Torsade O
de O
pointes O
ventricular O
tachycardia O
during O
low O
dose O
intermittent O
dobutamine B
treatment O
in O
a O
patient O
with O
dilated O
cardiomyopathy O
and O
congestive O
heart O
failure O
. O

The O
authors O
describe O
the O
case O
of O
a O
56 O
- O
year O
- O
old O
woman O
with O
chronic O
, O
severe O
heart O
failure O
secondary O
to O
dilated O
cardiomyopathy O
and O
absence O
of O
significant O
ventricular O
arrhythmias O
who O
developed O
QT O
prolongation O
and O
torsade O
de O
pointes O
ventricular O
tachycardia O
during O
one O
cycle O
of O
intermittent O
low O
dose O
( O
2 O
. O
5 O
mcg O
/ O
kg O
per O
min O
) O
dobutamine B
. O

This O
report O
of O
torsade O
de O
pointes O
ventricular O
tachycardia O
during O
intermittent O
dobutamine B
supports O
the O
hypothesis O
that O
unpredictable O
fatal O
arrhythmias O
may O
occur O
even O
with O
low O
doses O
and O
in O
patients O
with O
no O
history O
of O
significant O
rhythm O
disturbances O
. O

The O
mechanisms O
of O
proarrhythmic O
effects O
of O
Dubutamine B
are O
discussed O
. O

Positive O
skin O
tests O
in O
late O
reactions O
to O
radiographic O
contrast B
media I
. O

In O
the O
last O
few O
years O
delayed O
reactions O
several O
hours O
after O
the O
injection O
of O
radiographic O
and O
contrast O
materials O
( O
PRC O
) O
have O
been O
described O
with O
increasing O
frequency O
. O

The O
authors O
report O
two O
observations O
on O
patients O
with O
delayed O
reactions O
in O
whom O
intradermoreactions O
( O
IDR O
) O
and O
patch O
tests O
to O
a O
series O
of O
ionic O
and O
non O
ionic O
PRC O
were O
studied O
. O

After O
angiography O
by O
the O
venous O
route O
in O
patient O
n O
degree O
1 O
a O
biphasic O
reaction O
with O
an O
immediate O
reaction O
( O
dyspnea O
, O
loss O
of O
consciousness O
) O
and O
delayed O
macro O
- O
papular O
rash O
appeared O
, O
whilst O
patient O
n O
degree O
2 O
developed O
a O
generalised O
sensation O
of O
heat O
, O
persistent O
pain O
at O
the O
site O
of O
injection O
immediately O
and O
a O
generalised O
macro O
- O
papular O
reaction O
after O
24 O
hours O
. O

The O
skin O
tests O
revealed O
positive O
delayed O
reactions O
of O
24 O
hours O
and O
48 O
hours O
by O
IDR O
and O
patch O
tests O
to O
only O
some O
PRC O
with O
common O
chains O
in O
their O
structures O
. O

The O
positive O
skin O
tests O
are O
in O
favour O
of O
immunological O
reactions O
and O
may O
help O
in O
diagnosis O
of O
allergy O
in O
the O
patients O
. O

Risk O
of O
transient O
hyperammonemic O
encephalopathy O
in O
cancer O
patients O
who O
received O
continuous O
infusion O
of O
5 B
- I
fluorouracil I
with O
the O
complication O
of O
dehydration O
and O
infection O
. O

From O
1986 O
to O
1998 O
, O
29 O
cancer O
patients O
who O
had O
32 O
episodes O
of O
transient O
hyperammonemic O
encephalopathy O
related O
to O
continuous O
infusion O
of O
5 B
- I
fluorouracil I
( O
5 B
- I
FU I
) O
were O
identified O
. O

None O
of O
the O
patients O
had O
decompensated O
liver O
disease O
. O

Onset O
of O
hyperammonemic O
encephalopathy O
varied O
from O
0 O
. O
5 O
to O
5 O
days O
( O
mean O
: O
2 O
. O
6 O
+ O
/ O
- O
1 O
. O
3 O
days O
) O
after O
the O
initiation O
of O
chemotherapy O
. O

Plasma O
ammonium B
level O
ranged O
from O
248 O
to O
2387 O
microg O
% O
( O
mean O
: O
626 O
+ O
/ O
- O
431 O
microg O
% O
) O
. O

Among O
the O
32 O
episodes O
, O
26 O
( O
81 O
% O
) O
had O
various O
degrees O
of O
azotemia O
, O
18 O
( O
56 O
% O
) O
occurred O
during O
bacterial O
infections O
and O
14 O
( O
44 O
% O
) O
without O
infection O
occurred O
during O
periods O
of O
dehydration O
. O

Higher O
plasma O
ammonium B
levels O
and O
more O
rapid O
onset O
of O
hyperammonemia O
were O
seen O
in O
18 O
patients O
with O
bacterial O
infections O
( O
p O
= O
0 O
. O
003 O
and O
0 O
. O
0006 O
, O
respectively O
) O
and O
in O
nine O
patients O
receiving O
high O
daily O
doses O
( O
2600 O
or O
1800 O
mg O
/ O
m2 O
) O
of O
5 B
- I
FU I
( O
p O
= O
0 O
. O
0001 O
and O
< O
0 O
. O
0001 O
, O
respectively O
) O
. O

In O
25 O
out O
of O
32 O
episodes O
( O
78 O
% O
) O
, O
plasma O
ammonium B
levels O
and O
mental O
status O
returned O
to O
normal O
within O
2 O
days O
after O
adequate O
management O
. O

In O
conclusion O
, O
hyperammonemic O
encephalopathy O
can O
occur O
in O
patients O
receiving O
continuous O
infusion O
of O
5 B
- I
FU I
. O

Azotemia O
, O
body O
fluid O
insufficiency O
and O
bacterial O
infections O
were O
frequently O
found O
in O
these O
patients O
. O

It O
is O
therefore O
important O
to O
recognize O
this O
condition O
in O
patients O
receiving O
continuous O
infusion O
of O
5 B
- I
FU I
. O

The O
effects O
of O
quinine B
and O
4 B
- I
aminopyridine I
on O
conditioned O
place O
preference O
and O
changes O
in O
motor O
activity O
induced O
by O
morphine B
in O
rats O
. O

1 O
. O

The O
effects O
of O
two O
unselective O
potassium B
( O
K B
( O
+ O
) O
- O
) O
channel O
blockers O
, O
quinine B
( O
12 O
. O
5 O
, O
25 O
and O
50 O
mg O
/ O
kg O
) O
and O
4 B
- I
aminopyridine I
( O
1 O
and O
2 O
mg O
/ O
kg O
) O
, O
on O
conditioned O
place O
preference O
and O
biphasic O
changes O
in O
motor O
activity O
induced O
by O
morphine B
( O
10 O
mg O
/ O
kg O
) O
were O
tested O
in O
Wistar O
rats O
. O

Quinine B
is O
known O
to O
block O
voltage O
- O
, O
calcium B
- O
and O
ATP B
- O
sensitive O
K B
( O
+ O
) O
- O
channels O
while O
4 B
- I
aminopyridine I
is O
known O
to O
block O
voltage O
- O
sensitive O
K B
( O
+ O
) O
- O
channels O
. O

2 O
. O

In O
the O
counterbalanced O
method O
, O
quinine B
attenuated O
morphine B
- O
induced O
place O
preference O
, O
whereas O
4 B
- I
aminopyridine I
was O
ineffective O
. O

In O
the O
motor O
activity O
test O
measured O
with O
an O
Animex O
- O
activity O
meter O
neither O
of O
the O
K B
( O
+ O
) O
- O
channel O
blockers O
affected O
morphine B
- O
induced O
hypoactivity O
, O
but O
both O
K B
( O
+ O
) O
- O
channel O
blockers O
prevented O
morphine B
- O
induced O
secondary O
hyperactivity O
. O

3 O
. O

These O
results O
suggest O
the O
involvement O
of O
quinine B
- O
sensitive O
but O
not O
4 B
- I
aminopyridine I
- O
sensitive O
K B
( O
+ O
) O
- O
channels O
in O
morphine B
reward O
. O

It O
is O
also O
suggested O
that O
the O
blockade O
of O
K B
( O
+ O
) O
- O
channels O
sensitive O
to O
these O
blockers O
is O
not O
sufficient O
to O
prevent O
morphine B
- O
induced O
hypoactivity O
whereas O
morphine B
- O
induced O
hyperactivity O
seems O
to O
be O
connected O
to O
both O
quinine B
- O
and O
4 B
- I
aminopyridine I
- O
sensitive O
K B
( O
+ O
) O
- O
channels O
. O

Nociceptin B
/ I
orphanin I
FQ I
and O
nocistatin B
on O
learning O
and O
memory O
impairment O
induced O
by O
scopolamine B
in O
mice O
. O

1 O
. O

Nociceptin B
, O
also O
known O
as O
orphanin B
FQ I
, O
is O
an O
endogenous O
ligand O
for O
the O
orphan O
opioid O
receptor O
- O
like O
receptor O
1 O
( O
ORL1 O
) O
and O
involves O
in O
various O
functions O
in O
the O
central O
nervous O
system O
( O
CNS O
) O
. O

On O
the O
other O
hand O
, O
nocistatin B
is O
recently O
isolated O
from O
the O
same O
precursor O
as O
nociceptin B
and O
blocks O
nociceptin B
- O
induced O
allodynia O
and O
hyperalgesia O
. O

2 O
. O

Although O
ORL1 O
receptors O
which O
display O
a O
high O
degree O
of O
sequence O
homology O
with O
classical O
opioid O
receptors O
are O
abundant O
in O
the O
hippocampus O
, O
little O
is O
known O
regarding O
their O
role O
in O
learning O
and O
memory O
. O

3 O
. O

The O
present O
study O
was O
designed O
to O
investigate O
whether O
nociceptin B
/ I
orphanin I
FQ I
and O
nocistatin B
could O
modulate O
impairment O
of O
learning O
and O
memory O
induced O
by O
scopolamine B
, O
a O
muscarinic O
cholinergic O
receptor O
antagonist O
, O
using O
spontaneous O
alternation O
of O
Y O
- O
maze O
and O
step O
- O
down O
type O
passive O
avoidance O
tasks O
in O
mice O
. O

4 O
. O

While O
nocistatin B
( O
0 O
. O
5 O
- O
5 O
. O
0 O
nmol O
mouse O
- O
1 O
, O
i O
. O
c O
. O
v O
. O
) O
administered O
30 O
min O
before O
spontaneous O
alternation O
performance O
or O
the O
training O
session O
of O
the O
passive O
avoidance O
task O
, O
had O
no O
effect O
on O
spontaneous O
alternation O
or O
passive O
avoidance O
behaviours O
, O
a O
lower O
per O
cent O
alternation O
and O
shorter O
median O
step O
- O
down O
latency O
in O
the O
retention O
test O
were O
obtained O
in O
nociceptin B
( O
1 O
. O
5 O
and O
/ O
or O
5 O
. O
0 O
nmol O
mouse O
- O
1 O
, O
i O
. O
c O
. O
v O
. O
) O
- O
treated O
normal O
mice O
. O

5 O
. O

Administration O
of O
nocistatin B
( O
1 O
. O
5 O
and O
/ O
or O
5 O
. O
0 O
nmol O
mouse O
- O
1 O
, O
i O
. O
c O
. O
v O
. O
) O
30 O
min O
before O
spontaneous O
alternation O
performance O
or O
the O
training O
session O
of O
the O
passive O
avoidance O
task O
, O
attenuated O
the O
scopolamine B
- O
induced O
impairment O
of O
spontaneous O
alternation O
and O
passive O
avoidance O
behaviours O
. O

6 O
. O

These O
results O
indicated O
that O
nocistatin B
, O
a O
new O
biologically O
active O
peptide O
, O
ameliorates O
impairments O
of O
spontaneous O
alternation O
and O
passive O
avoidance O
induced O
by O
scopolamine B
, O
and O
suggested O
that O
these O
peptides O
play O
opposite O
roles O
in O
learning O
and O
memory O
. O

Meloxicam B
- O
induced O
liver O
toxicity O
. O

We O
report O
the O
case O
of O
a O
female O
patient O
with O
rheumatoid O
arthritis O
who O
developed O
acute O
cytolytic O
hepatitis O
due O
to O
meloxicam B
. O

Recently O
introduced O
in O
Belgium O
, O
meloxicam B
is O
the O
first O
nonsteroidal O
antiinflammatory O
drug O
with O
selective O
action O
on O
the O
inducible O
form O
of O
cyclooxygenase O
2 O
. O

The O
acute O
cytolytic O
hepatitis O
occurred O
rapidly O
after O
meloxicam B
administration O
and O
was O
associated O
with O
the O
development O
of O
antinuclear O
antibodies O
suggesting O
a O
hypersensitivity O
mechanism O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Catalepsy O
was O
evaluated O
at O
the O
beginning O
and O
the O
end O
of O
the O
treatments O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Anorexigens O
and O
pulmonary O
hypertension O
in O
the O
United O
States O
: O
results O
from O
the O
surveillance O
of O
North O
American O
pulmonary O
hypertension O
. O

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

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

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

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

Patients O
with O
no O
identifiable O
cause O
of O
pulmonary O
hypertension O
were O
classed O
as O
PPH O
. O

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

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

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

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

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

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

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

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

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

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

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

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

Bleeding O
is O
the O
primary O
untoward O
effect O
of O
heparin B
. O

Major O
bleeding O
is O
of O
primary O
concern O
in O
patients O
receiving O
heparin B
therapy O
. O

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

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

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

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

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

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

METHOD O
: O
Case O
report O
. O

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

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

Deterioration O
of O
vision O
occurred O
despite O
discontinuation O
of O
the O
tacrolimus B
. O

CONCLUSION O
: O
Tacrolimus B
and O
other O
immunosuppressive O
agents O
may O
be O
associated O
with O
optic O
nerve O
toxicity O
. O

Hypercalcemia O
, O
arrhythmia O
, O
and O
mood O
stabilizers O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Patterns O
of O
sulfadiazine B
acute O
nephrotoxicity O
. O

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

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

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

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

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

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

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

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

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

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

Downbeat O
nystagmus O
associated O
with O
intravenous O
patient O
- O
controlled O
administration O
of O
morphine B
. O

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

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

Hemodynamic O
and O
antiadrenergic O
effects O
of O
dronedarone B
and O
amiodarone B
in O
animals O
with O
a O
healed O
myocardial O
infarction O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

One O
patient O
developed O
grade O
3 O
diarrhea O
requiring O
hospitalization O
for O
hydration O
. O

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

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

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

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

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

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

The O
Olanzipine B
HGGW O
Study O
Group O
. O

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

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

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

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

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

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

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

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

There O
were O
no O
statistically O
significant O
differences O
in O
EPSs O
between O
groups O
. O

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

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

The O
effect O
of O
pupil O
dilation O
with O
tropicamide B
on O
vision O
and O
driving O
simulator O
performance O
. O

PURPOSE O
: O
To O
assess O
the O
effect O
of O
pupil O
dilation O
on O
vision O
and O
driving O
ability O
. O

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

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

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

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

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

RESULTS O
: O
Pupillary O
dilation O
resulted O
in O
a O
statistically O
significant O
deterioration O
in O
CT O
and O
HCVA O
only O
. O

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

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

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

CONCLUSIONS O
: O
Pupillary O
dilation O
may O
lead O
to O
a O
decrease O
in O
vision O
and O
daylight O
driving O
performance O
in O
young O
people O
. O

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

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

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

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

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

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

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

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

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

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

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

Hyperglycemic O
effect O
of O
amino O
compounds O
structurally O
related O
to O
caproate B
in O
rats O
. O

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

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

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

The O
Assessment O
of O
Treatment O
with O
Lisinopril B
and O
Survival O
. O

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

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

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

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

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

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

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

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

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

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

Cocaine B
, O
ethanol B
, O
and O
cocaethylene B
cardiotoxity O
in O
an O
animal O
model O
of O
cocaine O
and O
ethanol B
abuse O
. O

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

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

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

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

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

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

RESULTS O
: O
Two O
of O
eight O
dogs O
in O
the O
C O
+ O
E O
group O
experienced O
cardiovascular O
collapse O
. O

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

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

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

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

Co O
- O
administration O
resulted O
in O
prolonged O
cardiac O
toxicity O
and O
was O
dysrhythmogenic O
. O

Peak O
serum O
cocaethylene B
concentrations O
were O
associated O
with O
prolonged O
myocardial O
depression O
. O

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

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

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

Viracept O
and O
irregular O
heartbeat O
warning O
. O

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

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

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

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

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

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

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

Therefore O
, O
we O
sought O
to O
address O
these O
parameters O
in O
patients O
with O
Graves O
' O
disease O
. O

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

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

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

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

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

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

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

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

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

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

Prevalence O
of O
heart O
disease O
in O
asymptomatic O
chronic O
cocaine B
users O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

STUDY O
OBJECTIVE O
: O
Chest O
pain O
in O
the O
setting O
of O
cocaine B
use O
poses O
a O
diagnostic O
dilemma O
. O

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

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

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

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

Patients O
exhibiting O
signs O
of O
continuing O
cocaine B
toxicity O
were O
excluded O
from O
the O
study O
. O

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

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

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

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

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

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

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

Prenatal O
cocaine B
exposure O
and O
cranial O
sonographic O
findings O
in O
preterm O
infants O
. O

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

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

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

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

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

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

The O
incidence O
of O
subependymal O
cysts O
in O
the O
117 O
remaining O
infants O
was O
14 O
% O
( O
16 O
of O
117 O
) O
. O

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

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

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

Thalidomide B
neuropathy O
in O
patients O
treated O
for O
metastatic O
prostate O
cancer O
. O

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

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

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

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

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

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

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

Six O
patients O
developed O
neuropathy O
. O

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

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

Neuropathy O
may O
thus O
be O
a O
common O
complication O
of O
thalidomide B
in O
older O
patients O
. O

The O
SNAP O
index O
can O
be O
used O
to O
monitor O
peripheral O
neuropathy O
, O
but O
not O
for O
early O
detection O
. O

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

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

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

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

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

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

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

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

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

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

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

Fatty O
liver O
induced O
by O
tetracycline B
in O
the O
rat O
. O

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

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

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

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

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

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

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

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

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

Prednisone B
induces O
anxiety O
and O
glial O
cerebral O
changes O
in O
rats O
. O

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

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

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

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

In O
the O
control O
group O
implants O
contained O
no O
PDN O
. O

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

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

RESULTS O
: O
Anxiety O
was O
documented O
in O
both O
groups O
of O
PDN O
treated O
rats O
compared O
with O
controls O
. O

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

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

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

CONCLUSION O
: O
Subacute O
exposure O
to O
PDN O
induced O
anxiety O
and O
reactivity O
of O
microglia O
. O

The O
relevance O
of O
these O
features O
for O
patients O
using O
PDN O
remains O
to O
be O
elucidated O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Cotrimoxazole B
, O
metronidazole B
, O
and O
erythromycin B
were O
involved O
in O
15 O
reported O
manic O
episodes O
. O

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

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

Patients O
have O
an O
increased O
risk O
of O
developing O
mania O
while O
being O
treated O
with O
antimicrobials O
. O

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

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

The O
authors O
elected O
to O
name O
this O
syndrome O
" O
antibiomania O
. O
" O

Levodopa B
- O
induced O
ocular O
dyskinesias O
in O
Parkinson O
' O
s O
disease O
. O

Levodopa B
- O
induced O
ocular O
dyskinesias O
are O
very O
uncommon O
. O

Usually O
they O
occur O
simultaneously O
with O
limb O
peak O
- O
dose O
choreatic O
dyskinesias O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

Low O
back O
pain O
was O
also O
relieved O
by O
both O
drugs O
. O

Headache O
was O
significantly O
increased O
by O
GTN B
but O
not O
by O
DCF B
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Pulmonary O
hypertension O
after O
ibuprofen B
prophylaxis O
in O
very O
preterm O
infants O
. O

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

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

Hypoxaemia O
resolved O
quickly O
on O
inhaled O
nitric B
oxide I
therapy O
. O

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

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

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

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

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

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

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

Approximately O
75 O
% O
of O
the O
patients O
were O
receiving O
treatment O
for O
leukemia O
or O
lymphoma O
. O

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

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

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

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

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

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

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

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

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

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

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

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

Delayed O
cystitis O
still O
persisted O
in O
DBA O
/ O
2 O
mice O
100 O
days O
after O
treatment O
. O

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

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

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

A O
phase O
II O
study O
. O

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

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

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

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

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

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

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

18 O
patients O
had O
a O
primary O
AGC O
, O
and O
15 O
showed O
a O
relapsed O
AGC O
. O

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

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

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

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

Two O
patients O
developed O
hemolytic O
- O
uremic O
syndrome O
( O
HUS O
) O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

In O
4 O
children O
, O
indinavir B
was O
discontinued O
because O
of O
nephrotoxicity O
. O

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

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

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

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

The O
impairment O
of O
the O
renal O
function O
in O
these O
children O
occurred O
in O
the O
absence O
of O
clinical O
symptoms O
of O
nephrolithiasis O
. O

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

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

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

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

OBJECTIVE O
: O
To O
assess O
outcomes O
based O
on O
troponin O
positivity O
in O
patients O
with O
cocaine O
chest O
pain O
admitted O
for O
exclusion O
of O
MI O
. O

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

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

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

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

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

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

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

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

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

Acute O
interstitial O
nephritis O
due O
to O
nicergoline B
( O
Sermion B
) O
. O

We O
report O
a O
case O
of O
acute O
interstitial O
nephritis O
( O
AIN O
) O
due O
to O
nicergoline B
( O
Sermion B
) O
. O

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

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

Thereafter O
, O
he O
experienced O
intermittent O
fever O
and O
skin O
rash O
. O

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

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

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

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

Neuroleptic O
malignant O
syndrome O
complicated O
by O
massive O
intestinal O
bleeding O
in O
a O
patient O
with O
chronic O
renal O
failure O
. O

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

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

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

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

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

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

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

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

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

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

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

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

Carvedilol B
protects O
against O
doxorubicin B
- O
induced O
mitochondrial O
cardiomyopathy O
. O

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

Recent O
evidence O
indicates O
that O
oxidative O
stress O
and O
mitochondrial O
dysfunction O
are O
key O
factors O
in O
the O
pathogenic O
process O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Evidence O
of O
peripheral O
sensory O
neuropathy O
was O
found O
in O
nine O
of O
13 O
men O
before O
treatment O
. O

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

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

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

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

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

We O
describe O
2 O
cases O
of O
grand O
mal O
seizures O
following O
accidental O
intravascular O
injection O
of O
levobupivacaine B
. O

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

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

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

Neither O
patient O
developed O
signs O
of O
cardiovascular O
toxicity O
. O

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

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

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

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

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

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

Transient O
prolongation O
of O
the O
QT O
during O
bladder O
irrigation O
prompted O
the O
episode O
of O
TdP O
. O

It O
is O
well O
known O
that O
bradycardia O
exacerbates O
acquired O
TdP O
. O

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

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

Anaesthetic O
complications O
associated O
with O
myotonia O
congenita O
: O
case O
study O
and O
comparison O
with O
other O
myotonic O
disorders O
. O

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

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

The O
muscle O
spasms O
disappeared O
spontaneously O
and O
the O
surgery O
proceeded O
without O
further O
problems O
. O

When O
subsequently O
questioned O
, O
she O
reported O
minor O
symptoms O
suggesting O
a O
myotonic O
condition O
. O

Myotonia O
was O
found O
on O
clinical O
examination O
and O
EMG O
. O

The O
diagnosis O
MC O
was O
confirmed O
genetically O
. O

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

We O
give O
a O
brief O
overview O
of O
ion O
channel O
disorders O
including O
malignant O
hyperthermia O
and O
their O
anaesthetic O
considerations O
. O

Respiratory O
pattern O
in O
a O
rat O
model O
of O
epilepsy O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

Fatal O
myeloencephalopathy O
due O
to O
intrathecal O
vincristine B
administration O
. O

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

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

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

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

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

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

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

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

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

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

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

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

Increased O
serum O
soluble O
Fas O
in O
patients O
with O
acute O
liver O
failure O
due O
to O
paracetamol B
overdose O
. O

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

The O
aim O
of O
the O
study O
was O
to O
investigate O
the O
soluble O
form O
of O
Fas O
in O
patients O
with O
acute O
liver O
failure O
. O

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

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

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

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

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

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

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

Bilateral O
subthalamic O
nucleus O
stimulation O
for O
Parkinson O
' O
s O
disease O
. O

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

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

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

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

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

The O
subscores O
for O
the O
akinesia O
, O
rigidity O
, O
tremor O
and O
gait O
also O
improved O
. O

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

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

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

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

CONCLUSION O
: O
Bilateral O
subthalamic O
nucleus O
stimulation O
is O
an O
effective O
treatment O
for O
advanced O
Parkinson O
' O
s O
disease O
. O

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

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

Acute O
renal O
failure O
occurring O
during O
intravenous O
desferrioxamine B
therapy O
: O
recovery O
after O
haemodialysis O
. O

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

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

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

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

Ocular O
motility O
changes O
after O
subtenon O
carboplatin B
chemotherapy O
for O
retinoblastoma O
. O

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

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

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

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

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

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

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

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

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

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

Ethambutol B
and O
optic O
neuropathy O
. O

PURPOSE O
: O
To O
demonstrate O
the O
association O
between O
ethambutol B
and O
optic O
neuropathy O
. O

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

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

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

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

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

CONCLUSION O
: O
Early O
recognition O
of O
optic O
neuropathy O
should O
be O
considered O
in O
patients O
with O
ethambutol B
therapy O
. O

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

Treatment O
of O
compensatory O
gustatory O
hyperhidrosis O
with O
topical O
glycopyrrolate B
. O

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

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

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

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

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

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

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

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

Neuroleptic O
- O
associated O
hyperprolactinemia O
. O

Can O
it O
be O
treated O
with O
bromocriptine B
? O

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

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

One O
woman O
, O
however O
, O
developed O
worsened O
psychiatric O
symptoms O
while O
taking O
bromocriptine B
, O
and O
it O
was O
discontinued O
. O

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

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

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

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

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

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

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

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

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

These O
effects O
were O
similar O
to O
those O
induced O
by O
diazepam B
, O
whereas O
the O
partial O
agonist O
Ro B
16 I
- I
6028 I
( O
tert B
- I
butyl I
- I
( I
S I
) I
- I
8 I
- I
bromo I
- I
11 I
, I
12 I
, I
13 I
, I
13a I
- I
tetrahydro I
- I
9 I
- I
oxo I
- I
9H I
- I
imidazo I
[ I
1 I
, I
5 I
- I
a I
] I
- I
pyrrolo I
- I
[ I
2 I
, I
1 I
- I
c I
] I
[ I
1 I
, I
4 I
] I
benzodiazepine I
- I
1 I
- I
carboxylate I
) O
showed O
very O
weak O
efficacy O
in O
these O
biochemical O
tests O
. O

After O
i O
. O
p O
. O
injection O
to O
rats O
, O
abecarnil B
and O
diazepam B
decreased O
in O
a O
time O
- O
dependent O
and O
dose O
- O
related O
( O
0 O
. O
25 O
- O
20 O
mg O
/ O
kg O
i O
. O
p O
. O
) O
manner O
[ O
35S O
] O
TBPS O
binding O
measured O
ex O
vivo O
in O
the O
cerebral O
cortex O
. O

Moreover O
, O
both O
drugs O
at O
the O
dose O
of O
0 O
. O
5 O
mg O
/ O
kg O
antagonized O
completely O
the O
convulsant O
activity O
and O
the O
increase O
of O
[ O
35S O
] O
TBPS O
binding O
induced O
by O
isoniazide B
( O
350 O
mg O
/ O
kg O
s O
. O
c O
. O
) O
as O
well O
as O
the O
increase O
of O
[ O
35S O
] O
TBPS O
binding O
induced O
by O
foot O
- O
shock O
stress O
. O

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

In O
these O
animals O
, O
abecarnil B
produced O
a O
paralleled O
dose O
- O
dependent O
( O
0 O
. O
05 O
- O
1 O
mg O
/ O
kg O
i O
. O
p O
. O
) O
reduction O
of O
both O
motor O
behavior O
and O
cortical O
[ O
35S O
] O
TBPS O
binding O
. O

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

Recurrent O
myocardial O
infarction O
in O
a O
postpartum O
patient O
receiving O
bromocriptine B
. O

Myocardial O
infarction O
in O
puerperium O
is O
infrequently O
reported O
. O

Spasm O
, O
coronary O
dissection O
, O
or O
atheromatous O
etiology O
has O
been O
described O
. O

Bromocriptine B
has O
been O
implicated O
in O
several O
previous O
case O
reports O
of O
myocardial O
infarction O
in O
the O
puerperium O
. O

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

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

Asterixis O
induced O
by O
carbamazepine B
therapy O
. O

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

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

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

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

Pharmacodynamics O
of O
the O
hypotensive O
effect O
of O
levodopa B
in O
parkinsonian O
patients O
. O

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

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

Stable O
responders O
demonstrated O
a O
small O
hypotensive O
response O
. O

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

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

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

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

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

Syndrome O
of O
inappropriate O
secretion O
of O
antidiuretic O
hormone O
after O
infusional O
vincristine B
. O

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

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

Evaluation O
revealed O
the O
syndrome O
of O
inappropriate O
secretion O
of O
antidiuretic O
hormone O
, O
which O
was O
attributed O
to O
the O
vincristine B
infusion O
. O

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

Heart O
failure O
: O
to O
digitalise B
or O
not O
? O

The O
view O
against O
. O

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

In O
patients O
with O
atrial O
fibrillation O
digoxin B
is O
beneficial O
for O
ventricular O
rate O
control O
. O

For O
patients O
in O
sinus O
rhythm O
and O
heart O
failure O
the O
situation O
is O
less O
clear O
. O

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

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

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

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

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

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

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

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

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

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

Isradipine B
treatment O
for O
hypertension O
in O
general O
practice O
in O
Hong O
Kong O
. O

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

303 O
Chinese O
patients O
with O
mild O
to O
moderate O
hypertension O
entered O
the O
study O
. O

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

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

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

Similar O
reductions O
occurred O
in O
standing O
blood O
pressure O
and O
there O
was O
no O
evidence O
of O
postural O
hypotension O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

Pure O
red O
cell O
aplasia O
, O
toxic O
dermatitis O
and O
lymphadenopathy O
in O
a O
patient O
taking O
diphenylhydantoin B
. O

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

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

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

Pure O
red O
cell O
aplasia O
associated O
with O
diphenylhydantoin B
medication O
has O
been O
reported O
in O
3 O
patients O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

MRI O
findings O
of O
hypoxic O
cortical O
laminar O
necrosis O
in O
a O
child O
with O
hemolytic O
anemia O
crisis O
. O

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

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

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

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

The O
natural O
history O
of O
Vigabatrin B
associated O
visual O
field O
defects O
in O
patients O
electing O
to O
continue O
their O
medication O
. O

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

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

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

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

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

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

Only O
one O
patient O
demonstrated O
a O
deterioration O
in O
visual O
field O
during O
the O
study O
period O
and O
discontinued O
treatment O
. O

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

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

Induction O
of O
rosaceiform O
dermatitis O
during O
treatment O
of O
facial O
inflammatory O
dermatoses O
with O
tacrolimus B
ointment O
. O

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

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

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

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

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

In O
1 O
patient O
with O
eyelid O
eczema O
, O
rosaceiform O
periocular O
dermatitis O
gradually O
appeared O
after O
3 O
weeks O
of O
treatment O
. O

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

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

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

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

Intravascular O
hemolysis O
and O
acute O
renal O
failure O
following O
intermittent O
rifampin B
therapy O
. O

Renal O
failure O
is O
a O
rare O
complication O
associated O
with O
the O
use O
of O
rifampin B
. O

Intravascular O
hemolysis O
leading O
to O
acute O
renal O
failure O
following O
rifampin B
therapy O
is O
extremely O
rare O
. O

Two O
patients O
with O
leprosy O
who O
developed O
hemolysis O
and O
acute O
renal O
failure O
following O
rifampin B
are O
reported O
. O

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Patients O
also O
received O
dietary O
counseling O
, O
educational O
materials O
, O
and O
reminders O
to O
call O
a O
toll O
- O
free O
number O
that O
provided O
further O
education O
about O
dyslipidemia O
and O
niacin B
extended O
- O
release O
/ O
lovastatin B
. O

Primary O
end O
points O
were O
study O
compliance O
, O
increases O
in O
liver O
transaminases O
to O
> O
3 O
times O
the O
upper O
limit O
of O
normal O
, O
and O
clinical O
myopathy O
. O

Final O
study O
status O
was O
available O
for O
4 O
, O
217 O
patients O
( O
94 O
% O
) O
. O

Compliance O
to O
niacin B
extended O
- O
release O
/ O
lovastatin B
was O
77 O
% O
, O
with O
3 O
, O
245 O
patients O
completing O
the O
study O
. O

Patients O
in O
the O
southeast O
and O
those O
enrolled O
by O
endocrinologists O
had O
the O
lowest O
compliance O
and O
highest O
adverse O
event O
rates O
. O

Flushing O
was O
the O
most O
common O
adverse O
event O
, O
reported O
by O
18 O
% O
of O
patients O
and O
leading O
to O
discontinuation O
by O
6 O
% O
. O

Incidence O
of O
increased O
aspartate B
aminotransferase O
and O
/ O
or O
alanine B
aminotransferase O
> O
3 O
times O
the O
upper O
limit O
of O
normal O
was O
< O
0 O
. O
3 O
% O
. O

An O
increase O
of O
creatine B
phosphokinase O
to O
> O
5 O
times O
the O
upper O
limit O
of O
normal O
occurred O
in O
0 O
. O
24 O
% O
of O
patients O
, O
and O
no O
cases O
of O
drug O
- O
induced O
myopathy O
were O
observed O
. O

Niacin B
extended O
- O
release O
/ O
lovastatin B
1 O
, O
000 O
/ O
40 O
mg O
, O
dosed O
as O
initial O
therapy O
, O
was O
associated O
with O
good O
compliance O
and O
safety O
and O
had O
very O
low O
incidences O
of O
increased O
liver O
and O
muscle O
enzymes O
. O

Protective O
effect O
of O
Terminalia O
chebula O
against O
experimental O
myocardial O
injury O
induced O
by O
isoproterenol B
. O

Cardioprotective O
effect O
of O
ethanolic O
extract O
of I
Terminalia I
chebula I
fruits O
( O
500 O
mg O
/ O
kg O
body O
wt O
) O
was O
examined O
in O
isoproterenol B
( O
200 O
mg O
/ O
kg O
body O
wt O
) O
induced O
myocardial O
damage O
in O
rats O
. O

In O
isoproterenol B
administered O
rats O
, O
the O
level O
of O
lipid O
peroxides O
increased O
significantly O
in O
the O
serum O
and O
heart O
. O

A O
significant O
decrease O
was O
observed O
in O
the O
activity O
of O
the O
myocardial O
marker O
enzymes O
with O
a O
concomitant O
increase O
in O
their O
activity O
in O
serum O
. O

Histopathological O
examination O
was O
carried O
out O
to O
confirm O
the O
myocardial O
necrosis O
. O

T B
. I
chebula I
extract I
pretreatment O
was O
found O
to O
ameliorate O
the O
effect O
of O
isoproterenol B
on O
lipid O
peroxide O
formation O
and O
retained O
the O
activities O
of O
the O
diagnostic O
marker O
enzymes O
. O

A O
case O
of O
postoperative O
anxiety O
due O
to O
low O
dose O
droperidol B
used O
with O
patient O
- O
controlled O
analgesia O
. O

A O
multiparous O
woman O
in O
good O
psychological O
health O
underwent O
urgent O
caesarean O
section O
in O
labour O
. O

Postoperatively O
, O
she O
was O
given O
a O
patient O
- O
controlled O
analgesia O
device O
delivering O
boluses O
of O
diamorphine B
0 O
. O
5 O
mg O
and O
droperidol B
0 O
. O
025 O
mg O
. O

Whilst O
using O
the O
device O
she O
gradually O
became O
anxious O
, O
the O
feeling O
worsening O
after O
each O
bolus O
. O

The O
diagnosis O
of O
droperidol B
- O
induced O
psychological O
disturbance O
was O
not O
made O
straight O
away O
although O
on O
subsequent O
close O
questioning O
the O
patient O
gave O
a O
very O
clear O
history O
. O

After O
she O
had O
received O
a O
total O
of O
only O
0 O
. O
9 O
mg O
droperidol B
, O
a O
syringe O
containing O
diamorphine B
only O
was O
substituted O
and O
her O
unease O
resolved O
completely O
. O

We O
feel O
that O
, O
although O
the O
dramatic O
extrapyramidal O
side O
effects O
of O
dopaminergic O
antiemetics O
are O
well O
known O
, O
more O
subtle O
manifestations O
may O
easily O
be O
overlooked O
. O

Accurate O
patient O
history O
contributes O
to O
differentiating O
diabetes O
insipidus O
: O
a O
case O
study O
. O

This O
case O
study O
highlights O
the O
important O
contribution O
of O
nursing O
in O
obtaining O
an O
accurate O
health O
history O
. O

The O
case O
discussed O
herein O
initially O
appeared O
to O
be O
neurogenic O
diabetes O
insipidus O
( O
DI O
) O
secondary O
to O
a O
traumatic O
brain O
injury O
. O

The O
nursing O
staff O
, O
by O
reviewing O
the O
patient O
' O
s O
health O
history O
with O
his O
family O
, O
discovered O
a O
history O
of O
polydipsia O
and O
long O
- O
standing O
lithium B
use O
. O

Lithium B
is O
implicated O
in O
drug O
- O
induced O
nephrogenic O
DI O
, O
and O
because O
the O
patient O
had O
not O
received O
lithium B
since O
being O
admitted O
to O
the O
hospital O
, O
his O
treatment O
changed O
to O
focus O
on O
nephrogenic O
DI O
. O

By O
combining O
information O
from O
the O
patient O
history O
, O
the O
physical O
examination O
, O
and O
radiologic O
and O
laboratory O
studies O
, O
the O
critical O
care O
team O
demonstrated O
that O
the O
patient O
had O
been O
self O
- O
treating O
his O
lithium B
- O
induced O
nephrogenic O
DI O
and O
developed O
neurogenic O
DI O
secondary O
to O
brain O
trauma O
. O

Thus O
successful O
treatment O
required O
that O
nephrogenic O
and O
neurogenic O
DI O
be O
treated O
concomitantly O
. O

Factors O
contributing O
to O
ribavirin B
- O
induced O
anemia O
. O

BACKGROUND O
AND O
AIM O
: O
Interferon B
and O
ribavirin B
combination O
therapy O
for O
chronic O
hepatitis O
C O
produces O
hemolytic O
anemia O
. O

This O
study O
was O
conducted O
to O
identify O
the O
factors O
contributing O
to O
ribavirin B
- O
induced O
anemia O
. O

METHODS O
: O
Eighty O
- O
eight O
patients O
with O
chronic O
hepatitis O
C O
who O
received O
interferon B
- I
alpha I
- I
2b I
at O
a O
dose O
of O
6 O
MU O
administered O
intramuscularly O
for O
24 O
weeks O
in O
combination O
with O
ribavirin B
administered O
orally O
at O
a O
dose O
of O
600 O
mg O
or O
800 O
mg O
participated O
in O
the O
study O
. O

A O
hemoglobin O
concentration O
of O
< O
10 O
g O
/ O
dL O
was O
defined O
as O
ribavirin B
- O
induced O
anemia O
. O

RESULTS O
: O
Ribavirin B
- O
induced O
anemia O
occurred O
in O
18 O
( O
20 O
. O
5 O
% O
) O
patients O
during O
treatment O
. O

A O
2 O
g O
/ O
dL O
decrease O
in O
hemoglobin O
concentrations O
in O
patients O
with O
anemia O
was O
observed O
at O
week O
2 O
after O
the O
start O
of O
treatment O
. O

The O
hemoglobin O
concentration O
in O
patients O
with O
> O
or O
= O
2 O
g O
/ O
dL O
decrease O
at O
week O
2 O
was O
observed O
to O
be O
significantly O
lower O
even O
after O
week O
2 O
than O
in O
patients O
with O
< O
2 O
g O
/ O
dL O
decrease O
( O
P O
< O
0 O
. O
01 O
) O
. O

A O
significant O
relationship O
was O
observed O
between O
the O
rate O
of O
reduction O
of O
hemoglobin O
concentrations O
at O
week O
2 O
and O
the O
severity O
of O
anemia O
( O
P O
< O
0 O
. O
01 O
) O
. O

Such O
factors O
as O
sex O
( O
female O
) O
, O
age O
( O
> O
or O
= O
60 O
years O
old O
) O
, O
and O
the O
ribavirin B
dose O
by O
body O
weight O
( O
12 O
mg O
/ O
kg O
or O
more O
) O
were O
significant O
by O
univariate O
analysis O
. O

CONCLUSIONS O
: O
Careful O
administration O
is O
necessary O
in O
patients O
> O
or O
= O
60 O
years O
old O
, O
in O
female O
patients O
, O
and O
in O
patients O
receiving O
a O
ribavirin B
dose O
of O
12 O
mg O
/ O
kg O
or O
more O
. O

Patients O
who O
experience O
a O
fall O
in O
hemoglobin O
concentrations O
of O
2 O
g O
/ O
dL O
or O
more O
at O
week O
2 O
after O
the O
start O
of O
treatment O
should O
be O
monitored O
with O
particular O
care O
. O

Zidovudine B
- O
induced O
hepatitis O
. O

A O
case O
of O
acute O
hepatitis O
induced O
by O
zidovudine B
in O
a O
38 O
- O
year O
- O
old O
patient O
with O
AIDS O
is O
presented O
. O

The O
mechanism O
whereby O
the O
hepatitis O
was O
induced O
is O
not O
known O
. O

However O
, O
the O
patient O
tolerated O
well O
an O
alternative O
reverse O
transcriptase O
inhibitor O
, O
2 B
' I
3 I
' I
dideoxyinosine I
. O

Physicians O
caring O
for O
patients O
with O
AIDS O
should O
be O
aware O
of O
this O
hitherto O
rarely O
reported O
complication O
. O

Oxidative O
damage O
precedes O
nitrative O
damage O
in O
adriamycin B
- O
induced O
cardiac O
mitochondrial O
injury O
. O

The O
purpose O
of O
the O
present O
study O
was O
to O
determine O
if O
elevated O
reactive O
oxygen B
( O
ROS O
) O
/ O
nitrogen B
species O
( O
RNS O
) O
reported O
to O
be O
present O
in O
adriamycin B
( O
ADR B
) O
- O
induced O
cardiotoxicity O
actually O
resulted O
in O
cardiomyocyte O
oxidative O
/ O
nitrative O
damage O
, O
and O
to O
quantitatively O
determine O
the O
time O
course O
and O
subcellular O
localization O
of O
these O
postulated O
damage O
products O
using O
an O
in O
vivo O
approach O
. O

B6C3 O
mice O
were O
treated O
with O
a O
single O
dose O
of O
20 O
mg O
/ O
kg O
ADR B
. O

Ultrastructural O
damage O
and O
levels O
of O
4 B
- I
hydroxy I
- I
2 I
- I
nonenal I
( O
4HNE B
) O
- O
protein O
adducts O
and O
3 B
- I
nitrotyrosine I
( O
3NT B
) O
were O
analyzed O
. O

Quantitative O
ultrastructural O
damage O
using O
computerized O
image O
techniques O
showed O
cardiomyocyte O
injury O
as O
early O
as O
3 O
hours O
, O
with O
mitochondria O
being O
the O
most O
extensively O
and O
progressively O
injured O
subcellular O
organelle O
. O

Analysis O
of O
4HNE B
protein O
adducts O
by O
immunogold O
electron O
microscopy O
showed O
appearance O
of O
4HNE B
protein O
adducts O
in O
mitochondria O
as O
early O
as O
3 O
hours O
, O
with O
a O
peak O
at O
6 O
hours O
and O
subsequent O
decline O
at O
24 O
hours O
. O

3NT O
levels O
were O
significantly O
increased O
in O
all O
subcellular O
compartments O
at O
6 O
hours O
and O
subsequently O
declined O
at O
24 O
hours O
. O

Our O
data O
showed O
ADR B
induced O
4HNE B
- O
protein O
adducts O
in O
mitochondria O
at O
the O
same O
time O
point O
as O
when O
mitochondrial O
injury O
initially O
appeared O
. O

These O
results O
document O
for O
the O
first O
time O
in O
vivo O
that O
mitochondrial O
oxidative O
damage O
precedes O
nitrative O
damage O
. O

The O
progressive O
nature O
of O
mitochondrial O
injury O
suggests O
that O
mitochondria O
, O
not O
other O
subcellular O
organelles O
, O
are O
the O
major O
site O
of O
intracellular O
injury O
. O

Sotalol B
- O
induced O
coronary O
spasm O
in O
a O
patient O
with O
dilated O
cardiomyopathy O
associated O
with O
sustained O
ventricular O
tachycardia O
. O

A O
54 O
- O
year O
- O
old O
man O
with O
severe O
left O
ventricular O
dysfunction O
due O
to O
dilated O
cardiomyopathy O
was O
referred O
to O
our O
hospital O
for O
symptomatic O
incessant O
sustained O
ventricular O
tachycardia O
( O
VT O
) O
. O

After O
the O
administration O
of O
nifekalant B
hydrochloride I
, O
sustained O
VT O
was O
terminated O
. O

An O
alternate O
class O
III O
agent O
, O
sotalol B
, O
was O
also O
effective O
for O
the O
prevention O
of O
VT O
. O

However O
, O
one O
month O
after O
switching O
over O
nifekalant B
to O
sotalol B
, O
a O
short O
duration O
of O
ST O
elevation O
was O
documented O
in O
ECG O
monitoring O
at O
almost O
the O
same O
time O
for O
three O
consecutive O
days O
. O

ST O
elevation O
with O
chest O
discomfort O
disappeared O
since O
he O
began O
taking O
long O
- O
acting O
diltiazem B
. O

Coronary O
vasospasm O
may O
be O
induced O
by O
the O
non O
- O
selective O
beta O
- O
blocking O
properties O
of O
sotalol B
. O

Effects O
of O
the O
antidepressant B
trazodone B
, O
a O
5 B
- I
HT I
2A O
/ O
2C O
receptor O
antagonist O
, O
on O
dopamine B
- O
dependent O
behaviors O
in O
rats O
. O

RATIONALE O
: O
5 B
- I
Hydroxytryptamine I
, O
via O
stimulation O
of O
5 B
- I
HT I
2C O
receptors O
, O
exerts O
a O
tonic O
inhibitory O
influence O
on O
dopaminergic O
neurotransmission O
, O
whereas O
activation O
of O
5 B
- I
HT I
2A O
receptors O
enhances O
stimulated O
DAergic B
neurotransmission O
. O

The O
antidepressant B
trazodone B
is O
a O
5 B
- I
HT I
2A O
/ O
2C O
receptor O
antagonist O
. O

OBJECTIVES O
: O
To O
evaluate O
the O
effect O
of O
trazodone B
treatment O
on O
behaviors O
dependent O
on O
the O
functional O
status O
of O
the O
nigrostriatal O
DAergic O
system O
. O

METHODS O
: O
The O
effect O
of O
pretreatment O
with O
trazodone B
on O
dexamphetamine B
- O
and O
apomorphine B
- O
induced O
oral O
stereotypies O
, O
on O
catalepsy O
induced O
by O
haloperidol B
and O
apomorphine B
( O
0 O
. O
05 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
, O
on O
ergometrine B
- O
induced O
wet O
dog O
shake O
( O
WDS O
) O
behavior O
and O
fluoxetine B
- O
induced O
penile O
erections O
was O
studied O
in O
rats O
. O

We O
also O
investigated O
whether O
trazodone B
induces O
catalepsy O
in O
rats O
. O

RESULTS O
: O
Trazodone B
at O
2 O
. O
5 O
- O
20 O
mg O
/ O
kg O
i O
. O
p O
. O
did O
not O
induce O
catalepsy O
, O
and O
did O
not O
antagonize O
apomorphine B
( O
1 O
. O
5 O
and O
3 O
mg O
/ O
kg O
) O
stereotypy O
and O
apomorphine B
( O
0 O
. O
05 O
mg O
/ O
kg O
) O
- O
induced O
catalepsy O
. O

However O
, O
pretreatment O
with O
5 O
, O
10 O
and O
20 O
mg O
/ O
kg O
i O
. O
p O
. O
trazodone B
enhanced O
dexamphetamine B
stereotypy O
, O
and O
antagonized O
haloperidol B
catalepsy O
, O
ergometrine B
- O
induced O
WDS O
behavior O
and O
fluoxetine B
- O
induced O
penile O
erections O
. O

Trazodone B
at O
30 O
, O
40 O
and O
50 O
mg O
/ O
kg O
i O
. O
p O
. O
induced O
catalepsy O
and O
antagonized O
apomorphine B
and O
dexamphetamine B
stereotypies O
. O

CONCLUSIONS O
: O
Our O
results O
indicate O
that O
trazodone B
at O
2 O
. O
5 O
- O
20 O
mg O
/ O
kg O
does O
not O
block O
pre O
- O
and O
postsynaptic O
striatal O
D2 O
DA B
receptors O
, O
while O
at O
30 O
, O
40 O
and O
50 O
mg O
/ O
kg O
it O
blocks O
postsynaptic O
striatal O
D2 O
DA B
receptors O
. O

Furthermore O
, O
at O
5 O
, O
10 O
and O
20 O
mg O
/ O
kg O
, O
trazodone B
blocks O
5 B
- I
HT I
2A O
and O
5 B
- I
HT I
2C O
receptors O
. O

We O
suggest O
that O
trazodone B
( O
5 O
, O
10 O
and O
20 O
mg O
/ O
kg O
) O
, O
by O
blocking O
the O
5 B
- I
HT I
2C O
receptors O
, O
releases O
the O
nigrostriatal O
DAergic B
neurons O
from O
tonic O
inhibition O
caused O
by O
5 B
- I
HT I
, O
and O
thereby O
potentiates O
dexamphetamine B
stereotypy O
and O
antagonizes O
haloperidol B
catalepsy O
. O

Swallowing O
abnormalities O
and O
dyskinesia O
in O
Parkinson O
' O
s O
disease O
. O

Gastrointestinal O
abnormalities O
in O
Parkinson O
' O
s O
disease O
( O
PD O
) O
have O
been O
known O
for O
almost O
two O
centuries O
, O
but O
many O
aspects O
concerning O
their O
pathophysiology O
have O
not O
been O
completely O
clarified O
. O

The O
aim O
of O
this O
study O
was O
to O
characterize O
the O
oropharyngeal O
dynamics O
in O
PD O
patients O
with O
and O
without O
levodopa B
- O
induced O
dyskinesia O
. O

Fifteen O
dyskinetic O
, O
12 O
nondyskinetic O
patients O
, O
and O
a O
control O
group O
were O
included O
. O

Patients O
were O
asked O
about O
dysphagia O
and O
evaluated O
with O
the O
Unified O
Parkinson O
' O
s O
Disease O
Rating O
Scale O
Parts O
II O
and O
III O
and O
the O
Hoehn O
and O
Yahr O
scale O
. O

Deglutition O
was O
assessed O
using O
modified O
barium B
swallow O
with O
videofluoroscopy O
. O

Nondyskinetic O
patients O
, O
but O
not O
the O
dyskinetic O
ones O
, O
showed O
less O
oropharyngeal O
swallowing O
efficiency O
( O
OPSE O
) O
for O
liquid O
food O
than O
controls O
( O
Dunnett O
, O
P O
= O
0 O
. O
02 O
) O
. O

Dyskinetic O
patients O
tended O
to O
have O
a O
greater O
OPSE O
than O
nondyskinetic O
( O
Dunnett O
, O
P O
= O
0 O
. O
06 O
) O
. O

Patients O
who O
were O
using O
a O
higher O
dose O
of O
levodopa B
had O
a O
greater O
OPSE O
and O
a O
trend O
toward O
a O
smaller O
oral O
transit O
time O
( O
Pearson O
' O
s O
correlation O
, O
P O
= O
0 O
. O
01 O
and O
0 O
. O
08 O
, O
respectively O
) O
. O

Neither O
the O
report O
of O
dysphagia O
nor O
any O
of O
the O
PD O
severity O
parameters O
correlated O
to O
the O
videofluoroscopic O
variables O
. O

In O
the O
current O
study O
, O
dyskinetic O
patients O
performed O
better O
in O
swallowing O
function O
, O
which O
could O
be O
explained O
on O
the O
basis O
of O
a O
greater O
levodopa B
dose O
. O

Our O
results O
suggest O
a O
role O
for O
levodopa B
in O
the O
oral O
phase O
of O
deglutition O
and O
confirm O
that O
dysphagia O
is O
not O
a O
good O
predictor O
of O
deglutition O
alterations O
in O
PD O
. O

Inhibition O
of O
nuclear O
factor O
- O
kappaB O
activation O
attenuates O
tubulointerstitial O
nephritis O
induced O
by O
gentamicin B
. O

BACKGROUND O
: O
Animals O
treated O
with O
gentamicin B
can O
show O
residual O
areas O
of O
interstitial O
fibrosis O
in O
the O
renal O
cortex O
. O

This O
study O
investigated O
the O
expression O
of O
nuclear O
factor O
- O
kappaB O
( O
NF O
- O
kappaB O
) O
, O
mitogen O
- O
activated O
protein O
( O
MAP O
) O
kinases O
and O
macrophages O
in O
the O
renal O
cortex O
and O
structural O
and O
functional O
renal O
changes O
of O
rats O
treated O
with O
gentamicin B
or O
gentamicin B
+ O
pyrrolidine B
dithiocarbamate I
( O
PDTC B
) O
, O
an O
NF O
- O
kappaB O
inhibitor O
. O

METHODS O
: O
38 O
female O
Wistar O
rats O
were O
injected O
with O
gentamicin B
, O
40 O
mg O
/ O
kg O
, O
twice O
a O
day O
for O
9 O
days O
, O
38 O
with O
gentamicin B
+ O
PDTC B
, O
and O
28 O
with O
0 O
. O
15 O
M O
NaCl B
solution O
. O

The O
animals O
were O
killed O
5 O
and O
30 O
days O
after O
these O
injections O
and O
the O
kidneys O
were O
removed O
for O
histological O
and O
immunohistochemical O
studies O
. O

The O
results O
of O
the O
immunohistochemical O
studies O
were O
scored O
according O
to O
the O
extent O
of O
staining O
. O

The O
fractional O
interstitial O
area O
was O
determined O
by O
morphometry O
. O

RESULTS O
: O
Gentamicin B
- O
treated O
rats O
presented O
a O
transitory O
increase O
in O
plasma O
creatinine B
levels O
. O

Increased O
ED O
- O
1 O
, O
MAP O
kinases O
and O
NF O
- O
kappaB O
staining O
were O
also O
observed O
in O
the O
renal O
cortex O
from O
all O
gentamicin B
- O
treated O
rats O
compared O
to O
control O
( O
p O
< O
0 O
. O
05 O
) O
. O

The O
animals O
killed O
on O
day O
30 O
also O
presented O
fibrosis O
in O
the O
renal O
cortex O
despite O
the O
recovery O
of O
renal O
function O
. O

Treatment O
with O
PDTC B
reduced O
the O
functional O
and O
structural O
changes O
induced O
by O
gentamicin B
. O

CONCLUSIONS O
: O
These O
data O
show O
that O
inhibition O
of O
NF O
- O
kappaB O
activation O
attenuates O
tubulointerstitial O
nephritis O
induced O
by O
gentamicin B
. O

Glucose O
metabolism O
in O
patients O
with O
schizophrenia O
treated O
with O
atypical O
antipsychotic O
agents O
: O
a O
frequently O
sampled O
intravenous O
glucose O
tolerance O
test O
and O
minimal O
model O
analysis O
. O

BACKGROUND O
: O
While O
the O
incidence O
of O
new O
- O
onset O
diabetes O
mellitus O
may O
be O
increasing O
in O
patients O
with O
schizophrenia O
treated O
with O
certain O
atypical O
antipsychotic O
agents O
, O
it O
remains O
unclear O
whether O
atypical O
agents O
are O
directly O
affecting O
glucose O
metabolism O
or O
simply O
increasing O
known O
risk O
factors O
for O
diabetes O
. O

OBJECTIVE O
: O
To O
study O
the O
2 O
drugs O
most O
clearly O
implicated O
( O
clozapine B
and O
olanzapine B
) O
and O
risperidone B
using O
a O
frequently O
sampled O
intravenous O
glucose O
tolerance O
test O
. O

DESIGN O
: O
A O
cross O
- O
sectional O
design O
in O
stable O
, O
treated O
patients O
with O
schizophrenia O
evaluated O
using O
a O
frequently O
sampled O
intravenous O
glucose O
tolerance O
test O
and O
the O
Bergman O
minimal O
model O
analysis O
. O

SETTING O
: O
Subjects O
were O
recruited O
from O
an O
urban O
community O
mental O
health O
clinic O
and O
were O
studied O
at O
a O
general O
clinical O
research O
center O
. O

Patients O
Fifty O
subjects O
signed O
informed O
consent O
and O
41 O
underwent O
the O
frequently O
sampled O
intravenous O
glucose B
tolerance O
test O
. O

Thirty O
- O
six O
nonobese O
subjects O
with O
schizophrenia O
or O
schizoaffective O
disorder O
, O
matched O
by O
body O
mass O
index O
and O
treated O
with O
either O
clozapine B
, O
olanzapine B
, O
or O
risperidone B
, O
were O
included O
in O
the O
analysis O
. O

MAIN O
OUTCOME O
MEASURES O
: O
Fasting O
plasma O
glucose B
and O
fasting O
serum O
insulin O
levels O
, O
insulin O
sensitivity O
index O
, O
homeostasis O
model O
assessment O
of O
insulin O
resistance O
, O
and O
glucose B
effectiveness O
. O

RESULTS O
: O
The O
mean O
+ O
/ O
- O
SD O
duration O
of O
treatment O
with O
the O
identified O
atypical O
antipsychotic O
agent O
was O
68 O
. O
3 O
+ O
/ O
- O
28 O
. O
9 O
months O
( O
clozapine B
) O
, O
29 O
. O
5 O
+ O
/ O
- O
17 O
. O
5 O
months O
( O
olanzapine B
) O
, O
and O
40 O
. O
9 O
+ O
/ O
- O
33 O
. O
7 O
( O
risperidone B
) O
. O

Fasting O
serum O
insulin O
concentrations O
differed O
among O
groups O
( O
F O
( O
33 O
) O
= O
3 O
. O
35 O
; O
P O
= O
. O
047 O
) O
( O
clozapine B
> O
olanzapine B
> O
risperidone B
) O
with O
significant O
differences O
between O
clozapine B
and O
risperidone B
( O
t O
( O
33 O
) O
= O
2 O
. O
32 O
; O
P O
= O
. O
03 O
) O
and O
olanzapine B
and O
risperidone B
( O
t O
( O
33 O
) O
= O
2 O
. O
15 O
; O
P O
= O
. O
04 O
) O
. O

There O
was O
a O
significant O
difference O
in O
insulin O
sensitivity O
index O
among O
groups O
( O
F O
( O
33 O
) O
= O
10 O
. O
66 O
; O
P O
< O
. O
001 O
) O
( O
clozapine B
< O
olanzapine B
< O
risperidone B
) O
, O
with O
subjects O
who O
received O
clozapine B
and O
olanzapine B
exhibiting O
significant O
insulin O
resistance O
compared O
with O
subjects O
who O
were O
treated O
with O
risperidone B
( O
clozapine B
vs O
risperidone B
, O
t O
( O
33 O
) O
= O
- O
4 O
. O
29 O
; O
P O
< O
. O
001 O
; O
olanzapine B
vs O
risperidone B
, O
t O
( O
33 O
) O
= O
- O
3 O
. O
62 O
; O
P O
= O
. O

001 O
[ O
P O
< O
. O
001 O
] O
) O
. O

The O
homeostasis O
model O
assessment O
of O
insulin O
resistance O
also O
differed O
significantly O
among O
groups O
( O
F O
( O
33 O
) O
= O
4 O
. O
92 O
; O
P O
= O
. O
01 O
) O
( O
clozapine B
> O
olanzapine B
> O
risperidone B
) O
( O
clozapine B
vs O
risperidone B
, O
t O
( O
33 O
) O
= O
2 O
. O
94 O
; O
P O
= O
. O
006 O
; O
olanzapine B
vs O
risperidone B
, O
t O
( O
33 O
) O
= O
2 O
. O
42 O
; O
P O
= O
. O
02 O
) O
. O

There O
was O
a O
significant O
difference O
among O
groups O
in O
glucose B
effectiveness O
( O
F O
( O
30 O
) O
= O
4 O
. O
18 O
; O
P O
= O
. O
02 O
) O
( O
clozapine B
< O
olanzapine B
< O
risperidone B
) O
with O
significant O
differences O
between O
clozapine B
and O
risperidone B
( O
t O
( O
30 O
) O
= O
- O
2 O
. O
59 O
; O
P O
= O
. O
02 O
) O
and O
olanzapine B
and O
risperidone B
( O
t O
( O
30 O
) O
= O
- O
2 O
. O
34 O
, O
P O
= O
. O
03 O
) O
. O

CONCLUSIONS O
: O
Both O
nonobese O
clozapine B
- O
and O
olanzapine B
- O
treated O
groups O
displayed O
significant O
insulin O
resistance O
and O
impairment O
of O
glucose O
effectiveness O
compared O
with O
risperidone B
- O
treated O
subjects O
. O

Patients O
taking O
clozapine B
and O
olanzapine B
must O
be O
examined O
for O
insulin O
resistance O
and O
its O
consequences O
. O

Thoracic O
hematomyelia O
secondary O
to O
coumadin B
anticoagulant O
therapy O
: O
a O
case O
report O
. O

A O
case O
of O
thoracic O
hematomyelia O
secondary O
to O
anticoagulant O
therapy O
is O
presented O
. O

Clinical O
features O
, O
similar O
to O
2 O
other O
previously O
reported O
cases O
, O
are O
discussed O
. O

A O
high O
index O
of O
suspicion O
may O
lead O
to O
a O
quick O
diagnostic O
procedure O
and O
successful O
decompressive O
surgery O
. O

Mania O
associated O
with O
fluoxetine B
treatment O
in O
adolescents O
. O

Fluoxetine B
, O
a O
selective O
serotonin B
reuptake O
inhibitor O
, O
is O
gaining O
increased O
acceptance O
in O
the O
treatment O
of O
adolescent O
depression O
. O

Generally O
safe O
and O
well O
tolerated O
by O
adults O
, O
fluoxetine B
has O
been O
reported O
to O
induce O
mania O
. O

The O
cases O
of O
five O
depressed O
adolescents O
, O
14 O
- O
16 O
years O
of O
age O
, O
who O
developed O
mania O
during O
pharmacotherapy O
with O
fluoxetine B
, O
are O
reported O
here O
. O

Apparent O
risk O
factors O
for O
the O
development O
of O
mania O
or O
hypomania O
during O
fluoxetine B
pharmacotherapy O
in O
this O
population O
were O
the O
combination O
of O
attention O
- O
deficit O
hyperactivity O
disorder O
and O
affective O
instability O
; O
major O
depression O
with O
psychotic O
features O
; O
a O
family O
history O
of O
affective O
disorder O
, O
especially O
bipolar O
disorder O
; O
and O
a O
diagnosis O
of O
bipolar O
disorder O
. O

Further O
study O
is O
needed O
to O
determine O
the O
optimal O
dosage O
and O
to O
identify O
risk O
factors O
that O
increase O
individual O
vulnerability O
to O
fluoxetine B
induced O
mania O
in O
adolescents O
. O

Acute O
renal O
insufficiency O
after O
high O
- O
dose O
melphalan B
in O
patients O
with O
primary O
systemic O
amyloidosis O
during O
stem O
cell O
transplantation O
. O

BACKGROUND O
: O
Patients O
with O
primary O
systemic O
amyloidosis O
( O
AL O
) O
have O
a O
poor O
prognosis O
. O

Median O
survival O
time O
from O
standard O
treatments O
is O
only O
17 O
months O
. O

High O
- O
dose O
intravenous O
melphalan B
followed O
by O
peripheral O
blood O
stem O
cell O
transplant O
( O
PBSCT O
) O
appears O
to O
be O
the O
most O
promising O
therapy O
, O
but O
treatment O
mortality O
can O
be O
high O
. O

The O
authors O
have O
noted O
the O
development O
of O
acute O
renal O
insufficiency O
immediately O
after O
melphalan B
conditioning O
. O

This O
study O
was O
undertaken O
to O
further O
examine O
its O
risk O
factors O
and O
impact O
on O
posttransplant O
mortality O
. O

METHODS O
: O
Consecutive O
AL O
patients O
who O
underwent O
PBSCT O
were O
studied O
retrospectively O
. O

Acute O
renal O
insufficiency O
( O
ARI O
) O
after O
high O
- O
dose O
melphalan B
was O
defined O
by O
a O
minimum O
increase O
of O
0 O
. O
5 O
mg O
/ O
dL O
( O
44 O
micromol O
/ O
L O
) O
in O
the O
serum O
creatinine B
level O
that O
is O
greater O
than O
50 O
% O
of O
baseline O
immediately O
after O
conditioning O
. O

Urine O
sediment O
score O
was O
the O
sum O
of O
the O
individual O
types O
of O
sediment O
identified O
on O
urine O
microscopy O
. O

RESULTS O
: O
Of O
the O
80 O
patients O
studied O
, O
ARI O
developed O
in O
18 O
. O
8 O
% O
of O
the O
patients O
after O
high O
- O
dose O
melphalan B
. O

Univariate O
analysis O
identified O
age O
, O
hypoalbuminemia O
, O
heavy O
proteinuria O
, O
diuretic B
use O
, O
and O
urine O
sediment O
score O
( O
> O
3 O
) O
as O
risk O
factors O
. O

Age O
and O
urine O
sediment O
score O
remained O
independently O
significant O
risk O
factors O
in O
the O
multivariate O
analysis O
. O

Patients O
who O
had O
ARI O
after O
high O
- O
dose O
melphalan B
underwent O
dialysis O
more O
often O
( O
P O
= O
0 O
. O
007 O
) O
, O
and O
had O
a O
worse O
1 O
- O
year O
survival O
( O
P O
= O
0 O
. O
03 O
) O
. O

CONCLUSION O
: O
The O
timing O
of O
renal O
injury O
strongly O
suggests O
melphalan B
as O
the O
causative O
agent O
. O

Ongoing O
tubular O
injury O
may O
be O
a O
prerequisite O
for O
renal O
injury O
by O
melphalan B
as O
evidenced O
by O
the O
active O
urinary O
sediment O
. O

Development O
of O
ARI O
adversely O
affected O
the O
outcome O
after O
PBSCT O
. O

Effective O
preventive O
measures O
may O
help O
decrease O
the O
treatment O
mortality O
of O
PBSCT O
in O
AL O
patients O
. O

Focal O
cerebral O
ischemia O
in O
rats O
: O
effect O
of O
phenylephrine B
- O
induced O
hypertension O
during O
reperfusion O
. O

After O
180 O
min O
of O
temporary O
middle O
cerebral O
artery O
occlusion O
in O
spontaneously O
hypertensive O
rats O
, O
the O
effect O
of O
phenylephrine B
- O
induced O
hypertension O
on O
ischemic O
brain O
injury O
and O
blood O
- O
brain O
barrier O
permeability O
was O
determined O
. O

Blood O
pressure O
was O
manipulated O
by O
one O
of O
the O
following O
schedules O
during O
120 O
min O
of O
reperfusion O
: O
Control O
, O
normotensive O
reperfusion O
; O
90 O
/ O
hypertension O
( O
90 O
/ O
HTN O
) O
, O
blood O
pressure O
was O
increased O
by O
35 O
mm O
Hg O
during O
the O
initial O
90 O
min O
of O
reperfusion O
only O
; O
15 O
/ O
hypertension O
( O
15 O
/ O
HTN O
) O
, O
normotensive O
reperfusion O
for O
30 O
min O
followed O
by O
15 O
min O
of O
hypertension O
and O
75 O
min O
of O
normotension O
. O

Part O
A O
, O
for O
eight O
rats O
in O
each O
group O
brain O
injury O
was O
evaluated O
by O
staining O
tissue O
using O
2 B
, I
3 I
, I
5 I
- I
triphenyltetrazolium I
chloride I
and O
edema O
was O
evaluated O
by O
microgravimetry O
. O

Part O
B O
, O
for O
eight O
different O
rats O
in O
each O
group O
blood O
- O
brain O
barrier O
permeability O
was O
evaluated O
by O
measuring O
the O
amount O
and O
extent O
of O
extravasation O
of O
Evans B
Blue I
dye O
. O

Brain O
injury O
( O
percentage O
of O
the O
ischemic O
hemisphere O
) O
was O
less O
in O
the O
15 O
/ O
HTN O
group O
( O
16 O
+ O
/ O
- O
6 O
, O
mean O
+ O
/ O
- O
SD O
) O
versus O
the O
90 O
/ O
HTN O
group O
( O
30 O
+ O
/ O
- O
6 O
) O
, O
which O
was O
in O
turn O
less O
than O
the O
control O
group O
( O
42 O
+ O
/ O
- O
5 O
) O
. O

Specific O
gravity O
was O
greater O
in O
the O
15 O
/ O
HTN O
group O
( O
1 O
. O
043 O
+ O
/ O
- O
0 O
. O
002 O
) O
versus O
the O
90 O
/ O
HTN O
( O
1 O
. O
036 O
+ O
/ O
- O
0 O
. O
003 O
) O
and O
control O
( O
1 O
. O
037 O
+ O
/ O
- O
0 O
. O
003 O
) O
groups O
. O

Evans B
Blue I
( O
mug O
g O
- O
1 O
of O
brain O
tissue O
) O
was O
greater O
in O
the O
90 O
/ O
HTN O
group O
( O
24 O
. O
4 O
+ O
/ O
- O
6 O
. O
0 O
) O
versus O
the O
control O
group O
( O
12 O
. O
3 O
+ O
/ O
- O
4 O
. O
1 O
) O
, O
which O
was O
in O
turn O
greater O
than O
the O
15 O
/ O
HTN O
group O
( O
7 O
. O
3 O
+ O
/ O
- O
3 O
. O
2 O
) O
. O

This O
study O
supports O
a O
hypothesis O
that O
during O
reperfusion O
, O
a O
short O
interval O
of O
hypertension O
decreases O
brain O
injury O
and O
edema O
; O
and O
that O
sustained O
hypertension O
increases O
the O
risk O
of O
vasogenic O
edema O
. O

People O
aged O
over O
75 O
in O
atrial O
fibrillation O
on O
warfarin B
: O
the O
rate O
of O
major O
hemorrhage O
and O
stroke O
in O
more O
than O
500 O
patient O
- O
years O
of O
follow O
- O
up O
. O

OBJECTIVES O
: O
To O
determine O
the O
incidence O
of O
major O
hemorrhage O
and O
stroke O
in O
people O
aged O
76 O
and O
older O
with O
atrial O
fibrillation O
on O
adjusted O
- O
dose O
warfarin B
who O
had O
been O
recently O
been O
admitted O
to O
hospital O
. O

DESIGN O
: O
A O
retrospective O
observational O
cohort O
study O
. O

SETTING O
: O
A O
major O
healthcare O
network O
involving O
four O
tertiary O
hospitals O
. O

PARTICIPANTS O
: O
Two O
hundred O
thirty O
- O
five O
patients O
aged O
76 O
and O
older O
admitted O
to O
a O
major O
healthcare O
network O
between O
July O
1 O
, O
2001 O
, O
and O
June O
30 O
, O
2002 O
, O
with O
atrial O
fibrillation O
on O
warfarin B
were O
enrolled O
. O

MEASUREMENTS O
: O
Information O
regarding O
major O
bleeding O
episodes O
, O
strokes O
, O
and O
warfarin B
use O
was O
obtained O
from O
patients O
, O
relatives O
, O
primary O
physicians O
, O
and O
medical O
records O
. O

RESULTS O
: O
Two O
hundred O
twenty O
- O
eight O
patients O
( O
42 O
% O
men O
) O
with O
a O
mean O
age O
of O
81 O
. O
1 O
( O
range O
76 O
- O
94 O
) O
were O
included O
in O
the O
analysis O
. O

Total O
follow O
- O
up O
on O
warfarin B
was O
530 O
years O
( O
mean O
28 O
months O
) O
. O

There O
were O
53 O
major O
hemorrhages O
, O
for O
an O
annual O
rate O
of O
10 O
. O
0 O
% O
, O
including O
24 O
( O
45 O
. O
3 O
% O
) O
life O
- O
threatening O
and O
five O
( O
9 O
. O
4 O
% O
) O
fatal O
bleeds O
. O

The O
annual O
stroke O
rate O
after O
initiation O
of O
warfarin B
was O
2 O
. O
6 O
% O
. O

CONCLUSION O
: O
The O
rate O
of O
major O
hemorrhage O
was O
high O
in O
this O
old O
, O
frail O
group O
, O
but O
excluding O
fatalities O
, O
resulted O
in O
no O
long O
- O
term O
sequelae O
, O
and O
the O
stroke O
rate O
on O
warfarin B
was O
low O
, O
demonstrating O
how O
effective O
warfarin B
treatment O
is O
. O

Safety O
of O
celecoxib B
in O
patients O
with O
adverse O
skin O
reactions O
to O
acetaminophen B
( O
paracetamol B
) O
and O
nimesulide B
associated O
or O
not O
with O
common O
non O
- O
steroidal O
anti O
- O
inflammatory O
drugs O
. O

BACKGROUND O
: O
Acetaminophen B
( O
paracetamol B
- O
- O
P B
) O
and O
Nimesulide B
( O
N B
) O
are O
widely O
used O
analgesic O
- O
antipyretic O
/ O
anti O
- O
inflammatory O
drugs O
. O

The O
rate O
of O
adverse O
hypersensitivity O
reactions O
to O
these O
agents O
is O
generally O
low O
. O

On O
the O
contrary O
non O
- O
steroidal O
anti O
- O
inflammatory O
drugs O
( O
NSAIDs O
) O
are O
commonly O
involved O
in O
such O
reactions O
. O

Celecoxib B
( O
CE O
) O
is O
a O
novel O
drug O
, O
with O
high O
selectivity O
and O
affinity O
for O
COX O
- O
2 O
enzyme O
. O

OBJECTIVE O
: O
We O
evaluated O
the O
tolerability O
of O
CE O
in O
a O
group O
of O
patients O
with O
documented O
history O
of O
adverse O
cutaneous O
reactions O
to O
P B
and O
N B
associated O
or O
not O
to O
classic O
NSAIDs O
. O

METHODS O
: O
We O
studied O
9 O
patients O
with O
hypersensitivity O
to O
P B
and O
N B
with O
or O
without O
associated O
reactions O
to O
classic O
NSAIDs O
. O

The O
diagnosis O
of O
P B
and O
N B
- O
induced O
skin O
reactions O
was O
based O
in O
vivo O
challenge O
. O

The O
placebo O
was O
blindly O
administered O
at O
the O
beginning O
of O
each O
challenge O
. O

After O
three O
days O
, O
a O
cumulative O
dosage O
of O
200 O
mg O
of O
CE B
in O
refracted O
doses O
were O
given O
. O

After O
2 O
- O
3 O
days O
, O
a O
single O
dose O
of O
200 O
mg O
was O
administered O
. O

All O
patients O
were O
observed O
for O
6 O
hours O
after O
each O
challenge O
, O
and O
controlled O
again O
after O
24 O
hours O
to O
exclude O
delayed O
reactions O
. O

The O
challenge O
was O
considered O
positive O
if O
one O
or O
more O
of O
the O
following O
appeared O
: O
erythema O
, O
rush O
or O
urticaria O
- O
angioedema O
. O

RESULTS O
: O
No O
reaction O
was O
observed O
with O
placebo O
and O
eight O
patients O
( O
88 O
. O
8 O
% O
) O
tolerated O
CE O
. O

Only O
one O
patient O
developed O
a O
moderate O
angioedema O
of O
the O
lips O
. O

CONCLUSION O
: O
Only O
one O
hypersensitivity O
reaction O
to O
CE B
was O
documented O
among O
9 O
P O
and O
N B
- O
highly O
NSAIDs O
intolerant O
patients O
. O

Thus O
, O
we O
conclude O
that O
CE B
is O
a O
reasonably O
safe O
alternative O
to O
be O
used O
in O
subjects O
who O
do O
not O
tolerate O
P B
and O
N B
. O

Case O
- O
control O
study O
of O
regular O
analgesic O
and O
nonsteroidal O
anti O
- O
inflammatory O
use O
and O
end O
- O
stage O
renal O
disease O
. O

BACKGROUND O
: O
Studies O
on O
the O
association O
between O
the O
long O
- O
term O
use O
of O
aspirin B
and O
other O
analgesic O
and O
nonsteroidal O
anti O
- O
inflammatory O
drugs O
( O
NSAIDs O
) O
and O
end O
- O
stage O
renal O
disease O
( O
ESRD O
) O
have O
given O
conflicting O
results O
. O

In O
order O
to O
examine O
this O
association O
, O
a O
case O
- O
control O
study O
with O
incident O
cases O
of O
ESRD O
was O
carried O
out O
. O

METHODS O
: O
The O
cases O
were O
all O
patients O
entering O
the O
local O
dialysis O
program O
because O
of O
ESRD O
in O
the O
study O
area O
between O
June O
1 O
, O
1995 O
and O
November O
30 O
, O
1997 O
. O

They O
were O
classified O
according O
to O
the O
underlying O
disease O
, O
which O
had O
presumably O
led O
them O
to O
ESRD O
. O

Controls O
were O
patients O
admitted O
to O
the O
same O
hospitals O
from O
where O
the O
cases O
arose O
, O
also O
matched O
by O
age O
and O
sex O
. O

Odds O
ratios O
were O
calculated O
using O
a O
conditional O
logistic O
model O
, O
including O
potential O
confounding O
factors O
, O
both O
for O
the O
whole O
study O
population O
and O
for O
the O
various O
underlying O
diseases O
. O

RESULTS O
: O
Five O
hundred O
and O
eighty O
- O
three O
cases O
and O
1190 O
controls O
were O
included O
in O
the O
analysis O
. O

Long O
- O
term O
use O
of O
any O
analgesic O
was O
associated O
with O
an O
overall O
odds O
ratio O
of O
1 O
. O
22 O
( O
95 O
% O
CI O
, O
0 O
. O
89 O
- O
1 O
. O
66 O
) O
. O

For O
specific O
groups O
of O
drugs O
, O
the O
risks O
were O
1 O
. O
56 O
( O
1 O
. O
05 O
- O
2 O
. O
30 O
) O
for O
aspirin B
, O
1 O
. O
03 O
( O
0 O
. O
60 O
- O
1 O
. O
76 O
) O
for O
pyrazolones B
, O
0 O
. O
80 O
( O
0 O
. O
39 O
- O
1 O
. O
63 O
) O
for O
paracetamol B
, O
and O
0 O
. O
94 O
( O
0 O
. O
57 O
- O
1 O
. O
56 O
) O
for O
nonaspirin O
NSAIDs O
. O

The O
risk O
of O
ESRD O
associated O
with O
aspirin B
was O
related O
to O
the O
cumulated O
dose O
and O
duration O
of O
use O
, O
and O
it O
was O
particularly O
high O
among O
the O
subset O
of O
patients O
with O
vascular O
nephropathy O
as O
underlying O
disease O
[ O
2 O
. O
35 O
( O
1 O
. O
17 O
- O
4 O
. O
72 O
) O
] O
. O

CONCLUSION O
: O
Our O
data O
indicate O
that O
long O
- O
term O
use O
of O
nonaspirin O
analgesic O
drugs O
and O
NSAIDs O
is O
not O
associated O
with O
an O
increased O
risk O
of O
ESRD O
. O

However O
, O
the O
chronic O
use O
of O
aspirin B
may O
increase O
the O
risk O
of O
ESRD O
. O

Two O
cases O
of O
amisulpride B
overdose O
: O
a O
cause O
for O
prolonged O
QT O
syndrome O
. O

Two O
cases O
of O
deliberate O
self O
- O
poisoning O
with O
5 O
g O
and O
3 O
. O
6 O
g O
of O
amisulpride B
, O
respectively O
, O
are O
reported O
. O

In O
both O
cases O
, O
QT O
prolongation O
and O
hypocalcaemia O
were O
noted O
. O

The O
QT O
prolongation O
appeared O
to O
respond O
to O
administration O
of O
i O
. O
v O
. O
calcium B
gluconate I
. O

Growth O
- O
associated O
protein O
43 O
expression O
in O
hippocampal O
molecular O
layer O
of O
chronic O
epileptic O
rats O
treated O
with O
cycloheximide B
. O

PURPOSE O
: O
GAP43 O
has O
been O
thought O
to O
be O
linked O
with O
mossy O
fiber O
sprouting O
( O
MFS O
) O
in O
various O
experimental O
models O
of O
epilepsy O
. O

To O
investigate O
how O
GAP43 O
expression O
( O
GAP43 O
- O
ir O
) O
correlates O
with O
MFS O
, O
we O
assessed O
the O
intensity O
( O
densitometry O
) O
and O
extension O
( O
width O
) O
of O
GAP43 O
- O
ir O
in O
the O
inner O
molecular O
layer O
of O
the O
dentate O
gyrus O
( O
IML O
) O
of O
rats O
subject O
to O
status O
epilepticus O
induced O
by O
pilocarpine B
( O
Pilo B
) O
, O
previously O
injected O
or O
not O
with O
cycloheximide B
( O
CHX B
) O
, O
which O
has O
been O
shown O
to O
inhibit O
MFS O
. O

METHODS O
: O
CHX B
was O
injected O
before O
the O
Pilo B
injection O
in O
adult O
Wistar O
rats O
. O

The O
Pilo B
group O
was O
injected O
with O
the O
same O
drugs O
, O
except O
for O
CHX B
. O

Animals O
were O
killed O
between O
30 O
and O
60 O
days O
later O
, O
and O
brain O
sections O
were O
processed O
for O
GAP43 O
immunohistochemistry O
. O

RESULTS O
: O
Densitometry O
showed O
no O
significant O
difference O
regarding O
GAP43 O
- O
ir O
in O
the O
IML O
between O
Pilo B
, O
CHX B
+ O
Pilo B
, O
and O
control O
groups O
. O

However O
, O
the O
results O
of O
the O
width O
of O
the O
GAP43 O
- O
ir O
band O
in O
the O
IML O
showed O
that O
CHX B
+ O
Pilo B
and O
control O
animals O
had O
a O
significantly O
larger O
band O
( O
p O
= O
0 O
. O
03 O
) O
as O
compared O
with O
that O
in O
the O
Pilo B
group O
. O

CONCLUSIONS O
: O
Our O
current O
finding O
that O
animals O
in O
the O
CHX B
+ O
Pilo B
group O
have O
a O
GAP43 O
- O
ir O
band O
in O
the O
IML O
, O
similar O
to O
that O
of O
controls O
, O
reinforces O
prior O
data O
on O
the O
blockade O
of O
MFS O
in O
these O
animals O
. O

The O
change O
in O
GAP43 O
- O
ir O
present O
in O
Pilo B
- O
treated O
animals O
was O
a O
thinning O
of O
the O
band O
to O
a O
very O
narrow O
layer O
just O
above O
the O
granule O
cell O
layer O
that O
is O
likely O
to O
be O
associated O
with O
the O
loss O
of O
hilar O
cell O
projections O
that O
express O
GAP O
- O
43 O
. O

Nicotine B
antagonizes O
caffeine B
- O
but O
not O
pentylenetetrazole B
- O
induced O
anxiogenic O
effect O
in O
mice O
. O

RATIONALE O
: O
Nicotine B
and O
caffeine B
are O
widely O
consumed O
licit O
psychoactive O
drugs O
worldwide O
. O

Epidemiological O
studies O
showed O
that O
they O
were O
generally O
used O
concurrently O
. O

Although O
some O
studies O
in O
experimental O
animals O
indicate O
clear O
pharmacological O
interactions O
between O
them O
, O
no O
studies O
have O
shown O
a O
specific O
interaction O
on O
anxiety O
responses O
. O

OBJECTIVES O
: O
The O
present O
study O
investigates O
the O
effects O
of O
nicotine B
on O
anxiety O
induced O
by O
caffeine B
and O
another O
anxiogenic O
drug O
, O
pentylenetetrazole B
, O
in O
mice O
. O

The O
elevated O
plus O
- O
maze O
( O
EPM O
) O
test O
was O
used O
to O
evaluate O
the O
effects O
of O
drugs O
on O
anxiety O
. O

METHODS O
: O
Adult O
male O
Swiss O
Webster O
mice O
( O
25 O
- O
32 O
g O
) O
were O
given O
nicotine B
( O
0 O
. O
05 O
- O
0 O
. O
25 O
mg O
/ O
kg O
s O
. O
c O
. O
) O
or O
saline O
10 O
min O
before O
caffeine B
( O
70 O
mg O
/ O
kg O
i O
. O
p O
. O
) O
or O
pentylenetetrazole B
( O
15 O
and O
30 O
mg O
/ O
kg O
i O
. O
p O
. O
) O
injections O
. O

After O
15 O
min O
, O
mice O
were O
evaluated O
for O
their O
open O
- O
and O
closed O
- O
arm O
time O
and O
entries O
on O
the O
EPM O
for O
a O
10 O
- O
min O
session O
. O

Locomotor O
activity O
was O
recorded O
for O
individual O
groups O
by O
using O
the O
same O
treatment O
protocol O
with O
the O
EPM O
test O
. O

RESULTS O
: O
Nicotine B
( O
0 O
. O
05 O
- O
0 O
. O
25 O
mg O
/ O
kg O
) O
itself O
did O
not O
produce O
any O
significant O
effect O
in O
the O
EPM O
test O
, O
whereas O
caffeine B
( O
70 O
mg O
/ O
kg O
) O
and O
pentylenetetrazole B
( O
30 O
mg O
/ O
kg O
) O
produced O
an O
anxiogenic O
effect O
, O
apparent O
with O
decreases O
in O
open O
- O
arm O
time O
and O
entry O
. O

Nicotine B
( O
0 O
. O
25 O
mg O
/ O
kg O
) O
pretreatment O
blocked O
the O
caffeine B
- O
but O
not O
pentylenetetrazole B
- O
induced O
anxiety O
. O

Administration O
of O
each O
drug O
and O
their O
combinations O
did O
not O
produce O
any O
effect O
on O
locomotor O
activity O
. O

CONCLUSIONS O
: O
Our O
results O
suggest O
that O
the O
antagonistic O
effect O
of O
nicotine B
on O
caffeine B
- O
induced O
anxiety O
is O
specific O
to O
caffeine B
, O
instead O
of O
a O
non O
- O
specific O
anxiolytic O
effect O
. O

Thus O
, O
it O
may O
extend O
the O
current O
findings O
on O
the O
interaction O
between O
nicotine B
and O
caffeine B
. O

Long O
term O
hormone O
therapy O
for O
perimenopausal O
and O
postmenopausal O
women O
. O

BACKGROUND O
: O
Hormone O
therapy O
( O
HT O
) O
is O
widely O
used O
for O
controlling O
menopausal O
symptoms O
. O

It O
has O
also O
been O
used O
for O
the O
management O
and O
prevention O
of O
cardiovascular O
disease O
, O
osteoporosis O
and O
dementia O
in O
older O
women O
but O
the O
evidence O
supporting O
its O
use O
for O
these O
indications O
is O
largely O
observational O
. O

OBJECTIVES O
: O
To O
assess O
the O
effect O
of O
long O
- O
term O
HT O
on O
mortality O
, O
heart O
disease O
, O
venous O
thromboembolism O
, O
stroke O
, O
transient O
ischaemic O
attacks O
, O
breast O
cancer O
, O
colorectal O
cancer O
, O
ovarian O
cancer O
, O
endometrial O
cancer O
, O
gallbladder O
disease O
, O
cognitive O
function O
, O
dementia O
, O
fractures O
and O
quality O
of O
life O
. O

SEARCH O
STRATEGY O
: O
We O
searched O
the O
following O
databases O
up O
to O
November O
2004 O
: O
the O
Cochrane O
Menstrual O
Disorders O
and O
Subfertility O
Group O
Trials O
Register O
, O
Cochrane O
Central O
Register O
of O
Controlled O
Trials O
( O
CENTRAL O
) O
, O
MEDLINE O
, O
EMBASE O
, O
Biological O
Abstracts O
. O

Relevant O
non O
- O
indexed O
journals O
and O
conference O
abstracts O
were O
also O
searched O
. O

SELECTION O
CRITERIA O
: O
Randomised O
double O
- O
blind O
trials O
of O
HT O
( O
oestrogens B
with O
or O
without O
progestogens B
) O
versus O
placebo O
, O
taken O
for O
at O
least O
one O
year O
by O
perimenopausal O
or O
postmenopausal O
women O
. O

DATA O
COLLECTION O
AND O
ANALYSIS O
: O
Fifteen O
RCTs O
were O
included O
. O

Trials O
were O
assessed O
for O
quality O
and O
two O
review O
authors O
extracted O
data O
independently O
. O

They O
calculated O
risk O
ratios O
for O
dichotomous O
outcomes O
and O
weighted O
mean O
differences O
for O
continuous O
outcomes O
. O

Clinical O
heterogeneity O
precluded O
meta O
- O
analysis O
for O
most O
outcomes O
. O

MAIN O
RESULTS O
: O
All O
the O
statistically O
significant O
results O
were O
derived O
from O
the O
two O
biggest O
trials O
. O

In O
relatively O
healthy O
women O
, O
combined O
continuous O
HT O
significantly O
increased O
the O
risk O
of O
venous O
thromboembolism O
or O
coronary O
event O
( O
after O
one O
year O
' O
s O
use O
) O
, O
stroke O
( O
after O
3 O
years O
) O
, O
breast O
cancer O
( O
after O
5 O
years O
) O
and O
gallbladder O
disease O
. O

Long O
- O
term O
oestrogen B
- O
only O
HT O
also O
significantly O
increased O
the O
risk O
of O
stroke O
and O
gallbladder O
disease O
. O

Overall O
, O
the O
only O
statistically O
significant O
benefits O
of O
HT O
were O
a O
decreased O
incidence O
of O
fractures O
and O
colon O
cancer O
with O
long O
- O
term O
use O
. O

Among O
relatively O
healthy O
women O
over O
65 O
years O
taking O
continuous O
combined O
HT O
, O
there O
was O
a O
statistically O
significant O
increase O
in O
the O
incidence O
of O
dementia O
. O

Among O
women O
with O
cardiovascular O
disease O
, O
long O
- O
term O
use O
of O
combined O
continuous O
HT O
significantly O
increased O
the O
risk O
of O
venous O
thromboembolism O
. O

No O
trials O
focussed O
specifically O
on O
younger O
women O
. O

However O
, O
one O
trial O
analysed O
subgroups O
of O
2839 O
relatively O
healthy O
50 O
to O
59 O
year O
- O
old O
women O
taking O
combined O
continuous O
HT O
and O
1637 O
taking O
oestrogen B
- O
only O
HT O
, O
versus O
similar O
- O
sized O
placebo O
groups O
. O

The O
only O
significantly O
increased O
risk O
reported O
was O
for O
venous O
thromboembolism O
in O
women O
taking O
combined O
continuous O
HT O
; O
their O
absolute O
risk O
remained O
very O
low O
. O

AUTHORS O
' O
CONCLUSIONS O
: O
HT O
is O
not O
indicated O
for O
the O
routine O
management O
of O
chronic O
disease O
. O

We O
need O
more O
evidence O
on O
the O
safety O
of O
HT O
for O
menopausal O
symptom O
control O
, O
though O
short O
- O
term O
use O
appears O
to O
be O
relatively O
safe O
for O
healthy O
younger O
women O
. O

Drug O
- O
induced O
liver O
injury O
: O
an O
analysis O
of O
461 O
incidences O
submitted O
to O
the O
Spanish O
registry O
over O
a O
10 O
- O
year O
period O
. O

BACKGROUND O
& O
AIMS O
: O
Progress O
in O
the O
understanding O
of O
susceptibility O
factors O
to O
drug O
- O
induced O
liver O
injury O
( O
DILI O
) O
and O
outcome O
predictability O
are O
hampered O
by O
the O
lack O
of O
systematic O
programs O
to O
detect O
bona O
fide O
cases O
. O

METHODS O
: O
A O
cooperative O
network O
was O
created O
in O
1994 O
in O
Spain O
to O
identify O
all O
suspicions O
of O
DILI O
following O
a O
prospective O
structured O
report O
form O
. O

The O
liver O
damage O
was O
characterized O
according O
to O
hepatocellular O
, O
cholestatic O
, O
and O
mixed O
laboratory O
criteria O
and O
to O
histologic O
criteria O
when O
available O
. O

Further O
evaluation O
of O
causality O
assessment O
was O
centrally O
performed O
. O

RESULTS O
: O
Since O
April O
1994 O
to O
August O
2004 O
, O
461 O
out O
of O
570 O
submitted O
cases O
, O
involving O
505 O
drugs O
, O
were O
deemed O
to O
be O
related O
to O
DILI O
. O

The O
antiinfective O
group O
of O
drugs O
was O
the O
more O
frequently O
incriminated O
, O
amoxicillin B
- I
clavulanate I
accounting O
for O
the O
12 O
. O
8 O
% O
of O
the O
whole O
series O
. O

The O
hepatocellular O
pattern O
of O
damage O
was O
the O
most O
common O
( O
58 O
% O
) O
, O
was O
inversely O
correlated O
with O
age O
( O
P O
< O
. O
0001 O
) O
, O
and O
had O
the O
worst O
outcome O
( O
Cox O
regression O
, O
P O
< O
. O
034 O
) O
. O

Indeed O
, O
the O
incidence O
of O
liver O
transplantation O
and O
death O
in O
this O
group O
was O
11 O
. O
7 O
% O
if O
patients O
had O
jaundice O
at O
presentation O
, O
whereas O
the O
corresponding O
figure O
was O
3 O
. O
8 O
% O
in O
nonjaundiced O
patients O
( O
P O
< O
. O
04 O
) O
. O

Factors O
associated O
with O
the O
development O
of O
fulminant O
hepatic O
failure O
were O
female O
sex O
( O
OR O
= O
25 O
; O
95 O
% O
CI O
: O
4 O
. O
1 O
- O
151 O
; O
P O
< O
. O
0001 O
) O
, O
hepatocellular O
damage O
( O
OR O
= O
7 O
. O
9 O
; O
95 O
% O
CI O
: O
1 O
. O
6 O
- O
37 O
; O
P O
< O
. O
009 O
) O
, O
and O
higher O
baseline O
plasma O
bilirubin B
value O
( O
OR O
= O
1 O
. O
15 O
; O
95 O
% O
CI O
: O
1 O
. O
09 O
- O
1 O
. O
22 O
; O
P O
< O
. O
0001 O
) O
. O

CONCLUSIONS O
: O
Patients O
with O
drug O
- O
induced O
hepatocellular O
jaundice O
have O
11 O
. O
7 O
% O
chance O
of O
progressing O
to O
death O
or O
transplantation O
. O

Amoxicillin B
- I
clavulanate I
stands O
out O
as O
the O
most O
common O
drug O
related O
to O
DILI O
. O

Morphological O
evaluation O
of O
the O
effect O
of O
d B
- I
ribose I
on O
adriamycin B
- O
evoked O
cardiotoxicity O
in O
rats O
. O

The O
influence O
of O
d B
- I
ribose I
on O
adriamycin B
- O
induced O
myocardiopathy O
in O
rats O
was O
studied O
. O

Adriamycin B
in O
the O
cumulative O
dose O
of O
25 O
mg O
/ O
kg O
evoked O
fully O
developed O
cardiac O
toxicity O
. O

D B
- I
ribose I
in O
the O
multiple O
doses O
of O
200 O
mg O
/ O
kg O
did O
not O
influence O
ADR B
cardiotoxicity O
. O

In O
vivo O
evidences O
suggesting O
the O
role O
of O
oxidative O
stress O
in O
pathogenesis O
of O
vancomycin B
- O
induced O
nephrotoxicity O
: O
protection O
by O
erdosteine B
. O

The O
aims O
of O
this O
study O
were O
to O
examine O
vancomycin B
( O
VCM B
) O
- O
induced O
oxidative O
stress O
that O
promotes O
production O
of O
reactive O
oxygen B
species O
( O
ROS O
) O
and O
to O
investigate O
the O
role O
of O
erdosteine B
, O
an O
expectorant O
agent O
, O
which O
has O
also O
antioxidant O
properties O
, O
on O
kidney O
tissue O
against O
the O
possible O
VCM B
- O
induced O
renal O
impairment O
in O
rats O
. O

Rats O
were O
divided O
into O
three O
groups O
: O
sham O
, O
VCM B
and O
VCM B
plus O
erdosteine B
. O

VCM B
was O
administrated O
intraperitoneally O
( O
i O
. O
p O
. O
) O
with O
200mgkg O
( O
- O
1 O
) O
twice O
daily O
for O
7 O
days O
. O

Erdosteine B
was O
administered O
orally O
. O

VCM B
administration O
to O
control O
rats O
significantly O
increased O
renal O
malondialdehyde B
( O
MDA B
) O
and O
urinary O
N O
- O
acetyl O
- O
beta O
- O
d O
- O
glucosaminidase O
( O
NAG O
, O
a O
marker O
of O
renal O
tubular O
injury O
) O
excretion O
but O
decreased O
superoxide B
dismutase O
( O
SOD O
) O
and O
catalase O
( O
CAT O
) O
activities O
. O

Erdosteine B
administration O
with O
VCM B
injections O
caused O
significantly O
decreased O
renal O
MDA B
and O
urinary O
NAG O
excretion O
, O
and O
increased O
SOD O
activity O
, O
but O
not O
CAT O
activity O
in O
renal O
tissue O
when O
compared O
with O
VCM B
alone O
. O

Erdosteine B
showed O
histopathological O
protection O
against O
VCM B
- O
induced O
nephrotoxicity O
. O

There O
were O
a O
significant O
dilatation O
of O
tubular O
lumens O
, O
extensive O
epithelial O
cell O
vacuolization O
, O
atrophy O
, O
desquamation O
, O
and O
necrosis O
in O
VCM B
- O
treated O
rats O
more O
than O
those O
of O
the O
control O
and O
the O
erdosteine B
groups O
. O

Erdosteine B
caused O
a O
marked O
reduction O
in O
the O
extent O
of O
tubular O
damage O
. O

It O
is O
concluded O
that O
oxidative O
tubular O
damage O
plays O
an O
important O
role O
in O
the O
VCM B
- O
induced O
nephrotoxicity O
and O
the O
modulation O
of O
oxidative O
stress O
with O
erdosteine B
reduces O
the O
VCM B
- O
induced O
kidney O
damage O
both O
at O
the O
biochemical O
and O
histological O
levels O
. O

Gemfibrozil B
- O
lovastatin B
therapy O
for O
primary O
hyperlipoproteinemias O
. O

The O
specific O
aim O
of O
this O
retrospective O
, O
observational O
study O
was O
to O
assess O
safety O
and O
efficacy O
of O
long O
- O
term O
( O
21 O
months O
/ O
patient O
) O
, O
open O
- O
label O
, O
gemfibrozil B
- O
lovastatin B
treatment O
in O
80 O
patients O
with O
primary O
mixed O
hyperlipidemia O
( O
68 O
% O
of O
whom O
had O
atherosclerotic O
vascular O
disease O
) O
. O

Because O
ideal O
lipid O
targets O
were O
not O
reached O
( O
low O
- O
density O
lipoprotein O
( O
LDL O
) O
cholesterol B
less O
than O
130 O
mg O
/ O
dl O
, O
high O
- O
density O
lipoprotein O
( O
HDL O
) O
cholesterol B
greater O
than O
35 O
mg O
/ O
dl O
, O
or O
total O
cholesterol B
/ O
HDL O
cholesterol B
less O
than O
4 O
. O
5 O
mg O
/ O
dl O
) O
with O
diet O
plus O
a O
single O
drug O
, O
gemfibrozil B
( O
1 O
. O
2 O
g O
/ O
day O
) O
- O
lovastatin B
( O
primarily O
20 O
or O
40 O
mg O
) O
treatment O
was O
given O
. O

Follow O
- O
up O
visits O
were O
scheduled O
with O
2 O
- O
drug O
therapy O
every O
6 O
to O
8 O
weeks O
, O
an O
average O
of O
10 O
. O
3 O
visits O
per O
patient O
, O
with O
741 O
batteries O
of O
6 O
liver O
function O
tests O
and O
714 O
creatine B
phosphokinase O
levels O
measured O
. O

Only O
1 O
of O
the O
4 O
, O
446 O
liver O
function O
tests O
( O
0 O
. O
02 O
% O
) O
, O
a O
gamma O
glutamyl O
transferase O
, O
was O
greater O
than O
or O
equal O
to O
3 O
times O
the O
upper O
normal O
limit O
. O

Of O
the O
714 O
creatine B
phosphokinase O
levels O
, O
9 O
% O
were O
high O
; O
only O
1 O
( O
0 O
. O
1 O
% O
) O
was O
greater O
than O
or O
equal O
to O
3 O
times O
the O
upper O
normal O
limit O
. O

With O
2 O
- O
drug O
therapy O
, O
mean O
total O
cholesterol B
decreased O
22 O
% O
from O
255 O
to O
200 O
mg O
/ O
dl O
, O
triglyceride B
levels O
decreased O
35 O
% O
from O
236 O
to O
154 O
mg O
/ O
dl O
, O
LDL O
cholesterol B
decreased O
26 O
% O
from O
176 O
to O
131 O
mg O
/ O
dl O
, O
and O
the O
total O
cholesterol B
/ O
HDL O
cholesterol B
ratio O
decreased O
24 O
% O
from O
7 O
. O
1 O
to O
5 O
. O
4 O
, O
all O
p O
less O
than O
or O
equal O
to O
0 O
. O
0001 O
. O

Myositis O
, O
attributable O
to O
the O
drug O
combination O
and O
symptomatic O
enough O
to O
discontinue O
it O
, O
occurred O
in O
3 O
% O
of O
patients O
, O
and O
in O
1 O
% O
with O
concurrent O
high O
creatine B
phosphokinase O
( O
769 O
U O
/ O
liter O
) O
; O
no O
patients O
had O
rhabdomyolysis O
or O
myoglobinuria O
. O
( O
ABSTRACT O
TRUNCATED O
AT O
250 O
WORDS O
) O

Does O
domperidone B
potentiate O
mirtazapine B
- O
associated O
restless O
legs O
syndrome O
? O

There O
is O
now O
evidence O
to O
suggest O
a O
central O
role O
for O
the O
dopaminergic O
system O
in O
restless O
legs O
syndrome O
( O
RLS O
) O
. O

For O
example O
, O
the O
symptoms O
of O
RLS O
can O
be O
dramatically O
improved O
by O
levodopa B
and O
dopamine B
agonists O
, O
whereas O
central O
dopamine B
D2 O
receptor O
antagonists O
can O
induce O
or O
aggravate O
RLS O
symptoms O
. O

To O
our O
knowledge O
, O
there O
is O
no O
previous O
report O
regarding O
whether O
domperidone B
, O
a O
peripheral O
dopamine B
D2 O
receptor O
antagonist O
, O
can O
also O
induce O
or O
aggravate O
symptoms O
of O
RLS O
. O

Mirtazapine B
, O
the O
first O
noradrenergic O
and O
specific O
serotonergic O
antidepressant B
( O
NaSSA O
) O
, O
has O
been O
associated O
with O
RLS O
in O
several O
recent O
publications O
. O

The O
authors O
report O
here O
a O
depressed O
patient O
comorbid O
with O
postprandial O
dyspepsia O
who O
developed O
RLS O
after O
mirtazapine B
had O
been O
added O
to O
his O
domperidone B
therapy O
. O

Our O
patient O
started O
to O
have O
symptoms O
of O
RLS O
only O
after O
he O
had O
been O
treated O
with O
mirtazapine B
, O
and O
his O
RLS O
symptoms O
resolved O
completely O
upon O
discontinuation O
of O
his O
mirtazapine B
. O

Such O
a O
temporal O
relationship O
between O
the O
use O
of O
mirtazapine B
and O
the O
symptoms O
of O
RLS O
in O
our O
patient O
did O
not O
support O
a O
potentiating O
effect O
of O
domperione B
on O
mirtazapine B
- O
associated O
RLS O
. O

However O
, O
physicians O
should O
be O
aware O
of O
the O
possibility O
that O
mirtazapine B
can O
be O
associated O
with O
RLS O
in O
some O
individuals O
, O
especially O
those O
receiving O
concomitant O
dopamine B
D2 O
receptor O
antagonists O
. O

Antiandrogenic O
therapy O
can O
cause O
coronary O
arterial O
disease O
. O

AIM O
: O
To O
study O
the O
change O
of O
lipid O
metabolism O
by O
antiandrogen B
therapy O
in O
patients O
with O
prostate O
cancer O
. O

MATERIALS O
AND O
METHODS O
: O
We O
studied O
with O
a O
2 O
. O
5 O
years O
follow O
- O
up O
the O
changes O
in O
plasma O
cholesterols B
( O
C O
) O
, O
triglycerides B
( O
TG B
) O
, O
lipoproteins O
( O
LP O
) O
, O
and O
apolipoproteins O
( O
Apo O
) O
B O
- O
100 O
, O
A O
- O
I O
, O
and O
A O
- O
II O
pro O
fi O
les O
in O
24 O
patients O
of O
mean O
age O
60 O
years O
with O
low O
risk O
prostate O
cancer O
( O
stage O
: O
T1cN0M0 O
, O
Gleason O
score O
: O
2 O
- O
5 O
) O
during O
treatment O
with O
cyproterone B
acetate I
( O
CPA B
) O
without O

surgical O
management O
or O
radiation O
therapy O
. O

RESULTS O
: O
Significant O
decreases O
of O
HDL O
- O
C O
, O
Apo O
A O
- O
I O
and O
Apo O
A O
- O
II O
and O
an O
increase O
of O
triglyceride B
levels O
in O
VLDL O
were O
induced O
by O
CPA B
. O

After O
a O
period O
of O
2 O
. O
5 O
years O
on O
CPA B
treatment O
, O
four O
patients O
out O
of O
twenty O
- O
four O
were O
found O
to O
be O
affected O
by O
coronary O
heart O
disease O
. O

CONCLUSIONS O
: O
Ischaemic O
coronary O
arteriosclerosis O
with O
an O
incidence O
rate O
of O
16 O
. O
6 O
% O
as O
caused O
by O
prolonged O
CPA B
therapy O
is O
mediated O
through O
changes O
in O
HDL O
cholesterol B
, O
Apo O
A O
- O
I O
and O
Apo O
A O
- O
II O
pro O
fi O
les O
, O
other O
than O
the O
well O
- O
known O
hyperglyceridemic O
effect O
caused O
by O
estrogen B
. O

5 B
- I
Fluorouracil I
cardiotoxicity O
induced O
by O
alpha B
- I
fluoro I
- I
beta I
- I
alanine I
. O

Cardiotoxicity O
is O
a O
rare O
complication O
occurring O
during O
5 B
- I
fluorouracil I
( O
5 B
- I
FU I
) O
treatment O
for O
malignancies O
. O

We O
herein O
report O
the O
case O
of O
a O
70 O
- O
year O
- O
old O
man O
with O
5 B
- I
FU I
- O
induced O
cardiotoxicity O
, O
in O
whom O
a O
high O
serum O
level O
of O
alpha B
- I
fluoro I
- I
beta I
- I
alanine I
( O
FBAL B
) O
was O
observed O
. O

The O
patient O
, O
who O
had O
unresectable O
colon O
cancer O
metastases O
to O
the O
liver O
and O
lung O
, O
was O
referred O
to O
us O
for O
chemotherapy O
from O
an O
affiliated O
hospital O
; O
he O
had O
no O
cardiac O
history O
. O

After O
admission O
, O
the O
patient O
received O
a O
continuous O
intravenous O
infusion O
of O
5 B
- I
FU I
( O
1000 O
mg O
/ O
day O
) O
, O
during O
which O
precordial O
pain O
with O
right O
bundle O
branch O
block O
occurred O
concomitantly O
with O
a O
high O
serum O
FBAL O
concentration O
of O
1955 O
ng O
/ O
ml O
. O

Both O
the O
precordial O
pain O
and O
the O
electrocardiographic O
changes O
disappeared O
spontaneously O
after O
the O
discontinuation O
of O
5 B
- I
FU I
. O

As O
the O
precordial O
pain O
in O
this O
patient O
was O
considered O
to O
have O
been O
due O
to O
5 B
- I
FU I
- O
induced O
cardiotoxicity O
, O
the O
administration O
of O
5 B
- I
FU I
was O
abandoned O
. O

Instead O
, O
oral O
administration O
of O
S O
- O
1 O
( O
a O
derivative O
of O
5 B
- I
FU I
) O
, O
at O
200 O
mg O
/ O
day O
twice O
a O
week O
, O
was O
instituted O
, O
because O
S O
- O
1 O
has O
a O
strong O
inhibitory O
effect O
on O
dihydropyrimidine O
dehydrogenase O
, O
which O
catalyzes O
the O
degradative O
of O
5 B
- I
FU I
into O
FBAL O
. O

The O
serum O
FBAL B
concentration O
subsequently O
decreased O
to O
352 O
ng O
/ O
ml O
, O
the O
same O
as O
the O
value O
measured O
on O
the O
first O
day O
of O
S O
- O
1 O
administration O
. O

Thereafter O
, O
no O
cardiac O
symptoms O
were O
observed O
. O

The O
patient O
achieved O
a O
partial O
response O
6 O
months O
after O
the O
initiation O
of O
the O
S O
- O
1 O
treatment O
. O

The O
experience O
of O
this O
case O
, O
together O
with O
a O
review O
of O
the O
literature O
, O
suggests O
that O
FBAL B
is O
related O
to O
5 B
- I
FU I
- O
induced O
cardiotoxicity O
. O

S O
- O
1 O
may O
be O
administered O
safely O
to O
patients O
with O
5 B
- I
FU I
- O
induced O
cardiotoxicity O
. O

Hepatocellular O
carcinoma O
in O
Fanconi O
' O
s O
anemia O
treated O
with O
androgen B
and O
corticosteroid O
. O

The O
case O
of O
an O
11 O
- O
year O
- O
old O
boy O
is O
reported O
who O
was O
known O
to O
have O
Fanconi O
' O
s O
anemia O
for O
3 O
years O
and O
was O
treated O
with O
androgens B
, O
corticosteroids O
and O
transfusions O
. O

Two O
weeks O
before O
his O
death O
he O
was O
readmitted O
because O
of O
aplastic O
crisis O
with O
septicemia O
and O
marked O
abnormalities O
in O
liver O
function O
and O
died O
of O
hemorrhagic O
bronchopneumonia O
. O

At O
autopsy O
peliosis O
and O
multiple O
hepatic O
tumors O
were O
found O
which O
histologically O
proved O
to O
be O
well O
- O
differentiated O
hepatocellular O
carcinoma O
. O

This O
case O
contributes O
to O
the O
previous O
observations O
that O
non O
- O
metastasizing O
hepatic O
neoplasms O
and O
peliosis O
can O
develop O
in O
patients O
with O
androgen O
- O
and O
corticosteroid O
- O
treated O
Fanconi O
' O
s O
anemia O
. O

The O
influence O
of O
the O
time O
interval O
between O
monoHER O
and O
doxorubicin B
administration O
on O
the O
protection O
against O
doxorubicin B
- O
induced O
cardiotoxicity O
in O
mice O
. O

PURPOSE O
: O
Despite O
its O
well O
- O
known O
cardiotoxicity O
, O
the O
anthracyclin B
doxorubicin B
( O
DOX B
) O
continues O
to O
be O
an O
effective O
and O
widely O
used O
chemotherapeutic O
agent O
. O

DOX B
- O
induced O
cardiac O
damage O
presumably O
results O
from O
the O
formation O
of O
free O
radicals O
by O
DOX B
. O

Reactive O
oxygen B
species O
particularly O
affect O
the O
cardiac O
myocytes O
because O
these O
cells O
seem O
to O
have O
a O
relatively O
poor O
antioxidant O
defense O
system O
. O

The O
semisynthetic O
flavonoid B
monohydroxyethylrutoside I
( O
monoHER B
) O
showed O
cardioprotection O
against O
DOX B
- O
induced O
cardiotoxicity O
through O
its O
radical O
scavenging O
and O
iron B
chelating O
properties O
. O

Because O
of O
the O
relatively O
short O
final O
half O
- O
life O
of O
monoHER O
( O
about O
30 O
min O
) O
, O
it O
is O
expected O
that O
the O
time O
interval O
between O
monoHER O
and O
DOX B
might O
be O
of O
influence O
on O
the O
cardioprotective O
effect O
of O
monoHER O
. O

Therefore O
, O
the O
aim O
of O
the O
present O
study O
was O
to O
investigate O
this O
possible O
effect O
. O

METHODS O
: O
Six O
groups O
of O
6 O
BALB O
/ O
c O
mice O
were O
treated O
with O
saline O
, O
DOX B
alone O
or O
DOX B
( O
4 O
mg O
/ O
kg O
i O
. O
v O
. O
) O
preceded O
by O
monoHER O
( O
500 O
mg O
/ O
kg O
i O
. O
p O
. O
) O
with O
an O
interval O
of O
10 O
, O
30 O
, O
60 O
or O
120 O
min O
. O

After O
a O
6 O
- O
week O
treatment O
period O
and O
additional O
observation O
for O
2 O
weeks O
, O
the O
mice O
were O
sacrificed O
. O

Their O
cardiac O
tissues O
were O
processed O
for O
light O
microscopy O
, O
after O
which O
cardiomyocyte O
damage O
was O
evaluated O
according O
to O
Billingham O
( O
in O
Cancer O
Treat O
Rep O
62 O
( O
6 O
) O
: O
865 O
- O
872 O
, O
1978 O
) O
. O

Microscopic O
evaluation O
revealed O
that O
treatment O
with O
DOX B
alone O
induced O
significant O
cardiac O
damage O
in O
comparison O
to O
the O
saline O
control O
group O
( O
P O
< O
0 O
. O
001 O
) O
. O

RESULTS O
: O
The O
number O
of O
damaged O
cardiomyocytes O
was O
9 O
. O
6 O
- O
fold O
( O
95 O
% O
CI O
4 O
. O
4 O
- O
21 O
. O
0 O
) O
higher O
in O
mice O
treated O
with O
DOX B
alone O
than O
that O
in O
animals O
of O
the O
control O
group O
. O

The O
ratio O
of O
aberrant O
cardiomyocytes O
in O
mice O
treated O
with O
DOX B
preceded O
by O
monoHER O
and O
those O
in O
mice O
treated O
with O
saline O
ranged O
from O
1 O
. O
6 O
to O
2 O
. O
8 O
( O
mean O
2 O
. O
2 O
, O
95 O
% O
CI O
1 O
. O
2 O
- O
4 O
. O
1 O
, O
P O
= O
0 O
. O
019 O
) O
. O

The O
mean O
protective O
effect O
by O
adding O
monoHER O
before O
DOX B
led O
to O
a O
significant O
4 O
. O
4 O
- O
fold O
reduction O
( O
P O
< O
0 O
. O
001 O
, O
95 O
% O
CI O
2 O
. O
3 O
- O
8 O
. O
2 O
) O
of O
abnormal O
cardiomyocytes O
. O

This O
protective O
effect O
did O
not O
depend O
on O
the O
time O
interval O
between O
monoHER O
and O
DOX B
administration O
( O
P O
= O
0 O
. O
345 O
) O
. O

CONCLUSION O
: O
The O
results O
indicate O
that O
in O
an O
outpatient O
clinical O
setting O
monoHER O
may O
be O
administered O
shortly O
before O
DOX B
. O

Clinical O
evaluation O
of O
adverse O
effects O
during O
bepridil B
administration O
for O
atrial O
fibrillation O
and O
flutter O
. O

BACKGROUND O
: O
Bepridil B
hydrochloride I
( O
Bpd B
) O
has O
attracted O
attention O
as O
an O
effective O
drug O
for O
atrial O
fibrillation O
( O
AF O
) O
and O
atrial O
flutter O
( O
AFL O
) O
. O

However O
, O
serious O
adverse O
effects O
, O
including O
torsade O
de O
pointes O
( O
Tdp O
) O
, O
have O
been O
reported O
. O

METHODS O
AND O
RESULTS O
: O
Adverse O
effects O
of O
Bpd O
requiring O
discontinuation O
of O
treatment O
were O
evaluated O
. O

Bpd O
was O
administered O
to O
459 O
patients O
( O
361 O
males O
, O
63 O
+ O
/ O
- O
12 O
years O
old O
) O
comprising O
378 O
AF O
and O
81 O
AFL O
cases O
. O

Mean O
left O
ventricular O
ejection O
fraction O
and O
atrial O
dimension O
( O
LAD O
) O
were O
66 O
+ O
/ O
- O
11 O
% O
and O
40 O
+ O
/ O
- O
6 O
mm O
, O
respectively O
. O

Adverse O
effects O
were O
observed O
in O
19 O
patients O
( O
4 O
% O
) O
during O
an O
average O
follow O
- O
up O
of O
20 O
months O
. O

There O
was O
marked O
QT O
prolongation O
greater O
than O
0 O
. O
55 O
s O
in O
13 O
patients O
, O
bradycardia O
less O
than O
40 O
beats O
/ O
min O
in O
6 O
patients O
, O
dizziness O
and O
general O
fatigue O
in O
1 O
patient O
each O
. O

In O
4 O
of O
13 O
patients O
with O
QT O
prolongation O
, O
Tdp O
occurred O
. O

The O
major O
triggering O
factors O
of O
Tdp O
were O
hypokalemia O
and O
sudden O
decrease O
in O
heart O
rate O
. O

There O
were O
no O
differences O
in O
the O
clinical O
backgrounds O
of O
the O
patients O
with O
and O
without O
Tdp O
other O
than O
LAD O
and O
age O
, O
which O
were O
larger O
and O
older O
in O
the O
patients O
with O
Tdp O
. O

CONCLUSION O
: O
Careful O
observation O
of O
serum O
potassium B
concentration O
and O
the O
ECG O
should O
always O
be O
done O
during O
Bpd O
administration O
, O
particularly O
in O
elderly O
patients O
. O

Enhanced O
isoproterenol B
- O
induced O
cardiac O
hypertrophy O
in O
transgenic O
rats O
with O
low O
brain O
angiotensinogen O
. O

We O
have O
previously O
shown O
that O
a O
permanent O
deficiency O
in O
the O
brain O
renin O
- O
angiotensin B
system O
( O
RAS O
) O
may O
increase O
the O
sensitivity O
of O
the O
baroreflex O
control O
of O
heart O
rate O
. O

In O
this O
study O
we O
aimed O
at O
studying O
the O
involvement O
of O
the O
brain O
RAS O
in O
the O
cardiac O
reactivity O
to O
the O
beta O
- O
adrenoceptor O
( O
beta O
- O
AR O
) O
agonist O
isoproterenol B
( O
Iso B
) O
. O

Transgenic O
rats O
with O
low O
brain O
angiotensinogen O
( O
TGR O
) O
were O
used O
. O

In O
isolated O
hearts O
, O
Iso B
induced O
a O
significantly O
greater O
increase O
in O
left O
ventricular O
( O
LV O
) O
pressure O
and O
maximal O
contraction O
( O
+ O
dP O
/ O
dt O
( O
max O
) O
) O
in O
the O
TGR O
than O
in O
the O
Sprague O
- O
Dawley O
( O
SD O
) O
rats O
. O

LV O
hypertrophy O
induced O
by O
Iso B
treatment O
was O
significantly O
higher O
in O
TGR O
than O
in O
SD O
rats O
( O
in O
g O
LV O
wt O
/ O
100 O
g O
body O
wt O
, O
0 O
. O
28 O
+ O
/ O
- O
0 O
. O
004 O
vs O
. O
0 O
. O
24 O
+ O
/ O
- O
0 O
. O
004 O
, O
respectively O
) O
. O

The O
greater O
LV O
hypertrophy O
in O
TGR O
rats O
was O
associated O
with O
more O
pronounced O
downregulation O
of O
beta O
- O
AR O
and O
upregulation O
of O
LV O
beta O
- O
AR O
kinase O
- O
1 O
mRNA O
levels O
compared O
with O
those O
in O
SD O
rats O
. O

The O
decrease O
in O
the O
heart O
rate O
( O
HR O
) O
induced O
by O
the O
beta O
- O
AR O
antagonist O
metoprolol B
in O
conscious O
rats O
was O
significantly O
attenuated O
in O
TGR O
compared O
with O
SD O
rats O
( O
- O
9 O
. O
9 O
+ O
/ O
- O
1 O
. O
7 O
% O
vs O
. O
- O
18 O
. O
1 O
+ O
/ O
- O
1 O
. O
5 O
% O
) O
, O
whereas O
the O
effect O
of O
parasympathetic O
blockade O
by O
atropine B
on O
HR O
was O
similar O
in O
both O
strains O
. O

These O
results O
indicate O
that O
TGR O
are O
more O
sensitive O
to O
beta O
- O
AR O
agonist O
- O
induced O
cardiac O
inotropic O
response O
and O
hypertrophy O
, O
possibly O
due O
to O
chronically O
low O
sympathetic O
outflow O
directed O
to O
the O
heart O
. O

Drug O
- O
induced O
long O
QT O
syndrome O
in O
injection O
drug O
users O
receiving O
methadone B
: O
high O
frequency O
in O
hospitalized O
patients O
and O
risk O
factors O
. O

BACKGROUND O
: O
Drug O
- O
induced O
long O
QT O
syndrome O
is O
a O
serious O
adverse O
drug O
reaction O
. O

Methadone B
prolongs O
the O
QT O
interval O
in O
vitro O
in O
a O
dose O
- O
dependent O
manner O
. O

In O
the O
inpatient O
setting O
, O
the O
frequency O
of O
QT O
interval O
prolongation O
with O
methadone B
treatment O
, O
its O
dose O
dependence O
, O
and O
the O
importance O
of O
cofactors O
such O
as O
drug O
- O
drug O
interactions O
remain O
unknown O
. O

METHODS O
: O
We O
performed O
a O
systematic O
, O
retrospective O
study O
comparing O
active O
or O
former O
intravenous O
drug O
users O
receiving O
methadone B
and O
those O
not O
receiving O
methadone B
among O
all O
patients O
hospitalized O
over O
a O
5 O
- O
year O
period O
in O
a O
tertiary O
care O
hospital O
. O

A O
total O
of O
167 O
patients O
receiving O
methadone B
fulfilled O
the O
inclusion O
criteria O
and O
were O
compared O
with O
a O
control O
group O
of O
80 O
injection O
drug O
users O
not O
receiving O
methadone B
. O

In O
addition O
to O
methadone B
dose O
, O
15 O
demographic O
, O
biological O
, O
and O
pharmacological O
variables O
were O
considered O
as O
potential O
risk O
factors O
for O
QT O
prolongation O
. O

RESULTS O
: O
Among O
167 O
methadone B
maintenance O
patients O
, O
the O
prevalence O
of O
QTc O
prolongation O
to O
0 O
. O
50 O
second O
( O
( O
1 O
/ O
2 O
) O
) O
or O
longer O
was O
16 O
. O
2 O
% O
compared O
with O
0 O
% O
in O
80 O
control O
subjects O
. O

Six O
patients O
( O
3 O
. O
6 O
% O
) O
in O
the O
methadone B
group O
presented O
torsades O
de O
pointes O
. O

QTc O
length O
was O
weakly O
but O
significantly O
associated O
with O
methadone B
daily O
dose O
( O
Spearman O
rank O
correlation O
coefficient O
, O
0 O
. O
20 O
; O
P O
< O
. O
01 O
) O
. O

Multivariate O
regression O
analysis O
allowed O
attribution O
of O
31 O
. O
8 O
% O
of O
QTc O
variability O
to O
methadone B
dose O
, O
cytochrome O
P O
- O
450 O
3A4 O
drug O
- O
drug O
interactions O
, O
hypokalemia O
, O
and O
altered O
liver O
function O
. O

CONCLUSIONS O
: O
QT O
interval O
prolongation O
in O
methadone B
maintenance O
patients O
hospitalized O
in O
a O
tertiary O
care O
center O
is O
a O
frequent O
finding O
. O

Methadone B
dose O
, O
presence O
of O
cytochrome O
P O
- O
450 O
3A4 O
inhibitors O
, O
potassium B
level O
, O
and O
liver O
function O
contribute O
to O
QT O
prolongation O
. O

Long O
QT O
syndrome O
can O
occur O
with O
low O
doses O
of O
methadone B
. O

Mechanisms O
of O
hypertension O
induced O
by O
nitric B
oxide I
( O
NO B
) O
deficiency O
: O
focus O
on O
venous O
function O
. O

Loss O
of O
endothelial O
cell O
- O
derived O
nitric B
oxide I
( O
NO B
) O
in O
hypertension O
is O
a O
hallmark O
of O
arterial O
dysfunction O
. O

Experimental O
hypertension O
created O
by O
the O
removal O
of O
NO B
, O
however O
, O
involves O
mechanisms O
in O
addition O
to O
decreased O
arterial O
vasodilator O
activity O
. O

These O
include O
augmented O
endothelin O
- O
1 O
( O
ET O
- O
1 O
) O
release O
, O
increased O
sympathetic O
nervous O
system O
activity O
, O
and O
elevated O
tissue O
oxidative O
stress O
. O

We O
hypothesized O
that O
increased O
venous O
smooth O
muscle O
( O
venomotor O
) O
tone O
plays O
a O
role O
in O
Nomega B
- I
nitro I
- I
L I
- I
arginine I
( O
LNNA B
) O
hypertension O
through O
these O
mechanisms O
. O

Rats O
were O
treated O
with O
the O
NO B
synthase O
inhibitor O
LNNA B
( O
0 O
. O
5 O
g O
/ O
L O
in O
drinking O
water O
) O
for O
2 O
weeks O
. O

Mean O
arterial O
pressure O
of O
conscious O
rats O
was O
119 O
+ O
/ O
- O
2 O
mm O
Hg O
in O
control O
and O
194 O
+ O
/ O
- O
5 O
mm O
Hg O
in O
LNNA O
rats O
( O
P O
< O
0 O
. O
05 O
) O
. O

Carotid O
arteries O
and O
vena O
cava O
were O
removed O
for O
measurement O
of O
isometric O
contraction O
. O

Maximal O
contraction O
to O
norepinephrine B
was O
modestly O
reduced O
in O
arteries O
from O
LNNA O
compared O
with O
control O
rats O
whereas O
the O
maximum O
contraction O
to O
ET O
- O
1 O
was O
significantly O
reduced O
( O
54 O
% O
control O
) O
. O

Maximum O
contraction O
of O
vena O
cava O
to O
norepinephrine B
( O
37 O
% O
control O
) O
also O
was O
reduced O
but O
no O
change O
in O
response O
to O
ET O
- O
1 O
was O
observed O
. O

