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Biomedical subjects

J C Trinchet

Publications and source records attributed to J C Trinchet.

At least 73 records · Page 4Linked to original sources

Chemoattractant and opsonic activity in ascitic fluid. A study in 47 patients with cirrhosis or malignant peritonitis.

We studied prospectively the ascitic fluid of 47 patients. Thirty-five were cirrhotics (group A) and 12 had malignant peritonitis (group B). All ascitic fluid samples were initially uninfected. We measured opsonic activity by a chemiluminescent assay, and chemoattractant activity by the under agarose technique. We also measured ascitic concentrations of C3, C4, fibronectin, C-reactive protein, immunoglobulins G, A and M and total proteins. All patients were followed throughout the presence of ascites. None of the group B patients developed peritoneal infection, nor did 23 of the group A patients (group A2). Twelve group A patients (group A1) developed spontaneous bacterial peritonitis (SBP), four of them with recurrence. All indices except immunoglobulins A and M were significantly different between group A and group B patients. Comparing group A1 and group A2, only chemoattractant activity and concentrations of total proteins and C3 were significantly lower in group A1. Using a multivariate analysis with Cox's model, only C3 concentration had an independent predictive value for occurrence of SBP in cirrhotic patients.

Aged↗

Serum type I collagen and N-terminal peptide of type III procollagen in chronic hepatitis. Relationship to liver histology and conventional liver tests.

The aim of this study was to compare serum N-terminal peptide of type III procollagen to aminotransferases and gamma-globulins as a marker for histological activity in patients with chronic hepatitis and to assess the role of type I collagen, a new serum marker, as a marker of fibrosis in these patients. Sixty patients with biopsy-proven chronic hepatitis were included in this study. Liver disease was virus B-related in 29, autoimmune in five, drug-induced in five, and of unknown etiology in 21. Each biopsy was independently assessed by two liver pathologists. Two histological scores, a score of activity and a score of fibrosis, were established. Serum N-terminal peptide of type III procollagen and type I collagen were assayed by liquid phase RIA. Significant correlations were noted between serum N-terminal peptide of type III procollagen and scores of activity (r = 0.70, p less than 10(-4)) and fibrosis (r = 0.45, p = 0.0005), and between serum type I collagen and scores of activity (r = 0.46, p = 0.0004) and fibrosis (r = 0.67, p less than 10(-4)). When the correlation between scores of activity and fibrosis (r = 0.52, p = 10(-4)) was considered by partial correlation, serum N-terminal peptide of type III procollagen was correlated with the score of activity (r = 0.63, p less than 10(-3)) but not with the score of fibrosis, and serum type I collagen was correlated with the score of fibrosis (r = 0.58, p less than 10(-3)), but not with the score of activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pathogenesis of liver cirrhosis in alcoholic patients: histological evidence for hepatitis C virus responsibility.

Hepatitis C virus (HCV) has been proposed to be a cofactor in the pathogenesis of cirrhosis in patients with chronic alcoholism. The demonstration of a different liver histological pattern in anti-HCV positive patients might provide additional evidence. We studied 164 patients with chronic alcoholism, and histologically proven cirrhosis. For all of them, serum samples were collected at the time of a liver biopsy and stored at -80 degrees C. Testing for anti-HCV antibodies was done using the Ortho Diagnostic Systems Anti-HCV ELISA test. Only reproducible results were considered positive. A semi-quantitative assessment of seven histological parameters was made independently on liver biopsy samples. In the study group, 29 patients (18%) had anti-HCV antibodies. When compared with anti-HCV negative patients, both groups had similar ALT and AST seric activities. Anti-HCV positive patients had a greater score of mononuclear cells infiltrate (0.71 +/- 0.57 vs 0.41 +/- 0.52; p less than 0.05) and a lesser score of alcoholic hepatitis (0.19 +/- 0.57 vs 0.74 +/- 0.74; p less than 0.005). The scores for steatosis, perisinusoidal and perinodular fibrosis, and hepatocellular necrosis were similar in the two groups. In anti-HCV positive patients, with a clearly positive recombinant immunobinding assay (RIBA, Chiron-Ortho Diagnostic Systems), a greater score for hepatic necrosis and a lesser one for fibrosis were demonstrated. Among the seven patients with active cirrhosis, six were anti-HCV positive. Therefore, HCV is likely to play a role in the pathogenesis of liver damage in a few patients with alcoholic cirrhosis, especially, those with active cirrhosis.

