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Biomedical subjects

S Erlinger

Publications and source records attributed to S Erlinger.

At least 73 records · Page 4Linked to original sources
PubMed1996

Restriction of V beta gene usage of liver-derived lymphocytes in chronic hepatitis B and C.

T lymphocytes have been reported to be the predominant inflammatory cells in the liver of patients with chronic viral hepatitis. Their presence may reflect either nonspecific inflammation or a virus-specific immune response. To assess the repertoire of intra-hepatic T cells, we investigated the TCR V beta gene usage of T cells in 10 patients with chronic hepatitis B and 15 with chronic hepatitis C. Liver-derived lymphocytes and peripheral blood lymphocytes were analyzed by flow cytometry. Five out of the 10 hepatitis B patients were found to have an accumulation of certain V beta T cells in the liver (V beta 6.7; V beta 6.7; V beta 3.1, V beta 5.1, and V beta 6.7; V beta 3.1; V beta 12.1, respectively). Four out of the 15 hepatitis C patients were found to have an accumulation of certain V beta T cells in the liver (V beta 5.1; V beta 8 and V beta 5.2 and 5.3; V beta 3.1 and V beta 5.2 and 5.3; V beta 3.1 and V beta 12.1, respectively). Despite a limited screening of V beta subfamilies, this study indicates that, in patients with chronic hepatitis B and C, T cells using a certain V beta gene may accumulate in the liver. This suggests that intra-hepatic T cells are oligoclonal and possibly virus specific. Our results argue against the role of a superantigen in perpetuating liver disease. In addition, this study supports a role for T lymphocytes in the pathogenesis of chronic hepatitis C.

Adult↗
PubMed1996

Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. French Group of Clinicians and a Group of Biologists.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunts reduce portal pressure and can control ascites in patients with cirrhosis. We carried out a controlled study to evaluate this procedure for the management of refractory ascites in patients with cirrhosis and to clarify its mechanism of action. METHODS: Twenty-five patients with refractory ascites were included in the trial; 13 were randomly assigned to shunts and 12 to paracentesis. Four patients in each group were Child-Pugh class C and the others were class B. Follow-up ranged from 9 to 34 months. Hemodynamic values, liver and renal tests and neurohumoral factors were measured before and at 4 months after inclusion. RESULTS: Shunts were successfully placed in 10 out of 13 patients. At 4 months, ascites had improved in all class B patients in the shunt group and in none of the patients in the paracentesis group (p < 0.05); ascites did not improve in any of the class C patients in either of the groups. At 2 years, the overall survival rate was 29 +/- 13% (mean +/- SE) in the shunt group and 56 +/- 17% in the paracentesis group (p < 0.05). In class B patients, there was no significant difference in mortality. At 4 months, portal pressure was significantly lower than before the shunt, while plasma levels of atrial natriuretic peptide were significantly higher and plasma levels of renin and norepinephrine significantly lower. CONCLUSIONS: In this trial, intrahepatic shunts were effective on refractory ascites in patients with cirrhosis. However, the overall survival rate was lower in shunted patients than in those treated with paracentesis. The efficacy of intrahepatic shunts on ascites was only observed in class B patients. Survival did not improve in class B patients, and decreased in class C patients compared to paracentesis. The efficacy of shunts on ascites might be due to neurohumoral factors which control natriuresis and depend on hepatic sinusoidal pressure.

Ascites↗
PubMed1996

Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone.

BACKGROUND & AIMS: Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis. However, independent factors associated with a favorable outcome and long-term survival are unknown. The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis. METHODS: Of 183 patients studied, 61 had been randomized in a previous trial; 32 of them were treated with prednisolone (group I) and 29 were not treated (group II); 61 were treated from the end of this randomized trial (group III); and 61 were simulated (group IV). RESULTS: At 1 year, survival in group I (69%; confidence interval [CI], 57%-81%) and group III (71%; CI, 55%-87%) was better than in the nontreated groups (group II, 41%; CI, 23%-59%; P = 0.01) (group IV, 50%; CI, 37%-63%; P = 0.05). At 2 years, survival was not significantly different. Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival (76%; CI, 64%-88%) than the others (53%; CI, 35%-71%; P = 0.05). Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival (77%; CI, 65%-89%) than the others (40%; CI, 14%-66%; P = 0.003). In the 93 treated patients, liver polymorphonuclear infiltrate (P < 0.03) and polymorphonuclear count (P < 0.001) were independently correlated with 1-year survival. CONCLUSIONS: Prednisolone reduced mortality by at least 1 year. Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors.

