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)

In order to determine the usual dose in the first line therapy and a high dose in the second or third line therapy, a dose finding study of a novel antiestrogen NK 622 (toremifene citrate) was performed in patients (pts) with advanced or recurrent breast cancer. NK 622 was orally administered daily once for more than 8 weeks. In pts without previous drug therapy or in pts with cancer relapse after adjuvant therapy, the response rates [(CR + PR)/total] were 24.1% (7/29), 13.8% (4/29), 20.0% (1/5) and 40.0% (2/5) at doses of 40, 60, 120 and 240 mg/day, respectively. A 40 mg/day dose showed an objective response only in postmenopausal pts with estrogen receptor (ER) positive or unknown cancer. At a dose of 60 mg/day, some of the responding cases were premenopausal pts or pts with ER(-) cancer. In pts with cancer relapse during adjuvant therapy or in those with previous therapy and/or radiation, response rates were 25.0% (2/8), 0% (0/4), 13.5% (5/37) and 10.3% (4/39) at doses of 40, 60, 120 and 240 mg/day, respectively. Response was more frequent in pts with ER (+) cancer than with ER (-) cancer. The response rates in pts with previous therapy including tamoxifen (TAM) except medroxyprogesterone (MPA) were 14.3% (4/28) at a 120 mg/day dose and 6.1% (2/33) at a 240 mg/day dose. In pts with previous therapy including TAM, MPA and other antitumor agents, the rate was 18.2% (2/11) at a 120 mg/day dose. Side effects such as elevation of GOT, GPT and serum Ca level, decrease of hemoglobin, anorexia, nausea/vomiting, fatigue, dizziness and hot flush were observed. These side effects were moderate in grade and reversible. Dose dependency of side effects was not clearly observed in grade and incidence. From these results, NK 622 is expected to be a safe drug with efficacy in first line therapy at a dose of 40 mg/day and in second or third line therapy at a dose of 120 mg/day.
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PMID:[Phase II study of NK 622 (toremifene citrate) in advanced breast cancer, a multicentral cooperative dose finding study]. 842 89

TT-62 is a new derivative of FdUMP, which is the active metabolite of 5-FU. A phase I clinical study of TT-62 was conducted by a cooperative study. The same patients received single and 2-week oral administration of TT-62. Starting from 60 mg/m2 (1n), the dose was escalated to 420 mg/m2 (7n). In the single administration, the maximum tolerated dose (MTD) could not be determined. In the 2-week administration, MTD was 420 mg/m2, and the dose limiting factor was gastro-intestinal disturbances such as anorexia, nausea, vomiting and diarrhea. Increases in GOT.GPT and a decrease in hemoglobin content were observed. After administration was stopped all side effects disappeared. TT-62 was detected mainly in the plasma, while trace amounts of 5-FU and FUdR were also detected. TT-62 was excreted mostly in the urine, as alpha-fluoro-beta-alanine (FBAL). The cumulative urinary excretion of FBAL was about 80% of the total dose, and the oral absorption of TT-62 was thus thought to be good.
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PMID:[Phase I clinical study of TT-62. Research group of TT-62]. 843 62

Administration of tetracycline was believed to be associated with an adverse drug reaction in a cat. Clinical signs consisted of anorexia, ptyalism, and signs of depression. The most noticeable biochemical abnormality was a markedly high serum alanine transaminase activity. Treatment consisted of vitamin E and selenium injections and feeding via a gastrostomy tube. Abnormalities noticed on histologic examination of hepatic tissue were centrilobular fibrosis, mild diffuse cholangiohepatitis, and mild hepatic lipidosis. The lipidosis was believed to have resulted from tetracycline administration, whereas the more chronic lesions (hepatic fibrosis and mild cholangiohepatitis) were believed to have resulted from preexisting, subclinical hepatic disease. Because serum alanine transaminase activity returned to reference ranges and the anorexia and ptyalism resolved with cessation of tetracycline administration, these abnormalities were believed to have represented an adverse drug reaction. Treatment of the cat with vitamin E and selenium was instituted on the basis of reported preventive and therapeutic effects in albino rats with tetracycline-induced hepatic lesions. Whether these compounds had any role in accelerating clinical recovery in this cat is uncertain.
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PMID:Increased alanine transaminase activity associated with tetracycline administration in a cat. 844 8

