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J B Nousbaum

Publications and source records attributed to J B Nousbaum.

At least 19 recordsLinked to original sources
PubMed2000

The protein kinase-interacting domain in the hepatitis C virus envelope glycoprotein-2 gene is highly conserved in genotype 1-infected patients treated with interferon.

The hepatitis C virus (HCV) envelope glycoprotein-2 inhibits the interferon (IFN)-induced, double-stranded RNA-activated protein kinase (PKR) via the PKR eukaryotic initiation factor-2alpha phosphorylation homology domain (PePHD). The present study examined the genetic variability of the PePHD in patients receiving IFN therapy. The PePHD from 12 HCV genotype 1 (HCV-1)-infected patients receiving daily IFN therapy was amplified by reverse-transcriptase polymerase chain reaction and analyzed by direct and clonal sequencing. The PePHD was highly conserved in 38 HCV GenBank isolates. There was no difference in pretreatment PePHD sequences isolated from IFN responders versus nonresponders. The major PePHD quasi-species variant did not change after 6 weeks of daily IFN therapy, and in 1 patient the major quasi-species variant did not change during 9 months of observation. Sequencing of 25 pretreatment PePHD clones from 3 patients confirmed that there was extremely low sequence variability surrounding the PePHD. The PePHD is highly conserved in HCV-1-infected IFN responders and nonresponders and does not appear to evolve in response to IFN therapy.

Amino Acid Sequence↗
PubMed2000

Epidemiology and course of acute upper gastro-intestinal haemorrhage in four French geographical areas.

OBJECTIVE: To compare incidence rates and epidemiological characteristics of acute upper gastrointestinal haemorrhage (AUGIH) in France with those of other European studies. DESIGN: Population-based multi-centre prospective survey. SETTING: 29 public hospitals and 96 private specialists in gastroenterology in four administrative areas in France during 1996. SUBJECTS: A total of 2133 AUGIH patients 18 years and over were included in the six-month study. OUTCOME MEASURES: Incidence and mortality. RESULTS: The overall incidence in France was 143 cases per 100000 persons per year, classified as out-patients (16%), emergency admissions (59%) and in-patients (25%). The incidence rates increased with age except for in-patients, and were higher in males. Peptic ulcer (36.6%), varices (13.7%) and erosive disease (12.3%) were the most frequent diagnoses. In 677 patients (31.7%), aspirin, antiinflammatory drugs or corticosteroids were taken on the 7 days before bleeding. The overall mortality (out-patients excluded) was 14.3% (10.7% for emergency patients and 23% for in-patients). Mortality was associated with comorbidities (especially malignancies, cirrhosis, asthma or respiratory deficiency), was lower in emergency patients using non-steroid anti-inflammatory drugs, and higher in in-patients using corticosteroids. CONCLUSIONS: In France, patients with AUGIH are frequently managed as out-patients. Gastrotoxic drug use is frequently associated with AUGIH and constitutes a strategic opportunity for preventive treatment. Discrepancies between countries are not clearly explained either by demographic factors or by drug use, but this may be related to the emphasis on AUGIH in in-patients.

Acute Disease↗
PubMed2000

Antibody response of patients with Helicobacter pylori-related gastric adenocarcinoma: significance of anti-cagA antibodies.

The aim of this study was to search for a specific antibody pattern in sera from patients suffering from Helicobacter pylori-related gastric adenocarcinoma (GAC). The serological response of 22 patients suffering from GAC, 31 patients with gastroduodenal ulcer, and 39 asymptomatic subjects was analyzed using immunoblotting performed with three H. pylori strains: strain ATCC 43579; strain B110, isolated from a patient with ulcers; and strain B225, isolated from a patient with GAC. In addition, the latex agglutination test Pyloriset Dry was used to analyze ambiguous sera. H. pylori seropositivity was 75% in the GAC group, 61.3% in the ulcer group, and 56.4% in the asymptomatic group. Anti-CagA antibodies were found more often in the GAC group (48.8%) and in the ulcer group (47.3%) than in the asymptomatic group (21.2%). These percentages depended on the strain used as an antigen: in the GAC group, the anti-CagA frequencies were 93.3, 40, and 13.3% with strains B225, B110, and ATCC 43579, respectively. Thus the presence of anti-CagA antibodies was increased in patients suffering from H. pylori-related GAC, in particular when the CagA antigen was from a GAC strain. These data suggest the existence of a CagA protein specifically expressed by H. pylori strains isolated from GAC patients.

