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 prospective evaluation was conducted of 94 unselected patients ("all comers") with biopsy-proven Child's class C cirrhosis (93% alcoholic) and endoscopically proven acutely bleeding esophageal varices who underwent emergency portacaval shunt (EPCS) (85% side-to-side, 15% end-to-side) within 8 hours of initial contact (mean, 6.1 hours) during the past 12 years. Follow-up has been 100% and includes all patients for at least 1 year, and 61 patients (65%) for 5 to 12 years. Incidence of serious risk factors on initial contact was: ascites, 97%; jaundice, 86%; portal-systemic encephalopathy including past history, 71%; severe muscle wasting, 96%; alcohol ingestion within 7 days, 66%; delirium tremens, 16%; serum albumin, less than or equal to 2.5 g/dL 76%; indocyanine green dye retention greater than or equal to 50% in 45 minutes, 66%; serum glutamic-oxaloacetic transaminase greater than or equal to 100 units/L, 60%; hyperdynamic cardiac output greater than or equal to 6 L/minute, 98%. Mean Child's point score was 13.7 out of a maximum of 15. EPCS reduced mean corrected free portal pressure from 286 to 23 mm saline, and permanently controlled variceal bleeding in every patient. Of the 94 patients, 74 (80%) left the hospital alive and 68 (72%) survived 1 year. Five-year actuarial survival rate is 64%. Hepatic failure was the main cause of death during initial hospitalization as well as during follow-up, when it was related to continued alcoholism. Portal-systemic encephalopathy, which was present on initial contact in 55% of patients, occurred at some time during follow-up in 18.7%, but was recurrent and required dietary protein restriction in only 9%, all of whom had resumed alcoholism. The low incidence of portal-systemic encephalopathy was attributable to the lifelong program of follow-up with regular dietary counseling and continued emphasis on both protein restriction to 60 g/day and abstinence from alcohol. Abstinence was sustained in 69%, liver function improved in 82%, general health was judged excellent or good in 73%, and Child's risk class converted to class B in 73% and class A in 21%. Excluding retirees because of age, 42% were gainfully employed or engaged in full-time housekeeping. Long-term shunt patency was documented in 100% of survivors by yearly angiography or Doppler ultrasonography. It is concluded that EPCS within 8 hours of initial contact permanently controls variceal hemorrhage and results in prolonged survival and a life of acceptable quality in many alcoholic cirrhotic patients in Child's class C.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Is portal-systemic shunt worthwhile in Child's class C cirrhosis? Long-term results of emergency shunt in 94 patients with bleeding varices. 141 75

Hepatic encephalopathy is a neuropsychiatric syndrome, which can occur in the clinical course of acute (fulminant) or chronic hepatic failure of various aetiology; reversible metabolic abnormalities without neuronal structural changes are frequently found in this condition. High blood ammonia levels, an imbalance between plasma concentrations of branched-chain and aromatic amino acids, false neurotransmitters and neurotransmitters receptor changes in CNS are the commonly recognized pathogenetic mechanism of this syndrome. Protein malnutrition is a frequent occurrence in liver cirrhosis, especially of alcoholic aetiology. High protein diets may precipitate hepatic encephalopathy; protein restriction leads to malnutrition and enhances a negative nitrogen balance. Several clinical studies have shown that vegetable proteins are tolerated better than animal in patients with liver cirrhosis and chronic portal-systemic encephalopathy: encephalopathy index is usually lower after vegetable-protein than animal-protein diet. The favourable therapeutic effect of vegetable diets on nitrogen metabolism can be mainly accounted for by the increased intake of dietary fibers and increased incorporation and elimination of nitrogen in fecal bacteria. Mixture of amino acids enriched with branched-chain amino-acids may contribute to maintain a positive nitrogen balance and minimize muscle wasting in cirrhotics.
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PMID:[The dietary protein contribution and hepatic encephalopathy in cirrhosis]. 162 17

1. We investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indices of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with cirrhosis and in 11 healthy control subjects. Whole-body protein turnover was also measured using L-[1-13C]leucine. 2. Leg efflux of tyrosine was 45% greater in cirrhotic patients than in normal control subjects [-6.5(1.4 to -19.1) vs -4.2(-2.2 to -7.7) mumol min-1 100 mg-1 of leg, median (range), P less than 0.025]. 3-Methylhistidine efflux was not significantly altered. 3. In cirrhosis, whole-body leucine flux was normal but whole-body leucine oxidation was elevated so that whole-body protein synthesis was depressed by 17%. 4. The results indicate the predominant mechanism of muscle wasting in cirrhosis to be a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.
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PMID:Skeletal muscle and whole-body protein turnover in cirrhosis. 216 95

