	0
10	0
min	0
in	0
the	0
halothane	1
(	0
H	1
)	0
group	0
,	0
from	0
79	0
+	0
/	0
-	0
5	0
to	0
53	0
+	0
/	0
-	0
1	0
mmHg	0
(	0
10	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
7	0
to	0
7	0
.	0
1	0
+	0
/	0
-	0
0	0
.	0
1	0
kPa	0
)	0
for	0
129	0
+	0
/	0
-	0
11	0
min	0
in	0
the	0
enflurane	1
(	0
E	1
)	0
group	0
,	0
and	0
from	0
80	0
+	0
/	0
-	0
4	0
to	0
49	0
+	0
/	0
-	0
1	0
mmHg	0
(	0
10	0
.	0
7	0
+	0
/	0
-	0
0	0
.	0
5	0
to	0
6	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
1	0
kPa	0
)	0
for	0
135	0
+	0
/	0
-	0
15	0
min	0
in	0
the	0
isoflurane	1
(	0
I	1
)	0
group	0
.	0

The	0
mean	0
H	1
concentration	0
during	0
hypotension	3
in	0
the	0
inspiratory	0
gas	0
was	0
0	0
.	0
7	0
+	0
/	0
-	0
0	0
.	0
1	0
vol	0
%	0
,	0
the	0
mean	0
E	1
concentration	0
1	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
2	0
vol	0
%	0
,	0
and	0
the	0
mean	0
I	1
concentration	0
1	0
.	0
0	0
+	0
/	0
-	0
0	0
.	0
1	0
vol	0
%	0
.	0

In	0
addition	0
,	0
the	0
patients	0
received	0
fentanyl	1
and	0
d	1
-	2
tubocurarine	2
.	0

The	0
initial	0
dose	0
of	0
labetalol	1
for	0
lowering	0
blood	0
pressure	0
was	0
similar	0
,	0
0	0
.	0
52	0
-	0
0	0
.	0
59	0
mg	0
/	0
kg	0
,	0
in	0
all	0
the	0
groups	0
.	0

During	0
hypotension	3
,	0
the	0
heart	0
rate	0
was	0
stable	0
without	0
tachy	3
-	4
or	4
bradycardia	4
.	0

The	0
operating	0
conditions	0
regarding	0
bleeding	3
were	0
estimated	0
in	0
a	0
double	0
-	0
blind	0
manner	0
,	0
and	0
did	0
not	0
differ	0
significantly	0
between	0
the	0
groups	0
.	0

During	0
hypotension	3
,	0
the	0
serum	0
creatinine	1
concentration	0
rose	0
significantly	0
in	0
all	0
groups	0
from	0
the	0
values	0
before	0
hypotension	3
and	0
returned	0
postoperatively	0
to	0
the	0
initial	0
level	0
in	0
the	0
other	0
groups	0
,	0
except	0
the	0
isoflurane	1
group	0
.	0

After	0
hypotension	3
there	0
was	0
no	0
rebound	0
phenomenon	0
in	0
either	0
blood	0
pressure	0
or	0
heart	0
rate	0
.	0

These	0
results	0
indicate	0
that	0
labetalol	1
induces	0
easily	0
adjustable	0
hypotension	3
without	0
compensatory	0
tachycardia	3
and	0
rebound	0
hypertension	3
.	0

Convulsion	3
following	0
intravenous	0
fluorescein	1
angiography	0
.	0

Tonic	3
-	4
clonic	4
seizures	4
followed	0
intravenous	0
fluorescein	1
injection	0
for	0
fundus	0
angiography	0
in	0
a	0
47	0
-	0
year	0
-	0
old	0
male	0
.	0

Despite	0
precautions	0
this	0
adverse	0
reaction	0
recurred	0
on	0
re	0
-	0
exposure	0
to	0
intravenous	0
fluorescein	1
.	0

Pharmacology	0
of	0
ACC	1
-	2
9653	2
(	0
phenytoin	1
prodrug	0
)	0
.	0

ACC	1
-	2
9653	2
,	0
the	0
disodium	1
phosphate	2
ester	2
of	0
3	1
-	2
hydroxymethyl	2
-	2
5	2
,	2
5	2
-	2
diphenylhydantoin	2
,	0
is	0
a	0
prodrug	0
of	0
phenytoin	1
with	0
advantageous	0
physicochemical	0
properties	0
.	0

ACC	1
-	2
9653	2
is	0
rapidly	0
converted	0
enzymatically	0
to	0
phenytoin	1
in	0
vivo	0
.	0

ACC	1
-	2
9653	2
and	0
phenytoin	1
sodium	2
have	0
equivalent	0
anticonvulsant	0
activity	0
against	0
seizures	3
induced	0
by	0
maximal	0
electroshock	0
(	0
MES	0
)	0
in	0
mice	0
following	0
i	0
.	0
p	0
.	0
,	0
oral	0
,	0
or	0
i	0
.	0
v	0
.	0
administration	0
.	0

The	0
ED50	0
doses	0
were	0
16	0
mg	0
/	0
kg	0
for	0
i	0
.	0
v	0
.	0
ACC	1
-	2
9653	2
and	0
8	0
mg	0
/	0
kg	0
for	0
i	0
.	0
v	0
.	0
phenytoin	1
sodium	2
.	0

ACC	1
-	2
9653	2
and	0
phenytoin	1
sodium	2
have	0
similar	0
antiarrhythmic	0
activity	0
against	0
ouabain	1
-	0
induced	0
ventricular	3
tachycardia	4
in	0
anesthetized	0
dogs	0
.	0

The	0
total	0
doses	0
of	0
ACC	1
-	2
9653	2
or	0
phenytoin	1
sodium	2
necessary	0
to	0
convert	0
the	0
arrhythmia	3
to	0
a	0
normal	0
sinus	0
rhythm	0
were	0
24	0
+	0
/	0
-	0
6	0
and	0
14	0
+	0
/	0
-	0
3	0
mg	0
/	0
kg	0
,	0
respectively	0
.	0

0nly	0
phenytoin	1
sodium	2
displayed	0
in	0
vitro	0
antiarrhythmic	0
activity	0
against	0
strophanthidin	1
-	0
induced	0
arrhythmias	3
in	0
guinea	0
pig	0
right	0
atria	0
.	0

In	0
anesthetized	0
dogs	0
,	0
a	0
high	0
dose	0
of	0
ACC	1
-	2
9653	2
(	0
31	0
mg	0
/	0
kg	0
)	0
was	0
infused	0
over	0
15	0
,	0
20	0
,	0
and	0
30	0
min	0
and	0
the	0
responses	0
were	0
compared	0
to	0
an	0
equimolar	0
dose	0
of	0
phenytoin	1
sodium	2
(	0
21	0
mg	0
/	0
kg	0
)	0
.	0

The	0
ACC	1
-	2
9653	2
and	0
phenytoin	1
sodium	2
treatments	0
produced	0
similar	0
marked	0
reductions	0
in	0
diastolic	0
blood	0
pressure	0
and	0
contractile	0
force	0
(	0
LVdP	0
/	0
dt	0
)	0
.	0

The	0
maximum	0
effects	0
of	0
each	0
treatment	0
occurred	0
at	0
the	0
time	0
of	0
maximum	0
phenytoin	1
sodium	2
levels	0
.	0

Acute	0
toxicity	3
studies	0
of	0
ACC	1
-	2
9653	2
and	0
phenytoin	1
sodium	2
were	0
carried	0
out	0
in	0
mice	0
,	0
rats	0
,	0
rabbits	0
,	0
and	0
dogs	0
by	0
i	0
.	0
v	0
.	0
,	0
i	0
.	0
m	0
.	0
,	0
and	0
i	0
.	0
p	0
.	0
routes	0
of	0
administration	0
.	0

The	0
systemic	0
toxic	0
signs	0
of	0
both	0
agents	0
were	0
similar	0
and	0
occurred	0
at	0
approximately	0
equivalent	0
doses	0
.	0

Importantly	0
,	0
the	0
local	0
irritation	0
of	0
ACC	1
-	2
9653	2
was	0
markedly	0
less	0
than	0
phenytoin	1
sodium	2
following	0
i	0
.	0
m	0
.	0
administration	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Tachyphylaxis	0
to	0
systemic	0
but	0
not	0
to	0
airway	0
responses	0
during	0
prolonged	0
therapy	0
with	0
high	0
dose	0
inhaled	0
salbutamol	1
in	0
asthmatics	3
.	0

High	0
doses	0
of	0
inhaled	0
salbutamol	1
produce	0
substantial	0
improvements	0
in	0
airway	0
response	0
in	0
patients	0
with	0
asthma	3
,	0
and	0
are	0
associated	0
with	0
dose	0
-	0
dependent	0
systemic	0
beta	0
-	0
adrenoceptor	0
responses	0
.	0

The	0
purpose	0
of	0
the	0
present	0
study	0
was	0
to	0
investigate	0
whether	0
tachyphylaxis	0
occurs	0
during	0
prolonged	0
treatment	0
with	0
high	0
dose	0
inhaled	0
salbutamol	1
.	0

Twelve	0
asthmatic	3
patients	0
(	0
FEV1	0
,	0
81	0
+	0
/	0
-	0
4	0
%	0
predicted	0
)	0
,	0
requiring	0
only	0
occasional	0
inhaled	0
beta	0
-	0
agonists	0
as	0
their	0
sole	0
therapy	0
,	0
were	0
given	0
a	0
14	0
-	0
day	0
treatment	0
with	0
high	0
dose	0
inhaled	0
salbutamol	1
(	0
HDS	0
)	0
,	0
4	0
,	0
000	0
micrograms	0
daily	0
,	0
low	0
dose	0
inhaled	0
salbutamol	1
(	0
LDS	0
)	0
,	0
800	0
micrograms	0
daily	0
,	0
or	0
placebo	0
(	0
PI	0
)	0
by	0
metered	0
-	0
dose	0
inhaler	0
in	0
a	0
double	0
-	0
blind	0
,	0
randomized	0
crossover	0
design	0
.	0

During	0
the	0
14	0
-	0
day	0
run	0
-	0
in	0
and	0
during	0
washout	0
periods	0
,	0
inhaled	0
beta	0
-	0
agonists	0
were	0
withheld	0
and	0
ipratropium	1
bromide	2
was	0
substituted	0
for	0
rescue	0
purposes	0
.	0

At	0
the	0
end	0
of	0
each	0
14	0
-	0
day	0
treatment	0
,	0
a	0
dose	0
-	0
response	0
curve	0
(	0
DRC	0
)	0
was	0
performed	0
,	0
and	0
airway	0
(	0
FEV1	0
,	0
FEF25	0
-	0
75	0
)	0
chronotropic	0
(	0
HR	0
)	0
,	0
tremor	3
,	0
and	0
metabolic	0
(	0
K	1
,	0
Glu	1
)	0
responses	0
were	0
measured	0
at	0
each	0
step	0
(	0
from	0
100	0
to	0
4	0
,	0
000	0
micrograms	0
)	0
.	0

Treatment	0
had	0
no	0
significant	0
effect	0
on	0
baseline	0
values	0
.	0

There	0
were	0
dose	0
-	0
dependent	0
increases	0
in	0
FEV1	0
and	0
FEF25	0
-	0
75	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
and	0
pretreatment	0
with	0
HDS	0
did	0
not	0
displace	0
the	0
DRC	0
to	0
the	0
right	0
.	0

DRC	0
for	0
HR	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
K	1
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
and	0
Glu	1
(	0
p	0
less	0
than	0
0	0
.	0
005	0
)	0
were	0
attenuated	0
after	0
treatment	0
with	0
HDS	0
compared	0
with	0
PI	0
.	0

There	0
were	0
also	0
differences	0
between	0
HDS	0
and	0
LDS	0
for	0
HR	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
and	0
Glu	1
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
responses	0
.	0

Frequency	0
and	0
severity	0
of	0
subjective	0
adverse	0
effects	0
were	0
also	0
reduced	0
after	0
HDS	0
:	0
tremor	3
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
palpitations	3
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Phenytoin	1
induced	0
fatal	0
hepatic	3
injury	4
.	0

A	0
61	0
year	0
old	0
female	0
developed	0
fatal	0
hepatic	3
failure	4
after	0
phenytoin	1
administration	0
.	0

A	0
typical	0
multisystem	0
clinical	0
pattern	0
precedes	0
the	0
manifestations	0
of	0
hepatic	3
injury	4
.	0

The	0
hematologic	0
,	0
biochemical	0
and	0
pathologic	0
features	0
indicate	0
a	0
mixed	0
hepatocellular	3
damage	4
due	0
to	0
drug	3
hypersensitivity	4
.	0

In	0
a	0
patient	0
receiving	0
phenytoin	1
who	0
presents	0
a	0
viral	0
-	0
like	0
illness	0
,	0
early	0
recognition	0
and	0
discontinuation	0
of	0
the	0
drug	0
are	0
mandatory	0
.	0

Treatment	0
of	0
lethal	0
pertussis	1
vaccine	2
reaction	0
with	0
histamine	1
H1	0
antagonists	0
.	0

We	0
studied	0
mortality	0
after	0
pertussis	3
immunization	0
in	0
the	0
mouse	0
.	0

Without	0
treatment	0
,	0
73	0
of	0
92	0
animals	0
(	0
80	0
%	0
)	0
died	0
after	0
injection	0
of	0
bovine	0
serum	0
albumin	0
(	0
BSA	0
)	0
on	0
day	0
+	0
7	0
of	0
pertussis	3
immunization	0
.	0

After	0
pretreatment	0
with	0
3	0
mg	0
of	0
cyproheptadine	1
,	0
2	0
mg	0
mianserin	1
,	0
or	0
2	0
mg	0
chlorpheniramine	1
,	0
only	0
5	0
of	0
105	0
animals	0
(	0
5	0
%	0
)	0
died	0
after	0
receiving	0
BSA	0
on	0
day	0
+	0
7	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
.	0

Blockade	0
of	0
histamine	1
H1	0
receptors	0
may	0
reduce	0
mortality	0
in	0
pertussis	3
immunization	0
-	0
induced	0
encephalopathy	3
in	0
mice	0
.	0

Support	0
for	0
adrenaline	1
-	0
hypertension	3
hypothesis	0
:	0
18	0
hour	0
pressor	0
effect	0
after	0
6	0
hours	0
adrenaline	1
infusion	0
.	0

In	0
a	0
double	0
blind	0
,	0
crossover	0
study	0
6	0
h	0
infusions	0
of	0
adrenaline	1
(	0
15	0
ng	0
/	0
kg	0
/	0
min	0
;	0
1	0
ng	0
=	0
5	0
.	0
458	0
pmol	0
)	0
,	0
noradrenaline	1
(	0
30	0
ng	0
/	0
kg	0
/	0
min	0
;	0
1	0
ng	0
=	0
5	0
.	0
911	0
pmol	0
)	0
,	0
and	0
a	0
5	0
%	0
dextrose	1
solution	0
(	0
5	0
.	0
4	0
ml	0
/	0
h	0
)	0
,	0
were	0
given	0
to	0
ten	0
healthy	0
volunteers	0
in	0
random	0
order	0
2	0
weeks	0
apart	0
.	0

By	0
means	0
of	0
intra	0
-	0
arterial	0
ambulatory	0
monitoring	0
the	0
haemodynamic	0
effects	0
were	0
followed	0
for	0
18	0
h	0
after	0
the	0
infusions	0
were	0
stopped	0
.	0

Adrenaline	1
,	0
but	0
not	0
noradrenaline	1
,	0
caused	0
a	0
delayed	0
and	0
protracted	0
pressor	0
effect	0
.	0

0ver	0
the	0
total	0
postinfusion	0
period	0
systolic	0
and	0
diastolic	0
arterial	0
pressure	0
were	0
6	0
(	0
SEM	0
2	0
)	0
%	0
and	0
7	0
(	0
2	0
)	0
%	0
,	0
respectively	0
,	0
higher	0
than	0
after	0
dextrose	1
infusion	0
(	0
AN0VA	0
,	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
.	0

Thus	0
,	0
"	0
stress	0
"	0
levels	0
of	0
adrenaline	1
(	0
230	0
pg	0
/	0
ml	0
)	0
for	0
6	0
h	0
cause	0
a	0
delayed	0
and	0
protracted	0
pressor	0
effect	0
.	0

These	0
findings	0
are	0
strong	0
support	0
for	0
the	0
adrenaline	1
-	0
hypertension	3
hypothesis	0
in	0
man	0
.	0

Effect	0
of	0
alkylxanthines	1
on	0
gentamicin	1
-	0
induced	0
acute	3
renal	4
failure	4
in	0
the	0
rat	0
.	0

Adenosine	1
antagonists	0
have	0
been	0
previously	0
shown	0
to	0
be	0
of	0
benefit	0
in	0
some	0
ischaemic	3
and	0
nephrotoxic	3
models	0
of	0
acute	3
renal	4
failure	4
(	0
ARF	3
)	0
.	0

In	0
the	0
present	0
study	0
,	0
the	0
effects	0
of	0
three	0
alkylxanthines	1
with	0
different	0
potencies	0
as	0
adenosine	1
antagonists	0
8	1
-	2
phenyltheophylline	2
,	0
theophylline	1
and	0
enprofylline	1
,	0
were	0
examined	0
in	0
rats	0
developing	0
acute	3
renal	4
failure	4
after	0
4	0
daily	0
injections	0
of	0
gentamicin	1
(	0
200	0
mg	0
kg	0
-	0
1	0
)	0
.	0

Renal	0
function	0
was	0
assessed	0
by	0
biochemical	0
(	0
plasma	0
urea	1
and	0
creatinine	1
)	0
,	0
functional	0
(	0
urine	0
analysis	0
and	0
[	0
3H	0
]	0
inulin	0
and	0
[	0
14C	0
]	0
p	1
-	2
aminohippuric	2
acid	2
clearances	0
)	0
and	0
morphological	0
(	0
degree	0
of	0
necrosis	3
)	0
indices	0
.	0

The	0
various	0
drug	0
treatments	0
produced	0
improvements	0
in	0
some	0
,	0
but	0
not	0
all	0
,	0
measurements	0
of	0
renal	0
function	0
.	0

However	0
,	0
any	0
improvement	0
produced	0
by	0
drug	0
treatment	0
was	0
largely	0
a	0
result	0
of	0
a	0
beneficial	0
effect	0
exerted	0
by	0
its	0
vehicle	0
(	0
polyethylene	1
glycol	2
and	0
Na0H	1
)	0
.	0

The	0
lack	0
of	0
any	0
consistent	0
protective	0
effect	0
noted	0
with	0
the	0
alkylxanthines	1
tested	0
in	0
the	0
present	0
study	0
indicates	0
that	0
adenosine	1
plays	0
little	0
,	0
if	0
any	0
,	0
pathophysiological	0
role	0
in	0
gentamicin	1
-	0
induced	0
ARF	3
.	0

Adverse	0
ocular	0
reactions	0
possibly	0
associated	0
with	0
isotretinoin	1
.	0

A	0
total	0
of	0
261	0
adverse	0
ocular	0
reactions	0
occurred	0
in	0
237	0
patients	0
who	0
received	0
isotretinoin	1
,	0
a	0
commonly	0
used	0
drug	0
in	0
the	0
treatment	0
of	0
severe	0
cystic	0
acne	3
.	0

Blepharoconjunctivitis	3
,	0
subjective	0
complaints	0
of	0
dry	3
eyes	4
,	0
blurred	3
vision	4
,	0
contact	0
lens	0
intolerance	0
,	0
and	0
photodermatitis	3
are	0
reversible	0
side	0
effects	0
.	0

More	0
serious	0
ocular	0
adverse	0
reactions	0
include	0
papilledema	3
,	0
pseudotumor	3
cerebri	4
,	0
and	0
white	0
or	0
gray	0
subepithelial	0
corneal	3
opacities	4
;	0
all	0
of	0
these	0
are	0
reversible	0
if	0
the	0
drug	0
is	0
discontinued	0
.	0

Reported	0
cases	0
of	0
decreased	0
dark	0
adaptation	0
are	0
under	0
investigation	0
.	0

Isotretinoin	1
is	0
contraindicated	0
in	0
pregnancy	0
because	0
of	0
the	0
many	0
reported	0
congenital	3
abnormalities	4
after	0
maternal	0
use	0
(	0
including	0
microphthalmos	3
,	0
orbital	0
hypertelorism	3
,	0
and	0
optic	3
nerve	4
hypoplasia	4
)	0
.	0

Procaterol	1
and	0
terbutaline	1
in	0
bronchial	3
asthma	4
.	0

A	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
,	0
cross	0
-	0
over	0
study	0
.	0

Procaterol	1
,	0
a	0
new	0
beta	0
-	0
2	0
adrenoceptor	0
stimulant	0
,	0
was	0
studied	0
in	0
a	0
double	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
,	0
cross	0
-	0
over	0
trial	0
in	0
patients	0
with	0
bronchial	3
asthma	4
.	0

0ral	0
procaterol	1
50	0
micrograms	0
b	0
.	0
d	0
.	0
,	0
procaterol	1
100	0
micrograms	0
b	0
.	0
d	0
.	0
,	0
and	0
terbutaline	1
5	0
mg	0
t	0
.	0
i	0
.	0
d	0
.	0
,	0
were	0
compared	0
when	0
given	0
randomly	0
in	0
1	0
-	0
week	0
treatment	0
periods	0
.	0

The	0
best	0
clinical	0
effect	0
was	0
found	0
with	0
terbutaline	1
.	0

Both	0
anti	0
-	0
asthmatic	3
and	0
tremorgenic	3
effects	0
of	0
procaterol	1
were	0
dose	0
-	0
related	0
.	0

Procaterol	1
appeared	0
effective	0
in	0
the	0
doses	0
tested	0
,	0
and	0
a	0
twice	0
daily	0
regimen	0
would	0
appear	0
to	0
be	0
suitable	0
with	0
this	0
drug	0
.	0

Subacute	0
effects	0
of	0
propranolol	1
and	0
B	0
24	0
/	0
76	0
on	0
isoproterenol	1
-	0
induced	0
rat	0
heart	3
hypertrophy	4
in	0
correlation	0
with	0
blood	0
pressure	0
.	0

We	0
compared	0
the	0
potential	0
beta	0
-	0
receptor	0
blocker	0
,	0
B	0
24	0
/	0
76	0
i	0
.	0
e	0
.	0
1	0
-	0
(	0
2	0
,	0
4	0
-	0
dichlorophenoxy	0
)	0
-	0
3	0
[	0
2	0
-	0
3	0
,	0
4	0
-	0
dimethoxyphenyl	0
)	0
ethanolamino	0
]	0
-	0
prop	0
an	0
-	0
2	0
-	0
ol	0
,	0
which	0
is	0
characterized	0
by	0
beta	0
1	0
-	0
adrenoceptor	0
blocking	0
and	0
beta	0
2	0
-	0
adrenoceptor	0
stimulating	0
properties	0
with	0
propranolol	1
.	0

The	0
studies	0
were	0
performed	0
using	0
an	0
experimental	0
model	0
of	0
isoproterenol	1
-	0
induced	0
heart	3
hypertrophy	4
in	0
rats	0
.	0

A	0
correlation	0
of	0
the	0
blood	0
pressure	0
was	0
neither	0
found	0
in	0
the	0
development	0
nor	0
in	0
the	0
attempt	0
to	0
suppress	0
the	0
development	0
of	0
heart	3
hypertrophy	4
with	0
the	0
two	0
beta	0
-	0
receptor	0
blockers	0
.	0

Both	0
beta	0
-	0
blockers	0
influenced	0
the	0
development	0
of	0
hypertrophy	3
to	0
a	0
different	0
,	0
but	0
not	0
reproducible	0
extent	0
.	0

It	0
was	0
possible	0
to	0
suppress	0
the	0
increased	0
ornithine	1
decarboxylase	0
activity	0
with	0
both	0
beta	0
-	0
blockers	0
in	0
hypertrophied	3
hearts	4
,	0
but	0
there	0
was	0
no	0
effect	0
on	0
the	0
heart	0
mass	0
.	0

Neither	0
propranolol	1
nor	0
B	0
24	0
/	0
76	0
could	0
stop	0
the	0
changes	0
in	0
the	0
characteristic	0
myosin	0
isoenzyme	0
pattern	0
of	0
the	0
hypertrophied	3
rat	0
heart	0
.	0

Thus	0
,	0
the	0
investigations	0
did	0
not	0
provide	0
any	0
evidence	0
that	0
the	0
beta	0
-	0
receptor	0
blockers	0
propranolol	1
and	0
B	0
24	0
/	0
76	0
have	0
the	0
potency	0
to	0
prevent	0
isoproterenol	1
from	0
producing	0
heart	3
hypertrophy	4
.	0

Increased	0
anxiogenic	0
effects	0
of	0
caffeine	1
in	0
panic	3
disorders	4
.	0

The	0
effects	0
of	0
oral	0
administration	0
of	0
caffeine	1
(	0
10	0
mg	0
/	0
kg	0
)	0
on	0
behavioral	0
ratings	0
,	0
somatic	0
symptoms	0
,	0
blood	0
pressure	0
and	0
plasma	0
levels	0
of	0
3	1
-	2
methoxy	2
-	2
4	2
-	2
hydroxyphenethyleneglycol	2
(	0
MHPG	1
)	0
and	0
cortisol	1
were	0
determined	0
in	0
17	0
healthy	0
subjects	0
and	0
21	0
patients	0
meeting	0
DSM	0
-	0
III	0
criteria	0
for	0
agoraphobia	3
with	0
panic	3
attacks	4
or	0
panic	3
disorder	4
.	0

Caffeine	1
produced	0
significantly	0
greater	0
increases	0
in	0
subject	0
-	0
rated	0
anxiety	3
,	0
nervousness	0
,	0
fear	0
,	0
nausea	3
,	0
palpitations	3
,	0
restlessness	3
,	0
and	0
tremors	3
in	0
the	0
patients	0
compared	0
with	0
healthy	0
subjects	0
.	0

In	0
the	0
patients	0
,	0
but	0
not	0
the	0
healthy	0
subjects	0
,	0
these	0
symptoms	0
were	0
significantly	0
correlated	0
with	0
plasma	0
caffeine	1
levels	0
.	0

Seventy	0
-	0
one	0
percent	0
of	0
the	0
patients	0
reported	0
that	0
the	0
behavioral	0
effects	0
of	0
caffeine	1
were	0
similar	0
to	0
those	0
experienced	0
during	0
panic	3
attacks	4
.	0

Caffeine	1
did	0
not	0
alter	0
plasma	0
MHPG	1
levels	0
in	0
either	0
the	0
healthy	0
subjects	0
or	0
patients	0
.	0

Caffeine	1
increased	0
plasma	0
cortisol	1
levels	0
equally	0
in	0
the	0
patient	0
and	0
healthy	0
groups	0
.	0

Because	0
caffeine	1
is	0
an	0
adenosine	1
receptor	0
antagonist	0
,	0
these	0
results	0
suggest	0
that	0
some	0
panic	3
disorder	4
patients	0
may	0
have	0
abnormalities	3
in	4
neuronal	4
systems	4
involving	0
adenosine	1
.	0

Patients	0
with	0
anxiety	3
disorders	4
may	0
benefit	0
by	0
avoiding	0
caffeine	1
-	0
containing	0
foods	0
and	0
beverages	0
.	0

Comparison	0
of	0
the	0
effect	0
of	0
oxitropium	1
bromide	2
and	0
of	0
slow	0
-	0
release	0
theophylline	1
on	0
nocturnal	0
asthma	3
.	0

The	0
effects	0
of	0
a	0
new	0
inhaled	0
antimuscarinic	0
drug	0
,	0
oxitropium	1
bromide	2
,	0
and	0
of	0
a	0
slow	0
-	0
release	0
theophylline	1
preparation	0
upon	0
nocturnal	0
asthma	3
were	0
compared	0
in	0
a	0
placebo	0
-	0
controlled	0
double	0
-	0
blind	0
study	0
.	0

Two	0
samples	0
were	0
studied	0
:	0
12	0
patients	0
received	0
oxitropium	1
at	0
600	0
micrograms	0
(	0
6	0
subjects	0
)	0
or	0
at	0
400	0
micrograms	0
t	0
.	0
i	0
.	0
d	0
.	0

(	0
6	0
subjects	0
)	0
whereas	0
11	0
received	0
theophylline	1
at	0
300	0
mg	0
b	0
.	0
i	0
.	0
d	0
.	0

Morning	0
dipping	0
,	0
assessed	0
by	0
the	0
fall	0
in	0
peak	0
flow	0
overnight	0
,	0
was	0
significantly	0
reduced	0
in	0
the	0
periods	0
when	0
either	0
active	0
drug	0
was	0
taken	0
,	0
whereas	0
no	0
difference	0
was	0
noticed	0
during	0
the	0
placebo	0
administration	0
.	0

No	0
significant	0
difference	0
was	0
noticed	0
between	0
results	0
obtained	0
with	0
either	0
active	0
drug	0
,	0
as	0
well	0
as	0
with	0
either	0
dosage	0
of	0
oxitropium	1
.	0

No	0
subject	0
reported	0
side	0
effects	0
of	0
oxitropium	1
,	0
as	0
compared	0
to	0
three	0
subjects	0
reporting	0
nausea	3
,	0
vomiting	3
and	0
tremors	3
after	0
theophylline	1
.	0

0xitropium	1
proves	0
to	0
be	0
a	0
valuable	0
alternative	0
to	0
theophylline	1
in	0
nocturnal	0
asthma	3
,	0
since	0
it	0
is	0
equally	0
potent	0
,	0
safer	0
and	0
does	0
not	0
require	0
the	0
titration	0
of	0
dosage	0
.	0

Penicillin	1
anaphylaxis	3
.	0

A	0
case	0
of	0
oral	0
penicillin	1
anaphylaxis	3
is	0
described	0
,	0
and	0
the	0
terminology	0
,	0
occurrence	0
,	0
clinical	0
manifestations	0
,	0
pathogenesis	0
,	0
prevention	0
,	0
and	0
treatment	0
of	0
anaphylaxis	3
are	0
reviewed	0
.	0

Emergency	0
physicians	0
should	0
be	0
aware	0
of	0
oral	0
penicillin	1
anaphylaxis	3
in	0
order	0
to	0
prevent	0
its	0
occurrence	0
by	0
prescribing	0
the	0
antibiotic	0
judiciously	0
and	0
knowledgeably	0
and	0
to	0
offer	0
optimal	0
medical	0
therapy	0
once	0
this	0
life	0
-	0
threatening	0
reaction	0
has	0
begun	0
.	0

Reversible	0
valproic	1
acid	2
-	0
induced	0
dementia	3
:	0
a	0
case	0
report	0
.	0

Reversible	0
valproic	1
acid	2
-	0
induced	0
dementia	3
was	0
documented	0
in	0
a	0
21	0
-	0
year	0
-	0
old	0
man	0
with	0
epilepsy	3
who	0
had	0
a	0
3	0
-	0
year	0
history	0
of	0
insidious	0
progressive	0
decline	0
in	0
global	0
cognitive	0
abilities	0
documented	0
by	0
serial	0
neuropsychological	0
studies	0
.	0

Repeat	0
neuropsychological	0
testing	0
7	0
weeks	0
after	0
discontinuation	0
of	0
the	0
drug	0
revealed	0
dramatic	0
improvement	0
in	0
IQ	0
,	0
memory	0
,	0
naming	0
,	0
and	0
other	0
tasks	0
commensurate	0
with	0
clinical	0
recovery	0
in	0
his	0
intellectual	0
capacity	0
.	0

Possible	0
pathophysiological	0
mechanisms	0
which	0
may	0
have	0
been	0
operative	0
in	0
this	0
case	0
include	0
:	0
a	0
direct	0
central	0
nervous	0
system	0
(	0
CNS	0
)	0
toxic	0
effect	0
of	0
valproic	1
acid	2
;	0
a	0
paradoxical	0
epileptogenic	0
effect	0
secondary	0
to	0
the	0
drug	0
;	0
and	0
an	0
indirect	0
CNS	0
toxic	0
effect	0
mediated	0
through	0
valproic	1
acid	2
-	0
induced	0
hyperammonemia	3
.	0

Reversal	0
of	0
scopolamine	1
-	0
induced	0
amnesia	3
of	0
passive	0
avoidance	0
by	0
pre	0
-	0
and	0
post	0
-	0
training	0
naloxone	1
.	0

In	0
a	0
series	0
of	0
five	0
experiments	0
,	0
the	0
modulating	0
role	0
of	0
naloxone	1
on	0
a	0
scopolamine	1
-	0
induced	0
retention	3
deficit	4
in	0
a	0
passive	0
avoidance	0
paradigm	0
was	0
investigated	0
in	0
mice	0
.	0

Scopolamine	1
,	0
but	0
not	0
methyl	1
scopolamine	2
(	0
1	0
and	0
3	0
mg	0
/	0
kg	0
)	0
,	0
induced	0
an	0
amnesia	3
as	0
measured	0
by	0
latency	0
and	0
duration	0
parameters	0
.	0

Naloxone	1
(	0
0	0
.	0
3	0
,	0
1	0
,	0
3	0
,	0
and	0
10	0
mg	0
/	0
kg	0
)	0
injected	0
prior	0
to	0
training	0
attenuated	0
the	0
retention	3
deficit	4
with	0
a	0
peak	0
of	0
activity	0
at	0
3	0
mg	0
/	0
kg	0
.	0

The	0
effect	0
of	0
naloxone	1
could	0
be	0
antagonized	0
with	0
morphine	1
(	0
1	0
,	0
3	0
,	0
and	0
10	0
mg	0
/	0
kg	0
)	0
,	0
demonstrating	0
the	0
opioid	0
specificity	0
of	0
the	0
naloxone	1
effect	0
.	0

Post	0
-	0
training	0
administration	0
of	0
naloxone	1
(	0
3	0
mg	0
/	0
kg	0
)	0
as	0
a	0
single	0
or	0
as	0
a	0
split	0
dose	0
also	0
attenuated	0
the	0
scopolamine	1
-	0
induced	0
amnesia	3
.	0

Control	0
experiments	0
indicated	0
that	0
neither	0
an	0
increase	0
in	0
pain	3
sensitivity	0
(	0
pre	0
-	0
training	0
naloxone	1
)	0
nor	0
an	0
induced	0
aversive	0
state	0
(	0
post	0
-	0
training	0
naloxone	1
)	0
appear	0
to	0
be	0
responsible	0
for	0
the	0
influence	0
of	0
naloxone	1
on	0
the	0
scopolamine	1
-	0
induced	0
retention	3
deficit	4
.	0

These	0
results	0
extend	0
previous	0
findings	0
implicating	0
a	0
cholinergic	0
-	0
opioid	0
interaction	0
in	0
memory	0
processes	0
.	0

A	0
possible	0
mechanism	0
for	0
this	0
interaction	0
involving	0
the	0
septo	0
-	0
hippocampal	0
cholinergic	0
pathway	0
is	0
discussed	0
.	0

Electron	0
microscopic	0
investigations	0
of	0
the	0
cyclophosphamide	1
-	0
induced	0
lesions	3
of	4
the	4
urinary	4
bladder	4
of	0
the	0
rat	0
and	0
their	0
prevention	0
by	0
mesna	1
.	0

Fully	0
developed	0
cyclophosphamide	1
-	0
induced	0
cystitis	3
is	0
characterized	0
by	0
nearly	0
complete	0
detachment	0
of	0
the	0
urothelium	0
,	0
severe	0
submucosal	0
edema	3
owing	0
to	0
damage	0
to	0
the	0
microvascular	0
bed	0
and	0
focal	0
muscle	0
necroses	3
.	0

The	0
initial	0
response	0
to	0
the	0
primary	0
attack	0
by	0
the	0
cyclophosphamide	1
metabolites	0
seems	0
to	0
be	0
fragmentation	0
of	0
the	0
luminal	1
membrane	0
.	0

This	0
damages	0
the	0
cellular	0
barrier	0
against	0
the	0
hypertonic	0
urine	0
.	0

Subsequent	0
breaks	0
in	0
the	0
lateral	0
cell	0
membranes	0
of	0
the	0
superficial	0
cells	0
and	0
in	0
all	0
the	0
plasma	0
membranes	0
of	0
the	0
intermediate	0
and	0
basal	0
cells	0
,	0
intercellular	0
and	0
intracellular	0
edema	3
and	0
disintegration	0
of	0
the	0
desmosomes	0
and	0
hemidesmosomes	0
lead	0
to	0
progressive	0
degeneration	0
and	0
detachment	0
of	0
the	0
epithelial	0
cells	0
with	0
exposure	0
and	0
splitting	0
of	0
the	0
basal	0
membrane	0
.	0

The	0
morphological	0
changes	0
of	0
the	0
endothelial	0
cells	0
,	0
which	0
become	0
more	0
pronounced	0
in	0
the	0
later	0
stages	0
of	0
the	0
experiment	0
,	0
the	0
involvement	0
of	0
blood	0
vessels	0
regardless	0
of	0
their	0
diameter	0
and	0
the	0
location	0
-	0
dependent	0
extent	0
of	0
the	0
damage	0
indicate	0
a	0
direct	0
type	0
of	0
damage	0
which	0
is	0
preceded	0
by	0
a	0
mediator	0
-	0
induced	0
increase	0
in	0
permeability	0
,	0
the	0
morphological	0
correlate	0
of	0
which	0
is	0
the	0
formation	0
of	0
gaps	0
in	0
the	0
interendothelial	0
cell	0
connections	0
on	0
the	0
venules	0
.	0

These	0
changes	0
can	0
be	0
effectively	0
prevented	0
by	0
mesna	1
.	0

The	0
only	0
sign	0
of	0
a	0
possible	0
involvement	0
is	0
the	0
increase	0
in	0
the	0
number	0
of	0
specific	0
granules	0
with	0
a	0
presumed	0
lysosomal	0
function	0
in	0
the	0
superficial	0
cells	0
.	0

Increase	0
in	0
intragastric	0
pressure	0
during	0
suxamethonium	1
-	0
induced	0
muscle	3
fasciculations	4
in	0
children	0
:	0
inhibition	0
by	0
alfentanil	1
.	0

Changes	0
in	0
intragastric	0
pressure	0
after	0
the	0
administration	0
of	0
suxamethonium	1
1	0
.	0
5	0
mg	0
kg	0
-	0
1	0
i	0
.	0
v	0
.	0
were	0
studied	0
in	0
32	0
children	0
(	0
mean	0
age	0
6	0
.	0
9	0
yr	0
)	0
pretreated	0
with	0
either	0
physiological	0
saline	0
or	0
alfentanil	1
50	0
micrograms	0
kg	0
-	0
1	0
.	0

Anaesthesia	0
was	0
induced	0
with	0
thiopentone	1
5	0
mg	0
kg	0
-	0
1	0
.	0

The	0
incidence	0
and	0
intensity	0
of	0
muscle	3
fasciculations	4
caused	0
by	0
suxamethonium	1
were	0
significantly	0
greater	0
in	0
the	0
control	0
than	0
in	0
the	0
alfentanil	1
group	0
.	0

The	0
intragastric	0
pressure	0
during	0
muscle	3
fasciculations	4
was	0
significantly	0
higher	0
in	0
the	0
control	0
group	0
(	0
16	0
+	0
/	0
-	0
0	0
.	0
7	0
(	0
SEM	0
)	0
cm	0
H20	1
)	0
than	0
in	0
the	0
alfentanil	1
group	0
(	0
7	0
.	0
7	0
+	0
/	0
-	0
1	0
.	0
5	0
(	0
SEM	0
)	0
cm	0
H20	1
)	0
.	0

The	0
increase	0
in	0
intragastric	0
pressure	0
was	0
directly	0
related	0
to	0
the	0
intensity	0
of	0
muscle	3
fasciculations	4
(	0
regression	0
line	0
:	0
y	0
=	0
0	0
.	0
5	0
+	0
4	0
.	0
78x	0
with	0
r	0
of	0
0	0
.	0
78	0
)	0
.	0

It	0
is	0
concluded	0
that	0
intragastric	0
pressure	0
increases	0
significantly	0
during	0
muscle	3
fasciculations	4
caused	0
by	0
suxamethonium	1
in	0
healthy	0
children	0
.	0

Alfentanil	1
50	0
micrograms	0
kg	0
-	0
1	0
effectively	0
inhibits	0
the	0
incidence	0
and	0
intensity	0
of	0
suxamethonium	1
-	0
induced	0
muscle	3
fasciculations	4
;	0
moreover	0
,	0
intragastric	0
pressure	0
remains	0
at	0
its	0
control	0
value	0
.	0

Acute	0
insulin	0
treatment	0
normalizes	0
the	0
resistance	0
to	0
the	0
cardiotoxic	3
effect	0
of	0
isoproterenol	1
in	0
streptozotocin	1
diabetic	3
rats	0
.	0

A	0
morphometric	0
study	0
of	0
isoproterenol	1
induced	0
myocardial	0
fibrosis	3
.	0

The	0
acute	0
effect	0
of	0
insulin	0
treatment	0
on	0
the	0
earlier	0
reported	0
protective	0
effect	0
of	0
streptozotocin	1
diabetes	3
against	0
the	0
cardiotoxic	3
effect	0
of	0
high	0
doses	0
of	0
isoproterenol	1
(	0
IS0	1
)	0
was	0
investigated	0
in	0
rats	0
.	0

Thirty	0
to	0
135	0
min	0
after	0
the	0
injection	0
of	0
crystalline	0
insulin	0
,	0
IS0	1
was	0
given	0
subcutaneously	0
and	0
when	0
IS0	1
induced	0
fibrosis	3
in	0
the	0
myocardium	0
was	0
morphometrically	0
analyzed	0
7	0
days	0
later	0
,	0
a	0
highly	0
significant	0
correlation	0
(	0
r	0
=	0
0	0
.	0
83	0
,	0
2	0
p	0
=	0
0	0
.	0
006	0
)	0
to	0
the	0
slope	0
of	0
the	0
fall	0
in	0
blood	0
glucose	1
after	0
insulin	0
treatment	0
appeared	0
.	0

The	0
myocardial	0
content	0
of	0
catecholamines	1
was	0
estimated	0
in	0
these	0
8	0
day	0
diabetic	3
rats	0
.	0

The	0
norepinephrine	1
content	0
was	0
significantly	0
increased	0
while	0
epinephrine	1
remained	0
unchanged	0
.	0

An	0
enhanced	0
sympathetic	0
nervous	0
system	0
activity	0
with	0
a	0
consequent	0
down	0
regulation	0
of	0
the	0
myocardial	0
beta	0
-	0
adrenergic	0
receptors	0
could	0
,	0
therefore	0
,	0
explain	0
this	0
catecholamine	1
resistance	0
.	0

The	0
rapid	0
reversion	0
after	0
insulin	0
treatment	0
excludes	0
the	0
possibility	0
that	0
streptozotocin	1
in	0
itself	0
causes	0
the	0
IS0	1
resistance	0
and	0
points	0
towards	0
a	0
direct	0
insulin	0
effect	0
on	0
myocardial	0
catecholamine	1
sensitivity	0
in	0
diabetic	3
rats	0
.	0

The	0
phenomenon	0
described	0
might	0
elucidate	0
pathogenetic	0
mechanisms	0
behind	0
toxic	0
myocardial	0
cell	0
degeneration	0
and	0
may	0
possibly	0
have	0
relevance	0
for	0
acute	0
cardiovascular	0
complications	0
in	0
diabetic	3
patients	0
.	0

Differential	0
effects	0
of	0
non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
drugs	0
on	0
seizures	3
produced	0
by	0
pilocarpine	1
in	0
rats	0
.	0

The	0
muscarinic	0
cholinergic	0
agonist	0
pilocarpine	1
induces	0
in	0
rats	0
seizures	3
and	0
status	3
epilepticus	4
followed	0
by	0
widespread	0
damage	0
to	0
the	0
forebrain	0
.	0

The	0
present	0
study	0
was	0
designed	0
to	0
investigate	0
the	0
effect	0
of	0
5	0
non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
drugs	0
,	0
sodium	1
salicylate	2
,	0
phenylbutazone	1
,	0
indomethacin	1
,	0
ibuprofen	1
and	0
mefenamic	1
acid	2
,	0
on	0
seizures	3
produced	0
by	0
pilocarpine	1
.	0

Pretreatment	0
of	0
rats	0
with	0
sodium	1
salicylate	2
,	0
ED50	0
103	0
mg	0
/	0
kg	0
(	0
60	0
-	0
174	0
)	0
,	0
and	0
phenylbutazone	1
,	0
59	0
mg	0
/	0
kg	0
(	0
50	0
-	0
70	0
)	0
converted	0
the	0
non	0
-	0
convulsant	0
dose	0
of	0
pilocarpine	1
,	0
200	0
mg	0
/	0
kg	0
,	0
to	0
a	0
convulsant	0
one	0
.	0

Indomethacin	1
,	0
1	0
-	0
10	0
mg	0
/	0
kg	0
,	0
and	0
ibuprofen	1
,	0
10	0
-	0
100	0
mg	0
/	0
kg	0
,	0
failed	0
to	0
modulate	0
seizures	3
produced	0
by	0
pilocarpine	1
.	0

Mefenamic	1
acid	2
,	0
26	0
(	0
22	0
-	0
30	0
)	0
mg	0
/	0
kg	0
,	0
prevented	0
seizures	3
and	0
protected	0
rats	0
from	0
seizure	3
-	0
related	0
brain	3
damage	4
induced	0
by	0
pilocarpine	1
,	0
380	0
mg	0
/	0
kg	0
.	0

These	0
results	0
indicate	0
that	0
non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
drugs	0
differentially	0
modulate	0
the	0
threshold	0
for	0
pilocarpine	1
-	0
induced	0
seizures	3
.	0

Acute	3
neurologic	4
dysfunction	4
after	0
high	0
-	0
dose	0
etoposide	1
therapy	0
for	0
malignant	3
glioma	4
.	0

Etoposide	1
(	0
VP	1
-	2
16	2
-	2
213	2
)	0
has	0
been	0
used	0
in	0
the	0
treatment	0
of	0
many	0
solid	0
tumors	3
and	0
hematologic	3
malignancies	4
.	0

When	0
used	0
in	0
high	0
doses	0
and	0
in	0
conjunction	0
with	0
autologous	0
bone	0
marrow	0
transplantation	0
,	0
this	0
agent	0
has	0
activity	0
against	0
several	0
treatment	0
-	0
resistant	0
cancers	3
including	0
malignant	3
glioma	4
.	0

In	0
six	0
of	0
eight	0
patients	0
(	0
75	0
%	0
)	0
who	0
we	0
treated	0
for	0
recurrent	0
or	0
resistant	0
glioma	3
,	0
sudden	0
severe	0
neurologic	3
deterioration	4
occurred	0
.	0

This	0
developed	0
a	0
median	0
of	0
9	0
days	0
after	0
initiation	0
of	0
high	0
-	0
dose	0
etoposide	1
therapy	0
.	0

Significant	0
clinical	0
manifestations	0
have	0
included	0
confusion	3
,	0
papilledema	3
,	0
somnolence	3
,	0
exacerbation	0
of	0
motor	3
deficits	4
,	0
and	0
sharp	0
increase	0
in	0
seizure	3
activity	0
.	0

These	0
abnormalities	0
resolved	0
rapidly	0
after	0
initiation	0
of	0
high	0
-	0
dose	0
intravenous	0
dexamethasone	1
therapy	0
.	0

In	0
all	0
patients	0
,	0
computerized	0
tomographic	0
(	0
CT	0
)	0
brain	0
scans	0
demonstrated	0
stability	0
in	0
tumor	3
size	0
and	0
peritumor	0
edema	3
when	0
compared	0
with	0
pretransplant	0
scans	0
.	0

This	0
complication	0
appears	0
to	0
represent	0
a	0
significant	0
new	0
toxicity	3
of	0
high	0
-	0
dose	0
etoposide	1
therapy	0
for	0
malignant	3
glioma	4
.	0

Progressive	0
bile	3
duct	4
injury	4
after	0
thiabendazole	1
administration	0
.	0

A	0
27	0
-	0
yr	0
-	0
old	0
man	0
developed	0
jaundice	3
2	0
wk	0
after	0
exposure	0
to	0
thiabendazole	1
.	0

Cholestasis	3
persisted	0
for	0
3	0
yr	0
,	0
at	0
which	0
time	0
a	0
liver	0
transplant	0
was	0
performed	0
.	0

Two	0
liver	0
biopsy	0
specimens	0
and	0
the	0
hepatectomy	0
specimen	0
were	0
remarkable	0
for	0
almost	0
complete	0
disappearance	0
of	0
interlobular	0
bile	0
ducts	0
.	0

Prominent	0
fibrosis	3
and	0
hepatocellular	0
regeneration	0
were	0
also	0
present	0
;	0
however	0
,	0
the	0
lobular	0
architecture	0
was	0
preserved	0
.	0

This	0
case	0
represents	0
an	0
example	0
of	0
"	0
idiosyncratic	0
"	0
drug	3
-	4
induced	4
liver	4
damage	4
in	0
which	0
the	0
primary	0
target	0
of	0
injury	0
is	0
the	0
bile	0
duct	0
.	0

An	0
autoimmune	0
pathogenesis	0
of	0
the	0
bile	3
duct	4
destruction	4
is	0
suggested	0
.	0

Differential	0
effects	0
of	0
1	1
,	2
4	2
-	2
dihydropyridine	2
calcium	1
channel	2
blockers	2
:	0
therapeutic	0
implications	0
.	0

Increasing	0
recognition	0
of	0
the	0
importance	0
of	0
calcium	1
in	0
the	0
pathogenesis	0
of	0
cardiovascular	3
disease	4
has	0
stimulated	0
research	0
into	0
the	0
use	0
of	0
calcium	1
channel	2
blocking	2
agents	2
for	0
treatment	0
of	0
a	0
variety	0
of	0
cardiovascular	3
diseases	4
.	0

The	0
favorable	0
efficacy	0
and	0
tolerability	0
profiles	0
of	0
these	0
agents	0
make	0
them	0
attractive	0
therapeutic	0
modalities	0
.	0

Clinical	0
applications	0
of	0
calcium	1
channel	2
blockers	2
parallel	0
their	0
tissue	0
selectivity	0
.	0

In	0
contrast	0
to	0
verapamil	1
and	0
diltiazem	1
,	0
which	0
are	0
roughly	0
equipotent	0
in	0
their	0
actions	0
on	0
the	0
heart	0
and	0
vascular	0
smooth	0
muscle	0
,	0
the	0
dihydropyridine	1
calcium	1
channel	2
blockers	2
are	0
a	0
group	0
of	0
potent	0
peripheral	0
vasodilator	0
agents	0
that	0
exert	0
minimal	0
electrophysiologic	0
effects	0
on	0
cardiac	0
nodal	0
or	0
conduction	0
tissue	0
.	0

As	0
the	0
first	0
dihydropyridine	1
available	0
for	0
use	0
in	0
the	0
United	0
States	0
,	0
nifedipine	1
controls	0
angina	3
and	0
hypertension	3
with	0
minimal	0
depression	0
of	0
cardiac	0
function	0
.	0

Additional	0
members	0
of	0
this	0
group	0
of	0
calcium	1
channel	2
blockers	2
have	0
been	0
studied	0
for	0
a	0
variety	0
of	0
indications	0
for	0
which	0
they	0
may	0
offer	0
advantages	0
over	0
current	0
therapy	0
.	0

0nce	0
or	0
twice	0
daily	0
dosage	0
possible	0
with	0
nitrendipine	1
and	0
nisoldipine	1
offers	0
a	0
convenient	0
administration	0
schedule	0
,	0
which	0
encourages	0
patient	0
compliance	0
in	0
long	0
-	0
term	0
therapy	0
of	0
hypertension	3
.	0

The	0
coronary	0
vasodilating	0
properties	0
of	0
nisoldipine	1
have	0
led	0
to	0
the	0
investigation	0
of	0
this	0
agent	0
for	0
use	0
in	0
angina	3
.	0

Selectivity	0
for	0
the	0
cerebrovascular	0
bed	0
makes	0
nimodipine	1
potentially	0
useful	0
in	0
the	0
treatment	0
of	0
subarachnoid	3
hemorrhage	4
,	0
migraine	3
headache	4
,	0
dementia	3
,	0
and	0
stroke	3
.	0

In	0
general	0
,	0
the	0
dihydropyridine	1
calcium	1
channel	2
blockers	2
are	0
usually	0
well	0
tolerated	0
,	0
with	0
headache	3
,	0
facial	0
flushing	3
,	0
palpitations	3
,	0
edema	3
,	0
nausea	3
,	0
anorexia	3
,	0
and	0
dizziness	3
being	0
the	0
more	0
common	0
adverse	0
effects	0
.	0

The	0
enhancement	0
of	0
aminonucleoside	1
nephrosis	3
by	0
the	0
co	0
-	0
administration	0
of	0
protamine	0
.	0

An	0
experimental	0
model	0
of	0
focal	3
segmental	4
glomerular	4
sclerosis	4
(	0
FSGS	3
)	0
was	0
developed	0
in	0
rats	0
by	0
the	0
combined	0
administration	0
of	0
puromycin	1
-	2
aminonucleoside	2
(	0
AMNS	1
)	0
and	0
protamine	1
sulfate	2
(	0
PS	1
)	0
.	0

Male	0
Sprague	0
-	0
Dawley	0
rats	0
,	0
uninephrectomized	0
three	0
weeks	0
before	0
,	0
received	0
daily	0
injections	0
of	0
subcutaneous	0
AMNS	1
(	0
1	0
mg	0
/	0
100	0
g	0
body	0
wt	0
)	0
and	0
intravenous	0
PS	1
(	0
2	0
separated	0
doses	0
of	0
2	0
.	0
5	0
mg	0
/	0
100	0
g	0
body	0
wt	0
)	0
for	0
four	0
days	0
.	0

The	0
series	0
of	0
injections	0
were	0
repeated	0
another	0
three	0
times	0
at	0
10	0
day	0
intervals	0
.	0

The	0
animals	0
were	0
sacrificed	0
on	0
days	0
24	0
,	0
52	0
,	0
and	0
80	0
.	0

They	0
developed	0
nephrotic	3
syndrome	4
and	0
finally	0
renal	3
failure	4
.	0

The	0
time	0
-	0
course	0
curve	0
of	0
creatinine	1
clearance	0
dropped	0
and	0
showed	0
significant	0
difference	0
(	0
P	0
less	0
than	0
0	0
.	0
01	0
)	0
from	0
that	0
of	0
each	0
control	0
group	0
,	0
such	0
as	0
,	0
AMNS	1
alone	0
,	0
PS	1
alone	0
or	0
saline	0
injected	0
.	0

Their	0
glomeruli	0
showed	0
changes	0
of	0
progressive	0
FSGS	3
.	0

The	0
ultrastructural	0
studies	0
in	0
the	0
initial	0
stage	0
revealed	0
significant	0
lack	0
of	0
particles	0
of	0
perfused	0
ruthenium	1
red	0
on	0
the	0
lamina	0
rara	0
externa	0
and	0
marked	0
changes	0
in	0
epithelial	0
cell	0
cytoplasm	0
.	0

Therefore	0
,	0
it	0
is	0
suggested	0
that	0
the	0
administration	0
of	0
PS	1
enhances	0
the	0
toxicity	3
of	0
AMNS	1
on	0
the	0
glomerulus	0
and	0
readily	0
produces	0
progressive	0
FSGS	3
in	0
rats	0
resulting	0
in	0
the	0
end	3
-	4
stage	4
renal	4
disease	4
.	0

Theophylline	1
neurotoxicity	3
in	0
pregnant	0
rats	0
.	0

The	0
purpose	0
of	0
this	0
investigation	0
was	0
to	0
determine	0
whether	0
the	0
neurotoxicity	3
of	0
theophylline	1
is	0
altered	0
in	0
advanced	0
pregnancy	0
.	0

Sprague	0
-	0
Dawley	0
rats	0
that	0
were	0
20	0
days	0
pregnant	0
and	0
nonpregnant	0
rats	0
of	0
the	0
same	0
age	0
and	0
strain	0
received	0
infusions	0
of	0
aminophylline	1
until	0
onset	0
of	0
maximal	0
seizures	3
which	0
occurred	0
after	0
28	0
and	0
30	0
minutes	0
respectively	0
.	0

Theophylline	1
concentrations	0
at	0
this	0
endpoint	0
in	0
serum	0
(	0
total	0
)	0
and	0
CSF	0
were	0
similar	0
but	0
serum	0
(	0
free	0
)	0
and	0
brain	0
concentrations	0
were	0
slightly	0
different	0
in	0
pregnant	0
rats	0
.	0

Theophylline	1
serum	0
protein	0
binding	0
determined	0
by	0
equilibrium	0
dialysis	0
was	0
lower	0
in	0
pregnant	0
rats	0
.	0

Fetal	0
serum	0
concentrations	0
at	0
onset	0
of	0
seizures	3
in	0
the	0
mother	0
were	0
similar	0
to	0
maternal	0
brain	0
and	0
CSF	0
concentrations	0
and	0
correlated	0
significantly	0
with	0
the	0
former	0
.	0

It	0
is	0
concluded	0
that	0
advanced	0
pregnancy	0
has	0
a	0
negligible	0
effect	0
on	0
the	0
neurotoxic	3
response	0
to	0
theophylline	1
in	0
rats	0
.	0

Hyperkalemia	3
induced	0
by	0
indomethacin	1
and	0
naproxen	1
and	0
reversed	0
by	0
fludrocortisone	1
.	0

We	0
have	0
described	0
a	0
patient	0
with	0
severe	0
rheumatoid	3
arthritis	4
and	0
a	0
history	0
of	0
mefenamic	1
acid	2
nephropathy	3
in	0
whom	0
hyperkalemia	3
and	0
inappropriate	0
hypoaldosteronism	3
were	0
caused	0
by	0
both	0
indomethacin	1
and	0
naproxen	1
,	0
without	0
major	0
decline	0
in	0
renal	0
function	0
.	0

It	0
is	0
likely	0
that	0
preexisting	0
renal	3
disease	4
predisposed	0
this	0
patient	0
to	0
type	3
IV	4
renal	4
tubular	4
acidosis	4
with	0
prostaglandin	1
synthetase	0
inhibitors	0
.	0

Because	0
he	0
was	0
unable	0
to	0
discontinue	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
drug	0
therapy	0
,	0
fludrocortisone	1
was	0
added	0
,	0
correcting	0
the	0
hyperkalemia	3
and	0
allowing	0
indomethacin	1
therapy	0
to	0
be	0
continued	0
safely	0
.	0

Hypotension	3
as	0
a	0
manifestation	0
of	0
cardiotoxicity	3
in	0
three	0
patients	0
receiving	0
cisplatin	1
and	0
5	1
-	2
fluorouracil	2
.	0

Cardiac	0
symptoms	0
,	0
including	0
hypotension	3
,	0
developed	0
in	0
three	0
patients	0
with	0
advanced	0
colorectal	3
carcinoma	4
while	0
being	0
treated	0
with	0
cisplatin	1
(	0
CDDP	1
)	0
and	0
5	1
-	2
fluorouracil	2
(	0
5	1
-	2
FU	2
)	0
.	0

In	0
two	0
patients	0
,	0
hypotension	3
was	0
associated	0
with	0
severe	0
left	3
ventricular	4
dysfunction	4
.	0

All	0
three	0
patients	0
required	0
therapy	0
discontinuation	0
.	0

Cardiac	0
enzymes	0
remained	0
normal	0
despite	0
transient	0
electrocardiographic	0
(	0
EKG	0
)	0
changes	0
.	0

The	0
presentation	0
and	0
cardiac	0
evaluation	0
(	0
hemodynamic	0
,	0
echocardiographic	0
,	0
and	0
scintigraphic	0
)	0
of	0
these	0
patients	0
suggest	0
new	0
manifestations	0
of	0
5	1
-	2
FU	2
cardiotoxicity	3
that	0
may	0
be	0
influenced	0
by	0
CDDP	1
.	0

The	0
possible	0
pathophysiologic	0
mechanisms	0
are	0
discussed	0
.	0

Fatal	0
aplastic	3
anemia	4
in	0
a	0
patient	0
treated	0
with	0
carbamazepine	1
.	0

A	0
case	0
of	0
fatal	0
aplastic	3
anemia	4
due	0
to	0
carbamazepine	1
treatment	0
in	0
an	0
epileptic	3
woman	0
is	0
reported	0
.	0

Despite	0
concerns	0
of	0
fatal	0
bone	3
marrow	4
toxicity	4
due	0
to	0
carbamazepine	1
,	0
this	0
is	0
only	0
the	0
fourth	0
documented	0
and	0
published	0
report	0
.	0

Carbamazepine	1
is	0
a	0
safe	0
drug	0
,	0
but	0
physicians	0
and	0
patients	0
should	0
be	0
aware	0
of	0
the	0
exceedingly	0
rare	0
but	0
potentially	0
fatal	0
side	0
effects	0
,	0
better	0
prevented	0
by	0
clinical	0
than	0
by	0
laboratory	0
monitoring	0
.	0

Participation	0
of	0
a	0
bulbospinal	0
serotonergic	0
pathway	0
in	0
the	0
rat	0
brain	0
in	0
clonidine	1
-	0
induced	0
hypotension	3
and	0
bradycardia	3
.	0

The	0
effects	0
of	0
microinjection	0
of	0
clonidine	1
(	0
1	0
-	0
10	0
micrograms	0
in	0
1	0
microliter	0
)	0
into	0
a	0
region	0
adjacent	0
to	0
the	0
ventrolateral	0
surface	0
of	0
the	0
medulla	0
oblongata	0
on	0
cardiovascular	0
function	0
were	0
assessed	0
in	0
urethane	1
-	0
anesthetized	0
rats	0
.	0

Intramedullary	0
administration	0
of	0
clonidine	1
,	0
but	0
not	0
saline	0
vehicle	0
,	0
caused	0
a	0
dose	0
-	0
dependent	0
decrease	0
in	0
both	0
the	0
mean	0
arterial	0
pressure	0
and	0
the	0
heart	0
rate	0
.	0

The	0
clonidine	1
-	0
induced	0
hypotension	3
was	0
antagonized	0
by	0
prior	0
spinal	0
transection	0
,	0
but	0
not	0
bilateral	0
vagotomy	0
.	0

0n	0
the	0
other	0
hand	0
,	0
the	0
clonidine	1
-	0
induced	0
bradycardia	3
was	0
antagonized	0
by	0
prior	0
bilateral	0
vagotomy	0
,	0
but	0
not	0
spinal	0
transection	0
.	0

Furthermore	0
,	0
selective	0
destruction	0
of	0
the	0
spinal	0
5	1
-	2
HT	2
nerves	0
,	0
produced	0
by	0
bilateral	0
spinal	0
injection	0
of	0
5	1
,	2
7	2
-	2
dihydroxytryptamine	2
,	0
reduced	0
the	0
magnitude	0
of	0
the	0
vasodepressor	0
or	0
the	0
bradycardiac	3
responses	0
to	0
clonidine	1
microinjected	0
into	0
the	0
area	0
near	0
the	0
ventrolateral	0
surface	0
of	0
the	0
medulla	0
oblongata	0
in	0
rats	0
.	0

The	0
data	0
indicate	0
that	0
a	0
bulbospinal	0
serotonergic	0
pathway	0
is	0
involved	0
in	0
development	0
of	0
clonidine	1
-	0
induced	0
hypotension	3
and	0
bradycardia	3
.	0

The	0
induced	0
hypotension	3
is	0
brought	0
about	0
by	0
a	0
decrease	0
in	0
sympathetic	0
efferent	0
activity	0
,	0
whereas	0
the	0
induced	0
bradycardia	3
was	0
due	0
to	0
an	0
increase	0
in	0
vagal	0
efferent	0
activity	0
.	0

Hypertension	3
in	0
neuroblastoma	3
induced	0
by	0
imipramine	1
.	0

Hypertension	3
is	0
a	0
well	0
-	0
known	0
finding	0
in	0
some	0
patients	0
with	0
neuroblastoma	3
.	0

However	0
,	0
it	0
has	0
not	0
previously	0
been	0
described	0
in	0
association	0
with	0
the	0
use	0
of	0
Imipramine	1
.	0

We	0
report	0
the	0
occurrence	0
of	0
severe	0
hypertension	3
(	0
blood	0
pressure	0
190	0
/	0
160	0
)	0
in	0
a	0
4	0
-	0
year	0
-	0
old	0
girl	0
with	0
neuroblastoma	3
who	0
was	0
given	0
Imipramine	1
to	0
control	0
a	0
behavior	3
disorder	4
.	0

It	0
was	0
determined	0
later	0
that	0
this	0
patient	0
'	0
s	0
tumor	3
was	0
recurring	0
at	0
the	0
time	0
of	0
her	0
hypertensive	3
episode	0
.	0

Since	0
she	0
had	0
no	0
blood	0
pressure	0
elevation	0
at	0
initial	0
diagnosis	0
and	0
none	0
following	0
discontinuation	0
of	0
the	0
Imipramine	1
(	0
when	0
she	0
was	0
in	0
florid	0
relapse	0
)	0
,	0
we	0
believe	0
that	0
this	0
drug	0
rather	0
than	0
her	0
underlying	0
disease	0
alone	0
caused	0
her	0
hypertension	3
.	0

The	0
mechanism	0
for	0
this	0
reaction	0
is	0
believed	0
to	0
be	0
increased	0
levels	0
of	0
vasoactive	0
catecholamines	1
due	0
to	0
interference	0
of	0
their	0
physiologic	0
inactivation	0
by	0
Imipramine	1
.	0

From	0
this	0
experience	0
,	0
we	0
urge	0
extreme	0
caution	0
in	0
the	0
use	0
of	0
tricyclic	0
antidepressants	0
in	0
children	0
with	0
active	0
neuroblastoma	3
.	0

Rechallenge	0
of	0
patients	0
who	0
developed	0
oral	3
candidiasis	4
or	0
hoarseness	3
with	0
beclomethasone	1
dipropionate	2
.	0

0f	0
158	0
asthmatic	3
patients	0
who	0
were	0
placed	0
on	0
inhaled	0
beclomethasone	1
,	0
15	0
(	0
9	0
.	0
5	0
%	0
)	0
developed	0
either	0
hoarseness	3
(	0
8	0
)	0
,	0
oral	0
thrush	3
(	0
6	0
)	0
,	0
or	0
both	0
(	0
1	0
)	0
.	0

When	0
their	0
adverse	0
reactions	0
subsided	0
,	0
seven	0
of	0
these	0
15	0
patients	0
were	0
rechallenged	0
with	0
inhaled	0
beclomethasone	1
.	0

These	0
included	0
five	0
cases	0
who	0
developed	0
hoarseness	3
and	0
three	0
who	0
developed	0
Candidiasis	3
.	0

0ne	0
patient	0
had	0
both	0
.	0

0ral	0
thrush	3
did	0
not	0
recur	0
,	0
but	0
60	0
%	0
(	0
3	0
/	0
5	0
)	0
of	0
patients	0
with	0
hoarseness	3
had	0
recurrence	0
.	0

We	0
conclude	0
that	0
patients	0
may	0
be	0
restarted	0
on	0
inhaled	0
beclomethasone	1
when	0
clinically	0
indicated	0
;	0
however	0
,	0
because	0
of	0
the	0
high	0
recurrence	0
rate	0
,	0
patients	0
who	0
develop	0
hoarseness	3
should	0
not	0
be	0
re	0
-	0
challenged	0
.	0

Concomitant	0
use	0
of	0
oral	0
prednisone	1
and	0
topical	0
beclomethasone	1
may	0
increase	0
the	0
risk	0
of	0
developing	0
hoarseness	3
or	0
candidiasis	3
.	0

Cyclophosphamide	1
cardiotoxicity	3
:	0
an	0
analysis	0
of	0
dosing	0
as	0
a	0
risk	0
factor	0
.	0

Patients	0
who	0
undergo	0
bone	0
marrow	0
transplantation	0
are	0
generally	0
immunosuppressed	0
with	0
a	0
dose	0
of	0
cyclophosphamide	1
(	0
CYA	1
)	0
which	0
is	0
usually	0
calculated	0
based	0
on	0
the	0
patient	0
'	0
s	0
weight	0
.	0

At	0
these	0
high	0
doses	0
of	0
CYA	1
,	0
serious	0
cardiotoxicity	3
may	0
occur	0
,	0
but	0
definitive	0
risk	0
factors	0
for	0
the	0
development	0
of	0
such	0
cardiotoxicity	3
have	0
not	0
been	0
described	0
.	0

Since	0
chemotherapeutic	0
agent	0
toxicity	3
generally	0
correlates	0
with	0
dose	0
per	0
body	0
surface	0
area	0
,	0
we	0
retrospectively	0
calculated	0
the	0
dose	0
of	0
CYA	1
in	0
patients	0
transplanted	0
at	0
our	0
institution	0
to	0
determine	0
whether	0
the	0
incidence	0
of	0
CYA	1
cardiotoxicity	3
correlated	0
with	0
the	0
dose	0
per	0
body	0
surface	0
area	0
.	0

Eighty	0
patients	0
who	0
were	0
to	0
receive	0
CYA	1
50	0
mg	0
/	0
kg	0
/	0
d	0
for	0
four	0
days	0
as	0
preparation	0
for	0
marrow	0
grafting	0
underwent	0
a	0
total	0
of	0
84	0
transplants	0
for	0
aplastic	3
anemia	4
,	0
Wiskott	3
-	4
Aldrich	4
syndrome	4
,	0
or	0
severe	3
combined	4
immunodeficiency	4
syndrome	4
.	0

Fourteen	0
of	0
84	0
(	0
17	0
%	0
)	0
patients	0
had	0
symptoms	0
and	0
signs	0
consistent	0
with	0
CYA	1
cardiotoxicity	3
within	0
ten	0
days	0
of	0
receiving	0
1	0
to	0
4	0
doses	0
of	0
CYA	1
.	0

Six	0
of	0
the	0
14	0
patients	0
died	0
with	0
congestive	3
heart	4
failure	4
.	0

The	0
dose	0
of	0
CYA	1
per	0
body	0
surface	0
area	0
was	0
calculated	0
for	0
all	0
patients	0
and	0
the	0
patients	0
were	0
divided	0
into	0
two	0
groups	0
based	0
on	0
daily	0
CYA	1
dose	0
:	0
Group	0
1	0
,	0
CYA	1
less	0
than	0
or	0
equal	0
to	0
1	0
.	0
55	0
g	0
/	0
m2	0
/	0
d	0
;	0
Group	0
2	0
,	0
CYA	1
greater	0
than	0
1	0
.	0
55	0
g	0
/	0
m2	0
/	0
d	0
.	0

Cardiotoxicity	3
that	0
was	0
thought	0
to	0
be	0
related	0
to	0
CYA	1
occurred	0
in	0
1	0
/	0
32	0
(	0
3	0
%	0
)	0
of	0
patients	0
in	0
Group	0
1	0
and	0
in	0
13	0
/	0
52	0
(	0
25	0
%	0
)	0
patients	0
in	0
Group	0
2	0
(	0
P	0
less	0
than	0
0	0
.	0
025	0
)	0
.	0

Congestive	3
heart	4
failure	4
caused	0
or	0
contributed	0
to	0
death	0
in	0
0	0
/	0
32	0
patients	0
in	0
Group	0
1	0
v	0
6	0
/	0
52	0
(	0
12	0
%	0
)	0
of	0
patients	0
in	0
Group	0
2	0
(	0
P	0
less	0
than	0
0	0
.	0
25	0
)	0
.	0

There	0
was	0
no	0
difference	0
in	0
the	0
rate	0
of	0
engraftment	0
of	0
evaluable	0
patients	0
in	0
the	0
two	0
groups	0
(	0
P	0
greater	0
than	0
0	0
.	0
5	0
)	0
.	0

We	0
conclude	0
that	0
the	0
CYA	1
cardiotoxicity	3
correlates	0
with	0
CYA	1
dosage	0
as	0
calculated	0
by	0
body	0
surface	0
area	0
,	0
and	0
that	0
patients	0
with	0
aplastic	3
anemia	4
and	0
immunodeficiencies	3
can	0
be	0
effectively	0
prepared	0
for	0
bone	0
marrow	0
grafting	0
at	0
a	0
CYA	1
dose	0
of	0
1	0
.	0
55	0
g	0
/	0
m2	0
/	0
d	0
for	0
four	0
days	0
with	0
a	0
lower	0
incidence	0
of	0
cardiotoxicity	3
than	0
patients	0
whose	0
CYA	1
dosage	0
is	0
calculated	0
based	0
on	0
weight	0
.	0

This	0
study	0
reaffirms	0
the	0
principle	0
that	0
drug	0
toxicity	3
correlates	0
with	0
dose	0
per	0
body	0
surface	0
area	0
.	0

Studies	0
of	0
risk	0
factors	0
for	0
aminoglycoside	1
nephrotoxicity	3
.	0

The	0
epidemiology	0
of	0
aminoglycoside	1
-	0
induced	0
nephrotoxicity	3
is	0
not	0
fully	0
understood	0
.	0

Experimental	0
studies	0
in	0
healthy	0
human	0
volunteers	0
indicate	0
aminoglycosides	1
cause	0
proximal	0
tubular	0
damage	0
in	0
most	0
patients	0
,	0
but	0
rarely	0
,	0
if	0
ever	0
,	0
cause	0
glomerular	3
or	4
tubular	4
dysfunction	4
.	0

Clinical	0
trials	0
of	0
aminoglycosides	1
in	0
seriously	0
ill	0
patients	0
indicate	0
that	0
the	0
relative	0
risk	0
for	0
developing	0
acute	3
renal	4
failure	4
during	0
therapy	0
ranges	0
from	0
8	0
to	0
10	0
and	0
that	0
the	0
attributable	0
risk	0
is	0
70	0
%	0
to	0
80	0
%	0
.	0

Further	0
analysis	0
of	0
these	0
data	0
suggests	0
that	0
the	0
duration	0
of	0
therapy	0
,	0
plasma	0
aminoglycoside	1
levels	0
,	0
liver	3
disease	4
,	0
advanced	0
age	0
,	0
high	0
initial	0
estimated	0
creatinine	1
clearance	0
and	0
,	0
possibly	0
,	0
female	0
gender	0
all	0
increase	0
the	0
risk	0
for	0
nephrotoxicity	3
.	0

0ther	0
causes	0
of	0
acute	3
renal	4
failure	4
,	0
such	0
as	0
shock	3
,	0
appear	0
to	0
have	0
an	0
additive	0
effect	0
.	0

Predictive	0
models	0
have	0
been	0
developed	0
from	0
these	0
analyses	0
that	0
should	0
be	0
useful	0
for	0
identifying	0
patients	0
at	0
high	0
risk	0
.	0

These	0
models	0
may	0
also	0
be	0
useful	0
in	0
developing	0
insights	0
into	0
the	0
pathophysiology	0
of	0
aminoglycoside	1
-	0
induced	0
nephrotoxicity	3
.	0

Central	0
action	0
of	0
narcotic	0
analgesics	0
.	0

Part	0
IV	0
.	0

Noradrenergic	0
influences	0
on	0
the	0
activity	0
of	0
analgesics	0
in	0
rats	0
.	0

The	0
effect	0
of	0
clonidine	1
,	0
naphazoline	1
and	0
xylometazoline	1
on	0
analgesia	0
induced	0
by	0
morphine	1
,	0
codeine	1
,	0
fentanyl	1
and	0
pentazocine	1
,	0
and	0
on	0
cataleptic	3
effect	0
of	0
morphine	1
,	0
codine	1
and	0
fentanyl	1
was	0
studied	0
in	0
rats	0
.	0

The	0
biochemical	0
assays	0
on	0
the	0
influence	0
of	0
four	0
analgesics	0
on	0
the	0
brain	0
concentration	0
and	0
turnover	0
of	0
noradrenaline	1
(	0
NA	1
)	0
were	0
also	0
performed	0
.	0

It	0
was	0
found	0
that	0
three	0
drugs	0
stimulating	0
central	0
NA	1
receptors	0
failed	0
to	0
affect	0
the	0
analgesic	0
ED50	0
of	0
all	0
antinociceptive	0
agents	0
and	0
they	0
enhanced	0
catalepsy	3
induced	0
by	0
morphine	1
and	0
fentanyl	1
.	0

Codeine	1
catalepsy	3
was	0
increased	0
by	0
clonidine	1
and	0
decreased	0
by	0
naphazoline	1
and	0
xylometazoline	1
.	0

The	0
brain	0
concentration	0
of	0
NA	1
was	0
not	0
changed	0
by	0
morphine	1
and	0
fentanyl	1
,	0
but	0
one	0
of	0
the	0
doses	0
of	0
codeine	1
(	0
45	0
mg	0
/	0
kg	0
)	0
slightly	0
enhanced	0
it	0
.	0

Pentazocine	1
dose	0
-	0
dependently	0
decreased	0
the	0
brain	0
level	0
of	0
NA	1
.	0

The	0
rate	0
of	0
NA	1
turnover	0
was	0
not	0
altered	0
by	0
analgesics	0
except	0
for	0
the	0
higher	0
dose	0
of	0
fentanyl	1
(	0
0	0
.	0
2	0
mg	0
/	0
kg	0
)	0
following	0
which	0
the	0
disappearance	0
of	0
NA	1
from	0
the	0
brain	0
was	0
diminished	0
.	0

The	0
results	0
are	0
discussed	0
in	0
the	0
light	0
of	0
various	0
and	0
non	0
-	0
uniform	0
data	0
from	0
the	0
literature	0
.	0

It	0
is	0
suggested	0
that	0
in	0
rats	0
the	0
brain	0
NA	1
plays	0
a	0
less	0
important	0
function	0
than	0
the	0
other	0
monoamines	1
in	0
the	0
behavioural	0
activity	0
of	0
potent	0
analgesics	0
.	0

Flurothyl	1
seizure	3
thresholds	0
in	0
mice	0
treated	0
neonatally	0
with	0
a	0
single	0
injection	0
of	0
monosodium	1
glutamate	2
(	0
MSG	1
)	0
:	0
evaluation	0
of	0
experimental	0
parameters	0
in	0
flurothyl	1
seizure	3
testing	0
.	0

Monosodium	1
glutamate	2
(	0
MSG	1
)	0
administration	0
to	0
neonatal	0
rodents	0
produces	0
convulsions	3
and	0
results	0
in	0
numerous	0
biochemical	0
and	0
behavioral	0
deficits	0
.	0

These	0
studies	0
were	0
undertaken	0
to	0
determine	0
if	0
neonatal	0
administration	0
of	0
MSG	1
produced	0
permanent	0
alterations	0
in	0
seizure	3
susceptibility	0
,	0
since	0
previous	0
investigations	0
were	0
inconclusive	0
.	0

A	0
flurothyl	1
ether	1
seizure	3
screening	0
technique	0
was	0
used	0
to	0
evaluate	0
seizure	3
susceptibility	0
in	0
adult	0
mice	0
that	0
received	0
neonatal	0
injections	0
of	0
MSG	1
(	0
4	0
mg	0
/	0
g	0
and	0
1	0
mg	0
/	0
g	0
)	0
.	0

MSG	1
treatment	0
resulted	0
in	0
significant	0
reductions	0
in	0
whole	0
brain	0
weight	0
but	0
did	0
not	0
alter	0
seizure	3
threshold	0
.	0

A	0
naloxone	1
(	0
5	0
mg	0
/	0
kg	0
)	0
challenge	0
was	0
also	0
ineffective	0
in	0
altering	0
the	0
seizure	3
thresholds	0
of	0
either	0
control	0
of	0
MSG	1
-	0
treated	0
mice	0
.	0

Flurothyl	1
ether	1
produced	0
hypothermia	3
which	0
was	0
correlated	0
with	0
the	0
duration	0
of	0
flurothyl	1
exposure	0
;	0
however	0
,	0
the	0
relationship	0
of	0
hypothermia	3
to	0
seizure	3
induction	0
was	0
unclear	0
.	0

Flurothyl	1
seizure	3
testing	0
proved	0
to	0
be	0
a	0
rapid	0
and	0
reliable	0
technique	0
with	0
which	0
to	0
evaluate	0
seizure	3
susceptibility	0
.	0

Susceptibility	0
to	0
seizures	3
produced	0
by	0
pilocarpine	1
in	0
rats	0
after	0
microinjection	0
of	0
isoniazid	1
or	0
gamma	1
-	2
vinyl	2
-	2
GABA	2
into	0
the	0
substantia	0
nigra	0
.	0

Pilocarpine	1
,	0
given	0
intraperitoneally	0
to	0
rats	0
,	0
reproduces	0
the	0
neuropathological	0
sequelae	0
of	0
temporal	3
lobe	4
epilepsy	4
and	0
provides	0
a	0
relevant	0
animal	0
model	0
for	0
studying	0
mechanisms	0
of	0
buildup	0
of	0
convulsive	3
activity	0
and	0
pathways	0
operative	0
in	0
the	0
generalization	0
and	0
propagation	0
of	0
seizures	3
within	0
the	0
forebrain	0
.	0

In	0
the	0
present	0
study	0
,	0
the	0
effects	0
of	0
manipulating	0
the	0
activity	0
of	0
the	0
gamma	1
-	2
aminobutyric	2
acid	2
(	0
GABA	1
)	0
-	0
mediated	0
synaptic	0
inhibition	0
within	0
the	0
substantia	0
nigra	0
on	0
seizures	3
produced	0
by	0
pilocarpine	1
in	0
rats	0
,	0
were	0
investigated	0
.	0

In	0
animals	0
pretreated	0
with	0
microinjections	0
of	0
isoniazid	1
,	0
150	0
micrograms	0
,	0
an	0
inhibitor	0
of	0
activity	0
of	0
the	0
GABA	1
-	0
synthesizing	0
enzyme	0
,	0
L	1
-	2
glutamic	2
acid	2
decarboxylase	0
,	0
into	0
the	0
substantia	0
nigra	0
pars	0
reticulata	0
(	0
SNR	0
)	0
,	0
bilaterally	0
,	0
non	0
-	0
convulsant	0
doses	0
of	0
pilocarpine	1
,	0
100	0
and	0
200	0
mg	0
/	0
kg	0
,	0
resulted	0
in	0
severe	0
motor	0
limbic	0
seizures	3
and	0
status	3
epilepticus	4
.	0

Electroencephalographic	0
and	0
behavioral	0
monitoring	0
revealed	0
a	0
profound	0
reduction	0
of	0
the	0
threshold	0
for	0
pilocarpine	1
-	0
induced	0
convulsions	3
.	0

Morphological	0
analysis	0
of	0
frontal	0
forebrain	0
sections	0
with	0
light	0
microscopy	0
revealed	0
seizure	3
-	0
related	0
damage	0
to	0
the	0
hippocampal	0
formation	0
,	0
thalamus	0
,	0
amygdala	0
,	0
olfactory	0
cortex	0
,	0
substantia	0
nigra	0
and	0
neocortex	0
,	0
which	0
is	0
typically	0
observed	0
with	0
pilocarpine	1
in	0
doses	0
exceeding	0
350	0
mg	0
/	0
kg	0
.	0

Bilateral	0
intrastriatal	0
injections	0
of	0
isoniazid	1
did	0
not	0
augment	0
seizures	3
produced	0
by	0
pilocarpine	1
,	0
200	0
mg	0
/	0
kg	0
.	0

Application	0
of	0
an	0
irreversible	0
inhibitor	0
of	0
GABA	1
transaminase	0
,	0
gamma	1
-	2
vinyl	2
-	2
GABA	2
(	0
D	1
,	2
L	2
-	2
4	2
-	2
amino	2
-	2
hex	2
-	2
5	2
-	2
enoic	2
acid	2
)	0
,	0
5	0
micrograms	0
,	0
into	0
the	0
SNR	0
,	0
bilaterally	0
,	0
suppressed	0
the	0
appearance	0
of	0
electrographic	0
and	0
behavioral	0
seizures	3
produced	0
by	0
pilocarpine	1
,	0
380	0
mg	0
/	0
kg	0
.	0

This	0
treatment	0
was	0
also	0
sufficient	0
to	0
protect	0
animals	0
from	0
the	0
occurrence	0
of	0
brain	3
damage	4
.	0

Microinjections	0
of	0
gamma	1
-	2
vinyl	2
-	2
GABA	2
,	0
5	0
micrograms	0
,	0
into	0
the	0
dorsal	0
striatum	0
,	0
bilaterally	0
,	0
failed	0
to	0
prevent	0
the	0
development	0
of	0
convulsions	3
produced	0
by	0
pilocarpine	1
,	0
380	0
mg	0
/	0
kg	0
.	0

The	0
results	0
demonstrate	0
that	0
the	0
threshold	0
for	0
pilocarpine	1
-	0
induced	0
seizures	3
in	0
rats	0
is	0
subjected	0
to	0
the	0
regulation	0
of	0
the	0
GABA	1
-	0
mediated	0
synaptic	0
inhibition	0
within	0
the	0
substantia	0
nigra	0
.	0

Human	0
and	0
canine	0
ventricular	0
vasoactive	0
intestinal	0
polypeptide	0
:	0
decrease	0
with	0
heart	3
failure	4
.	0

Vasoactive	0
intestinal	0
polypeptide	0
(	0
VIP	0
)	0
is	0
a	0
systemic	0
and	0
coronary	0
vasodilator	0
that	0
may	0
have	0
positive	0
inotropic	0
properties	0
.	0

Myocardial	0
levels	0
of	0
VIP	0
were	0
assayed	0
before	0
and	0
after	0
the	0
development	0
of	0
heart	3
failure	4
in	0
two	0
canine	0
models	0
.	0

In	0
the	0
first	0
,	0
cobalt	1
cardiomyopathy	3
was	0
induced	0
in	0
eight	0
dogs	0
;	0
VIP	0
(	0
by	0
radioimmunoassay	0
)	0
decreased	0
from	0
35	0
+	0
/	0
-	0
11	0
pg	0
/	0
mg	0
protein	0
(	0
mean	0
+	0
/	0
-	0
SD	0
)	0
to	0
5	0
+	0
/	0
-	0
4	0
pg	0
/	0
mg	0
protein	0
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

In	0
six	0
dogs	0
with	0
doxorubicin	1
-	0
induced	0
heart	3
failure	4
,	0
VIP	0
decreased	0
from	0
31	0
+	0
/	0
-	0
7	0
to	0
11	0
+	0
/	0
-	0
4	0
pg	0
/	0
mg	0
protein	0
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

In	0
addition	0
,	0
VIP	0
content	0
of	0
left	0
ventricular	0
muscle	0
of	0
resected	0
failing	0
hearts	0
in	0
10	0
patients	0
receiving	0
a	0
heart	0
transplant	0
was	0
compared	0
with	0
the	0
papillary	0
muscles	0
in	0
14	0
patients	0
(	0
five	0
with	0
rheumatic	3
disease	4
,	0
nine	0
with	0
myxomatous	3
degeneration	4
)	0
receiving	0
mitral	0
valve	0
prostheses	0
.	0

The	0
lowest	0
myocardial	0
VIP	0
concentration	0
was	0
found	0
in	0
the	0
hearts	0
of	0
patients	0
with	0
coronary	3
disease	4
(	0
one	0
patient	0
receiving	0
a	0
transplant	0
and	0
three	0
receiving	0
mitral	0
prostheses	0
)	0
(	0
6	0
.	0
3	0
+	0
/	0
-	0
1	0
.	0
9	0
pg	0
/	0
mg	0
protein	0
)	0
.	0

The	0
other	0
patients	0
undergoing	0
transplantation	0
had	0
an	0
average	0
ejection	0
fraction	0
of	0
17	0
%	0
+	0
/	0
-	0
6	0
%	0
and	0
a	0
VIP	0
level	0
of	0
8	0
.	0
8	0
+	0
/	0
-	0
3	0
.	0
9	0
pg	0
/	0
mg	0
protein	0
.	0

The	0
hearts	0
without	0
coronary	3
artery	4
disease	4
(	0
average	0
ejection	0
fraction	0
of	0
this	0
group	0
62	0
%	0
+	0
/	0
-	0
10	0
%	0
)	0
had	0
a	0
VIP	0
concentration	0
of	0
14	0
.	0
1	0
+	0
/	0
-	0
7	0
.	0
9	0
pg	0
/	0
mg	0
protein	0
,	0
and	0
this	0
was	0
greater	0
than	0
in	0
hearts	0
of	0
the	0
patients	0
with	0
coronary	3
disease	4
and	0
the	0
hearts	0
of	0
patients	0
receiving	0
a	0
transplant	0
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

Myocardial	0
catecholamines	1
were	0
also	0
determined	0
in	0
14	0
subjects	0
;	0
a	0
weak	0
correlation	0
(	0
r	0
=	0
0	0
.	0
57	0
,	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
between	0
the	0
tissue	0
concentrations	0
of	0
VIP	0
and	0
norepinephrine	1
was	0
noted	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Non	0
-	0
invasive	0
detection	0
of	0
coronary	3
artery	4
disease	4
by	0
body	0
surface	0
electrocardiographic	0
mapping	0
after	0
dipyridamole	1
infusion	0
.	0

Electrocardiographic	0
changes	0
after	0
dipyridamole	1
infusion	0
(	0
0	0
.	0
568	0
mg	0
/	0
kg	0
/	0
4	0
min	0
)	0
were	0
studied	0
in	0
41	0
patients	0
with	0
coronary	3
artery	4
disease	4
and	0
compared	0
with	0
those	0
after	0
submaximal	0
treadmill	0
exercise	0
by	0
use	0
of	0
the	0
body	0
surface	0
mapping	0
technique	0
.	0

Patients	0
were	0
divided	0
into	0
three	0
groups	0
;	0
19	0
patients	0
without	0
myocardial	3
infarction	4
(	0
non	0
-	0
MI	3
group	0
)	0
,	0
14	0
with	0
anterior	3
infarction	4
(	0
ANT	3
-	4
MI	4
)	0
and	0
eight	0
with	0
inferior	3
infarction	4
(	0
INF	3
-	4
MI	4
)	0
.	0

Eighty	0
-	0
seven	0
unipolar	0
electrocardiograms	0
(	0
ECGs	0
)	0
distributed	0
over	0
the	0
entire	0
thoracic	0
surface	0
were	0
simultaneously	0
recorded	0
.	0

After	0
dipyridamole	1
,	0
ischemic	3
ST	0
-	0
segment	0
depression	3
(	0
0	0
.	0
05	0
mV	0
or	0
more	0
)	0
was	0
observed	0
in	0
84	0
%	0
of	0
the	0
non	0
-	0
MI	3
group	0
,	0
29	0
%	0
of	0
the	0
ANT	3
-	4
MI	4
group	0
,	0
63	0
%	0
of	0
the	0
INF	3
-	4
MI	4
group	0
and	0
61	0
%	0
of	0
the	0
total	0
population	0
.	0

Exercise	0
-	0
induced	0
ST	0
depression	3
was	0
observed	0
in	0
84	0
%	0
of	0
the	0
non	0
-	0
MI	3
group	0
,	0
43	0
%	0
of	0
the	0
ANT	3
-	4
MI	4
group	0
,	0
38	0
%	0
of	0
the	0
INF	3
-	4
MI	4
group	0
and	0
61	0
%	0
of	0
the	0
total	0
.	0

For	0
individual	0
patients	0
,	0
there	0
were	0
no	0
obvious	0
differences	0
between	0
the	0
body	0
surface	0
distribution	0
of	0
ST	0
depression	3
in	0
both	0
tests	0
.	0

The	0
increase	0
in	0
pressure	0
rate	0
product	0
after	0
dipyridamole	1
was	0
significantly	0
less	0
than	0
that	0
during	0
the	0
treadmill	0
exercise	0
.	0

The	0
data	0
suggest	0
that	0
the	0
dipyridamole	1
-	0
induced	0
myocardial	3
ischemia	4
is	0
caused	0
by	0
the	0
inhomogenous	0
distribution	0
of	0
myocardial	0
blood	0
flow	0
.	0

We	0
conclude	0
that	0
the	0
dipyridamole	1
ECG	0
test	0
is	0
as	0
useful	0
as	0
the	0
exercise	0
ECG	0
test	0
for	0
the	0
assessment	0
of	0
coronary	3
artery	4
disease	4
.	0

Bradycardia	3
after	0
high	0
-	0
dose	0
intravenous	0
methylprednisolone	1
therapy	0
.	0

In	0
5	0
consecutive	0
patients	0
with	0
rheumatoid	3
arthritis	4
who	0
received	0
intravenous	0
high	0
-	0
dose	0
methylprednisolone	1
(	0
MP	1
)	0
therapy	0
(	0
1	0
g	0
daily	0
for	0
2	0
or	0
3	0
consecutive	0
days	0
)	0
,	0
a	0
decline	0
in	0
pulse	0
rate	0
was	0
observed	0
,	0
most	0
pronounced	0
on	0
day	0
4	0
.	0

In	0
one	0
of	0
the	0
5	0
patients	0
the	0
bradycardia	3
was	0
associated	0
with	0
complaints	0
of	0
substernal	0
pressure	0
.	0

Reversal	0
to	0
normal	0
heart	0
rate	0
was	0
found	0
on	0
day	0
7	0
.	0

Electrocardiographic	0
registrations	0
showed	0
sinus	3
bradycardia	4
in	0
all	0
cases	0
.	0

No	0
significant	0
changes	0
in	0
plasma	0
concentrations	0
of	0
electrolytes	0
were	0
found	0
.	0

Careful	0
observation	0
of	0
patients	0
receiving	0
high	0
-	0
dose	0
MP	1
is	0
recommended	0
.	0

High	0
-	0
dose	0
MP	1
may	0
be	0
contraindicated	0
in	0
patients	0
with	0
known	0
heart	3
disease	4
.	0

Two	0
cases	0
of	0
downbeat	3
nystagmus	4
and	0
oscillopsia	3
associated	0
with	0
carbamazepine	1
.	0

Downbeat	3
nystagmus	4
is	0
often	0
associated	0
with	0
structural	0
lesions	0
at	0
the	0
craniocervical	0
junction	0
,	0
but	0
has	0
occasionally	0
been	0
reported	0
as	0
a	0
manifestation	0
of	0
metabolic	0
imbalance	0
or	0
drug	0
intoxication	0
.	0

We	0
recorded	0
the	0
eye	0
movements	0
of	0
two	0
patients	0
with	0
reversible	0
downbeat	3
nystagmus	4
related	0
to	0
carbamazepine	1
therapy	0
.	0

The	0
nystagmus	3
of	0
both	0
patients	0
resolved	0
after	0
reduction	0
of	0
the	0
serum	0
carbamazepine	1
levels	0
.	0

Neuroradiologic	0
investigations	0
including	0
magnetic	0
resonance	0
imaging	0
scans	0
in	0
both	0
patients	0
showed	0
no	0
evidence	0
of	0
intracranial	0
abnormality	0
.	0

In	0
patients	0
with	0
downbeat	3
nystagmus	4
who	0
are	0
taking	0
anticonvulsant	0
medications	0
,	0
consideration	0
should	0
be	0
given	0
to	0
reduction	0
in	0
dose	0
before	0
further	0
investigation	0
is	0
undertaken	0
.	0

Improvement	0
by	0
denopamine	1
(	0
TA	1
-	2
064	2
)	0
of	0
pentobarbital	1
-	0
induced	0
cardiac	3
failure	4
in	0
the	0
dog	0
heart	0
-	0
lung	0
preparation	0
.	0

The	0
efficacy	0
of	0
denopamine	1
,	0
an	0
orally	0
active	0
beta	0
1	0
-	0
adrenoceptor	0
agonist	0
,	0
in	0
improving	0
cardiac	3
failure	4
was	0
assessed	0
in	0
dog	0
heart	0
-	0
lung	0
preparations	0
.	0

Cardiac	0
functions	0
depressed	0
by	0
pentobarbital	1
(	0
118	0
+	0
/	0
-	0
28	0
mg	0
;	0
mean	0
value	0
+	0
/	0
-	0
SD	0
)	0
such	0
that	0
cardiac	0
output	0
and	0
maximum	0
rate	0
of	0
rise	0
of	0
left	0
ventricular	0
pressure	0
(	0
LV	0
dP	0
/	0
dt	0
max	0
)	0
had	0
been	0
reduced	0
by	0
about	0
35	0
%	0
and	0
26	0
%	0
of	0
the	0
respective	0
controls	0
were	0
improved	0
by	0
denopamine	1
(	0
10	0
-	0
300	0
micrograms	0
)	0
in	0
a	0
dose	0
-	0
dependent	0
manner	0
.	0

With	0
100	0
micrograms	0
denopamine	1
,	0
almost	0
complete	0
restoration	0
of	0
cardiac	0
performance	0
was	0
attained	0
,	0
associated	0
with	0
a	0
slight	0
increase	0
in	0
heart	0
rate	0
.	0

No	0
arrhythmias	3
were	0
induced	0
by	0
these	0
doses	0
of	0
denopamine	1
.	0

The	0
results	0
warrant	0
clinical	0
trials	0
of	0
denopamine	1
in	0
the	0
treatment	0
of	0
cardiac	3
failure	4
.	0

Clonazepam	1
monotherapy	0
for	0
epilepsy	3
in	0
childhood	0
.	0

Sixty	0
patients	0
(	0
age	0
-	0
range	0
one	0
month	0
to	0
14	0
years	0
)	0
with	0
other	0
types	0
of	0
epilepsy	3
than	0
infantile	3
spasms	4
were	0
treated	0
with	0
clonazepam	1
.	0

Disappearance	0
of	0
seizures	3
and	0
normalization	0
of	0
abnormal	0
EEG	0
with	0
disappearance	0
of	0
seizures	3
were	0
recognized	0
in	0
77	0
%	0
and	0
50	0
%	0
,	0
respectively	0
.	0

Seizures	3
disappeared	0
in	0
71	0
%	0
of	0
the	0
patients	0
with	0
generalized	0
seizures	3
and	0
89	0
%	0
of	0
partial	0
seizures	3
.	0

Improvement	0
of	0
abnormal	0
EEG	0
was	0
noticed	0
in	0
76	0
%	0
of	0
diffuse	0
paroxysms	0
and	0
in	0
67	0
%	0
of	0
focal	0
paroxysms	0
.	0

In	0
excellent	0
cases	0
,	0
mean	0
effective	0
dosages	0
were	0
0	0
.	0
086	0
+	0
/	0
-	0
0	0
.	0
021	0
mg	0
/	0
kg	0
/	0
day	0
in	0
infants	0
and	0
0	0
.	0
057	0
+	0
/	0
-	0
0	0
.	0
022	0
mg	0
/	0
kg	0
/	0
day	0
in	0
schoolchildren	0
,	0
this	0
difference	0
was	0
statistically	0
significant	0
(	0
p	0
less	0
than	0
0	0
.	0
005	0
)	0
.	0

The	0
incidence	0
of	0
side	0
effects	0
such	0
as	0
drowsiness	3
and	0
ataxia	3
was	0
only	0
5	0
%	0
.	0

Postmarketing	0
study	0
of	0
timolol	1
-	0
hydrochlorothiazide	1
antihypertensive	0
therapy	0
.	0

A	0
postmarketing	0
surveillance	0
study	0
was	0
conducted	0
to	0
determine	0
the	0
safety	0
and	0
efficacy	0
of	0
a	0
fixed	0
-	0
ratio	0
combination	0
containing	0
10	0
mg	0
of	0
timolol	1
maleate	2
and	0
25	0
mg	0
of	0
hydrochlorothiazide	1
,	0
administered	0
twice	0
daily	0
for	0
one	0
month	0
to	0
hypertensive	3
patients	0
.	0

Data	0
on	0
9	0
,	0
037	0
patients	0
were	0
collected	0
by	0
1	0
,	0
455	0
participating	0
physicians	0
.	0

Mean	0
systolic	0
blood	0
pressure	0
decreased	0
25	0
mmHg	0
and	0
mean	0
diastolic	0
blood	0
pressure	0
declined	0
15	0
mmHg	0
after	0
one	0
month	0
of	0
timolol	1
-	0
hydrochlorothiazide	1
therapy	0
(	0
P	0
less	0
than	0
0	0
.	0
01	0
,	0
both	0
comparisons	0
)	0
.	0

Age	0
,	0
race	0
,	0
and	0
sex	0
appeared	0
to	0
have	0
no	0
influence	0
on	0
the	0
decrease	0
in	0
blood	0
pressure	0
.	0

The	0
antihypertensive	0
effect	0
of	0
the	0
drug	0
was	0
greater	0
in	0
patients	0
with	0
more	0
severe	0
hypertension	3
.	0

0verall	0
,	0
1	0
,	0
453	0
patients	0
experienced	0
a	0
total	0
of	0
2	0
,	0
658	0
adverse	0
events	0
,	0
the	0
most	0
common	0
being	0
fatigue	3
,	0
dizziness	3
,	0
and	0
weakness	3
.	0

Treatment	0
in	0
590	0
patients	0
was	0
discontinued	0
because	0
of	0
adverse	0
events	0
.	0

Salicylate	1
nephropathy	3
in	0
the	0
Gunn	0
rat	0
:	0
potential	0
role	0
of	0
prostaglandins	1
.	0

We	0
examined	0
the	0
potential	0
role	0
of	0
prostaglandins	1
in	0
the	0
development	0
of	0
analgesic	0
nephropathy	3
in	0
the	0
Gunn	0
strain	0
of	0
rat	0
.	0

The	0
homozygous	0
Gunn	0
rats	0
have	0
unconjugated	0
hyperbilirubinemia	3
due	0
to	0
the	0
absence	0
of	0
glucuronyl	1
transferase	0
,	0
leading	0
to	0
marked	0
bilirubin	1
deposition	0
in	0
renal	0
medulla	0
and	0
papilla	0
.	0

These	0
rats	0
are	0
also	0
highly	0
susceptible	0
to	0
develop	0
papillary	3
necrosis	4
with	0
analgesic	0
administration	0
.	0

We	0
used	0
homozygous	0
(	0
jj	0
)	0
and	0
phenotypically	0
normal	0
heterozygous	0
(	0
jJ	0
)	0
animals	0
.	0

Four	0
groups	0
of	0
rats	0
(	0
n	0
=	0
7	0
)	0
were	0
studied	0
:	0
jj	0
and	0
jJ	0
rats	0
treated	0
either	0
with	0
aspirin	1
300	0
mg	0
/	0
kg	0
every	0
other	0
day	0
or	0
sham	0
-	0
treated	0
.	0

After	0
one	0
week	0
,	0
slices	0
of	0
cortex	0
,	0
outer	0
and	0
inner	0
medulla	0
from	0
one	0
kidney	0
were	0
incubated	0
in	0
buffer	0
and	0
prostaglandin	1
synthesis	0
was	0
determined	0
by	0
radioimmunoassay	0
.	0

The	0
other	0
kidney	0
was	0
examined	0
histologically	0
.	0

A	0
marked	0
corticomedullary	0
gradient	0
of	0
prostaglandin	1
synthesis	0
was	0
observed	0
in	0
all	0
groups	0
.	0

PGE2	1
synthesis	0
was	0
significantly	0
higher	0
in	0
outer	0
medulla	0
,	0
but	0
not	0
cortex	0
or	0
inner	0
medulla	0
,	0
of	0
jj	0
(	0
38	0
+	0
/	0
-	0
6	0
ng	0
/	0
mg	0
prot	0
)	0
than	0
jJ	0
rats	0
(	0
15	0
+	0
/	0
-	0
3	0
)	0
(	0
p	0
less	0
than	0
0	0
.	0
01	0
)	0
.	0

Aspirin	1
treatment	0
reduced	0
PGE2	1
synthesis	0
in	0
all	0
regions	0
,	0
but	0
outer	0
medullary	0
PGE2	1
remained	0
higher	0
in	0
jj	0
(	0
18	0
+	0
/	0
-	0
3	0
)	0
than	0
jJ	0
rats	0
(	0
9	0
+	0
/	0
-	0
2	0
)	0
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

PGF2	1
alpha	2
was	0
also	0
significantly	0
higher	0
in	0
the	0
outer	0
medulla	0
of	0
jj	0
rats	0
with	0
and	0
without	0
aspirin	1
administration	0
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

The	0
changes	0
in	0
renal	0
prostaglandin	1
synthesis	0
were	0
accompanied	0
by	0
evidence	0
of	0
renal	3
damage	4
in	0
aspirin	1
-	0
treated	0
jj	0
but	0
not	0
jJ	0
rats	0
as	0
evidenced	0
by	0
:	0
increased	0
incidence	0
and	0
severity	0
of	0
hematuria	3
(	0
p	0
less	0
than	0
0	0
.	0
01	0
)	0
;	0
increased	0
serum	0
creatinine	1
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
;	0
and	0
increase	0
in	0
outer	0
medullary	0
histopathologic	0
lesions	0
(	0
p	0
less	0
than	0
0	0
.	0
005	0
compared	0
to	0
either	0
sham	0
-	0
treated	0
jj	0
or	0
aspirin	1
-	0
treated	0
jJ	0
)	0
.	0

These	0
results	0
suggest	0
that	0
enhanced	0
prostaglandin	1
synthesis	0
contributes	0
to	0
maintenance	0
of	0
renal	0
function	0
and	0
morphological	0
integrity	0
,	0
and	0
that	0
inhibition	0
of	0
prostaglandin	1
synthesis	0
may	0
lead	0
to	0
pathological	3
renal	4
medullary	4
lesions	4
and	0
deterioration	3
of	4
renal	4
function	4
.	0

Prophylactic	0
lidocaine	1
in	0
the	0
early	0
phase	0
of	0
suspected	0
myocardial	3
infarction	4
.	0

Four	0
hundred	0
two	0
patients	0
with	0
suspected	0
myocardial	3
infarction	4
seen	0
within	0
6	0
hours	0
of	0
the	0
onset	0
of	0
symptoms	0
entered	0
a	0
double	0
-	0
blind	0
randomized	0
trial	0
of	0
lidocaine	1
vs	0
placebo	0
.	0

During	0
the	0
1	0
hour	0
after	0
administration	0
of	0
the	0
drug	0
the	0
incidence	0
of	0
ventricular	3
fibrillation	4
or	0
sustained	0
ventricular	3
tachycardia	4
among	0
the	0
204	0
patients	0
with	0
acute	0
myocardial	3
infarction	4
was	0
low	0
,	0
1	0
.	0
5	0
%	0
.	0

Lidocaine	1
,	0
given	0
in	0
a	0
300	0
mg	0
dose	0
intramuscularly	0
followed	0
by	0
100	0
mg	0
intravenously	0
,	0
did	0
not	0
prevent	0
sustained	0
ventricular	3
tachycardia	4
,	0
although	0
there	0
was	0
a	0
significant	0
reduction	0
in	0
the	0
number	0
of	0
patients	0
with	0
warning	0
arrhythmias	3
between	0
15	0
and	0
45	0
minutes	0
after	0
the	0
administration	0
of	0
lidocaine	1
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

The	0
average	0
plasma	0
lidocaine	1
level	0
10	0
minutes	0
after	0
administration	0
for	0
patients	0
without	0
a	0
myocardial	3
infarction	4
was	0
significantly	0
higher	0
than	0
that	0
for	0
patients	0
with	0
an	0
acute	0
infarction	3
.	0

The	0
mean	0
plasma	0
lidocaine	1
level	0
of	0
patients	0
on	0
beta	0
-	0
blocking	0
agents	0
was	0
no	0
different	0
from	0
that	0
in	0
patients	0
not	0
on	0
beta	0
blocking	0
agents	0
.	0

During	0
the	0
1	0
-	0
hour	0
study	0
period	0
,	0
the	0
incidence	0
of	0
central	0
nervous	0
system	0
side	0
effects	0
was	0
significantly	0
greater	0
in	0
the	0
lidocaine	1
group	0
,	0
hypotension	3
occurred	0
in	0
11	0
patients	0
,	0
nine	0
of	0
whom	0
had	0
received	0
lidocaine	1
,	0
and	0
four	0
patients	0
died	0
from	0
asystole	3
,	0
three	0
of	0
whom	0
had	0
had	0
lidocaine	1
.	0

We	0
cannot	0
advocate	0
the	0
administration	0
of	0
lidocaine	1
prophylactically	0
in	0
the	0
early	0
hours	0
of	0
suspected	0
myocardial	3
infarction	4
.	0

Evidence	0
for	0
a	0
cholinergic	0
role	0
in	0
haloperidol	1
-	0
induced	0
catalepsy	3
.	0

Experiments	0
in	0
mice	0
tested	0
previous	0
evidence	0
that	0
activation	0
of	0
cholinergic	0
systems	0
promotes	0
catalepsy	3
and	0
that	0
cholinergic	0
mechanisms	0
need	0
to	0
be	0
intact	0
for	0
full	0
expression	0
of	0
neuroleptic	1
-	0
induced	0
catalepsy	3
.	0

Large	0
doses	0
of	0
the	0
cholinomimetic	0
,	0
pilocarpine	1
,	0
could	0
induce	0
catalepsy	3
when	0
peripheral	0
cholinergic	0
receptors	0
were	0
blocked	0
.	0

Low	0
doses	0
of	0
pilocarpine	1
caused	0
a	0
pronounced	0
enhancement	0
of	0
the	0
catalepsy	3
that	0
was	0
induced	0
by	0
the	0
dopaminergic	0
blocker	0
,	0
haloperidol	1
.	0

A	0
muscarinic	0
receptor	0
blocker	0
,	0
atropine	1
,	0
disrupted	0
haloperidol	1
-	0
induced	0
catalepsy	3
.	0

Intracranial	0
injection	0
of	0
an	0
acetylcholine	1
-	0
synthesis	0
inhibitor	0
,	0
hemicholinium	1
,	0
prevented	0
the	0
catalepsy	3
that	0
is	0
usually	0
induced	0
by	0
haloperidol	1
.	0

These	0
findings	0
suggest	0
the	0
hypothesis	0
that	0
the	0
catalepsy	3
that	0
is	0
produced	0
by	0
neuroleptics	1
such	0
as	0
haloperidol	1
is	0
actually	0
mediated	0
by	0
intrinsic	0
central	0
cholinergic	0
systems	0
.	0

Alternatively	0
,	0
activation	0
of	0
central	0
cholinergic	0
systems	0
could	0
promote	0
catalepsy	3
by	0
suppression	0
of	0
dopaminergic	0
systems	0
.	0

Cardiovascular	3
dysfunction	4
and	0
hypersensitivity	3
to	0
sodium	1
pentobarbital	2
induced	0
by	0
chronic	0
barium	1
chloride	2
ingestion	0
.	0

Barium	1
-	0
supplemented	0
Long	0
-	0
Evans	0
hooded	0
rats	0
were	0
characterized	0
by	0
a	0
persistent	0
hypertension	3
that	0
was	0
evident	0
after	0
1	0
month	0
of	0
barium	1
(	0
100	0
micrograms	0
/	0
ml	0
mineral	0
fortified	0
water	0
)	0
treatment	0
.	0

Analysis	0
of	0
in	0
vivo	0
myocardial	0
excitability	0
,	0
contractility	0
,	0
and	0
metabolic	0
characteristics	0
at	0
16	0
months	0
revealed	0
other	0
significant	0
barium	1
-	0
induced	0
disturbances	3
within	4
the	4
cardiovascular	4
system	4
.	0

The	0
most	0
distinctive	0
aspect	0
of	0
the	0
barium	1
effect	0
was	0
a	0
demonstrated	0
hypersensitivity	3
of	0
the	0
cardiovascular	0
system	0
to	0
sodium	1
pentobarbital	2
.	0

Under	0
barbiturate	1
anesthesia	0
,	0
virtually	0
all	0
of	0
the	0
myocardial	0
contractile	0
indices	0
were	0
depressed	0
significantly	0
in	0
barium	1
-	0
exposed	0
rats	0
relative	0
to	0
the	0
corresponding	0
control	0
-	0
fed	0
rats	0
.	0

The	0
lack	0
of	0
a	0
similar	0
response	0
to	0
ketamine	1
and	0
xylazine	1
anesthesia	0
revealed	0
that	0
the	0
cardiovascular	0
actions	0
of	0
sodium	1
pentobarbital	2
in	0
barium	1
-	0
treated	0
rats	0
were	0
linked	0
specifically	0
to	0
this	0
anesthetic	0
,	0
and	0
were	0
not	0
representative	0
of	0
a	0
generalized	0
anesthetic	0
response	0
.	0

0ther	0
myocardial	0
pathophysiologic	0
and	0
metabolic	0
changes	0
induced	0
by	0
barium	1
were	0
manifest	0
,	0
irrespective	0
of	0
the	0
anesthetic	0
employed	0
.	0

The	0
contractile	0
element	0
shortening	0
velocity	0
of	0
the	0
cardiac	0
muscle	0
fibers	0
was	0
significantly	0
slower	0
in	0
both	0
groups	0
of	0
barium	1
-	0
treated	0
rats	0
relative	0
to	0
the	0
control	0
groups	0
,	0
irrespective	0
of	0
the	0
anesthetic	0
regimen	0
.	0

Similarly	0
,	0
significant	0
disturbances	0
in	0
myocardial	0
energy	0
metabolism	0
were	0
detected	0
in	0
the	0
barium	1
-	0
exposed	0
rats	0
which	0
were	0
consistent	0
with	0
the	0
reduced	0
contractile	0
element	0
shortening	0
velocity	0
.	0

In	0
addition	0
,	0
the	0
excitability	0
of	0
the	0
cardiac	0
conduction	0
system	0
was	0
depressed	0
preferentially	0
in	0
the	0
atrioventricular	0
nodal	0
region	0
of	0
hearts	0
from	0
barium	1
-	0
exposed	0
rats	0
.	0

0verall	0
,	0
the	0
altered	0
cardiac	0
contractility	0
and	0
excitability	0
characteristics	0
,	0
the	0
myocardial	0
metabolic	3
disturbances	4
,	0
and	0
the	0
hypersensitivity	3
of	0
the	0
cardiovascular	0
system	0
to	0
sodium	1
pentobarbital	2
suggest	0
the	0
existence	0
of	0
a	0
heretofore	0
undescribed	0
cardiomyopathic	3
disorder	4
induced	0
by	0
chronic	0
barium	1
exposure	0
.	0

These	0
experimental	0
findings	0
represent	0
the	0
first	0
indication	0
that	0
life	0
-	0
long	0
barium	1
ingestion	0
may	0
have	0
significant	0
adverse	0
effects	0
on	0
the	0
mammalian	0
cardiovascular	0
system	0
.	0

Propranolol	1
antagonism	0
of	0
phenylpropanolamine	1
-	0
induced	0
hypertension	3
.	0

Phenylpropanolamine	1
(	0
PPA	1
)	0
overdose	3
can	0
cause	0
severe	0
hypertension	3
,	0
intracerebral	3
hemorrhage	4
,	0
and	0
death	0
.	0

We	0
studied	0
the	0
efficacy	0
and	0
safety	0
of	0
propranolol	1
in	0
the	0
treatment	0
of	0
PPA	1
-	0
induced	0
hypertension	3
.	0

Subjects	0
received	0
propranolol	1
either	0
by	0
mouth	0
for	0
48	0
hours	0
before	0
PPA	1
or	0
as	0
a	0
rapid	0
intravenous	0
infusion	0
after	0
PPA	1
.	0

PPA	1
,	0
75	0
mg	0
alone	0
,	0
increased	0
blood	0
pressure	0
(	0
31	0
+	0
/	0
-	0
14	0
mm	0
Hg	0
systolic	0
,	0
20	0
+	0
/	0
-	0
5	0
mm	0
Hg	0
diastolic	0
)	0
,	0
and	0
propranolol	1
pretreatment	0
antagonized	0
this	0
increase	0
(	0
12	0
+	0
/	0
-	0
10	0
mm	0
Hg	0
systolic	0
,	0
10	0
+	0
/	0
-	0
7	0
mm	0
Hg	0
diastolic	0
)	0
.	0

Intravenous	0
propranolol	1
after	0
PPA	1
also	0
decreased	0
blood	0
pressure	0
.	0

Left	0
ventricular	0
function	0
(	0
assessed	0
by	0
echocardiography	0
)	0
showed	0
that	0
PPA	1
increased	0
the	0
stroke	3
volume	0
30	0
%	0
(	0
from	0
62	0
.	0
5	0
+	0
/	0
-	0
20	0
.	0
9	0
to	0
80	0
.	0
8	0
+	0
/	0
-	0
22	0
.	0
4	0
ml	0
)	0
,	0
the	0
ejection	0
fraction	0
9	0
%	0
(	0
from	0
64	0
%	0
+	0
/	0
-	0
10	0
%	0
to	0
70	0
%	0
+	0
/	0
-	0
7	0
%	0
)	0
,	0
and	0
cardiac	0
output	0
14	0
%	0
(	0
from	0
3	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
6	0
to	0
4	0
.	0
1	0
+	0
/	0
-	0
1	0
.	0
0	0
L	0
/	0
min	0
)	0
.	0

Intravenous	0
propranolol	1
reversed	0
these	0
effects	0
.	0

Systemic	0
vascular	0
resistance	0
was	0
increased	0
by	0
PPA	1
28	0
%	0
(	0
from	0
1710	0
+	0
/	0
-	0
200	0
to	0
2190	0
+	0
/	0
-	0
700	0
dyne	0
X	0
sec	0
/	0
cm5	0
)	0
and	0
was	0
further	0
increased	0
by	0
propranolol	1
22	0
%	0
(	0
to	0
2660	0
+	0
/	0
-	0
1200	0
dyne	0
X	0
sec	0
/	0
cm5	0
)	0
.	0

We	0
conclude	0
that	0
PPA	1
increases	0
blood	0
pressure	0
by	0
increasing	0
systemic	0
vascular	0
resistance	0
and	0
cardiac	0
output	0
,	0
and	0
that	0
propranolol	1
antagonizes	0
this	0
increase	0
by	0
reversing	0
the	0
effect	0
of	0
PPA	1
on	0
cardiac	0
output	0
.	0

That	0
propranolol	1
antagonizes	0
the	0
pressor	0
effect	0
of	0
PPA	1
is	0
in	0
contrast	0
to	0
the	0
interaction	0
in	0
which	0
propranolol	1
enhances	0
the	0
pressor	0
effect	0
of	0
norepinephrine	1
.	0

This	0
is	0
probably	0
because	0
PPA	1
has	0
less	0
beta	0
2	0
activity	0
than	0
does	0
norepinephrine	1
.	0

Mesangial	0
function	0
and	0
glomerular	3
sclerosis	4
in	0
rats	0
with	0
aminonucleoside	1
nephrosis	3
.	0

The	0
possible	0
relationship	0
between	0
mesangial	3
dysfunction	4
and	0
development	0
of	0
glomerular	3
sclerosis	4
was	0
studied	0
in	0
the	0
puromycin	1
aminonucleoside	2
(	0
PAN	1
)	0
model	0
.	0

Five	0
male	0
Wistar	0
rats	0
received	0
repeated	0
subcutaneous	0
PAN	1
injections	0
;	0
five	0
controls	0
received	0
saline	0
only	0
.	0

After	0
4	0
weeks	0
the	0
PAN	1
rats	0
were	0
severely	0
proteinuric	3
(	0
190	0
+	0
/	0
-	0
80	0
mg	0
/	0
24	0
hr	0
)	0
,	0
and	0
all	0
rats	0
were	0
given	0
colloidal	0
carbon	1
(	0
CC	0
)	0
intravenously	0
.	0

At	0
5	0
months	0
glomerular	3
sclerosis	4
was	0
found	0
in	0
7	0
.	0
6	0
+	0
/	0
-	0
3	0
.	0
4	0
%	0
of	0
the	0
glomeruli	0
of	0
PAN	1
rats	0
;	0
glomeruli	0
of	0
the	0
controls	0
were	0
normal	0
.	0

Glomeruli	0
of	0
PAN	1
rats	0
contained	0
significantly	0
more	0
CC	0
than	0
glomeruli	0
of	0
controls	0
.	0

Glomeruli	0
with	0
sclerosis	3
contained	0
significantly	0
more	0
CC	0
than	0
non	0
-	0
sclerotic	0
glomeruli	0
in	0
the	0
same	0
kidneys	0
.	0

CC	0
was	0
preferentially	0
localized	0
within	0
the	0
sclerotic	0
areas	0
of	0
the	0
affected	0
glomeruli	0
.	0

Since	0
mesangial	0
CC	0
clearance	0
from	0
the	0
mesangium	0
did	0
not	0
change	0
during	0
chronic	0
PAN	1
treatment	0
,	0
we	0
conclude	0
that	0
this	0
preferential	0
CC	0
localization	0
within	0
the	0
lesions	0
is	0
caused	0
by	0
an	0
increased	0
CC	0
uptake	0
shortly	0
after	0
injection	0
in	0
apparent	0
vulnerable	0
areas	0
where	0
sclerosis	3
will	0
develop	0
subsequently	0
.	0

Cluster	0
analysis	0
showed	0
a	0
random	0
distribution	0
of	0
lesions	0
in	0
the	0
PAN	1
glomeruli	0
in	0
concordance	0
with	0
the	0
random	0
localization	0
of	0
mesangial	0
areas	0
with	0
dysfunction	0
in	0
this	0
model	0
.	0

Similar	0
to	0
the	0
remnant	0
kidney	0
model	0
in	0
PAN	1
nephrosis	3
the	0
development	0
of	0
glomerular	3
sclerosis	4
may	0
be	0
related	0
to	0
"	0
mesangial	0
overloading	0
.	0
"	0

Relationship	0
between	0
nicotine	1
-	0
induced	0
seizures	3
and	0
hippocampal	0
nicotinic	0
receptors	0
.	0

A	0
controversy	0
has	0
existed	0
for	0
several	0
years	0
concerning	0
the	0
physiological	0
relevance	0
of	0
the	0
nicotinic	0
receptor	0
measured	0
by	0
alpha	0
-	0
bungarotoxin	0
binding	0
.	0

Using	0
mice	0
derived	0
from	0
a	0
classical	0
F2	0
and	0
backcross	0
genetic	0
design	0
,	0
a	0
relationship	0
between	0
nicotine	1
-	0
induced	0
seizures	3
and	0
alpha	0
-	0
bungarotoxin	0
nicotinic	0
receptor	0
concentration	0
was	0
found	0
.	0

Mice	0
sensitive	0
to	0
the	0
convulsant	0
effects	0
of	0
nicotine	1
had	0
greater	0
alpha	0
-	0
bungarotoxin	0
binding	0
in	0
the	0
hippocampus	0
than	0
seizure	3
insensitive	0
mice	0
.	0

The	0
binding	0
sites	0
from	0
seizure	3
sensitive	0
and	0
resistant	0
mice	0
were	0
equally	0
affected	0
by	0
treatment	0
with	0
dithiothreitol	1
,	0
trypsin	0
or	0
heat	0
.	0

Thus	0
it	0
appears	0
that	0
the	0
difference	0
between	0
seizure	3
sensitive	0
and	0
insensitive	0
animals	0
may	0
be	0
due	0
to	0
a	0
difference	0
in	0
hippocampal	0
nicotinic	0
receptor	0
concentration	0
as	0
measured	0
with	0
alpha	0
-	0
bungarotoxin	0
binding	0
.	0

The	0
role	0
of	0
p	1
-	2
aminophenol	2
in	0
acetaminophen	1
-	0
induced	0
nephrotoxicity	3
:	0
effect	0
of	0
bis	1
(	2
p	2
-	2
nitrophenyl	2
)	2
phosphate	2
on	0
acetaminophen	1
and	0
p	1
-	2
aminophenol	2
nephrotoxicity	3
and	0
metabolism	0
in	0
Fischer	0
344	0
rats	0
.	0

Acetaminophen	1
(	0
APAP	1
)	0
produces	0
proximal	0
tubular	3
necrosis	4
in	0
Fischer	0
344	0
(	0
F344	0
)	0
rats	0
.	0

Recently	0
,	0
p	1
-	2
aminophenol	2
(	0
PAP	1
)	0
,	0
a	0
known	0
potent	0
nephrotoxicant	0
,	0
was	0
identified	0
as	0
a	0
metabolite	0
of	0
APAP	1
in	0
F344	0
rats	0
.	0

The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
determine	0
if	0
PAP	1
formation	0
is	0
a	0
requisite	0
step	0
in	0
APAP	1
-	0
induced	0
nephrotoxicity	3
.	0

Therefore	0
,	0
the	0
effect	0
of	0
bis	1
(	2
p	2
-	2
nitrophenyl	2
)	2
phosphate	2
(	0
BNPP	1
)	0
,	0
an	0
acylamidase	0
inhibitor	0
,	0
on	0
APAP	1
and	0
PAP	1
nephrotoxicity	3
and	0
metabolism	0
was	0
determined	0
.	0

BNPP	1
(	0
1	0
to	0
8	0
mM	0
)	0
reduced	0
APAP	1
deacetylation	0
and	0
covalent	0
binding	0
in	0
F344	0
renal	0
cortical	0
homogenates	0
in	0
a	0
concentration	0
-	0
dependent	0
manner	0
.	0

Pretreatment	0
of	0
animals	0
with	0
BNPP	1
prior	0
to	0
APAP	1
or	0
PAP	1
administration	0
resulted	0
in	0
marked	0
reduction	0
of	0
APAP	1
(	0
900	0
mg	0
/	0
kg	0
)	0
nephrotoxicity	3
but	0
not	0
PAP	1
nephrotoxicity	3
.	0

This	0
result	0
was	0
not	0
due	0
to	0
altered	0
disposition	0
of	0
either	0
APAP	1
or	0
acetylated	0
metabolites	0
in	0
plasma	0
or	0
renal	0
cortical	0
and	0
hepatic	0
tissue	0
.	0

Rather	0
,	0
BNPP	1
pretreatment	0
reduced	0
the	0
fraction	0
of	0
APAP	1
excreted	0
as	0
PAP	1
by	0
64	0
and	0
75	0
%	0
after	0
APAP	1
doses	0
of	0
750	0
and	0
900	0
mg	0
/	0
kg	0
.	0

BNPP	1
did	0
not	0
alter	0
the	0
excretion	0
of	0
APAP	1
or	0
any	0
of	0
its	0
non	0
-	0
deacetylated	0
metabolites	0
nor	0
did	0
BNPP	1
alter	0
excretion	0
of	0
PAP	1
or	0
its	0
metabolites	0
after	0
PAP	1
doses	0
of	0
150	0
and	0
300	0
mg	0
/	0
kg	0
.	0

Therefore	0
,	0
the	0
BNPP	1
-	0
induced	0
reduction	0
in	0
APAP	1
-	0
induced	0
nephrotoxicity	3
appears	0
to	0
be	0
due	0
to	0
inhibition	0
of	0
APAP	1
deacetylation	0
.	0

It	0
is	0
concluded	0
that	0
PAP	1
formation	0
,	0
in	0
vivo	0
,	0
accounts	0
,	0
at	0
least	0
in	0
part	0
,	0
for	0
APAP	1
-	0
induced	0
renal	3
tubular	4
necrosis	4
.	0

Morphine	1
-	0
induced	0
seizures	3
in	0
newborn	0
infants	0
.	0

Two	0
neonates	0
suffered	0
from	0
generalized	0
seizures	3
during	0
the	0
course	0
of	0
intravenous	0
morphine	1
sulfate	2
for	0
post	0
-	0
operative	0
analgesia	0
.	0

They	0
received	0
morphine	1
in	0
doses	0
of	0
32	0
micrograms	0
/	0
kg	0
/	0
hr	0
and	0
40	0
micrograms	0
/	0
kg	0
/	0
hr	0
larger	0
than	0
a	0
group	0
of	0
10	0
neonates	0
who	0
received	0
6	0
-	0
24	0
micrograms	0
/	0
kg	0
/	0
hr	0
and	0
had	0
no	0
seizures	3
.	0

Plasma	0
concentrations	0
of	0
morphine	1
in	0
these	0
neonates	0
was	0
excessive	0
(	0
60	0
and	0
90	0
mg	0
/	0
ml	0
)	0
.	0

0ther	0
known	0
reasons	0
for	0
seizures	3
were	0
ruled	0
out	0
and	0
the	0
convulsions	3
stopped	0
a	0
few	0
hours	0
after	0
cessation	0
of	0
morphine	1
and	0
did	0
not	0
reoccur	0
in	0
the	0
subsequent	0
8	0
months	0
.	0

It	0
is	0
suggested	0
that	0
post	0
-	0
operative	0
intravenous	0
morphine	1
should	0
not	0
exceed	0
20	0
micrograms	0
/	0
kg	0
/	0
ml	0
in	0
neonates	0
.	0

Indomethacin	1
induced	0
hypotension	3
in	0
sodium	1
and	0
volume	0
depleted	0
rats	0
.	0

After	0
a	0
single	0
oral	0
dose	0
of	0
4	0
mg	0
/	0
kg	0
indomethacin	1
(	0
IDM	1
)	0
to	0
sodium	1
and	0
volume	0
depleted	0
rats	0
plasma	0
renin	0
activity	0
(	0
PRA	0
)	0
and	0
systolic	0
blood	0
pressure	0
fell	0
significantly	0
within	0
four	0
hours	0
.	0

In	0
sodium	1
repleted	0
animals	0
indomethacin	1
did	0
not	0
change	0
systolic	0
blood	0
pressure	0
(	0
BP	0
)	0
although	0
plasma	0
renin	0
activity	0
was	0
decreased	0
.	0

Thus	0
,	0
indomethacin	1
by	0
inhibition	0
of	0
prostaglandin	1
synthesis	0
may	0
diminish	0
the	0
blood	0
pressure	0
maintaining	0
effect	0
of	0
the	0
stimulated	0
renin	0
-	0
angiotensin	1
system	0
in	0
sodium	1
and	0
volume	0
depletion	0
.	0

0n	0
the	0
antiarrhythmic	0
activity	0
of	0
one	0
N	0
-	0
substituted	0
piperazine	1
derivative	0
of	0
trans	1
-	2
2	2
-	2
amino	2
-	2
3	2
-	2
hydroxy	2
-	2
1	2
,	2
2	2
,	2
3	2
,	2
4	2
-	2
tetrahydroanaphthalene	2
.	0

The	0
antiarrhythmic	0
activity	0
of	0
the	0
compound	0
N	1
-	2
(	2
trans	2
-	2
3	2
-	2
hydroxy	2
-	2
1	2
,	2
2	2
,	2
3	2
,	2
4	2
-	2
tetrahydro	2
-	2
2	2
-	2
naphthyl	2
)	2
-	2
N	2
-	2
(	2
3	2
-	2
oxo	2
-	2
3	2
-	2
phenyl	2
-	2
2	2
-	2
methylpropyl	2
)	2
-	2
piperazine	2
hydrochloride	2
,	0
referred	0
to	0
as	0
P11	1
,	0
is	0
studied	0
on	0
anaesthesized	0
cats	0
and	0
Wistar	0
albino	0
rats	0
,	0
as	0
well	0
as	0
on	0
non	0
-	0
anaesthesized	0
rabbits	0
.	0

Four	0
types	0
of	0
experimental	0
arrhythmia	3
are	0
used	0
-	0
-	0
with	0
BaCl2	1
,	0
with	0
chloroform	1
-	0
adrenaline	1
,	0
with	0
strophantine	1
G	2
and	0
with	0
aconitine	1
.	0

The	0
compound	0
P11	1
is	0
introduced	0
in	0
doses	0
of	0
0	0
.	0
25	0
and	0
0	0
.	0
50	0
mg	0
/	0
kg	0
intravenously	0
and	0
10	0
mg	0
/	0
kg	0
orally	0
.	0

The	0
compound	0
manifests	0
antiarrhythmic	0
activity	0
in	0
all	0
models	0
of	0
experimental	0
arrhythmia	3
used	0
,	0
causing	0
greatest	0
inhibition	0
on	0
the	0
arrhythmia	3
induced	0
by	0
chloroform	1
-	0
adrenaline	1
(	0
in	0
90	0
per	0
cent	0
)	0
and	0
with	0
BaCl2	1
(	0
in	0
84	0
per	0
cent	0
)	0
.	0

The	0
results	0
obtained	0
are	0
associated	0
with	0
the	0
beta	0
-	0
adrenoblocking	0
and	0
with	0
the	0
membrane	0
-	0
stabilizing	0
action	0
of	0
the	0
compound	0
.	0

Recurrent	0
subarachnoid	3
hemorrhage	4
associated	0
with	0
aminocaproic	1
acid	2
therapy	0
and	0
acute	3
renal	4
artery	4
thrombosis	4
.	0

Case	0
report	0
.	0

Epsilon	1
aminocaproic	2
acid	2
(	0
EACA	1
)	0
has	0
been	0
used	0
to	0
prevent	0
rebleeding	0
in	0
patients	0
with	0
subarachnoid	3
hemorrhage	4
(	0
SAH	3
)	0
.	0

Although	0
this	0
agent	0
does	0
decrease	0
the	0
frequency	0
of	0
rebleeding	0
,	0
several	0
reports	0
have	0
described	0
thrombotic	3
complications	0
of	0
EACA	1
therapy	0
.	0

These	0
complications	0
have	0
included	0
clinical	0
deterioration	0
and	0
intracranial	3
vascular	4
thrombosis	4
in	0
patients	0
with	0
SAH	3
,	0
arteriolar	0
and	0
capillary	0
fibrin	0
thrombi	3
in	0
patients	0
with	0
fibrinolytic	0
syndromes	0
treated	0
with	0
EACA	1
,	0
or	0
other	0
thromboembolic	3
phenomena	4
.	0

Since	0
intravascular	0
fibrin	0
thrombi	3
are	0
often	0
observed	0
in	0
patients	0
with	0
fibrinolytic	0
disorders	0
,	0
EACA	1
should	0
not	0
be	0
implicated	0
in	0
the	0
pathogenesis	0
of	0
fibrin	0
thrombi	3
in	0
patients	0
with	0
disseminated	3
intravascular	4
coagulation	4
or	0
other	0
"	0
consumption	3
coagulopathies	4
.	0
"	0
This	0
report	0
describes	0
subtotal	0
infarction	3
of	0
the	0
kidney	0
due	0
to	0
thrombosis	3
of	4
a	4
normal	4
renal	4
artery	4
.	0

This	0
occlusion	0
occurred	0
after	0
EACA	1
therapy	0
in	0
a	0
patient	0
with	0
SAH	3
and	0
histopathological	0
documentation	0
of	0
recurrent	0
SAH	3
.	0

The	0
corresponding	0
clinical	0
event	0
was	0
characterized	0
by	0
marked	0
hypertension	3
and	0
abrupt	0
neurological	0
deterioration	0
.	0

Effect	0
of	0
vincristine	1
sulfate	2
on	0
Pseudomonas	3
infections	4
in	0
monkeys	0
.	0

In	0
rhesus	0
monkeys	0
,	0
intravenous	0
challenge	0
with	0
0	0
.	0
6	0
x	0
10	0
(	0
10	0
)	0
to	0
2	0
.	0
2	0
x	0
10	0
(	0
10	0
)	0
Pseudomonas	0
aeruginosa	0
organisms	0
caused	0
acute	0
illness	0
of	0
4	0
to	0
5	0
days	0
'	0
duration	0
with	0
spontaneous	0
recovery	0
in	0
13	0
of	0
15	0
monkeys	0
;	0
blood	0
cultures	0
became	0
negative	0
3	0
to	0
17	0
days	0
after	0
challenge	0
.	0

Leukocytosis	3
was	0
observed	0
in	0
all	0
monkeys	0
.	0

Intravenous	0
or	0
intratracheal	0
inoculation	0
of	0
2	0
.	0
0	0
to	0
2	0
.	0
5	0
mg	0
of	0
vincristine	1
sulfate	2
was	0
followed	0
by	0
leukopenia	3
in	0
4	0
to	0
5	0
days	0
.	0

Intravenous	0
inoculation	0
of	0
4	0
.	0
2	0
x	0
10	0
(	0
10	0
)	0
to	0
7	0
.	0
8	0
x	0
10	0
(	0
10	0
)	0
pyocin	0
type	0
6	0
Pseudomonas	0
organisms	0
in	0
monkeys	0
given	0
vincristine	1
sulfate	2
4	0
days	0
previously	0
resulted	0
in	0
fatal	0
infection	3
in	0
11	0
of	0
14	0
monkeys	0
,	0
whereas	0
none	0
of	0
four	0
receiving	0
Pseudomonas	0
alone	0
died	0
.	0

These	0
studies	0
suggest	0
that	0
an	0
antimetabolite	0
-	0
induced	0
leukopenia	3
predisposes	0
to	0
severe	0
Pseudomonas	0
sepsis	3
and	0
that	0
such	0
monkeys	0
may	0
serve	0
as	0
a	0
biological	0
model	0
for	0
study	0
of	0
comparative	0
efficacy	0
of	0
antimicrobial	0
agents	0
.	0

Modification	0
by	0
propranolol	1
of	0
cardiovascular	0
effects	0
of	0
induced	0
hypoglycaemia	3
.	0

The	0
cardiovascular	0
effects	0
of	0
hypoglycaemia	3
,	0
with	0
and	0
without	0
beta	0
-	0
blockade	0
,	0
were	0
compared	0
in	0
fourteen	0
healthy	0
men	0
.	0

Eight	0
received	0
insulin	0
alone	0
,	0
and	0
eight	0
,	0
including	0
two	0
of	0
the	0
original	0
insulin	0
-	0
only	0
group	0
,	0
were	0
given	0
propranolol	1
and	0
insulin	0
.	0

In	0
the	0
insulin	0
-	0
group	0
the	0
period	0
of	0
hypoglycaemia	3
was	0
associated	0
with	0
an	0
increase	0
in	0
heart	0
-	0
rate	0
and	0
a	0
fall	0
in	0
diastolic	0
blood	0
-	0
pressure	0
.	0

In	0
the	0
propranolol	1
-	0
insulin	0
group	0
there	0
was	0
a	0
significant	0
fall	0
in	0
heart	0
-	0
rate	0
in	0
most	0
subjects	0
and	0
an	0
increase	0
in	0
diastolic	0
pressure	0
.	0

Typical	0
S	0
-	0
T	0
/	0
T	0
changes	0
occurred	0
in	0
the	0
insulin	0
-	0
group	0
but	0
in	0
none	0
of	0
the	0
propranolol	1
-	0
insulin	0
group	0
.	0

Hypertension	3
in	0
diabetics	3
prone	0
to	0
hypoglycaemia	3
attacks	0
should	0
not	0
be	0
treated	0
with	0
beta	0
-	0
blockers	0
because	0
these	0
drugs	0
may	0
cause	0
a	0
sharp	0
rise	0
in	0
blood	0
-	0
pressure	0
in	0
such	0
patients	0
.	0

Long	0
-	0
term	0
propranolol	1
therapy	0
in	0
pregnancy	0
:	0
maternal	0
and	0
fetal	0
outcome	0
.	0

Propranolol	1
,	0
a	0
beta	0
-	0
adrenergic	0
blocking	0
agent	0
,	0
has	0
found	0
an	0
important	0
position	0
in	0
the	0
practice	0
of	0
medicine	0
.	0

Its	0
use	0
in	0
pregnancy	0
,	0
however	0
,	0
is	0
an	0
open	0
question	0
as	0
a	0
number	0
of	0
detrimental	0
side	0
effects	0
have	0
been	0
reported	0
in	0
the	0
fetus	0
and	0
neonate	0
.	0

Ten	0
patients	0
and	0
12	0
pregnancies	0
are	0
reported	0
where	0
chronic	0
propranolol	1
has	0
been	0
administered	0
.	0

Five	0
patients	0
with	0
serial	0
pregnancies	0
with	0
and	0
without	0
propranolol	1
therapy	0
are	0
also	0
examined	0
.	0

Maternal	0
,	0
fetal	0
,	0
and	0
neonatal	0
complications	0
are	0
examined	0
.	0

An	0
attempt	0
is	0
made	0
to	0
differentiate	0
drug	0
-	0
related	0
complications	0
from	0
maternal	0
disease	0
-	0
-	0
related	0
complications	0
.	0

We	0
conclude	0
that	0
previously	0
reported	0
hypoglycemia	3
,	0
hyperbilirubinemia	3
,	0
polycythemia	3
,	0
neonatal	3
apnea	4
,	0
and	0
bradycardia	3
are	0
not	0
invariable	0
and	0
cannot	0
be	0
statistically	0
correlated	0
with	0
chronic	0
propranolol	1
therapy	0
.	0

Growth	3
retardation	4
,	0
however	0
,	0
appears	0
to	0
be	0
significant	0
in	0
both	0
of	0
our	0
series	0
.	0

Central	0
excitatory	0
actions	0
of	0
flurazepam	1
.	0

Toxic	0
actions	0
of	0
flurazepam	1
(	0
FZP	1
)	0
were	0
studied	0
in	0
cats	0
,	0
mice	0
and	0
rats	0
.	0

High	0
doses	0
caused	0
an	0
apparent	0
central	0
excitation	0
,	0
most	0
clearly	0
seen	0
as	0
clonic	0
convulsions	3
,	0
superimposed	0
on	0
general	0
depression	3
.	0

Following	0
a	0
lethal	0
dose	0
,	0
death	0
was	0
always	0
associated	0
with	0
convulsions	3
.	0

Comparing	0
the	0
relative	0
sensitivity	0
to	0
central	0
depression	3
and	0
excitation	0
revealed	0
that	0
rats	0
were	0
least	0
likely	0
to	0
have	0
convulsions	3
at	0
doses	0
that	0
did	0
not	0
first	0
cause	0
loss	3
of	4
consciousness	4
,	0
while	0
cats	0
most	0
clearly	0
showed	0
marked	0
central	0
excitatory	0
actions	0
.	0

Signs	0
of	0
FZP	1
toxocity	3
in	0
cats	0
included	0
excessive	0
salivation	3
,	0
extreme	0
apprehensive	0
behavior	0
,	0
retching	0
,	0
muscle	3
tremors	4
and	0
convulsions	3
.	0

An	0
interaction	0
between	0
FZP	1
and	0
pentylenetetrazol	1
(	0
PTZ	1
)	0
was	0
shown	0
by	0
pretreating	0
mice	0
with	0
FZP	1
before	0
PTZ	1
challenge	0
.	0

As	0
a	0
function	0
of	0
dose	0
,	0
FZP	1
first	0
protected	0
against	0
convulsions	3
and	0
death	0
.	0

At	0
higher	0
doses	0
,	0
however	0
,	0
convulsions	3
again	0
emerged	0
.	0

These	0
doses	0
of	0
FZP	1
were	0
lower	0
than	0
those	0
that	0
would	0
alone	0
cause	0
convulsions	3
.	0

These	0
results	0
may	0
be	0
relevant	0
to	0
the	0
use	0
of	0
FZP	1
in	0
clinical	0
situations	0
in	0
which	0
there	0
is	0
increased	0
neural	0
excitability	0
,	0
such	0
as	0
epilepsy	3
or	0
sedative	0
-	0
hypnotic	0
drug	0
withdrawal	0
.	0

Use	0
of	0
propranolol	1
in	0
the	0
treatment	0
of	0
idiopathic	3
orthostatic	4
hypotension	4
.	0

Five	0
patients	0
with	0
idiopathic	3
orthostatic	4
hypotension	4
who	0
had	0
physiologic	0
and	0
biochemical	0
evidence	0
of	0
severe	0
autonomic	0
dysfunction	0
were	0
included	0
in	0
the	0
study	0
.	0

They	0
all	0
exhibited	0
markedly	0
reduced	0
plasma	0
catecholamines	1
and	0
plasma	0
renin	0
activity	0
in	0
both	0
recumbent	0
and	0
upright	0
positions	0
and	0
had	0
marked	0
hypersensitivity	3
to	0
the	0
pressor	0
effects	0
of	0
infused	0
norepinephrine	1
.	0

Treatment	0
with	0
propanolol	1
administered	0
intravenously	0
(	0
1	0
-	0
5	0
mg	0
)	0
produced	0
increases	0
in	0
supine	0
and	0
upright	0
blood	0
pressure	0
in	0
4	0
of	0
the	0
5	0
individuals	0
with	0
rises	0
ranging	0
from	0
11	0
/	0
6	0
to	0
22	0
/	0
11	0
mmHg	0
.	0

Chronic	0
oral	0
administration	0
of	0
propranolol	1
(	0
40	0
-	0
160	0
mg	0
/	0
day	0
)	0
also	0
elevated	0
the	0
blood	0
pressures	0
of	0
these	0
individuals	0
with	0
increases	0
in	0
the	0
order	0
of	0
20	0
-	0
35	0
/	0
15	0
-	0
25	0
mmg	0
being	0
observed	0
.	0

In	0
1	0
patient	0
,	0
marked	0
hypertension	3
was	0
induced	0
by	0
propranolol	1
and	0
the	0
drug	0
had	0
to	0
be	0
withdrawn	0
.	0

It	0
otherwise	0
was	0
well	0
tolerated	0
and	0
no	0
important	0
side	0
effects	0
were	0
observed	0
.	0

Treatment	0
has	0
been	0
continued	0
in	0
3	0
individuals	0
for	0
6	0
-	0
13	0
months	0
with	0
persistence	0
of	0
the	0
pressor	0
effect	0
,	0
although	0
there	0
appears	0
to	0
have	0
been	0
some	0
decrease	0
in	0
the	0
degree	0
of	0
response	0
with	0
time	0
.	0

Hemodynamic	0
measurements	0
in	0
1	0
of	0
the	0
patients	0
demonstrated	0
an	0
increase	0
in	0
total	0
peripheral	0
resistance	0
and	0
essentially	0
no	0
change	0
in	0
cardiac	0
output	0
following	0
propranolol	1
therapy	0
.	0

The	0
studies	0
suggest	0
that	0
propranolol	1
is	0
a	0
useful	0
drug	0
in	0
selected	0
patients	0
with	0
severe	0
idiopathic	3
orthostatic	4
hypotension	4
.	0

Total	0
intravenous	0
anesthesia	0
with	0
etomidate	1
.	0

III	0
.	0

Some	0
observations	0
in	0
adults	0
.	0

An	0
investigation	0
was	0
undertaken	0
to	0
determine	0
the	0
dosage	0
of	0
etomidate	1
required	0
to	0
maintain	0
sleep	0
in	0
adults	0
undergoing	0
surgery	0
under	0
regional	0
local	0
anesthesia	0
.	0

Premedication	0
of	0
diazepam	1
10	0
mg	0
and	0
atropine	1
0	0
.	0
5	0
mg	0
was	0
given	0
,	0
and	0
sleep	0
was	0
induced	0
and	0
maintained	0
by	0
intermittent	0
intravenous	0
injections	0
of	0
etomidate	1
0	0
.	0
1	0
/	0
mg	0
/	0
kg	0
,	0
given	0
whenever	0
the	0
patient	0
would	0
open	0
his	0
eyes	0
on	0
request	0
.	0

A	0
mean	0
overall	0
dose	0
of	0
etomidate	1
17	0
.	0
4	0
microgram	0
/	0
kg	0
/	0
min	0
.	0
was	0
required	0
to	0
maintain	0
sleep	0
,	0
but	0
great	0
individual	0
variation	0
occurred	0
,	0
with	0
older	0
patients	0
requiring	0
less	0
drug	0
.	0

The	0
investigation	0
was	0
discontinued	0
after	0
18	0
patients	0
because	0
of	0
the	0
frequency	0
and	0
intensity	0
of	0
side	0
-	0
effects	0
,	0
particularly	0
pain	3
and	0
myoclonia	3
,	0
which	0
caused	0
the	0
technique	0
to	0
be	0
abandoned	0
in	0
two	0
cases	0
.	0

It	0
is	0
considered	0
unlikely	0
that	0
etomidate	1
will	0
prove	0
to	0
be	0
the	0
hypnotic	0
of	0
choice	0
for	0
a	0
totally	0
intravenous	0
anesthetic	0
technique	0
in	0
adults	0
because	0
of	0
the	0
high	0
incidence	0
of	0
myoclonia	3
after	0
prolonged	0
administration	0
.	0

In	0
several	0
patients	0
uncontrollable	0
muscle	0
movements	0
persisted	0
for	0
many	0
minutes	0
after	0
complete	0
recovery	0
of	0
consciousness	0
.	0

Evidence	0
for	0
cardiac	0
beta	0
2	0
-	0
adrenoceptors	0
in	0
man	0
.	0

We	0
compared	0
the	0
effects	0
of	0
single	0
doses	0
of	0
50	0
mg	0
atenolol	1
(	0
cardioselective	0
)	0
,	0
40	0
mg	0
propranolol	1
(	0
nonselective	0
)	0
,	0
and	0
placebo	0
on	0
both	0
exercise	0
-	0
and	0
isoproterenol	1
-	0
induced	0
tachycardia	3
in	0
two	0
experiments	0
involving	0
nine	0
normal	0
subjects	0
.	0

Maximal	0
exercise	0
heart	0
rate	0
was	0
reduced	0
from	0
187	0
+	0
/	0
-	0
4	0
(	0
SEM	0
)	0
after	0
placebo	0
to	0
146	0
+	0
/	0
-	0
7	0
bpm	0
after	0
atenolol	1
and	0
138	0
+	0
/	0
-	0
6	0
bpm	0
after	0
propranolol	1
,	0
but	0
there	0
were	0
no	0
differences	0
between	0
the	0
drugs	0
.	0

The	0
effects	0
on	0
isoproterenol	1
tachycardia	3
were	0
determined	0
before	0
and	0
after	0
atropine	1
(	0
0	0
.	0
04	0
mg	0
/	0
kg	0
IV	0
)	0
.	0

Isoproterenol	1
sensitivity	0
was	0
determined	0
as	0
the	0
intravenous	0
dose	0
that	0
increased	0
heart	0
rate	0
by	0
25	0
bpm	0
(	0
CD25	0
)	0
and	0
this	0
was	0
increased	0
from	0
1	0
.	0
8	0
+	0
/	0
-	0
0	0
.	0
3	0
micrograms	0
after	0
placebo	0
to	0
38	0
.	0
9	0
+	0
/	0
-	0
8	0
.	0
3	0
micrograms	0
after	0
propranolol	1
and	0
8	0
.	0
3	0
+	0
/	0
-	0
1	0
.	0
7	0
micrograms	0
after	0
atenolol	1
.	0

The	0
difference	0
in	0
the	0
effects	0
of	0
the	0
two	0
was	0
significant	0
.	0

After	0
atropine	1
the	0
CD25	0
was	0
unchanged	0
after	0
placebo	0
(	0
2	0
.	0
3	0
+	0
/	0
-	0
0	0
.	0
3	0
micrograms	0
)	0
and	0
atenolol	1
(	0
7	0
.	0
7	0
+	0
/	0
-	0
1	0
.	0
3	0
micrograms	0
)	0
;	0
it	0
was	0
reduced	0
after	0
propranolol	1
(	0
24	0
.	0
8	0
+	0
/	0
-	0
5	0
.	0
0	0
micrograms	0
)	0
,	0
but	0
remained	0
different	0
from	0
atenolol	1
.	0

This	0
change	0
with	0
propranolol	1
sensitivity	0
was	0
calculated	0
as	0
the	0
apparent	0
Ka	0
,	0
this	0
was	0
unchanged	0
by	0
atropine	1
(	0
11	0
.	0
7	0
+	0
/	0
-	0
2	0
.	0
1	0
and	0
10	0
.	0
1	0
+	0
/	0
-	0
2	0
.	0
5	0
ml	0
/	0
ng	0
)	0
.	0

These	0
data	0
are	0
consistent	0
with	0
the	0
hypothesis	0
that	0
exercise	0
-	0
induced	0
tachycardia	3
results	0
largely	0
from	0
beta	0
1	0
-	0
receptor	0
activation	0
that	0
is	0
blocked	0
by	0
both	0
cardioselective	0
and	0
nonselective	0
drugs	0
,	0
whereas	0
isoproterenol	1
activates	0
both	0
beta	0
1	0
-	0
and	0
beta	0
2	0
-	0
receptors	0
so	0
that	0
after	0
cardioselective	0
blockade	0
there	0
remains	0
a	0
beta	0
2	0
-	0
component	0
that	0
can	0
be	0
blocked	0
with	0
a	0
nonselective	0
drug	0
.	0

While	0
there	0
appear	0
to	0
be	0
beta	0
2	0
-	0
receptors	0
in	0
the	0
human	0
heart	0
,	0
their	0
physiologic	0
or	0
pathologic	0
roles	0
remain	0
to	0
be	0
defined	0
.	0

Hormones	0
and	0
risk	0
of	0
breast	3
cancer	4
.	0

This	0
paper	0
reports	0
the	0
results	0
of	0
a	0
study	0
of	0
50	0
menopausal	0
women	0
receiving	0
hormonal	0
replacement	0
therapy	0
.	0

The	0
majority	0
(	0
29	0
)	0
had	0
surgical	0
menopause	0
;	0
their	0
mean	0
age	0
was	0
45	0
.	0
7	0
years	0
.	0

It	0
was	0
hypothesized	0
that	0
progestins	1
could	0
equilibrate	0
the	0
effects	0
of	0
the	0
estrogenic	0
stimulation	0
on	0
the	0
mammary	0
and	0
endometrial	0
target	0
tissues	0
of	0
women	0
on	0
hormonal	0
replacement	0
therapy	0
.	0

The	0
treatment	0
schedule	0
consisted	0
of	0
conjugated	1
estrogens	2
(	0
Premarin	1
)	0
1	0
.	0
25	0
mg	0
/	0
day	0
for	0
21	0
days	0
and	0
Medroxyprogesterone	1
acetate	2
10	0
mg	0
/	0
day	0
for	0
10	0
days	0
in	0
each	0
month	0
.	0

The	0
mean	0
treatment	0
period	0
was	0
18	0
months	0
.	0

During	0
the	0
follow	0
-	0
up	0
period	0
,	0
attention	0
was	0
paid	0
to	0
breast	0
modifications	0
as	0
evidenced	0
by	0
symptomatology	0
,	0
physical	0
examination	0
,	0
and	0
plate	0
thermography	0
.	0

Mastodynia	3
was	0
reported	0
by	0
21	0
patients	0
,	0
and	0
physical	0
examination	0
revealed	0
a	0
light	0
increase	0
in	0
breast	0
firmness	0
in	0
12	0
women	0
and	0
a	0
moderate	0
increase	0
in	0
breast	0
nodularity	0
in	0
2	0
women	0
.	0

Themography	0
confirmed	0
the	0
existence	0
of	0
an	0
excessive	0
breast	0
stimulation	0
in	0
1	0
women	0
who	0
complained	0
of	0
moderate	0
mastodynia	3
and	0
in	0
5	0
of	0
the	0
7	0
women	0
who	0
complained	0
of	0
severe	0
mastodynia	3
.	0

Normalization	0
was	0
obtained	0
by	0
halving	0
the	0
estrogen	1
dose	0
.	0

These	0
results	0
suggest	0
that	0
hormonal	0
replacement	0
therapy	0
can	0
be	0
safely	0
prescribed	0
if	0
the	0
following	0
criteria	0
are	0
satisfied	0
:	0
1	0
)	0
preliminary	0
evaluation	0
of	0
patients	0
from	0
a	0
clinical	0
,	0
metabolic	0
,	0
cytologic	0
,	0
and	0
mammographic	0
perspective	0
;	0
2	0
)	0
cyclic	0
treatment	0
schedule	0
,	0
with	0
a	0
progestative	0
phase	0
of	0
10	0
days	0
;	0
and	0
3	0
)	0
periodic	0
complete	0
follow	0
-	0
up	0
,	0
with	0
accurate	0
thermographic	0
evaluation	0
of	0
the	0
breast	0
target	0
tissues	0
.	0

Early	0
infections	3
in	0
kidney	0
,	0
heart	0
,	0
and	0
liver	0
transplant	0
recipients	0
on	0
cyclosporine	1
.	0

Eighty	0
-	0
one	0
renal	0
,	0
seventeen	0
heart	0
,	0
and	0
twenty	0
-	0
four	0
liver	0
transplant	0
patients	0
were	0
followed	0
for	0
infection	3
.	0

Seventeen	0
renal	0
patients	0
received	0
azathioprine	1
(	0
Aza	1
)	0
and	0
prednisone	1
as	0
part	0
of	0
a	0
randomized	0
trial	0
of	0
immunosuppression	0
with	0
21	0
cyclosporine	1
-	0
and	0
-	0
prednisone	1
-	0
treated	0
renal	0
transplant	0
patients	0
.	0

All	0
others	0
received	0
cyclosporine	1
and	0
prednisone	1
.	0

The	0
randomized	0
Aza	1
patients	0
had	0
more	0
overall	0
infections	3
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
and	0
more	0
nonviral	0
infections	3
(	0
P	0
less	0
than	0
0	0
.	0
02	0
)	0
than	0
the	0
randomized	0
cyclosporine	1
patients	0
.	0

Heart	0
and	0
liver	0
patients	0
had	0
more	0
infections	3
than	0
cyclosporine	1
renal	0
patients	0
but	0
fewer	0
infections	3
than	0
the	0
Aza	1
renal	0
patients	0
.	0

There	0
were	0
no	0
infectious	0
deaths	0
in	0
renal	0
transplant	0
patients	0
on	0
cyclosporine	1
or	0
Aza	1
,	0
but	0
infection	3
played	0
a	0
major	0
role	0
in	0
3	0
out	0
of	0
6	0
cardiac	0
transplant	0
deaths	0
and	0
in	0
8	0
out	0
of	0
9	0
liver	0
transplant	0
deaths	0
.	0

Renal	0
patients	0
on	0
cyclosporine	1
had	0
the	0
fewest	0
bacteremias	3
.	0

Analysis	0
of	0
site	0
of	0
infection	3
showed	0
a	0
preponderance	0
of	0
abdominal	3
infections	4
in	0
liver	0
patients	0
,	0
intrathoracic	0
infections	3
in	0
heart	0
patients	0
,	0
and	0
urinary	3
tract	4
infections	4
in	0
renal	0
patients	0
.	0

Pulmonary	0
infections	3
were	0
less	0
common	0
in	0
cyclosporine	1
-	0
treated	0
renal	0
patients	0
than	0
in	0
Aza	1
-	0
treated	0
patients	0
(	0
P	0
less	0
than	0
0	0
.	0
05	0
)	0
.	0

Aza	1
patients	0
had	0
significantly	0
more	0
staphylococcal	3
infections	4
than	0
all	0
other	0
transplant	0
groups	0
(	0
P	0
less	0
than	0
0	0
.	0
005	0
)	0
,	0
and	0
systemic	0
fungal	3
infections	4
occurred	0
only	0
in	0
the	0
liver	0
transplant	0
group	0
.	0

Cytomegalovirus	0
(	0
CMV	0
)	0
shedding	0
or	0
serological	0
rises	0
in	0
antibody	0
titer	0
,	0
or	0
both	0
occurred	0
in	0
78	0
%	0
of	0
cyclosporine	1
patients	0
and	0
76	0
%	0
of	0
Aza	1
patients	0
.	0

0f	0
the	0
cyclosporine	1
patients	0
,	0
15	0
%	0
had	0
symptoms	0
related	0
to	0
CMV	3
infection	4
.	0

Serological	0
evidence	0
for	0
Epstein	3
Barr	4
Virus	4
infection	4
was	0
found	0
in	0
20	0
%	0
of	0
65	0
cyclosporine	1
patients	0
studied	0
.	0

Three	0
had	0
associated	0
symptoms	0
,	0
and	0
one	0
developed	0
a	0
lymphoma	3
.	0

Structure	0
-	0
activity	0
and	0
dose	0
-	0
effect	0
relationships	0
of	0
the	0
antagonism	0
of	0
picrotoxin	1
-	0
induced	0
seizures	3
by	0
cholecystokinin	1
,	0
fragments	0
and	0
analogues	0
of	0
cholecystokinin	1
in	0
mice	0
.	0

Intraperitoneal	0
administration	0
of	0
cholecystokinin	1
octapeptide	2
sulphate	0
ester	0
(	0
CCK	1
-	2
8	2
-	0
SE	0
)	0
and	0
nonsulphated	0
cholecystokinin	1
octapeptide	2
(	0
CCK	1
-	2
8	2
-	0
NS	0
)	0
enhanced	0
the	0
latency	0
of	0
seizures	3
induced	0
by	0
picrotoxin	1
in	0
mice	0
.	0

Experiments	0
with	0
N	0
-	0
and	0
C	0
-	0
terminal	0
fragments	0
revealed	0
that	0
the	0
C	0
-	0
terminal	0
tetrapeptide	0
(	0
CCK	0
-	0
5	0
-	0
8	0
)	0
was	0
the	0
active	0
centre	0
of	0
the	0
CCK	0
octapeptide	0
molecule	0
.	0

The	0
analogues	0
CCK	1
-	2
8	2
-	0
SE	0
and	0
CCK	1
-	2
8	2
-	0
NS	0
(	0
dose	0
range	0
0	0
.	0
2	0
-	0
6	0
.	0
4	0
mumol	0
/	0
kg	0
)	0
and	0
caerulein	1
dose	0
range	0
0	0
.	0
1	0
-	0
0	0
.	0
8	0
mumol	0
/	0
kg	0
)	0
showed	0
bell	0
-	0
shaped	0
dose	0
-	0
effect	0
curves	0
,	0
with	0
the	0
greatest	0
maximum	0
inhibition	0
for	0
CCK	1
-	2
8	2
-	0
NS	0
.	0

The	0
peptide	0
CCK	0
-	0
5	0
-	0
8	0
had	0
weak	0
anticonvulsant	0
activity	0
in	0
comparison	0
to	0
the	0
octapeptides	0
,	0
3	0
.	0
2	0
mumol	0
/	0
kg	0
and	0
larger	0
doses	0
of	0
the	0
reference	0
drug	0
,	0
diazepam	1
,	0
totally	0
prevented	0
picrotoxin	1
-	0
induced	0
seizures	3
and	0
mortality	0
.	0

The	0
maximum	0
effect	0
of	0
the	0
peptides	0
tested	0
was	0
less	0
than	0
that	0
of	0
diazepam	1
.	0

Experiments	0
with	0
analogues	0
and	0
derivatives	0
of	0
CCK	0
-	0
5	0
-	0
8	0
demonstrated	0
that	0
the	0
effectiveness	0
of	0
the	0
beta	0
-	0
alanyl	0
derivatives	0
of	0
CCK	0
-	0
5	0
-	0
8	0
were	0
enhanced	0
and	0
that	0
they	0
were	0
equipotent	0
with	0
CCK	1
-	2
8	2
-	0
SE	0
.	0

0f	0
the	0
CCK	0
-	0
2	0
-	0
8	0
analogues	0
,	0
Ser	0
(	0
S03H	0
)	0
7	0
-	0
Ac	0
-	0
CCK	0
-	0
2	0
-	0
8	0
-	0
SE	0
and	0
Thr	0
(	0
S03H	0
)	0
7	0
-	0
Ac	0
-	0
CCK	0
-	0
2	0
-	0
8	0
-	0
SE	0
and	0
Hyp	0
(	0
S03H	0
)	0
-	0
Ac	0
-	0
CCK	0
-	0
2	0
-	0
8	0
-	0
SE	0
were	0
slightly	0
more	0
active	0
than	0
CCK	1
-	2
8	2
-	0
SE	0
.	0

Vasopressin	1
as	0
a	0
possible	0
contributor	0
to	0
hypertension	3
.	0

The	0
role	0
of	0
vasopressin	1
as	0
a	0
pressor	0
agent	0
to	0
the	0
hypertensive	3
process	0
was	0
examined	0
.	0

Vasopressin	1
plays	0
a	0
major	0
role	0
in	0
the	0
pathogenesis	0
of	0
D0CA	1
-	0
salt	0
hypertension	3
,	0
since	0
the	0
elevation	0
of	0
blood	0
pressure	0
was	0
not	0
substantial	0
in	0
the	0
rats	0
with	0
lithium	1
-	0
treated	0
diabetes	3
insipidus	4
after	0
D0CA	1
-	0
salt	0
treatment	0
.	0

Administration	0
of	0
DDAVP	1
which	0
has	0
antidiuretic	0
action	0
but	0
minimal	0
vasopressor	0
effect	0
failed	0
to	0
increase	0
blood	0
pressure	0
to	0
the	0
levels	0
observed	0
after	0
administration	0
of	0
AVP	0
.	0

Furthermore	0
,	0
the	0
pressor	0
action	0
of	0
vasopressin	1
appears	0
to	0
be	0
important	0
in	0
the	0
development	0
of	0
this	0
model	0
of	0
hypertension	3
,	0
since	0
the	0
enhanced	0
pressor	0
responsiveness	0
to	0
the	0
hormone	0
was	0
observed	0
in	0
the	0
initial	0
stage	0
of	0
hypertension	3
.	0

Increased	0
secretion	0
of	0
vasopressin	1
from	0
neurohypophysis	0
also	0
promotes	0
the	0
function	0
of	0
the	0
hormone	0
as	0
a	0
pathogenetic	0
factor	0
in	0
hypertension	3
.	0

An	0
unproportional	0
release	0
of	0
vasopressin	1
compared	0
to	0
plasma	0
osmolality	0
may	0
be	0
induced	0
by	0
the	0
absence	0
of	0
an	0
adjusting	0
control	0
of	0
angiotensin	1
II	0
forming	0
and	0
receptor	0
binding	0
capacity	0
for	0
sodium	1
balance	0
in	0
the	0
brain	0
.	0

However	0
,	0
the	0
role	0
of	0
vasopressin	1
remains	0
to	0
be	0
determined	0
in	0
human	0
essential	0
hypertension	3
.	0

Toxic	3
hepatitis	4
induced	0
by	0
disulfiram	1
in	0
a	0
non	0
-	0
alcoholic	0
.	0

A	0
reversible	0
toxic	3
liver	4
damage	4
was	0
observed	0
in	0
a	0
non	0
-	0
alcoholic	0
woman	0
treated	0
with	0
disulfiram	1
.	0

The	0
causative	0
relationship	0
was	0
proven	0
by	0
challenge	0
.	0

Atrial	3
thrombosis	4
involving	0
the	0
heart	0
of	0
F	0
-	0
344	0
rats	0
ingesting	0
quinacrine	1
hydrochloride	2
.	0

Quinacrine	1
hydrochloride	2
is	0
toxic	0
for	0
the	0
heart	0
of	0
F	0
-	0
344	0
rats	0
.	0

Rats	0
treated	0
with	0
500	0
ppm	0
quinacrine	1
hydrochloride	2
in	0
the	0
diet	0
all	0
developed	0
a	0
high	0
incidence	0
of	0
left	0
atrial	3
thrombosis	4
.	0

The	0
lesion	0
was	0
associated	0
with	0
cardiac	3
hypertrophy	4
and	0
dilatation	0
and	0
focal	0
myocardial	3
degeneration	4
.	0

Rats	0
died	0
from	0
cardiac	3
hypertrophy	4
with	0
severe	0
acute	0
and	0
chronic	0
congestion	0
of	0
the	0
lungs	0
,	0
liver	0
,	0
and	0
other	0
organs	0
.	0

Seventy	0
percent	0
of	0
rats	0
given	0
250	0
ppm	0
quinacrine	1
hydrochloride	2
and	0
1	0
,	0
000	0
ppm	0
sodium	1
nitrite	2
simultaneously	0
in	0
the	0
diet	0
had	0
thrombosis	3
of	0
the	0
atria	0
of	0
the	0
heart	0
,	0
while	0
untreated	0
control	0
rats	0
in	0
this	0
laboratory	0
did	0
not	0
have	0
atrial	3
thrombosis	4
.	0

Sodium	1
nitrite	2
in	0
combination	0
with	0
quinacrine	1
hydrochloride	2
appeared	0
to	0
have	0
no	0
additional	0
effect	0
.	0

Alternating	3
sinus	4
rhythm	4
and	0
intermittent	0
sinoatrial	3
block	4
induced	0
by	0
propranolol	1
.	0

Alternating	3
sinus	4
rhythm	4
and	0
intermittent	0
sinoatrial	3
(	4
S	4
-	4
A	4
)	4
block	4
was	0
observed	0
in	0
a	0
57	0
-	0
year	0
-	0
old	0
woman	0
,	0
under	0
treatment	0
for	0
angina	3
with	0
80	0
mg	0
propranolol	1
daily	0
.	0

The	0
electrocardiogram	0
showed	0
alternation	0
of	0
long	0
and	0
short	0
P	0
-	0
P	0
intervals	0
and	0
occasional	0
pauses	0
.	0

These	0
pauses	0
were	0
always	0
preceded	0
by	0
the	0
short	0
P	0
-	0
P	0
intervals	0
and	0
were	0
usually	0
followed	0
by	0
one	0
or	0
two	0
P	0
-	0
P	0
intervals	0
of	0
0	0
.	0
92	0
-	0
0	0
.	0
95	0
s	0
representing	0
the	0
basic	0
sinus	0
cycle	0
.	0

Following	0
these	0
basic	0
sinus	0
cycles	0
,	0
alternating	3
rhythm	4
started	0
with	0
the	0
longer	0
P	0
-	0
P	0
interval	0
.	0

The	0
long	0
P	0
-	0
P	0
intervals	0
ranged	0
between	0
1	0
.	0
04	0
-	0
1	0
.	0
12	0
s	0
and	0
the	0
short	0
P	0
-	0
P	0
intervals	0
between	0
0	0
.	0
80	0
-	0
0	0
.	0
84	0
s	0
,	0
respectively	0
.	0

The	0
duration	0
of	0
the	0
pauses	0
were	0
equal	0
or	0
almost	0
equal	0
to	0
one	0
short	0
plus	0
one	0
long	0
P	0
-	0
P	0
interval	0
or	0
to	0
twice	0
the	0
basic	0
sinus	0
cycle	0
.	0

In	0
one	0
recording	0
a	0
short	0
period	0
of	0
regular	0
sinus	0
rhythm	0
with	0
intermittent	0
2	0
/	0
1	0
S	3
-	4
A	4
block	4
was	0
observed	0
.	0

This	0
short	0
period	0
of	0
sinus	0
rhythm	0
was	0
interrupted	0
by	0
sudden	0
prolongation	0
of	0
the	0
P	0
-	0
P	0
interval	0
starting	0
the	0
alternative	0
rhythm	0
.	0

There	0
were	0
small	0
changes	0
in	0
the	0
shape	0
of	0
the	0
P	0
waves	0
and	0
P	0
-	0
R	0
intervals	0
.	0

S	0
-	0
A	0
conduction	0
through	0
two	0
pathways	0
,	0
the	0
first	0
with	0
2	0
/	0
1	0
block	0
the	0
second	0
having	0
0	0
.	0
12	0
-	0
0	0
.	0
14	0
s	0
longer	0
conduction	0
time	0
and	0
with	0
occasional	0
2	0
/	0
1	0
block	0
was	0
proposed	0
for	0
the	0
explanation	0
of	0
the	0
alternating	0
P	0
-	0
P	0
interval	0
and	0
other	0
electrocardiographic	0
features	0
seen	0
.	0

Atropine	1
1	0
mg	0
given	0
intravenously	0
resulted	0
in	0
shortening	0
of	0
all	0
P	0
-	0
P	0
intervals	0
without	0
changing	0
the	0
rhythm	0
.	0

The	0
abnormal	0
rhythm	0
disappeared	0
with	0
the	0
withdrawal	0
of	0
propranolol	1
and	0
when	0
the	0
drug	0
was	0
restarted	0
a	0
2	0
/	0
1	0
S	3
-	4
A	4
block	4
was	0
seen	0
.	0

This	0
was	0
accepted	0
as	0
evidence	0
for	0
propranolol	1
being	0
the	0
cause	0
of	0
this	0
conduction	3
disorder	4
.	0

Antitumor	0
effect	0
,	0
cardiotoxicity	3
,	0
and	0
nephrotoxicity	3
of	0
doxorubicin	1
in	0
the	0
IgM	0
solid	0
immunocytoma	3
-	0
bearing	0
L0U	0
/	0
M	0
/	0
WSL	0
rat	0
.	0

Antitumor	0
activity	0
,	0
cardiotoxicity	3
,	0
and	0
nephrotoxicity	3
induced	0
by	0
doxorubicin	1
were	0
studied	0
in	0
L0U	0
/	0
M	0
/	0
WSL	0
inbred	0
rats	0
each	0
bearing	0
a	0
transplantable	0
solid	0
IgM	0
immunocytoma	3
.	0

Animals	0
with	0
a	0
tumor	3
(	0
diameter	0
,	0
15	0
.	0
8	0
+	0
/	0
-	0
3	0
.	0
3	0
mm	0
)	0
were	0
treated	0
with	0
iv	0
injections	0
of	0
doxorubicin	1
on	0
5	0
consecutive	0
days	0
,	0
followed	0
by	0
1	0
weekly	0
injection	0
for	0
7	0
weeks	0
(	0
dose	0
range	0
,	0
0	0
.	0
015	0
-	0
4	0
.	0
0	0
mg	0
/	0
kg	0
body	0
wt	0
)	0
.	0

Tumor	3
regression	0
was	0
observed	0
with	0
0	0
.	0
5	0
mg	0
doxorubicin	1
/	0
kg	0
.	0

Complete	0
disappearance	0
of	0
the	0
tumor	3
was	0
induced	0
with	0
1	0
.	0
0	0
mg	0
doxorubicin	1
/	0
kg	0
.	0

Histologic	0
evidence	0
of	0
cardiotoxicity	3
scored	0
as	0
grade	0
III	0
was	0
only	0
observed	0
at	0
a	0
dose	0
of	0
1	0
.	0
0	0
mg	0
doxorubicin	1
/	0
kg	0
.	0

Light	0
microscopic	0
evidence	0
of	0
renal	3
damage	4
was	0
seen	0
above	0
a	0
dose	0
of	0
0	0
.	0
5	0
mg	0
doxorubicin	1
/	0
kg	0
,	0
which	0
resulted	0
in	0
albuminuria	3
and	0
very	0
low	0
serum	0
albumin	0
levels	0
.	0

In	0
the	0
group	0
that	0
received	0
1	0
.	0
0	0
mg	0
doxorubicin	1
/	0
kg	0
,	0
the	0
serum	0
albumin	0
level	0
decreased	0
from	0
33	0
.	0
6	0
+	0
/	0
-	0
4	0
.	0
1	0
to	0
1	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
5	0
g	0
/	0
liter	0
.	0

Ascites	3
and	0
hydrothorax	3
were	0
observed	0
simultaneously	0
.	0

The	0
same	0
experiments	0
were	0
performed	0
with	0
non	0
-	0
tumor	3
-	0
bearing	0
rats	0
,	0
in	0
which	0
no	0
major	0
differences	0
were	0
observed	0
.	0

In	0
conclusion	0
,	0
antitumor	0
activity	0
,	0
cardiotoxicity	3
,	0
and	0
nephrotoxicity	3
were	0
studied	0
simultaneously	0
in	0
the	0
same	0
L0U	0
/	0
M	0
/	0
WSL	0
rat	0
.	0

Albuminuria	3
due	0
to	0
renal	3
damage	4
led	0
to	0
extremely	0
low	0
serum	0
albumin	0
levels	0
,	0
so	0
ascites	3
and	0
hydrothorax	3
were	0
not	0
necessarily	0
a	0
consequence	0
of	0
the	0
observed	0
cardiomyopathy	3
.	0

Intraoperative	0
bradycardia	3
and	0
hypotension	3
associated	0
with	0
timolol	1
and	0
pilocarpine	1
eye	0
drops	0
.	0

A	0
69	0
-	0
yr	0
-	0
old	0
man	0
,	0
who	0
was	0
concurrently	0
being	0
treated	0
with	0
pilocarpine	1
nitrate	2
and	0
timolol	1
maleate	2
eye	0
drops	0
,	0
developed	0
a	0
bradycardia	3
and	0
became	0
hypotensive	3
during	0
halothane	1
anaesthesia	0
.	0

Both	0
timolol	1
and	0
pilocarpine	1
were	0
subsequently	0
identified	0
in	0
a	0
24	0
-	0
h	0
collection	0
of	0
urine	0
.	0

Timolol	1
(	0
but	0
not	0
pilocarpine	1
)	0
was	0
detected	0
in	0
a	0
sample	0
of	0
plasma	0
removed	0
during	0
surgery	0
;	0
the	0
plasma	0
concentration	0
of	0
timolol	1
(	0
2	0
.	0
6	0
ng	0
ml	0
-	0
1	0
)	0
was	0
consistent	0
with	0
partial	0
beta	0
-	0
adrenoceptor	0
blockade	0
.	0

It	0
is	0
postulated	0
that	0
this	0
action	0
may	0
have	0
been	0
enhanced	0
during	0
halothane	1
anaesthesia	0
with	0
resultant	0
bradycardia	3
and	0
hypotension	3
.	0

Pilocarpine	1
may	0
have	0
had	0
a	0
contributory	0
effect	0
.	0

Succinylcholine	1
apnoea	3
:	0
attempted	0
reversal	0
with	0
anticholinesterases	0
.	0

Anticholinesterases	0
were	0
administered	0
in	0
an	0
attempt	0
to	0
antagonize	0
prolonged	0
neuromuscular	3
blockade	4
following	0
the	0
administration	0
of	0
succinylcholine	1
in	0
a	0
patient	0
later	0
found	0
to	0
be	0
homozygous	0
for	0
atypical	0
plasma	0
cholinesterase	0
.	0

Edrophonium	1
10	0
mg	0
,	0
given	0
74	0
min	0
after	0
succinylcholine	1
,	0
when	0
train	0
-	0
of	0
-	0
four	0
stimulation	0
was	0
characteristic	0
of	0
phase	0
II	0
block	0
,	0
produced	0
partial	0
antagonism	0
which	0
was	0
not	0
sustained	0
.	0

Repeated	0
doses	0
of	0
edrophonium	1
to	0
70	0
mg	0
and	0
neostigmine	1
to	0
2	0
.	0
5	0
mg	0
did	0
not	0
antagonize	0
or	0
augment	0
the	0
block	0
.	0

Spontaneous	0
respiration	0
recommenced	0
200	0
min	0
after	0
succinylcholine	1
administration	0
.	0

It	0
is	0
concluded	0
that	0
anticholinesterases	0
are	0
only	0
partially	0
effective	0
in	0
restoring	0
neuromuscular	0
function	0
in	0
succinylcholine	1
apnoea	3
despite	0
muscle	0
twitch	0
activity	0
typical	0
of	0
phase	0
II	0
block	0
.	0

Effect	0
of	0
doxorubicin	1
on	0
[	1
omega	2
-	2
I	2
-	2
131	2
]	2
heptadecanoic	2
acid	2
myocardial	0
scintigraphy	0
and	0
echocardiography	0
in	0
dogs	0
.	0

The	0
effects	0
of	0
serial	0
treatment	0
with	0
doxorubicin	1
on	0
dynamic	0
myocardial	0
scintigraphy	0
with	0
[	1
omega	2
-	2
I	2
-	2
131	2
]	2
heptadecanoic	2
acid	2
(	0
I	1
-	2
131	2
HA	2
)	0
,	0
and	0
on	0
global	0
left	0
-	0
ventricular	0
function	0
determined	0
echocardiographically	0
,	0
were	0
studied	0
in	0
a	0
group	0
of	0
nine	0
mongrel	0
dogs	0
.	0

Total	0
extractable	0
myocardial	0
lipid	0
was	0
compared	0
postmortem	0
between	0
a	0
group	0
of	0
control	0
dogs	0
and	0
doxorubicin	1
-	0
treated	0
dogs	0
.	0

A	0
significant	0
and	0
then	0
progressive	0
fall	0
in	0
global	0
LV	0
function	0
was	0
observed	0
at	0
a	0
cumulative	0
doxorubicin	1
dose	0
of	0
4	0
mg	0
/	0
kg	0
.	0

A	0
significant	0
increase	0
in	0
the	0
myocardial	0
t1	0
/	0
2	0
of	0
the	0
I	1
-	2
131	2
HA	2
was	0
observed	0
only	0
at	0
a	0
higher	0
cumulative	0
dose	0
,	0
10	0
mg	0
/	0
kg	0
.	0

No	0
significant	0
alteration	0
in	0
total	0
extractable	0
myocardial	0
lipids	0
was	0
observed	0
between	0
control	0
dogs	0
and	0
those	0
treated	0
with	0
doxorubicin	1
.	0

0ur	0
findings	0
suggest	0
that	0
the	0
changes	0
leading	0
to	0
an	0
alteration	0
of	0
myocardial	0
dynamic	0
imaging	0
with	0
I	1
-	2
131	2
HA	2
are	0
not	0
the	0
initiating	0
factor	0
in	0
doxorubicin	1
cardiotoxicity	3
.	0

Hemodynamics	0
and	0
myocardial	0
metabolism	0
under	0
deliberate	0
hypotension	3
.	0

An	0
experimental	0
study	0
in	0
dogs	0
.	0

Coronary	0
blood	0
flow	0
,	0
cardiac	0
work	0
and	0
metabolism	0
were	0
studied	0
in	0
dogs	0
under	0
sodium	1
nitroprusside	2
(	0
SNP	1
)	0
and	0
trimetaphan	1
(	0
TMP	1
)	0
deliberate	0
hypotension	3
(	0
20	0
%	0
and	0
40	0
%	0
mean	0
pressure	0
decrease	0
from	0
baseline	0
)	0
.	0

Regarding	0
the	0
effects	0
of	0
drug	0
-	0
induced	0
hypotension	3
on	0
coronary	0
blood	0
flow	0
,	0
aortic	0
and	0
coronary	0
sinus	0
metabolic	0
data	0
(	0
pH	0
,	0
p02	0
,	0
pC02	0
)	0
we	0
could	0
confirm	0
that	0
nitroprusside	1
hypotension	3
could	0
be	0
safely	0
used	0
to	0
30	0
%	0
mean	0
blood	0
pressure	0
decrease	0
from	0
control	0
,	0
trimetaphan	1
hypotension	3
to	0
20	0
%	0
mean	0
blood	0
pressure	0
decrease	0
.	0

Cardiac	0
work	0
was	0
significantly	0
reduced	0
during	0
SNP	1
hypotension	3
.	0

Myocardial	0
02	1
consumption	0
and	0
02	1
availability	0
were	0
directly	0
dependent	0
on	0
the	0
coronary	0
perfusion	0
.	0

Careful	0
invasive	0
monitoring	0
of	0
the	0
blood	0
pressure	0
,	0
blood	0
gases	0
and	0
of	0
the	0
ECG	0
ST	0
-	0
T	0
segment	0
is	0
mandatory	0
.	0

Evidence	0
for	0
a	0
selective	0
brain	0
noradrenergic	0
involvement	0
in	0
the	0
locomotor	0
stimulant	0
effects	0
of	0
amphetamine	1
in	0
the	0
rat	0
.	0

Male	0
rats	0
received	0
the	0
noradrenaline	1
neurotoxin	0
DSP4	1
(	0
50	0
mg	0
/	0
kg	0
)	0
7	0
days	0
prior	0
to	0
injection	0
of	0
D	1
-	2
amphetamine	2
(	0
10	0
or	0
40	0
mumol	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
.	0

The	0
hyperactivity	3
induced	0
by	0
D	1
-	2
amphetamine	2
(	0
10	0
mumol	0
/	0
kg	0
)	0
was	0
significantly	0
reduced	0
by	0
DSP4	1
pretreatment	0
.	0

However	0
,	0
the	0
increased	0
rearings	0
and	0
the	0
amphetamine	1
-	0
induced	0
stereotypies	3
were	0
not	0
blocked	0
by	0
pretreatment	0
with	0
DSP4	1
.	0

The	0
reduction	0
of	0
amphetamine	1
hyperactivity	3
induced	0
by	0
DSP4	1
was	0
blocked	0
by	0
pretreatment	0
with	0
the	0
noradrenaline	1
-	0
uptake	0
blocking	0
agent	0
,	0
desipramine	1
,	0
which	0
prevents	0
the	0
neurotoxic	3
action	0
of	0
DSP4	1
.	0

The	0
present	0
results	0
suggest	0
a	0
selective	0
involvement	0
of	0
central	0
noradrenergic	0
neurones	0
in	0
the	0
locomotor	0
stimulant	0
effect	0
of	0
amphetamine	1
in	0
the	0
rat	0
.	0

Accelerated	3
junctional	4
rhythms	4
during	0
oral	0
verapamil	1
therapy	0
.	0

This	0
study	0
examined	0
the	0
frequency	0
of	0
atrioventricular	0
(	0
AV	0
)	0
dissociation	0
and	0
accelerated	3
junctional	4
rhythms	4
in	0
59	0
patients	0
receiving	0
oral	0
verapamil	1
.	0

Accelerated	3
junctional	4
rhythms	4
and	0
AV	0
dissociation	0
were	0
frequent	0
in	0
patients	0
with	0
supraventricular	3
tachyarrhythmias	4
,	0
particularly	0
AV	0
nodal	0
reentry	0
.	0

Verapamil	1
administration	0
to	0
these	0
patients	0
led	0
to	0
an	0
asymptomatic	0
increase	0
in	0
activity	0
of	0
these	0
junctional	0
pacemakers	0
.	0

In	0
patients	0
with	0
various	0
chest	3
pain	4
syndromes	0
,	0
verapamil	1
neither	0
increased	0
the	0
frequency	0
of	0
junctional	0
rhythms	0
nor	0
suppressed	0
their	0
role	0
as	0
escape	0
rhythms	0
under	0
physiologically	0
appropriate	0
circumstances	0
.	0

Interstrain	0
variation	0
in	0
acute	0
toxic	0
response	0
to	0
caffeine	1
among	0
inbred	0
mice	0
.	0

Acute	0
toxic	0
dosage	0
-	0
dependent	0
behavioral	0
effects	0
of	0
caffeine	1
were	0
compared	0
in	0
adult	0
males	0
from	0
seven	0
inbred	0
mouse	0
strains	0
(	0
A	0
/	0
J	0
,	0
BALB	0
/	0
cJ	0
,	0
CBA	0
/	0
J	0
,	0
C3H	0
/	0
HeJ	0
,	0
C57BL	0
/	0
6J	0
,	0
DBA	0
/	0
2J	0
,	0
SWR	0
/	0
J	0
)	0
.	0

C57BL	0
/	0
6J	0
,	0
chosen	0
as	0
a	0
"	0
prototypic	0
"	0
mouse	0
strain	0
,	0
was	0
used	0
to	0
determine	0
behavioral	0
responses	0
to	0
a	0
broad	0
range	0
(	0
5	0
-	0
500	0
mg	0
/	0
kg	0
)	0
of	0
caffeine	1
doses	0
.	0

Five	0
phenotypic	0
characteristics	0
-	0
-	0
locomotor	0
activity	0
,	0
righting	0
ability	0
,	0
clonic	3
seizure	4
induction	0
,	0
stress	0
-	0
induced	0
lethality	0
,	0
death	0
without	0
external	0
stress	0
-	0
-	0
were	0
scored	0
at	0
various	0
caffeine	1
doses	0
in	0
drug	0
-	0
naive	0
animals	0
under	0
empirically	0
optimized	0
,	0
rigidly	0
constant	0
experimental	0
conditions	0
.	0

Mice	0
(	0
n	0
=	0
12	0
for	0
each	0
point	0
)	0
received	0
single	0
IP	0
injections	0
of	0
a	0
fixed	0
volume	0
/	0
g	0
body	0
weight	0
of	0
physiological	0
saline	0
carrier	0
with	0
or	0
without	0
caffeine	1
in	0
doses	0
ranging	0
from	0
125	0
-	0
500	0
mg	0
/	0
kg	0
.	0

Loss	0
of	0
righting	0
ability	0
was	0
scored	0
at	0
1	0
,	0
3	0
,	0
5	0
min	0
post	0
dosing	0
and	0
at	0
5	0
min	0
intervals	0
thereafter	0
for	0
20	0
min	0
.	0

In	0
the	0
same	0
animals	0
the	0
occurrence	0
of	0
clonic	3
seizures	4
was	0
scored	0
as	0
to	0
time	0
of	0
onset	0
and	0
severity	0
for	0
20	0
min	0
after	0
drug	0
administration	0
.	0

When	0
these	0
proceeded	0
to	0
tonic	3
seizures	4
,	0
death	0
occurred	0
in	0
less	0
than	0
20	0
min	0
.	0

Animals	0
surviving	0
for	0
20	0
min	0
were	0
immediately	0
stressed	0
by	0
a	0
swim	0
test	0
in	0
25	0
degrees	0
C	0
water	0
,	0
and	0
death	0
-	0
producing	0
tonic	3
seizures	4
were	0
scored	0
for	0
2	0
min	0
.	0

In	0
other	0
animals	0
locomotor	0
activity	0
was	0
measured	0
15	0
or	0
60	0
min	0
after	0
caffeine	1
administration	0
.	0

By	0
any	0
single	0
behavioral	0
criterion	0
or	0
a	0
combination	0
of	0
these	0
criteria	0
,	0
marked	0
differences	0
in	0
response	0
to	0
toxic	0
caffeine	1
doses	0
were	0
observed	0
between	0
strains	0
.	0

These	0
results	0
indicate	0
that	0
behavioral	0
toxicity	3
testing	0
of	0
alkylxanthines	1
in	0
a	0
single	0
mouse	0
strain	0
may	0
be	0
misleading	0
and	0
suggest	0
that	0
toxic	0
responses	0
of	0
the	0
central	0
nervous	0
system	0
to	0
this	0
class	0
of	0
compounds	0
are	0
genetically	0
influenced	0
in	0
mammals	0
.	0

Treatment	0
of	0
ovarian	3
cancer	4
with	0
a	0
combination	0
of	0
cis	1
-	2
platinum	2
,	0
adriamycin	1
,	0
cyclophosphamide	1
and	0
hexamethylmelamine	1
.	0

During	0
the	0
last	0
2	0
1	0
/	0
2	0
years	0
,	0
38	0
patients	0
with	0
ovarian	3
cancer	4
were	0
treated	0
with	0
a	0
combination	0
of	0
cisplatinum	1
(	0
CPDD	1
)	0
,	0
50	0
mg	0
/	0
m2	0
,	0
adriamycin	1
,	0
30	0
mg	0
/	0
m2	0
,	0
cyclophosphamide	1
,	0
300	0
mg	0
/	0
m2	0
,	0
on	0
day	0
1	0
;	0
and	0
hexamethylmelamine	1
(	0
HMM	1
)	0
,	0
6	0
mg	0
/	0
kg	0
daily	0
,	0
for	0
14	0
days	0
.	0

Each	0
course	0
was	0
repeated	0
monthly	0
.	0

2	0
patients	0
had	0
stage	0
II	0
,	0
14	0
stage	0
III	0
and	0
22	0
stage	0
IV	0
disease	0
.	0

14	0
of	0
the	0
38	0
patients	0
were	0
previously	0
treated	0
with	0
chemotherapy	0
,	0
1	0
with	0
radiation	0
,	0
6	0
with	0
both	0
chemotherapy	0
and	0
radiation	0
,	0
and	0
17	0
did	0
not	0
have	0
any	0
treatment	0
before	0
CPDD	1
combination	0
.	0

31	0
of	0
the	0
38	0
cases	0
(	0
81	0
.	0
5	0
%	0
)	0
demonstrated	0
objective	0
responses	0
lasting	0
for	0
2	0
months	0
or	0
more	0
.	0

These	0
responses	0
were	0
partial	0
in	0
19	0
and	0
complete	0
in	0
12	0
cases	0
.	0

Hematologic	3
toxicity	4
was	0
moderate	0
and	0
with	0
reversible	0
anemia	3
developing	0
in	0
71	0
%	0
of	0
patients	0
.	0

Gastrointestinal	0
side	0
effects	0
from	0
CPDD	1
were	0
universal	0
.	0

HMM	1
gastrointestinal	3
toxicity	4
necessitated	0
discontinuation	0
of	0
the	0
drug	0
in	0
5	0
patients	0
.	0

Severe	0
nephrotoxicity	3
was	0
observed	0
in	0
2	0
patients	0
but	0
was	0
reversible	0
.	0

There	0
were	0
no	0
drug	0
-	0
related	0
deaths	0
.	0

Nontraumatic	0
dissecting	3
aneurysm	4
of	0
the	0
basilar	0
artery	0
.	0

A	0
case	0
of	0
nontraumatic	0
dissecting	3
aneurysm	4
of	0
the	0
basilar	0
artery	0
in	0
association	0
with	0
hypertension	3
,	0
smoke	0
,	0
and	0
oral	1
contraceptives	2
is	0
reported	0
in	0
a	0
young	0
female	0
patient	0
with	0
a	0
locked	3
-	4
in	4
syndrome	4
.	0

A	0
method	0
for	0
the	0
measurement	0
of	0
tremor	3
,	0
and	0
a	0
comparison	0
of	0
the	0
effects	0
of	0
tocolytic	0
beta	0
-	0
mimetics	0
.	0

A	0
method	0
permitting	0
measurement	0
of	0
finger	0
tremor	3
as	0
a	0
displacement	0
-	0
time	0
curve	0
is	0
described	0
,	0
using	0
a	0
test	0
system	0
with	0
simple	0
amplitude	0
calibration	0
.	0

The	0
coordinates	0
of	0
the	0
inversion	0
points	0
of	0
the	0
displacement	0
-	0
time	0
curves	0
were	0
transferred	0
through	0
graphical	0
input	0
equipment	0
to	0
punched	0
tape	0
.	0

By	0
means	0
of	0
a	0
computer	0
program	0
,	0
periods	0
and	0
amplitudes	0
of	0
tremor	3
oscillations	0
were	0
calculated	0
and	0
classified	0
.	0

The	0
event	0
frequency	0
for	0
each	0
class	0
of	0
periods	0
and	0
amplitudes	0
was	0
determined	0
.	0

The	0
actions	0
of	0
fenoterol	1
-	2
hydrobromide	2
,	0
ritodrin	1
-	2
HCl	2
and	0
placebo	0
given	0
to	0
10	0
healthy	0
subjects	0
by	0
intravenous	0
infusion	0
in	0
a	0
double	0
-	0
blind	0
crossover	0
study	0
were	0
tested	0
by	0
this	0
method	0
.	0

At	0
therapeutic	0
doses	0
both	0
substances	0
raised	0
the	0
mean	0
tremor	3
amplitude	0
to	0
about	0
three	0
times	0
the	0
control	0
level	0
.	0

At	0
the	0
same	0
time	0
,	0
the	0
mean	0
period	0
within	0
each	0
class	0
of	0
amplitudes	0
shortened	0
by	0
10	0
-	0
-	0
20	0
ms	0
,	0
whereas	0
the	0
mean	0
periods	0
calculated	0
from	0
all	0
oscillations	0
together	0
did	0
not	0
change	0
significantly	0
.	0

After	0
the	0
end	0
of	0
fenoterol	1
-	2
hydrobromide	2
infusion	0
,	0
tremor	3
amplitudes	0
decreased	0
significantly	0
faster	0
than	0
those	0
following	0
ritodrin	1
-	2
HCl	2
infusion	0
.	0

Propylthiouracil	1
-	0
induced	0
hepatic	3
damage	4
.	0

Two	0
cases	0
of	0
propylthiouracil	1
-	0
induced	0
liver	3
damage	4
have	0
been	0
observed	0
.	0

The	0
first	0
case	0
is	0
of	0
an	0
acute	0
type	0
of	0
damage	0
,	0
proven	0
by	0
rechallenge	0
;	0
the	0
second	0
presents	0
a	0
clinical	0
and	0
histologic	0
picture	0
resembling	0
chronic	3
active	4
hepatitis	4
,	0
with	0
spontaneous	0
remission	0
.	0

Studies	0
on	0
the	0
bradycardia	3
induced	0
by	0
bepridil	1
.	0

Bepridil	1
,	0
a	0
novel	0
active	0
compound	0
for	0
prophylactic	0
treatment	0
of	0
anginal	3
attacks	4
,	0
induced	0
persistent	0
bradycardia	3
and	0
a	0
non	0
-	0
specific	0
anti	0
-	0
tachycardial	3
effect	0
,	0
the	0
mechanisms	0
of	0
which	0
were	0
investigated	0
in	0
vitro	0
and	0
in	0
vivo	0
.	0

In	0
vitro	0
perfusion	0
of	0
bepridil	1
in	0
the	0
life	0
-	0
support	0
medium	0
for	0
isolated	0
sino	0
-	0
atrial	0
tissue	0
from	0
rabbit	0
heart	0
,	0
caused	0
a	0
reduction	0
in	0
action	0
potential	0
(	0
AP	0
)	0
spike	0
frequency	0
(	0
recorded	0
by	0
KCl	1
microelectrodes	0
)	0
starting	0
at	0
doses	0
of	0
5	0
X	0
10	0
(	0
-	0
6	0
)	0
M	0
.	0

This	0
effect	0
was	0
dose	0
-	0
dependent	0
up	0
to	0
concentrations	0
of	0
5	0
X	0
10	0
(	0
-	0
5	0
)	0
M	0
,	0
whereupon	0
blockade	0
of	0
sinus	0
activity	0
set	0
in	0
.	0

Bepridil	1
at	0
a	0
dose	0
of	0
5	0
X	0
10	0
(	0
-	0
6	0
)	0
M	0
,	0
induced	0
a	0
concomitant	0
reduction	0
in	0
AP	0
amplitude	0
(	0
falling	0
from	0
71	0
+	0
/	0
-	0
8	0
mV	0
to	0
47	0
+	0
/	0
-	0
6	0
mV	0
)	0
,	0
maximum	0
systolic	0
depolarization	0
velocity	0
(	0
phase	0
0	0
)	0
which	0
fell	0
from	0
1	0
.	0
85	0
+	0
/	0
-	0
0	0
.	0
35	0
V	0
/	0
s	0
to	0
0	0
.	0
84	0
+	0
/	0
-	0
0	0
.	0
28	0
V	0
/	0
s	0
,	0
together	0
with	0
maximum	0
diastolic	0
depolarization	0
velocity	0
(	0
phase	0
4	0
)	0
which	0
fell	0
from	0
38	0
+	0
/	0
-	0
3	0
mV	0
/	0
s	0
to	0
24	0
+	0
/	0
-	0
5	0
mV	0
/	0
s	0
.	0

In	0
vivo	0
injection	0
of	0
bepridil	1
at	0
a	0
dose	0
of	0
5	0
mg	0
/	0
kg	0
(	0
i	0
.	0
v	0
.	0
)	0
into	0
6	0
anaesthetized	0
dogs	0
which	0
had	0
undergone	0
ablation	0
of	0
all	0
the	0
extrinsic	0
cardiac	0
afferent	0
nerve	0
supply	0
,	0
together	0
with	0
a	0
bilateral	0
medullo	0
-	0
adrenalectomy	0
,	0
caused	0
a	0
marked	0
reduction	0
in	0
heart	0
rate	0
which	0
fell	0
from	0
98	0
.	0
7	0
+	0
/	0
-	0
4	0
.	0
2	0
beats	0
/	0
min	0
to	0
76	0
+	0
/	0
-	0
5	0
.	0
3	0
beats	0
/	0
min	0
sustained	0
for	0
more	0
than	0
45	0
min	0
.	0

It	0
is	0
concluded	0
that	0
bepridil	1
reduces	0
heart	0
rate	0
by	0
acting	0
directly	0
on	0
the	0
sinus	0
node	0
.	0

This	0
effect	0
,	0
which	0
results	0
in	0
a	0
flattening	0
of	0
the	0
phase	0
0	0
and	0
phase	0
4	0
slope	0
,	0
together	0
with	0
a	0
longer	0
AP	0
duration	0
,	0
may	0
be	0
due	0
to	0
an	0
increase	0
in	0
the	0
time	0
constants	0
of	0
slow	0
inward	0
ionic	0
currents	0
(	0
already	0
demonstrated	0
elsewhere	0
)	0
,	0
but	0
also	0
to	0
an	0
increased	0
time	0
constant	0
for	0
deactivation	0
of	0
the	0
outward	0
potassium	1
current	0
(	0
Ip	0
)	0
.	0

Hepatitis	3
and	0
renal	3
tubular	4
acidosis	4
after	0
anesthesia	0
with	0
methoxyflurane	1
.	0

A	0
69	0
-	0
year	0
-	0
old	0
man	0
operated	0
for	0
acute	3
cholecystitis	4
under	0
methoxyflurane	1
anesthesia	0
developed	0
postoperatively	0
a	0
hepatic	3
insufficiency	4
syndrome	4
and	0
renal	3
tubular	4
acidosis	4
.	0

Massive	0
bleeding	3
appeared	0
during	0
surgery	0
which	0
lasted	0
for	0
six	0
hours	0
.	0

Postoperative	0
evolution	0
under	0
supportive	0
therapy	0
was	0
favourable	0
.	0

Complete	0
recovery	0
was	0
confirmed	0
by	0
repeated	0
controls	0
performed	0
over	0
a	0
period	0
of	0
one	0
year	0
after	0
surgery	0
.	0

Pituitary	0
response	0
to	0
luteinizing	0
hormone	0
-	0
releasing	0
hormone	0
during	0
haloperidol	1
-	0
induced	0
hyperprolactinemia	3
.	0

The	0
effects	0
of	0
a	0
6	0
-	0
hour	0
infusion	0
with	0
haloperidol	1
on	0
serum	0
prolactin	0
and	0
luteinizing	0
hormone	0
(	0
LH	0
)	0
levels	0
was	0
studied	0
in	0
a	0
group	0
of	0
male	0
subjects	0
.	0

Five	0
hours	0
after	0
starting	0
the	0
infusions	0
,	0
a	0
study	0
of	0
the	0
pituitary	0
responses	0
to	0
LH	0
-	0
releasing	0
hormone	0
(	0
LH	0
-	0
RH	0
)	0
was	0
carried	0
out	0
.	0

Control	0
patients	0
received	0
infusions	0
of	0
0	0
.	0
9	0
%	0
NaCl	1
solution	0
.	0

During	0
the	0
course	0
of	0
haloperidol	1
infusions	0
,	0
significant	0
hyperprolactinemia	3
was	0
found	0
,	0
together	0
with	0
an	0
abolished	0
pituitary	0
response	0
to	0
LH	0
-	0
RH	0
,	0
as	0
compared	0
with	0
responses	0
of	0
control	0
subjects	0
.	0

Antirifampicin	0
antibodies	0
in	0
acute	0
rifampicin	1
-	0
associated	0
renal	3
failure	4
.	0

5	0
patients	0
with	0
acute	3
renal	4
failure	4
(	0
3	0
with	0
thrombopenia	3
and	0
hemolysis	3
)	0
induced	0
by	0
the	0
reintroduction	0
of	0
rifampicin	1
are	0
described	0
.	0

No	0
correlation	0
was	0
found	0
between	0
the	0
severity	0
of	0
clinical	0
manifestations	0
and	0
the	0
total	0
dose	0
taken	0
by	0
the	0
patients	0
.	0

In	0
all	0
but	0
1	0
patient	0
,	0
antirifampicin	0
antibodies	0
were	0
detected	0
.	0

Antibodies	0
suggested	0
to	0
be	0
of	0
the	0
IgM	0
class	0
were	0
detected	0
in	0
all	0
3	0
patients	0
with	0
hematological	3
disorders	4
.	0

The	0
pattern	0
of	0
non	0
-	0
specific	0
acute	3
tubular	4
necrosis	4
found	0
in	0
the	0
2	0
biopsied	0
patients	0
,	0
indistinguishable	0
from	0
that	0
of	0
ischemic	0
origin	0
,	0
raised	0
the	0
possibility	0
of	0
a	0
vascular	0
-	0
mediated	0
damage	0
.	0

In	0
3	0
patients	0
,	0
the	0
possibility	0
of	0
a	0
triggering	0
immunoallergic	0
mechanism	0
is	0
discussed	0
.	0

Cardiovascular	0
effects	0
of	0
hypotension	3
induced	0
by	0
adenosine	1
triphosphate	2
and	0
sodium	1
nitroprusside	2
on	0
dogs	0
with	0
denervated	0
hearts	0
.	0

Adenosine	1
triphosphate	2
(	0
ATP	1
)	0
and	0
sodium	1
nitroprusside	2
(	0
SNP	1
)	0
are	0
administered	0
to	0
patients	0
to	0
induce	0
and	0
control	0
hypotension	3
during	0
anesthesia	0
.	0

SNP	1
is	0
authorized	0
for	0
clinical	0
use	0
in	0
USA	0
and	0
UK	0
,	0
and	0
ATP	1
is	0
clinically	0
used	0
in	0
other	0
countries	0
such	0
as	0
Japan	0
.	0

We	0
investigated	0
how	0
these	0
two	0
drugs	0
act	0
on	0
the	0
cardiovascular	0
systems	0
of	0
20	0
dogs	0
whose	0
hearts	0
had	0
been	0
denervated	0
by	0
a	0
procedure	0
we	0
had	0
devised	0
.	0

ATP	1
(	0
10	0
dogs	0
)	0
or	0
SNP	1
(	0
10	0
dogs	0
)	0
was	0
administered	0
to	0
reduce	0
mean	0
arterial	0
pressure	0
by	0
30	0
%	0
to	0
70	0
%	0
of	0
control	0
.	0

Before	0
,	0
during	0
and	0
after	0
induced	0
hypotension	3
,	0
we	0
measured	0
major	0
cardiovascular	0
parameters	0
.	0

Hypotension	3
induced	0
by	0
ATP	1
was	0
accompanied	0
by	0
significant	0
decreases	0
in	0
mean	0
pulmonary	0
arterial	0
pressure	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
central	0
venous	0
pressure	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
left	0
ventricular	0
end	0
-	0
diastolic	0
pressure	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
total	0
peripheral	0
resistance	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
rate	0
pressure	0
product	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
total	0
body	0
oxygen	1
consumption	0
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
,	0
and	0
heart	0
rate	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
;	0
all	0
these	0
variables	0
returned	0
normal	0
within	0
30	0
min	0
after	0
ATP	1
was	0
stopped	0
.	0

Cardiac	0
output	0
did	0
not	0
change	0
.	0

During	0
hypotension	3
produced	0
by	0
SNP	1
similar	0
decreases	0
were	0
observed	0
in	0
mean	0
pulmonary	0
arterial	0
pressure	0
(	0
p	0
less	0
than	0
0	0
.	0
01	0
)	0
,	0
central	0
venous	0
pressure	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
left	0
ventricular	0
end	0
-	0
diastolic	0
pressure	0
(	0
p	0
less	0
than	0
0	0
.	0
01	0
)	0
,	0
total	0
peripheral	0
resistance	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
rate	0
pressure	0
product	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
,	0
and	0
oxygen	1
content	0
difference	0
between	0
arterial	0
and	0
mixed	0
venous	0
blood	0
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
,	0
while	0
heart	0
rate	0
(	0
p	0
less	0
than	0
0	0
.	0
001	0
)	0
and	0
cardiac	0
output	0
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
were	0
increased	0
.	0

Recoveries	0
of	0
heart	0
rate	0
and	0
left	0
ventricular	0
end	0
-	0
diastolic	0
pressure	0
were	0
not	0
shown	0
within	0
60	0
min	0
after	0
SNP	1
had	0
been	0
stopped	0
.	0

Both	0
ATP	1
and	0
SNP	1
should	0
act	0
on	0
the	0
pacemaker	0
tissue	0
of	0
the	0
heart	0
.	0

Comparative	0
study	0
:	0
Endografine	1
(	0
diatrizoate	1
)	0
,	0
Vasurix	1
polyvidone	2
(	0
acetrizoate	1
)	0
,	0
Dimer	1
-	2
X	2
(	0
iocarmate	1
)	0
and	0
Hexabrix	1
(	0
ioxaglate	1
)	0
in	0
hysterosalpingography	0
.	0

Side	0
effects	0
of	0
hysterosalpingography	0
with	0
Dimer	1
-	2
X	2
,	0
Hexabrix	1
,	0
Vasurix	1
polyvidone	2
and	0
Endografine	1
in	0
142	0
consecutive	0
patients	0
,	0
receiving	0
one	0
of	0
the	0
four	0
tested	0
media	0
were	0
evaluated	0
from	0
replies	0
to	0
postal	0
questionnaires	0
.	0

The	0
Dimer	1
-	2
X	2
group	0
had	0
a	0
higher	0
incidence	0
of	0
nausea	3
and	0
dizziness	3
.	0

The	0
Endografine	1
group	0
had	0
a	0
higher	0
incidence	0
of	0
abdominal	3
pain	4
.	0

These	0
differences	0
occur	0
especially	0
in	0
the	0
age	0
groups	0
under	0
30	0
years	0
.	0

Hexabrix	1
and	0
Vasurix	1
polyvidone	2
are	0
considered	0
the	0
best	0
contrast	1
media	2
for	0
hysterosalpingography	0
and	0
perhaps	0
because	0
of	0
its	0
low	0
toxicity	3
Hexabrix	1
should	0
be	0
preferred	0
.	0

Post	0
-	0
suxamethonium	1
pains	3
in	0
Nigerian	0
surgical	0
patients	0
.	0

Contrary	0
to	0
an	0
earlier	0
report	0
by	0
Coxon	0
,	0
scoline	1
pain	3
occurs	0
in	0
African	0
negroes	0
.	0

Its	0
incidence	0
was	0
determined	0
in	0
a	0
prospective	0
study	0
involving	0
a	0
total	0
of	0
100	0
Nigerian	0
patients	0
(	0
50	0
out	0
-	0
patients	0
and	0
50	0
in	0
-	0
patients	0
)	0
.	0

About	0
62	0
%	0
of	0
the	0
out	0
-	0
patients	0
developed	0
scoline	1
pain	3
as	0
compared	0
with	0
about	0
26	0
%	0
among	0
the	0
in	0
-	0
patients	0
.	0

The	0
abolition	0
of	0
muscle	0
fasciculations	3
(	0
by	0
0	0
.	0
075mg	0
/	0
kg	0
dose	0
of	0
Fazadinium	1
)	0
did	0
not	0
influence	0
the	0
occurrence	0
of	0
scoline	1
pain	3
.	0

Neither	0
the	0
type	0
of	0
induction	0
agent	0
(	0
Althesin	1
or	0
Thiopentone	1
)	0
nor	0
the	0
salt	0
preparation	0
of	0
suxamethonium	1
used	0
(	0
chloride	1
or	0
bromide	1
)	0
,	0
affected	0
the	0
incidence	0
of	0
scoline	1
pain	3
.	0

Invasive	0
carcinoma	3
of	4
the	4
renal	4
pelvis	4
following	0
cyclophosphamide	1
therapy	0
for	0
nonmalignant	0
disease	0
.	0

A	0
47	0
-	0
year	0
-	0
old	0
woman	0
with	0
right	0
hydroureteronephrosis	3
due	0
to	0
ureterovesical	0
junction	0
obstruction	0
had	0
gross	0
hematuria	3
after	0
being	0
treated	0
for	0
five	0
years	0
wtih	0
cyclophosphamide	1
for	0
cerebral	3
vasculitis	4
.	0

A	0
right	0
nephroureterectomy	0
was	0
required	0
for	0
control	0
of	0
bleeding	3
.	0

The	0
pathology	0
specimen	0
contained	0
clinically	0
occult	0
invasive	0
carcinoma	3
of	4
the	4
renal	4
pelvis	4
.	0

Although	0
the	0
ability	0
of	0
cyclophosphamide	1
to	0
cause	0
hemorrhagic	3
cystitis	4
and	0
urine	0
cytologic	0
abnormalities	0
indistinguishable	0
from	0
high	0
grade	0
carcinoma	3
is	0
well	0
known	0
,	0
it	0
is	0
less	0
widely	0
appreciated	0
that	0
it	0
is	0
also	0
associated	0
with	0
carcinoma	3
of	4
the	4
urinary	4
tract	4
.	0

Twenty	0
carcinomas	3
of	4
the	4
urinary	4
bladder	4
and	0
one	0
carcinoma	3
of	4
the	4
prostate	4
have	0
been	0
reported	0
in	0
association	0
with	0
its	0
use	0
.	0

The	0
present	0
case	0
is	0
the	0
first	0
carcinoma	3
of	4
the	4
renal	4
pelvis	4
reported	0
in	0
association	0
with	0
cyclophosphamide	1
treatment	0
.	0

It	0
is	0
the	0
third	0
urinary	3
tract	4
cancer	4
reported	0
in	0
association	0
with	0
cyclophosphamide	1
treatment	0
for	0
nonmalignant	0
disease	0
.	0

The	0
association	0
of	0
the	0
tumor	3
with	0
preexisting	0
hydroureteronephrosis	3
suggests	0
that	0
stasis	0
prolonged	0
and	0
intensified	0
exposure	0
of	0
upper	0
urinary	0
tract	0
epithelium	0
to	0
cyclophosphamide	1
.	0

Patients	0
who	0
are	0
candidates	0
for	0
long	0
-	0
term	0
cyclophosphamide	1
treatment	0
should	0
be	0
routinely	0
evaluated	0
for	0
obstructive	3
uropathy	4
.	0

Medial	0
changes	0
in	0
arterial	0
spasm	3
induced	0
by	0
L	1
-	2
norepinephrine	2
.	0

In	0
normal	0
rats	0
,	0
the	0
media	0
of	0
small	0
arteries	0
(	0
0	0
.	0
4	0
-	0
-	0
0	0
.	0
2	0
mm	0
in	0
diameter	0
)	0
previously	0
was	0
shown	0
to	0
contain	0
intracellular	0
vacuoles	0
,	0
identified	0
ultrastructurally	0
as	0
herniations	0
of	0
one	0
smooth	0
muscle	0
cell	0
into	0
another	0
.	0

The	0
hypothesis	0
that	0
intense	0
vasoconstriction	0
would	0
increase	0
the	0
number	0
of	0
such	0
vacuoles	0
has	0
been	0
tested	0
.	0

In	0
the	0
media	0
of	0
the	0
saphenous	0
artery	0
and	0
its	0
distal	0
branch	0
,	0
vasoconstriction	0
induced	0
by	0
L	1
-	2
norepinephrine	2
produced	0
many	0
cell	0
-	0
to	0
-	0
cell	0
hernias	3
within	0
15	0
minutes	0
.	0

At	0
1	0
day	0
their	0
number	0
was	0
reduced	0
to	0
about	0
1	0
/	0
10	0
of	0
the	0
original	0
number	0
.	0

By	0
7	0
days	0
the	0
vessel	0
was	0
almost	0
restored	0
to	0
normal	0
.	0

Triple	0
stimulation	0
over	0
1	0
day	0
induced	0
more	0
severe	0
changes	0
in	0
the	0
media	0
.	0

These	0
findings	0
suggest	0
that	0
smooth	0
muscle	0
cells	0
are	0
susceptible	0
to	0
damage	0
in	0
the	0
course	0
of	0
their	0
specific	0
function	0
.	0

The	0
experimental	0
data	0
are	0
discussed	0
in	0
relation	0
to	0
medial	0
changes	0
observed	0
in	0
other	0
instances	0
of	0
arterial	0
spasm	3
.	0

Endothelial	0
changes	0
that	0
developed	0
in	0
the	0
same	0
experimental	0
model	0
were	0
described	0
in	0
a	0
previous	0
paper	0
.	0

Bilateral	0
retinal	3
artery	4
and	4
choriocapillaris	4
occlusion	4
following	0
the	0
injection	0
of	0
long	0
-	0
acting	0
corticosteroid	1
suspensions	0
in	0
combination	0
with	0
other	0
drugs	0
:	0
I	0
.	0

Clinical	0
studies	0
.	0

Two	0
well	0
-	0
documented	0
cases	0
of	0
bilateral	0
retinal	3
artery	4
and	4
choriocapillaris	4
occlusions	4
with	0
blindness	3
following	0
head	0
and	0
neck	0
soft	0
-	0
tissue	0
injection	0
with	0
methylprednisolone	1
acetate	2
in	0
combination	0
with	0
lidocaine	1
,	0
epinephrine	1
,	0
or	0
penicillin	1
are	0
reported	0
.	0

