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)

Patients with cirrhosis show increased signal intensity in the globus pallidus on T1-weighted magnetic resonance imaging of the brain. This abnormal appearance of the basal ganglia has been related to the severity of liver failure and to the presence of portal-systemic shunting, although its cause and clinical significance remain unknown. We prospectively assessed the metabolic, neurological and neuropsychological statuses of 30 stable cirrhotic patients and correlated these clinical variables with computed measurements of globus pallidus signals. Some metabolic variables denoting disease severity appeared to be significantly related to image changes, although the strongest association was found with plasma ammonia levels. After adjustment for ammonia level, on multiple regression analysis, the other variables were not significant. Furthermore, pallidal changes were associated with specific neurological symptoms and neurological functions, symptoms and functions that also had a significant correlation with ammonia levels. Our findings suggest that globus pallidus signal abnormality could arise as a marker of brain impairment related to hyperammonemia.
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PMID:Pallidal hyperintensity on magnetic resonance imaging in cirrhotic patients: clinical correlations. 144 93

Zinc deficiency is common in cirrhosis and may be involved in the alteration of ammonia metabolism. Rats with carbon tetrachloride-induced cirrhosis have high plasma ammonia and low serum and tissue zinc levels. We used this model to examine the effects of oral zinc supplementation on activities of plasma ammonia and liver ornithine transcarbamylase (a key enzyme in the urea cycle). These parameters were examined in two consecutive experiments. Each experiment included two groups of rats treated with carbon tetrachloride; one group received zinc in the drinking water during the induction of cirrhosis, and another served as a control group. Regardless of zinc supplementation, all carbon tetrachloride-treated rats exhibited similar micronodular cirrhosis, with similar histological appearance and liver function impairment. Cirrhotic rats without zinc supplementation showed high plasma ammonia and low serum and hepatic zinc levels and reduced liver ornithine transcarbamylase activity. Serum, hepatic zinc and liver ornithine transcarbamylase activity increased significantly in the zinc-supplemented group, and these rats' plasma ammonia levels became normal. Plasma ammonia level was significantly inversely correlated with liver ornithine transcarbamylase activity and positively correlated with serum and hepatic zinc content. Our results suggest that zinc deficiency may modify hepatic ornithine transcarbamylase activity and, therefore, ammonia disposal.
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PMID:Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis. 150 22

A protein-free diet causes a paradoxical increase of blood ammonia levels that seems to be due to decreased liver content of acetylglutamate, the physiological activator of carbamylphosphate synthetase. The purpose of this study was to assess whether oral administration to rats of carbamylglutamate, a metabolically stable activator of carbamylphosphate synthetase, could decrease the blood ammonia levels increased by the protein-free diet. We show that ingestion of moderate doses of carbamylglutamate increased about sixfold the liver content of carbamylphosphate synthetase activators and restores to normal values the blood ammonia levels. Excess ammonia is eliminated in urine as urea. These results indicate that carbamylglutamate, which is not toxic, could be useful in the treatment of hyperammonemia, especially in cirrhosis.
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PMID:Treatment of hyperammonemia with carbamylglutamate in rats. 154 25

The work was designed to study the effects of a meat meal on glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma concentrations of glucagon, insulin, growth hormone, renin, aldosterone, total amino acids, and NH3 in healthy humans (H) as well as in patients with Child A liver cirrhosis (LC). The meat meal produced renal hyperaemia and hyperfiltration without changes in the filtration fraction. Fractional Na excretion in urine increased significantly after the meat meal only in LC. Hyperinsulinaemia and hyperglucagonaemia were seen at baseline in LC and were not affected by the meat meal, whereas in H glucagon concentration increased significantly over baseline within 30 min from the meat meal and insulin within 60 min. Growth hormone concentration was normal at baseline in LC and increased significantly 120-180 min after the meal, whereas it was not affected in H. Renin and aldosterone were stable in both H and LC. Plasma amino acid concentration began to increase 60 min after the meat meal, when hyperfiltration was present. The data indicate that in human Child A cirrhosis of the liver renal haemodynamic response to a meat meal is independent of changes in glucagon.
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PMID:Glucagon-independent renal hyperaemia and hyperfiltration after an oral protein load in Child A liver cirrhosis. 155 40

We report an unusual case of a large inferior mesenteric-caval shunt in a 25-year-old man without cirrhosis with hypoproteinemia and hypochromic anemia. In this large shunt the direct communication was between the inferior mesenteric vein and the internal iliac vein. Hemodynamic change as a result of the shunt was thought to cause his present clinical problems and future portosystemic encephalopathy. Percutaneous transcatheter embolization of the shunt with fibrin glue was performed through the internal iliac vein, and this offered amelioration of hypoproteinemia and reduction of serum ammonia levels without any complications. An interventional radiologic approach instead of surgical ligation should be attempted for portosystemic shunts, and fibrin glue, as well as coils or a detachable balloon, is also valuable as an embolizing material.
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PMID:Interventional embolization with fibrin glue for a large inferior mesenteric-caval shunt. 159 79

