Instruction: Extract chemical and disease entities from the following text.

Input: Renal Fanconi syndrome and myopathy after liver transplantation: drug-related mitochondrial cytopathy? Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.

Output: Chemical/Disease Entities: Renal Fanconi syndrome (Disease), myopathy (Disease), mitochondrial cytopathy (Disease), Wilson's disease (Disease), Tacrolimus (Chemical), MMF (Chemical), steroids (Chemical), Lamivudine (Chemical), hepatitis B infection (Disease), renal Fanconi syndrome (Disease), metabolic acidosis (Disease), hypophosphatemia (Disease), glycosuria (Disease), aminoaciduria (Disease), tacrolimus (Chemical), acidosis (Disease), sirolimus (Chemical), acidosis (Disease), muscle weakness (Disease), Fanconi syndrome (Disease), myopathy (Disease), mitochondrial disorders (Disease), tubular dysfunction (Disease), myopathy (Disease), mitochondrial dysfunction (Disease), tacrolimus (Chemical), lamivudine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Antipsychotic-like profile of thioperamide, a selective H3-receptor antagonist in mice. Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.

Output: Chemical/Disease Entities: thioperamide (Chemical), schizophrenia (Disease), histamine (Chemical), catalepsy (Disease), apomorphine (Chemical), amphetamine (Chemical), Catalepsy (Disease), haloperidol (Chemical), apomorphine (Chemical), amphetamine (Chemical), (R)-alpha-methylhistamine (Chemical), RAMH (Chemical), thioperamide (Chemical), THP (Chemical), catalepsy (Disease), THP (Chemical), haloperidol (Chemical), catalepsy (Disease), RAMH (Chemical), THP (Chemical), RAMH (Chemical), THP (Chemical), amphetamine (Chemical), hyperactivity (Disease), THP (Chemical), RAMH (Chemical), THP (Chemical), apomorphine (Chemical), THP (Chemical), RAMH (Chemical), THP (Chemical), haloperidol (Chemical), catalepsy (Disease), amphetamine (Chemical), hyperactivity (Disease), apomorphine (Chemical), THP (Chemical), RAMH (Chemical), histamine (Chemical), schizophrenia (Disease)


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Input: Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in a young woman with Ebstein's anomaly. In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.

Output: Chemical/Disease Entities: platypnea-orthodeoxia-like syndrome (Disease), propafenone (Chemical), overdose (Disease), Ebstein's anomaly (Disease), Ebstein's anomaly (Disease), platypnea-orthodeoxia (Disease), hypoxia (Disease), cyanosis (Disease), patent foramen ovale (Disease), propafenone (Chemical), overdose (Disease), biventricular dysfunction (Disease), hypotension (Disease)


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Input: A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188). BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.

Output: Chemical/Disease Entities: cisplatin (Chemical), WR-2721 (Chemical), amifostine (Chemical), breast carcinoma (Disease), Cisplatin (Chemical), breast carcinoma (Disease), cisplatin (Chemical), cisplatin (Chemical), toxicities (Disease), cisplatin (Chemical), nephrotoxicity (Disease), ototoxicity (Disease), neurotoxicity (Disease), breast carcinoma (Disease), WR-2721 (Chemical), amifostine (Chemical), Amifostine (Chemical), alkylating agents (Chemical), cisplatin (Chemical), cisplatin (Chemical), amifostine (Chemical), cisplatin (Chemical), nephrotoxicity (Disease), ototoxicity (Disease), neuropathy (Disease), cisplatin (Chemical), amifostine (Chemical), breast carcinoma (Disease), amifostine (Chemical), amifostine (Chemical), cisplatin (Chemical), mannitol (Chemical), cisplatin (Chemical), Neurologic toxicity (Disease), toxicities (Disease), cisplatin (Chemical), amifostine (Chemical), tumor (Disease), toxicity (Disease), amifostine (Chemical), cisplatin (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Warfarin-induced iliopsoas hemorrhage with subsequent femoral nerve palsy. We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.

Output: Chemical/Disease Entities: Warfarin (Chemical), hemorrhage (Disease), femoral nerve palsy (Disease), warfarin (Chemical), muscle tear (Disease), pain (Disease), contracture (Disease), hematoma (Disease), nerve entrapment (Disease), femoral nerve palsy (Disease), partial loss of quadriceps functions (Disease), femoral nerve palsy (Disease), warfarin (Chemical), peripheral neuropathy (Disease), pain (Disease), motor and sensory impairment (Disease), contracture (Disease)


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Input: Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis. We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process.

Output: Chemical/Disease Entities: Myasthenia gravis (Disease), penicillamine (Chemical), chloroquine (Chemical), rheumatoid arthritis (Disease), myasthenia gravis (Disease), penicillamine (Chemical), chloroquine (Chemical), rheumatoid arthritis (Disease), acetylcholine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Nephrotoxicity of combined cephalothin-gentamicin regimen. Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.

