Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A novel, simple, clinically useful quantitative liver function test, called the galactose single point (GSP) method, was developed by measurement of galactose blood concentration 1 h after galactose was administered (0.5 g/kg). It was quickly infused intravenously in 55 normal healthy volunteers, 73 patients with chronic hepatitis (CH), 36 with cirrhosis and 41 with hepatocellular carcinoma (HCC). Patients with CH diagnosis were assessed by liver biopsy. Cirrhosis was diagnosed by histological examination or a chronic hepatitis history with esophageal varices or ascites, whereas HCC was diagnosed either histologically, or cytologically proved, or as implied in the 'one imagine study' being positive with AFP > 300 ng/dl. Highly significant galactose blood levels were observed between normal healthy volunteers and patients 50, 60 and 70 min after galactose was administered. Galactose elimination capacity (GEC), modified GEC (MGEC) and consecutive GSP tests were performed in 6 healthy volunteers for 2 days. 0.64-16.87% variation was observed for each subject. The significant differences (p < 0.001) in average GSP values were 247 +/- 18.1, 422 +/- 27.3, 629 +/- 42.8 and 579 +/- 43.6 micrograms/ml for normal healthy volunteers, CH, cirrhosis and HCC patients, respectively. Highly significant correlations (p < 0.001) were obtained among GSP, GEC and MGEC for all patients. Positive correlations were observed between GSP, GEC, MGEC and AST (serum aspartate aminotransferase), ALT (serum alanine aminotransferase), serum bilirubin, albumin, prothrombin time and r-globulin. According to results obtained from 202 normal healthy volunteers and patients, the GSP method may be a simple, clinically useful quantitative measurement of liver function for the determination of a patient's residual liver function, the prognosis of liver function for patients with cirrhosis, postoperational follow-up and, finally, the timing of a liver transplant.
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PMID:Assessment of liver function using a novel galactose single point method. 133 11

A block in the transsulfuration pathway has previously been suggested in cirrhosis on the basis of increased fasting methionine concentrations, decreased methionine elimination and low levels of methionine end products. To date, methionine elimination has never been studied under controlled steady-state conditions, and the relation of the severity of liver disease to impaired methionine metabolism has not been clarified. We measured methionine plasma clearance in 6 control subjects and in 12 patients with cirrhosis during steady-state conditions obtained by a primed, continuous methionine infusion. In the presence of high-normal fasting methionine concentrations (range = 14 to 69 mumol.L-1 in controls and 26 to 151 mumol.L-1 in cirrhotic patients), methionine plasma clearance was reduced in cirrhotic patients (2.25 +/- S.D. 0.43 ml.sec-1 vs. 2.86 +/- S.D. 0.43 ml.sec-1 in controls; p less than 0.05), whereas methionine half-life was increased (282 +/- 90 min vs. 187 +/- 25 min in controls; p less than 0.05). Fasting methionine significantly correlated with methionine clearance. The infused methionine was not degraded to urea to any significant extent in cirrhotic patients, whereas a threefold increase in urinary urea nitrogen excretion rate was observed in controls. Similarly, taurine concentrations significantly increased both in plasma and in the urine in controls but not in cirrhotic patients. In cirrhotic patients methionine plasma clearance significantly correlated with galactose elimination capacity (r = 0.818) and with the Child-Pugh score (rs = -0.795). The study supports a major role of impaired liver cell function in the reduced metabolism of methionine and decreased formation of methionine end products that occur in cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective methionine metabolism in cirrhosis: relation to severity of liver disease. 137 58

The intravenous administration of fructose in healthy subjects may induce an increase of blood uric acid and the urinary excretion of urate and xanthine as a result of hepatic adenosine triphosphate (ATP) breakdown. These changes are partially reversed by ATP resynthesis. We studied the effect of fructose load (0.5 g/kg body weight) on the products of ATP metabolism, and the interference of fructose on the galactose test in 10 patients with well compensated cirrhosis compared with 10 healthy controls. The fructose and the fructose/galactose loads induced a significantly greater increase of plasma uric acid in cirrhotics than in controls, with a 60 minute peak in the cirrhotics. Urinary excretion of urate and xanthines was significantly increased (p less than 0.001) only in the cirrhotics after the fructose/galactose load. As expected, the galactose elimination capacity (GEC) calculated with the galactose test, was lower in these patients than in controls. Fructose infusion before galactose did not significantly modify the GEC in either of the two groups compared. The higher uric acid increase induced by fructose in the blood of cirrhotic patients seems to be a good marker of the energy crisis of the diseased liver whereby it is unable to efficiently resynthesize ATP from its breakdown products.
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PMID:Hyperuricemia induced by fructose load in liver cirrhosis. 139 16

