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

Input: Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety. BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.

Output: Chemical/Disease Entities: Norepinephrine (Chemical), cocaine (Chemical), anxiety (Disease), Cocaine (Chemical), cocaine (Chemical), cocaine (Chemical), anxiety (Disease), dopamine (Chemical), norepinephrine (Chemical), NE (Chemical), cocaine (Chemical), anxiety (Disease), cocaine (Chemical), anxiety (Disease), cocaine (Chemical), Cocaine (Chemical), anxiety (Disease), disulfiram (Chemical), dopamine (Chemical), propranolol (Chemical), cocaine (Chemical), anxiety (Disease), prazosin (Chemical), yohimbine (Chemical), cocaine (Chemical), anxiety (Disease)


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

Input: Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis. OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.

Output: Chemical/Disease Entities: Clonidine (Chemical), attention-deficit/hyperactivity disorder (Disease), clonidine (Chemical), methylphenidate (Chemical), attention-deficit/hyperactivity disorder (Disease), ADHD (Disease), ADHD (Disease), clonidine (Chemical), methylphenidate (Chemical), clonidine (Chemical), methylphenidate (Chemical), clonidine (Chemical), methylphenidate (Chemical), bradycardia (Disease), clonidine (Chemical), clonidine (Chemical), clonidine (Chemical), methylphenidate (Chemical), clonidine (Chemical), Drowsiness (Disease), clonidine (Chemical), Clonidine (Chemical), methylphenidate (Chemical), ADHD (Disease), clonidine (Chemical), bradycardia (Disease), drowsiness (Disease)


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Input: Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B. Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.

Output: Chemical/Disease Entities: Thalidomide (Chemical), non-Hodgkin lymphomas (Disease), Cancer (Disease), Leukemia (Disease), Thalidomide (Chemical), multiple myeloma (Disease), mantle cell lymphoma (Disease), lymphoplasmacytic lymphoma (Disease), tumour (Disease), lymphomas (Disease), thalidomide (Chemical), myelosuppression (Disease), fatigue (Disease), somnolence (Disease), depressed mood (Disease), neuropathy (Disease), dyspnea (Disease), thromboembolic (Disease), thalidomide (Chemical), lymphomas (Disease), lenalidomide (Chemical)


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Input: Intracavernous epinephrine: a minimally invasive treatment for priapism in the emergency department. Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45-year-old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed.

Output: Chemical/Disease Entities: epinephrine (Chemical), priapism (Disease), Priapism (Disease), cocaine (Chemical), priapism (Disease), cocaine (Chemical), epinephrine (Chemical)


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

Input: Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats. The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.

Output: Chemical/Disease Entities: green tea (Chemical), vitamin E (Chemical), isoproterenol (Chemical), myocardial infarction (Disease), green tea (Chemical), vitamin E (Chemical), isoproterenol (Chemical), ISO (Chemical), myocardial infarction (Disease), ISO (Chemical), Ca (Chemical), Na (Chemical), K (Chemical), Mg (Chemical), green tea (Chemical), vitamin E (Chemical), ISO (Chemical), Ca (Chemical), Na (Chemical), K (Chemical), Mg (Chemical), ISO (Chemical), green tea (Chemical), vitamin E (Chemical), green tea (Chemical), vitamin E (Chemical), ISO (Chemical), myocardial infarction (Disease)


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Input: Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C. A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.

Output: Chemical/Disease Entities: ocular myasthenia (Disease), pegylated interferon (Chemical), ribavirin (Chemical), chronic hepatitis C (Disease), diplopia (Disease), pegylated interferon (IFN) alpha-2b (Chemical), ribavirin (Chemical), chronic hepatitis C (Disease), CHC (Disease), ptosis on the right upper lid (Disease), restricted right eye movement (Disease), acetylcholine (Chemical), pegylated IFN alpha-2b (Chemical), ribavirin (Chemical), ocular myasthenia (Disease), pegylated IFN alpha-2b (Chemical), ribavirin (Chemical), CHC (Disease), IFN (Chemical)


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

Input: The glycine transporter-1 inhibitor SSR103800 displays a selective and specific antipsychotic-like profile in normal and transgenic mice. Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.

Output: Chemical/Disease Entities: glycine (Chemical), SSR103800 (Chemical), Schizophrenia (Disease), dopamine (Chemical), glutamate (Chemical), N-methyl-D-aspartate (Chemical), NMDA (Chemical), schizophrenic (Disease), NMDA (Chemical), NMDA (Chemical), glycine (Chemical), SSR103800 (Chemical), NMDA (Chemical), glycine (Chemical), NMDA (Chemical), SSR103800 (Chemical), hyperactivity (Disease), amphetamine (Chemical), MK-801 (Chemical), NMDA (Chemical), SSR103800 (Chemical), hyperactivity (Disease), NMDA (Chemical), MK-801 (Chemical), hyperactivity (Disease), NMDA (Chemical), SSR103800 (Chemical), hyperactivity (Disease), amphetamine (Chemical), dopamine (Chemical), haloperidol (Chemical), olanzapine (Chemical), clozapine (Chemical), aripiprazole (Chemical), hyperactivity (Disease), SSR103800 (Chemical), catalepsy (Disease), SSR103800 (Chemical)


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

Input: Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension. BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.

