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Biomedical subjects

J P Bronowicki

Publications and source records attributed to J P Bronowicki.

At least 19 recordsLinked to original sources
PubMed2006

Effectiveness of interferon plus ribavirin combination in the treatment of naive patients with hepatitis C virus type 5. A French multicentre retrospective study.

AIM: To assess the rate of sustained virological response in naïve hepatitis C virus-type 5 patients treated by standard interferon or pegylated-interferon [corrected] (peg-interferon) and ribavirin combination for 48 weeks. PATIENTS AND METHODS: A total of 87 hepatitis C virus patients were included from 12 centres in France; 28 patients received interferon plus ribavirin and 59 were treated with peg-interferon plus ribavirin. RESULTS: Baseline characteristics were: mean age 58 +/- 11 years, sex ratio 1, 66% had metavir fibrosis score >or=F2, 21% were cirrhotics and 53% had pretherapeutic viral load >or=800,000 IU/mL. Sustained virological response was achieved in 64% and 58% of hepatitis C virus-5 patients treated with interferon and peg-interferon, respectively (NS). In adherent patients, sustained virological response was obtained in 75% of patients. Sustained virological response in hepatitis C virus-5 patients (60%) was significantly higher than sustained virological response in hepatitis C virus-1 patients (37%) (P = 0.0499) and not significantly different from sustained virological response in hepatitis C virus-2-3 patients (63%) (P = 0.8098). CONCLUSIONS: Combination therapy is effective in 60% of hepatitis C virus-5-infected patients. Sustained virological response seems better in hepatitis C virus-5 patients than in hepatitis C virus-1 patients, and is similar to that of hepatitis C virus-2-3 patients. More studies are needed to determine optimal duration of treatment in hepatitis C virus-5 patients.

Antiviral Agents↗
PubMed2006

Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b.

We compared sustained virological response (SVR) in chronic hepatitis C patients with severe fibrosis treated with pegylated interferon (Peg-IFN) alpha-2b 1.5 microg/kg/week or 0.75 microg/kg/week in combination with ribavirin 800 mg/day for 48 weeks. This was a multicentre randomized controlled study. SVR was observed in 44.5% (45/101) of patients treated with the standard dose of Peg-IFN and 37.2% (38/102) of patients treated with the low dose (NS). In patients with genotypes 1, 4 and 5, SVR was observed in 25.0% of patients who received the standard dose and 16.9% of patients who received the low dose of Peg-IFN (P = NS). In patients with genotypes 1, 4 and 5 and low viraemia, SVR was obtained in 27.3% of patients treated with the standard dose and 25.8% of patients treated with the low dose (P = NS). In the high-viraemia subgroup, SVR was obtained in 24.0% and 9.1% of patients, respectively. In patients with genotypes 2 and 3, SVR was similar in both groups (73.2%vs 73.0%). Thus, (1) patients with genotypes 2 and 3 and severe fibrosis can be treated with low dose of Peg-IFN and ribavirin, (2) this study suggests that patients with genotypes 1, 4 and 5 and high viraemia could receive a standard dose of Peg-IFN associated with ribavirin for 48 weeks, (3) side effects limit the efficacy of the treatment with standard dose of Peg-IFN in patients with genotypes 1, 4 and 5 and low viraemia, (4) more studies are needed for patients with genotype 2 or 3 to define the optimal duration (24 or 48 weeks) in patients with severe fibrosis.

Adult↗
PubMed2003

Reinforced interferon alpha-2b and ribavirin is more effective than standard combination therapy in the retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial.

Interferon-alpha (IFN) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a standard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were randomized. The reinforced group (n = 114) received IFN-2b 6 million units (MU) thrice weekly (TIW) and ribavirin for 48 weeks, and the nonreinforced group (n = 117) received IFN-2b 3 MU TIW and ribavirin for 24 weeks. The main outcome measure was a sustained virological response, defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment. This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group. At the end of follow-up, a sustained virological response was observed in 29 of the 98 patients (29.6%) in the reinforced group vs 16 of the 105 patients (15.2%) in the nonreinforced group (P = 0.014). In multivariate analysis, factors associated with a sustained virological response were treated with a reinforced regimen [odds ratio (OR) 2.9; P = 0.06] and genotype 2 or 3 (OR 8.8; P < 0.0002). A total of 160 patients had paired biopsies before and after treatment. Histological activity improvement was observed in 32 of 80 patients (40%) and fibrosis worsening in 26 of 80 patients (33%) in the reinforced group vs 13 of 80 (16%) and 19 of 80 (24%) in the nonreinforced group (P = 0.30 and 0.20, respectively). Hence in nonresponders, a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only.