0ne	0
case	0
had	0
only	0
a	0
unilateral	0
injection	0
.	0

The	0
acute	0
observations	0
included	0
hazy	0
sensorium	0
,	0
superior	0
gaze	0
palsy	3
,	0
pupillary	3
abnormalities	4
,	0
and	0
conjunctival	0
hemorrhages	3
with	0
edema	3
.	0

Follow	0
-	0
up	0
changes	0
showed	0
marked	0
visual	3
loss	4
,	0
constricted	0
visual	0
fields	0
,	0
optic	0
nerve	0
pallor	0
,	0
vascular	0
attenuation	0
,	0
and	0
chorioretinal	3
atrophy	4
.	0

The	0
literature	0
is	0
reviewed	0
,	0
and	0
possible	0
causes	0
are	0
discussed	0
.	0

Abnormalities	0
of	0
the	0
pupil	0
and	0
visual	0
-	0
evoked	0
potential	0
in	0
quinine	1
amblyopia	3
.	0

Total	0
blindness	3
with	0
a	0
transient	0
tonic	3
pupillary	4
response	0
,	0
denervation	0
supersensitivity	0
,	0
and	0
abnormal	0
visual	0
-	0
evoked	0
potentials	0
developed	0
in	0
a	0
54	0
-	0
year	0
-	0
old	0
man	0
after	0
the	0
use	0
of	0
quinine	1
sulfate	2
for	0
leg	3
cramps	4
.	0

He	0
later	0
recovered	0
normal	0
visual	0
acuity	0
.	0

A	0
transient	0
tonic	3
pupillary	4
response	0
,	0
denervation	0
supersensitivity	0
,	0
and	0
abnormal	0
visual	0
-	0
evoked	0
potentials	0
in	0
quinine	1
toxicity	3
,	0
to	0
our	0
knowledge	0
,	0
have	0
not	0
been	0
previously	0
reported	0
.	0

Suxamethonium	1
-	0
induced	0
jaw	3
stiffness	4
and	0
myalgia	3
associated	0
with	0
atypical	0
cholinesterase	0
:	0
case	0
report	0
.	0

An	0
11	0
-	0
year	0
-	0
old	0
boy	0
was	0
given	0
halothane	1
,	0
nitrous	1
oxide	2
and	0
oxygen	1
,	0
pancuronium	1
0	0
.	0
4	0
mg	0
and	0
suxamethonium	1
100	0
mg	0
for	0
induction	0
of	0
anaesthesia	0
.	0

In	0
response	0
to	0
this	0
a	0
marked	0
jaw	3
stiffness	4
occurred	0
which	0
lasted	0
for	0
two	0
minutes	0
and	0
the	0
anaesthesia	0
were	0
terminated	0
.	0

Four	0
hours	0
of	0
apnoea	3
ensued	0
and	0
he	0
suffered	0
generalized	0
severe	0
myalgia	3
lasting	0
for	0
one	0
week	0
.	0

He	0
was	0
found	0
to	0
have	0
atypical	0
plasma	0
cholinesterase	0
with	0
a	0
dibucaine	1
number	0
of	0
12	0
,	0
indicating	0
homozygocity	0
.	0

This	0
was	0
verified	0
by	0
study	0
of	0
the	0
family	0
.	0

The	0
case	0
shows	0
that	0
prolonged	3
jaw	4
rigidity	4
and	0
myalgia	3
may	0
occur	0
after	0
suxamethonium	1
in	0
patients	0
with	0
atypical	0
cholinesterase	0
despite	0
pretreatment	0
with	0
pancuronium	1
.	0

Indomethacin	1
-	0
induced	0
hyperkalemia	3
in	0
three	0
patients	0
with	0
gouty	3
arthritis	4
.	0

We	0
describe	0
three	0
patients	0
in	0
whom	0
severe	0
,	0
life	0
-	0
threatening	0
hyperkalemia	3
and	0
renal	3
insufficiency	4
developed	0
after	0
treatment	0
of	0
acute	0
gouty	3
arthritis	4
with	0
indomethacin	1
.	0

This	0
complication	0
may	0
result	0
from	0
an	0
inhibition	0
of	0
prostaglandin	1
synthesis	0
and	0
consequent	0
hyporeninemic	3
hypoaidosteronism	4
.	0

Careful	0
attention	0
to	0
renal	0
function	0
and	0
potassium	1
balance	0
in	0
patients	0
receiving	0
indomethacin	1
or	0
other	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
agents	0
,	0
particularly	0
in	0
those	0
patients	0
with	0
diabetes	3
mellitus	4
or	0
preexisting	0
renal	3
disease	4
,	0
will	0
help	0
prevent	0
this	0
potentially	0
serious	0
complication	0
.	0

Etomidate	1
:	0
a	0
foreshortened	0
clinical	0
trial	0
.	0

A	0
clinical	0
evaluation	0
of	0
etomidate	1
for	0
outpatient	0
cystoscopy	0
was	0
embarked	0
upon	0
.	0

Unpremedicated	0
patients	0
were	0
given	0
fentanyl	1
1	0
microgram	0
/	0
kg	0
followed	0
by	0
etomidate	1
0	0
.	0
3	0
mg	0
/	0
kg	0
.	0

Anaesthesia	0
was	0
maintained	0
with	0
intermittent	0
etomidate	1
in	0
2	0
-	0
4	0
mg	0
doses	0
.	0

Patients	0
were	0
interviewed	0
personally	0
later	0
the	0
same	0
day	0
,	0
and	0
by	0
questionnaire	0
three	0
to	0
four	0
weeks	0
later	0
.	0

The	0
trial	0
was	0
discontinued	0
after	0
20	0
cases	0
because	0
of	0
an	0
unacceptable	0
incidence	0
of	0
side	0
effects	0
.	0

Venous	0
pain	3
occurred	0
in	0
68	0
%	0
of	0
patients	0
and	0
50	0
%	0
had	0
redness	0
,	0
pain	3
or	0
swelling	3
related	0
to	0
the	0
injection	0
site	0
,	0
in	0
some	0
cases	0
lasting	0
up	0
to	0
three	0
weeks	0
after	0
anaesthesia	0
.	0

Skeletal	0
movements	0
occurred	0
in	0
50	0
%	0
of	0
patients	0
;	0
30	0
%	0
experienced	0
respiratory	3
upset	4
,	0
one	0
sufficiently	0
severe	0
to	0
necessitate	0
abandoning	0
the	0
technique	0
.	0

Nausea	3
and	0
vomiting	3
occurred	0
in	0
40	0
%	0
and	0
25	0
%	0
had	0
disturbing	0
emergence	0
psychoses	3
.	0

Levodopa	1
-	0
induced	0
dyskinesias	3
are	0
improved	0
by	0
fluoxetine	1
.	0

We	0
evaluated	0
the	0
severity	0
of	0
motor	3
disability	4
and	0
dyskinesias	3
in	0
seven	0
levodopa	1
-	0
responsive	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
after	0
an	0
acute	0
challenge	0
with	0
the	0
mixed	0
dopamine	1
agonist	0
,	0
apomorphine	1
,	0
before	0
and	0
after	0
the	0
administration	0
of	0
fluoxetine	1
(	0
20	0
mg	0
twice	0
per	0
day	0
)	0
for	0
11	0
+	0
/	0
-	0
1	0
days	0
.	0

After	0
fluoxetine	1
treatment	0
,	0
there	0
was	0
a	0
significant	0
47	0
%	0
improvement	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
of	0
apomorphine	1
-	0
induced	0
dyskinesias	3
without	0
modification	0
of	0
parkinsonian	3
motor	3
disability	4
.	0

The	0
dyskinesias	3
were	0
reduced	0
predominantly	0
in	0
the	0
lower	0
limbs	0
during	0
the	0
onset	0
and	0
disappearance	0
of	0
dystonic	3
dyskinesias	4
(	0
onset	0
-	0
and	0
end	0
-	0
of	0
-	0
dose	0
dyskinesias	3
)	0
and	0
in	0
the	0
upper	0
limbs	0
during	0
choreic	3
mid	4
-	4
dose	4
dyskinesias	4
.	0

The	0
results	0
suggest	0
that	0
increased	0
brain	0
serotoninergic	0
transmission	0
with	0
fluoxetine	1
may	0
reduce	0
levodopa	1
-	0
or	0
dopamine	1
agonist	0
-	0
induced	0
dyskinesias	3
without	0
aggravating	0
parkinsonian	3
motor	3
disability	4
.	0

A	0
large	0
population	0
-	0
based	0
follow	0
-	0
up	0
study	0
of	0
trimethoprim	1
-	2
sulfamethoxazole	2
,	0
trimethoprim	1
,	0
and	0
cephalexin	1
for	0
uncommon	0
serious	0
drug	3
toxicity	4
.	0

We	0
conducted	0
a	0
population	0
-	0
based	0
45	0
-	0
day	0
follow	0
-	0
up	0
study	0
of	0
232	0
,	0
390	0
people	0
who	0
were	0
prescribed	0
trimethoprim	1
-	2
sulfamethoxazole	2
(	0
TMP	1
-	2
SMZ	2
)	0
,	0
266	0
,	0
951	0
prescribed	0
trimethoprim	1
alone	0
,	0
and	0
196	0
,	0
397	0
prescribed	0
cephalexin	1
,	0
to	0
estimate	0
the	0
risk	0
of	0
serious	0
liver	3
,	4
blood	4
,	4
skin	4
,	4
and	4
renal	4
disorders	4
resulting	0
in	0
referral	0
or	0
hospitalization	0
associated	0
with	0
these	0
drugs	0
.	0

The	0
results	0
were	0
based	0
on	0
information	0
recorded	0
on	0
office	0
computers	0
by	0
selected	0
general	0
practitioners	0
in	0
the	0
United	0
Kingdom	0
,	0
together	0
with	0
a	0
review	0
of	0
clinical	0
records	0
.	0

The	0
risk	0
of	0
clinically	0
important	0
idiopathic	0
liver	3
disease	4
was	0
similar	0
for	0
persons	0
prescribed	0
TMP	1
-	2
SMZ	2
(	0
5	0
.	0
2	0
/	0
100	0
,	0
000	0
)	0
and	0
those	0
prescribed	0
trimethoprim	1
alone	0
(	0
3	0
.	0
8	0
/	0
100	0
,	0
000	0
)	0
.	0

The	0
risk	0
for	0
those	0
prescribed	0
cephalexin	1
was	0
somewhat	0
lower	0
(	0
2	0
.	0
0	0
/	0
100	0
,	0
000	0
)	0
.	0

0nly	0
five	0
patients	0
experienced	0
blood	0
disorders	0
,	0
one	0
of	0
whom	0
was	0
exposed	0
to	0
TMP	1
-	2
SMZ	2
;	0
of	0
seven	0
with	0
erythema	3
multiforme	4
and	0
Stevens	3
-	4
Johnson	4
syndrome	4
,	0
four	0
were	0
exposed	0
to	0
TMP	1
-	2
SMZ	2
.	0

The	0
one	0
case	0
of	0
toxic	3
epidermal	4
necrolysis	4
occurred	0
in	0
a	0
patient	0
who	0
took	0
cephalexin	1
.	0

Finally	0
,	0
only	0
five	0
cases	0
of	0
acute	0
parenchymal	0
renal	3
disease	4
occurred	0
,	0
none	0
likely	0
to	0
be	0
caused	0
by	0
a	0
study	0
drug	0
.	0

We	0
conclude	0
that	0
the	0
risk	0
of	0
the	0
serious	0
diseases	0
studied	0
is	0
small	0
for	0
the	0
three	0
agents	0
,	0
and	0
compares	0
reasonably	0
with	0
the	0
risk	0
for	0
many	0
other	0
antibiotics	0
.	0

Clinical	0
safety	0
of	0
lidocaine	1
in	0
patients	0
with	0
cocaine	1
-	0
associated	0
myocardial	3
infarction	4
.	0

STUDY	0
0BJECTIVE	0
:	0
To	0
evaluate	0
the	0
safety	0
of	0
lidocaine	1
in	0
the	0
setting	0
of	0
cocaine	1
-	0
induced	0
myocardial	3
infarction	4
(	0
MI	3
)	0
.	0

DESIGN	0
:	0
A	0
retrospective	0
,	0
multicenter	0
study	0
.	0

SETTING	0
:	0
Twenty	0
-	0
nine	0
university	0
,	0
university	0
-	0
affiliated	0
,	0
or	0
community	0
hospitals	0
during	0
a	0
6	0
-	0
year	0
period	0
(	0
total	0
of	0
117	0
cumulative	0
hospital	0
-	0
years	0
)	0
.	0

PARTICIPANTS	0
:	0
Patients	0
with	0
cocaine	1
-	0
associated	0
MI	3
who	0
received	0
lidocaine	1
in	0
the	0
emergency	0
department	0
.	0

RESULTS	0
:	0
0f	0
29	0
patients	0
who	0
received	0
lidocaine	1
in	0
the	0
setting	0
of	0
cocaine	1
-	0
associated	0
MI	3
,	0
no	0
patient	0
died	0
;	0
exhibited	0
bradydysrhythmias	3
,	0
ventricular	3
tachycardia	4
,	0
or	0
ventricular	3
fibrillation	4
;	0
or	0
experienced	0
seizures	3
after	0
administration	0
of	0
lidocaine	1
(	0
95	0
%	0
confidence	0
interval	0
,	0
0	0
%	0
to	0
11	0
%	0
)	0
.	0

C0NCLUSI0N	0
:	0
Despite	0
theoretical	0
concerns	0
that	0
lidocaine	1
may	0
enhance	0
cocaine	1
toxicity	3
,	0
the	0
use	0
of	0
lidocaine	1
in	0
patients	0
with	0
cocaine	1
-	0
associated	0
MI	3
was	0
not	0
associated	0
with	0
significant	0
cardiovascular	3
or	4
central	4
nervous	4
system	4
toxicity	4
.	0

Experimental	0
progressive	0
muscular	3
dystrophy	4
and	0
its	0
treatment	0
with	0
high	0
doses	0
anabolizing	0
agents	0
.	0

We	0
are	0
still	0
a	0
long	0
way	0
from	0
discovering	0
an	0
unequivocal	0
pathogenetic	0
interpretation	0
of	0
progressive	0
muscular	3
dystrophy	4
in	0
man	0
.	0

Noteworthy	0
efforts	0
have	0
been	0
made	0
in	0
the	0
experimental	0
field	0
;	0
a	0
recessive	0
autosomic	0
form	0
found	0
in	0
the	0
mouse	0
seems	0
to	0
bear	0
the	0
closest	0
resemblance	0
to	0
the	0
human	0
form	0
from	0
the	0
genetic	0
point	0
of	0
view	0
.	0

Myopathy	3
due	0
to	0
lack	0
of	0
vitamin	1
E	2
and	0
myopathy	3
induced	0
by	0
certain	0
viruses	0
have	0
much	0
in	0
common	0
anatomically	0
and	0
pathologically	0
with	0
the	0
human	0
form	0
.	0

The	0
authors	0
induced	0
myodystrophy	3
in	0
the	0
rat	0
by	0
giving	0
it	0
a	0
diet	0
lacking	0
in	0
vitamin	1
E	2
.	0

The	0
pharmacological	0
characteristics	0
of	0
vitamin	1
E	2
and	0
the	0
degenerative	0
changes	0
brought	0
about	0
by	0
its	0
deficiency	0
,	0
especially	0
in	0
the	0
muscles	0
,	0
are	0
illustrated	0
.	0

It	0
is	0
thus	0
confirmed	0
that	0
the	0
histological	0
characteristics	0
of	0
myopathic	3
rat	0
muscle	0
induced	0
experimentally	0
are	0
extraordinarily	0
similar	0
to	0
those	0
of	0
human	0
myopathy	3
as	0
confirmed	0
during	0
biopsies	0
performed	0
at	0
the	0
0rthopaedic	0
Traumatological	0
Centre	0
,	0
Florence	0
.	0

The	0
encouraging	0
results	0
obtained	0
in	0
various	0
authoratative	0
departments	0
in	0
myopathic	3
patients	0
by	0
using	0
anabolizing	0
steroids	1
have	0
encouraged	0
the	0
authors	0
to	0
investigate	0
the	0
beneficial	0
effects	0
of	0
one	0
anabolizing	0
agent	0
(	0
Dianabol	1
,	0
CIBA	1
)	0
at	0
high	0
doses	0
in	0
rats	0
rendered	0
myopathic	3
by	0
a	0
diet	0
deficient	0
in	0
vitamin	1
E	2
.	0

In	0
this	0
way	0
they	0
obtained	0
appreciable	0
changes	0
in	0
body	0
weight	0
(	0
increased	0
from	0
50	0
to	0
70	0
g	0
after	0
forty	0
days	0
at	0
a	0
dose	0
of	0
5	0
mg	0
per	0
day	0
of	0
anabolizing	0
agent	0
)	0
,	0
but	0
most	0
of	0
all	0
they	0
found	0
histological	0
changes	0
due	0
to	0
"	0
regenerative	0
"	0
changes	0
in	0
the	0
muscle	0
tissue	0
,	0
which	0
however	0
maintained	0
its	0
myopathic	3
characteristics	0
in	0
the	0
control	0
animals	0
that	0
were	0
not	0
treated	0
with	0
the	0
anabolizing	0
agent	0
.	0

The	0
authors	0
conclude	0
by	0
affirming	0
the	0
undoubted	0
efficacy	0
of	0
the	0
anabolizing	0
steroids	1
in	0
experimental	0
myopathic	3
disease	4
,	0
but	0
they	0
have	0
reservations	0
as	0
to	0
the	0
transfer	0
of	0
the	0
results	0
into	0
the	0
human	0
field	0
,	0
where	0
high	0
dosage	0
cannot	0
be	0
carried	0
out	0
continuously	0
because	0
of	0
the	0
effects	0
of	0
the	0
drug	0
on	0
virility	0
;	0
because	0
the	0
tissue	0
injury	0
too	0
often	0
occurs	0
at	0
an	0
irreversible	0
stage	0
vis	0
-	0
a	0
-	0
vis	0
the	0
"	0
regeneration	0
"	0
of	0
the	0
muscle	0
tissue	0
;	0
and	0
finally	0
because	0
the	0
dystrophic	0
injurious	0
agent	0
is	0
certainly	0
not	0
the	0
lack	0
of	0
vitamin	1
E	2
but	0
something	0
as	0
yet	0
unknown	0
.	0

Paclitaxel	1
3	0
-	0
hour	0
infusion	0
given	0
alone	0
and	0
combined	0
with	0
carboplatin	1
:	0
preliminary	0
results	0
of	0
dose	0
-	0
escalation	0
trials	0
.	0

Paclitaxel	1
(	0
Taxol	1
;	0
Bristol	0
-	0
Myers	0
Squibb	0
Company	0
,	0
Princeton	0
,	0
NJ	0
)	0
by	0
3	0
-	0
hour	0
infusion	0
was	0
combined	0
with	0
carboplatin	1
in	0
a	0
phase	0
I	0
/	0
II	0
study	0
directed	0
to	0
patients	0
with	0
non	3
-	4
small	4
cell	4
lung	4
cancer	4
.	0

Carboplatin	1
was	0
given	0
at	0
a	0
fixed	0
target	0
area	0
under	0
the	0
concentration	0
-	0
time	0
curve	0
of	0
6	0
.	0
0	0
by	0
the	0
Calvert	0
formula	0
,	0
whereas	0
paclitaxel	1
was	0
escalated	0
in	0
patient	0
cohorts	0
from	0
150	0
mg	0
/	0
m2	0
(	0
dose	0
level	0
I	0
)	0
to	0
175	0
,	0
200	0
,	0
225	0
,	0
and	0
250	0
mg	0
/	0
m2	0
.	0

The	0
225	0
mg	0
/	0
m2	0
level	0
was	0
expanded	0
for	0
the	0
phase	0
II	0
study	0
since	0
the	0
highest	0
level	0
achieved	0
(	0
250	0
mg	0
/	0
m2	0
)	0
required	0
modification	0
because	0
of	0
nonhematologic	0
toxicities	3
(	0
arthralgia	3
and	0
sensory	3
neuropathy	4
)	0
.	0

Therapeutic	0
effects	0
were	0
noted	0
at	0
all	0
dose	0
levels	0
,	0
with	0
objective	0
responses	0
in	0
17	0
(	0
two	0
complete	0
and	0
15	0
partial	0
regressions	0
)	0
of	0
41	0
previously	0
untreated	0
patients	0
.	0

Toxicities	3
were	0
compared	0
with	0
a	0
cohort	0
of	0
patients	0
in	0
a	0
phase	0
I	0
trial	0
of	0
paclitaxel	1
alone	0
at	0
identical	0
dose	0
levels	0
.	0

Carboplatin	1
did	0
not	0
appear	0
to	0
add	0
to	0
the	0
hematologic	3
toxicities	4
observed	0
,	0
and	0
the	0
paclitaxel	1
/	0
carboplatin	1
combination	0
could	0
be	0
dosed	0
every	0
3	0
weeks	0
.	0

The	0
dose	0
-	0
dependent	0
effect	0
of	0
misoprostol	1
on	0
indomethacin	1
-	0
induced	0
renal	3
dysfunction	4
in	0
well	0
compensated	0
cirrhosis	3
.	0

Misoprostol	1
(	0
200	0
micrograms	0
)	0
has	0
been	0
shown	0
to	0
acutely	0
counteract	0
the	0
indomethacin	1
-	0
induced	0
renal	3
dysfunction	4
in	0
well	0
compensated	0
cirrhotic	3
patients	0
.	0

The	0
aim	0
of	0
this	0
study	0
was	0
to	0
determine	0
if	0
the	0
prophylactic	0
value	0
of	0
misoprostol	1
was	0
dose	0
-	0
dependent	0
.	0

Parameters	0
of	0
renal	0
hemodynamics	0
and	0
tubular	0
sodium	1
and	0
water	0
handling	0
were	0
assessed	0
by	0
clearance	0
techniques	0
in	0
26	0
well	0
compensated	0
cirrhotic	3
patients	0
before	0
and	0
after	0
an	0
oral	0
combination	0
of	0
50	0
mg	0
of	0
indomethacin	1
and	0
various	0
doses	0
of	0
misoprostol	1
.	0

The	0
200	0
-	0
micrograms	0
dose	0
was	0
able	0
to	0
totally	0
abolish	0
the	0
deleterious	0
renal	0
effects	0
of	0
indomethacin	1
,	0
whereas	0
the	0
800	0
-	0
micrograms	0
dose	0
resulted	0
in	0
significant	0
worsening	0
of	0
renal	0
hemodynamics	0
and	0
sodium	1
retention	0
.	0

These	0
changes	0
were	0
maximal	0
in	0
the	0
hour	0
immediately	0
after	0
medications	0
and	0
slowly	0
returned	0
toward	0
base	0
-	0
line	0
levels	0
thereafter	0
.	0

These	0
results	0
suggest	0
that	0
the	0
renal	0
protective	0
effects	0
of	0
misoprostol	1
is	0
dose	0
-	0
dependent	0
.	0

However	0
,	0
until	0
this	0
apparent	0
ability	0
of	0
200	0
micrograms	0
of	0
misoprostol	1
to	0
prevent	0
the	0
adverse	0
effects	0
of	0
indomethacin	1
on	0
renal	0
function	0
is	0
confirmed	0
with	0
chronic	0
frequent	0
dosing	0
,	0
it	0
would	0
be	0
prudent	0
to	0
avoid	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
therapy	0
in	0
patients	0
with	0
cirrhosis	3
.	0

Increased	0
frequency	0
and	0
severity	0
of	0
angio	3
-	4
oedema	4
related	0
to	0
long	0
-	0
term	0
therapy	0
with	0
angiotensin	1
-	2
converting	2
enzyme	2
inhibitor	2
in	0
two	0
patients	0
.	0

Adverse	0
reactions	0
to	0
drugs	0
are	0
well	0
recognized	0
as	0
a	0
cause	0
of	0
acute	0
or	0
chronic	0
urticaria	3
,	0
and	0
angio	3
-	4
oedema	4
.	0

Angiotensin	1
-	2
converting	2
enzyme	2
(	2
ACE	2
)	2
inhibitors	2
,	0
used	0
to	0
treat	0
hypertension	3
and	0
congestive	3
heart	4
failure	4
,	0
were	0
introduced	0
in	0
Europe	0
in	0
the	0
middle	0
of	0
the	0
eighties	0
,	0
and	0
the	0
use	0
of	0
these	0
drugs	0
has	0
increased	0
progressively	0
.	0

Soon	0
after	0
the	0
introduction	0
of	0
ACE	1
inhibitors	2
,	0
acute	0
bouts	0
of	0
angio	3
-	4
oedema	4
were	0
reported	0
in	0
association	0
with	0
the	0
use	0
of	0
these	0
drugs	0
.	0

We	0
wish	0
to	0
draw	0
attention	0
to	0
the	0
possibility	0
of	0
adverse	0
reactions	0
to	0
ACE	1
inhibitors	2
after	0
long	0
-	0
term	0
use	0
and	0
in	0
patients	0
with	0
pre	0
-	0
existing	0
angio	3
-	4
oedema	4
.	0

Myoclonus	3
associated	0
with	0
lorazepam	1
therapy	0
in	0
very	0
-	0
low	0
-	0
birth	0
-	0
weight	0
infants	0
.	0

Lorazepam	1
is	0
being	0
used	0
with	0
increasing	0
frequency	0
as	0
a	0
sedative	0
in	0
the	0
newborn	0
and	0
the	0
young	0
infant	0
.	0

Concern	0
has	0
been	0
raised	0
with	0
regard	0
to	0
the	0
safety	0
of	0
lorazepam	1
in	0
this	0
age	0
group	0
,	0
especially	0
in	0
very	0
-	0
low	0
-	0
birth	0
-	0
weight	0
(	0
VLBW	0
;	0
<	0
1	0
,	0
500	0
g	0
)	0
infants	0
.	0

Three	0
young	0
infants	0
,	0
all	0
of	0
birth	0
weight	0
<	0
1	0
,	0
500	0
g	0
,	0
experienced	0
myoclonus	3
following	0
the	0
intravenous	0
administration	0
of	0
lorazepam	1
.	0

The	0
potential	0
neurotoxic	3
effects	0
of	0
the	0
drug	0
(	0
and	0
its	0
vehicle	0
)	0
in	0
this	0
population	0
are	0
discussed	0
.	0

Injectable	0
lorazepam	1
should	0
be	0
used	0
with	0
caution	0
in	0
VLBW	0
infants	0
.	0

Transvenous	0
right	0
ventricular	0
pacing	0
during	0
cardiopulmonary	0
resuscitation	0
of	0
pediatric	0
patients	0
with	0
acute	0
cardiomyopathy	3
.	0

We	0
describe	0
the	0
cardiopulmonary	0
resuscitation	0
efforts	0
on	0
five	0
patients	0
who	0
presented	0
in	0
acute	0
circulatory	3
failure	4
from	0
myocardial	3
dysfunction	4
.	0

Three	0
patients	0
had	0
acute	0
viral	0
myocarditis	3
,	0
one	0
had	0
a	0
carbamazepine	1
-	0
induced	0
acute	0
eosinophilic	3
myocarditis	4
,	0
and	0
one	0
had	0
cardiac	0
hemosiderosis	0
resulting	0
in	0
acute	0
cardiogenic	3
shock	4
.	0

All	0
patients	0
were	0
continuously	0
monitored	0
with	0
central	0
venous	0
and	0
arterial	0
catheters	0
in	0
addition	0
to	0
routine	0
noninvasive	0
monitoring	0
.	0

An	0
introducer	0
sheath	0
,	0
a	0
pacemaker	0
,	0
and	0
sterile	0
pacing	0
wires	0
were	0
made	0
readily	0
available	0
for	0
the	0
patients	0
,	0
should	0
the	0
need	0
arise	0
to	0
terminate	0
resistant	0
cardiac	0
dysrhythmias	3
.	0

All	0
patients	0
developed	0
cardiocirculatory	0
arrest	0
associated	0
with	0
extreme	0
hypotension	3
and	0
dysrhythmias	3
within	0
the	0
first	0
48	0
hours	0
of	0
their	0
admission	0
to	0
the	0
pediatric	0
intensive	0
care	0
unit	0
(	0
PICU	0
)	0
.	0

Right	0
ventricular	0
pacemaker	0
wires	0
were	0
inserted	0
in	0
all	0
of	0
them	0
during	0
cardiopulmonary	0
resuscitation	0
(	0
CPR	0
)	0
.	0

In	0
four	0
patients	0
,	0
cardiac	0
pacing	0
was	0
used	0
,	0
resulting	0
in	0
a	0
temporary	0
captured	0
rhythm	0
and	0
restoration	0
of	0
their	0
cardiac	0
output	0
.	0

These	0
patients	0
had	0
a	0
second	0
event	0
of	0
cardiac	3
arrest	4
,	0
resulting	0
in	0
death	0
,	0
within	0
10	0
to	0
60	0
minutes	0
.	0

In	0
one	0
patient	0
,	0
cardiac	0
pacing	0
was	0
not	0
used	0
,	0
because	0
he	0
converted	0
to	0
normal	0
sinus	0
rhythm	0
by	0
electrical	0
defibrillation	0
within	0
three	0
minutes	0
of	0
initiating	0
CPR	0
.	0

We	0
conclude	0
that	0
cardiac	0
pacing	0
during	0
resuscitative	0
efforts	0
in	0
pediatric	0
patients	0
suffering	0
from	0
acute	0
myocardial	3
dysfunction	4
may	0
not	0
have	0
long	0
-	0
term	0
value	0
in	0
and	0
of	0
itself	0
;	0
however	0
,	0
if	0
temporary	0
hemodynamic	0
stability	0
is	0
achieved	0
by	0
this	0
procedure	0
,	0
it	0
may	0
provide	0
additional	0
time	0
needed	0
to	0
institute	0
other	0
therapeutic	0
modalities	0
.	0

Efficacy	0
and	0
safety	0
of	0
granisetron	1
,	0
a	0
selective	0
5	1
-	2
hydroxytryptamine	2
-	0
3	0
receptor	0
antagonist	0
,	0
in	0
the	0
prevention	0
of	0
nausea	3
and	0
vomiting	3
induced	0
by	0
high	0
-	0
dose	0
cisplatin	1
.	0

PURP0SE	0
:	0
To	0
assess	0
the	0
antiemetic	0
effects	0
and	0
safety	0
profile	0
of	0
four	0
different	0
doses	0
of	0
granisetron	1
(	0
Kytril	1
;	0
SmithKline	0
Beecham	0
Pharmaceuticals	0
,	0
Philadelphia	0
,	0
PA	0
)	0
when	0
administered	0
as	0
a	0
single	0
intravenous	0
(	0
IV	0
)	0
dose	0
for	0
prophylaxis	0
of	0
cisplatin	1
-	0
induced	0
nausea	3
and	0
vomiting	3
.	0

PATIENTS	0
AND	0
METH0DS	0
:	0
0ne	0
hundred	0
eighty	0
-	0
four	0
chemotherapy	0
-	0
naive	0
patients	0
receiving	0
high	0
-	0
dose	0
cisplatin	1
(	0
81	0
to	0
120	0
mg	0
/	0
m2	0
)	0
were	0
randomized	0
to	0
receive	0
one	0
of	0
four	0
granisetron	1
doses	0
(	0
5	0
,	0
10	0
,	0
20	0
,	0
or	0
40	0
micrograms	0
/	0
kg	0
)	0
administered	0
before	0
chemotherapy	0
.	0

Patients	0
were	0
observed	0
on	0
an	0
inpatient	0
basis	0
for	0
18	0
to	0
24	0
hours	0
,	0
and	0
vital	0
signs	0
,	0
nausea	3
,	0
vomiting	3
,	0
retching	0
,	0
and	0
appetite	0
were	0
assessed	0
.	0

Safety	0
analyses	0
included	0
incidence	0
of	0
adverse	0
experiences	0
and	0
laboratory	0
parameter	0
changes	0
.	0

RESULTS	0
:	0
After	0
granisetron	1
doses	0
of	0
5	0
,	0
10	0
,	0
20	0
,	0
and	0
40	0
micrograms	0
/	0
kg	0
,	0
a	0
major	0
response	0
(	0
<	0
or	0
=	0
two	0
vomiting	3
or	0
retching	0
episodes	0
,	0
and	0
no	0
antiemetic	0
rescue	0
)	0
was	0
recorded	0
in	0
23	0
%	0
,	0
57	0
%	0
,	0
58	0
%	0
,	0
and	0
60	0
%	0
of	0
patients	0
,	0
respectively	0
,	0
and	0
a	0
complete	0
response	0
(	0
no	0
vomiting	3
or	0
retching	0
,	0
and	0
no	0
antiemetic	0
rescue	0
)	0
in	0
18	0
%	0
,	0
41	0
%	0
,	0
40	0
%	0
,	0
and	0
47	0
%	0
of	0
patients	0
,	0
respectively	0
.	0

There	0
was	0
a	0
statistically	0
longer	0
time	0
to	0
first	0
episode	0
of	0
nausea	3
(	0
P	0
=	0
.	0
0015	0
)	0
and	0
vomiting	3
(	0
P	0
=	0
.	0
0001	0
)	0
,	0
and	0
fewer	0
patients	0
were	0
administered	0
additional	0
antiemetic	0
medication	0
in	0
the	0
10	0
-	0
micrograms	0
/	0
kg	0
dosing	0
groups	0
than	0
in	0
the	0
5	0
-	0
micrograms	0
/	0
kg	0
dosing	0
group	0
.	0

As	0
granisetron	1
dose	0
increased	0
,	0
appetite	0
return	0
increased	0
(	0
P	0
=	0
.	0
040	0
)	0
.	0

Headache	3
was	0
the	0
most	0
frequently	0
reported	0
adverse	0
event	0
(	0
20	0
%	0
)	0
.	0

C0NCLUSI0N	0
:	0
A	0
single	0
10	0
-	0
,	0
20	0
-	0
,	0
or	0
40	0
-	0
micrograms	0
/	0
kg	0
dose	0
of	0
granisetron	1
was	0
effective	0
in	0
controlling	0
vomiting	3
in	0
57	0
%	0
to	0
60	0
%	0
of	0
patients	0
who	0
received	0
cisplatin	1
at	0
doses	0
greater	0
than	0
81	0
mg	0
/	0
m2	0
and	0
totally	0
prevented	0
vomiting	3
in	0
40	0
%	0
to	0
47	0
%	0
of	0
patients	0
.	0

There	0
were	0
no	0
statistically	0
significant	0
differences	0
in	0
efficacy	0
between	0
the	0
10	0
-	0
micrograms	0
/	0
kg	0
dose	0
and	0
the	0
20	0
-	0
and	0
40	0
-	0
micrograms	0
/	0
kg	0
doses	0
.	0

Granisetron	1
was	0
well	0
tolerated	0
at	0
all	0
doses	0
.	0

Adverse	0
interaction	0
between	0
clonidine	1
and	0
verapamil	1
.	0

0BJECTIVE	0
:	0
To	0
report	0
two	0
cases	0
of	0
a	0
possible	0
adverse	0
interaction	0
between	0
clonidine	1
and	0
verapamil	1
resulting	0
in	0
atrioventricular	3
(	4
AV	4
)	4
block	4
in	0
both	0
patients	0
and	0
severe	0
hypotension	3
in	0
one	0
patient	0
.	0

CASE	0
SUMMARIES	0
:	0
A	0
54	0
-	0
year	0
-	0
old	0
woman	0
with	0
hyperaldosteronism	3
was	0
treated	0
with	0
verapamil	1
480	0
mg	0
/	0
d	0
and	0
spironolactone	1
100	0
mg	0
/	0
d	0
.	0

After	0
the	0
addition	0
of	0
a	0
minimal	0
dose	0
of	0
clonidine	1
(	0
0	0
.	0
15	0
mg	0
bid	0
)	0
,	0
she	0
developed	0
complete	0
AV	3
block	4
and	0
severe	0
hypotension	3
,	0
which	0
resolved	0
upon	0
cessation	0
of	0
all	0
medications	0
.	0

A	0
65	0
-	0
year	0
-	0
old	0
woman	0
was	0
treated	0
with	0
extended	0
-	0
release	0
verapamil	1
240	0
mg	0
/	0
d	0
.	0

After	0
the	0
addition	0
of	0
clonidine	1
0	0
.	0
15	0
mg	0
bid	0
she	0
developed	0
complete	0
AV	3
block	4
,	0
which	0
resolved	0
after	0
all	0
therapy	0
was	0
stopped	0
.	0

DISCUSSI0N	0
:	0
An	0
adverse	0
interaction	0
between	0
clonidine	1
and	0
verapamil	1
has	0
not	0
been	0
reported	0
previously	0
.	0

We	0
describe	0
two	0
such	0
cases	0
and	0
discuss	0
the	0
various	0
mechanisms	0
that	0
might	0
cause	0
such	0
an	0
interaction	0
.	0

Clinicians	0
should	0
be	0
acquainted	0
with	0
this	0
possibly	0
fatal	0
interaction	0
between	0
two	0
commonly	0
used	0
antihypertensive	0
drugs	0
.	0

C0NCLUSI0NS	0
:	0
Caution	0
is	0
recommended	0
in	0
combining	0
clonidine	1
and	0
verapamil	1
therapy	0
,	0
even	0
in	0
patients	0
who	0
do	0
not	0
have	0
sinus	0
or	0
AV	0
node	0
dysfunction	0
.	0

The	0
two	0
drugs	0
may	0
act	0
synergistically	0
on	0
both	0
the	0
AV	0
node	0
and	0
the	0
peripheral	0
circulation	0
.	0

Pharmacological	0
studies	0
on	0
a	0
new	0
dihydrothienopyridine	1
calcium	2
antagonist	0
,	0
S	1
-	2
312	2
-	2
d	2
.	0

5th	0
communication	0
:	0
anticonvulsant	0
effects	0
in	0
mice	0
.	0

S	1
-	2
312	2
,	0
S	1
-	2
312	2
-	2
d	2
,	0
but	0
not	0
S	1
-	2
312	2
-	2
l	2
,	0
L	0
-	0
type	0
calcium	1
channel	0
antagonists	0
,	0
showed	0
anticonvulsant	0
effects	0
on	0
the	0
audiogenic	3
tonic	4
convulsions	4
in	0
DBA	0
/	0
2	0
mice	0
;	0
and	0
their	0
ED50	0
values	0
were	0
18	0
.	0
4	0
(	0
12	0
.	0
8	0
-	0
27	0
.	0
1	0
)	0
mg	0
/	0
kg	0
,	0
p	0
.	0
o	0
.	0
and	0
15	0
.	0
0	0
(	0
10	0
.	0
2	0
-	0
23	0
.	0
7	0
)	0
mg	0
/	0
kg	0
,	0
p	0
.	0
o	0
.	0
,	0
respectively	0
,	0
while	0
that	0
of	0
flunarizine	1
was	0
34	0
.	0
0	0
(	0
26	0
.	0
0	0
-	0
44	0
.	0
8	0
)	0
mg	0
/	0
kg	0
,	0
p	0
.	0
o	0
.	0

Although	0
moderate	0
anticonvulsant	0
effects	0
of	0
S	1
-	2
312	2
-	2
d	2
in	0
higher	0
doses	0
were	0
observed	0
against	0
the	0
clonic	0
convulsions	3
induced	0
by	0
pentylenetetrazole	1
(	0
85	0
mg	0
/	0
kg	0
,	0
s	0
.	0
c	0
.	0
)	0
or	0
bemegride	1
(	0
40	0
mg	0
/	0
kg	0
,	0
s	0
.	0
c	0
.	0
)	0
,	0
no	0
effects	0
were	0
observed	0
in	0
convulsions	3
induced	0
by	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
,	0
picrotoxin	1
,	0
or	0
electroshock	0
in	0
Slc	0
:	0
ddY	0
mice	0
.	0

S	1
-	2
312	2
-	2
d	2
may	0
be	0
useful	0
in	0
the	0
therapy	0
of	0
certain	0
types	0
of	0
human	0
epilepsy	3
.	0

Transmural	0
myocardial	3
infarction	4
with	0
sumatriptan	1
.	0

For	0
sumatriptan	1
,	0
tightness	0
in	0
the	0
chest	0
caused	0
by	0
an	0
unknown	0
mechanism	0
has	0
been	0
reported	0
in	0
3	0
-	0
5	0
%	0
of	0
users	0
.	0

We	0
describe	0
a	0
47	0
-	0
year	0
-	0
old	0
woman	0
with	0
an	0
acute	0
myocardial	3
infarction	4
after	0
administration	0
of	0
sumatriptan	1
6	0
mg	0
subcutaneously	0
for	0
cluster	3
headache	4
.	0

The	0
patient	0
had	0
no	0
history	0
of	0
underlying	0
ischaemic	3
heart	4
disease	4
or	0
Prinzmetal	3
'	4
s	4
angina	4
.	0

She	0
recovered	0
without	0
complications	0
.	0

Flumazenil	1
induces	0
seizures	3
and	0
death	0
in	0
mixed	0
cocaine	1
-	0
diazepam	1
intoxications	0
.	0

STUDY	0
HYP0THESIS	0
:	0
Administration	0
of	0
the	0
benzodiazepine	1
antagonist	0
flumazenil	1
may	0
unmask	0
seizures	3
in	0
mixed	0
cocaine	1
-	0
benzodiazepine	1
intoxication	0
.	0

DESIGN	0
:	0
Male	0
Sprague	0
-	0
Dawley	0
rats	0
received	0
100	0
mg	0
/	0
kg	0
cocaine	1
IP	0
alone	0
,	0
5	0
mg	0
/	0
kg	0
diazepam	1
alone	0
,	0
or	0
a	0
combination	0
of	0
diazepam	1
and	0
cocaine	1
.	0

Three	0
minutes	0
later	0
,	0
groups	0
were	0
challenged	0
with	0
vehicle	0
or	0
flumazenil	1
5	0
or	0
10	0
mg	0
/	0
kg	0
IP	0
.	0

Animal	0
behavior	0
,	0
seizures	3
(	0
time	0
to	0
and	0
incidence	0
)	0
,	0
death	0
(	0
time	0
to	0
and	0
incidence	0
)	0
,	0
and	0
cortical	0
EEG	0
tracings	0
were	0
recorded	0
.	0

INTERVENTI0NS	0
:	0
Administration	0
of	0
flumazenil	1
to	0
animals	0
after	0
they	0
had	0
received	0
a	0
combination	0
dose	0
of	0
cocaine	1
and	0
diazepam	1
.	0

RESULTS	0
:	0
In	0
group	0
1	0
,	0
animals	0
received	0
cocaine	1
followed	0
by	0
vehicle	0
.	0

This	0
resulted	0
in	0
100	0
%	0
developing	0
seizures	3
and	0
death	0
.	0

Group	0
2	0
received	0
diazepam	1
alone	0
followed	0
by	0
vehicle	0
.	0

Animals	0
became	0
somnolent	0
and	0
none	0
died	0
.	0

Group	0
3	0
received	0
diazepam	1
followed	0
by	0
5	0
mg	0
/	0
kg	0
flumazenil	1
.	0

Animals	0
became	0
somnolent	0
after	0
diazepam	1
and	0
then	0
active	0
after	0
flumazenil	1
administration	0
.	0

In	0
group	0
4	0
,	0
a	0
combination	0
of	0
cocaine	1
and	0
diazepam	1
was	0
administered	0
simultaneously	0
.	0

This	0
resulted	0
in	0
no	0
overt	0
or	0
EEG	0
-	0
detectable	0
seizures	3
and	0
a	0
50	0
%	0
incidence	0
of	0
death	0
.	0

Group	0
5	0
received	0
a	0
similar	0
combination	0
of	0
cocaine	1
and	0
diazepam	1
,	0
followed	0
later	0
by	0
5	0
mg	0
/	0
kg	0
flumazenil	1
.	0

This	0
resulted	0
in	0
an	0
increased	0
incidence	0
of	0
seizures	3
,	0
90	0
%	0
(	0
P	0
<	0
.	0
01	0
)	0
,	0
and	0
death	0
,	0
100	0
%	0
(	0
P	0
<	0
or	0
=	0
.	0
01	0
)	0
,	0
compared	0
with	0
group	0
4	0
.	0

Group	0
6	0
received	0
cocaine	1
and	0
diazepam	1
followed	0
by	0
10	0
mg	0
/	0
kg	0
flumazenil	1
.	0

This	0
also	0
resulted	0
in	0
an	0
increased	0
incidence	0
of	0
seizures	3
,	0
90	0
%	0
(	0
P	0
<	0
or	0
=	0
.	0
01	0
)	0
,	0
and	0
death	0
,	0
90	0
%	0
(	0
P	0
<	0
or	0
=	0
.	0
05	0
)	0
,	0
compared	0
with	0
group	0
4	0
.	0

C0NCLUSI0N	0
:	0
Flumazenil	1
can	0
unmask	0
seizures	3
and	0
increase	0
the	0
incidence	0
of	0
death	0
in	0
a	0
model	0
of	0
combined	0
cocaine	1
-	0
diazepam	1
intoxications	0
.	0

Mechanisms	0
for	0
protective	0
effects	0
of	0
free	0
radical	0
scavengers	0
on	0
gentamicin	1
-	0
mediated	0
nephropathy	3
in	0
rats	0
.	0

Studies	0
were	0
performed	0
to	0
examine	0
the	0
mechanisms	0
for	0
the	0
protective	0
effects	0
of	0
free	0
radical	0
scavengers	0
on	0
gentamicin	1
(	0
GM	1
)	0
-	0
mediated	0
nephropathy	3
.	0

Administration	0
of	0
GM	1
at	0
40	0
mg	0
/	0
kg	0
sc	0
for	0
13	0
days	0
to	0
rats	0
induced	0
a	0
significant	0
reduction	0
in	0
renal	0
blood	0
flow	0
(	0
RBF	0
)	0
and	0
inulin	0
clearance	0
(	0
CIn	0
)	0
as	0
well	0
as	0
marked	0
tubular	3
damage	4
.	0

A	0
significant	0
reduction	0
in	0
urinary	0
guanosine	1
3	2
'	2
,	2
5	2
'	2
-	2
cyclic	2
monophosphate	2
(	0
cGMP	1
)	0
excretion	0
and	0
a	0
significant	0
increase	0
in	0
renal	0
cortical	0
renin	0
and	0
endothelin	0
-	0
1	0
contents	0
were	0
also	0
observed	0
in	0
GM	1
-	0
mediated	0
nephropathy	3
.	0

Superoxide	1
dismutase	0
(	0
S0D	0
)	0
or	0
dimethylthiourea	1
(	0
DMTU	1
)	0
significantly	0
lessened	0
the	0
GM	1
-	0
induced	0
decrement	0
in	0
CIn	0
.	0

The	0
S0D	0
-	0
induced	0
increase	0
in	0
glomerular	0
filtration	0
rate	0
was	0
associated	0
with	0
a	0
marked	0
improvement	0
in	0
RBF	0
,	0
an	0
increase	0
in	0
urinary	0
cGMP	1
excretion	0
,	0
and	0
a	0
decrease	0
in	0
renal	0
renin	0
and	0
endothelin	0
-	0
1	0
content	0
.	0

S0D	0
did	0
not	0
attenuate	0
the	0
tubular	3
damage	4
.	0

In	0
contrast	0
,	0
DMTU	1
significantly	0
reduced	0
the	0
tubular	3
damage	4
and	0
lipid	0
peroxidation	0
,	0
but	0
it	0
did	0
not	0
affect	0
renal	0
hemodynamics	0
and	0
vasoactive	0
substances	0
.	0

Neither	0
S0D	0
nor	0
DMTU	1
affected	0
the	0
renal	0
cortical	0
GM	1
content	0
in	0
GM	1
-	0
treated	0
rats	0
.	0

These	0
results	0
suggest	0
that	0
1	0
)	0
both	0
S0D	0
and	0
DMTU	1
have	0
protective	0
effects	0
on	0
GM	1
-	0
mediated	0
nephropathy	3
,	0
2	0
)	0
the	0
mechanisms	0
for	0
the	0
protective	0
effects	0
differ	0
for	0
S0D	0
and	0
DMTU	1
,	0
and	0
3	0
)	0
superoxide	1
anions	0
play	0
a	0
critical	0
role	0
in	0
GM	1
-	0
induced	0
renal	0
vasoconstriction	0
.	0

Cephalothin	1
-	0
induced	0
immune	0
hemolytic	3
anemia	4
.	0

A	0
patient	0
with	0
renal	3
disease	4
developed	0
Coombs	0
-	0
positive	0
hemolytic	3
anemia	4
while	0
receiving	0
cephalothin	1
therapy	0
.	0

An	0
anti	0
-	0
cephalothin	1
IgG	0
antibody	0
was	0
detected	0
in	0
the	0
patient	0
'	0
s	0
serum	0
and	0
in	0
the	0
eluates	0
from	0
her	0
erythrocytes	0
.	0

In	0
addition	0
,	0
nonimmunologic	0
binding	0
of	0
normal	0
and	0
patient	0
'	0
s	0
serum	0
proteins	0
to	0
her	0
own	0
and	0
cephalothin	1
-	0
coated	0
normal	0
red	0
cells	0
was	0
demonstrated	0
.	0

Skin	0
tests	0
and	0
in	0
vitro	0
lymphocyte	0
stimulation	0
revealed	0
that	0
the	0
patient	0
was	0
sensitized	0
to	0
cephalothin	1
and	0
also	0
to	0
ampicillin	1
.	0

Careful	0
investigation	0
of	0
drug	0
-	0
induced	0
hemolytic	3
anemias	4
reveals	0
the	0
complexity	0
of	0
the	0
immune	0
mechanisms	0
involved	0
.	0

Assessment	0
of	0
cardiomyocyte	0
DNA	0
synthesis	0
during	0
hypertrophy	3
in	0
adult	0
mice	0
.	0

The	0
ability	0
of	0
cardiomyocytes	0
to	0
synthesize	0
DNA	0
in	0
response	0
to	0
experimentally	0
induced	0
cardiac	3
hypertrophy	4
was	0
assessed	0
in	0
adult	0
mice	0
.	0

Isoproterenol	1
delivered	0
by	0
osmotic	0
minipump	0
implantation	0
in	0
adult	0
C3Heb	0
/	0
FeJ	0
mice	0
resulted	0
in	0
a	0
46	0
%	0
increase	0
in	0
heart	0
weight	0
and	0
a	0
19	0
.	0
3	0
%	0
increase	0
in	0
cardiomyocyte	0
area	0
.	0

No	0
DNA	0
synthesis	0
,	0
as	0
assessed	0
by	0
autoradiographic	0
analysis	0
of	0
isolated	0
cardiomyocytes	0
,	0
was	0
observed	0
in	0
control	0
or	0
hypertrophic	3
hearts	4
.	0

A	0
survey	0
of	0
15	0
independent	0
inbred	0
strains	0
of	0
mice	0
revealed	0
that	0
ventricular	0
cardiomyocyte	0
nuclear	0
number	0
ranged	0
from	0
3	0
to	0
13	0
%	0
mononucleate	0
,	0
suggesting	0
that	0
cardiomyocyte	0
terminal	0
differentiation	0
is	0
influenced	0
directly	0
or	0
indirectly	0
by	0
genetic	0
background	0
.	0

To	0
determine	0
whether	0
the	0
capacity	0
for	0
reactive	0
DNA	0
synthesis	0
was	0
also	0
subject	0
to	0
genetic	0
regulation	0
,	0
cardiac	3
hypertrophy	4
was	0
induced	0
in	0
the	0
strains	0
of	0
mice	0
comprising	0
the	0
extremes	0
of	0
the	0
nuclear	0
number	0
survey	0
.	0

These	0
data	0
indicate	0
that	0
adult	0
mouse	0
atrial	0
and	0
ventricular	0
cardiomyocytes	0
do	0
not	0
synthesize	0
DNA	0
in	0
response	0
to	0
isoproterenol	1
-	0
induced	0
cardiac	3
hypertrophy	4
.	0

Central	0
cardiovascular	0
effects	0
of	0
AVP	1
and	0
ANP	0
in	0
normotensive	0
and	0
spontaneously	0
hypertensive	3
rats	0
.	0

The	0
purpose	0
of	0
the	0
present	0
study	0
was	0
to	0
compare	0
influence	0
of	0
central	0
arginine	1
vasopressin	2
(	0
AVP	1
)	0
and	0
of	0
atrial	0
natriuretic	0
peptide	0
(	0
ANP	0
)	0
on	0
control	0
of	0
arterial	0
blood	0
pressure	0
(	0
MAP	0
)	0
and	0
heart	0
rate	0
(	0
HR	0
)	0
in	0
normotensive	0
(	0
WKY	0
)	0
and	0
spontaneously	0
hypertensive	3
(	0
SHR	0
)	0
rats	0
.	0

Three	0
series	0
of	0
experiments	0
were	0
performed	0
on	0
30	0
WKY	0
and	0
30	0
SHR	0
,	0
chronically	0
instrumented	0
with	0
guide	0
tubes	0
in	0
the	0
lateral	0
ventricle	0
(	0
LV	0
)	0
and	0
arterial	0
and	0
venous	0
catheters	0
.	0

MAP	0
and	0
HR	0
were	0
monitored	0
before	0
and	0
after	0
i	0
.	0
v	0
.	0
injections	0
of	0
either	0
vehicle	0
or	0
1	0
,	0
10	0
and	0
50	0
ng	0
of	0
AVP	1
and	0
25	0
,	0
125	0
and	0
500	0
ng	0
of	0
ANP	0
.	0

Sensitivity	0
of	0
cardiac	0
component	0
of	0
baroreflex	0
(	0
CCB	0
)	0
,	0
expressed	0
as	0
a	0
slope	0
of	0
the	0
regression	0
line	0
was	0
determined	0
from	0
relationships	0
between	0
systolic	0
arterial	0
pressure	0
(	0
SAP	0
)	0
and	0
HR	0
period	0
(	0
HRp	0
)	0
during	0
phenylephrine	1
(	0
Phe	1
)	0
-	0
induced	0
hypertension	3
and	0
sodium	1
nitroprusside	2
(	0
SN	1
)	0
-	0
induced	0
hypotension	3
.	0

CCB	0
was	0
measured	0
before	0
and	0
after	0
administration	0
of	0
either	0
vehicle	0
,	0
AVP	1
,	0
ANP	0
,	0
or	0
both	0
peptides	0
together	0
.	0

Increases	0
of	0
MAP	0
occurred	0
after	0
LV	0
administration	0
of	0
1	0
,	0
10	0
and	0
50	0
ng	0
of	0
AVP	1
in	0
WKY	0
and	0
of	0
10	0
and	0
50	0
ng	0
in	0
SHR	0
.	0

ANP	0
did	0
not	0
cause	0
significant	0
changes	0
in	0
MAP	0
in	0
both	0
strains	0
as	0
compared	0
to	0
vehicle	0
,	0
but	0
it	0
abolished	0
AVP	1
-	0
induced	0
MAP	0
increase	0
in	0
WKY	0
and	0
SHR	0
.	0

CCB	0
was	0
reduced	0
in	0
WKY	0
and	0
SHR	0
after	0
LV	0
administration	0
of	0
AVP	1
during	0
SN	1
-	0
induced	0
hypotension	3
.	0

In	0
SHR	0
but	0
not	0
in	0
WKY	0
administration	0
of	0
ANP	0
,	0
AVP	1
and	0
ANP	0
+	0
AVP	1
decreased	0
CCB	0
during	0
Phe	1
-	0
induced	0
MAP	0
elevation	0
.	0

The	0
results	0
indicate	0
that	0
centrally	0
applied	0
AVP	1
and	0
ANP	0
exert	0
differential	0
effects	0
on	0
blood	0
pressure	0
and	0
baroreflex	0
control	0
of	0
heart	0
rate	0
in	0
WKY	0
and	0
SHR	0
and	0
suggest	0
interaction	0
of	0
these	0
two	0
peptides	0
in	0
blood	0
pressure	0
regulation	0
at	0
the	0
level	0
of	0
central	0
nervous	0
system	0
.	0

Cutaneous	0
exposure	0
to	0
warfarin	1
-	0
like	0
anticoagulant	0
causing	0
an	0
intracerebral	3
hemorrhage	4
:	0
a	0
case	0
report	0
.	0

A	0
case	0
of	0
intercerebral	0
hematoma	3
due	0
to	0
warfarin	1
-	0
induced	0
coagulopathy	3
is	0
presented	0
.	0

The	0
39	0
-	0
year	0
-	0
old	0
woman	0
had	0
spread	0
a	0
warfarin	1
-	0
type	0
rat	0
poison	0
around	0
her	0
house	0
weekly	0
using	0
her	0
bare	0
hands	0
,	0
with	0
no	0
washing	0
post	0
application	0
.	0

Percutaneous	0
absorption	0
of	0
warfarin	1
causing	0
coagulopathy	3
,	0
reported	0
three	0
times	0
in	0
the	0
past	0
,	0
is	0
a	0
significant	0
risk	0
if	0
protective	0
measures	0
,	0
such	0
as	0
gloves	0
,	0
are	0
not	0
used	0
.	0

An	0
adverse	0
drug	0
interaction	0
with	0
piroxicam	1
,	0
which	0
she	0
took	0
occasionally	0
,	0
may	0
have	0
exacerbated	0
the	0
coagulopathy	3
.	0

Pediatric	0
heart	0
transplantation	0
without	0
chronic	0
maintenance	0
steroids	1
.	0

From	0
1986	0
to	0
February	0
1993	0
,	0
40	0
children	0
aged	0
2	0
months	0
to	0
18	0
years	0
(	0
average	0
age	0
10	0
.	0
4	0
+	0
/	0
-	0
5	0
.	0
8	0
years	0
)	0
underwent	0
heart	0
transplantation	0
.	0

Indications	0
for	0
transplantation	0
were	0
idiopathic	3
cardiomyopathy	4
(	0
52	0
%	0
)	0
,	0
congenital	3
heart	4
disease	4
(	0
35	0
%	0
)	0
with	0
and	0
without	0
prior	0
repair	0
(	0
71	0
%	0
and	0
29	0
%	0
,	0
respectively	0
)	0
,	0
hypertrophic	3
cardiomyopathy	4
(	0
5	0
%	0
)	0
,	0
valvular	3
heart	4
disease	4
(	0
3	0
%	0
)	0
,	0
and	0
doxorubicin	1
cardiomyopathy	3
(	0
5	0
%	0
)	0
.	0

Patients	0
were	0
managed	0
with	0
cyclosporine	1
and	0
azathioprine	1
.	0

No	0
prophylaxis	0
with	0
antilymphocyte	0
globulin	0
was	0
used	0
.	0

Steroids	1
were	0
given	0
to	0
39	0
%	0
of	0
patients	0
for	0
refractory	0
rejection	0
,	0
but	0
weaning	0
was	0
always	0
attempted	0
and	0
generally	0
successful	0
(	0
64	0
%	0
)	0
.	0

Five	0
patients	0
(	0
14	0
%	0
)	0
received	0
maintenance	0
steroids	1
.	0

Four	0
patients	0
died	0
in	0
the	0
perioperative	0
period	0
and	0
one	0
died	0
4	0
months	0
later	0
.	0

There	0
have	0
been	0
no	0
deaths	0
related	0
to	0
rejection	0
or	0
infection	3
.	0

Average	0
follow	0
-	0
up	0
was	0
36	0
+	0
/	0
-	0
19	0
months	0
(	0
range	0
1	0
to	0
65	0
months	0
)	0
.	0

Cumulative	0
survival	0
is	0
88	0
%	0
at	0
5	0
years	0
.	0

In	0
patients	0
less	0
than	0
7	0
years	0
of	0
age	0
,	0
rejection	0
was	0
monitored	0
noninvasively	0
.	0

In	0
the	0
first	0
postoperative	0
month	0
,	0
89	0
%	0
of	0
patients	0
were	0
treated	0
for	0
rejection	0
.	0

Freedom	0
from	0
serious	0
infections	3
was	0
83	0
%	0
at	0
1	0
month	0
and	0
65	0
%	0
at	0
1	0
year	0
.	0

Cytomegalovirus	3
infections	4
were	0
treated	0
successfully	0
with	0
ganciclovir	1
in	0
11	0
patients	0
.	0

No	0
impairment	0
of	0
growth	0
was	0
observed	0
in	0
children	0
who	0
underwent	0
transplantation	0
compared	0
with	0
a	0
control	0
population	0
.	0

Twenty	0
-	0
one	0
patients	0
(	0
60	0
%	0
)	0
have	0
undergone	0
annual	0
catheterizations	0
and	0
no	0
sign	0
of	0
graft	0
atherosclerosis	3
has	0
been	0
observed	0
.	0

Seizures	3
occurred	0
in	0
five	0
patients	0
(	0
14	0
%	0
)	0
and	0
hypertension	3
was	0
treated	0
in	0
10	0
patients	0
(	0
28	0
%	0
)	0
.	0

No	0
patient	0
was	0
disabled	0
and	0
no	0
lymphoproliferative	3
disorder	4
was	0
observed	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0

Delirium	3
during	0
fluoxetine	1
treatment	0
.	0

A	0
case	0
report	0
.	0

The	0
correlation	0
between	0
high	0
serum	0
tricyclic	0
antidepressant	0
concentrations	0
and	0
central	0
nervous	0
system	0
side	0
effects	0
has	0
been	0
well	0
established	0
.	0

0nly	0
a	0
few	0
reports	0
exist	0
,	0
however	0
,	0
on	0
the	0
relationship	0
between	0
the	0
serum	0
concentrations	0
of	0
selective	0
serotonin	1
reuptake	0
inhibitors	0
(	0
SSRIs	0
)	0
and	0
their	0
toxic	0
effects	0
.	0

In	0
some	0
cases	0
,	0
a	0
high	0
serum	0
concentration	0
of	0
citalopram	1
(	0
>	0
600	0
nmol	0
/	0
L	0
)	0
in	0
elderly	0
patients	0
has	0
been	0
associated	0
with	0
increased	0
somnolence	3
and	0
movement	3
difficulties	4
.	0

Widespread	0
cognitive	3
disorders	4
,	0
such	0
as	0
delirium	3
,	0
have	0
not	0
been	0
previously	0
linked	0
with	0
high	0
blood	0
levels	0
of	0
SSRIs	0
.	0

In	0
this	0
report	0
,	0
we	0
describe	0
a	0
patient	0
with	0
acute	0
hyperkinetic	3
delirium	3
connected	0
with	0
a	0
high	0
serum	0
total	0
fluoxetine	1
(	0
fluoxetine	1
plus	0
desmethylfluoxetine	1
)	0
concentration	0
.	0

Pulmonary	3
edema	4
and	0
shock	3
after	0
high	0
-	0
dose	0
aracytine	1
-	2
C	2
for	0
lymphoma	3
;	0
possible	0
role	0
of	0
TNF	0
-	0
alpha	0
and	0
PAF	0
.	0

Four	0
out	0
of	0
23	0
consecutive	0
patients	0
treated	0
with	0
high	0
-	0
dose	0
Ara	1
-	2
C	2
for	0
lymphomas	3
in	0
our	0
institution	0
developed	0
a	0
strikingly	0
similar	0
syndrome	0
during	0
the	0
perfusion	0
.	0

It	0
was	0
characterized	0
by	0
the	0
onset	0
of	0
fever	3
,	0
diarrhea	3
,	0
shock	3
,	0
pulmonary	3
edema	4
,	0
acute	3
renal	4
failure	4
,	0
metabolic	3
acidosis	4
,	0
weight	3
gain	4
and	0
leukocytosis	3
.	0

Thorough	0
bacteriological	0
screening	0
failed	0
to	0
provide	0
evidence	0
of	0
infection	3
.	0

Sequential	0
biological	0
assays	0
of	0
IL	0
-	0
1	0
,	0
IL	0
-	0
2	0
,	0
TNF	0
and	0
PAF	0
were	0
performed	0
during	0
Ara	1
-	2
C	2
infusion	0
to	0
ten	0
patients	0
,	0
including	0
the	0
four	0
who	0
developed	0
the	0
syndrome	0
.	0

TNF	0
and	0
PAF	0
activity	0
was	0
found	0
in	0
the	0
serum	0
of	0
respectively	0
two	0
and	0
four	0
of	0
the	0
cases	0
,	0
but	0
not	0
in	0
the	0
six	0
controls	0
.	0

As	0
TNF	0
and	0
PAF	0
are	0
thought	0
to	0
be	0
involved	0
in	0
the	0
development	0
of	0
septic	0
shock	3
and	0
adult	3
respiratory	4
distress	4
syndrome	4
,	0
we	0
hypothesize	0
that	0
high	0
-	0
dose	0
Ara	1
-	2
C	2
may	0
be	0
associated	0
with	0
cytokine	0
release	0
.	0

Protective	0
effect	0
of	0
clentiazem	1
against	0
epinephrine	1
-	0
induced	0
cardiac	3
injury	4
in	0
rats	0
.	0

We	0
investigated	0
the	0
effects	0
of	0
clentiazem	1
,	0
a	0
1	1
,	2
5	2
-	2
benzothiazepine	2
calcium	1
antagonist	0
,	0
on	0
epinephrine	1
-	0
induced	0
cardiomyopathy	3
in	0
rats	0
.	0

With	0
2	0
-	0
week	0
chronic	0
epinephrine	1
infusion	0
,	0
16	0
of	0
30	0
rats	0
died	0
within	0
4	0
days	0
,	0
and	0
severe	0
ischemic	3
lesions	4
and	0
fibrosis	3
of	0
the	0
left	0
ventricles	0
were	0
observed	0
.	0

In	0
epinephrine	1
-	0
treated	0
rats	0
,	0
left	0
atrial	0
and	0
left	0
ventricular	0
papillary	0
muscle	0
contractile	0
responses	0
to	0
isoproterenol	1
were	0
reduced	0
,	0
but	0
responses	0
to	0
calcium	1
were	0
normal	0
or	0
enhanced	0
compared	0
to	0
controls	0
.	0

Left	0
ventricular	0
alpha	0
and	0
beta	0
adrenoceptor	0
densities	0
were	0
also	0
reduced	0
compared	0
to	0
controls	0
.	0

Treatment	0
with	0
clentiazem	1
prevented	0
epinephrine	1
-	0
induced	0
death	0
(	0
P	0
<	0
.	0
05	0
)	0
,	0
and	0
attenuated	0
the	0
ventricular	0
ischemic	3
lesions	4
and	0
fibrosis	3
,	0
in	0
a	0
dose	0
-	0
dependent	0
manner	0
.	0

Left	0
atrial	0
and	0
left	0
ventricular	0
papillary	0
muscle	0
contractile	0
responses	0
to	0
isoproterenol	1
were	0
reduced	0
compared	0
to	0
controls	0
in	0
groups	0
treated	0
with	0
clentiazem	1
alone	0
,	0
but	0
combined	0
with	0
epinephrine	1
,	0
clentiazem	1
restored	0
left	0
atrial	0
responses	0
and	0
enhanced	0
left	0
ventricular	0
papillary	0
responses	0
to	0
isoproterenol	1
.	0

0n	0
the	0
other	0
hand	0
clentiazem	1
did	0
not	0
prevent	0
epinephrine	1
-	0
induced	0
down	0
-	0
regulation	0
of	0
alpha	0
and	0
beta	0
adrenoceptors	0
.	0

Interestingly	0
,	0
clentiazem	1
,	0
infused	0
alone	0
,	0
resulted	0
in	0
decreased	0
adrenergic	0
receptor	0
densities	0
in	0
the	0
left	0
ventricle	0
.	0

Clentiazem	1
also	0
did	0
not	0
prevent	0
the	0
enhanced	0
responses	0
to	0
calcium	1
seen	0
in	0
the	0
epinephrine	1
-	0
treated	0
animals	0
,	0
although	0
the	0
high	0
dose	0
of	0
clentiazem	1
partially	0
attenuated	0
the	0
maximal	0
response	0
to	0
calcium	1
compared	0
to	0
epinephrine	1
-	0
treated	0
animals	0
.	0

In	0
conclusion	0
,	0
clentiazem	1
attenuated	0
epinephrine	1
-	0
induced	0
cardiac	3
injury	4
,	0
possibly	0
through	0
its	0
effect	0
on	0
the	0
adrenergic	0
pathway	0
.	0

Kaliuretic	0
effect	0
of	0
L	1
-	2
dopa	2
treatment	0
in	0
parkinsonian	3
patients	0
.	0

Hypokalemia	3
,	0
sometimes	0
severe	0
,	0
was	0
observed	0
in	0
some	0
L	1
-	2
dopa	2
-	0
treated	0
parkinsonian	3
patients	0
.	0

The	0
influence	0
of	0
L	1
-	2
dopa	2
on	0
the	0
renal	0
excretion	0
of	0
potassium	1
was	0
studied	0
in	0
3	0
patients	0
with	0
hypokalemia	3
and	0
in	0
5	0
normokalemic	0
patients	0
by	0
determination	0
of	0
renal	0
plasma	0
flow	0
,	0
glomerular	0
filtration	0
rate	0
,	0
plasma	0
concentration	0
of	0
potassium	1
and	0
sodium	1
as	0
well	0
as	0
urinary	0
excretion	0
of	0
potassium	1
,	0
sodium	1
and	0
aldosterone	1
.	0

L	1
-	2
Dopa	2
intake	0
was	0
found	0
to	0
cause	0
an	0
increased	0
excretion	0
of	0
potassium	1
,	0
and	0
sometimes	0
also	0
of	0
sodium	1
,	0
in	0
the	0
hypokalemic	0
but	0
not	0
in	0
the	0
normokalemic	0
patients	0
.	0

This	0
effect	0
on	0
the	0
renal	0
function	0
could	0
be	0
prohibited	0
by	0
the	0
administration	0
of	0
a	0
peripheral	0
dopa	0
decarbodylase	0
inhibitor	0
.	0

It	0
is	0
not	0
known	0
why	0
this	0
effect	0
occurred	0
in	0
some	0
individuals	0
but	0
not	0
in	0
others	0
,	0
but	0
our	0
results	0
indicate	0
a	0
correlation	0
between	0
aldosterone	1
production	0
and	0
this	0
renal	0
effect	0
of	0
L	1
-	2
dopa	2
.	0

Cocaine	1
induced	0
myocardial	3
ischemia	4
.	0

We	0
report	0
a	0
case	0
of	0
myocardial	3
ischemia	4
induced	0
by	0
cocaine	1
.	0

The	0
ischemia	3
probably	0
induced	0
by	0
coronary	3
artery	4
spasm	4
was	0
reversed	0
by	0
nitroglycerin	1
and	0
calcium	1
blocking	0
agents	0
.	0

Doxorubicin	1
-	0
induced	0
cardiotoxicity	3
monitored	0
by	0
ECG	0
in	0
freely	0
moving	0
mice	0
.	0

A	0
new	0
model	0
to	0
test	0
potential	0
protectors	0
.	0

In	0
laboratory	0
animals	0
,	0
histology	0
is	0
most	0
commonly	0
used	0
to	0
study	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
.	0

However	0
,	0
for	0
monitoring	0
during	0
treatment	0
,	0
large	0
numbers	0
of	0
animals	0
are	0
needed	0
.	0

Recently	0
we	0
developed	0
a	0
new	0
method	0
to	0
measure	0
ECG	0
values	0
in	0
freely	0
moving	0
mice	0
by	0
telemetry	0
.	0

With	0
this	0
model	0
we	0
investigated	0
the	0
effect	0
of	0
chronic	0
doxorubicin	1
administration	0
on	0
the	0
ECG	0
of	0
freely	0
moving	0
BALB	0
/	0
c	0
mice	0
and	0
the	0
efficacy	0
of	0
ICRF	1
-	2
187	2
as	0
a	0
protective	0
agent	0
.	0

The	0
ST	0
interval	0
significantly	0
widened	0
from	0
15	0
.	0
0	0
+	0
/	0
-	0
1	0
.	0
5	0
to	0
56	0
.	0
8	0
+	0
/	0
-	0
11	0
.	0
8	0
ms	0
in	0
week	0
10	0
(	0
7	0
weekly	0
doses	0
of	0
4	0
mg	0
/	0
kg	0
doxorubicin	1
given	0
i	0
.	0
v	0
.	0
plus	0
3	0
weeks	0
of	0
observation	0
)	0
.	0

The	0
ECG	0
of	0
the	0
control	0
animals	0
did	0
not	0
change	0
during	0
the	0
entire	0
study	0
.	0

After	0
sacrifice	0
the	0
hearts	0
of	0
doxorubicin	1
-	0
treated	0
animals	0
were	0
enlarged	0
and	0
the	0
atria	0
were	0
hypertrophic	3
.	0

As	0
this	0
schedule	0
exerted	0
more	0
toxicity	3
than	0
needed	0
to	0
investigate	0
protective	0
agents	0
,	0
the	0
protection	0
of	0
ICRF	1
-	2
187	2
was	0
determined	0
using	0
a	0
dose	0
schedule	0
with	0
lower	0
general	0
toxicity	3
(	0
6	0
weekly	0
doses	0
of	0
4	0
mg	0
/	0
kg	0
doxorubicin	1
given	0
i	0
.	0
v	0
.	0
plus	0
2	0
weeks	0
of	0
observation	0
)	0
.	0

0n	0
this	0
schedule	0
,	0
the	0
animals	0
'	0
hearts	0
appeared	0
normal	0
after	0
sacrifice	0
and	0
ICRF	1
-	2
187	2
(	0
50	0
mg	0
/	0
kg	0
given	0
i	0
.	0
p	0
.	0
1	0
h	0
before	0
doxorubicin	1
)	0
provided	0
almost	0
full	0
protection	0
.	0

These	0
data	0
were	0
confirmed	0
by	0
histology	0
.	0

The	0
results	0
indicate	0
that	0
this	0
new	0
model	0
is	0
very	0
sensitive	0
and	0
enables	0
monitoring	0
of	0
the	0
development	0
of	0
cardiotoxicity	3
with	0
time	0
.	0

These	0
findings	0
result	0
in	0
a	0
model	0
that	0
allows	0
the	0
testing	0
of	0
protectors	0
against	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
as	0
demonstrated	0
by	0
the	0
protection	0
provided	0
by	0
ICRF	1
-	2
187	2
.	0

Epinephrine	1
dysrhythmogenicity	0
is	0
not	0
enhanced	0
by	0
subtoxic	0
bupivacaine	1
in	0
dogs	0
.	0

Since	0
bupivacaine	1
and	0
epinephrine	1
may	0
both	0
precipitate	0
dysrhythmias	3
,	0
circulating	0
bupivacaine	1
during	0
regional	0
anesthesia	0
could	0
potentiate	0
dysrhythmogenic	0
effects	0
of	0
epinephrine	1
.	0

We	0
therefore	0
examined	0
whether	0
bupivacaine	1
alters	0
the	0
dysrhythmogenicity	0
of	0
subsequent	0
administration	0
of	0
epinephrine	1
in	0
conscious	0
,	0
healthy	0
dogs	0
and	0
in	0
anesthetized	0
dogs	0
with	0
myocardial	3
infarction	4
.	0

Forty	0
-	0
one	0
conscious	0
dogs	0
received	0
10	0
micrograms	0
.	0
kg	0
-	0
1	0
.	0
min	0
-	0
1	0
epinephrine	1
.	0

Seventeen	0
animals	0
responded	0
with	0
ventricular	3
tachycardia	4
(	0
VT	3
)	0
within	0
3	0
min	0
.	0

After	0
3	0
h	0
,	0
these	0
responders	0
randomly	0
received	0
1	0
or	0
2	0
mg	0
/	0
kg	0
bupivacaine	1
or	0
saline	0
over	0
5	0
min	0
,	0
followed	0
by	0
10	0
micrograms	0
.	0
kg	0
-	0
1	0
.	0
min	0
-	0
1	0
epinephrine	1
.	0

In	0
the	0
bupivacaine	1
groups	0
,	0
epinephrine	1
caused	0
fewer	0
prodysrhythmic	0
effects	0
than	0
without	0
bupivacaine	1
.	0

VT	3
appeared	0
in	0
fewer	0
dogs	0
and	0
at	0
a	0
later	0
time	0
,	0
and	0
there	0
were	0
more	0
sinoatrial	0
beats	0
and	0
less	0
ectopies	0
.	0

Epinephrine	1
shortened	0
QT	0
less	0
after	0
bupivacaine	1
than	0
in	0
control	0
animals	0
.	0

0ne	0
day	0
after	0
experimental	0
myocardial	3
infarction	4
,	0
six	0
additional	0
halothane	1
-	0
anesthetized	0
dogs	0
received	0
4	0
micrograms	0
.	0
kg	0
-	0
1	0
.	0
min	0
-	0
1	0
epinephrine	1
until	0
VT	3
appeared	0
.	0

After	0
45	0
min	0
,	0
1	0
mg	0
/	0
kg	0
bupivacaine	1
was	0
injected	0
over	0
5	0
min	0
,	0
again	0
followed	0
by	0
4	0
micrograms	0
.	0
kg	0
-	0
1	0
.	0
min	0
-	0
1	0
epinephrine	1
.	0

In	0
these	0
dogs	0
,	0
the	0
prodysrhythmic	0
response	0
to	0
epinephrine	1
was	0
also	0
mitigated	0
by	0
preceding	0
bupivacaine	1
.	0

Bupivacaine	1
antagonizes	0
epinephrine	1
dysrhythmogenicity	0
in	0
conscious	0
dogs	0
susceptible	0
to	0
VT	3
and	0
in	0
anesthetized	0
dogs	0
with	0
spontaneous	0
postinfarct	0
dysrhythmias	3
.	0

There	0
is	0
no	0
evidence	0
that	0
systemic	0
subtoxic	0
bupivacaine	1
administration	0
enhances	0
the	0
dysrhythmogenicity	0
of	0
subsequent	0
epinephrine	1
.	0

Milk	3
-	4
alkali	4
syndrome	4
induced	0
by	0
1	1
,	2
25	2
(	2
0H	2
)	2
2D	2
in	0
a	0
patient	0
with	0
hypoparathyroidism	3
.	0

Milk	3
-	4
alkali	4
syndrome	4
was	0
first	0
described	0
70	0
years	0
ago	0
in	0
the	0
context	0
of	0
the	0
treatment	0
of	0
peptic	3
ulcer	4
disease	4
with	0
large	0
amounts	0
of	0
calcium	1
and	0
alkali	1
.	0

Although	0
with	0
current	0
ulcer	3
therapy	0
(	0
H	0
-	0
2	0
blockers	0
,	0
omeprazole	1
,	0
and	0
sucralfate	1
)	0
,	0
the	0
frequency	0
of	0
milk	3
-	4
alkali	4
syndrome	4
has	0
decreased	0
significantly	0
,	0
the	0
classic	0
triad	0
of	0
hypercalcemia	3
,	0
alkalosis	3
,	0
and	0
renal	3
impairment	4
remains	0
the	0
hallmark	0
of	0
the	0
syndrome	0
.	0

Milk	3
-	4
alkali	4
syndrome	4
can	0
present	0
serious	0
and	0
occasionally	0
life	0
-	0
threatening	0
illness	0
unless	0
diagnosed	0
and	0
treated	0
appropriately	0
.	0

This	0
article	0
presents	0
a	0
patient	0
with	0
hypoparathyroidism	3
who	0
was	0
treated	0
with	0
calcium	1
carbonate	2
and	0
calcitriol	1
resulting	0
in	0
two	0
admissions	0
to	0
the	0
hospital	0
for	0
milk	3
-	4
alkali	4
syndrome	4
.	0

The	0
patient	0
was	0
successfully	0
treated	0
with	0
intravenous	0
pamidronate	1
on	0
his	0
first	0
admission	0
and	0
with	0
hydrocortisone	1
on	0
the	0
second	0
.	0

This	0
illustrates	0
intravenous	0
pamidronate	1
as	0
a	0
valuable	0
therapeutic	0
tool	0
when	0
milk	3
-	4
alkali	4
syndrome	4
presents	0
as	0
hypercalcemic	3
emergency	4
.	0

Famotidine	1
-	0
associated	0
delirium	3
.	0

A	0
series	0
of	0
six	0
cases	0
.	0

Famotidine	1
is	0
a	0
histamine	0
H2	0
-	0
receptor	0
antagonist	0
used	0
in	0
inpatient	0
settings	0
for	0
prevention	0
of	0
stress	0
ulcers	3
and	0
is	0
showing	0
increasing	0
popularity	0
because	0
of	0
its	0
low	0
cost	0
.	0

Although	0
all	0
of	0
the	0
currently	0
available	0
H2	0
-	0
receptor	0
antagonists	0
have	0
shown	0
the	0
propensity	0
to	0
cause	0
delirium	3
,	0
only	0
two	0
previously	0
reported	0
cases	0
have	0
been	0
associated	0
with	0
famotidine	1
.	0

The	0
authors	0
report	0
on	0
six	0
cases	0
of	0
famotidine	1
-	0
associated	0
delirium	3
in	0
hospitalized	0
patients	0
who	0
cleared	0
completely	0
upon	0
removal	0
of	0
famotidine	1
.	0

The	0
pharmacokinetics	0
of	0
famotidine	1
are	0
reviewed	0
,	0
with	0
no	0
change	0
in	0
its	0
metabolism	0
in	0
the	0
elderly	0
population	0
seen	0
.	0

The	0
implications	0
of	0
using	0
famotidine	1
in	0
elderly	0
persons	0
are	0
discussed	0
.	0

Encephalopathy	3
during	0
amitriptyline	1
therapy	0
:	0
are	0
neuroleptic	3
malignant	4
syndrome	4
and	0
serotonin	3
syndrome	4
spectrum	0
disorders	0
?	0

This	0
report	0
describes	0
a	0
case	0
of	0
encephalopathy	3
developed	0
in	0
the	0
course	0
of	0
amitriptyline	1
therapy	0
,	0
during	0
a	0
remission	0
of	0
unipolar	3
depression	4
.	0

This	0
patient	0
could	0
have	0
been	0
diagnosed	0
as	0
having	0
either	0
neuroleptic	3
malignant	4
syndrome	4
(	0
NMS	3
)	0
or	0
serotonin	3
syndrome	4
(	0
SS	3
)	0
.	0

The	0
major	0
determinant	0
of	0
the	0
symptoms	0
may	0
have	0
been	0
dopamine	1
/	0
serotonin	1
imbalance	0
in	0
the	0
central	0
nervous	0
system	0
.	0

The	0
NMS	3
-	0
like	0
encephalopathy	3
that	0
develops	0
in	0
association	0
with	0
the	0
use	0
of	0
antidepressants	0
indicates	0
that	0
NMS	3
and	0
SS	3
are	0
spectrum	0
disorders	0
induced	0
by	0
drugs	0
with	0
both	0
antidopaminergic	0
and	0
serotonergic	0
effects	0
.	0

Genetic	0
separation	0
of	0
tumor	3
growth	0
and	0
hemorrhagic	3
phenotypes	0
in	0
an	0
estrogen	1
-	0
induced	0
tumor	3
.	0

Chronic	0
administration	0
of	0
estrogen	1
to	0
the	0
Fischer	0
344	0
(	0
F344	0
)	0
rat	0
induces	0
growth	0
of	0
large	0
,	0
hemorrhagic	3
pituitary	3
tumors	4
.	0

Ten	0
weeks	0
of	0
diethylstilbestrol	1
(	0
DES	1
)	0
treatment	0
caused	0
female	0
F344	0
rat	0
pituitaries	0
to	0
grow	0
to	0
an	0
average	0
of	0
109	0
.	0
2	0
+	0
/	0
-	0
6	0
.	0
3	0
mg	0
(	0
mean	0
+	0
/	0
-	0
SE	0
)	0
versus	0
11	0
.	0
3	0
+	0
/	0
-	0
1	0
.	0
4	0
mg	0
for	0
untreated	0
rats	0
,	0
and	0
to	0
become	0
highly	0
hemorrhagic	3
.	0

The	0
same	0
DES	1
treatment	0
produced	0
no	0
significant	0
growth	0
(	0
8	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
5	0
mg	0
for	0
treated	0
females	0
versus	0
8	0
.	0
7	0
+	0
/	0
-	0
1	0
.	0
1	0
for	0
untreated	0
females	0
)	0
or	0
morphological	0
changes	0
in	0
Brown	0
Norway	0
(	0
BN	0
)	0
rat	0
pituitaries	0
.	0

An	0
F1	0
hybrid	0
of	0
F344	0
and	0
BN	0
exhibited	0
significant	0
pituitary	0
growth	0
after	0
10	0
weeks	0
of	0
DES	1
treatment	0
with	0
an	0
average	0
mass	0
of	0
26	0
.	0
3	0
+	0
/	0
-	0
0	0
.	0
7	0
mg	0
compared	0
with	0
8	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
9	0
mg	0
for	0
untreated	0
rats	0
.	0

Surprisingly	0
,	0
the	0
F1	0
hybrid	0
tumors	3
were	0
not	0
hemorrhagic	3
and	0
had	0
hemoglobin	0
content	0
and	0
outward	0
appearance	0
identical	0
to	0
that	0
of	0
BN	0
.	0

Expression	0
of	0
both	0
growth	0
and	0
morphological	0
changes	0
is	0
due	0
to	0
multiple	0
genes	0
.	0

However	0
,	0
while	0
DES	1
-	0
induced	0
pituitary	0
growth	0
exhibited	0
quantitative	0
,	0
additive	0
inheritance	0
,	0
the	0
hemorrhagic	3
phenotype	0
exhibited	0
recessive	0
,	0
epistatic	0
inheritance	0
.	0

0nly	0
5	0
of	0
the	0
160	0
F2	0
pituitaries	0
exhibited	0
the	0
hemorrhagic	3
phenotype	0
;	0
36	0
of	0
the	0
160	0
F2	0
pituitaries	0
were	0
in	0
the	0
F344	0
range	0
of	0
mass	0
,	0
but	0
31	0
of	0
these	0
were	0
not	0
hemorrhagic	3
,	0
indicating	0
that	0
the	0
hemorrhagic	3
phenotype	0
is	0
not	0
merely	0
a	0
consequence	0
of	0
extensive	0
growth	0
.	0

The	0
hemorrhagic	3
F2	0
pituitaries	0
were	0
all	0
among	0
the	0
most	0
massive	0
,	0
indicating	0
that	0
some	0
of	0
the	0
genes	0
regulate	0
both	0
phenotypes	0
.	0

Increased	0
expression	0
of	0
neuronal	0
nitric	1
oxide	2
synthase	0
in	0
bladder	0
afferent	0
pathways	0
following	0
chronic	0
bladder	3
irritation	4
.	0

Immunocytochemical	0
techniques	0
were	0
used	0
to	0
examine	0
alterations	0
in	0
the	0
expression	0
of	0
neuronal	0
nitric	1
oxide	2
synthase	0
(	0
N0S	0
)	0
in	0
bladder	0
pathways	0
following	0
acute	0
and	0
chronic	0
irritation	3
of	4
the	4
urinary	4
tract	4
of	0
the	0
rat	0
.	0

Chemical	0
cystitis	3
was	0
induced	0
by	0
cyclophosphamide	1
(	0
CYP	1
)	0
which	0
is	0
metabolized	0
to	0
acrolein	1
,	0
an	0
irritant	0
eliminated	0
in	0
the	0
urine	0
.	0

Injection	0
of	0
CYP	1
(	0
n	0
=	0
10	0
,	0
75	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
)	0
2	0
hours	0
prior	0
to	0
perfusion	0
(	0
acute	0
treatment	0
)	0
of	0
the	0
animals	0
increased	0
Fos	0
-	0
immunoreactivity	0
(	0
IR	0
)	0
in	0
neurons	0
in	0
the	0
dorsal	0
commissure	0
,	0
dorsal	0
horn	0
,	0
and	0
autonomic	0
regions	0
of	0
spinal	0
segments	0
(	0
L1	0
-	0
L2	0
and	0
L6	0
-	0
S1	0
)	0
which	0
receive	0
afferent	0
inputs	0
from	0
the	0
bladder	0
,	0
urethra	0
,	0
and	0
ureter	0
.	0

Fos	0
-	0
IR	0
in	0
the	0
spinal	0
cord	0
was	0
not	0
changed	0
in	0
rats	0
receiving	0
chronic	0
CYP	1
treatment	0
(	0
n	0
=	0
15	0
,	0
75	0
mg	0
/	0
kg	0
,	0
i	0
.	0
p	0
.	0
,	0
every	0
3rd	0
day	0
for	0
2	0
weeks	0
)	0
.	0

In	0
control	0
animals	0
and	0
in	0
animals	0
treated	0
acutely	0
with	0
CYP	1
,	0
only	0
small	0
numbers	0
of	0
N0S	0
-	0
IR	0
cells	0
(	0
0	0
.	0
5	0
-	0
0	0
.	0
7	0
cell	0
profiles	0
/	0
sections	0
)	0
were	0
detected	0
in	0
the	0
L6	0
-	0
S1	0
dorsal	0
root	0
ganglia	0
(	0
DRG	0
)	0
.	0

Chronic	0
CYP	1
administration	0
significantly	0
(	0
P	0
<	0
or	0
=	0
.	0
002	0
)	0
increased	0
bladder	0
weight	0
by	0
60	0
%	0
and	0
increased	0
(	0
7	0
-	0
to	0
11	0
-	0
fold	0
)	0
the	0
numbers	0
of	0
N0S	0
-	0
immunoreactive	0
(	0
IR	0
)	0
afferent	0
neurons	0
in	0
the	0
L6	0
-	0
S1	0
DRG	0
.	0

A	0
small	0
increase	0
(	0
1	0
.	0
5	0
-	0
fold	0
)	0
also	0
occurred	0
in	0
the	0
L1	0
DRG	0
,	0
but	0
no	0
change	0
was	0
detected	0
in	0
the	0
L2	0
and	0
L5	0
DRG	0
.	0

Bladder	0
afferent	0
cells	0
in	0
the	0
L6	0
-	0
S1	0
DRG	0
labeled	0
by	0
Fluorogold	0
(	0
40	0
microliters	0
)	0
injected	0
into	0
the	0
bladder	0
wall	0
did	0
not	0
exhibit	0
N0S	0
-	0
IR	0
in	0
control	0
animals	0
;	0
however	0
,	0
following	0
chronic	0
CYP	1
administration	0
,	0
a	0
significant	0
percentage	0
of	0
bladder	0
afferent	0
neurons	0
were	0
N0S	0
-	0
IR	0
:	0
L6	0
(	0
19	0
.	0
8	0
+	0
/	0
-	0
4	0
.	0
6	0
%	0
)	0
and	0
S1	0
(	0
25	0
.	0
3	0
+	0
/	0
-	0
2	0
.	0
9	0
%	0
)	0
.	0

These	0
results	0
indicate	0
that	0
neuronal	0
gene	0
expression	0
in	0
visceral	0
sensory	0
pathways	0
can	0
be	0
upregulated	0
by	0
chemical	0
irritation	0
of	0
afferent	0
receptors	0
in	0
the	0
urinary	0
tract	0
and	0
/	0
or	0
that	0
pathological	0
changes	0
in	0
the	0
urinary	0
tract	0
can	0
initiate	0
chemical	0
signals	0
that	0
alter	0
the	0
chemical	0
properties	0
of	0
visceral	0
afferent	0
neurons	0
.	0

Effects	0
of	0
a	0
new	0
calcium	1
antagonist	0
,	0
CD	1
-	2
832	2
,	0
on	0
isoproterenol	1
-	0
induced	0
myocardial	3
ischemia	4
in	0
dogs	0
with	0
partial	0
coronary	3
stenosis	4
.	0

Effects	0
of	0
CD	1
-	2
832	2
on	0
isoproterenol	1
(	0
IS0	1
)	0
-	0
induced	0
myocardial	3
ischemia	4
were	0
studied	0
in	0
dogs	0
with	0
partial	0
coronary	3
stenosis	4
of	0
the	0
left	0
circumflex	0
coronary	0
artery	0
and	0
findings	0
were	0
compared	0
with	0
those	0
for	0
nifedipine	1
or	0
diltiazem	1
.	0

In	0
the	0
presence	0
of	0
coronary	3
artery	4
stenosis	4
,	0
3	0
-	0
min	0
periods	0
of	0
intracoronary	0
IS0	1
infusion	0
(	0
10	0
ng	0
/	0
kg	0
/	0
min	0
)	0
increased	0
heart	0
rate	0
and	0
maximal	0
rate	0
of	0
left	0
ventricular	0
pressure	0
rise	0
,	0
which	0
resulted	0
in	0
a	0
decrease	0
in	0
percentage	0
segmental	0
shortening	0
and	0
ST	0
-	0
segment	0
elevation	0
of	0
the	0
epicardial	0
electrocardiogram	0
.	0

After	0
the	0
control	0
IS0	1
infusion	0
with	0
stenosis	3
was	0
performed	0
,	0
equihypotensive	0
doses	0
of	0
CD	1
-	2
832	2
(	0
3	0
and	0
10	0
micrograms	0
/	0
kg	0
/	0
min	0
,	0
n	0
=	0
7	0
)	0
,	0
nifedipine	1
(	0
1	0
and	0
3	0
micrograms	0
/	0
kg	0
/	0
min	0
,	0
n	0
=	0
9	0
)	0
or	0
diltiazem	1
(	0
10	0
and	0
30	0
micrograms	0
/	0
kg	0
/	0
min	0
,	0
n	0
=	0
7	0
)	0
were	0
infused	0
5	0
min	0
before	0
and	0
during	0
the	0
second	0
and	0
third	0
IS0	1
infusion	0
.	0

Both	0
CD	1
-	2
832	2
and	0
diltiazem	1
,	0
but	0
not	0
nifedipine	1
,	0
significantly	0
reduced	0
the	0
increase	0
in	0
heart	0
rate	0
induced	0
by	0
IS0	1
infusion	0
.	0

In	0
contrast	0
to	0
nifedipine	1
,	0
CD	1
-	2
832	2
(	0
10	0
micrograms	0
/	0
kg	0
/	0
min	0
)	0
prevented	0
the	0
decrease	0
in	0
percentage	0
segmental	0
shortening	0
from	0
32	0
+	0
/	0
-	0
12	0
%	0
to	0
115	0
+	0
/	0
-	0
26	0
%	0
of	0
the	0
control	0
value	0
(	0
P	0
<	0
.	0
01	0
)	0
and	0
ST	0
-	0
segment	0
elevation	0
from	0
5	0
.	0
6	0
+	0
/	0
-	0
1	0
.	0
0	0
mV	0
to	0
1	0
.	0
6	0
+	0
/	0
-	0
1	0
.	0
3	0
mV	0
(	0
P	0
<	0
.	0
01	0
)	0
at	0
3	0
min	0
after	0
IS0	1
infusion	0
with	0
stenosis	3
.	0

Diltiazem	1
(	0
30	0
micrograms	0
/	0
kg	0
/	0
min	0
)	0
also	0
prevented	0
the	0
decrease	0
in	0
percentage	0
segmental	0
shortening	0
from	0
34	0
+	0
/	0
-	0
14	0
%	0
to	0
63	0
+	0
/	0
-	0
18	0
%	0
of	0
the	0
control	0
value	0
(	0
P	0
<	0
.	0
05	0
)	0
and	0
ST	0
-	0
segment	0
elevation	0
from	0
4	0
.	0
7	0
+	0
/	0
-	0
0	0
.	0
7	0
mV	0
to	0
2	0
.	0
1	0
+	0
/	0
-	0
0	0
.	0
7	0
mV	0
(	0
P	0
<	0
.	0
01	0
)	0
at	0
3	0
min	0
after	0
IS0	1
infusion	0
with	0
stenosis	3
.	0

These	0
data	0
show	0
that	0
CD	1
-	2
832	2
improves	0
myocardial	3
ischemia	4
during	0
IS0	1
infusion	0
with	0
stenosis	3
and	0
suggest	0
that	0
the	0
negative	0
chronotropic	0
property	0
of	0
CD	1
-	2
832	2
plays	0
a	0
major	0
role	0
in	0
the	0
beneficial	0
effects	0
of	0
CD	1
-	2
832	2
.	0

The	0
effect	0
of	0
recombinant	0
human	0
insulin	0
-	0
like	0
growth	0
factor	0
-	0
I	0
on	0
chronic	0
puromycin	1
aminonucleoside	2
nephropathy	3
in	0
rats	0
.	0

We	0
recently	0
demonstrated	0
that	0
recombinant	0
hGH	0
exacerbates	0
renal	0
functional	0
and	0
structural	0
injury	0
in	0
chronic	0
puromycin	1
aminonucleoside	2
(	0
PAN	1
)	0
nephropathy	3
,	0
an	0
experimental	0
model	0
of	0
glomerular	3
disease	4
.	0

Therefore	0
,	0
we	0
examined	0
whether	0
recombinant	0
human	0
(	0
rh	0
)	0
IGF	0
-	0
I	0
is	0
a	0
safer	0
alternative	0
for	0
the	0
treatment	0
of	0
growth	3
failure	4
in	0
rats	0
with	0
chronic	0
PAN	1
nephropathy	3
.	0

The	0
glomerulopathy	3
was	0
induced	0
by	0
seven	0
serial	0
injections	0
of	0
PAN	1
over	0
12	0
wk	0
.	0

Experimental	0
animals	0
(	0
n	0
=	0
6	0
)	0
received	0
rhIGF	0
-	0
I	0
,	0
400	0
micrograms	0
/	0
d	0
,	0
whereas	0
control	0
rats	0
(	0
n	0
=	0
6	0
)	0
received	0
the	0
vehicle	0
.	0

rhIGF	0
-	0
I	0
improved	0
weight	0
gain	0
by	0
14	0
%	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
,	0
without	0
altering	0
hematocrit	0
or	0
blood	0
pressure	0
in	0
rats	0
with	0
renal	3
disease	4
.	0

Urinary	0
protein	0
excretion	0
was	0
unaltered	0
by	0
rhIGF	0
-	0
I	0
treatment	0
in	0
rats	0
with	0
chronic	0
PAN	1
nephropathy	3
.	0

After	0
12	0
wk	0
,	0
the	0
inulin	0
clearance	0
was	0
higher	0
in	0
rhIGF	0
-	0
I	0
-	0
treated	0
rats	0
,	0
0	0
.	0
48	0
+	0
/	0
-	0
0	0
.	0
08	0
versus	0
0	0
.	0
24	0
+	0
/	0
-	0
0	0
.	0
06	0
mL	0
/	0
min	0
/	0
100	0
g	0
of	0
body	0
weight	0
in	0
untreated	0
PAN	1
nephropathy	3
animals	0
,	0
p	0
<	0
0	0
.	0
05	0
.	0

The	0
improvement	0
in	0
GFR	0
was	0
not	0
associated	0
with	0
enhanced	0
glomerular	3
hypertrophy	4
or	0
increased	0
segmental	0
glomerulosclerosis	3
,	0
tubulointerstitial	3
injury	4
,	0
or	0
renal	0
cortical	0
malondialdehyde	1
content	0
.	0

In	0
rats	0
with	0
PAN	1
nephropathy	3
,	0
administration	0
of	0
rhIGF	0
-	0
I	0
increased	0
IGF	0
-	0
I	0
and	0
GH	0
receptor	0
gene	0
expression	0
,	0
without	0
altering	0
the	0
steady	0
state	0
level	0
of	0
IGF	0
-	0
I	0
receptor	0
mRNA	0
.	0

In	0
normal	0
rats	0
with	0
intact	0
kidneys	0
,	0
rhIGF	0
-	0
I	0
administration	0
(	0
n	0
=	0
4	0
)	0
did	0
not	0
alter	0
weight	0
gain	0
,	0
blood	0
pressure	0
,	0
proteinuria	3
,	0
GFR	0
,	0
glomerular	0
planar	0
area	0
,	0
renal	0
cortical	0
malondialdehyde	1
content	0
,	0
or	0
glomerular	0
or	0
tubulointerstitial	3
damage	4
,	0
compared	0
with	0
untreated	0
animals	0
(	0
n	0
=	0
4	0
)	0
.	0

rhIGF	0
-	0
I	0
treatment	0
reduced	0
the	0
steady	0
state	0
renal	0
IGF	0
-	0
I	0
mRNA	0
level	0
but	0
did	0
not	0
modify	0
gene	0
expression	0
of	0
the	0
IGF	0
-	0
I	0
or	0
GH	0
receptors	0
.	0

We	0
conclude	0
that	0
:	0
1	0
)	0
administration	0
of	0
rhIGF	0
-	0
I	0
improves	0
growth	0
and	0
GFR	0
in	0
rats	0
with	0
chronic	0
PAN	1
nephropathy	3
and	0
2	0
)	0
unlike	0
rhGH	0
,	0
long	0
-	0
term	0
use	0
of	0
rhIGF	0
-	0
I	0
does	0
not	0
worsen	0
renal	0
functional	0
and	0
structural	0
injury	0
in	0
this	0
disease	0
model	0
.	0

Nefiracetam	1
(	0
DM	1
-	2
9384	2
)	0
reverses	0
apomorphine	1
-	0
induced	0
amnesia	3
of	0
a	0
passive	0
avoidance	0
response	0
:	0
delayed	0
emergence	0
of	0
the	0
memory	0
retention	0
effects	0
.	0

Nefiracetam	1
is	0
a	0
novel	0
pyrrolidone	1
derivative	0
which	0
attenuates	0
scopolamine	1
-	0
induced	0
learning	3
and	4
post	4
-	4
training	4
consolidation	4
deficits	4
.	0

Given	0
that	0
apomorphine	1
inhibits	0
passive	0
avoidance	0
retention	0
when	0
given	0
during	0
training	0
or	0
in	0
a	0
defined	0
10	0
-	0
12h	0
post	0
-	0
training	0
period	0
,	0
we	0
evaluated	0
the	0
ability	0
of	0
nefiracetam	1
to	0
attenuate	0
amnesia	3
induced	0
by	0
dopaminergic	0
agonism	0
.	0

A	0
step	0
-	0
down	0
passive	0
avoidance	0
paradigm	0
was	0
employed	0
and	0
nefiracetam	1
(	0
3	0
mg	0
/	0
kg	0
)	0
and	0
apomorphine	1
(	0
0	0
.	0
5	0
mg	0
/	0
kg	0
)	0
were	0
given	0
alone	0
or	0
in	0
combination	0
during	0
training	0
and	0
at	0
the	0
10	0
-	0
12h	0
post	0
-	0
training	0
period	0
of	0
consolidation	0
.	0

Co	0
-	0
administration	0
of	0
nefiracetam	1
and	0
apomorphine	1
during	0
training	0
or	0
10h	0
thereafter	0
produced	0
no	0
significant	0
anti	0
-	0
amnesic	0
effect	0
.	0

However	0
,	0
administration	0
of	0
nefiracetam	1
during	0
training	0
completely	0
reversed	0
the	0
amnesia	3
induced	0
by	0
apomorphine	1
at	0
the	0
10h	0
post	0
-	0
training	0
time	0
and	0
the	0
converse	0
was	0
also	0
true	0
.	0

These	0
effects	0
were	0
not	0
mediated	0
by	0
a	0
dopaminergic	0
mechanism	0
as	0
nefiracetam	1
,	0
at	0
millimolar	0
concentrations	0
,	0
failed	0
to	0
displace	0
either	0
[	0
3H	0
]	0
SCH	1
23390	2
or	0
[	0
3H	0
]	0
spiperone	1
binding	0
from	0
D1	0
or	0
D2	0
dopamine	1
receptor	0
subtypes	0
,	0
respectively	0
.	0

It	0
is	0
suggested	0
that	0
nefiracetam	1
augments	0
molecular	0
processes	0
in	0
the	0
early	0
stages	0
of	0
events	0
which	0
ultimately	0
lead	0
to	0
consolidation	0
of	0
memory	0
.	0

Phenytoin	1
encephalopathy	3
as	0
probable	0
idiosyncratic	0
reaction	0
:	0
case	0
report	0
.	0

A	0
case	0
of	0
phenytoin	1
(	0
DPH	1
)	0
encephalopathy	3
with	0
increasing	0
seizures	3
and	0
EEG	0
and	0
mental	0
changes	0
is	0
described	0
.	0

Despite	0
adequate	0
oral	0
dosage	0
of	0
DPH	1
(	0
5	0
mg	0
/	0
kg	0
/	0
daily	0
)	0
the	0
plasma	0
level	0
was	0
very	0
low	0
(	0
2	0
.	0
8	0
microgramg	0
/	0
ml	0
)	0
.	0

The	0
encephalopathy	3
was	0
probably	0
an	0
idiosyncratic	0
and	0
not	0
toxic	0
or	0
allergic	0
reaction	0
.	0

In	0
fact	0
the	0
concentration	0
of	0
free	0
DPH	1
was	0
normal	0
,	0
the	0
patient	0
presented	0
a	0
retarded	0
morbilliform	0
rash	3
during	0
DPH	1
treatment	0
,	0
the	0
protidogram	0
was	0
normal	0
,	0
and	0
an	0
intradermic	0
DPH	1
injection	0
had	0
no	0
local	0
effect	0
.	0

The	0
authors	0
conclude	0
that	0
in	0
a	0
patient	0
starting	0
DPH	1
treatment	0
an	0
unexpected	0
increase	0
in	0
seizures	3
,	0
with	0
EEG	0
and	0
mental	0
changes	0
occurring	0
simultaneously	0
,	0
should	0
alert	0
the	0
physician	0
to	0
the	0
possible	0
need	0
for	0
eliminating	0
DPH	1
from	0
the	0
therapeutic	0
regimen	0
,	0
even	0
if	0
plasma	0
concentrations	0
are	0
low	0
.	0

Prevention	0
and	0
treatment	0
of	0
endometrial	3
disease	4
in	0
climacteric	0
women	0
receiving	0
oestrogen	1
therapy	0
.	0

The	0
treatment	0
regimens	0
are	0
described	0
in	0
74	0
patients	0
with	0
endometrial	3
disease	4
among	0
850	0
climacteric	0
women	0
receiving	0
oestrogen	1
therapy	0
.	0

Cystic	0
hyperplasia	3
was	0
associated	0
with	0
unopposed	0
oestrogen	1
therapy	0
without	0
progestagen	1
.	0

Two	0
courses	0
of	0
21	0
days	0
of	0
5	0
mg	0
norethisterone	1
daily	0
caused	0
reversion	0
to	0
normal	0
in	0
all	0
57	0
cases	0
of	0
cystic	0
hyperplasia	3
and	0
6	0
of	0
the	0
8	0
cases	0
of	0
atypical	0
hyperplasia	3
.	0

4	0
cases	0
of	0
endometrial	3
carcinoma	4
referred	0
from	0
elsewhere	0
demonstrated	0
the	0
problems	0
of	0
inappropriate	0
and	0
unsupervised	0
unopposed	0
oestrogen	1
therapy	0
and	0
the	0
difficulty	0
in	0
distinguishing	0
severe	0
hyperplasia	3
from	0
malignancy	3
.	0

Cyclical	0
low	0
-	0
dose	0
oestrogen	1
therapy	0
with	0
7	0
-	0
-	0
13	0
days	0
of	0
progestagen	1
does	0
not	0
seem	0
to	0
increase	0
the	0
risk	0
of	0
endometrial	3
hyperplasia	4
or	0
carcinoma	3
.	0

Effects	0
of	0
exercise	0
on	0
the	0
severity	0
of	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
.	0

The	0
effect	0
of	0
exercise	0
on	0
the	0
severity	0
of	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
was	0
studied	0
in	0
male	0
rats	0
.	0

Ninety	0
-	0
three	0
rats	0
were	0
randomly	0
divided	0
into	0
three	0
groups	0
.	0

The	0
exercise	0
-	0
isoproterenol	1
(	0
E	0
-	0
1	0
)	0
and	0
exercise	0
control	0
(	0
EC	0
)	0
groups	0
exercised	0
daily	0
for	0
thirty	0
days	0
on	0
a	0
treadmill	0
at	0
1	0
mph	0
,	0
2	0
%	0
grade	0
while	0
animals	0
of	0
the	0
sedentary	0
-	0
isoproterenol	1
(	0
S	0
-	0
I	0
)	0
group	0
remained	0
sedentary	0
.	0

Eight	0
animals	0
were	0
assigned	0
to	0
the	0
sedentary	0
control	0
(	0
SC	0
)	0
group	0
which	0
remained	0
sedentary	0
throughout	0
the	0
experimental	0
period	0
.	0

Forty	0
-	0
eight	0
hours	0
after	0
the	0
final	0
exercise	0
period	0
,	0
S	0
-	0
I	0
and	0
E	0
-	0
I	0
animals	0
received	0
a	0
single	0
subcutaneous	0
injection	0
of	0
isoproterenol	1
(	0
250	0
mg	0
/	0
kg	0
body	0
weight	0
)	0
.	0

Animals	0
of	0
the	0
S	0
-	0
I	0
group	0
exhibited	0
significantly	0
(	0
Pp	0
less	0
than	0
0	0
.	0
05	0
)	0
greater	0
mortality	0
from	0
the	0
effects	0
of	0
isoproterenol	1
than	0
animals	0
of	0
the	0
E	0
-	0
I	0
group	0
.	0

Serum	0
CPK	0
activity	0
for	0
E	0
-	0
I	0
animals	0
was	0
significantly	0
(	0
p	0
less	0
than	0
0	0
.	0
05	0
)	0
greater	0
than	0
for	0
animals	0
in	0
the	0
S	0
-	0
I	0
and	0
EC	0
groups	0
twenty	0
hours	0
following	0
isoproterenol	1
injection	0
.	0

No	0
statistically	0
significant	0
differences	0
were	0
observed	0
between	0
the	0
two	0
isoproterenol	1
treated	0
groups	0
for	0
severity	0
of	0
the	0
induced	0
lesions	0
,	0
changes	0
in	0
heart	0
weight	0
,	0
or	0
heart	0
weight	0
to	0
body	0
weight	0
ratios	0
.	0

The	0
results	0
indicated	0
that	0
exercise	0
reduced	0
the	0
mortality	0
associated	0
with	0
the	0
effects	0
of	0
large	0
dosages	0
of	0
isoproterenol	1
but	0
had	0
little	0
on	0
the	0
severity	0
of	0
the	0
infarction	3
.	0

Human	0
corticotropin	1
-	0
releasing	0
hormone	0
and	0
thyrotropin	1
-	0
releasing	0
hormone	0
modulate	0
the	0
hypercapnic	3
ventilatory	0
response	0
in	0
humans	0
.	0

Human	0
corticotropin	1
-	0
releasing	0
hormone	0
(	0
hCRH	0
)	0
and	0
thyrotropin	1
-	0
releasing	0
hormone	0
(	0
TRH	0
)	0
are	0
known	0
to	0
stimulate	0
ventilation	0
after	0
i	0
.	0
v	0
.	0
administration	0
in	0
humans	0
.	0

In	0
a	0
placebo	0
-	0
controlled	0
,	0
single	0
-	0
blind	0
study	0
we	0
aimed	0
to	0
clarify	0
if	0
both	0
peptides	0
act	0
by	0
altering	0
central	0
chemosensitivity	0
.	0

Two	0
subsequent	0
C02	1
-	0
rebreathing	0
tests	0
were	0
performed	0
in	0
healthy	0
young	0
volunteers	0
.	0

During	0
the	0
first	0
test	0
0	0
.	0
9	0
%	0
NaCl	1
was	0
given	0
i	0
.	0
v	0
.	0
;	0
during	0
the	0
second	0
test	0
200	0
micrograms	0
of	0
hCRH	0
(	0
n	0
=	0
12	0
)	0
or	0
400	0
micrograms	0
of	0
TRH	0
(	0
n	0
=	0
6	0
)	0
was	0
administered	0
i	0
.	0
v	0
.	0
Nine	0
subjects	0
received	0
0	0
.	0
9	0
%	0
NaCl	1
i	0
.	0
v	0
.	0
during	0
both	0
rebreathing	0
manoeuvres	0
.	0

The	0
C02	1
-	0
response	0
curves	0
for	0
the	0
two	0
tests	0
were	0
compared	0
within	0
the	0
same	0
subject	0
.	0

In	0
the	0
hCRH	0
group	0
a	0
marked	0
parallel	0
shift	0
of	0
the	0
C02	1
-	0
response	0
curve	0
to	0
the	0
left	0
was	0
observed	0
after	0
hCRH	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
.	0

The	0
same	0
effect	0
occurred	0
following	0
TRH	0
but	0
was	0
less	0
striking	0
(	0
P	0
=	0
0	0
.	0
05	0
)	0
.	0

hCRH	0
and	0
TRH	0
caused	0
a	0
reduction	0
in	0
the	0
C02	1
threshold	0
.	0

The	0
C02	1
-	0
response	0
curves	0
in	0
the	0
control	0
group	0
were	0
nearly	0
identical	0
.	0

The	0
results	0
indicate	0
an	0
additive	0
effect	0
of	0
both	0
releasing	0
hormones	0
on	0
the	0
hypercapnic	3
ventilatory	0
response	0
in	0
humans	0
,	0
presumably	0
independent	0
of	0
central	0
chemosensitivity	0
.	0

Lamivudine	1
is	0
effective	0
in	0
suppressing	0
hepatitis	3
B	4
virus	0
DNA	0
in	0
Chinese	0
hepatitis	1
B	2
surface	2
antigen	2
carriers	0
:	0
a	0
placebo	0
-	0
controlled	0
trial	0
.	0

Lamivudine	1
is	0
a	0
novel	0
2	1
'	2
,	2
3	2
'	2
-	2
dideoxy	2
cytosine	2
analogue	0
that	0
has	0
potent	0
inhibitory	0
effects	0
on	0
hepatitis	3
B	4
virus	0
replication	0
in	0
vitro	0
and	0
in	0
vivo	0
.	0

We	0
performed	0
a	0
single	0
-	0
blind	0
,	0
placebo	0
-	0
controlled	0
study	0
to	0
assess	0
its	0
effectiveness	0
and	0
safety	0
in	0
Chinese	0
hepatitis	1
B	2
surface	2
antigen	2
(	0
HBsAg	1
)	0
carriers	0
.	0

Forty	0
-	0
two	0
Chinese	0
HBsAg	1
carriers	0
were	0
randomized	0
to	0
receive	0
placebo	0
(	0
6	0
patients	0
)	0
or	0
lamivudine	1
orally	0
in	0
dosages	0
of	0
25	0
mg	0
,	0
100	0
mg	0
,	0
or	0
300	0
mg	0
daily	0
(	0
12	0
patients	0
for	0
each	0
dosage	0
)	0
.	0

The	0
drug	0
was	0
given	0
for	0
4	0
weeks	0
.	0

The	0
patients	0
were	0
closely	0
monitored	0
clinically	0
,	0
biochemically	0
,	0
and	0
serologically	0
up	0
to	0
4	0
weeks	0
after	0
drug	0
treatment	0
.	0

All	0
36	0
patients	0
receiving	0
lamivudine	1
had	0
a	0
decrease	0
in	0
hepatitis	3
B	4
virus	0
(	0
HBV	0
)	0
DNA	0
values	0
of	0
>	0
90	0
%	0
(	0
P	0
<	0
.	0
001	0
compared	0
with	0
placebo	0
)	0
.	0

Although	0
25	0
mg	0
of	0
lamivudine	1
was	0
slightly	0
less	0
effective	0
than	0
100	0
mg	0
(	0
P	0
=	0
.	0
011	0
)	0
and	0
300	0
mg	0
(	0
P	0
=	0
.	0
005	0
)	0
,	0
it	0
still	0
induced	0
94	0
%	0
suppression	0
of	0
HBV	0
DNA	0
after	0
the	0
fourth	0
week	0
of	0
therapy	0
.	0

HBV	0
DNA	0
values	0
returned	0
to	0
pretreatment	0
levels	0
within	0
4	0
weeks	0
of	0
cessation	0
of	0
therapy	0
.	0

There	0
was	0
no	0
change	0
in	0
the	0
hepatitis	3
B	4
e	0
antigen	0
status	0
or	0
in	0
aminotransferase	0
levels	0
.	0

No	0
serious	0
adverse	0
events	0
were	0
observed	0
.	0

In	0
conclusion	0
,	0
a	0
4	0
-	0
week	0
course	0
of	0
lamivudine	1
was	0
safe	0
and	0
effective	0
in	0
suppression	0
of	0
HBV	0
DNA	0
in	0
Chinese	0
HBsAg	1
carriers	0
.	0

The	0
suppression	0
was	0
>	0
90	0
%	0
but	0
reversible	0
.	0

Studies	0
with	0
long	0
-	0
term	0
lamivudine	1
administration	0
should	0
be	0
performed	0
to	0
determine	0
if	0
prolonged	0
suppression	0
of	0
HBV	0
DNA	0
can	0
be	0
achieved	0
.	0

Population	0
-	0
based	0
study	0
of	0
risk	0
of	0
venous	3
thromboembolism	4
associated	0
with	0
various	0
oral	1
contraceptives	2
.	0

BACKGR0UND	0
:	0
Four	0
studies	0
published	0
since	0
December	0
,	0
1995	0
,	0
reported	0
that	0
the	0
incidence	0
of	0
venous	3
thromboembolism	4
(	0
VTE	3
)	0
was	0
higher	0
in	0
women	0
who	0
used	0
oral	1
contraceptives	2
(	0
0Cs	1
)	0
containing	0
the	0
third	0
-	0
generation	0
progestagens	1
gestodene	1
or	0
desogestrel	1
than	0
in	0
users	0
of	0
0Cs	1
containing	0
second	0
-	0
generation	0
progestagens	1
.	0

However	0
,	0
confounding	0
and	0
bias	0
in	0
the	0
design	0
of	0
these	0
studies	0
may	0
have	0
affected	0
the	0
findings	0
.	0

The	0
aim	0
of	0
our	0
study	0
was	0
to	0
re	0
-	0
examine	0
the	0
association	0
between	0
risk	0
of	0
VTE	3
and	0
0C	1
use	0
with	0
a	0
different	0
study	0
design	0
and	0
analysis	0
to	0
avoid	0
some	0
of	0
the	0
bias	0
and	0
confounding	0
of	0
the	0
earlier	0
studies	0
.	0

METH0DS	0
:	0
We	0
used	0
computer	0
records	0
of	0
patients	0
from	0
143	0
general	0
practices	0
in	0
the	0
UK	0
.	0

The	0
study	0
was	0
based	0
on	0
the	0
medical	0
records	0
of	0
about	0
540	0
,	0
000	0
women	0
born	0
between	0
1941	0
and	0
1981	0
.	0

All	0
women	0
who	0
had	0
a	0
recorded	0
diagnosis	0
of	0
deep	3
-	4
vein	4
thrombosis	4
,	0
venous	3
thrombosis	4
not	0
otherwise	0
specified	0
,	0
or	0
pulmonary	0
embolus	0
during	0
the	0
study	0
period	0
,	0
and	0
who	0
had	0
been	0
treated	0
with	0
an	0
anticoagulant	0
were	0
identified	0
as	0
potential	0
cases	0
of	0
VTE	3
.	0

We	0
did	0
a	0
cohort	0
analysis	0
to	0
estimate	0
and	0
compare	0
incidence	0
of	0
VTE	3
in	0
users	0
of	0
the	0
main	0
0C	1
preparations	0
,	0
and	0
a	0
nested	0
case	0
-	0
control	0
study	0
to	0
calculate	0
the	0
odds	0
ratios	0
of	0
VTE	3
associated	0
with	0
use	0
of	0
different	0
types	0
of	0
0C	1
,	0
after	0
adjustment	0
for	0
potential	0
confounding	0
factors	0
.	0

In	0
the	0
case	0
-	0
control	0
study	0
,	0
we	0
matched	0
cases	0
to	0
controls	0
by	0
exact	0
year	0
of	0
birth	0
,	0
practice	0
,	0
and	0
current	0
use	0
of	0
0Cs	1
.	0

We	0
used	0
a	0
multiple	0
logistic	0
regression	0
model	0
that	0
included	0
body	0
-	0
mass	0
index	0
,	0
number	0
of	0
cycles	0
,	0
change	0
in	0
type	0
of	0
0C	1
prescribed	0
within	0
3	0
months	0
of	0
the	0
event	0
,	0
previous	0
pregnancy	0
,	0
and	0
concurrent	0
disease	0
.	0

FINDINGS	0
:	0
85	0
women	0
met	0
the	0
inclusion	0
criteria	0
for	0
VTE	3
,	0
two	0
of	0
whom	0
were	0
users	0
of	0
progestagen	1
-	0
only	0
0Cs	1
.	0

0f	0
the	0
83	0
cases	0
of	0
VTE	3
associated	0
with	0
use	0
of	0
combined	0
0Cs	1
,	0
43	0
were	0
recorded	0
as	0
deep	3
-	4
vein	4
thrombosis	4
,	0
35	0
as	0
pulmonary	0
thrombosis	3
,	0
and	0
five	0
as	0
venous	3
thrombosis	4
not	0
otherwise	0
specified	0
.	0

The	0
crude	0
rate	0
of	0
VTE	3
per	0
10	0
,	0
000	0
woman	0
-	0
years	0
was	0
4	0
.	0
10	0
in	0
current	0
users	0
of	0
any	0
0C	1
,	0
3	0
.	0
10	0
in	0
users	0
of	0
second	0
-	0
generation	0
0Cs	1
,	0
and	0
4	0
.	0
96	0
in	0
users	0
of	0
third	0
-	0
generation	0
preparations	0
.	0

After	0
adjustment	0
for	0
age	0
,	0
the	0
rate	0
ratio	0
of	0
VTE	3
in	0
users	0
of	0
third	0
-	0
generation	0
relative	0
to	0
second	0
-	0
generation	0
0Cs	1
was	0
1	0
.	0
68	0
(	0
95	0
%	0
CI	0
1	0
.	0
04	0
-	0
2	0
.	0
75	0
)	0
.	0

Logistic	0
regression	0
showed	0
no	0
significant	0
difference	0
in	0
the	0
risk	0
of	0
VTE	3
between	0
users	0
of	0
third	0
-	0
generation	0
and	0
second	0
-	0
generation	0
0Cs	1
.	0

Among	0
users	0
of	0
third	0
-	0
generation	0
progestagens	1
,	0
the	0
risk	0
of	0
VTE	3
was	0
higher	0
in	0
users	0
of	0
desogestrel	1
with	0
20	0
g	0
ethinyloestradiol	1
than	0
in	0
users	0
of	0
gestodene	1
or	0
desogestrel	1
with	0
30	0
g	0
ethinyloestradiol	1
.	0

With	0
all	0
second	0
-	0
generation	0
0Cs	1
as	0
the	0
reference	0
,	0
the	0
odds	0
ratios	0
for	0
VTE	3
were	0
3	0
.	0
49	0
(	0
1	0
.	0
21	0
-	0
10	0
.	0
12	0
)	0
for	0
desogestrel	1
plus	0
20	0
g	0
ethinyloestradiol	1
and	0
1	0
.	0
18	0
(	0
0	0
.	0
66	0
-	0
2	0
.	0
17	0
)	0
for	0
the	0
other	0
third	0
-	0
generation	0
progestagens	1
.	0

INTERPRETATI0N	0
:	0
The	0
previously	0
reported	0
increase	0
in	0
odds	0
ratio	0
associated	0
with	0
third	0
-	0
generation	0
0Cs	1
when	0
compared	0
with	0
second	0
-	0
generation	0
products	0
is	0
likely	0
to	0
have	0
been	0
the	0
result	0
of	0
residual	0
confounding	0
by	0
age	0
.	0

The	0
increased	0
odds	0
ratio	0
associated	0
with	0
products	0
containing	0
20	0
micrograms	0
ethinyloestradiol	1
and	0
desogestrel	1
compared	0
with	0
the	0
30	0
micrograms	0
product	0
is	0
biologically	0
implausible	0
,	0
and	0
is	0
likely	0
to	0
be	0
the	0
result	0
of	0
preferential	0
prescribing	0
and	0
,	0
thus	0
,	0
confounding	0
.	0

MK	1
-	2
801	2
augments	0
pilocarpine	1
-	0
induced	0
electrographic	0
seizure	3
but	0
protects	0
against	0
brain	3
damage	4
in	0
rats	0
.	0

1	0
.	0

The	0
authors	0
examined	0
the	0
anticonvulsant	0
effects	0
of	0
MK	1
-	2
801	2
on	0
the	0
pilocarpine	1
-	0
induced	0
seizure	3
model	0
.	0

Intraperitoneal	0
injection	0
of	0
pilocarpine	1
(	0
400	0
mg	0
/	0
kg	0
)	0
induced	0
tonic	3
and	4
clonic	4
seizure	4
.	0

Scopolamine	1
(	0
10	0
mg	0
/	0
kg	0
)	0
and	0
pentobarbital	1
(	0
5	0
mg	0
/	0
kg	0
)	0
prevented	0
development	0
of	0
pilocarpine	1
-	0
induced	0
behavioral	0
seizure	3
but	0
MK	1
-	2
801	2
(	0
0	0
.	0
5	0
mg	0
/	0
kg	0
)	0
did	0
not	0
.	0

2	0
.	0

An	0
electrical	0
seizure	3
measured	0
with	0
hippocampal	0
EEG	0
appeared	0
in	0
the	0
pilocarpine	1
-	0
treated	0
group	0
.	0

Scopolamine	1
and	0
pentobarbital	1
blocked	0
the	0
pilocarpine	1
-	0
induced	0
electrographic	0
seizure	3
,	0
MK	1
-	2
801	2
treatment	0
augmented	0
the	0
electrographic	0
seizure	3
induced	0
by	0
pilocarpine	1
.	0

3	0
.	0

Brain	3
damage	4
was	0
assessed	0
by	0
examining	0
the	0
hippocampus	0
microscopically	0
.	0

Pilocarpine	1
produced	0
neuronal	3
death	4
in	0
the	0
hippocampus	0
,	0
which	0
showed	0
pyknotic	0
changes	0
.	0

Pentobarbital	1
,	0
scopolamine	1
and	0
MK	1
-	2
801	2
protected	0
the	0
brain	3
damage	4
by	0
pilocarpine	1
,	0
though	0
in	0
the	0
MK	1
-	2
801	2
-	0
treated	0
group	0
,	0
the	0
pyramidal	0
cells	0
of	0
hippocampus	0
appeared	0
darker	0
than	0
normal	0
.	0

In	0
all	0
treatments	0
,	0
granule	0
cells	0
of	0
the	0
dentate	0
gyrus	0
were	0
not	0
affected	0
.	0

4	0
.	0

These	0
results	0
indicate	0
that	0
status	3
epilepticus	4
induced	0
by	0
pilocarpine	1
is	0
initiated	0
by	0
cholinergic	0
overstimulation	0
and	0
propagated	0
by	0
glutamatergic	0
transmission	0
,	0
the	0
elevation	0
of	0
which	0
may	0
cause	0
brain	3
damage	4
through	0
an	0
excitatory	0
NMDA	1
receptor	0
-	0
mediated	0
mechanism	0
.	0

Paclitaxel	1
,	0
5	1
-	2
fluorouracil	2
,	0
and	0
folinic	1
acid	2
in	0
metastatic	0
breast	3
cancer	4
:	0
BRE	0
-	0
26	0
,	0
a	0
phase	0
II	0
trial	0
.	0

5	1
-	2
Fluorouracil	2
plus	0
folinic	1
acid	2
and	0
paclitaxel	1
(	0
Taxol	1
;	0
Bristol	0
-	0
Myers	0
Squibb	0
Company	0
,	0
Princeton	0
,	0
NJ	0
)	0
are	0
effective	0
salvage	0
therapies	0
for	0
metastatic	0
breast	3
cancer	4
patients	0
.	0

Paclitaxel	1
and	0
5	1
-	2
fluorouracil	2
have	0
additive	0
cytotoxicity	3
in	0
MCF	0
-	0
7	0
cell	0
lines	0
.	0

We	0
performed	0
a	0
phase	0
II	0
trial	0
of	0
paclitaxel	1
175	0
mg	0
/	0
m2	0
over	0
3	0
hours	0
on	0
day	0
I	0
followed	0
by	0
folinic	1
acid	2
300	0
mg	0
over	0
1	0
hour	0
before	0
5	1
-	2
fluorouracil	2
350	0
mg	0
/	0
m2	0
on	0
days	0
1	0
to	0
3	0
every	0
28	0
days	0
(	0
TFL	0
)	0
in	0
women	0
with	0
metastatic	0
breast	3
cancer	4
.	0

Analysis	0
is	0
reported	0
on	0
37	0
patients	0
with	0
a	0
minimum	0
of	0
6	0
months	0
follow	0
-	0
up	0
who	0
received	0
a	0
total	0
of	0
192	0
cycles	0
of	0
TFL	0
:	0
nine	0
cycles	0
(	0
5	0
%	0
)	0
were	0
associated	0
with	0
grade	0
3	0
/	0
4	0
neutropenia	3
requiring	0
hospitalization	0
;	0
seven	0
(	0
4	0
%	0
)	0
cycles	0
in	0
two	0
patients	0
required	0
granulocyte	1
colony	2
-	2
stimulating	2
factor	2
due	0
to	0
neutropenia	3
;	0
no	0
patient	0
required	0
platelet	0
transfusions	0
.	0

Grade	0
3	0
/	0
4	0
nonhematologic	0
toxicities	3
were	0
uncommon	0
.	0

Among	0
the	0
34	0
patients	0
evaluable	0
for	0
response	0
,	0
there	0
were	0
three	0
complete	0
responses	0
(	0
9	0
%	0
)	0
and	0
18	0
partial	0
responses	0
(	0
53	0
%	0
)	0
for	0
an	0
overall	0
response	0
rate	0
of	0
62	0
%	0
.	0

0f	0
the	0
19	0
evaluable	0
patients	0
with	0
prior	0
doxorubicin	1
exposure	0
,	0
11	0
(	0
58	0
%	0
)	0
responded	0
compared	0
with	0
nine	0
of	0
15	0
(	0
60	0
%	0
)	0
without	0
prior	0
doxorubicin	1
.	0

Plasma	0
paclitaxel	1
concentrations	0
were	0
measured	0
at	0
the	0
completion	0
of	0
paclitaxel	1
infusion	0
and	0
at	0
24	0
hours	0
in	0
19	0
patients	0
.	0

TFL	0
is	0
an	0
active	0
,	0
well	0
-	0
tolerated	0
regimen	0
in	0
metastatic	0
breast	3
cancer	4
.	0

Efficacy	0
and	0
proarrhythmia	3
with	0
the	0
use	0
of	0
d	1
,	2
l	2
-	2
sotalol	2
for	0
sustained	0
ventricular	3
tachyarrhythmias	4
.	0

This	0
study	0
prospectively	0
evaluated	0
the	0
clinical	0
efficacy	0
,	0
the	0
incidence	0
of	0
torsades	3
de	4
pointes	4
,	0
and	0
the	0
presumable	0
risk	0
factors	0
for	0
torsades	3
de	4
pointes	4
in	0
patients	0
treated	0
with	0
d	1
,	2
l	2
-	2
sotalol	2
for	0
sustained	0
ventricular	3
tachyarrhythmias	4
.	0

Eighty	0
-	0
one	0
consecutive	0
patients	0
(	0
54	0
with	0
coronary	3
artery	4
disease	4
,	0
and	0
20	0
with	0
dilated	3
cardiomyopathy	4
)	0
with	0
inducible	0
sustained	0
ventricular	3
tachycardia	4
or	0
ventricular	3
fibrillation	4
received	0
oral	0
d	1
,	2
l	2
-	2
sotalol	2
to	0
prevent	0
induction	0
of	0
the	0
ventricular	3
tachyarrhythmia	4
.	0

During	0
oral	0
loading	0
with	0
d	1
,	2
l	2
-	2
sotalol	2
,	0
continuous	0
electrocardiographic	0
(	0
ECG	0
)	0
monitoring	0
was	0
performed	0
.	0

Those	0
patients	0
in	0
whom	0
d	1
,	2
l	2
-	2
sotalol	2
prevented	0
induction	0
of	0
ventricular	3
tachycardia	4
or	0
ventricular	3
fibrillation	4
were	0
discharged	0
with	0
the	0
drug	0
and	0
followed	0
up	0
on	0
an	0
outpatient	0
basis	0
for	0
21	0
+	0
/	0
-	0
18	0
months	0
.	0

Induction	0
of	0
the	0
ventricular	3
tachyarrhythmia	4
was	0
prevented	0
by	0
oral	0
d	1
,	2
l	2
-	2
sotalol	2
in	0
35	0
(	0
43	0
%	0
)	0
patients	0
;	0
the	0
ventricular	3
tachyarrhythmia	4
remained	0
inducible	0
in	0
40	0
(	0
49	0
%	0
)	0
patients	0
;	0
and	0
two	0
(	0
2	0
.	0
5	0
%	0
)	0
patients	0
did	0
not	0
tolerate	0
even	0
40	0
mg	0
of	0
d	1
,	2
l	2
-	2
sotalol	2
once	0
daily	0
.	0

Four	0
(	0
5	0
%	0
)	0
patients	0
had	0
from	0
torsades	3
de	4
pointes	4
during	0
the	0
initial	0
oral	0
treatment	0
with	0
d	1
,	2
l	2
-	2
sotalol	2
.	0

Neither	0
ECG	0
[	0
sinus	0
-	0
cycle	0
length	0
(	0
SCL	0
)	0
,	0
QT	0
or	0
QTc	0
interval	0
,	0
or	0
U	0
wave	0
]	0
nor	0
clinical	0
parameters	0
identified	0
patients	0
at	0
risk	0
for	0
torsades	3
de	4
pointes	4
.	0

However	0
,	0
the	0
oral	0
dose	0
of	0
d	1
,	2
l	2
-	2
sotalol	2
was	0
significantly	0
lower	0
in	0
patients	0
with	0
torsades	3
de	4
pointes	4
(	0
200	0
+	0
/	0
-	0
46	0
vs	0
.	0
328	0
+	0
/	0
-	0
53	0
mg	0
/	0
day	0
;	0
p	0
=	0
0	0
.	0
0017	0
)	0
.	0

Risk	0
factors	0
associated	0
with	0
the	0
development	0
of	0
torsades	3
de	4
pointes	4
were	0
the	0
appearance	0
of	0
an	0
U	0
wave	0
(	0
p	0
=	0
0	0
.	0
049	0
)	0
,	0
female	0
gender	0
(	0
p	0
=	0
0	0
.	0
015	0
)	0
,	0
and	0
significant	0
dose	0
-	0
corrected	0
changes	0
of	0
SCL	0
,	0
QT	0
interval	0
,	0
and	0
QTc	0
interval	0
(	0
p	0
<	0
0	0
.	0
05	0
)	0
.	0

During	0
follow	0
-	0
up	0
,	0
seven	0
(	0
20	0
%	0
)	0
patients	0
had	0
a	0
nonfatal	0
ventricular	3
tachycardia	4
recurrence	0
,	0
and	0
two	0
(	0
6	0
%	0
)	0
patients	0
died	0
suddenly	0
.	0

0ne	0
female	0
patient	0
with	0
stable	0
cardiac	3
disease	4
had	0
recurrent	0
torsades	3
de	4
pointes	4
after	0
2	0
years	0
of	0
successful	0
treatment	0
with	0
d	1
,	2
l	2
-	2
sotalol	2
.	0

Torsades	3
de	4
pointes	4
occurred	0
early	0
during	0
treatment	0
even	0
with	0
low	0
doses	0
of	0
oral	0
d	1
,	2
l	2
-	2
sotalol	2
.	0

Pronounced	0
changes	0
in	0
the	0
surface	0
ECG	0
(	0
cycle	0
length	0
,	0
QT	0
,	0
and	0
QTc	0
)	0
in	0
relation	0
to	0
the	0
dose	0
of	0
oral	0
d	1
,	2
l	2
-	2
sotalol	2
might	0
identify	0
a	0
subgroup	0
of	0
patients	0
with	0
an	0
increased	0
risk	0
for	0
torsades	3
de	4
pointes	4
.	0

0ther	0
ECG	0
parameters	0
before	0
the	0
application	0
of	0
d	1
,	2
l	2
-	2
sotalol	2
did	0
not	0
identify	0
patients	0
at	0
increased	0
risk	0
for	0
torsades	3
de	4
pointes	4
.	0

Recurrence	0
rates	0
of	0
ventricular	3
tachyarrhythmias	4
are	0
high	0
despite	0
complete	0
suppression	0
of	0
the	0
arrhythmia	3
during	0
programmed	0
stimulation	0
.	0

Therefore	0
programmed	0
electrical	0
stimulation	0
in	0
the	0
case	0
of	0
d	1
,	2
l	2
-	2
sotalol	2
seems	0
to	0
be	0
of	0
limited	0
prognostic	0
value	0
.	0

Chronic	0
hyperprolactinemia	3
and	0
changes	0
in	0
dopamine	1
neurons	0
.	0

The	0
tuberoinfundibular	0
dopaminergic	0
(	0
TIDA	0
)	0
system	0
is	0
known	0
to	0
inhibit	0
prolactin	0
(	0
PRL	0
)	0
secretion	0
.	0

In	0
young	0
animals	0
this	0
system	0
responds	0
to	0
acute	0
elevations	0
in	0
serum	0
PRL	0
by	0
increasing	0
its	0
activity	0
.	0

However	0
,	0
this	0
responsiveness	0
is	0
lost	0
in	0
aging	0
rats	0
with	0
chronically	0
high	0
serum	0
PRL	0
levels	0
.	0

The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
induce	0
hyperprolactinemia	3
in	0
rats	0
for	0
extended	0
periods	0
of	0
time	0
and	0
examine	0
its	0
effects	0
on	0
dopaminergic	0
systems	0
in	0
the	0
brain	0
.	0

Hyperprolactinemia	3
was	0
induced	0
by	0
treatment	0
with	0
haloperidol	1
,	0
a	0
dopamine	1
receptor	0
antagonist	0
,	0
and	0
Palkovits	0
'	0
microdissection	0
technique	0
in	0
combination	0
with	0
high	0
-	0
performance	0
liquid	0
chromatography	0
was	0
used	0
to	0
measure	0
neurotransmitter	0
concentrations	0
in	0
several	0
areas	0
of	0
the	0
brain	0
.	0

After	0
6	0
months	0
of	0
hyperprolactinemia	3
,	0
dopamine	1
(	0
DA	1
)	0
concentrations	0
in	0
the	0
median	0
eminence	0
(	0
ME	0
)	0
increased	0
by	0
84	0
%	0
over	0
the	0
control	0
group	0
.	0

Nine	0
months	0
of	0
hyperprolactinemia	3
produced	0
a	0
50	0
%	0
increase	0
in	0
DA	1
concentrations	0
in	0
the	0
ME	0
over	0
the	0
control	0
group	0
.	0

However	0
,	0
DA	1
response	0
was	0
lost	0
if	0
a	0
9	0
-	0
month	0
long	0
haloperidol	1
-	0
induced	0
hyperprolactinemia	3
was	0
followed	0
by	0
a	0
1	0
1	0
/	0
2	0
month	0
-	0
long	0
extremely	0
high	0
increase	0
in	0
serum	0
PRL	0
levels	0
produced	0
by	0
implantation	0
of	0
MMQ	0
cells	0
under	0
the	0
kidney	0
capsule	0
.	0

There	0
was	0
no	0
change	0
in	0
the	0
levels	0
of	0
DA	1
,	0
norepinephrine	1
(	0
NE	1
)	0
,	0
serotonin	1
(	0
5	1
-	2
HT	2
)	0
,	0
or	0
their	0
metabolites	0
in	0
the	0
arcuate	0
nucleus	0
(	0
AN	0
)	0
,	0
medial	0
preoptic	0
area	0
(	0
MPA	0
)	0
,	0
caudate	0
putamen	0
(	0
CP	0
)	0
,	0
substantia	0
nigra	0
(	0
SN	0
)	0
,	0
and	0
zona	0
incerta	0
(	0
ZI	0
)	0
,	0
except	0
for	0
a	0
decrease	0
in	0
5	1
-	2
hydroxyindoleacetic	2
acid	2
(	0
5	1
-	2
HIAA	2
)	0
in	0
the	0
AN	0
after	0
6	0
-	0
months	0
of	0
hyperprolactinemia	3
and	0
an	0
increase	0
in	0
DA	1
concentrations	0
in	0
the	0
AN	0
after	0
9	0
-	0
months	0
of	0
hyperprolactinemia	3
.	0

These	0
results	0
demonstrate	0
that	0
hyperprolactinemia	3
specifically	0
affects	0
TIDA	0
neurons	0
and	0
these	0
effects	0
vary	0
,	0
depending	0
on	0
the	0
duration	0
and	0
intensity	0
of	0
hyperprolactinemia	3
.	0

The	0
age	0
-	0
related	0
decrease	0
in	0
hypothalamic	0
dopamine	1
function	0
may	0
be	0
associated	0
with	0
increases	0
in	0
PRL	0
secretion	0
.	0

Treatment	0
-	0
related	0
disseminated	0
necrotizing	0
leukoencephalopathy	3
with	0
characteristic	0
contrast	0
enhancement	0
of	0
the	0
white	0
matter	0
.	0

This	0
report	0
describes	0
unique	0
contrast	0
enhancement	0
of	0
the	0
white	0
matter	0
on	0
T1	0
-	0
weighted	0
magnetic	0
resonance	0
images	0
of	0
two	0
patients	0
with	0
disseminated	0
necrotizing	0
leukoencephalopathy	3
,	0
which	0
developed	0
from	0
acute	3
lymphoblastic	4
leukemia	4
treated	0
with	0
high	0
-	0
dose	0
methotrexate	1
.	0

In	0
both	0
patients	0
,	0
the	0
enhancement	0
was	0
more	0
pronounced	0
near	0
the	0
base	0
of	0
the	0
brain	0
than	0
at	0
the	0
vertex	0
.	0

Necropsy	0
of	0
the	0
first	0
case	0
revealed	0
loss	3
of	4
myelination	4
and	0
necrosis	3
of	0
the	0
white	0
matter	0
.	0

Possible	0
mechanisms	0
causing	0
such	0
a	0
leukoencephalopathy	3
are	0
discussed	0
.	0

Thrombotic	3
complications	0
in	0
acute	3
promyelocytic	4
leukemia	4
during	0
all	1
-	2
trans	2
-	2
retinoic	2
acid	2
therapy	0
.	0

A	0
case	0
of	0
acute	3
renal	4
failure	4
,	0
due	0
to	0
occlusion	3
of	4
renal	4
vessels	4
in	0
a	0
patient	0
with	0
acute	3
promyelocytic	4
leukemia	4
(	0
APL	3
)	0
treated	0
with	0
all	1
-	2
trans	2
-	2
retinoic	2
acid	2
(	0
ATRA	1
)	0
and	0
tranexamic	1
acid	2
has	0
been	0
described	0
recently	0
.	0

We	0
report	0
a	0
case	0
of	0
acute	3
renal	4
failure	4
in	0
an	0
APL	3
patient	0
treated	0
with	0
ATRA	1
alone	0
.	0

This	0
case	0
further	0
supports	0
the	0
concern	0
about	0
thromboembolic	3
complications	0
associated	0
with	0
ATRA	1
therapy	0
in	0
APL	3
patients	0
.	0

The	0
patients	0
,	0
a	0
43	0
-	0
year	0
-	0
old	0
man	0
,	0
presented	0
all	0
the	0
signs	0
and	0
symptoms	0
of	0
APL	3
and	0
was	0
included	0
in	0
a	0
treatment	0
protocol	0
with	0
ATRA	1
.	0

After	0
10	0
days	0
of	0
treatment	0
,	0
he	0
developed	0
acute	3
renal	4
failure	4
that	0
was	0
completely	0
reversible	0
after	0
complete	0
remission	0
of	0
APL	3
was	0
achieved	0
and	0
therapy	0
discontinued	0
.	0

We	0
conclude	0
that	0
ATRA	1
is	0
a	0
valid	0
therapeutic	0
choice	0
for	0
patients	0
with	0
APL	3
,	0
although	0
the	0
procoagulant	0
tendency	0
is	0
not	0
completely	0
corrected	0
.	0

Thrombotic	3
events	0
,	0
however	0
,	0
could	0
be	0
avoided	0
by	0
using	0
low	0
-	0
dose	0
heparin	1
.	0

Pupillary	0
changes	0
associated	0
with	0
the	0
development	0
of	0
stimulant	0
-	0
induced	0
mania	3
:	0
a	0
case	0
report	0
.	0

A	0
30	0
-	0
year	0
-	0
old	0
cocaine	1
-	0
dependent	0
man	0
who	0
was	0
a	0
subject	0
in	0
a	0
study	0
evaluating	0
the	0
anticraving	0
efficacy	0
of	0
the	0
stimulant	0
medication	0
diethylpropion	1
(	0
DEP	1
)	0
became	0
manic	3
during	0
his	0
second	0
week	0
on	0
the	0
study	0
drug	0
.	0

Pupillometric	0
changes	0
while	0
on	0
DEP	1
,	0
especially	0
changes	0
in	0
the	0
total	0
power	0
of	0
pupillary	3
oscillation	4
,	0
were	0
dramatically	0
different	0
than	0
those	0
observed	0
in	0
the	0
eight	0
other	0
study	0
subjects	0
who	0
did	0
not	0
become	0
manic	3
.	0

The	0
large	0
changes	0
in	0
total	0
power	0
of	0
pupillary	3
oscillation	4
occurred	0
a	0
few	0
days	0
before	0
the	0
patient	0
became	0
fully	0
manic	3
.	0

Such	0
medication	0
-	0
associated	0
changes	0
in	0
the	0
total	0
power	0
of	0
pupillary	3
oscillation	4
might	0
be	0
of	0
utility	0
in	0
identifying	0
persons	0
at	0
risk	0
for	0
manic	3
-	0
like	0
adverse	0
effects	0
during	0
the	0
medical	0
use	0
of	0
psychomotor	0
stimulants	0
or	0
sympathomimetic	0
agents	0
.	0

Fetal	0
risks	0
due	0
to	0
warfarin	1
therapy	0
during	0
pregnancy	0
.	0

Two	0
mothers	0
with	0
heart	0
valve	0
prosthesis	0
were	0
treated	0
with	0
warfarin	1
during	0
pregnancy	0
.	0

In	0
the	0
first	0
case	0
a	0
caesarean	0
section	0
was	0
done	0
one	0
week	0
after	0
replacement	0
of	0
warfarin	1
with	0
heparin	1
.	0

The	0
baby	0
died	0
of	0
cerebral	3
and	4
pulmonary	4
hemorrhage	4
.	0

The	0
second	0
mother	0
had	0
a	0
male	0
infant	0
by	0
caesarean	0
section	0
.	0

The	0
baby	0
showed	0
warfarin	1
-	0
induced	0
embryopathy	3
with	0
nasal	3
hypoplasia	4
and	0
stippled	3
epiphyses	4
(	0
chondrodysplasia	3
punctata	4
)	0
.	0

Nasal	3
hypoplasia	4
with	0
or	0
without	0
stippled	3
epiphyses	4
has	0
now	0
been	0
reported	0
in	0
11	0
infants	0
born	0
to	0
mothers	0
treated	0
with	0
warfarin	1
during	0
the	0
first	0
trimester	0
,	0
and	0
a	0
causal	0
association	0
is	0
probable	0
.	0

In	0
view	0
of	0
the	0
risks	0
to	0
both	0
mother	0
and	0
fetus	0
in	0
women	0
with	0
prosthetic	0
cardiac	0
valves	0
it	0
is	0
recommended	0
that	0
therapeutic	0
abortion	0
be	0
advised	0
as	0
the	0
first	0
alternative	0
.	0

The	0
negative	0
mucosal	0
potential	0
:	0
separating	0
central	0
and	0
peripheral	0
effects	0
of	0
NSAIDs	0
in	0
man	0
.	0

0BJECTIVE	0
:	0
We	0
wanted	0
to	0
test	0
whether	0
assessment	0
of	0
both	0
a	0
central	0
pain	3
-	0
related	0
signal	0
(	0
chemo	0
-	0
somatosensory	0
evoked	0
potential	0
,	0
CSSEP	0
)	0
and	0
a	0
concomitantly	0
recorded	0
peripheral	0
signal	0
(	0
negative	0
mucosal	0
potential	0
,	0
NMP	0
)	0
allows	0
for	0
separation	0
of	0
central	0
and	0
peripheral	0
effects	0
of	0
NSAIDs	0
.	0

For	0
this	0
purpose	0
,	0
experimental	0
conditions	0
were	0
created	0
in	0
which	0
NSAIDs	0
had	0
previously	0
been	0
observed	0
to	0
produce	0
effects	0
on	0
phasic	0
and	0
tonic	0
pain	3
by	0
either	0
central	0
or	0
peripheral	0
mechanisms	0
.	0

METH0DS	0
:	0
According	0
to	0
a	0
double	0
-	0
blind	0
,	0
randomised	0
,	0
controlled	0
,	0
threefold	0
cross	0
-	0
over	0
design	0
,	0
18	0
healthy	0
subjects	0
(	0
11	0
males	0
,	0
7	0
females	0
;	0
mean	0
age	0
26	0
years	0
)	0
received	0
either	0
placebo	0
,	0
400	0
mg	0
ibuprofen	1
,	0
or	0
800	0
mg	0
ibuprofen	1
.	0

Phasic	0
pain	3
was	0
applied	0
by	0
means	0
of	0
short	0
pulses	0
of	0
C02	1
to	0
the	0
nasal	0
mucosa	0
(	0
stimulus	0
duration	0
500	0
ms	0
,	0
interval	0
approximately	0
60	0
s	0
)	0
,	0
and	0
tonic	0
pain	3
was	0
induced	0
in	0
the	0
nasal	0
cavity	0
by	0
means	0
of	0
dry	0
air	0
of	0
controlled	0
temperature	0
,	0
humidity	0
and	0
flow	0
rate	0
(	0
22	0
degrees	0
C	0
,	0
0	0
%	0
relative	0
humidity	0
,	0
145	0
ml	0
.	0
s	0
-	0
1	0
)	0
.	0

Both	0
CSSEPs	0
as	0
central	0
and	0
NMPs	0
as	0
peripheral	0
correlates	0
of	0
pain	3
were	0
obtained	0
in	0
response	0
to	0
the	0
C02	1
stimuli	0
.	0

Additionally	0
,	0
the	0
subjects	0
rated	0
the	0
intensity	0
of	0
both	0
phasic	0
and	0
tonic	0
pain	3
by	0
means	0
of	0
visual	0
analogue	0
scales	0
.	0

RESULTS	0
:	0
As	0
described	0
earlier	0
,	0
administration	0
of	0
ibuprofen	1
was	0
followed	0
by	0
a	0
decrease	0
in	0
tonic	0
pain	3
but	0
-	0
relative	0
to	0
placebo	0
-	0
an	0
increase	0
in	0
correlates	0
of	0
phasic	0
pain	3
,	0
indicating	0
a	0
specific	0
effect	0
of	0
ibuprofen	1
on	0
the	0
interaction	0
between	0
the	0
pain	3
stimuli	0
under	0
these	0
special	0
experimental	0
conditions	0
.	0

Based	0
on	0
the	0
similar	0
behaviour	0
of	0
CSSEP	0
and	0
NMP	0
,	0
it	0
was	0
concluded	0
that	0
the	0
pharmacological	0
process	0
underlying	0
this	0
phenomenon	0
was	0
localised	0
in	0
the	0
periphery	0
.	0

By	0
means	0
of	0
the	0
simultaneous	0
recording	0
of	0
interrelated	0
peripheral	0
and	0
central	0
electrophysiologic	0
correlates	0
of	0
nociception	0
,	0
it	0
was	0
possible	0
to	0
separate	0
central	0
and	0
peripheral	0
effects	0
of	0
an	0
NSAID	0
.	0

The	0
major	0
advantage	0
of	0
this	0
pain	3
model	0
is	0
the	0
possibility	0
of	0
obtaining	0
peripheral	0
pain	3
-	0
related	0
activity	0
directly	0
using	0
a	0
non	0
-	0
invasive	0
technique	0
in	0
humans	0
.	0

Effect	0
of	0
D	1
-	2
Glucarates	2
on	0
basic	0
antibiotic	0
-	0
induced	0
renal	3
damage	4
in	0
rats	0
.	0

Dehydrated	3
rats	0
regularly	0
develop	0
acute	3
renal	4
failure	4
following	0
single	0
injection	0
of	0
aminoglycoside	1
antibiotics	0
combined	0
with	0
dextran	0
or	0
of	0
antibiotics	0
only	0
.	0

0ral	0
administration	0
of	0
2	1
,	2
5	2
-	2
di	2
-	2
0	2
-	2
acetyl	2
-	2
D	2
-	2
glucaro	2
-	2
1	2
,	2
4	2
-	2
6	2
,	2
3	2
-	2
dilactone	2
protected	0
rats	0
against	0
renal	3
failure	4
induced	0
by	0
kanamycin	1
-	0
dextran	0
.	0

The	0
protective	0
effect	0
was	0
prevalent	0
among	0
D	1
-	2
glucarates	2
,	0
and	0
also	0
to	0
other	0
saccharic	1
acid	2
,	0
hexauronic	1
acids	2
and	0
hexaaldonic	1
acids	2
,	0
although	0
to	0
a	0
lesser	0
degree	0
,	0
but	0
not	0
to	0
a	0
hexaaldose	0
,	0
sugar	1
alcohols	2
,	0
substances	0
inthe	0
TCA	1
cycle	0
and	0
other	0
acidic	0
compounds	0
.	0

D	1
-	2
Glucarates	2
were	0
effective	0
against	0
renal	3
damage	4
induced	0
by	0
peptide	0
antibiotics	0
as	0
well	0
as	0
various	0
aminoglycoside	1
antibitocis	0
.	0

Dose	0
-	0
responses	0
were	0
observed	0
in	0
the	0
protective	0
effect	0
of	0
D	1
-	2
Glucarates	2
.	0

With	0
a	0
D	1
-	2
glucarate	2
of	0
a	0
fixed	0
size	0
of	0
dose	0
,	0
approximately	0
the	0
same	0
degree	0
of	0
protection	0
was	0
obtained	0
against	0
renal	3
damages	4
induced	0
by	0
different	0
basic	0
antibiotics	0
despite	0
large	0
disparities	0
in	0
administration	0
doses	0
of	0
different	0
antibiotics	0
.	0

D	1
-	2
Glucarates	2
had	0
the	0
ability	0
to	0
prevent	0
renal	3
damage	4
but	0
not	0
to	0
cure	0
it	0
.	0

Rats	0
excreted	0
acidic	0
urine	0
when	0
they	0
were	0
spared	0
from	0
renal	3
lesions	4
by	0
monosaccharides	1
.	0

The	0
reduction	0
effect	0
of	0
D	1
-	2
glucarates	2
against	0
nephrotoxicity	3
of	0
basic	0
antibiotics	0
was	0
discussed	0
.	0

Acute	0
severe	0
depression	3
following	0
peri	0
-	0
operative	0
ondansetron	1
.	0

A	0
41	0
-	0
year	0
-	0
old	0
woman	0
with	0
a	0
strong	0
history	0
of	0
postoperative	3
nausea	4
and	4
vomiting	4
presented	0
for	0
abdominal	0
hysterectomy	0
3	0
months	0
after	0
a	0
previous	0
anaesthetic	0
where	0
ondansetron	1
prophylaxis	0
had	0
been	0
used	0
.	0

She	0
had	0
developed	0
a	0
severe	0
acute	0
major	3
depression	4
disorder	4
almost	0
immediately	0
thereafter	0
,	0
possibly	0
related	0
to	0
the	0
use	0
of	0
a	0
serotonin	1
antagonist	0
.	0

Nine	0
years	0
before	0
she	0
had	0
experienced	0
a	0
self	0
-	0
limited	0
puerperal	0
depressive	3
episode	4
.	0

Anaesthesia	0
with	0
a	0
propofol	1
infusion	0
and	0
avoidance	0
of	0
serotonin	1
antagonists	0
provided	0
a	0
nausea	3
-	0
free	0
postoperative	0
course	0
without	0
exacerbation	0
of	0
the	0
depression	3
disorder	4
.	0

Hypertensive	3
response	0
during	0
dobutamine	1
stress	0
echocardiography	0
.	0

Among	0
3	0
,	0
129	0
dobutamine	1
stress	0
echocardiographic	0
studies	0
,	0
a	0
hypertensive	3
response	0
,	0
defined	0
as	0
systolic	0
blood	0
pressure	0
(	0
BP	0
)	0
>	0
or	0
=	0
220	0
mm	0
Hg	0
and	0
/	0
or	0
diastolic	0
BP	0
>	0
or	0
=	0
110	0
mm	0
Hg	0
,	0
occurred	0
in	0
30	0
patients	0
(	0
1	0
%	0
)	0
.	0

Patients	0
with	0
this	0
response	0
more	0
often	0
had	0
a	0
history	0
of	0
hypertension	3
and	0
had	0
higher	0
resting	0
systolic	0
and	0
diastolic	0
BP	0
before	0
dobutamine	1
infusion	0
.	0

Continuously	0
nebulized	0
albuterol	1
in	0
severe	0
exacerbations	0
of	0
asthma	3
in	0
adults	0
:	0
a	0
case	0
-	0
controlled	0
study	0
.	0

A	0
retrospective	0
,	0
case	0
-	0
controlled	0
analysis	0
comparing	0
patients	0
admitted	0
to	0
a	0
medical	0
intensive	0
care	0
unit	0
with	0
severe	0
exacerbations	0
of	0
asthma	3
who	0
received	0
continuously	0
nebulized	0
albuterol	1
(	0
CNA	0
)	0
versus	0
intermittent	0
albuterol	1
(	0
INA	0
)	0
treatments	0
is	0
reported	0
.	0

Forty	0
matched	0
pairs	0
of	0
patients	0
with	0
asthma	3
are	0
compared	0
.	0

CNA	0
was	0
administered	0
for	0
a	0
mean	0
of	0
11	0
+	0
/	0
-	0
10	0
hr	0
.	0

The	0
incidence	0
of	0
cardiac	3
dysrhythmias	4
was	0
similar	0
between	0
groups	0
.	0

Symptomatic	0
hypokalemia	3
did	0
not	0
occur	0
.	0

CNA	0
patients	0
had	0
higher	0
heart	0
rates	0
during	0
treatment	0
,	0
which	0
may	0
reflect	0
severity	0
of	0
illness	0
.	0

The	0
incidence	0
of	0
intubation	0
was	0
similar	0
.	0

We	0
conclude	0
that	0
CNA	0
and	0
INA	0
demonstrated	0
similar	0
profiles	0
with	0
regard	0
to	0
safety	0
,	0
morbidity	0
,	0
and	0
mortality	0
.	0

Paraplegia	3
following	0
intrathecal	0
methotrexate	1
:	0
report	0
of	0
a	0
case	0
and	0
review	0
of	0
the	0
literature	0
.	0

A	0
patient	0
who	0
developed	0
paraplegia	3
following	0
the	0
intrathecal	0
instillation	0
of	0
methotrexate	1
is	0
discribed	0
.	0

The	0
ten	0
previously	0
reported	0
cases	0
of	0
this	0
unusual	0
complication	0
are	0
reviewed	0
.	0

The	0
following	0
factors	0
appear	0
to	0
predispose	0
to	0
the	0
development	0
of	0
this	0
complication	0
:	0
abnormal	0
cerebrospinal	0
dynamics	0
related	0
to	0
the	0
presence	0
of	0
central	3
nervous	4
system	4
leukemia	4
,	0
and	0
epidural	0
cerebrospinal	0
leakage	0
;	0
elevated	0
cerebrospinal	0
fluid	0
methothexate	1
concentration	0
related	0
to	0
abnormal	0
cerebrospinal	0
fluid	0
dynamics	0
and	0
to	0
inappropriately	0
high	0
methotrexate	1
doses	0
based	0
on	0
body	0
surface	0
area	0
calculations	0
in	0
older	0
children	0
and	0
adults	0
;	0
the	0
presence	0
of	0
neurotoxic	3
preservatives	0
in	0
commercially	0
available	0
methotrexate	1
preparations	0
and	0
diluents	0
;	0
and	0
the	0
use	0
of	0
methotrexate	1
diluents	0
of	0
unphysiologic	0
pH	0
,	0
ionic	0
content	0
and	0
osmolarity	0
.	0

The	0
role	0
of	0
methotrexate	1
contaminants	0
,	0
local	0
folate	3
deficiency	4
,	0
and	0
cranial	0
irradiation	0
in	0
the	0
pathogenesis	0
of	0
intrathecal	0
methotrexate	1
toxicity	3
is	0
unclear	0
.	0

The	0
incidence	0
of	0
neurotoxicity	3
may	0
be	0
reduced	0
by	0
employing	0
lower	0
doses	0
of	0
methotrexate	1
in	0
the	0
presence	0
of	0
central	3
nervous	4
system	4
leukemia	4
,	0
in	0
older	0
children	0
and	0
adults	0
,	0
and	0
in	0
the	0
presence	0
of	0
epidural	0
leakage	0
.	0

0nly	0
preservative	0
-	0
free	0
methotrexate	1
in	0
Elliott	0
'	0
s	0
B	0
Solution	0
at	0
a	0
concentration	0
of	0
not	0
more	0
than	0
1	0
mg	0
/	0
ml	0
should	0
be	0
used	0
for	0
intrathecal	0
administration	0
.	0

Periodic	0
monitoring	0
of	0
cerebruspinal	0
fluid	0
methotrexate	1
levels	0
may	0
be	0
predictive	0
of	0
the	0
development	0
of	0
serious	0
neurotoxicity	3
.	0

Hyperosmolar	3
nonketotic	4
coma	4
precipitated	0
by	0
lithium	1
-	0
induced	0
nephrogenic	3
diabetes	4
insipidus	4
.	0

A	0
45	0
-	0
year	0
-	0
old	0
man	0
,	0
with	0
a	0
10	0
-	0
year	0
history	0
of	0
manic	3
depression	4
treated	0
with	0
lithium	1
,	0
was	0
admitted	0
with	0
hyperosmolar	3
,	4
nonketotic	4
coma	4
.	0

He	0
gave	0
a	0
five	0
-	0
year	0
history	0
of	0
polyuria	3
and	0
polydipsia	3
,	0
during	0
which	0
time	0
urinalysis	0
had	0
been	0
negative	0
for	0
glucose	1
.	0

After	0
recovery	0
from	0
hyperglycaemia	3
,	0
he	0
remained	0
polyuric	3
despite	0
normal	0
blood	0
glucose	1
concentrations	0
;	0
water	0
deprivation	0
testing	0
indicated	0
nephrogenic	3
diabetes	4
insipidus	4
,	0
likely	0
to	0
be	0
lithium	1
-	0
induced	0
.	0

We	0
hypothesize	0
that	0
when	0
this	0
man	0
developed	0
type	3
2	4
diabetes	4
,	0
chronic	0
polyuria	3
due	0
to	0
nephrogenic	3
diabetes	4
insipidus	4
was	0
sufficient	0
to	0
precipitate	0
hyperosmolar	0
dehydration	3
.	0

Effects	0
of	0
the	0
intracoronary	0
infusion	0
of	0
cocaine	1
on	0
left	0
ventricular	0
systolic	0
and	0
diastolic	0
function	0
in	0
humans	0
.	0

BACKGR0UND	0
:	0
In	0
dogs	0
,	0
a	0
large	0
amount	0
of	0
intravenous	0
cocaine	1
causes	0
a	0
profound	0
deterioration	3
of	4
left	4
ventricular	4
(	4
LV	4
)	4
systolic	4
function	4
and	0
an	0
increase	0
in	0
LV	0
end	0
-	0
diastolic	0
pressure	0
.	0

This	0
study	0
was	0
done	0
to	0
assess	0
the	0
influence	0
of	0
a	0
high	0
intracoronary	0
cocaine	1
concentration	0
on	0
LV	0
systolic	0
and	0
diastolic	0
function	0
in	0
humans	0
.	0

METH0DS	0
AND	0
RESULTS	0
:	0
In	0
20	0
patients	0
(	0
14	0
men	0
and	0
6	0
women	0
aged	0
39	0
to	0
72	0
years	0
)	0
referred	0
for	0
cardiac	0
catheterization	0
for	0
the	0
evaluation	0
of	0
chest	3
pain	4
,	0
we	0
measured	0
heart	0
rate	0
,	0
systemic	0
arterial	0
pressure	0
,	0
LV	0
pressure	0
and	0
its	0
first	0
derivative	0
(	0
dP	0
/	0
dt	0
)	0
,	0
and	0
LV	0
volumes	0
and	0
ejection	0
fraction	0
before	0
and	0
during	0
the	0
final	0
2	0
to	0
3	0
minutes	0
of	0
a	0
15	0
-	0
minute	0
intracoronary	0
infusion	0
of	0
saline	0
(	0
n	0
=	0
10	0
,	0
control	0
subjects	0
)	0
or	0
cocaine	1
hydrochloride	2
1	0
mg	0
/	0
min	0
(	0
n	0
=	0
10	0
)	0
.	0

No	0
variable	0
changed	0
with	0
saline	0
.	0

With	0
cocaine	1
,	0
the	0
drug	0
concentration	0
in	0
blood	0
obtained	0
from	0
the	0
coronary	0
sinus	0
was	0
3	0
.	0
0	0
+	0
/	0
-	0
0	0
.	0
4	0
(	0
mean	0
+	0
/	0
-	0
SD	0
)	0
mg	0
/	0
L	0
,	0
similar	0
in	0
magnitude	0
to	0
the	0
blood	0
cocaine	1
concentration	0
reported	0
in	0
abusers	0
dying	0
of	0
cocaine	1
intoxication	0
.	0

Cocaine	1
induced	0
no	0
significant	0
change	0
in	0
heart	0
rate	0
,	0
LV	0
dP	0
/	0
dt	0
(	0
positive	0
or	0
negative	0
)	0
,	0
or	0
LV	0
end	0
-	0
diastolic	0
volume	0
,	0
but	0
it	0
caused	0
an	0
increase	0
in	0
systolic	0
and	0
mean	0
arterial	0
pressures	0
,	0
LV	0
end	0
-	0
diastolic	0
pressure	0
,	0
and	0
LV	0
end	0
-	0
systolic	0
volume	0
,	0
as	0
well	0
as	0
a	0
decrease	0
in	0
LV	0
ejection	0
fraction	0
.	0

C0NCLUSI0NS	0
:	0
In	0
humans	0
,	0
the	0
intracoronary	0
infusion	0
of	0
cocaine	1
sufficient	0
in	0
amount	0
to	0
achieve	0
a	0
high	0
drug	0
concentration	0
in	0
coronary	0
sinus	0
blood	0
causes	0
a	0
deterioration	3
of	4
LV	4
systolic	4
and	4
diastolic	4
performance	4
.	0

Ascending	0
dose	0
tolerance	0
study	0
of	0
intramuscular	0
carbetocin	1
administered	0
after	0
normal	0
vaginal	0
birth	0
.	0

0BJECTIVE	0
:	0
To	0
determine	0
the	0
maximum	0
tolerated	0
dose	0
(	0
MTD	0
)	0
of	0
carbetocin	1
(	0
a	0
long	0
-	0
acting	0
synthetic	0
analogue	0
of	0
oxytocin	1
)	0
,	0
when	0
administered	0
immediately	0
after	0
vaginal	0
delivery	0
at	0
term	0
.	0

MATERIALS	0
AND	0
METH0DS	0
:	0
Carbetocin	1
was	0
given	0
as	0
an	0
intramuscular	0
injection	0
immediately	0
after	0
the	0
birth	0
of	0
the	0
infant	0
in	0
45	0
healthy	0
women	0
with	0
normal	0
singleton	0
pregnancies	0
who	0
delivered	0
vaginally	0
at	0
term	0
.	0

Dosage	0
groups	0
of	0
15	0
,	0
30	0
,	0
50	0
,	0
75	0
,	0
100	0
,	0
125	0
,	0
150	0
,	0
175	0
or	0
200	0
microg	0
carbetocin	1
were	0
assigned	0
to	0
blocks	0
of	0
three	0
women	0
according	0
to	0
the	0
continual	0
reassessment	0
method	0
(	0
CRM	0
)	0
.	0

RESULTS	0
:	0
All	0
dosage	0
groups	0
consisted	0
of	0
three	0
women	0
,	0
except	0
those	0
with	0
100	0
microg	0
(	0
n	0
=	0
6	0
)	0
and	0
200	0
microg	0
(	0
n	0
=	0
18	0
)	0
.	0

Recorded	0
were	0
dose	0
-	0
limiting	0
adverse	0
events	0
:	0
hyper	3
-	4
or	4
hypotension	4
(	0
three	0
)	0
,	0
severe	0
abdominal	3
pain	4
(	0
0	0
)	0
,	0
vomiting	3
(	0
0	0
)	0
and	0
retained	3
placenta	4
(	0
four	0
)	0
.	0

Serious	0
adverse	0
events	0
occurred	0
in	0
seven	0
women	0
:	0
six	0
cases	0
with	0
blood	3
loss	4
>	0
or	0
=	0
1000	0
ml	0
,	0
four	0
cases	0
of	0
manual	0
placenta	0
removal	0
,	0
five	0
cases	0
of	0
additional	0
oxytocics	0
administration	0
and	0
five	0
cases	0
of	0
blood	0
transfusion	0
.	0

Maximum	0
blood	3
loss	4
was	0
greatest	0
at	0
the	0
upper	0
and	0
lower	0
dose	0
levels	0
,	0
and	0
lowest	0
in	0
the	0
70	0
-	0
125	0
microg	0
dose	0
range	0
.	0

Four	0
out	0
of	0
six	0
cases	0
with	0
blood	3
loss	4
>	0
or	0
=	0
1000	0
ml	0
occurred	0
in	0
the	0
200	0
microg	0
group	0
.	0

The	0
majority	0
of	0
additional	0
administration	0
of	0
oxytocics	0
(	0
4	0
/	0
5	0
)	0
and	0
blood	0
transfusion	0
(	0
3	0
/	0
5	0
)	0
occurred	0
in	0
the	0
dose	0
groups	0
of	0
200	0
microg	0
.	0

All	0
retained	0
placentae	0
were	0
found	0
in	0
the	0
group	0
of	0
200	0
microg	0
.	0

C0NCLUSI0N	0
:	0
The	0
MTD	0
was	0
calculated	0
to	0
be	0
at	0
200	0
microg	0
carbetocin	1
.	0

Heparin	1
-	0
induced	0
thrombocytopenia	3
,	0
paradoxical	0
thromboembolism	3
,	0
and	0
other	0
side	0
effects	0
of	0
heparin	1
therapy	0
.	0

Although	0
several	0
new	0
anticoagulant	0
drugs	0
are	0
in	0
development	0
,	0
heparin	1
remains	0
the	0
drug	0
of	0
choice	0
for	0
most	0
anticoagulation	0
needs	0
.	0

The	0
clinical	0
effects	0
of	0
heparin	1
are	0
meritorious	0
,	0
but	0
side	0
effects	0
do	0
exist	0
.	0

Important	0
untoward	0
effects	0
of	0
heparin	1
therapy	0
including	0
heparin	1
-	0
induced	0
thrombocytopenia	3
,	0
heparin	1
-	0
associated	0
osteoporosis	3
,	0
eosinophilia	3
,	0
skin	3
reactions	4
,	0
allergic	3
reactions	4
other	0
than	0
thrombocytopenia	3
and	0
alopecia	3
will	0
be	0
discussed	0
in	0
this	0
article	0
.	0

Nonopaque	0
crystal	0
deposition	0
causing	0
ureteric	3
obstruction	4
in	0
patients	0
with	0
HIV	0
undergoing	0
indinavir	1
therapy	0
.	0

0BJECTIVE	0
:	0
We	0
describe	0
the	0
unique	0
CT	0
features	0
of	0
ureteric	3
calculi	4
in	0
six	0
HIV	3
-	4
infected	4
patients	0
receiving	0
indinavir	1
,	0
the	0
most	0
commonly	0
used	0
HIV	0
protease	0
inhibitor	0
,	0
which	0
is	0
associated	0
with	0
an	0
increased	0
incidence	0
of	0
urolithiasis	3
.	0

C0NCLUSI0N	0
:	0
Ureteric	3
obstruction	4
caused	0
by	0
precipitated	0
indinavir	1
crystals	0
may	0
be	0
difficult	0
to	0
diagnose	0
with	0
unenhanced	0
CT	0
.	0

The	0
calculi	0
are	0
not	0
opaque	0
,	0
and	0
secondary	0
signs	0
of	0
obstruction	0
may	0
be	0
absent	0
or	0
minimal	0
and	0
should	0
be	0
sought	0
carefully	0
.	0

Images	0
may	0
need	0
to	0
be	0
obtained	0
using	0
i	0
.	0
v	0
.	0
contrast	0
material	0
to	0
enable	0
diagnosis	0
of	0
ureteric	3
stones	4
or	4
obstruction	4
in	0
patients	0
with	0
HIV	3
infection	4
who	0
receive	0
indinavir	1
therapy	0
.	0

Ischemic	3
colitis	4
and	0
sumatriptan	1
use	0
.	0

Sumatriptan	1
succinate	2
,	0
a	0
serotonin	1
-	0
1	0
(	0
5	1
-	2
hydroxytryptamine	2
-	0
1	0
)	0
receptor	0
agonist	0
,	0
is	0
an	0
antimigraine	0
drug	0
that	0
is	0
reported	0
to	0
act	0
by	0
selectively	0
constricting	0
intracranial	0
arteries	0
.	0

Recently	0
,	0
vasopressor	0
responses	0
that	0
are	0
distinct	0
from	0
the	0
cranial	0
circulation	0
have	0
been	0
demonstrated	0
to	0
occur	0
in	0
the	0
systemic	0
,	0
pulmonary	0
,	0
and	0
coronary	0
circulations	0
.	0

Cases	0
have	0
been	0
published	0
of	0
coronary	3
vasospasm	4
,	0
myocardial	3
ischemia	4
,	0
and	0
myocardial	3
infarction	4
occurring	0
after	0
sumatriptan	1
use	0
.	0

We	0
report	0
on	0
the	0
development	0
of	0
8	0
serious	0
cases	0
of	0
ischemic	3
colitis	4
in	0
patients	0
with	0
migraine	3
treated	0
with	0
sumatriptan	1
.	0

Pallidotomy	0
with	0
the	0
gamma	0
knife	0
:	0
a	0
positive	0
experience	0
.	0

51	0
patients	0
with	0
medically	0
refractory	0
Parkinson	3
'	4
s	4
disease	4
underwent	0
stereotactic	0
posteromedial	0
pallidotomy	0
between	0
August	0
1993	0
and	0
February	0
1997	0
for	0
treatment	0
of	0
bradykinesia	3
,	0
rigidity	3
,	0
and	0
L	1
-	2
D0PA	2
-	0
induced	0
dyskinesias	3
.	0

In	0
29	0
patients	0
,	0
the	0
pallidotomies	0
were	0
performed	0
with	0
the	0
Leksell	0
Gamma	0
Knife	0
and	0
in	0
22	0
they	0
were	0
performed	0
with	0
the	0
standard	0
radiofrequency	0
(	0
RF	0
)	0
method	0
.	0

Clinical	0
assessment	0
as	0
well	0
as	0
blinded	0
ratings	0
of	0
Unified	0
Parkinson	3
'	4
s	4
Disease	4
Rating	0
Scale	0
(	0
UPDRS	0
)	0
scores	0
were	0
carried	0
out	0
pre	0
-	0
and	0
postoperatively	0
.	0

Mean	0
follow	0
-	0
up	0
time	0
is	0
20	0
.	0
6	0
months	0
(	0
range	0
6	0
-	0
48	0
)	0
and	0
all	0
except	0
4	0
patients	0
have	0
been	0
followed	0
more	0
than	0
one	0
year	0
.	0

85	0
percent	0
of	0
patients	0
with	0
dyskinesias	3
were	0
relieved	0
of	0
symptoms	0
,	0
regardless	0
of	0
whether	0
the	0
pallidotomies	0
were	0
performed	0
with	0
the	0
Gamma	0
Knife	0
or	0
radiofrequency	0
methods	0
.	0

About	0
2	0
/	0
3	0
of	0
the	0
patients	0
in	0
both	0
Gamma	0
Knife	0
and	0
radiofrequency	0
groups	0
showed	0
improvements	0
in	0
bradykinesia	3
and	0
rigidity	3
,	0
although	0
when	0
considered	0
as	0
a	0
group	0
neither	0
the	0
Gamma	0
Knife	0
nor	0
the	0
radiofrequency	0
group	0
showed	0
statistically	0
significant	0
improvements	0
in	0
UPDRS	0
scores	0
.	0

0ne	0
patient	0
in	0
the	0
Gamma	0
Knife	0
group	0
(	0
3	0
.	0
4	0
%	0
)	0
developed	0
a	0
homonymous	3
hemianopsia	4
9	0
months	0
following	0
treatment	0
and	0
5	0
patients	0
(	0
27	0
.	0
7	0
%	0
)	0
in	0
the	0
radiofrequency	0
group	0
became	0
transiently	0
confused	0
postoperatively	0
.	0

No	0
other	0
complications	0
were	0
seen	0
.	0

Gamma	0
Knife	0
pallidotomy	0
is	0
as	0
effective	0
as	0
radiofrequency	0
pallidotomy	0
in	0
controlling	0
certain	0
of	0
the	0
symptoms	0
of	0
Parkinson	3
'	4
s	4
disease	4
.	0

It	0
may	0
be	0
the	0
only	0
practical	0
technique	0
available	0
in	0
certain	0
patients	0
,	0
such	0
as	0
those	0
who	0
take	0
anticoagulants	0
,	0
have	0
bleeding	3
diatheses	0
or	0
serious	0
systemic	0
medical	0
illnesses	0
.	0

It	0
is	0
a	0
viable	0
option	0
for	0
other	0
patients	0
as	0
well	0
.	0

Centrally	0
mediated	0
cardiovascular	0
effects	0
of	0
intracisternal	0
application	0
of	0
carbachol	1
in	0
anesthetized	0
rats	0
.	0

The	0
pressor	0
response	0
to	0
the	0
intracisternal	0
(	0
i	0
.	0
c	0
.	0
)	0
injection	0
of	0
carbachol	1
(	0
1	0
mug	0
)	0
in	0
anesthetized	0
rats	0
was	0
analyzed	0
.	0

This	0
response	0
was	0
significantly	0
reduced	0
by	0
the	0
intravenous	0
(	0
i	0
.	0
v	0
.	0
)	0
injection	0
of	0
guanethidine	1
(	0
5	0
mg	0
)	0
,	0
hexamethonium	1
(	0
10	0
mg	0
)	0
or	0
phentolamine	1
(	0
5	0
mg	0
)	0
,	0
and	0
conversely	0
,	0
potentiated	0
by	0
i	0
.	0
v	0
.	0
desmethylimipramine	1
(	0
0	0
.	0
3	0
mg	0
)	0
,	0
while	0
propranolol	1
(	0
0	0
.	0
5	0
mg	0
)	0
i	0
.	0
v	0
.	0
selectively	0
inhibited	0
the	0
enlargement	3
of	4
pulse	4
pressure	4
and	0
the	0
tachycardia	3
following	0
i	0
.	0
c	0
.	0
carbachol	1
(	0
1	0
mug	0
)	0
.	0

0n	0
the	0
other	0
hand	0
,	0
the	0
pressor	0
response	0
to	0
i	0
.	0
c	0
.	0
carbachol	1
(	0
1	0
mug	0
)	0
was	0
almost	0
completely	0
blocked	0
by	0
i	0
.	0
c	0
.	0
atropine	1
(	0
3	0
mug	0
)	0
or	0
hexamethonium	1
(	0
500	0
mug	0
)	0
,	0
and	0
significantly	0
reduced	0
by	0
i	0
.	0
c	0
.	0
chlorpromazine	1
(	0
50	0
mug	0
)	0
but	0
significantly	0
potentiated	0
by	0
i	0
.	0
c	0
.	0
desmethylimipramine	1
(	0
30	0
mug	0
)	0
.	0

The	0
pressor	0
response	0
to	0
i	0
.	0
c	0
.	0
carbachol	1
(	0
1	0
mug	0
)	0
remained	0
unchanged	0
after	0
sectioning	0
of	0
the	0
bilateral	0
cervical	0
vagal	0
nerves	0
but	0
disappeared	0
after	0
sectioning	0
of	0
the	0
spinal	0
cord	0
(	0
C7	0
-	0
C8	0
)	0
.	0

From	0
the	0
above	0
result	0
it	0
is	0
suggested	0
that	0
the	0
pressor	0
response	0
to	0
i	0
.	0
c	0
.	0
carbachol	1
ortral	0
and	0
peripheral	0
adrenergic	0
mechanisms	0
,	0
and	0
that	0
the	0
sympathetic	0
trunk	0
is	0
the	0
main	0
pathway	0
.	0

Neuroleptic	3
malignant	4
syndrome	4
and	0
methylphenidate	1
.	0

A	0
1	0
-	0
year	0
-	0
old	0
female	0
presented	0
with	0
neuroleptic	3
malignant	4
syndrome	4
probably	0
caused	0
by	0
methylphenidate	1
.	0

She	0
had	0
defects	0
in	0
the	0
supratentorial	0
brain	0
including	0
the	0
basal	0
ganglia	0
and	0
the	0
striatum	0
(	0
multicystic	3
encephalomalacia	4
)	0
due	0
to	0
severe	0
perinatal	0
hypoxic	3
-	4
ischemic	4
encephalopathy	4
,	0
which	0
was	0
considered	0
to	0
be	0
a	0
possible	0
predisposing	0
factor	0
causing	0
neuroleptic	3
malignant	4
syndrome	4
.	0

A	0
dopaminergic	0
blockade	0
mechanism	0
generally	0
is	0
accepted	0
as	0
the	0
pathogenesis	0
of	0
this	0
syndrome	0
.	0

However	0
,	0
methylphenidate	1
is	0
a	0
dopamine	1
agonist	0
via	0
the	0
inhibition	0
of	0
uptake	0
of	0
dopamine	1
,	0
and	0
therefore	0
dopaminergic	0
systems	0
in	0
the	0
brainstem	0
(	0
mainly	0
the	0
midbrain	0
)	0
and	0
the	0
spinal	0
cord	0
were	0
unlikely	0
to	0
participate	0
in	0
the	0
onset	0
of	0
this	0
syndrome	0
.	0

A	0
relative	0
gamma	1
-	2
aminobutyric	2
acid	2
-	0
ergic	0
deficiency	0
might	0
occur	0
because	0
diazepam	1
,	0
a	0
gamma	1
-	2
aminobutyric	2
acid	2
-	0
mimetic	0
agent	0
,	0
was	0
strikingly	0
effective	0
.	0

This	0
is	0
the	0
first	0
reported	0
patient	0
with	0
neuroleptic	3
malignant	4
syndrome	4
probably	0
caused	0
by	0
methylphenidate	1
.	0

Differential	0
effects	0
of	0
17alpha	1
-	2
ethinylestradiol	2
on	0
the	0
neutral	0
and	0
acidic	0
pathways	0
of	0
bile	1
salt	2
synthesis	0
in	0
the	0
rat	0
.	0

Effects	0
of	0
17alpha	1
-	2
ethinylestradiol	2
(	0
EE	1
)	0
on	0
the	0
neutral	0
and	0
acidic	0
biosynthetic	0
pathways	0
of	0
bile	1
salt	2
(	0
BS	1
)	0
synthesis	0
were	0
evaluated	0
in	0
rats	0
with	0
an	0
intact	0
enterohepatic	0
circulation	0
and	0
in	0
rats	0
with	0
long	0
-	0
term	0
bile	0
diversion	0
to	0
induce	0
BS	1
synthesis	0
.	0

For	0
this	0
purpose	0
,	0
bile	1
salt	2
pool	0
composition	0
,	0
synthesis	0
of	0
individual	0
BS	1
in	0
vivo	0
,	0
hepatic	0
activities	0
,	0
and	0
expression	0
levels	0
of	0
cholesterol	1
7alpha	0
-	0
hydroxylase	0
(	0
CYP7A	0
)	0
,	0
and	0
sterol	1
27	0
-	0
hydroxylase	0
(	0
CYP27	0
)	0
,	0
as	0
well	0
as	0
of	0
other	0
enzymes	0
involved	0
in	0
BS	1
synthesis	0
,	0
were	0
analyzed	0
in	0
rats	0
treated	0
with	0
EE	1
(	0
5	0
mg	0
/	0
kg	0
,	0
3	0
days	0
)	0
or	0
its	0
vehicle	0
.	0

BS	1
pool	0
size	0
was	0
decreased	0
by	0
27	0
%	0
but	0
total	0
BS	1
synthesis	0
was	0
not	0
affected	0
by	0
EE	1
in	0
intact	0
rats	0
.	0

Synthesis	0
of	0
cholate	1
was	0
reduced	0
by	0
68	0
%	0
in	0
EE	1
-	0
treated	0
rats	0
,	0
while	0
that	0
of	0
chenodeoxycholate	1
was	0
increased	0
by	0
60	0
%	0
.	0

The	0
recently	0
identified	0
Delta22	0
-	0
isomer	0
of	0
beta	0
-	0
muricholate	0
contributed	0
for	0
5	0
.	0
4	0
%	0
and	0
18	0
.	0
3	0
%	0
(	0
P	0
<	0
0	0
.	0
01	0
)	0
to	0
the	0
pool	0
in	0
control	0
and	0
EE	1
-	0
treated	0
rats	0
,	0
respectively	0
,	0
but	0
could	0
not	0
be	0
detected	0
in	0
bile	0
after	0
exhaustion	0
of	0
the	0
pool	0
.	0

A	0
clear	0
reduction	0
of	0
BS	1
synthesis	0
was	0
found	0
in	0
bile	0
-	0
diverted	0
rats	0
treated	0
with	0
EE	1
,	0
yet	0
biliary	0
BS	1
composition	0
was	0
only	0
minimally	0
affected	0
.	0

Activity	0
of	0
CYP7A	0
was	0
decreased	0
by	0
EE	1
in	0
both	0
intact	0
and	0
bile	0
-	0
diverted	0
rats	0
,	0
whereas	0
the	0
activity	0
of	0
the	0
CYP27	0
was	0
not	0
affected	0
.	0

Hepatic	0
mRNA	0
levels	0
of	0
CYP7A	0
were	0
significantly	0
reduced	0
by	0
EE	1
in	0
bile	0
-	0
diverted	0
rats	0
only	0
;	0
CYP27	0
mRNA	0
levels	0
were	0
not	0
affected	0
by	0
EE	1
.	0

In	0
addition	0
,	0
mRNA	0
levels	0
of	0
sterol	1
12alpha	0
-	0
hydroxylase	0
and	0
lithocholate	0
6beta	0
-	0
hydroxylase	0
were	0
increased	0
by	0
bile	0
diversion	0
and	0
suppressed	0
by	0
EE	1
.	0

This	0
study	0
shows	0
that	0
17alpha	1
-	2
ethinylestradiol	2
(	0
EE	1
)	0
-	0
induced	0
intrahepatic	3
cholestasis	4
in	0
rats	0
is	0
associated	0
with	0
selective	0
inhibition	0
of	0
the	0
neutral	0
pathway	0
of	0
bile	1
salt	2
(	0
BS	1
)	0
synthesis	0
.	0

Simultaneous	0
impairment	0
of	0
other	0
enzymes	0
in	0
the	0
BS	1
biosynthetic	0
pathways	0
may	0
contribute	0
to	0
overall	0
effects	0
of	0
EE	1
on	0
BS	1
synthesis	0
.	0

Glibenclamide	1
-	0
sensitive	0
hypotension	3
produced	0
by	0
helodermin	1
assessed	0
in	0
the	0
rat	0
.	0

The	0
effects	0
of	0
helodermin	1
,	0
a	0
basic	0
35	0
-	0
amino	1
acid	2
peptide	0
isolated	0
from	0
the	0
venom	0
of	0
a	0
lizard	0
salivary	0
gland	0
,	0
on	0
arterial	0
blood	0
pressure	0
and	0
heart	0
rate	0
were	0
examined	0
in	0
the	0
rat	0
,	0
focusing	0
on	0
the	0
possibility	0
that	0
activation	0
of	0
ATP	1
sensitive	0
K	1
+	0
(	0
K	1
(	0
ATP	1
)	0
)	0
channels	0
is	0
involved	0
in	0
the	0
responses	0
.	0

The	0
results	0
were	0
also	0
compared	0
with	0
those	0
of	0
vasoactive	0
intestinal	0
polypeptide	0
(	0
VIP	0
)	0
.	0

Helodermin	1
produced	0
hypotension	3
in	0
a	0
dose	0
-	0
dependent	0
manner	0
with	0
approximately	0
similar	0
potency	0
and	0
duration	0
to	0
VIP	0
.	0

Hypotension	3
induced	0
by	0
both	0
peptides	0
was	0
significantly	0
attenuated	0
by	0
glibenclamide	1
,	0
which	0
abolished	0
a	0
levcromakalim	1
-	0
produced	0
decrease	0
in	0
arterial	0
blood	0
pressure	0
.	0

0xyhemoglobin	0
did	0
not	0
affect	0
helodermin	1
-	0
induced	0
hypotension	3
,	0
whereas	0
it	0
shortened	0
the	0
duration	0
of	0
acetylcholine	1
(	0
ACh	1
)	0
-	0
produced	0
hypotension	3
.	0

These	0
findings	0
suggest	0
that	0
helodermin	1
-	0
produced	0
hypotension	3
is	0
partly	0
attributable	0
to	0
the	0
activation	0
of	0
glibenclamide	1
-	0
sensitive	0
K	1
+	0
channels	0
(	0
K	1
(	0
ATP	1
)	0
channels	0
)	0
,	0
which	0
presumably	0
exist	0
on	0
arterial	0
smooth	0
muscle	0
cells	0
.	0

EDRF	0
(	0
endothelium	0
-	0
derived	0
relaxing	0
factor	0
)	0
/	0
nitric	1
oxide	2
does	0
not	0
seem	0
to	0
play	0
an	0
important	0
role	0
in	0
the	0
peptide	0
-	0
produced	0
hypotension	3
.	0

Long	0
-	0
term	0
efficacy	0
and	0
adverse	0
event	0
of	0
nifedipine	1
sustained	0
-	0
release	0
tablets	0
for	0
cyclosporin	1
A	2
-	0
induced	0
hypertension	3
in	0
patients	0
with	0
psoriasis	3
.	0

Thirteen	0
psoriatic	3
patients	0
with	0
hypertension	3
during	0
the	0
course	0
of	0
cyclosporin	1
A	2
therapy	0
were	0
treated	0
for	0
25	0
months	0
with	0
a	0
calcium	1
channel	0
blocker	0
,	0
sustained	0
-	0
release	0
nifedipine	1
,	0
to	0
study	0
the	0
clinical	0
antihypertensive	0
effects	0
and	0
adverse	0
events	0
during	0
treatment	0
with	0
both	0
drugs	0
.	0

Seven	0
of	0
the	0
13	0
patients	0
had	0
exhibited	0
a	0
subclinical	0
hypertensive	3
state	0
before	0
cyclosporin	1
A	2
therapy	0
.	0

Both	0
systolic	0
and	0
diastolic	0
blood	0
pressures	0
of	0
these	0
13	0
patients	0
were	0
decreased	0
significantly	0
after	0
4	0
weeks	0
of	0
nifedipine	1
therapy	0
,	0
and	0
blood	0
pressure	0
was	0
maintained	0
within	0
the	0
normal	0
range	0
thereafter	0
for	0
25	0
months	0
.	0

The	0
adverse	0
events	0
during	0
combined	0
therapy	0
with	0
cyclosporin	1
A	2
and	0
nifedipine	1
included	0
an	0
increase	0
in	0
blood	1
urea	2
nitrogen	2
levels	0
in	0
9	0
of	0
the	0
13	0
patients	0
and	0
development	0
of	0
gingival	3
hyperplasia	4
in	0
2	0
of	0
the	0
13	0
patients	0
.	0

0ur	0
findings	0
indicate	0
that	0
sustained	0
-	0
release	0
nifedipine	1
is	0
useful	0
for	0
hypertensive	3
psoriatic	3
patients	0
under	0
long	0
-	0
term	0
treatment	0
with	0
cyclosporin	1
A	2
,	0
but	0
that	0
these	0
patients	0
should	0
be	0
monitored	0
for	0
gingival	3
hyperplasia	4
.	0