Mean O
circulatory O
filling O
pressure O
, O
an O
in O
vivo O
measure O
of O
venomotor O
tone O
, O
was O
not O
elevated O
in O
LNNA O
hypertension O
at O
1 O
or O
2 O
weeks O
after O
LNNA O
. O

The O
superoxide B
scavenger O
tempol B
( O
30 O
, O
100 O
, O
and O
300 O
micromol O
kg O
( O
- O
1 O
) O
, O
IV O
) O
did O
not O
change O
arterial O
pressure O
in O
control O
rats O
but O
caused O
a O
dose O
- O
dependent O
decrease O
in O
LNNA O
rats O
( O
- O
18 O
+ O
/ O
- O
8 O
, O
- O
26 O
+ O
/ O
- O
15 O
, O
and O
- O
54 O
+ O
/ O
- O
11 O
mm O
Hg O
) O
. O

Similarly O
, O
ganglionic O
blockade O
with O
hexamethonium B
caused O
a O
significantly O
greater O
fall O
in O
LNNA O
hypertensive O
rats O
( O
76 O
+ O
/ O
- O
9 O
mm O
Hg O
) O
compared O
with O
control O
rats O
( O
35 O
+ O
/ O
- O
10 O
mm O
Hg O
) O
. O

Carotid O
arteries O
, O
vena O
cava O
, O
and O
sympathetic O
ganglia O
from O
LNNA O
rats O
had O
higher O
basal O
levels O
of O
superoxide B
compared O
with O
those O
from O
control O
rats O
. O

These O
data O
suggest O
that O
while O
NO B
deficiency O
increases O
oxidative O
stress O
and O
sympathetic O
activity O
in O
both O
arterial O
and O
venous O
vessels O
, O
the O
impact O
on O
veins O
does O
not O
make O
a O
major O
contribution O
to O
this O
form O
of O
hypertension O
. O

Association O
of O
DRD2 O
polymorphisms O
and O
chlorpromazine B
- O
induced O
extrapyramidal O
syndrome O
in O
Chinese O
schizophrenic O
patients O
. O

AIM O
: O
Extrapyramidal O
syndrome O
( O
EPS O
) O
is O
most O
commonly O
affected O
by O
typical O
antipsychotic O
drugs O
that O
have O
a O
high O
affinity O
with O
the O
D2 O
receptor O
. O

Recently O
, O
many O
research O
groups O
have O
reported O
on O
the O
positive O
relationship O
between O
the O
genetic O
variations O
in O
the O
DRD2 O
gene O
and O
the O
therapeutic O
response O
in O
schizophrenia O
patients O
as O
a O
result O
of O
the O
role O
of O
variations O
in O
the O
receptor O
in O
modulating O
receptor O
expression O
. O

In O
this O
study O
, O
we O
evaluate O
the O
role O
DRD2 O
plays O
in O
chlorpromazine B
- O
induced O
EPS O
in O
schizophrenic O
patients O
. O

METHODS O
: O
We O
identified O
seven O
SNP O
( O
single O
nucleotide O
polymorphism O
) O
( O
- O
141Cins O
> O
del O
, O
TaqIB O
, O
TaqID O
, O
Ser311Cys O
, O
rs6275 O
, O
rs6277 O
and O
TaqIA O
) O
in O
the O
DRD2 O
gene O
in O
146 O
schizophrenic O
inpatients O
( O
59 O
with O
EPS O
and O
87 O
without O
EPS O
according O
to O
the O
Simpson O
- O
Angus O
Scale O
) O
treated O
with O
chlorpromazine B
after O
8 O
weeks O
. O

The O
alleles O
of O
all O
loci O
were O
determined O
by O
PCR O
( O
polymerase O
chain O
reaction O
) O
. O

RESULTS O
: O
Polymorphisms O
TaqID O
, O
Ser311Cys O
and O
rs6277 O
were O
not O
polymorphic O
in O
the O
population O
recruited O
in O
the O
present O
study O
. O

No O
statistical O
significance O
was O
found O
in O
the O
allele O
distribution O
of O
- O
141Cins O
> O
del O
, O
TaqIB O
, O
rs6275 O
and O
TaqIA O
or O
in O
the O
estimated O
haplotypes O
( O
constituted O
by O
TaqIB O
, O
rs6275 O
and O
TaqIA O
) O
in O
linkage O
disequilibrium O
between O
the O
two O
groups O
. O

CONCLUSION O
: O
Our O
results O
did O
not O
lend O
strong O
support O
to O
the O
view O
that O
the O
genetic O
variation O
of O
the O
DRD2 O
gene O
plays O
a O
major O
role O
in O
the O
individually O
variable O
adverse O
effect O
induced O
by O
chlorpromazine B
, O
at O
least O
in O
Chinese O
patients O
with O
schizophrenia O
. O

Our O
results O
confirmed O
a O
previous O
study O
on O
the O
relationship O
between O
DRD2 O
and O
EPS O
in O
Caucasians O
. O

Physical O
training O
decreases O
susceptibility O
to O
subsequent O
pilocarpine B
- O
induced O
seizures O
in O
the O
rat O
. O

Regular O
motor O
activity O
has O
many O
benefits O
for O
mental O
and O
physical O
condition O
but O
its O
implications O
for O
epilepsy O
are O
still O
controversial O
. O

In O
order O
to O
elucidate O
this O
problem O
, O
we O
have O
studied O
the O
effect O
of O
long O
- O
term O
physical O
activity O
on O
susceptibility O
to O
subsequent O
seizures O
. O

Male O
Wistar O
rats O
were O
subjected O
to O
repeated O
training O
sessions O
in O
a O
treadmill O
and O
swimming O
pool O
. O

Thereafter O
, O
seizures O
were O
induced O
by O
pilocarpine B
injections O
in O
trained O
and O
non O
- O
trained O
control O
groups O
. O

During O
the O
acute O
period O
of O
status O
epilepticus O
, O
we O
measured O
: O
( O
1 O
) O
the O
latency O
of O
the O
first O
motor O
sign O
, O
( O
2 O
) O
the O
intensity O
of O
seizures O
, O
( O
3 O
) O
the O
time O
when O
it O
occurred O
within O
the O
6 O
- O
h O
observation O
period O
, O
and O
( O
4 O
) O
the O
time O
when O
the O
acute O
period O
ended O
. O

All O
these O
behavioral O
parameters O
showed O
statistically O
significant O
changes O
suggesting O
that O
regular O
physical O
exercises O
decrease O
susceptibility O
to O
subsequently O
induced O
seizures O
and O
ameliorate O
the O
course O
of O
experimentally O
induced O
status O
epilepticus O
. O

Tonic O
dopaminergic O
stimulation O
impairs O
associative O
learning O
in O
healthy O
subjects O
. O

Endogenous O
dopamine B
plays O
a O
central O
role O
in O
salience O
coding O
during O
associative O
learning O
. O

Administration O
of O
the O
dopamine B
precursor O
levodopa B
enhances O
learning O
in O
healthy O
subjects O
and O
stroke O
patients O
. O

Because O
levodopa B
increases O
both O
phasic O
and O
tonic O
dopaminergic O
neurotransmission O
, O
the O
critical O
mechanism O
mediating O
the O
enhancement O
of O
learning O
is O
unresolved O
. O

We O
here O
probed O
how O
selective O
tonic O
dopaminergic O
stimulation O
affects O
associative O
learning O
. O

Forty O
healthy O
subjects O
were O
trained O
in O
a O
novel O
vocabulary O
of O
45 O
concrete O
nouns O
over O
the O
course O
of O
5 O
consecutive O
training O
days O
in O
a O
prospective O
, O
randomized O
, O
double O
- O
blind O
, O
placebo O
- O
controlled O
design O
. O

Subjects O
received O
the O
tonically O
stimulating O
dopamine B
- O
receptor O
agonist O
pergolide B
( O
0 O
. O
1 O
mg O
) O
vs O
placebo O
120 O
min O
before O
training O
on O
each O
training O
day O
. O

The O
dopamine B
agonist O
significantly O
impaired O
novel O
word O
learning O
compared O
to O
placebo O
. O

This O
learning O
decrement O
persisted O
up O
to O
the O
last O
follow O
- O
up O
4 O
weeks O
post O
- O
training O
. O

Subjects O
treated O
with O
pergolide B
also O
showed O
restricted O
emotional O
responses O
compared O
to O
the O
PLACEBO O
group O
. O

The O
extent O
of O
' O
flattened O
' O
affect O
with O
pergolide B
was O
related O
to O
the O
degree O
of O
learning O
inhibition O
. O

These O
findings O
suggest O
that O
tonic O
occupation O
of O
dopamine B
receptors O
impairs O
learning O
by O
competition O
with O
phasic O
dopamine B
signals O
. O

Thus O
, O
phasic O
signaling O
seems O
to O
be O
the O
critical O
mechanism O
by O
which O
dopamine B
enhances O
associative O
learning O
in O
healthy O
subjects O
and O
stroke O
patients O
. O

Minocycline B
- O
induced O
vasculitis O
fulfilling O
the O
criteria O
of O
polyarteritis O
nodosa O
. O

A O
47 O
- O
year O
- O
old O
man O
who O
had O
been O
taking O
minocycline B
for O
palmoplantar O
pustulosis O
developed O
fever O
, O
myalgias O
, O
polyneuropathy O
, O
and O
testicular O
pain O
, O
with O
elevated O
C O
- O
reactive O
protein O
( O
CRP O
) O
. O

Neither O
myeloperoxidase O
- O
nor O
proteinase O
- O
3 O
- O
antineutrophil O
cytoplasmic O
antibody O
was O
positive O
. O

These O
manifestations O
met O
the O
American O
College O
of O
Rheumatology O
1990 O
criteria O
for O
the O
classification O
of O
polyarteritis O
nodosa O
. O

Stopping O
minocycline B
led O
to O
amelioration O
of O
symptoms O
and O
normalization O
of O
CRP O
level O
. O

To O
our O
knowledge O
, O
this O
is O
the O
second O
case O
of O
minocycline B
- O
induced O
vasculitis O
satisfying O
the O
criteria O
. O

Differential O
diagnosis O
for O
drug O
- O
induced O
disease O
is O
invaluable O
even O
for O
patients O
with O
classical O
polyarteritis O
nodosa O
. O

Intramuscular O
hepatitis O
B O
immune O
globulin O
combined O
with O
lamivudine B
in O
prevention O
of O
hepatitis O
B O
recurrence O
after O
liver O
transplantation O
. O

BACKGROUND O
: O
Combined O
hepatitis O
B O
immune O
globulin O
( O
HBIg O
) O
and O
lamivudine B
in O
prophylaxis O
of O
the O
recurrence O
of O
hepatitis O
B O
after O
liver O
transplantation O
has O
significantly O
improved O
the O
survival O
of O
HBsAg B
positive O
patients O
. O

This O
study O
was O
undertaken O
to O
evaluate O
the O
outcomes O
of O
liver O
transplantation O
for O
patients O
with O
hepatitis O
B O
virus O
( O
HBV O
) O
. O

METHODS O
: O
A O
retrospective O
chart O
analysis O
and O
a O
review O
of O
the O
organ O
transplant O
database O
identified O
51 O
patients O
( O
43 O
men O
and O
8 O
women O
) O
transplanted O
for O
benign O
HBV O
- O
related O
cirrhotic O
diseases O
between O
June O
2002 O
and O
December O
2004 O
who O
had O
survived O
more O
than O
3 O
months O
. O

HBIg O
was O
administered O
intravenously O
during O
the O
first O
week O
and O
intramuscularly O
thereafter O
. O

RESULTS O
: O
At O
a O
median O
follow O
- O
up O
of O
14 O
. O
1 O
months O
, O
the O
overall O
recurrence O
rate O
in O
the O
51 O
patients O
was O
3 O
. O
9 O
% O
( O
2 O
/ O
51 O
) O
. O

The O
overall O
patient O
survival O
was O
88 O
. O
3 O
% O
, O
and O
82 O
. O
4 O
% O
after O
1 O
and O
2 O
years O
, O
respectively O
. O

A O
daily O
oral O
dose O
of O
100 O
mg O
lamivudine B
for O
2 O
weeks O
before O
transplantation O
for O
10 O
patients O
enabled O
57 O
. O
1 O
% O
( O
4 O
/ O
7 O
) O
and O
62 O
. O
5 O
% O
( O
5 O
/ O
8 O
) O
of O
HBV O
- O
DNA O
and O
HBeAg B
positive O
patients O
respectively O
to O
convert O
to O
be O
negative O
. O

Intramuscular O
HBIg O
was O
well O
tolerated O
in O
all O
patients O
. O

CONCLUSION O
: O
Lamivudine B
combined O
with O
intramuscular O
HBIg O
can O
effectively O
prevent O
allograft O
from O
the O
recurrence O
of O
HBV O
after O
liver O
transplantation O
. O

Anticonvulsant O
effect O
of O
eslicarbazepine B
acetate I
( O
BIA B
2 I
- I
093 I
) O
on O
seizures O
induced O
by O
microperfusion O
of O
picrotoxin B
in O
the O
hippocampus O
of O
freely O
moving O
rats O
. O

Eslicarbazepine B
acetate I
( O
BIA B
2 I
- I
093 I
, O
S B
- I
( I
- I
) I
- I
10 I
- I
acetoxy I
- I
10 I
, I
11 I
- I
dihydro I
- I
5H I
- I
dibenzo I
/ I
b I
, I
f I
/ I
azepine I
- I
5 I
- I
carboxamide I
) O
is O
a O
novel O
antiepileptic O
drug O
, O
now O
in O
Phase O
III O
clinical O
trials O
, O
designed O
with O
the O
aim O
of O
improving O
efficacy O
and O
safety O
in O
comparison O
with O
the O
structurally O
related O
drugs O
carbamazepine B
( O
CBZ B
) O
and O
oxcarbazepine B
( O
OXC B
) O
. O

We O
have O
studied O
the O
effects O
of O
oral O
treatment O
with O
eslicarbazepine B
acetate I
on O
a O
whole O
- O
animal O
model O
in O
which O
partial O
seizures O
can O
be O
elicited O
repeatedly O
on O
different O
days O
without O
changes O
in O
threshold O
or O
seizure O
patterns O
. O

In O
the O
animals O
treated O
with O
threshold O
doses O
of O
picrotoxin B
, O
the O
average O
number O
of O
seizures O
was O
2 O
. O
3 O
+ O
/ O
- O
1 O
. O
2 O
, O
and O
average O
seizure O
duration O
was O
39 O
. O
5 O
+ O
/ O
- O
8 O
. O
4s O
. O

Pre O
- O
treatment O
with O
a O
dose O
of O
30 O
mg O
/ O
kg O
2h O
before O
picrotoxin B
microperfusion O
prevented O
seizures O
in O
the O
75 O
% O
of O
the O
rats O
. O

Lower O
doses O
( O
3 O
and O
10mg O
/ O
kg O
) O
did O
not O
suppress O
seizures O
, O
however O
, O
after O
administration O
of O
10mg O
/ O
kg O
, O
significant O
reductions O
in O
seizures O
duration O
( O
24 O
. O
3 O
+ O
/ O
- O
6 O
. O
8s O
) O
and O
seizure O
number O
( O
1 O
. O
6 O
+ O
/ O
- O
0 O
. O
34 O
) O
were O
found O
. O

No O
adverse O
effects O
of O
eslicarbazepine B
acetate I
were O
observed O
in O
the O
behavioral O
/ O
EEG O
patterns O
studied O
, O
including O
sleep O
/ O
wakefulness O
cycle O
, O
at O
the O
doses O
studied O
. O

Acute O
renal O
failure O
associated O
with O
prolonged O
intake O
of O
slimming O
pills O
containing O
anthraquinones B
. O

Chinese O
herbal O
medicine O
preparations O
are O
widely O
available O
and O
often O
regarded O
by O
the O
public O
as O
natural O
and O
safe O
remedies O
for O
a O
variety O
of O
medical O
conditions O
. O

Nephropathy O
caused O
by O
Chinese O
herbs O
has O
previously O
been O
reported O
, O
usually O
involving O
the O
use O
of O
aristolochic B
acids I
. O

We O
report O
a O
23 O
- O
year O
- O
old O
woman O
who O
developed O
acute O
renal O
failure O
following O
prolonged O
use O
of O
a O
proprietary O
Chinese O
herbal O
slimming O
pill O
that O
contained O
anthraquinone B
derivatives O
, O
extracted O
from O
Rhizoma O
Rhei I
( O
rhubarb B
) O
. O

The O
renal O
injury O
was O
probably O
aggravated O
by O
the O
concomitant O
intake O
of O
a O
non O
- O
steroidal O
anti O
- O
inflammatory O
drug O
, O
diclofenac B
. O

Renal O
pathology O
was O
that O
of O
hypocellular O
interstitial O
fibrosis O
. O

Spontaneous O
renal O
recovery O
occurred O
upon O
cessation O
of O
the O
slimming O
pills O
, O
but O
mild O
interstitial O
fibrosis O
and O
tubular O
atrophy O
was O
still O
evident O
histologically O
4 O
months O
later O
. O

Although O
a O
causal O
relationship O
between O
the O
use O
of O
an O
anthraquinone B
- O
containing O
herbal O
agent O
and O
renal O
injury O
remains O
to O
be O
proven O
, O
phytotherapy O
- O
associated O
interstitial O
nephropathy O
should O
be O
considered O
in O
patients O
who O
present O
with O
unexplained O
renal O
failure O
. O

Chloroacetaldehyde B
as O
a O
sulfhydryl O
reagent O
: O
the O
role O
of O
critical O
thiol B
groups O
in O
ifosfamide B
nephropathy O
. O

Chloroacetaldehyde B
( O
CAA B
) O
is O
a O
metabolite O
of O
the O
alkylating O
agent O
ifosfamide B
( O
IFO B
) O
and O
putatively O
responsible O
for O
renal O
damage O
following O
anti O
- O
tumor O
therapy O
with O
IFO B
. O

Depletion O
of O
sulfhydryl O
( O
SH O
) O
groups O
has O
been O
reported O
from O
cell O
culture O
, O
animal O
and O
clinical O
studies O
. O

In O
this O
work O
the O
effect O
of O
CAA B
on O
human O
proximal O
tubule O
cells O
in O
primary O
culture O
( O
hRPTEC O
) O
was O
investigated O
. O

Toxicity O
of O
CAA B
was O
determined O
by O
protein O
content O
, O
cell O
number O
, O
LDH O
release O
, O
trypan O
blue O
exclusion O
assay O
and O
caspase O
- O
3 O
activity O
. O

Free O
thiols B
were O
measured O
by O
the O
method O
of O
Ellman O
. O

CAA B
reduced O
hRPTEC O
cell O
number O
and O
protein O
, O
induced O
a O
loss O
in O
free O
intracellular O
thiols B
and O
an O
increase O
in O
necrosis O
markers O
. O

CAA B
but O
not O
acrolein B
inhibited O
the O
cysteine O
proteases O
caspase O
- O
3 O
, O
caspase O
- O
8 O
and O
cathepsin O
B O
. O

Caspase O
activation O
by O
cisplatin B
was O
inhibited O
by O
CAA B
. O

In O
cells O
stained O
with O
fluorescent O
dyes O
targeting O
lysosomes O
, O
CAA B
induced O
an O
increase O
in O
lysosomal O
size O
and O
lysosomal O
leakage O
. O

The O
effects O
of O
CAA B
on O
cysteine B
protease O
activities O
and O
thiols B
could O
be O
reproduced O
in O
cell O
lysate O
. O

Acidification O
, O
which O
slowed O
the O
reaction O
of O
CAA B
with O
thiol B
donors O
, O
could O
also O
attenuate O
effects O
of O
CAA B
on O
necrosis O
markers O
, O
thiol B
depletion O
and O
cysteine B
protease O
inhibition O
in O
living O
cells O
. O

Thus O
, O
CAA B
directly O
reacts O
with O
cellular O
protein O
and O
non O
- O
protein O
thiols B
, O
mediating O
its O
toxicity O
on O
hRPTEC O
. O

This O
effect O
can O
be O
reduced O
by O
acidification O
. O

Therefore O
, O
urinary O
acidification O
could O
be O
an O
option O
to O
prevent O
IFO B
nephropathy O
in O
patients O
. O

Stereological O
methods O
reveal O
the O
robust O
size O
and O
stability O
of O
ectopic O
hilar O
granule O
cells O
after O
pilocarpine B
- O
induced O
status O
epilepticus O
in O
the O
adult O
rat O
. O

Following O
status O
epilepticus O
in O
the O
rat O
, O
dentate O
granule O
cell O
neurogenesis O
increases O
greatly O
, O
and O
many O
of O
the O
new O
neurons O
appear O
to O
develop O
ectopically O
, O
in O
the O
hilar O
region O
of O
the O
hippocampal O
formation O
. O

It O
has O
been O
suggested O
that O
the O
ectopic O
hilar O
granule O
cells O
could O
contribute O
to O
the O
spontaneous O
seizures O
that O
ultimately O
develop O
after O
status O
epilepticus O
. O

However O
, O
the O
population O
has O
never O
been O
quantified O
, O
so O
it O
is O
unclear O
whether O
it O
is O
substantial O
enough O
to O
have O
a O
strong O
influence O
on O
epileptogenesis O
. O

To O
quantify O
this O
population O
, O
the O
total O
number O
of O
ectopic O
hilar O
granule O
cells O
was O
estimated O
using O
unbiased O
stereology O
at O
different O
times O
after O
pilocarpine B
- O
induced O
status O
epilepticus O
. O

The O
number O
of O
hilar O
neurons O
immunoreactive O
for O
Prox O
- O
1 O
, O
a O
granule O
- O
cell O
- O
specific O
marker O
, O
was O
estimated O
using O
the O
optical O
fractionator O
method O
. O

The O
results O
indicate O
that O
the O
size O
of O
the O
hilar O
ectopic O
granule O
cell O
population O
after O
status O
epilepticus O
is O
substantial O
, O
and O
stable O
over O
time O
. O

Interestingly O
, O
the O
size O
of O
the O
population O
appears O
to O
be O
correlated O
with O
the O
frequency O
of O
behavioral O
seizures O
, O
because O
animals O
with O
more O
ectopic O
granule O
cells O
in O
the O
hilus O
have O
more O
frequent O
behavioral O
seizures O
. O

The O
hilar O
ectopic O
granule O
cell O
population O
does O
not O
appear O
to O
vary O
systematically O
across O
the O
septotemporal O
axis O
, O
although O
it O
is O
associated O
with O
an O
increase O
in O
volume O
of O
the O
hilus O
. O

The O
results O
provide O
new O
insight O
into O
the O
potential O
role O
of O
ectopic O
hilar O
granule O
cells O
in O
the O
pilocarpine B
model O
of O
temporal O
lobe O
epilepsy O
. O

A O
prospective O
, O
open O
- O
label O
trial O
of O
galantamine B
in O
autistic O
disorder O
. O

OBJECTIVE O
: O
Post O
- O
mortem O
studies O
have O
reported O
abnormalities O
of O
the O
cholinergic O
system O
in O
autism O
. O

The O
purpose O
of O
this O
study O
was O
to O
assess O
the O
use O
of O
galantamine B
, O
an O
acetylcholinesterase O
inhibitor O
and O
nicotinic O
receptor O
modulator O
, O
in O
the O
treatment O
of O
interfering O
behaviors O
in O
children O
with O
autism O
. O

METHODS O
: O
Thirteen O
medication O
- O
free O
children O
with O
autism O
( O
mean O
age O
, O
8 O
. O
8 O
+ O
/ O
- O
3 O
. O
5 O
years O
) O
participated O
in O
a O
12 O
- O
week O
, O
open O
- O
label O
trial O
of O
galantamine B
. O

Patients O
were O
rated O
monthly O
by O
parents O
on O
the O
Aberrant O
Behavior O
Checklist O
( O
ABC O
) O
and O
the O
Conners O
' O
Parent O
Rating O
Scale O
- O
Revised O
, O
and O
by O
a O
physician O
using O
the O
Children O
' O
s O
Psychiatric O
Rating O
Scale O
and O
the O
Clinical O
Global O
Impressions O
scale O
. O

RESULTS O
: O
Patients O
showed O
a O
significant O
reduction O
in O
parent O
- O
rated O
irritability O
and O
social O
withdrawal O
on O
the O
ABC O
as O
well O
as O
significant O
improvements O
in O
emotional O
lability O
and O
inattention O
on O
the O
Conners O
' O
Parent O
Rating O
Scale O
- O
- O
Revised O
. O

Similarly O
, O
clinician O
ratings O
showed O
reductions O
in O
the O
anger O
subscale O
of O
the O
Children O
' O
s O
Psychiatric O
Rating O
Scale O
. O

Eight O
of O
13 O
participants O
were O
rated O
as O
responders O
on O
the O
basis O
of O
their O
improvement O
scores O
on O
the O
Clinical O
Global O
Impressions O
scale O
. O

Overall O
, O
galantamine B
was O
well O
- O
tolerated O
, O
with O
no O
significant O
adverse O
effects O
apart O
from O
headaches O
in O
one O
patient O
. O

CONCLUSION O
: O
In O
this O
open O
trial O
, O
galantamine B
was O
well O
- O
tolerated O
and O
appeared O
to O
be O
beneficial O
for O
the O
treatment O
of O
interfering O
behaviors O
in O
children O
with O
autism O
, O
particularly O
aggression O
, O
behavioral O
dyscontrol O
, O
and O
inattention O
. O

Further O
controlled O
trials O
are O
warranted O
. O

Randomized O
comparison O
of O
olanzapine B
versus O
risperidone B
for O
the O
treatment O
of O
first O
- O
episode O
schizophrenia O
: O
4 O
- O
month O
outcomes O
. O

OBJECTIVE O
: O
The O
authors O
compared O
4 O
- O
month O
treatment O
outcomes O
for O
olanzapine B
versus O
risperidone B
in O
patients O
with O
first O
- O
episode O
schizophrenia O
spectrum O
disorders O
. O

METHOD O
: O
One O
hundred O
twelve O
subjects O
( O
70 O
% O
male O
; O
mean O
age O
= O
23 O
. O
3 O
years O
[ O
SD O
= O
5 O
. O
1 O
] O
) O
with O
first O
- O
episode O
schizophrenia O
( O
75 O
% O
) O
, O
schizophreniform O
disorder O
( O
17 O
% O
) O
, O
or O
schizoaffective O
disorder O
( O
8 O
% O
) O
were O
randomly O
assigned O
to O
treatment O
with O
olanzapine B
( O
2 O
. O
5 O
- O
20 O
mg O
/ O
day O
) O
or O
risperidone B
( O
1 O
- O
6 O
mg O
/ O
day O
) O
. O

RESULTS O
: O
Response O
rates O
did O
not O
significantly O
differ O
between O
olanzapine B
( O
43 O
. O
7 O
% O
, O
95 O
% O
CI O
= O
28 O
. O
8 O
% O
- O
58 O
. O
6 O
% O
) O
and O
risperidone B
( O
54 O
. O
3 O
% O
, O
95 O
% O
CI O
= O
39 O
. O
9 O
% O
- O
68 O
. O
7 O
% O
) O
. O

Among O
those O
responding O
to O
treatment O
, O
more O
subjects O
in O
the O
olanzapine B
group O
( O
40 O
. O
9 O
% O
, O
95 O
% O
CI O
= O
16 O
. O
8 O
% O
- O
65 O
. O
0 O
% O
) O
than O
in O
the O
risperidone B
group O
( O
18 O
. O
9 O
% O
, O
95 O
% O
CI O
= O
0 O
% O
- O
39 O
. O
2 O
% O
) O
had O
subsequent O
ratings O
not O
meeting O
response O
criteria O
. O

Negative O
symptom O
outcomes O
and O
measures O
of O
parkinsonism O
and O
akathisia O
did O
not O
differ O
between O
medications O
. O

Extrapyramidal O
symptom O
severity O
scores O
were O
1 O
. O
4 O
( O
95 O
% O
CI O
= O
1 O
. O
2 O
- O
1 O
. O
6 O
) O
with O
risperidone B
and O
1 O
. O
2 O
( O
95 O
% O
CI O
= O
1 O
. O
0 O
- O
1 O
. O
4 O
) O
with O
olanzapine B
. O

Significantly O
more O
weight O
gain O
occurred O
with O
olanzapine B
than O
with O
risperidone B
: O
the O
increase O
in O
weight O
at O
4 O
months O
relative O
to O
baseline O
weight O
was O
17 O
. O
3 O
% O
( O
95 O
% O
CI O
= O
14 O
. O
2 O
% O
- O
20 O
. O
5 O
% O
) O
with O
olanzapine B
and O
11 O
. O
3 O
% O
( O
95 O
% O
CI O
= O
8 O
. O
4 O
% O
- O
14 O
. O
3 O
% O
) O
with O
risperidone B
. O

Body O
mass O
index O
at O
baseline O
and O
at O
4 O
months O
was O
24 O
. O
3 O
( O
95 O
% O
CI O
= O
22 O
. O
8 O
- O
25 O
. O
7 O
) O
versus O
28 O
. O
2 O
( O
95 O
% O
CI O
= O
26 O
. O
7 O
- O
29 O
. O
7 O
) O
with O
olanzapine B
and O
23 O
. O
9 O
( O
95 O
% O
CI O
= O
22 O
. O
5 O
- O
25 O
. O
3 O
) O
versus O
26 O
. O
7 O
( O
95 O
% O
CI O
= O
25 O
. O
2 O
- O
28 O
. O
2 O
) O
with O
risperidone B
. O

CONCLUSIONS O
: O
Clinical O
outcomes O
with O
risperidone B
were O
equal O
to O
those O
with O
olanzapine B
, O
and O
response O
may O
be O
more O
stable O
. O

Olanzapine B
may O
have O
an O
advantage O
for O
motor O
side O
effects O
. O

Both O
medications O
caused O
substantial O
rapid O
weight O
gain O
, O
but O
weight O
gain O
was O
greater O
with O
olanzapine B
. O

Early O
paracentral O
visual O
field O
loss O
in O
patients O
taking O
hydroxychloroquine B
. O

OBJECTIVE O
: O
To O
review O
the O
natural O
history O
and O
ocular O
and O
systemic O
adverse O
effects O
of O
patients O
taking O
hydroxychloroquine B
sulfate I
who O
attended O
an O
ophthalmic O
screening O
program O
. O

DESIGN O
: O
Retrospective O
study O
. O

RESULTS O
: O
Records O
of O
262 O
patients O
who O
were O
taking O
hydroxychloroquine B
and O
screened O
in O
the O
Department O
of O
Ophthalmology O
were O
reviewed O
. O

Of O
the O
262 O
patients O
, O
14 O
( O
18 O
% O
) O
of O
76 O
who O
had O
stopped O
treatment O
at O
the O
time O
of O
the O
study O
experienced O
documented O
adverse O
effects O
. O

Systemic O
adverse O
effects O
occurred O
in O
8 O
patients O
( O
10 O
. O
5 O
% O
) O
and O
ocular O
adverse O
effects O
, O
in O
5 O
( O
6 O
. O
5 O
% O
) O
. O

Thirty O
- O
five O
patients O
( O
13 O
. O
4 O
% O
) O
had O
visual O
field O
abnormalities O
, O
which O
were O
attributed O
to O
hydroxychloroquine B
treatment O
in O
4 O
patients O
( O
1 O
. O
5 O
% O
) O
. O

Three O
of O
the O
4 O
patients O
were O
taking O
less O
than O
6 O
. O
5 O
mg O
/ O
kg O
per O
day O
and O
all O
patients O
had O
normal O
renal O
and O
liver O
function O
test O
results O
. O

CONCLUSIONS O
: O
The O
current O
study O
used O
a O
protocol O
of O
visual O
acuity O
and O
color O
vision O
assessment O
, O
funduscopy O
, O
and O
Humphrey O
10 O
- O
2 O
visual O
field O
testing O
and O
shows O
that O
visual O
field O
defects O
appeared O
before O
any O
corresponding O
changes O
in O
any O
other O
tested O
clinical O
parameters O
; O
the O
defects O
were O
reproducible O
and O
the O
test O
parameters O
were O
reliable O
. O

Patients O
taking O
hydroxychloroquine B
can O
demonstrate O
a O
toxic O
reaction O
in O
the O
retina O
despite O
the O
absence O
of O
known O
risk O
factors O
. O

Screening O
, O
including O
Humphrey O
10 O
- O
2 O
visual O
field O
assessment O
, O
is O
recommended O
2 O
years O
after O
the O
initial O
baseline O
and O
yearly O
thereafter O
. O

Peri O
- O
operative O
atrioventricular O
block O
as O
a O
result O
of O
chemotherapy O
with O
epirubicin B
and O
paclitaxel B
. O

A O
47 O
- O
year O
- O
old O
woman O
presented O
for O
mastectomy O
and O
immediate O
latissimus O
dorsi O
flap O
reconstruction O
having O
been O
diagnosed O
with O
carcinoma O
of O
the O
breast O
6 O
months O
previously O
. O

In O
the O
preceding O
months O
she O
had O
received O
neo O
- O
adjuvant O
chemotherapy O
with O
epirubicin B
, O
paclitaxel B
( O
Taxol B
) O
and O
cyclophosphamide B
. O

This O
had O
been O
apparently O
uncomplicated O
and O
she O
had O
maintained O
a O
remarkably O
high O
level O
of O
physical O
activity O
. O

She O
was O
found O
to O
be O
bradycardic O
at O
pre O
- O
operative O
assessment O
but O
had O
no O
cardiac O
symptoms O
. O

Second O
degree O
Mobitz O
type O
II O
atrioventricular O
block O
was O
diagnosed O
on O
electrocardiogram O
, O
and O
temporary O
transvenous O
ventricular O
pacing O
instituted O
in O
the O
peri O
- O
operative O
period O
. O

We O
discuss O
how O
evidence O
- O
based O
guidelines O
would O
not O
have O
been O
helpful O
in O
this O
case O
, O
and O
how O
chemotherapy O
can O
exhibit O
substantial O
cardiotoxicity O
that O
may O
develop O
over O
many O
years O
. O

We O
suggest O
that O
patients O
who O
have O
received O
chemotherapy O
at O
any O
time O
should O
have O
a O
pre O
- O
operative O
electrocardiogram O
even O
if O
they O
are O
asymptomatic O
. O

Risks O
and O
benefits O
of O
COX O
- O
2 O
inhibitors O
vs O
non O
- O
selective O
NSAIDs O
: O
does O
their O
cardiovascular O
risk O
exceed O
their O
gastrointestinal O
benefit O
? O

A O
retrospective O
cohort O
study O
. O

OBJECTIVES O
: O
The O
risk O
of O
acute O
myocardial O
infarction O
( O
AMI O
) O
with O
COX O
- O
2 O
inhibitors O
may O
offset O
their O
gastrointestinal O
( O
GI O
) O
benefit O
compared O
with O
non O
- O
selective O
( O
NS O
) O
non O
- O
steroidal O
anti O
- O
inflammatory O
drugs O
( O
NSAIDs O
) O
. O

We O
aimed O
to O
compare O
the O
risks O
of O
hospitalization O
for O
AMI O
and O
GI O
bleeding O
among O
elderly O
patients O
using O
COX O
- O
2 O
inhibitors O
, O
NS O
- O
NSAIDs O
and O
acetaminophen B
. O

METHODS O
: O
We O
conducted O
a O
retrospective O
cohort O
study O
using O
administrative O
data O
of O
patients O
> O
or O
= O
65 O
years O
of O
age O
who O
filled O
a O
prescription O
for O
NSAID O
or O
acetaminophen B
during O
1999 O
- O
2002 O
. O

Outcomes O
were O
compared O
using O
Cox O
regression O
models O
with O
time O
- O
dependent O
exposures O
. O

RESULTS O
: O
Person O
- O
years O
of O
exposure O
among O
non O
- O
users O
of O
aspirin B
were O
: O
75 O
, O
761 O
to O
acetaminophen B
, O
42 O
, O
671 O
to O
rofecoxib B
65 O
, O
860 O
to O
celecoxib B
, O
and O
37 O
, O
495 O
to O
NS O
- O
NSAIDs O
. O

Among O
users O
of O
aspirin B
, O
they O
were O
: O
14 O
, O
671 O
to O
rofecoxib B
, O
22 O
, O
875 O
to O
celecoxib B
, O
9 O
, O
832 O
to O
NS O
- O
NSAIDs O
and O
38 O
, O
048 O
to O
acetaminophen B
. O

Among O
non O
- O
users O
of O
aspirin B
, O
the O
adjusted O
hazard O
ratios O
( O
95 O
% O
confidence O
interval O
) O
of O
hospitalization O
for O
AMI O
/ O
GI O
vs O
the O
acetaminophen B
( O
with O
no O
aspirin B
) O
group O
were O
: O
rofecoxib B
1 O
. O
27 O
( O
1 O
. O
13 O
, O
1 O
. O
42 O
) O
, O
celecoxib B
0 O
. O
93 O
( O
0 O
. O
83 O
, O
1 O
. O
03 O
) O
, O
naproxen B
1 O
. O
59 O
( O
1 O
. O
31 O
, O
1 O
. O
93 O
) O
, O
diclofenac B
1 O
. O
17 O
( O
0 O
. O
99 O
, O
1 O
. O
38 O
) O
and O
ibuprofen B
1 O
. O
05 O
( O
0 O
. O

74 O
, O
1 O
. O
51 O
) O
. O

Among O
users O
of O
aspirin B
, O
they O
were O
: O
rofecoxib B
1 O
. O
73 O
( O
1 O
. O
52 O
, O
1 O
. O
98 O
) O
, O
celecoxib B
1 O
. O
34 O
( O
1 O
. O
19 O
, O
1 O
. O
52 O
) O
, O
ibuprofen B
1 O
. O
51 O
( O
0 O
. O
95 O
, O
2 O
. O
41 O
) O
, O
diclofenac B
1 O
. O
69 O
( O
1 O
. O
35 O
, O
2 O
. O
10 O
) O
, O
naproxen B
1 O
. O
35 O
( O
0 O
. O
97 O
, O
1 O
. O
88 O
) O
and O
acetaminophen B
1 O
. O
29 O
( O
1 O
. O
17 O
, O
1 O
. O
42 O
) O
. O

CONCLUSION O
: O
Among O
non O
- O
users O
of O
aspirin B
, O
naproxen B
seemed O
to O
carry O
the O
highest O
risk O
for O
AMI O
/ O
GI O
bleeding O
. O

The O
AMI B
/ O
GI O
toxicity O
of O
celecoxib B
was O
similar O
to O
that O
of O
acetaminophen B
and O
seemed O
to O
be O
better O
than O
those O
of O
rofecoxib B
and O
NS O
- O
NSAIDs O
. O

Among O
users O
of O
aspirin B
, O
both O
celecoxib B
and O
naproxen B
seemed O
to O
be O
the O
least O
toxic O
. O

Quinine B
- O
induced O
arrhythmia O
in O
a O
patient O
with O
severe O
malaria O
. O

It O
was O
reported O
that O
there O
was O
a O
case O
of O
severe O
malaria O
patient O
with O
jaundice O
who O
presented O
with O
arrhythmia O
( O
premature O
ventricular O
contraction O
) O
while O
getting O
quinine B
infusion O
was O
reported O
. O

A O
man O
, O
25 O
years O
old O
, O
was O
admitted O
to O
hospital O
with O
high O
fever O
, O
chill O
, O
vomiting O
, O
jaundice O
. O

The O
patient O
was O
fully O
conscious O
, O
blood O
pressure O
120 O
/ O
80 O
mmHg O
, O
pulse O
rate O
100 O
x O
/ O
minute O
, O
regular O
. O

On O
admission O
, O
laboratory O
examination O
showed O
Plasmodium O
falciparum O
( O
+ O
+ O
+ O
+ O
) O
, O
total O
bilirubin B
8 O
. O
25 O
mg O
/ O
dL O
, O
conjugated O
bilirubin B
4 O
. O
36 O
mg O
/ O
dL O
, O
unconjugated O
bilirubin B
3 O
. O
89 O
mg O
/ O
dL O
, O
potassium B
3 O
. O
52 O
meq O
/ O
L O
Patient O
was O
diagnosed O
as O
severe O
malaria O
with O
jaundice O
and O
got O
quinine B
infusion O
in O
dextrose B
5 O
% O
500 O
mg O
/ O
8 O
hour O
. O

On O
the O
second O
day O
the O
patient O
had O
vomitus O
, O
diarrhea O
, O
tinnitus O
, O
loss O
of O
hearing O
. O

After O
30 O
hours O
of O
quinine B
infusion O
the O
patient O
felt O
palpitation O
and O
electrocardiography O
( O
ECG O
) O
recording O
showed O
premature O
ventricular O
contraction O
( O
PVC O
) O
> O
5 O
x O
/ O
minute O
, O
trigemini O
, O
constant O
type O
- O
- O
sinoatrial O
block O
, O
positive O
U O
wave O
. O

He O
was O
treated O
with O
lidocaine B
50 O
mg O
intravenously O
followed O
by O
infusion O
1500 O
mg O
in O
dextrose B
5 O
% O
/ O
24 O
hour O
and O
potassium B
aspartate I
tablet O
. O

Quinine B
infusion O
was O
discontinued O
and O
changed O
with O
sulfate O
quinine B
tablets O
. O

Three O
hours O
later O
the O
patient O
felt O
better O
, O
the O
frequency O
of O
PVC O
reduced O
to O
4 O
- O
5 O
x O
/ O
minute O
and O
on O
the O
third O
day O
ECG O
was O
normal O
, O
potassium B
level O
was O
3 O
. O
34 O
meq O
/ O
L O
. O

He O
was O
discharged O
on O
7th O
day O
in O
good O
condition O
. O

Quinine B
, O
like O
quinidine B
, O
is O
a O
chincona O
alkaloid O
that O
has O
anti O
- O
arrhythmic O
property O
, O
although O
it O
also O
pro O
- O
arrhythmic O
that O
can O
cause O
various O
arrhythmias O
, O
including O
severe O
arrhythmia O
such O
as O
multiple O
PVC O
. O

Administration O
of O
parenteral O
quinine B
must O
be O
done O
carefully O
and O
with O
good O
observation O
because O
of O
its O
pro O
- O
arrhythmic O
effect O
, O
especially O
in O
older O
patients O
who O
have O
heart O
diseases O
or O
patients O
with O
electrolyte O
disorder O
( O
hypokalemia O
) O
which O
frequently O
occurs O
due O
to O
vomiting O
and O
or O
diarrhea O
in O
malaria O
cases O
. O

Penicillamine B
- O
related O
lichenoid O
dermatitis O
and O
utility O
of O
zinc B
acetate I
in O
a O
Wilson O
disease O
patient O
with O
hepatic O
presentation O
, O
anxiety O
and O
SPECT O
abnormalities O
. O

Wilson O
' O
s O
disease O
is O
an O
autosomal O
recessive O
disorder O
of O
hepatic O
copper B
metabolism O
with O
consequent O
copper B
accumulation O
and O
toxicity O
in O
many O
tissues O
and O
consequent O
hepatic O
, O
neurologic O
and O
psychiatric O
disorders O
. O

We O
report O
a O
case O
of O
Wilson O
' O
s O
disease O
with O
chronic O
liver O
disease O
; O
moreover O
, O
in O
our O
patient O
, O
presenting O
also O
with O
high O
levels O
of O
state O
anxiety O
without O
depression O
, O
99mTc O
- O
ECD O
- O
SPECT O
showed O
cortical O
hypoperfusion O
in O
frontal O
lobes O
, O
more O
marked O
on O
the O
left O
frontal O
lobe O
. O

During O
the O
follow O
- O
up O
of O
our O
patient O
, O
penicillamine B
was O
interrupted O
after O
the O
appearance O
of O
a O
lichenoid O
dermatitis O
, O
and O
zinc B
acetate I
permitted O
to O
continue O
the O
successful O
treatment O
of O
the O
patient O
without O
side O
- O
effects O
. O

In O
our O
case O
the O
therapy O
with O
zinc B
acetate I
represented O
an O
effective O
treatment O
for O
a O
Wilson O
' O
s O
disease O
patient O
in O
which O
penicillamine B
- O
related O
side O
effects O
appeared O
. O

The O
safety O
of O
the O
zinc B
acetate I
allowed O
us O
to O
avoid O
other O
potentially O
toxic O
chelating O
drugs O
; O
this O
observation O
is O
in O
line O
with O
the O
growing O
evidence O
on O
the O
efficacy O
of O
the O
drug O
in O
the O
treatment O
of O
Wilson O
' O
s O
disease O
. O

Since O
most O
of O
Wilson O
' O
s O
disease O
penicillamine B
- O
treated O
patients O
do O
not O
seem O
to O
develop O
this O
skin O
lesion O
, O
it O
could O
be O
conceivable O
that O
a O
specific O
genetic O
factor O
is O
involved O
in O
drug O
response O
. O

Further O
studies O
are O
needed O
for O
a O
better O
clarification O
of O
Wilson O
' O
s O
disease O
therapy O
, O
and O
in O
particular O
to O
differentiate O
specific O
therapies O
for O
different O
Wilson O
' O
s O
disease O
phenotypes O
. O

A O
dramatic O
drop O
in O
blood O
pressure O
following O
prehospital O
GTN B
administration O
. O

A O
male O
in O
his O
sixties O
with O
no O
history O
of O
cardiac O
chest O
pain O
awoke O
with O
chest O
pain O
following O
an O
afternoon O
sleep O
. O

The O
patient O
did O
not O
self O
medicate O
. O

The O
patient O
' O
s O
observations O
were O
within O
normal O
limits O
, O
he O
was O
administered O
oxygen B
via O
a O
face O
mask O
and O
glyceryl B
trinitrate I
( O
GTN B
) O
. O

Several O
minutes O
after O
the O
GTN B
the O
patient O
experienced O
a O
sudden O
drop O
in O
blood O
pressure O
and O
heart O
rate O
, O
this O
was O
rectified O
by O
atropine B
sulphate I
and O
a O
fluid O
challenge O
. O

There O
was O
no O
further O
deterioration O
in O
the O
patient O
' O
s O
condition O
during O
transport O
to O
hospital O
. O

There O
are O
very O
few O
documented O
case O
like O
this O
in O
the O
prehospital O
scientific O
literature O
. O

The O
cause O
appears O
to O
be O
the O
Bezold O
- O
Jarish O
reflex O
, O
stimulation O
of O
the O
ventricular O
walls O
which O
in O
turn O
decreases O
sympathetic O
outflow O
from O
the O
vasomotor O
centre O
. O

Prehospital O
care O
providers O
who O
are O
managing O
any O
patient O
with O
a O
syncopal O
episode O
that O
fails O
to O
recover O
within O
a O
reasonable O
time O
frame O
should O
consider O
the O
Bezold O
- O
Jarisch O
reflex O
as O
the O
cause O
and O
manage O
the O
patient O
accordingly O
. O

Chronic O
lesion O
of O
rostral O
ventrolateral O
medulla O
in O
spontaneously O
hypertensive O
rats O
. O

We O
studied O
the O
effects O
of O
chronic O
selective O
neuronal O
lesion O
of O
rostral O
ventrolateral O
medulla O
on O
mean O
arterial O
pressure O
, O
heart O
rate O
, O
and O
neurogenic O
tone O
in O
conscious O
, O
unrestrained O
spontaneously O
hypertensive O
rats O
. O

The O
lesions O
were O
placed O
via O
bilateral O
microinjections O
of O
30 O
nmol O
/ O
200 O
nl O
N B
- I
methyl I
- I
D I
- I
aspartic I
acid I
. O

The O
restimulation O
of O
this O
area O
with O
N B
- I
methyl I
- I
D I
- I
aspartic I
acid I
15 O
days O
postlesion O
failed O
to O
produce O
a O
pressor O
response O
. O

One O
day O
postlesion O
, O
the O
resting O
mean O
arterial O
pressure O
was O
significantly O
decreased O
in O
lesioned O
rats O
when O
compared O
with O
sham O
rats O
( O
100 O
+ O
/ O
- O
7 O
versus O
173 O
+ O
/ O
- O
4 O
mm O
Hg O
, O
p O
less O
than O
0 O
. O
05 O
) O
. O

Fifteen O
days O
later O
, O
the O
lesioned O
group O
still O
showed O
values O
significantly O
lower O
than O
the O
sham O
group O
( O
150 O
+ O
/ O
- O
6 O
versus O
167 O
+ O
/ O
- O
5 O
mm O
Hg O
, O
p O
less O
than O
0 O
. O
05 O
) O
. O

No O
significant O
heart O
rate O
differences O
were O
observed O
between O
the O
sham O
and O
lesioned O
groups O
. O

The O
ganglionic O
blocker O
trimethaphan B
( O
5 O
mg O
/ O
kg O
i O
. O
v O
. O
) O
caused O
similar O
reductions O
in O
mean O
arterial O
pressure O
in O
both O
lesioned O
and O
sham O
groups O
. O

The O
trimethaphan B
- O
induced O
hypotension O
was O
accompanied O
by O
a O
significant O
bradycardia O
in O
lesioned O
rats O
( O
- O
32 O
+ O
/ O
- O
13 O
beats O
per O
minute O
) O
but O
a O
tachycardia O
in O
sham O
rats O
( O
+ O
33 O
+ O
/ O
- O
12 O
beats O
per O
minute O
) O
1 O
day O
postlesion O
. O

Therefore O
, O
rostral O
ventrolateral O
medulla O
neurons O
appear O
to O
play O
a O
significant O
role O
in O
maintaining O
hypertension O
in O
conscious O
spontaneously O
hypertensive O
rats O
. O

Spinal O
or O
suprabulbar O
structures O
could O
be O
responsible O
for O
the O
gradual O
recovery O
of O
the O
hypertension O
in O
the O
lesioned O
rats O
. O

Acute O
encephalopathy O
and O
cerebral O
vasospasm O
after O
multiagent O
chemotherapy O
including O
PEG B
- I
asparaginase I
and O
intrathecal O
cytarabine B
for O
the O
treatment O
of O
acute O
lymphoblastic O
leukemia O
. O

A O
7 O
- O
year O
- O
old O
girl O
with O
an O
unusual O
reaction O
to O
induction O
chemotherapy O
for O
precursor O
B O
- O
cell O
acute O
lymphoblastic O
leukemia O
( O
ALL O
) O
is O
described O
. O

The O
patient O
developed O
acute O
encephalopathy O
evidenced O
by O
behavioral O
changes O
, O
aphasia O
, O
incontinence O
, O
visual O
hallucinations O
, O
and O
right O
- O
sided O
weakness O
with O
diffuse O
cerebral O
vasospasm O
on O
magnetic O
resonance O
angiography O
after O
the O
administration O
of O
intrathecal O
cytarabine B
. O

Vincristine B
, O
dexamethasone B
, O
and O
polyethylene B
glycol I
- O
asparaginase B
were O
also O
administered O
before O
the O
episode O
as O
part O
of O
induction O
therapy O
. O

Neurologic O
status O
returned O
to O
baseline O
within O
10 O
days O
of O
the O
acute O
event O
, O
and O
magnetic O
resonance O
angiography O
findings O
returned O
to O
normal O
4 O
months O
later O
. O

Comparison O
of O
valsartan B
/ O
hydrochlorothiazide B
combination O
therapy O
at O
doses O
up O
to O
320 O
/ O
25 O
mg O
versus O
monotherapy O
: O
a O
double O
- O
blind O
, O
placebo O
- O
controlled O
study O
followed O
by O
long O
- O
term O
combination O
therapy O
in O
hypertensive O
adults O
. O

BACKGROUND O
: O
One O
third O
of O
patients O
treated O
for O
hypertension O
attain O
adequate O
blood O
pressure O
( O
BP O
) O
control O
, O
and O
multidrug O
regimens O
are O
often O
required O
. O

Given O
the O
lifelong O
nature O
of O
hypertension O
, O
there O
is O
a O
need O
to O
evaluate O
the O
long O
- O
term O
efficacy O
and O
tolerability O
of O
higher O
doses O
of O
combination O
anti O
- O
hypertensive O
therapies O
. O

OBJECTIVE O
: O
This O
study O
investigated O
the O
efficacy O
and O
tolerability O
of O
valsartan B
( O
VAL B
) O
or O
hydrochlorothiazide B
( O
HCTZ B
) O
- O
monotherapy O
and O
higher O
- O
dose O
combinations O
in O
patients O
with O
essential O
hypertension O
. O

METHODS O
: O
The O
first O
part O
of O
this O
study O
was O
an O
8 O
- O
week O
, O
multicenter O
, O
randomized O
, O
double O
- O
blind O
, O
placebo O
controlled O
, O
parallel O
- O
group O
trial O
. O

Patients O
with O
essential O
hypertension O
( O
mean O
sitting O
diastolic O
BP O
[ O
MSDBP O
] O
, O
> O
or O
= O
95 O
mm O
Hg O
and O
< O
110 O
mm O
Hg O
) O
were O
randomized O
to O
1 O
of O
8 O
treatment O
groups O
: O
VAL B
160 O
or O
320 O
mg O
; O
HCTZ B
12 O
. O
5 O
or O
25 O
mg O
; O
VAL B
/ O
HCTZ B
160 O
/ O
12 O
. O
5 O
, O
320 O
/ O
12 O
. O
5 O
, O
or O
320 O
/ O
25 O
mg O
; O
or O
placebo O
. O

Mean O
changes O
in O
MSDBP O
and O
mean O
sitting O
systolic O
BP O
( O
MSSBP O
) O
were O
analyzed O
at O
the O
8 O
- O
week O
core O
study O
end O
point O
. O

VAL B
/ O
HCTZ B
320 O
/ O
12 O
. O
5 O
and O
320 O
/ O
25 O
mg O
were O
further O
investigated O
in O
a O
54 O
- O
week O
, O
open O
- O
label O
extension O
. O

Response O
was O
defined O
as O
MSDBP O
< O
90 O
mm O
Hg O
or O
a O
> O
or O
= O
10 O
mm O
Hg O
decrease O
compared O
to O
baseline O
. O

Control O
was O
defined O
as O
MSDBP O
< O
90 O
mm O
Hg O
compared O
with O
baseline O
. O

Tolerability O
was O
assessed O
by O
monitoring O
adverse O
events O
at O
randomization O
and O
all O
subsequent O
study O
visits O
and O
regular O
evaluation O
of O
hematology O
and O
blood O
chemistry O
. O

RESULTS O
: O
A O
total O
of O
1346 O
patients O
were O
randomized O
into O
the O
8 O
- O
week O
core O
study O
( O
734 O
men O
, O
612 O
women O
; O
924 O
white O
, O
291 O
black O
, O
23 O
Asian O
, O
108 O
other O
; O
mean O
age O
, O
52 O
. O
7 O
years O
; O
mean O
weight O
, O
92 O
. O
6 O
kg O
) O
. O

All O
active O
treatments O
were O
associated O
with O
significantly O
reduced O
MSSBP O
and O
MSDBP O
during O
the O
core O
8 O
- O
week O
study O
, O
with O
each O
monotherapy O
significantly O
contributing O
to O
the O
overall O
effect O
of O
combination O
therapy O
( O
VAL B
and O
HCTZ B
, O
P O
< O
0 O
. O
001 O
) O
. O

Each O
combination O
was O
associated O
with O
significantly O
greater O
reductions O
in O
MSSBP O
and O
MSDBP O
compared O
with O
the O
monotherapies O
and O
placebo O
( O
all O
, O
P O
< O
0 O
. O
001 O
) O
. O

The O
mean O
reduction O
in O
MSSBP O
/ O
MSDBP O
with O
VAL B
/ O
HCTZ B
320 O
/ O
25 O
mg O
was O
24 O
. O
7 O
/ O
16 O
. O
6 O
mm O
Hg O
, O
compared O
with O
5 O
. O
9 O
/ O
7 O
. O
0 O
mm O
Hg O
with O
placebo O
. O

The O
reduction O
in O
MSSBP O
was O
significantly O
greater O
with O
VAL B
/ O
HCTZ B
320 O
/ O
25 O
mg O
compared O
with O
VAL B
/ O
HCTZ B
160 O
/ O
12 O
. O
5 O
mg O
( O
P O
< O
0 O
. O
002 O
) O
. O

Rates O
of O
response O
and O
BP O
control O
were O
significantly O
higher O
in O
the O
groups O
that O
received O
combination O
treatment O
compared O
with O
those O
that O
received O
monotherapy O
. O

The O
incidence O
of O
hypokalemia O
was O
lower O
with O
VAL B
/ O
HCTZ B
combinations O
( O
1 O
. O
8 O
% O
- O
6 O
. O
1 O
% O
) O
than O
with O
HCTZ B
monotherapies O
( O
7 O
. O
1 O
% O
- O
13 O
. O
3 O
% O
) O
. O

The O
majority O
of O
adverse O
events O
in O
the O
core O
study O
were O
of O
mild O
to O
moderate O
severity O
. O

The O
efficacy O
and O
tolerability O
of O
VAL B
/ O
HCTZ B
combinations O
were O
maintained O
during O
the O
extension O
( O
797 O
patients O
) O
. O

CONCLUSIONS O
: O
In O
this O
study O
population O
, O
combination O
therapies O
with O
VAL B
/ O
HCTZ B
were O
associated O
with O
significantly O
greater O
BP O
reductions O
compared O
with O
either O
monotherapy O
, O
were O
well O
tolerated O
, O
and O
were O
associated O
with O
less O
hypokalemia O
than O
HCTZ B
alone O
. O

Succimer B
chelation O
improves O
learning O
, O
attention O
, O
and O
arousal O
regulation O
in O
lead B
- O
exposed O
rats O
but O
produces O
lasting O
cognitive O
impairment O
in O
the O
absence O
of O
lead B
exposure O
. O

BACKGROUND O
: O
There O
is O
growing O
pressure O
for O
clinicians O
to O
prescribe O
chelation O
therapy O
at O
only O
slightly O
elevated O
blood O
lead B
levels O
. O

However O
, O
very O
few O
studies O
have O
evaluated O
whether O
chelation O
improves O
cognitive O
outcomes O
in O
Pb B
- O
exposed O
children O
, O
or O
whether O
these O
agents O
have O
adverse O
effects O
that O
may O
affect O
brain O
development O
in O
the O
absence O
of O
Pb B
exposure O
. O

OBJECTIVES O
: O
The O
present O
study O
was O
designed O
to O
answer O
these O
questions O
, O
using O
a O
rodent O
model O
of O
early O
childhood O
Pb B
exposure O
and O
treatment O
with O
succimer B
, O
a O
widely O
used O
chelating O
agent O
for O
the O
treatment O
of O
Pb B
poisoning O
. O

RESULTS O
: O
Pb B
exposure O
produced O
lasting O
impairments O
in O
learning O
, O
attention O
, O
inhibitory O
control O
, O
and O
arousal O
regulation O
, O
paralleling O
the O
areas O
of O
dysfunction O
seen O
in O
Pb B
- O
exposed O
children O
. O

Succimer B
treatment O
of O
the O
Pb B
- O
exposed O
rats O
significantly O
improved O
learning O
, O
attention O
, O
and O
arousal O
regulation O
, O
although O
the O
efficacy O
of O
the O
treatment O
varied O
as O
a O
function O
of O
the O
Pb B
exposure O
level O
and O
the O
specific O
functional O
deficit O
. O

In O
contrast O
, O
succimer B
treatment O
of O
rats O
not O
previously O
exposed O
to O
Pb B
produced O
lasting O
and O
pervasive O
cognitive O
and O
affective O
dysfunction O
comparable O
in O
magnitude O
to O
that O
produced O
by O
the O
higher O
Pb B
exposure O
regimen O
. O

CONCLUSIONS O
: O
These O
are O
the O
first O
data O
, O
to O
our O
knowledge O
, O
to O
show O
that O
treatment O
with O
any O
chelating O
agent O
can O
alleviate O
cognitive O
deficits O
due O
to O
Pb B
exposure O
. O

These O
findings O
suggest O
that O
it O
may O
be O
possible O
to O
identify O
a O
succimer B
treatment O
protocol O
that O
improves O
cognitive O
outcomes O
in O
Pb B
- O
exposed O
children O
. O

However O
, O
they O
also O
suggest O
that O
succimer B
treatment O
should O
be O
strongly O
discouraged O
for O
children O
who O
do O
not O
have O
elevated O
tissue O
levels O
of O
Pb B
or O
other O
heavy O
metals B
. O

Caffeine B
challenge O
test O
in O
panic O
disorder O
and O
depression O
with O
panic O
attacks O
. O

Our O
aim O
was O
to O
observe O
if O
patients O
with O
panic O
disorder O
( O
PD O
) O
and O
patients O
with O
major O
depression O
with O
panic O
attacks O
( O
MDP O
) O
( O
Diagnostic O
and O
Statistical O
Manual O
of O
Mental O
Disorders O
, O
Fourth O
Edition O
criteria O
) O
respond O
in O
a O
similar O
way O
to O
the O
induction O
of O
panic O
attacks O
by O
an O
oral O
caffeine B
challenge O
test O
. O

We O
randomly O
selected O
29 O
patients O
with O
PD O
, O
27 O
with O
MDP O
, O
25 O
with O
major O
depression O
without O
panic O
attacks O
( O
MD O
) O
, O
and O
28 O
healthy O
volunteers O
. O

The O
patients O
had O
no O
psychotropic O
drug O
for O
at O
least O
a O
4 O
- O
week O
period O
. O

In O
a O
randomized O
double O
- O
blind O
experiment O
performed O
in O
2 O
occasions O
7 O
days O
apart O
, O
480 O
mg O
caffeine B
and O
a O
caffeine B
- O
free O
( O
placebo O
) O
solution O
were O
administered O
in O
a O
coffee O
form O
and O
anxiety O
scales O
were O
applied O
before O
and O
after O
each O
test O
. O

A O
total O
of O
58 O
. O
6 O
% O
( O
n O
= O
17 O
) O
of O
patients O
with O
PD O
, O
44 O
. O
4 O
% O
( O
n O
= O
12 O
) O
of O
patients O
with O
MDP O
, O
12 O
. O
0 O
% O
( O
n O
= O
3 O
) O
of O
patients O
with O
MD O
, O
and O
7 O
. O
1 O
% O
( O
n O
= O
2 O
) O
of O
control O
subjects O
had O
a O
panic O
attack O
after O
the O
480 O
- O
mg O
caffeine B
challenge O
test O
( O
chi O
( O
2 O
) O
( O
3 O
) O
= O
16 O
. O
22 O
, O
P O
= O
. O
001 O
) O
. O

The O
patients O
with O
PD O
and O
MDP O
were O
more O
sensitive O
to O
caffeine B
than O
were O
patients O
with O
MD O
and O
healthy O
volunteers O
. O

No O
panic O
attack O
was O
observed O
after O
the O
caffeine B
- O
free O
solution O
intake O
. O

The O
patients O
with O
MD O
had O
a O
lower O
heart O
rate O
response O
to O
the O
test O
than O
all O
the O
other O
groups O
( O
2 O
- O
way O
analysis O
of O
variance O
, O
group O
by O
time O
interaction O
with O
Greenhouse O
- O
Geisser O
correction O
: O
F O
( O
3 O
, O
762 O
) O
= O
2 O
. O
85 O
, O
P O
= O
. O
026 O
) O
. O

Our O
data O
suggest O
that O
there O
is O
an O
association O
between O
panic O
attacks O
, O
no O
matter O
if O
associated O
with O
PD O
or O
MDP O
, O
and O
hyperreactivity O
to O
an O
oral O
caffeine B
challenge O
test O
. O

Mitral O
annuloplasty O
as O
a O
ventricular O
restoration O
method O
for O
the O
failing O
left O
ventricle O
: O
a O
pilot O
study O
. O

BACKGROUND O
AND O
AIM O
OF O
THE O
STUDY O
: O
Undersized O
mitral O
annuloplasty O
( O
MAP O
) O
is O
effective O
in O
patients O
with O
dilated O
cardiomyopathy O
and O
functional O
mitral O
regurgitation O
( O
MR O
) O
since O
, O
as O
well O
as O
addressing O
the O
MR O
, O
the O
MAP O
may O
also O
reshape O
the O
dilated O
left O
ventricular O
( O
LV O
) O
base O
. O

However O
, O
the O
direct O
benefits O
of O
this O
possible O
reshaping O
on O
LV O
function O
in O
the O
absence O
of O
underlying O
MR O
remain O
incompletely O
understood O
. O

The O
study O
aim O
was O
to O
identify O
these O
benefits O
in O
a O
canine O
model O
of O
acute O
heart O
failure O
. O

METHODS O
: O
Six O
dogs O
underwent O
MAP O
with O
a O
prosthetic O
band O
on O
the O
posterior O
mitral O
annulus O
, O
using O
four O
mattress O
sutures O
. O

The O
sutures O
were O
passed O
individually O
through O
four O
tourniquets O
and O
exteriorized O
untied O
via O
the O
left O
atriotomy O
. O

Sonomicrometry O
crystals O
were O
implanted O
around O
the O
mitral O
annulus O
and O
left O
ventricle O
to O
measure O
geometry O
and O
regional O
function O
. O

Acute O
heart O
failure O
was O
induced O
by O
propranolol B
and O
volume O
loading O
after O
weaning O
from O
cardiopulmonary O
bypass O
; O
an O
absence O
of O
MR O
was O
confirmed O
by O
echocardiography O
. O

MAP O
was O
accomplished O
by O
cinching O
the O
tourniquets O
. O

Data O
were O
acquired O
at O
baseline O
, O
after O
induction O
of O
acute O
heart O
failure O
, O
and O
after O
MAP O
. O

RESULTS O
: O
MAP O
decreased O
mitral O
annular O
dimensions O
in O
both O
commissure O
- O
commissure O
and O
septal O
- O
lateral O
directions O
. O

Concomitantly O
, O
the O
diastolic O
diameter O
of O
the O
LV O
base O
and O
LV O
sphericity O
decreased O
( O
i O
. O
e O
. O
, O
improved O
) O
from O
37 O
. O
4 O
+ O
/ O
- O
9 O
. O
3 O
to O
35 O
. O
9 O
+ O
/ O
- O
10 O
mm O
( O
p O
= O
0 O
. O
063 O
) O
, O
and O
from O
67 O
. O
9 O
+ O
/ O
- O
18 O
. O
6 O
% O
to O
65 O
. O
3 O
+ O
/ O
- O
18 O
. O
9 O
% O
( O
p O
= O
0 O
. O
016 O
) O
, O
respectively O
. O

Decreases O
were O
evident O
in O
both O
LV O
end O
- O
diastolic O
pressure O
( O
from O
17 O
+ O
/ O
- O
7 O
to O
15 O
+ O
/ O
- O
6 O
mmHg O
, O
p O
= O
0 O
. O
0480 O
and O
Tau O
( O
from O
48 O
+ O
/ O
- O
8 O
to O
45 O
+ O
/ O
- O
8 O
ms O
, O
p O
< O
0 O
. O
01 O
) O
, O
while O
fractional O
shortening O
at O
the O
LV O
base O
increased O
from O
7 O
. O
7 O
+ O
/ O
- O
4 O
. O
5 O
% O
to O
9 O
. O
4 O
+ O
/ O
- O
4 O
. O
5 O
% O
( O
p O
= O
0 O
. O
045 O
) O
. O

After O
MAP O
, O
increases O
were O
identified O
in O
both O
cardiac O
output O
( O
from O
1 O
. O
54 O
+ O
/ O
- O
0 O
. O
57 O
to O
1 O
. O
65 O
+ O
/ O
- O
0 O
. O
57 O
1 O
/ O
min O
) O
and O
Emax O
( O
from O
1 O
. O
86 O
+ O
/ O
- O
0 O
. O
9 O
to O
2 O
. O
41 O
+ O
/ O
- O
1 O
. O
31 O
mmHg O
/ O
ml O
) O
. O

CONCLUSION O
: O
The O
data O
acquired O
suggest O
that O
isolated O
MAP O
may O
have O
certain O
benefits O
on O
LV O
dimension O
/ O
function O
in O
acute O
heart O
failure O
, O
even O
in O
the O
absence O
of O
MR O
. O

However O
, O
further O
investigations O
are O
warranted O
in O
a O
model O
of O
chronic O
heart O
failure O
. O

Piperacillin B
/ I
tazobactam I
- O
induced O
seizure O
rapidly O
reversed O
by O
high O
flux O
hemodialysis O
in O
a O
patient O
on O
peritoneal O
dialysis O
. O

Despite O
popular O
use O
of O
piperacillin B
, O
the O
dire O
neurotoxicity O
associated O
with O
piperacillin B
still O
goes O
unrecognized O
, O
leading O
to O
a O
delay O
in O
appropriate O
management O
. O

We O
report O
a O
57 O
- O
year O
- O
old O
woman O
with O
end O
- O
stage O
renal O
disease O
receiving O
continuous O
ambulatory O
peritoneal O
dialysis O
( O
CAPD O
) O
, O
who O
developed O
slurred O
speech O
, O
tremor O
, O
bizarre O
behavior O
, O
progressive O
mental O
confusion O
, O
and O
2 O
episodes O
of O
generalized O
tonic O
- O
clonic O
seizure O
( O
GTCS O
) O
after O
5 O
doses O
of O
piperacillin B
/ I
tazobactam I
( O
2 O
g O
/ O
250 O
mg O
) O
were O
given O
for O
bronchiectasis O
with O
secondary O
infection O
. O

The O
laboratory O
data O
revealed O
normal O
plasma O
electrolyte O
and O
ammonia B
levels O
but O
leukocytosis O
. O

Neurologic O
examinations O
showed O
dysarthria O
and O
bilateral O
Babinski O
sign O
. O

Computed O
tomography O
of O
brain O
and O
electroencephalogram O
were O
unremarkable O
. O

Despite O
the O
use O
of O
antiepileptic O
agents O
, O
another O
GTCS O
episode O
recurred O
after O
the O
sixth O
dose O
of O
piperacillin B
/ I
tazobactam I
. O

Brain O
magnetic O
resonance O
imaging O
did O
not O
demonstrate O
acute O
infarction O
and O
organic O
brain O
lesions O
. O

Initiation O
of O
high O
- O
flux O
hemodialysis O
rapidly O
reversed O
the O
neurologic O
symptoms O
within O
4 O
hours O
. O

Piperacillin B
- O
induced O
encephalopathy O
should O
be O
considered O
in O
any O
uremic O
patients O
with O
unexplained O
neurological O
manifestations O
. O

CAPD O
is O
inefficient O
in O
removing O
piperacillin B
, O
whereas O
hemodialysis O
can O
rapidly O
terminate O
the O
piperacillin B
- O
induced O
encephalopathy O
. O

Frequency O
of O
transient O
ipsilateral O
vocal O
cord O
paralysis O
in O
patients O
undergoing O
carotid O
endarterectomy O
under O
local O
anesthesia O
. O

BACKGROUND O
: O
Especially O
because O
of O
improvements O
in O
clinical O
neurologic O
monitoring O
, O
carotid O
endarterectomy O
done O
under O
local O
anesthesia O
has O
become O
the O
technique O
of O
choice O
in O
several O
centers O
. O

Temporary O
ipsilateral O
vocal O
nerve O
palsies O
due O
to O
local O
anesthetics O
have O
been O
described O
, O
however O
. O

Such O
complications O
are O
most O
important O
in O
situations O
where O
there O
is O
a O
pre O
- O
existing O
contralateral O
paralysis O
. O

We O
therefore O
examined O
the O
effect O
of O
local O
anesthesia O
on O
vocal O
cord O
function O
to O
better O
understand O
its O
possible O
consequences O
. O

METHODS O
: O
This O
prospective O
study O
included O
28 O
patients O
undergoing O
carotid O
endarterectomy O
under O
local O
anesthesia O
. O

Vocal O
cord O
function O
was O
evaluated O
before O
, O
during O
, O
and O
after O
surgery O
( O
postoperative O
day O
1 O
) O
using O
flexible O
laryngoscopy O
. O

Anesthesia O
was O
performed O
by O
injecting O
20 O
to O
40 O
mL O
of O
a O
mixture O
of O
long O
- O
acting O
( O
ropivacaine B
) O
and O
short O
- O
acting O
( O
prilocaine B
) O
anesthetic O
. O

RESULTS O
: O
All O
patients O
had O
normal O
vocal O
cord O
function O
preoperatively O
. O

Twelve O
patients O
( O
43 O
% O
) O
were O
found O
to O
have O
intraoperative O
ipsilateral O
vocal O
cord O
paralysis O
. O

It O
resolved O
in O
all O
cases O
< O
or O
= O
24 O
hours O
. O

There O
were O
no O
significant O
differences O
in O
operating O
time O
or O
volume O
or O
frequency O
of O
anesthetic O
administration O
in O
patients O
with O
temporary O
vocal O
cord O
paralysis O
compared O
with O
those O
without O
. O

CONCLUSION O
: O
Local O
anesthesia O
led O
to O
temporary O
ipsilateral O
vocal O
cord O
paralysis O
in O
almost O
half O
of O
these O
patients O
. O

Because O
pre O
- O
existing O
paralysis O
is O
of O
a O
relevant O
frequency O
( O
up O
to O
3 O
% O
) O
, O
a O
preoperative O
evaluation O
of O
vocal O
cord O
function O
before O
carotid O
endarterectomy O
under O
local O
anesthesia O
is O
recommended O
to O
avoid O
intraoperative O
bilateral O
paralysis O
. O

In O
patients O
with O
preoperative O
contralateral O
vocal O
cord O
paralysis O
, O
surgery O
under O
general O
anesthesia O
should O
be O
considered O
. O

Impaired O
fear O
recognition O
in O
regular O
recreational O
cocaine B
users O
. O

INTRODUCTION O
: O
The O
ability O
to O
read O
facial O
expressions O
is O
essential O
for O
normal O
human O
social O
interaction O
. O

The O
aim O
of O
the O
present O
study O
was O
to O
conduct O
the O
first O
investigation O
of O
facial O
expression O
recognition O
performance O
in O
recreational O
cocaine B
users O
. O

MATERIALS O
AND O
METHODS O
: O
Three O
groups O
, O
comprised O
of O
21 O
cocaine B
naive O
participants O
( O
CN O
) O
, O
30 O
occasional O
cocaine B
( O
OC B
) O
, O
and O
48 O
regular O
recreational O
cocaine B
( O
RC O
) O
users O
, O
were O
compared O
. O

An O
emotional O
facial O
expression O
( O
EFE O
) O
task O
consisting O
of O
a O
male O
and O
female O
face O
expressing O
six O
basic O
emotions O
( O
happiness O
, O
surprise O
, O
sadness O
, O
anger O
, O
fear O
, O
and O
disgust O
) O
was O
administered O
. O

Mean O
percent O
accuracy O
and O
latencies O
for O
correct O
responses O
across O
eight O
presentations O
of O
each O
basic O
emotion O
were O
derived O
. O

Participants O
were O
also O
assessed O
with O
the O
" O
Eyes O
task O
" O
to O
investigate O
their O
ability O
to O
recognize O
more O
complex O
emotional O
states O
and O
the O
Symptom O
CheckList O
- O
90 O
- O
Revised O
to O
measure O
psychopathology O
. O

RESULTS O
: O
There O
were O
no O
group O
differences O
in O
psychopathology O
or O
" O
eyes O
task O
" O
performance O
, O
but O
the O
RC O
group O
, O
who O
otherwise O
had O
similar O
illicit O
substance O
use O
histories O
to O
the O
OC B
group O
, O
exhibited O
impaired O
fear O
recognition O
accuracy O
compared O
to O
the O
OC B
and O
CN O
groups O
. O

The O
RC O
group O
also O
correctly O
identified O
anger O
, O
fear O
, O
happiness O
, O
and O
surprise O
, O
more O
slowly O
than O
CN O
, O
but O
not O
OC O
participants O
. O

The O
OC O
group O
was O
slower O
than O
CN O
when O
correctly O
identifying O
disgust O
. O

The O
selective O
deficit O
in O
fear O
recognition O
accuracy O
manifested O
by O
the O
RC O
group O
cannot O
be O
explained O
by O
the O
subacute O
effects O
of O
cocaine B
, O
or O
ecstasy B
, O
because O
recent O
and O
less O
recent O
users O
of O
these O
drugs O
within O
this O
group O
were O
similarly O
impaired O
. O

Possible O
parallels O
between O
RC B
users O
and O
psychopaths O
with O
respect O
to O
impaired O
fear O
recognition O
, O
amygdala O
dysfunction O
, O
and O
etiology O
are O
discussed O
. O

Damage O
of O
substantia O
nigra O
pars O
reticulata O
during O
pilocarpine B
- O
induced O
status O
epilepticus O
in O
the O
rat O
: O
immunohistochemical O
study O
of O
neurons O
, O
astrocytes O
and O
serum O
- O
protein O
extravasation O
. O

The O
substantia O
nigra O
has O
a O
gating O
function O
controlling O
the O
spread O
of O
epileptic O
seizure O
activity O
. O

Additionally O
, O
in O
models O
of O
prolonged O
status O
epilepticus O
the O
pars O
reticulata O
of O
substantia O
nigra O
( O
SNR O
) O
suffers O
from O
a O
massive O
lesion O
which O
may O
arise O
from O
a O
massive O
metabolic O
derangement O
and O
hyperexcitation O
developing O
in O
the O
activated O
SNR O
. O

In O
this O
study O
, O
status O
epilepticus O
was O
induced O
by O
systemic O
injection O
of O
pilocarpine B
in O
rats O
. O

The O
neuropathology O
of O
SNR O
was O
investigated O
using O
immunohistochemical O
techniques O
with O
the O
major O
emphasis O
on O
the O
time O
- O
course O
of O
changes O
in O
neurons O
and O
astrocytes O
. O

Animals O
surviving O
20 O
, O
30 O
, O
40 O
, O
60 O
min O
, O
2 O
, O
3 O
, O
6 O
hours O
, O
1 O
, O
2 O
, O
and O
3 O
days O
after O
induction O
of O
status O
epilepticus O
were O
perfusion O
- O
fixed O
, O
and O
brains O
processed O
for O
immunohistochemical O
staining O
of O
SNR O
. O

Nissl O
- O
staining O
and O
antibodies O
against O
the O
neuron O
- O
specific O
calcium B
- O
binding O
protein O
, O
parvalbumin O
, O
served O
to O
detect O
neuronal O
damage O
in O
SNR O
. O

Antibodies O
against O
the O
astroglia O
- O
specific O
cytoskeletal O
protein O
, O
glial O
fibrillary O
acidic O
protein O
( O
GFAP O
) O
, O
and O
against O
the O
glial O
calcium B
- O
binding O
protein O
, O
S O
- O
100 O
protein O
, O
were O
used O
to O
assess O
the O
status O
of O
astrocytes O
. O

Immunohistochemical O
staining O
for O
serum O
- O
albumin O
and O
immunoglobulins O
in O
brain O
tissue O
was O
taken O
as O
indicator O
of O
blood O
- O
brain O
barrier O
disturbances O
and O
vasogenic O
edema O
formation O
. O

Immunohistochemical O
staining O
indicated O
loss O
of O
GFAP O
- O
staining O
already O
at O
30 O
min O
after O
induction O
of O
seizures O
in O
an O
oval O
focus O
situated O
in O
the O
center O
of O
SNR O
while O
sparing O
medial O
and O
lateral O
aspects O
. O

At O
1 O
h O
there O
was O
additional O
vacuolation O
in O
S O
- O
100 O
protein O
staining O
. O

By O
2 O
hours O
, O
parvalbumin O
- O
staining O
changed O
in O
the O
central O
SNR O
indicating O
neuronal O
damage O
, O
and O
Nissl O
- O
staining O
visualized O
some O
neuronal O
distortion O
. O

Staining O
for O
serum O
- O
proteins O
occurred O
in O
a O
patchy O
manner O
throughout O
the O
forebrain O
during O
the O
first O
hours O
. O

By O
6 O
h O
, O
vasogenic O
edema O
covered O
the O
lesioned O
SNR O
. O

By O
24 O
h O
, O
glial O
and O
neuronal O
markers O
indicated O
a O
massive O
lesion O
in O
the O
center O
of O
SNR O
. O

By O
48 O
- O
72 O
h O
, O
astrocytes O
surrounding O
the O
lesion O
increased O
in O
size O
, O
and O
polymorphic O
phagocytotic O
cells O
invaded O
the O
damaged O
area O
. O

In O
a O
further O
group O
of O
animals O
surviving O
1 O
to O
5 O
days O
, O
conventional O
paraffin O
- O
sections O
confirmed O
the O
neuronal O
and O
glial O
damage O
of O
SNR O
. O

Additional O
pathology O
of O
similar O
quality O
was O
found O
in O
the O
globus O
pallidus O
. O

Since O
astrocytes O
were O
always O
damaged O
in O
parallel O
with O
neurons O
in O
SNR O
it O
is O
proposed O
that O
the O
anatomical O
and O
functional O
interrelationship O
between O
neurons O
and O
astrocytes O
is O
particularly O
tight O
in O
SNR O
. O

Both O
cell O
elements O
may O
suffer O
in O
common O
from O
metabolic O
disturbance O
and O
neurotransmitter O
dysfunction O
as O
occur O
during O
massive O
status O
epilepticus O
. O

Neuroprotective O
effects O
of O
melatonin B
upon O
the O
offspring O
cerebellar O
cortex O
in O
the O
rat O
model O
of O
BCNU B
- O
induced O
cortical O
dysplasia O
. O

Cortical O
dysplasia O
is O
a O
malformation O
characterized O
by O
defects O
in O
proliferation O
, O
migration O
and O
maturation O
. O

This O
study O
was O
designed O
to O
evaluate O
the O
alterations O
in O
offspring O
rat O
cerebellum O
induced O
by O
maternal O
exposure O
to O
carmustine B
- I
[ I
1 I
, I
3 I
- I
bis I
( I
2 I
- I
chloroethyl I
) I
- I
1 I
- I
nitrosoure I
] I
( O
BCNU B
) O
and O
to O
investigate O
the O
effects O
of O
exogenous O
melatonin B
upon O
cerebellar O
BCNU B
- O
induced O
cortical O
dysplasia O
, O
using O
histological O
and O
biochemical O
analyses O
. O

Pregnant O
Wistar O
rats O
were O
assigned O
to O
five O
groups O
: O
intact O
- O
control O
, O
saline O
- O
control O
, O
melatonin B
- O
treated O
, O
BCNU B
- O
exposed O
and O
BCNU B
- O
exposed O
plus O
melatonin B
. O

Rats O
were O
exposed O
to O
BCNU B
on O
embryonic O
day O
15 O
and O
melatonin B
was O
given O
until O
delivery O
. O

Immuno O
/ O
histochemistry O
and O
electron O
microscopy O
were O
carried O
out O
on O
the O
offspring O
cerebellum O
, O
and O
levels O
of O
malondialdehyde B
and O
superoxide B
dismutase O
were O
determined O
. O

Histopathologically O
, O
typical O
findings O
were O
observed O
in O
the O
cerebella O
from O
the O
control O
groups O
, O
but O
the O
findings O
consistent O
with O
early O
embryonic O
development O
were O
noted O
in O
BCNU B
- O
exposed O
cortical O
dysplasia O
group O
. O

There O
was O
a O
marked O
increase O
in O
the O
number O
of O
TUNEL O
positive O
cells O
and O
nestin O
positive O
cells O
in O
BCNU B
- O
exposed O
group O
, O
but O
a O
decreased O
immunoreactivity O
to O
glial O
fibrillary O
acidic O
protein O
, O
synaptophysin O
and O
transforming O
growth O
factor O
beta1 O
was O
observed O
, O
indicating O
a O
delayed O
maturation O
, O
and O
melatonin B
significantly O
reversed O
these O
changes O
. O

Malondialdehyde B
level O
in O
BCNU B
- O
exposed O
group O
was O
higher O
than O
those O
in O
control O
groups O
and O
melatonin B
decreased O
malondialdehyde B
levels O
in O
BCNU B
group O
( O
P O
< O
0 O
. O
01 O
) O
, O
while O
there O
were O
no O
significant O
differences O
in O
the O
superoxide B
dismutase O
levels O
between O
these O
groups O
. O

These O
data O
suggest O
that O
exposure O
of O
animals O
to O
BCNU B
during O
pregnancy O
leads O
to O
delayed O
maturation O
of O
offspring O
cerebellum O
and O
melatonin B
protects O
the O
cerebellum O
against O
the O
effects O
of O
BCNU B
. O

Reduced O
cardiotoxicity O
of O
doxorubicin B
given O
in O
the O
form O
of O
N B
- I
( I
2 I
- I
hydroxypropyl I
) I
methacrylamide I
conjugates O
: O
and O
experimental O
study O
in O
the O
rat O
. O

A O
rat O
model O
was O
used O
to O
evaluate O
the O
general O
acute O
toxicity O
and O
the O
late O
cardiotoxicity O
of O
4 O
mg O
/ O
kg O
doxorubicin B
( O
DOX B
) O
given O
either O
as O
free O
drug O
or O
in O
the O
form O
of O
three O
N B
- I
( I
2 I
- I
hydroxypropyl I
) I
methacrylamide I
( O
HPMA B
) O
copolymer O
conjugates O
. O

In O
these O
HPMA O
copolymers O
, O
DOX B
was O
covalently O
bound O
via O
peptide O
linkages O
that O
were O
either O
non O
- O
biodegradable O
( O
Gly O
- O
Gly O
) O
or O
degradable O
by O
lysosomal O
proteinases O
( O
Gly B
- I
Phe I
- I
Leu I
- I
Gly O
) O
. O

In O
addition O
, O
one O
biodegradable O
conjugate O
containing O
galactosamine B
was O
used O
; O
this O
residue O
was O
targeted O
to O
the O
liver O
. O

Over O
the O
first O
3 O
weeks O
after O
the O
i O
. O
v O
. O
administration O
of O
free O
and O
polymer O
- O
bound O
DOX B
, O
all O
animals O
showed O
a O
transient O
reduction O
in O
body O
weight O
. O

However O
, O
the O
maximal O
reduction O
in O
body O
weight O
seen O
in O
animals O
that O
received O
polymer O
- O
bound O
DOX B
( O
4 O
mg O
/ O
kg O
) O
was O
significantly O
lower O
than O
that O
observed O
in O
those O
that O
received O
free O
DOX B
( O
4 O
mg O
/ O
kg O
) O
or O
a O
mixture O
of O
the O
unmodified O
parent O
HPMA O
copolymer O
and O
free O
DOX B
( O
4 O
mg O
/ O
kg O
; O
P O
less O
than O
0 O
. O
01 O
) O
. O

Throughout O
the O
study O
( O
20 O
weeks O
) O
, O
deaths O
related O
to O
cardiotoxicity O
were O
observed O
only O
in O
animals O
that O
received O
either O
free O
DOX B
or O
the O
mixture O
of O
HPMA O
copolymer O
and O
free O
DOX B
; O
in O
these O
cases O
, O
histological O
investigations O
revealed O
marked O
changes O
in O
the O
heart O
that O
were O
consistent O
with O
DOX B
- O
induced O
cardiotoxicity O
. O

Sequential O
measurements O
of O
cardiac O
output O
in O
surviving O
animals O
that O
received O
either O
free O
DOX B
or O
the O
mixture O
of O
HPMA O
copolymer O
and O
free O
DOX B
showed O
a O
reduction O
of O
approximately O
30 O
% O
in O
function O
beginning O
at O
the O
4th O
week O
after O
drug O
administration O
. O

The O
heart O
rate O
in O
these O
animals O
was O
approximately O
12 O
% O
lower O
than O
that O
measured O
in O
age O
- O
matched O
control O
rats O
( O
P O
less O
than O
0 O
. O
05 O
) O
. O

Animals O
that O
were O
given O
the O
HPMA B
copolymer O
conjugates O
containing O
DOX B
exhibited O
no O
significant O
change O
in O
cardiac O
output O
throughout O
the O
study O
( O
P O
less O
than O
0 O
. O
05 O
) O
. O

In O
addition O
, O
no O
significant O
histological O
change O
was O
observed O
in O
the O
heart O
of O
animals O
that O
received O
DOX B
in O
the O
form O
of O
HPMA O
copolymer O
conjugates O
and O
were O
killed O
at O
the O
end O
of O
the O
study O
. O

However O
, O
these O
animals O
had O
shown O
a O
significant O
increase O
in O
heart O
rate O
beginning O
at O
8 O
weeks O
after O
drug O
administration O
( O
P O
less O
than O
0 O
. O
01 O
) O
. O
( O
ABSTRACT O
TRUNCATED O
AT O
400 O
WORDS O
) O

Corneal O
ulcers O
associated O
with O
aerosolized O
crack B
cocaine I
use O
. O

PURPOSE O
: O
We O
report O
4 O
cases O
of O
corneal O
ulcers O
associated O
with O
drug O
abuse O
. O

The O
pathogenesis O
of O
these O
ulcers O
and O
management O
of O
these O
patients O
are O
also O
reviewed O
. O

METHODS O
: O
Review O
of O
all O
cases O
of O
corneal O
ulcers O
associated O
with O
drug O
abuse O
seen O
at O
our O
institution O
from O
July O
2006 O
to O
December O
2006 O
. O

RESULTS O
: O
Four O
patients O
with O
corneal O
ulcers O
associated O
with O
crack B
cocaine I
use O
were O
reviewed O
. O

All O
corneal O
ulcers O
were O
cultured O
, O
and O
the O
patients O
were O
admitted O
to O
the O
hospital O
for O
intensive O
topical O
antibiotic O
treatment O
. O

Each O
patient O
received O
comprehensive O
health O
care O
, O
including O
medical O
and O
substance O
abuse O
consultations O
. O

Streptococcal O
organisms O
were O
found O
in O
3 O
cases O
and O
Capnocytophaga O
and O
Brevibacterium O
casei O
in O
1 O
patient O
. O

The O
infections O
responded O
to O
antibiotic O
treatment O
. O

Two O
patients O
needed O
a O
lateral O
tarsorrhaphy O
for O
persistent O
epithelial O
defects O
. O

CONCLUSIONS O
: O
Aerosolized O
crack B
cocaine I
use O
can O
be O
associated O
with O
the O
development O
of O
corneal O
ulcers O
. O

Drug O
abuse O
provides O
additional O
challenges O
for O
management O
. O

Not O
only O
treatment O
of O
their O
infections O
but O
also O
the O
overall O
poor O
health O
of O
the O
patients O
and O
increased O
risk O
of O
noncompliance O
need O
to O
be O
addressed O
. O

Comprehensive O
care O
may O
provide O
the O
patient O
the O
opportunity O
to O
discontinue O
their O
substance O
abuse O
, O
improve O
their O
overall O
health O
, O
and O
prevent O
future O
corneal O
complications O
. O

Topical O
0 O
. O
025 O
% O
capsaicin B
in O
chronic O
post O
- O
herpetic O
neuralgia O
: O
efficacy O
, O
predictors O
of O
response O
and O
long O
- O
term O
course O
. O

In O
order O
to O
evaluate O
the O
efficacy O
, O
time O
- O
course O
of O
action O
and O
predictors O
of O
response O
to O
topical O
capsaicin B
, O
39 O
patients O
with O
chronic O
post O
- O
herpetic O
neuralgia O
( O
PHN O
) O
, O
median O
duration O
24 O
months O
, O
were O
treated O
with O
0 O
. O
025 O
% O
capsaicin B
cream O
for O
8 O
weeks O
. O

During O
therapy O
the O
patients O
rated O
their O
pain O
on O
a O
visual O
analogue O
scale O
( O
VAS O
) O
and O
a O
verbal O
outcome O
scale O
. O

A O
follow O
- O
up O
investigation O
was O
performed O
10 O
- O
12 O
months O
after O
study O
onset O
on O
the O
patients O
who O
had O
improved O
. O

Nineteen O
patients O
( O
48 O
. O
7 O
% O
) O
substantially O
improved O
after O
the O
8 O
- O
week O
trial O
; O
5 O
( O
12 O
. O
8 O
% O
) O
discontinued O
therapy O
due O
to O
side O
- O
effects O
such O
as O
intolerable O
capsaicin B
- O
induced O
burning O
sensations O
( O
4 O
) O
or O
mastitis O
( O
1 O
) O
; O
15 O
( O
38 O
. O
5 O
% O
) O
reported O
no O
benefit O
. O

The O
decrease O
in O
VAS O
ratings O
was O
significant O
after O
2 O
weeks O
of O
continuous O
application O
. O

Of O
the O
responders O
72 O
. O
2 O
% O
were O
still O
improved O
at O
the O
follow O
- O
up O
; O
only O
one O
- O
third O
of O
them O
had O
continued O
application O
irregularly O
. O

Treatment O
effect O
was O
not O
dependent O
on O
patient O
' O
s O
age O
, O
duration O
or O
localization O
of O
PHN O
( O
trigeminal O
involvement O
was O
excluded O
) O
, O
sensory O
disturbance O
or O
pain O
character O
. O

Treatment O
response O
was O
not O
correlated O
with O
the O
incidence O
, O
time O
- O
course O
or O
severity O
of O
capsaicin B
- O
induced O
burning O
. O

If O
confirmed O
in O
controlled O
trials O
, O
the O
long O
- O
term O
results O
of O
this O
open O
, O
non O
- O
randomized O
study O
might O
indicate O
that O
the O
analgesic O
effect O
of O
capsaicin B
in O
PHN O
is O
mediated O
by O
both O
interference O
with O
neuropeptide O
metabolism O
and O
morphological O
changes O
( O
perhaps O
degeneration O
) O
of O
nociceptive O
afferents O
. O

Myo B
- I
inositol I
- I
1 I
- I
phosphate I
( O
MIP B
) O
synthase O
inhibition O
: O
in O
- O
vivo O
study O
in O
rats O
. O

Lithium B
and O
valproate B
are O
the O
prototypic O
mood O
stabilizers O
and O
have O
diverse O
structures O
and O
targets O
. O

Both O
drugs O
influence O
inositol B
metabolism O
. O

Lithium B
inhibits O
IMPase O
and O
valproate B
inhibits O
MIP O
synthase O
. O

This O
study O
shows O
that O
MIP O
synthase O
inhibition O
does O
not O
replicate O
or O
augment O
the O
effects O
of O
lithium B
in O
the O
inositol B
sensitive O
pilocarpine B
- O
induced O
seizures O
model O
. O

This O
lack O
of O
effects O
may O
stem O
from O
the O
low O
contribution O
of O
de O
- O
novo O
synthesis O
to O
cellular O
inositol B
supply O
or O
to O
the O
inhibition O
of O
the O
de O
- O
novo O
synthesis O
by O
lithium B
itself O
. O

Non O
- O
steroidal O
anti O
- O
inflammatory O
drugs O
- O
associated O
acute O
interstitial O
nephritis O
with O
granular O
tubular O
basement O
membrane O
deposits O
. O

Acute O
tubulo O
- O
interstitial O
nephritis O
( O
ATIN O
) O
is O
an O
important O
cause O
of O
acute O
renal O
failure O
resulting O
from O
a O
variety O
of O
insults O
, O
including O
immune O
complex O
- O
mediated O
tubulo O
- O
interstitial O
injury O
, O
but O
drugs O
such O
as O
non B
- I
steroidal I
anti I
- I
inflammatory I
drugs I
( O
NSAIDs O
) O
are O
a O
far O
more O
frequent O
cause O
. O

Overall O
, O
as O
an O
entity O
, O
ATIN O
remains O
under O
- O
diagnosed O
, O
as O
symptoms O
resolve O
spontaneously O
if O
the O
medication O
is O
stopped O
. O

We O
report O
on O
a O
14 O
- O
year O
- O
old O
boy O
who O
developed O
acute O
renal O
failure O
2 O
weeks O
after O
aortic O
valve O
surgery O
. O

He O
was O
put O
on O
aspirin B
following O
surgery O
and O
took O
ibuprofen B
for O
fever O
for O
nearly O
a O
week O
prior O
to O
presentation O
. O

He O
then O
presented O
to O
the O
emergency O
department O
feeling O
quite O
ill O
and O
was O
found O
to O
have O
a O
blood B
urea I
nitrogen I
( O
BUN B
) O
concentration O
of O
of O
147 O
mg O
/ O
dl O
, O
creatinine B
of O
15 O
. O
3 O
mg O
/ O
dl O
and O
serum O
potassium B
of O
8 O
. O
7 O
mEq O
/ O
l O
. O

Dialysis O
was O
immediately O
initiated O
. O

A O
kidney O
biopsy O
showed O
inflammatory O
infiltrate O
consistent O
with O
ATIN O
. O

However O
, O
in O
the O
tubular O
basement O
membrane O
( O
TBM O
) O
, O
very O
intense O
granular O
deposits O
of O
polyclonal O
IgG O
and O
C3 O
were O
noted O
. O

He O
needed O
dialysis O
for O
2 O
weeks O
and O
was O
treated O
successfully O
with O
steroids B
for O
6 O
months O
. O

His O
renal O
recovery O
and O
disappearance O
of O
proteinuria O
took O
a O
year O
. O

In O
conclusion O
, O
this O
is O
a O
first O
report O
of O
NSAIDs O
- O
associated O
ATIN O
, O
showing O
deposits O
of O
granular O
immune O
complex O
present O
only O
in O
the O
TBM O
and O
not O
in O
the O
glomeruli O
. O

Rifampicin B
- O
associated O
segmental O
necrotizing O
glomerulonephritis O
in O
staphylococcal O
endocarditis O
. O

Segmental O
necrotising O
glomerulonephritis O
has O
been O
reported O
as O
complication O
of O
rifampicin B
therapy O
in O
patients O
receiving O
treatment O
for O
tuberculosis O
. O

Changing O
epidemiology O
of O
infections O
such O
as O
infective O
endocarditis O
( O
IE O
) O
has O
led O
to O
an O
increase O
in O
the O
use O
of O
rifampicin B
for O
Staphylococcal O
infections O
. O

We O
describe O
a O
case O
of O
a O
patient O
with O
Staphylococcal O
IE O
who O
developed O
acute O
renal O
failure O
secondary O
to O
a O
segmental O
necrotising O
glomerulonephritis O
while O
being O
treated O
with O
rifampicin B
, O
and O
review O
the O
literature O
regarding O
this O
complication O
of O
rifampicin B
therapy O
. O

Rate O
of O
YMDD O
motif O
mutants O
in O
lamivudine B
- O
untreated O
Iranian O
patients O
with O
chronic O
hepatitis O
B O
virus O
infection O
. O

BACKGROUND O
: O
Lamivudine B
is O
used O
for O
the O
treatment O
of O
chronic O
hepatitis O
B O
patients O
. O

Recent O
studies O
show O
that O
the O
YMDD O
motif O
mutants O
( O
resistant O
hepatitis O
B O
virus O
) O
occur O
as O
natural O
genome O
variability O
in O
lamivudine B
- O
untreated O
chronic O
hepatitis O
B O
patients O
. O

In O
this O
study O
we O
aimed O
to O
determine O
the O
rate O
of O
YMDD O
motif O
mutants O
in O
lamivudine B
- O
untreated O
chronic O
hepatitis O
B O
patients O
in O
Iran O
. O

PATIENTS O
AND O
METHODS O
: O
A O
total O
of O
77 O
chronic O
hepatitis O
B O
patients O
who O
had O
not O
been O
treated O
with O
lamivudine B
were O
included O
in O
the O
study O
. O

Serum O
samples O
from O
patients O
were O
tested O
by O
polymerase O
chain O
reaction O
- O
restriction O
fragment O
length O
polymorphism O
( O
PCR O
- O
RFLP O
) O
for O
detection O
of O
YMDD O
motif O
mutants O
. O

All O
patients O
were O
also O
tested O
for O
liver O
enzymes O
, O
anti O
- O
HCV O
, O
HBeAg B
, O
and O
anti O
- O
HBe O
. O

RESULTS O
: O
Of O
the O
77 O
patients O
enrolled O
in O
the O
study O
, O
73 O
% O
were O
male O
and O
27 O
% O
were O
female O
. O

Mean O
ALT O
and O
AST O
levels O
were O
124 O
. O
4 O
+ O
/ O
- O
73 O
. O
4 O
and O
103 O
. O
1 O
+ O
/ O
- O
81 O
IU O
/ O
l O
, O
respectively O
. O

HBeAg B
was O
positive O
in O
40 O
% O
and O
anti O
- O
HBe O
in O
60 O
% O
of O
the O
patients O
. O

Anti O
- O
HCV O
was O
negative O
in O
all O
of O
them O
. O

YMDD O
motif O
mutants O
were O
not O
detected O
in O
any O
of O
the O
patients O
despite O
the O
liver O
enzyme O
levels O
and O
the O
presence O
of O
HBeAg B
or O
anti O
- O
HBe O
. O

CONCLUSION O
: O
Although O
the O
natural O
occurrence O
of O
YMDD O
motif O
mutants O
in O
lamivudine B
- O
untreated O
patients O
with O
chronic O
hepatitis O
B O
has O
been O
reported O
, O
these O
mutants O
were O
not O
detected O
in O
Iranian O
lamivudine B
- O
untreated O
chronic O
hepatitis O
B O
patients O
. O

Branch O
retinal O
vein O
occlusion O
and O
fluoxetine B
. O

A O
case O
of O
branch O
retinal O
vein O
occlusion O
associated O
with O
fluoxetine B
- O
induced O
secondary O
hypertension O
is O
described O
. O

Although O
an O
infrequent O
complication O
of O
selective O
serotonin B
reuptake O
inhibitor O
therapy O
, O
it O
is O
important O
that O
ophthalmologists O
are O
aware O
that O
these O
agents O
can O
cause O
hypertension O
because O
this O
class O
of O
drugs O
is O
widely O
prescribed O
. O

The O
differential O
effects O
of O
bupivacaine B
and O
lidocaine B
on O
prostaglandin B
E2 I
release O
, O
cyclooxygenase O
gene O
expression O
and O
pain O
in O
a O
clinical O
pain O
model O
. O

BACKGROUND O
: O
In O
addition O
to O
blocking O
nociceptive O
input O
from O
surgical O
sites O
, O
long O
- O
acting O
local O
anesthetics O
might O
directly O
modulate O
inflammation O
. O

In O
the O
present O
study O
, O
we O
describe O
the O
proinflammatory O
effects O
of O
bupivacaine B
on O
local O
prostaglandin B
E2 I
( O
PGE2 B
) O
production O
and O
cyclooxygenase O
( O
COX O
) O
gene O
expression O
that O
increases O
postoperative O
pain O
in O
human O
subjects O
. O

METHODS O
: O
Subjects O
( O
n O
= O
114 O
) O
undergoing O
extraction O
of O
impacted O
third O
molars O
received O
either O
2 O
% O
lidocaine B
or O
0 O
. O
5 O
% O
bupivacaine B
before O
surgery O
and O
either O
rofecoxib B
50 O
mg O
or O
placebo O
orally O
90 O
min O
before O
surgery O
and O
for O
the O
following O
48 O
h O
. O

Oral O
mucosal O
biopsies O
were O
taken O
before O
surgery O
and O
48 O
h O
after O
surgery O
. O

After O
extraction O
, O
a O
microdialysis O
probe O
was O
placed O
at O
the O
surgical O
site O
for O
PGE2 B
and O
thromboxane B
B2 I
( O
TXB2 B
) O
measurements O
. O

RESULTS O
: O
The O
bupivacaine B
/ O
rofecoxib B
group O
reported O
significantly O
less O
pain O
, O
as O
assessed O
by O
a O
visual O
analog O
scale O
, O
compared O
with O
the O
other O
three O
treatment O
groups O
over O
the O
first O
4 O
h O
. O

However O
, O
the O
bupivacaine B
/ O
placebo O
group O
reported O
significantly O
more O
pain O
at O
24 O
h O
and O
PGE2 B
levels O
during O
the O
first O
4 O
h O
were O
significantly O
higher O
than O
the O
other O
three O
treatment O
groups O
. O

Moreover O
, O
bupivacaine B
significantly O
increased O
COX O
- O
2 O
gene O
expression O
at O
48 O
h O
as O
compared O
with O
the O
lidocaine B
/ O
placebo O
group O
. O

Thromboxane B
levels O
were O
not O
significantly O
affected O
by O
any O
of O
the O
treatments O
, O
indicating O
that O
the O
effects O
seen O
were O
attributable O
to O
inhibition O
of O
COX O
- O
2 O
, O
but O
not O
COX O
- O
1 O
. O

CONCLUSIONS O
: O
These O
results O
suggest O
that O
bupivacaine B
stimulates O
COX O
- O
2 O
gene O
expression O
after O
tissue O
injury O
, O
which O
is O
associated O
with O
higher O
PGE2 B
production O
and O
pain O
after O
the O
local O
anesthetic O
effect O
dissipates O
. O

p75NTR O
expression O
in O
rat O
urinary O
bladder O
sensory O
neurons O
and O
spinal O
cord O
with O
cyclophosphamide B
- O
induced O
cystitis O
. O

A O
role O
for O
nerve O
growth O
factor O
( O
NGF O
) O
in O
contributing O
to O
increased O
voiding O
frequency O
and O
altered O
sensation O
from O
the O
urinary O
bladder O
has O
been O
suggested O
. O

Previous O
studies O
have O
examined O
the O
expression O
and O
regulation O
of O
tyrosine B
kinase O
receptors O
( O
Trks O
) O
in O
micturition O
reflexes O
with O
urinary O
bladder O
inflammation O
. O

The O
present O
studies O
examine O
the O
expression O
and O
regulation O
of O
another O
receptor O
known O
to O
bind O
NGF O
, O
p75 O
( O
NTR O
) O
, O
after O
various O
durations O
of O
bladder O
inflammation O
induced O
by O
cyclophosphamide B
( O
CYP B
) O
. O

CYP B
- O
induced O
cystitis O
increased O
( O
P O
< O
or O
= O
0 O
. O
001 O
) O
p75 O
( O
NTR O
) O
expression O
in O
the O
superficial O
lateral O
and O
medial O
dorsal O
horn O
in O
L1 O
- O
L2 O
and O
L6 O
- O
S1 O
spinal O
segments O
. O

The O
number O
of O
p75 O
( O
NTR O
) O
- O
immunoreactive O
( O
- O
IR O
) O
cells O
in O
the O
lumbosacral O
dorsal O
root O
ganglia O
( O
DRG O
) O
also O
increased O
( O
P O
< O
or O
= O
0 O
. O
05 O
) O
with O
CYP B
- O
induced O
cystitis O
( O
acute O
, O
intermediate O
, O
and O
chronic O
) O
. O

Quantitative O
, O
real O
- O
time O
polymerase O
chain O
reaction O
also O
demonstrated O
significant O
increases O
( O
P O
< O
or O
= O
0 O
. O
01 O
) O
in O
p75 O
( O
NTR O
) O
mRNA O
in O
DRG O
with O
intermediate O
and O
chronic O
CYP B
- O
induced O
cystitis O
. O

Retrograde O
dye O
- O
tracing O
techniques O
with O
Fastblue O
were O
used O
to O
identify O
presumptive O
bladder O
afferent O
cells O
in O
the O
lumbosacral O
DRG O
. O

In O
bladder O
afferent O
cells O
in O
DRG O
, O
p75 O
( O
NTR O
) O
- O
IR O
was O
also O
increased O
( O
P O
< O
or O
= O
0 O
. O
01 O
) O
with O
cystitis O
. O

In O
addition O
to O
increases O
in O
p75 O
( O
NTR O
) O
- O
IR O
in O
DRG O
cell O
bodies O
, O
increases O
( O
P O
< O
or O
= O
0 O
. O
001 O
) O
in O
pericellular O
( O
encircling O
DRG O
cells O
) O
p75 O
( O
NTR O
) O
- O
IR O
in O
DRG O
also O
increased O
. O

Confocal O
analyses O
demonstrated O
that O
pericellular O
p75 O
( O
NTR O
) O
- O
IR O
was O
not O
colocalized O
with O
the O
glial O
marker O
, O
glial O
fibrillary O
acidic O
protein O
( O
GFAP O
) O
. O

These O
studies O
demonstrate O
that O
p75 O
( O
NTR O
) O
expression O
in O
micturition O
reflexes O
is O
present O
constitutively O
and O
modified O
by O
bladder O
inflammation O
. O

The O
functional O
significance O
of O
p75 O
( O
NTR O
) O
expression O
in O
micturition O
reflexes O
remains O
to O
be O
determined O
. O

Azathioprine B
- O
induced O
suicidal O
erythrocyte O
death O
. O

BACKGROUND O
: O
Azathioprine B
is O
widely O
used O
as O
an O
immunosuppressive O
drug O
. O

The O
side O
effects O
of O
azathioprine B
include O
anemia O
, O
which O
has O
been O
attributed O
to O
bone O
marrow O
suppression O
. O

Alternatively O
, O
anemia O
could O
result O
from O
accelerated O
suicidal O
erythrocyte O
death O
or O
eryptosis O
, O
which O
is O
characterized O
by O
exposure O
of O
phosphatidylserine B
( O
PS O
) O
at O
the O
erythrocyte O
surface O
and O
by O
cell O
shrinkage O
. O

METHODS O
: O
The O
present O
experiments O
explored O
whether O
azathioprine B
influences O
eryptosis O
. O

According O
to O
annexin O
V O
binding O
, O
erythrocytes O
from O
patients O
indeed O
showed O
a O
significant O
increase O
of O
PS O
exposure O
within O
1 O
week O
of O
treatment O
with O
azathioprine B
. O

In O
a O
second O
series O
, O
cytosolic O
Ca2 B
+ O
activity O
( O
Fluo3 B
fluorescence O
) O
, O
cell O
volume O
( O
forward O
scatter O
) O
, O
and O
PS O
- O
exposure O
( O
annexin O
V O
binding O
) O
were O
determined O
by O
FACS O
analysis O
in O
erythrocytes O
from O
healthy O
volunteers O
. O

RESULTS O
: O
Exposure O
to O
azathioprine B
( O
> O
or O
= O
2 O
microg O
/ O
mL O
) O
for O
48 O
hours O
increased O
cytosolic O
Ca2 B
+ O
activity O
and O
annexin O
V O
binding O
and O
decreased O
forward O
scatter O
. O

The O
effect O
of O
azathioprine B
on O
both O
annexin O
V O
binding O
and O
forward O
scatter O
was O
significantly O
blunted O
in O
the O
nominal O
absence O
of O
extracellular O
Ca2 B
+ O
. O

CONCLUSIONS O
: O
Azathioprine B
triggers O
suicidal O
erythrocyte O
death O
, O
an O
effect O
presumably O
contributing O
to O
azathioprine B
- O
induced O
anemia O
. O

Levetiracetam B
as O
an O
adjunct O
to O
phenobarbital B
treatment O
in O
cats O
with O
suspected O
idiopathic O
epilepsy O
. O

OBJECTIVE O
: O
To O
assess O
pharmacokinetics O
, O
efficacy O
, O
and O
tolerability O
of O
oral O
levetiracetam B
administered O
as O
an O
adjunct O
to O
phenobarbital B
treatment O
in O
cats O
with O
poorly O
controlled O
suspected O
idiopathic O
epilepsy O
. O

DESIGN O
- O
Open O
- O
label O
, O
noncomparative O
clinical O
trial O
. O

ANIMALS O
: O
12 O
cats O
suspected O
to O
have O
idiopathic O
epilepsy O
that O
was O
poorly O
controlled O
with O
phenobarbital B
or O
that O
had O
unacceptable O
adverse O
effects O
when O
treated O
with O
phenobarbital B
. O

PROCEDURES O
: O
Cats O
were O
treated O
with O
levetiracetam B
( O
20 O
mg O
/ O
kg O
[ O
9 O
. O
1 O
mg O
/ O
lb O
] O
, O
PO O
, O
q O
8 O
h O
) O
. O

After O
a O
minimum O
of O
1 O
week O
of O
treatment O
, O
serum O
levetiracetam B
concentrations O
were O
measured O
before O
and O
2 O
, O
4 O
, O
and O
6 O
hours O
after O
drug O
administration O
, O
and O
maximum O
and O
minimum O
serum O
concentrations O
and O
elimination O
half O
- O
life O
were O
calculated O
. O

Seizure O
frequencies O
before O
and O
after O
initiation O
of O
levetiracetam B
treatment O
were O
compared O
, O
and O
adverse O
effects O
were O
recorded O
. O

RESULTS O
: O
Median O
maximum O
serum O
levetiracetam B
concentration O
was O
25 O
. O
5 O
microg O
/ O
mL O
, O
median O
minimum O
serum O
levetiracetam B
concentration O
was O
8 O
. O
3 O
microg O
/ O
mL O
, O
and O
median O
elimination O
half O
- O
life O
was O
2 O
. O
9 O
hours O
. O

Median O
seizure O
frequency O
prior O
to O
treatment O
with O
levetiracetam B
( O
2 O
. O
1 O
seizures O
/ O
mo O
) O
was O
significantly O
higher O
than O
median O
seizure O
frequency O
after O
initiation O
of O
levetiracetam B
treatment O
( O
0 O
. O
42 O
seizures O
/ O
mo O
) O
, O
and O
7 O
of O
10 O
cats O
were O
classified O
as O
having O
responded O
to O
levetiracetam B
treatment O
( O
ie O
, O
reduction O
in O
seizure O
frequency O
of O
> O
or O
= O
50 O
% O
) O
. O

Two O
cats O
had O
transient O
lethargy O
and O
inappetence O
. O

CONCLUSIONS O
AND O
CLINICAL O
RELEVANCE O
: O
Results O
suggested O
that O
levetiracetam B
is O
well O
tolerated O
in O
cats O
and O
may O
be O
useful O
as O
an O
adjunct O
to O
phenobarbital B
treatment O
in O
cats O
with O
idiopathic O
epilepsy O
. O

Serotonin B
reuptake O
inhibitors O
, O
paranoia O
, O
and O
the O
ventral O
basal O
ganglia O
. O

Antidepressants B
have O
previously O
been O
associated O
with O
paranoid O
reactions O
in O
psychiatric O
patients O
. O

Five O
cases O
of O
paranoid O
exacerbation O
with O
the O
serotonin B
reuptake O
inhibitors O
fluoxetine B
and O
amitriptyline B
are O
reported O
here O
. O

Elements O
common O
to O
these O
cases O
included O
a O
history O
of O
paranoid O
symptomatology O
and O
the O
concomitant O
occurrence O
of O
depressive O
and O
psychotic O
symptoms O
. O

Complicated O
depressive O
disorders O
( O
including O
atypicality O
of O
course O
and O
symptomatology O
, O
chronicity O
, O
psychosis O
, O
bipolarity O
, O
and O
secondary O
onset O
in O
the O
course O
of O
a O
primary O
psychosis O
) O
may O
present O
particular O
vulnerability O
to O
paranoid O
exacerbations O
associated O
with O
serotonin B
reuptake O
inhibitors O
. O

Although O
the O
pharmacology O
and O
neurobiology O
of O
paranoia O
remain O
cryptic O
, O
several O
mechanisms O
, O
including O
5HT3 O
receptor O
- O
mediated O
dopamine B
release O
, O
beta O
- O
noradrenergic O
receptor O
downregulation O
, O
or O
GABAB B
receptor O
upregulation O
acting O
in O
the O
vicinity O
of O
the O
ventral O
basal O
ganglia O
( O
possibly O
in O
lateral O
orbitofrontal O
or O
anterior O
cingulate O
circuits O
) O
, O
might O
apply O
to O
this O
phenomenon O
. O

These O
cases O
call O
attention O
to O
possible O
paranoid O
exacerbations O
with O
serotonin B
reuptake O
blockers O
in O
select O
patients O
and O
raise O
neurobiological O
considerations O
regarding O
paranoia O
. O

Clinical O
comparison O
of O
cardiorespiratory O
effects O
during O
unilateral O
and O
conventional O
spinal O
anaesthesia O
. O

BACKGROUND O
: O
Spinal O
anaesthesia O
is O
widely O
employed O
in O
clinical O
practice O
but O
has O
the O
main O
drawback O
of O
post O
- O
spinal O
block O
hypotension O
. O

Efforts O
must O
therefore O
continue O
to O
be O
made O
to O
obviate O
this O
setback O
OBJECTIVE O
: O
To O
evaluate O
the O
cardiovascular O
and O
respiratory O
changes O
during O
unilateral O
and O
conventional O
spinal O
anaesthesia O
. O

METHODS O
: O
With O
ethical O
approval O
, O
we O
studied O
74 O
American O
Society O
of O
Anesthesiologists O
( O
ASA O
) O
, O
physical O
status O
class O
1 O
and O
2 O
patients O
scheduled O
for O
elective O
unilateral O
lower O
limb O
surgery O
. O

Patients O
were O
randomly O
allocated O
into O
one O
of O
two O
groups O
: O
lateral O
and O
conventional O
spinal O
anaesthesia O
groups O
. O

In O
the O
lateral O
position O
with O
operative O
side O
down O
, O
patients O
recived O
10 O
mg O
( O
2mls O
) O
of O
0 O
. O
5 O
% O
hyperbaric O
bupivacaine B
through O
a O
25 O
- O
gauge O
spinal O
needle O
. O

Patients O
in O
the O
unilateral O
group O
were O
maintained O
in O
the O
lateral O
position O
for O
15 O
minutes O
following O
spinal O
injection O
while O
those O
in O
the O
conventional O
group O
were O
turned O
supine O
immediately O
after O
injection O
. O

Blood O
pressure O
, O
heart O
rate O
, O
respiratory O
rate O
and O
oxygen B
saturation O
were O
monitored O
over O
1 O
hour O
. O

RESULTS O
: O
Three O
patients O
( O
8 O
. O
1 O
% O
) O
in O
the O
unilateral O
group O
and O
5 O
( O
13 O
. O
5 O
% O
) O
in O
the O
conventional O
group O
developed O
hypotension O
, O
P O
= O
0 O
. O
71 O
. O

Four O
( O
10 O
. O
8 O
% O
) O
patients O
in O
the O
conventional O
group O
and O
1 O
( O
2 O
. O
7 O
% O
) O
in O
the O
unilateral O
group O
, O
P O
= O
0 O
. O
17 O
required O
epinephrine B
infusion O
to O
treat O
hypotension O
. O

Patients O
in O
the O
conventional O
group O
had O
statistically O
significant O
greater O
fall O
in O
the O
systolic O
blood O
pressures O
at O
15 O
, O
30 O
and O
45 O
minutes O
when O
compared O
to O
the O
baseline O
( O
P O
= O
0 O
. O
003 O
, O
0 O
. O
001 O
and O
0 O
. O
004 O
) O
. O

The O
mean O
respiratory O
rate O
and O
oxygen B
saturations O
in O
the O
two O
groups O
were O
similar O
. O

CONCLUSION O
: O
Compared O
to O
conventional O
spinal O
anaesthesia O
, O
unilateral O
spinal O
anaesthesia O
was O
associated O
with O
fewer O
cardiovascular O
perturbations O
. O

Also O
, O
the O
type O
of O
spinal O
block O
instituted O
affected O
neither O
the O
respiratory O
rate O
nor O
the O
arterial O
oxygen B
saturation O
. O

Spectrum O
of O
adverse O
events O
after O
generic O
HAART O
in O
southern O
Indian O
HIV O
- O
infected O
patients O
. O

To O
determine O
the O
incidence O
of O
clinically O
significant O
adverse O
events O
after O
long O
- O
term O
, O
fixed O
- O
dose O
, O
generic O
highly O
active O
antiretroviral O
therapy O
( O
HAART O
) O
use O
among O
HIV O
- O
infected O
individuals O
in O
South O
India O
, O
we O
examined O
the O
experiences O
of O
3154 O
HIV O
- O
infected O
individuals O
who O
received O
a O
minimum O
of O
3 O
months O
of O
generic O
HAART O
between O
February O
1996 O
and O
December O
2006 O
at O
a O
tertiary O
HIV O
care O
referral O
center O
in O
South O
India O
. O

The O
most O
common O
regimens O
were O
3TC B
+ O
d4T B
+ O
nevirapine B
( O
NVP B
) O
( O
54 O
. O
8 O
% O
) O
, O
zidovudine B
( O
AZT B
) O
+ O
3TC B
+ O
NVP B
( O
14 O
. O
5 O
% O
) O
, O
3TC B
+ O
d4T B
+ O
efavirenz B
( O
EFV B
) O
( O
20 O
. O
1 O
% O
) O
, O
and O
AZT B
+ O
3TC B
+ O
EFV B
( O
5 O
. O
4 O
% O
) O
. O

The O
most O
common O
adverse O
events O
and O
median O
CD4 O
at O
time O
of O
event O
were O
rash O
( O
15 O
. O
2 O
% O
; O
CD4 O
, O
285 O
cells O
/ O
microL O
) O
and O
peripheral O
neuropathy O
( O
9 O
. O
0 O
% O
and O
348 O
cells O
/ O
microL O
) O
. O

Clinically O
significant O
anemia O
( O
hemoglobin O
< O
7 O
g O
/ O
dL O
) O
was O
observed O
in O
5 O
. O
4 O
% O
of O
patients O
( O
CD4 O
, O
165 O
cells O
/ O
microL O
) O
and O
hepatitis O
( O
clinical O
jaundice O
with O
alanine B
aminotransferase O
> O
5 O
times O
upper O
limits O
of O
normal O
) O
in O
3 O
. O
5 O
% O
of O
patients O
( O
CD4 O
, O
260 O
cells O
/ O
microL O
) O
. O

Women O
were O
significantly O
more O
likely O
to O
experience O
lactic O
acidosis O
, O
while O
men O
were O
significantly O
more O
likely O
to O
experience O
immune O
reconstitution O
syndrome O
( O
p O
< O
0 O
. O
05 O
) O
. O

Among O
the O
patients O
with O
1 O
year O
of O
follow O
- O
up O
, O
NVP B
therapy O
was O
significantly O
associated O
with O
developing O
rash O
and O
d4T B
therapy O
with O
developing O
peripheral O
neuropathy O
( O
p O
< O
0 O
. O
05 O
) O
. O

Anemia O
and O
hepatitis O
often O
occur O
within O
12 O
weeks O
of O
initiating O
generic O
HAART O
. O

Frequent O
and O
early O
monitoring O
for O
these O
toxicities O
is O
warranted O
in O
developing O
countries O
where O
generic O
HAART O
is O
increasingly O
available O
. O

Thalidomide B
and O
sensory O
neurotoxicity O
: O
a O
neurophysiological O
study O
. O

BACKGROUND O
: O
Recent O
studies O
confirmed O
a O
high O
incidence O
of O
sensory O
axonal O
neuropathy O
in O
patients O
treated O
with O
different O
doses O
of O
thalidomide B
. O

The O
study O
' O
s O
aims O
were O
to O
measure O
variations O
in O
sural O
nerve O
sensory O
action O
potential O
( O
SAP O
) O
amplitude O
in O
patients O
with O
refractory O
cutaneous O
lupus O
erythematosus O
( O
CLE O
) O
treated O
with O
thalidomide B
and O
use O
these O
findings O
to O
identify O
the O
neurotoxic O
potential O
of O
thalidomide B
and O
the O
recovery O
capacity O
of O
sensory O
fibres O
after O
discontinuation O
of O
treatment O
. O

PATIENTS O
AND O
METHODS O
: O
Clinical O
and O
electrophysiological O
data O
in O
12 O
female O
patients O
with O
CLE O
during O
treatment O
with O
thalidomide B
and O
up O
to O
47 O
months O
after O
discontinuation O
of O
treatment O
were O
analysed O
. O

Sural O
nerve O
SAP O
amplitude O
reduction O
> O
or O
= O
40 O
% O
was O
the O
criteria O
for O
discontinuing O
therapy O
. O

RESULTS O
: O
During O
treatment O
, O
11 O
patients O
showed O
a O
reduction O
in O
sural O
nerve O
SAP O
amplitude O
compared O
to O
baseline O
values O
( O
9 O
with O
a O
reduction O
> O
or O
= O
50 O
% O
and O
2 O
< O
50 O
% O
) O
. O

One O
patient O
showed O
no O
changes O
in O
SAP O
amplitude O
. O

Five O
patients O
complained O
of O
paresthesias O
and O
leg O
cramps O
. O

After O
thalidomide B
treatment O
, O
sural O
SAP O
amplitude O
recovered O
in O
3 O
patients O
. O

At O
detection O
of O
reduction O
in O
sural O
nerve O
SAP O
amplitude O
, O
the O
median O
thalidomide B
cumulative O
dose O
was O
21 O
. O
4 O
g O
. O

The O
threshold O
neurotoxic O
dosage O
is O
lower O
than O
previously O
reported O
. O

CONCLUSIONS O
: O
Sural O
nerve O
SAP O
amplitude O
reduction O
is O
a O
reliable O
and O
sensitive O
marker O
of O
degeneration O
and O
recovery O
of O
sensory O
fibres O
. O

This O
electrophysiological O
parameter O
provides O
information O
about O
subclinical O
neurotoxic O
potential O
of O
thalidomide B
but O
is O
not O
helpful O
in O
predicting O
the O
appearance O
of O
sensory O
symptoms O
. O

Five O
cases O
of O
encephalitis O
during O
treatment O
of O
loiasis O
with O
diethylcarbamazine B
. O

Five O
cases O
of O
encephalitis O
following O
treatment O
with O
diethylcarbamazine B
( O
DEC B
) O
were O
observed O
in O
Congolese O
patients O
with O
Loa O
loa O
filariasis O
. O

Two O
cases O
had O
a O
fatal O
outcome O
and O
one O
resulted O
in O
severe O
sequelae O
. O

The O
notable O
fact O
was O
that O
this O
complication O
occurred O
in O
three O
patients O
hospitalized O
before O
treatment O
began O
, O
with O
whom O
particularly O
strict O
therapeutic O
precautions O
were O
taken O
, O
i O
. O
e O
. O
, O
initial O
dose O
less O
than O
10 O
mg O
of O
DEC B
, O
very O
gradual O
dose O
increases O
, O
and O
associated O
anti O
- O
allergic O
treatment O
. O

This O
type O
of O
drug O
- O
induced O
complication O
may O
not O
be O
that O
uncommon O
in O
highly O
endemic O
regions O
. O

It O
occurs O
primarily O
, O
but O
not O
exclusively O
, O
in O
subjects O
presenting O
with O
a O
high O
microfilarial O
load O
. O

The O
relationship O
between O
the O
occurrence O
of O
encephalitis O
and O
the O
decrease O
in O
microfilaremia O
is O
evident O
. O

The O
pathophysiological O
mechanisms O
are O
discussed O
in O
the O
light O
of O
these O
observations O
and O
the O
few O
other O
comments O
on O
this O
subject O
published O
in O
the O
literature O
. O

Amiodarone B
- O
related O
pulmonary O
mass O
and O
unique O
membranous O
glomerulonephritis O
in O
a O
patient O
with O
valvular O
heart O
disease O
: O
Diagnostic O
pitfall O
and O
new O
findings O
. O

Amiodarone B
is O
an O
anti O
- O
arrhythmic O
drug O
for O
life O
- O
threatening O
tachycardia O
, O
but O
various O
adverse O
effects O
have O
been O
reported O
. O

Reported O
herein O
is O
an O
autopsy O
case O
of O
valvular O
heart O
disease O
, O
in O
a O
patient O
who O
developed O
a O
lung O
mass O
( O
1 O
. O
5 O
cm O
in O
diameter O
) O
and O
proteinuria O
( O
2 O
. O
76 O
g O
/ O
day O
) O
after O
treatment O
with O
amiodarone B
for O
a O
long O
time O
. O

