Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ceforanide, a new cephalosporin antibiotic with a long half-life (3 h), can be administered twice daily. We evaluated its antimicrobial activity, pharmacology, and clinical efficacy. Twenty-seven patients with infections due to susceptible organisms received ceforanide, 0.5, 1, or 2 g, intramuscularly or intravenously every 12 h for 6 to 28 days. In vitro studies with the clinical isolates from 27 patients treated plus 263 additional isolates showed that ceforanide was active against cephalothin-susceptible gram-positive and gram-negative microorganisms. In addition, ceforanide inhibited 65% of cephalothin-resistant Escherichia coli and 65% of Enterobacter spp. at </=12.5 mug/ml. After a single 1-g intramuscular dose, the mean peak plasma concentration at 1 h was 48.9 mug/ml and that at 12 h was 4.7 mug/ml. Plasma accumulation occurred in some patients. The infections included 10 pneumonias, 3 with bacteremia and 1 with empyema; 11 soft tissue infections, 4 with abscesses and 3 with sepsis; and 3 urinary tract infections. One case each of endocarditis, osteomyelitis, and septic thrombophlebitis, all due to Staphylococcus aureus, were treated. Clinical response was satisfactory in all patients; bacteriological response was satisfactory in 26 of 27 patients. Ceforanide was well tolerated. Three patients developed mild increases in liver enzymes, and one developed slight eosinophilia. In another case, the antibiotic was discontinued because of a fivefold rise in serum glutamic-oxalacetic transaminase (aspartate aminotransferase) and serum glutamic-pyruvic transaminase (alanine aminotransferase) and a twofold rise in lactic acid dehydrogenase and alkaline phosphatase.
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PMID:Ceforanide: in vitro and clinical evaluation. 50 95

Fifteen women with pseudo-LE syndrome were studied. The dissease is characterized by recurrent attacks of fever, myalgia, arthralgia, visceral manifestations (pericarditis, myocarditis, pleurisy, pleural effusion and lung involvement). A prominent feature was an abnormal liver function with elevated GOT and GPT levels in serum, and impaired bromsuophalein elimination. The incidence of varicosities and thrombophlebitis was markedly increased. There was a correlation between complement-fixing antimitochondrial antibody (AMA) titres and the degree of activity of the disease. A reverse correlation was observed between antimitochondrial antibody titres and the absolute lymphocyte count in peripheral blood. In all instances the antimitochondrial antibodies were of polyclonal origin, belonging mainly to immunoglobulin class IgG and, in a few patients, IgM, IgA, or IgD. AMA titres, lymphocyte counts in peripheral blood, sedimentation rate, serum iron level and alpha1- and alpha2-globulins proved to be valuable in following the course of the disease. Other values (C-reactive protein, alpha1-acid glycoprotein, immunoglobulin and beta1c-globulin in serum) were not helpful.
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PMID:[Clinical and serological aspects of the pseudo-LE syndrome (author's transl)]. 112 30

An elevation of serum aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) may be produced in patients treated with i.v. full-dose HEPARIN. We studied the influence of low-dose s.c. HEPARIN (5,000 IU X 2) in 34 patients with acute myocardial infarction (AMI) and in 7 with cerebrovascular accidents or calf thrombophlebitis. Twelve patients (all males) with AMI showed a secondary elevation of GOT and GPT at about the sixth or seventh day after the commencement of therapy that persisted throughout the period of treatment. Four patients (two males and two females) with cerebrovascular accidents or thrombophlebitis showed similar increases of GOT and GPT.
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PMID:Hypertransaminasemia with subcutaneous heparin therapy. 732 13

The multiple dose tolerability and pharmacokinetics of tirilazad mesylate, a 21-aminosteroid free radical scavenger, were assessed in 50 healthy male volunteers. Volunteers were randomized to receive intravenous normal saline placebo (n = 10), citrate vehicle placebo (n = 10), or 0.5 mg/kg/day (n = 6), 1.0 mg/kg/day (n = 6), 2.0 mg/kg/day (n = 6), 4.0 mg/kg/day (n = 6), or 6.0 mg/kg/day (n = 6) tirilazad mesylate in divided doses every 6 hours for 5 days, for a total of 21 doses. Drug was infused over 10 or 30 minutes. All tirilazad mesylate treatment groups and the citrate vehicle group had significantly more frequent and more intense pain at the injection site than did the saline group, but the pain intensity did not require interruption of dosing. Three episodes of clinical thrombophlebitis were observed. No statistically significant effects of tirilazad mesylate on blood pressure, heart rate, electrocardiograms, or renal function were apparent. Moderate and transient increases in serum alanine transaminase were observed in several subjects. In the 6.0 mg/kg/day group, 50% of the subjects exhibited increased alanine transaminase. Tirilazad mesylate did not significantly affect measures of glucocorticoid activity (blood glucose, adrenocorticotropic hormone, cortisol, eosinophil, or lymphocyte levels). Tirilazad mesylate pharmacokinetics were linear over the dosage range studied. Steady state appeared to be achieved by the fifth day of dosing. After the last dose, a mean terminal half-life of 35 hours was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of the pharmacokinetics and tolerability of tirilazad mesylate, a 21-aminosteroid free radical scavenger: II. Multiple-dose administration. 844 Jul 68