The effects of vasopressin and of its analogues on liver function, and their possible mechanisms of action, are poorly understood. This study was designed to assess the effect of triglycyl-lysin-vasopressin on liver function, evaluated by two quantitative tests independent of liver blood flow, i.e., indocyanine green intrinsic hepatic clearance and galactose elimination capacity. Indocyanine green intrinsic hepatic clearance and galactose elimination capacity were determined before and after administration of 2 mg triglycyl-lysin-vasopressin to (respectively) 10 and 12 patients with cirrhosis. Eighteen additional patients with cirrhosis were studied before and after infusion of placebo. No significant variation in either test was observed in placebo-treated patients. A significant decrease in indocyanine green intrinsic hepatic clearance, averaging 22%, was observed in patients receiving the drug (p = 0.04). Conversely, galactose elimination capacity remained unchanged after the drug. These results are compatible with the hypothesis that the drug produced a preferential decrease in perfusion in functioning areas of the liver, with relative maintenance of blood flow in non-functioning areas.
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PMID:Effect of triglycyl-lysin-vasopressin on quantitative liver function tests in patients with cirrhosis. 144 77

Various liver function tests were evaluated in regard to a quantitative estimation of the impairment of liver function related to the Child-Pugh classification in 32 patients with cirrhosis. Only the ICG-test revealed significant differences between healthy subjects and cirrhotic patients in stadium Child A, B and C. When ICG-dye retention values were plotted as a function of the individual score units of the Child-Pugh classification, a linear relationship with a correlation coefficient of 0.7 was obtained. In contrast to the ICG-test, the MEGX- and galactose elimination capacity (GEC)-test as well as static parameters of liver function (cholinesterase activity, prealbumin concentration, coagulation factor V and VII) resulted in less significant differentiation of the various Child classes. The MEGX-test, GEC, concentration of prealbumin, coagulation factor V and VII were only weakly correlated to the score units of the Child-Pugh index. The results of this study indicate that of all evaluated parameters only the ICG-test is suitable for objective and graduated analysis of liver function in patients with cirrhosis.
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PMID:[Liver function tests in a clinical comparison]. 147 85

Congenital dyserythropoietic anaemia type II, or HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum lysis test) is a genetic disease caused by membrane disorganization of erythroid cells. The primary defect of this disease lies in the gene encoding enzyme(s) which is responsible for the biosynthesis of Asn-linked oligosaccharides chains of glycoproteins (Fukuda et al, 1990). In order to know whether this gene defect affects the glycosylation in the cells other than the erythroid cells, the carbohydrate structures of the transferrin isolated from the sera of HEMPAS patients were analysed. Fast atom bombardment mass spectrometry analysis showed the presence of high mannose type and hybrid type oligosaccharides in the HEMPAS transferrin which is in contrast to the complex-type oligosaccharides found in the normal transferrin. The results strongly suggest that biosynthesis of Asn-linked oligosaccharide chains in HEMPAS hepatocytes is disturbed. As a result, the serum glycoproteins with incompletely processed carbohydrates are circulating in the plasma in HEMPAS patients, but they must have been absorbed by the cells in the liver and the reticuloendothelial cells. Upon intravenous infusion into rats, as much as 30% of the HEMPAS transferrin was cleared from the plasma circulation. The majority of the HEMPAS transferrins was taken up by the liver, and transferrin was distributed both in the hepatocytes and the Kupffer cells. The presence of enormous amounts of aberrantly glycosylated serum glycoproteins may lead to the liver cirrhosis and secondary tissue siderosis seen in HEMPAS patients.
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PMID:Incompletely processed N-glycans of serum glycoproteins in congenital dyserythropoietic anaemia type II (HEMPAS). 148 62

The efficacy of urea synthesis as measured by functional hepatic nitrogen clearance (i.e., the relation of urea synthesis rate to blood alpha-amino nitrogen concentration) was studied before and after diet protein supplementation in six healthy subjects and five patients with stable cirrhosis (galactose elimination capacity about 60% of control). Daily protein intake was increased for 14 days by a protein-enriched liquid from (mean +/- S.D.) 1.01 +/- 0.32 g/kg body wt. to 1.62 +/- 0.31 g/kg body wt in the control subjects, and from 0.69 +/- 0.21 g/kg body wt. to 1.50 +/- 0.15 g/kg body wt. in the patients with cirrhosis. This increased the hepatic nitrogen clearance from 27 +/- 10 l/h to 39 +/- 15 l/h in the control subjects (p less than 0.05) and from 15 +/- 6 l/h to 21 +/- 7 l/h in the cirrhosis patients (p less than 0.05). There was no effect on the galactose elimination capacity in any group. Compared to the control subjects, the response in hepatic nitrogen clearance relative to the increase in protein intake was reduced by 60% in the patients. Basal glucagon was 75% higher in the patients and increased by 50% during high protein intake (p less than 0.05), but did not parallel the increase in hepatic nitrogen clearance, and it did not change in the control subjects. The study shows that an increase in protein intake selectively increases liver function with regard to disposal of amino nitrogen; the mechanism is qualitatively intact but quantitatively deficient in patients with cirrhosis of the liver, and does not seem to depend on glucagon.
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PMID:Effects of an increase in protein intake on hepatic efficacy for urea synthesis in healthy subjects and in patients with cirrhosis. 150 Jun 87