The O
lung O
mass O
was O
highly O
suspected O
to O
be O
lung O
cancer O
on O
CT O
and O
positron O
emission O
tomography O
, O
but O
histologically O
the O
lesion O
was O
composed O
of O
lymphoplasmacytic O
infiltrates O
in O
alveolar O
walls O
and O
intra O
- O
alveolar O
accumulation O
of O
foamy O
macrophages O
containing O
characteristic O
myelinoid O
bodies O
, O
indicating O
that O
it O
was O
an O
amiodarone B
- O
related O
lesion O
. O

In O
addition O
, O
the O
lung O
tissue O
had O
unevenly O
distributed O
hemosiderin O
deposition O
, O
and O
abnormally O
tortuous O
capillaries O
were O
seen O
in O
the O
mass O
and O
in O
heavily O
hemosiderotic O
lung O
portions O
outside O
the O
mass O
. O

In O
the O
kidneys O
, O
glomeruli O
had O
membrane O
spikes O
, O
prominent O
swelling O
of O
podocytes O
and O
subepithelial O
deposits O
, O
which O
were O
sometimes O
large O
and O
hump O
- O
like O
. O

Autoimmune O
diseases O
, O
viral O
hepatitis O
, O
malignant O
neoplasms O
or O
other O
diseases O
with O
a O
known O
relationship O
to O
membranous O
glomerulonephritis O
were O
not O
found O
. O

The O
present O
case O
highlights O
the O
possibility O
that O
differential O
diagnosis O
between O
an O
amiodarone B
- O
related O
pulmonary O
lesion O
and O
a O
neoplasm O
can O
be O
very O
difficult O
radiologically O
, O
and O
suggests O
that O
membranous O
glomerulonephritis O
might O
be O
another O
possible O
complication O
of O
amiodarone B
treatment O
. O

Risk O
of O
coronary O
artery O
disease O
associated O
with O
initial O
sulphonylurea B
treatment O
of O
patients O
with O
type O
2 O
diabetes O
: O
a O
matched O
case O
- O
control O
study O
. O

AIMS O
: O
This O
study O
sought O
to O
assess O
the O
risk O
of O
developing O
coronary O
artery O
disease O
( O
CAD O
) O
associated O
with O
initial O
treatment O
of O
type O
2 O
diabetes O
with O
different O
sulphonylureas B
. O

METHODS O
: O
In O
type O
2 O
diabetic O
patients O
, O
cases O
who O
developed O
CAD O
were O
compared O
retrospectively O
with O
controls O
that O
did O
not O
. O

The O
20 O
- O
year O
risk O
of O
CAD O
at O
diagnosis O
of O
diabetes O
, O
using O
the O
UKPDS O
risk O
engine O
, O
was O
used O
to O
match O
cases O
with O
controls O
. O

RESULTS O
: O
The O
76 O
cases O
of O
CAD O
were O
compared O
with O
152 O
controls O
. O

The O
hazard O
of O
developing O
CAD O
( O
95 O
% O
CI O
) O
associated O
with O
initial O
treatment O
increased O
by O
2 O
. O
4 O
- O
fold O
( O
1 O
. O
3 O
- O
4 O
. O
3 O
, O
P O
= O
0 O
. O
004 O
) O
with O
glibenclamide B
; O
2 O
- O
fold O
( O
0 O
. O
9 O
- O
4 O
. O
6 O
, O
P O
= O
0 O
. O
099 O
) O
with O
glipizide B
; O
2 O
. O
9 O
- O
fold O
( O
1 O
. O
6 O
- O
5 O
. O
1 O
, O
P O
= O
0 O
. O
000 O
) O
with O
either O
, O
and O
was O
unchanged O
with O
metformin B
. O

The O
hazard O
decreased O
0 O
. O
3 O
- O
fold O
( O
0 O
. O
7 O
- O
1 O
. O
7 O
, O
P O
= O
0 O
. O
385 O
) O
with O
glimepiride B
, O
0 O
. O
4 O
- O
fold O
( O
0 O
. O
7 O
- O
1 O
. O
3 O
, O
P O
= O
0 O
. O
192 O
) O
with O
gliclazide B
, O
and O
0 O
. O
4 O
- O
fold O
( O
0 O
. O
7 O
- O
1 O
. O
1 O
, O
P O
= O
0 O
. O
09 O
) O
with O
either O
. O

CONCLUSIONS O
: O
Initiating O
treatment O
of O
type O
2 O
diabetes O
with O
glibenclamide B
or O
glipizide B
is O
associated O
with O
increased O
risk O
of O
CAD O
in O
comparison O
to O
gliclazide B
or O
glimepiride B
. O

If O
confirmed O
, O
this O
may O
be O
important O
because O
most O
Indian O
patients O
receive O
the O
cheaper O
older O
sulphonylureas B
, O
and O
present O
guidelines O
do O
not O
distinguish O
between O
individual O
agents O
. O

Reduced O
progression O
of O
adriamycin B
nephropathy O
in O
spontaneously O
hypertensive O
rats O
treated O
by O
losartan B
. O

BACKGROUND O
: O
The O
aim O
of O
the O
study O
was O
to O
investigate O
the O
antihypertensive O
effects O
of O
angiotensin B
II I
type O
- O
1 O
receptor O
blocker O
, O
losartan B
, O
and O
its O
potential O
in O
slowing O
down O
renal O
disease O
progression O
in O
spontaneously O
hypertensive O
rats O
( O
SHR O
) O
with O
adriamycin B
( O
ADR B
) O
nephropathy O
. O

METHODS O
: O
Six O
- O
month O
- O
old O
female O
SHR O
were O
randomly O
selected O
in O
six O
groups O
. O

Two O
control O
groups O
( O
SH O
( O
6 O
) O
, O
SH O
( O
12 O
) O
) O
received O
vehicle O
. O

Groups O
ADR B
( O
6 O
) O
, O
ADR B
+ O
LOS O
( O
6 O
) O
and O
ADR B
( O
12 O
) O
, O
and O
ADR B
+ O
LOS O
( O
12 O
) O
received O
ADR B
( O
2 O
mg O
/ O
kg O
/ O
b O
. O
w O
. O
i O
. O
v O
. O
) O
twice O
in O
a O
3 O
- O
week O
interval O
. O

Group O
ADR B
+ O
LOS B
( O
6 O
) O
received O
losartan B
( O
10 O
mg O
/ O
kg O
/ O
b O
. O
w O
. O
/ O
day O
by O
gavages O
) O
for O
6 O
weeks O
and O
group O
ADR B
+ O
LOS B
( O
12 O
) O
for O
12 O
weeks O
after O
second O
injection O
of O
ADR B
. O

Animals O
were O
killed O
after O
6 O
or O
12 O
weeks O
, O
respectively O
. O

Haemodynamic O
measurements O
were O
performed O
on O
anaesthetized O
animals O
, O
blood O
and O
urine O
samples O
were O
taken O
for O
biochemical O
analysis O
and O
the O
left O
kidney O
was O
processed O
for O
morphological O
studies O
. O

RESULTS O
: O
Short O
- O
term O
losartan B
treatment O
, O
besides O
antihypertensive O
effect O
, O
improved O
glomerular O
filtration O
rate O
and O
ameliorated O
glomerulosclerosis O
resulting O
in O
decreased O
proteinuria O
. O

Prolonged O
treatment O
with O
losartan B
showed O
further O
reduction O
of O
glomerulosclerosis O
associated O
with O
reduced O
progression O
of O
tubular O
atrophy O
and O
interstitial O
fibrosis O
, O
thus O
preventing O
heavy O
proteinuria O
and O
chronic O
renal O
failure O
. O

Losartan B
reduced O
uraemia O
and O
increased O
urea B
clearance O
in O
advanced O
ADR B
nephropathy O
in O
SHR O
. O

Histological O
examination O
showed O
that O
losartan B
could O
prevent O
tubular O
atrophy O
, O
interstitial O
infiltration O
and O
fibrosis O
in O
ADR B
nephropathy O
. O

CONCLUSION O
: O
Losartan B
reduces O
the O
rate O
of O
progression O
of O
ADR B
- O
induced O
focal O
segmental O
glomerulosclerosis O
to O
end O
- O
stage O
renal O
disease O
in O
SHR O
. O

The O
risks O
of O
aprotinin O
and O
tranexamic B
acid I
in O
cardiac O
surgery O
: O
a O
one O
- O
year O
follow O
- O
up O
of O
1188 O
consecutive O
patients O
. O

BACKGROUND O
: O
Our O
aim O
was O
to O
investigate O
postoperative O
complications O
and O
mortality O
after O
administration O
of O
aprotinin O
compared O
to O
tranexamic B
acid I
in O
an O
unselected O
, O
consecutive O
cohort O
. O

METHODS O
: O
Perioperative O
data O
from O
consecutive O
cardiac O
surgery O
patients O
were O
prospectively O
collected O
between O
September O
2005 O
and O
June O
2006 O
in O
a O
university O
- O
affiliated O
clinic O
( O
n O
= O
1188 O
) O
. O

During O
the O
first O
5 O
mo O
, O
596 O
patients O
received O
aprotinin O
( O
Group O
A O
) O
; O
in O
the O
next O
5 O
mo O
, O
592 O
patients O
were O
treated O
with O
tranexamic B
acid I
( O
Group O
T O
) O
. O

Except O
for O
antifibrinolytic O
therapy O
, O
the O
anesthetic O
and O
surgical O
protocols O
remained O
unchanged O
. O

RESULTS O
: O
The O
pre O
- O
and O
intraoperative O
variables O
were O
comparable O
between O
the O
treatment O
groups O
. O

Postoperatively O
, O
a O
significantly O
higher O
incidence O
of O
seizures O
was O
found O
in O
Group O
T O
( O
4 O
. O
6 O
% O
vs O
1 O
. O
2 O
% O
, O
P O
< O
0 O
. O
001 O
) O
. O

This O
difference O
was O
also O
significant O
in O
the O
primary O
valve O
surgery O
and O
the O
high O
risk O
surgery O
subgroups O
( O
7 O
. O
9 O
% O
vs O
1 O
. O
2 O
% O
, O
P O
= O
0 O
. O
003 O
; O
7 O
. O
3 O
% O
vs O
2 O
. O
4 O
% O
, O
P O
= O
0 O
. O
035 O
, O
respectively O
) O
. O

Persistent O
atrial O
fibrillation O
( O
7 O
. O
9 O
% O
vs O
2 O
. O
3 O
% O
, O
P O
= O
0 O
. O
020 O
) O
and O
renal O
failure O
( O
9 O
. O
7 O
% O
vs O
1 O
. O
7 O
% O
, O
P O
= O
0 O
. O
002 O
) O
were O
also O
more O
common O
in O
Group O
T O
, O
in O
the O
primary O
valve O
surgery O
subgroup O
. O

On O
the O
contrary O
, O
among O
primary O
coronary O
artery O
bypass O
surgery O
patients O
, O
there O
were O
more O
acute O
myocardial O
infarctions O
and O
renal O
dysfunction O
in O
Group O
A O
( O
5 O
. O
8 O
% O
vs O
2 O
. O
0 O
% O
, O
P O
= O
0 O
. O
027 O
; O
22 O
. O
5 O
% O
vs O
15 O
. O
2 O
% O
, O
P O
= O
0 O
. O
036 O
, O
respectively O
) O
. O

The O
1 O
- O
yr O
mortality O
was O
significantly O
higher O
after O
aprotinin O
treatment O
in O
the O
high O
risk O
surgery O
group O
( O
17 O
. O
7 O
% O
vs O
9 O
. O
8 O
% O
, O
P O
= O
0 O
. O
034 O
) O
. O

CONCLUSION O
: O
Both O
antifibrinolytic O
drugs O
bear O
the O
risk O
of O
adverse O
outcome O
depending O
on O
the O
type O
of O
cardiac O
surgery O
. O

Administration O
of O
aprotinin O
should O
be O
avoided O
in O
coronary O
artery O
bypass O
graft O
and O
high O
risk O
patients O
, O
whereas O
administration O
of O
tranexamic B
acid I
is O
not O
recommended O
in O
valve O
surgery O
. O

Delirium O
in O
an O
elderly O
woman O
possibly O
associated O
with O
administration O
of O
misoprostol B
. O

Misoprostol B
has O
been O
associated O
with O
adverse O
reactions O
, O
including O
gastrointestinal O
symptoms O
, O
gynecologic O
problems O
, O
and O
headache O
. O

Changes O
in O
mental O
status O
, O
however O
, O
have O
not O
been O
reported O
. O

We O
present O
a O
case O
in O
which O
an O
89 O
- O
year O
- O
old O
woman O
in O
a O
long O
- O
term O
care O
facility O
became O
confused O
after O
the O
initiation O
of O
misoprostol B
therapy O
. O

The O
patient O
' O
s O
change O
in O
mental O
status O
was O
first O
reported O
nine O
days O
after O
the O
initiation O
of O
therapy O
. O

Her O
delirium O
significantly O
improved O
after O
misoprostol B
was O
discontinued O
and O
her O
mental O
status O
returned O
to O
normal O
within O
a O
week O
. O

Because O
no O
other O
factors O
related O
to O
this O
patient O
changed O
significantly O
, O
the O
delirium O
experienced O
by O
this O
patient O
possibly O
resulted O
from O
misoprostol B
therapy O
. O

The O
biological O
properties O
of O
the O
optical O
isomers O
of O
propranolol B
and O
their O
effects O
on O
cardiac O
arrhythmias O
. O

1 O
. O

The O
optical O
isomers O
of O
propranolol B
have O
been O
compared O
for O
their O
beta O
- O
blocking O
and O
antiarrhythmic O
activities O
. O
2 O
. O

In O
blocking O
the O
positive O
inotropic O
and O
chronotropic O
responses O
to O
isoprenaline B
, O
( O
+ O
) O
- O
propranolol B
had O
less O
than O
one O
hundredth O
the O
potency O
of O
( O
- O
) O
- O
propranolol B
. O

At O
dose O
levels O
of O
( O
+ O
) O
- O
propranolol B
which O
attenuated O
the O
responses O
to O
isoprenaline B
, O
there O
was O
a O
significant O
prolongation O
of O
the O
PR O
interval O
of O
the O
electrocardiogram O
. O
3 O
. O

The O
metabolic O
responses O
to O
isoprenaline B
in O
dogs O
( O
an O
increase O
in O
circulating O
glucose B
, O
lactate B
and O
free O
fatty B
acids I
) O
were O
all O
blocked O
by O
( O
- O
) O
- O
propranolol B
. O

( O
+ O
) O
- O
Propranolol B
had O
no O
effect O
on O
fatty O
acid O
mobilization O
but O
significantly O
reduced O
the O
increments O
in O
both O
lactate B
and O
glucose B
. O
4 O
. O

Both O
isomers O
of O
propranolol B
possessed O
similar O
depressant O
potency O
on O
isolated O
atrial O
muscle O
taken O
from O
guinea O
- O
pigs O
. O
5 O
. O

The O
isomers O
of O
propranolol B
exhibited O
similar O
local O
anaesthetic O
potencies O
on O
an O
isolated O
frog O
nerve O
preparation O
at O
a O
level O
approximately O
three O
times O
that O
of O
procaine B
. O

The O
racemic O
compound O
was O
significantly O
less O
potent O
than O
either O
isomer O
. O
6 O
. O

Both O
isomers O
of O
propranolol B
were O
capable O
of O
preventing O
adrenaline B
- O
induced O
cardiac O
arrhythmias O
in O
cats O
anaesthetized O
with O
halothane B
, O
but O
the O
mean O
dose O
of O
( O
- O
) O
- O
propranolol B
was O
0 O
. O
09 O
+ O
/ O
- O
0 O
. O
02 O
mg O
/ O
kg O
whereas O
that O
of O
( O
+ O
) O
- O
propranolol B
was O
4 O
. O
2 O
+ O
/ O
- O
1 O
. O
2 O
mg O
/ O
kg O
. O

At O
the O
effective O
dose O
level O
of O
( O
+ O
) O
- O
propranolol B
there O
was O
a O
significant O
prolongation O
of O
the O
PR O
interval O
of O
the O
electrocardiogram O
. O

Blockade O
of O
arrhythmias O
with O
both O
isomers O
was O
surmountable O
by O
increasing O
the O
dose O
of O
adrenaline B
. O
7 O
. O

Both O
isomers O
of O
propranolol B
were O
also O
capable O
of O
reversing O
ventricular O
tachycardia O
caused O
by O
ouabain B
in O
anaesthetized O
cats O
and O
dogs O
. O

The O
dose O
of O
( O
- O
) O
- O
propranolol B
was O
significantly O
smaller O
than O
that O
of O
( O
+ O
) O
- O
propranolol B
in O
both O
species O
but O
much O
higher O
than O
that O
required O
to O
produce O
evidence O
of O
beta O
- O
blockade O
. O
8 O
. O

The O
implications O
of O
these O
results O
are O
discussed O
. O

Topotecan B
in O
combination O
with O
radiotherapy O
in O
unresectable O
glioblastoma O
: O
a O
phase O
2 O
study O
. O

Improving O
glioblastoma O
multiforme O
( O
GBM O
) O
treatment O
with O
radio O
- O
chemotherapy O
remains O
a O
challenge O
. O

Topotecan B
is O
an O
attractive O
option O
as O
it O
exhibits O
growth O
inhibition O
of O
human O
glioma O
as O
well O
as O
brain O
penetration O
. O

The O
present O
study O
assessed O
the O
combination O
of O
radiotherapy O
( O
60 O
Gy O
/ O
30 O
fractions O
/ O
40 O
days O
) O
and O
topotecan B
( O
0 O
. O
9 O
mg O
/ O
m O
( O
2 O
) O
/ O
day O
on O
days O
1 O
- O
5 O
on O
weeks O
1 O
, O
3 O
and O
5 O
) O
in O
50 O
adults O
with O
histologically O
proven O
and O
untreated O
GBM O
. O

The O
incidence O
of O
non O
- O
hematological O
toxicities O
was O
low O
and O
grade O
3 O
- O
4 O
hematological O
toxicities O
were O
reported O
in O
20 O
patients O
( O
mainly O
lymphopenia O
and O
neutropenia O
) O
. O

Partial O
response O
and O
stabilization O
rates O
were O
2 O
% O
and O
32 O
% O
, O
respectively O
, O
with O
an O
overall O
time O
to O
progression O
of O
12 O
weeks O
. O

One O
- O
year O
overall O
survival O
( O
OS O
) O
rate O
was O
42 O
% O
, O
with O
a O
median O
OS O
of O
40 O
weeks O
. O

Topotecan B
in O
combination O
with O
radiotherapy O
was O
well O
tolerated O
. O

However O
, O
while O
response O
and O
stabilization O
concerned O
one O
- O
third O
of O
the O
patients O
, O
the O
study O
did O
not O
show O
increased O
benefits O
in O
terms O
of O
survival O
in O
patients O
with O
unresectable O
GBM O
. O

Long O
- O
term O
lithium B
therapy O
leading O
to O
hyperparathyroidism O
: O
a O
case O
report O
. O

PURPOSE O
: O
This O
paper O
reviews O
the O
effect O
of O
chronic O
lithium B
therapy O
on O
serum O
calcium B
level O
and O
parathyroid O
glands O
, O
its O
pathogenesis O
, O
and O
treatment O
options O
. O

We O
examined O
the O
case O
of O
a O
lithium B
- O
treated O
patient O
who O
had O
recurrent O
hypercalcemia O
to O
better O
understand O
the O
disease O
process O
. O

CONCLUSION O
: O
Primary O
hyperparathyroidism O
is O
a O
rare O
but O
potentially O
life O
- O
threatening O
side O
effect O
of O
long O
- O
term O
lithium B
therapy O
. O

Careful O
patient O
selection O
and O
long O
- O
term O
follow O
- O
up O
can O
reduce O
morbidity O
. O

PRACTICAL O
IMPLICATIONS O
: O
As O
much O
as O
15 O
% O
of O
lithium B
- O
treated O
patients O
become O
hypercalcemic O
. O

By O
routinely O
monitoring O
serum O
calcium B
levels O
, O
healthcare O
providers O
can O
improve O
the O
quality O
of O
life O
of O
this O
patient O
group O
. O

Comparison O
of O
laryngeal O
mask O
with O
endotracheal O
tube O
for O
anesthesia O
in O
endoscopic O
sinus O
surgery O
. O

BACKGROUND O
: O
The O
purpose O
of O
this O
study O
was O
to O
compare O
surgical O
conditions O
, O
including O
the O
amount O
of O
intraoperative O
bleeding O
as O
well O
as O
intraoperative O
blood O
pressure O
, O
during O
functional O
endoscopic O
sinus O
surgery O
( O
FESS O
) O
using O
flexible O
reinforced O
laryngeal O
mask O
airway O
( O
FRLMA O
) O
versus O
endotracheal O
tube O
( O
ETT O
) O
in O
maintaining O
controlled O
hypotension O
anesthesia O
induced O
by O
propofol B
- O
remifentanil B
total O
i O
. O
v O
. O
anesthesia O
( O
TIVA O
) O
. O

METHODS O
: O
Sixty O
normotensive O
American O
Society O
of O
Anesthesiologists O
I O
- O
II O
adult O
patients O
undergoing O
FESS O
under O
controlled O
hypotension O
anesthesia O
caused O
by O
propofol B
- O
remifentanil B
- O
TIVA O
were O
randomly O
assigned O
into O
two O
groups O
: O
group O
I O
, O
FRLMA O
; O
group O
II O
, O
ETT O
. O

Hemorrhage O
was O
measured O
and O
the O
visibility O
of O
the O
operative O
field O
was O
evaluated O
according O
to O
a O
six O
- O
point O
scale O
. O

RESULTS O
: O
Controlled O
hypotension O
was O
achieved O
within O
a O
shorter O
period O
using O
laryngeal O
mask O
using O
lower O
rates O
of O
remifentanil B
infusion O
and O
lower O
total O
dose O
of O
remifentanil B
. O

CONCLUSION O
: O
In O
summary O
, O
our O
results O
indicate O
that O
airway O
management O
using O
FRLMA O
during O
controlled O
hypotension O
anesthesia O
provided O
better O
surgical O
conditions O
in O
terms O
of O
quality O
of O
operative O
field O
and O
blood O
loss O
and O
allowed O
for O
convenient O
induced O
hypotension O
with O
low O
doses O
of O
remifentanil B
during O
TIVA O
in O
patients O
undergoing O
FESS O
. O

Nonalcoholic O
fatty O
liver O
disease O
during O
valproate B
therapy O
. O

Valproic B
acid I
( O
VPA B
) O
is O
effective O
for O
the O
treatment O
of O
many O
types O
of O
epilepsy O
, O
but O
its O
use O
can O
be O
associated O
with O
an O
increase O
in O
body O
weight O
. O

We O
report O
a O
case O
of O
nonalcoholic O
fatty O
liver O
disease O
( O
NAFLD O
) O
arising O
in O
a O
child O
who O
developed O
obesity O
during O
VPA B
treatment O
. O

Laboratory O
data O
revealed O
hyperinsulinemia O
with O
insulin O
resistance O
. O

After O
the O
withdrawal O
of O
VPA B
therapy O
, O
our O
patient O
showed O
a O
significant O
weight O
loss O
, O
a O
decrease O
of O
body O
mass O
index O
, O
and O
normalization O
of O
metabolic O
and O
endocrine O
parameters O
; O
moreover O
, O
ultrasound O
measurements O
showed O
a O
complete O
normalization O
. O

The O
present O
case O
suggests O
that O
obesity O
, O
hyperinsulinemia O
, O
insulin O
resistance O
, O
and O
long O
- O
term O
treatment O
with O
VPA B
may O
be O
all O
associated O
with O
the O
development O
of O
NAFLD O
; O
this O
side O
effect O
is O
reversible O
after O
VPA B
withdrawal O
. O

Carbimazole B
induced O
ANCA O
positive O
vasculitis O
. O

Anti O
- O
thyroid O
drugs O
, O
like O
carbimazole B
and O
propylthiouracil B
( O
PTU B
) O
are O
commonly O
prescribed O
for O
the O
treatment O
of O
hyperthyroidism O
. O

One O
should O
be O
aware O
of O
the O
side O
effects O
of O
antithyroid O
medications O
. O

Antineutrophil O
cytoplasmic O
antibody O
( O
ANCA O
) O
- O
- O
associated O
vasculitis O
is O
a O
potentially O
life O
- O
threatening O
adverse O
effect O
of O
antithyroidmedications O
. O

We O
report O
a O
patient O
with O
Graves O
' O
disease O
who O
developed O
ANCA O
positive O
carbimazole B
induced O
vasculitis O
. O

The O
episode O
was O
characterized O
by O
a O
vasculitic O
skin O
rash O
associated O
with O
large O
joint O
arthritis O
, O
pyrexia O
and O
parotiditis O
but O
no O
renal O
or O
pulmonary O
involvement O
. O

He O
was O
referred O
to O
us O
for O
neurological O
evaluation O
because O
he O
had O
difficulty O
in O
getting O
up O
from O
squatting O
position O
and O
was O
suspected O
to O
have O
myositis O
. O

Carbimazole B
and O
methimazole B
have O
a O
lower O
incidence O
of O
reported O
ANCA O
positive O
side O
effects O
than O
PUT B
. O

To O
the O
best O
of O
our O
knowledge O
this O
is O
the O
first O
ANCA O
positive O
carbimazole B
induced O
vasculitis O
case O
reported O
from O
India O
. O

Aspirin B
for O
the O
primary O
prevention O
of O
cardiovascular O
events O
: O
an O
update O
of O
the O
evidence O
for O
the O
U O
. O
S O
. O

Preventive O
Services O
Task O
Force O
. O

BACKGROUND O
: O
Coronary O
heart O
disease O
and O
cerebrovascular O
disease O
are O
leading O
causes O
of O
death O
in O
the O
United O
States O
. O

In O
2002 O
, O
the O
U O
. O
S O
. O

Preventive O
Services O
Task O
Force O
( O
USPSTF O
) O
strongly O
recommended O
that O
clinicians O
discuss O
aspirin B
with O
adults O
who O
are O
at O
increased O
risk O
for O
coronary O
heart O
disease O
. O

PURPOSE O
: O
To O
determine O
the O
benefits O
and O
harms O
of O
taking O
aspirin B
for O
the O
primary O
prevention O
of O
myocardial O
infarctions O
, O
strokes O
, O
and O
death O
. O

DATA O
SOURCES O
: O
MEDLINE O
and O
Cochrane O
Library O
( O
search O
dates O
, O
1 O
January O
2001 O
to O
28 O
August O
2008 O
) O
, O
recent O
systematic O
reviews O
, O
reference O
lists O
of O
retrieved O
articles O
, O
and O
suggestions O
from O
experts O
. O

STUDY O
SELECTION O
: O
English O
- O
language O
randomized O
, O
controlled O
trials O
( O
RCTs O
) O
; O
case O
- O
control O
studies O
; O
meta O
- O
analyses O
; O
and O
systematic O
reviews O
of O
aspirin B
versus O
control O
for O
the O
primary O
prevention O
of O
cardiovascular O
disease O
( O
CVD O
) O
were O
selected O
to O
answer O
the O
following O
questions O
: O
Does O
aspirin B
decrease O
coronary O
heart O
events O
, O
strokes O
, O
death O
from O
coronary O
heart O
events O
or O
stroke O
, O
or O
all O
- O
cause O
mortality O
in O
adults O
without O
known O
CVD O
? O

Does O
aspirin B
increase O
gastrointestinal O
bleeding O
or O
hemorrhagic O
strokes O
? O

DATA O
EXTRACTION O
: O
All O
studies O
were O
reviewed O
, O
abstracted O
, O
and O
rated O
for O
quality O
by O
using O
predefined O
USPSTF O
criteria O
. O

DATA O
SYNTHESIS O
: O
New O
evidence O
from O
1 O
good O
- O
quality O
RCT O
, O
1 O
good O
- O
quality O
meta O
- O
analysis O
, O
and O
2 O
fair O
- O
quality O
subanalyses O
of O
RCTs O
demonstrates O
that O
aspirin B
use O
reduces O
the O
number O
of O
CVD O
events O
in O
patients O
without O
known O
CVD O
. O

Men O
in O
these O
studies O
experienced O
fewer O
myocardial O
infarctions O
and O
women O
experienced O
fewer O
ischemic O
strokes O
. O

Aspirin B
does O
not O
seem O
to O
affect O
CVD O
mortality O
or O
all O
- O
cause O
mortality O
in O
either O
men O
or O
women O
. O

The O
use O
of O
aspirin B
for O
primary O
prevention O
increases O
the O
risk O
for O
major O
bleeding O
events O
, O
primarily O
gastrointestinal O
bleeding O
events O
, O
in O
both O
men O
and O
women O
. O

Men O
have O
an O
increased O
risk O
for O
hemorrhagic O
strokes O
with O
aspirin B
use O
. O

A O
new O
RCT O
and O
meta O
- O
analysis O
suggest O
that O
the O
risk O
for O
hemorrhagic O
strokes O
in O
women O
is O
not O
statistically O
significantly O
increased O
. O

LIMITATIONS O
: O
New O
evidence O
on O
aspirin B
for O
the O
primary O
prevention O
of O
CVD O
is O
limited O
. O

The O
dose O
of O
aspirin B
used O
in O
the O
RCTs O
varied O
, O
which O
prevented O
the O
estimation O
of O
the O
most O
appropriate O
dose O
for O
primary O
prevention O
. O

Several O
of O
the O
RCTs O
were O
conducted O
within O
populations O
of O
health O
professionals O
, O
which O
potentially O
limits O
generalizability O
. O

CONCLUSION O
: O
Aspirin B
reduces O
the O
risk O
for O
myocardial O
infarction O
in O
men O
and O
strokes O
in O
women O
. O

Aspirin B
use O
increases O
the O
risk O
for O
serious O
bleeding O
events O
. O

Reducing O
harm O
associated O
with O
anticoagulation O
: O
practical O
considerations O
of O
argatroban B
therapy O
in O
heparin B
- O
induced O
thrombocytopenia O
. O

Argatroban B
is O
a O
hepatically O
metabolized O
, O
direct O
thrombin O
inhibitor O
used O
for O
prophylaxis O
or O
treatment O
of O
thrombosis O
in O
heparin B
- O
induced O
thrombocytopenia O
( O
HIT O
) O
and O
for O
patients O
with O
or O
at O
risk O
of O
HIT O
undergoing O
percutaneous O
coronary O
intervention O
( O
PCI O
) O
. O

The O
objective O
of O
this O
review O
is O
to O
summarize O
practical O
considerations O
of O
argatroban B
therapy O
in O
HIT O
. O

The O
US O
FDA O
- O
recommended O
argatroban B
dose O
in O
HIT O
is O
2 O
microg O
/ O
kg O
/ O
min O
( O
reduced O
in O
patients O
with O
hepatic O
impairment O
and O
in O
paediatric O
patients O
) O
, O
adjusted O
to O
achieve O
activated O
partial O
thromboplastin O
times O
( O
aPTTs O
) O
1 O
. O
5 O
- O
3 O
times O
baseline O
( O
not O
> O
100 O
seconds O
) O
. O

Contemporary O
experiences O
indicate O
that O
reduced O
doses O
are O
also O
needed O
in O
patients O
with O
conditions O
associated O
with O
hepatic O
hypoperfusion O
, O
e O
. O
g O
. O
heart O
failure O
, O
yet O
are O
unnecessary O
for O
renal O
dysfunction O
, O
adult O
age O
, O
sex O
, O
race O
/ O
ethnicity O
or O
obesity O
. O

Argatroban B
0 O
. O
5 O
- O
1 O
. O
2 O
microg O
/ O
kg O
/ O
min O
typically O
supports O
therapeutic O
aPTTs O
. O

The O
FDA O
- O
recommended O
dose O
during O
PCI O
is O
25 O
microg O
/ O
kg O
/ O
min O
( O
350 O
microg O
/ O
kg O
initial O
bolus O
) O
, O
adjusted O
to O
achieve O
activated O
clotting O
times O
( O
ACTs O
) O
of O
300 O
- O
450 O
sec O
. O

For O
PCI O
, O
argatroban B
has O
not O
been O
investigated O
in O
hepatically O
impaired O
patients O
; O
dose O
adjustment O
is O
unnecessary O
for O
adult O
age O
, O
sex O
, O
race O
/ O
ethnicity O
or O
obesity O
, O
and O
lesser O
doses O
may O
be O
adequate O
with O
concurrent O
glycoprotein O
IIb O
/ O
IIIa O
inhibition O
. O

Argatroban B
prolongs O
the O
International O
Normalized O
Ratio O
, O
and O
published O
approaches O
for O
monitoring O
the O
argatroban B
- O
to O
- O
warfarin B
transition O
should O
be O
followed O
. O

Major O
bleeding O
with O
argatroban B
is O
0 O
- O
10 O
% O
in O
the O
non O
- O
interventional O
setting O
and O
0 O
- O
5 O
. O
8 O
% O
periprocedurally O
. O

Argatroban B
has O
no O
specific O
antidote O
, O
and O
if O
excessive O
anticoagulation O
occurs O
, O
argatroban B
infusion O
should O
be O
stopped O
or O
reduced O
. O

Improved O
familiarity O
of O
healthcare O
professionals O
with O
argatroban B
therapy O
in O
HIT O
, O
including O
in O
special O
populations O
and O
during O
PCI O
, O
may O
facilitate O
reduction O
of O
harm O
associated O
with O
HIT O
( O
e O
. O
g O
. O
fewer O
thromboses O
) O
or O
its O
treatment O
( O
e O
. O
g O
. O
fewer O
argatroban B
medication O
errors O
) O
. O

Rhabdomyolysis O
and O
brain O
ischemic O
stroke O
in O
a O
heroin B
- O
dependent O
male O
under O
methadone B
maintenance O
therapy O
. O

OBJECTIVE O
: O
There O
are O
several O
complications O
associated O
with O
heroin O
abuse O
, O
some O
of O
which O
are O
life O
- O
threatening O
. O

Methadone B
may O
aggravate O
this O
problem O
. O

METHOD O
: O
A O
clinical O
case O
description O
. O

RESULTS O
: O
A O
33 O
- O
year O
- O
old O
man O
presented O
with O
rhabdomyolysis O
and O
cerebral O
ischemic O
stroke O
after O
intravenous O
heroin B
. O

He O
had O
used O
heroin B
since O
age O
20 O
, O
and O
had O
used O
150 O
mg O
methadone B
daily O
for O
6 O
months O
. O

He O
was O
found O
unconsciousness O
at O
home O
and O
was O
sent O
to O
our O
hospital O
. O

In O
the O
ER O
, O
his O
opiate O
level O
was O
4497 O
ng O
/ O
ml O
. O

In O
the O
ICU O
, O
we O
found O
rhabdomyolysis O
, O
acute O
renal O
failure O
and O
acute O
respiratory O
failure O
. O

After O
transfer O
to O
an O
internal O
ward O
, O
we O
noted O
aphasia O
and O
weakness O
of O
his O
left O
limbs O
. O

After O
MRI O
, O
we O
found O
cerebral O
ischemic O
infarction O
. O

CONCLUSION O
: O
Those O
using O
methadone B
and O
heroin B
simultaneously O
may O
increase O
risk O
of O
rhabdomyolysis O
and O
ischemic O
stroke O
. O

Patients O
under O
methadone B
maintenance O
therapy O
should O
be O
warned O
regarding O
these O
serious O
adverse O
events O
. O

Hypotheses O
of O
heroin B
- O
related O
rhabdomyolysis O
and O
stroke O
in O
heroin B
abusers O
are O
discussed O
. O

Increased O
vulnerability O
to O
6 B
- I
hydroxydopamine I
lesion O
and O
reduced O
development O
of O
dyskinesias O
in O
mice O
lacking O
CB1 O
cannabinoid O
receptors O
. O

Motor O
impairment O
, O
dopamine B
( O
DA B
) O
neuronal O
activity O
and O
proenkephalin O
( O
PENK O
) O
gene O
expression O
in O
the O
caudate O
- O
putamen O
( O
CPu O
) O
were O
measured O
in O
6 B
- I
OHDA I
- O
lesioned O
and O
treated O
( O
L B
- I
DOPA I
+ I
benserazide I
) O
CB1 O
KO O
and O
WT O
mice O
. O

A O
lesion O
induced O
by O
6 B
- I
OHDA I
produced O
more O
severe O
motor O
deterioration O
in O
CB1 O
KO O
mice O
accompanied O
by O
more O
loss O
of O
DA B
neurons O
and O
increased O
PENK O
gene O
expression O
in O
the O
CPu O
. O

Oxidative O
/ O
nitrosative O
and O
neuroinflammatory O
parameters O
were O
estimated O
in O
the O
CPu O
and O
cingulate O
cortex O
( O
Cg O
) O
. O

CB1 O
KO O
mice O
exhibited O
higher O
MDA B
levels O
and O
iNOS O
protein O
expression O
in O
the O
CPu O
and O
Cg O
compared O
to O
WT O
mice O
. O

Treatment O
with O
L B
- I
DOPA I
+ I
benserazide I
( O
12 O
weeks O
) O
resulted O
in O
less O
severe O
dyskinesias O
in O
CB1 O
KO O
than O
in O
WT O
mice O
. O

The O
results O
revealed O
that O
the O
lack O
of O
cannabinoid O
CB1 O
receptors O
increased O
the O
severity O
of O
motor O
impairment O
and O
DA B
lesion O
, O
and O
reduced O
L B
- I
DOPA I
- O
induced O
dyskinesias O
. O

These O
results O
suggest O
that O
activation O
of O
CB1 O
receptors O
offers O
neuroprotection O
against O
dopaminergic O
lesion O
and O
the O
development O
of O
L B
- I
DOPA I
- O
induced O
dyskinesias O
. O

Hepatocellular O
oxidant O
stress O
following O
intestinal O
ischemia O
- O
reperfusion O
injury O
. O

Reperfusion O
of O
ischemic O
intestine O
results O
in O
acute O
liver O
dysfunction O
characterized O
by O
hepatocellular O
enzyme O
release O
into O
plasma O
, O
reduction O
in O
bile O
flow O
rate O
, O
and O
neutrophil O
sequestration O
within O
the O
liver O
. O

The O
pathophysiology O
underlying O
this O
acute O
hepatic O
injury O
is O
unknown O
. O

This O
study O
was O
undertaken O
to O
determine O
whether O
oxidants O
are O
associated O
with O
the O
hepatic O
injury O
and O
to O
determine O
the O
relative O
value O
of O
several O
indirect O
methods O
of O
assessing O
oxidant O
exposure O
in O
vivo O
. O

Rats O
were O
subjected O
to O
a O
standardized O
intestinal O
ischemia O
- O
reperfusion O
injury O
. O

Hepatic O
tissue O
was O
assayed O
for O
lipid O
peroxidation O
products O
and O
oxidized O
and O
reduced O
glutathione B
. O

There O
was O
no O
change O
in O
hepatic O
tissue O
total O
glutathione B
following O
intestinal O
ischemia O
- O
reperfusion O
injury O
. O

Oxidized O
glutathione B
( O
GSSG B
) O
increased O
significantly O
following O
30 O
and O
60 O
min O
of O
reperfusion O
. O

There O
was O
no O
increase O
in O
any O
of O
the O
products O
of O
lipid O
peroxidation O
associated O
with O
this O
injury O
. O

An O
increase O
in O
GSSG B
within O
hepatic O
tissue O
during O
intestinal O
reperfusion O
suggests O
exposure O
of O
hepatocytes O
to O
an O
oxidant O
stress O
. O

The O
lack O
of O
a O
significant O
increase O
in O
products O
of O
lipid O
peroxidation O
suggests O
that O
the O
oxidant O
stress O
is O
of O
insufficient O
magnitude O
to O
result O
in O
irreversible O
injury O
to O
hepatocyte O
cell O
membranes O
. O

These O
data O
also O
suggest O
that O
the O
measurement O
of O
tissue O
GSSG B
may O
be O
a O
more O
sensitive O
indicator O
of O
oxidant O
stress O
than O
measurement O
of O
products O
of O
lipid O
peroxidation O
. O

Animal O
model O
of O
mania O
induced O
by O
ouabain B
: O
Evidence O
of O
oxidative O
stress O
in O
submitochondrial O
particles O
of O
the O
rat O
brain O
. O

The O
intracerebroventricular O
( O
ICV O
) O
administration O
of O
ouabain B
( O
a O
Na B
( O
+ O
) O
/ O
K B
( O
+ O
) O
- O
ATPase O
inhibitor O
) O
in O
rats O
has O
been O
suggested O
to O
mimic O
some O
symptoms O
of O
human O
bipolar O
mania O
. O

Clinical O
studies O
have O
shown O
that O
bipolar O
disorder O
may O
be O
related O
to O
mitochondrial O
dysfunction O
. O

Herein O
, O
we O
investigated O
the O
behavioral O
and O
biochemical O
effects O
induced O
by O
the O
ICV O
administration O
of O
ouabain B
in O
rats O
. O

To O
achieve O
this O
aim O
, O
the O
effects O
of O
ouabain B
injection O
immediately O
after O
and O
7 O
days O
following O
a O
single O
ICV O
administration O
( O
at O
concentrations O
of O
10 O
( O
- O
2 O
) O
and O
10 O
( O
- O
3 O
) O
M O
) O
on O
locomotion O
was O
measured O
using O
the O
open O
- O
field O
test O
. O

Additionally O
, O
thiobarbituric B
acid I
reactive I
substances I
( O
TBARSs B
) O
and O
superoxide B
production O
were O
measured O
in O
submitochondrial O
particles O
of O
the O
prefrontal O
cortex O
, O
hippocampus O
, O
striatum O
and O
amygdala O
. O

Our O
findings O
demonstrated O
that O
ouabain B
at O
10 O
( O
- O
2 O
) O
and O
10 O
( O
- O
3 O
) O
M O
induced O
hyperlocomotion O
in O
rats O
, O
and O
this O
response O
remained O
up O
to O
7 O
days O
following O
a O
single O
ICV O
injection O
. O

In O
addition O
, O
we O
observed O
that O
the O
persistent O
increase O
in O
the O
rat O
spontaneous O
locomotion O
is O
associated O
with O
increased O
TBARS B
levels O
and O
superoxide B
generation O
in O
submitochondrial O
particles O
in O
the O
prefrontal O
cortex O
, O
striatum O
and O
amygdala O
. O

In O
conclusion O
, O
ouabain B
- O
induced O
mania O
- O
like O
behavior O
may O
provide O
a O
useful O
animal O
model O
to O
test O
the O
hypothesis O
of O
the O
involvement O
of O
oxidative O
stress O
in O
bipolar O
disorder O
. O

Intraoperative O
dialysis O
during O
liver O
transplantation O
with O
citrate B
dialysate O
. O

Liver O
transplantation O
for O
acutely O
ill O
patients O
with O
fulminant O
liver O
failure O
carries O
high O
intraoperative O
and O
immediate O
postoperative O
risks O
. O

These O
are O
increased O
with O
the O
presence O
of O
concomitant O
acute O
kidney O
injury O
( O
AKI O
) O
and O
intraoperative O
dialysis O
is O
sometimes O
required O
to O
allow O
the O
transplant O
to O
proceed O
. O

The O
derangements O
in O
the O
procoagulant O
and O
anticoagulant O
pathways O
during O
fulminant O
liver O
failure O
can O
lead O
to O
difficulties O
with O
anticoagulation O
during O
dialysis O
, O
especially O
when O
continued O
in O
the O
operating O
room O
. O

Systemic O
anticoagulation O
is O
unsafe O
and O
regional O
citrate B
anticoagulation O
in O
the O
absence O
of O
a O
functional O
liver O
carries O
the O
risk O
of O
citrate B
toxicity O
. O

Citrate B
dialysate O
, O
a O
new O
dialysate O
with O
citric B
acid I
can O
be O
used O
for O
anticoagulation O
in O
patients O
who O
cannot O
tolerate O
heparin B
or O
regional O
citrate B
. O

We O
report O
a O
case O
of O
a O
40 O
- O
year O
- O
old O
female O
with O
acetaminophen B
- O
induced O
fulminant O
liver O
failure O
with O
associated O
AKI O
who O
underwent O
intraoperative O
dialytic O
support O
during O
liver O
transplantation O
anticoagulated O
with O
citrate B
dialysate O
during O
the O
entire O
procedure O
. O

The O
patient O
tolerated O
the O
procedure O
well O
without O
any O
signs O
of O
citrate B
toxicity O
and O
maintained O
adequate O
anticoagulation O
for O
patency O
of O
the O
dialysis O
circuit O
. O

Citrate B
dialysate O
is O
a O
safe O
alternative O
for O
intradialytic O
support O
of O
liver O
transplantation O
in O
fulminant O
liver O
failure O
. O

Delirium O
in O
a O
patient O
with O
toxic O
flecainide B
plasma O
concentrations O
: O
the O
role O
of O
a O
pharmacokinetic O
drug O
interaction O
with O
paroxetine B
. O

OBJECTIVE O
: O
To O
describe O
a O
case O
of O
flecainide B
- O
induced O
delirium O
associated O
with O
a O
pharmacokinetic O
drug O
interaction O
with O
paroxetine B
. O

CASE O
SUMMARY O
: O
A O
69 O
- O
year O
- O
old O
white O
female O
presented O
to O
the O
emergency O
department O
with O
a O
history O
of O
confusion O
and O
paranoia O
over O
the O
past O
several O
days O
. O

On O
admission O
the O
patient O
was O
taking O
carvedilol B
12 O
mg O
twice O
daily O
, O
warfarin B
2 O
mg O
/ O
day O
, O
folic B
acid I
1 O
mg O
/ O
day O
, O
levothyroxine B
100 O
microg O
/ O
day O
, O
pantoprazole B
40 O
mg O
/ O
day O
, O
paroxetine B
40 O
mg O
/ O
day O
, O
and O
flecainide B
100 O
mg O
twice O
daily O
. O

Flecainide B
had O
been O
started O
2 O
weeks O
prior O
for O
atrial O
fibrillation O
. O

Laboratory O
test O
findings O
on O
admission O
were O
notable O
only O
for O
a O
flecainide B
plasma O
concentration O
of O
1360 O
microg O
/ O
L O
( O
reference O
range O
200 O
- O
1000 O
) O
. O

A O
metabolic O
drug O
interaction O
between O
flecainide B
and O
paroxetine B
, O
which O
the O
patient O
had O
been O
taking O
for O
more O
than O
5 O
years O
, O
was O
considered O
. O

Paroxetine B
was O
discontinued O
and O
the O
dose O
of O
flecainide B
was O
reduced O
to O
50 O
mg O
twice O
daily O
. O

Her O
delirium O
resolved O
3 O
days O
later O
. O

DISCUSSION O
: O
Flecainide B
and O
pharmacologically O
similar O
agents O
that O
interact O
with O
sodium B
channels O
may O
cause O
delirium O
in O
susceptible O
patients O
. O

A O
MEDLINE O
search O
( O
1966 O
- O
January O
2009 O
) O
revealed O
one O
in O
vivo O
pharmacokinetic O
study O
on O
the O
interaction O
between O
flecainide B
, O
a O
CYP2D6 O
substrate O
, O
and O
paroxetine B
, O
a O
CYP2D6 O
inhibitor O
, O
as O
well O
as O
3 O
case O
reports O
of O
flecainide B
- O
induced O
delirium O
. O

According O
to O
the O
Naranjo O
probability O
scale O
, O
flecainide B
was O
the O
probable O
cause O
of O
the O
patient O
' O
s O
delirium O
; O
the O
Horn O
Drug O
Interaction O
Probability O
Scale O
indicates O
a O
possible O
pharmacokinetic O
drug O
interaction O
between O
flecainide B
and O
paroxetine B
. O

CONCLUSIONS O
: O
Supratherapeutic O
flecainide B
plasma O
concentrations O
may O
cause O
delirium O
. O

Because O
toxicity O
may O
occur O
when O
flecainide B
is O
prescribed O
with O
paroxetine B
and O
other O
potent O
CYP2D6 O
inhibitors O
, O
flecainide B
plasma O
concentrations O
should O
be O
monitored O
closely O
with O
commencement O
of O
CYP2D6 O
inhibitors O
. O

Efficacy O
of O
everolimus B
( O
RAD001 B
) O
in O
patients O
with O
advanced O
NSCLC O
previously O
treated O
with O
chemotherapy O
alone O
or O
with O
chemotherapy O
and O
EGFR O
inhibitors O
. O

BACKGROUND O
: O
Treatment O
options O
are O
scarce O
in O
pretreated O
advanced O
non O
- O
small O
- O
cell O
lung O
cancer O
( O
NSCLC O
) O
patients O
. O

RAD001 B
, O
an O
oral O
inhibitor O
of O
the O
mammalian O
target O
of O
rapamycin B
( O
mTOR O
) O
, O
has O
shown O
phase O
I O
efficacy O
in O
NSCLC O
. O

METHODS O
: O
Stage O
IIIb O
or O
IV O
NSCLC O
patients O
, O
with O
two O
or O
fewer O
prior O
chemotherapy O
regimens O
, O
one O
platinum B
based O
( O
stratum O
1 O
) O
or O
both O
chemotherapy O
and O
epidermal O
growth O
factor O
receptor O
tyrosine B
kinase O
inhibitors O
( O
stratum O
2 O
) O
, O
received O
RAD001 B
10 O
mg O
/ O
day O
until O
progression O
or O
unacceptable O
toxicity O
. O

Primary O
objective O
was O
overall O
response O
rate O
( O
ORR O
) O
. O

Analyses O
of O
markers O
associated O
with O
the O
mTOR O
pathway O
were O
carried O
out O
on O
archival O
tumor O
from O
a O
subgroup O
using O
immunohistochemistry O
( O
IHC O
) O
and O
direct O
mutation O
sequencing O
. O

RESULTS O
: O
Eighty O
- O
five O
patients O
were O
enrolled O
, O
42 O
in O
stratum O
1 O
and O
43 O
in O
stratum O
. O

ORR O
was O
4 O
. O
7 O
% O
( O
7 O
. O
1 O
% O
stratum O
1 O
; O
2 O
. O
3 O
% O
stratum O
2 O
) O
. O

Overall O
disease O
control O
rate O
was O
47 O
. O
1 O
% O
. O

Median O
progression O
- O
free O
survivals O
( O
PFSs O
) O
were O
2 O
. O
6 O
( O
stratum O
1 O
) O
and O
2 O
. O
7 O
months O
( O
stratum O
2 O
) O
. O

Common O
> O
or O
= O
grade O
3 O
events O
were O
fatigue O
, O
dyspnea O
, O
stomatitis O
, O
anemia O
, O
and O
thrombocytopenia O
. O

Pneumonitis O
, O
probably O
or O
possibly O
related O
, O
mainly O
grade O
1 O
/ O
2 O
, O
occurred O
in O
25 O
% O
. O

Cox O
regression O
analysis O
of O
IHC O
scores O
found O
that O
only O
phospho O
AKT O
( O
pAKT O
) O
was O
a O
significant O
independent O
predictor O
of O
worse O
PFS O
. O

CONCLUSIONS O
: O
RAD001 B
10 O
mg O
/ O
day O
was O
well O
tolerated O
, O
showing O
modest O
clinical O
activity O
in O
pretreated O
NSCLC O
. O

Evaluation O
of O
RAD001 B
plus O
standard O
therapy O
for O
metastatic O
NSCLC O
continues O
. O

Posttransplant O
anemia O
: O
the O
role O
of O
sirolimus B
. O

Posttransplant O
anemia O
is O
a O
common O
problem O
that O
may O
hinder O
patients O
' O
quality O
of O
life O
. O

It O
occurs O
in O
12 O
to O
76 O
% O
of O
patients O
, O
and O
is O
most O
common O
in O
the O
immediate O
posttransplant O
period O
. O

A O
variety O
of O
factors O
have O
been O
identified O
that O
increase O
the O
risk O
of O
posttransplant O
anemia O
, O
of O
which O
the O
level O
of O
renal O
function O
is O
most O
important O
. O

Sirolimus B
, O
a O
mammalian O
target O
of O
rapamycin B
inhibitor O
, O
has O
been O
implicated O
as O
playing O
a O
special O
role O
in O
posttransplant O
anemia O
. O

This O
review O
considers O
anemia O
associated O
with O
sirolimus B
, O
including O
its O
presentation O
, O
mechanisms O
, O
and O
management O
. O

Coronary O
computerized O
tomography O
angiography O
for O
rapid O
discharge O
of O
low O
- O
risk O
patients O
with O
cocaine B
- O
associated O
chest O
pain O
. O

BACKGROUND O
: O
Most O
patients O
presenting O
to O
emergency O
departments O
( O
EDs O
) O
with O
cocaine B
- O
associated O
chest O
pain O
are O
admitted O
for O
at O
least O
12 O
hours O
and O
receive O
a O
" O
rule O
out O
acute O
coronary O
syndrome O
" O
protocol O
, O
often O
with O
noninvasive O
testing O
prior O
to O
discharge O
. O

In O
patients O
without O
cocaine B
use O
, O
coronary O
computerized O
tomography O
angiography O
( O
CTA O
) O
has O
been O
shown O
to O
be O
useful O
for O
identifying O
a O
group O
of O
patients O
at O
low O
risk O
for O
cardiac O
events O
who O
can O
be O
safely O
discharged O
. O

It O
is O
unclear O
whether O
a O
coronary O
CTA O
strategy O
would O
be O
efficacious O
in O
cocaine B
- O
associated O
chest O
pain O
, O
as O
coronary O
vasospasm O
may O
account O
for O
some O
of O
the O
ischemia O
. O

We O
studied O
whether O
a O
negative O
coronary O
CTA O
in O
patients O
with O
cocaine B
- O
associated O
chest O
pain O
could O
identify O
a O
subset O
safe O
for O
discharge O
. O

METHODS O
: O
We O
prospectively O
evaluated O
the O
safety O
of O
coronary O
CTA O
for O
low O
- O
risk O
patients O
who O
presented O
to O
the O
ED O
with O
cocaineassociated B
chest O
pain O
( O
self O
- O
reported O
or O
positive O
urine O
test O
) O
. O

Consecutive O
patients O
received O
either O
immediate O
coronary O
CTA O
in O
the O
ED O
( O
without O
serial O
markers O
) O
or O
underwent O
coronary O
CTA O
after O
a O
brief O
observation O
period O
with O
serial O
cardiac O
marker O
measurements O
. O

Patients O
with O
negative O
coronary O
CTA O
( O
maximal O
stenosis O
less O
than O
50 O
% O
) O
were O
discharged O
. O

The O
main O
outcome O
was O
30 O
- O
day O
cardiovascular O
death O
or O
myocardial O
infarction O
. O

RESULTS O
: O
A O
total O
of O
59 O
patients O
with O
cocaine B
- O
associated O
chest O
pain O
were O
evaluated O
. O

Patients O
had O
a O
mean O
age O
of O
45 O
. O
6 O
+ O
/ O
- O
6 O
. O
6 O
yrs O
and O
were O
86 O
% O
black O
, O
66 O
% O
male O
. O

Seventy O
- O
nine O
percent O
had O
a O
normal O
or O
nonspecific O
ECG O
and O
85 O
% O
had O
a O
TIMI O
score O
< O
2 O
. O

Twenty O
patients O
received O
coronary O
CTA O
immediately O
in O
the O
ED O
, O
18 O
of O
whom O
were O
discharged O
following O
CTA O
( O
90 O
% O
) O
. O

Thirty O
- O
nine O
received O
coronary O
CTA O
after O
a O
brief O
observation O
period O
, O
with O
37 O
discharged O
home O
following O
CTA O
( O
95 O
% O
) O
. O

Six O
patients O
had O
coronary O
stenosis O
> O
or O
= O
50 O
% O
. O

During O
the O
30 O
- O
day O
follow O
- O
up O
period O
, O
no O
patients O
died O
of O
a O
cardiovascular O
event O
( O
0 O
% O
; O
95 O
% O
CI O
, O
0 O
- O
6 O
. O
1 O
% O
) O
and O
no O
patient O
sustained O
a O
nonfatal O
myocardial O
infarction O
( O
0 O
% O
; O
95 O
% O
CI O
, O
0 O
- O
6 O
. O
1 O
% O
) O
. O

CONCLUSIONS O
: O
Although O
cocaine B
- O
associated O
myocardial O
ischemia O
can O
result O
from O
coronary O
vasoconstriction O
, O
patients O
with O
cocaine B
associated O
chest O
pain O
, O
a O
non O
- O
ischemic O
ECG O
, O
and O
a O
TIMI O
risk O
score O
< O
2 O
may O
be O
safely O
discharged O
from O
the O
ED O
after O
a O
negative O
coronary O
CTA O
with O
a O
low O
risk O
of O
30 O
- O
day O
adverse O
events O
. O

Bilateral O
haemorrhagic O
infarction O
of O
the O
globus O
pallidus O
after O
cocaine B
and O
alcohol B
intoxication O
. O

Cocaine B
is O
a O
risk O
factor O
for O
both O
ischemic O
and O
haemorrhagic O
stroke O
. O

We O
present O
the O
case O
of O
a O
31 O
- O
year O
- O
old O
man O
with O
bilateral O
ischemia O
of O
the O
globus O
pallidus O
after O
excessive O
alcohol B
and O
intranasal O
cocaine B
use O
. O

Drug O
- O
related O
globus O
pallidus O
infarctions O
are O
most O
often O
associated O
with O
heroin B
. O

Bilateral O
basal O
ganglia O
infarcts O
after O
the O
use O
of O
cocaine B
, O
without O
concurrent O
heroin B
use O
, O
have O
never O
been O
reported O
. O

In O
our O
patient O
, O
transient O
cardiac O
arrhythmia O
or O
respiratory O
dysfunction O
related O
to O
cocaine B
and O
/ O
or O
ethanol B
use O
were O
the O
most O
likely O
causes O
of O
cerebral O
hypoperfusion O
. O

Late O
fulminant O
posterior O
reversible O
encephalopathy O
syndrome O
after O
liver O
transplant O
. O

OBJECTIVES O
: O
Posterior O
leukoencephalopathy O
due O
to O
calcineurin O
- O
inhibitor O
- O
related O
neurotoxicity O
is O
a O
rare O
but O
severe O
complication O
that O
results O
from O
treatment O
with O
immunosuppressive O
agents O
( O
primarily O
those O
administered O
after O
a O
liver O
or O
kidney O
transplant O
) O
. O

The O
pathophysiologic O
mechanisms O
of O
that O
disorder O
remain O
unknown O
. O

CASE O
: O
We O
report O
the O
case O
of O
a O
46 O
- O
year O
- O
old O
woman O
who O
received O
a O
liver O
transplant O
in O
our O
center O
as O
treatment O
for O
alcoholic O
cirrhosis O
and O
in O
whom O
either O
a O
fulminant O
course O
of O
posterior O
leukoencephalopathy O
or O
posterior O
reversible O
encephalopathy O
syndrome O
developed O
110 O
days O
after O
transplant O
. O

After O
an O
initially O
uneventful O
course O
after O
the O
transplant O
, O
the O
patient O
rapidly O
fell O
into O
deep O
coma O
. O

RESULTS O
: O
Cerebral O
MRI O
scan O
showed O
typical O
signs O
of O
enhancement O
in O
the O
pontine O
and O
posterior O
regions O
. O

Switching O
the O
immunosuppressive O
regimen O
from O
tacrolimus B
to O
cyclosporine B
did O
not O
improve O
the O
clinical O
situation O
. O

The O
termination O
of O
treatment O
with O
any O
calcineurin O
inhibitor O
resulted O
in O
a O
complete O
resolution O
of O
that O
complication O
. O

CONCLUSIONS O
: O
Posterior O
reversible O
encephalopathy O
syndrome O
after O
liver O
transplant O
is O
rare O
. O

We O
recommend O
a O
complete O
cessation O
of O
any O
calcineurin O
inhibitor O
rather O
than O
a O
dose O
reduction O
. O

Prolonged O
hypothermia O
as O
a O
bridge O
to O
recovery O
for O
cerebral O
edema O
and O
intracranial O
hypertension O
associated O
with O
fulminant O
hepatic O
failure O
. O

BACKGROUND O
: O
To O
review O
evidence O
- O
based O
treatment O
options O
in O
patients O
with O
cerebral O
edema O
complicating O
fulminant O
hepatic O
failure O
( O
FHF O
) O
and O
discuss O
the O
potential O
applications O
of O
hypothermia O
. O

METHOD O
: O
Case O
- O
based O
observations O
from O
a O
medical O
intensive O
care O
unit O
( O
MICU O
) O
in O
a O
tertiary O
care O
facility O
in O
a O
27 O
- O
year O
- O
old O
female O
with O
FHF O
from O
acetaminophen B
and O
resultant O
cerebral O
edema O
. O

RESULTS O
: O
Our O
patient O
was O
admitted O
to O
the O
MICU O
after O
being O
found O
unresponsive O
with O
presumed O
toxicity O
from O
acetaminophen B
which O
was O
ingested O
over O
a O
2 O
- O
day O
period O
. O

The O
patient O
had O
depressed O
of O
mental O
status O
lasting O
at O
least O
24 O
h O
prior O
to O
admission O
. O

Initial O
evaluation O
confirmed O
FHF O
from O
acetaminophen B
and O
cerebral O
edema O
. O

The O
patient O
was O
treated O
with O
hyperosmolar O
therapy O
, O
hyperventilation O
, O
sedation O
, O
and O
chemical O
paralysis O
. O

Her O
intracranial O
pressure O
remained O
elevated O
despite O
maximal O
medical O
therapy O
. O

We O
then O
initiated O
therapeutic O
hypothermia O
which O
was O
continued O
for O
5 O
days O
. O

At O
re O
- O
warming O
, O
patient O
had O
resolution O
of O
her O
cerebral O
edema O
and O
intracranial O
hypertension O
. O

At O
discharge O
, O
she O
had O
complete O
recovery O
of O
neurological O
and O
hepatic O
functions O
. O

CONCLUSION O
: O
In O
patients O
with O
FHF O
and O
cerebral O
edema O
from O
acetaminophen B
overdose O
, O
prolonged O
therapeutic O
hypothermia O
could O
potentially O
be O
used O
as O
a O
life O
saving O
therapy O
and O
a O
bridge O
to O
hepatic O
and O
neurological O
recovery O
. O

A O
clinical O
trial O
of O
hypothermia O
in O
patients O
with O
this O
condition O
is O
warranted O
. O

Binasal O
visual O
field O
defects O
are O
not O
specific O
to O
vigabatrin B
. O

This O
study O
investigated O
the O
visual O
defects O
associated O
with O
the O
antiepileptic O
drug O
vigabatrin B
( O
VGB B
) O
. O

Two O
hundred O
four O
people O
with O
epilepsy O
were O
grouped O
on O
the O
basis O
of O
antiepileptic O
drug O
therapy O
( O
current O
, O
previous O
, O
or O
no O
exposure O
to O
VGB B
) O
. O

Groups O
were O
matched O
with O
respect O
to O
age O
, O
gender O
, O
and O
seizure O
frequency O
. O

All O
patients O
underwent O
objective O
assessment O
of O
electrophysiological O
function O
( O
wide O
- O
field O
multifocal O
electroretinography O
) O
and O
conventional O
visual O
field O
testing O
( O
static O
perimetry O
) O
. O

Bilateral O
visual O
field O
constriction O
was O
observed O
in O
59 O
% O
of O
patients O
currently O
taking O
VGB B
, O
43 O
% O
of O
patients O
who O
previously O
took O
VGB B
, O
and O
24 O
% O
of O
patients O
with O
no O
exposure O
to O
VGB B
. O

Assessment O
of O
retinal O
function O
revealed O
abnormal O
responses O
in O
48 O
% O
of O
current O
VGB B
users O
and O
22 O
% O
of O
prior O
VGB B
users O
, O
but O
in O
none O
of O
the O
patients O
without O
previous O
exposure O
to O
VGB B
. O

Bilateral O
visual O
field O
abnormalities O
are O
common O
in O
the O
treated O
epilepsy O
population O
, O
irrespective O
of O
drug O
history O
. O

Assessment O
by O
conventional O
static O
perimetry O
may O
neither O
be O
sufficiently O
sensitive O
nor O
specific O
to O
reliably O
identify O
retinal O
toxicity O
associated O
with O
VGB B
. O

Smoking O
of O
crack B
cocaine I
as O
a O
risk O
factor O
for O
HIV O
infection O
among O
people O
who O
use O
injection O
drugs O
. O

BACKGROUND O
: O
Little O
is O
known O
about O
the O
possible O
role O
that O
smoking O
crack B
cocaine I
has O
on O
the O
incidence O
of O
HIV O
infection O
. O

Given O
the O
increasing O
use O
of O
crack B
cocaine I
, O
we O
sought O
to O
examine O
whether O
use O
of O
this O
illicit O
drug O
has O
become O
a O
risk O
factor O
for O
HIV O
infection O
. O

METHODS O
: O
We O
included O
data O
from O
people O
participating O
in O
the O
Vancouver O
Injection O
Drug O
Users O
Study O
who O
reported O
injecting O
illicit O
drugs O
at O
least O
once O
in O
the O
month O
before O
enrolment O
, O
lived O
in O
the O
greater O
Vancouver O
area O
, O
were O
HIV O
- O
negative O
at O
enrolment O
and O
completed O
at O
least O
1 O
follow O
- O
up O
study O
visit O
. O

To O
determine O
whether O
the O
risk O
of O
HIV O
seroconversion O
among O
daily O
smokers O
of O
crack B
cocaine I
changed O
over O
time O
, O
we O
used O
Cox O
proportional O
hazards O
regression O
and O
divided O
the O
study O
into O
3 O
periods O
: O
May O
1 O
, O
1996 O
- O
Nov O
. O

30 O
, O
1999 O
( O
period O
1 O
) O
, O
Dec O
. O

1 O
, O
1999 O
- O
Nov O
. O

30 O
, O
2002 O
( O
period O
2 O
) O
, O
and O
Dec O
. O

1 O
, O
2002 O
- O
Dec O
. O

30 O
, O
2005 O
( O
period O
3 O
) O
. O

RESULTS O
: O
Overall O
, O
1048 O
eligible O
injection O
drug O
users O
were O
included O
in O
our O
study O
. O

Of O
these O
, O
137 O
acquired O
HIV O
infection O
during O
follow O
- O
up O
. O

The O
mean O
proportion O
of O
participants O
who O
reported O
daily O
smoking O
of O
crack B
cocaine I
increased O
from O
11 O
. O
6 O
% O
in O
period O
1 O
to O
39 O
. O
7 O
% O
in O
period O
3 O
. O

After O
adjusting O
for O
potential O
confounders O
, O
we O
found O
that O
the O
risk O
of O
HIV O
seroconversion O
among O
participants O
who O
were O
daily O
smokers O
of O
crack B
cocaine I
increased O
over O
time O
( O
period O
1 O
: O
hazard O
ratio O
[ O
HR O
] O
1 O
. O
03 O
, O
95 O
% O
confidence O
interval O
[ O
CI O
] O
0 O
. O
57 O
- O
1 O
. O
85 O
; O
period O
2 O
: O
HR O
1 O
. O
68 O
, O
95 O
% O
CI O
1 O
. O
01 O
- O
2 O
. O
80 O
; O
and O
period O
3 O
: O
HR O
2 O
. O
74 O
, O
95 O
% O
CI O
1 O
. O
06 O
- O
7 O
. O
11 O
) O
. O

INTERPRETATION O
: O
Smoking O
of O
crack B
cocaine I
was O
found O
to O
be O
an O
independent O
risk O
factor O
for O
HIV O
seroconversion O
among O
people O
who O
were O
injection O
drug O
users O
. O

This O
finding O
points O
to O
the O
urgent O
need O
for O
evidence O
- O
based O
public O
health O
initiatives O
targeted O
at O
people O
who O
smoke O
crack B
cocaine I
. O

Fluoxetine B
improves O
the O
memory O
deficits O
caused O
by O
the O
chemotherapy O
agent O
5 B
- I
fluorouracil I
. O

Cancer O
patients O
who O
have O
been O
treated O
with O
systemic O
adjuvant O
chemotherapy O
have O
described O
experiencing O
deteriorations O
in O
cognition O
. O

A O
widely O
used O
chemotherapeutic O
agent O
, O
5 B
- I
fluorouracil I
( O
5 B
- I
FU I
) O
, O
readily O
crosses O
the O
blood O
- O
brain O
barrier O
and O
so O
could O
have O
a O
direct O
effect O
on O
brain O
function O
. O

In O
particular O
this O
anti O
mitotic O
drug O
could O
reduce O
cell O
proliferation O
in O
the O
neurogenic O
regions O
of O
the O
adult O
brain O
. O

In O
contrast O
reports O
indicate O
that O
hippocampal O
dependent O
neurogenesis O
and O
cognition O
are O
enhanced O
by O
the O
SSRI B
antidepressant B
Fluoxetine B
. O

In O
this O
investigation O
the O
behavioural O
effects O
of O
chronic O
( O
two O
week O
) O
treatment O
with O
5 B
- I
FU I
and O
( O
three O
weeks O
) O
with O
Fluoxetine B
either O
separately O
or O
in O
combination O
with O
5 B
- I
FU I
were O
tested O
on O
adult O
Lister O
hooded O
rats O
. O

Behavioural O
effects O
were O
tested O
using O
a O
context O
dependent O
conditioned O
emotional O
response O
test O
( O
CER O
) O
which O
showed O
that O
animals O
treated O
with O
5 B
- I
FU I
had O
a O
significant O
reduction O
in O
freezing O
time O
compared O
to O
controls O
. O

A O
separate O
group O
of O
animals O
was O
tested O
using O
a O
hippocampal O
dependent O
spatial O
working O
memory O
test O
, O
the O
object O
location O
recognition O
test O
( O
OLR O
) O
. O

Animals O
treated O
only O
with O
5 B
- I
FU I
showed O
significant O
deficits O
in O
their O
ability O
to O
carry O
out O
the O
OLR O
task O
but O
co O
administration O
of O
Fluoxetine B
improved O
their O
performance O
. O

5 B
- I
FU I
chemotherapy O
caused O
a O
significant O
reduction O
in O
the O
number O
of O
proliferating O
cells O
in O
the O
sub O
granular O
zone O
of O
the O
dentate O
gyrus O
compared O
to O
controls O
. O

This O
reduction O
was O
eliminated O
when O
Fluoxetine B
was O
co O
administered O
with O
5 B
- I
FU I
. O

Fluoxetine B
on O
its O
own O
had O
no O
effect O
on O
proliferating O
cell O
number O
or O
behaviour O
. O

These O
findings O
suggest O
that O
5 B
- I
FU I
can O
negatively O
affect O
both O
cell O
proliferation O
and O
hippocampal O
dependent O
working O
memory O
and O
that O
these O
deficits O
can O
be O
reversed O
by O
the O
simultaneous O
administration O
of O
the O
antidepressant B
Fluoxetine B
. O

Liver O
- O
specific O
ablation O
of O
integrin O
- O
linked O
kinase O
in O
mice O
results O
in O
enhanced O
and O
prolonged O
cell O
proliferation O
and O
hepatomegaly O
after O
phenobarbital B
administration O
. O

We O
have O
recently O
demonstrated O
that O
disruption O
of O
extracellular O
matrix O
( O
ECM O
) O
/ O
integrin O
signaling O
via O
elimination O
of O
integrin O
- O
linked O
kinase O
( O
ILK O
) O
in O
hepatocytes O
interferes O
with O
signals O
leading O
to O
termination O
of O
liver O
regeneration O
. O

This O
study O
investigates O
the O
role O
of O
ILK O
in O
liver O
enlargement O
induced O
by O
phenobarbital B
( O
PB B
) O
. O

Wild O
- O
type O
( O
WT O
) O
and O
ILK O
: O
liver O
- O
/ O
- O
mice O
were O
given O
PB B
( O
0 O
. O
1 O
% O
in O
drinking O
water O
) O
for O
10 O
days O
. O

Livers O
were O
harvested O
on O
2 O
, O
5 O
, O
and O
10 O
days O
during O
PB B
administration O
. O

In O
the O
hepatocyte O
- O
specific O
ILK O
/ O
liver O
- O
/ O
- O
mice O
, O
the O
liver O
: O
body O
weight O
ratio O
was O
more O
than O
double O
as O
compared O
to O
0 O
h O
at O
day O
2 O
( O
2 O
. O
5 O
times O
) O
, O
while O
at O
days O
5 O
and O
10 O
, O
it O
was O
enlarged O
three O
times O
. O

In O
the O
WT O
mice O
, O
the O
increase O
was O
as O
expected O
from O
previous O
literature O
( O
1 O
. O
8 O
times O
) O
and O
seems O
to O
have O
leveled O
off O
after O
day O
2 O
. O

There O
were O
slightly O
increased O
proliferating O
cell O
nuclear O
antigen O
- O
positive O
cells O
in O
the O
ILK O
/ O
liver O
- O
/ O
- O
animals O
at O
day O
2 O
as O
compared O
to O
WT O
after O
PB B
administration O
. O

In O
the O
WT O
animals O
, O
the O
proliferative O
response O
had O
come O
back O
to O
normal O
by O
days O
5 O
and O
10 O
. O

Hepatocytes O
of O
the O
ILK O
/ O
liver O
- O
/ O
- O
mice O
continued O
to O
proliferate O
up O
until O
day O
10 O
. O

ILK O
/ O
liver O
- O
/ O
- O
mice O
also O
showed O
increased O
expression O
of O
key O
genes O
involved O
in O
hepatocyte O
proliferation O
at O
different O
time O
points O
during O
PB B
administration O
. O

In O
summary O
, O
ECM O
proteins O
communicate O
with O
the O
signaling O
machinery O
of O
dividing O
cells O
via O
ILK O
to O
regulate O
hepatocyte O
proliferation O
and O
termination O
of O
the O
proliferative O
response O
. O

Lack O
of O
ILK O
in O
the O
hepatocytes O
imparts O
prolonged O
proliferative O
response O
not O
only O
to O
stimuli O
related O
to O
liver O
regeneration O
but O
also O
to O
xenobiotic O
chemical O
mitogens O
, O
such O
as O
PB B
. O

Decreased O
Expression O
of O
Na B
/ O
K B
- O
ATPase O
, O
NHE3 O
, O
NBC1 O
, O
AQP1 O
and O
OAT O
in O
Gentamicin B
- O
induced O
Nephropathy O
. O

The O
present O
study O
was O
aimed O
to O
determine O
whether O
there O
is O
an O
altered O
regulation O
of O
tubular O
transporters O
in O
gentamicin B
- O
induced O
nephropathy O
. O

Sprague O
- O
Dawley O
male O
rats O
( O
200 O
~ O
250 O
g O
) O
were O
subcutaneously O
injected O
with O
gentamicin B
( O
100 O
mg O
/ O
kg O
per O
day O
) O
for O
7 O
days O
, O
and O
the O
expression O
of O
tubular O
transporters O
was O
determined O
by O
immunoblotting O
and O
immunohistochemistry O
. O

The O
mRNA O
and O
protein O
expression O
of O
OAT O
was O
also O
determined O
. O

Gentamicin B
- O
treated O
rats O
exhibited O
significantly O
decreased O
creatinine B
clearance O
along O
with O
increased O
plasma O
creatinine B
levels O
. O

Accordingly O
, O
the O
fractional O
excretion O
of O
sodium B
increased O
. O

Urine O
volume O
was O
increased O
, O
while O
urine O
osmolality O
and O
free O
water O
reabsorption O
were O
decreased O
. O

Immunoblotting O
and O
immunohistochemistry O
revealed O
decreased O
expression O
of O
Na B
( O
+ O
) O
/ O
K B
( O
+ O
) O
- O
ATPase O
, O
NHE3 O
, O
NBC1 O
, O
and O
AQP1 O
in O
the O
kidney O
of O
gentamicin B
- O
treated O
rats O
. O

The O
expression O
of O
OAT1 O
and O
OAT3 O
was O
also O
decreased O
. O

Gentamicin B
- O
induced O
nephropathy O
may O
at O
least O
in O
part O
be O
causally O
related O
with O
a O
decreased O
expression O
of O
Na B
( O
+ O
) O
/ O
K B
( O
+ O
) O
- O
ATPase O
, O
NHE3 O
, O
NBC1 O
, O
AQP1 O
and O
OAT O
. O

Acute O
renal O
failure O
after O
high O
- O
dose O
methotrexate B
therapy O
in O
a O
patient O
with O
ileostomy O
. O

High O
- O
dose O
methotrexate B
( O
HD O
- O
MTX B
) O
is O
an O
important O
treatment O
for O
Burkitt O
lymphoma O
, O
but O
can O
cause O
hepatic O
and O
renal O
toxicity O
when O
its O
clearance O
is O
delayed O
. O

We O
report O
a O
case O
of O
acute O
renal O
failure O
after O
HD O
- O
MTX B
therapy O
in O
a O
patient O
with O
ileostomy O
, O
The O
patient O
was O
a O
3 O
- O
year O
- O
old O
boy O
who O
had O
received O
a O
living O
- O
related O
liver O
transplantation O
for O
congenital O
biliary O
atresia O
. O

At O
day O
833 O
after O
the O
transplantation O
, O
he O
was O
diagnosed O
with O
PTLD O
( O
post O
- O
transplantation O
lymphoproliferative O
disorder O
, O
Burkitt O
- O
type O
malignant O
lymphoma O
) O
. O

During O
induction O
therapy O
, O
he O
suffered O
ileal O
perforation O
and O
ileostomy O
was O
performed O
. O

Subsequent O
HD O
- O
MTX B
therapy O
caused O
acute O
renal O
failure O
that O
required O
continuous O
hemodialysis O
. O

We O
supposed O
that O
intravascular O
hypovolemia O
due O
to O
substantial O
drainage O
from O
the O
ileostoma O
caused O
acute O
prerenal O
failure O
. O

After O
recovery O
of O
his O
renal O
function O
, O
we O
could O
safely O
treat O
the O
patient O
with O
HD O
- O
MTX B
therapy O
by O
controlling O
drainage O
from O
ileostoma O
with O
total O
parenteral O
nutrition O
. O

Longitudinal O
association O
of O
alcohol B
use O
with O
HIV O
disease O
progression O
and O
psychological O
health O
of O
women O
with O
HIV O
. O

We O
evaluated O
the O
association O
of O
alcohol B
consumption O
and O
depression O
, O
and O
their O
effects O
on O
HIV O
disease O
progression O
among O
women O
with O
HIV O
. O

The O
study O
included O
871 O
women O
with O
HIV O
who O
were O
recruited O
from O
1993 O
- O
1995 O
in O
four O
US O
cities O
. O

The O
participants O
had O
physical O
examination O
, O
medical O
record O
extraction O
, O
and O
venipuncture O
, O
CD4 O
+ O
T O
- O
cell O
counts O
determination O
, O
measurement O
of O
depression O
symptoms O
( O
using O
the O
self O
- O
report O
Center O
for O
Epidemiological O
Studies O
- O
Depression O
Scale O
) O
, O
and O
alcohol B
use O
assessment O
at O
enrollment O
, O
and O
semiannually O
until O
March O
2000 O
. O

Multilevel O
random O
coefficient O
ordinal O
models O
as O
well O
as O
multilevel O
models O
with O
joint O
responses O
were O
used O
in O
the O
analysis O
. O

There O
was O
no O
significant O
association O
between O
level O
of O
alcohol B
use O
and O
CD4 O
+ O
T O
- O
cell O
counts O
. O

When O
participants O
were O
stratified O
by O
antiretroviral O
therapy O
( O
ART O
) O
use O
, O
the O
association O
between O
alcohol B
and O
CD4 O
+ O
T O
- O
cell O
did O
not O
reach O
statistical O
significance O
. O

The O
association O
between O
alcohol B
consumption O
and O
depression O
was O
significant O
( O
p O
< O
0 O
. O
001 O
) O
. O

Depression O
had O
a O
significant O
negative O
effect O
on O
CD4 O
+ O
T O
- O
cell O
counts O
over O
time O
regardless O
of O
ART O
use O
. O

Our O
findings O
suggest O
that O
alcohol B
consumption O
has O
a O
direct O
association O
with O
depression O
. O

Moreover O
, O
depression O
is O
associated O
with O
HIV O
disease O
progression O
. O

Our O
findings O
have O
implications O
for O
the O
provision O
of O
alcohol B
use O
interventions O
and O
psychological O
resources O
to O
improve O
the O
health O
of O
women O
with O
HIV O
. O

Chemokine O
CCL2 O
and O
its O
receptor O
CCR2 O
are O
increased O
in O
the O
hippocampus O
following O
pilocarpine B
- O
induced O
status O
epilepticus O
. O

BACKGROUND O
: O
Neuroinflammation O
occurs O
after O
seizures O
and O
is O
implicated O
in O
epileptogenesis O
. O

CCR2 O
is O
a O
chemokine O
receptor O
for O
CCL2 O
and O
their O
interaction O
mediates O
monocyte O
infiltration O
in O
the O
neuroinflammatory O
cascade O
triggered O
in O
different O
brain O
pathologies O
. O

In O
this O
work O
CCR2 O
and O
CCL2 O
expression O
were O
examined O
following O
status O
epilepticus O
( O
SE O
) O
induced O
by O
pilocarpine B
injection O
. O

METHODS O
: O
SE O
was O
induced O
by O
pilocarpine B
injection O
. O

Control O
rats O
were O
injected O
with O
saline O
instead O
of O
pilocarpine B
. O

Five O
days O
after O
SE O
, O
CCR2 O
staining O
in O
neurons O
and O
glial O
cells O
was O
examined O
using O
imunohistochemical O
analyses O
. O

The O
number O
of O
CCR2 O
positive O
cells O
was O
determined O
using O
stereology O
probes O
in O
the O
hippocampus O
. O

CCL2 O
expression O
in O
the O
hippocampus O
was O
examined O
by O
molecular O
assay O
. O

RESULTS O
: O
Increased O
CCR2 O
was O
observed O
in O
the O
hippocampus O
after O
SE O
. O

Seizures O
also O
resulted O
in O
alterations O
to O
the O
cell O
types O
expressing O
CCR2 O
. O

Increased O
numbers O
of O
neurons O
that O
expressed O
CCR2 O
was O
observed O
following O
SE O
. O

Microglial O
cells O
were O
more O
closely O
apposed O
to O
the O
CCR2 O
- O
labeled O
cells O
in O
SE O
rats O
. O

In O
addition O
, O
rats O
that O
experienced O
SE O
exhibited O
CCR2 O
- O
labeling O
in O
populations O
of O
hypertrophied O
astrocytes O
, O
especially O
in O
CA1 O
and O
dentate O
gyrus O
. O

These O
CCR2 O
+ O
astroctytes O
were O
not O
observed O
in O
control O
rats O
. O

Examination O
of O
CCL2 O
expression O
showed O
that O
it O
was O
elevated O
in O
the O
hippocampus O
following O
SE O
. O

CONCLUSION O
: O
The O
data O
show O
that O
CCR2 O
and O
CCL2 O
are O
up O
- O
regulated O
in O
the O
hippocampus O
after O
pilocarpine B
- O
induced O
SE O
. O

Seizures O
also O
result O
in O
changes O
to O
CCR2 O
receptor O
expression O
in O
neurons O
and O
astrocytes O
. O

These O
changes O
might O
be O
involved O
in O
detrimental O
neuroplasticity O
and O
neuroinflammatory O
changes O
that O
occur O
following O
seizures O
. O

Metallothionein O
induction O
reduces O
caspase O
- O
3 O
activity O
and O
TNFalpha O
levels O
with O
preservation O
of O
cognitive O
function O
and O
intact O
hippocampal O
neurons O
in O
carmustine B
- O
treated O
rats O
. O

Hippocampal O
integrity O
is O
essential O
for O
cognitive O
functions O
. O

On O
the O
other O
hand O
, O
induction O
of O
metallothionein O
( O
MT O
) O
by O
ZnSO B
( I
4 I
) I
and O
its O
role O
in O
neuroprotection O
has O
been O
documented O
. O

The O
present O
study O
aimed O
to O
explore O
the O
effect O
of O
MT B
induction O
on O
carmustine B
( O
BCNU B
) O
- O
induced O
hippocampal O
cognitive O
dysfunction O
in O
rats O
. O

A O
total O
of O
60 O
male O
Wistar O
albino O
rats O
were O
randomly O
divided O
into O
four O
groups O
( O
15 O
/ O
group O
) O
: O
The O
control O
group O
injected O
with O
single O
doses O
of O
normal O
saline O
( O
i O
. O
c O
. O
v O
) O
followed O
24 O
h O
later O
by O
BCNU B
solvent O
( O
i O
. O
v O
) O
. O

The O
second O
group O
administered O
ZnSO B
( I
4 I
) I
( O
0 O
. O
1 O
micromol O
/ O
10 O
microl O
normal O
saline O
, O
i O
. O
c O
. O
v O
, O
once O
) O
then O
BCNU B
solvent O
( O
i O
. O
v O
) O
after O
24 O
h O
. O

Third O
group O
received O
BCNU B
( O
20 O
mg O
/ O
kg O
, O
i O
. O
v O
, O
once O
) O
24 O
h O
after O
injection O
with O
normal O
saline O
( O
i O
. O
c O
. O
v O
) O
. O

Fourth O
group O
received O
a O
single O
dose O
of O
ZnSO B
( I
4 I
) I
( O
0 O
. O
1 O
micromol O
/ O
10 O
microl O
normal O
saline O
, O
i O
. O
c O
. O
v O
) O
then O
BCNU B
( O
20 O
mg O
/ O
kg O
, O
i O
. O
v O
, O
once O
) O
after O
24 O
h O
. O

The O
obtained O
data O
revealed O
that O
BCNU B
administration O
resulted O
in O
deterioration O
of O
learning O
and O
short O
- O
term O
memory O
( O
STM O
) O
, O
as O
measured O
by O
using O
radial O
arm O
water O
maze O
, O
accompanied O
with O
decreased O
hippocampal O
glutathione B
reductase O
( O
GR O
) O
activity O
and O
reduced O
glutathione B
( O
GSH B
) O
content O
. O

Also O
, O
BCNU B
administration O
increased O
serum O
tumor O
necrosis O
factor O
- O
alpha O
( O
TNFalpha O
) O
, O
hippocampal O
MT O
and O
malondialdehyde B
( O
MDA B
) O
contents O
as O
well O
as O
caspase O
- O
3 O
activity O
in O
addition O
to O
histological O
alterations O
. O

ZnSO B
( I
4 I
) I
pretreatment O
counteracted O
BCNU B
- O
induced O
inhibition O
of O
GR O
and O
depletion O
of O
GSH B
and O
resulted O
in O
significant O
reduction O
in O
the O
levels O
of O
MDA B
and O
TNFalpha O
as O
well O
as O
the O
activity O
of O
caspase O
- O
3 O
. O

The O
histological O
features O
were O
improved O
in O
hippocampus O
of O
rats O
treated O
with O
ZnSO B
( I
4 I
) I
+ O
BCNU B
compared O
to O
only O
BCNU B
- O
treated O
animals O
. O

In O
conclusion O
, O
MT B
induction O
halts O
BCNU B
- O
induced O
hippocampal O
toxicity O
as O
it O
prevented O
GR O
inhibition O
and O
GSH B
depletion O
and O
counteracted O
the O
increased O
levels O
of O
TNFalpha O
, O
MDA B
and O
caspase O
- O
3 O
activity O
with O
subsequent O
preservation O
of O
cognition O
. O

Fatal O
carbamazepine B
induced O
fulminant O
eosinophilic O
( O
hypersensitivity O
) O
myocarditis O
: O
emphasis O
on O
anatomical O
and O
histological O
characteristics O
, O
mechanisms O
and O
genetics O
of O
drug O
hypersensitivity O
and O
differential O
diagnosis O
. O

The O
most O
severe O
adverse O
reactions O
to O
carbamazepine B
have O
been O
observed O
in O
the O
haemopoietic O
system O
, O
the O
liver O
and O
the O
cardiovascular O
system O
. O

A O
frequently O
fatal O
, O
although O
exceptionally O
rare O
side O
effect O
of O
carbamazepine B
is O
necrotizing O
eosinophilic O
( O
hypersensitivity O
) O
myocarditis O
. O

We O
report O
a O
case O
of O
hypersensitivity O
myocarditis O
secondary O
to O
administration O
of O
carbamazepine B
. O

Acute O
hypersensitivity O
myocarditis O
was O
not O
suspected O
clinically O
, O
and O
the O
diagnosis O
was O
made O
post O
- O
mortem O
. O

Histology O
revealed O
diffuse O
infiltration O
of O
the O
myocardium O
by O
eosinophils O
and O
lymphocytes O
with O
myocyte O
damage O
. O

Clinically O
, O
death O
was O
due O
to O
cardiogenic O
shock O
. O

To O
best O
of O
our O
knowledge O
this O
is O
the O
second O
case O
of O
fatal O
carbamazepine B
induced O
myocarditis O
reported O
in O
English O
literature O
. O

Neuropsychiatric O
behaviors O
in O
the O
MPTP B
marmoset O
model O
of O
Parkinson O
' O
s O
disease O
. O

OBJECTIVES O
: O
Neuropsychiatric O
symptoms O
are O
increasingly O
recognised O
as O
a O
significant O
problem O
in O
patients O
with O
Parkinson O
' O
s O
disease O
( O
PD O
) O
. O

These O
symptoms O
may O
be O
due O
to O
' O
sensitisation O
' O
following O
repeated O
levodopa B
treatment O
or O
a O
direct O
effect O
of O
dopamine B
on O
the O
disease O
state O
. O

The O
levodopa B
- O
treated O
MPTP B
- O
lesioned O
marmoset O
was O
used O
as O
a O
model O
of O
neuropsychiatric O
symptoms O
in O
PD O
patients O
. O

Here O
we O
compare O
the O
time O
course O
of O
levodopa B
- O
induced O
motor O
fluctuations O
and O
neuropsychiatric O
- O
like O
behaviors O
to O
determine O
the O
relationship O
between O
duration O
of O
treatment O
and O
onset O
of O
symptoms O
. O

METHODS O
: O
Marmosets O
were O
administered O
1 B
- I
methyl I
- I
4 I
- I
phenyl I
- I
1 I
, I
2 I
, I
3 I
, I
6 I
- I
tetrahydropyridine I
( O
2 O
. O
0 O
mg O
/ O
kg O
s O
. O
c O
. O
) O
for O
five O
days O
, O
resulting O
in O
stable O
parkinsonism O
. O

Levodopa B
( O
15 O
mg O
/ O
kg O
and O
benserazide B
, O
3 O
. O
75 O
mg O
/ O
kg O
) O
p O
. O
o O
. O

b O
. O
i O
. O
d O
, O
was O
administered O
for O
30 O
days O
. O

Animals O
were O
evaluated O
for O
parkinsonian O
disability O
, O
dyskinesia O
and O
on O
- O
time O
( O
motor O
fluctuations O
) O
and O
neuropsychiatric O
- O
like O
behaviors O
on O
Day O
0 O
( O
prior O
to O
levodopa B
) O
and O
on O
Days O
1 O
, O
7 O
, O
13 O
, O
27 O
and O
30 O
of O
treatment O
using O
post O
hoc O
DVD O
analysis O
by O
a O
trained O
rater O
, O
blind O
to O
the O
treatment O
day O
. O

RESULTS O
: O
The O
neuropsychiatric O
- O
like O
behavior O
rating O
scale O
demonstrated O
high O
interrater O
reliability O
between O
three O
trained O
raters O
of O
differing O
professional O
backgrounds O
. O

As O
anticipated O
, O
animals O
exhibited O
a O
progressive O
increase O
in O
levodopa B
- O
induced O
motor O
fluctuations O
, O
dyskinesia O
and O
wearing O
- O
off O
, O
that O
correlated O
with O
the O
duration O
of O
levodopa B
therapy O
. O

In O
contrast O
, O
levodopa B
- O
induced O
neuropsychiatric O
- O
like O
behaviors O
were O
present O
on O
Day O
1 O
of O
levodopa B
treatment O
and O
their O
severity O
did O
not O
correlate O
with O
duration O
of O
treatment O
. O

CONCLUSIONS O
: O
The O
data O
suggest O
that O
neuropsychiatric O
disorders O
in O
PD O
are O
more O
likely O
an O
interaction O
between O
levodopa B
and O
the O
disease O
state O
than O
a O
consequence O
of O
sensitisation O
to O
repeated O
dopaminergic O
therapy O
. O

Contrast O
medium O
nephrotoxicity O
after O
renal O
artery O
and O
coronary O
angioplasty O
. O

BACKGROUND O
: O
Renal O
dysfunction O
induced O
by O
iodinated O
contrast B
medium I
( O
CM B
) O
administration O
can O
minimize O
the O
benefit O
of O
the O
interventional O
procedure O
in O
patients O
undergoing O
renal O
angioplasty O
( O
PTRA O
) O
. O

PURPOSE O
: O
To O
compare O
the O
susceptibility O
to O
nephrotoxic O
effect O
of O
CM B
in O
patients O
undergoing O
PTRA O
with O
that O
of O
patients O
submitted O
to O
percutaneous O
coronary O
intervention O
( O
PCI O
) O
. O

MATERIAL O
AND O
METHODS O
: O
A O
total O
of O
33 O
patients O
successfully O
treated O
with O
PTRA O
( O
PTRA O
group O
, O
mean O
age O
70 O
+ O
/ O
- O
12 O
years O
, O
23 O
female O
, O
basal O
creatinine B
1 O
. O
46 O
+ O
/ O
- O
0 O
. O
79 O
, O
range O
0 O
. O
7 O
- O
4 O
. O
9 O
mg O
/ O
dl O
) O
were O
compared O
with O
33 O
patients O
undergoing O
successful O
PCI O
( O
PCI O
group O
) O
, O
matched O
for O
basal O
creatinine B
( O
1 O
. O
44 O
+ O
/ O
- O
0 O
. O
6 O
, O
range O
0 O
. O
7 O
- O
3 O
. O
4 O
mg O
/ O
dl O
) O
, O
gender O
, O
and O
age O
. O

In O
both O
groups O
postprocedural O
( O
48 O
h O
) O
serum O
creatinine B
was O
measured O
. O

RESULTS O
: O
Postprocedural O
creatinine B
level O
decreased O
nonsignificantly O
in O
the O
PTRA O
group O
( O
1 O
. O
46 O
+ O
/ O
- O
0 O
. O
8 O
vs O
. O
1 O
. O
34 O
+ O
/ O
- O
0 O
. O
5 O
mg O
/ O
dl O
, O
P O
= O
NS O
) O
and O
increased O
significantly O
in O
the O
PCI O
group O
( O
1 O
. O
44 O
+ O
/ O
- O
0 O
. O
6 O
vs O
. O
1 O
. O
57 O
+ O
/ O
- O
0 O
. O
7 O
mg O
/ O
dl O
, O
P O
< O
0 O
. O
02 O
) O
. O

Changes O
in O
serum O
creatinine B
after O
intervention O
( O
after O
- O
before O
) O
were O
significantly O
different O
between O
the O
PTRA O
and O
PCI O
groups O
( O
- O
0 O
. O
12 O
+ O
/ O
- O
0 O
. O
5 O
vs O
. O
0 O
. O
13 O
+ O
/ O
- O
0 O
. O
3 O
, O
P O
= O
0 O
. O
014 O
) O
. O

This O
difference O
was O
not O
related O
to O
either O
a O
different O
clinical O
risk O
profile O
or O
to O
the O
volume O
of O
CM B
administered O
. O

CONCLUSION O
: O
In O
this O
preliminary O
study O
patients O
submitted O
to O
PTRA O
showed O
a O
lower O
susceptibility O
to O
renal O
damage O
induced O
by O
CM B
administration O
than O
PCI O
patients O
. O

The O
effectiveness O
of O
PTRA B
on O
renal O
function O
seems O
to O
be O
barely O
influenced O
by O
CM B
toxicity O
. O

Diphenhydramine B
prevents O
the O
haemodynamic O
changes O
of O
cimetidine B
in O
ICU O
patients O
. O

Cimetidine B
, O
a O
histamine B
2 O
( O
H2 O
) O
antagonist O
, O
produces O
a O
decrease O
in O
arterial O
pressure O
due O
to O
vasodilatation O
, O
especially O
in O
critically O
ill O
patients O
. O

This O
may O
be O
because O
cimetidine B
acts O
as O
a O
histamine B
agonist O
. O

We O
, O
therefore O
, O
investigated O
the O
effects O
of O
the O
histamine B
1 O
( O
H1 O
) O
receptor O
antagonist O
, O
diphenhydramine B
, O
on O
the O
haemodynamic O
changes O
observed O
after O
cimetidine B
in O
ICU O
patients O
. O

Each O
patient O
was O
studied O
on O
two O
separate O
days O
. O

In O
a O
random O
fashion O
, O
they O
received O
cimetidine B
200 O
mg O
iv O
on O
one O
day O
, O
and O
on O
the O
other O
, O
a O
pretreatment O
of O
diphenhydramine B
40 O
mg O
iv O
with O
cimetidine B
200 O
mg O
iv O
. O

In O
the O
non O
- O
pretreatment O
group O
, O
mean O
arterial O
pressure O
( O
MAP O
) O
decreased O
from O
107 O
. O
4 O
+ O
/ O
- O
8 O
. O
4 O
mmHg O
to O
86 O
. O
7 O
+ O
/ O
- O
11 O
. O
4 O
mmHg O
( O
P O
less O
than O
0 O
. O
01 O
) O
two O
minutes O
after O
cimetidine B
. O

Also O
, O
systemic O
vascular O
resistance O
( O
SVR O
) O
decreased O
during O
the O
eight O
- O
minute O
observation O
period O
( O
P O
less O
than O
0 O
. O
01 O
) O
. O

In O
contrast O
, O
in O
the O
pretreatment O
group O
, O
little O
haemodynamic O
change O
was O
seen O
. O

We O
conclude O
that O
an O
H1 O
antagonist O
may O
be O
useful O
in O
preventing O
hypotension O
caused O
by O
iv O
cimetidine B
, O
since O
the O
vasodilating O
activity O
of O
cimetidine B
is O
mediated O
, O
in O
part O
, O
through O
the O
H1 O
receptor O
. O

Medical O
and O
psychiatric O
outcomes O
for O
patients O
transplanted O
for O
acetaminophen B
- O
induced O
acute O
liver O
failure O
: O
a O
case O
- O
control O
study O
. O

BACKGROUND O
: O
Acetaminophen B
- O
induced O
hepatotoxicity O
is O
the O
most O
common O
cause O
of O
acute O
liver O
failure O
( O
ALF O
) O
in O
the O
UK O
. O

Patients O
often O
consume O
the O
drug O
with O
suicidal O
intent O
or O
with O
a O
background O
of O
substance O
dependence O
. O

AIMS O
AND O
METHODS O
: O
We O
compared O
the O
severity O
of O
pretransplant O
illness O
, O
psychiatric O
co O
- O
morbidity O
, O
medical O
and O
psychosocial O
outcomes O
of O
all O
patients O
who O
had O
undergone O
liver O
transplantation O
( O
LT O
) O
emergently O
between O
1999 O
- O
2004 O
for O
acetaminophen B
- O
induced O
ALF O
( O
n O
= O
36 O
) O
with O
age O
- O
and O
sex O
- O
matched O
patients O
undergoing O
emergent O
LT O
for O
non O
- O
acetaminophen B
- O
induced O
ALF O
( O
n O
= O
35 O
) O
and O
elective O
LT O
for O
chronic O
liver O
disease O
( O
CLD O
, O
n O
= O
34 O
) O
. O

RESULTS O
: O
Acetaminophen B
- O
induced O
ALF O
patients O
undergoing O
LT O
had O
a O
greater O
severity O
of O
pre O
- O
LT O
illness O
reflected O
by O
higher O
Acute O
Physiology O
and O
Chronic O
Health O
Evaluation O
II O
scores O
and O
requirement O
for O
organ O
support O
compared O
with O
the O
other O
two O
groups O
. O

Twenty O
( O
56 O
% O
) O
acetaminophen B
- O
induced O
ALF O
patients O
had O
a O
formal O
psychiatric O
diagnosis O
before O
LT O
( O
non O
- O
acetaminophen B
- O
induced O
ALF O
= O
0 O
/ O
35 O
, O
CLD O
= O
2 O
/ O
34 O
; O
P O
< O
0 O
. O
01 O
for O
all O
) O
and O
nine O
( O
25 O
% O
) O
had O
a O
previous O
suicide O
attempt O
. O

During O
follow O
- O
up O
( O
median O
5 O
years O
) O
, O
there O
were O
no O
significant O
differences O
in O
rejection O
( O
acute O
and O
chronic O
) O
, O
graft O
failure O
or O
survival O
between O
the O
groups O
( O
acetaminophen B
- O
induced O
ALF O
1 O
year O
87 O
% O
, O
5 O
years O
75 O
% O
; O
non O
- O
acetaminophen B
- O
induced O
ALF O
88 O
% O
, O
78 O
% O
; O
CLD O
93 O
% O
, O
82 O
% O
: O
P O
> O
0 O
. O
6 O
log O
rank O
) O
. O

Two O
acetaminophen B
- O
induced O
ALF O
patients O
reattempted O
suicide O
post O
- O
LT O
( O
one O
died O
8 O
years O
post O
- O
LT O
) O
. O

CONCLUSIONS O
: O
Despite O
a O
high O
prevalence O
of O
psychiatric O
disturbance O
, O
outcomes O
for O
patients O
transplanted O
emergently O
for O
acetaminophen B
- O
induced O
ALF O
were O
comparable O
to O
those O
transplanted O
for O
non O
- O
acetaminophen B
- O
induced O
ALF O
and O
electively O
for O
CLD O
. O

Multidisciplinary O
approaches O
with O
long O
- O
term O
psychiatric O
follow O
- O
up O
may O
contribute O
to O
low O
post O
- O
transplant O
suicide O
rates O
seen O
and O
low O
rates O
of O
graft O
loss O
because O
of O
non O
- O
compliance O
. O

Antithrombotic O
drug O
use O
, O
cerebral O
microbleeds O
, O
and O
intracerebral O
hemorrhage O
: O
a O
systematic O
review O
of O
published O
and O
unpublished O
studies O
. O

BACKGROUND O
AND O
PURPOSE O
: O
Cerebral O
microbleeds O
( O
MB O
) O
are O
potential O
risk O
factors O
for O
intracerebral O
hemorrhage O
( O
ICH O
) O
, O
but O
it O
is O
unclear O
if O
they O
are O
a O
contraindication O
to O
using O
antithrombotic O
drugs O
. O

Insights O
could O
be O
gained O
by O
pooling O
data O
on O
MB O
frequency O
stratified O
by O
antithrombotic O
use O
in O
cohorts O
with O
ICH O
and O
ischemic O
stroke O
( O
IS O
) O
/ O
transient O
ischemic O
attack O
( O
TIA O
) O
. O

METHODS O
: O
We O
performed O
a O
systematic O
review O
of O
published O
and O
unpublished O
data O
from O
cohorts O
with O
stroke O
or O
TIA O
to O
compare O
the O
presence O
of O
MB O
in O
: O
( O
1 O
) O
antithrombotic O
users O
vs O
nonantithrombotic O
users O
with O
ICH O
; O
( O
2 O
) O
antithrombotic O
users O
vs O
nonusers O
with O
IS O
/ O
TIA O
; O
and O
( O
3 O
) O
ICH O
vs O
ischemic O
events O
stratified O
by O
antithrombotic O
use O
. O

We O
also O
analyzed O
published O
and O
unpublished O
follow O
- O
up O
data O
to O
determine O
the O
risk O
of O
ICH O
in O
antithrombotic O
users O
with O
MB B
. O

RESULTS O
: O
In O
a O
pooled O
analysis O
of O
1460 O
ICH O
and O
3817 O
IS O
/ O
TIA O
, O
MB O
were O
more O
frequent O
in O
ICH O
vs O
IS O
/ O
TIA O
in O
all O
treatment O
groups O
, O
but O
the O
excess O
increased O
from O
2 O
. O
8 O
( O
odds O
ratio O
; O
range O
, O
2 O
. O
3 O
- O
3 O
. O
5 O
) O
in O
nonantithrombotic O
users O
to O
5 O
. O
7 O
( O
range O
, O
3 O
. O
4 O
- O
9 O
. O
7 O
) O
in O
antiplatelet O
users O
and O
8 O
. O
0 O
( O
range O
, O
3 O
. O
5 O
- O
17 O
. O
8 O
) O
in O
warfarin B
users O
( O
P O
difference O
= O
0 O
. O
01 O
) O
. O

There O
was O
also O
an O
excess O
of O
MB O
in O
warfarin B
users O
vs O
nonusers O
with O
ICH O
( O
OR O
, O
2 O
. O
7 O
; O
95 O
% O
CI O
, O
1 O
. O
6 O
- O
4 O
. O
4 O
; O
P O
< O
0 O
. O
001 O
) O
but O
none O
in O
warfarin B
users O
with O
IS O
/ O
TIA O
( O
OR O
, O
1 O
. O
3 O
; O
95 O
% O
CI O
, O
0 O
. O
9 O
- O
1 O
. O
7 O
; O
P O
= O
0 O
. O
33 O
; O
P O
difference O
= O
0 O
. O
01 O
) O
. O

There O
was O
a O
smaller O
excess O
of O
MB O
in O
antiplatelet O
users O
vs O
nonusers O
with O
ICH O
( O
OR O
, O
1 O
. O
7 O
; O
95 O
% O
CI O
, O
1 O
. O
3 O
- O
2 O
. O
3 O
; O
P O
< O
0 O
. O
001 O
) O
, O
but O
findings O
were O
similar O
for O
antiplatelet O
users O
with O
IS O
/ O
TIA O
( O
OR O
, O
1 O
. O
4 O
; O
95 O
% O
CI O
, O
1 O
. O
2 O
- O
1 O
. O
7 O
; O
P O
< O
0 O
. O
001 O
; O
P O
difference O
= O
0 O
. O
25 O
) O
. O

In O
pooled O
follow O
- O
up O
data O
for O
768 O
antithrombotic O
users O
, O
presence O
of O
MB O
at O
baseline O
was O
associated O
with O
a O
substantially O
increased O
risk O
of O
subsequent O
ICH O
( O
OR O
, O
12 O
. O
1 O
; O
95 O
% O
CI O
, O
3 O
. O
4 O
- O
42 O
. O
5 O
; O
P O
< O
0 O
. O
001 O
) O
. O

CONCLUSIONS O
: O
The O
excess O
of O
MB O
in O
warfarin B
users O
with O
ICH O
compared O
to O
other O
groups O
suggests O
that O
MB O
increase O
the O
risk O
of O
warfarin B
- O
associated O
ICH O
. O

Limited O
prospective O
data O
corroborate O
these O
findings O
, O
but O
larger O
prospective O
studies O
are O
urgently O
required O
. O

Studies O
of O
synergy O
between O
morphine B
and O
a O
novel O
sodium B
channel O
blocker O
, O
CNSB002 B
, O
in O
rat O
models O
of O
inflammatory O
and O
neuropathic O
pain O
. O

OBJECTIVE O
: O
This O
study O
determined O
the O
antihyperalgesic O
effect O
of O
CNSB002 B
, O
a O
sodium B
channel O
blocker O
with O
antioxidant O
properties O
given O
alone O
and O
in O
combinations O
with O
morphine B
in O
rat O
models O
of O
inflammatory O
and O
neuropathic O
pain O
. O

DESIGN O
: O
Dose O
response O
curves O
for O
nonsedating O
doses O
of O
morphine B
and O
CNSB002 B
given O
intraperitoneally O
alone O
and O
together O
in O
combinations O
were O
constructed O
for O
antihyperalgesic O
effect O
using O
paw O
withdrawal O
from O
noxious O
heat O
in O
two O
rat O
pain O
models O
: O
carrageenan B
- O
induced O
paw O
inflammation O
and O
streptozotocin B
( O
STZ B
) O
- O
induced O
diabetic O
neuropathy O
. O

RESULTS O
: O
The O
maximum O
nonsedating O
doses O
were O
: O
morphine B
, O
3 O
. O
2 O
mg O
/ O
kg O
; O
CNSB002 B
10 O
. O
0 O
mg O
/ O
kg O
; O
5 O
. O
0 O
mg O
/ O
kg O
CNSB002 O
with O
morphine B
3 O
. O
2 O
mg O
/ O
kg O
in O
combination O
. O

The O
doses O
calculated O
to O
cause O
50 O
% O
reversal O
of O
hyperalgesia O
( O
ED50 O
) O
were O
7 O
. O
54 O
( O
1 O
. O
81 O
) O
and O
4 O
. O
83 O
( O
1 O
. O
54 O
) O
in O
the O
carrageenan B
model O
and O
44 O
. O
18 O
( O
1 O
. O
37 O
) O
and O
9 O
. O
14 O
( O
1 O
. O
24 O
) O
in O
the O
STZ B
- O
induced O
neuropathy O
model O
for O
CNSB002 O
and O
morphine B
, O
respectively O
( O
mg O
/ O
kg O
; O
mean O
, O
SEM O
) O
. O

These O
values O
were O
greater O
than O
the O
maximum O
nonsedating O
doses O
. O

The O
ED50 O
values O
for O
morphine B
when O
given O
in O
combination O
with O
CNSB002 B
( O
5 O
mg O
/ O
kg O
) O
were O
less O
than O
the O
maximum O
nonsedating O
dose O
: O
0 O
. O
56 O
( O
1 O
. O
55 O
) O
in O
the O
carrageenan B
model O
and O
1 O
. O
37 O
( O
1 O
. O
23 O
) O
in O
the O
neuropathy O
model O
( O
mg O
/ O
kg O
; O
mean O
, O
SEM O
) O
. O

The O
antinociception O
after O
morphine B
( O
3 O
. O
2 O
mg O
/ O
kg O
) O
was O
increased O
by O
co O
- O
administration O
with O
CNSB002 B
from O
28 O
. O
0 O
and O
31 O
. O
7 O
% O
to O
114 O
. O
6 O
and O
56 O
. O
9 O
% O
reversal O
of O
hyperalgesia O
in O
the O
inflammatory O
and O
neuropathic O
models O
, O
respectively O
( O
P O
< O
0 O
. O
01 O
; O
one O
- O
way O
analysis O
of O
variance O
- O
significantly O
greater O
than O
either O
drug O
given O
alone O
) O
. O

CONCLUSIONS O
: O
The O
maximum O
antihyperalgesic O
effect O
achievable O
with O
nonsedating O
doses O
of O
morphine B
may O
be O
increased O
significantly O
when O
the O
drug O
is O
used O
in O
combination O
with O
CNSB002 B
. O

Heparin B
- O
induced O
thrombocytopenia O
: O
a O
practical O
review O
. O

Heparin B
- O
induced O
thrombocytopenia O
( O
HIT O
) O
remains O
under O
- O
recognized O
despite O
its O
potentially O
devastating O
outcomes O
. O

It O
begins O
when O
heparin B
exposure O
stimulates O
the O
formation O
of O
heparin B
- O
platelet O
factor O
4 O
antibodies O
, O
which O
in O
turn O
triggers O
the O
release O
of O
procoagulant O
platelet O
particles O
. O

Thrombosis O
and O
thrombocytopenia O
that O
follow O
comprise O
the O
2 O
hallmark O
traits O
of O
HIT O
, O
with O
the O
former O
largely O
responsible O
for O
significant O
vascular O
complications O
. O

The O
prevalence O
of O
HIT O
varies O
among O
several O
subgroups O
, O
with O
greater O
incidence O
in O
surgical O
as O
compared O
with O
medical O
populations O
. O

HIT O
must O
be O
acknowledged O
for O
its O
intense O
predilection O
for O
thrombosis O
and O
suspected O
whenever O
thrombosis O
occurs O
after O
heparin B
exposure O
. O

Early O
recognition O
that O
incorporates O
the O
clinical O
and O
serologic O
clues O
is O
paramount O
to O
timely O
institution O
of O
treatment O
, O
as O
its O
delay O
may O
result O
in O
catastrophic O
outcomes O
. O

The O
treatment O
of O
HIT O
mandates O
an O
immediate O
cessation O
of O
all O
heparin B
exposure O
and O
the O
institution O
of O
an O
antithrombotic O
therapy O
, O
most O
commonly O
using O
a O
direct O
thrombin O
inhibitor O
. O

Current O
" O
diagnostic O
" O
tests O
, O
which O
primarily O
include O
functional O
and O
antigenic O
assays O
, O
have O
more O
of O
a O
confirmatory O
than O
diagnostic O
role O
in O
the O
management O
of O
HIT O
. O

Special O
attention O
must O
be O
paid O
to O
cardiac O
patients O
who O
are O
often O
exposed O
to O
heparin B
multiple O
times O
during O
their O
course O
of O
treatment O
. O

Direct O
thrombin O
inhibitors O
are O
appropriate O
, O
evidence O
- O
based O
alternatives O
to O
heparin B
in O
patients O
with O
a O
history O
of O
HIT O
, O
who O
need O
to O
undergo O
percutaneous O
coronary O
intervention O
. O

As O
heparin B
remains O
one O
of O
the O
most O
frequently O
used O
medications O
today O
with O
potential O
for O
HIT O
with O
every O
heparin B
exposure O
, O
a O
close O
vigilance O
of O
platelet O
counts O
must O
be O
practiced O
whenever O
heparin B
is O
initiated O
. O

Abductor O
paralysis O
after O
botox B
injection O
for O
adductor O
spasmodic O
dysphonia O
. O

OBJECTIVES O
/ O
HYPOTHESIS O
: O
Botulinum B
toxin I
( O
Botox B
) O
injections O
into O
the O
thyroarytenoid O
muscles O
are O
the O
current O
standard O
of O
care O
for O
adductor O
spasmodic O
dysphonia O
( O
ADSD O
) O
. O

Reported O
adverse O
effects O
include O
a O
period O
of O
breathiness O
, O
throat O
pain O
, O
and O
difficulty O
with O
swallowing O
liquids O
. O

Here O
we O
report O
multiple O
cases O
of O
bilateral O
abductor O
paralysis O
following O
Botox B
injections O
for O
ADSD O
, O
a O
complication O
previously O
unreported O
. O

STUDY O
DESIGN O
: O
Retrospective O
case O
series O
. O

METHODS O
: O
Patients O
that O
received O
Botox B
injections O
for O
spasmodic O
dysphonia O
between O
January O
2000 O
and O
October O
2009 O
were O
evaluated O
. O

Patients O
with O
ADSD O
were O
identified O
. O

The O
number O
of O
treatments O
received O
and O
adverse O
effects O
were O
noted O
. O

For O
patients O
with O
bilateral O
abductor O
paralysis O
, O
age O
, O
sex O
, O
paralytic O
Botox B
dose O
, O
prior O
Botox B
dose O
, O
and O
course O
following O
paralysis O
were O
noted O
. O

RESULTS O
: O
From O
a O
database O
of O
452 O
patients O
receiving O
Botox B
, O
352 O
patients O
had O
been O
diagnosed O
with O
ADSD O
. O

Of O
these O
352 O
patients O
, O
eight O
patients O
suffered O
bilateral O
abductor O
paralysis O
, O
and O
two O
suffered O
this O
complication O
twice O
. O

All O
affected O
patients O
were O
females O
over O
the O
age O
of O
50 O
years O
. O

Most O
patients O
had O
received O
treatments O
prior O
to O
abductor O
paralysis O
and O
continued O
receiving O
after O
paralysis O
. O

Seven O
patients O
recovered O
after O
a O
brief O
period O
of O
activity O
restrictions O
, O
and O
one O
underwent O
a O
tracheotomy O
. O

The O
incidence O
of O
abductor O
paralysis O
after O
Botox B
injection O
for O
ADSD O
was O
0 O
. O
34 O
% O
. O

CONCLUSIONS O
: O
Bilateral O
abductor O
paralysis O
is O
a O
rare O
complication O
of O
Botox B
injections O
for O
ADSD O
, O
causing O
difficulty O
with O
breathing O
upon O
exertion O
. O

The O
likely O
mechanism O
of O
paralysis O
is O
diffusion O
of O
Botox B
around O
the O
muscular O
process O
of O
the O
arytenoid O
to O
the O
posterior O
cricoarytenoid O
muscles O
. O

The O
paralysis O
is O
temporary O
, O
and O
watchful O
waiting O
with O
restriction O
of O
activity O
is O
the O
recommended O
management O
. O

Mitochondrial O
impairment O
contributes O
to O
cocaine B
- O
induced O
cardiac O
dysfunction O
: O
Prevention O
by O
the O
targeted O
antioxidant O
MitoQ B
. O

The O
goal O
of O
this O
study O
was O
to O
assess O
mitochondrial O
function O
and O
ROS O
production O
in O
an O
experimental O
model O
of O
cocaine B
- O
induced O
cardiac O
dysfunction O
. O

We O
hypothesized O
that O
cocaine O
abuse O
may O
lead O
to O
altered O
mitochondrial O
function O
that O
in O
turn O
may O
cause O
left O
ventricular O
dysfunction O
. O

Seven O
days O
of O
cocaine B
administration O
to O
rats O
led O
to O
an O
increased O
oxygen B
consumption O
detected O
in O
cardiac O
fibers O
, O
specifically O
through O
complex O
I O
and O
complex O
III O
. O

ROS O
levels O
were O
increased O
, O
specifically O
in O
interfibrillar O
mitochondria O
. O

In O
parallel O
there O
was O
a O
decrease O
in O
ATP B
synthesis O
, O
whereas O
no O
difference O
was O
observed O
in O
subsarcolemmal O
mitochondria O
. O

This O
uncoupling O
effect O
on O
oxidative O
phosphorylation O
was O
not O
detectable O
after O
short O
- O
term O
exposure O
to O
cocaine B
, O
suggesting O
that O
these O
mitochondrial O
abnormalities O
were O
a O
late O
rather O
than O
a O
primary O
event O
in O
the O
pathological O
response O
to O
cocaine B
. O

MitoQ B
, O
a O
mitochondrial O
- O
targeted O
antioxidant O
, O
was O
shown O
to O
completely O
prevent O
these O
mitochondrial O
abnormalities O
as O
well O
as O
cardiac O
dysfunction O
characterized O
here O
by O
a O
diastolic O
dysfunction O
studied O
with O
a O
conductance O
catheter O
to O
obtain O
pressure O
- O
volume O
data O
. O

Taken O
together O
, O
these O
results O
extend O
previous O
studies O
and O
demonstrate O
that O
cocaine B
- O
induced O
cardiac O
dysfunction O
may O
be O
due O
to O
a O
mitochondrial O
defect O
. O

Trimethoprim B
- O
induced O
immune O
hemolytic O
anemia O
in O
a O
pediatric O
oncology O
patient O
presenting O
as O
an O
acute O
hemolytic O
transfusion O
reaction O
. O

A O
10 O
- O
year O
- O
old O
male O
with O
acute O
leukemia O
presented O
with O
post O
- O
chemotherapy O
anemia O
. O

During O
red O
cell O
transfusion O
, O
he O
developed O
hemoglobinuria O
. O

Transfusion O
reaction O
workup O
was O
negative O
. O

Drug O
- O
induced O
immune O
hemolytic O
anemia O
was O
suspected O
because O
of O
positive O
direct O
antiglobulin O
test O
, O
negative O
eluate O
, O
and O
microspherocytes O
on O
smear O
pre O
- O
and O
post O
- O
transfusion O
. O

Drug O
studies O
using O
the O
indirect O
antiglobulin O
test O
were O
strongly O
positive O
with O
trimethoprim B
and O
trimethoprim B
- I
sulfamethoxazole I
but O
negative O
with O
sulfamethoxazole B
. O

The O
patient O
recovered O
after O
discontinuing O
the O
drug O
, O
with O
no O
recurrence O
in O
2 O
years O
. O

Other O
causes O
of O
anemia O
should O
be O
considered O
in O
patients O
with O
worse O
- O
than O
- O
expected O
anemia O
after O
chemotherapy O
. O

Furthermore O
, O
hemolysis O
during O
transfusion O
is O
not O
always O
a O
transfusion O
reaction O
. O

Verapamil B
stimulation O
test O
in O
hyperprolactinemia O
: O
loss O
of O
prolactin O
response O
in O
anatomic O
or O
functional O
stalk O
effect O
. O

AIM O
: O
Verapamil B
stimulation O
test O
was O
previously O
investigated O
as O
a O
tool O
for O
differential O
diagnosis O
of O
hyperprolactinemia O
, O
but O
with O
conflicting O
results O
. O

Macroprolactinemia O
was O
never O
considered O
in O
those O
previous O
studies O
. O

Here O
, O
we O
aimed O
to O
re O
- O
investigate O
the O
diagnostic O
value O
of O
verapamil B
in O
a O
population O
who O
were O
all O
screened O
for O
macroprolactinemia O
. O

Prolactin O
responses O
to O
verapamil B
in O
65 O
female O
patients O
( O
age O
: O
29 O
. O
9 O
+ O
/ O
- O
8 O
. O
1 O
years O
) O
with O
hyperprolactinemia O
were O
tested O
in O
a O
descriptive O
, O
matched O
case O
- O
control O
study O
. O

METHODS O
: O
Verapamil B
80 O
mg O
, O
p O
. O
o O
. O
was O
administered O
, O
and O
then O
PRL O
levels O
were O
measured O
at O
8th O
and O
16th O
hours O
, O
by O
immunometric O
chemiluminescence O
. O

Verapamil B
responsiveness O
was O
determined O
by O
peak O
percent O
change O
in O
basal O
prolactin O
levels O
( O
PRL O
) O
. O

RESULTS O
: O
Verapamil B
significantly O
increased O
PRL O
levels O
in O
healthy O
controls O
( O
N O
. O
8 O
, O
PRL O
: O
183 O
% O
) O
, O
macroprolactinoma O
( O
N O
. O
8 O
, O
PRL O
: O
7 O
% O
) O
, O
microprolactinoma O
( O
N O
. O
19 O
, O
PRL O
: O
21 O
% O
) O
, O
macroprolactinemia O
( O
N O
. O
23 O
, O
PRL O
: O
126 O
% O
) O
, O
but O
not O
in O
pseudoprolactinoma O
( O
N O
. O
8 O
, O
PRL O
: O
0 O
. O
8 O
% O
) O
, O
and O
risperidone B
- O
induced O
hyperprolactinemia O
( O
N O
. O
7 O

, O
PRL O
: O
3 O
% O
) O
. O

ROC O
curve O
analysis O
revealed O
that O
unresponsiveness O
to O
verapamil B
defined O
as O
PRL O
< O
7 O
% O
, O
discriminated O
anatomical O
or O
functional O
stalk O
effect O
( O
sensitivity O
: O
74 O
% O
, O
specificity O
: O
73 O
% O
, O
AUC O
: O
0 O
. O
855 O
+ O
/ O
- O
0 O
. O
04 O
, O
P O
< O
0 O
. O
001 O
, O
CI O
: O
0 O
. O
768 O
- O
0 O
. O
942 O
) O
associated O
with O
pseudoprolactinoma O
or O
risperidone B
- O
induced O
hyperprolactinemia O
, O
respectively O
. O

CONCLUSION O
: O
Verapamil B
responsiveness O
is O
not O
a O
reliable O
finding O
for O
the O
differential O
diagnosis O
of O
hyperprolactinemia O
. O

However O
, O
verapamil B
unresponsiveness O
discriminates O
stalk O
effect O
( O
i O
. O
e O
. O
, O
anatomically O
or O
functionally O
inhibited O
dopaminergic O
tonus O
) O
from O
other O
causes O
of O
hyperprolactinemia O
with O
varying O
degrees O
of O
responsiveness O
. O

Blockade O
of O
endothelial O
- O
mesenchymal O
transition O
by O
a O
Smad3 O
inhibitor O
delays O
the O
early O
development O
of O
streptozotocin B
- O
induced O
diabetic O
nephropathy O
. O

OBJECTIVE O
: O
A O
multicenter O
, O
controlled O
trial O
showed O
that O
early O
blockade O
of O
the O
renin O
- O
angiotensin B
system O
in O
patients O
with O
type O
1 O
diabetes O
and O
normoalbuminuria O
did O
not O
retard O
the O
progression O
of O
nephropathy O
, O
suggesting O
that O
other O
mechanism O
( O
s O
) O
are O
involved O
in O
the O
pathogenesis O
of O
early O
diabetic O
nephropathy O
( O
diabetic O
nephropathy O
) O
. O

We O
have O
previously O
demonstrated O
that O
endothelial O
- O
mesenchymal O
- O
transition O
( O
EndoMT O
) O
contributes O
to O
the O
early O
development O
of O
renal O
interstitial O
fibrosis O
independently O
of O
microalbuminuria O
in O
mice O
with O
streptozotocin B
( O
STZ B
) O
- O
induced O
diabetes O
. O

In O
the O
present O
study O
, O
we O
hypothesized O
that O
blocking O
EndoMT O
reduces O
the O
early O
development O
of O
diabetic O
nephropathy O
. O

RESEARCH O
DESIGN O
AND O
METHODS O
: O
EndoMT O
was O
induced O
in O
a O
mouse O
pancreatic O
microvascular O
endothelial O
cell O
line O
( O
MMEC O
) O
in O
the O
presence O
of O
advanced O
glycation I
end I
products I
( O
AGEs B
) O
and O
in O
the O
endothelial O
lineage O
- O
traceble O
mouse O
line O
Tie2 O
- O
Cre O
; O
Loxp O
- O
EGFP O
by O
administration O
of O
AGEs B
, O
with O
nonglycated O
mouse O
albumin O
serving O
as O
a O
control O
. O

Phosphorylated O
Smad3 O
was O
detected O
by O
immunoprecipitation O
/ O
Western O
blotting O
and O
confocal O
microscopy O
. O

Blocking O
studies O
using O
receptor O
for O
AGE B
siRNA O
and O
a O
specific O
inhibitor O
of O
Smad3 O
( O
SIS3 O
) O
were O
performed O
in O
MMECs O
and O
in O
STZ B
- O
induced O
diabetic O
nephropathy O
in O
Tie2 O
- O
Cre O
; O
Loxp O
- O
EGFP O
mice O
. O

RESULTS O
: O
Confocal O
microscopy O
and O
real O
- O
time O
PCR O
demonstrated O
that O
AGEs O
induced O
EndoMT O
in O
MMECs O
and O
in O
Tie2 O
- O
Cre O
; O
Loxp O
- O
EGFP O
mice O
. O

Immunoprecipitation O
/ O
Western O
blotting O
showed O
that O
Smad3 O
was O
activated O
by O
AGEs O
but O
was O
inhibited O
by O
SIS3 O
in O
MMECs O
and O
in O
STZ B
- O
induced O
diabetic O
nephropathy O
. O

Confocal O
microscopy O
and O
real O
- O
time O
PCR O
further O
demonstrated O
that O
SIS3 O
abrogated O
EndoMT O
, O
reduced O
renal O
fibrosis O
, O
and O
retarded O
progression O
of O
nephropathy O
. O

CONCLUSIONS O
: O
EndoMT O
is O
a O
novel O
pathway O
leading O
to O
early O
development O
of O
diabetic O
nephropathy O
. O

Blockade O
of O
EndoMT O
by O
SIS3 O
may O
provide O
a O
new O
strategy O
to O
retard O
the O
progression O
of O
diabetic O
nephropathy O
and O
other O
diabetes O
complications O
. O

