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)

To evaluate the safety, toxicity, and maximum tolerated dose (MTD) of IFN beta-1a (Rebif, Serono Laboratories, Inc.) in patients with malignant diseases unresponsive to standard therapies and to assess the pharmacodynamics and pharmacokinetics associated with IFN beta-1a administration, an open-label, single-center phase I study was designed. Thirty-four patients were enrolled and treated with IFN beta-1a. All had measurable solid neoplasms or evaluable hematological malignancies. All patients received a single i.v. bolus dose of IFN-beta-1a on day 1, followed 7 days later by daily s.c. injections for 28 consecutive days. Successive groups of three patients received increasingly higher doses (in geometric progression from 1.5 million international units (MIU)/m2 to 24 MIU/m2) until dose-limiting toxicities were noted. Pharmacokinetic and biological studies, including measurement of the activity of 2',5'-oligoadenylate synthetase (2',5'-OAS) in peripheral blood mononuclear cells and serum levels of soluble Tac (CD 25) and beta-2 microglobulin, were performed on patients who agreed to participate. i.v. and s.c. doses of IFN beta-1a up to 24 MIU/m2 were administered. The most frequent adverse events (AEs) were constitutional symptoms. Grade III AEs during i.v. dosing included fever, elevation of bilirubin, and infection unrelated to therapy. No grade IV events were seen. AEs noted during continuous s.c. therapy included fever, liver transaminase increase, albuminuria, fatigue, nausea, myalgia, and rigors. Dose-limiting toxicities were encountered during s.c. dosing at the 24-MIU/m2 and 18-MIU/m2 dose levels and included gastrointestinal toxicity, elevations of aspartate aminotransferase and alanine aminotransferase, and albuminuria. The s.c. MTD was determined to be 12 MIU/m2, although there was great variability in the individual patient's ability to tolerate IFN beta-1a. 2',5'-OAS activity, thought to be indicative of IFN activity, increased within hours after i.v. and s.c. dosing, with the level remaining persistently elevated during the s.c. daily injections. The highest peak level was attained in the 6-MIU/m2 group. There was no evidence that the increase in 2',5'-OAS activity decayed with repetitive dosing, nor was there evidence of accumulation in this pharmacodynamic marker. Serum beta-2-microglobulin levels showed a modest time- and dose-dependent increase after s.c. administration of IFN beta-1a, with the largest increase seen at the 24-MIU/m2 dose level. There were no clear dose-dependent responses noted in soluble Tac serum levels. IFN beta-1a was well-tolerated when administered by a single i.v. bolus injection at doses up to and including 24 MIU/m2. Daily s.c. injections for at least 28 days were well-tolerated at doses up to and including 12 MIU/m2, with some patients tolerating doses twice as high as this. The MTD for the i.v. route could not be clearly determined according to the guidelines of the protocol. However, i.v. bolus doses up to 24 MIU/m2 were relatively well-tolerated. For the s.c. route, the MTD was determined to be 12 MIU/m2, but there was great interpatient variability, with some patients able to tolerate higher doses.
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PMID:A phase I study of recombinant interferon-beta in patients with advanced malignant disease. 1063 30

HELLP syndrome is a serious, life-threatening form of pre-eclampsia with a typical laboratory triad. The incidence of the disease is reported as being 0.17-0.85% of all live births. There has been, to date, neither reliable early recognition nor effective prevention of HELLP syndrome. As a result of endothelial dysfunction, activation of intravascular coagulation occurs with fibrin deposition in the capillaries and consecutive microcirculation disorders. The disease manifests itself on average between 32-34 weeks' gestation. HELLP syndrome will occur postpartum in up to 30% of the cases. The clinical cardinal symptom of the disease is right upper quadrant pain or epigastric pain accompanied with nausea, vomiting and malaise. In 20% of the cases with HELLP syndrome there is no hypertension and 5-15% of the pregnant patients present a low level of proteinuria or none at all. The early recognition of hemolysis is most sensitively managed by the determination of the serum haptoglobin. The increase of the aspartate transaminase (AST) and the alanine transaminase (ALT) often precedes a decrease in platelets. The course of HELLP syndrome is incalculable. It is universally agreed that a pregnancy from 32-34 weeks should be immediately delivered. Before 32-34 weeks, expectant management is generally possible in a perinatal center. The frequency for a repeated hypertensive disease in pregnancy ranges from 27% to 48%.
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PMID:HELLP syndrome. 1103 96

Two cases, mother and her son, suffering from acute poisoning with Tricholoma equestre were described. They had eaten 100-300 grams of this wild mushroom during nine consecutive meals. About 48 hours after the last meal containing the mushroom they developed fatigue, muscle weakness and myalgia, loss of appetite, mild nausea, profuse sweating. Maximal serum creatine kinase activity was 18,150 U/L in the mother and 48,136 U/L in the son. Maximal serum levels of aspartate aminotransferase and alanine aminotransferase were 802 U/L and 446 U/L, respectively, in the mother and 2002 U/L and 454 U/L, respectively, in the son. All routine biochemical tests were within normal range. No other causes of rhabdomyolysis such as parasitic, viral, immune diseases, trauma or exposure to medications were found. All the above mentioned symptoms and biochemical abnormalities disappeared within 23 days of hospitalization. Our observation confirms the results of Bedry and co-workers that Tricholoma equestre contains a toxin, which can cause rhabdomyolysis.
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PMID:Acute poisoning with Tricholoma equestre. 1218 17