Adolescent↗
PubMed2002

Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels.

OBJECTIVE: A significant proportion of individuals with chronic hepatitis C virus (HCV) infection have persistently normal alanine aminotransferase (ALT) levels. Although data are controversial, such patients usually have weaker histological damage and a lower progression rate of fibrosis. The aims of this study were: (1) to compare demographic, virological, and histological parameters of HCV patients with normal ALT values with those of HCV patients with elevated ALT levels; and (2) to determine whether HLA class II alleles contribute to the persistence of normal ALT levels in HCV patients. PATIENTS AND METHODS: Eighty three patients with chronic HCV infection and persistently normal ALT values (group 1) and 233 patients with chronic HCV infection and elevated ALT levels (group 2) were studied. Histological features were expressed using Knodell and Metavir scores. HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence specific oligonucleotides after genomic amplification. The kappa2 and Fisher's exact tests were used to compare discrete variables and phenotype frequencies between the two groups, and Wilcoxon's test was used for continuous variables. A multivariate logistic regression model was used to determine which variables predicted normal ALT values. RESULTS: ALT levels were correlated with the severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir index of fibrosis compared with 47% of patients in group 2 (p<0.001). A longer duration of infection (p<0.001) and increased DRB1*11 phenotype frequency (pc=0.03) were observed among patients with normal ALT. The two groups did not differ with regard to the mode of contamination or viral genotype. After logistic regression, young age (p=0.0008), female sex (p=0.01), long duration of infection (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with persistence of normal ALT. CONCLUSIONS: Our study confirms that patients with chronic hepatitis C and normal ALT levels have less severe liver disease than those with elevated ALT levels. This particular biochemical outcome may be explained, at least in part, by host immunogenetic factors such as the presence of HLA-DRB1*11.

Adult↗
PubMed2001

Early administration of vapreotide for variceal bleeding in patients with cirrhosis.

BACKGROUND: In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown. METHODS: We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding. The patients were randomly assigned to receive vapreotide (a 50-microg intravenous bolus followed by an infusion at a rate of 50 microg per hour for five days) or placebo within a mean (+/-SD) of 2.3+/-1.5 hours after admission. All the patients received endoscopic treatment a mean of 2.6+/-3.3 hours after the infusion was begun. After the exclusion of 31 patients whose bleeding was not caused by portal hypertension, there were 98 patients in each group. RESULTS: At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03). During the five-day infusion, the primary objective--survival and control of bleeding--was achieved in 65 of 98 patients in the vapreotide group (66 percent) as compared with 49 of 98 patients in the placebo group (50 percent) (P=0.02). The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04). Overall mortality rates at 42 days were not significantly different in the two groups. CONCLUSIONS: In patients with cirrhosis and variceal bleeding, the combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone as a method of controlling acute bleeding. However, the use of combination therapy does not affect mortality rates at 42 days.

Blood Transfusion↗
PubMed2001

Treatment of mild chronic hepatitis C with interferon alpha-2b: results of a multi-centre randomized study in 80 patients.

OBJECTIVE: The natural history of mild chronic hepatitis C is not well-known and the benefit of treating this form of the disease is not well-defined. We conducted a pilot study to answer this question. DESIGN: Mild chronic hepatitis C was defined by positivity for anti-HCV antibodies, detectable serum HCV RNA by PCR, and a Knodell score < or = 5 on a liver biopsy performed within the previous 6 months. Eighty patients from six centres were randomized into two groups receiving interferon alpha-2b, 3 MU three times a week for 6 months (group 1, n = 39) or no treatment (group 2, n = 41). Sustained response was defined by the loss of detectable serum HCV RNA at 6 months after therapy. RESULTS: The two groups were not different at entry with respect to age, sex ratio, source of infection, disease duration, genotype, viral load and Knodell score. One patient (group 1) was excluded from the study, while two patients in group 1 (5%) and seven in group 2 (17.1 %) did not complete the trial. A sustained response was observed in seven patients (18%) in group 1 versus none in group 2 (P < 0.01). The difference in mean Knodell score remained non-statistically significant between the two groups at the end of the study. Reduction or interruption of interferon was necessary in eight patients (24.2%). CONCLUSIONS: This first randomized controlled study in mild chronic hepatitis C shows a proportion of sustained responders to interferon alpha-2b similar to that observed in active chronic hepatitis C.