Cytostatic O
and O
anti O
- O
angiogenic O
effects O
of O
temsirolimus B
in O
refractory O
mantle O
cell O
lymphoma O
. O

Mantle O
cell O
lymphoma O
( O
MCL O
) O
is O
a O
rare O
and O
aggressive O
type O
of O
B O
- O
cell O
non O
- O
Hodgkin O
' O
s O
lymphoma O
. O

Patients O
become O
progressively O
refractory O
to O
conventional O
chemotherapy O
, O
and O
their O
prognosis O
is O
poor O
. O

However O
, O
a O
38 O
% O
remission O
rate O
has O
been O
recently O
reported O
in O
refractory O
MCL O
treated O
with O
temsirolimus B
, O
a O
mTOR O
inhibitor O
. O
Here O
we O
had O
the O
opportunity O
to O
study O
a O
case O
of O
refractory O
MCL O
who O
had O
tumor O
regression O
two O
months O
after O
temsirolimus B
treatment O
, O
and O
a O
progression O
- O
free O
survival O
of O
10 O
months O
. O

In O
this O
case O
, O
lymph O
node O
biopsies O
were O
performed O
before O
and O
six O
months O
after O
temsirolimus B
therapy O
. O

Comparison O
of O
the O
two O
biopsies O
showed O
that O
temsirolimus B
inhibited O
tumor O
cell O
proliferation O
through O
cell O
cycle O
arrest O
, O
but O
did O
not O
induce O
any O
change O
in O
the O
number O
of O
apoptotic O
tumor O
cells O
. O

Apart O
from O
this O
cytostatic O
effect O
, O
temsirolimus B
had O
an O
antiangiogenic O
effect O
with O
decrease O
of O
tumor O
microvessel O
density O
and O
of O
VEGF O
expression O
. O

Moreover O
, O
numerous O
patchy O
, O
well O
- O
limited O
fibrotic O
areas O
, O
compatible O
with O
post O
- O
necrotic O
tissue O
repair O
, O
were O
found O
after O
6 O
- O
month O
temsirolimus B
therapy O
. O

Thus O
, O
temsirolimus B
reduced O
tumor O
burden O
through O
associated O
cytostatic O
and O
anti O
- O
angiogenic O
effects O
. O
This O
dual O
effect O
of O
temsirolimus B
on O
tumor O
tissue O
could O
contribute O
to O
its O
recently O
reported O
efficiency O
in O
refractory O
MCL O
resistant O
to O
conventional O
chemotherapy O
. O

Acute O
renal O
failure O
due O
to O
rifampicin B
. O

A O
23 O
- O
year O
- O
old O
male O
patient O
with O
bacteriologically O
proven O
pulmonary O
tuberculosis O
was O
treated O
with O
the O
various O
regimens O
of O
antituberculosis O
drugs O
for O
nearly O
15 O
months O
. O

Rifampicin B
was O
administered O
thrice O
as O
one O
of O
the O
3 O
- O
4 O
drug O
regimen O
and O
each O
time O
he O
developed O
untoward O
side O
effects O
like O
nausea O
, O
vomiting O
and O
fever O
with O
chills O
and O
rigors O
. O

The O
last O
such O
episode O
was O
of O
acute O
renal O
failure O
at O
which O
stage O
the O
patient O
was O
seen O
by O
the O
authors O
of O
this O
report O
. O

The O
patient O
, O
however O
, O
made O
a O
full O
recovery O
. O

Syncope O
caused O
by O
hyperkalemia O
during O
use O
of O
a O
combined O
therapy O
with O
the O
angiotensin B
- O
converting O
enzyme O
inhibitor O
and O
spironolactone B
. O

A O
76 O
year O
- O
old O
woman O
with O
a O
history O
of O
coronary O
artery O
bypass O
grafting O
and O
prior O
myocardial O
infarction O
was O
transferred O
to O
the O
emergency O
room O
with O
loss O
of O
consciousness O
due O
to O
marked O
bradycardia O
caused O
by O
hyperkalemia O
. O

The O
concentration O
of O
serum O
potassium B
was O
high O
, O
and O
normal O
sinus O
rhythm O
was O
restored O
after O
correction O
of O
the O
serum O
potassium B
level O
. O

The O
cause O
of O
hyperkalemia O
was O
considered O
to O
be O
several O
doses O
of O
spiranolactone B
, O
an O
aldosterone B
antagonist O
, O
in O
addition O
to O
the O
long O
- O
term O
intake O
of O
ramipril B
, O
an O
ACE B
inhibitor I
. O

This O
case O
is O
a O
good O
example O
of O
electrolyte O
imbalance O
causing O
acute O
life O
- O
threatening O
cardiac O
events O
. O

Clinicians O
should O
be O
alert O
to O
the O
possibility O
of O
hyperkalemia O
, O
especially O
in O
elderly O
patients O
using O
ACE O
/ O
ARB B
in O
combination O
with O
potassium B
sparing O
agents O
and O
who O
have O
mild O
renal O
disturbance O
. O

Diffuse O
skeletal O
pain O
after O
administration O
of O
alendronate B
. O

BACKGROUND O
: O
Osteoporosis O
is O
caused O
by O
bone O
resorption O
in O
excess O
of O
bone O
formation O
, O
and O
bisphosphonates B
, O
are O
used O
to O
inhibit O
bone O
resorption O
. O

Alendronate B
, O
a O
biphosphonate B
, O
is O
effective O
for O
both O
the O
treatment O
and O
prevention O
of O
osteoporosis O
in O
postmenopausal O
women O
. O

Side O
effects O
are O
relatively O
few O
and O
prominently O
gastrointestinal O
. O

Musculoskeletal O
pain O
may O
be O
an O
important O
side O
effect O
in O
these O
patients O
. O

We O
presented O
a O
patient O
admitted O
to O
our O
out O
- O
patient O
clinic O
with O
diffuse O
skeletal O
pain O
after O
three O
consecutive O
administration O
of O
alendronate B
. O

CONCLUSION O
: O
We O
conclude O
that O
patients O
with O
osteoporosis O
can O
report O
pain O
, O
and O
bisphosphonate B
- O
related O
pain O
should O
also O
be O
considered O
before O
ascribing O
this O
complaint O
to O
osteoporosis O
. O

Cerebrospinal O
fluid O
penetration O
of O
high O
- O
dose O
daptomycin B
in O
suspected O
Staphylococcus O
aureus O
meningitis O
. O

OBJECTIVE O
: O
To O
report O
a O
case O
of O
methicillin B
- O
sensitive O
Staphylococcus O
aureus O
( O
MSSA O
) O
bacteremia O
with O
suspected O
MSSA O
meningitis O
treated O
with O
high O
- O
dose O
daptomycin B
assessed O
with O
concurrent O
serum O
and O
cerebrospinal O
fluid O
( O
CSF O
) O
concentrations O
. O

CASE O
SUMMARY O
: O
A O
54 O
- O
year O
- O
old O
male O
presented O
to O
the O
emergency O
department O
with O
generalized O
weakness O
and O
presumed O
health O
- O
care O
- O
associated O
pneumonia O
shown O
on O
chest O
radiograph O
. O

Treatment O
was O
empirically O
initiated O
with O
vancomycin B
, O
levofloxacin B
, O
and O
piperacillin B
/ I
tazobactam I
. O

Blood O
cultures O
revealed O
S O
. O
aureus O
susceptible O
to O
oxacillin B
. O

Empiric O
antibiotic O
treatment O
was O
narrowed O
to O
nafcillin B
on O
day O
4 O
. O

On O
day O
8 O
, O
the O
patient O
developed O
acute O
renal O
failure O
( O
serum O
creatinine B
1 O
. O
9 O
mg O
/ O
dL O
, O
increased O
from O
1 O
. O
2 O
mg O
/ O
dL O
the O
previous O
day O
and O
0 O
. O
8 O
mg O
/ O
dL O
on O
admission O
) O
. O

The O
patient O
' O
s O
Glasgow O
Coma O
Score O
was O
3 O
, O
with O
normal O
findings O
shown O
on O
computed O
tomography O
scan O
of O
the O
head O
72 O
hours O
following O
an O
episode O
of O
cardiac O
arrest O
on O
day O
10 O
. O

The O
patient O
experienced O
relapsing O
MSSA O
bacteremia O
on O
day O
9 O
, O
increasing O
the O
suspicion O
for O
a O
central O
nervous O
system O
( O
CNS O
) O
infection O
. O

Nafcillin B
was O
discontinued O
and O
daptomycin B
9 O
mg O
/ O
kg O
daily O
was O
initiated O
for O
suspected O
meningitis O
and O
was O
continued O
until O
the O
patient O
' O
s O
death O
on O
day O
16 O
. O

Daptomycin B
serum O
and O
CSF O
trough O
concentrations O
were O
11 O
. O
21 O
ug O
/ O
mL O
and O
0 O
. O
52 O
ug O
/ O
mL O
, O
respectively O
, O
prior O
to O
the O
third O
dose O
. O

Lumbar O
puncture O
results O
were O
inconclusive O
and O
no O
further O
blood O
cultures O
were O
positive O
for O
MSSA O
. O

Creatine B
kinase O
levels O
were O
normal O
prior O
to O
daptomycin B
therapy O
and O
were O
not O
reassessed O
. O

DISCUSSION O
: O
Daptomycin B
was O
initiated O
in O
our O
patient O
secondary O
to O
possible O
nafcillin B
- O
induced O
acute O
interstitial O
nephritis O
and O
relapsing O
bacteremia O
. O

At O
a O
dose O
of O
9 O
mg O
/ O
kg O
, O
resultant O
penetration O
of O
5 O
% O
was O
higher O
than O
in O
previous O
reports O
, O
more O
consistent O
with O
inflamed O
meninges O
. O

CONCLUSIONS O
: O
High O
- O
dose O
daptomycin B
may O
be O
an O
alternative O
option O
for O
MSSA O
bacteremia O
with O
or O
without O
a O
CNS O
source O
in O
patients O
who O
have O
failed O
or O
cannot O
tolerate O
standard O
therapy O
. O

Further O
clinical O
evaluation O
in O
patients O
with O
confirmed O
meningitis O
is O
warranted O
. O

The O
role O
of O
nitric B
oxide I
in O
convulsions O
induced O
by O
lindane B
in O
rats O
. O

Lindane B
is O
an O
organochloride O
pesticide O
and O
scabicide O
. O

It O
evokes O
convulsions O
mainly O
trough O
the O
blockage O
of O
GABA B
( O
A O
) O
receptors O
. O

Nitric B
oxide I
( O
NO B
) O
, O
gaseous O
neurotransmitter O
, O
has O
contradictor O
role O
in O
epileptogenesis O
due O
to O
opposite O
effects O
of O
L B
- I
arginine I
, O
precursor O
of O
NO B
syntheses O
( O
NOS O
) O
, O
and O
L B
- I
NAME I
( O
NOS O
inhibitor O
) O
observed O
in O
different O
epilepsy O
models O
. O

The O
aim O
of O
the O
current O
study O
was O
to O
determine O
the O
effects O
of O
NO B
on O
the O
behavioral O
and O
EEG O
characteristics O
of O
lindane B
- O
induced O
epilepsy O
in O
male O
Wistar O
albino O
rats O
. O

The O
administration O
of O
L B
- I
arginine I
( O
600 O
, O
800 O
and O
1000 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
in O
dose O
- O
dependent O
manner O
significantly O
increased O
convulsion O
incidence O
and O
severity O
and O
shortened O
latency O
time O
to O
first O
convulsion O
elicited O
by O
lower O
lindane B
dose O
( O
4 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
. O

On O
the O
contrary O
, O
pretreatment O
with O
L B
- I
NAME I
( O
500 O
, O
700 O
and O
900 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
decreased O
convulsion O
incidence O
and O
severity O
and O
prolonged O
latency O
time O
to O
convulsion O
following O
injection O
with O
a O
convulsive O
dose O
of O
lindane B
( O
8 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
. O

EEG O
analyses O
showed O
increase O
of O
number O
and O
duration O
of O
ictal O
periods O
in O
EEG O
of O
rats O
receiving O
l B
- I
arginine I
prior O
to O
lindane B
and O
decrease O
of O
this O
number O
in O
rats O
pretreated O
with O
L B
- I
NAME I
. O

These O
results O
support O
the O
conclusion O
that O
NO B
plays O
a O
role O
of O
endogenous O
convulsant O
in O
rat O
model O
of O
lindane B
seizures O
. O

Severe O
polyneuropathy O
and O
motor O
loss O
after O
intrathecal O
thiotepa B
combination O
chemotherapy O
: O
description O
of O
two O
cases O
. O

Two O
cases O
of O
severe O
delayed O
neurologic O
toxicity O
related O
to O
the O
administration O
of O
intrathecal O
( O
IT O
) O
combination O
chemotherapy O
including O
thiotepa B
( O
TSPA B
) O
are O
presented O
. O

Both O
cases O
developed O
axonal O
neuropathy O
with O
motor O
predominance O
in O
the O
lower O
extremities O
1 O
and O
6 O
months O
after O
IT O
chemotherapy O
was O
administered O
. O

Neurologic O
toxicities O
have O
been O
described O
with O
IT O
- O
methotrexate B
, O
IT O
- O
cytosine B
arabinoside I
and O
IT O
- O
TSPA O
. O

To O
our O
knowledge O
, O
however O
, O
axonal O
neuropathy O
following O
administration O
of O
these O
three O
agents O
has O
not O
been O
previously O
described O
. O

In O
spite O
of O
the O
fact O
that O
TSPA B
is O
a O
useful O
IT O
agent O
, O
its O
combination O
with O
MTX B
, O
ara B
- I
C I
and O
radiotherapy O
could O
cause O
severe O
neurotoxicity O
. O

This O
unexpected O
complication O
indicates O
the O
need O
for O
further O
toxicology O
research O
on O
IT O
- O
TSPA B
. O

Effects O
of O
cromakalim B
and O
pinacidil B
on O
large O
epicardial O
and O
small O
coronary O
arteries O
in O
conscious O
dogs O
. O

The O
effects O
of O
i O
. O
v O
. O
bolus O
administration O
of O
cromakalim B
( O
1 O
- O
10 O
micrograms O
/ O
kg O
) O
and O
pinacidil B
( O
3 O
- O
100 O
micrograms O
/ O
kg O
) O
on O
large O
( O
circumflex O
artery O
) O
and O
small O
coronary O
arteries O
and O
on O
systemic O
hemodynamics O
were O
investigated O
in O
chronically O
instrumented O
conscious O
dogs O
and O
compared O
to O
those O
of O
nitroglycerin B
( O
0 O
. O
03 O
- O
10 O
micrograms O
/ O
kg O
) O
. O

Nitroglycerin B
, O
up O
to O
0 O
. O
3 O
micrograms O
/ O
kg O
, O
selectively O
increased O
circumflex O
artery O
diameter O
( O
CxAD O
) O
without O
simultaneously O
affecting O
any O
other O
cardiac O
or O
systemic O
hemodynamic O
parameter O
. O

In O
contrast O
, O
cromakalim B
and O
pinacidil B
at O
all O
doses O
and O
nitroglycerin B
at O
doses O
higher O
than O
0 O
. O
3 O
micrograms O
/ O
kg O
simultaneously O
and O
dose O
- O
dependently O
increased O
CxAD O
, O
coronary O
blood O
flow O
and O
heart O
rate O
and O
decreased O
coronary O
vascular O
resistance O
and O
aortic O
pressure O
. O

Cromakalim B
was O
approximately O
8 O
- O
to O
9 O
. O
5 O
- O
fold O
more O
potent O
than O
pinacidil B
in O
increasing O
CxAD B
. O

Vasodilation O
of O
large O
and O
small O
coronary O
vessels O
and O
hypotension O
induced O
by O
cromakalim B
and O
pinacidil B
were O
not O
affected O
by O
prior O
combined O
beta O
adrenergic O
and O
muscarinic O
receptors O
blockade O
but O
drug O
- O
induced O
tachycardia O
was O
abolished O
. O

When O
circumflex O
artery O
blood O
flow O
was O
maintained O
constant O
, O
the O
increases O
in O
CxAD O
induced O
by O
cromakalim B
( O
10 O
micrograms O
/ O
kg O
) O
, O
pinacidil B
( O
30 O
micrograms O
/ O
kg O
) O
and O
nitroglycerin B
( O
10 O
micrograms O
/ O
kg O
) O
were O
reduced O
by O
68 O
+ O
/ O
- O
7 O
, O
54 O
+ O
/ O
- O
9 O
and O
1 O
+ O
/ O
- O
1 O
% O
, O
respectively O
. O

Thus O
, O
whereas O
nitroglycerin B
preferentially O
and O
flow O
- O
independently O
dilates O
large O
coronary O
arteries O
, O
cromakalim B
and O
pinacidil B
dilate O
both O
large O
and O
small O
coronary O
arteries O
and O
this O
effect O
is O
not O
dependent O
upon O
the O
simultaneous O
beta O
adrenoceptors O
- O
mediated O
rise O
in O
myocardial O
metabolic O
demand O
. O

Finally O
, O
two O
mechanisms O
at O
least O
, O
direct O
vasodilation O
and O
flow O
dependency O
, O
are O
involved O
in O
the O
cromakalim B
- O
and O
pinacidil B
- O
induced O
increase O
in O
CxAD O
. O

Mefenamic B
acid I
- O
induced O
neutropenia O
and O
renal O
failure O
in O
elderly O
females O
with O
hypothyroidism O
. O

We O
report O
mefenamic B
acid I
- O
induced O
non O
- O
oliguric O
renal O
failure O
and O
severe O
neutropenia O
occurring O
simultaneously O
in O
two O
elderly O
females O
. O

The O
neutropenia O
was O
due O
to O
maturation O
arrest O
of O
the O
myeloid O
series O
in O
one O
patient O
. O

Both O
patients O
were O
also O
hypothyroid O
, O
but O
it O
is O
not O
clear O
whether O
this O
was O
a O
predisposing O
factor O
to O
the O
development O
of O
these O
adverse O
reactions O
. O

However O
, O
it O
would O
seem O
prudent O
not O
to O
use O
mefenamic B
acid I
in O
hypothyroid O
patients O
until O
the O
hypothyroidism O
has O
been O
corrected O
. O

Etiology O
of O
hypercalcemia O
in O
hemodialysis O
patients O
on O
calcium B
carbonate I
therapy O
. O

Fourteen O
of O
39 O
dialysis O
patients O
( O
36 O
% O
) O
became O
hypercalcemic O
after O
switching O
to O
calcium B
carbonate I
as O
their O
principal O
phosphate B
binder O
. O

In O
order O
to O
identify O
risk O
factors O
associated O
with O
the O
development O
of O
hypercalcemia O
, O
indirect O
parameters O
of O
intestinal O
calcium B
reabsorption O
and O
bone O
turnover O
rate O
in O
these O
14 O
patients O
were O
compared O
with O
results O
in O
14 O
eucalcemic O
patients O
matched O
for O
age O
, O
sex O
, O
length O
of O
time O
on O
dialysis O
, O
and O
etiology O
of O
renal O
disease O
. O

In O
addition O
to O
experiencing O
hypercalcemic O
episodes O
with O
peak O
calcium B
values O
of O
2 O
. O
7 O
to O
3 O
. O
8 O
mmol O
/ O
L O
( O
10 O
. O
7 O
to O
15 O
. O
0 O
mg O
/ O
dL O
) O
, O
patients O
in O
the O
hypercalcemic O
group O
exhibited O
a O
significant O
increase O
in O
the O
mean O
calcium B
concentration O
obtained O
during O
6 O
months O
before O
the O
switch O
, O
compared O
with O
the O
mean O
value O
obtained O
during O
the O
7 O
months O
of O
observation O
after O
the O
switch O
( O
2 O
. O
4 O
+ O
/ O
- O
0 O
. O
03 O
to O
2 O
. O
5 O
+ O
/ O
- O
0 O
. O
03 O
mmol O
/ O
L O
[ O
9 O
. O
7 O
+ O
/ O
- O
0 O
. O
2 O
to O
10 O
. O
2 O
+ O
/ O
- O
0 O
. O
1 O
mg O

/ O
dL O
] O
, O
P O
= O
0 O
. O
006 O
) O
. O

In O
contrast O
, O
eucalcemic O
patients O
exhibited O
no O
change O
in O
mean O
calcium B
values O
over O
the O
same O
time O
period O
( O
2 O
. O
3 O
+ O
/ O
- O
0 O
. O
05 O
to O
2 O
. O
3 O
+ O
/ O
- O
0 O
. O
05 O
mmol O
/ O
L O
[ O
9 O
. O
2 O
+ O
/ O
- O
0 O
. O
2 O
to O
9 O
. O
2 O
+ O
/ O
- O
0 O
. O
2 O
mg O
/ O
dL O
] O
) O
. O

CaCO3 B
dosage O
, O
calculated O
dietary O
calcium B
intake O
, O
and O
circulating O
levels O
of O
vitamin B
D I
metabolites O
were O
similar O
in O
both O
groups O
. O

Physical O
activity O
index O
and O
predialysis O
serum O
bicarbonate B
levels O
also O
were O
similar O
in O
both O
groups O
. O

However O
, O
there O
was O
a O
significant O
difference O
in O
parameters O
reflecting O
bone O
turnover O
rates O
between O
groups O
. O
( O
ABSTRACT O
TRUNCATED O
AT O
250 O
WORDS O
) O

Late O
- O
onset O
scleroderma O
renal O
crisis O
induced O
by O
tacrolimus B
and O
prednisolone B
: O
a O
case O
report O
. O

Scleroderma O
renal O
crisis O
( O
SRC O
) O
is O
a O
rare O
complication O
of O
systemic O
sclerosis O
( O
SSc O
) O
but O
can O
be O
severe O
enough O
to O
require O
temporary O
or O
permanent O
renal O
replacement O
therapy O
. O

Moderate O
to O
high O
dose O
corticosteroid B
use O
is O
recognized O
as O
a O
major O
risk O
factor O
for O
SRC O
. O

Furthermore O
, O
there O
have O
been O
reports O
of O
thrombotic O
microangiopathy O
precipitated O
by O
cyclosporine B
in O
patients O
with O
SSc O
. O

In O
this O
article O
, O
we O
report O
a O
patient O
with O
SRC O
induced O
by O
tacrolimus B
and O
corticosteroids B
. O

The O
aim O
of O
this O
work O
is O
to O
call O
attention O
to O
the O
risk O
of O
tacrolimus B
use O
in O
patients O
with O
SSc O
. O

Methyldopa B
- O
induced O
hemolytic O
anemia O
in O
a O
15 O
year O
old O
presenting O
as O
near O
- O
syncope O
. O

Methyldopa B
is O
an O
antihypertensive O
medication O
which O
is O
available O
generically O
and O
under O
the O
trade O
name O
Aldomet B
that O
is O
widely O
prescribed O
in O
the O
adult O
population O
and O
infrequently O
used O
in O
children O
. O

Methyldopa B
causes O
an O
autoimmune O
hemolytic O
anemia O
in O
a O
small O
percentage O
of O
patients O
who O
take O
the O
drug O
. O

We O
report O
a O
case O
of O
methyldopa B
- O
induced O
hemolytic O
anemia O
in O
a O
15 O
- O
year O
- O
old O
boy O
who O
presented O
to O
the O
emergency O
department O
with O
near O
- O
syncope O
. O

The O
boy O
had O
been O
treated O
with O
intravenous O
methyldopa B
during O
a O
trauma O
admission O
seven O
weeks O
prior O
to O
presentation O
. O

Evaluation O
revealed O
a O
hemoglobin O
of O
three O
grams O
, O
3 O
+ O
Coombs O
' O
test O
with O
polyspecific O
anti O
- O
human O
globulin O
and O
monospecific O
IgG O
reagents O
, O
and O
a O
warm O
reacting O
autoantibody O
. O

Transfusion O
and O
corticosteroid O
therapy O
resulted O
in O
a O
complete O
recovery O
of O
the O
patient O
. O

Emergency O
physicians O
treating O
children O
must O
be O
aware O
of O
this O
syndrome O
in O
order O
to O
diagnose O
and O
treat O
it O
correctly O
. O

A O
brief O
review O
of O
autoimmune O
and O
drug O
- O
induced O
hemolytic O
anemias O
is O
provided O
. O

The O
risk O
and O
associated O
factors O
of O
methamphetamine B
psychosis O
in O
methamphetamine B
- O
dependent O
patients O
in O
Malaysia O
. O

OBJECTIVE O
: O
The O
objective O
of O
this O
study O
was O
to O
determine O
the O
risk O
of O
lifetime O
and O
current O
methamphetamine B
- O
induced O
psychosis O
in O
patients O
with O
methamphetamine B
dependence O
. O

The O
association O
between O
psychiatric O
co O
- O
morbidity O
and O
methamphetamine B
- O
induced O
psychosis O
was O
also O
studied O
. O

METHODS O
: O
This O
was O
a O
cross O
- O
sectional O
study O
conducted O
concurrently O
at O
a O
teaching O
hospital O
and O
a O
drug O
rehabilitation O
center O
in O
Malaysia O
. O

Patients O
with O
the O
diagnosis O
of O
methamphetamine B
based O
on O
DSM O
- O
IV O
were O
interviewed O
using O
the O
Mini O
International O
Neuropsychiatric O
Interview O
( O
M O
. O
I O
. O
N O
. O
I O
. O
) O
for O
methamphetamine B
- O
induced O
psychosis O
and O
other O
Axis O
I O
psychiatric O
disorders O
. O

The O
information O
on O
sociodemographic O
background O
and O
drug O
use O
history O
was O
obtained O
from O
interview O
or O
medical O
records O
. O

RESULTS O
: O
Of O
292 O
subjects O
, O
47 O
. O
9 O
% O
of O
the O
subjects O
had O
a O
past O
history O
of O
psychotic O
symptoms O
and O
13 O
. O
0 O
% O
of O
the O
patients O
were O
having O
current O
psychotic O
symptoms O
. O

Co O
- O
morbid O
major O
depressive O
disorder O
( O
OR O
= O
7 O
. O
18 O
, O
95 O
CI O
= O
2 O
. O
612 O
- O
19 O
. O
708 O
) O
, O
bipolar O
disorder O
( O
OR O
= O
13 O
. O
807 O
, O
95 O
CI O
= O
5 O
. O
194 O
- O
36 O
. O
706 O
) O
, O
antisocial O
personality O
disorder O
( O
OR O
= O
12 O
. O
619 O
, O
95 O
CI O
= O
6 O
. O
702 O
- O
23 O
. O
759 O
) O
and O
heavy O
methamphetamine B
uses O
were O
significantly O
associated O
with O
lifetime O
methamphetamine B
- O
induced O
psychosis O
after O
adjusted O
for O
other O
factors O
. O

Major O
depressive O
disorder O
( O
OR O
= O
2 O
. O
870 O
, O
CI O
= O
1 O
. O
154 O
- O
7 O
. O
142 O
) O
and O
antisocial O
personality O
disorder O
( O
OR O
= O
3 O
. O
299 O
, O
95 O
CI O
= O
1 O
. O
375 O
- O
7 O
. O
914 O
) O
were O
the O
only O
factors O
associated O
with O
current O
psychosis O
. O

CONCLUSION O
: O
There O
was O
a O
high O
risk O
of O
psychosis O
in O
patients O
with O
methamphetamine B
dependence O
. O

It O
was O
associated O
with O
co O
- O
morbid O
affective O
disorder O
, O
antisocial O
personality O
, O
and O
heavy O
methamphetamine B
use O
. O

It O
is O
recommended O
that O
all O
cases O
of O
methamphetamine B
dependence O
should O
be O
screened O
for O
psychotic O
symptoms O
. O

Cerebellar O
sensory O
processing O
alterations O
impact O
motor O
cortical O
plasticity O
in O
Parkinson O
' O
s O
disease O
: O
clues O
from O
dyskinetic O
patients O
. O

The O
plasticity O
of O
primary O
motor O
cortex O
( O
M1 O
) O
in O
patients O
with O
Parkinson O
' O
s O
disease O
( O
PD O
) O
and O
levodopa B
- O
induced O
dyskinesias O
( O
LIDs O
) O
is O
severely O
impaired O
. O

We O
recently O
reported O
in O
young O
healthy O
subjects O
that O
inhibitory O
cerebellar O
stimulation O
enhanced O
the O
sensorimotor O
plasticity O
of O
M1 O
that O
was O
induced O
by O
paired O
associative O
stimulation O
( O
PAS O
) O
. O

This O
study O
demonstrates O
that O
the O
deficient O
sensorimotor O
M1 O
plasticity O
in O
16 O
patients O
with O
LIDs O
could O
be O
reinstated O
by O
a O
single O
session O
of O
real O
inhibitory O
cerebellar O
stimulation O
but O
not O
sham O
stimulation O
. O

This O
was O
evident O
only O
when O
a O
sensory O
component O
was O
involved O
in O
the O
induction O
of O
plasticity O
, O
indicating O
that O
cerebellar O
sensory O
processing O
function O
is O
involved O
in O
the O
resurgence O
of O
M1 O
plasticity O
. O

The O
benefit O
of O
inhibitory O
cerebellar O
stimulation O
on O
LIDs O
is O
known O
. O

To O
explore O
whether O
this O
benefit O
is O
linked O
to O
the O
restoration O
of O
sensorimotor O
plasticity O
of O
M1 O
, O
we O
conducted O
an O
additional O
study O
looking O
at O
changes O
in O
LIDs O
and O
PAS O
- O
induced O
plasticity O
after O
10 O
sessions O
of O
either O
bilateral O
, O
real O
inhibitory O
cerebellar O
stimulation O
or O
sham O
stimulation O
. O

Only O
real O
and O
not O
sham O
stimulation O
had O
an O
antidyskinetic O
effect O
and O
it O
was O
paralleled O
by O
a O
resurgence O
in O
the O
sensorimotor O
plasticity O
of O
M1 O
. O

These O
results O
suggest O
that O
alterations O
in O
cerebellar O
sensory O
processing O
function O
, O
occurring O
secondary O
to O
abnormal O
basal O
ganglia O
signals O
reaching O
it O
, O
may O
be O
an O
important O
element O
contributing O
to O
the O
maladaptive O
sensorimotor O
plasticity O
of O
M1 O
and O
the O
emergence O
of O
abnormal O
involuntary O
movements O
. O

The O
long O
- O
term O
safety O
of O
danazol B
in O
women O
with O
hereditary O
angioedema O
. O

Although O
the O
short O
- O
term O
safety O
( O
less O
than O
or O
equal O
to O
6 O
months O
) O
of O
danazol B
has O
been O
established O
in O
a O
variety O
of O
settings O
, O
no O
information O
exists O
as O
to O
its O
long O
- O
term O
safety O
. O

We O
therefore O
investigated O
the O
long O
- O
term O
safety O
of O
danazol B
by O
performing O
a O
retrospective O
chart O
review O
of O
60 O
female O
patients O
with O
hereditary O
angioedema O
treated O
with O
danazol B
for O
a O
continuous O
period O
of O
6 O
months O
or O
longer O
. O

The O
mean O
age O
of O
the O
patients O
was O
35 O
. O
2 O
years O
and O
the O
mean O
duration O
of O
therapy O
was O
59 O
. O
7 O
months O
. O

Virtually O
all O
patients O
experienced O
one O
or O
more O
adverse O
reactions O
. O

Menstrual O
abnormalities O
( O
79 O
% O
) O
, O
weight O
gain O
( O
60 O
% O
) O
, O
muscle O
cramps O
/ O
myalgias O
( O
40 O
% O
) O
, O
and O
transaminase O
elevations O
( O
40 O
% O
) O
were O
the O
most O
common O
adverse O
reactions O
. O

The O
drug O
was O
discontinued O
due O
to O
adverse O
reactions O
in O
8 O
patients O
. O

No O
patient O
has O
died O
or O
suffered O
any O
apparent O
long O
- O
term O
sequelae O
that O
were O
directly O
attributable O
to O
the O
drug O
. O

We O
conclude O
that O
, O
despite O
a O
relatively O
high O
incidence O
of O
adverse O
reactions O
, O
danazol B
has O
proven O
to O
be O
remarkably O
safe O
over O
the O
long O
- O
term O
in O
this O
group O
of O
patients O
. O

The O
function O
of O
P2X3 O
receptor O
and O
NK1 O
receptor O
antagonists O
on O
cyclophosphamide B
- O
induced O
cystitis O
in O
rats O
. O

PURPOSE O
: O
The O
purpose O
of O
the O
study O
is O
to O
explore O
the O
function O
of O
P2X3 O
and O
NK1 O
receptors O
antagonists O
on O
cyclophosphamide B
( O
CYP B
) O
- O
induced O
cystitis O
in O
rats O
. O

METHODS O
: O
Sixty O
female O
Sprague O
- O
Dawley O
( O
SD O
) O
rats O
were O
randomly O
divided O
into O
three O
groups O
. O

The O
rats O
in O
the O
control O
group O
were O
intraperitoneally O
( O
i O
. O
p O
. O
) O
injected O
with O
0 O
. O
9 O
% O
saline O
( O
4 O
ml O
/ O
kg O
) O
; O
the O
rats O
in O
the O
model O
group O
were O
i O
. O
p O
. O
injected O
with O
CYP B
( O
150 O
mg O
/ O
kg O
) O
; O
and O
the O
rats O
in O
the O
intervention O
group O
were O
i O
. O
p O
. O
injected O
with O
CYP B
with O
subsequently O
perfusion O
of O
bladder O
with O
P2X3 O
and O
NK1 O
receptors O
' O
antagonists O
, O
Suramin B
and O
GR B
82334 I
. O

Spontaneous O
pain O
behaviors O
following O
the O
administration O
of O
CYP B
were O
observed O
. O

Urodynamic O
parameters O
, O
bladder O
pressure O
- O
volume O
curve O
, O
maximum O
voiding O
pressure O
( O
MVP O
) O
, O
and O
maximum O
cystometric O
capacity O
( O
MCC O
) O
, O
were O
recorded O
. O

Pathological O
changes O
in O
bladder O
tissue O
were O
observed O
. O

Immunofluorescence O
was O
used O
to O
detect O
the O
expression O
of O
P2X3 O
and O
NK1 O
receptors O
in O
bladder O
. O

RESULTS O
: O
Cyclophosphamide B
treatment O
increased O
the O
spontaneous O
pain O
behaviors O
scores O
. O

The O
incidence O
of O
bladder O
instability O
during O
urine O
storage O
period O
of O
model O
group O
was O
significantly O
higher O
than O
intervention O
group O
( O
X O
( O
2 O
) O
= O
7 O
. O
619 O
, O
P O
= O
0 O
. O
007 O
) O
and O
control O
group O
( O
X O
( O
2 O
) O
= O
13 O
. O
755 O
, O
P O
= O
0 O
. O
000 O
) O
. O

MCC O
in O
the O
model O
group O
was O
lower O
than O
the O
control O
and O
intervention O
groups O
( O
P O
< O
0 O
. O
01 O
) O
. O

Histological O
changes O
evident O
in O
model O
and O
intervention O
groups O
rats O
' O
bladder O
included O
edema O
, O
vasodilation O
, O
and O
infiltration O
of O
inflammatory O
cells O
. O

In O
model O
group O
, O
the O
expression O
of O
P2X3 O
receptor O
increased O
in O
urothelium O
and O
suburothelium O
, O
and O
NK1 O
receptor O
increased O
in O
suburothelium O
, O
while O
the O
expression O
of O
them O
in O
intervention O
group O
was O
lower O
. O

CONCLUSIONS O
: O
In O
CYP B
- O
induced O
cystitis O
, O
the O
expression O
of O
P2X3 O
and O
NK1 O
receptors O
increased O
in O
urothelium O
and O
/ O
or O
suburothelium O
. O

Perfusion O
of O
bladder O
with O
P2X3 O
and O
NK1 O
receptors O
antagonists O
ameliorated O
the O
bladder O
function O
. O

Patient O
tolerance O
study O
of O
topical O
chlorhexidine B
diphosphanilate I
: O
a O
new O
topical O
agent O
for O
burns O
. O

Effective O
topical O
antimicrobial O
agents O
decrease O
infection O
and O
mortality O
in O
burn O
patients O
. O

Chlorhexidine B
phosphanilate I
( O
CHP B
) O
, O
a O
new O
broad O
- O
spectrum O
antimicrobial O
agent O
, O
has O
been O
evaluated O
as O
a O
topical O
burn O
wound O
dressing O
in O
cream O
form O
, O
but O
preliminary O
clinical O
trials O
reported O
that O
it O
was O
painful O
upon O
application O
. O

This O
study O
compared O
various O
concentrations O
of O
CHP B
to O
determine O
if O
a O
tolerable O
concentration O
could O
be O
identified O
with O
retention O
of O
antimicrobial O
efficacy O
. O

Twenty O
- O
nine O
burn O
patients O
, O
each O
with O
two O
similar O
burns O
which O
could O
be O
separately O
treated O
, O
were O
given O
pairs O
of O
treatments O
at O
successive O
12 O
- O
h O
intervals O
over O
a O
3 O
- O
day O
period O
. O

One O
burn O
site O
was O
treated O
with O
each O
of O
four O
different O
CHP B
concentrations O
, O
from O
0 O
. O
25 O
per O
cent O
to O
2 O
per O
cent O
, O
their O
vehicle O
, O
and O
1 O
per O
cent O
silver B
sulphadiazine I
( O
AgSD B
) O
cream O
, O
an O
antimicrobial O
agent O
frequently O
used O
for O
topical O
treatment O
of O
burn O
wounds O
. O

The O
other O
site O
was O
always O
treated O
with O
AgSD B
cream O
. O

There O
was O
a O
direct O
relationship O
between O
CHP B
concentration O
and O
patients O
' O
ratings O
of O
pain O
on O
an O
analogue O
scale O
. O

The O
0 O
. O
25 O
per O
cent O
CHP O
cream O
was O
closest O
to O
AgSD O
in O
pain O
tolerance O
; O
however O
, O
none O
of O
the O
treatments O
differed O
statistically O
from O
AgSD O
or O
from O
each O
other O
. O

In O
addition O
, O
ease O
of O
application O
of O
CHP B
creams O
was O
less O
satisfactory O
than O
that O
of O
AgSD O
. O

It O
was O
concluded O
that O
formulations O
at O
or O
below O
0 O
. O
5 O
per O
cent O
CHP B
may O
prove O
acceptable O
for O
wound O
care O
, O
but O
the O
vehicle O
system O
needs O
pharmaceutical O
improvement O
to O
render O
it O
more O
tolerable O
and O
easier O
to O
use O
. O

Acute O
hepatitis O
associated O
with O
clopidogrel B
: O
a O
case O
report O
and O
review O
of O
the O
literature O
. O

Drug O
- O
induced O
hepatotoxicity O
is O
a O
common O
cause O
of O
acute O
hepatitis O
, O
and O
the O
recognition O
of O
the O
responsible O
drug O
may O
be O
difficult O
. O

We O
describe O
a O
case O
of O
clopidogrel B
- O
related O
acute O
hepatitis O
. O

The O
diagnosis O
is O
strongly O
suggested O
by O
an O
accurate O
medical O
history O
and O
liver O
biopsy O
. O

Reports O
about O
cases O
of O
hepatotoxicity O
due O
to O
clopidogrel B
are O
increasing O
in O
the O
last O
few O
years O
, O
after O
the O
increased O
use O
of O
this O
drug O
. O

In O
conclusion O
, O
we O
believe O
that O
physicians O
should O
carefully O
consider O
the O
risk O
of O
drug O
- O
induced O
hepatic O
injury O
when O
clopidogrel B
is O
prescribed O
. O

Bortezomib B
and O
dexamethasone B
as O
salvage O
therapy O
in O
patients O
with O
relapsed O
/ O
refractory O
multiple O
myeloma O
: O
analysis O
of O
long O
- O
term O
clinical O
outcomes O
. O

Bortezomib B
( O
bort B
) O
- O
dexamethasone B
( O
dex B
) O
is O
an O
effective O
therapy O
for O
relapsed O
/ O
refractory O
( O
R O
/ O
R O
) O
multiple O
myeloma O
( O
MM O
) O
. O

This O
retrospective O
study O
investigated O
the O
combination O
of O
bort B
( O
1 O
. O
3 O
mg O
/ O
m O
( O
2 O
) O
on O
days O
1 O
, O
4 O
, O
8 O
, O
and O
11 O
every O
3 O
weeks O
) O
and O
dex B
( O
20 O
mg O
on O
the O
day O
of O
and O
the O
day O
after O
bort B
) O
as O
salvage O
treatment O
in O
85 O
patients O
with O
R O
/ O
R O
MM O
after O
prior O
autologous O
stem O
cell O
transplantation O
or O
conventional O
chemotherapy O
. O

The O
median O
number O
of O
prior O
lines O
of O
therapy O
was O
2 O
. O

Eighty O
- O
seven O
percent O
of O
the O
patients O
had O
received O
immunomodulatory O
drugs O
included O
in O
some O
line O
of O
therapy O
before O
bort B
- O
dex B
. O

The O
median O
number O
of O
bort O
- O
dex B
cycles O
was O
6 O
, O
up O
to O
a O
maximum O
of O
12 O
cycles O
. O

On O
an O
intention O
- O
to O
- O
treat O
basis O
, O
55 O
% O
of O
the O
patients O
achieved O
at O
least O
partial O
response O
, O
including O
19 O
% O
CR O
and O
35 O
% O
achieved O
at O
least O
very O
good O
partial O
response O
. O

Median O
durations O
of O
response O
, O
time O
to O
next O
therapy O
and O
treatment O
- O
free O
interval O
were O
8 O
, O
11 O
. O
2 O
, O
and O
5 O
. O
1 O
months O
, O
respectively O
. O

The O
most O
relevant O
adverse O
event O
was O
peripheral O
neuropathy O
, O
which O
occurred O
in O
78 O
% O
of O
the O
patients O
( O
grade O
II O
, O
38 O
% O
; O
grade O
III O
, O
21 O
% O
) O
and O
led O
to O
treatment O
discontinuation O
in O
6 O
% O
. O

With O
a O
median O
follow O
up O
of O
22 O
months O
, O
median O
time O
to O
progression O
, O
progression O
- O
free O
survival O
( O
PFS O
) O
and O
overall O
survival O
( O
OS O
) O
were O
8 O
. O
9 O
, O
8 O
. O
7 O
, O
and O
22 O
months O
, O
respectively O
. O

Prolonged O
PFS O
and O
OS O
were O
observed O
in O
patients O
achieving O
CR O
and O
receiving O
bort B
- O
dex B
a O
single O
line O
of O
prior O
therapy O
. O

Bort B
- O
dex B
was O
an O
effective O
salvage O
treatment O
for O
MM O
patients O
, O
particularly O
for O
those O
in O
first O
relapse O
. O

Pubertal O
exposure O
to O
Bisphenol B
A I
increases O
anxiety O
- O
like O
behavior O
and O
decreases O
acetylcholinesterase O
activity O
of O
hippocampus O
in O
adult O
male O
mice O
. O

The O
negative O
effects O
of O
Bisphenol B
A I
( O
BPA B
) O
on O
neurodevelopment O
and O
behaviors O
have O
been O
well O
established O
. O

Acetylcholinesterase O
( O
AChE O
) O
is O
a O
regulatory O
enzyme O
which O
is O
involved O
in O
anxiety O
- O
like O
behavior O
. O

This O
study O
investigated O
behavioral O
phenotypes O
and O
AChE O
activity O
in O
male O
mice O
following O
BPA B
exposure O
during O
puberty O
. O

On O
postnatal O
day O
( O
PND O
) O
35 O
, O
male O
mice O
were O
exposed O
to O
50mg O
BPA B
/ O
kg O
diet O
per O
day O
for O
a O
period O
of O
35 O
days O
. O

On O
PND71 O
, O
a O
behavioral O
assay O
was O
performed O
using O
the O
elevated O
plus O
maze O
( O
EPM O
) O
and O
the O
light O
/ O
dark O
test O
. O

In O
addition O
, O
AChE O
activity O
was O
measured O
in O
the O
prefrontal O
cortex O
, O
hypothalamus O
, O
cerebellum O
and O
hippocampus O
. O

Results O
from O
our O
behavioral O
phenotyping O
indicated O
that O
anxiety O
- O
like O
behavior O
was O
increased O
in O
mice O
exposed O
to O
BPA B
. O

AChE O
activity O
was O
significantly O
decreased O
in O
the O
hippocampus O
of O
mice O
with O
BPA B
compared O
to O
control O
mice O
, O
whereas O
no O
difference O
was O
found O
in O
the O
prefrontal O
cortex O
, O
hypothalamus O
and O
cerebellum O
. O

Our O
findings O
showed O
that O
pubertal O
BPA B
exposure O
increased O
anxiety O
- O
like O
behavior O
, O
which O
may O
be O
associated O
with O
decreased O
AChE O
activity O
of O
the O
hippocampus O
in O
adult O
male O
mice O
. O

Further O
studies O
are O
necessary O
to O
investigate O
the O
cholinergic O
signaling O
of O
the O
hippocampus O
in O
PBE B
induced O
anxiety O
- O
like O
behaviors O
. O

Biochemical O
effects O
of O
Solidago O
virgaurea I
extract O
on O
experimental O
cardiotoxicity O
. O

Cardiovascular O
diseases O
( O
CVDs O
) O
are O
the O
major O
health O
problem O
of O
advanced O
as O
well O
as O
developing O
countries O
of O
the O
world O
. O

The O
aim O
of O
the O
present O
study O
was O
to O
investigate O
the O
protective O
effect O
of O
the O
Solidago O
virgaurea O
extract O
on O
isoproterenol B
- O
induced O
cardiotoxicity O
in O
rats O
. O

The O
subcutaneous O
injection O
of O
isoproterenol B
( O
30 O
mg O
/ O
kg O
) O
into O
rats O
twice O
at O
an O
interval O
of O
24 O
h O
, O
for O
two O
consecutive O
days O
, O
led O
to O
a O
significant O
increase O
in O
serum O
lactate B
dehydrogenase O
, O
creatine B
phosphokinase O
, O
alanine B
transaminase O
, O
aspartate B
transaminase O
, O
and O
angiotensin B
- O
converting O
enzyme O
activities O
, O
total O
cholesterol B
, O
triglycerides B
, O
free O
serum O
fatty B
acid I
, O
cardiac O
tissue O
malondialdehyde B
( O
MDA B
) O
, O
and O
nitric B
oxide I
levels O
and O
a O
significant O
decrease O
in O
levels O
of O

glutathione B
and O
superoxide B
dismutase O
in O
cardiac O
tissue O
as O
compared O
to O
the O
normal O
control O
group O
( O
P O
< O
0 O
. O
05 O
) O
. O

Pretreatment O
with O
S B
. I
virgaurea I
extract I
for O
5 O
weeks O
at O
a O
dose O
of O
250 O
mg O
/ O
kg O
followed O
by O
isoproterenol B
injection O
significantly O
prevented O
the O
observed O
alterations O
. O

Captopril B
( O
50 O
mg O
/ O
kg O
/ O
day O
, O
given O
orally O
) O
, O
an O
inhibitor O
of O
angiotensin B
- O
converting O
enzyme O
used O
as O
a O
standard O
cardioprotective O
drug O
, O
was O
used O
as O
a O
positive O
control O
in O
this O
study O
. O

The O
data O
of O
the O
present O
study O
suggest O
that O
S B
. I
virgaurea I
extract I
exerts O
its O
protective O
effect O
by O
decreasing O
MDA B
level O
and O
increasing O
the O
antioxidant O
status O
in O
isoproterenol B
- O
treated O
rats O
. O

The O
study O
emphasizes O
the O
beneficial O
action O
of O
S B
. I
virgaurea I
extract I
as O
a O
cardioprotective O
agent O
. O

" O
Real O
- O
world O
" O
data O
on O
the O
efficacy O
and O
safety O
of O
lenalidomide B
and O
dexamethasone B
in O
patients O
with O
relapsed O
/ O
refractory O
multiple O
myeloma O
who O
were O
treated O
according O
to O
the O
standard O
clinical O
practice O
: O
a O
study O
of O
the O
Greek O
Myeloma O
Study O
Group O
. O

Lenalidomide B
and O
dexamethasone B
( O
RD O
) O
is O
a O
standard O
of O
care O
for O
relapsed O
/ O
refractory O
multiple O
myeloma O
( O
RRMM O
) O
, O
but O
there O
is O
limited O
published O
data O
on O
its O
efficacy O
and O
safety O
in O
the O
" O
real O
world O
" O
( O
RW O
) O
, O
according O
to O
the O
International O
Society O
of O
Pharmacoeconomics O
and O
Outcomes O
Research O
definition O
. O

We O
studied O
212 O
RRMM O
patients O
who O
received O
RD O
in O
RW O
. O

Objective O
response O
( O
> O
PR O
( O
partial O
response O
) O
) O
rate O
was O
77 O
. O
4 O
% O
( O
complete O
response O
( O
CR O
) O
, O
20 O
. O
2 O
% O
) O
. O

Median O
time O
to O
first O
and O
best O
response O
was O
2 O
and O
5 O
months O
, O
respectively O
. O

Median O
time O
to O
CR O
when O
RD O
was O
given O
as O
2nd O
or O
> O
2 O
( O
nd O
) O
- O
line O
treatment O
at O
4 O
and O
11 O
months O
, O
respectively O
. O

Quality O
of O
response O
was O
independent O
of O
previous O
lines O
of O
therapies O
or O
previous O
exposure O
to O
thalidomide B
or O
bortezomib B
. O

Median O
duration O
of O
response O
was O
34 O
. O
4 O
months O
, O
and O
it O
was O
higher O
in O
patients O
who O
received O
RD O
until O
progression O
( O
not O
reached O
versus O
19 O
months O
, O
p O
< O
0 O
. O
001 O
) O
. O

Improvement O
of O
humoral O
immunity O
occurred O
in O
60 O
% O
of O
responders O
( O
p O
< O
0 O
. O
001 O
) O
and O
in O
the O
majority O
of O
patients O
who O
achieved O
stable O
disease O
. O

Adverse O
events O
were O
reported O
in O
68 O
. O
9 O
% O
of O
patients O
( O
myelosuppression O
in O
49 O
. O
4 O
% O
) O
and O
12 O
. O
7 O
% O
of O
patients O
needed O
hospitalization O
. O

Peripheral O
neuropathy O
was O
observed O
only O
in O
2 O
. O
5 O
% O
of O
patients O
and O
deep O
vein O
thrombosis O
in O
5 O
. O
7 O
% O
. O

Dose O
reductions O
were O
needed O
in O
31 O
% O
of O
patients O
and O
permanent O
discontinuation O
in O
38 O
. O
9 O
% O
. O

Median O
time O
to O
treatment O
discontinuation O
was O
16 O
. O
8 O
months O
. O

Performance O
status O
( O
PS O
) O
and O
initial O
lenalidomide B
dose O
predicted O
for O
treatment O
discontinuation O
. O

Extra O
- O
medullary O
relapses O
occurred O
in O
3 O
. O
8 O
% O
of O
patients O
. O

Our O
study O
confirms O
that O
RD O
is O
effective O
and O
safe O
in O
RRMM O
in O
the O
RW O
; O
it O
produces O
durable O
responses O
especially O
in O
patients O
who O
continue O
on O
treatment O
till O
progression O
and O
improves O
humoral O
immunity O
even O
in O
patients O
with O
stable O
disease O
. O

The O
cytogenetic O
action O
of O
ifosfamide B
, O
mesna B
, O
and O
their O
combination O
on O
peripheral O
rabbit O
lymphocytes O
: O
an O
in O
vivo O
/ O
in O
vitro O
cytogenetic O
study O
. O

Ifosfamide B
( O
IFO B
) O
is O
an O
alkylating O
nitrogen B
mustard I
, O
administrated O
as O
an O
antineoplasmic O
agent O
. O

It O
is O
characterized O
by O
its O
intense O
urotoxic O
action O
, O
leading O
to O
hemorrhagic O
cystitis O
. O

This O
side O
effect O
of O
IFO B
raises O
the O
requirement O
for O
the O
co O
- O
administration O
with O
sodium B
2 I
- I
sulfanylethanesulfonate I
( O
Mesna B
) O
aiming O
to O
avoid O
or O
minimize O
this O
effect O
. O

IFO B
and O
Mesna B
were O
administrated O
separately O
on O
rabbit O
' O
s O
lymphocytes O
in O
vivo O
, O
which O
were O
later O
developed O
in O
vitro O
. O

Cytogenetic O
markers O
for O
sister O
chromatid O
exchanges O
( O
SCEs O
) O
, O
proliferation O
rate O
index O
( O
PRI O
) O
and O
Mitotic O
Index O
were O
recorded O
. O

Mesna B
' O
s O
action O
, O
in O
conjunction O
with O
IFO B
reduces O
the O
frequency O
of O
SCEs O
, O
in O
comparison O
with O
the O
SCEs O
recordings O
obtained O
when O
IFO B
is O
administered O
alone O
. O

In O
addition O
to O
this O
, O
when O
high O
concentrations O
of O
Mesna B
were O
administered O
alone O
significant O
reductions O
of O
the O
PRI O
were O
noted O
, O
than O
with O
IFO B
acting O
at O
the O
same O
concentration O
on O
the O
lymphocytes O
. O

Mesna B
significantly O
reduces O
IFO B
' O
s O
genotoxicity O
, O
while O
when O
administered O
in O
high O
concentrations O
it O
acts O
in O
an O
inhibitory O
fashion O
on O
the O
cytostatic O
action O
of O
the O
drug O
. O

Risk O
factors O
and O
predictors O
of O
levodopa B
- O
induced O
dyskinesia O
among O
multiethnic O
Malaysians O
with O
Parkinson O
' O
s O
disease O
. O

Chronic O
pulsatile O
levodopa B
therapy O
for O
Parkinson O
' O
s O
disease O
( O
PD O
) O
leads O
to O
the O
development O
of O
motor O
fluctuations O
and O
dyskinesia O
. O

We O
studied O
the O
prevalence O
and O
predictors O
of O
levodopa B
- O
induced O
dyskinesia O
among O
multiethnic O
Malaysian O
patients O
with O
PD O
. O

METHODS O
: O
This O
is O
a O
cross O
- O
sectional O
study O
involving O
95 O
patients O
with O
PD O
on O
uninterrupted O
levodopa B
therapy O
for O
at O
least O
6 O
months O
. O

The O
instrument O
used O
was O
the O
UPDRS O
questionnaires O
. O

The O
predictors O
of O
dyskinesia O
were O
determined O
using O
multivariate O
logistic O
regression O
analysis O
. O

RESULTS O
: O
The O
mean O
age O
was O
65 O
. O
6 O
+ O
8 O
. O
5 O
years O
. O

The O
mean O
onset O
age O
was O
58 O
. O
5 O
+ O
9 O
. O
8 O
years O
. O

The O
median O
disease O
duration O
was O
6 O
( O
7 O
) O
years O
. O

Dyskinesia O
was O
present O
in O
44 O
% O
( O
n O
= O
42 O
) O
with O
median O
levodopa B
therapy O
of O
3 O
years O
. O

There O
were O
64 O
. O
3 O
% O
Chinese O
, O
31 O
% O
Malays O
, O
and O
3 O
. O
7 O
% O
Indians O
and O
other O
ethnic O
groups O
. O

Eighty O
- O
one O
percent O
of O
patients O
with O
dyskinesia O
had O
clinical O
fluctuations O
. O

Patients O
with O
dyskinesia O
had O
lower O
onset O
age O
( O
p O
< O
0 O
. O
001 O
) O
, O
longer O
duration O
of O
levodopa B
therapy O
( O
p O
< O
0 O
. O
001 O
) O
, O
longer O
disease O
duration O
( O
p O
< O
0 O
. O
001 O
) O
, O
higher O
total O
daily O
levodopa B
dose O
( O
p O
< O
0 O
. O
001 O
) O
, O
and O
higher O
total O
UPDRS O
scores O
( O
p O
= O
0 O
. O
005 O
) O
than O
patients O
without O
dyskinesia O
. O

The O
three O
significant O
predictors O
of O
dyskinesia O
were O
duration O
of O
levodopa B
therapy O
, O
onset O
age O
, O
and O
total O
daily O
levodopa B
dose O
. O

CONCLUSIONS O
: O
The O
prevalence O
of O
levodopa B
- O
induced O
dyskinesia O
in O
our O
patients O
was O
44 O
% O
. O

The O
most O
significant O
predictors O
were O
duration O
of O
levodopa B
therapy O
, O
total O
daily O
levodopa B
dose O
, O
and O
onset O
age O
. O

Dose O
- O
dependent O
neurotoxicity O
of O
high O
- O
dose O
busulfan B
in O
children O
: O
a O
clinical O
and O
pharmacological O
study O
. O

Busulfan B
is O
known O
to O
be O
neurotoxic O
in O
animals O
and O
humans O
, O
but O
its O
acute O
neurotoxicity O
remains O
poorly O
characterized O
in O
children O
. O

We O
report O
here O
a O
retrospective O
study O
of O
123 O
children O
( O
median O
age O
, O
6 O
. O
5 O
years O
) O
receiving O
high O
- O
dose O
busulfan B
in O
combined O
chemotherapy O
before O
bone O
marrow O
transplantation O
for O
malignant O
solid O
tumors O
, O
brain O
tumors O
excluded O
. O

Busulfan B
was O
given O
p O
. O
o O
. O
, O
every O
6 O
hours O
for O
16 O
doses O
over O
4 O
days O
. O

Two O
total O
doses O
were O
consecutively O
used O
: O
16 O
mg O
/ O
kg O
, O
then O
600 O
mg O
/ O
m2 O
. O

The O
dose O
calculation O
on O
the O
basis O
of O
body O
surface O
area O
results O
in O
higher O
doses O
in O
young O
children O
than O
in O
older O
patients O
( O
16 O
to O
28 O
mg O
/ O
kg O
) O
. O

Ninety O
- O
six O
patients O
were O
not O
given O
anticonvulsive O
prophylaxis O
; O
7 O
( O
7 O
. O
5 O
% O
) O
developed O
seizures O
during O
the O
4 O
days O
of O
the O
busulfan B
course O
or O
within O
24 O
h O
after O
the O
last O
dosing O
. O

When O
the O
total O
busulfan B
dose O
was O
taken O
into O
account O
, O
there O
was O
a O
significant O
difference O
in O
terms O
of O
neurotoxicity O
incidence O
among O
patients O
under O
16 O
mg O
/ O
kg O
( O
1 O
of O
57 O
, O
1 O
. O
7 O
% O
) O
and O
patients O
under O
600 O
mg O
/ O
m2 O
( O
6 O
of O
39 O
, O
15 O
. O
4 O
% O
) O
( O
P O
less O
than O
0 O
. O
02 O
) O
. O

Twenty O
- O
seven O
patients O
were O
given O
a O
600 O
- O
mg O
/ O
m2 O
busulfan B
total O
dose O
with O
continuous O
i O
. O
v O
. O
infusion O
of O
clonazepam B
; O
none O
had O
any O
neurological O
symptoms O
. O

Busulfan B
levels O
were O
measured O
by O
a O
gas O
chromatographic O
- O
mass O
spectrometry O
assay O
in O
the O
plasma O
and O
cerebrospinal O
fluid O
of O
9 O
children O
without O
central O
nervous O
system O
disease O
under O
600 O
mg O
/ O
m2 O
busulfan B
with O
clonazepam B
: O
busulfan B
cerebrospinal O
fluid O
: O
plasma O
ratio O
was O
1 O
. O
39 O
. O

This O
was O
significantly O
different O
( O
P O
less O
than O
0 O
. O
02 O
) O
from O
the O
cerebrospinal O
fluid O
: O
plasma O
ratio O
previously O
defined O
in O
children O
receiving O
a O
16 O
- O
mg O
/ O
kg O
total O
dose O
of O
busulfan B
. O

This O
study O
shows O
that O
busulfan B
neurotoxicity O
is O
dose O
- O
dependent O
in O
children O
and O
efficiently O
prevented O
by O
clonazepam B
. O

A O
busulfan B
dose O
calculated O
on O
the O
basis O
of O
body O
surface O
area O
, O
resulting O
in O
higher O
doses O
in O
young O
children O
, O
was O
followed O
by O
increased O
neurotoxicity O
, O
close O
to O
neurotoxicity O
incidence O
observed O
in O
adults O
. O

Since O
plasma O
pharmacokinetic O
studies O
showed O
a O
faster O
busulfan B
clearance O
in O
children O
than O
in O
adults O
, O
this O
new O
dose O
may O
approximate O
more O
closely O
the O
adult O
systemic O
exposure O
obtained O
after O
the O
usual O
16 O
- O
mg O
/ O
kg O
total O
dose O
, O
with O
potential O
inferences O
in O
terms O
of O
anticancer O
or O
myeloablative O
effects O
. O

The O
busulfan B
dose O
in O
children O
and O
infants O
undergoing O
bone O
marrow O
transplantation O
should O
be O
reconsidered O
on O
the O
basis O
of O
pharmacokinetic O
studies O
. O

An O
unexpected O
diagnosis O
in O
a O
renal O
- O
transplant O
patient O
with O
proteinuria O
treated O
with O
everolimus B
: O
AL O
amyloidosis O
. O

Proteinuria O
is O
an O
expected O
complication O
in O
transplant O
patients O
treated O
with O
mammalian O
target O
of O
rapamycin B
inhibitors O
( O
mTOR O
- O
i O
) O
. O

However O
, O
clinical O
suspicion O
should O
always O
be O
supported O
by O
histological O
evidence O
in O
order O
to O
investigate O
potential O
alternate O
diagnoses O
such O
as O
acute O
or O
chronic O
rejection O
, O
interstitial O
fibrosis O
and O
tubular O
atrophy O
, O
or O
recurrent O
or O
de O
novo O
glomerulopathy O
. O

In O
this O
case O
we O
report O
the O
unexpected O
diagnosis O
of O
amyloidosis O
in O
a O
renal O
- O
transplant O
patient O
with O
pre O
- O
transplant O
monoclonal O
gammapathy O
of O
undetermined O
significance O
who O
developed O
proteinuria O
after O
conversion O
from O
tacrolimus B
to O
everolimus B
. O

Long O
- O
term O
oral O
galactose B
treatment O
prevents O
cognitive O
deficits O
in O
male O
Wistar O
rats O
treated O
intracerebroventricularly O
with O
streptozotocin B
. O

Basic O
and O
clinical O
research O
has O
demonstrated O
that O
dementia O
of O
sporadic O
Alzheimer O
' O
s O
disease O
( O
sAD O
) O
type O
is O
associated O
with O
dysfunction O
of O
the O
insulin O
- O
receptor O
( O
IR O
) O
system O
followed O
by O
decreased O
glucose B
transport O
via O
glucose B
transporter O
GLUT4 O
and O
decreased O
glucose B
metabolism O
in O
brain O
cells O
. O

An O
alternative O
source O
of O
energy O
is O
d B
- I
galactose I
( O
the O
C O
- O
4 O
- O
epimer O
of O
d B
- I
glucose I
) O
which O
is O
transported O
into O
the O
brain O
by O
insulin O
- O
independent O
GLUT3 O
transporter O
where O
it O
might O
be O
metabolized O
to O
glucose B
via O
the O
Leloir O
pathway O
. O

Exclusively O
parenteral O
daily O
injections O
of O
galactose B
induce O
memory O
deterioration O
in O
rodents O
and O
are O
used O
to O
generate O
animal O
aging O
model O
, O
but O
the O
effects O
of O
oral O
galactose B
treatment O
on O
cognitive O
functions O
have O
never O
been O
tested O
. O

We O
have O
investigated O
the O
effects O
of O
continuous O
daily O
oral O
galactose B
( O
200 O
mg O
/ O
kg O
/ O
day O
) O
treatment O
on O
cognitive O
deficits O
in O
streptozotocin B
- O
induced O
( O
STZ B
- O
icv O
) O
rat O
model O
of O
sAD O
, O
tested O
by O
Morris O
Water O
Maze O
and O
Passive O
Avoidance O
test O
, O
respectively O
. O

One O
month O
of O
oral O
galactose B
treatment O
initiated O
immediately O
after O
the O
STZ B
- O
icv O
administration O
, O
successfully O
prevented O
development O
of O
the O
STZ B
- O
icv O
- O
induced O
cognitive O
deficits O
. O

Beneficial O
effect O
of O
oral O
galactose B
was O
independent O
of O
the O
rat O
age O
and O
of O
the O
galactose B
dose O
ranging O
from O
100 O
to O
300 O
mg O
/ O
kg O
/ O
day O
. O

Additionally O
, O
oral O
galactose B
administration O
led O
to O
the O
appearance O
of O
galactose B
in O
the O
blood O
. O

The O
increase O
of O
galactose B
concentration O
in O
the O
cerebrospinal O
fluid O
was O
several O
times O
lower O
after O
oral O
than O
after O
parenteral O
administration O
of O
the O
same O
galactose B
dose O
. O

Oral O
galactose B
exposure O
might O
have O
beneficial O
effects O
on O
learning O
and O
memory O
ability O
and O
could O
be O
worth O
investigating O
for O
improvement O
of O
cognitive O
deficits O
associated O
with O
glucose B
hypometabolism O
in O
AD O
. O

An O
investigation O
of O
the O
pattern O
of O
kidney O
injury O
in O
HIV O
- O
positive O
persons O
exposed O
to O
tenofovir B
disoproxil I
fumarate I
: O
an O
examination O
of O
a O
large O
population O
database O
( O
MHRA O
database O
) O
. O

The O
potential O
for O
tenofovir B
to O
cause O
a O
range O
of O
kidney O
syndromes O
has O
been O
established O
from O
mechanistic O
and O
randomised O
clinical O
trials O
. O

However O
, O
the O
exact O
pattern O
of O
kidney O
involvement O
is O
still O
uncertain O
. O

We O
undertook O
a O
descriptive O
analysis O
of O
Yellow O
Card O
records O
of O
407 O
HIV O
- O
positive O
persons O
taking O
tenofovir B
disoproxil I
fumarate I
( O
TDF B
) O
as O
part O
of O
their O
antiretroviral O
therapy O
regimen O
and O
submitted O
to O
the O
Medicines O
and O
Healthcare O
Products O
Regulatory O
Agency O
( O
MHRA O
) O
with O
suspected O
kidney O
adverse O
effects O
. O

Reports O
that O
satisfy O
defined O
criteria O
were O
classified O
as O
acute O
kidney O
injury O
, O
kidney O
tubular O
dysfunction O
and O
Fanconi O
syndrome O
. O

Of O
the O
407 O
Yellow O
Card O
records O
analysed O
, O
106 O
satisfied O
criteria O
for O
TDF B
- O
related O
kidney O
disease O
, O
of O
which O
53 O
( O
50 O
% O
) O
had O
features O
of O
kidney O
tubular O
dysfunction O
, O
35 O
( O
33 O
% O
) O
were O
found O
to O
have O
features O
of O
glomerular O
dysfunction O
and O
18 O
( O
17 O
% O
) O
had O
Fanconi O
syndrome O
. O

The O
median O
TDF B
exposure O
was O
316 O
days O
( O
interquartile O
range O
120 O
- O
740 O
) O
. O

The O
incidence O
of O
hospitalisation O
for O
TDF B
kidney O
adverse O
effects O
was O
high O
, O
particularly O
amongst O
patients O
with O
features O
of O
Fanconi O
syndrome O
. O

The O
pattern O
of O
kidney O
syndromes O
in O
this O
population O
series O
mirrors O
that O
reported O
in O
randomised O
clinical O
trials O
. O

Cessation O
of O
TDF O
was O
associated O
with O
complete O
restoration O
of O
kidney O
function O
in O
up O
half O
of O
the O
patients O
in O
this O
report O
. O

Incidence O
of O
postoperative O
delirium O
is O
high O
even O
in O
a O
population O
without O
known O
risk O
factors O
. O

PURPOSE O
: O
Postoperative O
delirium O
is O
a O
recognized O
complication O
in O
populations O
at O
risk O
. O

The O
aim O
of O
this O
study O
is O
to O
assess O
the O
prevalence O
of O
early O
postoperative O
delirium O
in O
a O
population O
without O
known O
risk O
factors O
admitted O
to O
the O
ICU O
for O
postoperative O
monitoring O
after O
elective O
major O
surgery O
. O

The O
secondary O
outcome O
investigated O
is O
to O
identify O
eventual O
independent O
risk O
factors O
among O
demographic O
data O
and O
anesthetic O
drugs O
used O
. O

METHODS O
: O
An O
observational O
, O
prospective O
study O
was O
conducted O
on O
a O
consecutive O
cohort O
of O
patients O
admitted O
to O
our O
ICU O
within O
and O
for O
at O
least O
24 O
h O
after O
major O
surgical O
procedures O
. O

Exclusion O
criteria O
were O
any O
preexisting O
predisposing O
factor O
for O
delirium O
or O
other O
potentially O
confounding O
neurological O
dysfunctions O
. O

Patients O
were O
assessed O
daily O
using O
the O
confusion O
assessment O
method O
for O
the O
ICU O
scale O
for O
3 O
days O
after O
the O
surgical O
procedure O
. O

Early O
postoperative O
delirium O
incidence O
risk O
factors O
were O
then O
assessed O
through O
three O
different O
multiple O
regression O
models O
. O

RESULTS O
: O
According O
to O
the O
confusion O
assessment O
method O
for O
the O
ICU O
scale O
, O
28 O
% O
of O
patients O
were O
diagnosed O
with O
early O
postoperative O
delirium O
. O

The O
use O
of O
thiopentone B
was O
significantly O
associated O
with O
an O
eight O
- O
fold O
- O
higher O
risk O
for O
delirium O
compared O
to O
propofol B
( O
57 O
. O
1 O
% O
vs O
. O
7 O
. O
1 O
% O
, O
RR O
= O
8 O
. O
0 O
, O
X2 O
= O
4 O
. O
256 O
; O
df O
= O
1 O
; O
0 O
. O
05 O
< O
p O
< O
0 O
. O
02 O
) O
. O

CONCLUSION O
: O
In O
this O
study O
early O
postoperative O
delirium O
was O
found O
to O
be O
a O
very O
common O
complication O
after O
major O
surgery O
, O
even O
in O
a O
population O
without O
known O
risk O
factors O
. O

Thiopentone B
was O
independently O
associated O
with O
an O
increase O
in O
its O
relative O
risk O
. O

A O
single O
neurotoxic O
dose O
of O
methamphetamine B
induces O
a O
long O
- O
lasting O
depressive O
- O
like O
behaviour O
in O
mice O
. O

Methamphetamine B
( O
METH B
) O
triggers O
a O
disruption O
of O
the O
monoaminergic O
system O
and O
METH B
abuse O
leads O
to O
negative O
emotional O
states O
including O
depressive O
symptoms O
during O
drug O
withdrawal O
. O

However O
, O
it O
is O
currently O
unknown O
if O
the O
acute O
toxic O
dosage O
of O
METH B
also O
causes O
a O
long O
- O
lasting O
depressive O
phenotype O
and O
persistent O
monoaminergic O
deficits O
. O

Thus O
, O
we O
now O
assessed O
the O
depressive O
- O
like O
behaviour O
in O
mice O
at O
early O
and O
long O
- O
term O
periods O
following O
a O
single O
high O
METH B
dose O
( O
30 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
. O

METH B
did O
not O
alter O
the O
motor O
function O
and O
procedural O
memory O
of O
mice O
as O
assessed O
by O
swimming O
speed O
and O
escape O
latency O
to O
find O
the O
platform O
in O
a O
cued O
version O
of O
the O
water O
maze O
task O
. O

However O
, O
METH B
significantly O
increased O
the O
immobility O
time O
in O
the O
tail O
suspension O
test O
at O
3 O
and O
49 O
days O
post O
- O
administration O
. O

This O
depressive O
- O
like O
profile O
induced O
by O
METH B
was O
accompanied O
by O
a O
marked O
depletion O
of O
frontostriatal O
dopaminergic O
and O
serotonergic O
neurotransmission O
, O
indicated O
by O
a O
reduction O
in O
the O
levels O
of O
dopamine B
, O
DOPAC B
and O
HVA B
, O
tyrosine B
hydroxylase O
and O
serotonin B
, O
observed O
at O
both O
3 O
and O
49 O
days O
post O
- O
administration O
. O

In O
parallel O
, O
another O
neurochemical O
feature O
of O
depression O
- O
- O
astroglial O
dysfunction O
- O
- O
was O
unaffected O
in O
the O
cortex O
and O
the O
striatal O
levels O
of O
the O
astrocytic O
protein O
marker O
, O
glial O
fibrillary O
acidic O
protein O
, O
were O
only O
transiently O
increased O
at O
3 O
days O
. O

These O
findings O
demonstrate O
for O
the O
first O
time O
that O
a O
single O
high O
dose O
of O
METH B
induces O
long O
- O
lasting O
depressive O
- O
like O
behaviour O
in O
mice O
associated O
with O
a O
persistent O
disruption O
of O
frontostriatal O
dopaminergic O
and O
serotonergic O
homoeostasis O
. O

Linezolid B
- O
induced O
optic O
neuropathy O
. O

Many O
systemic O
antimicrobials O
have O
been O
implicated O
to O
cause O
ocular O
adverse O
effects O
. O

This O
is O
especially O
relevant O
in O
multidrug O
therapy O
where O
more O
than O
one O
drug O
can O
cause O
a O
similar O
ocular O
adverse O
effect O
. O

We O
describe O
a O
case O
of O
progressive O
loss O
of O
vision O
associated O
with O
linezolid B
therapy O
. O

A O
45 O
- O
year O
- O
old O
male O
patient O
who O
was O
on O
treatment O
with O
multiple O
second O
- O
line O
anti O
- O
tuberculous O
drugs O
including O
linezolid B
and O
ethambutol B
for O
extensively O
drug O
- O
resistant O
tuberculosis O
( O
XDR O
- O
TB O
) O
presented O
to O
us O
with O
painless O
progressive O
loss O
of O
vision O
in O
both O
eyes O
. O

Color O
vision O
was O
defective O
and O
fundus O
examination O
revealed O
optic O
disc O
edema O
in O
both O
eyes O
. O

Ethambutol B
- O
induced O
toxic O
optic O
neuropathy O
was O
suspected O
and O
tablet O
ethambutol B
was O
withdrawn O
. O

Deterioration O
of O
vision O
occurred O
despite O
withdrawal O
of O
ethambutol B
. O

Discontinuation O
of O
linezolid B
resulted O
in O
marked O
improvement O
of O
vision O
. O

Our O
report O
emphasizes O
the O
need O
for O
monitoring O
of O
visual O
function O
in O
patients O
on O
long O
- O
term O
linezolid B
treatment O
. O

Resuscitation O
with O
lipid O
, O
epinephrine B
, O
or O
both O
in O
levobupivacaine B
- O
induced O
cardiac O
toxicity O
in O
newborn O
piglets O
. O

BACKGROUND O
: O
The O
optimal O
dosing O
regimens O
of O
lipid O
emulsion O
, O
epinephrine B
, O
or O
both O
are O
not O
yet O
determined O
in O
neonates O
in O
cases O
of O
local O
anaesthetic O
systemic O
toxicity O
( O
LAST O
) O
. O

METHODS O
: O
Newborn O
piglets O
received O
levobupivacaine B
until O
cardiovascular O
collapse O
occurred O
. O

Standard O
cardiopulmonary O
resuscitation O
was O
started O
and O
electrocardiogram O
( O
ECG O
) O
was O
monitored O
for O
ventricular O
tachycardia O
, O
fibrillation O
, O
or O
QRS O
prolongation O
. O

Piglets O
were O
then O
randomly O
allocated O
to O
four O
groups O
: O
control O
( O
saline O
) O
, O
Intralipid B
( O
) O
alone O
, O
epinephrine B
alone O
, O
or O
a O
combination O
of O
Intralipd B
plus O
epinephrine B
. O

Resuscitation O
continued O
for O
30 O
min O
or O
until O
there O
was O
a O
return O
of O
spontaneous O
circulation O
( O
ROSC O
) O
accompanied O
by O
a O
mean O
arterial O
pressure O
at O
or O
superior O
to O
the O
baseline O
pressure O
and O
normal O
sinus O
rhythm O
for O
a O
period O
of O
30 O
min O
. O

RESULTS O
: O
ROSC O
was O
achieved O
in O
only O
one O
of O
the O
control O
piglets O
compared O
with O
most O
of O
the O
treated O
piglets O
. O

Mortality O
was O
not O
significantly O
different O
between O
the O
three O
treatment O
groups O
, O
but O
was O
significantly O
lower O
in O
all O
the O
treatment O
groups O
compared O
with O
control O
. O

The O
number O
of O
ECG O
abnormalities O
was O
zero O
in O
the O
Intralipid B
only O
group O
, O
but O
14 O
and O
17 O
, O
respectively O
, O
in O
the O
epinephrine B
and O
epinephrine B
plus O
lipid O
groups O
( O
P O
< O
0 O
. O
05 O
) O
. O

CONCLUSIONS O
: O
Lipid O
emulsion O
with O
or O
without O
epinephrine B
, O
or O
epinephrine B
alone O
were O
equally O
effective O
in O
achieving O
a O
return O
to O
spontaneous O
circulation O
in O
this O
model O
of O
LAST O
. O

Epinephrine B
alone O
or O
in O
combination O
with O
lipid O
was O
associated O
with O
an O
increased O
number O
of O
ECG O
abnormalities O
compared O
with O
lipid O
emulsion O
alone O
. O

Incidence O
of O
heparin B
- O
induced O
thrombocytopenia O
type O
II O
and O
postoperative O
recovery O
of O
platelet O
count O
in O
liver O
graft O
recipients O
: O
a O
retrospective O
cohort O
analysis O
. O

BACKGROUND O
: O
Thrombocytopenia O
in O
patients O
with O
end O
- O
stage O
liver O
disease O
is O
a O
common O
disorder O
caused O
mainly O
by O
portal O
hypertension O
, O
low O
levels O
of O
thrombopoetin O
, O
and O
endotoxemia O
. O

The O
impact O
of O
immune O
- O
mediated O
heparin B
- O
induced O
thrombocytopenia O
type O
II O
( O
HIT O
type O
II O
) O
as O
a O
cause O
of O
thrombocytopenia O
after O
liver O
transplantation O
is O
not O
yet O
understood O
, O
with O
few O
literature O
citations O
reporting O
contradictory O
results O
. O

The O
aim O
of O
our O
study O
was O
to O
demonstrate O
the O
perioperative O
course O
of O
thrombocytopenia O
after O
liver O
transplantation O
and O
determine O
the O
occurrence O
of O
clinical O
HIT O
type O
II O
. O

METHOD O
: O
We O
retrospectively O
evaluated O
the O
medical O
records O
of O
205 O
consecutive O
adult O
patients O
who O
underwent O
full O
- O
size O
liver O
transplantation O
between O
January O
2006 O
and O
December O
2010 O
due O
to O
end O
- O
stage O
or O
malignant O
liver O
disease O
. O

Preoperative O
platelet O
count O
, O
postoperative O
course O
of O
platelets O
, O
and O
clinical O
signs O
of O
HIT O
type O
II O
were O
analyzed O
. O

RESULTS O
: O
A O
total O
of O
155 O
( O
75 O
. O
6 O
% O
) O
of O
205 O
patients O
had O
thrombocytopenia O
before O
transplantation O
, O
significantly O
influenced O
by O
Model O
of O
End O
- O
Stage O
Liver O
Disease O
score O
and O
liver O
cirrhosis O
. O

The O
platelet O
count O
exceeded O
100 O
, O
000 O
/ O
uL O
in O
most O
of O
the O
patients O
( O
n O
= O
193 O
) O
at O
a O
medium O
of O
7 O
d O
. O

Regarding O
HIT O
II O
, O
there O
were O
four O
( O
1 O
. O
95 O
% O
) O
patients O
with O
a O
background O
of O
HIT O
type O
II O
. O

CONCLUSIONS O
: O
The O
incidence O
of O
HIT O
in O
patients O
with O
end O
- O
stage O
hepatic O
failure O
is O
, O
with O
about O
1 O
. O
95 O
% O
, O
rare O
. O

For O
further O
reduction O
of O
HIT O
type O
II O
, O
the O
use O
of O
intravenous O
heparin B
should O
be O
avoided O
and O
the O
prophylactic O
anticoagulation O
should O
be O
performed O
with O
low B
- I
molecular I
- I
weight I
heparin I
after O
normalization O
of O
platelet O
count O
. O

Takotsubo O
syndrome O
( O
or O
apical O
ballooning O
syndrome O
) O
secondary O
to O
Zolmitriptan B
. O

Takotsubo O
syndrome O
( O
TS O
) O
, O
also O
known O
as O
broken O
heart O
syndrome O
, O
is O
characterized O
by O
left O
ventricle O
apical O
ballooning O
with O
elevated O
cardiac O
biomarkers O
and O
electrocardiographic O
changes O
suggestive O
of O
an O
acute O
coronary O
syndrome O
( O
ie O
, O
ST O
- O
segment O
elevation O
, O
T O
wave O
inversions O
, O
and O
pathologic O
Q O
waves O
) O
. O

We O
report O
a O
case O
of O
54 O
- O
year O
- O
old O
woman O
with O
medical O
history O
of O
mitral O
valve O
prolapse O
and O
migraines O
, O
who O
was O
admitted O
to O
the O
hospital O
for O
substernal O
chest O
pain O
and O
electrocardiogram O
demonstrated O
1 O
/ O
2 O
mm O
ST O
- O
segment O
elevation O
in O
leads O
II O
, O
III O
, O
aVF O
, O
V5 O
, O
and O
V6 O
and O
positive O
troponin O
I O
. O

Emergent O
coronary O
angiogram O
revealed O
normal O
coronary O
arteries O
with O
moderately O
reduced O
left O
ventricular O
ejection O
fraction O
with O
wall O
motion O
abnormalities O
consistent O
with O
TS O
. O

Detailed O
history O
obtained O
retrospectively O
revealed O
that O
the O
patient O
took O
zolmitriptan B
sparingly O
only O
when O
she O
had O
migraines O
. O

But O
before O
this O
event O
, O
she O
was O
taking O
zolmitriptan B
2 O
- O
3 O
times O
daily O
for O
several O
days O
because O
of O
a O
persistent O
migraine O
headache O
. O

She O
otherwise O
reported O
that O
she O
is O
quite O
active O
, O
rides O
horses O
, O
and O
does O
show O
jumping O
without O
any O
limitations O
in O
her O
physical O
activity O
. O

There O
was O
no O
evidence O
of O
any O
recent O
stress O
or O
status O
migrainosus O
. O

Extensive O
literature O
search O
revealed O
multiple O
cases O
of O
coronary O
artery O
vasospasm O
secondary O
to O
zolmitriptan B
, O
but O
none O
of O
the O
cases O
were O
associated O
with O
TS O
. O

Depression O
, O
impulsiveness O
, O
sleep O
, O
and O
memory O
in O
past O
and O
present O
polydrug O
users O
of O
3 B
, I
4 I
- I
methylenedioxymethamphetamine I
( O
MDMA B
, O
ecstasy B
) O
. O

RATIONALE O
: O
Ecstasy B
( O
3 B
, I
4 I
- I
methylenedioxymethamphetamine I
, O
MDMA B
) O
is O
a O
worldwide O
recreational O
drug O
of O
abuse O
. O

Unfortunately O
, O
the O
results O
from O
human O
research O
investigating O
its O
psychological O
effects O
have O
been O
inconsistent O
. O

OBJECTIVES O
: O
The O
present O
study O
aimed O
to O
be O
the O
largest O
to O
date O
in O
sample O
size O
and O
5HT O
- O
related O
behaviors O
; O
the O
first O
to O
compare O
present O
ecstasy B
users O
with O
past O
users O
after O
an O
abstinence O
of O
4 O
or O
more O
years O
, O
and O
the O
first O
to O
include O
robust O
controls O
for O
other O
recreational O
substances O
. O

METHODS O
: O
A O
sample O
of O
997 O
participants O
( O
52 O
% O
male O
) O
was O
recruited O
to O
four O
control O
groups O
( O
non O
- O
drug O
( O
ND O
) O
, O
alcohol B
/ O
nicotine B
( O
AN O
) O
, O
cannabis B
/ O
alcohol B
/ O
nicotine B
( O
CAN O
) O
, O
non O
- O
ecstasy B
polydrug O
( O
PD O
) O
) O
, O
and O
two O
ecstasy B
polydrug O
groups O
( O
present O
( O
MDMA B
) O
and O
past O
users O
( O
EX O
- O
MDMA B
) O
. O

Participants O
completed O
a O
drug O
history O
questionnaire O
, O
Beck O
Depression O
Inventory O
, O
Barratt O
Impulsiveness O
Scale O
, O
Pittsburgh O
Sleep O
Quality O
Index O
, O
and O
Wechsler O
Memory O
Scale O
- O
Revised O
which O
, O
in O
total O
, O
provided O
13 O
psychometric O
measures O
. O

RESULTS O
: O
While O
the O
CAN O
and O
PD O
groups O
tended O
to O
record O
greater O
deficits O
than O
the O
non O
- O
drug O
controls O
, O
the O
MDMA B
and O
EX O
- O
MDMA B
groups O
recorded O
greater O
deficits O
than O
all O
the O
control O
groups O
on O
ten O
of O
the O
13 O
psychometric O
measures O
. O

Strikingly O
, O
despite O
prolonged O
abstinence O
( O
mean O
, O
4 O
. O
98 O
; O
range O
, O
4 O
- O
9 O
years O
) O
, O
past O
ecstasy B
users O
showed O
few O
signs O
of O
recovery O
. O

Compared O
with O
present O
ecstasy B
users O
, O
the O
past O
users O
showed O
no O
change O
for O
ten O
measures O
, O
increased O
impairment O
for O
two O
measures O
, O
and O
improvement O
on O
just O
one O
measure O
. O

CONCLUSIONS O
: O
Given O
this O
record O
of O
impaired O
memory O
and O
clinically O
significant O
levels O
of O
depression O
, O
impulsiveness O
, O
and O
sleep O
disturbance O
, O
the O
prognosis O
for O
the O
current O
generation O
of O
ecstasy B
users O
is O
a O
major O
cause O
for O
concern O
. O

Association O
of O
common O
genetic O
variants O
of O
HOMER1 O
gene O
with O
levodopa B
adverse O
effects O
in O
Parkinson O
' O
s O
disease O
patients O
. O

Levodopa B
is O
the O
most O
effective O
symptomatic O
therapy O
for O
Parkinson O
' O
s O
disease O
, O
but O
its O
chronic O
use O
could O
lead O
to O
chronic O
adverse O
outcomes O
, O
such O
as O
motor O
fluctuations O
, O
dyskinesia O
and O
visual O
hallucinations O
. O

HOMER1 O
is O
a O
protein O
with O
pivotal O
function O
in O
glutamate B
transmission O
, O
which O
has O
been O
related O
to O
the O
pathogenesis O
of O
these O
complications O
. O

This O
study O
investigates O
whether O
polymorphisms O
in O
the O
HOMER1 O
gene O
promoter O
region O
are O
associated O
with O
the O
occurrence O
of O
the O
chronic O
complications O
of O
levodopa B
therapy O
. O

A O
total O
of O
205 O
patients O
with O
idiopathic O
Parkinson O
' O
s O
disease O
were O
investigated O
. O

Patients O
were O
genotyped O
for O
rs4704559 O
, O
rs10942891 O
and O
rs4704560 O
by O
allelic O
discrimination O
with O
Taqman O
assays O
. O

The O
rs4704559 O
G O
allele O
was O
associated O
with O
a O
lower O
prevalence O
of O
dyskinesia O
( O
prevalence O
ratio O
( O
PR O
) O
= O
0 O
. O
615 O
, O
95 O
% O
confidence O
interval O
( O
CI O
) O
0 O
. O
426 O
- O
0 O
. O
887 O
, O
P O
= O
0 O
. O
009 O
) O
and O
visual O
hallucinations O
( O
PR O
= O
0 O
. O
515 O
, O
95 O
% O
CI O
0 O
. O
295 O
- O
0 O
. O
899 O
, O
P O
= O
0 O
. O
020 O
) O
. O

Our O
data O
suggest O
that O
HOMER1 O
rs4704559 O
G O
allele O
has O
a O
protective O
role O
for O
the O
development O
of O
levodopa B
adverse O
effects O
. O

Crocin B
improves O
lipid O
dysregulation O
in O
subacute O
diazinon B
exposure O
through O
ERK1 O
/ O
2 O
pathway O
in O
rat O
liver O
. O

INTRODUCTION O
: O
Diazinon B
Yis I
one O
of O
the O
most O
broadly O
used O
organophosphorus B
insecticides O
in O
agriculture O
. O

It O
has O
been O
shown O
that O
exposure O
to O
diazinon B
may O
interfere O
with O
lipid O
metabolism O
. O

Moreover O
, O
the O
hypolipidemic O
effect O
of O
crocin B
has O
been O
established O
. O

Earlier O
studies O
revealed O
the O
major O
role O
of O
Extracellular O
signal O
- O
regulated O
kinase O
( O
ERK O
) O
pathways O
in O
low O
- O
density O
lipoprotein O
receptor O
( O
LDLr O
) O
expression O
. O

The O
aim O
of O
this O
study O
was O
to O
evaluate O
changes O
in O
the O
regulation O
of O
lipid O
metabolism O
, O
ERK O
and O
LDLr O
expression O
in O
the O
liver O
of O
rats O
exposed O
to O
subacute O
diazinon B
. O

Furthermore O
ameliorating O
effect O
of O
crocin B
on O
diazinon B
induced O
disturbed O
cholesterol B
homeostasis O
was O
studied O
. O

METHODS O
: O
24 O
Rats O
were O
divided O
into O
4 O
groups O
and O
received O
following O
treatments O
for O
4 O
weeks O
; O
Corn O
oil O
( O
control O
) O
, O
diazinon B
( O
15mg O
/ O
kg O
per O
day O
, O
orally O
) O
and O
crocin B
( O
12 O
. O
5 O
and O
25mg O
/ O
kg O
per O
day O
, O
intraperitoneally O
) O
in O
combination O
with O
diazinon B
( O
15 O
mg O
/ O
kg O
) O
. O

The O
levels O
of O
cholesterol B
, O
triglyceride B
and O
LDL O
in O
blood O
of O
rats O
were O
analyzed O
. O

Moreover O
mRNA O
levels O
of O
LDLr O
and O
ERK1 O
/ O
2 O
as O
well O
as O
protein O
levels O
of O
total O
and O
activated O
forms O
of O
ERK1 O
/ O
2 O
in O
rat O
liver O
were O
evaluated O
by O
Western O
blotting O
and O
quantitative O
real O
time O
polymerase O
chain O
reaction O
analysis O
. O

RESULTS O
: O
Our O
data O
showed O
that O
subacute O
exposure O
to O
diazinon B
significantly O
increased O
concentrations O
of O
cholesterol B
, O
triglyceride B
and O
LDL O
. O

Moreover O
diazinon B
decreased O
ERK1 O
/ O
2 O
protein O
phosphorylation O
and O
LDLr O
transcript O
. O

Crocin B
reduced O
inhibition O
of O
ERK O
activation O
and O
diazinon B
- O
induced O
hyperlipemia O
and O
increased O
levels O
of O
LDLr O
transcript O
. O

CONCLUSIONS O
: O
Crocin B
may O
be O
considered O
as O
a O
novel O
protective O
agent O
in O
diazinon B
- O
induced O
hyperlipemia O
through O
modulating O
of O
ERK O
pathway O
and O
increase O
of O
LDLr O
expression O
. O

GEM B
- I
P I
chemotherapy O
is O
active O
in O
the O
treatment O
of O
relapsed O
Hodgkin O
lymphoma O
. O

Hodgkin O
lymphoma O
( O
HL O
) O
is O
a O
relatively O
chemosensitive O
malignancy O
. O

However O
, O
for O
those O
who O
relapse O
, O
high O
- O
dose O
chemotherapy O
with O
autologous O
stem O
cell O
transplant O
is O
the O
treatment O
of O
choice O
which O
relies O
on O
adequate O
disease O
control O
with O
salvage O
chemotherapy O
. O

Regimens O
commonly O
used O
often O
require O
inpatient O
administration O
and O
can O
be O
difficult O
to O
deliver O
due O
to O
toxicity O
. O

Gemcitabine B
and O
cisplatin B
have O
activity O
in O
HL O
, O
non O
- O
overlapping O
toxicity O
with O
first O
- O
line O
chemotherapeutics O
, O
and O
may O
be O
delivered O
in O
an O
outpatient O
setting O
. O

In O
this O
retrospective O
single O
- O
centre O
analysis O
, O
patients O
with O
relapsed O
or O
refractory O
HL O
treated O
with O
gemcitabine B
1 O
, O
000 O
mg O
/ O
m O
( O
2 O
) O
day O
( O
D O
) O
1 O
, O
D8 O
and O
D15 O
; O
methylprednisolone B
1 O
, O
000 O
mg O
D1 O
- O
5 O
; O
and O
cisplatin B
100 O
mg O
/ O
m O
( O
2 O
) O
D15 O
, O
every O
28 O
days O
( O
GEM B
- O
P O
) O
were O
included O
. O

Demographic O
, O
survival O
, O
response O
and O
toxicity O
data O
were O
recorded O
. O

Forty O
- O
one O
eligible O
patients O
were O
identified O
: O
median O
age O
27 O
. O

One O
hundred O
and O
twenty O
- O
two O
cycles O
of O
GEM B
- I
P I
were O
administered O
in O
total O
( O
median O
3 O
cycles O
; O
range O
1 O
- O
6 O
) O
. O

Twenty O
of O
41 O
( O
48 O
% O
) O
patients O
received O
GEM B
- I
P I
as O
second O
- O
line O
treatment O
and O
11 O
/ O
41 O
( O
27 O
% O
) O
as O
third O
- O
line O
therapy O
. O

Overall O
response O
rate O
( O
ORR O
) O
to O
GEM B
- I
P I
in O
the O
entire O
cohort O
was O
80 O
% O
( O
complete O
response O
( O
CR O
) O
37 O
% O
, O
partial O
response O
44 O
% O
) O
with O
14 O
/ O
15 O
CR O
confirmed O
as O
a O
metabolic O
CR O
on O
PET O
and O
ORR O
of O
85 O
% O
in O
the O
20 O
second O
- O
line O
patients O
. O

The O
most O
common O
grade O
3 O
/ O
4 O
toxicities O
were O
haematological O
: O
neutropenia O
54 O
% O
and O
thrombocytopenia O
51 O
% O
. O

Median O
follow O
- O
up O
from O
the O
start O
of O
GEM B
- I
P I
was O
4 O
. O
5 O
years O
. O

Following O
GEM B
- I
P I
, O
5 O
- O
year O
progression O
- O
free O
survival O
was O
46 O
% O
( O
95 O
% O
confidence O
interval O
( O
CI O
) O
, O
30 O
- O
62 O
% O
) O
and O
5 O
- O
year O
overall O
survival O
was O
59 O
% O
( O
95 O
% O
CI O
, O
43 O
- O
74 O
% O
) O
. O

Fourteen O
of O
41 O
patients O
proceeded O
directly O
to O
autologous O
transplant O
. O

GEM B
- I
P I
is O
a O
salvage O
chemotherapy O
with O
relatively O
high O
response O
rates O
, O
leading O
to O
successful O
transplantation O
in O
appropriate O
patients O
, O
in O
the O
treatment O
of O
relapsed O
or O
refractory O
HL O
. O

Basal O
functioning O
of O
the O
hypothalamic O
- O
pituitary O
- O
adrenal O
( O
HPA O
) O
axis O
and O
psychological O
distress O
in O
recreational O
ecstasy B
polydrug O
users O
. O

RATIONALE O
: O
Ecstasy B
( O
MDMA B
) O
is O
a O
psychostimulant O
drug O
which O
is O
increasingly O
associated O
with O
psychobiological O
dysfunction O
. O

While O
some O
recent O
studies O
suggest O
acute O
changes O
in O
neuroendocrine O
function O
, O
less O
is O
known O
about O
long O
- O
term O
changes O
in O
HPA O
functionality O
in O
recreational O
users O
. O

OBJECTIVES O
: O
The O
current O
study O
is O
the O
first O
to O
explore O
the O
effects O
of O
ecstasy B
- O
polydrug O
use O
on O
psychological O
distress O
and O
basal O
functioning O
of O
the O
HPA O
axis O
through O
assessing O
the O
secretion O
of O
cortisol B
across O
the O
diurnal O
period O
. O

METHOD O
: O
Seventy O
- O
six O
participants O
( O
21 O
nonusers O
, O
29 O
light O
ecstasy B
- O
polydrug O
users O
, O
26 O
heavy O
ecstasy B
- O
polydrug O
users O
) O
completed O
a O
substance O
use O
inventory O
and O
measures O
of O
psychological O
distress O
at O
baseline O
, O
then O
two O
consecutive O
days O
of O
cortisol B
sampling O
( O
on O
awakening O
, O
30 O
min O
post O
awakening O
, O
between O
1400 O
and O
1600 O
hours O
and O
pre O
bedtime O
) O
. O

On O
day O
2 O
, O
participants O
also O
attended O
the O
laboratory O
to O
complete O
a O
20 O
- O
min O
multitasking O
stressor O
. O

RESULTS O
: O
Both O
user O
groups O
exhibited O
significantly O
greater O
levels O
of O
anxiety O
and O
depression O
than O
nonusers O
. O

On O
day O
1 O
, O
all O
participants O
exhibited O
a O
typical O
cortisol B
profile O
, O
though O
light O
users O
had O
significantly O
elevated O
levels O
pre O
- O
bed O
. O

On O
day O
2 O
, O
heavy O
users O
demonstrated O
elevated O
levels O
upon O
awakening O
and O
all O
ecstasy B
- O
polydrug O
users O
demonstrated O
elevated O
pre O
- O
bed O
levels O
compared O
to O
non O
- O
users O
. O

Significant O
between O
group O
differences O
were O
also O
observed O
in O
afternoon O
cortisol B
levels O
and O
in O
overall O
cortisol B
secretion O
across O
the O
day O
. O

CONCLUSIONS O
: O
The O
increases O
in O
anxiety O
and O
depression O
are O
in O
line O
with O
previous O
observations O
in O
recreational O
ecstasy B
- O
polydrug O
users O
. O

Dysregulated O
diurnal O
cortisol B
may O
be O
indicative O
of O
inappropriate O
anticipation O
of O
forthcoming O
demands O
and O
hypersecretion O
may O
lead O
to O
the O
increased O
psychological O
and O
physical O
morbidity O
associated O
with O
heavy O
recreational O
use O
of O
ecstasy B
. O

Ifosfamide B
related O
encephalopathy O
: O
the O
need O
for O
a O
timely O
EEG O
evaluation O
. O

BACKGROUND O
: O
Ifosfamide B
is O
an O
alkylating O
agent O
useful O
in O
the O
treatment O
of O
a O
wide O
range O
of O
cancers O
including O
sarcomas O
, O
lymphoma O
, O
gynecologic O
and O
testicular O
cancers O
. O

Encephalopathy O
has O
been O
reported O
in O
10 O
- O
40 O
% O
of O
patients O
receiving O
high O
- O
dose O
IV O
ifosfamide B
. O

OBJECTIVE O
: O
To O
highlight O
the O
role O
of O
electroencephalogram O
( O
EEG O
) O
in O
the O
early O
detection O
and O
management O
of O
ifosfamide B
related O
encephalopathy O
. O

METHODS O
: O
Retrospective O
chart O
review O
including O
clinical O
data O
and O
EEG O
recordings O
was O
done O
on O
five O
patients O
, O
admitted O
to O
MD O
Anderson O
Cancer O
Center O
between O
years O
2009 O
and O
2012 O
, O
who O
developed O
ifosfamide B
related O
acute O
encephalopathy O
. O

RESULTS O
: O
All O
five O
patients O
experienced O
symptoms O
of O
encephalopathy O
soon O
after O
( O
within O
12 O
h O
- O
2 O
days O
) O
receiving O
ifosfamide B
. O

Two O
patients O
developed O
generalized O
convulsions O
while O
one O
patient O
developed O
continuous O
non O
- O
convulsive O
status O
epilepticus O
( O
NCSE O
) O
that O
required O
ICU O
admission O
and O
intubation O
. O

Initial O
EEG O
showed O
epileptiform O
discharges O
in O
three O
patients O
; O
run O
of O
triphasic O
waves O
in O
one O
patient O
and O
moderate O
degree O
diffuse O
generalized O
slowing O
. O

Mixed O
pattern O
with O
the O
presence O
of O
both O
sharps O
and O
triphasic O
waves O
were O
also O
noted O
. O

Repeat O
EEGs O
within O
24 O
_ O
h O
of O
symptom O
onset O
showed O
marked O
improvement O
that O
was O
correlated O
with O
clinical O
improvement O
. O

CONCLUSIONS O
: O
Severity O
of O
ifosfamide B
related O
encephalopathy O
correlates O
with O
EEG O
changes O
. O

We O
suggest O
a O
timely O
EEG O
evaluation O
for O
patients O
receiving O
ifosfamide B
who O
develop O
features O
of O
encephalopathy O
. O

Incidence O
of O
contrast O
- O
induced O
nephropathy O
in O
hospitalised O
patients O
with O
cancer O
. O

OBJECTIVES O
: O
To O
determine O
the O
frequency O
of O
and O
possible O
factors O
related O
to O
contrast O
- O
induced O
nephropathy O
( O
CIN O
) O
in O
hospitalised O
patients O
with O
cancer O
. O

METHODS O
: O
Ninety O
adult O
patients O
were O
enrolled O
. O

Patients O
with O
risk O
factors O
for O
acute O
renal O
failure O
were O
excluded O
. O

Blood O
samples O
were O
examined O
the O
day O
before O
contrast O
- O
enhanced O
computed O
tomography O
( O
CT O
) O
and O
serially O
for O
3 O
days O
thereafter O
. O

CIN O
was O
defined O
as O
an O
increase O
in O
serum O
creatinine B
( O
Cr B
) O
of O
0 O
. O
5 O
mg O
/ O
dl O
or O
more O
, O
or O
elevation O
of O
Cr B
to O
25 O
% O
over O
baseline O
. O

Relationships O
between O
CIN O
and O
possible O
risk O
factors O
were O
investigated O
. O

RESULTS O
: O
CIN O
was O
detected O
in O
18 O
/ O
90 O
( O
20 O
% O
) O
patients O
. O

CIN O
developed O
in O
25 O
. O
5 O
% O
patients O
who O
underwent O
chemotherapy O
and O
in O
11 O
% O
patients O
who O
did O
not O
( O
P O
= O
0 O
. O
1 O
) O
. O

CIN O
more O
frequently O
developed O
in O
patients O
who O
had O
undergone O
CT O
within O
45 O
days O
after O
the O
last O
chemotherapy O
( O
P O
= O
0 O
. O
005 O
) O
; O
it O
was O
also O
an O
independent O
risk O
factor O
( O
P O
= O
0 O
. O
017 O
) O
. O

CIN O
was O
significantly O
more O
after O
treatment O
with O
bevacizumab B
/ O
irinotecan B
( O
P O
= O
0 O
. O
021 O
) O
and O
in O
patients O
with O
hypertension O
( O
P O
= O
0 O
. O
044 O
) O
. O

CONCLUSIONS O
: O
The O
incidence O
of O
CIN O
after O
CT O
in O
hospitalised O
oncological O
patients O
was O
20 O
% O
. O

CIN O
developed O
4 O
. O
5 O
- O
times O
more O
frequently O
in O
patients O
with O
cancer O
who O
had O
undergone O
recent O
chemotherapy O
. O

Hypertension O
and O
the O
combination O
of O
bevacizumab B
/ O
irinotecan B
may O
be O
additional O
risk O
factors O
for O
CIN O
development O
. O

KEY O
POINTS O
: O
. O

Contrast O
- O
induced O
nephropathy O
( O
CIN O
) O
is O
a O
concern O
for O
oncological O
patients O
undergoing O
CT O
. O

. O
CIN O
occurs O
more O
often O
when O
CT O
is O
performed O
< O
45 O
days O
after O
chemotherapy O
. O

. O
Hypertension O
and O
treatment O
with O
bevacizumab B
appear O
to O
be O
additional O
risk O
factors O
. O

Syndrome O
of O
inappropriate O
antidiuretic O
hormone O
secretion O
associated O
with O
desvenlafaxine B
. O

OBJECTIVE O
: O
To O
report O
a O
case O
of O
syndrome O
of O
inappropriate O
anti O
- O
diuretic O
hormone O
( O
SIADH O
) O
secretion O
associated O
with O
desvenlafaxine B
. O

CASE O
SUMMARY O
: O
A O
57 O
- O
year O
old O
female O
with O
hyponatraemia O
. O

Her O
medications O
included O
desvenlafaxine B
, O
and O
symptoms O
included O
nausea O
, O
anxiety O
and O
confusion O
. O

The O
serum O
sodium B
at O
this O
time O
was O
120 O
mmol O
/ O
L O
, O
serum O
osmolality O
was O
263 O
mosmol O
/ O
kg O
, O
urine O
osmolality O
410 O
mosmol O
/ O
kg O
and O
urine O
sodium B
63 O
mmol O
/ O
L O
, O
consistent O
with O
a O
diagnosis O
of O
SIADH O
. O

Desvenlafaxine B
was O
ceased O
and O
fluid O
restriction O
implemented O
. O

After O
4 O
days O
the O
sodium B
increased O
to O
128 O
mmol O
/ O
L O
and O
fluid O
restriction O
was O
relaxed O
. O

During O
her O
further O
3 O
weeks O
inpatient O
admission O
the O
serum O
sodium B
ranged O
from O
134 O
to O
137 O
mmol O
/ O
L O
during O
treatment O
with O
mirtazapine B
. O

DISCUSSION O
: O
SIADH O
has O
been O
widely O
reported O
with O
a O
range O
of O
antidepressants B
. O

This O
case O
report O
suggests O
that O
desvenlafaxine B
might O
cause O
clinically O
significant O
hyponatremia O
. O

CONCLUSIONS O
: O
Clinicians O
should O
be O
aware O
of O
the O
potential O
for O
antidepressants O
to O
cause O
hyponatremia O
, O
and O
take O
appropriate O
corrective O
action O
where O
necessary O
. O

Oxidative O
stress O
on O
cardiotoxicity O
after O
treatment O
with O
single O
and O
multiple O
doses O
of O
doxorubicin B
. O

The O
mechanism O
of O
doxorubicin B
( O
DOX B
) O
- O
induced O
cardiotoxicity O
remains O
controversial O
. O

Wistar O
rats O
( O
n O
= O
66 O
) O
received O
DOX B
injections O
intraperitoneally O
and O
were O
randomly O
assigned O
to O
2 O
experimental O
protocols O
: O
( O
1 O
) O
rats O
were O
killed O
before O
( O
- O
24 O
h O
, O
n O
= O
8 O
) O
and O
24 O
h O
after O
( O
+ O
24 O
h O
, O
n O
= O
8 O
) O
a O
single O
dose O
of O
DOX B
( O
4 O
mg O
/ O
kg O
body O
weight O
) O
to O
determine O
the O
DOX B
acute O
effect O
and O
( O
2 O
) O
rats O
( O
n O
= O
58 O
) O
received O
4 O
injections O
of O
DOX B
( O
4 O
mg O
/ O
kg O
body O
weight O
/ O
week O
) O
and O
were O
killed O
before O
the O
first O
injection O
( O
M0 O
) O
and O
1 O
week O
after O
each O
injection O
( O
M1 O
, O

M2 O
, O
M3 O
, O
and O
M4 O
) O
to O
determine O
the O
chronological O
effects O
. O

Animals O
used O
at O
M0 O
( O
n O
= O
8 O
) O
were O
also O
used O
at O
moment O
- O
24 O
h O
of O
acute O
study O
. O

Cardiac O
total O
antioxidant O
performance O
( O
TAP O
) O
, O
DNA O
damage O
, O
and O
morphology O
analyses O
were O
carried O
out O
at O
each O
time O
point O
. O

Single O
dose O
of O
DOX B
was O
associated O
with O
increased O
cardiac O
disarrangement O
, O
necrosis O
, O
and O
DNA O
damage O
( O
strand O
breaks O
( O
SBs O
) O
and O
oxidized O
pyrimidines B
) O
and O
decreased O
TAP O
. O

The O
chronological O
study O
showed O
an O
effect O
of O
a O
cumulative O
dose O
on O
body O
weight O
( O
R O
= O
- O
0 O
. O
99 O
, O
p O
= O
0 O
. O
011 O
) O
, O
necrosis O
( O
R O
= O
1 O
. O
00 O
, O
p O
= O
0 O
. O
004 O
) O
, O
TAP O
( O
R O
= O
0 O
. O
95 O
, O
p O
= O
0 O
. O
049 O
) O
, O
and O
DNA O
SBs O
( O
R O
= O
- O
0 O
. O
95 O
, O
p O
= O
0 O
. O
049 O
) O
. O

DNA O
SBs O
damage O
was O
negatively O
associated O
with O
TAP O
( O
R O
= O
- O
0 O
. O
98 O
, O
p O
= O
0 O
. O
018 O
) O
, O
and O
necrosis O
( O
R O
= O
- O
0 O
. O
97 O
, O
p O
= O
0 O
. O
027 O
) O
. O

Our O
results O
suggest O
that O
oxidative O
damage O
is O
associated O
with O
acute O
cardiotoxicity O
induced O
by O
a O
single O
dose O
of O
DOX B
only O
. O

Increased O
resistance O
to O
the O
oxidative O
stress O
is O
plausible O
for O
the O
multiple O
dose O
of O
DOX B
. O

Thus O
, O
different O
mechanisms O
may O
be O
involved O
in O
acute O
toxicity O
versus O
chronic O
toxicity O
. O

Tacrolimus B
- O
related O
seizure O
after O
pediatric O
liver O
transplantation O
- O
- O
a O
single O
- O
center O
experience O
. O

To O
identify O
the O
risk O
factors O
for O
new O
- O
onset O
seizures O
after O
pediatric O
LT O
and O
to O
assess O
their O
clinical O
implications O
and O
long O
- O
term O
prognosis O
. O

The O
clinical O
and O
laboratory O
data O
of O
27 O
consecutive O
children O
who O
underwent O
LT O
from O
January O
2007 O
to O
December O
2010 O
in O
our O
center O
were O
analyzed O
retrospectively O
. O

Patients O
were O
divided O
into O
seizures O
group O
and O
a O
non O
- O
seizures O
group O
. O

Pre O
- O
operative O
, O
intra O
- O
operative O
, O
and O
post O
- O
operative O
data O
were O
collected O
. O

Seizures O
occurred O
in O
four O
children O
, O
an O
incidence O
of O
14 O
. O
8 O
% O
. O

All O
exhibited O
generalized O
tonic O
- O
clonic O
seizures O
within O
the O
first O
two O
wk O
after O
LT B
. O

Univariate O
analysis O
showed O
that O
the O
risk O
factors O
associated O
with O
seizures O
after O
pediatric O
LT O
included O
gender O
, O
pediatric O
end O
- O
stage O
liver O
disease O
score O
before O
surgery O
, O
Child O
- O
Pugh O
score O
before O
surgery O
, O
serum O
total O
bilirubin B
after O
surgery O
, O
and O
trough O
TAC B
level O
. O

Multivariate O
analysis O
showed O
that O
trough O
TAC B
level O
was O
the O
only O
independent O
risk O
factor O
associated O
with O
the O
seizures O
. O

All O
children O
who O
experienced O
seizures O
survived O
with O
good O
graft O
function O
and O
remained O
seizure O
- O
free O
without O
anti O
- O
epileptic O
drugs O
over O
a O
mean O
follow O
- O
up O
period O
of O
33 O
. O
7 O
+ O
14 O
. O
6 O
months O
. O

High O
trough O
TAC B
level O
was O
the O
predominant O
factor O
that O
contributed O
to O
seizures O
in O
the O
early O
post O
- O
operative O
period O
after O
pediatric O
LT O
. O

High O
PELD O
and O
Child O
- O
Pugh O
scores O
before O
LT O
and O
high O
post O
- O
operative O
serum O
Tbil O
may O
be O
contributory O
risk O
factors O
for O
TAC B
- O
related O
seizures O
. O

The O
flavonoid B
apigenin B
delays O
forgetting O
of O
passive O
avoidance O
conditioning O
in O
rats O
. O

The O
present O
experiments O
were O
performed O
to O
study O
the O
effect O
of O
the O
flavonoid B
apigenin B
( O
20 O
mg O
/ O
kg O
intraperitoneally O
( O
i O
. O
p O
. O
) O
, O
1 O
h O
before O
acquisition O
) O
, O
on O
24 O
h O
retention O
performance O
and O
forgetting O
of O
a O
step O
- O
through O
passive O
avoidance O
task O
, O
in O
young O
male O
Wistar O
rats O
. O

There O
were O
no O
differences O
between O
saline O
- O
and O
apigenin B
- O
treated O
groups O
in O
the O
24 O
h O
retention O
trial O
. O

Furthermore O
, O
apigenin B
did O
not O
prevent O
the O
amnesia O
induced O
by O
scopolamine B
( O
1mg O
/ O
kg O
, O
i O
. O
p O
. O
, O
30 O
min O
before O
the O
acquisition O
) O
. O

The O
saline O
- O
and O
apigenin B
- O
treated O
rats O
that O
did O
not O
step O
through O
into O
the O
dark O
compartment O
during O
the O
cut O
- O
off O
time O
( O
540 O
s O
) O
were O
retested O
weekly O
for O
up O
to O
eight O
weeks O
. O

In O
the O
saline O
treated O
group O
, O
the O
first O
significant O
decline O
in O
passive O
avoidance O
response O
was O
observed O
at O
four O
weeks O
, O
and O
complete O
memory O
loss O
was O
found O
five O
weeks O
after O
the O
acquisition O
of O
the O
passive O
avoidance O
task O
. O

At O
the O
end O
of O
the O
experimental O
period O
, O
60 O
% O
of O
the O
animals O
treated O
with O
apigenin B
still O
did O
not O
step O
through O
. O

These O
data O
suggest O
that O
1 O
) O
apigenin B
delays O
the O
long O
- O
term O
forgetting O
but O
did O
not O
modulate O
the O
24 O
h O
retention O
of O
fear O
memory O
and O
2 O
) O
the O
obtained O
beneficial O
effect O
of O
apigenin B
on O
the O
passive O
avoidance O
conditioning O
is O
mediated O
by O
mechanisms O
that O
do O
not O
implicate O
its O
action O
on O
the O
muscarinic O
cholinergic O
system O
. O

Histamine B
antagonists O
and O
d B
- I
tubocurarine I
- O
induced O
hypotension O
in O
cardiac O
surgical O
patients O
. O

Hemodynamic O
effects O
and O
histamine B
release O
by O
bolus O
injection O
of O
0 O
. O
35 O
mg O
/ O
kg O
of O
d B
- I
tubocurarine I
were O
studied O
in O
24 O
patients O
. O

H1 O
- O
and O
H2 O
- O
histamine B
antagonists O
or O
placebo O
were O
given O
before O
dosing O
with O
d B
- I
tubocurarine I
in O
a O
randomized O
double O
- O
blind O
fashion O
to O
four O
groups O
: O
group O
1 O
- O
- O
placebo O
; O
group O
2 O
- O
- O
cimetidine B
, O
4 O
mg O
/ O
kg O
, O
plus O
placebo O
; O
group O
3 O
- O
- O
chlorpheniramine B
, O
0 O
. O
1 O
mg O
/ O
kg O
, O
plus O
placebo O
; O
and O
group O
4 O
- O
- O
cimetidine B
plus O
chlorpheniramine B
. O

Histamine B
release O
occurred O
in O
most O
patients O
, O
the O
highest O
level O
2 O
minutes O
after O
d B
- I
tubocurarine I
dosing O
. O

Group O
1 O
had O
a O
moderate O
negative O
correlation O
between O
plasma O
histamine B
change O
and O
systemic O
vascular O
resistance O
( O
r O
= O
0 O
. O
58 O
; O
P O
less O
than O
0 O
. O
05 O
) O
not O
present O
in O
group O
4 O
. O

Prior O
dosing O
with O
antagonists O
partially O
prevented O
the O
fall O
in O
systemic O
vascular O
resistance O
. O

These O
data O
demonstrate O
that O
the O
hemodynamic O
changes O
associated O
with O
d B
- I
tubocurarine I
dosing O
are O
only O
partially O
explained O
by O
histamine B
release O
. O

Thus O
prior O
dosing O
with O
H1 O
- O
and O
H2 O
- O
antagonists O
provides O
only O
partial O
protection O
. O

Cholecystokinin B
- I
octapeptide I
restored O
morphine B
- O
induced O
hippocampal O
long O
- O
term O
potentiation O
impairment O
in O
rats O
. O

Cholecystokinin B
- I
octapeptide I
( O
CCK B
- I
8 I
) O
, O
which O
is O
a O
typical O
brain O
- O
gut O
peptide O
, O
exerts O
a O
wide O
range O
of O
biological O
activities O
on O
the O
central O
nervous O
system O
. O

We O
have O
previously O
reported O
that O
CCK B
- I
8 I
significantly O
alleviated O
morphine B
- O
induced O
amnesia O
and O
reversed O
spine O
density O
decreases O
in O
the O
CA1 O
region O
of O
the O
hippocampus O
in O
morphine B
- O
treated O
animals O
. O

Here O
, O
we O
investigated O
the O
effects O
of O
CCK B
- I
8 I
on O
long O
- O
term O
potentiation O
( O
LTP O
) O
in O
the O
lateral O
perforant O
path O
( O
LPP O
) O
- O
granule O
cell O
synapse O
of O
rat O
dentate O
gyrus O
( O
DG O
) O
in O
acute O
saline O
or O
morphine B
- O
treated O
rats O
. O

Population O
spikes O
( O
PS O
) O
, O
which O
were O
evoked O
by O
stimulation O
of O
the O
LPP O
, O
were O
recorded O
in O
the O
DG O
region O
. O

Acute O
morphine B
( O
30mg O
/ O
kg O
, O
s O
. O
c O
. O
) O
treatment O
significantly O
attenuated O
hippocampal O
LTP O
and O
CCK B
- I
8 I
( O
1ug O
, O
i O
. O
c O
. O
v O
. O
) O
restored O
the O
amplitude O
of O
PS O
that O
was O
attenuated O
by O
morphine B
injection O
. O

Furthermore O
, O
microinjection O
of O
CCK B
- I
8 I
( O
0 O
. O
1 O
and O
1ug O
, O
i O
. O
c O
. O
v O
. O
) O
also O
significantly O
augmented O
hippocampal O
LTP O
in O
saline O
- O
treated O
( O
1ml O
/ O
kg O
, O
s O
. O
c O
. O
) O
rats O
. O

Pre O
- O
treatment O
of O
the O
CCK2 O
receptor O
antagonist O
L B
- I
365 I
, I
260 I
( O
10ug O
, O
i O
. O
c O
. O
v O
) O
reversed O
the O
effects O
of O
CCK B
- I
8 I
, O
but O
the O
CCK1 O
receptor O
antagonist O
L B
- I
364 I
, I
718 I
( O
10ug O
, O
i O
. O
c O
. O
v O
) O
did O
not O
. O

The O
present O
results O
demonstrate O
that O
CCK B
- I
8 I
attenuates O
the O
effect O
of O
morphine B
on O
hippocampal O
LTP O
through O
CCK2 O
receptors O
and O
suggest O
an O
ameliorative O
function O
of O
CCK B
- I
8 I
on O
morphine B
- O
induced O
memory O
impairment O
. O

Glial O
activation O
and O
post O
- O
synaptic O
neurotoxicity O
: O
the O
key O
events O
in O
Streptozotocin B
( O
ICV O
) O
induced O
memory O
impairment O
in O
rats O
. O

In O
the O
present O
study O
the O
role O
of O
glial O
activation O
and O
post O
synaptic O
toxicity O
in O
ICV O
Streptozotocin B
( O
STZ B
) O
induced O
memory O
impaired O
rats O
was O
explored O
. O

In O
experiment O
set O
up O
1 O
: O
Memory O
deficit O
was O
found O
in O
Morris O
water O
maze O
test O
on O
14 O
- O
16 O
days O
after O
STZ B
( O
ICV O
; O
3mg O
/ O
Kg O
) O
administration O
. O

STZ B
causes O
increased O
expression O
of O
GFAP O
, O
CD11b O
and O
TNF O
- O
a O
indicating O
glial O
activation O
and O
neuroinflammation O
. O

STZ B
also O
significantly O
increased O
the O
level O
of O
ROS O
, O
nitrite B
, O
Ca B
( O
2 O
+ O
) O
and O
reduced O
the O
mitochondrial O
activity O
in O
synaptosomal O
preparation O
illustrating O
free O
radical O
generation O
and O
excitotoxicity O
. O

Increased O
expression O
and O
activity O
of O
Caspase O
- O
3 O
was O
also O
observed O
in O
STZ B
treated O
rat O
which O
specify O
apoptotic O
cell O
death O
in O
hippocampus O
and O
cortex O
. O

STZ B
treatment O
showed O
decrease O
expression O
of O
post O
synaptic O
markers O
CaMKIIa O
and O
PSD O
- O
95 O
, O
while O
, O
expression O
of O
pre O
synaptic O
markers O
( O
synaptophysin O
and O
SNAP O
- O
25 O
) O
remains O
unaltered O
indicating O
selective O
post O
synaptic O
neurotoxicity O
. O

Oral O
treatment O
with O
Memantine B
( O
10mg O
/ O
kg O
) O
and O
Ibuprofen B
( O
50 O
mg O
/ O
kg O
) O
daily O
for O
13 O
days O
attenuated O
STZ B
induced O
glial O
activation O
, O
apoptotic O
cell O
death O
and O
post O
synaptic O
neurotoxicity O
in O
rat O
brain O
. O

Further O
, O
in O
experiment O
set O
up O
2 O
: O
where O
memory O
function O
was O
not O
affected O
i O
. O
e O
. O
7 O
- O
9 O
days O
after O
STZ B
treatment O
. O

The O
level O
of O
GFAP O
, O
CD11b O
, O
TNF O
- O
a O
, O
ROS O
and O
nitrite B
levels O
were O
increased O
. O

On O
the O
other O
hand O
, O
apoptotic O
marker O
, O
synaptic O
markers O
, O
mitochondrial O
activity O
and O
Ca B
( O
2 O
+ O
) O
levels O
remained O
unaffected O
. O

Collective O
data O
indicates O
that O
neuroinflammatory O
process O
and O
oxidative O
stress O
occurs O
earlier O
to O
apoptosis O
and O
does O
not O
affect O
memory O
function O
. O

Present O
study O
clearly O
suggests O
that O
glial O
activation O
and O
post O
synaptic O
neurotoxicity O
are O
the O
key O
factors O
in O
STZ B
induced O
memory O
impairment O
and O
neuronal O
cell O
death O
. O

Comparison O
of O
effects O
of O
isotonic O
sodium B
chloride I
with O
diltiazem B
in O
prevention O
of O
contrast O
- O
induced O
nephropathy O
. O

INTRODUCTION O
AND O
OBJECTIVE O
: O
Contrast O
- O
induced O
nephropathy O
( O
CIN O
) O
significantly O
increases O
the O
morbidity O
and O
mortality O
of O
patients O
. O

The O
aim O
of O
this O
study O
is O
to O
investigate O
and O
compare O
the O
protective O
effects O
of O
isotonic O
sodium B
chloride I
with O
sodium B
bicarbonate I
infusion O
and O
isotonic O
sodium B
chloride I
infusion O
with O
diltiazem B
, O
a O
calcium B
channel O
blocker O
, O
in O
preventing O
CIN O
. O

MATERIALS O
AND O
METHODS O
: O
Our O
study O
included O
patients O
who O
were O
administered O
30 O
- O
60 O
mL O
of O
iodinated O
contrast O
agent O
for O
percutaneous O
coronary O
angiography O
( O
PCAG O
) O
, O
all O
with O
creatinine B
values O
between O
1 O
. O
1 O
and O
3 O
. O
1 O
mg O
/ O
dL O
. O

Patients O
were O
divided O
into O
three O
groups O
and O
each O
group O
had O
20 O
patients O
. O

The O
first O
group O
of O
patients O
was O
administered O
isotonic O
sodium B
chloride I
; O
the O
second O
group O
was O
administered O
a O
solution O
that O
of O
5 O
% O
dextrose B
and O
sodium B
bicarbonate I
, O
while O
the O
third O
group O
was O
administered O
isotonic O
sodium B
chloride I
before O
and O
after O
the O
contrast O
injection O
. O

The O
third O
group O
received O
an O
additional O
injection O
of O
diltiazem B
the O
day O
before O
and O
first O
2 O
days O
after O
the O
contrast O
injection O
. O

All O
of O
the O
patients O
' O
plasma O
blood B
urea I
nitrogen I
( O
BUN B
) O
and O
creatinine B
levels O
were O
measured O
on O
the O
second O
and O
seventh O
day O
after O
the O
administration O
of O
intravenous O
contrast O
material O
. O

RESULTS O
: O
The O
basal O
creatinine B
levels O
were O
similar O
for O
all O
three O
groups O
( O
p O
> O
0 O
. O
05 O
) O
. O

Among O
a O
total O
of O
60 O
patients O
included O
in O
the O
study O
, O
16 O
patients O
developed O
acute O
renal O
failure O
( O
ARF O
) O
on O
the O
second O
day O
after O
contrast O
material O
was O
injected O
( O
26 O
. O
6 O
% O
) O
. O

The O
number O
of O
patients O
who O
developed O
ARF O
on O
the O
second O
day O
after O
the O
injection O
in O
the O
first O
group O
was O
five O
( O
25 O
% O
) O
, O
in O
the O
second O
group O
was O
six O
( O
30 O
% O
) O
and O
the O
third O
group O
was O
five O
( O
25 O
% O
) O
( O
p O
> O
0 O
. O
05 O
) O
. O

CONCLUSION O
: O
There O
was O
no O
significant O
difference O
between O
isotonic O
sodium B
chloride I
, O
sodium B
bicarbonate I
and O
isotonic O
sodium B
chloride I
with O
diltiazem B
application O
in O
prevention O
of O
CIN O
. O

Neurocognitive O
and O
neuroradiologic O
central O
nervous O
system O
late O
effects O
in O
children O
treated O
on O
Pediatric O
Oncology O
Group O
( O
POG O
) O
P9605 O
( O
standard O
risk O
) O
and O
P9201 O
( O
lesser O
risk O
) O
acute O
lymphoblastic O
leukemia O
protocols O
( O
ACCL0131 O
) O
: O
a O
methotrexate B
consequence O
? O

A O
report O
from O
the O
Children O
' O
s O
Oncology O
Group O
. O

Concerns O
about O
long O
- O
term O
methotrexate B
( O
MTX B
) O
neurotoxicity O
in O
the O
1990s O
led O
to O
modifications O
in O
intrathecal O
( O
IT O
) O
therapy O
, O
leucovorin B
rescue O
, O
and O
frequency O
of O
systemic O
MTX B
administration O
in O
children O
with O
acute O
lymphoblastic O
leukemia O
. O