A 37-year-old woman presented with increasing abdominal pain and jaundice. Six weeks before admission, she developed persistent diarrhea and jaundice of the skin. She also bruised easily, and her gums bled. In the subsequent weeks, her appetite decreased, she was fatigued, and she had nausea, vomiting, and abdominal distension. She had a history of drinking 1 quart of vodka every day for 20 years, with brief periods of abstinence; she stopped consuming alcohol 11 days before admission because it no longer provided symptomatic relief. Her past medical history was also notable for depression, including a suicide attempt 4 years earlier. She did not smoke, use illicit drugs, or have unprotected sexual intercourse. She had received no blood transfusions and had not traveled recently. She took no medications, except for occasional ibuprofen. On physical examination, she was thin and deeply jaundiced, and she trembled and responded slowly to questions. She was afebrile but tachypneic, and she had orthostatic hypotension. Her HEENT examination was notable for scleral and sublingual icterus, as well as crusted blood on her gums and teeth. The jugular veins were flat. The cardiac examination revealed tachycardia (heart rate, 103 beats per minute) without murmurs, rubs, or gallops. The abdomen was nontender and protuberant, with hypoactive bowel sounds; the spleen was not palpable, and there was no fluid wave or caput medusae. The liver percussed to 18 cm, with a smooth edge extending 10 cm below the costal margin. She had cutaneous telangiectases on her chest and bilateral palmar erythema. There was no peripheral edema. The neurologic examination was notable for asterixis. Her stool was guaiac positive. Laboratory studies revealed the following values: hematocrit, 21.2%; white blood cells, 17,310/mm(3); ammonia, 42 micromol/L; serum creatinine, 3.9 mg/dL; serum urea nitrogen, 70 mg/dL; albumin, 2.1 g/dL; total bilirubin, 26.8 mg/dL; alanine aminotransferase, 14 U/L; aspartate aminotransferase, 77 U/L; alkaline phosphatase, 138 U/L; prothrombin time, 103 seconds (international normalized ratio, 10.6); and urinary sodium, <5 mg/dL. Urinalysis revealed an elevated specific gravity and numerous muddy granular casts. Hepatitis A, B, and C serologies were negative. On abdominal ultrasound examination, there was no ascites, and the liver was echogenic. The portal and hepatic veins were patent, and the hepatic arteries were normal. The spleen measured 14 cm. What is the diagnosis?
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PMID:Cases from the Osler Medical Service at Johns Hopkins University. 1258 38

Sea-urchin stings may produce injurious and venomous wounds. Although numerous writers refer to the danger of pedicellarial stings, there is little worth-while clinical data. We report a case of sea-urchin injury with severe local reaction and acute hepatitis. A 47-y-o Taiwanese woman accidentally stepped on a sea urchin while scuba diving on a beach in Palau Islands. The puncture wounds were numerous and she felt faintness, and immediate and intense pain. Initial management included partial spine removal, betadine immersion, intravenous fluid and analgesics. She developed fever, chills, nausea, and persistent serous discharge and tenderness from the sites of stings in the following days. She was admitted due to right foot cellulitis, sea-urchin injuries of both soles and suspected toxic hepatitis on the 7th day after envenomation. Serum alanine transaminase was 810 U/L and aspartate transaminase 320 U/L; she received i.v. antibiotics and wound debridement for removal of residual stings. She recovered gradually and was discharged 2 w later. Travel related marine animal injury has an increasing tendency throughout the world. This case had the unusual presentation of severe local reaction and hepatitis; immediate and more aggressive spine removal might have lessened the degree of injury.
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PMID:Sea-urchin envenomation. 1464 Apr 80

The risk of transmission of hepatitis C virus (HCV) infection is an important problem for the health care worker. HCV transmission by blood splashing into eyes is very rare. In a hemodialyses department, a 23-year-old female nurse splashed blood from a patient who was anti-HCV positive into her eyes. She washed her eyes with water immediately and reported to the infection control department. She had never used intravenous drugs nor received transfusions. At the time of exposure, there was no abnormality in her laboratory tests. Her anti-HCV and HCV-RNA tests produced negative results. She was followed up for anti-HCV and alanine aminotransferase activity. After 6 months, she presented with sore throat, nausea, vomiting, fatigue, and weight loss. She had icterus and hepatomegalia. In laboratory tests, alanine aminotransferase level was 504 U/L, aspartate aminotransferase level was 388 U/L, and anti-HCV and HCV-RNA tests produced positive findings. She was treated with interferon alfa-2a for a 1-year period. After treatment, an HCV-RNA test produced negative results and transaminase levels were normal. In conclusion, splashing blood from patients who are HCV positive into the face or eyes is a risk for health care workers. They should be educated to prevent a nosocomial acquisition of bloodborne infection and they should observe protective precautions.
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PMID:Transmission of hepatitis C by blood splash into conjunctiva in a nurse. 1545 4

