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

The diagnosis of obstetric cholestasis (OC) has serious implications for maternal, and especially fetal, health. Total serum bile acid concentration is an important investigation in any woman with itching in the absence of a rash during pregnancy. Results should be available within 1-2 working days. Pruritus plus raised total bile acids in the third trimester suggests a diagnosis of OC. Other biochemical abnormalities, usually a raised alanine aminotransferase, accompany or follow the finding of raised bile acids. Bile acids are sensitive, but not specific, markers for OC. The diagnosis is one of exclusion. The clinician should remain alert to other causes of liver dysfunction, either specific to pregnancy or not. Effective treatment is available that improves maternal biochemical indices and well-being. It is not clear whether such treatment reduces the risks to the fetus. More active management of OC pregnancies has reduced the associated fetal and perinatal mortality.
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PMID:Role of bile acid measurement in pregnancy. 1192 58

A multicenter, open labeled, randomized early Phase II study for CGS 20267 was conducted at the doses 0.5 mg once daily and 1.0 mg once daily in postmenopausal women with advanced breast cancer. Sixty-four patients were randomly assigned to the doses of either 0.5 mg once daily (n = 33) or 1.0 mg once daily (n = 31). Thirty-one patients were eligible for 0.5 mg group, and 29 for 1.0 mg group. A total of 57 patients (30 in the 0.5 mg group and 27 in the 1.0 mg group) were eligible for the evaluation of efficacy. There were 3 CR, 5 PR, 5 stable disease (SD: NC lasting over 24 weeks), 7 NC and 10 PD in the 0.5 mg group. The objective response rate (ORR) was 26.7%. There were 4 CR, 7 PR, 8 SD, 3 NC and 5 PD in the 1.0 mg group. The ORR was 40.7%. A total of 57 patients (29 in the 0.5 mg group and 28 in the 1.0 mg group) were eligible for safety evaluation. Adverse clinical events related to CGS 20267 in the 0.5 mg group were headache, nausea, cold sweat, sleepiness and muscle ache in the lower extremities (2 patients, incidence rate 6.9%) whereas those in the 1.0 mg group were generalized itching and generalized hot feeling (2 patients, incidence rate 7.1%). All of the adverse events were grade 1 except the generalized itching which was grade 2. CGS 20267-related abnormalities in the laboratory tests for the 0.5 mg group were a decrease in WBC, and increases in GOT, GPT, LDH and gamma-GTP (5 patients, 14.3%) whereas those in the 1.0 mg group were increases in GPT, gamma-GTP, alkaline phosphatase, and total bilirubin (1 patient, 3.6%). The increases in GOT and GPT were grade 2, but others were grade 1. The data show both CGS 20267 0.5 mg once daily and 1.0 mg once daily to be effective and tolerable in the treatment of postmenopausal women with advanced breast cancer.
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PMID:[CGS 20267 (Letrozole), a new aromatase inhibitor: early phase II study for postmenopausal women with advanced breast cancer]. 1197 39

When rats given D-galactosamine are then treated with the glucogenic amino acid alanine, their alanine aminotransferase (ALT) activity, total bilirubin level, and survival rate improve compared with when other amino acids are used. Here, we report a preliminary study of the clinical and pharmacological effects of alanine given to three patients with primary biliary cirrhosis (PBC). The patients were jaundiced and were in the end-stage of the disease. The treatment they had been receiving was continued while they were given 18 g of alanine per day for a planned 8 weeks. For all three patients, test results for total bilirubin, alkaline phosphatase, and ALT decreased by 25% or more from the base line at some time during treatment. The arterial ketone-body ratio increased. Two of the patients reported that their itching and fatigue lessened. Except for one patient given a second course, who reported nausea, adverse effects were not found. In end-stage PBC, alanine administration decreased the total bilirubin level and improved symptoms, so this compound may decrease jaundice in this disease. A long-term study of a larger group of patients is needed.
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PMID:Effects of alanine in patients with advanced primary biliary cirrhosis: preliminary report. 1264 33

A 40-year-old woman with a history of fever and arthralgia since age 17 had received long-term prednisolone (PSL) therapy. She was diagnosed with Takayasu's arteritis in 1980 and given PSL. The symptoms were well controlled until she developed itching in 1998. Laboratory tests showed elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total cholesterol, and immunoglobulin M (IgM). She tested positive for anti-mitochondria antibody and for both IgG and IgM anti-pyruvate dehydrogenases. Liver biopsy findings were typical of primary biliary cirrhosis (PBC). Our patient's clinical course suggested that an adequate amount of PSL to control Takayasu's arteritis does not necessarily prevent the development of PBC.
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PMID:A patient with Takayasu's arteritis treated with corticosteroids who developed primary biliary cirrhosis. 1279 18

