Input: Nimodipine prevents memory impairment caused by nitroglycerin - induced hypotension in adult mice. BACKGROUND: Hypotension and a resultant decrease in cerebral blood flow have been implicated in the development of cognitive dysfunction. We tested the hypothesis that nimodipine (NIMO) administered at the onset of nitroglycerin (NTG) - induced hypotension would preserve long - term associative memory. METHODS: The passive avoidance (PA) paradigm was used to assess memory retention. For PA training, latencies (seconds) were recorded for entry from a suspended platform into a Plexiglas tube where a shock was automatically delivered. Latencies were recorded 48 h later for a testing trial. Ninety - six Swiss - Webster mice (30 - 35 g, 6 - 8 wk), were randomized into 6 groups 1) saline (control), 2) NTG immediately after learning, 3) NTG 3 h after learning, 4) NTG and NIMO, 5) vehicle, and 6) NIMO alone. The extent of hypotension and changes in brain tissue oxygenation (PbtO (2)) and in cerebral blood flow were studied in a separate group of animals. RESULTS: All groups exhibited similar training latencies (17. 0 + / - 4. 6 s). Mice subjected to hypotensive episodes showed a significant decrease in latency time (178 + / - 156 s) compared with those injected with saline, NTG + NIMO, or delayed NTG (580 + / - 81 s, 557 + / - 67 s, and 493 + / - 146 s, respectively). A Kruskal - Wallis 1 - way analysis of variance indicated a significant difference among the 4 treatment groups (H = 15. 34; P < 0. 001). In a separate group of mice not subjected to behavioral studies, the same dose of NTG (n = 3) and NTG + NIMO (n = 3) caused mean arterial blood pressure to decrease from 85. 9 + / - 3. 8 mm Hg sem to 31. 6 + / - 0. 8 mm Hg sem and from 86. 2 + / - 3. 7 mm Hg sem to 32. 6 + / - 0. 2 mm Hg sem, respectively. Mean arterial blood pressure in mice treated with NIMO alone decreased from 88. 1 + / - 3. 8 mm Hg to 80. 0 + / - 2. 9 mm Hg. The intergroup difference was statistically significant (P < 0. 05). PbtO (2) decreased from 51. 7 + / - 4. 5 mm Hg sem to 33. 8 + / - 5. 2 mm Hg sem in the NTG group and from 38. 6 + / - 6. 1 mm Hg sem to 25. 4 + / - 2. 0 mm Hg sem in the NTG + NIMO groups, respectively. There were no significant differences among groups. CONCLUSION: In a PA retention paradigm, the injection of NTG immediately after learning produced a significant impairment of long - term associative memory in mice, whereas delayed induced hypotension had no effect. NIMO attenuated the disruption in consolidation of long - term memory caused by NTG but did not improve latency in the absence of hypotension. The observed effect of NIMO may have been attributable to the preservation of calcium homeostasis during hypotension, because there were no differences in the PbtO (2) indices among groups.

Nimodipine

nitroglycerin

nimodipine

NIMO

nitroglycerin

NTG

NTG

NTG

NTG

NIMO

NIMO

NTG

NIMO

NTG

NTG

NTG

NIMO

NIMO

NTG

NTG

NIMO

NTG

NIMO

NTG

NIMO

calcium

memory impairment

hypotension

Hypotension

cognitive dysfunction

hypotension

hypotension

hypotensive

hypotension

hypotension

hypotension

nitroglycerin

memory impairment

nitroglycerin

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

NTG

memory impairment

nitroglycerin

hypotension

nitroglycerin

Hypotension

nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

hypotensive

nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

Hypotension

nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

hypotensive

nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotension

NTG

Hypotension

NTG

hypotension

NTG

hypotension

NTG

hypotensive

NTG

hypotension

NTG

hypotension

NTG

hypotension


Input: Fatal haemopericardium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin. We report a case of fatal internal haemorrhage in an elderly man who consumed only cranberry juice for two weeks while maintaining his usual dosage of warfarin. We propose that naturally occurring compounds such as flavonoids, which are present in fruit juices, may increase the potency of warfarin by competing for the enzymes that normally inactivate warfarin. While traditionally regarded as foodstuffs, consumption of fruit juices should be considered when patients develop adverse drug reactions.

haemopericardium

gastrointestinal haemorrhage

haemorrhage

warfarin

warfarin

flavonoids

warfarin

warfarin

flavonoids

gastrointestinal haemorrhage

warfarin

gastrointestinal haemorrhage

warfarin

gastrointestinal haemorrhage

warfarin

gastrointestinal haemorrhage

warfarin

gastrointestinal haemorrhage


Input: Isoproterenol induces primary loss of dystrophin in rat hearts: correlation with myocardial injury. The mechanism of isoproterenol - induced myocardial damage is unknown, but a mismatch of oxygen supply vs. demand following coronary hypotension and myocardial hyperactivity is the best explanation for the complex morphological alterations observed. Severe alterations in the structural integrity of the sarcolemma of cardiomyocytes have been demonstrated to be caused by isoproterenol. Taking into account that the sarcolemmal integrity is stabilized by the dystrophin - glycoprotein complex (DGC) that connects actin and laminin in contractile machinery and extracellular matrix and by integrins, this study tests the hypothesis that isoproterenol affects sarcolemmal stability through changes in the DGC and integrins. We found different sensitivity of the DGC and integrin to isoproterenol subcutaneous administration. Immunofluorescent staining revealed that dystrophin is the most sensitive among the structures connecting the actin in the cardiomyocyte cytoskeleton and the extracellular matrix. The sarcomeric actin dissolution occurred after the reduction or loss of dystrophin. Subsequently, after lysis of myofilaments, gamma - sarcoglycan, beta - dystroglycan, beta1 - integrin, and laminin alpha - 2 expressions were reduced followed by their breakdown, as epiphenomena of the myocytolytic process. In conclusion, administration of isoproterenol to rats results in primary loss of dystrophin, the most sensitive among the structural proteins that form the DGC that connects the extracellular matrix and the cytoskeleton in cardiomyocyte. These changes, related to ischaemic injury, explain the severe alterations in the structural integrity of the sarcolemma of cardiomyocytes and hence severe and irreversible injury induced by isoproterenol.

Isoproterenol

isoproterenol

oxygen

isoproterenol

isoproterenol

isoproterenol

isoproterenol

isoproterenol

myocardial injury

myocardial damage

hypotension

myocardial hyperactivity

ischaemic injury

Isoproterenol

myocardial injury

Isoproterenol

myocardial damage

Isoproterenol

myocardial hyperactivity

isoproterenol

myocardial injury

isoproterenol

myocardial damage

isoproterenol

myocardial hyperactivity

isoproterenol

myocardial injury

isoproterenol

myocardial damage

isoproterenol

myocardial hyperactivity

isoproterenol

myocardial injury

isoproterenol

myocardial damage

isoproterenol

myocardial hyperactivity

isoproterenol

myocardial injury

isoproterenol

myocardial damage

isoproterenol

myocardial hyperactivity

isoproterenol

myocardial injury

isoproterenol

myocardial damage

isoproterenol

myocardial hyperactivity

isoproterenol

myocardial injury

isoproterenol

myocardial damage

isoproterenol

myocardial hyperactivity

Isoproterenol

ischaemic injury

isoproterenol

ischaemic injury

isoproterenol

ischaemic injury

isoproterenol

ischaemic injury

isoproterenol

ischaemic injury

isoproterenol

ischaemic injury

isoproterenol

ischaemic injury


Input: High fat diet - fed obese rats are highly sensitive to doxorubicin - induced cardiotoxicity. Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin - induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty - acid oxidation, ATP synthesis, and upregulated JAK / STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague - Dawley rats (250 - 275 g), sensitizes to doxorubicin - induced cardiotoxicity. A LD (10) dose (8 mg doxorubicin / kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet - fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor - alpha, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty - acid oxidation (666. 9 + / - 14. 0 nmol / min / g heart in ND versus 400. 2 + / - 11. 8 nmol / min / g heart in OB), (5) decreased mitochondrial AMP - alpha2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP / ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK / STAT3 pathway. In conclusion, HFD - induced obese rats are highly sensitized to doxorubicin - induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK / STAT3 pathway.

fat

doxorubicin

doxorubicin

Adriamycin

doxorubicin

triglycerides

ATP

fat

doxorubicin

doxorubicin

Doxorubicin

doxorubicin

doxorubicinol

AMP

ATP

ATP

ADP

doxorubicin

doxorubicin

ATP

obese

cardiotoxicity

cardiotoxicity

cardiotoxicity

obesity

cardiotoxicity

cardiotoxicity

cardiac dysfunction

obese

OB

renal or hepatic toxicity

renal or hepatic toxicity

hepatic toxicity

OB

OB

OB

obese

cardiotoxicity

fat

obese

fat

obesity

fat

obese

fat

OB

fat

OB

fat

OB

fat

OB

fat

obese

fat

obese

fat

obesity

fat

obese

fat

OB

fat

OB

fat

OB

fat

OB

fat

obese

doxorubicin

cardiac dysfunction

doxorubicin

cardiac dysfunction

Adriamycin

cardiac dysfunction

doxorubicin

cardiac dysfunction

doxorubicin

cardiac dysfunction

doxorubicin

cardiac dysfunction

Doxorubicin

cardiac dysfunction

doxorubicin

cardiac dysfunction

doxorubicin

cardiac dysfunction

doxorubicin

cardiac dysfunction


Input: Complete atrioventricular block secondary to lithium therapy. Sinus node dysfunction has been reported most frequently among the adverse cardiovascular effects of lithium. In the present case, complete atrioventricular (AV) block with syncopal attacks developed secondary to lithium therapy, necessitating permanent pacemaker implantation. Serum lithium levels remained under or within the therapeutic range during the syncopal attacks. Lithium should be used with extreme caution, especially in patients with mild disturbance of AV conduction.

