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

Input: Effects of 5-HT1B receptor ligands microinjected into the accumbal shell or core on the cocaine-induced locomotor hyperactivity in rats. The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 microg/side) or CP 93129 (0.1-10 microg/side) did not change basal locomotor activity. Systemic cocaine (10 mg/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 microg/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 microg/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 microg/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 microg/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant.

Output: Chemical/Disease Entities: cocaine (Chemical), locomotor hyperactivity (Disease), locomotor hyperactivity (Disease), cocaine (Chemical), GR 55562 (Chemical), CP 93129 (Chemical), GR 55562 (Chemical), CP 93129 (Chemical), cocaine (Chemical), GR 55562 (Chemical), cocaine (Chemical), locomotor hyperactivity (Disease), GR 55562 (Chemical), cocaine (Chemical), CP 93129 (Chemical), cocaine (Chemical), GR 55562 (Chemical), cocaine (Chemical), hyperlocomotion (Disease), GR 55562 (Chemical), CP 93129 (Chemical)


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

Input: Ticlopidine-induced cholestatic hepatitis. OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.

Output: Chemical/Disease Entities: Ticlopidine (Chemical), ticlopidine (Chemical), ticlopidine (Chemical), ticlopidine (Chemical), ticlopidine (Chemical), jaundice (Disease), ticlopidine (Chemical), Hepatitis (Disease), ticlopidine (Chemical), ticlopidine (Chemical), cholestasis (Disease), hepatotoxicity (Disease), ticlopidine (Chemical), ticlopidine (Chemical), clopidogrel (Chemical)


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

Input: Epithelial sodium channel (ENaC) subunit mRNA and protein expression in rats with puromycin aminonucleoside-induced nephrotic syndrome. In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.

Output: Chemical/Disease Entities: sodium (Chemical), puromycin aminonucleoside (Chemical), nephrotic syndrome (Disease), nephrotic syndrome (Disease), sodium (Chemical), sodium (Chemical), sodium (Chemical), puromycin aminonucleoside (Chemical), PAN (Chemical), nephrotic syndrome (Disease), sodium (Chemical), aldosterone (Chemical), proteinuria (Disease), PAN (Chemical), sodium (Chemical), proteinuria (Disease), Sodium (Chemical), PAN (Chemical), sodium (Chemical), aldosterone (Chemical), sodium (Chemical), PAN (Chemical), sodium (Chemical), PAN (Chemical), nephrotic syndrome (Disease), aldosterone (Chemical)


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

Input: NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release. The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.

Output: Chemical/Disease Entities: NO (Chemical), migraine (Disease), calcitonin gene-related peptide (Chemical), CGRP (Chemical), serotonin (Chemical), calcitonin gene-related peptide (Chemical), CGRP (Chemical), serotonin (Chemical), 5-hydroxytriptamine (Chemical), 5-HT (Chemical), headache (Disease), migraine (Disease), nitroglycerin (Chemical), migraineurs (without aura) (Disease), nitroglycerin (Chemical), nitroglycerin (Chemical), migraine (Disease), migraine (Disease), CGRP (Chemical), migraine (Disease), migraine (Disease), migraine (Disease), headache (Disease), CGRP (Chemical), headache (Disease), migraine (Disease), CGRP (Chemical), 5-HT (Chemical), migraine (Disease), serotonin (Chemical), nitroglycerin (Chemical), migraine (Disease), migraine (Disease), CGRP (Chemical), migraine (Disease), headache (Disease), CGRP (Chemical), migraine (Disease), serotonin (Chemical), migraine (Disease), headache (Disease), CGRP (Chemical)


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

Input: Coronary aneurysm after implantation of a paclitaxel-eluting stent. Formation of coronary aneurysm is a rare complication of stenting with bare metal stents, but based on experimental studies drug-eluting stents may induce toxic effects on the vessel wall with incomplete stent apposition, aneurysm formation and with the potential of stent thrombosis or vessel rupture. We present a 43-year-old man who developed a coronary aneurysm in the right coronary artery 6 months after receiving a paclitaxel-eluting stent. The patient was asymptomatic and the aneurysm was detected in a routine control. Angiography and intracoronary ultrasound demonstrated lack of contact between stent and vessel wall in a 15-mm long segment with maximal aneurysm diameter of 6.0 mm. The patient was successfully treated with a graft stent.

Output: Chemical/Disease Entities: Coronary aneurysm (Disease), paclitaxel (Chemical), coronary aneurysm (Disease), aneurysm (Disease), thrombosis (Disease), vessel rupture (Disease), coronary aneurysm (Disease), paclitaxel (Chemical), aneurysm (Disease), aneurysm (Disease)


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

Input: Behavioral effects of urotensin-II centrally administered in mice. Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.