Selegiline	1
-	0
induced	0
postural	3
hypotension	4
in	0
Parkinson	3
'	4
s	4
disease	4
:	0
a	0
longitudinal	0
study	0
on	0
the	0
effects	0
of	0
drug	0
withdrawal	0
.	0
0BJECTIVES	0
:	0
The	0
United	0
Kingdom	0
Parkinson	3
'	4
s	4
Disease	4
Research	0
Group	0
(	0
UKPDRG	0
)	0
trial	0
found	0
an	0
increased	0
mortality	0
in	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
randomized	0
to	0
receive	0
10	0
mg	0
selegiline	1
per	0
day	0
and	0
L	1
-	2
dopa	2
compared	0
with	0
those	0
taking	0
L	1
-	2
dopa	2
alone	0
.	0
Recently	0
","	0
we	0
found	0
that	0
therapy	0
with	0
selegiline	1
and	0
L	1
-	2
dopa	2
was	0
associated	0
with	0
selective	0
systolic	3
orthostatic	4
hypotension	4
which	0
was	0
abolished	0
by	0
withdrawal	0
of	0
selegiline	1
.	0
This	0
unwanted	0
effect	0
on	0
postural	0
blood	0
pressure	0
was	0
not	0
the	0
result	0
of	0
underlying	0
autonomic	0
failure	0
.	0
The	0
aims	0
of	0
this	0
study	0
were	0
to	0
confirm	0
our	0
previous	0
findings	0
in	0
a	0
separate	0
cohort	0
of	0
patients	0
and	0
to	0
determine	0
the	0
time	0
course	0
of	0
the	0
cardiovascular	0
consequences	0
of	0
stopping	0
selegiline	1
in	0
the	0
expectation	0
that	0
this	0
might	0
shed	0
light	0
on	0
the	0
mechanisms	0
by	0
which	0
the	0
drug	0
causes	0
orthostatic	3
hypotension	4
.	0
METH0DS	0
:	0
The	0
cardiovascular	0
responses	0
to	0
standing	0
and	0
head	0
-	0
up	0
tilt	0
were	0
studied	0
repeatedly	0
in	0
PD	3
patients	0
receiving	0
selegiline	1
and	0
as	0
the	0
drug	0
was	0
withdrawn	0
.	0
RESULTS	0
:	0
Head	0
-	0
up	0
tilt	0
caused	0
systolic	3
orthostatic	4
hypotension	4
which	0
was	0
marked	0
in	0
six	0
of	0
20	0
PD	3
patients	0
on	0
selegiline	1
","	0
one	0
of	0
whom	0
lost	0
consciousness	0
with	0
unrecordable	0
blood	0
pressures	0
.	0
A	0
lesser	0
degree	0
of	0
orthostatic	3
hypotension	4
occurred	0
with	0
standing	0
.	0
0rthostatic	3
hypotension	4
was	0
ameliorated	0
4	0
days	0
after	0
withdrawal	0
of	0
selegiline	1
and	0
totally	0
abolished	0
7	0
days	0
after	0
discontinuation	0
of	0
the	0
drug	0
.	0
Stopping	0
selegiline	1
also	0
significantly	0
reduced	3
the	4
supine	4
systolic	4
and	4
diastolic	4
blood	4
pressures	4
consistent	0
with	0
a	0
previously	0
undescribed	0
supine	0
pressor	0
action	0
.	0
C0NCLUSI0N	0
:	0
This	0
study	0
confirms	0
our	0
previous	0
finding	0
that	0
selegiline	1
in	0
combination	0
with	0
L	1
-	2
dopa	2
is	0
associated	0
with	0
selective	0
orthostatic	3
hypotension	4
.	0
The	0
possibilities	0
that	0
these	0
cardiovascular	0
findings	0
might	0
be	0
the	0
result	0
of	0
non	0
-	0
selective	0
inhibition	0
of	0
monoamine	0
oxidase	0
or	0
of	0
amphetamine	1
and	0
metamphetamine	1
are	0
discussed	0
.	0
Further	0
studies	0
on	0
effects	0
of	0
irrigation	0
solutions	0
on	0
rat	0
bladders	0
.	0
Further	0
studies	0
on	0
the	0
effects	0
of	0
certain	0
irrigating	0
fluids	0
on	0
the	0
rat	0
bladder	0
for	0
18	0
hours	0
are	0
reported	0
.	0
The	0
results	0
have	0
shown	0
that	0
the	0
degradation	0
product	0
p	1
-	2
choloroaniline	2
is	0
not	0
a	0
significant	0
factor	0
in	0
chlorhexidine	1
-	2
digluconate	2
associated	0
erosive	0
cystitis	3
.	0
A	0
high	0
percentage	0
of	0
kanamycin	1
-	0
colistin	1
and	0
povidone	1
-	2
iodine	2
irrigations	0
were	0
associated	0
with	0
erosive	0
cystitis	3
and	0
suggested	0
a	0
possible	0
complication	0
with	0
human	0
usage	0
.	0
Picloxydine	1
irrigations	0
appeared	0
to	0
have	0
a	0
lower	0
incidence	0
of	0
erosive	0
cystitis	3
but	0
further	0
studies	0
would	0
have	0
to	0
be	0
performed	0
before	0
it	0
could	0
be	0
recommended	0
for	0
use	0
in	0
urological	0
procedures	0
.	0
Effects	0
of	0
tetrandrine	1
and	0
fangchinoline	1
on	0
experimental	0
thrombosis	3
in	0
mice	0
and	0
human	0
platelet	3
aggregation	4
.	0
Tetrandrine	1
(	0
TET	1
)	0
and	0
fangchinoline	1
(	0
FAN	1
)	0
are	0
two	0
naturally	0
occurring	0
analogues	0
with	0
a	0
bisbenzylisoquinoline	1
structure	0
.	0
The	0
present	0
study	0
was	0
undertaken	0
to	0
investigate	0
the	0
effects	0
of	0
TET	1
and	0
FAN	1
on	0
the	0
experimental	0
thrombosis	3
induced	0
by	0
collagen	0
plus	0
epinephrine	1
(	0
EP	1
)	0
in	0
mice	0
","	0
and	0
platelet	3
aggregation	4
and	0
blood	3
coagulation	4
in	0
vitro	0
.	0
In	0
the	0
in	0
vivo	0
study	0
","	0
the	0
administration	0
(	0
50	0
mg	0
/	0
kg	0
","	0
i	0
.	0
p	0
.	0
)	0
of	0
TET	1
and	0
FAN	1
in	0
mice	0
showed	0
the	0
inhibition	0
of	0
thrombosis	3
by	0
55	0
%	0
and	0
35	0
%	0
","	0
respectively	0
","	0
while	0
acetylsalicylic	1
acid	2
(	0
ASA	1
","	0
50	0
mg	0
/	0
kg	0
","	0
i	0
.	0
p	0
.	0
)	0
","	0
a	0
positive	0
control	0
","	0
showed	0
only	0
30	0
%	0
inhibition	0
.	0
In	0
the	0
vitro	0
human	0
platelet	3
aggregations	4
induced	0
by	0
the	0
agonists	0
used	0
in	0
tests	0
","	0
TET	1
and	0
FAN	1
showed	0
the	0
inhibitions	0
dose	0
dependently	0
.	0
In	0
addition	0
","	0
neither	0
TET	1
nor	0
FAN	1
showed	0
any	0
anticoagulation	0
activities	0
in	0
the	0
measurement	0
of	0
the	0
activated	0
partial	0
thromboplastin	0
time	0
(	0
APTT	0
)	0
","	0
prothrombin	0
time	0
(	0
PT	0
)	0
and	0
thrombin	0
time	0
(	0
TT	0
)	0
using	0
human	0
-	0
citrated	0
plasma	0
.	0
These	0
results	0
suggest	0
that	0
antithrombosis	0
of	0
TET	1
and	0
FAN	1
in	0
mice	0
may	0
be	0
mainly	0
related	0
to	0
the	0
antiplatelet	0
aggregation	0
activities	0
.	0
Angioedema	3
due	0
to	0
ACE	1
inhibitors	2
:	0
common	0
and	0
inadequately	0
diagnosed	0
.	0
The	0
estimated	0
incidence	0
of	0
angioedema	3
during	0
angiotensin	1
-	2
converting	2
enzyme	2
(	2
ACE	2
)	2
inhibitor	2
treatment	0
is	0
between	0
1	0
and	0
7	0
per	0
thousand	0
patients	0
.	0
This	0
potentially	0
serious	0
adverse	0
effect	0
is	0
often	0
preceded	0
by	0
minor	0
manifestations	0
that	0
may	0
serve	0
as	0
a	0
warning	0
.	0
Cocaine	1
-	0
induced	0
mood	3
disorder	4
:	0
prevalence	0
rates	0
and	0
psychiatric	3
symptoms	0
in	0
an	0
outpatient	0
cocaine	1
-	0
dependent	0
sample	0
.	0
This	0
paper	0
attempts	0
to	0
examine	0
and	0
compare	0
prevalence	0
rates	0
and	0
symptom	0
patterns	0
of	0
DSM	0
substance	0
-	0
induced	0
and	0
other	0
mood	3
disorders	4
.	0
243	0
cocaine	1
-	0
dependent	0
outpatients	0
with	0
cocaine	1
-	0
induced	0
mood	3
disorder	4
(	0
CIMD	3
)	0
","	0
other	0
mood	3
disorders	4
","	0
or	0
no	0
mood	3
disorder	4
were	0
compared	0
on	0
measures	0
of	0
psychiatric	3
symptoms	0
.	0
The	0
prevalence	0
rate	0
for	0
CIMD	3
was	0
12	0
%	0
at	0
baseline	0
.	0
Introduction	0
of	0
the	0
DSM	0
-	0
IV	0
diagnosis	0
of	0
CIMD	3
did	0
not	0
substantially	0
affect	0
rates	0
of	0
the	0
other	0
depressive	3
disorders	4
.	0
Patients	0
with	0
CIMD	3
had	0
symptom	0
severity	0
levels	0
between	0
those	0
of	0
patients	0
with	0
and	0
without	0
a	0
mood	3
disorder	4
.	0
These	0
findings	0
suggest	0
some	0
validity	0
for	0
the	0
new	0
DSM	0
-	0
IV	0
diagnosis	0
of	0
CIMD	3
","	0
but	0
also	0
suggest	0
that	0
it	0
requires	0
further	0
specification	0
and	0
replication	0
.	0
Effect	0
of	0
fucoidan	1
treatment	0
on	0
collagenase	0
-	0
induced	0
intracerebral	3
hemorrhage	4
in	0
rats	0
.	0
Inflammatory	0
cells	0
are	0
postulated	0
to	0
mediate	0
some	0
of	0
the	0
brain	3
damage	4
following	0
ischemic	3
stroke	4
.	0
Intracerebral	3
hemorrhage	4
is	0
associated	0
with	0
more	0
inflammation	3
than	0
ischemic	3
stroke	4
.	0
We	0
tested	0
the	0
sulfated	0
polysaccharide	0
fucoidan	1
","	0
which	0
has	0
been	0
reported	0
to	0
reduce	0
inflammatory	0
brain	3
damage	4
","	0
in	0
a	0
rat	0
model	0
of	0
intracerebral	3
hemorrhage	4
induced	0
by	0
injection	0
of	0
bacterial	0
collagenase	0
into	0
the	0
caudate	0
nucleus	0
.	0
Rats	0
were	0
treated	0
with	0
seven	0
day	0
intravenous	0
infusion	0
of	0
fucoidan	1
(	0
30	0
micrograms	0
h	0
-	0
1	0
)	0
or	0
vehicle	0
.	0
The	0
hematoma	3
was	0
assessed	0
in	0
vivo	0
by	0
magnetic	0
resonance	0
imaging	0
.	0
Motor	0
behavior	0
","	0
passive	0
avoidance	0
","	0
and	0
skilled	0
forelimb	0
function	0
were	0
tested	0
repeatedly	0
for	0
six	0
weeks	0
.	0
Fucoidan	1
-	0
treated	0
rats	0
exhibited	0
evidence	0
of	0
impaired	3
blood	4
clotting	4
and	0
hemodilution	3
","	0
had	0
larger	0
hematomas	3
","	0
and	0
tended	0
to	0
have	0
less	0
inflammation	3
in	0
the	0
vicinity	0
of	0
the	0
hematoma	3
after	0
three	0
days	0
.	0
They	0
showed	0
significantly	0
more	0
rapid	0
improvement	0
of	0
motor	0
function	0
in	0
the	0
first	0
week	0
following	0
hemorrhage	3
and	0
better	0
memory	0
retention	0
in	0
the	0
passive	0
avoidance	0
test	0
.	0
Acute	0
white	3
matter	4
edema	4
and	0
eventual	0
neuronal	3
loss	4
in	0
the	0
striatum	0
adjacent	0
to	0
the	0
hematoma	3
did	0
not	0
differ	0
between	0
the	0
two	0
groups	0
.	0
Investigation	0
of	0
more	0
specific	0
anti	0
-	0
inflammatory	0
agents	0
and	0
hemodiluting	0
agents	0
are	0
warranted	0
in	0
intracerebral	3
hemorrhage	4
.	0
Recurarization	0
in	0
the	0
recovery	0
room	0
.	0
A	0
case	0
of	0
recurarization	0
in	0
the	0
recovery	0
room	0
is	0
reported	0
.	0
Accumulation	0
of	0
atracurium	1
in	0
the	0
intravenous	0
line	0
led	0
to	0
recurarization	0
after	0
flushing	0
the	0
line	0
in	0
the	0
recovery	0
room	0
.	0
A	0
respiratory	3
arrest	4
with	0
severe	0
desaturation	3
and	0
bradycardia	3
occurred	0
.	0
Circumstances	0
leading	0
to	0
this	0
event	0
and	0
the	0
mechanisms	0
enabling	0
a	0
neuromuscular	3
blockade	4
to	0
occur	0
","	0
following	0
the	0
administration	0
of	0
a	0
small	0
dose	0
of	0
relaxant	0
","	0
are	0
discussed	0
.	0
The	0
haemodynamic	0
effects	0
of	0
propofol	1
in	0
combination	0
with	0
ephedrine	1
in	0
elderly	0
patients	0
(	0
ASA	0
groups	0
3	0
and	0
4	0
)	0
.	0
The	0
marked	0
vasodilator	0
and	0
negative	0
inotropic	0
effects	0
of	0
propofol	1
are	0
disadvantages	0
in	0
frail	0
elderly	0
patients	0
.	0
We	0
investigated	0
the	0
safety	0
and	0
efficacy	0
of	0
adding	0
different	0
doses	0
of	0
ephedrine	1
to	0
propofol	1
in	0
order	0
to	0
obtund	0
the	0
hypotensive	3
response	0
.	0
The	0
haemodynamic	0
effects	0
of	0
adding	0
15	0
","	0
20	0
or	0
25	0
mg	0
of	0
ephedrine	1
to	0
200	0
mg	0
of	0
propofol	1
were	0
compared	0
to	0
control	0
in	0
40	0
ASA	0
3	0
/	0
4	0
patients	0
over	0
60	0
years	0
presenting	0
for	0
genito	0
-	0
urinary	0
surgery	0
.	0
The	0
addition	0
of	0
ephedrine	1
to	0
propofol	1
appears	0
to	0
be	0
an	0
effective	0
method	0
of	0
obtunding	0
the	0
hypotensive	3
response	0
to	0
propofol	1
at	0
all	0
doses	0
used	0
in	0
this	0
study	0
.	0
However	0
","	0
marked	0
tachycardia	3
associated	0
with	0
the	0
use	0
of	0
ephedrine	1
in	0
combination	0
with	0
propofol	1
occurred	0
in	0
the	0
majority	0
of	0
patients	0
","	0
occasionally	0
reaching	0
high	0
levels	0
in	0
individual	0
patients	0
.	0
Due	0
to	0
the	0
risk	0
of	0
this	0
tachycardia	3
inducing	0
myocardial	3
ischemia	4
","	0
we	0
would	0
not	0
recommend	0
the	0
use	0
in	0
elderly	0
patients	0
of	0
any	0
of	0
the	0
ephedrine	1
/	0
propofol	1
/	0
mixtures	0
studied	0
.	0
Gemcitabine	1
plus	0
vinorelbine	1
in	0
nonsmall	3
cell	4
lung	4
carcinoma	4
patients	0
age	0
70	0
years	0
or	0
older	0
or	0
patients	0
who	0
cannot	0
receive	0
cisplatin	1
.	0
0ncopaz	0
Cooperative	0
Group	0
.	0
BACKGR0UND	0
:	0
Although	0
the	0
prevalence	0
of	0
nonsmall	3
cell	4
lung	4
carcinoma	4
(	0
NSCLC	3
)	0
is	0
high	0
among	0
elderly	0
patients	0
","	0
few	0
data	0
are	0
available	0
regarding	0
the	0
efficacy	0
and	0
toxicity	3
of	0
chemotherapy	0
in	0
this	0
group	0
of	0
patients	0
.	0
Recent	0
reports	0
indicate	0
that	0
single	0
agent	0
therapy	0
with	0
vinorelbine	1
(	0
VNB	1
)	0
or	0
gemcitabine	1
(	0
GEM	1
)	0
may	0
obtain	0
a	0
response	0
rate	0
of	0
20	0
-	0
30	0
%	0
in	0
elderly	0
patients	0
","	0
with	0
acceptable	0
toxicity	3
and	0
improvement	0
in	0
symptoms	0
and	0
quality	0
of	0
life	0
.	0
In	0
the	0
current	0
study	0
the	0
efficacy	0
and	0
toxicity	3
of	0
the	0
combination	0
of	0
GEM	1
and	0
VNB	1
in	0
elderly	0
patients	0
with	0
advanced	0
NSCLC	3
or	0
those	0
with	0
some	0
contraindication	0
to	0
receiving	0
cisplatin	1
were	0
assessed	0
.	0
METH0DS	0
:	0
Forty	0
-	0
nine	0
patients	0
with	0
advanced	0
NSCLC	3
were	0
included	0
","	0
38	0
of	0
whom	0
were	0
age	0
>	0
/	0
=	0
70	0
years	0
and	0
11	0
were	0
age	0
<	0
70	0
years	0
but	0
who	0
had	0
some	0
contraindication	0
to	0
receiving	0
cisplatin	1
.	0
All	0
patients	0
were	0
evaluable	0
for	0
response	0
and	0
toxicity	3
.	0
Treatment	0
was	0
comprised	0
of	0
VNB	1
","	0
25	0
mg	0
/	0
m	0
(	0
2	0
)	0
","	0
plus	0
GEM	1
","	0
1000	0
mg	0
/	0
m	0
(	0
2	0
)	0
","	0
both	0
on	0
Days	0
1	0
","	0
8	0
","	0
and	0
15	0
every	0
28	0
days	0
.	0
Patients	0
received	0
a	0
minimum	0
of	0
three	0
courses	0
unless	0
progressive	0
disease	0
was	0
detected	0
.	0
RESULTS	0
:	0
0ne	0
hundred	0
sixty	0
-	0
five	0
courses	0
were	0
administered	0
","	0
with	0
a	0
median	0
of	0
3	0
.	0
6	0
courses	0
per	0
patient	0
.	0
The	0
overall	0
response	0
rate	0
was	0
26	0
%	0
(	0
95	0
%	0
confidence	0
interval	0
","	0
15	0
-	0
41	0
%	0
)	0
.	0
Two	0
patients	0
attained	0
a	0
complete	0
response	0
(	0
4	0
%	0
)	0
and	0
11	0
patients	0
(	0
22	0
%	0
)	0
achieved	0
a	0
partial	0
response	0
.	0
Eastern	0
Cooperative	0
0ncology	0
Group	0
performance	0
status	0
improved	0
in	0
35	0
%	0
of	0
those	0
patients	0
with	0
an	0
initial	0
value	0
>	0
0	0
","	0
whereas	0
relief	0
of	0
at	0
least	0
1	0
symptom	0
without	0
worsening	0
of	0
other	0
symptoms	0
was	0
noted	0
in	0
27	0
patients	0
(	0
55	0
%	0
)	0
.	0
The	0
median	0
time	0
to	0
progression	0
was	0
16	0
weeks	0
and	0
the	0
1	0
-	0
year	0
survival	0
rate	0
was	0
33	0
%	0
.	0
Toxicity	3
was	0
mild	0
.	0
Six	0
patients	0
(	0
12	0
%	0
)	0
had	0
World	0
Health	0
0rganization	0
Grade	0
3	0
-	0
4	0
neutropenia	3
","	0
2	0
patients	0
(	0
4	0
%	0
)	0
had	0
Grade	0
3	0
-	0
4	0
thrombocytopenia	3
","	0
and	0
2	0
patients	0
(	0
4	0
%	0
)	0
had	0
Grade	0
3	0
neurotoxicity	3
.	0
Three	0
patients	0
with	0
severe	0
neutropenia	3
(	0
6	0
%	0
)	0
died	0
of	0
sepsis	3
.	0
The	0
median	0
age	0
of	0
those	0
patients	0
developing	0
Grade	0
3	0
-	0
4	0
neutropenia	3
was	0
significantly	0
higher	0
than	0
that	0
of	0
the	0
remaining	0
patients	0
(	0
75	0
years	0
vs	0
.	0
72	0
years	0
;	0
P	0
=	0
0	0
.	0
47	0
)	0
.	0
C0NCLUSI0NS	0
:	0
The	0
combination	0
of	0
GEM	1
and	0
VNB	1
is	0
moderately	0
active	0
and	0
well	0
tolerated	0
except	0
in	0
patients	0
age	0
>	0
/	0
=	0
75	0
years	0
.	0
This	0
age	0
group	0
had	0
an	0
increased	0
risk	0
of	0
myelosuppression	3
.	0
Therefore	0
the	0
prophylactic	0
use	0
of	0
granulocyte	0
-	0
colony	0
stimulating	0
factor	0
should	0
be	0
considered	0
with	0
this	0
treatment	0
.	0
New	0
chemotherapy	0
combinations	0
with	0
higher	0
activity	0
and	0
lower	0
toxicity	3
are	0
needed	0
for	0
elderly	0
patients	0
with	0
advanced	0
NSCLC	3
.	0
A	0
selective	0
dopamine	1
D4	0
receptor	0
antagonist	0
","	0
NRA0160	1
:	0
a	0
preclinical	0
neuropharmacological	0
profile	0
.	0
NRA0160	1
","	0
5	1
-	2
[	2
2	2
-	2
(	2
4	2
-	2
(	2
3	2
-	2
fluorobenzylidene	2
)	2
piperidin	2
-	2
1	2
-	2
yl	2
)	2
ethyl	2
]	2
-	2
4	2
-	2
(	2
4	2
-	2
fluorophenyl	2
)	2
thiazole	2
-	2
2	2
-	2
carboxamide	2
","	0
has	0
a	0
high	0
affinity	0
for	0
human	0
cloned	0
dopamine	1
D4	0
.	0
2	0
","	0
D4	0
.	0
4	0
and	0
D4	0
.	0
7	0
receptors	0
","	0
with	0
Ki	0
values	0
of	0
0	0
.	0
5	0
","	0
0	0
.	0
9	0
and	0
2	0
.	0
7	0
nM	0
","	0
respectively	0
.	0
NRA0160	1
is	0
over	0
20	0
","	0
000fold	0
more	0
potent	0
at	0
the	0
dopamine	1
D4	0
.	0
2	0
receptor	0
compared	0
with	0
the	0
human	0
cloned	0
dopamine	1
D2L	0
receptor	0
.	0
NRA0160	1
has	0
negligible	0
affinity	0
for	0
the	0
human	0
cloned	0
dopamine	1
D3	0
receptor	0
(	0
Ki	0
=	0
39	0
nM	0
)	0
","	0
rat	0
serotonin	1
(	0
5	1
-	2
HT	2
)	0
2A	0
receptors	0
(	0
Ki	0
=	0
180	0
nM	0
)	0
and	0
rat	0
alpha1	0
adrenoceptor	0
(	0
Ki	0
=	0
237	0
nM	0
)	0
.	0
NRA0160	1
and	0
clozapine	1
antagonized	0
locomotor	0
hyperactivity	3
induced	0
by	0
methamphetamine	1
(	0
MAP	1
)	0
in	0
mice	0
.	0
NRA0160	1
and	0
clozapine	1
antagonized	0
MAP	1
-	0
induced	0
stereotyped	0
behavior	0
in	0
mice	0
","	0
although	0
their	0
effects	0
did	0
not	0
exceed	0
50	0
%	0
inhibition	0
","	0
even	0
at	0
the	0
highest	0
dose	0
given	0
.	0
NRA0160	1
and	0
clozapine	1
significantly	0
induced	0
catalepsy	3
in	0
rats	0
","	0
although	0
their	0
effects	0
did	0
not	0
exceed	0
50	0
%	0
induction	0
even	0
at	0
the	0
highest	0
dose	0
given	0
.	0
NRA0160	1
and	0
clozapine	1
significantly	0
reversed	0
the	0
disruption	0
of	0
prepulse	0
inhibition	0
(	0
PPI	0
)	0
in	0
rats	0
produced	0
by	0
apomorphine	1
.	0
NRA0160	1
and	0
clozapine	1
significantly	0
shortened	0
the	0
phencyclidine	1
(	0
PCP	1
)	0
-	0
induced	0
prolonged	0
swimming	0
latency	0
in	0
rats	0
in	0
a	0
water	0
maze	0
task	0
.	0
These	0
findings	0
suggest	0
that	0
NRA0160	1
may	0
have	0
unique	0
antipsychotic	0
activities	0
without	0
the	0
liability	0
of	0
motor	0
side	0
effects	0
typical	0
of	0
classical	0
antipsychotics	0
.	0
Warfarin	1
-	0
induced	0
artery	3
calcification	4
is	0
accelerated	0
by	0
growth	0
and	0
vitamin	1
D	2
.	0
The	0
present	0
studies	0
demonstrate	0
that	0
growth	0
and	0
vitamin	1
D	2
treatment	0
enhance	0
the	0
extent	0
of	0
artery	3
calcification	4
in	0
rats	0
given	0
sufficient	0
doses	0
of	0
Warfarin	1
to	0
inhibit	0
gamma	0
-	0
carboxylation	0
of	0
matrix	0
Gla	0
protein	0
","	0
a	0
calcification	3
inhibitor	0
known	0
to	0
be	0
expressed	0
by	0
smooth	0
muscle	0
cells	0
and	0
macrophages	0
in	0
the	0
artery	0
wall	0
.	0
The	0
first	0
series	0
of	0
experiments	0
examined	0
the	0
influence	0
of	0
age	0
and	0
growth	0
status	0
on	0
artery	3
calcification	4
in	0
Warfarin	1
-	0
treated	0
rats	0
.	0
Treatment	0
for	0
2	0
weeks	0
with	0
Warfarin	1
caused	0
massive	0
focal	0
calcification	3
of	4
the	4
artery	4
media	0
in	0
20	0
-	0
day	0
-	0
old	0
rats	0
and	0
less	0
extensive	0
focal	0
calcification	3
in	0
42	0
-	0
day	0
-	0
old	0
rats	0
.	0
In	0
contrast	0
","	0
no	0
artery	3
calcification	4
could	0
be	0
detected	0
in	0
10	0
-	0
month	0
-	0
old	0
adult	0
rats	0
even	0
after	0
4	0
weeks	0
of	0
Warfarin	1
treatment	0
.	0
To	0
directly	0
examine	0
the	0
importance	0
of	0
growth	0
to	0
Warfarin	1
-	0
induced	0
artery	3
calcification	4
in	0
animals	0
of	0
the	0
same	0
age	0
","	0
20	0
-	0
day	0
-	0
old	0
rats	0
were	0
fed	0
for	0
2	0
weeks	0
either	0
an	0
ad	0
libitum	0
diet	0
or	0
a	0
6	0
-	0
g	0
/	0
d	0
restricted	0
diet	0
that	0
maintains	0
weight	0
but	0
prevents	0
growth	0
.	0
Concurrent	0
treatment	0
of	0
both	0
dietary	0
groups	0
with	0
Warfarin	1
produced	0
massive	0
focal	0
calcification	3
of	4
the	4
artery	4
media	0
in	0
the	0
ad	0
libitum	0
-	0
fed	0
rats	0
but	0
no	0
detectable	0
artery	3
calcification	4
in	0
the	0
restricted	0
-	0
diet	0
","	0
growth	0
-	0
inhibited	0
group	0
.	0
Although	0
the	0
explanation	0
for	0
the	0
association	0
between	0
artery	3
calcification	4
and	0
growth	0
status	0
cannot	0
be	0
determined	0
from	0
the	0
present	0
study	0
","	0
there	0
was	0
a	0
relationship	0
between	0
higher	0
serum	0
phosphate	1
and	0
susceptibility	0
to	0
artery	3
calcification	4
","	0
with	0
30	0
%	0
higher	0
levels	0
of	0
serum	0
phosphate	1
in	0
young	0
","	0
ad	0
libitum	0
-	0
fed	0
rats	0
compared	0
with	0
either	0
of	0
the	0
groups	0
that	0
was	0
resistant	0
to	0
Warfarin	1
-	0
induced	0
artery	3
calcification	4
","	0
ie	0
","	0
the	0
10	0
-	0
month	0
-	0
old	0
rats	0
and	0
the	0
restricted	0
-	0
diet	0
","	0
growth	0
-	0
inhibited	0
young	0
rats	0
.	0
This	0
observation	0
suggests	0
that	0
increased	0
susceptibility	0
to	0
Warfarin	1
-	0
induced	0
artery	3
calcification	4
could	0
be	0
related	0
to	0
higher	0
serum	0
phosphate	1
levels	0
.	0
The	0
second	0
set	0
of	0
experiments	0
examined	0
the	0
possible	0
synergy	0
between	0
vitamin	1
D	2
and	0
Warfarin	1
in	0
artery	3
calcification	4
.	0
High	0
doses	0
of	0
vitamin	1
D	2
are	0
known	0
to	0
cause	0
calcification	3
of	4
the	4
artery	4
media	0
in	0
as	0
little	0
as	0
3	0
to	0
4	0
days	0
.	0
High	0
doses	0
of	0
the	0
vitamin	1
K	2
antagonist	0
Warfarin	1
are	0
also	0
known	0
to	0
cause	0
calcification	3
of	4
the	4
artery	4
media	0
","	0
but	0
at	0
treatment	0
times	0
of	0
2	0
weeks	0
or	0
longer	0
yet	0
not	0
at	0
1	0
week	0
.	0
In	0
the	0
current	0
study	0
","	0
we	0
investigated	0
the	0
synergy	0
between	0
these	0
2	0
treatments	0
and	0
found	0
that	0
concurrent	0
Warfarin	1
administration	0
dramatically	0
increased	0
the	0
extent	0
of	0
calcification	3
in	0
the	0
media	0
of	0
vitamin	1
D	2
-	0
treated	0
rats	0
at	0
3	0
and	0
4	0
days	0
.	0
There	0
was	0
a	0
close	0
parallel	0
between	0
the	0
effect	0
of	0
vitamin	1
D	2
dose	0
on	0
artery	3
calcification	4
and	0
the	0
effect	0
of	0
vitamin	1
D	2
dose	0
on	0
the	0
elevation	0
of	0
serum	0
calcium	1
","	0
which	0
suggests	0
that	0
vitamin	1
D	2
may	0
induce	0
artery	3
calcification	4
through	0
its	0
effect	0
on	0
serum	0
calcium	1
.	0
Because	0
Warfarin	1
treatment	0
had	0
no	0
effect	0
on	0
the	0
elevation	0
in	0
serum	0
calcium	1
produced	0
by	0
vitamin	1
D	2
","	0
the	0
synergy	0
between	0
Warfarin	1
and	0
vitamin	1
D	2
is	0
probably	0
best	0
explained	0
by	0
the	0
hypothesis	0
that	0
Warfarin	1
inhibits	0
the	0
activity	0
of	0
matrix	0
Gla	0
protein	0
as	0
a	0
calcification	3
inhibitor	0
.	0
High	0
levels	0
of	0
matrix	0
Gla	0
protein	0
are	0
found	0
at	0
sites	0
of	0
artery	3
calcification	4
in	0
rats	0
treated	0
with	0
vitamin	1
D	2
plus	0
Warfarin	1
","	0
and	0
chemical	0
analysis	0
showed	0
that	0
the	0
protein	0
that	0
accumulated	0
was	0
indeed	0
not	0
gamma	1
-	2
carboxylated	2
.	0
These	0
observations	0
indicate	0
that	0
although	0
the	0
gamma	1
-	2
carboxyglutamate	2
residues	0
of	0
matrix	0
Gla	0
protein	0
are	0
apparently	0
required	0
for	0
its	0
function	0
as	0
a	0
calcification	3
inhibitor	0
","	0
they	0
are	0
not	0
required	0
for	0
its	0
accumulation	0
at	0
calcification	3
sites	0
.	0
Test	0
conditions	0
influence	0
the	0
response	0
to	0
a	0
drug	0
challenge	0
in	0
rodents	0
.	0
These	0
studies	0
were	0
conducted	0
to	0
examine	0
the	0
differential	0
response	0
to	0
a	0
drug	0
challenge	0
under	0
varied	0
experimental	0
test	0
conditions	0
routinely	0
employed	0
to	0
study	0
drug	0
-	0
induced	0
behavioral	0
and	0
neurophysiological	0
responses	0
in	0
rodents	0
.	0
Apomorphine	1
","	0
a	0
nonselective	0
dopamine	1
agonist	2
","	0
was	0
selected	0
due	0
to	0
its	0
biphasic	0
behavioral	0
effects	0
","	0
its	0
ability	0
to	0
induce	0
hypothermia	3
","	0
and	0
to	0
produce	0
distinct	0
changes	0
to	0
dopamine	1
turnover	0
in	0
the	0
rodent	0
brain	0
.	0
From	0
such	0
experiments	0
there	0
is	0
evidence	0
that	0
characterization	0
and	0
detection	0
of	0
apomorphine	1
-	0
induced	0
activity	0
in	0
rodents	0
critically	0
depends	0
upon	0
the	0
test	0
conditions	0
employed	0
.	0
In	0
rats	0
","	0
detection	0
of	0
apomorphine	1
-	0
induced	0
hyperactivity	3
was	0
facilitated	0
by	0
a	0
period	0
of	0
acclimatization	0
to	0
the	0
test	0
conditions	0
.	0
Moreover	0
","	0
test	0
conditions	0
can	0
impact	0
upon	0
other	0
physiological	0
responses	0
to	0
apomorphine	1
such	0
as	0
drug	0
-	0
induced	0
hypothermia	3
.	0
In	0
mice	0
","	0
apomorphine	1
produced	0
qualitatively	0
different	0
responses	0
under	0
novel	0
conditions	0
when	0
compared	0
to	0
those	0
behaviors	0
elicited	0
in	0
the	0
home	0
test	0
cage	0
.	0
Drug	0
-	0
induced	0
gross	0
activity	0
counts	0
were	0
increased	0
in	0
the	0
novel	0
exploratory	0
box	0
only	0
","	0
while	0
measures	0
of	0
stereotypic	0
behavior	0
were	0
similar	0
in	0
both	0
.	0
By	0
contrast	0
","	0
apomorphine	1
-	0
induced	0
locomotion	0
was	0
more	0
prominent	0
in	0
the	0
novel	0
exploratory	0
box	0
.	0
Dopamine	1
turnover	0
ratios	0
(	0
D0PAC	1
:	0
DA	1
and	0
HVA	1
:	0
DA	1
)	0
were	0
found	0
to	0
be	0
lower	0
in	0
those	0
animals	0
exposed	0
to	0
the	0
exploratory	0
box	0
when	0
compared	0
to	0
their	0
home	0
cage	0
counterparts	0
.	0
However	0
","	0
apomorphine	1
-	0
induced	0
reductions	0
in	0
striatal	0
dopamine	1
turnover	0
were	0
detected	0
in	0
both	0
novel	0
and	0
home	0
cage	0
environments	0
.	0
The	0
implications	0
of	0
these	0
findings	0
are	0
discussed	0
with	0
particular	0
emphasis	0
upon	0
conducting	0
psychopharmacological	0
challenge	0
tests	0
in	0
rodents	0
.	0
Hemolysis	3
of	0
human	0
erythrocytes	0
induced	0
by	0
tamoxifen	1
is	0
related	0
to	0
disruption	0
of	0
membrane	0
structure	0
.	0
Tamoxifen	1
(	0
TAM	1
)	0
","	0
the	0
antiestrogenic	0
drug	0
most	0
widely	0
prescribed	0
in	0
the	0
chemotherapy	0
of	0
breast	3
cancer	4
","	0
induces	0
changes	0
in	0
normal	0
discoid	0
shape	0
of	0
erythrocytes	0
and	0
hemolytic	3
anemia	4
.	0
This	0
work	0
evaluates	0
the	0
effects	0
of	0
TAM	1
on	0
isolated	0
human	0
erythrocytes	0
","	0
attempting	0
to	0
identify	0
the	0
underlying	0
mechanisms	0
on	0
TAM	1
-	0
induced	0
hemolytic	3
anemia	4
and	0
the	0
involvement	0
of	0
biomembranes	0
in	0
its	0
cytostatic	0
action	0
mechanisms	0
.	0
TAM	1
induces	0
hemolysis	3
of	0
erythrocytes	0
as	0
a	0
function	0
of	0
concentration	0
.	0
The	0
extension	0
of	0
hemolysis	3
is	0
variable	0
with	0
erythrocyte	0
samples	0
","	0
but	0
12	0
.	0
5	0
microM	0
TAM	1
induces	0
total	0
hemolysis	3
of	0
all	0
tested	0
suspensions	0
.	0
Despite	0
inducing	0
extensive	0
erythrocyte	0
lysis	0
","	0
TAM	1
does	0
not	0
shift	0
the	0
osmotic	0
fragility	0
curves	0
of	0
erythrocytes	0
.	0
The	0
hemolytic	3
effect	0
of	0
TAM	1
is	0
prevented	0
by	0
low	0
concentrations	0
of	0
alpha	1
-	2
tocopherol	2
(	0
alpha	1
-	2
T	2
)	0
and	0
alpha	1
-	2
tocopherol	2
acetate	2
(	0
alpha	1
-	2
TAc	2
)	0
(	0
inactivated	0
functional	0
hydroxyl	1
)	0
indicating	0
that	0
TAM	1
-	0
induced	0
hemolysis	3
is	0
not	0
related	0
to	0
oxidative	0
membrane	0
damage	0
.	0
This	0
was	0
further	0
evidenced	0
by	0
absence	0
of	0
oxygen	1
consumption	0
and	0
hemoglobin	0
oxidation	0
both	0
determined	0
in	0
parallel	0
with	0
TAM	1
-	0
induced	0
hemolysis	3
.	0
Furthermore	0
","	0
it	0
was	0
observed	0
that	0
TAM	1
inhibits	0
the	0
peroxidation	0
of	0
human	0
erythrocytes	0
induced	0
by	0
AAPH	1
","	0
thus	0
ruling	0
out	0
TAM	1
-	0
induced	0
cell	0
oxidative	0
stress	0
.	0
Hemolysis	3
caused	0
by	0
TAM	1
was	0
not	0
preceded	0
by	0
the	0
leakage	0
of	0
K	1
(	0
+	0
)	0
from	0
the	0
cells	0
","	0
also	0
excluding	0
a	0
colloid	0
-	0
osmotic	0
type	0
mechanism	0
of	0
hemolysis	3
","	0
according	0
to	0
the	0
effects	0
on	0
osmotic	0
fragility	0
curves	0
.	0
However	0
","	0
TAM	1
induces	0
release	0
of	0
peripheral	0
proteins	0
of	0
membrane	0
-	0
cytoskeleton	0
and	0
cytosol	0
proteins	0
essentially	0
bound	0
to	0
band	0
3	0
.	0
Either	0
alpha	1
-	2
T	2
or	0
alpha	1
-	2
TAc	2
increases	0
membrane	0
packing	0
and	0
prevents	0
TAM	1
partition	0
into	0
model	0
membranes	0
.	0
These	0
effects	0
suggest	0
that	0
the	0
protection	0
from	0
hemolysis	3
by	0
tocopherols	1
is	0
related	0
to	0
a	0
decreased	0
TAM	1
incorporation	0
in	0
condensed	0
membranes	0
and	0
the	0
structural	0
damage	0
of	0
the	0
erythrocyte	0
membrane	0
is	0
consequently	0
avoided	0
.	0
Therefore	0
","	0
TAM	1
-	0
induced	0
hemolysis	3
results	0
from	0
a	0
structural	0
perturbation	0
of	0
red	0
cell	0
membrane	0
","	0
leading	0
to	0
changes	0
in	0
the	0
framework	0
of	0
the	0
erythrocyte	0
membrane	0
and	0
its	0
cytoskeleton	0
caused	0
by	0
its	0
high	0
partition	0
in	0
the	0
membrane	0
.	0
These	0
defects	0
explain	0
the	0
abnormal	0
erythrocyte	0
shape	0
and	0
decreased	0
mechanical	0
stability	0
promoted	0
by	0
TAM	1
","	0
resulting	0
in	0
hemolytic	3
anemia	4
.	0
Additionally	0
","	0
since	0
membrane	0
leakage	0
is	0
a	0
final	0
stage	0
of	0
cytotoxicity	0
","	0
the	0
disruption	0
of	0
the	0
structural	0
characteristics	0
of	0
biomembranes	0
by	0
TAM	1
may	0
contribute	0
to	0
the	0
multiple	0
mechanisms	0
of	0
its	0
anticancer	0
action	0
.	0
Changes	0
of	0
sodium	1
and	0
ATP	1
affinities	0
of	0
the	0
cardiac	0
(	0
Na	1
","	0
K	1
)	0
-	0
ATPase	0
during	0
and	0
after	0
nitric	1
oxide	2
deficient	0
hypertension	3
.	0
In	0
the	0
cardiovascular	0
system	0
","	0
N0	1
is	0
involved	0
in	0
the	0
regulation	0
of	0
a	0
variety	0
of	0
functions	0
.	0
Inhibition	0
of	0
N0	1
synthesis	0
induces	0
sustained	0
hypertension	3
.	0
In	0
several	0
models	0
of	0
hypertension	3
","	0
elevation	0
of	0
intracellular	0
sodium	1
level	0
was	0
documented	0
in	0
cardiac	0
tissue	0
.	0
To	0
assess	0
the	0
molecular	0
basis	0
of	0
disturbances	0
in	0
transmembraneous	0
transport	0
of	0
Na	1
+	0
","	0
we	0
studied	0
the	0
response	0
of	0
cardiac	0
(	0
Na	1
","	0
K	1
)	0
-	0
ATPase	0
to	0
N0	1
-	0
deficient	0
hypertension	3
induced	0
in	0
rats	0
by	0
N0	1
-	0
synthase	0
inhibition	0
with	0
40	0
mg	0
/	0
kg	0
/	0
day	0
N	1
(	2
G	2
)	2
-	2
nitro	2
-	2
L	2
-	2
arginine	2
methyl	2
ester	2
(	0
L	1
-	2
NAME	2
)	0
for	0
4	0
four	0
weeks	0
.	0
After	0
4	0
-	0
week	0
administration	0
of	0
L	1
-	2
NAME	2
","	0
the	0
systolic	0
blood	0
pressure	0
(	0
SBP	0
)	0
increased	0
by	0
36	0
%	0
.	0
Two	0
weeks	0
after	0
terminating	0
the	0
treatment	0
","	0
the	0
SBP	0
recovered	0
to	0
control	0
value	0
.	0
When	0
activating	0
the	0
(	0
Na	1
","	0
K	1
)	0
-	0
ATPase	0
with	0
its	0
substrate	0
ATP	1
","	0
no	0
changes	0
in	0
Km	0
and	0
Vmax	0
values	0
were	0
observed	0
in	0
N0	1
-	0
deficient	0
rats	0
.	0
During	0
activation	0
with	0
Na	1
+	0
","	0
the	0
Vmax	0
remained	0
unchanged	0
","	0
however	0
the	0
K	1
(	0
Na	1
)	0
increased	0
by	0
50	0
%	0
","	0
indicating	0
a	0
profound	0
decrease	0
in	0
the	0
affinity	0
of	0
the	0
Na	1
+	0
-	0
binding	0
site	0
in	0
N0	1
-	0
deficient	0
rats	0
.	0
After	0
recovery	0
from	0
hypertension	3
","	0
the	0
activity	0
of	0
(	0
Na	1
","	0
K	1
)	0
-	0
ATPase	0
increased	0
","	0
due	0
to	0
higher	0
affinity	0
of	0
the	0
ATP	1
-	0
binding	0
site	0
","	0
as	0
revealed	0
from	0
the	0
lowered	0
Km	0
value	0
for	0
ATP	1
.	0
The	0
K	1
(	0
Na	1
)	0
value	0
for	0
Na	1
+	0
returned	0
to	0
control	0
value	0
.	0
Inhibition	0
of	0
N0	1
-	0
synthase	0
induced	0
a	0
reversible	0
hypertension	3
accompanied	0
by	0
depressed	3
Na	1
+	0
-	0
extrusion	0
from	0
cardiac	0
cells	0
as	0
a	0
consequence	0
of	0
deteriorated	0
Na	1
+	0
-	0
binding	0
properties	0
of	0
the	0
(	0
Na	1
","	0
K	1
)	0
-	0
ATPase	0
.	0
After	0
recovery	0
of	0
blood	0
pressure	0
to	0
control	0
values	0
","	0
the	0
extrusion	0
of	0
Na	1
+	0
from	0
cardiac	0
cells	0
was	0
normalized	0
","	0
as	0
revealed	0
by	0
restoration	0
of	0
the	0
(	0
Na	1
","	0
K	1
)	0
-	0
ATPase	0
activity	0
.	0
Effects	0
of	0
long	0
-	0
term	0
pretreatment	0
with	0
isoproterenol	1
on	0
bromocriptine	1
-	0
induced	0
tachycardia	3
in	0
conscious	0
rats	0
.	0
It	0
has	0
been	0
shown	0
that	0
bromocriptine	1
-	0
induced	0
tachycardia	3
","	0
which	0
persisted	0
after	0
adrenalectomy	0
","	0
is	0
(	0
i	0
)	0
mediated	0
by	0
central	0
dopamine	1
D2	0
receptor	0
activation	0
and	0
(	0
ii	0
)	0
reduced	0
by	0
5	0
-	0
day	0
isoproterenol	1
pretreatment	0
","	0
supporting	0
therefore	0
the	0
hypothesis	0
that	0
this	0
effect	0
is	0
dependent	0
on	0
sympathetic	0
outflow	0
to	0
the	0
heart	0
.	0
This	0
study	0
was	0
conducted	0
to	0
examine	0
whether	0
prolonged	0
pretreatment	0
with	0
isoproterenol	1
could	0
abolish	0
bromocriptine	1
-	0
induced	0
tachycardia	3
in	0
conscious	0
rats	0
.	0
Isoproterenol	1
pretreatment	0
for	0
15	0
days	0
caused	0
cardiac	3
hypertrophy	4
without	0
affecting	0
baseline	0
blood	0
pressure	0
and	0
heart	0
rate	0
.	0
In	0
control	0
rats	0
","	0
intravenous	0
bromocriptine	1
(	0
150	0
microg	0
/	0
kg	0
)	0
induced	0
significant	0
hypotension	3
and	0
tachycardia	3
.	0
Bromocriptine	1
-	0
induced	0
hypotension	3
was	0
unaffected	0
by	0
isoproterenol	1
pretreatment	0
","	0
while	0
tachycardia	3
was	0
reversed	0
to	0
significant	0
bradycardia	3
","	0
an	0
effect	0
that	0
was	0
partly	0
reduced	0
by	0
i	0
.	0
v	0
.	0
domperidone	1
(	0
0	0
.	0
5	0
mg	0
/	0
kg	0
)	0
.	0
Neither	0
cardiac	0
vagal	0
nor	0
sympathetic	0
tone	0
was	0
altered	0
by	0
isoproterenol	1
pretreatment	0
.	0
In	0
isolated	0
perfused	0
heart	0
preparations	0
from	0
isoproterenol	1
-	0
pretreated	0
rats	0
","	0
the	0
isoproterenol	1
-	0
induced	0
maximal	0
increase	0
in	0
left	0
ventricular	0
systolic	0
pressure	0
was	0
significantly	0
reduced	0
","	0
compared	0
with	0
saline	0
-	0
pretreated	0
rats	0
(	0
the	0
EC50	0
of	0
the	0
isoproterenol	1
-	0
induced	0
increase	0
in	0
left	0
ventricular	0
systolic	0
pressure	0
was	0
enhanced	0
approximately	0
22	0
-	0
fold	0
)	0
.	0
These	0
results	0
show	0
that	0
15	0
-	0
day	0
isoproterenol	1
pretreatment	0
not	0
only	0
abolished	0
but	0
reversed	0
bromocriptine	1
-	0
induced	0
tachycardia	3
to	0
bradycardia	3
","	0
an	0
effect	0
that	0
is	0
mainly	0
related	0
to	0
further	0
cardiac	0
beta	0
-	0
adrenoceptor	0
desensitization	0
rather	0
than	0
to	0
impairment	0
of	0
autonomic	0
regulation	0
of	0
the	0
heart	0
.	0
They	0
suggest	0
that	0
","	0
in	0
normal	0
conscious	0
rats	0
","	0
the	0
central	0
tachycardia	3
of	0
bromocriptine	1
appears	0
to	0
predominate	0
and	0
to	0
mask	0
the	0
bradycardia	3
of	0
this	0
agonist	0
at	0
peripheral	0
dopamine	1
D2	0
receptors	0
.	0
A	0
developmental	0
analysis	0
of	0
clonidine	1
'	0
s	0
effects	0
on	0
cardiac	0
rate	0
and	0
ultrasound	0
production	0
in	0
infant	0
rats	0
.	0
Under	0
controlled	0
conditions	0
","	0
infant	0
rats	0
emit	0
ultrasonic	0
vocalizations	0
during	0
extreme	0
cold	0
exposure	0
and	0
after	0
administration	0
of	0
the	0
alpha	0
(	0
2	0
)	0
adrenoceptor	0
agonist	0
","	0
clonidine	1
.	0
Previous	0
investigations	0
have	0
determined	0
that	0
","	0
in	0
response	0
to	0
clonidine	1
","	0
ultrasound	0
production	0
increases	0
through	0
the	0
2nd	0
-	0
week	0
postpartum	0
and	0
decreases	0
thereafter	0
.	0
Given	0
that	0
sympathetic	0
neural	0
dominance	0
exhibits	0
a	0
similar	0
developmental	0
pattern	0
","	0
and	0
given	0
that	0
clonidine	1
induces	0
sympathetic	0
withdrawal	0
and	0
bradycardia	3
","	0
we	0
hypothesized	0
that	0
clonidine	1
'	0
s	0
developmental	0
effects	0
on	0
cardiac	0
rate	0
and	0
ultrasound	0
production	0
would	0
mirror	0
each	0
other	0
.	0
Therefore	0
","	0
in	0
the	0
present	0
experiment	0
","	0
the	0
effects	0
of	0
clonidine	1
administration	0
(	0
0	0
.	0
5	0
mg	0
/	0
kg	0
)	0
on	0
cardiac	0
rate	0
and	0
ultrasound	0
production	0
were	0
examined	0
in	0
2	0
-	0
","	0
8	0
-	0
","	0
15	0
-	0
","	0
and	0
20	0
-	0
day	0
-	0
old	0
rats	0
.	0
Age	0
-	0
related	0
changes	0
in	0
ultrasound	0
production	0
corresponded	0
with	0
changes	0
in	0
cardiovascular	0
variables	0
","	0
including	0
baseline	0
cardiac	0
rate	0
and	0
clonidine	1
-	0
induced	0
bradycardia	3
.	0
This	0
experiment	0
is	0
discussed	0
with	0
regard	0
to	0
the	0
hypothesis	0
that	0
ultrasound	0
production	0
is	0
the	0
acoustic	0
by	0
-	0
product	0
of	0
a	0
physiological	0
maneuver	0
that	0
compensates	0
for	0
clonidine	1
'	0
s	0
detrimental	0
effects	0
on	0
cardiovascular	0
function	0
.	0
Recurrent	0
use	0
of	0
newer	0
oral	1
contraceptives	2
and	0
the	0
risk	0
of	0
venous	3
thromboembolism	4
.	0
The	0
epidemiological	0
studies	0
that	0
assessed	0
the	0
risk	0
of	0
venous	3
thromboembolism	4
(	0
VTE	3
)	0
associated	0
with	0
newer	0
oral	1
contraceptives	2
(	0
0C	1
)	0
did	0
not	0
distinguish	0
between	0
patterns	0
of	0
0C	1
use	0
","	0
namely	0
first	0
-	0
time	0
users	0
","	0
repeaters	0
and	0
switchers	0
.	0
Data	0
from	0
a	0
Transnational	0
case	0
-	0
control	0
study	0
were	0
used	0
to	0
assess	0
the	0
risk	0
of	0
VTE	3
for	0
the	0
latter	0
patterns	0
of	0
use	0
","	0
while	0
accounting	0
for	0
duration	0
of	0
use	0
.	0
0ver	0
the	0
period	0
1993	0
-	0
1996	0
","	0
551	0
cases	0
of	0
VTE	3
were	0
identified	0
in	0
Germany	0
and	0
the	0
UK	0
along	0
with	0
2066	0
controls	0
.	0
Totals	0
of	0
128	0
cases	0
and	0
650	0
controls	0
were	0
analysed	0
for	0
repeat	0
use	0
and	0
135	0
cases	0
and	0
622	0
controls	0
for	0
switching	0
patterns	0
.	0
The	0
adjusted	0
rate	0
ratio	0
of	0
VTE	3
for	0
repeat	0
users	0
of	0
third	0
generation	0
0C	1
was	0
0	0
.	0
6	0
(	0
95	0
%	0
CI	0
:	0
0	0
.	0
3	0
-	0
1	0
.	0
2	0
)	0
relative	0
to	0
repeat	0
users	0
of	0
second	0
generation	0
pills	0
","	0
whereas	0
it	0
was	0
1	0
.	0
3	0
(	0
95	0
%	0
CI	0
:	0
0	0
.	0
7	0
-	0
2	0
.	0
4	0
)	0
for	0
switchers	0
from	0
second	0
to	0
third	0
generation	0
pills	0
relative	0
to	0
switchers	0
from	0
third	0
to	0
second	0
generation	0
pills	0
.	0
We	0
conclude	0
that	0
second	0
and	0
third	0
generation	0
agents	0
are	0
associated	0
with	0
equivalent	0
risks	0
of	0
VTE	3
when	0
the	0
same	0
agent	0
is	0
used	0
repeatedly	0
after	0
interruption	0
periods	0
or	0
when	0
users	0
are	0
switched	0
between	0
the	0
two	0
generations	0
of	0
pills	0
.	0
These	0
analyses	0
suggest	0
that	0
the	0
higher	0
risk	0
observed	0
for	0
the	0
newer	0
0C	1
in	0
other	0
studies	0
may	0
be	0
the	0
result	0
of	0
inadequate	0
comparisons	0
of	0
pill	0
users	0
with	0
different	0
patterns	0
of	0
pill	0
use	0
.	0
Differential	0
effects	0
of	0
systemically	0
administered	0
ketamine	1
and	0
lidocaine	1
on	0
dynamic	0
and	0
static	0
hyperalgesia	3
induced	0
by	0
intradermal	0
capsaicin	1
in	0
humans	0
.	0
We	0
have	0
examined	0
the	0
effect	0
of	0
systemic	0
administration	0
of	0
ketamine	1
and	0
lidocaine	1
on	0
brush	0
-	0
evoked	0
(	0
dynamic	0
)	0
pain	3
and	0
punctate	0
-	0
evoked	0
(	0
static	0
)	0
hyperalgesia	3
induced	0
by	0
capsaicin	1
.	0
In	0
a	0
randomized	0
","	0
double	0
-	0
blind	0
","	0
placebo	0
-	0
controlled	0
","	0
crossover	0
study	0
","	0
we	0
studied	0
12	0
volunteers	0
in	0
three	0
experiments	0
.	0
Capsaicin	1
100	0
micrograms	0
was	0
injected	0
intradermally	0
on	0
the	0
volar	0
forearm	0
followed	0
by	0
an	0
i	0
.	0
v	0
.	0
infusion	0
of	0
ketamine	1
(	0
bolus	0
0	0
.	0
1	0
mg	0
kg	0
-	0
1	0
over	0
10	0
min	0
followed	0
by	0
infusion	0
of	0
7	0
micrograms	0
kg	0
-	0
1	0
min	0
-	0
1	0
)	0
","	0
lidocaine	1
5	0
mg	0
kg	0
-	0
1	0
or	0
saline	0
for	0
50	0
min	0
.	0
Infusion	0
started	0
15	0
min	0
after	0
injection	0
of	0
capsaicin	1
.	0
The	0
following	0
were	0
measured	0
:	0
spontaneous	0
pain	3
","	0
pain	3
evoked	0
by	0
punctate	0
and	0
brush	0
stimuli	0
(	0
VAS	0
)	0
","	0
and	0
areas	0
of	0
brush	0
-	0
evoked	0
and	0
punctate	0
-	0
evoked	0
hyperalgesia	3
.	0
Ketamine	1
reduced	0
both	0
the	0
area	0
of	0
brush	0
-	0
evoked	0
and	0
punctate	0
-	0
evoked	0
hyperalgesia	3
significantly	0
and	0
it	0
tended	0
to	0
reduce	0
brush	0
-	0
evoked	0
pain	3
.	0
Lidocaine	1
reduced	0
the	0
area	0
of	0
punctate	0
-	0
evoked	0
hyperalgesia	3
significantly	0
.	0
It	0
tended	0
to	0
reduce	0
VAS	0
scores	0
of	0
spontaneous	0
pain	3
but	0
had	0
no	0
effect	0
on	0
evoked	0
pain	3
.	0
The	0
differential	0
effects	0
of	0
ketamine	1
and	0
lidocaine	1
on	0
static	0
and	0
dynamic	0
hyperalgesia	3
suggest	0
that	0
the	0
two	0
types	0
of	0
hyperalgesia	3
are	0
mediated	0
by	0
separate	0
mechanisms	0
and	0
have	0
a	0
distinct	0
pharmacology	0
.	0
Development	0
of	0
apomorphine	1
-	0
induced	0
aggressive	3
behavior	4
:	0
comparison	0
of	0
adult	0
male	0
and	0
female	0
Wistar	0
rats	0
.	0
The	0
development	0
of	0
apomorphine	1
-	0
induced	0
(	0
1	0
.	0
0	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
once	0
daily	0
)	0
aggressive	3
behavior	4
of	0
adult	0
male	0
and	0
female	0
Wistar	0
rats	0
obtained	0
from	0
the	0
same	0
breeder	0
was	0
studied	0
in	0
two	0
consecutive	0
sets	0
.	0
In	0
male	0
animals	0
","	0
repeated	0
apomorphine	1
treatment	0
induced	0
a	0
gradual	0
development	0
of	0
aggressive	3
behavior	4
as	0
evidenced	0
by	0
the	0
increased	0
intensity	0
of	0
aggressiveness	3
and	0
shortened	0
latency	0
before	0
the	0
first	0
attack	0
toward	0
the	0
opponent	0
.	0
In	0
female	0
rats	0
","	0
only	0
a	0
weak	0
tendency	0
toward	0
aggressiveness	3
was	0
found	0
.	0
In	0
conclusion	0
","	0
the	0
present	0
study	0
demonstrates	0
gender	0
differences	0
in	0
the	0
development	0
of	0
the	0
apomorphine	1
-	0
induced	0
aggressive	3
behavior	4
and	0
indicates	0
that	0
the	0
female	0
rats	0
do	0
not	0
fill	0
the	0
validation	0
criteria	0
for	0
use	0
in	0
this	0
method	0
.	0
Intracranial	3
aneurysms	4
and	0
cocaine	3
abuse	4
:	0
analysis	0
of	0
prognostic	0
indicators	0
.	0
0BJECTIVE	0
:	0
The	0
outcome	0
of	0
subarachnoid	3
hemorrhage	4
associated	0
with	0
cocaine	3
abuse	4
is	0
reportedly	0
poor	0
.	0
However	0
","	0
no	0
study	0
in	0
the	0
literature	0
has	0
reported	0
the	0
use	0
of	0
a	0
statistical	0
model	0
to	0
analyze	0
the	0
variables	0
that	0
influence	0
outcome	0
.	0
METH0DS	0
:	0
A	0
review	0
of	0
admissions	0
during	0
a	0
6	0
-	0
year	0
period	0
revealed	0
14	0
patients	0
with	0
cocaine	1
-	0
related	0
aneurysms	3
.	0
This	0
group	0
was	0
compared	0
with	0
a	0
control	0
group	0
of	0
135	0
patients	0
with	0
ruptured	3
aneurysms	4
and	0
no	0
history	0
of	0
cocaine	3
abuse	4
.	0
Age	0
at	0
presentation	0
","	0
time	0
of	0
ictus	0
after	0
intoxication	0
","	0
Hunt	0
and	0
Hess	0
grade	0
of	0
subarachnoid	3
hemorrhage	4
","	0
size	0
of	0
the	0
aneurysm	3
","	0
location	0
of	0
the	0
aneurysm	3
","	0
and	0
the	0
Glasgow	0
0utcome	0
Scale	0
score	0
were	0
assessed	0
and	0
compared	0
.	0
RESULTS	0
:	0
The	0
patients	0
in	0
the	0
study	0
group	0
were	0
significantly	0
younger	0
than	0
the	0
patients	0
in	0
the	0
control	0
group	0
(	0
P	0
<	0
0	0
.	0
2	0
)	0
.	0
In	0
patients	0
in	0
the	0
study	0
group	0
","	0
all	0
aneurysms	3
were	0
located	0
in	0
the	0
anterior	0
circulation	0
.	0
The	0
majority	0
of	0
these	0
aneurysms	3
were	0
smaller	0
than	0
those	0
of	0
the	0
control	0
group	0
(	0
8	0
+	0
/	0
-	0
6	0
.	0
8	0
mm	0
versus	0
11	0
+	0
/	0
-	0
5	0
.	0
4	0
mm	0
;	0
P	0
=	0
0	0
.	0
5	0
)	0
.	0
The	0
differences	0
in	0
mortality	0
and	0
morbidity	0
between	0
the	0
two	0
groups	0
were	0
not	0
significant	0
.	0
Hunt	0
and	0
Hess	0
grade	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
and	0
age	0
(	0
P	0
<	0
0	0
.	0
7	0
)	0
were	0
significant	0
predictors	0
of	0
outcome	0
for	0
the	0
patients	0
with	0
cocaine	1
-	0
related	0
aneurysms	3
.	0
C0NCLUSI0N	0
:	0
Cocaine	1
use	0
predisposed	0
aneurysmal	3
rupture	4
at	0
a	0
significantly	0
earlier	0
age	0
and	0
in	0
much	0
smaller	0
aneurysms	3
.	0
Contrary	0
to	0
the	0
published	0
literature	0
","	0
this	0
group	0
did	0
reasonably	0
well	0
with	0
aggressive	0
management	0
.	0
Effect	0
of	0
intravenous	0
nimodipine	1
on	0
blood	0
pressure	0
and	0
outcome	0
after	0
acute	3
stroke	4
.	0
BACKGR0UND	0
AND	0
PURP0SE	0
:	0
The	0
Intravenous	0
Nimodipine	1
West	0
European	0
Stroke	3
Trial	0
(	0
INWEST	0
)	0
found	0
a	0
correlation	0
between	0
nimodipine	1
-	0
induced	0
reduction	3
in	4
blood	4
pressure	4
(	0
BP	0
)	0
and	0
an	0
unfavorable	0
outcome	0
in	0
acute	3
stroke	4
.	0
We	0
sought	0
to	0
confirm	0
this	0
correlation	0
with	0
and	0
without	0
adjustment	0
for	0
prognostic	0
variables	0
and	0
to	0
investigate	0
outcome	0
in	0
subgroups	0
with	0
increasing	0
levels	0
of	0
BP	3
reduction	4
.	0
METH0DS	0
:	0
Patients	0
with	0
a	0
clinical	0
diagnosis	0
of	0
ischemic	3
stroke	4
(	0
within	0
24	0
hours	0
)	0
were	0
consecutively	0
allocated	0
to	0
receive	0
placebo	0
(	0
n	0
=	0
100	0
)	0
","	0
1	0
mg	0
/	0
h	0
(	0
low	0
-	0
dose	0
)	0
nimodipine	1
(	0
n	0
=	0
101	0
)	0
","	0
or	0
2	0
mg	0
/	0
h	0
(	0
high	0
-	0
dose	0
)	0
nimodipine	1
(	0
n	0
=	0
94	0
)	0
.	0
The	0
correlation	0
between	0
average	0
BP	0
change	0
during	0
the	0
first	0
2	0
days	0
and	0
the	0
outcome	0
at	0
day	0
21	0
was	0
analyzed	0
.	0
RESULTS	0
:	0
Two	0
hundred	0
sixty	0
-	0
five	0
patients	0
were	0
included	0
in	0
this	0
analysis	0
(	0
n	0
=	0
92	0
","	0
93	0
","	0
and	0
80	0
for	0
placebo	0
","	0
low	0
dose	0
","	0
and	0
high	0
dose	0
","	0
respectively	0
)	0
.	0
Nimodipine	1
treatment	0
resulted	0
in	0
a	0
statistically	0
significant	0
reduction	3
in	4
systolic	4
BP	4
(	0
SBP	0
)	0
and	0
diastolic	0
BP	0
(	0
DBP	0
)	0
from	0
baseline	0
compared	0
with	0
placebo	0
during	0
the	0
first	0
few	0
days	0
.	0
In	0
multivariate	0
analysis	0
","	0
a	0
significant	0
correlation	0
between	0
DBP	3
reduction	4
and	0
worsening	0
of	0
the	0
neurological	0
score	0
was	0
found	0
for	0
the	0
high	0
-	0
dose	0
group	0
(	0
beta	0
=	0
0	0
.	0
49	0
","	0
P	0
=	0
0	0
.	0
48	0
)	0
.	0
Patients	0
with	0
a	0
DBP	3
reduction	4
of	0
>	0
or	0
=	0
20	0
%	0
in	0
the	0
high	0
-	0
dose	0
group	0
had	0
a	0
significantly	0
increased	0
adjusted	0
0R	0
for	0
the	0
compound	0
outcome	0
variable	0
death	3
or	0
dependency	0
(	0
Barthel	0
Index	0
<	0
60	0
)	0
(	0
n	0
/	0
N	0
=	0
25	0
/	0
26	0
","	0
0R	0
10	0
.	0
16	0
","	0
95	0
%	0
CI	0
1	0
.	0
2	0
to	0
101	0
.	0
74	0
)	0
and	0
death	3
alone	0
(	0
n	0
/	0
N	0
=	0
9	0
/	0
26	0
","	0
0R	0
4	0
.	0
336	0
","	0
95	0
%	0
CI	0
1	0
.	0
131	0
16	0
.	0
619	0
)	0
compared	0
with	0
all	0
placebo	0
patients	0
(	0
n	0
/	0
N	0
=	0
62	0
/	0
92	0
and	0
14	0
/	0
92	0
","	0
respectively	0
)	0
.	0
There	0
was	0
no	0
correlation	0
between	0
SBP	0
change	0
and	0
outcome	0
.	0
C0NCLUSI0NS	0
:	0
DBP	0
","	0
but	0
not	0
SBP	0
","	0
reduction	0
was	0
associated	0
with	0
neurological	0
worsening	0
after	0
the	0
intravenous	0
administration	0
of	0
high	0
-	0
dose	0
nimodipine	1
after	0
acute	3
stroke	4
.	0
For	0
low	0
-	0
dose	0
nimodipine	1
","	0
the	0
results	0
were	0
not	0
conclusive	0
.	0
These	0
results	0
do	0
not	0
confirm	0
or	0
exclude	0
a	0
neuroprotective	0
property	0
of	0
nimodipine	1
.	0
Neonatal	0
pyridoxine	1
responsive	0
convulsions	3
due	0
to	0
isoniazid	1
therapy	0
.	0
A	0
17	0
-	0
day	0
-	0
old	0
infant	0
on	0
isoniazid	1
therapy	0
13	0
mg	0
/	0
kg	0
daily	0
from	0
birth	0
because	0
of	0
maternal	0
tuberculosis	3
was	0
admitted	0
after	0
4	0
days	0
of	0
clonic	3
fits	4
.	0
No	0
underlying	0
infective	0
or	0
biochemical	0
cause	0
could	0
be	0
found	0
.	0
The	0
fits	3
ceased	0
within	0
4	0
hours	0
of	0
administering	0
intramuscular	0
pyridoxine	1
","	0
suggesting	0
an	0
aetiology	0
of	0
pyridoxine	1
deficiency	0
secondary	0
to	0
isoniazid	1
medication	0
.	0
Ketamine	1
sedation	0
for	0
the	0
reduction	0
of	0
children	0
'	0
s	0
fractures	3
in	0
the	0
emergency	0
department	0
.	0
BACKGR0UND	0
:	0
There	0
recently	0
has	0
been	0
a	0
resurgence	0
in	0
the	0
utilization	0
of	0
ketamine	1
","	0
a	0
unique	0
anesthetic	0
","	0
for	0
emergency	0
-	0
department	0
procedures	0
requiring	0
sedation	0
.	0
The	0
purpose	0
of	0
the	0
present	0
study	0
was	0
to	0
examine	0
the	0
safety	0
and	0
efficacy	0
of	0
ketamine	1
for	0
sedation	0
in	0
the	0
treatment	0
of	0
children	0
'	0
s	0
fractures	3
in	0
the	0
emergency	0
department	0
.	0
METH0DS	0
:	0
0ne	0
hundred	0
and	0
fourteen	0
children	0
(	0
average	0
age	0
","	0
5	0
.	0
3	0
years	0
;	0
range	0
","	0
twelve	0
months	0
to	0
ten	0
years	0
and	0
ten	0
months	0
)	0
who	0
underwent	0
closed	0
reduction	0
of	0
an	0
isolated	0
fracture	3
or	0
dislocation	3
in	0
the	0
emergency	0
department	0
at	0
a	0
level	0
-	0
I	0
trauma	3
center	0
were	0
prospectively	0
evaluated	0
.	0
Ketamine	1
hydrochloride	2
was	0
administered	0
intravenously	0
(	0
at	0
a	0
dose	0
of	0
two	0
milligrams	0
per	0
kilogram	0
of	0
body	0
weight	0
)	0
in	0
ninety	0
-	0
nine	0
of	0
the	0
patients	0
and	0
intramuscularly	0
(	0
at	0
a	0
dose	0
of	0
four	0
milligrams	0
per	0
kilogram	0
of	0
body	0
weight	0
)	0
in	0
the	0
other	0
fifteen	0
.	0
A	0
board	0
-	0
certified	0
emergency	0
physician	0
skilled	0
in	0
airway	0
management	0
supervised	0
administration	0
of	0
the	0
anesthetic	0
","	0
and	0
the	0
patients	0
were	0
monitored	0
by	0
a	0
registered	0
nurse	0
.	0
Any	0
pain	3
during	0
the	0
reduction	0
was	0
rated	0
by	0
the	0
orthopaedic	0
surgeon	0
treating	0
the	0
patient	0
according	0
to	0
the	0
Children	0
'	0
s	0
Hospital	0
of	0
Eastern	0
0ntario	0
Pain	3
Scale	0
(	0
CHE0PS	0
)	0
.	0
RESULTS	0
:	0
The	0
average	0
time	0
from	0
intravenous	0
administration	0
of	0
ketamine	1
to	0
manipulation	0
of	0
the	0
fracture	3
or	0
dislocation	3
was	0
one	0
minute	0
and	0
thirty	0
-	0
six	0
seconds	0
(	0
range	0
","	0
twenty	0
seconds	0
to	0
five	0
minutes	0
)	0
","	0
and	0
the	0
average	0
time	0
from	0
intramuscular	0
administration	0
to	0
manipulation	0
was	0
four	0
minutes	0
and	0
forty	0
-	0
two	0
seconds	0
(	0
range	0
","	0
sixty	0
seconds	0
to	0
fifteen	0
minutes	0
)	0
.	0
The	0
average	0
score	0
according	0
to	0
the	0
Children	0
'	0
s	0
Hospital	0
of	0
Eastern	0
0ntario	0
Pain	3
Scale	0
was	0
6	0
.	0
4	0
points	0
(	0
range	0
","	0
5	0
to	0
10	0
points	0
)	0
","	0
reflecting	0
minimal	0
or	0
no	0
pain	3
during	0
fracture	3
reduction	0
.	0
Adequate	0
fracture	3
reduction	0
was	0
obtained	0
in	0
111	0
of	0
the	0
children	0
.	0
Ninety	0
-	0
nine	0
percent	0
(	0
sixty	0
-	0
eight	0
)	0
of	0
the	0
sixty	0
-	0
nine	0
parents	0
present	0
during	0
the	0
reduction	0
were	0
pleased	0
with	0
the	0
sedation	0
and	0
would	0
allow	0
it	0
to	0
be	0
used	0
again	0
in	0
a	0
similar	0
situation	0
.	0
Patency	0
of	0
the	0
airway	0
and	0
independent	0
respiration	0
were	0
maintained	0
in	0
all	0
of	0
the	0
patients	0
.	0
Blood	0
pressure	0
and	0
heart	0
rate	0
remained	0
stable	0
.	0
Minor	0
side	0
effects	0
included	0
nausea	3
(	0
thirteen	0
patients	0
)	0
","	0
emesis	3
(	0
eight	0
of	0
the	0
thirteen	0
patients	0
with	0
nausea	3
)	0
","	0
clumsiness	3
(	0
evident	0
as	0
ataxic	3
movements	4
in	0
ten	0
patients	0
)	0
","	0
and	0
dysphoric	3
reaction	4
(	0
one	0
patient	0
)	0
.	0
No	0
long	0
-	0
term	0
sequelae	0
were	0
noted	0
","	0
and	0
no	0
patients	0
had	0
hallucinations	3
or	0
nightmares	0
.	0
C0NCLUSI0NS	0
:	0
Ketamine	1
reliably	0
","	0
safely	0
","	0
and	0
quickly	0
provided	0
adequate	0
sedation	0
to	0
effectively	0
facilitate	0
the	0
reduction	0
of	0
children	0
'	0
s	0
fractures	3
in	0
the	0
emergency	0
department	0
at	0
our	0
institution	0
.	0
Ketamine	1
should	0
only	0
be	0
used	0
in	0
an	0
environment	0
such	0
as	0
the	0
emergency	0
department	0
","	0
where	0
proper	0
one	0
-	0
on	0
-	0
one	0
monitoring	0
is	0
used	0
and	0
board	0
-	0
certified	0
physicians	0
skilled	0
in	0
airway	0
management	0
are	0
directly	0
involved	0
in	0
the	0
care	0
of	0
the	0
patient	0
.	0
Cyclosporine	1
and	0
tacrolimus	1
-	0
associated	0
thrombotic	3
microangiopathy	4
.	0
The	0
development	0
of	0
thrombotic	3
microangiopathy	4
(	0
TMA	3
)	0
associated	0
with	0
the	0
use	0
of	0
cyclosporine	1
has	0
been	0
well	0
documented	0
.	0
Treatments	0
have	0
included	0
discontinuation	0
or	0
reduction	0
of	0
cyclosporine	1
dose	0
with	0
or	0
without	0
concurrent	0
plasma	0
exchange	0
","	0
plasma	0
infusion	0
","	0
anticoagulation	0
","	0
and	0
intravenous	0
immunoglobulin	0
G	0
infusion	0
.	0
However	0
","	0
for	0
recipients	0
of	0
organ	0
transplantation	0
","	0
removing	0
the	0
inciting	0
agent	0
is	0
not	0
without	0
the	0
attendant	0
risk	0
of	0
precipitating	0
acute	0
rejection	0
and	0
graft	0
loss	0
.	0
The	0
last	0
decade	0
has	0
seen	0
the	0
emergence	0
of	0
tacrolimus	1
as	0
a	0
potent	0
immunosuppressive	0
agent	0
with	0
mechanisms	0
of	0
action	0
virtually	0
identical	0
to	0
those	0
of	0
cyclosporine	1
.	0
As	0
a	0
result	0
","	0
switching	0
to	0
tacrolimus	1
has	0
been	0
reported	0
to	0
be	0
a	0
viable	0
therapeutic	0
option	0
in	0
the	0
setting	0
of	0
cyclosporine	1
-	0
induced	0
TMA	3
.	0
With	0
the	0
more	0
widespread	0
application	0
of	0
tacrolimus	1
in	0
organ	0
transplantation	0
","	0
tacrolimus	1
-	0
associated	0
TMA	3
has	0
also	0
been	0
recognized	0
.	0
However	0
","	0
literature	0
regarding	0
the	0
incidence	0
of	0
the	0
recurrence	0
of	0
TMA	3
in	0
patients	0
exposed	0
sequentially	0
to	0
cyclosporine	1
and	0
tacrolimus	1
is	0
limited	0
.	0
We	0
report	0
a	0
case	0
of	0
a	0
living	0
donor	0
renal	0
transplant	0
recipient	0
who	0
developed	0
cyclosporine	1
-	0
induced	0
TMA	3
that	0
responded	0
to	0
the	0
withdrawal	0
of	0
cyclosporine	1
in	0
conjunction	0
with	0
plasmapheresis	0
and	0
fresh	0
frozen	0
plasma	0
replacement	0
therapy	0
.	0
Introduction	0
of	0
tacrolimus	1
as	0
an	0
alternative	0
immunosuppressive	0
agent	0
resulted	0
in	0
the	0
recurrence	0
of	0
TMA	3
and	0
the	0
subsequent	0
loss	0
of	0
the	0
renal	0
allograft	0
.	0
Patients	0
who	0
are	0
switched	0
from	0
cyclosporine	1
to	0
tacrolimus	1
or	0
vice	0
versa	0
should	0
be	0
closely	0
monitored	0
for	0
the	0
signs	0
and	0
symptoms	0
of	0
recurrent	0
TMA	3
.	0
Analgesic	0
effect	0
of	0
intravenous	0
ketamine	1
in	0
cancer	3
patients	0
on	0
morphine	1
therapy	0
:	0
a	0
randomized	0
","	0
controlled	0
","	0
double	0
-	0
blind	0
","	0
crossover	0
","	0
double	0
-	0
dose	0
study	0
.	0
Pain	3
not	0
responsive	0
to	0
morphine	1
is	0
often	0
problematic	0
.	0
Animal	0
and	0
clinical	0
studies	0
have	0
suggested	0
that	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
(	0
NMDA	1
)	0
antagonists	0
","	0
such	0
as	0
ketamine	1
","	0
may	0
be	0
effective	0
in	0
improving	0
opioid	0
analgesia	0
in	0
difficult	0
pain	3
syndromes	0
","	0
such	0
as	0
neuropathic	3
pain	4
.	0
A	0
slow	0
bolus	0
of	0
subhypnotic	0
doses	0
of	0
ketamine	1
(	0
0	0
.	0
25	0
mg	0
/	0
kg	0
or	0
0	0
.	0
50	0
mg	0
/	0
kg	0
)	0
was	0
given	0
to	0
10	0
cancer	3
patients	0
whose	0
pain	3
was	0
unrelieved	0
by	0
morphine	1
in	0
a	0
randomized	0
","	0
double	0
-	0
blind	0
","	0
crossover	0
","	0
double	0
-	0
dose	0
study	0
.	0
Pain	3
intensity	0
on	0
a	0
0	0
to	0
10	0
numerical	0
scale	0
;	0
nausea	3
and	0
vomiting	3
","	0
drowsiness	0
","	0
confusion	3
","	0
and	0
dry	3
mouth	4
","	0
using	0
a	0
scale	0
from	0
0	0
to	0
3	0
(	0
not	0
at	0
all	0
","	0
slight	0
","	0
a	0
lot	0
","	0
awful	0
)	0
;	0
Mini	0
-	0
Mental	0
State	0
Examination	0
(	0
MMSE	0
)	0
(	0
0	0
-	0
30	0
)	0
;	0
and	0
arterial	0
pressure	0
were	0
recorded	0
before	0
administration	0
of	0
drugs	0
(	0
T0	0
)	0
and	0
after	0
30	0
minutes	0
(	0
T30	0
)	0
","	0
60	0
minutes	0
(	0
T60	0
)	0
","	0
120	0
minutes	0
(	0
T120	0
)	0
","	0
and	0
180	0
minutes	0
(	0
T180	0
)	0
.	0
Ketamine	1
","	0
but	0
not	0
saline	0
solution	0
","	0
significantly	0
reduced	0
the	0
pain	3
intensity	0
in	0
almost	0
all	0
the	0
patients	0
at	0
both	0
doses	0
.	0
This	0
effect	0
was	0
more	0
relevant	0
in	0
patients	0
treated	0
with	0
higher	0
doses	0
.	0
Hallucinations	3
occurred	0
in	0
4	0
patients	0
","	0
and	0
an	0
unpleasant	0
sensation	0
(	0
"	0
empty	0
head	0
"	0
)	0
was	0
also	0
reported	0
by	0
2	0
patients	0
.	0
These	0
episodes	0
reversed	0
after	0
the	0
administration	0
of	0
diazepam	1
1	0
mg	0
intravenously	0
.	0
Significant	0
increases	0
in	0
drowsiness	0
were	0
reported	0
in	0
patients	0
treated	0
with	0
ketamine	1
in	0
both	0
groups	0
and	0
were	0
more	0
marked	0
with	0
ketamine	1
0	0
.	0
50	0
mg	0
/	0
kg	0
.	0
A	0
significant	0
difference	0
in	0
MMSE	0
was	0
observed	0
at	0
T30	0
in	0
patients	0
who	0
received	0
0	0
.	0
50	0
mg	0
/	0
kg	0
of	0
ketamine	1
.	0
Ketamine	1
can	0
improve	0
morphine	1
analgesia	0
in	0
difficult	0
pain	3
syndromes	0
","	0
such	0
as	0
neuropathic	3
pain	4
.	0
However	0
","	0
the	0
occurrence	0
of	0
central	0
adverse	0
effects	0
should	0
be	0
taken	0
into	0
account	0
","	0
especially	0
when	0
using	0
higher	0
doses	0
.	0
This	0
observation	0
should	0
be	0
tested	0
in	0
studies	0
of	0
prolonged	0
ketamine	1
administration	0
.	0
Paclitaxel	1
","	0
cisplatin	1
","	0
and	0
gemcitabine	1
combination	0
chemotherapy	0
within	0
a	0
multidisciplinary	0
therapeutic	0
approach	0
in	0
metastatic	0
nonsmall	3
cell	4
lung	4
carcinoma	4
.	0
BACKGR0UND	0
:	0
Cisplatin	1
-	0
based	0
chemotherapy	0
combinations	0
improve	0
quality	0
of	0
life	0
and	0
survival	0
in	0
advanced	0
nonsmall	3
cell	4
lung	4
carcinoma	4
(	0
NSCLC	3
)	0
.	0
The	0
emergence	0
of	0
new	0
active	0
drugs	0
might	0
translate	0
into	0
more	0
effective	0
regimens	0
for	0
the	0
treatment	0
of	0
this	0
disease	0
.	0
METH0DS	0
:	0
The	0
objective	0
of	0
this	0
study	0
was	0
to	0
determine	0
the	0
feasibility	0
","	0
response	0
rate	0
","	0
and	0
toxicity	3
of	0
a	0
paclitaxel	1
","	0
cisplatin	1
","	0
and	0
gemcitabine	1
combination	0
to	0
treat	0
metastatic	0
NSCLC	3
.	0
Thirty	0
-	0
five	0
consecutive	0
chemotherapy	0
-	0
naive	0
patients	0
with	0
Stage	0
IV	0
NSCLC	3
and	0
an	0
Eastern	0
Cooperative	0
0ncology	0
Group	0
performance	0
status	0
of	0
0	0
-	0
2	0
were	0
treated	0
with	0
a	0
combination	0
of	0
paclitaxel	1
(	0
135	0
mg	0
/	0
m	0
(	0
2	0
)	0
given	0
intravenously	0
in	0
3	0
hours	0
)	0
on	0
Day	0
1	0
","	0
cisplatin	1
(	0
120	0
mg	0
/	0
m	0
(	0
2	0
)	0
given	0
intravenously	0
in	0
6	0
hours	0
)	0
on	0
Day	0
1	0
","	0
and	0
gemcitabine	1
(	0
800	0
mg	0
/	0
m	0
(	0
2	0
)	0
given	0
intravenously	0
in	0
30	0
minutes	0
)	0
on	0
Days	0
1	0
and	0
8	0
","	0
every	0
4	0
weeks	0
.	0
Although	0
responding	0
patients	0
were	0
scheduled	0
to	0
receive	0
consolidation	0
radiotherapy	0
and	0
24	0
patients	0
received	0
preplanned	0
second	0
-	0
line	0
chemotherapy	0
after	0
disease	0
progression	0
","	0
the	0
response	0
and	0
toxicity	3
rates	0
reported	0
refer	0
only	0
to	0
the	0
chemotherapy	0
regimen	0
given	0
.	0
RESULTS	0
:	0
All	0
the	0
patients	0
were	0
examined	0
for	0
toxicity	3
;	0
34	0
were	0
examinable	0
for	0
response	0
.	0
An	0
objective	0
response	0
was	0
observed	0
in	0
73	0
.	0
5	0
%	0
of	0
the	0
patients	0
(	0
95	0
%	0
confidence	0
interval	0
[	0
CI	0
]	0
","	0
55	0
.	0
6	0
-	0
87	0
.	0
1	0
%	0
)	0
","	0
including	0
4	0
complete	0
responses	0
(	0
11	0
.	0
7	0
%	0
)	0
.	0
According	0
to	0
intention	0
-	0
to	0
-	0
treat	0
","	0
the	0
overall	0
response	0
rate	0
was	0
71	0
.	0
4	0
%	0
(	0
95	0
%	0
CI	0
","	0
53	0
.	0
7	0
-	0
85	0
.	0
4	0
%	0
)	0
.	0
After	0
154	0
courses	0
of	0
therapy	0
","	0
the	0
median	0
dose	0
intensity	0
was	0
131	0
mg	0
/	0
m	0
(	0
2	0
)	0
for	0
paclitaxel	1
(	0
97	0
.	0
3	0
%	0
)	0
","	0
117	0
mg	0
/	0
m	0
(	0
2	0
)	0
for	0
cisplatin	1
(	0
97	0
.	0
3	0
%	0
)	0
","	0
and	0
1378	0
mg	0
/	0
m	0
(	0
2	0
)	0
for	0
gemcitabine	1
(	0
86	0
.	0
2	0
%	0
)	0
.	0
World	0
Health	0
0rganization	0
Grade	0
3	0
-	0
4	0
neutropenia	3
and	0
thrombocytopenia	3
occurred	0
in	0
39	0
.	0
9	0
%	0
and	0
11	0
.	0
4	0
%	0
of	0
patients	0
","	0
respectively	0
.	0
There	0
was	0
one	0
treatment	0
-	0
related	0
death	3
.	0
Nonhematologic	0
toxicities	3
were	0
mild	0
.	0
After	0
a	0
median	0
follow	0
-	0
up	0
of	0
22	0
months	0
","	0
the	0
median	0
progression	0
free	0
survival	0
rate	0
was	0
7	0
months	0
","	0
and	0
the	0
median	0
survival	0
time	0
was	0
16	0
months	0
.	0
C0NCLUSI0NS	0
:	0
The	0
combination	0
of	0
paclitaxel	1
","	0
cisplatin	1
","	0
and	0
gemcitabine	1
is	0
well	0
tolerated	0
and	0
shows	0
high	0
activity	0
in	0
metastatic	0
NSCLC	3
.	0
This	0
treatment	0
merits	0
further	0
comparison	0
with	0
other	0
cisplatin	1
-	0
based	0
regimens	0
.	0
Serotonergic	1
antidepressants	2
and	0
urinary	3
incontinence	4
.	0
Many	0
new	0
serotonergic	1
antidepressants	2
have	0
been	0
introduced	0
over	0
the	0
past	0
decade	0
.	0
Although	0
urinary	3
incontinence	4
is	0
listed	0
as	0
one	0
side	0
effect	0
of	0
these	0
drugs	0
in	0
their	0
package	0
inserts	0
there	0
is	0
only	0
one	0
report	0
in	0
the	0
literature	0
.	0
This	0
concerns	0
2	0
male	0
patients	0
who	0
experienced	0
incontinence	3
while	0
taking	0
venlafaxine	1
.	0
In	0
the	0
present	0
paper	0
the	0
authors	0
describe	0
2	0
female	0
patients	0
who	0
developed	0
incontinence	3
secondary	0
to	0
the	0
selective	0
serotonin	1
reuptake	0
inhibitors	0
paroxetine	1
and	0
sertraline	1
","	0
as	0
well	0
as	0
a	0
third	0
who	0
developed	0
this	0
side	0
effect	0
on	0
venlafaxine	1
.	0
In	0
2	0
of	0
the	0
3	0
cases	0
the	0
patients	0
were	0
also	0
taking	0
lithium	1
carbonate	2
and	0
beta	0
-	0
blockers	0
","	0
both	0
of	0
which	0
could	0
have	0
contributed	0
to	0
the	0
incontinence	3
.	0
Animal	0
studies	0
suggest	0
that	0
incontinence	3
secondary	0
to	0
serotonergic	1
antidepressants	2
could	0
be	0
mediated	0
by	0
the	0
5HT4	0
receptors	0
found	0
on	0
the	0
bladder	0
.	0
Further	0
research	0
is	0
needed	0
to	0
delineate	0
the	0
frequency	0
of	0
this	0
troubling	0
side	0
effect	0
and	0
how	0
best	0
to	0
treat	0
it	0
.	0
Acute	0
cocaine	1
-	0
induced	0
seizures	3
:	0
differential	0
sensitivity	0
of	0
six	0
inbred	0
mouse	0
strains	0
.	0
Mature	0
male	0
and	0
female	0
mice	0
from	0
six	0
inbred	0
stains	0
were	0
tested	0
for	0
susceptibility	0
to	0
behavioral	0
seizures	3
induced	0
by	0
a	0
single	0
injection	0
of	0
cocaine	1
.	0
Cocaine	1
was	0
injected	0
ip	0
over	0
a	0
range	0
of	0
doses	0
(	0
50	0
-	0
100	0
mg	0
/	0
kg	0
)	0
and	0
behavior	0
was	0
monitored	0
for	0
20	0
minutes	0
.	0
Seizure	3
end	0
points	0
included	0
latency	0
to	0
forelimb	0
or	0
hindlimb	0
clonus	0
","	0
latency	0
to	0
clonic	0
running	0
seizure	3
and	0
latency	0
to	0
jumping	0
bouncing	0
seizure	3
.	0
A	0
range	0
of	0
strain	0
specific	0
sensitivities	0
was	0
documented	0
with	0
A	0
/	0
J	0
and	0
SJL	0
mice	0
being	0
most	0
sensitive	0
and	0
C57BL	0
/	0
6J	0
most	0
resistant	0
.	0
DBA	0
/	0
2J	0
","	0
BALB	0
/	0
cByJ	0
and	0
NZW	0
/	0
LacJ	0
strains	0
exhibited	0
intermediate	0
sensitivity	0
.	0
EEG	0
recordings	0
were	0
made	0
in	0
SJL	0
","	0
A	0
/	0
J	0
and	0
C57BL	0
/	0
6J	0
mice	0
revealing	0
a	0
close	0
correspondence	0
between	0
electrical	0
activity	0
and	0
behavior	0
.	0
Additionally	0
","	0
levels	0
of	0
cocaine	1
determined	0
in	0
hippocampus	0
and	0
cortex	0
were	0
not	0
different	0
between	0
sensitive	0
and	0
resistant	0
strains	0
.	0
Additional	0
studies	0
of	0
these	0
murine	0
strains	0
may	0
be	0
useful	0
for	0
investigating	0
genetic	0
influences	0
on	0
cocaine	1
-	0
induced	0
seizures	3
.	0
Hypotension	3
following	0
the	0
initiation	0
of	0
tizanidine	1
in	0
a	0
patient	0
treated	0
with	0
an	0
angiotensin	1
converting	0
enzyme	0
inhibitor	0
for	0
chronic	0
hypertension	3
.	0
Centrally	0
acting	0
alpha	0
-	0
2	0
adrenergic	0
agonists	0
are	0
one	0
of	0
several	0
pharmacologic	0
agents	0
used	0
in	0
the	0
treatment	0
of	0
spasticity	3
related	0
to	0
disorders	3
of	4
the	4
central	4
nervous	4
system	4
.	0
In	0
addition	0
to	0
their	0
effects	0
on	0
spasticity	3
","	0
certain	0
adverse	0
cardiorespiratory	0
effects	0
have	0
been	0
reported	0
.	0
Adults	0
chronically	0
treated	0
with	0
angiotensin	1
converting	0
enzyme	0
inhibitors	0
may	0
have	0
a	0
limited	0
ability	0
to	0
respond	0
to	0
hypotension	3
when	0
the	0
sympathetic	0
response	0
is	0
simultaneously	0
blocked	0
.	0
The	0
authors	0
present	0
a	0
10	0
-	0
year	0
-	0
old	0
boy	0
chronically	0
treated	0
with	0
lisinopril	1
","	0
an	0
angiotensin	1
converting	0
enzyme	0
inhibitor	0
","	0
to	0
control	0
hypertension	3
who	0
developed	0
hypotension	3
following	0
the	0
addition	0
of	0
tizanidine	1
","	0
an	0
alpha	0
-	0
2	0
agonist	0
","	0
for	0
the	0
treatment	0
of	0
spasticity	3
.	0
The	0
possible	0
interaction	0
of	0
tizanidine	1
and	0
other	0
antihypertensive	0
agents	0
should	0
be	0
kept	0
in	0
mind	0
when	0
prescribing	0
therapy	0
to	0
treat	0
either	0
hypertension	3
or	0
spasticity	3
in	0
such	0
patients	0
.	0
Two	0
mouse	0
lines	0
selected	0
for	0
differential	0
sensitivities	0
to	0
beta	1
-	2
carboline	2
-	0
induced	0
seizures	3
are	0
also	0
differentially	0
sensitive	0
to	0
various	0
pharmacological	0
effects	0
of	0
other	0
GABA	1
(	0
A	0
)	0
receptor	0
ligands	0
.	0
Two	0
mouse	0
lines	0
were	0
selectively	0
bred	0
according	0
to	0
their	0
sensitivity	0
(	0
BS	0
line	0
)	0
or	0
resistance	0
(	0
BR	0
line	0
)	0
to	0
seizures	3
induced	0
by	0
a	0
single	0
i	0
.	0
p	0
.	0
injection	0
of	0
methyl	1
beta	2
-	2
carboline	2
-	2
3	2
-	2
carboxylate	2
(	0
beta	1
-	2
CCM	2
)	0
","	0
an	0
inverse	0
agonist	0
of	0
the	0
GABA	1
(	0
A	0
)	0
receptor	0
benzodiazepine	1
site	0
.	0
0ur	0
aim	0
was	0
to	0
characterize	0
both	0
lines	0
'	0
sensitivities	0
to	0
various	0
physiological	0
effects	0
of	0
other	0
ligands	0
of	0
the	0
GABA	1
(	0
A	0
)	0
receptor	0
.	0
We	0
measured	0
diazepam	1
-	0
induced	0
anxiolysis	0
with	0
the	0
elevated	0
plus	0
-	0
maze	0
test	0
","	0
diazepam	1
-	0
induced	0
sedation	0
by	0
recording	0
the	0
vigilance	0
states	0
","	0
and	0
picrotoxin	1
-	0
and	0
pentylenetetrazol	1
-	0
induced	0
seizures	3
after	0
i	0
.	0
p	0
.	0
injections	0
.	0
Results	0
presented	0
here	0
show	0
that	0
the	0
differential	0
sensitivities	0
of	0
BS	0
and	0
BR	0
lines	0
to	0
beta	1
-	2
CCM	2
can	0
be	0
extended	0
to	0
diazepam	1
","	0
picrotoxin	1
","	0
and	0
pentylenetetrazol	1
","	0
suggesting	0
a	0
genetic	0
selection	0
of	0
a	0
general	0
sensitivity	0
and	0
resistance	0
to	0
several	0
ligands	0
of	0
the	0
GABA	1
(	0
A	0
)	0
receptor	0
.	0
Propylthiouracil	1
-	0
induced	0
perinuclear	0
-	0
staining	0
antineutrophil	0
cytoplasmic	0
autoantibody	0
-	0
positive	0
vasculitis	3
in	0
conjunction	0
with	0
pericarditis	3
.	0
0BJECTIVE	0
:	0
To	0
describe	0
a	0
case	0
of	0
propylthiouracil	1
-	0
induced	0
vasculitis	3
manifesting	0
with	0
pericarditis	3
.	0
METH0DS	0
:	0
We	0
present	0
the	0
first	0
case	0
report	0
of	0
a	0
woman	0
with	0
hyperthyroidism	3
treated	0
with	0
propylthiouracil	1
in	0
whom	0
a	0
syndrome	0
of	0
pericarditis	3
","	0
fever	3
","	0
and	0
glomerulonephritis	3
developed	0
.	0
Serologic	0
testing	0
and	0
immunologic	0
studies	0
were	0
done	0
","	0
and	0
a	0
pericardial	0
biopsy	0
was	0
performed	0
.	0
RESULTS	0
:	0
A	0
25	0
-	0
year	0
-	0
old	0
woman	0
with	0
Graves	3
'	4
disease	4
had	0
a	0
febrile	3
illness	4
and	0
evidence	0
of	0
pericarditis	3
","	0
which	0
was	0
confirmed	0
by	0
biopsy	0
.	0
Serologic	0
evaluation	0
revealed	0
the	0
presence	0
of	0
perinuclear	0
-	0
staining	0
antineutrophil	0
cytoplasmic	0
autoantibodies	0
(	0
pANCA	0
)	0
against	0
myeloperoxidase	0
(	0
MP0	0
)	0
.	0
Propylthiouracil	1
therapy	0
was	0
withdrawn	0
","	0
and	0
she	0
was	0
treated	0
with	0
a	0
1	0
-	0
month	0
course	0
of	0
prednisone	1
","	0
which	0
alleviated	0
her	0
symptoms	0
.	0
A	0
literature	0
review	0
revealed	0
no	0
prior	0
reports	0
of	0
pericarditis	3
in	0
anti	0
-	0
MP0	0
pANCA	0
-	0
positive	0
vasculitis	3
associated	0
with	0
propylthio	1
-	2
uracil	2
therapy	0
.	0
C0NCLUSI0N	0
:	0
Pericarditis	3
may	0
be	0
the	0
initial	0
manifestation	0
of	0
drug	0
-	0
induced	0
vasculitis	3
attributable	0
to	0
propylthio	1
-	2
uracil	2
therapy	0
.	0
Repeated	0
transient	0
anuria	3
following	0
losartan	1
administration	0
in	0
a	0
patient	0
with	0
a	0
solitary	0
kidney	0
.	0
We	0
report	0
the	0
case	0
of	0
a	0
70	0
-	0
year	0
-	0
old	0
hypertensive	3
man	0
with	0
a	0
solitary	0
kidney	0
and	0
chronic	3
renal	4
insufficiency	4
who	0
developed	0
two	0
episodes	0
of	0
transient	0
anuria	3
after	0
losartan	1
administration	0
.	0
He	0
was	0
hospitalized	0
for	0
a	0
myocardial	3
infarction	4
with	0
pulmonary	3
edema	4
","	0
treated	0
with	0
high	0
-	0
dose	0
diuretics	0
.	0
Due	0
to	0
severe	0
systolic	3
dysfunction	4
losartan	1
was	0
prescribed	0
.	0
Surprisingly	0
","	0
the	0
first	0
dose	0
of	0
50	0
mg	0
of	0
losartan	1
resulted	0
in	0
a	0
sudden	0
anuria	3
","	0
which	0
lasted	0
eight	0
hours	0
despite	0
high	0
-	0
dose	0
furosemide	1
and	0
amine	1
infusion	0
.	0
0ne	0
week	0
later	0
","	0
by	0
mistake	0
","	0
losartan	1
was	0
prescribed	0
again	0
and	0
after	0
the	0
second	0
dose	0
of	0
50	0
mg	0
","	0
the	0
patient	0
developed	0
a	0
second	0
episode	0
of	0
transient	0
anuria	3
lasting	0
10	0
hours	0
.	0
During	0
these	0
two	0
episodes	0
","	0
his	0
blood	0
pressure	0
diminished	0
but	0
no	0
severe	0
hypotension	3
was	0
noted	0
.	0
Ultimately	0
","	0
an	0
arteriography	0
showed	0
a	0
70	0
-	0
80	0
%	0
renal	3
artery	4
stenosis	4
.	0
In	0
this	0
patient	0
","	0
renal	3
artery	4
stenosis	4
combined	0
with	0
heart	3
failure	4
and	0
diuretic	0
therapy	0
certainly	0
resulted	0
in	0
a	0
strong	0
activation	0
of	0
the	0
renin	0
-	0
angiotensin	1
system	0
(	0
RAS	0
)	0
.	0
Under	0
such	0
conditions	0
","	0
angiotensin	1
II	2
receptor	0
blockade	0
by	0
losartan	1
probably	0
induced	0
a	0
critical	0
fall	0
in	0
glomerular	0
filtration	0
pressure	0
.	0
This	0
case	0
report	0
highlights	0
the	0
fact	0
that	0
the	0
angiotensin	1
II	2
receptor	0
antagonist	0
losartan	1
can	0
cause	0
serious	0
unexpected	0
complications	0
in	0
patients	0
with	0
renovascular	3
disease	4
and	0
should	0
be	0
used	0
with	0
extreme	0
caution	0
in	0
this	0
setting	0
.	0
Calcineurin	0
-	0
inhibitor	0
induced	0
pain	3
syndrome	0
(	0
CIPS	3
)	0
:	0
a	0
severe	0
disabling	0
complication	0
after	0
organ	0
transplantation	0
.	0
Bone	0
pain	3
after	0
transplantation	0
is	0
a	0
frequent	0
complication	0
that	0
can	0
be	0
caused	0
by	0
several	0
diseases	0
.	0
Treatment	0
strategies	0
depend	0
on	0
the	0
correct	0
diagnosis	0
of	0
the	0
pain	3
.	0
Nine	0
patients	0
with	0
severe	0
pain	3
in	0
their	0
feet	0
","	0
which	0
was	0
registered	0
after	0
transplantation	0
","	0
were	0
investigated	0
.	0
Bone	0
scans	0
showed	0
an	0
increased	0
tracer	0
uptake	0
of	0
the	0
foot	0
bones	0
.	0
Magnetic	0
resonance	0
imaging	0
demonstrated	0
bone	3
marrow	4
oedema	4
in	0
the	0
painful	0
bones	0
.	0
Pain	3
was	0
not	0
explained	0
by	0
other	0
diseases	0
causing	0
foot	0
pain	3
","	0
like	0
reflex	3
sympathetic	4
dystrophy	4
","	0
polyneuropathy	3
","	0
Morton	3
'	4
s	4
neuralgia	4
","	0
gout	3
","	0
osteoporosis	3
","	0
avascular	3
necrosis	4
","	0
intermittent	3
claudication	4
","	0
orthopaedic	0
foot	3
deformities	4
","	0
stress	3
fractures	4
","	0
and	0
hyperparathyroidism	3
.	0
The	0
reduction	0
of	0
cyclosporine	1
-	0
or	0
tacrolimus	1
trough	0
levels	0
and	0
the	0
administration	0
of	0
calcium	1
channel	0
blockers	0
led	0
to	0
relief	0
of	0
pain	3
.	0
The	0
Calcineurin	0
-	0
inhibitor	0
Induced	0
Pain	3
Syndrome	0
(	0
CIPS	3
)	0
is	0
a	0
rare	0
but	0
severe	0
side	0
effect	0
of	0
cyclosporine	1
or	0
tacrolimus	1
and	0
is	0
accurately	0
diagnosed	0
by	0
its	0
typical	0
presentation	0
","	0
magnetic	0
resonance	0
imaging	0
and	0
bone	0
scans	0
.	0
Incorrect	0
diagnosis	0
of	0
the	0
syndrome	0
will	0
lead	0
to	0
a	0
significant	0
reduction	0
of	0
life	0
quality	0
in	0
patients	0
suffering	0
from	0
CIPS	3
.	0
Brain	0
natriuretic	0
peptide	0
is	0
a	0
predictor	0
of	0
anthracycline	1
-	0
induced	0
cardiotoxicity	3
.	0
Anthracyclines	1
are	0
effective	0
antineoplastic	0
drugs	0
","	0
but	0
they	0
frequently	0
cause	0
dose	0
-	0
related	0
cardiotoxicity	3
.	0
The	0
cardiotoxicity	3
of	0
conventional	0
anthracycline	1
therapy	0
highlights	0
a	0
need	0
to	0
search	0
for	0
methods	0
that	0
are	0
highly	0
sensitive	0
and	0
capable	0
of	0
predicting	0
cardiac	3
dysfunction	4
.	0
We	0
measured	0
the	0
plasma	0
level	0
of	0
brain	0
natriuretic	0
peptide	0
(	0
BNP	0
)	0
to	0
determine	0
whether	0
BNP	0
might	0
serve	0
as	0
a	0
simple	0
diagnostic	0
indicator	0
of	0
anthracycline	1
-	0
induced	0
cardiotoxicity	3
in	0
patients	0
with	0
acute	3
leukemia	4
treated	0
with	0
a	0
daunorubicin	1
(	0
DNR	1
)	0
-	0
containing	0
regimen	0
.	0
Thirteen	0
patients	0
with	0
acute	3
leukemia	4
were	0
treated	0
with	0
a	0
DNR	1
-	0
containing	0
regimen	0
.	0
Cardiac	0
functions	0
were	0
evaluated	0
with	0
radionuclide	0
angiography	0
before	0
chemotherapies	0
.	0
The	0
plasma	0
levels	0
of	0
atrial	0
natriuretic	0
peptide	0
(	0
ANP	0
)	0
and	0
BNP	0
were	0
measured	0
at	0
the	0
time	0
of	0
radionuclide	0
angiography	0
.	0
Three	0
patients	0
developed	0
congestive	3
heart	4
failure	4
after	0
the	0
completion	0
of	0
chemotherapy	0
.	0
Five	0
patients	0
were	0
diagnosed	0
as	0
having	0
subclinical	0
heart	3
failure	4
after	0
the	0
completion	0
of	0
chemotherapy	0
.	0
The	0
plasma	0
levels	0
of	0
BNP	0
in	0
all	0
the	0
patients	0
with	0
clinical	0
and	0
subclinical	0
heart	3
failure	4
increased	0
above	0
the	0
normal	0
limit	0
(	0
40	0
pg	0
/	0
ml	0
)	0
before	0
the	0
detection	0
of	0
clinical	0
or	0
subclinical	0
heart	3
failure	4
by	0
radionuclide	0
angiography	0
.	0
0n	0
the	0
other	0
hand	0
","	0
BNP	0
did	0
not	0
increase	0
in	0
the	0
patients	0
without	0
heart	3
failure	4
given	0
DNR	1
","	0
even	0
at	0
more	0
than	0
700	0
mg	0
/	0
m	0
(	0
2	0
)	0
.	0
The	0
plasma	0
level	0
of	0
ANP	0
did	0
not	0
always	0
increase	0
in	0
all	0
the	0
patients	0
with	0
clinical	0
and	0
subclinical	0
heart	3
failure	4
.	0
These	0
preliminary	0
results	0
suggest	0
that	0
BNP	0
may	0
be	0
useful	0
as	0
an	0
early	0
and	0
sensitive	0
indicator	0
of	0
anthracycline	1
-	0
induced	0
cardiotoxicity	3
.	0
Nephrotoxicity	3
of	0
combined	0
cephalothin	1
-	0
gentamicin	1
regimen	0
.	0
Two	0
patients	0
developed	0
acute	3
tubular	4
necrosis	4
","	0
characterized	0
clinically	0
by	0
acute	0
oliguric	3
renal	4
failure	4
","	0
while	0
they	0
were	0
receiving	0
a	0
combination	0
of	0
cephalothin	1
sodium	2
and	0
gentamicin	1
sulfate	2
therapy	0
.	0
Patients	0
who	0
are	0
given	0
this	0
drug	0
regimen	0
should	0
be	0
observed	0
very	0
carefully	0
for	0
early	0
signs	0
of	0
nephrotoxicity	3
.	0
High	0
doses	0
of	0
this	0
antibiotic	0
combination	0
should	0
be	0
avoided	0
especially	0
in	0
elderly	0
patients	0
.	0
Patients	0
with	0
renal	3
insufficiency	4
should	0
not	0
be	0
given	0
this	0
regimen	0
.	0
In	0
vivo	0
protection	0
of	0
dna	0
damage	0
associated	0
apoptotic	0
and	0
necrotic	3
cell	0
deaths	0
during	0
acetaminophen	1
-	0
induced	0
nephrotoxicity	3
","	0
amiodarone	1
-	0
induced	0
lung	3
toxicity	4
and	0
doxorubicin	1
-	0
induced	0
cardiotoxicity	3
by	0
a	0
novel	0
IH636	1
grape	2
seed	2
proanthocyanidin	2
extract	2
.	0
Grape	1
seed	2
extract	2
","	0
primarily	0
a	0
mixture	0
of	0
proanthocyanidins	1
","	0
has	0
been	0
shown	0
to	0
modulate	0
a	0
wide	0
-	0
range	0
of	0
biological	0
","	0
pharmacological	0
and	0
toxicological	0
effects	0
which	0
are	0
mainly	0
cytoprotective	0
.	0
This	0
study	0
assessed	0
the	0
ability	0
of	0
IH636	1
grape	2
seed	2
proanthocyanidin	2
extract	2
(	0
GSPE	1
)	0
to	0
prevent	0
acetaminophen	1
(	0
AAP	1
)	0
-	0
induced	0
nephrotoxicity	3
","	0
amiodarone	1
(	0
AMI	1
)	0
-	0
induced	0
lung	3
toxicity	4
","	0
and	0
doxorubicin	1
(	0
D0X	1
)	0
-	0
induced	0
cardiotoxicity	3
in	0
mice	0
.	0
Experimental	0
design	0
consisted	0
of	0
four	0
groups	0
:	0
control	0
(	0
vehicle	0
alone	0
)	0
","	0
GSPE	1
alone	0
","	0
drug	0
alone	0
and	0
GSPE	1
+	0
drug	0
.	0
For	0
the	0
cytoprotection	0
study	0
","	0
animals	0
were	0
orally	0
gavaged	0
100	0
mg	0
/	0
Kg	0
GSPE	1
for	0
7	0
-	0
10	0
days	0
followed	0
by	0
i	0
.	0
p	0
.	0
injections	0
of	0
organ	0
specific	0
three	0
drugs	0
(	0
AAP	1
:	0
500	0
mg	0
/	0
Kg	0
for	0
24	0
h	0
;	0
AMI	1
:	0
50	0
mg	0
/	0
Kg	0
/	0
day	0
for	0
four	0
days	0
;	0
D0X	1
:	0
20	0
mg	0
/	0
Kg	0
for	0
48	0
h	0
)	0
.	0
Parameters	0
of	0
study	0
included	0
analysis	0
of	0
serum	0
chemistry	0
(	0
ALT	0
","	0
BUN	0
and	0
CPK	0
)	0
","	0
and	0
orderly	0
fragmentation	0
of	0
genomic	0
DNA	0
(	0
both	0
endonuclease	0
-	0
dependent	0
and	0
independent	0
)	0
in	0
addition	0
to	0
microscopic	0
evaluation	0
of	0
damage	0
and	0
/	0
or	0
protection	0
in	0
corresponding	0
PAS	0
stained	0
tissues	0
.	0
Results	0
indicate	0
that	0
GSPE	1
preexposure	0
prior	0
to	0
AAP	1
","	0
AMI	1
and	0
D0X	1
","	0
provided	0
near	0
complete	0
protection	0
in	0
terms	0
of	0
serum	0
chemistry	0
changes	0
(	0
ALT	0
","	0
BUN	0
and	0
CPK	0
)	0
","	0
and	0
significantly	0
reduced	0
DNA	0
fragmentation	0
.	0
Histopathological	0
examination	0
of	0
kidney	0
","	0
heart	0
and	0
lung	0
sections	0
revealed	0
moderate	0
to	0
massive	0
tissue	3
damage	4
with	0
a	0
variety	0
of	0
morphological	0
aberrations	0
by	0
all	0
the	0
three	0
drugs	0
in	0
the	0
absence	0
of	0
GSPE	1
preexposure	0
than	0
in	0
its	0
presence	0
.	0
GSPE	1
+	0
drug	0
exposed	0
tissues	0
exhibited	0
minor	0
residual	0
damage	0
or	0
near	0
total	0
recovery	0
.	0
Additionally	0
","	0
histopathological	0
alterations	0
mirrored	0
both	0
serum	0
chemistry	0
changes	0
and	0
the	0
pattern	0
of	0
DNA	0
fragmentation	0
.	0
Interestingly	0
","	0
all	0
the	0
drugs	0
","	0
such	0
as	0
","	0
AAP	1
","	0
AMI	1
and	0
D0X	1
induced	0
apoptotic	0
death	0
in	0
addition	0
to	0
necrosis	3
in	0
the	0
respective	0
organs	0
which	0
was	0
very	0
effectively	0
blocked	0
by	0
GSPE	1
.	0
Since	0
AAP	1
","	0
AMI	1
and	0
D0X	1
undergo	0
biotransformation	0
and	0
are	0
known	0
to	0
produce	0
damaging	0
radicals	0
in	0
vivo	0
","	0
the	0
protection	0
by	0
GSPE	1
may	0
be	0
linked	0
to	0
both	0
inhibition	0
of	0
metabolism	0
and	0
/	0
or	0
detoxification	0
of	0
cytotoxic	0
radicals	0
.	0
In	0
addition	0
","	0
its	0
'	0
presumed	0
contribution	0
to	0
DNA	0
repair	0
may	0
be	0
another	0
important	0
attribute	0
","	0
which	0
played	0
a	0
role	0
in	0
the	0
chemoprevention	0
process	0
.	0
Additionally	0
","	0
this	0
may	0
have	0
been	0
the	0
first	0
report	0
on	0
AMI	1
-	0
induced	0
apoptotic	0
death	0
in	0
the	0
lung	0
tissue	0
.	0
Taken	0
together	0
","	0
these	0
events	0
undoubtedly	0
establish	0
GSPE	1
'	0
s	0
abundant	0
bioavailability	0
","	0
and	0
the	0
power	0
to	0
defend	0
multiple	0
target	0
organs	0
from	0
toxic	0
assaults	0
induced	0
by	0
structurally	0
diverse	0
and	0
functionally	0
different	0
entities	0
in	0
vivo	0
.	0
Antidepressant	1
-	0
induced	0
mania	3
in	0
bipolar	3
patients	0
:	0
identification	0
of	0
risk	0
factors	0
.	0
BACKGR0UND	0
:	0
Concerns	0
about	0
possible	0
risks	0
of	0
switching	0
to	0
mania	3
associated	0
with	0
antidepressants	1
continue	0
to	0
interfere	0
with	0
the	0
establishment	0
of	0
an	0
optimal	0
treatment	0
paradigm	0
for	0
bipolar	3
depression	4
.	0
METH0D	0
:	0
The	0
response	0
of	0
44	0
patients	0
meeting	0
DSM	0
-	0
IV	0
criteria	0
for	0
bipolar	3
disorder	4
to	0
naturalistic	0
treatment	0
was	0
assessed	0
for	0
at	0
least	0
6	0
weeks	0
using	0
the	0
Montgomery	0
-	0
Asberg	0
Depression	0
Rating	0
Scale	0
and	0
the	0
Bech	0
-	0
Rafaelson	0
Mania	0
Rating	0
Scale	0
.	0
Patients	0
who	0
experienced	0
a	0
manic	3
or	0
hypomanic	3
switch	0
were	0
compared	0
with	0
those	0
who	0
did	0
not	0
on	0
several	0
variables	0
including	0
age	0
","	0
sex	0
","	0
diagnosis	0
(	0
DSM	3
-	4
IV	4
bipolar	4
I	4
vs	0
.	0
bipolar	3
II	4
)	0
","	0
number	0
of	0
previous	0
manic	3
episodes	0
","	0
type	0
of	0
antidepressant	1
therapy	0
used	0
(	0
electroconvulsive	0
therapy	0
vs	0
.	0
antidepressant	1
drugs	0
and	0
","	0
more	0
particularly	0
","	0
selective	0
serotonin	1
reuptake	2
inhibitors	2
[	0
SSRIs	1
]	0
)	0
","	0
use	0
and	0
type	0
of	0
mood	0
stabilizers	0
(	0
lithium	1
vs	0
.	0
anticonvulsants	0
)	0
","	0
and	0
temperament	0
of	0
the	0
patient	0
","	0
assessed	0
during	0
a	0
normothymic	0
period	0
using	0
the	0
hyperthymia	0
component	0
of	0
the	0
Semi	0
-	0
structured	0
Affective	0
Temperament	0
Interview	0
.	0
RESULTS	0
:	0
Switches	0
to	0
hypomania	3
or	0
mania	3
occurred	0
in	0
27	0
%	0
of	0
all	0
patients	0
(	0
N	0
=	0
12	0
)	0
(	0
and	0
in	0
24	0
%	0
of	0
the	0
subgroup	0
of	0
patients	0
treated	0
with	0
SSRIs	1
[	0
8	0
/	0
33	0
]	0
)	0
;	0
16	0
%	0
(	0
N	0
=	0
7	0
)	0
experienced	0
manic	3
episodes	0
","	0
and	0
11	0
%	0
(	0
N	0
=	0
5	0
)	0
experienced	0
hypomanic	3
episodes	0
.	0
Sex	0
","	0
age	0
","	0
diagnosis	0
(	0
bipolar	3
I	4
vs	0
.	0
bipolar	3
II	4
)	0
","	0
and	0
additional	0
treatment	0
did	0
not	0
affect	0
the	0
risk	0
of	0
switching	0
.	0
The	0
incidence	0
of	0
mood	0
switches	0
seemed	0
not	0
to	0
differ	0
between	0
patients	0
receiving	0
an	0
anticonvulsant	0
and	0
those	0
receiving	0
no	0
mood	0
stabilizer	0
.	0
In	0
contrast	0
","	0
mood	0
switches	0
were	0
less	0
frequent	0
in	0
patients	0
receiving	0
lithium	1
(	0
15	0
%	0
","	0
4	0
/	0
26	0
)	0
than	0
in	0
patients	0
not	0
treated	0
with	0
lithium	1
(	0
44	0
%	0
","	0
8	0
/	0
18	0
;	0
p	0
=	0
.	0
4	0
)	0
.	0
The	0
number	0
of	0
previous	0
manic	3
episodes	0
did	0
not	0
affect	0
the	0
probability	0
of	0
switching	0
","	0
whereas	0
a	0
high	0
score	0
on	0
the	0
hyperthymia	0
component	0
of	0
the	0
Semistructured	0
Affective	0
Temperament	0
Interview	0
was	0
associated	0
with	0
a	0
greater	0
risk	0
of	0
switching	0
(	0
p	0
=	0
.	0
8	0
)	0
.	0
C0NCLUSI0N	0
:	0
The	0
frequency	0
of	0
mood	0
switching	0
associated	0
with	0
acute	0
antidepressant	1
therapy	0
may	0
be	0
reduced	0
by	0
lithium	1
treatment	0
.	0
Particular	0
attention	0
should	0
be	0
paid	0
to	0
patients	0
with	0
a	0
hyperthymic	0
temperament	0
","	0
who	0
have	0
a	0
greater	0
risk	0
of	0
mood	0
switches	0
.	0
Peritubular	0
capillary	0
basement	0
membrane	0
reduplication	0
in	0
allografts	0
and	0
native	0
kidney	3
disease	4
:	0
a	0
clinicopathologic	0
study	0
of	0
278	0
consecutive	0
renal	0
specimens	0
.	0
BACKGR0UND	0
:	0
An	0
association	0
has	0
been	0
found	0
between	0
transplant	3
glomerulopathy	4
(	0
TG	3
)	0
and	0
reduplication	0
of	0
peritubular	0
capillary	0
basement	0
membranes	0
(	0
PTCR	0
)	0
.	0
Although	0
such	0
an	0
association	0
is	0
of	0
practical	0
and	0
theoretical	0
importance	0
","	0
only	0
one	0
prospective	0
study	0
has	0
tried	0
to	0
confirm	0
it	0
.	0
METH0DS	0
:	0
We	0
examined	0
278	0
consecutive	0
renal	0
specimens	0
(	0
from	0
135	0
transplants	0
and	0
143	0
native	0
kidneys	0
)	0
for	0
ultrastructural	0
evidence	0
of	0
PTCR	0
.	0
In	0
addition	0
to	0
renal	0
allografts	0
with	0
TG	3
","	0
we	0
also	0
examined	0
grafts	0
with	0
acute	0
rejection	0
","	0
recurrent	0
glomerulonephritis	3
","	0
chronic	3
allograft	4
nephropathy	4
and	0
stable	0
grafts	0
(	0
"	0
protocol	0
biopsies	0
"	0
)	0
.	0
Native	0
kidney	0
specimens	0
included	0
a	0
wide	0
range	0
of	0
glomerulopathies	3
as	0
well	0
as	0
cases	0
of	0
thrombotic	3
microangiopathy	4
","	0
malignant	3
hypertension	4
","	0
acute	0
interstitial	3
nephritis	4
","	0
and	0
acute	3
tubular	4
necrosis	4
.	0
RESULTS	0
:	0
We	0
found	0
PTCR	0
in	0
14	0
of	0
15	0
cases	0
of	0
TG	3
","	0
in	0
7	0
transplant	0
biopsy	0
specimens	0
without	0
TG	3
","	0
and	0
in	0
13	0
of	0
143	0
native	0
kidney	0
biopsy	0
specimens	0
.	0
These	0
13	0
included	0
cases	0
of	0
malignant	3
hypertension	4
","	0
thrombotic	3
microangiopathy	4
","	0
lupus	3
nephritis	4
","	0
Henoch	3
-	4
Schonlein	4
nephritis	4
","	0
crescentic	0
glomerulonephritis	3
","	0
and	0
cocaine	1
-	0
related	0
acute	3
renal	4
failure	4
.	0
Mild	0
PTCR	0
in	0
allografts	0
without	0
TG	3
did	0
not	0
predict	0
renal	3
failure	4
or	0
significant	0
proteinuria	3
after	0
follow	0
-	0
up	0
periods	0
of	0
between	0
3	0
months	0
and	0
1	0
year	0
.	0
C0NCLUSI0NS	0
:	0
We	0
conclude	0
that	0
in	0
transplants	0
","	0
there	0
is	0
a	0
strong	0
association	0
between	0
well	0
-	0
developed	0
PTCR	0
and	0
TG	3
","	0
while	0
the	0
significance	0
of	0
mild	0
PTCR	0
and	0
its	0
predictive	0
value	0
in	0
the	0
absence	0
of	0
TG	3
is	0
unclear	0
.	0
PTCR	0
also	0
occurs	0
in	0
certain	0
native	0
kidney	3
diseases	4
","	0
though	0
the	0
association	0
is	0
not	0
as	0
strong	0
as	0
that	0
for	0
TG	3
.	0
We	0
suggest	0
that	0
repeated	0
endothelial	3
injury	4
","	0
including	0
immunologic	3
injury	4
","	0
may	0
be	0
the	0
cause	0
of	0
this	0
lesion	0
both	0
in	0
allografts	0
and	0
native	0
kidneys	0
.	0
Caffeine	1
-	0
induced	0
cardiac	3
arrhythmia	4
:	0
an	0
unrecognised	0
danger	0
of	0
healthfood	0
products	0
.	0
We	0
describe	0
a	0
25	0
-	0
year	0
-	0
old	0
woman	0
with	0
pre	0
-	0
existing	0
mitral	3
valve	4
prolapse	4
who	0
developed	0
intractable	0
ventricular	3
fibrillation	4
after	0
consuming	0
a	0
"	0
natural	0
energy	0
"	0
guarana	0
health	0
drink	0
containing	0
a	0
high	0
concentration	0
of	0
caffeine	1
.	0
This	0
case	0
highlights	0
the	0
need	0
for	0
adequate	0
labelling	0
and	0
regulation	0
of	0
such	0
products	0
.	0
Conformationally	0
restricted	0
analogs	0
of	0
BD1008	1
and	0
an	0
antisense	0
oligodeoxynucleotide	1
targeting	0
sigma1	0
receptors	0
produce	0
anti	0
-	0
cocaine	1
effects	0
in	0
mice	0
.	0
Cocaine	1
'	0
s	0
ability	0
to	0
interact	0
with	0
sigma	0
receptors	0
suggests	0
that	0
these	0
proteins	0
mediate	0
some	0
of	0
its	0
behavioral	0
effects	0
.	0
Therefore	0
","	0
three	0
novel	0
sigma	0
receptor	0
ligands	0
with	0
antagonist	0
activity	0
were	0
evaluated	0
in	0
Swiss	0
Webster	0
mice	0
:	0
BD1018	1
(	0
3S	1
-	2
1	2
-	2
[	2
2	2
-	2
(	2
3	2
","	2
4	2
-	2
dichlorophenyl	2
)	2
ethyl	2
]	2
-	2
1	2
","	2
4	2
-	2
diazabicyclo	2
[	2
4	2
.	2
3	2
.	2
0	2
]	2
nonane	2
)	0
","	0
BD1063	1
(	0
1	1
-	2
[	2
2	2
-	2
(	2
3	2
","	2
4	2
-	2
dichlorophenyl	2
)	2
ethyl	2
]	2
-	2
4	2
-	2
methylpiperazine	2
)	0
","	0
and	0
LR132	1
(	0
1R	0
","	0
2S	0
-	0
(	0
+	0
)	0
-	0
cis	0
-	0
N	0
-	0
[	0
2	0
-	0
(	0
3	0
","	0
4	0
-	0
dichlorophenyl	0
)	0
ethyl	0
]	0
-	0
2	0
-	0
(	0
1	0
-	0
pyrrolidinyl	0
)	0
cyclohexylamine	0
)	0
.	0
Competition	0
binding	0
assays	0
demonstrated	0
that	0
all	0
three	0
compounds	0
have	0
high	0
affinities	0
for	0
sigma1	0
receptors	0
.	0
The	0
three	0
compounds	0
vary	0
in	0
their	0
affinities	0
for	0
sigma2	0
receptors	0
and	0
exhibit	0
negligible	0
affinities	0
for	0
dopamine	1
","	0
opioid	0
","	0
GABA	1
(	0
A	0
)	0
and	0
NMDA	1
receptors	0
.	0
In	0
behavioral	0
studies	0
","	0
pre	0
-	0
treatment	0
of	0
mice	0
with	0
BD1018	1
","	0
BD1063	1
","	0
or	0
LR132	1
significantly	0
attenuated	0
cocaine	1
-	0
induced	0
convulsions	3
and	0
lethality	0
.	0
Moreover	0
","	0
post	0
-	0
treatment	0
with	0
LR132	1
prevented	0
cocaine	1
-	0
induced	0
lethality	0
in	0
a	0
significant	0
proportion	0
of	0
animals	0
.	0
In	0
contrast	0
to	0
the	0
protection	0
provided	0
by	0
the	0
putative	0
antagonists	0
","	0
the	0
well	0
-	0
characterized	0
sigma	0
receptor	0
agonist	0
di	1
-	2
o	2
-	2
tolylguanidine	2
(	0
DTG	1
)	0
and	0
the	0
novel	0
sigma	0
receptor	0
agonist	0
BD1031	1
(	0
3R	1
-	2
1	2
-	2
[	2
2	2
-	2
(	2
3	2
","	2
4	2
-	2
dichlorophenyl	2
)	2
ethyl	2
]	2
-	2
1	2
","	2
4	2
-	2
diazabicyclo	2
[	2
4	2
.	2
3	2
.	2
0	2
]	2
nonane	2
)	0
each	0
worsened	0
the	0
behavioral	0
toxicity	3
of	0
cocaine	1
.	0
At	0
doses	0
where	0
alone	0
","	0
they	0
produced	0
no	0
significant	0
effects	0
on	0
locomotion	0
","	0
BD1018	1
","	0
BD1063	1
and	0
LR132	1
significantly	0
attenuated	0
the	0
locomotor	0
stimulatory	0
effects	0
of	0
cocaine	1
.	0
To	0
further	0
validate	0
the	0
hypothesis	0
that	0
the	0
anti	0
-	0
cocaine	1
effects	0
of	0
the	0
novel	0
ligands	0
involved	0
antagonism	0
of	0
sigma	0
receptors	0
","	0
an	0
antisense	0
oligodeoxynucleotide	1
against	0
sigma1	0
receptors	0
was	0
also	0
shown	0
to	0
significantly	0
attenuate	0
the	0
convulsive	3
and	0
locomotor	0
stimulatory	0
effects	0
of	0
cocaine	1
.	0
Together	0
","	0
the	0
data	0
suggests	0
that	0
functional	0
antagonism	0
of	0
sigma	0
receptors	0
is	0
capable	0
of	0
attenuating	0
a	0
number	0
of	0
cocaine	1
-	0
induced	0
behaviors	0
.	0
Ranitidine	1
-	0
induced	0
acute	0
interstitial	3
nephritis	4
in	0
a	0
cadaveric	0
renal	0
allograft	0
.	0
Ranitidine	1
frequently	0
is	0
used	0
for	0
preventing	0
peptic	0
ulceration	0
after	0
renal	0
transplantation	0
.	0
This	0
drug	0
occasionally	0
has	0
been	0
associated	0
with	0
acute	0
interstitial	3
nephritis	4
in	0
native	0
kidneys	0
.	0
There	0
are	0
no	0
similar	0
reports	0
with	0
renal	0
transplantation	0
.	0
We	0
report	0
a	0
case	0
of	0
ranitidine	1
-	0
induced	0
acute	0
interstitial	3
nephritis	4
in	0
a	0
recipient	0
of	0
a	0
cadaveric	0
renal	0
allograft	0
presenting	0
with	0
acute	0
allograft	0
dysfunction	0
within	0
48	0
hours	0
of	0
exposure	0
to	0
the	0
drug	0
.	0
The	0
biopsy	0
specimen	0
showed	0
pathognomonic	0
features	0
","	0
including	0
eosinophilic	0
infiltration	0
of	0
the	0
interstitial	0
compartment	0
.	0
Allograft	0
function	0
improved	0
rapidly	0
and	0
returned	0
to	0
baseline	0
after	0
stopping	0
the	0
drug	0
.	0
Liver	3
disease	4
caused	0
by	0
propylthiouracil	1
.	0
This	0
report	0
presents	0
the	0
clinical	0
","	0
laboratory	0
","	0
and	0
light	0
and	0
electron	0
microscopic	0
observations	0
on	0
a	0
patient	0
with	0
chronic	3
active	4
(	4
aggressive	4
)	4
hepatitis	4
caused	0
by	0
the	0
administration	0
of	0
propylthiouracil	1
.	0
This	0
is	0
an	0
addition	0
to	0
the	0
list	0
of	0
drugs	0
that	0
must	0
be	0
considered	0
in	0
the	0
evaluation	0
of	0
chronic	0
liver	3
disease	4
.	0
Withdrawal	3
-	4
emergent	4
rabbit	4
syndrome	4
during	0
dose	0
reduction	0
of	0
risperidone	1
.	0
Rabbit	3
syndrome	4
(	0
RS	3
)	0
is	0
a	0
rare	0
extrapyramidal	0
side	0
effect	0
caused	0
by	0
prolonged	0
neuroleptic	0
medication	0
.	0
Here	0
we	0
present	0
a	0
case	0
of	0
withdrawal	3
-	4
emergent	4
RS	4
","	0
which	0
is	0
the	0
first	0
of	0
its	0
kind	0
to	0
be	0
reported	0
.	0
The	0
patient	0
developed	0
RS	3
during	0
dose	0
reduction	0
of	0
risperidone	1
.	0
The	0
symptom	0
was	0
treated	0
successfully	0
with	0
trihexyphenidyl	1
anticholinergic	0
therapy	0
.	0
The	0
underlying	0
mechanism	0
of	0
withdrawal	3
-	4
emergent	4
RS	4
in	0
the	0
present	0
case	0
may	0
have	0
been	0
related	0
to	0
the	0
pharmacological	0
profile	0
of	0
risperidone	1
","	0
a	0
serotonin	1
-	0
dopamine	1
antagonist	0
","	0
suggesting	0
the	0
pathophysiologic	0
influence	0
of	0
the	0
serotonin	1
system	0
in	0
the	0
development	0
of	0
RS	3
.	0
Pharmacokinetic	0
/	0
pharmacodynamic	0
assessment	0
of	0
the	0
effects	0
of	0
E4031	1
","	0
cisapride	1
","	0
terfenadine	1
and	0
terodiline	1
on	0
monophasic	0
action	0
potential	0
duration	0
in	0
dog	0
.	0
1	0
.	0
Torsades	3
de	4
pointes	4
(	0
TDP	3
)	0
is	0
a	0
potentially	0
fatal	0
ventricular	3
tachycardia	4
associated	0
with	0
increases	0
in	0
QT	0
interval	0
and	0
monophasic	0
action	0
potential	0
duration	0
(	0
MAPD	0
)	0
.	0
TDP	3
is	0
a	0
side	0
-	0
effect	0
that	0
has	0
led	0
to	0
withdrawal	0
of	0
several	0
drugs	0
from	0
the	0
market	0
(	0
e	0
.	0
g	0
.	0
terfenadine	1
and	0
terodiline	1
)	0
.	0
2	0
.	0
The	0
potential	0
of	0
compounds	0
to	0
cause	0
TDP	3
was	0
evaluated	0
by	0
monitoring	0
their	0
effects	0
on	0
MAPD	0
in	0
dog	0
.	0
Four	0
compounds	0
known	0
to	0
increase	0
QT	0
interval	0
and	0
cause	0
TDP	3
were	0
investigated	0
:	0
terfenadine	1
","	0
terodiline	1
","	0
cisapride	1
and	0
E4031	1
.	0
0n	0
the	0
basis	0
that	0
only	0
free	0
drug	0
in	0
the	0
systemic	0
circulation	0
will	0
elicit	0
a	0
pharmacological	0
response	0
target	0
","	0
free	0
concentrations	0
in	0
plasma	0
were	0
selected	0
to	0
mimic	0
the	0
free	0
drug	0
exposures	0
in	0
man	0
.	0
Infusion	0
regimens	0
were	0
designed	0
that	0
rapidly	0
achieved	0
and	0
maintained	0
target	0
-	0
free	0
concentrations	0
of	0
these	0
drugs	0
in	0
plasma	0
and	0
data	0
on	0
the	0
relationship	0
between	0
free	0
concentration	0
and	0
changes	0
in	0
MAPD	0
were	0
obtained	0
for	0
these	0
compounds	0
.	0
3	0
.	0
These	0
data	0
indicate	0
that	0
the	0
free	0
ED50	0
in	0
plasma	0
for	0
terfenadine	1
(	0
1	0
.	0
9	0
nM	0
)	0
","	0
terodiline	1
(	0
76	0
nM	0
)	0
","	0
cisapride	1
(	0
11	0
nM	0
)	0
and	0
E4031	1
(	0
1	0
.	0
9	0
nM	0
)	0
closely	0
correlate	0
with	0
the	0
free	0
concentration	0
in	0
man	0
causing	0
QT	0
effects	0
.	0
For	0
compounds	0
that	0
have	0
shown	0
TDP	3
in	0
the	0
clinic	0
(	0
terfenadine	1
","	0
terodiline	1
","	0
cisapride	1
)	0
there	0
is	0
little	0
differentiation	0
between	0
the	0
dog	0
ED50	0
and	0
the	0
efficacious	0
free	0
plasma	0
concentrations	0
in	0
man	0
(	0
<	0
10	0
-	0
fold	0
)	0
reflecting	0
their	0
limited	0
safety	0
margins	0
.	0
These	0
data	0
underline	0
the	0
need	0
to	0
maximize	0
the	0
therapeutic	0
ratio	0
with	0
respect	0
to	0
TDP	3
in	0
potential	0
development	0
candidates	0
and	0
the	0
importance	0
of	0
using	0
free	0
drug	0
concentrations	0
in	0
pharmacokinetic	0
/	0
pharmacodynamic	0
studies	0
.	0
Bladder	0
retention	3
of	4
urine	4
as	0
a	0
result	0
of	0
continuous	0
intravenous	0
infusion	0
of	0
fentanyl	1
:	0
2	0
case	0
reports	0
.	0
Sedation	0
has	0
been	0
commonly	0
used	0
in	0
the	0
neonate	0
to	0
decrease	0
the	0
stress	0
and	0
pain	3
from	0
the	0
noxious	0
stimuli	0
and	0
invasive	0
procedures	0
in	0
the	0
neonatal	0
intensive	0
care	0
unit	0
","	0
as	0
well	0
as	0
to	0
facilitate	0
synchrony	0
between	0
ventilator	0
and	0
spontaneous	0
breaths	0
.	0
Fentanyl	1
","	0
an	0
opioid	0
analgesic	0
","	0
is	0
frequently	0
used	0
in	0
the	0
neonatal	0
intensive	0
care	0
unit	0
setting	0
for	0
these	0
very	0
purposes	0
.	0
Various	0
reported	0
side	0
effects	0
of	0
fentanyl	1
administration	0
include	0
chest	3
wall	4
rigidity	4
","	0
hypotension	3
","	0
respiratory	3
depression	4
","	0
and	0
bradycardia	3
.	0
Here	0
","	0
2	0
cases	0
of	0
urinary	3
bladder	4
retention	4
leading	0
to	0
renal	0
pelvocalyceal	0
dilatation	0
mimicking	0
hydronephrosis	3
as	0
a	0
result	0
of	0
continuous	0
infusion	0
of	0
fentanyl	1
are	0
reported	0
.	0
Fatal	0
myeloencephalopathy	3
due	0
to	0
accidental	0
intrathecal	0
vincristin	1
administration	0
:	0
a	0
report	0
of	0
two	0
cases	0
.	0
We	0
report	0
on	0
two	0
fatal	0
cases	0
of	0
accidental	0
intrathecal	0
vincristine	1
instillation	0
in	0
a	0
5	0
-	0
year	0
old	0
girl	0
with	0
recurrent	0
acute	3
lymphoblastic	4
leucemia	4
and	0
a	0
57	0
-	0
year	0
old	0
man	0
with	0
lymphoblastic	3
lymphoma	4
.	0
The	0
girl	0
died	0
seven	0
days	0
","	0
the	0
man	0
four	0
weeks	0
after	0
intrathecal	0
injection	0
of	0
vincristine	1
.	0
Clinically	0
","	0
the	0
onset	0
was	0
characterized	0
by	0
the	0
signs	0
of	0
opistothonus	3
","	4
sensory	4
and	4
motor	4
dysfunction	4
and	0
ascending	0
paralysis	3
.	0
Histological	0
and	0
immunohistochemical	0
investigations	0
(	0
HE	0
-	0
LFB	0
","	0
CD	0
-	0
68	0
","	0
Neurofilament	0
)	0
revealed	0
degeneration	3
of	4
myelin	4
and	4
axons	4
as	0
well	0
as	0
pseudocystic	3
transformation	4
in	0
areas	0
exposed	0
to	0
vincristine	1
","	0
accompanied	0
by	0
secondary	0
changes	0
with	0
numerous	0
prominent	0
macrophages	0
.	0
The	0
clinical	0
course	0
and	0
histopathological	0
results	0
of	0
the	0
two	0
cases	0
are	0
presented	0
.	0
A	0
review	0
of	0
all	0
reported	0
cases	0
in	0
the	0
literature	0
is	0
given	0
.	0
A	0
better	0
controlled	0
regimen	0
for	0
administering	0
vincristine	1
and	0
intrathecal	0
chemotherapy	0
is	0
recommended	0
.	0
Palpebral	3
twitching	4
in	0
a	0
depressed	3
adolescent	0
on	0
citalopram	1
.	0
Current	0
estimates	0
suggest	0
that	0
between	0
0	0
.	0
4	0
%	0
and	0
8	0
.	0
3	0
%	0
of	0
children	0
and	0
adolescents	0
are	0
affected	0
by	0
major	3
depression	4
.	0
We	0
report	0
a	0
favorable	0
response	0
to	0
treatment	0
with	0
citalopram	1
by	0
a	0
15	0
-	0
year	0
-	0
old	0
boy	0
with	0
major	3
depression	4
who	0
exhibited	0
palpebral	3
twitching	4
during	0
his	0
first	0
2	0
weeks	0
of	0
treatment	0
.	0
This	0
may	0
have	0
been	0
a	0
side	0
effect	0
of	0
citalopram	1
as	0
it	0
remitted	0
with	0
redistribution	0
of	0
doses	0
.	0
The	0
3	0
-	0
week	0
sulphasalazine	1
syndrome	0
strikes	0
again	0
.	0
A	0
34	0
-	0
year	0
-	0
old	0
lady	0
developed	0
a	0
constellation	0
of	0
dermatitis	3
","	0
fever	3
","	0
lymphadenopathy	3
and	0
hepatitis	3
","	0
beginning	0
on	0
the	0
17th	0
day	0
of	0
a	0
course	0
of	0
oral	0
sulphasalazine	1
for	0
sero	0
-	0
negative	0
rheumatoid	3
arthritis	4
.	0
Cervical	0
and	0
inguinal	0
lymph	0
node	0
biopsies	0
showed	0
the	0
features	0
of	0
severe	0
necrotising	0
lymphadenitis	3
","	0
associated	0
with	0
erythrophagocytosis	0
and	0
prominent	0
eosinophilic	0
infiltrates	0
","	0
without	0
viral	0
inclusion	0
bodies	0
","	0
suggestive	0
of	0
an	0
adverse	3
drug	4
reaction	4
.	0
A	0
week	0
later	0
","	0
fulminant	0
drug	3
-	4
induced	4
hepatitis	4
","	0
associated	0
with	0
the	0
presence	0
of	0
anti	0
-	0
nuclear	0
autoantibodies	0
(	0
but	0
not	0
with	0
other	0
markers	0
of	0
autoimmunity	3
)	0
","	0
and	0
accompanied	0
by	0
multi	3
-	4
organ	4
failure	4
and	0
sepsis	3
","	0
supervened	0
.	0
She	0
subsequently	0
died	0
some	0
5	0
weeks	0
after	0
the	0
commencement	0
of	0
her	0
drug	0
therapy	0
.	0
Post	0
-	0
mortem	0
examination	0
showed	0
evidence	0
of	0
massive	3
hepatocellular	4
necrosis	4
","	0
acute	0
hypersensitivity	0
myocarditis	3
","	0
focal	0
acute	0
tubulo	0
-	0
interstitial	0
nephritis	3
and	0
extensive	0
bone	3
marrow	4
necrosis	4
","	0
with	0
no	0
evidence	0
of	0
malignancy	3
.	0
It	0
is	0
thought	0
that	0
the	0
clinico	0
-	0
pathological	0
features	0
and	0
chronology	0
of	0
this	0
case	0
bore	0
the	0
hallmarks	0
of	0
the	0
so	0
-	0
called	0
"	0
3	0
-	0
week	0
sulphasalazine	1
syndrome	0
"	0
","	0
a	0
rare	0
","	0
but	0
often	0
fatal	0
","	0
immunoallergic	0
reaction	0
to	0
sulphasalazine	1
.	0
Intravenous	0
administration	0
of	0
prochlorperazine	1
by	0
15	0
-	0
minute	0
infusion	0
versus	0
2	0
-	0
minute	0
bolus	0
does	0
not	0
affect	0
the	0
incidence	0
of	0
akathisia	3
:	0
a	0
prospective	0
","	0
randomized	0
","	0
controlled	0
trial	0
.	0
STUDY	0
0BJECTIVE	0
:	0
We	0
sought	0
to	0
compare	0
the	0
rate	0
of	0
akathisia	3
after	0
administration	0
of	0
intravenous	0
prochlorperazine	1
as	0
a	0
2	0
-	0
minute	0
bolus	0
or	0
15	0
-	0
minute	0
infusion	0
.	0
METH0DS	0
:	0
We	0
conducted	0
a	0
prospective	0
","	0
randomized	0
","	0
double	0
-	0
blind	0
study	0
in	0
the	0
emergency	0
department	0
of	0
a	0
central	0
-	0
city	0
teaching	0
hospital	0
.	0
Patients	0
aged	0
18	0
years	0
or	0
older	0
treated	0
with	0
prochlorperazine	1
for	0
headache	3
","	0
nausea	3
","	0
or	0
vomiting	3
were	0
eligible	0
for	0
inclusion	0
.	0
Study	0
participants	0
were	0
randomized	0
to	0
receive	0
10	0
mg	0
of	0
prochlorperazine	1
administered	0
intravenously	0
by	0
means	0
of	0
2	0
-	0
minute	0
push	0
(	0
bolus	0
group	0
)	0
or	0
10	0
mg	0
diluted	0
in	0
50	0
mL	0
of	0
normal	0
saline	0
solution	0
administered	0
by	0
means	0
of	0
intravenous	0
infusion	0
during	0
a	0
15	0
-	0
minute	0
period	0
(	0
infusion	0
group	0
)	0
.	0
The	0
main	0
outcome	0
was	0
the	0
number	0
of	0
study	0
participants	0
experiencing	0
akathisia	3
within	0
60	0
minutes	0
of	0
administration	0
.	0
Akathisia	0
was	0
defined	0
as	0
either	0
a	0
spontaneous	0
report	0
of	0
restlessness	0
or	0
agitation	3
or	0
a	0
change	0
of	0
2	0
or	0
more	0
in	0
the	0
patient	0
-	0
reported	0
akathisia	3
rating	0
scale	0
and	0
a	0
change	0
of	0
at	0
least	0
1	0
in	0
the	0
investigator	0
-	0
observed	0
akathisia	3
rating	0
scale	0
.	0
The	0
intensity	0
of	0
headache	3
and	0
nausea	3
was	0
measured	0
with	0
a	0
100	0
-	0
mm	0
visual	0
analog	0
scale	0
.	0
RESULTS	0
:	0
0ne	0
hundred	0
patients	0
were	0
enrolled	0
.	0
0ne	0
study	0
participant	0
was	0
excluded	0
after	0
protocol	0
violation	0
.	0
Seventy	0
-	0
three	0
percent	0
(	0
73	0
/	0
99	0
)	0
of	0
the	0
study	0
participants	0
were	0
treated	0
for	0
headache	3
and	0
70	0
%	0
(	0
70	0
/	0
99	0
)	0
for	0
nausea	3
.	0
In	0
the	0
bolus	0
group	0
","	0
26	0
.	0
0	0
%	0
(	0
13	0
/	0
50	0
)	0
had	0
akathisia	3
compared	0
with	0
32	0
.	0
7	0
%	0
(	0
16	0
/	0
49	0
)	0
in	0
the	0
infusion	0
group	0
(	0
Delta	0
=	0
-	0
6	0
.	0
7	0
%	0
;	0
95	0
%	0
confidence	0
interval	0
[	0
CI	0
]	0
-	0
24	0
.	0
6	0
%	0
to	0
11	0
.	0
2	0
%	0
)	0
.	0
The	0
difference	0
between	0
the	0
bolus	0
and	0
infusion	0
groups	0
in	0
the	0
percentage	0
of	0
participants	0
who	0
saw	0
a	0
50	0
%	0
reduction	0
in	0
their	0
headache	3
intensity	0
within	0
30	0
minutes	0
was	0
11	0
.	0
8	0
%	0
(	0
95	0
%	0
CI	0
-	0
9	0
.	0
6	0
%	0
to	0
33	0
.	0
3	0
%	0
)	0
.	0
The	0
difference	0
in	0
the	0
percentage	0
of	0
patients	0
with	0
a	0
50	0
%	0
reduction	0
in	0
their	0
nausea	3
was	0
12	0
.	0
6	0
%	0
(	0
95	0
%	0
CI	0
-	0
4	0
.	0
6	0
%	0
to	0
29	0
.	0
8	0
%	0
)	0
.	0
C0NCLUSI0N	0
:	0
A	0
50	0
%	0
reduction	0
in	0
the	0
incidence	0
of	0
akathisia	3
when	0
prochlorperazine	1
was	0
administered	0
by	0
means	0
of	0
15	0
-	0
minute	0
intravenous	0
infusion	0
versus	0
a	0
2	0
-	0
minute	0
intravenous	0
push	0
was	0
not	0
detected	0
.	0
The	0
efficacy	0
of	0
prochlorperazine	1
in	0
the	0
treatment	0
of	0
headache	3
and	0
nausea	3
likewise	0
did	0
not	0
appear	0
to	0
be	0
affected	0
by	0
the	0
rate	0
of	0
administration	0
","	0
although	0
no	0
formal	0
statistical	0
comparisons	0
were	0
made	0
.	0
Combined	0
antiretroviral	0
therapy	0
causes	0
cardiomyopathy	3
and	0
elevates	0
plasma	0
lactate	1
in	0
transgenic	0
AIDS	3
mice	0
.	0
Highly	0
active	0
antiretroviral	0
therapy	0
(	0
HAART	0
)	0
is	0
implicated	0
in	0
cardiomyopathy	3
(	0
CM	3
)	0
and	0
in	0
elevated	0
plasma	0
lactate	1
(	0
LA	1
)	0
in	0
AIDS	3
through	0
mechanisms	0
of	0
mitochondrial	3
dysfunction	4
.	0
To	0
determine	0
mitochondrial	0
events	0
from	0
HAART	0
in	0
vivo	0
","	0
8	0
-	0
week	0
-	0
old	0
hemizygous	0
transgenic	0
AIDS	3
mice	0
(	0
NL4	0
-	0
3Delta	0
gag	0
/	0
pol	0
;	0
TG	0
)	0
and	0
wild	0
-	0
type	0
FVB	0
/	0
n	0
littermates	0
were	0
treated	0
with	0
the	0
HAART	0
combination	0
of	0
zidovudine	1
","	0
lamivudine	1
","	0
and	0
indinavir	1
or	0
vehicle	0
control	0
for	0
10	0
days	0
or	0
35	0
days	0
.	0
At	0
termination	0
of	0
the	0
experiments	0
","	0
mice	0
underwent	0
echocardiography	0
","	0
quantitation	0
of	0
abundance	0
of	0
molecular	0
markers	0
of	0
CM	3
(	0
ventricular	0
mRNA	0
encoding	0
atrial	0
natriuretic	0
factor	0
[	0
ANF	0
]	0
and	0
sarcoplasmic	0
calcium	1
ATPase	0
[	0
SERCA2	0
]	0
)	0
","	0
and	0
determination	0
of	0
plasma	0
LA	1
.	0
Myocardial	0
histologic	0
features	0
were	0
analyzed	0
semiquantitatively	0
and	0
results	0
were	0
confirmed	0
by	0
transmission	0
electron	0
microscopy	0
.	0
After	0
35	0
days	0
in	0
the	0
TG	0
+	0
HAART	0
cohort	0
","	0
left	0
ventricular	0
mass	0
increased	0
160	0
%	0
by	0
echocardiography	0
.	0
Molecularly	0
","	0
ANF	0
mRNA	0
increased	0
250	0
%	0
and	0
SERCA2	0
mRNA	0
decreased	0
57	0
%	0
.	0
Biochemically	0
","	0
LA	1
was	0
elevated	0
(	0
8	0
.	0
5	0
+	0
/	0
-	0
2	0
.	0
0	0
mM	0
)	0
.	0
Pathologically	0
","	0
granular	0
cytoplasmic	0
changes	0
were	0
found	0
in	0
cardiac	0
myocytes	0
","	0
indicating	0
enlarged	0
","	0
damaged	0
mitochondria	0
.	0
Findings	0
were	0
confirmed	0
ultrastructurally	0
.	0
No	0
changes	0
were	0
found	0
in	0
other	0
cohorts	0
.	0
After	0
10	0
days	0
","	0
only	0
ANF	0
was	0
elevated	0
","	0
and	0
only	0
in	0
the	0
TG	0
+	0
HAART	0
cohort	0
.	0
Results	0
show	0
that	0
cumulative	0
HAART	0
caused	0
mitochondrial	0
CM	3
with	0
elevated	0
LA	1
in	0
AIDS	3
transgenic	0
mice	0
.	0
A	0
Phase	0
II	0
trial	0
of	0
cisplatin	1
plus	0
WR	1
-	2
2721	2
(	0
amifostine	1
)	0
for	0
metastatic	0
breast	3
carcinoma	4
:	0
an	0
Eastern	0
Cooperative	0
0ncology	0
Group	0
Study	0
(	0
E8188	0
)	0
.	0
BACKGR0UND	0
:	0
Cisplatin	1
has	0
minimal	0
antitumor	0
activity	0
when	0
used	0
as	0
second	0
-	0
or	0
third	0
-	0
line	0
treatment	0
of	0
metastatic	0
breast	3
carcinoma	4
.	0
0lder	0
reports	0
suggest	0
an	0
objective	0
response	0
rate	0
of	0
8	0
%	0
when	0
60	0
-	0
120	0
mg	0
/	0
m2	0
of	0
cisplatin	1
is	0
administered	0
every	0
3	0
-	0
4	0
weeks	0
.	0
Although	0
a	0
dose	0
-	0
response	0
effect	0
has	0
been	0
observed	0
with	0
cisplatin	1
","	0
the	0
dose	0
-	0
limiting	0
toxicities	3
associated	0
with	0
cisplatin	1
(	0
e	0
.	0
g	0
.	0
","	0
nephrotoxicity	3
","	0
ototoxicity	3
","	0
and	0
neurotoxicity	3
)	0
have	0
limited	0
its	0
use	0
as	0
a	0
treatment	0
for	0
breast	3
carcinoma	4
.	0
WR	1
-	2
2721	2
or	0
amifostine	1
initially	0
was	0
developed	0
to	0
protect	0
military	0
personnel	0
in	0
the	0
event	0
of	0
nuclear	0
war	0
.	0
Amifostine	1
subsequently	0
was	0
shown	0
to	0
protect	0
normal	0
tissues	0
from	0
the	0
toxic	0
effects	0
of	0
alkylating	1
agents	2
and	0
cisplatin	1
without	0
decreasing	0
the	0
antitumor	0
effect	0
of	0
the	0
chemotherapy	0
.	0
Early	0
trials	0
of	0
cisplatin	1
and	0
amifostine	1
also	0
suggested	0
that	0
the	0
incidence	0
and	0
severity	0
of	0
cisplatin	1
-	0
induced	0
nephrotoxicity	3
","	0
ototoxicity	3
","	0
and	0
neuropathy	3
were	0
reduced	0
.	0
METH0DS	0
:	0
A	0
Phase	0
II	0
study	0
of	0
the	0
combination	0
of	0
cisplatin	1
plus	0
amifostine	1
was	0
conducted	0
in	0
patients	0
with	0
progressive	0
metastatic	0
breast	3
carcinoma	4
who	0
had	0
received	0
one	0
","	0
but	0
not	0
more	0
than	0
one	0
","	0
chemotherapy	0
regimen	0
for	0
metastatic	0
disease	0
.	0
Patients	0
received	0
amifostine	1
","	0
910	0
mg	0
/	0
m2	0
intravenously	0
over	0
15	0
minutes	0
.	0
After	0
completion	0
of	0
the	0
amifostine	1
infusion	0
","	0
cisplatin	1
120	0
mg	0
/	0
m2	0
was	0
administered	0
over	0
30	0
minutes	0
.	0
Intravenous	0
hydration	0
and	0
mannitol	1
was	0
administered	0
before	0
and	0
after	0
cisplatin	1
.	0
Treatment	0
was	0
administered	0
every	0
3	0
weeks	0
until	0
disease	0
progression	0
.	0
RESULTS	0
:	0
Forty	0
-	0
four	0
patients	0
were	0
enrolled	0
in	0
the	0
study	0
of	0
which	0
7	0
(	0
16	0
%	0
)	0
were	0
ineligible	0
.	0
A	0
median	0
of	0
2	0
cycles	0
of	0
therapy	0
was	0
administered	0
to	0
the	0
37	0
eligible	0
patients	0
.	0
Six	0
partial	0
responses	0
were	0
observed	0
for	0
an	0
overall	0
response	0
rate	0
of	0
16	0
%	0
.	0
Most	0
patients	0
(	0
57	0
%	0
)	0
stopped	0
treatment	0
because	0
of	0
disease	0
progression	0
.	0
Neurologic	3
toxicity	4
was	0
reported	0
in	0
52	0
%	0
of	0
patients	0
.	0
Seven	0
different	0
life	0
-	0
threatening	0
toxicities	3
were	0
observed	0
in	0
patients	0
while	0
receiving	0
treatment	0
.	0
C0NCLUSI0NS	0
:	0
The	0
combination	0
of	0
cisplatin	1
and	0
amifostine	1
in	0
this	0
study	0
resulted	0
in	0
an	0
overall	0
response	0
rate	0
of	0
16	0
%	0
.	0
Neither	0
a	0
tumor	3
-	0
protective	0
effect	0
nor	0
reduced	0
toxicity	3
to	0
normal	0
tissues	0
was	0
observed	0
with	0
the	0
addition	0
of	0
amifostine	1
to	0
cisplatin	1
in	0
this	0
trial	0
.	0
0ral	1
contraceptives	2
and	0
the	0
risk	0
of	0
myocardial	3
infarction	4
.	0
BACKGR0UND	0
:	0
An	0
association	0
between	0
the	0
use	0
of	0
oral	1
contraceptives	2
and	0
the	0
risk	0
of	0
myocardial	3
infarction	4
has	0
been	0
found	0
in	0
some	0
","	0
but	0
not	0
all	0
","	0
studies	0
.	0
We	0
investigated	0
this	0
association	0
","	0
according	0
to	0
the	0
type	0
of	0
progestagen	1
included	0
in	0
third	0
-	0
generation	0
(	0
i	0
.	0
e	0
.	0
","	0
desogestrel	1
or	0
gestodene	1
)	0
and	0
second	0
-	0
generation	0
(	0
i	0
.	0
e	0
.	0
","	0
levonorgestrel	1
)	0
oral	1
contraceptives	2
","	0
the	0
dose	0
of	0
estrogen	1
","	0
and	0
the	0
presence	0
or	0
absence	0
of	0
prothrombotic	0
mutations	0
METH0DS	0
:	0
In	0
a	0
nationwide	0
","	0
population	0
-	0
based	0
","	0
case	0
-	0
control	0
study	0
","	0
we	0
identified	0
and	0
enrolled	0
248	0
women	0
18	0
through	0
49	0
years	0
of	0
age	0
who	0
had	0
had	0
a	0
first	0
myocardial	3
infarction	4
between	0
1990	0
and	0
1995	0
and	0
925	0
control	0
women	0
who	0
had	0
not	0
had	0
a	0
myocardial	3
infarction	4
and	0
who	0
were	0
matched	0
for	0
age	0
","	0
calendar	0
year	0
of	0
the	0
index	0
event	0
","	0
and	0
area	0
of	0
residence	0
.	0
Subjects	0
supplied	0
information	0
on	0
oral	1
-	2
contraceptive	2
use	0
and	0
major	0
cardiovascular	0
risk	0
factors	0
.	0
An	0
analysis	0
for	0
factor	0
V	0
Leiden	0
and	0
the	0
G20210A	0
mutation	0
in	0
the	0
prothrombin	0
gene	0
was	0
conducted	0
in	0
217	0
patients	0
and	0
763	0
controls	0
RESULTS	0
:	0
The	0
odds	0
ratio	0
for	0
myocardial	3
infarction	4
among	0
women	0
who	0
used	0
any	0
type	0
of	0
combined	0
oral	1
contraceptive	2
","	0
as	0
compared	0
with	0
nonusers	0
","	0
was	0
2	0
.	0
0	0
(	0
95	0
percent	0
confidence	0
interval	0
","	0
1	0
.	0
5	0
to	0
2	0
.	0
8	0
)	0
.	0
The	0
adjusted	0
odds	0
ratio	0
was	0
2	0
.	0
5	0
(	0
95	0
percent	0
confidence	0
interval	0
","	0
1	0
.	0
5	0
to	0
4	0
.	0
1	0
)	0
among	0
women	0
who	0
used	0
second	0
-	0
generation	0
oral	1
contraceptives	2
and	0
1	0
.	0
3	0
(	0
95	0
percent	0
confidence	0
interval	0
","	0
0	0
.	0
7	0
to	0
2	0
.	0
5	0
)	0
among	0
those	0
who	0
used	0
third	0
-	0
generation	0
oral	1
contraceptives	2
.	0
Among	0
women	0
who	0
used	0
oral	1
contraceptives	2
","	0
the	0
odds	0
ratio	0
was	0
2	0
.	0
1	0
(	0
95	0
percent	0
confidence	0
interval	0
","	0
1	0
.	0
5	0
to	0
3	0
.	0
0	0
)	0
for	0
those	0
without	0
a	0
prothrombotic	0
mutation	0
and	0
1	0
.	0
9	0
(	0
95	0
percent	0
confidence	0
interval	0
","	0
0	0
.	0
6	0
to	0
5	0
.	0
5	0
)	0
for	0
those	0
with	0
a	0
mutation	0
C0NCLUSI0NS	0
:	0
The	0
risk	0
of	0
myocardial	3
infarction	4
was	0
increased	0
among	0
women	0
who	0
used	0
second	0
-	0
generation	0
oral	1
contraceptives	2
.	0
The	0
results	0
with	0
respect	0
to	0
the	0
use	0
of	0
third	0
-	0
generation	0
oral	1
contraceptives	2
were	0
inconclusive	0
but	0
suggested	0
that	0
the	0
risk	0
was	0
lower	0
than	0
the	0
risk	0
associated	0
with	0
second	0
-	0
generation	0
oral	1
contraceptives	2
.	0
The	0
risk	0
of	0
myocardial	3
infarction	4
was	0
similar	0
among	0
women	0
who	0
used	0
oral	1
contraceptives	2
whether	0
or	0
not	0
they	0
had	0
a	0
prothrombotic	0
mutation	0
.	0
End	3
-	4
stage	4
renal	4
disease	4
(	0
ESRD	3
)	0
after	0
orthotopic	0
liver	0
transplantation	0
(	0
0LTX	0
)	0
using	0
calcineurin	0
-	0
based	0
immunotherapy	0
:	0
risk	0
of	0
development	0
and	0
treatment	0
.	0
BACKGR0UND	0
:	0
The	0
calcineurin	0
inhibitors	0
cyclosporine	1
and	0
tacrolimus	1
are	0
both	0
known	0
to	0
be	0
nephrotoxic	3
.	0
Their	0
use	0
in	0
orthotopic	0
liver	0
transplantation	0
(	0
0LTX	0
)	0
has	0
dramatically	0
improved	0
success	0
rates	0
.	0
Recently	0
","	0
however	0
","	0
we	0
have	0
had	0
an	0
increase	0
of	0
patients	0
who	0
are	0
presenting	0
after	0
0LTX	0
with	0
end	3
-	4
stage	4
renal	4
disease	4
(	0
ESRD	3
)	0
.	0
This	0
retrospective	0
study	0
examines	0
the	0
incidence	0
and	0
treatment	0
of	0
ESRD	3
and	0
chronic	3
renal	4
failure	4
(	0
CRF	3
)	0
in	0
0LTX	0
patients	0
.	0
METH0DS	0
:	0
Patients	0
receiving	0
an	0
0LTX	0
only	0
from	0
June	0
1985	0
through	0
December	0
of	0
1994	0
who	0
survived	0
6	0
months	0
postoperatively	0
were	0
studied	0
(	0
n	0
=	0
834	0
)	0
.	0
0ur	0
prospectively	0
collected	0
database	0
was	0
the	0
source	0
of	0
information	0
.	0
Patients	0
were	0
divided	0
into	0
three	0
groups	0
:	0
Controls	0
","	0
no	0
CRF	3
or	0
ESRD	3
","	0
n	0
=	0
748	0
;	0
CRF	3
","	0
sustained	0
serum	0
creatinine	1
>	0
2	0
.	0
5	0
mg	0
/	0
dl	0
","	0
n	0
=	0
41	0
;	0
and	0
ESRD	3
","	0
n	0
=	0
45	0
.	0
Groups	0
were	0
compared	0
for	0
preoperative	0
laboratory	0
variables	0
","	0
diagnosis	0
","	0
postoperative	0
variables	0
","	0
survival	0
","	0
type	0
of	0
ESRD	3
therapy	0
","	0
and	0
survival	0
from	0
onset	0
of	0
ESRD	3
.	0
RESULTS	0
:	0
At	0
13	0
years	0
after	0
0LTX	0
","	0
the	0
incidence	0
of	0
severe	0
renal	3
dysfunction	4
was	0
18	0
.	0
1	0
%	0
(	0
CRF	3
8	0
.	0
6	0
%	0
and	0
ESRD	3
9	0
.	0
5	0
%	0
)	0
.	0
Compared	0
with	0
control	0
patients	0
","	0
CRF	3
and	0
ESRD	3
patients	0
had	0
higher	0
preoperative	0
serum	0
creatinine	1
levels	0
","	0
a	0
greater	0
percentage	0
of	0
patients	0
with	0
hepatorenal	3
syndrome	4
","	0
higher	0
percentage	0
requirement	0
for	0
dialysis	0
in	0
the	0
first	0
3	0
months	0
postoperatively	0
","	0
and	0
a	0
higher	0
1	0
-	0
year	0
serum	0
creatinine	1
.	0
Multivariate	0
stepwise	0
logistic	0
regression	0
analysis	0
using	0
preoperative	0
and	0
postoperative	0
variables	0
identified	0
that	0
an	0
increase	0
of	0
serum	0
creatinine	1
compared	0
with	0
average	0
at	0
1	0
year	0
","	0
3	0
months	0
","	0
and	0
4	0
weeks	0
postoperatively	0
were	0
independent	0
risk	0
factors	0
for	0
the	0
development	0
of	0
CRF	3
or	0
ESRD	3
with	0
odds	0
ratios	0
of	0
2	0
.	0
6	0
","	0
2	0
.	0
2	0
","	0
and	0
1	0
.	0
6	0
","	0
respectively	0
.	0
0verall	0
survival	0
from	0
the	0
time	0
of	0
0LTX	0
was	0
not	0
significantly	0
different	0
among	0
groups	0
","	0
but	0
by	0
year	0
13	0
","	0
the	0
survival	0
of	0
the	0
patients	0
who	0
had	0
ESRD	3
was	0
only	0
28	0
.	0
2	0
%	0
compared	0
with	0
54	0
.	0
6	0
%	0
in	0
the	0
control	0
group	0
.	0
Patients	0
developing	0
ESRD	3
had	0
a	0
6	0
-	0
year	0
survival	0
after	0
onset	0
of	0
ESRD	3
of	0
27	0
%	0
for	0
the	0
patients	0
receiving	0
hemodialysis	0
versus	0
71	0
.	0
4	0
%	0
for	0
the	0
patients	0
developing	0
ESRD	3
who	0
subsequently	0
received	0
kidney	0
transplants	0
.	0
C0NCLUSI0NS	0
:	0
Patients	0
who	0
are	0
more	0
than	0
10	0
years	0
post	0
-	0
0LTX	0
have	0
CRF	3
and	0
ESRD	3
at	0
a	0
high	0
rate	0
.	0
The	0
development	0
of	0
ESRD	3
decreases	0
survival	0
","	0
particularly	0
in	0
those	0
patients	0
treated	0
with	0
dialysis	0
only	0
.	0
Patients	0
who	0
develop	0
ESRD	3
have	0
a	0
higher	0
preoperative	0
and	0
1	0
-	0
year	0
serum	0
creatinine	1
and	0
are	0
more	0
likely	0
to	0
have	0
hepatorenal	3
syndrome	4
.	0
However	0
","	0
an	0
increase	0
of	0
serum	0
creatinine	1
at	0
various	0
times	0
postoperatively	0
is	0
more	0
predictive	0
of	0
the	0
development	0
of	0
CRF	3
or	0
ESRD	3
.	0
New	0
strategies	0
for	0
long	0
-	0
term	0
immunosuppression	0
may	0
be	0
needed	0
to	0
decrease	0
this	0
complication	0
.	0
Epileptic	3
seizures	4
following	0
cortical	0
application	0
of	0
fibrin	0
sealants	0
containing	0
tranexamic	1
acid	2
in	0
rats	0
.	0
BACKGR0UND	0
:	0
Fibrin	0
sealants	0
(	0
FS	0
)	0
derived	0
from	0
human	0
plasma	0
are	0
frequently	0
used	0
in	0
neurosurgery	0
.	0
In	0
order	0
to	0
increase	0
clot	0
stability	0
","	0
FS	0
typically	0
contain	0
aprotinin	0
","	0
a	0
natural	0
fibrinolysis	0
inhibitor	0
.	0
Recently	0
","	0
synthetic	0
fibrinolysis	0
inhibitors	0
such	0
as	0
tranexamic	1
acid	2
(	0
tAMCA	1
)	0
have	0
been	0
considered	0
as	0
substitutes	0
for	0
aprotinin	0
.	0
However	0
","	0
tAMCA	1
has	0
been	0
shown	0
to	0
cause	0
epileptic	3
seizures	4
.	0
We	0
wanted	0
to	0
study	0
whether	0
tAMCA	1
retains	0
its	0
convulsive	3
action	0
if	0
incorporated	0
into	0
a	0
FS	0
.	0
METH0D	0
:	0
FS	0
containing	0
aprotinin	0
or	0
different	0
concentrations	0
of	0
tAMCA	1
(	0
0	0
.	0
5	0
-	0
47	0
.	0
5	0
mg	0
/	0
ml	0
)	0
were	0
applied	0
to	0
the	0
pial	0
surface	0
of	0
the	0
cortex	0
of	0
anaesthetized	0
rats	0
.	0
The	0
response	0
of	0
the	0
animals	0
was	0
evaluated	0
using	0
electroencephalography	0
and	0
by	0
monitoring	0
the	0
clinical	0
behaviour	0
during	0
and	0
after	0
recovery	0
from	0
anaesthesia	0
.	0
FINDINGS	0
:	0
FS	0
containing	0
tAMCA	1
caused	0
paroxysmal	0
brain	0
activity	0
which	0
was	0
associated	0
with	0
distinct	0
convulsive	3
behaviours	0
.	0
The	0
degree	0
of	0
these	0
seizures	3
increased	0
with	0
increasing	0
concentration	0
of	0
tAMCA	1
.	0
Thus	0
","	0
FS	0
containing	0
47	0
.	0
5	0
mg	0
/	0
ml	0
tAMCA	1
evoked	0
generalized	3
seizures	4
in	0
all	0
tested	0
rats	0
(	0
n	0
=	0
6	0
)	0
while	0
the	0
lowest	0
concentration	0
of	0
tAMCA	1
(	0
0	0
.	0
5	0
mg	0
/	0
ml	0
)	0
only	0
evoked	0
brief	0
episodes	0
of	0
jerk	0
-	0
correlated	0
convulsive	3
potentials	0
in	0
1	0
of	0
6	0
rats	0
.	0
In	0
contrast	0
","	0
FS	0
containing	0
aprotinin	0
did	0
not	0
evoke	0
any	0
paroxysmal	0
activity	0
.	0
INTERPRETATI0N	0
:	0
Tranexamic	1
acid	2
retains	0
its	0
convulsive	3
action	0
within	0
FS	0
.	0
Thus	0
","	0
use	0
of	0
FS	0
containing	0
tAMCA	1
for	0
surgery	0
within	0
or	0
close	0
to	0
the	0
CNS	0
may	0
pose	0
a	0
substantial	0
risk	0
to	0
the	0
patient	0
.	0
Sequential	0
observations	0
of	0
exencephaly	3
and	0
subsequent	0
morphological	0
changes	0
by	0
mouse	0
exo	0
utero	0
development	0
system	0
:	0
analysis	0
of	0
the	0
mechanism	0
of	0
transformation	0
from	0
exencephaly	3
to	0
anencephaly	3
.	0
Anencephaly	3
has	0
been	0
suggested	0
to	0
develop	0
from	0
exencephaly	3
;	0
however	0
","	0
there	0
is	0
little	0
direct	0
experimental	0
evidence	0
to	0
support	0
this	0
","	0
and	0
the	0
mechanism	0
of	0
transformation	0
remains	0
unclear	0
.	0
We	0
examined	0
this	0
theory	0
using	0
the	0
exo	0
utero	0
development	0
system	0
that	0
allows	0
direct	0
and	0
sequential	0
observations	0
of	0
mid	0
-	0
to	0
late	0
-	0
gestation	0
mouse	0
embryos	0
.	0
We	0
observed	0
the	0
exencephaly	3
induced	0
by	0
5	1
-	2
azacytidine	2
at	0
embryonic	0
day	0
13	0
.	0
5	0
(	0
E13	0
.	0
5	0
)	0
","	0
let	0
the	0
embryos	0
develop	0
exo	0
utero	0
until	0
E18	0
.	0
5	0
","	0
and	0
re	0
-	0
observed	0
the	0
same	0
embryos	0
at	0
E18	0
.	0
5	0
.	0
We	0
confirmed	0
several	0
cases	0
of	0
transformation	0
from	0
exencephaly	3
to	0
anencephaly	3
.	0
However	0
","	0
in	0
many	0
cases	0
","	0
the	0
exencephalic	3
brain	0
tissue	0
was	0
preserved	0
with	0
more	0
or	0
less	0
reduction	0
during	0
this	0
period	0
.	0
To	0
analyze	0
the	0
transformation	0
patterns	0
","	0
we	0
classified	0
the	0
exencephaly	3
by	0
size	0
and	0
shape	0
of	0
the	0
exencephalic	3
tissue	0
into	0
several	0
types	0
at	0
E13	0
.	0
5	0
and	0
E18	0
.	0
5	0
.	0
It	0
was	0
found	0
that	0
the	0
transformation	0
of	0
exencephalic	3
tissue	0
was	0
not	0
simply	0
size	0
-	0
dependent	0
","	0
and	0
all	0
cases	0
of	0
anencephaly	3
at	0
E18	0
.	0
5	0
resulted	0
from	0
embryos	0
with	0
a	0
large	0
amount	0
of	0
exencephalic	3
tissue	0
at	0
E13	0
.	0
5	0
.	0
Microscopic	0
observation	0
showed	0
the	0
configuration	0
of	0
exencephaly	3
at	0
E13	0
.	0
5	0
","	0
frequent	0
hemorrhaging	3
and	0
detachment	0
of	0
the	0
neural	0
plate	0
from	0
surface	0
ectoderm	0
in	0
the	0
exencephalic	3
head	0
at	0
E15	0
.	0
5	0
","	0
and	0
multiple	0
modes	0
of	0
reduction	0
in	0
the	0
exencephalic	3
tissue	0
at	0
E18	0
.	0
5	0
.	0
From	0
observations	0
of	0
the	0
vasculature	0
","	0
altered	0
distribution	0
patterns	0
of	0
vessels	0
were	0
identified	0
in	0
the	0
exencephalic	3
head	0
.	0
These	0
findings	0
suggest	0
that	0
overgrowth	0
of	0
the	0
exencephalic	3
neural	0
tissue	0
causes	0
the	0
altered	0
distribution	0
patterns	0
of	0
vessels	0
","	0
subsequent	0
peripheral	0
circulatory	3
failure	4
and	0
/	0
or	0
hemorrhaging	3
in	0
various	0
parts	0
of	0
the	0
exencephalic	3
head	0
","	0
leading	0
to	0
the	0
multiple	0
modes	0
of	0
tissue	0
reduction	0
during	0
transformation	0
from	0
exencephaly	3
to	0
anencephaly	3
.	0
99mTc	1
-	2
glucarate	2
for	0
detection	0
of	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
in	0
rats	0
.	0
Infarct	3
-	0
avid	0
radiopharmaceuticals	0
are	0
necessary	0
for	0
rapid	0
and	0
timely	0
diagnosis	0
of	0
acute	0
myocardial	3
infarction	4
.	0
The	0
animal	0
model	0
used	0
to	0
produce	0
infarction	3
implies	0
artery	0
ligation	0
but	0
chemical	0
induction	0
can	0
be	0
easily	0
obtained	0
with	0
isoproterenol	1
.	0
A	0
new	0
infarct	3
-	0
avid	0
radiopharmaceutical	0
based	0
on	0
glucaric	1
acid	2
was	0
prepared	0
in	0
the	0
hospital	0
radiopharmacy	0
of	0
the	0
INCMNSZ	0
.	0
99mTc	1
-	2
glucarate	2
was	0
easy	0
to	0
prepare	0
","	0
stable	0
for	0
96	0
h	0
and	0
was	0
used	0
to	0
study	0
its	0
biodistribution	0
in	0
rats	0
with	0
isoproterenol	1
-	0
induced	0
acute	0
myocardial	3
infarction	4
.	0
Histological	0
studies	0
demonstrated	0
that	0
the	0
rats	0
developed	0
an	0
infarct	3
18	0
h	0
after	0
isoproterenol	1
administration	0
.	0
The	0
rat	0
biodistribution	0
studies	0
showed	0
a	0
rapid	0
blood	0
clearance	0
via	0
the	0
kidneys	0
.	0
Thirty	0
minutes	0
after	0
99mTc	1
-	2
glucarate	2
administration	0
the	0
standardised	0
heart	0
uptake	0
value	0
S	0
(	0
h	0
)	0
UV	0
was	0
4	0
.	0
7	0
in	0
infarcted	0
rat	0
heart	0
which	0
is	0
six	0
times	0
more	0
than	0
in	0
normal	0
rats	0
.	0
R0Is	0
drawn	0
over	0
the	0
gamma	0
camera	0
images	0
showed	0
a	0
ratio	0
of	0
4	0
.	0
4	0
.	0
The	0
high	0
image	0
quality	0
suggests	0
that	0
high	0
contrast	0
images	0
can	0
be	0
obtained	0
in	0
humans	0
and	0
the	0
96	0
h	0
stability	0
makes	0
it	0
an	0
ideal	0
agent	0
to	0
detect	0
","	0
in	0
patients	0
","	0
early	0
cardiac	3
infarction	4
.	0
Bupropion	1
(	0
Zyban	1
)	0
toxicity	3
.	0
Bupropion	1
is	0
a	0
monocyclic	0
antidepressant	1
structurally	0
related	0
to	0
amphetamine	1
.	0
Zyban	1
","	0
a	0
sustained	0
-	0
release	0
formulation	0
of	0
bupropion	1
hydrochloride	2
","	0
was	0
recently	0
released	0
in	0
Ireland	0
","	0
as	0
a	0
smoking	0
cessation	0
aid	0
.	0
In	0
the	0
initial	0
6	0
months	0
since	0
it	0
'	0
s	0
introduction	0
","	0
12	0
overdose	3
cases	0
have	0
been	0
reported	0
to	0
The	0
National	0
Poisons	0
Information	0
Centre	0
.	0
8	0
patients	0
developed	0
symptoms	0
of	0
toxicity	3
.	0
Common	0
features	0
included	0
tachycardia	3
","	0
drowsiness	0
","	0
hallucinations	3
and	0
convulsions	3
.	0
Two	0
patients	0
developed	0
severe	0
cardiac	3
arrhythmias	4
","	0
including	0
one	0
patient	0
who	0
was	0
resuscitated	0
following	0
a	0
cardiac	3
arrest	4
.	0
All	0
patients	0
recovered	0
without	0
sequelae	0
.	0
We	0
report	0
a	0
case	0
of	0
a	0
31	0
year	0
old	0
female	0
who	0
required	0
admission	0
to	0
the	0
Intensive	0
Care	0
Unit	0
for	0
ventilation	0
and	0
full	0
supportive	0
therapy	0
","	0
following	0
ingestion	0
of	0
13	0
.	0
5g	0
bupropion	1
.	0
Recurrent	0
seizures	3
were	0
treated	0
with	0
diazepam	1
and	0
broad	0
complex	0
tachycardia	3
was	0
successfully	0
treated	0
with	0
adenosine	1
.	0
Zyban	1
caused	0
significant	0
neurological	3
and	4
cardiovascular	4
toxicity	4
in	0
overdose	3
.	0
The	0
potential	0
toxic	0
effects	0
should	0
be	0
considered	0
when	0
prescribing	0
it	0
as	0
a	0
smoking	0
cessation	0
aid	0
.	0
GLEPP1	0
receptor	0
tyrosine	1
phosphatase	0
(	0
Ptpro	0
)	0
in	0
rat	0
PAN	1
nephrosis	3
.	0
A	0
marker	0
of	0
acute	0
podocyte	0
injury	0
.	0
Glomerular	0
epithelial	0
protein	0
1	0
(	0
GLEPP1	0
)	0
is	0
a	0
podocyte	0
receptor	0
membrane	0
protein	0
tyrosine	1
phosphatase	0
located	0
on	0
the	0
apical	0
cell	0
membrane	0
of	0
visceral	0
glomerular	0
epithelial	0
cell	0
and	0
foot	0
processes	0
.	0
This	0
receptor	0
plays	0
a	0
role	0
in	0
regulating	0
the	0
structure	0
and	0
function	0
of	0
podocyte	0
foot	0
process	0
.	0
To	0
better	0
understand	0
the	0
utility	0
of	0
GLEPP1	0
as	0
a	0
marker	0
of	0
glomerular	3
injury	4
","	0
the	0
amount	0
and	0
distribution	0
of	0
GLEPP1	0
protein	0
and	0
mRNA	0
were	0
examined	0
by	0
immunohistochemistry	0
","	0
Western	0
blot	0
and	0
RNase	0
protection	0
assay	0
in	0
a	0
model	0
of	0
podocyte	0
injury	0
in	0
the	0
rat	0
.	0
Puromycin	1
aminonucleoside	2
nephrosis	3
was	0
induced	0
by	0
single	0
intraperitoneal	0
injection	0
of	0
puromycin	1
aminonucleoside	2
(	0
PAN	1
","	0
20	0
mg	0
/	0
100g	0
BW	0
)	0
.	0
Tissues	0
were	0
analyzed	0
at	0
0	0
","	0
5	0
","	0
7	0
","	0
11	0
","	0
21	0
","	0
45	0
","	0
80	0
and	0
126	0
days	0
after	0
PAN	1
injection	0
so	0
as	0
to	0
include	0
both	0
the	0
acute	0
phase	0
of	0
proteinuria	3
associated	0
with	0
foot	0
process	0
effacement	0
(	0
days	0
5	0
-	0
11	0
)	0
and	0
the	0
chronic	0
phase	0
of	0
proteinuria	3
associated	0
with	0
glomerulosclerosis	3
(	0
days	0
45	0
-	0
126	0
)	0
.	0
At	0
day	0
5	0
","	0
GLEPP1	0
protein	0
and	0
mRNA	0
were	0
reduced	0
from	0
the	0
normal	0
range	0
(	0
265	0
.	0
2	0
+	0
/	0
-	0
79	0
.	0
6	0
x	0
10	0
(	0
6	0
)	0
moles	0
/	0
glomerulus	0
and	0
100	0
%	0
)	0
to	0
15	0
%	0
of	0
normal	0
(	0
41	0
.	0
8	0
+	0
/	0
-	0
4	0
.	0
8	0
x	0
10	0
(	0
6	0
)	0
moles	0
/	0
glomerulus	0
","	0
p	0
<	0
0	0
.	0
5	0
)	0
.	0
This	0
occurred	0
in	0
association	0
with	0
an	0
increase	0
in	0
urinary	0
protein	0
content	0
from	0
1	0
.	0
8	0
+	0
/	0
-	0
1	0
to	0
99	0
.	0
0	0
+	0
/	0
-	0
61	0
mg	0
/	0
day	0
(	0
p	0
<	0
0	0
.	0
1	0
)	0
.	0
In	0
contrast	0
","	0
podocalyxin	0
did	0
not	0
change	0
significantly	0
at	0
this	0
time	0
.	0
By	0
day	0
11	0
","	0
GLEPP1	0
protein	0
and	0
mRNA	0
had	0
begun	0
to	0
return	0
towards	0
baseline	0
.	0
By	0
day	0
45	0
-	0
126	0
","	0
at	0
a	0
time	0
when	0
glomerular	0
scarring	0
was	0
present	0
","	0
GLEPP1	0
was	0
absent	0
from	0
glomerulosclerotic	0
areas	0
although	0
the	0
total	0
glomerular	0
content	0
of	0
GLEPP1	0
was	0
not	0
different	0
from	0
normal	0
.	0
We	0
conclude	0
that	0
GLEPP1	0
expression	0
","	0
unlike	0
podocalyxin	0
","	0
reflects	0
podocyte	0
injury	0
induced	0
by	0
PAN	1
.	0
GLEPP1	0
expression	0
may	0
be	0
a	0
useful	0
marker	0
of	0
podocyte	0
injury	0
.	0
Antithymocyte	1
globulin	2
in	0
the	0
treatment	0
of	0
D	1
-	2
penicillamine	2
-	0
induced	0
aplastic	3
anemia	4
.	0
A	0
patient	0
who	0
received	0
antithymocyte	1
globulin	2
therapy	0
for	0
aplastic	3
anemia	4
due	0
to	0
D	1
-	2
penicillamine	2
therapy	0
is	0
described	0
.	0
Bone	0
marrow	0
recovery	0
and	0
peripheral	0
blood	0
recovery	0
were	0
complete	0
1	0
month	0
and	0
3	0
months	0
","	0
respectively	0
","	0
after	0
treatment	0
","	0
and	0
blood	0
transfusion	0
or	0
other	0
therapies	0
were	0
not	0
necessary	0
in	0
a	0
follow	0
-	0
up	0
period	0
of	0
more	0
than	0
2	0
years	0
.	0
Use	0
of	0
antithymocyte	1
globulin	2
may	0
be	0
the	0
optimal	0
treatment	0
of	0
D	1
-	2
penicillamine	2
-	0
induced	0
aplastic	3
anemia	4
.	0
Metamizol	1
potentiates	0
morphine	1
antinociception	0
but	0
not	0
constipation	3
after	0
chronic	0
treatment	0
.	0
This	0
work	0
evaluates	0
the	0
antinociceptive	0
and	0
constipating	3
effects	0
of	0
the	0
combination	0
of	0
3	0
.	0
2	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
morphine	1
with	0
177	0
.	0
8	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
metamizol	1
in	0
acutely	0
and	0
chronically	0
treated	0
(	0
once	0
a	0
day	0
for	0
12	0
days	0
)	0
rats	0
.	0
0n	0
the	0
13th	0
day	0
","	0
antinociceptive	0
effects	0
were	0
assessed	0
using	0
a	0
model	0
of	0
inflammatory	0
nociception	0
","	0
pain	3
-	0
induced	0
functional	0
impairment	0
model	0
","	0
and	0
the	0
charcoal	1
meal	0
test	0
was	0
used	0
to	0
evaluate	0
the	0
intestinal	0
transit	0
.	0
Simultaneous	0
administration	0
of	0
morphine	1
with	0
metamizol	1
resulted	0
in	0
a	0
markedly	0
antinociceptive	0
potentiation	0
and	0
an	0
increasing	0
of	0
the	0
duration	0
of	0
action	0
after	0
a	0
single	0
(	0
298	0
+	0
/	0
-	0
7	0
vs	0
.	0
139	0
+	0
/	0
-	0
36	0
units	0
area	0
(	0
ua	0
)	0
;	0
P	0
<	0
0	0
.	0
1	0
)	0
and	0
repeated	0
administration	0
(	0
280	0
+	0
/	0
-	0
17	0
vs	0
.	0
131	0
+	0
/	0
-	0
22	0
ua	0
;	0
P	0
<	0
0	0
.	0
1	0
)	0
.	0
Antinociceptive	0
effect	0
of	0
morphine	1
was	0
reduced	0
in	0
chronically	0
treated	0
rats	0
(	0
39	0
+	0
/	0
-	0
10	0
vs	0
.	0
18	0
+	0
/	0
-	0
5	0
au	0
)	0
while	0
the	0
combination	0
-	0
induced	0
antinociception	0
was	0
remained	0
similar	0
as	0
an	0
acute	0
treatment	0
(	0
298	0
+	0
/	0
-	0
7	0
vs	0
.	0
280	0
+	0
/	0
-	0
17	0
au	0
)	0
.	0
Acute	0
antinociceptive	0
effects	0
of	0
the	0
combination	0
were	0
partially	0
prevented	0
by	0
3	0
.	0
2	0
mg	0
/	0
kg	0
naloxone	1
s	0
.	0
c	0
.	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
","	0
suggesting	0
the	0
partial	0
involvement	0
of	0
the	0
opioidergic	0
system	0
in	0
the	0
synergism	0
observed	0
.	0
In	0
independent	0
groups	0
","	0
morphine	1
inhibited	0
the	0
intestinal	0
transit	0
in	0
48	0
+	0
/	0
-	0
4	0
%	0
and	0
38	0
+	0
/	0
-	0
4	0
%	0
after	0
acute	0
and	0
chronic	0
treatment	0
","	0
respectively	0
","	0
suggesting	0
that	0
tolerance	0
did	0
not	0
develop	0
to	0
the	0
constipating	3
effects	0
.	0
The	0
combination	0
inhibited	0
intestinal	0
transit	0
similar	0
to	0
that	0
produced	0
by	0
morphine	1
regardless	0
of	0
the	0
time	0
of	0
treatment	0
","	0
suggesting	0
that	0
metamizol	1
did	0
not	0
potentiate	0
morphine	1
-	0
induced	0
constipation	3
.	0
These	0
findings	0
show	0
a	0
significant	0
interaction	0
between	0
morphine	1
and	0
metamizol	1
in	0
chronically	0
treated	0
rats	0
","	0
suggesting	0
that	0
this	0
combination	0
could	0
be	0
useful	0
for	0
the	0
treatment	0
of	0
chronic	3
pain	4
.	0
Ifosfamide	1
encephalopathy	3
presenting	0
with	0
asterixis	3
.	0
CNS	0
toxic	0
effects	0
of	0
the	0
antineoplastic	0
agent	0
ifosfamide	1
(	0
IFX	1
)	0
are	0
frequent	0
and	0
include	0
a	0
variety	0
of	0
neurological	0
symptoms	0
that	0
can	0
limit	0
drug	0
use	0
.	0
We	0
report	0
a	0
case	0
of	0
a	0
51	0
-	0
year	0
-	0
old	0
man	0
who	0
developed	0
severe	0
","	0
disabling	0
negative	0
myoclonus	3
of	0
the	0
upper	0
and	0
lower	0
extremities	0
after	0
the	0
infusion	0
of	0
ifosfamide	1
for	0
plasmacytoma	3
.	0
He	0
was	0
awake	0
","	0
revealed	0
no	0
changes	0
of	0
mental	0
status	0
and	0
at	0
rest	0
there	0
were	0
no	0
further	0
motor	0
symptoms	0
.	0
Cranial	0
magnetic	0
resonance	0
imaging	0
and	0
extensive	0
laboratory	0
studies	0
failed	0
to	0
reveal	0
structural	3
lesions	4
of	4
the	4
brain	4
and	0
metabolic	3
abnormalities	4
.	0
An	0
electroencephalogram	0
showed	0
continuous	0
","	0
generalized	0
irregular	0
slowing	0
with	0
admixed	0
periodic	0
triphasic	0
waves	0
indicating	0
symptomatic	0
encephalopathy	3
.	0
The	0
administration	0
of	0
ifosfamide	1
was	0
discontinued	0
and	0
within	0
12	0
h	0
the	0
asterixis	3
resolved	0
completely	0
.	0
In	0
the	0
patient	0
described	0
","	0
the	0
presence	0
of	0
asterixis	3
during	0
infusion	0
of	0
ifosfamide	1
","	0
normal	0
laboratory	0
findings	0
and	0
imaging	0
studies	0
and	0
the	0
resolution	0
of	0
symptoms	0
following	0
the	0
discontinuation	0
of	0
the	0
drug	0
suggest	0
that	0
negative	0
myoclonus	3
is	0
associated	0
with	0
the	0
use	0
of	0
IFX	1
.	0
Antagonism	0
between	0
interleukin	0
3	0
and	0
erythropoietin	0
in	0
mice	0
with	0
azidothymidine	1
-	0
induced	0
anemia	3
and	0
in	0
bone	0
marrow	0
endothelial	0
cells	0
.	0
Azidothymidine	1
(	0
AZT	1
)	0
-	0
induced	0
anemia	3
in	0
mice	0
can	0
be	0
reversed	0
by	0
the	0
administration	0
of	0
IGF	0
-	0
IL	0
-	0
3	0
(	0
fusion	0
protein	0
of	0
insulin	0
-	0
like	0
growth	0
factor	0
II	0
(	0
IGF	0
II	0
)	0
and	0
interleukin	0
3	0
)	0
.	0
Although	0
interleukin	0
3	0
(	0
IL	0
-	0
3	0
)	0
and	0
erythropoietin	0
(	0
EP0	0
)	0
are	0
known	0
to	0
act	0
synergistically	0
on	0
hematopoietic	0
cell	0
proliferation	0
in	0
vitro	0
","	0
injection	0
of	0
IGF	0
-	0
IL	0
-	0
3	0
and	0
EP0	0
in	0
AZT	1
-	0
treated	0
mice	0
resulted	0
in	0
a	0
reduction	0
of	0
red	0
cells	0
and	0
an	0
increase	0
of	0
plasma	0
EP0	0
levels	0
as	0
compared	0
to	0
animals	0
treated	0
with	0
IGF	0
-	0
IL	0
-	0
3	0
or	0
EP0	0
alone	0
.	0
We	0
tested	0
the	0
hypothesis	0
that	0
the	0
antagonistic	0
effect	0
of	0
IL	0
-	0
3	0
and	0
EP0	0
on	0
erythroid	0
cells	0
may	0
be	0
mediated	0
by	0
endothelial	0
cells	0
.	0
Bovine	0
liver	0
erythroid	0
cells	0
were	0
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human	0
bone	0
marrow	0
endothelial	0
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previously	0
treated	0
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EP0	0
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IGF	0
-	0
IL	0
-	0
3	0
.	0
There	0
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a	0
significant	0
reduction	0
of	0
thymidine	1
incorporation	0
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both	0
erythroid	0
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endothelial	0
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cultures	0
pre	0
-	0
treated	0
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IGF	0
-	0
IL	0
-	0
3	0
and	0
EP0	0
.	0
Endothelial	0
cell	0
culture	0
supernatants	0
separated	0
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ultrafiltration	0
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ultracentrifugation	0
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cells	0
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EP0	0
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IL	0
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significantly	0
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thymidine	1
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cells	0
as	0
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identical	0
fractions	0
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the	0
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acetylcholine	1
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prone	0
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-	0
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mouse	0
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.	0
BACKGR0UND	0
:	0
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-	0
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cholinergic	0
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implicated	0
in	0
epileptogenesis	0
","	0
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","	0
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.	0
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","	0
the	0
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alcohol	1
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genetic	0
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model	0
of	0
ethanol	1
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.	0
METH0DS	0
:	0
Cholinergic	0
convulsant	0
sensitivity	0
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examined	0
in	0
alcohol	1
-	0
na	0
ve	0
Withdrawal	0
Seizure	3
-	0
Prone	0
(	0
WSP	0
)	0
and	0
-	0
Resistant	0
(	0
WSR	0
)	0
mice	0
.	0
Animals	0
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administered	0
nicotine	1
","	0
carbachol	1
","	0
or	0
neostigmine	1
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","	0
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threshold	0
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also	0
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microdialysis	0
to	0
measure	0
basal	0
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potassium	1
-	0
stimulated	0
acetylcholine	1
(	0
ACh	1
)	0
release	0
in	0
the	0
CA1	0
region	0
of	0
the	0
hippocampus	0
.	0
Potassium	1
was	0
applied	0
by	0
reverse	0
dialysis	0
twice	0
","	0
separated	0
by	0
75	0
min	0
.	0
Hippocampal	0
ACh	1
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testing	0
for	0
handling	0
-	0
induced	0
convulsions	3
.	0
RESULTS	0
:	0
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several	0
convulsion	3
endpoints	0
induced	0
by	0
nicotine	1
","	0
carbachol	1
","	0
and	0
neostigmine	1
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significantly	0
greater	0
in	0
WSR	0
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WSP	0
mice	0
.	0
In	0
microdialysis	0
experiments	0
","	0
the	0
lines	0
did	0
not	0
differ	0
in	0
basal	0
release	0
of	0
ACh	1
","	0
and	0
50	0
mM	0
KCl	1
increased	0
ACh	1
output	0
in	0
both	0
lines	0
of	0
mice	0
.	0
However	0
","	0
the	0
increase	0
in	0
release	0
of	0
ACh	1
produced	0
by	0
the	0
first	0
application	0
of	0
KCl	1
was	0
2	0
-	0
fold	0
higher	0
in	0
WSP	0
versus	0
WSR	0
mice	0
.	0
When	0
hippocampal	0
ACh	1
was	0
measured	0
during	0
testing	0
for	0
handling	0
-	0
induced	0
convulsions	3
","	0
extracellular	0
ACh	1
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significantly	0
elevated	0
(	0
192	0
%	0
)	0
in	0
WSP	0
mice	0
","	0
but	0
was	0
nonsignificantly	0
elevated	0
(	0
59	0
%	0
)	0
in	0
WSR	0
mice	0
.	0
C0NCLUSI0NS	0
:	0
These	0
results	0
suggest	0
that	0
differences	0
in	0
cholinergic	0
activity	0
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postsynaptic	0
sensitivity	0
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cholinergic	0
convulsants	3
may	0
be	0
associated	0
with	0
ethanol	1
withdrawal	0
severity	0
and	0
implicate	0
cholinergic	0
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in	0
alcohol	1
withdrawal	0
.	0
Specifically	0
","	0
WSP	0
mice	0
may	0
have	0
lower	0
sensitivity	0
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cholinergic	0
convulsants	3
compared	0
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WSR	0
because	0
of	0
postsynaptic	0
receptor	0
desensitization	0
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on	0
by	0
higher	0
activity	0
of	0
cholinergic	0
neurons	0
.	0
Capsaicin	1
-	0
induced	0
muscle	3
pain	4
alters	0
the	0
excitability	0
of	0
the	0
human	0
jaw	0
-	0
stretch	0
reflex	0
.	0
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pathophysiology	0
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painful	0
temporomandibular	3
disorders	4
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understood	0
","	0
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evidence	0
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muscle	3
pain	4
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afferent	0
fibers	0
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human	0
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length	0
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velocity	0
of	0
the	0
stretch	0
.	0
Capsaicin	1
(	0
10	0
micro	0
g	0
)	0
was	0
injected	0
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the	0
masseter	0
muscle	0
to	0
induce	0
pain	3
in	0
11	0
healthy	0
volunteers	0
.	0
Short	0
-	0
latency	0
reflex	0
responses	0
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masseter	0
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temporalis	0
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a	0
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displacements	0
before	0
","	0
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","	0
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the	0
pain	3
.	0
The	0
normalized	0
reflex	0
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an	0
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velocity	0
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a	0
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","	0
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velocity	0
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reflex	0
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pain	3
","	0
but	0
only	0
at	0
faster	0
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the	0
painful	3
muscle	4
.	0
Increased	0
sensitivity	0
of	0
the	0
fusimotor	0
system	0
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acute	0
muscle	3
pain	4
could	0
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one	0
likely	0
mechanism	0
to	0
explain	0
the	0
findings	0
.	0
Effects	0
of	0
5	0
-	0
HT1B	0
receptor	0
ligands	0
microinjected	0
into	0
the	0
accumbal	0
shell	0
or	0
core	0
on	0
the	0
cocaine	1
-	0
induced	0
locomotor	3
hyperactivity	4
in	0
rats	0
.	0
The	0
present	0
study	0
was	0
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to	0
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5	0
-	0
HT1B	0
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microinjected	0
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the	0
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the	0
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accumbens	0
(	0
the	0
shell	0
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the	0
locomotor	3
hyperactivity	4
induced	0
by	0
cocaine	1
in	0
rats	0
.	0
Male	0
Wistar	0
rats	0
were	0
implanted	0
bilaterally	0
with	0
cannulae	0
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the	0
accumbens	0
shell	0
or	0
core	0
","	0
and	0
then	0
were	0
locally	0
injected	0
with	0
GR	1
55562	2
(	0
an	0
antagonist	0
of	0
5	0
-	0
HT1B	0
receptors	0
)	0
or	0
CP	1
93129	2
(	0
an	0
agonist	0
of	0
5	0
-	0
HT1B	0
receptors	0
)	0
.	0
Given	0
alone	0
to	0
any	0
accumbal	0
subregion	0
","	0
GR	1
55562	2
(	0
0	0
.	0
1	0
-	0
10	0
microg	0
/	0
side	0
)	0
or	0
CP	1
93129	2
(	0
0	0
.	0
1	0
-	0
10	0
microg	0
/	0
side	0
)	0
did	0
not	0
change	0
basal	0
locomotor	0
activity	0
.	0
Systemic	0
cocaine	1
(	0
10	0
mg	0
/	0
kg	0
)	0
significantly	0
increased	0
the	0
locomotor	0
activity	0
of	0
rats	0
.	0
GR	1
55562	2
(	0
0	0
.	0
1	0
-	0
10	0
microg	0
/	0
side	0
)	0
","	0
administered	0
intra	0
-	0
accumbens	0
shell	0
prior	0
to	0
cocaine	1
","	0
dose	0
-	0
dependently	0
attenuated	0
the	0
psychostimulant	0
-	0
induced	0
locomotor	3
hyperactivity	4
.	0
Such	0
attenuation	0
was	0
not	0
found	0
in	0
animals	0
which	0
had	0
been	0
injected	0
with	0
GR	1
55562	2
into	0
the	0
accumbens	0
core	0
.	0
When	0
injected	0
into	0
the	0
accumbens	0
shell	0
(	0
but	0
not	0
the	0
core	0
)	0
before	0
cocaine	1
","	0
CP	1
93129	2
(	0
0	0
.	0
1	0
-	0
10	0
microg	0
/	0
side	0
)	0
enhanced	0
the	0
locomotor	0
response	0
to	0
cocaine	1
;	0
the	0
maximum	0
effect	0
being	0
observed	0
after	0
10	0
microg	0
/	0
side	0
of	0
the	0
agonist	0
.	0
The	0
later	0
enhancement	0
was	0
attenuated	0
after	0
intra	0
-	0
accumbens	0
shell	0
treatment	0
with	0
GR	1
55562	2
(	0
1	0
microg	0
/	0
side	0
)	0
.	0
0ur	0
findings	0
indicate	0
that	0
cocaine	1
induced	0
hyperlocomotion	3
is	0
modified	0
by	0
5	0
-	0
HT1B	0
receptor	0
ligands	0
microinjected	0
into	0
the	0
accumbens	0
shell	0
","	0
but	0
not	0
core	0
","	0
this	0
modification	0
consisting	0
in	0
inhibitory	0
and	0
facilitatory	0
effects	0
of	0
the	0
5	0
-	0
HT1B	0
receptor	0
antagonist	0
(	0
GR	1
55562	2
)	0
and	0
agonist	0
(	0
CP	1
93129	2
)	0
","	0
respectively	0
.	0
In	0
other	0
words	0
","	0
the	0
present	0
results	0
suggest	0
that	0
the	0
accumbal	0
shell	0
5	0
-	0
HT1B	0
receptors	0
play	0
a	0
permissive	0
role	0
in	0
the	0
behavioural	0
response	0
to	0
the	0
psychostimulant	0
.	0
Cocaine	1
related	0
chest	3
pain	4
:	0
are	0
we	0
seeing	0
the	0
tip	0
of	0
an	0
iceberg	0
?	0
The	0
recreational	0
use	0
of	0
cocaine	1
is	0
on	0
the	0
increase	0
.	0
The	0
emergency	0
nurse	0
ought	0
to	0
be	0
familiar	0
with	0
some	0
of	0
the	0
cardiovascular	0
consequences	0
of	0
cocaine	1
use	0
.	0
In	0
particular	0
","	0
the	0
tendency	0
of	0
cocaine	1
to	0
produce	0
chest	3
pain	4
ought	0
to	0
be	0
in	0
the	0
mind	0
of	0
the	0
emergency	0
nurse	0
when	0
faced	0
with	0
a	0
young	0
victim	0
of	0
chest	3
pain	4
who	0
is	0
otherwise	0
at	0
low	0
risk	0
.	0
The	0
mechanism	0
of	0
chest	3
pain	4
related	0
to	0
cocaine	1
use	0
is	0
discussed	0
and	0
treatment	0
dilemmas	0
are	0
discussed	0
.	0
Finally	0
","	0
moral	0
issues	0
relating	0
to	0
the	0
testing	0
of	0
potential	0
cocaine	1
users	0
will	0
be	0
addressed	0
.	0
Crossover	0
comparison	0
of	0
efficacy	0
and	0
preference	0
for	0
rizatriptan	1
10	0
mg	0
versus	0
ergotamine	1
/	0
caffeine	1
in	0
migraine	3
.	0
Rizatriptan	1
is	0
a	0
selective	0
5	1
-	2
HT	2
(	0
1B	0
/	0
1D	0
)	0
receptor	0
agonist	0
with	0
rapid	0
oral	0
absorption	0
and	0
early	0
onset	0
of	0
action	0
in	0
the	0
acute	0
treatment	0
of	0
migraine	3
.	0
This	0
randomized	0
double	0
-	0
blind	0
crossover	0
outpatient	0
study	0
assessed	0
the	0
preference	0
for	0
1	0
rizatriptan	1
10	0
mg	0
tablet	0
to	0
2	0
ergotamine	1
1	0
mg	0
/	0
caffeine	1
100	0
mg	0
tablets	0
in	0
439	0
patients	0
treating	0
a	0
single	0
migraine	3
attack	0
with	0
each	0
therapy	0
.	0
0f	0
patients	0
expressing	0
a	0
preference	0
(	0
89	0
.	0
1	0
%	0
)	0
","	0
more	0
than	0
twice	0
as	0
many	0
preferred	0
rizatriptan	1
to	0
ergotamine	1
/	0
caffeine	1
(	0
69	0
.	0
9	0
vs	0
.	0
30	0
.	0
1	0
%	0
","	0
p	0
<	0
or	0
=	0
0	0
.	0
1	0
)	0
.	0
Faster	0
relief	0
of	0
headache	3
was	0
the	0
most	0
important	0
reason	0
for	0
preference	0
","	0
cited	0
by	0
67	0
.	0
3	0
%	0
of	0
patients	0
preferring	0
rizatriptan	1
and	0
54	0
.	0
2	0
%	0
of	0
patients	0
who	0
preferred	0
ergotamine	1
/	0
caffeine	1
.	0
The	0
co	0
-	0
primary	0
endpoint	0
of	0
being	0
pain	3
free	0
at	0
2	0
h	0
was	0
also	0
in	0
favor	0
of	0
rizatriptan	1
.	0
Forty	0
-	0
nine	0
percent	0
of	0
patients	0
were	0
pain	3
free	0
2	0
h	0
after	0
rizatriptan	1
","	0
compared	0
with	0
24	0
.	0
3	0
%	0
treated	0
with	0
ergotamine	1
/	0
caffeine	1
(	0
p	0
<	0
or	0
=	0
0	0
.	0
1	0
)	0
","	0
rizatriptan	1
being	0
superior	0
within	0
1	0
h	0
of	0
treatment	0
.	0
Headache	3
relief	0
at	0
2	0
h	0
was	0
75	0
.	0
9	0
%	0
for	0
rizatriptan	1
and	0
47	0
.	0
3	0
%	0
for	0
ergotamine	1
/	0
caffeine	1
(	0
p	0
<	0
or	0
=	0
0	0
.	0
1	0
)	0
","	0
with	0
rizatriptan	1
being	0
superior	0
to	0
ergotamine	1
/	0
caffeine	1
within	0
30	0
min	0
of	0
dosing	0
.	0
Almost	0
36	0
%	0
of	0
patients	0
taking	0
rizatriptan	1
were	0
pain	3
free	0
at	0
2	0
h	0
and	0
had	0
no	0
recurrence	0
or	0
need	0
for	0
additional	0
medication	0
within	0
24	0
h	0
","	0
compared	0
to	0
20	0
%	0
of	0
patients	0
on	0
ergotamine	1
/	0
caffeine	1
(	0
p	0
<	0
or	0
=	0
0	0
.	0
1	0
)	0
.	0
Rizatriptan	1
was	0
also	0
superior	0
to	0
ergotamine	1
/	0
caffeine	1
in	0
the	0
proportions	0
of	0
patients	0
with	0
no	0
nausea	3
","	0
vomiting	3
","	0
phonophobia	3
or	0
photophobia	3
and	0
for	0
patients	0
with	0
normal	0
function	0
2	0
h	0
after	0
drug	0
intake	0
(	0
p	0
<	0
or	0
=	0
0	0
.	0
1	0
)	0
.	0
More	0
patients	0
were	0
(	0
completely	0
","	0
very	0
or	0
somewhat	0
)	0
satisfied	0
2	0
h	0
after	0
treatment	0
with	0
rizatriptan	1
(	0
69	0
.	0
8	0
%	0
)	0
than	0
at	0
2	0
h	0
after	0
treatment	0
with	0
ergotamine	1
/	0
caffeine	1
(	0
38	0
.	0
6	0
%	0
","	0
p	0
<	0
or	0
=	0
0	0
.	0
1	0
)	0
.	0
Recurrence	0
rates	0
were	0
31	0
.	0
4	0
%	0
with	0
rizatriptan	1
and	0
15	0
.	0
3	0
%	0
with	0
ergotamine	1
/	0
caffeine	1
.	0
Both	0
active	0
treatments	0
were	0
well	0
tolerated	0
.	0
The	0
most	0
common	0
adverse	0
events	0
(	0
incidence	0
>	0
or	0
=	0
5	0
%	0
in	0
one	0
group	0
)	0
after	0
rizatriptan	1
and	0
ergotamine	1
/	0
caffeine	1
","	0
respectively	0
","	0
were	0
dizziness	3
(	0
6	0
.	0
7	0
and	0
5	0
.	0
3	0
%	0
)	0
","	0
nausea	3
(	0
4	0
.	0
2	0
and	0
8	0
.	0
5	0
%	0
)	0
and	0
somnolence	3
(	0
5	0
.	0
5	0
and	0
2	0
.	0
3	0
%	0
)	0
.	0
Severe	0
ocular	3
and	4
orbital	4
toxicity	4
after	0
intracarotid	0
injection	0
of	0
carboplatin	1
for	0
recurrent	0
glioblastomas	3
.	0
BACKGR0UND	0
:	0
Glioblastoma	3
is	0
a	0
malignant	3
tumor	4
that	0
occurs	0
in	0
the	0
cerebrum	0
during	0
adulthood	0
.	0
With	0
current	0
treatment	0
regimens	0
including	0
combined	0
surgery	0
","	0
radiation	0
and	0
chemotherapy	0
","	0
the	0
average	0
life	0
expectancy	0
of	0
the	0
patients	0
is	0
limited	0
to	0
approximately	0
1	0
year	0
.	0
Therefore	0
","	0
patients	0
with	0
glioblastoma	3
sometimes	0
have	0
intracarotid	0
injection	0
of	0
carcinostatics	0
added	0
to	0
the	0
treatment	0
regimen	0
.	0
Generally	0
","	0
carboplatin	1
is	0
said	0
to	0
have	0
milder	0
side	0
effects	0
than	0
cisplatin	1
","	0
whose	0
ocular	3
and	4
orbital	4
toxicity	4
are	0
well	0
known	0
.	0
However	0
","	0
we	0
experienced	0
a	0
case	0
of	0
severe	0
ocular	3
and	4
orbital	4
toxicity	4
after	0
intracarotid	0
injection	0
of	0
carboplatin	1
","	0
which	0
is	0
infrequently	0
reported	0
.	0
CASE	0
:	0
A	0
58	0
-	0
year	0
-	0
old	0
man	0
received	0
an	0
intracarotid	0
injection	0
of	0
carboplatin	1
for	0
recurrent	0
glioblastomas	3
in	0
his	0
left	0
temporal	0
lobe	0
.	0
He	0
complained	0
of	0
pain	3
and	4
visual	4
disturbance	4
in	4
the	4
ipsilateral	4
eye	4
30	0
h	0
after	0
the	0
injection	0
.	0
Various	0
ocular	0
symptoms	0
and	0
findings	0
caused	0
by	0
carboplatin	1
toxicity	3
were	0
seen	0
.	0
RESULTS	0
:	0
He	0
was	0
treated	0
with	0
intravenous	0
administration	0
of	0
corticosteroids	0
and	0
glycerin	1
for	0
6	0
days	0
after	0
the	0
injection	0
.	0
Although	0
the	0
intraocular	0
pressure	0
elevation	0
caused	0
by	0
secondary	0
acute	0
angle	0
-	0
closure	0
glaucoma	3
decreased	0
and	0
ocular	3
pain	4
diminished	0
","	0
inexorable	0
papilledema	3
and	0
exudative	0
retinal	3
detachment	4
continued	0
for	0
3	0
weeks	0
.	0
Finally	0
","	0
6	0
weeks	0
later	0
","	0
diffuse	0
chorioretinal	3
atrophy	4
with	0
optic	3
atrophy	4
occurred	0
and	0
the	0
vision	0
in	0
his	0
left	0
eye	0
was	0
lost	0
.	0
C0NCLUSI0N	0
:	0
When	0
performing	0
intracarotid	0
injection	0
of	0
carboplatin	1
","	0
we	0
must	0
be	0
aware	0
of	0
its	0
potentially	0
blinding	0
ocular	3
toxicity	4
.	0
It	0
is	0
recommended	0
that	0
further	0
studies	0
and	0
investigations	0
are	0
undertaken	0
in	0
the	0
effort	0
to	0
minimize	0
such	0
severe	0
side	0
effects	0
.	0
Visual	3
hallucinations	4
associated	0
with	0
zonisamide	1
.	0
Zonisamide	1
is	0
a	0
broad	0
-	0
spectrum	0
antiepileptic	0
drug	0
used	0
to	0
treat	0
various	0
types	0
of	0
seizures	3
.	0
Although	0
visual	3
hallucinations	4
have	0
not	0
been	0
reported	0
as	0
an	0
adverse	0
effect	0
of	0
this	0
agent	0
","	0
we	0
describe	0
three	0
patients	0
who	0
experienced	0
complex	0
visual	3
hallucinations	4
and	0
altered	0
mental	0
status	0
after	0
zonisamide	1
treatment	0
was	0
begun	0
or	0
its	0
dosage	0
increased	0
.	0
All	0
three	0
had	0
been	0
diagnosed	0
earlier	0
with	0
epilepsy	3
","	0
and	0
their	0
electroencephalogram	0
(	0
EEG	0
)	0
findings	0
were	0
abnormal	0
.	0
During	0
monitoring	0
","	0
visual	3
hallucinations	4
did	0
not	0
correlate	0
with	0
EEG	0
readings	0
","	0
nor	0
did	0
video	0
recording	0
capture	0
any	0
of	0
the	0
described	0
events	0
.	0
None	0
of	0
the	0
patients	0
had	0
experienced	0
visual	3
hallucinations	4
before	0
this	0
event	0
.	0
The	0
only	0
recent	0
change	0
in	0
their	0
treatment	0
was	0
the	0
introduction	0
or	0
increased	0
dosage	0
of	0
zonisamide	1
.	0
With	0
either	0
discontinuation	0
or	0
decreased	0
dosage	0
of	0
the	0
drug	0
the	0
symptoms	0
disappeared	0
and	0
did	0
not	0
recur	0
.	0
Further	0
observations	0
and	0
reports	0
will	0
help	0
clarify	0
this	0
adverse	0
effect	0
.	0
Until	0
then	0
","	0
clinicians	0
need	0
to	0
be	0
aware	0
of	0
this	0
possible	0
complication	0
associated	0
with	0
zonisamide	1
.	0
Anti	0
-	0
epileptic	3
drugs	0
-	0
induced	0
de	0
novo	0
absence	3
seizures	4
.	0
The	0
authors	0
present	0
three	0
patients	0
with	0
de	0
novo	0
absence	3
epilepsy	4
after	0
administration	0
of	0
carbamazepine	1
and	0
vigabatrin	1
.	0
Despite	0
the	0
underlying	0
diseases	0
","	0
the	0
prognosis	0
for	0
drug	0
-	0
induced	0
de	0
novo	0
absence	3
seizure	4
is	0
good	0
because	0
it	0
subsides	0
rapidly	0
after	0
discontinuing	0
the	0
use	0
of	0
the	0
offending	0
drugs	0
.	0
The	0
gamma	1
-	2
aminobutyric	2
acid	2
-	0
transmitted	0
thalamocortical	0
circuitry	0
accounts	0
for	0
a	0
major	0
part	0
of	0
the	0
underlying	0
neurophysiology	0
of	0
the	0
absence	3
epilepsy	4
.	0
Because	0
drug	0
-	0
induced	0
de	0
novo	0
absence	3
seizure	4
is	0
rare	0
","	0
pro	0
-	0
absence	0
drugs	0
can	0
only	0
be	0
considered	0
a	0
promoting	0
factor	0
.	0
The	0
underlying	0
epileptogenecity	0
of	0
the	0
patients	0
or	0
the	0
synergistic	0
effects	0
of	0
the	0
accompanying	0
drugs	0
is	0
required	0
to	0
trigger	0
the	0
de	0
novo	0
absence	3
seizure	4
.	0
The	0
possibility	0
of	0
drug	0
-	0
induced	0
aggravation	0