atrioventricular block

Sinus node dysfunction

atrioventricular (AV) block

syncopal attacks

syncopal attacks

lithium

lithium

lithium

lithium

Lithium

lithium

Sinus node dysfunction

lithium

Sinus node dysfunction

lithium

Sinus node dysfunction

lithium

Sinus node dysfunction

Lithium

Sinus node dysfunction

lithium

atrioventricular block

lithium

atrioventricular (AV) block

lithium

atrioventricular block

lithium

atrioventricular (AV) block

lithium

atrioventricular block

lithium

atrioventricular (AV) block

lithium

atrioventricular block

lithium

atrioventricular (AV) block

Lithium

atrioventricular block

Lithium

atrioventricular (AV) block


Input: Neuroleptic malignant syndrome induced by ziprasidone on the second day of treatment. Neuroleptic malignant syndrome (NMS) is the rarest and most serious of the neuroleptic - induced movement disorders. We describe a case of neuroleptic malignant syndrome (NMS) associated with the use of ziprasidone. Although conventional neuroleptics are more frequently associated with NMS, atypical antipsychotic drugs like ziprasidone may also be a cause. The patient is a 24 - year - old male with a history of schizophrenia who developed signs and symptoms of NMS after 2 days of treatment with an 80 - mg / day dose of orally administrated ziprasidone. This case is the earliest (second day of treatment) NMS due to ziprasidone reported in the literature.

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome

NMS

movement disorders

neuroleptic malignant syndrome

NMS

NMS

schizophrenia

NMS

NMS

ziprasidone

ziprasidone

ziprasidone

ziprasidone

ziprasidone

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

Neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

neuroleptic malignant syndrome

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS

ziprasidone

NMS


Input: Role of mangiferin on biochemical alterations and antioxidant status in isoproterenol - induced myocardial infarction in rats. The current study dealt with the protective role of mangiferin, a polyphenol from Mangifera indica Linn. (Anacardiaceae), on isoproterenol (ISPH) - induced myocardial infarction (MI) in rats through its antioxidative mechanism. Subcutaneous injection of ISPH (200 mg / kg body weight in 1 ml saline) to rats for 2 consecutive days caused myocardial damage in rat heart, which was determined by the increased activity of serum lactate dehydrogenase (LDH) and creatine phosphokinase isoenzymes (CK - MB), increased uric acid level and reduced plasma iron binding capacity. The protective role of mangiferin was analyzed by triphenyl tetrazolium chloride (TTC) test used for macroscopic enzyme mapping assay of the ischemic myocardium. The heart tissue antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase and glutathione reductase activities, non - enzymic antioxidants such as cerruloplasmin, Vitamin C, Vitamin E and glutathione levels were altered in MI rats. Upon pretreatment with mangiferin (100 mg / kg body weight suspended in 2 ml of dimethyl sulphoxide) given intraperitoneally for 28 days to MI rats protected the above - mentioned parameters to fall from the normal levels. Activities of heart tissue enzymic antioxidants and serum non - enzymic antioxidants levels rose significantly upon mangiferin administration as compared to ISPH - induced MI rats. From the present study it is concluded that mangiferin exerts a beneficial effect against ISPH - induced MI due to its antioxidant potential, which regulated the tissues defense system against cardiac damage.

mangiferin

isoproterenol

mangiferin

polyphenol

isoproterenol

ISPH

ISPH

lactate

creatine

uric acid

iron

mangiferin

triphenyl tetrazolium chloride

TTC

superoxide

glutathione

glutathione

glutathione

Vitamin C

Vitamin E

glutathione

mangiferin

dimethyl sulphoxide

mangiferin

ISPH

mangiferin

ISPH

myocardial infarction

myocardial infarction

MI

myocardial damage

ischemic myocardium

MI

MI

MI

MI

cardiac damage

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

MI

isoproterenol

MI

isoproterenol

MI

isoproterenol

MI

isoproterenol

MI

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

MI

isoproterenol

MI

isoproterenol

MI

isoproterenol

MI

isoproterenol

MI

ISPH

myocardial infarction

ISPH

myocardial infarction

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

myocardial infarction

ISPH

myocardial infarction

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

myocardial infarction

ISPH

myocardial infarction

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

myocardial infarction

ISPH

myocardial infarction

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

MI

ISPH

MI


Input: Remifentanil pretreatment reduces myoclonus after etomidate. STUDY OBJECTIVE: The aim of the study was to compare the effect of pretreatment with remifentanil 1 microg / kg and the effect of gender on the incidence of myoclonus after anesthesia induction with etomidate. DESIGN: This was a randomized, double - blind study. SETTING: The study was conducted at a university hospital. PATIENTS: Sixty patients were pretreated in a randomized double - blinded fashion with remifentanil 1 microg / kg or placebo. Two minutes after remifentanil or placebo injection, etomidate 0. 3 mg / kg was given. MEASUREMENTS: Myoclonus was recorded with a scale of 0 to 3. The grade of sedation (none, mild, moderate, severe), nausea, pruritus, and apnea were recorded after injection of both drugs. MAIN RESULTS: The incidence of myoclonus was significantly lower in the remifentanil group (6. 7%) than in the placebo group (70%) (P < 0. 001). None of the patients experienced sedation, apnea, nausea, or pruritus after injection of both drugs. In the placebo group, male patients were associated with significantly increased incidence of myoclonus after etomidate administration. CONCLUSION: Pretreatment with remifentanil 1 microg / kg reduced myoclonus after etomidate induction without side effects such as sedation, apnea, nausea, or pruritus. Men experience increased incidence of myoclonus than women after etomidate administration.

Remifentanil

etomidate

remifentanil

etomidate

remifentanil

remifentanil

etomidate

remifentanil

etomidate

remifentanil

etomidate

etomidate

myoclonus

myoclonus

Myoclonus

nausea

pruritus

apnea

myoclonus

apnea

nausea

pruritus

myoclonus

myoclonus

apnea

nausea

pruritus

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

Myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

Myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

Myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

Myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

Myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

Myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus

etomidate

myoclonus


Input: Daidzein activates choline acetyltransferase from MC - IXC cells and improves drug - induced amnesia. The choline acetyltransferase (ChAT) activator, which enhances cholinergic transmission via an augmentation of the enzymatic production of acetylcholine (ACh), is an important factor in the treatment of Alzheimer' s disease (AD). Methanolic extracts from Pueraria thunbergiana exhibited an activation effect (46%) on ChAT in vitro. Via the sequential isolation of Pueraria thunbergiana, the active component was ultimately identified as daidzein (4', 7 - dihydroxy - isoflavone). In order to investigate the effects of daidzein from Pueraria thunbergiana on scopolamine - induced impairments of learning and memory, we conducted a series of in vivo tests. Administration of daidzein (4. 5 mg / kg body weight) to mice was shown significantly to reverse scopolamine - induced amnesia, according to the results of a Y - maze test. Injections of scopolamine into mice resulted in impaired performance on Y - maze tests (a 37% decreases in alternation behavior). By way of contrast, mice treated with daidzein prior to the scopolamine injections were noticeably protected from this performance impairment (an approximately 12% - 21% decrease in alternation behavior). These results indicate that daidzein might play a role in acetylcholine biosynthesis as a ChAT activator, and that it also ameliorates scopolamine - induced amnesia.

Daidzein

choline

choline

acetylcholine

ACh

daidzein

4', 7 - dihydroxy - isoflavone

daidzein

scopolamine

daidzein

scopolamine

scopolamine

daidzein

scopolamine

daidzein

acetylcholine

scopolamine

amnesia

Alzheimer' s disease

AD

impairments of learning and memory

impairments of learning

impairments of learning and memory

amnesia

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia


Input: Possible azithromycin - associated hiccups. OBJECTIVE: To report a case of persistent hiccups associated by azithromycin therapy. CASE SUMMARY: A 76 - year - old man presented with persistent hiccups after beginning azithromycin for the treatment of pharyngitis. Hiccups were persistent and exhausting. Discontinuation of azithromycin and therapy with baclofen finally resolved hiccups. No organic cause of hiccups was identified despite extensive investigation. DISCUSSION: Pharmacotherapeutic agents have been uncommonly associated with hiccups. Corticosteroids (dexamethasone and methylprednisolone), benzodiazepines (midazolam) and general anaesthesia have been the specific agents mentioned most frequently in the literature as being associated with the development of hiccups. Few cases of drug - induced hiccups have been reported related to macrolide antimicrobials. Using the Naranjo adverse effect reaction probability scale this event could be classified as possible (score 5 points), mostly because of the close temporal sequence, previous reports on this reaction with other macrolides and the absence of any alternative explanation for hiccups. Our hypothesis is that a vagal mechanism mediated by azithromycin could be the pathogenesis of hiccups in our patient. CONCLUSIONS: Diagnosis of drug - induced hiccups is difficult and often achieved only by a process of elimination. However, macrolide antimicrobials have been reported to be associated with hiccups and vagal mechanism could explain the development of this side - effect.