Free amino acid (AA) concentrations in plasma and quadriceps femoris muscle were determined in 19 healthy volunteers and in 16 patients with hepatic cirrhosis and portal hypertension. Nutritional state was impaired as judged by overt muscle wasting (9/16), triceps skinfold thickness less than 70% of normal in 8/14 (57%), and creatinine-height index below 70% in 5/12 (42%). In the plasma of patients the typical amino acid pattern of cirrhosis was to be observed: Elevation of tyrosine and methionine (p less than 0.01), uniform reduction of branched chain amino acids (p less than 0.001) resulting in a decreased molar ratio of BCAA/AAA from 2.85 +/- 0.05 in normal individuals to 1.35 +/- 0.12 in cirrhotics (p less than 0.001). Levels of the gluconeogenic AA glutamine, glutamate, aspartate, alanine, glycine, threonine, serine and lysine were lowered (p less than 0.05). In muscle of cirrhotics, intracellular AA concentrations exhibited a similar pattern with two major exceptions: Tyrosine and phenylalanine were augmented (p less than 0.001). Surprisingly, BCAA levels were altered heterogeneously; those of gluconeogenic BCAA decreased: Valine from 0.34 +/- 0.03 to 0.20 +/- 0.03 mmol/l (p less than 0.001), isoleucine 0.09 +/- 0.01 to 0.05 +/- 0.02 mmol/l. However, the concentration of ketogenic leucine remained unaltered in muscle. Nevertheless, the molar ratio of BCAA/AAA was considerably reduced from 3.70 +/- 0.04 to 0.81 +/- 0.08 (p less than 0.001). Most of the gluconeogenic AA exhibited reduced intramuscular concentrations, but glutamine levels were normal. The pattern of plasma and muscle free AA in hepatic cirrhosis is thus characterized by accumulation of aromatic AA and by depletion of gluconeogenic AA, especially BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristic pattern of free amino acids in plasma and skeletal muscle in stable hepatic cirrhosis. 231 39

1. Muscle protein breakdown in vivo has been studied by measurements of urinary 3-methyl-histidine/creatinine ratios. No differences were found between control subjects and chronic alcoholics either with or without proximal muscle wasting or cirrhosis. 2. Calculation of muscle turnover rates, with the correction of Afting et al. (1981, Biochemical Journal, 200, 449-452) for non-skeletal muscle contributions of 3-methylhistidine and creatinine, showed lower values for alcoholics compared with controls. 3. Tissue activities of a neutral protease, assayed by a novel, rapid and sensitive fluorimetric method, were similar in patients and controls. The activity did not vary with severity of atrophy or the presence of cirrhosis. 4. No evidence was therefore obtained to suggest that alcoholic myopathy is due to increased muscle breakdown.
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PMID:Assessment in vitro and in vivo of muscle degradation in chronic skeletal muscle myopathy of alcoholism. 248 72

Alterations in protein and amino acid metabolism have been postulated to explain the frequent observations of muscle wasting and decreased plasma branched-chain amino acid concentrations in cirrhosis. In order to investigate the changes in protein metabolism, we have measured the rates of leucine turnover and oxidation in six stable, biopsy-proven cirrhotics and six age and sex-matched healthy control subjects after an overnight fast, using [1-13C]leucine tracer. Following a primed constant-rate infusion of [1-13C]leucine, the 13C enrichments of plasma leucine and expired CO2 were used to estimate leucine turnover and oxidation, respectively. Fat-free body mass was estimated from the measurements of total body water as quantified by H2[18O] tracer dilution. The rates of CO2 production and oxygen consumption were measured hourly during the study period, using open-circuit respiratory calorimetry. Urinary urea, ammonia and total nitrogen excretion rates were quantified from timed urine samples. Even though the plasma leucine levels were lower in cirrhotics as compared with controls (100.5 +/- 17.1 vs. 138.3 +/- 20.4 mumoles per liter, mean +/- S.D., p less than 0.001), the rates of leucine turnover were not significantly different in the two groups (89.4 +/- 19.0 vs. 87.8 +/- 19.0 mumoles per kg X hr). In contrast, the rates of leucine oxidation were significantly reduced in cirrhosis (8.1 +/- 2.5 vs. 12.7 +/- 3.1 mumoles per kg X hr, p less than 0.01). When all subjects were considered, the leucine oxidation rate was correlated with plasma leucine concentration (r = 0.62, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Leucine metabolism in stable cirrhosis. 308 96

Since 1963, a prospective evaluation of the emergency portacaval shunt procedure has been conducted in 264 unselected patients with cirrhosis and bleeding varices who underwent operation within 8 hours of admission to the emergency department. Of 153 patients who underwent operation 10 or more years ago, 45 (29 percent) have survived from 10 to 22 years and their current status is known. On admission, 40 percent of the long-term survivors had jaundice, 44 percent had ascites, 13 percent had encephalopathy (with an additional 9 percent with a history of encephalopathy), 29 percent had severe muscle wasting, and 82 percent had a hyperdynamic state. There were 9 Child's class A patients, 33 Child's class B patients, and 3 Child's class C patients. At operation, all patients had portal hypertension which was reduced by the shunt to a mean corrected free portal pressure of 18 mm saline solution. The emergency portacaval shunt procedure permanently controlled variceal bleeding. None of the patients bled again from varices, and the shunt remained patent throughout life in every patient. Encephalopathy did not affect 91 percent of the patients, but was a recurrent problem in 9 percent, usually related to the use of alcohol. Lifelong abstinence from alcohol occurred in 58 percent of the long-term survivors, but 11 percent resumed regular drinking and 31 percent consumed alcohol occasionally. Liver function declined compared with preoperative function in only 18 percent of the patients, almost always because of alcohol use. Ten years after operation, 73 percent of the patients were in excellent or good condition, and 68 percent were gainfully employed or engaged in full-time housework. Comparison of the 10 to 22 year survivors with our early group of 180 patients reported previously and our recent group of 84 patients showed no significant differences in preoperative or operative data. The single factor that appeared to influence long-term survival was resumption of regular use of alcohol. We conclude that the emergency portacaval shunt procedure, by preventing hemorrhage from varices, results in prolonged survival and an acceptable quality of life for a substantial number of patients with advanced alcoholic cirrhosis.
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PMID:Long-term survival after emergency portacaval shunting for bleeding varices in patients with alcoholic cirrhosis. 348 11