To determine the incidence, clinical and laboratory characteristics, and utility of molecular diagnosis of human monocytotropic ehrlichiosis (HME) in the primary care setting, we conducted a prospective study in an outpatient primary care clinic in Cape Girardeau, Missouri. One hundred and two patients with a history of fever for 3 days (>37.7 degrees C), tick bite or exposure, and no other infectious disease diagnosis were enrolled between March 1997 and December 1999. HME was diagnosed in 29 patients by indirect immunofluorescent antibody assay and polymerase chain reaction (PCR). Clinical and laboratory manifestations included fever (100%), headache (72%), myalgia or arthralgia (69%), chills (45%), weakness (38%), nausea (38%), leukopenia (60%), thrombocytopenia (56%), and elevated aspartate aminotransferase level (52%). Hospitalization occurred in 41% of case-patients. PCR sensitivity was 56%; specificity, 100%. HME is a prevalent, potentially severe disease in southeastern Missouri that often requires hospitalization. Because clinical presentation of HME is nonspecific, PCR is useful in the diagnosis of acute HME.
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PMID:Human monocytotropic ehrlichiosis, Missouri. 1472 Mar 99

The high-density lipoprotein (HDL)-Atherosclerosis Treatment Study showed that simvastatin plus niacin (mean daily dose 13 mg and 2.4 g, respectively) halt angiographic atherosclerosis progression and reduce major clinical events by 60% in patients with coronary artery disease (CAD) who have low HDL, in comparison with placebos, over 3 years. How safe and well-tolerated is this combination? One hundred sixty patients with CAD, including 25 with diabetes mellitus, with mean low-density lipoprotein cholesterol of 128 mg/dl, HDL cholesterol of < or =35 mg/dl (mean 31), and mean triglycerides of 217 mg/dl were randomized to 4 factorial combinations of antioxidant vitamins or their placebos and simvastatin plus niacin or their placebos. Patients were examined monthly or bimonthly for 38 months; side effects (gastrointestinal upset, nausea, anorexia, vision, skin, and energy problems, or muscle aches) were directly queried and recorded. Aspartate aminotransferase, creatine phosphokinase (CPK), uric acid, homocysteine, and fasting glucose levels were regularly monitored. A safety monitor reviewed all side effects and adjusted drug dosages accordingly. Patients who received simvastatin plus niacin and those on placebo had similar frequencies of clinical or laboratory side effects: any degree of flushing (30% vs 23%, p = NS), symptoms of fatigue, nausea, and/or muscle aches (9% vs 5%, p = NS), aspartate aminotransferase (SGOT) > or =3 times upper limit of normal (3% vs 1%, p = NS), CPK > or =2 times upper limit of normal (3% vs 4%, p = NS), CPK > or =5 times upper limit of normal, new onset of uric acid > or =7.5 mg/dl (18% vs 15%, p = NS), and homocysteine > or =15 micromol/L (9% vs 4%, p = NS). Glycemic control among diabetics declined mildly in the simvastatin-niacin group but returned to pretreatment levels at 8 months and remained stable for rest of the study. This combination regimen was repeatedly described by 91% of treated patients and 86% of placebo subjects as "very easy" or "fairly easy" to take. Thus, the simvastatin plus niacin regimen is effective, safe, and well tolerated in patients with or without diabetes mellitus.
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PMID:Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (The HDL Atherosclerosis Treatment Study). 1475 79

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

The explosive RDX (hexogen, cyclonite) is usually used for the production of C-4 explosive. The rare occurrence of accidental and intentional RDX intoxications has been reported during manufacturing process or in wartime. In this article, the authors report 5 cases of accidental oral RDX poisoning. On admission, observed signs and symptoms included repetitive generalized tonic-clonic convulsions, postictal coma, lethargy, confusion, hyperreflexia, postictal amnesia, nausea, vomiting, abdominal tenderness, sinusal tachycardia, dysrhythmia with frequent ventricular premature beats, generalized muscle spasms, and myoclonus. Leukocytosis, mild anemia, methemoglobinemia, elevated levels of blood glucose, serum aspartate transaminase, alanine transaminase, lactic dehydrogenase, creatine phosphokinase, amilase, hypokalemia, metabolic acidosis, proteinuria, glucosuria, and myoglobinuria were also noted. Plasma RDX concentrations were 268 to 969 ng/mL at 3 hours of ingestion. For management, supportive and symptomatic measures were taken. Whole-bowel irrigation might have been an effective therapeutic procedure due to probable slow gastrointestinal absorption of RDX. Three patients who developed severe metabolic acidosis underwent urgent hemodialysis. All patients were discharged 7 to 21 days after admission without any sequelae. Plasma RDX levels were strongly correlated with the clinical and laboratory manifestations. The available toxicological data on this rare accidental poisoning are reviewed in light of the literature.
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PMID:Accidental oral poisoning caused by RDX (cyclonite): a report of 5 cases. 1518 66


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