should	0
be	0
considered	0
whenever	0
an	0
unexpected	0
increase	0
in	0
seizure	3
frequency	0
and	0
/	0
or	0
new	0
seizure	3
types	0
appear	0
following	0
a	0
change	0
in	0
drug	0
treatment	0
.	0
By	0
understanding	0
the	0
underlying	0
mechanism	0
of	0
absence	3
epilepsy	4
","	0
we	0
can	0
avoid	0
the	0
inappropriate	0
use	0
of	0
anticonvulsants	0
in	0
children	0
with	0
epilepsy	3
and	0
prevent	0
drug	0
-	0
induced	0
absence	3
seizures	4
.	0
Prenatal	0
dexamethasone	1
programs	0
hypertension	3
and	0
renal	3
injury	4
in	0
the	0
rat	0
.	0
Dexamethasone	0
is	0
frequently	0
administered	0
to	0
the	0
developing	0
fetus	0
to	0
accelerate	0
pulmonary	0
development	0
.	0
The	0
purpose	0
of	0
the	0
present	0
study	0
was	0
to	0
determine	0
if	0
prenatal	0
dexamethasone	1
programmed	0
a	0
progressive	0
increase	3
in	4
blood	4
pressure	4
and	0
renal	3
injury	4
in	0
rats	0
.	0
Pregnant	0
rats	0
were	0
given	0
either	0
vehicle	0
or	0
2	0
daily	0
intraperitoneal	0
injections	0
of	0
dexamethasone	1
(	0
0	0
.	0
2	0
mg	0
/	0
kg	0
body	0
weight	0
)	0
on	0
gestational	0
days	0
11	0
and	0
12	0
","	0
13	0
and	0
14	0
","	0
15	0
and	0
16	0
","	0
17	0
and	0
18	0
","	0
or	0
19	0
and	0
20	0
.	0
0ffspring	0
of	0
rats	0
administered	0
dexamethasone	1
on	0
days	0
15	0
and	0
16	0
gestation	0
had	0
a	0
20	0
%	0
reduction	3
in	4
glomerular	4
number	4
compared	0
with	0
control	0
at	0
6	0
to	0
9	0
months	0
of	0
age	0
(	0
22	0
527	0
+	0
/	0
-	0
509	0
versus	0
28	0
50	0
+	0
/	0
-	0
561	0
","	0
P	0
<	0
0	0
.	0
5	0
)	0
","	0
which	0
was	0
comparable	0
to	0
the	0
percent	0
reduction	0
in	0
glomeruli	0
measured	0
at	0
3	0
weeks	0
of	0
age	0
.	0
Six	0
-	0
to	0
9	0
-	0
month	0
old	0
rats	0
receiving	0
prenatal	0
dexamethasone	1
on	0
days	0
17	0
and	0
18	0
of	0
gestation	0
had	0
a	0
17	0
%	0
reduction	0
in	0
glomeruli	0
(	0
23	0
380	0
+	0
/	0
-	0
587	0
)	0
compared	0
with	0
control	0
rats	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
Male	0
rats	0
that	0
received	0
prenatal	0
dexamethasone	1
on	0
days	0
15	0
and	0
16	0
","	0
17	0
and	0
18	0
","	0
and	0
13	0
and	0
14	0
of	0
gestation	0
had	0
elevated	3
blood	4
pressures	4
at	0
6	0
months	0
of	0
age	0
;	0
the	0
latter	0
group	0
did	0
not	0
have	0
a	0
reduction	3
in	4
glomerular	4
number	4
.	0
Adult	0
rats	0
given	0
dexamethasone	1
on	0
days	0
15	0
and	0
16	0
of	0
gestation	0
had	0
more	0
glomeruli	0
with	0
glomerulosclerosis	3
than	0
control	0
rats	0
.	0
This	0
study	0
shows	0
that	0
prenatal	0
dexamethasone	1
in	0
rats	0
results	0
in	0
a	0
reduction	3
in	4
glomerular	4
number	4
","	0
glomerulosclerosis	3
","	0
and	0
hypertension	3
when	0
administered	0
at	0
specific	0
points	0
during	0
gestation	0
.	0
Hypertension	3
was	0
observed	0
in	0
animals	0
that	0
had	0
a	0
reduction	0
in	0
glomeruli	0
as	0
well	0
as	0
in	0
a	0
group	0
that	0
did	0
not	0
have	0
a	0
reduction	3
in	4
glomerular	4
number	4
","	0
suggesting	0
that	0
a	0
reduction	3
in	4
glomerular	4
number	4
is	0
not	0
the	0
sole	0
cause	0
for	0
the	0
development	0
of	0
hypertension	3
.	0
Kidney	0
function	0
and	0
morphology	0
after	0
short	0
-	0
term	0
combination	0
therapy	0
with	0
cyclosporine	1
A	2
","	0
tacrolimus	1
and	0
sirolimus	1
in	0
the	0
rat	0
.	0
BACKGR0UND	0
:	0
Sirolimus	1
(	0
SRL	1
)	0
may	0
supplement	0
calcineurin	0
inhibitors	0
in	0
clinical	0
organ	0
transplantation	0
.	0
These	0
are	0
nephrotoxic	3
","	0
but	0
SRL	1
seems	0
to	0
act	0
differently	0
displaying	0
only	0
minor	0
nephrotoxic	3
effects	0
","	0
although	0
this	0
question	0
is	0
still	0
open	0
.	0
In	0
a	0
number	0
of	0
treatment	0
protocols	0
where	0
SRL	1
was	0
combined	0
with	0
a	0
calcineurin	0
inhibitor	0
indications	0
of	0
a	0
synergistic	0
nephrotoxic	3
effect	0
were	0
described	0
.	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
examine	0
further	0
the	0
renal	0
function	0
","	0
including	0
morphological	0
analysis	0
of	0
the	0
kidneys	0
of	0
male	0
Sprague	0
-	0
Dawley	0
rats	0
treated	0
with	0
either	0
cyclosporine	1
A	2
(	0
CsA	1
)	0
","	0
tacrolimus	1
(	0
FK506	1
)	0
or	0
SRL	1
as	0
monotherapies	0
or	0
in	0
different	0
combinations	0
.	0
METH0DS	0
:	0
For	0
a	0
period	0
of	0
2	0
weeks	0
","	0
CsA	1
15	0
mg	0
/	0
kg	0
/	0
day	0
(	0
given	0
orally	0
)	0
","	0
FK506	1
3	0
.	0
0	0
mg	0
/	0
kg	0
/	0
day	0
(	0
given	0
orally	0
)	0
or	0
SRL	1
0	0
.	0
4	0
mg	0
/	0
kg	0
/	0
day	0
(	0
given	0
intraperitoneally	0
)	0
was	0
administered	0
once	0
a	0
day	0
as	0
these	0
doses	0
have	0
earlier	0
been	0
found	0
to	0
achieve	0
a	0
significant	0
immunosuppressive	0
effect	0
in	0
Sprague	0
-	0
Dawley	0
rats	0
.	0
In	0
the	0
'	0
conscious	0
catheterized	0
rat	0
'	0
model	0
","	0
the	0
glomerular	0
filtration	0
rate	0
(	0
GFR	0
)	0
was	0
measured	0
as	0
the	0
clearance	0
of	0
Cr	0
(	0
EDTA	0
)	0
.	0
The	0
morphological	0
analysis	0
of	0
the	0
kidneys	0
included	0
a	0
semi	0
-	0
quantitative	0
scoring	0
system	0
analysing	0
the	0
degree	0
of	0
striped	0
fibrosis	3
","	0
subcapsular	0
fibrosis	3
and	0
the	0
number	0
of	0
basophilic	0
tubules	0
","	0
plus	0
an	0
additional	0
stereological	0
analysis	0
of	0
the	0
total	0
grade	0
of	0
fibrosis	3
in	0
the	0
cortex	0
stained	0
with	0
Sirius	0
Red	0
.	0
RESULTS	0
:	0
CsA	1
","	0
FK506	1
and	0
SRL	1
all	0
significantly	0
decreased	0
the	0
GFR	0
.	0
A	0
further	0
deterioration	0
was	0
seen	0
when	0
CsA	1
was	0
combined	0
with	0
either	0
FK506	1
or	0
SRL	1
","	0
whereas	0
the	0
GFR	0
remained	0
unchanged	0
in	0
the	0
group	0
treated	0
with	0
FK506	1
plus	0
SRL	1
when	0
compared	0
with	0
treatment	0
with	0
any	0
of	0
the	0
single	0
substances	0
.	0
The	0
morphological	0
changes	0
presented	0
a	0
similar	0
pattern	0
.	0
The	0
semi	0
-	0
quantitative	0
scoring	0
was	0
significantly	0
worst	0
in	0
the	0
group	0
treated	0
with	0
CsA	1
plus	0
SRL	1
(	0
P	0
<	0
0	0
.	0
1	0
compared	0
with	0
controls	0
)	0
and	0
the	0
analysis	0
of	0
the	0
total	0
grade	0
of	0
fibrosis	3
also	0
showed	0
the	0
highest	0
proportion	0
in	0
the	0
same	0
group	0
and	0
was	0
significantly	0
different	0
from	0
controls	0
(	0
P	0
<	0
0	0
.	0
2	0
)	0
.	0
The	0
FK506	1
plus	0
SRL	1
combination	0
showed	0
only	0
a	0
marginally	0
higher	0
degree	0
of	0
fibrosis	3
as	0
compared	0
with	0
controls	0
(	0
P	0
=	0
0	0
.	0
5	0
)	0
.	0
C0NCLUSI0N	0
:	0
This	0
rat	0
study	0
demonstrated	0
a	0
synergistic	0
nephrotoxic	3
effect	0
of	0
CsA	1
plus	0
SRL	1
","	0
whereas	0
FK506	1
plus	0
SRL	1
was	0
better	0
tolerated	0
.	0
Evaluation	0
of	0
cardiac	0
troponin	0
I	0
and	0
T	0
levels	0
as	0
markers	0
of	0
myocardial	3
damage	4
in	0
doxorubicin	1
-	0
induced	0
cardiomyopathy	3
rats	0
","	0
and	0
their	0
relationship	0
with	0
echocardiographic	0
and	0
histological	0
findings	0
.	0
BACKGR0UND	0
:	0
Cardiac	0
troponins	0
I	0
(	0
cTnI	0
)	0
and	0
T	0
(	0
cTnT	0
)	0
have	0
been	0
shown	0
to	0
be	0
highly	0
sensitive	0
and	0
specific	0
markers	0
of	0
myocardial	3
cell	4
injury	4
.	0
We	0
investigated	0
the	0
diagnostic	0
value	0
of	0
cTnI	0
and	0
cTnT	0
for	0
the	0
diagnosis	0
of	0
myocardial	3
damage	4
in	0
a	0
rat	0
model	0
of	0
doxorubicin	1
(	0
D0X	1
)	0
-	0
induced	0
cardiomyopathy	3
","	0
and	0
we	0
examined	0
the	0
relationship	0
between	0
serial	0
cTnI	0
and	0
cTnT	0
with	0
the	0
development	0
of	0
cardiac	3
disorders	4
monitored	0
by	0
echocardiography	0
and	0
histological	0
examinations	0
in	0
this	0
model	0
.	0
METH0DS	0
:	0
Thirty	0
-	0
five	0
Wistar	0
rats	0
were	0
given	0
1	0
.	0
5	0
mg	0
/	0
kg	0
D0X	1
","	0
i	0
.	0
v	0
.	0
","	0
weekly	0
for	0
up	0
to	0
8	0
weeks	0
for	0
a	0
total	0
cumulative	0
dose	0
of	0
12	0
mg	0
/	0
kg	0
BW	0
.	0
Ten	0
rats	0
received	0
saline	0
as	0
a	0
control	0
group	0
.	0
cTnI	0
was	0
measured	0
with	0
Access	0
(	0
R	0
)	0
(	0
ng	0
/	0
ml	0
)	0
and	0
a	0
research	0
immunoassay	0
(	0
pg	0
/	0
ml	0
)	0
","	0
and	0
compared	0
with	0
cTnT	0
","	0
CK	0
-	0
MB	0
mass	0
and	0
CK	0
.	0
By	0
using	0
transthoracic	0
echocardiography	0
","	0
anterior	0
and	0
posterior	0
wall	0
thickness	0
","	0
LV	0
diameters	0
and	0
LV	0
fractional	0
shortening	0
(	0
FS	0
)	0
were	0
measured	0
in	0
all	0
rats	0
before	0
D0X	1
or	0
saline	0
","	0
and	0
at	0
weeks	0
6	0
and	0
9	0
after	0
treatment	0
in	0
all	0
surviving	0
rats	0
.	0
Histology	0
was	0
performed	0
in	0
D0X	1
-	0
rats	0
at	0
6	0
and	0
9	0
weeks	0
after	0
the	0
last	0
D0X	1
dose	0
and	0
in	0
all	0
controls	0
.	0
RESULTS	0
:	0
Eighteen	0
of	0
the	0
D0X	1
rats	0
died	0
prematurely	0
of	0
general	0
toxicity	3
during	0
the	0
9	0
-	0
week	0
period	0
.	0
End	0
-	0
diastolic	0
(	0
ED	0
)	0
and	0
end	0
-	0
systolic	0
(	0
ES	0
)	0
LV	0
diameters	0
/	0
BW	0
significantly	0
increased	0
","	0
whereas	0
LV	0
FS	0
was	0
decreased	0
after	0
9	0
weeks	0
in	0
the	0
D0X	1
group	0
(	0
p	0
<	0
0	0
.	0
1	0
)	0
.	0
These	0
parameters	0
remained	0
unchanged	0
in	0
controls	0
.	0
Histological	0
evaluation	0
of	0
hearts	0
from	0
all	0
rats	0
given	0
D0X	1
revealed	0
significant	0
slight	0
degrees	0
of	0
perivascular	0
and	0
interstitial	0
fibrosis	3
.	0
In	0
7	0
of	0
the	0
18	0
rats	0
","	0
degeneration	0
and	0
myocyte	0
vacuolisation	0
were	0
found	0
.	0
0nly	0
five	0
of	0
the	0
controls	0
exhibited	0
evidence	0
of	0
very	0
slight	0
perivascular	0
fibrosis	3
.	0
A	0
significant	0
rise	0
in	0
cTnT	0
was	0
found	0
in	0
D0X	1
rats	0
after	0
cumulative	0
doses	0
of	0
7	0
.	0
5	0
and	0
12	0
mg	0
/	0
kg	0
in	0
comparison	0
with	0
baseline	0
(	0
p	0
<	0
0	0
.	0
5	0
)	0
.	0
cTnT	0
found	0
in	0
rats	0
after	0
12	0
mg	0
/	0
kg	0
were	0
significantly	0
greater	0
than	0
that	0
found	0
after	0
7	0
.	0
5	0
mg	0
/	0
kg	0
D0X	1
.	0
Maximal	0
cTnI	0
(	0
pg	0
/	0
ml	0
)	0
and	0
cTnT	0
levels	0
were	0
significantly	0
increased	0
in	0
D0X	1
rats	0
compared	0
with	0
controls	0
(	0
p	0
=	0
0	0
.	0
6	0
","	0
0	0
.	0
7	0
)	0
.	0
cTnI	0
(	0
ng	0
/	0
ml	0
)	0
","	0
CK	0
-	0
MB	0
mass	0
and	0
CK	0
remained	0
unchanged	0
in	0
D0X	1
rats	0
compared	0
with	0
controls	0
.	0
All	0
markers	0
remained	0
stable	0
in	0
controls	0
.	0
Analysis	0
of	0
data	0
revealed	0
a	0
significant	0
correlation	0
between	0
maximal	0
cTnT	0
and	0
ED	0
and	0
ES	0
LV	0
diameters	0
/	0
BW	0
(	0
r	0
=	0
0	0
.	0
81	0
and	0
0	0
.	0
65	0
;	0
p	0
<	0
0	0
.	0
1	0
)	0
.	0
A	0
significant	0
relationship	0
was	0
observed	0
between	0
maximal	0
cTnT	0
and	0
the	0
extent	0
of	0
myocardial	0
morphological	0
changes	0
","	0
and	0
between	0
LV	0
diameters	0
/	0
BW	0
and	0
histological	0
findings	0
.	0
C0NCLUSI0NS	0
:	0
Among	0
markers	0
of	0
ischemic	3
injury	4
after	0
D0X	1
in	0
rats	0
","	0
cTnT	0
showed	0
the	0
greatest	0
ability	0
to	0
detect	0
myocardial	3
damage	4
assessed	0
by	0
echocardiographic	0
detection	0
and	0
histological	0
changes	0
.	0
Although	0
there	0
was	0
a	0
discrepancy	0
between	0
the	0
amount	0
of	0
cTnI	0
and	0
cTnT	0
after	0
D0X	1
","	0
probably	0
due	0
to	0
heterogeneity	0
in	0
cross	0
-	0
reactivities	0
of	0
mAbs	0
to	0
various	0
cTnI	0
and	0
cTnT	0
forms	0
","	0
it	0
is	0
likely	0
that	0
cTnT	0
in	0
rats	0
after	0
D0X	1
indicates	0
cell	0
damage	0
determined	0
by	0
the	0
magnitude	0
of	0
injury	0
induced	0
and	0
that	0
cTnT	0
should	0
be	0
a	0
useful	0
marker	0
for	0
the	0
prediction	0
of	0
experimentally	0
induced	0
cardiotoxicity	3
and	0
possibly	0
for	0
cardioprotective	0
experiments	0
.	0
0ctreotide	1
-	0
induced	0
hypoxemia	3
and	0
pulmonary	3
hypertension	4
in	0
premature	0
neonates	0
.	0
The	0
authors	0
report	0
2	0
cases	0
of	0
premature	0
neonates	0
who	0
had	0
enterocutaneous	0
fistula	3
complicating	0
necrotizing	3
enterocolitis	4
.	0
Pulmonary	3
hypertension	4
developed	0
after	0
administration	0
of	0
a	0
somatostatin	0
analogue	0
","	0
octreotide	1
","	0
to	0
enhance	0
resolution	0
of	0
the	0
fistula	3
.	0
The	0
authors	0
discuss	0
the	0
mechanism	0
of	0
the	0
occurrence	0
of	0
this	0
complication	0
and	0
recommend	0
caution	0
of	0
its	0
use	0
in	0
high	0
-	0
risk	0
premature	0
neonates	0
.	0
The	0
risk	0
of	0
venous	3
thromboembolism	4
in	0
women	0
prescribed	0
cyproterone	1
acetate	2
in	0
combination	0
with	0
ethinyl	1
estradiol	2
:	0
a	0
nested	0
cohort	0
analysis	0
and	0
case	0
-	0
control	0
study	0
.	0
BACKGR0UND	0
:	0
Cyproterone	1
acetate	2
combined	0
with	0
ethinyl	1
estradiol	2
(	0
CPA	1
/	0
EE	1
)	0
is	0
licensed	0
in	0
the	0
UK	0
for	0
the	0
treatment	0
of	0
women	0
with	0
acne	3
and	0
hirsutism	3
and	0
is	0
also	0
a	0
treatment	0
option	0
for	0
polycystic	3
ovary	4
syndrome	4
(	0
PC0S	3
)	0
.	0
Previous	0
studies	0
have	0
demonstrated	0
an	0
increased	0
risk	0
of	0
venous	3
thromboembolism	4
(	0
VTE	3
)	0
associated	0
with	0
CPA	1
/	0
EE	1
compared	0
with	0
conventional	0
combined	0
oral	1
contraceptives	2
(	0
C0Cs	0
)	0
.	0
We	0
believe	0
the	0
results	0
of	0
those	0
studies	0
may	0
have	0
been	0
affected	0
by	0
residual	0
confounding	0
.	0
METH0DS	0
:	0
Using	0
the	0
General	0
Practice	0
Research	0
Database	0
we	0
conducted	0
a	0
cohort	0
analysis	0
and	0
case	0
-	0
control	0
study	0
nested	0
within	0
a	0
population	0
of	0
women	0
aged	0
between	0
15	0
and	0
39	0
years	0
with	0
acne	3
","	0
hirsutism	3
or	0
PC0S	3
to	0
estimate	0
the	0
risk	0
of	0
VTE	3
associated	0
with	0
CPA	1
/	0
EE	1
.	0
RESULTS	0
:	0
The	0
age	0
-	0
adjusted	0
incidence	0
rate	0
ratio	0
for	0
CPA	1
/	0
EE	1
versus	0
conventional	0
C0Cs	0
was	0
2	0
.	0
20	0
[	0
95	0
%	0
confidence	0
interval	0
(	0
CI	0
)	0
1	0
.	0
35	0
-	0
3	0
.	0
58	0
]	0
.	0
Using	0
as	0
the	0
reference	0
group	0
women	0
who	0
were	0
not	0
using	0
oral	0
contraception	0
","	0
had	0
no	0
recent	0
pregnancy	0
or	0
menopausal	0
symptoms	0
","	0
the	0
case	0
-	0
control	0
analysis	0
gave	0
an	0
adjusted	0
odds	0
ratio	0
(	0
0R	0
(	0
adj	0
)	0
)	0
of	0
7	0
.	0
44	0
(	0
95	0
%	0
CI	0
3	0
.	0
67	0
-	0
15	0
.	0
8	0
)	0
for	0
CPA	1
/	0
EE	1
use	0
compared	0
with	0
an	0
0R	0
(	0
adj	0
)	0
of	0
2	0
.	0
58	0
(	0
95	0
%	0
CI	0
1	0
.	0
60	0
-	0
4	0
.	0
18	0
)	0
for	0
use	0
of	0
conventional	0
C0Cs	0
.	0
C0NCLUSI0NS	0
:	0
We	0
have	0
demonstrated	0
an	0
increased	0
risk	0
of	0
VTE	3
associated	0
with	0
the	0
use	0
of	0
CPA	1
/	0
EE	1
in	0
women	0
with	0
acne	3
","	0
hirsutism	3
or	0
PC0S	3
although	0
residual	0
confounding	0
by	0
indication	0
cannot	0
be	0
excluded	0
.	0
The	0
effect	0
of	0
treatment	0
with	0
gum	1
Arabic	2
on	0
gentamicin	1
nephrotoxicity	3
in	0
rats	0
:	0
a	0
preliminary	0
study	0
.	0
In	0
the	0
present	0
work	0
we	0
assessed	0
the	0
effect	0
of	0
treatment	0
of	0
rats	0
with	0
gum	1
Arabic	2
on	0
acute	3
renal	4
failure	4
induced	0
by	0
gentamicin	1
(	0
GM	1
)	0
nephrotoxicity	3
.	0
Rats	0
were	0
treated	0
with	0
the	0
vehicle	0
(	0
2	0
mL	0
/	0
kg	0
of	0
distilled	0
water	0
and	0
5	0
%	0
w	0
/	0
v	0
cellulose	0
","	0
10	0
days	0
)	0
","	0
gum	1
Arabic	2
(	0
2	0
mL	0
/	0
kg	0
of	0
a	0
10	0
%	0
w	0
/	0
v	0
aqueous	0
suspension	0
of	0
gum	1
Arabic	2
powder	0
","	0
orally	0
for	0
10	0
days	0
)	0
","	0
or	0
gum	1
Arabic	2
concomitantly	0
with	0
GM	1
(	0
80mg	0
/	0
kg	0
/	0
day	0
intramuscularly	0
","	0
during	0
the	0
last	0
six	0
days	0
of	0
the	0
treatment	0
period	0
)	0
.	0
Nephrotoxicity	3
was	0
assessed	0
by	0
measuring	0
the	0
concentrations	0
of	0
creatinine	1
and	0
urea	1
in	0
the	0
plasma	0
and	0
reduced	0
glutathione	1
(	0
GSH	1
)	0
in	0
the	0
kidney	0
cortex	0
","	0
and	0
by	0
light	0
microscopic	0
examination	0
of	0
kidney	0
sections	0
.	0
The	0
results	0
indicated	0
that	0
concomitant	0
treatment	0
with	0
gum	1
Arabic	2
and	0
GM	1
significantly	0
increased	0
creatinine	1
and	0
urea	1
by	0
about	0
183	0
and	0
239	0
%	0
","	0
respectively	0
(	0
compared	0
to	0
432	0
and	0
346	0
%	0
","	0
respectively	0
","	0
in	0
rats	0
treated	0
with	0
cellulose	0
and	0
GM	1
)	0
","	0
and	0
decreased	0
that	0
of	0
cortical	0
GSH	1
by	0
21	0
%	0
(	0
compared	0
to	0
27	0
%	0
in	0
the	0
cellulose	0
plus	0
GM	1
group	0
)	0
The	0
GM	1
-	0
induced	0
proximal	0
tubular	3
necrosis	4
appeared	0
to	0
be	0
slightly	0
less	0
severe	0
in	0
rats	0
given	0
GM	1
together	0
with	0
gum	1
Arabic	2
than	0
in	0
those	0
given	0
GM	1
and	0
cellulose	0
.	0
It	0
could	0
be	0
inferred	0
that	0
gum	1
Arabic	2
treatment	0
has	0
induced	0
a	0
modest	0
amelioration	0
of	0
some	0
of	0
the	0
histological	0
and	0
biochemical	0
indices	0
of	0
GM	1
nephrotoxicity	3
.	0
Further	0
work	0
is	0
warranted	0
on	0
the	0
effect	0
of	0
the	0
treatments	0
on	0
renal	0
functional	0
aspects	0
in	0
models	0
of	0
chronic	3
renal	4
failure	4
","	0
and	0
on	0
the	0
mechanism	0
(	0
s	0
)	0
involved	0
.	0
Increased	0
frequency	0
of	0
venous	3
thromboembolism	4
with	0
the	0
combination	0
of	0
docetaxel	1
and	0
thalidomide	1
in	0
patients	0
with	0
metastatic	0
androgen	0
-	0
independent	0
prostate	3
cancer	4
.	0
STUDY	0
0BJECTIVE	0
:	0
To	0
evaluate	0
the	0
frequency	0
of	0
venous	3
thromboembolism	4
(	0
VTE	3
)	0
in	0
patients	0
with	0
advanced	0
androgen	0
-	0
independent	0
prostate	3
cancer	4
who	0
were	0
treated	0
with	0
docetaxel	1
alone	0
or	0
in	0
combination	0
with	0
thalidomide	1
.	0
DESIGN	0
:	0
Retrospective	0
analysis	0
of	0
a	0
randomized	0
phase	0
II	0
trial	0
.	0
SETTING	0
:	0
National	0
Institutes	0
of	0
Health	0
clinical	0
research	0
center	0
.	0
PATIENTS	0
:	0
Seventy	0
men	0
","	0
aged	0
50	0
-	0
80	0
years	0
","	0
with	0
advanced	0
androgen	0
-	0
independent	0
prostate	3
cancer	4
.	0
INTERVENTI0N	0
:	0
Each	0
patient	0
received	0
either	0
intravenous	0
docetaxel	1
30	0
mg	0
/	0
m2	0
/	0
week	0
for	0
3	0
consecutive	0
weeks	0
","	0
followed	0
by	0
1	0
week	0
off	0
","	0
or	0
the	0
combination	0
of	0
continuous	0
oral	0
thalidomide	1
200	0
mg	0
every	0
evening	0
plus	0
the	0
same	0
docetaxel	1
regimen	0
.	0
This	0
4	0
-	0
week	0
cycle	0
was	0
repeated	0
until	0
there	0
was	0
evidence	0
of	0
excessive	0
toxicity	3
or	0
disease	0
progression	0
.	0
MEASUREMENTS	0
AND	0
MAIN	0
RESULTS	0
:	0
None	0
of	0
23	0
patients	0
who	0
received	0
docetaxel	1
alone	0
developed	0
VTE	3
","	0
whereas	0
9	0
of	0
47	0
patients	0
(	0
19	0
%	0
)	0
who	0
received	0
docetaxel	1
plus	0
thalidomide	1
developed	0
VTE	3
(	0
p	0
=	0
0	0
.	0
25	0
)	0
.	0
C0NCLUSI0N	0
:	0
The	0
addition	0
of	0
thalidomide	1
to	0
docetaxel	1
in	0
the	0
treatment	0
of	0
prostate	3
cancer	4
significantly	0
increases	0
the	0
frequency	0
of	0
VTE	3
.	0
Clinicians	0
should	0
be	0
aware	0
of	0
this	0
potential	0
complication	0
when	0
adding	0
thalidomide	1
to	0
chemotherapeutic	0
regimens	0
.	0
Ticlopidine	1
-	0
induced	0
cholestatic	3
hepatitis	4
.	0
0BJECTIVE	0
:	0
To	0
report	0
2	0
cases	0
of	0
ticlopidine	1
-	0
induced	0
cholestatic	3
hepatitis	4
","	0
investigate	0
its	0
mechanism	0
","	0
and	0
compare	0
the	0
observed	0
main	0
characteristics	0
with	0
those	0
of	0
the	0
published	0
cases	0
.	0
CASE	0
SUMMARIES	0
:	0
Two	0
patients	0
developed	0
prolonged	0
cholestatic	3
hepatitis	4
after	0
receiving	0
ticlopidine	1
following	0
percutaneous	0
coronary	0
angioplasty	0
","	0
with	0
complete	0
remission	0
during	0
the	0
follow	0
-	0
up	0
period	0
.	0
T	0
-	0
cell	0
stimulation	0
by	0
therapeutic	0
concentration	0
of	0
ticlopidine	1
was	0
demonstrated	0
in	0
vitro	0
in	0
the	0
patients	0
","	0
but	0
not	0
in	0
healthy	0
controls	0
.	0
DISCUSSI0N	0
:	0
Cholestatic	3
hepatitis	4
is	0
a	0
rare	0
complication	0
of	0
the	0
antiplatelet	0
agent	0
ticlopidine	1
;	0
several	0
cases	0
have	0
been	0
reported	0
but	0
few	0
in	0
the	0
English	0
literature	0
.	0
0ur	0
patients	0
developed	0
jaundice	3
following	0
treatment	0
with	0
ticlopidine	1
and	0
showed	0
the	0
clinical	0
and	0
laboratory	0
characteristics	0
of	0
cholestatic	3
hepatitis	4
","	0
which	0
resolved	0
after	0
discontinuation	0
of	0
the	0
drug	0
.	0
Hepatitis	3
may	0
develop	0
weeks	0
after	0
discontinuation	0
of	0
the	0
drug	0
and	0
may	0
run	0
a	0
prolonged	0
course	0
","	0
but	0
complete	0
remission	0
was	0
observed	0
in	0
all	0
reported	0
cases	0
.	0
An	0
objective	0
causality	0
assessment	0
revealed	0
that	0
the	0
adverse	0
drug	0
event	0
was	0
probably	0
related	0
to	0
the	0
use	0
of	0
ticlopidine	1
.	0
The	0
mechanisms	0
of	0
this	0
ticlopidine	1
-	0
induced	0
cholestasis	3
are	0
unclear	0
.	0
Immune	0
mechanisms	0
may	0
be	0
involved	0
in	0
the	0
drug	0
'	0
s	0
hepatotoxicity	3
","	0
as	0
suggested	0
by	0
the	0
T	0
-	0
cell	0
stimulation	0
study	0
reported	0
here	0
.	0
C0NCLUSI0NS	0
:	0
Cholestatic	3
hepatitis	4
is	0
a	0
rare	0
adverse	0
effect	0
of	0
ticlopidine	1
that	0
may	0
be	0
immune	0
mediated	0
.	0
Patients	0
receiving	0
the	0
drug	0
should	0
be	0
monitored	0
with	0
liver	0
function	0
tests	0
along	0
with	0
complete	0
blood	0
cell	0
counts	0
.	0
This	0
complication	0
will	0
be	0
observed	0
even	0
less	0
often	0
in	0
the	0
future	0
as	0
ticlopidine	1
is	0
being	0
replaced	0
by	0
the	0
newer	0
antiplatelet	0
agent	0
clopidogrel	1
.	0
Epithelial	0
sodium	1
channel	0
(	0
ENaC	0
)	0
subunit	0
mRNA	0
and	0
protein	0
expression	0
in	0
rats	0
with	0
puromycin	1
aminonucleoside	2
-	0
induced	0
nephrotic	3
syndrome	4
.	0
In	0
experimental	0
nephrotic	3
syndrome	4
","	0
urinary	0
sodium	1
excretion	0
is	0
decreased	0
during	0
the	0
early	0
phase	0
of	0
the	0
disease	0
.	0
The	0
molecular	0
mechanism	0
(	0
s	0
)	0
leading	0
to	0
salt	0
retention	0
has	0
not	0
been	0
completely	0
elucidated	0
.	0
The	0
rate	0
-	0
limiting	0
constituent	0
of	0
collecting	0
duct	0
sodium	1
transport	0
is	0
the	0
epithelial	0
sodium	1
channel	0
(	0
ENaC	0
)	0
.	0
We	0
examined	0
the	0
abundance	0
of	0
ENaC	0
subunit	0
mRNAs	0
and	0
proteins	0
in	0
puromycin	1
aminonucleoside	2
(	0
PAN	1
)	0
-	0
induced	0
nephrotic	3
syndrome	4
.	0
The	0
time	0
courses	0
of	0
urinary	0
sodium	1
excretion	0
","	0
plasma	0
aldosterone	1
concentration	0
and	0
proteinuria	3
were	0
studied	0
in	0
male	0
Sprague	0
-	0
Dawley	0
rats	0
treated	0
with	0
a	0
single	0
dose	0
of	0
either	0
PAN	1
or	0
vehicle	0
.	0
The	0
relative	0
amounts	0
of	0
alphaENaC	0
","	0
betaENaC	0
and	0
gammaENaC	0
mRNAs	0
were	0
determined	0
in	0
kidneys	0
from	0
these	0
rats	0
by	0
real	0
-	0
time	0
quantitative	0
TaqMan	0
PCR	0
","	0
and	0
the	0
amounts	0
of	0
proteins	0
by	0
Western	0
blot	0
.	0
The	0
kinetics	0
of	0
urinary	0
sodium	1
excretion	0
and	0
the	0
appearance	0
of	0
proteinuria	3
were	0
comparable	0
with	0
those	0
reported	0
previously	0
.	0
Sodium	1
retention	0
occurred	0
on	0
days	0
2	0
","	0
3	0
and	0
6	0
after	0
PAN	1
injection	0
.	0
A	0
significant	0
up	0
-	0
regulation	0
of	0
alphaENaC	0
and	0
betaENaC	0
mRNA	0
abundance	0
on	0
days	0
1	0
and	0
2	0
preceded	0
sodium	1
retention	0
on	0
days	0
2	0
and	0
3	0
.	0
Conversely	0
","	0
down	0
-	0
regulation	0
of	0
alphaENaC	0
","	0
betaENaC	0
and	0
gammaENaC	0
mRNA	0
expression	0
on	0
day	0
3	0
occurred	0
in	0
the	0
presence	0
of	0
high	0
aldosterone	1
concentrations	0
","	0
and	0
was	0
followed	0
by	0
a	0
return	0
of	0
sodium	1
excretion	0
to	0
control	0
values	0
.	0
The	0
amounts	0
of	0
alphaENaC	0
","	0
betaENaC	0
and	0
gammaENaC	0
proteins	0
were	0
not	0
increased	0
during	0
PAN	1
-	0
induced	0
sodium	1
retention	0
.	0
In	0
conclusion	0
","	0
ENaC	0
mRNA	0
expression	0
","	0
especially	0
alphaENaC	0
","	0
is	0
increased	0
in	0
the	0
very	0
early	0
phase	0
of	0
the	0
experimental	0
model	0
of	0
PAN	1
-	0
induced	0
nephrotic	3
syndrome	4
in	0
rats	0
","	0
but	0
appears	0
to	0
escape	0
from	0
the	0
regulation	0
by	0
aldosterone	1
after	0
day	0
3	0
.	0
Sub	0
-	0
chronic	0
low	0
dose	0
gamma	1
-	2
vinyl	2
GABA	2
(	0
vigabatrin	1
)	0
inhibits	0
cocaine	1
-	0
induced	0
increases	0
in	0
nucleus	0
accumbens	0
dopamine	1
.	0
RATI0NALE	0
:	0
gamma	1
-	2
Vinyl	2
GABA	2
(	0
GVG	1
)	0
irreversibly	0
inhibits	0
GABA	1
-	0
transaminase	0
.	0
This	0
non	0
-	0
receptor	0
mediated	0
inhibition	0
requires	0
de	0
novo	0
synthesis	0
for	0
restoration	0
of	0
functional	0
GABA	1
catabolism	0
.	0
0BJECTIVES	0
:	0
Given	0
its	0
preclinical	0
success	0
for	0
treating	0
substance	3
abuse	4
and	0
the	0
increased	0
risk	0
of	0
visual	3
field	4
defects	4
(	0
VFD	3
)	0
associated	0
with	0
cumulative	0
lifetime	0
exposure	0
","	0
we	0
explored	0
the	0
effects	0
of	0
sub	0
-	0
chronic	0
low	0
dose	0
GVG	1
on	0
cocaine	1
-	0
induced	0
increases	0
in	0
nucleus	0
accumbens	0
(	0
NAcc	0
)	0
dopamine	1
(	0
DA	1
)	0
.	0
METH0DS	0
:	0
Using	0
in	0
vivo	0
microdialysis	0
","	0
we	0
compared	0
acute	0
exposure	0
(	0
450	0
mg	0
/	0
kg	0
)	0
to	0
an	0
identical	0
sub	0
-	0
chronic	0
exposure	0
(	0
150	0
mg	0
/	0
kg	0
per	0
day	0
for	0
3	0
days	0
)	0
","	0
followed	0
by	0
1	0
-	0
or	0
3	0
-	0
day	0
washout	0
.	0
Finally	0
","	0
we	0
examined	0
the	0
low	0
dose	0
of	0
150	0
mg	0
/	0
kg	0
(	0
50	0
mg	0
/	0
kg	0
per	0
day	0
)	0
using	0
a	0
similar	0
washout	0
period	0
.	0
RESULTS	0
:	0
Sub	0
-	0
chronic	0
GVG	1
exposure	0
inhibited	0
the	0
effect	0
of	0
cocaine	1
for	0
3	0
days	0
","	0
which	0
exceeded	0
in	0
magnitude	0
and	0
duration	0
the	0
identical	0
acute	0
dose	0
.	0
C0NCLUSI0NS	0
:	0
Sub	0
-	0
chronic	0
low	0
dose	0
GVG	1
potentiates	0
and	0
extends	0
the	0
inhibition	0
of	0
cocaine	1
-	0
induced	0
increases	0
in	0
dopamine	1
","	0
effectively	0
reducing	0
cumulative	0
exposures	0
and	0
the	0
risk	0
for	0
VFDS	0
.	0
MR	0
imaging	0
with	0
quantitative	0
diffusion	0
mapping	0
of	0
tacrolimus	1
-	0
induced	0
neurotoxicity	3
in	0
organ	0
transplant	0
patients	0
.	0
0ur	0
objective	0
was	0
to	0
investigate	0
brain	0
MR	0
imaging	0
findings	0
and	0
the	0
utility	0
of	0
diffusion	0
-	0
weighted	0
(	0
DW	0
)	0
imaging	0
in	0
organ	0
transplant	0
patients	0
who	0
developed	0
neurologic	0
symptoms	0
during	0
tacrolimus	1
therapy	0
.	0
Brain	0
MR	0
studies	0
","	0
including	0
DW	0
imaging	0
","	0
were	0
prospectively	0
performed	0
in	0
14	0
organ	0
transplant	0
patients	0
receiving	0
tacrolimus	1
who	0
developed	0
neurologic	3
complications	4
.	0
In	0
each	0
patient	0
who	0
had	0
abnormalities	0
on	0
the	0
initial	0
MR	0
study	0
","	0
a	0
follow	0
-	0
up	0
MR	0
study	0
was	0
performed	0
1	0
month	0
later	0
.	0
Apparent	0
diffusion	0
coefficient	0
(	0
ADC	0
)	0
values	0
on	0
the	0
initial	0
MR	0
study	0
were	0
correlated	0
with	0
reversibility	0
of	0
the	0
lesions	0
.	0
0f	0
the	0
14	0
patients	0
","	0
5	0
(	0
35	0
.	0
7	0
%	0
)	0
had	0
white	3
matter	4
abnormalities	4
","	0
1	0
(	0
7	0
.	0
1	0
%	0
)	0
had	0
putaminal	3
hemorrhage	4
","	0
and	0
8	0
(	0
57	0
.	0
1	0
%	0
)	0
had	0
normal	0
findings	0
on	0
initial	0
MR	0
images	0
.	0
Among	0
the	0
5	0
patients	0
with	0
white	3
matter	4
abnormalities	4
","	0
4	0
patients	0
(	0
80	0
.	0
0	0
%	0
)	0
showed	0
higher	0
than	0
normal	0
ADC	0
values	0
on	0
initial	0
MR	0
images	0
","	0
and	0
all	0
showed	0
complete	0
resolution	0
on	0
follow	0
-	0
up	0
images	0
.	0
The	0
remaining	0
1	0
patient	0
(	0
20	0
.	0
0	0
%	0
)	0
showed	0
lower	0
than	0
normal	0
ADC	0
value	0
and	0
showed	0
incomplete	0
resolution	0
with	0
cortical	3
laminar	4
necrosis	4
.	0
Diffusion	0
-	0
weighted	0
imaging	0
may	0
be	0
useful	0
in	0
predicting	0
the	0
outcomes	0
of	0
the	0
lesions	0
of	0
tacrolimus	1
-	0
induced	0
neurotoxicity	3
.	0
L	1
-	2
arginine	2
transport	0
in	0
humans	0
with	0
cortisol	1
-	0
induced	0
hypertension	3
.	0
A	0
deficient	0
L	1
-	2
arginine	2
-	0
nitric	1
oxide	2
system	0
is	0
implicated	0
in	0
cortisol	1
-	0
induced	0
hypertension	3
.	0
We	0
investigate	0
whether	0
abnormalities	0
in	0
L	1
-	2
arginine	2
uptake	0
contribute	0
to	0
this	0
deficiency	0
.	0
Eight	0
healthy	0
men	0
were	0
recruited	0
.	0
Hydrocortisone	1
acetate	2
(	0
50	0
mg	0
)	0
was	0
given	0
orally	0
every	0
6	0
hours	0
for	0
24	0
hours	0
after	0
a	0
5	0
-	0
day	0
fixed	0
-	0
salt	0
diet	0
(	0
150	0
mmol	0
/	0
d	0
)	0
.	0
Crossover	0
studies	0
were	0
performed	0
2	0
weeks	0
apart	0
.	0
Thirty	0
milliliters	0
of	0
blood	0
was	0
obtained	0
for	0
isolation	0
of	0
peripheral	0
blood	0
mononuclear	0
cells	0
after	0
each	0
treatment	0
period	0
.	0
L	1
-	2
arginine	2
uptake	0
was	0
assessed	0
in	0
mononuclear	0
cells	0
incubated	0
with	0
L	1
-	2
arginine	2
(	0
1	0
to	0
300	0
micromol	0
/	0
L	0
)	0
","	0
incorporating	0
100	0
nmol	0
/	0
L	0
[	1
3H	2
]	2
-	2
l	2
-	2
arginine	2
for	0
a	0
period	0
of	0
5	0
minutes	0
at	0
37	0
degrees	0
C	0
.	0
Forearm	0
[	1
3H	2
]	2
-	2
L	2
-	2
arginine	2
extraction	0
was	0
calculated	0
after	0
infusion	0
of	0
[	1
3H	2
]	2
-	2
L	2
-	2
arginine	2
into	0
the	0
brachial	0
artery	0
at	0
a	0
rate	0
of	0
100	0
nCi	0
/	0
min	0
for	0
80	0
minutes	0
.	0
Deep	0
forearm	0
venous	0
samples	0
were	0
collected	0
for	0
determination	0
of	0
L	1
-	2
arginine	2
extraction	0
.	0
Plasma	0
cortisol	1
concentrations	0
were	0
significantly	0
raised	0
during	0
the	0
active	0
phase	0
(	0
323	0
+	0
/	0
-	0
43	0
to	0
1082	0
+	0
/	0
-	0
245	0
mmol	0
/	0
L	0
","	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
Systolic	0
blood	0
pressure	0
was	0
elevated	0
by	0
an	0
average	0
of	0
7	0
mm	0
Hg	0
.	0
Neither	0
L	1
-	2
arginine	2
transport	0
into	0
mononuclear	0
cells	0
(	0
placebo	0
vs	0
active	0
","	0
26	0
.	0
3	0
+	0
/	0
-	0
3	0
.	0
6	0
vs	0
29	0
.	0
0	0
+	0
/	0
-	0
2	0
.	0
1	0
pmol	0
/	0
10	0
0	0
cells	0
per	0
5	0
minutes	0
","	0
respectively	0
","	0
at	0
an	0
l	1
-	2
arginine	2
concentration	0
of	0
300	0
micromol	0
/	0
L	0
)	0
nor	0
L	1
-	2
arginine	2
extraction	0
in	0
the	0
forearm	0
(	0
at	0
80	0
minutes	0
","	0
placebo	0
vs	0
active	0
","	0
1	0
868	0
904	0
+	0
/	0
-	0
434	0
962	0
vs	0
2	0
13	0
910	0
+	0
/	0
-	0
770	0
619	0
disintegrations	0
per	0
minute	0
)	0
was	0
affected	0
by	0
cortisol	1
treatment	0
;	0
ie	0
","	0
that	0
L	1
-	2
arginine	2
uptake	0
is	0
not	0
affected	0
by	0
short	0
-	0
term	0
cortisol	1
treatment	0
.	0
We	0
conclude	0
that	0
cortisol	1
-	0
induced	0
increases	3
in	4
blood	4
pressure	4
are	0
not	0
associated	0
with	0
abnormalities	0
in	0
the	0
l	1
-	2
arginine	2
transport	0
system	0
.	0
Amount	0
of	0
bleeding	3
and	0
hematoma	3
size	0
in	0
the	0
collagenase	0
-	0
induced	0
intracerebral	3
hemorrhage	4
rat	0
model	0
.	0
The	0
aggravated	0
risk	0
on	0
intracerebral	3
hemorrhage	4
(	0
ICH	3
)	0
with	0
drugs	0
used	0
for	0
stroke	3
patients	0
should	0
be	0
estimated	0
carefully	0
.	0
We	0
therefore	0
established	0
sensitive	0
quantification	0
methods	0
and	0
provided	0
a	0
rat	0
ICH	3
model	0
for	0
detection	0
of	0
ICH	3
deterioration	0
.	0
In	0
ICH	3
intrastriatally	0
induced	0
by	0
0	0
.	0
14	0
-	0
unit	0
","	0
0	0
.	0
70	0
-	0
unit	0
","	0
and	0
0	0
.	0
350	0
-	0
unit	0
collagenase	0
","	0
the	0
amount	0
of	0
bleeding	3
was	0
measured	0
using	0
a	0
hemoglobin	0
assay	0
developed	0
in	0
the	0
present	0
study	0
and	0
was	0
compared	0
with	0
the	0
morphologically	0
determined	0
hematoma	3
volume	0
.	0
The	0
blood	0
amounts	0
and	0
hematoma	3
volumes	0
were	0
significantly	0
correlated	0
","	0
and	0
the	0
hematoma	3
induced	0
by	0
0	0
.	0
14	0
-	0
unit	0
collagenase	0
was	0
adequate	0
to	0
detect	0
ICH	3
deterioration	0
.	0
In	0
ICH	3
induction	0
using	0
0	0
.	0
14	0
-	0
unit	0
collagenase	0
","	0
heparin	1
enhanced	0
the	0
hematoma	3
volume	0
3	0
.	0
4	0
-	0
fold	0
over	0
that	0
seen	0
in	0
control	0
ICH	3
animals	0
and	0
the	0
bleeding	3
7	0
.	0
6	0
-	0
fold	0
.	0
Data	0
suggest	0
that	0
this	0
sensitive	0
hemoglobin	0
assay	0
is	0
useful	0
for	0
ICH	3
detection	0
","	0
and	0
that	0
a	0
model	0
with	0
a	0
small	0
ICH	3
induced	0
with	0
a	0
low	0
-	0
dose	0
collagenase	0
should	0
be	0
used	0
for	0
evaluation	0
of	0
drugs	0
that	0
may	0
affect	0
ICH	3
.	0
Estradiol	1
reduces	0
seizure	3
-	0
induced	0
hippocampal	3
injury	4
in	0
ovariectomized	0
female	0
but	0
not	0
in	0
male	0
rats	0
.	0
Estrogens	0
protect	0
ovariectomized	0
rats	0
from	0
hippocampal	3
injury	4
induced	0
by	0
kainic	1
acid	2
-	0
induced	0
status	3
epilepticus	4
(	0
SE	3
)	0
.	0
We	0
compared	0
the	0
effects	0
of	0
17beta	1
-	2
estradiol	2
in	0
adult	0
male	0
and	0
ovariectomized	0
female	0
rats	0
subjected	0
to	0
lithium	1
-	0
pilocarpine	1
-	0
induced	0
SE	3
.	0
Rats	0
received	0
subcutaneous	0
injections	0
of	0
17beta	1
-	2
estradiol	2
(	0
2	0
microg	0
/	0
rat	0
)	0
or	0
oil	0
once	0
daily	0
for	0
four	0
consecutive	0
days	0
.	0
SE	3
was	0
induced	0
20	0
h	0
following	0
the	0
second	0
injection	0
and	0
terminated	0
3	0
h	0
later	0
.	0
The	0
extent	0
of	0
silver	1
-	0
stained	0
CA3	0
and	0
CA1	0
hippocampal	0
neurons	0
was	0
evaluated	0
2	0
days	0
after	0
SE	3
.	0
17beta	1
-	2
Estradiol	2
did	0
not	0
alter	0
the	0
onset	0
of	0
first	0
clonus	0
in	0
ovariectomized	0
rats	0
but	0
accelerated	0
it	0
in	0
males	0
.	0
17beta	1
-	2
Estradiol	2
reduced	0
the	0
argyrophilic	0
neurons	0
in	0
the	0
CA1	0
and	0
CA3	0
-	0
C	0
sectors	0
of	0
ovariectomized	0
rats	0
.	0
In	0
males	0
","	0
estradiol	1
increased	0
the	0
total	0
damage	0
score	0
.	0
These	0
findings	0
suggest	0
that	0
the	0
effects	0
of	0
estradiol	1
on	0
seizure	3
threshold	0
and	0
damage	0
may	0
be	0
altered	0
by	0
sex	0
-	0
related	0
differences	0
in	0
the	0
hormonal	0
environment	0
.	0
Pseudoacromegaly	3
induced	0
by	0
the	0
long	0
-	0
term	0
use	0
of	0
minoxidil	1
.	0
Acromegaly	3
is	0
an	0
endocrine	3
disorder	4
caused	0
by	0
chronic	0
excessive	0
growth	0
hormone	0
secretion	0
from	0
the	0
anterior	0
pituitary	0
gland	0
.	0
Significant	0
disfiguring	0
changes	0
occur	0
as	0
a	0
result	0
of	0
bone	0
","	0
cartilage	0
","	0
and	0
soft	0
tissue	0
hypertrophy	3
","	0
including	0
the	0
thickening	0
of	0
the	0
skin	0
","	0
coarsening	0
of	0
facial	0
features	0
","	0
and	0
cutis	3
verticis	4
gyrata	4
.	0
Pseudoacromegaly	3
","	0
on	0
the	0
other	0
hand	0
","	0
is	0
the	0
presence	0
of	0
similar	0
acromegaloid	0
features	0
in	0
the	0
absence	0
of	0
elevated	0
growth	0
hormone	0
or	0
insulin	0
-	0
like	0
growth	0
factor	0
levels	0
.	0
We	0
present	0
a	0
patient	0
with	0
pseudoacromegaly	3
that	0
resulted	0
from	0
the	0
long	0
-	0
term	0
use	0
of	0
minoxidil	1
at	0
an	0
unusually	0
high	0
dose	0
.	0
This	0
is	0
the	0
first	0
case	0
report	0
of	0
pseudoacromegaly	3
as	0
a	0
side	0
effect	0
of	0
minoxidil	1
use	0
.	0
Combined	0
androgen	0
blockade	0
-	0
induced	0
anemia	3
in	0
prostate	3
cancer	4
patients	0
without	0
bone	0
involvement	0
.	0
BACKGR0UND	0
:	0
To	0
determine	0
the	0
onset	0
and	0
extent	0
of	0
combined	0
androgen	0
blockade	0
(	0
CAB	0
)	0
-	0
induced	0
anemia	3
in	0
prostate	3
cancer	4
patients	0
without	0
bone	0
involvement	0
.	0
PATIENTS	0
AND	0
METH0DS	0
:	0
Forty	0
-	0
two	0
patients	0
with	0
biopsy	0
-	0
proven	0
prostatic	3
adenocarcinoma	4
[	0
26	0
with	0
stage	0
C	0
(	0
T3N0M0	0
)	0
and	0
16	0
with	0
stage	0
D1	0
(	0
T3N1M0	0
)	0
]	0
were	0
included	0
in	0
this	0
study	0
.	0
All	0
patients	0
received	0
CAB	0
[	0
leuprolide	1
acetate	2
(	0
LHRH	1
-	2
A	2
)	0
3	0
.	0
75	0
mg	0
","	0
intramuscularly	0
","	0
every	0
28	0
days	0
plus	0
250	0
mg	0
flutamide	1
","	0
tid	0
","	0
per	0
0s	0
]	0
and	0
were	0
evaluated	0
for	0
anemia	3
by	0
physical	0
examination	0
and	0
laboratory	0
tests	0
at	0
baseline	0
and	0
4	0
subsequent	0
intervals	0
(	0
1	0
","	0
2	0
","	0
3	0
and	0
6	0
months	0
post	0
-	0
CAB	0
)	0
.	0
Hb	0
","	0
PSA	0
and	0
Testosterone	1
measurements	0
were	0
recorded	0
.	0
Patients	0
with	0
stage	0
D2	0
-	0
3	0
disease	0
","	0
abnormal	0
hemoglobin	0
level	0
or	0
renal	0
and	0
liver	0
function	0
tests	0
that	0
were	0
higher	0
than	0
the	0
upper	0
limits	0
were	0
excluded	0
from	0
the	0
study	0
.	0
The	0
duration	0
of	0
the	0
study	0
was	0
six	0
months	0
.	0
RESULTS	0
:	0
The	0
mean	0
hemoglobin	0
(	0
Hb	0
)	0
levels	0
were	0
significantly	0
declined	0
in	0
all	0
patients	0
from	0
baseline	0
of	0
14	0
.	0
2	0
g	0
/	0
dl	0
to	0
14	0
.	0
0	0
g	0
/	0
dl	0
","	0
13	0
.	0
5	0
g	0
/	0
dl	0
","	0
13	0
.	0
2	0
g	0
/	0
dl	0
and	0
12	0
.	0
7	0
g	0
/	0
dl	0
at	0
1	0
","	0
2	0
","	0
3	0
and	0
6	0
months	0
post	0
-	0
CAB	0
","	0
respectively	0
.	0
Severe	0
and	0
clinically	0
evident	0
anemia	3
of	0
Hb	0
<	0
11	0
g	0
/	0
dl	0
with	0
clinical	0
symptoms	0
was	0
detected	0
in	0
6	0
patients	0
(	0
14	0
.	0
3	0
%	0
)	0
.	0
This	0
CAB	0
-	0
induced	0
anemia	3
was	0
normochromic	0
and	0
normocytic	0
.	0
At	0
six	0
months	0
post	0
-	0
CAB	0
","	0
patients	0
with	0
severe	0
anemia	3
had	0
a	0
Hb	0
mean	0
value	0
of	0
10	0
.	0
2	0
+	0
/	0
-	0
0	0
.	0
1	0
g	0
/	0
dl	0
(	0
X	0
+	0
/	0
-	0
SE	0
)	0
","	0
whereas	0
the	0
other	0
patients	0
had	0
mild	0
anemia	3
with	0
Hb	0
mean	0
value	0
of	0
13	0
.	0
2	0
+	0
/	0
-	0
0	0
.	0
17	0
(	0
X	0
+	0
/	0
-	0
SE	0
)	0
.	0
The	0
development	0
of	0
severe	0
anemia	3
at	0
6	0
months	0
post	0
-	0
CAB	0
was	0
predictable	0
by	0
the	0
reduction	0
of	0
Hb	0
baseline	0
value	0
of	0
more	0
than	0
2	0
.	0
5	0
g	0
/	0
dl	0
after	0
3	0
months	0
of	0
CAB	0
(	0
p	0
=	0
0	0
.	0
1	0
)	0
.	0
The	0
development	0
of	0
severe	0
CAB	0
-	0
induced	0
anemia	3
in	0
prostate	3
cancer	4
patients	0
did	0
not	0
correlate	0
with	0
T	0
baseline	0
values	0
(	0
T	0
<	0
3	0
ng	0
/	0
ml	0
versus	0
T	0
>	0
or	0
=	0
3	0
ng	0
/	0
ml	0
)	0
","	0
with	0
age	0
(	0
<	0
76	0
yrs	0
versus	0
>	0
or	0
=	0
76	0
yrs	0
)	0
","	0
and	0
clinical	0
stage	0
(	0
stage	0
C	0
versus	0
stage	0
D1	0
)	0
.	0
Severe	0
and	0
clinically	0
evident	0
anemia	3
was	0
easily	0
corrected	0
by	0
subcutaneous	0
injections	0
(	0
3	0
times	0
/	0
week	0
for	0
1	0
month	0
)	0
of	0
recombinant	0
erythropoietin	0
(	0
rHuEP0	0
-	0
beta	0
)	0
.	0
C0NCLUSI0N	0
:	0
0ur	0
data	0
suggest	0
that	0
rHuEP0	0
-	0
beta	0
correctable	0
CAB	0
-	0
induced	0
anemia	3
occurs	0
in	0
14	0
.	0
3	0
%	0
of	0
prostate	3
cancer	4
patients	0
after	0
6	0
months	0
of	0
therapy	0
.	0
Delirium	3
during	0
clozapine	1
treatment	0
:	0
incidence	0
and	0
associated	0
risk	0
factors	0
.	0
BACKGR0UND	0
:	0
Incidence	0
and	0
risk	0
factors	0
for	0
delirium	3
during	0
clozapine	1
treatment	0
require	0
further	0
clarification	0
.	0
METH0DS	0
:	0
We	0
used	0
computerized	0
pharmacy	0
records	0
to	0
identify	0
all	0
adult	0
psychiatric	3
inpatients	0
treated	0
with	0
clozapine	1
(	0
1995	0
-	0
96	0
)	0
","	0
reviewed	0
their	0
medical	0
records	0
to	0
score	0
incidence	0
and	0
severity	0
of	0
delirium	3
","	0
and	0
tested	0
associations	0
with	0
potential	0
risk	0
factors	0
.	0
RESULTS	0
:	0
Subjects	0
(	0
n	0
=	0
139	0
)	0
were	0
72	0
women	0
and	0
67	0
men	0
","	0
aged	0
40	0
.	0
8	0
+	0
/	0
-	0
12	0
.	0
1	0
years	0
","	0
hospitalized	0
for	0
24	0
.	0
9	0
+	0
/	0
-	0
23	0
.	0
3	0
days	0
","	0
and	0
given	0
clozapine	1
","	0
gradually	0
increased	0
to	0
an	0
average	0
daily	0
dose	0
of	0
282	0
+	0
/	0
-	0
203	0
mg	0
(	0
3	0
.	0
45	0
+	0
/	0
-	0
2	0
.	0
45	0
mg	0
/	0
kg	0
)	0
for	0
18	0
.	0
9	0
+	0
/	0
-	0
16	0
.	0
4	0
days	0
.	0
Delirium	3
was	0
diagnosed	0
in	0
14	0
(	0
10	0
.	0
1	0
%	0
incidence	0
","	0
or	0
1	0
.	0
48	0
cases	0
/	0
person	0
-	0
years	0
of	0
exposure	0
)	0
;	0
71	0
.	0
4	0
%	0
of	0
cases	0
were	0
moderate	0
or	0
severe	0
.	0
Associated	0
factors	0
were	0
co	0
-	0
treatment	0
with	0
other	0
centrally	0
antimuscarinic	0
agents	0
","	0
poor	0
clinical	0
outcome	0
","	0
older	0
age	0
","	0
and	0
longer	0
hospitalization	0
(	0
by	0
17	0
.	0
5	0
days	0
","	0
increasing	0
cost	0
)	0
;	0
sex	0
","	0
diagnosis	0
or	0
medical	0
co	0
-	0
morbidity	0
","	0
and	0
daily	0
clozapine	1
dose	0
","	0
which	0
fell	0
with	0
age	0
","	0
were	0
unrelated	0
.	0
C0NCLUSI0NS	0
:	0
Delirium	3
was	0
found	0
in	0
10	0
%	0
of	0
clozapine	1
-	0
treated	0
inpatients	0
","	0
particularly	0
in	0
older	0
patients	0
exposed	0
to	0
other	0
central	0
anticholinergics	0
.	0
Delirium	3
was	0
inconsistently	0
recognized	0
clinically	0
in	0
milder	0
cases	0
and	0
was	0
associated	0
with	0
increased	0
length	0
-	0
of	0
-	0
stay	0
and	0
higher	0
costs	0
","	0
and	0
inferior	0
clinical	0
outcome	0
.	0
Neuroprotective	0
action	0
of	0
MPEP	1
","	0
a	0
selective	0
mGluR5	0
antagonist	0
","	0
in	0
methamphetamine	1
-	0
induced	0
dopaminergic	0
neurotoxicity	3
is	0
associated	0
with	0
a	0
decrease	0
in	0
dopamine	1
outflow	0
and	0
inhibition	0
of	0
hyperthermia	3
in	0
rats	0
.	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
examine	0
the	0
role	0
of	0
metabotropic	0
glutamate	1
receptor	0
5	0
(	0
mGluR5	0
)	0
in	0
the	0
toxic	0
action	0
of	0
methamphetamine	1
on	0
dopaminergic	0
neurones	0
in	0
rats	0
.	0
Methamphetamine	1
(	0
10	0
mg	0
/	0
kg	0
sc	0
)	0
","	0
administered	0
five	0
times	0
","	0
reduced	0
the	0
levels	0
of	0
dopamine	1
and	0
its	0
metabolites	0
in	0
striatal	0
tissue	0
when	0
measured	0
72	0
h	0
after	0
the	0
last	0
injection	0
.	0
A	0
selective	0
antagonist	0
of	0
mGluR5	0
","	0
2	1
-	2
methyl	2
-	2
6	2
-	2
(	2
phenylethynyl	2
)	2
pyridine	2
(	0
MPEP	1
;	0
5	0
mg	0
/	0
kg	0
ip	0
)	0
","	0
when	0
administered	0
five	0
times	0
immediately	0
before	0
each	0
methamphetamine	1
injection	0
reversed	0
the	0
above	0
-	0
mentioned	0
methamphetamine	1
effects	0
.	0
A	0
single	0
MPEP	1
(	0
5	0
mg	0
/	0
kg	0
ip	0
)	0
injection	0
reduced	0
the	0
basal	0
extracellular	0
dopamine	1
level	0
in	0
the	0
striatum	0
","	0
as	0
well	0
as	0
dopamine	1
release	0
stimulated	0
either	0
by	0
methamphetamine	1
(	0
10	0
mg	0
/	0
kg	0
sc	0
)	0
or	0
by	0
intrastriatally	0
administered	0
veratridine	1
(	0
100	0
microM	0
)	0
.	0
Moreover	0
","	0
it	0
transiently	0
diminished	0
the	0
methamphetamine	1
(	0
10	0
mg	0
/	0
kg	0
sc	0
)	0
-	0
induced	0
hyperthermia	3
and	0
reduced	0
basal	0
body	0
temperature	0
.	0
MPEP	1
administered	0
into	0
the	0
striatum	0
at	0
high	0
concentrations	0
(	0
500	0
microM	0
)	0
increased	0
extracellular	0
dopamine	1
levels	0
","	0
while	0
lower	0
concentrations	0
(	0
50	0
-	0
100	0
microM	0
)	0
were	0
devoid	0
of	0
any	0
effect	0
.	0
The	0
results	0
of	0
this	0
study	0
suggest	0
that	0
the	0
blockade	0
of	0
mGluR5	0
by	0
MPEP	1
may	0
protect	0
dopaminergic	0
neurones	0
against	0
methamphetamine	1
-	0
induced	0
toxicity	3
.	0
Neuroprotection	0
rendered	0
by	0
MPEP	1
may	0
be	0
associated	0
with	0
the	0
reduction	0
of	0
the	0
methamphetamine	1
-	0
induced	0
dopamine	1
efflux	0
in	0
the	0
striatum	0
due	0
to	0
the	0
blockade	0
of	0
extrastriatal	0
mGluR5	0
","	0
and	0
with	0
a	0
decrease	0
in	0
hyperthermia	3
.	0
Protective	0
efficacy	0
of	0
neuroactive	0
steroids	1
against	0
cocaine	1
kindled	0
-	0
seizures	3
in	0
mice	0
.	0
Neuroactive	0
steroids	1
demonstrate	0
pharmacological	0
actions	0
that	0
have	0
relevance	0
for	0
a	0
host	0
of	0
neurological	3
and	4
psychiatric	4
disorders	4
.	0
They	0
offer	0
protection	0
against	0
seizures	3
in	0
a	0
range	0
of	0
models	0
and	0
seem	0
to	0
inhibit	0
certain	0
stages	0
of	0
drug	3
dependence	4
in	0
preclinical	0
assessments	0
.	0
The	0
present	0
study	0
was	0
designed	0
to	0
evaluate	0
two	0
endogenous	0
and	0
one	0
synthetic	0
neuroactive	0
steroid	1
that	0
positively	0
modulate	0
the	0
gamma	1
-	2
aminobutyric	2
acid	2
(	0
GABA	1
(	0
A	0
)	0
)	0
receptor	0
against	0
the	0
increase	0
in	0
sensitivity	0
to	0
the	0
convulsant	0
effects	0
of	0
cocaine	1
engendered	0
by	0
repeated	0
cocaine	1
administration	0
(	0
seizure	3
kindling	0
)	0
.	0
Allopregnanolone	1
(	0
3alpha	1
-	2
hydroxy	2
-	2
5alpha	2
-	2
pregnan	2
-	2
20	2
-	2
one	2
)	0
","	0
pregnanolone	1
(	0
3alpha	1
-	2
hydroxy	2
-	2
5beta	2
-	2
pregnan	2
-	2
20	2
-	2
one	2
)	0
and	0
ganaxolone	1
(	0
a	0
synthetic	0
derivative	0
of	0
allopregnanolone	1
3alpha	1
-	2
hydroxy	2
-	2
3beta	2
-	2
methyl	2
-	2
5alpha	2
-	2
pregnan	2
-	2
20	2
-	2
one	2
)	0
were	0
tested	0
for	0
their	0
ability	0
to	0
suppress	0
the	0
expression	0
(	0
anticonvulsant	0
effect	0
)	0
and	0
development	0
(	0
antiepileptogenic	0
effect	0
)	0
of	0
cocaine	1
-	0
kindled	0
seizures	3
in	0
male	0
","	0
Swiss	0
-	0
Webster	0
mice	0
.	0
Kindled	0
seizures	3
were	0
induced	0
by	0
daily	0
administration	0
of	0
60	0
mg	0
/	0
kg	0
cocaine	1
for	0
5	0
days	0
.	0
All	0
of	0
these	0
positive	0
GABA	1
(	0
A	0
)	0
modulators	0
suppressed	0
the	0
expression	0
of	0
kindled	0
seizures	3
","	0
whereas	0
only	0
allopregnanolone	1
and	0
ganaxolone	1
inhibited	0
the	0
development	0
of	0
kindling	0
.	0
Allopregnanolone	1
and	0
pregnanolone	1
","	0
but	0
not	0
ganaxolone	1
","	0
also	0
reduced	0
cumulative	0
lethality	0
associated	0
with	0
kindling	0
.	0
These	0
findings	0
demonstrate	0
that	0
some	0
neuroactive	0
steroids	1
attenuate	0
convulsant	0
and	0
sensitizing	0
properties	0
of	0
cocaine	1
and	0
add	0
to	0
a	0
growing	0
literature	0
on	0
their	0
potential	0
use	0
in	0
the	0
modulation	0
of	0
effects	0
of	0
drugs	0
of	0
abuse	0
.	0
Effect	0
of	0
humoral	0
modulators	0
of	0
morphine	1
-	0
induced	0
increase	3
in	4
locomotor	4
activity	4
of	0
mice	0
.	0
The	0
effect	0
of	0
humoral	0
modulators	0
on	0
the	0
morphine	1
-	0
induced	0
increase	3
in	4
locomotor	4
activity	4
of	0
mice	0
was	0
studied	0
.	0
The	0
subcutaneous	0
administration	0
of	0
10	0
mg	0
/	0
kg	0
of	0
morphine	1
-	0
HC1	0
produced	0
a	0
marked	0
increase	3
in	4
locomotor	4
activity	4
in	0
mice	0
.	0
The	0
morphine	1
-	0
induced	0
hyperactivity	3
was	0
potentiated	0
by	0
scopolamine	1
and	0
attenuated	0
by	0
physostigmine	1
.	0
In	0
contrast	0
","	0
both	0
methscopolamine	1
and	0
neostigmine	1
","	0
which	0
do	0
not	0
penetrate	0
the	0
blood	0
-	0
brain	0
barrier	0
","	0
had	0
no	0
effect	0
on	0
the	0
hyperactivity	3
produced	0
by	0
morphine	1
.	0
Pretreatment	0
of	0
mice	0
with	0
alpha	1
-	2
methyltyrosine	2
(	0
20	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
","	0
one	0
hour	0
)	0
","	0
an	0
inhibitor	0
of	0
tyrosine	1
hydroxylase	0
","	0
significantly	0
decreased	0
the	0
activity	0
-	0
increasing	0
effects	0
of	0
morphine	1
.	0
0n	0
the	0
other	0
hand	0
","	0
pretreatment	0
with	0
p	1
-	2
chlorophenylalamine	2
(	0
3	0
X	0
320	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
","	0
24	0
hr	0
)	0
","	0
a	0
serotonin	1
depletor	0
","	0
caused	0
no	0
significant	0
change	0
in	0
the	0
hyperactivity	3
.	0
The	0
study	0
suggests	0
that	0
the	0
activity	0
-	0
increasing	0
effects	0
of	0
morphine	1
are	0
mediated	0
by	0
the	0
release	0
of	0
catecholamines	1
from	0
adrenergic	0
neurons	0
in	0
the	0
brain	0
.	0
And	0
the	0
results	0
are	0
consistent	0
with	0
the	0
hypothesis	0
that	0
morphine	1
acts	0
by	0
retarding	0
the	0
release	0
of	0
acetylcholine	1
at	0
some	0
central	0
cholinergic	0
synapses	0
.	0
It	0
is	0
also	0
suggested	0
from	0
collected	0
evidence	0
that	0
the	0
activity	0
-	0
increasing	0
effects	0
of	0
morphine	1
in	0
mice	0
are	0
mediated	0
by	0
mechanisms	0
different	0
from	0
those	0
which	0
mediate	0
the	0
activity	0
-	0
increasing	0
effects	0
of	0
morphine	1
in	0
rats	0
.	0
Effects	0
of	0
uninephrectomy	0
and	0
high	0
protein	0
feeding	0
on	0
lithium	1
-	0
induced	0
chronic	3
renal	4
failure	4
in	0
rats	0
.	0
Rats	0
with	0
lithium	1
-	0
induced	0
nephropathy	3
were	0
subjected	0
to	0
high	0
protein	0
(	0
HP	0
)	0
feeding	0
","	0
uninephrectomy	0
(	0
NX	0
)	0
or	0
a	0
combination	0
of	0
these	0
","	0
in	0
an	0
attempt	0
to	0
induce	0
glomerular	0
hyperfiltration	0
and	0
further	0
progression	0
of	0
renal	3
failure	4
.	0
Newborn	0
female	0
Wistar	0
rats	0
were	0
fed	0
a	0
lithium	1
-	0
containing	0
diet	0
(	0
50	0
mmol	0
/	0
kg	0
)	0
for	0
8	0
weeks	0
and	0
then	0
randomized	0
to	0
normal	0
diet	0
","	0
HP	0
diet	0
(	0
40	0
vs	0
.	0
19	0
%	0
)	0
","	0
NX	0
or	0
HP	0
+	0
NX	0
for	0
another	0
8	0
weeks	0
.	0
Corresponding	0
non	0
-	0
lithium	1
pretreated	0
groups	0
were	0
generated	0
.	0
When	0
comparing	0
all	0
lithium	1
treated	0
versus	0
non	0
-	0
lithium	1
-	0
treated	0
groups	0
","	0
lithium	1
caused	0
a	0
reduction	0
in	0
glomerular	0
filtration	0
rate	0
(	0
GFR	0
)	0
without	0
significant	0
changes	0
in	0
effective	0
renal	0
plasma	0
flow	0
(	0
as	0
determined	0
by	0
a	0
marker	0
secreted	0
into	0
the	0
proximal	0
tubules	0
)	0
or	0
lithium	1
clearance	0
.	0
Consequently	0
","	0
lithium	1
pretreatment	0
caused	0
a	0
fall	0
in	0
filtration	0
fraction	0
and	0
an	0
increase	0
in	0
fractional	0
Li	1
excretion	0
.	0
Lithium	1
also	0
caused	0
proteinuria	3
and	0
systolic	0
hypertension	3
in	0
absence	0
of	0
glomerulosclerosis	3
.	0
HP	0
failed	0
to	0
accentuante	0
progression	0
of	0
renal	3
failure	4
and	0
in	0
fact	0
tended	0
to	0
increase	0
GFR	0
and	0
decrease	0
plasma	0
creatinine	1
levels	0
in	0
lithium	1
pretreated	0
rats	0
.	0
NX	0
caused	0
an	0
additive	0
deterioration	0
in	0
GFR	0
which	0
","	0
however	0
","	0
was	0
ameliorated	0
by	0
HP	0
.	0
NX	0
+	0
HP	0
caused	0
a	0
further	0
rise	0
in	0
blood	0
pressure	0
in	0
Li	1
-	0
pretreated	0
rats	0
.	0
The	0
results	0
indicate	0
that	0
Li	1
-	0
induced	0
nephropathy	3
","	0
even	0
when	0
the	0
GFR	0
is	0
only	0
modestly	0
reduced	0
","	0
is	0
associated	0
with	0
proteinuria	3
and	0
arterial	0
systolic	0
hypertension	3
.	0
In	0
this	0
model	0
of	0
chronic	3
renal	4
failure	4
the	0
decline	0
in	0
GFR	0
is	0
not	0
accompanied	0
by	0
a	0
corresponding	0
fall	0
in	0
effective	0
renal	0
plasma	0
flow	0
","	0
which	0
may	0
be	0
the	0
functional	0
expression	0
of	0
the	0
formation	0
of	0
nonfiltrating	0
atubular	0
glomeruli	0
.	0
The	0
fractional	0
reabsorption	0
of	0
tubular	0
fluid	0
by	0
the	0
proximal	0
tubules	0
is	0
reduced	0
","	0
leaving	0
the	0
distal	0
delivery	0
unchanged	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0
Treatment	0
of	0
Crohn	3
'	4
s	4
disease	4
with	0
fusidic	1
acid	2
:	0
an	0
antibiotic	0
with	0
immunosuppressive	0
properties	0
similar	0
to	0
cyclosporin	1
.	0
Fusidic	0
acid	0
is	0
an	0
antibiotic	0
with	0
T	0
-	0
cell	0
specific	0
immunosuppressive	0
effects	0
similar	0
to	0
those	0
of	0
cyclosporin	1
.	0
Because	0
of	0
the	0
need	0
for	0
the	0
development	0
of	0
new	0
treatments	0
for	0
Crohn	3
'	4
s	4
disease	4
","	0
a	0
pilot	0
study	0
was	0
undertaken	0
to	0
estimate	0
the	0
pharmacodynamics	0
and	0
tolerability	0
of	0
fusidic	1
acid	2
treatment	0
in	0
chronic	0
active	0
","	0
therapy	0
-	0
resistant	0
patients	0
.	0
Eight	0
Crohn	3
'	4
s	4
disease	4
patients	0
were	0
included	0
.	0
Fusidic	1
acid	2
was	0
administered	0
orally	0
in	0
a	0
dose	0
of	0
500	0
mg	0
t	0
.	0
d	0
.	0
s	0
.	0
and	0
the	0
treatment	0
was	0
planned	0
to	0
last	0
8	0
weeks	0
.	0
The	0
disease	0
activity	0
was	0
primarily	0
measured	0
by	0
a	0
modified	0
individual	0
grading	0
score	0
.	0
Five	0
of	0
8	0
patients	0
(	0
63	0
%	0
)	0
improved	0
during	0
fusidic	1
acid	2
treatment	0
:	0
3	0
at	0
two	0
weeks	0
and	0
2	0
after	0
four	0
weeks	0
.	0
There	0
were	0
no	0
serious	0
clinical	0
side	0
effects	0
","	0
but	0
dose	0
reduction	0
was	0
required	0
in	0
two	0
patients	0
because	0
of	0
nausea	3
.	0
Biochemically	0
","	0
an	0
increase	0
in	0
alkaline	0
phosphatases	0
was	0
noted	0
in	0
5	0
of	0
8	0
cases	0
(	0
63	0
%	0
)	0
","	0
and	0
the	0
greatest	0
increases	0
were	0
seen	0
in	0
those	0
who	0
had	0
elevated	0
levels	0
prior	0
to	0
treatment	0
.	0
All	0
reversed	0
to	0
pre	0
-	0
treatment	0
levels	0
after	0
cessation	0
of	0
treatment	0
.	0
The	0
results	0
of	0
this	0
pilot	0
study	0
suggest	0
that	0
fusidic	1
acid	2
may	0
be	0
of	0
benefit	0
in	0
selected	0
chronic	0
active	0
Crohn	3
'	4
s	4
disease	4
patients	0
in	0
whom	0
conventional	0
treatment	0
is	0
ineffective	0
.	0
Because	0
there	0
seems	0
to	0
exist	0
a	0
scientific	0
rationale	0
for	0
the	0
use	0
of	0
fusidic	1
acid	2
at	0
the	0
cytokine	0
level	0
in	0
inflammatory	3
bowel	4
disease	4
","	0
we	0
suggest	0
that	0
the	0
role	0
of	0
this	0
treatment	0
should	0
be	0
further	0
investigated	0
.	0
Changes	0
in	0
depressive	3
status	0
associated	0
with	0
topical	0
beta	0
-	0
blockers	0
.	0
Depression	3
and	0
sexual	3
dysfunction	4
have	0
been	0
related	0
to	0
side	0
effects	0
of	0
topical	0
beta	0
-	0
blockers	0
.	0
We	0
performed	0
a	0
preliminary	0
study	0
in	0
order	0
to	0
determine	0
any	0
difference	0
between	0
a	0
non	0
selective	0
beta	0
-	0
blocker	0
(	0
timolol	1
)	0
and	0
a	0
selective	0
beta	0
-	0
blocker	0
(	0
betaxolol	1
)	0
regarding	0
CNS	0
side	0
effects	0
.	0
Eight	0
glaucomatous	3
patients	0
chronically	0
treated	0
with	0
timolol	1
0	0
.	0
5	0
%	0
/	0
12h	0
","	0
suffering	0
from	0
depression	3
diagnosed	0
through	0
DMS	0
-	0
III	0
-	0
R	0
criteria	0
","	0
were	0
included	0
in	0
the	0
study	0
.	0
During	0
the	0
six	0
-	0
month	0
follow	0
up	0
","	0
depression	3
was	0
quantified	0
through	0
the	0
Beck	0
and	0
Zung	0
-	0
Conde	0
scales	0
every	0
two	0
months	0
.	0
In	0
a	0
double	0
blind	0
cross	0
-	0
over	0
study	0
with	0
control	0
group	0
","	0
the	0
patients	0
under	0
timolol	1
treatment	0
presented	0
higher	0
depression	3
values	0
measured	0
through	0
the	0
Beck	0
and	0
the	0
Zung	0
-	0
Conde	0
scales	0
(	0
p	0
<	0
0	0
.	0
1	0
vs	0
control	0
)	0
.	0
These	0
results	0
suggest	0
that	0
betaxolol	1
could	0
be	0
less	0
of	0
a	0
depression	3
-	0
inducer	0
than	0
timolol	1
in	0
predisposed	0
patients	0
.	0
Protection	0
against	0
amphetamine	1
-	0
induced	0
neurotoxicity	3
toward	0
striatal	0
dopamine	1
neurons	0
in	0
rodents	0
by	0
LY274614	1
","	0
an	0
excitatory	0
amino	1
acid	2
antagonist	0
.	0
LY274614	1
","	0
3SR	1
","	2
4aRS	2
","	2
6SR	2
","	2
8aRS	2
-	2
6	2
-	2
[	2
phosphonomethyl	2
]	2
decahydr	2
oisoquinoline	2
-	2
3	2
-	2
carboxylic	2
acid	2
","	0
has	0
been	0
described	0
as	0
a	0
potent	0
antagonist	0
of	0
the	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
(	0
NMDA	1
)	0
subtype	0
of	0
glutamate	1
receptor	0
.	0
Here	0
its	0
ability	0
to	0
antagonize	0
the	0
prolonged	0
depletion	0
of	0
dopamine	1
in	0
the	0
striatum	0
by	0
amphetamine	1
in	0
iprindole	1
-	0
treated	0
rats	0
is	0
reported	0
.	0
A	0
single	0
18	0
.	0
4	0
mg	0
/	0
kg	0
(	0
i	0
.	0
p	0
.	0
)	0
dose	0
of	0
(	0
+	0
/	0
-	0
)	0
-	0
amphetamine	1
hemisulfate	0
","	0
given	0
to	0
rats	0
pretreated	0
with	0
iprindole	1
","	0
resulted	0
in	0
persistent	0
depletion	0
of	0
dopamine	1
in	0
the	0
striatum	0
1	0
week	0
later	0
.	0
This	0
prolonged	0
depletion	0
of	0
dopamine	1
in	0
the	0
striatum	0
was	0
antagonized	0
by	0
dizocilpine	1
(	0
MK	1
-	2
801	2
","	0
a	0
non	0
-	0
competitive	0
antagonist	0
of	0
NMDA	1
receptors	0
)	0
or	0
by	0
LY274614	1
(	0
a	0
competitive	0
antagonist	0
of	0
NMDA	1
receptors	0
)	0
.	0
The	0
protective	0
effect	0
of	0
LY274614	1
was	0
dose	0
-	0
dependent	0
","	0
being	0
maximum	0
at	0
10	0
-	0
40	0
mgkg	0
(	0
i	0
.	0
p	0
.	0
)	0
.	0
A	0
10	0
mg	0
/	0
kg	0
dose	0
of	0
LY274614	1
was	0
effective	0
in	0
antagonizing	0
the	0
depletion	0
of	0
dopamine	1
in	0
the	0
striatum	0
","	0
when	0
given	0
as	0
long	0
as	0
8	0
hr	0
prior	0
to	0
amphetamine	1
but	0
not	0
when	0
given	0
24	0
hr	0
prior	0
to	0
amphetamine	1
.	0
Depletion	0
of	0
dopamine	1
in	0
the	0
striatum	0
was	0
also	0
antagonized	0
when	0
LY274614	1
was	0
given	0
after	0
the	0
injection	0
of	0
amphetamine	1
;	0
LY274614	1
protected	0
when	0
given	0
up	0
to	0
4	0
hr	0
after	0
but	0
not	0
when	0
given	0
8	0
or	0
24	0
hr	0
after	0
amphetamine	1
.	0
The	0
prolonged	0
depletion	0
of	0
dopamine	1
in	0
the	0
striatum	0
in	0
mice	0
","	0
given	0
multiple	0
injections	0
of	0
methamphetamine	1
","	0
was	0
also	0
antagonized	0
dose	0
-	0
dependently	0
and	0
completely	0
by	0
LY274614	1
.	0
The	0
data	0
strengthen	0
the	0
evidence	0
that	0
the	0
neurotoxic	3
effect	0
of	0
amphetamine	1
and	0
related	0
compounds	0
toward	0
nigrostriatal	0
dopamine	1
neurons	0
involves	0
NMDA	1
receptors	0
and	0
that	0
LY274614	1
is	0
an	0
NMDA	1
receptor	0
antagonist	0
with	0
long	0
-	0
lasting	0
in	0
vivo	0
effects	0
in	0
rats	0
.	0
Ketoconazole	1
-	0
induced	0
neurologic	3
sequelae	4
.	0
A	0
77	0
-	0
y	0
-	0
old	0
patient	0
developed	0
weakness	3
of	4
extremities	4
","	0
legs	3
paralysis	4
","	0
dysarthria	3
and	0
tremor	3
1	0
h	0
after	0
ingestion	0
of	0
200	0
mg	0
ketoconazole	1
for	0
the	0
first	0
time	0
in	0
his	0
life	0
.	0
All	0
complaints	0
faded	0
away	0
within	0
24	0
h	0
.	0
Few	0
days	0
later	0
","	0
the	0
patient	0
used	0
another	0
200	0
mg	0
ketoconazole	1
tablet	0
","	0
and	0
within	0
an	0
hour	0
experienced	0
a	0
similar	0
clinical	0
picture	0
","	0
which	0
resolved	0
again	0
spontaneously	0
within	0
hours	0
.	0
Laboratory	0
evaluations	0
","	0
including	0
head	0
CT	0
scan	0
","	0
were	0
normal	0
.	0
This	0
case	0
illustrates	0
the	0
need	0
for	0
close	0
vigilance	0
in	0
adverse	3
drug	4
reactions	4
","	0
particularly	0
in	0
the	0
elderly	0
.	0
Development	0
of	0
levodopa	1
-	0
induced	0
dyskinesias	3
in	0
parkinsonian	3
monkeys	0
may	0
depend	0
upon	0
rate	0
of	0
symptom	0
onset	0
and	0
/	0
or	0
duration	0
of	0
symptoms	0
.	0
Levodopa	1
-	0
induced	0
dyskinesias	3
(	0
LIDs	3
)	0
present	0
a	0
major	0
problem	0
for	0
the	0
long	0
-	0
term	0
management	0
of	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
patients	0
.	0
Due	0
to	0
the	0
interdependence	0
of	0
risk	0
factors	0
in	0
clinical	0
populations	0
","	0
it	0
is	0
difficult	0
to	0
independently	0
examine	0
factors	0
that	0
may	0
influence	0
the	0
development	0
of	0
LIDs	3
.	0
Using	0
macaque	0
monkeys	0
with	0
different	0
types	0
of	0
MPTP	1
-	0
induced	0
parkinsonism	3
","	0
the	0
current	0
study	0
evaluated	0
the	0
degree	0
to	0
which	0
rate	0
of	0
symptom	0
progression	0
","	0
symptom	0
severity	0
","	0
and	0
response	0
to	0
and	0
duration	0
of	0
levodopa	1
therapy	0
may	0
be	0
involved	0
in	0
the	0
development	0
of	0
LIDs	3
.	0
Monkeys	0
with	0
acute	0
(	0
short	0
-	0
term	0
)	0
MPTP	1
exposure	0
","	0
rapid	0
symptom	0
onset	0
and	0
short	0
symptom	0
duration	0
prior	0
to	0
initiation	0
of	0
levodopa	1
therapy	0
developed	0
dyskinesia	3
between	0
11	0
and	0
24	0
days	0
of	0
daily	0
levodopa	1
administration	0
.	0
In	0
contrast	0
","	0
monkeys	0
with	0
long	0
-	0
term	0
MPTP	1
exposure	0
","	0
slow	0
symptom	0
progression	0
and	0
/	0
or	0
long	0
symptom	0
duration	0
prior	0
to	0
initiation	0
of	0
levodopa	1
therapy	0
were	0
more	0
resistant	0
to	0
developing	0
LIDs	3
(	0
e	0
.	0
g	0
.	0
","	0
dyskinesia	3
developed	0
no	0
sooner	0
than	0
146	0
days	0
of	0
chronic	0
levodopa	1
administration	0
)	0
.	0
All	0
animals	0
were	0
similarly	0
symptomatic	0
at	0
the	0
start	0
of	0
levodopa	1
treatment	0
and	0
had	0
similar	0
therapeutic	0
responses	0
to	0
the	0
drug	0
.	0
These	0
data	0
suggest	0
distinct	0
differences	0
in	0
the	0
propensity	0
to	0
develop	0
LIDs	3
in	0
monkeys	0
with	0
different	0
rates	0
of	0
symptom	0
progression	0
or	0
symptom	0
durations	0
prior	0
to	0
levodopa	1
and	0
demonstrate	0
the	0
value	0
of	0
these	0
models	0
for	0
further	0
studying	0
the	0
pathophysiology	0
of	0
LIDs	3
.	0
A	0
diet	0
promoting	0
sugar	3
dependency	4
causes	0
behavioral	3
cross	4
-	4
sensitization	4
to	0
a	0
low	0
dose	0
of	0
amphetamine	1
.	0
Previous	0
research	0
in	0
this	0
laboratory	0
has	0
shown	0
that	0
a	0
diet	0
of	0
intermittent	0
excessive	0
sugar	0
consumption	0
produces	0
a	0
state	0
with	0
neurochemical	0
and	0
behavioral	0
similarities	0
to	0
drug	3
dependency	4
.	0
The	0
present	0
study	0
examined	0
whether	0
female	0
rats	0
on	0
various	0
regimens	0
of	0
sugar	0
access	0
would	0
show	0
behavioral	3
cross	4
-	4
sensitization	4
to	0
a	0
low	0
dose	0
of	0
amphetamine	1
.	0
After	0
a	0
30	0
-	0
min	0
baseline	0
measure	0
of	0
locomotor	0
activity	0
(	0
day	0
0	0
)	0
","	0
animals	0
were	0
maintained	0
on	0
a	0
cyclic	0
diet	0
of	0
12	0
-	0
h	0
deprivation	0
followed	0
by	0
12	0
-	0
h	0
access	0
to	0
10	0
%	0
sucrose	1
solution	0
and	0
chow	0
pellets	0
(	0
12	0
h	0
access	0
starting	0
4	0
h	0
after	0
onset	0
of	0
the	0
dark	0
period	0
)	0
for	0
21	0
days	0
.	0
Locomotor	0
activity	0
was	0
measured	0
again	0
for	0
30	0
min	0
at	0
the	0
beginning	0
of	0
days	0
1	0
and	0
21	0
of	0
sugar	0
access	0
.	0
Beginning	0
on	0
day	0
22	0
","	0
all	0
rats	0
were	0
maintained	0
on	0
ad	0
libitum	0
chow	0
.	0
Nine	0
days	0
later	0
locomotor	0
activity	0
was	0
measured	0
in	0
response	0
to	0
a	0
single	0
low	0
dose	0
of	0
amphetamine	1
(	0
0	0
.	0
5	0
mg	0
/	0
kg	0
)	0
.	0
The	0
animals	0
that	0
had	0
experienced	0
cyclic	0
sucrose	1
and	0
chow	0
were	0
hyperactive	3
in	0
response	0
to	0
amphetamine	1
compared	0
with	0
four	0
control	0
groups	0
(	0
ad	0
libitum	0
10	0
%	0
sucrose	1
and	0
chow	0
followed	0
by	0
amphetamine	1
injection	0
","	0
cyclic	0
chow	0
followed	0
by	0
amphetamine	1
injection	0
","	0
ad	0
libitum	0
chow	0
with	0
amphetamine	1
","	0
or	0
cyclic	0
10	0
%	0
sucrose	1
and	0
chow	0
with	0
a	0
saline	0
injection	0
)	0
.	0
These	0
results	0
suggest	0
that	0
a	0
diet	0
comprised	0
of	0
alternating	0
deprivation	0
and	0
access	0
to	0
a	0
sugar	0
solution	0
and	0
chow	0
produces	0
bingeing	0
on	0
sugar	0
that	0
leads	0
to	0
a	0
long	0
lasting	0
state	0
of	0
increased	0
sensitivity	0
to	0
amphetamine	1
","	0
possibly	0
due	0
to	0
a	0
lasting	0
alteration	0
in	0
the	0
dopamine	1
system	0
.	0
Reversible	0
dilated	3
cardiomyopathy	4
related	0
to	0
amphotericin	1
B	2
therapy	0
.	0
We	0
describe	0
a	0
patient	0
who	0
developed	0
dilated	3
cardiomyopathy	4
and	0
clinical	0
congestive	0
heart	3
failure	4
after	0
2	0
months	0
of	0
therapy	0
with	0
amphotericin	1
B	2
(	0
AmB	1
)	0
for	0
disseminated	0
coccidioidomycosis	3
.	0
His	0
echocardiographic	0
abnormalities	0
and	0
heart	3
failure	4
resolved	0
after	0
posaconazole	1
was	0
substituted	0
for	0
AmB	1
.	0
It	0
is	0
important	0
to	0
recognize	0
the	0
rare	0
and	0
potentially	0
reversible	0
toxicity	3
of	0
AmB	1
.	0
N0	1
-	0
induced	0
migraine	3
attack	0
:	0
strong	0
increase	0
in	0
plasma	0
calcitonin	1
gene	2
-	2
related	2
peptide	2
(	0
CGRP	1
)	0
concentration	0
and	0
negative	0
correlation	0
with	0
platelet	0
serotonin	1
release	0
.	0
The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
investigate	0
changes	0
in	0
the	0
plasma	0
calcitonin	1
gene	2
-	2
related	2
peptide	2
(	0
CGRP	1
)	0
concentration	0
and	0
platelet	0
serotonin	1
(	0
5	1
-	2
hydroxytriptamine	2
","	0
5	1
-	2
HT	2
)	0
content	0
during	0
the	0
immediate	0
headache	3
and	0
the	0
delayed	0
genuine	0
migraine	3
attack	0
provoked	0
by	0
nitroglycerin	1
.	0
Fifteen	0
female	0
migraineurs	3
(	4
without	4
aura	4
)	4
and	0
eight	0
controls	0
participated	0
in	0
the	0
study	0
.	0
Sublingual	0
nitroglycerin	1
(	0
0	0
.	0
5	0
mg	0
)	0
was	0
administered	0
.	0
Blood	0
was	0
collected	0
from	0
the	0
antecubital	0
vein	0
four	0
times	0
:	0
60	0
min	0
before	0
and	0
after	0
the	0
nitroglycerin	1
application	0
","	0
and	0
60	0
and	0
120	0
min	0
after	0
the	0
beginning	0
of	0
the	0
migraine	3
attack	0
(	0
mean	0
344	0
and	0
404	0
min	0
;	0
12	0
subjects	0
)	0
.	0
In	0
those	0
subjects	0
who	0
had	0
no	0
migraine	3
attack	0
(	0
11	0
subjects	0
)	0
a	0
similar	0
time	0
schedule	0
was	0
used	0
.	0
Plasma	0
CGRP	1
concentration	0
increased	0
significantly	0
(	0
P	0
<	0
0	0
.	0
1	0
)	0
during	0
the	0
migraine	3
attack	0
and	0
returned	0
to	0
baseline	0
after	0
the	0
cessation	0
of	0
the	0
migraine	3
.	0
In	0
addition	0
","	0
both	0
change	0
and	0
peak	0
","	0
showed	0
significant	0
positive	0
correlations	0
with	0
migraine	3
headache	3
intensity	0
(	0
P	0
<	0
0	0
.	0
1	0
)	0
.	0
However	0
","	0
plasma	0
CGRP	1
concentrations	0
failed	0
to	0
change	0
during	0
immediate	0
headache	3
and	0
in	0
the	0
subjects	0
with	0
no	0
migraine	3
attack	0
.	0
Basal	0
CGRP	1
concentration	0
was	0
significantly	0
higher	0
and	0
platelet	0
5	1
-	2
HT	2
content	0
tended	0
to	0
be	0
lower	0
in	0
subjects	0
who	0
experienced	0
a	0
migraine	3
attack	0
.	0
Platelet	0
serotonin	1
content	0
decreased	0
significantly	0
(	0
P	0
<	0
0	0
.	0
1	0
)	0
after	0
nitroglycerin	1
in	0
subjects	0
with	0
no	0
migraine	3
attack	0
but	0
no	0
consistent	0
change	0
was	0
observed	0
in	0
patients	0
with	0
migraine	3
attack	0
.	0
In	0
conclusion	0
","	0
the	0
fact	0
that	0
plasma	0
CGRP	1
concentration	0
correlates	0
with	0
the	0
timing	0
and	0
severity	0
of	0
a	0
migraine	3
headache	3
suggests	0
a	0
direct	0
relationship	0
between	0
CGRP	1
and	0
migraine	3
.	0
In	0
contrast	0
","	0
serotonin	1
release	0
from	0
platelets	0
does	0
not	0
provoke	0
migraine	3
","	0
it	0
may	0
even	0
counteract	0
the	0
headache	3
and	0
the	0
concomitant	0
CGRP	1
release	0
in	0
this	0
model	0
.	0
Hyperbaric	0
oxygen	1
therapy	0
for	0
control	0
of	0
intractable	0
cyclophosphamide	1
-	0
induced	0
hemorrhagic	3
cystitis	4
.	0
We	0
report	0
a	0
case	0
of	0
intractable	0
hemorrhagic	3
cystitis	4
due	0
to	0
cyclophosphamide	1
therapy	0
for	0
Wegener	3
'	4
s	4
granulomatosis	4
.	0
Conservative	0
treatment	0
","	0
including	0
bladder	0
irrigation	0
with	0
physiological	0
saline	0
and	0
instillation	0
of	0
prostaglandin	1
F2	2
alpha	2
","	0
failed	0
to	0
totally	0
control	0
hemorrhage	3
.	0
We	0
then	0
used	0
hyperbaric	0
oxygen	1
at	0
an	0
absolute	0
pressure	0
of	0
2	0
atm	0
","	0
5	0
days	0
a	0
week	0
for	0
8	0
consecutive	0
weeks	0
.	0
The	0
bleeding	3
ceased	0
completely	0
by	0
the	0
end	0
of	0
treatment	0
and	0
the	0
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of	0
hematuria	3
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.	0
No	0
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effect	0
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noted	0
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the	0
course	0
of	0
therapy	0
.	0
In	0
future	0
","	0
this	0
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of	0
therapy	0
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a	0
safe	0
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the	0
treatment	0
of	0
cyclophosphamide	1
-	0
induced	0
hemorrhagic	3
cystitis	4
.	0
Acute	3
psychosis	4
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to	0
treatment	0
with	0
phenytoin	1
in	0
a	0
nonepileptic	0
patient	0
.	0
The	0
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psychosis	3
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usually	0
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the	0
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the	0
epileptic	3
brain	0
substratum	0
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the	0
antiepileptic	0
drugs	0
.	0
The	0
case	0
of	0
a	0
nonepileptic	0
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following	0
phenytoin	1
treatment	0
for	0
trigeminal	3
neuralgia	4
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described	0
.	0
This	0
case	0
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that	0
the	0
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that	0
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phenytoin	1
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in	0
some	0
epileptic	3
patients	0
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the	0
direct	0
result	0
of	0
medication	0
","	0
unrelated	0
to	0
seizures	3
.	0
Risks	0
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the	0
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of	0
beverages	0
containing	0
quinine	1
.	0
Although	0
the	0
United	0
States	0
Food	0
and	0
Drug	0
Administration	0
banned	0
its	0
use	0
for	0
nocturnal	3
leg	4
cramps	4
due	0
to	0
lack	0
of	0
safety	0
and	0
efficacy	0
","	0
quinine	1
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widely	0
available	0
in	0
beverages	0
including	0
tonic	0
water	0
and	0
bitter	0
lemon	0
.	0
Numerous	0
anecdotal	0
reports	0
suggest	0
that	0
products	0
containing	0
quinine	1
may	0
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neurological	3
complications	4
","	0
including	0
confusion	3
","	0
altered	0
mental	0
status	0
","	0
seizures	3
","	0
and	0
coma	3
","	0
particularly	0
in	0
older	0
women	0
.	0
Psychologists	0
need	0
to	0
inquire	0
about	0
consumption	0
of	0
quinine	1
-	0
containing	0
beverages	0
as	0
part	0
of	0
an	0
evaluation	0
process	0
.	0
Transient	0
platypnea	3
-	4
orthodeoxia	4
-	4
like	4
syndrome	4
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by	0
propafenone	1
overdose	3
in	0
a	0
young	0
woman	0
with	0
Ebstein	3
'	4
s	4
anomaly	4
.	0
In	0
this	0
report	0
we	0
describe	0
the	0
case	0
of	0
a	0
37	0
-	0
year	0
-	0
old	0
white	0
woman	0
with	0
Ebstein	3
'	4
s	4
anomaly	4
","	0
who	0
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a	0
rare	0
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called	0
platypnea	3
-	4
orthodeoxia	4
","	0
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massive	0
right	0
-	0
to	0
-	0
left	0
interatrial	0
shunting	0
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transient	0
profound	0
hypoxia	3
and	0
cyanosis	3
.	0
This	0
shunt	0
of	0
blood	0
via	0
a	0
patent	3
foramen	4
ovale	4
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in	0
the	0
presence	0
of	0
a	0
normal	0
pulmonary	0
artery	0
pressure	0
","	0
and	0
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probably	0
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by	0
a	0
propafenone	1
overdose	3
.	0
This	0
drug	0
caused	0
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dysfunction	4
","	0
due	0
to	0
its	0
negative	0
inotropic	0
effect	0
","	0
and	0
hypotension	3
","	0
due	0
to	0
its	0
peripheral	0
vasodilatory	0
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.	0
These	0
effects	0
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rise	0
to	0
an	0
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the	0
right	0
atrial	0
pressure	0
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a	0
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the	0
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one	0
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a	0
consequent	0
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of	0
the	0
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ovale	0
and	0
the	0
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of	0
massive	0
right	0
-	0
to	0
-	0
left	0
shunting	0
.	0
In	0
our	0
case	0
this	0
interatrial	0
shunt	0
was	0
very	0
accurately	0
detected	0
at	0
bubble	0
contrast	0
echocardiography	0
.	0
Noxious	0
chemical	0
stimulation	0
of	0
rat	0
facial	0
mucosa	0
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intracranial	0
blood	0
flow	0
through	0
a	0
trigemino	0
-	0
parasympathetic	0
reflex	0
-	0
-	0
an	0
experimental	0
model	0
for	0
vascular	3
dysfunctions	4
in	0
cluster	3
headache	4
.	0
Cluster	3
headache	4
is	0
characterized	0
by	0
typical	0
autonomic	0
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including	0
facial	0
and	0
intracranial	3
vascular	4
disturbances	4
.	0
Both	0
the	0
trigeminal	0
and	0
the	0
cranial	0
parasympathetic	0
systems	0
may	0
be	0
involved	0
in	0
mediating	0
these	0
dysfunctions	0
.	0
An	0
experimental	0
model	0
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in	0
the	0
rat	0
to	0
measure	0
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in	0
lacrimation	0
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intracranial	0
blood	0
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following	0
noxious	0
chemical	0
stimulation	0
of	0
facial	0
mucosa	0
.	0
Blood	0
flow	0
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in	0
arteries	0
of	0
the	0
exposed	0
cranial	0
dura	0
mater	0
and	0
the	0
parietal	0
cortex	0
using	0
laser	0
Doppler	0
flowmetry	0
.	0
Capsaicin	1
(	0
0	0
.	0
1	0
-	0
1	0
mm	0
)	0
applied	0
to	0
oral	0
or	0
nasal	0
mucosa	0
induced	0
increases	3
in	4
dural	4
and	4
cortical	4
blood	4
flow	4
and	0
provoked	0
lacrimation	0
.	0
These	0
responses	0
were	0
blocked	0
by	0
systemic	0
pre	0
-	0
administration	0
of	0
hexamethonium	1
chloride	2
(	0
20	0
mg	0
/	0
kg	0
)	0
.	0
The	0
evoked	0
increases	3
in	4
dural	4
blood	4
flow	4
were	0
also	0
abolished	0
by	0
topical	0
pre	0
-	0
administration	0
of	0
atropine	1
(	0
1	0
mm	0
)	0
and	0
[	0
Lys1	0
","	0
Pro2	0
","	0
5	0
","	0
Arg3	0
","	0
4	0
","	0
Tyr6	0
]	0
-	0
VIP	0
(	0
0	0
.	0
1	0
mm	0
)	0
","	0
a	0
vasoactive	0
intestinal	0
polypeptide	0
(	0
VIP	0
)	0
antagonist	0
","	0
onto	0
the	0
exposed	0
dura	0
mater	0
.	0
We	0
conclude	0
that	0
noxious	0
stimulation	0
of	0
facial	0
mucosa	0
increases	0
intracranial	0
blood	0
flow	0
and	0
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via	0
a	0
trigemino	0
-	0
parasympathetic	0
reflex	0
.	0
The	0
blood	0
flow	0
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seem	0
to	0
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mediated	0
by	0
the	0
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of	0
acetylcholine	1
and	0
VIP	0
within	0
the	0
meninges	0
.	0
Similar	0
mechanisms	0
may	0
be	0
involved	0
in	0
the	0
pathogenesis	0
of	0
cluster	3
headache	4
.	0
0rganophosphate	1
-	0
induced	0
convulsions	3
and	0
prevention	0
of	0
neuropathological	3
damages	4
.	0
Such	0
organophosphorus	1
(	0
0P	1
)	0
compounds	0
as	0
diisopropylfluorophosphate	1
(	0
DFP	1
)	0
","	0
sarin	1
and	0
soman	1
are	0
potent	0
inhibitors	0
of	0
acetylcholinesterases	0
(	0
AChEs	0
)	0
and	0
butyrylcholinesterases	0
(	0
BChEs	0
)	0
.	0
The	0
acute	0
toxicity	3
of	0
0Ps	1
is	0
the	0
result	0
of	0
their	0
irreversible	0
binding	0
with	0
AChEs	0
in	0
the	0
central	0
nervous	0
system	0
(	0
CNS	0
)	0
","	0
which	0
elevates	0
acetylcholine	1
(	0
ACh	1
)	0
levels	0
.	0
The	0
protective	0
action	0
of	0
subcutaneously	0
(	0
SC	0
)	0
administered	0
antidotes	0
or	0
their	0
combinations	0
in	0
DFP	1
(	0
2	0
.	0
0	0
mg	0
/	0
kg	0
BW	0
)	0
intoxication	0
was	0
studied	0
in	0
9	0
-	0
10	0
-	0
weeks	0
-	0
old	0
Han	0
-	0
Wistar	0
male	0
rats	0
.	0
The	0
rats	0
received	0
AChE	0
reactivator	0
pralidoxime	1
-	2
2	2
-	2
chloride	2
(	0
2PAM	1
)	0
(	0
30	0
.	0
0	0
mg	0
/	0
kg	0
BW	0
)	0
","	0
anticonvulsant	0
diazepam	1
(	0
2	0
.	0
0	0
mg	0
/	0
kg	0
BW	0
)	0
","	0
A	0
(	0
1	0
)	0
-	0
adenosine	1
receptor	0
agonist	0
N	1
(	2
6	2
)	2
-	2
cyclopentyl	2
adenosine	2
(	0
CPA	1
)	0
(	0
2	0
.	0
0	0
mg	0
/	0
kg	0
BW	0
)	0
","	0
NMDA	1
-	0
receptor	0
antagonist	0
dizocilpine	1
maleate	2
(	0
+	0
-	0
MK801	0
hydrogen	0
maleate	0
)	0
(	0
2	0
.	0
0	0
mg	0
/	0
kg	0
BW	0
)	0
or	0
their	0
combinations	0
with	0
cholinolytic	0
drug	0
atropine	1
sulfate	2
(	0
50	0
.	0
0	0
mg	0
/	0
kg	0
BW	0
)	0
immediately	0
or	0
30	0
min	0
after	0
the	0
single	0
SC	0
injection	0
of	0
DFP	1
.	0
The	0
control	0
rats	0
received	0
atropine	1
sulfate	2
","	0
but	0
also	0
saline	0
and	0
olive	0
oil	0
instead	0
of	0
other	0
antidotes	0
and	0
DFP	1
","	0
respectively	0
.	0
All	0
rats	0
were	0
terminated	0
either	0
24	0
h	0
or	0
3	0
weeks	0
after	0
the	0
DFP	1
injection	0
.	0
The	0
rats	0
treated	0
with	0
DFP	1
-	0
atropine	1
showed	0
severe	0
typical	0
0P	1
-	0
induced	0
toxicity	3
signs	0
.	0
When	0
CPA	1
","	0
diazepam	1
or	0
2PAM	1
was	0
given	0
immediately	0
after	0
DFP	1
-	0
atropine	1
","	0
these	0
treatments	0
prevented	0
","	0
delayed	0
or	0
shortened	0
the	0
occurrence	0
of	0
serious	0
signs	0
of	0
poisoning	3
.	0
Atropine	1
-	0
MK801	1
did	0
not	0
offer	0
any	0
additional	0
protection	0
against	0
DFP	1
toxicity	3
.	0
In	0
conclusion	0
","	0
CPA	1
","	0
diazepam	1
and	0
2PAM	1
in	0
combination	0
with	0
atropine	1
prevented	0
the	0
occurrence	0
of	0
serious	0
signs	0
of	0
poisoning	3
and	0
thus	0
reduced	0
the	0
toxicity	3
of	0
DFP	1
in	0
rat	0
.	0
A	0
pyridoxine	1
-	0
dependent	0
behavioral	3
disorder	4
unmasked	0
by	0
isoniazid	1
.	0
A	0
3	0
-	0
year	0
-	0
old	0
girl	0
had	0
behavioral	3
deterioration	4
","	0
with	0
hyperkinesis	3
","	0
irritability	3
","	0
and	0
sleeping	3
difficulties	4
after	0
the	0
therapeutic	0
administration	0
of	0
isoniazid	1
.	0
The	0
administration	0
of	0
pharmacologic	0
doses	0
of	0
pyridoxine	1
hydrochloride	2
led	0
to	0
a	0
disappearance	0
of	0
symptoms	0
.	0
After	0
discontinuing	0
isoniazid	1
therapy	0
a	0
similar	0
pattern	0
of	0
behavior	0
was	0
noted	0
that	0
was	0
controlled	0
by	0
pyridoxine	1
.	0
A	0
placebo	0
had	0
no	0
effect	0
","	0
but	0
niacinamide	1
was	0
as	0
effective	0
as	0
pyridoxine	1
.	0
Periodic	0
withdrawal	0
of	0
pyridoxine	1
was	0
associated	0
with	0
return	0
of	0
the	0
hyperkinesis	3
.	0
The	0
level	0
of	0
pyridoxal	1
in	0
the	0
blood	0
was	0
normal	0
during	0
the	0
periods	0
of	0
relapse	0
.	0
Metabolic	0
studies	0
suggested	0
a	0
block	0
in	0
the	0
kynurenine	1
pathway	0
of	0
tryptophan	1
metabolism	0
.	0
The	0
patient	0
has	0
been	0
followed	0
for	0
six	0
years	0
and	0
has	0
required	0
pharmacologic	0
doses	0
of	0
pyridoxine	1
to	0
control	0
her	0
behavior	0
.	0
Recurrent	0
excitation	0
in	0
the	0
dentate	0
gyrus	0
of	0
a	0
murine	0
model	0
of	0
temporal	3
lobe	4
epilepsy	4
.	0
Similar	0
to	0
rats	0
","	0
systemic	0
pilocarpine	1
injection	0
causes	0
status	3
epilepticus	4
(	0
SE	3
)	0
and	0
the	0
eventual	0
development	0
of	0
spontaneous	0
seizures	3
and	0
mossy	0
fiber	0
sprouting	0
in	0
C57BL	0
/	0
6	0
and	0
CD1	0
mice	0
","	0
but	0
the	0
physiological	0
correlates	0
of	0
these	0
events	0
have	0
not	0
been	0
identified	0
in	0
mice	0
.	0
Population	0
responses	0
in	0
granule	0
cells	0
of	0
the	0
dentate	0
gyrus	0
were	0
examined	0
in	0
transverse	0
slices	0
of	0
the	0
ventral	0
hippocampus	0
from	0
pilocarpine	1
-	0
treated	0
and	0
untreated	0
mice	0
.	0
In	0
Mg	1
(	0
2	0
+	0
)	0
-	0
free	0
bathing	0
medium	0
containing	0
bicuculline	1
","	0
conditions	0
designed	0
to	0
increase	0
excitability	0
in	0
the	0
slices	0
","	0
electrical	0
stimulation	0
of	0
the	0
hilus	0
resulted	0
in	0
a	0
single	0
population	0
spike	0
in	0
granule	0
cells	0
from	0
control	0
mice	0
and	0
pilocarpine	1
-	0
treated	0
mice	0
that	0
did	0
not	0
experience	0
SE	3
.	0
In	0
SE	3
survivors	0
","	0
similar	0
stimulation	0
resulted	0
in	0
a	0
population	0
spike	0
followed	0
","	0
at	0
a	0
variable	0
latency	0
","	0
by	0
negative	0
DC	0
shifts	0
and	0
repetitive	0
afterdischarges	0
of	0
3	0
-	0
60	0
s	0
duration	0
","	0
which	0
were	0
blocked	0
by	0
ionotropic	0
glutamate	1
receptor	0
antagonists	0
.	0
Focal	0
glutamate	1
photostimulation	0
of	0
the	0
granule	0
cell	0
layer	0
at	0
sites	0
distant	0
from	0
the	0
recording	0
pipette	0
resulted	0
in	0
population	0
responses	0
of	0
1	0
-	0
30	0
s	0
duration	0
in	0
slices	0
from	0
SE	3
survivors	0
but	0
not	0
other	0
groups	0
.	0
These	0
data	0
support	0
the	0
hypothesis	0
that	0
SE	3
-	0
induced	0
mossy	0
fiber	0
sprouting	0
and	0
synaptic	0
reorganization	0
are	0
relevant	0
characteristics	0
of	0
seizure	3
development	0
in	0
these	0
murine	0
strains	0
","	0
resembling	0
rat	0
models	0
of	0
human	0
temporal	3
lobe	4
epilepsy	4
.	0
Urinary	3
bladder	4
cancer	4
in	0
Wegener	3
'	4
s	4
granulomatosis	4
:	0
risks	0
and	0
relation	0
to	0
cyclophosphamide	1
.	0
0BJECTIVE	0
:	0
To	0
assess	0
and	0
characterise	0
the	0
risk	0
of	0
bladder	3
cancer	4
","	0
and	0
its	0
relation	0
to	0
cyclophosphamide	1
","	0
in	0
patients	0
with	0
Wegener	3
'	4
s	4
granulomatosis	4
.	0
METH0DS	0
:	0
In	0
the	0
population	0
based	0
","	0
nationwide	0
Swedish	0
Inpatient	0
Register	0
a	0
cohort	0
of	0
1065	0
patients	0
with	0
Wegener	3
'	4
s	4
granulomatosis	4
","	0
1969	0
-	0
95	0
","	0
was	0
identified	0
.	0
Through	0
linkage	0
with	0
the	0
Swedish	0
Cancer	3
Register	0
","	0
all	0
subjects	0
in	0
this	0
cohort	0
diagnosed	0
with	0
bladder	3
cancer	4
were	0
identified	0
.	0
Nested	0
within	0
the	0
cohort	0
","	0
a	0
matched	0
case	0
-	0
control	0
study	0
was	0
performed	0
to	0
estimate	0
the	0
association	0
between	0
cyclophosphamide	1
and	0
bladder	3
cancer	4
using	0
odds	0
ratios	0
(	0
0Rs	0
)	0
as	0
relative	0
risk	0
.	0
In	0
the	0
cohort	0
the	0
cumulative	0
risk	0
of	0
bladder	3
cancer	4
after	0
Wegener	3
'	4
s	4
granulomatosis	4
","	0
and	0
the	0
relative	0
prevalence	0
of	0
a	0
history	0
of	0
bladder	3
cancer	4
at	0
the	0
time	0
of	0
diagnosis	0
of	0
Wegener	3
'	4
s	4
granulomatosis	4
","	0
were	0
also	0
estimated	0
.	0
RESULTS	0
:	0
The	0
median	0
cumulative	0
doses	0
of	0
cyclophosphamide	1
among	0
cases	0
(	0
n	0
=	0
11	0
)	0
and	0
controls	0
(	0
n	0
=	0
25	0
)	0
were	0
113	0
g	0
and	0
25	0
g	0
","	0
respectively	0
.	0
The	0
risk	0
of	0
bladder	3
cancer	4
doubled	0
for	0
every	0
10	0
g	0
increment	0
in	0
cyclophosphamide	1
(	0
0R	0
=	0
2	0
.	0
0	0
","	0
95	0
%	0
confidence	0
interval	0
(	0
CI	0
)	0
0	0
.	0
8	0
to	0
4	0
.	0
9	0
)	0
.	0
Treatment	0
duration	0
longer	0
than	0
1	0
year	0
was	0
associated	0
with	0
an	0
eightfold	0
increased	0
risk	0
(	0
0R	0
=	0
7	0
.	0
7	0
","	0
95	0
%	0
CI	0
0	0
.	0
9	0
to	0
69	0
)	0
.	0
The	0
absolute	0
risk	0
for	0
bladder	3
cancer	4
in	0
the	0
cohort	0
reached	0
10	0
%	0
16	0
years	0
after	0
diagnosis	0
of	0
Wegener	3
'	4
s	4
granulomatosis	4
","	0
and	0
a	0
history	0
of	0
bladder	3
cancer	4
was	0
(	0
non	0
-	0
significantly	0
)	0
twice	0
as	0
common	0
as	0
expected	0
at	0
the	0
time	0
of	0
diagnosis	0
of	0
Wegener	3
'	4
s	4
granulomatosis	4
.	0
C0NCLUSI0N	0
:	0
The	0
results	0
indicate	0
a	0
dose	0
-	0
response	0
relationship	0
between	0
cyclophosphamide	1
and	0
the	0
risk	0
of	0
bladder	3
cancer	4
","	0
high	0
cumulative	0
risks	0
in	0
the	0
entire	0
cohort	0
","	0
and	0
also	0
the	0
possibility	0
of	0
risk	0
factors	0
operating	0
even	0
before	0
Wegener	3
'	4
s	4
granulomatosis	4
.	0
Differential	0
modulation	0
by	0
estrogen	1
of	0
alpha2	0
-	0
adrenergic	0
and	0
I1	0
-	0
imidazoline	1
receptor	0
-	0
mediated	0
hypotension	3
in	0
female	0
rats	0
.	0
We	0
have	0
recently	0
shown	0
that	0
estrogen	1
negatively	0
modulates	0
the	0
hypotensive	3
effect	0
of	0
clonidine	1
(	0
mixed	0
alpha2	0
-	0
/	0
I1	0
-	0
receptor	0
agonist	0
)	0
in	0
female	0
rats	0
and	0
implicates	0
the	0
cardiovascular	0
autonomic	0
control	0
in	0
this	0
interaction	0
.	0
The	0
present	0
study	0
investigated	0
whether	0
this	0
effect	0
of	0
estrogen	1
involves	0
interaction	0
with	0
alpha2	0
-	0
and	0
/	0
or	0
I1	0
-	0
receptors	0
.	0
Changes	0
evoked	0
by	0
a	0
single	0
intraperitoneal	0
injection	0
of	0
rilmenidine	1
(	0
600	0
microg	0
/	0
kg	0
)	0
or	0
alpha	1
-	2
methyldopa	2
(	0
100	0
mg	0
/	0
kg	0
)	0
","	0
selective	0
I1	0
-	0
and	0
alpha2	0
-	0
receptor	0
agonists	0
","	0
respectively	0
","	0
in	0
blood	0
pressure	0
","	0
hemodynamic	0
variability	0
","	0
and	0
locomotor	0
activity	0
were	0
assessed	0
in	0
radiotelemetered	0
sham	0
-	0
operated	0
and	0
ovariectomized	0
(	0
0vx	0
)	0
Sprague	0
-	0
Dawley	0
female	0
rats	0
with	0
or	0
without	0
12	0
-	0
wk	0
estrogen	1
replacement	0
.	0
Three	0
time	0
domain	0
indexes	0
of	0
hemodynamic	0
variability	0
were	0
employed	0
:	0
the	0
standard	0
deviation	0
of	0
mean	0
arterial	0
pressure	0
as	0
a	0
measure	0
of	0
blood	0
pressure	0
variability	0
and	0
the	0
standard	0
deviation	0
of	0
beat	0
-	0
to	0
-	0
beat	0
intervals	0
(	0
SDRR	0
)	0
and	0
the	0
root	0
mean	0
square	0
of	0
successive	0
differences	0
in	0
R	0
-	0
wave	0
-	0
to	0
-	0
R	0
-	0
wave	0
intervals	0
as	0
measures	0
of	0
heart	0
rate	0
variability	0
.	0
In	0
sham	0
-	0
operated	0
rats	0
","	0
rilmenidine	1
or	0
alpha	1
-	2
methyldopa	2
elicited	0
similar	0
hypotension	3
that	0
lasted	0
at	0
least	0
5	0
h	0
and	0
was	0
associated	0
with	0
reductions	0
in	0
standard	0
deviation	0
of	0
mean	0
arterial	0
pressure	0
.	0
SDRR	0
was	0
reduced	0
only	0
by	0
alpha	1
-	2
methyldopa	2
.	0
0vx	0
significantly	0
enhanced	0
the	0
hypotensive	3
response	0
to	0
alpha	1
-	2
methyldopa	2
","	0
in	0
contrast	0
to	0
no	0
effect	0
on	0
rilmenidine	1
hypotension	3
.	0
The	0
enhanced	0
alpha	1
-	2
methyldopa	2
hypotension	3
in	0
0vx	0
rats	0
was	0
paralleled	0
with	0
further	0
reduction	0
in	0
SDRR	0
and	0
a	3
reduced	4
locomotor	4
activity	4
.	0
Estrogen	0
replacement	0
(	0
17beta	1
-	2
estradiol	2
subcutaneous	0
pellet	0
","	0
14	0
.	0
2	0
microg	0
/	0
day	0
","	0
12	0
wk	0
)	0
of	0
0vx	0
rats	0
restored	0
the	0
hemodynamic	0
and	0
locomotor	0
effects	0
of	0
alpha	1
-	2
methyldopa	2
to	0
sham	0
-	0
operated	0
levels	0
.	0
These	0
findings	0
suggest	0
that	0
estrogen	1
downregulates	0
alpha2	0
-	0
but	0
not	0
I1	0
-	0
receptor	0
-	0
mediated	0
hypotension	3
and	0
highlight	0
a	0
role	0
for	0
the	0
cardiac	0
autonomic	0
control	0
in	0
alpha	1
-	2
methyldopa	2
-	0
estrogen	1
interaction	0
.	0
Severe	0
reversible	0
left	3
ventricular	4
systolic	4
and	4
diastolic	4
dysfunction	4
due	0
to	0
accidental	0
iatrogenic	0
epinephrine	1
overdose	3
.	0
Catecholamine	1
-	0
induced	0
cardiomyopathy	3
due	0
to	0
chronic	0
excess	0
of	0
endogenous	0
catecholamines	1
has	0
been	0
recognized	0
for	0
decades	0
as	0
a	0
clinical	0
phenomenon	0
.	0
In	0
contrast	0
","	0
reports	0
of	0
myocardial	3
dysfunction	4
due	0
to	0
acute	0
iatrogenic	0
overdose	3
are	0
rare	0
.	0
A	0
35	0
-	0
year	0
-	0
old	0
woman	0
whose	0
cervix	0
uteri	0
was	0
inadvertently	0
injected	0
with	0
8	0
mg	0
of	0
epinephrine	1
developed	0
myocardial	3
stunning	4
that	0
was	0
characterized	0
by	0
severe	0
hemodynamic	0
compromise	0
","	0
profound	0
","	0
albeit	0
transient	0
","	0
left	3
ventricular	4
systolic	4
and	4
diastolic	4
dysfunction	4
","	0
and	0
only	0
modestly	0
elevated	0
biochemical	0
markers	0
of	0
myocardial	3
necrosis	4
.	0
0ur	0
case	0
illustrates	0
the	0
serious	0
consequences	0
of	0
medical	0
errors	0
that	0
can	0
be	0
avoided	0
through	0
improved	0
medication	0
labeling	0
and	0
staff	0
supervision	0
.	0
Cardioprotective	0
effect	0
of	0
tincture	1
of	2
Crataegus	2
on	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
in	0
rats	0
.	0
Tincture	1
of	2
Crataegus	2
(	0
TCR	1
)	0
","	0
an	0
alcoholic	1
extract	2
of	2
the	2
berries	2
of	2
hawthorn	2
(	0
Crataegus	1
oxycantha	2
)	0
","	0
is	0
used	0
in	0
herbal	0
and	0
homeopathic	0
medicine	0
.	0
The	0
present	0
study	0
was	0
done	0
to	0
investigate	0
the	0
protective	0
effect	0
of	0
TCR	1
on	0
experimentally	0
induced	0
myocardial	3
infarction	4
in	0
rats	0
.	0
Pretreatment	0
of	0
TCR	1
","	0
at	0
a	0
dose	0
of	0
0	0
.	0
5	0
mL	0
/	0
100	0
g	0
bodyweight	0
per	0
day	0
","	0
orally	0
for	0
30	0
days	0
","	0
prevented	0
the	0
increase	0
in	0
lipid	0
peroxidation	0
and	0
activity	0
of	0
marker	0
enzymes	0
observed	0
in	0
isoproterenol	1
-	0
induced	0
rats	0
(	0
85	0
mg	0
kg	0
(	0
-	0
1	0
)	0
s	0
.	0
c	0
.	0
for	0
2	0
days	0
at	0
an	0
interval	0
of	0
24	0
h	0
)	0
.	0
TCR	1
prevented	0
the	0
isoproterenol	1
-	0
induced	0
decrease	0
in	0
antioxidant	0
enzymes	0
in	0
the	0
heart	0
and	0
increased	0
the	0
rate	0
of	0
ADP	1
-	0
stimulated	0
oxygen	1
uptake	0
and	0
respiratory	0
coupling	0
ratio	0
.	0
TCR	1
protected	0
against	0
pathological	0
changes	0
induced	0
by	0
isoproterenol	1
in	0
rat	0
heart	0
.	0
The	0
results	0
show	0
that	0
pretreatment	0
with	0
TCR	1
may	0
be	0
useful	0
in	0
preventing	0
the	0
damage	0
induced	0
by	0
isoproterenol	1
in	0
rat	0
heart	0
.	0
Treatment	0
of	0
tinnitus	3
by	0
intratympanic	0
instillation	0
of	0
lignocaine	1
(	0
lidocaine	1
)	0
2	0
per	0
cent	0
through	0
ventilation	0
tubes	0
.	0
Idiopathic	3
subjective	4
tinnitus	4
(	0
IST	3
)	0
is	0
one	0
of	0
the	0
most	0
obscure	0
otological	0
pathologies	0
.	0
This	0
paper	0
presents	0
the	0
results	0
of	0
treating	0
IST	3
by	0
intratympanic	0
instillation	0
of	0
lignocaine	1
(	0
lidocaine	1
)	0
2	0
per	0
cent	0
through	0
a	0
grommet	0
","	0
for	0
five	0
weekly	0
courses	0
.	0
Fifty	0
-	0
two	0
patients	0
suffering	0
from	0
intractable	0
tinnitus	3
entered	0
this	0
therapeutic	0
trial	0
","	0
but	0
only	0
nine	0
finished	0
all	0
five	0
courses	0
.	0
In	0
one	0
patient	0
","	0
the	0
tinnitus	3
was	0
almost	0
completely	0
abolished	0
","	0
but	0
in	0
all	0
the	0
nine	0
patients	0
the	0
decompensated	0
tinnitus	3
changed	0
to	0
a	0
compensated	0
one	0
.	0
We	0
suggest	0
this	0
mode	0
of	0
treatment	0
for	0
patients	0
that	0
were	0
previously	0
treated	0
by	0
drugs	0
","	0
acupuncture	0
and	0
biofeedback	0
","	0
with	0
disappointing	0
results	0
.	0
Patients	0
should	0
be	0
warned	0
about	0
the	0
side	0
effects	0
of	0
vertigo	3
and	0
vomiting	3
","	0
which	0
subsides	0
gradually	0
with	0
every	0
new	0
instillation	0
","	0
and	0
that	0
the	0
tinnitus	3
may	0
not	0
disappear	0
but	0
will	0
be	0
alleviated	0
","	0
enabling	0
them	0
to	0
cope	0
more	0
easily	0
with	0
the	0
disease	0
and	0
lead	0
a	0
more	0
normal	0
life	0
.	0
The	0
alpha3	0
and	0
beta4	0
nicotinic	0
acetylcholine	1
receptor	0
subunits	0
are	0
necessary	0
for	0
nicotine	1
-	0
induced	0
seizures	3
and	0
hypolocomotion	3
in	0
mice	0
.	0
Binding	0
of	0
nicotine	1
to	0
nicotinic	0
acetylcholine	1
receptors	0
(	0
nAChRs	0
)	0
elicits	0
a	0
series	0
of	0
dose	0
-	0
dependent	0
behaviors	0
that	0
go	0
from	0
altered	0
exploration	0
","	0
sedation	0
","	0
and	0
tremors	3
","	0
to	0
seizures	3
and	0
death	3
.	0
nAChRs	0
are	0
pentameric	0
ion	0
channels	0
usually	0
composed	0
of	0
alpha	0
and	0
beta	0
subunits	0
.	0
A	0
gene	0
cluster	0
comprises	0
the	0
alpha3	0
","	0
alpha5	0
and	0
beta4	0
subunits	0
","	0
which	0
coassemble	0
to	0
form	0
functional	0
receptors	0
.	0
We	0
examined	0
the	0
role	0
of	0
the	0
beta4	0
subunits	0
in	0
nicotine	1
-	0
induced	0
seizures	3
and	0
hypolocomotion	3
in	0
beta4	0
homozygous	0
null	0
(	0
beta4	0
-	0
/	0
-	0
)	0
and	0
alpha3	0
heterozygous	0
(	0
+	0
/	0
-	0
)	0
mice	0
.	0
beta4	0
-	0
/	0
-	0
mice	0
were	0
less	0
sensitive	0
to	0
the	0
effects	0
of	0
nicotine	1
both	0
at	0
low	0
doses	0
","	0
measured	0
as	0
decreased	0
exploration	0
in	0
an	0
open	0
field	0
","	0
and	0
at	0
high	0
doses	0
","	0
measured	0
as	0
sensitivity	0
to	0
nicotine	1
-	0
induced	0
seizures	3
.	0
Using	0
in	0
situ	0
hybridization	0
probes	0
for	0
the	0
alpha3	0
and	0
alpha5	0
subunits	0
","	0
we	0
showed	0
that	0
alpha5	0
mRNA	0
levels	0
are	0
unchanged	0
","	0
whereas	0
alpha3	0
mRNA	0
levels	0
are	0
selectively	0
decreased	0
in	0
the	0
mitral	0
cell	0
layer	0
of	0
the	0
olfactory	0
bulb	0
","	0
and	0
the	0
inferior	0
and	0
the	0
superior	0
colliculus	0
of	0
beta4	0
-	0
/	0
-	0
brains	0
.	0
alpha3	0
+	0
/	0
-	0
mice	0
were	0
partially	0
resistant	0
to	0
nicotine	1
-	0
induced	0
seizures	3
when	0
compared	0
to	0
wild	0
-	0
type	0
littermates	0
.	0
mRNA	0
levels	0
for	0
the	0
alpha5	0
and	0
the	0
beta4	0
subunits	0
were	0
unchanged	0
in	0
alpha3	0
+	0
/	0
-	0
brains	0
.	0
Together	0
","	0
these	0
results	0
suggest	0
that	0
the	0
beta4	0
and	0
the	0
alpha3	0
subunits	0
are	0
mediators	0
of	0
nicotine	1
-	0
induced	0
seizures	3
and	0
hypolocomotion	3
.	0
The	0
effects	0
of	0
sevoflurane	1
on	0
lidocaine	1
-	0
induced	0
convulsions	3
.	0
The	0
influence	0
of	0
sevoflurane	1
on	0
lidocaine	1
-	0
induced	0
convulsions	3
was	0
studied	0
in	0
cats	0
.	0
The	0
convulsive	3
threshold	0
(	0
mean	0
+	0
/	0
-	0
SD	0
)	0
was	0
41	0
.	0
4	0
+	0
/	0
-	0
6	0
.	0
5	0
mg	0
.	0
l	0
(	0
-	0
1	0
)	0
with	0
lidocaine	1
infusion	0
(	0
6	0
mg	0
.	0
kg	0
(	0
-	0
1	0
)	0
.	0
min	0
(	0
-	0
1	0
)	0
)	0
","	0
increasing	0
significantly	0
to	0
66	0
.	0
6	0
+	0
/	0
-	0
10	0
.	0
9	0
mg	0
.	0
l	0
(	0
-	0
1	0
)	0
when	0
the	0
end	0
-	0
tidal	0
concentration	0
of	0
sevoflurane	1
was	0
0	0
.	0
8	0
%	0
.	0
However	0
","	0
the	0
threshold	0
(	0
61	0
.	0
6	0
+	0
/	0
-	0
8	0
.	0
7	0
mg	0
.	0
l	0
(	0
-	0
1	0
)	0
)	0
during	0
1	0
.	0
6	0
%	0
sevoflurane	1
was	0
not	0
significant	0
from	0
that	0
during	0
0	0
.	0
8	0
%	0
sevoflurane	1
","	0
indicating	0
a	0
celling	0
effect	0
.	0
There	0
was	0
no	0
significant	0
difference	0
in	0
the	0
convulsive	3
threshold	0
between	0
sevoflurane	1
and	0
enflurane	1
.	0
The	0
rise	0
in	0
blood	0
pressure	0
became	0
less	0
marked	0
when	0
higher	0
concentrations	0
of	0
sevoflurane	1
or	0
enflurane	1
were	0
administered	0
and	0
the	0
blood	0
pressure	0
at	0
convulsions	3
decreased	0
significantly	0
in	0
1	0
.	0
6	0
%	0
sevoflurane	1
","	0
and	0
in	0
0	0
.	0
8	0
%	0
and	0
1	0
.	0
6	0
%	0
enflurane	1
.	0
However	0
","	0
there	0
was	0
no	0
significant	0
difference	0
in	0
the	0
lidocaine	1
concentrations	0
measured	0
when	0
the	0
systolic	0
blood	0
pressure	0
became	0
70	0
mmHg	0
.	0
Apamin	1
","	0
a	0
selective	0
blocker	0
of	0
calcium	1
-	0
dependent	0
potassium	1
channels	0
","	0
was	0
administered	0
intracerebroventricularly	0
in	0
rats	0
anesthetized	0
with	0
0	0
.	0
8	0
%	0
sevoflurane	1
to	0
investigate	0
the	0
mechanism	0
of	0
the	0
anticonvulsive	0
effects	0
.	0
Apamin	1
(	0
10	0
ng	0
)	0
had	0
a	0
tendency	0
to	0
decrease	0
the	0
convulsive	3
threshold	0
(	0
21	0
.	0
6	0
+	0
/	0
-	0
2	0
.	0
2	0
to	0
19	0
.	0
9	0
+	0
/	0
-	0
2	0
.	0
5	0
mg	0
.	0
l	0
(	0
-	0
1	0
)	0
)	0
but	0
this	0
was	0
not	0
statistically	0
significant	0
.	0
It	0
is	0
suggested	0
that	0
sevoflurane	1
reduces	0
the	0
convulsive	3
effect	0
of	0
lidocaine	1
toxicity	3
but	0
carries	0
some	0
risk	0
due	0
to	0
circulatory	0
depression	3
.	0
Cardiac	3
toxicity	4
observed	0
in	0
association	0
with	0
high	0
-	0
dose	0
cyclophosphamide	1
-	0
based	0
chemotherapy	0
for	0
metastatic	0
breast	3
cancer	4
.	0
INTR0DUCTI0N	0
:	0
Cyclophosphamide	1
is	0
an	0
alkylating	0
agent	0
given	0
frequently	0
as	0
a	0
component	0
of	0
many	0
conditioning	0
regimens	0
.	0
In	0
high	0
doses	0
","	0
its	0
nonhematological	0
dose	0
-	0
limiting	0
toxicity	3
is	0
cardiomyopathy	3
.	0
STUDY	0
DESIGN	0
:	0
We	0
combined	0
paclitaxel	1
","	0
melphalan	1
and	0
high	0
-	0
dose	0
cyclophosphamide	1
","	0
thiotepa	1
","	0
and	0
carboplatin	1
in	0
a	0
triple	0
sequential	0
high	0
-	0
dose	0
regimen	0
for	0
patients	0
with	0
metastatic	0
breast	3
cancer	4
.	0
Analysis	0
was	0
performed	0
on	0
61	0
women	0
with	0
chemotherapy	0
-	0
responsive	0
metastatic	0
breast	3
cancer	4
receiving	0
96	0
-	0
h	0
infusional	0
cyclophosphamide	1
as	0
part	0
of	0
a	0
triple	0
sequential	0
high	0
-	0
dose	0
regimen	0
to	0
assess	0
association	0
between	0
presence	0
of	0
peritransplant	0
congestive	3
heart	4
failure	4
(	0
CHF	3
)	0
and	0
the	0
following	0
pretreatment	0
characteristics	0
:	0
presence	0
of	0
electrocardiogram	0
(	0
EKG	0
)	0
abnormalities	0
","	0
age	0
","	0
hypertension	3
","	0
prior	0
cardiac	0
history	0
","	0
smoking	0
","	0
diabetes	3
mellitus	4
","	0
prior	0
use	0
of	0
anthracyclines	1
","	0
and	0
left	0
-	0
sided	0
chest	0
irradiation	0
.	0
RESULTS	0
:	0
Six	0
of	0
61	0
women	0
(	0
10	0
%	0
)	0
developed	0
clinically	0
reversible	0
grade	0
3	0
CHF	3
following	0
infusional	0
cyclophosphamide	1
with	0
a	0
median	0
percent	0
decline	0
in	0
ejection	0
fraction	0
of	0
31	0
%	0
.	0
Incidence	0
of	0
transient	0
cyclophosphamide	1
-	0
related	0
cardiac	3
toxicity	4
(	0
10	0
%	0
)	0
is	0
comparable	0
to	0
previous	0
recorded	0
literature	0
.	0
0lder	0
age	0
was	0
significantly	0
correlated	0
with	0
the	0
CHF	3
development	0
;	0
with	0
median	0
ages	0
for	0
the	0
entire	0
group	0
and	0
for	0
patients	0
developing	0
CHF	3
of	0
45	0
and	0
59	0
","	0
respectively	0
.	0
No	0
association	0
was	0
found	0
with	0
other	0
pretreatment	0
characteristics	0
.	0
C0NCLUSI0NS	0
:	0
As	0
a	0
result	0
of	0
these	0
findings	0
","	0
oncologists	0
should	0
carefully	0
monitor	0
fluid	0
balance	0
in	0
older	0
patients	0
.	0
Routine	0
EKG	0
monitoring	0
during	0
infusional	0
cyclophosphamide	1
did	0
not	0
predict	0
CHF	3
development	0
.	0
Tremor	3
side	0
effects	0
of	0
salbutamol	1
","	0
quantified	0
by	0
a	0
laser	0
pointer	0
technique	0
.	0
0BJECTIVE	0
:	0
To	0
study	0
tremor	3
side	0
effects	0
of	0
salbutamol	1
an	0
easily	0
applicable	0
","	0
quick	0
and	0
low	0
-	0
priced	0
method	0
is	0
needed	0
.	0
A	0
new	0
method	0
using	0
a	0
commercially	0
available	0
","	0
pen	0
-	0
shaped	0
laser	0
pointer	0
was	0
developed	0
.	0
Aim	0
of	0
the	0
study	0
was	0
to	0
determine	0
sensitivity	0
","	0
reproducibility	0
","	0
reference	0
values	0
and	0
the	0
agreement	0
with	0
a	0
questionnaire	0
.	0
METH0DS	0
:	0
Tremor	3
was	0
measured	0
using	0
a	0
laser	0
pointer	0
technique	0
.	0
To	0
determine	0
sensitivity	0
we	0
assessed	0
tremor	3
in	0
44	0
patients	0
with	0
obstructive	3
lung	4
disease	4
after	0
administration	0
of	0
cumulative	0
doses	0
of	0
salbutamol	1
.	0
Subjects	0
were	0
asked	0
to	0
aim	0
at	0
the	0
centre	0
of	0
a	0
target	0
","	0
subdivided	0
in	0
concentric	0
circles	0
","	0
from	0
5	0
m	0
distance	0
.	0
The	0
circle	0
in	0
which	0
the	0
participant	0
succeeded	0
to	0
aim	0
was	0
recorded	0
in	0
millimetres	0
radius	0
.	0
In	0
another	0
series	0
of	0
measurements	0
","	0
reproducibility	0
and	0
reference	0
values	0
of	0
the	0
tremor	3
was	0
assessed	0
in	0
65	0
healthy	0
subjects	0
in	0
three	0
sessions	0
","	0
at	0
9	0
a	0
.	0
m	0
.	0
","	0
4	0
p	0
.	0
m	0
.	0
and	0
9	0
a	0
.	0
m	0
.	0
","	0
respectively	0
","	0
1	0
week	0
later	0
.	0
Postural	0
tremor	3
was	0
measured	0
with	0
the	0
arm	0
horizontally	0
outstretched	0
rest	0
tremor	3
with	0
the	0
arm	0
supported	0
by	0
an	0
armrest	0
and	0
finally	0
tremor	3
was	0
measured	0
after	0
holding	0
a	0
2	0
-	0
kg	0
weight	0
until	0
exhaustion	0
.	0
Inter	0
-	0
observer	0
variability	0
was	0
measured	0
in	0
a	0
series	0
of	0
10	0
healthy	0
subjects	0
.	0
Tremor	3
was	0
measured	0
simultaneously	0
by	0
two	0
independent	0
observers	0
.	0
RESULTS	0
:	0
Salbutamol	1
significantly	0
increased	0
tremor	3
severity	0
in	0
patients	0
in	0
a	0
dose	0
-	0
dependent	0
way	0
.	0
Within	0
healthy	0
adults	0
no	0
age	0
-	0
dependency	0
could	0
be	0
found	0
(	0
b	0
=	0
0	0
.	0
262	0
mm	0
/	0
year	0
;	0
P	0
=	0
0	0
.	0
72	0
)	0
.	0
There	0
was	0
no	0
agreement	0
between	0
the	0
questionnaire	0
and	0
tremor	3
severity	0
(	0
r	0
=	0
0	0
.	0
93	0
;	0
P	0
=	0
0	0
.	0
53	0
)	0
.	0
Postural	0
tremor	3
showed	0
no	0
significant	0
difference	0
between	0
the	0
first	0
and	0
third	0
session	0
(	0
P	0
=	0
0	0
.	0
7	0
)	0
.	0
Support	0
of	0
the	0
arm	0
decreased	0
tremor	3
severity	0
","	0
exhaustion	0
increased	0
tremor	3
severity	0
significantly	0
.	0
A	0
good	0
agreement	0
was	0
found	0
between	0
two	0
independent	0
observers	0
(	0
interclass	0
correlation	0
coefficient	0
0	0
.	0
72	0
)	0
.	0
DISCUSSI0N	0
:	0
Quantifying	0
tremor	3
by	0
using	0
an	0
inexpensive	0
laser	0
pointer	0
is	0
","	0
with	0
the	0
exception	0
of	0
children	0
(	0
<	0
12	0
years	0
)	0
a	0
sensitive	0
and	0
reproducible	0
method	0
.	0
Safety	0
and	0
adverse	0
effects	0
associated	0
with	0
raloxifene	1
:	0
multiple	0
outcomes	0
of	0
raloxifene	1
evaluation	0
.	0
0BJECTIVE	0
:	0
To	0
examine	0
the	0
effect	0
of	0
raloxifene	1
on	0
major	0
adverse	0
events	0
that	0
occur	0
with	0
postmenopausal	0
estrogen	1
therapy	0
or	0
tamoxifen	1
.	0
METH0DS	0
:	0
The	0
Multiple	0
0utcomes	0
of	0
Raloxifene	1
Evaluation	0
","	0
a	0
multicenter	0
","	0
randomized	0
","	0
double	0
-	0
blind	0
trial	0
","	0
enrolled	0
7	0
","	0
705	0
postmenopausal	0
women	0
with	0
osteoporosis	3
.	0
Women	0
were	0
randomly	0
assigned	0
to	0
raloxifene	1
60	0
mg	0
/	0
d	0
or	0
120	0
mg	0
/	0
d	0
or	0
placebo	0
.	0
0utcomes	0
included	0
venous	3
thromboembolism	4
","	0
cataracts	3
","	0
gallbladder	3
disease	4
","	0
and	0
endometrial	3
hyperplasia	4
or	4
cancer	4
.	0
RESULTS	0
:	0
During	0
a	0
mean	0
follow	0
-	0
up	0
of	0
3	0
.	0
3	0
years	0
","	0
raloxifene	1
was	0
associated	0
with	0
an	0
increased	0
risk	0
for	0
venous	3
thromboembolism	4
(	0
relative	0
risk	0
[	0
RR	0
]	0
2	0
.	0
1	0
;	0
95	0
%	0
confidence	0
interval	0
[	0
CI	0
]	0
1	0
.	0
2	0
-	0
3	0
.	0
8	0
)	0
.	0
The	0
excess	0
event	0
rate	0
was	0
1	0
.	0
8	0
per	0
1	0
","	0
0	0
woman	0
-	0
years	0
(	0
95	0
%	0
CI	0
-	0
0	0
.	0
5	0
-	0
4	0
.	0
1	0
)	0
","	0
and	0
the	0
number	0
needed	0
to	0
treat	0
to	0
cause	0
1	0
event	0
was	0
170	0
(	0
95	0
%	0
CI	0
100	0
-	0
582	0
)	0
over	0
3	0
.	0
3	0
years	0
.	0
Risk	0
in	0
the	0
raloxifene	1
group	0
was	0
higher	0
than	0
in	0
the	0
placebo	0
group	0
for	0
the	0
first	0
2	0
years	0
","	0
but	0
decreased	0
to	0
about	0
the	0
same	0
rate	0
as	0
in	0
the	0
placebo	0
group	0
thereafter	0
.	0
Raloxifene	1
did	0
not	0
increase	0
risk	0
for	0
cataracts	3
(	0
RR	0
0	0
.	0
9	0
;	0
95	0
%	0
CI	0
0	0
.	0
8	0
-	0
1	0
.	0
1	0
)	0
","	0
gallbladder	3
disease	4
(	0
RR	0
1	0
.	0
0	0
;	0
95	0
%	0
CI	0
0	0
.	0
7	0
-	0
1	0
.	0
3	0
)	0
","	0
endometrial	3
hyperplasia	4
(	0
RR	0
1	0
.	0
3	0
;	0
95	0
%	0
CI	0
0	0
.	0
4	0
-	0
5	0
.	0
1	0
)	0
","	0
or	0
endometrial	3
cancer	4
(	0
RR	0
0	0
.	0
9	0
;	0
95	0
%	0
CI	0
0	0
.	0
3	0
-	0
2	0
.	0
7	0
)	0
.	0
C0NCLUSI0N	0
:	0
Raloxifene	1
was	0
associated	0
with	0
an	0
increased	0
risk	0
for	0
venous	3
thromboembolism	4
","	0
but	0
there	0
was	0
no	0
increased	0
risk	0
for	0
cataracts	3
","	0
gallbladder	3
disease	4
","	0
endometrial	3
hyperplasia	4
","	0
or	0
endometrial	3
cancer	4
.	0
LEVEL	0
0F	0
EVIDENCE	0
:	0
I	0
0ptimization	0
of	0
levodopa	1
therapy	0
.	0
While	0
there	0
is	0
no	0
single	0
correct	0
starting	0
dose	0
for	0
levodopa	1
therapy	0
","	0
many	0
individuals	0
can	0
be	0
started	0
on	0
either	0
the	0
25	0
/	0
100	0
or	0
controlled	0
-	0
release	0
formula	0
","	0
following	0
the	0
general	0
rule	0
not	0
to	0
attempt	0
to	0
titrate	0
carbidopa	1
-	0
levodopa	1
to	0
the	0
point	0
of	0
"	0
normality	0
,	0
"	0
which	0
can	0
lead	0
to	0
toxicity	3
.	0
The	0
physician	0
should	0
also	0
determine	0
the	0
proper	0
use	0
of	0
any	0
adjunctive	0
medications	0
;	0
such	0
combined	0
therapy	0
has	0
become	0
the	0
standard	0
approach	0
to	0
treatment	0
.	0
Following	0
the	0
initial	0
period	0
of	0
therapy	0
","	0
emerging	0
difficulties	0
require	0
a	0
reassessment	0
of	0
therapeutic	0
approaches	0
","	0
such	0
as	0
dosage	0
adjustment	0
or	0
introduction	0
of	0
a	0
dopamine	1
agonist	0
.	0
0ther	0
possible	0
adverse	0
effects	0
-	0
-	0
such	0
as	0
gastrointestinal	3
disorders	4
","	0
orthostatic	3
hypotension	4
","	0
levodopa	1
-	0
induced	0
psychosis	3
","	0
sleep	3
disturbances	4
or	0
parasomnias	3
","	0
or	0
drug	0
interactions	0
-	0
-	0
also	0
require	0
carefully	0
monitored	0
individual	0
treatment	0
.	0
Nonpharmacologic	0
concerns	0
can	0
help	0
the	0
Parkinson	3
'	4
s	4
disease	4
patient	0
achieve	0
and	0
maintain	0
optimal	0
functioning	0
","	0
including	0
daily	0
exercise	0
","	0
physical	0
therapy	0
","	0
and	0
involvement	0
with	0
support	0
groups	0
.	0
Long	0
term	0
audiological	0
evaluation	0
of	0
beta	3
-	4
thalassemic	4
patients	0
.	0
0BJECTIVE	0
:	0
The	0
objective	0
of	0
this	0
study	0
was	0
to	0
identify	0
the	0
incidence	0
and	0
to	0
monitor	0
the	0
progression	0
of	0
hearing	3
loss	4
in	0
children	0
and	0
young	0
adults	0
with	0
beta	3
-	4
thalassemia	4
major	0
.	0
METH0DS	0
:	0
0ne	0
hundred	0
and	0
four	0
(	0
104	0
)	0
patients	0
aged	0
6	0
-	0
35	0
years	0
(	0
mean	0
17	0
","	0
2	0
years	0
)	0
participated	0
in	0
the	0
study	0
.	0
All	0
patients	0
were	0
on	0
a	0
regular	0
transfusion	0
-	0
chelation	0
program	0
maintaining	0
a	0
mean	0
hemoglobin	0
level	0
of	0
9	0
.	0
5	0
gr	0
/	0
dl	0
.	0
Subjects	0
were	0
receiving	0
desferrioxamine	1
(	0
DF0	1
)	0
chelation	0
treatment	0
with	0
a	0
mean	0
daily	0
dose	0
of	0
50	0
-	0
60	0
mg	0
/	0
kg	0
","	0
5	0
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50	0
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-	0
14	0
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","	0
21	0
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104	0
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2	0
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SNHL	3
)	0
","	0
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No	0
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","	0
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DF0	1
","	0
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","	0
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","	0
7	0
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21	0
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","	0
10	0
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4	0
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C0NCLUSI0N	0
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The	0
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adriamycin	1
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.	0
BACKGR0UND	0
:	0
In	0
man	0
","	0
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angiotensin	1
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ACE	0
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","	0
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I	0
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","	0
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renal	0
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","	0
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the	0
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the	0
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renal	3
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a	0
single	0
injection	0
of	0
adriamycin	1
in	0
rats	0
.	0
METH0DS	0
:	0
Renal	0
ACE	0
activity	0
(	0
Hip	1
-	2
His	2
-	2
Leu	2
cleavage	0
by	0
cortical	0
homogenates	0
)	0
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determined	0
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renal	0
biopsy	0
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27	0
adult	0
male	0
Wistar	0
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.	0
After	0
1	0
week	0
of	0
recovery	0
","	0
proteinuria	3
was	0
induced	0
by	0
adriamycin	1
[	0
1	0
.	0
5	0
mg	0
/	0
kg	0
intravenously	0
(	0
i	0
.	0
v	0
.	0
)	0
n	0
=	0
18	0
;	0
controls	0
","	0
saline	0
i	0
.	0
v	0
.	0
n	0
=	0
9	0
]	0
.	0
Proteinuria	3
was	0
measured	0
every	0
2	0
weeks	0
.	0
After	0
12	0
weeks	0
","	0
rats	0
were	0
sacrificed	0
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their	0
kidneys	0
harvested	0
.	0
RESULTS	0
:	0
As	0
anticipated	0
","	0
adriamycin	1
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nephrotic	3
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proteinuria	3
","	0
renal	3
interstitial	4
damage	4
and	0
mild	0
focal	3
glomerulosclerosis	4
.	0
Baseline	0
renal	0
ACE	0
positively	0
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with	0
the	0
relative	0
rise	0
in	0
proteinuria	3
after	0
adriamycin	1
(	0
r	0
=	0
0	0
.	0
62	0
","	0
P	0
<	0
0	0
.	0
1	0
)	0
","	0
renal	0
interstitial	0
alpha	0
-	0
smooth	0
muscle	0
actin	0
(	0
r	0
=	0
0	0
.	0
49	0
","	0
P	0
<	0
0	0
.	0
5	0
)	0
","	0
interstitial	0
macrophage	0
influx	0
(	0
r	0
=	0
0	0
.	0
56	0
","	0
P	0
<	0
0	0
.	0
5	0
)	0
","	0
interstitial	0
collagen	0
III	0
(	0
r	0
=	0
0	0
.	0
53	0
","	0
P	0
<	0
0	0
.	0
5	0
)	0
","	0
glomerular	0
alpha	0
-	0
smooth	0
muscle	0
actin	0
(	0
r	0
=	0
0	0
.	0
74	0
","	0
P	0
<	0
0	0
.	0
1	0
)	0
and	0
glomerular	0
desmin	0
(	0
r	0
=	0
0	0
.	0
48	0
","	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
Baseline	0
renal	0
ACE	0
did	0
not	0
correlate	0
with	0
focal	3
glomerulosclerosis	4
(	0
r	0
=	0
0	0
.	0
22	0
","	0
NS	0
)	0
.	0
In	0
controls	0
","	0
no	0
predictive	0
values	0
for	0
renal	0
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observed	0
.	0
C0NCLUSI0N	0
:	0
Individual	0
differences	0
in	0
renal	0
ACE	0
activity	0
predict	0
the	0
severity	0
of	0
adriamycin	1
-	0
induced	0
renal	3
damage	4
in	0
this	0
outbred	0
rat	0
strain	0
.	0
This	0
supports	0
the	0
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that	0
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in	0
renal	0
ACE	0
activity	0
predispose	0
to	0
a	0
less	0
favourable	0
course	0
of	0
renal	3
damage	4
.	0
Recurrent	0
acute	0
interstitial	3
nephritis	4
induced	0
by	0
azithromycin	1
.	0
A	0
14	0
-	0
year	0
-	0
old	0
girl	0
is	0
reported	0
with	0
recurrent	0
","	0
azithromycin	1
-	0
induced	0
","	0
acute	0
interstitial	3
nephritis	4
.	0
The	0
second	0
episode	0
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severe	0
than	0
the	0
first	0
;	0
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although	0
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intensive	0
corticosteroid	0
therapy	0
","	0
renal	0
function	0
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.	0
Although	0
most	0
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of	0
antibiotic	0
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acute	0
interstitial	3
nephritis	4
are	0
benign	0
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self	0
-	0
limited	0
","	0
some	0
patients	0
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at	0
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permanent	0
renal	3
injury	4
.	0
Spironolactone	1
-	0
induced	0
renal	3
insufficiency	4
and	0
hyperkalemia	3
in	0
patients	0
with	0
heart	3
failure	4
.	0
BACKGR0UND	0
:	0
A	0
previous	0
randomized	0
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trial	0
evaluating	0
the	0
use	0
of	0
spironolactone	1
in	0
heart	3
failure	4
patients	0
reported	0
a	0
low	0
risk	0
of	0
hyperkalemia	3
(	0
2	0
%	0
)	0
and	0
renal	3
insufficiency	4
(	0
0	0
%	0
)	0
.	0
Because	0
treatments	0
for	0
heart	3
failure	4
have	0
changed	0
since	0
the	0
benefits	0
of	0
spironolactone	1
were	0
reported	0
","	0
the	0
prevalence	0
of	0
these	0
complications	0
may	0
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in	0
current	0
clinical	0
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.	0
We	0
therefore	0
sought	0
to	0
determine	0
the	0
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clinical	0
associations	0
of	0
hyperkalemia	3
and	0
renal	3
insufficiency	4
in	0
heart	3
failure	4
patients	0
treated	0
with	0
spironolactone	1
.	0
METH0DS	0
:	0
We	0
performed	0
a	0
case	0
control	0
study	0
of	0
heart	3
failure	4
patients	0
treated	0
with	0
spironolactone	1
in	0
our	0
clinical	0
practice	0
.	0
Cases	0
were	0
patients	0
who	0
developed	0
hyperkalemia	3
(	0
K	1
(	0
+	0
)	0
>	0
5	0
.	0
0	0
mEq	0
/	0
L	0
)	0
or	0
renal	3
insufficiency	4
(	0
Cr	1
>	0
or	0
=	0
2	0
.	0
5	0
mg	0
/	0
dL	0
)	0
","	0
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2	0
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per	0
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.	0
Clinical	0
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","	0
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","	0
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at	0
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-	0
up	0
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.	0
RESULTS	0
:	0
Sixty	0
-	0
seven	0
of	0
926	0
patients	0
(	0
7	0
.	0
2	0
%	0
)	0
required	0
discontinuation	0
of	0
spironolactone	1
due	0
to	0
hyperkalemia	3
(	0
n	0
=	0
33	0
)	0
or	0
renal	3
failure	4
(	0
n	0
=	0
34	0
)	0
.	0
Patients	0
who	0
developed	0
hyperkalemia	3
were	0
older	0
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likely	0
to	0
have	0
diabetes	3
","	0
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potassium	1
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potassium	1
supplement	0
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","	0
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beta	0
-	0
blockers	0
than	0
controls	0
(	0
n	0
=	0
134	0
)	0
.	0
Patients	0
who	0
developed	0
renal	3
insufficiency	4
had	0
lower	0
baseline	0
body	0
weight	0
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baseline	0
serum	0
creatinine	1
","	0
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loop	0
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","	0
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likely	0
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thiazide	1
diuretics	0
than	0
controls	0
.	0
C0NCLUSI0NS	0
:	0
Spironolactone	1
-	0
induced	0
hyperkalemia	3
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renal	3
insufficiency	4
are	0
more	0
common	0
in	0
our	0
clinical	0
experience	0
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reported	0
previously	0
.	0
This	0
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is	0
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by	0
patient	0
comorbidities	0
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more	0
frequent	0
use	0
of	0
beta	0
-	0
blockers	0
.	0
Acute	0
reserpine	1
and	0
subchronic	0
haloperidol	1
treatments	0
change	0
synaptosomal	0
brain	0
glutamate	1
uptake	0
and	0
elicit	0
orofacial	3
dyskinesia	4
in	0
rats	0
.	0
Reserpine	1
-	0
and	0
haloperidol	1
-	0
induced	0
orofacial	3
dyskinesia	4
are	0
putative	0
animal	0
models	0
of	0
tardive	3
dyskinesia	4
(	0
TD	3
)	0
whose	0
pathophysiology	0
has	0
been	0
related	0
to	0
free	0
radical	0
generation	0
and	0
oxidative	0
stress	0
.	0
In	0
the	0
present	0
study	0
","	0
the	0
authors	0
induced	0
orofacial	3
dyskinesia	4
by	0
acute	0
reserpine	1
and	0
subchronic	0
haloperidol	1
administration	0
to	0
rats	0
.	0
Reserpine	1
injection	0
(	0
one	0
dose	0
of	0
1	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
every	0
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3	0
days	0
caused	0
a	0
significant	0
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in	0
vacuous	0
chewing	0
","	0
tongue	0
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of	0
facial	0
twitching	0
","	0
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the	0
control	0
.	0
Haloperidol	1
administration	0
(	0
one	0
dose	0
of	0
12	0
mg	0
/	0
kg	0
once	0
a	0
week	0
s	0
.	0
c	0
.	0
)	0
for	0
4	0
weeks	0
caused	0
an	0
increase	0
in	0
vacuous	0
chewing	0
","	0
tongue	0
protrusion	0
and	0
duration	0
of	0
facial	0
twitching	0
observed	0
in	0
four	0
weekly	0
evaluations	0
.	0
After	0
the	0
treatments	0
and	0
behavioral	0
observation	0
","	0
glutamate	1
uptake	0
by	0
segments	0
of	0
the	0
brain	0
was	0
analyzed	0
.	0
A	0
decreased	0
glutamate	1
uptake	0
was	0
observed	0
in	0
the	0
subcortical	0
parts	0
of	0
animals	0
treated	0
with	0
reserpine	1
and	0
haloperidol	1
","	0
compared	0
to	0
the	0
control	0
.	0
Importantly	0
","	0
a	0
decrease	0
in	0
glutamate	1
uptake	0
correlates	0
negatively	0
with	0
an	0
increase	0
in	0
the	0
incidence	0
of	0
orofacial	3
diskinesia	4
.	0
These	0
results	0
indicate	0
that	0
early	0
changes	0
in	0
glutamate	1
transport	0
may	0
be	0
related	0
to	0
the	0
development	0
of	0
vacuous	0
chewing	0
movements	0
in	0
rats	0
.	0
Ceftriaxone	1
-	0
associated	0
biliary	3
pseudolithiasis	4
in	0
paediatric	0
surgical	0
patients	0
.	0
It	0
is	0
well	0
known	0
that	0
ceftriaxone	1
leads	0
to	0
pseudolithiasis	3
in	0
some	0
patients	0
.	0
Clinical	0
and	0
experimental	0
studies	0
also	0
suggest	0
that	0
situations	0
causing	0
gallbladder	3
dysfunction	4
","	0
such	0
as	0
fasting	0
","	0
may	0
have	0
a	0
role	0
for	0
the	0
development	0
of	0
pseudolithiasis	3
.	0
In	0
this	0
study	0
","	0
we	0
prospectively	0
evaluated	0
the	0
incidence	0
and	0
clinical	0
importance	0
of	0
pseudolithiasis	3
in	0
paediatric	0
surgical	0
patients	0
receiving	0
ceftriaxone	1
treatment	0
","	0
who	0
often	0
had	0
to	0
fast	0
in	0
the	0
post	0
-	0
operative	0
period	0
.	0
Fifty	0
children	0
who	0
were	0
given	0
ceftriaxone	1
were	0
evaluated	0
by	0
serial	0
abdominal	0
sonograms	0
.	0
0f	0
those	0
","	0
13	0
(	0
26	0
%	0
)	0
developed	0
biliary	0
pathology	0
.	0
Comparison	0
of	0
the	0
patients	0
with	0
or	0
without	0
pseudolithiasis	3
revealed	0
no	0
significant	0
difference	0
with	0
respect	0
to	0
age	0
","	0
sex	0
","	0
duration	0
of	0
the	0
treatment	0
and	0
starvation	0
variables	0
.	0
After	0
cessation	0
of	0
the	0
treatment	0
","	0
pseudolithiasis	3
resolved	0
spontaneously	0
within	0
a	0
short	0
period	0
.	0
The	0
incidence	0
of	0
pseudolithiasis	3
is	0
not	0
affected	0
by	0
fasting	0
.	0
Coronary	3
aneurysm	4
after	0
implantation	0
of	0
a	0
paclitaxel	1
-	0
eluting	0
stent	0
.	0
Formation	0
of	0
coronary	3
aneurysm	4
is	0
a	0
rare	0
complication	0
of	0
stenting	0
with	0
bare	0
metal	0
stents	0
","	0
but	0
based	0
on	0
experimental	0
studies	0
drug	0
-	0
eluting	0
stents	0
may	0
induce	0
toxic	0
effects	0
on	0
the	0
vessel	0
wall	0
with	0
incomplete	0
stent	0
apposition	0
","	0
aneurysm	3
formation	0
and	0
with	0
the	0
potential	0
of	0
stent	0
thrombosis	3
or	0
vessel	3
rupture	4
.	0
We	0
present	0
a	0
43	0
-	0
year	0
-	0
old	0
man	0
who	0
developed	0
a	0
coronary	3
aneurysm	4
in	0
the	0
right	0
coronary	0
artery	0
6	0
months	0
after	0
receiving	0
a	0
paclitaxel	1
-	0
eluting	0
stent	0
.	0
The	0
patient	0
was	0
asymptomatic	0
and	0
the	0
aneurysm	3
was	0
detected	0
in	0
a	0
routine	0
control	0
.	0
Angiography	0
and	0
intracoronary	0
ultrasound	0
demonstrated	0
lack	0
of	0
contact	0
between	0
stent	0
and	0
vessel	0
wall	0
in	0
a	0
15	0
-	0
mm	0
long	0
segment	0
with	0
maximal	0
aneurysm	3
diameter	0
of	0
6	0
.	0
0	0
mm	0
.	0
The	0
patient	0
was	0
successfully	0
treated	0
with	0
a	0
graft	0
stent	0
.	0
Causes	0
of	0
acute	0
thrombotic	3
microangiopathy	4
in	0
patients	0
receiving	0
kidney	0
transplantation	0
.	0
0BJECTIVES	0
:	0
Thrombotic	3
microangiopathy	4
is	0
a	0
well	0
-	0
known	0
problem	0
in	0
patients	0
following	0
renal	0
transplantation	0
.	0
In	0
postrenal	0
transplantation	0
","	0
thrombotic	3
microangiopathy	4
is	0
often	0
a	0
reflection	0
of	0
hemolytic	3
uremic	4
syndrome	4
.	0
We	0
aimed	0
to	0
determine	0
the	0
causes	0
of	0
thrombotic	3
microangiopathy	4
in	0
a	0
population	0
of	0
renal	0
transplantation	0
recipients	0
and	0
discuss	0
the	0
literature	0
.	0
MATERIALS	0
AND	0
METH0DS	0
:	0
We	0
investigated	0
the	0
causes	0
of	0
thrombotic	3
microangiopathy	4
during	0
a	0
1	0
-	0
year	0
period	0
","	0
from	0
June	0
2003	0
to	0
June	0
2004	0
","	0
at	0
the	0
King	0
Fahad	0
National	0
Guard	0
Hospital	0
in	0
Riyadh	0
","	0
Saudi	0
Arabia	0
","	0
by	0
reviewing	0
the	0
slides	0
of	0
all	0
transplant	0
biopsies	0
(	0
n	0
=	0
25	0
)	0
performed	0
during	0
this	0
interval	0
.	0
Pre	0
-	0
and	0
posttransplant	0
crossmatching	0
was	0
done	0
when	0
possible	0
.	0
RESULTS	0
:	0
Five	0
cases	0
of	0
thrombotic	3
microangiopathy	4
were	0
found	0
.	0
Three	0
of	0
these	0
cases	0
were	0
from	0
the	0
25	0
transplantations	0
performed	0
at	0
King	0
Fahad	0
National	0
Guard	0
Hospital	0
","	0
while	0
the	0
other	0
2	0
transplantations	0
had	0
been	0
performed	0
abroad	0
and	0
were	0
referred	0
to	0
us	0
for	0
follow	0
-	0
up	0
.	0
Three	0
cases	0
were	0
related	0
to	0
cyclosporine	1
","	0
and	0
1	0
case	0
was	0
secondary	0
to	0
both	0
cyclosporine	1
and	0
tacrolimus	1
.	0
The	0
fifth	0
case	0
had	0
features	0
of	0
thrombotic	3
microangiopathy	4
related	0
to	0
an	0
antiphospholipid	3
syndrome	4
in	0
a	0
patient	0
with	0
systemic	3
lupus	4
erythematosus	4
.	0
C0NCLUSI0NS	0
:	0
In	0
the	0
literature	0
","	0
the	0
most	0
-	0
frequent	0
cause	0
of	0
hemolytic	3
uremic	4
syndrome	4
in	0
patients	0
following	0
renal	0
transplantation	0
is	0
recurrence	0
of	0
the	0
hemolytic	3
uremic	4
syndrome	4
.	0
0ther	0
causes	0
include	0
drug	0
-	0
related	0
(	0
cyclosporine	1
","	0
tacrolimus	1
)	0
toxicity	3
","	0
procoagulant	0
status	0
","	0
and	0
antibody	0
-	0
mediated	0
rejection	0
.	0
We	0
found	0
that	0
the	0
most	0
-	0
frequent	0
cause	0
of	0
thrombotic	3
microangiopathy	4
was	0
drug	0
related	0
","	0
secondary	0
mainly	0
to	0
cyclosporine	1
.	0
In	0
the	0
current	0
study	0
","	0
the	0
frequency	0
of	0
thrombotic	3
microangiopathy	4
was	0
similar	0
to	0
the	0
percentage	0
reported	0
in	0
the	0
literature	0
(	0
20	0
%	0
)	0
.	0
Comparison	0
of	0
developmental	0
toxicity	3
of	0
selective	0
and	0
non	0
-	0
selective	0
cyclooxygenase	0
-	0
2	0
inhibitors	0
in	0
CRL	0
:	0
(	0
WI	0
)	0
WUBR	0
Wistar	0
rats	0
-	0
-	0
DFU	1
and	0
piroxicam	1
study	0
.	0
BACKGR0UND	0
:	0
Cyclooxygenase	0
(	0
C0X	0
)	0
inhibitors	0
are	0
one	0
of	0
the	0
most	0
often	0
ingested	0
drugs	0
during	0
pregnancy	0
.	0
Unlike	0
general	0
toxicity	3
data	0
","	0
their	0
prenatal	0
toxic	0
effects	0
were	0
not	0
extensively	0
studied	0
before	0
.	0
The	0
aim	0
of	0
the	0
experiment	0
was	0
to	0
evaluate	0
the	0
developmental	0
toxicity	3
of	0
the	0
non	0
-	0
selective	0
(	0
piroxicam	1
)	0
and	0
selective	0
(	0
DFU	1
;	0
5	1
","	2
5	2
-	2
dimethyl	2
-	2
3	2
-	2
(	2
3	2
-	2
fluorophenyl	2
)	2
-	2
4	2
-	2
(	2
4	2
-	2
methylsulphonyl	2
)	2
phenyl	2
-	2
2	2
(	2
5H	2
)	2
-	2
furanon	2
)	0
C0X	0
-	0
2	0
inhibitors	0
.	0
METH0DS	0
:	0
Drugs	0
were	0
separately	0
","	0
orally	0
once	0
daily	0
dosed	0
to	0
pregnant	0
rats	0
from	0
day	0
8	0
to	0
21	0
(	0
GD1	0
=	0
plug	0
day	0
)	0
.	0
Doses	0
were	0
set	0
at	0
0	0
.	0
3	0
","	0
3	0
.	0
0	0
and	0
30	0
.	0
0mg	0
/	0
kg	0
for	0
piroxicam	1
and	0
0	0
.	0
2	0
","	0
2	0
.	0
0	0
and	0
20	0
.	0
0mg	0
/	0
kg	0
for	0
DFU	1
.	0
Fetuses	0
were	0
delivered	0
on	0
GD	0
21	0
and	0
routinely	0
examined	0
.	0
Comprehensive	0
clinical	0
and	0
developmental	0
measurements	0
were	0
done	0
.	0
The	0
pooled	0
statistical	0
analysis	0
for	0
ventricular	3
septal	4
(	4
VSD	4
)	4
and	4
midline	4
(	4
MD	4
)	4
defects	4
was	0
performed	0
for	0
rat	0
fetuses	0
exposed	0
to	0
piroxicam	1
","	0
selective	0
and	0
non	0
-	0
selective	0
C0X	0
-	0
2	0
inhibitor	0
based	0
on	0
present	0
and	0
historic	0
data	0
.	0
RESULTS	0
:	0
Maternal	0
toxicity	3
","	0
intrauterine	3
growth	4
retardation	4
","	0
and	0
increase	3
of	4
external	4
and	4
skeletal	4
variations	4
were	0
found	0
in	0
rats	0
treated	0
with	0
the	0
highest	0
dose	0
of	0
piroxicam	1
.	0
Decrease	0
of	0
fetal	0
length	0
was	0
the	0
only	0
signs	0
of	0
the	0
DFU	1
developmental	0
toxicity	3
observed	0
in	0
pups	0
exposed	0
to	0
the	0
highest	0
compound	0
dose	0
.	0
Lack	0
of	0
teratogenicity	0
was	0
found	0
in	0
piroxicam	1
and	0
DFU	1
-	0
exposed	0
groups	0
.	0
Prenatal	0
exposure	0
to	0
non	0
-	0
selective	0
C0X	0
inhibitors	0
increases	0
the	0
risk	0
of	0
VSD	0
and	0
MD	0
when	0
compared	0
to	0
historic	0
control	0
but	0
not	0
with	0
selective	0
C0X	0
-	0
2	0
inhibitors	0
.	0
C0NCLUSI0N	0
:	0
Both	0
selective	0
and	0
non	0
-	0
selective	0
C0X	0
-	0
2	0
inhibitors	0
were	0
toxic	0
for	0
rats	0
fetuses	0
when	0
administered	0
in	0
the	0
highest	0
dose	0
.	0
Unlike	0
DFU	1
","	0
piroxicam	1
was	0
also	0
highly	0
toxic	0
to	0
the	0
dams	0
.	0
Prenatal	0
exposure	0
to	0
selective	0
C0X	0
-	0
2	0
inhibitors	0
does	0
not	0
increase	0
the	0
risk	0
of	0
ventricular	3
septal	4
and	4
midline	4
defects	4
in	0
rat	0
when	0
compared	0
to	0
non	0
-	0
selective	0
drugs	0
and	0
historic	0
control	0
.	0
Lone	0
atrial	3
fibrillation	4
associated	0
with	0
creatine	1
monohydrate	0
supplementation	0
.	0
Atrial	3
fibrillation	4
in	0
young	0
patients	0
without	0
structural	0
heart	3
disease	4
is	0
rare	0
.	0
Therefore	0
","	0
when	0
the	0
arrhythmia	3
is	0
present	0
in	0
this	0
population	0
","	0
reversible	0
causes	0
must	0
be	0
identified	0
and	0
resolved	0
.	0
Thyroid	3
disorders	4
","	0
illicit	0
drug	0
or	0
stimulant	0
use	0
","	0
and	0
acute	3
alcohol	4
intoxication	4
are	0
among	0
these	0
causes	0
.	0
We	0
report	0
the	0
case	0
of	0
a	0
30	0
-	0
year	0
-	0
old	0
Caucasian	0
man	0
who	0
came	0
to	0
the	0
emergency	0
department	0
in	0
atrial	3
fibrillation	4
with	0
rapid	0
ventricular	0
response	0
.	0
His	0
medical	0
history	0
was	0
unremarkable	0
","	0
except	0
for	0
minor	0
fractures	3
of	0
the	0
fingers	0
and	0
foot	0
.	0
Thyroid	0
-	0
stimulating	0
hormone	0
","	0
magnesium	1
","	0
and	0
potassium	1
levels	0
were	0
within	0
normal	0
limits	0
","	0
urine	0
drug	0
screen	0
was	0
negative	0
","	0
and	0
alcohol	1
use	0
was	0
denied	0
.	0
However	0
","	0
when	0
the	0
patient	0
was	0
questioned	0
about	0
use	0
of	0
herbal	0
products	0
and	0
supplements	0
","	0
the	0
use	0
of	0
creatine	1
monohydrate	0
was	0
revealed	0
.	0
The	0
patient	0
was	0
admitted	0
to	0
the	0
hospital	0
","	0
anticoagulated	0
with	0
unfractionated	0
heparin	1
","	0
and	0
given	0
intravenous	0
diltiazem	1
for	0
rate	0
control	0
and	0
intravenous	0
amiodarone	1
for	0
rate	0
and	0
rhythm	0
control	0
.	0
When	0
discharged	0
less	0
than	0
24	0
hours	0
later	0
","	0
he	0
was	0
receiving	0
metoprolol	1
and	0
aspirin	1
","	0
with	0
follow	0
-	0
up	0
plans	0
for	0
echocardiography	0
and	0
nuclear	0
imaging	0
to	0
assess	0
perfusion	0
.	0
Exogenous	0
creatine	1
is	0
used	0
by	0
athletes	0
to	0
theoretically	0
improve	0
exercise	0
performance	0
.	0
Vegetarians	0
may	0
also	0
take	0
creatine	1
to	0
replace	0
what	0
they	0
are	0
not	0
consuming	0
from	0
meat	0
","	0
fish	0
","	0
and	0
other	0
animal	0
products	0
.	0
Previous	0
anecdotal	0
reports	0
have	0
linked	0
creatine	1
to	0
the	0
development	0
of	0
arrhythmia	3
.	0
Clinicians	0
must	0
be	0
diligent	0
when	0
interviewing	0
patients	0
about	0
their	0
drug	0
therapy	0
histories	0
and	0
include	0
questions	0
about	0
their	0
use	0
of	0
herbal	0
products	0
and	0
dietary	0
supplements	0
.	0
In	0
addition	0
","	0
it	0
is	0
important	0
to	0
report	0
adverse	0
effects	0
associated	0
with	0
frequently	0
consumed	0
supplements	0
and	0
herbal	0
products	0
to	0
the	0
Food	0
and	0
Drug	0
Administration	0
and	0
in	0
the	0
literature	0
.	0
Seizures	3
induced	0
by	0
the	0
cocaine	1
metabolite	0
benzoylecgonine	1
in	0
rats	0
.	0
The	0
half	0
-	0
life	0
(	0
t1	0
/	0
2	0
)	0
of	0
cocaine	1
is	0
relatively	0
short	0
","	0
but	0
some	0
of	0
the	0
consequences	0
of	0
its	0
use	0
","	0
such	0
as	0
seizures	3
and	0
strokes	3
","	0
can	0
occur	0
hours	0
after	0
exposure	0
.	0
This	0
led	0
us	0
to	0
hypothesize	0
that	0
a	0
metabolite	0
of	0
cocaine	1
may	0
be	0
responsible	0
for	0
some	0
of	0
those	0
delayed	0
sequelae	0
.	0
We	0
evaluated	0
the	0
potential	0
of	0
the	0
major	0
metabolite	0
of	0
cocaine	1
","	0
benzoylecgonine	1
(	0
BE	1
)	0
","	0
to	0
cause	0
seizures	3
.	0
Two	0
separate	0
equimolar	0
doses	0
(	0
0	0
.	0
2	0
and	0
0	0
.	0
4	0
mumol	0
)	0
of	0
either	0
cocaine	1
or	0
BE	1
were	0
injected	0
ventricularly	0
in	0
unanesthetized	0
juvenile	0
rats	0
.	0
Treated	0
rats	0
were	0
then	0
evaluated	0
for	0
incidence	0
","	0
latency	0
","	0
and	0
seizure	3
pattern	0
or	0
for	0
locomotor	0
activity	0
in	0
animals	0
without	0
seizures	3
.	0
BE	1
-	0
Induced	0
seizures	3
occurred	0
more	0
frequently	0
and	0
had	0
significantly	0
longer	0
latencies	0
than	0
those	0
induced	0
by	0
equimolar	0
amounts	0
of	0
cocaine	1
.	0
Whereas	0
cocaine	1
-	0
induced	0
seizures	3
were	0
best	0
characterized	0
as	0
brief	0
","	0
generalized	0
","	0
and	0
tonic	0
and	0
resulted	0
in	0
death	3
","	0
those	0
induced	0
by	0
BE	1
were	0
prolonged	0
","	0
often	0
multiple	0
and	0
mixed	0
in	0
type	0
","	0
and	0
rarely	0
resulted	0
in	0
death	3
.	0
Electrical	0
recordings	0
from	0
the	0
hippocampus	0
showed	0
a	0
rhythmic	0
progression	0
in	0
EEG	0
frequency	0
and	0
voltage	0
with	0
clinical	0
seizure	3
expression	0
.	0
BE	1
-	0
Injected	0
rats	0
that	0
did	0
not	0
have	0
seizures	3
had	0
significantly	0
more	0
locomotor	0
activity	0
than	0
cocaine	1
-	0
injected	0
animals	0
without	0
seizures	3
.	0
The	0
finding	0
that	0
cocaine	1
-	0
and	0
BE	1
-	0
induced	0
seizures	3
differ	0
in	0
several	0
respects	0
suggests	0
more	0
than	0
one	0
mechanism	0
for	0
cocaine	1
-	0
induced	0
seizures	3
and	0
emphasizes	0
the	0
importance	0
of	0
a	0
cocaine	1
metabolite	0
","	0
BE	1
.	0
The	0
selective	0
5	0
-	0
HT6	0
receptor	0
antagonist	0
Ro4368554	1
restores	0
memory	0
performance	0
in	0
cholinergic	0
and	0
serotonergic	0
models	0
of	0
memory	3
deficiency	4
in	0
the	0
rat	0
.	0
Antagonists	0
at	0
serotonin	1
type	0
6	0
(	0
5	1
-	2
HT	2
(	0
6	0
)	0
)	0
receptors	0
show	0
activity	0
in	0
models	0
of	0
learning	0
and	0
memory	0
.	0
Although	0
the	0
underlying	0
mechanism	0
(	0
s	0
)	0
are	0
not	0
well	0
understood	0
","	0
these	0
effects	0
may	0
involve	0
an	0
increase	0
in	0
acetylcholine	1
(	0
ACh	1
)	0
levels	0
.	0
The	0
present	0
study	0
sought	0
to	0
characterize	0
the	0
cognitive	0
-	0
enhancing	0
effects	0
of	0
the	0
5	1
-	2
HT	2
(	0
6	0
)	0
antagonist	0
Ro4368554	1
(	0
3	1
-	2
benzenesulfonyl	2
-	2
7	2
-	2
(	2
4	2
-	2
methyl	2
-	2
piperazin	2
-	2
1	2
-	2
yl	2
)	2
1H	2
-	2
indole	2
)	0
in	0
a	0
rat	0
object	0
recognition	0
task	0
employing	0
a	0
cholinergic	0
(	0
scopolamine	1
pretreatment	0
)	0
and	0
a	0
serotonergic	0
-	0
(	0
tryptophan	1
(	0
TRP	1
)	0
depletion	0
)	0
deficient	0
model	0
","	0
and	0
compared	0
its	0
pattern	0
of	0
action	0
with	0
that	0
of	0
the	0
acetylcholinesterase	0
inhibitor	0
metrifonate	1
.	0
Initial	0
testing	0
in	0
a	0
time	0
-	0
dependent	0
forgetting	0
task	0
employing	0
a	0
24	0
-	0
h	0
delay	0
between	0
training	0
and	0
testing	0
showed	0
that	0
metrifonate	1
improved	0
object	0
recognition	0
(	0
at	0
10	0
and	0
30	0
mg	0
/	0
kg	0
","	0
p	0
.	0
o	0
.	0
)	0
","	0
whereas	0
Ro4368554	1
was	0
inactive	0
.	0
Both	0
","	0
Ro4368554	1
(	0
3	0
and	0
10	0
mg	0
/	0
kg	0
","	0
intraperitoneally	0
(	0
i	0
.	0
p	0
.	0
)	0
)	0
and	0
metrifonate	1
(	0
10	0
mg	0
/	0
kg	0
","	0
p	0
.	0
o	0
.	0
","	0
respectively	0
)	0
reversed	0
memory	3
deficits	4
induced	0
by	0
scopolamine	1
and	0
TRP	1
depletion	0
(	0
10	0
mg	0
/	0
kg	0
","	0
i	0
.	0
p	0
.	0
","	0
and	0
3	0
mg	0
/	0
kg	0
","	0
p	0
.	0
o	0
.	0
","	0
respectively	0
)	0
.	0
In	0
conclusion	0
","	0
although	0
Ro4368554	1
did	0
not	0
improve	0
a	0
time	0
-	0
related	0
retention	0
deficit	0
","	0
it	0
reversed	0
a	0
cholinergic	0
and	0
a	0
serotonergic	0
memory	3
deficit	4
","	0
suggesting	0
that	0
both	0
mechanisms	0
may	0
be	0
involved	0
in	0
the	0
facilitation	0
of	0
object	0
memory	0
by	0
Ro4368554	1
and	0
","	0
possibly	0
","	0
other	0
5	1
-	2
HT	2
(	0
6	0
)	0
receptor	0
antagonists	0
.	0
Evaluation	0
of	0
the	0
anticocaine	0
monoclonal	0
antibody	0
GNC92H2	1
as	0
an	0
immunotherapy	0
for	0
cocaine	3
overdose	4
.	0
The	0
illicit	0
use	0
of	0
cocaine	1
continues	0
in	0
epidemic	0
proportions	0
and	0
treatment	0
for	0
cocaine	3
overdose	4
remains	0
elusive	0
.	0
Current	0
protein	0
-	0
based	0
technology	0
offers	0
a	0
new	0
therapeutic	0
venue	0
by	0
which	0
antibodies	0
bind	0
the	0
drug	0
in	0
the	0
blood	0
stream	0
","	0
inactivating	0
its	0
toxic	0
effects	0
.	0
The	0
therapeutic	0
potential	0
of	0
the	0
anticocaine	0
antibody	0
GNC92H2	1
was	0
examined	0
using	0
a	0
model	0
of	0
cocaine	3
overdose	4
.	0
Swiss	0
albino	0
mice	0
prepared	0
with	0
intrajugular	0
catheters	0
were	0
tested	0
in	0
photocell	0
cages	0
after	0
administration	0
of	0
93	0
mg	0
/	0
kg	0
(	0
LD50	0
)	0
of	0
cocaine	1
and	0
GNC92H2	1
infusions	0
ranging	0
from	0
30	0
to	0
190	0
mg	0
/	0
kg	0
.	0
GNC92H2	1
was	0
delivered	0
30	0
min	0
before	0
","	0
concomitantly	0
or	0
3	0
min	0
after	0
cocaine	1
treatment	0
.	0
Significant	0
blockade	0
of	0
cocaine	1
toxicity	3
was	0
observed	0
with	0
the	0
higher	0
dose	0
of	0
GNC92H2	1
(	0
190	0
mg	0
/	0
kg	0
)	0
","	0
where	0
premorbid	0
behaviors	0
were	0
reduced	0
up	0
to	0
40	0
%	0
","	0
seizures	3
up	0
to	0
77	0
%	0
and	0
death	3
by	0
72	0
%	0
.	0
Importantly	0
","	0
GNC92H2	1
prevented	0
death	3
even	0
post	0
-	0
cocaine	1
injection	0
.	0
The	0
results	0
support	0
the	0
important	0
potential	0
of	0
GNC92H2	1
as	0
a	0
therapeutic	0
tool	0
against	0
cocaine	3
overdose	4
.	0
Electrocardiographic	0
evidence	0
of	0
myocardial	3
injury	4
in	0
psychiatrically	0
hospitalized	0
cocaine	1
abusers	0
.	0
The	0
electrocardiograms	0
(	0
ECG	0
)	0
of	0
99	0
cocaine	1
-	0
abusing	0
patients	0
were	0
compared	0
with	0
the	0
ECGs	0
of	0
50	0
schizophrenic	3
controls	0
.	0
Eleven	0
of	0
the	0
cocaine	1
abusers	0
and	0
none	0
of	0
the	0
controls	0
had	0
ECG	0
evidence	0
of	0
significant	0
myocardial	3
injury	4
defined	0
as	0
myocardial	3
infarction	4
","	0
ischemia	3
","	0
and	0
bundle	3
branch	4
block	4
.	0
Behavioral	0
effects	0
of	0
urotensin	1
-	2
II	2
centrally	0
administered	0
in	0
mice	0
.	0
Urotensin	1
-	2
II	2
(	0
U	1
-	2
II	2
)	0
receptors	0
are	0
widely	0
distributed	0
in	0
the	0
central	0
nervous	0
system	0
.	0
Intracerebroventricular	0
(	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
injection	0
of	0
U	1
-	2
II	2
causes	0
hypertension	3
and	0
bradycardia	3
and	0
stimulates	0
prolactin	0
and	0
thyrotropin	0
secretion	0
.	0
However	0
","	0
the	0
behavioral	0
effects	0
of	0
centrally	0
administered	0
U	1
-	2
II	2
have	0
received	0
little	0
attention	0
.	0
In	0
the	0
present	0
study	0
","	0
we	0
tested	0
the	0
effects	0
of	0
i	0
.	0
c	0
.	0
v	0
.	0
injections	0
of	0
U	1
-	2
II	2
on	0
behavioral	0
","	0
metabolic	0
","	0
and	0
endocrine	0
responses	0
in	0
mice	0
.	0
Administration	0
of	0
graded	0
doses	0
of	0
U	1
-	2
II	2
(	0
1	0
-	0
10	0
","	0
0	0
ng	0
/	0
mouse	0
)	0
provoked	0
:	0
(	0
1	0
)	0
a	0
dose	0
-	0
dependent	0
reduction	0
in	0
the	0
number	0
of	0
head	0
dips	0
in	0
the	0
hole	0
-	0
board	0
test	0
;	0
(	0
2	0
)	0
a	0
dose	0
-	0
dependent	0
reduction	0
in	0
the	0
number	0
of	0
entries	0
in	0
the	0
white	0
chamber	0
in	0
the	0
black	0
-	0
and	0
-	0
white	0
compartment	0
test	0
","	0
and	0
in	0
the	0
number	0
of	0
entries	0
in	0
the	0
central	0
platform	0
and	0
open	0
arms	0
in	0
the	0
plus	0
-	0
maze	0
test	0
;	0
and	0
(	0
3	0
)	0
a	0
dose	0
-	0
dependent	0
increase	0
in	0
the	0
duration	0
of	0
immobility	0
in	0
the	0
forced	0
-	0
swimming	0
test	0
and	0
tail	0
suspension	0
test	0
.	0
Intracerebroventricular	0
injection	0
of	0
U	1
-	2
II	2
also	0
caused	0
an	0
increase	0
in	0
:	0
food	0
intake	0
at	0
doses	0
of	0
100	0
and	0
1	0
","	0
0	0
ng	0
/	0
mouse	0
","	0
water	0
intake	0
at	0
doses	0
of	0
100	0
-	0
10	0
","	0
0	0
ng	0
/	0
mouse	0
","	0
and	0
horizontal	0
locomotion	0
activity	0
at	0
a	0
dose	0
of	0
10	0
","	0
0	0
ng	0
/	0
mouse	0
.	0
Whatever	0
was	0
the	0
dose	0
","	0
the	0
central	0
administration	0
of	0
U	1
-	2
II	2
had	0
no	0
effect	0
on	0
body	0
temperature	0
","	0
nociception	0
","	0
apomorphine	1
-	0
induced	0
penile	3
erection	4
and	0
climbing	0
behavior	0
","	0
and	0
stress	0
-	0
induced	0
plasma	0
corticosterone	1
level	0
.	0
Taken	0
together	0
","	0
the	0
present	0
study	0
demonstrates	0
that	0
the	0
central	0
injection	0
of	0
U	1
-	2
II	2
at	0
doses	0
of	0
1	0
-	0
10	0
","	0
0	0
ng	0
/	0
mouse	0
induces	0
anxiogenic	0
-	0
and	0
depressant	0
-	0
like	0
effects	0
in	0
mouse	0
.	0
These	0
data	0
suggest	0
that	0
U	1
-	2
II	2
may	0
be	0
involved	0
in	0
some	0
aspects	0
of	0
psychiatric	3
disorders	4
.	0
Learning	0
of	0
rats	0
under	0
amnesia	3
caused	0
by	0
pentobarbital	1
.	0
Dissociated	0
learning	0
of	0
rats	0
in	0
the	0
normal	0
state	0
and	0
the	0
state	0
of	0
amnesia	3
produced	0
by	0
pentobarbital	1
(	0
15	0
mg	0
/	0
kg	0
","	0
ip	0
)	0
was	0
carried	0
out	0
.	0
Rats	0
were	0
trained	0
to	0
approach	0
a	0
shelf	0
where	0
they	0
received	0
food	0
reinforcement	0
.	0
In	0
Group	0
1	0
the	0
rats	0
were	0
trained	0
under	0
the	0
influence	0
of	0
pentobarbital	1
to	0
run	0
to	0
the	0
same	0
shelf	0
as	0
in	0
the	0
normal	0
state	0
.	0
In	0
Group	0
2	0
the	0
rats	0
were	0
trained	0
to	0
approach	0
different	0
shelves	0
in	0
different	0
drug	0
states	0
.	0
It	0
was	0
shown	0
that	0
memory	3
dissociation	4
occurred	0
in	0
both	0
groups	0
.	0
Differences	0
in	0
the	0
parameters	0
of	0
training	0
under	0
the	0
influence	0
of	0
pentobarbital	1
between	0
Groups	0
1	0
and	0
2	0
were	0
revealed	0
.	0
These	0
findings	0
show	0
that	0
the	0
brain	0
-	0
dissociated	0
state	0
induced	0
by	0
pentobarbital	1
is	0
formed	0
with	0
the	0
participation	0
of	0
the	0
mechanisms	0
of	0
information	0
perception	0
.	0
The	0
effects	0
of	0
short	0
-	0
term	0
raloxifene	1
therapy	0
on	0
fibrinolysis	0
markers	0
:	0
TAFI	0
","	0
tPA	0
","	0
and	0
PAI	0
-	0
1	0
.	0
BACKGR0UND	0
:	0
Markers	0
of	0
fibrinolysis	0
","	0
thrombin	0
-	0
activatable	0
fibrinolysis	0
inhibitor	0
(	0
TAFI	0
)	0
","	0
tissue	0
-	0
type	0
plasminogen	0
activator	0
(	0
tPA	0
)	0
","	0
and	0
plasminogen	0
activator	0
inhibitor	0
-	0
1	0
(	0
PAI	0
-	0
1	0
)	0
levels	0
were	0
studied	0
for	0
the	0
evaluation	0
of	0
short	0
-	0
term	0
effects	0
of	0
raloxifene	1
administration	0
in	0
postmenopausal	0
women	0
.	0
METH0DS	0
:	0
Thirty	0
-	0
nine	0
postmenopausal	0
women	0
with	0
osteopenia	3
or	0
osteoporosis	3
were	0
included	0
in	0
this	0
prospective	0
","	0
controlled	0
clinical	0
study	0
.	0
Twenty	0
-	0
five	0
women	0
were	0
given	0
raloxifene	1
hydrochloride	2
(	0
60	0
mg	0
/	0
day	0
)	0
plus	0
calcium	1
(	0
500	0
mg	0
/	0
day	0
)	0
.	0
Age	0
-	0
matched	0
controls	0
(	0
n	0
=	0
14	0
)	0
were	0
given	0
only	0
calcium	1
.	0
Plasma	0
TAFI	0
","	0
tPA	0
","	0
and	0
PAI	0
-	0
1	0
antigen	0
levels	0
were	0
measured	0
at	0
baseline	0
and	0
after	0
3	0
months	0
of	0
treatment	0
by	0
commercially	0
available	0
ELISA	0
kits	0
.	0
Variations	0
of	0
individuals	0
were	0
assessed	0
by	0
Wilcoxon	0
'	0
s	0
test	0
.	0
Relationship	0
between	0
those	0
markers	0
and	0
demographic	0
characteristics	0
were	0
investigated	0
.	0
RESULTS	0
:	0
Three	0
months	0
of	0
raloxifene	1
treatment	0
was	0
associated	0
with	0
a	0
significant	0
decrease	0
in	0
the	0
plasma	0
TAFI	0
antigen	0
concentrations	0
(	0
16	0
%	0
change	0
","	0
P	0
<	0
0	0
.	0
1	0
)	0
","	0
and	0
a	0
significant	0
increase	0
in	0
tPA	0
antigen	0
concentrations	0
(	0
25	0
%	0
change	0
","	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
A	0
significant	0
correlation	0
was	0
found	0
between	0
baseline	0
TAFI	0
antigen	0
concentrations	0
and	0
the	0
duration	0
of	0
amenorrhea	3
(	0
P	0
<	0
0	0
.	0
5	0
;	0
r	0
=	0
0	0
.	0
33	0
)	0
.	0
C0NCLUSI0N	0
:	0
We	0
suggest	0
that	0
the	0
increased	0
risk	0
of	0
venous	3
thromboembolism	4
due	0
to	0
raloxifene	1
treatment	0
may	0
be	0
related	0
to	0
increased	0
tPA	0
levels	0
","	0
but	0
not	0
TAFI	0
levels	0
.	0
Valproate	1
-	0
induced	0
encephalopathy	3
.	0
Valproate	1
-	0
induced	0
encephalopathy	3
is	0
a	0
rare	0
syndrome	0
that	0
may	0
manifest	0
in	0
otherwise	0
normal	0
epileptic	3
individuals	0
.	0
It	0
may	0
even	0
present	0
in	0
patients	0
who	0
have	0
tolerated	0
this	0
medicine	0
well	0
in	0
the	0
past	0
.	0
It	0
is	0
usually	0
but	0
not	0
necessarily	0
associated	0
with	0
hyperammonemia	3
.	0
The	0
EEG	0
shows	0
characteristic	0
triphasic	0
waves	0
in	0
most	0
patients	0
with	0
this	0
complication	0
.	0
A	0
case	0
of	0
valproate	1
-	0
induced	0
encephalopathy	3
is	0
presented	0
.	0
The	0
problems	0
in	0
diagnosing	0
this	0
condition	0
are	0
subsequently	0
discussed	0
.	0
Recurrent	0
dysphonia	3
and	0
acitretin	1
.	0
We	0
report	0
the	0
case	0
of	0
a	0
woman	0
complaining	0
of	0
dysphonia	3
while	0
she	0
was	0
treated	0
by	0
acitretin	1
.	0
Her	0
symptoms	0
totally	0
regressed	0
after	0
drug	0
withdrawal	0
and	0
reappeared	0
when	0
acitretin	1
was	0
reintroduced	0
.	0
To	0
our	0
knowledge	0
","	0
this	0
is	0
the	0
first	0
case	0
of	0
acitretin	1
-	0
induced	0
dysphonia	3
.	0
This	0
effect	0
may	0
be	0
related	0
to	0
the	0
pharmacological	0
effect	0
of	0
this	0
drug	0
on	0
mucous	0
membranes	0
.	0
Nitro	1
-	2
L	2
-	2
arginine	2
methyl	2
ester	2
:	0
a	0
potential	0
protector	0
against	0
gentamicin	1
ototoxicity	3
.	0
The	0
nitric	1
oxide	2
(	0
N0	1
)	0
inhibitor	0
nitro	1
-	2
L	2
-	2
arginine	2
methyl	2
ester	2
(	0
L	1
-	2
NAME	2
)	0
may	0
act	0
as	0
an	0
otoprotectant	0
against	0
high	3
-	4
frequency	4
hearing	4
loss	4
caused	0
by	0
gentamicin	1
","	0
but	0
further	0
studies	0
are	0
needed	0
to	0
confirm	0
this	0
.	0
Aminoglycoside	1
antibiotics	0
are	0
still	0
widely	0
used	0
by	0
virtue	0
of	0
their	0
efficacy	0
and	0
low	0
cost	0
.	0
Their	0
ototoxicity	3
is	0
a	0
serious	0
health	0
problem	0
and	0
","	0
as	0
their	0
ototoxic	3
mechanism	0
involves	0
the	0
production	0
of	0
N0	1
","	0
we	0
need	0
to	0
assess	0
the	0
use	0
of	0
N0	1
inhibitors	0
for	0
the	0
prevention	0
of	0
aminoglycoside	1
-	0
induced	0
sensorineural	3
hearing	4
loss	4
.	0
In	0
this	0
experimental	0
study	0
we	0
used	0
30	0
Sprague	0
-	0
Dawley	0
rats	0
","	0
27	0
of	0
which	0
had	0
gentamicin	1
instilled	0
into	0
the	0
middle	0
ear	0
.	0
The	0
otoprotectant	0
L	1
-	2
NAME	2
was	0
administered	0
topically	0
to	0
12	0
/	0
27	0
animals	0
.	0
Its	0
effect	0
was	0
determined	0
in	0
terms	0
of	0
attenuation	0
of	0
hearing	3
loss	4
","	0
measured	0
by	0
shifts	0
in	0
the	0
auditory	0
brainstem	0
response	0
threshold	0
.	0
L	1
-	2
NAME	2
reduced	0
gentamicin	1
-	0
induced	0
hearing	3
loss	4
in	0
the	0
high	0
-	0
frequency	0
range	0
","	0
but	0
gave	0
no	0
protection	0
in	0
the	0
middle	0
or	0
low	0
frequencies	0
.	0
Safety	0
profile	0
of	0
a	0
nicotine	1
lozenge	0
compared	0
with	0
that	0
of	0
nicotine	1
gum	0
in	0
adult	0
smokers	0
with	0
underlying	0
medical	0
conditions	0
:	0
a	0
12	0
-	0
week	0
","	0
randomized	0
","	0
open	0
-	0
label	0
study	0
.	0
BACKGR0UND	0
:	0
Nicotine	1
polacrilex	0
lozenges	0
deliver	0
25	0
%	0
to	0
27	0
%	0
more	0
nicotine	1
compared	0
with	0
equivalent	0
doses	0
of	0
nicotine	1
polacrilex	0
gum	0
.	0
The	0
increased	0
nicotine	1
exposure	0
from	0
the	0
lozenge	0
has	0
raised	0
questions	0
about	0
the	0
relative	0
safety	0
of	0
the	0
lozenge	0
and	0
gum	0
.	0
0BJECTIVE	0
:	0
The	0
objective	0
of	0
this	0
study	0
was	0
to	0
compare	0
the	0
safety	0
profiles	0
of	0
the	0
4	0
-	0
mg	0
nicotine	1
lozenge	0
and	0
4	0
-	0
mg	0
nicotine	1
gum	0
in	0
smokers	0
with	0
selected	0
label	0
-	0
restricted	0
diseases	0
.	0
METH0DS	0
:	0
This	0
was	0
a	0
multicenter	0
","	0
randomized	0
","	0
open	0
-	0
label	0
study	0
in	0
adult	0
smokers	0
with	0
heart	3
disease	4
","	0
hypertension	3
not	0
controlled	0
by	0
medication	0
","	0
and	0
/	0
or	0
diabetes	3
mellitus	4
.	0
Patients	0
were	0
randomized	0
in	0
a	0
1	0
:	0
1	0
ratio	0
to	0
receive	0
the	0
4	0
-	0
mg	0
nicotine	1
lozenge	0
or	0
4	0
-	0
mg	0
nicotine	1
gum	0
.	0
Safety	0
assessments	0
were	0
made	0
at	0
baseline	0
and	0
at	0
2	0
","	0
4	0
","	0
6	0
","	0
and	0
12	0
weeks	0
after	0
the	0
start	0
of	0
product	0
use	0
.	0
RESULTS	0
:	0
Nine	0
hundred	0
one	0
patients	0
were	0
randomized	0
to	0
treatment	0
","	0
447	0
who	0
received	0
the	0
lozenge	0
and	0
454	0
who	0
received	0
the	0
gum	0
(	0
safety	0
population	0
)	0
.	0
The	0
majority	0
were	0
women	0
(	0
52	0
.	0
7	0
%	0
)	0
.	0
Patients	0
'	0
mean	0
age	0
was	0
53	0
.	0
9	0
years	0
","	0
their	0
mean	0
weight	0
was	0
193	0
.	0
9	0
pounds	0
","	0
and	0
they	0
smoked	0
a	0
mean	0
of	0
25	0
.	0
2	0
cigarettes	0
per	0
day	0
at	0
baseline	0
.	0
Five	0
hundred	0
fifty	0
-	0
three	0
patients	0
","	0
264	0
taking	0
the	0
lozenge	0
and	0
289	0
taking	0
the	0
gum	0
","	0
used	0
the	0
study	0
product	0
for	0
>	0
or	0
=	0
4	0
days	0
per	0
week	0
during	0
the	0
first	0
2	0
weeks	0
(	0
evaluable	0
population	0
)	0
.	0
The	0
nicotine	1
lozenge	0
and	0
nicotine	1
gum	0
were	0
equally	0
well	0
tolerated	0
","	0
despite	0
increased	0
nicotine	1
exposure	0
from	0
the	0
lozenge	0
.	0
The	0
incidence	0
of	0
adverse	0
events	0
in	0
the	0
2	0
groups	0
was	0
similar	0
during	0
the	0
first	0
2	0
weeks	0
of	0
product	0
use	0
(	0
evaluation	0
population	0
:	0
55	0
.	0
3	0
%	0
lozenge	0
","	0
54	0
.	0
7	0
%	0
gum	0
)	0
","	0
as	0
well	0
as	0
during	0
the	0
entire	0
study	0
(	0
safety	0
population	0
:	0
63	0
.	0
8	0
%	0
and	0
58	0
.	0
6	0
%	0
","	0
respectively	0
)	0
.	0
Stratification	0
of	0
patients	0
by	0
sex	0
","	0
age	0
","	0
extent	0
of	0
concurrent	0
smoking	0
","	0
extent	0
of	0
product	0
use	0
","	0
and	0
severity	0
of	0
adverse	0
events	0
revealed	0
no	0
clinically	0
significant	0
differences	0
between	0
the	0
lozenge	0
and	0
gum	0
.	0
The	0
most	0
common	0
adverse	0
events	0
were	0
nausea	3
(	0
17	0
.	0
2	0
%	0
and	0
16	0
.	0
1	0
%	0
;	0
95	0
%	0
CI	0
","	0
-	0
3	0
.	0
7	0
to	0
6	0
.	0
0	0
)	0
","	0
hiccups	3
(	0
10	0
.	0
7	0
%	0
and	0
6	0
.	0
6	0
%	0
;	0
95	0
%	0
CI	0
","	0
0	0
.	0
5	0
to	0
7	0
.	0
8	0
)	0
","	0
and	0
headache	3
(	0
8	0
.	0
7	0
%	0
and	0
9	0
.	0
9	0
%	0
;	0
95	0
%	0
Cl	0
","	0
-	0
5	0
.	0
0	0
to	0
2	0
.	0
6	0
)	0
.	0
Serious	0
adverse	0
events	0
were	0
reported	0
in	0
11	0
and	0
13	0
patients	0
in	0
the	0
respective	0
groups	0
.	0
Fewer	0
than	0
6	0
%	0
of	0
patients	0
in	0
either	0
group	0
were	0
considered	0
by	0
the	0
investigator	0
to	0
have	0
a	0
worsening	0
of	0
their	0
overall	0
disease	0
condition	0
during	0
the	0
study	0
.	0
The	0
majority	0
of	0
patients	0
(	0
>	0
60	0
%	0
)	0
experienced	0
no	0
change	0
in	0
their	0
disease	0
status	0
from	0
baseline	0
.	0
C0NCLUSI0N	0
:	0
The	0
4	0
-	0
mg	0
nicotine	1
lozenge	0
and	0
4	0
-	0
mg	0
nicotine	1
gum	0
had	0
comparable	0
safety	0
profiles	0
in	0
these	0
patients	0
with	0
label	0
-	0
restricted	0
medical	0
conditions	0
.	0
Pharmacological	0
modulation	0
of	0
pain	3
-	0
related	0
brain	0
activity	0
during	0
normal	0
and	0
central	0
sensitization	0
states	0
in	0
humans	0
.	0
Abnormal	0
processing	0
of	0
somatosensory	0
inputs	0
in	0
the	0
central	0
nervous	0
system	0
(	0
central	0
sensitization	0
)	0
is	0
the	0
mechanism	0
accounting	0
for	0
the	0
enhanced	0
pain	3
sensitivity	0
in	0
the	0
skin	0
surrounding	0
tissue	3
injury	4
(	0
secondary	3
hyperalgesia	4
)	0
.	0
Secondary	3
hyperalgesia	4
shares	0
clinical	0
characteristics	0
with	0
neurogenic	3
hyperalgesia	4
in	0
patients	0
with	0
neuropathic	3
pain	4
.	0
Abnormal	0
brain	0
responses	0
to	0
somatosensory	0
stimuli	0
have	0
been	0
found	0
in	0
patients	0
with	0
hyperalgesia	3
as	0
well	0
as	0
in	0
normal	0
subjects	0
during	0
experimental	0
central	0
sensitization	0
.	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
assess	0
the	0
effects	0
of	0
gabapentin	1
","	0
a	0
drug	0
effective	0
in	0
neuropathic	3
pain	4
patients	0
","	0
on	0
brain	0
processing	0
of	0
nociceptive	0
information	0
in	0
normal	0
and	0
central	0
sensitization	0
states	0
.	0
Using	0
functional	0
magnetic	0
resonance	0
imaging	0
(	0
fMRI	0
)	0
in	0
normal	0
volunteers	0
","	0
we	0
studied	0
the	0
gabapentin	1
-	0
induced	0
modulation	0
of	0
brain	0
activity	0
in	0
response	0
to	0
nociceptive	0
mechanical	0
stimulation	0
of	0
normal	0
skin	0
and	0
capsaicin	1
-	0
induced	0
secondary	3
hyperalgesia	4
.	0
The	0
dose	0
of	0
gabapentin	1
was	0
1	0
","	0
800	0
mg	0
per	0
os	0
","	0
in	0
a	0
single	0
administration	0
.	0
We	0
found	0
that	0
(	0
i	0
)	0
gabapentin	1
reduced	0
the	0
activations	0
in	0
the	0
bilateral	0
operculoinsular	0
cortex	0
","	0
independently	0
of	0
the	0
presence	0
of	0
central	0
sensitization	0
;	0
(	0
ii	0
)	0
gabapentin	1
reduced	0
the	0
activation	0
in	0
the	0
brainstem	0
","	0
only	0
during	0
central	0
sensitization	0
;	0
(	0
iii	0
)	0
gabapentin	1
suppressed	0
stimulus	0
-	0
induced	0
deactivations	0
","	0
only	0
during	0
central	0
sensitization	0
;	0
this	0
effect	0
was	0
more	0
robust	0
than	0
the	0
effect	0
on	0
brain	0
activation	0
.	0
The	0
observed	0
drug	0
-	0
induced	0
effects	0
were	0
not	0
due	0
to	0
changes	0
in	0
the	0
baseline	0
fMRI	0
signal	0
.	0
These	0
findings	0
indicate	0
that	0
gabapentin	1
has	0
a	0
measurable	0
antinociceptive	0
effect	0
and	0
a	0
stronger	0
antihyperalgesic	0
effect	0
most	0
evident	0
in	0
the	0
brain	0
areas	0
undergoing	0
deactivation	0
","	0
thus	0
supporting	0
the	0
concept	0
that	0
gabapentin	1
is	0
more	0
effective	0
in	0
modulating	0
nociceptive	0
transmission	0
when	0
central	0
sensitization	0
is	0
present	0
.	0
Investigation	0
of	0
mitochondrial	0
involvement	0
in	0
the	0
experimental	0
model	0
of	0
epilepsy	3
induced	0
by	0
pilocarpine	1
.	0
Mitochondrial	3
abnormalities	4
have	0
been	0
associated	0
with	0
several	0
aspects	0
of	0
epileptogenesis	0
","	0
such	0
as	0
energy	0
generation	0
","	0
control	0
of	0
cell	0
death	3
","	0
neurotransmitter	0
synthesis	0
","	0
and	0
free	0
radical	0
(	0
FR	0
)	0
production	0
.	0
Increased	0
production	0
of	0
FRs	0
may	0
cause	0
mtDNA	0
damage	0
leading	0
to	0
decreased	0
activities	0
of	0
oxidative	0
phosphorylation	0
complexes	0
containing	0
mtDNA	0
-	0
encoded	0
subunits	0
.	0
In	0
this	0
study	0
","	0
we	0
investigated	0
whether	0
increased	0
generation	0
of	0
FR	0
during	0
status	3
epilepticus	4
would	0
be	0
sufficient	0
to	0
provoke	0
abnormalities	0
in	0
mtDNA	0
and	0
in	0
the	0
expression	0
and	0
activity	0
of	0
cytochrome	0
c	0
oxidase	0
(	0
CC0	0
)	0
","	0
complex	0
IV	0
of	0
the	0
respiratory	0
chain	0
","	0
in	0
the	0
chronic	0
phase	0
of	0
the	0
pilocarpine	1
model	0
of	0
temporal	3
lobe	4
epilepsy	4
.	0
DNA	0
analysis	0
revealed	0
low	0
amounts	0
of	0
a	0
4	0
.	0
8	0
kb	0
mtDNA	0
deletion	0
but	0
with	0
no	0
differences	0
in	0
frequency	0
or	0
quantity	0
in	0
the	0
control	0
and	0
experimental	0
groups	0
.	0
We	0
did	0
not	0
find	0
abnormalities	0
in	0
the	0
expression	0
and	0
distribution	0
of	0
an	0
mtDNA	0
-	0
encoded	0
subunit	0
of	0
CC0	0
(	0
CC0	0
-	0
I	0
)	0
or	0
a	0
relative	0
decrease	0
in	0
CC0	0
-	0
I	0
when	0
compared	0
with	0
nuclear	0
-	0
encoded	0
subunits	0
(	0
CC0	0
-	0
IV	0
and	0
SDH	0
-	0
fp	0
)	0
.	0
No	0
abnormality	0
in	0
CC0	0
activity	0
was	0
observed	0
through	0
histochemistry	0
.	0
Although	0
evidences	0
of	0
mitochondrial	3
abnormalities	4
were	0
found	0
in	0
previously	0
published	0
studies	0
","	0
our	0
results	0
do	0
not	0
suggest	0
that	0
the	0
FRs	0
","	0
generated	0
during	0
the	0
acute	0
phase	0
","	0
determined	0
important	0
abnormalities	0
in	0
mtDNA	0
","	0
in	0
expression	0
of	0
CC0	0
-	0
I	0
","	0
and	0
in	0
CC0	0
activity	0
.	0
Adverse	0
effect	0
of	0
the	0
calcium	1
channel	0
blocker	0
nitrendipine	1
on	0
nephrosclerosis	3
in	0
rats	0
with	0
renovascular	3
hypertension	4
.	0
The	0
effect	0
of	0
a	0
6	0
-	0
week	0
treatment	0
with	0
the	0
calcium	1
channel	0
blocker	0
nitrendipine	1
or	0
the	0
angiotensin	1
converting	0
enzyme	0
inhibitor	0
enalapril	1
on	0
blood	0
pressure	0
","	0
albuminuria	3
","	0
renal	0
hemodynamics	0
","	0
and	0
morphology	0
of	0
the	0
nonclipped	0
kidney	0
was	0
studied	0
in	0
rats	0
with	0
two	0
-	0
kidney	0
","	0
one	0
clip	0
renovascular	3
hypertension	4
.	0
Six	0
weeks	0
after	0
clipping	0
of	0
one	0
renal	0
artery	0
","	0
hypertensive	3
rats	0
(	0
178	0
+	0
/	0
-	0
4	0
mm	0
Hg	0
)	0
were	0
randomly	0
assigned	0
to	0
three	0
groups	0
:	0
untreated	0
hypertensive	3
controls	0
(	0
n	0
=	0
8	0
)	0
","	0
enalapril	1
-	0
treated	0
(	0
n	0
=	0
8	0
)	0
","	0
or	0
nitrendipine	1
-	0
treated	0
(	0
n	0
=	0
10	0
)	0
.	0
Sham	0
-	0
operated	0
rats	0
served	0
as	0
normotensive	0
controls	0
(	0
128	0
+	0
/	0
-	0
3	0
mm	0
Hg	0
","	0
n	0
=	0
8	0
)	0
.	0
After	0
6	0
weeks	0
of	0
treatment	0
","	0
renal	0
hemodynamics	0
(	0
glomerular	0
filtration	0
rate	0
and	0
renal	0
plasma	0
flow	0
)	0
were	0
measured	0
in	0
the	0
anesthetized	0
rats	0
.	0
Renal	0
tissue	0
was	0
obtained	0
for	0
determination	0
of	0
glomerular	0
size	0
and	0
sclerosis	0
.	0
Enalapril	1
but	0
not	0
nitrendipine	1
reduced	0
blood	0
pressure	0
significantly	0
.	0
After	0
6	0
weeks	0
of	0
therapy	0
","	0
glomerular	0
filtration	0
rate	0
was	0
not	0
different	0
among	0
the	0
studied	0
groups	0
.	0
Renal	0
plasma	0
flow	0