Female↗
PubMed1996

Retrograde injections of formaldehyde into the biliary tree induce alterations of biliary epithelial function in rats.

Formaldehyde may induce severe lesions of intrahepatic and extrahepatic bile ducts. The purpose of this study was to examine in vivo the functional consequences of an alteration of the biliary epithelium induced by a retrograde intrabiliary injection of formaldehyde in rats. After basal bile collection, a 10% formaldehyde solution was injected into the biliary tree of anesthetized rats, and the cannula was occluded for 30 minutes. Choleresis was then reestablished, and bile flow, bile acid, and bicarbonate secretion were measured both spontaneously and during ursodeoxycholate infusions. Formaldehyde injections induced a significant increase in bile flow and a marked inhibition of ursodeoxycholate-induced increase in biliary bicarbonate concentration and secretion. Biliary glucose secretion, which is normally very low, was increased about 20-fold in animals injected with formaldehyde. Histological and ultrastructural examination of the liver showed alterations of biliary epithelial cells, whereas hepatocytes, bile canaliculi, and canalicular tight junctions remained normal. Hepatocytic excretory function, as assessed by biliary secretion of bile acids, was not affected. It was concluded that short-term formaldehyde intrabiliary injections cause an inhibition of ursodeoxycholate-induced hypersecretion of bicarbonate, an increase in biliary glucose secretion, and selective structural alterations of biliary epithelial cells. These results suggest that formaldehyde retrograde biliary injection may be a useful model to study alterations of biliary epithelial function in vivo.

Animals↗
PubMed1996

Relationship between composition of lymphoid cell infiltrates in the liver and replication status in chronic hepatitis B: an immunohistochemical study.

The purpose of this in situ immunophenotyping study was to assess the nature of lymphoid cells involved in chronic hepatitis B with various levels of replication. Replicative status was studied in 25 patients with chronic hepatitis B. Different subsets of T cells, B cells, natural killer cells, and follicular dendritic cells were counted with a computerized image analyzer. Twelve patients had chronic hepatitis B with a high level of replication, nine without replication, and four with a low level of replication. The number of CD3+ T cells was significantly higher in the liver of patients with replication. In all cases, CD8+ T cells were the most numerous cells in the lobules and CD4+ T cells were the most numerous cells in the portal tract. Intra-portal lymphoid follicles were observed in 33% of patients with a high level of replication. The CD57+ natural killer cells were more numerous in patients with a low level of replication. This study suggests that in immunocompetent patients, the intensity and type of hepatic immune response are directly determined by the HBV replication.

Adult↗
PubMed1996

Review article: new insights into the mechanisms of hepatic transport and bile secretion.

The transport processes responsible for bile flow are reviewed. Canalicular bile acid-dependent flow is the result of active transport of bile acids by the hepatocyte into bile canaliculi. Bile acids are taken up by at least two transport systems whose mRNA have been expressed in Xenopus oocytes: (i) a Na(+)-dependent system, named NTCP, and (ii) a Na(+)- independent system, named OATP. Bile acids are then secreted into bile by two other transport systems, an ATP-dependent system and an 'electrogenic' voltage-dependent system. It is not known whether these two systems are mediated by the same protein or by two different proteins. Canalicular bile acid-independent flow is mainly the result of the secretion of glutathione into bile. The canalicular membrane also contains several proteins of the multi drug resistance (MDR) family. MDRI is responsible for biliary secretion of cationic drugs. MDR3 (mdr 2 in mice) plays a major role in the secretion of phospholipids. A third MDR-related protein has been shown recently to be the canalicular carrier of organic anions, such as bilirubin and dyes (the canalicular multiple organic anion transporter, or cMOAT). Biliary epithelial cells secrete a bicarbonate-rich solution, mostly in response to secretin. This secretion depends upon the presence, on the apical membrane of these cells of the CFTR, a chloride channel activated by cAMP and of a chloride/bicarbonate exchanger. Knowledge of these transport systems should allow a better understanding of the mechanisms involved in cholestasis.