The safety and tolerability of quinupristin/dalfopristin were assessed in both comparative and non-comparative trials (2298 quinupristin/dalfopristin-treated patients). In comparative clinical trials, the most frequent systemic adverse events related to quinupristin/dalfopristin were nausea (4.6%), diarrhoea (2.7%), vomiting (2.7%) and skin rash (2.5%). The comparator group showed similar rates, except that nausea was significantly more common (7.2%; P = 0.01). In non-comparative trials, arthralgia and myalgia were reported most frequently but were reversible upon treatment discontinuation. The renal, inner ear, cardiovascular and central nervous systems were not implicated as significant target organs for toxicity. The most frequent local adverse events related to infusion of quinupristin/dalfopristin were inflammation, pain, oedema, infusion site reaction and thrombophlebitis. Results of laboratory tests while on therapy were comparable for quinupristin/dalfopristin and comparator groups, except that increases in conjugated bilirubin of >5 x the upper limit of normal were reported in 5.5% of quinupristin/dalfopristin recipients; increases in total bilirubin of >5 x the upper limit of normal occurred in 1.5%. Comparator recipients more frequently had increases in alanine aminotransferase and alkaline phosphatase. Quinupristin/dalfopristin inhibits the cytochrome P450 3A4-mediated metabolism of drugs including midazolam, nifedipine, terfenadine and cyclosporin. Therefore, plasma drug monitoring and/or dosage reduction of these agents is prudent. Concomitant administration of drugs that can prolong the electrocardiographic QTc interval should be avoided. Quinupristin/dalfopristin is visually and chemically compatible with commonly used drugs of various classes, but it is not compatible with sodium chloride solution and certain other drugs, including some antimicrobials. Therefore, when prescribing quinupristin/dalfopristin, clinicians should be aware of the potential for peripheral venous intolerance, arthralgias and myalgias, increases in conjugated bilirubin, interactions with drugs metabolized by the cytochrome P450 3A4 isoenzyme and certain physico-chemical incompatibilities. However, multiple studies have shown that the safety and tolerability of quinupristin/dalfopristin are generally favourable, and that it provides clear benefits to ill patients with severe gram-positive infections.
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PMID:Safety and tolerability of quinupristin/dalfopristin: administration guidelines. 1051 96

Lemierre's syndrome is a rare but a life threatening condition which affects young healthy individuals, was first described by Dr.Andre Lemierre in 1936. Incidence rates are between 0.6 and 2.3 per million population. It is found more commonly in males, with a male to female ratio of approximately 2:1. Its pathogenesis consists of the development of infectious thrombophlebitis in the internal jugular vein or one of its branches caused by a focal sepsis, mostly localized in the oropharynx, leading to generalized multiorgan metastatic infections, generally to the lung. This computerized tomography (CT) neck with intravenous contrast is from a 24 year old female who presented with a two day history of fever, hypotension and respiratory failure. The physical exam was positive for diminished breath sounds bilaterally on lung exam. Complete blood count revealed a leukocytosis of 16,200 u/L with 70% neutrophils and 9% bands, hemoglobin of 13.4mg/dl and severe thrombocytopenia with a platelet count of 34,000 u/L; comprehensive metabolic panel revealed sodium 140mmol/L, potassium 2.9mmol/L, bicarbonate 26mmol/L, blood urea nitrogen (BUN) 16mg/dl, creatinine 0.8mg/dl, calcium 7.2 mg/dl, albumin 2.4g/dl, total bilurubin 3.1mg/dl, AST 81 U/L, ALK 101 U/L, ALT 35U/L. CT chest revealed multiple cavitary opacities in both lungs. Blood cultures were positive for Fusobacterium necrophorum. CT scan neck showed a filling defect of the right internal jugular vein consistent with a thrombus and multiple enlarged cervical lymph nodes. Treatment is medical with intravenous antibiotics and anticoagulation. References: 1. Carlson ER, Bergamo DF, Coccia CT. Lemierre's syndrome: two cases of a forgotten disease. J Oral Maxillofac Surg 1994; 52:74-78. 2. Moore-Gillon J, Lee TH, Eykyn SJ, Phillips I. Necrobacillosis: a forgotten disease. BMJ 1984;288:1526-1527. 3. Jones C, Siva TM, Seymour FK, O'Reilly BJ. Lemierre's syndrome presenting with peritonsillar abscess and VIth cranial nerve palsy. J Laryngol Otol 2006;120:502-504 4. Mohammed Iqbal Syed et al. Lemierre Syndrome: Two Cases and a Review. Laryngoscope, 117:1605-1610, 2007 5. Vohra A, Saiz E, Ratzan KR. A young woman with a sore throat, septicaemia, and respiratory failure. Lancet 1997; 350:928.
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PMID:"A forgotten disease": a case of Lemierre syndrome. 1946 52