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Biomedical subjects

Y Bouhnik

Publications and source records attributed to Y Bouhnik.

At least 55 records · Page 3Linked to original sources

[6-mercaptopurine levels and study of blood lymphocyte subsets during azathioprine treatment of Crohn's disease].

OBJECTIVES: Our aim was to study the relationships between clinical efficacy of azathioprine, 6-mercaptopurine pharmacokinetics and changes in peripheral blood lymphocyte subpopulations induced by azathioprine treatment in Crohn's disease. METHODS: Twenty-three patients were prospectively followed up for 1 year. Peripheral blood counts, total lymphocytes, CD3+, CD4+, CD8+, CD25+, CD16+CD56+, CD57+ and CD19+ lymphocyte subpopulations were carried out, using flow cytometry, during azathioprine treatment. Pharmacokinetic studies were performed at day 8 and month 3 by measuring 6-mercaptopurine plasma concentration after an oral dose of azathioprine (2 mg/kg). Results were compared in responders (no activity and no steroids) and non-responders. RESULTS: The decrease in peripheral blood leukocytes and neutrophils was significant after 1 month, reaching 49% and 48% of the pre-treatment values at 1 year; the one of lymphocytes was significant after 6 months and reached 41% at 1 year. Percentages of CD3+, CD4+, CD8+, CD57+, CD16+CD56+ and CD19+ lymphocytes remained unchanged whereas percentage of CD25+ lymphocytes increased from 10% to 28% (P < 0.01). There was a high inter and intraindividual variability of 6-mercaptopurine peak plasma concentration and area under the curve. No significant difference was found between responders (n = 14) and non responders (n = 7) for pharmacokinetic parameters and lymphocyte subpopulations; there was no correlation between lymphocyte subpopulation changes and 6-mercaptopurine pharmacokinetics. CONCLUSION: Monitoring of 6-mercaptopurine plasma concentration and blood lymphocyte subpopulations is of little value in Crohn's disease patients treated with azathioprine.

Adult↗

Chronic diarrhoea and diabetes mellitus: prevalence of small intestinal bacterial overgrowth.

The mechanisms of chronic diarrhoea, a frequent symptom in diabetes mellitus, are multifactorial and complex, although small intestinal bacterial overgrowth and autonomic neuropathy seem to play a major role. This study evaluated the prevalence of small intestinal bacterial overgrowth and the effects of antibiotic treatment in a population of diabetic patients with chronic diarrhoea (defined as > 3 stools/24 h, weight > 200 g/24 h, duration > 3 weeks). Small intestinal bacterial overgrowth syndrome was diagnosed by glucose-hydrogen breath testing (sensitivity: 78%, specificity: 89%). The characteristics of diarrhoea (duration, number of stools per day, and gastrointestinal symptoms) were noted. Autonomic neuropathy was assessed by cardiac parasympathetic tests. A total of 35 patients were included, 15 with small intestinal bacterial overgrowth syndrome (43%, group 1) and 20 with no bacterial overgrowth (group 2). Age (52.9 +/- 13.5 vs. 53.9 +/- 11.8 years, NS), duration of diabetes (13.8 +/- 9.1 vs. 10.6 +/- 7.8 years, NS), and HbA1c level (10 +/- 2.9 vs. 10.9 +/- 2.4%, NS) were not different between the two groups. In group 1, duration of diarrhoea was longer (18.1 +/- 18.5 vs. 7.75 +/- 4.02 months, P = 0.05), the number of stools higher (7.1 +/- 5.7 vs. 4.6 +/- 2.6/24 h, P < 0.05), and gastrointestinal symptoms more frequent (13 vs. 10, P < 0.05). The prevalence of small intestinal bacterial overgrowth syndrome and gastrointestinal symptoms was not different in patients with and without autonomic neuropathy (9 vs. 8 and 12 vs. 11 respectively, NS). Eight patients with bacterial overgrowth received antibiotics (amoxicillin-clavulanic acid, 1.5 g/24 h for 10 days). Dramatic clinical improvement was observed in 6 out of 8 of these patients. It is concluded that small intestinal bacterial overgrowth should be considered in case of chronic diabetic diarrhoea because of its frequency (43%), facility of diagnosis, and often successful treatment with antibiotics.

Bacteria↗

Administration of transgalacto-oligosaccharides increases fecal bifidobacteria and modifies colonic fermentation metabolism in healthy humans.

Transgalacto-oligosaccharides are a mixture of oligosaccharides consisting of glucose and galactose; they are not digested in the human small intestine. In vitro, they specifically stimulate the growth of bifidobacteria. The aim of the present work was to assess tolerance of transgalacto-oligosaccharides and the effects of their prolonged administration on bifidobacteria and fermentative activity of colonic flora. Eight healthy subjects were given 10 g of transgalacto-oligosaccharides per day for 21 d in two daily doses. A breath test and stool sample collection were carried out on d 1, 7, 14 and 21 of transgalacto-oligosaccharides ingestion. The stools of three subjects were collected and mixed before the study, and then inoculated in vitro into a fermentor to which 10 g transgalacto-oligosaccharides was added daily for 14 d. In the eight volunteers, administration of transgalacto-oligosaccharides led to a significant decrease in breath hydrogen excretion (P < 0.01) and a significant increase in fecal concentrations of bifidobacteria from (means +/- SEM) 8.6 +/- 0.6 to 9.7 +/- 0.5, 9.7 +/- 0.6 and 9.5 +/- 0.6 log colony-forming units (CFU)/g on d 1, 7, 14 and 21, respectively (P < 0.05). Fecal concentrations of enterobacteria, as well as stool weight, fecal water and pH did not change during the study. In vitro, transgalacto-oligosaccharides fermentation became more efficient and faster with time. In addition, metabolic alterations such as a rise in acetate proportion and lactate formation after 7 d of fermentation were observed, indicating the transformation of the inoculated fecal flora into an acid-resistant lactic flora. Prolonged administration of transgalacto-oligosaccharides, at a dose which does not induce digestive symptoms, increases the number of bifidobacteria and alters the fermentative activity of colonic flora in humans.