Adenocarcinoma↗
PubMed1999

Anti-inflammatory drugs and variceal bleeding: a case-control study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices is a major complication of cirrhosis of the liver. AIMS: To investigate the role, using a case-control study, of NSAIDs in first bleeding episodes associated with oesophageal or cardial varices in cirrhotic patients. PATIENTS/METHODS: A structured interview was conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal varices and 75 cirrhotic controls with oesophageal varices who had never bled. RESULTS: Cirrhotic patients who were admitted for bleeding related to portal hypertension were more likely to have used NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases (21 of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p = 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds ratio = 2. 9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001, odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables independently associated with the risk of bleeding. CONCLUSIONS: Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone.

Adult↗
PubMed1999

[Hemorrhaging eso-gastro-duodenal ulcers: epidemiology and management. A multicenter prospective study].

UNLABELLED: The aim of this study was to estimate the incidence, and to describe the characteristics and medical care in patients with bleeding upper gastrointestinal ulcers in the general population. PATIENTS AND METHODS: A study was performed over six months in 1996 in 4 French geographical areas: Finistère, Gironde, Seine-Maritime, and the Somme (3 million people minimum 18 years). All public or private hospitals, and specialist gastroenterologists in private practice participated in the study, based on a standardized questionnaire. RESULTS: Over 6 months 793 patients with bleeding ulcers were identified, corresponding to 27 per 100,000 inh./year or 24,000 cases in France. Most patients were men (60%) and 40.1% were 75 years and older. The ulcer was oesophageal (6%), gastric (47%), or duodenal (69%). In 406 patients (51.2%) a chronic disease was present (cancer, cirrhosis, circulatory, respiratory or cardiac disease). In 237 cases (29.9%) the ulcer occurred in patients, 453 patients (57.1%) were admitted and 103 patients (13%) were managed as outpatients. Gastrotoxic drugs were taken by 349 patients (44%): non steroidal anti-inflammatory drugs (18.7%), aspirin (21.2%, including 2/3 with doses under 330 mg/day), corticosteroids (7.8%) and 24.3% had anticoagulant therapy. Patients were managed in university hospitals (39.3%), other public or non profit hospitals (44.2%) or private hospital (16.5%) with geographical differences between the 4 areas. Therapeutic endoscopy was performed in 16.9% and a surgical procedure was performed in 5.9%. The mortality rate (outpatients excluded) was 13.5% (n = 93), but only 2% (n = 16) of death were associated with a bleeding ulcer: mortality was higher in inpatients (24.1%) than in out patients (8.1%). A chronic disease was also associated with higher mortality (17.9% versus 8.1%). CONCLUSION: Bleeding ulcers are frequent and severe, especially in inpatients or associated with chronic conditions. A gastrotoxic drug used is found in about fifty percent of the cases.

Adolescent↗
PubMed1998

[Genomic subtypes of hepatitis C virus: epidemiology, diagnosis and clinical consequences].

Hepatitis C virus demonstrates a high degree of variability HCV isolates have been classified into at least six genotypes, according to the percentage of nucleotide sequence homology. Geographical differences in the distribution of virus genotypes are well documented. Types 1, 2 and 3 are the major types observed in Japan, Western Europe and North America; type 4 has been found in Central and Northern Africa and in the Middle East; type 5 has been described in South Africa, type 6 in South-East Asia. The relative prevalence of these genotypes varies between different regions. In the Indian subcontinent, subtype 1b seems to be the most prevalent type, but many isolates have been described, related to genotype 3, in Northern and Southern India, Pakistan and Nepal. HCV genotypes may have potential clinical implications: a) the association with the severity of liver disease is still controversial; b) the association between some genotypes, particularly 1b, and a poor response to interferon alpha therapy has been well established; c) genotyping may be useful for identifying some unusual modes of transmission of the virus. Finally, the variability of HCV virus has major implications for the design of new vaccines strategies since there is no cross-protection between different HCV types.

