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)

Morphological features of three models of portal-systemic encephalopathy in the rat were studied and compared with plasma ammonia levels and clinical observations. Carbon tetrachloride-induced cirrhosis with terminal coma produced a wide variety of structural changes in the brain whose severity was related to plasma ammonia levels at the time of death. These changes included diffuse gliosis, Alzheimer cells and focal neuronal necrosis but did not include spongiform changes in cerebral or cerebellar cortex. Porta-caval anastomosis (PCA) did not appear to produce any significant neurological symptoms. Rats with PCA of durations 1-30 weeks were studied and over this time the structural changes included astrocytic nuclear swelling, swelling of perivascular astrocytic foot-processes and spongiform change in the molecular layer of the cerebellum. No evidence of Alzheimer cells or gliosis was seen and plasma ammonia levels at no stage exceed twice the normal levels. Porta-caval anastomosis followed by gavage feeding with ammoniated cationic exchange resin produced severe neurological symptoms and marked hyperammonaemia. In these animals not only astrocytes but oligodendrocytes and neurons showed nuclear and cytoplasmic swelling and numerous Alzheimer type II cells were seen, together with a diffuse gliosis, but no evidence of spongiform change in the cerebral or cerebellar cortex was seen. It is concluded that ammonium ions are important in the genesis of morphological changes in the brain in rat models of portal-systemic encephalopathy, but the relevance of these changes to neurological dysfunction is uncertain.
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PMID:The brain in experimental portal-systemic encephalopathy. I. Morphological changes in three animal models. 687 6

Hepatic encephalopathy in patients with severe liver disease was associated with marked elevation of either serum methionine or blood ammonia levels or with simultaneous moderate increases in both parameters. CSF methionine levels also increased in encephalopathic patients with fulminant hepatitis and liver cirrhosis. Increased influx of methionine into the brain over the theoretical values predicted from Pardridge's equation suggested that accelerated transport of serum methionine across the blood-brain barrier was observed in these cases with hepatic encephalopathy. Hepatic encephalopathy in acute carbon tetrachloride liver injury could be obtained experimentally following intraperitoneal injection of ammonium acetate in rats, which already received intragastric administration of methionine. However, similar encephalopathy could not be observed by the administration of glycine or leucine in place of methionine. These results suggest at least that methionine and ammonia act synergistically on inducing hepatic encephalopathy.
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PMID:Impaired metabolism of methionine in severe liver diseases. II. Clinical and experimental studies on role of impaired methionine metabolism in pathogenesis of hepatic encephalopathy. 710 99

Thirty-one comatose patients (18 with cirrhosis of the liver, 13 with severe hepatitis) were treated with continuous haemofiltration on polyacrylonitrile membrane (AN 69). The mean duration of sessions was 45 +/- 37 h, during which 136 +/- 108 1 of ultrafiltrate were dialyzed. Sixteen patients emerged from coma, 14 (7 with cirrhosis, 7 with hepatitis) completely and 2 partially. Blood ammonium levels decreased by 47 +/- 21% during the first 24 hours. Aminoacid clearance ranged from 20 to 50 ml/min, but only non significant changes were observed in the branched-chain/aromatic aminoacid ratio. Provided the haemodynamic balance is preserved, the technique is well tolerated. The duration of dialysis depends upon the degree of thrombopenia induced. Since the long-term prognosis of both cirrhosis patients and severe hepatitis patients is unmodified, continuous haemofiltration can only be helpful in cases where hepatic regeneration is possible; failing this, liver transplantation should be considered.
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PMID:[Continuous haemofiltration in encephalopathy associated with hepatic failure (author's transl)]. 711 Sep 43