Drugs may cause several overlapping syndromes of cholestasis, the pathophysiological syndrome resulting from impaired bile flow. These reactions comprise approximately 17% of all hepatic adverse drug reactions (ADRs) and they may be severe. Causes of 'pure' (bland) cholestasis include oestrogens and anabolic steroids; rarer associations are with antimicrobials and NSAIDs. 'Cholestatic hepatitis' is a common drug reaction in which liver injury and inflammation cause significant elevation of serum alanine aminotransferase (ALT) as well as cholestasis. Chlorpromazine and ketoconazole are classic examples, but it is now exemplified by amoxycillin-clavulanate and other oxy-penicillins. Chronic cholestasis results from small bile duct injury leading to the vanishing bile duct syndrome (VBDS), a disorder mimicking primary biliary cirrhosis, or from injury to larger bile ducts causing secondary sclerosing cholangitis. Whilst there is increasing evidence of a genetic predisposition to cholestatic drug reactions, there are currently no pretreatment tests to predict drug safety. Prevention of severe reactions therefore relies on early detection of liver injury and prompt drug withdrawal. Symptomatic management includes relief of pruritus and correction of fat-soluble vitamin deficiency. In small cohort studies, ursodeoxycholic acid (UDCA) arrested progressive cholestasis in two-thirds of cases, but evidence for use of corticosteroids is anecdotal. This review considers diagnosis, pathogenesis, prevention and management of drug-induced cholestasis, with particular reference to frequently- and newly-described causes.
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PMID:Drug-induced cholestasis. 1290 7

Clinical variants of hepatitis A include the prolonged, relapsing and cholestatic forms. Here, the first childhood case of hepatitis A, with a combination of the relapsing and cholestatic forms is presented, a 14-year old boy. In the first phase of the illness, while the AST and ALT levels were declined, th total and direct bilirubin and GGT were increased. The patient was thought to have the cholestatic form of hepatitis A. Du to intense pruritus and high bilirubin levels, ursodeoxycholic acid (UDCA) therapy was started. On the 17th day, the decreased AST and ALT levels began to increase, reaching levels as high as 484 U/L and 862 U/L, respectively. The UDCA treatment was stopped on the 64th day. On the 164th day, all his laboratory parameters were within normal limits, but the anti-HAV IgM was still positive.
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PMID:An unusual combination of relapsing and cholestatic hepatitis A in childhood. 1458 17

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) are associated with elevated transaminase levels in 1-3% of patients. Therapy with these drugs requires monitoring of alanine aminotransferase (ALT) levels because animal studies and premarketing clinical trials showed signs of hepatotoxicity that were primarily minor elevations of ALT. Nevertheless, postmarketing experience suggests that hepatotoxicity is rare, and that elevated ALT levels are reversible with continued therapy and probably are related to cholesterol lowering. Based on the low occurrence of ALT elevations and the lack of clinical evidence of hepatotoxicity, some clinicians are calling for a change in the current practice of monitoring liver function tests. We report, however, the case of a 71-year-old woman who was receiving atorvastatin and experienced elevated transaminase levels on two occasions, and developed pruritus on rechallenge with the drug. Thus, clinicians should be aware of asymptomatic elevations in liver function tests in patients receiving atorvastatin who do not have known risk factors for liver damage.
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PMID:Liver function test abnormalities and pruritus in a patient treated with atorvastatin: case report and review of the literature. 1474 Jul 94

The prolonged use of CNI has been associated with nephrotoxicity. MMF is a new immunosuppressive agent. In the present study, the consequences of introducing MMF and reduction of CNI in liver-transplant children were analysed. The present study included eight pediatric liver-transplant patients who had transplantation at least 5 yr previously, had stable graft function and had renal dysfunction as a probable side-effect of CNI therapy. CNI was replaced with MMF in all patients and serum creatinine, uric acid concentration, azotemia and creatinine clearance before and 6 months after study entry were measured. The patients were monitored closely for side-effects of MMF as well as graft function. Six months after study entry serum creatinine, uric acid concentration, azotemia and creatinine clearance improved in all the patients at the last follow-up. The aspartate aminotransferase and alanine aminotransferase concentrations were stable during the study period and did not observe any serum bilirubin increased as well. No side-effects were reported in patients on MMF. Only one patient reported temporary pruritus and nausea. The results indicate that renal dysfunction significantly improved when MMF therapy is started and CNI reduced. Furthermore present data suggest that the risk of acute allograft rejection is very low when the CNI desired reduction is achieved in not too short time and absolutely when the MPA levels are strictly monitored.
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PMID:Mycophenolate mofetil in pediatric liver transplant patients with renal dysfunction: preliminary data. 1487 Aug 93

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.
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PMID:Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum. 1556 72

Pancreatitis is a rare adverse effect of codeine. We report the case of a 42-year-old man who suffered from epigastric pain 1 hour after taking a tablet containing amoxicillin plus clavulanic acid (500/125 mg) and another tablet containing acetaminophen plus codeine (500/30 mg) for a respiratory infection. He was admitted to the emergency room and was treated with metamizol and pantoprazole. A few minutes after receiving intravenous doses of both drugs he developed a maculopapular and itching eruption with facial angioedema. Laboratory tests showed high levels of serum amylase, GOT, GPT and total bilirubin. Serological tests for several viruses showed no evidence of recent infection. Ultrasonography was negative for biliary lithiasis and showed only cholecystectomy performed in 2000. The patient was sent to our department where skin prick and oral challenge tests were performed with negative results. For ethical reasons, oral challenge with codeine was not carried out. We believe that our patient had codeine-induced pancreatitis. The most likely underlying pathophysiological mechanism was probably codeine-induced spasm of the sphincter of Oddi combined with sphincter of Oddi dysfunction related to a previous cholecystectomy. Allergy departments should be aware of possible non-immunological adverse.
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PMID:Pancreatitis due to codeine. 1594 33


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