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)

1. The urinary excretion of 3-methylhistidine and creatinine was measured in 15 controls and in two groups of 15 patients with liver cirrhosis, with and without severe muscle wasting. All subjects were on a meat-free diet. The values obtained were used to calculate the fractional catabolic rate of myofibrillar protein. 2. In patients without muscle wasting 3-methylhistidine excretion was high in the presence of normal urinary creatinine. The fractional breakdown rate was significantly increased as compared with that of controls. 3. In patients with severe muscle wasting 3-methylhistidine excretion was normal and urinary creatinine was remarkably reduced. The myofibrillar catabolic rate was further increased compared with that of controls and of the other group of patients. 4. 3-Methylhistidine and creatinine excretion allow a complete evaluation of myofibrillar protein degradation, which appears to be remarkably increased in cirrhotic patients. The relevance of increased myofibrillar protein turnover in muscle wasting of subjects with advanced cirrhosis remains to be determined.
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PMID:Myofibrillar protein catabolic rates in cirrhotic patients with and without muscle wasting. 708 59

Portal hypertensive gastropathy is a vascular disorder of the gastric mucosa distinguished by ectasia of the mucosal capillaries and submucosal veins without inflammation. During 1988 to 1993, 12 patients with biopsy-proven cirrhosis (10 alcoholic, 2 posthepatitic) were evaluated and treated prospectively by portacaval shunt for active bleeding from severe portal hypertensive gastropathy. Eleven patients had been hospitalized for bleeding three to nine times previously, and one was bleeding uncontrollably for the first time. Requirement for blood transfusions ranged from 11 to 39 units cumulatively, of which 8 to 30 units were required specifically to replace blood lost from portal hypertensive gastropathy. Admission findings were ascites in 9 patients, jaundice in 8, severe muscle wasting in 10, hyperdynamic state in 9. Child's risk class was C in 7, B in 4, A in 1. Ten of the 12 patients had previously received repetitive endoscopic sclerotherapy for esophageal varices, which has been reported to precipitate portal hypertensive gastropathy. Eight patients had failed propranolol therapy for bleeding. Portacaval shunt was performed emergently in 11 patients and electively in 1, and permanently stopped bleeding in all by reducing the mean portal vein-inferior vena cava pressure gradient from 251 to 16 mm saline. There were no operative deaths, and two unrelated late deaths after 13 and 24 months. During 1 to 6.75 years of follow-up, all shunts remained patent by ultrasonography, the gastric mucosa reverted to normal on serial endoscopy, and there was no gastrointestinal bleeding. Recurrent portal-systemic encephalopathy developed in only 8% of patients. Quality of life was generally good.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of bleeding from portal hypertensive gastropathy by portacaval shunt. 770 94

The results of various biochemical examinations in 14 patients with cirrhosis (6 males and 8 females) with muscle atrophy at the thenar and hypothenar eminence (muscle atrophy group; mAG) were compared with those in 13 patients (8 males and 5 females) with cirrhosis without muscle atrophy at these sites (non-muscle atrophy group; NmAG). All patients were elderly men and women (mAG and NmAG, mean age, 69 +/- 3 years and 60 +/- 7, respectively). In most mAG patients, muscle atrophy was accompanied by palmar erythema. Muscle atrophy was histologically demonstrated by biopsy. Furthermore, electromyography and magnetic resonance study of the cervical spinal cord revealed that the atrophy was of myogenic rather than neurogenic origin. The Child-Pugh score, body mass index and sex hormone level in urine (total 24 h) in the two groups were compared along with the biochemical results. There were no significant differences between the two groups in urine estrogen and testosterone levels. The urinary creatinine excretion was significantly reduced in mAG. The creatine phosphokinese, lactate dehydrogenase isoenzyme and aldolase levels in serum did not differ significantly in the two groups, whereas the serum albumin level was significantly increased in NmAG. Significant differences were observed only for the serum albumin level, age and body mass index. Thus, we consider that palmar muscle atrophy in patients with cirrhosis is not due to hormonal excess in serum, but may be attributable to advanced age and diminished physical strength.
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PMID:Biochemical and clinical study of muscle atrophy at thenar and hypothenar eminences in patients with cirrhosis. 886 73