Output: Chemical/Disease Entities: Nephrotoxicity (Disease), cephalothin (Chemical), gentamicin (Chemical), acute tubular necrosis (Disease), cephalothin sodium (Chemical), gentamicin sulfate (Chemical), nephrotoxicity (Disease), renal insufficiency (Disease)


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Input: Components of lemon essential oil attenuate dementia induced by scopolamine. The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.

Output: Chemical/Disease Entities: dementia (Disease), scopolamine (Chemical), dementia (Disease), s-limonene (Chemical), s-perillyl alcohol (Chemical), memory impaired (Disease), scopolamine (Chemical), s-perillyl alcohol (Chemical), deficit of associative memory (Disease), dopamine (Chemical), scopolamine (Chemical), s-limonene (Chemical), s-perillyl alcohol (Chemical), scopolamine (Chemical)


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Input: The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat. Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.

Output: Chemical/Disease Entities: Ro4368554 (Chemical), memory deficiency (Disease), serotonin (Chemical), 5-HT (Chemical), acetylcholine (Chemical), ACh (Chemical), 5-HT (Chemical), Ro4368554 (Chemical), 3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole (Chemical), scopolamine (Chemical), tryptophan (Chemical), TRP (Chemical), metrifonate (Chemical), metrifonate (Chemical), Ro4368554 (Chemical), Ro4368554 (Chemical), metrifonate (Chemical), memory deficits (Disease), scopolamine (Chemical), TRP (Chemical), Ro4368554 (Chemical), memory deficit (Disease), Ro4368554 (Chemical), 5-HT (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Lone atrial fibrillation associated with creatine monohydrate supplementation. Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.

Output: Chemical/Disease Entities: atrial fibrillation (Disease), creatine (Chemical), Atrial fibrillation (Disease), heart disease (Disease), arrhythmia (Disease), Thyroid disorders (Disease), acute alcohol intoxication (Disease), atrial fibrillation (Disease), fractures (Disease), magnesium (Chemical), potassium (Chemical), alcohol (Chemical), creatine (Chemical), heparin (Chemical), diltiazem (Chemical), amiodarone (Chemical), metoprolol (Chemical), aspirin (Chemical), creatine (Chemical), creatine (Chemical), creatine (Chemical), arrhythmia (Disease)


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Input: Comparison of developmental toxicity of selective and non-selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats--DFU and piroxicam study. BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.

Output: Chemical/Disease Entities: toxicity (Disease), DFU (Chemical), piroxicam (Chemical), toxicity (Disease), toxicity (Disease), piroxicam (Chemical), DFU (Chemical), 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon (Chemical), piroxicam (Chemical), DFU (Chemical), piroxicam (Chemical), toxicity (Disease), intrauterine growth retardation (Disease), increase of external and skeletal variations (Disease), piroxicam (Chemical), DFU (Chemical), toxicity (Disease), piroxicam (Chemical), DFU (Chemical), DFU (Chemical), piroxicam (Chemical)


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Input: Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice. Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.

Output: Chemical/Disease Entities: steroids (Chemical), cocaine (Chemical), seizures (Disease), steroids (Chemical), seizures (Disease), drug dependence (Disease), steroid (Chemical), gamma-aminobutyric acid (Chemical), GABA (Chemical), cocaine (Chemical), cocaine (Chemical), seizure (Disease), Allopregnanolone (Chemical), 3alpha-hydroxy-5alpha-pregnan-20-one (Chemical), pregnanolone (Chemical), 3alpha-hydroxy-5beta-pregnan-20-one (Chemical), ganaxolone (Chemical), allopregnanolone (Chemical), 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one (Chemical), cocaine (Chemical), seizures (Disease), seizures (Disease), cocaine (Chemical), GABA (Chemical), seizures (Disease), allopregnanolone (Chemical), ganaxolone (Chemical), Allopregnanolone (Chemical), pregnanolone (Chemical), ganaxolone (Chemical), steroids (Chemical), cocaine (Chemical)


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Input: Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat. BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.

Output: Chemical/Disease Entities: cyclosporine A (Chemical), tacrolimus (Chemical), sirolimus (Chemical), Sirolimus (Chemical), SRL (Chemical), nephrotoxic (Disease), SRL (Chemical), nephrotoxic (Disease), SRL (Chemical), nephrotoxic (Disease), cyclosporine A (Chemical), CsA (Chemical), tacrolimus (Chemical), FK506 (Chemical), SRL (Chemical), CsA (Chemical), FK506 (Chemical), SRL (Chemical), fibrosis (Disease), fibrosis (Disease), fibrosis (Disease), CsA (Chemical), FK506 (Chemical), SRL (Chemical), CsA (Chemical), FK506 (Chemical), SRL (Chemical), FK506 (Chemical), SRL (Chemical), CsA (Chemical), SRL (Chemical), fibrosis (Disease), FK506 (Chemical), SRL (Chemical), fibrosis (Disease), nephrotoxic (Disease), CsA (Chemical), SRL (Chemical), FK506 (Chemical), SRL (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats. Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.

