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

Imipenem-cilastatin was evaluated for tolerability and efficacy in a multicenter open, noncomparative trial involving 178 infants and children with bacterial infections. Imipenemcilastatin was administered in total daily dosages of 100 mg/kg for patients up to 3 years of age and 60 mg/kg for those more than 3 years of age. Favorable clinical response was achieved in 98 of 100 patients judged evaluable for efficacy. Adverse effects were generally mild and reversible and included diarrhea alone or with vomiting (5.1%), irritation of intravenous infusion site (3.3%) and rash (2.2%). Changes in laboratory test values reported most frequently were thrombocytosis (8.9%), elevations in aspartate aminotransferase (7.9%) and alanine aminotransferase (5.6%) and eosinophilia (8.4%). This safety profile appears to be comparable to that of other beta-lactam antibiotics. Moreover imipenem-cilastatin was effective in infections caused by a broad spectrum of pathogens that include Haemophilus influenzae, Staphylococcus aureus, P. aeruginosa and anaerobes. These attributes suggest that imipenem-cilastatin should be safe and effective in selected pediatric patients.
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PMID:Imipenem-cilastatin in pediatric patients: an overview of safety and efficacy in studies conducted in the United States. 268 88

The clinical safety of aztreonam in the treatment of suspected aerobic gram-negative infections was assessed in 346 patients who received single doses and in 2,388 patients who received multiple doses. Of those administered multiple doses, 163 (6.8%) experienced 172 adverse clinical effects. The most common were local reactions at the injection site, rash, diarrhea, and nausea and/or vomiting. Among aztreonam and control groups, three-fold increases in serum aspartate aminotransferase (SGOT) and serum alanine aminotransferase (SGPT) values occurred at comparably low frequencies; the mean values of SGOT and SGPT were slightly higher in patients administered aztreonam than in those given cefamandole. Treatment with aztreonam was discontinued in 51 (2.1%) of 2,388 patients because of adverse clinical effects or abnormal laboratory test values. Suprainfections (infections due to new pathogens occurring at the original site of infection during treatment with the study drug that were treated with another antibiotic) were reported in 2%-6% of aztreonam-treated patients, a frequency similar to that observed in control groups. Aztreonam is well tolerated and has a safety profile similar to that of other beta-lactam antibiotics.
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PMID:Safety profile of aztreonam in clinical trials. 293 85

Aztreonam was used successfully in 17 of 17 patients with orthopedic infections due to gram-negative bacilli (11, osteomyelitis; six, septic arthritis). Duration of treatment ranged from 14 to 55 days, and the period of follow-up was four to 18 months. Causative organisms included Pseudomonas aeruginosa, Serratia marcescens, Enterobacter gergoviae, Citrobacter diversus, Proteus mirabilis, and Enterobacter aerogenes. Aztreonam was well tolerated. The only definite reactions attributable to aztreonam were asymptomatic increases in serum aspartate aminotransferase (SGOT) and serum alanine aminotransferase (SGPT) in four patients; none of these reactions interfered with completion of therapy. Adverse reactions that were possibly attributable to aztreonam included rash (two patients), diarrhea (one patient), and leukopenia (one patient). All of these patients were receiving antibiotics active against gram-positive organisms in mixed infections in addition to aztreonam. Aztreonam is a promising new monobactam without significant toxicity. It has good activity against gram-negative aerobic bacteria, including P. aeruginosa, and is effective in the treatment of serious infections due to gram-negative aerobes.
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PMID:Aztreonam in the treatment of bone and joint infections caused by gram-negative bacilli. 293 86

A patient who developed chronic salicylism associated with salicylate therapy for treatment of juvenile rheumatoid arthritis is described, and the clinical presentation and treatment of chronic salicylism are reviewed. A 5 1/2-year-old boy was receiving aspirin 150/mg/kg/day for treatment of juvenile rheumatoid arthritis. While on salicylate therapy, the patient developed tachypnea and became increasingly hyperthermic, lethargic, and disoriented. The patient developed a maculopapular rash, weakness, and a decreased level of consciousness during the 11 days before admission to the hospital. Physical examination and laboratory determinations revealed that the patient had hypoprothrombinemia, hypoglycemia, and severe hepatic encephalopathy secondary to long-term salicylate toxicity. The patient was treated for hypoglycemia, electrolyte imbalances, thrombocytopenia, and anemia and was discharged after 24 days. Diagnosing chronic salicylism with hepatic dysfunction was difficult because the symptoms are similar to those of stage I to stage II Reye's syndrome. Liver enzymes, including aspartate aminotransferase (also called SGOT), alanine aminotransferase (also called SGPT), alkaline phosphatase, and lactate dehydrogenase, may be elevated in juvenile arthritis patients with hepatic dysfunction. Liver dysfunction usually improves when salicylate therapy is discontinued. Supportive therapy should always be used in symptomatic patients. Children on long-term, high-dose salicylate therapy should be monitored closely, and baseline liver function tests should be performed. The clinical effectiveness of administering sodium bicarbonate in attempts to alkalinize urine and increase salicylate elimination is controversial. In patients with juvenile rheumatoid arthritis who develop chronic salicylism, careful analysis of the patient's medication history, laboratory values, and clinical presentation are necessary to rule out Reye's syndrome.
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PMID:Chronic salicylism in a patient with juvenile rheumatoid arthritis. 370 82