Output: Chemical/Disease Entities: urotensin-II (Chemical), Urotensin-II (Chemical), U-II (Chemical), U-II (Chemical), hypertension (Disease), bradycardia (Disease), U-II (Chemical), U-II (Chemical), U-II (Chemical), U-II (Chemical), U-II (Chemical), apomorphine (Chemical), penile erection (Disease), corticosterone (Chemical), U-II (Chemical), U-II (Chemical), psychiatric disorders (Disease)


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

Input: Recurrent dysphonia and acitretin. We report the case of a woman complaining of dysphonia while she was treated by acitretin. Her symptoms totally regressed after drug withdrawal and reappeared when acitretin was reintroduced. To our knowledge, this is the first case of acitretin-induced dysphonia. This effect may be related to the pharmacological effect of this drug on mucous membranes.

Output: Chemical/Disease Entities: dysphonia (Disease), acitretin (Chemical), dysphonia (Disease), acitretin (Chemical), acitretin (Chemical), acitretin (Chemical), dysphonia (Disease)


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

Input: Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans. Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.

Output: Chemical/Disease Entities: pain (Disease), pain (Disease), tissue injury (Disease), secondary hyperalgesia (Disease), Secondary hyperalgesia (Disease), neurogenic hyperalgesia (Disease), neuropathic pain (Disease), hyperalgesia (Disease), gabapentin (Chemical), neuropathic pain (Disease), gabapentin (Chemical), capsaicin (Chemical), secondary hyperalgesia (Disease), gabapentin (Chemical), gabapentin (Chemical), gabapentin (Chemical), gabapentin (Chemical), gabapentin (Chemical), gabapentin (Chemical)


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

Input: MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes. In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on "prefrontal" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.

Output: Chemical/Disease Entities: MDMA (Chemical), impaired social and emotional judgement processes (Disease), memory deficits (Disease), MDMA (Chemical), 3,4-methylenedioxymethamphetamine (Chemical), ecstasy (Chemical), MDMA (Chemical), ecstasy (Chemical), ecstasy (Chemical), MDMA (Chemical), MDMA (Chemical), ecstasy (Chemical)


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

Input: Severe citrate toxicity complicating volunteer apheresis platelet donation. We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.

Output: Chemical/Disease Entities: citrate (Chemical), toxicity (Disease), citrate (Chemical), toxicity (Disease), hypertension (Disease), hyperlipidemia (Disease), depression (Disease), bumetanide (Chemical), pravastatin (Chemical), paroxetine (Chemical), tetany (Disease), calcium gluconate (Chemical), muscle contractions (Disease), calcium (Chemical), sodium citrate (Chemical), hypocalcemia (Disease), bumetanide (Chemical), loop diuretic (Chemical), hypocalcemia (Disease), hypocalcemia (Disease), citrate (Chemical), toxicity (Disease), calcium (Chemical)


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

Input: Proteinuria after conversion to sirolimus in renal transplant recipients. Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.

Output: Chemical/Disease Entities: Proteinuria (Disease), sirolimus (Chemical), Sirolimus (Chemical), SRL (Chemical), proteinuria (Disease), sirolimus (Chemical), proteinuria (Disease), SRL (Chemical), SRL (Chemical), chronic allograft nephropathy (Disease), CAN (Disease), neoplasia (Disease), Kaposi's sarcoma (Disease), skin cancers (Disease), intestinal tumors (Disease), renal cell carsinom (Disease), nephropathy (Disease), SRL (Chemical), SRL (Chemical), Proteinuria (Disease), proteinuria (Disease), proteinuria (Disease), proteinuria (Disease), proteinuria (Disease), nephrotic (Disease), membranoproliferative glomerulopathy (Disease), interstitial nephritis (Disease), creatinine (Chemical), SRL (Chemical), CAN (Disease), Kaposi's sarcoma (Disease), creatinine (Chemical), proteinuria (Disease), SRL (Chemical), CAN (Disease), proteinuria (Disease), SRL (Chemical)


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

Input: In vitro characterization of parasympathetic and sympathetic responses in cyclophosphamide-induced cystitis in the rat. In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.

Output: Chemical/Disease Entities: cyclophosphamide (Chemical), cystitis (Disease), cyclophosphamide (Chemical), cystitis (Disease), cystitis (Disease), cyclophosphamide (Chemical), atropine (Chemical), alpha,beta-methylene adenosine-5'-triphosphate (Chemical), alpha,beta-meATP (Chemical), atropine (Chemical), 4-diphenylacetoxy-N-methylpiperidine (Chemical), 4-DAMP (Chemical), methoctramine (Chemical), pirenzepine (Chemical), 4-DAMP (Chemical), methoctramine (Chemical), pirenzepine (Chemical), pirenzepine (Chemical), 4-DAMP (Chemical), methoctramine (Chemical), carbachol (Chemical), ATP (Chemical), potassium (Chemical), isoprenaline (Chemical), cystitis (Disease)


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

Input: Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly. OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.