Genotype↗
PubMed1997

Phenotype-genotype correlation in haemochromatosis subjects.

Haemochromatosis is a common autosomal recessive genetic disorder of iron metabolism. A candidate gene was recently identified (HLA-H) and two amino acid substitutions (C282Y and H63D) were characterized. Haemochromatosis probands (n = 478) from Brittany were selected from their iron status markers, primarily serum iron, serum ferritin and transferrin saturation. We investigated the relationships between haemochromatosis phenotype and genotypes at the HLA-H locus and surrounding markers. As already reported, we observed that the C282Y substitution is unambiguously associated with the haemochromatosis phenotype, haemochromatosis patients homozygous for the substitution (Tyr/Tyr) accounting for 81.2% of all haemochromatosis patients. A clear heterogeneity in serum ferritin and transferrin saturation values, and in iron removed by phlebotomy was observed among haemochromatosis patients that is correlated with the presence of two subgroups of individuals homozygous and non-homozygous for the mutant allele C282Y, the latter being characterized by lower phenotypic values. In this subgroup, sequencing did not reveal any other mutation in the HLA-H gene, hence the genotype remained unclear. Thus, an additional non-genetic cause, other mutations or another gene can not be excluded as explanations for the results in these patients.

Female↗
PubMed1996

Molecular analysis of the TP53 gene in Barrett's adenocarcinoma.

The TP53 gene is the most frequently mutated gene in human cancers. Barrett's esophagus provides an excellent model by which to understand the genetic events that lead from dysplasia to cancer. We screened for mutations in the TP53 gene by a combination of denaturing gradient gel electrophoresis and DNA sequencing in ten cases of adenocarcinoma arising in Barrett's mucosa. We have identified missense mutations in five of the ten samples, three transitions (R282W, G245S, R248W) and two transversions (E286Q and C176F). In one case we have analyzed biopsy specimens taken from the same site, one year before the patient developed an intra mucosal carcinoma. The mutation that was identified in this high grade dysplastic area was identical to that detected in the cancer. This would suggest TP53 mutations occur as an early genetic event in the development of Barrett's adenocarcinoma.

Adenocarcinoma↗
PubMed1995

Hepatitis C virus type 1b (II) infection in France and Italy. Collaborative Study Group.

OBJECTIVE: To analyze the distribution of hepatitis C virus (HCV) genotypes among patients positive for antibody to HCV (anti-HCV) according to age, severity of liver disease, and duration of infection; to investigate the influence of HCV genotypes on response to interferon-alpha therapy; and to study HCV viremia levels in relation to genotypes and severity of liver disease. DESIGN: Cross-sectional study. SETTING: 3 university hospitals and 2 research units. PATIENTS: 3 groups of French and Italian patients with chronic HCV infection and detectable serum HCV RNA: Group 1 included 35 patients with hepatocellular carcinoma; group 2, 71 patients with cirrhosis who did not have hepatocellular carcinoma; and group 3, 114 patients with chronic active hepatitis. 106 of the patients with chronic hepatitis or cirrhosis were treated with interferon-alpha (3 MU subcutaneously 3 times/wk for > or = 6 months). MEASUREMENTS: Genotyping by polymerase chain reaction with capsid-specific primers; serum HCV RNA by branched DNA (bDNA) signal amplification. RESULTS: Hepatitis C virus genotype 1b (II) was the most prevalent genotype (61.8%). In a univariate analysis, it was associated with older age (< 40 years, 47.4%; > or = 60 years, 80.4%; P = 0.001), longer duration of disease (< or = 10 years, 40.4%; > or = 20 years, 86.7%; P = 0.005), and cirrhosis with or without hepatocellular carcinoma (78.4% compared with 53.8% for chronic hepatitis; P < 0.001). Viremia levels did not differ between patients infected with HCV type 1b (II) and those infected with other HCV genotypes. Patients with HCV type 1b (II) responded to interferon-alpha therapy significantly less than did patients with other HCV genotypes (P = 0.01). In a multivariate analysis, age and cirrhosis were independently associated with HCV genotype 1b (II). Genotype and HCV viremia level were independent predictors of response to interferon-alpha therapy. CONCLUSIONS: The prevalence of HCV genotypes in French and Italian patients has been changing; the prevalence of HCV type 1b (II) infection has progressively decreased, although it still accounts for most HCV-related cirrhosis and hepatocellular carcinoma. High HCV viremia levels and HCV genotype type 1b (II) are independent predictors for poor response to interferon-alpha therapy and should be considered in the management of patients with HCV infection.