Hepatic encephalopathy in liver cirrhosis is due to several factors, including amino acid imbalance and hyperammonemia. Lactitol [correction of lactilol], a non adsorbable disaccharide, improves hepatic encephalopathy increasing bowel movements, modifying colonic bacteria and pH, and reducing blood ammonium. Ten patients with liver cirrhosis and longstanding stable hepatic encephalopathy were treated, after a period of drugs wash-out, with lactitol. A significant improvement of hepatic encephalopathy was observed, with a significant decrease of blood ammonium, related with the increase of stool frequency/day. Atrial natriuretic peptide decreased as well. Moreover, an increase of the ratio of plasma aliphatic amino acids (valine, leucine and isoleucine)/aromatic amino acid (tyrosine and phenylalanine) was observed. Lactitol is an effective drug in the treatment of chronic hepatic encephalopathy; its mechanism of action involves not only a decrease of blood ammonium but also modifications of the degree of plasma amino acid imbalance, and fluid and circulatory adjustments.
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PMID:Effects of lactitol [correction of lactilol] on hepatic encephalopathy and plasma amino-acid imbalance. 756 87

A course of hepamerz treatment (7 intravenous drip infusions followed by oral administration for 14 days) was tried in 14 patients with hepatic cirrhosis to clarify hepamerz effects on hepatic encephalopathy and hyperammonemia which were judged by blood ammonium levels and time of psychomotor tests. All the patients responded. Fasting ammonium levels reduced in 67%, after meal in 82% of patients, 68% improved their psychomotor parameters. Transient nausea as a side effect occurred in 3 patients.
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PMID:[The treatment of hepatic encephalopathy with Hepa-Mertz]. 766 79

Encephalopathy caused by hepatic cirrhosis is often associated with portasystemic shunt and hepatic parenchymal injury. Together, these are known as a combined-type symptom. Two experimental hepatic comatose models with combined-type symptom were developed in rats. Both of these models involve the administration of ammonium acetate (500 mg/kg) into the cecum in portacaval shunted (PCS) rats. In addition, hepatic injury was induced in one model by carbontetrachloride (CCl4) and in the other by dimethylnitrosamine (DMNA). These model rats showed a higher increase in the concentration of ammonia in the blood and a higher incidence of coma as determined by the loss of the righting reflex than did rats subjected to a shunt only (PCS operation + ammonia loading) or hepatic parenchymal injury only (CCl4 treatment + ammonia loading). The effect of lactitol, administered orally for 7.5 days, on the experimental hepatic coma was compared with that of lactulose. Lactitol significantly inhibited the increase in blood and brain ammonia concentration at doses of 3 and 6 g/kg/day and also reduced the incidence of coma. The effects of lactitol were similar to those of lactulose, a therapeutic agent for hepatic encephalopathy. Therefore, lactitol should be useful in the clinical treatment of hyperammonemia or hepatic encephalopathy.
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PMID:[Effect of lactitol (NS-4) on the increase in blood and brain ammonia concentration and on coma in newly developed rat models of hepatic coma]. 773 97

In an attempt to design a liver function test which takes into account both portal-systemic shunting and hepatocellular dysfunction, we investigated a group of patients with cirrhosis with or without surgical porta-caval shunt for d-propoxyphene and its major metabolite, norpropoxyphene kinetics. A small dose of d-propoxyphene (0.7 mg/kg body weight) was given orally to seven normal subjects, 15 patients with cirrhosis and seven patients with cirrhosis and surgical portacaval shunt. D-propoxyphene and norpropoxyphene areas under the plasma concentration-time from 0 to 4-h (AUC) were determined by the trapezoidal method. As d-propoxyphene is a high extraction drug and since the production of norpropoxyphene should reflect the amount of d-propoxyphene available to the hepatocytes, we tested the hypothesis that norpropoxyphene/d-propoxyphene AUC ratios should reflect both the degree of portal-systemic shunting and the severity of hepatocyte dysfunction. Norpropoxyphene/d-propoxyphene AUC ratios were significantly lower in patients with cirrhosis (mean +/- S.D.: 0.92 +/- 0.59) than in controls (2.51 +/- 0.45) and also significantly lower in patients with cirrhosis and a surgical shunt (0.53 +/- 0.23) than in patients with cirrhosis but without surgical shunt (1.10 +/- 0.63). Moreover, there was an overall statistically significant correlation between norpropoxyphene/d-propoxyphene AUC ratios and branched to aromatic amino acids ratios (rs = 0.91) and fasting venous NH4 (rs = -0.63). On the other hand, there was only a weak correlation between norpropoxyphene/d-propoxyphene AUC ratios and the 14C-aminopyrine breath test (rs = 0.43). These data suggest that the norpropoxyphene/d-propoxyphene AUC ratio reflects both shunting and reduced hepatocellular function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:D-propoxyphene and norpropoxyphene kinetics after the oral administration of D-propoxyphene: a new approach to liver function? 783 95