Output: Chemical/Disease Entities: benzodiazepines (Chemical), benzodiazepines (Chemical), BZDs (Chemical), BZDs (Chemical), BZDs (Chemical), oxazepam (Chemical), temazepam (Chemical), zopiclone (Chemical), BZDs (Chemical), dementia (Disease), BZDs (Chemical), BZDs (Chemical), dizziness (Disease), inability to sleep (Disease), tiredness (Disease), depressive symptoms (Disease), BZDs (Chemical), temazepam (Chemical)


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

Input: Acute vocal fold palsy after acute disulfiram intoxication. Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.

Output: Chemical/Disease Entities: vocal fold palsy (Disease), disulfiram (Chemical), peripheral neuropathy (Disease), disulfiram (Chemical), overdose (Disease), vocal fold palsy (Disease), quadriparesis (Disease), pain (Disease), sensory loss (Disease), paresthesia (Disease), disulfiram (Chemical), ALCOHOL (Chemical), ataxia (Disease), giddiness (Disease), hoarseness (Disease), polyneuropathy (Disease), palsy (Disease), polyneuropathy (Disease), disulfiram (Chemical)


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

Input: Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia. OBJECTIVES: To correlate optical density and percent inhibition of a two-step heparin-induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. PATIENTS AND METHODS: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 x 10(9)/L) after exposure to heparin, who had a positive two-step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. RESULTS: Forty of 94 HIT patients had thrombosis at diagnosis; 54/94 had isolated-HIT without thrombosis. Eight of the isolated-HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated-HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 +/- 0.89), including isolated-HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 +/- 0.64) as compared to isolated-HIT patients who did not develop thrombosis (0.96 +/- 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated-HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8-fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. CONCLUSION: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated-HIT; percent inhibition, however, was not predictive.

Output: Chemical/Disease Entities: thrombosis (Disease), heparin (Chemical), thrombocytopenia (Disease), heparin (Chemical), thrombocytopenia (Disease), HIT (Disease), thrombosis (Disease), heparin (Chemical), thrombocytopenia (Disease), heparin (Chemical), heparin (Chemical), HIT (Disease), thrombosis (Disease), HIT (Disease), thrombosis (Disease), HIT (Disease), thrombosis (Disease), thrombosis (Disease), HIT (Disease), thrombosis (Disease), HIT (Disease), thrombosis (Disease), HIT (Disease), thrombosis (Disease), HIT (Disease), thrombosis (Disease), HIT (Disease), thrombosis (Disease), thrombosis (Disease), thrombotic (Disease), thrombosis (Disease), HIT (Disease)


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

Input: Central retinal vein occlusion associated with clomiphene-induced ovulation. OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.

Output: Chemical/Disease Entities: retinal vein occlusion (Disease), clomiphene (Chemical), retinal vein occlusion (Disease), clomiphene citrate (Chemical), CC (Chemical), infertility (Disease), blurred vision (Disease), CC (Chemical), retinal vein occlusion (Disease), CC (Chemical), retinal vein occlusion (Disease), CC (Chemical), thromboembolic (Disease), CC (Chemical), visual disturbance (Disease), CC (Chemical), retinal vein occlusion (Disease), CC (Chemical), infertility (Disease), CC (Chemical)


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

Input: Nicotine-induced nystagmus correlates with midpontine activation. The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements.

Output: Chemical/Disease Entities: Nicotine (Chemical), nystagmus (Disease), nicotine (Chemical), nystagmus (Disease), NIN (Disease), NIN (Disease), nicotine (Chemical), NIN (Disease), oxygen (Chemical), NIN (Disease)


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

Input: Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats. Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.

Output: Chemical/Disease Entities: verapamil (Chemical), gastric hemorrhagic (Disease), ulcers (Disease), atherosclerotic (Disease), gastric hemorrhage (Disease), atherosclerotic (Disease), histamine (Chemical), gastric hemorrhage (Disease), ulcer (Disease), atherosclerosis (Disease), vitamin D2 (Chemical), cholesterol (Chemical), verapamil (Chemical), ulcer (Disease), vitamin D2 (Chemical), cholesterol (Chemical), atherosclerosis (Disease), histamine (Chemical), luminal (Chemical), ulcer (Disease), atherosclerotic (Disease), calcium (Chemical), cholesterol (Chemical), atherosclerotic (Disease), ulcers (Disease), histamine (Chemical), luminal (Chemical), histamine (Chemical), gastric hemorrhage (Disease), ulcer (Disease), atherosclerotic (Disease), hemorrhagic (Disease), ulcer (Disease), verapamil (Chemical), Atherosclerosis (Disease), gastric hemorrhagic (Disease), ulcer (Disease), histamine (Chemical), verapamil (Chemical)


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

Input: Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure. BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure. METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model. RESULTS: 3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles. CONCLUSION: Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway.