azithromycin

azithromycin

azithromycin

azithromycin

baclofen

dexamethasone

methylprednisolone

benzodiazepines

midazolam

macrolide

macrolides

azithromycin

macrolide

hiccups

hiccups

hiccups

pharyngitis

Hiccups

hiccups

hiccups

hiccups

hiccups

hiccups

hiccups

hiccups

hiccups

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

Hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

Hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

Hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

Hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

Hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

azithromycin

hiccups

baclofen

hiccups

baclofen

hiccups

baclofen

hiccups

baclofen

Hiccups

baclofen

hiccups

baclofen

hiccups

baclofen

hiccups

baclofen

hiccups

baclofen

hiccups

baclofen

hiccups

baclofen

hiccups

baclofen

hiccups

baclofen

hiccups


Input: Time trends in warfarin - associated hemorrhage. The annual incidence of warfarin - related bleeding at Brigham and Women' s Hospital increased from 0. 97 / 1, 000 patient admissions in the first time period (January 1995 to October 1998) to 1. 19 / 1, 000 patient admissions in the second time period (November 1998 to August 2002) of this study. The proportion of patients with major and intracranial bleeding increased from 20. 2% and 1. 9%, respectively, in the first time period, to 33. 3% and 7. 8%, respectively, in the second.

warfarin

warfarin

hemorrhage

bleeding

intracranial bleeding

warfarin

intracranial bleeding

warfarin

intracranial bleeding

warfarin

hemorrhage

warfarin

bleeding

warfarin

hemorrhage

warfarin

bleeding


Input: Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy. Haemorrhagic myocarditis is a rare but important complication of cyclophosphamide therapy. Echocardiographic identification of the disorder can be made. We believe that the ultrasound features of this disorder have not been previously reported.

haemorrhagic myocarditis

haemorrhagic

myocarditis

Haemorrhagic myocarditis

Haemorrhagic

myocarditis

cyclophosphamide

cyclophosphamide

cyclophosphamide

haemorrhagic myocarditis

cyclophosphamide

myocarditis

cyclophosphamide

Haemorrhagic myocarditis

cyclophosphamide

myocarditis

cyclophosphamide

haemorrhagic myocarditis

cyclophosphamide

myocarditis

cyclophosphamide

Haemorrhagic myocarditis

cyclophosphamide

myocarditis

cyclophosphamide

haemorrhagic

cyclophosphamide

Haemorrhagic

cyclophosphamide

haemorrhagic

cyclophosphamide

Haemorrhagic


Input: Glyceryl trinitrate induces attacks of migraine without aura in sufferers of migraine with aura. Migraine with aura and migraine without aura have the same pain phase, thus indicating that migraine with aura and migraine without aura share a common pathway of nociception. In recent years, increasing evidence has suggested that the messenger molecule nitric oxide (NO) is involved in pain mechanisms of migraine without aura. In order to clarify whether the same is true for migraine with aura, in the present study we examined the headache response to intravenous infusion of glyceryl trinitrate (GTN) (0. 5 microg / kg / min for 20 min) in 12 sufferers of migraine with aura. The specific aim was to elucidate whether an aura and / or an attack of migraine without aura could be induced. Fourteen healthy subjects served as controls. Aura symptoms were not elicited in any subject. Headache was more severe in migraineurs than in the controls during and immediately after GTN infusion (p = 0. 037) as well as during the following 11 h (p = 0. 008). In the controls, the GTN - induced headache gradually disappeared, whereas in migraineurs peak headache intensity occurred at a mean time of 240 min post - infusion. At this time the induced headache in 6 of 12 migraineurs fulfilled the diagnostic criteria for migraine without aura of the International Headache Society. The results therefore suggest that NO is involved in the pain mechanisms of migraine with aura. Since cortical spreading depression has been shown to liberate NO in animals, this finding may help our understanding of the coupling between cortical spreading depression and headache in migraine with aura.

Glyceryl trinitrate

nitric oxide

NO

glyceryl trinitrate

GTN

GTN

GTN

NO

NO

migraine without aura

migraine with aura

Migraine with aura

migraine without aura

pain

migraine with aura

migraine without aura

pain

migraine without aura

migraine with aura

headache

migraine with aura

migraine without aura

Headache

migraineurs

headache

migraineurs

headache

headache

migraineurs

migraine without aura

Headache

pain

migraine with aura

depression

depression

headache

migraine with aura

nitric oxide

migraine without aura

nitric oxide

migraine without aura

nitric oxide

migraine without aura

nitric oxide

migraine without aura

nitric oxide

migraine without aura

nitric oxide

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

NO

migraine without aura

Glyceryl trinitrate

migraine without aura

Glyceryl trinitrate

migraine without aura

Glyceryl trinitrate

migraine without aura

Glyceryl trinitrate

migraine without aura

Glyceryl trinitrate

migraine without aura

Glyceryl trinitrate

migraine without aura

glyceryl trinitrate

migraine without aura

glyceryl trinitrate

migraine without aura

glyceryl trinitrate

migraine without aura

glyceryl trinitrate

migraine without aura

glyceryl trinitrate

migraine without aura

glyceryl trinitrate

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura

GTN

migraine without aura


Input: Stroke and cocaine or amphetamine use. The association of cocaine and amphetamine use with hemorrhagic and ischemic stroke is based almost solely on data from case series. The limited number of epidemiologic studies of stroke and use of cocaine and / or amphetamine have been done in settings that serve mostly the poor and / or minorities. This case - control study was conducted in the defined population comprising members of Kaiser Permanente of Northern and Southern California. We attempted to identify all incident strokes in women ages 15 - 44 years during a 3 - year period using hospital admission and discharge records, emergency department logs, and payment requests for out - of - plan hospitalizations. We selected controls, matched on age and facility of usual care, at random from healthy members of the health plan. We obtained information in face - to - face interviews. There were 347 confirmed stroke cases and 1, 021 controls. The univariate matched odds ratio for stroke in women who admitted to using cocaine and / or amphetamine was 8. 5 (95% confidence interval = 3. 6 - 20. 0). After further adjustment for potential confounders, the odds ratio in women who reported using cocaine and / or amphetamine was 7. 0 (95% confidence interval = 2. 8 - 17. 9). The use of cocaine and / or amphetamine is a strong risk factor for stroke in this socioeconomically heterogeneous, insured urban population.

Stroke

ischemic

stroke

stroke

strokes

stroke

stroke

stroke

cocaine

amphetamine

cocaine

amphetamine

cocaine

amphetamine

cocaine

amphetamine

cocaine

amphetamine

cocaine

amphetamine

cocaine

Stroke

cocaine

stroke

cocaine

stroke

cocaine

strokes

cocaine

stroke

cocaine

stroke

cocaine

stroke

cocaine

Stroke

cocaine

stroke

cocaine

stroke

cocaine

strokes

cocaine

stroke

cocaine

stroke

cocaine

stroke

cocaine

Stroke

cocaine

stroke

cocaine

stroke

cocaine

strokes

cocaine

stroke

cocaine

stroke

cocaine

stroke

cocaine

Stroke

cocaine

stroke

cocaine

stroke

cocaine

strokes

cocaine

stroke

cocaine

stroke

cocaine

stroke

cocaine

Stroke

cocaine

stroke

cocaine

stroke

cocaine

strokes

cocaine

stroke

cocaine

stroke

cocaine

stroke

cocaine

Stroke

cocaine

stroke

cocaine

stroke

cocaine

strokes

cocaine

stroke

cocaine

stroke

cocaine

stroke

amphetamine

Stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

strokes

amphetamine

stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

Stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

strokes

amphetamine

stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

Stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

strokes

amphetamine

stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

Stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

strokes

amphetamine

stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

Stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

strokes

amphetamine

stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

Stroke

amphetamine

stroke

amphetamine

stroke

amphetamine

strokes

amphetamine

stroke

amphetamine

stroke

amphetamine

stroke


Input: Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double - blind placebo - controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow - up. In June, 1997, the trialists and the data - monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention - to - treat. FINDINGS: 5408 women were randomised; participating women have a median follow - up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast - cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone - replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low - to - normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone - replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow - up to quantify the long - term risks and benefits of tamoxifen therapy.

breast cancer

breast cancer

endometrial cancer

breast cancer

breast cancer

breast cancer

breast cancer

breast - cancer

breast cancer

breast cancer

vascular events

hypertriglyceridaemia

breast cancer

breast cancer

tamoxifen

Tamoxifen

Tamoxifen

tamoxifen

tamoxifen

tamoxifen

tamoxifen

tamoxifen

tamoxifen

tamoxifen

tamoxifen

tamoxifen

tamoxifen

tamoxifen

vascular events

Tamoxifen

vascular events

Tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

vascular events

tamoxifen

hypertriglyceridaemia

Tamoxifen

hypertriglyceridaemia

Tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia

tamoxifen

hypertriglyceridaemia


Input: A measure of pupillary oscillation as a marker of cocaine - induced paranoia. Cocaine - induced paranoia (CIP) remains an important drug - induced model of idiopathic paranoia for which no psychophysiologic marker has yet emerged. Measures of pupillary oscillation were able to significantly distinguish a group of abstinent crack cocaine abusers endorsing past CIP (n = 32) from another group of crack addicts who denied past CIP (n = 29).

pupillary oscillation

paranoia

paranoia

CIP

paranoia

pupillary oscillation

CIP

CIP

cocaine

Cocaine

crack cocaine

crack

cocaine

pupillary oscillation

cocaine

pupillary oscillation

Cocaine

pupillary oscillation

Cocaine

pupillary oscillation

cocaine

paranoia

cocaine

paranoia

cocaine

CIP

cocaine

paranoia

cocaine

CIP

cocaine

CIP

Cocaine

paranoia

Cocaine

paranoia

Cocaine

CIP

Cocaine

paranoia

Cocaine

CIP

Cocaine

CIP


Input: Seizures induced by combined levomepromazine - fluvoxamine treatment. We report a case of combined levomepromazine - fluvoxamine treatment - induced seizures. It seems that combined treatment of fluvoxamine with phenothiazines may possess proconvulsive activity.

