Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on uncontrolled observations, we have proposed ursodeoxycholic acid (UDCA) as a novel therapeutic approach in primary biliary cirrhosis (PBC). To confirm and extend our original findings, we have designed a double-blind multicentre randomized clinical trial. An interim analysis was planned at 6 months, involving all subjects included in the trial, with a final analysis at 2 years. The UDCA-PBC trial began in June 1987 and will be completed in March 1990. Seventy patients were randomized to receive UDCA and 68 a placebo. The two groups were well matched with respect to age, sex, duration and prevalence of symptoms and histologic severity (50% of the UDCA group had stage III-IV disease vs. 37% of the placebo group). During the first 6 months of follow-up, six patients withdrew from the trial. At 6 months, the proportion of patients with jaundice was significantly lower (p less than 0.01) in UDCA recipients than in the placebo group. There was a similar decrease in the proportion of patients with pruritus and fatigue in both groups. The following laboratory test values were significantly lower in UDCA recipients than in the placebo group after 6 months of therapy: serum bilirubin, alkaline phosphatase, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyltranspeptidase activities (p less than 0.001), cholesterol (p less than 0.003) and IgM levels (p less than 0.03). The results of this interim analysis confirm and extend the biochemical data provided by our previous pilot study. However the final analysis of the trial is necessary for a definitive assessment of the safety and efficacy of UDCA therapy in PBC.
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PMID:Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Interim analysis of a double-blind multicentre randomized trial. The UDCA-PBC Study Group. 197 19

The impact of alcohol and marijuana abuse on the physical health and nutritional status of adolescents has not been well documented. The health consequences of alcoholism and chemical abuse in adults may not relate to the pediatric population. Forty-nine adolescent boys (mean age 15.8 years) with varying degrees of alcohol and marijuana use by self-report were evaluated as to their general health, pubertal development and nutritional status using health and dietary history, physical examination, anthropometrics, and biochemical assays of liver function and tissue nutrients. Thirteen (27%) were alcohol and marijuana abusers, 20 (41%) marijuana abusers, and 16 (32%) nonusers. There were significant differences between alcohol and marijuana abusers and marijuana abusers compared to nonusers with respect to endorsing symptoms of nutritional deficiency (muscle weakness, bleeding gums, tiredness, etc) (P less than .001). There were no significant differences between subgroups in other nutritional measures except plasma zinc concentration which was low in marijuana abusers (mean 85 micrograms/dL). All adolescents reported consuming adequate nutrients, although alcohol and marijuana abusers reported eating more snack foods and less fruit, vegetables, and milk than other groups. There were no significant differences in hematologic status (complete blood cell count, transferrin, folate), liver function (gamma-glutamyltranspeptidase), or anthropometric and sexual maturational indices of growth. There were no chronic signs of chemical abuse by physical examinations. It appears that health and nutritional disability from chemical abuse in adolescents relates more to poor dietary habits and symptomatic deterioration in general health than to specific effects on growth or nutritional status. Studies with larger numbers of subjects need to document these findings.
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PMID:Health, developmental, and nutritional status of adolescent alcohol and marijuana abusers. 349 3

We report a young female case of alcoholic liver injury accompanied with various metabolic and endocrinological disorders. A 29 year-old woman was admitted because of general fatigue and hyperlipidemia. She was a heavy drinker. Laboratory data on admission revealed liver dysfunction and hyperlipidemia (type II b) with a quite high serum gamma-glutamyltranspeptidase (gamma GTP) level. The microscopic finding of the liver biopsy specimen showed fatty metamorphosis and ballooning of hepatocytes, and she was diagnosed as heavy alcoholic liver injury. The endocrinological examination revealed the elevated plasma cortisol level, though the urinary 17-hydroxycorticoids (17-OHCS) and 17-ketosteroids (17-KS) excretion and the plasma adrenocorticotropic hormone (ACTH) level were reduced. Cortisol secretion showed the normal circadian rhythm and the normal response to ACTH provocation. The levels of plasma triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were also reduced. These endocrinological and metabolic disorders were normalized in company with recovery of the liver function by temperance, diet therapy and nutritional education. Thus, these abnormalities were considered to be resulted from the alcoholic liver injury and the effect of the ethanol to the hypothalamic-pituitary system.
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PMID:[Alcoholic liver injury accompanied with various metabolic and endocrinological disorders--a case report]. 822 58