Adult↗
PubMed2000

Hepatitis B virus X gene variability in French-born patients with chronic hepatitis and hepatocellular carcinoma.

The polymorphism of the hepatitis B virus (HBV) X gene from patients born in Lorraine has been studied in serum samples from 22 HBV infected patients, 14 presenting with chronic hepatitis and 8 with hepatocellular carcinoma (HCC). Subtypes adw and ayw represented 21 of the 22 sequenced isolates. The sequence of the X gene of HBV strains from these patients differed from the ones of Far East origin by A to T(1678) and G to A(1759) changes for subtype ayw and C to T(1792) for adw. The expression of the preC region, as indicated by the detection of HBe antigen (HBeAg), was not observed in 11 patients. In 6 patients (3 HCC and 3 non HCC), the absence of HBeAg could be related to a stop codon at position 28. For the 5 remaining patients, the precore stop mutation at codon 28 was not evidenced but 3 out these 5 patients had mutations at nt 1764 and nt 1766 in the promoter of the preC/C gene. These two mutations were also observed in 2 patients with HBeAg, indicating that they are not implicated in the suppression of expression of this gene. Independently of the serotype, two main differences were noted between aminoacid (aa) sequences of chronic hepatitis and HCC related strains: first, twice as many aa changes were found in HCC patients than in chronic hepatitis B carriers (mean of aa changes per patient 4.1 vs. 2.0) and second, we found apparition of polar aa in HCC patients. Most mutations already described in patients from the Far East with HCC have been found in strains of patients from Lorraine. The changes K130M and V131I, considered as "hot spot mutations," were found in strains of HCC patients carrying an ayw subtype of the HBV genome but not in the ones of chronically infected patients. In contrast, strains of the adw subtype had these two changes in the two groups of patients. However when considering the 22 sequenced genes, these hot spot mutations were associated with HCC (P = 0.034).

Adolescent↗
PubMed1999

Permissiveness of human biliary epithelial cells to infection by hepatitis C virus.

The cellular tropism of hepatitis C virus (HCV) is an important but much debated issue. Permissivity to HCV of biliary cells has never been demonstrated. In this context, we used gallbladder epithelial cells (GBEC) as a model of the more proximal biliary epithelium. These cells were isolated from HCV-positive and -negative individuals and cultured for up to 40 days. Biliary cells from HCV-negative subjects were infected in vitro with various inocula. The retention of GBEC functional characteristics was assessed by the expression of cystic fibrosis transmembrane conductance regulator (CFTR). All 12 GBEC tested from HCV-negative patients were successfully infected by HCV. This was assessed by: 1) the detection of HCV-RNA positive and negative strands; 2) the detection of the viral capsid by immunofluorescence; and 3) the combination of single-strand conformation polymorphism (SSCP) and HVR1 sequence analysis demonstrating the distinct majoritary HCV genomes in serum and in GBEC. The level of HCV RNA in cell extracts and supernatants was low, but HCV infection was highly reproducible. Our results expand those showing the cellular tropism of HCV, and demonstrate the sensitivity of biliary cells to HCV infection. This might have an important impact in terms of pathogenesis and pathological features of HCV infection. In addition, given the easy access to these cells and the high reproducibility of in vitro infection, they should constitute an important tool for studies aimed at analyzing the issue of HCV penetration and neutralizing antibodies.

Base Sequence↗
PubMed1999

Nutritional value of proteins from edible seaweed Palmaria palmata (dulse).