Seizures

seizures

levomepromazine

fluvoxamine

levomepromazine

fluvoxamine

fluvoxamine

phenothiazines

fluvoxamine

Seizures

fluvoxamine

seizures

fluvoxamine

Seizures

fluvoxamine

seizures

fluvoxamine

Seizures

fluvoxamine

seizures

levomepromazine

Seizures

levomepromazine

seizures

levomepromazine

Seizures

levomepromazine

seizures


Input: Why may epsilon - aminocaproic acid (EACA) induce myopathy in man? Report of a case and literature review. A case of necrotizing myopathy due to a short epsilon - aminocaproic acid (EACA) treatment in a 72 year - old patient with subarachnoid haemorrhage (SAH) is described. Pathogenetic hypotheses are discussed.

epsilon - aminocaproic acid

EACA

epsilon - aminocaproic acid

EACA

myopathy

necrotizing myopathy

necrotizing

myopathy

subarachnoid haemorrhage

SAH

epsilon - aminocaproic acid

necrotizing myopathy

epsilon - aminocaproic acid

necrotizing

EACA

necrotizing myopathy

EACA

necrotizing

epsilon - aminocaproic acid

necrotizing myopathy

epsilon - aminocaproic acid

necrotizing

EACA

necrotizing myopathy

EACA

necrotizing

epsilon - aminocaproic acid

myopathy

epsilon - aminocaproic acid

myopathy

EACA

myopathy

EACA

myopathy

epsilon - aminocaproic acid

myopathy

epsilon - aminocaproic acid

myopathy

EACA

myopathy

EACA

myopathy


Input: Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states. The H2 - histamine receptor antagonists ranitidine and cimetidine were compared for their abilities to control gastric acid hypersecretion on a short - and long - term basis in 22 patients with gastric acid hypersecretory states. Nineteen patients had Zollinger - Ellison syndrome, one patient had systemic mastocytosis, and two patients had idiopathic hypersecretion. The rates of onset of the action of cimetidine and ranitidine were the same. The actions of both drugs were increased by anticholinergic agents, and there was a close correlation between the daily maintenance dose of each drug needed to control acid secretion. However, ranitidine was threefold more potent than cimetidine both in acute inhibition studies and in the median maintenance dose needed (1. 2 g per day for ranitidine and 3. 6 g per day for cimetidine). Sixty percent of the males developed breast changes or impotence while taking cimetidine and in all cases these changes disappeared when cimetidine was replaced by ranitidine. Treatment with high doses of cimetidine (one to 60 months; median, 11 months) or ranitidine (two to 31 months; median, 14 months) was not associated with hepatic or hematologic toxicity or alterations of serum gastrin concentrations, but ranitidine therapy was associated with a significantly lower serum creatinine level than seen with cimetidine therapy. The results show that both drugs can adequately inhibit acid secretion in patients with gastric hypersecretory states. Both are safe at high doses, but ranitidine is threefold more potent and does not cause the antiandrogen side effects frequently seen with high doses of cimetidine.

ranitidine

cimetidine

histamine

ranitidine

cimetidine

cimetidine

ranitidine

ranitidine

cimetidine

ranitidine

cimetidine

cimetidine

cimetidine

ranitidine

cimetidine

ranitidine

ranitidine

creatinine

cimetidine

ranitidine

cimetidine

Zollinger - Ellison syndrome

systemic mastocytosis

impotence

hepatic or hematologic toxicity

hepatic or hematologic toxicity

hematologic toxicity

cimetidine

impotence

cimetidine

impotence

cimetidine

impotence

cimetidine

impotence

cimetidine

impotence

cimetidine

impotence

cimetidine

impotence

cimetidine

impotence

cimetidine

impotence

cimetidine

impotence


Input: A catch in the Reye. Twenty - six cases of Reye syndrome from The Children' s Hospital, Camperdown, Australia, occurring between 1973 and 1982 were reviewed. Of these, 20 cases met the US Public Health Service Centers for Disease Control criteria for the diagnosis of Reye syndrome. Aspirin or salicylate ingestion had occurred in only one of the 20 cases (5%), and paracetamol (acetaminophen) had been administered in only six of the cases (30%). Pathologic confirmation of the diagnosis of Reye syndrome was accomplished in 90% of the cases. The incidence of Reye syndrome in New South Wales, Australia, is estimated from this study to be approximately nine cases per 1 million children compared with recent US data of ten to 20 cases per 1 million children and three to seven cases per 1 million children in Great Britain. The mortality for these Reye syndrome cases in Australia was 45% as compared with a 32% case - fatality rate in the United States. In Australia, the pediatric usage of aspirin has been extremely low for the past 25 years (less than 1% of total dosage units sold), with paracetamol (acetaminophen) dominating the pediatric analgesic and antipyretic market. Reye syndrome may be disappearing from Australia despite a total lack of association with salicylates or aspirin ingestion, since there were no cases found at The Children' s Hospital in 1983, 1984, or 1985.

Reye

Reye syndrome

Reye syndrome

Reye syndrome

Reye syndrome

Reye syndrome

Reye syndrome

Aspirin

salicylate

paracetamol

acetaminophen

aspirin

paracetamol

acetaminophen

salicylates

aspirin

Aspirin

Reye

Aspirin

Reye syndrome

Aspirin

Reye syndrome

Aspirin

Reye syndrome

Aspirin

Reye syndrome

Aspirin

Reye syndrome

Aspirin

Reye syndrome

aspirin

Reye

aspirin

Reye syndrome

aspirin

Reye syndrome

aspirin

Reye syndrome

aspirin

Reye syndrome

aspirin

Reye syndrome

aspirin

Reye syndrome

aspirin

Reye

aspirin

Reye syndrome

aspirin

Reye syndrome

aspirin

Reye syndrome

aspirin

Reye syndrome

aspirin

Reye syndrome

aspirin

Reye syndrome


Input: St. Anthony' s fire, then and now: a case report and historical review. A rare case of morbid vasospasm, together with striking angiographic findings, is described secondary to the ingestion of methysergide by a 48 - year - old woman. A brief review of the literature on similar cases is presented. A discussion of the history of ergot includes its original discovery, the epidemics of gangrene that it has caused through the ages and its past and present role in the management of migraine headache. Despite the advent of calcium channel blockers and beta - adrenergic antagonists, ergot preparations continue to play a major role in migraine therapy, so that the danger of St. Anthony' s fire persists.

St. Anthony' s fire

vasospasm

gangrene

migraine headache

migraine

St. Anthony' s fire

methysergide

ergot

calcium

ergot

ergot

migraine headache

ergot

migraine

ergot

migraine headache

ergot

migraine

methysergide

vasospasm


Input: Beta - 2 - adrenoceptor - mediated hypokalemia and its abolishment by oxprenolol. The time course and concentration - effect relationship of terbutaline - induced hypokalemia was studied, using computer - aided pharmacokinetic - dynamic modeling. Subsequently we investigated the efficacy of oxprenolol in antagonizing such hypokalemia, together with the pharmacokinetic interaction between both drugs. Six healthy subjects were given a 0. 5 mg subcutaneous dose of terbutaline on two occasions: 1 hour after oral administration of a placebo and 1 hour after 80 mg oxprenolol orally. In the 7 - hour period after terbutaline administration, plasma samples were taken for determination of plasma potassium levels and drug concentrations. The sigmoid Emax model offered a good description of the relation between terbutaline concentrations and potassium effects. Oxprenolol caused decreases of 65% and 56% of terbutaline volume of distribution and clearance, respectively, and an increase of 130% of its AUC. In spite of higher terbutaline concentrations after oxprenolol pretreatment, the hypokalemia was almost completely antagonized by the beta 2 - blocking action.

hypokalemia

hypokalemia

hypokalemia

hypokalemia

oxprenolol

terbutaline

oxprenolol

terbutaline

oxprenolol

terbutaline

potassium

terbutaline

potassium

Oxprenolol

terbutaline

terbutaline

oxprenolol

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia

terbutaline

hypokalemia


Input: Midline B3 serotonin nerves in rat medulla are involved in hypotensive effect of methyldopa. Previous experiments in this laboratory have shown that microinjection of methyldopa onto the ventrolateral cells of the B3 serotonin neurons in the medulla elicits a hypotensive response mediated by a projection descending into the spinal cord. The present experiments were designed to investigate the role of the midline cells of the B3 serotonin neurons in the medulla, coinciding with the raphe magnus. In spontaneously hypertensive, stroke - prone rats, microinjection of methyldopa into the area of the midline B3 serotonin cell group in the ventral medulla caused a potent hypotension of 30 - 40 mm Hg, which was maximal 2 - 3 h after administration and was abolished by the serotonin neurotoxin 5, 7 - dihydroxytryptamine (5, 7 - DHT) injected intracerebroventricularly. However, intraspinal injection of 5, 7 - DHT to produce a more selective lesion of only descending serotonin projections in the spinal cord did not affect this hypotension. Further, 5, 7 - DHT lesion of serotonin nerves travelling in the median forebrain bundle, one of the main ascending pathways from the B3 serotonin cells, did not affect the fall in blood pressure associated with a midline B3 serotonin methyldopa injection. It is concluded therefore that, unlike the ventrolateral B3 cells which mediate a methyldopa - induced hypotension via descending projections, the midline serotonin B3 cells in the medulla contribute to the hypotensive action of methyldopa, either by way of an ascending projection which does not pass through the median forebrain bundle, or through a projection restricted to the caudal brainstem.