AG331 (N6-[4-(morpholinosulfonyl)benzyl]-N6-methyl-2, 6-diaminobenz-[c,d]-indole glucuronate) is a lipophilic thymidylate synthase inhibitor with activity in solid tumor models. On the basis of preclinical data supporting regimens of frequent drug administration, we performed a Phase I trial of AG331 as a 5-day continuous infusion repeated every 3 weeks. Twenty-nine patients were entered at doses ranging from 25 to 1000 mg/m2/day. The major side effects were mild to moderate fatigue, nausea, vomiting, diarrhea, and fever. At doses >/=400 mg/m2, acute reversible elevation of bilirubin, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltranspeptidase was observed. All patients who received >/=600 mg/m2/day experienced elevated alanine aminotransferase. Elevated liver function tests were evident by day 3 of the infusion and had resolved by day 8 in the majority. This toxicity was dose limiting at 1000 mg/m2/day, at which dose two of two patients developed grade 4 reversible hyperbilirubinemia in addition to the enzyme elevations. Serum and urine samples were analyzed by a novel high-pressure liquid chromatography method for the determination of the pharmacokinetics of AG331. Over the 50-1000 mg/m2/day dose range, mean total clearance ranged from 11.6 to 30.0 liters/h/m2, and volume of distribution at steady state ranged from 279.5 to 758.7 liters/m2. These parameters were dose independent over the dose range tested. The harmonic mean terminal half-life of AG331 was 20.2 h. Less than 5% of an AG331 dose is eliminated unchanged in the urine. Both the administered dose and exposure to the drug were related to the changes in bilirubin and aminotransferase blood levels. Evidence for inhibition of thymidylate synthase was obtained at doses ranging from 100 to 1000 mg/m2 in seven patients; plasma deoxyuridine concentrations at end-infusion were 1.8-3.8-fold higher than pretreatment values. Because of the nature of toxicity on this schedule, more extensive Phase II evaluation is not recommended, although an AG331 dose of 800 mg/m2/day for 5 days is tolerable. Exploration of less frequent dose administration is under way.
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PMID:Phase I trial of the thymidylate synthase inhibitor AG331 as a 5-day continuous infusion. 981 17

We encountered a case of left hepatic duct cancer that developed 7 years after surgical resection of early-stage adenocarcinoma of the gallbladder. A 65-year-old woman was hospitalized with high fever and general fatigue. She also had elevated serum levels of alkaline phosphatase, gamma-glutamyltranspeptidase, and carbohydrate antigen 19-9. Seven years earlier, she had undergone extended cholecystectomy and resection of the extrahepatic bile duct for early-stage mucinous adenocarcinoma of the gallbladder. Conventional examinations did not reveal any responsible lesions. Magnetic resonance (MR) cholangiography, however, showed a tumor obstructing the left hepatic duct, and dynamic MR images revealed multiple foci of bacterial abscess in the liver. Surgically resected tissue again revealed mucinous adenocarcinoma. The present case is rare in that metachronous mucinous adenocarcinoma of the biliary system occurred after a long interval. This case suggests the usefulness of MR imaging in the postsurgical monitoring of patients with gallbladder carcinoma.
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PMID:Usefulness of MR imaging in the postsurgical monitoring of gallbladder cancer in a patient with bile duct cancer that developed 7 years after resection of mucinous adenocarcinoma of the gallbladder. 1175 53