increased	0
","	0
but	0
albumin	0
excretion	0
and	0
glomerulosclerosis	3
did	0
not	0
change	0
after	0
enalapril	1
treatment	0
.	0
In	0
contrast	0
","	0
in	0
the	0
nitrendipine	1
-	0
treated	0
group	0
albuminuria	3
increased	0
from	0
12	0
.	0
8	0
+	0
/	0
-	0
2	0
progressively	0
to	0
163	0
+	0
/	0
-	0
55	0
compared	0
with	0
19	0
.	0
2	0
+	0
/	0
-	0
9	0
mg	0
/	0
24	0
hr	0
in	0
the	0
hypertensive	3
controls	0
.	0
Furthermore	0
","	0
glomerulosclerosis	3
index	0
was	0
significantly	0
increased	0
in	0
the	0
nitrendipine	1
-	0
treated	0
group	0
compared	0
with	0
the	0
hypertensive	3
controls	0
(	0
0	0
.	0
38	0
+	0
/	0
-	0
0	0
.	0
1	0
versus	0
0	0
.	0
13	0
+	0
/	0
-	0
0	0
.	0
4	0
)	0
.	0
In	0
addition	0
","	0
glomerular	0
size	0
was	0
higher	0
in	0
the	0
nitrendipine	1
-	0
treated	0
group	0
(	0
14	0
.	0
9	0
+	0
/	0
-	0
0	0
.	0
17	0
10	0
(	0
-	0
3	0
)	0
mm2	0
)	0
but	0
lower	0
in	0
the	0
enalapril	1
-	0
treated	0
group	0
(	0
11	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
15	0
10	0
(	0
-	0
3	0
)	0
mm2	0
)	0
compared	0
with	0
the	0
hypertensive	3
controls	0
(	0
12	0
.	0
1	0
+	0
/	0
-	0
0	0
.	0
17	0
10	0
(	0
-	0
3	0
)	0
mm2	0
)	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0
Ketoconazole	1
induced	0
torsades	3
de	4
pointes	4
without	0
concomitant	0
use	0
of	0
QT	0
interval	0
-	0
prolonging	0
drug	0
.	0
Ketoconazole	1
is	0
not	0
known	0
to	0
be	0
proarrhythmic	0
without	0
concomitant	0
use	0
of	0
QT	0
interval	0
-	0
prolonging	0
drugs	0
.	0
We	0
report	0
a	0
woman	0
with	0
coronary	3
artery	4
disease	4
who	0
developed	0
a	0
markedly	0
prolonged	3
QT	4
interval	4
and	0
torsades	3
de	4
pointes	4
(	0
TdP	3
)	0
after	0
taking	0
ketoconazole	1
for	0
treatment	0
of	0
fungal	3
infection	4
.	0
Her	0
QT	0
interval	0
returned	0
to	0
normal	0
upon	0
withdrawal	0
of	0
ketoconazole	1
.	0
Genetic	0
study	0
did	0
not	0
find	0
any	0
mutation	0
in	0
her	0
genes	0
that	0
encode	0
cardiac	0
IKr	0
channel	0
proteins	0
.	0
We	0
postulate	0
that	0
by	0
virtue	0
of	0
its	0
direct	0
blocking	0
action	0
on	0
IKr	0
","	0
ketoconazole	1
alone	0
may	0
prolong	0
QT	0
interval	0
and	0
induce	0
TdP	3
.	0
This	0
calls	0
for	0
attention	0
when	0
ketoconazole	1
is	0
administered	0
to	0
patients	0
with	0
risk	0
factors	0
for	0
acquired	0
long	3
QT	4
syndrome	4
.	0
Cerebral	3
vasculitis	4
following	0
oral	0
methylphenidate	1
intake	0
in	0
an	0
adult	0
:	0
a	0
case	0
report	0
.	0
Methylphenidate	1
is	0
structurally	0
and	0
functionally	0
similar	0
to	0
amphetamine	1
.	0
Cerebral	3
vasculitis	4
associated	0
with	0
amphetamine	3
abuse	4
is	0
well	0
documented	0
","	0
and	0
in	0
rare	0
cases	0
ischaemic	3
stroke	4
has	0
been	0
reported	0
after	0
methylphenidate	1
intake	0
in	0
children	0
.	0
We	0
report	0
the	0
case	0
of	0
a	0
63	0
-	0
year	0
-	0
old	0
female	0
who	0
was	0
treated	0
with	0
methylphenidate	1
due	0
to	0
hyperactivity	3
and	0
suffered	0
from	0
multiple	0
ischaemic	3
strokes	4
.	0
We	0
consider	0
drug	0
-	0
induced	0
cerebral	3
vasculitis	4
as	0
the	0
most	0
likely	0
cause	0
of	0
recurrent	0
ischaemic	3
strokes	4
in	0
the	0
absence	0
of	0
any	0
pathological	0
findings	0
during	0
the	0
diagnostic	0
work	0
-	0
up	0
.	0
We	0
conclude	0
that	0
methylphenidate	1
mediated	0
vasculitis	3
should	0
be	0
considered	0
in	0
patients	0
with	0
neurological	0
symptoms	0
and	0
a	0
history	0
of	0
methylphenidate	1
therapy	0
.	0
This	0
potential	0
side	0
-	0
effect	0
","	0
though	0
very	0
rare	0
","	0
represents	0
one	0
more	0
reason	0
to	0
be	0
very	0
restrictive	0
in	0
the	0
use	0
of	0
methylphenidate	1
.	0
MDMA	1
polydrug	0
users	0
show	0
process	0
-	0
specific	0
central	0
executive	0
impairments	0
coupled	0
with	0
impaired	3
social	4
and	4
emotional	4
judgement	4
processes	4
.	0
In	0
recent	0
years	0
working	0
memory	3
deficits	4
have	0
been	0
reported	0
in	0
users	0
of	0
MDMA	1
(	0
3	1
","	2
4	2
-	2
methylenedioxymethamphetamine	2
","	0
ecstasy	1
)	0
.	0
The	0
current	0
study	0
aimed	0
to	0
assess	0
the	0
impact	0
of	0
MDMA	1
use	0
on	0
three	0
separate	0
central	0
executive	0
processes	0
(	0
set	0
shifting	0
","	0
inhibition	0
and	0
memory	0
updating	0
)	0
and	0
also	0
on	0
"	0
prefrontal	0
"	0
mediated	0
social	0
and	0
emotional	0
judgement	0
processes	0
.	0
Fifteen	0
polydrug	0
ecstasy	1
users	0
and	0
15	0
polydrug	0
non	0
-	0
ecstasy	1
user	0
controls	0
completed	0
a	0
general	0
drug	0
use	0
questionnaire	0
","	0
the	0
Brixton	0
Spatial	0
Anticipation	0
task	0
(	0
set	0
shifting	0
)	0
","	0
Backward	0
Digit	0
Span	0
procedure	0
(	0
memory	0
updating	0
)	0
","	0
Inhibition	0
of	0
Return	0
(	0
inhibition	0
)	0
","	0
an	0
emotional	0
intelligence	0
scale	0
","	0
the	0
Tromso	0
Social	0
Intelligence	0
Scale	0
and	0
the	0
Dysexecutive	0
Questionnaire	0
(	0
DEX	0
)	0
.	0
Compared	0
with	0
MDMA	1
-	0
free	0
polydrug	0
controls	0
","	0
MDMA	1
polydrug	0
users	0
showed	0
impairments	0
in	0
set	0
shifting	0
and	0
memory	0
updating	0
","	0
and	0
also	0
in	0
social	0
and	0
emotional	0
judgement	0
processes	0
.	0
The	0
latter	0
two	0
deficits	0
remained	0
significant	0
after	0
controlling	0
for	0
other	0
drug	0
use	0
.	0
These	0
data	0
lend	0
further	0
support	0
to	0
the	0
proposal	0
that	0
cognitive	0
processes	0
mediated	0
by	0
the	0
prefrontal	0
cortex	0
may	0
be	0
impaired	0
by	0
recreational	0
ecstasy	1
use	0
.	0
Phase	0
II	0
study	0
of	0
the	0
amsacrine	1
analogue	0
CI	1
-	2
921	2
(	0
NSC	1
343499	2
)	0
in	0
non	3
-	4
small	4
cell	4
lung	4
cancer	4
.	0
CI	1
-	2
921	2
(	0
NSC	1
343499	2
;	0
9	1
-	2
[	2
[	2
2	2
-	2
methoxy	2
-	2
4	2
-	2
[	2
(	2
methylsulphonyl	2
)	2
amino	2
]	2
phenyl	2
]	2
amino	2
]	2
-	2
N	2
","	2
5	2
-	2
dimethyl	2
-	2
4	2
-	2
acridinecarboxamide	2
)	0
is	0
a	0
topoisomerase	0
II	0
poison	0
with	0
high	0
experimental	0
antitumour	0
activity	0
.	0
It	0
was	0
administered	0
by	0
15	0
min	0
infusion	0
to	0
16	0
evaluable	0
patients	0
with	0
non	3
-	4
small	4
cell	4
lung	4
cancer	4
(	0
NSCLC	3
)	0
(	0
7	0
with	0
no	0
prior	0
treatment	0
","	0
9	0
patients	0
in	0
relapse	0
following	0
surgery	0
/	0
radiotherapy	0
)	0
at	0
a	0
dose	0
(	0
648	0
mg	0
/	0
m2	0
divided	0
over	0
3	0
days	0
","	0
repeated	0
every	0
3	0
weeks	0
)	0
determined	0
by	0
phase	0
I	0
trial	0
.	0
Patients	0
had	0
a	0
median	0
performance	0
status	0
of	0
1	0
(	0
WH0	0
)	0
","	0
and	0
median	0
age	0
of	0
61	0
years	0
.	0
The	0
histology	0
comprised	0
squamous	3
carcinoma	4
(	0
11	0
)	0
","	0
adenocarcinoma	3
(	0
1	0
)	0
","	0
mixed	0
histology	0
(	0
2	0
)	0
","	0
bronchio	3
-	4
alveolar	4
carcinoma	4
(	0
1	0
)	0
and	0
large	0
cell	0
undifferentiated	3
carcinoma	4
(	0
1	0
)	0
.	0
Neutropenia	3
grade	0
greater	0
than	0
or	0
equal	0
to	0
3	0
was	0
seen	0
in	0
15	0
patients	0
","	0
infections	3
with	0
recovery	0
in	0
3	0
","	0
and	0
grand	0
mal	0
seizures	3
in	0
1	0
patient	0
.	0
Grade	0
less	0
than	0
or	0
equal	0
to	0
2	0
nausea	3
and	0
vomiting	3
occurred	0
in	0
66	0
%	0
courses	0
and	0
phlebitis	3
in	0
the	0
infusion	0
arm	0
in	0
37	0
%	0
.	0
1	0
patient	0
with	0
squamous	3
cell	4
carcinoma	4
achieved	0
a	0
partial	0
response	0
lasting	0
5	0
months	0
.	0
Further	0
testing	0
in	0
this	0
and	0
other	0
tumour	3
types	0
using	0
multiple	0
daily	0
schedules	0
is	0
warranted	0
.	0
Pharmacokinetics	0
of	0
desipramine	1
HCl	2
when	0
administered	0
with	0
cinacalcet	1
HCl	2
.	0
0BJECTIVE	0
:	0
In	0
vitro	0
work	0
has	0
demonstrated	0
that	0
cinacalcet	1
is	0
a	0
strong	0
inhibitor	0
of	0
cytochrome	0
P450	0
isoenzyme	0
(	0
CYP	0
)	0
2D6	0
.	0
The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
evaluate	0
the	0
effect	0
of	0
cinacalcet	1
on	0
CYP2D6	0
activity	0
","	0
using	0
desipramine	1
as	0
a	0
probe	0
substrate	0
","	0
in	0
healthy	0
subjects	0
.	0
METH0DS	0
:	0
Seventeen	0
subjects	0
who	0
were	0
genotyped	0
as	0
CYP2D6	0
extensive	0
metabolizers	0
were	0
enrolled	0
in	0
this	0
randomized	0
","	0
open	0
-	0
label	0
","	0
crossover	0
study	0
to	0
receive	0
a	0
single	0
oral	0
dose	0
of	0
desipramine	1
(	0
50	0
mg	0
)	0
on	0
two	0
separate	0
occasions	0
","	0
once	0
alone	0
and	0
once	0
after	0
multiple	0
doses	0
of	0
cinacalcet	1
(	0
90	0
mg	0
for	0
7	0
days	0
)	0
.	0
Blood	0
samples	0
were	0
obtained	0
predose	0
and	0
up	0
to	0
72	0
h	0
postdose	0
.	0
RESULTS	0
:	0
Fourteen	0
subjects	0
completed	0
both	0
treatment	0
arms	0
.	0
Relative	0
to	0
desipramine	1
alone	0
","	0
mean	0
AUC	0
and	0
C	0
(	0
max	0
)	0
of	0
desipramine	1
increased	0
3	0
.	0
6	0
-	0
and	0
1	0
.	0
8	0
-	0
fold	0
when	0
coadministered	0
with	0
cinacalcet	1
.	0
The	0
t	0
(	0
1	0
/	0
2	0
","	0
z	0
)	0
of	0
desipramine	1
was	0
longer	0
when	0
desipramine	1
was	0
coadministered	0
with	0
cinacalcet	1
(	0
21	0
.	0
0	0
versus	0
43	0
.	0
3	0
hs	0
)	0
.	0
The	0
t	0
(	0
max	0
)	0
was	0
similar	0
between	0
the	0
regimens	0
.	0
Fewer	0
subjects	0
reported	0
adverse	0
events	0
following	0
treatment	0
with	0
desipramine	1
alone	0
than	0
when	0
receiving	0
desipramine	1
with	0
cinacalcet	1
(	0
33	0
versus	0
86	0
%	0
)	0
","	0
the	0
most	0
frequent	0
of	0
which	0
(	0
nausea	3
and	0
headache	3
)	0
have	0
been	0
reported	0
for	0
patients	0
treated	0
with	0
either	0
desipramine	1
or	0
cinacalcet	1
.	0
C0NCLUSI0N	0
:	0
This	0
study	0
demonstrates	0
that	0
cinacalcet	1
is	0
a	0
strong	0
inhibitor	0
of	0
CYP2D6	0
.	0
These	0
data	0
suggest	0
that	0
during	0
concomitant	0
treatment	0
with	0
cinacalcet	1
","	0
dose	0
adjustment	0
may	0
be	0
necessary	0
for	0
drugs	0
that	0
demonstrate	0
a	0
narrow	0
therapeutic	0
index	0
and	0
are	0
metabolized	0
by	0
CYP2D6	0
.	0
Case	0
report	0
:	0
acute	0
unintentional	0
carbachol	1
intoxication	0
.	0
INTR0DUCTI0N	0
:	0
Intoxications	0
with	0
carbachol	1
","	0
a	0
muscarinic	0
cholinergic	0
receptor	0
agonist	0
are	0
rare	0
.	0
We	0
report	0
an	0
interesting	0
case	0
investigating	0
a	0
(	0
near	0
)	0
fatal	0
poisoning	3
.	0
METH0DS	0
:	0
The	0
son	0
of	0
an	0
84	0
-	0
year	0
-	0
old	0
male	0
discovered	0
a	0
newspaper	0
report	0
stating	0
clinical	0
success	0
with	0
plant	0
extracts	0
in	0
Alzheimer	3
'	4
s	4
disease	4
.	0
The	0
mode	0
of	0
action	0
was	0
said	0
to	0
be	0
comparable	0
to	0
that	0
of	0
the	0
synthetic	0
compound	0
'	0
carbamylcholin	1
'	0
;	0
that	0
is	0
","	0
carbachol	1
.	0
He	0
bought	0
25	0
g	0
of	0
carbachol	1
as	0
pure	0
substance	0
in	0
a	0
pharmacy	0
","	0
and	0
the	0
father	0
was	0
administered	0
400	0
to	0
500	0
mg	0
.	0
Carbachol	1
concentrations	0
in	0
serum	0
and	0
urine	0
on	0
day	0
1	0
and	0
2	0
of	0
hospital	0
admission	0
were	0
analysed	0
by	0
HPLC	0
-	0
mass	0
spectrometry	0
.	0
RESULTS	0
:	0
Minutes	0
after	0
oral	0
administration	0
","	0
the	0
patient	0
developed	0
nausea	3
","	0
sweating	0
and	0
hypotension	3
","	0
and	0
finally	0
collapsed	0
.	0
Bradycardia	3
","	0
cholinergic	0
symptoms	0
and	0
asystole	3
occurred	0
.	0
Initial	0
cardiopulmonary	0
resuscitation	0
and	0
immediate	0
treatment	0
with	0
adrenaline	1
(	0
epinephrine	1
)	0
","	0
atropine	1
and	0
furosemide	1
was	0
successful	0
.	0
0n	0
hospital	0
admission	0
","	0
blood	0
pressure	0
of	0
the	0
intubated	0
","	0
bradyarrhythmic	0
patient	0
was	0
100	0
/	0
65	0
mmHg	0
.	0
Further	0
signs	0
were	0
hyperhidrosis	3
","	0
hypersalivation	3
","	0
bronchorrhoea	3
","	0
and	0
severe	0
miosis	3
;	0
the	0
electrocardiographic	0
finding	0
was	0
atrio	3
-	4
ventricular	4
dissociation	4
.	0
High	0
doses	0
of	0
atropine	1
(	0
up	0
to	0
50	0
mg	0
per	0
24	0
hours	0
)	0
","	0
adrenaline	1
and	0
dopamine	1
were	0
necessary	0
.	0
The	0
patient	0
was	0
extubated	0
1	0
week	0
later	0
.	0
However	0
","	0
increased	0
dyspnoea	3
and	0
bronchospasm	3
necessitated	0
reintubation	0
.	0
Respiratory	3
insufficiency	4
was	0
further	0
worsened	0
by	0
Proteus	3
mirabilis	4
infection	4
and	0
severe	0
bronchoconstriction	0
.	0
0ne	0
week	0
later	0
","	0
the	0
patient	0
was	0
again	0
extubated	0
and	0
3	0
days	0
later	0
was	0
transferred	0
to	0
a	0
peripheral	0
ward	0
.	0
0n	0
the	0
next	0
day	0
he	0
died	0
","	0
probably	0
as	0
a	0
result	0
of	0
heart	3
failure	4
.	0
Serum	0
samples	0
from	0
the	0
first	0
and	0
second	0
days	0
contained	0
3	0
.	0
6	0
and	0
1	0
.	0
9	0
mg	0
/	0
l	0
carbachol	1
","	0
respectively	0
.	0
The	0
corresponding	0
urine	0
concentrations	0
amounted	0
to	0
374	0
and	0
554	0
mg	0
/	0
l	0
.	0
C0NCLUSI0N	0
:	0
This	0
case	0
started	0
with	0
a	0
media	0
report	0
in	0
a	0
popular	0
newspaper	0
","	0
initiated	0
by	0
published	0
","	0
peer	0
-	0
reviewed	0
research	0
on	0
herbals	0
","	0
and	0
involved	0
human	0
failure	0
in	0
a	0
case	0
history	0
","	0
medical	0
examination	0
and	0
clinical	0
treatment	0
.	0
For	0
the	0
first	0
time	0
","	0
an	0
analytical	0
method	0
for	0
the	0
determination	0
of	0
carbachol	1
in	0
plasma	0
and	0
urine	0
has	0
been	0
developed	0
.	0
The	0
analysed	0
carbachol	1
concentration	0
exceeded	0
the	0
supposed	0
serum	0
level	0
resulting	0
from	0
a	0
therapeutic	0
dose	0
by	0
a	0
factor	0
of	0
130	0
to	0
260	0
.	0
Especially	0
in	0
old	0
patients	0
","	0
intensivists	0
should	0
consider	0
intoxications	0
(	0
with	0
cholinergics	0
)	0
as	0
a	0
cause	0
of	0
acute	3
cardiovascular	4
failure	4
.	0
Pharmacological	0
evidence	0
for	0
the	0
potential	0
of	0
Daucus	0
carota	0
in	0
the	0
management	0
of	0
cognitive	3
dysfunctions	4
.	0
The	0
present	0
study	0
was	0
aimed	0
at	0
investigating	0
the	0
effects	0
of	0
Daucus	0
carota	0
seeds	0
on	0
cognitive	0
functions	0
","	0
total	0
serum	0
cholesterol	1
levels	0
and	0
brain	0
cholinesterase	0
activity	0
in	0
mice	0
.	0
The	0
ethanolic	0
extract	1
of	2
Daucus	2
carota	2
seeds	2
(	0
DCE	1
)	0
was	0
administered	0
orally	0
in	0
three	0
doses	0
(	0
100	0
","	0
200	0
","	0
400	0
mg	0
/	0
kg	0
)	0
for	0
seven	0
successive	0
days	0
to	0
different	0
groups	0
of	0
young	0
and	0
aged	0
mice	0
.	0
Elevated	0
plus	0
maze	0
and	0
passive	0
avoidance	0
apparatus	0
served	0
as	0
the	0
exteroceptive	0
behavioral	0
models	0
for	0
testing	0
memory	0
.	0
Diazepam	1
-	0
","	0
scopolamine	1
-	0
and	0
ageing	0
-	0
induced	0
amnesia	3
served	0
as	0
the	0
interoceptive	0
behavioral	0
models	0
.	0
DCE	1
(	0
200	0
","	0
400	0
mg	0
/	0
kg	0
","	0
p	0
.	0
o	0
.	0
)	0
showed	0
significant	0
improvement	0
in	0
memory	0
scores	0
of	0
young	0
and	0
aged	0
mice	0
.	0
The	0
extent	0
of	0
memory	0
improvement	0
evoked	0
by	0
DCE	1
was	0
23	0
%	0
at	0
the	0
dose	0
of	0
200	0
mg	0
/	0
kg	0
and	0
35	0
%	0
at	0
the	0
dose	0
of	0
400	0
mg	0
/	0
kg	0
in	0
young	0
mice	0
using	0
elevated	0
plus	0
maze	0
.	0
Similarly	0
","	0
significant	0
improvements	0
in	0
memory	0
scores	0
were	0
observed	0
using	0
passive	0
avoidance	0
apparatus	0
and	0
aged	0
mice	0
.	0
Furthermore	0
","	0
DCE	1
reversed	0
the	0
amnesia	3
induced	0
by	0
scopolamine	1
(	0
0	0
.	0
4	0
mg	0
/	0
kg	0
","	0
i	0
.	0
p	0
.	0
)	0
and	0
diazepam	1
(	0
1	0
mg	0
/	0
kg	0
","	0
i	0
.	0
p	0
.	0
)	0
.	0
Daucus	1
carota	2
extract	2
(	0
200	0
","	0
400	0
mg	0
/	0
kg	0
","	0
p	0
.	0
o	0
.	0
)	0
reduced	0
significantly	0
the	0
brain	0
acetylcholinesterase	0
activity	0
and	0
cholesterol	1
levels	0
in	0
young	0
and	0
aged	0
mice	0
.	0
The	0
extent	0
of	0
inhibition	0
of	0
brain	0
cholinesterase	0
activity	0
evoked	0
by	0
DCE	1
at	0
the	0
dose	0
of	0
400	0
mg	0
/	0
kg	0
was	0
22	0
%	0
in	0
young	0
and	0
19	0
%	0
in	0
aged	0
mice	0
.	0
There	0
was	0
a	0
remarkable	0
reduction	0
in	0
total	0
cholesterol	1
level	0
as	0
well	0
","	0
to	0
the	0
extent	0
of	0
23	0
%	0
in	0
young	0
and	0
21	0
%	0
in	0
aged	0
animals	0
with	0
this	0
dose	0
of	0
DCE	1
.	0
Therefore	0
","	0
DCE	1
may	0
prove	0
to	0
be	0
a	0
useful	0
remedy	0
for	0
the	0
management	0
of	0
cognitive	3
dysfunctions	4
on	0
account	0
of	0
its	0
multifarious	0
beneficial	0
effects	0
such	0
as	0
","	0
memory	0
improving	0
property	0
","	0
cholesterol	1
lowering	0
property	0
and	0
anticholinesterase	0
activity	0
.	0
Valproic	1
acid	2
induced	0
encephalopathy	3
-	0
-	0
19	0
new	0
cases	0
in	0
Germany	0
from	0
1994	0
to	0
2003	0
-	0
-	0
a	0
side	0
effect	0
associated	0
to	0
VPA	1
-	0
therapy	0
not	0
only	0
in	0
young	0
children	0
.	0
Valproic	1
acid	2
(	0
VPA	1
)	0
is	0
a	0
broad	0
-	0
spectrum	0
antiepileptic	0
drug	0
and	0
is	0
usually	0
well	0
-	0
tolerated	0
.	0
Rare	0
serious	0
complications	0
may	0
occur	0
in	0
some	0
patients	0
","	0
including	0
haemorrhagic	0
pancreatitis	3
","	0
bone	3
marrow	4
suppression	4
","	0
VPA	1
-	0
induced	0
hepatotoxicity	3
and	0
VPA	1
-	0
induced	0
encephalopathy	3
.	0
The	0
typical	0
signs	0
of	0
VPA	1
-	0
induced	0
encephalopathy	3
are	0
impaired	3
consciousness	4
","	0
sometimes	0
marked	0
EEG	0
background	0
slowing	0
","	0
increased	0
seizure	3
frequency	0
","	0
with	0
or	0
without	0
hyperammonemia	3
.	0
There	0
is	0
still	0
no	0
proof	0
of	0
causative	0
effect	0
of	0
VPA	1
in	0
patients	0
with	0
encephalopathy	3
","	0
but	0
only	0
of	0
an	0
association	0
with	0
an	0
assumed	0
causal	0
relation	0
.	0
We	0
report	0
19	0
patients	0
with	0
VPA	1
-	0
associated	0
encephalopathy	3
in	0
Germany	0
from	0
the	0
years	0
1994	0
to	0
2003	0
","	0
none	0
of	0
whom	0
had	0
been	0
published	0
previously	0
.	0
Cerebral	3
haemorrhage	4
induced	0
by	0
warfarin	1
-	0
the	0
influence	0
of	0
drug	0
-	0
drug	0
interactions	0
.	0
PURP0SE	0
:	0
To	0
evaluate	0
the	0
frequency	0
","	0
severity	0
and	0
preventability	0
of	0
warfarin	1
-	0
induced	0
cerebral	3
haemorrhages	4
due	0
to	0
warfarin	1
and	0
warfarin	1
-	0
drug	0
interactions	0
in	0
patients	0
living	0
in	0
the	0
county	0
of	0
0sterg	0
tland	0
","	0
Sweden	0
.	0
METH0DS	0
:	0
All	0
patients	0
with	0
a	0
diagnosed	0
cerebral	3
haemorrhage	4
at	0
three	0
hospitals	0
during	0
the	0
period	0
2000	0
-	0
2002	0
were	0
identified	0
.	0
Medical	0
records	0
were	0
studied	0
retrospectively	0
to	0
evaluate	0
whether	0
warfarin	1
and	0
warfarin	1
-	0
drug	0
interactions	0
could	0
have	0
caused	0
the	0
cerebral	3
haemorrhage	4
.	0
The	0
proportion	0
of	0
possibly	0
avoidable	0
cases	0
due	0
to	0
drug	0
interactions	0
was	0
estimated	0
.	0
RESULTS	0
:	0
Among	0
593	0
patients	0
with	0
cerebral	3
haemorrhage	4
","	0
59	0
(	0
10	0
%	0
)	0
were	0
assessed	0
as	0
related	0
to	0
warfarin	1
treatment	0
.	0
This	0
imply	0
an	0
incidence	0
of	0
1	0
.	0
7	0
/	0
100	0
","	0
0	0
treatment	0
years	0
.	0
0f	0
the	0
59	0
cases	0
","	0
26	0
(	0
44	0
%	0
)	0
had	0
a	0
fatal	0
outcome	0
","	0
compared	0
to	0
136	0
(	0
25	0
%	0
)	0
among	0
the	0
non	0
-	0
warfarin	1
patients	0
(	0
p	0
<	0
0	0
.	0
1	0
)	0
.	0
A	0
warfarin	1
-	0
drug	0
interaction	0
could	0
have	0
contributed	0
to	0
the	0
haemorrhage	3
in	0
24	0
(	0
41	0
%	0
)	0
of	0
the	0
warfarin	1
patients	0
and	0
in	0
7	0
of	0
these	0
(	0
12	0
%	0
)	0
the	0
bleeding	3
complication	0
was	0
considered	0
being	0
possible	0
to	0
avoid	0
.	0
C0NCLUSI0NS	0
:	0
Warfarin	1
-	0
induced	0
cerebral	3
haemorrhages	4
are	0
a	0
major	0
clinical	0
problem	0
with	0
a	0
high	0
fatality	0
rate	0
.	0
Almost	0
half	0
of	0
the	0
cases	0
was	0
related	0
to	0
a	0
warfarin	1
-	0
drug	0
interaction	0
.	0
A	0
significant	0
proportion	0
of	0
warfarin	1
-	0
related	0
cerebral	3
haemorrhages	4
might	0
have	0
been	0
prevented	0
if	0
greater	0
caution	0
had	0
been	0
taken	0
when	0
prescribing	0
drugs	0
known	0
to	0
interact	0
with	0
warfarin	1
.	0
Antipsychotic	0
-	0
like	0
profile	0
of	0
thioperamide	1
","	0
a	0
selective	0
H3	0
-	0
receptor	0
antagonist	0
in	0
mice	0
.	0
Experimental	0
and	0
clinical	0
evidence	0
points	0
to	0
a	0
role	0
of	0
central	0
histaminergic	0
system	0
in	0
the	0
pathogenesis	0
of	0
schizophrenia	3
.	0
The	0
present	0
study	0
was	0
designed	0
to	0
study	0
the	0
effect	0
of	0
histamine	1
H	0
(	0
3	0
)	0
-	0
receptor	0
ligands	0
on	0
neuroleptic	0
-	0
induced	0
catalepsy	3
","	0
apomorphine	1
-	0
induced	0
climbing	0
behavior	0
and	0
amphetamine	1
-	0
induced	0
locomotor	0
activities	0
in	0
mice	0
.	0
Catalepsy	3
was	0
induced	0
by	0
haloperidol	1
(	0
2	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
)	0
","	0
while	0
apomorphine	1
(	0
1	0
.	0
5	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
and	0
amphetamine	1
(	0
2	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
were	0
used	0
for	0
studying	0
climbing	0
behavior	0
and	0
locomotor	0
activities	0
","	0
respectively	0
.	0
(	1
R	2
)	2
-	2
alpha	2
-	2
methylhistamine	2
(	0
RAMH	1
)	0
(	0
5	0
microg	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
and	0
thioperamide	1
(	0
THP	1
)	0
(	0
15	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
","	0
per	0
se	0
did	0
not	0
cause	0
catalepsy	3
.	0
Administration	0
of	0
THP	1
(	0
3	0
.	0
75	0
","	0
7	0
.	0
5	0
and	0
15	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
1	0
h	0
prior	0
to	0
haloperidol	1
resulted	0
in	0
a	0
dose	0
-	0
dependent	0
increase	0
in	0
the	0
catalepsy	3
times	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
However	0
","	0
pretreatment	0
with	0
RAMH	1
significantly	0
reversed	0
such	0
an	0
effect	0
of	0
THP	1
(	0
15	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
.	0
RAMH	1
per	0
se	0
showed	0
significant	0
reduction	0
in	0
locomotor	0
time	0
","	0
distance	0
traveled	0
and	0
average	0
speed	0
but	0
THP	1
(	0
15	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
per	0
se	0
had	0
no	0
effect	0
on	0
these	0
parameters	0
.	0
0n	0
amphetamine	1
-	0
induced	0
hyperactivity	3
","	0
THP	1
(	0
3	0
.	0
75	0
and	0
7	0
.	0
5	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
reduced	0
locomotor	0
time	0
","	0
distance	0
traveled	0
and	0
average	0
speed	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
Pretreatment	0
with	0
RAMH	1
(	0
5	0
microg	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
could	0
partially	0
reverse	0
such	0
effects	0
of	0
THP	1
(	0
3	0
.	0
75	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
.	0
Climbing	0
behavior	0
induced	0
by	0
apomorphine	1
was	0
reduced	0
in	0
animals	0
treated	0
with	0
THP	1
.	0
Such	0
an	0
effect	0
was	0
","	0
however	0
","	0
reversed	0
in	0
presence	0
of	0
RAMH	1
.	0
THP	1
exhibited	0
an	0
antipsychotic	0
-	0
like	0
profile	0
by	0
potentiating	0
haloperidol	1
-	0
induced	0
catalepsy	3
","	0
reducing	0
amphetamine	1
-	0
induced	0
hyperactivity	3
and	0
reducing	0
apomorphine	1
-	0
induced	0
climbing	0
in	0
mice	0
.	0
Such	0
effects	0
of	0
THP	1
were	0
reversed	0
by	0
RAMH	1
indicating	0
the	0
involvement	0
of	0
histamine	1
H	0
(	0
3	0
)	0
-	0
receptors	0
.	0
Findings	0
suggest	0
a	0
potential	0
for	0
H	0
(	0
3	0
)	0
-	0
receptor	0
antagonists	0
in	0
improving	0
the	0
refractory	0
cases	0
of	0
schizophrenia	3
.	0
Cauda	3
equina	4
syndrome	4
after	0
epidural	0
steroid	1
injection	0
:	0
a	0
case	0
report	0
.	0
0BJECTIVE	0
:	0
Conventional	0
treatment	0
methods	0
of	0
lumbusacral	0
radiculopathy	3
are	0
physical	0
therapy	0
","	0
epidural	0
steroid	1
injections	0
","	0
oral	0
medications	0
","	0
and	0
spinal	0
manipulative	0
therapy	0
.	0
Cauda	3
equina	4
syndrome	4
is	0
a	0
rare	0
complication	0
of	0
epidural	0
anesthesia	0
.	0
The	0
following	0
case	0
is	0
a	0
report	0
of	0
cauda	3
equina	4
syndrome	4
possibly	0
caused	0
by	0
epidural	0
injection	0
of	0
triamcinolone	1
and	0
bupivacaine	1
.	0
CLINICAL	0
FEATURES	0
:	0
A	0
50	0
-	0
year	0
-	0
old	0
woman	0
with	0
low	3
back	4
and	4
right	4
leg	4
pain	4
was	0
scheduled	0
for	0
epidural	0
steroid	1
injection	0
.	0
INTERVENTI0N	0
AND	0
0UTC0ME	0
:	0
An	0
18	0
-	0
gauge	0
Touhy	0
needle	0
was	0
inserted	0
until	0
loss	0
of	0
resistance	0
occurred	0
at	0
the	0
L4	0
-	0
5	0
level	0
.	0
Spread	0
of	0
the	0
contrast	0
medium	0
within	0
the	0
epidural	0
space	0
was	0
determined	0
by	0
radiographic	0
imaging	0
.	0
After	0
verifying	0
the	0
epidural	0
space	0
","	0
bupivacaine	1
and	0
triamcinolone	1
diacetate	2
were	0
injected	0
.	0
After	0
the	0
injection	0
","	0
there	0
was	0
a	0
reduction	0
in	0
radicular	0
symptoms	0
.	0
Three	0
hours	0
later	0
","	0
she	0
complained	0
of	0
perineal	0
numbness	3
and	0
lower	3
extremity	4
weakness	4
.	0
The	0
neurologic	0
evaluation	0
revealed	0
loss	3
of	4
sensation	4
in	0
the	0
saddle	0
area	0
and	0
medial	0
aspect	0
of	0
her	0
right	0
leg	0
.	0
There	0
was	0
a	0
decrease	0
in	0
the	0
perception	0
of	0
pinprick	0
test	0
.	0
Deep	0
-	0
tendon	0
reflexes	0
were	0
decreased	0
especially	0
in	0
the	0
right	0
leg	0
.	0
She	0
was	0
unable	0
to	0
urinate	0
.	0
The	0
patient	0
'	0
s	0
symptoms	0
improved	0
slightly	0
over	0
the	0
next	0
few	0
hours	0
.	0
She	0
had	0
a	0
gradual	0
return	0
of	0
motor	0
function	0
and	0
ability	0
of	0
feeling	0
Foley	0
catheter	0
.	0
All	0
of	0
the	0
symptoms	0
were	0
completely	0
resolved	0
over	0
the	0
next	0
8	0
hours	0
.	0
C0NCLUSI0N	0
:	0
Complications	0
associated	0
with	0
epidural	0
steroid	1
injections	0
are	0
rare	0
.	0
Clinical	0
examination	0
and	0
continued	0
vigilance	0
for	0
neurologic	3
deterioration	4
after	0
epidural	0
steroid	1
injections	0
is	0
important	0
.	0
High	0
-	0
dose	0
testosterone	1
is	0
associated	0
with	0
atherosclerosis	3
in	0
postmenopausal	0
women	0
.	0
0BJECTIVES	0
:	0
To	0
study	0
the	0
long	0
-	0
term	0
effects	0
of	0
androgen	0
treatment	0
on	0
atherosclerosis	3
in	0
postmenopausal	0
women	0
.	0
METH0DS	0
:	0
In	0
a	0
population	0
-	0
based	0
study	0
in	0
513	0
naturally	0
postmenopausal	0
women	0
aged	0
54	0
-	0
67	0
years	0
","	0
we	0
studied	0
the	0
association	0
between	0
self	0
-	0
reported	0
intramuscularly	0
administered	0
high	0
-	0
dose	0
estrogen	1
-	0
testosterone	1
therapy	0
(	0
estradiol	1
-	2
and	2
testosterone	2
esters	2
)	0
and	0
aortic	0
atherosclerosis	3
.	0
Aortic	0
atherosclerosis	3
was	0
diagnosed	0
by	0
radiographic	0
detection	0
of	0
calcified	0
deposits	0
in	0
the	0
abdominal	0
aorta	0
","	0
which	0
have	0
been	0
shown	0
to	0
reflect	0
intima	0
atherosclerosis	3
.	0
Hormone	0
therapy	0
users	0
were	0
compared	0
with	0
never	0
users	0
.	0
RESULTS	0
:	0
Intramuscular	0
hormone	0
therapy	0
use	0
for	0
1	0
year	0
or	0
longer	0
was	0
reported	0
by	0
25	0
women	0
.	0
In	0
almost	0
half	0
of	0
these	0
women	0
severe	0
atherosclerosis	3
of	0
the	0
aorta	0
was	0
present	0
(	0
n	0
=	0
11	0
)	0
","	0
while	0
in	0
women	0
without	0
hormone	0
use	0
severe	0
atherosclerosis	3
of	0
the	0
aorta	0
was	0
present	0
in	0
less	0
than	0
20	0
%	0
(	0
0R	0
3	0
.	0
1	0
;	0
95	0
%	0
CI	0
","	0
1	0
.	0
1	0
-	0
8	0
.	0
5	0
","	0
adjusted	0
for	0
age	0
","	0
years	0
since	0
menopause	0
","	0
smoking	0
","	0
and	0
body	0
mass	0
index	0
)	0
.	0
The	0
association	0
remained	0
after	0
additional	0
adjustment	0
for	0
diabetes	3
","	0
cholesterol	1
level	0
","	0
systolic	0
blood	0
pressure	0
","	0
or	0
alcohol	1
use	0
.	0
No	0
association	0
was	0
found	0
for	0
hormone	0
use	0
less	0
than	0
1	0
year	0
.	0
C0NCLUSI0N	0
:	0
0ur	0
results	0
suggest	0
that	0
high	0
-	0
dose	0
testosterone	1
therapy	0
may	0
adversely	0
affect	0
atherosclerosis	3
in	0
postmenopausal	0
women	0
and	0
indicate	0
that	0
androgen	0
replacement	0
in	0
these	0
women	0
may	0
not	0
be	0
harmless	0
.	0
0ptimising	0
stroke	3
prevention	0
in	0
non	0
-	0
valvular	0
atrial	3
fibrillation	4
.	0
Atrial	3
fibrillation	4
is	0
associated	0
with	0
substantial	0
morbidity	0
and	0
mortality	0
.	0
Pooled	0
data	0
from	0
trials	0
comparing	0
antithrombotic	0
treatment	0
with	0
placebo	0
have	0
shown	0
that	0
warfarin	1
reduces	0
the	0
risk	0
of	0
stroke	3
by	0
62	0
%	0
","	0
and	0
that	0
aspirin	1
alone	0
reduces	0
the	0
risk	0
by	0
22	0
%	0
.	0
0verall	0
","	0
in	0
high	0
-	0
risk	0
patients	0
","	0
warfarin	1
is	0
superior	0
to	0
aspirin	1
in	0
preventing	0
strokes	3
","	0
with	0
a	0
relative	0
risk	0
reduction	0
of	0
36	0
%	0
.	0
Ximelagatran	1
","	0
an	0
oral	0
direct	0
thrombin	0
inhibitor	0
","	0
was	0
found	0
to	0
be	0
as	0
efficient	0
as	0
vitamin	1
K	2
antagonist	0
drugs	0
in	0
the	0
prevention	0
of	0
embolic	3
events	4
","	0
but	0
has	0
been	0
recently	0
withdrawn	0
because	0
of	0
abnormal	3
liver	4
function	4
tests	0
.	0
The	0
ACTIVE	0
-	0
W	0
(	0
Atrial	3
Fibrillation	4
Clopidogrel	1
Trial	0
with	0
Irbesartan	1
for	0
Prevention	0
of	0
Vascular	0
Events	0
)	0
study	0
has	0
demonstrated	0
that	0
warfarin	1
is	0
superior	0
to	0
platelet	0
therapy	0
(	0
clopidogrel	1
plus	0
aspirin	1
)	0
in	0
the	0
prevention	0
af	0
embolic	3
events	4
.	0
Idraparinux	1
","	0
a	0
Factor	0
Xa	0
inhibitor	0
","	0
is	0
being	0
evaluated	0
in	0
patients	0
with	0
atrial	3
fibrillation	4
.	0
Angiotensin	1
-	0
converting	0
enzyme	0
inhibitors	0
and	0
angiotensin	1
II	2
receptor	0
-	0
blocking	0
drugs	0
hold	0
promise	0
in	0
atrial	3
fibrillation	4
through	0
cardiac	3
remodelling	4
.	0
Preliminary	0
studies	0
suggest	0
that	0
statins	1
could	0
interfere	0
with	0
the	0
risk	0
of	0
recurrence	0
after	0
electrical	0
cardioversion	0
.	0
Finally	0
","	0
percutaneous	0
methods	0
for	0
the	0
exclusion	0
of	0
left	0
atrial	0
appendage	0
are	0
under	0
investigation	0
in	0
high	0
-	0
risk	0
patients	0
.	0
Anti	0
-	0
oxidant	0
effects	0
of	0
atorvastatin	1
in	0
dexamethasone	1
-	0
induced	0
hypertension	3
in	0
the	0
rat	0
.	0
1	0
.	0
Dexamethasone	1
(	0
Dex	1
)	0
-	0
induced	0
hypertension	3
is	0
characterized	0
by	0
endothelial	0
dysfunction	0
associated	0
with	0
nitric	1
oxide	2
(	0
N0	1
)	0
deficiency	0
and	0
increased	0
superoxide	1
(	0
02	1
-	2
)	0
production	0
.	0
Atorvastatin	1
(	0
Ato	1
)	0
possesses	0
pleiotropic	0
properties	0
that	0
have	0
been	0
reported	0
to	0
improve	0
endothelial	0
function	0
through	0
increased	0
availability	0
of	0
N0	1
and	0
reduced	0
02	1
-	2
production	0
in	0
various	0
forms	0
of	0
hypertension	3
.	0
In	0
the	0
present	0
study	0
","	0
we	0
investigated	0
whether	0
50	0
mg	0
/	0
kg	0
per	0
day	0
","	0
p	0
.	0
o	0
.	0
","	0
Ato	1
could	0
prevent	0
endothelial	0
N0	1
synthase	0
(	0
eN0S	0
)	0
downregulation	0
and	0
the	0
increase	0
in	0
02	1
-	2
in	0
Sprague	0
-	0
Dawley	0
(	0
SD	0
)	0
rats	0
","	0
thereby	0
reducing	0
blood	0
pressure	0
.	0
2	0
.	0
Male	0
SD	0
rats	0
(	0
n	0
=	0
30	0
)	0
were	0
treated	0
with	0
Ato	1
(	0
50	0
mg	0
/	0
kg	0
per	0
day	0
in	0
drinking	0
water	0
)	0
or	0
tap	0
water	0
for	0
15	0
days	0
.	0
Dexamethasone	1
(	0
10	0
microg	0
/	0
kg	0
per	0
day	0
","	0
s	0
.	0
c	0
.	0
)	0
or	0
saline	0
was	0
started	0
after	0
4	0
days	0
in	0
Ato	1
-	0
treated	0
and	0
non	0
-	0
treated	0
rats	0
and	0
continued	0
for	0
11	0
-	0
13	0
days	0
.	0
Systolic	0
blood	0
pressure	0
(	0
SBP	0
)	0
was	0
measured	0
on	0
alternate	0
days	0
using	0
the	0
tail	0
-	0
cuff	0
method	0
.	0
Endothelial	0
function	0
was	0
assessed	0
by	0
acetylcholine	1
-	0
induced	0
vasorelaxation	0
and	0
phenylephrine	1
-	0
induced	0
vasoconstriction	0
in	0
aortic	0
segments	0
.	0
Vascular	0
eN0S	0
mRNA	0
was	0
assessed	0
by	0
semi	0
-	0
quantitative	0
reverse	0
transcription	0
-	0
polymerase	0
chain	0
reaction	0
.	0
3	0
.	0
In	0
rats	0
treated	0
with	0
Dex	1
alone	0
","	0
SBP	0
was	0
increased	0
from	0
109	0
+	0
/	0
-	0
2	0
to	0
133	0
+	0
/	0
-	0
2	0
mmHg	0
on	0
Days	0
4	0
and	0
Day	0
14	0
","	0
respectively	0
(	0
P	0
<	0
0	0
.	0
1	0
)	0
.	0
In	0
the	0
Ato	1
+	0
Dex	1
group	0
","	0
SBP	0
was	0
increased	0
from	0
113	0
+	0
/	0
-	0
2	0
to	0
119	0
+	0
/	0
-	0
2	0
mmHg	0
on	0
Days	0
4	0
to	0
14	0
","	0
respectively	0
(	0
P	0
<	0
0	0
.	0
1	0
)	0
","	0
but	0
was	0
significantly	0
lower	0
than	0
SBP	0
in	0
the	0
group	0
treated	0
with	0
Dex	1
alone	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
Endothelial	0
-	0
dependent	0
relaxation	0
and	0
eN0S	0
mRNA	0
expression	0
were	0
greater	0
in	0
the	0
Dex	1
+	0
Ato	1
group	0
than	0
in	0
the	0
Dex	1
only	0
group	0
(	0
P	0
<	0
0	0
.	0
5	0
and	0
P	0
<	0
0	0
.	0
1	0
","	0
respectively	0
)	0
.	0
Aortic	0
superoxide	1
production	0
was	0
lower	0
in	0
the	0
Dex	1
+	0
Ato	1
group	0
compared	0
with	0
the	0
group	0
treated	0
with	0
Dex	1
alone	0
(	0
P	0
<	0
0	0
.	0
1	0
)	0
.	0
4	0
.	0
Treatment	0
with	0
Ato	1
improved	0
endothelial	0
function	0
","	0
reduced	0
superoxide	1
production	0
and	0
reduced	0
SBP	0
in	0
Dex	1
-	0
treated	0
SD	0
rats	0
.	0
Severe	0
citrate	1
toxicity	3
complicating	0
volunteer	0
apheresis	0
platelet	0
donation	0
.	0
We	0
report	0
a	0
case	0
of	0
severe	0
citrate	1
toxicity	3
during	0
volunteer	0
donor	0
apheresis	0
platelet	0
collection	0
.	0
The	0
donor	0
was	0
a	0
40	0
-	0
year	0
-	0
old	0
female	0
","	0
first	0
-	0
time	0
apheresis	0
platelet	0
donor	0
.	0
Past	0
medical	0
history	0
was	0
remarkable	0
for	0
hypertension	3
","	0
hyperlipidemia	3
","	0
and	0
depression	3
.	0
Reported	0
medications	0
included	0
bumetanide	1
","	0
pravastatin	1
","	0
and	0
paroxetine	1
.	0
Thirty	0
minutes	0
from	0
the	0
start	0
of	0
the	0
procedure	0
","	0
the	0
donor	0
noted	0
tingling	0
around	0
the	0
mouth	0
","	0
hands	0
","	0
and	0
feet	0
.	0
She	0
then	0
very	0
rapidly	0
developed	0
acute	0
onset	0
of	0
severe	0
facial	0
and	0
extremity	0
tetany	3
.	0
Empirical	0
treatment	0
with	0
intravenous	0
calcium	1
gluconate	2
was	0
initiated	0
","	0
and	0
muscle	3
contractions	4
slowly	0
subsided	0
over	0
approximately	0
10	0
to	0
15	0
minutes	0
.	0
The	0
events	0
are	0
consistent	0
with	0
a	0
severe	0
reaction	0
to	0
calcium	1
chelation	0
by	0
sodium	1
citrate	2
anticoagulant	0
resulting	0
in	0
symptomatic	0
systemic	0
hypocalcemia	3
.	0
Upon	0
additional	0
retrospective	0
analysis	0
","	0
it	0
was	0
noted	0
that	0
bumetanide	1
is	0
a	0
loop	1
diuretic	2
that	0
may	0
cause	0
significant	0
hypocalcemia	3
.	0
We	0
conclude	0
that	0
careful	0
screening	0
for	0
medications	0
and	0
underlying	0
conditions	0
predisposing	0
to	0
hypocalcemia	3
is	0
recommended	0
to	0
help	0
prevent	0
severe	0
reactions	0
due	0
to	0
citrate	1
toxicity	3
.	0
Laboratory	0
measurement	0
of	0
pre	0
-	0
procedure	0
serum	0
calcium	1
levels	0
in	0
selected	0
donors	0
may	0
identify	0
cases	0
requiring	0
heightened	0
vigilance	0
.	0
The	0
case	0
also	0
illustrates	0
the	0
importance	0
of	0
maintaining	0
preparedness	0
for	0
managing	0
rare	0
but	0
serious	0
reactions	0
in	0
volunteer	0
apheresis	0
blood	0
donors	0
.	0
Sirolimus	1
-	0
associated	0
proteinuria	3
and	0
renal	3
dysfunction	4
.	0
Sirolimus	1
is	0
a	0
novel	0
immunosuppressant	0
with	0
potent	0
antiproliferative	0
actions	0
through	0
its	0
ability	0
to	0
inhibit	0
the	0
raptor	0
-	0
containing	0
mammalian	0
target	0
of	0
rapamycin	1
protein	0
kinase	0
.	0
Sirolimus	1
represents	0
a	0
major	0
therapeutic	0
advance	0
in	0
the	0
prevention	0
of	0
acute	0
renal	0
allograft	0
rejection	0
and	0
chronic	0
allograft	0
nephropathy	3
.	0
Its	0
role	0
in	0
the	0
therapy	0
of	0
glomerulonephritis	3
","	0
autoimmunity	3
","	0
cystic	3
renal	4
diseases	4
and	0
renal	3
cancer	4
is	0
under	0
investigation	0
.	0
Because	0
sirolimus	1
does	0
not	0
share	0
the	0
vasomotor	0
renal	0
adverse	0
effects	0
exhibited	0
by	0
calcineurin	0
inhibitors	0
","	0
it	0
has	0
been	0
designated	0
a	0
'	0
non	0
-	0
nephrotoxic	3
drug	0
'	0
.	0
However	0
","	0
clinical	0
reports	0
suggest	0
that	0
","	0
under	0
some	0
circumstances	0
","	0
sirolimus	1
is	0
associated	0
with	0
proteinuria	3
and	0
acute	3
renal	4
dysfunction	4
.	0
A	0
common	0
risk	0
factor	0
appears	0
to	0
be	0
presence	0
of	0
pre	0
-	0
existing	0
chronic	3
renal	4
damage	4
.	0
The	0
mechanisms	0
of	0
sirolimus	1
-	0
associated	0
proteinuria	3
are	0
multifactorial	0
and	0
may	0
be	0
due	0
to	0
an	0
increase	0
in	0
glomerular	0
capillary	0
pressure	0
following	0
calcineurin	0
inhibitor	0
withdrawal	0
.	0
It	0
has	0
also	0
been	0
suggested	0
that	0
sirolimus	1
directly	0
causes	0
increased	0
glomerular	0
permeability	0
/	0
injury	0
","	0
but	0
evidence	0
for	0
this	0
mechanism	0
is	0
currently	0
inconclusive	0
.	0
The	0
acute	3
renal	4
dysfunction	4
associated	0
with	0
sirolimus	1
(	0
such	0
as	0
in	0
delayed	0
graft	0
function	0
)	0
may	0
be	0
due	0
to	0
suppression	0
of	0
compensatory	0
renal	0
cell	0
proliferation	0
and	0
survival	0
/	0
repair	0
processes	0
.	0
Although	0
these	0
adverse	0
effects	0
occur	0
in	0
some	0
patients	0
","	0
their	0
occurrence	0
could	0
be	0
minimised	0
by	0
knowledge	0
of	0
the	0
molecular	0
effects	0
of	0
sirolimus	1
on	0
the	0
kidney	0
","	0
the	0
use	0
of	0
sirolimus	1
in	0
appropriate	0
patient	0
populations	0
","	0
close	0
monitoring	0
of	0
proteinuria	3
and	0
renal	0
function	0
","	0
use	0
of	0
angiotensin	1
-	0
converting	0
enzyme	0
inhibitors	0
or	0
angiotensin	1
II	2
receptor	0
blockers	0
if	0
proteinuria	3
occurs	0
and	0
withdrawal	0
if	0
needed	0
.	0
Further	0
long	0
-	0
term	0
analysis	0
of	0
renal	0
allograft	0
studies	0
using	0
sirolimus	1
as	0
de	0
novo	0
immunosuppression	0
along	0
with	0
clinical	0
and	0
laboratory	0
studies	0
will	0
refine	0
these	0
issues	0
in	0
the	0
future	0
.	0
Proteinuria	3
after	0
conversion	0
to	0
sirolimus	1
in	0
renal	0
transplant	0
recipients	0
.	0
Sirolimus	1
(	0
SRL	1
)	0
is	0
a	0
new	0
","	0
potent	0
immunosuppressive	0
agent	0
.	0
More	0
recently	0
","	0
proteinuria	3
has	0
been	0
reported	0
as	0
a	0
consequence	0
of	0
sirolimus	1
therapy	0
","	0
although	0
the	0
mechanism	0
has	0
remained	0
unclear	0
.	0
We	0
retrospectively	0
examined	0
the	0
records	0
of	0
25	0
renal	0
transplant	0
patients	0
","	0
who	0
developed	0
or	0
displayed	0
increased	0
proteinuria	3
after	0
SRL	1
conversion	0
.	0
The	0
patient	0
cohort	0
(	0
14	0
men	0
","	0
11	0
women	0
)	0
was	0
treated	0
with	0
SRL	1
as	0
conversion	0
therapy	0
","	0
due	0
to	0
chronic	3
allograft	4
nephropathy	4
(	0
CAN	3
)	0
(	0
n	0
=	0
15	0
)	0
neoplasia	3
(	0
n	0
=	0
8	0
)	0
;	0
Kaposi	3
'	4
s	4
sarcoma	4
","	0
Four	0
skin	3
cancers	4
","	0
0ne	0
intestinal	3
tumors	4
","	0
0ne	0
renal	3
cell	4
carsinom	4
)	0
or	0
BK	0
virus	0
nephropathy	3
(	0
n	0
=	0
2	0
)	0
.	0
SRL	1
was	0
started	0
at	0
a	0
mean	0
of	0
78	0
+	0
/	0
-	0
42	0
(	0
15	0
to	0
163	0
)	0
months	0
after	0
transplantation	0
.	0
Mean	0
follow	0
-	0
up	0
on	0
SRL	1
therapy	0
was	0
20	0
+	0
/	0
-	0
12	0
(	0
6	0
to	0
43	0
)	0
months	0
.	0
Proteinuria	3
increased	0
from	0
0	0
.	0
445	0
(	0
0	0
to	0
1	0
.	0
5	0
)	0
g	0
/	0
d	0
before	0
conversion	0
to	0
3	0
.	0
2	0
g	0
/	0
dL	0
(	0
0	0
.	0
2	0
to	0
12	0
)	0
after	0
conversion	0
(	0
P	0
=	0
0	0
.	0
1	0
)	0
.	0
Before	0
conversion	0
8	0
(	0
32	0
%	0
)	0
patients	0
had	0
no	0
proteinuria	3
","	0
whereas	0
afterwards	0
all	0
patients	0
had	0
proteinuria	3
.	0
In	0
28	0
%	0
of	0
patients	0
proteinuria	3
remained	0
unchanged	0
","	0
whereas	0
it	0
increased	0
in	0
68	0
%	0
of	0
patients	0
.	0
In	0
40	0
%	0
it	0
increased	0
by	0
more	0
than	0
100	0
%	0
.	0
Twenty	0
-	0
eight	0
percent	0
of	0
patients	0
showed	0
increased	0
proteinuria	3
to	0
the	0
nephrotic	3
range	0
.	0
Biopsies	0
performed	0
in	0
five	0
patients	0
revealed	0
new	0
pathological	0
changes	0
:	0
0ne	0
membranoproliferative	3
glomerulopathy	4
and	0
interstitial	3
nephritis	4
.	0
These	0
patients	0
showed	0
persistently	0
good	0
graft	0
function	0
.	0
Serum	0
creatinine	1
values	0
did	0
not	0
change	0
significantly	0
:	0
1	0
.	0
98	0
+	0
/	0
-	0
0	0
.	0
8	0
mg	0
/	0
dL	0
before	0
SRL	1
therapy	0
and	0
2	0
.	0
53	0
+	0
/	0
-	0
1	0
.	0
9	0
mg	0
/	0
dL	0
at	0
last	0
follow	0
-	0
up	0
(	0
P	0
=	0
.	0
14	0
)	0
.	0
Five	0
grafts	0
were	0
lost	0
and	0
the	0
patients	0
returned	0
to	0
dialysis	0
.	0
Five	0
patients	0
displayed	0
CAN	3
and	0
Kaposi	3
'	4
s	4
sarcoma	4
.	0
Mean	0
urinary	0
protein	0
of	0
patients	0
who	0
returned	0
to	0
dialysis	0
was	0
1	0
.	0
26	0
(	0
0	0
.	0
5	0
to	0
3	0
.	0
5	0
)	0
g	0
/	0
d	0
before	0
and	0
4	0
.	0
7	0
(	0
3	0
to	0
12	0
)	0
g	0
/	0
d	0
after	0
conversion	0
(	0
P	0
=	0
.	0
1	0
)	0
.	0
Mean	0
serum	0
creatinine	1
level	0
before	0
conversion	0
was	0
2	0
.	0
21	0
mg	0
/	0
dL	0
and	0
thereafter	0
","	0
4	0
.	0
93	0
mg	0
/	0
dL	0
(	0
P	0
=	0
.	0
2	0
)	0
.	0
Heavy	0
proteinuria	3
was	0
common	0
after	0
the	0
use	0
of	0
SRL	1
as	0
rescue	0
therapy	0
for	0
renal	0
transplantation	0
.	0
Therefore	0
","	0
conversion	0
should	0
be	0
considered	0
for	0
patients	0
who	0
have	0
not	0
developed	0
advanced	0
CAN	3
and	0
proteinuria	3
.	0
The	0
possibility	0
of	0
de	0
novo	0
glomerular	0
pathology	0
under	0
SRL	1
treatment	0
requires	0
further	0
investigation	0
by	0
renal	0
biopsy	0
.	0
Long	0
-	0
term	0
follow	0
-	0
up	0
of	0
ifosfamide	1
renal	3
toxicity	4
in	0
children	0
treated	0
for	0
malignant	3
mesenchymal	4
tumors	4
:	0
an	0
International	0
Society	0
of	0
Pediatric	0
0ncology	0
report	0
.	0
The	0
renal	0
function	0
of	0
74	0
children	0
with	0
malignant	3
mesenchymal	4
tumors	4
in	0
complete	0
remission	0
and	0
who	0
have	0
received	0
the	0
same	0
ifosfamide	1
chemotherapy	0
protocol	0
(	0
International	0
Society	0
of	0
Pediatric	0
0ncology	0
Malignant	3
Mesenchymal	4
Tumor	4
Study	0
84	0
[	0
SI0P	0
MMT	0
84	0
]	0
)	0
were	0
studied	0
1	0
year	0
after	0
the	0
completion	0
of	0
treatment	0
.	0
Total	0
cumulative	0
doses	0
were	0
36	0
or	0
60	0
g	0
/	0
m2	0
of	0
ifosfamide	1
(	0
six	0
or	0
10	0
cycles	0
of	0
ifosfamide	1
","	2
vincristine	2
","	2
and	2
dactinomycin	2
[	0
IVA	1
]	0
)	0
.	0
None	0
of	0
them	0
had	0
received	0
cisplatin	1
chemotherapy	0
.	0
Ages	0
ranged	0
from	0
4	0
months	0
to	0
17	0
years	0
;	0
58	0
patients	0
were	0
males	0
and	0
42	0
females	0
.	0
The	0
most	0
common	0
primary	0
tumor	3
site	0
was	0
the	0
head	0
and	0
neck	0
.	0
Renal	0
function	0
was	0
investigated	0
by	0
measuring	0
plasma	0
and	0
urinary	0
electrolytes	0
","	0
glucosuria	3
","	0
proteinuria	3
","	0
aminoaciduria	3
","	0
urinary	0
pH	0
","	0
osmolarity	0
","	0
creatinine	1
clearance	0
","	0
phosphate	1
tubular	0
reabsorption	0
","	0
beta	0
2	0
microglobulinuria	0
","	0
and	0
lysozymuria	0
.	0
Fifty	0
-	0
eight	0
patients	0
(	0
78	0
%	0
)	0
had	0
normal	0
renal	0
tests	0
","	0
whereas	0
16	0
patients	0
(	0
22	0
%	0
)	0
had	0
renal	3
abnormalities	4
.	0
Two	0
subsets	0
of	0
patients	0
were	0
identified	0
from	0
this	0
latter	0
group	0
:	0
the	0
first	0
included	0
four	0
patients	0
(	0
5	0
%	0
of	0
the	0
total	0
population	0
)	0
who	0
developed	0
major	0
toxicity	3
resulting	0
in	0
Fanconi	3
'	4
s	4
syndrome	4
(	0
TDFS	3
)	0
;	0
and	0
the	0
second	0
group	0
included	0
five	0
patients	0
with	0
elevated	0
beta	0
2	0
microglobulinuria	0
and	0
low	0
phosphate	1
reabsorption	0
.	0
The	0
remaining	0
seven	0
patients	0
had	0
isolated	0
beta	0
2	0
microglobulinuria	0
.	0
Severe	0
toxicity	3
was	0
correlated	0
with	0
the	0
higher	0
cumulative	0
dose	0
of	0
60	0
g	0
/	0
m2	0
of	0
ifosfamide	1
","	0
a	0
younger	0
age	0
(	0
less	0
than	0
2	0
1	0
/	0
2	0
years	0
old	0
)	0
","	0
and	0
a	0
predominance	0
of	0
vesicoprostatic	0
tumor	3
involvement	0
.	0
This	0
low	0
percentage	0
(	0
5	0
%	0
)	0
of	0
TDFS	0
must	0
be	0
evaluated	0
with	0
respect	0
to	0
the	0
efficacy	0
of	0
ifosfamide	1
in	0
the	0
treatment	0
of	0
mesenchymal	3
tumors	4
in	0
children	0
.	0
Progressive	0
myopathy	3
with	0
up	0
-	0
regulation	0
of	0
MHC	0
-	0
I	0
associated	0
with	0
statin	1
therapy	0
.	0
Statins	1
can	0
cause	0
a	0
necrotizing	0
myopathy	3
and	0
hyperCKaemia	3
which	0
is	0
reversible	0
on	0
cessation	0
of	0
the	0
drug	0
.	0
What	0
is	0
less	0
well	0
known	0
is	0
a	0
phenomenon	0
whereby	0
statins	1
may	0
induce	0
a	0
myopathy	3
","	0
which	0
persists	0
or	0
may	0
progress	0
after	0
stopping	0
the	0
drug	0
.	0
We	0
investigated	0
the	0
muscle	0
pathology	0
in	0
8	0
such	0
cases	0
.	0
All	0
had	0
myofibre	0
necrosis	3
but	0
only	0
3	0
had	0
an	0
inflammatory	0
infiltrate	0
.	0
In	0
all	0
cases	0
there	0
was	0
diffuse	0
or	0
multifocal	0
up	0
-	0
regulation	0
of	0
MHC	0
-	0
I	0
expression	0
even	0
in	0
non	0
-	0
necrotic	3
fibres	0
.	0
Progressive	0
improvement	0
occurred	0
in	0
7	0
cases	0
after	0
commencement	0
of	0
prednisolone	1
and	0
methotrexate	1
","	0
and	0
in	0
one	0
case	0
spontaneously	0
.	0
These	0
observations	0
suggest	0
that	0
statins	1
may	0
initiate	0
an	0
immune	0
-	0
mediated	0
myopathy	3
that	0
persists	0
after	0
withdrawal	0
of	0
the	0
drug	0
and	0
responds	0
to	0
immunosuppressive	0
therapy	0
.	0
The	0
mechanism	0
of	0
this	0
myopathy	3
is	0
uncertain	0
but	0
may	0
involve	0
the	0
induction	0
by	0
statins	1
of	0
an	0
endoplasmic	0
reticulum	0
stress	0
response	0
with	0
associated	0
up	0
-	0
regulation	0
of	0
MHC	0
-	0
I	0
expression	0
and	0
antigen	0
presentation	0
by	0
muscle	0
fibres	0
.	0
Use	0
of	0
chromosome	0
substitution	0
strains	0
to	0
identify	0
seizure	3
susceptibility	0
loci	0
in	0
mice	0
.	0
Seizure	3
susceptibility	0
varies	0
among	0
inbred	0
mouse	0
strains	0
.	0
Chromosome	0
substitution	0
strains	0
(	0
CSS	0
)	0
","	0
in	0
which	0
a	0
single	0
chromosome	0
from	0
one	0
inbred	0
strain	0
(	0
donor	0
)	0
has	0
been	0
transferred	0
onto	0
a	0
second	0
strain	0
(	0
host	0
)	0
by	0
repeated	0
backcrossing	0
","	0
may	0
be	0
used	0
to	0
identify	0
quantitative	0
trait	0
loci	0
(	0
QTLs	0
)	0
that	0
contribute	0
to	0
seizure	3
susceptibility	0
.	0
QTLs	0
for	0
susceptibility	0
to	0
pilocarpine	1
-	0
induced	0
seizures	3
","	0
a	0
model	0
of	0
temporal	3
lobe	4
epilepsy	4
","	0
have	0
not	0
been	0
reported	0
","	0
and	0
CSS	0
have	0
not	0
previously	0
been	0
used	0
to	0
localize	0
seizure	3
susceptibility	0
genes	0
.	0
We	0
report	0
QTLs	0
identified	0
using	0
a	0
B6	0
(	0
host	0
)	0
x	0
A	0
/	0
J	0
(	0
donor	0
)	0
CSS	0
panel	0
to	0
localize	0
genes	0
involved	0
in	0
susceptibility	0
to	0
pilocarpine	1
-	0
induced	0
seizures	3
.	0
Three	0
hundred	0
fifty	0
-	0
five	0
adult	0
male	0
CSS	0
mice	0
","	0
58	0
B6	0
","	0
and	0
39	0
A	0
/	0
J	0
were	0
tested	0
for	0
susceptibility	0
to	0
pilocarpine	1
-	0
induced	0
seizures	3
.	0
Highest	0
stage	0
reached	0
and	0
latency	0
to	0
each	0
stage	0
were	0
recorded	0
for	0
all	0
mice	0
.	0
B6	0
mice	0
were	0
resistant	0
to	0
seizures	3
and	0
slower	0
to	0
reach	0
stages	0
compared	0
to	0
A	0
/	0
J	0
mice	0
.	0
The	0
CSS	0
for	0
Chromosomes	0
10	0
and	0
18	0
progressed	0
to	0
the	0
most	0
severe	0
stages	0
","	0
diverging	0
dramatically	0
from	0
the	0
B6	0
phenotype	0
.	0
Latencies	0
to	0
stages	0
were	0
also	0
significantly	0
shorter	0
for	0
CSS10	0
and	0
CSS18	0
mice	0
.	0
CSS	0
mapping	0
suggests	0
seizure	3
susceptibility	0
loci	0
on	0
mouse	0
Chromosomes	0
10	0
and	0
18	0
.	0
This	0
approach	0
provides	0
a	0
framework	0
for	0
identifying	0
potentially	0
novel	0
homologous	0
candidate	0
genes	0
for	0
human	0
temporal	3
lobe	4
epilepsy	4
.	0
In	0
vitro	0
characterization	0
of	0
parasympathetic	0
and	0
sympathetic	0
responses	0
in	0
cyclophosphamide	1
-	0
induced	0
cystitis	3
in	0
the	0
rat	0
.	0
In	0
cyclophosphamide	1
-	0
induced	0
cystitis	3
in	0
the	0
rat	0
","	0
detrusor	0
function	0
is	0
impaired	0
and	0
the	0
expression	0
and	0
effects	0
of	0
muscarinic	0
receptors	0
altered	0
.	0
Whether	0
or	0
not	0
the	0
neuronal	0
transmission	0
may	0
be	0
affected	0
by	0
cystitis	3
was	0
presently	0
investigated	0
.	0
Responses	0
of	0
urinary	0
strip	0
preparations	0
from	0
control	0
and	0
cyclophosphamide	1
-	0
pretreated	0
rats	0
to	0
electrical	0
field	0
stimulation	0
and	0
to	0
agonists	0
were	0
assessed	0
in	0
the	0
absence	0
and	0
presence	0
of	0
muscarinic	0
","	0
adrenergic	0
and	0
purinergic	0
receptor	0
antagonists	0
.	0
Generally	0
","	0
atropine	1
reduced	0
contractions	0
","	0
but	0
in	0
contrast	0
to	0
controls	0
","	0
it	0
also	0
reduced	0
responses	0
to	0
low	0
electrical	0
field	0
stimulation	0
intensity	0
(	0
1	0
-	0
5	0
Hz	0
)	0
in	0
inflamed	0
preparations	0
.	0
In	0
both	0
types	0
","	0
purinoceptor	0
desensitization	0
with	0
alpha	1
","	2
beta	2
-	2
methylene	2
adenosine	2
-	2
5	2
'	2
-	2
triphosphate	2
(	0
alpha	1
","	2
beta	2
-	2
meATP	2
)	0
caused	0
further	0
reductions	0
at	0
low	0
frequencies	0
(	0
<	0
10	0
Hz	0
)	0
.	0
The	0
muscarinic	0
receptor	0
antagonists	0
atropine	1
","	0
4	1
-	2
diphenylacetoxy	2
-	2
N	2
-	2
methylpiperidine	2
(	0
4	1
-	2
DAMP	2
)	0
(	0
'	0
M	0
(	0
1	0
)	0
/	0
M	0
(	0
3	0
)	0
/	0
M	0
(	0
5	0
)	0
-	0
selective	0
'	0
)	0
","	0
methoctramine	1
(	0
'	0
M	0
(	0
2	0
)	0
-	0
selective	0
'	0
)	0
and	0
pirenzepine	1
(	0
'	0
M	0
(	0
1	0
)	0
-	0
selective	0
'	0
)	0
antagonized	0
the	0
tonic	0
component	0
of	0
the	0
electrical	0
field	0
stimulation	0
-	0
evoked	0
contractile	0
response	0
more	0
potently	0
than	0
the	0
phasic	0
component	0
.	0
4	1
-	2
DAMP	2
inhibited	0
the	0
tonic	0
contractions	0
in	0
controls	0
more	0
potently	0
than	0
methoctramine	1
and	0
pirenzepine	1
.	0
In	0
inflamed	0
preparations	0
","	0
the	0
muscarinic	0
receptor	0
antagonism	0
on	0
the	0
phasic	0
component	0
of	0
the	0
electrical	0
field	0
stimulation	0
-	0
evoked	0
contraction	0
was	0
decreased	0
and	0
the	0
pirenzepine	1
and	0
4	1
-	2
DAMP	2
antagonism	0
on	0
the	0
tonic	0
component	0
was	0
much	0
less	0
efficient	0
than	0
in	0
controls	0
.	0
In	0
contrast	0
to	0
controls	0
","	0
methoctramine	1
increased	0
-	0
-	0
instead	0
of	0
decreased	0
-	0
-	0
the	0
tonic	0
responses	0
at	0
high	0
frequencies	0
.	0
While	0
contractions	0
to	0
carbachol	1
and	0
ATP	1
were	0
the	0
same	0
in	0
inflamed	0
and	0
in	0
control	0
strips	0
when	0
related	0
to	0
a	0
reference	0
potassium	1
response	0
","	0
isoprenaline	1
-	0
induced	0
relaxations	0
were	0
smaller	0
in	0
inflamed	0
strips	0
.	0
Thus	0
","	0
in	0
cystitis	3
substantial	0
changes	0
of	0
the	0
efferent	0
functional	0
responses	0
occur	0
.	0
While	0
postjunctional	0
beta	0
-	0
adrenoceptor	0
-	0
mediated	0
relaxations	0
are	0
reduced	0
","	0
effects	0
by	0
prejunctional	0
inhibitory	0
muscarinic	0
receptors	0
may	0
be	0
increased	0
.	0
Direct	0
inhibition	0
of	0
cardiac	0
hyperpolarization	0
-	0
activated	0
cyclic	1
nucleotide	2
-	0
gated	0
pacemaker	0
channels	0
by	0
clonidine	1
.	0
BACKGR0UND	0
:	0
Inhibition	0
of	0
cardiac	0
sympathetic	0
tone	0
represents	0
an	0
important	0
strategy	0
for	0
treatment	0
of	0
cardiovascular	3
disease	4
","	0
including	0
arrhythmia	3
","	0
coronary	3
heart	4
disease	4
","	0
and	0
chronic	0
heart	3
failure	4
.	0
Activation	0
of	0
presynaptic	0
alpha2	0
-	0
adrenoceptors	0
is	0
the	0
most	0
widely	0
accepted	0
mechanism	0
of	0
action	0
of	0
the	0
antisympathetic	0
drug	0
clonidine	1
;	0
however	0
","	0
other	0
target	0
proteins	0
have	0
been	0
postulated	0
to	0
contribute	0
to	0
the	0
in	0
vivo	0
actions	0
of	0
clonidine	1
.	0
METH0DS	0
AND	0
RESULTS	0
:	0
To	0
test	0
whether	0
clonidine	1
elicits	0
pharmacological	0
effects	0
independent	0
of	0
alpha2	0
-	0
adrenoceptors	0
","	0
we	0
have	0
generated	0
mice	0
with	0
a	0
targeted	0
deletion	0
of	0
all	0
3	0
alpha2	0
-	0
adrenoceptor	0
subtypes	0
(	0
alpha2ABC	0
-	0
/	0
-	0
)	0
.	0
Alpha2ABC	0
-	0
/	0
-	0
mice	0
were	0
completely	0
unresponsive	0
to	0
the	0
analgesic	0
and	0
hypnotic	0
effects	0
of	0
clonidine	1
;	0
however	0
","	0
clonidine	1
significantly	0
lowered	0
heart	0
rate	0
in	0
alpha2ABC	0
-	0
/	0
-	0
mice	0
by	0
up	0
to	0
150	0
bpm	0
.	0
Clonidine	1
-	0
induced	0
bradycardia	3
in	0
conscious	0
alpha2ABC	0
-	0
/	0
-	0
mice	0
was	0
32	0
.	0
3	0
%	0
(	0
10	0
microg	0
/	0
kg	0
)	0
and	0
26	0
.	0
6	0
%	0
(	0
100	0
microg	0
/	0
kg	0
)	0
of	0
the	0
effect	0
in	0
wild	0
-	0
type	0
mice	0
.	0
A	0
similar	0
bradycardic	0
effect	0
of	0
clonidine	1
was	0
observed	0
in	0
isolated	0
spontaneously	0
beating	0
right	0
atria	0
from	0
alpha2ABC	0
-	0
knockout	0
and	0
wild	0
-	0
type	0
mice	0
.	0
Clonidine	1
inhibited	0
the	0
native	0
pacemaker	0
current	0
(	0
I	0
(	0
f	0
)	0
)	0
in	0
isolated	0
sinoatrial	0
node	0
pacemaker	0
cells	0
and	0
the	0
I	0
(	0
f	0
)	0
-	0
generating	0
hyperpolarization	0
-	0
activated	0
cyclic	1
nucleotide	2
-	0
gated	0
(	0
HCN	0
)	0
2	0
and	0
HCN4	0
channels	0
in	0
transfected	0
HEK293	0
cells	0
.	0
As	0
a	0
consequence	0
of	0
blocking	0
I	0
(	0
f	0
)	0
","	0
clonidine	1
reduced	0
the	0
slope	0
of	0
the	0
diastolic	0
depolarization	0
and	0
the	0
frequency	0
of	0
pacemaker	0
potentials	0
in	0
sinoatrial	0
node	0
cells	0
from	0
wild	0
-	0
type	0
and	0
alpha2ABC	0
-	0
knockout	0
mice	0
.	0
C0NCLUSI0NS	0
:	0
Direct	0
inhibition	0
of	0
cardiac	0
HCN	0
pacemaker	0
channels	0
contributes	0
to	0
the	0
bradycardic	0
effects	0
of	0
clonidine	1
gene	0
-	0
targeted	0
mice	0
in	0
vivo	0
","	0
and	0
thus	0
","	0
clonidine	1
-	0
like	0
drugs	0
represent	0
novel	0
structures	0
for	0
future	0
HCN	0
channel	0
inhibitors	0
.	0
Granulomatous	3
hepatitis	4
due	0
to	0
combination	1
of	2
amoxicillin	2
and	2
clavulanic	2
acid	2
.	0
We	0
report	0
the	0
case	0
of	0
a	0
patient	0
with	0
amoxicillin	1
-	2
clavulanic	2
acid	2
-	0
induced	0
hepatitis	3
with	0
histologic	0
multiple	0
granulomas	3
.	0
This	0
type	0
of	0
lesion	0
broadens	0
the	0
spectrum	0
of	0
liver	3
injury	4
due	0
to	0
this	0
drug	0
combination	0
","	0
mainly	0
represented	0
by	0
a	0
benign	0
cholestatic	3
syndrome	4
.	0
The	0
association	0
of	0
granulomas	3
and	0
eosinophilia	3
favor	0
an	0
immunoallergic	0
mechanism	0
.	0
As	0
penicillin	1
derivatives	0
and	0
amoxicillin	1
alone	0
are	0
known	0
to	0
induce	0
such	0
types	0
of	0
lesions	0
","	0
the	0
amoxicillin	1
component	0
","	0
with	0
or	0
without	0
a	0
potentiating	0
effect	0
of	0
clavulanic	1
acid	2
","	0
might	0
have	0
a	0
major	0
role	0
.	0
Dobutamine	1
stress	0
echocardiography	0
:	0
a	0
sensitive	0
indicator	0
of	0
diminished	0
myocardial	0
function	0
in	0
asymptomatic	0
doxorubicin	1
-	0
treated	0
long	0
-	0
term	0
survivors	0
of	0
childhood	0
cancer	3
.	0
Doxorubicin	1
is	0
an	0
effective	0
anticancer	0
chemotherapeutic	0
agent	0
known	0
to	0
cause	0
acute	0
and	0
chronic	0
cardiomyopathy	3
.	0
To	0
develop	0
a	0
more	0
sensitive	0
echocardiographic	0
screening	0
test	0
for	0
cardiac	3
damage	4
due	0
to	0
doxorubicin	1
","	0
a	0
cohort	0
study	0
was	0
performed	0
using	0
dobutamine	1
infusion	0
to	0
differentiate	0
asymptomatic	0
long	0
-	0
term	0
survivors	0
of	0
childhood	0
cancer	3
treated	0
with	0
doxorubicin	1
from	0
healthy	0
control	0
subjects	0
.	0
Echocardiographic	0
data	0
from	0
the	0
experimental	0
group	0
of	0
21	0
patients	0
(	0
mean	0
age	0
16	0
+	0
/	0
-	0
5	0
years	0
)	0
treated	0
from	0
1	0
.	0
6	0
to	0
14	0
.	0
3	0
years	0
(	0
median	0
5	0
.	0
3	0
)	0
before	0
this	0
study	0
with	0
27	0
to	0
532	0
mg	0
/	0
m2	0
of	0
doxorubicin	1
(	0
mean	0
196	0
)	0
were	0
compared	0
with	0
echocardiographic	0
data	0
from	0
12	0
normal	0
age	0
-	0
matched	0
control	0
subjects	0
.	0
Graded	0
dobutamine	1
infusions	0
of	0
0	0
.	0
5	0
","	0
2	0
.	0
5	0
","	0
5	0
and	0
10	0
micrograms	0
/	0
kg	0
per	0
min	0
were	0
administered	0
.	0
Echocardiographic	0
Doppler	0
studies	0
were	0
performed	0
before	0
infusion	0
and	0
after	0
15	0
min	0
of	0
infusion	0
at	0
each	0
rate	0
.	0
Dobutamine	1
infusion	0
at	0
10	0
micrograms	0
/	0
kg	0
per	0
min	0
was	0
discontinued	0
after	0
six	0
studies	0
secondary	0
to	0
a	0
50	0
%	0
incidence	0
rate	0
of	0
adverse	0
symptoms	0
.	0
The	0
most	0
important	0
findings	0
were	0
that	0
compared	0
with	0
values	0
in	0
control	0
subjects	0
","	0
end	0
-	0
systolic	0
left	0
ventricular	0
posterior	0
wall	0
dimension	0
and	0
percent	0
of	0
left	0
ventricular	0
posterior	0
wall	0
thickening	0
in	0
doxorubicin	1
-	0
treated	0
patients	0
were	0
decreased	0
at	0
baseline	0
study	0
and	0
these	0
findings	0
were	0
more	0
clearly	0
delineated	0
with	0
dobutamine	1
stimulation	0
.	0
End	0
-	0
systolic	0
left	0
ventricular	0
posterior	0
wall	0
dimension	0
at	0
baseline	0
for	0
the	0
doxorubicin	1
-	0
treated	0
group	0
was	0
11	0
+	0
/	0
-	0
1	0
.	0
9	0
mm	0
versus	0
13	0
.	0
1	0
+	0
/	0
-	0
1	0
.	0
5	0
mm	0
for	0
control	0
subjects	0
(	0
p	0
less	0
than	0
0	0
.	0
1	0
)	0
.	0
End	0
-	0
systolic	0
left	0
ventricular	0
posterior	0
wall	0
dimension	0
at	0
the	0
5	0
-	0
micrograms	0
/	0
kg	0
per	0
min	0
dobutamine	1
infusion	0
for	0
the	0
doxorubicin	1
-	0
treated	0
group	0
was	0
14	0
.	0
1	0
+	0
/	0
-	0
2	0
.	0
4	0
mm	0
versus	0
19	0
.	0
3	0
+	0
/	0
-	0
2	0
.	0
6	0
mm	0
for	0
control	0
subjects	0
(	0
p	0
less	0
than	0
0	0
.	0
1	0
)	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0
Influence	0
of	0
smoking	1
on	0
developing	0
cochlea	0
.	0
Does	0
smoking	1
during	0
pregnancy	0
affect	0
the	0
amplitudes	0
of	0
transient	0
evoked	0
otoacoustic	0
emissions	0
in	0
newborns	0
?	0
0BJECTIVE	0
:	0
Maternal	0
tobacco	0
smoking	1
has	0
negative	0
effects	0
on	0
fetal	0
growth	0
.	0
The	0
influence	0
of	0
smoking	1
during	0
pregnancy	0
on	0
the	0
developing	0
cochlea	0
has	0
not	0
been	0
estimated	0
","	0
although	0
smoking	1
has	0
been	0
positively	0
associated	0
with	0
hearing	3
loss	4
in	0
adults	0
.	0
The	0
objective	0
of	0
this	0
study	0
was	0
to	0
determine	0
the	0
effects	0
of	0
maternal	0
smoking	1
on	0
transient	0
evoked	0
otoacoustic	0
emissions	0
(	0
TE0AEs	0
)	0
of	0
healthy	0
neonates	0
.	0
METH0DS	0
:	0
This	0
study	0
was	0
undertaken	0
as	0
part	0
of	0
neonatal	0
screening	0
for	0
hearing	3
impairment	4
and	0
involved	0
both	0
ears	0
of	0
200	0
newborns	0
.	0
Newborns	0
whose	0
mothers	0
reported	0
smoking	1
during	0
pregnancy	0
(	0
n	0
=	0
200	0
ears	0
)	0
were	0
compared	0
to	0
a	0
control	0
group	0
of	0
newborns	0
(	0
n	0
=	0
200	0
ears	0
)	0
","	0
whose	0
mothers	0
were	0
non	0
-	0
smokers	0
.	0
Exposure	0
to	0
tobacco	0
was	0
characterized	0
as	0
low	0
(	0
<	0
5	0
cigarettes	0
per	0
day	0
","	0
n	0
=	0
88	0
ears	0
)	0
","	0
moderate	0
(	0
5	0
<	0
or	0
=	0
cigarettes	0
per	0
day	0
<	0
10	0
","	0
n	0
=	0
76	0
)	0
or	0
high	0
(	0
>	0
or	0
=	0
10	0
cigarettes	0
per	0
day	0
","	0
n	0
=	0
36	0
)	0
.	0
RESULTS	0
:	0
In	0
exposed	0
neonates	0
","	0
TE0AEs	0
mean	0
response	0
(	0
across	0
frequency	0
)	0
and	0
mean	0
amplitude	0
at	0
4000Hz	0
was	0
significantly	0
lower	0
than	0
in	0
non	0
-	0
exposed	0
neonates	0
.	0
Comparisons	0
between	0
exposed	0
newborns	0
'	0
subgroups	0
revealed	0
no	0
significant	0
differences	0
.	0
However	0
","	0
by	0
comparing	0
each	0
subgroup	0
to	0
control	0
group	0
","	0
we	0
found	0
statistically	0
significant	0
decreases	3
of	4
TE0AEs	4
amplitudes	4
at	0
4000Hz	0
for	0
all	0
three	0
groups	0
.	0
Mean	0
TE0AEs	0
responses	0
of	0
highly	0
exposed	0
newborns	0
were	0
also	0
significantly	0
lower	0
in	0
comparison	0
to	0
our	0
control	0
group	0
.	0
C0NCLUSI0N	0
:	0
In	0
utero	0
","	0
exposure	0
to	0
tobacco	0
smoking	1
seems	0
to	0
have	0
a	0
small	0
impact	0
on	0
outer	0
hair	0
cells	0
.	0
These	0
effects	0
seem	0
to	0
be	0
equally	0
TRUE	0
for	0
all	0
exposed	0
newborns	0
","	0
regardless	0
of	0
the	0
degree	0
of	0
exposure	0
.	0
Further	0
studies	0
are	0
needed	0
in	0
order	0
to	0
establish	0
a	0
potential	0
negative	0
effect	0
of	0
maternal	0
smoking	1
on	0
the	0
neonate	0
'	0
s	0
hearing	0
acuity	0
.	0
Simvastatin	1
-	0
induced	0
bilateral	0
leg	0
compartment	3
syndrome	4
and	0
myonecrosis	3
associated	0
with	0
hypothyroidism	3
.	0
A	0
54	0
-	0
year	0
-	0
old	0
hypothyroid	3
male	0
taking	0
thyroxine	1
and	0
simvastatin	1
presented	0
with	0
bilateral	0
leg	0
compartment	3
syndrome	4
and	0
myonecrosis	3
.	0
Urgent	0
fasciotomies	0
were	0
performed	0
and	0
the	0
patient	0
made	0
an	0
uneventful	0
recovery	0
with	0
the	0
withdrawal	0
of	0
simvastatin	1
.	0
It	0
is	0
likely	0
that	0
this	0
complication	0
will	0
be	0
seen	0
more	0
often	0
with	0
the	0
increased	0
worldwide	0
use	0
of	0
this	0
drug	0
and	0
its	0
approval	0
for	0
all	0
arteriopathic	3
patients	0
.	0
Neuroinflammation	3
and	0
behavioral	3
abnormalities	4
after	0
neonatal	0
terbutaline	1
treatment	0
in	0
rats	0
:	0
implications	0
for	0
autism	3
.	0
Autism	3
is	0
a	0
neurodevelopmental	3
disorder	4
presenting	0
before	0
3	0
years	0
of	0
age	0
with	0
deficits	3
in	4
communication	4
and	4
social	4
skills	4
and	0
repetitive	3
behaviors	4
.	0
In	0
addition	0
to	0
genetic	0
influences	0
","	0
recent	0
studies	0
suggest	0
that	0
prenatal	0
drug	0
or	0
chemical	0
exposures	0
are	0
risk	0
factors	0
for	0
autism	3
.	0
Terbutaline	1
","	0
a	0
beta2	0
-	0
adrenoceptor	0
agonist	0
used	0
to	0
arrest	0
preterm	3
labor	4
","	0
has	0
been	0
associated	0
with	0
increased	0
concordance	0
for	0
autism	3
in	0
dizygotic	0
twins	0
.	0
We	0
studied	0
the	0
effects	0
of	0
terbutaline	1
on	0
microglial	0
activation	0
in	0
different	0
brain	0
regions	0
and	0
behavioral	0
outcomes	0
in	0
developing	0
rats	0
.	0
Newborn	0
rats	0
were	0
given	0
terbutaline	1
(	0
10	0
mg	0
/	0
kg	0
)	0
daily	0
on	0
postnatal	0
days	0
(	0
PN	0
)	0
2	0
to	0
5	0
or	0
PN	0
11	0
to	0
14	0
and	0
examined	0
24	0
h	0
after	0
the	0
last	0
dose	0
and	0
at	0
PN	0
30	0
.	0
Immunohistochemical	0
studies	0
showed	0
that	0
administration	0
of	0
terbutaline	1
on	0
PN	0
2	0
to	0
5	0
produced	0
a	0
robust	0
increase	0
in	0
microglial	0
activation	0
on	0
PN	0
30	0
in	0
the	0
cerebral	0
cortex	0
","	0
as	0
well	0
as	0
in	0
cerebellar	0
and	0
cerebrocortical	0
white	0
matter	0
.	0
None	0
of	0
these	0
effects	0
occurred	0
in	0
animals	0
given	0
terbutaline	1
on	0
PN	0
11	0
to	0
14	0
.	0
In	0
behavioral	0
tests	0
","	0
animals	0
treated	0
with	0
terbutaline	1
on	0
PN	0
2	0
to	0
5	0
showed	0
consistent	0
patterns	0
of	0
hyper	0
-	0
reactivity	0
to	0
novelty	0
and	0
aversive	0
stimuli	0
when	0
assessed	0
in	0
a	0
novel	0
open	0
field	0
","	0
as	0
well	0
as	0
in	0
the	0
acoustic	0
startle	0
response	0
test	0
.	0
0ur	0
findings	0
indicate	0
that	0
beta2	0
-	0
adrenoceptor	0
overstimulation	0
during	0
an	0
early	0
critical	0
period	0
results	0
in	0
microglial	0
activation	0
associated	0
with	0
innate	0
neuroinflammatory	0
pathways	0
and	0
behavioral	3
abnormalities	4
","	0
similar	0
to	0
those	0
described	0
in	0
autism	3
.	0
This	0
study	0
provides	0
a	0
useful	0
animal	0
model	0
for	0
understanding	0
the	0
neuropathological	0
processes	0
underlying	0
autism	3
spectrum	4
disorders	4
.	0
Upregulation	0
of	0
brain	0
expression	0
of	0
P	0
-	0
glycoprotein	0
in	0
MRP2	0
-	0
deficient	0
TR	0
(	0
-	0
)	0
rats	0
resembles	0
seizure	3
-	0
induced	0
up	0
-	0
regulation	0
of	0
this	0
drug	0
efflux	0
transporter	0
in	0
normal	0
rats	0
.	0
PURP0SE	0
:	0
The	0
multidrug	0
resistance	0
protein	0
2	0
(	0
MRP2	0
)	0
is	0
a	0
drug	0
efflux	0
transporter	0
that	0
is	0
expressed	0
predominantly	0
at	0
the	0
apical	0
domain	0
of	0
hepatocytes	0
but	0
seems	0
also	0
to	0
be	0
expressed	0
at	0
the	0
apical	0
membrane	0
of	0
brain	0
capillary	0
endothelial	0
cells	0
that	0
form	0
the	0
blood	0
-	0
brain	0
barrier	0
(	0
BBB	0
)	0
.	0
MRP2	0
is	0
absent	0
in	0
the	0
transport	0
-	0
deficient	0
(	0
TR	0
(	0
-	0
)	0
)	0
Wistar	0
rat	0
mutant	0
","	0
so	0
that	0
this	0
rat	0
strain	0
was	0
very	0
helpful	0
in	0
defining	0
substrates	0
of	0
MRP2	0
by	0
comparing	0
tissue	0
concentrations	0
or	0
functional	0
activities	0
of	0
compounds	0
in	0
MRP2	0
-	0
deficient	0
rats	0
with	0
those	0
in	0
transport	0
-	0
competent	0
Wistar	0
rats	0
.	0
By	0
using	0
this	0
strategy	0
to	0
study	0
the	0
involvement	0
of	0
MRP2	0
in	0
brain	0
access	0
of	0
antiepileptic	0
drugs	0
(	0
AEDs	0
)	0
","	0
we	0
recently	0
reported	0
that	0
phenytoin	1
is	0
a	0
substrate	0
for	0
MRP2	0
in	0
the	0
BBB	0
.	0
However	0
","	0
one	0
drawback	0
of	0
such	0
studies	0
in	0
genetically	0
deficient	0
rats	0
is	0
the	0
fact	0
that	0
compensatory	0
changes	0
with	0
upregulation	0
of	0
other	0
transporters	0
can	0
occur	0
.	0
This	0
prompted	0
us	0
to	0
study	0
the	0
brain	0
expression	0
of	0
P	0
-	0
glycoprotein	0
(	0
Pgp	0
)	0
","	0
a	0
major	0
drug	0
efflux	0
transporter	0
in	0
many	0
tissues	0
","	0
including	0
the	0
BBB	0
","	0
in	0
TR	0
(	0
-	0
)	0
rats	0
compared	0
with	0
nonmutant	0
(	0
wild	0
-	0
type	0
)	0
Wistar	0
rats	0
.	0
METH0DS	0
:	0
The	0
expression	0
of	0
MRP2	0
and	0
Pgp	0
in	0
brain	0
and	0
liver	0
sections	0
of	0
TR	0
(	0
-	0
)	0
rats	0
and	0
normal	0
Wistar	0
rats	0
was	0
determined	0
with	0
immunohistochemistry	0
","	0
by	0
using	0
a	0
novel	0
","	0
highly	0
selective	0
monoclonal	0
MRP2	0
antibody	0
and	0
the	0
monoclonal	0
Pgp	0
antibody	0
C219	0
","	0
respectively	0
.	0
RESULTS	0
:	0
Immunofluorescence	0
staining	0
with	0
the	0
MRP2	0
antibody	0
was	0
found	0
to	0
label	0
a	0
high	0
number	0
of	0
microvessels	0
throughout	0
the	0
brain	0
in	0
normal	0
Wistar	0
rats	0
","	0
whereas	0
such	0
labeling	0
was	0
absent	0
in	0
TR	0
(	0
-	0
)	0
rats	0
.	0
TR	0
(	0
-	0
)	0
rats	0
exhibited	0
a	0
significant	0
up	0
-	0
regulation	0
of	0
Pgp	0
in	0
brain	0
capillary	0
endothelial	0
cells	0
compared	0
with	0
wild	0
-	0
type	0
controls	0
.	0
No	0
such	0
obvious	0
upregulation	0
of	0
Pgp	0
was	0
observed	0
in	0
liver	0
sections	0
.	0
A	0
comparable	0
overexpression	0
of	0
Pgp	0
in	0
the	0
BBB	0
was	0
obtained	0
after	0
pilocarpine	1
-	0
induced	0
seizures	3
in	0
wild	0
-	0
type	0
Wistar	0
rats	0
.	0
Experiments	0
with	0
systemic	0
administration	0
of	0
the	0
Pgp	0
substrate	0
phenobarbital	1
and	0
the	0
selective	0
Pgp	0
inhibitor	0
tariquidar	1
in	0
TR	0
(	0
-	0
)	0
rats	0
substantiated	0
that	0
Pgp	0
is	0
functional	0
and	0
compensates	0
for	0
the	0
lack	0
of	0
MRP2	0
in	0
the	0
BBB	0
.	0
C0NCLUSI0NS	0
:	0
The	0
data	0
on	0
TR	0
(	0
-	0
)	0
rats	0
indicate	0
that	0
Pgp	0
plays	0
an	0
important	0
role	0
in	0
the	0
compensation	0
of	0
MRP2	0
deficiency	0
in	0
the	0
BBB	0
.	0
Because	0
such	0
a	0
compensatory	0
mechanism	0
most	0
likely	0
occurs	0
to	0
reduce	0
injury	3
to	4
the	4
brain	4
from	0
cytotoxic	0
compounds	0
","	0
the	0
present	0
data	0
substantiate	0
the	0
concept	0
that	0
MRP2	0
performs	0
a	0
protective	0
role	0
in	0
the	0
BBB	0
.	0
Furthermore	0
","	0
our	0
data	0
suggest	0
that	0
TR	0
(	0
-	0
)	0
rats	0
are	0
an	0
interesting	0
tool	0
to	0
study	0
consequences	0
of	0
overexpression	0
of	0
Pgp	0
in	0
the	0
BBB	0
on	0
access	0
of	0
drugs	0
in	0
the	0
brain	0
","	0
without	0
the	0
need	0
of	0
inducing	0
seizures	3
or	0
other	0
Pgp	0
-	0
enhancing	0
events	0
for	0
this	0
purpose	0
.	0
Role	0
of	0
xanthine	1
oxidase	0
in	0
dexamethasone	1
-	0
induced	0
hypertension	3
in	0
rats	0
.	0
1	0
.	0
Glucocorticoid	0
-	0
induced	0
hypertension	3
(	0
GC	0
-	0
HT	3
)	0
in	0
the	0
rat	0
is	0
associated	0
with	0
nitric	1
oxide	2
-	0
redox	0
imbalance	0
.	0
2	0
.	0
We	0
studied	0
the	0
role	0
of	0
xanthine	1
oxidase	0
(	0
X0	0
)	0
","	0
which	0
is	0
implicated	0
in	0
the	0
production	0
of	0
reactive	0
oxygen	0
species	0
","	0
in	0
dexamethasone	1
-	0
induced	0
hypertension	3
(	0
dex	1
-	0
HT	3
)	0
.	0
3	0
.	0
Thirty	0
male	0
Sprague	0
-	0
Dawley	0
rats	0
were	0
divided	0
randomly	0
into	0
four	0
treatment	0
groups	0
:	0
saline	0
","	0
dexamethasone	1
(	0
dex	1
)	0
","	0
allopurinol	1
plus	0
saline	0
","	0
and	0
allopurinol	1
plus	0
dex	1
.	0
4	0
.	0
Systolic	0
blood	0
pressures	0
(	0
SBP	0
)	0
and	0
bodyweights	0
were	0
recorded	0
each	0
alternate	0
day	0
.	0
Thymus	0
weight	0
was	0
used	0
as	0
a	0
marker	0
of	0
glucocorticoid	0
activity	0
","	0
and	0
serum	0
urate	1
to	0
assess	0
X0	0
inhibition	0
.	0
5	0
.	0
Dex	1
increased	3
SBP	4
(	0
110	0
+	0
/	0
-	0
2	0
-	0
126	0
+	0
/	0
-	0
3	0
mmHg	0
;	0
P	0
<	0
0	0
.	0
1	0
)	0
and	0
decreased	3
thymus	4
(	4
P	4
<	4
0	4
.	4
1	4
)	4
and	4
bodyweights	4
(	0
P	0
cholesteryl	1
ester	2
accumulation	0
following	0
ritonavir	1
treatment	0
.	0
Acute	0
hepatitis	3
attack	0
after	0
exposure	0
to	0
telithromycin	1
.	0
INTR0DUCTI0N	0
:	0
Antibiotic	0
-	0
associated	0
hepatotoxicity	3
is	0
rare	0
.	0
With	0
widespread	0
use	0
of	0
antimicrobial	0
agents	0
","	0
however	0
","	0
hepatic	3
injury	4
occurs	0
frequently	0
","	0
and	0
among	0
adverse	3
drug	4
reactions	4
","	0
idiosyncratic	0
reactions	0
are	0
the	0
most	0
serious	0
.	0
CASE	0
SUMMARY	0
:	0
A	0
25	0
-	0
year	0
-	0
old	0
male	0
patient	0
","	0
with	0
a	0
height	0
of	0
175	0
cm	0
and	0
weight	0
of	0
72	0
kg	0
presented	0
to	0
Marmara	0
University	0
Hospital	0
Emergency	0
Department	0
","	0
Istanbul	0
","	0
Turkey	0
","	0
with	0
5	0
days	0
'	0
history	0
of	0
jaundice	3
","	0
malaise	0
","	0
nausea	3
","	0
and	0
vomiting	3
.	0
He	0
had	0
been	0
prescribed	0
telithromycin	1
400	0
mg	0
/	0
d	0
P0	0
to	0
treat	0
an	0
upper	3
respiratory	4
tract	4
infection	4
7	0
days	0
prior	0
.	0
Admission	0
laboratory	0
tests	0
were	0
as	0
follows	0
:	0
alanine	1
aminotransferase	0
","	0
67	0
U	0
/	0
L	0
(	0
reference	0
range	0
","	0
10	0
-	0
37	0
U	0
/	0
L	0
)	0
;	0
aspartate	1
aminotransferase	0
","	0
98	0
U	0
/	0
L	0
(	0
10	0
-	0
40	0
U	0
/	0
L	0
)	0
;	0
alkaline	0
phosphatase	0
","	0
513	0
U	0
/	0
L	0
(	0
0	0
-	0
270	0
U	0
/	0
L	0
)	0
;	0
gamma	0
-	0
glutamyltransferase	0
","	0
32	0
U	0
/	0
L	0
(	0
7	0
-	0
49	0
U	0
/	0
L	0
)	0
;	0
amylase	0
","	0
46	0
U	0
/	0
L	0
(	0
0	0
-	0
220	0
U	0
/	0
L	0
)	0
;	0
total	0
bilirubin	1
","	0
20	0
.	0
1	0
mg	0
/	0
dL	0
(	0
0	0
.	0
2	0
-	0
1	0
.	0
0	0
mg	0
/	0
dL	0
)	0
;	0
direct	0
bilirubin	1
","	0
14	0
.	0
8	0
mg	0
/	0
dL	0
(	0
0	0
-	0
0	0
.	0
3	0
mg	0
/	0
dL	0
)	0
;	0
and	0
albumin	0
","	0
4	0
.	0
7	0
mg	0
/	0
dL	0
(	0
3	0
.	0
5	0
-	0
5	0
.	0
4	0
mg	0
/	0
dL	0
)	0
.	0
No	0
toxin	0
","	0
alcohol	1
","	0
or	0
other	0
drugs	0
were	0
reported	0
.	0
The	0
patient	0
had	0
suffered	0
a	0
previous	0
episode	0
of	0
"	0
acute	0
hepatitis	3
of	0
unknown	0
origin	0
,	0
"	0
that	0
occurred	0
after	0
telithromycin	1
usage	0
.	0
Both	0
incidents	0
occurred	0
within	0
a	0
year	0
.	0
DISCUSSI0N	0
:	0
Telithromycin	1
is	0
the	0
first	0
of	0
the	0
ketolide	0
antibacterials	0
to	0
receive	0
US	0
Food	0
and	0
Drug	0
Administration	0
approval	0
for	0
clinical	0
use	0
.	0
It	0
has	0
been	0
associated	0
with	0
infrequent	0
and	0
usually	0
reversible	0
severe	0
hepatic	3
dysfunction	4
.	0
Based	0
on	0
a	0
score	0
of	0
8	0
on	0
the	0
Naranjo	0
adverse	3
drug	4
reaction	4
probability	0
scale	0
","	0
telithromycin	1
was	0
the	0
probable	0
cause	0
of	0
acute	0
hepatitis	3
in	0
this	0
patient	0
","	0
and	0
pathological	0
findings	0
suggested	0
drug	0
-	0
induced	0
toxic	3
hepatitis	4
.	0
Recurrence	0
of	0
hepatitis	3
attack	0
might	0
have	0
been	0
avoided	0
if	0
the	0
initial	0
incident	0
had	0
been	0
communicated	0
to	0
the	0
attending	0
physician	0
who	0
prescribed	0
telithromycin	1
the	0
second	0
time	0
.	0
C0NCLUSI0N	0
:	0
Here	0
we	0
report	0
a	0
case	0
of	0
acute	0
hepatitis	3
probably	0
associated	0
with	0
the	0
administration	0
of	0
telithromycin	1
.	0
A	0
study	0
on	0
the	0
effect	0
of	0
the	0
duration	0
of	0
subcutaneous	0
heparin	1
injection	0
on	0
bruising	3
and	0
pain	3
.	0
AIM	0
:	0
This	0
study	0
was	0
carried	0
out	0
to	0
determine	0
the	0
effect	0
of	0
injection	0
duration	0
on	0
bruising	3
and	0
pain	3
following	0
the	0
administration	0
of	0
the	0
subcutaneous	0
injection	0
of	0
heparin	1
.	0
BACKGR0UND	0
:	0
Although	0
different	0
methods	0
to	0
prevent	0
bruising	3
and	0
pain	3
following	0
the	0
subcutaneous	0
injection	0
of	0
heparin	1
have	0
been	0
widely	0
studied	0
and	0
described	0
","	0
the	0
effect	0
of	0
injection	0
duration	0
on	0
the	0
occurrence	0
of	0
bruising	3
and	0
pain	3
is	0
little	0
documented	0
.	0
DESIGN	0
:	0
This	0
study	0
was	0
designed	0
as	0
within	0
-	0
subject	0
","	0
quasi	0
-	0
experimental	0
research	0
.	0
METH0D	0
:	0
The	0
sample	0
for	0
the	0
study	0
consisted	0
of	0
50	0
patients	0
to	0
whom	0
subcutaneous	0
heparin	1
was	0
administered	0
.	0
Heparin	1
was	0
injected	0
over	0
10	0
seconds	0
on	0
the	0
right	0
abdominal	0
site	0
and	0
30	0
seconds	0
on	0
the	0
left	0
abdominal	0
site	0
.	0
Injections	0
areas	0
were	0
assessed	0
for	0
the	0
presence	0
of	0
bruising	3
at	0
48	0
and	0
72	0
hours	0
after	0
each	0
injection	0
.	0
Dimensions	0
of	0
the	0
bruising	3
on	0
the	0
heparin	1
applied	0
areas	0
were	0
measured	0
using	0
transparent	0
millimetric	0
measuring	0
paper	0
.	0
The	0
visual	0
analog	0
scale	0
(	0
VAS	0
)	0
was	0
used	0
to	0
measure	0
pain	3
intensity	0
and	0
a	0
stop	0
-	0
watch	0
was	0
used	0
to	0
time	0
the	0
pain	3
period	0
.	0
Data	0
were	0
analysed	0
using	0
chi	0
-	0
square	0
test	0
","	0
Mann	0
-	0
Whitney	0
U	0
","	0
Wilcoxon	0
signed	0
ranks	0
tests	0
and	0
correlation	0
.	0
RESULTS	0
:	0
The	0
percentage	0
of	0
bruising	3
occurrence	0
was	0
64	0
%	0
with	0
the	0
injection	0
of	0
10	0
seconds	0
duration	0
and	0
42	0
%	0
in	0
the	0
30	0
-	0
second	0
injection	0
.	0
It	0
was	0
determined	0
that	0
the	0
size	0
of	0
the	0
bruising	3
was	0
smaller	0
in	0
the	0
30	0
-	0
second	0
injection	0
.	0
Pain	3
intensity	0
and	0
pain	3
period	0
were	0
statistically	0
significantly	0
lower	0
for	0
the	0
30	0
-	0
second	0
injection	0
than	0
for	0
the	0
10	0
-	0
second	0
injection	0
.	0
C0NCLUSI0NS	0
:	0
It	0
was	0
determined	0
that	0
injection	0
duration	0
had	0
an	0
effect	0
on	0
bruising	3
and	0
pain	3
following	0
the	0
subcutaneous	0
administration	0
of	0
heparin	1
.	0
This	0
study	0
should	0
be	0
repeated	0
on	0
a	0
larger	0
sample	0
.	0
RELEVANCE	0
T0	0
CLINICAL	0
PRACTICE	0
:	0
When	0
administering	0
subcutaneous	0
heparin	1
injections	0
","	0
it	0
is	0
important	0
to	0
extend	0
the	0
duration	0
of	0
the	0
injection	0
.	0
Acute	3
liver	4
failure	4
in	0
two	0
patients	0
with	0
regular	0
alcohol	1
consumption	0
ingesting	0
paracetamol	1
at	0
therapeutic	0
dosage	0
.	0
BACKGR0UND	0
:	0
The	0
possible	0
role	0
of	0
alcohol	1
in	0
the	0
development	0
of	0
hepatotoxicity	3
associated	0
with	0
therapeutic	0
doses	0
of	0
paracetamol	1
(	0
acetaminophen	1
)	0
is	0
currently	0
debated	0
.	0
CASE	0
REP0RT	0
:	0
We	0
describe	0
2	0
patients	0
who	0
were	0
regular	0
consumers	0
of	0
alcohol	1
and	0
who	0
developed	0
liver	3
failure	4
within	0
3	0
-	0
5	0
days	0
after	0
hospitalization	0
and	0
stopping	0
alcohol	1
consumption	0
while	0
being	0
treated	0
with	0
4	0
g	0
paracetamol	1
/	0
day	0
.	0
A	0
paracetamol	1
serum	0
level	0
obtained	0
in	0
one	0
of	0
these	0
patients	0
was	0
not	0
in	0
the	0
toxic	0
range	0
.	0
Possible	0
risk	0
factors	0
for	0
the	0
development	0
of	0
hepatotoxicity	3
in	0
patients	0
treated	0
with	0
therapeutic	0
doses	0
of	0
paracetamol	1
are	0
discussed	0
.	0
C0NCLUSI0N	0
:	0
In	0
patients	0
with	0
risk	0
factors	0
","	0
e	0
.	0
g	0
.	0
regular	0
consumption	0
of	0
alcohol	1
","	0
liver	3
failure	4
is	0
possible	0
when	0
therapeutic	0
doses	0
are	0
ingested	0
.	0
We	0
propose	0
that	0
the	0
paracetamol	1
dose	0
should	0
not	0
exceed	0
2	0
g	0
/	0
day	0
in	0
such	0
patients	0
and	0
that	0
their	0
liver	0
function	0
should	0
be	0
monitored	0
closely	0
while	0
being	0
treated	0
with	0
paracetamol	1
.	0
Associations	0
between	0
use	0
of	0
benzodiazepines	1
or	0
related	0
drugs	0
and	0
health	0
","	0
physical	0
abilities	0
and	0
cognitive	0
function	0
:	0
a	0
non	0
-	0
randomised	0
clinical	0
study	0
in	0
the	0
elderly	0
.	0
0BJECTIVE	0
:	0
To	0
describe	0
associations	0
between	0
the	0
use	0
of	0
benzodiazepines	1
or	0
related	0
drugs	0
(	0
BZDs	1
/	0
RDs	0
)	0
and	0
health	0
","	0
functional	0
abilities	0
and	0
cognitive	0
function	0
in	0
the	0
elderly	0
.	0
METH0DS	0
:	0
A	0
non	0
-	0
randomised	0
clinical	0
study	0
of	0
patients	0
aged	0
>	0
or	0
=	0
65	0
years	0
admitted	0
to	0
acute	0
hospital	0
wards	0
during	0
1	0
month	0
.	0
164	0
patients	0
(	0
mean	0
age	0
+	0
/	0
-	0
standard	0
deviation	0
[	0
SD	0
]	0
81	0
.	0
6	0
+	0
/	0
-	0
6	0
.	0
8	0
years	0
)	0
were	0
admitted	0
.	0
0f	0
these	0
","	0
nearly	0
half	0
(	0
n	0
=	0
78	0
)	0
had	0
used	0
BZDs	1
/	0
RDs	0
before	0
admission	0
","	0
and	0
the	0
remainder	0
(	0
n	0
=	0
86	0
)	0
were	0
non	0
-	0
users	0
.	0
Cognitive	0
ability	0
was	0
assessed	0
by	0
the	0
Mini	0
-	0
Mental	0
State	0
Examination	0
(	0
MMSE	0
)	0
.	0
Patients	0
scoring	0
>	0
or	0
=	0
20	0
MMSE	0
sum	0
points	0
were	0
interviewed	0
(	0
n	0
=	0
79	0
)	0
and	0
questioned	0
regarding	0
symptoms	0
and	0
functional	0
abilities	0
during	0
the	0
week	0
prior	0
to	0
admission	0
.	0
Data	0
on	0
use	0
of	0
BZDs	1
/	0
RDs	0
before	0
admission	0
","	0
current	0
medications	0
and	0
discharge	0
diagnoses	0
were	0
collected	0
from	0
medical	0
records	0
.	0
Health	0
","	0
physical	0
abilities	0
and	0
cognitive	0
function	0
were	0
compared	0
between	0
BZD	0
/	0
RD	0
users	0
and	0
non	0
-	0
users	0
","	0
and	0
adjustments	0
were	0
made	0
for	0
confounding	0
variables	0
.	0
The	0
residual	0
serum	0
concentrations	0
of	0
oxazepam	1
","	0
temazepam	1
and	0
zopiclone	1
were	0
analysed	0
.	0
RESULTS	0
:	0
The	0
mean	0
+	0
/	0
-	0
SD	0
duration	0
of	0
BZD	0
/	0
RD	0
use	0
was	0
7	0
+	0
/	0
-	0
7	0
years	0
(	0
range	0
1	0
-	0
31	0
)	0
.	0
Two	0
or	0
three	0
BZDs	1
/	0
RDs	0
were	0
concomitantly	0
taken	0
by	0
26	0
%	0
of	0
users	0
(	0
n	0
=	0
20	0
)	0
.	0
Long	0
-	0
term	0
use	0
of	0
these	0
drugs	0
was	0
associated	0
with	0
female	0
sex	0
and	0
use	0
of	0
a	0
higher	0
number	0
of	0
drugs	0
with	0
effects	0
on	0
the	0
CNS	0
","	0
which	0
tended	0
to	0
be	0
related	0
to	0
diagnosed	0
dementia	3
.	0
After	0
adjustment	0
for	0
these	0
variables	0
as	0
confounders	0
","	0
use	0
of	0
BZDs	1
/	0
RDs	0
was	0
not	0
associated	0
with	0
cognitive	0
function	0
as	0
measured	0
by	0
the	0
MMSE	0
.	0
However	0
","	0
use	0
of	0
BZDs	1
/	0
RDs	0
was	0
associated	0
with	0
dizziness	3
","	0
inability	3
to	4
sleep	4
after	0
awaking	0
at	0
night	0
and	0
tiredness	3
in	0
the	0
mornings	0
during	0
the	0
week	0
prior	0
to	0
admission	0
and	0
with	0
stronger	0
depressive	3
symptoms	4
measured	0
at	0
the	0
beginning	0
of	0
the	0
hospital	0
stay	0
.	0
Use	0
of	0
BZDs	1
/	0
RDs	0
tended	0
to	0
be	0
associated	0
with	0
a	0
reduced	0
ability	0
to	0
walk	0
and	0
shorter	0
night	0
-	0
time	0
sleep	0
during	0
the	0
week	0
prior	0
to	0
admission	0
.	0
A	0
higher	0
residual	0
serum	0
concentration	0
of	0
temazepam	1
correlated	0
with	0
a	0
lower	0
MMSE	0
sum	0
score	0
after	0
adjustment	0
for	0
confounding	0
variables	0
.	0
C0NCLUSI0NS	0
:	0
Long	0
-	0
term	0
use	0
and	0
concomitant	0
use	0
of	0
more	0
than	0
one	0
BZD	0
/	0
RD	0
were	0
common	0
in	0
elderly	0
patients	0
hospitalised	0
because	0
of	0
acute	0
illnesses	0
.	0
Long	0
-	0
term	0
use	0
was	0
associated	0
with	0
daytime	0
and	0
night	0
-	0
time	0
symptoms	0
indicative	0
of	0
poorer	0
health	0
and	0
potentially	0
caused	0
by	0
the	0
adverse	0
effects	0
of	0
these	0
drugs	0
.	0
Acute	0
vocal	3
fold	4
palsy	4
after	0
acute	0
disulfiram	1
intoxication	0
.	0
Acute	0
peripheral	3
neuropathy	4
caused	0
by	0
a	0
disulfiram	1
overdose	3
is	0
very	0
rare	0
and	0
there	0
is	0
no	0
report	0
of	0
it	0
leading	0
to	0
vocal	3
fold	4
palsy	4
.	0
A	0
49	0
-	0
year	0
-	0
old	0
woman	0
was	0
transferred	0
to	0
our	0
department	0
because	0
of	0
quadriparesis	3
","	0
lancinating	0
pain	3
","	0
sensory	3
loss	4
","	0
and	0
paresthesia	3
of	0
the	0
distal	0
limbs	0
.	0
0ne	0
month	0
previously	0
","	0
she	0
had	0
taken	0
a	0
single	0
high	0
dose	0
of	0
disulfiram	1
(	0
130	0
tablets	0
of	0
ALC0H0L	1
ST0P	0
TAB	0
","	0
Shin	0
-	0
Poong	0
Pharm	0
.	0
Co	0
.	0
","	0
Ansan	0
","	0
Korea	0
)	0
in	0
a	0
suicide	0
attempt	0
.	0
She	0
was	0
not	0
an	0
alcoholic	0
.	0
For	0
the	0
first	0
few	0
days	0
after	0
ingestion	0
","	0
she	0
was	0
in	0
a	0
confused	0
state	0
and	0
had	0
mild	0
to	0
moderate	0
ataxia	3
and	0
giddiness	3
.	0
She	0
noticed	0
hoarseness	3
and	0
distally	0
accentuated	0
motor	0
and	0
sensory	0
dysfunction	0
after	0
she	0
had	0
recovered	0
from	0
this	0
state	0
.	0
A	0
nerve	0
conduction	0
study	0
was	0
consistent	0
with	0
severe	0
sensorimotor	0
axonal	0
polyneuropathy	3
.	0
Laryngeal	0
electromyography	0
(	0
thyroarytenoid	0
muscle	0
)	0
showed	0
ample	0
denervation	0
potentials	0
.	0
Laryngoscopy	0
revealed	0
asymmetric	0
vocal	0
fold	0
movements	0
during	0
phonation	0
.	0
Her	0
vocal	0
change	0
and	0
weakness	0
began	0
to	0
improve	0
spontaneously	0
about	0
3	0
weeks	0
after	0
transfer	0
.	0
This	0
was	0
a	0
case	0
of	0
acute	0
palsy	3
of	0
the	0
recurrent	0
laryngeal	0
nerve	0
and	0
superimposed	0
severe	0
acute	0
sensorimotor	0
axonal	0
polyneuropathy	3
caused	0
by	0
high	0
-	0
dose	0
disulfiram	1
intoxication	0
.	0
Encephalopathy	3
induced	0
by	0
levetiracetam	1
added	0
to	0
valproate	1
.	0
BACKGR0UND	0
:	0
We	0
report	0
on	0
the	0
manifestation	0
of	0
a	0
levetiracetam	1
(	0
LEV	1
)	0
-	0
induced	0
encephalopathy	3
.	0
FINDINGS	0
:	0
A	0
28	0
-	0
year	0
-	0
old	0
man	0
suffering	0
from	0
idiopathic	3
epilepsy	4
with	0
generalized	0
seizures	3
was	0
treated	0
with	0
LEV	1
(	0
3000	0
mg	0
)	0
added	0
to	0
valproate	1
(	0
VPA	1
)	0
(	0
2000	0
mg	0
)	0
.	0
Frequency	0
of	0
generalized	0
tonic	3
-	4
clonic	4
seizures	4
increased	0
from	0
one	0
per	0
6	0
months	0
to	0
two	0
per	0
month	0
.	0
Neuropsychological	0
testing	0
showed	0
impaired	3
word	4
fluency	4
","	4
psychomotor	4
speed	4
and	4
working	4
memory	4
.	0
The	0
interictal	0
electroencephalogram	0
(	0
EEG	0
)	0
showed	0
a	0
generalized	0
slowing	0
to	0
5	0
per	0
second	0
theta	0
rhythms	0
with	0
bilateral	0
generalized	0
high	0
-	0
amplitude	0
discharges	0
.	0
0UTC0ME	0
:	0
Following	0
discontinuation	0
of	0
LEV	1
","	0
EEG	0
and	0
neuropsychological	0
findings	0
improved	0
and	0
seizure	3
frequency	0
decreased	0
.	0
Norepinephrine	1
signaling	0
through	0
beta	0
-	0
adrenergic	0
receptors	0
is	0
critical	0
for	0
expression	0
of	0
cocaine	1
-	0
induced	0
anxiety	3
.	0
BACKGR0UND	0
:	0
Cocaine	1
is	0
a	0
widely	0
abused	0
psychostimulant	0
that	0
has	0
both	0
rewarding	0
and	0
aversive	0
properties	0
.	0
While	0
the	0
mechanisms	0
underlying	0
cocaine	1
'	0
s	0
rewarding	0
effects	0
have	0
been	0
studied	0
extensively	0
","	0
less	0
attention	0
has	0
been	0
paid	0
to	0
the	0
unpleasant	0
behavioral	0
states	0
induced	0
by	0
cocaine	1
","	0
such	0
as	0
anxiety	3
.	0
METH0DS	0
:	0
In	0
this	0
study	0
","	0
we	0
evaluated	0
the	0
performance	0
of	0
dopamine	1
beta	0
-	0
hydroxylase	0
knockout	0
(	0
Dbh	0
-	0
/	0
-	0
)	0
mice	0
","	0
which	0
lack	0
norepinephrine	1
(	0
NE	1
)	0
","	0
in	0
the	0
elevated	0
plus	0
maze	0
(	0
EPM	0
)	0
to	0
examine	0
the	0
contribution	0
of	0
noradrenergic	0
signaling	0
to	0
cocaine	1
-	0
induced	0
anxiety	3
.	0
RESULTS	0
:	0
We	0
found	0
that	0
cocaine	1
dose	0
-	0
dependently	0
increased	0
anxiety	3
-	0
like	0
behavior	0
in	0
control	0
(	0
Dbh	0
+	0
/	0
-	0
)	0
mice	0
","	0
as	0
measured	0
by	0
a	0
decrease	0
in	0
open	0
arm	0
exploration	0
.	0
The	0
Dbh	0
-	0
/	0
-	0
mice	0
had	0
normal	0
baseline	0
performance	0
in	0
the	0
EPM	0
but	0
were	0
completely	0
resistant	0
to	0
the	0
anxiogenic	0
effects	0
of	0
cocaine	1
.	0
Cocaine	1
-	0
induced	0
anxiety	3
was	0
also	0
attenuated	0
in	0
Dbh	0
+	0
/	0
-	0
mice	0
following	0
administration	0
of	0
disulfiram	1
","	0
a	0
dopamine	1
beta	0
-	0
hydroxylase	0
(	0
DBH	0
)	0
inhibitor	0
.	0
In	0
experiments	0
using	0
specific	0
adrenergic	0
antagonists	0
","	0
we	0
found	0
that	0
pretreatment	0
with	0
the	0
beta	0
-	0
adrenergic	0
receptor	0
antagonist	0
propranolol	1
blocked	0
cocaine	1
-	0
induced	0
anxiety	3
-	0
like	0
behavior	0
in	0
Dbh	0
+	0
/	0
-	0
and	0
wild	0
-	0
type	0
C57BL6	0
/	0
J	0
mice	0
","	0
while	0
the	0
alpha	0
(	0
1	0
)	0
antagonist	0
prazosin	1
and	0
the	0
alpha	0
(	0
2	0
)	0
antagonist	0
yohimbine	1
had	0
no	0
effect	0
.	0
C0NCLUSI0NS	0
:	0
These	0
results	0
indicate	0
that	0
noradrenergic	0
signaling	0
via	0
beta	0
-	0
adrenergic	0
receptors	0
is	0
required	0
for	0
cocaine	1
-	0
induced	0
anxiety	3
in	0
mice	0
.	0
Hypothalamic	0
prolactin	0
receptor	0
messenger	0
ribonucleic	1
acid	2
levels	0
","	0
prolactin	0
signaling	0
","	0
and	0
hyperprolactinemic	3
inhibition	0
of	0
pulsatile	0
luteinizing	0
hormone	0
secretion	0
are	0
dependent	0
on	0
estradiol	1
.	0
Hyperprolactinemia	3
can	0
reduce	0
fertility	0
and	0
libido	0
.	0
Although	0
central	0
prolactin	0
actions	0
are	0
thought	0
to	0
contribute	0
to	0
this	0
","	0
the	0
mechanisms	0
are	0
poorly	0
understood	0
.	0
We	0
first	0
tested	0
whether	0
chronic	0
hyperprolactinemia	3
inhibited	0
two	0
neuroendocrine	0
parameters	0
necessary	0
for	0
female	0
fertility	0
:	0
pulsatile	0
LH	0
secretion	0
and	0
the	0
estrogen	1
-	0
induced	0
LH	0
surge	0
.	0
Chronic	0
hyperprolactinemia	3
induced	0
by	0
the	0
dopamine	1
antagonist	0
sulpiride	1
caused	0
a	0
40	0
%	0
reduction	0
LH	0
pulse	0
frequency	0
in	0
ovariectomized	0
rats	0
","	0
but	0
only	0
in	0
the	0
presence	0
of	0
chronic	0
low	0
levels	0
of	0
estradiol	1
.	0
Sulpiride	1
did	0
not	0
affect	0
the	0
magnitude	0
of	0
a	0
steroid	1
-	0
induced	0
LH	0
surge	0
or	0
the	0
percentage	0
of	0
GnRH	0
neurons	0
activated	0
during	0
the	0
surge	0
.	0
Estradiol	1
is	0
known	0
to	0
influence	0
expression	0
of	0
the	0
long	0
form	0
of	0
prolactin	0
receptors	0
(	0
PRL	0
-	0
R	0
)	0
and	0
components	0
of	0
prolactin	0
'	0
s	0
signaling	0
pathway	0
.	0
To	0
test	0
the	0
hypothesis	0
that	0
estrogen	1
increases	0
PRL	0
-	0
R	0
expression	0
and	0
sensitivity	0
to	0
prolactin	0
","	0
we	0
next	0
demonstrated	0
that	0
estradiol	1
greatly	0
augments	0
prolactin	0
-	0
induced	0
STAT5	0
activation	0
.	0
Lastly	0
","	0
we	0
measured	0
PRL	0
-	0
R	0
and	0
suppressor	0
of	0
cytokine	0
signaling	0
(	0
S0CS	0
-	0
1	0
and	0
-	0
3	0
and	0
CIS	0
","	0
which	0
reflect	0
the	0
level	0
of	0
prolactin	0
signaling	0
)	0
mRNAs	0
in	0
response	0
to	0
sulpiride	1
and	0
estradiol	1
.	0
Sulpiride	1
induced	0
only	0
S0CS	0
-	0
1	0
in	0
the	0
medial	0
preoptic	0
area	0
","	0
where	0
GnRH	0
neurons	0
are	0
regulated	0
","	0
but	0
in	0
the	0
arcuate	0
nucleus	0
and	0
choroid	0
plexus	0
","	0
PRL	0
-	0
R	0
","	0
S0CS	0
-	0
3	0
","	0
and	0
CIS	0
mRNA	0
levels	0
were	0
also	0
induced	0
.	0
Estradiol	1
enhanced	0
these	0
effects	0
on	0
S0CS	0
-	0
3	0
and	0
CIS	0
.	0
Interestingly	0
","	0
estradiol	1
also	0
induced	0
PRL	0
-	0
R	0
","	0
S0CS	0
-	0
3	0
","	0
and	0
CIS	0
mRNA	0
levels	0
independently	0
.	0
These	0
data	0
show	0
that	0
GnRH	0
pulse	0
frequency	0
is	0
inhibited	0
by	0
chronic	0
hyperprolactinemia	3
in	0
a	0
steroid	1
-	0
dependent	0
manner	0
.	0
They	0
also	0
provide	0
evidence	0
for	0
estradiol	1
-	0
dependent	0
and	0
brain	0
region	0
-	0
specific	0
regulation	0
of	0
PRL	0
-	0
R	0
expression	0
and	0
signaling	0
responses	0
by	0
prolactin	0
.	0
Clonidine	1
for	0
attention	3
-	4
deficit	4
/	4
hyperactivity	4
disorder	4
:	0
II	0
.	0
ECG	0
changes	0
and	0
adverse	0
events	0
analysis	0
.	0
0BJECTIVE	0
:	0
To	0
examine	0
the	0
safety	0
and	0
tolerability	0
of	0
clonidine	1
used	0
alone	0
or	0
with	0
methylphenidate	1
in	0
children	0
with	0
attention	3
-	4
deficit	4
/	4
hyperactivity	4
disorder	4
(	0
ADHD	3
)	0
.	0
METH0D	0
:	0
In	0
a	0
16	0
-	0
week	0
multicenter	0
","	0
double	0
-	0
blind	0
trial	0
","	0
122	0
children	0
with	0
ADHD	3
were	0
randomly	0
assigned	0
to	0
clonidine	1
(	0
n	0
=	0
31	0
)	0
","	0
methylphenidate	1
(	0
n	0
=	0
29	0
)	0
","	0
clonidine	1
and	0
methylphenidate	1
(	0
n	0
=	0
32	0
)	0
","	0
or	0
placebo	0
(	0
n	0
=	0
30	0
)	0
.	0
Doses	0
were	0
flexibly	0
titrated	0
up	0
to	0
0	0
.	0
6	0
mg	0
/	0
day	0
for	0
clonidine	1
and	0
60	0
mg	0
/	0
day	0
for	0
methylphenidate	1
(	0
both	0
with	0
divided	0
dosing	0
)	0
.	0
Groups	0
were	0
compared	0
regarding	0
adverse	0
events	0
and	0
changes	0
from	0
baseline	0
to	0
week	0
16	0
in	0
electrocardiograms	0
and	0
vital	0
signs	0
.	0
RESULTS	0
:	0
There	0
were	0
more	0
incidents	0
of	0
bradycardia	3
in	0
subjects	0
treated	0
with	0
clonidine	1
compared	0
with	0
those	0
not	0
treated	0
with	0
clonidine	1
(	0
17	0
.	0
5	0
%	0
versus	0
3	0
.	0
4	0
%	0
;	0
p	0
=	0
.	0
2	0
)	0
","	0
but	0
no	0
other	0
significant	0
group	0
differences	0
regarding	0
electrocardiogram	0
and	0
other	0
cardiovascular	0
outcomes	0
.	0
There	0
were	0
no	0
suggestions	0
of	0
interactions	0
between	0
clonidine	1
and	0
methylphenidate	1
regarding	0
cardiovascular	0
outcomes	0
.	0
Moderate	0
or	0
severe	0
adverse	0
events	0
were	0
more	0
common	0
in	0
subjects	0
on	0
clonidine	1
(	0
79	0
.	0
4	0
%	0
versus	0
49	0
.	0
2	0
%	0
;	0
p	0
=	0
.	0
6	0
)	0
but	0
not	0
associated	0
with	0
higher	0
rates	0
of	0
early	0
study	0
withdrawal	0
.	0
Drowsiness	3
was	0
common	0
on	0
clonidine	1
","	0
but	0
generally	0
resolved	0
by	0
6	0
to	0
8	0
weeks	0
.	0
C0NCLUSI0NS	0
:	0
Clonidine	1
","	0
used	0
alone	0
or	0
with	0
methylphenidate	1
","	0
appears	0
safe	0
and	0
well	0
tolerated	0
in	0
childhood	0
ADHD	3
.	0
Physicians	0
prescribing	0
clonidine	1
should	0
monitor	0
for	0
bradycardia	3
and	0
advise	0
patients	0
about	0
the	0
high	0
likelihood	0
of	0
initial	0
drowsiness	3
.	0
Renal	3
Fanconi	4
syndrome	4
and	0
myopathy	3
after	0
liver	0
transplantation	0
:	0
drug	0
-	0
related	0
mitochondrial	3
cytopathy	4
?	0
Advances	0
in	0
the	0
field	0
of	0
transplantation	0
provide	0
a	0
better	0
quality	0
of	0
life	0
and	0
allow	0
more	0
favorable	0
conditions	0
for	0
growth	0
and	0
development	0
in	0
children	0
.	0
However	0
","	0
combinations	0
of	0
different	0
therapeutic	0
regimens	0
require	0
consideration	0
of	0
potential	0
adverse	0
reactions	0
.	0
We	0
describe	0
a	0
15	0
-	0
yr	0
-	0
old	0
girl	0
who	0
had	0
orthotopic	0
liver	0
transplantation	0
because	0
of	0
Wilson	3
'	4
s	4
disease	4
.	0
Tacrolimus	1
","	0
MMF	1
","	0
and	0
steroids	1
were	0
given	0
as	0
immunosuppressant	0
.	0
Lamivudine	1
was	0
added	0
because	0
of	0
de	0
nova	0
hepatitis	3
B	4
infection	4
during	0
her	0
follow	0
-	0
up	0
.	0
Three	0
yr	0
after	0
transplantation	0
she	0
developed	0
renal	3
Fanconi	4
syndrome	4
with	0
severe	0
metabolic	3
acidosis	4
","	0
hypophosphatemia	3
","	0
glycosuria	3
","	0
and	0
aminoaciduria	3
.	0
Although	0
tacrolimus	1
was	0
suspected	0
to	0
be	0
the	0
cause	0
of	0
late	0
post	0
-	0
transplant	0
renal	0
acidosis	3
and	0
was	0
replaced	0
by	0
sirolimus	1
","	0
acidosis	3
","	0
and	0
electrolyte	0
imbalance	0
got	0
worse	0
.	0
Proximal	0
muscle	3
weakness	4
has	0
developed	0
during	0
her	0
follow	0
-	0
up	0
.	0
Fanconi	3
syndrome	4
","	0
as	0
well	0
as	0
myopathy	3
","	0
is	0
well	0
recognized	0
in	0
patients	0
with	0
mitochondrial	3
disorders	4
and	0
caused	0
by	0
depletion	0
of	0
mtDNA	0
.	0
We	0
suggest	0
that	0
our	0
patient	0
'	0
s	0
tubular	3
dysfunction	4
and	0
myopathy	3
may	0
have	0
resulted	0
from	0
mitochondrial	3
dysfunction	4
which	0
is	0
triggered	0
by	0
tacrolimus	1
and	0
augmented	0
by	0
lamivudine	1
.	0
Higher	0
optical	0
density	0
of	0
an	0
antigen	0
assay	0
predicts	0
thrombosis	3
in	0
patients	0
with	0
heparin	1
-	0
induced	0
thrombocytopenia	3
.	0
0BJECTIVES	0
:	0
To	0
correlate	0
optical	0
density	0
and	0
percent	0
inhibition	0
of	0
a	0
two	0
-	0
step	0
heparin	1
-	0
induced	0
thrombocytopenia	3
(	0
HIT	3
)	0
antigen	0
assay	0
with	0
thrombosis	3
;	0
the	0
assay	0
utilizes	0
reaction	0
inhibition	0
characteristics	0
of	0
a	0
high	0
heparin	1
concentration	0
.	0
PATIENTS	0
AND	0
METH0DS	0
:	0
Patients	0
with	0
more	0
than	0
50	0
%	0
decrease	0
in	0
platelet	0
count	0
or	0
thrombocytopenia	3
(	0
<	0
150	0
x	0
10	0
(	0
9	0
)	0
/	0
L	0
)	0
after	0
exposure	0
to	0
heparin	1
","	0
who	0
had	0
a	0
positive	0
two	0
-	0
step	0
antigen	0
assay	0
[	0
optical	0
density	0
(	0
0D	0
)	0
>	0
0	0
.	0
4	0
and	0
>	0
50	0
inhibition	0
with	0
high	0
concentration	0
of	0
heparin	1
]	0
were	0
included	0
in	0
the	0
study	0
.	0
RESULTS	0
:	0
Forty	0
of	0
94	0
HIT	3
patients	0
had	0
thrombosis	3
at	0
diagnosis	0
;	0
54	0
/	0
94	0
had	0
isolated	0
-	0
HIT	3
without	0
thrombosis	3
.	0
Eight	0
of	0
the	0
isolated	0
-	0
HIT	3
patients	0
developed	0
thrombosis	3
within	0
the	0
next	0
30	0
d	0
;	0
thus	0
","	0
a	0
total	0
of	0
48	0
patients	0
had	0
thrombosis	3
at	0
day	0
30	0
.	0
At	0
diagnosis	0
there	0
was	0
no	0
significant	0
difference	0
in	0
0D	0
between	0
HIT	3
patients	0
with	0
thrombosis	3
and	0
those	0
with	0
isolated	0
-	0
HIT	3
.	0
However	0
","	0
0D	0
was	0
significantly	0
higher	0
in	0
all	0
patients	0
with	0
thrombosis	3
(	0
n	0
=	0
48	0
","	0
1	0
.	0
34	0
+	0
/	0
-	0
0	0
.	0
89	0
)	0
","	0
including	0
isolated	0
-	0
HIT	3
patients	0
who	0
later	0
developed	0
thrombosis	3
within	0
30	0
d	0
(	0
n	0
=	0
8	0
","	0
1	0
.	0
84	0
+	0
/	0
-	0
0	0
.	0
64	0
)	0
as	0
compared	0
to	0
isolated	0
-	0
HIT	3
patients	0
who	0
did	0
not	0
develop	0
thrombosis	3
(	0
0	0
.	0
96	0
+	0
/	0
-	0
0	0
.	0
75	0
;	0
P	0
=	0
0	0
.	0
11	0
and	0
P	0
=	0
0	0
.	0
8	0
)	0
.	0
The	0
Receiver	0
0perative	0
Characteristic	0
Curve	0
showed	0
that	0
0D	0
>	0
1	0
.	0
27	0
in	0
the	0
isolated	0
-	0
HIT	3
group	0
had	0
a	0
significantly	0
higher	0
chance	0
of	0
developing	0
thrombosis	3
by	0
day	0
30	0
.	0
None	0
of	0
these	0
groups	0
showed	0
significant	0
difference	0
in	0
percent	0
inhibition	0
.	0
Multivariate	0
analysis	0
showed	0
a	0
2	0
.	0
8	0
-	0
fold	0
increased	0
risk	0
of	0
thrombosis	3
in	0
females	0
.	0
Similarly	0
","	0
thrombotic	3
risk	0
increased	0
with	0
age	0
and	0
0D	0
values	0
.	0
C0NCLUSI0N	0
:	0
Higher	0
0D	0
is	0
associated	0
with	0
significant	0
risk	0
of	0
subsequent	0
thrombosis	3
in	0
patients	0
with	0
isolated	0
-	0
HIT	3
;	0
percent	0
inhibition	0
","	0
however	0
","	0
was	0
not	0
predictive	0
.	0
Thalidomide	1
has	0
limited	0
single	0
-	0
agent	0
activity	0
in	0
relapsed	0
or	0
refractory	0
indolent	0
non	3
-	4
Hodgkin	4
lymphomas	4
:	0
a	0
phase	0
II	0
trial	0
of	0
the	0
Cancer	3
and	0
Leukemia	3
Group	0
B	0
.	0
Thalidomide	1
is	0
an	0
immunomodulatory	0
agent	0
with	0
demonstrated	0
activity	0
in	0
multiple	3
myeloma	4
","	0
mantle	3
cell	4
lymphoma	4
and	0
lymphoplasmacytic	3
lymphoma	4
.	0
Its	0
activity	0
is	0
believed	0
to	0
be	0
due	0
modulation	0
of	0
the	0
tumour	3
milieu	0
","	0
including	0
downregulation	0
of	0
angiogenesis	0
and	0
inflammatory	0
cytokines	0
.	0
Between	0
July	0
2001	0
and	0
April	0
2004	0
","	0
24	0
patients	0
with	0
relapsed	0
/	0
refractory	0
indolent	0
lymphomas	3
received	0
thalidomide	1
200	0
mg	0
daily	0
with	0
escalation	0
by	0
100	0
mg	0
daily	0
every	0
1	0
-	0
2	0
weeks	0
as	0
tolerated	0
","	0
up	0
to	0
a	0
maximum	0
of	0
800	0
mg	0
daily	0
.	0
Patients	0
had	0
received	0
a	0
median	0
of	0
2	0
(	0
range	0
","	0
1	0
-	0
4	0
)	0
prior	0
regimens	0
.	0
0f	0
24	0
evaluable	0
patients	0
","	0
two	0
achieved	0
a	0
complete	0
remission	0
and	0
one	0
achieved	0
a	0
partial	0
remission	0
for	0
an	0
overall	0
response	0
rate	0
of	0
12	0
.	0
5	0
%	0
(	0
95	0
%	0
confidence	0
interval	0
:	0
2	0
.	0
6	0
-	0
32	0
.	0
4	0
%	0
)	0
.	0
Eleven	0
patients	0
progressed	0
during	0
therapy	0
.	0
Grade	0
3	0
-	0
4	0
adverse	0
effects	0
included	0
myelosuppression	3
","	0
fatigue	3
","	0
somnolence	3
/	0
depressed	3
mood	4
","	0
neuropathy	3
and	0
dyspnea	3
.	0
0f	0
concern	0
was	0
the	0
occurrence	0
of	0
four	0
thromboembolic	3
events	0
.	0
0ur	0
results	0
failed	0
to	0
demonstrate	0
an	0
important	0
response	0
rate	0
to	0
single	0
agent	0
thalidomide	1
in	0
indolent	0
lymphomas	3
and	0
contrast	0
with	0
the	0
higher	0
activity	0
level	0
reported	0
with	0
the	0
second	0
generation	0
immunomodulatory	0
agent	0
","	0
lenalidomide	1
.	0
Sex	0
differences	0
in	0
NMDA	1
antagonist	0
enhancement	0
of	0
morphine	1
antihyperalgesia	0
in	0
a	0
capsaicin	1
model	0
of	0
persistent	0
pain	3
:	0
comparisons	0
to	0
two	0
models	0
of	0
acute	3
pain	4
.	0
In	0
acute	3
pain	4
models	0
","	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
(	0
NMDA	1
)	0
antagonists	0
enhance	0
the	0
antinociceptive	0
effects	0
of	0
morphine	1
to	0
a	0
greater	0
extent	0
in	0
males	0
than	0
females	0
.	0
The	0
purpose	0
of	0
this	0
investigation	0
was	0
to	0
extend	0
these	0
findings	0
to	0
a	0
persistent	0
pain	3
model	0
which	0
could	0
be	0
distinguished	0
from	0
acute	3
pain	4
models	0
on	0
the	0
basis	0
of	0
the	0
nociceptive	0
fibers	0
activated	0
","	0
neurochemical	0
substrates	0
","	0
and	0
duration	0
of	0
the	0
nociceptive	0
stimulus	0
.	0
To	0
this	0
end	0
","	0
persistent	0
hyperalgesia	3
was	0
induced	0
by	0
administration	0
of	0
capsaicin	1
in	0
the	0
tail	0
of	0
gonadally	0
intact	0
F344	0
rats	0
","	0
following	0
which	0
the	0
tail	0
was	0
immersed	0
in	0
a	0
mildly	0
noxious	0
thermal	0
stimulus	0
","	0
and	0
tail	0
-	0
withdrawal	0
latencies	0
measured	0
.	0
For	0
comparison	0
","	0
tests	0
were	0
conducted	0
in	0
two	0
acute	3
pain	4
models	0
","	0
the	0
hotplate	0
and	0
warm	0
water	0
tail	0
-	0
withdrawal	0
procedures	0
.	0
In	0
males	0
","	0
the	0
non	0
-	0
competitive	0
NMDA	1
antagonist	0
dextromethorphan	1
enhanced	0
the	0
antihyperalgesic	0
effect	0
of	0
low	0
to	0
moderate	0
doses	0
of	0
morphine	1
in	0
a	0
dose	0
-	0
and	0
time	0
-	0
dependent	0
manner	0
.	0
Across	0
the	0
doses	0
and	0
pretreatment	0
times	0
examined	0
","	0
enhancement	0
was	0
not	0
observed	0
in	0
females	0
.	0
Enhancement	0
of	0
morphine	1
antinociception	0
by	0
dextromethorphan	1
was	0
seen	0
in	0
both	0
males	0
and	0
females	0
in	0
the	0
acute	3
pain	4
models	0
","	0
with	0
the	0
magnitude	0
of	0
this	0
effect	0
being	0
greater	0
in	0
males	0
.	0
These	0
findings	0
demonstrate	0
a	0
sexually	0
-	0
dimorphic	0
interaction	0
between	0
NMDA	1
antagonists	0
and	0
morphine	1
in	0
a	0
persistent	0
pain	3
model	0
that	0
can	0
be	0
distinguished	0
from	0
those	0
observed	0
in	0
acute	3
pain	4
models	0
.	0
Development	0
of	0
proteinuria	3
after	0
switch	0
to	0
sirolimus	1
-	0
based	0
immunosuppression	0
in	0
long	0
-	0
term	0
cardiac	0
transplant	0
patients	0
.	0
Calcineurin	0
-	0
inhibitor	0
therapy	0
can	0
lead	0
to	0
renal	3
dysfunction	4
in	0
heart	0
transplantation	0
patients	0
.	0
The	0
novel	0
immunosuppressive	0
(	0
IS	0
)	0
drug	0
sirolmus	1
(	0
Srl	1
)	0
lacks	0
nephrotoxic	3
effects	0
;	0
however	0
","	0
proteinuria	3
associated	0
with	0
Srl	1
has	0
been	0
reported	0
following	0
renal	0
transplantation	0
.	0
In	0
cardiac	0
transplantation	0
","	0
the	0
incidence	0
of	0
proteinuria	3
associated	0
with	0
Srl	1
is	0
unknown	0
.	0
In	0
this	0
study	0
","	0
long	0
-	0
term	0
cardiac	0
transplant	0
patients	0
were	0
switched	0
from	0
cyclosporine	1
to	0
Srl	1
-	0
based	0
IS	0
.	0
Concomitant	0
IS	0
consisted	0
of	0
mycophenolate	1
mofetil	2
+	0
/	0
-	0
steroids	1
.	0
Proteinuria	0
increased	0
significantly	0
from	0
a	0
median	0
of	0
0	0
.	0
13	0
g	0
/	0
day	0
(	0
range	0
0	0
-	0
5	0
.	0
7	0
)	0
preswitch	0
to	0
0	0
.	0
23	0
g	0
/	0
day	0
(	0
0	0
-	0
9	0
.	0
88	0
)	0
at	0
24	0
months	0
postswitch	0
(	0
p	0
=	0
0	0
.	0
24	0
)	0
.	0
Before	0
the	0
switch	0
","	0
11	0
.	0
5	0
%	0
of	0
patients	0
had	0
high	0
-	0
grade	0
proteinuria	3
(	0
>	0
1	0
.	0
0	0
g	0
/	0
day	0
)	0
;	0
this	0
increased	0
to	0
22	0
.	0
9	0
%	0
postswitch	0
(	0
p	0
=	0
0	0
.	0
6	0
)	0
.	0
ACE	1
inhibitor	2
and	0
angiotensin	1
-	2
releasing	2
blocker	2
(	0
ARB	1
)	0
therapy	0
reduced	0
proteinuria	3
development	0
.	0
Patients	0
without	0
proteinuria	3
had	0
increased	0
renal	0
function	0
(	0
median	0
42	0
.	0
5	0
vs	0
.	0
64	0
.	0
1	0
","	0
p	0
=	0
0	0
.	0
25	0
)	0
","	0
whereas	0
patients	0
who	0
developed	0
high	0
-	0
grade	0
proteinuria	3
showed	0
decreased	0
renal	0
function	0
at	0
the	0
end	0
of	0
follow	0
-	0
up	0
(	0
median	0
39	0
.	0
6	0
vs	0
.	0
29	0
.	0
2	0
","	0
p	0
=	0
0	0
.	0
125	0
)	0
.	0
Thus	0
","	0
proteinuria	3
may	0
develop	0
in	0
cardiac	0
transplant	0
patients	0
after	0
switch	0
to	0
Srl	1
","	0
which	0
may	0
have	0
an	0
adverse	0
effect	0
on	0
renal	0
function	0
in	0
these	0
patients	0
.	0
Srl	1
should	0
be	0
used	0
with	0
ACEi	1
/	0
ARB	1
therapy	0
and	0
patients	0
monitored	0
for	0
proteinuria	3
and	0
increased	0
renal	3
dysfunction	4
.	0
Ginsenoside	1
Rg1	2
restores	0
the	0
impairment	3
of	4
learning	4
induced	0
by	0
chronic	0
morphine	1
administration	0
in	0
rats	0
.	0
Rg1	1
","	0
as	0
a	0
ginsenoside	1
extracted	0
from	0
Panax	0
ginseng	0
","	0
could	0
ameliorate	0
spatial	0
learning	3
impairment	4
.	0
Previous	0
studies	0
have	0
demonstrated	0
that	0
Rg1	1
might	0
be	0
a	0
useful	0
agent	0
for	0
the	0
prevention	0
and	0
treatment	0
of	0
the	0
adverse	0
effects	0
of	0
morphine	1
.	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
investigate	0
the	0
effect	0
of	0
Rg1	1
on	0
learning	3
impairment	4
by	0
chronic	0
morphine	1
administration	0
and	0
the	0
mechanism	0
responsible	0
for	0
this	0
effect	0
.	0
Male	0
rats	0
were	0
subcutaneously	0
injected	0
with	0
morphine	1
(	0
10	0
mg	0
/	0
kg	0
)	0
twice	0
a	0
day	0
at	0
12	0
hour	0
intervals	0
for	0
10	0
days	0
","	0
and	0
Rg1	1
(	0
30	0
mg	0
/	0
kg	0
)	0
was	0
intraperitoneally	0
injected	0
2	0
hours	0
after	0
the	0
second	0
injection	0
of	0
morphine	1
once	0
a	0
day	0
for	0
10	0
days	0
.	0
Spatial	0
learning	0
capacity	0
was	0
assessed	0
in	0
the	0
Morris	0
water	0
maze	0
.	0
The	0
results	0
showed	0
that	0
rats	0
treated	0
with	0
Morphine	1
/	0
Rg1	1
decreased	0
escape	0
latency	0
and	0
increased	0
the	0
time	0
spent	0
in	0
platform	0
quadrant	0
and	0
entering	0
frequency	0
.	0
By	0
implantation	0
of	0
electrodes	0
and	0
electrophysiological	0
recording	0
in	0
vivo	0
","	0
the	0
results	0
showed	0
that	0
Rg1	1
restored	0
the	0
long	0
-	0
term	0
potentiation	0
(	0
LTP	0
)	0
impaired	0
by	0
morphine	1
in	0
both	0
freely	0
moving	0
and	0
anaesthetised	0
rats	0
.	0
The	0
electrophysiological	0
recording	0
in	0
vitro	0
showed	0
that	0
Rg1	1
restored	0
the	0
LTP	0
in	0
slices	0
from	0
the	0
rats	0
treated	0
with	0
morphine	1
","	0
but	0
not	0
changed	0
LTP	0
in	0
the	0
slices	0
from	0
normal	0
saline	0
-	0
or	0
morphine	1
/	0
Rg1	1
-	0
treated	0
rats	0
;	0
this	0
restoration	0
could	0
be	0
inhibited	0
by	0
N	1
-	2
methyl	2
-	2
D	2
-	2
aspartate	2
(	0
NMDA	1
)	0
receptor	0
antagonist	0
MK801	1
.	0
We	0
conclude	0
that	0
Rg1	1
may	0
significantly	0
improve	0
the	0
spatial	0
learning	0
capacity	0
impaired	0
by	0
chonic	0
morphine	1
administration	0
and	0
restore	0
the	0
morphine	1
-	0
inhibited	0
LTP	0
.	0
This	0
effect	0
is	0
NMDA	1
receptor	0
dependent	0
.	0
Synthesis	0
of	0
N	1
-	2
pyrimidinyl	2
-	2
2	2
-	2
phenoxyacetamides	2
as	0
adenosine	1
A2A	0
receptor	0
antagonists	0
.	0
A	0
series	0
of	0
N	1
-	2
pyrimidinyl	2
-	2
2	2
-	2
phenoxyacetamide	2
adenosine	1
A	0
(	0
2A	0
)	0
antagonists	0
is	0
described	0
.	0
SAR	0
studies	0
led	0
to	0
compound	0
14	0
with	0
excellent	0
potency	0
(	0
K	0
(	0
i	0
)	0
=	0
0	0
.	0
4	0
nM	0
)	0
","	0
selectivity	0
(	0
A	0
(	0
1	0
)	0
/	0
A	0
(	0
2A	0
)	0
>	0
100	0
)	0
","	0
and	0
efficacy	0
(	0
MED	0
10	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
)	0
in	0
the	0
rat	0
haloperidol	1
-	0
induced	0
catalepsy	3
model	0
for	0
Parkinson	3
'	4
s	4
disease	4
.	0
Evidence	0
for	0
an	0
involvement	0
of	0
D1	0
and	0
D2	0
dopamine	1
receptors	0
in	0
mediating	0
nicotine	1
-	0
induced	0
hyperactivity	3
in	0
rats	0
.	0
Previous	0
studies	0
have	0
suggested	0
that	0
repeated	0
exposure	0
of	0
rats	0
to	0
the	0
drug	0
or	0
to	0
the	0
experimental	0
environment	0
is	0
necessary	0
to	0
observe	0
nicotine	1
-	0
induced	0
locomotor	0
stimulation	0
.	0
In	0
the	0
present	0
study	0
the	0
role	0
of	0
habituation	0
to	0
the	0
experimental	0
environment	0
on	0
the	0
stimulant	0
effect	0
of	0
nicotine	1
in	0
rats	0
was	0
examined	0
.	0
In	0
addition	0
","	0
the	0
role	0
of	0
dopamine	1
receptors	0
in	0
mediating	0
nicotine	1
-	0
induced	0
locomotor	0
stimulation	0
was	0
investigated	0
by	0
examining	0
the	0
effects	0
of	0
selective	0
D1	0
and	0
D2	0
dopamine	1
receptor	0
antagonists	0
on	0
activity	0
induced	0
by	0
nicotine	1
.	0
Locomotor	0
activity	0
was	0
assessed	0
in	0
male	0
Sprague	0
-	0
Dawley	0
rats	0
tested	0
in	0
photocell	0
cages	0
.	0
Nicotine	1
(	0
1	0
.	0
0	0
mg	0
/	0
kg	0
)	0
caused	0
a	0
significant	0
increase	3
in	4
locomotor	4
activity	4
in	0
rats	0
that	0
were	0
habituated	0
to	0
the	0
test	0
environment	0
","	0
but	0
had	0
only	0
a	0
weak	0
and	0
delayed	0
stimulant	0
action	0
in	0
rats	0
that	0
were	0
unfamiliar	0
with	0
the	0
test	0
environment	0
.	0
The	0
stimulant	0
action	0
of	0
nicotine	1
was	0
blocked	0
by	0
the	0
central	0
nicotinic	0
antagonist	0
mecamylamine	1
but	0
not	0
by	0
the	0
peripheral	0
nicotinic	0
blocker	0
hexamethonium	1
","	0
indicating	0
that	0
the	0
response	0
is	0
probably	0
mediated	0
by	0
central	0
nicotinic	0
receptors	0
.	0
Nicotine	1
-	0
induced	0
hyperactivity	3
was	0
blocked	0
by	0
the	0
selective	0
D1	0
antagonist	0
SCH	1
23390	2
","	0
the	0
selective	0
D2	0
antagonist	0
raclopride	1
and	0
the	0
D1	0
/	0
D2	0
antagonist	0
fluphenazine	1
.	0
Pretreatment	0
with	0
the	0
D2	0
agonist	0
PHN0	1
enhanced	0
nicotine	1
-	0
induced	0
hyperactivity	3
","	0
whereas	0
the	0
D1	0
agonist	0
SKF	1
38393	2
had	0
no	0
effect	0
.	0
The	0
results	0
indicate	0
that	0
acute	0
nicotine	1
injection	0
induces	0
a	0
pronounced	0
hyperactivity	3
in	0
rats	0
habituated	0
to	0
the	0
test	0
environment	0
.	0
The	0
effect	0
appears	0
to	0
be	0
mediated	0
by	0
central	0
nicotine	1
receptors	0
","	0
possibly	0
located	0
on	0
dopaminergic	0
neurons	0
","	0
and	0
also	0
requires	0
the	0
activation	0
of	0
both	0
D1	0
and	0
D2	0
dopamine	1
receptors	0
.	0
Central	0
retinal	3
vein	4
occlusion	4
associated	0
with	0
clomiphene	1
-	0
induced	0
ovulation	0
.	0
0BJECTIVE	0
:	0
To	0
report	0
a	0
case	0
of	0
central	0
retinal	3
vein	4
occlusion	4
associated	0
with	0
clomiphene	1
citrate	2
(	0
CC	1
)	0
.	0
DESIGN	0
:	0
Case	0
study	0
.	0
SETTING	0
:	0
0phthalmology	0
clinic	0
of	0
an	0
academic	0
hospital	0
.	0
PATIENT	0
(	0
S	0
)	0
:	0
A	0
36	0
-	0
year	0
-	0
old	0
woman	0
referred	0
from	0
the	0
infertility	3
clinic	0
for	0
blurred	3
vision	4
.	0
INTERVENTI0N	0
(	0
S	0
)	0
:	0
0phthalmic	0
examination	0
after	0
CC	1
therapy	0
.	0
MAIN	0
0UTC0ME	0
MEASURE	0
(	0
S	0
)	0
:	0
Central	0
retinal	3
vein	4
occlusion	4
after	0
ovulation	0
induction	0
with	0
CC	1
.	0
RESULT	0
(	0
S	0
)	0
:	0
A	0
36	0
-	0
year	0
-	0
old	0
Chinese	0
woman	0
developed	0
central	0
retinal	3
vein	4
occlusion	4
after	0
eight	0
courses	0
of	0
CC	1
.	0
A	0
search	0
of	0
the	0
literature	0
on	0
the	0
thromboembolic	3
complications	0
of	0
CC	1
does	0
not	0
include	0
this	0
severe	0
ophthalmic	0
complication	0
","	0
although	0
mild	0
visual	3
disturbance	4
after	0
CC	1
intake	0
is	0
not	0
uncommon	0
.	0
C0NCLUSI0N	0
(	0
S	0
)	0
:	0
This	0
is	0
the	0
first	0
reported	0
case	0
of	0
central	0
retinal	3
vein	4
occlusion	4
after	0
treatment	0
with	0
CC	1
.	0
Extra	0
caution	0
is	0
warranted	0
in	0
treating	0
infertility	3
patients	0
with	0
CC	1
","	0
and	0
patients	0
should	0
be	0
well	0
informed	0
of	0
this	0
side	0
effect	0
before	0
commencement	0
of	0
therapy	0
.	0
Acute	0
bronchodilating	0
effects	0
of	0
ipratropium	1
bromide	2
and	0
theophylline	1
in	0
chronic	3
obstructive	4
pulmonary	4
disease	4
.	0
The	0
bronchodilator	0
effects	0
of	0
a	0
single	0
dose	0
of	0
ipratropium	1
bromide	2
aerosol	0
(	0
36	0
micrograms	0
)	0
and	0
short	0
-	0
acting	0
theophylline	1
tablets	0
(	0
dose	0
titrated	0
to	0
produce	0
serum	0
levels	0
of	0
10	0
-	0
20	0
micrograms	0
/	0
mL	0
)	0
were	0
compared	0
in	0
a	0
double	0
-	0
blind	0
","	0
placebo	0
-	0
controlled	0
crossover	0
study	0
in	0
21	0
patients	0
with	0
stable	0
","	0
chronic	3
obstructive	4
pulmonary	4
disease	4
.	0
Mean	0
peak	0
forced	0
expiratory	0
volume	0
in	0
1	0
second	0
(	0
FEV1	0
)	0
increases	0
over	0
baseline	0
and	0
the	0
proportion	0
of	0
patients	0
attaining	0
at	0
least	0
a	0
15	0
%	0
increase	0
in	0
the	0
FEV1	0
(	0
responders	0
)	0
were	0
31	0
%	0
and	0
90	0
%	0
","	0
respectively	0
","	0
for	0
ipratropium	1
and	0
17	0
%	0
and	0
50	0
%	0
","	0
respectively	0
","	0
for	0
theophylline	1
.	0
The	0
average	0
FEV1	0
increases	0
during	0
the	0
6	0
-	0
hour	0
observation	0
period	0
were	0
18	0
%	0
for	0
ipratropium	1
and	0
8	0
%	0
for	0
theophylline	1
.	0
The	0
mean	0
duration	0
of	0
action	0
was	0
3	0
.	0
8	0
hours	0
with	0
ipratropium	1
and	0
2	0
.	0
4	0
hours	0
with	0
theophylline	1
.	0
While	0
side	0
effects	0
were	0
rare	0
","	0
those	0
experienced	0
after	0
theophylline	1
use	0
did	0
involve	0
the	0
cardiovascular	3
and	4
gastrointestinal	4
systems	4
.	0
These	0
results	0
show	0
that	0
ipratropium	1
is	0
a	0
more	0
potent	0
bronchodilator	0
than	0
oral	0
theophylline	1
in	0
patients	0
with	0
chronic	3
airflow	4
obstruction	4
.	0
Methamphetamine	1
-	0
induced	0
neurotoxicity	3
and	0
microglial	0
activation	0
are	0
not	0
mediated	0
by	0
fractalkine	0
receptor	0
signaling	0
.	0
Methamphetamine	1
(	0
METH	1
)	0
damages	0
dopamine	1
(	0
DA	1
)	0
nerve	0
endings	0
by	0
a	0
process	0
that	0
has	0
been	0
linked	0
to	0
microglial	0
activation	0
but	0
the	0
signaling	0
pathways	0
that	0
mediate	0
this	0
response	0
have	0
not	0
yet	0
been	0
delineated	0
.	0
Cardona	0
et	0
al	0
.	0
[	0
Nat	0
.	0
Neurosci	0
.	0
9	0
(	0
2006	0
)	0
","	0
917	0
]	0
recently	0
identified	0
the	0
microglial	0
-	0
specific	0
fractalkine	0
receptor	0
(	0
CX3CR1	0
)	0
as	0
an	0
important	0
mediator	0
of	0
MPTP	1
-	0
induced	0
neurodegeneration	3
of	0
DA	1
neurons	0
.	0
Because	0
the	0
CNS	3
damage	4
caused	0
by	0
METH	1
and	0
MPTP	1
is	0
highly	0
selective	0
for	0
the	0
DA	1
neuronal	0
system	0
in	0
mouse	0
models	0
of	0
neurotoxicity	3
","	0
we	0
hypothesized	0
that	0
the	0
CX3CR1	0
plays	0
a	0
role	0
in	0
METH	1
-	0
induced	0
neurotoxicity	3
and	0
microglial	0
activation	0
.	0
Mice	0
in	0
which	0
the	0
CX3CR1	0
gene	0
has	0
been	0
deleted	0
and	0
replaced	0
with	0
a	0
cDNA	0
encoding	0
enhanced	0
green	0
fluorescent	0
protein	0
(	0
eGFP	0
)	0
were	0
treated	0
with	0
METH	1
and	0
examined	0
for	0
striatal	0
neurotoxicity	3
.	0
METH	1
depleted	0
DA	1
","	0
caused	0
microglial	0
activation	0
","	0
and	0
increased	0
body	0
temperature	0
in	0
CX3CR1	0
knockout	0
mice	0
to	0
the	0
same	0
extent	0
and	0
over	0
the	0
same	0
time	0
course	0
seen	0
in	0
wild	0
-	0
type	0
controls	0
.	0
The	0
effects	0
of	0
METH	1
in	0
CX3CR1	0
knockout	0
mice	0
were	0
not	0
gender	0
-	0
dependent	0
and	0
did	0
not	0
extend	0
beyond	0
the	0
striatum	0
.	0
Striatal	0
microglia	0
expressing	0
eGFP	0
constitutively	0
show	0
morphological	0
changes	0
after	0
METH	1
that	0
are	0
characteristic	0
of	0
activation	0
.	0
This	0
response	0
was	0
restricted	0
to	0
the	0
striatum	0
and	0
contrasted	0
sharply	0
with	0
unresponsive	0
eGFP	0
-	0
microglia	0
in	0
surrounding	0
brain	0
areas	0
that	0
are	0
not	0
damaged	0
by	0
METH	1
.	0
We	0
conclude	0
from	0
these	0
studies	0
that	0
CX3CR1	0
signaling	0
does	0
not	0
modulate	0
METH	1
neurotoxicity	3
or	0
microglial	0
activation	0
.	0
Furthermore	0
","	0
it	0
appears	0
that	0
striatal	0
-	0
resident	0
microglia	0
respond	0
to	0
METH	1
with	0
an	0
activation	0
cascade	0
and	0
then	0
return	0
to	0
a	0
surveying	0
state	0
without	0
undergoing	0
apoptosis	0
or	0
migration	0
.	0
Nicotine	1
-	0
induced	0
nystagmus	3
correlates	0
with	0
midpontine	0
activation	0
.	0
The	0
pathomechanism	0
of	0
nicotine	1
-	0
induced	0
nystagmus	3
(	0
NIN	3
)	0
is	0
unknown	0
.	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
delineate	0
brain	0
structures	0
that	0
are	0
involved	0
in	0
NIN	3
generation	0
.	0
Eight	0
healthy	0
volunteers	0
inhaled	0
nicotine	1
in	0
darkness	0
during	0
a	0
functional	0
magnetic	0
resonance	0
imaging	0
(	0
fMRI	0
)	0
experiment	0
;	0
eye	0
movements	0
were	0
registered	0
using	0
video	0
-	0
oculography	0
.	0
NIN	3
correlated	0
with	0
blood	0
oxygen	1
level	0
-	0
dependent	0
(	0
B0LD	0
)	0
activity	0
levels	0
in	0
a	0
midpontine	0
site	0
in	0
the	0
posterior	0
basis	0
pontis	0
.	0
NIN	3
-	0
induced	0
midpontine	0
activation	0
may	0
correspond	0
to	0
activation	0
of	0
the	0
dorsomedial	0
pontine	0
nuclei	0
and	0
the	0
nucleus	0
reticularis	0
tegmenti	0
pontis	0
","	0
structures	0
known	0
to	0
participate	0
in	0
the	0
generation	0
of	0
multidirectional	0
saccades	0
and	0
smooth	0
pursuit	0
eye	0
movements	0
.	0
Acute	0
effects	0
of	0
N	1
-	2
(	2
2	2
-	2
propylpentanoyl	2
)	2
urea	2
on	0
hippocampal	0
amino	1
acid	2
neurotransmitters	0
in	0
pilocarpine	1
-	0
induced	0
seizure	3
in	0
rats	0
.	0
The	0
present	0
study	0
aimed	0
to	0
investigate	0
the	0
anticonvulsant	0
activity	0
as	0
well	0
as	0
the	0
effects	0
on	0
the	0
level	0
of	0
hippocampal	0
amino	1
acid	2
neurotransmitters	0
(	0
glutamate	1
","	0
aspartate	1
","	0
glycine	1
and	0
GABA	1
)	0
of	0
N	1
-	2
(	2
2	2
-	2
propylpentanoyl	2
)	2
urea	2
(	0
VPU	1
)	0
in	0
comparison	0
to	0
its	0
parent	0
compound	0
","	0
valproic	1
acid	2
(	0
VPA	1
)	0
.	0
VPU	1
was	0
more	0
potent	0
than	0
VPA	1
","	0
exhibiting	0
the	0
median	0
effective	0
dose	0
(	0
ED	0
(	0
50	0
)	0
)	0
of	0
49	0
mg	0
/	0
kg	0
in	0
protecting	0
rats	0
against	0
pilocarpine	1
-	0
induced	0
seizure	3
whereas	0
the	0
corresponding	0
value	0
for	0
VPA	1
was	0
322	0
mg	0
/	0
kg	0
.	0
In	0
vivo	0
microdialysis	0
demonstrated	0
that	0
an	0
intraperitoneal	0
administration	0
of	0
pilocarpine	1
induced	0
a	0
pronounced	0
increment	0
of	0
hippocampal	0
glutamate	1
and	0
aspartate	1
whereas	0
no	0
significant	0
change	0
was	0
observed	0
on	0
the	0
level	0
of	0
glycine	1
and	0
GABA	1
.	0
Pretreatment	0
with	0
either	0
VPU	1
(	0
50	0
and	0
100	0
mg	0
/	0
kg	0
)	0
or	0
VPA	1
(	0
300	0
and	0
600	0
mg	0
/	0
kg	0
)	0
completely	0
abolished	0
pilocarpine	1
-	0
evoked	0
increases	0
in	0
extracellular	0
glutamate	1
and	0
aspartate	1
.	0
In	0
addition	0
","	0
a	0
statistically	0
significant	0
reduction	0
was	0
also	0
observed	0
on	0
the	0
level	0
of	0
GABA	1
and	0
glycine	1
but	0
less	0
than	0
a	0
drastic	0
reduction	0
of	0
glutamate	1
and	0
aspartate	1
level	0
.	0
Based	0
on	0
the	0
finding	0
that	0
VPU	1
and	0
VPA	1
could	0
protect	0
the	0
animals	0
against	0
pilocarpine	1
-	0
induced	0
seizure	3
it	0
is	0
suggested	0
that	0
the	0
reduction	0
of	0
inhibitory	0
amino	1
acid	2
neurotransmitters	0
was	0
comparatively	0
minor	0
and	0
offset	0
by	0
a	0
pronounced	0
reduction	0
of	0
glutamate	1
and	0
aspartate	1
.	0
Therefore	0
","	0
like	0
VPA	1
","	0
the	0
finding	0
that	0
VPU	1
could	0
drastically	0
reduce	0
pilocarpine	1
-	0
induced	0
increases	0
in	0
glutamate	1
and	0
aspartate	1
should	0
account	0
","	0
at	0
least	0
partly	0
","	0
for	0
its	0
anticonvulsant	0
activity	0
observed	0
in	0
pilocarpine	1
-	0
induced	0
seizure	3
in	0
experimental	0
animals	0
.	0
Some	0
other	0
mechanism	0
than	0
those	0
being	0
reported	0
herein	0
should	0
be	0
further	0
investigated	0
.	0
Protective	0
effect	0
of	0
verapamil	1
on	0
gastric	3
hemorrhagic	4
ulcers	3
in	0
severe	0
atherosclerotic	3
rats	0
.	0
Studies	0
concerning	0
with	0
pathogenesis	0
of	0
gastric	3
hemorrhage	4
and	0
mucosal	0
ulceration	0
produced	0
in	0
atherosclerotic	3
rats	0
are	0
lacking	0
.	0
The	0
aim	0
of	0
this	0
study	0
is	0
to	0
examine	0
the	0
role	0
of	0
gastric	0
acid	0
back	0
-	0
diffusion	0
","	0
mast	0
cell	0
histamine	1
release	0
","	0
lipid	0
peroxide	0
(	0
LP0	0
)	0
generation	0
and	0
mucosal	0
microvascular	0
permeability	0
in	0
modulating	0
gastric	3
hemorrhage	4
and	0
ulcer	3
in	0
rats	0
with	0
atherosclerosis	3
induced	0
by	0
coadministration	0
of	0
vitamin	1
D2	2
and	0
cholesterol	1
.	0
Additionally	0
","	0
the	0
protective	0
effect	0
of	0
verapamil	1
on	0
this	0
ulcer	3
model	0
was	0
evaluated	0
.	0
Male	0
Wistar	0
rats	0
were	0
challenged	0
intragastrically	0
once	0
daily	0
for	0
9	0
days	0
with	0
1	0
.	0
0	0
ml	0
/	0
kg	0
of	0
corn	0
oil	0
containing	0
vitamin	1
D2	2
and	0
cholesterol	1
to	0
induce	0
atherosclerosis	3
.	0
Control	0
rats	0
received	0
corn	0
oil	0
only	0
.	0
After	0
gastric	0
surgery	0
","	0
rat	0
stomachs	0
were	0
irrigated	0
for	0
3	0
h	0
with	0
either	0
simulated	0
gastric	0
juice	0
or	0
normal	0
saline	0
.	0
Gastric	0
acid	0
back	0
-	0
diffusion	0
","	0
mucosal	0
LP0	0
generation	0
","	0
histamine	1
concentration	0
","	0
microvascular	0
permeability	0
","	0
luminal	1
hemoglobin	0
content	0
and	0
ulcer	3
areas	0
were	0
determined	0
.	0
Elevated	0
atherosclerotic	3
parameters	0
","	0
such	0
as	0
serum	0
calcium	1
","	0
total	0
cholesterol	1
and	0
low	0
-	0
density	0
lipoprotein	0
concentration	0
were	0
obtained	0
in	0
atherosclerotic	3
rats	0
.	0
Severe	0
gastric	0
ulcers	3
accompanied	0
with	0
increased	0
ulcerogenic	0
factors	0
","	0
including	0
gastric	0
acid	0
back	0
-	0
diffusion	0
","	0
histamine	1
release	0
","	0
LP0	0
generation	0
and	0
luminal	1
hemoglobin	0
content	0
were	0
also	0
observed	0
in	0
these	0
rats	0
.	0
Moreover	0
","	0
a	0
positive	0
correlation	0
of	0
histamine	1
to	0
gastric	3
hemorrhage	4
and	0
to	0
ulcer	3
was	0
found	0
in	0
those	0
atherosclerotic	3
rats	0
.	0
This	0
hemorrhagic	3
ulcer	3
and	0
various	0
ulcerogenic	0
parameters	0
were	0
dose	0
-	0
dependently	0
ameliorated	0
by	0
daily	0
intragastric	0
verapamil	1
.	0
Atherosclerosis	3
could	0
produce	0
gastric	3
hemorrhagic	4
ulcer	3
via	0
aggravation	0
of	0
gastric	0
acid	0
back	0
-	0
diffusion	0
","	0
LP0	0
generation	0
","	0
histamine	1
release	0
and	0
microvascular	0
permeability	0
that	0
could	0
be	0
ameliorated	0
by	0
verapamil	1
in	0
rats	0
.	0
Lamivudine	1
for	0
the	0
prevention	0
of	0
hepatitis	3
B	4
virus	0
reactivation	0
in	0
hepatitis	1
-	2
B	2
surface	2
antigen	2
(	0
HBSAG	1
)	0
seropositive	0
cancer	3
patients	0
undergoing	0
cytotoxic	0
chemotherapy	0
.	0
Hepatitis	3
B	4
virus	0
(	0
HBV	0
)	0
is	0
one	0
of	0
the	0
major	0
causes	0
of	0
chronic	0
liver	3
disease	4
worldwide	0
.	0
Cancer	3
patients	0
who	0
are	0
chronic	0
carriers	0
of	0
HBV	0
have	0
a	0
higher	0
hepatic	3
complication	4
rate	0
while	0
receiving	0
cytotoxic	0
chemotherapy	0
(	0
CT	0
)	0
and	0
this	0
has	0
mainly	0
been	0
attributed	0
to	0
HBV	0
reactivation	0
.	0
In	0
this	0
study	0
","	0
cancer	3
patients	0
who	0
have	0
solid	0
and	0
hematological	3
malignancies	4
with	0
chronic	0
HBV	3
infection	4
received	0
the	0
antiviral	0
agent	0
lamivudine	1
prior	0
and	0
during	0
CT	0
compared	0
with	0
historical	0
control	0
group	0
who	0
did	0
not	0
receive	0
lamivudine	1
.	0
The	0
objectives	0
were	0
to	0
assess	0
the	0
efficacy	0
of	0
lamivudine	1
in	0
reducing	0
the	0
incidence	0
of	0
HBV	0
reactivation	0
","	0
and	0
diminishing	0
morbidity	0
and	0
mortality	0
during	0
CT	0
.	0
Two	0
groups	0
were	0
compared	0
in	0
this	0
study	0
.	0
The	0
prophylactic	0
lamivudin	1
group	0
consisted	0
of	0
37	0
patients	0
who	0
received	0
prophylactic	0
lamivudine	1
treatment	0
.	0
The	0
historical	0
controls	0
consisted	0
of	0
50	0
consecutive	0
patients	0
who	0
underwent	0
CT	0
without	0
prophylactic	0
lamivudine	1
.	0
They	0
were	0
followed	0
up	0
during	0
and	0
for	0
8	0
weeks	0
after	0
CT	0
.	0
The	0
outcomes	0
were	0
compared	0
for	0
both	0
groups	0
.	0
0f	0
our	0
control	0
group	0
(	0
n	0
=	0
50	0
)	0
","	0
21	0
patients	0
(	0
42	0
%	0
)	0
were	0
established	0
hepatitis	3
.	0
Twelve	0
(	0
24	0
%	0
)	0
of	0
them	0
were	0
evaluated	0
as	0
severe	0
hepatitis	3
.	0
In	0
the	0
prophylactic	0
lamivudine	1
group	0
severe	0
hepatitis	3
were	0
observed	0
only	0
in	0
1	0
patient	0
(	0
2	0
.	0
7	0
%	0
)	0
of	0
37	0
patients	0
(	0
p	0
<	0
0	0
.	0
6	0
)	0
.	0
Comparison	0
of	0
the	0
mean	0
ALT	0
values	0
revealed	0
significantly	0
higher	0
mean	0
alanine	1
aminotransferase	0
(	0
ALT	0
)	0
values	0
in	0
the	0
control	0
group	0
than	0
the	0
prophylactic	0
lamivudine	1
group	0
;	0
154	0
:	0
64	0
(	0
p	0
<	0
0	0
.	0
32	0
)	0
.	0
0ur	0
study	0
suggests	0
that	0
prophylactic	0
lamivudine	1
significantly	0
decreases	0
the	0
incidence	0
of	0
HBV	0
reactivation	0
and	0
overall	0
morbidity	0
in	0
cancer	3
patients	0
during	0
and	0
after	0
immunosuppressive	0
therapy	0
.	0
Further	0
studies	0
are	0
needed	0
to	0
determine	0
the	0
most	0
appropriate	0
nucleoside	1
or	0
nucleotide	1
analogue	0
for	0
antiviral	0
prophylaxis	0
during	0
CT	0
and	0
the	0
optimal	0
duration	0
of	0
administration	0
after	0
completion	0
of	0
CT	0
.	0
Recovery	0
of	0
tacrolimus	1
-	0
associated	0
brachial	3
neuritis	4
after	0
conversion	0
to	0
everolimus	1
in	0
a	0
pediatric	0
renal	0
transplant	0
recipient	0
-	0
-	0
case	0
report	0
and	0
review	0
of	0
the	0
literature	0
.	0
TAC	1
has	0
been	0
shown	0
to	0
be	0
a	0
potent	0
immunosuppressive	0
agent	0
for	0
solid	0
organ	0
transplantation	0
in	0
pediatrics	0
.	0
Neurotoxicity	3
is	0
a	0
potentially	0
serious	0
toxic	0
effect	0
.	0
It	0
is	0
characterized	0
by	0
encephalopathy	3
","	0
headaches	3
","	0
seizures	3
","	0
or	0
neurological	3
deficits	4
.	0
Here	0
","	0
we	0
describe	0
an	0
eight	0
-	0
and	0
-	0
a	0
-	0
half	0
-	0
yr	0
-	0
old	0
male	0
renal	0
transplant	0
recipient	0
with	0
right	0
BN	0
.	0
MRI	0
demonstrated	0
hyperintense	0
T2	0
signals	0
in	0
the	0
cervical	0
cord	0
and	0
right	0
brachial	0
plexus	0
roots	0
indicative	0
of	0
both	0
myelitis	3
and	0
right	0
brachial	3
plexitis	4
.	0
Symptoms	0
persisted	0
for	0
three	0
months	0
despite	0
TAC	1
dose	0
reduction	0
","	0
administration	0
of	0
IVIG	0
and	0
four	0
doses	0
of	0
methylprednisolone	1
pulse	0
therapy	0
.	0
Improvement	0
and	0
eventually	0
full	0
recovery	0
only	0
occurred	0
after	0
TAC	1
was	0
completely	0
discontinued	0
and	0
successfully	0
replaced	0
by	0
everolimus	1
.	0
0mitting	0
fentanyl	1
reduces	0
nausea	3
and	0
vomiting	3
","	0
without	0
increasing	0
pain	3
","	0
after	0
sevoflurane	1
for	0
day	0
surgery	0
.	0
BACKGR0UND	0
AND	0
0BJECTIVE	0
:	0
Despite	0
advantages	0
of	0
induction	0
and	0
maintenance	0
of	0
anaesthesia	0
with	0
sevoflurane	1
","	0
postoperative	3
nausea	4
and	4
vomiting	4
occurs	0
frequently	0
.	0
Fentanyl	1
is	0
a	0
commonly	0
used	0
supplement	0
that	0
may	0
contribute	0
to	0
this	0
","	0
although	0
it	0
may	0
also	0
improve	0
analgesia	0
.	0
METH0DS	0
:	0
This	0
double	0
-	0
blind	0
study	0
examined	0
the	0
incidence	0
and	0
severity	0
of	0
postoperative	3
nausea	4
and	4
vomiting	4
and	0
pain	3
in	0
the	0
first	0
24	0
h	0
after	0
sevoflurane	1
anaesthesia	0
in	0
216	0
adult	0
day	0
surgery	0
patients	0
.	0
Patients	0
were	0
randomly	0
allocated	0
to	0
either	0
receive	0
or	0
not	0
receive	0
1	0
1	0
fentanyl	1
","	0
while	0
a	0
third	0
group	0
received	0
dexamethasone	1
in	0
addition	0
to	0
fentanyl	1
.	0
RESULTS	0
:	0
0mission	0
of	0
fentanyl	1
did	0
not	0
reduce	0
the	0
overall	0
incidence	0
of	0
postoperative	3
nausea	4
and	4
vomiting	4
","	0
but	0
did	0
reduce	0
the	0
incidence	0
of	0
vomiting	3
and	0
/	0
or	0
moderate	0
to	0
severe	0
nausea	3
prior	0
to	0
discharge	0
from	0
20	0
%	0
and	0
17	0
%	0
with	0
fentanyl	1
and	0
fentanyl	1
-	0
dexamethasone	1
","	0
respectively	0
","	0
to	0
5	0
%	0
(	0
P	0
=	0
0	0
.	0
13	0
)	0
.	0
Antiemetic	0
requirements	0
were	0
reduced	0
from	0
24	0
%	0
and	0
31	0
%	0
to	0
7	0
%	0
(	0
P	0
=	0
0	0
.	0
12	0
)	0
.	0
Dexamethasone	1
had	0
no	0
significant	0
effect	0
on	0
the	0
incidence	0
or	0
severity	0
of	0
postoperative	3
nausea	4
and	4
vomiting	4
.	0
Combining	0
the	0
two	0
fentanyl	1
groups	0
revealed	0
further	0
significant	0
benefits	0
from	0
the	0
avoidance	0
of	0
opioids	0
","	0
reducing	0
postoperative	3
nausea	4
and	4
vomiting	4
and	0
nausea	3
prior	0
to	0
discharge	0
from	0
35	0
%	0
and	0
33	0
%	0
to	0
22	0
%	0
and	0
19	0
%	0
(	0
P	0
=	0
0	0
.	0
49	0
and	0
P	0
=	0
0	0
.	0
35	0
)	0
","	0
respectively	0
","	0
while	0
nausea	3
in	0
the	0
first	0
24	0
h	0
was	0
decreased	0
from	0
42	0
%	0
to	0
27	0
%	0
(	0
P	0
=	0
0	0
.	0
34	0
)	0
.	0
Pain	3
severity	0
and	0
analgesic	0
requirements	0
were	0
unaffected	0
by	0
the	0
omission	0
of	0
fentanyl	1
.	0
Fentanyl	1
did	0
reduce	0
minor	0
intraoperative	0
movement	0
but	0
had	0
no	0
sevoflurane	1
-	0
sparing	0
effect	0
and	0
increased	0
respiratory	3
depression	4
","	0
hypotension	3
and	0
bradycardia	3
.	0
C0NCLUSI0N	0
:	0
As	0
fentanyl	1
exacerbated	0
postoperative	3
nausea	4
and	4
vomiting	4
without	0
an	0
improvement	0
in	0
postoperative	3
pain	4
and	0
also	0
had	0
adverse	0
cardiorespiratory	0
effects	0
","	0
it	0
appears	0
to	0
be	0
an	0
unnecessary	0
and	0
possibly	0
detrimental	0
supplement	0
to	0
sevoflurane	1
in	0
day	0
surgery	0
.	0
Valvular	3
heart	4
disease	4
in	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
treated	0
with	0
pergolide	1
.	0
Course	0
following	0
treatment	0
modifications	0
.	0
Valvular	3
heart	4
abnormalities	4
have	0
been	0
reported	0
in	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
treated	0
with	0
pergolide	1
.	0
However	0
","	0
the	0
incidence	0
and	0
severity	0
of	0
these	0
abnormalities	0
vary	0
from	0
study	0
to	0
study	0
and	0
their	0
course	0
after	0
drug	0
withdrawal	0
has	0
not	0
been	0
systematically	0
assessed	0
.	0
0BJECTIVES	0
:	0
To	0
estimate	0
the	0
frequency	0
and	0
severity	0
of	0
valvular	3
heart	4
abnormality	4
and	0
its	0
possible	0
reversibility	0
after	0
drug	0
withdrawal	0
in	0
a	0
case	0
-	0
control	0
study	0
.	0
METH0DS	0
:	0
All	0
PD	3
patients	0
in	0
the	0
Amiens	0
area	0
treated	0
with	0
pergolide	1
were	0
invited	0
to	0
attend	0
a	0
cardiologic	0
assessment	0
including	0
transthoracic	0
echocardiography	0
.	0
Thirty	0
PD	3
patients	0
participated	0
in	0
the	0
study	0
.	0
A	0
second	0
echocardiography	0
was	0
performed	0
(	0
median	0
interval	0
:	0
13	0
months	0
)	0
after	0
pergolide	1
withdrawal	0
(	0
n	0
=	0
10	0
patients	0
)	0
.	0
Controls	0
were	0
age	0
-	0
and	0
sex	0
-	0
matched	0
non	0
-	0
PD	3
patients	0
referred	0
to	0
the	0
cardiology	0
department	0
.	0
RESULTS	0
:	0
Compared	0
to	0
controls	0
","	0
aortic	3
regurgitation	4
(	0
0R	0
:	0
3	0
.	0
1	0
;	0
95	0
%	0
IC	0
:	0
1	0
.	0
1	0
-	0
8	0
.	0
8	0
)	0
and	0
mitral	3
regurgitation	4
(	0
0R	0
:	0
10	0
.	0
7	0
;	0
95	0
%	0
IC	0
:	0
2	0
.	0
1	0
-	0
53	0
)	0
were	0
more	0
frequent	0
in	0
PD	3
patients	0
(	0
tricuspid	0
:	0
NS	0
)	0
.	0
The	0
number	0
of	0
affected	0
valves	0
(	0
n	0
=	0
2	0
.	0
4	0
+	0
/	0
-	0
0	0
.	0
7	0
)	0
and	0
the	0
sum	0
of	0
regurgitation	0
grades	0
(	0
n	0
=	0
2	0
.	0
8	0
+	0
/	0
-	0
1	0
.	0
9	0
)	0
were	0
higher	0
(	0
p	0
=	0
0	0
.	0
8	0
and	0
p	0
=	0
0	0
.	0
6	0
","	0
respectively	0
)	0
in	0
the	0
pergolide	1
group	0
.	0
Severity	0
of	0
regurgitation	0
was	0
not	0
correlated	0
with	0
pergolide	1
cumulative	0
dose	0
.	0
A	0
restrictive	0
pattern	0
of	0
valvular	3
regurgitation	4
","	0
suggestive	0
of	0
the	0
role	0
of	0
pergolide	1
","	0
was	0
observed	0
in	0
12	0
/	0
30	0
(	0
40	0
%	0
)	0
patients	0
including	0
two	0
with	0
heart	3
failure	4
.	0
Pergolide	1
was	0
discontinued	0
in	0
10	0
patients	0
with	0
valvular	3
heart	4
disease	4
","	0
resulting	0
in	0
a	0
lower	0
regurgitation	0
grade	0
(	0
p	0
=	0
0	0
.	0
1	0
)	0
at	0
the	0
second	0
transthoracic	0
echocardiography	0
and	0
the	0
two	0
patients	0
with	0
heart	3
failure	4
returned	0
to	0
nearly	0
normal	0
clinical	0
examination	0
.	0
This	0
study	0
supports	0
the	0
high	0
frequency	0
of	0
restrictive	0
valve	3
regurgitation	4
in	0
PD	3
patients	0
treated	0
with	0
pergolide	1
and	0
reveals	0
that	0
a	0
significant	0
improvement	0
is	0
usual	0
when	0
the	0
treatment	0
is	0
converted	0
to	0
non	0
-	0
ergot	0
dopamine	1
agonists	0
.	0
Adriamycin	1
-	0
induced	0
autophagic	0
cardiomyocyte	0
death	3
plays	0
a	0
pathogenic	0
role	0
in	0
a	0
rat	0
model	0
of	0
heart	3
failure	4
.	0
BACKGR0UND	0
:	0
The	0
mechanisms	0
underlying	0
heart	3
failure	4
induced	0
by	0
adriamycin	1
are	0
very	0
complicated	0
and	0
still	0
unclear	0
.	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
investigate	0
whether	0
autophagy	0
was	0
involved	0
in	0
the	0
progression	0
of	0
heart	3
failure	4
induced	0
by	0
adriamycin	1
","	0
so	0
that	0
we	0
can	0
develop	0
a	0
novel	0
treatment	0
strategy	0
for	0
heart	3
failure	4
.	0
METH0DS	0
:	0
3	1
-	2
methyladenine	2
(	0
3MA	1
)	0
","	0
a	0
specific	0
inhibitor	0
on	0
autophagy	0
was	0
used	0
in	0
a	0
heart	3
failure	4
model	0
of	0
rats	0
induced	0
by	0
adriamycin	1
.	0
Neonatal	0
cardiomyocytes	0
were	0
isolated	0
from	0
Sprague	0
-	0
Dawley	0
rat	0
hearts	0
and	0
randomly	0
divided	0
into	0
controls	0
","	0
an	0
adriamycin	1
-	0
treated	0
group	0
","	0
and	0
a	0
3MA	1
plus	0
adriamycin	1
-	0
treated	0
group	0
.	0
We	0
then	0
examined	0
the	0
morphology	0
","	0
expression	0
of	0
beclin	0
1	0
gene	0
","	0
mitochondrial	0
permeability	0
transition	0
(	0
MPT	0
)	0
","	0
and	0
Na	0
+	0
-	0
K	1
+	0
ATPase	0
activity	0
in	0
vivo	0
.	0
We	0
also	0
assessed	0
cell	0
viability	0
","	0
mitochondrial	0
membrane	0
potential	0
changes	0
and	0
counted	0
autophagic	0
vacuoles	0
in	0
cultured	0
cardiomyocytes	0
.	0
In	0
addition	0
","	0
we	0
analyzed	0
the	0
expression	0
of	0
autophagy	0
associated	0
gene	0
","	0
beclin	0
1	0
using	0
RT	0
-	0
PCR	0
and	0
Western	0
blotting	0
in	0
an	0
animal	0
model	0
.	0
RESULTS	0
:	0
3MA	1
significantly	0
improved	0
cardiac	0
function	0
and	0
reduced	0
mitochondrial	0
injury	0
.	0
Furthermore	0
","	0
adriamycin	1
induced	0
the	0
formation	0
of	0
autophagic	0
vacuoles	0
","	0
and	0
3MA	1
strongly	0
downregulated	0
the	0
expression	0
of	0
beclin	0
1	0
in	0
adriamycin	1
-	0
induced	0
failing	0
heart	0
and	0
inhibited	0
the	0
formation	0
of	0
autophagic	0
vacuoles	0
.	0
C0NCLUSI0N	0
:	0
Autophagic	0
cardiomyocyte	0
death	3
plays	0
an	0
important	0
role	0
in	0
the	0
pathogenesis	0
of	0
heart	3
failure	4
in	0
rats	0
induced	0
by	0
adriamycin	1
.	0
Mitochondrial	0
injury	0
may	0
be	0
involved	0
in	0
the	0
progression	0
of	0
heart	3
failure	4
caused	0
by	0
adriamycin	1
via	0
the	0
autophagy	0
pathway	0
.	0
mToR	0
inhibitors	0
-	0
induced	0
proteinuria	3
:	0
mechanisms	0
","	0
significance	0
","	0
and	0
management	0
.	0
Massive	0
urinary	0
protein	0
excretion	0
has	0
been	0
observed	0
after	0
conversion	0
from	0
calcineurin	0
inhibitors	0
to	0
mammalian	0
target	0
of	0
rapamycin	1
(	0
mToR	0
)	0
inhibitors	0
","	0
especially	0
sirolimus	1
","	0
in	0
renal	0
transplant	0
recipients	0
with	0
chronic	3
allograft	4
nephropathy	4
.	0
Because	0
proteinuria	3
is	0
a	0
major	0
predictive	0
factor	0
of	0
poor	0
transplantation	0
outcome	0
","	0
many	0
studies	0
focused	0
on	0
this	0
adverse	0
event	0
during	0
the	0
past	0
years	0
.	0
Whether	0
proteinuria	3
was	0
due	0
to	0
sirolimus	1
or	0
only	0
a	0
consequence	0
of	0
calcineurin	0
inhibitors	0
withdrawal	0
remained	0
unsolved	0
until	0
high	0
range	0
proteinuria	3
has	0
been	0
observed	0
during	0
sirolimus	1
therapy	0
in	0
islet	0
transplantation	0
and	0
in	0
patients	0
who	0
received	0
sirolimus	1
de	0
novo	0
.	0
Podocyte	0
injury	0
and	0
focal	0
segmental	0
glomerulosclerosis	3
have	0
been	0
related	0
to	0
mToR	0
inhibition	0
in	0
some	0
patients	0
","	0
but	0
the	0
pathways	0
underlying	0
these	0
lesions	0
remain	0
hypothetic	0
.	0
We	0
discuss	0
herein	0
the	0
possible	0
mechanisms	0
and	0
the	0
significance	0
of	0
mToR	0
blockade	0
-	0
induced	0
proteinuria	3
.	0
Neuropsychiatric	0
side	0
effects	0
after	0
the	0
use	0
of	0
mefloquine	1
.	0
This	0
study	0
describes	0
neuropsychiatric	0
side	0
effects	0
in	0
patients	0
after	0
treatment	0
with	0
mefloquine	1
.	0
Reactions	0
consisted	0
mainly	0
of	0
seizures	3
","	0
acute	0
psychoses	3
","	0
anxiety	3
neurosis	4
","	0
and	0
major	0
disturbances	3
of	4
sleep	4
-	4
wake	4
rhythm	4
.	0
Side	0
effects	0
occurred	0
after	0
both	0
therapeutic	0
and	0
prophylactic	0
intake	0
and	0
were	0
graded	0
from	0
moderate	0
to	0
severe	0
.	0
In	0
a	0
risk	0
analysis	0
of	0
neuropsychiatric	0
side	0
effects	0
in	0
Germany	0
","	0
it	0
is	0
estimated	0
that	0
one	0
of	0
8	0
","	0
0	0
mefloquine	1
users	0
suffers	0
from	0
such	0
reactions	0
.	0
The	0
incidence	0
calculation	0
revealed	0
that	0
one	0
of	0
215	0
therapeutic	0
users	0
had	0
reactions	0
","	0
compared	0
with	0
one	0
of	0
13	0
","	0
0	0
in	0
the	0
prophylaxis	0
group	0
","	0
making	0
the	0
risk	0
of	0
neuropsychiatric	0
reactions	0
after	0
mefloquine	1
treatment	0
60	0
times	0
higher	0
than	0
after	0
prophylaxis	0
.	0
Therefore	0
","	0
certain	0
limitations	0
for	0
malaria	3
prophylaxis	0
and	0
treatment	0
with	0
mefloquine	1
are	0
recommended	0
.	0
Prenatal	0
protein	0
deprivation	0
alters	0
dopamine	1
-	0
mediated	0
behaviors	0
and	0
dopaminergic	0
and	0
glutamatergic	0
receptor	0
binding	0
.	0
Epidemiological	0
evidence	0
indicates	0
that	0
prenatal	0
nutritional	0
deprivation	0
may	0
increase	0
the	0
risk	0
of	0
schizophrenia	3
.	0
The	0
goal	0
of	0
these	0
studies	0
was	0
to	0
use	0
an	0
animal	0
model	0
to	0
examine	0
the	0
effects	0
of	0
prenatal	0
protein	0
deprivation	0
on	0
behaviors	0
and	0
receptor	0
binding	0
with	0
relevance	0
to	0
schizophrenia	3
.	0
We	0
report	0
that	0
prenatally	0
protein	0
deprived	0
(	0
PD	0
)	0
female	0
rats	0
showed	0
an	0
increased	0
stereotypic	0
response	0
to	0
apomorphine	1
and	0
an	0
increased	0
locomotor	0
response	0
to	0
amphetamine	1
in	0
adulthood	0
.	0
These	0
differences	0
were	0
not	0
observed	0
during	0
puberty	0
.	0
No	0
changes	0
in	0
haloperidol	1
-	0
induced	0
catalepsy	3
or	0
MK	1
-	2
801	2
-	0
induced	0
locomotion	0
were	0
seen	0
following	0
PD	0
.	0
In	0
addition	0
","	0
PD	0
female	0
rats	0
showed	0
increased	0
(	0
3	0
)	0
H	1
-	0
MK	1
-	2
801	2
binding	0
in	0
the	0
striatum	0
and	0
hippocampus	0
","	0
but	0
not	0
in	0
the	0
cortex	0
.	0
PD	0
female	0
rats	0
also	0
showed	0
increased	0
(	0
3	0
)	0
H	1
-	0
haloperidol	1
binding	0
and	0
decreased	0
dopamine	1
transporter	0
binding	0
in	0
striatum	0
.	0
No	0
statistically	0
significant	0
changes	0
in	0
behavior	0
or	0
receptor	0
binding	0
were	0
found	0
in	0
PD	0
males	0
with	0
the	0
exception	0
of	0
increased	0
(	0
3	0
)	0
H	1
-	0
MK	1
-	2
801	2
binding	0
in	0
cortex	0
.	0
This	0
animal	0
model	0
may	0
be	0
useful	0
to	0
explore	0
the	0
mechanisms	0
by	0
which	0
prenatal	0
nutritional	3
deficiency	4
enhances	0
risk	0
for	0
schizophrenia	3
in	0
humans	0
and	0
may	0
also	0
have	0
implications	0
for	0
developmental	0
processes	0
leading	0
to	0
differential	0
sensitivity	0
to	0
drugs	0
of	0
abuse	0
.	0
Adverse	0
effects	0
of	0
topical	0
papaverine	1
on	0
auditory	0
nerve	0
function	0
.	0
BACKGR0UND	0
:	0
Papaverine	1
hydrochloride	2
is	0
a	0
direct	0
-	0
acting	0
vasodilator	0
used	0
to	0
manage	0
vasospasm	3
during	0
various	0
neurosurgical	0
operations	0
.	0
Transient	0
cranial	3
nerve	4
dysfunction	4
has	0
been	0
described	0
in	0
a	0
few	0
cases	0
with	0
topical	0
papaverine	1
.	0
This	0
study	0
supports	0
previous	0
reports	0
and	0
provides	0
neurophysiological	0
evidence	0
of	0
an	0
adverse	0
effect	0
on	0
the	0
auditory	0
nerve	0
.	0
METH0DS	0
:	0
We	0
conducted	0
a	0
retrospective	0
review	0
of	0
70	0
consecutive	0
microvascular	0
decompression	0
operations	0
and	0
studied	0
those	0
patients	0
who	0
received	0
topical	0
papaverine	1
for	0
vasospasm	3
.	0
Topical	0
papaverine	1
was	0
used	0
as	0
a	0
direct	0
therapeutic	0
action	0
to	0
manage	0
vasospasm	3
in	0
a	0
total	0
of	0
11	0
patients	0
.	0
The	0
timing	0
of	0
papaverine	1
application	0
and	0
ongoing	0
operative	0
events	0
was	0
reviewed	0
relative	0
to	0
changes	0
in	0
neurophysiological	0
recordings	0
.	0
Brainstem	0
auditory	0
evoked	0
potentials	0
(	0
BAEPs	0
)	0
were	0
routinely	0
used	0
to	0
monitor	0
cochlear	0
nerve	0
function	0
during	0
these	0
operations	0
.	0
FINDINGS	0
:	0
A	0
temporal	0
relationship	0
was	0
found	0
between	0
topical	0
papaverine	1
and	0
BAEP	0
changes	0
leading	0
to	0
complete	0
waveform	0
loss	0
.	0
The	0
average	0
temporal	0
delay	0
between	0
papaverine	1
and	0
the	0
onset	0
of	0
an	0
adverse	0
BAEP	0
change	0
was	0
5	0
min	0
.	0
In	0
10	0
of	0
11	0
patients	0
","	0
BAEP	0
waves	0
II	0
/	0
III	0
-	0
V	0
completely	0
disappeared	0
within	0
2	0
to	0
25	0
min	0
after	0
papaverine	1
.	0
Eight	0
of	0
these	0
10	0
patients	0
had	0
complete	0
loss	0
of	0
BAEP	0
waveforms	0
within	0
10	0
min	0
.	0
0ne	0
patient	0
showed	0
no	0
recovery	0
of	0
later	0
waves	0
and	0
a	0
delayed	0
profound	0
sensorineural	3
hearing	4
loss	4
.	0
The	0
average	0
recovery	0
time	0
of	0
BAEP	0
waveforms	0
to	0
pre	0
-	0
papaverine	1
baseline	0
values	0
was	0
39	0
min	0
.	0
C0NCLUSI0NS	0
:	0
Topical	0
papaverine	1
for	0
the	0
treatment	0
of	0
vasospasm	3
was	0
associated	0
with	0
the	0
onset	0
of	0
a	0
transient	0
disturbance	0
in	0
neurophysiological	0
function	0
of	0
the	0
ascending	0
auditory	0
brainstem	0
pathway	0
.	0
The	0
complete	0
disappearance	0
of	0
BAEP	0
waveforms	0
with	0
a	0
consistent	0
temporal	0
delay	0
suggests	0
a	0
possible	0
adverse	3
effect	4
on	4
the	4
proximal	4
eighth	4
nerve	4
.	0
Recommendations	0
to	0
avoid	0
potential	0
cranial	3
nerve	4
deficits	4
from	0
papaverine	1
are	0
provided	0
.	0
Simvastatin	1
-	2
ezetimibe	2
-	0
induced	0
hepatic	3
failure	4
necessitating	0
liver	0
transplantation	0
.	0
Abstract	0
Serum	0
aminotransferase	0
elevations	0
are	0
a	0
commonly	0
known	0
adverse	0
effect	0
of	0
3	0
-	0
hydroxy	0
-	0
3	0
-	0
methylglutaryl	0
coenzyme	0
A	0
reductase	0
inhibitor	0
(	0
statin	1
)	0
therapy	0
.	0
However	0
","	0
hepatotoxic	3
events	0
have	0
not	0
been	0
widely	0
published	0
with	0
ezetimibe	1
or	0
the	0
combination	0
agent	0
simvastatin	1
-	2
ezetimibe	2
.	0
We	0
describe	0
a	0
70	0
-	0
year	0
-	0
old	0
Hispanic	0
woman	0
who	0
developed	0
fulminant	3
hepatic	4
failure	4
necessitating	0
liver	0
transplantation	0
10	0
weeks	0
after	0
conversion	0
from	0
simvastatin	1
40	0
mg	0
/	0
day	0
to	0
simvastatin	1
10	2
mg	2
-	2
ezetimibe	2
40	2
mg	2
/	0
day	0
.	0
The	0
patient	0
'	0
s	0
lipid	0
panel	0
had	0
been	0
maintained	0
with	0
simvastatin	1
for	0
18	0
months	0
before	0
the	0
conversion	0
without	0
evidence	0
of	0
hepatotoxicity	3
.	0
A	0
routine	0
laboratory	0
work	0
-	0
up	0
10	0
weeks	0
after	0
conversion	0
revealed	0
elevated	0
serum	0
aminotransferase	0
levels	0
.	0
Simvastatinezetimibe	1
and	0
escitalopram	1
(	0
which	0
she	0
was	0
taking	0
for	0
depression	3
)	0
were	0
discontinued	0
","	0
and	0
other	0
potential	0
causes	0
of	0
hepatotoxicity	3
were	0
excluded	0
.	0
A	0
repeat	0
work	0
-	0
up	0
revealed	0
further	0
elevations	0
in	0
aminotransferase	0
levels	0
","	0
and	0
liver	0
biopsy	0
revealed	0
evidence	0
of	0
moderate	0
-	0
to	0
-	0
severe	0
drug	3
toxicity	4
.	0
She	0
underwent	0
liver	0
transplantation	0
with	0
an	0
uneventful	0
postoperative	0
course	0
.	0
Her	0
aminotransferase	0
levels	0
returned	0
to	0
normal	0
by	0
postoperative	0
day	0
23	0
","	0
and	0
her	0
2	0
-	0
year	0
follow	0
-	0
up	0
showed	0
no	0
adverse	0
events	0
.	0
Ezetimibe	1
undergoes	0
extensive	0
glucuronidation	0
by	0
uridine	1
diphosphate	2
glucoronosyltransferases	0
(	0
UGT	0
)	0
in	0
the	0
intestine	0
and	0
liver	0
and	0
may	0
have	0
inhibited	0
the	0
glucuronidation	0
of	0
simvastatin	1
hydroxy	2
acid	2
","	0
resulting	0
in	0
increased	0
simvastatin	1
exposure	0
and	0
subsequent	0
hepatotoxicity	3
.	0
To	0
our	0
knowledge	0
","	0
this	0
is	0
the	0
first	0
case	0
report	0
of	0
simvastatin	1
-	2
ezetimibe	2
-	0
induced	0
liver	3
failure	4
that	0
resulted	0
in	0
liver	0
transplantation	0
.	0
We	0
postulate	0
that	0
the	0
mechanism	0
of	0
the	0
simvastatinezetimibe	1
-	0
induced	0
hepatotoxicity	3
is	0
the	0
increased	0
simvastatin	1
exposure	0
by	0
ezetimibe	1
inhibition	0
of	0
UGT	0
enzymes	0
.	0
Clinicians	0
should	0
be	0
aware	0
of	0
potential	0
hepatotoxicity	3
with	0
simvastatin	1
-	2
ezetimibe	2
especially	0
in	0
elderly	0
patients	0
and	0
should	0
carefully	0
monitor	0
serum	0
aminotransferase	0
levels	0
when	0
starting	0
therapy	0
and	0
titrating	0
the	0
dosage	0
.	0
Massive	0
proteinuria	3
and	0
acute	3
renal	4
failure	4
after	0
oral	0
bisphosphonate	1
(	0
alendronate	1
)	0
administration	0
in	0
a	0
patient	0
with	0
focal	3
segmental	4
glomerulosclerosis	4
.	0
A	0
61	0
-	0
year	0
-	0
old	0
Japanese	0
man	0
with	0
nephrotic	3
syndrome	4
due	0
to	0
focal	3
segmental	4
glomerulosclerosis	4
was	0
initially	0
responding	0
well	0
to	0
steroid	1
therapy	0
.	0
The	0
amount	0
of	0
daily	0
urinary	0
protein	0
decreased	0
from	0
15	0
.	0
6	0
to	0
2	0
.	0
8	0
g	0
.	0
Within	0
14	0
days	0
of	0
the	0
oral	0
bisphosphonate	1
(	0
alendronate	1
sodium	2
)	0
administration	0
","	0
the	0
amount	0
of	0
daily	0
urinary	0
protein	0
increased	0
rapidly	0
up	0
to	0
12	0
.	0
8	0
g	0
with	0
acute	3
renal	4
failure	4
.	0
After	0
discontinuing	0
the	0
oral	0
alendronate	1
","	0
the	0
patient	0
underwent	0
six	0
cycles	0
of	0
hemodialysis	0
and	0
four	0
cycles	0
of	0
LDL	0
apheresis	0
.	0
Urinary	0
volume	0
and	0
serum	0
creatinine	1
levels	0
recovered	0
to	0
the	0
normal	0
range	0
","	0
with	0
urinary	0
protein	0
disappearing	0
completely	0
within	0
40	0
days	0
.	0
This	0
report	0
demonstrates	0
that	0
not	0
only	0
intravenous	0
","	0
but	0
also	0
oral	0
bisphosphonates	1
can	0
aggravate	0
proteinuria	3
and	0
acute	3
renal	4
failure	4
.	0
Serum	0
-	0
and	0
glucocorticoid	0
-	0
inducible	0
kinase	0
1	0
in	0
doxorubicin	1
-	0
induced	0
nephrotic	3
syndrome	4
.	0
Doxorubicin	1
-	0
induced	0
nephropathy	3
leads	0
to	0
epithelial	0
sodium	1
channel	0
(	0
ENaC	0
)	0
-	0
dependent	0
volume	3
retention	4
and	0
renal	0
fibrosis	3
.	0
The	0
aldosterone	1
-	0
sensitive	0
serum	0
-	0
and	0
glucocorticoid	0
-	0
inducible	0
kinase	0
SGK1	0
has	0
been	0
shown	0
to	0
participate	0
in	0
the	0
stimulation	0
of	0
ENaC	0
and	0
to	0
mediate	0
renal	0
fibrosis	3
following	0
mineralocorticoid	0
and	0
salt	0
excess	0
.	0
The	0
present	0
study	0
was	0
performed	0
to	0
elucidate	0
the	0
role	0
of	0
SGK1	0
in	0
the	0
volume	3
retention	4
and	0
fibrosis	3
during	0
nephrotic	3
syndrome	4
.	0
To	0
this	0
end	0
","	0
doxorubicin	1
(	0
15	0
mug	0
/	0
g	0
body	0
wt	0
)	0
was	0
injected	0
intravenously	0
into	0
gene	0
-	0
targeted	0
mice	0
lacking	0
SGK1	0
(	0
sgk1	0
(	0
-	0
/	0
-	0
)	0
)	0
and	0
their	0
wild	0
-	0
type	0
littermates	0
(	0
sgk1	0
(	0
+	0
/	0
+	0
)	0
)	0
.	0
Doxorubicin	1
treatment	0
resulted	0
in	0
heavy	0
proteinuria	3
(	0
>	0
100	0
mg	0
protein	0
/	0
mg	0
crea	0
)	0
in	0
15	0
/	0
44	0
of	0
sgk1	0
(	0
+	0
/	0
+	0
)	0
and	0
15	0
/	0
44	0
of	0
sgk1	0
(	0
-	0
/	0
-	0
)	0
mice	0
leading	0
to	0
severe	0
nephrotic	3
syndrome	4
with	0
ascites	3
","	0
lipidemia	3
","	0
and	0
hypoalbuminemia	3
in	0
both	0
genotypes	0
.	0
Plasma	0
aldosterone	1
levels	0
increased	0
in	0
nephrotic	3
mice	0
of	0
both	0
genotypes	0
and	0
was	0
followed	0
by	0
increased	0
SGK1	0
protein	0
expression	0
in	0
sgk1	0
(	0
+	0
/	0
+	0
)	0
mice	0
.	0
Urinary	0
sodium	1
excretion	0
reached	0
signficantly	0
lower	0
values	0
in	0
sgk1	0
(	0
+	0
/	0
+	0
)	0
mice	0
(	0
15	0
+	0
/	0
-	0
5	0
mumol	0
/	0
mg	0
crea	0
)	0
than	0
in	0
sgk1	0
(	0
-	0
/	0
-	0
)	0
mice	0
(	0
35	0
+	0
/	0
-	0
5	0
mumol	0
/	0
mg	0
crea	0
)	0
and	0
was	0
associated	0
with	0
a	0
significantly	0
higher	0
body	0
weight	3
gain	4
in	0
sgk1	0
(	0
+	0
/	0
+	0
)	0
compared	0
with	0
sgk1	0
(	0
-	0
/	0
-	0
)	0
mice	0
(	0
+	0
6	0
.	0
6	0
+	0
/	0
-	0
0	0
.	0
7	0
vs	0
.	0
+	0
4	0
.	0
1	0
+	0
/	0
-	0
0	0
.	0
8	0
g	0
)	0
.	0
During	0
the	0
course	0
of	0
nephrotic	3
syndrome	4
","	0
serum	0
urea	1
concentrations	0
increased	0
significantly	0
faster	0
in	0
sgk1	0
(	0
-	0
/	0
-	0
)	0
mice	0
than	0
in	0
sgk1	0
(	0
+	0
/	0
+	0
)	0
mice	0
leading	0
to	0
uremia	3
and	0
a	0
reduced	0
median	0
survival	0
in	0
sgk1	0
(	0
-	0
/	0
-	0
)	0
mice	0
(	0
29	0
vs	0
.	0
40	0
days	0
in	0
sgk1	0
(	0
+	0
/	0
+	0
)	0
mice	0
)	0
.	0
In	0
conclusion	0
","	0
gene	0
-	0
targeted	0
mice	0
lacking	0
SGK1	0
showed	0
blunted	0
volume	3
retention	4
","	0
yet	0
were	0
not	0
protected	0
against	0
renal	0
fibrosis	3
during	0
experimental	0
nephrotic	3
syndrome	4
.	0
Severe	0
thrombocytopenia	3
and	0
haemolytic	3
anaemia	4
associated	0
with	0
ciprofloxacin	1
:	0
a	0
case	0
report	0
with	0
fatal	0
outcome	0
.	0
Haematological	0
adverse	0
reactions	0
associated	0
with	0
fatal	0
outcome	0
are	0
rare	0
during	0
treatment	0
with	0
ciprofloxacin	1
.	0
A	0
30	0
-	0
year	0
old	0
Caucasian	0
man	0
reported	0
with	0
abdominal	3
pain	4
and	0
jaundice	3
after	0
3	0
-	0
day	0
administration	0
of	0
oral	0
ciprofloxacin	1
for	0
a	0
suspect	0
of	0
urinary	3
tract	4
infection	4
.	0
Clinical	0
evaluations	0
suggested	0
an	0
initial	0
diagnosis	0
of	0
severe	0
thrombocytopenia	3
and	0
haemolysis	3
.	0
The	0
patient	0
progressively	0
developed	0
petechiae	3
and	0
purpura	3
on	0
thorax	0
and	0
lower	0
limbs	0
.	0
Despite	0
pharmacological	0
and	0
supportive	0
interventions	0
","	0
laboratory	0
parameters	0
worsened	0
and	0
the	0
patient	0
died	0
17	0
hours	0
after	0
admission	0
.	0
An	0
accurate	0
autopsy	0
revealed	0
most	0
organs	0
with	0
diffuse	0
petechial	0
haemorrhages	3
.	0
No	0
signs	0
of	0
bone	3
marrow	4
depression	4
were	0
found	0
.	0
No	0
thrombi	3
or	0
signs	0
of	0
microangiopathies	3
were	0
observed	0
in	0
arterial	0
vessels	0
.	0
Blood	0
and	0
urine	0
cultures	0
did	0
not	0
show	0
any	0
bacterial	0
growth	0
.	0
This	0
case	0
report	0
shows	0
that	0
ciprofloxacin	1
may	0
precipitate	0
life	0
-	0
threatening	0
thrombocytopenia	3
and	0
haemolytic	3
anaemia	4
","	0
even	0
in	0
the	0
early	0
phases	0
of	0
treatment	0
and	0
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","	0
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8	1
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aminoquinoline	2
8	1
-	2
[	2
(	2
4	2
-	2
amino	2
-	2
l	2
-	2
methylbutyl	2
)	2
amino	2
]	2
-	2
5	2
-	2
(	2
l	2
-	2
hexyloxy	2
)	2
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6	2
-	2
methoxy	2
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4	2
-	2
methylquinoline	2
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WR242511	1
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WR242511	1
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WR242511	1
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WR242511	1
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60	0
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WR242511	1
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0	0
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","	0
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levodopa	1
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Parkinson	3
'	4
s	4
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In	0
a	0
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","	0
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","	0
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","	0
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Parkinson	3
'	4
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PD	3
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PD	3
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rTMS	0
(	0
1	0
","	0
800	0
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1	0
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4	0
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","	0
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","	0
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real	0
rTMS	0
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not	0
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.	0
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major	0
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dystonia	3
subscore	0
.	0
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","	0
in	0
patient	0
diaries	0
","	0
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","	0
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3	0
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the	0
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rTMS	0
only	0
.	0
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rTMS	0
","	0
no	0
side	0
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no	0
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motor	0
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PD	3
symptoms	0
were	0
noted	0
.	0
The	0
results	0
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the	0
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residual	0
beneficial	0
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rTMS	0
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dyskinesias	3
in	0
PD	3
.	0
The	0
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potential	0
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.	0
Intracavernous	0
epinephrine	1
:	0
a	0
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priapism	3
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the	0
emergency	0
department	0
.	0
Priapism	3
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the	0
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erection	0
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the	0
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the	0
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sexual	0
arousal	0
.	0
A	0
45	0
-	0
year	0
-	0
old	0
man	0
","	0
an	0
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frequent	0
cocaine	1
user	0
","	0
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the	0
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(	0
ED	0
)	0
on	0
two	0
separate	0
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with	0
a	0
history	0
of	0
priapism	3
after	0
cocaine	1
use	0
.	0
The	0
management	0
options	0
in	0
the	0
ED	0
","	0
as	0
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by	0
four	0
individual	0
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","	0
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the	0
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","	0
are	0
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.	0
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of	0
lamivudine	1
with	0
chronic	0
immunosuppressive	0
therapy	0
for	0
rheumatologic	3
disorders	4
.	0
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objective	0
of	0
this	0
study	0
was	0
to	0
report	0
our	0
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concerning	0
the	0
effectiveness	0
of	0
the	0
prophylactic	0
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of	0
lamivudine	1
in	0
hepatitis	1
B	2
virus	2
surface	2
antigen	2
(	0
HBs	1
Ag	2
)	0
positive	0
patients	0
with	0
rheumatologic	3
disease	4
.	0
From	0
June	0
2004	0
to	0
0ctober	0
2006	0
","	0
11	0
HBs	1
Ag	2
positive	0
patients	0
with	0
rheumatologic	3
diseases	4
","	0
who	0
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on	0
both	0
immunosuppressive	0
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prophylactic	0
lamivudine	1
therapies	0
","	0
were	0
retrospectively	0
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.	0
Liver	0
function	0
tests	0
","	0
hepatitis	3
B	4
virus	0
(	0
HBV	0
)	0
serologic	0
markers	0
","	0
and	0
HBV	0
DNA	0
levels	0
of	0
the	0
patients	0
during	0
follow	0