Output: Chemical/Disease Entities: fucoidan (Chemical), intracerebral hemorrhage (Disease), brain damage (Disease), ischemic stroke (Disease), Intracerebral hemorrhage (Disease), inflammation (Disease), ischemic stroke (Disease), fucoidan (Chemical), brain damage (Disease), intracerebral hemorrhage (Disease), fucoidan (Chemical), hematoma (Disease), Fucoidan (Chemical), impaired blood clotting (Disease), hemodilution (Disease), hematomas (Disease), inflammation (Disease), hematoma (Disease), hemorrhage (Disease), white matter edema (Disease), neuronal loss (Disease), hematoma (Disease), intracerebral hemorrhage (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Paracetamol-associated coma, metabolic acidosis, renal and hepatic failure. A case of metabolic acidosis, acute renal failure and hepatic failure following paracetamol ingestion is presented. The diagnostic difficulty at presentation is highlighted. Continuous arteriovenous haemofiltration proved a valuable means of maintaining fluid and electrolyte balance. The patient recovered.

Output: Chemical/Disease Entities: Paracetamol (Chemical), coma (Disease), metabolic acidosis (Disease), metabolic acidosis (Disease), paracetamol (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Hepatic reactions associated with ketoconazole in the United Kingdom. Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.

Output: Chemical/Disease Entities: ketoconazole (Chemical), Ketoconazole (Chemical), hepatotoxicity (Disease), deaths (Disease), deaths (Disease), hepatotoxicity (Disease), jaundice (Disease), hepatocellular injury (Disease), cholestasis (Disease), rash (Disease), eosinophilia (Disease), Hepatitis (Disease), deaths (Disease), ketoconazole (Chemical), jaundice (Disease), hepatitis (Disease), hepatitis (Disease), ketoconazole (Chemical), hepatic injury (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Combined effects of prolonged prostaglandin E1-induced hypotension and haemodilution on human hepatic function. Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.

Output: Chemical/Disease Entities: prostaglandin E1 (Chemical), hypotension (Disease), haemodilution (Disease), prostaglandin E1 (Chemical), PGE1 (Chemical), hypotension (Disease), haemodilution (Disease), hypotension (Disease), haemodilution (Disease), hypotension (Disease), haemodilution (Disease), Haemodilution (Disease), dextran (Chemical), hypotension (Disease), PGE1 (Chemical), aceto-acetate (Chemical), 3-hydroxybutyrate (Chemical), hypotension (Disease), bilirubin (Chemical), PGE1 (Chemical), hypotension (Disease), haemodilution (Disease), impairment of hepatic function (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap. Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.

Output: Chemical/Disease Entities: Levodopa (Chemical), dyskinesias (Disease), Parkinson's disease (Disease), Levodopa (Chemical), Parkinson's disease (Disease), dopamine (Chemical), dyskinesias (Disease), levodopa (Chemical), dyskinesias (Disease), Parkinson's disease (Disease), dyskinetic movements (Disease), dopamine (Chemical), glutamate (Chemical), levodopa (Chemical), dyskinesias (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy. In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.

Output: Chemical/Disease Entities: seizures (Disease), epilepsy (Disease), epilepsy (Disease), pilocarpine (Chemical), status epilepticus (Disease), SE (Disease), Spontaneous recurrent seizures (Disease), SRS (Disease), seizure (Disease), epileptic (Disease), SRS (Disease), epileptic (Disease), seizures (Disease), epileptic (Disease), seizures (Disease), epileptic (Disease), epileptic (Disease), epileptic (Disease), seizures (Disease), neuronal loss (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.

Output: Chemical/Disease Entities: salvianolic acid A (Chemical), isoproterenol (Chemical), myocardial infarction (Disease), salvianolic acid A (Chemical), isoproterenol (Chemical), myocardial infarction (Disease), Isoproterenol (Chemical), lactate (Chemical), aspartate (Chemical), creatine (Chemical), malondialdehyde (Chemical), superoxide (Chemical), glutathione (Chemical), respiratory dysfunction (Disease), ADP (Chemical), isoproterenol (Chemical), salvianolic acid A (Chemical), isoproterenol (Chemical), cardiac dysfunction (Disease), myocardial injury (Disease), salvianolic acid A (Chemical), isoproterenol (Chemical), myocardial damage (Disease), salvianolic acid A (Chemical), isoproterenol (Chemical), myocardial infarction (Disease)


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Input: Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats. The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.