Output: Chemical/Disease Entities: Phenylephrine (Chemical), ephedrine (Chemical), reduces frontal lobe oxygenation (Disease), hypotension (Disease), hypotension (Disease), phenylephrine (Chemical), ephedrine (Chemical), hypotension (Disease), fentanyl (Chemical), propofol (Chemical), phenylephrine (Chemical), ephedrine (Chemical), stroke (Disease), phenylephrine (Chemical), ephedrine (Chemical), phenylephrine (Chemical), hypotension (Disease), ephedrine (Chemical)


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Input: A novel, multiple symptom model of obsessive-compulsive-like behaviors in animals. BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.

Output: Chemical/Disease Entities: obsessive-compulsive-like behaviors (Disease), obsessive-compulsive disorder (Disease), OCD (Disease), anxiety (Disease), OCD (Disease), antidepressant (Chemical), clomipramine (Chemical), Clomipramine (Chemical), anxiety (Disease), behavioral inflexibility (Disease), memory impairment (Disease), hoarding (Disease), corticostriatal dysfunction (Disease), Dopamine (Chemical), serotonin (Chemical), serotonin (Chemical), OCD (Disease), OCD (Disease), OCD (Disease), psychiatric disorders (Disease)


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Input: Late recovery of renal function in a woman with the hemolytic uremic syndrome. A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.

Output: Chemical/Disease Entities: hemolytic uremic syndrome (Disease), hemolytic uremic syndrome (Disease), HUS (Disease), oral contraceptives (Chemical), heparin (Chemical), dipyridamole (Chemical), anuria (Disease), HUS (Disease), oliguria (Disease), HUS (Disease), hypertension (Disease), microangiopathic hemolytic anemia (Disease)


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

Input: Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs. A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.

Output: Chemical/Disease Entities: acetylsalicylic acid (Chemical), dipyridamole (Chemical), hydrocortisone (Chemical), epinephrine (Chemical), myocardial injury (Disease), myocardial injury (Disease), epinephrine (Chemical), myocardial infarction (Disease), epinephrine (Chemical), radiocalcium (Chemical), calcium (Chemical), calcium chloride (Chemical), calcium (Chemical), calcium (Chemical), radiocalcium (Chemical), acetylsalicylic acid (Chemical), dipyridamole (Chemical), hydrocortisone (Chemical), epinephrine (Chemical), calcium (Chemical), Acetylsalicylic acid (Chemical), dipyridamole (Chemical), hydrocortisone (Chemical)


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Input: Changes in depressive status associated with topical beta-blockers. Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.

Output: Chemical/Disease Entities: depressive (Disease), Depression (Disease), sexual dysfunction (Disease), timolol (Chemical), betaxolol (Chemical), glaucomatous (Disease), timolol (Chemical), depression (Disease), depression (Disease), timolol (Chemical), depression (Disease), betaxolol (Chemical), depression (Disease), timolol (Chemical)


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Input: Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report. The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.

Output: Chemical/Disease Entities: ifosfamide (Chemical), renal toxicity (Disease), malignant mesenchymal tumors (Disease), malignant mesenchymal tumors (Disease), ifosfamide (Chemical), Malignant Mesenchymal Tumor (Disease), ifosfamide (Chemical), ifosfamide, vincristine, and dactinomycin (Chemical), IVA (Chemical), cisplatin (Chemical), tumor (Disease), glucosuria (Disease), proteinuria (Disease), aminoaciduria (Disease), creatinine (Chemical), phosphate (Chemical), renal abnormalities (Disease), toxicity (Disease), Fanconi's syndrome (Disease), TDFS (Disease), phosphate (Chemical), toxicity (Disease), ifosfamide (Chemical), tumor (Disease), ifosfamide (Chemical), mesenchymal tumors (Disease)


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Input: Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats. Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.

Output: Chemical/Disease Entities: dopamine (Chemical), nicotine (Chemical), hyperactivity (Disease), nicotine (Chemical), nicotine (Chemical), dopamine (Chemical), nicotine (Chemical), dopamine (Chemical), nicotine (Chemical), Nicotine (Chemical), increase in locomotor activity (Disease), nicotine (Chemical), mecamylamine (Chemical), hexamethonium (Chemical), Nicotine (Chemical), hyperactivity (Disease), SCH 23390 (Chemical), raclopride (Chemical), fluphenazine (Chemical), PHNO (Chemical), nicotine (Chemical), hyperactivity (Disease), SKF 38393 (Chemical), nicotine (Chemical), hyperactivity (Disease), nicotine (Chemical), dopamine (Chemical)


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

Input: Neuropsychiatric side effects after the use of mefloquine. This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.