-	0
up	0
were	0
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from	0
hospital	0
file	0
records	0
.	0
Eleven	0
patients	0
(	0
six	0
male	0
)	0
with	0
median	0
age	0
47	0
years	0
(	0
range	0
27	0
-	0
73	0
)	0
","	0
median	0
disease	0
duration	0
50	0
months	0
(	0
range	0
9	0
-	0
178	0
)	0
and	0
median	0
follow	0
-	0
up	0
period	0
of	0
patients	0
13	0
.	0
8	0
months	0
(	0
range	0
5	0
-	0
27	0
)	0
were	0
enrolled	0
in	0
this	0
study	0
.	0
Lamivudine	1
therapy	0
was	0
started	0
3	0
-	0
7	0
days	0
prior	0
to	0
immunosuppressive	0
therapy	0
in	0
all	0
patients	0
.	0
Baseline	0
","	0
liver	0
function	0
tests	0
were	0
elevated	0
in	0
two	0
patients	0
(	0
fourth	0
patient	0
:	0
ALT	0
:	0
122	0
IU	0
/	0
l	0
","	0
AST	0
:	0
111	0
IU	0
/	0
l	0
","	0
tenth	0
patient	0
:	0
ALT	0
:	0
294	0
IU	0
/	0
l	0
","	0
AST	0
:	0
274	0
IU	0
/	0
l	0
","	0
with	0
minimal	0
changes	0
in	0
the	0
liver	0
biopsy	0
in	0
both	0
)	0
.	0
Shortly	0
after	0
treatment	0
their	0
tests	0
normalized	0
and	0
during	0
follow	0
-	0
up	0
period	0
none	0
of	0
the	0
patients	0
had	0
abnormal	3
liver	4
function	4
tests	0
.	0
In	0
four	0
patients	0
HBV	0
DNA	0
levels	0
were	0
higher	0
than	0
normal	0
at	0
baseline	0
.	0
Two	0
of	0
these	0
normalized	0
and	0
the	0
others	0
increased	0
later	0
.	0
In	0
three	0
additional	0
patients	0
","	0
HBV	0
DNA	0
levels	0
were	0
increased	0
during	0
follow	0
-	0
up	0
.	0
None	0
of	0
the	0
patients	0
had	0
significant	0
clinical	0
sings	0
of	0
HBV	0
activation	0
.	0
Lamivudine	1
was	0
well	0
tolerated	0
and	0
was	0
continued	0
in	0
all	0
patients	0
.	0
Prophylactic	0
administration	0
of	0
lamivudine	1
in	0
patients	0
who	0
required	0
immunosuppressive	0
therapy	0
seems	0
to	0
be	0
safe	0
","	0
well	0
tolerated	0
and	0
effective	0
in	0
preventing	0
HBV	0
reactivation	0
.	0
Effect	0
of	0
green	1
tea	2
and	0
vitamin	1
E	2
combination	0
in	0
isoproterenol	1
induced	0
myocardial	3
infarction	4
in	0
rats	0
.	0
The	0
present	0
study	0
was	0
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to	0
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the	0
combined	0
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of	0
green	1
tea	2
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vitamin	1
E	2
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heart	0
weight	0
","	0
body	0
weight	0
","	0
serum	0
marker	0
enzymes	0
","	0
lipid	0
peroxidation	0
","	0
endogenous	0
antioxidants	0
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membrane	0
bound	0
ATPases	0
in	0
isoproterenol	1
(	0
IS0	1
)	0
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induced	0
myocardial	3
infarction	4
in	0
rats	0
.	0
Adult	0
male	0
albino	0
rats	0
","	0
treated	0
with	0
IS0	1
(	0
200	0
mg	0
/	0
kg	0
","	0
s	0
.	0
c	0
.	0
)	0
for	0
2	0
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at	0
an	0
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of	0
24	0
h	0
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a	0
significant	0
(	0
P	0
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0	0
.	0
5	0
)	0
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heart	0
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","	0
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","	0
lipid	0
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Ca	1
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2	0
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there	0
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a	0
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(	0
P	0
<	0
0	0
.	0
5	0
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","	0
endogenous	0
antioxidants	0
","	0
Na	1
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/	0
K	1
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Mg	1
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2	0
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.	0
Administration	0
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green	1
tea	2
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100	0
mg	0
/	0
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","	0
p	0
.	0
o	0
.	0
)	0
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vitamin	1
E	2
(	0
100	0
mg	0
/	0
kg	0
/	0
day	0
","	0
p	0
.	0
o	0
.	0
)	0
together	0
for	0
30	0
consecutive	0
days	0
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IS0	1
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29th	0
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30th	0
","	0
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(	0
P	0
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0	0
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5	0
)	0
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in	0
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","	0
serum	0
marker	0
enzymes	0
","	0
lipid	0
peroxidation	0
","	0
Ca	1
+	0
2	0
ATPase	0
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the	0
body	0
weight	0
","	0
endogenous	0
antioxidants	0
","	0
Na	1
+	0
/	0
K	1
+	0
ATPase	0
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Mg	1
+	0
2	0
ATPase	0
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IS0	1
treated	0
group	0
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green	1
tea	2
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vitamin	1
E	2
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These	0
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tea	2
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vitamin	1
E	2
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IS0	1
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myocardial	3
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rats	0
.	0
Irreversible	0
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the	0
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nephropathy	3
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F344	0
rats	0
.	0
Renal	3
papillary	4
necrosis	4
(	0
RPN	3
)	0
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a	0
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urinary	0
concentrating	0
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-	0
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aspirin	1
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paracetamol	1
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female	0
Fischer	0
344	0
rats	0
.	0
Renal	0
structure	0
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concentrating	0
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18	0
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","	0
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","	0
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the	0
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medullary	0
interstitial	0
matrix	0
","	0
or	0
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1	0
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cells	0
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the	0
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analgesic	0
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.	0
The	0
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of	0
urinary	0
concentrating	0
ability	0
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the	0
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of	0
analgesic	0
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inner	0
medullary	0
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.	0
During	0
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analgesic	0
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","	0
the	0
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in	0
urinary	0
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","	0
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","	0
maximum	0
urinary	0
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.	0
This	0
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that	0
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analgesic	0
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Fischer	0
344	0
rats	0
causes	0
progressive	0
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irreversible	0
damage	0
to	0
the	0
interstitial	0
matrix	0
and	0
type	0
1	0
interstitial	0
cells	0
leading	0
to	0
RPN	3
.	0
The	0
associated	0
urinary	0
concentrating	0
defect	0
is	0
reversible	0
only	0
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the	0
early	0
stages	0
of	0
structural	0
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to	0
the	0
inner	0
medulla	0
.	0
Testosterone	1
-	0
dependent	0
hypertension	3
and	0
upregulation	0
of	0
intrarenal	0
angiotensinogen	0
in	0
Dahl	0
salt	1
-	0
sensitive	0
rats	0
.	0
Blood	0
pressure	0
(	0
BP	0
)	0
is	0
more	0
salt	1
sensitive	0
in	0
men	0
than	0
in	0
premenopausal	0
women	0
.	0
In	0
Dahl	0
salt	1
-	0
sensitive	0
rats	0
(	0
DS	0
)	0
","	0
high	0
-	0
salt	1
(	0
HS	0
)	0
diet	0
increases	0
BP	0
more	0
in	0
males	0
than	0
females	0
.	0
In	0
contrast	0
to	0
the	0
systemic	0
renin	0
-	0
angiotensin	1
system	0
","	0
which	0
is	0
suppressed	0
in	0
response	0
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HS	0
in	0
male	0
DS	0
","	0
intrarenal	0
angiotensinogen	0
expression	0
is	0
increased	0
","	0
and	0
intrarenal	0
levels	0
of	0
ANG	0
II	0
are	0
not	0
suppressed	0
.	0
In	0
this	0
study	0
","	0
the	0
hypothesis	0
was	0
tested	0
that	0
there	0
is	0
a	0
sexual	0
dimorphism	0
in	0
HS	0
-	0
induced	0
upregulation	0
of	0
intrarenal	0
angiotensinogen	0
mediated	0
by	0
testosterone	1
that	0
also	0
causes	0
increases	0
in	0
BP	0
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renal	3
injury	4
.	0
0n	0
a	0
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-	0
salt	1
(	0
LS	0
)	0
diet	0
","	0
male	0
DS	0
had	0
higher	0
levels	0
of	0
intrarenal	0
angiotensinogen	0
mRNA	0
than	0
females	0
.	0
HS	0
diet	0
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4	0
wk	0
increased	0
renal	0
cortical	0
angiotensinogen	0
mRNA	0
and	0
protein	0
only	0
in	0
male	0
DS	0
","	0
which	0
was	0
prevented	0
by	0
castration	0
.	0
0variectomy	0
of	0
female	0
DS	0
had	0
no	0
effect	0
on	0
intrarenal	0
angiotensinogen	0
expression	0
on	0
either	0
diet	0
.	0
Radiotelemetric	0
BP	0
was	0
similar	0
between	0
males	0
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castrated	0
rats	0
on	0
LS	0
diet	0
.	0
HS	0
diet	0
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4	0
wk	0
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a	0
progressive	0
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in	0
BP	0
","	0
protein	0
and	0
albumin	0
excretion	0
","	0
and	0
glomerular	3
sclerosis	4
in	0
male	0
DS	0
rats	0
","	0
which	0
were	0
attenuated	0
by	0
castration	0
.	0
Testosterone	1
replacement	0
in	0
castrated	0
DS	0
rats	0
increased	0
BP	0
","	0
renal	3
injury	4
","	0
and	0
upregulation	0
of	0
renal	0
angiotensinogen	0
associated	0
with	0
HS	0
diet	0
.	0
Testosterone	1
contributes	0
to	0
the	0
development	0
of	0
hypertension	3
and	0
renal	3
injury	4
in	0
male	0
DS	0
rats	0
on	0
HS	0
diet	0
possibly	0
through	0
upregulation	0
of	0
the	0
intrarenal	0
renin	0
-	0
angiotensin	1
system	0
.	0
Explicit	0
episodic	0
memory	0
for	0
sensory	0
-	0
discriminative	0
components	0
of	0
capsaicin	1
-	0
induced	0
pain	3
:	0
immediate	0
and	0
delayed	0
ratings	0
.	0
Pain	3
memory	0
is	0
thought	0
to	0
affect	0
future	0
pain	3
sensitivity	0
and	0
thus	0
contribute	0
to	0
clinical	0
pain	3
conditions	0
.	0
Systematic	0
investigations	0
of	0
the	0
human	0
capacity	0
to	0
remember	0
sensory	0
features	0
of	0
experimental	0
pain	3
are	0
sparse	0
.	0
In	0
order	0
to	0
address	0
long	0
-	0
term	0
pain	3
memory	0
","	0
nine	0
healthy	0
male	0
volunteers	0
received	0
intradermal	0
injections	0
of	0
three	0
doses	0
of	0
capsaicin	1
(	0
0	0
.	0
5	0
","	0
1	0
and	0
20	0
microg	0
","	0
separated	0
by	0
15	0
min	0
breaks	0
)	0
","	0
each	0
given	0
three	0
times	0
in	0
a	0
balanced	0
design	0
across	0
three	0
sessions	0
at	0
one	0
week	0
intervals	0
.	0
Pain	3
rating	0
was	0
performed	0
using	0
a	0
computerized	0
visual	0
analogue	0
scale	0
(	0
0	0
-	0
100	0
)	0
digitized	0
at	0
1	0
/	0
s	0
","	0
either	0
immediately	0
online	0
or	0
one	0
hour	0
or	0
one	0
day	0
after	0
injection	0
.	0
Subjects	0
also	0
recalled	0
their	0
pains	3
one	0
week	0
later	0
.	0
Capsaicin	1
injection	0
reliably	0
induced	0
a	0
dose	0
-	0
dependent	0
flare	0
(	0
p	0
<	0
0	0
.	0
1	0
)	0
without	0
any	0
difference	0
within	0
or	0
across	0
sessions	0
.	0
The	0
strong	0
burning	0
pain	3
decayed	0
exponentially	0
within	0
a	0
few	0
minutes	0
.	0
Subjects	0
were	0
able	0
to	0
reliably	0
discriminate	0
pain	3
magnitude	0
and	0
duration	0
across	0
capsaicin	1
doses	0
(	0
both	0
p	0
<	0
0	0
.	0
1	0
)	0
","	0
regardless	0
of	0
whether	0
first	0
-	0
time	0
ratings	0
were	0
requested	0
immediately	0
","	0
after	0
one	0
hour	0
or	0
after	0
one	0
day	0
.	0
Pain	3
recall	0
after	0
one	0
week	0
was	0
similarly	0
precise	0
(	0
magnitude	0
:	0
p	0
<	0
0	0
.	0
1	0
","	0
duration	0
:	0
p	0
<	0
0	0
.	0
5	0
)	0
.	0
Correlation	0
with	0
rating	0
recall	0
after	0
one	0
week	0
was	0
best	0
when	0
first	0
-	0
time	0
ratings	0
were	0
requested	0
as	0
late	0
as	0
one	0
day	0
after	0
injection	0
(	0
R	0
(	0
2	0
)	0
=	0
0	0
.	0
79	0
)	0
indicating	0
that	0
both	0
rating	0
retrievals	0
utilized	0
similar	0
memory	0
traces	0
.	0
These	0
results	0
indicate	0
a	0
reliable	0
memory	0
for	0
magnitude	0
and	0
duration	0
of	0
experimentally	0
induced	0
pain	3
.	0
The	0
data	0
further	0
suggest	0
that	0
the	0
consolidation	0
of	0
this	0
memory	0
is	0
an	0
important	0
interim	0
stage	0
","	0
and	0
may	0
take	0
up	0
to	0
one	0
day	0
.	0
Severe	0
and	0
long	0
lasting	0
cholestasis	3
after	0
high	0
-	0
dose	0
co	1
-	2
trimoxazole	2
treatment	0
for	0
Pneumocystis	3
pneumonia	4
in	0
HIV	3
-	4
infected	4
patients	0
-	0
-	0
a	0
report	0
of	0
two	0
cases	0
.	0
Pneumocystis	3
pneumonia	4
(	0
PCP	3
)	0
","	0
a	0
common	0
opportunistic	3
infection	4
in	0
HIV	3
-	4
infected	4
individuals	0
","	0
is	0
generally	0
treated	0
with	0
high	0
doses	0
of	0
co	1
-	2
trimoxazole	2
.	0
However	0
","	0
treatment	0
is	0
often	0
limited	0
by	0
adverse	0
effects	0
.	0
Here	0
","	0
we	0
report	0
two	0
cases	0
of	0
severely	0
immunocompromised	0
HIV	3
-	4
infected	4
patients	0
who	0
developed	0
severe	0
intrahepatic	3
cholestasis	4
","	0
and	0
in	0
one	0
patient	0
lesions	0
mimicking	0
liver	3
abscess	4
formation	0
on	0
radiologic	0
exams	0
","	0
during	0
co	1
-	2
trimoxazole	2
treatment	0
for	0
PCP	3
.	0
Whereas	0
patient	0
1	0
showed	0
lesions	0
of	0
up	0
to	0
1	0
cm	0
readily	0
detectable	0
on	0
magnetic	0
resonance	0
imaging	0
under	0
prolonged	0
co	1
-	2
trimoxazole	2
treatment	0
","	0
therapy	0
of	0
patient	0
2	0
was	0
switched	0
early	0
.	0
Bradykinin	1
receptors	0
antagonists	0
and	0
nitric	1
oxide	2
synthase	0
inhibitors	0
in	0
vincristine	1
and	0
streptozotocin	1
induced	0
hyperalgesia	3
in	0
chemotherapy	0
and	0
diabetic	3
neuropathy	4
rat	0
model	0
.	0
PURP0SE	0
:	0
The	0
influence	0
of	0
an	0
irreversible	0
inhibitor	0
of	0
constitutive	0
N0	1
synthase	0
(	0
L	0
-	0
N0Arg	0
;	0
1	0
.	0
0	0
mg	0
/	0
kg	0
ip	0
)	0
","	0
a	0
relatively	0
selective	0
inhibitor	0
of	0
inducible	0
N0	1
synthase	0
(	0
L	0
-	0
NIL	0
;	0
1	0
.	0
0	0
mg	0
/	0
kg	0
ip	0
)	0
and	0
a	0
relatively	0
specific	0
inhibitor	0
of	0
neuronal	0
N0	1
synthase	0
(	0
7	0
-	0
NI	0
;	0
0	0
.	0
1	0
mg	0
/	0
kg	0
ip	0
)	0
","	0
on	0
antihyperalgesic	0
action	0
of	0
selective	0
antagonists	0
of	0
B2	0
and	0
B1	0
receptors	0
:	0
D	0
-	0
Arg	0
-	0
[	0
Hyp3	0
","	0
Thi5	0
","	0
D	0
-	0
Tic7	0
","	0
0ic8	0
]	0
bradykinin	1
(	0
H0E	1
140	2
;	0
70	0
nmol	0
/	0
kg	0
ip	0
)	0
or	0
des	1
Arg10	2
H0E	2
140	2
(	0
70	0
nmol	0
/	0
kg	0
ip	0
)	0
respectively	0
","	0
in	0
model	0
of	0
diabetic	3
(	4
streptozotocin	4
-	4
induced	4
)	4
and	4
toxic	4
(	4
vincristine	4
-	4
induced	4
)	4
neuropathy	4
was	0
investigated	0
.	0
METH0DS	0
:	0
The	0
changes	0
in	0
pain	3
thresholds	0
were	0
determined	0
using	0
mechanical	0
stimuli	0
-	0
-	0
the	0
modification	0
of	0
the	0
classic	0
paw	0
withdrawal	0
test	0
described	0
by	0
Randall	0
-	0
Selitto	0
.	0
RESULTS	0
:	0
The	0
results	0
of	0
this	0
paper	0
confirm	0
that	0
inhibition	0
of	0
bradykinin	1
receptors	0
and	0
inducible	0
N0	1
synthase	0
but	0
not	0
neuronal	0
N0	1
synthase	0
activity	0
reduces	0
diabetic	3
hyperalgesia	4
.	0
Pretreatment	0
with	0
L	0
-	0
N0Arg	0
and	0
L	0
-	0
NIL	0
but	0
not	0
7	0
-	0
NI	0
","	0
significantly	0
increases	0
antihyperalgesic	0
activity	0
both	0
H0E	1
140	2
and	0
des	1
Arg10	2
H0E	2
140	2
.	0
It	0
was	0
also	0
shown	0
that	0
both	0
products	0
of	0
inducible	0
N0	1
synthase	0
and	0
neuronal	0
N0	1
synthase	0
activation	0
as	0
well	0
as	0
bradykinin	1
are	0
involved	0
in	0
hyperalgesia	3
produced	0
by	0
vincristine	1
.	0
Moreover	0
","	0
L	0
-	0
N0Arg	0
and	0
7	0
-	0
NI	0
but	0
not	0
L	0
-	0
NIL	0
intensify	0
antihyperalgesic	0
activity	0
of	0
H0E	1
140	2
or	0
des	1
-	2
Arg10H0E	2
140	2
in	0
toxic	3
neuropathy	4
.	0
C0NCLUSI0NS	0
:	0
Results	0
of	0
these	0
studies	0
suggest	0
that	0
B1	0
and	0
B2	0
receptors	0
are	0
engaged	0
in	0
transmission	0
of	0
nociceptive	0
stimuli	0
in	0
both	0
diabetic	3
and	4
toxic	4
neuropathy	4
.	0
In	0
streptozotocin	1
-	0
induced	0
hyperalgesia	3
","	0
inducible	0
N0	1
synthase	0
participates	0
in	0
pronociceptive	0
activity	0
of	0
bradykinin	1
","	0
whereas	0
in	0
vincristine	1
-	0
induced	0
hyperalgesia	3
bradykinin	1
seemed	0
to	0
activate	0
neuronal	0
N0	1
synthase	0
pathway	0
.	0
Therefore	0
","	0
concomitant	0
administration	0
of	0
small	0
doses	0
of	0
bradykinin	1
receptor	0
antagonists	0
and	0
N0	1
synthase	0
inhibitors	0
can	0
be	0
effective	0
in	0
alleviation	0
of	0
neuropathic	3
pain	4
","	0
even	0
in	0
hospital	0
care	0
.	0
Confusion	3
","	0
a	0
rather	0
serious	0
adverse	0
drug	0
reaction	0
with	0
valproic	1
acid	2
:	0
a	0
review	0
of	0
the	0
French	0
Pharmacovigilance	0
database	0
.	0
INTR0DUCTI0N	0
:	0
Confusion	3
is	0
an	0
adverse	0
drug	0
reaction	0
frequently	0
observed	0
with	0
valproic	1
acid	2
.	0
Some	0
case	0
reports	0
are	0
published	0
in	0
the	0
literature	0
but	0
no	0
systematic	0
study	0
from	0
a	0
sample	0
of	0
patients	0
has	0
been	0
published	0
.	0
We	0
performed	0
this	0
study	0
in	0
order	0
to	0
describe	0
the	0
main	0
characteristics	0
of	0
this	0
adverse	0
drug	0
reaction	0
.	0
METH0DS	0
:	0
Using	0
the	0
French	0
Pharmacovigilance	0
database	0
","	0
we	0
selected	0
the	0
cases	0
of	0
confusion	3
reported	0
since	0
1985	0
with	0
valproic	1
acid	2
.	0
RESULTS	0
:	0
272	0
cases	0
of	0
confusion	3
were	0
reported	0
with	0
valproic	1
acid	2
:	0
153	0
women	0
and	0
119	0
men	0
.	0
Confusion	3
mostly	0
occurred	0
during	0
the	0
two	0
first	0
weeks	0
following	0
valproic	1
acid	2
exposure	0
(	0
39	0
.	0
7	0
%	0
)	0
.	0
It	0
was	0
"	0
serious	0
"	0
for	0
almost	0
2	0
/	0
3	0
of	0
the	0
patients	0
(	0
62	0
.	0
5	0
%	0
)	0
and	0
its	0
outcome	0
favourable	0
in	0
most	0
of	0
the	0
cases	0
(	0
82	0
%	0
)	0
.	0
The	0
occurrence	0
of	0
this	0
ADR	0
was	0
more	0
frequent	0
in	0
patients	0
aged	0
between	0
61	0
and	0
80	0
years	0
.	0
C0NCLUSI0N	0
:	0
This	0
work	0
shows	0
that	0
confusion	3
with	0
valproic	1
acid	2
is	0
a	0
serious	0
","	0
rather	0
frequent	0
but	0
reversible	0
adverse	0
drug	0
reaction	0
.	0
It	0
occurs	0
especially	0
in	0
older	0
patients	0
and	0
during	0
the	0
first	0
two	0
weeks	0
of	0
treatment	0
.	0
Reversible	0
inferior	3
colliculus	4
lesion	4
in	0
metronidazole	1
-	0
induced	0
encephalopathy	3
:	0
magnetic	0
resonance	0
findings	0
on	0
diffusion	0
-	0
weighted	0
and	0
fluid	0
attenuated	0
inversion	0
recovery	0
imaging	0
.	0
0BJECTIVE	0
:	0
This	0
is	0
to	0
present	0
reversible	0
inferior	3
colliculus	4
lesions	4
in	0
metronidazole	1
-	0
induced	0
encephalopathy	3
","	0
to	0
focus	0
on	0
the	0
diffusion	0
-	0
weighted	0
imaging	0
(	0
DWI	0
)	0
and	0
fluid	0
attenuated	0
inversion	0
recovery	0
(	0
FLAIR	0
)	0
imaging	0
.	0
MATERIALS	0
AND	0
METH0DS	0
:	0
From	0
November	0
2005	0
to	0
September	0
2007	0
","	0
8	0
patients	0
(	0
5	0
men	0
and	0
3	0
women	0
)	0
were	0
diagnosed	0
as	0
having	0
metronidazole	1
-	0
induced	0
encephalopathy	3
(	0
age	0
range	0
;	0
43	0
-	0
78	0
years	0
)	0
.	0
They	0
had	0
been	0
taking	0
metronidazole	1
(	0
total	0
dosage	0
","	0
45	0
-	0
120	0
g	0
;	0
duration	0
","	0
30	0
days	0
to	0
2	0
months	0
)	0
to	0
treat	0
the	0
infection	3
in	0
various	0
organs	0
.	0
Initial	0
brain	0
magnetic	0
resonance	0
imaging	0
(	0
MRI	0
)	0
were	0
obtained	0
after	0
the	0
hospitalization	0
","	0
including	0
DWI	0
(	0
8	0
/	0
8	0
)	0
","	0
apparent	0
diffusion	0
coefficient	0
(	0
ADC	0
)	0
map	0
(	0
4	0
/	0
8	0
)	0
","	0
FLAIR	0
(	0
7	0
/	0
8	0
)	0
","	0
and	0
T2	0
-	0
weighted	0
image	0
(	0
8	0
/	0
8	0
)	0
.	0
Follow	0
-	0
up	0
MRIs	0
were	0
performed	0
on	0
5	0
patients	0
from	0
third	0
to	0
14th	0
days	0
after	0
discontinuation	0
of	0
metronidazole	1
administration	0
.	0
Findings	0
of	0
initial	0
and	0
follow	0
-	0
up	0
MRIs	0
were	0
retrospectively	0
evaluated	0
by	0
2	0
neuroradiologists	0
by	0
consensus	0
","	0
to	0
analyze	0
the	0
presence	0
of	0
abnormal	0
signal	0
intensities	0
","	0
their	0
locations	0
","	0
and	0
signal	0
changes	0
on	0
follow	0
-	0
up	0
images	0
.	0
RESULTS	0
:	0
Initial	0
MRIs	0
showed	0
abnormal	0
high	0
signal	0
intensities	0
on	0
DWI	0
and	0
FLAIR	0
(	0
or	0
T2	0
-	0
weighted	0
image	0
)	0
at	0
the	0
dentate	0
nucleus	0
(	0
8	0
/	0
8	0
)	0
","	0
inferior	0
colliculus	0
(	0
6	0
/	0
8	0
)	0
","	0
corpus	0
callosum	0
(	0
2	0
/	0
8	0
)	0
","	0
pons	0
(	0
2	0
/	0
8	0
)	0
","	0
medulla	0
(	0
1	0
/	0
8	0
)	0
","	0
and	0
bilateral	0
cerebral	0
white	0
matter	0
(	0
1	0
/	0
8	0
)	0
.	0
High	0
-	0
signal	0
intensity	0
lesions	0
on	0
DWI	0
tended	0
to	0
show	0
low	0
signal	0
intensity	0
on	0
ADC	0
map	0
(	0
3	0
/	0
4	0
)	0
","	0
but	0
in	0
one	0
patient	0
","	0
high	0
signal	0
intensity	0
was	0
shown	0
at	0
bilateral	0
dentate	0
nuclei	0
on	0
not	0
only	0
DWI	0
but	0
also	0
ADC	0
map	0
.	0
All	0
the	0
lesions	0
in	0
dentate	0
","	0
inferior	0
colliculus	0
","	0
pons	0
","	0
and	0
medullas	0
had	0
been	0
resolved	0
completely	0
on	0
follow	0
-	0
up	0
MRIs	0
in	0
5	0
patients	0
","	0
but	0
in	0
1	0
patient	0
of	0
them	0
","	0
corpus	0
callosal	3
lesion	4
persisted	0
.	0
C0NCLUSI0NS	0
:	0
Reversible	0
inferior	3
colliculus	4
lesions	4
could	0
be	0
considered	0
as	0
the	0
characteristic	0
for	0
metronidazole	1
-	0
induced	0
encephalopathy	3
","	0
next	0
to	0
the	0
dentate	0
nucleus	0
involvement	0
.	0
Clinically	0
significant	0
proteinuria	3
following	0
the	0
administration	0
of	0
sirolimus	1
to	0
renal	0
transplant	0
recipients	0
.	0
BACKGR0UND	0
:	0
Sirolimus	1
is	0
the	0
latest	0
immunosuppressive	0
agent	0
used	0
to	0
prevent	0
rejection	0
","	0
and	0
may	0
have	0
less	0
nephrotoxicity	3
than	0
calcineurin	0
inhibitor	0
(	0
CNI	0
)	0
-	0
based	0
regimens	0
.	0
To	0
date	0
there	0
has	0
been	0
little	0
documentation	0
of	0
clinically	0
significant	0
proteinuria	3
linked	0
with	0
the	0
use	0
of	0
sirolimus	1
.	0
We	0
have	0
encountered	0
several	0
patients	0
who	0
developed	0
substantial	0
proteinuria	3
associated	0
with	0
sirolimus	1
use	0
.	0
In	0
each	0
patient	0
","	0
the	0
close	0
temporal	0
association	0
between	0
the	0
commencement	0
of	0
sirolimus	1
therapy	0
and	0
proteinuria	3
implicated	0
sirolimus	1
as	0
the	0
most	0
likely	0
etiology	0
of	0
the	0
proteinuria	3
.	0
METH0DS	0
:	0
We	0
analyzed	0
the	0
clinical	0
and	0
laboratory	0
information	0
available	0
for	0
all	0
119	0
patients	0
transplanted	0
at	0
the	0
Washington	0
Hospital	0
Center	0
between	0
1999	0
-	0
2003	0
for	0
whom	0
sirolimus	1
was	0
a	0
component	0
of	0
their	0
immunosuppressant	0
regimen	0
.	0
In	0
these	0
patients	0
","	0
the	0
magnitude	0
of	0
proteinuria	3
was	0
assessed	0
on	0
morning	0
urine	0
samples	0
by	0
turbidometric	0
measurement	0
or	0
random	0
urine	0
protein	0
:	0
creatinine	1
ratios	0
","	0
an	0
estimate	0
of	0
grams	0
of	0
proteinuria	3
/	0
day	0
.	0
Laboratory	0
results	0
were	0
compared	0
between	0
prior	0
","	0
during	0
and	0
following	0
sirolimus	1
use	0
.	0
RESULTS	0
:	0
Twenty	0
-	0
eight	0
patients	0
(	0
24	0
%	0
)	0
developed	0
increased	0
proteinuria	3
from	0
baseline	0
during	0
their	0
post	0
-	0
transplantation	0
course	0
.	0
In	0
21	0
patients	0
an	0
alternative	0
cause	0
of	0
proteinuria	3
was	0
either	0
obvious	0
or	0
insufficient	0
data	0
was	0
available	0
to	0
be	0
conclusive	0
.	0
In	0
7	0
of	0
the	0
28	0
patients	0
there	0
was	0
a	0
striking	0
temporal	0
association	0
between	0
the	0
initiation	0
of	0
sirolimus	1
and	0
the	0
development	0
of	0
nephrotic	3
-	0
range	0
proteinuria	3
.	0
Proteinuria	3
correlated	0
most	0
strongly	0
with	0
sirolimus	1
therapy	0
when	0
compared	0
to	0
other	0
demographic	0
and	0
clinical	0
variables	0
.	0
In	0
most	0
patients	0
","	0
discontinuation	0
of	0
sirolimus	1
resulted	0
in	0
a	0
decrease	0
","	0
but	0
not	0
resolution	0
","	0
of	0
proteinuria	3
.	0
C0NCLUSI0NS	0
:	0
Sirolimus	1
induces	0
or	0
aggravates	0
pre	0
-	0
existing	0
proteinuria	3
in	0
an	0
unpredictable	0
subset	0
of	0
renal	0
allograft	0
recipients	0
.	0
Proteinuria	3
may	0
improve	0
","	0
but	0
does	0
not	0
resolve	0
","	0
when	0
sirolimus	1
is	0
withdrawn	0
.	0
Components	0
of	0
lemon	0
essential	0
oil	0
attenuate	0
dementia	3
induced	0
by	0
scopolamine	1
.	0
The	0
anti	0
-	0
dementia	3
effects	0
of	0
s	1
-	2
limonene	2
and	0
s	1
-	2
perillyl	2
alcohol	2
were	0
observed	0
using	0
the	0
passive	0
avoidance	0
test	0
(	0
PA	0
)	0
and	0
the	0
open	0
field	0
habituation	0
test	0
(	0
0FH	0
)	0
.	0
These	0
lemon	0
essential	0
oils	0
showed	0
strong	0
ability	0
to	0
improve	0
memory	3
impaired	4
by	0
scopolamine	1
;	0
however	0
","	0
s	1
-	2
perillyl	2
alcohol	2
relieved	0
the	0
deficit	3
of	4
associative	4
memory	4
in	0
PA	0
only	0
","	0
and	0
did	0
not	0
improve	0
non	0
-	0
associative	0
memory	0
significantly	0
in	0
0FH	0
.	0
Analysis	0
of	0
neurotransmitter	0
concentration	0
in	0
some	0
brain	0
regions	0
on	0
the	0
test	0
day	0
showed	0
that	0
dopamine	1
concentration	0
of	0
the	0
vehicle	0
/	0
scopolamine	1
group	0
was	0
significantly	0
lower	0
than	0
that	0
of	0
the	0
vehicle	0
/	0
vehicle	0
group	0
","	0
but	0
this	0
phenomenon	0
was	0
reversed	0
when	0
s	1
-	2
limonene	2
or	0
s	1
-	2
perillyl	2
alcohol	2
were	0
administered	0
before	0
the	0
injection	0
of	0
scopolamine	1
.	0
Simultaneously	0
","	0
we	0
found	0
that	0
these	0
two	0
lemon	0
essential	0
oil	0
components	0
could	0
inhibit	0
acetylcholinesterase	0
activity	0
in	0
vitro	0
using	0
the	0
Ellman	0
method	0
.	0
Attentional	0
modulation	0
of	0
perceived	0
pain	3
intensity	0
in	0
capsaicin	1
-	0
induced	0
secondary	0
hyperalgesia	3
.	0
Perceived	0
pain	3
intensity	0
is	0
modulated	0
by	0
attention	0
.	0
However	0
","	0
it	0
is	0
not	0
known	0
that	0
how	0
pain	3
intensity	0
ratings	0
are	0
affected	0
by	0
attention	0
in	0
capsaicin	1
-	0
induced	0
secondary	0
hyperalgesia	3
.	0
Here	0
we	0
show	0
that	0
perceived	0
pain	3
intensity	0
in	0
secondary	0
hyperalgesia	3
is	0
decreased	0
when	0
attention	0
is	0
distracted	0
away	0
from	0
the	0
painful	0
pinprick	0
stimulus	0
with	0
a	0
visual	0
task	0
.	0
Furthermore	0
","	0
it	0
was	0
found	0
that	0
the	0
magnitude	0
of	0
attentional	0
modulation	0
in	0
secondary	0
hyperalgesia	3
is	0
very	0
similar	0
to	0
that	0
of	0
capsaicin	1
-	0
untreated	0
","	0
control	0
condition	0
.	0
0ur	0
findings	0
","	0
showing	0
no	0
interaction	0
between	0
capsaicin	1
treatment	0
and	0
attentional	0
modulation	0
suggest	0
that	0
capsaicin	1
-	0
induced	0
secondary	0
hyperalgesia	3
and	0
attention	0
might	0
affect	0
mechanical	0
pain	3
through	0
independent	0
mechanisms	0
.	0
Cardioprotective	0
effect	0
of	0
salvianolic	1
acid	2
A	2
on	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
in	0
rats	0
.	0
The	0
present	0
study	0
was	0
designed	0
to	0
evaluate	0
the	0
cardioprotective	0
potential	0
of	0
salvianolic	1
acid	2
A	2
on	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
in	0
rats	0
.	0
Hemodynamic	0
parameters	0
and	0
lead	0
II	0
electrocardiograph	0
were	0
monitored	0
and	0
recorded	0
continuously	0
.	0
Cardiac	0
marker	0
enzymes	0
and	0
antioxidative	0
parameters	0
in	0
serum	0
and	0
heart	0
tissues	0
were	0
measured	0
.	0
Assay	0
for	0
mitochondrial	0
respiratory	0
function	0
and	0
histopathological	0
examination	0
of	0
heart	0
tissues	0
were	0
performed	0
.	0
Isoproterenol	1
-	0
treated	0
rats	0
showed	0
significant	0
increases	0
in	0
the	0
levels	0
of	0
lactate	1
dehydrogenase	0
","	0
aspartate	1
transaminase	0
","	0
creatine	1
kinase	0
and	0
malondialdehyde	1
and	0
significant	0
decreases	0
in	0
the	0
activities	0
of	0
superoxide	1
dismutase	0
","	0
catalase	0
and	0
glutathione	1
peroxidase	0
in	0
serum	0
and	0
heart	0
.	0
These	0
rats	0
also	0
showed	0
declines	0
in	0
left	0
ventricular	0
systolic	0
pressure	0
","	0
maximum	0
and	0
minimum	0
rate	0
of	0
developed	0
left	0
ventricular	0
pressure	0
","	0
and	0
elevation	0
of	0
left	0
ventricular	0
end	0
-	0
diastolic	0
pressure	0
and	0
ST	0
-	0
segment	0
.	0
In	0
addition	0
","	0
mitochondrial	0
respiratory	3
dysfunction	4
characterized	0
by	0
decreased	0
respiratory	0
control	0
ratio	0
and	0
ADP	1
/	0
0	0
was	0
observed	0
in	0
isoproterenol	1
-	0
treated	0
rats	0
.	0
Administration	0
of	0
salvianolic	1
acid	2
A	2
for	0
a	0
period	0
of	0
8	0
days	0
significantly	0
attenuated	0
isoproterenol	1
-	0
induced	0
cardiac	3
dysfunction	4
and	0
myocardial	3
injury	4
and	0
improved	0
mitochondrial	0
respiratory	0
function	0
.	0
The	0
protective	0
role	0
of	0
salvianolic	1
acid	2
A	2
against	0
isoproterenol	1
-	0
induced	0
myocardial	3
damage	4
was	0
further	0
confirmed	0
by	0
histopathological	0
examination	0
.	0
The	0
results	0
of	0
our	0
study	0
suggest	0
that	0
salvianolic	1
acid	2
A	2
possessing	0
antioxidant	0
activity	0
has	0
a	0
significant	0
protective	0
effect	0
against	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
.	0
Long	0
-	0
term	0
glutamate	1
supplementation	0
failed	0
to	0
protect	0
against	0
peripheral	3
neurotoxicity	4
of	0
paclitaxel	1
.	0
Toxic	0
peripheral	3
neuropathy	4
is	0
still	0
a	0
significant	0
limiting	0
factor	0
for	0
chemotherapy	0
with	0
paclitaxel	1
(	0
PAC	1
)	0
","	0
although	0
glutamate	1
and	0
its	0
closely	0
related	0
amino	1
acid	2
glutamine	1
were	0
claimed	0
to	0
ameliorate	0
PAC	1
neurotoxicity	3
.	0
This	0
pilot	0
trial	0
aimed	0
to	0
evaluate	0
the	0
role	0
of	0
glutamate	1
supplementation	0
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801	2
)	0
or	0
transgenic	0
mice	0
(	0
ie	0
","	0
NMDA	1
Nr1	0
(	0
neo	0
-	0
/	0
-	0
)	0
and	0
DAT	0
(	0
-	0
/	0
-	0
)	0
)	0
.	0
Results	0
showed	0
that	0
SSR103800	1
(	0
10	0
-	0
30	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
)	0
blocked	0
hyperactivity	3
induced	0
by	0
the	0
non	0
-	0
competitive	0
NMDA	1
receptor	0
antagonist	0
","	0
MK	1
-	2
801	2
and	0
partially	0
reversed	0
spontaneous	0
hyperactivity	3
of	0
NMDA	1
Nr1	0
(	0
neo	0
-	0
/	0
-	0
)	0
mice	0
.	0
In	0
contrast	0
","	0
SSR103800	1
failed	0
to	0
affect	0
hyperactivity	3
induced	0
by	0
amphetamine	1
or	0
naturally	0
observed	0
in	0
dopamine	1
transporter	0
(	0
DAT	0
(	0
-	0
/	0
-	0
)	0
)	0
knockout	0
mice	0
(	0
10	0
-	0
30	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
)	0
.	0
Importantly	0
","	0
both	0
classical	0
(	0
haloperidol	1
)	0
and	0
atypical	0
(	0
olanzapine	1
","	0
clozapine	1
and	0
aripiprazole	1
)	0
antipsychotics	0
were	0
effective	0
in	0
all	0
these	0
models	0
of	0
hyperactivity	3
.	0
However	0
","	0
unlike	0
these	0
latter	0
","	0
SSR103800	1
did	0
not	0
produce	0
catalepsy	3
(	0
retention	0
on	0
the	0
bar	0
test	0
)	0
up	0
to	0
30	0
mg	0
/	0
kg	0
p	0
.	0
o	0
.	0
Together	0
these	0
findings	0
show	0
that	0
the	0
GlyT1	0
inhibitor	0
","	0
SSR103800	1
","	0
produces	0
antipsychotic	0
-	0
like	0
effects	0
","	0
which	0
differ	0
from	0
those	0
observed	0
with	0
compounds	0
primarily	0
targeting	0
the	0
dopaminergic	0
system	0
","	0
and	0
has	0
a	0
reduced	0
side	0
-	0
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potential	0
as	0
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these	0
latter	0
drugs	0
.	0
Pyrrolidine	1
dithiocarbamate	2
protects	0
the	0
piriform	0
cortex	0
in	0
the	0
pilocarpine	1
status	3
epilepticus	4
model	0
.	0
Pyrrolidine	1
dithiocarbamate	2
(	0
PDTC	1
)	0
has	0
a	0
dual	0
mechanism	0
of	0
action	0
as	0
an	0
antioxidant	0
and	0
an	0
inhibitor	0
of	0
the	0
transcription	0
factor	0
kappa	0
-	0
beta	0
.	0
Both	0
","	0
production	0
of	0
reactive	0
oxygen	1
species	0
as	0
well	0
as	0
activation	0
of	0
NF	0
-	0
kappaB	0
have	0
been	0
implicated	0
in	0
severe	0
neuronal	3
damage	4
in	0
different	0
sub	0
-	0
regions	0
of	0
the	0
hippocampus	0
as	0
well	0
as	0
in	0
the	0
surrounding	0
cortices	0
.	0
The	0
effect	0
of	0
PDTC	1
on	0
status	3
epilepticus	4
-	0
associated	0
cell	0
loss	0
in	0
the	0
hippocampus	0
and	0
piriform	0
cortex	0
was	0
evaluated	0
in	0
the	0
rat	0
fractionated	0
pilocarpine	1
model	0
.	0
Treatment	0
with	0
150	0
mg	0
/	0
kg	0
PDTC	1
before	0
and	0
following	0
status	3
epilepticus	4
significantly	0
increased	0
the	0
mortality	0
rate	0
to	0
100	0
%	0
.	0
Administration	0
of	0
50	0
mg	0
/	0
kg	0
PDTC	1
(	0
low	0
-	0
dose	0
)	0
did	0
not	0
exert	0
major	0
effects	0
on	0
the	0
development	0
of	0
a	0
status	3
epilepticus	4
or	0
the	0
mortality	0
rate	0
.	0
In	0
vehicle	0
-	0
treated	0
rats	0
","	0
status	3
epilepticus	4
caused	0
pronounced	0
neuronal	3
damage	4
in	0
the	0
piriform	0
cortex	0
comprising	0
both	0
pyramidal	0
cells	0
and	0
interneurons	0
.	0
Low	0
-	0
dose	0
PDTC	1
treatment	0
almost	0
completely	0
protected	0
from	0
lesions	0
in	0
the	0
piriform	0
cortex	0
.	0
A	0
significant	0
decrease	0
in	0
neuronal	0
density	0
of	0
the	0
hippocampal	0
hilar	0
formation	0
was	0
identified	0
in	0
vehicle	0
-	0
and	0
PDTC	1
-	0
treated	0
rats	0
following	0
status	3
epilepticus	4
.	0
In	0
conclusion	0
","	0
the	0
NF	0
-	0
kappaB	0
inhibitor	0
and	0
antioxidant	0
PDTC	1
protected	0
the	0
piriform	0
cortex	0
","	0
whereas	0
it	0
did	0
not	0
affect	0
hilar	0
neuronal	3
loss	4
.	0
These	0
data	0
might	0
indicate	0
that	0
the	0
generation	0
of	0
reactive	0
oxygen	1
species	0
and	0
activation	0
of	0
NF	0
-	0
kappaB	0
plays	0
a	0
more	0
central	0
role	0
in	0
seizure	3
-	0
associated	0
neuronal	3
damage	4
in	0
the	0
temporal	0
cortex	0
as	0
compared	0
to	0
the	0
hippocampal	0
hilus	0
.	0
However	0
","	0
future	0
investigations	0
are	0
necessary	0
to	0
exactly	0
analyze	0
the	0
biochemical	0
mechanisms	0
by	0
which	0
PDTC	1
exerted	0
its	0
beneficial	0
effects	0
in	0
the	0
piriform	0
cortex	0
.	0
Anaesthetists	0
'	0
nightmare	0
:	0
masseter	3
spasm	4
after	0
induction	0
in	0
an	0
undiagnosed	0
case	0
of	0
myotonia	3
congenita	4
.	0
We	0
report	0
an	0
undiagnosed	0
case	0
of	0
myotonia	3
congenita	4
in	0
a	0
24	0
-	0
year	0
-	0
old	0
previously	0
healthy	0
primigravida	0
","	0
who	0
developed	0
life	0
threatening	0
masseter	3
spasm	4
following	0
a	0
standard	0
dose	0
of	0
intravenous	0
suxamethonium	1
for	0
induction	0
of	0
anaesthesia	0
.	0
Neither	0
the	0
patient	0
nor	0
the	0
anaesthetist	0
was	0
aware	0
of	0
the	0
diagnosis	0
before	0
this	0
potentially	0
lethal	0
complication	0
occurred	0
.	0
Twin	0
preterm	0
neonates	0
with	0
cardiac	3
toxicity	4
related	0
to	0
lopinavir	1
/	2
ritonavir	2
therapy	0
.	0
We	0
report	0
twin	0
neonates	0
who	0
were	0
born	0
prematurely	0
at	0
32	0
weeks	0
of	0
gestation	0
to	0
a	0
mother	0
with	0
human	3
immunodeficiency	4
virus	4
infection	4
.	0
0ne	0
of	0
the	0
twins	0
developed	0
complete	0
heart	3
block	4
and	0
dilated	3
cardiomyopathy	4
related	0
to	0
lopinavir	1
/	2
ritonavir	2
therapy	0
","	0
a	0
boosted	0
protease	0
-	0
inhibitor	0
agent	0
","	0
while	0
the	0
other	0
twin	0
developed	0
mild	0
bradycardia	3
.	0
We	0
recommend	0
caution	0
in	0
the	0
use	0
of	0
lopinavir	1
/	2
ritonavir	2
in	0
the	0
immediate	0
neonatal	0
period	0
.	0
When	0
drugs	0
disappear	0
from	0
the	0
patient	0
:	0
elimination	0
of	0
intravenous	0
medication	0
by	0
hemodiafiltration	0
.	0
Twenty	0
-	0
three	0
hours	0
after	0
heart	0
transplantation	0
","	0
life	0
-	0
threatening	0
acute	0
right	3
heart	4
failure	4
was	0
diagnosed	0
in	0
a	0
patient	0
requiring	0
continuous	0
venovenous	0
hemodiafiltration	0
(	0
CVVHDF	0
)	0
.	0
Increasing	0
doses	0
of	0
catecholamines	1
","	0
sedatives	0
","	0
and	0
muscle	0
relaxants	0
administered	0
through	0
a	0
central	0
venous	0
catheter	0
were	0
ineffective	0
.	0
However	0
","	0
a	0
bolus	0
of	0
epinephrine	1
injected	0
through	0
an	0
alternative	0
catheter	0
provoked	0
a	0
hypertensive	3
crisis	0
.	0
Thus	0
","	0
interference	0
with	0
the	0
central	0
venous	0
infusion	0
by	0
the	0
dialysis	0
catheter	0
was	0
suspected	0
.	0
The	0
catheters	0
were	0
changed	0
","	0
and	0
hemodynamics	0
stabilized	0
at	0
lower	0
catecholamine	1
doses	0
.	0
When	0
the	0
effects	0
of	0
IV	0
drugs	0
are	0
inadequate	0
in	0
patients	0
receiving	0
CVVHDF	0
","	0
interference	0
with	0
adjacent	0
catheters	0
resulting	0
in	0
elimination	0
of	0
the	0
drug	0
by	0
CVVHDF	0
should	0
be	0
suspected	0
.	0
Less	0
frequent	0
lithium	1
administration	0
and	0
lower	0
urine	0
volume	0
.	0
0BJECTIVE	0
:	0
This	0
study	0
was	0
designed	0
to	0
determine	0
whether	0
patients	0
maintained	0
on	0
a	0
regimen	0
of	0
lithium	1
on	0
a	0
once	0
-	0
per	0
-	0
day	0
schedule	0
have	0
lower	0
urine	0
volumes	0
than	0
do	0
patients	0
receiving	0
multiple	0
doses	0
per	0
day	0
.	0
METH0D	0
:	0
This	0
was	0
a	0
cross	0
-	0
sectional	0
study	0
of	0
85	0
patients	0
from	0
a	0
lithium	1
clinic	0
who	0
received	0
different	0
dose	0
schedules	0
.	0
Patients	0
were	0
admitted	0
to	0
the	0
hospital	0
for	0
measurement	0
of	0
lithium	1
level	0
","	0
creatinine	1
clearance	0
","	0
urine	0
volume	0
","	0
and	0
maximum	0
osmolality	0
.	0
RESULTS	0
:	0
Multiple	0
daily	0
doses	0
of	0
lithium	1
were	0
associated	0
with	0
higher	0
urine	0
volumes	0
.	0
The	0
dosing	0
schedule	0
","	0
duration	0
of	0
lithium	1
treatment	0
","	0
and	0
daily	0
dose	0
of	0
lithium	1
did	0
not	0
affect	0
maximum	0
osmolality	0
or	0
creatinine	1
clearance	0
.	0
C0NCLUSI0NS	0
:	0
Urine	0
volume	0
can	0
be	0
reduced	0
by	0
giving	0
lithium	1
once	0
daily	0
and	0
/	0
or	0
by	0
lowering	0
the	0
total	0
daily	0
dose	0
.	0
Lithium	1
-	0
induced	0
polyuria	3
seems	0
to	0
be	0
related	0
to	0
extrarenal	0
as	0
well	0
as	0
to	0
renal	0
effects	0
.	0
Antibacterial	0
medication	0
use	0
during	0
pregnancy	0
and	0
risk	0
of	0
birth	3
defects	4
:	0
National	0
Birth	3
Defects	4
Prevention	0
Study	0
.	0
0BJECTIVE	0
:	0
To	0
estimate	0
the	0
association	0
between	0
antibacterial	0
medications	0
and	0
selected	0
birth	3
defects	4
.	0
DESIGN	0
","	0
SETTING	0
","	0
AND	0
PARTICIPANTS	0
:	0
Population	0
-	0
based	0
","	0
multisite	0
","	0
case	0
-	0
control	0
study	0
of	0
women	0
who	0
had	0
pregnancies	0
affected	0
by	0
1	0
of	0
more	0
than	0
30	0
eligible	0
major	0
birth	3
defects	4
identified	0
via	0
birth	3
defect	4
surveillance	0
programs	0
in	0
10	0
states	0
(	0
n	0
=	0
13	0
155	0
)	0
and	0
control	0
women	0
randomly	0
selected	0
from	0
the	0
same	0
geographical	0
regions	0
(	0
n	0
=	0
4941	0
)	0
.	0
MAIN	0
EXP0SURE	0
:	0
Reported	0
maternal	0
use	0
of	0
antibacterials	0
(	0
1	0
month	0
before	0
pregnancy	0
through	0
the	0
end	0
of	0
the	0
first	0
trimester	0
)	0
.	0
MAIN	0
0UTC0ME	0
MEASURE	0
:	0
0dds	0
ratios	0
(	0
0Rs	0
)	0
measuring	0
the	0
association	0
between	0
antibacterial	0
use	0
and	0
selected	0
birth	3
defects	4
adjusted	0
for	0
potential	0
confounders	0
.	0
RESULTS	0
:	0
The	0
reported	0
use	0
of	0
antibacterials	0
increased	0
during	0
pregnancy	0
","	0
peaking	0
during	0
the	0
third	0
month	0
.	0
Sulfonamides	1
were	0
associated	0
with	0
anencephaly	3
(	0
adjusted	0
0R	0
[	0
A0R	0
]	0
=	0
3	0
.	0
4	0
;	0
95	0
%	0
confidence	0
interval	0
[	0
CI	0
]	0
","	0
1	0
.	0
3	0
-	0
8	0
.	0
8	0
)	0
","	0
hypoplastic	3
left	4
heart	4
syndrome	4
(	0
A0R	0
=	0
3	0
.	0
2	0
;	0
95	0
%	0
CI	0
","	0
1	0
.	0
3	0
-	0
7	0
.	0
6	0
)	0
","	0
coarctation	3
of	4
the	4
aorta	4
(	0
A0R	0
=	0
2	0
.	0
7	0
;	0
95	0
%	0
CI	0
","	0
1	0
.	0
3	0
-	0
5	0
.	0
6	0
)	0
","	0
choanal	3
atresia	4
(	0
A0R	0
=	0
8	0
.	0
0	0
;	0
95	0
%	0
CI	0
","	0
2	0
.	0
7	0
-	0
23	0
.	0
5	0
)	0
","	0
transverse	3
limb	4
deficiency	4
(	0
A0R	0
=	0
2	0
.	0
5	0
;	0
95	0
%	0
CI	0
","	0
1	0
.	0
0	0
-	0
5	0
.	0
9	0
)	0
","	0
and	0
diaphragmatic	3
hernia	4
(	0
A0R	0
=	0
2	0
.	0
4	0
;	0
95	0
%	0
CI	0
","	0
1	0
.	0
1	0
-	0
5	0
.	0
4	0
)	0
.	0
Nitrofurantoins	1
were	0
associated	0
with	0
anophthalmia	3
or	0
microphthalmos	3
(	0
A0R	0
=	0
3	0
.	0
7	0
;	0
95	0
%	0
CI	0
","	0
1	0
.	0
1	0
-	0
12	0
.	0
2	0
)	0
","	0
hypoplastic	3
left	4
heart	4
syndrome	4
(	0
A0R	0
=	0
4	0
.	0
2	0
;	0
95	0
%	0
CI	0
","	0
1	0
.	0
9	0
-	0
9	0
.	0
1	0
)	0
","	0
atrial	3
septal	4
defects	4
(	0
A0R	0
=	0
1	0
.	0
9	0
;	0
95	0
%	0
CI	0
","	0
1	0
.	0
1	0
-	0
3	0
.	0
4	0
)	0
","	0
and	0
cleft	3
lip	4
with	0
cleft	3
palate	4
(	0
A0R	0
=	0
2	0
.	0
1	0
;	0
95	0
%	0
CI	0
","	0
1	0
.	0
2	0
-	0
3	0
.	0
9	0
)	0
.	0
0ther	0
antibacterial	0
agents	0
that	0
showed	0
associations	0
included	0
erythromycins	1
(	0
2	0
defects	0
)	0
","	0
penicillins	1
(	0
1	0
defect	0
)	0
","	0
cephalosporins	1
(	0
1	0
defect	0
)	0
","	0
and	0
quinolones	1
(	0
1	0
defect	0
)	0
.	0
C0NCLUSI0NS	0
:	0
Reassuringly	0
","	0
penicillins	1
","	0
erythromycins	1
","	0
and	0
cephalosporins	1
","	0
although	0
used	0
commonly	0
by	0
pregnant	0
women	0
","	0
were	0
not	0
associated	0
with	0
many	0
birth	3
defects	4
.	0
Sulfonamides	1
and	0
nitrofurantoins	1
were	0
associated	0
with	0
several	0
birth	3
defects	4
","	0
indicating	0
a	0
need	0
for	0
additional	0
scrutiny	0
.	0
Differential	0
impact	0
of	0
immune	0
escape	0
mutations	0
G145R	0
and	0
P120T	0
on	0
the	0
replication	0
of	0
lamivudine	1
-	0
resistant	0
hepatitis	1
B	2
virus	2
e	2
antigen	2
-	0
positive	0
and	0
-	0
negative	0
strains	0
.	0
Immune	0
escape	0
variants	0
of	0
the	0
hepatitis	3
B	4
virus	0
(	0
HBV	0
)	0
represent	0
an	0
emerging	0
clinical	0
challenge	0
","	0
because	0
they	0
can	0
be	0
associated	0
with	0
vaccine	0
escape	0
","	0
HBV	0
reactivation	0
","	0
and	0
failure	0
of	0
diagnostic	0
tests	0
.	0
Recent	0
data	0
suggest	0
a	0
preferential	0
selection	0
of	0
immune	0
escape	0
mutants	0
in	0
distinct	0
peripheral	0
blood	0
leukocyte	0
compartments	0
of	0
infected	0
individuals	0
.	0
We	0
therefore	0
systematically	0
analyzed	0
the	0
functional	0
impact	0
of	0
the	0
most	0
prevalent	0
immune	0
escape	0
variants	0
","	0
the	0
sG145R	0
and	0
sP120T	0
mutants	0
","	0
on	0
the	0
viral	0
replication	0
efficacy	0
and	0
antiviral	0
drug	0
susceptibility	0
of	0
common	0
treatment	0
-	0
associated	0
mutants	0
with	0
resistance	0
to	0
lamivudine	1
(	0
LAM	1
)	0
and	0
/	0
or	0
HBeAg	1
negativity	0
.	0
Replication	0
-	0
competent	0
HBV	0
strains	0
with	0
sG145R	0
or	0
sP120T	0
and	0
LAM	1
resistance	0
(	0
rtM204I	0
or	0
rtL180M	0
/	0
rtM204V	0
)	0
were	0
generated	0
on	0
an	0
HBeAg	1
-	0
positive	0
and	0
an	0
HBeAg	1
-	0
negative	0
background	0
with	0
precore	0
(	0
PC	0
)	0
and	0
basal	0
core	0
promoter	0
(	0
BCP	0
)	0
mutants	0
.	0
The	0
sG145R	0
mutation	0
strongly	0
reduced	0
HBsAg	1
levels	0
and	0
was	0
able	0
to	0
fully	0
restore	0
the	0
impaired	0
replication	0
of	0
LAM	1
-	0
resistant	0
HBV	0
mutants	0
to	0
the	0
levels	0
of	0
wild	0
-	0
type	0
HBV	0
","	0
and	0
PC	0
or	0
BCP	0
mutations	0
further	0
enhanced	0
viral	0
replication	0
.	0
Although	0
the	0
sP120T	0
substitution	0
also	0
impaired	0
HBsAg	1
secretion	0
","	0
it	0
did	0
not	0
enhance	0
the	0
replication	0
of	0
LAM	1
-	0
resistant	0
clones	0
.	0
However	0
","	0
the	0
concomitant	0
occurrence	0
of	0
HBeAg	1
negativity	0
(	0
PC	0
/	0
BCP	0
)	0
","	0
sP120T	0
","	0
and	0
LAM	1
resistance	0
resulted	0
in	0
the	0
restoration	0
of	0
replication	0
to	0
levels	0
of	0
wild	0
-	0
type	0
HBV	0
.	0
In	0
all	0
clones	0
with	0
combined	0
immune	0
escape	0
and	0
LAM	1
resistance	0
mutations	0
","	0
the	0
nucleotide	1
analogues	0
adefovir	1
and	0
tenofovir	1
remained	0
effective	0
in	0
suppressing	0
viral	0
replication	0
in	0
vitro	0
.	0
These	0
findings	0
reveal	0
the	0
differential	0
impact	0
of	0
immune	0
escape	0
variants	0
on	0
the	0
replication	0
and	0
drug	0
susceptibility	0
of	0
complex	0
HBV	0
mutants	0
","	0
supporting	0
the	0
need	0
of	0
close	0
surveillance	0
and	0
treatment	0
adjustment	0
in	0
response	0
to	0
the	0
selection	0
of	0
distinct	0
mutational	0
patterns	0
.	0
Hemolytic	3
anemia	4
associated	0
with	0
the	0
use	0
of	0
omeprazole	1
.	0
0meprazole	1
is	0
the	0
first	0
drug	0
designed	0
to	0
block	0
the	0
final	0
step	0
in	0
the	0
acid	0
secretory	0
process	0
within	0
the	0
parietal	0
cell	0
.	0
It	0
has	0
been	0
shown	0
to	0
be	0
extremely	0
effective	0
in	0
the	0
treatment	0
of	0
peptic	3
ulcer	4
disease	4
","	0
reflux	3
esophagitis	4
","	0
and	0
the	0
Zollinger	3
-	4
Ellison	4
syndrome	4
.	0
Although	0
clinical	0
experience	0
with	0
omeprazole	1
is	0
still	0
limited	0
","	0
many	0
controlled	0
studies	0
have	0
established	0
the	0
short	0
-	0
term	0
safety	0
of	0
this	0
drug	0
.	0
We	0
report	0
the	0
first	0
case	0
of	0
a	0
serious	0
short	0
-	0
term	0
adverse	0
reaction	0
with	0
the	0
use	0
of	0
omeprazole	1
:	0
hemolytic	3
anemia	4
.	0
The	0
patient	0
developed	0
weakness	0
","	0
lethargy	3
","	0
and	0
shortness	3
of	4
breath	4
2	0
days	0
after	0
starting	0
therapy	0
with	0
omeprazole	1
.	0
Two	0
weeks	0
after	0
the	0
initiation	0
of	0
therapy	0
","	0
her	0
hematocrit	0
had	0
decreased	0
from	0
44	0
.	0
1	0
%	0
to	0
20	0
.	0
4	0
%	0
","	0
and	0
she	0
had	0
a	0
positive	0
direct	0
Coombs	0
antiglobulin	0
test	0
and	0
an	0
elevated	0
indirect	0
bilirubin	1
.	0
After	0
she	0
discontinued	0
the	0
omeprazole	1
","	0
her	0
hemoglobin	0
and	0
hematocrit	0
gradually	0
returned	0
to	0
normal	0
.	0
The	0
mechanism	0
by	0
which	0
omeprazole	1
caused	0
the	0
patient	0
'	0
s	0
hemolytic	3
anemia	4
is	0
uncertain	0
","	0
but	0
physicians	0
should	0
be	0
alerted	0
to	0
this	0
possible	0
adverse	0
effect	0
.	0
Phenylephrine	1
but	0
not	0
ephedrine	1
reduces	3
frontal	4
lobe	4
oxygenation	4
following	0
anesthesia	0
-	0
induced	0
hypotension	3
.	0
BACKGR0UND	0
:	0
Vasopressor	0
agents	0
are	0
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to	0
correct	0
anesthesia	0
-	0
induced	0
hypotension	3
.	0
We	0
describe	0
the	0
effect	0
of	0
phenylephrine	1
and	0
ephedrine	1
on	0
frontal	0
lobe	0
oxygenation	0
(	0
S	0
(	0
c	0
)	0
0	0
(	0
2	0
)	0
)	0
following	0
anesthesia	0
-	0
induced	0
hypotension	3
.	0
METH0DS	0
:	0
Following	0
induction	0
of	0
anesthesia	0
by	0
fentanyl	1
(	0
0	0
.	0
15	0
mg	0
kg	0
(	0
-	0
1	0
)	0
)	0
and	0
propofol	1
(	0
2	0
.	0
0	0
mg	0
kg	0
(	0
-	0
1	0
)	0
)	0
","	0
13	0
patients	0
received	0
phenylephrine	1
(	0
0	0
.	0
1	0
mg	0
iv	0
)	0
and	0
12	0
patients	0
received	0
ephedrine	1
(	0
10	0
mg	0
iv	0
)	0
to	0
restore	0
mean	0
arterial	0
pressure	0
(	0
MAP	0
)	0
.	0
Heart	0
rate	0
(	0
HR	0
)	0
","	0
MAP	0
","	0
stroke	3
volume	0
(	0
SV	0
)	0
","	0
cardiac	0
output	0
(	0
C0	0
)	0
","	0
and	0
frontal	0
lobe	0
oxygenation	0
(	0
S	0
(	0
c	0
)	0
0	0
(	0
2	0
)	0
)	0
were	0
registered	0
.	0
RESULTS	0
:	0
Induction	0
of	0
anesthesia	0
was	0
followed	0
by	0
a	3
decrease	4
in	4
MAP	4
","	4
HR	4
","	4
SV	4
","	4
and	4
C0	4
concomitant	0
with	0
an	0
elevation	0
in	0
S	0
(	0
c	0
)	0
0	0
(	0
2	0
)	0
.	0
After	0
administration	0
of	0
phenylephrine	1
","	0
MAP	0
increased	0
(	0
51	0
+	0
/	0
-	0
12	0
to	0
81	0
+	0
/	0
-	0
13	0
mmHg	0
;	0
P	0
<	0
0	0
.	0
1	0
;	0
mean	0
+	0
/	0
-	0
SD	0
)	0
.	0
However	0
","	0
a	0
14	0
%	0
(	0
from	0
70	0
+	0
/	0
-	0
8	0
%	0
to	0
60	0
+	0
/	0
-	0
7	0
%	0
)	0
reduction	0
in	0
S	0
(	0
c	0
)	0
0	0
(	0
2	0
)	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
followed	0
with	0
no	0
change	0
in	0
C0	0
(	0
3	0
.	0
7	0
+	0
/	0
-	0
1	0
.	0
1	0
to	0
3	0
.	0
4	0
+	0
/	0
-	0
0	0
.	0
9	0
l	0
min	0
(	0
-	0
1	0
)	0
)	0
.	0
The	0
administration	0
of	0
ephedrine	1
led	0
to	0
a	0
similar	0
increase	0
in	0
MAP	0
(	0
53	0
+	0
/	0
-	0
9	0
to	0
79	0
+	0
/	0
-	0
8	0
mmHg	0
;	0
P	0
<	0
0	0
.	0
1	0
)	0
","	0
restored	0
C0	0
(	0
3	0
.	0
2	0
+	0
/	0
-	0
1	0
.	0
2	0
to	0
5	0
.	0
0	0
+	0
/	0
-	0
1	0
.	0
3	0
l	0
min	0
(	0
-	0
1	0
)	0
)	0
","	0
and	0
preserved	0
S	0
(	0
c	0
)	0
0	0
(	0
2	0
)	0
.	0
C0NCLUSI0NS	0
:	0
The	0
utilization	0
of	0
phenylephrine	1
to	0
correct	0
hypotension	3
induced	0
by	0
anesthesia	0
has	0
a	0
negative	0
impact	0
on	0
S	0
(	0
c	0
)	0
0	0
(	0
2	0
)	0
while	0
ephedrine	1
maintains	0
frontal	0
lobe	0
oxygenation	0
potentially	0
related	0
to	0
an	0
increase	0
in	0
C0	0
.	0
Prolonged	0
elevation	0
of	0
plasma	0
argatroban	1
in	0
a	0
cardiac	0
transplant	0
patient	0
with	0
a	0
suspected	0
history	0
of	0
heparin	1
-	0
induced	0
thrombocytopenia	3
with	0
thrombosis	3
.	0
BACKGR0UND	0
:	0
Direct	0
thrombin	0
inhibitors	0
(	0
DTIs	0
)	0
provide	0
an	0
alternative	0
method	0
of	0
anticoagulation	0
for	0
patients	0
with	0
a	0
history	0
of	0
heparin	1
-	0
induced	0
thrombocytopenia	3
(	0
HIT	3
)	0
or	0
HIT	3
with	0
thrombosis	3
(	0
HITT	3
)	0
undergoing	0
cardiopulmonary	0
bypass	0
(	0
CPB	0
)	0
.	0
In	0
the	0
following	0
report	0
","	0
a	0
65	0
-	0
year	0
-	0
old	0
critically	3
ill	4
patient	0
with	0
a	0
suspected	0
history	0
of	0
HITT	3
was	0
administered	0
argatroban	1
for	0
anticoagulation	0
on	0
bypass	0
during	0
heart	0
transplantation	0
.	0
The	0
patient	0
required	0
massive	0
transfusion	0
support	0
(	0
55	0
units	0
of	0
red	0
blood	0
cells	0
","	0
42	0
units	0
of	0
fresh	0
-	0
frozen	0
plasma	0
","	0
40	0
units	0
of	0
cryoprecipitate	0
","	0
40	0
units	0
of	0
platelets	0
","	0
and	0
three	0
doses	0
of	0
recombinant	0
Factor	0
VIIa	0
)	0
for	0
severe	0
intraoperative	3
and	4
postoperative	4
bleeding	4
.	0
STUDY	0
DESIGN	0
AND	0
METH0DS	0
:	0
Plasma	0
samples	0
from	0
before	0
and	0
after	0
CPB	0
were	0
analyzed	0
postoperatively	0
for	0
argatroban	1
concentration	0
using	0
a	0
modified	0
ecarin	0
clotting	0
time	0
(	0
ECT	0
)	0
assay	0
.	0
RESULTS	0
:	0
Unexpectedly	0
high	0
concentrations	0
of	0
argatroban	1
were	0
measured	0
in	0
these	0
samples	0
(	0
range	0
","	0
0	0
-	0
32	0
microg	0
/	0
mL	0
)	0
","	0
and	0
a	0
prolonged	0
plasma	0
argatroban	1
half	0
life	0
(	0
t	0
(	0
1	0
/	0
2	0
)	0
)	0
of	0
514	0
minutes	0
was	0
observed	0
(	0
published	0
elimination	0
t	0
(	0
1	0
/	0
2	0
)	0
is	0
39	0
-	0
51	0
minutes	0
[	0
<	0
or	0
=	0
181	0
minutes	0
with	0
hepatic	3
impairment	4
]	0
)	0
.	0
C0NCLUSI0NS	0
:	0
Correlation	0
of	0
plasma	0
argatroban	1
concentration	0
versus	0
the	0
patient	0
'	0
s	0
coagulation	0
variables	0
and	0
clinical	0
course	0
suggest	0
that	0
prolonged	0
elevated	0
levels	0
of	0
plasma	0
argatroban	1
may	0
have	0
contributed	0
to	0
the	0
patient	0
'	0
s	0
extended	0
coagulopathy	3
.	0
Because	0
DTIs	0
do	0
not	0
have	0
reversal	0
agents	0
","	0
surgical	0
teams	0
and	0
transfusion	0
services	0
should	0
remain	0
aware	0
of	0
the	0
possibility	0
of	0
massive	0
transfusion	0
events	0
during	0
anticoagulation	0
with	0
these	0
agents	0
.	0
This	0
is	0
the	0
first	0
report	0
to	0
measure	0
plasma	0
argatroban	1
concentration	0
in	0
the	0
context	0
of	0
CPB	0
and	0
extended	0
coagulopathy	3
.	0
The	0
effects	0
of	0
the	0
adjunctive	0
bupropion	1
on	0
male	0
sexual	3
dysfunction	4
induced	0
by	0
a	0
selective	1
serotonin	2
reuptake	2
inhibitor	2
:	0
a	0
double	0
-	0
blind	0
placebo	0
-	0
controlled	0
and	0
randomized	0
study	0
.	0
0BJECTIVE	0
:	0
To	0
determine	0
the	0
safety	0
and	0
efficacy	0
of	0
adjunctive	0
bupropion	1
sustained	0
-	0
release	0
(	0
SR	0
)	0
on	0
male	0
sexual	3
dysfunction	4
(	0
SD	3
)	0
induced	0
by	0
a	0
selective	1
serotonin	2
reuptake	2
inhibitor	2
(	0
SSRI	1
)	0
","	0
as	0
SD	3
is	0
a	0
common	0
side	0
-	0
effect	0
of	0
SSRIs	1
and	0
the	0
most	0
effective	0
treatments	0
have	0
yet	0
to	0
be	0
determined	0
.	0
PATIENTS	0
AND	0
METH0DS	0
:	0
The	0
randomized	0
sample	0
consisted	0
of	0
234	0
euthymic	0
men	0
who	0
were	0
receiving	0
some	0
type	0
of	0
SSRI	1
.	0
The	0
men	0
were	0
randomly	0
assigned	0
to	0
bupropion	1
SR	0
(	0
150	0
mg	0
twice	0
daily	0
","	0
117	0
)	0
or	0
placebo	0
(	0
twice	0
daily	0
","	0
117	0
)	0
for	0
12	0
weeks	0
.	0
Efficacy	0
was	0
evaluated	0
using	0
the	0
Clinical	0
Global	0
Impression	0
-	0
Sexual	0
Function	0
(	0
CGI	0
-	0
SF	0
;	0
the	0
primary	0
outcome	0
measure	0
)	0
","	0
the	0
International	0
Index	0
of	0
Erectile	0
Function	0
(	0
IIEF	0
)	0
","	0
Arizona	0
Sexual	0
Experience	0
Scale	0
(	0
ASEX	0
)	0
","	0
and	0
Erectile	3
Dysfunction	4
Inventory	0
of	0
Treatment	0
Satisfaction	0
(	0
EDITS	0
)	0
(	0
secondary	0
outcome	0
measures	0
)	0
.	0
Participants	0
were	0
followed	0
biweekly	0
during	0
study	0
period	0
.	0
RESULTS	0
:	0
After	0
12	0
weeks	0
of	0
treatment	0
","	0
the	0
mean	0
(	0
sd	0
)	0
scores	0
for	0
CGI	0
-	0
SF	0
were	0
significantly	0
lower	0
","	0
i	0
.	0
e	0
.	0
better	0
","	0
in	0
patients	0
on	0
bupropion	1
SR	0
","	0
at	0
2	0
.	0
4	0
(	0
1	0
.	0
2	0
)	0
","	0
than	0
in	0
the	0
placebo	0
group	0
","	0
at	0
3	0
.	0
9	0
(	0
1	0
.	0
1	0
)	0
(	0
P	0
=	0
0	0
.	0
1	0
)	0
.	0
Men	0
who	0
received	0
bupropion	1
had	0
a	0
significant	0
increase	0
in	0
the	0
total	0
IIEF	0
score	0
(	0
54	0
.	0
4	0
%	0
vs	0
1	0
.	0
2	0
%	0
;	0
P	0
=	0
0	0
.	0
3	0
)	0
","	0
and	0
in	0
the	0
five	0
different	0
domains	0
of	0
the	0
IIEF	0
.	0
Total	0
ASEX	0
scores	0
were	0
significantly	0
lower	0
","	0
i	0
.	0
e	0
.	0
better	0
","	0
among	0
men	0
who	0
received	0
bupropion	1
than	0
placebo	0
","	0
at	0
15	0
.	0
5	0
(	0
4	0
.	0
3	0
)	0
vs	0
21	0
.	0
5	0
(	0
4	0
.	0
7	0
)	0
(	0
P	0
=	0
0	0
.	0
2	0
)	0
.	0
The	0
EDITS	0
scores	0
were	0
67	0
.	0
4	0
(	0
10	0
.	0
2	0
)	0
for	0
the	0
bupropion	1
and	0
36	0
.	0
3	0
(	0
11	0
.	0
7	0
)	0
for	0
the	0
placebo	0
group	0
(	0
P	0
=	0
0	0
.	0
1	0
)	0
.	0
The	0
ASEX	0
score	0
and	0
CGI	0
-	0
SF	0
score	0
were	0
correlated	0
(	0
P	0
=	0
0	0
.	0
3	0
)	0
.	0
In	0
linear	0
regression	0
analyses	0
the	0
CGI	0
-	0
SF	0
score	0
was	0
not	0
affected	0
significantly	0
by	0
the	0
duration	0
of	0
SD	3
","	0
type	0
of	0
SSRI	1
used	0
and	0
age	0
.	0
C0NCLUSI0NS	0
:	0
Bupropion	1
is	0
an	0
effective	0
treatment	0
for	0
male	0
SD	3
induced	0
by	0
SSRIs	1
.	0
These	0
results	0
provide	0
empirical	0
support	0
for	0
conducting	0
a	0
further	0
study	0
of	0
bupropion	1
.	0
Prevention	0
of	0
seizures	3
and	0
reorganization	0
of	0
hippocampal	0
functions	0
by	0
transplantation	0
of	0
bone	0
marrow	0
cells	0
in	0
the	0
acute	0
phase	0
of	0
experimental	0
epilepsy	3
.	0
In	0
this	0
study	0
","	0
we	0
investigated	0
the	0
therapeutic	0
potential	0
of	0
bone	0
marrow	0
mononuclear	0
cells	0
(	0
BMCs	0
)	0
in	0
a	0
model	0
of	0
epilepsy	3
induced	0
by	0
pilocarpine	1
in	0
rats	0
.	0
BMCs	0
obtained	0
from	0
green	0
fluorescent	0
protein	0
(	0
GFP	0
)	0
transgenic	0
mice	0
or	0
rats	0
were	0
transplanted	0
intravenously	0
after	0
induction	0
of	0
status	3
epilepticus	4
(	0
SE	3
)	0
.	0
Spontaneous	3
recurrent	4
seizures	4
(	0
SRS	3
)	0
were	0
monitored	0
using	0
Racine	0
'	0
s	0
seizure	3
severity	0
scale	0
.	0
All	0
of	0
the	0
rats	0
in	0
the	0
saline	0
-	0
treated	0
epileptic	3
control	0
group	0
developed	0
SRS	3
","	0
whereas	0
none	0
of	0
the	0
BMC	0
-	0
treated	0
epileptic	3
animals	0
had	0
seizures	3
in	0
the	0
short	0
term	0
(	0
15	0
days	0
after	0
transplantation	0
)	0
","	0
regardless	0
of	0
the	0
BMC	0
source	0
.	0
0ver	0
the	0
long	0
-	0
term	0
chronic	0
phase	0
(	0
120	0
days	0
after	0
transplantation	0
)	0
","	0
only	0
25	0
%	0
of	0
BMC	0
-	0
treated	0
epileptic	3
animals	0
had	0
seizures	3
","	0
but	0
with	0
a	0
lower	0
frequency	0
and	0
duration	0
compared	0
to	0
the	0
epileptic	3
control	0
group	0
.	0
The	0
density	0
of	0
hippocampal	0
neurons	0
in	0
the	0
brains	0
of	0
animals	0
treated	0
with	0
BMCs	0
was	0
markedly	0
preserved	0
.	0
At	0
hippocampal	0
Schaeffer	0
collateral	0
-	0
CA1	0
synapses	0
","	0
long	0
-	0
term	0
potentiation	0
was	0
preserved	0
in	0
BMC	0
-	0
transplanted	0
rats	0
compared	0
to	0
epileptic	3
controls	0
.	0
The	0
donor	0
-	0
derived	0
GFP	0
(	0
+	0
)	0
cells	0
were	0
rarely	0
found	0
in	0
the	0
brains	0
of	0
transplanted	0
epileptic	3
rats	0
.	0
In	0
conclusion	0
","	0
treatment	0
with	0
BMCs	0
can	0
prevent	0
the	0
development	0
of	0
chronic	0
seizures	3
","	0
reduce	0
neuronal	3
loss	4
","	0
and	0
influence	0
the	0
reorganization	0
of	0
the	0
hippocampal	0
neuronal	0
network	0
.	0
Normalizing	0
effects	0
of	0
modafinil	1
on	0
sleep	0
in	0
chronic	0
cocaine	1
users	0
.	0
0BJECTIVE	0
:	0
The	0
purpose	0
of	0
the	0
present	0
study	0
was	0
to	0
determine	0
the	0
effect	0
of	0
morning	0
-	0
dosed	0
modafinil	1
on	0
sleep	0
and	0
daytime	3
sleepiness	4
in	0
chronic	0
cocaine	1
users	0
.	0
METH0D	0
:	0
Twenty	0
cocaine	1
-	0
dependent	0
participants	0
were	0
randomly	0
assigned	0
to	0
receive	0
modafinil	1
","	0
400	0
mg	0
(	0
N	0
=	0
10	0
)	0
","	0
or	0
placebo	0
(	0
N	0
=	0
10	0
)	0
every	0
morning	0
at	0
7	0
:	0
30	0
a	0
.	0
m	0
.	0
for	0
16	0
days	0
in	0
an	0
inpatient	0
","	0
double	0
-	0
blind	0
randomized	0
trial	0
.	0
Participants	0
underwent	0
polysomnographic	0
sleep	0
recordings	0
on	0
days	0
1	0
to	0
3	0
","	0
7	0
to	0
9	0
","	0
and	0
14	0
to	0
16	0
(	0
first	0
","	0
second	0
","	0
and	0
third	0
weeks	0
of	0
abstinence	0
)	0
.	0
The	0
Multiple	0
Sleep	0
Latency	0
Test	0
was	0
performed	0
at	0
11	0
:	0
30	0
a	0
.	0
m	0
.	0
","	0
2	0
:	0
0	0
p	0
.	0
m	0
.	0
","	0
and	0
4	0
:	0
30	0
p	0
.	0
m	0
.	0
on	0
days	0
2	0
","	0
8	0
","	0
and	0
15	0
.	0
For	0
comparison	0
of	0
sleep	0
architecture	0
variables	0
","	0
12	0
healthy	0
comparison	0
participants	0
underwent	0
a	0
single	0
night	0
of	0
experimental	0
polysomnography	0
that	0
followed	0
1	0
night	0
of	0
accommodation	0
polysomnography	0
.	0
RESULTS	0
:	0
Progressive	0
abstinence	0
from	0
cocaine	1
was	0
associated	0
with	0
worsening	0
of	0
all	0
measured	0
polysomnographic	0
sleep	0
outcomes	0
.	0
Compared	0
with	0
placebo	0
","	0
modafinil	1
decreased	0
nighttime	0
sleep	0
latency	0
and	0
increased	0
slow	0
-	0
wave	0
sleep	0
time	0
in	0
cocaine	1
-	0
dependent	0
participants	0
.	0
The	0
effect	0
of	0
modafinil	1
interacted	0
with	0
the	0
abstinence	0
week	0
and	0
was	0
associated	0
with	0
longer	0
total	0
sleep	0
time	0
and	0
shorter	0
REM	0
sleep	0
latency	0
in	0
the	0
third	0
week	0
of	0
abstinence	0
.	0
Comparison	0
of	0
slow	0
-	0
wave	0
sleep	0
time	0
","	0
total	0
sleep	0
time	0
","	0
and	0
sleep	0
latency	0
in	0
cocaine	1
-	0
dependent	0
and	0
healthy	0
participants	0
revealed	0
a	0
normalizing	0
effect	0
of	0
modafinil	1
in	0
cocaine	1
-	0
dependent	0
participants	0
.	0
Modafinil	1
was	0
associated	0
with	0
increased	0
daytime	0
sleep	0
latency	0
","	0
as	0
measured	0
by	0
the	0
Multiple	0
Sleep	0
Latency	0
Test	0
","	0
and	0
a	0
nearly	0
significant	0
decrease	0
in	0
subjective	0
daytime	3
sleepiness	4
.	0
C0NCLUSI0NS	0
:	0
Morning	0
-	0
dosed	0
modafinil	1
promotes	0
nocturnal	0
sleep	0
","	0
normalizes	0
sleep	0
architecture	0
","	0
and	0
decreases	0
daytime	3
sleepiness	4
in	0
abstinent	0
cocaine	1
users	0
.	0
These	0
effects	0
may	0
be	0
relevant	0
in	0
the	0
treatment	0
of	0
cocaine	1
dependence	0
.	0
Safety	0
of	0
transesophageal	0
echocardiography	0
in	0
adults	0
:	0
study	0
in	0
a	0
multidisciplinary	0
hospital	0
.	0
BACKGR0UND	0
:	0
TEE	0
is	0
a	0
semi	0
-	0
invasive	0
tool	0
broadly	0
used	0
and	0
its	0
utilization	0
associated	0
to	0
sedatives	0
drugs	0
might	0
to	0
affect	0
the	0
procedure	0
safety	0
.	0
0BJECTIVE	0
:	0
to	0
analyze	0
aspects	0
of	0
TEE	0
safety	0
associated	0
to	0
the	0
use	0
of	0
Midazolan	1
(	0
MZ	1
)	0
and	0
Flumazenil	1
(	0
FL	1
)	0
and	0
the	0
influence	0
of	0
the	0
clinical	0
variables	0
on	0
the	0
event	0
rate	0
.	0
METH0D	0
:	0
prospective	0
study	0
with	0
137	0
patients	0
that	0
underwent	0
TEE	0
with	0
MZ	1
associated	0
to	0
moderate	0
sedation	0
.	0
We	0
analyzed	0
the	0
following	0
events	0
:	0
complications	0
related	0
with	0
the	0
topical	0
anesthesia	0
","	0
with	0
MZ	1
use	0
and	0
with	0
the	0
procedure	0
.	0
Uni	0
-	0
and	0
multivariate	0
analyses	0
were	0
used	0
to	0
test	0
the	0
influence	0
of	0
the	0
clinical	0
variables	0
:	0
age	0
","	0
sex	0
","	0
stroke	3
","	0
myocardiopathy	3
(	0
MP	3
)	0
","	0
duration	0
of	0
the	0
test	0
","	0
mitral	3
regurgitation	4
(	0
MR	3
)	0
and	0
the	0
MZ	1
dose	0
.	0
RESULTS	0
:	0
All	0
patients	0
(	0
65	0
+	0
/	0
-	0
16	0
yrs	0
;	0
58	0
%	0
males	0
)	0
finished	0
the	0
examination	0
.	0
The	0
mean	0
doses	0
of	0
MZ	1
and	0
FL	1
were	0
4	0
.	0
3	0
+	0
/	0
-	0
1	0
.	0
9	0
mg	0
and	0
0	0
.	0
28	0
+	0
/	0
-	0
0	0
.	0
2	0
mg	0
","	0
respectively	0
.	0
The	0
duration	0
of	0
the	0
examination	0
and	0
the	0
mean	0
ejection	0
fraction	0
(	0
EF	0
)	0
were	0
16	0
.	0
4	0
+	0
/	0
-	0
6	0
.	0
1	0
minutes	0
and	0
60	0
+	0
/	0
-	0
9	0
%	0
","	0
respectively	0
.	0
Mild	0
hypoxia	3
(	0
S02	0
<	0
90	0
%	0
)	0
was	0
the	0
most	0
common	0
event	0
(	0
11	0
patients	0
)	0
;	0
3	0
patients	0
(	0
2	0
%	0
)	0
presented	0
transient	0
hypoxia	3
due	0
to	0
upper	0
airway	3
obstruction	4
by	0
probe	0
introduction	0
and	0
8	0
(	0
5	0
.	0
8	0
%	0
)	0
due	0
to	0
hypoxia	3
caused	0
by	0
MZ	1
use	0
.	0
Transient	0
hypotension	3
(	0
SAP	0
<	0
90mmHg	0
)	0
occurred	0
in	0
1	0
patient	0
(	0
0	0
.	0
7	0
%	0
)	0
.	0
The	0
multivariate	0
analysis	0
showed	0
that	0
severe	0
MR	3
","	0
MP	3
(	0
EF	0
<	0
45	0
%	0
)	0
and	0
high	0
doses	0
of	0
MZ	1
(	0
>	0
5mg	0
)	0
were	0
associated	0
with	0
events	0
(	0
p	0
<	0
0	0
.	0
1	0
)	0
.	0
The	0
EF	0
was	0
40	0
%	0
","	0
in	0
the	0
group	0
with	0
MP	3
and	0
44	0
%	0
in	0
the	0
group	0
with	0
severe	0
MR	3
and	0
it	0
can	0
be	0
a	0
factor	0
associated	0
with	0
clinical	0
events	0
in	0
the	0
last	0
group	0
.	0
C0NCLUSI0N	0
:	0
TEE	0
with	0
sedation	0
presents	0
a	0
low	0
rate	0
of	0
events	0
.	0
There	0
were	0
no	0
severe	0
events	0
and	0
there	0
was	0
no	0
need	0
to	0
interrupt	0
the	0
examinations	0
.	0
Effect	0
of	0
direct	0
intracoronary	0
administration	0
of	0
methylergonovine	1
in	0
patients	0
with	0
and	0
without	0
variant	3
angina	4
.	0
The	0
effects	0
of	0
intracoronary	0
administration	0
of	0
methylergonovine	1
were	0
studied	0
in	0
21	0
patients	0
with	0
variant	3
angina	4
and	0
22	0
patients	0
with	0
atypical	0
chest	3
pain	4
and	0
in	0
others	0
without	0
angina	3
pectoris	4
(	0
control	0
group	0
)	0
.	0
Methylergonovine	1
was	0
administered	0
continuously	0
at	0
a	0
rate	0
of	0
10	0
micrograms	0
/	0
min	0
up	0
to	0
50	0
micrograms	0
.	0
In	0
all	0
patients	0
with	0
variant	3
angina	4
","	0
coronary	3
spasm	4
was	0
provoked	0
at	0
a	0
mean	0
dose	0
of	0
28	0
+	0
/	0
-	0
13	0
micrograms	0
(	0
mean	0
+	0
/	0
-	0
SD	0
)	0
.	0
In	0
the	0
control	0
group	0
neither	0
ischemic	0
ST	0
change	0
nor	0
localized	0
spasm	3
occurred	0
.	0
The	0
basal	0
tone	0
of	0
the	0
right	0
coronary	0
artery	0
was	0
significantly	0
lower	0
than	0
that	0
of	0
the	0
left	0
coronary	0
artery	0
.	0
The	0
percentage	0
of	0
vasoconstriction	0
of	0
the	0
right	0
coronary	0
artery	0
was	0
significantly	0
higher	0
than	0
that	0
of	0
the	0
left	0
coronary	0
artery	0
.	0
These	0
results	0
suggest	0
that	0
spasm	3
provocation	0
tests	0
","	0
which	0
use	0
an	0
intracoronary	0
injection	0
of	0
a	0
relatively	0
low	0
dose	0
of	0
methylergonovine	1
","	0
have	0
a	0
high	0
sensitivity	0
in	0
variant	3
angina	4
and	0
the	0
vasoreactivity	0
of	0
the	0
right	0
coronary	0
artery	0
may	0
be	0
greater	0
than	0
that	0
of	0
the	0
other	0
coronary	0
arteries	0
.	0
0ral	0
manifestations	0
of	0
"	0
meth	3
mouth	4
"	0
:	0
a	0
case	0
report	0
.	0
AIM	0
:	0
The	0
aim	0
of	0
the	0
documentation	0
of	0
this	0
clinical	0
case	0
is	0
to	0
make	0
clinicians	0
aware	0
of	0
"	0
meth	3
mouth	4
"	0
and	0
the	0
medical	0
risks	0
associated	0
with	0
this	0
serious	0
condition	0
.	0
BACKGR0UND	0
:	0
Methamphetamine	1
is	0
a	0
very	0
addictive	0
","	0
powerful	0
stimulant	0
that	0
increases	0
wakefulness	0
and	0
physical	0
activity	0
and	0
can	0
produce	0
other	0
effects	0
such	0
as	0
cardiac	3
dysrhythmias	4
","	0
hypertension	3
","	0
hallucinations	3
","	0
and	0
violent	3
behavior	4
.	0
Dental	0
patients	0
abusing	0
methamphetamine	1
can	0
present	0
with	0
poor	0
oral	0
hygiene	0
","	0
xerostomia	3
","	0
rampant	0
caries	3
(	0
"	0
meth	3
mouth	4
"	0
)	0
","	0
and	0
excessive	0
tooth	3
wear	4
.	0
0ral	0
rehabilitation	0
of	0
patients	0
using	0
methamphetamine	1
can	0
be	0
challenging	0
.	0
CASE	0
DESCRIPTI0N	0
:	0
A	0
30	0
-	0
year	0
-	0
old	0
Caucasian	0
woman	0
presented	0
with	0
dental	0
pain	3
","	0
bad	3
breath	4
","	0
and	0
self	0
-	0
reported	0
poor	0
esthetics	0
.	0
A	0
comprehensive	0
examination	0
including	0
her	0
medical	0
history	0
","	0
panoramic	0
radiograph	0
","	0
and	0
intraoral	0
examination	0
revealed	0
19	0
carious	3
lesions	4
","	0
which	0
is	0
not	0
very	0
common	0
for	0
a	0
healthy	0
adult	0
.	0
She	0
reported	0
her	0
use	0
of	0
methamphetamine	1
for	0
five	0
years	0
and	0
had	0
not	0
experienced	0
any	0
major	0
carious	3
episodes	4
before	0
she	0
started	0
using	0
the	0
drug	0
.	0
SUMMARY	0
:	0
The	0
patient	0
'	0
s	0
medical	0
and	0
dental	0
histories	0
along	0
with	0
radiographic	0
and	0
clinical	0
findings	0
lead	0
to	0
a	0
diagnosis	0
of	0
"	0
meth	3
mouth	4
.	0
"	0
Although	0
three	0
different	0
dental	0
treatment	0
modalities	0
(	0
either	0
conventional	0
or	0
implant	0
-	0
supported	0
)	0
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to	0
the	0
patient	0
since	0
August	0
2007	0
","	0
the	0
patient	0
has	0
yet	0
to	0
initiate	0
any	0
treatment	0
.	0
CLINICAL	0
SIGNIFICANCE	0
:	0
This	0
clinical	0
case	0
showing	0
oral	0
manifestations	0
of	0
meth	3
mouth	4
was	0
presented	0
to	0
help	0
dental	0
practitioners	0
recognize	0
and	0
manage	0
patients	0
who	0
may	0
be	0
abusing	0
methamphetamines	1
.	0
Dental	0
practitioners	0
also	0
may	0
be	0
skeptical	0
about	0
the	0
reliability	0
of	0
appointment	0
keeping	0
by	0
these	0
patients	0
","	0
as	0
they	0
frequently	0
miss	0
their	0
appointments	0
without	0
reasonable	0
justification	0
.	0
Antituberculosis	1
therapy	0
-	0
induced	0
acute	3
liver	4
failure	4
:	0
magnitude	0
","	0
profile	0
","	0
prognosis	0
","	0
and	0
predictors	0
of	0
outcome	0
.	0
Antituberculosis	1
therapy	0
(	0
ATT	0
)	0
-	0
associated	0
acute	3
liver	4
failure	4
(	0
ATT	0
-	0
ALF	3
)	0
is	0
the	0
commonest	0
drug	0
-	0
induced	0
ALF	3
in	0
South	0
Asia	0
.	0
Prospective	0
studies	0
on	0
ATT	0
-	0
ALF	3
are	0
lacking	0
.	0
The	0
current	0
study	0
prospectively	0
evaluated	0
the	0
magnitude	0
","	0
clinical	0
course	0
","	0
outcome	0
","	0
and	0
prognostic	0
factors	0
in	0
ATT	0
-	0
ALF	3
.	0
From	0
January	0
1986	0
to	0
January	0
2009	0
","	0
1223	0
consecutive	0
ALF	3
patients	0
were	0
evaluated	0
:	0
ATT	0
alone	0
was	0
the	0
cause	0
in	0
70	0
(	0
5	0
.	0
7	0
%	0
)	0
patients	0
.	0
Another	0
15	0
(	0
1	0
.	0
2	0
%	0
)	0
had	0
ATT	0
and	0
simultaneous	0
hepatitis	3
virus	4
infection	4
.	0
In	0
44	0
(	0
62	0
.	0
8	0
%	0
)	0
patients	0
","	0
ATT	0
was	0
prescribed	0
empirically	0
without	0
definitive	0
evidence	0
of	0
tuberculosis	3
.	0
ATT	0
-	0
ALF	3
patients	0
were	0
younger	0
(	0
32	0
.	0
87	0
[	0
+	0
/	0
-	0
15	0
.	0
8	0
]	0
years	0
)	0
","	0
and	0
49	0
(	0
70	0
%	0
)	0
of	0
them	0
were	0
women	0
.	0
Most	0
had	0
hyperacute	0
presentation	0
;	0
the	0
median	0
icterus	3
encephalopathy	3
interval	0
was	0
4	0
.	0
5	0
(	0
0	0
-	0
30	0
)	0
days	0
.	0
The	0
median	0
duration	0
of	0
ATT	0
before	0
ALF	3
was	0
30	0
(	0
7	0
-	0
350	0
)	0
days	0
.	0
At	0
presentation	0
","	0
advanced	0
encephalopathy	3
and	0
cerebral	3
edema	4
were	0
present	0
in	0
51	0
(	0
76	0
%	0
)	0
and	0
29	0
(	0
41	0
.	0
4	0
%	0
)	0
patients	0
","	0
respectively	0
.	0
Gastrointestinal	3
bleed	4
","	0
seizures	3
","	0
infection	3
","	0
and	0
acute	3
renal	4
failure	4
were	0
documented	0
in	0
seven	0
(	0
10	0
%	0
)	0
","	0
five	0
(	0
7	0
.	0
1	0
%	0
)	0
","	0
26	0
(	0
37	0
.	0
1	0
%	0
)	0
","	0
and	0
seven	0
(	0
10	0
%	0
)	0
patients	0
","	0
respectively	0
.	0
Compared	0
with	0
hepatitis	3
E	4
virus	0
(	0
HEV	0
)	0
and	0
non	0
-	0
A	0
non	0
-	0
E	0
-	0
induced	0
ALF	3
","	0
ATT	0
-	0
ALF	3
patients	0
had	0
nearly	0
similar	0
presentations	0
except	0
for	0
older	0
age	0
and	0
less	0
elevation	0
of	0
liver	0
enzymes	0
.	0
The	0
mortality	0
rate	0
among	0
patients	0
with	0
ATT	0
-	0
ALF	3
was	0
high	0
(	0
67	0
.	0
1	0
%	0
","	0
n	0
=	0
47	0
)	0
","	0
and	0
only	0
23	0
(	0
32	0
.	0
9	0
%	0
)	0
patients	0
recovered	0
with	0
medical	0
treatment	0
.	0
In	0
multivariate	0
analysis	0
","	0
three	0
factors	0
independently	0
predicted	0
mortality	0
:	0
serum	0
bilirubin	1
(	0
>	0
or	0
=	0
10	0
.	0
8	0
mg	0
/	0
dL	0
)	0
","	0
prothrombin	0
time	0
(	0
PT	0
)	0
prolongation	0
(	0
>	0
or	0
=	0
26	0
seconds	0
)	0
","	0
and	0
grade	0
III	0
/	0
IV	0
encephalopathy	3
at	0
presentation	0
.	0
C0NCLUSI0N	0
:	0
ATT	0
-	0
ALF	3
constituted	0
5	0
.	0
7	0
%	0
of	0
ALF	3
at	0
our	0
center	0
and	0
had	0
a	0
high	0
mortality	0
rate	0
.	0
Because	0
the	0
mortality	0
rate	0
is	0
so	0
high	0
","	0
determining	0
which	0
factors	0
are	0
predictors	0
is	0
less	0
important	0
.	0
A	0
high	0
proportion	0
of	0
patients	0
had	0
consumed	0
ATT	0
empirically	0
","	0
which	0
could	0
have	0
been	0
prevented	0
.	0
Design	0
and	0
analysis	0
of	0
the	0
HYPREN	0
-	0
trial	0
:	0
safety	0
of	0
enalapril	1
and	0
prazosin	1
in	0
the	0
initial	0
treatment	0
phase	0
of	0
patients	0
with	0
congestive	3
heart	4
failure	4
.	0
Since	0
the	0
introduction	0
of	0
angiotensin	1
converting	2
enzyme	2
(	2
ACE	2
)	2
inhibitors	2
into	0
the	0
adjunctive	0
treatment	0
of	0
patients	0
with	0
congestive	3
heart	4
failure	4
","	0
cases	0
of	0
severe	0
hypotension	3
","	0
especially	0
on	0
the	0
first	0
day	0
of	0
treatment	0
","	0
have	0
occasionally	0
been	0
reported	0
.	0
To	0
assess	0
the	0
safety	0
of	0
the	0
ACE	1
inhibitor	2
enalapril	1
a	0
multicenter	0
","	0
randomized	0
","	0
prazosin	1
-	0
controlled	0
trial	0
was	0
designed	0
that	0
compared	0
the	0
incidence	0
and	0
severity	0
of	0
symptomatic	0
hypotension	3
on	0
the	0
first	0
day	0
of	0
treatment	0
.	0
Trial	0
medication	0
was	0
2	0
.	0
5	0
mg	0
enalapril	1
or	0
0	0
.	0
5	0
prazosin	1
.	0
Subjects	0
were	0
1210	0
inpatients	0
with	0
New	0
York	0
Heart	0
Association	0
(	0
NYHA	0
)	0
functional	0
class	0
II	0
and	0
III	0
.	0
Patients	0
who	0
received	0
enalapril	1
experienced	0
clinically	0
and	0
statistically	0
significantly	0
less	0
symptomatic	0
hypotension	3
(	0
5	0
.	0
2	0
%	0
)	0
than	0
the	0
patients	0
who	0
received	0
prazosin	1
(	0
12	0
.	0
9	0
%	0
)	0
.	0
All	0
patients	0
recovered	0
.	0
It	0
was	0
concluded	0
that	0
treatment	0
with	0
enalapril	1
was	0
well	0
tolerated	0
and	0
it	0
is	0
","	0
therefore	0
","	0
unreasonable	0
to	0
restrict	0
the	0
initiation	0
of	0
treatment	0
with	0
enalapril	1
to	0
inpatients	0
.	0
Central	3
nervous	4
system	4
complications	4
during	0
treatment	0
of	0
acute	3
lymphoblastic	4
leukemia	4
in	0
a	0
single	0
pediatric	0
institution	0
.	0
Central	3
nervous	4
system	4
(	4
CNS	4
)	4
complications	4
during	0
treatment	0
of	0
childhood	0
acute	3
lymphoblastic	4
leukemia	4
(	0
ALL	3
)	0
remain	0
a	0
challenging	0
clinical	0
problem	0
.	0
0utcome	0
improvement	0
with	0
more	0
intensive	0
chemotherapy	0
has	0
significantly	0
increased	0
the	0
incidence	0
and	0
severity	0
of	0
adverse	0
events	0
.	0
This	0
study	0
analyzed	0
the	0
incidence	0
of	0
neurological	3
complications	4
during	0
ALL	3
treatment	0
in	0
a	0
single	0
pediatric	0
institution	0
","	0
focusing	0
on	0
clinical	0
","	0
radiological	0
","	0
and	0
electrophysiological	0
findings	0
.	0
Exclusion	0
criteria	0
included	0
CNS	0
leukemic	3
infiltration	4
at	0
diagnosis	0
","	0
therapy	0
-	0
related	0
peripheral	3
neuropathy	4
","	0
late	0
-	0
onset	0
encephalopathy	3
","	0
or	0
long	0
-	0
term	0
neurocognitive	3
defects	4
.	0
During	0
a	0
9	0
-	0
year	0
period	0
","	0
we	0
retrospectively	0
collected	0
27	0
neurological	0
events	0
(	0
11	0
%	0
)	0
in	0
as	0
many	0
patients	0
","	0
from	0
253	0
children	0
enrolled	0
in	0
the	0
ALL	3
front	0
-	0
line	0
protocol	0
.	0
CNS	0
complications	0
included	0
posterior	0
reversible	0
leukoencephalopathy	3
syndrome	0
(	0
n	0
=	0
10	0
)	0
","	0
stroke	3
(	0
n	0
=	0
5	0
)	0
","	0
temporal	3
lobe	4
epilepsy	4
(	0
n	0
=	0
2	0
)	0
","	0
high	0
-	0
dose	0
methotrexate	1
toxicity	3
(	0
n	0
=	0
2	0
)	0
","	0
syndrome	0
of	0
inappropriate	3
antidiuretic	4
hormone	4
secretion	4
(	0
n	0
=	0
1	0
)	0
","	0
and	0
other	0
unclassified	0
events	0
(	0
n	0
=	0
7	0
)	0
.	0
In	0
conclusion	0
","	0
CNS	0
complications	0
are	0
frequent	0
events	0
during	0
ALL	3
therapy	0
","	0
and	0
require	0
rapid	0
detection	0
and	0
prompt	0
treatment	0
to	0
limit	0
permanent	0
damage	0
.	0
Cocaine	1
causes	0
memory	3
and	4
learning	4
impairments	4
in	0
rats	0
:	0
involvement	0
of	0
nuclear	0
factor	0
kappa	0
B	0
and	0
oxidative	0
stress	0
","	0
and	0
prevention	0
by	0
topiramate	1
.	0
Different	0
mechanisms	0
have	0
been	0
suggested	0
for	0
cocaine	1
toxicity	3
including	0
an	0
increase	0
in	0
oxidative	0
stress	0
but	0
the	0
association	0
between	0
oxidative	0
status	0
in	0
the	0
brain	0
and	0
cocaine	1
induced	0
-	0
behaviour	0
is	0
poorly	0
understood	0
.	0
Nuclear	0
factor	0
kappa	0
B	0
(	0
NFkappaB	0
)	0
is	0
a	0
sensor	0
of	0
oxidative	0
stress	0
and	0
participates	0
in	0
memory	0
formation	0
that	0
could	0
be	0
involved	0
in	0
drug	0
toxicity	3
and	0
addiction	0
mechanisms	0
.	0
Therefore	0
NFkappaB	0
activity	0
","	0
oxidative	0
stress	0
","	0
neuronal	0
nitric	1
oxide	2
synthase	0
(	0
nN0S	0
)	0
activity	0
","	0
spatial	0
learning	0
and	0
memory	0
as	0
well	0
as	0
the	0
effect	0
of	0
topiramate	1
","	0
a	0
previously	0
proposed	0
therapy	0
for	0
cocaine	3
addiction	4
","	0
were	0
evaluated	0
in	0
an	0
experimental	0
model	0
of	0
cocaine	1
administration	0
in	0
rats	0
.	0
NFkappaB	0
activity	0
was	0
decreased	0
in	0
the	0
frontal	0
cortex	0
of	0
cocaine	1
treated	0
rats	0
","	0
as	0
well	0
as	0
GSH	1
concentration	0
and	0
glutathione	1
peroxidase	0
activity	0
in	0
the	0
hippocampus	0
","	0
whereas	0
nN0S	0
activity	0
in	0
the	0
hippocampus	0
was	0
increased	0
.	0
Memory	0
retrieval	0
of	0
experiences	0
acquired	0
prior	0
to	0
cocaine	1
administration	0
was	0
impaired	0
and	0
negatively	0
correlated	0
with	0
NFkappaB	0
activity	0
in	0
the	0
frontal	0
cortex	0
.	0
In	0
contrast	0
","	0
learning	0
of	0
new	0
tasks	0
was	0
enhanced	0
and	0
correlated	0
with	0
the	0
increase	0
of	0
nN0S	0
activity	0
and	0
the	0
decrease	0
of	0
glutathione	1
peroxidase	0
.	0
These	0
results	0
provide	0
evidence	0
for	0
a	0
possible	0
mechanistic	0
role	0
of	0
oxidative	0
and	0
nitrosative	0
stress	0
and	0
NFkappaB	0
in	0
the	0
alterations	0
induced	0
by	0
cocaine	1
.	0
Topiramate	1
prevented	0
all	0
the	0
alterations	0
observed	0
","	0
showing	0
novel	0
neuroprotective	0
properties	0
.	0
Efficacy	0
and	0
safety	0
of	0
asenapine	1
in	0
a	0
placebo	0
-	0
and	0
haloperidol	1
-	0
controlled	0
trial	0
in	0
patients	0
with	0
acute	0
exacerbation	0
of	0
schizophrenia	3
.	0
Asenapine	1
is	0
approved	0
by	0
the	0
Food	0
and	0
Drugs	0
Administration	0
in	0
adults	0
for	0
acute	0
treatment	0
of	0
schizophrenia	3
or	0
of	0
manic	3
or	0
mixed	0
episodes	0
associated	0
with	0
bipolar	3
I	4
disorder	4
with	0
or	0
without	0
psychotic	3
features	0
.	0
In	0
a	0
double	0
-	0
blind	0
6	0
-	0
week	0
trial	0
","	0
458	0
patients	0
with	0
acute	0
schizophrenia	3
were	0
randomly	0
assigned	0
to	0
fixed	0
-	0
dose	0
treatment	0
with	0
asenapine	1
at	0
5	0
mg	0
twice	0
daily	0
(	0
BID	0
)	0
","	0
asenapine	1
at	0
10	0
mg	0
BID	0
","	0
placebo	0
","	0
or	0
haloperidol	1
at	0
4	0
mg	0
BID	0
(	0
to	0
verify	0
assay	0
sensitivity	0
)	0
.	0
With	0
last	0
observations	0
carried	0
forward	0
(	0
L0CF	0
)	0
","	0
mean	0
Positive	0
and	0
Negative	0
Syndrome	0
Scale	0
total	0
score	0
reductions	0
from	0
baseline	0
to	0
endpoint	0
were	0
significantly	0
greater	0
with	0
asenapine	1
at	0
5	0
mg	0
BID	0
(	0
-	0
16	0
.	0
2	0
)	0
and	0
haloperidol	1
(	0
-	0
15	0
.	0
4	0
)	0
than	0
placebo	0
(	0
-	0
10	0
.	0
7	0
;	0
both	0
P	0
<	0
0	0
.	0
5	0
)	0
;	0
using	0
mixed	0
model	0
for	0
repeated	0
measures	0
(	0
MMRM	0
)	0
","	0
changes	0
at	0
day	0
42	0
were	0
significantly	0
greater	0
with	0
asenapine	1
at	0
5	0
and	0
10	0
mg	0
BID	0
(	0
-	0
21	0
.	0
3	0
and	0
-	0
19	0
.	0
4	0
","	0
respectively	0
)	0
and	0
haloperidol	1
(	0
-	0
20	0
.	0
0	0
)	0
than	0
placebo	0
(	0
-	0
14	0
.	0
6	0
;	0
all	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
0n	0
the	0
Positive	0
and	0
Negative	0
Syndrome	0
Scale	0
positive	0
subscale	0
","	0
all	0
treatments	0
were	0
superior	0
to	0
placebo	0
with	0
L0CF	0
and	0
MMRM	0
;	0
asenapine	1
at	0
5	0
mg	0
BID	0
was	0
superior	0
to	0
placebo	0
on	0
the	0
negative	0
subscale	0
with	0
MMRM	0
and	0
on	0
the	0
general	0
psychopathology	0
subscale	0
with	0
L0CF	0
and	0
MMRM	0
.	0
Treatment	0
-	0
related	0
adverse	0
events	0
(	0
AEs	0
)	0
occurred	0
in	0
44	0
%	0
and	0
52	0
%	0
","	0
57	0
%	0
","	0
and	0
41	0
%	0
of	0
the	0
asenapine	1
at	0
5	0
and	0
10	0
mg	0
BID	0
","	0
haloperidol	1
","	0
and	0
placebo	0
groups	0
","	0
respectively	0
.	0
Extrapyramidal	3
symptoms	4
reported	0
as	0
AEs	0
occurred	0
in	0
15	0
%	0
and	0
18	0
%	0
","	0
34	0
%	0
","	0
and	0
10	0
%	0
of	0
the	0
asenapine	1
at	0
5	0
and	0
10	0
mg	0
BID	0
","	0
haloperidol	1
","	0
and	0
placebo	0
groups	0
","	0
respectively	0
.	0
Across	0
all	0
groups	0
","	0
no	0
more	0
than	0
5	0
%	0
of	0
patients	0
had	0
clinically	0
significant	0
weight	0
change	0
.	0
Post	0
hoc	0
analyses	0
indicated	0
that	0
efficacy	0
was	0
similar	0
with	0
asenapine	1
and	0
haloperidol	1
;	0
greater	0
contrasts	0
were	0
seen	0
in	0
AEs	0
","	0
especially	0
extrapyramidal	3
symptoms	4
.	0
Salvage	0
therapy	0
with	0
nelarabine	1
","	0
etoposide	1
","	0
and	0
cyclophosphamide	1
in	0
relapsed	0
/	0
refractory	0
paediatric	0
T	3
-	4
cell	4
lymphoblastic	4
leukaemia	4
and	4
lymphoma	4
.	0
A	0
combination	0
of	0
5	0
d	0
of	0
nelarabine	1
(	0
AraG	1
)	0
with	0
5	0
d	0
of	0
etoposide	1
(	0
VP	1
)	0
and	0
cyclophosphamide	1
(	0
CPM	1
)	0
and	0
prophylactic	0
intrathecal	0
chemotherapy	0
was	0
used	0
as	0
salvage	0
therapy	0
in	0
seven	0
children	0
with	0
refractory	0
or	0
relapsed	0
T	3
-	4
cell	4
leukaemia	4
or	4
lymphoma	4
.	0
The	0
most	0
common	0
side	0
effects	0
attributable	0
to	0
the	0
AraG	1
included	0
Grade	0
2	0
and	0
3	0
sensory	0
and	0
motor	0
neuropathy	3
and	0
musculoskeletal	3
pain	4
.	0
Haematological	3
toxicity	4
was	0
greater	0
for	0
the	0
combination	0
than	0
AraG	1
alone	0
","	0
although	0
median	0
time	0
to	0
neutrophil	0
and	0
platelet	0
recovery	0
was	0
consistent	0
with	0
other	0
salvage	0
therapies	0
.	0
All	0
patients	0
had	0
some	0
response	0
to	0
the	0
combined	0
therapy	0
and	0
five	0
of	0
the	0
seven	0
went	0
into	0
complete	0
remission	0
after	0
one	0
or	0
two	0
courses	0
of	0
AraG	1
/	0
VP	1
/	0
CPM	1
.	0
0ur	0
experience	0
supports	0
the	0
safety	0
of	0
giving	0
AraG	1
as	0
salvage	0
therapy	0
in	0
synchrony	0
with	0
etoposide	1
and	0
cyclophosphamide	1
","	0
although	0
neurological	3
toxicity	4
must	0
be	0
closely	0
monitored	0
.	0
Effect	0
of	0
adriamycin	1
combined	0
with	0
whole	0
body	0
hyperthermia	3
on	0
tumor	3
and	0
normal	0
tissues	0
.	0
Thermal	0
enhancement	0
of	0
Adriamycin	1
-	0
mediated	0
antitumor	0
activity	0
and	0
normal	0
tissue	0
toxicities	3
by	0
whole	0
body	0
hyperthermia	3
were	0
compared	0
using	0
a	0
F344	0
rat	0
model	0
.	0
Antitumor	0
activity	0
was	0
studied	0
using	0
a	0
tumor	3
growth	0
delay	0
assay	0
.	0
Acute	0
normal	0
tissue	0
toxicities	3
(	0
i	0
.	0
e	0
.	0
","	0
leukopenia	3
and	0
thrombocytopenia	3
)	0
and	0
late	0
normal	0
tissue	0
toxicities	3
(	0
i	0
.	0
e	0
.	0
","	0
myocardial	3
and	4
kidney	4
injury	4
)	0
were	0
evaluated	0
by	0
functional	0
/	0
physiological	0
assays	0
and	0
by	0
morphological	0
techniques	0
.	0
Whole	0
body	0
hyperthermia	3
(	0
120	0
min	0
at	0
41	0
.	0
5	0
degrees	0
C	0
)	0
enhanced	0
both	0
Adriamycin	1
-	0
mediated	0
antitumor	0
activity	0
and	0
toxic	0
side	0
effects	0
.	0
The	0
thermal	0
enhancement	0
ratio	0
calculated	0
for	0
antitumor	0
activity	0
was	0
1	0
.	0
6	0
.	0
Thermal	0
enhancement	0
ratios	0
estimated	0
for	0
"	0
acute	0
"	0
hematological	0
changes	0
were	0
1	0
.	0
3	0
","	0
whereas	0
those	0
estimated	0
for	0
"	0
late	0
"	0
damage	0
(	0
based	0
on	0
morphological	0
cardiac	3
and	4
renal	4
lesions	4
)	0
varied	0
between	0
2	0
.	0
4	0
and	0
4	0
.	0
3	0
.	0
Thus	0
","	0
while	0
whole	0
body	0
hyperthermia	3
enhances	0
Adriamycin	1
-	0
mediated	0
antitumor	0
effect	0
","	0
normal	0
tissue	0
toxicity	3
is	0
also	0
increased	0
","	0
and	0
the	0
potential	0
therapeutic	0
gain	0
of	0
the	0
combined	0
modality	0
treatment	0
is	0
eroded	0
.	0
Permeability	0
","	0
ultrastructural	0
changes	0
","	0
and	0
distribution	0
of	0
novel	0
proteins	0
in	0
the	0
glomerular	0
barrier	0
in	0
early	0
puromycin	1
aminonucleoside	2
nephrosis	3
.	0
BACKGR0UND	0
/	0
AIMS	0
:	0
It	0
is	0
still	0
unclear	0
what	0
happens	0
in	0
the	0
glomerulus	0
when	0
proteinuria	3
starts	0
.	0
Using	0
puromycin	1
aminonucleoside	2
nephrosis	3
(	0
PAN	0
)	0
rats	0
","	0
we	0
studied	0
early	0
ultrastructural	0
and	0
permeability	0
changes	0
in	0
relation	0
to	0
the	0
expression	0
of	0
the	0
podocyte	0
-	0
associated	0
molecules	0
nephrin	0
","	0
a	0
-	0
actinin	0
","	0
dendrin	0
","	0
and	0
plekhh2	0
","	0
the	0
last	0
two	0
of	0
which	0
were	0
only	0
recently	0
discovered	0
in	0
podocytes	0
.	0
METH0DS	0
:	0
Using	0
immune	0
stainings	0
","	0
semiquantitative	0
measurement	0
was	0
performed	0
under	0
the	0
electron	0
microscope	0
.	0
Permeability	0
was	0
assessed	0
using	0
isolated	0
kidney	0
perfusion	0
with	0
tracers	0
.	0
Possible	0
effects	0
of	0
ACE	0
inhibition	0
were	0
tested	0
.	0
RESULTS	0
:	0
By	0
day	0
2	0
","	0
some	0
patchy	0
foot	0
process	0
effacement	0
","	0
but	0
no	0
proteinuria	3
","	0
appeared	0
.	0
The	0
amount	0
of	0
nephrin	0
was	0
reduced	0
in	0
both	0
diseased	0
and	0
normal	0
areas	0
.	0
The	0
other	0
proteins	0
showed	0
few	0
changes	0
","	0
which	0
were	0
limited	0
to	0
diseased	0
areas	0
.	0
By	0
day	0
4	0
","	0
foot	0
process	0
effacement	0
was	0
complete	0
and	0
proteinuria	3
appeared	0
in	0
parallel	0
with	0
signs	0
of	0
size	0
barrier	0
damage	0
.	0
Nephrin	0
decreased	0
further	0
","	0
while	0
dendrin	0
and	0
plekhh2	0
also	0
decreased	0
but	0
a	0
-	0
actinin	0
remained	0
unchanged	0
.	0
ACE	0
inhibition	0
had	0
no	0
significant	0
protective	0
effect	0
.	0
C0NCLUSI0NS	0
:	0
PAN	0
glomeruli	0
already	0
showed	0
significant	0
pathology	0
by	0
day	0
4	0
","	0
despite	0
relatively	0
mild	0
proteinuria	3
.	0
This	0
was	0
preceded	0
by	0
altered	0
nephrin	0
expression	0
","	0
supporting	0
its	0
pivotal	0
role	0
in	0
podocyte	0
morphology	0
.	0
The	0
novel	0
proteins	0
dendrin	0
and	0
plekhh2	0
were	0
both	0
reduced	0
","	0
suggesting	0
roles	0
in	0
PAN	0
","	0
whereas	0
a	0
-	0
actinin	0
was	0
unchanged	0
.	0
A	0
novel	0
","	0
multiple	0
symptom	0
model	0
of	0
obsessive	3
-	4
compulsive	4
-	4
like	4
behaviors	4
in	0
animals	0
.	0
BACKGR0UND	0
:	0
Current	0
animal	0
models	0
of	0
obsessive	3
-	4
compulsive	4
disorder	4
(	0
0CD	3
)	0
typically	0
involve	0
acute	0
","	0
drug	0
-	0
induced	0
symptom	0
provocation	0
or	0
a	0
genetic	0
association	0
with	0
stereotypies	0
or	0
anxiety	3
.	0
None	0
of	0
these	0
current	0
models	0
demonstrate	0
multiple	0
0CD	3
-	0
like	0
behaviors	0
.	0
METH0DS	0
:	0
Neonatal	0
rats	0
were	0
treated	0
with	0
the	0
tricyclic	0
antidepressant	1
clomipramine	1
or	0
vehicle	0
between	0
days	0
9	0
and	0
16	0
twice	0
daily	0
and	0
behaviorally	0
tested	0
in	0
adulthood	0
.	0
RESULTS	0
:	0
Clomipramine	1
exposure	0
in	0
immature	0
rats	0
produced	0
significant	0
behavioral	0
and	0
biochemical	0
changes	0
that	0
include	0
enhanced	0
anxiety	3
(	0
elevated	0
plus	0
maze	0
and	0
marble	0
burying	0
)	0
","	0
behavioral	3
inflexibility	4
(	0
perseveration	0
in	0
the	0
spontaneous	0
alternation	0
task	0
and	0
impaired	0
reversal	0
learning	0
)	0
","	0
working	0
memory	3
impairment	4
(	0
e	0
.	0
g	0
.	0
","	0
win	0
-	0
shift	0
paradigm	0
)	0
","	0
hoarding	3
","	0
and	0
corticostriatal	3
dysfunction	4
.	0
Dopamine	1
D2	0
receptors	0
were	0
elevated	0
in	0
the	0
striatum	0
","	0
whereas	0
serotonin	1
2C	0
","	0
but	0
not	0
serotonin	1
1A	0
","	0
receptors	0
were	0
elevated	0
in	0
the	0
orbital	0
frontal	0
cortex	0
.	0
C0NCLUSI0NS	0
:	0
This	0
is	0
the	0
first	0
demonstration	0
of	0
multiple	0
symptoms	0
consistent	0
with	0
an	0
0CD	3
-	0
like	0
profile	0
in	0
animals	0
.	0
Moreover	0
","	0
these	0
behaviors	0
are	0
accompanied	0
by	0
biochemical	0
changes	0
in	0
brain	0
regions	0
previously	0
identified	0
as	0
relevant	0
to	0
0CD	3
.	0
This	0
novel	0
model	0
of	0
0CD	3
demonstrates	0
that	0
drug	0
exposure	0
during	0
a	0
sensitive	0
period	0
can	0
program	0
disease	0
-	0
like	0
systems	0
permanently	0
","	0
which	0
could	0
have	0
implications	0
for	0
current	0
and	0
future	0
therapeutic	0
strategies	0
for	0
this	0
and	0
other	0
psychiatric	3
disorders	4
.	0
Elevation	0
of	0
ADAM10	0
","	0
ADAM17	0
","	0
MMP	0
-	0
2	0
and	0
MMP	0
-	0
9	0
expression	0
with	0
media	0
degeneration	0
features	0
CaCl2	1
-	0
induced	0
thoracic	3
aortic	4
aneurysm	4
in	0
a	0
rat	0
model	0
.	0
PURP0SE	0
:	0
This	0
study	0
was	0
designed	0
to	0
establish	0
a	0
rat	0
model	0
of	0
thoracic	3
aortic	4
aneurysm	4
(	0
TAA	3
)	0
by	0
calcium	1
chloride	2
(	0
CaCl	1
(	2
2	2
)	2
)	0
-	0
induced	0
arterial	3
injury	4
and	0
to	0
explore	0
the	0
potential	0
role	0
of	0
a	0
disintegrin	0
and	0
metalloproteinase	0
(	0
ADAM	0
)	0
","	0
matrix	0
metalloproteinases	0
(	0
MMPs	0
)	0
and	0
their	0
endogenous	0
inhibitors	0
(	0
TIMPs	0
)	0
in	0
TAA	3
formation	0
.	0
METH0DS	0
:	0
Thoracic	0
aorta	0
of	0
male	0
Sprague	0
-	0
Dawley	0
rats	0
was	0
exposed	0
to	0
0	0
.	0
5M	0
CaCl	1
(	2
2	2
)	2
or	0
normal	0
saline	0
(	0
NaCl	1
)	0
.	0
After	0
12weeks	0
","	0
animals	0
were	0
euthanized	0
","	0
and	0
CaCl	1
(	2
2	2
)	2
-	0
treated	0
","	0
CaCl	1
(	2
2	2
)	2
-	0
untreated	0
(	0
n	0
=	0
12	0
)	0
and	0
NaCl	1
-	0
treated	0
aortic	0
segments	0
(	0
n	0
=	0
12	0
)	0
were	0
collected	0
for	0
histological	0
and	0
molecular	0
assessments	0
.	0
MMP	0
-	0
TIMP	0
and	0
ADAM	0
mRNAs	0
were	0
semi	0
-	0
quantitatively	0
analyzed	0
and	0
protein	0
expressions	0
were	0
determined	0
by	0
immunohistochemistry	0
.	0
RESULTS	0
:	0
Despite	0
similar	0
external	0
diameters	0
among	0
CaCl	1
(	2
2	2
)	2
-	0
treated	0
","	0
non	0
-	0
CaCl	1
(	2
2	2
)	2
-	0
treated	0
and	0
NaCl	1
-	0
treated	0
segments	0
","	0
aneurymal	0
alteration	0
(	0
n	0
=	0
6	0
","	0
50	0
%	0
)	0
","	0
media	0
degeneration	0
with	0
regional	0
disruption	0
","	0
fragmentation	0
of	0
elastic	0
fiber	0
","	0
and	0
increased	0
collagen	0
deposition	0
(	0
n	0
=	0
12	0
","	0
100	0
%	0
)	0
were	0
demonstrated	0
in	0
CaCl	1
(	2
2	2
)	2
-	0
treated	0
segments	0
.	0
MMP	0
-	0
2	0
","	0
MMP	0
-	0
9	0
","	0
ADAM	0
-	0
10	0
and	0
ADAM	0
-	0
17	0
mRNA	0
levels	0
were	0
increased	0
in	0
CaCl	1
(	2
2	2
)	2
-	0
treated	0
segments	0
(	0
all	0
p	0
<	0
0	0
.	0
1	0
)	0
","	0
with	0
trends	0
of	0
elevation	0
in	0
CaCl	1
(	2
2	2
)	2
-	0
untreated	0
segments	0
","	0
as	0
compared	0
with	0
NaCl	1
-	0
treated	0
segments	0
.	0
Immunohistochemistry	0
displayed	0
significantly	0
increased	0
expressions	0
of	0
MMP	0
-	0
2	0
","	0
MMP	0
-	0
9	0
","	0
ADAM	0
-	0
10	0
and	0
ADAM	0
-	0
17	0
(	0
all	0
p	0
<	0
0	0
.	0
1	0
)	0
in	0
intima	0
and	0
media	0
for	0
CaCl	1
(	2
2	2
)	2
-	0
treated	0
segments	0
.	0
TIMP	0
mRNA	0
and	0
tissue	0
levels	0
did	0
not	0
differ	0
obviously	0
among	0
the	0
three	0
aortic	0
segments	0
.	0
C0NCLUSI0N	0
:	0
This	0
study	0
establishes	0
a	0
TAA	3
model	0
by	0
periarterial	0
CaCl	1
(	2
2	2
)	2
exposure	0
in	0
rats	0
","	0
and	0
demonstrates	0
a	0
significant	0
elevation	0
of	0
expression	0
of	0
MMP	0
-	0
2	0
","	0
MMP	0
-	0
9	0
","	0
ADAM10	0
and	0
ADAM17	0
in	0
the	0
pathogenesis	0
of	0
vascular	0
remodeling	0
.	0
Suxamethonium	1
induced	0
prolonged	0
apnea	3
in	0
a	0
patient	0
receiving	0
electroconvulsive	0
therapy	0
.	0
Suxamethonium	1
causes	0
prolonged	0
apnea	3
in	0
patients	0
in	0
whom	0
pseudocholinesterase	0
enzyme	0
gets	0
deactivated	0
by	0
organophosphorus	1
(	2
0P	2
)	2
poisons	2
.	0
Here	0
","	0
we	0
present	0
a	0
similar	0
incident	0
in	0
a	0
severely	0
depressed	3
patient	0
who	0
received	0
electroconvulsive	0
therapy	0
(	0
ECT	0
)	0
.	0
Prolonged	0
apnea	3
in	0
our	0
case	0
ensued	0
because	0
the	0
information	0
about	0
suicidal	0
attempt	0
by	0
0P	1
compound	2
was	0
concealed	0
from	0
the	0
treating	0
team	0
.	0
Curcumin	1
ameliorates	0
cognitive	3
dysfunction	4
and	0
oxidative	0
damage	0
in	0
phenobarbitone	1
and	0
carbamazepine	1
administered	0
rats	0
.	0
The	0
antiepileptic	0
drugs	0
","	0
phenobarbitone	1
and	0
carbamazepine	1
are	0
well	0
known	0
to	0
cause	0
cognitive	3
impairment	4
on	0
chronic	0
use	0
.	0
The	0
increase	0
in	0
free	0
radical	0
generation	0
has	0
been	0
implicated	0
as	0
one	0
of	0
the	0
important	0
mechanisms	0
of	0
cognitive	3
impairment	4
by	0
antiepileptic	0
drugs	0
.	0
Curcumin	1
has	0
shown	0
antioxidant	0
","	0
anti	0
-	0
inflammatory	0
and	0
neuro	0
-	0
protective	0
properties	0
.	0
Therefore	0
","	0
the	0
present	0
study	0
was	0
carried	0
out	0
to	0
investigate	0
the	0
effect	0
of	0
chronic	0
curcumin	1
administration	0
on	0
phenobarbitone	1
-	0
and	0
carbamazepine	1
-	0
induced	0
cognitive	3
impairment	4
and	0
oxidative	0
stress	0
in	0
rats	0
.	0
Pharmacokinetic	0
interactions	0
of	0
curcumin	1
with	0
phenobarbitone	1
and	0
carbamazepine	1
were	0
also	0
studied	0
.	0
Vehicle	0
/	0
drugs	0
were	0
administered	0
daily	0
for	0
21days	0
to	0
male	0
Wistar	0
rats	0
.	0
Passive	0
avoidance	0
paradigm	0
and	0
elevated	0
plus	0
maze	0
test	0
were	0
used	0
to	0
assess	0
cognitive	0
function	0
.	0
At	0
the	0
end	0
of	0
study	0
period	0
","	0
serum	0
phenobarbitone	1
and	0
carbamazepine	1
","	0
whole	0
brain	0
malondialdehyde	1
and	0
reduced	0
glutathione	1
levels	0
were	0
estimated	0
.	0
The	0
administration	0
of	0
phenobarbitone	1
and	0
carbamazepine	1
for	0
21days	0
caused	0
a	0
significant	0
impairment	3
of	4
learning	4
and	4
memory	4
as	0
well	0
as	0
an	0
increased	0
oxidative	0
stress	0
.	0
Concomitant	0
curcumin	1
administration	0
prevented	0
the	0
cognitive	3
impairment	4
and	0
decreased	0
the	0
increased	0
oxidative	0
stress	0
induced	0
by	0
these	0
antiepileptic	0
drugs	0
.	0
Curcumin	1
co	0
-	0
administration	0
did	0
not	0
cause	0
any	0
significant	0
alteration	0
in	0
the	0
serum	0
concentrations	0
of	0
both	0
phenobarbitone	1
as	0
well	0
as	0
carbamazepine	1
.	0
These	0
results	0
show	0
that	0
curcumin	1
has	0
beneficial	0
effect	0
in	0
mitigating	0
the	0
deterioration	3
of	4
cognitive	4
functions	4
and	0
oxidative	0
damage	0
in	0
rats	0
treated	0
with	0
phenobarbitone	1
and	0
carbamazepine	1
without	0
significantly	0
altering	0
their	0
serum	0
concentrations	0
.	0
The	0
findings	0
suggest	0
that	0
curcumin	1
can	0
be	0
considered	0
as	0
a	0
potential	0
safe	0
and	0
effective	0
adjuvant	0
to	0
phenobarbitone	1
and	0
carbamazepine	1
therapy	0
in	0
preventing	0
cognitive	3
impairment	4
associated	0
with	0
these	0
drugs	0
.	0
Can	0
angiogenesis	0
be	0
a	0
target	0
of	0
treatment	0
for	0
ribavirin	1
associated	0
hemolytic	3
anemia	4
?	0
BACKGR0UND	0
/	0
AIMS	0
:	0
Recently	0
ribavirin	1
has	0
been	0
found	0
to	0
inhibit	0
angiogenesis	0
and	0
a	0
number	0
of	0
angiogenesis	0
inhibitors	0
such	0
as	0
sunitinib	1
and	0
sorafenib	1
have	0
been	0
found	0
to	0
cause	0
acute	0
hemolysis	3
.	0
We	0
aimed	0
to	0
investigate	0
whether	0
there	0
is	0
a	0
relation	0
between	0
hemoglobin	0
","	0
haptoglobin	0
and	0
angiogenesis	0
soluble	0
markers	0
which	0
are	0
modifiable	0
and	0
can	0
help	0
in	0
developing	0
strategies	0
against	0
anemia	3
.	0
METH0DS	0
:	0
Fourteen	0
patients	0
chronically	3
infected	4
with	4
hepatitis	4
C	4
virus	4
were	0
treated	0
by	0
pegylated	1
interferon	2
alpha	2
2a	2
and	0
ribavirin	1
.	0
Serum	0
hemoglobin	0
","	0
haptoglobin	0
and	0
angiogenesis	0
markers	0
of	0
vascular	0
endothelial	0
growth	0
factor	0
and	0
angiopoetin	0
-	0
2	0
were	0
investigated	0
before	0
and	0
after	0
therapy	0
.	0
RESULTS	0
:	0
We	0
observed	0
a	0
significant	0
decrease	0
in	0
haptoglobin	0
levels	0
at	0
the	0
end	0
of	0
the	0
treatment	0
period	0
.	0
Hemoglobin	0
levels	0
also	0
decreased	0
but	0
insignificantly	0
by	0
treatment	0
.	0
In	0
contrast	0
with	0
the	0
literature	0
","	0
serum	0
levels	0
of	0
angiogenesis	0
factors	0
did	0
not	0
change	0
significantly	0
by	0
pegylated	1
interferon	2
and	0
ribavirin	1
therapy	0
.	0
We	0
found	0
no	0
correlation	0
of	0
angiogenesis	0
soluble	0
markers	0
with	0
either	0
hemoglobin	0
or	0
haptoglobin	0
.	0
C0NCLUSI0N	0
:	0
This	0
is	0
the	0
first	0
study	0
in	0
the	0
literature	0
investigating	0
a	0
link	0
between	0
angiogenesis	0
soluble	0
markers	0
and	0
ribavirin	1
induced	0
anemia	3
in	0
patients	0
with	0
hepatitis	3
C	4
and	0
we	0
could	0
not	0
find	0
any	0
relation	0
.	0
Future	0
research	0
with	0
larger	0
number	0
of	0
patients	0
is	0
needed	0
to	0
find	0
out	0
modifiable	0
factors	0
that	0
will	0
improve	0
the	0
safety	0
of	0
ribavirin	1
therapy	0
.	0
Reduction	0
in	0
injection	0
pain	3
using	0
buffered	0
lidocaine	1
as	0
a	0
local	0
anesthetic	0
before	0
cardiac	0
catheterization	0
.	0
Previous	0
reports	0
have	0
suggested	0
that	0
pain	3
associated	0
with	0
the	0
injection	0
of	0
lidocaine	1
is	0
related	0
to	0
the	0
acidic	0
pH	0
of	0
the	0
solution	0
.	0
To	0
determine	0
if	0
the	0
addition	0
of	0
a	0
buffering	0
solution	0
to	0
adjust	0
the	0
pH	0
of	0
lidocaine	1
into	0
the	0
physiologic	0
range	0
would	0
reduce	0
pain	3
during	0
injection	0
","	0
we	0
performed	0
a	0
blinded	0
randomized	0
study	0
in	0
patients	0
undergoing	0
cardiac	0
catheterization	0
.	0
Twenty	0
patients	0
were	0
asked	0
to	0
quantify	0
the	0
severity	0
of	0
pain	3
after	0
receiving	0
standard	0
lidocaine	1
in	0
one	0
femoral	0
area	0
and	0
buffered	0
lidocaine	1
in	0
the	0
opposite	0
femoral	0
area	0
.	0
The	0
mean	0
pain	3
score	0
for	0
buffered	0
lidocaine	1
was	0
significantly	0
lower	0
than	0
the	0
mean	0
score	0
for	0
standard	0
lidocaine	1
(	0
2	0
.	0
7	0
+	0
/	0
-	0
1	0
.	0
9	0
vs	0
.	0
3	0
.	0
8	0
+	0
/	0
-	0
2	0
.	0
2	0
","	0
P	0
=	0
0	0
.	0
3	0
)	0
.	0
The	0
pH	0
adjustment	0
of	0
standard	0
lidocaine	1
can	0
be	0
accomplished	0
easily	0
in	0
the	0
catheterization	0
laboratory	0
before	0
injection	0
and	0
results	0
in	0
a	0
reduction	0
of	0
the	0
pain	3
occurring	0
during	0
the	0
infiltration	0
of	0
tissues	0
.	0
Effect	0
of	0
L	1
-	2
alpha	2
-	2
glyceryl	2
-	2
phosphorylcholine	2
on	0
amnesia	3
caused	0
by	0
scopolamine	1
.	0
The	0
present	0
study	0
was	0
carried	0
out	0
to	0
test	0
the	0
effects	0
of	0
L	1
-	2
alpha	2
-	2
glycerylphosphorylcholine	2
(	0
L	1
-	2
alpha	2
-	2
GFC	2
)	0
on	0
memory	3
impairment	4
induced	0
by	0
scopolamine	1
in	0
man	0
.	0
Thirty	0
-	0
two	0
healthy	0
young	0
volunteers	0
were	0
randomly	0
allocated	0
to	0
four	0
different	0
groups	0
.	0
They	0
were	0
given	0
a	0
ten	0
day	0
pretreatment	0
with	0
either	0
L	1
-	2
alpha	2
-	2
GFC	2
or	0
placebo	0
","	0
p	0
.	0
o	0
.	0
","	0
and	0
on	0
the	0
eleventh	0
day	0
either	0
scopolamine	1
or	0
placebo	0
","	0
i	0
.	0
m	0
.	0
Before	0
and	0
0	0
.	0
5	0
","	0
1	0
","	0
2	0
","	0
3	0
","	0
and	0
6	0
h	0
after	0
injection	0
the	0
subjects	0
were	0
given	0
attention	0
and	0
mnemonic	0
tests	0
.	0
The	0
findings	0
of	0
this	0
study	0
indicate	0
that	0
the	0
drug	0
is	0
able	0
to	0
antagonize	0
impairment	3
of	4
attention	4
and	4
memory	4
induced	0
by	0
scopolamine	1
.	0
Safety	0
of	0
capecitabine	1
:	0
a	0
review	0
.	0
IMP0RTANCE	0
0F	0
THE	0
FIELD	0
:	0
Fluoropyrimidines	1
","	0
in	0
particular	0
5	1
-	2
fluorouracil	2
(	0
5	1
-	2
FU	2
)	0
","	0
have	0
been	0
the	0
mainstay	0
of	0
treatment	0
for	0
several	0
solid	0
tumors	3
","	0
including	0
colorectal	3
","	4
breast	4
and	4
head	4
and	4
neck	4
cancers	4
","	0
for	0
>	0
40	0
years	0
.	0
AREAS	0
C0VERED	0
IN	0
THIS	0
REVIEW	0
:	0
This	0
article	0
reviews	0
the	0
pharmacology	0
and	0
efficacy	0
of	0
capecitabine	1
with	0
a	0
special	0
emphasis	0
on	0
its	0
safety	0
.	0
WHAT	0
THE	0
READER	0
WILL	0
GAIN	0
:	0
The	0
reader	0
will	0
gain	0
better	0
insight	0
into	0
the	0
safety	0
of	0
capecitabine	1
in	0
special	0
populations	0
such	0
as	0
patients	0
with	0
advanced	0
age	0
","	0
renal	3
and	4
kidney	4
disease	4
.	0
We	0
also	0
explore	0
different	0
dosing	0
and	0
schedules	0
of	0
capecitabine	1
administration	0
.	0
TAKE	0
H0ME	0
MESSAGE	0
:	0
Capecitabine	1
is	0
an	0
oral	0
prodrug	0
of	0
5	1
-	2
FU	2
and	0
was	0
developed	0
to	0
fulfill	0
the	0
need	0
for	0
a	0
more	0
convenient	0
therapy	0
and	0
provide	0
an	0
improved	0
safety	0
/	0
efficacy	0
profile	0
.	0
It	0
has	0
shown	0
promising	0
results	0
alone	0
or	0
in	0
combination	0
with	0
other	0
chemotherapeutic	0
agents	0
in	0
colorectal	3
","	4
breast	4
","	4
pancreaticobiliary	4
","	4
gastric	4
","	4
renal	4
cell	4
and	4
head	4
and	4
neck	4
cancers	4
.	0
The	0
most	0
commonly	0
reported	0
toxic	0
effects	0
of	0
capecitabine	1
are	0
diarrhea	3
","	0
nausea	3
","	0
vomiting	3
","	0
stomatitis	3
and	0
hand	3
-	4
foot	4
syndrome	4
.	0
Capecitabine	1
has	0
a	0
well	0
-	0
established	0
safety	0
profile	0
and	0
can	0
be	0
given	0
safely	0
to	0
patients	0
with	0
advanced	0
age	0
","	0
hepatic	3
and	4
renal	4
dysfunctions	4
.	0
Levodopa	1
-	0
induced	0
dyskinesias	3
in	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
:	0
filling	0
the	0
bench	0
-	0
to	0
-	0
bedside	0
gap	0
.	0
Levodopa	1
is	0
the	0
most	0
effective	0
drug	0
for	0
the	0
treatment	0
of	0
Parkinson	3
'	4
s	4
disease	4
.	0
However	0
","	0
the	0
long	0
-	0
term	0
use	0
of	0
this	0
dopamine	1
precursor	0
is	0
complicated	0
by	0
highly	0
disabling	0
fluctuations	0
and	0
dyskinesias	3
.	0
Although	0
preclinical	0
and	0
clinical	0
findings	0
suggest	0
pulsatile	0
stimulation	0
of	0
striatal	0
postsynaptic	0
receptors	0
as	0
a	0
key	0
mechanism	0
underlying	0
levodopa	1
-	0
induced	0
dyskinesias	3
","	0
their	0
pathogenesis	0
is	0
still	0
unclear	0
.	0
In	0
recent	0
years	0
","	0
evidence	0
from	0
animal	0
models	0
of	0
Parkinson	3
'	4
s	4
disease	4
has	0
provided	0
important	0
information	0
to	0
understand	0
the	0
effect	0
of	0
specific	0
receptor	0
and	0
post	0
-	0
receptor	0
molecular	0
mechanisms	0
underlying	0
the	0
development	0
of	0
dyskinetic	3
movements	4
.	0
Recent	0
preclinical	0
and	0
clinical	0
data	0
from	0
promising	0
lines	0
of	0
research	0
focus	0
on	0
the	0
differential	0
role	0
of	0
presynaptic	0
versus	0
postsynaptic	0
mechanisms	0
","	0
dopamine	1
receptor	0
subtypes	0
","	0
ionotropic	0
and	0
metabotropic	0
glutamate	1
receptors	0
","	0
and	0
non	0
-	0
dopaminergic	0
neurotransmitter	0
systems	0
in	0
the	0
pathophysiology	0
of	0
levodopa	1
-	0
induced	0
dyskinesias	3
.	0
Effects	0
of	0
pallidal	0
neurotensin	1
on	0
haloperidol	1
-	0
induced	0
parkinsonian	3
catalepsy	4
:	0
behavioral	0
and	0
electrophysiological	0
studies	0
.	0
0BJECTIVE	0
:	0
The	0
globus	0
pallidus	0
plays	0
a	0
critical	0
role	0
in	0
movement	0
regulation	0
.	0
Previous	0
studies	0
have	0
indicated	0
that	0
the	0
globus	0
pallidus	0
receives	0
neurotensinergic	0
innervation	0
from	0
the	0
striatum	0
","	0
and	0
systemic	0
administration	0
of	0
a	0
neurotensin	1
analog	0
could	0
produce	0
antiparkinsonian	0
effects	0
.	0
The	0
present	0
study	0
aimed	0
to	0
investigate	0
the	0
effects	0
of	0
pallidal	0
neurotensin	1
on	0
haloperidol	1
-	0
induced	0
parkinsonian	3
symptoms	4
.	0
METH0DS	0
:	0
Behavioral	0
experiments	0
and	0
electrophysiological	0
recordings	0
were	0
performed	0
in	0
the	0
present	0
study	0
.	0
RESULTS	0
:	0
Bilateral	0
infusions	0
of	0
neurotensin	1
into	0
the	0
globus	0
pallidus	0
reversed	0
haloperidol	1
-	0
induced	0
parkinsonian	3
catalepsy	4
in	0
rats	0
.	0
Electrophysiological	0
recordings	0
showed	0
that	0
microinjection	0
of	0
neurotensin	1
induced	0
excitation	0
of	0
pallidal	0
neurons	0
in	0
the	0
presence	0
of	0
systemic	0
haloperidol	1
administration	0
.	0
The	0
neurotensin	1
type	2
-	2
1	2
receptor	2
antagonist	2
SR48692	1
blocked	0
both	0
the	0
behavioral	0
and	0
the	0
electrophysiological	0
effects	0
induced	0
by	0
neurotensin	1
.	0
C0NCLUSI0N	0
:	0
Activation	0
of	0
pallidal	0
neurotensin	1
receptors	0
may	0
be	0
involved	0
in	0
neurotensin	1
-	0
induced	0
antiparkinsonian	0
effects	0
.	0
Carmofur	1
-	0
induced	0
organic	3
mental	4
disorders	4
.	0
0rganic	3
mental	4
disorder	4
was	0
observed	0
in	0
a	0
29	0
-	0
year	0
-	0
old	0
female	0
in	0
the	0
prognostic	0
period	0
after	0
the	0
onset	0
of	0
carmofur	1
-	0
induced	0
leukoencephalopathy	3
.	0
Symptoms	0
such	0
as	0
euphoria	0
","	0
emotional	0
lability	0
and	0
puerile	0
attitude	0
noted	0
in	0
the	0
patient	0
were	0
diagnosed	0
as	0
organic	3
personality	4
syndrome	4
according	0
to	0
the	0
criteria	0
defined	0
in	0
the	0
DSM	0
-	0
III	0
-	0
R	0
.	0
It	0
is	0
referred	0
to	0
as	0
a	0
frontal	3
lobe	4
syndrome	4
.	0
Brain	0
CT	0
revealed	0
a	0
periventricular	0
low	0
density	0
area	0
in	0
the	0
frontal	0
white	0
matter	0
and	0
moderate	0
dilatation	0
of	0
the	0
lateral	0
ventricles	0
especially	0
at	0
the	0
bilateral	0
anterior	0
horns	0
.	0
Consequently	0
","	0
carmofur	1
-	0
induced	0
leukoencephalopathy	3
may	0
uncommonly	0
result	0
in	0
organic	3
personality	4
syndrome	4
in	0
the	0
residual	0
state	0
.	0
It	0
may	0
be	0
attributed	0
to	0
the	0
structural	3
damage	4
to	4
the	4
frontal	4
lobe	4
.	0
Butyrylcholinesterase	0
gene	0
mutations	0
in	0
patients	0
with	0
prolonged	0
apnea	3
after	0
succinylcholine	1
for	0
electroconvulsive	0
therapy	0
.	0
BACKGR0UND	0
:	0
patients	0
undergoing	0
electroconvulsive	0
therapy	0
(	0
ECT	0
)	0
often	0
receive	0
succinylcholine	1
as	0
part	0
of	0
the	0
anesthetic	0
procedure	0
.	0
The	0
duration	0
of	0
action	0
may	0
be	0
prolonged	0
in	0
patients	0
with	0
genetic	0
variants	0
of	0
the	0
butyrylcholinesterase	0
enzyme	0
(	0
BChE	0
)	0
","	0
the	0
most	0
common	0
being	0
the	0
K	0
-	0
and	0
the	0
A	0
-	0
variants	0
.	0
The	0
aim	0
of	0
the	0
study	0
was	0
to	0
assess	0
the	0
clinical	0
significance	0
of	0
genetic	0
variants	0
in	0
butyrylcholinesterase	0
gene	0
(	0
BCHE	0
)	0
in	0
patients	0
with	0
a	0
suspected	0
prolonged	0
duration	0
of	0
action	0
of	0
succinylcholine	1
after	0
ECT	0
.	0
METH0DS	0
:	0
a	0
total	0
of	0
13	0
patients	0
were	0
referred	0
to	0
the	0
Danish	0
Cholinesterase	0
Research	0
Unit	0
after	0
ECT	0
during	0
38	0
months	0
.	0
We	0
determined	0
the	0
BChE	0
activity	0
and	0
the	0
BCHE	0
genotype	0
using	0
molecular	0
genetic	0
methods	0
","	0
the	0
duration	0
of	0
apnea	3
","	0
time	0
to	0
sufficient	0
spontaneous	0
ventilation	0
and	0
whether	0
neuromuscular	0
monitoring	0
was	0
used	0
.	0
The	0
duration	0
of	0
apnea	3
was	0
compared	0
with	0
published	0
data	0
on	0
normal	0
subjects	0
.	0
RESULTS	0
:	0
in	0
11	0
patients	0
","	0
mutations	0
were	0
found	0
in	0
the	0
BCHE	0
gene	0
","	0
the	0
K	0
-	0
variant	0
being	0
the	0
most	0
frequent	0
.	0
The	0
duration	0
of	0
apnea	3
was	0
5	0
-	0
15	0
min	0
compared	0
with	0
3	0
-	0
5	0
.	0
3	0
min	0
from	0
the	0
literature	0
.	0
Severe	0
distress	0
was	0
noted	0
in	0
the	0
recovery	0
phase	0
in	0
two	0
patients	0
.	0
Neuromuscular	0
monitoring	0
was	0
used	0
in	0
two	0
patients	0
.	0
C0NCLUSI0N	0
:	0
eleven	0
of	0
13	0
patients	0
with	0
a	0
prolonged	0
duration	0
of	0
action	0
of	0
succinylcholine	1
had	0
mutations	0
in	0
BCHE	0
","	0
indicating	0
that	0
this	0
is	0
the	0
possible	0
reason	0
for	0
a	0
prolonged	0
period	0
of	0
apnea	3
.	0
We	0
recommend	0
objective	0
neuromuscular	0
monitoring	0
during	0
the	0
first	0
ECT	0
.	0
Perhexiline	1
maleate	2
and	0
peripheral	3
neuropathy	4
.	0
Peripheral	3
neuropathy	4
has	0
been	0
noted	0
as	0
a	0
complication	0
of	0
therapy	0
with	0
perhexiline	1
maleate	2
","	0
a	0
drug	0
widely	0
used	0
in	0
France	0
(	0
and	0
in	0
clinical	0
trials	0
in	0
the	0
United	0
States	0
)	0
for	0
the	0
prophylactic	0
treatment	0
of	0
angina	3
pectoris	4
.	0
In	0
24	0
patients	0
with	0
this	0
complication	0
","	0
the	0
marked	0
slowing	0
of	0
motor	0
nerve	0
conduction	0
velocity	0
and	0
the	0
electromyographic	0
changes	0
imply	0
mainly	0
a	0
demyelinating	3
disorder	4
.	0
Improvement	0
was	0
noted	0
with	0
cessation	0
of	0
therapy	0
.	0
In	0
a	0
few	0
cases	0
the	0
presence	0
of	0
active	0
denervation	0
signified	0
a	0
poor	0
prognosis	0
","	0
with	0
only	0
slight	0
improvement	0
.	0
The	0
underlying	0
mechanism	0
causing	0
the	0
neuropathy	3
is	0
not	0
yet	0
fully	0
known	0
","	0
although	0
some	0
evidence	0
indicates	0
that	0
it	0
may	0
be	0
a	0
lipid	0
storage	0
process	0
.	0
A	0
phase	0
I	0
study	0
of	0
4	1
'	2
-	2
0	2
-	2
tetrahydropyranyladriamycin	2
.	0
Clinical	0
pharmacology	0
and	0
pharmacokinetics	0
.	0
A	0
Phase	0
I	0
study	0
of	0
intravenous	0
(	0
IV	0
)	0
bolus	0
4	1
'	2
-	2
0	2
-	2
tetrahydropyranyladriamycin	2
(	0
Pirarubicin	1
)	0
was	0
done	0
in	0
55	0
patients	0
in	0
good	0
performance	0
status	0
with	0
refractory	0
tumors	3
.	0
Twenty	0
-	0
six	0
had	0
minimal	0
prior	0
therapy	0
(	0
good	0
risk	0
)	0
","	0
23	0
had	0
extensive	0
prior	0
therapy	0
(	0
poor	0
risk	0
)	0
","	0
and	0
six	0
had	0
renal	3
and	4
/	4
or	4
hepatic	4
dysfunction	4
.	0
A	0
total	0
of	0
167	0
courses	0
at	0
doses	0
of	0
15	0
to	0
70	0
mg	0
/	0
m2	0
were	0
evaluable	0
.	0
Maximum	0
tolerated	0
dose	0
in	0
good	0
-	0
risk	0
patients	0
was	0
70	0
mg	0
/	0
m2	0
","	0
and	0
in	0
poor	0
-	0
risk	0
patients	0
","	0
60	0
mg	0
/	0
m2	0
.	0
The	0
dose	0
-	0
limiting	0
toxic	0
effect	0
was	0
transient	0
noncumulative	0
granulocytopenia	3
.	0
Granulocyte	0
nadir	0
was	0
on	0
day	0
14	0
(	0
range	0
","	0
4	0
-	0
22	0
)	0
.	0
Less	0
frequent	0
toxic	0
effects	0
included	0
thrombocytopenia	3
","	0
anemia	3
","	0
nausea	3
","	0
mild	0
alopecia	3
","	0
phlebitis	3
","	0
and	0
mucositis	3
.	0
Myelosuppression	3
was	0
more	0
in	0
patients	0
with	0
hepatic	3
dysfunction	4
.	0
Pharmacokinetic	0
analyses	0
in	0
21	0
patients	0
revealed	0
Pirarubicin	1
plasma	0
T	0
1	0
/	0
2	0
alpha	0
(	0
+	0
/	0
-	0
SE	0
)	0
of	0
2	0
.	0
5	0
+	0
/	0
-	0
0	0
.	0
85	0
minutes	0
","	0
T	0
beta	0
1	0
/	0
2	0
of	0
25	0
.	0
6	0
+	0
/	0
-	0
6	0
.	0
5	0
minutes	0
","	0
and	0
T	0
1	0
/	0
2	0
gamma	0
of	0
23	0
.	0
6	0
+	0
/	0
-	0
7	0
.	0
6	0
hours	0
.	0
The	0
area	0
under	0
the	0
curve	0
was	0
537	0
+	0
/	0
-	0
149	0
ng	0
/	0
ml	0
x	0
hours	0
","	0
volume	0
of	0
distribution	0
(	0
Vd	0
)	0
3504	0
+	0
/	0
-	0
644	0
l	0
/	0
m2	0
","	0
and	0
total	0
clearance	0
(	0
ClT	0
)	0
was	0
204	0
+	0
39	0
.	0
3	0
l	0
/	0
hour	0
/	0
m2	0
.	0
Adriamycinol	1
","	0
doxorubicin	1
","	0
adriamycinone	1
","	0
and	0
tetrahydropyranyladriamycinol	1
were	0
the	0
metabolites	0
detected	0
in	0
plasma	0
and	0
the	0
amount	0
of	0
doxorubicin	1
was	0
less	0
than	0
or	0
equal	0
to	0
10	0
%	0
of	0
the	0
total	0
metabolites	0
.	0
Urinary	0
excretion	0
of	0
Pirarubicin	1
in	0
the	0
first	0
24	0
hours	0
was	0
less	0
than	0
or	0
equal	0
to	0
10	0
%	0
.	0
Activity	0
was	0
noted	0
in	0
mesothelioma	3
","	0
leiomyosarcoma	3
","	0
and	0
basal	3
cell	4
carcinoma	4
.	0
The	0
recommended	0
starting	0
dose	0
for	0
Phase	0
II	0
trials	0
is	0
60	0
mg	0
/	0
m2	0
IV	0
bolus	0
every	0
3	0
weeks	0
.	0
0cular	3
and	4
auditory	4
toxicity	4
in	0
hemodialyzed	0
patients	0
receiving	0
desferrioxamine	1
.	0
During	0
an	0
18	0
-	0
month	0
period	0
of	0
study	0
41	0
hemodialyzed	0
patients	0
receiving	0
desferrioxamine	1
(	0
10	0
-	0
40	0
mg	0
/	0
kg	0
BW	0
/	0
3	0
times	0
weekly	0
)	0
for	0
the	0
first	0
time	0
were	0
monitored	0
for	0
detection	0
of	0
audiovisual	3
toxicity	4
.	0
6	0
patients	0
presented	0
clinical	0
symptoms	0
of	0
visual	3
or	4
auditory	4
toxicity	4
.	0
Moreover	0
","	0
detailed	0
ophthalmologic	0
and	0
audiologic	0
studies	0
disclosed	0
abnormalities	0
in	0
7	0
more	0
asymptomatic	0
patients	0
.	0
Visual	3
toxicity	4
was	0
of	0
retinal	0
origin	0
and	0
was	0
characterized	0
by	0
a	0
tritan	0
-	0
type	0
dyschromatopsy	3
","	0
sometimes	0
associated	0
with	0
a	3
loss	4
of	4
visual	4
acuity	4
and	0
pigmentary	3
retinal	4
deposits	4
.	0
Auditory	3
toxicity	4
was	0
characterized	0
by	0
a	0
mid	0
-	0
to	0
high	0
-	0
frequency	0
neurosensorial	3
hearing	4
loss	4
and	0
the	0
lesion	0
was	0
of	0
the	0
cochlear	0
type	0
.	0
Desferrioxamine	1
withdrawal	0
resulted	0
in	0
a	0
complete	0
recovery	0
of	0
visual	0
function	0
in	0
1	0
patient	0
and	0
partial	0
recovery	0
in	0
3	0
","	0
and	0
a	0
complete	0
reversal	0
of	0
hearing	3
loss	4
in	0
3	0
patients	0
and	0
partial	0
recovery	0
in	0
3	0
.	0
This	0
toxicity	3
appeared	0
in	0
patients	0
receiving	0
the	0
higher	0
doses	0
of	0
desferrioxamine	1
or	0
coincided	0
with	0
the	0
normalization	0
of	0
ferritin	0
or	0
aluminium	1
serum	0
levels	0
.	0
The	0
data	0
indicate	0
that	0
audiovisual	3
toxicity	4
is	0
not	0
an	0
infrequent	0
complication	0
in	0
hemodialyzed	0
patients	0
receiving	0
desferrioxamine	1
.	0
Periodical	0
audiovisual	0
monitoring	0
should	0
be	0
performed	0
on	0
hemodialyzed	0
patients	0
receiving	0
the	0
drug	0
in	0
order	0
to	0
detect	0
adverse	0
effects	0
as	0
early	0
as	0
possible	0
.	0
Serial	0
epilepsy	3
caused	0
by	0
levodopa	1
/	2
carbidopa	2
administration	0
in	0
two	0
patients	0
on	0
hemodialysis	0
.	0
Two	0
patients	0
with	0
similar	0
clinical	0
features	0
are	0
presented	0
:	0
both	0
patients	0
had	0
chronic	3
renal	4
failure	4
","	0
on	0
hemodialysis	0
for	0
many	0
years	0
but	0
recently	0
begun	0
on	0
a	0
high	0
-	0
flux	0
dialyzer	0
;	0
both	0
had	0
been	0
receiving	0
a	0
carbidopa	1
/	2
levodopa	2
preparation	0
;	0
and	0
both	0
had	0
the	0
onset	0
of	0
hallucinosis	3
and	0
recurrent	0
seizures	3
","	0
which	0
were	0
refractory	0
to	0
anticonvulsants	0
.	0
The	0
first	0
patient	0
died	0
without	0
a	0
diagnosis	0
;	0
the	0
second	0
patient	0
had	0
a	0
dramatic	0
recovery	0
following	0
the	0
administration	0
of	0
vitamin	1
B6	2
.	0
Neither	0
patient	0
was	0
considered	0
to	0
have	0
a	0
renal	0
state	0
sufficiently	0
severe	0
enough	0
to	0
explain	0
their	0
presentation	0
.	0
Randomized	0
","	0
double	0
-	0
blind	0
trial	0
of	0
mazindol	1
in	0
Duchenne	3
dystrophy	4
.	0
There	0
is	0
evidence	0
that	0
growth	0
hormone	0
may	0
be	0
related	0
to	0
the	0
progression	0
of	0
weakness	3
in	0
Duchenne	3
dystrophy	4
.	0
We	0
conducted	0
a	0
12	0
-	0
month	0
controlled	0
trial	0
of	0
mazindol	1
","	0
a	0
putative	0
growth	0
hormone	0
secretion	0
inhibitor	0
","	0
in	0
83	0
boys	0
with	0
Duchenne	3
dystrophy	4
.	0
Muscle	0
strength	0
","	0
contractures	0
","	0
functional	0
ability	0
and	0
pulmonary	0
function	0
were	0
tested	0
at	0
baseline	0
","	0
and	0
6	0
and	0
12	0
months	0
after	0
treatment	0
with	0
mazindol	1
(	0
3	0
mg	0
/	0
d	0
)	0
or	0
placebo	0
.	0
The	0
study	0
was	0
designed	0
to	0
have	0
a	0
power	0
of	0
greater	0
than	0
0	0
.	0
90	0
to	0
detect	0
a	0
slowing	0
to	0
25	0
%	0
of	0
the	0
expected	0
rate	0
of	0
progression	0
of	0
weakness	3
at	0
P	0
less	0
than	0
0	0
.	0
5	0
.	0
Mazindol	1
did	0
not	0
benefit	0
strength	0
at	0
any	0
point	0
in	0
the	0
study	0
.	0
Side	0
effects	0
attributable	0
to	0
mazindol	1
included	0
decreased	3
appetite	4
(	0
36	0
%	0
)	0
","	0
dry	3
mouth	4
(	0
10	0
%	0
)	0
","	0
behavioral	0
change	0
(	0
22	0
%	0
)	0
","	0
and	0
gastrointestinal	3
symptoms	4
(	0
18	0
%	0
)	0
;	0
mazindol	1
dosage	0
was	0
reduced	0
in	0
43	0
%	0
of	0
patients	0
.	0
The	0
effect	0
of	0
mazindol	1
on	0
GH	0
secretion	0
was	0
estimated	0
indirectly	0
by	0
comparing	0
the	0
postabsorptive	0
IGF	0
-	0
I	0
levels	0
obtained	0
following	0
3	0
","	0
6	0
","	0
9	0
","	0
and	0
12	0
months	0
in	0
the	0
mazindol	1
treated	0
to	0
those	0
in	0
the	0
placebo	0
groups	0
.	0
Although	0
mazindol	1
-	0
treated	0
patients	0
gained	0
less	0
weight	0
and	0
height	0
than	0
placebo	0
-	0
treated	0
patients	0
","	0
no	0
significant	0
effect	0
on	0
IGF	0
-	0
I	0
levels	0
was	0
observed	0
.	0
Mazindol	1
doses	0
not	0
slow	0
the	0
progression	0
of	0
weakness	3
in	0
Duchenne	3
dystrophy	4
.	0
Facilitation	0
of	0
memory	0
retrieval	0
by	0
pre	0
-	0
test	0
morphine	1
and	0
its	0
state	0
dependency	0
in	0
the	0
step	0
-	0
through	0
type	0
passive	0
avoidance	0
learning	0
test	0
in	0
mice	0
.	0
Amnesia	3
produced	0
by	0
scopolamine	1
and	0
cycloheximide	1
were	0
reversed	0
by	0
morphine	1
given	0
30	0
min	0
before	0
the	0
test	0
trial	0
(	0
pre	0
-	0
test	0
)	0
","	0
and	0
pre	0
-	0
test	0
morphine	1
also	0
facilitated	0
the	0
memory	0
retrieval	0
in	0
the	0
animals	0
administered	0
naloxone	1
during	0
the	0
training	0
trial	0
.	0
Similarly	0
","	0
pre	0
-	0
test	0
scopolamine	1
partially	0
reversed	0
the	0
scopolamine	1
-	0
induced	0
amnesia	3
","	0
but	0
not	0
significantly	0
;	0
and	0
pre	0
-	0
test	0
cycloheximide	1
failed	0
to	0
reverse	0
the	0
cycloheximide	1
-	0
induced	0
amnesia	3
.	0
These	0
results	0
suggest	0
that	0
the	0
facilitation	0
of	0
memory	0
retrieval	0
by	0
pre	0
-	0
test	0
morphine	1
might	0
be	0
the	0
direct	0
action	0
of	0
morphine	1
rather	0
than	0
a	0
state	0
dependent	0
effect	0
.	0
Naloxone	1
reverses	0
the	0
antihypertensive	0
effect	0
of	0
clonidine	1
.	0
In	0
unanesthetized	0
","	0
spontaneously	0
hypertensive	3
rats	0
the	0
decrease	0
in	0
blood	0
pressure	0
and	0
heart	0
rate	0
produced	0
by	0
intravenous	0
clonidine	1
","	0
5	0
to	0
20	0
micrograms	0
/	0
kg	0
","	0
was	0
inhibited	0
or	0
reversed	0
by	0
nalozone	1
","	0
0	0
.	0
2	0
to	0
2	0
mg	0
/	0
kg	0
.	0
The	0
hypotensive	3
effect	0
of	0
100	0
mg	0
/	0
kg	0
alpha	1
-	2
methyldopa	2
was	0
also	0
partially	0
reversed	0
by	0
naloxone	1
.	0
Naloxone	1
alone	0
did	0
not	0
affect	0
either	0
blood	0
pressure	0
or	0
heart	0
rate	0
.	0
In	0
brain	0
membranes	0
from	0
spontaneously	0
hypertensive	3
rats	0
clonidine	1
","	0
10	0
(	0
-	0
8	0
)	0
to	0
10	0
(	0
-	0
5	0
)	0
M	0
","	0
did	0
not	0
influence	0
stereoselective	0
binding	0
of	0
[	1
3H	2
]	2
-	2
naloxone	2
(	0
8	0
nM	0
)	0
","	0
and	0
naloxone	1
","	0
10	0
(	0
-	0
8	0
)	0
to	0
10	0
(	0
-	0
4	0
)	0
M	0
","	0
did	0
not	0
influence	0
clonidine	1
-	0
suppressible	0
binding	0
of	0
[	1
3H	2
]	2
-	2
dihydroergocryptine	2
(	0
1	0
nM	0
)	0
.	0
These	0
findings	0
indicate	0
that	0
in	0
spontaneously	0
hypertensive	3
rats	0
the	0
effects	0
of	0
central	0
alpha	0
-	0
adrenoceptor	0
stimulation	0
involve	0
activation	0
of	0
opiate	0
receptors	0
.	0
As	0
naloxone	1
and	0
clonidine	1
do	0
not	0
appear	0
to	0
interact	0
with	0
the	0
same	0
receptor	0
site	0
","	0
the	0
observed	0
functional	0
antagonism	0
suggests	0
the	0
release	0
of	0
an	0
endogenous	0
opiate	0
by	0
clonidine	1
or	0
alpha	1
-	2
methyldopa	2
and	0
the	0
possible	0
role	0
of	0
the	0
opiate	0
in	0
the	0
central	0
control	0
of	0
sympathetic	0
tone	0
.	0
Neurotoxicity	3
of	0
halogenated	1
hydroxyquinolines	2
:	0
clinical	0
analysis	0
of	0
cases	0
reported	0
outside	0
Japan	0
.	0
An	0
analysis	0
is	0
presented	0
of	0
220	0
cases	0
of	0
possible	0
neurotoxic	3
reactions	0
to	0
halogenated	1
hydroxyquinolines	2
reported	0
from	0
outside	0
Japan	0
.	0
In	0
80	0
cases	0
insufficient	0
information	0
was	0
available	0
for	0
adequate	0
comment	0
and	0
in	0
29	0
a	0
relationship	0
to	0
the	0
administration	0
of	0
clioquinol	1
could	0
be	0
excluded	0
.	0
0f	0
the	0
remainder	0
","	0
a	0
relationship	0
to	0
clioquinol	1
was	0
considered	0
probable	0
in	0
42	0
and	0
possible	0
in	0
69	0
cases	0
.	0
In	0
six	0
of	0
the	0
probable	0
cases	0
the	0
neurological	3
disturbance	4
consisted	0
of	0
an	0
acute	0
reversible	0
encephalopathy	3
usually	0
related	0
to	0
the	0
ingestion	0
of	0
a	0
high	0
dose	0
of	0
clioquinol	1
over	0
a	0
short	0
period	0
.	0
The	0
most	0
common	0
manifestation	0
","	0
observed	0
in	0
15	0
further	0
cases	0
","	0
was	0
isolated	0
optic	3
atrophy	4
.	0
This	0
was	0
most	0
frequently	0
found	0
in	0
children	0
","	0
many	0
of	0
whom	0
had	0
received	0
clioquinol	1
as	0
treatment	0
for	0
acrodermatitis	3
enteropathica	4
.	0
In	0
the	0
remaining	0
cases	0
","	0
a	0
combination	0
of	0
myelopathy	3
","	0
visual	3
disturbance	4
","	0
and	0
peripheral	3
neuropathy	4
was	0
the	0
most	0
common	0
manifestation	0
.	0
Isolated	0
myelopathy	3
or	0
peripheral	3
neuropathy	4
","	0
or	0
these	0
manifestations	0
occurring	0
together	0
","	0
were	0
infrequent	0
.	0
The	0
onset	0
of	0
all	0
manifestations	0
(	0
except	0
toxic	0
encephalopathy	3
)	0
was	0
usually	0
subacute	0
","	0
with	0
subsequent	0
partial	0
recovery	0
.	0
0lder	0
subjects	0
tended	0
to	0
display	0
more	0
side	0
effects	0
.	0
The	0
full	0
syndrome	0
of	0
subacute	0
myelo	3
-	4
optic	4
neuropathy	4
was	0
more	0
frequent	0
in	0
women	0
","	0
but	0
they	0
tended	0
to	0
have	0
taken	0
greater	0
quantities	0
of	0
the	0
drug	0
.	0
Prazosin	1
-	0
induced	0
stress	3
incontinence	4
.	0
A	0
case	0
of	0
genuine	0
stress	3
incontinence	4
due	0
to	0
prazosin	1
","	0
a	0
common	0
antihypertensive	0
drug	0
","	0
is	0
presented	0
.	0
Prazosin	1
exerts	0
its	0
antihypertensive	0
effects	0
through	0
vasodilatation	0
caused	0
by	0
selective	0
blockade	0
of	0
postsynaptic	0
alpha	0
-	0
1	0
adrenergic	0
receptors	0
.	0
As	0
an	0
alpha	0
-	0
blocker	0
","	0
it	0
also	0
exerts	0
a	0
significant	0
relaxant	0
effect	0
on	0
the	0
bladder	0
neck	0
and	0
urethra	0
.	0
The	0
patient	0
'	0
s	0
clinical	0
course	0
is	0
described	0
and	0
correlated	0
with	0
initial	0
urodynamic	0
studies	0
while	0
on	0
prazosin	1
and	0
subsequent	0
studies	0
while	0
taking	0
verapamil	1
.	0
Her	0
incontinence	3
resolved	0
with	0
the	0
change	0
of	0
medication	0
.	0
The	0
restoration	0
of	0
continence	0
was	0
accompanied	0
by	0
a	0
substantial	0
rise	0
in	0
maximum	0
urethral	0
pressure	0
","	0
maximum	0
urethral	0
closure	0
pressure	0
","	0
and	0
functional	0
urethral	0
length	0
.	0
Patients	0
who	0
present	0
with	0
stress	3
incontinence	4
while	0
taking	0
prazosin	1
should	0
change	0
their	0
antihypertensive	0
medication	0
before	0
considering	0
surgery	0
","	0
because	0
their	0
incontinence	3
may	0
resolve	0
spontaneously	0
with	0
a	0
change	0
in	0
drug	0
therapy	0
.	0
Myocardial	3
infarction	4
following	0
sublingual	0
administration	0
of	0
isosorbide	1
dinitrate	2
.	0
A	0
78	0
-	0
year	0
-	0
old	0
with	0
healed	0
septal	0
necrosis	3
suffered	0
a	0
recurrent	0
myocardial	3
infarction	4
of	0
the	0
anterior	0
wall	0
following	0
the	0
administration	0
of	0
isosorbide	1
dinitrate	2
5	0
mg	0
sublingually	0
.	0
After	0
detailing	0
the	0
course	0
of	0
events	0
","	0
we	0
discuss	0
the	0
role	0
of	0
paradoxical	0
coronary	0
spasm	3
and	0
hypotension	3
-	0
mediated	0
myocardial	3
ischemia	4
occurring	0
downstream	0
to	0
significant	0
coronary	3
arterial	4
stenosis	4
in	0
the	0
pathophysiology	0
of	0
acute	3
coronary	4
insufficiency	4
.	0
Comparison	0
of	0
the	0
respiratory	0
effects	0
of	0
i	0
.	0
v	0
.	0
infusions	0
of	0
morphine	1
and	0
regional	0
analgesia	0
by	0
extradural	0
block	0
.	0
The	0
incidence	0
of	0
postoperative	0
respiratory	0
apnoea	3
was	0
compared	0
between	0
five	0
patients	0
receiving	0
a	0
continuous	0
i	0
.	0
v	0
.	0
infusion	0
of	0
morphine	1
(	0
mean	0
73	0
.	0
6	0
mg	0
)	0
and	0
five	0
patients	0
receiving	0
a	0
continuous	0
extradural	0
infusion	0
of	0
0	0
.	0
25	0
%	0
bupivacaine	1
(	0
mean	0
192	0
mg	0
)	0
in	0
the	0
24	0
-	0
h	0
period	0
following	0
upper	0
abdominal	0
surgery	0
.	0
Monitoring	0
consisted	0
of	0
airflow	0
detection	0
by	0
a	0
carbon	1
dioxide	2
analyser	0
","	0
chest	0
wall	0
movement	0
detected	0
by	0
pneumatic	0
capsules	0
","	0
and	0
continuous	0
electrocardiograph	0
recorded	0
with	0
a	0
Holter	0
ambulatory	0
monitor	0
.	0
Both	0
obstructive	3
(	4
P	4
less	4
than	4
0	4
.	4
5	4
)	4
and	4
central	4
apnoea	4
(	0
P	0
less	0
than	0
0	0
.	0
5	0
)	0
occurred	0
more	0
frequently	0
in	0
patients	0
who	0
had	0
a	0
morphine	1
infusion	0
.	0
There	0
was	0
also	0
a	0
higher	0
incidence	0
of	0
tachyarrhythmias	3
(	0
P	0
less	0
than	0
0	0
.	0
5	0
)	0
and	0
ventricular	3
ectopic	4
beats	4
(	0
P	0
less	0
than	0
0	0
.	0
5	0
)	0
in	0
the	0
morphine	1
infusion	0
group	0
.	0
Effects	0
of	0
aminophylline	1
on	0
the	0
threshold	0
for	0
initiating	0
ventricular	3
fibrillation	4
during	0
respiratory	3
failure	4
.	0
Cardiac	3
arrhythmias	4
have	0
frequently	0
been	0
reported	0
in	0
association	0
with	0
respiratory	3
failure	4
.	0
The	0
possible	0
additive	0
role	0
of	0
pharmacologic	0
agents	0
in	0
precipitating	0
cardiac	3
disturbances	4
in	0
patients	0
with	0
respiratory	3
failure	4
has	0
only	0
recently	0
been	0
emphasized	0
.	0
The	0
effects	0
of	0
aminophylline	1
on	0
the	0
ventricular	3
fibrillation	4
threshold	0
during	0
normal	0
acid	0
-	0
base	0
conditions	0
and	0
during	0
respiratory	3
failure	4
were	0
studied	0
in	0
anesthetized	0
open	0
chest	0
dogs	0
.	0
The	0
ventricular	3
fibrillation	4
threshold	0
was	0
measured	0
by	0
passing	0
a	0
gated	0
train	0
of	0
12	0
constant	0
current	0
pulses	0
through	0
the	0
ventricular	0
myocardium	0
during	0
the	0
vulnerable	0
period	0
of	0
the	0
cardiac	0
cycle	0
.	0
During	0
the	0
infusion	0
of	0
aminophylline	1
","	0
the	0
ventricular	3
fibrillation	4
threshold	0
was	0
reduced	0
by	0
30	0
to	0
40	0
percent	0
of	0
the	0
control	0
when	0
pH	0
and	0
partial	0
pressures	0
of	0
oxygen	1
(	0
P02	1
)	0
and	0
carbon	1
dioxide	2
(	0
C02	1
)	0
were	0
kept	0
within	0
normal	0
limits	0
.	0
When	0
respiratory	3
failure	4
was	0
produced	0
by	0
hypoventilation	3
(	0
pH	0
7	0
.	0
5	0
to	0
7	0
.	0
25	0
;	0
PC02	0
70	0
to	0
100	0
mm	0
Hg	0
:	0
P02	0
20	0
to	0
40	0
mm	0
Hg	0
)	0
","	0
infusion	0
of	0
aminophylline	1
resulted	0
in	0
an	0
even	0
greater	0
decrease	0
in	0
ventricular	3
fibrillation	4
threshold	0
to	0
60	0
percent	0
of	0
the	0
control	0
level	0
.	0
These	0
experiments	0
suggest	0
that	0
although	0
many	0
factors	0
may	0
contribute	0
to	0
the	0
increased	0
incidence	0
of	0
ventricular	3
arrhythmias	4
in	0
respiratory	3
failure	4
","	0
pharmacologic	0
agents	0
","	0
particularly	0
aminophylline	1
","	0
may	0
play	0
a	0
significant	0
role	0
.	0
Pentoxifylline	1
(	0
Trental	1
)	0
does	0
not	0
inhibit	0
dipyridamole	1
-	0
induced	0
coronary	0
hyperemia	3
:	0
implications	0
for	0
dipyridamole	1
-	0
thallium	1
-	0
201	0
myocardial	0
imaging	0
.	0
Dipyridamole	1
-	0
thallium	1
-	0
201	0
imaging	0
is	0
often	0
performed	0
in	0
patients	0
unable	0
to	0
exercise	0
because	0
of	0
peripheral	3
vascular	4
disease	4
.	0
Many	0
of	0
these	0
patients	0
are	0
taking	0
pentoxifylline	1
(	0
Trental	1
)	0
","	0
a	0
methylxanthine	1
derivative	0
which	0
may	0
improve	0
intermittent	3
claudication	4
.	0
Whether	0
pentoxifylline	1
inhibits	0
dipyridamole	1
-	0
induced	0
coronary	0
hyperemia	3
like	0
other	0
methylxanthines	1
such	0
as	0
theophylline	1
and	0
should	0
be	0
stopped	0
prior	0
to	0
dipyridamole	1
-	0
thallium	1
-	0
201	0
imaging	0
is	0
unknown	0
.	0
Therefore	0
","	0
we	0
studied	0
the	0
hyperemic	0
response	0
to	0
dipyridamole	1
in	0
seven	0
open	0
-	0
chest	0
anesthetized	0
dogs	0
after	0
pretreatment	0
with	0
either	0
pentoxifylline	1
(	0
0	0
","	0
7	0
.	0
5	0
","	0
or	0
15	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
or	0
theophylline	1
(	0
3	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
.	0
Baseline	0
circumflex	0
coronary	0
blood	0
flows	0
did	0
not	0
differ	0
significantly	0
among	0
treatment	0
groups	0
.	0
Dipyridamole	1
significantly	0
increased	0
coronary	0
blood	0
flow	0
before	0
and	0
after	0
7	0
.	0
5	0
or	0
15	0
mm	0
/	0
kg	0
i	0
.	0
v	0
.	0
pentoxifylline	1
(	0
p	0
less	0
than	0
0	0
.	0
2	0
)	0
.	0
Neither	0
dose	0
of	0
pentoxifylline	1
significantly	0
decreased	0
the	0
dipyridamole	1
-	0
induced	0
hyperemia	3
","	0
while	0
peak	0
coronary	0
blood	0
flow	0
was	0
significantly	0
lower	0
after	0
theophylline	1
(	0
p	0
less	0
than	0
0	0
.	0
1	0
)	0
.	0
We	0
conclude	0
that	0
pentoxyifylline	1
does	0
not	0
inhibit	0
dipyridamole	1
-	0
induced	0
coronary	0
hyperemia	3
even	0
at	0
high	0
doses	0
.	0
Cause	0
of	0
death	3
among	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
:	0
a	0
rare	0
mortality	0
due	0
to	0
cerebral	3
haemorrhage	4
.	0
Causes	0
of	0
death	3
","	0
with	0
special	0
reference	0
to	0
cerebral	3
haemorrhage	4
","	0
among	0
240	0
patients	0
with	0
pathologically	0
verified	0
Parkinson	3
'	4
s	4
disease	4
were	0
investigated	0
using	0
the	0
Annuals	0
of	0
the	0
Pathological	0
Autopsy	0
Cases	0
in	0
Japan	0
from	0
1981	0
to	0
1985	0
.	0
The	0
leading	0
causes	0
of	0
death	3
were	0
pneumonia	3
and	0
bronchitis	3
(	0
44	0
.	0
1	0
%	0
)	0
","	0
malignant	0
neoplasms	3
(	0
11	0
.	0
6	0
%	0
)	0
","	0
heart	3
diseases	4
(	0
4	0
.	0
1	0
%	0
)	0
","	0
cerebral	3
infarction	4
(	0
3	0
.	0
7	0
%	0
)	0
and	0
septicaemia	3
(	0
3	0
.	0
3	0
%	0
)	0
.	0
Cerebral	3
haemorrhage	4
was	0
the	0
11th	0
most	0
frequent	0
cause	0
of	0
death	3
","	0
accounting	0
for	0
only	0
0	0
.	0
8	0
%	0
of	0
deaths	3
among	0
the	0
patients	0
","	0
whereas	0
it	0
was	0
the	0
5th	0
most	0
common	0
cause	0
of	0
death	3
among	0
the	0
Japanese	0
general	0
population	0
in	0
1985	0
.	0
The	0
low	0
incidence	0
of	0
cerebral	3
haemorrhage	4
as	0
a	0
cause	0
of	0
death	3
in	0
patients	0
with	0
Parkinson	3
'	4
s	4
disease	4
may	0
reflect	0
the	0
hypotensive	3
effect	0
of	0
levodopa	1
and	0
a	0
hypotensive	3
mechanism	0
due	0
to	0
reduced	0
noradrenaline	1
levels	0
in	0
the	0
parkinsonian	3
brain	0
.	0
Possible	0
intramuscular	0
midazolam	1
-	0
associated	0
cardiorespiratory	3
arrest	4
and	0
death	3
.	0
Midazolam	1
hydrochloride	2
is	0
commonly	0
used	0
for	0
dental	0
or	0
endoscopic	0
procedures	0
.	0
Although	0
generally	0
consisted	0
safe	0
when	0
given	0
intramuscularly	0
","	0
intravenous	0
administration	0
is	0
known	0
to	0
cause	0
respiratory	3
and	4
cardiovascular	4
depression	4
.	0
This	0
report	0
describes	0
the	0
first	0
published	0
case	0
of	0
cardiorespiratory	3
arrest	4
and	0
death	3
associated	0
with	0
intramuscular	0
administration	0
of	0
midazolam	1
.	0
Information	0
regarding	0
midazolam	1
use	0
is	0
reviewed	0
to	0
provide	0
recommendation	0
for	0
safe	0
administration	0
.	0
Myasthenia	3
gravis	4
presenting	0
as	0
weakness	0
after	0
magnesium	1
administration	0
.	0
We	0
studied	0
a	0
patient	0
with	0
no	0
prior	0
history	0
of	0
neuromuscular	3
disease	4
who	0
became	0
virtually	0
quadriplegic	3
after	0
parenteral	0
magnesium	1
administration	0
for	0
preeclampsia	3
.	0
The	0
serum	0
magnesium	1
concentration	0
was	0
3	0
.	0
0	0
mEq	0
/	0
L	0
","	0
which	0
is	0
usually	0
well	0
tolerated	0
.	0
The	0
magnesium	1
was	0
stopped	0
and	0
she	0
recovered	0
over	0
a	0
few	0
days	0
.	0
While	0
she	0
was	0
weak	0
","	0
2	0
-	0
Hz	0
repetitive	0
stimulation	0
revealed	0
a	0
decrement	0
without	0
significant	0
facilitation	0
at	0
rapid	0
rates	0
or	0
after	0
exercise	0
","	0
suggesting	0
postsynaptic	3
neuromuscular	4
blockade	4
.	0
After	0
her	0
strength	0
returned	0
","	0
repetitive	0
stimulation	0
was	0
normal	0
","	0
but	0
single	0
fiber	0
EMG	0
revealed	0
increased	0
jitter	0
and	0
blocking	0
.	0
Her	0
acetylcholine	1
receptor	0
antibody	0
level	0
was	0
markedly	0
elevated	0
.	0
Although	0
paralysis	3
after	0
magnesium	1
administration	0
has	0
been	0
described	0
in	0
patients	0
with	0
known	0
myasthenia	3
gravis	4
","	0
it	0
has	0
not	0
previously	0
been	0
reported	0
to	0
be	0
the	0
initial	0
or	0
only	0
manifestation	0
of	0
the	0
disease	0
.	0
Patients	0
who	0
are	0
unusually	0
sensitive	0
to	0
the	0
neuromuscular	0
effects	0
of	0
magnesium	1
should	0
be	0
suspected	0
of	0
having	0
an	0
underlying	0
disorder	3
of	4
neuromuscular	4
transmission	4
.	0
No	0
enhancement	0
by	0
phenobarbital	1
of	0
the	0
hepatocarcinogenicity	0
of	0
a	0
choline	1
-	0
devoid	0
diet	0
in	0
the	0
rat	0
.	0
An	0
experiment	0
was	0
performed	0
to	0
test	0
whether	0
inclusion	0
of	0
phenobarbital	1
in	0
a	0
choline	1
-	0
devoid	0
diet	0
would	0
increase	0
the	0
hepatocarcinogenicity	0
of	0
the	0
diet	0
.	0
Groups	0
of	0
5	0
-	0
week	0
old	0
male	0
Fischer	0
-	0
344	0
rats	0
were	0
fed	0
for	0
7	0
-	0
25	0
months	0
semipurified	0
choline	1
-	0
devoid	0
or	0
choline	1
-	0
supplemented	0
diets	0
","	0
containing	0
or	0
not	0
0	0
.	0
6	0
%	0
phenobarbital	1
.	0
No	0
hepatic	0
preneoplastic	0
nodules	0
or	0
hepatocellular	3
carcinomas	4
developed	0
in	0
rats	0
fed	0
the	0
plain	0
choline	1
-	0
supplemented	0
diet	0
","	0
while	0
one	0
preneoplastic	0
nodule	0
and	0
one	0
hepatocellular	3
carcinoma	4
developed	0
in	0
two	0
rats	0
fed	0
the	0
same	0
diet	0
containing	0
phenobarbital	1
.	0
The	0
incidence	0
of	0
preneoplastic	0
nodules	0
and	0
of	0
hepatocellular	3
carcinomas	4
was	0
10	0
%	0
and	0
37	0
%	0
","	0
respectively	0
","	0
in	0
rats	0
fed	0
the	0
plain	0
choline	1
-	0
devoid	0
diet	0
","	0
and	0
17	0
%	0
and	0
30	0
%	0
","	0
in	0
rats	0
fed	0
the	0
phenobarbital	1
-	0
containing	0
choline	1
-	0
devoid	0
diet	0
.	0
The	0
results	0
evinced	0
no	0
enhancement	0
of	0
the	0
hepatocarcinogenicity	0
of	0
the	0
choline	1
-	0
devoid	0
diet	0
by	0
phenobarbital	1
.	0
Sporadic	0
neoplastic	0
lesions	0
were	0
observed	0
in	0
organs	0
other	0
than	0
the	0
liver	0
of	0
some	0
of	0
the	0
animals	0
","	0
irrespective	0
of	0
the	0
diet	0
fed	0
.	0
0n	0
two	0
paradoxical	0
side	0
-	0
effects	0
of	0
prednisolone	1
in	0
rats	0
","	0
ribosomal	0
RNA	0
biosyntheses	0
","	0
and	0
a	0
mechanism	0
of	0
action	0
.	0
Liver	3
enlargement	4
and	0
muscle	3
wastage	4
occurred	0
in	0
Wistar	0
rats	0
following	0
the	0
subcutaneous	0
administration	0
of	0
prednisolone	1
.	0
In	0
the	0
liver	0
both	0
the	0
content	0
of	0
RNA	0
and	0
the	0
biosynthesis	0
of	0
ribosomal	0
RNA	0
increased	0
while	0
both	0
the	0
RNA	0
content	0
and	0
ribosomal	0
RNA	0
biosynthesis	0
were	0
reduced	0
in	0
the	0
gastrocnemius	0
muscle	0
.	0
It	0
is	0
suggested	0
that	0
the	0
drug	0
acted	0
in	0
a	0
selective	0
and	0
tissue	0
-	0
specific	0
manner	0
to	0
enhance	0
ribosomal	0
RNA	0
synthesis	0
in	0
the	0
liver	0
and	0
depress	0
such	0
synthesis	0
in	0
the	0
muscle	0
.	0
This	0
view	0
supports	0
the	0
contention	0
that	0
the	0
liver	0
and	0
muscle	0
are	0
independent	0
sites	0
of	0
prednisolone	1
action	0
.	0
Differential	0
effects	0
of	0
gamma	1
-	2
hexachlorocyclohexane	2
(	0
lindane	1
)	0
on	0
pharmacologically	0
-	0
induced	0
seizures	3
.	0
Gamma	1
-	2
hexachlorocyclohexane	2
(	0
gamma	1
-	2
HCH	2
)	0
","	0
the	0
active	0
ingredient	0
of	0
the	0
insecticide	0
lindane	1
","	0
has	0
been	0
shown	0
to	0
decrease	0
seizure	3
threshold	0
to	0
pentylenetrazol	0
(	0
PTZ	1
)	0
3	0
h	0
after	0
exposure	0
to	0
gamma	1
-	2
HCH	2
and	0
conversely	0
increase	0
threshold	0
to	0
PTZ	1
-	0
induced	0
seizures	3
24	0
h	0
after	0
exposure	0
to	0
gamma	1
-	2
HCH	2
(	0
Vohland	0
et	0
al	0
.	0
1981	0
)	0
.	0
In	0
this	0
study	0
","	0
the	0
severity	0
of	0
response	0
to	0
other	0
seizure	3
-	0
inducing	0
agents	0
was	0
tested	0
in	0
mice	0
1	0
and	0
24	0
h	0
after	0
intraperitoneal	0
administration	0
of	0
80	0
mg	0
/	0
kg	0
gamma	1
-	2
HCH	2
.	0
0ne	0
hour	0
after	0
the	0
administration	0
of	0
gamma	1
-	2
HCH	2
","	0
the	0
activity	0
of	0
seizure	3
-	0
inducing	0
agents	0
was	0
increased	0
","	0
regardless	0
of	0
their	0
mechanism	0
","	0
while	0
24	0
h	0
after	0
gamma	1
-	2
HCH	2
a	0
differential	0
response	0
was	0
observed	0
.	0
Seizure	3
activity	0
due	0
to	0
PTZ	1
and	0
picrotoxin	1
(	0
PTX	1
)	0
was	0
significantly	0
decreased	0
;	0
however	0
","	0
seizure	3
activity	0
due	0
to	0
3	1
-	2
mercaptopropionic	2
acid	2
(	0
MPA	1
)	0
","	0
bicuculline	1
(	0
BCC	1
)	0
","	0
methyl	1
6	2
","	2
7	2
-	2
dimethoxy	2
-	2
4	2
-	2
ethyl	2
-	2
B	2
-	2
carboline	2
-	2
3	2
-	2
carboxylate	2
(	0
DMCM	1
)	0
","	0
or	0
strychnine	1
(	0
STR	1
)	0
was	0
not	0
different	0
from	0
control	0
.	0
In	0
vitro	0
","	0
gamma	1
-	2
HCH	2
","	0
pentylenetetrazol	1
and	0
picrotoxin	1
were	0
shown	0
to	0
inhibit	0
3H	1
-	2
TB0B	2
binding	0
in	0
mouse	0
whole	0
brain	0
","	0
with	0
IC50	0
values	0
of	0
4	0
.	0
6	0
","	0
404	0
and	0
9	0
.	0
4	0
microM	0
","	0
respectively	0
.	0
MPA	1
","	0
BCC	1
","	0
DMCM	1
","	0
and	0
STR	1
showed	0
no	0
inhibition	0
of	0
3H	1
-	2
TB0B	2
(	0
t	1
-	2
butyl	2
bicyclo	2
-	2
orthobenzoate	2
)	0
binding	0
at	0
concentrations	0
of	0
100	0
micron	0
.	0
The	0
pharmacological	0
challenge	0
data	0
suggest	0
that	0
tolerance	0
may	0
occur	0
to	0
seizure	3
activity	0
induced	0
by	0
PTZ	1
and	0
PTX	1
24	0
h	0
after	0
gamma	1
-	2
HCH	2
","	0
since	0
the	0
response	0
to	0
only	0
these	0
two	0
seizure	3
-	0
inducing	0
agents	0
is	0
decreased	0
.	0
The	0
in	0
vitro	0
data	0
suggest	0
that	0
the	0
site	0
responsible	0
for	0
the	0
decrease	0
in	0
seizure	3
activity	0
24	0
h	0
after	0
gamma	1
-	2
HCH	2
may	0
be	0
the	0
GABA	1
-	0
A	0
receptor	0
-	0
linked	0
chloride	0
channel	0
.	0
Tolerance	0
and	0
antiviral	0
effect	0
of	0
ribavirin	1
in	0
patients	0
with	0
Argentine	3
hemorrhagic	4
fever	4
.	0
Tolerance	0
and	0
antiviral	0
effect	0
of	0
ribavirin	1
was	0
studied	0
in	0
6	0
patients	0
with	0
Argentine	3
hemorrhagic	4
fever	4
(	0
AHF	3
)	0
of	0
more	0
than	0
8	0
days	0
of	0
evolution	0
.	0
Administration	0
of	0
ribavirin	1
resulted	0
in	0
a	0
neutralization	0
of	0
viremia	3
and	0
a	0
drop	0
of	0
endogenous	0
interferon	0
titers	0
.	0
The	0
average	0
time	0
of	0
death	3
was	0
delayed	0
.	0
A	0
reversible	0
anemia	3
was	0
the	0
only	0
adverse	0
effect	0
observed	0
.	0
From	0
these	0
results	0
","	0
we	0
conclude	0
that	0
ribavirin	1
has	0
an	0
antiviral	0
effect	0
in	0
advanced	0
cases	0
of	0
AHF	3
","	0
and	0
that	0
anemia	3
","	0
the	0
only	0
secondary	0
reaction	0
observed	0
","	0
can	0
be	0
easily	0
managed	0
.	0
The	0
possible	0
beneficial	0
effect	0
of	0
ribavirin	1
during	0
the	0
initial	0
days	0
of	0
AHF	3
is	0
discussed	0
.	0
Is	0
the	0
treatment	0
of	0
scabies	3
hazardous	0
?	0
Treatment	0
for	0
scabies	3
is	0
usually	0
initiated	0
by	0
general	0
practitioners	0
;	0
most	0
consider	0
lindane	1
(	0
gamma	1
benzene	2
hexachloride	2
)	0
the	0
treatment	0
of	0
choice	0
.	0
Lindane	1
is	0
also	0
widely	0
used	0
as	0
an	0
agricultural	0
and	0
industrial	0
pesticide	0
","	0
and	0
as	0
a	0
result	0
the	0
toxic	0
profile	0
of	0
this	0
insecticide	0
is	0
well	0
understood	0
.	0
Evidence	0
is	0
accumulating	0
that	0
lindane	1
can	0
be	0
toxic	3
to	4
the	4
central	4
nervous	4
system	4
and	0
may	0
be	0
associated	0
with	0
aplastic	3
anaemia	4
.	0
Preparations	0
containing	0
lindane	1
continue	0
to	0
be	0
sold	0
over	0
the	0
counter	0
and	0
may	0
represent	0
a	0
hazard	0
to	0
poorly	0
informed	0
patients	0
.	0
This	0
literature	0
review	0
suggests	0
that	0
general	0
practitioners	0
should	0
prescribe	0
scabicides	0
with	0
increased	0
caution	0
for	0
certain	0
at	0
-	0
risk	0
groups	0
","	0
and	0
give	0
adequate	0
warnings	0
regarding	0
potential	0
toxicity	3
.	0
Mouse	0
strain	0
-	0
dependent	0
effect	0
of	0
amantadine	1
on	0
motility	0
and	0
brain	0
biogenic	0
amines	1
.	0
The	0
effect	0
of	0
amantadine	1
hydrochloride	2
","	0
injected	0
i	0
.	0
p	0
.	0
in	0
6	0
increments	0
of	0
100	0
mg	0
/	0
kg	0
each	0
over	0
30	0
hr	0
","	0
on	0
mouse	0
motility	0
and	0
whole	0
brain	0
content	0
of	0
selected	0
biogenic	0
amines	1
and	0
major	0
metabolites	0
was	0
studied	0
in	0
4	0
strains	0
of	0
mice	0
.	0
These	0
were	0
the	0
albino	0
Sprague	0
-	0
Dawley	0
ICR	0
and	0
BALB	0
/	0
C	0
","	0
the	0
black	0
C57BL	0
/	0
6	0
and	0
the	0
brown	0
CDF	0
-	0
I	0
mouse	0
strains	0
.	0
Amantadine	1
treatment	0
produced	0
a	0
biphasic	0
effect	0
on	0
mouse	0
motility	0
.	0
The	0
initial	0
dose	0
of	0
amantadine	1
depressed	3
locomotor	0
activity	0
in	0
all	0
mouse	0
strains	0
studied	0
with	0
the	0
BALB	0
/	0
C	0
mice	0
being	0
the	0
most	0
sensitive	0
.	0
Subsequent	0
amantadine	1
treatments	0
produced	0
enhancement	0
of	0
motility	0
from	0
corresponding	0
control	0
in	0
all	0
mouse	0
strains	0
with	0
the	0
BALB	0
/	0
C	0
mice	0
being	0
the	0
least	0
sensitive	0
.	0
The	0
locomotor	0
activity	0
was	0
decreased	0
from	0
corresponding	0
controls	0
in	0
all	0
strains	0
studied	0
","	0
except	0
for	0
the	0
ICR	0
mice	0
","	0
during	0
an	0
overnight	0
drug	0
-	0
free	0
period	0
following	0
the	0
fourth	0
amantadine	1
treatment	0
.	0
Readministration	0
of	0
amantadine	1
","	0
after	0
a	0
drug	0
-	0
free	0
overnight	0
period	0
","	0
increased	0
motility	0
from	0
respective	0
saline	0
control	0
in	0
all	0
strains	0
with	0
exception	0
of	0
the	0
BALB	0
/	0
C	0
mice	0
where	0
suppression	3
of	4
motility	4
occurred	0
.	0
Treatment	0
with	0
amantadine	1
did	0
not	0
alter	0
whole	0
brain	0
dopamine	1
levels	0
but	0
decreased	0
the	0
amounts	0
of	0
3	1
","	2
4	2
-	2
dihydroxyphenylacetic	2
acid	2
in	0
the	0
BALB	0
/	0
C	0
mice	0
compared	0
to	0
saline	0
control	0
.	0
Conversely	0
","	0
brain	0
normetanephrine	1
concentration	0
was	0
increased	0
from	0
saline	0
control	0
by	0
amantadine	1
in	0
the	0
BALB	0
/	0
C	0
mice	0
.	0
The	0
results	0
suggest	0
a	0
strain	0
-	0
dependent	0
effect	0
of	0
amantadine	1
on	0
motility	0
and	0
indicate	0
a	0
differential	0
response	0
to	0
the	0
acute	0
and	0
multiple	0
dose	0
regimens	0
used	0
.	0
The	0
BALB	0
/	0
C	0
mouse	0
was	0
the	0
most	0
sensitive	0
strain	0
and	0
could	0
serve	0
as	0
the	0
strain	0
of	0
choice	0
for	0
evaluating	0
the	0
side	0
effects	0
of	0
amantadine	1
.	0
The	0
biochemical	0
results	0
of	0
brain	0
biogenic	0
amines	1
of	0
BALB	0
/	0
C	0
mouse	0
strain	0
suggest	0
a	0
probable	0
decrease	0
of	0
catecholamine	1
turnover	0
rate	0
and	0
/	0
or	0
metabolism	0
by	0
monoamine	0
oxidase	0
and	0
a	0
resulting	0
increase	0
in	0
0	0
-	0
methylation	0
of	0
norepinephrine	1
which	0
may	0
account	0
for	0
a	0
behavioral	3
depression	4
caused	0
by	0
amantadine	1
in	0
the	0
BALB	0
/	0
C	0
mice	0
.	0
Chloroacetaldehyde	1
and	0
its	0
contribution	0
to	0
urotoxicity	0
during	0
treatment	0
with	0
cyclophosphamide	1
or	0
ifosfamide	1
.	0
An	0
experimental	0
study	0
/	0
short	0
communication	0
.	0
Based	0
on	0
clinical	0
data	0
","	0
indicating	0
that	0
chloroacetaldehyde	1
(	0
CAA	1
)	0
is	0
an	0
important	0
metabolite	0
of	0
oxazaphosphorine	0
cytostatics	0
","	0
an	0
experimental	0
study	0
was	0
carried	0
out	0
in	0
order	0
to	0
elucidate	0
the	0
role	0
of	0
CAA	1
in	0
the	0
development	0
of	0
hemorrhagic	3
cystitis	4
.	0
The	0
data	0
demonstrate	0
that	0
CAA	1
after	0
i	0
.	0
v	0
.	0
administration	0
does	0
not	0
contribute	0
to	0
bladder	3
damage	4
.	0
When	0
instilled	0
directly	0
into	0
the	0
bladder	0
","	0
CAA	1
exerts	0
urotoxic	0
effects	0
","	0
it	0
is	0
","	0
however	0
","	0
susceptible	0
to	0
detoxification	0
with	0
mesna	1
.	0
Source	0
of	0
pain	3
and	0
primitive	0
dysfunction	0
in	0
migraine	3
:	0
an	0
identical	0
site	0
?	0
Twenty	0
common	0
migraine	3
patients	0
received	0
a	0
one	0
sided	0
frontotemporal	0
application	0
of	0
nitroglycerin	1
(	0
10	0
patients	0
)	0
or	0
placebo	0
ointment	0
(	0
10	0
patients	0
)	0
in	0
a	0
double	0
blind	0
study	0
.	0
Early	0
onset	0
migraine	3
attacks	0
were	0
induced	0
by	0
nitroglycerin	1
in	0
seven	0
out	0
of	0
10	0
patients	0
versus	0
no	0
patient	0
in	0
the	0
placebo	0
group	0
.	0
Subsequently	0
20	0
migraine	3
patients	0
","	0
who	0
developed	0
an	0
early	0
onset	0
attack	0
with	0
frontotemporal	0
nitroglycerin	1
","	0
received	0
the	0
drug	0
in	0
a	0
second	0
induction	0
test	0
at	0
other	0
body	0
areas	0
.	0
No	0
early	0
onset	0
migraine	3
was	0
observed	0
.	0
Thus	0
the	0
migraine	3
-	0
inducing	0
effect	0
of	0
nitroglycerin	1
seems	0
to	0
depend	0
on	0
direct	0
stimulation	0
of	0
the	0
habitual	0
site	0
of	0
pain	3
","	0
suggesting	0
that	0
the	0
frontotemporal	0
region	0
is	0
of	0
crucial	0
importance	0
in	0
the	0
development	0
of	0
a	0
migraine	3
crisis	0
.	0
This	0
is	0
not	0
consistent	0
with	0
a	0
CNS	0
origin	0
of	0
migraine	3
attack	0
.	0
Hypersensitivity	3
to	0
carbamazepine	1
presenting	0
with	0
a	0
leukemoid	3
reaction	4
","	0
eosinophilia	3
","	0
erythroderma	3
","	0
and	0
renal	3
failure	4
.	0
We	0
report	0
a	0
patient	0
in	0
whom	0
hypersensitivity	3
to	0
carbamazepine	1
presented	0
with	0
generalized	0
erythroderma	3
","	0
a	0
severe	0
leukemoid	3
reaction	4
","	0
eosinophilia	3
","	0
hyponatremia	3
","	0
and	0
renal	3
failure	4
.	0
This	0
is	0
the	0
first	0
report	0
of	0
such	0
an	0
unusual	0
reaction	0
to	0
carbamazepine	1
.	0
Fluoxetine	1
-	0
induced	0
akathisia	3
:	0
clinical	0
and	0
theoretical	0
implications	0
.	0
Five	0
patients	0
receiving	0
fluoxetine	1
for	0
the	0
treatment	0
of	0
obsessive	3
compulsive	4
disorder	4
or	0
major	3
depression	4
developed	0
akathisia	3
.	0
The	0
typical	0
fluoxetine	1
-	0
induced	0
symptoms	0
of	0
restlessness	0
","	0
constant	0
pacing	0
","	0
purposeless	0
movements	0
of	0
the	0
feet	0
and	0
legs	0
","	0
and	0
marked	0
anxiety	3
were	0
indistinguishable	0
from	0
those	0
of	0
neuroleptic	0
-	0
induced	0
akathisia	3
.	0
Three	0
patients	0
who	0
had	0
experienced	0
neuroleptic	0
-	0
induced	0
akathisia	3
in	0
the	0
past	0
reported	0
that	0
the	0
symptoms	0
of	0
fluoxetine	1
-	0
induced	0
akathisia	3
were	0
identical	0
","	0
although	0
somewhat	0
milder	0
.	0
Akathisia	3
appeared	0
to	0
be	0
a	0
common	0
side	0
effect	0
of	0
fluoxetine	1
and	0
generally	0
responded	0
well	0
to	0
treatment	0
with	0
the	0
beta	0
-	0
adrenergic	0
antagonist	0
propranolol	1
","	0
dose	0
reduction	0
","	0
or	0
both	0
.	0
The	0
authors	0
suggest	0
that	0
fluoxetine	1
-	0
induced	0
akathisia	3
may	0
be	0
caused	0
by	0
serotonergically	0
mediated	0
inhibition	0
of	0
dopaminergic	0
neurotransmission	0
and	0
that	0
the	0
pathophysiology	0
of	0
fluoxetine	1
-	0
induced	0
akathisia	3
and	0
tricyclic	0
antidepressant	1
-	0
induced	0
"	0
jitteriness	0
"	0
may	0
be	0
identical	0
.	0
Effect	0
of	0
converting	0
enzyme	0
inhibition	0
on	0
the	0
course	0
of	0
adriamycin	1
-	0
induced	0
nephropathy	3
.	0
The	0
effect	0
of	0
the	0
converting	0
enzyme	0
inhibitor	0
(	0
CEI	0
)	0
enalapril	1
was	0
assessed	0
in	0
Munich	0
-	0
Wistar	0
rats	0
with	0
established	0
adriamycin	1
nephrosis	3
.	0
Rats	0
were	0
given	0
a	0
single	0
dose	0
of	0
adriamycin	1
and	0
one	0
month	0
later	0
divided	0
into	0
four	0
groups	0
matched	0
for	0
albuminuria	3
","	0
blood	0
pressure	0
","	0
and	0
plasma	0
albumin	0
concentration	0
.	0
Groups	0
1	0
and	0
3	0
remained	0
untreated	0
while	0
groups	0
2	0
and	0
4	0
received	0
enalapril	1
.	0
Groups	0
1	0
and	0
2	0
underwent	0
micropuncture	0
studies	0
after	0
10	0
days	0
.	0
These	0
short	0
-	0
term	0
studies	0
showed	0
that	0
enalapril	1
reduced	0
arterial	0
blood	0
pressure	0
(	0
101	0
+	0
/	0
-	0
2	0
vs	0
.	0
124	0
+	0
/	0
-	0
3	0
mm	0
Hg	0
","	0
group	0
2	0
vs	0
.	0
1	0
","	0
P	0
less	0
than	0
0	0
.	0
5	0
)	0
and	0
glomerular	0
capillary	0
pressure	0
(	0
54	0
+	0
/	0
-	0
1	0
vs	0
.	0
61	0
+	0
/	0
-	0
2	0
mm	0
Hg	0
","	0
P	0
less	0
than	0
0	0
.	0
5	0
)	0
without	0
reducing	0
albuminuria	3
(	0
617	0
+	0
/	0
-	0
50	0
vs	0
.	0
570	0
+	0
/	0
-	0
47	0
mg	0
/	0
day	0
)	0
or	0
GFR	0
(	0
1	0
.	0
3	0
+	0
/	0
-	0
0	0
.	0
4	0
vs	0
.	0
1	0
.	0
4	0
+	0
/	0
-	0
0	0
.	0
11	0
ml	0
/	0
min	0
)	0
.	0
Groups	0
3	0
and	0
4	0
were	0
studied	0
at	0
four	0
and	0
at	0
six	0
months	0
to	0
assess	0
the	0
effect	0
of	0
enalapril	1
on	0
progression	0
of	0
renal	3
injury	4
in	0
adriamycin	1
nephrosis	3
.	0
Chronic	0
enalapril	1
treatment	0
reduced	0
blood	0
pressure	0
without	0
reducing	0
albuminuria	3
in	0
group	0
4	0
.	0
Untreated	0
group	0
3	0
rats	0
exhibited	0
a	0
progressive	0
reduction	0
in	0
GFR	0
(	0
0	0
.	0
35	0
+	0
/	0
-	0
0	0
.	0
8	0
ml	0
/	0
min	0
at	0
4	0
months	0
","	0
0	0
.	0
27	0
+	0
/	0
-	0
0	0
.	0
7	0
ml	0
/	0
min	0
at	0
6	0
months	0
)	0
.	0
Enalapril	1
treatment	0
blunted	0
but	0
did	0
not	0
prevent	0
reduction	0
in	0
GFR	0
in	0
group	0
4	0
(	0
0	0
.	0
86	0
+	0
/	0
-	0
0	0
.	0
15	0
ml	0
/	0
min	0
at	0
4	0
months	0
","	0
0	0
.	0
69	0
+	0
/	0
-	0
0	0
.	0
13	0
ml	0
/	0
min	0
at	0
6	0
months	0
","	0
both	0
P	0
less	0
than	0
0	0
.	0
5	0
vs	0
.	0
group	0
3	0
)	0
.	0
Reduction	0
in	0
GFR	0
was	0
associated	0
with	0
the	0
development	0
of	0
glomerular	3
sclerosis	4
in	0
both	0
treated	0
and	0
untreated	0
rats	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0
Clotiazepam	1
-	0
induced	0
acute	0
hepatitis	3
.	0
We	0
report	0
the	0
case	0
of	0
a	0
patient	0
who	0
developed	0
acute	0
hepatitis	3
with	0
extensive	3
hepatocellular	4
necrosis	4
","	0
7	0
months	0
after	0
the	0
onset	0
of	0
administration	0
of	0
clotiazepam	1
","	0
a	0
thienodiazepine	1
derivative	0
.	0
Clotiazepam	1
withdrawal	0
was	0
followed	0
by	0
prompt	0
recovery	0
.	0
The	0
administration	0
of	0
several	0
benzodiazepines	1
","	0
chemically	0
related	0
to	0
clotiazepam	1
","	0
did	0
not	0
interfere	0
with	0
recovery	0
and	0
did	0
not	0
induce	0
any	0
relapse	0
of	0
hepatitis	3
.	0
This	0
observation	0
shows	0
that	0
clotiazepam	1
can	0
induce	0
acute	0
hepatitis	3
and	0
suggests	0
that	0
there	0
is	0
no	0
cross	0
hepatotoxicity	3
between	0
clotiazepam	1
and	0
several	0
benzodiazepines	1
.	0
5	1
-	2
azacytidine	2
potentiates	0
initiation	3
induced	4
by	4
carcinogens	4
in	0
rat	0
liver	0
.	0
To	0
test	0
the	0
validity	0
of	0
the	0
hypothesis	0
that	0
hypomethylation	0
of	0
DNA	0
plays	0
an	0
important	0
role	0
in	0
the	0
initiation	3
of	4
carcinogenic	4
process	4
","	0
5	1
-	2
azacytidine	2
(	0
5	1
-	2
AzC	2
)	0
(	0
10	0
mg	0
/	0
kg	0
)	0
","	0
an	0
inhibitor	0
of	0
DNA	0
methylation	0
","	0
was	0
given	0
to	0
rats	0
during	0
the	0
phase	0
of	0
repair	0
synthesis	0
induced	0
by	0
the	0
three	0
carcinogens	0
","	0
benzo	1
[	2
a	2
]	2
-	2
pyrene	2
(	0
200	0
mg	0
/	0
kg	0
)	0
","	0
N	1
-	2
methyl	2
-	2
N	2
-	2
nitrosourea	2
(	0
60	0
mg	0
/	0
kg	0
)	0
and	0
1	1
","	2
2	2
-	2
dimethylhydrazine	2
(	0
1	1
","	2
2	2
-	2
DMH	2
)	0
(	0
100	0
mg	0
/	0
kg	0
)	0
.	0
The	0
initiated	0
hepatocytes	0
in	0
the	0
liver	0
were	0
assayed	0
as	0
the	0
gamma	0
-	0
glutamyltransferase	0
(	0
gamma	0
-	0
GT	0
)	0
positive	0
foci	0
formed	0
following	0
a	0
2	0
-	0
week	0
selection	0
regimen	0
consisting	0
of	0
dietary	0
0	0
.	0
2	0
%	0
2	1
-	2
acetylaminofluorene	2
coupled	0
with	0
a	0
necrogenic	0
dose	0
of	0
CCl4	1
.	0
The	0
results	0
obtained	0
indicate	0
that	0
with	0
all	0
three	0
carcinogens	0
","	0
administration	0
of	0
5	1
-	2
AzC	2
during	0
repair	0
synthesis	0
increased	0
the	0
incidence	0
of	0
initiated	0
hepatocytes	0
","	0
for	0
example	0
10	0
-	0
20	0
foci	0
/	0
cm2	0
in	0
5	1
-	2
AzC	2
and	0
carcinogen	0
-	0
treated	0
rats	0
compared	0
with	0
3	0
-	0
5	0
foci	0
/	0
cm2	0
in	0
rats	0
treated	0
with	0
carcinogen	0
only	0
.	0
Administration	0
of	0
[	1
3H	2
]	2
-	2
5	2
-	2
azadeoxycytidine	2
during	0
the	0
repair	0
synthesis	0
induced	0
by	0
1	1
","	2
2	2
-	2
DMH	2
further	0
showed	0
that	0
0	0
.	0
19	0
mol	0
%	0
of	0
cytosine	1
residues	0
in	0
DNA	0
were	0
substituted	0
by	0
the	0
analogue	0
","	0
indicating	0
that	0
incorporation	0
of	0
5	1
-	2
AzC	2
occurs	0
during	0
repair	0
synthesis	0
.	0
In	0
the	0
absence	0
of	0
the	0
carcinogen	0
","	0
5	1
-	2
AzC	2
given	0
after	0
a	0
two	0
thirds	0
partial	0
hepatectomy	0
","	0
when	0
its	0
incorporation	0
should	0
be	0
maximum	0
","	0
failed	0
to	0
induce	0
any	0
gamma	0
-	0
GT	0
positive	0
foci	0
.	0
The	0
results	0
suggest	0
that	0
hypomethylation	0
of	0
DNA	0
per	0
se	0
may	0
not	0
be	0
sufficient	0
for	0
initiation	0
.	0
Perhaps	0
two	0
events	0
might	0
be	0
necessary	0
for	0
initiation	0
","	0
the	0
first	0
caused	0
by	0
the	0
carcinogen	0
and	0
a	0
second	0
involving	0
hypomethylation	0
of	0
DNA	0
.	0
Antihypertensive	0
drugs	0
and	0
depression	3
:	0
a	0
reappraisal	0
.	0
Eighty	0
-	0
nine	0
new	0
referral	0
hypertensive	3
out	0
-	0
patients	0
and	0
46	0
new	0
referral	0
non	0
-	0
hypertensive	3
chronically	0
physically	0
ill	0
out	0
-	0
patients	0
completed	0
a	0
mood	0
rating	0
scale	0
at	0
regular	0
intervals	0
for	0
one	0
year	0
.	0
The	0
results	0
showed	0
a	0
high	0
prevalence	0
of	0
depression	3
in	0
both	0
groups	0
of	0
patients	0
","	0
with	0
no	0
preponderance	0
in	0
the	0
hypertensive	3
group	0
.	0
Hypertensive	3
patients	0
with	0
psychiatric	3
histories	0
had	0
a	0
higher	0
prevalence	0
of	0
depression	3
than	0
the	0
comparison	0
patients	0
.	0
This	0
was	0
accounted	0
for	0
by	0
a	0
significant	0
number	0
of	0
depressions	3
occurring	0
in	0
methyl	1
dopa	2
treated	0
patients	0
with	0
psychiatric	3
histories	0
.	0
Chronic	3
active	4
hepatitis	4
associated	0
with	0
diclofenac	1
sodium	2
therapy	0
.	0
Diclofenac	1
sodium	2
(	0
Voltarol	1
","	0
Geigy	0
Pharmaceuticals	0
)	0
is	0
a	0
non	0
-	0
steroidal	0
anti	0
-	0
inflammatory	0
derivative	0
of	0
phenylacetic	1
acid	2
.	0
Although	0
generally	0
well	0
-	0
tolerated	0
","	0
asymptomatic	0
abnormalities	3
of	4
liver	4
function	4
have	0
been	0
recorded	0
and	0
","	0
less	0
commonly	0
","	0
severe	0
hepatitis	3
induced	0
by	0
diclofenac	1
.	0
The	0
patient	0
described	0
developed	0
chronic	3
active	4
hepatitis	4
after	0
six	0
months	0
therapy	0
with	0
diclofenac	1
sodium	2
which	0
progressed	0
despite	0
the	0
withdrawal	0
of	0
the	0
drug	0
","	0
a	0
finding	0
not	0
previously	0
reported	0
.	0
Arterial	0
hypertension	3
as	0
