Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effective liver blood flow is the portion of total flow that perfuses functional sinusoids and is available for metabolic exchange. Clearance of galactose from blood at concentrations below 10 mg/dl (0.555 mmol/l) measures this index and is calculated during continuous infusion of 5% D-galactose at a rate of 50 mg/min. The low galactose concentrations are measured accurately by a new fluorometric assay, which gives a precision +/- 0.2 mg/dl (0.011 mmol/l). In healthy people, plasma galactose clearance was 1366 +/- 172 ml/min, and hepatic extraction was 95%. Clearance in cirrhotics depends on the stage of their disease: in a stable group of patients with advanced cirrhosis, clearance was 835 +/- 87 ml/min with hepatic extraction ranging from 60% to 95%. The day-to-day coefficient of variation was 4.5%. Direct comparison with flow-probe liver blood flow measured in 11 normal dogs showed that galactose clearance was not significantly different. These findings support the hypothesis that galactose clearance correlates with effective liver blood flow.
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PMID:Effective liver blood flow: determination by galactose clearance. 682 99

The disposition of zomepirac was investigated in 18 patients with various liver diseases and in 10 healthy normal subjects in order to further test the hypothesis that glucuronidation of drugs may be spared in liver disease. Severity of the liver disease was assessed by the galactose elimination capacity. Following oral administration of zomepirac (200 mg), plasma and urinary drug concentrations were measured by high-pressure liquid chromatography. Urine was assayed before and after alkaline hydrolysis. The apparent oral clearance of zomepirac was 3.7 +/- S.D. 1.2, 3.0 +/- 0.8, and 1.8 +/- 0.6 ml . min-1 . kg-1 in normal subjects, patients with mild liver disease, and cases with cirrhosis, respectively. In patients with liver disease, the reduction in zomepirac clearance was significantly correlated with the abnormalities in galactose elimination capacity (r = 0.83, n = 18), suggesting that the functioning liver cell mass was the major determinant of the rate of zomepirac disposition. These results are not consistent with the original hypothesis but suggest that--in contrast to ether-glucuronidation--ester-glucuronidation may be abnormal in liver disease. Dosage adjustments may, therefore, be necessary in patients with cirrhosis of the liver.
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PMID:Abnormal glucuronidation of zomepirac in patients with cirrhosis of the liver. 684 Jun 87

Because of its specific hepatic degradation tryptophan was orally administered (50 mg/kg) to patients with various chronic liver diseases (n = 30) and to healthy volunteers (n = 8) as a test for hepatic function. The plasma half life of tryptophan was determined between 4 and 8 h after the amino acid load. It was found that in patients with cirrhosis (n = 25) the half life of tryptophan was prolonged to 4.7 +/- 0.4 h (means +/- SD), compared to 2.0 +/- 0.1 h in the controls. The tryptophan half life also correlated with the plasma concentration of albumin, bilirubin, cholinesterase and prothrombin time in these patients. In addition a significant correlation was observed with the galactose elimination capacity and the 45 min retention of BSP. Thus, the oral tryptophan loading test may be suitable for a more specific determination of functional impairment of the liver in chronic liver disease. In decompensated cirrhotic patients alterations of the tryptophan metabolism seen to be related to indicators of hepatic encephalopathy. The test may therefore be used to assess the degree and risk of hepatic encephalopathy in such patients.
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PMID:[Tryptophan loading test as a function parameter in liver diseases]. 686 62

After oral administration of triamterene to four patients with liver cirrhosis the triameterene (TA) metabolism was altered. The ratio of AUCs of p-hydroxy-triamterene-sulfuric acid ester (OH-TA-ester)/triamterene (TA) was 1.0 +/- 1.0 in cirrhotic patients compared with 7.5 +/- 3.9 in control patients (p less than 0.025). Cumulative urinary excretion of TA was higher and that of OH-TA-ester lower in patients with liver cirrhosis compared with patients without liver disease. The results indicate that the metabolism of TA is influenced by liver cirrhosis. The extent of impairment of the metabolism of TA is correlated to reduced galactose-elimination capacity. This may be an indicator of reduced redox potential of the liver cell.
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PMID:Altered hydroxylation rate of triamterene in patients with liver cirrhosis. 711 22

Quantitative liver function was estimated by determination of the galactose elimination capacity (GEC) in 29 patients with steatosis, 50 with cirrhosis and 42 control patients without clinical history or signs of liver disease. In patients with steatosis and cirrhosis, clinical signs of liver disease were recorded and the most common liver tests were carried out. The degree of histological changes was investigated in needle liver biopsies performed in a close relation to the GEC determinations. A positive correlation between GEC and body weight and body surface area was observed in all three patient groups. GEC (absolute value, per kg body weight and per m2 body surface area) was significantly different (p less than 0.001) between the three groups, but was without diagnostic value due to a broad scattering of results in each group. This may be due to methodological errors in the determination of GEC, but also to the large biological variation in normal man and the pathophysiological conditions in patients with liver disease. Neither in patients with steatosis nor in patients with cirrhosis could significant relations be found between GEC and clinical signs of liver disease or the degree of severity of histological changes assessed semiquantitatively. In patients with cirrhosis but not in patients with steatosis, GEC was significantly correlated with the majority of the most commonly utilized liver tests.
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PMID:The quantitative liver function as measured by the galactose elimination capacity. I. Diagnostic value and relations to clinical, biochemical, and histological findings in patients with steatosis and patients with cirrhosis. 718 May 79