Output: Chemical/Disease Entities: Adriamycin (Chemical), death (Disease), heart failure (Disease), heart failure (Disease), adriamycin (Chemical), heart failure (Disease), adriamycin (Chemical), heart failure (Disease), 3-methyladenine (Chemical), 3MA (Chemical), heart failure (Disease), adriamycin (Chemical), adriamycin (Chemical), 3MA (Chemical), adriamycin (Chemical), K (Chemical), 3MA (Chemical), adriamycin (Chemical), 3MA (Chemical), adriamycin (Chemical), death (Disease), heart failure (Disease), adriamycin (Chemical), heart failure (Disease), adriamycin (Chemical)


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

Input: Confusion, a rather serious adverse drug reaction with valproic acid: a review of the French Pharmacovigilance database. INTRODUCTION: Confusion is an adverse drug reaction frequently observed with valproic acid. Some case reports are published in the literature but no systematic study from a sample of patients has been published. We performed this study in order to describe the main characteristics of this adverse drug reaction. METHODS: Using the French Pharmacovigilance database, we selected the cases of confusion reported since 1985 with valproic acid. RESULTS: 272 cases of confusion were reported with valproic acid: 153 women and 119 men. Confusion mostly occurred during the two first weeks following valproic acid exposure (39.7%). It was "serious" for almost 2/3 of the patients (62.5%) and its outcome favourable in most of the cases (82%). The occurrence of this ADR was more frequent in patients aged between 61 and 80 years. CONCLUSION: This work shows that confusion with valproic acid is a serious, rather frequent but reversible adverse drug reaction. It occurs especially in older patients and during the first two weeks of treatment.

Output: Chemical/Disease Entities: Confusion (Disease), valproic acid (Chemical), Confusion (Disease), valproic acid (Chemical), confusion (Disease), valproic acid (Chemical), confusion (Disease), valproic acid (Chemical), Confusion (Disease), valproic acid (Chemical), confusion (Disease), valproic acid (Chemical)


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

Input: Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task. It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.

Output: Chemical/Disease Entities: ecstasy (Chemical), ecstasy (Chemical), ecstasy (Chemical), ecstasy (Chemical), cannabis (Chemical), ecstasy (Chemical), cannabis (Chemical), hyperactivity (Disease), cannabis (Chemical), Ecstasy (Chemical), cannabis (Chemical), ecstasy (Chemical), hyperactivity (Disease), Ecstasy (Chemical), ecstasy (Chemical), cannabis (Chemical), ecstasy (Chemical), cannabis (Chemical), ecstasy (Chemical), neurotoxic (Disease), ecstasy (Chemical)


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

Input: Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis. BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.

Output: Chemical/Disease Entities: argatroban (Chemical), heparin (Chemical), thrombocytopenia (Disease), thrombosis (Disease), heparin (Chemical), thrombocytopenia (Disease), HIT (Disease), HIT (Disease), thrombosis (Disease), HITT (Disease), critically ill (Disease), HITT (Disease), argatroban (Chemical), argatroban (Chemical), argatroban (Chemical), argatroban (Chemical), hepatic impairment (Disease), argatroban (Chemical), argatroban (Chemical), coagulopathy (Disease), argatroban (Chemical), coagulopathy (Disease)


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

Input: Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome. Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.

Output: Chemical/Disease Entities: Antituberculosis (Chemical), acute liver failure (Disease), Antituberculosis (Chemical), acute liver failure (Disease), ALF (Disease), ALF (Disease), ALF (Disease), ALF (Disease), ALF (Disease), hepatitis virus infection (Disease), tuberculosis (Disease), ALF (Disease), icterus (Disease), encephalopathy (Disease), ALF (Disease), encephalopathy (Disease), cerebral edema (Disease), Gastrointestinal bleed (Disease), seizures (Disease), infection (Disease), acute renal failure (Disease), hepatitis E (Disease), ALF (Disease), ALF (Disease), ALF (Disease), bilirubin (Chemical), encephalopathy (Disease), ALF (Disease), ALF (Disease)


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

Input: Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution. Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.

Output: Chemical/Disease Entities: Central nervous system complications (Disease), acute lymphoblastic leukemia (Disease), Central nervous system (CNS) complications (Disease), acute lymphoblastic leukemia (Disease), ALL (Disease), neurological complications (Disease), ALL (Disease), leukemic infiltration (Disease), peripheral neuropathy (Disease), encephalopathy (Disease), neurocognitive defects (Disease), ALL (Disease), leukoencephalopathy (Disease), stroke (Disease), temporal lobe epilepsy (Disease), methotrexate (Chemical), toxicity (Disease), inappropriate antidiuretic hormone secretion (Disease), ALL (Disease)


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

Input: Safety of capecitabine: a review. IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.