Type IV glycogenosis (polyglucosan body disease) is a rare congenital autosomal recessive inherited disorder, caused by lack of the branching enzyme (amylo-1,4-1,6 transglucosidase). This deficiency leads to storage of abnormal glycogen (polyglucosan bodies) in the liver and other tissues. The clinical onset of the disease is insidious with non-specific gastrointestinal symptoms followed by progressive hepatic failure. Usually patients die due to hepatic cirrhosis within 4 years. Sometimes myopathy of the heart and skeletal muscle is also present. In these cases, the clinical onset is often later than in typical cases. We report on two brothers with primarily cardiac manifestation and late onset of the disease. The older one started to suffer from progressive dilated cardiomyopathy at the age of 18 years, presenting with severe heart failure, hepatosplenomegaly, ascites and peripheral oedema. He also demonstrated myopathy and muscular atrophy especially of the shoulder and lower limbs. Initially he improved on medical therapy, but one year later severe heart failure recurred followed shortly afterwards by sudden cardiac death. Right heart and skeletal muscle biopsies were performed while he was alive. These, as well as the autopsy, revealed massive accumulation of polyglucosan bodies. In both heart and skeletal muscle, complete branching enzyme deficiency could be proven. His 14-year-old brother showed similar clinical findings of mild dilated cardiomyopathy. His muscle biopsy also revealed polyglucosan body myopathy. Thus, in young patients presenting with congestive cardiomyopathy, type IV glycogenosis has to be considered in the differential diagnosis.
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PMID:A new variant of type IV glycogenosis with primary cardiac manifestation and complete branching enzyme deficiency. In vivo detection by heart muscle biopsy. 888 67

In health, the liver orchestrates the metabolism of proteins and amino acids. When the liver is diseased, the regulation of protein metabolism is frequently disturbed. The manifestations of disturbed protein metabolism in liver disease are varied and change with disease aetiology and severity. The hallmarks of protein and amino acid metabolism in liver disease are lowered concentrations of circulating branched-chain and increased concentrations of circulating aromatic amino acids with concomitantly altered amino acid kinetics. The changes in amino acid kinetics in liver disease are characterized by increased endogenous leucine flux, an indicator of protein breakdown, and leucine oxidation in the post-absorptive state (when calculated using a reciprocal-pool model and normalized for body cell mass). In addition, the increase in whole-body protein synthesis in response to an amino acid infusion may be attenuated in patients with cirrhosis. These changes are often accompanied by clinically apparent muscle wasting, manifest as protein-calorie malnutrition, and associated low levels of hepatically synthesized plasma proteins. While the pathogenesis of these changes in protein and amino acid metabolism has not been elucidated, altered levels of circulating hormones, known to affect protein metabolism, are probably important. Lowered levels of micronutrients and trace metals and elevated levels of cytokines may also play a role.
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PMID:Protein metabolism and liver disease. 902 55

Organized thrombus in the main trunk of the portal vein was encountered in 85 (6.5%) of 1300 patients with cirrhosis and variceal hemorrhage who underwent direct portacaval shunt (PCS). The thrombus was successfully removed with restoration of portal blood flow in all patients by phlebothrombectomy and balloon catheter extraction. Of the 85 patients, 65 were among 400 unselected patients who underwent emergency PCS (16%), and 20 were among 900 selected patients who underwent elective PCS (2%). All patients were closely followed for at least 5 years. Patients with portal vein thrombosis (PVT) had more advanced liver disease than those without PVT, reflected preoperatively in significantly higher (P < 0.01) incidences of ascites (75%), severe muscle wasting (52%), varices of very large size (94%), the hyperdynamic state (94%), severe hypersplenism with a platelet count of less than 50,000/mm3 (92%), and placement in Child's class C (52%). Side-to-side PCS reduced the portal vein-inferior vena cava pressure gradient to a mean of 23 mm saline solution in patients with PVT, similar to the marked pressure reduction obtained in patients without PVT. PCS promptly stopped variceal bleeding in all patients in the emergency PCS group. Permanent prevention of recurrent variceal bleeding was successful in 95% of patients with PVT and more than 99% of patients without PVT. Survival rates were similar in patients with and without PVT. In patients with PVT, survival rates at 30 days and 1, 5, 10, and 15 years following emergency PCS were 69%, 66%, 65%, 55%, and 51%, respectively, and following elective PCS were 95%, 90%, 70%, 65%, and 60%, respectively. Quality of life was similar in patients with and without PVT. Long-term PCS patency was demonstrated yearly in 93% of patients in the group with PVT and in 99.7% of patients without PVT. Other similarities after 5 years between patients with and without PVT, respectively, were the incidences of recurrent encephalopathy (9% vs. 8%), alcohol abstinence (61% vs. 64%), improved liver function (68% vs. 62% to 75%), and return to work (52% vs. 56% to 64%). It was concluded that in patients with cirrhosis and variceal hemorrhage it is almost always possible to remove portal vein thrombus by means of phlebothrombectomy and then perform a direct PCS with results similar to those achieved in the absence of PVT.
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PMID:Portal vein thrombosis in cirrhosis with variceal hemorrhage. 983 38