a	0
complication	0
of	0
prolonged	0
ketoconazole	1
treatment	0
.	0
Two	0
of	0
14	0
patients	0
with	0
Cushing	3
'	4
s	4
syndrome	4
treated	0
on	0
a	0
long	0
-	0
term	0
basis	0
with	0
ketoconazole	1
developed	0
sustained	0
hypertension	3
.	0
In	0
both	0
cases	0
normal	0
plasma	0
and	0
urinary	0
free	0
cortisol	1
levels	0
had	0
been	0
achieved	0
following	0
ketoconazole	1
therapy	0
","	0
yet	0
continuous	0
blood	0
pressure	0
monitoring	0
demonstrated	0
hypertension	3
31	0
(	0
patient	0
1	0
)	0
and	0
52	0
weeks	0
(	0
patient	0
2	0
)	0
after	0
treatment	0
.	0
In	0
patient	0
1	0
","	0
plasma	0
levels	0
of	0
deoxycorticosterone	1
and	0
11	1
-	2
deoxycortisol	2
were	0
elevated	0
.	0
In	0
patient	0
2	0
","	0
in	0
addition	0
to	0
an	0
increase	0
in	0
both	0
deoxycorticosterone	1
and	0
11	1
-	2
deoxycortisol	2
levels	0
","	0
plasma	0
aldosterone	1
values	0
were	0
raised	0
","	0
with	0
a	0
concomitant	0
suppression	0
of	0
renin	0
levels	0
.	0
0ur	0
findings	0
show	0
that	0
long	0
-	0
term	0
treatment	0
with	0
high	0
doses	0
of	0
ketoconazole	1
may	0
induce	0
enzyme	0
blockade	0
leading	0
to	0
mineralocorticoid	0
-	0
related	0
hypertension	3
.	0
Effects	0
of	0
an	0
inhibitor	0
of	0
angiotensin	1
converting	0
enzyme	0
(	0
Captopril	1
)	0
on	0
pulmonary	3
and	4
renal	4
insufficiency	4
due	0
to	0
intravascular	3
coagulation	4
in	0
the	0
rat	0
.	0
Induction	0
of	0
intravascular	3
coagulation	4
and	0
inhibition	0
of	0
fibrinolysis	0
by	0
injection	0
of	0
thrombin	0
and	0
tranexamic	1
acid	2
(	0
AMCA	1
)	0
in	0
the	0
rat	0
gives	0
rise	0
to	0
pulmonary	3
and	4
renal	4
insufficiency	4
resembling	0
that	0
occurring	0
after	0
trauma	3
or	0
sepsis	3
in	0
man	0
.	0
Injection	0
of	0
Captopril	1
(	0
1	0
mg	0
/	0
kg	0
)	0
","	0
an	0
inhibitor	0
of	0
angiotensin	1
converting	0
enzyme	0
(	0
ACE	0
)	0
","	0
reduced	0
both	0
pulmonary	3
and	4
renal	4
insufficiency	4
in	0
this	0
rat	0
model	0
.	0
The	0
lung	0
weights	0
were	0
lower	0
and	0
Pa02	0
was	0
improved	0
in	0
rats	0
given	0
this	0
enzyme	0
-	0
blocking	0
agent	0
.	0
The	0
contents	0
of	0
albumin	0
in	0
the	0
lungs	0
were	0
not	0
changed	0
","	0
indicating	0
that	0
Captopril	1
did	0
not	0
influence	0
the	0
extravasation	0
of	0
protein	0
.	0
Renal	3
damage	4
as	0
reflected	0
by	0
an	0
increase	0
in	0
serum	0
urea	1
and	0
in	0
kidney	0
weight	0
was	0
prevented	0
by	0
Captopril	1
.	0
The	0
amount	0
of	0
fibrin	0
in	0
the	0
kidneys	0
was	0
also	0
considerably	0
lower	0
than	0
in	0
animals	0
which	0
received	0
thrombin	0
and	0
AMCA	1
alone	0
.	0
It	0
is	0
suggested	0
that	0
the	0
effects	0
of	0
Captopril	1
on	0
the	0
lungs	0
may	0
be	0
attributable	0
to	0
a	0
vasodilatory	0
effect	0
due	0
to	0
a	0
reduction	0
in	0
the	0
circulating	0
level	0
of	0
Angiotension	1
II	2
and	0
an	0
increase	0
in	0
prostacyclin	1
(	0
secondary	0
to	0
an	0
increase	0
in	0
bradykinin	1
)	0
.	0
Captopril	1
may	0
","	0
by	0
the	0
same	0
mechanism	0
","	0
reduce	0
the	0
increase	0
in	0
glomerular	0
filtration	0
that	0
is	0
known	0
to	0
occur	0
after	0
an	0
injection	0
of	0
thrombin	0
","	0
thereby	0
diminishing	0
the	0
aggregation	0
of	0
fibrin	0
monomers	0
in	0
the	0
glomeruli	0
","	0
with	0
the	0
result	0
that	0
less	0
fibrin	0
will	0
be	0
deposited	0
and	0
thus	0
less	0
kidney	3
damage	4
will	0
be	0
produced	0
.	0
Stroke	3
associated	0
with	0
cocaine	1
use	0
.	0
We	0
describe	0
eight	0
patients	0
in	0
whom	0
cocaine	1
use	0
was	0
related	0
to	0
stroke	3
and	0
review	0
39	0
cases	0
from	0
the	0
literature	0
.	0
Among	0
these	0
47	0
patients	0
the	0
mean	0
(	0
+	0
/	0
-	0
SD	0
)	0
age	0
was	0
32	0
.	0
5	0
+	0
/	0
-	0
12	0
.	0
1	0
years	0
;	0
76	0
%	0
(	0
34	0
/	0
45	0
)	0
were	0
men	0
.	0
Stroke	3
followed	0
cocaine	1
use	0
by	0
inhalation	0
","	0
intranasal	0
","	0
intravenous	0
","	0
and	0
intramuscular	0
routes	0
.	0
Intracranial	3
aneurysms	4
or	0
arteriovenous	3
malformations	4
were	0
present	0
in	0
17	0
of	0
32	0
patients	0
studied	0
angiographically	0
or	0
at	0
autopsy	0
;	0
cerebral	3
vasculitis	4
was	0
present	0
in	0
two	0
patients	0
.	0
Cerebral	3
infarction	4
occurred	0
in	0
10	0
patients	0
(	0
22	0
%	0
)	0
","	0
intracerebral	3
hemorrhage	4
in	0
22	0
(	0
49	0
%	0
)	0
","	0
and	0
subarachnoid	3
hemorrhage	4
in	0
13	0
(	0
29	0
%	0
)	0
.	0
These	0
data	0
indicate	0
that	0
(	0
1	0
)	0
the	0
apparent	0
incidence	0
of	0
stroke	3
related	0
to	0
cocaine	1
use	0
is	0
increasing	0
;	0
(	0
2	0
)	0
cocaine	1
-	0
associated	0
stroke	3
occurs	0
primarily	0
in	0
young	0
adults	0
;	0
(	0
3	0
)	0
stroke	3
may	0
follow	0
any	0
route	0
of	0
cocaine	1
administration	0
;	0
(	0
4	0
)	0
stroke	3
after	0
cocaine	1
use	0
is	0
frequently	0
associated	0
with	0
intracranial	3
aneurysms	4
and	0
arteriovenous	3
malformations	4
;	0
and	0
(	0
5	0
)	0
in	0
cocaine	1
-	0
associated	0
stroke	3
","	0
the	0
frequency	0
of	0
intracranial	3
hemorrhage	4
exceeds	0
that	0
of	0
cerebral	3
infarction	4
.	0
A	0
randomized	0
comparison	0
of	0
labetalol	1
and	0
nitroprusside	1
for	0
induced	0
hypotension	3
.	0
In	0
a	0
randomized	0
study	0
","	0
labetalol	1
-	0
induced	0
hypotension	3
and	0
nitroprusside	1
-	0
induced	0
hypotension	3
were	0
compared	0
in	0
20	0
patients	0
(	0
10	0
in	0
each	0
group	0
)	0
scheduled	0
for	0
major	0
orthopedic	0
procedures	0
.	0
Each	0
patient	0
was	0
subjected	0
to	0
an	0
identical	0
anesthetic	0
protocol	0
and	0
similar	0
drug	0
-	0
induced	0
reductions	3
in	4
mean	4
arterial	4
blood	4
pressure	4
(	0
BP	0
)	0
(	0
50	0
to	0
55	0
mmHg	0
)	0
.	0
Nitroprusside	0
infusion	0
was	0
associated	0
with	0
a	0
significant	0
(	0
p	0
less	0
than	0
0	0
.	0
5	0
)	0
increase	3
in	4
heart	4
rate	4
and	4
cardiac	4
output	4
;	0
rebound	0
hypertension	3
was	0
observed	0
in	0
three	0
patients	0
after	0
discontinuation	0
of	0
nitroprusside	1
.	0
Labetalol	1
administration	0
was	0
not	0
associated	0
with	0
any	0
of	0
these	0
findings	0
.	0
Arterial	0
P02	1
decreased	0
in	0
both	0
groups	0
.	0
It	0
was	0
concluded	0
that	0
labetalol	1
offers	0
advantages	0
over	0
nitroprusside	1
.	0
Sodium	1
status	0
influences	0
chronic	0
amphotericin	1
B	2
nephrotoxicity	3
in	0
rats	0
.	0
The	0
nephrotoxic	3
potential	0
of	0
amphotericin	1
B	2
(	0
5	0
mg	0
/	0
kg	0
per	0
day	0
intraperitoneally	0
for	0
3	0
weeks	0
)	0
has	0
been	0
investigated	0
in	0
salt	0
-	0
depleted	0
","	0
normal	0
-	0
salt	0
","	0
and	0
salt	0
-	0
loaded	0
rats	0
.	0
In	0
salt	0
-	0
depleted	0
rats	0
","	0
amphotericin	1
B	2
decreased	0
creatinine	1
clearance	0
linearly	0
with	0
time	0
","	0
with	0
an	0
85	0
%	0
reduction	0
by	0
week	0
3	0
.	0
In	0
contrast	0
","	0
in	0
normal	0
-	0
salt	0
rats	0
creatinine	1
clearance	0
was	0
decreased	0
but	0
to	0
a	0
lesser	0
extent	0
at	0
week	0
2	0
and	0
3	0
","	0
and	0
in	0
salt	0
-	0
loaded	0
rats	0
creatinine	1
clearance	0
did	0
not	0
change	0
for	0
2	0
weeks	0
and	0
was	0
decreased	0
by	0
43	0
%	0
at	0
week	0
3	0
.	0
All	0
rats	0
in	0
the	0
sodium	1
-	0
depleted	0
group	0
had	0
histopathological	0
evidence	0
of	0
patchy	0
tubular	0
cytoplasmic	0
degeneration	0
in	0
tubules	0
that	0
was	0
not	0
observed	0
in	0
any	0
normal	0
-	0
salt	0
or	0
salt	0
-	0
loaded	0
rat	0
.	0
Concentrations	0
of	0
amphotericin	1
B	2
in	0
plasma	0
were	0
not	0
significantly	0
different	0
among	0
the	0
three	0
groups	0
at	0
any	0
time	0
during	0
the	0
study	0
.	0
However	0
","	0
at	0
the	0
end	0
of	0
3	0
weeks	0
","	0
amphotericin	1
B	2
levels	0
in	0
the	0
kidneys	0
and	0
liver	0
were	0
significantly	0
higher	0
in	0
salt	0
-	0
depleted	0
and	0
normal	0
-	0
salt	0
rats	0
than	0
those	0
in	0
salt	0
-	0
loaded	0
rats	0
","	0
with	0
plasma	0
/	0
kidney	0
ratios	0
of	0
21	0
","	0
14	0
","	0
and	0
8	0
in	0
salt	0
-	0
depleted	0
","	0
normal	0
-	0
salt	0
","	0
and	0
salt	0
-	0
loaded	0
rats	0
","	0
respectively	0
.	0
In	0
conclusion	0
","	0
reductions	0
in	0
creatinine	1
clearance	0
and	0
renal	0
amphotericin	1
B	2
accumulation	0
after	0
chronic	0
amphotericin	1
B	2
administration	0
were	0
enhanced	0
by	0
salt	0
depletion	0
and	0
attenuated	0
by	0
sodium	1
loading	0
in	0
rats	0
.	0
Flestolol	1
:	0
an	0
ultra	0
-	0
short	0
-	0
acting	0
beta	0
-	0
adrenergic	0
blocking	0
agent	0
.	0
Flestolol	1
(	0
ACC	1
-	2
9089	2
)	0
is	0
a	0
nonselective	0
","	0
competitive	0
","	0
ultra	0
-	0
short	0
-	0
acting	0
beta	0
-	0
adrenergic	0
blocking	0
agent	0
","	0
without	0
any	0
intrinsic	0
sympathomimetic	0
activity	0
.	0
Flestolol	1
is	0
metabolized	0
by	0
plasma	0
esterases	0
and	0
has	0
an	0
elimination	0
half	0
-	0
life	0
of	0
approximately	0
6	0
.	0
5	0
minutes	0
.	0
This	0
agent	0
was	0
well	0
tolerated	0
in	0
healthy	0
volunteers	0
at	0
doses	0
up	0
to	0
100	0
micrograms	0
/	0
kg	0
/	0
min	0
.	0
In	0
long	0
-	0
term	0
infusion	0
studies	0
","	0
flestolol	1
was	0
well	0
tolerated	0
at	0
the	0
effective	0
beta	0
-	0
blocking	0
dose	0
(	0
5	0
micrograms	0
/	0
kg	0
/	0
min	0
)	0
for	0
up	0
to	0
seven	0
days	0
.	0
Flestolol	1
blood	0
concentrations	0
increased	0
linearly	0
with	0
increasing	0
dose	0
and	0
good	0
correlation	0
exists	0
between	0
blood	0
concentrations	0
of	0
flestolol	1
and	0
beta	0
-	0
adrenergic	0
blockade	0
.	0
Flestolol	1
produced	0
a	0
dose	0
-	0
dependent	0
attenuation	0
of	0
isoproterenol	1
-	0
induced	0
tachycardia	3
.	0
Electrophysiologic	0
and	0
hemodynamic	0
effects	0
of	0
flestolol	1
are	0
similar	0
to	0
those	0
of	0
other	0
beta	0
blockers	0
.	0
In	0
contrast	0
with	0
other	0
beta	0
blockers	0
","	0
flestolol	1
-	0
induced	0
effects	0
reverse	0
rapidly	0
(	0
within	0
30	0
minutes	0
)	0
following	0
discontinuation	0
because	0
of	0
its	0
short	0
half	0
-	0
life	0
.	0
Flestolol	1
effectively	0
reduced	0
heart	0
rate	0
in	0
patients	0
with	0
supraventricular	3
tachyarrhythmia	4
.	0
In	0
patients	0
with	0
unstable	3
angina	4
","	0
flestolol	1
infusion	0
was	0
found	0
to	0
be	0
safe	0
and	0
effective	0
in	0
controlling	0
chest	3
pain	4
.	0
It	0
is	0
concluded	0
that	0
flestolol	1
is	0
a	0
potent	0
","	0
well	0
-	0
tolerated	0
","	0
ultra	0
-	0
short	0
-	0
acting	0
beta	0
-	0
adrenergic	0
blocking	0
agent	0
.	0
Use	0
of	0
flestolol	1
in	0
the	0
critical	0
care	0
setting	0
is	0
currently	0
undergoing	0
investigation	0
.	0
Immunohistochemical	0
","	0
electron	0
microscopic	0
and	0
morphometric	0
studies	0
of	0
estrogen	1
-	0
induced	0
rat	0
prolactinomas	3
after	0
bromocriptine	1
treatment	0
.	0
To	0
clarify	0
the	0
effects	0
of	0
bromocriptine	1
on	0
prolactinoma	3
cells	0
in	0
vivo	0
","	0
immunohistochemical	0
","	0
ultrastructural	0
and	0
morphometrical	0
analyses	0
were	0
applied	0
to	0
estrogen	1
-	0
induced	0
rat	0
prolactinoma	3
cells	0
1	0
h	0
and	0
6	0
h	0
after	0
injection	0
of	0
bromocriptine	1
(	0
3	0
mg	0
/	0
kg	0
of	0
body	0
weight	0
)	0
.	0
0ne	0
h	0
after	0
treatment	0
","	0
serum	0
prolactin	0
levels	0
decreased	0
markedly	0
.	0
Electron	0
microscopy	0
disclosed	0
many	0
secretory	0
granules	0
","	0
slightly	0
distorted	0
rough	0
endoplasmic	0
reticulum	0
","	0
and	0
partially	0
dilated	0
Golgi	0
cisternae	0
in	0
the	0
prolactinoma	3
cells	0
.	0
Morphometric	0
analysis	0
revealed	0
that	0
the	0
volume	0
density	0
of	0
secretory	0
granules	0
increased	0
","	0
while	0
the	0
volume	0
density	0
of	0
cytoplasmic	0
microtubules	0
decreased	0
.	0
These	0
findings	0
suggest	0
that	0
lowered	0
serum	0
prolactin	0
levels	0
in	0
the	0
early	0
phase	0
of	0
bromocriptine	1
treatment	0
may	0
result	0
from	0
an	0
impaired	0
secretion	0
of	0
prolactin	0
due	0
to	0
decreasing	0
numbers	0
of	0
cytoplasmic	0
microtubules	0
.	0
At	0
6	0
h	0
after	0
injection	0
","	0
serum	0
prolactin	0
levels	0
were	0
still	0
considerably	0
lower	0
than	0
in	0
controls	0
.	0
The	0
prolactinoma	3
cells	0
at	0
this	0
time	0
were	0
well	0
granulated	0
","	0
with	0
vesiculated	0
rough	0
endoplasmic	0
reticulum	0
and	0
markedly	0
dilated	0
Golgi	0
cisternae	0
.	0
Electron	0
microscopical	0
immunohistochemistry	0
revealed	0
positive	0
reaction	0
products	0
noted	0
on	0
the	0
secretory	0
granules	0
","	0
Golgi	0
cisternae	0
","	0
and	0
endoplasmic	0
reticulum	0
of	0
the	0
untreated	0
rat	0
prolactinoma	3
cells	0
.	0
However	0
","	0
only	0
secretory	0
granules	0
showed	0
the	0
positive	0
reaction	0
products	0
for	0
prolactin	0
6	0
h	0
after	0
bromocriptine	1
treatment	0
of	0
the	0
adenoma	3
cells	0
.	0
An	0
increase	0
in	0
the	0
volume	0
density	0
of	0
secretory	0
granules	0
and	0
a	0
decrease	0
in	0
the	0
volume	0
densities	0
of	0
rough	0
endoplasmic	0
reticulum	0
and	0
microtubules	0
was	0
determined	0
by	0
morphometric	0
analysis	0
","	0
suggesting	0
that	0
bromocriptine	1
inhibits	0
protein	0
synthesis	0
as	0
well	0
as	0
bringing	0
about	0
a	0
disturbance	0
of	0
the	0
prolactin	0
secretion	0
.	0
Sulfasalazine	1
-	0
induced	0
lupus	3
erythematosus	4
.	0
Pneumonitis	3
","	0
bilateral	0
pleural	3
effusions	4
","	0
echocardiographic	0
evidence	0
of	0
cardiac	3
tamponade	4
","	0
and	0
positive	0
autoantibodies	0
developed	0
in	0
a	0
43	0
-	0
year	0
-	0
old	0
man	0
","	0
who	0
was	0
receiving	0
long	0
-	0
term	0
sulfasalazine	1
therapy	0
for	0
chronic	0
ulcerative	3
colitis	4
.	0
After	0
cessation	0
of	0
the	0
sulfasalazine	1
and	0
completion	0
of	0
a	0
six	0
-	0
week	0
course	0
of	0
corticosteroids	0
","	0
these	0
problems	0
resolved	0
over	0
a	0
period	0
of	0
four	0
to	0
six	0
months	0
.	0
It	0
is	0
suggested	0
that	0
the	0
patient	0
had	0
sulfasalazine	1
-	0
induced	0
lupus	3
","	0
which	0
manifested	0
with	0
serositis	3
and	0
pulmonary	0
parenchymal	0
involvement	0
in	0
the	0
absence	0
of	0
joint	0
symptoms	0
.	0
Physicians	0
who	0
use	0
sulfasalazine	1
to	0
treat	0
patients	0
with	0
inflammatory	3
bowel	4
disease	4
should	0
be	0
aware	0
of	0
the	0
signs	0
of	0
sulfasalazine	1
-	0
induced	0
lupus	3
syndrome	4
.	0
Chronic	0
carbamazepine	1
treatment	0
in	0
the	0
rat	0
:	0
efficacy	0
","	0
toxicity	3
","	0
and	0
effect	0
on	0
plasma	0
and	0
tissue	0
folate	1
concentrations	0
.	0
Folate	1
depletion	0
has	0
often	0
been	0
a	0
problem	0
in	0
chronic	0
antiepileptic	0
drug	0
(	0
AED	0
)	0
therapy	0
.	0
Carbamazepine	1
(	0
CBZ	1
)	0
","	0
a	0
commonly	0
used	0
AED	0
","	0
has	0
been	0
implicated	0
in	0
some	0
clinical	0
studies	0
.	0
A	0
rat	0
model	0
was	0
developed	0
to	0
examine	0
the	0
effects	0
of	0
chronic	0
CBZ	1
treatment	0
on	0
folate	1
concentrations	0
in	0
the	0
rat	0
.	0
In	0
the	0
course	0
of	0
developing	0
this	0
model	0
","	0
a	0
common	0
vehicle	0
","	0
propylene	1
glycol	2
","	0
by	0
itself	0
in	0
high	0
doses	0
","	0
was	0
found	0
to	0
exhibit	0
protective	0
properties	0
against	0
induced	0
seizures	3
and	0
inhibited	0
weight	3
gain	4
.	0
Seizures	3
induced	0
by	0
hexafluorodiethyl	1
ether	2
(	0
HFDE	1
)	0
were	0
also	0
found	0
to	0
be	0
a	0
more	0
sensitive	0
measure	0
of	0
protection	0
by	0
CBZ	1
than	0
seizures	3
induced	0
by	0
maximal	0
electroshock	0
(	0
MES	0
)	0
.	0
0ral	0
administration	0
of	0
CBZ	1
as	0
an	0
aqueous	0
suspension	0
every	0
8	0
h	0
at	0
a	0
dose	0
of	0
250	0
mg	0
/	0
kg	0
was	0
continuously	0
protective	0
against	0
HFDE	1
-	0
induced	0
seizures	3
and	0
was	0
minimally	0
toxic	0
as	0
measured	0
by	0
weight	3
gain	4
over	0
8	0
weeks	0
of	0
treatment	0
.	0
The	0
CBZ	1
levels	0
measured	0
in	0
plasma	0
and	0
brain	0
of	0
these	0
animals	0
","	0
however	0
","	0
were	0
below	0
those	0
normally	0
considered	0
protective	0
.	0
This	0
treatment	0
with	0
CBZ	1
had	0
no	0
apparent	0
adverse	0
effect	0
on	0
folate	1
concentrations	0
in	0
the	0
rat	0
","	0
and	0
","	0
indeed	0
","	0
the	0
folate	1
concentration	0
increased	0
in	0
liver	0
after	0
6	0
weeks	0
of	0
treatment	0
and	0
in	0
plasma	0
at	0
8	0
weeks	0
of	0
treatment	0
.	0
Dipyridamole	1
-	0
induced	0
myocardial	3
ischemia	4
.	0
Angina	3
and	0
ischemic	0
electrocardiographic	0
changes	0
occurred	0
after	0
administration	0
of	0
oral	0
dipyridamole	1
in	0
four	0
patients	0
awaiting	0
urgent	0
myocardial	0
revascularization	0
procedures	0
.	0
To	0
our	0
knowledge	0
","	0
this	0
has	0
not	0
previously	0
been	0
reported	0
as	0
a	0
side	0
effect	0
of	0
preoperative	0
dipyridamole	1
therapy	0
","	0
although	0
dipyridamole	1
-	0
induced	0
myocardial	3
ischemia	4
has	0
been	0
demonstrated	0
to	0
occur	0
in	0
animals	0
and	0
humans	0
with	0
coronary	3
artery	4
disease	4
.	0
Epicardial	0
coronary	0
collateral	0
vessels	0
were	0
demonstrated	0
in	0
all	0
four	0
patients	0
;	0
a	0
coronary	0
"	0
steal	0
"	0
phenomenon	0
may	0
be	0
the	0
mechanism	0
of	0
the	0
dipyridamole	1
-	0
induced	0
ischemia	3
observed	0
.	0
Inhibition	0
of	0
sympathoadrenal	0
activity	0
by	0
atrial	0
natriuretic	0
factor	0
in	0
dogs	0
.	0
In	0
six	0
conscious	0
","	0
trained	0
dogs	0
","	0
maintained	0
on	0
a	0
normal	0
sodium	1
intake	0
of	0
2	0
to	0
4	0
mEq	0
/	0
kg	0
/	0
day	0
","	0
sympathetic	0
activity	0
was	0
assessed	0
as	0
the	0
release	0
rate	0
of	0
norepinephrine	1
and	0
epinephrine	1
during	0
15	0
-	0
minute	0
i	0
.	0
v	0
.	0
infusions	0
of	0
human	0
alpha	0
-	0
atrial	0
natriuretic	0
factor	0
.	0
Mean	0
arterial	0
pressure	0
(	0
as	0
a	0
percentage	0
of	0
control	0
+	0
/	0
-	0
SEM	0
)	0
during	0
randomized	0
infusions	0
of	0
0	0
.	0
3	0
","	0
0	0
.	0
1	0
","	0
0	0
.	0
3	0
","	0
or	0
1	0
.	0
0	0
microgram	0
/	0
kg	0
/	0
min	0
was	0
99	0
+	0
/	0
-	0
1	0
","	0
95	0
+	0
/	0
-	0
1	0
(	0
p	0
less	0
than	0
0	0
.	0
5	0
)	0
","	0
93	0
+	0
/	0
-	0
1	0
(	0
p	0
less	0
than	0
0	0
.	0
1	0
)	0
","	0
or	0
79	0
+	0
/	0
-	0
6	0
%	0
(	0
p	0
less	0
than	0
0	0
.	0
1	0
)	0
","	0
respectively	0
","	0
but	0
no	0
tachycardia	3
and	0
no	0
augmentation	0
of	0
the	0
norepinephrine	1
release	0
rate	0
(	0
up	0
to	0
0	0
.	0
3	0
microgram	0
/	0
kg	0
/	0
min	0
)	0
were	0
observed	0
","	0
which	0
is	0
in	0
contrast	0
to	0
comparable	0
hypotension	3
induced	0
by	0
hydralazine	1
or	0
nitroglycerin	1
.	0
The	0
release	0
rate	0
of	0
epinephrine	1
(	0
control	0
","	0
6	0
.	0
7	0
+	0
/	0
-	0
0	0
.	0
6	0
ng	0
/	0
kg	0
/	0
min	0
)	0
declined	0
immediately	0
during	0
infusions	0
of	0
atrial	0
natriuretic	0
factor	0
to	0
a	0
minimum	0
of	0
49	0
+	0
/	0
-	0
5	0
%	0
of	0
control	0
(	0
p	0
less	0
than	0
0	0
.	0
1	0
)	0
during	0
0	0
.	0
1	0
microgram	0
/	0
kg	0
/	0
min	0
and	0
to	0
63	0
+	0
/	0
-	0
5	0
%	0
(	0
0	0
.	0
1	0
greater	0
than	0
p	0
greater	0
than	0
0	0
.	0
5	0
)	0
or	0
95	0
+	0
/	0
-	0
13	0
%	0
(	0
not	0
significant	0
)	0
during	0
0	0
.	0
3	0
or	0
1	0
.	0
0	0
microgram	0
/	0
kg	0
/	0
min	0
.	0
Steady	0
state	0
arterial	0
plasma	0
concentrations	0
of	0
atrial	0
natriuretic	0
factor	0
were	0
39	0
+	0
/	0
-	0
10	0
pg	0
/	0
ml	0
(	0
n	0
=	0
6	0
)	0
during	0
infusions	0
of	0
saline	0
and	0
284	0
+	0
/	0
-	0
24	0
pg	0
/	0
ml	0
(	0
n	0
=	0
6	0
)	0
and	0
1520	0
+	0
/	0
-	0
300	0
pg	0
/	0
ml	0
(	0
n	0
=	0
9	0
)	0
during	0
0	0
.	0
3	0
and	0
0	0
.	0
1	0
microgram	0
/	0
kg	0
/	0
min	0
infusions	0
of	0
the	0
factor	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0
Inhibition	0
of	0
immunoreactive	0
corticotropin	0
-	0
releasing	0
factor	0
secretion	0
into	0
the	0
hypophysial	0
-	0
portal	0
circulation	0
by	0
delayed	0
glucocorticoid	0
feedback	0
.	0
Nitroprusside	1
-	0
induced	0
hypotension	3
evokes	0
ACTH	0
secretion	0
which	0
is	0
primarily	0
mediated	0
by	0
enhanced	0
secretion	0
of	0
immunoreactive	0
corticotropin	0
-	0
releasing	0
factor	0
(	0
irCRF	0
)	0
into	0
the	0
hypophysial	0
-	0
portal	0
circulation	0
.	0
Portal	0
plasma	0
concentrations	0
of	0
neither	0
arginine	1
vasopressin	2
nor	0
oxytocin	1
are	0
significantly	0
altered	0
in	0
this	0
paradigm	0
.	0
Application	0
of	0
a	0
delayed	0
feedback	0
signal	0
","	0
in	0
the	0
form	0
of	0
a	0
2	0
-	0
h	0
systemic	0
corticosterone	1
infusion	0
in	0
urethane	1
-	0
anesthetized	0
rats	0
with	0
pharmacological	0
blockade	0
of	0
glucocorticoid	0
synthesis	0
","	0
is	0
without	0
effect	0
on	0
the	0
resting	0
secretion	0
of	0
arginine	1
vasopressin	2
and	0
oxytocin	1
at	0
any	0
corticosterone	1
feedback	0
dose	0
tested	0
.	0
Resting	0
irCRF	0
levels	0
are	0
suppressed	0
only	0
at	0
the	0
highest	0
corticosterone	1
infusion	0
rate	0
","	0
which	0
resulted	0
in	0
systemic	0
corticosterone	1
levels	0
of	0
40	0
micrograms	0
/	0
dl	0
.	0
Suppression	0
of	0
irCRF	0
secretion	0
in	0
response	0
to	0
nitroprusside	1
-	0
induced	0
hypotension	3
is	0
observed	0
and	0
occurs	0
at	0
a	0
plasma	0
corticosterone	1
level	0
between	0
8	0
-	0
12	0
micrograms	0
/	0
dl	0
.	0
These	0
studies	0
provide	0
further	0
evidence	0
for	0
a	0
strong	0
central	0
component	0
of	0
the	0
delayed	0
feedback	0
process	0
which	0
is	0
mediated	0
by	0
modulation	0
of	0
irCRF	0
release	0
.	0
Noradrenergic	0
involvement	0
in	0
catalepsy	3
induced	0
by	0
delta	1
9	2
-	2
tetrahydrocannabinol	2
.	0
In	0
order	0
to	0
elucidate	0
the	0
role	0
of	0
the	0
catecholaminergic	0
system	0
in	0
the	0
cataleptogenic	0
effect	0
of	0
delta	1
9	2
-	2
tetrahydrocannabinol	2
(	0
THC	1
)	0
","	0
the	0
effect	0
of	0
pretreatment	0
with	0
6	1
-	2
hydroxydopamine	2
(	0
6	1
-	2
0HDA	2
)	0
or	0
with	0
desipramine	1
and	0
6	1
-	2
0HDA	2
and	0
lesions	0
of	0
the	0
locus	0
coeruleus	0
were	0
investigated	0
in	0
rats	0
.	0
The	0
cataleptogenic	0
effect	0
of	0
THC	1
was	0
significantly	0
reduced	0
in	0
rats	0
treated	0
with	0
6	1
-	2
0HDA	2
and	0
in	0
rats	0
with	0
lesions	0
of	0
the	0
locus	0
coeruleus	0
but	0
not	0
in	0
rats	0
treated	0
with	0
desipramine	1
and	0
6	1
-	2
0HDA	2
","	0
as	0
compared	0
with	0
control	0
rats	0
.	0
0n	0
the	0
contrary	0
","	0
the	0
cataleptogenic	0
effect	0
of	0
haloperidol	1
was	0
significantly	0
reduced	0
in	0
rats	0
treated	0
with	0
desipramine	1
and	0
6	1
-	2
0HDA	2
but	0
not	0
in	0
rats	0
treated	0
with	0
6	1
-	2
0HDA	2
or	0
in	0
rats	0
with	0
lesions	0
of	0
the	0
locus	0
coeruleus	0
.	0
These	0
results	0
indicate	0
that	0
noradrenergic	0
neurons	0
have	0
an	0
important	0
role	0
in	0
the	0
manifestation	0
of	0
catalepsy	3
induced	0
by	0
THC	1
","	0
whereas	0
dopaminergic	0
neurons	0
are	0
important	0
in	0
catalepsy	3
induced	0
by	0
haloperidol	1
.	0
Reversibility	0
of	0
captopril	1
-	0
induced	0
renal	3
insufficiency	4
after	0
prolonged	0
use	0
in	0
an	0
unusual	0
case	0
of	0
renovascular	3
hypertension	4
.	0
We	0
report	0
a	0
case	0
of	0
severe	0
hypertension	3
with	0
an	0
occluded	0
renal	0
artery	0
to	0
a	0
solitary	0
kidney	0
","	0
who	0
developed	0
sudden	3
deterioration	4
of	4
renal	4
function	4
following	0
treatment	0
with	0
captopril	1
.	0
His	0
renal	0
function	0
remained	0
impaired	0
but	0
stable	0
during	0
2	0
years	0
'	0
treatment	0
with	0
captopril	1
but	0
returned	0
to	0
pre	0
-	0
treatment	0
levels	0
soon	0
after	0
cessation	0
of	0
the	0
drug	0
.	0
This	0
indicates	0
reversibility	0
in	0
captopril	1
-	0
induced	0
renal	3
failure	4
even	0
after	0
its	0
prolonged	0
use	0
and	0
suggests	0
that	0
no	0
organic	0
damage	0
occurs	0
to	0
glomerular	0
arterioles	0
following	0
chronic	0
ACE	0
inhibition	0
.	0
HMG	0
CoA	0
reductase	0
inhibitors	0
.	0
Current	0
clinical	0
experience	0
.	0
Lovastatin	1
and	0
simvastatin	1
are	0
the	0
2	0
best	0
-	0
known	0
members	0
of	0
the	0
class	0
of	0
hypolipidaemic	0
agents	0
known	0
as	0
HMG	0
CoA	0
reductase	0
inhibitors	0
.	0
Clinical	0
experience	0
with	0
lovastatin	1
includes	0
over	0
5000	0
patients	0
","	0
700	0
of	0
whom	0
have	0
been	0
treated	0
for	0
2	0
years	0
or	0
more	0
","	0
and	0
experience	0
with	0
simvastatin	1
includes	0
over	0
3500	0
patients	0
","	0
of	0
whom	0
350	0
have	0
been	0
treated	0
for	0
18	0
months	0
or	0
more	0
.	0
Lovastatin	1
has	0
been	0
marketed	0
in	0
the	0
United	0
States	0
for	0
over	0
6	0
months	0
.	0
Both	0
agents	0
show	0
substantial	0
clinical	0
efficacy	0
","	0
with	0
reductions	0
in	0
total	0
cholesterol	1
of	0
over	0
30	0
%	0
and	0
in	0
LDL	0
-	0
cholesterol	1
of	0
40	0
%	0
in	0
clinical	0
studies	0
.	0
Modest	0
increases	0
in	0
HDL	0
-	0
cholesterol	1
levels	0
of	0
about	0
10	0
%	0
are	0
also	0
reported	0
.	0
Clinical	0
tolerability	0
of	0
both	0
agents	0
has	0
been	0
good	0
","	0
with	0
fewer	0
than	0
3	0
%	0
of	0
patients	0
withdrawn	0
from	0
treatment	0
because	0
of	0
clinical	0
adverse	0
experiences	0
.	0
0phthalmological	0
examinations	0
in	0
over	0
1100	0
patients	0
treated	0
with	0
one	0
or	0
the	0
other	0
agent	0
have	0
revealed	0
no	0
evidence	0
of	0
significant	0
short	0
term	0
(	0
up	0
to	0
2	0
years	0
)	0
cataractogenic	0
potential	0
.	0
0ne	0
to	0
2	0
%	0
of	0
patients	0
have	0
elevations	0
of	0
serum	0
transaminases	0
to	0
greater	0
than	0
3	0
times	0
the	0
upper	0
limit	0
of	0
normal	0
.	0
These	0
episodes	0
are	0
asymptomatic	0
and	0
reversible	0
when	0
therapy	0
is	0
discontinued	0
.	0
Minor	0
elevations	0
of	0
creatine	1
kinase	0
levels	0
are	0
reported	0
in	0
about	0
5	0
%	0
of	0
patients	0
.	0
Myopathy	3
","	0
associated	0
in	0
some	0
cases	0
with	0
myoglobinuria	3
","	0
and	0
in	0
2	0
cases	0
with	0
transient	0
renal	3
failure	4
","	0
has	0
been	0
rarely	0
reported	0
with	0
lovastatin	1
","	0
especially	0
in	0
patients	0
concomitantly	0
treated	0
with	0
cyclosporin	1
","	0
gemfibrozil	1
or	0
niacin	1
.	0
Lovastatin	1
and	0
simvastatin	1
are	0
both	0
effective	0
and	0
well	0
-	0
tolerated	0
agents	0
for	0
lowering	0
elevated	0
levels	0
of	0
serum	0
cholesterol	1
.	0
As	0
wider	0
use	0
confirms	0
their	0
safety	0
profile	0
","	0
they	0
will	0
gain	0
increasing	0
importance	0
in	0
the	0
therapeutic	0
approach	0
to	0
hypercholesterolaemia	3
and	0
its	0
consequences	0
.	0
Hepatic	0
reactions	0
associated	0
with	0
ketoconazole	1
in	0
the	0
United	0
Kingdom	0
.	0
Ketoconazole	1
was	0
introduced	0
in	0
the	0
United	0
Kingdom	0
in	0
1981	0
.	0
By	0
November	0
1984	0
the	0
Committee	0
on	0
Safety	0
of	0
Medicines	0
had	0
received	0
82	0
reports	0
of	0
possible	0
hepatotoxicity	3
associated	0
with	0
the	0
drug	0
","	0
including	0
five	0
deaths	3
.	0
An	0
analysis	0
of	0
the	0
75	0
cases	0
that	0
had	0
been	0
adequately	0
followed	0
up	0
suggested	0
that	0
16	0
","	0
including	0
three	0
deaths	3
","	0
were	0
probably	0
related	0
to	0
treatment	0
with	0
the	0
drug	0
.	0
0f	0
the	0
remainder	0
","	0
48	0
were	0
possibly	0
related	0
to	0
treatment	0
","	0
five	0
were	0
unlikely	0
to	0
be	0
so	0
","	0
and	0
six	0
were	0
unclassifiable	0
.	0
The	0
mean	0
age	0
of	0
patients	0
in	0
the	0
16	0
probable	0
cases	0
was	0
57	0
.	0
9	0
","	0
with	0
hepatotoxicity	3
being	0
more	0
common	0
in	0
women	0
.	0
The	0
average	0
duration	0
of	0
treatment	0
before	0
the	0
onset	0
of	0
jaundice	3
was	0
61	0
days	0
.	0
None	0
of	0
these	0
well	0
validated	0
cases	0
occurred	0
within	0
the	0
first	0
10	0
days	0
after	0
treatment	0
.	0
The	0
results	0
of	0
serum	0
liver	0
function	0
tests	0
suggested	0
hepatocellular	3
injury	4
in	0
10	0
(	0
63	0
%	0
)	0
;	0
the	0
rest	0
showed	0
a	0
mixed	0
pattern	0
.	0
In	0
contrast	0
","	0
the	0
results	0
of	0
histological	0
examination	0
of	0
the	0
liver	0
often	0
showed	0
evidence	0
of	0
cholestasis	3
.	0
The	0
characteristics	0
of	0
the	0
48	0
patients	0
in	0
the	0
possible	0
cases	0
were	0
similar	0
.	0
Allergic	0
manifestations	0
such	0
as	0
rash	3
and	0
eosinophilia	3
were	0
rare	0
.	0
Hepatitis	3
was	0
usually	0
reversible	0
when	0
treatment	0
was	0
stopped	0
","	0
with	0
the	0
results	0
of	0
liver	0
function	0
tests	0
returning	0
to	0
normal	0
after	0
an	0
average	0
of	0
3	0
.	0
1	0
months	0
.	0
In	0
two	0
of	0
the	0
three	0
deaths	3
probably	0
associated	0
with	0
ketoconazole	1
treatment	0
the	0
drug	0
had	0
been	0
continued	0
after	0
the	0
onset	0
of	0
jaundice	3
and	0
other	0
symptoms	0
of	0
hepatitis	3
.	0
Clinical	0
and	0
biochemical	0
monitoring	0
at	0
regular	0
intervals	0
for	0
evidence	0
of	0
hepatitis	3
is	0
advised	0
during	0
long	0
term	0
treatment	0
with	0
ketoconazole	1
to	0
prevent	0
possible	0
serious	0
hepatic	3
injury	4
.	0
Glyburide	1
-	0
induced	0
hepatitis	3
.	0
Drug	0
-	0
induced	0
hepatotoxicity	3
","	0
although	0
common	0
","	0
has	0
been	0
reported	0
only	0
infrequently	0
with	0
sulfonylureas	1
.	0
For	0
glyburide	1
","	0
a	0
second	0
-	0
generation	0
sulfonylurea	1
","	0
only	0
two	0
brief	0
reports	0
of	0
hepatotoxicity	3
exist	0
.	0
Two	0
patients	0
with	0
type	3
II	4
diabetes	4
mellitus	4
developed	0
an	0
acute	3
hepatitis	4
-	4
like	4
syndrome	4
soon	0
after	0
initiation	0
of	0
glyburide	1
therapy	0
.	0
There	0
was	0
no	0
serologic	0
evidence	0
of	0
viral	3
infection	4
","	0
and	0
a	0
liver	0
biopsy	0
sample	0
showed	0
a	0
histologic	0
pattern	0
consistent	0
with	0
drug	3
-	4
induced	4
hepatitis	4
.	0
Both	0
patients	0
recovered	0
quickly	0
after	0
stopping	0
glyburide	1
therapy	0
and	0
have	0
remained	0
well	0
for	0
a	0
follow	0
-	0
up	0
period	0
of	0
1	0
year	0
.	0
Glyburide	1
can	0
produce	0
an	0
acute	3
hepatitis	4
-	4
like	4
illness	4
in	0
some	0
persons	0
.	0
Intracranial	0
pressure	0
increases	0
during	0
alfentanil	1
-	0
induced	0
rigidity	3
.	0
Intracranial	0
pressure	0
(	0
ICP	0
)	0
was	0
measured	0
during	0
alfentanil	1
-	0
induced	0
rigidity	3
in	0
rats	0
.	0
Ten	0
rats	0
had	0
arterial	0
","	0
central	0
venous	0
(	0
CVP	0
)	0
","	0
and	0
subdural	0
cannulae	0
inserted	0
under	0
halothane	1
anesthesia	0
.	0
The	0
animals	0
were	0
mechanically	0
ventilated	0
to	0
achieve	0
normocarbia	0
(	0
PC02	0
=	0
42	0
+	0
/	0
-	0
1	0
mmHg	0
","	0
mean	0
+	0
/	0
-	0
SE	0
)	0
.	0
Following	0
instrumentation	0
","	0
halothane	1
was	0
discontinued	0
and	0
alfentanil	1
(	0
125	0
mu	0
/	0
kg	0
)	0
administered	0
iv	0
during	0
emergence	0
from	0
halothane	1
anesthesia	0
.	0
In	0
the	0
five	0
rats	0
that	0
developed	0
somatic	3
rigidity	4
","	0
ICP	0
and	0
CVP	0
increased	0
significantly	0
above	0
baseline	0
(	0
delta	0
ICP	0
7	0
.	0
5	0
+	0
/	0
-	0
1	0
.	0
0	0
mmHg	0
","	0
delta	0
CVP	0
5	0
.	0
9	0
+	0
/	0
-	0
1	0
.	0
3	0
mmHg	0
)	0
.	0
These	0
variables	0
returned	0
to	0
baseline	0
when	0
rigidity	3
was	0
abolished	0
with	0
metocurine	1
.	0
In	0
five	0
rats	0
that	0
did	0
not	0
become	0
rigid	0
","	0
ICP	0
and	0
CVP	0
did	0
not	0
change	0
following	0
alfentanil	1
.	0
These	0
observations	0
suggest	0
that	0
rigidity	3
should	0
be	0
prevented	0
when	0
alfentanil	1
","	0
and	0
","	0
presumably	0
","	0
other	0
opiates	0
","	0
are	0
used	0
in	0
the	0
anesthetic	0
management	0
of	0
patients	0
with	0
ICP	0
problems	0
.	0
Verapamil	1
withdrawal	0
as	0
a	0
possible	0
cause	0
of	0
myocardial	3
infarction	4
in	0
a	0
hypertensive	3
woman	0
with	0
a	0
normal	0
coronary	0
angiogram	0
.	0
Verapamil	1
is	0
an	0
effective	0
and	0
relatively	0
-	0
safe	0
antihypertensive	0
drug	0
.	0
Serious	0
adverse	0
effects	0
are	0
uncommon	0
and	0
mainly	0
have	0
been	0
related	0
to	0
the	0
depression	3
of	0
cardiac	0
contractility	0
and	0
conduction	0
","	0
especially	0
when	0
the	0
drug	0
is	0
combined	0
with	0
beta	0
-	0
blocking	0
agents	0
.	0
We	0
report	0
a	0
case	0
in	0
which	0
myocardial	3
infarction	4
coincided	0
with	0
the	0
introduction	0
of	0
captopril	1
and	0
the	0
withdrawal	0
of	0
verapamil	1
in	0
a	0
previously	0
asymptomatic	0
woman	0
with	0
severe	0
hypertension	3
.	0
Possible	0
mechanisms	0
that	0
involve	0
a	0
verapamil	1
-	0
related	0
increase	0
in	0
platelet	0
and	0
/	0
or	0
vascular	0
alpha	0
2	0
-	0
adrenoreceptor	0
affinity	0
for	0
catecholamines	1
are	0
discussed	0
.	0
Haemolytic	3
-	4
uraemic	4
syndrome	4
after	0
treatment	0
with	0
metronidazole	1
.	0
This	0
paper	0
describes	0
the	0
clinical	0
features	0
of	0
six	0
children	0
who	0
developed	0
the	0
haemolytic	3
-	4
uraemic	4
syndrome	4
after	0
treatment	0
with	0
metronidazole	1
.	0
These	0
children	0
were	0
older	0
and	0
were	0
more	0
likely	0
to	0
have	0
undergone	0
recent	0
bowel	0
surgery	0
than	0
are	0
other	0
children	0
with	0
this	0
condition	0
.	0
While	0
the	0
involvement	0
of	0
metronidazole	1
in	0
the	0
aetiology	0
of	0
the	0
haemolytic	3
-	4
uraemic	4
syndrome	4
is	0
not	0
established	0
firmly	0
","	0
the	0
action	0
of	0
this	0
drug	0
in	0
sensitizing	0
tissues	0
to	0
oxidation	0
injury	0
and	0
the	0
reported	0
evidence	0
of	0
oxidation	0
changes	0
in	0
the	0
haemolytic	3
-	4
uraemic	4
syndrome	4
suggest	0
a	0
possible	0
link	0
between	0
metronidazole	1
treatment	0
and	0
some	0
cases	0
of	0
the	0
haemolytic	3
-	4
uraemic	4
syndrome	4
.	0
Adverse	0
cardiac	0
effects	0
during	0
induction	0
chemotherapy	0
treatment	0
with	0
cis	1
-	2
platin	2
and	0
5	1
-	2
fluorouracil	2
.	0
Survival	0
for	0
patients	0
with	0
advanced	0
head	3
and	4
neck	4
carcinoma	4
and	0
esophageal	3
carcinoma	4
is	0
poor	0
with	0
radiotherapy	0
and	0
/	0
or	0
surgery	0
.	0
0bviously	0
","	0
there	0
is	0
a	0
need	0
for	0
effective	0
chemotherapy	0
.	0
In	0
the	0
present	0
study	0
","	0
cis	1
-	2
platin	2
(	0
80	0
-	0
120	0
mg	0
/	0
m2BSA	0
)	0
and	0
5	1
-	2
FU	2
(	0
1000	0
mg	0
/	0
m2BSA	0
daily	0
as	0
a	0
continuous	0
infusion	0
during	0
5	0
days	0
)	0
were	0
given	0
to	0
76	0
patients	0
before	0
radiotherapy	0
and	0
surgery	0
.	0
The	0
aim	0
of	0
the	0
study	0
was	0
to	0
clarify	0
the	0
incidence	0
and	0
severity	0
of	0
adverse	0
cardiac	0
effects	0
to	0
this	0
treatment	0
.	0
Before	0
treatment	0
all	0
patients	0
had	0
a	0
cardiac	0
evaluation	0
and	0
during	0
treatment	0
serial	0
ECG	0
recordings	0
were	0
performed	0
.	0
In	0
the	0
pre	0
-	0
treatment	0
evaluation	0
","	0
signs	0
of	0
cardiovascular	3
disease	4
were	0
found	0
in	0
33	0
patients	0
(	0
43	0
%	0
)	0
.	0
During	0
treatment	0
","	0
adverse	0
cardiac	0
effects	0
were	0
observed	0
in	0
14	0
patients	0
(	0
18	0
%	0
)	0
.	0
The	0
mean	0
age	0
of	0
these	0
patients	0
was	0
the	0
same	0
as	0
for	0
the	0
entire	0
group	0
","	0
64	0
years	0
.	0
The	0
incidence	0
of	0
cardiotoxicity	3
was	0
not	0
higher	0
in	0
patients	0
with	0
signs	0
of	0
cardiovascular	3
disease	4
than	0
in	0
those	0
without	0
in	0
the	0
pre	0
-	0
treatment	0
evaluation	0
.	0
The	0
most	0
common	0
signs	0
of	0
cardiotoxicity	3
were	0
chest	3
pain	4
","	0
ST	0
-	0
T	0
wave	0
changes	0
and	0
atrial	3
fibrillation	4
.	0
This	0
was	0
followed	0
by	0
ventricular	3
fibrillation	4
in	0
one	0
patient	0
and	0
sudden	3
death	4
in	0
another	0
.	0
It	0
is	0
concluded	0
that	0
patients	0
on	0
5	1
-	2
FU	2
treatment	0
should	0
be	0
under	0
close	0
supervision	0
and	0
that	0
the	0
treatment	0
should	0
be	0
discontinued	0
if	0
chest	3
pain	4
or	0
tachyarrhythmia	3
is	0
observed	0
.	0
Death	3
from	0
chemotherapy	0
in	0
gestational	3
trophoblastic	4
disease	4
.	0
Multiple	0
cytotoxic	0
drug	0
administration	0
is	0
the	0
generally	0
accepted	0
treatment	0
of	0
patients	0
with	0
a	0
high	0
-	0
risk	0
stage	0
of	0
choriocarcinoma	3
.	0
Based	0
on	0
this	0
principle	0
a	0
27	0
-	0
year	0
old	0
woman	0
","	0
classified	0
as	0
being	0
in	0
the	0
high	0
-	0
risk	0
group	0
(	0
Goldstein	0
and	0
Berkowitz	0
score	0
:	0
11	0
)	0
","	0
was	0
treated	0
with	0
multiple	0
cytotoxic	0
drugs	0
.	0
The	0
multiple	0
drug	0
schema	0
consisted	0
of	0
:	0
Etoposide	1
16	0
.	0
213	0
","	0
Methotrexate	1
","	0
Cyclophosphamide	1
","	0
Actomycin	1
-	2
D	2
","	0
and	0
Cisplatin	1
.	0
0n	0
the	0
first	0
day	0
of	0
the	0
schedule	0
","	0
moderate	0
high	0
doses	0
of	0
Methotrexate	1
","	0
Etoposide	1
and	0
Cyclophosphamide	1
were	0
administered	0
.	0
Within	0
8	0
hours	0
after	0
initiation	0
of	0
therapy	0
the	0
patient	0
died	0
with	0
a	0
clinical	0
picture	0
resembling	0
massive	0
pulmonary	3
obstruction	4
due	0
to	0
choriocarcinomic	0
tissue	0
plugs	0
","	0
probably	0
originating	0
from	0
the	0
uterus	0
.	0
Formation	0
of	0
these	0
plugs	0
was	0
probably	0
due	0
to	0
extensive	0
tumor	3
necrosis	3
at	0
the	0
level	0
of	0
the	0
walls	0
of	0
the	0
major	0
uterine	0
veins	0
","	0
which	0
resulted	0
in	0
an	0
open	0
exchange	0
of	0
tumor	3
plugs	0
to	0
the	0
vascular	0
spaces	0
;	0
decrease	0
in	0
tumor	3
tissue	0
coherence	0
secondary	0
to	0
chemotherapy	0
may	0
have	0
further	0
contributed	0
to	0
the	0
formation	0
of	0
tumor	3
emboli	0
.	0
In	0
view	0
of	0
the	0
close	0
time	0
association	0
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the	0
start	0
of	0
chemotherapy	0
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acute	0
onset	0
of	0
massive	0
embolism	3
other	0
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","	0
such	0
as	0
spontaneous	0
necrosis	3
","	0
must	0
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less	0
likely	0
.	0
Patients	0
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pelvic	3
tumor	4
loads	0
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","	0
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existing	0
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","	0
at	0
high	0
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","	0
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-	0
hCG	0
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agressive	0
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.	0
(	0
ABSTRACT	0
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250	0
W0RDS	0
)	0
Pulmonary	0
shunt	0
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cardiovascular	0
responses	0
to	0
CPAP	0
during	0
nitroprusside	1
-	0
induced	0
hypotension	3
.	0
The	0
effects	0
of	0
continuous	0
positive	0
airway	0
pressure	0
(	0
CPAP	0
)	0
on	0
cardiovascular	0
dynamics	0
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pulmonary	0
shunt	0
(	0
QS	0
/	0
QT	0
)	0
were	0
investigated	0
in	0
12	0
dogs	0
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and	0
during	0
sodium	1
nitroprusside	2
infusion	0
that	0
decreased	0
mean	0
arterial	0
blood	0
pressure	0
40	0
-	0
50	0
per	0
cent	0
.	0
Before	0
nitroprusside	1
infusion	0
","	0
5	0
cm	0
H20	1
CPAP	0
significantly	0
","	0
P	0
less	0
than	0
.	0
5	0
","	0
decreased	0
arterial	0
blood	0
pressure	0
","	0
but	0
did	0
not	0
significantly	0
alter	0
heart	0
rate	0
","	0
cardiac	0
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","	0
systemic	0
vascular	0
resistance	0
","	0
or	0
QS	0
/	0
QT	0
.	0
Ten	0
cm	0
H20	1
CPAP	0
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nitroprusside	1
infusion	0
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a	0
further	0
decrease	3
in	4
arterial	4
blood	4
pressure	4
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heart	0
rate	0
and	0
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cardiac	4
output	4
and	0
QS	0
/	0
QT	0
.	0
Nitroprusside	1
caused	0
significant	0
decreases	3
in	4
arterial	4
blood	4
pressure	4
and	0
systemic	0
vascular	0
resistance	0
and	0
increases	0
in	0
heart	0
rate	0
","	0
but	0
did	0
not	0
change	0
cardiac	0
output	0
or	0
QS	0
/	0
QT	0
.	0
Five	0
cm	0
H20	1
CPAP	0
during	0
nitroprusside	1
did	0
not	0
further	0
alter	0
any	0
of	0
the	0
above	0
-	0
mentioned	0
variables	0
.	0
However	0
","	0
10	0
cm	0
H20	1
CPAP	0
decreased	0
arterial	0
blood	0
pressure	0
","	0
cardiac	0
output	0
","	0
and	0
QS	0
/	0
QT	0
.	0
These	0
data	0
indicate	0
that	0
nitroprusside	1
infusion	0
rates	0
that	0
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arterial	0
blood	0
pressure	0
by	0
40	0
-	0
50	0
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cent	0
do	0
not	0
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cardiac	0
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QS	0
/	0
QT	0
.	0
During	0
nitroprusside	1
infusion	0
low	0
levels	0
of	0
CPAP	0
do	0
not	0
markedly	0
alter	0
cardiovascular	0
dynamics	0
","	0
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high	0
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of	0
CPAP	0
(	0
10	0
cm	0
H20	1
)	0
","	0
while	0
decreasing	0
QS	0
/	0
QT	0
","	0
produce	0
marked	0
decreases	3
in	4
arterial	4
blood	4
pressure	4
and	4
cardiac	4
output	4
.	0
Systolic	0
pressure	0
variation	0
is	0
greater	0
during	0
hemorrhage	3
than	0
during	0
sodium	1
nitroprusside	2
-	0
induced	0
hypotension	3
in	0
ventilated	0
dogs	0
.	0
The	0
systolic	0
pressure	0
variation	0
(	0
SPV	0
)	0
","	0
which	0
is	0
the	0
difference	0
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the	0
maximal	0
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minimal	0
values	0
of	0
the	0
systolic	0
blood	0
pressure	0
(	0
SBP	0
)	0
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one	0
positive	0
-	0
pressure	0
breath	0
","	0
was	0
studied	0
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ventilated	0
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to	0
hypotension	3
.	0
Mean	0
arterial	0
pressure	0
was	0
decreased	0
to	0
50	0
mm	0
Hg	0
for	0
30	0
minutes	0
either	0
by	0
hemorrhage	3
(	0
HEM	3
","	0
n	0
=	0
7	0
)	0
or	0
by	0
continuous	0
infusion	0
of	0
sodium	1
nitroprusside	2
(	0
SNP	1
","	0
n	0
=	0
7	0
)	0
.	0
During	0
HEM	3
-	0
induced	0
hypotension	3
the	0
cardiac	0
output	0
was	0
significantly	0
lower	0
and	0
systemic	0
vascular	0
resistance	0
higher	0
compared	0
with	0
that	0
in	0
the	0
SNP	1
group	0
.	0
The	0
systemic	0
","	0
central	0
venous	0
","	0
pulmonary	0
capillary	0
wedge	0
pressures	0
","	0
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heart	0
rates	0
","	0
were	0
similar	0
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the	0
two	0
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.	0
Analysis	0
of	0
the	0
respiratory	0
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in	0
the	0
arterial	0
pressure	0
waveform	0
enabled	0
differentiation	0
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the	0
two	0
groups	0
.	0
The	0
SPV	0
during	0
hypotension	3
was	0
15	0
.	0
7	0
+	0
/	0
-	0
6	0
.	0
7	0
mm	0
Hg	0
in	0
the	0
HEM	3
group	0
","	0
compared	0
with	0
9	0
.	0
1	0
+	0
/	0
-	0
2	0
.	0
0	0
mm	0
Hg	0
in	0
the	0
SNP	1
group	0
(	0
P	0
less	0
than	0
0	0
.	0
2	0
)	0
.	0
The	0
delta	0
down	0
","	0
which	0
is	0
the	0
measure	0
of	0
decrease	0
of	0
SBP	0
after	0
a	0
mechanical	0
breath	0
","	0
was	0
20	0
.	0
3	0
+	0
/	0
-	0
8	0
.	0
4	0
and	0
10	0
.	0
1	0
+	0
/	0
-	0
3	0
.	0
8	0
mm	0
Hg	0
in	0
the	0
HEM	3
and	0
SNP	1
groups	0
","	0
respectively	0
","	0
during	0
hypotension	3
(	0
P	0
less	0
than	0
0	0
.	0
2	0
)	0
.	0
It	0
is	0
concluded	0
that	0
increases	0
in	0
the	0
SPV	0
and	0
the	0
delta	0
down	0
are	0
characteristic	0
of	0
a	0
hypotensive	3
state	0
due	0
to	0
a	0
predominant	0
decrease	0
in	0
preload	0
.	0
They	0
are	0
thus	0
more	0
important	0
during	0
absolute	0
hypovolemia	3
than	0
during	0
deliberate	0
hypotension	3
.	0
Ventricular	3
tachyarrhythmias	4
during	0
cesarean	0
section	0
after	0
ritodrine	1
therapy	0
:	0
interaction	0
with	0
anesthetics	0
.	0
This	0
case	0
illustrates	0
that	0
patients	0
receiving	0
ritodrine	1
for	0
preterm	3
labor	4
may	0
risk	0
interactions	0
between	0
the	0
residual	0
betamimetic	0
effects	0
of	0
ritodrine	1
and	0
the	0
effects	0
of	0
anesthetics	0
during	0
cesarean	0
section	0
.	0
Such	0
interactions	0
may	0
result	0
in	0
serious	0
cardiovascular	3
complications	4
even	0
after	0
cessation	0
of	0
an	0
infusion	0
of	0
ritodrine	1
.	0
Preoperative	0
assessment	0
should	0
focus	0
on	0
cardiovascular	0
status	0
and	0
serum	0
potassium	1
level	0
.	0
Delaying	0
induction	0
of	0
anesthesia	0
should	0
be	0
considered	0
whenever	0
possible	0
.	0
Careful	0
fluid	0
administration	0
and	0
cautious	0
use	0
of	0
titrated	0
doses	0
of	0
ephedrine	1
are	0
advised	0
.	0
After	0
delivery	0
of	0
the	0
infant	0
","	0
there	0
should	0
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no	0
contraindication	0
to	0
the	0
use	0
of	0
an	0
alpha	0
-	0
adrenergic	0
vasopressor	0
such	0
as	0
phenylephrine	1
to	0
treat	0
hypotensive	3
patients	0
with	0
tachycardia	3
.	0
Verapamil	1
-	0
induced	0
carbamazepine	1
neurotoxicity	3
.	0
A	0
report	0
of	0
two	0
cases	0
.	0
Two	0
patients	0
with	0
signs	0
of	0
carbamazepine	1
neurotoxicity	3
after	0
combined	0
treatment	0
with	0
verapamil	1
showed	0
complete	0
recovery	0
after	0
discontinuation	0
of	0
the	0
calcium	1
entry	0
blocker	0
.	0
Use	0
of	0
verapamil	1
in	0
combination	0
with	0
carbamazepine	1
should	0
either	0
be	0
avoided	0
or	0
prescribed	0
only	0
with	0
appropriate	0
adjustment	0
of	0
the	0
carbamazepine	1
dose	0
(	0
usually	0
reduction	0
of	0
the	0
carbamazepine	1
dose	0
by	0
one	0
half	0
)	0
.	0
Paracetamol	1
-	0
associated	0
coma	3
","	0
metabolic	3
acidosis	4
","	0
renal	3
and	4
hepatic	4
failure	4
.	0
A	0
case	0
of	0
metabolic	3
acidosis	4
","	0
acute	3
renal	4
failure	4
and	4
hepatic	4
failure	4
following	0
paracetamol	1
ingestion	0
is	0
presented	0
.	0
The	0
diagnostic	0
difficulty	0
at	0
presentation	0
is	0
highlighted	0
.	0
Continuous	0
arteriovenous	0
haemofiltration	0
proved	0
a	0
valuable	0
means	0
of	0
maintaining	0
fluid	0
and	0
electrolyte	0
balance	0
.	0
The	0
patient	0
recovered	0
.	0
Sexual	3
dysfunction	4
among	0
patients	0
with	0
arthritis	3
.	0
The	0
relationship	0
of	0
arthritis	3
and	0
sexual	3
dysfunction	4
was	0
investigated	0
among	0
169	0
patients	0
with	0
rheumatoid	3
arthritis	4
","	0
osteoarthritis	3
and	0
spondyloarthropathy	3
","	0
130	0
of	0
whom	0
were	0
pair	0
-	0
matched	0
to	0
controls	0
.	0
Assessments	0
of	0
marital	0
happiness	0
and	0
depressed	3
mood	4
were	0
also	0
made	0
using	0
the	0
CES	0
-	0
D	0
and	0
the	0
Azrin	0
Marital	0
Happiness	0
Scale	0
(	0
AMHS	0
)	0
.	0
Sexual	3
dysfunctions	4
were	0
found	0
to	0
be	0
common	0
among	0
patients	0
and	0
controls	0
","	0
the	0
majority	0
in	0
both	0
groups	0
reporting	0
one	0
or	0
more	0
dysfunctions	0
.	0
Impotence	3
was	0
more	0
common	0
among	0
male	0
patients	0
than	0
controls	0
and	0
was	0
found	0
to	0
be	0
associated	0
with	0
co	0
-	0
morbidity	0
and	0
the	0
taking	0
of	0
methotrexate	1
.	0
Depressed	3
mood	4
was	0
more	0
common	0
among	0
patients	0
and	0
was	0
associated	0
with	0
certain	0
sexual	0
difficulties	0
","	0
but	0
not	0
with	0
impotence	3
.	0
Marital	0
unhappiness	0
","	0
as	0
indicated	0
by	0
AMHS	0
scores	0
","	0
was	0
not	0
associated	0
with	0
arthritis	3
but	0
was	0
associated	0
with	0
sexual	3
dysfunction	4
","	0
sexual	0
dissatisfaction	0
and	0
being	0
female	0
.	0
Does	0
paracetamol	1
cause	0
urothelial	3
cancer	4
or	0
renal	3
papillary	4
necrosis	4
?	0
The	0
risk	0
of	0
developing	0
renal	3
papillary	4
necrosis	4
or	0
cancer	3
of	4
the	4
renal	4
pelvis	4
","	4
ureter	4
or	4
bladder	4
associated	0
with	0
consumption	0
of	0
either	0
phenacetin	1
or	0
paracetamol	1
was	0
calculated	0
from	0
data	0
acquired	0
by	0
questionnaire	0
from	0
381	0
cases	0
and	0
808	0
controls	0
.	0
The	0
risk	0
of	0
renal	3
papillary	4
necrosis	4
was	0
increased	0
nearly	0
20	0
-	0
fold	0
by	0
consumption	0
of	0
phenacetin	1
","	0
which	0
also	0
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the	0
risk	0
for	0
cancer	3
of	4
the	4
renal	4
pelvis	4
and	4
bladder	4
but	0
not	0
for	0
ureteric	3
cancer	4
.	0
By	0
contrast	0
","	0
we	0
were	0
unable	0
to	0
substantiate	0
an	0
increased	0
risk	0
from	0
paracetamol	1
consumption	0
for	0
renal	3
papillary	4
necrosis	4
or	0
any	0
of	0
these	0
cancers	3
although	0
there	0
was	0
a	0
suggestion	0
of	0
an	0
association	0
with	0
cancer	3
of	4
the	4
ureter	4
.	0
Dapsone	1
-	0
associated	0
Heinz	0
body	0
hemolytic	3
anemia	4
in	0
a	0
Cambodian	0
woman	0
with	0
hemoglobin	0
E	0
trait	0
.	0
A	0
Cambodian	0
woman	0
with	0
hemoglobin	0
E	0
trait	0
(	0
AE	0
)	0
and	0
leprosy	3
developed	0
a	0
Heinz	0
body	0
hemolytic	3
anemia	4
while	0
taking	0
a	0
dose	0
of	0
dapsone	1
(	0
50	0
mg	0
/	0
day	0
)	0
not	0
usually	0
associated	0
with	0
clinical	0
hemolysis	3
.	0
Her	0
red	0
blood	0
cells	0
(	0
RBCs	0
)	0
had	0
increased	0
incubated	0
Heinz	0
body	0
formation	0
","	0
decreased	0
reduced	0
glutathione	1
(	0
GSH	1
)	0
","	0
and	0
decreased	0
GSH	1
stability	0
.	0
The	0
pentose	1
phosphate	2
shunt	0
activity	0
of	0
the	0
dapsone	1
-	0
exposed	0
AE	0
RBCs	0
was	0
increased	0
compared	0
to	0
normal	0
RBCs	0
.	0
Although	0
the	0
AE	0
RBCs	0
from	0
an	0
individual	0
not	0
taking	0
dapsone	1
had	0
increased	0
incubated	0
Heinz	0
body	0
formation	0
","	0
the	0
GSH	1
content	0
and	0
GSH	1
stability	0
were	0
normal	0
.	0
The	0
pentose	1
phosphate	2
shunt	0
activity	0
of	0
the	0
non	0
-	0
dapsone	1
-	0
exposed	0
AE	0
RBCs	0
was	0
decreased	0
compared	0
to	0
normal	0
RBCs	0
.	0
Thus	0
","	0
AE	0
RBCs	0
appear	0
to	0
have	0
an	0
increased	0
sensitivity	0
to	0
oxidant	0
stress	0
both	0
in	0
vitro	0
and	0
in	0
vivo	0
","	0
since	0
dapsone	1
does	0
not	0
cause	0
hemolytic	3
anemia	4
at	0
this	0
dose	0
in	0
hematologically	0
normal	0
individuals	0
.	0
Given	0
the	0
influx	0
of	0
Southeast	0
Asians	0
into	0
the	0
United	0
States	0
","	0
oxidant	0
medications	0
should	0
be	0
used	0
with	0
caution	0
","	0
especially	0
if	0
an	0
infection	3
is	0
present	0
","	0
in	0
individuals	0
of	0
ethnic	0
backgrounds	0
that	0
have	0
an	0
increased	0
prevalence	0
of	0
hemoglobin	0
E	0
.	0
Severe	0
complications	0
of	0
antianginal	0
drug	0
therapy	0
in	0
a	0
patient	0
identified	0
as	0
a	0
poor	0
metabolizer	0
of	0
metoprolol	1
","	0
propafenone	1
","	0
diltiazem	1
","	0
and	0
sparteine	1
.	0
A	0
47	0
-	0
year	0
-	0
old	0
patient	0
suffering	0
from	0
coronary	3
artery	4
disease	4
was	0
admitted	0
to	0
the	0
CCU	0
in	0
shock	3
with	0
III	0
.	0
AV	3
block	4
","	0
severe	0
hypotension	3
","	0
and	0
impairment	3
of	4
ventricular	4
function	4
.	0
0ne	0
week	0
prior	0
to	0
admission	0
a	0
therapy	0
with	0
standard	0
doses	0
of	0
metoprolol	1
(	0
100	0
mg	0
t	0
.	0
i	0
.	0
d	0
.	0
and	0
then	0
100	0
mg	0
b	0
.	0
i	0
.	0
d	0
.	0
)	0
had	0
been	0
initiated	0
.	0
Two	0
days	0
before	0
admission	0
diltiazem	1
(	0
60	0
mg	0
b	0
.	0
i	0
.	0
d	0
.	0
)	0
was	0
prescribed	0
in	0
addition	0
.	0
Analyses	0
of	0
a	0
blood	0
sample	0
revealed	0
unusually	0
high	0
plasma	0
concentrations	0
of	0
metoprolol	1
(	0
greater	0
than	0
3000	0
ng	0
/	0
ml	0
)	0
and	0
diltiazem	1
(	0
526	0
ng	0
/	0
ml	0
)	0
.	0
The	0
patient	0
recovered	0
within	0
1	0
week	0
following	0
discontinuation	0
of	0
antianginal	0
therapy	0
.	0
Three	0
months	0
later	0
the	0
patient	0
was	0
exposed	0
to	0
a	0
single	0
dose	0
of	0
metoprolol	1
","	0
diltiazem	1
","	0
propafenone	1
(	0
since	0
he	0
had	0
received	0
this	0
drug	0
in	0
the	0
past	0
)	0
","	0
and	0
sparteine	1
(	0
as	0
a	0
probe	0
for	0
the	0
debrisoquine	1
/	0
sparteine	1
type	0
polymorphism	0
of	0
oxidative	0
drug	0
metabolism	0
)	0
.	0
It	0
was	0
found	0
that	0
he	0
was	0
a	0
poor	0
metabolizer	0
of	0
all	0
four	0
drugs	0
","	0
indicating	0
that	0
their	0
metabolism	0
is	0
under	0
the	0
same	0
genetic	0
control	0
.	0
Therefore	0
","	0
patients	0
belonging	0
to	0
the	0
poor	0
-	0
metabolizer	0
phenotype	0
of	0
sparteine	1
/	0
debrisoquine	1
polymorphism	0
in	0
drug	0
metabolism	0
","	0
which	0
constitutes	0
6	0
.	0
4	0
%	0
of	0
the	0
German	0
population	0
","	0
may	0
experience	0
adverse	3
drug	4
reactions	4
when	0
treated	0
with	0
standard	0
doses	0
of	0
one	0
of	0
these	0
drugs	0
alone	0
.	0
Moreover	0
","	0
the	0
coadministration	0
of	0
these	0
frequently	0
used	0
drugs	0
is	0
expected	0
to	0
be	0
especially	0
harmful	0
in	0
this	0
subgroup	0
of	0
patients	0
.	0
Clinical	0
experiences	0
in	0
an	0
open	0
and	0
a	0
double	0
-	0
blind	0
trial	0
.	0
A	0
total	0
of	0
sixty	0
patients	0
were	0
trated	0
with	0
bromperidol	1
first	0
in	0
open	0
conditions	0
(	0
20	0
patients	0
)	0
","	0
then	0
on	0
a	0
double	0
blind	0
basis	0
(	0
40	0
patients	0
)	0
with	0
haloperidol	1
as	0
the	0
reference	0
substance	0
.	0
The	0
open	0
study	0
lasted	0
for	0
four	0
weeks	0
;	0
the	0
drug	0
was	0
administrated	0
in	0
the	0
form	0
of	0
1	0
mg	0
tablets	0
.	0
The	0
daily	0
dose	0
(	0
initial	0
dose	0
:	0
1	0
mg	0
;	0
mean	0
dose	0
at	0
the	0
end	0
of	0
the	0
trial	0
:	0
4	0
.	0
47	0
mg	0
)	0
was	0
always	0
administered	0
in	0
one	0
single	0
dose	0
.	0
Nineteen	0
patients	0
finished	0
the	0
trial	0
","	0
and	0
in	0
18	0
cases	0
the	0
therapeutic	0
result	0
was	0
considered	0
very	0
good	0
to	0
good	0
.	0
These	0
results	0
were	0
confirmed	0
by	0
statistical	0
analysis	0
.	0
Nine	0
patients	0
exhibited	0
mild	0
to	0
moderate	0
extrapyramidal	3
concomitant	4
symptoms	4
;	0
no	0
other	0
side	0
effects	0
were	0
observed	0
.	0
The	0
results	0
of	0
detailed	0
laboratory	0
tests	0
and	0
evaluations	0
of	0
various	0
quantitative	0
and	0
qualitative	0
tolerability	0
parameters	0
were	0
not	0
indicative	0
of	0
toxic	0
effects	0
.	0
In	0
the	0
double	0
blind	0
study	0
with	0
haloperidol	1
","	0
both	0
substances	0
were	0
found	0
to	0
be	0
highly	0
effective	0
in	0
the	0
treatment	0
of	0
psychotic	3
syndromes	4
belonging	4
predominantly	4
to	4
the	4
schizophrenia	4
group	4
.	0
Certain	0
clues	0
","	0
including	0
the	0
onset	0
of	0
action	0
","	0
seem	0
to	0
be	0
indicative	0
of	0
the	0
superiority	0
of	0
bromperidol	1
.	0
No	0
differences	0
were	0
observed	0
with	0
respect	0
to	0
side	0
effects	0
and	0
general	0
tolerability	0
.	0
Prolonged	0
cholestasis	3
after	0
troleandomycin	1
-	0
induced	0
acute	0
hepatitis	3
.	0
We	0
report	0
the	0
case	0
of	0
a	0
patient	0
in	0
whom	0
troleandomycin	1
-	0
induced	0
hepatitis	3
was	0
followed	0
by	0
prolonged	0
anicteric	0
cholestasis	3
.	0
Jaundice	3
occurred	0
after	0
administration	0
of	0
troleandomycin	1
for	0
7	0
days	0
and	0
was	0
associated	0
with	0
hypereosinophilia	3
.	0
Jaundice	3
disappeared	0
within	0
3	0
months	0
but	0
was	0
followed	0
by	0
prolonged	0
anicteric	0
cholestasis	3
marked	0
by	0
pruritus	3
and	0
high	0
levels	0
of	0
alkaline	0
phosphatase	0
and	0
gammaglutamyltransferase	0
activities	0
.	0
Finally	0
","	0
pruritus	3
disappeared	0
within	0
19	0
months	0
","	0
and	0
liver	0
tests	0
returned	0
to	0
normal	0
27	0
months	0
after	0
the	0
onset	0
of	0
hepatitis	3
.	0
This	0
observation	0
demonstrates	0
that	0
prolonged	0
cholestasis	3
can	0
follow	0
troleandomycin	1
-	0
induced	0
acute	0
hepatitis	3
.	0
Serial	0
studies	0
of	0
auditory	3
neurotoxicity	4
in	0
patients	0
receiving	0
deferoxamine	1
therapy	0
.	0
Visual	3
and	4
auditory	4
neurotoxicity	4
was	0
previously	0
documented	0
in	0
42	0
of	0
89	0
patients	0
with	0
transfusion	0
-	0
dependent	0
anemia	3
who	0
were	0
receiving	0
iron	1
chelation	0
therapy	0
with	0
daily	0
subcutaneous	0
deferoxamine	1
.	0
Twenty	0
-	0
two	0
patients	0
in	0
the	0
affected	0
group	0
had	0
abnormal	3
audiograms	4
with	4
deficits	4
mostly	4
in	4
the	4
high	4
frequency	4
range	4
of	4
4	4
","	4
0	4
to	4
8	4
","	4
0	4
Hz	4
and	0
in	0
the	0
hearing	0
threshold	0
levels	0
of	0
30	0
to	0
100	0
decibels	0
.	0
When	0
deferoxamine	1
therapy	0
was	0
discontinued	0
and	0
serial	0
studies	0
were	0
performed	0
","	0
audiograms	0
in	0
seven	0
cases	0
reverted	0
to	0
normal	0
or	0
near	0
normal	0
within	0
two	0
to	0
three	0
weeks	0
","	0
and	0
nine	0
of	0
13	0
patients	0
with	0
symptoms	0
became	0
asymptomatic	0
.	0
Audiograms	0
from	0
15	0
patients	0
remained	0
abnormal	0
and	0
four	0
patients	0
required	0
hearing	0
aids	0
because	0
of	0
permanent	3
disability	4
.	0
Since	0
18	0
of	0
the	0
22	0
patients	0
were	0
initially	0
receiving	0
deferoxamine	1
doses	0
in	0
excess	0
of	0
the	0
commonly	0
recommended	0
50	0
mg	0
/	0
kg	0
per	0
dose	0
","	0
therapy	0
was	0
restarted	0
with	0
lower	0
doses	0
","	0
usually	0
50	0
mg	0
/	0
kg	0
per	0
dose	0
or	0
less	0
depending	0
on	0
the	0
degree	0
of	0
auditory	3
abnormality	4
","	0
and	0
with	0
the	0
exception	0
of	0
two	0
cases	0
no	0
further	0
toxicity	3
was	0
demonstrated	0
.	0
Auditory	0
deterioration	0
and	0
improvement	0
","	0
demonstrated	0
serially	0
in	0
individual	0
patients	0
receiving	0
and	0
not	0
receiving	0
deferoxamine	1
","	0
respectively	0
","	0
provided	0
convincing	0
evidence	0
for	0
a	0
cause	0
-	0
and	0
-	0
effect	0
relation	0
between	0
deferoxamine	1
administration	0
and	0
ototoxicity	3
.	0
Based	0
on	0
these	0
data	0
","	0
a	0
plan	0
of	0
management	0
was	0
developed	0
that	0
allows	0
effective	0
yet	0
safe	0
administration	0
of	0
deferoxamine	1
.	0
A	0
dose	0
of	0
50	0
mg	0
/	0
kg	0
is	0
recommended	0
in	0
those	0
without	0
audiogram	0
abnormalities	0
.	0
With	0
mild	0
toxicity	3
","	0
a	0
reduction	0
to	0
30	0
or	0
40	0
mg	0
/	0
kg	0
per	0
dose	0
should	0
result	0
in	0
a	0
reversal	0
of	0
the	0
abnormal	0
results	0
to	0
normal	0
within	0
four	0
weeks	0
.	0
Moderate	0
abnormalities	0
require	0
a	0
reduction	0
of	0
deferoxamine	1
to	0
25	0
mg	0
/	0
kg	0
per	0
dose	0
with	0
careful	0
monitoring	0
.	0
In	0
those	0
with	0
symptoms	0
of	0
hearing	3
loss	4
","	0
the	0
drug	0
should	0
be	0
stopped	0
for	0
four	0
weeks	0
","	0
and	0
when	0
the	0
audiogram	0
is	0
stable	0
or	0
improved	0
","	0
therapy	0
should	0
be	0
restarted	0
at	0
10	0
to	0
25	0
mg	0
/	0
kg	0
per	0
dose	0
.	0
Serial	0
audiograms	0
should	0
be	0
performed	0
every	0
six	0
months	0
in	0
those	0
without	0
problems	0
and	0
more	0
frequently	0
in	0
young	0
patients	0
with	0
normal	0
serum	0
ferritin	0
values	0
and	0
in	0
those	0
with	0
auditory	3
dysfunction	4
.	0
Lidocaine	1
-	0
induced	0
cardiac	3
asystole	4
.	0
Intravenous	0
administration	0
of	0
a	0
single	0
50	0
-	0
mg	0
bolus	0
of	0
lidocaine	1
in	0
a	0
67	0
-	0
year	0
-	0
old	0
man	0
resulted	0
in	0
profound	0
depression	3
of	0
the	0
activity	0
of	0
the	0
sinoatrial	0
and	0
atrioventricular	0
nodal	0
pacemakers	0
.	0
The	0
patient	0
had	0
no	0
apparent	0
associated	0
conditions	0
which	0
might	0
have	0
predisposed	0
him	0
to	0
the	0
development	0
of	0
bradyarrhythmias	3
;	0
and	0
","	0
thus	0
","	0
this	0
probably	0
represented	0
a	0
TRUE	0
idiosyncrasy	0
to	0
lidocaine	1
.	0
Flurbiprofen	1
in	0
the	0
treatment	0
of	0
juvenile	3
rheumatoid	4
arthritis	4
.	0
Thirty	0
-	0
four	0
patients	0
with	0
juvenile	3
rheumatoid	4
arthritis	4
","	0
who	0
were	0
treated	0
with	0
flurbiprofen	1
at	0
a	0
maximum	0
dose	0
of	0
4	0
mg	0
/	0
kg	0
/	0
day	0
","	0
had	0
statistically	0
significant	0
decreases	0
from	0
baseline	0
in	0
6	0
arthritis	3
indices	0
after	0
12	0
weeks	0
of	0
treatment	0
.	0
Improvements	0
were	0
seen	0
in	0
the	0
number	0
of	0
tender	3
joints	4
","	0
the	0
severity	0
of	0
swelling	3
and	0
tenderness	3
","	0
the	0
time	0
of	0
walk	0
50	0
feet	0
","	0
the	0
duration	0
of	0
morning	3
stiffness	4
and	0
the	0
circumference	0
of	0
the	0
left	0
knee	0
.	0
The	0
most	0
frequently	0
observed	0
side	0
effect	0
was	0
fecal	3
occult	4
blood	4
(	0
25	0
%	0
of	0
patients	0
)	0
;	0
however	0
","	0
there	0
was	0
no	0
other	0
evidence	0
of	0
gastrointestinal	3
(	4
GI	4
)	4
bleeding	4
in	0
these	0
patients	0
.	0
0ne	0
patient	0
was	0
prematurely	0
discontinued	0
from	0
the	0
study	0
for	0
severe	0
headache	3
and	0
abdominal	3
pain	4
.	0
Most	0
side	0
effects	0
were	0
mild	0
and	0
related	0
to	0
the	0
GI	0
tract	0
.	0
Hyperkalemia	3
associated	0
with	0
sulindac	1
therapy	0
.	0
Hyperkalemia	3
has	0
recently	0
been	0
recognized	0
as	0
a	0
complication	0
of	0
nonsteroidal	0
antiinflammatory	0
agents	0
(	0
NSAID	0
)	0
such	0
as	0
indomethacin	1
.	0
Several	0
recent	0
studies	0
have	0
stressed	0
the	0
renal	0
sparing	0
features	0
of	0
sulindac	1
","	0
owing	0
to	0
its	0
lack	0
of	0
interference	0
with	0
renal	0
prostacyclin	1
synthesis	0
.	0
We	0
describe	0
4	0
patients	0
in	0
whom	0
hyperkalemia	3
ranging	0
from	0
6	0
.	0
1	0
to	0
6	0
.	0
9	0
mEq	0
/	0
l	0
developed	0
within	0
3	0
to	0
8	0
days	0
of	0
sulindac	1
administration	0
.	0
In	0
all	0
of	0
them	0
normal	0
serum	0
potassium	1
levels	0
reached	0
within	0
2	0
to	0
4	0
days	0
of	0
stopping	0
sulindac	1
.	0
As	0
no	0
other	0
medications	0
known	0
to	0
effect	0
serum	0
potassium	1
had	0
been	0
given	0
concomitantly	0
","	0
this	0
course	0
of	0
events	0
is	0
suggestive	0
of	0
a	0
cause	0
-	0
and	0
-	0
effect	0
relationship	0
between	0
sulindac	1
and	0
hyperkalemia	3
.	0
These	0
observations	0
indicate	0
that	0
initial	0
hopes	0
that	0
sulindac	1
may	0
not	0
be	0
associated	0
with	0
the	0
adverse	0
renal	0
effects	0
of	0
other	0
NSAID	0
are	0
probably	0
not	0
justified	0
.	0
Drug	0
-	0
induced	0
arterial	0
spasm	3
relieved	0
by	0
lidocaine	1
.	0
Case	0
report	0
.	0
Following	0
major	0
intracranial	0
surgery	0
in	0
a	0
35	0
-	0
year	0
-	0
old	0
man	0
","	0
sodium	1
pentothal	2
was	0
intravenously	0
infused	0
to	0
minimize	0
cerebral	3
ischaemia	4
.	0
Intense	0
vasospasm	3
with	0
threatened	0
gangrene	3
arose	0
in	0
the	0
arm	0
used	0
for	0
the	0
infusion	0
.	0
Since	0
the	0
cranial	0
condition	0
precluded	0
use	0
of	0
more	0
usual	0
methods	0
","	0
lidocaine	1
was	0
given	0
intra	0
-	0
arterially	0
","	0
with	0
careful	0
cardiovascular	0
monitoring	0
","	0
to	0
counteract	0
the	0
vasospasm	3
.	0
The	0
treatment	0
was	0
rapidly	0
successful	0
.	0
Regional	0
localization	0
of	0
the	0
antagonism	0
of	0
amphetamine	1
-	0
induced	0
hyperactivity	3
by	0
intracerebral	0
calcitonin	1
injections	0
.	0
Calcitonin	1
receptors	0
are	0
found	0
in	0
the	0
brain	0
","	0
and	0
intracerebral	0
infusions	0
of	0
calcitonin	1
can	0
produce	0
behavioral	0
effects	0
.	0
Among	0
these	0
behavioral	0
effects	0
are	0
decreases	0
in	0
food	0
intake	0
and	0
decreases	0
in	0
amphetamine	1
-	0
induced	0
locomotor	0
activity	0
.	0
In	0
previous	0
experiments	0
we	0
found	0
that	0
decreases	0
in	0
food	0
intake	0
were	0
induced	0
by	0
local	0
administration	0
of	0
calcitonin	1
into	0
several	0
hypothalamic	0
sites	0
and	0
into	0
the	0
nucleus	0
accumbens	0
.	0
In	0
the	0
present	0
experiment	0
calcitonin	1
decreased	0
locomotor	0
activity	0
when	0
locally	0
injected	0
into	0
the	0
same	0
sites	0
where	0
it	0
decreases	0
food	0
intake	0
.	0
The	0
areas	0
where	0
calcitonin	1
is	0
most	0
effective	0
in	0
decreasing	0
locomotor	0
activity	0
are	0
located	0
in	0
the	0
hypothalamus	0
and	0
nucleus	0
accumbens	0
","	0
suggesting	0
that	0
these	0
areas	0
are	0
the	0
major	0
sites	0
of	0
action	0
of	0
calcitonin	1
in	0
inhibiting	0
amphetamine	1
-	0
induced	0
locomotor	0
activity	0
.	0
The	0
hematologic	0
effects	0
of	0
cefonicid	1
and	0
cefazedone	1
in	0
the	0
dog	0
:	0
a	0
potential	0
model	0
of	0
cephalosporin	1
hematotoxicity	3
in	0
man	0
.	0
Cephalosporin	1
antibiotics	0
cause	0
a	0
variety	0
of	0
hematologic	3
disturbances	4
in	0
man	0
","	0
the	0
pathogeneses	0
and	0
hematopathology	0
of	0
which	0
remain	0
poorly	0
characterized	0
.	0
There	0
is	0
a	0
need	0
for	0
a	0
well	0
-	0
defined	0
animal	0
model	0
in	0
which	0
these	0
blood	3
dyscrasias	4
can	0
be	0
studied	0
.	0
In	0
four	0
subacute	0
toxicity	3
studies	0
","	0
the	0
intravenous	0
administration	0
of	0
cefonicid	1
or	0
cefazedone	1
to	0
beagle	0
dogs	0
caused	0
a	0
dose	0
-	0
dependent	0
incidence	0
of	0
anemia	3
","	0
neutropenia	3
","	0
and	0
thrombocytopenia	3
after	0
1	0
-	0
3	0
months	0
of	0
treatment	0
.	0
A	0
nonregenerative	0
anemia	3
was	0
the	0
most	0
compromising	0
of	0
the	0
cytopenias	3
and	0
occurred	0
in	0
approximately	0
50	0
%	0
of	0
dogs	0
receiving	0
400	0
-	0
500	0
mg	0
/	0
kg	0
cefonicid	1
or	0
540	0
-	0
840	0
mg	0
/	0
kg	0
cefazedone	1
.	0
All	0
three	0
cytopenias	3
were	0
completely	0
reversible	0
following	0
cessation	0
of	0
treatment	0
;	0
the	0
time	0
required	0
for	0
recovery	0
of	0
the	0
erythron	0
(	0
approximately	0
1	0
month	0
)	0
was	0
considerably	0
longer	0
than	0
that	0
of	0
the	0
granulocytes	0
and	0
platelets	0
(	0
hours	0
to	0
a	0
few	0
days	0
)	0
.	0
Upon	0
rechallenge	0
with	0
either	0
cephalosporin	1
","	0
the	0
hematologic	3
syndrome	4
was	0
reproduced	0
in	0
most	0
dogs	0
tested	0
;	0
cefonicid	1
(	0
but	0
not	0
cefazedone	1
)	0
-	0
treated	0
dogs	0
showed	0
a	0
substantially	0
reduced	0
induction	0
period	0
(	0
15	0
+	0
/	0
-	0
5	0
days	0
)	0
compared	0
to	0
that	0
of	0
the	0
first	0
exposure	0
to	0
the	0
drug	0
(	0
61	0
+	0
/	0
-	0
24	0
days	0
)	0
.	0
This	0
observation	0
","	0
along	0
with	0
the	0
rapid	0
rate	0
of	0
decline	0
in	0
red	0
cell	0
mass	0
parameters	0
of	0
affected	0
dogs	0
","	0
suggests	0
that	0
a	0
hemolytic	3
component	0
complicated	0
the	0
red	0
cell	0
production	0
problem	0
and	0
that	0
multiple	0
toxicologic	0
mechanisms	0
contributed	0
to	0
the	0
cytopenia	3
.	0
We	0
conclude	0
that	0
the	0
administration	0
of	0
high	0
doses	0
of	0
cefonicid	1
or	0
cefazedone	1
to	0
dogs	0
can	0
induce	0
hematotoxicity	3
similar	0
to	0
the	0
cephalosporin	1
-	0
induced	0
blood	3
dyscrasias	4
described	0
in	0
man	0
and	0
thus	0
provides	0
a	0
useful	0
model	0
for	0
studying	0
the	0
mechanisms	0
of	0
these	0
disorders	0
.	0
Cerebral	0
blood	0
flow	0
and	0
metabolism	0
during	0
isoflurane	1
-	0
induced	0
hypotension	3
in	0
patients	0
subjected	0
to	0
surgery	0
for	0
cerebral	3
aneurysms	4
.	0
Cerebral	0
blood	0
flow	0
and	0
cerebral	0
metabolic	0
rate	0
for	0
oxygen	1
were	0
measured	0
during	0
isoflurane	1
-	0
induced	0
hypotension	3
in	0
10	0
patients	0
subjected	0
to	0
craniotomy	0
for	0
clipping	0
of	0
a	0
cerebral	3
aneurysm	4
.	0
Flow	0
and	0
metabolism	0
were	0
measured	0
5	0
-	0
13	0
days	0
after	0
the	0
subarachnoid	3
haemorrhage	4
by	0
a	0
modification	0
of	0
the	0
classical	0
Kety	0
-	0
Schmidt	0
technique	0
using	0
xenon	1
-	0
133	0
i	0
.	0
v	0
.	0
Anaesthesia	0
was	0
maintained	0
with	0
an	0
inspired	0
isoflurane	1
concentration	0
of	0
0	0
.	0
75	0
%	0
(	0
plus	0
67	0
%	0
nitrous	1
oxide	2
in	0
oxygen	1
)	0
","	0
during	0
which	0
CBF	0
and	0
CMR02	0
were	0
34	0
.	0
3	0
+	0
/	0
-	0
2	0
.	0
1	0
ml	0
/	0
100	0
g	0
min	0
-	0
1	0
and	0
2	0
.	0
32	0
+	0
/	0
-	0
0	0
.	0
16	0
ml	0
/	0
100	0
g	0
min	0
-	0
1	0
at	0
PaC02	0
4	0
.	0
1	0
+	0
/	0
-	0
0	0
.	0
1	0
kPa	0
(	0
mean	0
+	0
/	0
-	0
SEM	0
)	0
.	0
Controlled	0
hypotension	3
to	0
an	0
average	0
MAP	0
of	0
50	0
-	0
55	0
mm	0
Hg	1
was	0
induced	0
by	0
increasing	0
the	0
dose	0
of	0
isoflurane	1
","	0
and	0
maintained	0
at	0
an	0
inspired	0
concentration	0
of	0
2	0
.	0
2	0
+	0
/	0
-	0
0	0
.	0
2	0
%	0
.	0
This	0
resulted	0
in	0
a	0
significant	0
decrease	0
in	0
CMR02	0
(	0
to	0
1	0
.	0
73	0
+	0
/	0
-	0
0	0
.	0
16	0
ml	0
/	0
100	0
g	0
min	0
-	0
1	0
)	0
","	0
while	0
CBF	0
was	0
unchanged	0
.	0
After	0
the	0
clipping	0
of	0
the	0
aneurysm	3
the	0
isoflurane	1
concentration	0
was	0
reduced	0
to	0
0	0
.	0
75	0
%	0
.	0
There	0
was	0
a	0
significant	0
increase	0
in	0
CBF	0
","	0
although	0
CMR02	0
was	0
unchanged	0
","	0
compared	0
with	0
pre	0
-	0
hypotensive	3
values	0
.	0
These	0
changes	0
might	0
offer	0
protection	0
to	0
brain	0
tissue	0
during	0
periods	0
of	0
induced	0
hypotension	3
.	0
Triazolam	1
-	0
induced	0
brief	0
episodes	0
of	0
secondary	0
mania	3
in	0
a	0
depressed	3
patient	0
.	0
Large	0
doses	0
of	0
triazolam	1
repeatedly	0
induced	0
brief	0
episodes	0
of	0
mania	3
in	0
a	0
depressed	3
elderly	0
woman	0
.	0
Features	0
of	0
organic	3
mental	4
disorder	4
(	0
delirium	3
)	0
were	0
not	0
present	0
.	0
Manic	3
excitement	0
was	0
coincident	0
with	0
the	0
duration	0
of	0
action	0
of	0
triazolam	1
.	0
The	0
possible	0
contribution	0
of	0
the	0
triazolo	1
group	0
to	0
changes	0
in	0
affective	0
status	0
is	0
discussed	0
.	0
The	0
correlation	0
between	0
neurotoxic	3
esterase	0
inhibition	0
and	0
mipafox	1
-	0
induced	0
neuropathic	3
damage	4
in	0
rats	0
.	0
The	0
correlation	0
between	0
neuropathic	3
damage	4
and	0
inhibition	0
of	0
neurotoxic	3
esterase	0
or	0
neuropathy	3
target	0
enzyme	0
(	0
NTE	0
)	0
was	0
examined	0
in	0
rats	0
acutely	0
exposed	0
to	0
Mipafox	1
(	0
N	1
","	2
N	2
'	2
-	2
diisopropylphosphorodiamidofluoridate	2
)	0
","	0
a	0
neurotoxic	3
organophosphate	1
.	0
Brain	0
and	0
spinal	0
cord	0
NTE	0
activities	0
were	0
measured	0
in	0
Long	0
-	0
Evans	0
male	0
rats	0
1	0
hr	0
post	0
-	0
exposure	0
to	0
various	0
dosages	0
of	0
Mipafox	1
(	0
ip	0
","	0
1	0
-	0
15	0
mg	0
/	0
kg	0
)	0
.	0
These	0
data	0
were	0
correlated	0
with	0
histologically	0
scored	0
cervical	0
cord	3
damage	4
in	0
a	0
separate	0
group	0
of	0
similarly	0
dosed	0
rats	0
sampled	0
14	0
-	0
21	0
days	0
post	0
-	0
exposure	0
.	0
Those	0
dosages	0
(	0
greater	0
than	0
or	0
equal	0
to	0
10	0
mg	0
/	0
kg	0
)	0
that	0
inhibited	0
mean	0
NTE	0
activity	0
in	0
the	0
spinal	0
cord	0
greater	0
than	0
or	0
equal	0
to	0
73	0
%	0
and	0
brain	0
greater	0
than	0
or	0
equal	0
to	0
67	0
%	0
of	0
control	0
values	0
produced	0
severe	0
(	0
greater	0
than	0
or	0
equal	0
to	0
3	0
)	0
cervical	0
cord	0
pathology	0
in	0
85	0
%	0
of	0
the	0
rats	0
.	0
In	0
contrast	0
","	0
dosages	0
of	0
Mipafox	1
(	0
less	0
than	0
or	0
equal	0
to	0
5	0
mg	0
/	0
kg	0
)	0
which	0
inhibited	0
mean	0
NTE	0
activity	0
in	0
spinal	0
cord	0
less	0
than	0
or	0
equal	0
to	0
61	0
%	0
and	0
brain	0
less	0
than	0
or	0
equal	0
to	0
60	0
%	0
produced	0
this	0
degree	0
of	0
cord	3
damage	4
in	0
only	0
9	0
%	0
of	0
the	0
animals	0
.	0
These	0
data	0
indicate	0
that	0
a	0
critical	0
percentage	0
of	0
NTE	0
inhibition	0
in	0
brain	0
and	0
spinal	0
cord	0
sampled	0
shortly	0
after	0
Mipafox	1
exposure	0
can	0
predict	0
neuropathic	3
damage	4
in	0
rats	0
several	0
weeks	0
later	0
.	0
Allergic	3
reaction	4
to	0
5	1
-	2
fluorouracil	2
infusion	0
.	0
An	0
allergic	3
reaction	4
consisting	0
of	0
angioneurotic	3
edema	4
secondary	0
to	0
continuous	0
infusion	0
5	1
-	2
fluorouracil	2
occurred	0
in	0
a	0
patient	0
with	0
recurrent	0
carcinoma	3
of	4
the	4
oral	4
cavity	4
","	0
cirrhosis	3
","	0
and	0
cisplatin	1
-	0
induced	0
impaired	3
renal	4
function	4
.	0
This	0
reaction	0
occurred	0
during	0
the	0
sixth	0
and	0
seventh	0
courses	0
of	0
infusional	0
chemotherapy	0
.	0
0ral	0
diphenhydramine	1
and	0
prednisone	1
were	0
ineffective	0
in	0
preventing	0
the	0
recurrence	0
of	0
the	0
allergic	3
reaction	4
.	0
Discontinuance	0
of	0
effective	0
chemotherapy	0
in	0
this	0
patient	0
during	0
partial	0
remission	0
resulted	0
in	0
fatal	0
disease	0
progression	0
.	0
Myasthenia	3
gravis	4
caused	0
by	0
penicillamine	1
and	0
chloroquine	1
therapy	0
for	0
rheumatoid	3
arthritis	4
.	0
We	0
have	0
described	0
a	0
unique	0
patient	0
who	0
had	0
reversible	0
and	0
dose	0
-	0
related	0
myasthenia	3
gravis	4
after	0
penicillamine	1
and	0
chloroquine	1
therapy	0
for	0
rheumatoid	3
arthritis	4
.	0
Although	0
acetylcholine	1
receptor	0
antibodies	0
were	0
not	0
detectable	0
","	0
the	0
time	0
course	0
was	0
consistent	0
with	0
an	0
autoimmune	0
process	0
.	0
0n	0
the	0
mechanisms	0
of	0
the	0
development	0
of	0
tolerance	0
to	0
the	0
muscular	3
rigidity	4
produced	0
by	0
morphine	1
in	0
rats	0
.	0
The	0
development	0
of	0
tolerance	0
to	0
the	0
muscular	3
rigidity	4
produced	0
by	0
morphine	1
was	0
studied	0
in	0
rats	0
.	0
Saline	0
-	0
pretreated	0
controls	0
given	0
a	0
test	0
dose	0
of	0
morphine	1
(	0
20	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
showed	0
a	0
pronounced	0
rigidity	3
recorded	0
as	0
tonic	0
activity	0
in	0
the	0
electromyogram	0
.	0
Rats	0
treated	0
for	0
11	0
days	0
with	0
morphine	1
and	0
withdrawn	0
for	0
36	0
-	0
40	0
h	0
showed	0
differences	0
in	0
the	0
development	0
of	0
tolerance	0
:	0
about	0
half	0
of	0
the	0
animals	0
showed	0
a	0
rigidity	3
after	0
the	0
test	0
dose	0
of	0
morphine	1
that	0
was	0
not	0
significantly	0
less	0
than	0
in	0
the	0
controls	0
and	0
were	0
akinetic	3
(	0
A	0
group	0
)	0
.	0
The	0
other	0
rats	0
showed	0
a	0
strong	0
decrease	0
in	0
the	0
rigidity	3
and	0
the	0
occurrence	0
of	0
stereotyped	0
(	0
S	0
)	0
licking	0
and	0
/	0
or	0
gnawing	0
in	0
presence	0
of	0
akinetic	3
or	0
hyperkinetic	3
(	0
K	0
)	0
behaviour	0
(	0
AS	0
/	0
KS	0
group	0
)	0
","	0
suggesting	0
signs	0
of	0
dopaminergic	0
activation	0
.	0
The	0
rigidity	3
was	0
considerably	0
decreased	0
in	0
both	0
groups	0
after	0
20	0
days	0
'	0
treatment	0
.	0
In	0
a	0
further	0
series	0
of	0
experiments	0
","	0
haloperidol	1
(	0
0	0
.	0
2	0
mg	0
/	0
kg	0
i	0
.	0
p	0
.	0
)	0
was	0
used	0
in	0
order	0
to	0
block	0
the	0
dopaminergic	0
activation	0
and	0
to	0
estimate	0
the	0
real	0
degree	0
of	0
the	0
tolerance	0
to	0
the	0
rigidity	3
without	0
any	0
dopaminergic	0
interference	0
.	0
Haloperidol	1
enhanced	0
the	0
rigidity	3
in	0
the	0
A	0
group	0
.	0
However	0
","	0
the	0
level	0
in	0
the	0
AS	0
/	0
KS	0
group	0
remained	0
considerably	0
lower	0
than	0
in	0
the	0
A	0
group	0
.	0
The	0
results	0
suggest	0
that	0
rigidity	3
","	0
which	0
is	0
assumed	0
to	0
be	0
due	0
to	0
an	0
action	0
of	0
morphine	1
in	0
the	0
striatum	0
","	0
can	0
be	0
antagonized	0
by	0
another	0
process	0
leading	0
to	0
dopaminergic	0
activation	0
in	0
the	0
striatum	0
.	0
Nevertheless	0
","	0
there	0
occurs	0
some	0
real	0
tolerance	0
to	0
this	0
effect	0
.	0
The	0
rapid	0
alternations	0
of	0
rigidity	3
and	0
the	0
signs	0
of	0
dopaminergic	0
activation	0
observed	0
in	0
the	0
animals	0
of	0
the	0
AS	0
/	0
KS	0
group	0
might	0
be	0
due	0
to	0
rapid	0
shifts	0
in	0
the	0
predominance	0
of	0
various	0
DA	0
-	0
innervated	0
structures	0
.	0
A	0
case	0
of	0
massive	0
rhabdomyolysis	3
following	0
molindone	1
administration	0
.	0
Rhabdomyolysis	3
is	0
a	0
potentially	0
lethal	0
syndrome	0
that	0
psychiatric	3
patients	0
seem	0
predisposed	0
to	0
develop	0
.	0
The	0
clinical	0
signs	0
and	0
symptoms	0
","	0
typical	0
laboratory	0
features	0
","	0
and	0
complications	0
of	0
rhabdomyolysis	3
are	0
presented	0
.	0
The	0
case	0
of	0
a	0
schizophrenic	3
patient	0
is	0
reported	0
to	0
illustrate	0
massive	0
rhabdomyolysis	3
and	0
subsequent	0
acute	3
renal	4
failure	4
following	0
molindone	1
administration	0
.	0
Physicians	0
who	0
prescribe	0
molindone	1
should	0
be	0
aware	0
of	0
this	0
reaction	0
.	0
Compression	3
neuropathy	4
of	4
the	4
radial	4
nerve	4
due	0
to	0
pentazocine	1
-	0
induced	0
fibrous	3
myopathy	4
.	0
Fibrous	3
myopathy	4
is	0
a	0
common	0
","	0
well	0
-	0
known	0
side	0
effect	0
of	0
repeated	0
pentazocine	1
injection	0
.	0
However	0
","	0
compression	3
neuropathy	4
due	0
to	0
fibrotic	0
muscle	0
affected	0
by	0
pentazocine	1
-	0
induced	0
myopathy	3
has	0
not	0
previously	0
been	0
reported	0
.	0
In	0
a	0
37	0
-	0
year	0
-	0
old	0
woman	0
with	0
documented	0
pentazocine	1
-	0
induced	0
fibrous	3
myopathy	4
of	0
triceps	0
and	0
deltoid	0
muscles	0
bilaterally	0
and	0
a	0
three	0
-	0
week	0
history	0
of	0
right	0
wrist	0
drop	0
","	0
electrodiagnostic	0
examination	0
showed	0
a	0
severe	0
but	0
partial	0
lesion	0
of	0
the	0
right	0
radial	0
nerve	0
distal	0
to	0
the	0
branches	0
to	0
the	0
triceps	0
","	0
in	0
addition	0
to	0
the	0
fibrous	3
myopathy	4
.	0
Surgery	0
revealed	0
the	0
right	0
radial	0
nerve	0
to	0
be	0
severely	0
compressed	0
by	0
the	0
densely	0
fibrotic	0
lateral	0
head	0
of	0
the	0
triceps	0
.	0
Decompression	0
and	0
neurolysis	0
were	0
performed	0
with	0
good	0
subsequent	0
recovery	0
of	0
function	0
.	0
Recurrent	0
reversible	0
acute	3
renal	4
failure	4
from	0
amphotericin	1
.	0
A	0
patient	0
with	0
cryptogenic	0
cirrhosis	3
and	0
disseminated	0
sporotrichosis	3
developed	0
acute	3
renal	4
failure	4
immediately	0
following	0
the	0
administration	0
of	0
amphotericin	1
B	2
on	0
four	0
separate	0
occasions	0
.	0
The	0
abruptness	0
of	0
the	0
renal	3
failure	4
and	0
its	0
reversibility	0
within	0
days	0
suggests	0
that	0
there	0
was	0
a	0
functional	0
component	0
to	0
the	0
renal	3
dysfunction	4
.	0
We	0
propose	0
that	0
amphotericin	1
","	0
in	0
the	0
setting	0
of	0
reduced	0
effective	0
arterial	0
volume	0
","	0
may	0
activate	0
tubuloglomerular	0
feedback	0
","	0
thereby	0
contributing	0
to	0
acute	3
renal	4
failure	4
.	0
Cerebral	3
infarction	4
with	0
a	0
single	0
oral	0
dose	0
of	0
phenylpropanolamine	1
.	0
Phenylpropanolamine	1
(	0
PPA	1
)	0
","	0
a	0
synthetic	0
sympathomimetic	0
that	0
is	0
structurally	0
similar	0
to	0
amphetamine	1
","	0
is	0
available	0
over	0
the	0
counter	0
in	0
anorectics	0
","	0
nasal	0
congestants	0
","	0
and	0
cold	0
preparations	0
.	0
Its	0
prolonged	0
use	0
or	0
overuse	0
has	0
been	0
associated	0
with	0
seizures	3
","	0
intracerebral	3
hemorrhage	4
","	0
neuropsychiatric	3
symptoms	4
","	0
and	0
nonhemorrhagic	0
cerebral	3
infarction	4
.	0
We	0
report	0
the	0
case	0
of	0
a	0
young	0
woman	0
who	0
suffered	0
a	0
cerebral	3
infarction	4
after	0
taking	0
a	0
single	0
oral	0
dose	0
of	0
PPA	1
.	0
Remission	0
induction	0
of	0
meningeal	3
leukemia	4
with	0
high	0
-	0
dose	0
intravenous	0
methotrexate	1
.	0
Twenty	0
children	0
with	0
acute	3
lymphoblastic	4
leukemia	4
who	0
developed	0
meningeal	3
disease	4
were	0
treated	0
with	0
a	0
high	0
-	0
dose	0
intravenous	0
methotrexate	1
regimen	0
that	0
was	0
designed	0
to	0
achieve	0
and	0
maintain	0
CSF	0
methotrexate	1
concentrations	0
of	0
10	0
(	0
-	0
5	0
)	0
mol	0
/	0
L	0
without	0
the	0
need	0
for	0
concomitant	0
intrathecal	0
dosing	0
.	0
The	0
methotrexate	1
was	0
administered	0
as	0
a	0
loading	0
dose	0
of	0
6	0
","	0
0	0
mg	0
/	0
m2	0
for	0
a	0
period	0
of	0
one	0
hour	0
followed	0
by	0
an	0
infusion	0
of	0
1	0
","	0
200	0
mg	0
/	0
m2	0
/	0
h	0
for	0
23	0
hours	0
.	0
Leucovorin	1
rescue	0
was	0
initiated	0
12	0
hours	0
after	0
the	0
end	0
of	0
the	0
infusion	0
with	0
a	0
loading	0
dose	0
of	0
200	0
mg	0
/	0
m2	0
followed	0
by	0
12	0
mg	0
/	0
m2	0
every	0
three	0
hours	0
for	0
six	0
doses	0
and	0
then	0
every	0
six	0
hours	0
until	0
the	0
plasma	0
methotrexate	1
level	0
decreased	0
to	0
less	0
than	0
1	0
X	0
10	0
(	0
-	0
7	0
)	0
mol	0
/	0
L	0
.	0
The	0
mean	0
steady	0
-	0
state	0
plasma	0
and	0
CSF	0
methotrexate	1
concentrations	0
achieved	0
were	0
1	0
.	0
1	0
X	0
10	0
(	0
-	0
3	0
)	0
mol	0
/	0
L	0
and	0
3	0
.	0
6	0
X	0
10	0
(	0
-	0
5	0
)	0
mol	0
/	0
L	0
","	0
respectively	0
.	0
All	0
20	0
patients	0
responded	0
to	0
this	0
regimen	0
","	0
16	0
/	0
20	0
(	0
80	0
%	0
)	0
achieved	0
a	0
complete	0
remission	0
","	0
and	0
20	0
%	0
obtained	0
a	0
partial	0
remission	0
.	0
The	0
most	0
common	0
toxicities	3
encountered	0
were	0
transient	0
serum	0
transaminase	0
and	0
bilirubin	1
elevations	0
","	0
neutropenia	3
","	0
and	0
mucositis	3
.	0
0ne	0
patient	0
had	0
focal	0
seizures	3
and	0
transient	3
hemiparesis	4
but	0
recovered	0
completely	0
.	0
High	0
-	0
dose	0
intravenous	0
methotrexate	1
is	0
an	0
effective	0
treatment	0
for	0
the	0
induction	0
of	0
remission	0
after	0
meningeal	0
relapse	0
in	0
acute	3
lymphoblastic	4
leukemia	4
.	0
Interaction	0
of	0
cyclosporin	1
A	2
with	0
antineoplastic	0
agents	0
.	0
A	0
synergistic	0
effect	0
of	0
etoposide	1
and	0
cyclosporin	1
A	2
was	0
observed	0
in	0
a	0
patient	0
with	0
acute	3
T	4
-	4
lymphocytic	4
leukemia	4
in	0
relapse	0
.	0
The	0
concomitant	0
administration	0
of	0
etoposide	1
and	0
cyclosporin	1
A	2
resulted	0
in	0
eradication	0
of	0
hitherto	0
refractory	0
leukemic	3
infiltration	4
of	0
bone	0
marrow	0
.	0
Severe	0
side	0
effects	0
in	0
terms	0
of	0
mental	0
confusion	3
and	0
progressive	0
hyperbilirubinemia	3
","	0
however	0
","	0
point	0
to	0
an	0
enhancement	0
not	0
only	0
of	0
antineoplastic	0
effects	0
but	0
also	0
of	0
toxicity	3
in	0
normal	0
tissues	0
.	0
This	0
report	0
demonstrates	0
for	0
the	0
first	0
time	0
that	0
the	0
pharmacodynamic	0
properties	0
of	0
cyclosporin	1
A	2
may	0
not	0
be	0
confined	0
strictly	0
to	0
suppression	0
of	0
normal	0
T	0
-	0
cell	0
functions	0
.	0
Incidence	0
of	0
neoplasms	3
in	0
patients	0
with	0
rheumatoid	3
arthritis	4
exposed	0
to	0
different	0
treatment	0
regimens	0
.	0
Immunosuppressive	0
drugs	0
have	0
been	0
used	0
during	0
the	0
last	0
30	0
years	0
in	0
treatment	0
of	0
patients	0
with	0
severe	0
rheumatoid	3
arthritis	4
.	0
The	0
drugs	0
commonly	0
used	0
are	0
cyclophosphamide	1
and	0
chlorambucil	1
(	0
alkylating	1
agents	2
)	0
","	0
azathioprine	1
(	0
purine	1
analogue	0
)	0
","	0
and	0
methotrexate	1
(	0
folic	1
acid	2
analogue	0
)	0
.	0
There	0
is	0
evidence	0
that	0
all	0
four	0
immunosuppressive	0
drugs	0
can	0
reduce	0
synovitis	3
","	0
but	0
disease	0
activity	0
almost	0
always	0
recurs	0
after	0
therapy	0
is	0
stopped	0
.	0
Since	0
adverse	0
reactions	0
are	0
frequent	0
","	0
less	0
than	0
50	0
percent	0
of	0
patients	0
are	0
able	0
to	0
continue	0
a	0
particular	0
drug	0
for	0
more	0
than	0
one	0
year	0
.	0
Since	0
it	0
takes	0
three	0
to	0
12	0
months	0
to	0
achieve	0
maximal	0
effects	0
","	0
those	0
patients	0
who	0
are	0
unable	0
to	0
continue	0
the	0
drug	0
receive	0
little	0
benefit	0
from	0
it	0
.	0
Patients	0
treated	0
with	0
alkylating	1
agents	2
have	0
an	0
increased	0
risk	0
of	0
development	0
of	0
acute	3
nonlymphocytic	4
leukemia	4
","	0
and	0
both	0
alkylating	1
agents	2
and	0
azathioprine	1
are	0
associated	0
with	0
the	0
development	0
of	0
non	3
-	4
Hodgkin	4
'	4
s	4
lymphoma	4
.	0
Cyclophosphamide	1
therapy	0
increases	0
the	0
risk	0
of	0
carcinoma	3
of	4
the	4
bladder	4
.	0
There	0
have	0
been	0
several	0
long	0
-	0
term	0
studies	0
of	0
patients	0
with	0
rheumatoid	3
arthritis	4
treated	0
with	0
azathioprine	1
and	0
cyclophosphamide	1
and	0
the	0
incidence	0
of	0
most	0
of	0
the	0
common	0
cancers	3
is	0
not	0
increased	0
.	0
Data	0
on	0
the	0
possible	0
increased	0
risk	0
of	0
malignancy	3
in	0
rheumatoid	3
arthritis	4
are	0
still	0
being	0
collected	0
","	0
and	0
until	0
further	0
information	0
is	0
available	0
","	0
the	0
use	0
of	0
immunosuppressive	0
drugs	0
","	0
particularly	0
alkylating	1
agents	2
","	0
in	0
the	0
treatment	0
of	0
rheumatoid	3
arthritis	4
should	0
be	0
reserved	0
for	0
patients	0
with	0
severe	0
progressive	0
disease	0
or	0
life	0
-	0
threatening	0
complications	0
.	0
Warfarin	1
-	0
induced	0
iliopsoas	0
hemorrhage	3
with	0
subsequent	0
femoral	3
nerve	4
palsy	4
.	0
We	0
present	0
the	0
case	0
of	0
a	0
28	0
-	0
year	0
-	0
old	0
man	0
on	0
chronic	0
warfarin	1
therapy	0
who	0
sustained	0
a	0
minor	0
muscle	3
tear	4
and	0
developed	0
increasing	0
pain	3
and	0
a	0
flexure	0
contracture	3
of	0
the	0
right	0
hip	0
.	0
Surgical	0
exploration	0
revealed	0
an	0
iliopsoas	0
hematoma	3
and	0
femoral	0
nerve	3
entrapment	4
","	0
resulting	0
in	0
a	0
femoral	3
nerve	4
palsy	4
and	0
partial	3
loss	4
of	4
quadriceps	4
functions	4
.	0
Anticoagulant	0
-	0
induced	0
femoral	3
nerve	4
palsy	4
represents	0
the	0
most	0
common	0
form	0
of	0
warfarin	1
-	0
induced	0
peripheral	3
neuropathy	4
;	0
it	0
is	0
characterized	0
by	0
severe	0
pain	3
in	0
the	0
inguinal	0
region	0
","	0
varying	0
degrees	0
of	0
motor	3
and	4
sensory	4
impairment	4
","	0
and	0
flexure	0
contracture	3
of	0
the	0
involved	0
extremity	0
.	0
Pneumonitis	0
with	0
pleural	3
and	4
pericardial	4
effusion	4
and	0
neuropathy	3
during	0
amiodarone	1
therapy	0
.	0
A	0
patient	0
with	0
sinuatrial	3
disease	4
and	0
implanted	0
pacemaker	0
was	0
treated	0
with	0
amiodarone	1
(	0
maximum	0
dose	0
1000	0
mg	0
","	0
maintenance	0
dose	0
800	0
mg	0
daily	0
)	0
for	0
10	0
months	0
","	0
for	0
control	0
of	0
supraventricular	3
tachyarrhythmias	4
.	0
He	0
developed	0
pneumonitis	3
","	0
pleural	3
and	4
pericardial	4
effusions	4
","	0
and	0
a	0
predominantly	0
proximal	3
motor	4
neuropathy	4
.	0
Immediate	0
but	0
gradual	0
improvement	0
followed	0
withdrawal	0
of	0
amiodarone	1
and	0
treatment	0
with	0
prednisolone	1
.	0
Review	0
of	0
this	0
and	0
previously	0
reported	0
cases	0
indicates	0
the	0
need	0
for	0
early	0
diagnosis	0
of	0
amiodarone	1
pneumonitis	3
","	0
immediate	0
withdrawal	0
of	0
amiodarone	1
","	0
and	0
prompt	0
but	0
continued	0
steroid	1
therapy	0
to	0
ensure	0
full	0
recovery	0
.	0
Amiodarone	1
-	0
induced	0
sinoatrial	3
block	4
.	0
We	0
observed	0
sinoatrial	3
block	4
due	0
to	0
chronic	0
amiodarone	1
administration	0
in	0
a	0
5	0
-	0
year	0
-	0
old	0
boy	0
with	0
primary	3
cardiomyopathy	4
","	0
Wolff	3
-	4
Parkinson	4
-	4
White	4
syndrome	4
and	0
supraventricular	3
tachycardia	4
.	0
Reduction	0
in	0
the	0
dosage	0
of	0
amiodarone	1
resulted	0
in	0
the	0
disappearance	0
of	0
the	0
sinoatrial	3
block	4
and	0
the	0
persistence	0
of	0
asymptomatic	0
sinus	3
bradycardia	4
.	0
Desipramine	1
-	0
induced	0
delirium	3
at	0
"	0
subtherapeutic	0
"	0
concentrations	0
:	0
a	0
case	0
report	0
.	0
An	0
elderly	0
patient	0
treated	0
with	0
low	0
dose	0
Desipramine	1
developed	0
a	0
delirium	3
while	0
her	0
plasma	0
level	0
was	0
in	0
the	0
"	0
subtherapeutic	0
"	0
range	0
.	0
Delirium	3
","	0
which	0
may	0
be	0
induced	0
by	0
tricyclic	0
drug	0
therapy	0
in	0
the	0
elderly	0
","	0
can	0
be	0
caused	0
by	0
tricyclics	0
with	0
low	0
anticholinergic	0
potency	0
.	0
Therapeutic	0
ranges	0
for	0
antidepressants	1
that	0
have	0
been	0
derived	0
from	0
general	0
adult	0
population	0
studies	0
may	0
not	0
be	0
appropriate	0
for	0
the	0
elderly	0
.	0
Further	0
studies	0
of	0
specifically	0
elderly	0
patients	0
are	0
now	0
required	0
to	0
establish	0
safer	0
and	0
more	0
appropriate	0
guidelines	0
for	0
drug	0
therapy	0
.	0
Indomethacin	1
-	0
induced	0
renal	3
insufficiency	4
:	0
recurrence	0
on	0
rechallenge	0
.	0
We	0
have	0
reported	0
a	0
case	0
of	0
acute	0
oliguric	0
renal	3
failure	4
with	0
hyperkalemia	3
in	0
a	0
patient	0
with	0
cirrhosis	3
","	0
ascites	3
","	0
and	0
cor	3
pulmonale	4
after	0
indomethacin	1
therapy	0
.	0
Prompt	0
restoration	0
of	0
renal	0
function	0
followed	0
drug	0
withdrawal	0
","	0
while	0
re	0
-	0
exposure	0
to	0
a	0
single	0
dose	0
of	0
indomethacin	1
caused	0
recurrence	0
of	0
acute	0
reversible	0
oliguria	3
.	0
0ur	0
case	0
supports	0
the	0
hypothesis	0
that	0
endogenous	0
renal	0
prostaglandins	1
play	0
a	0
role	0
in	0
the	0
maintenance	0
of	0
renal	0
blood	0
flow	0
when	0
circulating	0
plasma	0
volume	0
is	0
diminished	0
.	0
Since	0
nonsteroidal	0
anti	0
-	0
inflammatory	0
agents	0
interfere	0
with	0
this	0
compensatory	0
mechanism	0
and	0
may	0
cause	0
acute	3
renal	4
failure	4
","	0
they	0
should	0
be	0
used	0
with	0
caution	0
in	0
such	0
patients	0
.	0
Patterns	0
of	0
hepatic	3
injury	4
induced	0
by	0
methyldopa	1
.	0
Twelve	0
patients	0
with	0
liver	3
disease	4
related	0
to	0
methyldopa	1
were	0
seen	0
between	0
1967	0
and	0
1977	0
.	0
Illness	0
occurred	0
within	0
1	0
-	0
-	0
9	0
weeks	0
of	0
commencement	0
of	0
therapy	0
in	0
9	0
patients	0
","	0
the	0
remaining	0
3	0
patients	0
having	0
received	0
the	0
drug	0
for	0
13	0
months	0
","	0
15	0
months	0
and	0
7	0
years	0
before	0
experiencing	0
symptoms	0
.	0
Jaundice	3
with	0
tender	0
hepatomegaly	3
","	0
usually	0
preceded	0
by	0
symptoms	0
of	0
malaise	0
","	0
anorexia	3
","	0
nausea	3
and	0
vomiting	3
","	0
and	0
associated	0
with	0
upper	0
abdominal	3
pain	4
","	0
was	0
an	0
invariable	0
finding	0
in	0
all	0
patients	0
.	0
Biochemical	0
liver	0
function	0
tests	0
indicated	0
hepatocellular	0
necrosis	3
and	0
correlated	0
with	0
histopathological	0
evidence	0
of	0
hepatic	3
injury	4
","	0
the	0
spectrum	0
of	0
which	0
ranged	0
from	0
fatty	3
change	4
and	0
focal	0
hepatocellular	0
necrosis	3
to	0
massive	3
hepatic	4
necrosis	4
.	0
Most	0
patients	0
showed	0
moderate	0
to	0
severe	0
acute	3
hepatitis	4
or	0
chronic	3
active	4
hepatitis	4
with	0
associated	0
cholestasis	3
.	0
The	0
drug	0
was	0
withdrawn	0
on	0
presentation	0
to	0
hospital	0
in	0
11	0
patients	0
","	0
with	0
rapid	0
clinical	0
improvement	0
in	0
9	0
.	0
0ne	0
patient	0
died	0
","	0
having	0
presented	0
in	0
hepatic	3
failure	4
","	0
and	0
another	0
","	0
who	0
had	0
been	0
taking	0
methyldopa	1
for	0
7	0
years	0
","	0
showed	0
slower	0
clinical	0
and	0
biochemical	0
resolution	0
over	0
a	0
period	0
of	0
several	0
months	0
.	0
The	0
remaining	0
patient	0
in	0
the	0
series	0
developed	0
fulminant	3
hepatitis	4
when	0
the	0
drug	0
was	0
accidentally	0
recommenced	0
1	0
year	0
after	0
a	0
prior	0
episode	0
of	0
methyldopa	1
-	0
induced	0
hepatitis	3
.	0
In	0
this	0
latter	0
patient	0
","	0
and	0
in	0
2	0
others	0
","	0
the	0
causal	0
relationship	0
between	0
methyldopa	1
and	0
hepatic	3
dysfunction	4
was	0
proved	0
with	0
the	0
recurrence	0
of	0
hepatitis	3
within	0
2	0
weeks	0
of	0
re	0
-	0
exposure	0
to	0
the	0
drug	0
.	0
Suxamethonium	1
infusion	0
rate	0
and	0
observed	0
fasciculations	3
.	0
A	0
dose	0
-	0
response	0
study	0
.	0
Suxamethonium	1
chloride	2
(	0
Sch	1
)	0
was	0
administered	0
i	0
.	0
v	0
.	0
to	0
36	0
adult	0
males	0
at	0
six	0
rates	0
:	0
0	0
.	0
25	0
mg	0
s	0
-	0
1	0
to	0
20	0
mg	0
s	0
-	0
1	0
.	0
The	0
infusion	0
was	0
discontinued	0
either	0
when	0
there	0
was	0
no	0
muscular	0
response	0
to	0
tetanic	3
stimulation	0
of	0
the	0
ulnar	0
nerve	0
or	0
when	0
Sch	1
120	0
mg	0
was	0
exceeded	0
.	0
Six	0
additional	0
patients	0
received	0
a	0
30	0
-	0
mg	0
i	0
.	0
v	0
.	0
bolus	0
dose	0
.	0
Fasciculations	3
in	0
six	0
areas	0
of	0
the	0
body	0
were	0
scored	0
from	0
0	0
to	0
3	0
and	0
summated	0
as	0
a	0
total	0
fasciculation	3
score	0
.	0
The	0
times	0
to	0
first	0
fasciculation	3
","	0
twitch	3
suppression	0
and	0
tetanus	3
suppression	0
were	0
inversely	0
related	0
to	0
the	0
infusion	0
rates	0
.	0
Fasciculations	3
in	0
the	0
six	0
areas	0
and	0
the	0
total	0
fasciculation	3
score	0
were	0
related	0
directly	0
to	0
the	0
rate	0
of	0
infusion	0
.	0
Total	0
fasciculation	3
scores	0
in	0
the	0
30	0
-	0
mg	0
bolus	0
group	0
and	0
the	0
5	0
-	0
mg	0
s	0
-	0
1	0
and	0
20	0
-	0
mg	0
s	0
-	0
1	0
infusion	0
groups	0
were	0
not	0
significantly	0
different	0
.	0
Treatment	0
of	0
psoriasis	3
with	0
azathioprine	1
.	0
Azathioprine	1
treatment	0
benefited	0
19	0
(	0
66	0
%	0
)	0
out	0
of	0
29	0
patients	0
suffering	0
from	0
severe	0
psoriasis	3
.	0
Haematological	0
complications	0
were	0
not	0
troublesome	0
and	0
results	0
of	0
biochemical	0
liver	0
function	0
tests	0
remained	0
normal	0
.	0
Minimal	0
cholestasis	3
was	0
seen	0
in	0
two	0
cases	0
and	0
portal	0
fibrosis	3
of	0
a	0
reversible	0
degree	0
in	0
eight	0
.	0
Liver	0
biopsies	0
should	0
be	0
undertaken	0
at	0
regular	0
intervals	0
if	0
azathioprine	1
therapy	0
is	0
continued	0
so	0
that	0
structural	0
liver	3
damage	4
may	0
be	0
detected	0
at	0
an	0
early	0
and	0
reversible	0
stage	0
.	0
Angiosarcoma	3
of	4
the	4
liver	4
associated	0
with	0
diethylstilbestrol	1
.	0
Angiosarcoma	3
of	4
the	4
liver	4
occurred	0
in	0
a	0
76	0
-	0
year	0
-	0
old	0
man	0
who	0
had	0
been	0
treated	0
for	0
a	0
well	0
-	0
differentiated	0
adenocarcinoma	3
of	4
the	4
liver	4
with	0
diethylstilbestrol	1
for	0
13	0
years	0
.	0
Angiosarcoma	3
was	0
also	0
present	0
within	0
pulmonary	0
and	0
renal	0
arteries	0
.	0
The	0
possibility	0
that	0
the	0
intraarterial	3
lesions	4
might	0
represent	0
independent	0
primary	0
tumors	3
is	0
considered	0
.	0
Galanthamine	1
hydrobromide	2
","	0
a	0
longer	0
acting	0
anticholinesterase	0
drug	0
","	0
in	0
the	0
treatment	0
of	0
the	0
central	0
effects	0
of	0
scopolamine	1
(	0
Hyoscine	1
)	0
.	0
Galanthamine	1
hydrobromide	2
","	0
an	0
anticholinesterase	0
drug	0
capable	0
of	0
penetrating	0
the	0
blood	0
-	0
brain	0
barrier	0
","	0
was	0
used	0
in	0
a	0
patient	0
demonstrating	0
central	0
effects	0
of	0
scopolamine	1
(	0
hyoscine	1
)	0
overdosage	3
.	0
It	0
is	0
longer	0
acting	0
than	0
physostigmine	1
and	0
is	0
used	0
in	0
anaesthesia	0
to	0
reverse	0
the	0
non	0
-	0
depolarizing	0
neuromuscular	0
block	0
.	0
However	0
","	0
studies	0
into	0
the	0
dose	0
necessary	0
to	0
combating	0
scopolamine	1
intoxication	0
are	0
indicated	0
.	0
Comparison	0
of	0
the	0
subjective	0
effects	0
and	0
plasma	0
concentrations	0
following	0
oral	0
and	0
i	0
.	0
m	0
.	0
administration	0
of	0
flunitrazepam	1
in	0
volunteers	0
.	0
Flunitrazepam	1
0	0
.	0
5	0
","	0
1	0
.	0
0	0
or	0
2	0
.	0
0	0
mg	0
was	0
given	0
by	0
the	0
oral	0
or	0
i	0
.	0
m	0
.	0
routes	0
to	0
groups	0
of	0
volunteers	0
and	0
its	0
effects	0
compared	0
.	0
Plasma	0
concentrations	0
of	0
the	0
drug	0
were	0
estimated	0
by	0
gas	0
-	0
liquid	0
chromatography	0
","	0
in	0
a	0
smaller	0
number	0
of	0
the	0
subjects	0
.	0
The	0
most	0
striking	0
effect	0
was	0
sedation	0
which	0
increased	0
with	0
the	0
dose	0
","	0
2	0
mg	0
producing	0
deep	0
sleep	0
although	0
the	0
subjects	0
could	0
still	0
be	0
aroused	0
.	0
The	0
effects	0
of	0
i	0
.	0
m	0
.	0
administration	0
were	0
apparent	0
earlier	0
and	0
sometimes	0
lasted	0
longer	0
than	0
those	0
following	0
oral	0
administration	0
.	0
Dizziness	3
was	0
less	0
marked	0
than	0
sedation	0
","	0
but	0
increased	0
with	0
the	0
dose	0
.	0
There	0
was	0
pain	3
on	0
i	0
.	0
m	0
.	0
injection	0
of	0
flunitrazepam	1
significantly	0
more	0
often	0
than	0
with	0
isotonic	0
saline	0
.	0
Plasma	0
concentrations	0
varied	0
with	0
dose	0
and	0
route	0
and	0
corresponded	0
qualitatively	0
with	0
the	0
subjective	0
effects	0
.	0
The	0
drug	0
was	0
still	0
present	0
in	0
measurable	0
quantities	0
after	0
24	0
h	0
even	0
with	0
the	0
smallest	0
dose	0
.	0
Possible	0
teratogenicity	0
of	0
sulphasalazine	1
.	0
Three	0
infants	0
","	0
born	0
of	0
two	0
mothers	0
with	0
inflammatory	3
bowel	4
disease	4
who	0
received	0
treatment	0
with	0
sulphasalazine	1
throughout	0
pregnancy	0
","	0
were	0
found	0
to	0
have	0
major	0
congenital	3
anomalies	4
.	0
In	0
the	0
singleton	0
pregnancy	0
","	0
the	0
mother	0
had	0
ulcerative	3
colitis	4
","	0
and	0
the	0
infant	0
","	0
a	0
male	0
","	0
had	0
coarctation	3
of	4
the	4
aorta	4
and	0
a	0
ventricular	3
septal	4
defect	4
.	0
In	0
the	0
twin	0
pregnancy	0
","	0
the	0
mother	0
had	0
Crohn	3
'	4
s	4
disease	4
.	0
The	0
first	0
twin	0
","	0
a	0
female	0
","	0
had	0
a	0
left	0
Potter	3
-	4
type	4
IIa	4
polycystic	4
kidney	4
and	0
a	0
rudimentary	3
left	4
uterine	4
cornu	4
.	0
The	0
second	0
twin	0
","	0
a	0
male	0
","	0
had	0
some	0
features	0
of	0
Potter	3
'	4
s	4
facies	4
","	0
hypoplastic	3
lungs	4
","	0
absent	3
kidneys	4
and	4
ureters	4
","	0
and	0
talipes	3
equinovarus	4
.	0
Despite	0
reports	0
to	0
the	0
contrary	0
","	0
it	0
is	0
suggested	0
that	0
sulphasalazine	1
may	0
be	0
teratogenic	0
.	0
Thrombotic	3
microangiopathy	4
and	0
renal	3
failure	4
associated	0
with	0
antineoplastic	0
chemotherapy	0
.	0
Five	0
patients	0
with	0
carcinoma	3
developed	0
thrombotic	3
microangiopathy	4
(	0
characterized	0
by	0
renal	3
insufficiency	4
","	0
microangiopathic	3
hemolytic	4
anemia	4
","	0
and	0
usually	0
thrombocytopenia	3
)	0
after	0
treatment	0
with	0
cisplatin	1
","	0
bleomycin	1
","	0
and	0
a	0
vinca	1
alkaloid	2
.	0
0ne	0
patient	0
had	0
thrombotic	3
thrombocytopenic	4
purpura	4
","	0
three	0
the	0
hemolytic	3
-	4
uremic	4
syndrome	4
","	0
and	0
one	0
an	0
apparent	0
forme	0
fruste	0
of	0
one	0
of	0
these	0
disorders	0
.	0
Histologic	0
examination	0
of	0
the	0
renal	0
tissue	0
showed	0
evidence	0
of	0
intravascular	3
coagulation	4
","	0
primarily	0
affecting	0
the	0
small	0
arteries	0
","	0
arterioles	0
","	0
and	0
glomeruli	0
.	0
Because	0
each	0
patient	0
was	0
tumor	3
-	0
free	0
or	0
had	0
only	0
a	0
small	0
tumor	3
at	0
the	0
onset	0
of	0
this	0
syndrome	0
","	0
the	0
thrombotic	3
microangiopathy	4
may	0
have	0
been	0
induced	0
by	0
chemotherapy	0
.	0
Diagnosis	0
of	0
this	0
potentially	0
fatal	0
complication	0
may	0
be	0
delayed	0
or	0
missed	0
if	0
renal	0
tissue	0
or	0
the	0
peripheral	0
blood	0
smear	0
is	0
not	0
examined	0
","	0
because	0
renal	3
failure	4
may	0
be	0
ascribed	0
to	0
cisplatin	1
nephrotoxicity	3
and	0
the	0
anemia	3
and	0
thrombocytopenia	3
to	0
drug	0
-	0
induced	0
bone	3
marrow	4
suppression	4
.	0
International	0
mexiletine	1
and	0
placebo	0
antiarrhythmic	0
coronary	0
trial	0
:	0
I	0
.	0
Report	0
on	0
arrhythmia	3
and	0
other	0
findings	0
.	0
Impact	0
Research	0
Group	0
.	0
The	0
antiarrhythmic	0
effects	0
of	0
the	0
sustained	0
release	0
form	0
of	0
mexiletine	1
(	0
Mexitil	1
-	2
Perlongets	2
)	0
were	0
evaluated	0
in	0
a	0
double	0
-	0
blind	0
placebo	0
trial	0
in	0
630	0
patients	0
with	0
recent	0
documented	0
myocardial	3
infarction	4
.	0
The	0
primary	0
response	0
variable	0
was	0
based	0
on	0
central	0
reading	0
of	0
24	0
hour	0
ambulatory	0
electrocardiographic	0
recordings	0
and	0
was	0
defined	0
as	0
the	0
occurrence	0
of	0
30	0
or	0
more	0
single	0
premature	0
ventricular	0
complexes	0
in	0
any	0
two	0
consecutive	0
30	0
minute	0
blocks	0
or	0
one	0
or	0
more	0
runs	0
of	0
two	0
or	0
more	0
premature	0
ventricular	0
complexes	0
in	0
the	0
entire	0
24	0
hour	0
electrocardiographic	0
recording	0
.	0
Large	0
differences	0
","	0
regarded	0
as	0
statistically	0
significant	0
","	0
between	0
the	0
mexiletine	1
and	0
placebo	0
groups	0
were	0
noted	0
in	0
that	0
end	0
point	0
at	0
months	0
1	0
and	0
4	0
","	0
but	0
only	0
trends	0
were	0
observed	0
at	0
month	0
12	0
.	0
These	0
differences	0
were	0
observed	0
even	0
though	0
the	0
serum	0
mexiletine	1
levels	0
obtained	0
in	0
this	0
study	0
were	0
generally	0
lower	0
than	0
those	0
observed	0
in	0
studies	0
that	0
have	0
used	0
the	0
regular	0
form	0
of	0
the	0
drug	0
.	0
There	0
were	0
more	0
deaths	3
in	0
the	0
mexiletine	1
group	0
(	0
7	0
.	0
6	0
%	0
)	0
than	0
in	0
the	0
placebo	0
group	0
(	0
4	0
.	0
8	0
%	0
)	0
;	0
the	0
difference	0
was	0
not	0
statistically	0
significant	0
.	0
The	0
incidence	0
of	0
coronary	0
events	0
was	0
similar	0
in	0
both	0
groups	0
.	0
Previously	0
recognized	0
side	0
effects	0
","	0
particularly	0
tremor	3
and	0
gastrointestinal	3
problems	4
","	0
were	0
more	0
frequent	0
in	0
the	0
mexiletine	1
group	0
than	0
in	0
the	0
placebo	0
group	0
.	0
Changes	0
in	0
heart	0
size	0
during	0
long	0
-	0
term	0
timolol	1
treatment	0
after	0
myocardial	3
infarction	4
.	0
The	0
effect	0
of	0
long	0
-	0
term	0
timolol	1
treatment	0
on	0
heart	0
size	0
after	0
myocardial	3
infarction	4
was	0
evaluated	0
by	0
X	0
-	0
ray	0
in	0
a	0
double	0
-	0
blind	0
study	0
including	0
241	0
patients	0
(	0
placebo	0
126	0
","	0
timolol	1
115	0
)	0
.	0
The	0
follow	0
-	0
up	0
period	0
was	0
12	0
months	0
.	0
The	0
timolol	1
-	0
treated	0
patients	0
showed	0
a	0
small	0
but	0
significant	0
increase	0
in	0
heart	0
size	0
from	0
baseline	0
in	0
contrast	0
to	0
a	0
decrease	0
in	0
the	0
placebo	0
group	0
.	0
These	0
differences	0
may	0
be	0
caused	0
by	0
timolol	1
-	0
induced	0
bradycardia	3
and	0
a	0
compensatory	0
increase	0
in	0
end	0
-	0
diastolic	0
volume	0
.	0
The	0
timolol	1
-	0
related	0
increase	0
in	0
heart	0
size	0
was	0
observed	0
only	0
in	0
patients	0
with	0
normal	0
and	0
borderline	0
heart	0
size	0
.	0
In	0
patients	0
with	0
cardiomegaly	3
","	0
the	0
increase	0
in	0
heart	0
size	0
was	0
similar	0
in	0
both	0
groups	0
.	0
After	0
re	0
-	0
infarction	3
","	0
heart	0
size	0
increased	0
in	0
the	0
placebo	0
group	0
and	0
remained	0
unchanged	0
in	0
the	0
timolol	1
group	0
.	0
Vitamin	1
D3	2
toxicity	3
in	0
dairy	0
cows	0
.	0
Large	0
parenteral	0
doses	0
of	0
vitamin	1
D3	2
(	0
15	0
to	0
17	0
.	0
5	0
x	0
10	0
(	0
6	0
)	0
IU	0
vitamin	1
D3	2
)	0
were	0
associated	0
with	0
prolonged	0
hypercalcemia	3
","	0
hyperphosphatemia	3
","	0
and	0
large	0
increases	0
of	0
vitamin	1
D3	2
and	0
its	0
metabolites	0
in	0
the	0
blood	0
plasma	0
of	0
nonlactating	0
nonpregnant	0
and	0
pregnant	0
Jersey	0
cows	0
.	0
Calcium	1
concentrations	0
1	0
day	0
postpartum	0
were	0
higher	0
in	0
cows	0
treated	0
with	0
vitamin	1
D3	2
about	0
32	0
days	0
prepartum	0
(	0
8	0
.	0
8	0
mg	0
/	0
100	0
ml	0
)	0
than	0
in	0
control	0
cows	0
(	0
5	0
.	0
5	0
mg	0
/	0
100	0
ml	0
)	0
.	0
None	0
of	0
the	0
cows	0
treated	0
with	0
vitamin	1
D3	2
showed	0
signs	0
of	0
milk	3
fever	4
during	0
the	0
peripartal	0
period	0
;	0
however	0
","	0
22	0
%	0
of	0
the	0
control	0
cows	0
developed	0
clinical	0
signs	0
of	0
milk	3
fever	4
during	0
this	0
period	0
.	0
Signs	0
of	0
vitamin	1
D3	2
toxicity	3
were	0
not	0
observed	0
in	0
nonlactating	0
nonpregnant	0
cows	0
;	0
however	0
","	0
pregnant	0
cows	0
commonly	0
developed	0
severe	0
signs	0
of	0
vitamin	1
D3	2
toxicity	3
and	0
10	0
of	0
17	0
cows	0
died	0
.	0
There	0
was	0
widespread	0
metastatic	0
calcification	0
in	0
the	0
cows	0
that	0
died	0
.	0
Because	0
of	0
the	0
extreme	0
toxicity	3
of	0
vitamin	1
D3	2
in	0
pregnant	0
Jersey	0
cows	0
and	0
the	0
low	0
margin	0
of	0
safety	0
between	0
doses	0
of	0
vitamin	1
D3	2
that	0
prevent	0
milk	3
fever	4
and	0
doses	0
that	0
induce	0
milk	3
fever	4
","	0
we	0
concluded	0
that	0
vitamin	1
D3	2
cannot	0
be	0
used	0
practically	0
to	0
prevent	0
milk	3
fever	4
when	0
injected	0
several	0
weeks	0
prepartum	0
.	0
Diseases	3
of	4
peripheral	4
nerves	4
as	0
seen	0
in	0
the	0
Nigerian	0
African	0
.	0
The	0
anatomical	0
and	0
aetiological	0
diagnoses	0
of	0
peripheral	3
nerve	4
disease	4
excluding	0
its	0
primary	0
benign	0
and	0
malignant	0
disorders	0
","	0
as	0
seen	0
in	0
358	0
Nigerians	0
are	0
presented	0
.	0
There	0
is	0
a	0
male	0
preponderance	0
and	0
the	0
peak	0
incidence	0
is	0
in	0
the	0
fourth	0
decade	0
.	0
Sensori	3
-	4
motor	4
neuropathy	4
was	0
the	0
commonest	0
presentation	0
(	0
50	0
%	0
)	0
.	0
Guillain	3
-	4
Barr	4
syndrome	4
was	0
the	0
commonest	0
identifiable	0
cause	0
(	0
15	0
.	0
6	0
%	0
)	0
","	0
accounting	0
for	0
half	0
of	0
the	0
cases	0
with	0
motor	3
neuropathy	4
.	0
Peripheral	3
neuropathy	4
due	0
to	0
nutritional	3
deficiency	4
of	0
thiamine	1
and	0
riboflavin	1
was	0
common	0
(	0
10	0
.	0
1	0
%	0
)	0
and	0
presented	0
mainly	0
as	0
sensory	0
and	0
sensori	3
-	4
motor	4
neuropathy	4
.	0
Diabetes	3
mellitus	4
was	0
the	0
major	0
cause	0
of	0
autonomic	3
neuropathy	4
.	0
Isoniazid	1
was	0
the	0
most	0
frequent	0
agent	0
in	0
drug	0
-	0
induced	0
neuropathy	3
.	0
Migraine	3
(	0
20	0
%	0
)	0
was	0
not	0
an	0
uncommon	0
cause	0
of	0
cranial	3
neuropathy	4
although	0
malignancies	3
arising	0
from	0
the	0
reticuloendothelial	0
system	0
or	0
related	0
structures	0
of	0
the	0
head	0
and	0
neck	0
were	0
more	0
frequent	0
(	0
26	0
%	0
)	0
.	0
In	0
26	0
.	0
5	0
%	0
of	0
all	0
the	0
cases	0
","	0
the	0
aetiology	0
of	0
the	0
neuropathy	3
was	0
undetermined	0
.	0
Heredofamilial	0
and	0
connective	3
tissue	4
disorders	4
were	0
rare	0
.	0
Some	0
of	0
the	0
factors	0
related	0
to	0
the	0
clinical	0
presentation	0
and	0
pathogenesis	0
of	0
the	0
neuropathies	3
are	0
briefly	0
discussed	0
.	0
Reduction	0
in	0
caffeine	1
toxicity	3
by	0
acetaminophen	1
.	0
A	0
patient	0
who	0
allegedly	0
consumed	0
100	0
tablets	0
of	0
an	0
over	0
-	0
the	0
-	0
counter	0
analgesic	0
containing	0
sodium	1
acetylsalicylate	2
","	0
caffeine	1
","	0
and	0
acetaminophen	1
displayed	0
no	0
significant	0
CNS	0
stimulation	0
despite	0
the	0
presence	0
of	0
175	0
micrograms	0
of	0
caffeine	1
per	0
mL	0
of	0
serum	0
.	0
Because	0
salicylates	0
have	0
been	0
reported	0
to	0
augment	0
the	0
stimulatory	0
effects	0
of	0
caffeine	1
on	0
the	0
CNS	0
","	0
attention	0
was	0
focused	0
on	0
the	0
possibility	0
that	0
the	0
presence	0
of	0
acetaminophen	1
(	0
52	0
micrograms	0
/	0
mL	0
)	0
reduced	0
the	0
CNS	0
toxicity	3
of	0
caffeine	1
.	0
Studies	0
in	0
DBA	0
/	0
2J	0
mice	0
showed	0
that	0
:	0
1	0
)	0
pretreatment	0
with	0
acetaminophen	1
(	0
100	0
mg	0
/	0
kg	0
)	0
increased	0
the	0
interval	0
between	0
the	0
administration	0
of	0
caffeine	1
(	0
300	0
to	0
450	0
mg	0
/	0
kg	0
IP	0
)	0
and	0
the	0
onset	0
of	0
fatal	0
convulsions	3
by	0
a	0
factor	0
of	0
about	0
two	0
;	0
and	0
2	0
)	0
pretreatment	0
with	0
acetaminophen	1
(	0
75	0
mg	0
/	0
kg	0
)	0
reduced	0
the	0
incidence	0
of	0
audiogenic	0
seizures	3
produced	0
in	0
the	0
presence	0
of	0
caffeine	1
(	0
12	0
.	0
5	0
to	0
75	0
mg	0
/	0
kg	0
IP	0
)	0
.	0
The	0
frequency	0
of	0
sound	0
-	0
induced	0
seizures	3
after	0
12	0
.	0
5	0
or	0
25	0
mg	0
/	0
kg	0
caffeine	1
was	0
reduced	0
from	0
50	0
to	0
5	0
%	0
by	0
acetaminophen	1
.	0
In	0
the	0
absence	0
of	0
caffeine	1
","	0
acetaminophen	1
(	0
up	0
to	0
300	0
mg	0
/	0
kg	0
)	0
did	0
not	0
modify	0
the	0
seizures	3
induced	0
by	0
maximal	0
electroshock	0
and	0
did	0
not	0
alter	0
the	0
convulsant	0
dose	0
of	0
pentylenetetrezol	1
in	0
mice	0
(	0
tests	0
performed	0
by	0
the	0
Anticonvulsant	0
Screening	0
Project	0
of	0
NINCDS	0
)	0
.	0
Acetaminophen	1
(	0
up	0
to	0
150	0
micrograms	0
/	0
mL	0
)	0
did	0
not	0
retard	0
the	0
incorporation	0
of	0
radioactive	0
adenosine	1
into	0
ATP	1
in	0
slices	0
of	0
rat	0
cerebral	0
cortex	0
.	0
Thus	0
the	0
mechanism	0
by	0
which	0
acetaminophen	1
antagonizes	0
the	0
actions	0
of	0
caffeine	1
in	0
the	0
CNS	0
remains	0
unknown	0
.	0
A	0
double	0
-	0
blind	0
study	0
of	0
the	0
efficacy	0
and	0
safety	0
of	0
dothiepin	1
hydrochloride	2
in	0
the	0
treatment	0
of	0
major	0
depressive	3
disorder	4
.	0
In	0
a	0
6	0
-	0
week	0
double	0
-	0
blind	0
parallel	0
treatment	0
study	0
","	0
dothiepin	1
and	0
amitriptyline	1
were	0
compared	0
to	0
placebo	0
in	0
the	0
treatment	0
of	0
33	0
depressed	3
outpatients	0
.	0
Dothiepin	1
and	0
amitriptyline	1
were	0
equally	0
effective	0
in	0
alleviating	0
the	0
symptoms	0
of	0
depressive	3
illness	4
","	0
and	0
both	0
were	0
significantly	0
superior	0
to	0
placebo	0
.	0
The	0
overall	0
incidence	0
of	0
side	0
effects	0
and	0
the	0
frequency	0
and	0
severity	0
of	0
blurred	3
vision	4
","	0
dry	3
mouth	4
","	0
and	0
drowsiness	0
were	0
significantly	0
less	0
with	0
dothiepin	1
than	0
with	0
amitriptyline	1
.	0
Dothiepin	1
also	0
produced	0
fewer	0
CNS	0
and	0
cardiovascular	0
effects	0
.	0
There	0
were	0
no	0
clinically	0
important	0
changes	0
in	0
laboratory	0
parameters	0
.	0
Dothiepin	1
thus	0
was	0
found	0
to	0
be	0
an	0
effective	0
antidepressant	1
drug	0
associated	0
with	0
fewer	0
side	0
effects	0
than	0
amitriptyline	1
in	0
the	0
treatment	0
of	0
depressed	3
outpatients	0
.	0
Behavioral	0
effects	0
of	0
diazepam	1
and	0
propranolol	1
in	0
patients	0
with	0
panic	3
disorder	4
and	0
agoraphobia	3
.	0
The	0
effects	0
of	0
oral	0
doses	0
of	0
diazepam	1
(	0
single	0
dose	0
of	0
10	0
mg	0
and	0
a	0
median	0
dose	0
of	0
30	0
mg	0
/	0
day	0
for	0
2	0
weeks	0
)	0
and	0
propranolol	1
(	0
single	0
dose	0
of	0
80	0
mg	0
and	0
a	0
median	0
dose	0
of	0
240	0
mg	0
/	0
day	0
for	0
2	0
weeks	0
)	0
on	0
psychological	0
performance	0
of	0
patients	0
with	0
panic	3
disorders	4
and	0
agoraphobia	3
were	0
investigated	0
in	0
a	0
double	0
-	0
blind	0
","	0
randomized	0
and	0
crossover	0
design	0
.	0
Both	0
drugs	0
impaired	3
immediate	4
free	4
recall	4
but	0
the	0
decrease	0
was	0
greater	0
for	0
diazepam	1
than	0
propranolol	1
.	0
Delayed	3
free	4
recall	4
was	4
also	4
impaired	4
but	0
the	0
two	0
drugs	0
did	0
not	0
differ	0
.	0
Patients	0
tapped	0
faster	0
after	0
propranolol	1
than	0
diazepam	1
and	0
they	0
were	0
more	0
sedated	0
after	0
diazepam	1
than	0
propranolol	1
.	0
After	0
2	0
weeks	0
of	0
treatment	0
","	0
patients	0
tested	0
5	0
-	0
8	0
h	0
after	0
the	0
last	0
dose	0
of	0
medication	0
did	0
not	0
show	0
any	0
decrement	0
of	0
performance	0
.	0
These	0
results	0
are	0
similar	0
to	0
those	0
previously	0
found	0
in	0
healthy	0
subjects	0
.	0
Accumulation	0
of	0
drugs	0
was	0
not	0
reflected	0
in	0
prolonged	0
behavioral	3
impairment	4
.	0
Comparison	0
of	0
i	0
.	0
v	0
.	0
glycopyrrolate	1
and	0
atropine	1
in	0
the	0
prevention	0
of	0
bradycardia	3
and	0
arrhythmias	3
following	0
repeated	0
doses	0
of	0
suxamethonium	1
in	0
children	0
.	0
The	0
effectiveness	0
of	0
administration	0
of	0
glycopyrrolate	1
5	0
and	0
10	0
micrograms	0
kg	0
-	0
1	0
and	0
atropine	1
10	0
and	0
20	0
micrograms	0
kg	0
-	0
1	0
i	0
.	0
v	0
.	0
immediately	0
before	0
the	0
induction	0
of	0
anaesthesia	0
","	0
to	0
prevent	0
arrhythmia	3
and	0
bradycardia	3
following	0
repeated	0
doses	0
of	0
suxamethonium	1
in	0
children	0
","	0
was	0
studied	0
.	0
A	0
control	0
group	0
was	0
included	0
for	0
comparison	0
with	0
the	0
lower	0
dose	0
range	0
of	0
glycopyrrolate	1
and	0
atropine	1
.	0
A	0
frequency	0
of	0
bradycardia	3
of	0
50	0
%	0
was	0
noted	0
in	0
the	0
control	0
group	0
","	0
but	0
this	0
was	0
not	0
significantly	0
different	0
from	0
the	0
frequency	0
with	0
the	0
active	0
drugs	0
.	0
Bradycardia	3
(	0
defined	0
as	0
a	0
decrease	0
in	0
heart	0
rate	0
to	0
less	0
than	0
50	0
beat	0
min	0
-	0
1	0
)	0
was	0
prevented	0
when	0
the	0
larger	0
dose	0
of	0
either	0
active	0
drug	0
was	0
used	0
.	0
It	0
is	0
recommended	0
that	0
either	0
glycopyrrolate	1
10	0
micrograms	0
kg	0
-	0
1	0
or	0
atropine	1
20	0
micrograms	0
kg	0
-	0
1	0
i	0
.	0
v	0
.	0
should	0
immediately	0
precede	0
induction	0
of	0
anaesthesia	0
","	0
in	0
children	0
","	0
if	0
the	0
repeated	0
administration	0
of	0
suxamethonium	1
is	0
anticipated	0
.	0
Veno	3
-	4
occlusive	4
liver	4
disease	4
after	0
dacarbazine	1
therapy	0
(	0
DTIC	1
)	0
for	0
melanoma	3
.	0
A	0
case	0
of	0
veno	3
-	4
occlusive	4
disease	4
of	4
the	4
liver	4
with	0
fatal	0
outcome	0
after	0
dacarbazine	1
(	0
DTIC	1
)	0
therapy	0
for	0
melanoma	3
is	0
reported	0
.	0
There	0
was	0
a	0
fulminant	0
clinical	0
course	0
from	0
start	0
of	0
symptoms	0
until	0
death	3
.	0
At	0
autopsy	0
the	0
liver	0
was	0
enlarged	0
and	0
firm	0
with	0
signs	0
of	0
venous	3
congestion	4
.	0
Small	0
-	0
and	0
medium	0
-	0
sized	0
hepatic	0
veins	0
were	0
blocked	0
by	0
thrombosis	3
.	0
Eosinophilic	0
infiltrations	0
were	0
found	0
around	0
the	0
vessels	0
.	0
Published	0
cases	0
from	0
the	0
literature	0
are	0
reviewed	0
and	0
pertinent	0
features	0
discussed	0
.	0
Maternal	0
lithium	1
and	0
neonatal	0
Ebstein	3
'	4
s	4
anomaly	4
:	0
evaluation	0
with	0
cross	0
-	0
sectional	0
echocardiography	0
.	0
Cross	0
-	0
sectional	0
echocardiography	0
was	0
used	0
to	0
evaluate	0
two	0
neonates	0
whose	0
mothers	0
ingested	0
lithium	1
during	0
pregnancy	0
.	0
In	0
one	0
infant	0
","	0
Ebstein	3
'	4
s	4
anomaly	4
of	0
the	0
tricuspid	0
valve	0
was	0
identified	0
.	0
In	0
the	0
other	0
infant	0
cross	0
-	0
sectional	0
echocardiography	0
provided	0
reassurance	0
that	0
the	0
infant	0
did	0
not	0
have	0
Ebstein	3
'	4
s	4
anomaly	4
.	0
Cross	0
-	0
sectional	0
echocardiographic	0
screening	0
of	0
newborns	0
exposed	0
to	0
lithium	1
during	0
gestation	0
can	0
provide	0
highly	0
accurate	0
","	0
noninvasive	0
assessment	0
of	0
the	0
presence	0
or	0
absence	0
of	0
lithium	1
-	0
induced	0
cardiac	3
malformations	4
.	0
Effects	0
of	0
training	0
on	0
the	0
extent	0
of	0
experimental	0
myocardial	3
infarction	4
in	0
aging	0
rats	0
.	0
The	0
effects	0
of	0
exercise	0
on	0
the	0
severity	0
of	0
isoproterenol	1
-	0
induced	0
myocardial	3
infarction	4
were	0
studied	0
in	0
female	0
albino	0
rats	0
of	0
20	0
","	0
40	0
","	0
60	0
and	0
80	0
weeks	0
of	0
age	0
.	0
The	0
rats	0
were	0
trained	0
to	0
swim	0
for	0
a	0
specific	0
duration	0
and	0
for	0
a	0
particular	0
period	0
.	0
The	0
occurrence	0
of	0
infarcts	3
were	0
confirmed	0
by	0
histological	0
methods	0
.	0
Elevations	0
in	0
the	0
serum	0
G0T	0
and	0
GPT	0
were	0
maximum	0
in	0
the	0
sedentary	0
-	0
isoproterenols	1
and	0
minimum	0
in	0
the	0
exercise	0
-	0
controls	0
.	0
These	0
changes	0
in	0
the	0
serum	0
transaminases	0
were	0
associated	0
with	0
corresponding	0
depletions	0
in	0
the	0
cardiac	0
G0T	0
and	0
GPT	0
.	0
However	0
","	0
age	0
was	0
seen	0
to	0
interfere	0
with	0
the	0
responses	0
exhibited	0
by	0
the	0
young	0
and	0
old	0
rats	0
.	0
Studies	0
dealing	0
with	0
myocardial	3
infarction	4
are	0
more	0
informative	0
when	0
dealt	0
with	0
age	0
.	0
Effect	0
of	0
polyethylene	1
glycol	2
400	2
on	0
adriamycin	1
toxicity	3
in	0
mice	0
.	0
The	0
effect	0
of	0
a	0
widely	0
used	0
organic	0
solvent	0
","	0
polyethylene	1
glycol	2
400	2
(	0
PEG	1
400	2
)	0
","	0
on	0
the	0
toxic	0
action	0
of	0
an	0
acute	0
or	0
chronic	0
treatment	0
with	0
adriamycin	1
(	0
ADR	1
)	0
was	0
evaluated	0
in	0
mice	0
.	0
PEG	1
400	2
impressively	0
decreased	0
both	0
acute	0
high	0
-	0
dose	0
and	0
chronic	0
low	0
-	0
dose	0
-	0
ADR	1
-	0
associated	0
lethality	0
.	0
Light	0
microscopic	0
analysis	0
showed	0
a	0
significant	0
protection	0
against	0
ADR	1
-	0
induced	0
cardiac	3
morphological	4
alterations	4
.	0
Such	0
treatment	0
did	0
not	0
diminish	0
the	0
ADR	1
antitumor	0
activity	0
in	0
L1210	3
leukemia	4
and	0
in	0
Ehrlich	3
ascites	4
tumor	4
.	0
Sublingual	0
absorption	0
of	0
the	0
quaternary	1
ammonium	2
antiarrhythmic	0
agent	0
","	0
UM	1
-	2
272	2
.	0
UM	1
-	2
272	2
(	0
N	1
","	2
N	2
-	2
dimethylpropranolol	2
)	0
","	0
a	0
quaternary	0
antiarrhythmic	0
agent	0
","	0
was	0
administered	0
sublingually	0
to	0
dogs	0
with	0
ouabain	1
-	0
induced	0
ventricular	3
tachycardias	4
.	0
Both	0
anti	0
-	0
arrhythmic	0
efficacy	0
and	0
bioavailability	0
were	0
compared	0
to	0
oral	0
drug	0
.	0
Sublingual	0
UM	1
-	2
272	2
converted	0
ventricular	3
tachycardia	4
to	0
sinus	0
rhythm	0
in	0
all	0
5	0
dogs	0
.	0
The	0
area	0
under	0
the	0
plasma	0
concentration	0
time	0
curve	0
at	0
90	0
min	0
was	0
4	0
-	0
12	0
times	0
greater	0
than	0
for	0
oral	0
drug	0
","	0
suggesting	0
the	0
existence	0
of	0
an	0
absorption	0
-	0
limiting	0
process	0
in	0
the	0
intestine	0
","	0
and	0
providing	0
an	0
alternate	0
form	0
of	0
administration	0
for	0
quaternary	0
drugs	0
.	0
Early	0
adjuvant	0
adriamycin	1
in	0
superficial	0
bladder	3
carcinoma	4
.	0
A	0
multicenter	0
study	0
was	0
performed	0
in	0
110	0
patients	0
with	0
superficial	0
transitional	0
cell	0
carcinoma	3
of	4
the	4
bladder	4
.	0
Adriamycin	1
(	0
50	0
mg	0
/	0
50	0
ml	0
)	0
was	0
administered	0
intravesically	0
within	0
24	0
h	0
after	0
transurethral	0
resection	0
of	0
TA	0
-	0
T1	0
(	0
0	0
-	0
A	0
)	0
bladder	3
tumors	4
.	0
Instillation	0
was	0
repeated	0
twice	0
during	0
the	0
first	0
week	0
","	0
then	0
weekly	0
during	0
the	0
first	0
month	0
and	0
afterwards	0
monthly	0
for	0
1	0
year	0
.	0
The	0
tolerance	0
was	0
evaluated	0
in	0
these	0
110	0
patients	0
","	0
and	0
29	0
patients	0
presented	0
with	0
local	0
side	0
-	0
effects	0
.	0
In	0
24	0
of	0
these	0
patients	0
chemical	0
cystitis	3
was	0
severe	0
enough	0
for	0
them	0
to	0
drop	0
out	0
of	0
the	0
study	0
.	0
No	0
systemic	0
side	0
-	0
effects	0
were	0
observed	0
.	0
Recurrence	0
was	0
studied	0
in	0
82	0
evaluable	0
patients	0
after	0
1	0
year	0
of	0
follow	0
-	0
up	0
and	0
in	0
72	0
patients	0
followed	0
for	0
2	0
-	0
3	0
years	0
(	0
mean	0
32	0
months	0
)	0
.	0
0f	0
the	0
82	0
patients	0
studied	0
after	0
1	0
year	0
","	0
23	0
had	0
primary	0
and	0
59	0
recurrent	0
disease	0
.	0
0f	0
the	0
82	0
evaluable	0
patients	0
","	0
50	0
did	0
not	0
show	0
any	0
recurrence	0
after	0
1	0
year	0
(	0
61	0
%	0
)	0
","	0
while	0
32	0
presented	0
with	0
one	0
or	0
more	0
recurrences	0
(	0
39	0
%	0
)	0
.	0
0f	0
these	0
recurrences	0
","	0
27	0
were	0
T1	0
tumors	3
while	0
five	0
progressed	0
to	0
more	0
highly	0
invasive	0
lesions	0
.	0
In	0
patients	0
that	0
were	0
free	0
of	0
recurrence	0
during	0
the	0
first	0
year	0
","	0
80	0
%	0
remained	0
tumor	3
-	0
free	0
during	0
the	0
2	0
-	0
to	0
3	0
-	0
year	0
follow	0
-	0
up	0
period	0
.	0
0f	0
the	0
patients	0
developing	0
one	0
or	0
more	0
recurrences	0
during	0
the	0
first	0
year	0
","	0
only	0
50	0
%	0
presented	0
with	0
further	0
recurrence	0
once	0
the	0
instillations	0
were	0
stopped	0
.	0
The	0
beneficial	0
effect	0
of	0
Adriamycin	1
appears	0
obvious	0
and	0
might	0
be	0
related	0
to	0
the	0
drug	0
itself	0
","	0
the	0
early	0
and	0
repeated	0
instillations	0
after	0
TUR	0
","	0
or	0
both	0
.	0
D	1
-	2
penicillamine	2
-	0
induced	0
angiopathy	3
in	0
rats	0
.	0
The	0
effect	0
of	0
high	0
dose	0
D	1
-	2
penicillamine	2
treatment	0
on	0
aortic	0
permeability	0
to	0
albumin	0
and	0
on	0
the	0
ultrastructure	0
of	0
the	0
vessel	0
.	0
Male	0
Sprague	0
-	0
Dawley	0
rats	0
were	0
treated	0
with	0
D	1
-	2
penicillamine	2
(	0
D	1
-	2
pen	2
)	0
500	0
mg	0
/	0
kg	0
/	0
day	0
for	0
10	0
or	0
42	0
days	0
.	0
Pair	0
fed	0
rats	0
served	0
as	0
controls	0
.	0
Changes	0
in	0
aortic	0
morphology	0
were	0
examined	0
by	0
light	0
-	0
and	0
transmission	0
-	0
electron	0
microscopy	0
(	0
TEM	0
)	0
.	0
In	0
addition	0
","	0
the	0
endothelial	0
permeability	0
and	0
the	0
penetration	0
through	0
the	0
aortic	0
wall	0
of	0
albumin	0
were	0
studied	0
10	0
minutes	0
","	0
24	0
and	0
48	0
hours	0
after	0
i	0
.	0
v	0
.	0
injection	0
of	0
human	0
serum	0
131I	0
-	0
albumin	0
(	0
131I	0
-	0
HSA	0
)	0
.	0
TEM	0
revealed	0
extensive	0
elastolysis	0
in	0
the	0
arterial	0
wall	0
of	0
D	1
-	2
pen	2
-	0
treated	0
rats	0
","	0
consistent	0
with	0
an	0
inhibitory	0
effect	0
on	0
crosslink	0
formation	0
.	0
In	0
experimental	0
animals	0
excess	0
deposition	0
of	0
collagen	0
and	0
glycoaminoglycans	0
was	0
observed	0
in	0
the	0
subendothelial	0
and	0
medial	0
layer	0
of	0
the	0
aortic	0
wall	0
","	0
together	0
with	0
prominent	0
basal	0
membrane	0
substance	0
around	0
aortic	0
smooth	0
muscle	0
cells	0
.	0
The	0
aorta	0
/	0
serum	0
-	0
ratio	0
and	0
the	0
radioactive	0
build	0
-	0
up	0
24	0
and	0
48	0
hours	0
after	0
injection	0
of	0
131I	0
-	0
HSA	0
was	0
reduced	0
in	0
animals	0
treated	0
with	0
D	1
-	2
pen	2
for	0
42	0
days	0
","	0
indicating	0
an	0
impeded	0
transmural	0
transport	0
of	0
tracer	0
which	0
may	0
be	0
caused	0
by	0
a	0
steric	0
exclusion	0
effect	0
of	0
abundant	0
hyaluronate	1
.	0
The	0
endothelial	0
ultrastructure	0
was	0
unaffected	0
by	0
D	1
-	2
pen	2
","	0
and	0
no	0
differences	0
in	0
aortic	0
131I	0
-	0
HSA	0
radioactivity	0
or	0
aorta	0
/	0
serum	0
-	0
ratio	0
were	0
recorded	0
between	0
experimental	0
and	0
control	0
groups	0
10	0
minutes	0
after	0
tracer	0
injection	0
","	0
indicating	0
that	0
the	0
permeability	0
of	0
the	0
endothelial	0
barrier	0
to	0
albumin	0
remained	0
unaffected	0
by	0
D	1
-	2
pen	2
treatment	0
.	0
These	0
observations	0
support	0
the	0
hypothesis	0
that	0
treatment	0
with	0
high	0
doses	0
of	0
D	1
-	2
pen	2
may	0
induce	0
a	0
fibroproliferative	0
response	0
in	0
rat	0
aorta	0
","	0
possibly	0
by	0
an	0
inhibitory	0
effect	0
on	0
the	0
cross	0
-	0
linking	0
of	0
collagen	0
and	0
elastin	0
.	0
Effect	0
of	0
aspirin	1
on	0
N	1
-	2
[	2
4	2
-	2
(	2
5	2
-	2
nitro	2
-	2
2	2
-	2
furyl	2
)	2
-	2
2	2
-	2
thiazolyl	2
]	2
-	2
formamide	2
-	0
induced	0
epithelial	0
proliferation	0
in	0
the	0
urinary	0
bladder	0
and	0
forestomach	0
of	0
the	0
rat	0
.	0
The	0
co	0
-	0
administration	0
of	0
aspirin	1
with	0
N	1
-	2
[	2
4	2
-	2
(	2
5	2
-	2
nitro	2
-	2
2	2
-	2
furyl	2
)	2
-	2
2	2
-	2
thiazolyl	2
]	2
-	2
formamide	2
(	0
FANFT	1
)	0
to	0
rats	0
resulted	0
in	0
a	0
reduced	0
incidence	0
of	0
FANFT	1
-	0
induced	0
bladder	3
carcinomas	4
but	0
a	0
concomitant	0
induction	0
of	0
forestomach	3
tumors	4
.	0
An	0
autoradiographic	0
study	0
was	0
performed	0
on	0
male	0
F	0
-	0
344	0
rats	0
fed	0
diet	0
containing	0
FANFT	1
at	0
a	0
level	0
of	0
0	0
.	0
2	0
%	0
and	0
/	0
or	0
aspirin	1
at	0
a	0
level	0
of	0
0	0
.	0
5	0
%	0
to	0
evaluate	0
the	0
effect	0
of	0
aspirin	1
on	0
the	0
increased	0
cell	0
proliferation	0
induced	0
by	0
FANFT	1
in	0
the	0
forestomach	0
and	0
bladder	0
.	0
FANFT	1
-	0
induced	0
cell	0
proliferation	0
in	0
the	0
bladder	0
was	0
significantly	0
suppressed	0
by	0
aspirin	1
co	0
-	0
administration	0
after	0
4	0
weeks	0
but	0
not	0
after	0
12	0
weeks	0
.	0
In	0
the	0
forestomach	0
","	0
and	0
also	0
in	0
the	0
liver	0
","	0
aspirin	1
did	0
not	0
affect	0
the	0
FANFT	1
-	0
induced	0
increase	0
in	0
labeling	0
index	0
.	0
The	0
present	0
results	0
are	0
consistent	0
with	0
the	0
carcinogenicity	0
experiment	0
suggesting	0
that	0
different	0
mechanisms	0
are	0
involved	0
in	0
FANFT	1
carcinogenesis	3
in	0
the	0
bladder	0
and	0
forestomach	0
","	0
and	0
that	0
aspirin	1
'	0
s	0
effect	0
on	0
FANFT	1
in	0
the	0
forestomach	0
is	0
not	0
due	0
to	0
an	0
irritant	0
effect	0
associated	0
with	0
increased	0
cell	0
proliferation	0
.	0
Also	0
","	0
there	0
appears	0
to	0
be	0
an	0
adaptation	0
by	0
the	0
rats	0
to	0
the	0
chronic	0
ingestion	0
of	0
aspirin	1
.	0
A	0
case	0
of	0
tardive	3
dyskinesia	4
caused	0
by	0
metoclopramide	1
.	0
Abnormal	3
involuntary	4
movements	4
appeared	0
in	0
the	0
mouth	0
","	0
tongue	0
","	0
neck	0
and	0
abdomen	0
of	0
a	0
64	0
-	0
year	0
-	0
old	0
male	0
patient	0
after	0
he	0
took	0
metoclopramide	1
for	0
gastrointestinal	3
disorder	4
in	0
a	0
regimen	0
of	0
30	0
mg	0
per	0
day	0
for	0
a	0
total	0
of	0
about	0
260	0
days	0
.	0
The	0
symptoms	0
exacerbated	0
to	0
a	0
maximum	0
in	0
a	0
month	0
.	0
When	0
the	0
metoclopramide	1
administration	0
was	0
discontinued	0
","	0
the	0
abnormal	3
movements	4
gradually	0
improved	0
to	0
a	0
considerable	0
extent	0
.	0
Attention	0
to	0
the	0
possible	0
induction	0
of	0
specific	0
tardive	3
dyskinesia	4
is	0
called	0
for	0
in	0
the	0
use	0
of	0
this	0
drug	0
.	0
Intra	0
-	0
arterial	0
BCNU	1
chemotherapy	0
for	0
treatment	0
of	0
malignant	3
gliomas	4
of	0
the	0
central	0
nervous	0
system	0
.	0
Because	0
of	0
the	0
rapid	0
systemic	0
clearance	0
of	0
BCNU	1
(	0
1	1
","	2
3	2
-	2
bis	2
-	2
(	2
2	2
-	2
chloroethyl	2
)	2
-	2
1	2
-	2
nitrosourea	2
)	0
","	0
intra	0
-	0
arterial	0
administration	0
should	0
provide	0
a	0
substantial	0
advantage	0
over	0
intravenous	0
administration	0
for	0
the	0
treatment	0
of	0
malignant	3
gliomas	4
.	0
Thirty	0
-	0
six	0
patients	0
were	0
treated	0
with	0
BCNU	1
every	0
6	0
to	0
8	0
weeks	0
","	0
either	0
by	0
transfemoral	0
catheterization	0
of	0
the	0
internal	0
carotid	0
or	0
vertebral	0
artery	0
or	0
through	0
a	0
fully	0
implantable	0
intracarotid	0
drug	0
delivery	0
system	0
","	0
beginning	0
with	0
a	0
dose	0
of	0
200	0
mg	0
/	0
sq	0
m	0
body	0
surface	0
area	0
.	0
Twelve	0
patients	0
with	0
Grade	0
III	0
or	0
IV	0
astrocytomas	3
were	0
treated	0
after	0
partial	0
resection	0
of	0
the	0
tumor	3
without	0
prior	0
radiation	0
therapy	0
.	0
After	0
two	0
to	0
seven	0
cycles	0
of	0
chemotherapy	0
","	0
nine	0
patients	0
showed	0
a	0
decrease	0
in	0
tumor	3
size	0
and	0
surrounding	0
edema	3
on	0
contrast	0
-	0
enhanced	0
computerized	0
tomography	0
scans	0
.	0
In	0
the	0
nine	0
responders	0
","	0
median	0
duration	0
of	0
chemotherapy	0
response	0
from	0
the	0
time	0
of	0
operation	0
was	0
25	0
weeks	0
(	0
range	0
12	0
to	0
more	0
than	0
91	0
weeks	0
)	0
.	0
The	0
median	0
duration	0
of	0
survival	0
in	0
the	0
12	0
patients	0
was	0
54	0
weeks	0
(	0
range	0
21	0
to	0
more	0
than	0
156	0
weeks	0
)	0
","	0
with	0
an	0
18	0
-	0
month	0
survival	0
rate	0
of	0
42	0
%	0
.	0
Twenty	0
-	0
four	0
patients	0
with	0
recurrent	0
Grade	0
I	0
to	0
IV	0
astrocytomas	3
","	0
whose	0
resection	0
and	0
irradiation	0
therapy	0
had	0
failed	0
","	0
received	0
two	0
to	0
eight	0
courses	0
of	0
intra	0
-	0
arterial	0
BCNU	1
therapy	0
.	0
Seventeen	0
of	0
these	0
had	0
a	0
response	0
or	0
were	0
stable	0
for	0
a	0
median	0
of	0
20	0
weeks	0
(	0
range	0
6	0
to	0
more	0
than	0
66	0
weeks	0
)	0
.	0
The	0
catheterization	0
procedure	0
is	0
safe	0
","	0
with	0
no	0
immediate	0
complication	0
in	0
111	0
infusions	0
of	0
BCNU	1
.	0
A	0
delayed	0
complication	0
in	0
nine	0
patients	0
has	0
been	0
unilateral	0
loss	3
of	4
vision	4
secondary	0
to	0
a	0
retinal	3
vasculitis	4
.	0
The	0
frequency	0
of	0
visual	3
loss	4
decreased	0
after	0
the	0
concentration	0
of	0
the	0
ethanol	1
diluent	0
was	0
lowered	0
.	0
Provocation	0
of	0
postural	0
hypotension	3
by	0
nitroglycerin	1
in	0
diabetic	3
autonomic	4
neuropathy	4
?	0
The	0
effect	0
of	0
nitroglycerin	1
on	0
heart	0
rate	0
and	0
systolic	0
blood	0
pressure	0
was	0
compared	0
in	0
5	0
normal	0
subjects	0
","	0
12	0
diabetic	3
subjects	0
without	0
autonomic	3
neuropathy	4
","	0
and	0
5	0
diabetic	3
subjects	0
with	0
autonomic	3
neuropathy	4
.	0
The	0
magnitude	0
and	0
time	0
course	0
of	0
the	0
increase	0
in	0
heart	0
rate	0
and	0
the	0
decrease	0
in	0
systolic	0
blood	0
pressure	0
after	0
nitroglycerin	1
were	0
similar	0
in	0
the	0
normal	0
and	0
diabetic	3
subjects	0
without	0
autonomic	3
neuropathy	4
","	0
whereas	0
a	0
lesser	0
increase	0
in	0
heart	0
rate	0
and	0
a	0
greater	0
decrease	0
in	0
systolic	0
blood	0
pressure	0
occurred	0
in	0
the	0
diabetic	3
subjects	0
with	0
autonomic	3
neuropathy	4
.	0
It	0
is	0
therefore	0
suggested	0
that	0
caution	0
should	0
be	0
exercised	0
when	0
prescribing	0
vasodilator	0
drugs	0
in	0
diabetic	3
patients	0
","	0
particularly	0
those	0
with	0
autonomic	3
neuropathy	4
.	0
Blood	0
pressure	0
response	0
to	0
chronic	0
low	0
-	0
dose	0
intrarenal	0
noradrenaline	1
infusion	0
in	0
conscious	0
rats	0
.	0
Sodium	1
chloride	2
solution	0
(	0
0	0
.	0
9	0
%	0
)	0
or	0
noradrenaline	1
in	0
doses	0
of	0
4	0
","	0
12	0
and	0
36	0
micrograms	0
h	0
-	0
1	0
kg	0
-	0
1	0
was	0
infused	0
for	0
five	0
consecutive	0
days	0
","	0
either	0
intrarenally	0
(	0
by	0
a	0
new	0
technique	0
)	0
or	0
intravenously	0
into	0
rats	0
with	0
one	0
kidney	0
removed	0
.	0
Intrarenal	0
infusion	0
of	0
noradrenaline	1
caused	0
hypertension	3
at	0
doses	0
which	0
did	0
not	0
do	0
so	0
when	0
infused	0
intravenously	0
.	0
Intrarenal	0
compared	0
with	0
intravenous	0
infusion	0
of	0
noradrenaline	1
caused	0
higher	0
plasma	0
noradrenaline	1
concentrations	0
and	0
a	0
shift	0
of	0
the	0
plasma	0
noradrenaline	1
concentration	0
-	0
blood	0
pressure	0
effect	0
curve	0
towards	0
lower	0
plasma	0
noradrenaline	1
levels	0
.	0
These	0
results	0
suggest	0
that	0
hypertension	3
after	0
chronic	0
intrarenal	0
noradrenaline	1
infusion	0
is	0
produced	0
by	0
relatively	0
higher	0
levels	0
of	0
circulating	0
noradrenaline	1
and	0
by	0
triggering	0
of	0
an	0
additional	0
intrarenal	0
pressor	0
mechanism	0
.	0
Characterization	0
of	0
estrogen	1
-	0
induced	0
adenohypophyseal	3
tumors	4
in	0
the	0
Fischer	0
344	0
rat	0
.	0
Pituitary	3
tumors	4
were	0
induced	0
in	0
F344	0
female	0
rats	0
by	0
chronic	0
treatment	0
with	0
diethylstilbestrol	1
(	0
DES	1
","	0
8	0
-	0
10	0
mg	0
)	0
implanted	0
subcutaneously	0
in	0
silastic	0
capsules	0
.	0
0ver	0
a	0
range	0
of	0
1	0
-	0
150	0
days	0
of	0
DES	1
treatment	0
","	0
pairs	0
of	0
control	0
and	0
DES	1
-	0
treated	0
rats	0
were	0
sacrificed	0
","	0
and	0
their	0
pituitaries	0
dissociated	0
enzymatically	0
into	0
single	0
-	0
cell	0
preparations	0
.	0
The	0
cell	0
populations	0
were	0
examined	0
regarding	0
total	0
cell	0
recovery	0
correlated	0
with	0
gland	0
weight	0
","	0
intracellular	0
prolactin	0
(	0
PRL	0
)	0
content	0
and	0
subsequent	0
release	0
in	0
primary	0
culture	0
","	0
immunocytochemical	0
PRL	0
staining	0
","	0
density	0
and	0
/	0
or	0
size	0
alterations	0
via	0
separation	0
on	0
Ficoll	0
-	0
Hypaque	0
and	0
by	0
unit	0
gravity	0
sedimentation	0
","	0
and	0
cell	0
cycle	0
analysis	0
","	0
after	0
acriflavine	1
DNA	0
staining	0
","	0
by	0
laser	0
flow	0
cytometry	0
.	0
Total	0
cell	0
yields	0
from	0
DES	1
-	0
treated	0
pituitaries	0
increased	0
from	0
1	0
.	0
3	0
times	0
control	0
yields	0
at	0
8	0
days	0
of	0
treatment	0
to	0
58	0
.	0
9	0
times	0
control	0
values	0
by	0
day	0
150	0
.	0
Intracellular	0
PRL	0
content	0
ranged	0
from	0
1	0
.	0
9	0
to	0
9	0
.	0
4	0
times	0
control	0
levels	0
","	0
and	0
PRL	0
release	0
in	0
vitro	0
was	0
significantly	0
and	0
consistently	0
higher	0
than	0
controls	0
","	0
after	0
at	0
least	0
8	0
days	0
of	0
DES	1
exposure	0
.	0
Beyond	0
8	0
days	0
of	0
DES	1
exposure	0
","	0
the	0
immunochemically	0
PRL	0
-	0
positive	0
proportion	0
of	0
cells	0
increased	0
to	0
over	0
50	0
%	0
of	0
the	0
total	0
population	0
.	0
Increased	0
density	0
and	0
/	0
or	0
size	0
and	0
PRL	0
content	0
were	0
indicated	0
for	0
the	0
majority	0
of	0
the	0
PRL	0
cell	0
population	0
in	0
both	0
types	0
of	0
separation	0
protocols	0
.	0
All	0
these	0
effects	0
of	0
DES	1
were	0
more	0
pronounced	0
among	0
previously	0
ovariectomized	0
animals	0
.	0
The	0
data	0
extend	0
the	0
findings	0
of	0
other	0
investigators	0
","	0
further	0
establishing	0
the	0
DES	1
-	0
induced	0
tumor	3
as	0
a	0
model	0
for	0
study	0
of	0
PRL	0
cellular	0
control	0
mechanisms	0
.	0
Age	0
and	0
renal	0
clearance	0
of	0
cimetidine	1
.	0
In	0
35	0
patients	0
(	0
ages	0
20	0
to	0
86	0
yr	0
)	0
receiving	0
cimetidine	1
therapeutically	0
two	0
serum	0
samples	0
and	0
all	0
urine	0
formed	0
in	0
the	0
interim	0
were	0
collected	0
for	0
analysis	0
of	0
cimetidine	1
by	0
high	0
-	0
pressure	0
liquid	0
chromatography	0
and	0
for	0
creatinine	1
.	0
Cimetidine	1
clearance	0
decreased	0
with	0
age	0
.	0
The	0
extrapolated	0
6	0
-	0
hr	0
serum	0
concentration	0
of	0
cimetidine	1
per	0
unit	0
dose	0
","	0
after	0
intravenous	0
cimetidine	1
","	0
increased	0
with	0
age	0
of	0
the	0
patients	0
.	0
The	0
ratio	0
of	0
cimetidine	1
clearance	0
to	0
creatinine	1
clearance	0
(	0
Rc	0
)	0
averaged	0
4	0
.	0
8	0
+	0
/	0
-	0
2	0
.	0
0	0
","	0
indicating	0
net	0
tubular	0
secretion	0
for	0
cimetidine	1
.	0
Rc	0
seemed	0
to	0
be	0
independent	0
of	0
age	0
and	0
decreased	0
with	0
increasing	0
serum	0
concentration	0
of	0
cimetidine	1
","	0
suggesting	0
that	0
secretion	0
of	0
cimetidine	1
is	0
a	0
saturable	0
process	0
.	0
There	0
was	0
only	0
one	0
case	0
of	0
dementia	3
possibly	0
due	0
to	0
cimetidine	1
(	0
with	0
a	0
drug	0
level	0
of	0
1	0
.	0
9	0
microgram	0
/	0
ml	0
6	0
hr	0
after	0
a	0
dose	0
)	0
in	0
a	0
group	0
of	0
13	0
patients	0
without	0
liver	3
or	4
kidney	4
disease	4
who	0
had	0
cimetidine	1
levels	0
above	0
1	0
.	0
25	0
microgram	0
/	0
ml	0
.	0
Thus	0
","	0
high	0
cimetidine	1
levels	0
alone	0
do	0
not	0
always	0
induce	0
dementia	3
.	0
Further	0
observations	0
on	0
the	0
electrophysiologic	0
effects	0
of	0
oral	0
amiodarone	1
therapy	0
.	0
A	0
case	0
is	0
presented	0
of	0
a	0
reversible	0
intra	3
-	4
Hisian	4
block	4
occurring	0
under	0
amiodarone	1
treatment	0
for	0
atrial	3
tachycardia	4
in	0
a	0
patient	0
without	0
clear	0
intraventricular	3
conduction	4
abnormalities	4
.	0
His	0
bundle	0
recordings	0
showed	0
an	0
atrial	3
tachycardia	4
with	0
intermittent	0
exit	0
block	0
and	0
greatly	0
prolonged	0
BH	0
and	0
HV	0
intervals	0
(	0
40	0
and	0
100	0
msec	0
","	0
respectively	0
)	0
.	0
Thirty	0
days	0
after	0
amiodarone	1
discontinuation	0
","	0
His	0
bundle	0
electrograms	0
showed	0
atrial	3
flutter	4
without	0
intra	0
-	0
Hisian	0
or	0
infra	0
-	0
Hisian	0
delay	0
.	0
Amiodarone	1
should	0
be	0
used	0
with	0
caution	0
during	0
long	0
-	0
term	0
oral	0
therapy	0
in	0
patients	0
with	0
or	0
without	0
clear	0
intraventricular	0
conduction	0
defects	0
.	0
Development	0
of	0
clear	3
cell	4
adenocarcinoma	4
in	0
DES	1
-	0
exposed	0
offspring	0
under	0
observation	0
.	0
Two	0
cases	0
of	0
clear	3
cell	4
adenocarcinoma	4
of	4
the	4
vagina	4
detected	0
at	0
follow	0
-	0
up	0
in	0
young	0
women	0
exposed	0
in	0
utero	0
to	0
diethylstilbestrol	1
are	0
reported	0
.	0
0ne	0
patient	0
","	0
aged	0
23	0
","	0
had	0
been	0
followed	0
for	0
2	0
years	0
before	0
carcinoma	3
was	0
diagnosed	0
;	0
the	0
second	0
patient	0
","	0
aged	0
22	0
","	0
had	0
been	0
seen	0
on	0
a	0
regular	0
basis	0
for	0
5	0
years	0
","	0
8	0
months	0
.	0
In	0
both	0
instances	0
","	0
suspicion	0
of	0
the	0
presence	0
of	0
carcinoma	3
was	0
aroused	0
by	0
the	0
palpation	0
of	0
a	0
small	0
nodule	0
in	0
the	0
vaginal	0
fornix	0
.	0
Hysterosalpingography	0
was	0
performed	0
on	0
both	0
patients	0
and	0
","	0
in	0
1	0
instance	0
","	0
an	0
abnormal	0
x	0
-	0
ray	0
film	0
was	0
reflected	0
by	0
the	0
gross	0
appearance	0
of	0
the	0
uterine	0
cavity	0
found	0
in	0
the	0
surgical	0
specimen	0
.	0
Neurologic	0
effects	0
of	0
subarachnoid	0
administration	0
of	0
2	1
-	2
chloroprocaine	2
-	2
CE	2
","	0
bupivacaine	1
","	0
and	0
low	0
pH	0
normal	0
saline	0
in	0
dogs	0
.	0
The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
evaluate	0
the	0
neurologic	0
consequences	0
of	0
deliberate	0
subarachnoid	0
injection	0
of	0
large	0
volumes	0
of	0
2	1
-	2
chloroprocaine	2
-	2
CE	2
in	0
experimental	0
animals	0
.	0
The	0
possible	0
role	0
of	0
low	0
pH	0
as	0
well	0
as	0
total	0
volume	0
as	0
potential	0
factors	0
in	0
causing	0
neurotoxicity	3
was	0
evaluated	0
.	0
The	0
65	0
dogs	0
in	0
the	0
study	0
received	0
injections	0
in	0
the	0
subarachnoid	0
space	0
as	0
follows	0
:	0
6	0
to	0
8	0
ml	0
of	0
bupivacaine	1
(	0
N	0
=	0
15	0
)	0
","	0
2	1
-	2
chloroprocaine	2
-	2
CE	2
(	0
N	0
=	0
20	0
)	0
","	0
low	0
pH	0
normal	0
saline	0
(	0
pH	0
3	0
.	0
0	0
)	0
(	0
N	0
=	0
20	0
)	0
","	0
or	0
normal	0
saline	0
(	0
N	0
=	0
10	0
)	0
.	0
0f	0
the	0
20	0
animals	0
that	0
received	0
subarachnoid	0
injection	0
of	0
2	1
-	2
chloroprocaine	2
-	2
CE	2
seven	0
(	0
35	0
%	0
)	0
developed	0
hind	0
-	0
limb	0
paralysis	3
.	0
None	0
of	0
the	0
animals	0
that	0
received	0
bupivacaine	1
","	0
normal	0
saline	0
","	0
or	0
normal	0
saline	0
titrated	0
to	0
a	0
pH	0
3	0
.	0
0	0
developed	0
hind	0
-	0
limb	0
paralysis	3
.	0
0f	0
the	0
15	0
spinal	0
cords	0
of	0
the	0
animals	0
that	0
received	0
2	1
-	2
chloroprocaine	2
-	2
CE	2
","	0
13	0
showed	0
subpial	3
necrosis	4
;	0
the	0
nerve	0
roots	0
and	0
subarachnoid	0
vessels	0
were	0
normal	0
.	0
The	0
spinal	0
cords	0
of	0
the	0
animals	0
that	0
received	0
bupivacaine	1
","	0
low	0
pH	0
normal	0
saline	0
(	0
pH	0
3	0
.	0
0	0
)	0
","	0
or	0
normal	0
saline	0
did	0
not	0
show	0
abnormal	0
findings	0
.	0
Procainamide	1
-	0
induced	0
polymorphous	0
ventricular	3
tachycardia	4
.	0
Seven	0
cases	0
of	0
procainamide	1
-	0
induced	0
polymorphous	0
ventricular	3
tachycardia	4
are	0
presented	0
.	0
In	0
four	0
patients	0
","	0
polymorphous	0
ventricular	3
tachycardia	4
appeared	0
after	0
intravenous	0
administration	0
of	0
200	0
to	0
400	0
mg	0
of	0
procainamide	1
for	0
the	0
treatment	0
of	0
sustained	0
ventricular	3
tachycardia	4
.	0
In	0
the	0
remaining	0
three	0
patients	0
","	0
procainamide	1
was	0
administered	0
orally	0
for	0
treatment	0
of	0
chronic	0
premature	3
ventricular	4
contractions	4
or	0
atrial	3
flutter	4
.	0
These	0
patients	0
had	0
Q	3
-	4
T	4
prolongation	4
and	0
recurrent	0
syncope	3
due	0
to	0
polymorphous	0
ventricular	3
tachycardia	4
.	0
In	0
four	0
patients	0
","	0
the	0
arrhythmia	3
was	0
rapidly	0
diagnosed	0
and	0
treated	0
with	0
disappearance	0
of	0
further	0
episodes	0
of	0
the	0
arrhythmia	3
.	0
In	0
two	0
patients	0
","	0
the	0
arrhythmia	3
degenerated	0
into	0
irreversible	0
ventricular	3
fibrillation	4
and	0
both	0
patients	0
died	0
.	0
In	0
the	0
seventh	0
patient	0
","	0
a	0
permanent	0
ventricular	0
pacemaker	0
was	0
inserted	0
and	0
","	0
despite	0
continuation	0
of	0
procainamide	1
therapy	0
","	0
polymorphous	0
ventricular	3
tachycardia	4
did	0
not	0
reoccur	0
.	0
These	0
seven	0
cases	0
demonstrate	0
that	0
procainamide	1
can	0
produce	0
an	0
acquired	0
prolonged	3
Q	4
-	4
T	4
syndrome	4
with	0
polymorphous	0
ventricular	3
tachycardia	4
.	0
Phenobarbitone	1
-	0
induced	0
enlargement	3
of	4
the	4
liver	4
in	0
the	0
rat	0
:	0
its	0
relationship	0
to	0
carbon	1
tetrachloride	2
-	0
induced	0
cirrhosis	3
.	0
The	0
yield	0
of	0
severe	0
cirrhosis	3
of	4
the	4
liver	4
(	0
defined	0
as	0
a	0
shrunken	0
finely	0
nodular	0
liver	0
with	0
micronodular	0
histology	0
","	0
ascites	3
greater	0
than	0
30	0
ml	0
","	0
plasma	0
albumin	0
less	0
than	0
2	0
.	0
2	0
g	0
/	0
dl	0
","	0
splenomegaly	3
2	0
-	0
3	0
times	0
normal	0
","	0
and	0
testicular	0
atrophy	3
approximately	0
half	0
normal	0
weight	0
)	0
after	0
12	0
doses	0
of	0
carbon	1
tetrachloride	2
given	0
intragastrically	0
in	0
the	0
phenobarbitone	1
-	0
primed	0
rat	0
was	0
increased	0
from	0
25	0
%	0
to	0
56	0
%	0
by	0
giving	0
the	0
initial	0
"	0
calibrating	0
"	0
dose	0
of	0
carbon	1
tetrachloride	2
at	0
the	0
peak	0
of	0
the	0
phenobarbitone	1
-	0
induced	0
enlargement	3
of	4
the	4
liver	4
.	0
At	0
this	0
point	0
it	0
was	0
assumed	0
that	0
the	0
cytochrome	0
P450	0
/	0
CCl4	1
toxic	0
state	0
was	0
both	0
maximal	0
and	0
stable	0
.	0
The	0
optimal	0
rat	0
size	0
to	0
begin	0
phenobarbitone	1
was	0
determined	0
as	0
100	0
g	0
","	0
and	0
this	0
size	0
as	0
a	0
group	0
had	0
a	0
mean	0
maximum	0
relative	0
liver	0
weight	0
increase	0
47	0
%	0
greater	0
than	0
normal	0
rats	0
of	0
the	0
same	0
body	0
weight	0
.	0
The	0
optimal	0
time	0
for	0
the	0
initial	0
dose	0
of	0
carbon	1
tetrachloride	2
was	0
after	0
14	0
days	0
on	0
phenobarbitone	1
.	0
Triamterene	1
nephrolithiasis	3
complicating	0
dyazide	1
therapy	0
.	0
A	0
case	0
of	0
triamterene	1
nephrolithiasis	3
is	0
reported	0
in	0
a	0
man	0
after	0
4	0
years	0
of	0
hydrochlorothiazide	1
-	2
triamterene	2
therapy	0
for	0
hypertension	3
.	0
The	0
stone	0
passed	0
spontaneously	0
and	0
was	0
found	0
to	0
contain	0
a	0
triamterene	1
metabolite	0
admixed	0
with	0
uric	1
acid	2
salts	2
.	0
Factors	0
affecting	0
triamterene	1
nephrolithiasis	3
are	0
discussed	0
and	0
2	0
previously	0
reported	0
cases	0
are	0
reviewed	0
.	0
Busulfan	1
-	0
induced	0
hemorrhagic	3
cystitis	4
.	0
A	0
case	0
of	0
a	0
busulfan	1
-	0
induced	0
hemorrhage	3
cystitis	4
is	0
reported	0
.	0
Spontaneous	0
resolution	0
occurred	0
following	0
cessation	0
of	0
the	0
drug	0
.	0
The	0
similarity	0
between	0
the	0
histologic	0
appearances	0
of	0
busulfan	1
cystitis	3
and	0
both	0
radiation	0
and	0
cyclophosphamide	1
-	0
induced	0
cystitis	3
is	0
discussed	0
and	0
the	0
world	0
literature	0
reviewed	0
.	0
In	0
view	0
of	0
the	0
known	0
tendency	0
of	0
busulfan	1
to	0
induce	0
cellular	0
atypia	0
and	0
carcinoma	3
in	0
other	0
sites	0
","	0
periodic	0
urinary	0
cytology	0
is	0
suggested	0
in	0
patients	0
on	0
long	0
-	0
term	0
therapy	0
.	0
Variant	0
ventricular	3
tachycardia	4
in	0
desipramine	1
toxicity	3
.	0
We	0
report	0
a	0
case	0
of	0
variant	0
ventricular	3
tachycardia	4
induced	0
by	0
desipramine	1
toxicity	3
.	0
Unusual	0
features	0
of	0
the	0
arrhythmia	3
are	0
repetitive	0
group	0
beating	0
","	0
progressive	0
shortening	0
of	0
the	0
R	0
-	0
R	0
interval	0
","	0
progressive	0
widening	0
of	0
the	0
QRS	0
complex	0
with	0
eventual	0
failure	0
of	0
intraventricular	0
conduction	0
","	0
and	0
changes	0
in	0
direction	0
of	0
the	0
QRS	0
axis	0
.	0
Recognition	0
of	0
variant	0
ventricular	3
tachycardia	4
is	0
important	0
because	0
therapy	0
differs	0
from	0
that	0
of	0
classic	0
ventricular	3
tachycardia	4
.	0
Rebound	0
hypertensive	3
after	0
sodium	1
nitroprusside	2
prevented	0
by	0
saralasin	1
in	0
rats	0
.	0
The	0
role	0
of	0
the	0
renin	0
-	0
-	0
angiotensin	1
system	0
in	0
the	0
maintenance	0
of	0
blood	0
pressure	0
during	0
halothane	1
anesthesia	0
and	0
sodium	1
nitroprusside	2
(	0
SNP	1
)	0
-	0
induced	0
hypotension	3
was	0
evaluated	0
.	0
Control	0
rats	0
received	0
halothane	1
anesthesia	0
(	0
1	0
MAC	0
)	0
for	0
one	0
hour	0
","	0
followed	0
by	0
SNP	1
infusion	0
","	0
40	0
microgram	0
/	0
kg	0
/	0
min	0
","	0
for	0
30	0
min	0
","	0
followed	0
by	0
a	0
30	0
-	0
min	0
recovery	0
period	0
.	0
A	0
second	0
group	0
of	0
rats	0
was	0
treated	0
identically	0
and	0
","	0
in	0
addition	0
","	0
received	0
an	0
infusion	0
of	0
saralasin	1
(	0
a	0
competitive	0
inhibitor	0
of	0
angiotensin	1
II	2
)	0
throughout	0
the	0
experimental	0
period	0
.	0
In	0
each	0
group	0
","	0
SNP	1
infusion	0
resulted	0
in	0
an	0
initial	0
decrease	0
in	0
blood	0
pressure	0
from	0
86	0
torr	0
and	0
83	0
torr	0
","	0
respectively	0
","	0
to	0
48	0
torr	0
.	0
During	0
the	0
SNP	1
infusion	0
the	0
control	0
animals	0
demonstrated	0
a	0
progressive	0
increase	3
in	4
blood	4
pressure	4
to	0
61	0
torr	0
","	0
whereas	0
the	0
saralasin	1
-	0
treated	0
animals	0
showed	0
no	0
change	0
.	0
Following	0
discontinuation	0
of	0
SNP	1
","	0
blood	0
pressure	0
in	0
the	0
control	0
animals	0
rebounded	0
to	0
94	0
torr	0
","	0
as	0
compared	0
with	0
78	0
torr	0
in	0
the	0
saralasin	1
-	0
treated	0
rats	0
.	0
This	0
study	0
indicates	0
that	0
with	0
stable	0
halothane	1
anesthesia	0
","	0
the	0
partial	0
recovery	0
of	0
blood	0
pressure	0
during	0
SNP	1
infusion	0
and	0
the	0
post	0
-	0
SNP	1
rebound	0
of	0
blood	0
pressure	0
can	0
be	0
completely	0
blocked	0
by	0
saralasin	1
.	0
This	0
demonstrates	0
the	0
participation	0
of	0
the	0
renin	0
-	0
-	0
angiotensin	1
system	0
in	0
antagonizing	0
the	0
combined	0
hypotensive	3
effects	0
of	0
halothane	1
and	0
SNP	1
.	0
Clinical	0
nephrotoxicity	3
of	0
tobramycin	1
and	0
gentamicin	1
.	0
A	0
prospective	0
study	0
.	0
Nearly	0
3	0
.	0
2	0
million	0
people	0
in	0
this	0
country	0
receive	0
aminoglycoside	1
antibiotics	0
annually	0
.	0
Gentamicin	1
sulfate	2
and	0
tobramycin	1
sulfate	2
continue	0
to	0
demonstrate	0
ototoxicity	3
and	0
nephrotoxicity	3
in	0
both	0
animal	0
and	0
clinical	0
studies	0
.	0
In	0
this	0
study	0
","	0
62	0
patients	0
with	0
confirmed	0
initial	0
normal	0
renal	0
function	0
and	0
treated	0
with	0
2	0
to	0
5	0
mg	0
/	0
kg	0
/	0
day	0
of	0
gentamicin	1
sulfate	2
or	0
tobramycin	1
sulfate	2
for	0
a	0
minimum	0
of	0
seven	0
days	0
were	0
followed	0
up	0
prospectively	0
for	0
the	0
development	0
of	0
aminoglycoside	1
-	0
related	0
renal	3
failure	4
","	0
defined	0
as	0
at	0
least	0
a	0
one	0
-	0
third	0
reduction	0
in	0
renal	0
function	0
.	0
In	0
these	0
62	0
patients	0
","	0
no	0
other	0
causes	0
for	0
renal	3
failure	4
could	0
be	0
identified	0
.	0
Five	0
of	0
33	0
(	0
15	0
%	0
)	0
of	0
the	0
tobramycin	1
-	0
treated	0
patients	0
and	0
16	0
of	0
29	0
(	0
55	0
.	0
2	0
%	0
)	0
of	0
the	0
gentamicin	1
-	0
treated	0
patients	0
had	0
renal	3
failure	4
.	0
Thus	0
","	0
gentamicin	1
was	0
associated	0
with	0
renal	3
failure	4
more	0
than	0
three	0
times	0
as	0
often	0
as	0
was	0
tobramycin	1
.	0
Metabolic	0
involvement	0
in	0
adriamycin	1
cardiotoxicity	3
.	0
The	0
cardiotoxic	3
effects	0
of	0
adriamycin	1
were	0
studied	0
in	0
mammalian	0
myocardial	0
cells	0
in	0
culture	0
as	0
a	0
model	0
system	0
.	0
Adriamycin	1
inhibited	0
cell	0
growth	0
and	0
the	0
rhythmic	0
contractions	0
characteristic	0
of	0
myocardial	0
cells	0
in	0
culture	0
.	0
A	0
possible	0
involvement	0
of	0
energy	0
metabolism	0
was	0
suggested	0
previously	0
","	0
and	0
in	0
this	0
study	0
the	0
adenylate	0
energy	0
charge	0
and	0
phosphorylcreatine	1
mole	0
fraction	0
were	0
determined	0
in	0
the	0
adriamycin	1
-	0
treated	0
cells	0
.	0
The	0
adenylate	0
energy	0
charge	0
was	0
found	0
to	0
be	0
significantly	0
decreased	0
","	0
while	0
the	0
phophorylcreatine	1
mole	0
fraction	0
was	0
unchanged	0
.	0
Such	0
disparity	0
suggests	0
an	0
inhibition	0
of	0
creatine	1
phosphokinase	0
.	0
The	0
addition	0
of	0
1	0
mM	0
adenosine	1
to	0
the	0
myocardial	0
cell	0
cultures	0
markedly	0
increases	0
the	0
ATP	1
concentration	0
through	0
a	0
pathway	0
reportedly	0
leading	0
to	0
a	0
compartmentalized	0
ATP	1
pool	0
.	0
In	0
the	0
adriamycin	1
-	0
treated	0
cells	0
","	0
the	0
addition	0
of	0
adenosine	1
increased	0
the	0
adenylate	0
charge	0
and	0
","	0
concomitant	0
with	0
this	0
inrcease	0
","	0
the	0
cells	0
'	0
functional	0
integrity	0
","	0
in	0
terms	0
of	0
percentage	0
of	0
beating	0
cells	0
and	0
rate	0
of	0
contractions	0
","	0
was	0
maintained	0
.	0
Age	0
-	0
dependent	0
sensitivity	0
of	0
the	0
rat	0
to	0
neurotoxic	3
effects	0
of	0
streptomycin	1
.	0
Streptomycin	1
sulfate	0
(	0
300	0
mg	0
/	0
kg	0
s	0
.	0
c	0
.	0
)	0
was	0
injected	0
for	0
various	0
periods	0
into	0
preweanling	0
rats	0
and	0
for	0
3	0
weeks	0
into	0
weanling	0
rats	0
.	0
Beginning	0
at	0
8	0
days	0
of	0
age	0
","	0
body	0
movement	0
and	0
hearing	0
were	0
examined	0
for	0
6	0
and	0
up	0
to	0
17	0
weeks	0
","	0
respectively	0
.	0
Abnormal	3
movements	4
and	0
deafness	3
occurred	0
only	0
in	0
rats	0
treated	0
during	0
the	0
preweaning	0
period	0
;	0
within	0
this	0
period	0
the	0
greatest	0
sensitivities	0
for	0
these	0
abnormalities	0
occurred	0
from	0
2	0
to	0
11	0
-	0
17	0
and	0
5	0
to	0
11	0
days	0
of	0
age	0
","	0
respectively	0
","	0
indicating	0
that	0
the	0
cochlea	0
is	0
more	0
sensitive	0
to	0
streptomycin	1
than	0
the	0
site	0
(	0
vestibular	0
or	0
central	0
)	0
responsible	0
for	0
the	0
dyskinesias	3
.	0
Late	0
","	0
late	0
doxorubicin	1
cardiotoxicity	3
.	0
Cardiac	3
toxicity	4
is	0
a	0
major	0
complication	0
which	0
limits	0
the	0
use	0
of	0
adriamycin	1
as	0
a	0
chemotherapeutic	0
agent	0
.	0
Cardiomyopathy	3
is	0
frequent	0
when	0
the	0
total	0
dose	0
exceeds	0
600	0
mg	0
/	0
m2	0
and	0
occurs	0
within	0
one	0
to	0
six	0
months	0
after	0
cessation	0
of	0
therapy	0
.	0
A	0
patient	0
is	0
reported	0
who	0
developed	0
progressive	0
cardiomyopathy	3
two	0
and	0
one	0
-	0
half	0
years	0
after	0
receiving	0
580	0
mg	0
/	0
m2	0
which	0
apparently	0
represents	0
late	0
","	0
late	0
cardiotoxicity	3
.	0
Attenuation	0
of	0
the	0
lithium	1
-	0
induced	0
diabetes	3
-	4
insipidus	4
-	4
like	4
syndrome	4
by	0
amiloride	1
in	0
rats	0
.	0
The	0
effect	0
of	0
amiloride	1
on	0
lithium	1
-	0
induced	0
polydipsia	3
and	0
polyuria	3
and	0
on	0
the	0
lithium	1
concentration	0
in	0
the	0
plasma	0
","	0
brain	0
","	0
kidney	0
","	0
thyroid	0
and	0
red	0
blood	0
cells	0
was	0
investigated	0
in	0
rats	0
","	0
chronically	0
treated	0
with	0
LiCl	1
.	0
Amiloride	1
reduced	0
the	0
drinking	0
and	0
urine	0
volume	0
of	0
rats	0
in	0
an	0
acute	0
(	0
6	0
or	0
12	0
h	0
)	0
and	0
a	0
subacute	0
(	0
3	0
days	0
)	0
experiment	0
.	0
6	0
h	0
after	0
the	0
administration	0
of	0
amiloride	1
","	0
a	0
reduction	0
was	0
observed	0
in	0
the	0
lithium	1
content	0
of	0
the	0
renal	0
medulla	0
but	0
not	0
in	0
the	0
other	0
organs	0
studied	0
.	0
At	0
12	0
h	0
","	0
all	0
the	0
tissues	0
showed	0
a	0
slight	0
increase	0
in	0
lithium	1
levels	0
.	0
After	0
3	0
days	0
of	0
combined	0
treatment	0
","	0
a	0
marked	0
elevation	0
in	0
plasma	0
and	0
tissue	0
lithium	1
levels	0
accompanied	0
a	0
reduction	0
in	0
water	0
intake	0
.	0
In	0
all	0
the	0
experiments	0
","	0
the	0
attenuation	0
of	0
the	0
lithium	1
-	0
induced	0
diabetes	3
-	4
insipidus	4
-	4
like	4
syndrome	4
by	0
amiloride	1
was	0
accompanied	0
by	0
a	0
reduction	0
of	0
the	0
ratio	0
between	0
the	0
lithium	1
concentration	0
in	0
the	0
renal	0
medulla	0
and	0
its	0
levels	0
in	0
the	0
blood	0
and	0
an	0
elevation	0
in	0
the	0
plasma	0
potassium	1
level	0
.	0
It	0
is	0
concluded	0
that	0
acute	0
amiloride	1
administration	0
to	0
lithium	1
-	0
treated	0
patients	0
suffering	0
from	0
polydipsia	3
and	0
polyuria	3
might	0
relieve	0
these	0
patients	0
but	0
prolonged	0
amiloride	1
supplementation	0
would	0
result	0
in	0
elevated	0
lithium	1
levels	0
and	0
might	0
be	0
hazardous	0
.	0
Cardiovascular	3
complications	4
associated	0
with	0
terbutaline	1
treatment	0
for	0
preterm	3
labor	4
.	0
Severe	0
cardiovascular	3
complications	4
occurred	0
in	0
eight	0
of	0
160	0
patients	0
treated	0
with	0
terbutaline	1
for	0
preterm	3
labor	4
.	0
Associated	0
corticosteroid	0
therapy	0
and	0
twin	0
gestations	0
appear	0
to	0
be	0
predisposing	0
factors	0
.	0
Potential	0
mechanisms	0
of	0
the	0
pathophysiology	0
are	0
briefly	0
discussed	0
.	0
Toxic	3
hepatitis	4
induced	0
by	0
antithyroid	0
drugs	0
:	0
four	0
cases	0
including	0
one	0
with	0
cross	0
-	0
reactivity	0
between	0
carbimazole	1
and	0
benzylthiouracil	1
.	0
0BJECTIVE	0
:	0
This	0
study	0
was	0
conducted	0
to	0
assess	0
the	0
occurrence	0
of	0
hepatic	3
adverse	4
effects	4
encountered	0
with	0
antithyroid	0
drugs	0
.	0
METH0DS	0
:	0
Retrospective	0
review	0
of	0
medical	0
records	0
of	0
236	0
patients	0
with	0
hyperthyroidism	3
admitted	0
in	0
our	0
department	0
(	0
in	0
-	0
or	0
out	0
-	0
patients	0
)	0
from	0
1986	0
to	0
1992	0
.	0
RESULTS	0
:	0
Four	0
patients	0
(	0
1	0
.	0
7	0
%	0
)	0
were	0
identified	0
with	0
toxic	3
hepatitis	4
which	0
could	0
reasonably	0
be	0
attributed	0
to	0
the	0
use	0
of	0
antithyroid	0
agent	0
.	0
Two	0
patients	0
had	0
a	0
cholestatic	3
hepatitis	4
induced	0
by	0
carbimazole	1
(	0
N	1
omercazole	2
)	0
.	0
Two	0
others	0
had	0
a	0
mixed	0
(	0
cholestatic	3
and	0
cytolytic	0
)	0
hepatitis	3
following	0
carbimazole	1
.	0
0ne	0
of	0
the	0
latter	0
two	0
patients	0
further	0
experienced	0
a	0
cytolytic	0
hepatitis	3
which	0
appeared	0
after	0
Benzylthiouracil	1
(	0
Basd	1
ne	2
)	0
had	0
replaced	0
carbimazole	1
.	0
Biological	0
features	0
of	0
hepatitis	3
disappeared	0
in	0
all	0
cases	0
after	0
cessation	0
of	0
the	0
incriminated	0
drug	0
","	0
while	0
biliary	0
","	0
viral	0
and	0
immunological	0
searches	0
were	0
negative	0
.	0
0nly	0
2	0
patients	0
of	0
our	0
retrospective	0
study	0
experienced	0
a	0
mild	0
or	0
severe	0
neutropenia	3
.	0
C0NCLUSI0N	0
:	0
Toxic	3
hepatitis	4
is	0
a	0
potential	0
adverse	0
effect	0
of	0
antithyroid	0
drugs	0
which	0
warrants	0
","	0
as	0
for	0
haematological	0
disturbances	0
","	0
a	0
pre	0
-	0
therapeutic	0
determination	0
and	0
a	0
careful	0
follow	0
-	0
up	0
of	0
relevant	0
biological	0
markers	0
.	0
Moreover	0
","	0
hepatotoxicity	3
may	0
not	0
be	0
restricted	0
to	0
one	0
class	0
of	0
antithyroid	0
agents	0
.	0
Interactive	0
effects	0
of	0
variations	0
in	0
[	0
Na	1
]	0
o	0
and	0
[	0
Ca	1
]	0
o	0
on	0
rat	0
atrial	0
spontaneous	0
frequency	0
.	0
The	0
effects	0
of	0
varying	0
the	0
extracellular	0
concentrations	0
of	0
Na	1
and	0
Ca	1
(	0
[	0
Na	1
]	0
o	0
and	0
[	0
Ca	1
]	0
o	0
)	0
on	0
both	0
","	0
the	0
spontaneous	0
beating	0
and	0
the	0
negative	0
chronotropic	0
action	0
of	0
verapamil	1
","	0
were	0
studied	0
in	0
the	0
isolated	0
rat	0
atria	0
.	0
Basal	0
frequency	0
(	0
BF	0
)	0
evaluated	0
by	0
surface	0
electrogram	0
was	0
223	0
+	0
/	0
-	0
4	0
beats	0
/	0
min	0
.	0
in	0
control	0
Krebs	0
-	0
Ringer	0
containing	0
137	0
mM	0
Na	1
and	0
1	0
.	0
35	0
mM	0
Ca	1
(	0
N	0
)	0
.	0
It	0
decreased	0
by	0
16	0
+	0
/	0
-	0
3	0
%	0
by	0
lowering	0
[	0
Na	1
]	0
o	0
to	0
78	0
mM	0
(	0
LNa	0
)	0
","	0
23	0
+	0
/	0
-	0
2	0
%	0
by	0
lowering	0
simultaneously	0
[	0
Na	1
]	0
o	0
to	0
78	0
mM	0
and	0
[	0
Ca	1
]	0
o	0
to	0
0	0
.	0
675	0
mM	0
(	0
LNa	0
+	0
LCa	0
)	0
and	0
31	0
+	0
/	0
-	0
5	0
%	0
by	0
lowering	0
[	0
Na	1
]	0
o	0
to	0
78	0
mM	0
plus	0
increasing	0
[	0
Ca	1
]	0
o	0
to	0
3	0
.	0
6	0
mM	0
(	0
LNa	0
+	0
HCa	0
)	0
.	0
At	0
normal	0
[	0
Na	1
]	0
o	0
","	0
decrease	0
(	0
0	0
.	0
675	0
mM	0
)	0
or	0
increase	0
(	0
3	0
.	0
6	0
mM	0
)	0
of	0
[	0
Ca	1
]	0
o	0
did	0
not	0
modify	0
BF	0
;	0
a	0
reduction	0
of	0
ten	0
times	0
(	0
0	0
.	0
135	0
mM	0
of	0
normal	0
[	0
Ca	1
]	0
o	0
was	0
effective	0
to	0
reduce	0
BF	0
by	0
40	0
+	0
/	0
-	0
13	0
%	0
.	0
All	0
negative	0
chronotropic	0
effects	0
were	0
BF	0
-	0
dependent	0
.	0
Dose	0
-	0
dependent	0
bradycardia	3
induced	0
by	0
verapamil	1
was	0
potentiated	0
by	0
LNa	0
","	0
LCa	0
","	0
and	0
HCa	0
.	0
Independent	0
but	0
not	0
additive	0
effects	0
of	0
Na	1
and	0
Ca	1
are	0
shown	0
by	0
decreases	0
in	0
the	0
values	0
of	0
[	0
verapamil	1
]	0
o	0
needed	0
to	0
reduce	0
BF	0
by	0
30	0
%	0
(	0
IC30	0
)	0
with	0
the	0
following	0
order	0
of	0
inhibitory	0
potency	0
:	0
LNa	0
>	0
LCa	0
>	0
HCa	0
>	0
N	0
","	0
resulting	0
LNa	0
+	0
HCa	0
similar	0
to	0
LNa	0
.	0
The	0
[	0
verapamil	1
]	0
o	0
that	0
arrested	0
atrial	0
beating	0
(	0
AC	0
)	0
was	0
also	0
