Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic function frequently becomes worse, after hepatectomy in patients with hepatocellular carcinoma associated with cirrhosis. We usually use insulin and glucagon to treat patients with poor hepatic function, so we examined hepatic function in these patients in relation to bile acid metabolism. 1) Total serum bile acid levels were increased in patients with cirrhosis, and serum GCDCA, TCDCA values were especially high. After surgery, they rose even higher. 2) Glucagon was shown to stimulate C-AMP and decreased total serum bile acid, and especially serum GCDCA and TCDCA values.
 ...
PMID:[Effect of glucagon on bile acid after hepatectomy in patients with hepatocellular carcinoma associated with cirrhosis]. 217 18

To study the consequences of hyperglycemia on glucose and nitrogen metabolism in cirrhosis, an hyperglycemic clamp was performed in 5 cirrhotic patients and 5 normal controls during two subsequent periods of 90 min, at 7.78 and then at 13.89 mmol/l. In the first period, glucose infusion and metabolic clearance rates were decreased in cirrhotics vs controls (p less than 0.05). In the second period, this difference between the two groups disappeared because of a more important enhancement in cirrhotics. Baseline plasma C peptide levels and those during hyperglycemia were the same during hyperglycemia in both groups, but plasma insulin level rose more in cirrhotics (p less than 0.05). Baseline insulin secretion following IV glucagon was reduced in cirrhotics vs controls (p less than 0.05), but became normal in the hyperglycemic state. Plasma glucagon levels were enhanced at all times in cirrhotics vs controls (p less than 0.01), but dropped more in cirrhotics vs controls (p less than 0.05). Insulin responsiveness, defined as the "glucose consumption: plasma insulin concentration" ratio was reduced in cirrhotics at 7.78 mmol/l (p less than 0.01), but was the same in both groups at 13.80 mmol/l because of a more important enhancement in cirrhotics, reflecting an improvement of insulin action probably at the post-receptor level and of non-insulin-mediated glucose transport. Hyperglycemia induced a drop in plasma concentration and muscular release of all aminoacids, excepted alanine, between the basal state and the end of the study. Aminoacid concentration rose only in cirrhotics, without any change in muscular output. In the same time, blood ammonia level rose only in cirrhotics, without reduction of muscular uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Consequences of hyperglycemia on glucose and nitrogen metabolism in liver cirrhosis. A study using a hyperglycemic clamp]. 219 90

The poor prognosis of severe acute alcoholic hepatitis has stimulated interest in specific forms of treatment aimed at reducing the short term mortality as well as preventing progression to cirrhosis. Several controlled trials of steroid therapy have suggested an improvement in short-term survival, but the benefit seems to apply to highly selected cases only. Treatment with propylthiouracil and insulin and glucagon infusions has also shown promising results in controlled studies but there is still no general agreement on their value. Despite recent interest in the use of colchicine to prevent progression of cirrhosis in chronic liver disease of other aetiologies, its role in alcoholic liver disease is not yet clear. In end-stage alcoholic cirrhosis, excellent results are now being achieved with liver transplantation, although this is limited to patients who are not alcohol dependent and in whom there is no alcohol-induced extrahepatic disease.
 ...
PMID:Treatment of advanced alcoholic liver disease. 187 84

To assess the metabolic characteristics of cirrhotic hepatocytes, a primary culture of hepatocytes was established using rat liver induced cirrhosis by CCl4 administration. Using this system, cell responsiveness to different metabolic and excretory stimuli was investigated and compared with a primary culture of normal healthy rat hepatocytes. Cirrhotic hepatocytes showed reduced protein synthesis in response to insulin and reduced urea synthesis in response to glucagon. However, DNA synthesis stimulated by insulin and EGF was significantly enhanced in cirrhotic hepatocytes. No significant difference was observed in the fluorescein diacetate excretion rate. Cirrhotic hepatocytes showed impairment of antipyrine metabolism and conjugation and excretion of unconjugated bilirubin. These results suggest indirectly that cirrhotic hepatocytes may be less functionally mature than normal healthy hepatocytes.
 ...
PMID:[Studies on metabolic characteristics of cirrhotic rat hepatocytes using primary culture]. 221 64

The contribution of obesity and/or diabetes to liver pathology in the morbidly obese patient is controversial. We studied the liver biopsies of 100 consecutive patients undergoing gastric bypass surgery for morbid obesity. Multiple morphologic parameters were analyzed and graded independently, without knowledge of the clinical history, liver function tests, and oral glucose tolerance results of the patients. Six percent of the entire group demonstrated no fat, 42% mild fat, 20% moderate fat, and 24% severe fatty metamorphosis of the liver. Twenty-three percent of the patients had central vein fibrosis, 23% sinusoidal fibrosis, 19% bridging fibrosis, and 4% cirrhosis. Thirty-six percent of the patients had some degree of steatohepatitis, 66% possessed so-called glycogen nuclei of hepatocytes, 6% had PAS-positive thickening of blood vessels in the portal tracts, and 1% had lipogranulomas. The degree of fatty metamorphosis and fibrosis was analyzed in three separate groups, categorized by the glycemic status of the patient: 46 patients with normal glucose tolerance (NGT), 23 patients with impaired glucose tolerance (IGT), and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM). Increasing severity of fatty metamorphosis from the normoglycemic obese to the diabetic obese patients was found, which was statistically significant by chi 2 analysis. Four of the six patients showing no fatty metamorphosis were normoglycemic. Glycogen nuclei and PAS-positive blood vessels were significantly more prevalent in the diabetic obese than in the normal obese. In conclusion, the distribution of significant liver histopathology in the morbidly obese patient correlates in severity with the degree of impaired glycemic status.
 ...
PMID:Liver pathology in morbidly obese patients with and without diabetes. 153 87