Output: Chemical/Disease Entities: mefloquine (Chemical), mefloquine (Chemical), seizures (Disease), psychoses (Disease), anxiety neurosis (Disease), disturbances of sleep-wake rhythm (Disease), mefloquine (Chemical), mefloquine (Chemical), malaria (Disease), mefloquine (Chemical)


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Input: Reduction in injection pain using buffered lidocaine as a local anesthetic before cardiac catheterization. Previous reports have suggested that pain associated with the injection of lidocaine is related to the acidic pH of the solution. To determine if the addition of a buffering solution to adjust the pH of lidocaine into the physiologic range would reduce pain during injection, we performed a blinded randomized study in patients undergoing cardiac catheterization. Twenty patients were asked to quantify the severity of pain after receiving standard lidocaine in one femoral area and buffered lidocaine in the opposite femoral area. The mean pain score for buffered lidocaine was significantly lower than the mean score for standard lidocaine (2.7 +/- 1.9 vs. 3.8 +/- 2.2, P = 0.03). The pH adjustment of standard lidocaine can be accomplished easily in the catheterization laboratory before injection and results in a reduction of the pain occurring during the infiltration of tissues.

Output: Chemical/Disease Entities: pain (Disease), lidocaine (Chemical), pain (Disease), lidocaine (Chemical), lidocaine (Chemical), pain (Disease), pain (Disease), lidocaine (Chemical), lidocaine (Chemical), pain (Disease), lidocaine (Chemical), lidocaine (Chemical), lidocaine (Chemical), pain (Disease)


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

Input: Randomized, double-blind trial of mazindol in Duchenne dystrophy. There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.

Output: Chemical/Disease Entities: mazindol (Chemical), Duchenne dystrophy (Disease), weakness (Disease), Duchenne dystrophy (Disease), mazindol (Chemical), Duchenne dystrophy (Disease), mazindol (Chemical), weakness (Disease), Mazindol (Chemical), mazindol (Chemical), decreased appetite (Disease), dry mouth (Disease), gastrointestinal symptoms (Disease), mazindol (Chemical), mazindol (Chemical), mazindol (Chemical), mazindol (Chemical), Mazindol (Chemical), weakness (Disease), Duchenne dystrophy (Disease)


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

Input: Pentoxifylline (Trental) does not inhibit dipyridamole-induced coronary hyperemia: implications for dipyridamole-thallium-201 myocardial imaging. Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.

Output: Chemical/Disease Entities: Pentoxifylline (Chemical), Trental (Chemical), dipyridamole (Chemical), hyperemia (Disease), dipyridamole (Chemical), thallium (Chemical), Dipyridamole (Chemical), thallium (Chemical), peripheral vascular disease (Disease), pentoxifylline (Chemical), Trental (Chemical), methylxanthine (Chemical), intermittent claudication (Disease), pentoxifylline (Chemical), dipyridamole (Chemical), hyperemia (Disease), methylxanthines (Chemical), theophylline (Chemical), dipyridamole (Chemical), thallium (Chemical), dipyridamole (Chemical), pentoxifylline (Chemical), theophylline (Chemical), Dipyridamole (Chemical), pentoxifylline (Chemical), pentoxifylline (Chemical), dipyridamole (Chemical), hyperemia (Disease), theophylline (Chemical), pentoxyifylline (Chemical), dipyridamole (Chemical), hyperemia (Disease)


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

Input: Cause of death among patients with Parkinson's disease: a rare mortality due to cerebral haemorrhage. Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.

Output: Chemical/Disease Entities: death (Disease), Parkinson's disease (Disease), cerebral haemorrhage (Disease), death (Disease), cerebral haemorrhage (Disease), Parkinson's disease (Disease), death (Disease), pneumonia (Disease), bronchitis (Disease), neoplasms (Disease), heart diseases (Disease), cerebral infarction (Disease), septicaemia (Disease), Cerebral haemorrhage (Disease), death (Disease), deaths (Disease), death (Disease), cerebral haemorrhage (Disease), death (Disease), Parkinson's disease (Disease), hypotensive (Disease), levodopa (Chemical), hypotensive (Disease), noradrenaline (Chemical), parkinsonian (Disease)


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

Input: Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever. Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.

Output: Chemical/Disease Entities: ribavirin (Chemical), Argentine hemorrhagic fever (Disease), ribavirin (Chemical), Argentine hemorrhagic fever (Disease), AHF (Disease), ribavirin (Chemical), viremia (Disease), death (Disease), anemia (Disease), ribavirin (Chemical), AHF (Disease), anemia (Disease), ribavirin (Chemical), AHF (Disease)


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

Input: Dipyridamole-induced myocardial ischemia. Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary "steal" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.

Output: Chemical/Disease Entities: Dipyridamole (Chemical), myocardial ischemia (Disease), Angina (Disease), dipyridamole (Chemical), dipyridamole (Chemical), dipyridamole (Chemical), myocardial ischemia (Disease), coronary artery disease (Disease), dipyridamole (Chemical), ischemia (Disease)


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

Input: Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback. Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.

