Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven patients with beta thalassemia major were entered into the trial of the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Their ages ranged from 17 to 26 years (mean +/- SD, 22.3 +/- 2.7). Six were male and five were female. L1 was administered at an initial daily dose of 42.5 to 60 mg/kg as a single dose. After 4 weeks, the dose was increased to 85 to 119 (102 +/- 10.7) mg/kg for 191 to 352 days divided into either two or four doses daily, except for one patient who developed agranulocytosis after 11 weeks and was taken off the trial. Initial serum ferritin values in the remaining 10 patients ranged between 1,000 and 9,580 (5,549 +/- 3,333) micrograms/L and at end of the trial their mean serum ferritin was significantly lower (4,126 +/- 2,278; P less than .05 using the paired t-test). Urinary iron excretion at a daily dose of 85 to 119 mg/kg administered as two divided doses ranged between 0.14 and 0.82 (0.44 +/- 0.26) mg/kg/24 h. In three patients, the four doses per day schedule caused substantially more iron excretion than the same total dose divided into two. During the course of the trial, several possible adverse effects have been encountered. One patient (female, aged 20) developed agranulocytosis 11 weeks after starting treatment and 6 weeks after beginning treatment with a daily dose of 105 mg/kg. This patient's neutrophil count recovered spontaneously 7 weeks after the discontinuation of L1. A decrease in serum zinc levels to subnormal levels was observed in four patients with symptoms of dry skin, with an itchy scaly rash in two that was associated with low serum zinc levels that responded to zinc therapy. Urinary zinc levels ranged from 4.7 to 23.4 (13 +/- 5.5) mumol/24 h and were above 9 mumol/24 h (upper limit of normal) in eight patients. Mild nausea occurred in three patients and transient diarrhea in a fourth. Mild musculoskeletal symptoms occurred in three patients but settled without discontinuation of L1 therapy in two and with temporary discontinuation of L1 in the third. A transient increase in serum aspartate transaminase was also noted in five patients, but serum aspartate transaminase levels subsequently decreased in all of them. No cardiovascular, neurologic, renal, or retinal toxicities were demonstrable. These results confirm that L1 is an effective oral iron chelator. Further clinical trials are needed to determine the incidence and severity of adverse effects.
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PMID:Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in thalassemia major. 846 82

In patients with unexplained pain after cholecystectomy, morphine often induces pain and may increase plasma aspartate aminotransferase (AST) activity because of exaggerated or prolonged rises in pressure within the biliary system. These anomalous effects of morphine may be mediated by activation of autonomic or related afferent nuclei. In this study, 16 patients with pain and increases in AST after morphine were further studied after pre-treatment with dexamethasone and hydrocortisone. Pre-treatment with dexamethasone decreased scores for pain and nausea and prevented or attenuated increases in plasma AST and glucose; these effects were not observed after pre-treatment with hydrocortisone. Serial changes in plasma concentrations of catecholamines were determined in 8 patients and showed that pre-treatment with dexamethasone, but not hydrocortisone, was associated with lower concentrations of norepinephrine and epinephrine with overall reductions of 53% and 67%, respectively. These observations are consistent with a role for sympatho-adrenomedullary activation in abdominal pain induced by morphine. The different effects of dexamethasone and hydrocortisone raise the possibility that sympatho-adrenomedullary activation after morphine is influenced by the interaction of cortisol with type I glucocorticoid receptors which have a low affinity for dexamethasone and a high affinity for cortisol.
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PMID:Differential effect of glucocorticoids on abdominal pain induced by morphine. 174 37

The characteristics of liver damage associated with the use of diclofenac, a popular nonsteroidal anti-inflammatory drug, were investigated by reviewing adverse drug reaction reports for Australia. Twenty six patients were reported for whom diclofenac was the sole suspected drug cause of their liver damage. The average age of the patients was 64 years (range 37-84 years); 19 (70%) were women. The most common clinical features were jaundice, hepatomegaly, anorexia, and nausea. Features of drug hypersensitivity were not reported. Duration of treatment with diclofenac before the onset of the illness ranged from 6-417 days (median 76 days). The most prominent biochemical abnormalities were raised serum aspartate transaminase and alanine transaminase activity of up to 30 to 40 times the upper limit of the normal range. Recovery generally started soon after withdrawal of diclofenac and the decrease in aspartate transaminase and alanine transaminase for the group was exponential, with half lives of around 13 days. The average total dose taken by 18 patients for whom accurate data were available was 8.7 g (range 1.4-63.5 g) and, unexpectedly, there was a significant relation between the logarithm of the dose of diclofenac and the logarithms of the peak and mean transaminase levels. Hepatocellular damage during treatment with diclofenac seems to be a rare event. From this analysis of Australian reports it seems that in a small subgroup of patients liver injury may be a direct toxic effect of diclofenac or a metabolite.
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PMID:Diclofenac hepatitis. 175 73