serotonin

methyldopa

methyldopa

serotonin

serotonin

methyldopa

serotonin

serotonin

5, 7 - dihydroxytryptamine

5, 7 - DHT

5, 7 - DHT

serotonin

5, 7 - DHT

serotonin

serotonin

serotonin

methyldopa

methyldopa

serotonin

methyldopa

hypotensive

hypotensive

hypertensive

stroke

hypotension

hypotension

hypotension

hypotensive

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotensive

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotension

methyldopa

hypotensive


Input: Yohimbine treatment of sexual side effects induced by serotonin reuptake blockers. BACKGROUND: Preclinical and clinical studies suggest that yohimbine facilitates sexual behavior and may be helpful in the treatment of male impotence. A single case report suggests that yohimbine may be used to treat the sexual side effects of clomipramine. This study evaluated yohimbine as a treatment for the sexual side effects caused by serotonin reuptake blockers. METHOD: Six patients with either obsessive compulsive disorder, trichotillomania, anxiety, or affective disorders who suffered sexual side effects after treatment with serotonin reuptake blockers were given yohimbine on a p. r. n. basis in an open clinical trial. Various doses of yohimbine were used to determine the ideal dose for each patient. RESULTS: Five of the six patients experienced improved sexual functioning after taking yohimbine. One patient who failed to comply with yohimbine treatment had no therapeutic effects. Side effects of yohimbine included excessive sweating, increased anxiety, and a wound - up feeling in some patients. CONCLUSION: The results of this study indicate that yohimbine may be an effective treatment for the sexual side effects caused by serotonin reuptake blockers. Future controlled studies are needed to further investigate the effectiveness and safety of yohimbine for this indication.

Yohimbine

serotonin

yohimbine

yohimbine

clomipramine

yohimbine

serotonin

serotonin

yohimbine

yohimbine

yohimbine

yohimbine

yohimbine

yohimbine

serotonin

yohimbine

sexual side effects

male impotence

sexual side effects

sexual side effects

obsessive compulsive disorder

trichotillomania

anxiety

affective disorders

sexual side effects

anxiety

sexual side effects

clomipramine

sexual side effects

clomipramine

sexual side effects

clomipramine

sexual side effects

clomipramine

sexual side effects

clomipramine

sexual side effects


Input: Hypersensitivity immune reaction as a mechanism for dilevalol - associated hepatitis. OBJECTIVE: To assess lymphocyte reactivity to dilevalol and to serum containing putative ex vivo dilevalol antigens or metabolites in a case of dilevalol - induced liver injury. PATIENT: A 58 - year - old woman with a clinical diagnosis of dilevalol - induced liver injury. METHODS: Peripheral blood mononuclear cells collected from the patient were cultured in the presence of a solution of dilevalol and also with sera collected from a volunteer before and after dilevalol intake. A similar protocol was performed with lymphocytes from a healthy subject. RESULTS: No lymphocyte proliferation was observed either in the patient or in the healthy volunteer in the presence of dilevalol solutions. A significant proliferative response to serum collected after dilevalol intake was observed in the case of the patient compared with the proliferative response to the serum collected before the drug intake. No reactivity was found when lymphocytes from the healthy subject were tested under similar conditions. CONCLUSIONS: The methodology used allowed the detection of lymphocyte sensitization to sera containing ex vivo - prepared dilevalol antigens, suggesting the involvement of an immunologic mechanism in dilevalol - induced liver injury.

Hypersensitivity

hepatitis

liver injury

liver injury

liver injury

dilevalol

dilevalol

dilevalol

dilevalol

dilevalol

dilevalol

dilevalol

dilevalol

dilevalol

dilevalol

dilevalol

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

hepatitis

dilevalol

liver injury

dilevalol

liver injury

dilevalol

liver injury

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity

dilevalol

Hypersensitivity


Input: Reversible myocardial hypertrophy induced by tacrolimus in a pediatric heart transplant recipient: case report. Tacrolimus is a potent immunosuppressant that is frequently used in organ transplantation. However, adverse effects include cardiac toxicity. Herein we describe transient myocardial hypertrophy induced by tacrolimus after heart transplantation. The hypertrophy caused no clinical symptoms but was noted because of elevation of plasma brain natriuretic peptide concentration and confirmed at echocardiography. Initially, allograft rejection was feared; however, myocardial biopsy samples revealed only interstitial edema and mild myocardial hypertrophy; neither cellular nor humoral rejection was detected. The blood tacrolimus concentration was higher than usual at that time; thus, tacrolimus dosage was reduced. Myocardial hypertrophy completely resolved upon reducing the target concentration of tacrolimus and did not recur, as confirmed at echocardiography and myocardial biopsy. Thus, we conclude that tacrolimus induces reversible myocardial hypertrophy. In patients receiving tacrolimus therapy, blood concentration should be carefully controlled and extreme attention paid to cardiac involvement.

myocardial hypertrophy

cardiac toxicity

myocardial hypertrophy

hypertrophy

edema

myocardial hypertrophy

Myocardial hypertrophy

myocardial hypertrophy

tacrolimus

Tacrolimus

tacrolimus

tacrolimus

tacrolimus

tacrolimus

tacrolimus

tacrolimus

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

Myocardial hypertrophy

tacrolimus

myocardial hypertrophy

Tacrolimus

myocardial hypertrophy

Tacrolimus

myocardial hypertrophy

Tacrolimus

myocardial hypertrophy

Tacrolimus

Myocardial hypertrophy

Tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

Myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

Myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

Myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

Myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

Myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

myocardial hypertrophy

tacrolimus

Myocardial hypertrophy

tacrolimus

myocardial hypertrophy


Input: Comparison of unilateral pallidotomy and subthalamotomy findings in advanced idiopathic Parkinson' s disease. A prospective, randomized, double - blind pilot study to compare the results of stereotactic unilateral pallidotomy and subthalamotomy in advanced idiopathic Parkinson' s disease (PD) refractory to medical treatment was designed. Ten consecutive patients (mean age, 58. 4 + / - 6. 8 years; 7 men, 3 women) with similar characteristics at the duration of disease (mean disease time, 8. 4 + / - 3. 5 years), disabling motor fluctuations (Hoehn _ Yahr stage 3 - 5 in off - drug phases) and levodopa - induced dyskinesias were selected. All patients had bilateral symptoms and their levodopa equivalent dosing were analysed. Six patients were operated on in the globus pallidus interna (GPi) and four in the subthalamic nucleus (STN). Clinical evaluation included the use of the Unified Parkinson' s Disease Rating Scale (UPDRS), Hoehn_Yahr score and Schwab England activities of daily living (ADL) score in' on' - and' off' - drug conditions before surgery and 6 months after surgery. There was statistically significant improvement in all contralateral major parkinsonian motor signs in all patients followed for 6 months. Levodopa equivalent daily intake was significantly reduced in the STN group. Changes in UPDRS, Hoehn _ Yahr and Schwab England ADL scores were similar in both groups. Cognitive functions were unchanged in both groups. Complications were observed in two patients: one had a left homonymous hemianopsia after pallidotomy and another one developed left hemiballistic movements 3 days after subthalamotomy which partly improved within 1 month with Valproate 1000 mg / day. The findings of this study suggest that lesions of the unilateral STN and GPi are equally effective treatment for patients with advanced PD refractory to medical treatment.

idiopathic Parkinson' s disease

idiopathic Parkinson' s disease

PD

dyskinesias

Parkinson' s Disease

parkinsonian

homonymous hemianopsia

PD

levodopa

levodopa

Levodopa

Valproate

levodopa

dyskinesias

levodopa

dyskinesias

Levodopa

dyskinesias


Input: Protective effects of antithrombin on puromycin aminonucleoside nephrosis in rats. We investigated the effects of antithrombin, a plasma inhibitor of coagulation factors, in rats with puromycin aminonucleoside - induced nephrosis, which is an experimental model of human nephrotic syndrome. Antithrombin (50 or 500 IU / kg / i. v.) was administered to rats once a day for 10 days immediately after the injection of puromycin aminonucleoside (50 mg / kg / i. v.). Treatment with antithrombin attenuated the puromycin aminonucleoside - induced hematological abnormalities. Puromycin aminonucleoside - induced renal dysfunction and hyperlipidemia were also suppressed. Histopathological examination revealed severe renal damage such as proteinaceous casts in tubuli and tubular expansion in the kidney of control rats, while an improvement of the damage was seen in antithrombin - treated rats. In addition, antithrombin treatment markedly suppressed puromycin aminonucleoside - induced apoptosis of renal tubular epithelial cells. Furthermore, puromycin aminonucleoside - induced increases in renal cytokine content were also decreased. These findings suggest that thrombin plays an important role in the pathogenesis of puromycin aminonucleoside - induced nephrotic syndrome. Treatment with antithrombin may be clinically effective in patients with nephrotic syndrome.