Output: Chemical/Disease Entities: Nitroprusside (Chemical), hypotension (Disease), arginine vasopressin (Chemical), oxytocin (Chemical), corticosterone (Chemical), urethane (Chemical), arginine vasopressin (Chemical), oxytocin (Chemical), corticosterone (Chemical), corticosterone (Chemical), corticosterone (Chemical), nitroprusside (Chemical), hypotension (Disease), corticosterone (Chemical)


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

Input: Noradrenergic involvement in catalepsy induced by delta 9-tetrahydrocannabinol. In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.

Output: Chemical/Disease Entities: catalepsy (Disease), delta 9-tetrahydrocannabinol (Chemical), delta 9-tetrahydrocannabinol (Chemical), THC (Chemical), 6-hydroxydopamine (Chemical), 6-OHDA (Chemical), desipramine (Chemical), 6-OHDA (Chemical), THC (Chemical), 6-OHDA (Chemical), desipramine (Chemical), 6-OHDA (Chemical), haloperidol (Chemical), desipramine (Chemical), 6-OHDA (Chemical), 6-OHDA (Chemical), catalepsy (Disease), THC (Chemical), catalepsy (Disease), haloperidol (Chemical)


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

Input: Intracranial pressure increases during alfentanil-induced rigidity. Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +/- 1 mmHg, mean +/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +/- 1.0 mmHg, delta CVP 5.9 +/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.

Output: Chemical/Disease Entities: alfentanil (Chemical), rigidity (Disease), alfentanil (Chemical), rigidity (Disease), halothane (Chemical), halothane (Chemical), alfentanil (Chemical), halothane (Chemical), somatic rigidity (Disease), rigidity (Disease), metocurine (Chemical), alfentanil (Chemical), rigidity (Disease), alfentanil (Chemical)


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

Input: Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil. Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.

Output: Chemical/Disease Entities: cis-platin (Chemical), 5-fluorouracil (Chemical), head and neck carcinoma (Disease), esophageal carcinoma (Disease), cis-platin (Chemical), 5-FU (Chemical), cardiovascular disease (Disease), cardiotoxicity (Disease), cardiovascular disease (Disease), cardiotoxicity (Disease), chest pain (Disease), atrial fibrillation (Disease), ventricular fibrillation (Disease), sudden death (Disease), 5-FU (Chemical), chest pain (Disease), tachyarrhythmia (Disease)


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

Input: Verapamil-induced carbamazepine neurotoxicity. A report of two cases. Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half).

Output: Chemical/Disease Entities: Verapamil (Chemical), carbamazepine (Chemical), neurotoxicity (Disease), carbamazepine (Chemical), neurotoxicity (Disease), verapamil (Chemical), calcium (Chemical), verapamil (Chemical), carbamazepine (Chemical), carbamazepine (Chemical), carbamazepine (Chemical)


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

Input: Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy. Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.

Output: Chemical/Disease Entities: auditory neurotoxicity (Disease), deferoxamine (Chemical), anemia (Disease), iron (Chemical), deferoxamine (Chemical), abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz (Disease), deferoxamine (Chemical), permanent disability (Disease), deferoxamine (Chemical), auditory abnormality (Disease), toxicity (Disease), deferoxamine (Chemical), deferoxamine (Chemical), ototoxicity (Disease), deferoxamine (Chemical), toxicity (Disease), deferoxamine (Chemical), hearing loss (Disease), auditory dysfunction (Disease)


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

Input: Flurbiprofen in the treatment of juvenile rheumatoid arthritis. Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.

Output: Chemical/Disease Entities: Flurbiprofen (Chemical), juvenile rheumatoid arthritis (Disease), juvenile rheumatoid arthritis (Disease), flurbiprofen (Chemical), arthritis (Disease), tender joints (Disease), swelling (Disease), tenderness (Disease), morning stiffness (Disease), fecal occult blood (Disease), gastrointestinal (GI) bleeding (Disease), headache (Disease), abdominal pain (Disease)


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

Input: The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats. The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.

Output: Chemical/Disease Entities: neurotoxic (Disease), mipafox (Chemical), neuropathic damage (Disease), neuropathic damage (Disease), neurotoxic (Disease), neuropathy (Disease), Mipafox (Chemical), N, N'-diisopropylphosphorodiamidofluoridate (Chemical), neurotoxic (Disease), organophosphate (Chemical), Mipafox (Chemical), cord damage (Disease), Mipafox (Chemical), cord damage (Disease), Mipafox (Chemical), neuropathic damage (Disease)


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

Input: Cerebral infarction with a single oral dose of phenylpropanolamine. Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.

Output: Chemical/Disease Entities: Cerebral infarction (Disease), phenylpropanolamine (Chemical), Phenylpropanolamine (Chemical), PPA (Chemical), amphetamine (Chemical), seizures (Disease), intracerebral hemorrhage (Disease), neuropsychiatric symptoms (Disease), cerebral infarction (Disease), cerebral infarction (Disease), PPA (Chemical)


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

Input: Treatment of psoriasis with azathioprine. Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.

