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Biomedical subjects

R Poupon

Publications and source records attributed to R Poupon.

At least 181 records · Page 10Linked to original sources

[Hepatic involvement associated with ingestion of metapramine].

The authors report the cases of 3 women who developed hepatic injury during administration of metapramine, a tricyclic antidepressant introduced in France in 1984. One patient had jaundice and pruritus; the 2 others had loss of weight. Serum alkaline phosphatase and serum transaminase activities were increased in 3 and 2 patients, respectively. Blood hypereosinophilia was found in one patient; erythrocyte sedimentation rate was elevated in 2 patients. The outcome was favorable after drug withdrawal in the 3 patients. Liver biopsy showed centrolobular cholestasis in the 3 patients. There was no rechallenge; in 2 patients, other drugs than metapramine might be implicated in hepatic injury; however, the similarity of these 3 cases suggests that metapramine, like other tricyclic antidepressants, may be responsible for hepatic injury.

Aged↗

Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis?

The effects of ursodeoxycholic acid (UDCA, 13-15 mg/kg body weight daily) were prospectively evaluated in fifteen patients with primary biliary cirrhosis (PBC). The mean concentration of UDCA in serum expressed as the percentage of total bile acids rose from 0% at baseline to 58% (SEM 9%) after 2 years' treatment, whereas total serum bile acid levels did not change significantly. The proportion of patients with pruritus necessitating the use of cholestyramine was significantly lower at 2 years than at baseline. Standard liver function tests improved in all the patients. At 2 years the average activities of gamma-glutamyltranspeptidase, alkaline phosphatases, and alanine aminotransferase and bilirubin levels were reduced (respectively 78%, 65%, 68%, and 36% of pretreatment values). In three patients who agreed to interrupt the ingestion of UDCA for 3 months after 2 years' treatment there was clear deterioration in liver function tests, which again improved after reinstitution of UDCA. These results suggest that long-term UDCA might be a safe and effective treatment for PBC, but a randomised, controlled, double-blind trial is urgently needed.

Adult↗

Hepatic extraction, metabolism and biliary excretion of doxorubicin in the isolated perfused rat liver.

The hepatic extraction, metabolism, and biliary excretion of doxorubicin (DX) were studied in the isolated perfused rat liver. Three doses of DX equivalent to 2, 20, and 100 mg/kg in rats were studied over a period of 3 h after bolus injection into the reservoir. DX and metabolites concentration in perfusate, bile, and liver were determined by high-pressure liquid chromatography. The hepatic extraction ratio was low (less than 0.24) and decreased progressively over the 3 h. The hepatic extraction and clearance were significantly lower at the highest dose. Doxorubicinol (DX-OL) was the only metabolite detected in the perfusate, accounting for less than 4% of the total AUC. Thirty-one to thirty-three percent of the dose was excreted into bile over 3 h as unchanged DX. This was reduced to 22% at the highest dose. Only 0.35%-1.33% of the dose was excreted as DX-OL. DX aglycones were found only in the liver, where they represented 20%-30% of the total fluorescence at 3 h. In conclusion, in this model DX has a low extraction ratio, is poorly metabolized and extensively excreted into bile.

Animals↗

Intractable ascites in systemic mastocytosis treated by portal diversion.

A 50-year-old male presented with intractable ascites due to systemic mastocytosis. The diagnosis of systemic mastocytosis was established by histology of the bone marrow which showed mast cell infiltration and fibrosis. Ascites was related to portal hypertension which was documented by esophageal varices at endoscopy and by an increase of wedged-free hepatic venous pressure gradient. Liver biopsy disclosed dense fibrosis of hepatic arterial and portal venule walls, resulting in complete obstruction of some portal radicles. Peliosis hepatis and fibrous deposits in the walls of hepatic venules were also present. Because of intractable ascites and significant malnutrition, a portacaval shunt was performed which cleared ascites and dramatically improved the general condition of the patient.

Ascites↗

Liver adenoma and focal nodular hyperplasia in a man with high endogenous sex steroids.