Triethylene tetramine dihydrochloride (trien) is a copper chelating agent used as the alternative drug of choice in the treatment of Wilson's disease. Because of its apparent safety, we have used the drug in 4 patients with primary biliary cirrhosis in whom penicillamine had to be withdrawn because of serious side effects. Trien is an effective cupruretic drug in primary biliary cirrhosis, but its use is limited by the occurrence of side effects that occurred in all 4 patients. Three patients developed gastrointestinal side effects, and one of these patients developed a skin rash. The 4th patient developed acute rhabdomyolysis within 48 hr of receiving the first dose of the drug. One patient tolerated therapy for 20 wk, and, although her liver copper concentration did not show a marked fall, aspartate transaminase levels fell, and her IgM concentration fell to normal. Trien is an unsuitable copper chelating drug in primary biliary cirrhosis, although it remains the alternative drug of choice in Wilson's disease.
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PMID:Triethylene tetramine dihydrochloride toxicity in primary biliary cirrhosis. 644 5

Lyme disease, caused by a tick-transmitted spirochete, typically begins with a unique skin lesion, erythema chronicum migrans. Of 314 patients with this skin lesion, almost half developed multiple annular secondary lesions; some patients had evanescent red blotches or circles, malar or urticarial rash, conjunctivitis, periorbital edema, or diffuse erythema. Skin manifestations were often accompanied by malaise and fatigue, headache, fever and chills, generalized achiness, and regional lymphadenopathy. In addition, patients sometimes had evidence of meningeal irritation, mild encephalopathy, migratory musculoskeletal pain, hepatitis, generalized lymphadenopathy and splenomegaly, sore throat, nonproductive cough, or testicular swelling. These signs and symptoms were typically intermittent and changing during a period of several weeks. The commonest nonspecific laboratory abnormalities were a high sedimentation rate, an elevated serum IgM level, or an increased aspartate transaminase level. Early Lyme disease can be diagnosed by its dermatologic manifestations, rapidly changing system involvement, and if necessary, by serologic testing.
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PMID:The early clinical manifestations of Lyme disease. 685 26

A study of the clinical profile of 59 patients who presented with hepatitis A virus infection showed that dark urine, fatigue, gastrointestinal complaints, and fever were the most common presenting symptoms. The most frequent physical findings were hepatomegaly and jaundice. The mean presenting laboratory tests included total bilirubin of 5 mg/dL, alkaline phosphatase of 269 units/L, and serum aspartate aminotransferase and alanine aminotransferase levels of 1442 mIU/mL and 1952 mIU/mL, respectively. Atypical manifestations included relapse, cholestasis, rash, and arthralgia. Two patients presented with hepatitis A and concomitant type I autoimmune chronic hepatitis, and both required immunosuppressive therapy. Five patients who presented with hepatitis A were pregnant, and during follow-up, none of their infants developed elevated serum transaminase values or had detectable IgM anti-HAV antibody. All 59 patients experienced complete clinical and biochemical recovery within 6 months after onset of illness.
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PMID:Clinical manifestations of hepatitis A: recent experience in a community teaching hospital. 787 41

A double-blind, randomized study was undertaken to evaluate the efficacy and safety of fluvastatin as monotherapy and as combination therapy with niacin in the treatment of hypercholesterolemia refractory to diet. Seventy-four patients with plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 160 mg/dL were treated with fluvastatin, 20 mg/d, or placebo for 6 weeks. Thereafter, immediate-release niacin, at a dosage titrated to a maximum of 3 g/d, was added to both regimens for another 9 weeks. All adverse events were monitored, with particular attention to the evaluation of liver and muscle enzymes. Initial analysis of the data shows that fluvastatin and its combination with niacin was well tolerated and was not associated with any serious adverse events. Small, transient, asymptomatic rises in aspartate aminotransferase (AST) occurred in 28.9% of fluvastatin-niacin treated patients compared to 8.3% in the niacin-placebo control arm (p < 0.05). These were considered clinically insignificant in that no transaminase elevations > 3 times the upper limit of normal occurred. No evidence of myopathy, creatine kinase levels exceeding 10 times the upper limit of normal, myositis, or rhabdomyolysis were demonstrated in this short-term trial. The majority of adverse events resulting in patient withdrawals were ascribed to niacin therapy and included cutaneous vasodilatation, flushing, itching, and rash. These preliminary results suggest that fluvastatin, both alone and combined with niacin, is an effective, safe, and well-tolerated treatment for hypercholesterolemia.
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PMID:Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. 819 20

6-Dimethylamino-9-(beta-D-arabinofuranosyl)-9H-purine (ara-DMAP) effectively prevented the development of rash and appreciably reduced viremia in simian varicella virus-infected monkeys. Doses of 100 and 50 mg/kg/day, administered orally, were highly effective. The lowest dose of 20 mg/kg/day was much less effective in preventing moderate viremia. However, the 20 mg/kg/day did prevent the development of rash in two of three monkeys. All three doses of ara-DMAP reduced liver infection as reflected by lower aspartate aminotransferase values in the sera of the African green monkeys. Orally administered ara-DMAP was rapidly absorbed. However, significant variation among individual monkeys in the AUC values, peak plasma levels, and plasma half-lives were observed.
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PMID:6-Dimethylamino-9-(beta-D-arabinofuranosyl)-9H-purine: pharmacokinetics and antiviral activity in simian varicella virus-infected monkeys. 845 45


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