Output: Chemical/Disease Entities: psoriasis (Disease), azathioprine (Chemical), Azathioprine (Chemical), psoriasis (Disease), cholestasis (Disease), fibrosis (Disease), azathioprine (Chemical), liver damage (Disease)


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

Input: Maternal lithium and neonatal Ebstein's anomaly: evaluation with cross-sectional echocardiography. Cross-sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein's anomaly of the tricuspid valve was identified. In the other infant cross-sectional echocardiography provided reassurance that the infant did not have Ebstein's anomaly. Cross-sectional echocardiographic screening of newborns exposed to lithium during gestation can provide highly accurate, noninvasive assessment of the presence or absence of lithium-induced cardiac malformations.

Output: Chemical/Disease Entities: lithium (Chemical), Ebstein's anomaly (Disease), lithium (Chemical), Ebstein's anomaly (Disease), Ebstein's anomaly (Disease), lithium (Chemical), lithium (Chemical), cardiac malformations (Disease)


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

Input: Effects of training on the extent of experimental myocardial infarction in aging rats. The effects of exercise on the severity of isoproterenol-induced myocardial infarction were studied in female albino rats of 20,40,60 and 80 weeks of age. The rats were trained to swim for a specific duration and for a particular period. The occurrence of infarcts were confirmed by histological methods. Elevations in the serum GOT and GPT were maximum in the sedentary-isoproterenols and minimum in the exercise-controls. These changes in the serum transaminases were associated with corresponding depletions in the cardiac GOT and GPT. However, age was seen to interfere with the responses exhibited by the young and old rats. Studies dealing with myocardial infarction are more informative when dealt with age.

Output: Chemical/Disease Entities: myocardial infarction (Disease), isoproterenol (Chemical), myocardial infarction (Disease), infarcts (Disease), isoproterenols (Chemical), myocardial infarction (Disease)


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

Input: Effect of polyethylene glycol 400 on adriamycin toxicity in mice. The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.

Output: Chemical/Disease Entities: polyethylene glycol 400 (Chemical), adriamycin (Chemical), toxicity (Disease), polyethylene glycol 400 (Chemical), PEG 400 (Chemical), adriamycin (Chemical), ADR (Chemical), PEG 400 (Chemical), ADR (Chemical), ADR (Chemical), cardiac morphological alterations (Disease), ADR (Chemical), L1210 leukemia (Disease), Ehrlich ascites tumor (Disease)


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

Input: Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system. Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.

Output: Chemical/Disease Entities: BCNU (Chemical), malignant gliomas (Disease), BCNU (Chemical), 1,3-bis-(2-chloroethyl)-1-nitrosourea (Chemical), malignant gliomas (Disease), BCNU (Chemical), astrocytomas (Disease), tumor (Disease), tumor (Disease), edema (Disease), astrocytomas (Disease), BCNU (Chemical), BCNU (Chemical), loss of vision (Disease), retinal vasculitis (Disease), visual loss (Disease), ethanol (Chemical)


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

Input: Blood pressure response to chronic low-dose intrarenal noradrenaline infusion in conscious rats. Sodium chloride solution (0.9%) or noradrenaline in doses of 4, 12 and 36 micrograms h-1 kg-1 was infused for five consecutive days, either intrarenally (by a new technique) or intravenously into rats with one kidney removed. Intrarenal infusion of noradrenaline caused hypertension at doses which did not do so when infused intravenously. Intrarenal compared with intravenous infusion of noradrenaline caused higher plasma noradrenaline concentrations and a shift of the plasma noradrenaline concentration-blood pressure effect curve towards lower plasma noradrenaline levels. These results suggest that hypertension after chronic intrarenal noradrenaline infusion is produced by relatively higher levels of circulating noradrenaline and by triggering of an additional intrarenal pressor mechanism.

Output: Chemical/Disease Entities: noradrenaline (Chemical), Sodium chloride (Chemical), noradrenaline (Chemical), noradrenaline (Chemical), hypertension (Disease), noradrenaline (Chemical), noradrenaline (Chemical), noradrenaline (Chemical), noradrenaline (Chemical), hypertension (Disease), noradrenaline (Chemical), noradrenaline (Chemical)


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

Input: Age and renal clearance of cimetidine. In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram/ml. Thus, high cimetidine levels alone do not always induce dementia.

Output: Chemical/Disease Entities: cimetidine (Chemical), cimetidine (Chemical), cimetidine (Chemical), creatinine (Chemical), Cimetidine (Chemical), cimetidine (Chemical), cimetidine (Chemical), cimetidine (Chemical), creatinine (Chemical), cimetidine (Chemical), cimetidine (Chemical), cimetidine (Chemical), dementia (Disease), cimetidine (Chemical), cimetidine (Chemical), cimetidine (Chemical), dementia (Disease)


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

Input: Development of clear cell adenocarcinoma in DES-exposed offspring under observation. Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.

Output: Chemical/Disease Entities: clear cell adenocarcinoma (Disease), DES (Chemical), diethylstilbestrol (Chemical), carcinoma (Disease), carcinoma (Disease)


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

Input: Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis. The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial "calibrating" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.