Medical records and histologic sections of 40 cats with acute pancreatitis were reviewed. Two distinct groups of cats with pancreatitis were established by histologic analysis of tissue. Group 1 (32 cats) had acute pancreatic necrosis (APN). Group 2 (8 cats) had suppurative pancreatitis. Ages of affected cats ranged from 3 weeks to 16 years. The majority consisted of indoor cats of the Domestic Short-Haired breed but Siamese cats were over-represented relative to the general population (P < 0.05). Twenty-two percent of cats were obese and 57% were underweight. Thirty-eight percent of cats had acute disease. In the other cats, two stages in the progression of the disease were evident: (1) anorexia, weight loss, and lethargy, followed by (2) acute deterioration, development of shock, and a moribund state, despite fluid therapy. The most common clinical signs were severe lethargy (100%), reduced appetite (97%), dehydration (92%), and hypothermia (68%). The initial hemogram occasionally showed a neutrophilia (30%) and anemia (26%) but packed cell volume (PCV) decreased markedly to the extent that 55% of cats were anemic terminally. Serum biochemical abnormalities included increased activities of ALT (68%) and ALP (50%), and increased concentrations of bilirubin (64%) and cholesterol (64%). Cats with APN were hyperglycemic (64%), glycosuric (60%) and ketonuric (20%), whereas cats with suppurative pancreatitis tended to be hypoglycemic (75%). Renal failure and electrolyte abnormalities were mild or infrequent except for hypokalemia (56%). This study characterizes a severe necrotizing pancreatitis in the cat similar to that reported in other species, and a histologically distinct suppurative pancreatitis.
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PMID:Acute necrotizing pancreatitis and acute suppurative pancreatitis in the cat. A retrospective study of 40 cases (1976-1989). 1146 88

Anorexia, weight loss, fatigue, symptoms of alcohol withdrawal and hepatomegaly are common early presenting signs and symptoms of alcohol abuse. The clinical diagnosis of alcoholic hepatitis can be made in alcoholics with associated fever, leukocytosis, jaundice and tender hepatomegaly. Associated laboratory abnormalities may include leukocytosis or leukopenia, anemia, a prolonged prothrombin time and elevated liver enzymes, including aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin. An AST-to-ALT ratio greater than 2 is common in patients with alcoholic hepatitis. Liver biopsy may be required to establish the diagnosis and to identify other pathology, such as cirrhosis. Histologic diagnosis of alcoholic hepatitis requires the presence of liver cell damage, an inflammatory infiltrate and fibrosis. Biopsy-proven cirrhosis with alcoholic hepatitis or a significantly elevated total bilirubin level and prolonged prothrombin time are associated with a worse prognosis. Abstinence from alcohol, nutritional supplementation and corticosteroids are the mainstays of treatment for severe alcoholic hepatitis.
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PMID:Alcoholic hepatitis. 846 12

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant recipients. To assess the efficacy and the safety of therapy with interferon alpha (IFN alpha) in such a population we conducted a prospective study where 16 kidney transplant recipients with chronic hepatitis C received recombinant IFN alpha 3 million units three times weekly scheduled for 24 consecutive weeks. All the patients had stable renal function for at least 1 year (mean serum creatinine 125.4 +/- 41 mumol/l). Fifteen patients had a positive HCV viraemia at the beginning of the study. In 15 patients serum alanine aminotransferase (ALT) levels decreased rapidly and normalized (48 +/- 44 vs 98.5 +/- 46 IU/l; P = 0.0044). ALT remained in the normal range as long as IFN alpha was continued. Serum levels of gamma glutamyl transpeptidase decreased from 129.75 +/- 111.2 to 88 +/- 85 IU/l; P = 0.012). After discontinuation of IFN alpha therapy seven responders relapsed within 1-9 weeks. HCV viraemia assessed 1 month after the end of IFN alpha therapy remained positive in all the patients who scored positive at the beginning, i.e. 15. Side effects of IFN alpha (fatigue, anorexia, weight loss) were frequent leading to four patients dropping out of the study. The haematological tolerance was moderate. The major concern was the increase in serum creatinine (162.5 +/- 57.6 vs 125.4 +/- 41 mumol/l; P < 0.05). In fact only six patients experienced renal failure occurring 45-168 days after the beginning of IFN alpha. Kidney transplant biopsies showed oedema, scarce scattered interstitial inflammatory cellular infiltration and moderate mesangial hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preliminary results of treatment of chronic hepatitis C with recombinant interferon alpha in renal transplant patients. 852 7