In O
this O
study O
, O
neurocognitive O
outcomes O
and O
neuroradiologic O
evidence O
of O
leukoencephalopathy O
were O
compared O
in O
children O
treated O
with O
intense O
central O
nervous O
system O
( O
CNS O
) O
- O
directed O
therapy O
( O
P9605 O
) O
versus O
those O
receiving O
fewer O
CNS O
- O
directed O
treatment O
days O
during O
intensive O
consolidation O
( O
P9201 O
) O
. O

A O
total O
of O
66 O
children O
from O
16 O
Pediatric O
Oncology O
Group O
institutions O
with O
" O
standard O
- O
risk O
" O
acute O
lymphoblastic O
leukemia O
, O
1 O
. O
00 O
to O
9 O
. O
99 O
years O
at O
diagnosis O
, O
without O
evidence O
of O
CNS O
leukemia O
at O
diagnosis O
were O
enrolled O
on O
ACCL0131 B
: O
28 O
from O
P9201 O
and O
38 O
from O
P9605 O
. O

Magnetic O
resonance O
imaging O
scans O
and O
standard O
neuropsychological O
tests O
were O
performed O
> O
2 O
. O
6 O
years O
after O
the O
end O
of O
treatment O
. O

Significantly O
more O
P9605 O
patients O
developed O
leukoencephalopathy O
compared O
with O
P9201 O
patients O
( O
68 O
% O
, O
95 O
% O
confidence O
interval O
49 O
% O
- O
83 O
% O
vs O
. O
22 O
% O
, O
95 O
% O
confidence O
interval O
5 O
% O
- O
44 O
% O
; O
P O
= O
0 O
. O
001 O
) O
identified O
as O
late O
as O
7 O
. O
7 O
years O
after O
the O
end O
of O
treatment O
. O

Overall O
, O
40 O
% O
of O
patients O
scored O
< O
85 O
on O
either O
Verbal O
or O
Performance O
IQ O
. O

Children O
on O
both O
studies O
had O
significant O
attention O
problems O
, O
but O
P9605 B
children O
scored O
below O
average O
on O
more O
neurocognitive O
measures O
than O
those O
treated O
on O
P9201 B
( O
82 O
% O
, O
14 O
/ O
17 O
measures O
vs O
. O
24 O
% O
, O
4 O
/ O
17 O
measures O
) O
. O

This O
supports O
ongoing O
concerns O
about O
intensive O
MTX B
exposure O
as O
a O
major O
contributor O
to O
CNS O
late O
effects O
. O

Tranexamic B
acid I
overdosage O
- O
induced O
generalized O
seizure O
in O
renal O
failure O
. O

We O
report O
a O
45 O
- O
year O
- O
old O
lady O
with O
chronic O
kidney O
disease O
stage O
4 O
due O
to O
chronic O
tubulointerstial O
disease O
. O

She O
was O
admitted O
to O
our O
center O
for O
severe O
anemia O
due O
to O
menorrhagia O
and O
deterioration O
of O
renal O
function O
. O

She O
was O
infused O
three O
units O
of O
packed O
cells O
during O
a O
session O
of O
hemodialysis O
. O

Tranexamic B
acid I
( O
TNA B
) O
1 O
g O
8 O
- O
hourly O
was O
administered O
to O
her O
to O
control O
bleeding O
per O
vaginum O
. O

Two O
hours O
after O
the O
sixth O
dose O
of O
TNA B
, O
she O
had O
an O
episode O
of O
generalized O
tonic O
clonic O
convulsions O
. O

TNA B
was O
discontinued O
. O

Investigations O
of O
the O
patient O
revealed O
no O
biochemical O
or O
structural O
central O
nervous O
system O
abnormalities O
that O
could O
have O
provoked O
the O
convulsions O
. O

She O
did O
not O
require O
any O
further O
dialytic O
support O
. O

She O
had O
no O
further O
episodes O
of O
convulsion O
till O
dis O
- O
charge O
and O
during O
the O
two O
months O
of O
follow O
- O
up O
. O

Thus O
, O
the O
precipitating O
cause O
of O
convulsions O
was O
believed O
to O
be O
an O
overdose O
of O
TNA B
. O

Pre O
- O
treatment O
of O
bupivacaine B
- O
induced O
cardiovascular O
depression O
using O
different O
lipid O
formulations O
of O
propofol B
. O

BACKGROUND O
: O
Pre O
- O
treatment O
with O
lipid O
emulsions O
has O
been O
shown O
to O
increase O
lethal O
doses O
of O
bupivacaine B
, O
and O
the O
lipid O
content O
of O
propofol B
may O
alleviate O
bupivacaine B
- O
induced O
cardiotoxicity O
. O

The O
aim O
of O
this O
study O
is O
to O
investigate O
the O
effects O
of O
propofol B
in O
intralipid B
or O
medialipid O
emulsions O
on O
bupivacaine B
- O
induced O
cardiotoxicity O
. O

METHODS O
: O
Rats O
were O
anaesthetised O
with O
ketamine B
and O
were O
given O
0 O
. O
5 O
mg O
/ O
kg O
/ O
min O
propofol B
in O
intralipid O
( O
Group O
P O
) O
, O
propofol B
in O
medialipid O
( O
Group O
L O
) O
, O
or O
saline O
( O
Group O
C O
) O
over O
20 O
min O
. O

Thereafter O
, O
2 O
mg O
/ O
kg O
/ O
min O
bupivacaine B
0 O
. O
5 O
% O
was O
infused O
. O

We O
recorded O
time O
to O
first O
dysrhythmia O
occurrence O
, O
respective O
times O
to O
25 O
% O
and O
50 O
% O
reduction O
of O
the O
heart O
rate O
( O
HR O
) O
and O
mean O
arterial O
pressure O
, O
and O
time O
to O
asystole O
and O
total O
amount O
of O
bupivacaine B
consumption O
. O

Blood O
and O
tissue O
samples O
were O
collected O
following O
asystole O
. O

RESULTS O
: O
The O
time O
to O
first O
dysrhythmia O
occurrence O
, O
time O
to O
25 O
% O
and O
50 O
% O
reductions O
in O
HR O
, O
and O
time O
to O
asystole O
were O
longer O
in O
Group O
P O
than O
the O
other O
groups O
. O

The O
cumulative O
bupivacaine B
dose O
given O
at O
those O
time O
points O
was O
higher O
in O
Group O
P O
. O
Plasma O
bupivacaine B
levels O
were O
significantly O
lower O
in O
Group O
P O
than O
in O
Group O
C O
. O
Bupivacaine B
levels O
in O
the O
brain O
and O
heart O
were O
significantly O
lower O
in O
Group O
P O
and O
Group O
L O
than O
in O
Group O
C O
. O

CONCLUSION O
: O
We O
conclude O
that O
pre O
- O
treatment O
with O
propofol B
in O
intralipid B
, O
compared O
with O
propofol B
in O
medialipid O
or O
saline O
, O
delayed O
the O
onset O
of O
bupivacaine B
- O
induced O
cardiotoxic O
effects O
as O
well O
as O
reduced O
plasma O
bupivacaine B
levels O
. O

Further O
studies O
are O
needed O
to O
explore O
tissue O
bupivacaine B
levels O
of O
propofol B
in O
medialipid O
and O
adapt O
these O
results O
to O
clinical O
practice O
. O

Drug O
- O
Induced O
Acute O
Liver O
Injury O
Within O
12 O
Hours O
After O
Fluvastatin B
Therapy O
. O

Although O
statins B
are O
generally O
well O
- O
tolerated O
drugs O
, O
recent O
cases O
of O
drug O
- O
induced O
liver O
injury O
associated O
with O
their O
use O
have O
been O
reported O
. O

A O
52 O
- O
year O
- O
old O
Chinese O
man O
reported O
with O
liver O
damage O
, O
which O
appeared O
12 O
hours O
after O
beginning O
treatment O
with O
fluvastatin B
. O

Patient O
presented O
with O
complaints O
of O
increasing O
nausea O
, O
anorexia O
, O
and O
upper O
abdominal O
pain O
. O

His O
laboratory O
values O
showed O
elevated O
creatine B
kinase O
and O
transaminases O
. O

Testing O
for O
autoantibodies O
was O
also O
negative O
. O

The O
liver O
biochemistries O
eventually O
normalized O
within O
3 O
weeks O
of O
stopping O
the O
fluvastatin B
. O

Therefore O
, O
when O
prescribing O
statins B
, O
the O
possibility O
of O
hepatic O
damage O
should O
be O
taken O
into O
account O
. O

Fluconazole B
associated O
agranulocytosis O
and O
thrombocytopenia O
. O

CASE O
: O
We O
describe O
a O
second O
case O
of O
fluconazole B
associated O
agranulocytosis O
with O
thrombocytopenia O
and O
recovery O
upon O
discontinuation O
of O
therapy O
. O

The O
patient O
began O
to O
have O
changes O
in O
white O
blood O
cells O
and O
platelets O
within O
48 O
h O
of O
administration O
of O
fluconazole B
and O
began O
to O
recover O
with O
48 O
h O
of O
discontinuation O
. O

This O
case O
highlights O
that O
drug O
- O
induced O
blood O
dyscrasias O
can O
occur O
unexpectedly O
as O
a O
result O
of O
treatment O
with O
a O
commonly O
used O
drug O
thought O
to O
be O
" O
safe O
" O
. O

CONCLUSION O
: O
According O
to O
Naranjo O
' O
s O
algorithm O
the O
likelihood O
that O
our O
patient O
' O
s O
agranulocytosis O
and O
thrombocytopenia O
occurred O
as O
a O
result O
of O
therapy O
with O
fluconazole B
is O
probable O
, O
with O
a O
total O
of O
six O
points O
. O

We O
feel O
that O
the O
weight O
of O
the O
overall O
evidence O
of O
this O
evidence O
is O
strong O
. O

In O
particular O
the O
temporal O
relationship O
of O
bone O
marrow O
suppression O
to O
the O
initiation O
of O
fluconazole B
and O
the O
abatement O
of O
symptoms O
that O
rapidly O
reversed O
immediately O
following O
discontinuation O
. O

Two O
- O
dimensional O
speckle O
tracking O
echocardiography O
combined O
with O
high O
- O
sensitive O
cardiac O
troponin O
T O
in O
early O
detection O
and O
prediction O
of O
cardiotoxicity O
during O
epirubicine B
- O
based O
chemotherapy O
. O

AIMS O
: O
To O
investigate O
whether O
alterations O
of O
myocardial O
strain O
and O
high O
- O
sensitive O
cardiac O
troponin O
T O
( O
cTnT O
) O
could O
predict O
future O
cardiac O
dysfunction O
in O
patients O
after O
epirubicin B
exposure O
. O

METHODS O
: O
Seventy O
- O
five O
patients O
with O
non O
- O
Hodgkin O
lymphoma O
treated O
with O
epirubicin B
were O
studied O
. O

Blood O
collection O
and O
echocardiography O
were O
performed O
at O
baseline O
, O
1 O
day O
after O
the O
third O
cycle O
, O
and O
1 O
day O
after O
completion O
of O
chemotherapy O
. O

Patients O
were O
studied O
using O
echocardiography O
during O
follow O
- O
up O
. O

Global O
longitudinal O
( O
GLS O
) O
, O
circumferential O
( O
GCS O
) O
, O
and O
radial O
strain O
( O
GRS O
) O
were O
calculated O
using O
speckle O
tracking O
echocardiography O
. O

Left O
ventricular O
ejection O
fraction O
was O
analysed O
by O
real O
- O
time O
3D O
echocardiography O
. O

Cardiotoxicity O
was O
defined O
as O
a O
reduction O
of O
the O
LVEF O
of O
> O
5 O
% O
to O
< O
55 O
% O
with O
symptoms O
of O
heart O
failure O
or O
an O
asymptomatic O
reduction O
of O
the O
LVEF O
of O
> O
10 O
% O
to O
< O
55 O
% O
. O

RESULTS O
: O
Fourteen O
patients O
( O
18 O
. O
67 O
% O
) O
developed O
cardiotoxicity O
after O
treatment O
. O

GLS O
( O
- O
18 O
. O
48 O
+ O
1 O
. O
72 O
% O
vs O
. O
- O
15 O
. O
96 O
+ O
1 O
. O
6 O
% O
) O
, O
GCS O
( O
- O
20 O
. O
93 O
+ O
2 O
. O
86 O
% O
vs O
. O
- O
19 O
. O
20 O
+ O
3 O
. O
21 O
% O
) O
, O
and O
GRS O
( O
39 O
. O
23 O
+ O
6 O
. O
44 O
% O
vs O
. O
34 O
. O
98 O
+ O
6 O
. O
2 O
% O
) O
were O
markedly O
reduced O
and O
cTnT O
was O
elevated O
from O
0 O
. O
0010 O
+ O
0 O
. O
0020 O
to O
0 O
. O
0073 O
+ O
0 O
. O
0038 O
ng O
/ O
mL O
( O
P O
all O
< O
0 O
. O
01 O
) O
at O
the O
completion O
of O
chemotherapy O
compared O
with O

baseline O
values O
. O

A O
> O
15 O
. O
9 O
% O
decrease O
in O
GLS O
[ O
sensitivity O
, O
86 O
% O
; O
specificity O
, O
75 O
% O
; O
area O
under O
the O
curve O
( O
AUC O
) O
= O
0 O
. O
815 O
; O
P O
= O
0 O
. O
001 O
] O
and O
a O
> O
0 O
. O
004 O
ng O
/ O
mL O
elevation O
in O
cTnT O
( O
sensitivity O
, O
79 O
% O
; O
specificity O
, O
64 O
% O
; O
AUC O
= O
0 O
. O
757 O
; O
P O
= O
0 O
. O
005 O
) O
from O
baseline O
to O
the O
third O
cycle O
of O
chemotherapy O
predicted O
later O
cardiotoxicity O
. O

The O
decrease O
in O
GLS O
remained O
the O
only O
independent O
predictor O
of O
cardiotoxicity O
( O
P O
= O
0 O
. O
000 O
) O
. O

CONCLUSIONS O
: O
GLS O
combined O
with O
cTnT O
may O
provide O
a O
reliable O
and O
non O
- O
invasive O
method O
to O
predict O
cardiac O
dysfunction O
in O
patients O
receiving O
anthracycline B
- O
based O
chemotherapy O
. O

Prevention O
of O
etomidate B
- O
induced O
myoclonus O
: O
which O
is O
superior O
: O
Fentanyl B
, O
midazolam B
, O
or O
a O
combination O
? O

A O
Retrospective O
comparative O
study O
. O

BACKGROUND O
: O
In O
this O
retrospective O
comparative O
study O
, O
we O
aimed O
to O
compare O
the O
effectiveness O
of O
fentanyl B
, O
midazolam B
, O
and O
a O
combination O
of O
fentanyl B
and O
midazolam B
to O
prevent O
etomidate B
- O
induced O
myoclonus O
. O

MATERIAL O
AND O
METHODS O
: O
This O
study O
was O
performed O
based O
on O
anesthesia O
records O
. O

Depending O
on O
the O
drugs O
that O
would O
be O
given O
before O
the O
induction O
of O
anesthesia O
with O
etomidate B
, O
the O
patients O
were O
separated O
into O
4 O
groups O
: O
no O
pretreatment O
( O
Group O
NP O
) O
, O
fentanyl B
1 O
ug O
. O
kg O
- O
1 O
( O
Group O
F O
) O
, O
midazolam B
0 O
. O
03 O
mg O
. O
kg O
- O
1 O
( O
Group O
M O
) O
, O
and O
midazolam B
0 O
. O
015 O
mg O
. O
kg O
- O
1 O
+ O
fentanyl B
0 O
. O
5 O
ug O
. O
kg O
- O
1 O
( O
Group O
FM O
) O
. O

Patients O
who O
received O
the O
same O
anesthetic O
procedure O
were O
selected O
: O
2 O
minutes O
after O
intravenous O
injections O
of O
the O
pretreatment O
drugs O
, O
anesthesia O
is O
induced O
with O
0 O
. O
3 O
mg O
. O
kg O
- O
1 O
etomidate B
injected O
intravenously O
over O
a O
period O
of O
20 O
- O
30 O
seconds O
. O

Myoclonic O
movements O
are O
evaluated O
, O
which O
were O
observed O
and O
graded O
according O
to O
clinical O
severity O
during O
the O
2 O
minutes O
after O
etomidate B
injection O
. O

The O
severity O
of O
pain O
due O
to O
etomidate B
injection O
, O
mean O
arterial O
pressure O
, O
heart O
rate O
, O
and O
adverse O
effects O
were O
also O
evaluated O
. O

RESULTS O
: O
Study O
results O
showed O
that O
myoclonus O
incidence O
was O
85 O
% O
, O
40 O
% O
, O
70 O
% O
, O
and O
25 O
% O
in O
Group O
NP O
, O
Group O
F O
, O
Group O
M O
, O
and O
Group O
FM O
, O
respectively O
, O
and O
were O
significantly O
lower O
in O
Group O
F O
and O
Group O
FM O
. O

CONCLUSIONS O
: O
We O
conclude O
that O
pretreatment O
with O
fentanyl B
or O
combination O
of O
fentanyl B
and O
midazolam B
was O
effective O
in O
preventing O
etomidate B
- O
induced O
myoclonus O
. O

Convulsant O
effect O
of O
lindane B
and O
regional O
brain O
concentration O
of O
GABA B
and O
dopamine B
. O

Lindane B
( O
gamma B
- I
hexachlorocyclohexane I
) O
is O
an O
organochlorine O
insecticide O
with O
known O
neurotoxic O
effects O
. O

Its O
mechanism O
of O
action O
is O
not O
well O
understood O
although O
it O
has O
been O
proposed O
that O
lindane B
acts O
as O
a O
non O
- O
competitive O
antagonist O
at O
the O
gamma B
- I
aminobutyric I
acid I
( O
GABA B
) O
- O
A O
receptor O
. O

We O
studied O
the O
effect O
of O
lindane B
( O
150 O
mg O
/ O
kg O
) O
on O
the O
GABAergic O
and O
dopaminergic O
systems O
by O
measuring O
the O
concentration O
of O
GABA B
, O
dopamine B
and O
its O
metabolites O
in O
7 O
brain O
areas O
at O
the O
onset O
of O
seizures O
. O

All O
animals O
suffered O
tonic O
convulsions O
at O
18 O
. O
3 O
+ O
/ O
- O
1 O
. O
4 O
min O
after O
lindane B
administration O
. O

The O
concentration O
of O
GABA B
was O
only O
slightly O
but O
significantly O
decreased O
in O
the O
colliculi O
without O
modifications O
in O
the O
other O
areas O
. O

The O
concentration O
of O
dopamine B
was O
increased O
in O
the O
mesencephalon O
and O
that O
of O
its O
metabolite O
DOPAC B
was O
also O
increased O
in O
the O
mesencephalon O
and O
the O
striatum O
. O

Cholestatic O
presentation O
of O
yellow O
phosphorus B
poisoning O
. O

Yellow O
phosphorus B
, O
a O
component O
of O
certain O
pesticide O
pastes O
and O
fireworks O
, O
is O
well O
known O
to O
cause O
hepatotoxicity O
. O

Poisoning O
with O
yellow O
phosphorus B
classically O
manifests O
with O
acute O
hepatitis O
leading O
to O
acute O
liver O
failure O
which O
may O
need O
liver O
transplantation O
. O

We O
present O
a O
case O
of O
yellow O
phosphorus B
poisoning O
in O
which O
a O
patient O
presented O
with O
florid O
clinical O
features O
of O
cholestasis O
highlighting O
the O
fact O
that O
cholestasis O
can O
rarely O
be O
a O
presenting O
feature O
of O
yellow O
phosphorus B
hepatotoxicity O
. O

Vasovagal O
syncope O
and O
severe O
bradycardia O
following O
intranasal O
dexmedetomidine B
for O
pediatric O
procedural O
sedation O
. O

We O
report O
syncope O
and O
bradycardia O
in O
an O
11 O
- O
year O
- O
old O
girl O
following O
administration O
of O
intranasal O
dexmedetomidine B
for O
sedation O
for O
a O
voiding O
cystourethrogram O
. O

Following O
successful O
completion O
of O
VCUG O
and O
a O
60 O
- O
min O
recovery O
period O
, O
the O
patient O
' O
s O
level O
of O
consciousness O
and O
vital O
signs O
returned O
to O
presedation O
levels O
. O

Upon O
leaving O
the O
sedation O
area O
, O
the O
patient O
collapsed O
, O
with O
no O
apparent O
inciting O
event O
. O

The O
patient O
quickly O
regained O
consciousness O
and O
no O
injury O
occurred O
. O

The O
primary O
abnormality O
found O
was O
persistent O
bradycardia O
, O
and O
she O
was O
admitted O
to O
the O
hospital O
for O
telemetric O
observation O
. O

The O
bradycardia O
lasted O
~ O
2 O
h O
, O
and O
further O
cardiac O
workup O
revealed O
no O
underlying O
abnormality O
. O

Unanticipated O
and O
previously O
unreported O
outcomes O
may O
be O
witnessed O
as O
we O
expand O
the O
use O
of O
certain O
sedatives O
to O
alternative O
routes O
of O
administration O
. O

Paradoxical O
severe O
agitation O
induced O
by O
add O
- O
on O
high O
- O
doses O
quetiapine B
in O
schizo O
- O
affective O
disorder O
. O

We O
report O
the O
case O
of O
a O
35 O
- O
year O
- O
old O
patient O
suffering O
from O
schizo O
- O
affective O
disorder O
since O
the O
age O
of O
19 O
years O
, O
treated O
by O
a O
combination O
of O
first O
- O
generation O
antipsychotics O
, O
zuclopenthixol B
( O
100 O
mg O
/ O
day O
) O
and O
lithium B
( O
1200 O
mg O
/ O
day O
) O
( O
serum O
lithium B
= O
0 O
. O
85 O
mEq O
/ O
l O
) O
. O

This O
patient O
had O
no O
associated O
personality O
disorder O
( O
particularly O
no O
antisocial O
disorder O
) O
and O
no O
substance O
abuse O
disorder O
. O

Within O
the O
48 O
h O
following O
the O
gradual O
introduction O
of O
quetiapine B
( O
up O
to O
600 O
mg O
/ O
day O
) O
, O
the O
patient O
presented O
severe O
agitation O
without O
an O
environmental O
explanation O
, O
contrasting O
with O
the O
absence O
of O
a O
history O
of O
aggressiveness O
or O
personality O
disorder O
. O

The O
diagnoses O
of O
manic O
shift O
and O
akathisia O
were O
dismissed O
. O

The O
withdrawal O
and O
the O
gradual O
reintroduction O
of O
quetiapine B
2 O
weeks O
later O
, O
which O
led O
to O
another O
severe O
agitation O
, O
enabled O
us O
to O
attribute O
the O
agitation O
specifically O
to O
quetiapine B
. O

Antioxidant O
effects O
of O
bovine O
lactoferrin O
on O
dexamethasone B
- O
induced O
hypertension O
in O
rat O
. O

Dexamethasone B
- O
( O
Dex B
- O
) O
induced O
hypertension O
is O
associated O
with O
enhanced O
oxidative O
stress O
. O

Lactoferrin O
( O
LF O
) O
is O
an O
iron B
- O
binding O
glycoprotein O
with O
antihypertensive O
properties O
. O

In O
this O
study O
, O
we O
investigated O
the O
effect O
of O
chronic O
administration O
of O
LF O
on O
oxidative O
stress O
and O
hypertension O
upon O
Dex B
administration O
. O

Male O
Wistar O
rats O
were O
treated O
by O
Dex B
( O
30 O
u O
g O
/ O
kg O
/ O
day O
subcutaneously O
) O
or O
saline O
for O
14 O
days O
. O

Oral O
bovine O
LF O
( O
30 O
, O
100 O
, O
300 O
mg O
/ O
kg O
) O
was O
given O
from O
day O
8 O
to O
14 O
in O
a O
reversal O
study O
. O

In O
a O
prevention O
study O
, O
rats O
received O
4 O
days O
of O
LF B
treatment O
followed O
by O
Dex B
and O
continued O
during O
the O
test O
period O
. O

Systolic O
blood O
pressure O
( O
SBP O
) O
was O
measured O
using O
tail O
- O
cuff O
method O
. O

Thymus O
weight O
was O
used O
as O
a O
marker O
of O
glucocorticoid O
activity O
. O

Plasma O
hydrogen B
peroxide I
( O
H2O2 B
) O
concentration O
and O
ferric B
reducing O
antioxidant O
power O
( O
FRAP O
) O
value O
were O
determined O
. O

Dexamethasone B
significantly O
increased O
SBP O
and O
plasma O
H2O2 B
level O
and O
decreased O
thymus O
and O
body O
weights O
. O

LF O
lowered O
( O
P O
< O
0 O
. O
01 O
) O
and O
dose O
dependently O
prevented O
( O
P O
< O
0 O
. O
001 O
) O
Dex B
- O
induced O
hypertension O
. O

LF O
prevented O
body O
weight O
loss O
and O
significantly O
reduced O
the O
elevated O
plasma O
H2O2 B
and O
increased O
FRAP O
values O
. O

Chronic O
administration O
of O
LF O
strongly O
reduced O
the O
blood O
pressure O
and O
production O
of O
ROS O
and O
improved O
antioxidant O
capacity O
in O
Dex B
- O
induced O
hypertension O
, O
suggesting O
the O
role O
of O
inhibition O
of O
oxidative O
stress O
as O
another O
mechanism O
of O
antihypertensive O
action O
of O
LF O
. O

The O
association O
between O
tranexamic B
acid I
and O
convulsive O
seizures O
after O
cardiac O
surgery O
: O
a O
multivariate O
analysis O
in O
11 O
529 O
patients O
. O

Because O
of O
a O
lack O
of O
contemporary O
data O
regarding O
seizures O
after O
cardiac O
surgery O
, O
we O
undertook O
a O
retrospective O
analysis O
of O
prospectively O
collected O
data O
from O
11 O
529 O
patients O
in O
whom O
cardiopulmonary O
bypass O
was O
used O
from O
January O
2004 O
to O
December O
2010 O
. O

A O
convulsive O
seizure O
was O
defined O
as O
a O
transient O
episode O
of O
disturbed O
brain O
function O
characterised O
by O
abnormal O
involuntary O
motor O
movements O
. O

Multivariate O
regression O
analysis O
was O
performed O
to O
identify O
independent O
predictors O
of O
postoperative O
seizures O
. O

A O
total O
of O
100 O
( O
0 O
. O
9 O
% O
) O
patients O
developed O
postoperative O
convulsive O
seizures O
. O

Generalised O
and O
focal O
seizures O
were O
identified O
in O
68 O
and O
32 O
patients O
, O
respectively O
. O

The O
median O
( O
IQR O
[ O
range O
] O
) O
time O
after O
surgery O
when O
the O
seizure O
occurred O
was O
7 O
( O
6 O
- O
12 O
[ O
1 O
- O
216 O
] O
) O
h O
and O
8 O
( O
6 O
- O
11 O
[ O
4 O
- O
18 O
] O
) O
h O
, O
respectively O
. O

Epileptiform O
findings O
on O
electroencephalography O
were O
seen O
in O
19 O
patients O
. O

Independent O
predictors O
of O
postoperative O
seizures O
included O
age O
, O
female O
sex O
, O
redo O
cardiac O
surgery O
, O
calcification O
of O
ascending O
aorta O
, O
congestive O
heart O
failure O
, O
deep O
hypothermic O
circulatory O
arrest O
, O
duration O
of O
aortic O
cross O
- O
clamp O
and O
tranexamic B
acid I
. O

When O
tested O
in O
a O
multivariate O
regression O
analysis O
, O
tranexamic B
acid I
was O
a O
strong O
independent O
predictor O
of O
seizures O
( O
OR O
14 O
. O
3 O
, O
95 O
% O
CI O
5 O
. O
5 O
- O
36 O
. O
7 O
; O
p O
< O
0 O
. O
001 O
) O
. O

Patients O
with O
convulsive O
seizures O
had O
2 O
. O
5 O
times O
higher O
in O
- O
hospital O
mortality O
rates O
and O
twice O
the O
length O
of O
hospital O
stay O
compared O
with O
patients O
without O
convulsive O
seizures O
. O

Mean O
( O
IQR O
[ O
range O
] O
) O
length O
of O
stay O
in O
the O
intensive O
care O
unit O
was O
115 O
( O
49 O
- O
228 O
[ O
32 O
- O
481 O
] O
) O
h O
in O
patients O
with O
convulsive O
seizures O
compared O
with O
26 O
( O
22 O
- O
69 O
[ O
14 O
- O
1080 O
] O
) O
h O
in O
patients O
without O
seizures O
( O
p O
< O
0 O
. O
001 O
) O
. O

Convulsive O
seizures O
are O
a O
serious O
postoperative O
complication O
after O
cardiac O
surgery O
. O

As O
tranexamic B
acid I
is O
the O
only O
modifiable O
factor O
, O
its O
administration O
, O
particularly O
in O
doses O
exceeding O
80 O
mg O
. O
kg O
( O
- O
1 O
) O
, O
should O
be O
weighed O
against O
the O
risk O
of O
postoperative O
seizures O
. O

Dysfunctional O
overnight O
memory O
consolidation O
in O
ecstasy B
users O
. O

Sleep O
plays O
an O
important O
role O
in O
the O
consolidation O
and O
integration O
of O
memory O
in O
a O
process O
called O
overnight O
memory O
consolidation O
. O

Previous O
studies O
indicate O
that O
ecstasy B
users O
have O
marked O
and O
persistent O
neurocognitive O
and O
sleep O
- O
related O
impairments O
. O

We O
extend O
past O
research O
by O
examining O
overnight O
memory O
consolidation O
among O
regular O
ecstasy B
users O
( O
n O
= O
12 O
) O
and O
drug O
naive O
healthy O
controls O
( O
n O
= O
26 O
) O
. O

Memory O
recall O
of O
word O
pairs O
was O
evaluated O
before O
and O
after O
a O
period O
of O
sleep O
, O
with O
and O
without O
interference O
prior O
to O
testing O
. O

In O
addition O
, O
we O
assessed O
neurocognitive O
performances O
across O
tasks O
of O
learning O
, O
memory O
and O
executive O
functioning O
. O

Ecstasy B
users O
demonstrated O
impaired O
overnight O
memory O
consolidation O
, O
a O
finding O
that O
was O
more O
pronounced O
following O
associative O
interference O
. O

Additionally O
, O
ecstasy B
users O
demonstrated O
impairments O
on O
tasks O
recruiting O
frontostriatal O
and O
hippocampal O
neural O
circuitry O
, O
in O
the O
domains O
of O
proactive O
interference O
memory O
, O
long O
- O
term O
memory O
, O
encoding O
, O
working O
memory O
and O
complex O
planning O
. O

We O
suggest O
that O
ecstasy B
- O
associated O
dysfunction O
in O
fronto O
- O
temporal O
circuitry O
may O
underlie O
overnight O
consolidation O
memory O
impairments O
in O
regular O
ecstasy B
users O
. O

Normoammonemic O
encephalopathy O
: O
solely O
valproate B
induced O
or O
multiple O
mechanisms O
? O

A O
77 O
- O
year O
- O
old O
woman O
presented O
with O
subacute O
onset O
progressive O
confusion O
, O
aggression O
, O
auditory O
hallucinations O
and O
delusions O
. O

In O
the O
preceding O
months O
, O
the O
patient O
had O
a O
number O
of O
admissions O
with O
transient O
unilateral O
hemiparesis O
with O
facial O
droop O
, O
and O
had O
been O
started O
on O
valproate B
for O
presumed O
hemiplegic O
migraine O
. O

Valproate B
was O
withdrawn O
soon O
after O
admission O
and O
her O
cognitive O
abilities O
have O
gradually O
improved O
over O
3 O
months O
of O
follow O
- O
up O
. O

Valproate B
levels O
taken O
prior O
to O
withdrawal O
were O
subtherapeutic O
and O
the O
patient O
was O
normoammonaemic O
. O

EEG O
undertaken O
during O
inpatient O
stay O
showed O
changes O
consistent O
with O
encephalopathy O
, O
and O
low O
titre O
N B
- I
methyl I
- I
D I
- I
aspartate I
( O
NMDA B
) O
receptor O
antibodies O
were O
present O
in O
this O
patient O
. O

The O
possible O
aetiologies O
of O
valproate B
- O
induced O
encephalopathy O
and O
NMDA B
receptor O
- O
associated O
encephalitis O
present O
a O
diagnostic O
dilemma O
. O

We O
present O
a O
putative O
combinatorial O
hypothesis O
to O
explain O
this O
patient O
' O
s O
symptoms O
. O

Cerebellar O
and O
oculomotor O
dysfunction O
induced O
by O
rapid O
infusion O
of O
pethidine B
. O

Pethidine B
is O
an O
opioid O
that O
gains O
its O
popularity O
for O
the O
effective O
pain O
control O
through O
acting O
on O
the O
opioid O
- O
receptors O
. O

However O
, O
rapid O
pain O
relief O
sometimes O
brings O
about O
unfavourable O
side O
effects O
that O
largely O
limit O
its O
clinical O
utility O
. O

Common O
side O
effects O
include O
nausea O
, O
vomiting O
and O
hypotension O
. O

In O
patients O
with O
impaired O
renal O
and O
liver O
function O
, O
and O
those O
who O
need O
long O
- O
term O
pain O
control O
, O
pethidine B
may O
cause O
excitatory O
central O
nervous O
system O
( O
CNS O
) O
effects O
through O
its O
neurotoxic O
metabolite O
, O
norpethidine B
, O
resulting O
in O
irritability O
and O
seizure O
attack O
. O

On O
the O
contrary O
, O
though O
not O
clinically O
apparent O
, O
pethidine B
potentially O
causes O
inhibitory O
impacts O
on O
the O
CNS O
and O
impairs O
normal O
cerebellar O
and O
oculomotor O
function O
in O
the O
short O
term O
. O

In O
this O
case O
report O
, O
we O
highlight O
opioid O
' O
s O
inhibitory O
side O
effects O
on O
the O
cerebellar O
structure O
that O
causes O
dysmetria O
, O
dysarthria O
, O
reduced O
smooth O
pursuit O
gain O
and O
decreased O
saccadic O
velocity O
. O

Baboon O
syndrome O
induced O
by O
ketoconazole B
. O

A O
27 O
- O
year O
- O
old O
male O
patient O
presented O
with O
a O
maculopapular O
eruption O
on O
the O
flexural O
areas O
and O
buttocks O
after O
using O
oral O
ketoconazole B
. O

The O
patient O
was O
diagnosed O
with O
drug O
- O
induced O
baboon O
syndrome O
based O
on O
his O
history O
, O
which O
included O
prior O
sensitivity O
to O
topical O
ketoconazole B
, O
a O
physical O
examination O
, O
and O
histopathological O
findings O
. O

Baboon O
syndrome O
is O
a O
drug O
- O
or O
contact O
allergen O
- O
related O
maculopapular O
eruption O
that O
typically O
involves O
the O
flexural O
and O
gluteal O
areas O
. O

To O
the O
best O
of O
our O
knowledge O
, O
this O
is O
the O
first O
reported O
case O
of O
ketoconazole B
- O
induced O
baboon O
syndrome O
in O
the O
English O
literature O
. O

A O
Case O
of O
Sudden O
Cardiac O
Death O
due O
to O
Pilsicainide B
- O
Induced O
Torsades O
de O
Pointes O
. O

An O
84 O
- O
year O
- O
old O
male O
received O
oral O
pilsicainide B
, O
a O
pure O
sodium B
channel O
blocker O
with O
slow O
recovery O
kinetics O
, O
to O
convert O
his O
paroxysmal O
atrial O
fibrillation O
to O
a O
sinus O
rhythm O
; O
the O
patient O
developed O
sudden O
cardiac O
death O
two O
days O
later O
. O

The O
Holter O
electrocardiogram O
, O
which O
was O
worn O
by O
chance O
, O
revealed O
torsade O
de O
pointes O
with O
gradually O
prolonged O
QT O
intervals O
. O

This O
drug O
is O
rapidly O
absorbed O
from O
the O
gastrointestinal O
tract O
, O
and O
most O
of O
it O
is O
excreted O
from O
the O
kidney O
. O

Although O
the O
patient O
' O
s O
renal O
function O
was O
not O
highly O
impaired O
and O
the O
dose O
of O
pilsicainide B
was O
low O
, O
the O
plasma O
concentration O
of O
pilsicainide B
may O
have O
been O
high O
, O
which O
can O
produce O
torsades O
de O
pointes O
in O
the O
octogenarian O
. O

Although O
the O
oral O
administration O
of O
class O
IC O
drugs O
, O
including O
pilsicainide B
, O
is O
effective O
to O
terminate O
atrial O
fibrillation O
, O
careful O
consideration O
must O
be O
taken O
before O
giving O
these O
drugs O
to O
octogenarians O
. O

All B
- I
trans I
retinoic I
acid I
- O
induced O
inflammatory O
myositis O
in O
a O
patient O
with O
acute O
promyelocytic O
leukemia O
. O

All B
- I
trans I
retinoic I
acid I
( O
ATRA B
) O
, O
a O
component O
of O
standard O
therapy O
for O
acute O
promyelocytic O
leukemia O
( O
APL O
) O
, O
is O
associated O
with O
potentially O
serious O
but O
treatable O
adverse O
effects O
involving O
numerous O
organ O
systems O
, O
including O
rare O
skeletal O
muscle O
involvement O
. O

Only O
a O
handful O
of O
cases O
of O
ATRA B
- O
induced O
myositis O
in O
children O
have O
been O
reported O
, O
and O
none O
in O
the O
radiology O
literature O
. O

We O
present O
such O
a O
case O
in O
a O
15 O
- O
year O
- O
old O
boy O
with O
APL O
, O
where O
recognition O
of O
imaging O
findings O
played O
a O
crucial O
role O
in O
making O
the O
diagnosis O
and O
facilitated O
prompt O
, O
effective O
treatment O
. O

Tolerability O
of O
lomustine B
in O
combination O
with O
cyclophosphamide B
in O
dogs O
with O
lymphoma O
. O

This O
retrospective O
study O
describes O
toxicity O
associated O
with O
a O
protocol O
of O
lomustine B
( O
CCNU B
) O
and O
cyclophosphamide B
( O
CTX B
) O
in O
dogs O
with O
lymphoma O
. O

CCNU B
was O
administered O
per O
os O
( O
PO O
) O
at O
a O
targeted O
dosage O
of O
60 O
mg O
/ O
m O
( O
2 O
) O
body O
surface O
area O
on O
day O
0 O
, O
CTX B
was O
administered O
PO O
at O
a O
targeted O
dosage O
of O
250 O
mg O
/ O
m O
( O
2 O
) O
divided O
over O
days O
0 O
through O
4 O
, O
and O
all O
dogs O
received O
prophylactic O
antibiotics O
. O

Ninety O
treatments O
were O
given O
to O
the O
57 O
dogs O
included O
in O
the O
study O
. O

Neutropenia O
was O
the O
principal O
toxic O
effect O
, O
and O
the O
overall O
frequency O
of O
grade O
4 O
neutropenia O
after O
the O
first O
treatment O
of O
CCNU B
/ O
CTX B
was O
30 O
% O
( O
95 O
% O
confidence O
interval O
, O
19 O
- O
43 O
% O
) O
. O

The O
mean O
body O
weight O
of O
dogs O
with O
grade O
4 O
neutropenia O
( O
19 O
. O
7 O
kg O
+ O
13 O
. O
4 O
kg O
) O
was O
significantly O
less O
than O
the O
mean O
body O
weight O
of O
dogs O
that O
did O
not O
develop O
grade O
4 O
neutropenia O
( O
31 O
. O
7 O
kg O
+ O
12 O
. O
4 O
kg O
; O
P O
= O
. O
005 O
) O
. O

One O
dog O
( O
3 O
% O
) O
developed O
hematologic O
changes O
suggestive O
of O
hepatotoxicity O
. O

No O
dogs O
had O
evidence O
of O
either O
renal O
toxicity O
or O
hemorrhagic O
cystitis O
. O

Adverse O
gastrointestinal O
effects O
were O
uncommon O
. O

On O
the O
basis O
of O
the O
findings O
reported O
herein O
, O
a O
dose O
of O
60 O
mg O
/ O
m O
( O
2 O
) O
of O
CCNU B
combined O
with O
250 O
mg O
/ O
m O
( O
2 O
) O
of O
CTX B
( O
divided O
over O
5 O
days O
) O
q O
4 O
wk O
is O
tolerable O
in O
tumor O
- O
bearing O
dogs O
. O

Nelarabine B
neurotoxicity O
with O
concurrent O
intrathecal O
chemotherapy O
: O
Case O
report O
and O
review O
of O
literature O
. O

Severe O
nelarabine B
neurotoxicity O
in O
a O
patient O
who O
received O
concurrent O
intrathecal O
( O
IT O
) O
chemotherapy O
is O
reported O
. O

A O
37 O
- O
year O
- O
old O
Caucasian O
woman O
with O
a O
history O
of O
T O
- O
cell O
lymphoblastic O
lymphoma O
was O
admitted O
for O
relapsed O
disease O
. O

She O
was O
originally O
treated O
with O
induction O
chemotherapy O
followed O
by O
an O
autologous O
transplant O
. O

She O
developed O
relapsed O
disease O
10 O
months O
later O
with O
leukemic O
involvement O
. O

She O
was O
re O
- O
induced O
with O
nelarabine B
1500 O
mg O
/ O
m O
( O
2 O
) O
on O
days O
1 O
, O
3 O
, O
and O
5 O
with O
1 O
dose O
of O
IT O
cytarabine B
100 O
mg O
on O
day O
2 O
as O
central O
nervous O
system O
( O
CNS O
) O
prophylaxis O
. O

At O
the O
time O
of O
treatment O
, O
she O
was O
on O
continuous O
renal O
replacement O
therapy O
due O
to O
sequelae O
of O
tumor O
lysis O
syndrome O
( O
TLS O
) O
. O

She O
tolerated O
therapy O
well O
, O
entered O
a O
complete O
remission O
, O
and O
recovered O
her O
renal O
function O
. O

She O
received O
a O
second O
cycle O
of O
nelarabine B
without O
additional O
IT O
prophylaxis O
one O
month O
later O
. O

A O
week O
after O
this O
second O
cycle O
, O
she O
noted O
numbness O
in O
her O
lower O
extremities O
. O

Predominantly O
sensory O
, O
though O
also O
motor O
and O
autonomic O
, O
peripheral O
neuropathy O
started O
in O
her O
feet O
, O
ascended O
proximally O
to O
the O
mid O
- O
thoracic O
region O
, O
and O
eventually O
included O
her O
distal O
upper O
extremities O
. O

A O
magnetic O
resonance O
imaging O
( O
MRI O
) O
of O
her O
spine O
demonstrated O
changes O
from O
C2 O
to O
C6 O
consistent O
with O
subacute O
combined O
degeneration O
. O

Nelarabine B
was O
felt O
to O
be O
the O
cause O
of O
her O
symptoms O
. O

Her O
neuropathy O
stabilized O
and O
showed O
slight O
improvement O
and O
ultimately O
received O
an O
unrelated O
, O
reduced O
- O
intensity O
allogeneic O
transplant O
while O
in O
complete O
remission O
, O
but O
relapsed O
disease O
10 O
weeks O
later O
. O

She O
is O
currently O
being O
treated O
with O
best O
supportive O
care O
. O

To O
our O
knowledge O
, O
this O
is O
the O
first O
published O
case O
report O
of O
severe O
neurotoxicity O
caused O
by O
nelarabine B
in O
a O
patient O
who O
received O
concurrent O
IT O
chemotherapy O
. O

Valproate B
- O
induced O
hyperammonemic O
encephalopathy O
in O
a O
renal O
transplanted O
patient O
. O

Neurological O
complications O
after O
renal O
transplantation O
constitute O
an O
important O
cause O
of O
morbidity O
and O
mortality O
. O

Their O
differential O
diagnosis O
is O
difficult O
and O
essential O
for O
subsequent O
patient O
' O
s O
management O
. O

Valproate B
- O
induced O
hyperammonemic O
encephalopathy O
is O
an O
uncommon O
but O
serious O
effect O
of O
valproate B
treatment O
. O

Here O
, O
we O
describe O
the O
case O
of O
a O
15 O
- O
year O
- O
old O
girl O
who O
was O
on O
a O
long O
- O
term O
therapy O
with O
valproate B
due O
to O
epilepsy O
and O
revealed O
impaired O
consciousness O
with O
hyperammonemia O
12 O
days O
after O
renal O
transplantation O
. O

After O
withdraw O
of O
valproate B
, O
patients O
' O
symptoms O
resolved O
within O
24 O
h O
. O

Clinicians O
should O
increase O
their O
awareness O
for O
potential O
complication O
of O
valproate B
, O
especially O
in O
transplanted O
patients O
. O

Necrotising O
fasciitis O
after O
bortezomib B
and O
dexamethasone B
- O
containing O
regimen O
in O
an O
elderly O
patient O
of O
Waldenstrom O
macroglobulinaemia O
. O

Bortezomib B
and O
high O
- O
dose O
dexamethasone B
- O
containing O
regimens O
are O
considered O
to O
be O
generally O
tolerable O
with O
few O
severe O
bacterial O
infections O
in O
patients O
with O
B O
- O
cell O
malignancies O
. O

However O
, O
information O
is O
limited O
concerning O
the O
safety O
of O
the O
regimen O
in O
elderly O
patients O
. O

We O
report O
a O
case O
of O
a O
76 O
- O
year O
- O
old O
man O
with O
Waldenstrom O
macroglobulinaemia O
who O
suffered O
necrotising O
fasciitis O
without O
neutropenia O
after O
the O
combination O
treatment O
with O
bortezomib B
, O
high O
- O
dose O
dexamethasone B
and O
rituximab B
. O

Despite O
immediate O
intravenous O
antimicrobial O
therapy O
, O
he O
succumbed O
23 O
h O
after O
the O
onset O
. O

Physicians O
should O
recognise O
the O
possibility O
of O
fatal O
bacterial O
infections O
related O
to O
bortezomib B
plus O
high O
- O
dose O
dexamethasone B
in O
elderly O
patients O
, O
and O
we O
believe O
this O
case O
warrants O
further O
investigation O
. O

An O
integrated O
characterization O
of O
serological O
, O
pathological O
, O
and O
functional O
events O
in O
doxorubicin B
- O
induced O
cardiotoxicity O
. O

Many O
efficacious O
cancer O
treatments O
cause O
significant O
cardiac O
morbidity O
, O
yet O
biomarkers O
or O
functional O
indices O
of O
early O
damage O
, O
which O
would O
allow O
monitoring O
and O
intervention O
, O
are O
lacking O
. O

In O
this O
study O
, O
we O
have O
utilized O
a O
rat O
model O
of O
progressive O
doxorubicin B
( O
DOX B
) O
- O
induced O
cardiomyopathy O
, O
applying O
multiple O
approaches O
, O
including O
cardiac O
magnetic O
resonance O
imaging O
( O
MRI O
) O
, O
to O
provide O
the O
most O
comprehensive O
characterization O
to O
date O
of O
the O
timecourse O
of O
serological O
, O
pathological O
, O
and O
functional O
events O
underlying O
this O
toxicity O
. O

Hannover O
Wistar O
rats O
were O
dosed O
with O
1 O
. O
25 O
mg O
/ O
kg O
DOX B
weekly O
for O
8 O
weeks O
followed O
by O
a O
4 O
week O
off O
- O
dosing O
" O
recovery O
" O
period O
. O

Electron O
microscopy O
of O
the O
myocardium O
revealed O
subcellular O
degeneration O
and O
marked O
mitochondrial O
changes O
after O
a O
single O
dose O
. O

Histopathological O
analysis O
revealed O
progressive O
cardiomyocyte O
degeneration O
, O
hypertrophy O
/ O
cytomegaly O
, O
and O
extensive O
vacuolation O
after O
two O
doses O
. O

Extensive O
replacement O
fibrosis O
( O
quantified O
by O
Sirius O
red O
staining O
) O
developed O
during O
the O
off O
- O
dosing O
period O
. O

Functional O
indices O
assessed O
by O
cardiac O
MRI O
( O
including O
left O
ventricular O
ejection O
fraction O
( O
LVEF O
) O
, O
cardiac O
output O
, O
and O
E O
/ O
A O
ratio O
) O
declined O
progressively O
, O
reaching O
statistical O
significance O
after O
two O
doses O
and O
culminating O
in O
" O
clinical O
" O
LV O
dysfunction O
by O
12 O
weeks O
. O

Significant O
increases O
in O
peak O
myocardial O
contrast O
enhancement O
and O
serological O
cardiac O
troponin O
I O
( O
cTnI O
) O
emerged O
after O
eight O
doses O
, O
importantly O
preceding O
the O
LVEF O
decline O
to O
< O
50 O
% O
. O

Troponin O
I O
levels O
positively O
correlated O
with O
delayed O
and O
peak O
gadolinium B
contrast O
enhancement O
, O
histopathological O
grading O
, O
and O
diastolic O
dysfunction O
. O

In O
summary O
, O
subcellular O
cardiomyocyte O
degeneration O
was O
the O
earliest O
marker O
, O
followed O
by O
progressive O
functional O
decline O
and O
histopathological O
manifestations O
. O

Myocardial O
contrast O
enhancement O
and O
elevations O
in O
cTnI O
occurred O
later O
. O

However O
, O
all O
indices O
predated O
" O
clinical O
" O
LV O
dysfunction O
and O
thus O
warrant O
further O
evaluation O
as O
predictive O
biomarkers O
. O

Intradermal O
glutamate B
and O
capsaicin B
injections O
: O
intra O
- O
and O
interindividual O
variability O
of O
provoked O
hyperalgesia O
and O
allodynia O
. O

Intradermal O
injections O
of O
glutamate B
and O
capsaicin B
are O
attractive O
to O
use O
in O
human O
experimental O
pain O
models O
because O
hyperalgesia O
and O
allodynia O
mimic O
isolated O
aspects O
of O
clinical O
pain O
disorders O
. O

The O
aim O
of O
the O
present O
study O
was O
to O
investigate O
the O
reproducibility O
of O
these O
models O
. O

Twenty O
healthy O
male O
volunteers O
( O
mean O
age O
24 O
years O
; O
range O
18 O
- O
38 O
years O
) O
received O
intradermal O
injections O
of O
glutamate B
and O
capsaicin B
in O
the O
volar O
forearm O
. O

Magnitudes O
of O
secondary O
pinprick O
hyperalgesia O
and O
brush O
- O
evoked O
allodynia O
were O
investigated O
using O
von O
Frey O
filaments O
( O
gauges O
10 O
, O
15 O
, O
60 O
and O
100 O
g O
) O
and O
brush O
strokes O
. O

Areas O
of O
secondary O
hyperalgesia O
and O
allodynia O
were O
quantified O
immediately O
after O
injection O
and O
after O
15 O
, O
30 O
and O
60 O
min O
. O

Two O
identical O
experiments O
separated O
by O
at O
least O
7 O
days O
were O
performed O
. O

Reproducibility O
across O
and O
within O
volunteers O
( O
inter O
- O
and O
intra O
- O
individual O
variation O
, O
respectively O
) O
was O
assessed O
using O
intraclass O
correlation O
coefficient O
( O
ICC O
) O
and O
coefficient O
of O
variation O
( O
CV O
) O
. O

Secondary O
pinprick O
hyperalgesia O
was O
observed O
as O
a O
marked O
increase O
in O
the O
visual O
analogue O
scale O
( O
VAS O
) O
response O
to O
von O
Frey O
gauges O
60 O
and O
100 O
g O
( O
P O
< O
0 O
. O
001 O
) O
after O
glutamate B
injection O
. O

For O
capsaicin B
, O
secondary O
pinprick O
hyperalgesia O
was O
detected O
with O
all O
von O
Frey O
gauges O
( O
P O
< O
0 O
. O
001 O
) O
. O

Glutamate B
evoked O
reproducible O
VAS O
response O
to O
all O
von O
Frey O
gauges O
( O
ICC O
> O
0 O
. O
60 O
) O
and O
brush O
strokes O
( O
ICC O
> O
0 O
. O
83 O
) O
. O

Capsaicin B
injection O
was O
reproducible O
for O
secondary O
hyperalgesia O
( O
ICC O
> O
0 O
. O
70 O
) O
and O
allodynia O
( O
ICC O
> O
0 O
. O
71 O
) O
. O

Intra O
- O
individual O
variability O
was O
generally O
lower O
for O
the O
VAS O
response O
to O
von O
Frey O
and O
brush O
compared O
with O
areas O
of O
secondary O
hyperalgesia O
and O
allodynia O
. O

In O
conclusion O
, O
glutamate B
and O
capsaicin B
yield O
reproducible O
hyperalgesic O
and O
allodynic O
responses O
, O
and O
the O
present O
model O
is O
well O
suited O
for O
basic O
research O
, O
as O
well O
as O
for O
assessing O
the O
modulation O
of O
central O
phenomena O
. O

Ocular O
- O
specific O
ER O
stress O
reduction O
rescues O
glaucoma O
in O
murine O
glucocorticoid O
- O
induced O
glaucoma O
. O

Administration O
of O
glucocorticoids O
induces O
ocular O
hypertension O
in O
some O
patients O
. O

If O
untreated O
, O
these O
patients O
can O
develop O
a O
secondary O
glaucoma O
that O
resembles O
primary O
open O
- O
angle O
glaucoma O
( O
POAG O
) O
. O

The O
underlying O
pathology O
of O
glucocorticoid O
- O
induced O
glaucoma O
is O
not O
fully O
understood O
, O
due O
in O
part O
to O
lack O
of O
an O
appropriate O
animal O
model O
. O

Here O
, O
we O
developed O
a O
murine O
model O
of O
glucocorticoid O
- O
induced O
glaucoma O
that O
exhibits O
glaucoma O
features O
that O
are O
observed O
in O
patients O
. O

Treatment O
of O
WT O
mice O
with O
topical O
ocular O
0 O
. O
1 O
% O
dexamethasone B
led O
to O
elevation O
of O
intraocular O
pressure O
( O
IOP O
) O
, O
functional O
and O
structural O
loss O
of O
retinal O
ganglion O
cells O
, O
and O
axonal O
degeneration O
, O
resembling O
glucocorticoid O
- O
induced O
glaucoma O
in O
human O
patients O
. O

Furthermore O
, O
dexamethasone B
- O
induced O
ocular O
hypertension O
was O
associated O
with O
chronic O
ER O
stress O
of O
the O
trabecular O
meshwork O
( O
TM O
) O
. O

Similar O
to O
patients O
, O
withdrawal O
of O
dexamethasone B
treatment O
reduced O
elevated O
IOP O
and O
ER O
stress O
in O
this O
animal O
model O
. O

Dexamethasone B
induced O
the O
transcriptional O
factor O
CHOP O
, O
a O
marker O
for O
chronic O
ER O
stress O
, O
in O
the O
anterior O
segment O
tissues O
, O
and O
Chop O
deletion O
reduced O
ER O
stress O
in O
these O
tissues O
and O
prevented O
dexamethasone B
- O
induced O
ocular O
hypertension O
. O

Furthermore O
, O
reduction O
of O
ER O
stress O
in O
the O
TM O
with O
sodium B
4 I
- I
phenylbutyrate I
prevented O
dexamethasone B
- O
induced O
ocular O
hypertension O
in O
WT O
mice O
. O

Our O
data O
indicate O
that O
ER O
stress O
contributes O
to O
glucocorticoid O
- O
induced O
ocular O
hypertension O
and O
suggest O
that O
reducing O
ER O
stress O
has O
potential O
as O
a O
therapeutic O
strategy O
for O
treating O
glucocorticoid O
- O
induced O
glaucoma O
. O

Effects O
of O
ginsenosides B
on O
opioid O
- O
induced O
hyperalgesia O
in O
mice O
. O

Opioid O
- O
induced O
hyperalgesia O
( O
OIH O
) O
is O
characterized O
by O
nociceptive O
sensitization O
caused O
by O
the O
cessation O
of O
chronic O
opioid O
use O
. O

OIH O
can O
limit O
the O
clinical O
use O
of O
opioid O
analgesics O
and O
complicate O
withdrawal O
from O
opioid O
addiction O
. O

In O
this O
study O
, O
we O
investigated O
the O
effects O
of O
Re B
, O
Rg1 B
, O
and O
Rb1 B
ginsenosides B
, O
the O
bioactive O
components O
of O
ginseng O
, O
on O
OIH O
. O

OIH O
was O
achieved O
in O
mice O
after O
subcutaneous O
administration O
of O
morphine B
for O
7 O
consecutive O
days O
three O
times O
per O
day O
. O

During O
withdrawal O
( O
days O
8 O
and O
9 O
) O
, O
these O
mice O
were O
administered O
Re B
, O
Rg1 B
, O
or O
Rb1 B
intragastrically O
two O
times O
per O
day O
. O

On O
the O
test O
day O
( O
day O
10 O
) O
, O
mice O
were O
subjected O
to O
the O
thermal O
sensitivity O
test O
and O
the O
acetic B
acid I
- O
induced O
writhing O
test O
. O

Re B
( O
300 O
mg O
/ O
kg O
) O
inhibited O
OIH O
in O
both O
the O
thermal O
sensitivity O
test O
and O
the O
acetic B
acid I
- O
induced O
writhing O
test O
. O

However O
, O
the O
Rg1 B
and O
Rb1 B
ginsenosides B
failed O
to O
prevent O
OIH O
in O
either O
test O
. O

Furthermore O
, O
Rg1 B
showed O
a O
tendency O
to O
aggravate O
OIH O
in O
the O
acetic B
acid I
- O
induced O
writhing O
test O
. O

Our O
data O
suggested O
that O
the O
ginsenoside B
Re I
, O
but O
not O
Rg1 B
or O
Rb1 O
, O
may O
contribute O
toward O
reversal O
of O
OIH O
. O

A O
comparison O
of O
severe O
hemodynamic O
disturbances O
between O
dexmedetomidine B
and O
propofol B
for O
sedation O
in O
neurocritical O
care O
patients O
. O

OBJECTIVE O
: O
Dexmedetomidine B
and O
propofol B
are O
commonly O
used O
sedatives O
in O
neurocritical O
care O
as O
they O
allow O
for O
frequent O
neurologic O
examinations O
. O

However O
, O
both O
agents O
are O
associated O
with O
significant O
hemodynamic O
side O
effects O
. O

The O
primary O
objective O
of O
this O
study O
is O
to O
compare O
the O
prevalence O
of O
severe O
hemodynamic O
effects O
in O
neurocritical O
care O
patients O
receiving O
dexmedetomidine B
and O
propofol B
. O

DESIGN O
: O
Multicenter O
, O
retrospective O
, O
propensity O
- O
matched O
cohort O
study O
. O

SETTING O
: O
Neurocritical O
care O
units O
at O
two O
academic O
medical O
centers O
with O
dedicated O
neurocritical O
care O
teams O
and O
board O
- O
certified O
neurointensivists O
. O

PATIENTS O
: O
Neurocritical O
care O
patients O
admitted O
between O
July O
2009 O
and O
September O
2012 O
were O
evaluated O
and O
then O
matched O
1 O
: O
1 O
based O
on O
propensity O
scoring O
of O
baseline O
characteristics O
. O

INTERVENTIONS O
: O
Continuous O
sedation O
with O
dexmedetomidine B
or O
propofol B
. O

MEASUREMENTS O
AND O
MAIN O
RESULTS O
: O
A O
total O
of O
342 O
patients O
( O
105 O
dexmedetomidine B
and O
237 O
propofol B
) O
were O
included O
in O
the O
analysis O
, O
with O
190 O
matched O
( O
95 O
in O
each O
group O
) O
by O
propensity O
score O
. O

The O
primary O
outcome O
of O
this O
study O
was O
a O
composite O
of O
severe O
hypotension O
( O
mean O
arterial O
pressure O
< O
60 O
mm O
Hg O
) O
and O
bradycardia O
( O
heart O
rate O
< O
50 O
beats O
/ O
min O
) O
during O
sedative O
infusion O
. O

No O
difference O
in O
the O
primary O
composite O
outcome O
in O
both O
the O
unmatched O
( O
30 O
% O
vs O
30 O
% O
, O
p O
= O
0 O
. O
94 O
) O
or O
matched O
cohorts O
( O
28 O
% O
vs O
34 O
% O
, O
p O
= O
0 O
. O
35 O
) O
could O
be O
found O
. O

When O
analyzed O
separately O
, O
no O
differences O
could O
be O
found O
in O
the O
prevalence O
of O
severe O
hypotension O
or O
bradycardia O
in O
either O
the O
unmatched O
or O
matched O
cohorts O
. O

CONCLUSIONS O
: O
Severe O
hypotension O
and O
bradycardia O
occur O
at O
similar O
prevalence O
in O
neurocritical O
care O
patients O
who O
receive O
dexmedetomidine B
or O
propofol B
. O

Providers O
should O
similarly O
consider O
the O
likelihood O
of O
hypotension O
or O
bradycardia O
before O
starting O
either O
sedative O
. O

Hydroxytyrosol B
ameliorates O
oxidative O
stress O
and O
mitochondrial O
dysfunction O
in O
doxorubicin B
- O
induced O
cardiotoxicity O
in O
rats O
with O
breast O
cancer O
. O

Oxidative O
stress O
is O
involved O
in O
several O
processes O
including O
cancer O
, O
aging O
and O
cardiovascular O
disease O
, O
and O
has O
been O
shown O
to O
potentiate O
the O
therapeutic O
effect O
of O
drugs O
such O
as O
doxorubicin B
. O

Doxorubicin B
causes O
significant O
cardiotoxicity O
characterized O
by O
marked O
increases O
in O
oxidative O
stress O
and O
mitochondrial O
dysfunction O
. O

Herein O
, O
we O
investigate O
whether O
doxorubicin B
- O
associated O
chronic O
cardiac O
toxicity O
can O
be O
ameliorated O
with O
the O
antioxidant O
hydroxytyrosol B
in O
rats O
with O
breast O
cancer O
. O

Thirty O
- O
six O
rats O
bearing O
breast O
tumors O
induced O
chemically O
were O
divided O
into O
4 O
groups O
: O
control O
, O
hydroxytyrosol B
( O
0 O
. O
5mg O
/ O
kg O
, O
5days O
/ O
week O
) O
, O
doxorubicin B
( O
1mg O
/ O
kg O
/ O
week O
) O
, O
and O
doxorubicin B
plus O
hydroxytyrosol B
. O

Cardiac O
disturbances O
at O
the O
cellular O
and O
mitochondrial O
level O
, O
mitochondrial O
electron O
transport O
chain O
complexes O
I O
- O
IV O
and O
apoptosis O
- O
inducing O
factor O
, O
and O
oxidative O
stress O
markers O
have O
been O
analyzed O
. O

Hydroxytyrosol B
improved O
the O
cardiac O
disturbances O
enhanced O
by O
doxorubicin B
by O
significantly O
reducing O
the O
percentage O
of O
altered O
mitochondria O
and O
oxidative O
damage O
. O

These O
results O
suggest O
that O
hydroxytyrosol B
improve O
the O
mitochondrial O
electron O
transport O
chain O
. O

This O
study O
demonstrates O
that O
hydroxytyrosol B
protect O
rat O
heart O
damage O
provoked O
by O
doxorubicin B
decreasing O
oxidative O
damage O
and O
mitochondrial O
alterations O
. O

Amiodarone B
- O
induced O
myxoedema O
coma O
. O

A O
62 O
- O
year O
- O
old O
man O
was O
found O
to O
have O
bradycardia O
, O
hypothermia O
and O
respiratory O
failure O
3 O
weeks O
after O
initiation O
of O
amiodarone B
therapy O
for O
atrial O
fibrillation O
. O

Thyroid O
- O
stimulating O
hormone O
was O
found O
to O
be O
168 O
uIU O
/ O
mL O
( O
nl O
. O
0 O
. O
3 O
- O
5 O
uIU O
/ O
mL O
) O
and O
free O
thyroxine B
( O
FT4 O
) O
was O
< O
0 O
. O
2 O
ng O
/ O
dL O
( O
nl O
. O
0 O
. O
8 O
- O
1 O
. O
8 O
ng O
/ O
dL O
) O
. O

He O
received O
intravenous O
fluids O
, O
vasopressor O
therapy O
and O
stress O
dose O
steroids B
; O
he O
was O
intubated O
and O
admitted O
to O
the O
intensive O
care O
unit O
. O

He O
received O
500 O
ug O
of O
intravenous O
levothyroxine B
in O
the O
first O
18 O
h O
of O
therapy O
, O
and O
150 O
ug O
intravenous O
daily O
thereafter O
. O

Haemodynamic O
improvement O
, O
along O
with O
complete O
recovery O
of O
mental O
status O
, O
occurred O
after O
48 O
h O
. O

Twelve O
hours O
after O
the O
initiation O
of O
therapy O
, O
FT4 O
was O
0 O
. O
96 O
ng O
/ O
dL O
. O

The O
patient O
was O
maintained O
on O
levothyroxine B
175 I
( O
g O
POorally O
daily O
. O

A O
thyroid O
ultrasound O
showed O
diffuse O
heterogeneity O
. O

The O
24 O
hour O
excretion O
of O
iodine B
was O
3657 O
( O
mcg O
( O
25 O
- O
756 O
( O
mcg O
) O
. O

The O
only O
two O
cases O
of O
amiodarone B
- O
induced O
myxoedema O
coma O
in O
the O
literature O
report O
patient O
death O
despite O
supportive O
therapy O
and O
thyroid O
hormone O
replacement O
. O

This O
case O
represents O
the O
most O
thoroughly O
investigated O
case O
of O
amiodarone B
- O
induced O
myxoedema O
coma O
with O
a O
history O
significant O
for O
subclinical O
thyroid O
disease O
. O

Use O
of O
argatroban B
and O
catheter O
- O
directed O
thrombolysis O
with O
alteplase B
in O
an O
oncology O
patient O
with O
heparin B
- O
induced O
thrombocytopenia O
with O
thrombosis O
. O

PURPOSE O
: O
The O
case O
of O
an O
oncology O
patient O
who O
developed O
heparin B
- O
induced O
thrombocytopenia O
with O
thrombosis O
( O
HITT O
) O
and O
was O
treated O
with O
argatroban B
plus O
catheter O
- O
directed O
thrombolysis O
( O
CDT O
) O
with O
alteplase B
is O
presented O
. O

SUMMARY O
: O
A O
63 O
- O
year O
- O
old O
Caucasian O
man O
with O
renal O
amyloidosis O
undergoing O
peripheral O
blood O
stem O
cell O
collection O
for O
an O
autologous O
stem O
cell O
transplant O
developed O
extensive O
bilateral O
upper O
- O
extremity O
deep O
venous O
thrombosis O
( O
DVT O
) O
and O
pulmonary O
embolism O
secondary O
to O
heparin B
- O
induced O
thrombocytopenia O
. O

A O
continuous O
i O
. O
v O
. O
infusion O
of O
argatroban B
was O
initiated O
, O
and O
the O
patient O
was O
managed O
on O
the O
general O
medical O
floor O
. O

After O
one O
week O
of O
therapy O
, O
he O
was O
transferred O
to O
the O
intensive O
care O
unit O
with O
cardiopulmonary O
compromise O
related O
to O
superior O
vena O
cava O
( O
SVC O
) O
syndrome O
. O

A O
percutaneous O
mechanical O
thrombectomy O
and O
CDT O
with O
alteplase B
were O
attempted O
, O
but O
the O
procedure O
was O
aborted O
due O
to O
epistaxis O
. O

The O
epistaxis O
resolved O
the O
next O
day O
, O
and O
the O
patient O
was O
restarted O
on O
argatroban B
. O

A O
second O
percutaneous O
mechanical O
thrombectomy O
was O
performed O
six O
days O
later O
and O
resulted O
in O
partial O
revascularization O
of O
the O
SVC O
and O
central O
veins O
. O

Postthrombectomy O
continuous O
CDT O
with O
alteplase B
was O
commenced O
while O
argatroban B
was O
withheld O
, O
and O
complete O
patency O
of O
the O
SVC O
and O
central O
veins O
was O
achieved O
after O
three O
days O
of O
therapy O
. O

Alteplase B
was O
discontinued O
, O
and O
the O
patient O
was O
reinitiated O
on O
argatroban B
; O
ultimately O
, O
he O
was O
transitioned O
to O
warfarin B
for O
long O
- O
term O
anticoagulation O
. O

Although O
the O
patient O
recovered O
, O
he O
experienced O
permanent O
vision O
and O
hearing O
loss O
, O
as O
well O
as O
end O
- O
stage O
renal O
disease O
. O

CONCLUSION O
: O
A O
63 O
- O
year O
- O
old O
man O
with O
renal O
amyloidosis O
and O
SVC O
syndrome O
secondary O
to O
HITT O
was O
successfully O
treated O
with O
argatroban B
and O
CDT O
with O
alteplase B
. O

Effects O
of O
dehydroepiandrosterone B
in O
amphetamine B
- O
induced O
schizophrenia O
models O
in O
mice O
. O

OBJECTIVE O
: O
To O
examine O
the O
effects O
of O
dehydroepiandrosterone B
( O
DHEA B
) O
on O
animal O
models O
of O
schizophrenia O
. O

METHODS O
: O
Seventy O
Swiss O
albino O
female O
mice O
( O
25 O
- O
35 O
g O
) O
were O
divided O
into O
4 O
groups O
: O
amphetamine B
- O
free O
( O
control O
) O
, O
amphetamine B
, O
50 O
, O
and O
100 O
mg O
/ O
kg O
DHEA B
. O

The O
DHEA B
was O
administered O
intraperitoneally O
( O
ip O
) O
for O
5 O
days O
. O

Amphetamine B
( O
3 O
mg O
/ O
kg O
ip O
) O
induced O
hyper O
locomotion O
, O
apomorphine B
( O
1 O
. O
5 O
mg O
/ O
kg O
subcutaneously O
[ O
sc O
] O
) O
induced O
climbing O
, O
and O
haloperidol B
( O
1 O
. O
5 O
mg O
/ O
kg O
sc O
) O
induced O
catalepsy O
tests O
were O
used O
as O
animal O
models O
of O
schizophrenia O
. O

The O
study O
was O
conducted O
at O
the O
Animal O
Experiment O
Laboratories O
, O
Department O
of O
Pharmacology O
, O
Medical O
School O
, O
Eskisehir O
Osmangazi O
University O
, O
Eskisehir O
, O
Turkey O
between O
March O
and O
May O
2012 O
. O

Statistical O
analysis O
was O
carried O
out O
using O
Kruskal O
- O
Wallis O
test O
for O
hyper O
locomotion O
, O
and O
one O
- O
way O
ANOVA O
for O
climbing O
and O
catalepsy O
tests O
. O

RESULTS O
: O
In O
the O
amphetamine B
- O
induced O
locomotion O
test O
, O
there O
were O
significant O
increases O
in O
all O
movements O
compared O
with O
the O
amphetamine B
- O
free O
group O
. O

Both O
DHEA B
50 O
mg O
/ O
kg O
( O
p O
< O
0 O
. O
05 O
) O
, O
and O
100 O
mg O
/ O
kg O
( O
p O
< O
0 O
. O
01 O
) O
significantly O
decreased O
all O
movements O
compared O
with O
the O
amphetamine B
- O
induced O
locomotion O
group O
. O

There O
was O
a O
significant O
difference O
between O
groups O
in O
the O
haloperidol B
- O
induced O
catalepsy O
test O
( O
p O
< O
0 O
. O
05 O
) O
. O

There O
was O
no O
significant O
difference O
between O
groups O
in O
terms O
of O
total O
climbing O
time O
in O
the O
apomorphine B
- O
induced O
climbing O
test O
( O
p O
> O
0 O
. O
05 O
) O
. O

CONCLUSION O
: O
We O
observed O
that O
DHEA B
reduced O
locomotor O
activity O
and O
increased O
catalepsy O
at O
both O
doses O
, O
while O
it O
had O
no O
effect O
on O
climbing O
behavior O
. O

We O
suggest O
that O
DHEA B
displays O
typical O
neuroleptic O
- O
like O
effects O
, O
and O
may O
be O
used O
in O
the O
treatment O
of O
schizophrenia O
. O

Availability O
of O
human O
induced O
pluripotent O
stem O
cell O
- O
derived O
cardiomyocytes O
in O
assessment O
of O
drug O
potential O
for O
QT O
prolongation O
. O

Field O
potential O
duration O
( O
FPD O
) O
in O
human O
- O
induced O
pluripotent O
stem O
cell O
- O
derived O
cardiomyocytes O
( O
hiPS O
- O
CMs O
) O
, O
which O
can O
express O
QT O
interval O
in O
an O
electrocardiogram O
, O
is O
reported O
to O
be O
a O
useful O
tool O
to O
predict O
K B
( O
+ O
) O
channel O
and O
Ca B
( O
2 O
+ O
) O
channel O
blocker O
effects O
on O
QT O
interval O
. O

However O
, O
there O
is O
no O
report O
showing O
that O
this O
technique O
can O
be O
used O
to O
predict O
multichannel O
blocker O
potential O
for O
QT O
prolongation O
. O

The O
aim O
of O
this O
study O
is O
to O
show O
that O
FPD O
from O
MEA O
( O
Multielectrode O
array O
) O
of O
hiPS O
- O
CMs O
can O
detect O
QT O
prolongation O
induced O
by O
multichannel O
blockers O
. O

hiPS O
- O
CMs O
were O
seeded O
onto O
MEA O
and O
FPD O
was O
measured O
for O
2min O
every O
10min O
for O
30min O
after O
drug O
exposure O
for O
the O
vehicle O
and O
each O
drug O
concentration O
. O

IKr O
and O
IKs O
blockers O
concentration O
- O
dependently O
prolonged O
corrected O
FPD O
( O
FPDc O
) O
, O
whereas O
Ca B
( O
2 O
+ O
) O
channel O
blockers O
concentration O
- O
dependently O
shortened O
FPDc O
. O

Also O
, O
the O
multichannel O
blockers O
Amiodarone B
, O
Paroxetine B
, O
Terfenadine B
and O
Citalopram B
prolonged O
FPDc B
in O
a O
concentration O
dependent O
manner O
. O

Finally O
, O
the O
IKr O
blockers O
, O
Terfenadine B
and O
Citalopram B
, O
which O
are O
reported O
to O
cause O
Torsade O
de O
Pointes O
( O
TdP O
) O
in O
clinical O
practice O
, O
produced O
early O
afterdepolarization O
( O
EAD O
) O
. O

hiPS O
- O
CMs O
using O
MEA O
system O
and O
FPDc O
can O
predict O
the O
effects O
of O
drug O
candidates O
on O
QT O
interval O
. O

This O
study O
also O
shows O
that O
this O
assay O
can O
help O
detect O
EAD O
for O
drugs O
with O
TdP O
potential O
. O

Dermal O
developmental O
toxicity O
of O
N B
- I
phenylimide I
herbicides O
in O
rats O
. O

BACKGROUND O
: O
S B
- I
53482 I
and O
S B
- I
23121 I
are O
N B
- I
phenylimide I
herbicides O
and O
produced O
embryolethality O
, O
teratogenicity O
( O
mainly O
ventricular O
septal O
defects O
and O
wavy O
ribs O
) O
, O
and O
growth O
retardation O
in O
rats O
in O
conventional O
oral O
developmental O
toxicity O
studies O
. O

Our O
objective O
in O
this O
study O
was O
to O
investigate O
whether O
the O
compounds O
induce O
developmental O
toxicity O
via O
the O
dermal O
route O
, O
which O
is O
more O
relevant O
to O
occupational O
exposure O
, O
hence O
better O
addressing O
human O
health O
risks O
. O

METHODS O
: O
S B
- I
53482 I
was O
administered O
dermally O
to O
rats O
at O
30 O
, O
100 O
, O
and O
300 O
mg O
/ O
kg O
during O
organogenesis O
, O
and O
S B
- I
23121 I
was O
administered O
at O
200 O
, O
400 O
, O
and O
800 O
mg O
/ O
kg O
( O
the O
maximum O
applicable O
dose O
level O
) O
. O

Fetuses O
were O
obtained O
by O
a O
Cesarean O
section O
and O
examined O
for O
external O
, O
visceral O
, O
and O
skeletal O
alterations O
. O

RESULTS O
: O
Dermal O
exposure O
of O
rats O
to O
S B
- I
53482 I
at O
300 O
mg O
/ O
kg O
produced O
patterns O
of O
developmental O
toxicity O
similar O
to O
those O
resulting O
from O
oral O
exposure O
. O

Toxicity O
included O
embryolethality O
, O
teratogenicity O
, O
and O
growth O
retardation O
. O

Dermal O
administration O
of O
S B
- I
23121 I
at O
800 O
mg O
/ O
kg O
resulted O
in O
an O
increased O
incidence O
of O
embryonic O
death O
and O
ventricular O
septal O
defect O
, O
but O
retarded O
fetal O
growth O
was O
not O
observed O
as O
it O
was O
following O
oral O
exposure O
to O
S B
- I
23121 I
. O

CONCLUSIONS O
: O
Based O
on O
the O
results O
, O
S B
- I
53482 I
and O
S B
- I
23121 I
were O
teratogenic O
when O
administered O
dermally O
to O
pregnant O
rats O
as O
were O
the O
compounds O
administered O
orally O
. O

Thus O
, O
investigation O
of O
the O
mechanism O
and O
its O
human O
relevancy O
become O
more O
important O
. O

Rates O
of O
Renal O
Toxicity O
in O
Cancer O
Patients O
Receiving O
Cisplatin B
With O
and O
Without O
Mannitol B
. O

BACKGROUND O
: O
Cisplatin B
is O
a O
widely O
used O
antineoplastic O
. O

One O
of O
the O
major O
complications O
of O
cisplatin B
use O
is O
dose O
- O
limiting O
nephrotoxicity O
. O

There O
are O
many O
strategies O
to O
prevent O
this O
toxicity O
, O
including O
the O
use O
of O
mannitol B
as O
a O
nephroprotectant O
in O
combination O
with O
hydration O
. O

OBJECTIVE O
: O
We O
aimed O
to O
evaluate O
the O
rates O
of O
cisplatin B
- O
induced O
nephrotoxicity O
in O
cancer O
patients O
receiving O
single O
- O
agent O
cisplatin B
with O
and O
without O
mannitol B
. O

METHODS O
: O
This O
single O
- O
center O
retrospective O
analysis O
was O
a O
quasi O
experiment O
created O
by O
the O
national O
mannitol B
shortage O
. O

Data O
were O
collected O
on O
adult O
cancer O
patients O
receiving O
single O
- O
agent O
cisplatin B
as O
an O
outpatient O
from O
January O
2011 O
to O
September O
2012 O
. O

The O
primary O
outcome O
was O
acute O
kidney O
injury O
( O
AKI O
) O
. O

RESULTS O
: O
We O
evaluated O
143 O
patients O
who O
received O
single O
- O
agent O
cisplatin B
; O
97 O
. O
2 O
% O
of O
patients O
had O
head O
and O
neck O
cancer O
as O
their O
primary O
malignancy O
. O

Patients O
who O
did O
not O
receive O
mannitol B
were O
more O
likely O
to O
develop O
nephrotoxicity O
: O
odds O
ratio O
[ O
OR O
] O
= O
2 O
. O
646 O
( O
95 O
% O
CI O
= O
1 O
. O
008 O
, O
6 O
. O
944 O
; O
P O
= O
0 O
. O
048 O
) O
. O

Patients O
who O
received O
the O
100 O
mg O
/ O
m O
( O
2 O
) O
dosing O
and O
patients O
who O
had O
a O
history O
of O
hypertension O
also O
had O
a O
higher O
likelihood O
of O
developing O
nephrotoxicity O
: O
OR O
= O
11 O
. O
494 O
( O
95 O
% O
CI O
= O
4 O
. O
149 O
, O
32 O
. O
258 O
; O
P O
< O
0 O
. O
0001 O
) O
and O
OR O
= O
3 O
. O
219 O
( O
95 O
% O
CI O
= O
1 O
. O
228 O
, O
8 O
. O
439 O
; O
P O
= O
0 O
. O
017 O
) O
, O
respectively O
. O

CONCLUSIONS O
: O
When O
limited O
quantities O
of O
mannitol B
are O
available O
, O
it O
should O
preferentially O
be O
given O
to O
patients O
at O
particularly O
high O
risk O
of O
nephrotoxicity O
. O

Our O
analysis O
suggests O
that O
those O
patients O
receiving O
the O
dosing O
schedule O
of O
100 O
mg O
/ O
m O
( O
2 O
) O
cisplatin B
every O
3 O
weeks O
and O
those O
with O
hypertension O
are O
at O
the O
greatest O
risk O
of O
nephrotoxicity O
and O
would O
benefit O
from O
the O
addition O
of O
mannitol B
. O

Metformin B
protects O
against O
seizures O
, O
learning O
and O
memory O
impairments O
and O
oxidative O
damage O
induced O
by O
pentylenetetrazole B
- O
induced O
kindling O
in O
mice O
. O

Cognitive O
impairment O
, O
the O
most O
common O
and O
severe O
comorbidity O
of O
epilepsy O
, O
greatly O
diminishes O
the O
quality O
of O
life O
. O

However O
, O
current O
therapeutic O
interventions O
for O
epilepsy O
can O
also O
cause O
untoward O
cognitive O
effects O
. O

Thus O
, O
there O
is O
an O
urgent O
need O
for O
new O
kinds O
of O
agents O
targeting O
both O
seizures O
and O
cognition O
deficits O
. O

Oxidative O
stress O
is O
considered O
to O
play O
an O
important O
role O
in O
epileptogenesis O
and O
cognitive O
deficits O
, O
and O
antioxidants O
have O
a O
putative O
antiepileptic O
potential O
. O

Metformin B
, O
the O
most O
commonly O
prescribed O
antidiabetic O
oral O
drug O
, O
has O
antioxidant O
properties O
. O

This O
study O
was O
designed O
to O
evaluate O
the O
ameliorative O
effects O
of O
metformin B
on O
seizures O
, O
cognitive O
impairment O
and O
brain O
oxidative O
stress O
markers O
observed O
in O
pentylenetetrazole B
- O
induced O
kindling O
animals O
. O

Male O
C57BL O
/ O
6 O
mice O
were O
administered O
with O
subconvulsive O
dose O
of O
pentylenetetrazole B
( O
37 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
every O
other O
day O
for O
14 O
injections O
. O

Metformin B
was O
injected O
intraperitoneally O
in O
dose O
of O
200mg O
/ O
kg O
along O
with O
alternate O
- O
day O
PTZ B
. O

We O
found O
that O
metformin B
suppressed O
the O
progression O
of O
kindling O
, O
ameliorated O
the O
cognitive O
impairment O
and O
decreased O
brain O
oxidative O
stress O
. O

Thus O
the O
present O
study O
concluded O
that O
metformin B
may O
be O
a O
potential O
agent O
for O
the O
treatment O
of O
epilepsy O
as O
well O
as O
a O
protective O
medicine O
against O
cognitive O
impairment O
induced O
by O
seizures O
. O

P53 O
inhibition O
exacerbates O
late O
- O
stage O
anthracycline B
cardiotoxicity O
. O

AIMS O
: O
Doxorubicin B
( O
DOX B
) O
is O
an O
effective O
anti O
- O
cancer O
therapeutic O
, O
but O
is O
associated O
with O
both O
acute O
and O
late O
- O
stage O
cardiotoxicity O
. O

Children O
are O
particularly O
sensitive O
to O
DOX B
- O
induced O
heart O
failure O
. O

Here O
, O
the O
impact O
of O
p53 O
inhibition O
on O
acute O
vs O
. O
late O
- O
stage O
DOX B
cardiotoxicity O
was O
examined O
in O
a O
juvenile O
model O
. O

METHODS O
AND O
RESULTS O
: O
Two O
- O
week O
- O
old O
MHC O
- O
CB7 O
mice O
( O
which O
express O
dominant O
- O
interfering O
p53 O
in O
cardiomyocytes O
) O
and O
their O
non O
- O
transgenic O
( O
NON O
- O
TXG O
) O
littermates O
received O
weekly O
DOX B
injections O
for O
5 O
weeks O
( O
25 O
mg O
/ O
kg O
cumulative O
dose O
) O
. O

One O
week O
after O
the O
last O
DOX B
treatment O
( O
acute O
stage O
) O
, O
MHC O
- O
CB7 O
mice O
exhibited O
improved O
cardiac O
function O
and O
lower O
levels O
of O
cardiomyocyte O
apoptosis O
when O
compared O
with O
the O
NON O
- O
TXG O
mice O
. O

Surprisingly O
, O
by O
13 O
weeks O
following O
the O
last O
DOX B
treatment O
( O
late O
stage O
) O
, O
MHC O
- O
CB7 O
exhibited O
a O
progressive O
decrease O
in O
cardiac O
function O
and O
higher O
rates O
of O
cardiomyocyte O
apoptosis O
when O
compared O
with O
NON O
- O
TXG O
mice O
. O

p53 O
inhibition O
blocked O
transient O
DOX B
- O
induced O
STAT3 O
activation O
in O
MHC O
- O
CB7 O
mice O
, O
which O
was O
associated O
with O
enhanced O
induction O
of O
the O
DNA O
repair O
proteins O
Ku70 O
and O
Ku80 O
. O

Mice O
with O
cardiomyocyte O
- O
restricted O
deletion O
of O
STAT3 O
exhibited O
worse O
cardiac O
function O
, O
higher O
levels O
of O
cardiomyocyte O
apoptosis O
, O
and O
a O
greater O
induction O
of O
Ku70 O
and O
Ku80 O
in O
response O
to O
DOX B
treatment O
during O
the O
acute O
stage O
when O
compared O
with O
control O
animals O
. O

CONCLUSION O
: O
These O
data O
support O
a O
model O
wherein O
a O
p53 O
- O
dependent O
cardioprotective O
pathway O
, O
mediated O
via O
STAT3 O
activation O
, O
mitigates O
DOX B
- O
induced O
myocardial O
stress O
during O
drug O
delivery O
. O

Furthermore O
, O
these O
data O
suggest O
an O
explanation O
as O
to O
how O
p53 O
inhibition O
can O
result O
in O
cardioprotection O
during O
drug O
treatment O
and O
, O
paradoxically O
, O
enhanced O
cardiotoxicity O
long O
after O
the O
cessation O
of O
drug O
treatment O
. O

Metronidazole B
- O
induced O
encephalopathy O
: O
an O
uncommon O
scenario O
. O

Metronidazole B
can O
produce O
neurological O
complications O
although O
it O
is O
not O
a O
common O
scenario O
. O

We O
present O
a O
case O
where O
a O
patient O
developed O
features O
of O
encephalopathy O
following O
prolonged O
metronidazole B
intake O
. O

Magnetic O
resonance O
imaging O
( O
MRI O
) O
brain O
showed O
abnormal O
signal O
intensity O
involving O
both O
dentate O
nuclei O
of O
cerebellum O
and O
splenium O
of O
corpus O
callosum O
. O

The O
diagnosis O
of O
metronidazole B
toxicity O
was O
made O
by O
the O
MRI O
findings O
and O
supported O
clinically O
. O

Aconitine B
- O
induced O
Ca2 B
+ O
overload O
causes O
arrhythmia O
and O
triggers O
apoptosis O
through O
p38 O
MAPK O
signaling O
pathway O
in O
rats O
. O

Aconitine B
is O
a O
major O
bioactive O
diterpenoid O
alkaloid O
with O
high O
content O
derived O
from O
herbal O
aconitum O
plants O
. O

Emerging O
evidence O
indicates O
that O
voltage O
- O
dependent O
Na B
( O
+ O
) O
channels O
have O
pivotal O
roles O
in O
the O
cardiotoxicity O
of O
aconitine B
. O

However O
, O
no O
reports O
are O
available O
on O
the O
role O
of O
Ca B
( O
2 O
+ O
) O
in O
aconitine B
poisoning O
. O

In O
this O
study O
, O
we O
explored O
the O
importance O
of O
pathological O
Ca B
( O
2 O
+ O
) O
signaling O
in O
aconitine B
poisoning O
in O
vitro O
and O
in O
vivo O
. O

We O
found O
that O
Ca B
( O
2 O
+ O
) O
overload O
lead O
to O
accelerated O
beating O
rhythm O
in O
adult O
rat O
ventricular O
myocytes O
and O
caused O
arrhythmia O
in O
conscious O
freely O
moving O
rats O
. O

To O
investigate O
effects O
of O
aconitine B
on O
myocardial O
injury O
, O
we O
performed O
cytotoxicity O
assay O
in O
neonatal O
rat O
ventricular O
myocytes O
( O
NRVMs O
) O
, O
as O
well O
as O
measured O
lactate B
dehydrogenase O
level O
in O
the O
culture O
medium O
of O
NRVMs O
and O
activities O
of O
serum O
cardiac O
enzymes O
in O
rats O
. O

The O
results O
showed O
that O
aconitine B
resulted O
in O
myocardial O
injury O
and O
reduced O
NRVMs O
viability O
dose O
- O
dependently O
. O

To O
confirm O
the O
pro O
- O
apoptotic O
effects O
, O
we O
performed O
flow O
cytometric O
detection O
, O
cardiac O
histology O
, O
transmission O
electron O
microscopy O
and O
terminal O
deoxynucleotidyl O
transferase O
- O
mediated O
dUTP O
- O
biotin O
nick O
end O
labeling O
assay O
. O

The O
results O
showed O
that O
aconitine B
stimulated O
apoptosis O
time O
- O
dependently O
. O

The O
expression O
analysis O
of O
Ca B
( O
2 O
+ O
) O
handling O
proteins O
demonstrated O
that O
aconitine B
promoted O
Ca B
( O
2 O
+ O
) O
overload O
through O
the O
expression O
regulation O
of O
Ca B
( O
2 O
+ O
) O
handling O
proteins O
. O

The O
expression O
analysis O
of O
apoptosis O
- O
related O
proteins O
revealed O
that O
pro O
- O
apoptotic O
protein O
expression O
was O
upregulated O
, O
and O
anti O
- O
apoptotic O
protein O
BCL O
- O
2 O
expression O
was O
downregulated O
. O

Furthermore O
, O
increased O
phosphorylation O
of O
MAPK O
family O
members O
, O
especially O
the O
P O
- O
P38 O
/ O
P38 O
ratio O
was O
found O
in O
cardiac O
tissues O
. O

Hence O
, O
our O
results O
suggest O
that O
aconitine B
significantly O
aggravates O
Ca B
( O
2 O
+ O
) O
overload O
and O
causes O
arrhythmia O
and O
finally O
promotes O
apoptotic O
development O
via O
phosphorylation O
of O
P38 O
mitogen O
- O
activated O
protein O
kinase O
. O

Chronic O
treatment O
with O
metformin B
suppresses O
toll O
- O
like O
receptor O
4 O
signaling O
and O
attenuates O
left O
ventricular O
dysfunction O
following O
myocardial O
infarction O
. O

Acute O
treatment O
with O
metformin B
has O
a O
protective O
effect O
in O
myocardial O
infarction O
by O
suppression O
of O
inflammatory O
responses O
due O
to O
activation O
of O
AMP B
- O
activated O
protein O
kinase O
( O
AMPK O
) O
. O

In O
the O
present O
study O
, O
the O
effect O
of O
chronic O
pre O
- O
treatment O
with O
metformin B
on O
cardiac O
dysfunction O
and O
toll O
- O
like O
receptor O
4 O
( O
TLR4 O
) O
activities O
following O
myocardial O
infarction O
and O
their O
relation O
with O
AMPK O
were O
assessed O
. O

Male O
Wistar O
rats O
were O
randomly O
assigned O
to O
one O
of O
5 O
groups O
( O
n O
= O
6 O
) O
: O
normal O
control O
and O
groups O
were O
injected O
isoproterenol B
after O
chronic O
pre O
- O
treatment O
with O
0 O
, O
25 O
, O
50 O
, O
or O
100mg O
/ O
kg O
of O
metformin B
twice O
daily O
for O
14 O
days O
. O

Isoproterenol B
( O
100mg O
/ O
kg O
) O
was O
injected O
subcutaneously O
on O
the O
13th O
and O
14th O
days O
to O
induce O
acute O
myocardial O
infarction O
. O

Isoproterenol B
alone O
decreased O
left O
ventricular O
systolic O
pressure O
and O
myocardial O
contractility O
indexed O
as O
LVdp O
/ O
dtmax O
and O
LVdp O
/ O
dtmin O
. O

The O
left O
ventricular O
dysfunction O
was O
significantly O
lower O
in O
the O
groups O
treated O
with O
25 O
and O
50mg O
/ O
kg O
of O
metformin B
. O

Metfromin B
markedly O
lowered O
isoproterenol B
- O
induced O
elevation O
in O
the O
levels O
of O
TLR4 O
mRNA O
, O
myeloid O
differentiation O
protein O
88 O
( O
MyD88 O
) O
, O
tumor O
necrosis O
factor O
- O
alpha O
( O
TNF O
- O
a O
) O
, O
and O
interleukin O
6 O
( O
IL O
- O
6 O
) O
in O
the O
heart O
tissues O
. O

Similar O
changes O
were O
also O
seen O
in O
the O
serum O
levels O
of O
TNF O
- O
a O
and O
IL O
- O
6 O
. O

However O
, O
the O
lower O
doses O
of O
25 O
and O
50mg O
/ O
kg O
were O
more O
effective O
than O
100mg O
/ O
kg O
. O

Phosphorylated O
AMPKa O
( O
p O
- O
AMPK O
) O
in O
the O
myocardium O
was O
significantly O
elevated O
by O
25mg O
/ O
kg O
of O
metformin B
, O
slightly O
by O
50mg O
/ O
kg O
, O
but O
not O
by O
100mg O
/ O
kg O
. O

Chronic O
pre O
- O
treatment O
with O
metformin B
reduces O
post O
- O
myocardial O
infarction O
cardiac O
dysfunction O
and O
suppresses O
inflammatory O
responses O
, O
possibly O
through O
inhibition O
of O
TLR4 O
activities O
. O

This O
mechanism O
can O
be O
considered O
as O
a O
target O
to O
protect O
infarcted O
myocardium O
. O

Unusual O
complications O
of O
antithyroid O
drug O
therapy O
: O
four O
case O
reports O
and O
review O
of O
literature O
. O

Two O
cases O
of O
propylthiouracil B
- O
associated O
acute O
hepatitis O
, O
one O
case O
of O
fatal O
methimazole B
- O
associated O
hepatocellular O
necrosis O
and O
one O
case O
of O
propylthiouracil B
- O
associated O
lupus O
- O
like O
syndrome O
are O
described O
. O

The O
literature O
related O
to O
antithyroid O
drug O
side O
effects O
and O
the O
mechanisms O
for O
their O
occurrence O
are O
reviewed O
and O
the O
efficacy O
and O
complications O
of O
thyroidectomy O
and O
radioiodine B
compared O
to O
those O
of O
antithyroid O
drugs O
. O

It O
is O
concluded O
that O
in O
most O
circumstances O
131I B
is O
the O
therapy O
of O
choice O
for O
hyperthyroidism O
. O

Neuroleptic O
malignant O
syndrome O
induced O
by O
combination O
therapy O
with O
tetrabenazine B
and O
tiapride B
in O
a O
Japanese O
patient O
with O
Huntington O
' O
s O
disease O
at O
the O
terminal O
stage O
of O
recurrent O
breast O
cancer O
. O

We O
herein O
describe O
the O
case O
of O
an O
81 O
- O
year O
- O
old O
Japanese O
woman O
with O
neuroleptic O
malignant O
syndrome O
that O
occurred O
36 O
days O
after O
the O
initiation O
of O
combination O
therapy O
with O
tiapride B
( O
75 O
mg O
/ O
day O
) O
and O
tetrabenazine B
( O
12 O
. O
5 O
mg O
/ O
day O
) O
for O
Huntington O
' O
s O
disease O
. O

The O
patient O
had O
been O
treated O
with O
tiapride B
or O
tetrabenazine B
alone O
without O
any O
adverse O
effects O
before O
the O
administration O
of O
the O
combination O
therapy O
. O

She O
also O
had O
advanced O
breast O
cancer O
when O
the O
combination O
therapy O
was O
initiated O
. O

To O
the O
best O
of O
our O
knowledge O
, O
the O
occurrence O
of O
neuroleptic O
malignant O
syndrome O
due O
to O
combination O
therapy O
with O
tetrabenazine B
and O
tiapride B
has O
not O
been O
previously O
reported O
. O

Tetrabenazine B
should O
be O
administered O
very O
carefully O
in O
combination O
with O
other O
neuroleptic O
drugs O
, O
particularly O
in O
patients O
with O
a O
worsening O
general O
condition O
. O

A O
metoprolol B
- O
terbinafine B
combination O
induced O
bradycardia O
. O

To O
report O
a O
sinus O
bradycardia O
induced O
by O
metoprolol B
and O
terbinafine B
drug O
- O
drug O
interaction O
and O
its O
management O
. O

A O
63 O
year O
- O
old O
Caucasian O
man O
on O
metoprolol B
200 O
mg O
/ O
day O
for O
stable O
coronary O
artery O
disease O
was O
prescribed O
a O
90 O
- O
day O
course O
of O
oral O
terbinafine B
250 O
mg O
/ O
day O
for O
onychomycosis O
. O

On O
the O
49th O
day O
of O
terbinafine B
therapy O
, O
he O
was O
brought O
to O
the O
emergency O
room O
for O
a O
decrease O
of O
his O
global O
health O
status O
, O
confusion O
and O
falls O
. O

The O
electrocardiogram O
revealed O
a O
37 O
beats O
/ O
min O
sinus O
bradycardia O
. O

A O
score O
of O
7 O
on O
the O
Naranjo O
adverse O
drug O
reaction O
probability O
scale O
indicates O
a O
probable O
relationship O
between O
the O
patient O
' O
s O
sinus O
bradycardia O
and O
the O
drug O
interaction O
between O
metoprolol B
and O
terbinafine B
. O

The O
heart O
rate O
ameliorated O
first O
with O
a O
decrease O
in O
the O
dose O
of O
metoprolol B
. O

It O
was O
subsequently O
changed O
to O
bisoprolol B
and O
the O
heart O
rate O
remained O
normal O
. O

By O
inhibiting O
the O
cytochrome O
P450 O
2D6 O
, O
terbinafine B
had O
decreased O
metoprolol B
' O
s O
clearance O
, O
leading O
in O
metoprolol B
accumulation O
which O
has O
resulted O
in O
clinically O
significant O
sinus O
bradycardia O
. O

Optochiasmatic O
and O
peripheral O
neuropathy O
due O
to O
ethambutol B
overtreatment O
. O

Ethambutol B
is O
known O
to O
cause O
optic O
neuropathy O
and O
, O
more O
rarely O
, O
axonal O
polyneuropathy O
. O

We O
characterize O
the O
clinical O
, O
neurophysiological O
, O
and O
neuroimaging O
findings O
in O
a O
72 O
- O
year O
- O
old O
man O
who O
developed O
visual O
loss O
and O
paresthesias O
after O
11 O
weeks O
of O
exposure O
to O
a O
supratherapeutic O
dose O
of O
ethambutol B
. O

This O
case O
demonstrates O
the O
selective O
vulnerability O
of O
the O
anterior O
visual O
pathways O
and O
peripheral O
nerves O
to O
ethambutol B
toxicity O
. O

Testosterone B
ameliorates O
streptozotocin B
- O
induced O
memory O
impairment O
in O
male O
rats O
. O

AIM O
: O
To O
study O
the O
effects O
of O
testosterone B
on O
streptozotocin B
( O
STZ B
) O
- O
induced O
memory O
impairment O
in O
male O
rats O
. O

METHODS O
: O
Adult O
male O
Wistar O
rats O
were O
intracerebroventricularly O
( O
icv O
) O
infused O
with O
STZ B
( O
750 O
ug O
) O
on O
d O
1 O
and O
d O
3 O
, O
and O
a O
passive O
avoidance O
task O
was O
assessed O
2 O
weeks O
after O
the O
first O
injection O
of O
STZ B
. O

Castration O
surgery O
was O
performed O
in O
another O
group O
of O
rats O
, O
and O
the O
passive O
avoidance O
task O
was O
assessed O
4 O
weeks O
after O
the O
operation O
. O

Testosterone B
( O
1 O
mg O
. O
kg O
( O
- O
1 O
) O
. O
d O
( O
- O
1 O
) O
, O
sc O
) O
, O
the O
androgen O
receptor O
antagonist O
flutamide B
( O
10 O
mg O
. O
kg O
( O
- O
1 O
) O
. O
d O
( O
- O
1 O
) O
, O
ip O
) O
, O
the O
estrogen B
receptor O
antagonist O
tamoxifen B
( O
1 O
mg O
. O
kg O
( O
- O
1 O
) O
. O
d O
( O
- O
1 O
) O
, O
ip O
) O
or O
the O
aromatase O
inhibitor O
letrozole B
( O
4 O
mg O
. O
kg O
( O
- O
1 O
) O
. O
d O
( O
- O
1 O
) O
, O
ip O
) O
were O
administered O
for O
6 O
d O
after O
the O
first O
injection O
of O
STZ B
. O

RESULTS O
: O
STZ B
administration O
and O
castration O
markedly O
decreased O
both O
STL1 O
( O
the O
short O
memory O
) O
and O
STL2 O
( O
the O
long O
memory O
) O
in O
passive O
avoidance O
tests O
. O

Testosterone B
replacement O
almost O
restored O
the O
STL1 O
and O
STL2 O
in O
castrated O
rats O
, O
and O
significantly O
prolonged O
the O
STL1 O
and O
STL2 O
in O
STZ B
- O
treated O
rats O
. O

Administration O
of O
flutamide B
, O
letrozole B
or O
tamoxifen B
significantly O
impaired O
the O
memory O
in O
intact O
rats O
, O
and O
significantly O
attenuated O
the O
testosterone B
replacement O
in O
improving O
STZ B
- O
and O
castration O
- O
induced O
memory O
impairment O
. O

CONCLUSION O
: O
Testosterone B
administration O
ameliorates O
STZ B
- O
and O
castration O
- O
induced O
memory O
impairment O
in O
male O
Wistar O
rats O
. O

Behavioral O
and O
neurochemical O
studies O
in O
mice O
pretreated O
with O
garcinielliptone B
FC I
in O
pilocarpine B
- O
induced O
seizures O
. O

Garcinielliptone B
FC I
( O
GFC B
) O
isolated O
from O
hexanic O
fraction O
seed O
extract O
of O
species O
Platonia O
insignis O
Mart O
. O

It O
is O
widely O
used O
in O
folk O
medicine O
to O
treat O
skin O
diseases O
in O
both O
humans O
and O
animals O
as O
well O
as O
the O
seed O
decoction O
has O
been O
used O
to O
treat O
diarrheas O
and O
inflammatory O
diseases O
. O

However O
, O
there O
is O
no O
research O
on O
GFC B
effects O
in O
the O
central O
nervous O
system O
of O
rodents O
. O

The O
present O
study O
aimed O
to O
evaluate O
the O
GFC B
effects O
at O
doses O
of O
25 O
, O
50 O
or O
75 O
mg O
/ O
kg O
on O
seizure O
parameters O
to O
determine O
their O
anticonvulsant O
activity O
and O
its O
effects O
on O
amino B
acid I
( O
r B
- I
aminobutyric I
acid I
( O
GABA B
) O
, O
glutamine B
, O
aspartate B
and O
glutathione B
) O
levels O
as O
well O
as O
on O
acetylcholinesterase O
( O
AChE O
) O
activity O
in O
mice O
hippocampus O
after O
seizures O
. O

GFC B
produced O
an O
increased O
latency O
to O
first O
seizure O
, O
at O
doses O
25mg O
/ O
kg O
( O
20 O
. O
12 O
+ O
2 O
. O
20 O
min O
) O
, O
50mg O
/ O
kg O
( O
20 O
. O
95 O
+ O
2 O
. O
21 O
min O
) O
or O
75 O
mg O
/ O
kg O
( O
23 O
. O
43 O
+ O
1 O
. O
99 O
min O
) O
when O
compared O
with O
seized O
mice O
. O

In O
addition O
, O
GABA B
content O
of O
mice O
hippocampus O
treated O
with O
GFC75 B
plus O
P400 O
showed O
an O
increase O
of O
46 O
. O
90 O
% O
when O
compared O
with O
seized O
mice O
. O

In O
aspartate B
, O
glutamine B
and O
glutamate B
levels O
detected O
a O
decrease O
of O
5 O
. O
21 O
% O
, O
13 O
. O
55 O
% O
and O
21 O
. O
80 O
% O
, O
respectively O
in O
mice O
hippocampus O
treated O
with O
GFC75 B
plus I
P400 I
when O
compared O
with O
seized O
mice O
. O

Hippocampus O
mice O
treated O
with O
GFC75 B
plus I
P400 O
showed O
an O
increase O
in O
AChE O
activity O
( O
63 O
. O
30 O
% O
) O
when O
compared O
with O
seized O
mice O
. O

The O
results O
indicate O
that O
GFC B
can O
exert O
anticonvulsant O
activity O
and O
reduce O
the O
frequency O
of O
installation O
of O
pilocarpine B
- O
induced O
status O
epilepticus O
, O
as O
demonstrated O
by O
increase O
in O
latency O
to O
first O
seizure O
and O
decrease O
in O
mortality O
rate O
of O
animals O
. O

In O
conclusion O
, O
our O
data O
suggest O
that O
GFC B
may O
influence O
in O
epileptogenesis O
and O
promote O
anticonvulsant O
actions O
in O
pilocarpine B
model O
by O
modulating O
the O
GABA B
and O
glutamate B
contents O
and O
of O
AChE O
activity O
in O
seized O
mice O
hippocampus O
. O

This O
compound O
may O
be O
useful O
to O
produce O
neuronal O
protection O
and O
it O
can O
be O
considered O
as O
an O
anticonvulsant O
agent O
. O

Standard O
operating O
procedures O
for O
antibiotic O
therapy O
and O
the O
occurrence O
of O
acute O
kidney O
injury O
: O
a O
prospective O
, O
clinical O
, O
non O
- O
interventional O
, O
observational O
study O
. O

INTRODUCTION O
: O
Acute O
kidney O
injury O
( O
AKI O
) O
occurs O
in O
7 O
% O
of O
hospitalized O
and O
66 O
% O
of O
Intensive O
Care O
Unit O
( O
ICU O
) O
patients O
. O

It O
increases O
mortality O
, O
hospital O
length O
of O
stay O
, O
and O
costs O
. O

The O
aim O
of O
this O
study O
was O
to O
investigate O
, O
whether O
there O
is O
an O
association O
between O
adherence O
to O
guidelines O
( O
standard O
operating O
procedures O
( O
SOP O
) O
) O
for O
potentially O
nephrotoxic O
antibiotics O
and O
the O
occurrence O
of O
AKI O
. O

METHODS O
: O
This O
study O
was O
carried O
out O
as O
a O
prospective O
, O
clinical O
, O
non O
- O
interventional O
, O
observational O
study O
. O

Data O
collection O
was O
performed O
over O
a O
total O
of O
170 O
days O
in O
three O
ICUs O
at O
Charite O
- O
Universitaetsmedizin O
Berlin O
. O

A O
total O
of O
675 O
patients O
were O
included O
; O
163 O
of O
these O
had O
therapy O
with O
vancomycin B
, O
gentamicin B
, O
or O
tobramycin B
; O
were O
> O
18 O
years O
; O
and O
treated O
in O
the O
ICU O
for O
> O
24 O
hours O
. O

Patients O
with O
an O
adherence O
to O
SOP B
> O
70 O
% O
were O
classified O
into O
the O
high O
adherence O
group O
( O
HAG O
) O
and O
patients O
with O
an O
adherence O
of O
< O
70 O
% O
into O
the O
low O
adherence O
group O
( O
LAG O
) O
. O

AKI O
was O
defined O
according O
to O
RIFLE O
criteria O
. O

Adherence O
to O
SOPs O
was O
evaluated O
by O
retrospective O
expert O
audit O
. O

Development O
of O
AKI O
was O
compared O
between O
groups O
with O
exact O
Chi2 O
- O
test O
and O
multivariate O
logistic O
regression O
analysis O
( O
two O
- O
sided O
P O
< O
0 O
. O
05 O
) O
. O

RESULTS O
: O
LAG O
consisted O
of O
75 O
patients O
( O
46 O
% O
) O
versus O
88 O
HAG O
patients O
( O
54 O
% O
) O
. O

AKI O
occurred O
significantly O
more O
often O
in O
LAG O
with O
36 O
% O
versus O
21 O
% O
in O
HAG O
( O
P O
= O
0 O
. O
035 O
) O
. O

Basic O
characteristics O
were O
comparable O
, O
except O
an O
increased O
rate O
of O
soft O
tissue O
infections O
in O
LAG O
. O

Multivariate O
analysis O
revealed O
an O
odds O
ratio O
of O
2 O
. O
5 O
- O
fold O
for O
LAG O
to O
develop O
AKI O
compared O
with O
HAG O
( O
95 O
% O
confidence O
interval O
1 O
. O
195 O
to O
5 O
. O
124 O
, O
P O
= O
0 O
. O
039 O
) O
. O

CONCLUSION O
: O
Low O
adherence O
to O
SOPs O
for O
potentially O
nephrotoxic O
antibiotics O
was O
associated O
with O
a O
higher O
occurrence O
of O
AKI O
. O

TRIAL O
REGISTRATION O
: O
Current O
Controlled O
Trials O
ISRCTN54598675 O
. O

Registered O
17 O
August O
2007 O
. O

Rhabdomyolysis O
in O
a O
hepatitis O
C O
virus O
infected O
patient O
treated O
with O
telaprevir B
and O
simvastatin B
. O

A O
46 O
- O
year O
old O
man O
with O
a O
chronic O
hepatitis O
C O
virus O
infection O
received O
triple O
therapy O
with O
ribavirin B
, O
pegylated O
interferon I
and O
telaprevir B
. O

The O
patient O
also O
received O
simvastatin B
. O

One O
month O
after O
starting O
the O
antiviral O
therapy O
, O
the O
patient O
was O
admitted O
to O
the O
hospital O
because O
he O
developed O
rhabdomyolysis O
. O

At O
admission O
simvastatin B
and O
all O
antiviral O
drugs O
were O
discontinued O
because O
toxicity O
due O
to O
a O
drug O
- O
drug O
interaction O
was O
suspected O
. O

The O
creatine B
kinase O
peaked O
at O
62 O
, O
246 O
IU O
/ O
L O
and O
the O
patient O
was O
treated O
with O
intravenous O
normal O
saline O
. O

The O
patient O
' O
s O
renal O
function O
remained O
unaffected O
. O

Fourteen O
days O
after O
hospitalization O
, O
creatine B
kinase O
level O
had O
returned O
to O
230 O
IU O
/ O
L O
and O
the O
patient O
was O
discharged O
. O

Telaprevir B
was O
considered O
the O
probable O
causative O
agent O
of O
an O
interaction O
with O
simvastatin B
according O
to O
the O
Drug O
Interaction O
Probability O
Scale O
. O

The O
interaction O
is O
due O
to O
inhibition O
of O
CYP3A4 O
- O
mediated O
simvastatin B
clearance O
. O

Simvastatin B
plasma O
concentration O
increased O
30 O
times O
in O
this O
patient O
and O
statin B
induced O
muscle O
toxicity O
is O
related O
to O
the O
concentration O
of O
the O
statin B
in O
blood O
. O

In O
conclusion O
, O
with O
this O
case O
we O
illustrate O
that O
telaprevir B
as O
well O
as O
statins B
are O
susceptible O
to O
clinical O
relevant O
drug O
- O
drug O
interactions O
. O

Combination O
of O
bortezomib B
, O
thalidomide B
, O
and O
dexamethasone B
( O
VTD B
) O
as O
a O
consolidation O
therapy O
after O
autologous O
stem O
cell O
transplantation O
for O
symptomatic O
multiple O
myeloma O
in O
Japanese O
patients O
. O

Consolidation O
therapy O
for O
patients O
with O
multiple O
myeloma O
( O
MM O
) O
has O
been O
widely O
adopted O
to O
improve O
treatment O
response O
following O
autologous O
stem O
cell O
transplantation O
. O

In O
this O
study O
, O
we O
retrospectively O
analyzed O
the O
safety O
and O
efficacy O
of O
combination O
regimen O
of O
bortezomib B
, O
thalidomide B
, O
and O
dexamethasone B
( O
VTD B
) O
as O
consolidation O
therapy O
in O
24 O
Japanese O
patients O
with O
newly O
diagnosed O
MM O
. O

VTD O
consisted O
of O
bortezomib B
at O
a O
dose O
of O
1 O
. O
3 O
mg O
/ O
m O
( O
2 O
) O
and O
dexamethasone B
at O
a O
dose O
of O
40 O
mg O
/ O
day O
on O
days O
1 O
, O
8 O
, O
15 O
, O
and O
22 O
of O
a O
35 O
- O
day O
cycle O
, O
with O
daily O
oral O
thalidomide B
at O
a O
dose O
of O
100 O
mg O
/ O
day O
. O

Grade O
3 O
- O
4 O
neutropenia O
and O
thrombocytopenia O
were O
documented O
in O
four O
and O
three O
patients O
( O
17 O
and O
13 O
% O
) O
, O
respectively O
, O
but O
drug O
dose O
reduction O
due O
to O
cytopenia O
was O
not O
required O
in O
any O
case O
. O

Peripheral O
neuropathy O
was O
common O
( O
63 O
% O
) O
, O
but O
severe O
grade O
3 O
- O
4 O
peripheral O
neuropathy O
was O
not O
observed O
. O

Very O
good O
partial O
response O
or O
better O
response O
( O
> O
VGPR O
) O
rates O
before O
and O
after O
consolidation O
therapy O
were O
54 O
and O
79 O
% O
, O
respectively O
. O

Patients O
had O
a O
significant O
probability O
of O
improving O
from O
< O
VGPR O
before O
consolidation O
therapy O
to O
> O
VGPR O
after O
consolidation O
therapy O
( O
p O
= O
0 O
. O
041 O
) O
. O

The O
VTD B
regimen I
may O
be O
safe O
and O
effective O
as O
a O
consolidation O
therapy O
in O
the O
treatment O
of O
MM O
in O
Japanese O
population O
. O

Conversion O
to O
sirolimus B
ameliorates O
cyclosporine B
- O
induced O
nephropathy O
in O
the O
rat O
: O
focus O
on O
serum O
, O
urine O
, O
gene O
, O
and O
protein O
renal O
expression O
biomarkers O
. O

Protocols O
of O
conversion O
from O
cyclosporin B
A I
( O
CsA B
) O
to O
sirolimus B
( O
SRL B
) O
have O
been O
widely O
used O
in O
immunotherapy O
after O
transplantation O
to O
prevent O
CsA B
- O
induced O
nephropathy O
, O
but O
the O
molecular O
mechanisms O
underlying O
these O
protocols O
remain O
nuclear O
. O

This O
study O
aimed O
to O
identify O
the O
molecular O
pathways O
and O
putative O
biomarkers O
of O
CsA B
- O
to O
- O
SRL B
conversion O
in O
a O
rat O
model O
. O

Four O
animal O
groups O
( O
n O
= O
6 O
) O
were O
tested O
during O
9 O
weeks O
: O
control O
, O
CsA B
, O
SRL B
, O
and O
conversion O
( O
CsA B
for O
3 O
weeks O
followed O
by O
SRL B
for O
6 O
weeks O
) O
. O

Classical O
and O
emergent O
serum O
, O
urinary O
, O
and O
kidney O
tissue O
( O
gene O
and O
protein O
expression O
) O
markers O
were O
assessed O
. O

Renal O
lesions O
were O
analyzed O
in O
hematoxylin O
and O
eosin O
, O
periodic B
acid I
- O
Schiff O
, O
and O
Masson O
' O
s O
trichrome O
stains O
. O

SRL B
- O
treated O
rats O
presented O
proteinuria O
and O
NGAL B
( O
serum O
and O
urinary O
) O
as O
the O
best O
markers O
of O
renal O
impairment O
. O

Short O
CsA B
treatment O
presented O
slight O
or O
even O
absent O
kidney O
lesions O
and O
TGF O
- O
b O
, O
NF O
- O
kb O
, O
mTOR O
, O
PCNA O
, O
TP53 O
, O
KIM O
- O
1 O
, O
and O
CTGF O
as O
relevant O
gene O
and O
protein O
changes O
. O

Prolonged O
CsA B
exposure O
aggravated O
renal O
damage O
, O
without O
clear O
changes O
on O
the O
traditional O
markers O
, O
but O
with O
changes O
in O
serums O
TGF O
- O
b O
and O
IL O
- O
7 O
, O
TBARs B
clearance O
, O
and O
kidney O
TGF O
- O
b O
and O
mTOR O
. O

Conversion O
to O
SRL B
prevented O
CsA B
- O
induced O
renal O
damage O
evolution O
( O
absent O
/ O
mild O
grade O
lesions O
) O
, O
while O
NGAL B
( O
serum O
versus O
urine O
) O
seems O
to O
be O
a O
feasible O
biomarker O
of O
CsA B
replacement O
to O
SRL B
. O

Kinin O
B2 O
receptor O
deletion O
and O
blockage O
ameliorates O
cisplatin B
- O
induced O
acute O
renal O
injury O
. O

Cisplatin B
treatment O
has O
been O
adopted O
in O
some O
chemotherapies O
; O
however O
, O
this O
drug O
can O
induce O
acute O
kidney O
injury O
due O
its O
ability O
to O
negatively O
affect O
renal O
function O
, O
augment O
serum O
levels O
of O
creatinine B
and O
urea B
, O
increase O
the O
acute O
tubular O
necrosis O
score O
and O
up O
- O
regulate O
cytokines O
( O
e O
. O
g O
. O
, O
IL O
- O
1b O
and O
TNF O
- O
a O
) O
. O

The O
kinin O
B2 O
receptor O
has O
been O
associated O
with O
the O
inflammation O
process O
, O
as O
well O
as O
the O
regulation O
of O
cytokine O
expression O
, O
and O
its O
deletion O
resulted O
in O
an O
improvement O
in O
the O
diabetic O
nephropathy O
status O
. O

To O
examine O
the O
role O
of O
the O
kinin O
B2 O
receptor O
in O
cisplatin B
- O
induced O
acute O
kidney O
injury O
, O
kinin O
B2 O
receptor O
knockout O
mice O
were O
challenged O
with O
cisplatin B
. O

Additionally O
, O
WT O
mice O
were O
treated O
with O
a O
B2 O
receptor O
antagonist O
after O
cisplatin B
administration O
. O

B2 O
receptor O
- O
deficient O
mice O
were O
less O
sensitive O
to O
this O
drug O
than O
the O
WT O
mice O
, O
as O
shown O
by O
reduced O
weight O
loss O
, O
better O
preservation O
of O
kidney O
function O
, O
down O
regulation O
of O
inflammatory O
cytokines O
and O
less O
acute O
tubular O
necrosis O
. O

Moreover O
, O
treatment O
with O
the O
kinin O
B2 O
receptor O
antagonist O
effectively O
reduced O
the O
levels O
of O
serum O
creatinine B
and O
blood O
urea B
after O
cisplatin B
administration O
. O

Thus O
, O
our O
data O
suggest O
that O
the O
kinin O
B2 O
receptor O
is O
involved O
in O
cisplatin B
- O
induced O
acute O
kidney O
injury O
by O
mediating O
the O
necrotic O
process O
and O
the O
expression O
of O
inflammatory O
cytokines O
, O
thus O
resulting O
in O
declined O
renal O
function O
. O

These O
results O
highlight O
the O
kinin O
B2 O
receptor O
antagonist O
treatment O
in O
amelioration O
of O
nephrotoxicity O
induced O
by O
cisplatin B
therapy O
. O

Safety O
and O
efficacy O
of O
fluocinolone B
acetonide I
intravitreal O
implant O
( O
0 O
. O
59 O
mg O
) O
in O
birdshot O
retinochoroidopathy O
. O

PURPOSE O
: O
To O
report O
the O
treatment O
outcomes O
of O
the O
fluocinolone B
acetonide I
intravitreal O
implant O
( O
0 O
. O
59 O
mg O
) O
in O
patients O
with O
birdshot O
retinochoroidopathy O
whose O
disease O
is O
refractory O
or O
intolerant O
to O
conventional O
immunomodulatory O
therapy O
. O

METHODS O
: O
A O
retrospective O
case O
series O
involving O
11 O
birdshot O
retinochoroidopathy O
patients O
( O
11 O
eyes O
) O
. O

Eleven O
patients O
( O
11 O
eyes O
) O
underwent O
surgery O
for O
fluocinolone B
acetonide I
implant O
( O
0 O
. O
59 O
mg O
) O
. O

Treatment O
outcomes O
of O
interest O
were O
noted O
at O
baseline O
, O
before O
fluocinolone B
acetonide I
implant O
, O
and O
then O
at O
6 O
months O
, O
1 O
year O
, O
2 O
years O
, O
3 O
years O
, O
and O
beyond O
3 O
years O
. O

Disease O
activity O
markers O
, O
including O
signs O
of O
ocular O
inflammation O
, O
evidence O
of O
retinal O
vasculitis O
, O
Swedish O
interactive O
threshold O
algorithm O
- O
short O
wavelength O
automated O
perimetry O
Humphrey O
visual O
field O
analysis O
, O
electroretinographic O
parameters O
, O
and O
optical O
coherence O
tomography O
were O
recorded O
. O

Data O
on O
occurrence O
of O
cataract O
and O
raised O
intraocular O
pressure O
were O
collected O
in O
all O
eyes O
. O

RESULTS O
: O
Intraocular O
inflammation O
was O
present O
in O
54 O
. O
5 O
, O
9 O
. O
9 O
, O
11 O
. O
1 O
, O
and O
0 O
% O
of O
patients O
at O
baseline O
, O
6 O
months O
, O
1 O
year O
, O
2 O
years O
, O
3 O
years O
, O
and O
beyond O
3 O
years O
after O
receiving O
the O
implant O
, O
respectively O
. O

Active O
vasculitis O
was O
noted O
in O
36 O
. O
3 O
% O
patients O
at O
baseline O
and O
0 O
% O
at O
3 O
years O
of O
follow O
- O
up O
. O

More O
than O
20 O
% O
( O
47 O
. O
61 O
- O
67 O
. O
2 O
% O
) O
reduction O
in O
central O
retinal O
thickness O
was O
noted O
in O
all O
patients O
with O
cystoid O
macular O
edema O
at O
6 O
months O
, O
1 O
year O
, O
2 O
years O
, O
and O
3 O
years O
postimplant O
. O

At O
baseline O
, O
54 O
. O
5 O
% O
patients O
were O
on O
immunomodulatory O
agents O
. O

This O
percentage O
decreased O
to O
45 O
. O
45 O
, O
44 O
. O
4 O
, O
and O
14 O
. O
28 O
% O
at O
1 O
year O
, O
2 O
years O
, O
and O
3 O
years O
postimplant O
, O
respectively O
. O

Adverse O
events O
included O
increased O
intraocular O
pressure O
( O
54 O
. O
5 O
% O
) O
and O
cataract O
formation O
( O
100 O
% O
) O
. O

CONCLUSION O
: O
The O
data O
suggest O
that O
fluocinolone B
acetonide I
implant O
( O
0 O
. O
59 O
mg O
) O
helps O
to O
control O
inflammation O
in O
otherwise O
treatment O
- O
refractory O
cases O
of O
birdshot O
retinochoroidopathy O
. O

It O
is O
associated O
with O
significant O
side O
effects O
of O
cataract O
and O
ocular O
hypertension O
requiring O
treatment O
. O

Optimal O
precurarizing O
dose O
of O
rocuronium B
to O
decrease O
fasciculation O
and O
myalgia O
following O
succinylcholine B
administration O
. O

BACKGROUND O
: O
Succinylcholine B
commonly O
produces O
frequent O
adverse O
effects O
, O
including O
muscle O
fasciculation O
and O
myalgia O
. O

The O
current O
study O
identified O
the O
optimal O
dose O
of O
rocuronium B
to O
prevent O
succinylcholine B
- O
induced O
fasciculation O
and O
myalgia O
and O
evaluated O
the O
influence O
of O
rocuronium B
on O
the O
speed O
of O
onset O
produced O
by O
succinylcholine B
. O

METHODS O
: O
This O
randomized O
, O
double O
- O
blinded O
study O
was O
conducted O
in O
100 O
patients O
randomly O
allocated O
into O
five O
groups O
of O
20 O
patients O
each O
. O

Patients O
were O
randomized O
to O
receive O
0 O
. O
02 O
, O
0 O
. O
03 O
, O
0 O
. O
04 O
, O
0 O
. O
05 O
and O
0 O
. O
06 O
mg O
/ O
kg O
rocuronium B
as O
a O
precurarizing O
dose O
. O

Neuromuscular O
monitoring O
after O
each O
precurarizing O
dose O
was O
recorded O
from O
the O
adductor O
pollicis O
muscle O
using O
acceleromyography O
with O
train O
- O
of O
- O
four O
stimulation O
of O
the O
ulnar O
nerve O
. O

All O
patients O
received O
succinylcholine B
1 O
. O
5 O
mg O
/ O
kg O
at O
2 O
minutes O
after O
the O
precurarization O
, O
and O
were O
assessed O
the O
incidence O
and O
severity O
of O
fasciculations O
, O
while O
myalgia O
was O
assessed O
at O
24 O
hours O
after O
surgery O
. O

RESULTS O
: O
The O
incidence O
and O
severity O
of O
visible O
muscle O
fasciculation O
was O
significantly O
less O
with O
increasing O
the O
amount O
of O
precurarizing O
dose O
of O
rocuronium B
( O
P O
< O
0 O
. O
001 O
) O
. O

Those O
of O
myalgia O
tend O
to O
decrease O
according O
to O
increasing O
the O
amount O
of O
precurarizing O
dose O
of O
rocuronium B
, O
but O
there O
was O
no O
significance O
( O
P O
= O
0 O
. O
072 O
) O
. O

The O
onset O
time O
of O
succinylcholine B
was O
significantly O
longer O
with O
increasing O
the O
amount O
of O
precurarizing O
dose O
of O
rocuronium B
( O
P O
< O
0 O
. O
001 O
) O
. O

CONCLUSIONS O
: O
Precurarization O
with O
0 O
. O
04 O
mg O
/ O
kg O
rocuronium B
was O
the O
optimal O
dose O
considering O
the O
reduction O
in O
the O
incidence O
and O
severity O
of O
fasciculation O
and O
myalgia O
with O
acceptable O
onset O
time O
, O
and O
the O
safe O
and O
effective O
precurarization O
. O

Absence O
of O
PKC O
- O
alpha O
attenuates O
lithium B
- O
induced O
nephrogenic O
diabetes O
insipidus O
. O

Lithium B
, O
an O
effective O
antipsychotic O
, O
induces O
nephrogenic O
diabetes O
insipidus O
( O
NDI O
) O
in O
40 O
% O
of O
patients O
. O

The O
decreased O
capacity O
to O
concentrate O
urine O
is O
likely O
due O
to O
lithium B
acutely O
disrupting O
the O
cAMP O
pathway O
and O
chronically O
reducing O
urea B
transporter O
( O
UT O
- O
A1 O
) O
and O
water O
channel O
( O
AQP2 O
) O
expression O
in O
the O
inner O
medulla O
. O