Output: Chemical/Disease Entities: capecitabine (Chemical), Fluoropyrimidines (Chemical), 5-fluorouracil (Chemical), 5-FU (Chemical), tumors (Disease), capecitabine (Chemical), capecitabine (Chemical), renal and kidney disease (Disease), capecitabine (Chemical), Capecitabine (Chemical), 5-FU (Chemical), capecitabine (Chemical), diarrhea (Disease), nausea (Disease), vomiting (Disease), stomatitis (Disease), hand-foot syndrome (Disease), Capecitabine (Chemical)


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

Input: Effects of pallidal neurotensin on haloperidol-induced parkinsonian catalepsy: behavioral and electrophysiological studies. OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects.

Output: Chemical/Disease Entities: neurotensin (Chemical), haloperidol (Chemical), parkinsonian catalepsy (Disease), neurotensin (Chemical), neurotensin (Chemical), haloperidol (Chemical), parkinsonian symptoms (Disease), neurotensin (Chemical), haloperidol (Chemical), parkinsonian catalepsy (Disease), neurotensin (Chemical), haloperidol (Chemical), neurotensin type-1 receptor antagonist (Chemical), SR48692 (Chemical), neurotensin (Chemical), neurotensin (Chemical), neurotensin (Chemical)


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

Input: Antihypertensive drugs and depression: a reappraisal. Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories.

Output: Chemical/Disease Entities: depression (Disease), hypertensive (Disease), hypertensive (Disease), depression (Disease), hypertensive (Disease), Hypertensive (Disease), psychiatric (Disease), depression (Disease), depressions (Disease), methyl dopa (Chemical), psychiatric (Disease)


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

Input: Pulmonary shunt and cardiovascular responses to CPAP during nitroprusside-induced hypotension. The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS/QT, produce marked decreases in arterial blood pressure and cardiac output.

Output: Chemical/Disease Entities: nitroprusside (Chemical), hypotension (Disease), sodium nitroprusside (Chemical), nitroprusside (Chemical), H2O (Chemical), H2O (Chemical), nitroprusside (Chemical), decrease in arterial blood pressure (Disease), decreased cardiac output (Disease), Nitroprusside (Chemical), decreases in arterial blood pressure (Disease), H2O (Chemical), nitroprusside (Chemical), H2O (Chemical), nitroprusside (Chemical), nitroprusside (Chemical), H2O (Chemical)


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

Input: Mediation of enhanced reflex vagal bradycardia by L-dopa via central dopamine formation in dogs. L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.

Output: Chemical/Disease Entities: bradycardia (Disease), L-dopa (Chemical), dopamine (Chemical), L-Dopa (Chemical), MK-486 (Chemical), MAO (Chemical), bradycardia (Disease), norepinephrine (Chemical), L-dopa (Chemical), DL-Threo-dihydroxyphenylserine (Chemical), norepinephrine (Chemical), FLA-63 (Chemical), dopamine (Chemical), hypotension (Disease), bradycardia (Disease), L-dopa (Chemical), Pimozide (Chemical), L-dopa (Chemical), norepinephrine (Chemical), L-dopa (Chemical), bradycardia (Disease), norepinephrine (Chemical), 5-HTP (Chemical), bradycardia (Disease), norepinephrine (Chemical), L-dopa (Chemical), bradycardia (Disease), dopamine (Chemical), norepinephrine (Chemical)


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

Input: Cocaine-induced myocardial infarction: clinical observations and pathogenetic considerations. Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.

Output: Chemical/Disease Entities: Cocaine (Chemical), myocardial infarction (Disease), cocaine (Chemical), acute myocardial infarction (Disease), acute myocardial infarction (Disease), oxygen (Chemical), cocaine (Chemical), atherosclerotic obstruction (Disease), coronary occlusion (Disease), spasm (Disease), thrombus (Disease), spasm (Disease), cocaine (Chemical), spasm (Disease), infarction (Disease), cocaine (Chemical), thrombotic (Disease), cocaine (Chemical)


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

Input: Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings. The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved.

Output: Chemical/Disease Entities: Rabbit syndrome (Disease), antidepressant (Chemical), rabbit syndrome (Disease), imipramine (Chemical), antidepressants (Chemical), decreased basal ganglia perfusion (Disease), movement disorder (Disease), rabbit syndrome (Disease)


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

Input: Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease. The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.

Output: Chemical/Disease Entities: ipratropium bromide (Chemical), theophylline (Chemical), chronic obstructive pulmonary disease (Disease), ipratropium bromide (Chemical), theophylline (Chemical), chronic obstructive pulmonary disease (Disease), ipratropium (Chemical), theophylline (Chemical), ipratropium (Chemical), theophylline (Chemical), ipratropium (Chemical), theophylline (Chemical), theophylline (Chemical), ipratropium (Chemical), theophylline (Chemical), chronic airflow obstruction (Disease)


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

Input: Irreversible damage to the medullary interstitium in experimental analgesic nephropathy in F344 rats. Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla.