Ten children with advanced cirrhosis and malnutrition (less than 90% weight for height) were fed for eight weeks with a nasogastric feed comprising whey protein (enriched with branched chain amino acids), fat as 34% medium chain and 66% long chain triglycerides, and glucose polymer. Six of the children were studied for an eight week control period before feeding. Weight, triceps skinfold thickness, mid-arm circumference, mid-arm muscle area, and fasting plasma ammonia and amino acid concentrations were measured before and after the control period and after the consequent feed period. Results showed that despite high energy and protein intakes the children remained malnourished over the control period. All anthropometric indices improved significantly during the feed period, and no child developed clinical encephalopathy. The feed period was associated with a small, and not clinically significant, increase in the plasma ammonia concentration, but no consistent trend in the plasma amino acid concentrations. Thus, in children with advanced hepatobiliary disease awaiting liver transplantation, enteral feeding improved nutritional status without adverse clinical or biochemical effects.
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PMID:Intensive enteral feeding in advanced cirrhosis: reversal of malnutrition without precipitation of hepatic encephalopathy. 159 97

Despite a marked reduction of the urea cycle capacity, patients with well-compensated chronic liver disease excrete near-normal amounts of urea. Compensation of the urea cycle defect apparently occurs through the activation of liver glutaminase, as suggested by an inverse relationship between the in vitro ureagenic capacity and the flux through glutaminase in liver tissue from patients with a normal, fatty, or cirrhotic liver. In these patients, the flux through glutaminase, as determined in vitro, increases in parallel with the plasma bicarbonate level and plasma pH determined in vivo. In view of this and results from previous studies, the following hypothesis is suggested: The decrease of urea cycle enzyme activities in liver cirrhosis produces metabolic alkalosis due to an impaired bicarbonate elimination. Alkalosis in turn activates and stabilizes hepatic glutaminase and accordingly mitochondrial ammonia provision for carbamoylphosphate synthetase. This results in a compensatory stimulation of the urea cycle flux in the cirrhotic patient to near-normal rates, despite the marked reduction of urea cycle enzyme activity. Accordingly, alkalosis is an important driving force for urea synthesis in the cirrhotic patient. With respect to clinical medicine, attention must be paid to acid-base disturbances in the hyperammonemic patient.
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PMID:Metabolic alkalosis as driving force for urea synthesis in liver disease: pathogenetic model and therapeutic implications. 160 Mar 51

A prospective randomized double-blind study was conducted to evaluate the efficacy of sodium benzoate in the treatment of acute portal-systemic encephalopathy. Seventy-four consecutive patients with cirrhosis or surgical portasystemic anastomosis and hepatic encephalopathy of less than 7 days duration were randomized to receive lactulose (dose adjusted for 2 or 3 semiformed stools/day) or sodium benzoate (5 gm twice daily). Assessment of response included mental status, asterixis, arterial ammonia level, electroencephalogram and number-connection test. Each was given a score between 0 and 4+. A portal-systemic encephalopathy index was calculated with these scores. Visual, auditory and somatosensory evoked potentials and a battery of psychometric tests for intelligence and memory were also performed to assess improvement. Thirty-eight patients received sodium benzoate; 36 took lactulose. Thirty patients (80%) receiving sodium benzoate and 29 (81%) receiving lactulose recovered; the remaining patients died. Improvement in portal-systemic encephalopathy parameters occurred in both treatment groups and was similar (p greater than 0.1). Electroencephalogram and evoked potentials were not as helpful as mental status in assessing of recovery. Psychometric test scores remained abnormal after recovery of mental status (21 to 42 days) and were probably too sensitive for monitoring of these patients. The incidence of side effects was similar in the two treatment groups. The cost of lactulose for one course of therapy was 30 times that of sodium benzoate. We conclude that sodium benzoate is a safe and effective alternative to lactulose in the treatment of acute portasystemic encephalopathy.
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PMID:Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. 161 65

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

Urinary 15N-ammonia and 15N-urea were measured by gas chromatography-mass spectrometry after the intravenous administration of 15N-ammonia (0.2 mumol/kg/hr) to 6 volunteers and 11 patients with cirrhosis. Urinary 15N-nitrogen excretion as ammonia and urea was measured during the 210-min infusion period, and urea synthesis and ammonia conversion to amino acids were analyzed with a three-compartment model using the nonlinear least-squares method. The rate of urea synthesis in control subjects was 14.1 +/- 1.2 mg/kg/hr (mean +/- S.E.M.), and in cirrhotic patients it was 11.0 +/- 3.2 mg/kg/hr. The cirrhotic group was divided into those with compensated cirrhosis (Child class A patients) and those with decompensated cirrhosis (Child classes B and C patients), and the rates of urea synthesis for these groups were 14.5 +/- 1.5 and 8.9 +/- 1.6 mg/kg/hr, respectively. The difference between decompensated cirrhotic patients and control subjects was statistically significant (p less than 0.001). The percentage of ammonia reutilization of a given dose of 15N-ammonia was 75.9% +/- 2.4% in compensated cirrhotic patients and 82.9% +/- 3.6% in decompensated cirrhotic patients (p less than 0.05). Fasting venous ammonia levels correlated inversely with urea synthesis (p less than 0.001) and correlated positively with ammonia reutilization (p less than 0.05). These results are consistent with a decreased capacity to synthesize urea and an increased capacity to convert ammonia to amino acids in chronic liver failure.
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PMID:Metabolism of 15N-ammonia in patients with cirrhosis: a three-compartmental analysis. 163 43


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