The case of a 58-year old woman with cirrhosis complicated by hepatocellular carcinoma, hepatic encephalopathy and superior mesenteric varices is described. Angiography revealed large superior mesenteric varices and it was demonstrated that the portal venous blood was shunted into the right internal iliac vein via the right ovarian vein. Clinically, this patient had hepatic encephalopathy and hyperammonaemia, but no oesophageal varices were discovered on endoscopy. The hepatic encephalopathy suggested that the portal blood containing ammonium from the superior mesenteric vein entered the brain through the systemic vein without the ammonia being metabolized by the liver.
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PMID:Superior mesenteric varices and splenic renal shunt with portal hypertension: a case report of liver cirrhosis with complications. 839 86

We present a case of portal-systemic encephalopathy due to a congenital splenorenal shunt. A 69 year old woman was admitted to hospital because of recurrent episodes of disturbed consciousness. The present episode had begun 3 months prior to admission. Although the patient demonstrated mildly slurred speech, the remainder of her neurological examination was unremarkable. She showed no clinical signs of portal hypertension and her liver function, except for a serum hepaplastin test of 58% and an ICG retention rate of 28% at 15 min, was normal. Her serum ammonium level was 210 micrograms/dL. The venous phase of a superior mesenteric arteriogram revealed a splenorenal shunt and narrowing of the portal vein, which was 4 mm in diameter. The histological findings, demonstrated by a needle liver biopsy specimen, were consistent with mild fibrosis and lymphocytic infiltration. Following the diagnosis of a splenorenal shunt in the absence of liver cirrhosis, ligature of the shunt was performed with a splenectomy. The portal vein pressure after ligature of the shunt rose from 12.5 to 18.8 mmHg. This shunt was thought to be of congenital origin. The high preoperative serum ammonia concentration decreased to the normal range postoperatively and the serum hepaplastin test and ICG retention rate similarly improved postoperatively. A follow-up superior mesenteric arteriogram was performed during the venous phase, demonstrating resolution of the shunt and decreased portal vein narrowing. The patient has suffered no further episodes of disturbed consciousness postoperatively.
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PMID:Case report: portal-systemic encephalopathy due to a congenital extrahepatic portosystemic shunt. 919 90

Hepatocyte growth factor (HGF), identified in ultrafiltered ascites and plasma from patients with cirrhosis, enhances the DNA synthesis in adult rat hepatocytes cultured at low cell density. This study was carried out to investigate the effect of ascites and plasma from patients with cirrhosis on liver-specific functions such as albumin synthesis in adult rat hepatocytes cultured at confluent-cell density. Ultrafiltered ascites from patients with cirrhosis and its ascitic protein, partially purified by fractionation with ammonium sulfate and gel filtration on Sephadex G-200, stimulated albumin synthesis in a dose-dependent manner in the presence of 10(-8), M dexamethasone. This effect was greater than that of 10(-7) M insulin and similar to that of 10(-7) M dexamethasone, but was additive with that of insulin plus dexamethasone. The molecular weight of the ascitic factor was estimated as 100,000 to 150,000, corresponding to that of HGF purified from cirrhotic ascites. Moreover, the partially purified ascitic factor markedly stimulated DNA and protein synthesis in hepatocytes. These findings suggest that the ascitic factor may act as HGF by stimulating hepatocyte DNA and albumin synthesis in a cell density-dependent manner.
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PMID:Stimulation of albumin synthesis in rat hepatocytes by ascites from patients with cirrhosis. 910 Apr 64


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