Plasma branched-chain amino acid (BCAA) levels are decreased in patients with liver cirrhosis, owing to an increase in BCAA tissue uptake and/or catabolism and a decrease in BCAA production from proteins. Non-specific factors such as malnutrition worsen this picture. Studies of BCAA fluxes and protein turnover in cirrhotic patients have given conflicting results due to patient heterogeneity, differences in method and bias in the expression of results. In well compensated cirrhosis, muscle wasting is moderate and probably due more to decreased protein synthesis than to increased protein catabolism. Hyperinsulinemia has been suggested as the main cause of decreased BCAA levels, by increasing BCAA uptake in muscle and additionally in adipose tissue. However, as depletion of fat stores is frequent in cirrhosis, this effect is certainly quantitatively weak. Also, there is no correlation between state of hyperinsulinemia and decrease in BCAA levels. An effect of cytokines (IL1 and TNF) on muscle BCAA catabolism is a possibility. Until recently, the contribution of the liver to abnormal BCAA metabolism has been underestimated. In cirrhotic liver an increase in liver transamination of branched-chain keto acids (BCKAs) has been suggested and may result from inhibition of liver BCKA dehydrogenase. A modification of protein turnover in cirrhotic liver must be also considered. Lastly, the contribution of non-hepatocyte liver cells, which are activated in cirrhosis, remains to be assessed.
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PMID:Abnormalities in branched-chain amino acid metabolism in cirrhosis: influence of hormonal and nutritional factors and directions for future research. 1045 77

In the past year, some relevant papers on the mechanisms of malnutrition in cirrhosis have been published. Studies investigating the metabolic destiny of leucine after protein breakdown, which have contributed to a better understanding of the pathogenesis of muscle wasting and fat depletion in these patients, deserve particular mention. Also, the demonstration that chronically reducing hyperinsulinaemia in cirrhosis is able to improve insulin sensitivity opens novel pathogenic and therapeutic perspectives for such a metabolic derangement in these patients. Other papers dealt with unsaturated lipids, lipoperoxidation and antioxidants in chronic liver disease. However, randomized trials on parenteral or enteral nutrition in cirrhosis and liver transplantation are missing.
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PMID:Nutritional issues in cirrhosis and liver transplantation. 1058 78

The prevalence of liver diseases is increasing in the United States, particularly as a result of the recent hepatitis C epidemic. In the past, patients who developed fulminant hepatic failure or cirrhosis owing to a chronic liver disease were likely to expire. During the last 15-20 years, liver transplantation has given these patients a chance at survival. Progressive nutrition deficiencies and muscle wasting are universal problems in these patients. Left untreated, the progressive wasting of liver disease leads to infection and an increased risk of death owing to infection both before and after transplantation. Aggressive nutritional support is essential to optimize the care of these patients and to enable them to obtain and survive a liver transplant and gain access to a new life following a successful liver engraftment.
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PMID:Nutrition support for individuals with liver failure. 1094 63

The cause of muscle wasting and decreased plasma levels of branched chain amino acids (BCAA), valine, leucine, and isoleucine in liver cirrhosis is obscure. Here we have evaluated the effect of hyperammonemia. Rats were infused with either an ammonium acetate/bicarbonate mixture, a sodium acetate/bicarbonate mixture, or saline for 320 minutes. The parameters of leucine and protein metabolism were evaluated in the whole body and in several tissues using a primed constant intravenous infusion of L-[1-14C]leucine. Ammonium infusion caused an increase in ammonia and glutamine levels in plasma, a decrease in BCAA and alanine in plasma and skeletal muscle, a significant decrease in whole-body proteolysis and protein synthesis, and an increase in leucine oxidized fraction. A significant decrease in protein synthesis after ammonium infusion was observed in skeletal muscle while a nonsignificant effect was observed in liver, gut, heart, spleen, and kidneys. We conclude that the decrease in plasma BCAA after ammonia infusion is associated with decreased proteolysis and increased leucine oxidized fraction.
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PMID:Effect of hyperammonemia on leucine and protein metabolism in rats. 1107 24


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