Targeting O
an O
alternative O
signaling O
pathway O
, O
such O
as O
PKC O
- O
mediated O
signaling O
, O
may O
be O
an O
effective O
method O
of O
treating O
lithium B
- O
induced O
polyuria O
. O

PKC O
- O
alpha O
null O
mice O
( O
PKCa O
KO O
) O
and O
strain O
- O
matched O
wild O
type O
( O
WT O
) O
controls O
were O
treated O
with O
lithium B
for O
0 O
, O
3 O
or O
5 O
days O
. O

WT O
mice O
had O
increased O
urine O
output O
and O
lowered O
urine O
osmolality O
after O
3 O
and O
5 O
days O
of O
treatment O
whereas O
PKCa O
KO O
mice O
had O
no O
change O
in O
urine O
output O
or O
concentration O
. O

Western O
blot O
analysis O
revealed O
that O
AQP2 O
expression O
in O
medullary O
tissues O
was O
lowered O
after O
3 O
and O
5 O
days O
in O
WT O
mice O
; O
however O
, O
AQP2 O
was O
unchanged O
in O
PKCa O
KO O
. O

Similar O
results O
were O
observed O
with O
UT O
- O
A1 O
expression O
. O

Animals O
were O
also O
treated O
with O
lithium B
for O
6 O
weeks O
. O

Lithium B
- O
treated O
WT O
mice O
had O
19 O
- O
fold O
increased O
urine O
output O
whereas O
treated O
PKCa O
KO O
animals O
had O
a O
4 O
- O
fold O
increase O
in O
output O
. O

AQP2 O
and O
UT O
- O
A1 O
expression O
was O
lowered O
in O
6 O
week O
lithium B
- O
treated O
WT O
animals O
whereas O
in O
treated O
PKCa O
KO O
mice O
, O
AQP2 O
was O
only O
reduced O
by O
2 O
- O
fold O
and O
UT O
- O
A1 O
expression O
was O
unaffected O
. O

Urinary O
sodium B
, O
potassium B
and O
calcium B
were O
elevated O
in O
lithium B
- O
fed O
WT O
but O
not O
in O
lithium B
- O
fed O
PKCa O
KO O
mice O
. O

Our O
data O
show O
that O
ablation O
of O
PKCa O
preserves O
AQP2 O
and O
UT O
- O
A1 O
protein O
expression O
and O
localization O
in O
lithium B
- O
induced O
NDI O
, O
and O
prevents O
the O
development O
of O
the O
severe O
polyuria O
associated O
with O
lithium B
therapy O
. O

Is O
Dysguesia O
Going O
to O
be O
a O
Rare O
or O
a O
Common O
Side O
- O
effect O
of O
Amlodipine B
? O

A O
very O
rare O
side O
- O
effect O
of O
amlodipine B
is O
dysguesia O
. O

A O
review O
of O
the O
literature O
produced O
only O
one O
case O
. O

We O
report O
a O
case O
about O
a O
female O
with O
essential O
hypertension O
on O
drug O
treatment O
with O
amlodipine B
developed O
loss O
of O
taste O
sensation O
. O

Condition O
moderately O
improved O
on O
stoppage O
of O
the O
drug O
for O
25 O
days O
. O

We O
conclude O
that O
amlodipine B
can O
cause O
dysguesia O
. O

Here O
, O
we O
describe O
the O
clinical O
presentation O
and O
review O
the O
relevant O
literature O
on O
amlodipine B
and O
dysguesia O
. O

Rhabdomyolysis O
in O
association O
with O
simvastatin B
and O
dosage O
increment O
in O
clarithromycin B
. O

Clarithromycin B
is O
the O
most O
documented O
cytochrome O
P450 O
3A4 O
( O
CYP3A4 O
) O
inhibitor O
to O
cause O
an O
adverse O
interaction O
with O
simvastatin B
. O

This O
particular O
case O
is O
of O
interest O
as O
rhabdomyolysis O
only O
occurred O
after O
an O
increase O
in O
the O
dose O
of O
clarithromycin B
. O

The O
patient O
developed O
raised O
cardiac O
biomarkers O
without O
any O
obvious O
cardiac O
issues O
, O
a O
phenomenon O
that O
has O
been O
linked O
to O
rhabdomyolysis O
previously O
. O

To O
date O
, O
there O
has O
been O
no O
reported O
effect O
of O
rhabdomyolysis O
on O
the O
structure O
and O
function O
of O
cardiac O
muscle O
. O

Clinicians O
need O
to O
be O
aware O
of O
prescribing O
concomitant O
medications O
that O
increase O
the O
risk O
of O
myopathy O
or O
inhibit O
the O
CYP3A4 O
enzyme O
. O

Our O
case O
suggests O
that O
troponin O
elevation O
could O
be O
associated O
with O
statin B
induced O
rhabdomyolysis O
, O
which O
may O
warrant O
further O
studies O
. O

Characterization O
of O
a O
novel O
BCHE O
" O
silent O
" O
allele O
: O
point O
mutation O
( O
p O
. O
Val204Asp O
) O
causes O
loss O
of O
activity O
and O
prolonged O
apnea O
with O
suxamethonium B
. O

Butyrylcholinesterase O
deficiency O
is O
characterized O
by O
prolonged O
apnea O
after O
the O
use O
of O
muscle O
relaxants O
( O
suxamethonium B
or O
mivacurium B
) O
in O
patients O
who O
have O
mutations O
in O
the O
BCHE O
gene O
. O

Here O
, O
we O
report O
a O
case O
of O
prolonged O
neuromuscular O
block O
after O
administration O
of O
suxamethonium B
leading O
to O
the O
discovery O
of O
a O
novel O
BCHE O
variant O
( O
c O
. O
695T O
> O
A O
, O
p O
. O
Val204Asp O
) O
. O

Inhibition O
studies O
, O
kinetic O
analysis O
and O
molecular O
dynamics O
were O
undertaken O
to O
understand O
how O
this O
mutation O
disrupts O
the O
catalytic O
triad O
and O
determines O
a O
" O
silent O
" O
phenotype O
. O

Low O
activity O
of O
patient O
plasma O
butyrylcholinesterase O
with O
butyrylthiocholine O
( O
BTC B
) O
and O
benzoylcholine B
, O
and O
values O
of O
dibucaine B
and O
fluoride B
numbers O
fit O
with O
heterozygous O
atypical O
silent O
genotype O
. O

Electrophoretic O
analysis O
of O
plasma O
BChE O
of O
the O
proband O
and O
his O
mother O
showed O
that O
patient O
has O
a O
reduced O
amount O
of O
tetrameric O
enzyme O
in O
plasma O
and O
that O
minor O
fast O
- O
moving O
BChE O
components O
: O
monomer O
, O
dimer O
, O
and O
monomer O
- O
albumin O
conjugate O
are O
missing O
. O

Kinetic O
analysis O
showed O
that O
the O
p O
. O
Val204Asp O
/ O
p O
. O
Asp70Gly O
- O
p O
. O
Ala539Thr O
BChE O
displays O
a O
pure O
Michaelian O
behavior O
with O
BTC B
as O
the O
substrate O
. O

Both O
catalytic O
parameters O
Km O
= O
265 O
uM O
for O
BTC B
, O
two O
times O
higher O
than O
that O
of O
the O
atypical O
enzyme O
, O
and O
a O
low O
Vmax O
are O
consistent O
with O
the O
absence O
of O
activity O
against O
suxamethonium B
. O

Molecular O
dynamic O
( O
MD O
) O
simulations O
showed O
that O
the O
overall O
effect O
of O
the O
mutation O
p O
. O
Val204Asp O
is O
disruption O
of O
hydrogen O
bonding O
between O
Gln223 O
and O
Glu441 O
, O
leading O
Ser198 O
and O
His438 O
to O
move O
away O
from O
each O
other O
with O
subsequent O
disruption O
of O
the O
catalytic O
triad O
functionality O
regardless O
of O
the O
type O
of O
substrate O
. O

MD O
also O
showed O
that O
the O
enzyme O
volume O
is O
increased O
, O
suggesting O
a O
pre O
- O
denaturation O
state O
. O

This O
fits O
with O
the O
reduced O
concentration O
of O
p O
. O
Ala204Asp O
/ O
p O
. O
Asp70Gly O
- O
p O
. O
Ala539Thr O
tetrameric O
enzyme O
in O
the O
plasma O
and O
non O
- O
detectable O
fast O
moving O
- O
bands O
on O
electrophoresis O
gels O
. O

Delayed O
anemia O
after O
treatment O
with O
injectable O
artesunate B
in O
the O
Democratic O
Republic O
of O
the O
Congo O
: O
a O
manageable O
issue O
. O

Cases O
of O
delayed O
hemolytic O
anemia O
have O
been O
described O
after O
treatment O
with O
injectable O
artesunate B
, O
the O
current O
World O
Health O
Organization O
( O
WHO O
) O
- O
recommended O
first O
- O
line O
drug O
for O
the O
treatment O
of O
severe O
malaria O
. O

A O
total O
of O
350 O
patients O
( O
215 O
[ O
61 O
. O
4 O
% O
] O
< O
5 O
years O
of O
age O
and O
135 O
[ O
38 O
. O
6 O
% O
] O
> O
5 O
years O
of O
age O
) O
were O
followed O
- O
up O
after O
treatment O
with O
injectable O
artesunate B
for O
severe O
malaria O
in O
hospitals O
and O
health O
centers O
of O
the O
Democratic O
Republic O
of O
the O
Congo O
. O

Complete O
series O
of O
hemoglobin O
( O
Hb O
) O
measurements O
were O
available O
for O
201 O
patients O
. O

A O
decrease O
in O
Hb O
levels O
between O
2 O
and O
5 O
g O
/ O
dL O
was O
detected O
in O
23 O
( O
11 O
. O
4 O
% O
) O
patients O
during O
the O
follow O
- O
up O
period O
. O

For O
five O
patients O
, O
Hb O
levels O
decreased O
below O
5 O
g O
/ O
dL O
during O
at O
least O
one O
follow O
- O
up O
visit O
. O

All O
cases O
of O
delayed O
anemia O
were O
clinically O
manageable O
and O
resolved O
within O
one O
month O
. O

Regulation O
of O
signal O
transducer O
and O
activator O
of O
transcription O
3 O
and O
apoptotic O
pathways O
by O
betaine B
attenuates O
isoproterenol B
- O
induced O
acute O
myocardial O
injury O
in O
rats O
. O

The O
present O
study O
was O
designed O
to O
investigate O
the O
cardioprotective O
effects O
of O
betaine B
on O
acute O
myocardial O
ischemia O
induced O
experimentally O
in O
rats O
focusing O
on O
regulation O
of O
signal O
transducer O
and O
activator O
of O
transcription O
3 O
( O
STAT3 O
) O
and O
apoptotic O
pathways O
as O
the O
potential O
mechanism O
underlying O
the O
drug O
effect O
. O

Male O
Sprague O
Dawley O
rats O
were O
treated O
with O
betaine B
( O
100 O
, O
200 O
, O
and O
400 O
mg O
/ O
kg O
) O
orally O
for O
40 O
days O
. O

Acute O
myocardial O
ischemic O
injury O
was O
induced O
in O
rats O
by O
subcutaneous O
injection O
of O
isoproterenol B
( O
85 O
mg O
/ O
kg O
) O
, O
for O
two O
consecutive O
days O
. O

Serum O
cardiac O
marker O
enzyme O
, O
histopathological O
variables O
and O
expression O
of O
protein O
levels O
were O
analyzed O
. O

Oral O
administration O
of O
betaine B
( O
200 O
and O
400 O
mg O
/ O
kg O
) O
significantly O
reduced O
the O
level O
of O
cardiac O
marker O
enzyme O
in O
the O
serum O
and O
prevented O
left O
ventricular O
remodeling O
. O

Western O
blot O
analysis O
showed O
that O
isoproterenol B
- O
induced O
phosphorylation O
of O
STAT3 O
was O
maintained O
or O
further O
enhanced O
by O
betaine B
treatment O
in O
myocardium O
. O

Furthermore O
, O
betaine B
( O
200 O
and O
400 O
mg O
/ O
kg O
) O
treatment O
increased O
the O
ventricular O
expression O
of O
Bcl O
- O
2 O
and O
reduced O
the O
level O
of O
Bax O
, O
therefore O
causing O
a O
significant O
increase O
in O
the O
ratio O
of O
Bcl O
- O
2 O
/ O
Bax O
. O

The O
protective O
role O
of O
betaine B
on O
myocardial O
damage O
was O
further O
confirmed O
by O
histopathological O
examination O
. O

In O
summary O
, O
our O
results O
showed O
that O
betaine B
pretreatment O
attenuated O
isoproterenol B
- O
induced O
acute O
myocardial O
ischemia O
via O
the O
regulation O
of O
STAT3 O
and O
apoptotic O
pathways O
. O

Quetiapine B
- O
induced O
neutropenia O
in O
a O
bipolar O
patient O
with O
hepatocellular O
carcinoma O
. O

OBJECTIVE O
: O
Quetiapine B
is O
a O
dibenzothiazepine B
derivative O
, O
similar O
to O
clozapine B
, O
which O
has O
the O
highest O
risk O
of O
causing O
blood O
dyscrasias O
, O
especially O
neutropenia O
. O

There O
are O
some O
case O
reports O
about O
this O
side O
effect O
of O
quetiapine B
, O
but O
possible O
risk O
factors O
are O
seldom O
discussed O
and O
identified O
. O

A O
case O
of O
a O
patient O
with O
hepatocellular O
carcinoma O
that O
developed O
neutropenia O
after O
treatment O
with O
quetiapine B
is O
described O
here O
. O

CASE O
REPORT O
: O
A O
62 O
- O
year O
- O
old O
Taiwanese O
widow O
with O
bipolar O
disorder O
was O
diagnosed O
with O
hepatocellular O
carcinoma O
at O
age O
60 O
. O

She O
developed O
leucopenia O
after O
being O
treated O
with O
quetiapine B
. O

After O
quetiapine B
was O
discontinued O
, O
her O
white O
blood O
cell O
count O
returned O
to O
normal O
. O

CONCLUSIONS O
: O
Although O
neutropenia O
is O
not O
a O
common O
side O
effect O
of O
quetiapine B
, O
physicians O
should O
be O
cautious O
about O
its O
presentation O
and O
associated O
risk O
factors O
. O

Hepatic O
dysfunction O
may O
be O
one O
of O
the O
possible O
risk O
factors O
, O
and O
concomitant O
fever O
may O
be O
a O
diagnostic O
marker O
for O
adverse O
reaction O
to O
quetiapine B
. O

Lateral O
antebrachial O
cutaneous O
neuropathy O
after O
steroid B
injection O
at O
lateral O
epicondyle O
. O

BACKGROUND O
AND O
OBJECTIVES O
: O
This O
report O
aimed O
to O
present O
a O
case O
of O
lateral O
antebrachial O
cutaneous O
neuropathy O
( O
LACNP O
) O
that O
occurred O
after O
a O
steroid B
injection O
in O
the O
lateral O
epicondyle O
to O
treat O
lateral O
epicondylitis O
in O
a O
40 O
- O
year O
- O
old O
woman O
. O

MATERIAL O
AND O
METHOD O
: O
A O
40 O
- O
year O
- O
old O
woman O
presented O
with O
decreased O
sensation O
and O
paresthesia O
over O
her O
right O
lateral O
forearm O
; O
the O
paresthesia O
had O
occurred O
after O
a O
steroid B
injection O
in O
the O
right O
lateral O
epicondyle O
3 O
months O
before O
. O

Her O
sensation O
of O
light O
touch O
and O
pain O
was O
diminished O
over O
the O
lateral O
side O
of O
the O
right O
forearm O
and O
wrist O
area O
. O

RESULTS O
: O
The O
sensory O
action O
potential O
amplitude O
of O
the O
right O
lateral O
antebrachial O
cutaneous O
nerve O
( O
LACN O
) O
( O
6 O
. O
2 O
uV O
) O
was O
lower O
than O
that O
of O
the O
left O
( O
13 O
. O
1 O
uV O
) O
. O

The O
difference O
of O
amplitude O
between O
both O
sides O
was O
significant O
because O
there O
was O
more O
than O
a O
50 O
% O
reduction O
. O

She O
was O
diagnosed O
with O
right O
LACNP O
( O
mainly O
axonal O
involvement O
) O
on O
the O
basis O
of O
the O
clinical O
manifestation O
and O
the O
electrodiagnostic O
findings O
. O

Her O
symptoms O
improved O
through O
physical O
therapy O
but O
persisted O
to O
some O
degree O
. O

CONCLUSION O
: O
This O
report O
describes O
the O
case O
of O
a O
woman O
with O
LACNP O
that O
developed O
after O
a O
steroid B
injection O
for O
the O
treatment O
of O
lateral O
epicondylitis O
. O

An O
electrodiagnostic O
study O
, O
including O
a O
nerve O
conduction O
study O
of O
the O
LACN O
, O
was O
helpful O
to O
diagnose O
right O
LACNP O
and O
to O
find O
the O
passage O
of O
the O
LACN O
on O
the O
lateral O
epicondyle O
. O

Curcumin B
prevents O
maleate B
- O
induced O
nephrotoxicity O
: O
relation O
to O
hemodynamic O
alterations O
, O
oxidative O
stress O
, O
mitochondrial O
oxygen B
consumption O
and O
activity O
of O
respiratory O
complex O
I O
. O

The O
potential O
protective O
effect O
of O
the O
dietary O
antioxidant O
curcumin B
( O
120 O
mg O
/ O
Kg O
/ O
day O
for O
6 O
days O
) O
against O
the O
renal O
injury O
induced O
by O
maleate B
was O
evaluated O
. O

Tubular O
proteinuria O
and O
oxidative O
stress O
were O
induced O
by O
a O
single O
injection O
of O
maleate B
( O
400 O
mg O
/ O
kg O
) O
in O
rats O
. O

Maleate B
- O
induced O
renal O
injury O
included O
increase O
in O
renal O
vascular O
resistance O
and O
in O
the O
urinary O
excretion O
of O
total O
protein O
, O
glucose B
, O
sodium B
, O
neutrophil O
gelatinase O
- O
associated O
lipocalin O
( O
NGAL O
) O
and O
N O
- O
acetyl O
b O
- O
D O
- O
glucosaminidase O
( O
NAG O
) O
, O
upregulation O
of O
kidney O
injury O
molecule O
( O
KIM O
) O
- O
1 O
, O
decrease O
in O
renal O
blood O
flow O
and O
claudin O
- O
2 O
expression O
besides O
of O
necrosis O
and O
apoptosis O
of O
tubular O
cells O
on O
24 O
h O
. O

Oxidative O
stress O
was O
determined O
by O
measuring O
the O
oxidation O
of O
lipids O
and O
proteins O
and O
diminution O
in O
renal O
Nrf2 O
levels O
. O

Studies O
were O
also O
conducted O
in O
renal O
epithelial O
LLC O
- O
PK1 O
cells O
and O
in O
mitochondria O
isolated O
from O
kidneys O
of O
all O
the O
experimental O
groups O
. O

Maleate B
induced O
cell O
damage O
and O
reactive O
oxygen B
species O
( O
ROS O
) O
production O
in O
LLC O
- O
PK1 O
cells O
in O
culture O
. O

In O
addition O
, O
maleate B
treatment O
reduced O
oxygen B
consumption O
in O
ADP B
- O
stimulated O
mitochondria O
and O
diminished O
respiratory O
control O
index O
when O
using O
malate B
/ O
glutamate B
as O
substrate O
. O

The O
activities O
of O
both O
complex O
I O
and O
aconitase O
were O
also O
diminished O
. O

All O
the O
above O
- O
described O
alterations O
were O
prevented O
by O
curcumin B
. O

It O
is O
concluded O
that O
curcumin B
is O
able O
to O
attenuate O
in O
vivo O
maleate B
- O
induced O
nephropathy O
and O
in O
vitro O
cell O
damage O
. O

The O
in O
vivo O
protection O
was O
associated O
to O
the O
prevention O
of O
oxidative O
stress O
and O
preservation O
of O
mitochondrial O
oxygen B
consumption O
and O
activity O
of O
respiratory O
complex O
I O
, O
and O
the O
in O
vitro O
protection O
was O
associated O
to O
the O
prevention O
of O
ROS O
production O
. O

Anticonvulsant O
actions O
of O
MK B
- I
801 I
on O
the O
lithium B
- O
pilocarpine B
model O
of O
status O
epilepticus O
in O
rats O
. O

MK B
- I
801 I
, O
a O
noncompetitive O
N B
- I
methyl I
- I
D I
- I
aspartate I
( O
NMDA B
) O
receptor O
antagonist O
, O
was O
tested O
for O
anticonvulsant O
effects O
in O
rats O
using O
two O
seizure O
models O
, O
coadministration O
of O
lithium B
and O
pilocarpine B
and O
administration O
of O
a O
high O
dose O
of O
pilocarpine B
alone O
. O

Three O
major O
results O
are O
reported O
. O

First O
, O
pretreatment O
with O
MK B
- I
801 I
produced O
an O
effective O
and O
dose O
- O
dependent O
anticonvulsant O
action O
with O
the O
lithium B
- O
pilocarpine B
model O
but O
not O
with O
rats O
treated O
with O
pilocarpine B
alone O
, O
suggesting O
that O
different O
biochemical O
mechanisms O
control O
seizures O
in O
these O
two O
models O
. O

Second O
, O
the O
anticonvulsant O
effect O
of O
MK B
- I
801 I
in O
the O
lithium B
- O
pilocarpine B
model O
only O
occurred O
after O
initial O
periods O
of O
seizure O
activity O
. O

This O
observation O
is O
suggested O
to O
be O
an O
in O
vivo O
demonstration O
of O
the O
conclusion O
derived O
from O
in O
vitro O
experiments O
that O
MK B
- I
801 I
binding O
requires O
agonist O
- O
induced O
opening O
of O
the O
channel O
sites O
of O
the O
NMDA B
receptor O
. O

Third O
, O
although O
it O
is O
relatively O
easy O
to O
block O
seizures O
induced O
by O
lithium B
and O
pilocarpine B
by O
administration O
of O
anticonvulsants O
prior O
to O
pilocarpine B
, O
it O
is O
more O
difficult O
to O
terminate O
ongoing O
status O
epilepticus O
and O
block O
the O
lethality O
of O
the O
seizures O
. O

Administration O
of O
MK B
- I
801 I
30 O
or O
60 O
min O
after O
pilocarpine B
, O
i O
. O
e O
. O
, O
during O
status O
epilepticus O
, O
gradually O
reduced O
electrical O
and O
behavioral O
seizure O
activity O
and O
greatly O
enhanced O
the O
survival O
rate O
. O

These O
results O
suggest O
that O
activation O
of O
NMDA B
receptors O
plays O
an O
important O
role O
in O
status O
epilepticus O
and O
brain O
damage O
in O
the O
lithium B
- O
pilocarpine B
model O
. O

This O
was O
further O
supported O
by O
results O
showing O
that O
nonconvulsive O
doses O
of O
NMDA B
and O
pilocarpine B
were O
synergistic O
, O
resulting O
in O
status O
epilepticus O
and O
subsequent O
mortality O
. O

Continuous O
infusion O
tobramycin B
combined O
with O
carbenicillin B
for O
infections O
in O
cancer O
patients O
. O

The O
cure O
rate O
of O
infections O
in O
cancer O
patients O
is O
adversely O
affected O
by O
neutropenia O
( O
less O
than O
1 O
, O
000 O
/ O
mm3 O
) O
. O

In O
particular O
, O
patients O
with O
severe O
neutropenia O
( O
less O
than O
100 O
/ O
mm3 O
) O
have O
shown O
a O
poor O
response O
to O
antibiotics O
. O

To O
overcome O
the O
adverse O
effects O
of O
neutropenia O
, O
tobramycin B
was O
given O
by O
continuous O
infusion O
and O
combined O
with O
intermittent O
carbenicillin B
. O

Tobramycin B
was O
given O
to O
a O
total O
daily O
dose O
of O
300 O
mg O
/ O
m2 O
and O
carbenicillin B
was O
given O
at O
a O
dose O
of O
5 O
gm O
every O
four O
hours O
. O

There O
were O
125 O
infectious O
episodes O
in O
116 O
cancer O
patients O
receiving O
myelosuppressive O
chemotherapy O
. O

The O
overall O
cure O
rate O
was O
70 O
% O
. O

Pneumonia O
was O
the O
most O
common O
infection O
and O
61 O
% O
of O
59 O
episodes O
were O
cured O
. O

Gram O
- O
negative O
bacilli O
were O
the O
most O
common O
causative O
organisms O
and O
69 O
% O
of O
these O
infections O
were O
cured O
. O

The O
most O
common O
pathogen O
was O
Klebsiella O
pneumoniae O
and O
this O
, O
together O
with O
Escherichia O
coli O
and O
Pseudomonas O
aeruginosa O
, O
accounted O
for O
74 O
% O
of O
all O
gram O
- O
negative O
bacillary O
infections O
. O

Response O
was O
not O
influenced O
by O
the O
initial O
neutrophil O
count O
, O
with O
a O
62 O
% O
cure O
rate O
for O
39 O
episodes O
associated O
with O
severe O
neutropenia O
. O

However O
, O
failure O
of O
the O
neutrophil O
count O
to O
increase O
during O
therapy O
adversely O
affected O
response O
. O

Azotemia O
was O
the O
major O
side O
effect O
recognized O
, O
and O
it O
occurred O
in O
11 O
% O
of O
episodes O
. O

Major O
azotemia O
( O
serum O
creatinine B
greater O
than O
2 O
. O
5 O
mg O
/ O
dl O
or O
BUN B
greater O
than O
50 O
mg O
/ O
dl O
) O
occurred O
in O
only O
2 O
% O
. O

Azotemia O
was O
not O
related O
to O
duration O
of O
therapy O
or O
serum O
tobramycin B
concentration O
. O

This O
antibiotic O
regimen O
showed O
both O
therapeutic O
efficacy O
and O
acceptable O
renal O
toxicity O
for O
these O
patients O
. O

Incidence O
of O
solid O
tumours O
among O
pesticide O
applicators O
exposed O
to O
the O
organophosphate B
insecticide O
diazinon B
in O
the O
Agricultural O
Health O
Study O
: O
an O
updated O
analysis O
. O

OBJECTIVE O
: O
Diazinon B
, O
a O
common O
organophosphate B
insecticide O
with O
genotoxic O
properties O
, O
was O
previously O
associated O
with O
lung O
cancer O
in O
the O
Agricultural O
Health O
Study O
( O
AHS O
) O
cohort O
, O
but O
few O
other O
epidemiological O
studies O
have O
examined O
diazinon B
- O
associated O
cancer O
risk O
. O

We O
used O
updated O
diazinon B
exposure O
and O
cancer O
incidence O
information O
to O
evaluate O
solid O
tumour O
risk O
in O
the O
AHS O
. O

METHODS O
: O
Male O
pesticide O
applicators O
in O
Iowa O
and O
North O
Carolina O
reported O
lifetime O
diazinon B
use O
at O
enrolment O
( O
1993 O
- O
1997 O
) O
and O
follow O
- O
up O
( O
1998 O
- O
2005 O
) O
; O
cancer O
incidence O
was O
assessed O
through O
2010 O
( O
North O
Carolina O
) O
/ O
2011 O
( O
Iowa O
) O
. O

Among O
applicators O
with O
usage O
information O
sufficient O
to O
evaluate O
exposure O
- O
response O
patterns O
, O
we O
used O
Poisson O
regression O
to O
estimate O
adjusted O
rate O
ratios O
( O
RRs O
) O
and O
95 O
% O
CI O
for O
cancer O
sites O
with O
> O
10 O
exposed O
cases O
for O
both O
lifetime O
( O
LT O
) O
exposure O
days O
and O
intensity O
- O
weighted O
( O
IW O
) O
lifetime O
exposure O
days O
( O
accounting O
for O
factors O
impacting O
exposure O
) O
. O

RESULTS O
: O
We O
observed O
elevated O
lung O
cancer O
risks O
( O
N O
= O
283 O
) O
among O
applicators O
with O
the O
greatest O
number O
of O
LT O
( O
RR O
= O
1 O
. O
60 O
; O
95 O
% O
CI O
1 O
. O
11 O
to O
2 O
. O
31 O
; O
Ptrend O
= O
0 O
. O
02 O
) O
and O
IW O
days O
of O
diazinon B
use O
( O
RR O
= O
1 O
. O
41 O
; O
95 O
% O
CI O
0 O
. O
98 O
to O
2 O
. O
04 O
; O
Ptrend O
= O
0 O
. O
08 O
) O
. O

Kidney O
cancer O
( O
N O
= O
94 O
) O
risks O
were O
non O
- O
significantly O
elevated O
( O
RRLT O
days O
= O
1 O
. O
77 O
; O
95 O
% O
CI O
0 O
. O
90 O
to O
3 O
. O
51 O
; O
Ptrend O
= O
0 O
. O
09 O
; O
RRIW O
days O
1 O
. O
37 O
; O
95 O
% O
CI O
0 O
. O
64 O
to O
2 O
. O
92 O
; O
Ptrend O
= O
0 O
. O
50 O
) O
, O
as O
were O
risks O
for O
aggressive O
prostate O
cancer O
( O
N O
= O
656 O
) O
. O

CONCLUSIONS O
: O
Our O
updated O
evaluation O
of O
diazinon B
provides O
additional O
evidence O
of O
an O
association O
with O
lung O
cancer O
risk O
. O

Newly O
identified O
links O
to O
kidney O
cancer O
and O
associations O
with O
aggressive O
prostate O
cancer O
require O
further O
evaluation O
. O

Associations O
of O
Ozone B
and O
PM2 O
. O
5 O
Concentrations O
With O
Parkinson O
' O
s O
Disease O
Among O
Participants O
in O
the O
Agricultural O
Health O
Study O
. O

OBJECTIVE O
: O
This O
study O
describes O
associations O
of O
ozone B
and O
fine O
particulate O
matter O
with O
Parkinson O
' O
s O
disease O
observed O
among O
farmers O
in O
North O
Carolina O
and O
Iowa O
. O

METHODS O
: O
We O
used O
logistic O
regression O
to O
determine O
the O
associations O
of O
these O
pollutants B
with O
self O
- O
reported O
, O
doctor O
- O
diagnosed O
Parkinson O
' O
s O
disease O
. O

Daily O
predicted O
pollutant O
concentrations O
were O
used O
to O
derive O
surrogates O
of O
long O
- O
term O
exposure O
and O
link O
them O
to O
study O
participants O
' O
geocoded O
addresses O
. O

RESULTS O
: O
We O
observed O
positive O
associations O
of O
Parkinson O
' O
s O
disease O
with O
ozone B
( O
odds O
ratio O
= O
1 O
. O
39 O
; O
95 O
% O
CI O
: O
0 O
. O
98 O
to O
1 O
. O
98 O
) O
and O
fine O
particulate O
matter O
( O
odds O
ratio O
= O
1 O
. O
34 O
; O
95 O
% O
CI O
: O
0 O
. O
93 O
to O
1 O
. O
93 O
) O
in O
North O
Carolina O
but O
not O
in O
Iowa O
. O

CONCLUSIONS O
: O
The O
plausibility O
of O
an O
effect O
of O
ambient O
concentrations O
of O
these O
pollutants O
on O
Parkinson O
' O
s O
disease O
risk O
is O
supported O
by O
experimental O
data O
demonstrating O
damage O
to O
dopaminergic O
neurons O
at O
relevant O
concentrations O
. O

Additional O
studies O
are O
needed O
to O
address O
uncertainties O
related O
to O
confounding O
and O
to O
examine O
temporal O
aspects O
of O
the O
associations O
we O
observed O
. O

Low O
functional O
programming O
of O
renal O
AT2R O
mediates O
the O
developmental O
origin O
of O
glomerulosclerosis O
in O
adult O
offspring O
induced O
by O
prenatal O
caffeine B
exposure O
. O

UNASSIGNED O
: O
Our O
previous O
study O
has O
indicated O
that O
prenatal O
caffeine B
exposure O
( O
PCE O
) O
could O
induce O
intrauterine O
growth O
retardation O
( O
IUGR O
) O
of O
offspring O
. O

Recent O
research O
suggested O
that O
IUGR O
is O
a O
risk O
factor O
for O
glomerulosclerosis O
. O

However O
, O
whether O
PCE B
could O
induce O
glomerulosclerosis O
and O
its O
underlying O
mechanisms O
remain O
unknown O
. O

This O
study O
aimed O
to O
demonstrate O
the O
induction O
to O
glomerulosclerosis O
in O
adult O
offspring O
by O
PCE B
and O
its O
intrauterine O
programming O
mechanisms O
. O

A O
rat O
model O
of O
IUGR O
was O
established O
by O
PCE B
, O
male O
fetuses O
and O
adult O
offspring O
at O
the O
age O
of O
postnatal O
week O
24 O
were O
euthanized O
. O

The O
results O
revealed O
that O
the O
adult O
offspring O
kidneys O
in O
the O
PCE B
group O
exhibited O
glomerulosclerosis O
as O
well O
as O
interstitial O
fibrosis O
, O
accompanied O
by O
elevated O
levels O
of O
serum O
creatinine B
and O
urine O
protein O
. O

Renal O
angiotensin B
II I
receptor O
type O
2 O
( O
AT2R O
) O
gene O
expression O
in O
adult O
offspring O
was O
reduced O
by O
PCE B
, O
whereas O
the O
renal O
angiotensin B
II I
receptor O
type O
1a O
( O
AT1aR O
) O
/ O
AT2R O
expression O
ratio O
was O
increased O
. O

The O
fetal O
kidneys O
in O
the O
PCE B
group O
displayed O
an O
enlarged O
Bowman O
' O
s O
space O
and O
a O
shrunken O
glomerular O
tuft O
, O
accompanied O
by O
a O
reduced O
cortex O
width O
and O
an O
increase O
in O
the O
nephrogenic O
zone O
/ O
cortical O
zone O
ratio O
. O

Observation O
by O
electronic O
microscope O
revealed O
structural O
damage O
of O
podocytes O
; O
the O
reduced O
expression O
level O
of O
podocyte O
marker O
genes O
, O
nephrin O
and O
podocin O
, O
was O
also O
detected O
by O
q O
- O
PCR O
. O

Moreover O
, O
AT2R O
gene O
and O
protein O
expressions O
in O
fetal O
kidneys O
were O
inhibited O
by O
PCE B
, O
associated O
with O
the O
repression O
of O
the O
gene O
expression O
of O
glial O
- O
cell O
- O
line O
- O
derived O
neurotrophic O
factor O
( O
GDNF O
) O
/ O
tyrosine B
kinase O
receptor O
( O
c O
- O
Ret O
) O
signaling O
pathway O
. O

These O
results O
demonstrated O
that O
PCE B
could O
induce O
dysplasia O
of O
fetal O
kidneys O
as O
well O
as O
glomerulosclerosis O
of O
adult O
offspring O
, O
and O
the O
low O
functional O
programming O
of O
renal O
AT2R O
might O
mediate O
the O
developmental O
origin O
of O
adult O
glomerulosclerosis O
. O

1 B
, I
3 I
- I
Butadiene I
, O
CML O
and O
the O
t O
( O
9 O
: O
22 O
) O
translocation O
: O
A O
reality O
check O
. O

UNASSIGNED O
: O
Epidemiological O
studies O
of O
1 B
, I
3 I
- I
butadiene I
have O
suggest O
that O
exposures O
to O
humans O
are O
associated O
with O
chronic O
myeloid O
leukemia O
( O
CML O
) O
. O

CML O
has O
a O
well O
- O
documented O
association O
with O
ionizing O
radiation O
, O
but O
reports O
of O
associations O
with O
chemical O
exposures O
have O
been O
questioned O
. O

Ionizing O
radiation O
is O
capable O
of O
inducing O
the O
requisite O
CML O
- O
associated O
t O
( O
9 O
: O
22 O
) O
translocation O
( O
Philadelphia O
chromosome O
) O
in O
appropriate O
cells O
in O
vitro O
but O
, O
thus O
far O
, O
chemicals O
have O
not O
shown O
this O
capacity O
. O

We O
have O
proposed O
that O
1 B
, I
3 I
- I
butadiene I
metabolites O
be O
so O
tested O
as O
a O
reality O
check O
on O
the O
epidemiological O
reports O
. O

In O
order O
to O
conduct O
reliable O
testing O
in O
this O
regard O
, O
it O
is O
essential O
that O
a O
positive O
control O
for O
induction O
be O
available O
. O

We O
have O
used O
ionizing O
radiation O
to O
develop O
such O
a O
control O
. O

Results O
described O
here O
demonstrate O
that O
this O
agent O
does O
in O
fact O
induce O
pathogenic O
t O
( O
9 O
: O
22 O
) O
translocations O
in O
a O
human O
myeloid O
cell O
line O
in O
vitro O
, O
but O
does O
so O
at O
low O
frequencies O
. O

Conditions O
that O
will O
be O
required O
for O
studies O
of O
1 B
, I
3 I
- I
butadiene I
are O
discussed O
. O

Cancer O
incidence O
and O
metolachlor B
use O
in O
the O
Agricultural O
Health O
Study O
: O
An O
update O
. O

UNASSIGNED O
: O
Metolachlor B
, O
a O
widely O
used O
herbicide O
, O
is O
classified O
as O
a O
Group O
C O
carcinogen O
by O
the O
U O
. O
S O
. O

Environmental O
Protection O
Agency O
based O
on O
increased O
liver O
neoplasms O
in O
female O
rats O
. O

Epidemiologic O
studies O
of O
the O
health O
effects O
of O
metolachlor B
have O
been O
limited O
. O

The O
Agricultural O
Health O
Study O
( O
AHS O
) O
is O
a O
prospective O
cohort O
study O
including O
licensed O
private O
and O
commercial O
pesticide O
applicators O
in O
Iowa O
and O
North O
Carolina O
enrolled O
1993 O
- O
1997 O
. O

We O
evaluated O
cancer O
incidence O
through O
2010 O
/ O
2011 O
( O
NC O
/ O
IA O
) O
for O
49 O
, O
616 O
applicators O
, O
53 O
% O
of O
whom O
reported O
ever O
using O
metolachlor B
. O

We O
used O
Poisson O
regression O
to O
evaluate O
relations O
between O
two O
metrics O
of O
metolachlor B
use O
( O
lifetime O
days O
, O
intensity O
- O
weighted O
lifetime O
days O
) O
and O
cancer O
incidence O
. O

We O
saw O
no O
association O
between O
metolachlor B
use O
and O
incidence O
of O
all O
cancers O
combined O
( O
n O
= O
5 O
, O
701 O
with O
a O
5 O
- O
year O
lag O
) O
or O
most O
site O
- O
specific O
cancers O
. O

For O
liver O
cancer O
, O
in O
analyses O
restricted O
to O
exposed O
workers O
, O
elevations O
observed O
at O
higher O
categories O
of O
use O
were O
not O
statistically O
significant O
. O

However O
, O
trends O
for O
both O
lifetime O
and O
intensity O
- O
weighted O
lifetime O
days O
of O
metolachor B
use O
were O
positive O
and O
statistically O
significant O
with O
an O
unexposed O
reference O
group O
. O

A O
similar O
pattern O
was O
observed O
for O
follicular O
cell O
lymphoma O
, O
but O
no O
other O
lymphoma O
subtypes O
. O

An O
earlier O
suggestion O
of O
increased O
lung O
cancer O
risk O
at O
high O
levels O
of O
metolachlor B
use O
in O
this O
cohort O
was O
not O
confirmed O
in O
this O
update O
. O

This O
suggestion O
of O
an O
association O
between O
metolachlor B
and O
liver O
cancer O
among O
pesticide O
applicators O
is O
a O
novel O
finding O
and O
echoes O
observation O
of O
increased O
liver O
neoplasms O
in O
some O
animal O
studies O
. O

However O
, O
our O
findings O
for O
both O
liver O
cancer O
and O
follicular O
cell O
lymphoma O
warrant O
follow O
- O
up O
to O
better O
differentiate O
effects O
of O
metolachlor B
use O
from O
other O
factors O
. O

Mechanisms O
Underlying O
Latent O
Disease O
Risk O
Associated O
with O
Early O
- O
Life O
Arsenic B
Exposure O
: O
Current O
Research O
Trends O
and O
Scientific O
Gaps O
. O

BACKGROUND O
: O
Millions O
of O
individuals O
worldwide O
, O
particularly O
those O
living O
in O
rural O
and O
developing O
areas O
, O
are O
exposed O
to O
harmful O
levels O
of O
inorganic O
arsenic B
( O
iAs B
) O
in O
their O
drinking O
water O
. O

Inorganic O
As B
exposure O
during O
key O
developmental O
periods O
is O
associated O
with O
a O
variety O
of O
adverse O
health O
effects O
including O
those O
that O
are O
evident O
in O
adulthood O
. O

There O
is O
considerable O
interest O
in O
identifying O
the O
molecular O
mechanisms O
that O
relate O
early O
- O
life O
iAs B
exposure O
to O
the O
development O
of O
these O
latent O
diseases O
, O
particularly O
in O
relationship O
to O
cancer O
. O

OBJECTIVES O
: O
This O
work O
summarizes O
research O
on O
the O
molecular O
mechanisms O
that O
underlie O
the O
increased O
risk O
of O
cancer O
development O
in O
adulthood O
that O
is O
associated O
with O
early O
- O
life O
iAs B
exposure O
. O

DISCUSSION O
: O
Epigenetic O
reprogramming O
that O
imparts O
functional O
changes O
in O
gene O
expression O
, O
the O
development O
of O
cancer O
stem O
cells O
, O
and O
immunomodulation O
are O
plausible O
underlying O
mechanisms O
by O
which O
early O
- O
life O
iAs B
exposure O
elicits O
latent O
carcinogenic O
effects O
. O

CONCLUSIONS O
: O
Evidence O
is O
mounting O
that O
relates O
early O
- O
life O
iAs B
exposure O
and O
cancer O
development O
later O
in O
life O
. O

Future O
research O
should O
include O
animal O
studies O
that O
address O
mechanistic O
hypotheses O
and O
studies O
of O
human O
populations O
that O
integrate O
early O
- O
life O
exposure O
, O
molecular O
alterations O
, O
and O
latent O
disease O
outcomes O
. O

Nifedipine B
induced O
bradycardia O
in O
a O
patient O
with O
autonomic O
neuropathy O
. O

An O
80 O
year O
old O
diabetic O
male O
with O
evidence O
of O
peripheral O
and O
autonomic O
neuropathy O
was O
admitted O
with O
chest O
pain O
. O

He O
was O
found O
to O
have O
atrial O
flutter O
at O
a O
ventricular O
rate O
of O
70 O
/ O
min O
which O
slowed O
down O
to O
30 O
- O
40 O
/ O
min O
when O
nifedipine B
( O
60 O
mg O
) O
in O
3 O
divided O
doses O
, O
during O
which O
he O
was O
paced O
at O
a O
rate O
of O
70 O
/ O
min O
. O

This O
is O
inconsistent O
with O
the O
well O
- O
established O
finding O
that O
nifedipine B
induces O
tachycardia O
in O
normally O
innervated O
hearts O
. O

However O
, O
in O
hearts O
deprived O
of O
compensatory O
sympathetic O
drive O
, O
it O
may O
lead O
to O
bradycardia O
. O

The O
effect O
of O
haloperidol B
in O
cocaine B
and O
amphetamine B
intoxication O
. O

The O
effectiveness O
of O
haloperidol B
pretreatment O
in O
preventing O
the O
toxic O
effects O
of O
high O
doses O
of O
amphetamine B
and O
cocaine B
was O
studied O
in O
rats O
. O

In O
this O
model O
, O
toxic O
effects O
were O
induced O
by O
intraperitoneal O
( O
i O
. O
p O
. O
) O
injection O
of O
amphetamine B
75 O
mg O
/ O
kg O
( O
100 O
% O
death O
rate O
) O
or O
cocaine B
70 O
mg O
/ O
kg O
( O
82 O
% O
death O
rate O
) O
. O

Haloperidol B
failed O
to O
prevent O
amphetamine B
- O
induced O
seizures O
, O
but O
did O
lower O
the O
mortality O
rate O
at O
most O
doses O
tested O
. O

Haloperidol B
decreased O
the O
incidence O
of O
cocaine B
- O
induced O
seizures O
at O
the O
two O
highest O
doses O
, O
but O
the O
lowering O
of O
the O
mortality O
rate O
did O
not O
reach O
statistical O
significance O
at O
any O
dose O
. O

These O
data O
suggest O
a O
protective O
role O
for O
the O
central O
dopamine B
blocker O
haloperidol B
against O
death O
from O
high O
- O
dose O
amphetamine B
exposure O
without O
reducing O
the O
incidence O
of O
seizures O
. O

In O
contrast O
, O
haloperidol B
demonstrated O
an O
ability O
to O
reduce O
cocaine B
- O
induced O
seizures O
without O
significantly O
reducing O
mortality O
. O

Autoradiographic O
evidence O
of O
estrogen B
binding O
sites O
in O
nuclei O
of O
diethylstilbesterol B
induced O
hamster O
renal O
carcinomas O
. O

Estrogen B
binding O
sites O
were O
demonstrated O
by O
autoradiography O
in O
one O
transplantable O
and O
five O
primary O
diethylstilbesterol B
induced O
renal O
carcinomas O
in O
three O
hamsters O
. O

Radiolabelling O
, O
following O
the O
in O
vivo O
injection O
of O
3H B
- I
17 I
beta I
estradiol I
, O
was O
increased O
only O
over O
the O
nuclei O
of O
tumor O
cells O
; O
stereologic O
analysis O
revealed O
a O
4 O
. O
5 O
- O
to O
6 O
. O
7 O
- O
times O
higher O
concentration O
of O
reduced O
silver B
grains O
over O
nuclei O
than O
cytoplasm O
of O
these O
cells O
. O

Despite O
rapid O
tubular O
excretion O
of O
estradiol B
which O
peaked O
in O
less O
than O
1 O
h O
, O
the O
normal O
cells O
did O
not O
appear O
to O
bind O
the O
ligand O
. O

This O
is O
the O
first O
published O
report O
documenting O
the O
preferential O
in O
vivo O
binding O
of O
estrogen B
to O
nuclei O
of O
cells O
in O
estrogen B
induced O
hamster O
renal O
carcinomas O
. O

Bradycardia O
due O
to O
biperiden B
. O

In O
a O
38 O
- O
year O
- O
old O
male O
patient O
suffering O
from O
a O
severe O
postzosteric O
trigeminal O
neuralgia O
, O
intravenous O
application O
of O
10 O
mg O
biperiden B
lactate I
led O
to O
a O
long O
- O
lasting O
paradoxical O
reaction O
characterized O
by O
considerable O
bradycardia O
, O
dysarthria O
, O
and O
dysphagia O
. O

The O
heart O
rate O
was O
back O
to O
normal O
within O
12 O
hours O
upon O
administration O
of O
orciprenaline B
under O
cardiac O
monitoring O
in O
an O
intensive O
care O
unit O
. O

Bradycardia O
induced O
by O
biperiden B
is O
attributed O
to O
the O
speed O
of O
injection O
and O
to O
a O
dose O
- O
related O
dual O
effect O
of O
atropine B
- O
like O
drugs O
on O
muscarine B
receptors O
. O

Deliberate O
hypotension O
induced O
by O
labetalol B
with O
halothane B
, O
enflurane B
or O
isoflurane B
for O
middle O
- O
ear O
surgery O
. O

The O
feasibility O
of O
using O
labetalol B
, O
an O
alpha O
- O
and O
beta O
- O
adrenergic O
blocking O
agent O
, O
as O
a O
hypotensive O
agent O
in O
combination O
with O
inhalation O
anaesthetics O
( O
halothane B
, O
enflurane B
or O
isoflurane B
) O
was O
studied O
in O
23 O
adult O
patients O
undergoing O
middle O
- O
ear O
surgery O
. O

The O
mean O
arterial O
pressure O
was O
decreased O
from O
86 O
+ O
/ O
- O
5 O
( O
s O
. O
e O
. O
mean O
) O
mmHg O
to O
52 O
+ O
/ O
- O
1 O
mmHg O
( O
11 O
. O
5 O
+ O
/ O
- O
0 O
. O
7 O
to O
6 O
. O
9 O
+ O
/ O
- O
0 O
. O
1 O
kPa O
) O
for O
98 O
+ O
/ O
- O
10 O
min O
in O
the O
halothane B
( O
H O
) O
group O
, O
from O
79 O
+ O
/ O
- O
5 O
to O
53 O
+ O
/ O
- O
1 O
mmHg O
( O
10 O
. O
5 O
+ O
/ O
- O
0 O
. O
7 O
to O
7 O
. O
1 O
+ O
/ O
- O
0 O
. O
1 O
kPa O
) O
for O
129 O
+ O
/ O
- O
11 O
min O
in O
the O
enflurane B
( O

E O
) O
group O
, O
and O
from O
80 O
+ O
/ O
- O
4 O
to O
49 O
+ O
/ O
- O
1 O
mmHg O
( O
10 O
. O
7 O
+ O
/ O
- O
0 O
. O
5 O
to O
6 O
. O
5 O
+ O
/ O
- O
0 O
. O
1 O
kPa O
) O
for O
135 O
+ O
/ O
- O
15 O
min O
in O
the O
isoflurane B
( O
I O
) O
group O
. O

The O
mean O
H B
concentration O
during O
hypotension O
in O
the O
inspiratory O
gas O
was O
0 O
. O
7 O
+ O
/ O
- O
0 O
. O
1 O
vol O
% O
, O
the O
mean O
E O
concentration O
1 O
. O
6 O
+ O
/ O
- O
0 O
. O
2 O
vol O
% O
, O
and O
the O
mean O
I O
concentration O
1 O
. O
0 O
+ O
/ O
- O
0 O
. O
1 O
vol O
% O
. O

In O
addition O
, O
the O
patients O
received O
fentanyl B
and O
d B
- I
tubocurarine I
. O

The O
initial O
dose O
of O
labetalol B
for O
lowering O
blood O
pressure O
was O
similar O
, O
0 O
. O
52 O
- O
0 O
. O
59 O
mg O
/ O
kg O
, O
in O
all O
the O
groups O
. O

During O
hypotension O
, O
the O
heart O
rate O
was O
stable O
without O
tachy O
- O
or O
bradycardia O
. O

The O
operating O
conditions O
regarding O
bleeding O
were O
estimated O
in O
a O
double O
- O
blind O
manner O
, O
and O
did O
not O
differ O
significantly O
between O
the O
groups O
. O

During O
hypotension O
, O
the O
serum O
creatinine B
concentration O
rose O
significantly O
in O
all O
groups O
from O
the O
values O
before O
hypotension O
and O
returned O
postoperatively O
to O
the O
initial O
level O
in O
the O
other O
groups O
, O
except O
the O
isoflurane B
group O
. O

After O
hypotension O
there O
was O
no O
rebound O
phenomenon O
in O
either O
blood O
pressure O
or O
heart O
rate O
. O

These O
results O
indicate O
that O
labetalol B
induces O
easily O
adjustable O
hypotension O
without O
compensatory O
tachycardia O
and O
rebound O
hypertension O
. O

Convulsion O
following O
intravenous O
fluorescein B
angiography O
. O

Tonic O
- O
clonic O
seizures O
followed O
intravenous O
fluorescein B
injection O
for O
fundus O
angiography O
in O
a O
47 O
- O
year O
- O
old O
male O
. O

Despite O
precautions O
this O
adverse O
reaction O
recurred O
on O
re O
- O
exposure O
to O
intravenous O
fluorescein B
. O

Pharmacology O
of O
ACC B
- I
9653 I
( O
phenytoin B
prodrug O
) O
. O

ACC B
- I
9653 I
, O
the O
disodium B
phosphate I
ester I
of O
3 B
- I
hydroxymethyl I
- I
5 I
, I
5 I
- I
diphenylhydantoin I
, O
is O
a O
prodrug O
of O
phenytoin B
with O
advantageous O
physicochemical O
properties O
. O

ACC B
- I
9653 I
is O
rapidly O
converted O
enzymatically O
to O
phenytoin B
in O
vivo O
. O

ACC B
- I
9653 I
and O
phenytoin B
sodium I
have O
equivalent O
anticonvulsant O
activity O
against O
seizures O
induced O
by O
maximal O
electroshock O
( O
MES O
) O
in O
mice O
following O
i O
. O
p O
. O
, O
oral O
, O
or O
i O
. O
v O
. O
administration O
. O

The O
ED50 O
doses O
were O
16 O
mg O
/ O
kg O
for O
i O
. O
v O
. O
ACC B
- I
9653 I
and O
8 O
mg O
/ O
kg O
for O
i O
. O
v O
. O
phenytoin B
sodium I
. O

ACC B
- I
9653 I
and O
phenytoin B
sodium I
have O
similar O
antiarrhythmic O
activity O
against O
ouabain B
- O
induced O
ventricular O
tachycardia O
in O
anesthetized O
dogs O
. O

The O
total O
doses O
of O
ACC B
- I
9653 I
or O
phenytoin B
sodium I
necessary O
to O
convert O
the O
arrhythmia O
to O
a O
normal O
sinus O
rhythm O
were O
24 O
+ O
/ O
- O
6 O
and O
14 O
+ O
/ O
- O
3 O
mg O
/ O
kg O
, O
respectively O
. O

Only O
phenytoin B
sodium I
displayed O
in O
vitro O
antiarrhythmic O
activity O
against O
strophanthidin B
- O
induced O
arrhythmias O
in O
guinea O
pig O
right O
atria O
. O

In O
anesthetized O
dogs O
, O
a O
high O
dose O
of O
ACC B
- I
9653 I
( O
31 O
mg O
/ O
kg O
) O
was O
infused O
over O
15 O
, O
20 O
, O
and O
30 O
min O
and O
the O
responses O
were O
compared O
to O
an O
equimolar O
dose O
of O
phenytoin B
sodium I
( O
21 O
mg O
/ O
kg O
) O
. O

The O
ACC B
- I
9653 I
and O
phenytoin B
sodium I
treatments O
produced O
similar O
marked O
reductions O
in O
diastolic O
blood O
pressure O
and O
contractile O
force O
( O
LVdP O
/ O
dt O
) O
. O

The O
maximum O
effects O
of O
each O
treatment O
occurred O
at O
the O
time O
of O
maximum O
phenytoin B
sodium I
levels O
. O

Acute O
toxicity O
studies O
of O
ACC B
- I
9653 I
and O
phenytoin B
sodium I
were O
carried O
out O
in O
mice O
, O
rats O
, O
rabbits O
, O
and O
dogs O
by O
i O
. O
v O
. O
, O
i O
. O
m O
. O
, O
and O
i O
. O
p O
. O
routes O
of O
administration O
. O

The O
systemic O
toxic O
signs O
of O
both O
agents O
were O
similar O
and O
occurred O
at O
approximately O
equivalent O
doses O
. O

Importantly O
, O
the O
local O
irritation O
of O
ACC B
- I
9653 I
was O
markedly O
less O
than O
phenytoin B
sodium I
following O
i O
. O
m O
. O
administration O
. O
( O
ABSTRACT O
TRUNCATED O
AT O
250 O
WORDS O
) O

Tachyphylaxis O
to O
systemic O
but O
not O
to O
airway O
responses O
during O
prolonged O
therapy O
with O
high O
dose O
inhaled O
salbutamol B
in O
asthmatics O
. O

High O
doses O
of O
inhaled O
salbutamol B
produce O
substantial O
improvements O
in O
airway O
response O
in O
patients O
with O
asthma O
, O
and O
are O
associated O
with O
dose O
- O
dependent O
systemic O
beta O
- O
adrenoceptor O
responses O
. O

The O
purpose O
of O
the O
present O
study O
was O
to O
investigate O
whether O
tachyphylaxis O
occurs O
during O
prolonged O
treatment O
with O
high O
dose O
inhaled O
salbutamol B
. O

Twelve O
asthmatic O
patients O
( O
FEV1 O
, O
81 O
+ O
/ O
- O
4 O
% O
predicted O
) O
, O
requiring O
only O
occasional O
inhaled O
beta O
- O
agonists O
as O
their O
sole O
therapy O
, O
were O
given O
a O
14 O
- O
day O
treatment O
with O
high O
dose O
inhaled O
salbutamol B
( O
HDS O
) O
, O
4 O
, O
000 O
micrograms O
daily O
, O
low O
dose O
inhaled O
salbutamol B
( O
LDS O
) O
, O
800 O
micrograms O
daily O
, O
or O
placebo O
( O
PI O
) O
by O
metered O
- O
dose O
inhaler O
in O
a O
double O
- O
blind O
, O
randomized O
crossover O
design O
. O

During O
the O
14 O
- O
day O
run O
- O
in O
and O
during O
washout O
periods O
, O
inhaled O
beta O
- O
agonists O
were O
withheld O
and O
ipratropium B
bromide I
was O
substituted O
for O
rescue O
purposes O
. O

At O
the O
end O
of O
each O
14 O
- O
day O
treatment O
, O
a O
dose O
- O
response O
curve O
( O
DRC O
) O
was O
performed O
, O
and O
airway O
( O
FEV1 O
, O
FEF25 O
- O
75 O
) O
chronotropic O
( O
HR O
) O
, O
tremor O
, O
and O
metabolic O
( O
K B
, O
Glu B
) O
responses O
were O
measured O
at O
each O
step O
( O
from O
100 O
to O
4 O
, O
000 O
micrograms O
) O
. O

Treatment O
had O
no O
significant O
effect O
on O
baseline O
values O
. O

There O
were O
dose O
- O
dependent O
increases O
in O
FEV1 O
and O
FEF25 O
- O
75 O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
and O
pretreatment O
with O
HDS O
did O
not O
displace O
the O
DRC O
to O
the O
right O
. O

DRC O
for O
HR O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
K B
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
and O
Glu B
( O
p O
less O
than O
0 O
. O
005 O
) O
were O
attenuated O
after O
treatment O
with O
HDS O
compared O
with O
PI O
. O

There O
were O
also O
differences O
between O
HDS O
and O
LDS O
for O
HR O
( O
p O
less O
than O
0 O
. O
001 O
) O
and O
Glu B
( O
p O
less O
than O
0 O
. O
05 O
) O
responses O
. O

Frequency O
and O
severity O
of O
subjective O
adverse O
effects O
were O
also O
reduced O
after O
HDS O
: O
tremor O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
palpitations O
( O
p O
less O
than O
0 O
. O
001 O
) O
. O
( O
ABSTRACT O
TRUNCATED O
AT O
250 O
WORDS O
) O

Phenytoin B
induced O
fatal O
hepatic O
injury O
. O

A O
61 O
year O
old O
female O
developed O
fatal O
hepatic O
failure O
after O
phenytoin B
administration O
. O

A O
typical O
multisystem O
clinical O
pattern O
precedes O
the O
manifestations O
of O
hepatic O
injury O
. O

The O
hematologic O
, O
biochemical O
and O
pathologic O
features O
indicate O
a O
mixed O
hepatocellular O
damage O
due O
to O
drug O
hypersensitivity O
. O

In O
a O
patient O
receiving O
phenytoin B
who O
presents O
a O
viral O
- O
like O
illness O
, O
early O
recognition O
and O
discontinuation O
of O
the O
drug O
are O
mandatory O
. O

Treatment O
of O
lethal O
pertussis O
vaccine O
reaction O
with O
histamine B
H1 O
antagonists O
. O

We O
studied O
mortality O
after O
pertussis O
immunization O
in O
the O
mouse O
. O

Without O
treatment O
, O
73 O
of O
92 O
animals O
( O
80 O
% O
) O
died O
after O
injection O
of O
bovine O
serum O
albumin O
( O
BSA O
) O
on O
day O
+ O
7 O
of O
pertussis O
immunization O
. O

After O
pretreatment O
with O
3 O
mg O
of O
cyproheptadine B
, O
2 O
mg O
mianserin B
, O
or O
2 O
mg O
chlorpheniramine B
, O
only O
5 O
of O
105 O
animals O
( O
5 O
% O
) O
died O
after O
receiving O
BSA O
on O
day O
+ O
7 O
( O
p O
less O
than O
0 O
. O
001 O
) O
. O

Blockade O
of O
histamine B
H1 O
receptors O
may O
reduce O
mortality O
in O
pertussis O
immunization O
- O
induced O
encephalopathy O
in O
mice O
. O

Support O
for O
adrenaline B
- O
hypertension O
hypothesis O
: O
18 O
hour O
pressor O
effect O
after O
6 O
hours O
adrenaline B
infusion O
. O

In O
a O
double O
blind O
, O
crossover O
study O
6 O
h O
infusions O
of O
adrenaline B
( O
15 O
ng O
/ O
kg O
/ O
min O
; O
1 O
ng O
= O
5 O
. O
458 O
pmol O
) O
, O
noradrenaline B
( O
30 O
ng O
/ O
kg O
/ O
min O
; O
1 O
ng O
= O
5 O
. O
911 O
pmol O
) O
, O
and O
a O
5 O
% O
dextrose B
solution O
( O
5 O
. O
4 O
ml O
/ O
h O
) O
, O
were O
given O
to O
ten O
healthy O
volunteers O
in O
random O
order O
2 O
weeks O
apart O
. O

By O
means O
of O
intra O
- O
arterial O
ambulatory O
monitoring O
the O
haemodynamic O
effects O
were O
followed O
for O
18 O
h O
after O
the O
infusions O
were O
stopped O
. O

Adrenaline B
, O
but O
not O
noradrenaline B
, O
caused O
a O
delayed O
and O
protracted O
pressor O
effect O
. O

Over O
the O
total O
postinfusion O
period O
systolic O
and O
diastolic O
arterial O
pressure O
were O
6 O
( O
SEM O
2 O
) O
% O
and O
7 O
( O
2 O
) O
% O
, O
respectively O
, O
higher O
than O
after O
dextrose B
infusion O
( O
ANOVA O
, O
p O
less O
than O
0 O
. O
001 O
) O
. O

Thus O
, O
" O
stress O
" O
levels O
of O
adrenaline B
( O
230 O
pg O
/ O
ml O
) O
for O
6 O
h O
cause O
a O
delayed O
and O
protracted O
pressor O
effect O
. O

These O
findings O
are O
strong O
support O
for O
the O
adrenaline B
- O
hypertension O
hypothesis O
in O
man O
. O

Effect O
of O
alkylxanthines B
on O
gentamicin B
- O
induced O
acute O
renal O
failure O
in O
the O
rat O
. O

Adenosine B
antagonists O
have O
been O
previously O
shown O
to O
be O
of O
benefit O
in O
some O
ischaemic O
and O
nephrotoxic O
models O
of O
acute O
renal O
failure O
( O
ARF O
) O
. O

In O
the O
present O
study O
, O
the O
effects O
of O
three O
alkylxanthines B
with O
different O
potencies O
as O
adenosine B
antagonists O
8 B
- I
phenyltheophylline I
, O
theophylline B
and O
enprofylline B
, O
were O
examined O
in O
rats O
developing O
acute O
renal O
failure O
after O
4 O
daily O
injections O
of O
gentamicin B
( O
200 O
mg O
kg O
- O
1 O
) O
. O

Renal O
function O
was O
assessed O
by O
biochemical O
( O
plasma O
urea B
and O
creatinine B
) O
, O
functional O
( O
urine O
analysis O
and O
[ O
3H O
] O
inulin O
and O
[ O
14C O
] O
p B
- I
aminohippuric I
acid I
clearances O
) O
and O
morphological O
( O
degree O
of O
necrosis O
) O
indices O
. O

The O
various O
drug O
treatments O
produced O
improvements O
in O
some O
, O
but O
not O
all O
, O
measurements O
of O
renal O
function O
. O

However O
, O
any O
improvement O
produced O
by O
drug O
treatment O
was O
largely O
a O
result O
of O
a O
beneficial O
effect O
exerted O
by O
its O
vehicle O
( O
polyethylene B
glycol I
and O
NaOH B
) O
. O

The O
lack O
of O
any O
consistent O
protective O
effect O
noted O
with O
the O
alkylxanthines B
tested O
in O
the O
present O
study O
indicates O
that O
adenosine B
plays O
little O
, O
if O
any O
, O
pathophysiological O
role O
in O
gentamicin B
- O
induced O
ARF O
. O

Adverse O
ocular O
reactions O
possibly O
associated O
with O
isotretinoin B
. O

A O
total O
of O
261 O
adverse O
ocular O
reactions O
occurred O
in O
237 O
patients O
who O
received O
isotretinoin B
, O
a O
commonly O
used O
drug O
in O
the O
treatment O
of O
severe O
cystic O
acne O
. O

Blepharoconjunctivitis O
, O
subjective O
complaints O
of O
dry O
eyes O
, O
blurred O
vision O
, O
contact O
lens O
intolerance O
, O
and O
photodermatitis O
are O
reversible O
side O
effects O
. O

More O
serious O
ocular O
adverse O
reactions O
include O
papilledema O
, O
pseudotumor O
cerebri O
, O
and O
white O
or O
gray O
subepithelial O
corneal O
opacities O
; O
all O
of O
these O
are O
reversible O
if O
the O
drug O
is O
discontinued O
. O

Reported O
cases O
of O
decreased O
dark O
adaptation O
are O
under O
investigation O
. O

Isotretinoin B
is O
contraindicated O
in O
pregnancy O
because O
of O
the O
many O
reported O
congenital O
abnormalities O
after O
maternal O
use O
( O
including O
microphthalmos O
, O
orbital O
hypertelorism O
, O
and O
optic O
nerve O
hypoplasia O
) O
. O

Procaterol B
and O
terbutaline B
in O
bronchial O
asthma O
. O

A O
double O
- O
blind O
, O
placebo O
- O
controlled O
, O
cross O
- O
over O
study O
. O

Procaterol B
, O
a O
new O
beta O
- O
2 O
adrenoceptor O
stimulant O
, O
was O
studied O
in O
a O
double O
- O
blind O
, O
placebo O
- O
controlled O
, O
cross O
- O
over O
trial O
in O
patients O
with O
bronchial O
asthma O
. O

Oral O
procaterol B
50 O
micrograms O
b O
. O
d O
. O
, O
procaterol B
100 O
micrograms O
b O
. O
d O
. O
, O
and O
terbutaline B
5 O
mg O
t O
. O
i O
. O
d O
. O
, O
were O
compared O
when O
given O
randomly O
in O
1 O
- O
week O
treatment O
periods O
. O

The O
best O
clinical O
effect O
was O
found O
with O
terbutaline B
. O

Both O
anti O
- O
asthmatic O
and O
tremorgenic O
effects O
of O
procaterol B
were O
dose O
- O
related O
. O

Procaterol B
appeared O
effective O
in O
the O
doses O
tested O
, O
and O
a O
twice O
daily O
regimen O
would O
appear O
to O
be O
suitable O
with O
this O
drug O
. O

Subacute O
effects O
of O
propranolol B
and O
B B
24 I
/ I
76 I
on O
isoproterenol B
- O
induced O
rat O
heart O
hypertrophy O
in O
correlation O
with O
blood O
pressure O
. O

We O
compared O
the O
potential O
beta O
- O
receptor O
blocker O
, O
B B
24 I
/ I
76 I
i O
. O
e O
. O
1 B
- I
( I
2 I
, I
4 I
- I
dichlorophenoxy I
) I
- I
3 I
[ I
2 I
- I
3 I
, I
4 I
- I
dimethoxyphenyl I
) I
ethanolamino I
] I
- I
prop I
an I
- I
2 I
- I
ol I
, O
which O
is O
characterized O
by O
beta O
1 O
- O
adrenoceptor O
blocking O
and O
beta O
2 O
- O
adrenoceptor O
stimulating O
properties O
with O
propranolol B
. O

The O
studies O
were O
performed O
using O
an O
experimental O
model O
of O
isoproterenol B
- O
induced O
heart O
hypertrophy O
in O
rats O
. O

A O
correlation O
of O
the O
blood O
pressure O
was O
neither O
found O
in O
the O
development O
nor O
in O
the O
attempt O
to O
suppress O
the O
development O
of O
heart O
hypertrophy O
with O
the O
two O
beta O
- O
receptor O
blockers O
. O

Both O
beta O
- O
blockers O
influenced O
the O
development O
of O
hypertrophy O
to O
a O
different O
, O
but O
not O
reproducible O
extent O
. O

It O
was O
possible O
to O
suppress O
the O
increased O
ornithine B
decarboxylase O
activity O
with O
both O
beta O
- O
blockers O
in O
hypertrophied O
hearts O
, O
but O
there O
was O
no O
effect O
on O
the O
heart O
mass O
. O

Neither O
propranolol B
nor O
B B
24 I
/ I
76 I
could O
stop O
the O
changes O
in O
the O
characteristic O
myosin O
isoenzyme O
pattern O
of O
the O
hypertrophied O
rat O
heart O
. O

Thus O
, O
the O
investigations O
did O
not O
provide O
any O
evidence O
that O
the O
beta O
- O
receptor O
blockers O
propranolol B
and O
B B
24 I
/ I
76 I
have O
the O
potency O
to O
prevent O
isoproterenol B
from O
producing O
heart O
hypertrophy O
. O

Increased O
anxiogenic O
effects O
of O
caffeine B
in O
panic O
disorders O
. O

The O
effects O
of O
oral O
administration O
of O
caffeine B
( O
10 O
mg O
/ O
kg O
) O
on O
behavioral O
ratings O
, O
somatic O
symptoms O
, O
blood O
pressure O
and O
plasma O
levels O
of O
3 B
- I
methoxy I
- I
4 I
- I
hydroxyphenethyleneglycol I
( O
MHPG B
) O
and O
cortisol B
were O
determined O
in O
17 O
healthy O
subjects O
and O
21 O
patients O
meeting O
DSM O
- O
III O
criteria O
for O
agoraphobia O
with O
panic O
attacks O
or O
panic O
disorder O
. O

Caffeine B
produced O
significantly O
greater O
increases O
in O
subject O
- O
rated O
anxiety O
, O
nervousness O
, O
fear O
, O
nausea O
, O
palpitations O
, O
restlessness O
, O
and O
tremors O
in O
the O
patients O
compared O
with O
healthy O
subjects O
. O

In O
the O
patients O
, O
but O
not O
the O
healthy O
subjects O
, O
these O
symptoms O
were O
significantly O
correlated O
with O
plasma O
caffeine B
levels O
. O

Seventy O
- O
one O
percent O
of O
the O
patients O
reported O
that O
the O
behavioral O
effects O
of O
caffeine B
were O
similar O
to O
those O
experienced O
during O
panic O
attacks O
. O

Caffeine B
did O
not O
alter O
plasma O
MHPG O
levels O
in O
either O
the O
healthy O
subjects O
or O
patients O
. O

Caffeine B
increased O
plasma O
cortisol B
levels O
equally O
in O
the O
patient O
and O
healthy O
groups O
. O

Because O
caffeine B
is O
an O
adenosine B
receptor O
antagonist O
, O
these O
results O
suggest O
that O
some O
panic O
disorder O
patients O
may O
have O
abnormalities O
in O
neuronal O
systems O
involving O
adenosine B
. O

Patients O
with O
anxiety O
disorders O
may O
benefit O
by O
avoiding O
caffeine B
- O
containing O
foods O
and O
beverages O
. O

Comparison O
of O
the O
effect O
of O
oxitropium B
bromide I
and O
of O
slow O
- O
release O
theophylline B
on O
nocturnal O
asthma O
. O

The O
effects O
of O
a O
new O
inhaled O
antimuscarinic O
drug O
, O
oxitropium B
bromide I
, O
and O
of O
a O
slow O
- O
release O
theophylline B
preparation O
upon O
nocturnal O
asthma O
were O
compared O
in O
a O
placebo O
- O
controlled O
double O
- O
blind O
study O
. O

Two O
samples O
were O
studied O
: O
12 O
patients O
received O
oxitropium B
at O
600 O
micrograms O
( O
6 O
subjects O
) O
or O
at O
400 O
micrograms O
t O
. O
i O
. O
d O
. O

( O
6 O
subjects O
) O
whereas O
11 O
received O
theophylline B
at O
300 O
mg O
b O
. O
i O
. O
d O
. O

Morning O
dipping O
, O
assessed O
by O
the O
fall O
in O
peak O
flow O
overnight O
, O
was O
significantly O
reduced O
in O
the O
periods O
when O
either O
active O
drug O
was O
taken O
, O
whereas O
no O
difference O
was O
noticed O
during O
the O
placebo O
administration O
. O

No O
significant O
difference O
was O
noticed O
between O
results O
obtained O
with O
either O
active O
drug O
, O
as O
well O
as O
with O
either O
dosage O
of O
oxitropium B
. O

No O
subject O
reported O
side O
effects O
of O
oxitropium B
, O
as O
compared O
to O
three O
subjects O
reporting O
nausea O
, O
vomiting O
and O
tremors O
after O
theophylline B
. O

Oxitropium B
proves O
to O
be O
a O
valuable O
alternative O
to O
theophylline B
in O
nocturnal O
asthma O
, O
since O
it O
is O
equally O
potent O
, O
safer O
and O
does O
not O
require O
the O
titration O
of O
dosage O
. O

Penicillin B
anaphylaxis O
. O

A O
case O
of O
oral O
penicillin B
anaphylaxis O
is O
described O
, O
and O
the O
terminology O
, O
occurrence O
, O
clinical O
manifestations O
, O
pathogenesis O
, O
prevention O
, O
and O
treatment O
of O
anaphylaxis O
are O
reviewed O
. O

Emergency O
physicians O
should O
be O
aware O
of O
oral O
penicillin B
anaphylaxis O
in O
order O
to O
prevent O
its O
occurrence O
by O
prescribing O
the O
antibiotic O
judiciously O
and O
knowledgeably O
and O
to O
offer O
optimal O
medical O
therapy O
once O
this O
life O
- O
threatening O
reaction O
has O
begun O
. O

Reversible O
valproic B
acid I
- O
induced O
dementia O
: O
a O
case O
report O
. O

Reversible O
valproic B
acid I
- O
induced O
dementia O
was O
documented O
in O
a O
21 O
- O
year O
- O
old O
man O
with O
epilepsy O
who O
had O
a O
3 O
- O
year O
history O
of O
insidious O
progressive O
decline O
in O
global O
cognitive O
abilities O
documented O
by O
serial O
neuropsychological O
studies O
. O

Repeat O
neuropsychological O
testing O
7 O
weeks O
after O
discontinuation O
of O
the O
drug O
revealed O
dramatic O
improvement O
in O
IQ O
, O
memory O
, O
naming O
, O
and O
other O
tasks O
commensurate O
with O
clinical O
recovery O
in O
his O
intellectual O
capacity O
. O

Possible O
pathophysiological O
mechanisms O
which O
may O
have O
been O
operative O
in O
this O
case O
include O
: O
a O
direct O
central O
nervous O
system O
( O
CNS O
) O
toxic O
effect O
of O
valproic B
acid I
; O
a O
paradoxical O
epileptogenic O
effect O
secondary O
to O
the O
drug O
; O
and O
an O
indirect O
CNS O
toxic O
effect O
mediated O
through O
valproic B
acid I
- O
induced O
hyperammonemia O
. O

Reversal O
of O
scopolamine B
- O
induced O
amnesia O
of O
passive O
avoidance O
by O
pre O
- O
and O
post O
- O
training O
naloxone B
. O

In O
a O
series O
of O
five O
experiments O
, O
the O
modulating O
role O
of O
naloxone B
on O
a O
scopolamine B
- O
induced O
retention O
deficit O
in O
a O
passive O
avoidance O
paradigm O
was O
investigated O
in O
mice O
. O

Scopolamine B
, O
but O
not O
methyl B
scopolamine I
( O
1 O
and O
3 O
mg O
/ O
kg O
) O
, O
induced O
an O
amnesia O
as O
measured O
by O
latency O
and O
duration O
parameters O
. O

Naloxone B
( O
0 O
. O
3 O
, O
1 O
, O
3 O
, O
and O
10 O
mg O
/ O
kg O
) O
injected O
prior O
to O
training O
attenuated O
the O
retention O
deficit O
with O
a O
peak O
of O
activity O
at O
3 O
mg O
/ O
kg O
. O

The O
effect O
of O
naloxone B
could O
be O
antagonized O
with O
morphine B
( O
1 O
, O
3 O
, O
and O
10 O
mg O
/ O
kg O
) O
, O
demonstrating O
the O
opioid O
specificity O
of O
the O
naloxone B
effect O
. O

Post O
- O
training O
administration O
of O
naloxone B
( O
3 O
mg O
/ O
kg O
) O
as O
a O
single O
or O
as O
a O
split O
dose O
also O
attenuated O
the O
scopolamine B
- O
induced O
amnesia O
. O

Control O
experiments O
indicated O
that O
neither O
an O
increase O
in O
pain O
sensitivity O
( O
pre O
- O
training O
naloxone B
) O
nor O
an O
induced O
aversive O
state O
( O
post O
- O
training O
naloxone B
) O
appear O
to O
be O
responsible O
for O
the O
influence O
of O
naloxone B
on O
the O
scopolamine B
- O
induced O
retention O
deficit O
. O

These O
results O
extend O
previous O
findings O
implicating O
a O
cholinergic O
- O
opioid O
interaction O
in O
memory O
processes O
. O

A O
possible O
mechanism O
for O
this O
interaction O
involving O
the O
septo O
- O
hippocampal O
cholinergic O
pathway O
is O
discussed O
. O

Electron O
microscopic O
investigations O
of O
the O
cyclophosphamide B
- O
induced O
lesions O
of O
the O
urinary O
bladder O
of O
the O
rat O
and O
their O
prevention O
by O
mesna B
. O

Fully O
developed O
cyclophosphamide B
- O
induced O
cystitis O
is O
characterized O
by O
nearly O
complete O
detachment O
of O
the O
urothelium O
, O
severe O
submucosal O
edema O
owing O
to O
damage O
to O
the O
microvascular O
bed O
and O
focal O
muscle O
necroses O
. O

The O
initial O
response O
to O
the O
primary O
attack O
by O
the O
cyclophosphamide B
metabolites O
seems O
to O
be O
fragmentation O
of O
the O
luminal B
membrane O
. O

This O
damages O
the O
cellular O
barrier O
against O
the O
hypertonic O
urine O
. O

Subsequent O
breaks O
in O
the O
lateral O
cell O
membranes O
of O
the O
superficial O
cells O
and O
in O
all O
the O
plasma O
membranes O
of O
the O
intermediate O
and O
basal O
cells O
, O
intercellular O
and O
intracellular O
edema O
and O
disintegration O
of O
the O
desmosomes O
and O
hemidesmosomes O
lead O
to O
progressive O
degeneration O
and O
detachment O
of O
the O
epithelial O
cells O
with O
exposure O
and O
splitting O
of O
the O
basal O
membrane O
. O

The O
morphological O
changes O
of O
the O
endothelial O
cells O
, O
which O
become O
more O
pronounced O
in O
the O
later O
stages O
of O
the O
experiment O
, O
the O
involvement O
of O
blood O
vessels O
regardless O
of O
their O
diameter O
and O
the O
location O
- O
dependent O
extent O
of O
the O
damage O
indicate O
a O
direct O
type O
of O
damage O
which O
is O
preceded O
by O
a O
mediator O
- O
induced O
increase O
in O
permeability O
, O
the O
morphological O
correlate O
of O
which O
is O
the O
formation O
of O
gaps O
in O
the O
interendothelial O
cell O
connections O
on O
the O
venules O
. O

These O
changes O
can O
be O
effectively O
prevented O
by O
mesna B
. O

The O
only O
sign O
of O
a O
possible O
involvement O
is O
the O
increase O
in O
the O
number O
of O
specific O
granules O
with O
a O
presumed O
lysosomal O
function O
in O
the O
superficial O
cells O
. O

Increase O
in O
intragastric O
pressure O
during O
suxamethonium B
- O
induced O
muscle O
fasciculations O
in O
children O
: O
inhibition O
by O
alfentanil B
. O

Changes O
in O
intragastric O
pressure O
after O
the O
administration O
of O
suxamethonium B
1 O
. O
5 O
mg O
kg O
- O
1 O
i O
. O
v O
. O
were O
studied O
in O
32 O
children O
( O
mean O
age O
6 O
. O
9 O
yr O
) O
pretreated O
with O
either O
physiological O
saline O
or O
alfentanil B
50 O
micrograms O
kg O
- O
1 O
. O

Anaesthesia O
was O
induced O
with O
thiopentone B
5 O
mg O
kg O
- O
1 O
. O

The O
incidence O
and O
intensity O
of O
muscle O
fasciculations O
caused O
by O
suxamethonium B
were O
significantly O
greater O
in O
the O
control O
than O
in O
the O
alfentanil B
group O
. O

The O
intragastric O
pressure O
during O
muscle O
fasciculations O
was O
significantly O
higher O
in O
the O
control O
group O
( O
16 O
+ O
/ O
- O
0 O
. O
7 O
( O
SEM O
) O
cm O
H2O B
) O
than O
in O
the O
alfentanil B
group O
( O
7 O
. O
7 O
+ O
/ O
- O
1 O
. O
5 O
( O
SEM O
) O
cm O
H2O B
) O
. O

The O
increase O
in O
intragastric O
pressure O
was O
directly O
related O
to O
the O
intensity O
of O
muscle O
fasciculations O
( O
regression O
line O
: O
y O
= O
0 O
. O
5 O
+ O
4 O
. O
78x O
with O
r O
of O
0 O
. O
78 O
) O
. O

It O
is O
concluded O
that O
intragastric O
pressure O
increases O
significantly O
during O
muscle O
fasciculations O
caused O
by O
suxamethonium B
in O
healthy O
children O
. O

Alfentanil B
50 O
micrograms O
kg O
- O
1 O
effectively O
inhibits O
the O
incidence O
and O
intensity O
of O
suxamethonium B
- O
induced O
muscle O
fasciculations O
; O
moreover O
, O
intragastric O
pressure O
remains O
at O
its O
control O
value O
. O

Acute O
insulin O
treatment O
normalizes O
the O
resistance O
to O
the O
cardiotoxic O
effect O
of O
isoproterenol B
in O
streptozotocin B
diabetic O
rats O
. O

A O
morphometric O
study O
of O
isoproterenol B
induced O
myocardial O
fibrosis O
. O

The O
acute O
effect O
of O
insulin O
treatment O
on O
the O
earlier O
reported O
protective O
effect O
of O
streptozotocin B
diabetes O
against O
the O
cardiotoxic O
effect O
of O
high O
doses O
of O
isoproterenol B
( O
ISO B
) O
was O
investigated O
in O
rats O
. O

Thirty O
to O
135 O
min O
after O
the O
injection O
of O
crystalline O
insulin O
, O
ISO B
was O
given O
subcutaneously O
and O
when O
ISO B
induced O
fibrosis O
in O
the O
myocardium O
was O
morphometrically O
analyzed O
7 O
days O
later O
, O
a O
highly O
significant O
correlation O
( O
r O
= O
0 O
. O
83 O
, O
2 O
p O
= O
0 O
. O
006 O
) O
to O
the O
slope O
of O
the O
fall O
in O
blood O
glucose B
after O
insulin O
treatment O
appeared O
. O

The O
myocardial O
content O
of O
catecholamines B
was O
estimated O
in O
these O
8 O
day O
diabetic O
rats O
. O

The O
norepinephrine B
content O
was O
significantly O
increased O
while O
epinephrine B
remained O
unchanged O
. O

An O
enhanced O
sympathetic O
nervous O
system O
activity O
with O
a O
consequent O
down O
regulation O
of O
the O
myocardial O
beta O
- O
adrenergic O
receptors O
could O
, O
therefore O
, O
explain O
this O
catecholamine B
resistance O
. O

The O
rapid O
reversion O
after O
insulin O
treatment O
excludes O
the O
possibility O
that O
streptozotocin B
in O
itself O
causes O
the O
ISO B
resistance O
and O
points O
towards O
a O
direct O
insulin O
effect O
on O
myocardial O
catecholamine B
sensitivity O
in O
diabetic O
rats O
. O

The O
phenomenon O
described O
might O
elucidate O
pathogenetic O
mechanisms O
behind O
toxic O
myocardial O
cell O
degeneration O
and O
may O
possibly O
have O
relevance O
for O
acute O
cardiovascular O
complications O
in O
diabetic O
patients O
. O

Differential O
effects O
of O
non O
- O
steroidal O
anti O
- O
inflammatory O
drugs O
on O
seizures O
produced O
by O
pilocarpine B
in O
rats O
. O

The O
muscarinic O
cholinergic O
agonist O
pilocarpine B
induces O
in O
rats O
seizures O
and O
status O
epilepticus O
followed O
by O
widespread O
damage O
to O
the O
forebrain O
. O

The O
present O
study O
was O
designed O
to O
investigate O
the O
effect O
of O
5 O
non O
- O
steroidal O
anti O
- O
inflammatory O
drugs O
, O
sodium B
salicylate I
, O
phenylbutazone B
, O
indomethacin B
, O
ibuprofen B
and O
mefenamic B
acid I
, O
on O
seizures O
produced O
by O
pilocarpine B
. O

Pretreatment O
of O
rats O
with O
sodium B
salicylate I
, O
ED50 O
103 O
mg O
/ O
kg O
( O
60 O
- O
174 O
) O
, O
and O
phenylbutazone B
, O
59 O
mg O
/ O
kg O
( O
50 O
- O
70 O
) O
converted O
the O
non O
- O
convulsant O
dose O
of O
pilocarpine B
, O
200 O
mg O
/ O
kg O
, O
to O
a O
convulsant O
one O
. O

Indomethacin B
, O
1 O
- O
10 O
mg O
/ O
kg O
, O
and O
ibuprofen B
, O
10 O
- O
100 O
mg O
/ O
kg O
, O
failed O
to O
modulate O
seizures O
produced O
by O
pilocarpine B
. O

Mefenamic B
acid I
, O
26 O
( O
22 O
- O
30 O
) O
mg O
/ O
kg O
, O
prevented O
seizures O
and O
protected O
rats O
from O
seizure O
- O
related O
brain O
damage O
induced O
by O
pilocarpine B
, O
380 O
mg O
/ O
kg O
. O

These O
results O
indicate O
that O
non O
- O
steroidal O
anti O
- O
inflammatory O
drugs O
differentially O
modulate O
the O
threshold O
for O
pilocarpine B
- O
induced O
seizures O
. O

Acute O
neurologic O
dysfunction O
after O
high O
- O
dose O
etoposide B
therapy O
for O
malignant O
glioma O
. O

Etoposide B
( O
VP B
- I
16 I
- I
213 I
) O
has O
been O
used O
in O
the O
treatment O
of O
many O
solid O
tumors O
and O
hematologic O
malignancies O
. O

When O
used O
in O
high O
doses O
and O
in O
conjunction O
with O
autologous O
bone O
marrow O
transplantation O
, O
this O
agent O
has O
activity O
against O
several O
treatment O
- O
resistant O
cancers O
including O
malignant O
glioma O
. O

In O
six O
of O
eight O
patients O
( O
75 O
% O
) O
who O
we O
treated O
for O
recurrent O
or O
resistant O
glioma O
, O
sudden O
severe O
neurologic O
deterioration O
occurred O
. O

This O
developed O
a O
median O
of O
9 O
days O
after O
initiation O
of O
high O
- O
dose O
etoposide B
therapy O
. O

Significant O
clinical O
manifestations O
have O
included O
confusion O
, O
papilledema O
, O
somnolence O
, O
exacerbation O
of O
motor O
deficits O
, O
and O
sharp O
increase O
in O
seizure O
activity O
. O

These O
abnormalities O
resolved O
rapidly O
after O
initiation O
of O
high O
- O
dose O
intravenous O
dexamethasone B
therapy O
. O

In O
all O
patients O
, O
computerized O
tomographic O
( O
CT O
) O
brain O
scans O
demonstrated O
stability O
in O
tumor O
size O
and O
peritumor O
edema O
when O
compared O
with O
pretransplant O
scans O
. O

This O
complication O
appears O
to O
represent O
a O
significant O
new O
toxicity O
of O
high O
- O
dose O
etoposide B
therapy O
for O
malignant O
glioma O
. O

Progressive O
bile O
duct O
injury O
after O
thiabendazole B
administration O
. O

A O
27 O
- O
yr O
- O
old O
man O
developed O
jaundice O
2 O
wk O
after O
exposure O
to O
thiabendazole B
. O

Cholestasis O
persisted O
for O
3 O
yr O
, O
at O
which O
time O
a O
liver O
transplant O
was O
performed O
. O

Two O
liver O
biopsy O
specimens O
and O
the O
hepatectomy O
specimen O
were O
remarkable O
for O
almost O
complete O
disappearance O
of O
interlobular O
bile O
ducts O
. O

Prominent O
fibrosis O
and O
hepatocellular O
regeneration O
were O
also O
present O
; O
however O
, O
the O
lobular O
architecture O
was O
preserved O
. O

This O
case O
represents O
an O
example O
of O
" O
idiosyncratic O
" O
drug O
- O
induced O
liver O
damage O
in O
which O
the O
primary O
target O
of O
injury O
is O
the O
bile O
duct O
. O

An O
autoimmune O
pathogenesis O
of O
the O
bile O
duct O
destruction O
is O
suggested O
. O

Differential O
effects O
of O
1 B
, I
4 I
- I
dihydropyridine I
calcium B
channel O
blockers O
: O
therapeutic O
implications O
. O

Increasing O
recognition O
of O
the O
importance O
of O
calcium B
in O
the O
pathogenesis O
of O
cardiovascular O
disease O
has O
stimulated O
research O
into O
the O
use O
of O
calcium B
channel O
blocking O
agents O
for O
treatment O
of O
a O
variety O
of O
cardiovascular O
diseases O
. O

The O
favorable O
efficacy O
and O
tolerability O
profiles O
of O
these O
agents O
make O
them O
attractive O
therapeutic O
modalities O
. O

Clinical O
applications O
of O
calcium B
channel O
blockers O
parallel O
their O
tissue O
selectivity O
. O

In O
contrast O
to O
verapamil B
and O
diltiazem B
, O
which O
are O
roughly O
equipotent O
in O
their O
actions O
on O
the O
heart O
and O
vascular O
smooth O
muscle O
, O
the O
dihydropyridine B
calcium B
channel O
blockers O
are O
a O
group O
of O
potent O
peripheral O
vasodilator O
agents O
that O
exert O
minimal O
electrophysiologic O
effects O
on O
cardiac O
nodal O
or O
conduction O
tissue O
. O

As O
the O
first O
dihydropyridine B
available O
for O
use O
in O
the O
United O
States O
, O
nifedipine B
controls O
angina O
and O
hypertension O
with O
minimal O
depression O
of O
cardiac O
function O
. O

Additional O
members O
of O
this O
group O
of O
calcium B
channel O
blockers O
have O
been O
studied O
for O
a O
variety O
of O
indications O
for O
which O
they O
may O
offer O
advantages O
over O
current O
therapy O
. O

Once O
or O
twice O
daily O
dosage O
possible O
with O
nitrendipine B
and O
nisoldipine B
offers O
a O
convenient O
administration O
schedule O
, O
which O
encourages O
patient O
compliance O
in O
long O
- O
term O
therapy O
of O
hypertension O
. O

The O
coronary O
vasodilating O
properties O
of O
nisoldipine B
have O
led O
to O
the O
investigation O
of O
this O
agent O
for O
use O
in O
angina O
. O

Selectivity O
for O
the O
cerebrovascular O
bed O
makes O
nimodipine B
potentially O
useful O
in O
the O
treatment O
of O
subarachnoid O
hemorrhage O
, O
migraine O
headache O
, O
dementia O
, O
and O
stroke O
. O

In O
general O
, O
the O
dihydropyridine B
calcium B
channel O
blockers O
are O
usually O
well O
tolerated O
, O
with O
headache O
, O
facial O
flushing O
, O
palpitations O
, O
edema O
, O
nausea O
, O
anorexia O
, O
and O
dizziness O
being O
the O
more O
common O
adverse O
effects O
. O

The O
enhancement O
of O
aminonucleoside B
nephrosis O
by O
the O
co O
- O
administration O
of O
protamine B
. O

An O
experimental O
model O
of O
focal O
segmental O
glomerular O
sclerosis O
( O
FSGS O
) O
was O
developed O
in O
rats O
by O
the O
combined O
administration O
of O
puromycin B
- I
aminonucleoside I
( O
AMNS B
) O
and O
protamine B
sulfate I
( O
PS B
) O
. O

Male O
Sprague O
- O
Dawley O
rats O
, O
uninephrectomized O
three O
weeks O
before O
, O
received O
daily O
injections O
of O
subcutaneous O
AMNS B
( O
1 O
mg O
/ O
100 O
g O
body O
wt O
) O
and O
intravenous O
PS O
( O
2 O
separated O
doses O
of O
2 O
. O
5 O
mg O
/ O
100 O
g O
body O
wt O
) O
for O
four O
days O
. O

The O
series O
of O
injections O
were O
repeated O
another O
three O
times O
at O
10 O
day O
intervals O
. O

The O
animals O
were O
sacrificed O
on O
days O
24 O
, O
52 O
, O
and O
80 O
. O

They O
developed O
nephrotic O
syndrome O
and O
finally O
renal O
failure O
. O

The O
time O
- O
course O
curve O
of O
creatinine B
clearance O
dropped O
and O
showed O
significant O
difference O
( O
P O
less O
than O
0 O
. O
01 O
) O
from O
that O
of O
each O
control O
group O
, O
such O
as O
, O
AMNS B
alone O
, O
PS O
alone O
or O
saline O
injected O
. O

Their O
glomeruli O
showed O
changes O
of O
progressive O
FSGS O
. O

The O
ultrastructural O
studies O
in O
the O
initial O
stage O
revealed O
significant O
lack O
of O
particles O
of O
perfused O
ruthenium B
red I
on O
the O
lamina O
rara O
externa O
and O
marked O
changes O
in O
epithelial O
cell O
cytoplasm O
. O

Therefore O
, O
it O
is O
suggested O
that O
the O
administration O
of O
PS B
enhances O
the O
toxicity O
of O
AMNS B
on O
the O
glomerulus O
and O
readily O
produces O
progressive O
FSGS O
in O
rats O
resulting O
in O
the O
end O
- O
stage O
renal O
disease O
. O

Theophylline B
neurotoxicity O
in O
pregnant O
rats O
. O

The O
purpose O
of O
this O
investigation O
was O
to O
determine O
whether O
the O
neurotoxicity O
of O
theophylline B
is O
altered O
in O
advanced O
pregnancy O
. O

Sprague O
- O
Dawley O
rats O
that O
were O
20 O
days O
pregnant O
and O
nonpregnant O
rats O
of O
the O
same O
age O
and O
strain O
received O
infusions O
of O
aminophylline B
until O
onset O
of O
maximal O
seizures O
which O
occurred O
after O
28 O
and O
30 O
minutes O
respectively O
. O

Theophylline B
concentrations O
at O
this O
endpoint O
in O
serum O
( O
total O
) O
and O
CSF O
were O
similar O
but O
serum O
( O
free O
) O
and O
brain O
concentrations O
were O
slightly O
different O
in O
pregnant O
rats O
. O

Theophylline B
serum O
protein O
binding O
determined O
by O
equilibrium O
dialysis O
was O
lower O
in O
pregnant O
rats O
. O

Fetal O
serum O
concentrations O
at O
onset O
of O
seizures O
in O
the O
mother O
were O
similar O
to O
maternal O
brain O
and O
CSF O
concentrations O
and O
correlated O
significantly O
with O
the O
former O
. O

It O
is O
concluded O
that O
advanced O
pregnancy O
has O
a O
negligible O
effect O
on O
the O
neurotoxic O
response O
to O
theophylline B
in O
rats O
. O

Hyperkalemia O
induced O
by O
indomethacin B
and O
naproxen B
and O
reversed O
by O
fludrocortisone B
. O

We O
have O
described O
a O
patient O
with O
severe O
rheumatoid O
arthritis O
and O
a O
history O
of O
mefenamic B
acid I
nephropathy O
in O
whom O
hyperkalemia O
and O
inappropriate O
hypoaldosteronism O
were O
caused O
by O
both O
indomethacin B
and O
naproxen B
, O
without O
major O
decline O
in O
renal O
function O
. O

It O
is O
likely O
that O
preexisting O
renal O
disease O
predisposed O
this O
patient O
to O
type O
IV O
renal O
tubular O
acidosis O
with O
prostaglandin B
synthetase O
inhibitors O
. O

Because O
he O
was O
unable O
to O
discontinue O
nonsteroidal O
anti O
- O
inflammatory O
drug O
therapy O
, O
fludrocortisone B
was O
added O
, O
correcting O
the O
hyperkalemia O
and O
allowing O
indomethacin B
therapy O
to O
be O
continued O
safely O
. O

Hypotension O
as O
a O
manifestation O
of O
cardiotoxicity O
in O
three O
patients O
receiving O
cisplatin B
and O
5 B
- I
fluorouracil I
. O

Cardiac O
symptoms O
, O
including O
hypotension O
, O
developed O
in O
three O
patients O
with O
advanced O
colorectal O
carcinoma O
while O
being O
treated O
with O
cisplatin B
( O
CDDP B
) O
and O
5 B
- I
fluorouracil I
( O
5 B
- I
FU I
) O
. O

In O
two O
patients O
, O
hypotension O
was O
associated O
with O
severe O
left O
ventricular O
dysfunction O
. O

All O
three O
patients O
required O
therapy O
discontinuation O
. O

Cardiac O
enzymes O
remained O
normal O
despite O
transient O
electrocardiographic O
( O
EKG O
) O
changes O
. O

The O
presentation O
and O
cardiac O
evaluation O
( O
hemodynamic O
, O
echocardiographic O
, O
and O
scintigraphic O
) O
of O
these O
patients O
suggest O
new O
manifestations O
of O
5 B
- I
FU I
cardiotoxicity O
that O
may O
be O
influenced O
by O
CDDP B
. O

The O
possible O
pathophysiologic O
mechanisms O
are O
discussed O
. O

Fatal O
aplastic O
anemia O
in O
a O
patient O
treated O
with O
carbamazepine B
. O

A O
case O
of O
fatal O
aplastic O
anemia O
due O
to O
carbamazepine B
treatment O
in O
an O
epileptic O
woman O
is O
reported O
. O

Despite O
concerns O
of O
fatal O
bone O
marrow O
toxicity O
due O
to O
carbamazepine B
, O
this O
is O
only O
the O
fourth O
documented O
and O
published O
report O
. O

Carbamazepine B
is O
a O
safe O
drug O
, O
but O
physicians O
and O
patients O
should O
be O
aware O
of O
the O
exceedingly O
rare O
but O
potentially O
fatal O
side O
effects O
, O
better O
prevented O
by O
clinical O
than O
by O
laboratory O
monitoring O
. O

Participation O
of O
a O
bulbospinal O
serotonergic O
pathway O
in O
the O
rat O
brain O
in O
clonidine B
- O
induced O
hypotension O
and O
bradycardia O
. O

The O
effects O
of O
microinjection O
of O
clonidine B
( O
1 O
- O
10 O
micrograms O
in O
1 O
microliter O
) O
into O
a O
region O
adjacent O
to O
the O
ventrolateral O
surface O
of O
the O
medulla O
oblongata O
on O
cardiovascular O
function O
were O
assessed O
in O
urethane B
- O
anesthetized O
rats O
. O

Intramedullary O
administration O
of O
clonidine B
, O
but O
not O
saline O
vehicle O
, O
caused O
a O
dose O
- O
dependent O
decrease O
in O
both O
the O
mean O
arterial O
pressure O
and O
the O
heart O
rate O
. O

The O
clonidine B
- O
induced O
hypotension O
was O
antagonized O
by O
prior O
spinal O
transection O
, O
but O
not O
bilateral O
vagotomy O
. O

On O
the O
other O
hand O
, O
the O
clonidine B
- O
induced O
bradycardia O
was O
antagonized O
by O
prior O
bilateral O
vagotomy O
, O
but O
not O
spinal O
transection O
. O

Furthermore O
, O
selective O
destruction O
of O
the O
spinal O
5 B
- I
HT I
nerves O
, O
produced O
by O
bilateral O
spinal O
injection O
of O
5 B
, I
7 I
- I
dihydroxytryptamine I
, O
reduced O
the O
magnitude O
of O
the O
vasodepressor O
or O
the O
bradycardiac O
responses O
to O
clonidine B
microinjected O
into O
the O
area O
near O
the O
ventrolateral O
surface O
of O
the O
medulla O
oblongata O
in O
rats O
. O

The O
data O
indicate O
that O
a O
bulbospinal O
serotonergic O
pathway O
is O
involved O
in O
development O
of O
clonidine B
- O
induced O
hypotension O
and O
bradycardia O
. O

The O
induced O
hypotension O
is O
brought O
about O
by O
a O
decrease O
in O
sympathetic O
efferent O
activity O
, O
whereas O
the O
induced O
bradycardia O
was O
due O
to O
an O
increase O
in O
vagal O
efferent O
activity O
. O

Hypertension O
in O
neuroblastoma O
induced O
by O
imipramine B
. O

Hypertension O
is O
a O
well O
- O
known O
finding O
in O
some O
patients O
with O
neuroblastoma O
. O

However O
, O
it O
has O
not O
previously O
been O
described O
in O
association O
with O
the O
use O
of O
Imipramine B
. O

We O
report O
the O
occurrence O
of O
severe O
hypertension O
( O
blood O
pressure O
190 O
/ O
160 O
) O
in O
a O
4 O
- O
year O
- O
old O
girl O
with O
neuroblastoma O
who O
was O
given O
Imipramine B
to O
control O
a O
behavior O
disorder O
. O

It O
was O
determined O
later O
that O
this O
patient O
' O
s O
tumor O
was O
recurring O
at O
the O
time O
of O
her O
hypertensive O
episode O
. O

Since O
she O
had O
no O
blood O
pressure O
elevation O
at O
initial O
diagnosis O
and O
none O
following O
discontinuation O
of O
the O
Imipramine B
( O
when O
she O
was O
in O
florid O
relapse O
) O
, O
we O
believe O
that O
this O
drug O
rather O
than O
her O
underlying O
disease O
alone O
caused O
her O
hypertension O
. O

The O
mechanism O
for O
this O
reaction O
is O
believed O
to O
be O
increased O
levels O
of O
vasoactive O
catecholamines B
due O
to O
interference O
of O
their O
physiologic O
inactivation O
by O
Imipramine B
. O

From O
this O
experience O
, O
we O
urge O
extreme O
caution O
in O
the O
use O
of O
tricyclic O
antidepressants B
in O
children O
with O
active O
neuroblastoma O
. O

Rechallenge O
of O
patients O
who O
developed O
oral O
candidiasis O
or O
hoarseness O
with O
beclomethasone B
dipropionate I
. O

Of O
158 O
asthmatic O
patients O
who O
were O
placed O
on O
inhaled O
beclomethasone B
, O
15 O
( O
9 O
. O
5 O
% O
) O
developed O
either O
hoarseness O
( O
8 O
) O
, O
oral O
thrush O
( O
6 O
) O
, O
or O
both O
( O
1 O
) O
. O

When O
their O
adverse O
reactions O
subsided O
, O
seven O
of O
these O
15 O
patients O
were O
rechallenged O
with O
inhaled O
beclomethasone B
. O

These O
included O
five O
cases O
who O
developed O
hoarseness O
and O
three O
who O
developed O
Candidiasis O
. O

One O
patient O
had O
both O
. O

Oral O
thrush O
did O
not O
recur O
, O
but O
60 O
% O
( O
3 O
/ O
5 O
) O
of O
patients O
with O
hoarseness O
had O
recurrence O
. O

We O
conclude O
that O
patients O
may O
be O
restarted O
on O
inhaled O
beclomethasone B
when O
clinically O
indicated O
; O
however O
, O
because O
of O
the O
high O
recurrence O
rate O
, O
patients O
who O
develop O
hoarseness O
should O
not O
be O
re O
- O
challenged O
. O

Concomitant O
use O
of O
oral O
prednisone B
and O
topical O
beclomethasone B
may O
increase O
the O
risk O
of O
developing O
hoarseness O
or O
candidiasis O
. O

Cyclophosphamide B
cardiotoxicity O
: O
an O
analysis O
of O
dosing O
as O
a O
risk O
factor O
. O

Patients O
who O
undergo O
bone O
marrow O
transplantation O
are O
generally O
immunosuppressed O
with O
a O
dose O
of O
cyclophosphamide B
( O
CYA B
) O
which O
is O
usually O
calculated O
based O
on O
the O
patient O
' O
s O
weight O
. O

At O
these O
high O
doses O
of O
CYA B
, O
serious O
cardiotoxicity O
may O
occur O
, O
but O
definitive O
risk O
factors O
for O
the O
development O
of O
such O
cardiotoxicity O
have O
not O
been O
described O
. O

Since O
chemotherapeutic O
agent O
toxicity O
generally O
correlates O
with O
dose O
per O
body O
surface O
area O
, O
we O
retrospectively O
calculated O
the O
dose O
of O
CYA B
in O
patients O
transplanted O
at O
our O
institution O
to O
determine O
whether O
the O
incidence O
of O
CYA B
cardiotoxicity O
correlated O
with O
the O
dose O
per O
body O
surface O
area O
. O

Eighty O
patients O
who O
were O
to O
receive O
CYA B
50 O
mg O
/ O
kg O
/ O
d O
for O
four O
days O
as O
preparation O
for O
marrow O
grafting O
underwent O
a O
total O
of O
84 O
transplants O
for O
aplastic O
anemia O
, O
Wiskott O
- O
Aldrich O
syndrome O
, O
or O
severe O
combined O
immunodeficiency O
syndrome O
. O

Fourteen O
of O
84 O
( O
17 O
% O
) O
patients O
had O
symptoms O
and O
signs O
consistent O
with O
CYA B
cardiotoxicity O
within O
ten O
days O
of O
receiving O
1 O
to O
4 O
doses O
of O
CYA B
. O

Six O
of O
the O
14 O
patients O
died O
with O
congestive O
heart O
failure O
. O

The O
dose O
of O
CYA B
per O
body O
surface O
area O
was O
calculated O
for O
all O
patients O
and O
the O
patients O
were O
divided O
into O
two O
groups O
based O
on O
daily O
CYA B
dose O
: O
Group O
1 O
, O
CYA B
less O
than O
or O
equal O
to O
1 O
. O
55 O
g O
/ O
m2 O
/ O
d O
; O
Group O
2 O
, O
CYA B
greater O
than O
1 O
. O
55 O
g O
/ O
m2 O
/ O
d O
. O

Cardiotoxicity O
that O
was O
thought O
to O
be O
related O
to O
CYA B
occurred O
in O
1 O
/ O
32 O
( O
3 O
% O
) O
of O
patients O
in O
Group O
1 O
and O
in O
13 O
/ O
52 O
( O
25 O
% O
) O
patients O
in O
Group O
2 O
( O
P O
less O
than O
0 O
. O
025 O
) O
. O

Congestive O
heart O
failure O
caused O
or O
contributed O
to O
death O
in O
0 O
/ O
32 O
patients O
in O
Group O
1 O
v O
6 O
/ O
52 O
( O
12 O
% O
) O
of O
patients O
in O
Group O
2 O
( O
P O
less O
than O
0 O
. O
25 O
) O
. O

There O
was O
no O
difference O
in O
the O
rate O
of O
engraftment O
of O
evaluable O
patients O
in O
the O
two O
groups O
( O
P O
greater O
than O
0 O
. O
5 O
) O
. O

We O
conclude O
that O
the O
CYA B
cardiotoxicity O
correlates O
with O
CYA B
dosage O
as O
calculated O
by O
body O
surface O
area O
, O
and O
that O
patients O
with O
aplastic O
anemia O
and O
immunodeficiencies O
can O
be O
effectively O
prepared O
for O
bone O
marrow O
grafting O
at O
a O
CYA B
dose O
of O
1 O
. O
55 O
g O
/ O
m2 O
/ O
d O
for O
four O
days O
with O
a O
lower O
incidence O
of O
cardiotoxicity O
than O
patients O
whose O
CYA B
dosage O
is O
calculated O
based O
on O
weight O
. O

This O
study O
reaffirms O
the O
principle O
that O
drug O
toxicity O
correlates O
with O
dose O
per O
body O
surface O
area O
. O

Studies O
of O
risk O
factors O
for O
aminoglycoside B
nephrotoxicity O
. O

The O
epidemiology O
of O
aminoglycoside B
- O
induced O
nephrotoxicity O
is O
not O
fully O
understood O
. O

Experimental O
studies O
in O
healthy O
human O
volunteers O
indicate O
aminoglycosides B
cause O
proximal O
tubular O
damage O
in O
most O
patients O
, O
but O
rarely O
, O
if O
ever O
, O
cause O
glomerular O
or O
tubular O
dysfunction O
. O

Clinical O
trials O
of O
aminoglycosides B
in O
seriously O
ill O
patients O
indicate O
that O
the O
relative O
risk O
for O
developing O
acute O
renal O
failure O
during O
therapy O
ranges O
from O
8 O
to O
10 O
and O
that O
the O
attributable O
risk O
is O
70 O
% O
to O
80 O
% O
. O

Further O
analysis O
of O
these O
data O
suggests O
that O
the O
duration O
of O
therapy O
, O
plasma O
aminoglycoside B
levels O
, O
liver O
disease O
, O
advanced O
age O
, O
high O
initial O
estimated O
creatinine B
clearance O
and O
, O
possibly O
, O
female O
gender O
all O
increase O
the O
risk O
for O
nephrotoxicity O
. O

Other O
causes O
of O
acute O
renal O
failure O
, O
such O
as O
shock O
, O
appear O
to O
have O
an O
additive O
effect O
. O

Predictive O
models O
have O
been O
developed O
from O
these O
analyses O
that O
should O
be O
useful O
for O
identifying O
patients O
at O
high O
risk O
. O

These O
models O
may O
also O
be O
useful O
in O
developing O
insights O
into O
the O
pathophysiology O
of O
aminoglycoside B
- O
induced O
nephrotoxicity O
. O

Central O
action O
of O
narcotic O
analgesics O
. O

Part O
IV O
. O

Noradrenergic O
influences O
on O
the O
activity O
of O
analgesics O
in O
rats O
. O

The O
effect O
of O
clonidine B
, O
naphazoline B
and O
xylometazoline B
on O
analgesia O
induced O
by O
morphine B
, O
codeine B
, O
fentanyl B
and O
pentazocine B
, O
and O
on O
cataleptic O
effect O
of O
morphine B
, O
codine B
and O
fentanyl B
was O
studied O
in O
rats O
. O

The O
biochemical O
assays O
on O
the O
influence O
of O
four O
analgesics O
on O
the O
brain O
concentration O
and O
turnover O
of O
noradrenaline B
( O
NA B
) O
were O
also O
performed O
. O

It O
was O
found O
that O
three O
drugs O
stimulating O
central O
NA B
receptors O
failed O
to O
affect O
the O
analgesic O
ED50 O
of O
all O
antinociceptive O
agents O
and O
they O
enhanced O
catalepsy O
induced O
by O
morphine B
and O
fentanyl B
. O

Codeine B
catalepsy O
was O
increased O
by O
clonidine B
and O
decreased O
by O
naphazoline B
and O
xylometazoline B
. O

The O
brain O
concentration O
of O
NA B
was O
not O
changed O
by O
morphine B
and O
fentanyl B
, O
but O
one O
of O
the O
doses O
of O
codeine B
( O
45 O
mg O
/ O
kg O
) O
slightly O
enhanced O
it O
. O

Pentazocine B
dose O
- O
dependently O
decreased O
the O
brain O
level O
of O
NA B
. O

The O
rate O
of O
NA B
turnover O
was O
not O
altered O
by O
analgesics O
except O
for O
the O
higher O
dose O
of O
fentanyl B
( O
0 O
. O
2 O
mg O
/ O
kg O
) O
following O
which O
the O
disappearance O
of O
NA B
from O
the O
brain O
was O
diminished O
. O

The O
results O
are O
discussed O
in O
the O
light O
of O
various O
and O
non O
- O
uniform O
data O
from O
the O
literature O
. O

It O
is O
suggested O
that O
in O
rats O
the O
brain O
NA B
plays O
a O
less O
important O
function O
than O
the O
other O
monoamines O
in O
the O
behavioural O
activity O
of O
potent O
analgesics O
. O

Flurothyl B
seizure O
thresholds O
in O
mice O
treated O
neonatally O
with O
a O
single O
injection O
of O
monosodium B
glutamate I
( O
MSG B
) O
: O
evaluation O
of O
experimental O
parameters O
in O
flurothyl B
seizure O
testing O
. O

Monosodium B
glutamate I
( O
MSG B
) O
administration O
to O
neonatal O
rodents O
produces O
convulsions O
and O
results O
in O
numerous O
biochemical O
and O
behavioral O
deficits O
. O

These O
studies O
were O
undertaken O
to O
determine O
if O
neonatal O
administration O
of O
MSG B
produced O
permanent O
alterations O
in O
seizure O
susceptibility O
, O
since O
previous O
investigations O
were O
inconclusive O
. O

A O
flurothyl B
ether I
seizure O
screening O
technique O
was O
used O
to O
evaluate O
seizure O
susceptibility O
in O
adult O
mice O
that O
received O
neonatal O
injections O
of O
MSG B
( O
4 O
mg O
/ O
g O
and O
1 O
mg O
/ O
g O
) O
. O

MSG B
treatment O
resulted O
in O
significant O
reductions O
in O
whole O
brain O
weight O
but O
did O
not O
alter O
seizure O
threshold O
. O

A O
naloxone B
( O
5 O
mg O
/ O
kg O
) O
challenge O
was O
also O
ineffective O
in O
altering O
the O
seizure O
thresholds O
of O
either O
control O
of O
MSG B
- O
treated O
mice O
. O

Flurothyl B
ether I
produced O
hypothermia O
which O
was O
correlated O
with O
the O
duration O
of O
flurothyl B
exposure O
; O
however O
, O
the O
relationship O
of O
hypothermia O
to O
seizure O
induction O
was O
unclear O
. O

Flurothyl B
seizure O
testing O
proved O
to O
be O
a O
rapid O
and O
reliable O
technique O
with O
which O
to O
evaluate O
seizure O
susceptibility O
. O

Susceptibility O
to O
seizures O
produced O
by O
pilocarpine B
in O
rats O
after O
microinjection O
of O
isoniazid B
or O
gamma B
- I
vinyl I
- I
GABA I
into O
the O
substantia O
nigra O
. O

Pilocarpine B
, O
given O
intraperitoneally O
to O
rats O
, O
reproduces O
the O
neuropathological O
sequelae O
of O
temporal O
lobe O
epilepsy O
and O
provides O
a O
relevant O
animal O
model O
for O
studying O
mechanisms O
of O
buildup O
of O
convulsive O
activity O
and O
pathways O
operative O
in O
the O
generalization O
and O
propagation O
of O
seizures O
within O
the O
forebrain O
. O

In O
the O
present O
study O
, O
the O
effects O
of O
manipulating O
the O
activity O
of O
the O
gamma B
- I
aminobutyric I
acid I
( O
GABA B
) O
- O
mediated O
synaptic O
inhibition O
within O
the O
substantia O
nigra O
on O
seizures O
produced O
by O
pilocarpine B
in O
rats O
, O
were O
investigated O
. O

In O
animals O
pretreated O
with O
microinjections O
of O
isoniazid B
, O
150 O
micrograms O
, O
an O
inhibitor O
of O
activity O
of O
the O
GABA B
- O
synthesizing O
enzyme O
, O
L B
- I
glutamic B
acid I
decarboxylase O
, O
into O
the O
substantia O
nigra O
pars O
reticulata O
( O
SNR O
) O
, O
bilaterally O
, O
non O
- O
convulsant O
doses O
of O
pilocarpine B
, O
100 O
and O
200 O
mg O
/ O
kg O
, O
resulted O
in O
severe O
motor O
limbic O
seizures O
and O
status O
epilepticus O
. O

Electroencephalographic O
and O
behavioral O
monitoring O
revealed O
a O
profound O
reduction O
of O
the O
threshold O
for O
pilocarpine B
- O
induced O
convulsions O
. O

Morphological O
analysis O
of O
frontal O
forebrain O
sections O
with O
light O
microscopy O
revealed O
seizure O
- O
related O
damage O
to O
the O
hippocampal O
formation O
, O
thalamus O
, O
amygdala O
, O
olfactory O
cortex O
, O
substantia O
nigra O
and O
neocortex O
, O
which O
is O
typically O
observed O
with O
pilocarpine B
in O
doses O
exceeding O
350 O
mg O
/ O
kg O
. O

Bilateral O
intrastriatal O
injections O
of O
isoniazid B
did O
not O
augment O
seizures O
produced O
by O
pilocarpine B
, O
200 O
mg O
/ O
kg O
. O

Application O
of O
an O
irreversible O
inhibitor O
of O
GABA B
transaminase O
, O
gamma B
- I
vinyl I
- I
GABA I
( O
D B
, I
L I
- I
4 I
- I
amino I
- I
hex I
- I
5 I
- I
enoic I
acid I
) O
, O
5 O
micrograms O
, O
into O
the O
SNR O
, O
bilaterally O
, O
suppressed O
the O
appearance O
of O
electrographic O
and O
behavioral O
seizures O
produced O
by O
pilocarpine B
, O
380 O
mg O
/ O
kg O
. O

This O
treatment O
was O
also O
sufficient O
to O
protect O
animals O
from O
the O
occurrence O
of O
brain O
damage O
. O

Microinjections O
of O
gamma B
- I
vinyl I
- I
GABA I
, O
5 O
micrograms O
, O
into O
the O
dorsal O
striatum O
, O
bilaterally O
, O
failed O
to O
prevent O
the O
development O
of O
convulsions O
produced O
by O
pilocarpine B
, O
380 O
mg O
/ O
kg O
. O

The O
results O
demonstrate O
that O
the O
threshold O
for O
pilocarpine B
- O
induced O
seizures O
in O
rats O
is O
subjected O
to O
the O
regulation O
of O
the O
GABA B
- O
mediated O
synaptic O
inhibition O
within O
the O
substantia O
nigra O
. O

Human O
and O
canine O
ventricular O
vasoactive O
intestinal O
polypeptide O
: O
decrease O
with O
heart O
failure O
. O

Vasoactive O
intestinal O
polypeptide O
( O
VIP O
) O
is O
a O
systemic O
and O
coronary O
vasodilator O
that O
may O
have O
positive O
inotropic O
properties O
. O

Myocardial O
levels O
of O
VIP O
were O
assayed O
before O
and O
after O
the O
development O
of O
heart O
failure O
in O
two O
canine O
models O
. O

In O
the O
first O
, O
cobalt B
cardiomyopathy O
was O
induced O
in O
eight O
dogs O
; O
VIP O
( O
by O
radioimmunoassay O
) O
decreased O
from O
35 O
+ O
/ O
- O
11 O
pg O
/ O
mg O
protein O
( O
mean O
+ O
/ O
- O
SD O
) O
to O
5 O
+ O
/ O
- O
4 O
pg O
/ O
mg O
protein O
( O
P O
less O
than O
0 O
. O
05 O
) O
. O

In O
six O
dogs O
with O
doxorubicin B
- O
induced O
heart O
failure O
, O
VIP O
decreased O
from O
31 O
+ O
/ O
- O
7 O
to O
11 O
+ O
/ O
- O
4 O
pg O
/ O
mg O
protein O
( O
P O
less O
than O
0 O
. O
05 O
) O
. O

In O
addition O
, O
VIP O
content O
of O
left O
ventricular O
muscle O
of O
resected O
failing O
hearts O
in O
10 O
patients O
receiving O
a O
heart O
transplant O
was O
compared O
with O
the O
papillary O
muscles O
in O
14 O
patients O
( O
five O
with O
rheumatic O
disease O
, O
nine O
with O
myxomatous O
degeneration O
) O
receiving O
mitral O
valve O
prostheses O
. O

The O
lowest O
myocardial O
VIP O
concentration O
was O
found O
in O
the O
hearts O
of O
patients O
with O
coronary O
disease O
( O
one O
patient O
receiving O
a O
transplant O
and O
three O
receiving O
mitral O
prostheses O
) O
( O
6 O
. O
3 O
+ O
/ O
- O
1 O
. O
9 O
pg O
/ O
mg O
protein O
) O
. O

The O
other O
patients O
undergoing O
transplantation O
had O
an O
average O
ejection O
fraction O
of O
17 O
% O
+ O
/ O
- O
6 O
% O
and O
a O
VIP O
level O
of O
8 O
. O
8 O
+ O
/ O
- O
3 O
. O
9 O
pg O
/ O
mg O
protein O
. O

The O
hearts O
without O
coronary O
artery O
disease O
( O
average O
ejection O
fraction O
of O
this O
group O
62 O
% O
+ O
/ O
- O
10 O
% O
) O
had O
a O
VIP O
concentration O
of O
14 O
. O
1 O
+ O
/ O
- O
7 O
. O
9 O
pg O
/ O
mg O
protein O
, O
and O
this O
was O
greater O
than O
in O
hearts O
of O
the O
patients O
with O
coronary O
disease O
and O
the O
hearts O
of O
patients O
receiving O
a O
transplant O
( O
P O
less O
than O
0 O
. O
05 O
) O
. O

Myocardial O
catecholamines B
were O
also O
determined O
in O
14 O
subjects O
; O
a O
weak O
correlation O
( O
r O
= O
0 O
. O
57 O
, O
P O
less O
than O
0 O
. O
05 O
) O
between O
the O
tissue O
concentrations O
of O
VIP O
and O
norepinephrine B
was O
noted O
. O
( O
ABSTRACT O
TRUNCATED O
AT O
250 O
WORDS O
) O

Non O
- O
invasive O
detection O
of O
coronary O
artery O
disease O
by O
body O
surface O
electrocardiographic O
mapping O
after O
dipyridamole B
infusion O
. O

Electrocardiographic O
changes O
after O
dipyridamole B
infusion O
( O
0 O
. O
568 O
mg O
/ O
kg O
/ O
4 O
min O
) O
were O
studied O
in O
41 O
patients O
with O
coronary O
artery O
disease O
and O
compared O
with O
those O
after O
submaximal O
treadmill O
exercise O
by O
use O
of O
the O
body O
surface O
mapping O
technique O
. O

Patients O
were O
divided O
into O
three O
groups O
; O
19 O
patients O
without O
myocardial O
infarction O
( O
non O
- O
MI O
group O
) O
, O
14 O
with O
anterior O
infarction O
( O
ANT O
- O
MI O
) O
and O
eight O
with O
inferior O
infarction O
( O
INF O
- O
MI O
) O
. O

Eighty O
- O
seven O
unipolar O
electrocardiograms O
( O
ECGs O
) O
distributed O
over O
the O
entire O
thoracic O
surface O
were O
simultaneously O
recorded O
. O

After O
dipyridamole B
, O
ischemic O
ST O
- O
segment O
depression O
( O
0 O
. O
05 O
mV O
or O
more O
) O
was O
observed O
in O
84 O
% O
of O
the O
non O
- O
MI O
group O
, O
29 O
% O
of O
the O
ANT O
- O
MI O
group O
, O
63 O
% O
of O
the O
INF O
- O
MI O
group O
and O
61 O
% O
of O
the O
total O
population O
. O

Exercise O
- O
induced O
ST O
depression O
was O
observed O
in O
84 O
% O
of O
the O
non O
- O
MI O
group O
, O
43 O
% O
of O
the O
ANT O
- O
MI O
group O
, O
38 O
% O
of O
the O
INF O
- O
MI O
group O
and O
61 O
% O
of O
the O
total O
. O

For O
individual O
patients O
, O
there O
were O
no O
obvious O
differences O
between O
the O
body O
surface O
distribution O
of O
ST O
depression O
in O
both O
tests O
. O

The O
increase O
in O
pressure O
rate O
product O
after O
dipyridamole B
was O
significantly O
less O
than O
that O
during O
the O
treadmill O
exercise O
. O

The O
data O
suggest O
that O
the O
dipyridamole B
- O
induced O
myocardial O
ischemia O
is O
caused O
by O
the O
inhomogenous O
distribution O
of O
myocardial O
blood O
flow O
. O

We O
conclude O
that O
the O
dipyridamole B
ECG O
test O
is O
as O
useful O
as O
the O
exercise O
ECG O
test O
for O
the O
assessment O
of O
coronary O
artery O
disease O
. O

Bradycardia O
after O
high O
- O
dose O
intravenous O
methylprednisolone B
therapy O
. O

In O
5 O
consecutive O
patients O
with O
rheumatoid O
arthritis O
who O
received O
intravenous O
high O
- O
dose O
methylprednisolone B
( O
MP B
) O
therapy O
( O
1 O
g O
daily O
for O
2 O
or O
3 O
consecutive O
days O
) O
, O
a O
decline O
in O
pulse O
rate O
was O
observed O
, O
most O
pronounced O
on O
day O
4 O
. O

In O
one O
of O
the O
5 O
patients O
the O
bradycardia O
was O
associated O
with O
complaints O
of O
substernal O
pressure O
. O

Reversal O
to O
normal O
heart O
rate O
was O
found O
on O
day O
7 O
. O

Electrocardiographic O
registrations O
showed O
sinus O
bradycardia O
in O
all O
cases O
. O

No O
significant O
changes O
in O
plasma O
concentrations O
of O
electrolytes O
were O
found O
. O

Careful O
observation O
of O
patients O
receiving O
high O
- O
dose O
MP B
is O
recommended O
. O

High O
- O
dose O
MP B
may O
be O
contraindicated O
in O
patients O
with O
known O
heart O
disease O
. O

Two O
cases O
of O
downbeat O
nystagmus O
and O
oscillopsia O
associated O
with O
carbamazepine B
. O

Downbeat O
nystagmus O
is O
often O
associated O
with O
structural O
lesions O
at O
the O
craniocervical O
junction O
, O
but O
has O
occasionally O
been O
reported O
as O
a O
manifestation O
of O
metabolic O
imbalance O
or O
drug O
intoxication O
. O

We O
recorded O
the O
eye O
movements O
of O
two O
patients O
with O
reversible O
downbeat O
nystagmus O
related O
to O
carbamazepine B
therapy O
. O

The O
nystagmus O
of O
both O
patients O
resolved O
after O
reduction O
of O
the O
serum O
carbamazepine B
levels O
. O

Neuroradiologic O
investigations O
including O
magnetic O
resonance O
imaging O
scans O
in O
both O
patients O
showed O
no O
evidence O
of O
intracranial O
abnormality O
. O

In O
patients O
with O
downbeat O
nystagmus O
who O
are O
taking O
anticonvulsant O
medications O
, O
consideration O
should O
be O
given O
to O
reduction O
in O
dose O
before O
further O
investigation O
is O
undertaken O
. O

Improvement O
by O
denopamine B
( O
TA B
- I
064 I
) O
of O
pentobarbital B
- O
induced O
cardiac O
failure O
in O
the O
dog O
heart O
- O
lung O
preparation O
. O

The O
efficacy O
of O
denopamine B
, O
an O
orally O
active O
beta O
1 O
- O
adrenoceptor O
agonist O
, O
in O
improving O
cardiac O
failure O
was O
assessed O
in O
dog O
heart O
- O
lung O
preparations O
. O