Palmaria palmata (Dulse) is a red seaweed that may be a potential protein source in the human diet. Its protein content, amino acid composition, and protein digestibility were studied with algae collected every month over a 1-year period. Significant variations in protein content were observed according to the season: The highest protein content (21.9 +/- 3.5%) was found in the winter-spring period and the lowest (11.9 +/- 2.0%) in the summer-early autumn period. Most of the essential amino acids were present throughout the year. After 6-hour in vitro digestion in a cell dialysis using porcine pepsin and porcine pancreatin, the digestibility of proteins from Palmaria palmata crude powder, represented by dialyzed nitrogen, was estimated at 29.52 +/- 1.47%. Relative digestibility was 56%, using casein hydrolysis as 100% reference digestibility. In vitro digestibility of proteins extracted in water was analyzed by sodium dodecylsulfate polyacrylamide gel electrophoresis using either bovine trypsin, bovine chymotrypsin, pronase from Streptomyces griseus, or human intestinal juice. Dulse proteins were hydrolyzed to a limited extent, which confirmed a rather low digestibility. Hydrolysis rate was higher with trypsin and lower with chymotrypsin compared with the two other enzymatic systems, pronase and intestinal juice, respectively. The association of algal powder and protein extract to casein and bovine serum albumin, respectively, produced a significant decrease in the hydrolysis rate of the standard proteins. In conclusion, the digestibility of Palmaria palmata proteins seems to be limited by the algae non-proteic fraction.

Journal Article↗
PubMed1998

Hepatitis C virus persistence in human hematopoietic cells injected into SCID mice.

The issue of infection of peripheral blood mononuclear cells (PBMC) by the hepatitis C virus (HCV) has potentially important implications, but is still debated. We have used the severe combined immunodeficiency (SCID) mouse model to test for the persistence of HCV in PBMC. Hematopoietic cells isolated from 14 subjects infected by HCV were inoculated intraperitoneally into SCID mice. Serum and blood cell samples from these mice were obtained with a mean follow-up of 8 weeks. As controls, human fibroblasts and sheep PBMC, preincubated with a human HCV-positive serum, were inoculated concomitantly into mice and analyzed. HCV-RNA positive strands were detected in 7 of 26 serum samples and 8 of 26 cell fractions from SCID mice inoculated with HCV-positive PBMC, after 8 weeks of follow-up. In contrast, no HCV RNA was detectable in the 10 control mice. HCV-RNA negative strands were detected in only 2 of 10 tested samples from 2 mice, and both positive mice had been inoculated with PBMC from HCV-positive subjects with malignant hematopoietic syndrome. Our study offers strong evidence for the persistence of HCV infection in mononuclear cells. Our results are also consistent with a low rate of HCV multiplication. This SCID mouse model might therefore be useful in analyzing the mechanisms of HCV persistence in mononuclear cells.

Animals↗
PubMed1998

[Chemoembolization techniques for hepatocellular carcinoma in cirrhosis].

Transcatherter oily chemoembolisation, that should not be confused with other different and less effective techniques also called "chemoembolisation" is the most widely used therapy for loco-regional palliative treatment of hepatocellular carcinoma, which will become increasingly frequent, due to HCV infection; the cancer itself is often discovered at an advanced stage, when neoplastic extension precludes radical treatment that is liver transplantation. Performed with the best techniques, it offers a 1- and 5-yr survival of 60 and 30%, that is under confirmation by a randomized trial.

Carcinoma, Hepatocellular↗
PubMed1997

Lymphocyte reactivity to hepatitis C virus (HCV) antigens shows evidence for exposure to HCV in HCV-seronegative spouses of HCV-infected patients.

Lymphocyte reactivity against hepatitis C virus (HCV) antigens was studied in 20 couples in which 1 member had chronic hepatitis C. This was done to investigate the possibility of HCV transmission between spouses that was not followed by seroconversion. Twenty healthy subjects without any risk factors for HCV transmission served as negative controls. All the patients' spouses and the healthy controls were negative for HCV RNA and for anti-HCV antibody. Lymphocytes were cultured with recombinant HCV core and nonstructural antigens (c22, c33, c100, c200, and NS5) and with control antigens (sperm whale myoglobin, chicken lysozyme, and superoxide dismutase). Lymphocytes from 10 patients and 4 seronegative spouses proliferated in the presence of at least one HCV antigen. No proliferation was shown with nonspecific antigens or in the control group. This study gives evidence for possible in vivo priming with HCV antigens that did not lead to seroconversion in spouses of HCV-positive patients.

Adult↗
PubMed1997

Prospective evaluation of protein bound vitamin B12 (cobalamin) malabsorption in the elderly using trout flesh labelled in vivo with 57Co-cobalamin.