Output: Chemical/Disease Entities: N-(2-propylpentanoyl)urea (Chemical), amino acid (Chemical), pilocarpine (Chemical), seizure (Disease), amino acid (Chemical), glutamate (Chemical), aspartate (Chemical), glycine (Chemical), GABA (Chemical), N-(2-propylpentanoyl)urea (Chemical), VPU (Chemical), valproic acid (Chemical), VPA (Chemical), VPU (Chemical), VPA (Chemical), pilocarpine (Chemical), seizure (Disease), VPA (Chemical), pilocarpine (Chemical), glutamate (Chemical), aspartate (Chemical), glycine (Chemical), GABA (Chemical), VPU (Chemical), VPA (Chemical), pilocarpine (Chemical), glutamate (Chemical), aspartate (Chemical), GABA (Chemical), glycine (Chemical), glutamate (Chemical), aspartate (Chemical), VPU (Chemical), VPA (Chemical), pilocarpine (Chemical), seizure (Disease), amino acid (Chemical), glutamate (Chemical), aspartate (Chemical), VPA (Chemical), VPU (Chemical), pilocarpine (Chemical), glutamate (Chemical), aspartate (Chemical), pilocarpine (Chemical), seizure (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Acute hepatitis attack after exposure to telithromycin. INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of "acute hepatitis of unknown origin," that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.

Output: Chemical/Disease Entities: hepatitis (Disease), telithromycin (Chemical), hepatotoxicity (Disease), hepatic injury (Disease), adverse drug reactions (Disease), jaundice (Disease), nausea (Disease), vomiting (Disease), telithromycin (Chemical), upper respiratory tract infection (Disease), alanine (Chemical), aspartate (Chemical), bilirubin (Chemical), bilirubin (Chemical), alcohol (Chemical), hepatitis (Disease), telithromycin (Chemical), Telithromycin (Chemical), hepatic dysfunction (Disease), adverse drug reaction (Disease), telithromycin (Chemical), hepatitis (Disease), toxic hepatitis (Disease), hepatitis (Disease), telithromycin (Chemical), hepatitis (Disease), telithromycin (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure. BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.

Output: Chemical/Disease Entities: Spironolactone (Chemical), renal insufficiency (Disease), hyperkalemia (Disease), heart failure (Disease), spironolactone (Chemical), heart failure (Disease), hyperkalemia (Disease), renal insufficiency (Disease), heart failure (Disease), spironolactone (Chemical), hyperkalemia (Disease), renal insufficiency (Disease), heart failure (Disease), spironolactone (Chemical), heart failure (Disease), spironolactone (Chemical), hyperkalemia (Disease), K (Chemical), renal insufficiency (Disease), Cr (Chemical), spironolactone (Chemical), hyperkalemia (Disease), renal failure (Disease), hyperkalemia (Disease), diabetes (Disease), potassium (Chemical), potassium (Chemical), renal insufficiency (Disease), creatinine (Chemical), thiazide (Chemical), Spironolactone (Chemical), hyperkalemia (Disease), renal insufficiency (Disease)


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Input: End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.

Output: Chemical/Disease Entities: End-stage renal disease (Disease), ESRD (Disease), cyclosporine (Chemical), tacrolimus (Chemical), nephrotoxic (Disease), end-stage renal disease (Disease), ESRD (Disease), ESRD (Disease), chronic renal failure (Disease), CRF (Disease), CRF (Disease), ESRD (Disease), CRF (Disease), creatinine (Chemical), ESRD (Disease), ESRD (Disease), ESRD (Disease), renal dysfunction (Disease), CRF (Disease), ESRD (Disease), CRF (Disease), ESRD (Disease), creatinine (Chemical), hepatorenal syndrome (Disease), creatinine (Chemical), creatinine (Chemical), CRF (Disease), ESRD (Disease), ESRD (Disease), ESRD (Disease), ESRD (Disease), ESRD (Disease), CRF (Disease), ESRD (Disease), ESRD (Disease), ESRD (Disease), creatinine (Chemical), hepatorenal syndrome (Disease), creatinine (Chemical), CRF (Disease), ESRD (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.

Output: Chemical/Disease Entities: nimodipine (Chemical), acute stroke (Disease), Nimodipine (Chemical), Stroke (Disease), nimodipine (Chemical), reduction in blood pressure (Disease), acute stroke (Disease), BP reduction (Disease), ischemic stroke (Disease), nimodipine (Chemical), nimodipine (Chemical), Nimodipine (Chemical), reduction in systolic BP (Disease), DBP reduction (Disease), DBP reduction (Disease), death (Disease), death (Disease), nimodipine (Chemical), acute stroke (Disease), nimodipine (Chemical), nimodipine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine. BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.