puromycin aminonucleoside

puromycin aminonucleoside

puromycin aminonucleoside

puromycin aminonucleoside

Puromycin aminonucleoside

puromycin aminonucleoside

puromycin aminonucleoside

puromycin aminonucleoside

nephrosis

nephrosis

nephrotic syndrome

hematological abnormalities

renal dysfunction

hyperlipidemia

renal damage

nephrotic syndrome

nephrotic syndrome

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

Puromycin aminonucleoside

nephrosis

Puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis


Input: Reverse or inverted left ventricular apical ballooning syndrome (reverse Takotsubo cardiomyopathy) in a young woman in the setting of amphetamine use. Transient left ventricular apical ballooning syndrome was first described in Japan as " Takotsubo cardiomyopathy. " This syndrome has been identified in many other countries. Many variations of this syndrome have been recently described in the literature. One of the rarest is the reverse type of this syndrome, with hyperdynamic apex and complete akinesia of the base (as opposed to the classic apical ballooning). In this article, we report an interesting case of a young woman who presented with this rare type of reverse apical ballooning syndrome occurring after amphetamine use. This report is followed by review of the literature.

left ventricular apical ballooning syndrome

Takotsubo cardiomyopathy

left ventricular apical ballooning syndrome

Takotsubo cardiomyopathy

akinesia

apical ballooning

apical ballooning syndrome

amphetamine

amphetamine

amphetamine

left ventricular apical ballooning syndrome

amphetamine

Takotsubo cardiomyopathy

amphetamine

left ventricular apical ballooning syndrome

amphetamine

Takotsubo cardiomyopathy

amphetamine

apical ballooning

amphetamine

apical ballooning syndrome

amphetamine

left ventricular apical ballooning syndrome

amphetamine

Takotsubo cardiomyopathy

amphetamine

left ventricular apical ballooning syndrome

amphetamine

Takotsubo cardiomyopathy

amphetamine

apical ballooning

amphetamine

apical ballooning syndrome


Input: Attenuated disruption of prepulse inhibition by dopaminergic stimulation after maternal deprivation and adolescent corticosterone treatment in rats. The development of schizophrenia may include an early neurodevelopmental stress component which increases vulnerability to later stressful life events, in combination leading to overt disease. We investigated the effect of an early stress, in the form of maternal deprivation, combined with a later stress, simulated by chronic periadolescent corticosterone treatment, on behaviour in rats. Acute treatment with apomorphine caused disruption of prepulse inhibition (PPI) in controls and in rats that had undergone either maternal deprivation or corticosterone treatment, but was surprisingly absent in rats that had undergone the combined early and late stress. Amphetamine treatment significantly disrupted PPI in both non - deprived groups, but was absent in both maternally deprived groups. The serotonin - 1A receptor agonist, 8 - OH - DPAT, induced a significant disruption of PPI in all groups. Amphetamine - induced locomotor hyperactivity was similar in all groups. These results show an inhibitory interaction of early stress, caused by maternal deprivation, combined with' adolescent' stress, simulated by corticosterone treatment, on dopaminergic regulation of PPI. The altered effects of apomorphine and amphetamine could indicate differential changes in dopamine receptor signalling leading to functional desensitisation, or altered modulation of sensory gating in the nucleus accumbens by limbic structures such as the hippocampus.

corticosterone

corticosterone

apomorphine

corticosterone

Amphetamine

serotonin

8 - OH - DPAT

Amphetamine

corticosterone

apomorphine

amphetamine

dopamine

schizophrenia

locomotor hyperactivity

Amphetamine

locomotor hyperactivity

Amphetamine

locomotor hyperactivity

amphetamine

locomotor hyperactivity


Input: Peripheral iron dextran induced degeneration of dopaminergic neurons in rat substantia nigra. Iron accumulation is considered to be involved in the pathogenesis of Parkinson' s disease. To demonstrate the relationship between peripheral iron overload and dopaminergic neuron loss in rat substantia nigra (SN), in the present study we used fast cyclic voltammetry, tyrosine hydroxylase (TH) immunohistochemistry, Perls' iron staining, and high performance liquid chromatography - electrochemical detection to study the degeneration of dopaminergic neurons and increased iron content in the SN of iron dextran overloaded animals. The findings showed that peripheral iron dextran overload increased the iron staining positive cells and reduced the number of TH - immunoreactive neurons in the SN. As a result, dopamine release and content, as well as its metabolites contents were decreased in caudate putamen. Even more dramatic changes were found in chronic overload group. These results suggest that peripheral iron dextran can increase the iron level in the SN, where excessive iron causes the degeneration of dopaminergic neurons. The chronic iron overload may be more destructive to dopaminergic neurons than the acute iron overload.

iron dextran

Iron

iron

tyrosine

iron

iron

iron dextran

iron dextran

iron

dopamine

iron dextran

iron

iron

iron

iron

degeneration of dopaminergic neurons

Parkinson' s disease

degeneration of dopaminergic neurons

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons

iron dextran

degeneration of dopaminergic neurons


Input: Warfarin - induced leukocytoclastic vasculitis. Skin reactions associated with oral coumarin - derived anticoagulants are an uncommon occurrence. Leukocytoclastic vasculitis (LV) is primarily a cutaneous small vessel vasculitis, though systemic involvement may be encountered. We report 4 patients with late - onset LV probably due to warfarin. All 4 patients presented with skin eruptions that developed after receiving warfarin for several years. The results of skin lesion biopsies were available in 3 patients, confirming LV Cutaneous lesions resolved in all patients after warfarin was discontinued. In 2 of the 4 patients, rechallenge with warfarin led to recurrence of the lesions. LV may be a late - onset adverse reaction associated with warfarin therapy.

Warfarin

coumarin

warfarin

warfarin

warfarin

warfarin

warfarin

leukocytoclastic vasculitis

Leukocytoclastic vasculitis

LV

cutaneous small vessel vasculitis

LV

skin eruptions

skin lesion

LV Cutaneous lesions

LV

Warfarin

LV Cutaneous lesions

warfarin

LV Cutaneous lesions

warfarin

LV Cutaneous lesions

warfarin

LV Cutaneous lesions

warfarin

LV Cutaneous lesions

warfarin

LV Cutaneous lesions


Input: The activation of spinal N - methyl - D - aspartate receptors may contribute to degeneration of spinal motor neurons induced by neuraxial morphine after a noninjurious interval of spinal cord ischemia. We investigated the relationship between the degeneration of spinal motor neurons and activation of N - methyl - d - aspartate (NMDA) receptors after neuraxial morphine following a noninjurious interval of aortic occlusion in rats. Spinal cord ischemia was induced by aortic occlusion for 6 min with a balloon catheter. In a microdialysis study, 10 muL of saline (group C; n = 8) or 30 mug of morphine (group M; n = 8) was injected intrathecally (IT) 0. 5 h after reflow, and 30 mug of morphine (group SM; n = 8) or 10 muL of saline (group SC; n = 8) was injected IT 0. 5 h after sham operation. Microdialysis samples were collected preischemia, before IT injection, and at 2, 4, 8, 24, and 48 h of reperfusion (after IT injection). Second, we investigated the effect of IT MK - 801 (30 mug) on the histopathologic changes in the spinal cord after morphine - induced spastic paraparesis. After IT morphine, the cerebrospinal fluid (CSF) glutamate concentration was increased in group M relative to both baseline and group C (P < 0. 05). This increase persisted for 8 hrs. IT MK - 801 significantly reduced the number of dark - stained alpha - motoneurons after morphine - induced spastic paraparesis compared with the saline group. These data indicate that IT morphine induces spastic paraparesis with a concomitant increase in CSF glutamate, which is involved in NMDA receptor activation. We suggest that opioids may be neurotoxic in the setting of spinal cord ischemia via NMDA receptor activation.

N - methyl - D - aspartate

morphine

N - methyl - d - aspartate

NMDA

morphine

morphine

morphine

MK - 801

morphine

morphine

glutamate

MK - 801

morphine

morphine

glutamate

NMDA

NMDA

spinal cord ischemia

aortic occlusion

Spinal cord ischemia

aortic occlusion

spastic paraparesis

spastic paraparesis

spastic paraparesis

neurotoxic

spinal cord ischemia

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis

morphine

spastic paraparesis


Input: Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel beta 2 - subunits. Sodium channel beta - subunits modulate channel gating, assembly, and cell surface expression in heterologous cell systems. We generated beta2 (- / -) mice to investigate the role of beta2 in control of sodium channel density, localization, and function in neurons in vivo. Measurements of [(3) H] saxitoxin (STX) binding showed a significant reduction in the level of plasma membrane sodium channels in beta2 (- / -) neurons. The loss of beta2 resulted in negative shifts in the voltage dependence of inactivation as well as significant decreases in sodium current density in acutely dissociated hippocampal neurons. The integral of the compound action potential in optic nerve was significantly reduced, and the threshold for action potential generation was increased, indicating a reduction in the level of functional plasma membrane sodium channels. In contrast, the conduction velocity, the number and size of axons in the optic nerve, and the specific localization of Na (v) 1. 6 channels in the nodes of Ranvier were unchanged. beta2 (- / -) mice displayed increased susceptibility to seizures, as indicated by reduced latency and threshold for pilocarpine - induced seizures, but seemed normal in other neurological tests. Our observations show that beta2 - subunits play an important role in the regulation of sodium channel density and function in neurons in vivo and are required for normal action potential generation and control of excitability.