Cardiac O
functions O
depressed O
by O
pentobarbital B
( O
118 O
+ O
/ O
- O
28 O
mg O
; O
mean O
value O
+ O
/ O
- O
SD O
) O
such O
that O
cardiac O
output O
and O
maximum O
rate O
of O
rise O
of O
left O
ventricular O
pressure O
( O
LV O
dP O
/ O
dt O
max O
) O
had O
been O
reduced O
by O
about O
35 O
% O
and O
26 O
% O
of O
the O
respective O
controls O
were O
improved O
by O
denopamine B
( O
10 O
- O
300 O
micrograms O
) O
in O
a O
dose O
- O
dependent O
manner O
. O

With O
100 O
micrograms O
denopamine B
, O
almost O
complete O
restoration O
of O
cardiac O
performance O
was O
attained O
, O
associated O
with O
a O
slight O
increase O
in O
heart O
rate O
. O

No O
arrhythmias O
were O
induced O
by O
these O
doses O
of O
denopamine B
. O

The O
results O
warrant O
clinical O
trials O
of O
denopamine B
in O
the O
treatment O
of O
cardiac O
failure O
. O

Clonazepam B
monotherapy O
for O
epilepsy O
in O
childhood O
. O

Sixty O
patients O
( O
age O
- O
range O
one O
month O
to O
14 O
years O
) O
with O
other O
types O
of O
epilepsy O
than O
infantile O
spasms O
were O
treated O
with O
clonazepam B
. O

Disappearance O
of O
seizures O
and O
normalization O
of O
abnormal O
EEG O
with O
disappearance O
of O
seizures O
were O
recognized O
in O
77 O
% O
and O
50 O
% O
, O
respectively O
. O

Seizures O
disappeared O
in O
71 O
% O
of O
the O
patients O
with O
generalized O
seizures O
and O
89 O
% O
of O
partial O
seizures O
. O

Improvement O
of O
abnormal O
EEG O
was O
noticed O
in O
76 O
% O
of O
diffuse O
paroxysms O
and O
in O
67 O
% O
of O
focal O
paroxysms O
. O

In O
excellent O
cases O
, O
mean O
effective O
dosages O
were O
0 O
. O
086 O
+ O
/ O
- O
0 O
. O
021 O
mg O
/ O
kg O
/ O
day O
in O
infants O
and O
0 O
. O
057 O
+ O
/ O
- O
0 O
. O
022 O
mg O
/ O
kg O
/ O
day O
in O
schoolchildren O
, O
this O
difference O
was O
statistically O
significant O
( O
p O
less O
than O
0 O
. O
005 O
) O
. O

The O
incidence O
of O
side O
effects O
such O
as O
drowsiness O
and O
ataxia O
was O
only O
5 O
% O
. O

Postmarketing O
study O
of O
timolol B
- O
hydrochlorothiazide B
antihypertensive O
therapy O
. O

A O
postmarketing O
surveillance O
study O
was O
conducted O
to O
determine O
the O
safety O
and O
efficacy O
of O
a O
fixed O
- O
ratio O
combination O
containing O
10 O
mg O
of O
timolol B
maleate I
and O
25 O
mg O
of O
hydrochlorothiazide B
, O
administered O
twice O
daily O
for O
one O
month O
to O
hypertensive O
patients O
. O

Data O
on O
9 O
, O
037 O
patients O
were O
collected O
by O
1 O
, O
455 O
participating O
physicians O
. O

Mean O
systolic O
blood O
pressure O
decreased O
25 O
mmHg O
and O
mean O
diastolic O
blood O
pressure O
declined O
15 O
mmHg O
after O
one O
month O
of O
timolol B
- O
hydrochlorothiazide B
therapy O
( O
P O
less O
than O
0 O
. O
01 O
, O
both O
comparisons O
) O
. O

Age O
, O
race O
, O
and O
sex O
appeared O
to O
have O
no O
influence O
on O
the O
decrease O
in O
blood O
pressure O
. O

The O
antihypertensive O
effect O
of O
the O
drug O
was O
greater O
in O
patients O
with O
more O
severe O
hypertension O
. O

Overall O
, O
1 O
, O
453 O
patients O
experienced O
a O
total O
of O
2 O
, O
658 O
adverse O
events O
, O
the O
most O
common O
being O
fatigue O
, O
dizziness O
, O
and O
weakness O
. O

Treatment O
in O
590 O
patients O
was O
discontinued O
because O
of O
adverse O
events O
. O

Salicylate B
nephropathy O
in O
the O
Gunn O
rat O
: O
potential O
role O
of O
prostaglandins B
. O

We O
examined O
the O
potential O
role O
of O
prostaglandins B
in O
the O
development O
of O
analgesic O
nephropathy O
in O
the O
Gunn O
strain O
of O
rat O
. O

The O
homozygous O
Gunn O
rats O
have O
unconjugated O
hyperbilirubinemia O
due O
to O
the O
absence O
of O
glucuronyl O
transferase O
, O
leading O
to O
marked O
bilirubin B
deposition O
in O
renal O
medulla O
and O
papilla O
. O

These O
rats O
are O
also O
highly O
susceptible O
to O
develop O
papillary O
necrosis O
with O
analgesic O
administration O
. O

We O
used O
homozygous O
( O
jj O
) O
and O
phenotypically O
normal O
heterozygous O
( O
jJ O
) O
animals O
. O

Four O
groups O
of O
rats O
( O
n O
= O
7 O
) O
were O
studied O
: O
jj O
and O
jJ O
rats O
treated O
either O
with O
aspirin B
300 O
mg O
/ O
kg O
every O
other O
day O
or O
sham O
- O
treated O
. O

After O
one O
week O
, O
slices O
of O
cortex O
, O
outer O
and O
inner O
medulla O
from O
one O
kidney O
were O
incubated O
in O
buffer O
and O
prostaglandin B
synthesis O
was O
determined O
by O
radioimmunoassay O
. O

The O
other O
kidney O
was O
examined O
histologically O
. O

A O
marked O
corticomedullary O
gradient O
of O
prostaglandin B
synthesis O
was O
observed O
in O
all O
groups O
. O

PGE2 B
synthesis O
was O
significantly O
higher O
in O
outer O
medulla O
, O
but O
not O
cortex O
or O
inner O
medulla O
, O
of O
jj O
( O
38 O
+ O
/ O
- O
6 O
ng O
/ O
mg O
prot O
) O
than O
jJ O
rats O
( O
15 O
+ O
/ O
- O
3 O
) O
( O
p O
less O
than O
0 O
. O
01 O
) O
. O

Aspirin B
treatment O
reduced O
PGE2 B
synthesis O
in O
all O
regions O
, O
but O
outer O
medullary O
PGE2 B
remained O
higher O
in O
jj O
( O
18 O
+ O
/ O
- O
3 O
) O
than O
jJ O
rats O
( O
9 O
+ O
/ O
- O
2 O
) O
( O
p O
less O
than O
0 O
. O
05 O
) O
. O

PGF2 B
alpha I
was O
also O
significantly O
higher O
in O
the O
outer O
medulla O
of O
jj O
rats O
with O
and O
without O
aspirin B
administration O
( O
p O
less O
than O
0 O
. O
05 O
) O
. O

The O
changes O
in O
renal O
prostaglandin B
synthesis O
were O
accompanied O
by O
evidence O
of O
renal O
damage O
in O
aspirin B
- O
treated O
jj O
but O
not O
jJ O
rats O
as O
evidenced O
by O
: O
increased O
incidence O
and O
severity O
of O
hematuria O
( O
p O
less O
than O
0 O
. O
01 O
) O
; O
increased O
serum O
creatinine B
( O
p O
less O
than O
0 O
. O
05 O
) O
; O
and O
increase O
in O
outer O
medullary O
histopathologic O
lesions O
( O
p O
less O
than O
0 O
. O
005 O
compared O
to O
either O
sham O
- O
treated O
jj O
or O
aspirin B
- O
treated O
jJ O
) O
. O

These O
results O
suggest O
that O
enhanced O
prostaglandin B
synthesis O
contributes O
to O
maintenance O
of O
renal O
function O
and O
morphological O
integrity O
, O
and O
that O
inhibition O
of O
prostaglandin B
synthesis O
may O
lead O
to O
pathological O
renal O
medullary O
lesions O
and O
deterioration O
of O
renal O
function O
. O

Prophylactic O
lidocaine B
in O
the O
early O
phase O
of O
suspected O
myocardial O
infarction O
. O

Four O
hundred O
two O
patients O
with O
suspected O
myocardial O
infarction O
seen O
within O
6 O
hours O
of O
the O
onset O
of O
symptoms O
entered O
a O
double O
- O
blind O
randomized O
trial O
of O
lidocaine B
vs O
placebo O
. O

During O
the O
1 O
hour O
after O
administration O
of O
the O
drug O
the O
incidence O
of O
ventricular O
fibrillation O
or O
sustained O
ventricular O
tachycardia O
among O
the O
204 O
patients O
with O
acute O
myocardial O
infarction O
was O
low O
, O
1 O
. O
5 O
% O
. O

Lidocaine B
, O
given O
in O
a O
300 O
mg O
dose O
intramuscularly O
followed O
by O
100 O
mg O
intravenously O
, O
did O
not O
prevent O
sustained O
ventricular O
tachycardia O
, O
although O
there O
was O
a O
significant O
reduction O
in O
the O
number O
of O
patients O
with O
warning O
arrhythmias O
between O
15 O
and O
45 O
minutes O
after O
the O
administration O
of O
lidocaine B
( O
p O
less O
than O
0 O
. O
05 O
) O
. O

The O
average O
plasma O
lidocaine B
level O
10 O
minutes O
after O
administration O
for O
patients O
without O
a O
myocardial O
infarction O
was O
significantly O
higher O
than O
that O
for O
patients O
with O
an O
acute O
infarction O
. O

The O
mean O
plasma O
lidocaine B
level O
of O
patients O
on O
beta O
- O
blocking O
agents O
was O
no O
different O
from O
that O
in O
patients O
not O
on O
beta O
blocking O
agents O
. O

During O
the O
1 O
- O
hour O
study O
period O
, O
the O
incidence O
of O
central O
nervous O
system O
side O
effects O
was O
significantly O
greater O
in O
the O
lidocaine B
group O
, O
hypotension O
occurred O
in O
11 O
patients O
, O
nine O
of O
whom O
had O
received O
lidocaine B
, O
and O
four O
patients O
died O
from O
asystole O
, O
three O
of O
whom O
had O
had O
lidocaine B
. O

We O
cannot O
advocate O
the O
administration O
of O
lidocaine B
prophylactically O
in O
the O
early O
hours O
of O
suspected O
myocardial O
infarction O
. O

Evidence O
for O
a O
cholinergic O
role O
in O
haloperidol B
- O
induced O
catalepsy O
. O

Experiments O
in O
mice O
tested O
previous O
evidence O
that O
activation O
of O
cholinergic O
systems O
promotes O
catalepsy O
and O
that O
cholinergic O
mechanisms O
need O
to O
be O
intact O
for O
full O
expression O
of O
neuroleptic O
- O
induced O
catalepsy O
. O

Large O
doses O
of O
the O
cholinomimetic O
, O
pilocarpine B
, O
could O
induce O
catalepsy O
when O
peripheral O
cholinergic O
receptors O
were O
blocked O
. O

Low O
doses O
of O
pilocarpine B
caused O
a O
pronounced O
enhancement O
of O
the O
catalepsy O
that O
was O
induced O
by O
the O
dopaminergic O
blocker O
, O
haloperidol B
. O

A O
muscarinic O
receptor O
blocker O
, O
atropine B
, O
disrupted O
haloperidol B
- O
induced O
catalepsy O
. O

Intracranial O
injection O
of O
an O
acetylcholine B
- O
synthesis O
inhibitor O
, O
hemicholinium B
, O
prevented O
the O
catalepsy O
that O
is O
usually O
induced O
by O
haloperidol B
. O

These O
findings O
suggest O
the O
hypothesis O
that O
the O
catalepsy O
that O
is O
produced O
by O
neuroleptics O
such O
as O
haloperidol B
is O
actually O
mediated O
by O
intrinsic O
central O
cholinergic O
systems O
. O

Alternatively O
, O
activation O
of O
central O
cholinergic O
systems O
could O
promote O
catalepsy O
by O
suppression O
of O
dopaminergic O
systems O
. O

Cardiovascular O
dysfunction O
and O
hypersensitivity O
to O
sodium B
pentobarbital I
induced O
by O
chronic O
barium B
chloride I
ingestion O
. O

Barium B
- O
supplemented O
Long O
- O
Evans O
hooded O
rats O
were O
characterized O
by O
a O
persistent O
hypertension O
that O
was O
evident O
after O
1 O
month O
of O
barium B
( O
100 O
micrograms O
/ O
ml O
mineral O
fortified O
water O
) O
treatment O
. O

Analysis O
of O
in O
vivo O
myocardial O
excitability O
, O
contractility O
, O
and O
metabolic O
characteristics O
at O
16 O
months O
revealed O
other O
significant O
barium B
- O
induced O
disturbances O
within O
the O
cardiovascular O
system O
. O

The O
most O
distinctive O
aspect O
of O
the O
barium B
effect O
was O
a O
demonstrated O
hypersensitivity O
of O
the O
cardiovascular O
system O
to O
sodium B
pentobarbital I
. O

Under O
barbiturate B
anesthesia O
, O
virtually O
all O
of O
the O
myocardial O
contractile O
indices O
were O
depressed O
significantly O
in O
barium B
- O
exposed O
rats O
relative O
to O
the O
corresponding O
control O
- O
fed O
rats O
. O

The O
lack O
of O
a O
similar O
response O
to O
ketamine B
and O
xylazine B
anesthesia O
revealed O
that O
the O
cardiovascular O
actions O
of O
sodium B
pentobarbital I
in O
barium B
- O
treated O
rats O
were O
linked O
specifically O
to O
this O
anesthetic O
, O
and O
were O
not O
representative O
of O
a O
generalized O
anesthetic O
response O
. O

Other O
myocardial O
pathophysiologic O
and O
metabolic O
changes O
induced O
by O
barium B
were O
manifest O
, O
irrespective O
of O
the O
anesthetic O
employed O
. O

The O
contractile O
element O
shortening O
velocity O
of O
the O
cardiac O
muscle O
fibers O
was O
significantly O
slower O
in O
both O
groups O
of O
barium B
- O
treated O
rats O
relative O
to O
the O
control O
groups O
, O
irrespective O
of O
the O
anesthetic O
regimen O
. O

Similarly O
, O
significant O
disturbances O
in O
myocardial O
energy O
metabolism O
were O
detected O
in O
the O
barium B
- O
exposed O
rats O
which O
were O
consistent O
with O
the O
reduced O
contractile O
element O
shortening O
velocity O
. O

In O
addition O
, O
the O
excitability O
of O
the O
cardiac O
conduction O
system O
was O
depressed O
preferentially O
in O
the O
atrioventricular O
nodal O
region O
of O
hearts O
from O
barium B
- O
exposed O
rats O
. O

Overall O
, O
the O
altered O
cardiac O
contractility O
and O
excitability O
characteristics O
, O
the O
myocardial O
metabolic O
disturbances O
, O
and O
the O
hypersensitivity O
of O
the O
cardiovascular O
system O
to O
sodium B
pentobarbital I
suggest O
the O
existence O
of O
a O
heretofore O
undescribed O
cardiomyopathic O
disorder O
induced O
by O
chronic O
barium B
exposure O
. O

These O
experimental O
findings O
represent O
the O
first O
indication O
that O
life O
- O
long O
barium B
ingestion O
may O
have O
significant O
adverse O
effects O
on O
the O
mammalian O
cardiovascular O
system O
. O

Propranolol B
antagonism O
of O
phenylpropanolamine B
- O
induced O
hypertension O
. O

Phenylpropanolamine B
( O
PPA B
) O
overdose O
can O
cause O
severe O
hypertension O
, O
intracerebral O
hemorrhage O
, O
and O
death O
. O

We O
studied O
the O
efficacy O
and O
safety O
of O
propranolol B
in O
the O
treatment O
of O
PPA B
- O
induced O
hypertension O
. O

Subjects O
received O
propranolol B
either O
by O
mouth O
for O
48 O
hours O
before O
PPA B
or O
as O
a O
rapid O
intravenous O
infusion O
after O
PPA B
. O

PPA B
, O
75 O
mg O
alone O
, O
increased O
blood O
pressure O
( O
31 O
+ O
/ O
- O
14 O
mm O
Hg O
systolic O
, O
20 O
+ O
/ O
- O
5 O
mm O
Hg O
diastolic O
) O
, O
and O
propranolol B
pretreatment O
antagonized O
this O
increase O
( O
12 O
+ O
/ O
- O
10 O
mm O
Hg O
systolic O
, O
10 O
+ O
/ O
- O
7 O
mm O
Hg O
diastolic O
) O
. O

Intravenous O
propranolol B
after O
PPA B
also O
decreased O
blood O
pressure O
. O

Left O
ventricular O
function O
( O
assessed O
by O
echocardiography O
) O
showed O
that O
PPA B
increased O
the O
stroke O
volume O
30 O
% O
( O
from O
62 O
. O
5 O
+ O
/ O
- O
20 O
. O
9 O
to O
80 O
. O
8 O
+ O
/ O
- O
22 O
. O
4 O
ml O
) O
, O
the O
ejection O
fraction O
9 O
% O
( O
from O
64 O
% O
+ O
/ O
- O
10 O
% O
to O
70 O
% O
+ O
/ O
- O
7 O
% O
) O
, O
and O
cardiac O
output O
14 O
% O
( O
from O
3 O
. O
6 O
+ O
/ O
- O
0 O
. O
6 O
to O
4 O
. O
1 O
+ O
/ O
- O
1 O
. O
0 O
L O
/ O
min O
) O
. O

Intravenous O
propranolol B
reversed O
these O
effects O
. O

Systemic O
vascular O
resistance O
was O
increased O
by O
PPA B
28 O
% O
( O
from O
1710 O
+ O
/ O
- O
200 O
to O
2190 O
+ O
/ O
- O
700 O
dyne O
X O
sec O
/ O
cm5 O
) O
and O
was O
further O
increased O
by O
propranolol B
22 O
% O
( O
to O
2660 O
+ O
/ O
- O
1200 O
dyne O
X O
sec O
/ O
cm5 O
) O
. O

We O
conclude O
that O
PPA B
increases O
blood O
pressure O
by O
increasing O
systemic O
vascular O
resistance O
and O
cardiac O
output O
, O
and O
that O
propranolol B
antagonizes O
this O
increase O
by O
reversing O
the O
effect O
of O
PPA B
on O
cardiac O
output O
. O

That O
propranolol B
antagonizes O
the O
pressor O
effect O
of O
PPA B
is O
in O
contrast O
to O
the O
interaction O
in O
which O
propranolol B
enhances O
the O
pressor O
effect O
of O
norepinephrine B
. O

This O
is O
probably O
because O
PPA B
has O
less O
beta O
2 O
activity O
than O
does O
norepinephrine B
. O

Mesangial O
function O
and O
glomerular O
sclerosis O
in O
rats O
with O
aminonucleoside B
nephrosis O
. O

The O
possible O
relationship O
between O
mesangial O
dysfunction O
and O
development O
of O
glomerular O
sclerosis O
was O
studied O
in O
the O
puromycin B
aminonucleoside I
( O
PAN B
) O
model O
. O

Five O
male O
Wistar O
rats O
received O
repeated O
subcutaneous O
PAN B
injections O
; O
five O
controls O
received O
saline O
only O
. O

After O
4 O
weeks O
the O
PAN B
rats O
were O
severely O
proteinuric O
( O
190 O
+ O
/ O
- O
80 O
mg O
/ O
24 O
hr O
) O
, O
and O
all O
rats O
were O
given O
colloidal O
carbon B
( O
CC B
) O
intravenously O
. O

At O
5 O
months O
glomerular O
sclerosis O
was O
found O
in O
7 O
. O
6 O
+ O
/ O
- O
3 O
. O
4 O
% O
of O
the O
glomeruli O
of O
PAN O
rats O
; O
glomeruli O
of O
the O
controls O
were O
normal O
. O

Glomeruli O
of O
PAN O
rats O
contained O
significantly O
more O
CC B
than O
glomeruli O
of O
controls O
. O

Glomeruli O
with O
sclerosis O
contained O
significantly O
more O
CC B
than O
non O
- O
sclerotic O
glomeruli O
in O
the O
same O
kidneys O
. O

CC B
was O
preferentially O
localized O
within O
the O
sclerotic O
areas O
of O
the O
affected O
glomeruli O
. O

Since O
mesangial O
CC B
clearance O
from O
the O
mesangium O
did O
not O
change O
during O
chronic O
PAN B
treatment O
, O
we O
conclude O
that O
this O
preferential O
CC B
localization O
within O
the O
lesions O
is O
caused O
by O
an O
increased O
CC B
uptake O
shortly O
after O
injection O
in O
apparent O
vulnerable O
areas O
where O
sclerosis O
will O
develop O
subsequently O
. O

Cluster O
analysis O
showed O
a O
random O
distribution O
of O
lesions O
in O
the O
PAN O
glomeruli O
in O
concordance O
with O
the O
random O
localization O
of O
mesangial O
areas O
with O
dysfunction O
in O
this O
model O
. O

Similar O
to O
the O
remnant O
kidney O
model O
in O
PAN B
nephrosis O
the O
development O
of O
glomerular O
sclerosis O
may O
be O
related O
to O
" O
mesangial O
overloading O
. O
" O

Relationship O
between O
nicotine B
- O
induced O
seizures O
and O
hippocampal O
nicotinic O
receptors O
. O

A O
controversy O
has O
existed O
for O
several O
years O
concerning O
the O
physiological O
relevance O
of O
the O
nicotinic O
receptor O
measured O
by O
alpha B
- I
bungarotoxin I
binding O
. O

Using O
mice O
derived O
from O
a O
classical O
F2 O
and O
backcross O
genetic O
design O
, O
a O
relationship O
between O
nicotine B
- O
induced O
seizures O
and O
alpha B
- I
bungarotoxin I
nicotinic O
receptor O
concentration O
was O
found O
. O

Mice O
sensitive O
to O
the O
convulsant O
effects O
of O
nicotine B
had O
greater O
alpha B
- I
bungarotoxin I
binding O
in O
the O
hippocampus O
than O
seizure O
insensitive O
mice O
. O

The O
binding O
sites O
from O
seizure O
sensitive O
and O
resistant O
mice O
were O
equally O
affected O
by O
treatment O
with O
dithiothreitol B
, O
trypsin O
or O
heat O
. O

Thus O
it O
appears O
that O
the O
difference O
between O
seizure O
sensitive O
and O
insensitive O
animals O
may O
be O
due O
to O
a O
difference O
in O
hippocampal O
nicotinic O
receptor O
concentration O
as O
measured O
with O
alpha B
- I
bungarotoxin I
binding O
. O

The O
role O
of O
p B
- I
aminophenol I
in O
acetaminophen B
- O
induced O
nephrotoxicity O
: O
effect O
of O
bis B
( I
p I
- I
nitrophenyl I
) I
phosphate I
on O
acetaminophen B
and O
p B
- I
aminophenol I
nephrotoxicity O
and O
metabolism O
in O
Fischer O
344 O
rats O
. O

Acetaminophen B
( O
APAP B
) O
produces O
proximal O
tubular O
necrosis O
in O
Fischer O
344 O
( O
F344 O
) O
rats O
. O

Recently O
, O
p B
- I
aminophenol I
( O
PAP B
) O
, O
a O
known O
potent O
nephrotoxicant O
, O
was O
identified O
as O
a O
metabolite O
of O
APAP B
in O
F344 O
rats O
. O

The O
purpose O
of O
this O
study O
was O
to O
determine O
if O
PAP B
formation O
is O
a O
requisite O
step O
in O
APAP B
- O
induced O
nephrotoxicity O
. O

Therefore O
, O
the O
effect O
of O
bis B
( I
p I
- I
nitrophenyl I
) I
phosphate I
( O
BNPP B
) O
, O
an O
acylamidase O
inhibitor O
, O
on O
APAP B
and O
PAP B
nephrotoxicity O
and O
metabolism O
was O
determined O
. O

BNPP B
( O
1 O
to O
8 O
mM O
) O
reduced O
APAP B
deacetylation O
and O
covalent O
binding O
in O
F344 O
renal O
cortical O
homogenates O
in O
a O
concentration O
- O
dependent O
manner O
. O

Pretreatment O
of O
animals O
with O
BNPP B
prior O
to O
APAP B
or O
PAP B
administration O
resulted O
in O
marked O
reduction O
of O
APAP B
( O
900 O
mg O
/ O
kg O
) O
nephrotoxicity O
but O
not O
PAP B
nephrotoxicity O
. O

This O
result O
was O
not O
due O
to O
altered O
disposition O
of O
either O
APAP B
or O
acetylated O
metabolites O
in O
plasma O
or O
renal O
cortical O
and O
hepatic O
tissue O
. O

Rather O
, O
BNPP B
pretreatment O
reduced O
the O
fraction O
of O
APAP B
excreted O
as O
PAP B
by O
64 O
and O
75 O
% O
after O
APAP B
doses O
of O
750 O
and O
900 O
mg O
/ O
kg O
. O

BNPP B
did O
not O
alter O
the O
excretion O
of O
APAP B
or O
any O
of O
its O
non O
- O
deacetylated O
metabolites O
nor O
did O
BNPP B
alter O
excretion O
of O
PAP B
or O
its O
metabolites O
after O
PAP B
doses O
of O
150 O
and O
300 O
mg O
/ O
kg O
. O

Therefore O
, O
the O
BNPP O
- O
induced O
reduction O
in O
APAP B
- O
induced O
nephrotoxicity O
appears O
to O
be O
due O
to O
inhibition O
of O
APAP B
deacetylation O
. O

It O
is O
concluded O
that O
PAP B
formation O
, O
in O
vivo O
, O
accounts O
, O
at O
least O
in O
part O
, O
for O
APAP B
- O
induced O
renal O
tubular O
necrosis O
. O

Morphine B
- O
induced O
seizures O
in O
newborn O
infants O
. O

Two O
neonates O
suffered O
from O
generalized O
seizures O
during O
the O
course O
of O
intravenous O
morphine B
sulfate I
for O
post O
- O
operative O
analgesia O
. O

They O
received O
morphine B
in O
doses O
of O
32 O
micrograms O
/ O
kg O
/ O
hr O
and O
40 O
micrograms O
/ O
kg O
/ O
hr O
larger O
than O
a O
group O
of O
10 O
neonates O
who O
received O
6 O
- O
24 O
micrograms O
/ O
kg O
/ O
hr O
and O
had O
no O
seizures O
. O

Plasma O
concentrations O
of O
morphine B
in O
these O
neonates O
was O
excessive O
( O
60 O
and O
90 O
mg O
/ O
ml O
) O
. O

Other O
known O
reasons O
for O
seizures O
were O
ruled O
out O
and O
the O
convulsions O
stopped O
a O
few O
hours O
after O
cessation O
of O
morphine B
and O
did O
not O
reoccur O
in O
the O
subsequent O
8 O
months O
. O

It O
is O
suggested O
that O
post O
- O
operative O
intravenous O
morphine B
should O
not O
exceed O
20 O
micrograms O
/ O
kg O
/ O
ml O
in O
neonates O
. O

Indomethacin B
induced O
hypotension O
in O
sodium B
and O
volume O
depleted O
rats O
. O

After O
a O
single O
oral O
dose O
of O
4 O
mg O
/ O
kg O
indomethacin B
( O
IDM O
) O
to O
sodium B
and O
volume O
depleted O
rats O
plasma O
renin O
activity O
( O
PRA O
) O
and O
systolic O
blood O
pressure O
fell O
significantly O
within O
four O
hours O
. O

In O
sodium B
repleted O
animals O
indomethacin B
did O
not O
change O
systolic O
blood O
pressure O
( O
BP O
) O
although O
plasma O
renin O
activity O
was O
decreased O
. O

Thus O
, O
indomethacin B
by O
inhibition O
of O
prostaglandin B
synthesis O
may O
diminish O
the O
blood O
pressure O
maintaining O
effect O
of O
the O
stimulated O
renin O
- O
angiotensin B
system O
in O
sodium B
and O
volume O
depletion O
. O

On O
the O
antiarrhythmic O
activity O
of O
one O
N B
- I
substituted I
piperazine I
derivative O
of O
trans B
- I
2 I
- I
amino I
- I
3 I
- I
hydroxy I
- I
1 I
, I
2 I
, I
3 I
, I
4 I
- I
tetrahydroanaphthalene I
. O

The O
antiarrhythmic O
activity O
of O
the O
compound O
N B
- I
( I
trans I
- I
3 I
- I
hydroxy I
- I
1 I
, I
2 I
, I
3 I
, I
4 I
- I
tetrahydro I
- I
2 I
- I
naphthyl I
) I
- I
N I
- I
( I
3 I
- I
oxo I
- I
3 I
- I
phenyl I
- I
2 I
- I
methylpropyl I
) I
- I
piperazine I
hydrochloride I
, O
referred O
to O
as O
P11 O
, O
is O
studied O
on O
anaesthesized O
cats O
and O
Wistar O
albino O
rats O
, O
as O
well O
as O
on O
non O
- O
anaesthesized O
rabbits O
. O

Four O
types O
of O
experimental O
arrhythmia O
are O
used O
- O
- O
with O
BaCl2 B
, O
with O
chloroform B
- O
adrenaline B
, O
with O
strophantine B
G I
and O
with O
aconitine B
. O

The O
compound O
P11 O
is O
introduced O
in O
doses O
of O
0 O
. O
25 O
and O
0 O
. O
50 O
mg O
/ O
kg O
intravenously O
and O
10 O
mg O
/ O
kg O
orally O
. O

The O
compound O
manifests O
antiarrhythmic O
activity O
in O
all O
models O
of O
experimental O
arrhythmia O
used O
, O
causing O
greatest O
inhibition O
on O
the O
arrhythmia O
induced O
by O
chloroform B
- O
adrenaline B
( O
in O
90 O
per O
cent O
) O
and O
with O
BaCl2 B
( O
in O
84 O
per O
cent O
) O
. O

The O
results O
obtained O
are O
associated O
with O
the O
beta O
- O
adrenoblocking O
and O
with O
the O
membrane O
- O
stabilizing O
action O
of O
the O
compound O
. O

Recurrent O
subarachnoid O
hemorrhage O
associated O
with O
aminocaproic B
acid I
therapy O
and O
acute O
renal O
artery O
thrombosis O
. O

Case O
report O
. O

Epsilon B
aminocaproic I
acid I
( O
EACA B
) O
has O
been O
used O
to O
prevent O
rebleeding O
in O
patients O
with O
subarachnoid O
hemorrhage O
( O
SAH O
) O
. O

Although O
this O
agent O
does O
decrease O
the O
frequency O
of O
rebleeding O
, O
several O
reports O
have O
described O
thrombotic O
complications O
of O
EACA B
therapy O
. O

These O
complications O
have O
included O
clinical O
deterioration O
and O
intracranial O
vascular O
thrombosis O
in O
patients O
with O
SAH O
, O
arteriolar O
and O
capillary O
fibrin O
thrombi O
in O
patients O
with O
fibrinolytic O
syndromes O
treated O
with O
EACA B
, O
or O
other O
thromboembolic O
phenomena O
. O

Since O
intravascular O
fibrin O
thrombi O
are O
often O
observed O
in O
patients O
with O
fibrinolytic O
disorders O
, O
EACA B
should O
not O
be O
implicated O
in O
the O
pathogenesis O
of O
fibrin O
thrombi O
in O
patients O
with O
disseminated O
intravascular O
coagulation O
or O
other O
" O
consumption O
coagulopathies O
. O
" O
This O
report O
describes O
subtotal O
infarction O
of O
the O
kidney O
due O
to O
thrombosis O
of O
a O
normal O
renal O
artery O
. O

This O
occlusion O
occurred O
after O
EACA B
therapy O
in O
a O
patient O
with O
SAH O
and O
histopathological O
documentation O
of O
recurrent O
SAH O
. O

The O
corresponding O
clinical O
event O
was O
characterized O
by O
marked O
hypertension O
and O
abrupt O
neurological O
deterioration O
. O

Effect O
of O
vincristine B
sulfate I
on O
Pseudomonas O
infections O
in O
monkeys O
. O

In O
rhesus O
monkeys O
, O
intravenous O
challenge O
with O
0 O
. O
6 O
x O
10 O
( O
10 O
) O
to O
2 O
. O
2 O
x O
10 O
( O
10 O
) O
Pseudomonas B
aeruginosa O
organisms O
caused O
acute O
illness O
of O
4 O
to O
5 O
days O
' O
duration O
with O
spontaneous O
recovery O
in O
13 O
of O
15 O
monkeys O
; O
blood O
cultures O
became O
negative O
3 O
to O
17 O
days O
after O
challenge O
. O

Leukocytosis O
was O
observed O
in O
all O
monkeys O
. O

Intravenous O
or O
intratracheal O
inoculation O
of O
2 O
. O
0 O
to O
2 O
. O
5 O
mg O
of O
vincristine B
sulfate I
was O
followed O
by O
leukopenia O
in O
4 O
to O
5 O
days O
. O

Intravenous O
inoculation O
of O
4 O
. O
2 O
x O
10 O
( O
10 O
) O
to O
7 O
. O
8 O
x O
10 O
( O
10 O
) O
pyocin O
type O
6 O
Pseudomonas O
organisms O
in O
monkeys O
given O
vincristine B
sulfate I
4 O
days O
previously O
resulted O
in O
fatal O
infection O
in O
11 O
of O
14 O
monkeys O
, O
whereas O
none O
of O
four O
receiving O
Pseudomonas B
alone O
died O
. O

These O
studies O
suggest O
that O
an O
antimetabolite O
- O
induced O
leukopenia O
predisposes O
to O
severe O
Pseudomonas O
sepsis O
and O
that O
such O
monkeys O
may O
serve O
as O
a O
biological O
model O
for O
study O
of O
comparative O
efficacy O
of O
antimicrobial O
agents O
. O

Modification O
by O
propranolol B
of O
cardiovascular O
effects O
of O
induced O
hypoglycaemia O
. O

The O
cardiovascular O
effects O
of O
hypoglycaemia O
, O
with O
and O
without O
beta O
- O
blockade O
, O
were O
compared O
in O
fourteen O
healthy O
men O
. O

Eight O
received O
insulin O
alone O
, O
and O
eight O
, O
including O
two O
of O
the O
original O
insulin O
- O
only O
group O
, O
were O
given O
propranolol B
and O
insulin O
. O

In O
the O
insulin O
- O
group O
the O
period O
of O
hypoglycaemia O
was O
associated O
with O
an O
increase O
in O
heart O
- O
rate O
and O
a O
fall O
in O
diastolic O
blood O
- O
pressure O
. O

In O
the O
propranolol B
- O
insulin O
group O
there O
was O
a O
significant O
fall O
in O
heart O
- O
rate O
in O
most O
subjects O
and O
an O
increase O
in O
diastolic O
pressure O
. O

Typical O
S O
- O
T O
/ O
T O
changes O
occurred O
in O
the O
insulin O
- O
group O
but O
in O
none O
of O
the O
propranolol B
- O
insulin O
group O
. O

Hypertension O
in O
diabetics O
prone O
to O
hypoglycaemia O
attacks O
should O
not O
be O
treated O
with O
beta O
- O
blockers O
because O
these O
drugs O
may O
cause O
a O
sharp O
rise O
in O
blood O
- O
pressure O
in O
such O
patients O
. O

Long O
- O
term O
propranolol B
therapy O
in O
pregnancy O
: O
maternal O
and O
fetal O
outcome O
. O

Propranolol B
, O
a O
beta O
- O
adrenergic O
blocking O
agent O
, O
has O
found O
an O
important O
position O
in O
the O
practice O
of O
medicine O
. O

Its O
use O
in O
pregnancy O
, O
however O
, O
is O
an O
open O
question O
as O
a O
number O
of O
detrimental O
side O
effects O
have O
been O
reported O
in O
the O
fetus O
and O
neonate O
. O

Ten O
patients O
and O
12 O
pregnancies O
are O
reported O
where O
chronic O
propranolol B
has O
been O
administered O
. O

Five O
patients O
with O
serial O
pregnancies O
with O
and O
without O
propranolol B
therapy O
are O
also O
examined O
. O

Maternal O
, O
fetal O
, O
and O
neonatal O
complications O
are O
examined O
. O

An O
attempt O
is O
made O
to O
differentiate O
drug O
- O
related O
complications O
from O
maternal O
disease O
- O
- O
related O
complications O
. O

We O
conclude O
that O
previously O
reported O
hypoglycemia O
, O
hyperbilirubinemia O
, O
polycythemia O
, O
neonatal O
apnea O
, O
and O
bradycardia O
are O
not O
invariable O
and O
cannot O
be O
statistically O
correlated O
with O
chronic O
propranolol B
therapy O
. O

Growth O
retardation O
, O
however O
, O
appears O
to O
be O
significant O
in O
both O
of O
our O
series O
. O

Central O
excitatory O
actions O
of O
flurazepam B
. O

Toxic O
actions O
of O
flurazepam B
( O
FZP B
) O
were O
studied O
in O
cats O
, O
mice O
and O
rats O
. O

High O
doses O
caused O
an O
apparent O
central O
excitation O
, O
most O
clearly O
seen O
as O
clonic O
convulsions O
, O
superimposed O
on O
general O
depression O
. O

Following O
a O
lethal O
dose O
, O
death O
was O
always O
associated O
with O
convulsions O
. O

Comparing O
the O
relative O
sensitivity O
to O
central O
depression O
and O
excitation O
revealed O
that O
rats O
were O
least O
likely O
to O
have O
convulsions O
at O
doses O
that O
did O
not O
first O
cause O
loss O
of O
consciousness O
, O
while O
cats O
most O
clearly O
showed O
marked O
central O
excitatory O
actions O
. O

Signs O
of O
FZP B
toxocity O
in O
cats O
included O
excessive O
salivation O
, O
extreme O
apprehensive O
behavior O
, O
retching O
, O
muscle O
tremors O
and O
convulsions O
. O

An O
interaction O
between O
FZP B
and O
pentylenetetrazol B
( O
PTZ B
) O
was O
shown O
by O
pretreating O
mice O
with O
FZP B
before O
PTZ B
challenge O
. O

As O
a O
function O
of O
dose O
, O
FZP B
first O
protected O
against O
convulsions O
and O
death O
. O

At O
higher O
doses O
, O
however O
, O
convulsions O
again O
emerged O
. O

These O
doses O
of O
FZP B
were O
lower O
than O
those O
that O
would O
alone O
cause O
convulsions O
. O

These O
results O
may O
be O
relevant O
to O
the O
use O
of O
FZP B
in O
clinical O
situations O
in O
which O
there O
is O
increased O
neural O
excitability O
, O
such O
as O
epilepsy O
or O
sedative O
- O
hypnotic O
drug O
withdrawal O
. O

Use O
of O
propranolol B
in O
the O
treatment O
of O
idiopathic O
orthostatic O
hypotension O
. O

Five O
patients O
with O
idiopathic O
orthostatic O
hypotension O
who O
had O
physiologic O
and O
biochemical O
evidence O
of O
severe O
autonomic O
dysfunction O
were O
included O
in O
the O
study O
. O

They O
all O
exhibited O
markedly O
reduced O
plasma O
catecholamines B
and O
plasma O
renin O
activity O
in O
both O
recumbent O
and O
upright O
positions O
and O
had O
marked O
hypersensitivity O
to O
the O
pressor O
effects O
of O
infused O
norepinephrine B
. O

Treatment O
with O
propanolol B
administered O
intravenously O
( O
1 O
- O
5 O
mg O
) O
produced O
increases O
in O
supine O
and O
upright O
blood O
pressure O
in O
4 O
of O
the O
5 O
individuals O
with O
rises O
ranging O
from O
11 O
/ O
6 O
to O
22 O
/ O
11 O
mmHg O
. O

Chronic O
oral O
administration O
of O
propranolol B
( O
40 O
- O
160 O
mg O
/ O
day O
) O
also O
elevated O
the O
blood O
pressures O
of O
these O
individuals O
with O
increases O
in O
the O
order O
of O
20 O
- O
35 O
/ O
15 O
- O
25 O
mmg O
being O
observed O
. O

In O
1 O
patient O
, O
marked O
hypertension O
was O
induced O
by O
propranolol B
and O
the O
drug O
had O
to O
be O
withdrawn O
. O

It O
otherwise O
was O
well O
tolerated O
and O
no O
important O
side O
effects O
were O
observed O
. O

Treatment O
has O
been O
continued O
in O
3 O
individuals O
for O
6 O
- O
13 O
months O
with O
persistence O
of O
the O
pressor O
effect O
, O
although O
there O
appears O
to O
have O
been O
some O
decrease O
in O
the O
degree O
of O
response O
with O
time O
. O

Hemodynamic O
measurements O
in O
1 O
of O
the O
patients O
demonstrated O
an O
increase O
in O
total O
peripheral O
resistance O
and O
essentially O
no O
change O
in O
cardiac O
output O
following O
propranolol B
therapy O
. O

The O
studies O
suggest O
that O
propranolol B
is O
a O
useful O
drug O
in O
selected O
patients O
with O
severe O
idiopathic O
orthostatic O
hypotension O
. O

Total O
intravenous O
anesthesia O
with O
etomidate B
. O

III O
. O

Some O
observations O
in O
adults O
. O

An O
investigation O
was O
undertaken O
to O
determine O
the O
dosage O
of O
etomidate B
required O
to O
maintain O
sleep O
in O
adults O
undergoing O
surgery O
under O
regional O
local O
anesthesia O
. O

Premedication O
of O
diazepam B
10 O
mg O
and O
atropine B
0 O
. O
5 O
mg O
was O
given O
, O
and O
sleep O
was O
induced O
and O
maintained O
by O
intermittent O
intravenous O
injections O
of O
etomidate B
0 O
. O
1 O
/ O
mg O
/ O
kg O
, O
given O
whenever O
the O
patient O
would O
open O
his O
eyes O
on O
request O
. O

A O
mean O
overall O
dose O
of O
etomidate B
17 O
. O
4 O
microgram O
/ O
kg O
/ O
min O
. O
was O
required O
to O
maintain O
sleep O
, O
but O
great O
individual O
variation O
occurred O
, O
with O
older O
patients O
requiring O
less O
drug O
. O

The O
investigation O
was O
discontinued O
after O
18 O
patients O
because O
of O
the O
frequency O
and O
intensity O
of O
side O
- O
effects O
, O
particularly O
pain O
and O
myoclonia O
, O
which O
caused O
the O
technique O
to O
be O
abandoned O
in O
two O
cases O
. O

It O
is O
considered O
unlikely O
that O
etomidate B
will O
prove O
to O
be O
the O
hypnotic O
of O
choice O
for O
a O
totally O
intravenous O
anesthetic O
technique O
in O
adults O
because O
of O
the O
high O
incidence O
of O
myoclonia O
after O
prolonged O
administration O
. O

In O
several O
patients O
uncontrollable O
muscle O
movements O
persisted O
for O
many O
minutes O
after O
complete O
recovery O
of O
consciousness O
. O

Evidence O
for O
cardiac O
beta O
2 O
- O
adrenoceptors O
in O
man O
. O

We O
compared O
the O
effects O
of O
single O
doses O
of O
50 O
mg O
atenolol B
( O
cardioselective O
) O
, O
40 O
mg O
propranolol B
( O
nonselective O
) O
, O
and O
placebo O
on O
both O
exercise O
- O
and O
isoproterenol B
- O
induced O
tachycardia O
in O
two O
experiments O
involving O
nine O
normal O
subjects O
. O

Maximal O
exercise O
heart O
rate O
was O
reduced O
from O
187 O
+ O
/ O
- O
4 O
( O
SEM O
) O
after O
placebo O
to O
146 O
+ O
/ O
- O
7 O
bpm O
after O
atenolol B
and O
138 O
+ O
/ O
- O
6 O
bpm O
after O
propranolol B
, O
but O
there O
were O
no O
differences O
between O
the O
drugs O
. O

The O
effects O
on O
isoproterenol B
tachycardia O
were O
determined O
before O
and O
after O
atropine B
( O
0 O
. O
04 O
mg O
/ O
kg O
IV O
) O
. O

Isoproterenol B
sensitivity O
was O
determined O
as O
the O
intravenous O
dose O
that O
increased O
heart O
rate O
by O
25 O
bpm O
( O
CD25 O
) O
and O
this O
was O
increased O
from O
1 O
. O
8 O
+ O
/ O
- O
0 O
. O
3 O
micrograms O
after O
placebo O
to O
38 O
. O
9 O
+ O
/ O
- O
8 O
. O
3 O
micrograms O
after O
propranolol B
and O
8 O
. O
3 O
+ O
/ O
- O
1 O
. O
7 O
micrograms O
after O
atenolol B
. O

The O
difference O
in O
the O
effects O
of O
the O
two O
was O
significant O
. O

After O
atropine B
the O
CD25 O
was O
unchanged O
after O
placebo O
( O
2 O
. O
3 O
+ O
/ O
- O
0 O
. O
3 O
micrograms O
) O
and O
atenolol B
( O
7 O
. O
7 O
+ O
/ O
- O
1 O
. O
3 O
micrograms O
) O
; O
it O
was O
reduced O
after O
propranolol B
( O
24 O
. O
8 O
+ O
/ O
- O
5 O
. O
0 O
micrograms O
) O
, O
but O
remained O
different O
from O
atenolol B
. O

This O
change O
with O
propranolol B
sensitivity O
was O
calculated O
as O
the O
apparent O
Ka O
, O
this O
was O
unchanged O
by O
atropine B
( O
11 O
. O
7 O
+ O
/ O
- O
2 O
. O
1 O
and O
10 O
. O
1 O
+ O
/ O
- O
2 O
. O
5 O
ml O
/ O
ng O
) O
. O

These O
data O
are O
consistent O
with O
the O
hypothesis O
that O
exercise O
- O
induced O
tachycardia O
results O
largely O
from O
beta O
1 O
- O
receptor O
activation O
that O
is O
blocked O
by O
both O
cardioselective O
and O
nonselective O
drugs O
, O
whereas O
isoproterenol B
activates O
both O
beta O
1 O
- O
and O
beta O
2 O
- O
receptors O
so O
that O
after O
cardioselective O
blockade O
there O
remains O
a O
beta O
2 O
- O
component O
that O
can O
be O
blocked O
with O
a O
nonselective O
drug O
. O

While O
there O
appear O
to O
be O
beta O
2 O
- O
receptors O
in O
the O
human O
heart O
, O
their O
physiologic O
or O
pathologic O
roles O
remain O
to O
be O
defined O
. O

Hormones O
and O
risk O
of O
breast O
cancer O
. O

This O
paper O
reports O
the O
results O
of O
a O
study O
of O
50 O
menopausal O
women O
receiving O
hormonal O
replacement O
therapy O
. O

The O
majority O
( O
29 O
) O
had O
surgical O
menopause O
; O
their O
mean O
age O
was O
45 O
. O
7 O
years O
. O

It O
was O
hypothesized O
that O
progestins B
could O
equilibrate O
the O
effects O
of O
the O
estrogenic O
stimulation O
on O
the O
mammary O
and O
endometrial O
target O
tissues O
of O
women O
on O
hormonal O
replacement O
therapy O
. O

The O
treatment O
schedule O
consisted O
of O
conjugated O
estrogens I
( O
Premarin B
) O
1 O
. O
25 O
mg O
/ O
day O
for O
21 O
days O
and O
Medroxyprogesterone B
acetate I
10 O
mg O
/ O
day O
for O
10 O
days O
in O
each O
month O
. O

The O
mean O
treatment O
period O
was O
18 O
months O
. O

During O
the O
follow O
- O
up O
period O
, O
attention O
was O
paid O
to O
breast O
modifications O
as O
evidenced O
by O
symptomatology O
, O
physical O
examination O
, O
and O
plate O
thermography O
. O

Mastodynia O
was O
reported O
by O
21 O
patients O
, O
and O
physical O
examination O
revealed O
a O
light O
increase O
in O
breast O
firmness O
in O
12 O
women O
and O
a O
moderate O
increase O
in O
breast O
nodularity O
in O
2 O
women O
. O

Themography O
confirmed O
the O
existence O
of O
an O
excessive O
breast O
stimulation O
in O
1 O
women O
who O
complained O
of O
moderate O
mastodynia O
and O
in O
5 O
of O
the O
7 O
women O
who O
complained O
of O
severe O
mastodynia O
. O

Normalization O
was O
obtained O
by O
halving O
the O
estrogen B
dose O
. O

These O
results O
suggest O
that O
hormonal O
replacement O
therapy O
can O
be O
safely O
prescribed O
if O
the O
following O
criteria O
are O
satisfied O
: O
1 O
) O
preliminary O
evaluation O
of O
patients O
from O
a O
clinical O
, O
metabolic O
, O
cytologic O
, O
and O
mammographic O
perspective O
; O
2 O
) O
cyclic O
treatment O
schedule O
, O
with O
a O
progestative O
phase O
of O
10 O
days O
; O
and O
3 O
) O
periodic O
complete O
follow O
- O
up O
, O
with O
accurate O
thermographic O
evaluation O
of O
the O
breast O
target O
tissues O
. O

Early O
infections O
in O
kidney O
, O
heart O
, O
and O
liver O
transplant O
recipients O
on O
cyclosporine B
. O

Eighty O
- O
one O
renal O
, O
seventeen O
heart O
, O
and O
twenty O
- O
four O
liver O
transplant O
patients O
were O
followed O
for O
infection O
. O

Seventeen O
renal O
patients O
received O
azathioprine B
( O
Aza B
) O
and O
prednisone B
as O
part O
of O
a O
randomized O
trial O
of O
immunosuppression O
with O
21 O
cyclosporine B
- O
and O
- O
prednisone B
- O
treated O
renal O
transplant O
patients O
. O

All O
others O
received O
cyclosporine B
and O
prednisone B
. O

The O
randomized O
Aza B
patients O
had O
more O
overall O
infections O
( O
P O
less O
than O
0 O
. O
05 O
) O
and O
more O
nonviral O
infections O
( O
P O
less O
than O
0 O
. O
02 O
) O
than O
the O
randomized O
cyclosporine B
patients O
. O

Heart O
and O
liver O
patients O
had O
more O
infections O
than O
cyclosporine B
renal O
patients O
but O
fewer O
infections O
than O
the O
Aza B
renal O
patients O
. O

There O
were O
no O
infectious O
deaths O
in O
renal O
transplant O
patients O
on O
cyclosporine B
or O
Aza B
, O
but O
infection O
played O
a O
major O
role O
in O
3 O
out O
of O
6 O
cardiac O
transplant O
deaths O
and O
in O
8 O
out O
of O
9 O
liver O
transplant O
deaths O
. O

Renal O
patients O
on O
cyclosporine B
had O
the O
fewest O
bacteremias O
. O

Analysis O
of O
site O
of O
infection O
showed O
a O
preponderance O
of O
abdominal O
infections O
in O
liver O
patients O
, O
intrathoracic O
infections O
in O
heart O
patients O
, O
and O
urinary O
tract O
infections O
in O
renal O
patients O
. O

Pulmonary O
infections O
were O
less O
common O
in O
cyclosporine B
- O
treated O
renal O
patients O
than O
in O
Aza B
- O
treated O
patients O
( O
P O
less O
than O
0 O
. O
05 O
) O
. O

Aza B
patients O
had O
significantly O
more O
staphylococcal O
infections O
than O
all O
other O
transplant O
groups O
( O
P O
less O
than O
0 O
. O
005 O
) O
, O
and O
systemic O
fungal O
infections O
occurred O
only O
in O
the O
liver O
transplant O
group O
. O

Cytomegalovirus O
( O
CMV O
) O
shedding O
or O
serological O
rises O
in O
antibody O
titer O
, O
or O
both O
occurred O
in O
78 O
% O
of O
cyclosporine B
patients O
and O
76 O
% O
of O
Aza B
patients O
. O

Of O
the O
cyclosporine B
patients O
, O
15 O
% O
had O
symptoms O
related O
to O
CMV O
infection O
. O

Serological O
evidence O
for O
Epstein O
Barr O
Virus O
infection O
was O
found O
in O
20 O
% O
of O
65 O
cyclosporine B
patients O
studied O
. O

Three O
had O
associated O
symptoms O
, O
and O
one O
developed O
a O
lymphoma O
. O

Structure O
- O
activity O
and O
dose O
- O
effect O
relationships O
of O
the O
antagonism O
of O
picrotoxin B
- O
induced O
seizures O
by O
cholecystokinin B
, O
fragments O
and O
analogues O
of O
cholecystokinin B
in O
mice O
. O

Intraperitoneal O
administration O
of O
cholecystokinin B
octapeptide I
sulphate I
ester I
( O
CCK B
- I
8 I
- I
SE I
) O
and O
nonsulphated O
cholecystokinin B
octapeptide I
( O
CCK B
- I
8 I
- I
NS I
) O
enhanced O
the O
latency O
of O
seizures O
induced O
by O
picrotoxin B
in O
mice O
. O

Experiments O
with O
N O
- O
and O
C O
- O
terminal O
fragments O
revealed O
that O
the O
C O
- O
terminal O
tetrapeptide O
( O
CCK B
- I
5 I
- I
8 I
) O
was O
the O
active O
centre O
of O
the O
CCK B
octapeptide I
molecule O
. O

The O
analogues O
CCK B
- I
8 I
- I
SE I
and O
CCK B
- I
8 I
- I
NS I
( O
dose O
range O
0 O
. O
2 O
- O
6 O
. O
4 O
mumol O
/ O
kg O
) O
and O
caerulein B
dose O
range O
0 O
. O
1 O
- O
0 O
. O
8 O
mumol O
/ O
kg O
) O
showed O
bell O
- O
shaped O
dose O
- O
effect O
curves O
, O
with O
the O
greatest O
maximum O
inhibition O
for O
CCK B
- I
8 I
- I
NS I
. O

The O
peptide O
CCK B
- I
5 I
- I
8 I
had O
weak O
anticonvulsant O
activity O
in O
comparison O
to O
the O
octapeptides O
, O
3 O
. O
2 O
mumol O
/ O
kg O
and O
larger O
doses O
of O
the O
reference O
drug O
, O
diazepam B
, O
totally O
prevented O
picrotoxin B
- O
induced O
seizures O
and O
mortality O
. O

The O
maximum O
effect O
of O
the O
peptides O
tested O
was O
less O
than O
that O
of O
diazepam B
. O

Experiments O
with O
analogues O
and O
derivatives O
of O
CCK B
- I
5 I
- I
8 I
demonstrated O
that O
the O
effectiveness O
of O
the O
beta B
- I
alanyl I
derivatives O
of O
CCK B
- I
5 I
- I
8 I
were O
enhanced O
and O
that O
they O
were O
equipotent O
with O
CCK B
- I
8 I
- I
SE O
. O

Of O
the O
CCK B
- I
2 I
- I
8 I
analogues O
, O
Ser B
( O
SO3H O
) I
7 O
- O
Ac O
- I
CCK I
- I
2 I
- I
8 I
- I
SE I
and O
Thr B
( O
SO3H O
) I
7 I
- I
Ac I
- I
CCK I
- I
2 I
- I
8 I
- I
SE I
and O
Hyp B
( O
SO3H O
) O
- O
Ac B
- I
CCK I
- I
2 I
- I
8 I
- I
SE I
were O
slightly O
more O
active O
than O
CCK B
- I
8 I
- I
SE I
. O

Vasopressin B
as O
a O
possible O
contributor O
to O
hypertension O
. O

The O
role O
of O
vasopressin B
as O
a O
pressor O
agent O
to O
the O
hypertensive O
process O
was O
examined O
. O

Vasopressin B
plays O
a O
major O
role O
in O
the O
pathogenesis O
of O
DOCA B
- I
salt I
hypertension O
, O
since O
the O
elevation O
of O
blood O
pressure O
was O
not O
substantial O
in O
the O
rats O
with O
lithium B
- O
treated O
diabetes O
insipidus O
after O
DOCA B
- I
salt I
treatment O
. O

Administration O
of O
DDAVP O
which O
has O
antidiuretic O
action O
but O
minimal O
vasopressor O
effect O
failed O
to O
increase O
blood O
pressure O
to O
the O
levels O
observed O
after O
administration O
of O
AVP B
. O

Furthermore O
, O
the O
pressor O
action O
of O
vasopressin B
appears O
to O
be O
important O
in O
the O
development O
of O
this O
model O
of O
hypertension O
, O
since O
the O
enhanced O
pressor O
responsiveness O
to O
the O
hormone O
was O
observed O
in O
the O
initial O
stage O
of O
hypertension O
. O

Increased O
secretion O
of O
vasopressin B
from O
neurohypophysis O
also O
promotes O
the O
function O
of O
the O
hormone O
as O
a O
pathogenetic O
factor O
in O
hypertension O
. O

An O
unproportional O
release O
of O
vasopressin B
compared O
to O
plasma O
osmolality O
may O
be O
induced O
by O
the O
absence O
of O
an O
adjusting O
control O
of O
angiotensin B
II I
forming O
and O
receptor O
binding O
capacity O
for O
sodium B
balance O
in O
the O
brain O
. O

However O
, O
the O
role O
of O
vasopressin B
remains O
to O
be O
determined O
in O
human O
essential O
hypertension O
. O

Toxic O
hepatitis O
induced O
by O
disulfiram B
in O
a O
non O
- O
alcoholic O
. O

A O
reversible O
toxic O
liver O
damage O
was O
observed O
in O
a O
non O
- O
alcoholic O
woman O
treated O
with O
disulfiram B
. O

The O
causative O
relationship O
was O
proven O
by O
challenge O
. O

Atrial O
thrombosis O
involving O
the O
heart O
of O
F O
- O
344 O
rats O
ingesting O
quinacrine B
hydrochloride I
. O

Quinacrine B
hydrochloride I
is O
toxic O
for O
the O
heart O
of O
F O
- O
344 O
rats O
. O

Rats O
treated O
with O
500 O
ppm O
quinacrine B
hydrochloride I
in O
the O
diet O
all O
developed O
a O
high O
incidence O
of O
left O
atrial O
thrombosis O
. O

The O
lesion O
was O
associated O
with O
cardiac O
hypertrophy O
and O
dilatation O
and O
focal O
myocardial O
degeneration O
. O

Rats O
died O
from O
cardiac O
hypertrophy O
with O
severe O
acute O
and O
chronic O
congestion O
of O
the O
lungs O
, O
liver O
, O
and O
other O
organs O
. O

Seventy O
percent O
of O
rats O
given O
250 O
ppm O
quinacrine B
hydrochloride I
and O
1 O
, O
000 O
ppm O
sodium B
nitrite I
simultaneously O
in O
the O
diet O
had O
thrombosis O
of O
the O
atria O
of O
the O
heart O
, O
while O
untreated O
control O
rats O
in O
this O
laboratory O
did O
not O
have O
atrial O
thrombosis O
. O

Sodium B
nitrite I
in O
combination O
with O
quinacrine B
hydrochloride I
appeared O
to O
have O
no O
additional O
effect O
. O

Alternating O
sinus O
rhythm O
and O
intermittent O
sinoatrial O
block O
induced O
by O
propranolol B
. O

Alternating O
sinus O
rhythm O
and O
intermittent O
sinoatrial O
( O
S O
- O
A O
) O
block O
was O
observed O
in O
a O
57 O
- O
year O
- O
old O
woman O
, O
under O
treatment O
for O
angina O
with O
80 O
mg O
propranolol B
daily O
. O

The O
electrocardiogram O
showed O
alternation O
of O
long O
and O
short O
P O
- O
P O
intervals O
and O
occasional O
pauses O
. O

These O
pauses O
were O
always O
preceded O
by O
the O
short O
P O
- O
P O
intervals O
and O
were O
usually O
followed O
by O
one O
or O
two O
P O
- O
P O
intervals O
of O
0 O
. O
92 O
- O
0 O
. O
95 O
s O
representing O
the O
basic O
sinus O
cycle O
. O

Following O
these O
basic O
sinus O
cycles O
, O
alternating O
rhythm O
started O
with O
the O
longer O
P O
- O
P O
interval O
. O

The O
long O
P O
- O
P O
intervals O
ranged O
between O
1 O
. O
04 O
- O
1 O
. O
12 O
s O
and O
the O
short O
P O
- O
P O
intervals O
between O
0 O
. O
80 O
- O
0 O
. O
84 O
s O
, O
respectively O
. O

The O
duration O
of O
the O
pauses O
were O
equal O
or O
almost O
equal O
to O
one O
short O
plus O
one O
long O
P O
- O
P O
interval O
or O
to O
twice O
the O
basic O
sinus O
cycle O
. O

In O
one O
recording O
a O
short O
period O
of O
regular O
sinus O
rhythm O
with O
intermittent O
2 O
/ O
1 O
S O
- O
A O
block O
was O
observed O
. O

This O
short O
period O
of O
sinus O
rhythm O
was O
interrupted O
by O
sudden O
prolongation O
of O
the O
P O
- O
P O
interval O
starting O
the O
alternative O
rhythm O
. O

There O
were O
small O
changes O
in O
the O
shape O
of O
the O
P O
waves O
and O
P O
- O
R O
intervals O
. O

S O
- O
A O
conduction O
through O
two O
pathways O
, O
the O
first O
with O
2 O
/ O
1 O
block O
the O
second O
having O
0 O
. O
12 O
- O
0 O
. O
14 O
s O
longer O
conduction O
time O
and O
with O
occasional O
2 O
/ O
1 O
block O
was O
proposed O
for O
the O
explanation O
of O
the O
alternating O
P O
- O
P O
interval O
and O
other O
electrocardiographic O
features O
seen O
. O

Atropine B
1 O
mg O
given O
intravenously O
resulted O
in O
shortening O
of O
all O
P O
- O
P O
intervals O
without O
changing O
the O
rhythm O
. O

The O
abnormal O
rhythm O
disappeared O
with O
the O
withdrawal O
of O
propranolol B
and O
when O
the O
drug O
was O
restarted O
a O
2 O
/ O
1 O
S O
- O
A O
block O
was O
seen O
. O

This O
was O
accepted O
as O
evidence O
for O
propranolol B
being O
the O
cause O
of O
this O
conduction O
disorder O
. O

Antitumor O
effect O
, O
cardiotoxicity O
, O
and O
nephrotoxicity O
of O
doxorubicin B
in O
the O
IgM O
solid O
immunocytoma O
- O
bearing O
LOU O
/ O
M O
/ O
WSL O
rat O
. O

Antitumor O
activity O
, O
cardiotoxicity O
, O
and O
nephrotoxicity O
induced O
by O
doxorubicin B
were O
studied O
in O
LOU O
/ O
M O
/ O
WSL O
inbred O
rats O
each O
bearing O
a O
transplantable O
solid O
IgM O
immunocytoma O
. O

Animals O
with O
a O
tumor O
( O
diameter O
, O
15 O
. O
8 O
+ O
/ O
- O
3 O
. O
3 O
mm O
) O
were O
treated O
with O
iv O
injections O
of O
doxorubicin B
on O
5 O
consecutive O
days O
, O
followed O
by O
1 O
weekly O
injection O
for O
7 O
weeks O
( O
dose O
range O
, O
0 O
. O
015 O
- O
4 O
. O
0 O
mg O
/ O
kg O
body O
wt O
) O
. O

Tumor O
regression O
was O
observed O
with O
0 O
. O
5 O
mg O
doxorubicin B
/ O
kg O
. O

Complete O
disappearance O
of O
the O
tumor O
was O
induced O
with O
1 O
. O
0 O
mg O
doxorubicin B
/ O
kg O
. O

Histologic O
evidence O
of O
cardiotoxicity O
scored O
as O
grade O
III O
was O
only O
observed O
at O
a O
dose O
of O
1 O
. O
0 O
mg O
doxorubicin B
/ O
kg O
. O

Light O
microscopic O
evidence O
of O
renal O
damage O
was O
seen O
above O
a O
dose O
of O
0 O
. O
5 O
mg O
doxorubicin B
/ O
kg O
, O
which O
resulted O
in O
albuminuria O
and O
very O
low O
serum O
albumin O
levels O
. O

In O
the O
group O
that O
received O
1 O
. O
0 O
mg O
doxorubicin B
/ O
kg O
, O
the O
serum O
albumin O
level O
decreased O
from O
33 O
. O
6 O
+ O
/ O
- O
4 O
. O
1 O
to O
1 O
. O
5 O
+ O
/ O
- O
0 O
. O
5 O
g O
/ O
liter O
. O

Ascites O
and O
hydrothorax O
were O
observed O
simultaneously O
. O

The O
same O
experiments O
were O
performed O
with O
non O
- O
tumor O
- O
bearing O
rats O
, O
in O
which O
no O
major O
differences O
were O
observed O
. O

In O
conclusion O
, O
antitumor O
activity O
, O
cardiotoxicity O
, O
and O
nephrotoxicity O
were O
studied O
simultaneously O
in O
the O
same O
LOU O
/ O
M O
/ O
WSL O
rat O
. O

Albuminuria O
due O
to O
renal O
damage O
led O
to O
extremely O
low O
serum O
albumin O
levels O
, O
so O
ascites O
and O
hydrothorax O
were O
not O
necessarily O
a O
consequence O
of O
the O
observed O
cardiomyopathy O
. O

Intraoperative O
bradycardia O
and O
hypotension O
associated O
with O
timolol B
and O
pilocarpine B
eye O
drops O
. O

A O
69 O
- O
yr O
- O
old O
man O
, O
who O
was O
concurrently O
being O
treated O
with O
pilocarpine B
nitrate I
and O
timolol B
maleate I
eye O
drops O
, O
developed O
a O
bradycardia O
and O
became O
hypotensive O
during O
halothane B
anaesthesia O
. O

Both O
timolol B
and O
pilocarpine B
were O
subsequently O
identified O
in O
a O
24 O
- O
h O
collection O
of O
urine O
. O

Timolol B
( O
but O
not O
pilocarpine B
) O
was O
detected O
in O
a O
sample O
of O
plasma O
removed O
during O
surgery O
; O
the O
plasma O
concentration O
of O
timolol B
( O
2 O
. O
6 O
ng O
ml O
- O
1 O
) O
was O
consistent O
with O
partial O
beta O
- O
adrenoceptor O
blockade O
. O

It O
is O
postulated O
that O
this O
action O
may O
have O
been O
enhanced O
during O
halothane B
anaesthesia O
with O
resultant O
bradycardia O
and O
hypotension O
. O

Pilocarpine B
may O
have O
had O
a O
contributory O
effect O
. O

Succinylcholine B
apnoea O
: O
attempted O
reversal O
with O
anticholinesterases O
. O

Anticholinesterases O
were O
administered O
in O
an O
attempt O
to O
antagonize O
prolonged O
neuromuscular O
blockade O
following O
the O
administration O
of O
succinylcholine B
in O
a O
patient O
later O
found O
to O
be O
homozygous O
for O
atypical O
plasma O
cholinesterase O
. O

Edrophonium B
10 O
mg O
, O
given O
74 O
min O
after O
succinylcholine B
, O
when O
train O
- O
of O
- O
four O
stimulation O
was O
characteristic O
of O
phase O
II O
block O
, O
produced O
partial O
antagonism O
which O
was O
not O
sustained O
. O

Repeated O
doses O
of O
edrophonium B
to O
70 O
mg O
and O
neostigmine B
to O
2 O
. O
5 O
mg O
did O
not O
antagonize O
or O
augment O
the O
block O
. O

Spontaneous O
respiration O
recommenced O
200 O
min O
after O
succinylcholine B
administration O
. O

It O
is O
concluded O
that O
anticholinesterases O
are O
only O
partially O
effective O
in O
restoring O
neuromuscular O
function O
in O
succinylcholine B
apnoea O
despite O
muscle O
twitch O
activity O
typical O
of O
phase O
II O
block O
. O

Effect O
of O
doxorubicin B
on O
[ B
omega I
- I
I I
- I
131 I
] I
heptadecanoic B
acid I
myocardial O
scintigraphy O
and O
echocardiography O
in O
dogs O
. O

The O
effects O
of O
serial O
treatment O
with O
doxorubicin B
on O
dynamic O
myocardial O
scintigraphy O
with O
[ B
omega I
- I
I I
- I
131 I
] I
heptadecanoic I
acid I
( O
I B
- I
131 I
HA I
) O
, O
and O
on O
global O
left O
- O
ventricular O
function O
determined O
echocardiographically O
, O
were O
studied O
in O
a O
group O
of O
nine O
mongrel O
dogs O
. O

Total O
extractable O
myocardial O
lipid O
was O
compared O
postmortem O
between O
a O
group O
of O
control O
dogs O
and O
doxorubicin B
- O
treated O
dogs O
. O

A O
significant O
and O
then O
progressive O
fall O
in O
global O
LV O
function O
was O
observed O
at O
a O
cumulative O
doxorubicin B
dose O
of O
4 O
mg O
/ O
kg O
. O

A O
significant O
increase O
in O
the O
myocardial O
t1 O
/ O
2 O
of O
the O
I B
- I
131 I
HA O
was O
observed O
only O
at O
a O
higher O
cumulative O
dose O
, O
10 O
mg O
/ O
kg O
. O

No O
significant O
alteration O
in O
total O
extractable O
myocardial O
lipids O
was O
observed O
between O
control O
dogs O
and O
those O
treated O
with O
doxorubicin B
. O

Our O
findings O
suggest O
that O
the O
changes O
leading O
to O
an O
alteration O
of O
myocardial O
dynamic O
imaging O
with O
I B
- I
131 I
HA O
are O
not O
the O
initiating O
factor O
in O
doxorubicin B
cardiotoxicity O
. O

Hemodynamics O
and O
myocardial O
metabolism O
under O
deliberate O
hypotension O
. O

An O
experimental O
study O
in O
dogs O
. O

Coronary O
blood O
flow O
, O
cardiac O
work O
and O
metabolism O
were O
studied O
in O
dogs O
under O
sodium B
nitroprusside I
( O
SNP B
) O
and O
trimetaphan B
( O
TMP B
) O
deliberate O
hypotension O
( O
20 O
% O
and O
40 O
% O
mean O
pressure O
decrease O
from O
baseline O
) O
. O

Regarding O
the O
effects O
of O
drug O
- O
induced O
hypotension O
on O
coronary O
blood O
flow O
, O
aortic O
and O
coronary O
sinus O
metabolic O
data O
( O
pH O
, O
pO2 B
, O
pCO2 O
) O
we O
could O
confirm O
that O
nitroprusside B
hypotension O
could O
be O
safely O
used O
to O
30 O
% O
mean O
blood O
pressure O
decrease O
from O
control O
, O
trimetaphan B
hypotension O
to O
20 O
% O
mean O
blood O
pressure O
decrease O
. O

Cardiac O
work O
was O
significantly O
reduced O
during O
SNP B
hypotension O
. O

Myocardial O
O2 B
consumption O
and O
O2 B
availability O
were O
directly O
dependent O
on O
the O
coronary O
perfusion O
. O

Careful O
invasive O
monitoring O
of O
the O
blood O
pressure O
, O
blood O
gases O
and O
of O
the O
ECG O
ST O
- O
T O
segment O
is O
mandatory O
. O

Evidence O
for O
a O
selective O
brain O
noradrenergic O
involvement O
in O
the O
locomotor O
stimulant O
effects O
of O
amphetamine B
in O
the O
rat O
. O

Male O
rats O
received O
the O
noradrenaline B
neurotoxin O
DSP4 B
( O
50 O
mg O
/ O
kg O
) O
7 O
days O
prior O
to O
injection O
of O
D B
- I
amphetamine I
( O
10 O
or O
40 O
mumol O
/ O
kg O
i O
. O
p O
. O
) O
. O

The O
hyperactivity O
induced O
by O
D B
- I
amphetamine I
( O
10 O
mumol O
/ O
kg O
) O
was O
significantly O
reduced O
by O
DSP4 B
pretreatment O
. O

However O
, O
the O
increased O
rearings O
and O
the O
amphetamine B
- O
induced O
stereotypies O
were O
not O
blocked O
by O
pretreatment O
with O
DSP4 B
. O

The O
reduction O
of O
amphetamine B
hyperactivity O
induced O
by O
DSP4 B
was O
blocked O
by O
pretreatment O
with O
the O
noradrenaline B
- O
uptake O
blocking O
agent O
, O
desipramine B
, O
which O
prevents O
the O
neurotoxic O
action O
of O
DSP4 B
. O

The O
present O
results O
suggest O
a O
selective O
involvement O
of O
central O
noradrenergic O
neurones O
in O
the O
locomotor O
stimulant O
effect O
of O
amphetamine B
in O
the O
rat O
. O

Accelerated O
junctional O
rhythms O
during O
oral O
verapamil B
therapy O
. O

This O
study O
examined O
the O
frequency O
of O
atrioventricular O
( O
AV O
) O
dissociation O
and O
accelerated O
junctional O
rhythms O
in O
59 O
patients O
receiving O
oral O
verapamil B
. O

Accelerated O
junctional O
rhythms O
and O
AV O
dissociation O
were O
frequent O
in O
patients O
with O
supraventricular O
tachyarrhythmias O
, O
particularly O
AV O
nodal O
reentry O
. O

Verapamil B
administration O
to O
these O
patients O
led O
to O
an O
asymptomatic O
increase O
in O
activity O
of O
these O
junctional O
pacemakers O
. O

In O
patients O
with O
various O
chest O
pain O
syndromes O
, O
verapamil B
neither O
increased O
the O
frequency O
of O
junctional O
rhythms O
nor O
suppressed O
their O
role O
as O
escape O
rhythms O
under O
physiologically O
appropriate O
circumstances O
. O

Interstrain O
variation O
in O
acute O
toxic O
response O
to O
caffeine B
among O
inbred O
mice O
. O

Acute O
toxic O
dosage O
- O
dependent O
behavioral O
effects O
of O
caffeine B
were O
compared O
in O
adult O
males O
from O
seven O
inbred O
mouse O
strains O
( O
A O
/ O
J O
, O
BALB O
/ O
cJ O
, O
CBA O
/ O
J O
, O
C3H O
/ O
HeJ O
, O
C57BL O
/ O
6J O
, O
DBA O
/ O
2J O
, O
SWR O
/ O
J O
) O
. O

C57BL O
/ O
6J O
, O
chosen O
as O
a O
" O
prototypic O
" O
mouse O
strain O
, O
was O
used O
to O
determine O
behavioral O
responses O
to O
a O
broad O
range O
( O
5 O
- O
500 O
mg O
/ O
kg O
) O
of O
caffeine B
doses O
. O

Five O
phenotypic O
characteristics O
- O
- O
locomotor O
activity O
, O
righting O
ability O
, O
clonic O
seizure O
induction O
, O
stress O
- O
induced O
lethality O
, O
death O
without O
external O
stress O
- O
- O
were O
scored O
at O
various O
caffeine B
doses O
in O
drug O
- O
naive O
animals O
under O
empirically O
optimized O
, O
rigidly O
constant O
experimental O
conditions O
. O

Mice O
( O
n O
= O
12 O
for O
each O
point O
) O
received O
single O
IP O
injections O
of O
a O
fixed O
volume O
/ O
g O
body O
weight O
of O
physiological O
saline O
carrier O
with O
or O
without O
caffeine B
in O
doses O
ranging O
from O
125 O
- O
500 O
mg O
/ O
kg O
. O

Loss O
of O
righting O
ability O
was O
scored O
at O
1 O
, O
3 O
, O
5 O
min O
post O
dosing O
and O
at O
5 O
min O
intervals O
thereafter O
for O
20 O
min O
. O

In O
the O
same O
animals O
the O
occurrence O
of O
clonic O
seizures O
was O
scored O
as O
to O
time O
of O
onset O
and O
severity O
for O
20 O
min O
after O
drug O
administration O
. O

When O
these O
proceeded O
to O
tonic O
seizures O
, O
death O
occurred O
in O
less O
than O
20 O
min O
. O

Animals O
surviving O
for O
20 O
min O
were O
immediately O
stressed O
by O
a O
swim O
test O
in O
25 O
degrees O
C O
water O
, O
and O
death O
- O
producing O
tonic O
seizures O
were O
scored O
for O
2 O
min O
. O

In O
other O
animals O
locomotor O
activity O
was O
measured O
15 O
or O
60 O
min O
after O
caffeine B
administration O
. O

By O
any O
single O
behavioral O
criterion O
or O
a O
combination O
of O
these O
criteria O
, O
marked O
differences O
in O
response O
to O
toxic O
caffeine B
doses O
were O
observed O
between O
strains O
. O

These O
results O
indicate O
that O
behavioral O
toxicity O
testing O
of O
alkylxanthines B
in O
a O
single O
mouse O
strain O
may O
be O
misleading O
and O
suggest O
that O
toxic O
responses O
of O
the O
central O
nervous O
system O
to O
this O
class O
of O
compounds O
are O
genetically O
influenced O
in O
mammals O
. O

Treatment O
of O
ovarian O
cancer O
with O
a O
combination O
of O
cis B
- I
platinum I
, O
adriamycin B
, O
cyclophosphamide B
and O
hexamethylmelamine B
. O

During O
the O
last O
2 O
1 O
/ O
2 O
years O
, O
38 O
patients O
with O
ovarian O
cancer O
were O
treated O
with O
a O
combination O
of O
cisplatinum B
( O
CPDD B
) O
, O
50 O
mg O
/ O
m2 O
, O
adriamycin B
, O
30 O
mg O
/ O
m2 O
, O
cyclophosphamide B
, O
300 O
mg O
/ O
m2 O
, O
on O
day O
1 O
; O
and O
hexamethylmelamine B
( O
HMM B
) O
, O
6 O
mg O
/ O
kg O
daily O
, O
for O
14 O
days O
. O

Each O
course O
was O
repeated O
monthly O
. O

2 O
patients O
had O
stage O
II O
, O
14 O
stage O
III O
and O
22 O
stage O
IV O
disease O
. O

14 O
of O
the O
38 O
patients O
were O
previously O
treated O
with O
chemotherapy O
, O
1 O
with O
radiation O
, O
6 O
with O
both O
chemotherapy O
and O
radiation O
, O
and O
17 O
did O
not O
have O
any O
treatment O
before O
CPDD O
combination O
. O

31 O
of O
the O
38 O
cases O
( O
81 O
. O
5 O
% O
) O
demonstrated O
objective O
responses O
lasting O
for O
2 O
months O
or O
more O
. O

These O
responses O
were O
partial O
in O
19 O
and O
complete O
in O
12 O
cases O
. O

Hematologic O
toxicity O
was O
moderate O
and O
with O
reversible O
anemia O
developing O
in O
71 O
% O
of O
patients O
. O

Gastrointestinal O
side O
effects O
from O
CPDD O
were O
universal O
. O

HMM O
gastrointestinal O
toxicity O
necessitated O
discontinuation O
of O
the O
drug O
in O
5 O
patients O
. O

Severe O
nephrotoxicity O
was O
observed O
in O
2 O
patients O
but O
was O
reversible O
. O

There O
were O
no O
drug O
- O
related O
deaths O
. O

Nontraumatic O
dissecting O
aneurysm O
of O
the O
basilar O
artery O
. O

A O
case O
of O
nontraumatic O
dissecting O
aneurysm O
of O
the O
basilar O
artery O
in O
association O
with O
hypertension O
, O
smoke O
, O
and O
oral B
contraceptives I
is O
reported O
in O
a O
young O
female O
patient O
with O
a O
locked O
- O
in O
syndrome O
. O

A O
method O
for O
the O
measurement O
of O
tremor O
, O
and O
a O
comparison O
of O
the O
effects O
of O
tocolytic O
beta O
- O
mimetics O
. O

A O
method O
permitting O
measurement O
of O
finger O
tremor O
as O
a O
displacement O
- O
time O
curve O
is O
described O
, O
using O
a O
test O
system O
with O
simple O
amplitude O
calibration O
. O

The O
coordinates O
of O
the O
inversion O
points O
of O
the O
displacement O
- O
time O
curves O
were O
transferred O
through O
graphical O
input O
equipment O
to O
punched O
tape O
. O

By O
means O
of O
a O
computer O
program O
, O
periods O
and O
amplitudes O
of O
tremor O
oscillations O
were O
calculated O
and O
classified O
. O

The O
event O
frequency O
for O
each O
class O
of O
periods O
and O
amplitudes O
was O
determined O
. O

The O
actions O
of O
fenoterol B
- I
hydrobromide I
, O
ritodrin B
- I
HCl I
and O
placebo O
given O
to O
10 O
healthy O
subjects O
by O
intravenous O
infusion O
in O
a O
double O
- O
blind O
crossover O
study O
were O
tested O
by O
this O
method O
. O

At O
therapeutic O
doses O
both O
substances O
raised O
the O
mean O
tremor O
amplitude O
to O
about O
three O
times O
the O
control O
level O
. O

At O
the O
same O
time O
, O
the O
mean O
period O
within O
each O
class O
of O
amplitudes O
shortened O
by O
10 O
- O
- O
20 O
ms O
, O
whereas O
the O
mean O
periods O
calculated O
from O
all O
oscillations O
together O
did O
not O
change O
significantly O
. O

After O
the O
end O
of O
fenoterol B
- I
hydrobromide I
infusion O
, O
tremor O
amplitudes O
decreased O
significantly O
faster O
than O
those O
following O
ritodrin B
- I
HCl I
infusion O
. O

Propylthiouracil B
- O
induced O
hepatic O
damage O
. O

Two O
cases O
of O
propylthiouracil B
- O
induced O
liver O
damage O
have O
been O
observed O
. O

The O
first O
case O
is O
of O
an O
acute O
type O
of O
damage O
, O
proven O
by O
rechallenge O
; O
the O
second O
presents O
a O
clinical O
and O
histologic O
picture O
resembling O
chronic O
active O
hepatitis O
, O
with O
spontaneous O
remission O
. O

Studies O
on O
the O
bradycardia O
induced O
by O
bepridil B
. O

Bepridil B
, O
a O
novel O
active O
compound O
for O
prophylactic O
treatment O
of O
anginal O
attacks O
, O
induced O
persistent O
bradycardia O
and O
a O
non O
- O
specific O
anti O
- O
tachycardial O
effect O
, O
the O
mechanisms O
of O
which O
were O
investigated O
in O
vitro O
and O
in O
vivo O
. O

In O
vitro O
perfusion O
of O
bepridil B
in O
the O
life O
- O
support O
medium O
for O
isolated O
sino O
- O
atrial O
tissue O
from O
rabbit O
heart O
, O
caused O
a O
reduction O
in O
action O
potential O
( O
AP O
) O
spike O
frequency O
( O
recorded O
by O
KCl B
microelectrodes O
) O
starting O
at O
doses O
of O
5 O
X O
10 O
( O
- O
6 O
) O
M O
. O

This O
effect O
was O
dose O
- O
dependent O
up O
to O
concentrations O
of O
5 O
X O
10 O
( O
- O
5 O
) O
M O
, O
whereupon O
blockade O
of O
sinus O
activity O
set O
in O
. O

Bepridil B
at O
a O
dose O
of O
5 O
X O
10 O
( O
- O
6 O
) O
M O
, O
induced O
a O
concomitant O
reduction O
in O
AP O
amplitude O
( O
falling O
from O
71 O
+ O
/ O
- O
8 O
mV O
to O
47 O
+ O
/ O
- O
6 O
mV O
) O
, O
maximum O
systolic O
depolarization O
velocity O
( O
phase O
0 O
) O
which O
fell O
from O
1 O
. O
85 O
+ O
/ O
- O
0 O
. O
35 O
V O
/ O
s O
to O
0 O
. O
84 O
+ O
/ O
- O
0 O
. O
28 O
V O
/ O
s O
, O
together O
with O
maximum O
diastolic O
depolarization O
velocity O
( O
phase O
4 O
) O
which O
fell O
from O
38 O
+ O
/ O
- O
3 O
mV O
/ O
s O
to O
24 O
+ O
/ O
- O
5 O
mV O
/ O

s O
. O

In O
vivo O
injection O
of O
bepridil B
at O
a O
dose O
of O
5 O
mg O
/ O
kg O
( O
i O
. O
v O
. O
) O
into O
6 O
anaesthetized O
dogs O
which O
had O
undergone O
ablation O
of O
all O
the O
extrinsic O
cardiac O
afferent O
nerve O
supply O
, O
together O
with O
a O
bilateral O
medullo O
- O
adrenalectomy O
, O
caused O
a O
marked O
reduction O
in O
heart O
rate O
which O
fell O
from O
98 O
. O
7 O
+ O
/ O
- O
4 O
. O
2 O
beats O
/ O
min O
to O
76 O
+ O
/ O
- O
5 O
. O
3 O
beats O
/ O
min O
sustained O
for O
more O
than O
45 O
min O
. O

It O
is O
concluded O
that O
bepridil B
reduces O
heart O
rate O
by O
acting O
directly O
on O
the O
sinus O
node O
. O

This O
effect O
, O
which O
results O
in O
a O
flattening O
of O
the O
phase O
0 O
and O
phase O
4 O
slope O
, O
together O
with O
a O
longer O
AP O
duration O
, O
may O
be O
due O
to O
an O
increase O
in O
the O
time O
constants O
of O
slow O
inward O
ionic O
currents O
( O
already O
demonstrated O
elsewhere O
) O
, O
but O
also O
to O
an O
increased O
time O
constant O
for O
deactivation O
of O
the O
outward O
potassium B
current O
( O
Ip O
) O
. O

Hepatitis O
and O
renal O
tubular O
acidosis O
after O
anesthesia O
with O
methoxyflurane B
. O

A O
69 O
- O
year O
- O
old O
man O
operated O
for O
acute O
cholecystitis O
under O
methoxyflurane B
anesthesia O
developed O
postoperatively O
a O
hepatic O
insufficiency O
syndrome O
and O
renal O
tubular O
acidosis O
. O

Massive O
bleeding O
appeared O
during O
surgery O
which O
lasted O
for O
six O
hours O
. O

Postoperative O
evolution O
under O
supportive O
therapy O
was O
favourable O
. O

Complete O
recovery O
was O
confirmed O
by O
repeated O
controls O
performed O
over O
a O
period O
of O
one O
year O
after O
surgery O
. O

Pituitary O
response O
to O
luteinizing O
hormone O
- O
releasing O
hormone O
during O
haloperidol B
- O
induced O
hyperprolactinemia O
. O

The O
effects O
of O
a O
6 O
- O
hour O
infusion O
with O
haloperidol B
on O
serum O
prolactin O
and O
luteinizing O
hormone O
( O
LH O
) O
levels O
was O
studied O
in O
a O
group O
of O
male O
subjects O
. O

Five O
hours O
after O
starting O
the O
infusions O
, O
a O
study O
of O
the O
pituitary O
responses O
to O
LH O
- O
releasing O
hormone O
( O
LH O
- O
RH O
) O
was O
carried O
out O
. O

Control O
patients O
received O
infusions O
of O
0 O
. O
9 O
% O
NaCl B
solution O
. O

During O
the O
course O
of O
haloperidol B
infusions O
, O
significant O
hyperprolactinemia O
was O
found O
, O
together O
with O
an O
abolished O
pituitary O
response O
to O
LH O
- O
RH O
, O
as O
compared O
with O
responses O
of O
control O
subjects O
. O

Antirifampicin O
antibodies O
in O
acute O
rifampicin B
- O
associated O
renal O
failure O
. O

5 O
patients O
with O
acute O
renal O
failure O
( O
3 O
with O
thrombopenia O
and O
hemolysis O
) O
induced O
by O
the O
reintroduction O
of O
rifampicin B
are O
described O
. O

No O
correlation O
was O
found O
between O
the O
severity O
of O
clinical O
manifestations O
and O
the O
total O
dose O
taken O
by O
the O
patients O
. O

In O
all O
but O
1 O
patient O
, O
antirifampicin O
antibodies O
were O
detected O
. O

Antibodies O
suggested O
to O
be O
of O
the O
IgM O
class O
were O
detected O
in O
all O
3 O
patients O
with O
hematological O
disorders O
. O

The O
pattern O
of O
non O
- O
specific O
acute O
tubular O
necrosis O
found O
in O
the O
2 O
biopsied O
patients O
, O
indistinguishable O
from O
that O
of O
ischemic O
origin O
, O
raised O
the O
possibility O
of O
a O
vascular O
- O
mediated O
damage O
. O

In O
3 O
patients O
, O
the O
possibility O
of O
a O
triggering O
immunoallergic O
mechanism O
is O
discussed O
. O

Cardiovascular O
effects O
of O
hypotension O
induced O
by O
adenosine B
triphosphate I
and O
sodium B
nitroprusside I
on O
dogs O
with O
denervated O
hearts O
. O

Adenosine B
triphosphate I
( O
ATP B
) O
and O
sodium B
nitroprusside I
( O
SNP B
) O
are O
administered O
to O
patients O
to O
induce O
and O
control O
hypotension O
during O
anesthesia O
. O

SNP B
is O
authorized O
for O
clinical O
use O
in O
USA O
and O
UK O
, O
and O
ATP B
is O
clinically O
used O
in O
other O
countries O
such O
as O
Japan O
. O

We O
investigated O
how O
these O
two O
drugs O
act O
on O
the O
cardiovascular O
systems O
of O
20 O
dogs O
whose O
hearts O
had O
been O
denervated O
by O
a O
procedure O
we O
had O
devised O
. O

ATP B
( O
10 O
dogs O
) O
or O
SNP B
( O
10 O
dogs O
) O
was O
administered O
to O
reduce O
mean O
arterial O
pressure O
by O
30 O
% O
to O
70 O
% O
of O
control O
. O

Before O
, O
during O
and O
after O
induced O
hypotension O
, O
we O
measured O
major O
cardiovascular O
parameters O
. O

Hypotension O
induced O
by O
ATP B
was O
accompanied O
by O
significant O
decreases O
in O
mean O
pulmonary O
arterial O
pressure O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
central O
venous O
pressure O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
left O
ventricular O
end O
- O
diastolic O
pressure O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
total O
peripheral O
resistance O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
rate O
pressure O
product O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
total O
body O
oxygen B
consumption O
( O
p O
less O
than O
0 O
. O
05 O
) O
, O
and O
heart O
rate O
( O
p O
less O
than O
0 O
. O
001 O
) O
; O
all O
these O
variables O
returned O
normal O
within O
30 O
min O
after O
ATP B
was O

stopped O
. O

Cardiac O
output O
did O
not O
change O
. O

During O
hypotension O
produced O
by O
SNP B
similar O
decreases O
were O
observed O
in O
mean O
pulmonary O
arterial O
pressure O
( O
p O
less O
than O
0 O
. O
01 O
) O
, O
central O
venous O
pressure O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
left O
ventricular O
end O
- O
diastolic O
pressure O
( O
p O
less O
than O
0 O
. O
01 O
) O
, O
total O
peripheral O
resistance O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
rate O
pressure O
product O
( O
p O
less O
than O
0 O
. O
001 O
) O
, O
and O
oxygen B
content O
difference O
between O
arterial O
and O
mixed O
venous O
blood O
( O
p O
less O
than O
0 O
. O
05 O
) O
, O
while O
heart O
rate O
( O
p O
less O
than O
0 O
. O
001 O
) O
and O
cardiac O
output O
( O
p O

less O
than O
0 O
. O
05 O
) O
were O
increased O
. O

Recoveries O
of O
heart O
rate O
and O
left O
ventricular O
end O
- O
diastolic O
pressure O
were O
not O
shown O
within O
60 O
min O
after O
SNP B
had O
been O
stopped O
. O

Both O
ATP B
and O
SNP B
should O
act O
on O
the O
pacemaker O
tissue O
of O
the O
heart O
. O

Comparative O
study O
: O
Endografine B
( O
diatrizoate B
) O
, O
Vasurix B
polyvidone I
( O
acetrizoate B
) O
, O
Dimer B
- I
X I
( O
iocarmate B
) O
and O
Hexabrix B
( O
ioxaglate B
) O
in O
hysterosalpingography O
. O

Side O
effects O
of O
hysterosalpingography O
with O
Dimer B
- I
X I
, O
Hexabrix B
, O
Vasurix B
polyvidone I
and O
Endografine B
in O
142 O
consecutive O
patients O
, O
receiving O
one O
of O
the O
four O
tested O
media O
were O
evaluated O
from O
replies O
to O
postal O
questionnaires O
. O

The O
Dimer B
- I
X I
group O
had O
a O
higher O
incidence O
of O
nausea O
and O
dizziness O
. O

The O
Endografine B
group O
had O
a O
higher O
incidence O
of O
abdominal O
pain O
. O

These O
differences O
occur O
especially O
in O
the O
age O
groups O
under O
30 O
years O
. O

Hexabrix B
and O
Vasurix B
polyvidone I
are O
considered O
the O
best O
contrast O
media O
for O
hysterosalpingography O
and O
perhaps O
because O
of O
its O
low O
toxicity O
Hexabrix B
should O
be O
preferred O
. O

Post O
- O
suxamethonium B
pains O
in O
Nigerian O
surgical O
patients O
. O

Contrary O
to O
an O
earlier O
report O
by O
Coxon O
, O
scoline O
pain O
occurs O
in O
African O
negroes O
. O

Its O
incidence O
was O
determined O
in O
a O
prospective O
study O
involving O
a O
total O
of O
100 O
Nigerian O
patients O
( O
50 O
out O
- O
patients O
and O
50 O
in O
- O
patients O
) O
. O

About O
62 O
% O
of O
the O
out O
- O
patients O
developed O
scoline O
pain O
as O
compared O
with O
about O
26 O
% O
among O
the O
in O
- O
patients O
. O

The O
abolition O
of O
muscle O
fasciculations O
( O
by O
0 O
. O
075mg O
/ O
kg O
dose O
of O
Fazadinium B
) O
did O
not O
influence O
the O
occurrence O
of O
scoline O
pain O
. O

Neither O
the O
type O
of O
induction O
agent O
( O
Althesin B
or O
Thiopentone B
) O
nor O
the O
salt O
preparation O
of O
suxamethonium B
used O
( O
chloride B
or O
bromide B
) O
, O
affected O
the O
incidence O
of O
scoline O
pain O
. O

Invasive O
carcinoma O
of O
the O
renal O
pelvis O
following O
cyclophosphamide B
therapy O
for O
nonmalignant O
disease O
. O

A O
47 O
- O
year O
- O
old O
woman O
with O
right O
hydroureteronephrosis O
due O
to O
ureterovesical O
junction O
obstruction O
had O
gross O
hematuria O
after O
being O
treated O
for O
five O
years O
wtih O
cyclophosphamide B
for O
cerebral O
vasculitis O
. O

A O
right O
nephroureterectomy O
was O
required O
for O
control O
of O
bleeding O
. O

The O
pathology O
specimen O
contained O
clinically O
occult O
invasive O
carcinoma O
of O
the O
renal O
pelvis O
. O

Although O
the O
ability O
of O
cyclophosphamide B
to O
cause O
hemorrhagic O
cystitis O
and O
urine O
cytologic O
abnormalities O
indistinguishable O
from O
high O
grade O
carcinoma O
is O
well O
known O
, O
it O
is O
less O
widely O
appreciated O
that O
it O
is O
also O
associated O
with O
carcinoma O
of O
the O
urinary O
tract O
. O

Twenty O
carcinomas O
of O
the O
urinary O
bladder O
and O
one O
carcinoma O
of O
the O
prostate O
have O
been O
reported O
in O
association O
with O
its O
use O
. O

The O
present O
case O
is O
the O
first O
carcinoma O
of O
the O
renal O
pelvis O
reported O
in O
association O
with O
cyclophosphamide B
treatment O
. O

It O
is O
the O
third O
urinary O
tract O
cancer O
reported O
in O
association O
with O
cyclophosphamide B
treatment O
for O
nonmalignant O
disease O
. O

The O
association O
of O
the O
tumor O
with O
preexisting O
hydroureteronephrosis O
suggests O
that O
stasis O
prolonged O
and O
intensified O
exposure O
of O
upper O
urinary O
tract O
epithelium O
to O
cyclophosphamide B
. O

Patients O
who O
are O
candidates O
for O
long O
- O
term O
cyclophosphamide B
treatment O
should O
be O
routinely O
evaluated O
for O
obstructive O
uropathy O
. O

Medial O
changes O
in O
arterial O
spasm O
induced O
by O
L B
- I
norepinephrine I
. O

In O
normal O
rats O
, O
the O
media O
of O
small O
arteries O
( O
0 O
. O
4 O
- O
- O
0 O
. O
2 O
mm O
in O
diameter O
) O
previously O
was O
shown O
to O
contain O
intracellular O
vacuoles O
, O
identified O
ultrastructurally O
as O
herniations O
of O
one O
smooth O
muscle O
cell O
into O
another O
. O

The O
hypothesis O
that O
intense O
vasoconstriction O
would O
increase O
the O
number O
of O
such O
vacuoles O
has O
been O
tested O
. O

In O
the O
media O
of O
the O
saphenous O
artery O
and O
its O
distal O
branch O
, O
vasoconstriction O
induced O
by O
L B
- I
norepinephrine I
produced O
many O
cell O
- O
to O
- O
cell O
hernias O
within O
15 O
minutes O
. O

At O
1 O
day O
their O
number O
was O
reduced O
to O
about O
1 O
/ O
10 O
of O
the O
original O
number O
. O

By O
7 O
days O
the O
vessel O
was O
almost O
restored O
to O
normal O
. O

Triple O
stimulation O
over O
1 O
day O
induced O
more O
severe O
changes O
in O
the O
media O
. O

These O
findings O
suggest O
that O
smooth O
muscle O
cells O
are O
susceptible O
to O
damage O
in O
the O
course O
of O
their O
specific O
function O
. O

The O
experimental O
data O
are O
discussed O
in O
relation O
to O
medial O
changes O
observed O
in O
other O
instances O
of O
arterial O
spasm O
. O

Endothelial O
changes O
that O
developed O
in O
the O
same O
experimental O
model O
were O
described O
in O
a O
previous O
paper O
. O

Bilateral O
retinal O
artery O
and O
choriocapillaris O
occlusion O
following O
the O
injection O
of O
long O
- O
acting O
corticosteroid O
suspensions O
in O
combination O
with O
other O
drugs O
: O
I O
. O

Clinical O
studies O
. O

Two O
well O
- O
documented O
cases O
of O
bilateral O
retinal O
artery O
and O
choriocapillaris O
occlusions O
with O
blindness O
following O
head O
and O
neck O
soft O
- O
tissue O
injection O
with O
methylprednisolone B
acetate I
in O
combination O
with O
lidocaine B
, O
epinephrine B
, O
or O
penicillin B
are O
reported O
. O

One O
case O
had O
only O
a O
unilateral O
injection O
. O

The O
acute O
observations O
included O
hazy O
sensorium O
, O
superior O
gaze O
palsy O
, O
pupillary O
abnormalities O
, O
and O
conjunctival O
hemorrhages O
with O
edema O
. O

Follow O
- O
up O
changes O
showed O
marked O
visual O
loss O
, O
constricted O
visual O
fields O
, O
optic O
nerve O
pallor O
, O
vascular O
attenuation O
, O
and O
chorioretinal O
atrophy O
. O

The O
literature O
is O
reviewed O
, O
and O
possible O
causes O
are O
discussed O
. O

Abnormalities O
of O
the O
pupil O
and O
visual O
- O
evoked O
potential O
in O
quinine B
amblyopia O
. O

Total O
blindness O
with O
a O
transient O
tonic O
pupillary O
response O
, O
denervation O
supersensitivity O
, O
and O
abnormal O
visual O
- O
evoked O
potentials O
developed O
in O
a O
54 O
- O
year O
- O
old O
man O
after O
the O
use O
of O
quinine B
sulfate I
for O
leg O
cramps O
. O

He O
later O
recovered O
normal O
visual O
acuity O
. O

A O
transient O
tonic O
pupillary O
response O
, O
denervation O
supersensitivity O
, O
and O
abnormal O
visual O
- O
evoked O
potentials O
in O
quinine B
toxicity O
, O
to O
our O
knowledge O
, O
have O
not O
been O
previously O
reported O
. O

Suxamethonium B
- O
induced O
jaw O
stiffness O
and O
myalgia O
associated O
with O
atypical O
cholinesterase O
: O
case O
report O
. O

An O
11 O
- O
year O
- O
old O
boy O
was O
given O
halothane B
, O
nitrous B
oxide I
and O
oxygen B
, O
pancuronium B
0 O
. O
4 O
mg O
and O
suxamethonium B
100 O
mg O
for O
induction O
of O
anaesthesia O
. O

In O
response O
to O
this O
a O
marked O
jaw O
stiffness O
occurred O
which O
lasted O
for O
two O
minutes O
and O
the O
anaesthesia O
were O
terminated O
. O

Four O
hours O
of O
apnoea O
ensued O
and O
he O
suffered O
generalized O
severe O
myalgia O
lasting O
for O
one O
week O
. O

He O
was O
found O
to O
have O
atypical O
plasma O
cholinesterase O
with O
a O
dibucaine B
number O
of O
12 O
, O
indicating O
homozygocity O
. O

This O
was O
verified O
by O
study O
of O
the O
family O
. O

The O
case O
shows O
that O
prolonged O
jaw O
rigidity O
and O
myalgia O
may O
occur O
after O
suxamethonium B
in O
patients O
with O
atypical O
cholinesterase O
despite O
pretreatment O
with O
pancuronium B
. O

Indomethacin B
- O
induced O
hyperkalemia O
in O
three O
patients O
with O
gouty O
arthritis O
. O

We O
describe O
three O
patients O
in O
whom O
severe O
, O
life O
- O
threatening O
hyperkalemia O
and O
renal O
insufficiency O
developed O
after O
treatment O
of O
acute O
gouty O
arthritis O
with O
indomethacin B
. O

This O
complication O
may O
result O
from O
an O
inhibition O
of O
prostaglandin B
synthesis O
and O
consequent O
hyporeninemic O
hypoaidosteronism O
. O

Careful O
attention O
to O
renal O
function O
and O
potassium B
balance O
in O
patients O
receiving O
indomethacin B
or O
other O
nonsteroidal O
anti O
- O
inflammatory O
agents O
, O
particularly O
in O
those O
patients O
with O
diabetes O
mellitus O
or O
preexisting O
renal O
disease O
, O
will O
help O
prevent O
this O
potentially O
serious O
complication O
. O

Etomidate B
: O
a O
foreshortened O
clinical O
trial O
. O

A O
clinical O
evaluation O
of O
etomidate B
for O
outpatient O
cystoscopy O
was O
embarked O
upon O
. O

Unpremedicated O
patients O
were O
given O
fentanyl B
1 O
microgram O
/ O
kg O
followed O
by O
etomidate B
0 O
. O
3 O
mg O
/ O
kg O
. O

Anaesthesia O
was O
maintained O
with O
intermittent O
etomidate B
in O
2 O
- O
4 O
mg O
doses O
. O

Patients O
were O
interviewed O
personally O
later O
the O
same O
day O
, O
and O
by O
questionnaire O
three O
to O
four O
weeks O
later O
. O

The O
trial O
was O
discontinued O
after O
20 O
cases O
because O
of O
an O
unacceptable O
incidence O
of O
side O
effects O
. O

Venous O
pain O
occurred O
in O
68 O
% O
of O
patients O
and O
50 O
% O
had O
redness O
, O
pain O
or O
swelling O
related O
to O
the O
injection O
site O
, O
in O
some O
cases O
lasting O
up O
to O
three O
weeks O
after O
anaesthesia O
. O

Skeletal O
movements O
occurred O
in O
50 O
% O
of O
patients O
; O
30 O
% O
experienced O
respiratory O
upset O
, O
one O
sufficiently O
severe O
to O
necessitate O
abandoning O
the O
technique O
. O

Nausea O
and O
vomiting O
occurred O
in O
40 O
% O
and O
25 O
% O
had O
disturbing O
emergence O
psychoses O
. O

Levodopa B
- O
induced O
dyskinesias O
are O
improved O
by O
fluoxetine B
. O

We O
evaluated O
the O
severity O
of O
motor O
disability O
and O
dyskinesias O
in O
seven O
levodopa B
- O
responsive O
patients O
with O
Parkinson O
' O
s O
disease O
after O
an O
acute O
challenge O
with O
the O
mixed O
dopamine B
agonist O
, O
apomorphine B
, O
before O
and O
after O
the O
administration O
of O
fluoxetine B
( O
20 O
mg O
twice O
per O
day O
) O
for O
11 O
+ O
/ O
- O
1 O
days O
. O

After O
fluoxetine B
treatment O
, O
there O
was O
a O
significant O
47 O
% O
improvement O
( O
p O
< O
0 O
. O
05 O
) O
of O
apomorphine B
- O
induced O
dyskinesias O
without O
modification O
of O
parkinsonian O
motor O
disability O
. O

The O
dyskinesias O
were O
reduced O
predominantly O
in O
the O
lower O
limbs O
during O
the O
onset O
and O
disappearance O
of O
dystonic O
dyskinesias O
( O
onset O
- O
and O
end O
- O
of O
- O
dose O
dyskinesias O
) O
and O
in O
the O
upper O
limbs O
during O
choreic O
mid O
- O
dose O
dyskinesias O
. O

The O
results O
suggest O
that O
increased O
brain O
serotoninergic B
transmission O
with O
fluoxetine B
may O
reduce O
levodopa B
- O
or O
dopamine B
agonist O
- O
induced O
dyskinesias O
without O
aggravating O
parkinsonian O
motor O
disability O
. O

A O
large O
population O
- O
based O
follow O
- O
up O
study O
of O
trimethoprim B
- I
sulfamethoxazole I
, O
trimethoprim B
, O
and O
cephalexin B
for O
uncommon O
serious O
drug O
toxicity O
. O

We O
conducted O
a O
population O
- O
based O
45 O
- O
day O
follow O
- O
up O
study O
of O
232 O
, O
390 O
people O
who O
were O
prescribed O
trimethoprim B
- I
sulfamethoxazole I
( O
TMP B
- I
SMZ I
) O
, O
266 O
, O
951 O
prescribed O
trimethoprim B
alone O
, O
and O
196 O
, O
397 O
prescribed O
cephalexin B
, O
to O
estimate O
the O
risk O
of O
serious O
liver O
, O
blood O
, O
skin O
, O
and O
renal O
disorders O
resulting O
in O
referral O
or O
hospitalization O
associated O
with O
these O
drugs O
. O

The O
results O
were O
based O
on O
information O
recorded O
on O
office O
computers O
by O
selected O
general O
practitioners O
in O
the O
United O
Kingdom O
, O
together O
with O
a O
review O
of O
clinical O
records O
. O

The O
risk O
of O
clinically O
important O
idiopathic O
liver O
disease O
was O
similar O
for O
persons O
prescribed O
TMP B
- I
SMZ I
( O
5 O
. O
2 O
/ O
100 O
, O
000 O
) O
and O
those O
prescribed O
trimethoprim B
alone O
( O
3 O
. O
8 O
/ O
100 O
, O
000 O
) O
. O

The O
risk O
for O
those O
prescribed O
cephalexin B
was O
somewhat O
lower O
( O
2 O
. O
0 O
/ O
100 O
, O
000 O
) O
. O

Only O
five O
patients O
experienced O
blood O
disorders O
, O
one O
of O
whom O
was O
exposed O
to O
TMP B
- I
SMZ I
; O
of O
seven O
with O
erythema O
multiforme O
and O
Stevens O
- O
Johnson O
syndrome O
, O
four O
were O
exposed O
to O
TMP B
- I
SMZ I
. O

The O
one O
case O
of O
toxic O
epidermal O
necrolysis O
occurred O
in O
a O
patient O
who O
took O
cephalexin B
. O

Finally O
, O
only O
five O
cases O
of O
acute O
parenchymal O
renal O
disease O
occurred O
, O
none O
likely O
to O
be O
caused O
by O
a O
study O
drug O
. O

We O
conclude O
that O
the O
risk O
of O
the O
serious O
diseases O
studied O
is O
small O
for O
the O
three O
agents O
, O
and O
compares O
reasonably O
with O
the O
risk O
for O
many O
other O
antibiotics O
. O

Clinical O
safety O
of O
lidocaine B
in O
patients O
with O
cocaine B
- O
associated O
myocardial O
infarction O
. O

STUDY O
OBJECTIVE O
: O
To O
evaluate O
the O
safety O
of O
lidocaine B
in O
the O
setting O
of O
cocaine B
- O
induced O
myocardial O
infarction O
( O
MI O
) O
. O

DESIGN O
: O
A O
retrospective O
, O
multicenter O
study O
. O

SETTING O
: O
Twenty O
- O
nine O
university O
, O
university O
- O
affiliated O
, O
or O
community O
hospitals O
during O
a O
6 O
- O
year O
period O
( O
total O
of O
117 O
cumulative O
hospital O
- O
years O
) O
. O

PARTICIPANTS O
: O
Patients O
with O
cocaine B
- O
associated O
MI O
who O
received O
lidocaine B
in O
the O
emergency O
department O
. O

RESULTS O
: O
Of O
29 O
patients O
who O
received O
lidocaine B
in O
the O
setting O
of O
cocaine B
- O
associated O
MI O
, O
no O
patient O
died O
; O
exhibited O
bradydysrhythmias O
, O
ventricular O
tachycardia O
, O
or O
ventricular O
fibrillation O
; O
or O
experienced O
seizures O
after O
administration O
of O
lidocaine B
( O
95 O
% O
confidence O
interval O
, O
0 O
% O
to O
11 O
% O
) O
. O

CONCLUSION O
: O
Despite O
theoretical O
concerns O
that O
lidocaine B
may O
enhance O
cocaine B
toxicity O
, O
the O
use O
of O
lidocaine B
in O
patients O
with O
cocaine B
- O
associated O
MI O
was O
not O
associated O
with O
significant O
cardiovascular O
or O
central O
nervous O
system O
toxicity O
. O

Experimental O
progressive O
muscular O
dystrophy O
and O
its O
treatment O
with O
high O
doses O
anabolizing O
agents O
. O

We O
are O
still O
a O
long O
way O
from O
discovering O
an O
unequivocal O
pathogenetic O
interpretation O
of O
progressive O
muscular O
dystrophy O
in O
man O
. O

Noteworthy O
efforts O
have O
been O
made O
in O
the O
experimental O
field O
; O
a O
recessive O
autosomic O
form O
found O
in O
the O
mouse O
seems O
to O
bear O
the O
closest O
resemblance O
to O
the O
human O
form O
from O
the O
genetic O
point O
of O
view O
. O

Myopathy O
due O
to O
lack O
of O
vitamin B
E I
and O
myopathy O
induced O
by O
certain O
viruses O
have O
much O
in O
common O
anatomically O
and O
pathologically O
with O
the O
human O
form O
. O

The O
authors O
induced O
myodystrophy O
in O
the O
rat O
by O
giving O
it O
a O
diet O
lacking O
in O
vitamin B
E I
. O

The O
pharmacological O
characteristics O
of O
vitamin B
E I
and O
the O
degenerative O
changes O
brought O
about O
by O
its O
deficiency O
, O
especially O
in O
the O
muscles O
, O
are O
illustrated O
. O

It O
is O
thus O
confirmed O
that O
the O
histological O
characteristics O
of O
myopathic O
rat O
muscle O
induced O
experimentally O
are O
extraordinarily O
similar O
to O
those O
of O
human O
myopathy O
as O
confirmed O
during O
biopsies O
performed O
at O
the O
Orthopaedic O
Traumatological O
Centre O
, O
Florence O
. O

The O
encouraging O
results O
obtained O
in O
various O
authoratative O
departments O
in O
myopathic O
patients O
by O
using O
anabolizing O
steroids B
have O
encouraged O
the O
authors O
to O
investigate O
the O
beneficial O
effects O
of O
one O
anabolizing O
agent O
( O
Dianabol O
, O
CIBA O
) O
at O
high O
doses O
in O
rats O
rendered O
myopathic O
by O
a O
diet O
deficient O
in O
vitamin B
E I
. O

In O
this O
way O
they O
obtained O
appreciable O
changes O
in O
body O
weight O
( O
increased O
from O
50 O
to O
70 O
g O
after O
forty O
days O
at O
a O
dose O
of O
5 O
mg O
per O
day O
of O
anabolizing O
agent O
) O
, O
but O
most O
of O
all O
they O
found O
histological O
changes O
due O
to O
" O
regenerative O
" O
changes O
in O
the O
muscle O
tissue O
, O
which O
however O
maintained O
its O
myopathic O
characteristics O
in O
the O
control O
animals O
that O
were O
not O
treated O
with O
the O
anabolizing O
agent O
. O

The O
authors O
conclude O
by O
affirming O
the O
undoubted O
efficacy O
of O
the O
anabolizing O
steroids B
in O
experimental O
myopathic O
disease O
, O
but O
they O
have O
reservations O
as O
to O
the O
transfer O
of O
the O
results O
into O
the O
human O
field O
, O
where O
high O
dosage O
cannot O
be O
carried O
out O
continuously O
because O
of O
the O
effects O
of O
the O
drug O
on O
virility O
; O
because O
the O
tissue O
injury O
too O
often O
occurs O
at O
an O
irreversible O
stage O
vis O
- O
a O
- O
vis O
the O
" O
regeneration O
" O
of O
the O
muscle O
tissue O
; O
and O
finally O
because O
the O
dystrophic O
injurious O
agent O
is O
certainly O
not O
the O
lack O
of O
vitamin B
E I
but O
something O
as O
yet O
unknown O
. O

Paclitaxel B
3 O
- O
hour O
infusion O
given O
alone O
and O
combined O
with O
carboplatin B
: O
preliminary O
results O
of O
dose O
- O
escalation O
trials O
. O

Paclitaxel B
( O
Taxol B
; O
Bristol O
- O
Myers O
Squibb O
Company O
, O
Princeton O
, O
NJ O
) O
by O
3 O
- O
hour O
infusion O
was O
combined O
with O
carboplatin B
in O
a O
phase O
I O
/ O
II O
study O
directed O
to O
patients O
with O
non O
- O
small O
cell O
lung O
cancer O
. O

Carboplatin B
was O
given O
at O
a O
fixed O
target O
area O
under O
the O
concentration O
- O
time O
curve O
of O
6 O
. O
0 O
by O
the O
Calvert O
formula O
, O
whereas O
paclitaxel B
was O
escalated O
in O
patient O
cohorts O
from O
150 O
mg O
/ O
m2 O
( O
dose O
level O
I O
) O
to O
175 O
, O
200 O
, O
225 O
, O
and O
250 O
mg O
/ O
m2 O
. O

The O
225 O
mg O
/ O
m2 O
level O
was O
expanded O
for O
the O
phase O
II O
study O
since O
the O
highest O
level O
achieved O
( O
250 O
mg O
/ O
m2 O
) O
required O
modification O
because O
of O
nonhematologic O
toxicities O
( O
arthralgia O
and O
sensory O
neuropathy O
) O
. O

Therapeutic O
effects O
were O
noted O
at O
all O
dose O
levels O
, O
with O
objective O
responses O
in O
17 O
( O
two O
complete O
and O
15 O
partial O
regressions O
) O
of O
41 O
previously O
untreated O
patients O
. O

Toxicities O
were O
compared O
with O
a O
cohort O
of O
patients O
in O
a O
phase O
I O
trial O
of O
paclitaxel B
alone O
at O
identical O
dose O
levels O
. O

Carboplatin B
did O
not O
appear O
to O
add O
to O
the O
hematologic O
toxicities O
observed O
, O
and O
the O
paclitaxel B
/ O
carboplatin B
combination O
could O
be O
dosed O
every O
3 O
weeks O
. O

The O
dose O
- O
dependent O
effect O
of O
misoprostol B
on O
indomethacin B
- O
induced O
renal O
dysfunction O
in O
well O
compensated O
cirrhosis O
. O

Misoprostol B
( O
200 O
micrograms O
) O
has O
been O
shown O
to O
acutely O
counteract O
the O
indomethacin B
- O
induced O
renal O
dysfunction O
in O
well O
compensated O
cirrhotic O
patients O
. O

The O
aim O
of O
this O
study O
was O
to O
determine O
if O
the O
prophylactic O
value O
of O
misoprostol B
was O
dose O
- O
dependent O
. O

Parameters O
of O
renal O
hemodynamics O
and O
tubular O
sodium B
and O
water O
handling O
were O
assessed O
by O
clearance O
techniques O
in O
26 O
well O
compensated O
cirrhotic O
patients O
before O
and O
after O
an O
oral O
combination O
of O
50 O
mg O
of O
indomethacin B
and O
various O
doses O
of O
misoprostol B
. O

The O
200 O
- O
micrograms O
dose O
was O
able O
to O
totally O
abolish O
the O
deleterious O
renal O
effects O
of O
indomethacin B
, O
whereas O
the O
800 O
- O
micrograms O
dose O
resulted O
in O
significant O
worsening O
of O
renal O
hemodynamics O
and O
sodium B
retention O
. O

These O
changes O
were O
maximal O
in O
the O
hour O
immediately O
after O
medications O
and O
slowly O
returned O
toward O
base O
- O
line O
levels O
thereafter O
. O

These O
results O
suggest O
that O
the O
renal O
protective O
effects O
of O
misoprostol B
is O
dose O
- O
dependent O
. O

However O
, O
until O
this O
apparent O
ability O
of O
200 O
micrograms O
of O
misoprostol B
to O
prevent O
the O
adverse O
effects O
of O
indomethacin B
on O
renal O
function O
is O
confirmed O
with O
chronic O
frequent O
dosing O
, O
it O
would O
be O
prudent O
to O
avoid O
nonsteroidal O
anti O
- O
inflammatory O
therapy O
in O
patients O
with O
cirrhosis O
. O

Increased O
frequency O
and O
severity O
of O
angio O
- O
oedema O
related O
to O
long O
- O
term O
therapy O
with O
angiotensin B
- O
converting O
enzyme O
inhibitor O
in O
two O
patients O
. O

Adverse O
reactions O
to O
drugs O
are O
well O
recognized O
as O
a O
cause O
of O
acute O
or O
chronic O
urticaria O
, O
and O
angio O
- O
oedema O
. O

Angiotensin B
- O
converting I
enzyme I
( I
ACE I
) I
inhibitors I
, O
used O
to O
treat O
hypertension O
and O
congestive O
heart O
failure O
, O
were O
introduced O
in O
Europe O
in O
the O
middle O
of O
the O
eighties O
, O
and O
the O
use O
of O
these O
drugs O
has O
increased O
progressively O
. O

Soon O
after O
the O
introduction O
of O
ACE B
inhibitors I
, O
acute O
bouts O
of O
angio O
- O
oedema O
were O
reported O
in O
association O
with O
the O
use O
of O
these O
drugs O
. O

We O
wish O
to O
draw O
attention O
to O
the O
possibility O
of O
adverse O
reactions O
to O
ACE B
inhibitors I
after O
long O
- O
term O
use O
and O
in O
patients O
with O
pre O
- O
existing O
angio O
- O
oedema O
. O

Myoclonus O
associated O
with O
lorazepam B
therapy O
in O
very O
- O
low O
- O
birth O
- O
weight O
infants O
. O

Lorazepam B
is O
being O
used O
with O
increasing O
frequency O
as O
a O
sedative O
in O
the O
newborn O
and O
the O
young O
infant O
. O

Concern O
has O
been O
raised O
with O
regard O
to O
the O
safety O
of O
lorazepam B
in O
this O
age O
group O
, O
especially O
in O
very O
- O
low O
- O
birth O
- O
weight O
( O
VLBW O
; O
< O
1 O
, O
500 O
g O
) O
infants O
. O

Three O
young O
infants O
, O
all O
of O
birth O
weight O
< O
1 O
, O
500 O
g O
, O
experienced O
myoclonus O
following O
the O
intravenous O
administration O
of O
lorazepam B
. O

The O
potential O
neurotoxic O
effects O
of O
the O
drug O
( O
and O
its O
vehicle O
) O
in O
this O
population O
are O
discussed O
. O

Injectable O
lorazepam B
should O
be O
used O
with O
caution O
in O
VLBW O
infants O
. O

Transvenous O
right O
ventricular O
pacing O
during O
cardiopulmonary O
resuscitation O
of O
pediatric O
patients O
with O
acute O
cardiomyopathy O
. O

We O
describe O
the O
cardiopulmonary O
resuscitation O
efforts O
on O
five O
patients O
who O
presented O
in O
acute O
circulatory O
failure O
from O
myocardial O
dysfunction O
. O

Three O
patients O
had O
acute O
viral O
myocarditis O
, O
one O
had O
a O
carbamazepine B
- O
induced O
acute O
eosinophilic O
myocarditis O
, O
and O
one O
had O
cardiac O
hemosiderosis O
resulting O
in O
acute O
cardiogenic O
shock O
. O

All O
patients O
were O
continuously O
monitored O
with O
central O
venous O
and O
arterial O
catheters O
in O
addition O
to O
routine O
noninvasive O
monitoring O
. O

An O
introducer O
sheath O
, O
a O
pacemaker O
, O
and O
sterile O
pacing O
wires O
were O
made O
readily O
available O
for O
the O
patients O
, O
should O
the O
need O
arise O
to O
terminate O
resistant O
cardiac O
dysrhythmias O
. O

All O
patients O
developed O
cardiocirculatory O
arrest O
associated O
with O
extreme O
hypotension O
and O
dysrhythmias O
within O
the O
first O
48 O
hours O
of O
their O
admission O
to O
the O
pediatric O
intensive O
care O
unit O
( O
PICU O
) O
. O

Right O
ventricular O
pacemaker O
wires O
were O
inserted O
in O
all O
of O
them O
during O
cardiopulmonary O
resuscitation O
( O
CPR O
) O
. O

In O
four O
patients O
, O
cardiac O
pacing O
was O
used O
, O
resulting O
in O
a O
temporary O
captured O
rhythm O
and O
restoration O
of O
their O
cardiac O
output O
. O

These O
patients O
had O
a O
second O
event O
of O
cardiac O
arrest O
, O
resulting O
in O
death O
, O
within O
10 O
to O
60 O
minutes O
. O

In O
one O
patient O
, O
cardiac O
pacing O
was O
not O
used O
, O
because O
he O
converted O
to O
normal O
sinus O
rhythm O
by O
electrical O
defibrillation O
within O
three O
minutes O
of O
initiating O
CPR O
. O

We O
conclude O
that O
cardiac O
pacing O
during O
resuscitative O
efforts O
in O
pediatric O
patients O
suffering O
from O
acute O
myocardial O
dysfunction O
may O
not O
have O
long O
- O
term O
value O
in O
and O
of O
itself O
; O
however O
, O
if O
temporary O
hemodynamic O
stability O
is O
achieved O
by O
this O
procedure O
, O
it O
may O
provide O
additional O
time O
needed O
to O
institute O
other O
therapeutic O
modalities O
. O

Efficacy O
and O
safety O
of O
granisetron B
, O
a O
selective O
5 B
- I
hydroxytryptamine I
- O
3 O
receptor O
antagonist O
, O
in O
the O
prevention O
of O
nausea O
and O
vomiting O
induced O
by O
high O
- O
dose O
cisplatin B
. O

PURPOSE O
: O
To O
assess O
the O
antiemetic O
effects O
and O
safety O
profile O
of O
four O
different O
doses O
of O
granisetron B
( O
Kytril B
; O
SmithKline O
Beecham O
Pharmaceuticals O
, O
Philadelphia O
, O
PA O
) O
when O
administered O
as O
a O
single O
intravenous O
( O
IV O
) O
dose O
for O
prophylaxis O
of O
cisplatin B
- O
induced O
nausea O
and O
vomiting O
. O

PATIENTS O
AND O
METHODS O
: O
One O
hundred O
eighty O
- O
four O
chemotherapy O
- O
naive O
patients O
receiving O
high O
- O
dose O
cisplatin B
( O
81 O
to O
120 O
mg O
/ O
m2 O
) O
were O
randomized O
to O
receive O
one O
of O
four O
granisetron B
doses O
( O
5 O
, O
10 O
, O
20 O
, O
or O
40 O
micrograms O
/ O
kg O
) O
administered O
before O
chemotherapy O
. O

Patients O
were O
observed O
on O
an O
inpatient O
basis O
for O
18 O
to O
24 O
hours O
, O
and O
vital O
signs O
, O
nausea O
, O
vomiting O
, O
retching O
, O
and O
appetite O
were O
assessed O
. O

Safety O
analyses O
included O
incidence O
of O
adverse O
experiences O
and O
laboratory O
parameter O
changes O
. O

RESULTS O
: O
After O
granisetron B
doses O
of O
5 O
, O
10 O
, O
20 O
, O
and O
40 O
micrograms O
/ O
kg O
, O
a O
major O
response O
( O
< O
or O
= O
two O
vomiting O
or O
retching O
episodes O
, O
and O
no O
antiemetic O
rescue O
) O
was O
recorded O
in O
23 O
% O
, O
57 O
% O
, O
58 O
% O
, O
and O
60 O
% O
of O
patients O
, O
respectively O
, O
and O
a O
complete O
response O
( O
no O
vomiting O
or O
retching O
, O
and O
no O
antiemetic O
rescue O
) O
in O
18 O
% O
, O
41 O
% O
, O
40 O
% O
, O
and O
47 O
% O
of O
patients O
, O
respectively O
. O

There O
was O
a O
statistically O
longer O
time O
to O
first O
episode O
of O
nausea O
( O
P O
= O
. O
0015 O
) O
and O
vomiting O
( O
P O
= O
. O
0001 O
) O
, O
and O
fewer O
patients O
were O
administered O
additional O
antiemetic O
medication O
in O
the O
10 O
- O
micrograms O
/ O
kg O
dosing O
groups O
than O
in O
the O
5 O
- O
micrograms O
/ O
kg O
dosing O
group O
. O

As O
granisetron B
dose O
increased O
, O
appetite O
return O
increased O
( O
P O
= O
. O
040 O
) O
. O

Headache O
was O
the O
most O
frequently O
reported O
adverse O
event O
( O
20 O
% O
) O
. O

CONCLUSION O
: O
A O
single O
10 O
- O
, O
20 O
- O
, O
or O
40 O
- O
micrograms O
/ O
kg O
dose O
of O
granisetron B
was O
effective O
in O
controlling O
vomiting O
in O
57 O
% O
to O
60 O
% O
of O
patients O
who O
received O
cisplatin B
at O
doses O
greater O
than O
81 O
mg O
/ O
m2 O
and O
totally O
prevented O
vomiting O
in O
40 O
% O
to O
47 O
% O
of O
patients O
. O

There O
were O
no O
statistically O
significant O
differences O
in O
efficacy O
between O
the O
10 O
- O
micrograms O
/ O
kg O
dose O
and O
the O
20 O
- O
and O
40 O
- O
micrograms O
/ O
kg O
doses O
. O

Granisetron B
was O
well O
tolerated O
at O
all O
doses O
. O

Adverse O
interaction O
between O
clonidine B
and O
verapamil B
. O

OBJECTIVE O
: O
To O
report O
two O
cases O
of O
a O
possible O
adverse O
interaction O
between O
clonidine B
and O
verapamil B
resulting O
in O
atrioventricular O
( O
AV O
) O
block O
in O
both O
patients O
and O
severe O
hypotension O
in O
one O
patient O
. O

CASE O
SUMMARIES O
: O
A O
54 O
- O
year O
- O
old O
woman O
with O
hyperaldosteronism O
was O
treated O
with O
verapamil B
480 O
mg O
/ O
d O
and O
spironolactone B
100 O
mg O
/ O
d O
. O