Output: Chemical/Disease Entities: Transient neurologic symptoms (Disease), prilocaine (Chemical), bupivacaine (Chemical), lidocaine (Chemical), transient neurologic symptoms (Disease), TNSs (Disease), lidocaine (Chemical), bupivacaine (Chemical), lidocaine (Chemical), Prilocaine (Chemical), lidocaine (Chemical), prilocaine (Chemical), lidocaine (Chemical), bupivacaine (Chemical), TNSs (Disease), lidocaine (Chemical), glucose (Chemical), prilocaine (Chemical), glucose (Chemical), bupivacaine (Chemical), glucose (Chemical), TNSs (Disease), lidocaine (Chemical), TNSs (Disease), prilocaine (Chemical), bupivacaine (Chemical), TNSs (Disease), lidocaine (Chemical), prilocaine (Chemical), bupivacaine (Chemical), Prilocaine (Chemical), lidocaine (Chemical), TNSs (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: The role of nicotine in smoking-related cardiovascular disease. Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures.

Output: Chemical/Disease Entities: nicotine (Chemical), cardiovascular disease (Disease), Nicotine (Chemical), cardiovascular disease (Disease), nicotine (Chemical), atherosclerosis (Disease), nicotine (Chemical), nicotine (Chemical), carbon monoxide (Chemical), Nicotine (Chemical), thrombosis (Disease), nicotine (Chemical), nicotine (Chemical), nicotine (Chemical), nicotine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Seizure resulting from a venlafaxine overdose. OBJECTIVE: To report a case of venlafaxine overdose. CASE SUMMARY: A 40-year-old woman with major depression took an overdose of venlafaxine in an apparent suicide attempt. After the ingestion of 26 venlafaxine 50-mg tablets, the patient experienced a witnessed generalized seizure. She was admitted to the medical intensive care unit, venlafaxine was discontinued, and no further sequelae were seen. DISCUSSION: To our knowledge, this is the first reported case of venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of available interventions, no emergent therapy was instituted. CONCLUSIONS: The venlafaxine overdose in our patient resulted in a single episode of generalized seizure but elicited no further sequelae.

Output: Chemical/Disease Entities: Seizure (Disease), venlafaxine (Chemical), overdose (Disease), venlafaxine (Chemical), overdose (Disease), major depression (Disease), overdose (Disease), venlafaxine (Chemical), venlafaxine (Chemical), seizure (Disease), venlafaxine (Chemical), venlafaxine (Chemical), overdose (Disease), seizure (Disease), venlafaxine (Chemical), venlafaxine (Chemical), overdose (Disease), seizure (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Effect of nifedipine on renal function in liver transplant recipients receiving tacrolimus. The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.

Output: Chemical/Disease Entities: nifedipine (Chemical), tacrolimus (Chemical), nifedipine (Chemical), tacrolimus (Chemical), tacrolimus (Chemical), hypertensive (Disease), nifedipine (Chemical), nifedipine (Chemical), Nifedipine (Chemical), creatinine (Chemical), nifedipine (Chemical), nephrotoxicity (Disease), tacrolimus (Chemical), hypertension (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Sinus arrest associated with continuous-infusion cimetidine. The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.

Output: Chemical/Disease Entities: Sinus arrest (Disease), cimetidine (Chemical), cimetidine (Chemical), bradyarrhythmias (Disease), leukemia (Disease), cardiac disease (Disease), sinus arrest (Disease), cimetidine (Chemical), arrhythmias (Disease), cimetidine (Chemical), ranitidine (Chemical), sinus arrest (Disease), cimetidine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid. Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.

Output: Chemical/Disease Entities: gall bladder stones (Disease), octreotide (Chemical), ursodeoxycholic acid (Chemical), Octreotide (Chemical), acromegaly (Disease), gall bladder stones (Disease), octreotide (Chemical), acromegalic (Disease), gall stones (Disease), gall stones (Disease), cholesterol (Chemical), cholesterol (Chemical), cholesterol (Chemical), cholesterol (Chemical), cholesterol (Chemical), ursodeoxycholic acid (Chemical), UDCA (Chemical), UDCA (Chemical), gall stone (Disease), cholesterol (Chemical), gall stone (Disease), octreotide (Chemical), gall stones (Disease), cholesterol (Chemical), gall stone disease (Disease), gall stones (Disease), calcium (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Cardiovascular complications associated with terbutaline treatment for preterm labor. Severe cardiovascular complications occurred in eight of 160 patients treated with terbutaline for preterm labor. Associated corticosteroid therapy and twin gestations appear to be predisposing factors. Potential mechanisms of the pathophysiology are briefly discussed.