sodium

sodium

Sodium

sodium

saxitoxin

STX

sodium

sodium

sodium

pilocarpine

sodium

seizures

seizures

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures


Input: Screening for stimulant use in adult emergency department seizure patients. OBJECTIVE: The objective of this study was to determine the prevalence of positive plasma drug screening for cocaine or amphetamine in adult emergency department seizure patients. METHODS: This prospective study evaluated consecutive eligible seizure patients who had a plasma sample collected as part of their clinical evaluation. Plasma was tested for amphetamine and the cocaine metabolite benzoylecgonine using enzyme - mediated immunoassay methodology. Plasma samples with benzoylecgonine greater than 150 ng / mL or an amphetamine greater than 500 ng / mL were defined as positive. Patient demographics, history of underlying drug or alcohol - related seizure disorder, estimated time from seizure to sample collection, history or suspicion of cocaine or amphetamine abuse, results of clinical urine testing for drugs of abuse, and assay results were recorded without patient identifiers. RESULTS: Fourteen of 248 (5. 6%, 95% CI 2. 7% - 8. 5%) plasma samples were positive by immunoassay testing for benzoylecgonine and no samples (0%, 95% CI 0 - 1. 2%) were positive for amphetamine. Positive test results were more common in patient visits where there was a history or suspicion of cocaine or amphetamine abuse (p < 0. 0005). CONCLUSIONS: During this study period, routine plasma screening for cocaine and amphetamines in adult seizure patients had a low yield. As a result, routine plasma screening would yield few cases of stimulant drug in which there was neither a history nor suspicion of drug abuse in this population.

seizure

seizure

seizure

seizure

seizure

cocaine or amphetamine abuse

cocaine or amphetamine abuse

amphetamine abuse

cocaine or amphetamine abuse

cocaine or amphetamine abuse

amphetamine abuse

seizure

drug abuse

cocaine

amphetamine

amphetamine

cocaine

benzoylecgonine

benzoylecgonine

amphetamine

alcohol

benzoylecgonine

amphetamine

cocaine

amphetamines

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure

benzoylecgonine

seizure


Input: Evidence of functional somatotopy in GPi from results of pallidotomy. The objective of this study was to explore the functional anatomy of the globus pallidus internus (GPi) by studying the effects of unilateral pallidotomy on parkinsonian' off' signs and levodopa - induced dyskinesias (LID). We found significant positive correlations between the preoperative levodopa responsiveness of motor signs and the levodopa responsiveness of scores in timed tests (Core Assessment Program for Intracerebral Transplantations) in the contralateral limbs and the improvement in these scores after surgery, whereas there was no correlation with the improvement in LID. We also found a highly significant correlation (P: < 0. 0001, r = 0. 8) between the volume of the ventral lesion in the GPi and the improvement in LID in the contralateral limbs, whereas there was no correlation between the ventral volume and the improvement in parkinsonian' off' signs. The volumes of the total lesion cylinder and the dorsal lesion did not correlate with the outcome of either dyskinesias or parkinsonian' off' signs. The differential predictive value of levodopa responsiveness for the outcome of parkinsonian' off' signs and LID and the different correlations of ventral lesion volume with dyskinesias and parkinsonian' off' signs indicate that different anatomical or pathophysiological substrates may be responsible for the generation of parkinsonian' off' signs and dyskinesias. Whereas cells in a wider area of the GPi may be implicated in parkinsonism, the ventral GPi seems to be crucial for the manifestation of LID. We suggest that our observations are additional proof of the functional somatotopy of the systems within the GPi that mediate parkinsonism and dyskinesias, especially along the dorsoventral trajectory used in pallidotomy. The outcome of pallidotomy in which the lesion involves the ventral and dorsal GPi could be the net effect of alteration in the activity of pathways which mediate different symptoms, and hence could be variable.

parkinsonian

dyskinesias

LID

LID

LID

parkinsonian

dyskinesias

parkinsonian

parkinsonian

LID

dyskinesias

parkinsonian

parkinsonian

dyskinesias

parkinsonism

LID

parkinsonism

dyskinesias

levodopa

levodopa

levodopa

levodopa

levodopa

dyskinesias

levodopa

LID

levodopa

LID

levodopa

LID

levodopa

dyskinesias

levodopa

LID

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LID

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LID

levodopa

LID

levodopa

LID

levodopa

dyskinesias

levodopa

LID

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LID

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LID

levodopa

LID

levodopa

LID

levodopa

dyskinesias

levodopa

LID

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LID

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LID

levodopa

LID

levodopa

LID

levodopa

dyskinesias

levodopa

LID

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LID

levodopa

dyskinesias


Input: Pain responses in methadone - maintained opioid abusers. Providing pain management for known opioid abusers is a challenging clinical task, in part because little is known about their pain experience and analgesic requirements. This study was designed to describe pain tolerance and analgesic response in a sample of opioid addicts stabilized in methadone - maintenance (MM) treatment (n = 60) in comparison to matched nondependent control subjects (n = 60). By using a placebo - controlled, two - way factorial design, tolerance to cold - pressor (CP) pain was examined, both before and after oral administration of therapeutic doses of common opioid (hydromorphone 2 mg) and nonsteroidal anti - inflammatory (ketorolac 10 mg) analgesic agents. Results showed that MM individuals were significantly less tolerant of CP pain than control subjects, replicating previous work. Analgesic effects were significant neither for medication nor group. These data indicate that MM opioid abusers represent a pain - intolerant subset of clinical patients. Their complaints of pain should be evaluated seriously and managed aggressively.

Pain

pain

pain

pain

opioid addicts

pain

pain

pain - intolerant

pain

methadone

methadone

hydromorphone

ketorolac

methadone

pain - intolerant

methadone

pain - intolerant


Input: Urine N - acetyl - beta - D - glucosaminidase - - a marker of tubular damage? BACKGROUND: Although an indicator of renal tubular dysfunction, an increased urinary N - acetyl - beta - D - glucosaminidase (NAG) activity might reflect increased lysosomal activity in renal tubular cells. METHODS: Puromycin aminonucleoside (PAN) was administered to Sprague Dawley rats to induce proteinuria. Total protein, albumin, NAG activity and protein electrophoretic pattern were assessed in daily urine samples for 33 days. The morphological appearance of the kidneys was examined on days three, four, six, eight and thirty three and the NAG isoenzyme patterns on days zero, four, eight and thirty three. RESULTS: Following intravenous PAN urine volume and urine NAG activity increased significantly by day two, but returned to normal by day four. After day four all treated animals exhibited a marked rise in urine albumin, total protein excretion and NAG activity. Electrophoresis showed a generalised increase in middle and high molecular weight urine proteins from day four onwards. Protein droplets first appeared prominent in tubular cells on day four. Peak urine NAG activity and a change in NAG isoenzyme pattern coincided with both the peak proteinuria and the reduction in intracellular protein and NAG droplets (day six onwards). CONCLUSIONS: This animal model demonstrates that an increase in lysosomal turnover and hence urine NAG activity, occurs when increased protein is presented to the tubular cells. Urine NAG activity is thus a measure of altered function in the renal tubules and not simply an indicator of damage.

renal tubular dysfunction

proteinuria

proteinuria

Puromycin aminonucleoside

PAN

PAN

Puromycin aminonucleoside

proteinuria

Puromycin aminonucleoside

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria


Input: Over expression of vascular endothelial growth factor and its receptor during the development of estrogen - induced rat pituitary tumors may mediate estrogen - initiated tumor angiogenesis. Estrogens, which have been associated with several types of human and animal cancers, can induce tumor angiogenesis in the pituitary of Fischer 344 rats. The mechanistic details of tumor angiogenesis induction, during estrogen carcinogenesis, are still unknown. To elucidate the role of estrogen in the regulation of tumor angiogenesis in the pituitary of female rats, the density of blood vessels was analysed using factor VIII related antigen (FVIIIRAg) immunohistochemistry and the expression of vascular endothelial growth factor / vascular permeability factor (VEGF / VPF) was examined by Western blot and immunohistochemical analysis. The expression of VEGF receptor (VEGFR - 2 / Flk - 1 / KDR) was also examined by immunohistochemistry. The results demonstrated that 17beta - estradiol (E2) induces neovascularization, as well as the growth and enlargement of blood vessels after 7 days of exposure. The high tumor angiogenic potential was associated with an elevated VEGF / VPF protein expression in the E2 exposed pituitary of ovariectomized (OVEX) rats. VEGF / VPF and FVIIIRAg immunohistochemistry and endothelial specific lectin (UEA1) binding studies, indicate that the elevation of VEGF protein expression initially occurred in both blood vessels and non - endothelial cells. After 15 days of E2 exposure, VEGF / VPF protein expression, in the non - endothelial cell population, sharply declined and was restricted to the blood vessels. The function of non - endothelial - derived VEGF is not clear. Furthermore, immunohistochemical studies demonstrated that VEGFR - 2 (flk - 1 / KDR), expression was elevated significantly in the endothelial cells of microblood vessels after 7 days of E2 exposure. These findings suggest that over expression of VEGF and its receptor (VEGFR - 2) may play an important role in the initial step of the regulation of estrogen induced tumor angiogenesis in the rat pituitary.

estrogen

estrogen

Estrogens

estrogen

estrogen

17beta - estradiol

estrogen

pituitary tumors

tumor

cancers

tumor

tumor

carcinogenesis

tumor

tumor

tumor

17beta - estradiol

pituitary tumors

pituitary tumors

pituitary tumors

pituitary tumors

pituitary tumors


Input: Pravastatin - associated myopathy. Report of a case. A case of acute inflammatory myopathy associated with the use of pravastatin, a new hydrophilic 3 - hydroxy - 3 methylglutaril coenzyme A reductase inhibitor, is reported. The patient, a 69 - year - old man was affected by non - insulin - dependent diabetes mellitus and hypertension. He assumed pravastatin (20 mg / day) because of hypercholesterolemia. He was admitted with acute myopathy of the lower limbs which resolved in a few days after pravastatin discontinuation. A previously unknown hypothyroidism, probably due to chronic autoimmune thyroiditis, was evidenced. Muscle biopsy (left gastrocnemius) revealed a perimysial and endomysial inflammatory infiltrate with a prevalence of CD4 + lymphocytes. While lovastatin and simvastatin have been associated with toxic myopathy, pravastatin - associated myopathy could represent a distinct, inflammatory entity.