The authors report the case of a 29-yr-old man presenting with both hepatocellular adenoma and focal nodular hyperplasia. The patient had never been treated with androgens or estrogens. Investigations revealed the existence of high plasma levels of androgens and estrogens. In addition, the patient presented features compatible with the syndrome of partial androgen resistance. We propose that the hepatic lesions could be secondary to an abnormally high secretion of sex steroids. We suggest that in the absence of known intake of either estrogens or androgens, the existence of hepatocellular adenoma or focal nodular hyperplasia, or both, should indicate a search for abnormal secretion of sex steroids.

Adult↗

Hepatic uptake of sex steroids in men with alcoholic cirrhosis.

We attempted to determine to what extent the degree of liver function impairment might affect the hepatic uptake and, as a consequence, alter the systemic plasma levels of endogenous sex steroids in male patients with alcoholic cirrhosis. The plasma levels and hepatic uptake of the steroids dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, progesterone, and 17-hydroxyprogesterone were assessed. Systemic plasma levels of testosterone and dehydroepiandrosterone were significantly (p less than 0.05) reduced, whereas those of androstenedione, estrone, and estradiol were significantly (p less than 0.05) elevated in men with alcoholic cirrhosis when compared to controls. Sex hormone binding globulin levels were also significantly elevated (p less than 0.01). The hepatic uptake of sex steroids depended on the degree of liver function impairment as shown by the linear significant relationship between their hepatic extractions and that of indocyanine green (r = 0.74-0.92, p less than 0.05; except for dihydrotestosterone, r = 0.17, not significant). In addition, the hepatic uptake of sex steroids depended on the binding affinity to sex hormone binding globulin. The higher the affinity for sex hormone binding globulin, the lower the hepatic uptake influenced by liver function impairment. It was estimated that hepatic clearances accounted for only 20%-50% of the metabolic clearance of sex steroids. No significant relationship between plasma levels of sex steroids and their hepatic clearance was found. We show here that in alcoholic cirrhosis the extent of hepatic uptake of sex steroids depends partly on the degree of liver function impairment and partly on the degree to which they are bound to sex hormone binding globulin. Production rate or peripheral metabolism, or both, rather than hepatic uptake alone may account for the altered circulating levels of sex steroids.

Adult↗

[Does the size of esophageal varices have a prognostic significance in alcoholic cirrhosis?].

This study was designed to determine whether the size of esophageal varices were of prognostic value in patients with alcoholic cirrhosis. Esophageal varices were classified into 2 groups according to whether their size was larger or smaller than 4 mm. There was a total of 99 patients; 56 had small varices and 43 had large varices. Of the clinical and biological data collected at the time of determination of the size of the esophageal varices, only the duration of cirrhosis and the prevalence of gastrointestinal bleeding were significantly greater in patients with large esophageal varices. The one- and two-year cumulative rates of patients with large esophageal varices were 63 +/- 7 p. 100 and 42 +/- 8 p. 100, respectively; these results were not significantly different from those in patients with small esophageal varices, i.e. 68 +/- 6 p. 100 and 61 p. 100 respectively (p less than 0.5 for one-year survival; p less than 0.08 for two-year survival). Serum bilirubin and albumin as well as the presence of ascite were of significant prognostic value concerning death at two years while the presence of esophageal varices did not significantly increase the prognostic value of the above-mentioned variables (using Cox's regression model). In conclusion, the results of our study suggest that large esophageal varices, in spite of their association with a high incidence of gastrointestinal bleeding, do not influence prognosis at two years for patients with alcoholic liver cirrhosis.

Esophageal and Gastric Varices↗

Norepinephrine: a potential modulator of the hepatic transport of taurocholate. a study in the isolated perfused rat liver.