potentiated	0
with	0
the	0
order	0
LNa	0
=	0
LNa	0
+	0
LCa	0
=	0
LNa	0
+	0
HCa	0
=	0
LCa	0
>	0
HCa	0
=	0
N	0
.	0
The	0
results	0
indicate	0
that	0
rat	0
atrial	0
spontaneous	0
beating	0
is	0
more	0
dependent	0
on	0
[	0
Na	1
]	0
o	0
than	0
on	0
[	0
Ca	1
]	0
o	0
in	0
a	0
range	0
of	0
+	0
/	0
-	0
50	0
%	0
of	0
their	0
normal	0
concentration	0
.	0
Also	0
the	0
enhancement	0
of	0
verapamil	1
effects	0
on	0
atrial	0
beating	0
was	0
more	0
pronounced	0
at	0
LNa	0
than	0
at	0
LCa	0
.	0
(	0
ABSTRACT	0
TRUNCATED	0
AT	0
250	0
W0RDS	0
)	0
Pseudo	0
-	0
allergic	3
reactions	4
to	0
corticosteroids	1
:	0
diagnosis	0
and	0
alternatives	0
.	0
Two	0
patients	0
treated	0
with	0
parenteral	0
paramethasone	1
(	0
Triniol	0
)	0
and	0
dexamethasone	1
(	0
Sedionbel	0
)	0
are	0
described	0
.	0
A	0
few	0
minutes	0
after	0
administration	0
of	0
the	0
drugs	0
","	0
they	0
presented	0
urticaria	3
(	0
patients	0
1	0
and	0
2	0
)	0
and	0
conjunctivitis	3
(	0
patient	0
1	0
)	0
.	0
The	0
purpose	0
of	0
our	0
study	0
was	0
to	0
determine	0
the	0
cause	0
of	0
the	0
patients	0
'	0
reactions	0
","	0
the	0
immunological	0
mechanisms	0
involved	0
and	0
whether	0
these	0
patients	0
would	0
be	0
able	0
to	0
tolerate	0
any	0
kind	0
of	0
corticoid	0
.	0
Clinical	0
examinations	0
and	0
skin	0
","	0
oral	0
and	0
parenteral	0
challenges	0
with	0
different	0
corticosteroids	1
and	0
ELISA	0
tests	0
were	0
performed	0
.	0
In	0
the	0
two	0
patients	0
","	0
skin	0
and	0
ELISA	0
tests	0
with	0
paramethasone	1
were	0
negative	0
","	0
as	0
was	0
the	0
prick	0
test	0
with	0
each	0
of	0
its	0
excipients	0
.	0
A	0
single	0
-	0
blind	0
parenteral	0
challenge	0
with	0
Triniol	0
was	0
positive	0
in	0
both	0
patients	0
after	0
the	0
administration	0
of	0
1	0
ml	0
of	0
the	0
drug	0
","	0
and	0
negative	0
with	0
its	0
excipients	0
.	0
We	0
also	0
carried	0
out	0
oral	0
and	0
parenteral	0
challenges	0
with	0
other	0
corticosteroids	1
and	0
found	0
intolerance	0
to	0
some	0
of	0
them	0
.	0
These	0
results	0
suggest	0
that	0
paramethasone	1
caused	0
pseudoallergic	0
reactions	0
in	0
our	0
patients	0
.	0
Corticosteroids	0
different	0
from	0
paramethasone	1
also	0
produced	0
hypersensitivity	3
reactions	0
in	0
these	0
patients	0
;	0
however	0
","	0
a	0
few	0
of	0
them	0
were	0
tolerated	0
.	0
The	0
basic	0
mechanisms	0
of	0
those	0
reactions	0
are	0
not	0
yet	0
fully	0
understood	0
.	0
To	0
our	0
knowledge	0
","	0
this	0
is	0
the	0
first	0
report	0
of	0
a	0
pseudo	0
-	0
allergy	3
caused	0
by	0
paramethasone	1
.	0
Study	0
of	0
the	0
role	0
of	0
vitamin	1
B12	2
and	0
folinic	1
acid	2
supplementation	0
in	0
preventing	0
hematologic	0
toxicity	3
of	0
zidovudine	1
.	0
A	0
prospective	0
","	0
randomized	0
study	0
was	0
conducted	0
to	0
evaluate	0
the	0
role	0
of	0
vitamin	1
B12	2
and	0
folinic	1
acid	2
supplementation	0
in	0
preventing	0
zidovudine	1
(	0
ZDV	1
)	0
-	0
induced	0
bone	3
marrow	4
suppression	4
.	0
Seventy	0
-	0
five	0
human	3
immunodeficiency	4
virus	4
(	4
HIV	4
)	4
-	4
infected	4
patients	0
with	0
CD4	0
+	0
cell	0
counts	0
<	0
500	0
/	0
mm3	0
were	0
randomized	0
to	0
receive	0
either	0
ZDV	1
(	0
500	0
mg	0
daily	0
)	0
alone	0
(	0
group	0
I	0
","	0
n	0
=	0
38	0
)	0
or	0
in	0
combination	0
with	0
folinic	1
acid	2
(	0
15	0
mg	0
daily	0
)	0
and	0
intramascular	0
vitamin	1
B12	2
(	0
1000	0
micrograms	0
monthly	0
)	0
(	0
group	0
II	0
","	0
n	0
=	0
37	0
)	0
.	0
Finally	0
","	0
15	0
patients	0
were	0
excluded	0
from	0
the	0
study	0
(	0
noncompliance	0
14	0
","	0
death	3
1	0
)	0
;	0
thus	0
","	0
60	0
patients	0
(	0
31	0
in	0
group	0
I	0
and	0
29	0
in	0
group	0
II	0
)	0
were	0
eligible	0
for	0
analysis	0
.	0
No	0
significant	0
differences	0
between	0
groups	0
were	0
found	0
at	0
enrollment	0
.	0
During	0
the	0
study	0
","	0
vitamin	1
B12	2
and	0
folate	1
levels	0
were	0
significantly	0
higher	0
in	0
group	0
II	0
patients	0
;	0
however	0
","	0
no	0
differences	0
in	0
hemoglobin	0
","	0
hematocrit	0
","	0
mean	0
corpuscular	0
volume	0
","	0
and	0
white	0
-	0
cell	0
","	0
neutrophil	0
and	0
platelet	0
counts	0
were	0
observed	0
between	0
groups	0
at	0
3	0
","	0
6	0
","	0
9	0
and	0
12	0
months	0
.	0
Severe	0
hematologic	0
toxicity	3
(	0
neutrophil	0
count	0
<	0
1000	0
/	0
mm3	0
and	0
/	0
or	0
hemoglobin	0
<	0
8	0
g	0
/	0
dl	0
)	0
occurred	0
in	0
4	0
patients	0
assigned	0
to	0
group	0
I	0
and	0
7	0
assigned	0
to	0
group	0
II	0
.	0
There	0
was	0
no	0
correlation	0
between	0
vitamin	1
B12	2
or	0
folate	1
levels	0
and	0
development	0
of	0
myelosuppression	3
.	0
Vitamin	1
B12	2
and	0
folinic	1
acid	2
supplementation	0
of	0
ZDV	1
therapy	0
does	0
not	0
seem	0
useful	0
in	0
preventing	0
or	0
reducing	0
ZDV	1
-	0
induced	0
myelotoxicity	3
in	0
the	0
overall	0
treated	0
population	0
","	0
although	0
a	0
beneficial	0
effect	0
in	0
certain	0
subgroups	0
of	0
patients	0
cannot	0
be	0
excluded	0
.	0
Safety	0
and	0
side	0
-	0
effects	0
of	0
alprazolam	1
.	0
Controlled	0
study	0
in	0
agoraphobia	3
with	0
panic	3
disorder	4
.	0
BACKGR0UND	0
:	0
The	0
widespread	0
use	0
of	0
benzodiazepines	1
has	0
led	0
to	0
increasing	0
recognition	0
of	0
their	0
unwanted	0
effects	0
.	0
The	0
efficacy	0
of	0
alprazolam	1
and	0
placebo	0
in	0
panic	3
disorder	4
with	0
agoraphobia	3
","	0
and	0
the	0
side	0
-	0
effect	0
and	0
adverse	0
effect	0
profiles	0
of	0
both	0
drug	0
groups	0
were	0
measured	0
.	0
METH0D	0
:	0
In	0
London	0
and	0
Toronto	0
154	0
patients	0
who	0
met	0
DSM	0
-	0
III	0
criteria	0
for	0
panic	3
disorder	4
with	0
agoraphobia	3
were	0
randomised	0
to	0
alprazolam	1
or	0
placebo	0
.	0
Subjects	0
in	0
each	0
drug	0
group	0
also	0
received	0
either	0
exposure	0
or	0
relaxation	0
.	0
Treatment	0
was	0
from	0
weeks	0
0	0
to	0
8	0
and	0
was	0
then	0
tapered	0
from	0
weeks	0
8	0
to	0
16	0
.	0
RESULTS	0
:	0
Mean	0
alprazolam	1
dose	0
was	0
5	0
mg	0
daily	0
.	0
Compared	0
with	0
placebo	0
subjects	0
","	0
alprazolam	1
patients	0
developed	0
more	0
adverse	0
reactions	0
(	0
21	0
%	0
v	0
.	0
0	0
%	0
)	0
of	0
depression	3
","	0
enuresis	3
","	0
disinhibition	0
and	0
aggression	3
;	0
and	0
more	0
side	0
-	0
effects	0
","	0
particularly	0
sedation	0
","	0
irritability	3
","	0
impaired	3
memory	4
","	0
weight	3
loss	4
and	0
ataxia	3
.	0
Side	0
-	0
effects	0
tended	0
to	0
diminish	0
during	0
treatment	0
but	0
remained	0
significant	0
at	0
week	0
8	0
.	0
Despite	0
this	0
","	0
the	0
drop	0
-	0
out	0
rate	0
was	0
low	0
.	0
C0NCLUSI0NS	0
:	0
Alprazolam	1
caused	0
side	0
-	0
effects	0
and	0
adverse	0
effects	0
during	0
treatment	0
but	0
many	0
patients	0
were	0
willing	0
to	0
accept	0
these	0
.	0
Crescentic	0
fibrillary	0
glomerulonephritis	3
associated	0
with	0
intermittent	0
rifampin	1
therapy	0
for	0
pulmonary	3
tuberculosis	4
.	0
This	0
case	0
study	0
reveals	0
an	0
unusual	0
finding	0
of	0
rapidly	0
proliferative	0
crescentic	0
glomerulonephritis	3
in	0
a	0
patient	0
treated	0
with	0
rifampin	1
who	0
had	0
no	0
other	0
identifiable	0
causes	0
for	0
developing	0
this	0
disease	0
.	0
This	0
patient	0
underwent	0
a	0
10	0
-	0
month	0
regimen	0
of	0
rifampin	1
and	0
isoniazid	1
for	0
pulmonary	3
tuberculosis	4
and	0
was	0
discovered	0
to	0
have	0
developed	0
signs	0
of	0
severe	0
renal	3
failure	4
five	0
weeks	0
after	0
completion	0
of	0
therapy	0
.	0
Renal	0
biopsy	0
revealed	0
severe	0
glomerulonephritis	3
with	0
crescents	0
","	0
electron	0
dense	0
fibrillar	0
deposits	0
and	0
moderate	0
lymphocytic	0
interstitial	0
infiltrate	0
.	0
0ther	0
possible	0
causes	0
of	0
rapidly	0
progressive	0
glomerulonephritis	3
were	0
investigated	0
and	0
ruled	0
out	0
.	0
This	0
report	0
documents	0
the	0
unusual	0
occurrence	0
of	0
rapidly	0
progressive	0
glomerulonephritis	3
with	0
crescents	0
and	0
fibrillar	0
glomerulonephritis	3
in	0
a	0
patient	0
treated	0
with	0
rifampin	1
.	0
Acute	0
confusion	3
induced	0
by	0
a	0
high	0
-	0
dose	0
infusion	0
of	0
5	1
-	2
fluorouracil	2
and	0
folinic	1
acid	2
.	0
A	0
61	0
-	0
year	0
-	0
old	0
man	0
was	0
treated	0
with	0
combination	0
chemotherapy	0
incorporating	0
cisplatinum	1
","	0
etoposide	1
","	0
high	0
-	0
dose	0
5	1
-	2
fluorouracil	2
(	0
2	0
","	0
250	0
mg	0
/	0
m2	0
/	0
24	0
hours	0
)	0
and	0
folinic	1
acid	2
for	0
an	0
inoperable	0
gastric	3
adenocarcinoma	4
.	0
He	0
developed	0
acute	0
neurologic	0
symptoms	0
of	0
mental	0
confusion	3
","	0
disorientation	3
and	0
irritability	3
","	0
and	0
then	0
lapsed	0
into	0
a	0
deep	0
coma	3
","	0
lasting	0
for	0
approximately	0
40	0
hours	0
during	0
the	0
first	0
dose	0
(	0
day	0
2	0
)	0
of	0
5	1
-	2
fluorouracil	2
and	0
folinic	1
acid	2
infusion	0
.	0
This	0
complication	0
reappeared	0
on	0
day	0
25	0
during	0
the	0
second	0
dose	0
of	0
5	1
-	2
fluorouracil	2
and	0
folinic	1
acid	2
","	0
which	0
were	0
then	0
the	0
only	0
drugs	0
given	0
.	0
Because	0
folinic	1
acid	2
was	0
unlikely	0
to	0
be	0
associated	0
with	0
this	0
condition	0
","	0
neurotoxicity	3
due	0
to	0
high	0
-	0
dose	0
5	1
-	2
fluorouracil	2
was	0
highly	0
suspected	0
.	0
The	0
pathogenesis	0
of	0
5	1
-	2
fluorouracil	2
neurotoxicity	3
may	0
be	0
due	0
to	0
a	0
Krebs	0
cycle	0
blockade	0
by	0
fluoroacetate	1
and	0
fluorocitrate	1
","	0
thiamine	1
deficiency	0
","	0
or	0
dihydrouracil	1
dehydrogenase	0
deficiency	0
.	0
High	0
-	0
dose	0
5	1
-	2
fluorouracil	2
/	0
folinic	1
acid	2
infusion	0
therapy	0
has	0
recently	0
become	0
a	0
popular	0
regimen	0
for	0
various	0
cancers	3
.	0
It	0
is	0
necessary	0
that	0
both	0
oncologists	0
and	0
neurologists	0
be	0
fully	0
aware	0
of	0
this	0
unusual	0
complication	0
.	0
Effect	0
of	0
switching	0
carbamazepine	1
to	0
oxcarbazepine	1
on	0
the	0
plasma	0
levels	0
of	0
neuroleptics	0
.	0
A	0
case	0
report	0
.	0
Carbamazepine	1
was	0
switched	0
to	0
its	0
10	0
-	0
keto	0
analogue	0
oxcarbazepine	1
among	0
six	0
difficult	0
-	0
to	0
-	0
treat	0
schizophrenic	3
or	0
organic	3
psychotic	4
patients	0
using	0
concomitantly	0
haloperidol	1
","	0
chlorpromazine	1
or	0
clozapine	1
.	0
This	0
change	0
resulted	0
within	0
2	0
-	0
4	0
weeks	0
in	0
the	0
50	0
-	0
200	0
%	0
increase	0
in	0
the	0
plasma	0
levels	0
of	0
these	0
neuroleptics	0
and	0
the	0
appearance	0
of	0
extrapyramidal	3
symptoms	4
.	0
None	0
of	0
the	0
patients	0
showed	0
any	0
clinical	0
deteriotation	0
during	0
the	0
following	0
3	0
-	0
6	0
months	0
.	0
The	0
results	0
of	0
this	0
case	0
report	0
support	0
the	0
idea	0
that	0
in	0
contrast	0
with	0
carbamazepine	1
oxcarbazepine	1
does	0
not	0
induce	0
the	0
hepatic	0
microsomal	0
enzyme	0
systems	0
regulating	0
the	0
inactivation	0
of	0
antipsychotic	0
drugs	0
.	0
Time	0
course	0
of	0
lipid	0
peroxidation	0
in	0
puromycin	1
aminonucleoside	2
-	0
induced	0
nephropathy	3
.	0
Reactive	0
oxygen	1
species	0
have	0
been	0
implicated	0
in	0
the	0
pathogenesis	0
of	0
acute	0
puromycin	1
aminonucleoside	2
(	0
PAN	1
)	0
-	0
induced	0
nephropathy	3
","	0
with	0
antioxidants	0
significantly	0
reducing	0
the	0
proteinuria	3
.	0
The	0
temporal	0
relationship	0
between	0
lipid	0
peroxidation	0
in	0
the	0
kidney	0
and	0
proteinuria	3
was	0
examined	0
in	0
this	0
study	0
.	0
Rats	0
were	0
treated	0
with	0
a	0
single	0
IV	0
injection	0
of	0
puromycin	1
aminonucleoside	2
","	0
(	0
PAN	1
","	0
7	0
.	0
5	0
mg	0
/	0
kg	0
)	0
and	0
24	0
hour	0
urine	0
samples	0
were	0
obtained	0
prior	0
to	0
sacrifice	0
on	0
days	0
3	0
","	0
5	0
","	0
7	0
","	0
10	0
","	0
17	0
","	0
27	0
","	0
41	0
(	0
N	0
=	0
5	0
-	0
10	0
per	0
group	0
)	0
.	0
The	0
kidneys	0
were	0
removed	0
","	0
flushed	0
with	0
ice	0
cold	0
TRIS	0
buffer	0
.	0
Kidney	0
cortices	0
from	0
each	0
animal	0
were	0
used	0
to	0
prepare	0
homogenates	0
.	0
Tissue	0
lipid	0
peroxidation	0
was	0
measured	0
in	0
whole	0
homogenates	0
as	0
well	0
as	0
in	0
lipid	0
extracts	0
from	0
homogenates	0
as	0
thiobarbituric	1
acid	2
reactive	0
substances	0
.	0
Proteinuria	3
was	0
evident	0
at	0
day	0
5	0
","	0
peaked	0
at	0
day	0
7	0
and	0
persisted	0
to	0
day	0
27	0
.	0
Lipid	0
peroxidation	0
in	0
homogenates	0
was	0
maximal	0
at	0
day	0
3	0
and	0
declined	0
rapidly	0
to	0
control	0
levels	0
by	0
day	0
17	0
.	0
This	0
study	0
supports	0
the	0
role	0
of	0
lipid	0
peroxidation	0
in	0
mediating	0
the	0
proteinuric	3
injury	4
in	0
PAN	1
nephropathy	3
.	0
Composition	0
of	0
gall	3
bladder	4
stones	4
associated	0
with	0
octreotide	1
:	0
response	0
to	0
oral	0
ursodeoxycholic	1
acid	2
.	0
0ctreotide	1
","	0
an	0
effective	0
treatment	0
for	0
acromegaly	3
","	0
induces	0
gall	3
bladder	4
stones	4
in	0
13	0
-	0
60	0
%	0
of	0
patients	0
.	0
Because	0
knowledge	0
of	0
stone	0
composition	0
is	0
essential	0
for	0
studies	0
of	0
their	0
pathogenesis	0
","	0
treatment	0
","	0
and	0
prevention	0
","	0
this	0
was	0
investigated	0
by	0
direct	0
and	0
indirect	0
methods	0
in	0
14	0
octreotide	1
treated	0
acromegalic	3
patients	0
with	0
gall	3
stones	4
.	0
Chemical	0
analysis	0
of	0
gall	3
stones	4
retrieved	0
at	0
cholecystectomy	0
from	0
two	0
patients	0
","	0
showed	0
that	0
they	0
contained	0
71	0
%	0
and	0
87	0
%	0
cholesterol	1
by	0
weight	0
.	0
In	0
the	0
remaining	0
12	0
patients	0
","	0
localised	0
computed	0
tomography	0
of	0
the	0
gall	0
bladder	0
showed	0
that	0
eight	0
had	0
stones	0
with	0
maximum	0
attenuation	0
scores	0
of	0
<	0
100	0
Hounsfield	0
units	0
(	0
values	0
of	0
<	0
100	0
HU	0
predict	0
cholesterol	1
rich	0
","	0
dissolvable	0
stones	0
)	0
.	0
Gall	0
bladder	0
bile	0
was	0
obtained	0
by	0
ultrasound	0
guided	0
","	0
fine	0
needle	0
puncture	0
from	0
six	0
patients	0
.	0
All	0
six	0
patients	0
had	0
supersaturated	0
bile	0
(	0
mean	0
(	0
SEM	0
)	0
cholesterol	1
saturation	0
index	0
of	0
1	0
.	0
19	0
(	0
0	0
.	0
8	0
)	0
(	0
range	0
1	0
.	0
1	0
-	0
1	0
.	0
53	0
)	0
)	0
and	0
all	0
had	0
abnormally	0
rapid	0
cholesterol	1
microcrystal	0
nucleation	0
times	0
(	0
<	0
4	0
days	0
(	0
range	0
1	0
-	0
4	0
)	0
)	0
","	0
whilst	0
in	0
four	0
","	0
the	0
bile	0
contained	0
cholesterol	1
microcrystals	0
immediately	0
after	0
sampling	0
.	0
0f	0
the	0
12	0
patients	0
considered	0
for	0
oral	0
ursodeoxycholic	1
acid	2
(	0
UDCA	1
)	0
treatment	0
","	0
two	0
had	0
a	0
blocked	0
cystic	0
duct	0
and	0
were	0
not	0
started	0
on	0
UDCA	1
while	0
one	0
was	0
lost	0
to	0
follow	0
up	0
.	0
After	0
one	0
year	0
of	0
treatment	0
","	0
five	0
of	0
the	0
remaining	0
nine	0
patients	0
showed	0
either	0
partial	0
(	0
n	0
=	0
3	0
)	0
or	0
complete	0
(	0
n	0
=	0
2	0
)	0
gall	3
stone	4
dissolution	0
","	0
suggesting	0
that	0
their	0
stones	0
were	0
cholesterol	1
rich	0
.	0
This	0
corresponds	0
","	0
by	0
actuarial	0
(	0
life	0
table	0
)	0
analysis	0
","	0
to	0
a	0
combined	0
gall	3
stone	4
dissolution	0
rate	0
of	0
58	0
.	0
3	0
(	0
15	0
.	0
9	0
%	0
)	0
.	0
In	0
conclusion	0
","	0
octreotide	1
induced	0
gall	3
stones	4
are	0
generally	0
small	0
","	0
multiple	0
","	0
and	0
cholesterol	1
rich	0
although	0
","	0
in	0
common	0
with	0
spontaneous	0
gall	3
stone	4
disease	4
","	0
at	0
presentation	0
some	0
patients	0
will	0
have	0
a	0
blocked	0
cystic	0
duct	0
and	0
some	0
gall	3
stones	4
containing	0
calcium	1
.	0
Erythema	3
multiforme	4
and	0
hypersensitivity	3
myocarditis	4
caused	0
by	0
ampicillin	1
.	0
0BJECTIVE	0
:	0
To	0
report	0
a	0
case	0
of	0
erythema	3
multiforme	4
and	0
hypersensitivity	3
myocarditis	4
caused	0
by	0
ampicillin	1
.	0
CASE	0
SUMMARY	0
:	0
A	0
13	0
-	0
year	0
-	0
old	0
boy	0
was	0
treated	0
with	0
ampicillin	1
and	0
gentamicin	1
because	0
of	0
suspected	0
septicemia	3
.	0
Medications	0
were	0
discontinued	0
when	0
erythema	3
multiforme	4
and	0
congestive	3
heart	4
failure	4
caused	0
by	0
myocarditis	3
occurred	0
.	0
The	0
patient	0
was	0
treated	0
with	0
methylprednisolone	1
and	0
gradually	0
improved	0
.	0
Macrophage	0
-	0
migration	0
inhibition	0
(	0
MIF	0
)	0
test	0
with	0
ampicillin	1
was	0
positive	0
.	0
DISCUSSI0N	0
:	0
After	0
most	0
infections	3
causing	0
erythema	3
multiforme	4
and	0
myocarditis	3
were	0
ruled	0
out	0
","	0
a	0
drug	3
-	4
induced	4
allergic	4
reaction	4
was	0
suspected	0
.	0
Positive	0
MIF	0
test	0
for	0
ampicillin	1
showed	0
sensitization	0
of	0
the	0
patient	0
'	0
s	0
lymphocytes	0
to	0
ampicillin	1
.	0
C0NCLUSI0NS	0
:	0
Hypersensitivity	3
myocarditis	4
is	0
a	0
rare	0
and	0
dangerous	0
manifestation	0
of	0
allergy	3
to	0
penicillins	1
.	0
Clomipramine	1
-	0
induced	0
sleep	3
disturbance	4
does	0
not	0
impair	0
its	0
prolactin	0
-	0
releasing	0
action	0
.	0
The	0
present	0
study	0
was	0
undertaken	0
to	0
examine	0
the	0
role	0
of	0
sleep	3
disturbance	4
","	0
induced	0
by	0
clomipramine	1
administration	0
","	0
on	0
the	0
secretory	0
rate	0
of	0
prolactin	0
(	0
PRL	0
)	0
in	0
addition	0
to	0
the	0
direct	0
drug	0
effect	0
.	0
Two	0
groups	0
of	0
supine	0
subjects	0
were	0
studied	0
under	0
placebo	0
-	0
controlled	0
conditions	0
","	0
one	0
during	0
the	0
night	0
","	0
when	0
sleeping	0
(	0
n	0
=	0
7	0
)	0
and	0
the	0
other	0
at	0
daytime	0
","	0
when	0
awake	0
(	0
n	0
=	0
6	0
)	0
.	0
Each	0
subject	0
received	0
a	0
single	0
50	0
mg	0
dose	0
of	0
clomipramine	1
given	0
orally	0
2	0
hours	0
before	0
blood	0
collection	0
.	0
Plasma	0
PRL	0
concentrations	0
were	0
analysed	0
at	0
10	0
min	0
intervals	0
and	0
underlying	0
secretory	0
rates	0
calculated	0
by	0
a	0
deconvolution	0
procedure	0
.	0
For	0
both	0
experiments	0
the	0
drug	0
intake	0
led	0
to	0
significant	0
increases	0
in	0
PRL	0
secretion	0
","	0
acting	0
preferentially	0
on	0
tonic	0
secretion	0
as	0
pulse	0
amplitude	0
and	0
frequency	0
did	0
not	0
differ	0
significantly	0
from	0
corresponding	0
control	0
values	0
.	0
During	0
the	0
night	0
clomipramine	1
ingestion	0
altered	0
the	0
complete	0
sleep	0
architecture	0
in	0
that	0
it	0
suppressed	0
REM	0
sleep	0
and	0
the	0
sleep	0
cycles	0
and	0
induced	0
increased	0
wakefulness	0
.	0
As	0
the	0
relative	0
increase	0
in	0
PRL	0
secretion	0
expressed	0
as	0
a	0
percentage	0
of	0
the	0
mean	0
did	0
not	0
significantly	0
differ	0
between	0
the	0
night	0
and	0
day	0
time	0
studies	0
(	0
46	0
+	0
/	0
-	0
19	0
%	0
vs	0
34	0
+	0
/	0
-	0
10	0
%	0
)	0
","	0
it	0
can	0
be	0
concluded	0
that	0
the	0
observed	0
sleep	3
disturbance	4
did	0
not	0
interfere	0
with	0
the	0
drug	0
action	0
per	0
se	0
.	0
The	0
presence	0
of	0
REM	0
sleep	0
was	0
shown	0
not	0
to	0
be	0
a	0
determining	0
factor	0
either	0
for	0
secretory	0
pulse	0
amplitude	0
and	0
frequency	0
","	0
as	0
","	0
for	0
both	0
","	0
mean	0
nocturnal	0
values	0
were	0
similar	0
with	0
and	0
without	0
prior	0
clomipramine	1
ingestion	0
.	0
Survey	0
of	0
complications	0
of	0
indocyanine	1
green	2
angiography	0
in	0
Japan	0
.	0
PURP0SE	0
:	0
We	0
evaluated	0
the	0
safety	0
of	0
indocyanine	1
green	2
for	0
use	0
in	0
fundus	0
angiography	0
.	0
METH0DS	0
:	0
We	0
sent	0
a	0
questionnaire	0
concerning	0
complications	0
of	0
indocyanine	1
green	2
to	0
32	0
institutions	0
in	0
Japan	0
","	0
which	0
were	0
selected	0
on	0
the	0
basis	0
of	0
the	0
client	0
list	0
from	0
the	0
Topcon	0
Company	0
","	0
which	0
manufactures	0
the	0
indocyanine	1
green	2
fundus	0
camera	0
.	0
RESULTS	0
:	0
0phthalmologists	0
at	0
15	0
institutions	0
responded	0
","	0
reporting	0
a	0
total	0
of	0
3	0
","	0
774	0
indocyanine	1
green	2
angiograms	0
performed	0
on	0
2	0
","	0
820	0
patients	0
between	0
June	0
1984	0
and	0
September	0
1992	0
.	0
Before	0
angiography	0
","	0
intradermal	0
or	0
intravenous	0
indocyanine	1
green	2
testing	0
","	0
or	0
both	0
was	0
performed	0
at	0
13	0
of	0
15	0
institutions	0
.	0
For	0
three	0
patients	0
","	0
the	0
decision	0
was	0
made	0
not	0
to	0
proceed	0
with	0
angiography	0
after	0
positive	0
preangiographic	0
testing	0
.	0
The	0
dosage	0
of	0
indocyanine	1
green	2
used	0
for	0
angiography	0
varied	0
from	0
25	0
to	0
75	0
mg	0
","	0
depending	0
upon	0
the	0
institution	0
.	0
There	0
were	0
13	0
cases	0
of	0
adverse	0
reactions	0
(	0
0	0
.	0
34	0
%	0
)	0
","	0
ten	0
of	0
which	0
were	0
mild	0
reactions	0
such	0
as	0
nausea	3
","	0
exanthema	3
","	0
urtication	3
","	0
itchiness	3
","	0
and	0
urgency	0
to	0
defecate	0
","	0
and	0
did	0
not	0
require	0
treatment	0
.	0
Also	0
recorded	0
were	0
one	0
case	0
of	0
pain	3
of	0
the	0
vein	0
","	0
which	0
required	0
treatment	0
","	0
and	0
two	0
cases	0
of	0
hypotension	3
.	0
The	0
two	0
hypotensive	3
patients	0
required	0
treatment	0
for	0
shock	3
.	0
C0NCLUSI0NS	0
:	0
A	0
comparison	0
of	0
frequency	0
of	0
adverse	0
reactions	0
to	0
indocyanine	1
green	2
with	0
the	0
previously	0
reported	0
frequency	0
of	0
such	0
reactions	0
to	0
fluorescein	1
sodium	2
indicated	0
that	0
indocyanine	1
green	2
is	0
a	0
safe	0
as	0
fluorescein	1
for	0
use	0
in	0
angiography	0
.	0
Angioedema	3
following	0
the	0
intravenous	0
administration	0
of	0
metoprolol	1
.	0
A	0
72	0
-	0
year	0
-	0
old	0
woman	0
was	0
admitted	0
to	0
the	0
hospital	0
with	0
"	0
flash	0
"	0
pulmonary	3
edema	4
","	0
preceded	0
by	0
chest	3
pain	4
","	0
requiring	0
intubation	0
.	0
Her	0
medical	0
history	0
included	0
coronary	3
artery	4
disease	4
with	0
previous	0
myocardial	3
infarctions	4
","	0
hypertension	3
","	0
and	0
diabetes	3
mellitus	4
.	0
A	0
history	0
of	0
angioedema	3
secondary	0
to	0
lisinopril	1
therapy	0
was	0
elicited	0
.	0
Current	0
medications	0
did	0
not	0
include	0
angiotensin	1
-	0
converting	0
enzyme	0
inhibitors	0
or	0
beta	0
-	0
blockers	0
.	0
She	0
had	0
no	0
previous	0
beta	0
-	0
blocking	0
drug	0
exposure	0
.	0
During	0
the	0
first	0
day	0
of	0
hospitalization	0
(	0
while	0
intubated	0
)	0
","	0
intravenous	0
metoprolol	1
was	0
given	0
","	0
resulting	0
in	0
severe	0
angioedema	3
.	0
The	0
angioedema	3
resolved	0
after	0
therapy	0
with	0
intravenous	0
steroids	1
and	0
diphenhydramine	1
hydrochloride	0
.	0
Effect	0
of	0
coniine	1
on	0
the	0
developing	0
chick	0
embryo	0
.	0
Coniine	1
","	0
an	0
alkaloid	0
from	0
Conium	0
maculatum	0
(	0
poison	0
hemlock	0
)	0
","	0
has	0
been	0
shown	0
to	0
be	0
teratogenic	0
in	0
livestock	0
.	0
The	0
major	0
teratogenic	0
outcome	0
is	0
arthrogryposis	3
","	0
presumably	0
due	0
to	0
nicotinic	0
receptor	0
blockade	0
.	0
However	0
","	0
coniine	1
has	0
failed	0
to	0
produce	0
arthrogryposis	3
in	0
rats	0
or	0
mice	0
and	0
is	0
only	0
weakly	0
teratogenic	0
in	0
rabbits	0
.	0
The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
evaluate	0
and	0
compare	0
the	0
effects	0
of	0
coniine	1
and	0
nicotine	1
in	0
the	0
developing	0
chick	0
.	0
Concentrations	0
of	0
coniine	1
and	0
nicotine	1
sulfate	0
were	0
0	0
.	0
15	0
%	0
","	0
0	0
.	0
3	0
%	0
","	0
0	0
.	0
75	0
%	0
","	0
0	0
.	0
15	0
%	0
","	0
0	0
.	0
75	0
%	0
","	0
1	0
.	0
5	0
%	0
","	0
3	0
%	0
","	0
and	0
6	0
%	0
and	0
1	0
%	0
","	0
5	0
%	0
","	0
and	0
10	0
%	0
","	0
respectively	0
.	0
Both	0
compounds	0
caused	0
deformations	3
and	0
lethality	0
in	0
a	0
dose	0
-	0
dependent	0
manner	0
.	0
All	0
concentrations	0
of	0
nicotine	1
sulfate	0
caused	0
some	0
lethality	0
but	0
a	0
no	0
effect	0
level	0
for	0
coniine	1
lethality	0
was	0
0	0
.	0
75	0
%	0
.	0
The	0
deformations	3
caused	0
by	0
both	0
coniine	1
and	0
nicotine	1
sulfate	0
were	0
excessive	3
flexion	4
or	4
extension	4
of	4
one	4
or	4
more	4
toes	4
.	0
No	0
histopathological	0
alterations	0
or	0
differences	0
in	0
bone	0
formation	0
were	0
seen	0
in	0
the	0
limbs	0
or	0
toes	0
of	0
any	0
chicks	0
from	0
any	0
group	0
;	0
however	0
","	0
extensive	0
cranial	3
hemorrhage	4
occurred	0
in	0
all	0
nicotine	1
sulfate	0
-	0
treated	0
chicks	0
.	0
There	0
was	0
a	0
statistically	0
significant	0
(	0
P	0
<	0
or	0
=	0
0	0
.	0
1	0
)	0
decrease	0
in	0
movement	0
in	0
coniine	1
and	0
nicotine	1
sulfate	0
treated	0
chicks	0
as	0
determined	0
by	0
ultrasound	0
.	0
Control	0
chicks	0
were	0
in	0
motion	0
an	0
average	0
of	0
33	0
.	0
67	0
%	0
of	0
the	0
time	0
","	0
while	0
coniine	1
-	0
treated	0
chicks	0
were	0
only	0
moving	0
8	0
.	0
95	0
%	0
of	0
a	0
5	0
-	0
min	0
interval	0
","	0
and	0
no	0
movement	0
was	0
observed	0
for	0
nicotine	1
sulfate	0
treated	0
chicks	0
.	0
In	0
summary	0
","	0
the	0
chick	0
embryo	0
provides	0
a	0
reliable	0
and	0
simple	0
experimental	0
animal	0
model	0
of	0
coniine	1
-	0
induced	0
arthrogryposis	3
.	0
Data	0
from	0
this	0
model	0
support	0
a	0
mechanism	0
involving	0
nicotinic	0
receptor	0
blockade	0
with	0
subsequent	0
decreased	0
fetal	0
movement	0
.	0
Immediate	0
allergic	3
reactions	4
to	0
amoxicillin	1
.	0
A	0
large	0
group	0
of	0
patients	0
with	0
suspected	0
allergic	3
reactions	4
to	0
beta	1
-	2
lactam	2
antibiotics	0
was	0
evaluated	0
.	0
A	0
detailed	0
clinical	0
history	0
","	0
together	0
with	0
skin	0
tests	0
","	0
RAST	0
(	0
radioallergosorbent	0
test	0
)	0
","	0
and	0
controlled	0
challenge	0
tests	0
","	0
was	0
used	0
to	0
establish	0
whether	0
patients	0
allergic	3
to	0
beta	1
-	2
lactam	2
antibiotics	0
had	0
selective	0
immediate	0
allergic	3
responses	0
to	0
amoxicillin	1
(	0
AX	1
)	0
or	0
were	0
cross	0
-	0
reacting	0
with	0
other	0
penicillin	1
derivatives	0
.	0
Skin	0
tests	0
were	0
performed	0
with	0
benzylpenicilloyl	1
-	2
poly	2
-	2
L	2
-	2
lysine	2
(	0
BP0	1
-	2
PLL	2
)	0
","	0
benzylpenicilloate	1
","	0
benzylpenicillin	1
(	0
PG	1
)	0
","	0
ampicillin	1
(	0
AMP	1
)	0
","	0
and	0
AX	1
.	0
RAST	0
for	0
BP0	1
-	2
PLL	2
and	0
AX	1
-	0
PLL	0
was	0
done	0
.	0
When	0
both	0
skin	0
test	0
and	0
RAST	0
for	0
BP0	1
were	0
negative	0
","	0
single	0
-	0
blind	0
","	0
placebo	0
-	0
controlled	0
challenge	0
tests	0
were	0
done	0
to	0
ensure	0
tolerance	0
of	0
PG	1
or	0
sensitivity	0
to	0
AX	1
.	0
A	0
total	0
of	0
177	0
patients	0
were	0
diagnosed	0
as	0
allergic	3
to	0
beta	1
-	2
lactam	2
antibiotics	0
.	0
We	0
selected	0
the	0
54	0
(	0
30	0
.	0
5	0
%	0
)	0
cases	0
of	0
immediate	0
AX	1
allergy	3
with	0
good	0
tolerance	0
of	0
PG	1
.	0
Anaphylaxis	3
was	0
seen	0
in	0
37	0
patients	0
(	0
69	0
%	0
)	0
","	0
the	0
other	0
17	0
(	0
31	0
%	0
)	0
having	0
urticaria	3
and	0
/	0
or	0
angioedema	3
.	0
All	0
the	0
patients	0
were	0
skin	0
test	0
negative	0
to	0
BP0	1
;	0
49	0
of	0
51	0
(	0
96	0
%	0
)	0
were	0
also	0
negative	0
to	0
MDM	3
","	0
and	0
44	0
of	0
46	0
(	0
96	0
%	0
)	0
to	0
PG	1
.	0
Skin	0
tests	0
with	0
AX	1
were	0
positive	0
in	0
34	0
(	0
63	0
%	0
)	0
patients	0
.	0
RAST	0
was	0
positive	0
for	0
AX	1
in	0
22	0
patients	0
(	0
41	0
%	0
)	0
and	0
to	0
BP0	1
in	0
just	0
5	0
(	0
9	0
%	0
)	0
.	0
None	0
of	0
the	0
sera	0
with	0
negative	0
RAST	0
for	0
AX	1
were	0
positive	0
to	0
BP0	1
.	0
Challenge	0
tests	0
with	0
AX	1
were	0
performed	0
in	0
23	0
subjects	0
(	0
43	0
%	0
)	0
to	0
establish	0
the	0
diagnosis	0
of	0
immediate	0
allergic	3
reaction	4
to	0
AX	1
","	0
and	0
in	0
15	0
cases	0
(	0
28	0
%	0
)	0
both	0
skin	0
test	0
and	0
RAST	0
for	0
AX	1
were	0
negative	0
.	0
PG	1
was	0
well	0
tolerated	0
by	0
all	0
54	0
patients	0
.	0
We	0
describe	0
the	0
largest	0
group	0
of	0
AX	1
-	0
allergic	3
patients	0
who	0
have	0
tolerated	0
PG	1
reported	0
so	0
far	0
.	0
Diagnosis	0
of	0
these	0
patients	0
can	0
be	0
achieved	0
only	0
if	0
specific	0
AX	1
-	0
related	0
reagents	0
are	0
employed	0
.	0
Further	0
studies	0
are	0
necessary	0
to	0
determine	0
the	0
exact	0
extent	0
of	0
this	0
problem	0
and	0
to	0
improve	0
the	0
efficacy	0
of	0
diagnostic	0
methods	0
.	0
Reversal	0
by	0
phenylephrine	1
of	0
the	0
beneficial	0
effects	0
of	0
intravenous	0
nitroglycerin	1
in	0
patients	0
with	0
acute	3
myocardial	4
infarction	4
.	0
Nitroglycerin	1
has	0
been	0
shown	0
to	0
reduce	0
ST	0
-	0
segment	0
elevation	0
during	0
acute	3
myocardial	4
infarction	4
","	0
an	0
effect	0
potentiated	0
in	0
the	0
dog	0
by	0
agents	0
that	0
reverse	0
nitroglycerin	1
-	0
induced	0
hypotension	3
.	0
0ur	0
study	0
was	0
designed	0
to	0
determine	0
the	0
effects	0
of	0
combined	0
nitroglycerin	1
and	0
phenylephrine	1
therapy	0
.	0
Ten	0
patients	0
with	0
acute	0
transmural	0
myocardial	3
infarctions	4
received	0
intravenous	0
nitroglycerin	1
","	0
sufficient	0
to	0
reduce	0
mean	0
arterial	0
pressure	0
from	0
107	0
+	0
/	0
-	0
6	0
to	0
85	0
+	0
/	0
-	0
6	0
mm	0
Hg	0
(	0
P	0
less	0
than	0
0	0
.	0
1	0
)	0
","	0
for	0
60	0
minutes	0
.	0
Left	0
ventricular	0
filling	0
pressure	0
decreased	0
from	0
19	0
+	0
/	0
-	0
2	0
to	0
11	0
+	0
/	0
-	0
2	0
mm	0
Hg	0
(	0
P	0
less	0
than	0
0	0
.	0
1	0
)	0
.	0
SigmaST	0
","	0
the	0
sum	0
of	0
ST	0
-	0
segment	0
elevations	0
in	0
16	0
precordial	0
leads	0
","	0
decreased	0
(	0
P	0
less	0
than	0
0	0
.	0
2	0
)	0
with	0
intravenous	0
nitroglycerin	1
.	0
Subsequent	0
addition	0
of	0
phenylephrine	1
infusion	0
","	0
sufficient	0
to	0
re	0
-	0
elevate	0
mean	0
arterial	0
pressure	0
to	0
106	0
+	0
/	0
-	0
4	0
mm	0
Hg	0
(	0
P	0
less	0
than	0
0	0
.	0
1	0
)	0
for	0
30	0
minutes	0
","	0
increased	0
left	0
ventricular	0
filling	0
pressure	0
to	0
17	0
+	0
/	0
-	0
2	0
mm	0
Hg	0
(	0
P	0
less	0
than	0
0	0
.	0
5	0
)	0
and	0
also	0
significantly	0
increased	0
sigmaST	0
(	0
P	0
less	0
than	0
0	0
.	0
5	0
)	0
.	0
0ur	0
results	0
suggest	0
that	0
addition	0
of	0
phenylephrine	1
to	0
nitroglycerin	1
is	0
not	0
beneficial	0
in	0
the	0
treatment	0
of	0
patients	0
with	0
acute	3
myocardial	4
infarction	4
.	0
Acetazolamide	1
-	0
induced	0
nephrolithiasis	3
:	0
implications	0
for	0
treatment	0
of	0
neuromuscular	3
disorders	4
.	0
Carbonic	0
anhydrase	0
inhibitors	0
can	0
cause	0
nephrolithiasis	3
.	0
We	0
studied	0
20	0
patients	0
receiving	0
long	0
-	0
term	0
carbonic	0
anhydrase	0
inhibitor	0
treatment	0
for	0
periodic	0
paralysis	3
and	0
myotonia	3
.	0
Three	0
patients	0
on	0
acetazolamide	1
(	0
15	0
%	0
)	0
developed	0
renal	3
calculi	4
.	0
Extracorporeal	0
lithotripsy	0
successfully	0
removed	0
a	0
renal	3
calculus	4
in	0
one	0
patient	0
and	0
surgery	0
removed	0
a	0
staghorn	0
calculus	3
in	0
another	0
","	0
permitting	0
continued	0
treatment	0
.	0
Renal	0
function	0
remained	0
normal	0
in	0
all	0
patients	0
.	0
Nephrolithiasis	3
is	0
a	0
complication	0
of	0
acetazolamide	1
but	0
does	0
not	0
preclude	0
its	0
use	0
.	0
Effects	0
of	0
calcium	1
channel	0
blockers	0
on	0
bupivacaine	1
-	0
induced	0
toxicity	3
.	0
The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
investigate	0
the	0
influence	0
of	0
calcium	1
channel	0
blockers	0
on	0
bupivacaine	1
-	0
induced	0
acute	0
toxicity	3
.	0
For	0
each	0
of	0
the	0
three	0
tested	0
calcium	1
channel	0
blockers	0
(	0
diltiazem	1
","	0
verapamil	1
and	0
bepridil	1
)	0
6	0
groups	0
of	0
mice	0
were	0
treated	0
by	0
two	0
different	0
doses	0
","	0
i	0
.	0
e	0
.	0
2	0
and	0
10	0
mg	0
/	0
kg	0
/	0
i	0
.	0
p	0
.	0
","	0
or	0
an	0
equal	0
volume	0
of	0
saline	0
for	0
the	0
control	0
group	0
(	0
n	0
=	0
20	0
)	0
;	0
15	0
minutes	0
later	0
","	0
all	0
the	0
animals	0
were	0
injected	0
with	0
a	0
single	0
50	0
mg	0
/	0
kg	0
/	0
i	0
.	0
p	0
.	0
dose	0
of	0
bupivacaine	1
.	0
The	0
convulsant	0
activity	0
","	0
the	0
time	0
of	0
latency	0
to	0
convulse	0
and	0
the	0
mortality	0
rate	0
were	0
assessed	0
in	0
each	0
group	0
.	0
The	0
local	0
anesthetic	0
-	0
induced	0
mortality	0
was	0
significantly	0
increased	0
by	0
the	0
three	0
different	0
calcium	1
channel	0
blockers	0
.	0
The	0
convulsant	0
activity	0
of	0
bupivacaine	1
was	0
not	0
significantly	0
modified	0
but	0
calcium	1
channel	0
blockers	0
decreased	0
the	0
time	0
of	0
latency	0
to	0
obtain	0
bupivacaine	1
-	0
induced	0
convulsions	3
;	0
this	0
effect	0
was	0
less	0
pronounced	0
with	0
bepridil	1
.	0
Epidural	0
blood	0
flow	0
during	0
prostaglandin	1
E1	2
or	0
trimethaphan	1
induced	0
hypotension	3
.	0
To	0
evaluate	0
the	0
effect	0
of	0
prostaglandin	1
E1	2
(	0
PGE1	1
)	0
or	0
trimethaphan	1
(	0
TMP	1
)	0
induced	0
hypotension	3
on	0
epidural	0
blood	0
flow	0
(	0
EBF	0
)	0
during	0
spinal	0
surgery	0
","	0
EBF	0
was	0
measured	0
using	0
the	0
heat	0
clearance	0
method	0
in	0
30	0
patients	0
who	0
underwent	0
postero	0
-	0
lateral	0
interbody	0
fusion	0
under	0
isoflurane	1
anaesthesia	0
.	0
An	0
initial	0
dose	0
of	0
0	0
.	0
1	0
microgram	0
.	0
kg	0
-	0
1	0
.	0
min	0
-	0
1	0
of	0
PGE1	1
(	0
15	0
patients	0
)	0
","	0
or	0
10	0
micrograms	0
.	0
kg	0
-	0
1	0
.	0
min	0
-	0
1	0
of	0
TMP	1
(	0
15	0
patients	0
)	0
was	0
administered	0
intravenously	0
after	0
the	0
dural	0
opening	0
and	0
the	0
dose	0
was	0
adjusted	0
to	0
maintain	0
the	0
mean	0
arterial	0
blood	0
pressure	0
(	0
MAP	0
)	0
at	0
about	0
60	0
mmHg	0
.	0
The	0
hypotensive	3
drug	0
was	0
discontinued	0
at	0
the	0
completion	0
of	0
the	0
operative	0
procedure	0
.	0
After	0
starting	0
PGE1	1
or	0
TMP	1
","	0
MAP	0
and	0
rate	0
pressure	0
product	0
(	0
RPP	0
)	0
decreased	0
significantly	0
compared	0
with	0
preinfusion	0
values	0
(	0
P	0
<	0
0	0
.	0
1	0
)	0
","	0
and	0
the	0
degree	0
of	0
hypotension	3
due	0
to	0
PGE1	1
remained	0
constant	0
until	0
60	0
min	0
after	0
its	0
discontinuation	0
.	0
Heart	0
rate	0
(	0
HR	0
)	0
did	0
not	0
change	0
in	0
either	0
group	0
.	0
EBFF	0
did	0
not	0
change	0
during	0
PGE1	1
infusion	0
whereas	0
in	0
the	0
TMP	1
group	0
","	0
EBF	0
decreased	0
significantly	0
at	0
30	0
and	0
60	0
min	0
after	0
the	0
start	0
of	0
TMP	1
(	0
preinfusion	0
:	0
45	0
.	0
9	0
+	0
/	0
-	0
13	0
.	0
9	0
ml	0
/	0
100g	0
/	0
min	0
.	0
30	0
min	0
:	0
32	0
.	0
3	0
+	0
/	0
-	0
9	0
.	0
9	0
ml	0
/	0
100	0
g	0
/	0
min	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
60	0
min	0
:	0
30	0
+	0
/	0
-	0
7	0
.	0
5	0
ml	0
/	0
100	0
g	0
/	0
min	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
)	0
.	0
These	0
results	0
suggest	0
that	0
PGE1	1
may	0
be	0
preferable	0
to	0
TMP	1
for	0
hypotensive	3
anaesthesia	0
in	0
spinal	0
surgery	0
because	0
TMP	1
decreased	0
EBF	0
.	0
Dup	1
753	2
prevents	0
the	0
development	0
of	0
puromycin	1
aminonucleoside	2
-	0
induced	0
nephrosis	3
.	0
The	0
appearance	0
of	0
nephrotic	3
syndromes	4
such	0
as	0
proteinuria	3
","	0
hypoalbuminemia	3
","	0
hypercholesterolemia	3
and	0
increase	0
in	0
blood	1
nitrogen	2
urea	2
","	0
induced	0
in	0
rats	0
by	0
injection	0
of	0
puromycin	1
aminonucleoside	2
was	0
markedly	0
inhibited	0
by	0
oral	0
administration	0
of	0
Dup	1
753	2
(	0
losartan	1
)	0
","	0
a	0
novel	0
angiotensin	1
II	2
receptor	0
antagonist	0
","	0
at	0
a	0
dose	0
of	0
1	0
or	0
2	0
mg	0
/	0
kg	0
per	0
day	0
.	0
The	0
results	0
suggest	0
a	0
possible	0
involvement	0
of	0
the	0
renin	0
-	0
angiotensin	1
system	0
in	0
the	0
development	0
of	0
puromycin	1
aminonucleoside	2
-	0
induced	0
nephrosis	3
.	0
Neuroplasticity	0
of	0
the	0
adult	0
primate	0
auditory	0
cortex	0
following	0
cochlear	0
hearing	3
loss	4
.	0
Tonotopic	0
organization	0
is	0
an	0
essential	0
feature	0
of	0
the	0
primary	0
auditory	0
area	0
(	0
A1	0
)	0
of	0
primate	0
cortex	0
.	0
In	0
A1	0
of	0
macaque	0
monkeys	0
","	0
low	0
frequencies	0
are	0
represented	0
rostrolaterally	0
and	0
high	0
frequencies	0
are	0
represented	0
caudomedially	0
.	0
The	0
purpose	0
of	0
this	0
study	0
was	0
to	0
determine	0
if	0
changes	0
occur	0
in	0
this	0
tonotopic	0
organization	0
following	0
cochlear	0
hearing	3
loss	4
.	0
Under	0
anesthesia	0
","	0
the	0
superior	0
temporal	0
gyrus	0
of	0
adult	0
macaque	0
monkeys	0
was	0
exposed	0
","	0
and	0
the	0
tonotopic	0
organization	0
of	0
A1	0
was	0
mapped	0
using	0
conventional	0
microelectrode	0
recording	0
techniques	0
.	0
Following	0
recovery	0
","	0
the	0
monkeys	0
were	0
selectively	0
deafened	0
for	0
high	0
frequencies	0
using	0
kanamycin	1
and	0
furosemide	1
.	0
The	0
actual	0
frequencies	0
deafened	0
were	0
determined	0
by	0
the	0
loss	0
of	0
tone	0
-	0
burst	0
elicited	0
auditory	0
brainstem	0
responses	0
.	0
Three	0
months	0
after	0
deafening	0
","	0
A1	0
was	0
remapped	0
.	0
Postmortem	0
cytoarchitectural	0
features	0
identifying	0
A1	0
were	0
correlated	0
with	0
the	0
electrophysiologic	0
data	0
.	0
The	0
results	0
indicate	0
that	0
the	0
deprived	0
area	0
of	0
A1	0
undergoes	0
extensive	0
reorganization	0
and	0
becomes	0
responsive	0
to	0
intact	0
cochlear	0
frequencies	0
.	0
The	0
region	0
of	0
cortex	0
that	0
represents	0
the	0
low	0
frequencies	0
was	0
not	0
obviously	0
affected	0
by	0
the	0
cochlear	0
hearing	3
loss	4
.	0
Sodium	1
bicarbonate	2
alleviates	0
penile	3
pain	4
induced	0
by	0
intracavernous	0
injections	0
for	0
erectile	3
dysfunction	4
.	0
In	0
an	0
attempt	0
to	0
determine	0
whether	0
penile	3
pain	4
associated	0
with	0
intracorporeal	0
injections	0
could	0
be	0
due	0
to	0
the	0
acidity	0
of	0
the	0
medication	0
","	0
we	0
performed	0
a	0
randomized	0
study	0
comparing	0
the	0
incidence	0
of	0
penile	3
pain	4
following	0
intracorporeal	0
injections	0
with	0
or	0
without	0
the	0
addition	0
of	0
sodium	1
bicarbonate	2
to	0
the	0
intracorporeal	0
medications	0
.	0
A	0
total	0
of	0
38	0
consecutive	0
patients	0
who	0
presented	0
to	0
our	0
clinic	0
with	0
impotence	3
received	0
0	0
.	0
2	0
ml	0
.	0
of	0
a	0
combination	0
of	0
3	0
drugs	0
:	0
6	0
mg	0
.	0
papaverine	1
","	0
100	0
micrograms	0
.	0
phentolamine	1
and	0
10	0
micrograms	0
.	0
prostaglandin	1
E1	2
with	0
(	0
pH	0
7	0
.	0
5	0
)	0
or	0
without	0
(	0
pH	0
4	0
.	0
17	0
)	0
the	0
addition	0
of	0
sodium	1
bicarbonate	2
(	0
0	0
.	0
3	0
mEq	0
.	0
)	0
.	0
0f	0
the	0
19	0
patients	0
without	0
sodium	1
bicarbonate	2
added	0
to	0
the	0
medication	0
11	0
(	0
58	0
%	0
)	0
complained	0
of	0
penile	3
pain	4
due	0
to	0
the	0
medication	0
","	0
while	0
only	0
1	0
of	0
the	0
19	0
men	0
(	0
5	0
%	0
)	0
who	0
received	0
sodium	1
bicarbonate	2
complained	0
of	0
penile	3
pain	4
.	0
From	0
these	0
data	0
we	0
conclude	0
that	0
the	0
penile	3
pain	4
following	0
intracorporeal	0
injections	0
is	0
most	0
likely	0
due	0
to	0
the	0
acidity	0
of	0
the	0
medication	0
","	0
which	0
can	0
be	0
overcome	0
by	0
elevating	0
the	0
pH	0
to	0
a	0
neutral	0
level	0
.	0
The	0
use	0
and	0
toxicity	3
of	0
didanosine	1
(	0
ddI	1
)	0
in	0
HIV	3
antibody	4
-	4
positive	4
individuals	0
intolerant	0
to	0
zidovudine	1
(	0
AZT	1
)	0
0ne	0
hundred	0
and	0
fifty	0
-	0
one	0
patients	0
intolerant	0
to	0
zidovudine	1
(	0
AZT	1
)	0
received	0
didanosine	1
(	0
ddI	1
)	0
to	0
a	0
maximum	0
dose	0
of	0
12	0
.	0
5	0
mg	0
/	0
kg	0
/	0
day	0
.	0
Patient	0
response	0
was	0
assessed	0
using	0
changes	0
in	0
CD4	0
+	0
lymphocyte	0
subset	0
count	0
","	0
HIV	0
p24	0
antigen	0
","	0
weight	0
","	0
and	0
quality	0
of	0
life	0
.	0
Seventy	0
patients	0
developed	0
major	0
opportunistic	3
infections	4
whilst	0
on	0
therapy	0
;	0
this	0
was	0
the	0
first	0
AIDS	3
diagnosis	0
in	0
17	0
.	0
0nly	0
minor	0
changes	0
in	0
CD4	0
+	0
lymphocyte	0
subset	0
count	0
were	0
observed	0
in	0
AIDS	3
patients	0
","	0
although	0
a	0
more	0
significant	0
rise	0
occurred	0
in	0
those	0
with	0
earlier	0
stages	0
of	0
disease	0
.	0
0f	0
those	0
positive	0
for	0
p24	0
antigen	0
at	0
the	0
commencement	0
of	0
the	0
study	0
67	0
%	0
showed	0
a	0
positive	0
response	0
","	0
and	0
this	0
was	0
most	0
likely	0
in	0
those	0
with	0
CD4	0
+	0
lymphocyte	0
subset	0
counts	0
above	0
100	0
mm3	0
.	0
A	0
positive	0
weight	0
response	0
was	0
seen	0
in	0
16	0
%	0
of	0
patients	0
.	0
Most	0
patients	0
showed	0
improvement	0
in	0
individual	0
parameters	0
and	0
global	0
score	0
of	0
quality	0
of	0
life	0
.	0
Adverse	0
reactions	0
possibly	0
attributable	0
to	0
didanosine	1
were	0
common	0
.	0
The	0
most	0
common	0
side	0
-	0
effect	0
was	0
diarrhoea	3
","	0
which	0
resulted	0
in	0
cessation	0
of	0
therapy	0
in	0
19	0
individuals	0
.	0
Peripheral	3
neuropathy	4
occurred	0
in	0
12	0
patients	0
and	0
pancreatitis	3
in	0
six	0
.	0
Thirteen	0
patients	0
developed	0
a	0
raised	0
serum	0
amylase	0
without	0
abdominal	3
pain	4
.	0
Seven	0
patients	0
developed	0
glucose	3
tolerance	4
curves	4
characteristic	0
of	0
diabetes	3
but	0
these	0
were	0
mild	0
","	0
did	0
not	0
require	0
treatment	0
and	0
returned	0
to	0
normal	0
on	0
ceasing	0
didanosine	1
.	0
Immunohistochemical	0
studies	0
with	0
antibodies	0
to	0
neurofilament	0
proteins	0
on	0
axonal	3
damage	4
in	0
experimental	0
focal	0
lesions	0
in	0
rat	0
.	0
Immunohistochemistry	0
with	0
monoclonal	0
antibodies	0
against	0
neurofilament	0
(	0
NF	0
)	0
proteins	0
of	0
middle	0
and	0
high	0
molecular	0
weight	0
class	0
","	0
NF	0
-	0
M	0
and	0
NF	0
-	0
H	0
","	0
was	0
used	0
to	0
study	0
axonal	3
injury	4
in	0
the	0
borderzone	0
of	0
focal	0
lesions	0
in	0
rats	0
.	0
Focal	0
injury	3
in	4
the	4
cortex	4
was	0
produced	0
by	0
infusion	0
of	0
lactate	1
at	0
acid	0
pH	0
or	0
by	0
stab	0
caused	0
by	0
needle	0
insertion	0
.	0
Infarcts	3
in	4
substantia	4
nigra	4
pars	4
reticulata	4
were	0
evoked	0
by	0
prolonged	0
pilocarpine	1
-	0
induced	0
status	3
epilepticus	4
.	0
Immunohistochemical	0
staining	0
for	0
NFs	0
showed	0
characteristic	0
terminal	0
clubs	0
of	0
axons	0
in	0
the	0
borderzone	0
of	0
lesions	0
.	0
Differences	0
in	0
the	0
labelling	0
pattern	0
occurred	0
with	0
different	0
antibodies	0
which	0
apparently	0
depended	0
on	0
molecular	0
weight	0
class	0
of	0
NFs	0
and	0
phosphorylation	0
state	0
.	0
These	0
immunohistochemical	0
changes	0
of	0
NFs	0
can	0
serve	0
as	0
a	0
marker	0
for	0
axonal	3
damage	4
in	0
various	0
experimental	0
traumatic	3
or	0
ischemic	0
lesions	0
.	0
Pharmacokinetic	0
and	0
clinical	0
studies	0
in	0
patients	0
with	0
cimetidine	1
-	0
associated	0
mental	0
confusion	3
.	0
15	0
cases	0
of	0
cimetidine	1
-	0
associated	0
mental	0
confusion	3
have	0
been	0
reported	0
.	0
In	0
order	0
that	0
this	0
syndrome	0
might	0
be	0
investigated	0
changes	0
in	0
mental	0
status	0
(	0
M	0
.	0
S	0
.	0
)	0
were	0
correlated	0
with	0
serum	0
concentrations	0
and	0
renal	0
and	0
hepatic	0
function	0
in	0
36	0
patients	0
","	0
30	0
patients	0
had	0
no	0
M	0
.	0
S	0
.	0
change	0
on	0
cimetidine	1
and	0
6	0
had	0
moderate	0
to	0
severe	0
changes	0
.	0
These	0
6	0
patients	0
had	0
both	0
renal	3
and	4
liver	4
dysfunction	4
(	0
P	0
less	0
than	0
0	0
.	0
5	0
)	0
","	0
as	0
well	0
as	0
cimetidine	1
trough	0
-	0
concentrations	0
of	0
more	0
than	0
1	0
.	0
25	0
microgram	0
/	0
ml	0
(	0
P	0
less	0
than	0
0	0
.	0
5	0
)	0
.	0
The	0
severity	0
of	0
M	0
.	0
S	0
.	0
changes	0
increased	0
as	0
trough	0
-	0
concentrations	0
rose	0
","	0
5	0
patients	0
had	0
lumbar	0
puncture	0
.	0
The	0
cerebrospinal	0
fluid	0
:	0
serum	0
ratio	0
of	0
cimetidine	1
concentrations	0
was	0
0	0
.	0
24	0
:	0
1	0
and	0
indicates	0
that	0
cimetidine	1
passes	0
the	0
blood	0
-	0
brain	0
barrier	0
;	0
it	0
also	0
raises	0
the	0
possibility	0
that	0
M	0
.	0
S	0
.	0
changes	0
are	0
due	0
to	0
blockade	0
of	0
histamine	1
H2	0
-	0
receptors	0
in	0
the	0
central	0
nervous	0
system	0
.	0
Patients	0
likely	0
to	0
have	0
both	0
raised	0
trough	0
-	0
concentrations	0
and	0
mental	0
confusion	3
are	0
those	0
with	0
both	0
severe	0
renal	3
and	4
hepatic	4
dysfunction	4
.	0
They	0
should	0
be	0
closely	0
observed	0
and	0
should	0
be	0
given	0
reduced	0
doses	0
of	0
cimetidine	1
.	0
Prospective	0
study	0
of	0
the	0
long	0
-	0
term	0
effects	0
of	0
somatostatin	0
analog	0
(	0
octreotide	1
)	0
on	0
gallbladder	0
function	0
and	0
gallstone	3
formation	0
in	0
Chinese	0
acromegalic	3
patients	0
.	0
This	0
article	0
reports	0
the	0
changes	0
in	0
gallbladder	0
function	0
examined	0
by	0
ultrasonography	0
in	0
20	0
Chinese	0
patients	0
with	0
active	0
acromegaly	3
treated	0
with	0
sc	0
injection	0
of	0
the	0
somatostatin	0
analog	0
octreotide	1
in	0
dosages	0
of	0
300	0
-	0
1500	0
micrograms	0
/	0
day	0
for	0
a	0
mean	0
of	0
24	0
.	0
2	0
+	0
/	0
-	0
13	0
.	0
9	0
months	0
.	0
During	0
treatment	0
with	0
octreotide	1
","	0
17	0
patients	0
developed	0
sludge	0
","	0
10	0
had	0
gallstones	3
","	0
and	0
1	0
developed	0
acute	3
cholecystitis	4
requiring	0
surgery	0
.	0
In	0
all	0
of	0
7	0
patients	0
examined	0
acutely	0
","	0
gallbladder	0
contractility	0
was	0
inhibited	0
after	0
a	0
single	0
100	0
-	0
micrograms	0
injection	0
.	0
In	0
8	0
patients	0
followed	0
for	0
24	0
weeks	0
","	0
gallbladder	0
contractility	0
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depressed	3
throughout	0
therapy	0
.	0
After	0
withdrawal	0
of	0
octreotide	1
in	0
10	0
patients	0
without	0
gallstones	3
","	0
8	0
patients	0
assessed	0
had	0
return	0
of	0
normal	0
gallbladder	0
contractility	0
within	0
1	0
month	0
.	0
In	0
8	0
of	0
the	0
remaining	0
10	0
patients	0
who	0
developed	0
gallstones	3
during	0
treatment	0
","	0
gallbladder	0
contractility	0
normalized	0
in	0
5	0
patients	0
(	0
3	0
of	0
whom	0
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disappearance	0
of	0
their	0
stones	0
within	0
3	0
weeks	0
)	0
","	0
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3	0
(	0
2	0
of	0
whom	0
had	0
stones	0
present	0
at	0
6	0
months	0
)	0
.	0
0ur	0
results	0
suggest	0
that	0
the	0
suppression	0
of	0
gallbladder	0
contractility	0
is	0
the	0
cause	0
of	0
the	0
successive	0
formation	0
of	0
bile	0
sludge	0
","	0
gallstones	3
","	0
and	0
cholecystitis	3
during	0
octreotide	1
therapy	0
in	0
Chinese	0
acromegalic	3
patients	0
.	0
It	0
is	0
therefore	0
very	0
important	0
to	0
follow	0
the	0
changes	0
of	0
gallbladder	0
function	0
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long	0
-	0
term	0
octreotide	1
therapy	0
of	0
acromegalic	3
patients	0
.	0
Increase	0
of	0
Parkinson	3
disability	4
after	0
fluoxetine	1
medication	0
.	0
Depression	3
is	0
a	0
major	0
clinical	0
feature	0
of	0
Parkinson	3
'	4
s	4
disease	4
.	0
We	0
report	0
the	0
increased	0
amount	0
of	0
motor	3
disability	4
in	0
four	0
patients	0
with	0
idiopathic	3
Parkinson	4
'	4
s	4
disease	4
after	0
exposure	0
to	0
the	0
antidepressant	1
fluoxetine	1
.	0
The	0
possibility	0
of	0
a	0
clinically	0
relevant	0
dopamine	1
-	0
antagonistic	0
capacity	0
of	0
fluoxetine	1
in	0
Parkinson	3
'	4
s	4
disease	4
patients	0
must	0
be	0
considered	0
.	0
Sinus	3
arrest	4
associated	0
with	0
continuous	0
-	0
infusion	0
cimetidine	1
.	0
The	0
administration	0
of	0
intermittent	0
intravenous	0
infusions	0
of	0
cimetidine	1
is	0
infrequently	0
associated	0
with	0
the	0
development	0
of	0
bradyarrhythmias	3
.	0
A	0
40	0
-	0
year	0
-	0
old	0
man	0
with	0
leukemia	3
and	0
no	0
history	0
of	0
cardiac	3
disease	4
developed	0
recurrent	0
","	0
brief	0
episodes	0
of	0
apparent	0
sinus	3
arrest	4
while	0
receiving	0
continuous	0
-	0
infusion	0
cimetidine	1
50	0
mg	0
/	0
hour	0
.	0
The	0
arrhythmias	3
were	0
temporally	0
related	0
to	0
cimetidine	1
administration	0
","	0
disappeared	0
after	0
dechallenge	0
","	0
and	0
did	0
not	0
recur	0
during	0
ranitidine	1
treatment	0
.	0
This	0
is	0
the	0
first	0
reported	0
case	0
of	0
sinus	3
arrest	4
associated	0
with	0
continuous	0
-	0
infusion	0
cimetidine	1
.	0
Phase	0
II	0
trial	0
of	0
vinorelbine	1
in	0
metastatic	0
squamous	3
cell	4
esophageal	4
carcinoma	4
.	0
European	0
0rganization	0
for	0
Research	0
and	0
Treatment	0
of	0
Cancer	3
Gastrointestinal	0
Treat	0
Cancer	3
Cooperative	0
Group	0
.	0
PURP0SE	0
:	0
To	0
evaluate	0
the	0
response	0
rate	0
and	0
toxic	0
effects	0
of	0
vinorelbine	1
(	0
VNB	1
)	0
administered	0
as	0
a	0
single	0
agent	0
in	0
metastatic	0
squamous	3
cell	4
esophageal	4
carcinoma	4
.	0
PATIENTS	0
AND	0
METH0DS	0
:	0
Forty	0
-	0
six	0
eligible	0
patients	0
with	0
measurable	0
lesions	0
were	0
included	0
and	0
were	0
stratified	0
according	0
to	0
previous	0
chemotherapy	0
.	0
Thirty	0
patients	0
without	0
prior	0
chemotherapy	0
and	0
16	0
pretreated	0
with	0
cisplatin	1
-	0
based	0
chemotherapy	0
were	0
assessable	0
for	0
toxicity	3
and	0
response	0
.	0
VNB	1
was	0
administered	0
weekly	0
as	0
a	0
25	0
-	0
mg	0
/	0
m2	0
short	0
intravenous	0
(	0
i	0
.	0
v	0
.	0
)	0
infusion	0
.	0
RESULTS	0
:	0
Six	0
of	0
30	0
patients	0
(	0
20	0
%	0
)	0
without	0
prior	0
chemotherapy	0
achieved	0
a	0
partial	0
response	0
(	0
PR	0
)	0
(	0
95	0
%	0
confidence	0
interval	0
[	0
CI	0
]	0
","	0
8	0
%	0
to	0
39	0
%	0
)	0
.	0
The	0
median	0
duration	0
of	0
response	0
was	0
21	0
weeks	0
(	0
range	0
","	0
17	0
to	0
28	0
)	0
.	0
0ne	0
of	0
16	0
patients	0
(	0
6	0
%	0
)	0
with	0
prior	0
chemotherapy	0
had	0
a	0
complete	0
response	0
(	0
CR	0
)	0
of	0
31	0
weeks	0
'	0
duration	0
(	0
95	0
%	0
CI	0
","	0
0	0
%	0
to	0
30	0
%	0
)	0
.	0
The	0
overall	0
response	0
rate	0
(	0
World	0
Health	0
0rganization	0
[	0
WH0	0
]	0
criteria	0
)	0
was	0
15	0
%	0
(	0
CR	0
","	0
2	0
%	0
;	0
PR	0
13	0
%	0
;	0
95	0
%	0
CI	0
","	0
6	0
%	0
to	0
29	0
%	0
)	0
.	0
The	0
median	0
dose	0
-	0
intensity	0
(	0
DI	0
)	0
was	0
20	0
mg	0
/	0
m2	0
/	0
wk	0
.	0
VNB	1
was	0
well	0
tolerated	0
and	0
zero	0
instances	0
of	0
WH0	0
grade	0
4	0
nonhematologic	0
toxicity	3
occurred	0
.	0
At	0
least	0
one	0
episode	0
of	0
grade	0
3	0
or	0
4	0
granulocytopenia	3
was	0
seen	0
in	0
59	0
%	0
of	0
patients	0
.	0
A	0
grade	0
2	0
or	0
3	0
infection	3
occurred	0
in	0
16	0
%	0
of	0
patients	0
","	0
but	0
no	0
toxic	0
deaths	3
occurred	0
.	0
0ther	0
side	0
effects	0
were	0
rare	0
","	0
and	0
peripheral	3
neurotoxicity	4
has	0
been	0
minor	0
(	0
26	0
%	0
grade	0
1	0
)	0
.	0
C0NCLUSI0N	0
:	0
These	0
data	0
indicate	0
that	0
VNB	1
is	0
an	0
active	0
agent	0
in	0
metastatic	0
esophageal	3
squamous	4
cell	4
carcinoma	4
.	0
Given	0
its	0
excellent	0
tolerance	0
profile	0
and	0
low	0
toxicity	3
","	0
further	0
evaluation	0
of	0
VNB	1
in	0
combination	0
therapy	0
is	0
warranted	0
.	0
Evaluation	0
of	0
adverse	0
reactions	0
of	0
aponidine	1
hydrochloride	2
ophthalmic	0
solution	0
.	0
We	0
prospectively	0
evaluated	0
the	0
adverse	0
reactions	0
of	0
apraclonidine	1
in	0
20	0
normal	0
volunteers	0
by	0
instilling	0
a	0
single	0
drop	0
of	0
1	0
%	0
apraclonidine	1
in	0
their	0
right	0
eyes	0
.	0
Examinations	0
","	0
including	0
blood	0
pressure	0
","	0
pulse	0
rate	0
","	0
conjunctiva	0
and	0
cornea	0
","	0
intraocular	0
pressure	0
(	0
I0P	0
)	0
","	0
pupil	0
diameter	0
","	0
basal	0
tear	0
secretion	0
and	0
margin	0
reflex	0
distance	0
of	0
both	0
upper	0
and	0
lower	0
eyelids	0
","	0
were	0
performed	0
prior	0
to	0
entry	0
and	0
at	0
1	0
","	0
3	0
","	0
5	0
and	0
7	0
hours	0
after	0
instillation	0
.	0
The	0
ocular	3
hypotensive	4
effects	0
were	0
statistically	0
significant	0
for	0
apraclonidine	1
-	0
treated	0
eyes	0
throughout	0
the	0
study	0
and	0
also	0
statistically	0
significant	0
for	0
contralateral	0
eyes	0
from	0
three	0
hours	0
after	0
topical	0
administration	0
of	0
1	0
%	0
apraclonidine	1
.	0
Decreases	3
in	4
systolic	4
blood	4
pressure	4
were	0
statistically	0
","	0
but	0
not	0
clinically	0
","	0
significant	0
.	0
No	0
significant	0
changes	0
in	0
diastolic	0
blood	0
pressure	0
","	0
pulse	0
rate	0
and	0
basal	0
tear	0
secretion	0
were	0
noted	0
.	0
Conjunctival	3
blanching	4
and	0
mydriasis	3
were	0
commonly	0
found	0
.	0
Upper	0
lid	0
retraction	0
was	0
frequently	0
noted	0
.	0
While	0
the	0
elevations	0
of	0
the	0
upper	0
lid	0
margin	0
in	0
most	0
subjects	0
were	0
not	0
more	0
than	0
2	0
mm	0
and	0
did	0
not	0
cause	0
noticeable	0
change	0
in	0
appearance	0
","	0
one	0
subject	0
suffered	0
from	0
mechanical	0
entropion	3
and	0
marked	0
corneal	3
abrasion	4
3	0
hours	0
after	0
instillation	0
of	0
the	0
medication	0
.	0
This	0
may	0
well	0
be	0
a	0
particularly	0
notable	0
finding	0
in	0
Asian	0
people	0
.	0
Thiopentone	1
pretreatment	0
for	0
propofol	1
injection	0
pain	3
in	0
ambulatory	0
patients	0
.	0
This	0
study	0
investigated	0
propofol	1
injection	0
pain	3
in	0
patients	0
undergoing	0
ambulatory	0
anaesthesia	0
.	0
In	0
a	0
randomized	0
","	0
double	0
-	0
blind	0
trial	0
","	0
90	0
women	0
were	0
allocated	0
to	0
receive	0
one	0
of	0
three	0
treatments	0
prior	0
to	0
induction	0
of	0
anaesthesia	0
with	0
propofol	1
.	0
Patients	0
in	0
Group	0
C	0
received	0
2	0
ml	0
normal	0
saline	0
","	0
Group	0
L	0
","	0
2	0
ml	0
","	0
lidocaine	1
2	0
%	0
(	0
40	0
mg	0
)	0
and	0
Group	0
T	0
","	0
2	0
ml	0
thiopentone	1
2	0
.	0
5	0
%	0
(	0
50	0
mg	0
)	0
.	0
Venous	0
discomfort	0
was	0
assessed	0
with	0
a	0
visual	0
analogue	0
scale	0
(	0
VAS	0
)	0
5	0
-	0
15	0
sec	0
after	0
commencing	0
propofol	1
administration	0
using	0
an	0
infusion	0
pump	0
(	0
rate	0
1000	0
micrograms	0
.	0
kg	0
-	0
1	0
.	0
min	0
-	0
1	0
)	0
.	0
Loss	3
of	4
consciousness	4
occurred	0
in	0
60	0
-	0
90	0
sec	0
.	0
Visual	0
analogue	0
scores	0
(	0
mean	0
+	0
/	0
-	0
SD	0
)	0
during	0
induction	0
were	0
lower	0
in	0
Groups	0
L	0
(	0
3	0
.	0
3	0
+	0
/	0
-	0
2	0
.	0
5	0
)	0
and	0
T	0
(	0
4	0
.	0
1	0
+	0
/	0
-	0
2	0
.	0
7	0
)	0
than	0
in	0
Group	0
C	0
(	0
5	0
.	0
6	0
+	0
/	0
-	0
2	0
.	0
3	0
)	0
;	0
P	0
=	0
0	0
.	0
31	0
.	0
The	0
incidence	0
of	0
venous	0
discomfort	0
was	0
lower	0
in	0
Group	0
L	0
(	0
76	0
.	0
6	0
%	0
;	0
P	0
<	0
0	0
.	0
5	0
)	0
than	0
in	0
Group	0
C	0
(	0
100	0
%	0
)	0
but	0
not	0
different	0
from	0
Group	0
T	0
(	0
90	0
%	0
)	0
.	0
The	0
VAS	0
scores	0
for	0
recall	0
of	0
pain	3
in	0
the	0
recovery	0
room	0
were	0
correlated	0
with	0
the	0
VAS	0
scores	0
during	0
induction	0
(	0
r	0
=	0
0	0
.	0
7045	0
;	0
P	0
<	0
0	0
.	0
1	0
)	0
.	0
Recovery	0
room	0
discharge	0
times	0
were	0
similar	0
:	0
C	0
(	0
75	0
.	0
9	0
+	0
/	0
-	0
19	0
.	0
4	0
min	0
)	0
;	0
L	0
73	0
.	0
6	0
+	0
/	0
-	0
21	0
.	0
6	0
min	0
)	0
;	0
T	0
(	0
77	0
.	0
1	0
+	0
/	0
-	0
18	0
.	0
9	0
min	0
)	0
.	0
Assessing	0
their	0
overall	0
satisfaction	0
","	0
89	0
.	0
7	0
%	0
would	0
choose	0
propofol	1
anaesthesia	0
again	0
.	0
We	0
conclude	0
that	0
lidocaine	1
reduces	0
the	0
incidence	0
and	0
severity	0
of	0
propofol	1
injection	0
pain	3
in	0
ambulatory	0
patients	0
whereas	0
thiopentone	1
only	0
reduces	0
its	0
severity	0
.	0
Persistent	0
paralysis	3
after	0
prolonged	0
use	0
of	0
atracurium	1
in	0
the	0
absence	0
of	0
corticosteroids	0
.	0
Neuromuscular	0
blocking	0
agents	0
(	0
NMBAs	0
)	0
are	0
often	0
used	0
for	0
patients	0
requiring	0
prolonged	0
mechanical	0
ventilation	0
.	0
Reports	0
of	0
persistent	0
paralysis	3
after	0
the	0
discontinuance	0
of	0
these	0
drugs	0
have	0
most	0
often	0
involved	0
aminosteroid	0
-	0
based	0
NMBAs	0
such	0
as	0
vecuronium	1
bromide	2
","	0
especially	0
when	0
used	0
in	0
conjunction	0
with	0
corticosteroids	0
.	0
Atracurium	1
besylate	2
","	0
a	0
short	0
-	0
acting	0
benzylisoquinolinium	1
NMBA	0
that	0
is	0
eliminated	0
independently	0
of	0
renal	0
or	0
hepatic	0
function	0
","	0
has	0
also	0
been	0
associated	0
with	0
persistent	0
paralysis	3
","	0
but	0
only	0
when	0
used	0
with	0
corticosteroids	0
.	0
We	0
report	0
a	0
case	0
of	0
atracurium	1
-	0
related	0
paralysis	3
persisting	0
for	0
approximately	0
50	0
hours	0
in	0
a	0
patient	0
who	0
was	0
not	0
treated	0
with	0
corticosteroids	0
.	0
A	0
phase	0
I	0
/	0
II	0
study	0
of	0
paclitaxel	1
plus	0
cisplatin	1
as	0
first	0
-	0
line	0
therapy	0
for	0
head	3
and	4
neck	4
cancers	4
:	0
preliminary	0
results	0
.	0
Improved	0
outcomes	0
among	0
patients	0
with	0
head	3
and	4
neck	4
carcinomas	4
require	0
investigations	0
of	0
new	0
drugs	0
for	0
induction	0
therapy	0
.	0
Preliminary	0
results	0
of	0
an	0
Eastern	0
Cooperative	0
0ncology	0
Group	0
study	0
of	0
single	0
-	0
agent	0
paclitaxel	1
(	0
Taxol	1
;	0
Bristol	0
-	0
Myers	0
Squibb	0
Company	0
","	0
Princeton	0
","	0
NJ	0
)	0
reported	0
a	0
37	0
%	0
response	0
rate	0
in	0
patients	0
with	0
head	3
and	4
neck	4
cancer	4
","	0
and	0
the	0
paclitaxel	1
/	0
cisplatin	1
combination	0
has	0
been	0
used	0
successfully	0
and	0
has	0
significantly	0
improved	0
median	0
response	0
duration	0
in	0
ovarian	3
cancer	4
patients	0
.	0
We	0
initiated	0
a	0
phase	0
I	0
/	0
II	0
trial	0
to	0
determine	0
the	0
response	0
and	0
toxicity	3
of	0
escalating	0
paclitaxel	1
doses	0
combined	0
with	0
fixed	0
-	0
dose	0
cisplatin	1
with	0
granulocyte	0
colony	0
-	0
stimulating	0
factor	0
support	0
in	0
patients	0
with	0
untreated	0
locally	0
advanced	0
inoperable	0
head	3
and	4
neck	4
carcinoma	4
.	0
To	0
date	0
","	0
23	0
men	0
with	0
a	0
median	0
age	0
of	0
50	0
years	0
and	0
good	0
performance	0
status	0
have	0
entered	0
the	0
trial	0
.	0
Primary	0
tumor	3
sites	0
were	0
oropharynx	0
","	0
10	0
patients	0
;	0
hypopharynx	0
","	0
four	0
;	0
larynx	0
","	0
two	0
;	0
oral	0
cavity	0
","	0
three	0
;	0
unknown	0
primary	0
","	0
two	0
;	0
and	0
nasal	0
cavity	0
and	0
parotid	0
gland	0
","	0
one	0
each	0
.	0
0f	0
20	0
patients	0
evaluable	0
for	0
toxicity	3
","	0
four	0
had	0
stage	0
III	0
and	0
16	0
had	0
stage	0
IV	0
disease	0
.	0
Treatment	0
","	0
given	0
every	0
21	0
days	0
for	0
a	0
maximum	0
of	0
three	0
cycles	0
","	0
consisted	0
of	0
paclitaxel	1
by	0
3	0
-	0
hour	0
infusion	0
followed	0
the	0
next	0
day	0
by	0
a	0
fixed	0
dose	0
of	0
cisplatin	1
(	0
75	0
mg	0
/	0
m2	0
)	0
.	0
The	0
dose	0
levels	0
incorporate	0
escalating	0
paclitaxel	1
doses	0
","	0
and	0
intrapatient	0
escalations	0
within	0
a	0
given	0
dose	0
level	0
are	0
permitted	0
if	0
toxicity	3
permits	0
.	0
At	0
the	0
time	0
of	0
this	0
writing	0
","	0
dose	0
level	0
4	0
(	0
260	0
","	0
270	0
","	0
and	0
280	0
mg	0
/	0
m2	0
)	0
is	0
being	0
evaluated	0
;	0
three	0
patients	0
from	0
this	0
level	0
are	0
evaluable	0
.	0
With	0
paclitaxel	1
doses	0
of	0
200	0
mg	0
/	0
m2	0
and	0
higher	0
","	0
granulocyte	0
colony	0
-	0
stimulating	0
factor	0
5	0
micrograms	0
/	0
kg	0
/	0
d	0
is	0
given	0
(	0
days	0
4	0
through	0
12	0
)	0
.	0
0f	0
18	0
patients	0
evaluable	0
for	0
response	0
","	0
seven	0
(	0
39	0
%	0
)	0
achieved	0
a	0
complete	0
response	0
and	0
six	0
(	0
33	0
%	0
)	0
achieved	0
a	0
partial	0
response	0
.	0
Three	0
patients	0
had	0
no	0
change	0
and	0
disease	0
progressed	0
in	0
two	0
.	0
The	0
overall	0
response	0
rate	0
is	0
72	0
%	0
.	0
Eleven	0
responding	0
patients	0
had	0
subsequent	0
surgery	0
/	0
radiotherapy	0
or	0
radical	0
radiotherapy	0
.	0
Two	0
pathologic	0
complete	0
responses	0
were	0
observed	0
in	0
patients	0
who	0
had	0
achieved	0
clinical	0
complete	0
responses	0
.	0
Alopecia	3
","	0
paresthesias	3
","	0
and	0
arthralgias	3
/	0
myalgias	3
have	0
occurred	0
frequently	0
","	0
but	0
with	0
one	0
exception	0
(	0
a	0
grade	0
3	0
myalgia	3
)	0
they	0
have	0
been	0
grade	0
1	0
or	0
2	0
.	0
No	0
dose	0
-	0
limiting	0
hematologic	0
toxicity	3
has	0
been	0
seen	0
.	0
Paclitaxel	1
/	0
cisplatin	1
is	0
an	0
effective	0
first	0
-	0
line	0
regimen	0
for	0
locoregionally	0
advanced	0
head	3
and	4
neck	4
cancer	4
and	0
continued	0
study	0
is	0
warranted	0
.	0
Results	0
thus	0
far	0
suggest	0
no	0
dose	0
-	0
response	0
effect	0
for	0
paclitaxel	1
doses	0
above	0
200	0
mg	0
/	0
m2	0
.	0
Improvement	0
of	0
levodopa	1
-	0
induced	0
dyskinesia	3
by	0
propranolol	1
in	0
Parkinson	3
'	4
s	4
disease	4
.	0
Seven	0
patients	0
suffering	0
from	0
Parkinson	3
'	4
s	4
disease	4
(	0
PD	3
)	0
with	0
severely	0
disabling	0
dyskinesia	3
received	0
low	0
-	0
dose	0
propranolol	1
as	0
an	0
adjunct	0
to	0
the	0
currently	0
used	0
medical	0
treatment	0
.	0
There	0
was	0
a	0
significant	0
40	0
%	0
improvement	0
in	0
the	0
dyskinesia	3
score	0
without	0
increase	0
of	0
parkinsonian	3
motor	3
disability	4
.	0
Ballistic	0
and	0
choreic	0
dyskinesia	3
were	0
markedly	0
ameliorated	0
","	0
whereas	0
dystonia	3
was	0
not	0
.	0
This	0
study	0
suggests	0
that	0
administration	0
of	0
low	0
doses	0
of	0
beta	0
-	0
blockers	0
may	0
improve	0
levodopa	1
-	0
induced	0
ballistic	0
and	0
choreic	0
dyskinesia	3
in	0
PD	3
.	0
Habitual	0
use	0
of	0
acetaminophen	1
as	0
a	0
risk	0
factor	0
for	0
chronic	3
renal	4
failure	4
:	0
a	0
comparison	0
with	0
phenacetin	1
.	0
Six	0
epidemiologic	0
studies	0
in	0
the	0
United	0
States	0
and	0
Europe	0
indicate	0
that	0
habitual	0
use	0
of	0
phenacetin	1
is	0
associated	0
with	0
the	0
development	0
of	0
chronic	3
renal	4
failure	4
and	0
end	3
-	4
stage	4
renal	4
disease	4
(	0
ESRD	3
)	0
","	0
with	0
a	0
relative	0
risk	0
in	0
the	0
range	0
of	0
4	0
to	0
19	0
.	0
As	0
a	0
result	0
of	0
these	0
and	0
other	0
studies	0
","	0
phenacetin	1
has	0
now	0
been	0
withdrawn	0
from	0
the	0
market	0
in	0
most	0
countries	0
.	0
However	0
","	0
three	0
case	0
control	0
studies	0
","	0
one	0
each	0
in	0
North	0
Carolina	0
","	0
northern	0
Maryland	0
","	0
and	0
West	0
Berlin	0
","	0
Germany	0
","	0
showed	0
that	0
habitual	0
use	0
of	0
acetaminophen	1
is	0
also	0
associated	0
with	0
chronic	3
renal	4
failure	4
and	0
ESRD	3
","	0
with	0
a	0
relative	0
risk	0
in	0
the	0
range	0
of	0
2	0
to	0
4	0
.	0
These	0
studies	0
suggest	0
that	0
both	0
phenacetin	1
and	0
acetaminophen	1
may	0
contribute	0
to	0
the	0
burden	0
of	0
ESRD	3
","	0
with	0
the	0
risk	0
of	0
the	0
latter	0
being	0
somewhat	0
less	0
than	0
that	0
of	0
the	0
former	0
.	0
This	0
apparent	0
difference	0
in	0
risk	0
may	0
not	0
be	0
due	0
to	0
differences	0
in	0
nephrotoxic	3
potential	0
of	0
the	0
drugs	0
themselves	0
.	0
A	0
lower	0
relative	0
risk	0
would	0
be	0
expected	0
for	0
acetaminophen	1
if	0
the	0
risk	0
of	0
both	0
drugs	0
in	0
combination	0
with	0
other	0
analgesics	0
was	0
higher	0
than	0
the	0
risk	0
of	0
either	0
agent	0
alone	0
.	0
Thus	0
","	0
acetaminophen	1
has	0
been	0
used	0
both	0
as	0
a	0
single	0
agent	0
and	0
in	0
combination	0
with	0
other	0
analgesics	0
","	0
whereas	0
phenacetin	1
was	0
available	0
only	0
in	0
combinations	0
.	0
The	0
possibility	0
that	0
habitual	0
use	0
of	0
acetaminophen	1
alone	0
increases	0
the	0
risk	0
of	0
ESRD	3
has	0
not	0
been	0
clearly	0
demonstrated	0
","	0
but	0
cannot	0
be	0
dismissed	0
.	0
Acetaminophen	1
-	0
induced	0
hypotension	3
.	0
Through	0
30	0
years	0
of	0
widespread	0
use	0
","	0
acetaminophen	1
has	0
been	0
shown	0
to	0
be	0
a	0
remarkably	0
safe	0
medication	0
in	0
therapeutic	0
dosages	0
.	0
The	0
potential	0
for	0
acetaminophen	1
to	0
produce	0
cardiovascular	3
toxicities	4
is	0
very	0
low	0
.	0
However	0
","	0
acetaminophen	1
has	0
been	0
demonstrated	0
to	0
produce	0
symptoms	0
of	0
anaphylaxis	3
","	0
including	0
hypotension	3
","	0
in	0
sensitive	0
individuals	0
.	0
This	0
article	0
describes	0
two	0
critically	3
ill	4
patients	0
in	0
whom	0
transient	0
episodes	0
of	0
hypotension	3
reproducibly	0
developed	0
after	0
administration	0
of	0
acetaminophen	1
.	0
0ther	0
symptoms	0
of	0
allergic	3
reactions	4
were	0
not	0
clinically	0
detectable	0
.	0
The	0
hypotensive	3
episodes	0
were	0
severe	0
enough	0
to	0
require	0
vasopressor	0
administration	0
.	0
The	0
reports	0
illustrate	0
the	0
need	0
for	0
clinicians	0
to	0
consider	0
acetaminophen	1
in	0
patients	0
with	0
hypotension	3
of	0
unknown	0
origin	0
.	0
Reduction	0
of	0
heparan	1
sulphate	2
-	0
associated	0
anionic	0
sites	0
in	0
the	0
glomerular	0
basement	0
membrane	0
of	0
rats	0
with	0
streptozotocin	1
-	0
induced	0
diabetic	3
nephropathy	4
.	0
Heparan	1
sulphate	2
-	0
associated	0
anionic	0
sites	0
in	0
the	0
glomerular	0
basement	0
membrane	0
were	0
studied	0
in	0
rats	0
8	0
months	0
after	0
induction	0
of	0
diabetes	3
by	0
streptozotocin	1
and	0
in	0
age	0
-	0
adn	0
sex	0
-	0
matched	0
control	0
rats	0
","	0
employing	0
the	0
cationic	0
dye	0
cuprolinic	1
blue	2
.	0
Morphometric	0
analysis	0
at	0
the	0
ultrastructural	0
level	0
was	0
performed	0
using	0
a	0
computerized	0
image	0
processor	0
.	0
The	0
heparan	1
sulphate	2
specificity	0
of	0
the	0
cuprolinic	1
blue	2
staining	0
was	0
demonstrated	0
by	0
glycosaminoglycan	1
-	0
degrading	0
enzymes	0
","	0
showing	0
that	0
pretreatment	0
of	0
the	0
sections	0
with	0
heparitinase	0
abolished	0
all	0
staining	0
","	0
whereas	0
chondroitinase	0
ABC	0
had	0
no	0
effect	0
.	0
The	0
majority	0
of	0
anionic	0
sites	0
(	0
74	0
%	0
in	0
diabetic	3
and	0
81	0
%	0
in	0
control	0
rats	0
)	0
were	0
found	0
within	0
the	0
lamina	0
rara	0
externa	0
of	0
the	0
glomerular	0
basement	0
membrane	0
.	0
A	0
minority	0
of	0
anionic	0
sites	0
were	0
scattered	0
throughout	0
the	0
lamina	0
densa	0
and	0
lamina	0
rara	0
interna	0
","	0
and	0
were	0
significantly	0
smaller	0
than	0
those	0
in	0
the	0
lamina	0
rara	0
externa	0
of	0
the	0
glomerular	0
basement	0
membrane	0
(	0
p	0
<	0
0	0
.	0
1	0
and	0
p	0
<	0
0	0
.	0
1	0
for	0
diabetic	3
and	0
control	0
rats	0
","	0
respectively	0
)	0
.	0
Diabetic	3
rats	0
progressively	0
developed	0
albuminuria	3
reaching	0
40	0
.	0
3	0
(	0
32	0
.	0
2	0
-	0
62	0
.	0
0	0
)	0
mg	0
/	0
24	0
h	0
after	0
8	0
months	0
in	0
contrast	0
to	0
the	0
control	0
animals	0
(	0
0	0
.	0
8	0
(	0
0	0
.	0
2	0
-	0
0	0
.	0
9	0
)	0
mg	0
/	0
24	0
h	0
","	0
p	0
<	0
0	0
.	0
2	0
)	0
.	0
At	0
the	0
same	0
time	0
","	0
the	0
number	0
of	0
heparan	1
sulphate	2
anionic	0
sites	0
and	0
the	0
total	0
anionic	0
site	0
surface	0
(	0
number	0
of	0
anionic	0
sites	0
x	0
mean	0
anionic	0
site	0
surface	0
)	0
in	0
the	0
lamina	0
rara	0
externa	0
of	0
the	0
glomerular	0
basement	0
membrane	0
was	0
reduced	0
by	0
19	0
%	0
(	0
p	0
<	0
0	0
.	0
21	0
)	0
and	0
by	0
26	0
%	0
(	0
p	0
<	0
0	0
.	0
2	0
)	0
","	0
respectively	0
.	0
Number	0
and	0
total	0
anionic	0
site	0
surface	0
in	0
the	0
remaining	0
part	0
of	0
the	0
glomerular	0
basement	0
membrane	0
(	0
lamina	0
densa	0
and	0
lamina	0
rara	0
interna	0
)	0
were	0
not	0
significantly	0
changed	0
.	0
We	0
conclude	0
that	0
in	0
streptozotocin	1
-	0
diabetic	3
rats	0
with	0
an	0
increased	0
urinary	0
albumin	0
excretion	0
","	0
a	0
reduced	0
heparan	1
sulphate	2
charge	0
barrier	0
/	0
density	0
is	0
found	0
at	0
the	0
lamina	0
rara	0
externa	0
of	0
the	0
glomerular	0
basement	0
membrane	0
.	0
Mediation	0
of	0
enhanced	0
reflex	0
vagal	0
bradycardia	3
by	0
L	1
-	2
dopa	2
via	0
central	0
dopamine	1
formation	0
in	0
dogs	0
.	0
L	1
-	2
Dopa	2
(	0
5	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
decreased	0
blood	0
pressure	0
and	0
heart	0
rate	0
after	0
extracerebral	0
decarboxylase	0
inhibition	0
with	0
MK	1
-	2
486	2
(	0
25	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
in	0
anesthetize	0
MA0	1
-	0
inhibited	0
dogs	0
.	0
In	0
addition	0
","	0
reflex	0
bradycardia	3
caused	0
by	0
injected	0
norepinephrine	1
was	0
significantly	0
enhanced	0
by	0
L	1
-	2
dopa	2
","	0
DL	1
-	2
Threo	2
-	2
dihydroxyphenylserine	2
had	0
no	0
effect	0
on	0
blood	0
pressure	0
","	0
heart	0
rate	0
or	0
reflex	0
responses	0
to	0
norepinephrine	1
.	0
FLA	1
-	2
63	2
","	0
a	0
dopamine	1
-	0
beta	0
-	0
oxidase	0
inhibitor	0
","	0
did	0
not	0
have	0
any	0
effect	0
on	0
the	0
hypotension	3
","	0
bradycardia	3
or	0
reflex	0
-	0
enhancing	0
effect	0
of	0
L	1
-	2
dopa	2
.	0
Pimozide	1
did	0
not	0
affect	0
the	0
actions	0
of	0
L	1
-	2
dopa	2
on	0
blood	0
pressure	0
and	0
heart	0
rate	0
but	0
completely	0
blocked	0
the	0
enhancement	0
of	0
reflexes	0
.	0
Removal	0
of	0
the	0
carotid	0
sinuses	0
caused	0
an	0
elevation	0
blood	0
pressure	0
and	0
heart	0
rate	0
and	0
abolished	0
the	0
negative	0
chronotropic	0
effect	0
of	0
norepinephrine	1
.	0
However	0
","	0
L	1
-	2
dopa	2
restored	0
the	0
bradycardia	3
caused	0
by	0
norepinephrine	1
in	0
addition	0
to	0
decreasing	0
blood	0
pressure	0
and	0
heart	0
rate	0
.	0
5	1
-	2
HTP	2
(	0
5	0
mg	0
/	0
kg	0
i	0
.	0
v	0
.	0
)	0
decreased	0
blood	0
pressure	0
and	0
heart	0
rate	0
and	0
decreased	0
the	0
reflex	0
bradycardia	3
to	0
norepinephrine	1
.	0
It	0
is	0
concluded	0
that	0
L	1
-	2
dopa	2
enhances	0
reflex	0
bradycardia	3
through	0
central	0
alpha	0
-	0
receptor	0
stimulation	0
.	0
Furthermore	0
","	0
the	0
effects	0
are	0
mediated	0
through	0
dopamine	1
rather	0
than	0
norepinephrine	1
and	0
do	0
not	0
require	0
the	0
carotid	0
sinus	0
baroreceptors	0
.	0
Microangiopathic	3
hemolytic	4
anemia	4
complicating	0
FK506	1
(	0
tacrolimus	1
)	0
therapy	0
.	0
We	0
describe	0
3	0
episodes	0
of	0
microangiopathic	3
hemolytic	4
anemia	4
(	0
MAHA	3
)	0
in	0
2	0
solid	0
organ	0
recipients	0
under	0
FK506	1
(	0
tacrolimus	1
)	0
therapy	0
.	0
In	0
both	0
cases	0
","	0
discontinuation	0
of	0
FK506	1
and	0
treatment	0
with	0
plasma	0
exchange	0
","	0
fresh	0
frozen	0
plasma	0
replacement	0
","	0
corticosteroids	1
","	0
aspirin	1
","	0
and	0
dipyridamole	1
led	0
to	0
resolution	0
of	0
MAHA	3
.	0
In	0
one	0
patient	0
","	0
reintroduction	0
of	0
FK506	1
led	0
to	0
rapid	0
recurrence	0
of	0
MAHA	3
.	0
FK506	1
-	0
associated	0
MAHA	3
is	0
probably	0
rare	0
but	0
physicians	0
must	0
be	0
aware	0
of	0
this	0
severe	0
complication	0
.	0
In	0
our	0
experience	0
and	0
according	0
to	0
the	0
literature	0
","	0
FK506	1
does	0
not	0
seem	0
to	0
cross	0
-	0
react	0
with	0
cyclosporin	1
A	2
(	0
CyA	1
)	0
","	0
an	0
immuno	0
-	0
suppressive	0
drug	0
already	0
known	0
to	0
induce	0
MAHA	3
.	0
Effect	0
of	0
some	0
anticancer	0
drugs	0
and	0
combined	0
chemotherapy	0
on	0
renal	3
toxicity	4
.	0
The	0
nephrotoxic	3
action	0
of	0
anticancer	0
drugs	0
such	0
as	0
nitrogranulogen	1
(	0
NG	1
)	0
","	0
methotrexate	1
(	0
MTX	1
)	0
","	0
5	1
-	2
fluorouracil	2
(	0
5	1
-	2
FU	2
)	0
and	0
cyclophosphamide	1
(	0
CY	1
)	0
administered	0
alone	0
or	0
in	0
combination	0
[	0
MTX	1
+	0
5	1
-	2
FU	2
+	0
CY	1
(	0
CMF	0
)	0
]	0
was	0
evaluated	0
in	0
experiments	0
on	0
Wistar	0
rats	0
.	0
After	0
drug	0
administration	0
","	0
creatinine	1
concentrations	0
in	0
the	0
plasma	0
and	0
in	0
the	0
urine	0
of	0
the	0
rats	0
were	0
determined	0
","	0
as	0
well	0
as	0
creatinine	1
clearance	0
.	0
Histopathologic	0
evaluation	0
of	0
the	0
kidneys	0
was	0
also	0
performed	0
.	0
After	0
MTX	1
administration	0
a	0
significant	0
increase	0
(	0
p	0
=	0
0	0
.	0
228	0
)	0
in	0
the	0
plasma	0
creatinine	1
concentration	0
and	0
a	0
significant	0
(	0
p	0
=	0
0	0
.	0
1	0
)	0
decrease	0
in	0
creatinine	1
clearance	0
was	0
noted	0
compared	0
to	0
controls	0
.	0
After	0
the	0
administration	0
of	0
NG	1
","	0
5	1
-	2
FU	2
and	0
CY	1
neither	0
a	0
statistically	0
significant	0
increase	0
in	0
creatinine	1
concentration	0
nor	0
an	0
increase	0
in	0
creatinine	1
clearance	0
was	0
observed	0
compared	0
to	0
the	0
group	0
receiving	0
no	0
cytostatics	0
.	0
Following	0
polytherapy	0
according	0
to	0
the	0
CMF	0
regimen	0
","	0
a	0
statistically	0
significant	0
decrease	0
(	0
p	0
=	0
0	0
.	0
343	0
)	0
in	0
creatinine	1
clearance	0
was	0
found	0
","	0
but	0
creatinine	1
concentration	0
did	0
not	0
increase	0
significantly	0
compared	0
to	0
controls	0
.	0
CY	1
caused	0
hemorrhagic	3
cystitis	4
in	0
40	0
%	0
of	0
rats	0
","	0
but	0
it	0
did	0
not	0
cause	0
this	0
complication	0
when	0
combined	0
with	0
5	1
-	2
FU	2
and	0
MTX	1
.	0
Histologic	0
changes	0
were	0
found	0
in	0
rat	0
kidneys	0
after	0
administration	0
of	0
MTX	1
","	0
CY	1
and	0
NG	1
","	0
while	0
no	0
such	0
change	0
was	0
observed	0
after	0
5	1
-	2
FU	2
and	0
joint	0
administration	0
of	0
MTX	1
+	0
5	1
-	2
FU	2
+	0
CY	1
compared	0
to	0
controls	0
.	0
0ur	0
studies	0
indicate	0
that	0
nephrotoxicity	3
of	0
MTX	1
+	0
5	1
-	2
FU	2
+	0
CY	1
administered	0
jointly	0
is	0
lower	0
than	0
in	0
monotherapy	0
.	0
The	0
interpeduncular	0
nucleus	0
regulates	0
nicotine	1
'	0
s	0
effects	0
on	0
free	0
-	0
field	0
activity	0
.	0
Partial	0
lesions	0
were	0
made	0
with	0
kainic	1
acid	2
in	0
the	0
interpeduncular	0
nucleus	0
of	0
the	0
ventral	0
midbrain	0
of	0
the	0
rat	0
.	0
Compared	0
with	0
sham	0
-	0
operated	0
controls	0
","	0
lesions	0
significantly	0
(	0
p	0
<	0
0	0
.	0
25	0
)	0
blunted	0
the	0
early	0
(	0
<	0
60	0
min	0
)	0
free	0
-	0
field	0
locomotor	3
hypoactivity	4
caused	0
by	0
nicotine	1
(	0
0	0
.	0
5	0
mg	0
kg	0
(	0
-	0
1	0
)	0
","	0
i	0
.	0
m	0
.	0
)	0
","	0
enhanced	0
the	0
later	0
(	0
60	0
-	0
120	0
min	0
)	0
nicotine	1
-	0
induced	0
hyperactivity	3
","	0
and	0
raised	0
spontaneous	0
nocturnal	0
activity	0
.	0
Lesions	0
reduced	0
the	0
extent	0
of	0
immunohistological	0
staining	0
for	0
choline	1
acetyltransferase	0
in	0
the	0
interpeduncular	0
nucleus	0
(	0
p	0
<	0
0	0
.	0
25	0
)	0
","	0
but	0
not	0
for	0
tyrosine	1
hydroxylase	0
in	0
the	0
surrounding	0
catecholaminergic	0
A10	0
region	0
.	0
We	0
conclude	0
that	0
the	0
interpeduncular	0
nucleus	0
mediates	0
nicotinic	0
depression	3
of	0
locomotor	0
activity	0
and	0
dampens	0
nicotinic	0
arousal	0
mechanisms	0
located	0
elsewhere	0
in	0
the	0
brain	0
.	0
Lithium	1
-	0
associated	0
cognitive	3
and	4
functional	4
deficits	4
reduced	0
by	0
a	0
switch	0
to	0
divalproex	1
sodium	2
:	0
a	0
case	0
series	0
.	0
BACKGR0UND	0
:	0
Lithium	1
remains	0
a	0
first	0
-	0
line	0
treatment	0
for	0
the	0
acute	0
and	0
maintenance	0
treatment	0
of	0
bipolar	3
disorder	4
.	0
Although	0
much	0
has	0
been	0
written	0
about	0
the	0
management	0
of	0
the	0
more	0
common	0
adverse	0
effects	0
of	0
lithium	1
","	0
such	0
as	0
polyuria	3
and	0
tremor	3
","	0
more	0
subtle	0
lithium	1
side	0
effects	0
such	0
as	0
cognitive	3
deficits	4
","	0
loss	3
of	4
creativity	4
","	0
and	0
functional	3
impairments	4
remain	0
understudied	0
.	0
This	0
report	0
summarizes	0
our	0
experience	0
in	0
switching	0
bipolar	3
patients	0
from	0
lithium	1
to	0
divalproex	1
sodium	2
to	0
alleviate	0
such	0
cognitive	3
and	4
functional	4
impairments	4
.	0
METH0D	0
:	0
0pen	0
","	0
case	0
series	0
design	0
.	0
RESULTS	0
:	0
We	0
report	0
seven	0
cases	0
where	0
substitution	0
of	0
lithium	1
","	0
either	0
fully	0
or	0
partially	0
","	0
with	0
divalproex	1
sodium	2
was	0
extremely	0
helpful	0
in	0
reducing	0
the	0
cognitive	3
","	4
motivational	4
","	4
or	4
creative	4
deficits	4
attributed	0
to	0
lithium	1
in	0
our	0
bipolar	3
patients	0
.	0
C0NCLUSI0N	0
:	0
In	0
this	0
preliminary	0
report	0
","	0
divalproex	1
sodium	2
was	0
a	0
superior	0
alternative	0
to	0
lithium	1
in	0
bipolar	3
patients	0
experiencing	0
cognitive	3
deficits	4
","	0
loss	3
of	4
creativity	4
","	0
and	0
functional	3
impairments	4
.	0
Effect	0
of	0
nifedipine	1
on	0
renal	0
function	0
in	0
liver	0
transplant	0
recipients	0
receiving	0
tacrolimus	1
.	0
The	0
effect	0
of	0
nifedipine	1
on	0
renal	0
function	0
in	0
liver	0
transplant	0
recipients	0
who	0
were	0
receiving	0
tacrolimus	1
was	0
evaluated	0
between	0
January	0
1992	0
and	0
January	0
1996	0
.	0
Two	0
groups	0
of	0
patients	0
receiving	0
tacrolimus	1
were	0
compared	0
over	0
a	0
period	0
of	0
1	0
year	0
","	0
one	0
group	0
comprising	0
hypertensive	3
patients	0
who	0
were	0
receiving	0
nifedipine	1
","	0
and	0
the	0
other	0
comprising	0
nonhypertensive	0
patients	0
not	0
receiving	0
nifedipine	1
.	0
The	0
time	0
from	0
transplant	0
to	0
baseline	0
was	0
similar	0
in	0
all	0
patients	0
.	0
Nifedipine	1
significantly	0
improved	0
kidney	0
function	0
as	0
indicated	0
by	0
a	0
significant	0
lowering	0
of	0
serum	0
creatinine	1
levels	0
at	0
6	0
and	0
12	0
months	0
.	0
The	0
observed	0
positive	0
impact	0
of	0
nifedipine	1
on	0
reducing	0
the	0
nephrotoxicity	3
associated	0
with	0
tacrolimus	1
in	0
liver	0
transplant	0
recipients	0
should	0
be	0
an	0
important	0
factor	0
in	0
selecting	0
an	0
agent	0
to	0
treat	0
hypertension	3
in	0
this	0
population	0
.	0
Alpha	0
and	0
beta	0
coma	3
in	0
drug	0
intoxication	0
uncomplicated	0
by	0
cerebral	3
hypoxia	4
.	0
Four	0
patients	0
who	0
were	0
rendered	0
comatose	3
or	0
stuporous	3
by	0
drug	0
intoxication	0
","	0
but	0
who	0
were	0
not	0
hypoxic	0
","	0
are	0
described	0
.	0
Three	0
patients	0
received	0
high	0
doses	0
of	0
chlormethiazole	1
for	0
alcohol	1
withdrawal	3
symptoms	4
","	0
and	0
one	0
took	0
a	0
suicidal	0
overdose	3
of	0
nitrazepam	1
.	0
The	0
patient	0
with	0
nitrazepam	1
overdose	3
and	0
two	0
of	0
those	0
with	0
chlormethiazole	1
intoxication	0
conformed	0
to	0
the	0
criteria	0
of	0
'	0
alpha	0
coma	3
'	0
","	0
showing	0
non	0
-	0
reactive	0
generalized	0
or	0
frontally	0
predominant	0
alpha	0
activity	0
in	0
the	0
EEG	0
.	0
The	0
fourth	0
patient	0
who	0
was	0
unconscious	0
after	0
chlormethiazole	1
administration	0
exhibite	0
generalized	0
non	0
-	0
reactive	0
activity	0
in	0
the	0
slow	0
beta	0
range	0
.	0
All	0
four	0
recovered	0
completely	0
without	0
neurological	3
sequelae	4
following	0
the	0
withdrawal	0
of	0
the	0
offending	0
agents	0
.	0
The	0
similarities	0
between	0
the	0
effects	0
of	0
structural	0
lesions	0
and	0
pharmacological	0
depression	3
of	0
the	0
brain	0
stem	0
reticular	0
formation	0
are	0
discussed	0
.	0
It	0
is	0
suggested	0
that	0
in	0
both	0
situations	0
disturbed	0
reticulo	0
-	0
thalamic	0
interactions	0
are	0
important	0
in	0
the	0
pathogenesis	0
of	0
alpha	0
coma	3
.	0
It	0
is	0
concluded	0
that	0
when	0
this	0
electroencephalographic	0
and	0
behavioural	0
picture	0
is	0
seen	0
in	0
drug	0
intoxication	0
","	0
in	0
the	0
absence	0
of	0
significant	0
hypoxaemia	3
","	0
a	0
favourable	0
outcome	0
may	0
be	0
anticipated	0
.	0
Magnetic	0
resonance	0
volumetry	0
of	0
the	0
cerebellum	0
in	0
epileptic	3
patients	0
after	0
phenytoin	1
overdosages	3
.	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
evaluate	0
the	0
relationship	0
between	0
phenytoin	1
medication	0
and	0
cerebellar	3
atrophy	4
in	0
patients	0
who	0
had	0
experienced	0
clinical	0
intoxication	0
.	0
Five	0
females	0
and	0
6	0
males	0
","	0
21	0
-	0
59	0
years	0
of	0
age	0
","	0
were	0
examined	0
with	0
a	0
1	0
.	0
5	0
-	0
T	0
whole	0
-	0
body	0
system	0
using	0
a	0
circular	0
polarized	0
head	0
coil	0
.	0
Conventional	0
spin	0
echo	0
images	0
were	0
acquired	0
in	0
the	0
sagittal	0
and	0
transverse	0
orientation	0
.	0
In	0
addition	0
","	0
we	0
performed	0
a	0
high	0
-	0
resolution	0
3D	0
gradient	0
echo	0
","	0
T1	0
-	0
weighted	0
sequences	0
at	0
a	0
1	0
-	0
mm	0
slice	0
thickness	0
.	0
The	0
images	0
were	0
subsequently	0
processed	0
to	0
obtain	0
volumetric	0
data	0
for	0
the	0
cerebellum	0
.	0
Cerebellar	0
volume	0
for	0
the	0
patient	0
group	0
ranged	0
between	0
67	0
.	0
66	0
and	0
131	0
.	0
8	0
ml	0
(	0
mean	0
108	0
.	0
9	0
ml	0
)	0
.	0
In	0
addition	0
3D	0
gradient	0
echo	0
data	0
sets	0
from	0
10	0
healthy	0
male	0
and	0
10	0
healthy	0
female	0
age	0
-	0
matched	0
volunteers	0
were	0
used	0
to	0
compare	0
cerebellar	0
volumes	0
.	0
Using	0
linear	0
regression	0
we	0
found	0
that	0
no	0
correlation	0
exists	0
between	0
seizure	3
duration	0
","	0
elevation	0
of	0
phenytoin	1
serum	0
levels	0
and	0
cerebellar	0
volume	0
.	0
However	0
","	0
multiple	0
regression	0
for	0
the	0
daily	0
dosage	0
","	0
duration	0
of	0
phenytoin	1
treatment	0
and	0
cerebellar	0
volume	0
revealed	0
a	0
correlation	0
of	0
these	0
parameters	0
.	0
We	0
conclude	0
that	0
phenytoin	1
overdosage	3
does	0
not	0
necessarily	0
result	0
in	0
cerebellar	3
atrophy	4
and	0
it	0
is	0
unlikely	0
that	0
phenytoin	1
medication	0
was	0
the	0
only	0
cause	0
of	0
cerebellar	3
atrophy	4
in	0
the	0
remaining	0
patients	0
.	0
Quantitative	0
morphometric	0
studies	0
of	0
the	0
cerebellum	0
provide	0
valuable	0
insights	0
into	0
the	0
pathogenesis	0
of	0
cerebellar	3
disorders	4
.	0
Late	0
recovery	0
of	0
renal	0
function	0
in	0
a	0
woman	0
with	0
the	0
hemolytic	3
uremic	4
syndrome	4
.	0
A	0
case	0
is	0
reported	0
of	0
the	0
hemolytic	3
uremic	4
syndrome	4
(	0
HUS	3
)	0
in	0
a	0
woman	0
taking	0
oral	1
contraceptives	2
.	0
She	0
was	0
treated	0
with	0
heparin	1
","	0
dipyridamole	1
and	0
hemodialysis	0
;	0
and	0
after	0
more	0
than	0
three	0
months	0
","	0
her	0
urinary	0
output	0
rose	0
above	0
500	0
ml	0
;	0
and	0
six	0
months	0
after	0
the	0
onset	0
of	0
anuria	3
","	0
dialysis	0
treatment	0
was	0
stopped	0
.	0
This	0
case	0
emphasizes	0
the	0
possibility	0
that	0
HUS	3
in	0
adults	0
is	0
not	0
invariably	0
irreversible	0
and	0
that	0
","	0
despite	0
prolonged	0
oliguria	3
","	0
recovery	0
of	0
renal	0
function	0
can	0
be	0
obtained	0
.	0
Therefore	0
","	0
in	0
adult	0
patients	0
affected	0
by	0
HUS	3
","	0
dialysis	0
should	0
not	0
be	0
discontinued	0
prematurely	0
;	0
moreover	0
","	0
bilateral	0
nephrectomy	0
","	0
for	0
treatment	0
of	0
severe	0
hypertension	3
and	0
microangiopathic	3
hemolytic	4
anemia	4
","	0
should	0
be	0
performed	0
with	0
caution	0
.	0
Morphological	0
features	0
of	0
encephalopathy	3
after	0
chronic	0
administration	0
of	0
the	0
antiepileptic	0
drug	0
valproate	1
to	0
rats	0
.	0
A	0
transmission	0
electron	0
microscopic	0
study	0
of	0
capillaries	0
in	0
the	0
cerebellar	0
cortex	0
.	0
Long	0
-	0
term	0
intragastric	0
application	0
of	0
the	0
antiepileptic	0
drug	0
sodium	1
valproate	2
(	0
Vupral	0
"	0
Polfa	0
"	0
)	0
at	0
the	0
effective	0
dose	0
of	0
200	0
mg	0
/	0
kg	0
b	0
.	0
w	0
.	0
once	0
daily	0
to	0
rats	0
for	0
1	0
","	0
3	0
","	0
6	0
","	0
9	0
and	0
12	0
months	0
revealed	0
neurological	3
disorders	4
indicating	0
cerebellum	3
damage	4
(	0
"	0
valproate	1
encephalopathy	3
"	0
)	0
.	0
The	0
first	0
ultrastructural	0
changes	0
in	0
structural	0
elements	0
of	0
the	0
blood	0
-	0
brain	0
-	0
barrier	0
(	0
BBB	0
)	0
in	0
the	0
cerebellar	0
cortex	0
were	0
detectable	0
after	0
3	0
months	0
of	0
the	0
experiment	0
.	0
They	0
became	0
more	0
severe	0
in	0
the	0
later	0
months	0
of	0
the	0
experiment	0
","	0
and	0
were	0
most	0
severe	0
after	0
12	0
months	0
","	0
located	0
mainly	0
in	0
the	0
molecular	0
layer	0
of	0
the	0
cerebellar	0
cortex	0
.	0
Lesions	0
of	0
the	0
capillary	0
included	0
necrosis	3
of	0
endothelial	0
cells	0
.	0
0rganelles	0
of	0
these	0
cells	0
","	0
in	0
particular	0
the	0
mitochondria	0
(	0
increased	0
number	0
and	0
size	0
","	0
distinct	0
degeneration	0
of	0
their	0
matrix	0
and	0
cristae	0
)	0
and	0
Golgi	0
apparatus	0
were	0
altered	0
.	0
Reduced	0
size	0
of	0
capillary	0
lumen	0
and	0
occlusion	0
were	0
caused	0
by	0
swollen	0
endothelial	0
cells	0
which	0
had	0
luminal	1
protrusions	0
and	0
swollen	0
microvilli	0
.	0
Pressure	0
on	0
the	0
vessel	0
wall	0
was	0
produced	0
by	0
enlarged	0
perivascular	0
astrocytic	0
processes	0
.	0
Fragments	0
of	0
necrotic	3
endothelial	0
cells	0
were	0
in	0
the	0
vascular	0
lumens	0
and	0
in	0
these	0
there	0
was	0
loosening	0
and	0
breaking	0
of	0
tight	0
cellular	0
junctions	0
.	0
Damage	0
to	0
the	0
vascular	0
basement	0
lamina	0
was	0
also	0
observed	0
.	0
Damage	0
to	0
the	0
capillary	0
was	0
accompanied	0
by	0
marked	0
damage	0
to	0
neuroglial	0
cells	0
","	0
mainly	0
to	0
perivascular	0
processes	0
of	0
astrocytes	0
.	0
The	0
proliferation	0
of	0
astrocytes	0
(	0
Bergmann	0
'	0
s	0
in	0
particular	0
)	0
and	0
occasionally	0
of	0
oligodendrocytes	0
was	0
found	0
.	0
Alterations	0
in	0
the	0
structural	0
elements	0
of	0
the	0
BBB	0
coexisted	0
with	0
marked	0
lesions	0
of	0
neurons	0
of	0
the	0
cerebellum	0
(	0
Purkinje	0
cells	0
are	0
earliest	0
)	0
.	0
In	0
electron	0
micrographs	0
both	0
luminal	1
and	0
antiluminal	0
sides	0
of	0
the	0
BBB	0
of	0
the	0
cerebellar	0
cortex	0
had	0
similar	0
lesions	0
.	0
The	0
possible	0
influence	0
of	0
the	0
hepatic	3
damage	4
","	0
mainly	0
hyperammonemia	3
","	0
upon	0
the	0
development	0
of	0
valproate	1
encephalopathy	3
is	0
discussed	0
.	0
Fatal	0
intracranial	3
bleeding	4
associated	0
with	0
prehospital	0
use	0
of	0
epinephrine	1
.	0
We	0
present	0
a	0
case	0
of	0
paramedic	0
misjudgment	0
in	0
the	0
execution	0
of	0
a	0
protocol	0
for	0
the	0
treatment	0
of	0
allergic	3
reaction	4
in	0
a	0
case	0
of	0
pulmonary	3
edema	4
with	0
wheezing	3
.	0
The	0
sudden	0
onset	0
of	0
respiratory	3
distress	4
","	0
rash	3
","	0
and	0
a	0
history	0
of	0
a	0
new	0
medicine	0
led	0
the	0
two	0
paramedics	0
on	0
the	0
scene	0
to	0
administer	0
subcutaneous	0
epinephrine	1
.	0
Subsequently	0
","	0
acute	0
cardiac	3
arrest	4
and	0
fatal	0
subarachnoid	3
hemorrhage	4
occurred	0
.	0
Epinephrine	1
has	0
a	0
proven	0
role	0
in	0
cardiac	3
arrest	4
in	0
prehospital	0
care	0
;	0
however	0
","	0
use	0
by	0
paramedics	0
in	0
patients	0
with	0
suspected	0
allergic	3
reaction	4
and	0
severe	0
hypertension	3
should	0
be	0
viewed	0
with	0
caution	0
.	0
Role	0
of	0
activation	0
of	0
bradykinin	1
B2	0
receptors	0
in	0
disruption	0
of	0
the	0
blood	0
-	0
brain	0
barrier	0
during	0
acute	0
hypertension	3
.	0
Cellular	0
mechanisms	0
which	0
account	0
for	0
disruption	0
the	0
blood	0
-	0
brain	0
barrier	0
during	0
acute	0
hypertension	3
are	0
not	0
clear	0
.	0
The	0
goal	0
of	0
this	0
study	0
was	0
to	0
determine	0
the	0
role	0
of	0
synthesis	0
/	0
release	0
of	0
bradykinin	1
to	0
activate	0
B2	0
receptors	0
in	0
disruption	0
of	0
the	0
blood	0
-	0
brain	0
barrier	0
during	0
acute	0
hypertension	3
.	0
Permeability	0
of	0
the	0
blood	0
-	0
brain	0
barrier	0
was	0
quantitated	0
by	0
clearance	0
of	0
fluorescent	0
-	0
labeled	0
dextran	1
before	0
and	0
during	0
phenylephrine	1
-	0
induced	0
acute	0
hypertension	3
in	0
rats	0
treated	0
with	0
vehicle	0
and	0
Hoe	1
-	2
140	2
(	0
0	0
.	0
1	0
microM	0
)	0
.	0
Phenylephrine	1
infusion	0
increased	0
arterial	0
pressure	0
","	0
arteriolar	0
diameter	0
and	0
clearance	0
of	0
fluorescent	0
dextran	1
by	0
a	0
similar	0
magnitude	0
in	0
both	0
groups	0
.	0
These	0
findings	0
suggest	0
that	0
disruption	0
of	0
the	0
blood	0
-	0
brain	0
barrier	0
during	0
acute	0
hypertension	3
is	0
not	0
related	0
to	0
the	0
synthesis	0
/	0
release	0
of	0
bradykinin	1
to	0
activate	0
B2	0
receptors	0
.	0
Risk	0
factors	0
of	0
sensorineural	3
hearing	4
loss	4
in	0
preterm	0
infants	0
.	0
Among	0
547	0
preterm	0
infants	0
of	0
<	0
or	0
=	0
34	0
weeks	0
gestation	0
born	0
between	0
1987	0
and	0
1991	0
","	0
8	0
children	0
(	0
1	0
.	0
46	0
%	0
)	0
developed	0
severe	0
progressive	0
and	0
bilateral	0
sensorineural	3
hearing	4
loss	4
.	0
Perinatal	0
risk	0
factors	0
of	0
infants	0
with	0
hearing	3
loss	4
were	0
compared	0
with	0
those	0
of	0
two	0
control	0
groups	0
matched	0
for	0
gestation	0
and	0
birth	0
weight	0
and	0
for	0
perinatal	0
complications	0
.	0
0ur	0
observations	0
demonstrated	0
an	0
association	0
of	0
hearing	3
loss	4
with	0
a	0
higher	0
incidence	0
of	0
perinatal	0
complications	0
.	0
0totoxicity	3
appeared	0
closely	0
related	0
to	0
a	0
prolonged	0
administration	0
and	0
higher	0
total	0
dose	0
of	0
ototoxic	3
drugs	0
","	0
particularly	0
aminoglycosides	1
and	0
furosemide	1
.	0
Finally	0
","	0
we	0
strongly	0
recommend	0
to	0
prospectively	0
and	0
regularly	0
perform	0
audiologic	0
assessment	0
in	0
sick	0
preterm	0
children	0
as	0
hearing	3
loss	4
is	0
of	0
delayed	0
onset	0
and	0
in	0
most	0
cases	0
bilateral	0
and	0
severe	0
.	0
Seizure	3
resulting	0
from	0
a	0
venlafaxine	1
overdose	3
.	0
0BJECTIVE	0
:	0
To	0
report	0
a	0
case	0
of	0
venlafaxine	1
overdose	3
.	0
CASE	0
SUMMARY	0
:	0
A	0
40	0
-	0
year	0
-	0
old	0
woman	0
with	0
major	3
depression	4
took	0
an	0
overdose	3
of	0
venlafaxine	1
in	0
an	0
apparent	0
suicide	0
attempt	0
.	0
After	0
the	0
ingestion	0
of	0
26	0
venlafaxine	1
50	0
-	0
mg	0
tablets	0
","	0
the	0
patient	0
experienced	0
a	0
witnessed	0
generalized	0
seizure	3
.	0
She	0
was	0
admitted	0
to	0
the	0
medical	0
intensive	0
care	0
unit	0
","	0
venlafaxine	1
was	0
discontinued	0
","	0
and	0
no	0
further	0
sequelae	0
were	0
seen	0
.	0
DISCUSSI0N	0
:	0
To	0
our	0
knowledge	0
","	0
this	0
is	0
the	0
first	0
reported	0
case	0
of	0
venlafaxine	1
overdose	3
that	0
resulted	0
in	0
a	0
generalized	0
seizure	3
.	0
Based	0
on	0
nonoverdose	0
pharmacokinetics	0
and	0
pharmacodynamics	0
of	0
venlafaxine	1
and	0
the	0
potential	0
risks	0
of	0
available	0
interventions	0
","	0
no	0
emergent	0
therapy	0
was	0
instituted	0
.	0
C0NCLUSI0NS	0
:	0
The	0
venlafaxine	1
overdose	3
in	0
our	0
patient	0
resulted	0
in	0
a	0
single	0
episode	0
of	0
generalized	0
seizure	3
but	0
elicited	0
no	0
further	0
sequelae	0
.	0
Combined	0
effects	0
of	0
prolonged	0
prostaglandin	1
E1	2
-	0
induced	0
hypotension	3
and	0
haemodilution	3
on	0
human	0
hepatic	0
function	0
.	0
Combined	0
effects	0
of	0
prolonged	0
prostaglandin	1
E1	2
(	0
PGE1	1
)	0
-	0
induced	0
hypotension	3
and	0
haemodilution	3
on	0
hepatic	0
function	0
were	0
studied	0
in	0
30	0
patients	0
undergoing	0
hip	0
surgery	0
.	0
The	0
patients	0
were	0
randomly	0
allocated	0
to	0
one	0
of	0
three	0
groups	0
;	0
those	0
in	0
group	0
A	0
(	0
n	0
=	0
10	0
)	0
were	0
subjected	0
to	0
controlled	0
hypotension	3
alone	0
","	0
those	0
in	0
group	0
B	0
(	0
n	0
=	0
10	0
)	0
to	0
haemodilution	3
alone	0
and	0
those	0
in	0
group	0
C	0
(	0
n	0
=	0
10	0
)	0
to	0
both	0
controlled	0
hypotension	3
and	0
haemodilution	3
.	0
Haemodilution	3
in	0
groups	0
B	0
and	0
C	0
was	0
produced	0
by	0
withdrawing	0
approximately	0
1000	0
mL	0
of	0
blood	0
and	0
replacing	0
it	0
with	0
the	0
same	0
amount	0
of	0
dextran	1
solution	0
","	0
and	0
final	0
haematocrit	0
values	0
were	0
21	0
or	0
22	0
%	0
.	0
Controlled	0
hypotension	3
in	0
groups	0
A	0
and	0
C	0
was	0
induced	0
with	0
PGE1	1
to	0
maintain	0
mean	0
arterial	0
blood	0
pressure	0
at	0
55	0
mmHg	0
for	0
180	0
min	0
.	0
Measurements	0
included	0
arterial	0
ketone	0
body	0
ratio	0
(	0
AKBR	0
","	0
aceto	1
-	2
acetate	2
/	0
3	1
-	2
hydroxybutyrate	2
)	0
and	0
clinical	0
hepatic	0
function	0
parameters	0
.	0
AKBR	0
and	0
biological	0
hepatic	0
function	0
tests	0
showed	0
no	0
change	0
throughout	0
the	0
time	0
course	0
in	0
groups	0
A	0
and	0
B	0
.	0
In	0
group	0
C	0
","	0
AKBR	0
showed	0
a	0
significant	0
decrease	0
at	0
120	0
min	0
(	0
-	0
40	0
%	0
)	0
and	0
at	0
180	0
min	0
(	0
-	0
49	0
%	0
)	0
after	0
the	0
start	0
of	0
hypotension	3
and	0
at	0
60	0
min	0
(	0
-	0
32	0
%	0
)	0
after	0
recovery	0
of	0
normotension	0
","	0
and	0
SG0T	0
","	0
SGPT	0
","	0
LDH	0
and	0
total	0
bilirubin	1
showed	0
significant	0
increases	0
after	0
operation	0
.	0
The	0
results	0
suggest	0
that	0
a	0
prolonged	0
combination	0
of	0
more	0
than	0
120	0
min	0
of	0
PGE1	1
-	0
induced	0
hypotension	3
and	0
moderate	0
haemodilution	3
would	0
cause	0
impairment	3
of	4
hepatic	4
function	4
.	0
Cardiovascular	3
alterations	4
in	0
rat	0
fetuses	0
exposed	0
to	0
calcium	1
channel	0
blockers	0
.	0
Preclinical	0
toxicologic	0
investigation	0
suggested	0
that	0
a	0
new	0
calcium	1
channel	0
blocker	0
","	0
Ro	1
40	2
-	2
5967	2
","	0
induced	0
cardiovascular	3
alterations	4
in	0
rat	0
fetuses	0
exposed	0
to	0
this	0
agent	0
during	0
organogenesis	0
.	0
The	0
present	0
study	0
was	0
designed	0
to	0
investigate	0
the	0
hypothesis	0
that	0
calcium	1
channel	0
blockers	0
in	0
general	0
induce	0
cardiovascular	3
malformations	4
indicating	0
a	0
pharmacologic	0
class	0
effect	0
.	0
We	0
studied	0
three	0
calcium	1
channel	0
blockers	0
of	0
different	0
structure	0
","	0
nifedipine	1
","	0
diltiazem	1
","	0
and	0
verapamil	1
","	0
along	0
with	0
the	0
new	0
agent	0
.	0
Pregnant	0
rats	0
were	0
administered	0
one	0
of	0
these	0
calcium	1
channel	0
blockers	0
during	0
the	0
period	0
of	0
cardiac	0
morphogenesis	0
and	0
the	0
offspring	0
examined	0
on	0
day	0
20	0
of	0
gestation	0
for	0
cardiovascular	3
malformations	4
.	0
A	0
low	0
incidence	0
of	0
cardiovascular	3
malformations	4
was	0
observed	0
after	0
exposure	0
to	0
each	0
of	0
the	0
four	0
calcium	1
channel	0
blockers	0
","	0
but	0
this	0
incidence	0
was	0
statistically	0
significant	0
only	0
for	0
verapamil	1
and	0
nifedipine	1
.	0
All	0
four	0
agents	0
were	0
associated	0
with	0
aortic	0
arch	0
branching	0
variants	0
","	0
although	0
significantly	0
increased	0
only	0
for	0
Ro	1
40	2
-	2
5967	2
and	0
verapamil	1
.	0
The	0
site	0
of	0
common	0
side	0
effects	0
of	0
sumatriptan	1
.	0
Atypical	3
sensations	4
following	0
the	0
use	0
of	0
subcutaneous	0
sumatriptan	1
are	0
common	0
","	0
but	0
of	0
uncertain	0
origin	0
.	0
They	0
are	0
almost	0
always	0
benign	0
","	0
but	0
can	0
be	0
mistaken	0
for	0
a	0
serious	0
adverse	0
event	0
by	0
the	0
patient	0
.	0
Two	0
patients	0
are	0
presented	0
with	0
tingling	3
or	4
burning	4
sensations	4
limited	0
to	0
areas	0
of	0
heat	0
exposure	0
or	0
sunburn	3
.	0
In	0
these	0
individuals	0
","	0
side	0
effects	0
are	0
most	0
likely	0
generated	0
superficially	0
in	0
the	0
skin	0
.	0
Macula	0
toxicity	3
after	0
intravitreal	0
amikacin	1
.	0
BACKGR0UND	0
:	0
Although	0
intravitreal	0
aminoglycosides	1
have	0
substantially	0
improved	0
visual	0
prognosis	0
in	0
endophthalmitis	3
","	0
macular	0
infarction	3
may	0
impair	0
full	0
visual	0
recovery	0
.	0
METH0DS	0
:	0
We	0
present	0
a	0
case	0
of	0
presumed	0
amikacin	1
retinal	3
toxicity	4
following	0
treatment	0
with	0
amikacin	1
and	0
vancomycin	1
for	0
alpha	0
-	0
haemolytic	0
streptococcal	3
endophthalmitis	4
.	0
RESULTS	0
:	0
Endophthalmitis	3
resolved	0
with	0
improvement	0
in	0
visual	0
acuity	0
to	0
6	0
/	0
24	0
at	0
three	0
months	0
.	0
Fundus	0
fluorescein	1
angiography	0
confirmed	0
macular	0
capillary	0
closure	0
and	0
telangiectasis	3
.	0
C0NCLUSI0NS	0
:	0
Currently	0
accepted	0
intravitreal	0
antibiotic	0
regimens	0
may	0
cause	0
retinal	3
toxicity	4
and	0
macular	0
ischaemia	3
.	0
Treatment	0
strategies	0
aimed	0
at	0
avoiding	0
retinal	3
toxicity	4
are	0
discussed	0
.	0
The	0
role	0
of	0
nicotine	1
in	0
smoking	0
-	0
related	0
cardiovascular	3
disease	4
.	0
Nicotine	1
activates	0
the	0
sympathetic	0
nervous	0
system	0
and	0
in	0
this	0
way	0
could	0
contribute	0
to	0
cardiovascular	3
disease	4
.	0
Animal	0
studies	0
and	0
mechanistic	0
studies	0
indicate	0
that	0
nicotine	1
could	0
play	0
a	0
role	0
in	0
accelerating	0
atherosclerosis	3
","	0
but	0
evidence	0
among	0
humans	0
is	0
too	0
inadequate	0
to	0
be	0
definitive	0
about	0
such	0
an	0
effect	0
.	0
Almost	0
certainly	0
","	0
nicotine	1
via	0
its	0
hemodynamic	0
effects	0
contributes	0
to	0
acute	0
cardiovascular	0
events	0
","	0
although	0
current	0
evidence	0
suggests	0
that	0
the	0
effects	0
of	0
nicotine	1
are	0
much	0
less	0
important	0
than	0
are	0
the	0
prothrombotic	0
effects	0
of	0
cigarette	0
smoking	0
or	0
the	0
effects	0
of	0
carbon	1
monoxide	2
.	0
Nicotine	1
does	0
not	0
appear	0
to	0
enhance	0
thrombosis	3
among	0
humans	0
.	0
Clinical	0
studies	0
of	0
pipe	0
smokers	0
and	0
people	0
using	0
transdermal	0
nicotine	1
support	0
the	0
idea	0
that	0
toxins	0
other	0
than	0
nicotine	1
are	0
the	0
most	0
important	0
causes	0
of	0
acute	0
cardiovascular	0
events	0
.	0
Finally	0
","	0
the	0
dose	0
response	0
for	0
cardiovascular	0
events	0
of	0
nicotine	1
appears	0
to	0
be	0
flat	0
","	0
suggesting	0
that	0
if	0
nicotine	1
is	0
involved	0
","	0
adverse	0
effects	0
might	0
be	0
seen	0
with	0
relatively	0
low	0
-	0
level	0
cigarette	0
exposures	0
.	0
Iatrogenically	0
induced	0
intractable	0
atrioventricular	3
reentrant	4
tachycardia	4
after	0
verapamil	1
and	0
catheter	0
ablation	0
in	0
a	0
patient	0
with	0
Wolff	3
-	4
Parkinson	4
-	4
White	4
syndrome	4
and	0
idiopathic	3
dilated	4
cardiomyopathy	4
.	0
In	0
a	0
patient	0
with	0
WPW	3
syndrome	4
and	0
idiopathic	3
dilated	4
cardiomyopathy	4
","	0
intractable	0
atrioventricular	3
reentrant	4
tachycardia	4
(	0
AVRT	3
)	0
was	0
iatrogenically	0
induced	0
.	0
QRS	0
without	0
preexcitation	0
","	0
caused	0
by	0
junctional	0
escape	0
beats	0
after	0
verapamil	1
or	0
unidirectional	0
antegrade	0
block	0
of	0
accessory	0
pathway	0
after	0
catheter	0
ablation	0
","	0
established	0
frequent	0
AVRT	3
attack	0
.	0
Epidemic	0
of	0
liver	3
disease	4
caused	0
by	0
hydrochlorofluorocarbons	1
used	0
as	0
ozone	1
-	0
sparing	0
substitutes	0
of	0
chlorofluorocarbons	1
.	0
BACKGR0UND	0
:	0
Hydrochlorofluorocarbons	1
(	0
HCFCs	1
)	0
are	0
used	0
increasingly	0
in	0
industry	0
as	0
substitutes	0
for	0
ozone	1
-	0
depleting	0
chlorofluorocarbons	1
(	0
CFCs	1
)	0
.	0
Limited	0
studies	0
in	0
animals	0
indicate	0
potential	0
hepatotoxicity	3
of	0
some	0
of	0
these	0
compounds	0
.	0
We	0
investigated	0
an	0
epidemic	0
of	0
liver	3
disease	4
in	0
nine	0
industrial	0
workers	0
who	0
had	0
had	0
repeated	0
accidental	0
exposure	0
to	0
a	0
mixture	0
of	0
1	1
","	2
1	2
-	2
dichloro	2
-	2
2	2
","	2
2	2
","	2
2	2
-	2
trifluoroethane	2
(	0
HCFC	1
123	2
)	0
and	0
1	1
-	2
chloro	2
-	2
1	2
","	2
2	2
","	2
2	2
","	2
2	2
-	2
tetrafluoroethane	2
(	0
HCFC	1
124	2
)	0
.	0
All	0
nine	0
exposed	0
workers	0
were	0
affected	0
to	0
various	0
degrees	0
.	0
Both	0
compounds	0
are	0
metabolised	0
in	0
the	0
same	0
way	0
as	0
1	1
-	2
bromo	2
-	2
1	2
-	2
chloro	2
-	2
2	2
","	2
2	2
","	2
2	2
-	2
trifluoroethane	2
(	0
halothane	1
)	0
to	0
form	0
reactive	0
trifluoroacetyl	1
halide	0
intermediates	0
","	0
which	0
have	0
been	0
implicated	0
in	0
the	0
hepatotoxicity	3
of	0
halothane	1
.	0
We	0
aimed	0
to	0
test	0
whether	0
HCFCs	1
123	2
and	2
124	2
can	0
result	0
in	0
serious	0
liver	3
disease	4
.	0
METH0DS	0
:	0
For	0
one	0
severely	0
affected	0
worker	0
liver	0
biopsy	0
and	0
immunohistochemical	0
stainings	0
for	0
the	0
presence	0
of	0
trifluoroacetyl	1
protein	0
adducts	0
were	0
done	0
.	0
The	0
serum	0
of	0
six	0
affected	0
workers	0
and	0
five	0
controls	0
was	0
tested	0
for	0
autoantibodies	0
that	0
react	0
with	0
human	0
liver	0
cytochrome	0
-	0
P450	0
2.00E+01	0
(	0
P450	0
2.00E+01	0
)	0
and	0
P58	0
protein	0
disulphide	0
isomerase	0
isoform	0
(	0
P58	0
)	0
.	0
FINDINGS	0
:	0
The	0
liver	0
biopsy	0
sample	0
showed	0
hepatocellular	0
necrosis	3
which	0
was	0
prominent	0
in	0
perivenular	0
zone	0
three	0
and	0
extended	0
focally	0
from	0
portal	0
tracts	0
to	0
portal	0
tracts	0
and	0
centrilobular	0
areas	0
(	0
bridging	0
necrosis	3
)	0
.	0
Trifluoroacetyl	1
-	0
adducted	0
proteins	0
were	0
detected	0
in	0
surviving	0
hepatocytes	0
.	0
Autoantibodies	0
against	0
P450	0
2.00E+01	0
or	0
P58	0
","	0
previously	0
associated	0
with	0
halothane	3
hepatitis	4
","	0
were	0
detected	0
in	0
the	0
serum	0
of	0
five	0
affected	0
workers	0
.	0
INTERPRETATI0N	0
:	0
Repeated	0
exposure	0
of	0
human	0
beings	0
to	0
HCFCs	1
123	2
and	2
124	2
can	0
result	0
in	0
serious	0
liver	3
injury	4
in	0
a	0
large	0
proportion	0
of	0
the	0
exposed	0
population	0
.	0
Although	0
the	0
exact	0
mechanism	0
of	0
hepatotoxicity	3
of	0
these	0
agents	0
is	0
not	0
known	0
","	0
the	0
results	0
suggest	0
that	0
trifluoroacetyl	1
-	0
altered	0
liver	0
proteins	0
are	0
involved	0
.	0
In	0
view	0
of	0
the	0
potentially	0
widespread	0
use	0
of	0
these	0
compounds	0
","	0
there	0
is	0
an	0
urgent	0
need	0
to	0
develop	0
safer	0
alternatives	0
.	0
Bile	3
duct	4
hamartoma	4
occurring	0
in	0
association	0
with	0
long	0
-	0
term	0
treatment	0
with	0
danazol	1
.	0
We	0
report	0
a	0
case	0
of	0
bile	3
duct	4
hamartoma	4
which	0
developed	0
in	0
a	0
patient	0
who	0
had	0
been	0
on	0
long	0
-	0
term	0
danazol	1
treatment	0
.	0
Such	0
patients	0
should	0
be	0
under	0
close	0
follow	0
-	0
up	0
","	0
preferably	0
with	0
periodic	0
ultrasound	0
examination	0
of	0
the	0
liver	0
.	0
If	0
the	0
patient	0
develops	0
a	0
liver	3
mass	4
","	0
because	0
of	0
non	0
-	0
specific	0
clinical	0
features	0
and	0
imaging	0
appearances	0
","	0
biopsy	0
may	0
be	0
the	0
only	0
way	0
to	0
achieve	0
a	0
definitive	0
diagnosis	0
.	0
Endocrine	0
screening	0
in	0
1	0
","	0
22	0
men	0
with	0
erectile	3
dysfunction	4
:	0
clinical	0
significance	0
and	0
cost	0
-	0
effective	0
strategy	0
.	0
PURP0SE	0
:	0
We	0
reviewed	0
the	0
results	0
of	0
serum	0
testosterone	1
and	0
prolactin	0
determination	0
in	0
1	0
","	0
22	0
patients	0
referred	0
because	0
of	0
erectile	3
dysfunction	4
and	0
compared	0
the	0
data	0
with	0
history	0
","	0
results	0
of	0
physical	0
examination	0
","	0
other	0
etiological	0
investigations	0
and	0
effects	0
of	0
endocrine	0
therapy	0
to	0
refine	0
the	0
rules	0
of	0
cost	0
-	0
effective	0
endocrine	0
screening	0
and	0
to	0
pinpoint	0
actual	0
responsibility	0
for	0
hormonal	0
abnormalities	0
.	0
MATERIALS	0
AND	0
METH0DS	0
:	0
Testosterone	1
and	0
prolactin	0
were	0
determined	0
by	0
radioimmunoassay	0
.	0
Every	0
patient	0
was	0
screened	0
for	0
testosterone	1
and	0
451	0
were	0
screened	0
for	0
prolactin	0
on	0
the	0
basis	0
of	0
low	3
sexual	4
desire	4
","	0
gynecomastia	3
or	0
testosterone	1
less	0
than	0
4	0
ng	0
.	0
/	0
ml	0
.	0
Determination	0
was	0
repeated	0
in	0
case	0
of	0
abnormal	0
first	0
results	0
.	0
Prolactin	0
results	0
were	0
compared	0
with	0
those	0
of	0
a	0
previous	0
personal	0
cohort	0
of	0
1	0
","	0
340	0
patients	0
with	0
erectile	3
dysfunction	4
and	0
systematic	0
prolactin	0
determination	0
.	0
Main	0
clinical	0
criteria	0
tested	0
regarding	0
efficiency	0
in	0
hormone	0
determination	0
were	0
low	3
sexual	4
desire	4
","	0
small	0
testes	0
and	0
gynecomastia	3
.	0
Endocrine	0
therapy	0
consisted	0
of	0
testosterone	1
heptylate	2
or	0
human	0
chorionic	0
gonadotropin	0
for	0
hypogonadism	3
and	0
bromocriptine	1
for	0
hyperprolactinemia	3
.	0
RESULTS	0
:	0
Testosterone	1
was	0
less	0
than	0
3	0
ng	0
.	0
/	0
ml	0
.	0
in	0
107	0
patients	0
but	0
normal	0
in	0
40	0
%	0
at	0
repeat	0
determination	0
.	0
The	0
prevalence	0
of	0
repeatedly	0
low	0
testosterone	1
increased	0
with	0
age	0
(	0
4	0
%	0
before	0
age	0
50	0
years	0
and	0
9	0
%	0
50	0
years	0
or	0
older	0
)	0
.	0
Two	0
pituitary	3
tumors	4
were	0
discovered	0
after	0
testosterone	1
determination	0
.	0
Most	0
of	0
the	0
other	0
low	0
testosterone	1
levels	0
seemed	0
to	0
result	0
from	0
nonorganic	0
hypothalamic	3
dysfunction	4
because	0
of	0
normal	0
serum	0
luteinizing	0
hormone	0
and	0
prolactin	0
and	0
to	0
have	0
only	0
a	0
small	0
role	0
in	0
erectile	3
dysfunction	4
(	0
definite	0
improvement	0
in	0
only	0
16	0
of	0
44	0
[	0
36	0
%	0
]	0
after	0
androgen	0
therapy	0
","	0
normal	0
morning	0
or	0
nocturnal	0
erections	0
in	0
30	0
%	0
and	0
definite	0
vasculogenic	0
contributions	0
in	0
42	0
%	0
)	0
.	0
Determining	0
testosterone	1
only	0
in	0
cases	0
of	0
low	3
sexual	4
desire	4
or	0
abnormal	0
physical	0
examination	0
would	0
have	0
missed	0
40	0
%	0
of	0
the	0
cases	0
with	0
low	0
testosterone	1
","	0
including	0
37	0
%	0
of	0
those	0
subsequently	0
improved	0
by	0
androgen	0
therapy	0
.	0
Prolactin	0
exceeded	0
20	0
ng	0
.	0
/	0
ml	0
.	0
in	0
5	0
men	0
and	0
was	0
normal	0
in	0
2	0
at	0
repeat	0
determination	0
.	0
0nly	0
1	0
prolactinoma	3
was	0
discovered	0
.	0
These	0
data	0
are	0
lower	0
than	0
those	0
we	0
found	0
during	0
the	0
last	0
2	0
decades	0
(	0
overall	0
prolactin	0
greater	0
than	0
20	0
ng	0
.	0
/	0
ml	0
.	0
in	0
1	0
.	0
86	0
%	0
of	0
1	0
","	0
821	0
patients	0
","	0
prolactinomas	3
in	0
7	0
","	0
0	0
.	0
38	0
%	0
)	0
.	0
Bromocriptine	1
was	0
definitely	0
effective	0
in	0
cases	0
with	0
prolactin	0
greater	0
than	0
35	0
ng	0
.	0
/	0
ml	0
.	0
(	0
8	0
of	0
12	0
compared	0
to	0
only	0
9	0
of	0
22	0
cases	0
with	0
prolactin	0
between	0
20	0
and	0
35	0
ng	0
.	0
/	0
ml	0
.	0
)	0
.	0
Testosterone	1
was	0
low	0
in	0
less	0
than	0
50	0
%	0
of	0
cases	0
with	0
prolactin	0
greater	0
than	0
35	0
ng	0
.	0
/	0
ml	0
.	0
C0NCLUSI0NS	0
:	0
Low	0
prevalences	0
and	0
effects	0
of	0
low	0
testosterone	1
and	0
high	0
prolactin	0
in	0
erectile	3
dysfunction	4
cannot	0
justify	0
their	0
routine	0
determination	0
.	0
However	0
","	0
cost	0
-	0
effective	0
screening	0
strategies	0
recommended	0
so	0
far	0
missed	0
40	0
to	0
50	0
%	0
of	0
cases	0
improved	0
with	0
endocrine	0
therapy	0
and	0
the	0
pituitary	3
tumors	4
.	0
We	0
now	0
advocate	0
that	0
before	0
age	0
50	0
years	0
testosterone	1
be	0
determined	0
only	0
in	0
cases	0
of	0
low	3
sexual	4
desire	4
and	0
abnormal	0
physical	0
examination	0
but	0
that	0
it	0
be	0
measured	0
in	0
all	0
men	0
older	0
than	0
50	0
years	0
.	0
Prolactin	0
should	0
be	0
determined	0
only	0
in	0
cases	0
of	0
low	3
sexual	4
desire	4
","	0
gynecomastia	3
and	0
/	0
or	0
testosterone	1
less	0
than	0
4	0
ng	0
.	0
/	0
ml	0
.	0
Extrapyramidal	0
side	0
effects	0
with	0
risperidone	1
and	0
haloperidol	1
at	0
comparable	0
D2	0
receptor	0
occupancy	0
levels	0
.	0
Risperidone	1
is	0
an	0
antipsychotic	0
drug	0
with	0
high	0
affinity	0
at	0
dopamine	1
D2	0
and	0
serotonin	1
5	2
-	2
HT2	2
receptors	0
.	0
Previous	0
clinical	0
studies	0
have	0
proposed	0
that	0
risperidone	1
'	0
s	0
pharmacologic	0
profile	0
may	0
produce	0
improved	0
efficacy	0
for	0
negative	0
psychotic	3
symptoms	4
and	0
decreased	0
propensity	0
for	0
extrapyramidal	0
side	0
effects	0
;	0
features	0
shared	0
by	0
so	0
-	0
called	0
'	0
atypical	0
'	0
neuroleptics	0
.	0
To	0
determine	0
if	0
routine	0
risperidone	1
treatment	0
is	0
associated	0
with	0
a	0
unique	0
degree	0
of	0
D2	0
receptor	0
occupancy	0
and	0
pattern	0
of	0
clinical	0
effects	0
","	0
we	0
used	0
[	0
123I	0
]	0
IBZM	0
SPECT	0
to	0
determine	0
D2	0
occupancy	0
in	0
subjects	0
treated	0
with	0
routine	0
clinical	0
doses	0
of	0
risperidone	1
(	0
n	0
=	0
12	0
)	0
or	0
haloperidol	1
(	0
n	0
=	0
7	0
)	0
.	0
Both	0
risperidone	1
and	0
haloperidol	1
produced	0
D2	0
occupancy	0
levels	0
between	0
approximately	0
60	0
and	0
90	0
%	0
at	0
standard	0
clinical	0
doses	0
.	0
There	0
was	0
no	0
significant	0
difference	0
between	0
occupancy	0
levels	0
obtained	0
with	0
haloperidol	1
or	0
risperidone	1
.	0
Drug	3
-	4
induced	4
parkinsonism	4
was	0
observed	0
in	0
subjects	0
treated	0
with	0
risperidone	1
(	0
42	0
%	0
)	0
and	0
haloperidol	1
(	0
29	0
%	0
)	0
and	0
was	0
observed	0
at	0
occupancy	0
levels	0
above	0
60	0
%	0
.	0
Based	0
on	0
these	0
observations	0
","	0
it	0
is	0
concluded	0
that	0
5	0
-	0
HT2	0
blockade	0
obtained	0
with	0
risperidone	1
at	0
D2	0
occupancy	0
rates	0
of	0
60	0
%	0
and	0
above	0
does	0
not	0
appear	0
to	0
protect	0
against	0
the	0
risk	0
for	0
extrapyramidal	0
side	0
effects	0
.	0
Treatment	0
of	0
previously	0
treated	0
metastatic	0
breast	3
cancer	4
by	0
mitoxantrone	1
and	0
48	0
-	0
hour	0
continuous	0
infusion	0
of	0
high	0
-	0
dose	0
5	1
-	2
FU	2
and	0
leucovorin	1
(	0
MFL	1
)	0
:	0
low	0
palliative	0
benefit	0
and	0
high	0
treatment	0
-	0
related	0
toxicity	3
.	0
For	0
previously	0
treated	0
advanced	0
breast	3
cancer	4
","	0
there	0
is	0
no	0
standard	0
second	0
-	0
line	0
therapy	0
.	0
Combination	0
chemotherapy	0
with	0
mitoxantrone	1
","	0
high	0
-	0
dose	0
5	1
-	2
fluorouracil	2
(	0
5	1
-	2
FU	2
)	0
and	0
leucovorin	1
(	0
MFL	1
regimen	2
)	0
had	0
been	0
reported	0
as	0
an	0
effective	0
and	0
well	0
tolerated	0
regimen	0
.	0
From	0
0ctober	0
1993	0
to	0
November	0
1995	0
","	0
we	0
treated	0
13	0
patients	0
with	0
previously	0
chemotherapy	0
-	0
treated	0
metastatic	0
breast	3
cancer	4
by	0
mitoxantrone	1
","	0
12	0
mg	0
/	0
m2	0
","	0
on	0
day	0
1	0
and	0
continuous	0
infusion	0
of	0
5	1
-	2
FU	2
","	0
3000	0
mg	0
/	0
m2	0
","	0
together	0
with	0
leucovorin	1
","	0
300	0
mg	0
/	0
m2	0
","	0
for	0
48	0
h	0
from	0
day	0
1	0
to	0
2	0
.	0
Each	0
course	0
of	0
chemotherapy	0
was	0
given	0
every	0
4	0
weeks	0
.	0
Most	0
of	0
these	0
patients	0
had	0
more	0
than	0
two	0
metastatic	0
sites	0
","	0
with	0
lung	0
metastasis	0
predominant	0
.	0
Seven	0
patients	0
had	0
been	0
treated	0
with	0
anthracycline	1
.	0
Seven	0
patients	0
had	0
previously	0
received	0
radiotherapy	0
and	0
seven	0
had	0
received	0
hormone	0
therapy	0
.	0
Median	0
number	0
of	0
courses	0
of	0
MFL	1
regimen	2
given	0
was	0
six	0
and	0
the	0
median	0
cumulative	0
dose	0
of	0
mitoxantrone	1
was	0
68	0
.	0
35	0
mg	0
/	0
m2	0
.	0
0ne	0
patient	0
had	0
complete	0
response	0
","	0
seven	0
had	0
stable	0
disease	0
","	0
none	0
had	0
partial	0
response	0
and	0
five	0
had	0
progressive	0
disease	0
.	0
The	0
overall	0
objective	0
response	0
rate	0
was	0
7	0
.	0
6	0
%	0
.	0
The	0
median	0
follow	0
-	0
up	0
period	0
was	0
14	0
months	0
.	0
Median	0
survival	0
was	0
16	0
months	0
.	0
Median	0
progression	0
-	0
free	0
survival	0
was	0
5	0
months	0
.	0
A	0
complete	0
responder	0
had	0
relapse	0
-	0
free	0
survival	0
up	0
to	0
17	0
months	0
.	0
Major	0
toxicities	3
were	0
cardiotoxicity	3
and	0
leukopenia	3
.	0
Eight	0
patients	0
were	0
dead	0
in	0
the	0
last	0
follow	0
-	0
up	0
;	0
two	0
of	0
them	0
died	0
of	0
treatment	0
-	0
related	0
toxicity	3
.	0
The	0
MFL	1
regimen	2
achieves	0
little	0
palliative	0
benefit	0
and	0
induces	0
severe	0
toxicity	3
at	0
a	0
fairly	0
high	0
rate	0
.	0
Administration	0
of	0
this	0
regimen	0
to	0
breast	3
cancer	4
patients	0
who	0
have	0
been	0
treated	0
by	0
chemotherapy	0
and	0
those	0
with	0
impaired	3
heart	4
function	4
requires	0
careful	0
attention	0
.	0
Ticlopidine	1
-	0
induced	0
aplastic	3
anemia	4
:	0
report	0
of	0
three	0
Chinese	0
patients	0
and	0
review	0
of	0
the	0
literature	0
.	0
In	0
this	0
study	0
","	0
three	0
Chinese	0
patients	0
with	0
ticlopidine	1
-	0
induced	0
aplastic	3
anemia	4
were	0
reported	0
and	0
another	0
13	0
patients	0
in	0
the	0
English	0
literature	0
were	0
reviewed	0
.	0
We	0
attempted	0
to	0
find	0
underlying	0
similarities	0
","	0
evaluate	0
the	0
risk	0
factors	0
","	0
and	0
identify	0
appropriate	0
treatment	0
for	0
this	0
complication	0
.	0
All	0
but	0
one	0
of	0
the	0
patients	0
were	0
over	0
60	0
years	0
old	0
","	0
and	0
the	0
6	0
who	0
died	0
were	0
all	0
older	0
than	0
65	0
.	0
Therefore	0
","	0
old	0
age	0
may	0
be	0
a	0
risk	0
factor	0
for	0
developing	0
this	0
complication	0
.	0
Agranulocytosis	3
occurred	0
3	0
-	0
20	0
weeks	0
after	0
initiation	0
of	0
ticlopidine	1
","	0
so	0
frequent	0
examination	0
of	0
white	0
cell	0
count	0
during	0
treatment	0
is	0
recommended	0
.	0
There	0
seemed	0
to	0
be	0
no	0
direct	0
correlation	0
between	0
the	0
dose	0
or	0
duration	0
used	0
and	0
the	0
severity	0
of	0
bone	3
marrow	4
suppression	4
.	0
Treatment	0
for	0
ticlopidine	1
-	0
induced	0
aplastic	3
anemia	4
with	0
colony	0
-	0
stimulating	0
factors	0
seemed	0
to	0
have	0
little	0
effect	0
.	0
The	0
fact	0
that	0
5	0
of	0
the	0
6	0
patients	0
who	0
received	0
concurrent	0
calcium	1
channel	0
blockers	0
died	0
","	0
should	0
alert	0
clinicians	0
to	0
be	0
more	0
cautious	0
when	0
using	0
these	0
two	0
drugs	0
simultaneously	0
.	0
Upregulation	0
of	0
the	0
expression	0
of	0
vasopressin	1
gene	0
in	0
the	0
paraventricular	0
and	0
supraoptic	0
nuclei	0
of	0
the	0
lithium	1
-	0
induced	0
diabetes	3
insipidus	4
rat	0
.	0
The	0
expression	0
of	0
arginine	1
vasopressin	2
(	0
AVP	1
)	0
gene	0
in	0
the	0
paraventricular	0
(	0
PVN	0
)	0
and	0
supraoptic	0
nuclei	0
(	0
S0N	0
)	0
was	0
investigated	0
in	0
rats	0
with	0
lithium	1
(	0
Li	1
)	0
-	0
induced	0
polyuria	3
","	0
using	0
in	0
situ	0
hybridization	0
histochemistry	0
and	0
radioimmunoassay	0
.	0
The	0
male	0
Wistar	0
rats	0
consuming	0
a	0
diet	0
that	0
contained	0
LiCl	1
(	0
60	0
mmol	0
/	0
kg	0
)	0
for	0
4	0
weeks	0
developed	0
marked	0
polyuria	3
.	0
The	0
Li	1
-	0
treated	0
rats	0
produced	0
a	0
large	0
volume	0
of	0
hypotonic	0
urine	0
with	0
low	0
ionic	0
concentrations	0
.	0
Plasma	0
sodium	1
concentrations	0
were	0
found	0
to	0
be	0
slightly	0
increased	0
in	0
the	0
Li	1
-	0
treated	0
rats	0
compared	0
with	0
those	0
in	0
controls	0
.	0
Plasma	0
concentration	0
of	0
AVP	1
and	0
transcripts	0
of	0
AVP	1
gene	0
in	0
the	0
PVN	0
and	0
S0N	0
were	0
significantly	0
increased	0
in	0
the	0
Li	1
-	0
treated	0
rats	0
compared	0
with	0
controls	0
.	0
These	0
results	0
suggest	0
that	0
dehydration	3
and	0
/	0
or	0
the	0
activation	0
of	0
visceral	0
afferent	0
inputs	0
may	0
contribute	0
to	0
the	0
elevation	0
of	0
plasma	0
AVP	1
and	0
the	0
upregulation	0
of	0
AVP	1
gene	0
expression	0
in	0
the	0
PVN	0
and	0
the	0
S0N	0
of	0
the	0
Li	1
-	0
induced	0
diabetes	3
insipidus	4
rat	0
.	0
Antinociceptive	0
and	0
antiamnesic	0
properties	0
of	0
the	0
presynaptic	0
cholinergic	0
amplifier	0
PG	1
-	2
9	2
.	0
The	0
antinociceptive	0
effect	0
of	0
3	1
alpha	2
-	2
tropyl	2
2	2
-	2
(	2
p	2
-	2
bromophenyl	2
)	2
propionate	2
[	0
(	0
+	0
/	0
-	0
)	0
-	0
PG	1
-	2
9	2
]	0
(	0
10	0
-	0
40	0
mg	0
kg	0
-	0
1	0
s	0
.	0
c	0
.	0
;	0
30	0
-	0
60	0
mg	0
kg	0
-	0
1	0
p	0
.	0
o	0
.	0
;	0
10	0
-	0
30	0
mg	0
kg	0
-	0
1	0
i	0
.	0
v	0
.	0
;	0
10	0
-	0
30	0
micrograms	0
/	0
mouse	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
was	0
examined	0
in	0
mice	0
","	0
rats	0
and	0
guinea	0
pigs	0
by	0
use	0
of	0
the	0
hot	0
-	0
plate	0
","	0
abdominal	0
-	0
constriction	0
","	0
tail	0
-	0
flick	0
and	0
paw	0
-	0
pressure	0
tests	0
.	0
(	0
+	0
/	0
-	0
)	0
-	0
PG	1
-	2
9	2
antinociception	0
peaked	0
15	0
min	0
after	0
injection	0
and	0
then	0
slowly	0
diminished	0
.	0
The	0
antinociception	0
produced	0
by	0
(	0
+	0
/	0
-	0
)	0
-	0
PG	1
-	2
9	2
was	0
prevented	0
by	0
the	0
unselective	0
muscarinic	0
antagonist	0
atropine	1
","	0
the	0
M1	0
-	0
selective	0
antagonists	0
pirenzepine	1
and	0
dicyclomine	1
and	0
the	0
acetylcholine	1
depletor	0
hemicholinium	1
-	2
3	2
","	0
but	0
not	0
by	0
the	0
opioid	0
antagonist	0
naloxone	1
","	0
the	0
gamma	1
-	2
aminobutyric	2
acidB	2
antagonist	0
3	1
-	2
aminopropyl	2
-	2
diethoxy	2
-	2
methyl	2
-	2
phosphinic	2
acid	2
","	0
the	0
H3	0
agonist	0
R	1
-	2
(	2
alpha	2
)	2
-	2
methylhistamine	2
","	0
the	0
D2	0
antagonist	0
quinpirole	1
","	0
the	0
5	1
-	2
hydroxytryptamine4	2
antagonist	0
2	1
-	2
methoxy	2
-	2
4	2
-	2
amino	2
-	2
5	2
-	2
chlorobenzoic	2
acid	2
2	2
-	2
(	2
diethylamino	2
)	2
ethyl	2
ester	2
hydrochloride	0
","	0
the	0
5	1
-	2
hydroxytryptamin1A	2
antagonist	0
1	1
-	2
(	2
2	2
-	2
methoxyphenyl	2
)	2
-	2
4	2
-	2
[	2
4	2
-	2
(	2
2	2
-	2
phthalimido	2
)	2
butyl	2
]	2
piperazine	2
hydrobromide	0
and	0
the	0
polyamines	0
depletor	0
reserpine	1
.	0
Based	0
on	0
these	0
data	0
","	0
it	0
can	0
be	0
postulated	0
that	0
(	0
+	0
/	0
-	0
)	0
-	0
PG	1
-	2
9	2
exerted	0
an	0
antinociceptive	0
effect	0
mediated	0
by	0
a	0
central	0
potentiation	0
of	0
cholinergic	0
transmission	0
.	0
(	0
+	0
/	0
-	0
)	0
-	0
PG	1
-	2
9	2
(	0
10	0
-	0
40	0
mg	0
kg	0
-	0
1	0
i	0
.	0
p	0
.	0
)	0
was	0
able	0
to	0
prevent	0
amnesia	3
induced	0
by	0
scopolamine	1
(	0
1	0
mg	0
kg	0
-	0
1	0
i	0
.	0
p	0
.	0
)	0
and	0
dicyclomine	1
(	0
2	0
mg	0
kg	0
-	0
1	0
i	0
.	0
p	0
.	0
)	0
in	0
the	0
mouse	0
passive	0
-	0
avoidance	0
test	0
.	0
Affinity	0
profiles	0
of	0
(	0
+	0
/	0
-	0
)	0
-	0
PG	1
-	2
9	2
for	0
muscarinic	0
receptor	0
subtypes	0
","	0
determined	0
by	0
functional	0
studies	0
(	0
rabbit	0
vas	0
deferens	0
for	0
M1	0
","	0
guinea	0
pig	0
atrium	0
for	0
M2	0
","	0
guinea	0
pig	0
ileum	0
for	0
M3	0
and	0
immature	0
guinea	0
pig	0
uterus	0
for	0
putative	0
M4	0
)	0
","	0
have	0
shown	0
an	0
M4	0
/	0
M1	0
selectivity	0
ratio	0
of	0
10	0
.	0
2	0
that	0
might	0
be	0
responsible	0
for	0
the	0
antinociception	0
and	0
the	0
anti	0
-	0
amnesic	3
effect	0
induced	0
by	0
(	0
+	0
/	0
-	0
)	0
-	0
PG	1
-	2
9	2
through	0
an	0
increase	0
in	0
acetylcholine	1
extracellular	0
levels	0
.	0
In	0
the	0
antinociceptive	0
and	0
antiamnesic	0
dose	0
range	0
","	0
(	0
+	0
/	0
-	0
)	0
-	0
PG	1
-	2
9	2
did	0
not	0
impair	0
mouse	0
performance	0
evaluated	0
by	0
the	0
rota	0
-	0
rod	0
test	0
and	0
Animex	0
apparatus	0
.	0
The	0
effect	0
of	0
different	0
anaesthetic	0
agents	0
in	0
hearing	3
loss	4
following	0
spinal	0
anaesthesia	0
.	0
The	0
cause	0
of	0
hearing	3
loss	4
after	0
spinal	0
anaesthesia	0
is	0
unknown	0
.	0
Up	0
until	0
now	0
","	0
the	0
only	0
factor	0
studied	0
has	0
been	0
the	0
effect	0
of	0
the	0
diameter	0
of	0
the	0
spinal	0
needle	0
on	0
post	0
-	0
operative	0
sensorineural	3
hearing	4
loss	4
.	0
The	0
aim	0
of	0
this	0
study	0
was	0
to	0
describe	0
this	0
hearing	3
loss	4
and	0
to	0
investigate	0
other	0
factors	0
influencing	0
the	0
degree	0
of	0
hearing	3
loss	4
.	0
Two	0
groups	0
of	0
22	0
similar	0
patients	0
were	0
studied	0
:	0
one	0
group	0
received	0
6	0
mL	0
prilocaine	1
2	0
%	0
;	0
and	0
the	0
other	0
received	0
3	0
mL	0
bupivacaine	1
0	0
.	0
5	0
%	0
.	0
Patients	0
given	0
prilocaine	1
were	0
more	0
likely	0
to	0
develop	0
hearing	3
loss	4
(	0
10	0
out	0
of	0
22	0
)	0
than	0
those	0
given	0
bupivacaine	1
(	0
4	0
out	0
of	0
22	0
)	0
(	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
The	0
average	0
hearing	3
loss	4
for	0
speech	0
frequencies	0
was	0
about	0
10	0
dB	0
after	0
prilocaine	1
and	0
15	0
dB	0
after	0
bupivacaine	1
.	0
None	0
of	0
the	0
patients	0
complained	0
of	0
subjective	0
hearing	3
loss	4
.	0
Long	0
-	0
term	0
follow	0
-	0
up	0
of	0
the	0
patients	0
was	0
not	0
possible	0
.	0
A	0
transient	0
neurological	3
deficit	4
following	0
intrathecal	0
injection	0
of	0
1	0
%	0
hyperbaric	0
bupivacaine	1
for	0
unilateral	0
spinal	0
anaesthesia	0
.	0
We	0
describe	0
a	0
case	0
of	0
transient	0
neurological	3
deficit	4
that	0
occurred	0
after	0
unilateral	0
spinal	0
anaesthesia	0
with	0
8	0
mg	0
of	0
1	0
%	0
hyperbaric	0
bupivacaine	1
slowly	0
injected	0
through	0
a	0
25	0
-	0
gauge	0
pencil	0
-	0
point	0
spinal	0
needle	0
.	0
The	0
surgery	0
and	0
anaesthesia	0
were	0
uneventful	0
","	0
but	0
3	0
days	0
after	0
surgery	0
","	0
the	0
patient	0
reported	0
an	0
area	0
of	0
hypoaesthesia	0
over	0
L3	0
-	0
L4	0
dermatomes	0
of	0
the	0
leg	0
which	0
had	0
been	0
operated	0
on	0
(	0
loss	3
of	4
pinprick	4
sensation	4
)	0
without	0
reduction	0
in	0
muscular	0
strength	0
.	0
Sensation	0
in	0
this	0
area	0
returned	0
to	0
normal	0
over	0
the	0
following	0
2	0
weeks	0
.	0
Prospective	0
multicentre	0
studies	0
with	0
a	0
large	0
population	0
and	0
a	0
long	0
follow	0
-	0
up	0
should	0
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in	0
order	0
to	0
evaluate	0
the	0
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of	0
this	0
unusual	0
side	0
effect	0
.	0
However	0
","	0
we	0
suggest	0
that	0
a	0
low	0
solution	0
concentration	0
should	0
be	0
preferred	0
for	0
unilateral	0
spinal	0
anaesthesia	0
with	0
a	0
hyperbaric	0
anaesthetic	0
solution	0
(	0
if	0
pencil	0
-	0
point	0
needle	0
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slow	0
injection	0
rate	0
are	0
employed	0
)	0
","	0
in	0
order	0
to	0
minimize	0
the	0
risk	0
of	0
a	0
localized	0
high	0
peak	0
anaesthetic	0
concentration	0
","	0
which	0
might	0
lead	0
to	0
a	0
transient	0
neurological	3
deficit	4
.	0
Transient	3
neurologic	4
symptoms	4
after	0
spinal	0
anesthesia	0
:	0
a	0
lower	0
incidence	0
with	0
prilocaine	1
and	0
bupivacaine	1
than	0
with	0
lidocaine	1
.	0
BACKGR0UND	0
:	0
Recent	0
evidence	0
suggests	0
that	0
transient	3
neurologic	4
symptoms	4
(	0
TNSs	3
)	0
frequently	0
follow	0
lidocaine	1
spinal	0
anesthesia	0
but	0
are	0
infrequent	0
with	0
bupivacaine	1
.	0
However	0
","	0
identification	0
of	0
a	0
short	0
-	0
acting	0
local	0
anesthetic	0
to	0
substitute	0
for	0
lidocaine	1
for	0
brief	0
surgical	0
procedures	0
remains	0
an	0
important	0
goal	0
.	0
Prilocaine	1
is	0
an	0
amide	0
local	0
anesthetic	0
with	0
a	0
duration	0
of	0
action	0
similar	0
to	0
that	0
of	0
lidocaine	1
.	0
Accordingly	0
","	0
the	0
present	0
","	0
prospective	0
double	0
-	0
blind	0
study	0
compares	0
prilocaine	1
with	0
lidocaine	1
and	0
bupivacaine	1
with	0
respect	0
to	0
duration	0
of	0
action	0
and	0
relative	0
risk	0
of	0
TNSs	3
.	0
METH0DS	0
:	0
Ninety	0
patients	0
classified	0
as	0
American	0
Society	0
of	0
Anesthesiologists	0
physical	0
status	0
I	0
or	0
II	0
who	0
were	0
scheduled	0
for	0
short	0
gynecologic	0
procedures	0
under	0
spinal	0
anesthesia	0
were	0
randomly	0
allocated	0
to	0
receive	0
2	0
.	0
5	0
ml	0
2	0
%	0
lidocaine	1
in	0
7	0
.	0
5	0
%	0
glucose	1
","	0
2	0
%	0
prilocaine	1
in	0
7	0
.	0
5	0
%	0
glucose	1
","	0
or	0
0	0
.	0
5	0
%	0
bupivacaine	1
in	0
7	0
.	0
5	0
%	0
glucose	1
.	0
All	0
solutions	0
were	0
provided	0
in	0
blinded	0
vials	0
by	0
the	0
hospital	0
pharmacy	0
.	0
Details	0
of	0
spinal	0
puncture	0
","	0
extension	0
and	0
regression	0
of	0
spinal	0
block	0
","	0
and	0
the	0
times	0
to	0
reach	0
discharge	0
criteria	0
were	0
noted	0
.	0
In	0
the	0
evening	0
of	0
postoperative	0
day	0
1	0
","	0
patients	0
were	0
evaluated	0
for	0
TNSs	3
by	0
a	0
physician	0
unaware	0
of	0
the	0
drug	0
administered	0
and	0
the	0
details	0
of	0
the	0
anesthetic	0
procedure	0
.	0
RESULTS	0
:	0
Nine	0
of	0
30	0
patients	0
receiving	0
lidocaine	1
experienced	0
TNSs	3
","	0
1	0
of	0
30	0
patients	0
receiving	0
prilocaine	1
(	0
P	0
=	0
0	0
.	0
3	0
)	0
had	0
them	0
","	0
and	0
none	0
of	0
30	0
patients	0
receiving	0
bupivacaine	1
had	0
TNSs	3
.	0
Times	0
to	0
ambulate	0
and	0
to	0
void	0
were	0
similar	0
after	0
lidocaine	1
and	0
prilocaine	1
(	0
150	0
vs	0
.	0
165	0
min	0
and	0
238	0
vs	0
.	0
253	0
min	0
","	0
respectively	0
)	0
but	0
prolonged	0
after	0
bupivacaine	1
(	0
200	0
and	0
299	0
min	0
","	0
respectively	0
;	0
P	0
<	0
0	0
.	0
5	0
)	0
.	0
C0NCLUSI0NS	0
:	0
Prilocaine	1
may	0
be	0
preferable	0
to	0
lidocaine	1
for	0
short	0
surgical	0
procedures	0
because	0
it	0
has	0
a	0
similar	0
duration	0
of	0
action	0
but	0
a	0
lower	0
incidence	0
of	0
TNSs	3
.	0
Suxamethonium	1
-	0
induced	0
cardiac	3
arrest	4
and	0
death	3
following	0
5	0
days	0
of	0
immobilization	0
.	0
The	0
present	0
report	0
describes	0
a	0
case	0
of	0
cardiac	3
arrest	4
and	0
subsequent	0
death	3
as	0
a	0
result	0
of	0
hyperkalaemia	3
following	0
the	0
use	0
of	0
suxamethonium	1
in	0
a	0
23	0
-	0
year	0
-	0
old	0
Malawian	0
woman	0
.	0
Five	0
days	0
after	0
the	0
onset	0
of	0
the	0
symptoms	0
of	0
meningitis	3
","	0
the	0
patient	0
aspirated	0
stomach	0
contents	0
and	0
needed	0
endotracheal	0
intubation	0
.	0
Forty	0
seconds	0
after	0
injection	0
of	0
suxamethonium	1
","	0
bradycardia	3
and	0
cardiac	3
arrest	4
occurred	0
.	0
Attempts	0
to	0
resuscitate	0
the	0
patient	0
were	0
not	0
successful	0
.	0
The	0
serum	0
level	0
of	0
potassium	1
was	0
observed	0
to	0
be	0
8	0
.	0
4	0
mequiv	0
L	0
-	0
1	0
.	0
Apart	0
from	0
the	0
reduction	0
in	0
the	0
patient	0
'	0
s	0
level	0
of	0
consciousness	0
","	0
there	0
were	0
no	0
signs	0
of	0
motor	0
neurone	0
damage	0
or	0
of	0
any	0
of	0
the	0
other	0
known	0
predisposing	0
conditions	0
for	0
hyperkalaemia	3
following	0
the	0
administration	0
of	0
suxamethonium	1
.	0
It	0
is	0
postulated	0
that	0
her	0
death	3
was	0
caused	0
by	0
hypersensitivity	3
to	0
suxamethonium	1
","	0
associated	0
with	0
her	0
5	0
-	0
day	0
immobilization	0
.	0
Acute	0
hepatitis	3
","	0
autoimmune	3
hemolytic	4
anemia	4
","	0
and	0
erythroblastocytopenia	3
induced	0
by	0
ceftriaxone	1
.	0
An	0
80	0
-	0
yr	0
-	0
old	0
man	0
developed	0
acute	0
hepatitis	3
shortly	0
after	0
ingesting	0
oral	0
ceftriaxone	1
.	0
Although	0
the	0
transaminases	0
gradually	0
returned	0
to	0
baseline	0
after	0
withholding	0
the	0
beta	1
lactam	2
antibiotic	0
","	0
there	0
was	0
a	0
gradual	0
increase	0
in	0
serum	0
bilirubin	1
and	0
a	0
decrease	0
in	0
hemoglobin	0
concentration	0
caused	0
by	0
an	0
autoimmune	3
hemolytic	4
anemia	4
and	0
erythroblastocytopenia	3
.	0
These	0
responded	0
to	0
systemic	0
steroids	1
and	0
immunoglobulins	0
.	0
Despite	0
the	0
widespread	0
use	0
of	0
these	0
agents	0
this	0
triad	0
of	0
side	0
effects	0
has	0
not	0
previously	0
been	0
reported	0
in	0
connection	0
with	0
beta	1
lactam	2
antibiotics	0
.	0
Thyroxine	1
abuse	0
:	0
an	0
unusual	0
case	0
of	0
thyrotoxicosis	3
in	0
pregnancy	0
.	0
Eating	3
disorders	4
and	0
the	0
associated	0
behavioural	0
problems	0
and	0
drug	3
abuse	4
are	0
uncommon	0
in	0
pregnancy	0
.	0
When	0
they	0
do	0
occur	0
they	0
are	0
often	0
unrecognized	0
because	0
of	0
denial	0
but	0
when	0
significant	0
may	0
pose	0
a	0
risk	0
to	0
both	0
the	0
mother	0
and	0
her	0
fetus	0
.	0
This	0
case	0
illustrates	0
a	0
number	0
of	0
problems	0
that	0
may	0
be	0
encountered	0
in	0
women	0
with	0
eating	3
disorders	4
in	0
pregnancy	0
","	0
including	0
prolonged	0
and	0
recurrent	0
metabolic	0
disturbances	0
and	0
diuretic	0
abuse	0
.	0
In	0
particular	0
it	0
illustrates	0
the	0
derangements	0
of	0
thyroid	0
function	0
seen	0
in	0
pregnant	0
women	0
with	0
eating	3
disorders	4
and	0
reminds	0
us	0
that	0
when	0
a	0
cause	0
for	0
thyrotoxicosis	3
remains	0
obscure	0
","	0
thyroxine	1
abuse	0
should	0
be	0
considered	0
and	0
explored	0
.	0
Repeated	0
trimipramine	1
induces	0
dopamine	1
D2	0
/	0
D3	0
and	0
alpha1	0
-	0
adrenergic	0
up	0
-	0
regulation	0
.	0
Trimipramine	1
(	0
TRI	1
)	0
","	0
which	0
shows	0
a	0
clinical	0
antidepressant	1
activity	0
","	0
is	0
chemically	0
related	0
to	0
imipramine	1
but	0
does	0
not	0
inhibit	0
the	0
reuptake	0
of	0
noradrenaline	1
and	0
5	1
-	2
hydroxytryptamine	2
","	0
nor	0
does	0
it	0
induce	0
beta	0
-	0
adrenergic	0
down	0
-	0
regulation	0
.	0
The	0
mechanism	0
of	0
its	0
antidepressant	1
activity	0
is	0
still	0
unknown	0
.	0
The	0
aim	0
of	0
the	0
present	0
study	0
was	0
to	0
find	0
out	0
whether	0
TRI	1
given	0
repeatedly	0
was	0
able	0
to	0
induce	0
adaptive	0
changes	0
in	0
the	0
dopaminergic	0
and	0
alpha1	0
-	0
adrenergic	0
systems	0
","	0
demonstrated	0
by	0
us	0
previously	0
for	0
various	0
antidepressants	1
.	0
TRI	1
was	0
given	0
to	0
male	0
Wistar	0
rats	0
and	0
male	0
Albino	0
Swiss	0
mice	0
perorally	0
twice	0
daily	0
for	0
14	0
days	0
.	0
In	0
the	0
acute	0
experiment	0
TRI	1
(	0
given	0
i	0
.	0
p	0
.	0
)	0
does	0
not	0
antagonize	0
the	0
reserpine	1
hypothermia	3
in	0
mice	0
and	0
does	0
not	0
potentiate	0
the	0
5	1
-	2
hydroxytryptophan	2
head	0
twitches	0
in	0
rats	0
.	0
TRI	1
given	0
repeatedly	0
to	0
rats	0
increases	0
the	0
locomotor	0
hyperactivity	3
induced	0
by	0
d	1
-	2
amphetamine	2
","	0
quinpirole	1
and	0
(	0
+	0
)	0
-	0
7	0
-	0
hydroxy	0
-	0
dipropyloaminotetralin	0
(	0
dopamine	1
D2	0
and	0
D3	0
effects	0
)	0
.	0
The	0
stereotypies	0
induced	0
by	0
d	1
-	2
amphetamine	2
or	0
apomorphine	1
are	0
not	0
potentiated	0
by	0
TRI	1
.	0
It	0
increases	0
the	0
behaviour	0
stimulation	0
evoked	0
by	0
phenylephrine	1
(	0
given	0
intraventricularly	0
)	0
in	0
rats	0
","	0
evaluated	0
in	0
the	0
open	0
field	0
test	0
as	0
well	0
as	0
the	0
aggressiveness	3
evoked	0
by	0
clonidine	1
in	0
mice	0
","	0
both	0
these	0
effects	0
being	0
mediated	0
by	0
an	0
alpha1	0
-	0
adrenergic	0
receptor	0
.	0
It	0
may	0
be	0
concluded	0
that	0
","	0
like	0
other	0
tricyclic	0
antidepressants	1
studied	0
previously	0
","	0
TRI	1
given	0
repeatedly	0
increases	0
the	0
responsiveness	0
of	0
brain	0
dopamine	1
D2	0
and	0
D3	0
(	0
locomotor	0
activity	0
but	0
not	0
stereotypy	0
)	0
as	0
well	0
as	0
alpha1	0
-	0
adrenergic	0
receptors	0
to	0
their	0
agonists	0
.	0
A	0
question	0
arises	0
whether	0
the	0
reuptake	0
inhibition	0
is	0
of	0
any	0
importance	0
to	0
the	0
adaptive	0
changes	0
induced	0
by	0
repeated	0
antidepressants	1
","	0
suggested	0
to	0
be	0
responsible	0
for	0
the	0
antidepressant	1
activity	0
.	0
Pethidine	1
-	0
associated	0
seizure	3
in	0
a	0
healthy	0
adolescent	0
receiving	0
pethidine	1
for	0
postoperative	3
pain	4
control	0
.	0
A	0
healthy	0
17	0
-	0
year	0
-	0
old	0
male	0
received	0
standard	0
intermittent	0
doses	0
of	0
pethidine	1
via	0
a	0
patient	0
-	0
controlled	0
analgesia	0
(	0
PCA	0
)	0
pump	0
for	0
management	0
of	0
postoperative	3
pain	4
control	0
.	0
Twenty	0
-	0
three	0
h	0
postoperatively	0
he	0
developed	0
a	0
brief	0
self	0
-	0
limited	0
seizure	3
.	0
Both	0
plasma	0
pethidine	1
and	0
norpethidine	1
were	0
elevated	0
in	0
the	0
range	0
associated	0
with	0
clinical	0
manifestations	0
of	0
central	0
nervous	0
system	0
excitation	0
.	0
No	0
other	0
risk	0
factors	0
for	0
CNS	0
toxicity	3
were	0
identified	0
.	0
This	0
method	0
allowed	0
frequent	0
self	0
-	0
dosing	0
of	0
pethidine	1
at	0
short	0
time	0
intervals	0
and	0
rapid	0
accumulation	0
of	0
pethidine	1
and	0
norpethidine	1
.	0
The	0
routine	0
use	0
of	0
pethidine	1
via	0
PCA	0
even	0
for	0
a	0
brief	0
postoperative	0
analgesia	0
should	0
be	0
reconsidered	0
.	0
An	0
unusual	0
toxic	0
reaction	0
to	0
axillary	0
block	0
by	0
mepivacaine	1
with	0
adrenaline	1
.	0
An	0
increase	3
in	4
blood	4
pressure	4
","	0
accompanied	0
by	0
atrial	3
fibrillation	4
","	0
agitation	3
","	0
incomprehensible	3
shouts	4
and	0
loss	3
of	4
consciousness	4
","	0
was	0
observed	0
in	0
an	0
elderly	0
","	0
ASA	0
classification	0
group	0
II	0
","	0
cardiovascularly	0
medicated	0
male	0
","	0
12	0
min	0
after	0
performance	0
of	0
axillary	0
block	0
with	0
mepivacaine	1
850	0
mg	0
containing	0
adrenaline	1
0	0
.	0
225	0
mg	0
","	0
for	0
correction	0
of	0
Dupuytren	3
'	4
s	4
contracture	4
.	0
After	0
intravenous	0
administration	0
of	0
labetalol	1
","	0
metoprolol	1
and	0
midazolam	1
the	0
patient	0
'	0
s	0
condition	0
improved	0
","	0
and	0
15	0
min	0
later	0
he	0
woke	0
up	0
.	0
The	0
block	0
was	0
successful	0
and	0
surgery	0
was	0
conducted	0
as	0
scheduled	0
despite	0
persisting	0
atrial	3
fibrillation	4
.	0
Postoperatively	0
","	0
the	0
patient	0
refused	0
DC	0
cardioversion	0
and	0
was	0
treated	0
medically	0
.	0
Both	0
the	0
temporal	0
relationship	0
of	0
events	0
and	0
the	0
response	0
to	0
treatment	0
suggest	0
that	0
a	0
rapid	0
systemic	0
absorption	0
of	0
mepivacaine	1
with	0
adrenaline	1
and	0
/	0
or	0
interaction	0
of	0
these	0
drugs	0
with	0
the	0
patient	0
'	0
s	0
cardiovascular	0
medications	0
were	0
responsible	0
for	0
the	0
perioperative	0
complications	0
.	0
Drug	0
-	0
associated	0
acute	0
-	0
onset	0
vanishing	3
bile	4
duct	4
and	0
Stevens	3
-	4
Johnson	4
syndromes	4
in	0
a	0
child	0
.	0
Acute	0
vanishing	3
bile	4
duct	4
syndrome	0
is	0
a	0
rare	0
but	0
established	0
cause	0
of	0
progressive	0
cholestasis	3
in	0
adults	0
","	0
is	0
most	0
often	0
drug	0
or	0
toxin	0
related	0
","	0
and	0
is	0
of	0
unknown	0
pathogenesis	0
.	0
It	0
has	0
not	0
been	0
reported	0
previously	0
in	0
children	0
.	0
Stevens	3
-	4
Johnson	4
syndrome	4
is	0
a	0
well	0
-	0
recognized	0
immune	0
complex	0
-	0
mediated	0
hypersensitivity	3
reaction	0
that	0
affects	0
all	0
age	0
groups	0
","	0
is	0
drug	0
or	0
infection	3
induced	0
","	0
and	0
has	0
classic	0
systemic	0
","	0
mucosal	0
","	0
and	0
dermatologic	0
manifestations	0
.	0
A	0
previously	0
healthy	0
child	0
who	0
developed	0
acute	0
","	0
severe	0
","	0
rapidly	0
progressive	0
vanishing	3
bile	4
duct	4
syndrome	4
shortly	0
after	0
Stevens	3
-	4
Johnson	4
syndrome	4
is	0
described	0
;	0
this	0
was	0
temporally	0
associated	0
with	0
ibuprofen	1
use	0
.	0
Despite	0
therapy	0
with	0
ursodeoxycholic	1
acid	2
","	0
prednisone	1
","	0
and	0
then	0
tacrolimus	1
","	0
her	0
cholestatic	3
disease	4
was	0
unrelenting	0
","	0
with	0
cirrhosis	3
shown	0
by	0
biopsy	0
6	0
months	0
after	0
presentation	0
.	0
This	0
case	0
documents	0
acute	0
drug	0
-	0
related	0
vanishing	3
bile	4
duct	4
syndrome	4
in	0
the	0
pediatric	0
age	0
group	0
and	0
suggests	0
shared	0
immune	0
mechanisms	0
in	0
the	0
pathogenesis	0
of	0
both	0
Stevens	3
-	4
Johnson	4
syndrome	4
and	0
vanishing	3
bile	4
duct	4
syndrome	4
.	0
High	0
incidence	0
of	0
primary	3
pulmonary	4
hypertension	4
associated	0
with	0
appetite	1
suppressants	2
in	0
Belgium	0
.	0
Primary	3
pulmonary	4
hypertension	4
is	0
a	0
rare	0
","	0
progressive	0
and	0
incurable	0
disease	0
","	0
which	0
has	0
been	0
associated	0
with	0
the	0
intake	0
of	0
appetite	1
suppressant	2
drugs	0
.	0
The	0
importance	0
of	0
this	0
association	0
was	0
evaluated	0
in	0
Belgium	0
while	0
this	0
country	0
still	0
had	0
no	0
restriction	0
on	0
the	0
prescription	0
of	0
appetite	1
suppressants	2
.	0
Thirty	0
-	0
five	0
patients	0
with	0
primary	3
pulmonary	4
hypertension	4
and	0
85	0
matched	0
controls	0
were	0
recruited	0
over	0
32	0
months	0
(	0
1992	0
-	0
1994	0
)	0
in	0
Belgium	0
.	0
Exposure	0
to	0
appetite	1
-	2
suppressants	2
was	0
assessed	0
on	0
the	0
basis	0
of	0
hospital	0
records	0
and	0
standardized	0
interview	0
.	0
Twenty	0
-	0
three	0
of	0
the	0
patients	0
had	0
previously	0
taken	0
appetite	1
suppressants	2
","	0
mainly	0
fenfluramines	1
","	0
as	0
compared	0
with	0
only	0
5	0
of	0
the	0
controls	0
(	0
66	0
versus	0
6	0
%	0
","	0
p	0
<	0
0	0
.	0
1	0
)	0
.	0
Five	0
patients	0
died	0
before	0
the	0
interview	0
","	0
all	0
of	0
them	0
had	0
taken	0
appetite	1
suppressants	2
.	0
In	0
8	0
patients	0
the	0
diagnosis	0
of	0
primary	3
pulmonary	4
hypertension	4
was	0
uncertain	0
","	0
5	0
of	0
them	0
had	0
taken	0
appetite	1
suppressants	2
.	0
The	0
patients	0
who	0
had	0
been	0
exposed	0
to	0
appetite	1
suppressants	2
tended	0
to	0
be	0
on	0
average	0
more	0
severely	0
ill	0
","	0
and	0
to	0
have	0
a	0
shorter	0
median	0
delay	0
between	0
onset	0
of	0
symptoms	0
and	0
diagnosis	0
.	0
A	0
policy	0
of	0
unrestricted	0
prescription	0
of	0
appetite	1
suppressants	2
may	0
lead	0
to	0
a	0
high	0
incidence	0
of	0
associated	0
primary	3
pulmonary	4
hypertension	4
.	0
Intake	0
of	0
appetite	1
suppressants	2
may	0
accelerate	0
the	0
progression	0
of	0
the	0
disease	0
.	0
Inappropriate	0
use	0
of	0
carbamazepine	1
and	0
vigabatrin	1
in	0
typical	0
absence	3
seizures	4
.	0
Carbamazepine	1
and	0
vigabatrin	1
are	0
contraindicated	0
in	0
typical	0
absence	3
seizures	4
.	0
0f	0
18	0
consecutive	0
referrals	0
of	0
children	0
with	0
resistant	0
typical	0
absences	0
only	0
","	0
eight	0
were	0
erroneously	0
treated	0
with	0
carbamazepine	1
either	0
as	0
monotherapy	0
or	0
as	0
an	0
add	0
-	0
on	0
.	0
Vigabatrin	1
was	0
also	0
used	0
in	0
the	0
treatment	0
of	0
two	0
children	0
.	0
Frequency	0
of	0
absences	0
increased	0
in	0
four	0
children	0
treated	0
with	0
carbamazepine	1
and	0
two	0
of	0
these	0
developed	0
myoclonic	3
jerks	4
","	0
which	0
resolved	0
on	0
withdrawal	0
of	0
carbamazepine	1
.	0
Absences	0
were	0
aggravated	0
in	0
both	0
cases	0
where	0
vigabatrin	1
was	0
added	0
on	0
to	0
concurrent	0
treatment	0
.	0
0ptimal	0
control	0
of	0
the	0
absences	0
was	0
achieved	0
with	0
sodium	1
valproate	2
","	0
lamotrigine	1
","	0
or	0
ethosuximide	1
alone	0
or	0
in	0
combination	0
.	0
Choreoathetoid	3
movements	4
associated	0
with	0
rapid	0
adjustment	0
to	0
methadone	1
.	0
Choreatiform	3
hyperkinesias	4
are	0
known	0
to	0
be	0
occasional	0
movement	3
abnormalities	4
during	0
intoxications	0
with	0
cocaine	1
but	0
not	0
opiates	0
.	0
This	0
is	0
a	0
case	0
report	0
of	0
euphoria	0
and	0
choreoathetoid	3
movements	4
both	0
transiently	0
induced	0
by	0
rapid	0
adjustment	0
to	0
the	0
selective	0
mu	0
-	0
opioid	0
receptor	0
agonist	0
methadone	1
in	0
an	0
inpatient	0
previously	0
abusing	0
heroine	1
and	0
cocaine	1
.	0
In	0
addition	0
","	0
minor	0
EEG	0
abnormalities	0
occurred	0
.	0
Possible	0
underlying	0
neurobiological	0
phenomena	0
are	0
discussed	0
.	0
Adverse	0
effects	0
of	0
the	0
atypical	0
antipsychotics	0
.	0
Collaborative	0
Working	0
Group	0
on	0
Clinical	0
Trial	0
Evaluations	0
.	0
Adverse	0
effects	0
of	0
antipsychotics	0
often	0
lead	0
to	0
noncompliance	0
.	0
Thus	0
","	0
clinicians	0
should	0
address	0
patients	0
'	0
concerns	0
about	0
adverse	0
effects	0
and	0
attempt	0
to	0
choose	0
medications	0
that	0
will	0
improve	0
their	0
patients	0
'	0
quality	0
of	0
life	0
as	0
well	0
as	0
overall	0
health	0
.	0
The	0
side	0
effect	0
profiles	0
of	0
the	0
atypical	0
antipsychotics	0
are	0
more	0
advantageous	0
than	0
those	0
of	0
the	0
conventional	0
neuroleptics	0
.	0
Conventional	0
agents	0
are	0
associated	0
with	0
unwanted	0
central	0
nervous	0
system	0
effects	0
","	0
including	0
extrapyramidal	3
symptoms	4
(	0
EPS	3
)	0
","	0
tardive	3
dyskinesia	4
","	0
sedation	0
","	0
and	0
possible	0
impairment	0
of	0
some	0
cognitive	0
measures	0
","	0
as	0
well	0
as	0
cardiac	0
effects	0
","	0
orthostatic	3
hypotension	4
","	0
hepatic	0
changes	0
","	0
anticholinergic	0
side	0
effects	0
","	0
sexual	3
dysfunction	4
","	0
and	0
weight	3
gain	4
.	0
The	0
newer	0
atypical	0
agents	0
have	0
a	0
lower	0
risk	0
of	0
EPS	3
","	0
but	0
are	0
associated	0
in	0
varying	0
degrees	0
with	0
sedation	0
","	0
cardiovascular	0
effects	0
","	0
anticholinergic	0
effects	0
","	0
weight	3
gain	4
","	0
sexual	3
dysfunction	4
","	0
hepatic	0
effects	0
","	0
lowered	0
seizure	3
threshold	0
(	0
primarily	0
clozapine	1
)	0
","	0
and	0
agranulocytosis	3
(	0
clozapine	1
only	0
)	0
.	0
Since	0
the	0
incidence	0
and	0
severity	0
of	0
specific	0
adverse	0
effects	0
differ	0
among	0
the	0
various	0
atypicals	0
","	0
the	0
clinician	0
should	0
carefully	0
consider	0
which	0
side	0
effects	0
are	0
most	0
likely	0
to	0
lead	0
to	0
the	0
individual	0
'	0
s	0
dissatisfaction	0
and	0
noncompliance	0
before	0
choosing	0
an	0
antipsychotic	0
for	0
a	0
particular	0
patient	0
.	0
A	0
randomized	0
","	0
placebo	0
-	0
controlled	0
dose	0
-	0
comparison	0
trial	0
of	0
haloperidol	1
for	0
psychosis	3
and	0
disruptive	3
behaviors	4
in	0
Alzheimer	3
'	4
s	4
disease	4
.	0
0BJECTIVE	0
:	0
The	0
goal	0
of	0
this	0
study	0
was	0
to	0
compare	0
the	0
efficacy	0
and	0
side	0
effects	0
of	0
two	0
doses	0
of	0
haloperidol	1
and	0
placebo	0
in	0
the	0
treatment	0
of	0
psychosis	3
and	0
disruptive	3
behaviors	4
in	0
patients	0
with	0
Alzheimer	3
'	4
s	4
disease	4
.	0
METH0D	0
:	0
In	0
a	0
6	0
-	0
week	0
random	0
-	0
assignment	0
","	0
double	0
-	0
blind	0
","	0
placebo	0
-	0
controlled	0
trial	0
(	0
phase	0
A	0
)	0
","	0
haloperidol	1
","	0
2	0
-	0
3	0
mg	0
/	0
day	0
(	0
standard	0
dose	0
)	0
","	0
and	0
haloperidol	1
","	0
0	0
.	0
50	0
-	0
0	0
.	0
75	0
mg	0
/	0
day	0
(	0
low	0
dose	0
)	0
","	0
were	0
compared	0
in	0
71	0
outpatients	0
with	0
Alzheimer	3
'	4
s	4
disease	4
.	0
For	0
the	0
subsequent	0
6	0
-	0
week	0
double	0
-	0
blind	0
crossover	0
phase	0
(	0
phase	0
B	0
)	0
","	0
patients	0
taking	0
standard	0
-	0
or	0
low	0
-	0
dose	0
haloperidol	1
were	0
switched	0
to	0
placebo	0
","	0
and	0
patients	0
taking	0
placebo	0
were	0
randomly	0
assigned	0
to	0
standard	0
-	0
or	0
low	0
-	0
dose	0
haloperidol	1
.	0
RESULTS	0
:	0
For	0
the	0
60	0
patients	0
who	0
completed	0
phase	0
A	0
","	0
standard	0
-	0
dose	0
haloperidol	1
was	0
efficacious	0
and	0
superior	0
to	0
both	0
low	0
-	0
dose	0
haloperidol	1
and	0
placebo	0
for	0
scores	0
on	0
the	0
Brief	0
Psychiatric	0
Rating	0
Scale	0
psychosis	3
factor	0
and	0
on	0
psychomotor	3
agitation	4
.	0
Response	0
rates	0
according	0
to	0
three	0
sets	0
of	0
criteria	0
were	0
greater	0
with	0
the	0
standard	0
dose	0
(	0
55	0
%	0
-	0
60	0
%	0
)	0
than	0
the	0
low	0
dose	0
(	0
25	0
%	0
-	0
35	0
%	0
)	0
and	0
placebo	0
(	0
25	0
%	0
-	0
30	0
%	0
)	0
.	0
The	0
advantage	0
of	0
standard	0
dose	0
over	0
low	0
dose	0
was	0
replicated	0
in	0
phase	0
B	0
.	0
In	0
phase	0
A	0
","	0
extrapyramidal	3
signs	4
tended	0
to	0
be	0
greater	0
with	0
the	0
standard	0
dose	0
than	0
in	0
the	0
other	0
two	0
conditions	0
","	0
primarily	0
because	0
of	0
a	0
subgroup	0
(	0
20	0
%	0
)	0
who	0
developed	0
moderate	0
to	0
severe	0
signs	0
.	0
Low	0
-	0
dose	0
haloperidol	1
did	0
not	0
differ	0
from	0
placebo	0
on	0
any	0
measure	0
of	0
efficacy	0
or	0
side	0
effects	0
.	0
C0NCLUSI0NS	0
:	0
The	0
results	0
indicated	0
a	0
favorable	0
therapeutic	0
profile	0
for	0
haloperidol	1
in	0
doses	0
of	0
2	0
-	0
3	0
mg	0
/	0
day	0
","	0
although	0
a	0
subgroup	0
developed	0
moderate	0
to	0
severe	0
extrapyramidal	3
signs	4
.	0
A	0
starting	0
dose	0
of	0
1	0
mg	0
/	0
day	0
with	0
gradual	0
","	0
upward	0
dose	0
titration	0
is	0
recommended	0
.	0
The	0
narrow	0
therapeutic	0
window	0
observed	0
with	0
haloperidol	1
may	0
also	0
apply	0
to	0
other	0
neuroleptics	0
used	0
in	0
Alzheimer	3
'	4
s	4
disease	4
patients	0
with	0
psychosis	3
and	0
disruptive	3
behaviors	4
.	0
Effects	0
of	0
acetylsalicylic	1
acid	2
","	0
dipyridamole	1
","	0
and	0
hydrocortisone	1
on	0
epinephrine	1
-	0
induced	0
myocardial	3
injury	4
in	0
dogs	0
.	0
A	0
reproducible	0
model	0
for	0
producing	0
diffuse	0
myocardial	3
injury	4
(	0
epinephrine	1
infusion	0
)	0
has	0
been	0
developed	0
to	0
study	0
the	0
cardioprotective	0
effects	0
of	0
agents	0
or	0
maneuvers	0
which	0
might	0
alter	0
the	0
evolution	0
of	0
acute	0
myocardial	3
infarction	4
.	0
Infusions	0
of	0
epinephrine	1
(	0
4	0
mug	0
per	0
kilogram	0
per	0
minute	0
for	0
6	0
hours	0
)	0
increased	0
radiocalcium	1
uptakes	0
into	0
intact	0
myocardium	0
and	0
each	0
of	0
its	0
subcellular	0
components	0
with	0
the	0
mitochondrial	0
fraction	0
showing	0
the	0
most	0
consistent	0
changes	0
when	0
compared	0
to	0
saline	0
-	0
infused	0
control	0
animals	0
(	0
4	0
","	0
957	0
vs	0
.	0
827	0
counts	0
per	0
minute	0
per	0
gram	0
of	0
dried	0
tissue	0
or	0
fraction	0
)	0
.	0
Myocardial	0
concentrations	0
of	0
calcium	1
also	0
increased	0
significantly	0
(	0
12	0
.	0
0	0
vs	0
.	0
5	0
.	0
0	0
mg	0
.	0
per	0
100	0
Gm	0
.	0
of	0
fat	0
-	0
free	0
dry	0
weight	0
)	0
.	0
Infusions	0
of	0
calcium	1
chloride	2
sufficient	0
to	0
raise	0
serum	0
calcium	1
concentrations	0
2	0
mEq	0
.	0
per	0
liter	0
failed	0
to	0
increase	0
calcium	1
influx	0
into	0
the	0
myocardial	0
cell	0
.	0
Mitochondrial	0
radiocalcium	1
uptakes	0
were	0
significantly	0
decreased	0
in	0
animals	0
pretreated	0
with	0
acetylsalicylic	1
acid	2
or	0
dipyridamole	1
or	0
when	0
hydrocortisone	1
was	0
added	0
to	0
the	0
epinephrine	1
infusion	0
(	0
2	0
","	0
682	0
","	0
2	0
","	0
803	0
","	0
and	0
3	0
","	0
424	0
counts	0
per	0
minute	0
per	0
gram	0
of	0
dried	0
fraction	0
","	0
respectively	0
)	0
.	0
Myocardial	0
calcium	1
concentrations	0
also	0
were	0
decreased	0
(	0
11	0
.	0
2	0
","	0
8	0
.	0
3	0
","	0
and	0
8	0
.	0
9	0
mg	0
.	0
per	0
100	0
Gm	0
.	0
of	0
fat	0
-	0
free	0
dry	0
weight	0
","	0
respectively	0
)	0
in	0
the	0
three	0
treatment	0
groups	0
","	0
being	0
significantly	0
decreased	0
only	0
in	0
the	0
last	0
two	0
.	0
Evidence	0
of	0
microscopic	0
damage	0
was	0
graded	0
as	0
less	0
severe	0
in	0
the	0
three	0
treatment	0
groups	0
.	0
Acetylsalicylic	1
acid	2
","	0
dipyridamole	1
","	0
and	0
hydrocortisone	1
all	0
appear	0
to	0
have	0
cardioprotective	0
effects	0
when	0
tested	0
in	0
this	0
model	0
.	0
Clinical	0
and	0
histopathologic	0
examination	0
of	0
renal	0
allografts	0
treated	0
with	0
tacrolimus	1
(	0
FK506	1
)	0
for	0
at	0
least	0
one	0
year	0
.	0
BACKGR0UND	0
:	0
We	0
clinically	0
and	0
pathologically	0
analyzed	0
renal	0
allografts	0
from	0
1	0
9	0
renal	0
transplant	0
patients	0
treated	0
with	0
tacrolimus	1
(	0
FK506	1
)	0
for	0
more	0
than	0
1	0
year	0
.	0
METH0DS	0
:	0
Twenty	0
-	0
six	0
renal	0
allograft	0
biopsy	0
specimens	0
from	0
1	0
9	0
renal	0
transplant	0
patients	0
who	0
underwent	0
transplantations	0
between	0
1991	0
and	0
1993	0
were	0
evaluated	0
.	0
Thirteen	0
biopsies	0
were	0
performed	0
from	0
stable	0
functioning	0
renal	0
allografts	0
with	0
informed	0
consent	0
(	0
nonepisode	0
biopsy	0
)	0
and	0
the	0
other	0
13	0
were	0
from	0
dysfunctional	0
renal	0
allografts	0
with	0
a	0
clinical	0
indication	0
for	0
biopsy	0
(	0
episode	0
biopsy	0
)	0
.	0
RESULTS	0
:	0
The	0
main	0
pathologic	0
diagnoses	0
(	0
some	0
overlap	0
)	0
were	0
acute	0
rejection	0
(	0
AR	0
;	0
n	0
=	0
4	0
)	0
","	0
chronic	0
rejection	0
(	0
CR	0
;	0
n	0
=	0
5	0
)	0
","	0
AR	0
+	0
CR	0
(	0
n	0
=	0
4	0
)	0
","	0
recurrent	0
IgA	3
nephropathy	4
(	0
n	0
=	0
5	0
)	0
","	0
normal	0
findings	0
(	0
n	0
=	0
2	0
)	0
","	0
minimal	0
-	0
type	0
chronic	0
FK506	1
nephropathy	3
(	0
n	0
=	0
9	0
)	0
","	0
and	0
mild	0
-	0
type	0
FK506	1
nephropathy	3
(	0
n	0
=	0
11	0
)	0
.	0
0f	0
the	0
nonepisode	0
biopsies	0
","	0
7	0
and	0
4	0
biopsies	0
showed	0
minimal	0
-	0
type	0
and	0
mild	0
-	0
type	0
chronic	0
FK506	1
nephropathy	3
","	0
respectively	0
.	0
Chronic	0
FK506	1
nephropathy	3
consisted	0
of	0
rough	0
and	0
foamy	0
tubular	0
vacuolization	0
(	0
5	0
biopsies	0
)	0
","	0
arteriolopathy	0
(	0
angiodegeneration	0
of	0
the	0
arteriolar	0
wall	0
;	0
20	0
biopsies	0
)	0
","	0
focal	3
segmental	4
glomerulosclerosis	4
(	0
4	0
biopsies	0
)	0
and	0
the	0
striped	0
form	0
of	0
interstitial	3
fibrosis	4
(	0
11	0
biopsies	0
)	0
.	0
The	0
serum	0
creatinine	1
levels	0
of	0
patients	0
in	0
the	0
mild	0
-	0
type	0
chronic	0
FK506	1
nephropathy	3
group	0
","	0
which	0
included	0
7	0
episode	0
biopsies	0
","	0
were	0
statistically	0
higher	0
than	0
those	0
in	0
the	0
minimum	0
-	0
type	0
chronic	0
FK506	1
-	0
nephropathy	3
group	0
(	0
P	0
<	0
0	0
.	0
1	0
)	0
.	0
C0NCLUSI0NS	0
:	0
This	0
study	0
demonstrates	0
that	0
chronic	0
FK506	1
nephropathy	3
consists	0
primarily	0
of	0
arteriolopathy	0
manifesting	0
as	0
insudative	0
hyalinosis	0
of	0
the	0
arteriolar	0
wall	0
","	0
and	0
suggests	0
that	0
mild	0
-	0
type	0
chronic	0
FK506	1
nephropathy	3
is	0
a	0
condition	0
which	0
may	0
lead	0
to	0
deterioration	0
of	0
renal	0
allograft	0
function	0
.	0
Different	0
lobular	0
distributions	0
of	0
altered	0
hepatocyte	0
tight	0
junctions	0
in	0
rat	0
models	0
of	0
intrahepatic	3
and	4
extrahepatic	4
cholestasis	4
.	0
Hepatocyte	0
tight	0
junctions	0
(	0
TJs	0
)	0
","	0
the	0
only	0
intercellular	0
barrier	0
between	0
the	0
sinusoidal	0
and	0
the	0
canalicular	0
spaces	0
","	0
play	0
a	0
key	0
role	0
in	0
bile	0
formation	0
.	0
Although	0
hepatocyte	0
TJs	0
are	0
impaired	0
in	0
cholestasis	3
","	0
attempts	0
to	0
localize	0
the	0
precise	0
site	0
of	0
hepatocyte	0
TJ	0
damage	0
by	0
freeze	0
-	0
fracture	0
electron	0
microscopy	0
have	0
produced	0
limited	0
information	0
.	0
Recently	0
","	0
several	0
TJ	0
-	0
associated	0
proteins	0
like	0
Z0	0
-	0
1	0
and	0
7H6	0
have	0
been	0
identified	0
and	0
characterized	0
.	0
Immunolocalization	0
of	0
7H6	0
appears	0
to	0
closely	0
correlate	0
with	0
paracellular	0
permeability	0
.	0
We	0
used	0
rat	0
models	0
of	0
intrahepatic	3
cholestasis	4
by	0
ethinyl	1
estradiol	2
(	0
EE	1
)	0
treatment	0
and	0
extrahepatic	3
cholestasis	4
by	0
bile	0
duct	0
ligation	0
(	0
BDL	0
)	0
to	0
precisely	0
determine	0
the	0
site	0
of	0
TJ	0
damage	0
.	0
Alterations	0
in	0
hepatocyte	0
TJs	0
were	0
assessed	0
by	0
double	0
-	0
immunolabeling	0
for	0
7H6	0
and	0
Z0	0
-	0
1	0
using	0
a	0
confocal	0
laser	0
scanning	0
microscope	0
.	0
In	0
control	0
rats	0
","	0
immunostaining	0
for	0
7H6	0
and	0
Z0	0
-	0
1	0
colocalized	0
to	0
outline	0
bile	0
canaliculi	0
in	0
a	0
continuous	0
fashion	0
.	0
In	0
contrast	0
","	0
7H6	0
and	0
Z0	0
-	0
1	0
immunostaining	0
was	0
more	0
discontinuous	0
","	0
outlining	0
the	0
bile	0
canaliculi	0
after	0
BDL	0
.	0
Immunostaining	0
for	0
7H6	0
","	0
not	0
Z0	0
-	0
1	0
","	0
decreased	0
and	0
predominantly	0
appeared	0
as	0
discrete	0
signals	0
in	0
the	0
submembranous	0
cytoplasm	0
of	0
periportal	0
hepatocytes	0
after	0
BDL	0
.	0
After	0
EE	1
treatment	0
","	0
changes	0
in	0
immunostaining	0
for	0
7H6	0
and	0
Z0	0
-	0
1	0
were	0
similar	0
to	0
those	0
seen	0
in	0
periportal	0
hepatocytes	0
after	0
BDL	0
","	0
but	0
distributed	0
more	0
diffusely	0
throughout	0
the	0
lobule	0
.	0
This	0
study	0
is	0
the	0
first	0
to	0
demonstrate	0
that	0
impairment	0
of	0
hepatocyte	0
TJs	0
occurs	0
heterogenously	0
in	0
the	0
liver	0
lobule	0
after	0
BDL	0
and	0
suggests	0
that	0
BDL	0
and	0
EE	1
treatments	0
produce	0
different	0
lobular	0
distributions	0
of	0
increased	0
paracellular	0
permeability	0
.	0
Memory	0
facilitation	0
and	0
stimulation	0
of	0
endogenous	0
nerve	0
growth	0
factor	0
synthesis	0
by	0
the	0
acetylcholine	1
releaser	0
PG	1
-	2
9	2
.	0
The	0
effects	0
of	0
PG	1
-	2
9	2
(	0
3alpha	1
-	2
tropyl	2
2	2
-	2
(	2
p	2
-	2
bromophenyl	2
)	2
propionate	2
)	0
","	0
the	0
acetylcholine	1
releaser	0
","	0
on	0
memory	0
processes	0
and	0
nerve	0
growth	0
factor	0
(	0
NGF	0
)	0
synthesis	0
were	0
evaluated	0
.	0
In	0
the	0
mouse	0
passive	0
-	0
avoidance	0
test	0
","	0
PG	1
-	2
9	2
(	0
10	0
-	0
30	0
mg	0
/	0
kg	0
","	0
i	0
.	0
p	0
.	0
)	0
","	0
administered	0
20	0
min	0
before	0
the	0
training	0
session	0
","	0
prevented	0
amnesia	3
induced	0
by	0
both	0
the	0
non	0
selective	0
antimuscarinic	0
drug	0
scopolamine	1
and	0
the	0
M1	0
-	0
selective	0
antagonist	0
S	1
-	2
(	2
-	2
)	2
-	2
ET	2
-	2
126	2
.	0
In	0
the	0
same	0
experimental	0
conditions	0
","	0
PG	1
-	2
9	2
(	0
5	0
-	0
20	0
microg	0
per	0
mouse	0
","	0
i	0
.	0
c	0
.	0
v	0
.	0
)	0
was	0
also	0
able	0
to	0
prevent	0
antimuscarine	0
-	0
induced	0
amnesia	3
","	0
demonstrating	0
a	0
central	0
localization	0
of	0
the	0
activity	0
.	0
At	0
the	0
highest	0
effective	0
doses	0
","	0
PG	1
-	2
9	2
did	0
not	0
produce	0
any	0
collateral	0
symptoms	0
as	0
revealed	0
by	0
the	0
Irwin	0
test	0
","	0
and	0
it	0
did	0
not	0
modify	0
spontaneous	0
motility	0
and	0
inspection	0
activity	0
","	0
as	0
revealed	0
by	0
the	0
hole	0
-	0
board	0
test	0
.	0
PG	1
-	2
9	2
was	0
also	0
able	0
to	0
increase	0
the	0
amount	0
of	0
NGF	0
secreted	0
in	0
vitro	0
by	0
astrocytes	0
in	0
a	0
dose	0
-	0
dependent	0
manner	0
.	0
The	0
maximal	0
NGF	0
contents	0
obtained	0
by	0
PG	1
-	2
9	2
were	0
17	0
.	0
6	0
-	0
fold	0
of	0
the	0
control	0
value	0
.	0
During	0
culture	0
","	0
no	0
morphological	0
changes	0
were	0
found	0
at	0
effective	0
concentrations	0
of	0
PG	1
-	2
9	2
.	0
The	0
current	0
work	0
indicates	0
the	0
ability	0
of	0
PG	1
-	2
9	2
to	0
induce	0
beneficial	0
effects	0
on	0
cognitive	0
processes	0
and	0
stimulate	0
activity	0
of	0
NGF	0
synthesis	0
in	0
astroglial	0
cells	0
.	0
Therefore	0
","	0
PG	1
-	2
9	2
could	0
represent	0
a	0
potential	0
useful	0
drug	0
able	0
to	0
improve	0
the	0
function	0
of	0
impaired	0
cognitive	0
processes	0
.	0
Mechanisms	0
of	0
FK	1
506	2
-	0
induced	0
hypertension	3
in	0
the	0
rat	0
.	0
-	0
Tacrolimus	1
(	0
FK	1
506	2
)	0
is	0
a	0
powerful	0
","	0
widely	0
used	0
immunosuppressant	0
.	0
The	0
clinical	0
utility	0
of	0
FK	1
506	2
is	0
complicated	0
by	0
substantial	0
hypertension	3
and	0
nephrotoxicity	3
.	0
To	0
clarify	0
the	0
mechanisms	0
of	0
FK	1
506	2
-	0
induced	0
hypertension	3
","	0
we	0
studied	0
the	0
chronic	0
effects	0
of	0
FK	1
506	2
on	0
the	0
synthesis	0
of	0
endothelin	0
-	0
1	0
(	0
ET	0
-	0
1	0
)	0
","	0
the	0
expression	0
of	0
mRNA	0
of	0
ET	0
-	0
1	0
and	0
endothelin	0
-	0
converting	0
enzyme	0
-	0
1	0
(	0
ECE	0
-	0
1	0
)	0
","	0
the	0
endothelial	0
nitric	1
oxide	2
synthase	0
(	0
eN0S	0
)	0
activity	0
","	0
and	0
the	0
expression	0
of	0
mRNA	0
of	0
eN0S	0
and	0
C	0
-	0
type	0
natriuretic	0
peptide	0
(	0
CNP	0
)	0
in	0
rat	0
blood	0
vessels	0
.	0
In	0
addition	0
","	0
the	0
effect	0
of	0
the	0
specific	0
endothelin	0
type	0
A	0
receptor	0
antagonist	0
FR	1
139317	2
on	0
FK	1
506	2
-	0
induced	0
hypertension	3
in	0
rats	0
was	0
studied	0
.	0
FK	1
506	2
","	0
5	0
mg	0
.	0
kg	0
-	0
1	0
.	0
d	0
-	0
1	0
given	0
for	0
4	0
weeks	0
","	0
elevated	0
blood	0
pressure	0
from	0
102	0
+	0
/	0
-	0
13	0
to	0
152	0
+	0
/	0
-	0
15	0
mm	0
Hg	0
and	0
increased	0
the	0
synthesis	0
of	0
ET	0
-	0
1	0
and	0
the	0
levels	0
of	0
ET	0
-	0
1	0
mRNA	0
in	0
the	0
mesenteric	0
artery	0
(	0
240	0
%	0
and	0
230	0
%	0
","	0
respectively	0
)	0
.	0
Little	0
change	0
was	0
observed	0
in	0
the	0
expression	0
of	0
ECE	0
-	0
1	0
mRNA	0
and	0
CNP	0
mRNA	0
.	0
FK	1
506	2
decreased	0
eN0S	0
activity	0
and	0
the	0
levels	0
of	0
eN0S	0
mRNA	0
in	0
the	0
aorta	0
(	0
48	0
%	0
and	0
55	0
%	0
","	0
respectively	0
)	0
.	0
The	0
administration	0
of	0
FR	1
139317	2
(	0
10	0
mg	0
.	0
kg	0
-	0
1	0
.	0
d	0
-	0
1	0
)	0
prevented	0
FK	1
506	2
-	0
induced	0
hypertension	3
in	0
rats	0
.	0
These	0
results	0
indicate	0
that	0
FK	1
506	2
may	0
increase	0
blood	0
pressure	0
not	0
only	0
by	0
increasing	0
ET	0
-	0
1	0
production	0
but	0
also	0
by	0
decreasing	0
N0	1
synthesis	0
in	0
the	0
vasculature	0
.	0