Output: Chemical/Disease Entities: nephropathy (Disease), Renal papillary necrosis (Disease), RPN (Disease), aspirin (Chemical), paracetamol (Chemical), RPN (Disease)


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

Input: Less frequent lithium administration and lower urine volume. OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.

Output: Chemical/Disease Entities: lithium (Chemical), lithium (Chemical), lithium (Chemical), lithium (Chemical), creatinine (Chemical), lithium (Chemical), lithium (Chemical), lithium (Chemical), creatinine (Chemical), lithium (Chemical), Lithium (Chemical), polyuria (Disease)


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

Input: Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues. Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for "acute" hematological changes were 1.3, whereas those estimated for "late" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.

Output: Chemical/Disease Entities: adriamycin (Chemical), hyperthermia (Disease), tumor (Disease), Adriamycin (Chemical), toxicities (Disease), hyperthermia (Disease), tumor (Disease), toxicities (Disease), leukopenia (Disease), thrombocytopenia (Disease), toxicities (Disease), hyperthermia (Disease), Adriamycin (Chemical), hyperthermia (Disease), Adriamycin (Chemical), toxicity (Disease)


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

Input: Prazosin-induced stress incontinence. A case of genuine stress incontinence due to prazosin, a common antihypertensive drug, is presented. Prazosin exerts its antihypertensive effects through vasodilatation caused by selective blockade of postsynaptic alpha-1 adrenergic receptors. As an alpha-blocker, it also exerts a significant relaxant effect on the bladder neck and urethra. The patient's clinical course is described and correlated with initial urodynamic studies while on prazosin and subsequent studies while taking verapamil. Her incontinence resolved with the change of medication. The restoration of continence was accompanied by a substantial rise in maximum urethral pressure, maximum urethral closure pressure, and functional urethral length. Patients who present with stress incontinence while taking prazosin should change their antihypertensive medication before considering surgery, because their incontinence may resolve spontaneously with a change in drug therapy.

Output: Chemical/Disease Entities: Prazosin (Chemical), stress incontinence (Disease), stress incontinence (Disease), prazosin (Chemical), Prazosin (Chemical), prazosin (Chemical), verapamil (Chemical), incontinence (Disease), stress incontinence (Disease), prazosin (Chemical), incontinence (Disease)


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

Input: Myocardial infarction following sublingual administration of isosorbide dinitrate. A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.

Output: Chemical/Disease Entities: Myocardial infarction (Disease), isosorbide dinitrate (Chemical), necrosis (Disease), myocardial infarction (Disease), isosorbide dinitrate (Chemical), spasm (Disease), hypotension (Disease), myocardial ischemia (Disease), coronary arterial stenosis (Disease), acute coronary insufficiency (Disease)


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

Input: Fluoxetine-induced akathisia: clinical and theoretical implications. Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced "jitteriness" may be identical.

Output: Chemical/Disease Entities: Fluoxetine (Chemical), akathisia (Disease), fluoxetine (Chemical), obsessive compulsive disorder (Disease), major depression (Disease), akathisia (Disease), fluoxetine (Chemical), anxiety (Disease), akathisia (Disease), akathisia (Disease), fluoxetine (Chemical), akathisia (Disease), Akathisia (Disease), fluoxetine (Chemical), propranolol (Chemical), fluoxetine (Chemical), akathisia (Disease), fluoxetine (Chemical), akathisia (Disease), antidepressant (Chemical)


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

Input: Chronic active hepatitis associated with diclofenac sodium therapy. Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.

Output: Chemical/Disease Entities: Chronic active hepatitis (Disease), diclofenac sodium (Chemical), Diclofenac sodium (Chemical), Voltarol (Chemical), phenylacetic acid (Chemical), abnormalities of liver function (Disease), hepatitis (Disease), diclofenac (Chemical), chronic active hepatitis (Disease), diclofenac sodium (Chemical)


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

Input: Stroke associated with cocaine use. We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.

Output: Chemical/Disease Entities: Stroke (Disease), cocaine (Chemical), cocaine (Chemical), stroke (Disease), Stroke (Disease), cocaine (Chemical), Intracranial aneurysms (Disease), arteriovenous malformations (Disease), cerebral vasculitis (Disease), Cerebral infarction (Disease), intracerebral hemorrhage (Disease), subarachnoid hemorrhage (Disease), stroke (Disease), cocaine (Chemical), cocaine (Chemical), stroke (Disease), stroke (Disease), cocaine (Chemical), stroke (Disease), cocaine (Chemical), intracranial aneurysms (Disease), arteriovenous malformations (Disease), cocaine (Chemical), stroke (Disease), intracranial hemorrhage (Disease), cerebral infarction (Disease)


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

Input: Glyburide-induced hepatitis. Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.