Output: Chemical/Disease Entities: Cardiovascular complications (Disease), terbutaline (Chemical), preterm labor (Disease), cardiovascular complications (Disease), terbutaline (Chemical), preterm labor (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Neurologic effects of subarachnoid administration of 2-chloroprocaine-CE, bupivacaine, and low pH normal saline in dogs. The purpose of this study was to evaluate the neurologic consequences of deliberate subarachnoid injection of large volumes of 2-chloroprocaine-CE in experimental animals. The possible role of low pH as well as total volume as potential factors in causing neurotoxicity was evaluated. The 65 dogs in the study received injections in the subarachnoid space as follows: 6 to 8 ml of bupivacaine (N = 15), 2-chloroprocaine-CE (N = 20), low pH normal saline (pH 3.0) (N = 20), or normal saline (N = 10). Of the 20 animals that received subarachnoid injection of 2-chloroprocaine-CE seven (35%) developed hind-limb paralysis. None of the animals that received bupivacaine, normal saline, or normal saline titrated to a pH 3.0 developed hind-limb paralysis. Of the 15 spinal cords of the animals that received 2-chloroprocaine-CE, 13 showed subpial necrosis; the nerve roots and subarachnoid vessels were normal. The spinal cords of the animals that received bupivacaine, low pH normal saline (pH 3.0), or normal saline did not show abnormal findings.

Output: Chemical/Disease Entities: 2-chloroprocaine-CE (Chemical), bupivacaine (Chemical), 2-chloroprocaine-CE (Chemical), neurotoxicity (Disease), bupivacaine (Chemical), 2-chloroprocaine-CE (Chemical), 2-chloroprocaine-CE (Chemical), paralysis (Disease), bupivacaine (Chemical), paralysis (Disease), 2-chloroprocaine-CE (Chemical), subpial necrosis (Disease), bupivacaine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Early adjuvant adriamycin in superficial bladder carcinoma. A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.

Output: Chemical/Disease Entities: adriamycin (Chemical), Adriamycin (Chemical), bladder tumors (Disease), cystitis (Disease), tumors (Disease), tumor (Disease), Adriamycin (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Hyperkalemia associated with sulindac therapy. Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.

Output: Chemical/Disease Entities: Hyperkalemia (Disease), sulindac (Chemical), Hyperkalemia (Disease), indomethacin (Chemical), sulindac (Chemical), prostacyclin (Chemical), hyperkalemia (Disease), sulindac (Chemical), potassium (Chemical), sulindac (Chemical), potassium (Chemical), sulindac (Chemical), hyperkalemia (Disease), sulindac (Chemical)


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Input: Ventricular tachyarrhythmias during cesarean section after ritodrine therapy: interaction with anesthetics. This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.

Output: Chemical/Disease Entities: Ventricular tachyarrhythmias (Disease), ritodrine (Chemical), ritodrine (Chemical), preterm labor (Disease), ritodrine (Chemical), cardiovascular complications (Disease), ritodrine (Chemical), potassium (Chemical), ephedrine (Chemical), phenylephrine (Chemical), hypotensive (Disease), tachycardia (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Immunohistochemical, electron microscopic and morphometric studies of estrogen-induced rat prolactinomas after bromocriptine treatment. To clarify the effects of bromocriptine on prolactinoma cells in vivo, immunohistochemical, ultrastructural and morphometrical analyses were applied to estrogen-induced rat prolactinoma cells 1 h and 6 h after injection of bromocriptine (3 mg/kg of body weight). One h after treatment, serum prolactin levels decreased markedly. Electron microscopy disclosed many secretory granules, slightly distorted rough endoplasmic reticulum, and partially dilated Golgi cisternae in the prolactinoma cells. Morphometric analysis revealed that the volume density of secretory granules increased, while the volume density of cytoplasmic microtubules decreased. These findings suggest that lowered serum prolactin levels in the early phase of bromocriptine treatment may result from an impaired secretion of prolactin due to decreasing numbers of cytoplasmic microtubules. At 6 h after injection, serum prolactin levels were still considerably lower than in controls. The prolactinoma cells at this time were well granulated, with vesiculated rough endoplasmic reticulum and markedly dilated Golgi cisternae. Electron microscopical immunohistochemistry revealed positive reaction products noted on the secretory granules, Golgi cisternae, and endoplasmic reticulum of the untreated rat prolactinoma cells. However, only secretory granules showed the positive reaction products for prolactin 6 h after bromocriptine treatment of the adenoma cells. An increase in the volume density of secretory granules and a decrease in the volume densities of rough endoplasmic reticulum and microtubules was determined by morphometric analysis, suggesting that bromocriptine inhibits protein synthesis as well as bringing about a disturbance of the prolactin secretion.