Adult↗

Preventive therapy of first gastrointestinal bleeding in patients with cirrhosis: results of a controlled trial comparing propranolol, endoscopic sclerotherapy and placebo.

Propranolol and endoscopic sclerosis of esophageal varices are the two approaches currently used in prophylaxis of the first gastrointestinal hemorrhage in the cirrhotic patient. One hundred twenty-six cirrhotic patients with esophageal varices and no histories of bleeding were included in the trial regardless of the gravity of the cirrhosis or the size of the esophageal varices. Patients with hepatocarcinomas or other cancers, clearly impossible follow-up, previous treatment for portal hypertension or contraindication to beta-blockers were excluded. After randomization, 43 patients received propranolol twice daily at a dose reducing the heart rate by 25%; 42 patients were treated with intravariceal and extravariceal injections of Polidocanol; 41 control patients received vitamin K orally as placebo. The patients were seen at 3-mo intervals for 2 yr. On entry to the trial the three groups were comparable in terms of clinical and biological parameters, including size of esophageal varices (grade I = 51, grade II = 54, grade III = 17), Child-Pugh classification (A = 29, B = 61, C = 32) and the origin of cirrhosis (alcoholic in 79% of cases). Twenty-four patients bled (two bled in the propranolol group, nine bled in the endoscopic sclerosis of esophageal varices group and 13 bled in the placebo group). Actuarial estimates (Kaplan-Meier) of the time of onset of first bleeding showed that the differences were significant between propranolol and placebo (p less than 0.004) and between propranolol and sclerotherapy (p less than 0.03) but not between sclerotherapy and placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal and Gastric Varices↗

Ursodeoxycholic acid for primary sclerosing cholangitis.

The effects of ursodeoxycholic acid (UDCA, 750-1250 mg/day) were evaluated prospectively in 15 patients with primary sclerosing cholangitis (PSC). Five patients had associated inflammatory bowel disease. After 6 months of treatment, the proportion of patients suffering from fatigue or pruritus decreased from 60% to 20% and from 33% to 20%, respectively. No exacerbation of associated disorders was observed. Serum alkaline phosphatase levels (normal less than 100 IU/l) decreased from 401 +/- 53 to 222 +/- 42 (mean +/- S.E.; p less than 0.001), those of gamma-glutamyl transpeptidase, (normal less than 40 IU/l) from 520 +/- 89 to 185 +/- 32 (p less than 0.001) and those of alanine aminotransferases, (normal less than 30 IU/l) from 79 +/- 12 to 42 +/- 6 (p less than 0.02). In three patients, the discontinuation of UDCA was associated with an aggravation of the liver test results. In conclusion, this study shows that 6 months of treatment with UDCA leads to clinical and biochemical improvements in patients with PSC. These results suggest that UDCA could be an effective treatment for PSC, and may justify a controlled therapeutic trial.

Adult↗

Radioimmunoassay of type I collagen that mainly detects degradation products in serum: application to patients with liver diseases.

This radioimmunoassay for type I collagen mainly detects degradation products of the molecule in human serum samples. Type I collagen antigenicity in serum can be separated into two peaks by gel-filtration chromatography. The larger form represents collagen molecules (as shown by immunoblotting experiments), and (or) type I collagen with aminoterminal propeptide or intact procollagen molecules. The smaller form, the exact nature of which is not known, is quantitatively the principal antigenic form and is derived from degradation of type I collagen. The concentration of type I collagen in serum is increased mainly in cirrhotic patients, with or without active liver disease, but also somewhat in alcoholic patients without cirrhosis.

Adult↗

Liver collagen mRNA and serum amino-terminal peptide of type III procollagen (PIIINP) levels in patients with alcoholic liver disease.

We have investigated the alpha 1 (I), alpha 2 (I) and alpha 1 (III) liver collagen mRNA levels in 38 patients with alcoholic liver disease. The patients were divided into 3 groups according to the severity of their liver disease. Liver collagen mRNA levels were estimated by densitometric analysis after hybridization with the corresponding cDNA. Serum amino-terminal peptide of type III procollagen (PIIINP) was determined by radioimmunoassay in 30 patients. The results indicated that there was no increase but rather a decrease in the liver alpha 1 (I), alpha 2 (I) and alpha 1 (III) collagen mRNA in patients with the most severe liver lesions as compared to those with minimal changes. This decrease was significant for alpha 2 (I) and alpha 1 (III) cDNA probes. In contrast, serum PIIINP levels showed a positive correlation with the severity of the disease. Thus this study indicates that collagen accumulation in the liver as well as elevation of the serum PIIINP during the development of alcoholic liver disease probably reflects posttranscriptional events in collagen synthesis.