The effect of severe liver disease on ranitidine disposition was evaluated by comparing its kinetics in 5 healthy subjects and 11 patients with alcoholic cirrhosis. Cirrhotic patients had severe liver disease as evidenced by the presence of ascites, hepatic encephalopathy, jaundice, muscle wasting, and low serum albumin, but creatinine clearance did not differ significantly between controls and cirrhosis. Following intravenous administration of ranitidine, systemic clearance was decreased in cirrhosis. These decrease may be associated with changes in renal function, and decrease in hepatic metabolism, usually present in patients with severe hepatic failure. The distribution volume of ranitidine was also decreased in cirrhotics, but the difference between patients and controls was not significant. Biological half-life was significantly longer in cirrhotic patients than volunteers. This difference may be due to decrease in total body clearance found in cirrhotic patients. It is concluded that patients with severe liver cirrhosis could have elevated plasma level of ranitidine and that a reduction of ranitidine dosage is warranted in these patients.
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PMID:Ranitidine disposition in severe hepatic cirrhosis. 355 40

To investigate the prediction that urinary cGMP (UcGMP) and cAMP (UcAMP) excretion is altered in a manner consistent with unregulated cell growth in hepatocellular carcinoma (HCC), we studied 31 patients with this disease, 25 without apparent disease, 16 with various hepatic diseases, and 16 with nonhepatic neoplasms. Results were expressed as UcGMP excretion per 100 ml glomerular filtration because reduced creatinine excretion in patients with muscle wasting or renal dysfunction may spuriously elevate UcGMP. UcGMP excretion was elevated in 80% of patients with HCC, 75% of patients with hepatic disease and 68% of patients with other neoplasms. Mean values for UcAMP excretion did not differ significantly from normal values. Plasma and ascitic fluid cGMP concentrations in HCC and hepatic diseases were raised. These results support the hypothesis of a shift in cyclic nucleotide metabolism toward cGMP in malignant diseases. However, UcGMP measurement does not detect progression of cirrhosis to HCC.
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PMID:Cyclic nucleotides in biological fluids in hepatocellular carcinoma. 625 69

A prospective evaluation of emergency protacaval shunt has been conducted in 180 unselected, consecutive patients with cirrhosis and bleeding varices who were operated on between 1963 and 1978. An extensive diagnostic work-up was completed within three to seven hours of admission to the emergency department, and the shunt operation was undertaken within a mean of 7.81 hours. A program of lifelong follow-up was conducted such that the current status of 97% of the patients is known. On each patient, 220 categories of data were collected and entered into a computer program for analysis. On admission, 49% of the patients had jaundice, 53% had ascites, 19% had encephalopathy, 30% had severe muscle wasting and 100% had abnormal BSP retention. Administration of a bolus dose of vasopressin by the systemic intravenous route temporarily controlled the varix hemorrhage in 95% of patients, and emergency shunt permanently controlled the bleeding in 98%. Maximum perfusion pressure in the portal vein prior to shunt did not correlate with survival rate or incidence of encephalopathy after shunt. The operative survival rate was 58%, the five-year actuarial survival rate is 38% and the 12-year actuarial survival rate is 30%. Encephalopathy was observed in 31.5% of the patients, but was severe enough to require chronic dietary protein restriction in only 7%. The portacaval shunt remained patent in 99% of patients. Of the survivors, 48% abstained from alcohol, 60% resumed gainful employment or housekeeping, and two-thirds were judged to be in excellent or good condition after one and five years. Preoperative factors that adversely influenced survival rate were ascites, SGOT >/= 100 units, BSP retention >50%, hypokalemic alkalosis, blood transfusion requirement >/= 5 L, and consumption of alcohol within seven day[unk] of admission. In comparison with our previous prospective studies, emergency portacaval shunt produced a significantly greater long-term survival rate than either emergency medical therapy or emergency varix ligation, followed by elective shunt. During the past four years, 80% of 49 unselected patients have survived emergency shunt, and the four year actuarial survival rate is 69%.
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PMID:Long-term results of emergency portacaval shunt for bleeding esophageal varices in unselected patients with alcoholic cirrhosis. 696 81


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