Alcoholic liver disease presents a wide spectrum of clinical manifestations ranging from mild asymptomatic fatty liver to alcoholic hepatitis and severe life-threatening liver failure with ascites, hemorrhaging esophageal varices, and encephalopathy. Although still poorly understood, the mechanism of this injury is probably the result of numerous direct toxic and metabolic effects of alcohol on the hepatocyte. Therapy consists primarily of abstinence and supportive care. However, several newer treatments are actively being studied. These include prednisolone, anabolic steroids, glucagon and insulin, propylthiouracil, and cyanidanol. Colchicine is promising as an agent to inhibit fibrosis. Complications of cirrhosis, including ascites and variceal hemorrhage, are the result of end stage disease. A return to old techniques of ascitic fluid management suggests that therapeutic large-volume paracentesis with albumin infusion is a safe and effective form of therapy. Variceal hemorrhage is best treated with sclerotherapy, vasoconstrictors, and balloon tamponade. Little has been done to alter the ultimately dismal prognosis and long-term survival of alcoholic liver disease.
 ...
PMID:Alcoholic liver disease. 222 93

Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma.
 ...
PMID:Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment. 222 85

Alcoholic hepatitis is a necrotizing, often inflammatory, process that is an important precursor to the development of cirrhosis. Acetaldehyde, which is derived from alcohol by the action of alcohol dehydrogenase, is apparently the most important factor leading to alcohol-induced liver injury. Other factors of importance in determining the appearance and rate of progression of liver diseases in patients who are chronic alcoholics include sex, nutritional status, and various immunologic reactions. In addition, there is an incompletely understood genetic predisposition to the development of alcoholic hepatitis. Several histologic features found in patients with alcoholic hepatitis have been evaluated in efforts to determine which are of prognostic value. The predominance of the alcohol-induced injury in zone III of the hepatic lobule; deposition of collagen, IgA, and fibronectin in the space of Disse; defenestration of endothelial cells; and transformation of lipocytes and myofibroblasts to fibroblasts have been investigated. Prolongation of the prothrombin time and marked elevation of serum bilirubin levels are indicators of a subgroup of patients with alcoholic hepatitis who have a poor prognosis, especially if there is also evidence of hepatic encephalopathy. Supportive care and abstinence from alcohol are the foundations of therapy. Corticosteroid therapy appears to decrease the number of early deaths in patients with severe alcoholic hepatitis. Other experimental approaches to therapy include the use of propylthiouracil, anabolic-androgenic steroids, and insulin and glucagon.
 ...
PMID:Alcoholic hepatitis: pathogenesis and approaches to treatment. 223 74

Mathematical models are a necessary tool to quantify physiological processes the direct measurement of which is not possible. Pancreatic beta-cell and liver are respectively the secreting and the major degrading site of insulin. To provide a quantitative description of these processes, we have conceived a method which exploits two minimal mathematical models. By using one model the post-hepatic delivery of insulin into the systemic circulation, IDRT(t), is estimated; the other model yields CPST(t), i.e. the secretion rate of C-peptide, which is equimolarly released by the beta-cell with insulin, but is not degraded by the liver. The estimated C-peptide flow rate into plasma is thus representative of that of pre-hepatic insulin. The difference between CPST(t) and IDRT(t) gives the insulin extraction by the hepatocytes. The parameters of the models are estimated in every single subject from the analysis of glucose, insulin, and C-peptide concentration data measured after an intravenous glucose injection. As an example of its usefulness, the method has been applied in patients with liver cirrhosis and in obese non-diabetic subjects, with the purpose of elucidating which mechanism is responsible for the peripheral dynamic hyperinsulinaemia characteristic of such metabolic states. Because mechanism is responsible for the peripheral dynamic hyperinsulinaemia characteristic of such metabolic states. Because of its relative non-invasiveness compared to other techniques this model-based method should prove useful in several other clinical investigations.
 ...
PMID:Estimation of beta-cell secretion and insulin hepatic extraction by the minimal modelling technique. 224 23

By examination of a group of 617 diabetics treated by oral antidiabetics (PAD) and 263 treated with insulin for HBs-antigen carriership (HBsAg) by counter immunoelectrophoresis (CIEP) a total of 34 HBsAg carriers were detected (3.84%). This number comprised 9 treated with PAD (1.5%) and 25 insulin-treated ones (9.5%). Only six were younger than 60 years, the remaining 28 were older. Comparison with results assembled in 1984 revealed that in both groups during the five-year interval a marked decline of the prevalence of carriership had occurred--in the PAD treated group from 4.9% to 1.5% and in the insulin treated group from 29.1% to 9.5%. The decline is above all due to the high mortality of diabetics who are HBsAg carriers. In the course of five years a total of 50% died. Formerly positive patients were, if CIEP was negative, examined also by the ELISA method. On examination by both methods 13 were negative (19.7%). Of the newly detected 14 carriers 7 suffered from cirrhosis of the liver, incl. five where examination of HBsAg revealed the disease. In eight patients the carriership was confirmed only by examination by the ELISA method. Of the latter five had previously alternately positive and negative results when examined by CIEP which indicates variations of the serum concentration of the antigen.
 ...
PMID:[Incidence of HBs-antigen in diabetics. III. Results of examination after 5 years]. 225 88


<< Previous 1 2 3 4 5 6 7 8 9 10