Animals↗
PubMed1996

Effect of diethylmaleate on bile secretion and ultrastructural appearance of hepatocytes in normal rats and mutant rats with defective organic anion secretion.

Diethylmaleate is an organic anion secreted into bile as a glutathione conjugate. Its transport by the hepatocyte is associated with dilatation of the Golgi apparatus and the appearance of small vesicles in the pericanalicular area. It has been speculated that the Golgi apparatus could play a role in the intracellular transport and/or the biliary canalicular secretion of diethylmaleate. The purpose of this work was to determine whether the alterations in the Golgi apparatus and the pericanalicular vesicles could mediate the canalicular secretion of diethylmaleate. Diethylmaleate biliary secretion and diethylmaleate-induced bile flow were measured in Sprague-Dawley rats, and in TR- rats which have an inherited defect in the excretion into bile of organic anions, including glutathione conjugates. Livers of both Sprague-Dawley and TR-rats were examined by electron microscopy, to characterize the changes in intracellular organelles. In Sprague-Dawley rats, as previously described, diethylmaleate administration was associated with an increase in bile flow, which was parallel in time to the secretion into bile of diethylmaleate conjugates. Electron microscopic examination of the liver after diethylmaleate administration showed dilatation of the Golgi saccules. In contrast, in TR- rats, the increase in bile flow and the secretion of diethylmaleate conjugated were nearly absent. Nevertheless, electron microscopic examination showed a dilatation of the Golgi saccules similar to that observed in Sprague-Dawley rats. TR- rats, in addition to the changes in the Golgi apparatus, had marked dilatation of the endoplasmic reticulum. These results show that biliary secretion of diethylmaleate conjugates was severely impaired in TR- rats, in spite of a dilatation of the Golgi apparatus and of the endoplasmic reticulum. We conclude that it is unlikely that the alterations in the Golgi apparatus (and the endoplasmic reticulum) induced by diethylmaleate play a role in the canalicular secretion of diethylmaleate. We do not exclude the possibility that these organelles could play a role in intracellular transport of this compound. Alternatively, these alterations could be due to a "toxic" effect of diethylmaleate accumulation in hepatocytes.

Animals↗
PubMed1996

Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography.

The aim of this study was to prospectively evaluate endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis not detected by conventional ultrasonography. Forty five consecutive patients (26 females, 19 males, mean age: 50 years) with suspected cholecystolithiasis and at least two normal transcutaneous ultrasonography examinations were included. Endoscopic ultrasonographic criteria for the diagnosis of cholecystolithiasis were the presence of stones with or without acoustic shadowing or sludge. Criteria of microscopic examination of bile were cholesterol or bilirubinate crystals or spheroliths. Thirty three patients underwent cholecystectomy and lithiasis was found in gall bladder bile in 24. Twelve patients who were not operated on and were followed up (median: 17 months), had no evidence of cholecystolithiasis. Endoscopic ultrasonography and duodenal bile examination were 96% and 67% sensitive, respectively (p < 0.03). The specificity was not different (86 and 91%, respectively). None of the 16 patients with negative results in both procedures had evidence of cholecystolithiasis. It was found that for the diagnosis of cholecystolithiasis in patients with normal conventional ultrasonography, the sensitivity of endoscopic ultrasonography is higher than that of microscopic examination of duodenal bile. If endoscopic ultrasonography and microscopic examination of duodenal bile are negative, the risk of underdiagnosing cholecystolithiasis is negligible.

Adult↗
PubMed1996

Do intracellular organelles have any role in transport of bile acids by hepatocytes?

The mechanisms of intracellular transport of bile acids by the hepatocyte and the regulation of their canalicular secretion are still incompletely understood. In this article, the evidence for a role of intracellular vesicles in bile acid transport by the hepatocyte is reviewed. Electron microscopic, immunoperoxidase, immunofluorescent and autoradiographic observations have shown a localization of bile acids on intracellular vesicles, on the Golgi apparatus and endoplasmic reticulum. Microtubule inhibitors, such as colchicine and vinblastine, have been shown to inhibit bile acid transport into bile. These observations are consistent with the hypothesis that bile acid canalicular transporters are recycled from an intracellular vesicular pool to the canalicular membrane. This membrane trafficking is a microtubule-dependent process. Confirmation of this hypothesis will require direct demonstration of the transporters on intracellular vesicles and movement of these vesicles to the canalicular membrane under appropriate conditions.