Collagen↗

[Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients].

A randomized double-blind trial of silymarin versus placebo was carried out in 116 patients with histologically proven alcoholic hepatitis, 58 of them with cirrhosis. Patients were not included in case of hepatic encephalopathy, contraindication to percutaneous liver biopsy, hepatocellular carcinoma, evident lack of discipline or refusal to enter the trial. Fifty-seven patients received silymarin orally 420 mg/day and 59 received placebo during 3 months. Biologic parameters were assessed in the serum, and a percutaneous liver biopsy was obtained at the start of the trial and 3 months later. Histologic scores of alcoholic hepatitis and fibrosis were established on each biopsy specimen by two independent pathologists. The 2 groups were comparable at inclusion; 26 p. 100 of patients were lost to follow-up at 3 months, abstinence was obtained in 46 p. 100 of patients at the end of the trial. These percentages were similar in the two groups. Four patients died of hepatic failure during the trial, 3 in the placebo group. Significant improvement in the score of alcoholic hepatitis and serum amino transferase activity, was noted in both groups during the trial, irrespective of treatment with silymarin or placebo. No side-effects were noted. Our results suggest that silymarin 420 mg/d is not clinically relevant in the treatment of moderate alcoholic hepatitis.

Double-Blind Method↗

Treatment of alcoholic hepatitis with colchicine. Results of a randomized double blind trial.

A randomized double-blind trial of colchicine vs placebo was conducted in 67 patients with histologically proven alcoholic hepatitis, 33 of whom had cirrhosis. Patients with hepatic encephalopathy, ascites, protracted prothrombin time, severe thrombocytopenia, hepatocellular carcinoma, evident lack of discipline or refusal to participate in the trial were not included. Thirty-three patients received colchicine (1 mg/day) and 34 received placebo for 6 months. Blood parameters including N-terminal peptide of type III procollagen were assessed in the serum, and a percutaneous liver biopsy was performed at the start of the trial and after 3 and 6 months. Alcoholic hepatitis and fibrosis scores were established for each biopsy specimen. Twenty-eight percent of patients were lost to follow-up at 3 months, and fifty-two percent at 6 months. One patient died of liver failure. Fifty-eight percent of patients were abstaining from alcohol at 3 months and fifty percent at 6 months. No significant effect of treatment was noted. Nevertheless, improvement in alcoholic hepatitis core at 3 months was more important in the colchicine group than in the placebo group. No side-effects were noted except transient diarrhea. Our results suggest that colchicine has no important effect on the course of alcoholic hepatitis. A trial including of at least 260 patients might be necessary for the observed alcoholic hepatitis score difference at 3 months, favoring colchicine, to be statistically significant.

Colchicine↗

[Serum laminin and portal pressure in alcoholic cirrhosis. A study of 39 patients].

A correlation between serum laminin, a glycoprotein found in basement membranes, and hepatic wedge pressure has previously been reported in a small number of patients with various liver diseases. To study this relationship in patients with alcoholic cirrhosis, we measured the wedge hepatic pressure and venous gradient, in comparison with serum concentrations of laminin and collagen metabolism products: N-terminal peptide of type III procollagen, collagen type I, and collagen type III in 39 patients. A statistically significant correlation was observed between serum laminin and wedged hepatic pressure (r = 0.529; p less than 10(-3] or hepatic venous gradient (r = 0.482; p = 0.002). By contrast, no statistically significant correlation was found between hemodynamic parameters and serum concentrations of N-terminal peptide of type III procollagen, collagen type I or collagen type III. These results suggest that, in patients with alcoholic cirrhosis, portal pressure may be estimated by serum concentration of laminin, and that perisinusoidal fibrosis, especially basement membrane thickening, may play an important role in the pathogenesis of portal hypertension in these patients.

Blood Pressure↗

[Fibronectin in the ascitic fluid: its diagnostic significance].