Quantitative liver function tests are based on the clearance concept and measure the plasma disappearance of a test compound such as galactose. Metabolism is inferred to be predominantly hepatic, and usually no knowledge is obtained of the true time course of metabolite formation. Dynamic 31phosphorus magnetic resonance spectroscopy after intravenous administration of fructose directly measures hepatic sugar metabolism. To determine the feasibility and the utility of 31P magnetic resonance spectroscopy, we studied the responses of six healthy subjects and nine patients with nonalcoholic cirrhosis to a fructose load. Results were related to the impairment of hepatic function assessed by the galactose-elimination capacity test. Liver spectra were acquired in a 1.5 T whole-body nuclear magnetic resonance unit with a surface coil (9-cm diameter) placed ventrally on the liver; the one-dimensional chemical-shift imaging technique was used to obtain spectra from tissue slices parallel to the surface coil. After a basal spectrum had been obtained, fructose (250 mg/kg) was injected intravenously, and further spectra were collected sequentially every 6 min for 1 hr. Formation of monophosphate esters (9% +/- 5% vs. 20% +/- 8% of total area; p less than 0.01) and utilization of inorganic phosphate (5% +/- 4% vs. 11% +/- 3% of total area; p less than 0.005) were markedly decreased in cirrhotic patients. These measures correlated with the severity of the impairment of liver function measured by the galactose-elimination capacity (r = 0.53 to 0.69; p less than 0.05). We conclude that dynamic 31P magnetic resonance spectroscopy is a safe, clinically feasible test that allows detailed insights into biochemical events in liver disease.
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PMID:Alterations in hepatic fructose metabolism in cirrhotic patients demonstrated by dynamic 31phosphorus spectroscopy. 156 25

Visual event-related P300 potentials, conventional visual evoked potentials, and psychometric tests were applied to patients with noncirrhotic chronic liver disease and to clinically nonencephalopathic and encephalopathic cirrhotics to compare their diagnostic efficacy in detecting early portosystemic encephalopathy (PSE). Sixty-four investigations were performed in 58 patients. The latencies of the P300 parameters were significantly longer in both the encephalopathic and nonencephalopathic cirrhotics than in the noncirrhotics, indicating distinctly abnormal cortical processing of visual stimuli in cirrhotic patients. The visual P300 potentials showed the highest sensitivity and specificity for grade I PSE. Abnormal P300 test results were also found in 78% of the clinically nonencephalopathic cirrhotics, while psychometric tests showed abnormalities in only 41%. The P300 latencies were similar in alcoholic and nonalcoholic cirrhotics. Significant inverse correlations were found between the P300 latencies and measures of quantitative liver function such as galactose-elimination capacity and aminopyrine breath test. It is concluded that visual event-related P300 potentials are a sensitive index of subclinical and grade I PSE. Furthermore, the degree of cognitive dysfunction detected by this method in patients with liver cirrhosis appears to be related to the reduction in hepatic metabolic capacity.
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PMID:Visual event-related P300 potentials in early portosystemic encephalopathy. 161 38

Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed analog ligand to ASGP-R. Fourteen human subjects were studied: three normal volunteers, one with chronic hepatitis, 6 with liver cirrhosis, and 4 with hepatocellular carcinoma associated with liver cirrhosis. The receptor index parameter (LHL15), was obtained from the liver and heart time-activity data as the ratio of radioactivity of the liver over that of the liver plus heart at 15 min after intravenous injection of 1 mg of TcGSA. Means +/- standard deviations of LHL15 in normal volunteers (3 cases), patients with mild (4 cases), moderate (2 cases), and severe liver damage (5 cases) were 0.933 +/- 0.006, 0.789 +/- 0.045, 0.723 +/- 0.033, and 0.488 +/- 0.094, respectively. The difference between the mean values of each group was statistically significant (P less than 0.05). LHL15 correlated well with classical indicators for hepatic functional capacity such as serum albumin level, serum bilirubin level, prothrombin time, ICG R15 or Child-Turcotte criteria score. Our preliminary experiences of high correlations of TcGSA functional imaging data with clinical data suggest that the dynamic data using this receptor-binding radiopharmaceutical provides invaluable information with regard to liver function, and thus, the TcGSA study is potentially a noninvasive practical tool to measure functioning hepatocyte mass.
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PMID:Functional hepatic imaging with receptor-binding radiopharmaceutical: clinical potential as a measure of functioning hepatocyte mass. 166 53


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