After O
the O
addition O
of O
a O
minimal O
dose O
of O
clonidine B
( O
0 O
. O
15 O
mg O
bid O
) O
, O
she O
developed O
complete O
AV O
block O
and O
severe O
hypotension O
, O
which O
resolved O
upon O
cessation O
of O
all O
medications O
. O

A O
65 O
- O
year O
- O
old O
woman O
was O
treated O
with O
extended O
- O
release O
verapamil B
240 O
mg O
/ O
d O
. O

After O
the O
addition O
of O
clonidine B
0 O
. O
15 O
mg O
bid O
she O
developed O
complete O
AV O
block O
, O
which O
resolved O
after O
all O
therapy O
was O
stopped O
. O

DISCUSSION O
: O
An O
adverse O
interaction O
between O
clonidine B
and O
verapamil B
has O
not O
been O
reported O
previously O
. O

We O
describe O
two O
such O
cases O
and O
discuss O
the O
various O
mechanisms O
that O
might O
cause O
such O
an O
interaction O
. O

Clinicians O
should O
be O
acquainted O
with O
this O
possibly O
fatal O
interaction O
between O
two O
commonly O
used O
antihypertensive O
drugs O
. O

CONCLUSIONS O
: O
Caution O
is O
recommended O
in O
combining O
clonidine B
and O
verapamil B
therapy O
, O
even O
in O
patients O
who O
do O
not O
have O
sinus O
or O
AV O
node O
dysfunction O
. O

The O
two O
drugs O
may O
act O
synergistically O
on O
both O
the O
AV O
node O
and O
the O
peripheral O
circulation O
. O

Pharmacological O
studies O
on O
a O
new O
dihydrothienopyridine B
calcium B
antagonist O
, O
S B
- I
312 I
- I
d I
. O

5th O
communication O
: O
anticonvulsant O
effects O
in O
mice O
. O

S B
- I
312 I
, O
S B
- I
312 I
- I
d I
, O
but O
not O
S B
- I
312 I
- I
l I
, O
L O
- O
type O
calcium B
channel O
antagonists O
, O
showed O
anticonvulsant O
effects O
on O
the O
audiogenic O
tonic O
convulsions O
in O
DBA O
/ O
2 O
mice O
; O
and O
their O
ED50 O
values O
were O
18 O
. O
4 O
( O
12 O
. O
8 O
- O
27 O
. O
1 O
) O
mg O
/ O
kg O
, O
p O
. O
o O
. O
and O
15 O
. O
0 O
( O
10 O
. O
2 O
- O
23 O
. O
7 O
) O
mg O
/ O
kg O
, O
p O
. O
o O
. O
, O
respectively O
, O
while O
that O
of O
flunarizine B
was O
34 O
. O
0 O
( O
26 O
. O
0 O
- O
44 O
. O
8 O
) O
mg O
/ O
kg O
, O
p O

. O
o O
. O

Although O
moderate O
anticonvulsant O
effects O
of O
S B
- I
312 I
- I
d I
in O
higher O
doses O
were O
observed O
against O
the O
clonic O
convulsions O
induced O
by O
pentylenetetrazole B
( O
85 O
mg O
/ O
kg O
, O
s O
. O
c O
. O
) O
or O
bemegride B
( O
40 O
mg O
/ O
kg O
, O
s O
. O
c O
. O
) O
, O
no O
effects O
were O
observed O
in O
convulsions O
induced O
by O
N B
- I
methyl I
- I
D I
- I
aspartate I
, O
picrotoxin B
, O
or O
electroshock O
in O
Slc O
: O
ddY O
mice O
. O

S B
- I
312 I
- I
d I
may O
be O
useful O
in O
the O
therapy O
of O
certain O
types O
of O
human O
epilepsy O
. O

Transmural O
myocardial O
infarction O
with O
sumatriptan B
. O

For O
sumatriptan B
, O
tightness O
in O
the O
chest O
caused O
by O
an O
unknown O
mechanism O
has O
been O
reported O
in O
3 O
- O
5 O
% O
of O
users O
. O

We O
describe O
a O
47 O
- O
year O
- O
old O
woman O
with O
an O
acute O
myocardial O
infarction O
after O
administration O
of O
sumatriptan B
6 O
mg O
subcutaneously O
for O
cluster O
headache O
. O

The O
patient O
had O
no O
history O
of O
underlying O
ischaemic O
heart O
disease O
or O
Prinzmetal O
' O
s O
angina O
. O

She O
recovered O
without O
complications O
. O

Flumazenil B
induces O
seizures O
and O
death O
in O
mixed O
cocaine B
- O
diazepam B
intoxications O
. O

STUDY O
HYPOTHESIS O
: O
Administration O
of O
the O
benzodiazepine B
antagonist O
flumazenil B
may O
unmask O
seizures O
in O
mixed O
cocaine B
- O
benzodiazepine B
intoxication O
. O

DESIGN O
: O
Male O
Sprague O
- O
Dawley O
rats O
received O
100 O
mg O
/ O
kg O
cocaine B
IP O
alone O
, O
5 O
mg O
/ O
kg O
diazepam B
alone O
, O
or O
a O
combination O
of O
diazepam B
and O
cocaine B
. O

Three O
minutes O
later O
, O
groups O
were O
challenged O
with O
vehicle O
or O
flumazenil B
5 O
or O
10 O
mg O
/ O
kg O
IP O
. O

Animal O
behavior O
, O
seizures O
( O
time O
to O
and O
incidence O
) O
, O
death O
( O
time O
to O
and O
incidence O
) O
, O
and O
cortical O
EEG O
tracings O
were O
recorded O
. O

INTERVENTIONS O
: O
Administration O
of O
flumazenil B
to O
animals O
after O
they O
had O
received O
a O
combination O
dose O
of O
cocaine B
and O
diazepam B
. O

RESULTS O
: O
In O
group O
1 O
, O
animals O
received O
cocaine B
followed O
by O
vehicle O
. O

This O
resulted O
in O
100 O
% O
developing O
seizures O
and O
death O
. O

Group O
2 O
received O
diazepam B
alone O
followed O
by O
vehicle O
. O

Animals O
became O
somnolent O
and O
none O
died O
. O

Group O
3 O
received O
diazepam B
followed O
by O
5 O
mg O
/ O
kg O
flumazenil B
. O

Animals O
became O
somnolent O
after O
diazepam B
and O
then O
active O
after O
flumazenil B
administration O
. O

In O
group O
4 O
, O
a O
combination O
of O
cocaine B
and O
diazepam B
was O
administered O
simultaneously O
. O

This O
resulted O
in O
no O
overt O
or O
EEG O
- O
detectable O
seizures O
and O
a O
50 O
% O
incidence O
of O
death O
. O

Group O
5 O
received O
a O
similar O
combination O
of O
cocaine B
and O
diazepam B
, O
followed O
later O
by O
5 O
mg O
/ O
kg O
flumazenil B
. O

This O
resulted O
in O
an O
increased O
incidence O
of O
seizures O
, O
90 O
% O
( O
P O
< O
. O
01 O
) O
, O
and O
death O
, O
100 O
% O
( O
P O
< O
or O
= O
. O
01 O
) O
, O
compared O
with O
group O
4 O
. O

Group O
6 O
received O
cocaine B
and O
diazepam B
followed O
by O
10 O
mg O
/ O
kg O
flumazenil B
. O

This O
also O
resulted O
in O
an O
increased O
incidence O
of O
seizures O
, O
90 O
% O
( O
P O
< O
or O
= O
. O
01 O
) O
, O
and O
death O
, O
90 O
% O
( O
P O
< O
or O
= O
. O
05 O
) O
, O
compared O
with O
group O
4 O
. O

CONCLUSION O
: O
Flumazenil B
can O
unmask O
seizures O
and O
increase O
the O
incidence O
of O
death O
in O
a O
model O
of O
combined O
cocaine B
- O
diazepam B
intoxications O
. O

Mechanisms O
for O
protective O
effects O
of O
free O
radical O
scavengers O
on O
gentamicin B
- O
mediated O
nephropathy O
in O
rats O
. O

Studies O
were O
performed O
to O
examine O
the O
mechanisms O
for O
the O
protective O
effects O
of O
free O
radical O
scavengers O
on O
gentamicin B
( O
GM B
) O
- O
mediated O
nephropathy O
. O

Administration O
of O
GM B
at O
40 O
mg O
/ O
kg O
sc O
for O
13 O
days O
to O
rats O
induced O
a O
significant O
reduction O
in O
renal O
blood O
flow O
( O
RBF O
) O
and O
inulin O
clearance O
( O
CIn O
) O
as O
well O
as O
marked O
tubular O
damage O
. O

A O
significant O
reduction O
in O
urinary O
guanosine B
3 I
' I
, I
5 I
' I
- I
cyclic I
monophosphate I
( O
cGMP B
) O
excretion O
and O
a O
significant O
increase O
in O
renal O
cortical O
renin O
and O
endothelin O
- O
1 O
contents O
were O
also O
observed O
in O
GM B
- O
mediated O
nephropathy O
. O

Superoxide B
dismutase O
( O
SOD O
) O
or O
dimethylthiourea B
( O
DMTU B
) O
significantly O
lessened O
the O
GM B
- O
induced O
decrement O
in O
CIn O
. O

The O
SOD O
- O
induced O
increase O
in O
glomerular O
filtration O
rate O
was O
associated O
with O
a O
marked O
improvement O
in O
RBF O
, O
an O
increase O
in O
urinary O
cGMP B
excretion O
, O
and O
a O
decrease O
in O
renal O
renin O
and O
endothelin O
- O
1 O
content O
. O

SOD O
did O
not O
attenuate O
the O
tubular O
damage O
. O

In O
contrast O
, O
DMTU B
significantly O
reduced O
the O
tubular O
damage O
and O
lipid O
peroxidation O
, O
but O
it O
did O
not O
affect O
renal O
hemodynamics O
and O
vasoactive O
substances O
. O

Neither O
SOD O
nor O
DMTU B
affected O
the O
renal O
cortical O
GM B
content O
in O
GM B
- O
treated O
rats O
. O

These O
results O
suggest O
that O
1 O
) O
both O
SOD O
and O
DMTU B
have O
protective O
effects O
on O
GM B
- O
mediated O
nephropathy O
, O
2 O
) O
the O
mechanisms O
for O
the O
protective O
effects O
differ O
for O
SOD O
and O
DMTU B
, O
and O
3 O
) O
superoxide B
anions O
play O
a O
critical O
role O
in O
GM B
- O
induced O
renal O
vasoconstriction O
. O

Cephalothin B
- O
induced O
immune O
hemolytic O
anemia O
. O

A O
patient O
with O
renal O
disease O
developed O
Coombs O
- O
positive O
hemolytic O
anemia O
while O
receiving O
cephalothin B
therapy O
. O

An O
anti O
- O
cephalothin B
IgG O
antibody O
was O
detected O
in O
the O
patient O
' O
s O
serum O
and O
in O
the O
eluates O
from O
her O
erythrocytes O
. O

In O
addition O
, O
nonimmunologic O
binding O
of O
normal O
and O
patient O
' O
s O
serum O
proteins O
to O
her O
own O
and O
cephalothin B
- O
coated O
normal O
red O
cells O
was O
demonstrated O
. O

Skin O
tests O
and O
in O
vitro O
lymphocyte O
stimulation O
revealed O
that O
the O
patient O
was O
sensitized O
to O
cephalothin B
and O
also O
to O
ampicillin B
. O

Careful O
investigation O
of O
drug O
- O
induced O
hemolytic O
anemias O
reveals O
the O
complexity O
of O
the O
immune O
mechanisms O
involved O
. O

Assessment O
of O
cardiomyocyte O
DNA O
synthesis O
during O
hypertrophy O
in O
adult O
mice O
. O

The O
ability O
of O
cardiomyocytes O
to O
synthesize O
DNA O
in O
response O
to O
experimentally O
induced O
cardiac O
hypertrophy O
was O
assessed O
in O
adult O
mice O
. O

Isoproterenol B
delivered O
by O
osmotic O
minipump O
implantation O
in O
adult O
C3Heb O
/ O
FeJ O
mice O
resulted O
in O
a O
46 O
% O
increase O
in O
heart O
weight O
and O
a O
19 O
. O
3 O
% O
increase O
in O
cardiomyocyte O
area O
. O

No O
DNA O
synthesis O
, O
as O
assessed O
by O
autoradiographic O
analysis O
of O
isolated O
cardiomyocytes O
, O
was O
observed O
in O
control O
or O
hypertrophic O
hearts O
. O

A O
survey O
of O
15 O
independent O
inbred O
strains O
of O
mice O
revealed O
that O
ventricular O
cardiomyocyte O
nuclear O
number O
ranged O
from O
3 O
to O
13 O
% O
mononucleate O
, O
suggesting O
that O
cardiomyocyte O
terminal O
differentiation O
is O
influenced O
directly O
or O
indirectly O
by O
genetic O
background O
. O

To O
determine O
whether O
the O
capacity O
for O
reactive O
DNA O
synthesis O
was O
also O
subject O
to O
genetic O
regulation O
, O
cardiac O
hypertrophy O
was O
induced O
in O
the O
strains O
of O
mice O
comprising O
the O
extremes O
of O
the O
nuclear O
number O
survey O
. O

These O
data O
indicate O
that O
adult O
mouse O
atrial O
and O
ventricular O
cardiomyocytes O
do O
not O
synthesize O
DNA O
in O
response O
to O
isoproterenol B
- O
induced O
cardiac O
hypertrophy O
. O

Central O
cardiovascular O
effects O
of O
AVP B
and O
ANP O
in O
normotensive O
and O
spontaneously O
hypertensive O
rats O
. O

The O
purpose O
of O
the O
present O
study O
was O
to O
compare O
influence O
of O
central O
arginine B
vasopressin I
( O
AVP B
) O
and O
of O
atrial O
natriuretic O
peptide O
( O
ANP O
) O
on O
control O
of O
arterial O
blood O
pressure O
( O
MAP O
) O
and O
heart O
rate O
( O
HR O
) O
in O
normotensive O
( O
WKY O
) O
and O
spontaneously O
hypertensive O
( O
SHR O
) O
rats O
. O

Three O
series O
of O
experiments O
were O
performed O
on O
30 O
WKY O
and O
30 O
SHR O
, O
chronically O
instrumented O
with O
guide O
tubes O
in O
the O
lateral O
ventricle O
( O
LV O
) O
and O
arterial O
and O
venous O
catheters O
. O

MAP O
and O
HR O
were O
monitored O
before O
and O
after O
i O
. O
v O
. O
injections O
of O
either O
vehicle O
or O
1 O
, O
10 O
and O
50 O
ng O
of O
AVP B
and O
25 O
, O
125 O
and O
500 O
ng O
of O
ANP O
. O

Sensitivity O
of O
cardiac O
component O
of O
baroreflex O
( O
CCB O
) O
, O
expressed O
as O
a O
slope O
of O
the O
regression O
line O
was O
determined O
from O
relationships O
between O
systolic O
arterial O
pressure O
( O
SAP O
) O
and O
HR O
period O
( O
HRp O
) O
during O
phenylephrine B
( O
Phe B
) O
- O
induced O
hypertension O
and O
sodium B
nitroprusside I
( O
SN B
) O
- O
induced O
hypotension O
. O

CCB B
was O
measured O
before O
and O
after O
administration O
of O
either O
vehicle O
, O
AVP B
, O
ANP O
, O
or O
both O
peptides O
together O
. O

Increases O
of O
MAP O
occurred O
after O
LV O
administration O
of O
1 O
, O
10 O
and O
50 O
ng O
of O
AVP B
in O
WKY O
and O
of O
10 O
and O
50 O
ng O
in O
SHR O
. O

ANP O
did O
not O
cause O
significant O
changes O
in O
MAP O
in O
both O
strains O
as O
compared O
to O
vehicle O
, O
but O
it O
abolished O
AVP B
- O
induced O
MAP O
increase O
in O
WKY O
and O
SHR O
. O

CCB O
was O
reduced O
in O
WKY O
and O
SHR O
after O
LV O
administration O
of O
AVP B
during O
SN B
- O
induced O
hypotension O
. O

In O
SHR O
but O
not O
in O
WKY O
administration O
of O
ANP O
, O
AVP B
and O
ANP O
+ O
AVP B
decreased O
CCB B
during O
Phe B
- O
induced O
MAP O
elevation O
. O

The O
results O
indicate O
that O
centrally O
applied O
AVP B
and O
ANP O
exert O
differential O
effects O
on O
blood O
pressure O
and O
baroreflex O
control O
of O
heart O
rate O
in O
WKY O
and O
SHR O
and O
suggest O
interaction O
of O
these O
two O
peptides O
in O
blood O
pressure O
regulation O
at O
the O
level O
of O
central O
nervous O
system O
. O

Cutaneous O
exposure O
to O
warfarin B
- O
like O
anticoagulant O
causing O
an O
intracerebral O
hemorrhage O
: O
a O
case O
report O
. O

A O
case O
of O
intercerebral O
hematoma O
due O
to O
warfarin B
- O
induced O
coagulopathy O
is O
presented O
. O

The O
39 O
- O
year O
- O
old O
woman O
had O
spread O
a O
warfarin B
- O
type O
rat O
poison O
around O
her O
house O
weekly O
using O
her O
bare O
hands O
, O
with O
no O
washing O
post O
application O
. O

Percutaneous O
absorption O
of O
warfarin B
causing O
coagulopathy O
, O
reported O
three O
times O
in O
the O
past O
, O
is O
a O
significant O
risk O
if O
protective O
measures O
, O
such O
as O
gloves O
, O
are O
not O
used O
. O

An O
adverse O
drug O
interaction O
with O
piroxicam B
, O
which O
she O
took O
occasionally O
, O
may O
have O
exacerbated O
the O
coagulopathy O
. O

Pediatric O
heart O
transplantation O
without O
chronic O
maintenance O
steroids B
. O

From O
1986 O
to O
February O
1993 O
, O
40 O
children O
aged O
2 O
months O
to O
18 O
years O
( O
average O
age O
10 O
. O
4 O
+ O
/ O
- O
5 O
. O
8 O
years O
) O
underwent O
heart O
transplantation O
. O

Indications O
for O
transplantation O
were O
idiopathic O
cardiomyopathy O
( O
52 O
% O
) O
, O
congenital O
heart O
disease O
( O
35 O
% O
) O
with O
and O
without O
prior O
repair O
( O
71 O
% O
and O
29 O
% O
, O
respectively O
) O
, O
hypertrophic O
cardiomyopathy O
( O
5 O
% O
) O
, O
valvular O
heart O
disease O
( O
3 O
% O
) O
, O
and O
doxorubicin B
cardiomyopathy O
( O
5 O
% O
) O
. O

Patients O
were O
managed O
with O
cyclosporine B
and O
azathioprine B
. O

No O
prophylaxis O
with O
antilymphocyte O
globulin O
was O
used O
. O

Steroids B
were O
given O
to O
39 O
% O
of O
patients O
for O
refractory O
rejection O
, O
but O
weaning O
was O
always O
attempted O
and O
generally O
successful O
( O
64 O
% O
) O
. O

Five O
patients O
( O
14 O
% O
) O
received O
maintenance O
steroids B
. O

Four O
patients O
died O
in O
the O
perioperative O
period O
and O
one O
died O
4 O
months O
later O
. O

There O
have O
been O
no O
deaths O
related O
to O
rejection O
or O
infection O
. O

Average O
follow O
- O
up O
was O
36 O
+ O
/ O
- O
19 O
months O
( O
range O
1 O
to O
65 O
months O
) O
. O

Cumulative O
survival O
is O
88 O
% O
at O
5 O
years O
. O

In O
patients O
less O
than O
7 O
years O
of O
age O
, O
rejection O
was O
monitored O
noninvasively O
. O

In O
the O
first O
postoperative O
month O
, O
89 O
% O
of O
patients O
were O
treated O
for O
rejection O
. O

Freedom O
from O
serious O
infections O
was O
83 O
% O
at O
1 O
month O
and O
65 O
% O
at O
1 O
year O
. O

Cytomegalovirus O
infections O
were O
treated O
successfully O
with O
ganciclovir B
in O
11 O
patients O
. O

No O
impairment O
of O
growth O
was O
observed O
in O
children O
who O
underwent O
transplantation O
compared O
with O
a O
control O
population O
. O

Twenty O
- O
one O
patients O
( O
60 O
% O
) O
have O
undergone O
annual O
catheterizations O
and O
no O
sign O
of O
graft O
atherosclerosis O
has O
been O
observed O
. O

Seizures O
occurred O
in O
five O
patients O
( O
14 O
% O
) O
and O
hypertension O
was O
treated O
in O
10 O
patients O
( O
28 O
% O
) O
. O

No O
patient O
was O
disabled O
and O
no O
lymphoproliferative O
disorder O
was O
observed O
. O
( O
ABSTRACT O
TRUNCATED O
AT O
250 O
WORDS O
) O

Delirium O
during O
fluoxetine B
treatment O
. O

A O
case O
report O
. O

The O
correlation O
between O
high O
serum O
tricyclic O
antidepressant B
concentrations O
and O
central O
nervous O
system O
side O
effects O
has O
been O
well O
established O
. O

Only O
a O
few O
reports O
exist O
, O
however O
, O
on O
the O
relationship O
between O
the O
serum O
concentrations O
of O
selective O
serotonin B
reuptake O
inhibitors O
( O
SSRIs B
) O
and O
their O
toxic O
effects O
. O

In O
some O
cases O
, O
a O
high O
serum O
concentration O
of O
citalopram B
( O
> O
600 O
nmol O
/ O
L O
) O
in O
elderly O
patients O
has O
been O
associated O
with O
increased O
somnolence O
and O
movement O
difficulties O
. O

Widespread O
cognitive O
disorders O
, O
such O
as O
delirium O
, O
have O
not O
been O
previously O
linked O
with O
high O
blood O
levels O
of O
SSRIs B
. O

In O
this O
report O
, O
we O
describe O
a O
patient O
with O
acute O
hyperkinetic O
delirium O
connected O
with O
a O
high O
serum O
total O
fluoxetine B
( O
fluoxetine B
plus O
desmethylfluoxetine B
) O
concentration O
. O

Pulmonary O
edema O
and O
shock O
after O
high O
- O
dose O
aracytine B
- I
C I
for O
lymphoma O
; O
possible O
role O
of O
TNF O
- O
alpha O
and O
PAF O
. O

Four O
out O
of O
23 O
consecutive O
patients O
treated O
with O
high O
- O
dose O
Ara B
- I
C I
for O
lymphomas O
in O
our O
institution O
developed O
a O
strikingly O
similar O
syndrome O
during O
the O
perfusion O
. O

It O
was O
characterized O
by O
the O
onset O
of O
fever O
, O
diarrhea O
, O
shock O
, O
pulmonary O
edema O
, O
acute O
renal O
failure O
, O
metabolic O
acidosis O
, O
weight O
gain O
and O
leukocytosis O
. O

Thorough O
bacteriological O
screening O
failed O
to O
provide O
evidence O
of O
infection O
. O

Sequential O
biological O
assays O
of O
IL O
- O
1 O
, O
IL O
- O
2 O
, O
TNF O
and O
PAF O
were O
performed O
during O
Ara B
- I
C I
infusion O
to O
ten O
patients O
, O
including O
the O
four O
who O
developed O
the O
syndrome O
. O

TNF O
and O
PAF O
activity O
was O
found O
in O
the O
serum O
of O
respectively O
two O
and O
four O
of O
the O
cases O
, O
but O
not O
in O
the O
six O
controls O
. O

As O
TNF O
and O
PAF O
are O
thought O
to O
be O
involved O
in O
the O
development O
of O
septic O
shock O
and O
adult O
respiratory O
distress O
syndrome O
, O
we O
hypothesize O
that O
high O
- O
dose O
Ara B
- I
C I
may O
be O
associated O
with O
cytokine O
release O
. O

Protective O
effect O
of O
clentiazem B
against O
epinephrine B
- O
induced O
cardiac O
injury O
in O
rats O
. O

We O
investigated O
the O
effects O
of O
clentiazem B
, O
a O
1 B
, I
5 I
- I
benzothiazepine I
calcium B
antagonist O
, O
on O
epinephrine B
- O
induced O
cardiomyopathy O
in O
rats O
. O

With O
2 O
- O
week O
chronic O
epinephrine B
infusion O
, O
16 O
of O
30 O
rats O
died O
within O
4 O
days O
, O
and O
severe O
ischemic O
lesions O
and O
fibrosis O
of O
the O
left O
ventricles O
were O
observed O
. O

In O
epinephrine B
- O
treated O
rats O
, O
left O
atrial O
and O
left O
ventricular O
papillary O
muscle O
contractile O
responses O
to O
isoproterenol B
were O
reduced O
, O
but O
responses O
to O
calcium B
were O
normal O
or O
enhanced O
compared O
to O
controls O
. O

Left O
ventricular O
alpha O
and O
beta O
adrenoceptor O
densities O
were O
also O
reduced O
compared O
to O
controls O
. O

Treatment O
with O
clentiazem B
prevented O
epinephrine B
- O
induced O
death O
( O
P O
< O
. O
05 O
) O
, O
and O
attenuated O
the O
ventricular O
ischemic O
lesions O
and O
fibrosis O
, O
in O
a O
dose O
- O
dependent O
manner O
. O

Left O
atrial O
and O
left O
ventricular O
papillary O
muscle O
contractile O
responses O
to O
isoproterenol B
were O
reduced O
compared O
to O
controls O
in O
groups O
treated O
with O
clentiazem B
alone O
, O
but O
combined O
with O
epinephrine B
, O
clentiazem B
restored O
left O
atrial O
responses O
and O
enhanced O
left O
ventricular O
papillary O
responses O
to O
isoproterenol B
. O

On O
the O
other O
hand O
clentiazem B
did O
not O
prevent O
epinephrine B
- O
induced O
down O
- O
regulation O
of O
alpha O
and O
beta O
adrenoceptors O
. O

Interestingly O
, O
clentiazem B
, O
infused O
alone O
, O
resulted O
in O
decreased O
adrenergic O
receptor O
densities O
in O
the O
left O
ventricle O
. O

Clentiazem B
also O
did O
not O
prevent O
the O
enhanced O
responses O
to O
calcium B
seen O
in O
the O
epinephrine B
- O
treated O
animals O
, O
although O
the O
high O
dose O
of O
clentiazem B
partially O
attenuated O
the O
maximal O
response O
to O
calcium B
compared O
to O
epinephrine B
- O
treated O
animals O
. O

In O
conclusion O
, O
clentiazem B
attenuated O
epinephrine B
- O
induced O
cardiac O
injury O
, O
possibly O
through O
its O
effect O
on O
the O
adrenergic O
pathway O
. O

Kaliuretic O
effect O
of O
L B
- I
dopa I
treatment O
in O
parkinsonian O
patients O
. O

Hypokalemia O
, O
sometimes O
severe O
, O
was O
observed O
in O
some O
L B
- I
dopa I
- O
treated O
parkinsonian O
patients O
. O

The O
influence O
of O
L B
- I
dopa I
on O
the O
renal O
excretion O
of O
potassium B
was O
studied O
in O
3 O
patients O
with O
hypokalemia O
and O
in O
5 O
normokalemic O
patients O
by O
determination O
of O
renal O
plasma O
flow O
, O
glomerular O
filtration O
rate O
, O
plasma O
concentration O
of O
potassium B
and O
sodium B
as O
well O
as O
urinary O
excretion O
of O
potassium B
, O
sodium B
and O
aldosterone B
. O

L B
- I
Dopa I
intake O
was O
found O
to O
cause O
an O
increased O
excretion O
of O
potassium B
, O
and O
sometimes O
also O
of O
sodium B
, O
in O
the O
hypokalemic O
but O
not O
in O
the O
normokalemic O
patients O
. O

This O
effect O
on O
the O
renal O
function O
could O
be O
prohibited O
by O
the O
administration O
of O
a O
peripheral O
dopa B
decarbodylase O
inhibitor O
. O

It O
is O
not O
known O
why O
this O
effect O
occurred O
in O
some O
individuals O
but O
not O
in O
others O
, O
but O
our O
results O
indicate O
a O
correlation O
between O
aldosterone B
production O
and O
this O
renal O
effect O
of O
L B
- I
dopa I
. O

Cocaine B
induced O
myocardial O
ischemia O
. O

We O
report O
a O
case O
of O
myocardial O
ischemia O
induced O
by O
cocaine B
. O

The O
ischemia O
probably O
induced O
by O
coronary O
artery O
spasm O
was O
reversed O
by O
nitroglycerin B
and O
calcium B
blocking O
agents O
. O

Doxorubicin B
- O
induced O
cardiotoxicity O
monitored O
by O
ECG O
in O
freely O
moving O
mice O
. O

A O
new O
model O
to O
test O
potential O
protectors O
. O

In O
laboratory O
animals O
, O
histology O
is O
most O
commonly O
used O
to O
study O
doxorubicin B
- O
induced O
cardiotoxicity O
. O

However O
, O
for O
monitoring O
during O
treatment O
, O
large O
numbers O
of O
animals O
are O
needed O
. O

Recently O
we O
developed O
a O
new O
method O
to O
measure O
ECG O
values O
in O
freely O
moving O
mice O
by O
telemetry O
. O

With O
this O
model O
we O
investigated O
the O
effect O
of O
chronic O
doxorubicin B
administration O
on O
the O
ECG O
of O
freely O
moving O
BALB O
/ O
c O
mice O
and O
the O
efficacy O
of O
ICRF B
- I
187 I
as O
a O
protective O
agent O
. O

The O
ST O
interval O
significantly O
widened O
from O
15 O
. O
0 O
+ O
/ O
- O
1 O
. O
5 O
to O
56 O
. O
8 O
+ O
/ O
- O
11 O
. O
8 O
ms O
in O
week O
10 O
( O
7 O
weekly O
doses O
of O
4 O
mg O
/ O
kg O
doxorubicin B
given O
i O
. O
v O
. O
plus O
3 O
weeks O
of O
observation O
) O
. O

The O
ECG O
of O
the O
control O
animals O
did O
not O
change O
during O
the O
entire O
study O
. O

After O
sacrifice O
the O
hearts O
of O
doxorubicin B
- O
treated O
animals O
were O
enlarged O
and O
the O
atria O
were O
hypertrophic O
. O

As O
this O
schedule O
exerted O
more O
toxicity O
than O
needed O
to O
investigate O
protective O
agents O
, O
the O
protection O
of O
ICRF B
- I
187 I
was O
determined O
using O
a O
dose O
schedule O
with O
lower O
general O
toxicity O
( O
6 O
weekly O
doses O
of O
4 O
mg O
/ O
kg O
doxorubicin B
given O
i O
. O
v O
. O
plus O
2 O
weeks O
of O
observation O
) O
. O

On O
this O
schedule O
, O
the O
animals O
' O
hearts O
appeared O
normal O
after O
sacrifice O
and O
ICRF B
- I
187 I
( O
50 O
mg O
/ O
kg O
given O
i O
. O
p O
. O
1 O
h O
before O
doxorubicin B
) O
provided O
almost O
full O
protection O
. O

These O
data O
were O
confirmed O
by O
histology O
. O

The O
results O
indicate O
that O
this O
new O
model O
is O
very O
sensitive O
and O
enables O
monitoring O
of O
the O
development O
of O
cardiotoxicity O
with O
time O
. O

These O
findings O
result O
in O
a O
model O
that O
allows O
the O
testing O
of O
protectors O
against O
doxorubicin B
- O
induced O
cardiotoxicity O
as O
demonstrated O
by O
the O
protection O
provided O
by O
ICRF B
- I
187 I
. O

Epinephrine B
dysrhythmogenicity O
is O
not O
enhanced O
by O
subtoxic O
bupivacaine B
in O
dogs O
. O

Since O
bupivacaine B
and O
epinephrine B
may O
both O
precipitate O
dysrhythmias O
, O
circulating O
bupivacaine B
during O
regional O
anesthesia O
could O
potentiate O
dysrhythmogenic O
effects O
of O
epinephrine B
. O

We O
therefore O
examined O
whether O
bupivacaine B
alters O
the O
dysrhythmogenicity O
of O
subsequent O
administration O
of O
epinephrine B
in O
conscious O
, O
healthy O
dogs O
and O
in O
anesthetized O
dogs O
with O
myocardial O
infarction O
. O

Forty O
- O
one O
conscious O
dogs O
received O
10 O
micrograms O
. O
kg O
- O
1 O
. O
min O
- O
1 O
epinephrine B
. O

Seventeen O
animals O
responded O
with O
ventricular O
tachycardia O
( O
VT O
) O
within O
3 O
min O
. O

After O
3 O
h O
, O
these O
responders O
randomly O
received O
1 O
or O
2 O
mg O
/ O
kg O
bupivacaine B
or O
saline O
over O
5 O
min O
, O
followed O
by O
10 O
micrograms O
. O
kg O
- O
1 O
. O
min O
- O
1 O
epinephrine B
. O

In O
the O
bupivacaine B
groups O
, O
epinephrine B
caused O
fewer O
prodysrhythmic O
effects O
than O
without O
bupivacaine B
. O

VT O
appeared O
in O
fewer O
dogs O
and O
at O
a O
later O
time O
, O
and O
there O
were O
more O
sinoatrial O
beats O
and O
less O
ectopies O
. O

Epinephrine B
shortened O
QT O
less O
after O
bupivacaine B
than O
in O
control O
animals O
. O

One O
day O
after O
experimental O
myocardial O
infarction O
, O
six O
additional O
halothane B
- O
anesthetized O
dogs O
received O
4 O
micrograms O
. O
kg O
- O
1 O
. O
min O
- O
1 O
epinephrine B
until O
VT O
appeared O
. O

After O
45 O
min O
, O
1 O
mg O
/ O
kg O
bupivacaine B
was O
injected O
over O
5 O
min O
, O
again O
followed O
by O
4 O
micrograms O
. O
kg O
- O
1 O
. O
min O
- O
1 O
epinephrine B
. O

In O
these O
dogs O
, O
the O
prodysrhythmic O
response O
to O
epinephrine B
was O
also O
mitigated O
by O
preceding O
bupivacaine B
. O

Bupivacaine B
antagonizes O
epinephrine B
dysrhythmogenicity O
in O
conscious O
dogs O
susceptible O
to O
VT O
and O
in O
anesthetized O
dogs O
with O
spontaneous O
postinfarct O
dysrhythmias O
. O

There O
is O
no O
evidence O
that O
systemic O
subtoxic O
bupivacaine B
administration O
enhances O
the O
dysrhythmogenicity O
of O
subsequent O
epinephrine B
. O

Milk O
- O
alkali O
syndrome O
induced O
by O
1 B
, I
25 I
( I
OH I
) I
2D I
in O
a O
patient O
with O
hypoparathyroidism O
. O

Milk O
- O
alkali O
syndrome O
was O
first O
described O
70 O
years O
ago O
in O
the O
context O
of O
the O
treatment O
of O
peptic O
ulcer O
disease O
with O
large O
amounts O
of O
calcium B
and O
alkali O
. O

Although O
with O
current O
ulcer O
therapy O
( O
H O
- O
2 O
blockers O
, O
omeprazole B
, O
and O
sucralfate B
) O
, O
the O
frequency O
of O
milk O
- O
alkali O
syndrome O
has O
decreased O
significantly O
, O
the O
classic O
triad O
of O
hypercalcemia O
, O
alkalosis O
, O
and O
renal O
impairment O
remains O
the O
hallmark O
of O
the O
syndrome O
. O

Milk O
- O
alkali O
syndrome O
can O
present O
serious O
and O
occasionally O
life O
- O
threatening O
illness O
unless O
diagnosed O
and O
treated O
appropriately O
. O

This O
article O
presents O
a O
patient O
with O
hypoparathyroidism O
who O
was O
treated O
with O
calcium B
carbonate I
and O
calcitriol B
resulting O
in O
two O
admissions O
to O
the O
hospital O
for O
milk O
- O
alkali O
syndrome O
. O

The O
patient O
was O
successfully O
treated O
with O
intravenous O
pamidronate B
on O
his O
first O
admission O
and O
with O
hydrocortisone B
on O
the O
second O
. O

This O
illustrates O
intravenous O
pamidronate B
as O
a O
valuable O
therapeutic O
tool O
when O
milk O
- O
alkali O
syndrome O
presents O
as O
hypercalcemic O
emergency O
. O

Famotidine B
- O
associated O
delirium O
. O

A O
series O
of O
six O
cases O
. O

Famotidine B
is O
a O
histamine B
H2 O
- O
receptor O
antagonist O
used O
in O
inpatient O
settings O
for O
prevention O
of O
stress O
ulcers O
and O
is O
showing O
increasing O
popularity O
because O
of O
its O
low O
cost O
. O

Although O
all O
of O
the O
currently O
available O
H2 O
- O
receptor O
antagonists O
have O
shown O
the O
propensity O
to O
cause O
delirium O
, O
only O
two O
previously O
reported O
cases O
have O
been O
associated O
with O
famotidine B
. O

The O
authors O
report O
on O
six O
cases O
of O
famotidine B
- O
associated O
delirium O
in O
hospitalized O
patients O
who O
cleared O
completely O
upon O
removal O
of O
famotidine B
. O

The O
pharmacokinetics O
of O
famotidine B
are O
reviewed O
, O
with O
no O
change O
in O
its O
metabolism O
in O
the O
elderly O
population O
seen O
. O

The O
implications O
of O
using O
famotidine B
in O
elderly O
persons O
are O
discussed O
. O

Encephalopathy O
during O
amitriptyline B
therapy O
: O
are O
neuroleptic O
malignant O
syndrome O
and O
serotonin O
syndrome O
spectrum O
disorders O
? O

This O
report O
describes O
a O
case O
of O
encephalopathy O
developed O
in O
the O
course O
of O
amitriptyline B
therapy O
, O
during O
a O
remission O
of O
unipolar O
depression O
. O

This O
patient O
could O
have O
been O
diagnosed O
as O
having O
either O
neuroleptic O
malignant O
syndrome O
( O
NMS O
) O
or O
serotonin O
syndrome O
( O
SS O
) O
. O

The O
major O
determinant O
of O
the O
symptoms O
may O
have O
been O
dopamine B
/ O
serotonin B
imbalance O
in O
the O
central O
nervous O
system O
. O

The O
NMS O
- O
like O
encephalopathy O
that O
develops O
in O
association O
with O
the O
use O
of O
antidepressants B
indicates O
that O
NMS O
and O
SS O
are O
spectrum O
disorders O
induced O
by O
drugs O
with O
both O
antidopaminergic O
and O
serotonergic O
effects O
. O

Genetic O
separation O
of O
tumor O
growth O
and O
hemorrhagic O
phenotypes O
in O
an O
estrogen B
- O
induced O
tumor O
. O

Chronic O
administration O
of O
estrogen B
to O
the O
Fischer O
344 O
( O
F344 O
) O
rat O
induces O
growth O
of O
large O
, O
hemorrhagic O
pituitary O
tumors O
. O

Ten O
weeks O
of O
diethylstilbestrol B
( O
DES B
) O
treatment O
caused O
female O
F344 O
rat O
pituitaries O
to O
grow O
to O
an O
average O
of O
109 O
. O
2 O
+ O
/ O
- O
6 O
. O
3 O
mg O
( O
mean O
+ O
/ O
- O
SE O
) O
versus O
11 O
. O
3 O
+ O
/ O
- O
1 O
. O
4 O
mg O
for O
untreated O
rats O
, O
and O
to O
become O
highly O
hemorrhagic O
. O

The O
same O
DES B
treatment O
produced O
no O
significant O
growth O
( O
8 O
. O
9 O
+ O
/ O
- O
0 O
. O
5 O
mg O
for O
treated O
females O
versus O
8 O
. O
7 O
+ O
/ O
- O
1 O
. O
1 O
for O
untreated O
females O
) O
or O
morphological O
changes O
in O
Brown O
Norway O
( O
BN O
) O
rat O
pituitaries O
. O

An O
F1 O
hybrid O
of O
F344 O
and O
BN O
exhibited O
significant O
pituitary O
growth O
after O
10 O
weeks O
of O
DES B
treatment O
with O
an O
average O
mass O
of O
26 O
. O
3 O
+ O
/ O
- O
0 O
. O
7 O
mg O
compared O
with O
8 O
. O
6 O
+ O
/ O
- O
0 O
. O
9 O
mg O
for O
untreated O
rats O
. O

Surprisingly O
, O
the O
F1 O
hybrid O
tumors O
were O
not O
hemorrhagic O
and O
had O
hemoglobin O
content O
and O
outward O
appearance O
identical O
to O
that O
of O
BN O
. O

Expression O
of O
both O
growth O
and O
morphological O
changes O
is O
due O
to O
multiple O
genes O
. O

However O
, O
while O
DES B
- O
induced O
pituitary O
growth O
exhibited O
quantitative O
, O
additive O
inheritance O
, O
the O
hemorrhagic O
phenotype O
exhibited O
recessive O
, O
epistatic O
inheritance O
. O

Only O
5 O
of O
the O
160 O
F2 O
pituitaries O
exhibited O
the O
hemorrhagic O
phenotype O
; O
36 O
of O
the O
160 O
F2 O
pituitaries O
were O
in O
the O
F344 O
range O
of O
mass O
, O
but O
31 O
of O
these O
were O
not O
hemorrhagic O
, O
indicating O
that O
the O
hemorrhagic O
phenotype O
is O
not O
merely O
a O
consequence O
of O
extensive O
growth O
. O

The O
hemorrhagic O
F2 O
pituitaries O
were O
all O
among O
the O
most O
massive O
, O
indicating O
that O
some O
of O
the O
genes O
regulate O
both O
phenotypes O
. O

Increased O
expression O
of O
neuronal O
nitric B
oxide I
synthase O
in O
bladder O
afferent O
pathways O
following O
chronic O
bladder O
irritation O
. O

Immunocytochemical O
techniques O
were O
used O
to O
examine O
alterations O
in O
the O
expression O
of O
neuronal O
nitric B
oxide I
synthase O
( O
NOS O
) O
in O
bladder O
pathways O
following O
acute O
and O
chronic O
irritation O
of O
the O
urinary O
tract O
of O
the O
rat O
. O

Chemical O
cystitis O
was O
induced O
by O
cyclophosphamide B
( O
CYP B
) O
which O
is O
metabolized O
to O
acrolein B
, O
an O
irritant O
eliminated O
in O
the O
urine O
. O

Injection O
of O
CYP B
( O
n O
= O
10 O
, O
75 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
2 O
hours O
prior O
to O
perfusion O
( O
acute O
treatment O
) O
of O
the O
animals O
increased O
Fos O
- O
immunoreactivity O
( O
IR O
) O
in O
neurons O
in O
the O
dorsal O
commissure O
, O
dorsal O
horn O
, O
and O
autonomic O
regions O
of O
spinal O
segments O
( O
L1 O
- O
L2 O
and O
L6 O
- O
S1 O
) O
which O
receive O
afferent O
inputs O
from O
the O
bladder O
, O
urethra O
, O
and O
ureter O
. O

Fos O
- O
IR O
in O
the O
spinal O
cord O
was O
not O
changed O
in O
rats O
receiving O
chronic O
CYP B
treatment O
( O
n O
= O
15 O
, O
75 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
, O
every O
3rd O
day O
for O
2 O
weeks O
) O
. O

In O
control O
animals O
and O
in O
animals O
treated O
acutely O
with O
CYP B
, O
only O
small O
numbers O
of O
NOS O
- O
IR O
cells O
( O
0 O
. O
5 O
- O
0 O
. O
7 O
cell O
profiles O
/ O
sections O
) O
were O
detected O
in O
the O
L6 O
- O
S1 O
dorsal O
root O
ganglia O
( O
DRG O
) O
. O

Chronic O
CYP B
administration O
significantly O
( O
P O
< O
or O
= O
. O
002 O
) O
increased O
bladder O
weight O
by O
60 O
% O
and O
increased O
( O
7 O
- O
to O
11 O
- O
fold O
) O
the O
numbers O
of O
NOS O
- O
immunoreactive O
( O
IR O
) O
afferent O
neurons O
in O
the O
L6 O
- O
S1 O
DRG O
. O

A O
small O
increase O
( O
1 O
. O
5 O
- O
fold O
) O
also O
occurred O
in O
the O
L1 O
DRG O
, O
but O
no O
change O
was O
detected O
in O
the O
L2 O
and O
L5 O
DRG O
. O

Bladder O
afferent O
cells O
in O
the O
L6 O
- O
S1 O
DRG O
labeled O
by O
Fluorogold B
( O
40 O
microliters O
) O
injected O
into O
the O
bladder O
wall O
did O
not O
exhibit O
NOS O
- O
IR O
in O
control O
animals O
; O
however O
, O
following O
chronic O
CYP B
administration O
, O
a O
significant O
percentage O
of O
bladder O
afferent O
neurons O
were O
NOS O
- O
IR O
: O
L6 O
( O
19 O
. O
8 O
+ O
/ O
- O
4 O
. O
6 O
% O
) O
and O
S1 O
( O
25 O
. O
3 O
+ O
/ O
- O
2 O
. O
9 O
% O
) O
. O

These O
results O
indicate O
that O
neuronal O
gene O
expression O
in O
visceral O
sensory O
pathways O
can O
be O
upregulated O
by O
chemical O
irritation O
of O
afferent O
receptors O
in O
the O
urinary O
tract O
and O
/ O
or O
that O
pathological O
changes O
in O
the O
urinary O
tract O
can O
initiate O
chemical O
signals O
that O
alter O
the O
chemical O
properties O
of O
visceral O
afferent O
neurons O
. O

Effects O
of O
a O
new O
calcium B
antagonist O
, O
CD B
- I
832 I
, O
on O
isoproterenol B
- O
induced O
myocardial O
ischemia O
in O
dogs O
with O
partial O
coronary O
stenosis O
. O

Effects O
of O
CD B
- I
832 I
on O
isoproterenol B
( O
ISO B
) O
- O
induced O
myocardial O
ischemia O
were O
studied O
in O
dogs O
with O
partial O
coronary O
stenosis O
of O
the O
left O
circumflex O
coronary O
artery O
and O
findings O
were O
compared O
with O
those O
for O
nifedipine B
or O
diltiazem B
. O

In O
the O
presence O
of O
coronary O
artery O
stenosis O
, O
3 O
- O
min O
periods O
of O
intracoronary O
ISO B
infusion O
( O
10 O
ng O
/ O
kg O
/ O
min O
) O
increased O
heart O
rate O
and O
maximal O
rate O
of O
left O
ventricular O
pressure O
rise O
, O
which O
resulted O
in O
a O
decrease O
in O
percentage O
segmental O
shortening O
and O
ST O
- O
segment O
elevation O
of O
the O
epicardial O
electrocardiogram O
. O

After O
the O
control O
ISO B
infusion O
with O
stenosis O
was O
performed O
, O
equihypotensive O
doses O
of O
CD B
- I
832 I
( O
3 O
and O
10 O
micrograms O
/ O
kg O
/ O
min O
, O
n O
= O
7 O
) O
, O
nifedipine B
( O
1 O
and O
3 O
micrograms O
/ O
kg O
/ O
min O
, O
n O
= O
9 O
) O
or O
diltiazem B
( O
10 O
and O
30 O
micrograms O
/ O
kg O
/ O
min O
, O
n O
= O
7 O
) O
were O
infused O
5 O
min O
before O
and O
during O
the O
second O
and O
third O
ISO B
infusion O
. O

Both O
CD B
- I
832 I
and O
diltiazem B
, O
but O
not O
nifedipine B
, O
significantly O
reduced O
the O
increase O
in O
heart O
rate O
induced O
by O
ISO B
infusion O
. O

In O
contrast O
to O
nifedipine B
, O
CD B
- I
832 I
( O
10 O
micrograms O
/ O
kg O
/ O
min O
) O
prevented O
the O
decrease O
in O
percentage O
segmental O
shortening O
from O
32 O
+ O
/ O
- O
12 O
% O
to O
115 O
+ O
/ O
- O
26 O
% O
of O
the O
control O
value O
( O
P O
< O
. O
01 O
) O
and O
ST O
- O
segment O
elevation O
from O
5 O
. O
6 O
+ O
/ O
- O
1 O
. O
0 O
mV O
to O
1 O
. O
6 O
+ O
/ O
- O
1 O
. O
3 O
mV O
( O
P O
< O
. O
01 O
) O
at O
3 O
min O
after O
ISO B
infusion O
with O
stenosis O
. O

Diltiazem B
( O
30 O
micrograms O
/ O
kg O
/ O
min O
) O
also O
prevented O
the O
decrease O
in O
percentage O
segmental O
shortening O
from O
34 O
+ O
/ O
- O
14 O
% O
to O
63 O
+ O
/ O
- O
18 O
% O
of O
the O
control O
value O
( O
P O
< O
. O
05 O
) O
and O
ST O
- O
segment O
elevation O
from O
4 O
. O
7 O
+ O
/ O
- O
0 O
. O
7 O
mV O
to O
2 O
. O
1 O
+ O
/ O
- O
0 O
. O
7 O
mV O
( O
P O
< O
. O
01 O
) O
at O
3 O
min O
after O
ISO B
infusion O
with O
stenosis O
. O

These O
data O
show O
that O
CD B
- I
832 I
improves O
myocardial O
ischemia O
during O
ISO B
infusion O
with O
stenosis O
and O
suggest O
that O
the O
negative O
chronotropic O
property O
of O
CD B
- I
832 I
plays O
a O
major O
role O
in O
the O
beneficial O
effects O
of O
CD B
- I
832 I
. O

The O
effect O
of O
recombinant O
human O
insulin O
- O
like O
growth O
factor O
- O
I O
on O
chronic O
puromycin B
aminonucleoside I
nephropathy O
in O
rats O
. O

We O
recently O
demonstrated O
that O
recombinant O
hGH O
exacerbates O
renal O
functional O
and O
structural O
injury O
in O
chronic O
puromycin B
aminonucleoside I
( O
PAN B
) O
nephropathy O
, O
an O
experimental O
model O
of O
glomerular O
disease O
. O

Therefore O
, O
we O
examined O
whether O
recombinant O
human O
( O
rh O
) O
IGF O
- O
I O
is O
a O
safer O
alternative O
for O
the O
treatment O
of O
growth O
failure O
in O
rats O
with O
chronic O
PAN B
nephropathy O
. O

The O
glomerulopathy O
was O
induced O
by O
seven O
serial O
injections O
of O
PAN B
over O
12 O
wk O
. O

Experimental O
animals O
( O
n O
= O
6 O
) O
received O
rhIGF B
- I
I I
, O
400 O
micrograms O
/ O
d O
, O
whereas O
control O
rats O
( O
n O
= O
6 O
) O
received O
the O
vehicle O
. O

rhIGF O
- O
I O
improved O
weight O
gain O
by O
14 O
% O
( O
p O
< O
0 O
. O
05 O
) O
, O
without O
altering O
hematocrit O
or O
blood O
pressure O
in O
rats O
with O
renal O
disease O
. O

Urinary O
protein O
excretion O
was O
unaltered O
by O
rhIGF B
- I
I I
treatment O
in O
rats O
with O
chronic O
PAN B
nephropathy O
. O

After O
12 O
wk O
, O
the O
inulin O
clearance O
was O
higher O
in O
rhIGF O
- O
I O
- O
treated O
rats O
, O
0 O
. O
48 O
+ O
/ O
- O
0 O
. O
08 O
versus O
0 O
. O
24 O
+ O
/ O
- O
0 O
. O
06 O
mL O
/ O
min O
/ O
100 O
g O
of O
body O
weight O
in O
untreated O
PAN B
nephropathy O
animals O
, O
p O
< O
0 O
. O
05 O
. O

The O
improvement O
in O
GFR O
was O
not O
associated O
with O
enhanced O
glomerular O
hypertrophy O
or O
increased O
segmental O
glomerulosclerosis O
, O
tubulointerstitial O
injury O
, O
or O
renal O
cortical O
malondialdehyde B
content O
. O

In O
rats O
with O
PAN B
nephropathy O
, O
administration O
of O
rhIGF O
- O
I O
increased O
IGF O
- O
I O
and O
GH O
receptor O
gene O
expression O
, O
without O
altering O
the O
steady O
state O
level O
of O
IGF O
- O
I O
receptor O
mRNA O
. O

In O
normal O
rats O
with O
intact O
kidneys O
, O
rhIGF B
- I
I I
administration O
( O
n O
= O
4 O
) O
did O
not O
alter O
weight O
gain O
, O
blood O
pressure O
, O
proteinuria O
, O
GFR O
, O
glomerular O
planar O
area O
, O
renal O
cortical O
malondialdehyde B
content O
, O
or O
glomerular O
or O
tubulointerstitial O
damage O
, O
compared O
with O
untreated O
animals O
( O
n O
= O
4 O
) O
. O

rhIGF O
- O
I O
treatment O
reduced O
the O
steady O
state O
renal O
IGF O
- O
I O
mRNA O
level O
but O
did O
not O
modify O
gene O
expression O
of O
the O
IGF O
- O
I O
or O
GH O
receptors O
. O

We O
conclude O
that O
: O
1 O
) O
administration O
of O
rhIGF O
- O
I O
improves O
growth O
and O
GFR O
in O
rats O
with O
chronic O
PAN B
nephropathy O
and O
2 O
) O
unlike O
rhGH O
, O
long O
- O
term O
use O
of O
rhIGF O
- O
I O
does O
not O
worsen O
renal O
functional O
and O
structural O
injury O
in O
this O
disease O
model O
. O

Nefiracetam B
( O
DM B
- I
9384 I
) O
reverses O
apomorphine B
- O
induced O
amnesia O
of O
a O
passive O
avoidance O
response O
: O
delayed O
emergence O
of O
the O
memory O
retention O
effects O
. O

Nefiracetam B
is O
a O
novel O
pyrrolidone B
derivative O
which O
attenuates O
scopolamine B
- O
induced O
learning O
and O
post O
- O
training O
consolidation O
deficits O
. O

Given O
that O
apomorphine B
inhibits O
passive O
avoidance O
retention O
when O
given O
during O
training O
or O
in O
a O
defined O
10 O
- O
12h O
post O
- O
training O
period O
, O
we O
evaluated O
the O
ability O
of O
nefiracetam B
to O
attenuate O
amnesia O
induced O
by O
dopaminergic O
agonism O
. O

A O
step O
- O
down O
passive O
avoidance O
paradigm O
was O
employed O
and O
nefiracetam B
( O
3 O
mg O
/ O
kg O
) O
and O
apomorphine B
( O
0 O
. O
5 O
mg O
/ O
kg O
) O
were O
given O
alone O
or O
in O
combination O
during O
training O
and O
at O
the O
10 O
- O
12h O
post O
- O
training O
period O
of O
consolidation O
. O

Co O
- O
administration O
of O
nefiracetam B
and O
apomorphine B
during O
training O
or O
10h O
thereafter O
produced O
no O
significant O
anti O
- O
amnesic O
effect O
. O

However O
, O
administration O
of O
nefiracetam B
during O
training O
completely O
reversed O
the O
amnesia O
induced O
by O
apomorphine B
at O
the O
10h O
post O
- O
training O
time O
and O
the O
converse O
was O
also O
true O
. O

These O
effects O
were O
not O
mediated O
by O
a O
dopaminergic O
mechanism O
as O
nefiracetam B
, O
at O
millimolar O
concentrations O
, O
failed O
to O
displace O
either O
[ O
3H O
] O
SCH B
23390 I
or O
[ O
3H O
] O
spiperone B
binding O
from O
D1 O
or O
D2 O
dopamine B
receptor O
subtypes O
, O
respectively O
. O

It O
is O
suggested O
that O
nefiracetam B
augments O
molecular O
processes O
in O
the O
early O
stages O
of O
events O
which O
ultimately O
lead O
to O
consolidation O
of O
memory O
. O

Phenytoin B
encephalopathy O
as O
probable O
idiosyncratic O
reaction O
: O
case O
report O
. O

A O
case O
of O
phenytoin B
( O
DPH B
) O
encephalopathy O
with O
increasing O
seizures O
and O
EEG O
and O
mental O
changes O
is O
described O
. O

Despite O
adequate O
oral O
dosage O
of O
DPH B
( O
5 O
mg O
/ O
kg O
/ O
daily O
) O
the O
plasma O
level O
was O
very O
low O
( O
2 O
. O
8 O
microgramg O
/ O
ml O
) O
. O

The O
encephalopathy O
was O
probably O
an O
idiosyncratic O
and O
not O
toxic O
or O
allergic O
reaction O
. O

In O
fact O
the O
concentration O
of O
free O
DPH B
was O
normal O
, O
the O
patient O
presented O
a O
retarded O
morbilliform O
rash O
during O
DPH B
treatment O
, O
the O
protidogram O
was O
normal O
, O
and O
an O
intradermic O
DPH B
injection O
had O
no O
local O
effect O
. O

The O
authors O
conclude O
that O
in O
a O
patient O
starting O
DPH B
treatment O
an O
unexpected O
increase O
in O
seizures O
, O
with O
EEG O
and O
mental O
changes O
occurring O
simultaneously O
, O
should O
alert O
the O
physician O
to O
the O
possible O
need O
for O
eliminating O
DPH B
from O
the O
therapeutic O
regimen O
, O
even O
if O
plasma O
concentrations O
are O
low O
. O

Prevention O
and O
treatment O
of O
endometrial O
disease O
in O
climacteric O
women O
receiving O
oestrogen B
therapy O
. O

The O
treatment O
regimens O
are O
described O
in O
74 O
patients O
with O
endometrial O
disease O
among O
850 O
climacteric O
women O
receiving O
oestrogen B
therapy O
. O

Cystic O
hyperplasia O
was O
associated O
with O
unopposed O
oestrogen B
therapy O
without O
progestagen B
. O

Two O
courses O
of O
21 O
days O
of O
5 O
mg O
norethisterone B
daily O
caused O
reversion O
to O
normal O
in O
all O
57 O
cases O
of O
cystic O
hyperplasia O
and O
6 O
of O
the O
8 O
cases O
of O
atypical O
hyperplasia O
. O

4 O
cases O
of O
endometrial O
carcinoma O
referred O
from O
elsewhere O
demonstrated O
the O
problems O
of O
inappropriate O
and O
unsupervised O
unopposed O
oestrogen B
therapy O
and O
the O
difficulty O
in O
distinguishing O
severe O
hyperplasia O
from O
malignancy O
. O

Cyclical O
low O
- O
dose O
oestrogen B
therapy O
with O
7 O
- O
- O
13 O
days O
of O
progestagen B
does O
not O
seem O
to O
increase O
the O
risk O
of O
endometrial O
hyperplasia O
or O
carcinoma O
. O

Effects O
of O
exercise O
on O
the O
severity O
of O
isoproterenol B
- O
induced O
myocardial O
infarction O
. O

The O
effect O
of O
exercise O
on O
the O
severity O
of O
isoproterenol B
- O
induced O
myocardial O
infarction O
was O
studied O
in O
male O
rats O
. O

Ninety O
- O
three O
rats O
were O
randomly O
divided O
into O
three O
groups O
. O

The O
exercise O
- O
isoproterenol B
( O
E O
- O
1 O
) O
and O
exercise O
control O
( O
EC O
) O
groups O
exercised O
daily O
for O
thirty O
days O
on O
a O
treadmill O
at O
1 O
mph O
, O
2 O
% O
grade O
while O
animals O
of O
the O
sedentary O
- O
isoproterenol B
( O
S O
- O
I O
) O
group O
remained O
sedentary O
. O

Eight O
animals O
were O
assigned O
to O
the O
sedentary O
control O
( O
SC O
) O
group O
which O
remained O
sedentary O
throughout O
the O
experimental O
period O
. O

Forty O
- O
eight O
hours O
after O
the O
final O
exercise O
period O
, O
S O
- O
I O
and O
E O
- O
I O
animals O
received O
a O
single O
subcutaneous O
injection O
of O
isoproterenol B
( O
250 O
mg O
/ O
kg O
body O
weight O
) O
. O

Animals O
of O
the O
S O
- O
I O
group O
exhibited O
significantly O
( O
Pp O
less O
than O
0 O
. O
05 O
) O
greater O
mortality O
from O
the O
effects O
of O
isoproterenol B
than O
animals O
of O
the O
E B
- I
I O
group O
. O

Serum O
CPK O
activity O
for O
E B
- O
I O
animals O
was O
significantly O
( O
p O
less O
than O
0 O
. O
05 O
) O
greater O
than O
for O
animals O
in O
the O
S O
- O
I O
and O
EC O
groups O
twenty O
hours O
following O
isoproterenol B
injection O
. O

No O
statistically O
significant O
differences O
were O
observed O
between O
the O
two O
isoproterenol B
treated O
groups O
for O
severity O
of O
the O
induced O
lesions O
, O
changes O
in O
heart O
weight O
, O
or O
heart O
weight O
to O
body O
weight O
ratios O
. O

The O
results O
indicated O
that O
exercise O
reduced O
the O
mortality O
associated O
with O
the O
effects O
of O
large O
dosages O
of O
isoproterenol B
but O
had O
little O
on O
the O
severity O
of O
the O
infarction O
. O

Human O
corticotropin O
- O
releasing O
hormone O
and O
thyrotropin O
- O
releasing O
hormone O
modulate O
the O
hypercapnic O
ventilatory O
response O
in O
humans O
. O

Human O
corticotropin O
- O
releasing O
hormone O
( O
hCRH O
) O
and O
thyrotropin O
- O
releasing O
hormone O
( O
TRH B
) O
are O
known O
to O
stimulate O
ventilation O
after O
i O
. O
v O
. O
administration O
in O
humans O
. O

In O
a O
placebo O
- O
controlled O
, O
single O
- O
blind O
study O
we O
aimed O
to O
clarify O
if O
both O
peptides O
act O
by O
altering O
central O
chemosensitivity O
. O

Two O
subsequent O
CO2 B
- O
rebreathing O
tests O
were O
performed O
in O
healthy O
young O
volunteers O
. O

During O
the O
first O
test O
0 O
. O
9 O
% O
NaCl B
was O
given O
i O
. O
v O
. O
; O
during O
the O
second O
test O
200 O
micrograms O
of O
hCRH B
( O
n O
= O
12 O
) O
or O
400 O
micrograms O
of O
TRH B
( O
n O
= O
6 O
) O
was O
administered O
i O
. O
v O
. O
Nine O
subjects O
received O
0 O
. O
9 O
% O
NaCl B
i O
. O
v O
. O
during O
both O
rebreathing O
manoeuvres O
. O

The O
CO2 B
- O
response O
curves O
for O
the O
two O
tests O
were O
compared O
within O
the O
same O
subject O
. O

In O
the O
hCRH O
group O
a O
marked O
parallel O
shift O
of O
the O
CO2 B
- O
response O
curve O
to O
the O
left O
was O
observed O
after O
hCRH O
( O
P O
< O
0 O
. O
01 O
) O
. O

The O
same O
effect O
occurred O
following O
TRH B
but O
was O
less O
striking O
( O
P O
= O
0 O
. O
05 O
) O
. O

hCRH B
and O
TRH B
caused O
a O
reduction O
in O
the O
CO2 B
threshold O
. O

The O
CO2 B
- O
response O
curves O
in O
the O
control O
group O
were O
nearly O
identical O
. O

The O
results O
indicate O
an O
additive O
effect O
of O
both O
releasing O
hormones O
on O
the O
hypercapnic O
ventilatory O
response O
in O
humans O
, O
presumably O
independent O
of O
central O
chemosensitivity O
. O

Lamivudine B
is O
effective O
in O
suppressing O
hepatitis O
B O
virus O
DNA O
in O
Chinese O
hepatitis B
B I
surface I
antigen I
carriers O
: O
a O
placebo O
- O
controlled O
trial O
. O

Lamivudine B
is O
a O
novel O
2 B
' I
, I
3 I
' I
- I
dideoxy I
cytosine I
analogue O
that O
has O
potent O
inhibitory O
effects O
on O
hepatitis O
B O
virus O
replication O
in O
vitro O
and O
in O
vivo O
. O

We O
performed O
a O
single O
- O
blind O
, O
placebo O
- O
controlled O
study O
to O
assess O
its O
effectiveness O
and O
safety O
in O
Chinese O
hepatitis B
B I
surface I
antigen I
( O
HBsAg B
) O
carriers O
. O

Forty O
- O
two O
Chinese O
HBsAg B
carriers O
were O
randomized O
to O
receive O
placebo O
( O
6 O
patients O
) O
or O
lamivudine B
orally O
in O
dosages O
of O
25 O
mg O
, O
100 O
mg O
, O
or O
300 O
mg O
daily O
( O
12 O
patients O
for O
each O
dosage O
) O
. O

The O
drug O
was O
given O
for O
4 O
weeks O
. O

The O
patients O
were O
closely O
monitored O
clinically O
, O
biochemically O
, O
and O
serologically O
up O
to O
4 O
weeks O
after O
drug O
treatment O
. O

All O
36 O
patients O
receiving O
lamivudine B
had O
a O
decrease O
in O
hepatitis O
B O
virus O
( O
HBV O
) O
DNA O
values O
of O
> O
90 O
% O
( O
P O
< O
. O
001 O
compared O
with O
placebo O
) O
. O

Although O
25 O
mg O
of O
lamivudine B
was O
slightly O
less O
effective O
than O
100 O
mg O
( O
P O
= O
. O
011 O
) O
and O
300 O
mg O
( O
P O
= O
. O
005 O
) O
, O
it O
still O
induced O
94 O
% O
suppression O
of O
HBV O
DNA O
after O
the O
fourth O
week O
of O
therapy O
. O

HBV O
DNA O
values O
returned O
to O
pretreatment O
levels O
within O
4 O
weeks O
of O
cessation O
of O
therapy O
. O

There O
was O
no O
change O
in O
the O
hepatitis B
B I
e I
antigen I
status O
or O
in O
aminotransferase O
levels O
. O

No O
serious O
adverse O
events O
were O
observed O
. O

In O
conclusion O
, O
a O
4 O
- O
week O
course O
of O
lamivudine B
was O
safe O
and O
effective O
in O
suppression O
of O
HBV O
DNA O
in O
Chinese O
HBsAg B
carriers O
. O

The O
suppression O
was O
> O
90 O
% O
but O
reversible O
. O

Studies O
with O
long O
- O
term O
lamivudine B
administration O
should O
be O
performed O
to O
determine O
if O
prolonged O
suppression O
of O
HBV O
DNA O
can O
be O
achieved O
. O

Population O
- O
based O
study O
of O
risk O
of O
venous O
thromboembolism O
associated O
with O
various O
oral B
contraceptives I
. O

BACKGROUND O
: O
Four O
studies O
published O
since O
December O
, O
1995 O
, O
reported O
that O
the O
incidence O
of O
venous O
thromboembolism O
( O
VTE O
) O
was O
higher O
in O
women O
who O
used O
oral B
contraceptives I
( O
OCs B
) O
containing O
the O
third O
- O
generation O
progestagens B
gestodene B
or O
desogestrel B
than O
in O
users O
of O
OCs B
containing O
second O
- O
generation O
progestagens B
. O

However O
, O
confounding O
and O
bias O
in O
the O
design O
of O
these O
studies O
may O
have O
affected O
the O
findings O
. O

The O
aim O
of O
our O
study O
was O
to O
re O
- O
examine O
the O
association O
between O
risk O
of O
VTE O
and O
OC B
use O
with O
a O
different O
study O
design O
and O
analysis O
to O
avoid O
some O
of O
the O
bias O
and O
confounding O
of O
the O
earlier O
studies O
. O

METHODS O
: O
We O
used O
computer O
records O
of O
patients O
from O
143 O
general O
practices O
in O
the O
UK O
. O

The O
study O
was O
based O
on O
the O
medical O
records O
of O
about O
540 O
, O
000 O
women O
born O
between O
1941 O
and O
1981 O
. O

All O
women O
who O
had O
a O
recorded O
diagnosis O
of O
deep O
- O
vein O
thrombosis O
, O
venous O
thrombosis O
not O
otherwise O
specified O
, O
or O
pulmonary O
embolus O
during O
the O
study O
period O
, O
and O
who O
had O
been O
treated O
with O
an O
anticoagulant O
were O
identified O
as O
potential O
cases O
of O
VTE O
. O

We O
did O
a O
cohort O
analysis O
to O
estimate O
and O
compare O
incidence O
of O
VTE O
in O
users O
of O
the O
main O
OC B
preparations O
, O
and O
a O
nested O
case O
- O
control O
study O
to O
calculate O
the O
odds O
ratios O
of O
VTE O
associated O
with O
use O
of O
different O
types O
of O
OC B
, O
after O
adjustment O
for O
potential O
confounding O
factors O
. O

In O
the O
case O
- O
control O
study O
, O
we O
matched O
cases O
to O
controls O
by O
exact O
year O
of O
birth O
, O
practice O
, O
and O
current O
use O
of O
OCs B
. O

We O
used O
a O
multiple O
logistic O
regression O
model O
that O
included O
body O
- O
mass O
index O
, O
number O
of O
cycles O
, O
change O
in O
type O
of O
OC B
prescribed O
within O
3 O
months O
of O
the O
event O
, O
previous O
pregnancy O
, O
and O
concurrent O
disease O
. O

FINDINGS O
: O
85 O
women O
met O
the O
inclusion O
criteria O
for O
VTE O
, O
two O
of O
whom O
were O
users O
of O
progestagen B
- O
only O
OCs B
. O

Of O
the O
83 O
cases O
of O
VTE O
associated O
with O
use O
of O
combined O
OCs B
, O
43 O
were O
recorded O
as O
deep O
- O
vein O
thrombosis O
, O
35 O
as O
pulmonary O
thrombosis O
, O
and O
five O
as O
venous O
thrombosis O
not O
otherwise O
specified O
. O

The O
crude O
rate O
of O
VTE O
per O
10 O
, O
000 O
woman O
- O
years O
was O
4 O
. O
10 O
in O
current O
users O
of O
any O
OC B
, O
3 O
. O
10 O
in O
users O
of O
second O
- O
generation O
OCs B
, O
and O
4 O
. O
96 O
in O
users O
of O
third O
- O
generation O
preparations O
. O

After O
adjustment O
for O
age O
, O
the O
rate O
ratio O
of O
VTE O
in O
users O
of O
third O
- O
generation O
relative O
to O
second O
- O
generation O
OCs B
was O
1 O
. O
68 O
( O
95 O
% O
CI O
1 O
. O
04 O
- O
2 O
. O
75 O
) O
. O

Logistic O
regression O
showed O
no O
significant O
difference O
in O
the O
risk O
of O
VTE O
between O
users O
of O
third O
- O
generation O
and O
second O
- O
generation O
OCs B
. O

Among O
users O
of O
third O
- O
generation O
progestagens B
, O
the O
risk O
of O
VTE O
was O
higher O
in O
users O
of O
desogestrel B
with O
20 O
g O
ethinyloestradiol B
than O
in O
users O
of O
gestodene B
or O
desogestrel B
with O
30 O
g O
ethinyloestradiol B
. O

With O
all O
second O
- O
generation O
OCs B
as O
the O
reference O
, O
the O
odds O
ratios O
for O
VTE O
were O
3 O
. O
49 O
( O
1 O
. O
21 O
- O
10 O
. O
12 O
) O
for O
desogestrel B
plus O
20 O
g O
ethinyloestradiol B
and O
1 O
. O
18 O
( O
0 O
. O
66 O
- O
2 O
. O
17 O
) O
for O
the O
other O
third O
- O
generation O
progestagens B
. O

INTERPRETATION O
: O
The O
previously O
reported O
increase O
in O
odds O
ratio O
associated O
with O
third O
- O
generation O
OCs B
when O
compared O
with O
second O
- O
generation O
products O
is O
likely O
to O
have O
been O
the O
result O
of O
residual O
confounding O
by O
age O
. O

The O
increased O
odds O
ratio O
associated O
with O
products O
containing O
20 O
micrograms O
ethinyloestradiol B
and O
desogestrel B
compared O
with O
the O
30 O
micrograms O
product O
is O
biologically O
implausible O
, O
and O
is O
likely O
to O
be O
the O
result O
of O
preferential O
prescribing O
and O
, O
thus O
, O
confounding O
. O

MK B
- I
801 I
augments O
pilocarpine B
- O
induced O
electrographic O
seizure O
but O
protects O
against O
brain O
damage O
in O
rats O
. O

1 O
. O

The O
authors O
examined O
the O
anticonvulsant O
effects O
of O
MK B
- I
801 I
on O
the O
pilocarpine B
- O
induced O
seizure O
model O
. O

Intraperitoneal O
injection O
of O
pilocarpine B
( O
400 O
mg O
/ O
kg O
) O
induced O
tonic O
and O
clonic O
seizure O
. O

Scopolamine B
( O
10 O
mg O
/ O
kg O
) O
and O
pentobarbital B
( O
5 O
mg O
/ O
kg O
) O
prevented O
development O
of O
pilocarpine B
- O
induced O
behavioral O
seizure O
but O
MK B
- I
801 I
( O
0 O
. O
5 O
mg O
/ O
kg O
) O
did O
not O
. O

2 O
. O

An O
electrical O
seizure O
measured O
with O
hippocampal O
EEG O
appeared O
in O
the O
pilocarpine B
- O
treated O
group O
. O

Scopolamine B
and O
pentobarbital B
blocked O
the O
pilocarpine B
- O
induced O
electrographic O
seizure O
, O
MK B
- I
801 I
treatment O
augmented O
the O
electrographic O
seizure O
induced O
by O
pilocarpine B
. O

3 O
. O

Brain O
damage O
was O
assessed O
by O
examining O
the O
hippocampus O
microscopically O
. O

Pilocarpine B
produced O
neuronal O
death O
in O
the O
hippocampus O
, O
which O
showed O
pyknotic O
changes O
. O

Pentobarbital B
, O
scopolamine B
and O
MK B
- I
801 I
protected O
the O
brain O
damage O
by O
pilocarpine B
, O
though O
in O
the O
MK B
- I
801 I
- O
treated O
group O
, O
the O
pyramidal O
cells O
of O
hippocampus O
appeared O
darker O
than O
normal O
. O

In O
all O
treatments O
, O
granule O
cells O
of O
the O
dentate O
gyrus O
were O
not O
affected O
. O

4 O
. O

These O
results O
indicate O
that O
status O
epilepticus O
induced O
by O
pilocarpine B
is O
initiated O
by O
cholinergic O
overstimulation O
and O
propagated O
by O
glutamatergic O
transmission O
, O
the O
elevation O
of O
which O
may O
cause O
brain O
damage O
through O
an O
excitatory O
NMDA B
receptor O
- O
mediated O
mechanism O
. O

Paclitaxel B
, O
5 B
- I
fluorouracil I
, O
and O
folinic B
acid I
in O
metastatic O
breast O
cancer O
: O
BRE B
- I
26 I
, O
a O
phase O
II O
trial O
. O

5 B
- I
Fluorouracil I
plus O
folinic B
acid I
and O
paclitaxel B
( O
Taxol B
; O
Bristol O
- O
Myers O
Squibb O
Company O
, O
Princeton O
, O
NJ O
) O
are O
effective O
salvage O
therapies O
for O
metastatic O
breast O
cancer O
patients O
. O

Paclitaxel B
and O
5 B
- I
fluorouracil I
have O
additive O
cytotoxicity O
in O
MCF O
- O
7 O
cell O
lines O
. O

We O
performed O
a O
phase O
II O
trial O
of O
paclitaxel B
175 O
mg O
/ O
m2 O
over O
3 O
hours O
on O
day O
I O
followed O
by O
folinic B
acid I
300 O
mg O
over O
1 O
hour O
before O
5 B
- I
fluorouracil I
350 O
mg O
/ O
m2 O
on O
days O
1 O
to O
3 O
every O
28 O
days O
( O
TFL O
) O
in O
women O
with O
metastatic O
breast O
cancer O
. O

Analysis O
is O
reported O
on O
37 O
patients O
with O
a O
minimum O
of O
6 O
months O
follow O
- O
up O
who O
received O
a O
total O
of O
192 O
cycles O
of O
TFL B
: O
nine O
cycles O
( O
5 O
% O
) O
were O
associated O
with O
grade O
3 O
/ O
4 O
neutropenia O
requiring O
hospitalization O
; O
seven O
( O
4 O
% O
) O
cycles O
in O
two O
patients O
required O
granulocyte O
colony O
- O
stimulating O
factor O
due O
to O
neutropenia O
; O
no O
patient O
required O
platelet O
transfusions O
. O

Grade O
3 O
/ O
4 O
nonhematologic O
toxicities O
were O
uncommon O
. O

Among O
the O
34 O
patients O
evaluable O
for O
response O
, O
there O
were O
three O
complete O
responses O
( O
9 O
% O
) O
and O
18 O
partial O
responses O
( O
53 O
% O
) O
for O
an O
overall O
response O
rate O
of O
62 O
% O
. O

Of O
the O
19 O
evaluable O
patients O
with O
prior O
doxorubicin B
exposure O
, O
11 O
( O
58 O
% O
) O
responded O
compared O
with O
nine O
of O
15 O
( O
60 O
% O
) O
without O
prior O
doxorubicin B
. O

Plasma O
paclitaxel B
concentrations O
were O
measured O
at O
the O
completion O
of O
paclitaxel B
infusion O
and O
at O
24 O
hours O
in O
19 O
patients O
. O

TFL B
is O
an O
active O
, O
well O
- O
tolerated O
regimen O
in O
metastatic O
breast O
cancer O
. O

Efficacy O
and O
proarrhythmia O
with O
the O
use O
of O
d B
, I
l I
- I
sotalol I
for O
sustained O
ventricular O
tachyarrhythmias O
. O

This O
study O
prospectively O
evaluated O
the O
clinical O
efficacy O
, O
the O
incidence O
of O
torsades O
de O
pointes O
, O
and O
the O
presumable O
risk O
factors O
for O
torsades O
de O
pointes O
in O
patients O
treated O
with O
d B
, I
l I
- I
sotalol I
for O
sustained O
ventricular O
tachyarrhythmias O
. O

Eighty O
- O
one O
consecutive O
patients O
( O
54 O
with O
coronary O
artery O
disease O
, O
and O
20 O
with O
dilated O
cardiomyopathy O
) O
with O
inducible O
sustained O
ventricular O
tachycardia O
or O
ventricular O
fibrillation O
received O
oral O
d B
, I
l I
- I
sotalol I
to O
prevent O
induction O
of O
the O
ventricular O
tachyarrhythmia O
. O

During O
oral O
loading O
with O
d B
, I
l I
- I
sotalol I
, O
continuous O
electrocardiographic O
( O
ECG O
) O
monitoring O
was O
performed O
. O

Those O
patients O
in O
whom O
d B
, I
l I
- I
sotalol I
prevented O
induction O
of O
ventricular O
tachycardia O
or O
ventricular O
fibrillation O
were O
discharged O
with O
the O
drug O
and O
followed O
up O
on O
an O
outpatient O
basis O
for O
21 O
+ O
/ O
- O
18 O
months O
. O

Induction O
of O
the O
ventricular O
tachyarrhythmia O
was O
prevented O
by O
oral O
d B
, I
l I
- I
sotalol I
in O
35 O
( O
43 O
% O
) O
patients O
; O
the O
ventricular O
tachyarrhythmia O
remained O
inducible O
in O
40 O
( O
49 O
% O
) O
patients O
; O
and O
two O
( O
2 O
. O
5 O
% O
) O
patients O
did O
not O
tolerate O
even O
40 O
mg O
of O
d B
, I
l I
- I
sotalol I
once O
daily O
. O

Four O
( O
5 O
% O
) O
patients O
had O
from O
torsades O
de O
pointes O
during O
the O
initial O
oral O
treatment O
with O
d B
, I
l I
- I
sotalol I
. O

Neither O
ECG O
[ O
sinus O
- O
cycle O
length O
( O
SCL O
) O
, O
QT O
or O
QTc O
interval O
, O
or O
U O
wave O
] O
nor O
clinical O
parameters O
identified O
patients O
at O
risk O
for O
torsades O
de O
pointes O
. O

However O
, O
the O
oral O
dose O
of O
d B
, I
l I
- I
sotalol I
was O
significantly O
lower O
in O
patients O
with O
torsades O
de O
pointes O
( O
200 O
+ O
/ O
- O
46 O
vs O
. O
328 O
+ O
/ O
- O
53 O
mg O
/ O
day O
; O
p O
= O
0 O
. O
0017 O
) O
. O

Risk O
factors O
associated O
with O
the O
development O
of O
torsades O
de O
pointes O
were O
the O
appearance O
of O
an O
U O
wave O
( O
p O
= O
0 O
. O
049 O
) O
, O
female O
gender O
( O
p O
= O
0 O
. O
015 O
) O
, O
and O
significant O
dose O
- O
corrected O
changes O
of O
SCL O
, O
QT O
interval O
, O
and O
QTc O
interval O
( O
p O
< O
0 O
. O
05 O
) O
. O

During O
follow O
- O
up O
, O
seven O
( O
20 O
% O
) O
patients O
had O
a O
nonfatal O
ventricular O
tachycardia O
recurrence O
, O
and O
two O
( O
6 O
% O
) O
patients O
died O
suddenly O
. O

One O
female O
patient O
with O
stable O
cardiac O
disease O
had O
recurrent O
torsades O
de O
pointes O
after O
2 O
years O
of O
successful O
treatment O
with O
d B
, I
l I
- I
sotalol I
. O

Torsades O
de O
pointes O
occurred O
early O
during O
treatment O
even O
with O
low O
doses O
of O
oral O
d B
, I
l I
- I
sotalol I
. O

Pronounced O
changes O
in O
the O
surface O
ECG O
( O
cycle O
length O
, O
QT O
, O
and O
QTc O
) O
in O
relation O
to O
the O
dose O
of O
oral O
d B
, I
l I
- I
sotalol I
might O
identify O
a O
subgroup O
of O
patients O
with O
an O
increased O
risk O
for O
torsades O
de O
pointes O
. O

Other O
ECG O
parameters O
before O
the O
application O
of O
d B
, I
l I
- I
sotalol I
did O
not O
identify O
patients O
at O
increased O
risk O
for O
torsades O
de O
pointes O
. O

Recurrence O
rates O
of O
ventricular O
tachyarrhythmias O
are O
high O
despite O
complete O
suppression O
of O
the O
arrhythmia O
during O
programmed O
stimulation O
. O

Therefore O
programmed O
electrical O
stimulation O
in O
the O
case O
of O
d B
, I
l I
- I
sotalol I
seems O
to O
be O
of O
limited O
prognostic O
value O
. O

Chronic O
hyperprolactinemia O
and O
changes O
in O
dopamine B
neurons O
. O

The O
tuberoinfundibular O
dopaminergic O
( O
TIDA O
) O
system O
is O
known O
to O
inhibit O
prolactin O
( O
PRL O
) O
secretion O
. O

In O
young O
animals O
this O
system O
responds O
to O
acute O
elevations O
in O
serum O
PRL O
by O
increasing O
its O
activity O
. O

However O
, O
this O
responsiveness O
is O
lost O
in O
aging O
rats O
with O
chronically O
high O
serum O
PRL O
levels O
. O

The O
purpose O
of O
this O
study O
was O
to O
induce O
hyperprolactinemia O
in O
rats O
for O
extended O
periods O
of O
time O
and O
examine O
its O
effects O
on O
dopaminergic O
systems O
in O
the O
brain O
. O

Hyperprolactinemia O
was O
induced O
by O
treatment O
with O
haloperidol B
, O
a O
dopamine B
receptor O
antagonist O
, O
and O
Palkovits O
' O
microdissection O
technique O
in O
combination O
with O
high O
- O
performance O
liquid O
chromatography O
was O
used O
to O
measure O
neurotransmitter O
concentrations O
in O
several O
areas O
of O
the O
brain O
. O

After O
6 O
months O
of O
hyperprolactinemia O
, O
dopamine B
( O
DA B
) O
concentrations O
in O
the O
median O
eminence O
( O
ME O
) O
increased O
by O
84 O
% O
over O
the O
control O
group O
. O

Nine O
months O
of O
hyperprolactinemia O
produced O
a O
50 O
% O
increase O
in O
DA B
concentrations O
in O
the O
ME O
over O
the O
control O
group O
. O

However O
, O
DA B
response O
was O
lost O
if O
a O
9 O
- O
month O
long O
haloperidol B
- O
induced O
hyperprolactinemia O
was O
followed O
by O
a O
1 O
1 O
/ O
2 O
month O
- O
long O
extremely O
high O
increase O
in O
serum O
PRL O
levels O
produced O
by O
implantation O
of O
MMQ O
cells O
under O
the O
kidney O
capsule O
. O

There O
was O
no O
change O
in O
the O
levels O
of O
DA B
, O
norepinephrine B
( O
NE B
) O
, O
serotonin B
( O
5 B
- I
HT I
) O
, O
or O
their O
metabolites O
in O
the O
arcuate O
nucleus O
( O
AN O
) O
, O
medial O
preoptic O
area O
( O
MPA O
) O
, O
caudate O
putamen O
( O
CP O
) O
, O
substantia O
nigra O
( O
SN O
) O
, O
and O
zona O
incerta O
( O
ZI O
) O
, O
except O
for O
a O
decrease O
in O
5 B
- I
hydroxyindoleacetic I
acid I
( O
5 B
- I
HIAA I
) O
in O
the O
AN O
after O
6 O
- O
months O
of O
hyperprolactinemia O
and O
an O
increase O

in O
DA B
concentrations O
in O
the O
AN O
after O
9 O
- O
months O
of O
hyperprolactinemia O
. O

These O
results O
demonstrate O
that O
hyperprolactinemia O
specifically O
affects O
TIDA O
neurons O
and O
these O
effects O
vary O
, O
depending O
on O
the O
duration O
and O
intensity O
of O
hyperprolactinemia O
. O

The O
age O
- O
related O
decrease O
in O
hypothalamic O
dopamine B
function O
may O
be O
associated O
with O
increases O
in O
PRL O
secretion O
. O

Treatment O
- O
related O
disseminated O
necrotizing O
leukoencephalopathy O
with O
characteristic O
contrast O
enhancement O
of O
the O
white O
matter O
. O

This O
report O
describes O
unique O
contrast O
enhancement O
of O
the O
white O
matter O
on O
T1 O
- O
weighted O
magnetic O
resonance O
images O
of O
two O
patients O
with O
disseminated O
necrotizing O
leukoencephalopathy O
, O
which O
developed O
from O
acute O
lymphoblastic O
leukemia O
treated O
with O
high O
- O
dose O
methotrexate B
. O

In O
both O
patients O
, O
the O
enhancement O
was O
more O
pronounced O
near O
the O
base O
of O
the O
brain O
than O
at O
the O
vertex O
. O

Necropsy O
of O
the O
first O
case O
revealed O
loss O
of O
myelination O
and O
necrosis O
of O
the O
white O
matter O
. O

Possible O
mechanisms O
causing O
such O
a O
leukoencephalopathy O
are O
discussed O
. O

Thrombotic O
complications O
in O
acute O
promyelocytic O
leukemia O
during O
all B
- I
trans I
- I
retinoic I
acid I
therapy O
. O

A O
case O
of O
acute O
renal O
failure O
, O
due O
to O
occlusion O
of O
renal O
vessels O
in O
a O
patient O
with O
acute O
promyelocytic O
leukemia O
( O
APL O
) O
treated O
with O
all B
- I
trans I
- I
retinoic I
acid I
( O
ATRA B
) O
and O
tranexamic B
acid I
has O
been O
described O
recently O
. O

We O
report O
a O
case O
of O
acute O
renal O
failure O
in O
an O
APL O
patient O
treated O
with O
ATRA B
alone O
. O

This O
case O
further O
supports O
the O
concern O
about O
thromboembolic O
complications O
associated O
with O
ATRA B
therapy O
in O
APL O
patients O
. O

The O
patients O
, O
a O
43 O
- O
year O
- O
old O
man O
, O
presented O
all O
the O
signs O
and O
symptoms O
of O
APL O
and O
was O
included O
in O
a O
treatment O
protocol O
with O
ATRA B
. O

After O
10 O
days O
of O
treatment O
, O
he O
developed O
acute O
renal O
failure O
that O
was O
completely O
reversible O
after O
complete O
remission O
of O
APL O
was O
achieved O
and O
therapy O
discontinued O
. O

We O
conclude O
that O
ATRA B
is O
a O
valid O
therapeutic O
choice O
for O
patients O
with O
APL O
, O
although O
the O
procoagulant O
tendency O
is O
not O
completely O
corrected O
. O

Thrombotic O
events O
, O
however O
, O
could O
be O
avoided O
by O
using O
low O
- O
dose O
heparin B
. O

Pupillary O
changes O
associated O
with O
the O
development O
of O
stimulant O
- O
induced O
mania O
: O
a O
case O
report O
. O

A O
30 O
- O
year O
- O
old O
cocaine B
- O
dependent O
man O
who O
was O
a O
subject O
in O
a O
study O
evaluating O
the O
anticraving O
efficacy O
of O
the O
stimulant O
medication O
diethylpropion B
( O
DEP B
) O
became O
manic O
during O
his O
second O
week O
on O
the O
study O
drug O
. O

Pupillometric O
changes O
while O
on O
DEP O
, O
especially O
changes O
in O
the O
total O
power O
of O
pupillary O
oscillation O
, O
were O
dramatically O
different O
than O
those O
observed O
in O
the O
eight O
other O
study O
subjects O
who O
did O
not O
become O
manic O
. O

The O
large O
changes O
in O
total O
power O
of O
pupillary O
oscillation O
occurred O
a O
few O
days O
before O
the O
patient O
became O
fully O
manic O
. O

Such O
medication O
- O
associated O
changes O
in O
the O
total O
power O
of O
pupillary O
oscillation O
might O
be O
of O
utility O
in O
identifying O
persons O
at O
risk O
for O
manic O
- O
like O
adverse O
effects O
during O
the O
medical O
use O
of O
psychomotor O
stimulants O
or O
sympathomimetic O
agents O
. O

Fetal O
risks O
due O
to O
warfarin B
therapy O
during O
pregnancy O
. O

Two O
mothers O
with O
heart O
valve O
prosthesis O
were O
treated O
with O
warfarin B
during O
pregnancy O
. O

In O
the O
first O
case O
a O
caesarean O
section O
was O
done O
one O
week O
after O
replacement O
of O
warfarin B
with O
heparin B
. O

The O
baby O
died O
of O
cerebral O
and O
pulmonary O
hemorrhage O
. O

The O
second O
mother O
had O
a O
male O
infant O
by O
caesarean O
section O
. O

The O
baby O
showed O
warfarin B
- O
induced O
embryopathy O
with O
nasal O
hypoplasia O
and O
stippled O
epiphyses O
( O
chondrodysplasia O
punctata O
) O
. O

Nasal O
hypoplasia O
with O
or O
without O
stippled O
epiphyses O
has O
now O
been O
reported O
in O
11 O
infants O
born O
to O
mothers O
treated O
with O
warfarin B
during O
the O
first O
trimester O
, O
and O
a O
causal O
association O
is O
probable O
. O

In O
view O
of O
the O
risks O
to O
both O
mother O
and O
fetus O
in O
women O
with O
prosthetic O
cardiac O
valves O
it O
is O
recommended O
that O
therapeutic O
abortion O
be O
advised O
as O
the O
first O
alternative O
. O

The O
negative O
mucosal O
potential O
: O
separating O
central O
and O
peripheral O
effects O
of O
NSAIDs O
in O
man O
. O

OBJECTIVE O
: O
We O
wanted O
to O
test O
whether O
assessment O
of O
both O
a O
central O
pain O
- O
related O
signal O
( O
chemo O
- O
somatosensory O
evoked O
potential O
, O
CSSEP O
) O
and O
a O
concomitantly O
recorded O
peripheral O
signal O
( O
negative O
mucosal O
potential O
, O
NMP O
) O
allows O
for O
separation O
of O
central O
and O
peripheral O
effects O
of O
NSAIDs O
. O

For O
this O
purpose O
, O
experimental O
conditions O
were O
created O
in O
which O
NSAIDs O
had O
previously O
been O
observed O
to O
produce O
effects O
on O
phasic O
and O
tonic O
pain O
by O
either O
central O
or O
peripheral O
mechanisms O
. O

METHODS O
: O
According O
to O
a O
double O
- O
blind O
, O
randomised O
, O
controlled O
, O
threefold O
cross O
- O
over O
design O
, O
18 O
healthy O
subjects O
( O
11 O
males O
, O
7 O
females O
; O
mean O
age O
26 O
years O
) O
received O
either O
placebo O
, O
400 O
mg O
ibuprofen B
, O
or O
800 O
mg O
ibuprofen B
. O

Phasic O
pain O
was O
applied O
by O
means O
of O
short O
pulses O
of O
CO2 B
to O
the O
nasal O
mucosa O
( O
stimulus O
duration O
500 O
ms O
, O
interval O
approximately O
60 O
s O
) O
, O
and O
tonic O
pain O
was O
induced O
in O
the O
nasal O
cavity O
by O
means O
of O
dry O
air O
of O
controlled O
temperature O
, O
humidity O
and O
flow O
rate O
( O
22 O
degrees O
C O
, O
0 O
% O
relative O
humidity O
, O
145 O
ml O
. O
s O
- O
1 O
) O
. O

Both O
CSSEPs O
as O
central O
and O
NMPs O
as O
peripheral O
correlates O
of O
pain O
were O
obtained O
in O
response O
to O
the O
CO2 B
stimuli O
. O

Additionally O
, O
the O
subjects O
rated O
the O
intensity O
of O
both O
phasic O
and O
tonic O
pain O
by O
means O
of O
visual O
analogue O
scales O
. O

RESULTS O
: O
As O
described O
earlier O
, O
administration O
of O
ibuprofen B
was O
followed O
by O
a O
decrease O
in O
tonic O
pain O
but O
- O
relative O
to O
placebo O
- O
an O
increase O
in O
correlates O
of O
phasic O
pain O
, O
indicating O
a O
specific O
effect O
of O
ibuprofen B
on O
the O
interaction O
between O
the O
pain O
stimuli O
under O
these O
special O
experimental O
conditions O
. O

Based O
on O
the O
similar O
behaviour O
of O
CSSEP O
and O
NMP O
, O
it O
was O
concluded O
that O
the O
pharmacological O
process O
underlying O
this O
phenomenon O
was O
localised O
in O
the O
periphery O
. O

By O
means O
of O
the O
simultaneous O
recording O
of O
interrelated O
peripheral O
and O
central O
electrophysiologic O
correlates O
of O
nociception O
, O
it O
was O
possible O
to O
separate O
central O
and O
peripheral O
effects O
of O
an O
NSAID O
. O

The O
major O
advantage O
of O
this O
pain O
model O
is O
the O
possibility O
of O
obtaining O
peripheral O
pain O
- O
related O
activity O
directly O
using O
a O
non O
- O
invasive O
technique O
in O
humans O
. O

Effect O
of O
D B
- I
Glucarates I
on O
basic O
antibiotic O
- O
induced O
renal O
damage O
in O
rats O
. O

Dehydrated O
rats O
regularly O
develop O
acute O
renal O
failure O
following O
single O
injection O
of O
aminoglycoside B
antibiotics O
combined O
with O
dextran B
or O
of O
antibiotics O
only O
. O

Oral O
administration O
of O
2 B
, I
5 I
- I
di I
- I
O I
- I
acetyl I
- I
D I
- I
glucaro I
- I
1 I
, I
4 I
- I
6 I
, I
3 I
- I
dilactone I
protected O
rats O
against O
renal O
failure O
induced O
by O
kanamycin B
- O
dextran B
. O

The O
protective O
effect O
was O
prevalent O
among O
D B
- I
glucarates I
, O
and O
also O
to O
other O
saccharic B
acid I
, O
hexauronic B
acids I
and O
hexaaldonic B
acids I
, O
although O
to O
a O
lesser O
degree O
, O
but O
not O
to O
a O
hexaaldose B
, O
sugar B
alcohols I
, O
substances O
inthe O
TCA O
cycle O
and O
other O
acidic O
compounds O
. O

D B
- I
Glucarates I
were O
effective O
against O
renal O
damage O
induced O
by O
peptide O
antibiotics O
as O
well O
as O
various O
aminoglycoside B
antibitocis O
. O

Dose O
- O
responses O
were O
observed O
in O
the O
protective O
effect O
of O
D B
- I
Glucarates I
. O

With O
a O
D B
- I
glucarate I
of O
a O
fixed O
size O
of O
dose O
, O
approximately O
the O
same O
degree O
of O
protection O
was O
obtained O
against O
renal O
damages O
induced O
by O
different O
basic O
antibiotics O
despite O
large O
disparities O
in O
administration O
doses O
of O
different O
antibiotics O
. O

D B
- I
Glucarates I
had O
the O
ability O
to O
prevent O
renal O
damage O
but O
not O
to O
cure O
it O
. O

Rats O
excreted O
acidic O
urine O
when O
they O
were O
spared O
from O
renal O
lesions O
by O
monosaccharides B
. O

The O
reduction O
effect O
of O
D B
- I
glucarates I
against O
nephrotoxicity O
of O
basic O
antibiotics O
was O
discussed O
. O

Acute O
severe O
depression O
following O
peri O
- O
operative O
ondansetron B
. O

A O
41 O
- O
year O
- O
old O
woman O
with O
a O
strong O
history O
of O
postoperative O
nausea O
and O
vomiting O
presented O
for O
abdominal O
hysterectomy O
3 O
months O
after O
a O
previous O
anaesthetic O
where O
ondansetron B
prophylaxis O
had O
been O
used O
. O

She O
had O
developed O
a O
severe O
acute O
major O
depression O
disorder O
almost O
immediately O
thereafter O
, O
possibly O
related O
to O
the O
use O
of O
a O
serotonin B
antagonist O
. O

Nine O
years O
before O
she O
had O
experienced O
a O
self O
- O
limited O
puerperal O
depressive O
episode O
. O

Anaesthesia O
with O
a O
propofol B
infusion O
and O
avoidance O
of O
serotonin B
antagonists O
provided O
a O
nausea O
- O
free O
postoperative O
course O
without O
exacerbation O
of O
the O
depression O
disorder O
. O

Hypertensive O
response O
during O
dobutamine B
stress O
echocardiography O
. O

Among O
3 O
, O
129 O
dobutamine B
stress O
echocardiographic O
studies O
, O
a O
hypertensive O
response O
, O
defined O
as O
systolic O
blood O
pressure O
( O
BP O
) O
> O
or O
= O
220 O
mm O
Hg O
and O
/ O
or O
diastolic O
BP O
> O
or O
= O
110 O
mm O
Hg O
, O
occurred O
in O
30 O
patients O
( O
1 O
% O
) O
. O

Patients O
with O
this O
response O
more O
often O
had O
a O
history O
of O
hypertension O
and O
had O
higher O
resting O
systolic O
and O
diastolic O
BP O
before O
dobutamine B
infusion O
. O

Continuously O
nebulized O
albuterol B
in O
severe O
exacerbations O
of O
asthma O
in O
adults O
: O
a O
case O
- O
controlled O
study O
. O

A O
retrospective O
, O
case O
- O
controlled O
analysis O
comparing O
patients O
admitted O
to O
a O
medical O
intensive O
care O
unit O
with O
severe O
exacerbations O
of O
asthma O
who O
received O
continuously O
nebulized O
albuterol B
( O
CNA O
) O
versus O
intermittent O
albuterol B
( O
INA B
) O
treatments O
is O
reported O
. O

Forty O
matched O
pairs O
of O
patients O
with O
asthma O
are O
compared O
. O

CNA B
was O
administered O
for O
a O
mean O
of O
11 O
+ O
/ O
- O
10 O
hr O
. O

The O
incidence O
of O
cardiac O
dysrhythmias O
was O
similar O
between O
groups O
. O

Symptomatic O
hypokalemia O
did O
not O
occur O
. O

CNA O
patients O
had O
higher O
heart O
rates O
during O
treatment O
, O
which O
may O
reflect O
severity O
of O
illness O
. O

The O
incidence O
of O
intubation O
was O
similar O
. O

We O
conclude O
that O
CNA B
and O
INA B
demonstrated O
similar O
profiles O
with O
regard O
to O
safety O
, O
morbidity O
, O
and O
mortality O
. O

Paraplegia O
following O
intrathecal O
methotrexate B
: O
report O
of O
a O
case O
and O
review O
of O
the O
literature O
. O

A O
patient O
who O
developed O
paraplegia O
following O
the O
intrathecal O
instillation O
of O
methotrexate B
is O
discribed O
. O

The O
ten O
previously O
reported O
cases O
of O
this O
unusual O
complication O
are O
reviewed O
. O

The O
following O
factors O
appear O
to O
predispose O
to O
the O
development O
of O
this O
complication O
: O
abnormal O
cerebrospinal O
dynamics O
related O
to O
the O
presence O
of O
central O
nervous O
system O
leukemia O
, O
and O
epidural O
cerebrospinal O
leakage O
; O
elevated O
cerebrospinal O
fluid O
methothexate B
concentration O
related O
to O
abnormal O
cerebrospinal O
fluid O
dynamics O
and O
to O
inappropriately O
high O
methotrexate B
doses O
based O
on O
body O
surface O
area O
calculations O
in O
older O
children O
and O
adults O
; O
the O
presence O
of O
neurotoxic O
preservatives O
in O
commercially O
available O
methotrexate B
preparations O
and O
diluents O
; O
and O
the O
use O
of O

methotrexate B
diluents O
of O
unphysiologic O
pH O
, O
ionic O
content O
and O
osmolarity O
. O

The O
role O
of O
methotrexate B
contaminants O
, O
local O
folate B
deficiency O
, O
and O
cranial O
irradiation O
in O
the O
pathogenesis O
of O
intrathecal O
methotrexate B
toxicity O
is O
unclear O
. O

The O
incidence O
of O
neurotoxicity O
may O
be O
reduced O
by O
employing O
lower O
doses O
of O
methotrexate B
in O
the O
presence O
of O
central O
nervous O
system O
leukemia O
, O
in O
older O
children O
and O
adults O
, O
and O
in O
the O
presence O
of O
epidural O
leakage O
. O

Only O
preservative O
- O
free O
methotrexate B
in O
Elliott O
' O
s O
B O
Solution O
at O
a O
concentration O
of O
not O
more O
than O
1 O
mg O
/ O
ml O
should O
be O
used O
for O
intrathecal O
administration O
. O

Periodic O
monitoring O
of O
cerebruspinal O
fluid O
methotrexate B
levels O
may O
be O
predictive O
of O
the O
development O
of O
serious O
neurotoxicity O
. O

Hyperosmolar O
nonketotic O
coma O
precipitated O
by O
lithium B
- O
induced O
nephrogenic O
diabetes O
insipidus O
. O

A O
45 O
- O
year O
- O
old O
man O
, O
with O
a O
10 O
- O
year O
history O
of O
manic O
depression O
treated O
with O
lithium B
, O
was O
admitted O
with O
hyperosmolar O
, O
nonketotic O
coma O
. O

He O
gave O
a O
five O
- O
year O
history O
of O
polyuria O
and O
polydipsia O
, O
during O
which O
time O
urinalysis O
had O
been O
negative O
for O
glucose B
. O

After O
recovery O
from O
hyperglycaemia O
, O
he O
remained O
polyuric O
despite O
normal O
blood O
glucose B
concentrations O
; O
water O
deprivation O
testing O
indicated O
nephrogenic O
diabetes O
insipidus O
, O
likely O
to O
be O
lithium B
- O
induced O
. O

We O
hypothesize O
that O
when O
this O
man O
developed O
type O
2 O
diabetes O
, O
chronic O
polyuria O
due O
to O
nephrogenic O
diabetes O
insipidus O
was O
sufficient O
to O
precipitate O
hyperosmolar O
dehydration O
. O

Effects O
of O
the O
intracoronary O
infusion O
of O
cocaine B
on O
left O
ventricular O
systolic O
and O
diastolic O
function O
in O
humans O
. O

BACKGROUND O
: O
In O
dogs O
, O
a O
large O
amount O
of O
intravenous O
cocaine B
causes O
a O
profound O
deterioration O
of O
left O
ventricular O
( O
LV O
) O
systolic O
function O
and O
an O
increase O
in O
LV O
end O
- O
diastolic O
pressure O
. O

This O
study O
was O
done O
to O
assess O
the O
influence O
of O
a O
high O
intracoronary O
cocaine B
concentration O
on O
LV O
systolic O
and O
diastolic O
function O
in O
humans O
. O

METHODS O
AND O
RESULTS O
: O
In O
20 O
patients O
( O
14 O
men O
and O
6 O
women O
aged O
39 O
to O
72 O
years O
) O
referred O
for O
cardiac O
catheterization O
for O
the O
evaluation O
of O
chest O
pain O
, O
we O
measured O
heart O
rate O
, O
systemic O
arterial O
pressure O
, O
LV O
pressure O
and O
its O
first O
derivative O
( O
dP O
/ O
dt O
) O
, O
and O
LV O
volumes O
and O
ejection O
fraction O
before O
and O
during O
the O
final O
2 O
to O
3 O
minutes O
of O
a O
15 O
- O
minute O
intracoronary O
infusion O
of O
saline O
( O
n O
= O
10 O
, O
control O
subjects O
) O
or O
cocaine B
hydrochloride I
1 O
mg O
/ O
min O
( O
n O
= O
10 O
) O
. O

No O
variable O
changed O
with O
saline O
. O

With O
cocaine B
, O
the O
drug O
concentration O
in O
blood O
obtained O
from O
the O
coronary O
sinus O
was O
3 O
. O
0 O
+ O
/ O
- O
0 O
. O
4 O
( O
mean O
+ O
/ O
- O
SD O
) O
mg O
/ O
L O
, O
similar O
in O
magnitude O
to O
the O
blood O
cocaine B
concentration O
reported O
in O
abusers O
dying O
of O
cocaine B
intoxication O
. O

Cocaine B
induced O
no O
significant O
change O
in O
heart O
rate O
, O
LV O
dP O
/ O
dt O
( O
positive O
or O
negative O
) O
, O
or O
LV O
end O
- O
diastolic O
volume O
, O
but O
it O
caused O
an O
increase O
in O
systolic O
and O
mean O
arterial O
pressures O
, O
LV O
end O
- O
diastolic O
pressure O
, O
and O
LV O
end O
- O
systolic O
volume O
, O
as O
well O
as O
a O
decrease O
in O
LV O
ejection O
fraction O
. O

CONCLUSIONS O
: O
In O
humans O
, O
the O
intracoronary O
infusion O
of O
cocaine B
sufficient O
in O
amount O
to O
achieve O
a O
high O
drug O
concentration O
in O
coronary O
sinus O
blood O
causes O
a O
deterioration O
of O
LV O
systolic O
and O
diastolic O
performance O
. O

Ascending O
dose O
tolerance O
study O
of O
intramuscular O
carbetocin B
administered O
after O
normal O
vaginal O
birth O
. O

OBJECTIVE O
: O
To O
determine O
the O
maximum O
tolerated O
dose O
( O
MTD O
) O
of O
carbetocin B
( O
a O
long O
- O
acting O
synthetic O
analogue O
of O
oxytocin B
) O
, O
when O
administered O
immediately O
after O
vaginal O
delivery O
at O
term O
. O

MATERIALS O
AND O
METHODS O
: O
Carbetocin B
was O
given O
as O
an O
intramuscular O
injection O
immediately O
after O
the O
birth O
of O
the O
infant O
in O
45 O
healthy O
women O
with O
normal O
singleton O
pregnancies O
who O
delivered O
vaginally O
at O
term O
. O

Dosage O
groups O
of O
15 O
, O
30 O
, O
50 O
, O
75 O
, O
100 O
, O
125 O
, O
150 O
, O
175 O
or O
200 O
microg O
carbetocin B
were O
assigned O
to O
blocks O
of O
three O
women O
according O
to O
the O
continual O
reassessment O
method O
( O
CRM O
) O
. O

RESULTS O
: O
All O
dosage O
groups O
consisted O
of O
three O
women O
, O
except O
those O
with O
100 O
microg O
( O
n O
= O
6 O
) O
and O
200 O
microg O
( O
n O
= O
18 O
) O
. O

Recorded O
were O
dose O
- O
limiting O
adverse O
events O
: O
hyper O
- O
or O
hypotension O
( O
three O
) O
, O
severe O
abdominal O
pain O
( O
0 O
) O
, O
vomiting O
( O
0 O
) O
and O
retained O
placenta O
( O
four O
) O
. O

Serious O
adverse O
events O
occurred O
in O
seven O
women O
: O
six O
cases O
with O
blood O
loss O
> O
or O
= O
1000 O
ml O
, O
four O
cases O
of O
manual O
placenta O
removal O
, O
five O
cases O
of O
additional O
oxytocics O
administration O
and O
five O
cases O
of O
blood O
transfusion O
. O

Maximum O
blood O
loss O
was O
greatest O
at O
the O
upper O
and O
lower O
dose O
levels O
, O
and O
lowest O
in O
the O
70 O
- O
125 O
microg O
dose O
range O
. O

Four O
out O
of O
six O
cases O
with O
blood O
loss O
> O
or O
= O
1000 O
ml O
occurred O
in O
the O
200 O
microg O
group O
. O

The O
majority O
of O
additional O
administration O
of O
oxytocics O
( O
4 O
/ O
5 O
) O
and O
blood O
transfusion O
( O
3 O
/ O
5 O
) O
occurred O
in O
the O
dose O
groups O
of O
200 O
microg O
. O

All O
retained O
placentae O
were O
found O
in O
the O
group O
of O
200 O
microg O
. O

CONCLUSION O
: O
The O
MTD O
was O
calculated O
to O
be O
at O
200 O
microg O
carbetocin B
. O

Heparin B
- O
induced O
thrombocytopenia O
, O
paradoxical O
thromboembolism O
, O
and O
other O
side O
effects O
of O
heparin B
therapy O
. O

Although O
several O
new O
anticoagulant O
drugs O
are O
in O
development O
, O
heparin B
remains O
the O
drug O
of O
choice O
for O
most O
anticoagulation O
needs O
. O

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

Important O
untoward O
effects O
of O
heparin B
therapy O
including O
heparin B
- O
induced O
thrombocytopenia O
, O
heparin B
- O
associated O
osteoporosis O
, O
eosinophilia O
, O
skin O
reactions O
, O
allergic O
reactions O
other O
than O
thrombocytopenia O
and O
alopecia O
will O
be O
discussed O
in O
this O
article O
. O

Nonopaque O
crystal O
deposition O
causing O
ureteric O
obstruction O
in O
patients O
with O
HIV O
undergoing O
indinavir B
therapy O
. O

OBJECTIVE O
: O
We O
describe O
the O
unique O
CT O
features O
of O
ureteric O
calculi O
in O
six O
HIV O
- O
infected O
patients O
receiving O
indinavir B
, O
the O
most O
commonly O
used O
HIV O
protease O
inhibitor O
, O
which O
is O
associated O
with O
an O
increased O
incidence O
of O
urolithiasis O
. O

CONCLUSION O
: O
Ureteric O
obstruction O
caused O
by O
precipitated O
indinavir B
crystals O
may O
be O
difficult O
to O
diagnose O
with O
unenhanced O
CT O
. O

The O
calculi O
are O
not O
opaque O
, O
and O
secondary O
signs O
of O
obstruction O
may O
be O
absent O
or O
minimal O
and O
should O
be O
sought O
carefully O
. O

Images O
may O
need O
to O
be O
obtained O
using O
i O
. O
v O
. O
contrast O
material O
to O
enable O
diagnosis O
of O
ureteric O
stones O
or O
obstruction O
in O
patients O
with O
HIV O
infection O
who O
receive O
indinavir B
therapy O
. O

Ischemic O
colitis O
and O
sumatriptan B
use O
. O

Sumatriptan B
succinate I
, O
a O
serotonin B
- O
1 O
( O
5 B
- I
hydroxytryptamine I
- O
1 O
) O
receptor O
agonist O
, O
is O
an O
antimigraine O
drug O
that O
is O
reported O
to O
act O
by O
selectively O
constricting O
intracranial O
arteries O
. O

Recently O
, O
vasopressor O
responses O
that O
are O
distinct O
from O
the O
cranial O
circulation O
have O
been O
demonstrated O
to O
occur O
in O
the O
systemic O
, O
pulmonary O
, O
and O
coronary O
circulations O
. O

Cases O
have O
been O
published O
of O
coronary O
vasospasm O
, O
myocardial O
ischemia O
, O
and O
myocardial O
infarction O
occurring O
after O
sumatriptan B
use O
. O

We O
report O
on O
the O
development O
of O
8 O
serious O
cases O
of O
ischemic O
colitis O
in O
patients O
with O
migraine O
treated O
with O
sumatriptan B
. O

Pallidotomy O
with O
the O
gamma O
knife O
: O
a O
positive O
experience O
. O

51 O
patients O
with O
medically O
refractory O
Parkinson O
' O
s O
disease O
underwent O
stereotactic O
posteromedial O
pallidotomy O
between O
August O
1993 O
and O
February O
1997 O
for O
treatment O
of O
bradykinesia O
, O
rigidity O
, O
and O
L B
- I
DOPA I
- O
induced O
dyskinesias O
. O

In O
29 O
patients O
, O
the O
pallidotomies O
were O
performed O
with O
the O
Leksell O
Gamma O
Knife O
and O
in O
22 O
they O
were O
performed O
with O
the O
standard O
radiofrequency O
( O
RF O
) O
method O
. O

Clinical O
assessment O
as O
well O
as O
blinded O
ratings O
of O
Unified O
Parkinson O
' O
s O
Disease O
Rating O
Scale O
( O
UPDRS O
) O
scores O
were O
carried O
out O
pre O
- O
and O
postoperatively O
. O

Mean O
follow O
- O
up O
time O
is O
20 O
. O
6 O
months O
( O
range O
6 O
- O
48 O
) O
and O
all O
except O
4 O
patients O
have O
been O
followed O
more O
than O
one O
year O
. O

85 O
percent O
of O
patients O
with O
dyskinesias O
were O
relieved O
of O
symptoms O
, O
regardless O
of O
whether O
the O
pallidotomies O
were O
performed O
with O
the O
Gamma O
Knife O
or O
radiofrequency O
methods O
. O

About O
2 O
/ O
3 O
of O
the O
patients O
in O
both O
Gamma O
Knife O
and O
radiofrequency O
groups O
showed O
improvements O
in O
bradykinesia O
and O
rigidity O
, O
although O
when O
considered O
as O
a O
group O
neither O
the O
Gamma O
Knife O
nor O
the O
radiofrequency O
group O
showed O
statistically O
significant O
improvements O
in O
UPDRS O
scores O
. O

One O
patient O
in O
the O
Gamma O
Knife O
group O
( O
3 O
. O
4 O
% O
) O
developed O
a O
homonymous O
hemianopsia O
9 O
months O
following O
treatment O
and O
5 O
patients O
( O
27 O
. O
7 O
% O
) O
in O
the O
radiofrequency O
group O
became O
transiently O
confused O
postoperatively O
. O

No O
other O
complications O
were O
seen O
. O

Gamma O
Knife O
pallidotomy O
is O
as O
effective O
as O
radiofrequency O
pallidotomy O
in O
controlling O
certain O
of O
the O
symptoms O
of O
Parkinson O
' O
s O
disease O
. O

It O
may O
be O
the O
only O
practical O
technique O
available O
in O
certain O
patients O
, O
such O
as O
those O
who O
take O
anticoagulants O
, O
have O
bleeding O
diatheses O
or O
serious O
systemic O
medical O
illnesses O
. O

It O
is O
a O
viable O
option O
for O
other O
patients O
as O
well O
. O

Centrally O
mediated O
cardiovascular O
effects O
of O
intracisternal O
application O
of O
carbachol B
in O
anesthetized O
rats O
. O

The O
pressor O
response O
to O
the O
intracisternal O
( O
i O
. O
c O
. O
) O
injection O
of O
carbachol B
( O
1 O
mug O
) O
in O
anesthetized O
rats O
was O
analyzed O
. O

This O
response O
was O
significantly O
reduced O
by O
the O
intravenous O
( O
i O
. O
v O
. O
) O
injection O
of O
guanethidine B
( O
5 O
mg O
) O
, O
hexamethonium B
( O
10 O
mg O
) O
or O
phentolamine B
( O
5 O
mg O
) O
, O
and O
conversely O
, O
potentiated O
by O
i O
. O
v O
. O
desmethylimipramine B
( O
0 O
. O
3 O
mg O
) O
, O
while O
propranolol B
( O
0 O
. O
5 O
mg O
) O
i O
. O
v O
. O
selectively O
inhibited O
the O
enlargement O
of O
pulse O
pressure O
and O
the O
tachycardia O
following O
i O
. O
c O
. O
carbachol B
( O
1 O
mug O
) O
. O

On O
the O
other O
hand O
, O
the O
pressor O
response O
to O
i O
. O
c O
. O
carbachol B
( O
1 O
mug O
) O
was O
almost O
completely O
blocked O
by O
i O
. O
c O
. O
atropine B
( O
3 O
mug O
) O
or O
hexamethonium B
( O
500 O
mug O
) O
, O
and O
significantly O
reduced O
by O
i O
. O
c O
. O
chlorpromazine B
( O
50 O
mug O
) O
but O
significantly O
potentiated O
by O
i O
. O
c O
. O
desmethylimipramine B
( O
30 O
mug O
) O
. O

The O
pressor O
response O
to O
i O
. O
c O
. O
carbachol B
( O
1 O
mug O
) O
remained O
unchanged O
after O
sectioning O
of O
the O
bilateral O
cervical O
vagal O
nerves O
but O
disappeared O
after O
sectioning O
of O
the O
spinal O
cord O
( O
C7 O
- O
C8 O
) O
. O

From O
the O
above O
result O
it O
is O
suggested O
that O
the O
pressor O
response O
to O
i O
. O
c O
. O
carbachol B
ortral O
and O
peripheral O
adrenergic O
mechanisms O
, O
and O
that O
the O
sympathetic O
trunk O
is O
the O
main O
pathway O
. O

Neuroleptic O
malignant O
syndrome O
and O
methylphenidate B
. O

A O
1 O
- O
year O
- O
old O
female O
presented O
with O
neuroleptic O
malignant O
syndrome O
probably O
caused O
by O
methylphenidate B
. O

She O
had O
defects O
in O
the O
supratentorial O
brain O
including O
the O
basal O
ganglia O
and O
the O
striatum O
( O
multicystic O
encephalomalacia O
) O
due O
to O
severe O
perinatal O
hypoxic O
- O
ischemic O
encephalopathy O
, O
which O
was O
considered O
to O
be O
a O
possible O
predisposing O
factor O
causing O
neuroleptic O
malignant O
syndrome O
. O

A O
dopaminergic O
blockade O
mechanism O
generally O
is O
accepted O
as O
the O
pathogenesis O
of O
this O
syndrome O
. O

However O
, O
methylphenidate B
is O
a O
dopamine B
agonist O
via O
the O
inhibition O
of O
uptake O
of O
dopamine B
, O
and O
therefore O
dopaminergic O
systems O
in O
the O
brainstem O
( O
mainly O
the O
midbrain O
) O
and O
the O
spinal O
cord O
were O
unlikely O
to O
participate O
in O
the O
onset O
of O
this O
syndrome O
. O

A O
relative O
gamma B
- I
aminobutyric I
acid I
- O
ergic O
deficiency O
might O
occur O
because O
diazepam B
, O
a O
gamma B
- I
aminobutyric I
acid I
- O
mimetic O
agent O
, O
was O
strikingly O
effective O
. O

This O
is O
the O
first O
reported O
patient O
with O
neuroleptic O
malignant O
syndrome O
probably O
caused O
by O
methylphenidate B
. O

Differential O
effects O
of O
17alpha B
- I
ethinylestradiol I
on O
the O
neutral O
and O
acidic O
pathways O
of O
bile B
salt I
synthesis O
in O
the O
rat O
. O

Effects O
of O
17alpha B
- I
ethinylestradiol I
( O
EE B
) O
on O
the O
neutral O
and O
acidic O
biosynthetic O
pathways O
of O
bile B
salt I
( O
BS O
) O
synthesis O
were O
evaluated O
in O
rats O
with O
an O
intact O
enterohepatic O
circulation O
and O
in O
rats O
with O
long O
- O
term O
bile O
diversion O
to O
induce O
BS O
synthesis O
. O

For O
this O
purpose O
, O
bile B
salt I
pool O
composition O
, O
synthesis O
of O
individual O
BS O
in O
vivo O
, O
hepatic O
activities O
, O
and O
expression O
levels O
of O
cholesterol B
7alpha O
- O
hydroxylase O
( O
CYP7A O
) O
, O
and O
sterol B
27 O
- O
hydroxylase O
( O
CYP27 O
) O
, O
as O
well O
as O
of O
other O
enzymes O
involved O
in O
BS O
synthesis O
, O
were O
analyzed O
in O
rats O
treated O
with O
EE B
( O
5 O
mg O
/ O
kg O
, O
3 O
days O
) O
or O
its O
vehicle O
. O

BS O
pool O
size O
was O
decreased O
by O
27 O
% O
but O
total O
BS O
synthesis O
was O
not O
affected O
by O
EE B
in O
intact O
rats O
. O

Synthesis O
of O
cholate B
was O
reduced O
by O
68 O
% O
in O
EE B
- O
treated O
rats O
, O
while O
that O
of O
chenodeoxycholate B
was O
increased O
by O
60 O
% O
. O

The O
recently O
identified O
Delta22 O
- O
isomer O
of O
beta B
- I
muricholate I
contributed O
for O
5 O
. O
4 O
% O
and O
18 O
. O
3 O
% O
( O
P O
< O
0 O
. O
01 O
) O
to O
the O
pool O
in O
control O
and O
EE B
- O
treated O
rats O
, O
respectively O
, O
but O
could O
not O
be O
detected O
in O
bile O
after O
exhaustion O
of O
the O
pool O
. O

A O
clear O
reduction O
of O
BS O
synthesis O
was O
found O
in O
bile O
- O
diverted O
rats O
treated O
with O
EE B
, O
yet O
biliary O
BS O
composition O
was O
only O
minimally O
affected O
. O

Activity O
of O
CYP7A O
was O
decreased O
by O
EE B
in O
both O
intact O
and O
bile O
- O
diverted O
rats O
, O
whereas O
the O
activity O
of O
the O
CYP27 O
was O
not O
affected O
. O

Hepatic O
mRNA O
levels O
of O
CYP7A O
were O
significantly O
reduced O
by O
EE B
in O
bile O
- O
diverted O
rats O
only O
; O
CYP27 O
mRNA O
levels O
were O
not O
affected O
by O
EE B
. O

In O
addition O
, O
mRNA O
levels O
of O
sterol B
12alpha O
- O
hydroxylase O
and O
lithocholate B
6beta O
- O
hydroxylase O
were O
increased O
by O
bile O
diversion O
and O
suppressed O
by O
EE B
. O

This O
study O
shows O
that O
17alpha B
- I
ethinylestradiol I
( O
EE B
) O
- O
induced O
intrahepatic O
cholestasis O
in O
rats O
is O
associated O
with O
selective O
inhibition O
of O
the O
neutral O
pathway O
of O
bile B
salt I
( O
BS O
) O
synthesis O
. O

Simultaneous O
impairment O
of O
other O
enzymes O
in O
the O
BS O
biosynthetic O
pathways O
may O
contribute O
to O
overall O
effects O
of O
EE B
on O
BS O
synthesis O
. O

Glibenclamide B
- O
sensitive O
hypotension O
produced O
by O
helodermin B
assessed O
in O
the O
rat O
. O

The O
effects O
of O
helodermin B
, O
a O
basic O
35 O
- O
amino O
acid O
peptide O
isolated O
from O
the O
venom O
of O
a O
lizard O
salivary O
gland O
, O
on O
arterial O
blood O
pressure O
and O
heart O
rate O
were O
examined O
in O
the O
rat O
, O
focusing O
on O
the O
possibility O
that O
activation O
of O
ATP B
sensitive O
K B
+ O
( O
K B
( O
ATP B
) O
) O
channels O
is O
involved O
in O
the O
responses O
. O

The O
results O
were O
also O
compared O
with O
those O
of O
vasoactive O
intestinal O
polypeptide O
( O
VIP O
) O
. O

Helodermin B
produced O
hypotension O
in O
a O
dose O
- O
dependent O
manner O
with O
approximately O
similar O
potency O
and O
duration O
to O
VIP O
. O

Hypotension O
induced O
by O
both O
peptides O
was O
significantly O
attenuated O
by O
glibenclamide B
, O
which O
abolished O
a O
levcromakalim B
- O
produced O
decrease O
in O
arterial O
blood O
pressure O
. O

Oxyhemoglobin O
did O
not O
affect O
helodermin B
- O
induced O
hypotension O
, O
whereas O
it O
shortened O
the O
duration O
of O
acetylcholine B
( O
ACh B
) O
- O
produced O
hypotension O
. O

These O
findings O
suggest O
that O
helodermin B
- O
produced O
hypotension O
is O
partly O
attributable O
to O
the O
activation O
of O
glibenclamide B
- O
sensitive O
K B
+ O
channels O
( O
K B
( O
ATP B
) O
channels O
) O
, O
which O
presumably O
exist O
on O
arterial O
smooth O
muscle O
cells O
. O

EDRF O
( O
endothelium O
- O
derived O
relaxing O
factor O
) O
/ O
nitric B
oxide I
does O
not O
seem O
to O
play O
an O
important O
role O
in O
the O
peptide O
- O
produced O
hypotension O
. O

Long O
- O
term O
efficacy O
and O
adverse O
event O
of O
nifedipine B
sustained O
- O
release O
tablets O
for O
cyclosporin B
A I
- O
induced O
hypertension O
in O
patients O
with O
psoriasis O
. O

Thirteen O
psoriatic O
patients O
with O
hypertension O
during O
the O
course O
of O
cyclosporin B
A I
therapy O
were O
treated O
for O
25 O
months O
with O
a O
calcium B
channel O
blocker O
, O
sustained O
- O
release O
nifedipine B
, O
to O
study O
the O
clinical O
antihypertensive O
effects O
and O
adverse O
events O
during O
treatment O
with O
both O
drugs O
. O

Seven O
of O
the O
13 O
patients O
had O
exhibited O
a O
subclinical O
hypertensive O
state O
before O
cyclosporin B
A I
therapy O
. O

Both O
systolic O
and O
diastolic O
blood O
pressures O
of O
these O
13 O
patients O
were O
decreased O
significantly O
after O
4 O
weeks O
of O
nifedipine B
therapy O
, O
and O
blood O
pressure O
was O
maintained O
within O
the O
normal O
range O
thereafter O
for O
25 O
months O
. O

The O
adverse O
events O
during O
combined O
therapy O
with O
cyclosporin B
A I
and O
nifedipine B
included O
an O
increase O
in O
blood B
urea I
nitrogen I
levels O
in O
9 O
of O
the O
13 O
patients O
and O
development O
of O
gingival O
hyperplasia O
in O
2 O
of O
the O
13 O
patients O
. O

Our O
findings O
indicate O
that O
sustained O
- O
release O
nifedipine B
is O
useful O
for O
hypertensive O
psoriatic O
patients O
under O
long O
- O
term O
treatment O
with O
cyclosporin B
A I
, O
but O
that O
these O
patients O
should O
be O
monitored O
for O
gingival O
hyperplasia O
. O