We studied fibronectin concentration in the ascitic fluid of 102 patients, 71 with cirrhosis, 13 with hepatocellular carcinoma, 12 with malignant peritonitis, and six with miscellaneous disease. Fibronectin concentrations in the first three groups were 45 +/- 45 mg/l, 54 +/- 84 mg/l, and 144 +/- 123 mg/l, respectively. The difference between patients with cirrhosis and malignant peritonitis was significant (p less than 0.01). However, fibronectin concentration greater than 100 mg/l had a sensitivity of 58 per cent and a specificity of 86 per cent for the diagnosis of malignant peritonitis. Ascitic fluid protein content over 30 g/l had the same sensitivity and specificity was 90 per cent. Among cirrhotic patients, high fibronectin concentrations were demonstrated in those with long-standing ascites (m = 134 +/- 58 mg/l) whereas the lowest concentrations were found in patients with severe hepatocellular failure (m = 12 +/- 9 mg/l). Concentrations were significantly different, according to whether or not spontaneous bacterial peritonitis occurred later (20 +/- 13 mg/l versus 52 +/- 49 mg/l); 83 per cent of patients with spontaneous bacterial peritonitis during their clinical course had initial fibronectin concentrations above 30 mg/l in their ascites. We conclude that: 1) measurement of fibronectin concentration in ascitic fluid is of poor diagnostic value for discrimination between malignant and non malignant ascitic, 2) low concentrations of fibronectin are associated with the occurrence of spontaneous bacterial peritonitis in cirrhotic patients. Hypothetically, the quantitative defect of fibronectin could be responsible for bacterial opsonization impairment in these patients.

Ascitic Fluid↗

[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↗

[Does oral zinc improve the cellular immunity of patients with alcoholic cirrhosis?].

A depressed response to delayed hypersensitivity skin tests is frequent in patients with alcoholic cirrhosis. Immune dysfunction in these patients is presumably dependent on nutritional factors. Zinc deficiency, a common finding in alcoholic cirrhosis, inhibits cellular immunity and might be one of these factors. The aim of our study was to show that zinc supplementation may improve cellular immunity in patients with alcoholic cirrhosis. We therefore compared 2 groups of patients: patients in the treated group (n = 18) had a daily oral intake of zinc-sulfate, 200 mg, during 2 months, patients in the non treated group (n = 20) received no supplementation. Both groups had a free diet. Delayed hypersensitivity skin tests to 7 antigens were performed with the Multitest IMC System at the beginning and at the end of the study. The immunity score was determined by the number of tests producing a skin induration greater than 2 mm. The evolutive index, calculated in each patient, was the difference between the final and initial immunity scores. The 2 groups were similar for all studied parameters. Cumulated immunity scores improved from 35 to 53 in treated patients (p less than 0.02), and from 42 to 44 (NS) in non treated patients. The evolutive index was 1 +/- 1.4 in treated patients and 0.1 +/- 1 in non treated patients (p less than 0.05). We conclude that in patients with alcoholic cirrhosis, daily intake of zinc sulfate, 200 mg, improves responsiveness to delayed hypersensitivity skin tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Influence of diazepam premedication on upper digestive fiberscopy. 81 cases].

Upper gastrointestinal endoscopy is routinely used to follow up patients with digestive disease. The influence of premedication with diazepam on the procedure and on patients' acceptance of a second endoscopy was evaluated in a double-blind trial conducted on 81 patients randomized to 3 types of intravenous premedication: placebo (group A, 29 patients), diazepam 5 mg (group B, 27 patients) and diazepam 10 mg (group C, 25 patients). Endoscopy was performed under unfavourable conditions (refusal or agitation) in 12, 4 and 1 patients respectively of groups A, B and C (P less than 0.02). Out of 65 patients questioned one month later, 1 (group A) sternly refused a second endoscopy, 10 accepted unreservedly (O in group A, 4 in group B, 6 in group C; P less than 0.05 between A and C) and 54 accepted reluctantly. To find out whether diazepam was beneficial by impairing memory, a memory score on duration of the procedure was established; there were no significant differences between the three groups (P less than 0.001), but they did not correlate with the patients' acceptance of a second endoscopy. It is concluded that premedication with diazepam 10 mg i.v. makes upper gastrointestinal endoscopy easier to perform and facilitates acceptance of a repeat endoscopy 1 month later. This effect is probably independent of the impairment in memory induced by diazepam.

Diazepam↗