The tolerability of omeprazole was compared to control agents in 68 clinical studies that enrolled a total of 4846 patients, of whom 3096 received omeprazole. The incidence of adverse experiences was independent of omeprazole dose administered, the age of the patients, and the disease treated (duodenal ulcer or endoscopically verified gastroesophageal reflux disease). The most common clinical adverse experiences were headache, diarrhea, abdominal pain, and nausea. The most common laboratory adverse experiences were elevated aspartate aminotransferase and elevated alanine aminotransferase. Omeprazole was well tolerated, and the incidence of clinical and laboratory adverse experiences was similar in patients receiving omeprazole, placebo, cimetidine, or ranitidine.
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PMID:Comparative tolerability profile of omeprazole in clinical trials. 191 59

A 49 year old female was started on disulfiram. Six weeks later she was given naproxen because of epicondylitis. After 5 days' treatment with naproxen she complained of nausea, anorexia and jaundice. At admission, bilirubin was 452 mumol/l, aspartate aminotransferase (ASAT) 1925 U/I, alanine aminotransferase (ALAT) 2815 U/I and prothrombin time measured as Normotest was 27%. The patient developed a fulminant hepatitis and died in hepatic coma almost four weeks after the introduction of naproxen. Postmortem examination disclosed a small liver (1,100 g) and histological examination showed massive necrosis and collapse of the lobules. The naproxen was the most probable cause of death, but it is impossible to exclude disulfiram as causative agent.
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PMID:[Fulminating hepatitis after treatment with naproxen and/or disulfiram?]. 200 Jun 13

We investigated whether clinical and laboratory variables can predict perfusion status after t-PA administration, by using the data from 138 patients who received t-PA during the Thrombolysis in Myocardial Infarction (TIMI) I study. All clinical and laboratory variables that were collected at baseline or during perfusion for TIMI I were evaluated by the current study. Via stepwise discriminant analysis, 7 variables were closely associated with perfusion status at 90 minutes (listed in the order of their discriminant effect): baseline grade of stenosis in the infarct-related coronary artery, whether nausea was present during the infusion, baseline aspartate aminotransferase (SGOT) concentration, whether arrhythmias were present during the infusion, baseline fibrinogen concentration, baseline partial thromboplastin time, and baseline diastolic blood pressure. Baseline severity of stenosis and the likelihood of there being reperfusion were inversely related. Eighty-four percent of patients with adequate perfusion after 90 minutes of t-PA infusion were classified correctly, but only 50% of those without perfusion at 90 minutes were classified correctly. In addition, since 70% of the TIMI I patients, on average, did achieve perfusion, the use of these 7 variables added little predictive information. Our findings suggest that 1) there is as yet no practical way to predict reperfusion after t-PA therapy and 2) the severity of coronary stenoses, if known ahead of time, should be considered when selecting patients for thrombolytic therapy.
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PMID:Prediction of coronary artery reperfusion after tissue plasminogen activator infusion. 211 85

In a randomised, double-blind study the efficacy and toxicity of oral fluconazole 50 mg daily and ketoconazole 200 mg daily were compared for the treatment of oropharyngeal candidiasis in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). 20 episodes (18 patients) were treated with fluconazole and 20 episodes (19 patients) with ketoconazole. Pretreatment clinical features and laboratory test results were similar in both groups. 17 episodes (85%) in the fluconazole group and 16 (80%) in the ketoconazole group could be evaluated. There was clinical cure at the end of therapy in all fluconazole-treated and 12 of 16 (75%) ketoconazole-treated episodes. Cultures were negative at the end of therapy in 87% of the fluconazole group and 69% of the ketoconazole group. 1 patients stopped taking fluconazole because of severe nausea. 1 of 18 fluconazole-treated and 4 of 19 ketoconazole-treated patients had transient rises in alanine or aspartate aminotransferase. Fluconazole seemed more effective than ketoconazole in the treatment of oral thrush among AIDS and ARC patients.
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PMID:Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. 256 63