Animals↗
PubMed1996

[Natural history of dysthyroidism during interferon treatment of chronic hepatitis C].

Thyroid dysfunction developed in 35 patients among a series of 300 (190 men and 110 women) treated with alpha-interferon (35/300 = 12%. No relationship was observed between the type of alpha-interferon, the dose, or hepatic response, but there were more women (24/35). Antithyroid antibody levels were frequently elevated before treatment (8/35, 23%). Hypothyroidism developed in 27 patients, 7 with clinical hypothyroidism, 10 with moderate hypothyroidism and 5 with elevated TSH only. Patients with severe symptoms and highly elevated thyroid antibodies were more prone to develop sustained or irreversible hypothyroidism (10 patients). Twelve patients recovered a normal thyroid function within a few months, but antibody levels fell more slowly. Primary hyperthyroidism of variable severity appeared in 13 patients. In 8 patients, normal thyroid function was recovered within a few weeks but thyroid antibodies remained high for at least one year. In 5 others spontaneous hypothyroidism occurred within a few weeks ("biphasic" hypothyroidism). Direct toxicity appears to be less probable than an autoimmune mechanism; elevated antithyroid antibodies were observed in only 20 patients (57%). In clinical practice, TSH levels should be regularly monitored during and after alpha-interferon therapy.

Adult↗
PubMed1995

Transplantation for fulminant and subfulminant hepatic failure with preservation of portal and caval flow.

This article describes experience with preservation of portal and caval flow during orthotopic liver transplantation (OLT) for fulminant or subfulminant hepatic failure (FSHF) as an alternative to venous bypass. As a modification of the standard procedure, hepatectomy and graft implantation were performed with preservation of caval patency in combination with a temporary portocaval shunt. From July 1991 to March 1994, 25 consecutive patients with FSHF underwent OLT with preservation of portal and caval flow. All patients had severe confusion (n = 9) or coma (n = 16) with a mean(s.d.) clotting factor V of 13(5) per cent and a mean(s.d.) serum bilirubin level of 408(151) mumol/l. During the anhepatic phase, haemodynamic data showed a preservation of cardiac filling pressure, mean arterial pressure, and renal perfusion pressure, while the mean(s.d.) urine flow was maintained at 182(120) ml/h. Venous bypass was not required. There were three (12 per cent) deaths after the operation, and all survivors made a full neurological recovery. Normal postoperative creatinine values allowed the early use of baseline immunosuppression. The authors conclude that, in patients with FSHF, successful liver transplantation can be achieved with this technical procedure.

Adult↗
PubMed1995

Hepatitis C virus genotypes in French blood donors.

The prevalence of different hepatitis C virus (HCV) genotypes in HCV infected individuals and the relation between the HCV genotypes and the source of the infection are controversial. The aim of this study was to determine the HCV genotypes in French blood donors. Fifty-one anti-HCV positive blood donors were studied with detectable serum HCV RNA by nested polymerase chain reaction (PCR) using primers derived from the 5' non-coding region. For genotyping HCV, we used a method based on analysis of the restriction fragment length polymorphisms (RFLP) after amplification by PCR of the HCV non-structural 5 (NS5) genome domain. Using this technique, the genotypes of 39 of the 51 blood donors (76%) were determined. Three previously described genotypes were found: 19 blood donors were infected by HCV genotype I (37%), 14 were infected by HCV genotype II (27%), 3 were infected by HCV genotype III (6%), and 3 were coinfected by two genotypes (6%). All three blood donors infected with two different genotypes were intravenous drug abusers. A past history of intravenous drug abuse was more frequent in blood donors with HCV genotype I. However, there was no difference in alanine transaminase (ALT) levels, histological lesions, and RIBA-2 patterns in blood donors infected with either HCV genotype I or HCV genotype II. These findings indicate that most HCV genotypes isolated from French blood donors belong to HCV genotype I and HCV genotype II, and that risk factors for HCV infection may differ for different genotypes of HCV.

Adult↗