Pravastatin

pravastatin

pravastatin

pravastatin

lovastatin

simvastatin

pravastatin

myopathy

inflammatory myopathy

non - insulin - dependent diabetes mellitus

hypertension

hypercholesterolemia

myopathy

hypothyroidism

autoimmune thyroiditis

myopathy

myopathy

Pravastatin

inflammatory myopathy

pravastatin

inflammatory myopathy

pravastatin

inflammatory myopathy

pravastatin

inflammatory myopathy

pravastatin

inflammatory myopathy


Input: Dose - effect and structure - function relationships in doxorubicin cardiomyopathy. The cardiomyopathy (CM) produced by the anticancer drug doxorubicin (DXR) (Adriamycin) provides a unique opportunity to analyze dose - effect and structure - function relationships during development of myocardial disease. We measured the degree of morphologic damage by ultrastructural examination of endomyocardial biopsy and the degree of performance abnormally by right heart catheterization in patients receiving DXR. Morphologic damage was variable but was proportional to the total cumulative DXR dose between 100 and 600 mg / m2. Performance abnormalities correlated weakly with dose, exhibited a curvilinear relationship, and had a " threshold " for expression. Catheterization abnormalities correlated well with morphologic damage (r = 0. 57 to 0. 78) in a subgroup of patients in whom exercise hemodynamics were measured, and this relationship also exhibited a curvilinear, threshold configuration. In DXR - CM myocardial damage is proportional to the degree of cytotoxic insult (DXR dose) while myocardial function is preserved until a critical dose or degree of damage is reached, after which myocardial performance deteriorates rapidly.

doxorubicin

doxorubicin

DXR

Adriamycin

DXR

DXR

DXR

DXR

cardiomyopathy

cardiomyopathy

CM

myocardial disease

CM

myocardial damage

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

CM

doxorubicin

myocardial disease

doxorubicin

CM

doxorubicin

myocardial damage

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

CM

doxorubicin

myocardial disease

doxorubicin

CM

doxorubicin

myocardial damage

DXR

cardiomyopathy

DXR

cardiomyopathy

DXR

CM

DXR

myocardial disease

DXR

CM

DXR

myocardial damage

Adriamycin

cardiomyopathy

Adriamycin

cardiomyopathy

Adriamycin

CM

Adriamycin

myocardial disease

Adriamycin

CM

Adriamycin

myocardial damage

DXR

cardiomyopathy

DXR

cardiomyopathy

DXR

CM

DXR

myocardial disease

DXR

CM

DXR

myocardial damage

DXR

cardiomyopathy

DXR

cardiomyopathy

DXR

CM

DXR

myocardial disease

DXR

CM

DXR

myocardial damage

DXR

cardiomyopathy

DXR

cardiomyopathy

DXR

CM

DXR

myocardial disease

DXR

CM

DXR

myocardial damage

DXR

cardiomyopathy

DXR

cardiomyopathy

DXR

CM

DXR

myocardial disease

DXR

CM

DXR

myocardial damage


Input: Fatal aplastic anemia following topical administration of ophthalmic chloramphenicol. A 73 - year - old woman died of aplastic anemia less than two months after undergoing cataract extraction and beginning topical therapy with chloramphenicol. The first signs of pancytopenia began within one month of the surgery. The pattern of the aplastic anemia was associated with an idiosyncratic response to chloramphenicol. This was the second report of fatal aplastic anemia after topical treatment with chloramphenicol for ocular conditions, although two cases of reversible bone marrow hypoplasia have also been reported. Any other suspected cases of ocular toxicity associated with topically applied chloramphenicol should be reported to the National Registry of Drug - Induced Ocular Side Effects, Oregon Health Sciences University, Portland, OR 97201.

aplastic anemia

aplastic anemia

cataract

pancytopenia

aplastic anemia

aplastic anemia

bone marrow hypoplasia

ocular toxicity

chloramphenicol

chloramphenicol

chloramphenicol

chloramphenicol

chloramphenicol

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia

chloramphenicol

aplastic anemia


Input: Bradycardia due to trihexyphenidyl hydrochloride. A chronic schizophrenic patient was treated with an anticholinergic drug, trihexyphenidyl hydrochloride. The patient developed, paradoxically, sinus bradycardia. The reaction was specific to trihexyphenidyl and not to other anticholinergic drugs. This antidyskinetic drug is widely used in clinical psychiatric practice and physicians should be aware of this side effect.

Bradycardia

schizophrenic

bradycardia

psychiatric

trihexyphenidyl hydrochloride

trihexyphenidyl hydrochloride

trihexyphenidyl

trihexyphenidyl hydrochloride

Bradycardia

trihexyphenidyl hydrochloride

bradycardia

trihexyphenidyl hydrochloride

Bradycardia

trihexyphenidyl hydrochloride

bradycardia

trihexyphenidyl

Bradycardia

trihexyphenidyl

bradycardia


Input: Experimental cyclosporine nephrotoxicity: risk of concomitant chemotherapy. The role of cyclosporine (CSA) alone or in combination with various chemotherapeutics in the development of renal toxicity was evaluated in rats. Administration of 20 mg / kg / day CSA for 4 weeks caused renal functional and structural changes similar to those reported in man. The combined administration of CSA and various chemotherapeutic drugs with a nephrotoxic potential, such as gentamicin (at therapeutic doses), amphothericin B and ketoconazole, which are frequently used in immunosuppressed patients, did not aggravate the CSA induced toxicity in the rat model. Gentamicin at toxic doses, however, increased CSA nephrotoxicity. Thus, the nephrotoxicity induced by CSA has a different pathogenetic mechanism.

cyclosporine

cyclosporine

CSA

CSA

CSA

gentamicin

amphothericin B

ketoconazole

CSA

Gentamicin

CSA

CSA

nephrotoxicity

renal toxicity

nephrotoxic

toxicity

nephrotoxicity

nephrotoxicity

cyclosporine

nephrotoxicity

cyclosporine

renal toxicity

cyclosporine

nephrotoxic

cyclosporine

nephrotoxicity

cyclosporine

nephrotoxicity

cyclosporine

nephrotoxicity

cyclosporine

renal toxicity

cyclosporine

nephrotoxic

cyclosporine

nephrotoxicity

cyclosporine

nephrotoxicity

CSA

nephrotoxicity

CSA

renal toxicity

CSA

nephrotoxic

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

renal toxicity

CSA

nephrotoxic

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

renal toxicity

CSA

nephrotoxic

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

renal toxicity

CSA

nephrotoxic

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

renal toxicity

CSA

nephrotoxic

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

nephrotoxicity

CSA

renal toxicity

CSA

nephrotoxic

CSA

nephrotoxicity

CSA

nephrotoxicity


Input: Receptor mechanisms of nicotine - induced locomotor hyperactivity in chronic nicotine - treated rats. Rats were pretreated with saline or nicotine (1. 5 mg / kg per day) by subcutaneously implanting each animal with an Alzet osmotic mini - pump which continuously released saline or nicotine for 1, 5 and 14 days. At the end of each pretreatment period, animals were used for (i) determining their locomotor response to acutely injected nicotine (0. 2 mg / kg, s. c.) and (ii) measuring the density of L - [3H] nicotine and [3H] spiperone binding sites in the striatum. We observed no changes in nicotine - induced locomotor response, striatal L - [3H] nicotine and [3H] spiperone binding in the animals pretreated with nicotine for 1 day. In rats which were pretreated with nicotine for 5 days, there was a significant increase in the nicotine - stimulated locomotor response which was associated with an increase in the number of L - [3H] nicotine binding sites and also with an elevated dopamine (DA) level in the striatum. The number of striatal [3H] spiperone binding sites was not affected. In animals pretreated with nicotine for 14 days, the nicotine - induced locomotor response remained to be potentiated. However, this response was correlated with an elevated number of striatal [3H] spiperone binding sites, whereas the number of striatal L - [3H] nicotine binding sites and the striatal DA level were normal. These results suggest that chronic nicotine - treated rats develop locomotor hyperactivity in response to nicotine initially due to increases of both the density of nicotinic receptors and DA concentration, followed by inducing DA receptor supersensitivity in the striatum.

nicotine

nicotine

nicotine

nicotine

nicotine

nicotine

spiperone

nicotine

nicotine

spiperone

nicotine

nicotine

nicotine

nicotine

dopamine

DA

spiperone

nicotine

nicotine

spiperone

nicotine

DA

nicotine

nicotine

DA

DA

locomotor hyperactivity

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity

nicotine

locomotor hyperactivity