Output: Chemical/Disease Entities: Phenobarbitone (Chemical), enlargement of the liver (Disease), carbon tetrachloride (Chemical), cirrhosis (Disease), cirrhosis of the liver (Disease), ascites (Disease), splenomegaly (Disease), atrophy (Disease), carbon tetrachloride (Chemical), phenobarbitone (Chemical), carbon tetrachloride (Chemical), phenobarbitone (Chemical), enlargement of the liver (Disease), CCl4 (Chemical), phenobarbitone (Chemical), carbon tetrachloride (Chemical), phenobarbitone (Chemical)


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

Input: Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats. The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.

Output: Chemical/Disease Entities: lithium (Chemical), diabetes-insipidus-like syndrome (Disease), amiloride (Chemical), amiloride (Chemical), lithium (Chemical), polydipsia (Disease), polyuria (Disease), lithium (Chemical), LiCl (Chemical), Amiloride (Chemical), amiloride (Chemical), lithium (Chemical), lithium (Chemical), lithium (Chemical), lithium (Chemical), diabetes-insipidus-like syndrome (Disease), amiloride (Chemical), lithium (Chemical), potassium (Chemical), amiloride (Chemical), lithium (Chemical), polydipsia (Disease), polyuria (Disease), amiloride (Chemical), lithium (Chemical)


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

Input: Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder. BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.

Output: Chemical/Disease Entities: alprazolam (Chemical), agoraphobia (Disease), panic disorder (Disease), benzodiazepines (Chemical), alprazolam (Chemical), panic disorder (Disease), agoraphobia (Disease), panic disorder (Disease), agoraphobia (Disease), alprazolam (Chemical), alprazolam (Chemical), alprazolam (Chemical), depression (Disease), enuresis (Disease), aggression (Disease), irritability (Disease), impaired memory (Disease), weight loss (Disease), ataxia (Disease), Alprazolam (Chemical)


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

Input: Dup 753 prevents the development of puromycin aminonucleoside-induced nephrosis. The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.

Output: Chemical/Disease Entities: Dup 753 (Chemical), puromycin aminonucleoside (Chemical), nephrosis (Disease), nephrotic syndromes (Disease), proteinuria (Disease), hypoalbuminemia (Disease), hypercholesterolemia (Disease), blood nitrogen urea (Chemical), puromycin aminonucleoside (Chemical), Dup 753 (Chemical), losartan (Chemical), angiotensin II (Chemical), angiotensin (Chemical), puromycin aminonucleoside (Chemical), nephrosis (Disease)


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

Input: Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction. In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.

Output: Chemical/Disease Entities: Sodium bicarbonate (Chemical), penile pain (Disease), erectile dysfunction (Disease), penile pain (Disease), penile pain (Disease), sodium bicarbonate (Chemical), impotence (Disease), papaverine (Chemical), phentolamine (Chemical), prostaglandin E1 (Chemical), sodium bicarbonate (Chemical), sodium bicarbonate (Chemical), penile pain (Disease), sodium bicarbonate (Chemical), penile pain (Disease), penile pain (Disease)


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

Input: Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients. This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.

Output: Chemical/Disease Entities: octreotide (Chemical), gallstone (Disease), acromegalic (Disease), acromegaly (Disease), octreotide (Chemical), octreotide (Chemical), gallstones (Disease), acute cholecystitis (Disease), depressed (Disease), octreotide (Chemical), gallstones (Disease), gallstones (Disease), depressed (Disease), gallstones (Disease), cholecystitis (Disease), octreotide (Chemical), acromegalic (Disease), octreotide (Chemical), acromegalic (Disease)


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Input: Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease. Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.

Output: Chemical/Disease Entities: levodopa (Chemical), dyskinesia (Disease), propranolol (Chemical), Parkinson's disease (Disease), Parkinson's disease (Disease), PD (Disease), dyskinesia (Disease), propranolol (Chemical), dyskinesia (Disease), parkinsonian (Disease), motor disability (Disease), dyskinesia (Disease), dystonia (Disease), levodopa (Chemical), dyskinesia (Disease), PD (Disease)


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

Input: Morphological features of encephalopathy after chronic administration of the antiepileptic drug valproate to rats. A transmission electron microscopic study of capillaries in the cerebellar cortex. Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral "Polfa") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage ("valproate encephalopathy"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.

Output: Chemical/Disease Entities: encephalopathy (Disease), valproate (Chemical), sodium valproate (Chemical), neurological disorders (Disease), cerebellum damage (Disease), valproate (Chemical), encephalopathy (Disease), necrosis (Disease), luminal (Chemical), necrotic (Disease), luminal (Chemical), hepatic damage (Disease), hyperammonemia (Disease), valproate (Chemical), encephalopathy (Disease)


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Input: Macula toxicity after intravitreal amikacin. BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.