The effects of norepinephrine on portal blood flow hepatic extraction and intrinsic clearance of taurocholate were studied in the isolated perfused rat liver. Livers were perfused at a constant pressure. [14C]Taurocholate was infused continuously at a rate of 0.6 mumol/min. Then, three increasing doses of norepinephrine were added to the perfusate. Norepinephrine induced a significant dose-dependent reduction in portal blood flow. In spite of this reduction, taurocholate extraction did not increase and intrinsic clearance decreased significantly. When portal blood flow was decreased mechanically, intrinsic clearance was, as expected, flow-independent. The effects of norepinephrine on portal blood flow and intrinsic clearance were antagonised by phentolamine but not by propanolol. Norepinephrine decreases independently both portal blood flow and the vectorial transport of taurocholate. These effects are mediated by alpha adrenergic receptors.

Animals↗

Expression of blood group antigens including HLA markers in human adult liver.

The localisation of the principal blood group antigens has been studied in human liver. These blood group antigens included the erythrocyte antigens and the antigen of the major histocompatibility complex. This study was performed by the indirect immunofluorescence technique using polyclonal antibodies of human or animal origin and monoclonal antibodies from hybridomas. This study has shown that the normal hepatocyte is lacking in blood group antigens. On the contrary, the biliary cell was rich in antigenic markers: the main antigens expressed were Lewis, Pr, HLA-A and B antigens. In Kupffer cells, only i and HLA-DR antigens were clearly expressed. The endothelial cells of blood vessels mainly show A, B, H, HLA-A and B antigens; HLA-DR and Pr are slightly expressed. HLA-DR antigens were more strongly expressed on veins than on arteries. Dendritic cells have been identified in the portal space of human liver. They bore i and HLA-DR antigens.

ABO Blood-Group System↗

[Association of autoimmune chronic active hepatitis and acquired erythroblastopenia cured by cyclophosphamide].

To the best of our knowledge this is the reported first case of the successive occurrence in the same patient of chronic active hepatitis and acquired pure red cell aplasia, both probably of autoimmune origin. The diagnosis of autoimmune hepatitis was based on the presence of characteristic lesions at the examination of the liver biopsy specimen, high titer of anti-smooth muscle antibodies in the serum, and remission obtained by steroid therapy. Erythroid aplasia, which appeared during the course of this treatment, was revealed by a regenerative anemia (4.4 g Hb/100 ml) and proved by bone marrow aspiration and biopsy. In vitro bone marrow culture was normal, suggesting the in vivo presence of an inhibitor of erythroblastic differentiation. Red cell aplasia was cured by cyclophosphamide (100 mg/day during 56 days). No recurrence was noted until the death of the patient, which occurred one year later, due to hepatic cholangiocarcinoma. Action of cyclophosphamide on the pure red cell aplasia suggested the immune origin of this disease. The liver and the bone marrow erythroid lineage have probably been the successive targets of immunologic dyscrasia.

Autoimmune Diseases↗

[Nodular regenerative hyperplasia of the liver and primary biliary cirrhosis. A fortuitous association?].

We report here in a case of primary biliary cirrhosis associated with nodular regenerative hyperplasia of the liver in a white woman revealed by digestive hemorrhage due to ruptured esophageal varices. The diagnosis of primary biliary cirrhosis was based on the following: elevated serum IgM, high titer of antimitochondrial antibody (anti M2), typical histopathological picture of stage I/II disease. The diagnosis of nodular regenerative hyperplasia was supported by the demonstration of disseminated small hepatic nodules without perinodular fibrosis. This association may be a supplementary argument in favor of a possible autoimmune origin of nodular regenerative hyperplasia of the liver.

Aged↗

[Ascites disclosing systemic lupus erythematosus].

We report the case of a 38-year old woman with massive ascites. No cause could be demonstrated despite multiple investigations. The patient was febrile and had an elevated erythrocyte sedimentation rate. Systemic lupus erythematosus was subsequently diagnosed, when malar rash, arthritis, leucopenia, anti-native DNA and anti-Sm antibodies appeared. Ascites and lupus manifestations resolved simultaneously on steroid therapy. This unusual cause of ascites should be recognized, since it responds favorably to steroid therapy.

Adult↗