Interferon-alpha-2a is a recombinant interferon with antiviral, antitumour and immunomodulatory properties. Clinical studies have demonstrated that the drug offers therapeutic benefit in patients with some forms of chronic viral hepatitis. Remission, as measured by clearance of viral DNA and hepatitis B 'e' antigen (HBeAg), and normalisation of serum alanine aminotransferase levels, is observed in approximately 30 to 45% of patients with chronic hepatitis B receiving interferon-alpha-2a (2.5 to 18MU administered 3 times/week); about 5 to 15% of untreated controls remit spontaneously every year. Complete recovery [with loss of hepatitis B surface antigen (HBsAg)] is usually noted in < 20% of treated individuals. Similar response rates have been reported in the relatively small number of children evaluated to date. Although numerous studies have shown that interferon-alpha-2a (at various dosages) induces biochemical amelioration of chronic hepatitis C in approximately 50 to 75% of patients, relapse is common. Thus, long term remission may only be observed in about 15 to 30% of treated patients. On the other hand, this disorder remits spontaneously in only a few patients. The role of interferon-alpha-2a in the treatment of chronic hepatitis D remains unclear. Although preliminary data suggest it may be beneficial, cessation of therapy is generally followed by relapse. As with other types of interferons, most patients receiving interferon-alpha-2a experience an 'influenza-like' syndrome, which tends to diminish with continuing therapy. Other effects such as fatigue, lethargy, anorexia and weight loss are usually dose-limiting. Serum neutralising antibodies develop in approximately 10 to 20% of treated patients. Thus, although response rates are less than optimal, interferon-alpha-2a is a drug of first choice amongst the limited therapeutic options available for the management of well-compensated chronic viral hepatitis B or C.
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PMID:Interferon-alpha-2a. A review of its pharmacological properties and therapeutic use in the management of viral hepatitis. 858 31

Three calves received 10 g Riedeliella graciflora dry leaves/kg body weight by gavage. Blood samples were taken immediately before plant administration and at 2, 4, 6, 12 and 24 hours later; serum ALT, AST, AP, TB, urea and creatinine were determined. After R graciflora administration, the calves had anorexia, profound depression and recumbency prior to death. Creatinine levels increased markedly until death. Severe tubular nephrosis was consistently observed.
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PMID:The acute toxicity of Riedeliella graciflora in calves. 859 33

To evaluate the frequency, pattern, and severity of liver function test abnormalities in patients with Lyme disease associated with erythema migrans (EM), 115 individuals with no other identifiable cause for liver function test abnormalities who presented with EM between July 1990 and September 1993 were prospectively evaluated. For individuals with abnormal liver function tests, common causes of hepatitis, including hepatitis A, B, and C, were excluded. A local control group was used for comparison. Forty-six (40%) patients had at least one liver test abnormality, and 31 (27%) had more than 1 abnormality compared with 19 (19%) and 4 (4%) of controls, respectively (P < .01 for each comparison). gamma-Glutamyl transpeptidase (28%) and alanine transaminase (ALT) (27%) were the most frequently elevated liver function tests among Lyme disease patients. Anorexia, nausea, or vomiting was reported by 30% of patients, but did not occur more frequently in patients with elevated liver function tests compared with those with normal values. Patients with early disseminated Lyme disease were more likely to have elevated liver function studies (66%) compared with patients with localized disease (34%) (P = .002). After antibiotic treatment, elevated liver function tests improved or resolved in most patients. Liver function test abnormalities are common in patients with EM but were mild, most often not associated with symptoms, and improved or resolved by 3 weeks after the onset of antibiotic therapy in most patients.
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PMID:Liver function in early Lyme disease. 867 58

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.
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PMID:[LY188011 phase I study. Research Group of Gemcitabine (LY188011)]. 868 15


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