Output: Chemical/Disease Entities: toxicity (Disease), amikacin (Chemical), aminoglycosides (Chemical), endophthalmitis (Disease), infarction (Disease), amikacin (Chemical), retinal toxicity (Disease), amikacin (Chemical), vancomycin (Chemical), streptococcal endophthalmitis (Disease), Endophthalmitis (Disease), fluorescein (Chemical), telangiectasis (Disease), retinal toxicity (Disease), ischaemia (Disease), retinal toxicity (Disease)


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

Input: Iatrogenically induced intractable atrioventricular reentrant tachycardia after verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome and idiopathic dilated cardiomyopathy. In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS without preexcitation, caused by junctional escape beats after verapamil or unidirectional antegrade block of accessory pathway after catheter ablation, established frequent AVRT attack.

Output: Chemical/Disease Entities: atrioventricular reentrant tachycardia (Disease), verapamil (Chemical), Wolff-Parkinson-White syndrome (Disease), idiopathic dilated cardiomyopathy (Disease), WPW syndrome (Disease), idiopathic dilated cardiomyopathy (Disease), atrioventricular reentrant tachycardia (Disease), AVRT (Disease), verapamil (Chemical), AVRT (Disease)


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

Input: Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons. BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.

Output: Chemical/Disease Entities: liver disease (Disease), hydrochlorofluorocarbons (Chemical), ozone (Chemical), chlorofluorocarbons (Chemical), Hydrochlorofluorocarbons (Chemical), HCFCs (Chemical), ozone (Chemical), chlorofluorocarbons (Chemical), CFCs (Chemical), hepatotoxicity (Disease), liver disease (Disease), 1,1-dichloro-2,2,2-trifluoroethane (Chemical), HCFC 123 (Chemical), 1-chloro-1,2,2,2-tetrafluoroethane (Chemical), HCFC 124 (Chemical), 1-bromo-1-chloro-2,2,2-trifluoroethane (Chemical), halothane (Chemical), trifluoroacetyl (Chemical), hepatotoxicity (Disease), halothane (Chemical), liver disease (Disease), trifluoroacetyl (Chemical), necrosis (Disease), necrosis (Disease), Trifluoroacetyl (Chemical), halothane hepatitis (Disease), liver injury (Disease), hepatotoxicity (Disease), trifluoroacetyl (Chemical)


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

Input: The effect of different anaesthetic agents in hearing loss following spinal anaesthesia. The cause of hearing loss after spinal anaesthesia is unknown. Up until now, the only factor studied has been the effect of the diameter of the spinal needle on post-operative sensorineural hearing loss. The aim of this study was to describe this hearing loss and to investigate other factors influencing the degree of hearing loss. Two groups of 22 similar patients were studied: one group received 6 mL prilocaine 2%; and the other received 3 mL bupivacaine 0.5%. Patients given prilocaine were more likely to develop hearing loss (10 out of 22) than those given bupivacaine (4 out of 22) (P < 0.05). The average hearing loss for speech frequencies was about 10 dB after prilocaine and 15 dB after bupivacaine. None of the patients complained of subjective hearing loss. Long-term follow-up of the patients was not possible.

Output: Chemical/Disease Entities: hearing loss (Disease), hearing loss (Disease), sensorineural hearing loss (Disease), hearing loss (Disease), hearing loss (Disease), prilocaine (Chemical), bupivacaine (Chemical), prilocaine (Chemical), hearing loss (Disease), bupivacaine (Chemical), hearing loss (Disease), prilocaine (Chemical), bupivacaine (Chemical), hearing loss (Disease)


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

Input: A transient neurological deficit following intrathecal injection of 1% hyperbaric bupivacaine for unilateral spinal anaesthesia. We describe a case of transient neurological deficit that occurred after unilateral spinal anaesthesia with 8 mg of 1% hyperbaric bupivacaine slowly injected through a 25-gauge pencil-point spinal needle. The surgery and anaesthesia were uneventful, but 3 days after surgery, the patient reported an area of hypoaesthesia over L3-L4 dermatomes of the leg which had been operated on (loss of pinprick sensation) without reduction in muscular strength. Sensation in this area returned to normal over the following 2 weeks. Prospective multicentre studies with a large population and a long follow-up should be performed in order to evaluate the incidence of this unusual side effect. However, we suggest that a low solution concentration should be preferred for unilateral spinal anaesthesia with a hyperbaric anaesthetic solution (if pencil-point needle and slow injection rate are employed), in order to minimize the risk of a localized high peak anaesthetic concentration, which might lead to a transient neurological deficit.

Output: Chemical/Disease Entities: neurological deficit (Disease), bupivacaine (Chemical), neurological deficit (Disease), bupivacaine (Chemical), loss of pinprick sensation (Disease), neurological deficit (Disease)


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

Input: Pethidine-associated seizure in a healthy adolescent receiving pethidine for postoperative pain control. A healthy 17-year-old male received standard intermittent doses of pethidine via a patient-controlled analgesia (PCA) pump for management of postoperative pain control. Twenty-three h postoperatively he developed a brief self-limited seizure. Both plasma pethidine and norpethidine were elevated in the range associated with clinical manifestations of central nervous system excitation. No other risk factors for CNS toxicity were identified. This method allowed frequent self-dosing of pethidine at short time intervals and rapid accumulation of pethidine and norpethidine. The routine use of pethidine via PCA even for a brief postoperative analgesia should be reconsidered.