Output: Chemical/Disease Entities: Glyburide (Chemical), hepatitis (Disease), hepatotoxicity (Disease), sulfonylureas (Chemical), glyburide (Chemical), sulfonylurea (Chemical), hepatotoxicity (Disease), type II diabetes mellitus (Disease), acute hepatitis-like syndrome (Disease), glyburide (Chemical), viral infection (Disease), drug-induced hepatitis (Disease), glyburide (Chemical), Glyburide (Chemical), acute hepatitis-like illness (Disease)


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

Input: Systolic pressure variation is greater during hemorrhage than during sodium nitroprusside-induced hypotension in ventilated dogs. The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.

Output: Chemical/Disease Entities: hemorrhage (Disease), sodium nitroprusside (Chemical), hypotension (Disease), hypotension (Disease), hemorrhage (Disease), HEM (Disease), sodium nitroprusside (Chemical), SNP (Chemical), HEM (Disease), hypotension (Disease), SNP (Chemical), hypotension (Disease), HEM (Disease), SNP (Chemical), HEM (Disease), SNP (Chemical), hypotension (Disease), hypotensive (Disease), hypovolemia (Disease), hypotension (Disease)


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

Input: Drug-induced arterial spasm relieved by lidocaine. Case report. Following major intracranial surgery in a 35-year-old man, sodium pentothal was intravenously infused to minimize cerebral ischaemia. Intense vasospasm with threatened gangrene arose in the arm used for the infusion. Since the cranial condition precluded use of more usual methods, lidocaine was given intra-arterially, with careful cardiovascular monitoring, to counteract the vasospasm. The treatment was rapidly successful.

Output: Chemical/Disease Entities: spasm (Disease), lidocaine (Chemical), sodium pentothal (Chemical), cerebral ischaemia (Disease), vasospasm (Disease), gangrene (Disease), lidocaine (Chemical), vasospasm (Disease)


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

Input: Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms. Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.

Output: Chemical/Disease Entities: isoflurane (Chemical), hypotension (Disease), cerebral aneurysms (Disease), oxygen (Chemical), isoflurane (Chemical), hypotension (Disease), cerebral aneurysm (Disease), subarachnoid haemorrhage (Disease), xenon (Chemical), isoflurane (Chemical), nitrous oxide (Chemical), oxygen (Chemical), hypotension (Disease), Hg (Chemical), isoflurane (Chemical), aneurysm (Disease), isoflurane (Chemical), hypotensive (Disease), hypotension (Disease)


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

Input: Allergic reaction to 5-fluorouracil infusion. An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.

Output: Chemical/Disease Entities: Allergic reaction (Disease), 5-fluorouracil (Chemical), allergic reaction (Disease), angioneurotic edema (Disease), 5-fluorouracil (Chemical), carcinoma of the oral cavity (Disease), cirrhosis (Disease), cisplatin (Chemical), impaired renal function (Disease), diphenhydramine (Chemical), prednisone (Chemical), allergic reaction (Disease)


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

Input: Amiodarone-induced sinoatrial block. We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia.

Output: Chemical/Disease Entities: Amiodarone (Chemical), sinoatrial block (Disease), sinoatrial block (Disease), amiodarone (Chemical), primary cardiomyopathy (Disease), Wolff-Parkinson-White syndrome (Disease), supraventricular tachycardia (Disease), amiodarone (Chemical), sinoatrial block (Disease), sinus bradycardia (Disease)


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

Input: Possible teratogenicity of sulphasalazine. Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.

Output: Chemical/Disease Entities: sulphasalazine (Chemical), inflammatory bowel disease (Disease), sulphasalazine (Chemical), congenital anomalies (Disease), ulcerative colitis (Disease), coarctation of the aorta (Disease), ventricular septal defect (Disease), Crohn's disease (Disease), Potter-type IIa polycystic kidney (Disease), rudimentary left uterine cornu (Disease), Potter's facies (Disease), hypoplastic lungs (Disease), absent kidneys and ureters (Disease), talipes equinovarus (Disease), sulphasalazine (Chemical)


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

Input: Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma. A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.

Output: Chemical/Disease Entities: Veno-occlusive liver disease (Disease), dacarbazine (Chemical), DTIC (Chemical), melanoma (Disease), veno-occlusive disease of the liver (Disease), dacarbazine (Chemical), DTIC (Chemical), melanoma (Disease), death (Disease), venous congestion (Disease), thrombosis (Disease)


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

Input: A case of tardive dyskinesia caused by metoclopramide. Abnormal involuntary movements appeared in the mouth, tongue, neck and abdomen of a 64-year-old male patient after he took metoclopramide for gastrointestinal disorder in a regimen of 30 mg per day for a total of about 260 days. The symptoms exacerbated to a maximum in a month. When the metoclopramide administration was discontinued, the abnormal movements gradually improved to a considerable extent. Attention to the possible induction of specific tardive dyskinesia is called for in the use of this drug.