The quantitative liver function, measured by the galactose elimination capacity (GEC), was determined repeatedly in 44 patients with cirrhosis during the course of the disease. After a median observation period of 57 months (range 28-85) 17 had died from liver insufficiency. GEC was found to be of prognostic value, as classification of the patient series on the basis of the median value of two extreme prognostic groups indicated that the survival of patients with GEC greater than 1.37 mmol . min-1 at entry was significantly larger than of patients with GEC below that value (p less than 0.05). The prognostic values of serum albumin and prothrombin were of the same order of magnitude. At repeated examinations during the course of the disease, the survivors always had higher GEC values than those who died from liver insufficiency. Among those who survived and those who died there were patients with both increasing and decreasing GEC values, but no significant changes were observed within the groups. The individual changes in GEC can result from changes in the balance between liver cell necrosis and regeneration, but the possibility cannot be excluded that changes are due to methodological problems in the determination of the quantitative liver function as measured by GEC.
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PMID:The quantitative liver function as measured by the galactose elimination capacity. II. Prognostic value and changes during disease in patients with cirrhosis. 718 May 80

Fasting and postprandial serum concentrations of conjugates of cholic (CCA) and chenodeoxycholic (CCDA) acid measured by radioimmunoassay were compared with morphological changes in percutaneous liver biopsies from 49 patients with alcohol abuse. Sulfobromophthalein (BSP) and galactose elimination tests were also performed, and serum levels of aminotransferases (ASAT, ALAT), glutamyltransferase, alkaline phosphatase, and bilirubin were determined. Raised fasting serum concentrations of CCDA were found in 29 patients (59%), whereas elevated fasting serum levels of CCA were found in 19 patients (39%). The mean fasting and postprandial serum bile acid concentrations were significantly higher in patients with hepatofibrosis and cirrhosis than in those with only fatty changes. The extent of the postprandial rise, however, was variable and not significantly different among the various groups. The BSP elimination test was abnormal in 12 patients (25%) but gave normal results in 2 of the 3 patients with cirrhosis of the liver. The galactose elimination rates differed only between patients with normal liver biopsies and patients with cirrhosis of the liver. The serum enzyme levels were not significantly different between the various morphological groups. It is concluded that determinations of fasting serum bile acids, especially CCDA, give more reliable and sensitive information on the degree of liver damage in alcoholic liver disease than BSP and galactose elimination tests or serum enzyme assays.
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PMID:Serum cholic and chenodeoxycholic acid conjugates and standard liver function tests in various morphological stages of alcoholic liver disease. 720 76

The selective beta 1-adrenoceptor antagonist metoprolol is eliminated primarily by hepatic metabolism and usually less than 5% of an oral dose is excreted unchanged in the urine. The effects of impaired liver function on the pharmacokinetics of metoprolol were studied in 10 patients with hepatic cirrhosis. All subjects were given single doses of 20mg intravenously and 50mg orally on separate days. The mean fraction of the drug available systematically was 84 +/- 10% in patients and 50 +/- 11% in a control group of 6 healthy subjects (p less than 0.05). The total body clearance of metoprolol in the cirrhotics was 0.61 +/- 0.13L/min and in the controls 0.80 +/- 0.11L/min. These values correspond to elimination half-lives of 7.2 +/- 1.2 and 4.2 +/- 1.1 hours, respectively. The differences were not statistically significant. Impaired liver function had no effect on the volume of distribution of metoprolol. Total clearance was weakly but linearly related to galactose clearance (r2 = 0.52; p less than 0.05), and the half-life was related to serum bilirubin (r2 = 0.74; p less than 0.01).
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PMID:Pharmacokinetics of metoprolol in patients with hepatic cirrhosis. 733 59

Clearance of 0-100 mg/L concentrations of galactose from the blood depends on nutrient hepatic blood flow. We can measure such concentrations, which was not previously possible, by a continuous-flow method involving the use of galactose oxidase and peroxidase, the latter being coupled to a fluorogenic substrate, p-hydroxyphenylacetic acid. Interfering substances in the peroxidase reaction are removed by zinc/alkali precipitation. Sensitivity is maximized by using saturating concentrations of the enzymes and substrate. In prepared plasma test samples with galactose concentrations of 10, 40, 70, and 100 mg/L, the within-run CV's ranged from 2.1 to 8.6%, and day-to-day CV's from 2.2 to 17.2%, the largest CV's being for the 10 mg/L concentration. Normal subjects are shown to clear galactose more efficiently than subjects with moderate cirrhosis.
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PMID:Continuous-flow fluorometry of low galactose concentrations in blood or plasma. 735 77

Fourteen patients with liver cirrhosis received oral prednisone or prednisolone (0.3 mg per kg) randomised on two consecutive days. Serum prednisone and prednisolone were measured over the following four hours. Mean serum prednisolone concentration after oral prednisone decreased with impaired liver function estimated by galactose elimination capacity (r = 0.64, P less than 0.03). Mean serum prednisolone concentration after oral prednisone in the seven patients with severely impaired liver function was only 53% (P less than 0.05) of that observed in the seven patients with slightly impaired liver function. Conversely, mean serum prednisone concentration after oral prednisone in the patients with severely impaired liver function was 74% higher (P = 0.05) than in patients with slightly impaired liver function. Mean serum prednisolone after oral prednisolone was independent of liver function. As only prednisolone exerts glucocorticoid activity, our results indicate that prednisolone should be preferred to prednisone in the treatment of patients with impaired liver function.
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PMID:Impaired conversion of prednisone to prednisolone in patients with liver cirrhosis. 736 21


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