Data from 1,878 courses of intravenous ciprofloxacin therapy, administered to 1,869 patients in 59 clinical trials, were analyzed for drug safety. The 985 men and 884 women had a mean age of 50 years, and more than one third were over 60 years of age. An overwhelming majority had at least one accompanying systemic illness, and the condition of more than half the patients was only fair or poor at the onset of therapy. Ciprofloxacin was administered in a unit dose of either 200 mg (68 percent of the patients) or 300 mg (28 percent) by intravenous infusion, generally over 30 minutes every 12 hours, at a mean daily dosage of 456 mg. The duration of intravenous therapy ranged from one to 57 days, with a mean of seven days; over 1,000 patients were treated for more than five days. Adverse events considered probably or possibly related to intravenous ciprofloxacin were reported in 15.8 percent of the courses; therapy was discontinued prematurely in 3 percent. Local reactions at the site of infusion were the most common, occurring in 4.4 percent of the courses. Changes in blood chemistry values (4.1 percent) included increases in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Reports of adverse effects referable to the gastrointestinal tract (3.0 percent) were primarily nausea and diarrhea. Central nervous system reactions (1.8 percent) included convulsive seizures, headache, and dizziness. In comparative trials, events considered probably or possibly drug related were reported for 17.3 and 13.6 percent of the ciprofloxacin- and ceftazidime-treated patients, respectively. The incidence of adverse events other than local reactions at the infusion site was not significantly different between the ciprofloxacin- and ceftazidime-treated patients (12.7 percent versus 11.0 percent, p greater than 0.2).
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PMID:Safety of intravenous ciprofloxacin. A review. 268 31

Sixty-six patients with recurrent respiratory papillomatosis of juvenile onset were treated for six months with interferon alfa-n1 (Wellferon) in a randomized crossover trial. Half received interferon alfa-n1 intramuscularly at a dosage of 5 megaunits per square meter daily for 28 days and then thrice weekly for five months, followed by six months of observation. The other half were observed for six months and then treated. Operations were performed every two months to assess disease extent by a scale developed for this purpose. The score for the patients during the first observation period was stable. There was a statistically significant lowering of score in patients receiving interferon alfa-n1 during both periods of drug administration. Eight of 57 patients with assessable airway disease achieved complete remission, as did one additional patient with disease limited to the nasopharynx. No patients achieved complete remission during six months of observation alone. This difference was statistically significant. Patients without tracheostomy were significantly more likely to achieve remission than those with a tracheostomy. The patients who were observed after discontinuation of the drug therapy showed a significant rise in score within four months. Symptoms of toxicity included transient fever, fatigue, nausea, and headache. Elevations in serum aspartate aminotransferase levels occurred in 64% of the patients. There was an inverse correlation between age and the ability to tolerate the medication. The dose studied may be close to the maximum tolerated dose. It appears that interferon alfa-n1 as an adjuvant to routine surgical management is effective in slowing the growth of respiratory papillomas.
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PMID:Randomized surgical adjuvant trial of interferon alfa-n1 in recurrent papillomatosis. 304 38

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of omeprazole are reviewed. Omeprazole, a substituted benzimidazole, has a unique site and mechanism of action because it inhibits the proton pump--i.e., hydrogen, potassium adenosine triphosphatase (H+,K+-ATPase)--and consequently blocks the final common step in the gastric acid secretory pathway. Omeprazole inhibits basal and histamine-, gastrin- and pentagastrin-stimulated gastric hydrochloric acid secretion. It produces a dose-dependent reduction in gastric acidity, gastric acid output, and gastric juice volume and has variable effects on pepsin secretion. Omeprazole has no documented effect on esophageal motility or lower esophageal sphincter pressure. Omeprazole is variably absorbed from the gastrointestinal tract, and food appears to decrease the rate, but not the extent, of drug absorption. The drug is approximately 95% bound to plasma proteins and is metabolized to inactive components that are enterohepatically or renally eliminated. Omeprazole is more effective (in most studies) than H2-receptor antagonists in treating duodenal ulcer, at least as effective in treating benign gastric ulcer, and more effective in treating reflux esophagitis. Omeprazole has been used successfully in patients with Zollinger-Ellison syndrome refractory to treatment with H2-receptor antagonists. Gastrointestinal complaints (nausea and diarrhea) are the most commonly reported adverse effects associated with omeprazole therapy. The most frequently reported laboratory abnormality occurring with omeprazole use is elevation of serum aspartate aminotransferase and alanine aminotransferase concentrations. Omeprazole will serve a valuable role in the management of gastrointestinal tract ulcers and hypersecretory conditions.
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PMID:Therapeutic evaluation of omeprazole. 306 85


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