Output: Chemical/Disease Entities: tardive dyskinesia (Disease), metoclopramide (Chemical), Abnormal involuntary movements (Disease), metoclopramide (Chemical), gastrointestinal disorder (Disease), metoclopramide (Chemical), abnormal movements (Disease), tardive dyskinesia (Disease)


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

Input: Further observations on the electrophysiologic effects of oral amiodarone therapy. A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.

Output: Chemical/Disease Entities: amiodarone (Chemical), intra-Hisian block (Disease), amiodarone (Chemical), atrial tachycardia (Disease), intraventricular conduction abnormalities (Disease), atrial tachycardia (Disease), amiodarone (Chemical), atrial flutter (Disease), Amiodarone (Chemical)


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

Input: Busulfan-induced hemorrhagic cystitis. A case of a busulfan-induced hemorrhage cystitis is reported. Spontaneous resolution occurred following cessation of the drug. The similarity between the histologic appearances of busulfan cystitis and both radiation and cyclophosphamide-induced cystitis is discussed and the world literature reviewed. In view of the known tendency of busulfan to induce cellular atypia and carcinoma in other sites, periodic urinary cytology is suggested in patients on long-term therapy.

Output: Chemical/Disease Entities: Busulfan (Chemical), busulfan (Chemical), busulfan (Chemical), cystitis (Disease), cyclophosphamide (Chemical), cystitis (Disease), busulfan (Chemical), carcinoma (Disease)


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

Input: Rebound hypertensive after sodium nitroprusside prevented by saralasin in rats. The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.

Output: Chemical/Disease Entities: hypertensive (Disease), sodium nitroprusside (Chemical), saralasin (Chemical), angiotensin (Chemical), halothane (Chemical), sodium nitroprusside (Chemical), SNP (Chemical), hypotension (Disease), halothane (Chemical), SNP (Chemical), saralasin (Chemical), angiotensin II (Chemical), SNP (Chemical), SNP (Chemical), increase in blood pressure (Disease), saralasin (Chemical), SNP (Chemical), saralasin (Chemical), halothane (Chemical), SNP (Chemical), SNP (Chemical), saralasin (Chemical), angiotensin (Chemical), hypotensive (Disease), halothane (Chemical), SNP (Chemical)


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

Input: Toxic hepatitis induced by antithyroid drugs: four cases including one with cross-reactivity between carbimazole and benzylthiouracil. OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.

Output: Chemical/Disease Entities: Toxic hepatitis (Disease), carbimazole (Chemical), benzylthiouracil (Chemical), hepatic adverse effects (Disease), hyperthyroidism (Disease), toxic hepatitis (Disease), carbimazole (Chemical), N  omercazole (Chemical), cholestatic (Disease), hepatitis (Disease), carbimazole (Chemical), hepatitis (Disease), Benzylthiouracil (Chemical), Basd  ne (Chemical), carbimazole (Chemical), hepatitis (Disease), neutropenia (Disease), Toxic hepatitis (Disease), hepatotoxicity (Disease)


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

Input: Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine. A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.

Output: Chemical/Disease Entities: vitamin B12 (Chemical), folinic acid (Chemical), toxicity (Disease), zidovudine (Chemical), vitamin B12 (Chemical), folinic acid (Chemical), zidovudine (Chemical), ZDV (Chemical), bone marrow suppression (Disease), human immunodeficiency virus (HIV)-infected (Disease), ZDV (Chemical), folinic acid (Chemical), vitamin B12 (Chemical), death (Disease), vitamin B12 (Chemical), folate (Chemical), toxicity (Disease), vitamin B12 (Chemical), folate (Chemical), myelosuppression (Disease), Vitamin B12 (Chemical), folinic acid (Chemical), ZDV (Chemical), ZDV (Chemical), myelotoxicity (Disease)


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

Input: Acute confusion induced by a high-dose infusion of 5-fluorouracil and folinic acid. A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.

Output: Chemical/Disease Entities: confusion (Disease), 5-fluorouracil (Chemical), folinic acid (Chemical), cisplatinum (Chemical), etoposide (Chemical), 5-fluorouracil (Chemical), folinic acid (Chemical), gastric adenocarcinoma (Disease), confusion (Disease), disorientation (Disease), irritability (Disease), coma (Disease), 5-fluorouracil (Chemical), folinic acid (Chemical), 5-fluorouracil (Chemical), folinic acid (Chemical), folinic acid (Chemical), neurotoxicity (Disease), 5-fluorouracil (Chemical), 5-fluorouracil (Chemical), neurotoxicity (Disease), fluoroacetate (Chemical), fluorocitrate (Chemical), thiamine (Chemical), dihydrouracil (Chemical), 5-fluorouracil (Chemical), folinic acid (Chemical), cancers (Disease)