Output: Chemical/Disease Entities: Pethidine (Chemical), seizure (Disease), pethidine (Chemical), postoperative pain (Disease), pethidine (Chemical), postoperative pain (Disease), seizure (Disease), pethidine (Chemical), norpethidine (Chemical), toxicity (Disease), pethidine (Chemical), pethidine (Chemical), norpethidine (Chemical), pethidine (Chemical)


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

Input: Drug-associated acute-onset vanishing bile duct and Stevens-Johnson syndromes in a child. Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.

Output: Chemical/Disease Entities: vanishing bile duct (Disease), Stevens-Johnson syndromes (Disease), vanishing bile duct (Disease), cholestasis (Disease), Stevens-Johnson syndrome (Disease), hypersensitivity (Disease), infection (Disease), vanishing bile duct syndrome (Disease), Stevens-Johnson syndrome (Disease), ibuprofen (Chemical), ursodeoxycholic acid (Chemical), prednisone (Chemical), tacrolimus (Chemical), cholestatic disease (Disease), cirrhosis (Disease), vanishing bile duct syndrome (Disease), Stevens-Johnson syndrome (Disease), vanishing bile duct syndrome (Disease)


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

Input: High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium. Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.

Output: Chemical/Disease Entities: primary pulmonary hypertension (Disease), appetite suppressants (Chemical), Primary pulmonary hypertension (Disease), appetite suppressant (Chemical), appetite suppressants (Chemical), primary pulmonary hypertension (Disease), appetite-suppressants (Chemical), appetite suppressants (Chemical), fenfluramines (Chemical), appetite suppressants (Chemical), primary pulmonary hypertension (Disease), appetite suppressants (Chemical), appetite suppressants (Chemical), appetite suppressants (Chemical), primary pulmonary hypertension (Disease), appetite suppressants (Chemical)


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

Input: Choreoathetoid movements associated with rapid adjustment to methadone. Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.

Output: Chemical/Disease Entities: Choreoathetoid movements (Disease), methadone (Chemical), movement abnormalities (Disease), cocaine (Chemical), choreoathetoid movements (Disease), methadone (Chemical), heroine (Chemical), cocaine (Chemical)


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

Input: Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample. This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.

Output: Chemical/Disease Entities: Cocaine (Chemical), mood disorder (Disease), psychiatric (Disease), cocaine (Chemical), mood disorders (Disease), cocaine (Chemical), cocaine (Chemical), mood disorder (Disease), CIMD (Disease), mood disorders (Disease), mood disorder (Disease), psychiatric (Disease), CIMD (Disease), CIMD (Disease), depressive disorders (Disease), CIMD (Disease), mood disorder (Disease), CIMD (Disease)


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

Input: Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure. Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.

Output: Chemical/Disease Entities: Hemolysis (Disease), tamoxifen (Chemical), Tamoxifen (Chemical), TAM (Chemical), breast cancer (Disease), hemolytic anemia (Disease), TAM (Chemical), TAM (Chemical), hemolytic anemia (Disease), TAM (Chemical), hemolysis (Disease), hemolysis (Disease), TAM (Chemical), hemolysis (Disease), TAM (Chemical), hemolytic (Disease), TAM (Chemical), alpha-tocopherol (Chemical), alpha-T (Chemical), alpha-tocopherol acetate (Chemical), alpha-TAc (Chemical), hydroxyl (Chemical), TAM (Chemical), hemolysis (Disease), oxygen (Chemical), TAM (Chemical), hemolysis (Disease), TAM (Chemical), AAPH (Chemical), TAM (Chemical), Hemolysis (Disease), TAM (Chemical), K (Chemical), hemolysis (Disease), TAM (Chemical), alpha-T (Chemical), alpha-TAc (Chemical), TAM (Chemical), hemolysis (Disease), tocopherols (Chemical), TAM (Chemical), TAM (Chemical), hemolysis (Disease), TAM (Chemical), hemolytic anemia (Disease), TAM (Chemical)


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

Input: Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension. In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.

Output: Chemical/Disease Entities: sodium (Chemical), ATP (Chemical), Na (Chemical), K (Chemical), nitric oxide (Chemical), hypertension (Disease), NO (Chemical), NO (Chemical), hypertension (Disease), hypertension (Disease), sodium (Chemical), Na (Chemical), Na (Chemical), K (Chemical), NO (Chemical), hypertension (Disease), NO (Chemical), N(G)-nitro-L-arginine methyl ester (Chemical), L-NAME (Chemical), L-NAME (Chemical), Na (Chemical), K (Chemical), ATP (Chemical), NO (Chemical), Na (Chemical), K (Chemical), Na (Chemical), Na (Chemical), NO (Chemical), hypertension (Disease), Na (Chemical), K (Chemical), ATP (Chemical), ATP (Chemical), K (Chemical), Na (Chemical), Na (Chemical), NO (Chemical), hypertension (Disease), depressed (Disease), Na (Chemical), Na (Chemical), Na (Chemical), K (Chemical), Na (Chemical), Na (Chemical), K (Chemical)