Output: Chemical/Disease Entities: estrogen (Chemical), prolactinomas (Disease), bromocriptine (Chemical), bromocriptine (Chemical), prolactinoma (Disease), estrogen (Chemical), prolactinoma (Disease), bromocriptine (Chemical), prolactinoma (Disease), bromocriptine (Chemical), prolactinoma (Disease), prolactinoma (Disease), bromocriptine (Chemical), adenoma (Disease), bromocriptine (Chemical)


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Input: On two paradoxical side-effects of prednisolone in rats, ribosomal RNA biosyntheses, and a mechanism of action. Liver enlargement and muscle wastage occurred in Wistar rats following the subcutaneous administration of prednisolone. In the liver both the content of RNA and the biosynthesis of ribosomal RNA increased while both the RNA content and ribosomal RNA biosynthesis were reduced in the gastrocnemius muscle. It is suggested that the drug acted in a selective and tissue-specific manner to enhance ribosomal RNA synthesis in the liver and depress such synthesis in the muscle. This view supports the contention that the liver and muscle are independent sites of prednisolone action.

Output: Chemical/Disease Entities: prednisolone (Chemical), Liver enlargement (Disease), muscle wastage (Disease), prednisolone (Chemical), prednisolone (Chemical)


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Input: Possible intramuscular midazolam-associated cardiorespiratory arrest and death. Midazolam hydrochloride is commonly used for dental or endoscopic procedures. Although generally consisted safe when given intramuscularly, intravenous administration is known to cause respiratory and cardiovascular depression. This report describes the first published case of cardiorespiratory arrest and death associated with intramuscular administration of midazolam. Information regarding midazolam use is reviewed to provide recommendation for safe administration.

Output: Chemical/Disease Entities: midazolam (Chemical), cardiorespiratory arrest (Disease), death (Disease), Midazolam hydrochloride (Chemical), cardiorespiratory arrest (Disease), death (Disease), midazolam (Chemical), midazolam (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Serial epilepsy caused by levodopa/carbidopa administration in two patients on hemodialysis. Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high-flux dialyzer; both had been receiving a carbidopa/levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation.

Output: Chemical/Disease Entities: epilepsy (Disease), levodopa/carbidopa (Chemical), chronic renal failure (Disease), carbidopa/levodopa (Chemical), hallucinosis (Disease), seizures (Disease), vitamin B6 (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine. The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.

Output: Chemical/Disease Entities: L-alpha-glyceryl-phosphorylcholine (Chemical), amnesia (Disease), scopolamine (Chemical), L-alpha-glycerylphosphorylcholine (Chemical), L-alpha-GFC (Chemical), memory impairment (Disease), scopolamine (Chemical), L-alpha-GFC (Chemical), scopolamine (Chemical), impairment of attention and memory (Disease), scopolamine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Seizures induced by the cocaine metabolite benzoylecgonine in rats. The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.

Output: Chemical/Disease Entities: Seizures (Disease), cocaine (Chemical), benzoylecgonine (Chemical), cocaine (Chemical), seizures (Disease), strokes (Disease), cocaine (Chemical), cocaine (Chemical), benzoylecgonine (Chemical), BE (Chemical), seizures (Disease), cocaine (Chemical), BE (Chemical), seizure (Disease), seizures (Disease), BE (Chemical), seizures (Disease), cocaine (Chemical), cocaine (Chemical), seizures (Disease), death (Disease), BE (Chemical), death (Disease), seizure (Disease), BE (Chemical), seizures (Disease), cocaine (Chemical), seizures (Disease), cocaine (Chemical), BE (Chemical), seizures (Disease), cocaine (Chemical), seizures (Disease), cocaine (Chemical), BE (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist. LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.

Output: Chemical/Disease Entities: amphetamine (Chemical), neurotoxicity (Disease), dopamine (Chemical), LY274614 (Chemical), amino acid (Chemical), LY274614 (Chemical), 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid (Chemical), N-methyl-D-aspartate (Chemical), NMDA (Chemical), glutamate (Chemical), dopamine (Chemical), amphetamine (Chemical), iprindole (Chemical), amphetamine (Chemical), iprindole (Chemical), dopamine (Chemical), dopamine (Chemical), dizocilpine (Chemical), MK-801 (Chemical), NMDA (Chemical), LY274614 (Chemical), NMDA (Chemical), LY274614 (Chemical), LY274614 (Chemical), dopamine (Chemical), amphetamine (Chemical), amphetamine (Chemical), dopamine (Chemical), LY274614 (Chemical), amphetamine (Chemical), LY274614 (Chemical), amphetamine (Chemical), dopamine (Chemical), methamphetamine (Chemical), LY274614 (Chemical), neurotoxic (Disease), amphetamine (Chemical), dopamine (Chemical), NMDA (Chemical), LY274614 (Chemical), NMDA (Chemical)


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Input: Neonatal pyridoxine responsive convulsions due to isoniazid therapy. A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.

Output: Chemical/Disease Entities: pyridoxine (Chemical), convulsions (Disease), isoniazid (Chemical), isoniazid (Chemical), tuberculosis (Disease), clonic fits (Disease), fits (Disease), pyridoxine (Chemical), pyridoxine (Chemical), isoniazid (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Reversal by phenylephrine of the beneficial effects of intravenous nitroglycerin in patients with acute myocardial infarction. Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.