Adult↗
PubMed1995

The changing relative prevalence of hepatitis C virus genotypes: evidence in hemodialyzed patients and kidney recipients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection by the genotype 1b is significantly associated with a lower rate of response to interferon alfa and with severe liver disease (cirrhosis and hepatocellular carcinoma). This may reflect different intrinsic properties of this genotype 1b and/or chronological differences in the epidemiology of HCV genotypes. To address the issue of variations in genotypes prevalence, we studied in the present report the HCV genotypes of 60 hemodialyzed and kidney recipients according to the date of hemodialysis. METHODS: Anti-HCV antibodies were tested by a second-generation assay (enzyme-linked immunosorbent assay 2 and recombinant immunoblot assay 2). HCV RNA was detected by reverse-transcription polymerase chain reaction. Genotyping was performed by hybridization of type-specific probes to the amplified product from the 5' untranslated region. RESULTS: Genotype 1b accounted for more than two thirds of HCV infection in patients who underwent dialysis before 1977 but less than one third in those hemodialyzed after 1985. In contrast, other genotypes (3a, 4a, 5a) appeared in the 1980s. CONCLUSIONS: These data, obtained in an homogenous group of patients, show a changing pattern of HCV genotype prevalence over time and should be considered when discussing the potential clinical implications of HCV genetic variability.

Female↗
PubMed1995

Ciprofloxacin and long-term prevention of spontaneous bacterial peritonitis: results of a prospective controlled trial.

The aim of this prospective double-blind study was to evaluate the value of long-term antibiotic prophylaxis using ciprofloxacin for the prevention of spontaneous bacterial peritonitis (SBP) in 60 cirrhotic patients with low ascitic fluid protein levels (< 15 g/L). The patients were assigned to two groups: group I (n = 28) ciprofloxacin 750 mg per os once a week for 6 months, group II (n = 32) placebo. The two groups were similar for clinical and laboratory characteristics. Twelve patients developed an intercurrent disorder, and 10 patients died during the trial. There were no adverse effects in the treated group. There was a significant decrease in the incidence of SBP (3.6 vs. 22%) (P < .05) and duration of hospitalization (9.3 +/- 4.5 vs. 17.6 +/- 6.2 days) (P < .05) in the treated group as compared with the placebo group. The bacteriological study showed no acquired resistance to ciprofloxacin after 6 months' treatment. These results suggest that long-term preventive antibiotic prophylaxis based on the weekly administration of 750 mg of ciprofloxacin is effective in the prevention of SBP in cirrhotic patients.

Adult↗
PubMed1995

p53 protein accumulation in oesophageal squamous cell carcinomas and precancerous lesions.

AIMS: To investigate the immunohistochemical expression of p53 protein in oesophageal squamous cell carcinomas and in dysplastic areas of the oesophageal mucosa surrounding the tumours. METHODS: Biopsy samples were obtained from 20 patients with an oesophageal squamous cell carcinoma. Blocks of the tumours and of the surrounding mucosa were immunostained with the monoclonal antibody DO-7. RESULTS: Fourteen of the 20 carcinomas were positive for p53 (70%). The frequency of p53 overexpression increased with the differentiation of the tumour. Nine out of 13 dysplastic specimens were positive for p53 (69%): eight cases with severe dysplasia and one case with moderate dysplasia. No p53 immunostaining was detected in normal oesophageal epithelium. All p53 positive dysplastic specimens were taken from the mucosa adjacent to tumours that were also immunostained. In moderate dysplastic mucosa the p53 positive cells were located in the proliferative basal zone, whereas in severe dysplasia the immunostained cells increased in number and spread to upper cell layers of the epithelium. CONCLUSION: This study supports the hypothesis that TP53 gene is frequently involved in the development of oesophageal squamous cell carcinoma and that p53 protein accumulation is an early event in human oesophageal carcinogenesis.

Adult↗