BACKGROUND: The frequency of dietary protein bound vitamin B12 malabsorption in elderly patients remains controversial. AIMS: To evaluate this malabsorption in elderly hospitalised patients using a modified Schilling test. PATIENTS: Fourteen elderly patients with low B12 blood levels were prospectively selected from 394 hospitalised patients. METHODS: The modified Schilling test was performed with trout labelled in vivo. RESULTS: The test was normal in five healthy elderly subjects, in 7/8 patients with pancreatic insufficiency, and in nine non-elderly patients with antral gastritis. The low decision limit was established at 3.3% (median 4.8%). From the 14 elderly patients with low B12 prospectively selected from 394 hospitalised patients, seven had a real deficiency with anaemia and an increased homocysteine and/or methylmalonate serum level. The modified Schilling test showed malabsorption in five of these patients, including two in which the standard Schilling test was normal, and three in which the standard Schilling test was partially corrected by an intrinsic factor. CONCLUSIONS: Protein bound vitamin B12 malabsorption was detected in at least 0.5% of elderly hospitalised patients, using the labelled trout flesh absorption test.

Adult↗
PubMed1997

Autoantibodies in pernicious anemia type I patients recognize sequence 251-256 in human intrinsic factor.

Pernicious anemia is an organ-specific autoimmune disease characterized by cobalamin deficiency, megaloblastic anemia, neuropathy, and autoimmune gastritis with anti-intrinsic factor autoantibodies. Type 1 anti-intrinsic factor autoantibodies block the cobalamin binding site of the intrinsic factor, a gastric protein required for the assimilation of cobalamin. The aim of our study was to identify the epitope domain of type 1 antibodies. Different series of peptides derived from the intrinsic factor sequence were synthesized and tested for antibody binding in enzyme-linked immunosorbent assay, radioisotope assay, gel filtration, and SDS-PAGE autoradiography. One of these peptides, named IF-R7 (the intrinsic factor aminoacid sequence 251-265), showed a type 1 antibody binding activity and inhibited, in vitro, their blocking activity with Ki at 2.3 microM. The cross-linking of IF-R7 to beta-lactoglobulin produced type 1 anti-intrinsic factor antibodies in immunized sheep. In vivo Schilling tests performed on guinea pigs also revealed IF-R7 peptide inhibition of type 1 antibody blocking activity. 256Ser, 258Lys, 262Tyr and 265Val of the IF-R7 were essential for the epitope recognition. Reactivity with type 1 antibodies was found in IF-R7 homologous peptides from herpesvirus Saimiri and from pathogenic Escherichia coli. In conclusion, the epitope of type 1 anti-intrinsic factor autoantibodies is located in the 251-265 amino acid sequence of the protein. The identification of this epitope will enable the definition of an experimental animal model of anti-IF autoimmunity in order to study the pathogenesis of pernicious anemia.

Amino Acid Sequence↗
PubMed1997

[Comparison of immunogenicity of vaccination and serovaccination against hepatitis B virus in patients with alcoholic cirrhosis].

OBJECTIVES: The association of anti-HBs immunoglobulins and anti-HBV vaccine could increase the immunogenicity of the latter. The aim of this prospective randomized trial was to compare the immunogenicity of anti-HBs vaccination and serovaccination in alcoholic patients with cirrhosis. METHODS: Alcoholic patients with cirrhosis were randomized in 2 groups: a) Vaccination group: 3 i.m. injections of GenHevac B followed by one booster at month 9; b) Serovaccination group: same vaccination schedule followed by one i.m. injection of anti-HBs immunoglobulins (500 IU). RESULTS: Twenty-five patients (17 males and 8 females, mean age 56 years) were included in the study: 13 received a vaccination and 12 received a serovaccination. After 12 months, the seroconversion rates were 69% and 67% in vaccination and in serovaccination groups, respectively. The predictive factors of non responsiveness were as following: Child B cirrhosis, low number of CD8, a high CD4/CD8 rate, the existence of HLA DR7 antigen, and the absence of HLA DR1 antigen. CONCLUSION: In alcoholic patients with cirrhosis, serovaccination does not increase the immunogenicity of anti-HBs vaccination and should not be recommended.

Female↗