Output: Chemical/Disease Entities: phenylephrine (Chemical), nitroglycerin (Chemical), acute myocardial infarction (Disease), Nitroglycerin (Chemical), acute myocardial infarction (Disease), nitroglycerin (Chemical), hypotension (Disease), nitroglycerin (Chemical), phenylephrine (Chemical), myocardial infarctions (Disease), nitroglycerin (Chemical), nitroglycerin (Chemical), phenylephrine (Chemical), phenylephrine (Chemical), nitroglycerin (Chemical), acute myocardial infarction (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model. PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.

Output: Chemical/Disease Entities: CaCl2 (Chemical), thoracic aortic aneurysm (Disease), thoracic aortic aneurysm (Disease), TAA (Disease), calcium chloride (Chemical), CaCl(2) (Chemical), arterial injury (Disease), TAA (Disease), CaCl(2) (Chemical), NaCl (Chemical), CaCl(2) (Chemical), CaCl(2) (Chemical), NaCl (Chemical), CaCl(2) (Chemical), CaCl(2) (Chemical), NaCl (Chemical), CaCl(2) (Chemical), CaCl(2) (Chemical), CaCl(2) (Chemical), NaCl (Chemical), CaCl(2) (Chemical), TAA (Disease), CaCl(2) (Chemical)


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Input: When drugs disappear from the patient: elimination of intravenous medication by hemodiafiltration. Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.

Output: Chemical/Disease Entities: right heart failure (Disease), catecholamines (Chemical), epinephrine (Chemical), hypertensive (Disease), catecholamine (Chemical)


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Input: Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel. Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.

Output: Chemical/Disease Entities: glutamate (Chemical), peripheral neurotoxicity (Disease), paclitaxel (Chemical), peripheral neuropathy (Disease), paclitaxel (Chemical), PAC (Chemical), glutamate (Chemical), amino acid (Chemical), glutamine (Chemical), PAC (Chemical), neurotoxicity (Disease), glutamate (Chemical), PAC (Chemical), peripheral neuropathy (Disease), ovarian cancer (Disease), PAC (Chemical), glutamate (Chemical), neurotoxicity (Disease), pain (Disease), glutamate (Chemical), peripheral neurotoxicity (Disease), PAC (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Attentional modulation of perceived pain intensity in capsaicin-induced secondary hyperalgesia. Perceived pain intensity is modulated by attention. However, it is not known that how pain intensity ratings are affected by attention in capsaicin-induced secondary hyperalgesia. Here we show that perceived pain intensity in secondary hyperalgesia is decreased when attention is distracted away from the painful pinprick stimulus with a visual task. Furthermore, it was found that the magnitude of attentional modulation in secondary hyperalgesia is very similar to that of capsaicin-untreated, control condition. Our findings, showing no interaction between capsaicin treatment and attentional modulation suggest that capsaicin-induced secondary hyperalgesia and attention might affect mechanical pain through independent mechanisms.

Output: Chemical/Disease Entities: pain (Disease), capsaicin (Chemical), hyperalgesia (Disease), pain (Disease), pain (Disease), capsaicin (Chemical), hyperalgesia (Disease), pain (Disease), hyperalgesia (Disease), hyperalgesia (Disease), capsaicin (Chemical), capsaicin (Chemical), capsaicin (Chemical), hyperalgesia (Disease), pain (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats. Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.

Output: Chemical/Disease Entities: Testosterone (Chemical), hypertension (Disease), salt (Chemical), salt (Chemical), salt (Chemical), salt (Chemical), angiotensin (Chemical), testosterone (Chemical), renal injury (Disease), salt (Chemical), glomerular sclerosis (Disease), Testosterone (Chemical), renal injury (Disease), Testosterone (Chemical), hypertension (Disease), renal injury (Disease), angiotensin (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Prenatal protein deprivation alters dopamine-mediated behaviors and dopaminergic and glutamatergic receptor binding. Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.

Output: Chemical/Disease Entities: dopamine (Chemical), schizophrenia (Disease), schizophrenia (Disease), apomorphine (Chemical), amphetamine (Chemical), haloperidol (Chemical), catalepsy (Disease), MK-801 (Chemical), H (Chemical), MK-801 (Chemical), H (Chemical), haloperidol (Chemical), dopamine (Chemical), H (Chemical), MK-801 (Chemical), nutritional deficiency (Disease), schizophrenia (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: mToR inhibitors-induced proteinuria: mechanisms, significance, and management. Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria.

Output: Chemical/Disease Entities: proteinuria (Disease), rapamycin (Chemical), sirolimus (Chemical), chronic allograft nephropathy (Disease), proteinuria (Disease), proteinuria (Disease), sirolimus (Chemical), proteinuria (Disease), sirolimus (Chemical), sirolimus (Chemical), glomerulosclerosis (Disease), proteinuria (Disease)