Adult↗

Primary ileal villous atrophy is often associated with microscopic colitis.

Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal malabsorption and/or efficacy of cholestyramine. Diagnosis is based on ileoscopy and histology. An association with microscopic colitis was present in the three patients and in four cases in the literature. The pathogenesis of primary ileal villous atrophy remains unknown and may involve dysimmunity. Its association with microscopic colitis may indicate a common pathogenesis or support the hypothesis that the faecal stream or bile salts play a role in the pathogenesis of microscopic colitis.

Adult↗

Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine.

BACKGROUND: Crohn's ulcerative gastrointestinal disease is presently managed through a variety of medical interventions, including-according to severity of illness-anti-inflammatory, immunosuppressive, and corticosteroid agents; and with remedial surgery to correct anatomical abnormalities caused by disease processes. The immunosuppressant azathioprine (or its metabolite, 6-mercaptopurine) is considered an efficient maintenance therapy for Crohn's, but there is always concern about bone-marrow suppression, liver damage, and other adverse effects. For how long persons with this disease should be given these drugs has not been determined. METHODS: Patients who were treated with azathioprine or 6-mercaptopurine for more than 6 months, and who were in prolonged clinical remission (> 6 months without steroids) were followed. The time-to-relapse was analysed in those on treatment, in those who stopped treatment for reasons other than a relapse, and in the whole sample, taking into account that they could be treated with the drugs or not, as a function of time. The influence of concomitant variables on time-to-relapse rate was examined using the Cox proportional hazard model. FINDINGS: In the 157 patients who continued to take the therapy, cumulative probabilities of relapse at 1 and 5 years were 11% and 32% respectively. Female gender, younger age, and a time for achieving remission more than 6 months were associated with a higher risk of relapse. In 42 patients who stopped therapy, probabilities of relapse at 1 and 5 years were 38% and 75%, respectively. Male gender, younger age and duration of remission less than 4 years were associated with a higher risk of relapse. After 4 years of remission on these drugs, the risk of relapse appeared to be similar, whether the therapy was maintained or stopped. INTERPRETATION: Taking into account the potential risks of long-term immunosuppressive therapy, the usefulness of maintaining azathioprine or 6-mercaptopurine in patients who have been in remission for more than 4 years is questionable.

Adolescent↗

Effects of fructo-oligosaccharides ingestion on fecal bifidobacteria and selected metabolic indexes of colon carcinogenesis in healthy humans.

Fructo-oligosaccharides (FOS) are a mixture of oligosaccharides consisting of glucose linked to fructose units. They are not digested in the human small intestine but fermented in the colon, where they could specifically promote the growth of some species of the indigenous microflora, especially bifidobacteria. We assessed in healthy humans the effects of FOS ingestion in fecal bifidobacteria and selected metabolic indexes potentially involved in colonic carcinogenesis. Twenty volunteers randomly divided into two groups were studied for three consecutive 12-day periods. During the ingestion period, they received 12.5 g/day FOS or placebo (saccharose) in three oral doses. Stools were regularly collected and analyzed. FOS ingestion led to an increase in fecal bifidobacterial counts [7.9 +/- 0.5 to 9.1 +/- 0.3 (SE) log colony-forming units/g wet wt, p < 0.01] and beta-fructosidase activity (9.6 +/- 1.9 to 13.8 +/- 1.9 IU/g dry wt, p < 0.01). In contrast, FOS ingestion had no significant effect on fecal total anaerobes, pH, the activities of nitroreductase, azoreductase, and beta-glucuronidase, and the concentrations of bile acids and neutral sterols. We conclude that ingestion of FOS, at a clinically tolerated dose of 12.5 g/day, led to an increase in colonic bifidobacteria. This effect was not associated in healthy humans with beneficial changes in various factors potentially involved in the pathogenesis of colonic cancer.

Adult↗

Antineutrophil cytoplasmic autoantibodies in autoimmune liver and inflammatory bowel diseases.

Perinuclear antineutrophil cytoplasmic autoantibodies have been described in inflammatory bowel diseases and in primary sclerosing cholangitis. Because the data concerning their occurrence are conflicting, we have used indirect immunofluorescence on ethanol-fixed neutrophils to test the sera from a large population of 382 patients with various liver and digestive diseases: in particular, from 27 patients with primary sclerosing cholangitis, 105 patients with autoimmune chronic active hepatitis, 30 patients with primary biliary cirrhosis and 124 patients with inflammatory bowel disease. The prevalence of the perinuclear antineutrophil cytoplasmic autoantibodies was 37% in ulcerative colitis and 15% in Crohn's disease. They would not be helpful in the differential diagnosis between these two inflammatory bowel diseases. Within the group of autoimmune liver diseases, perinuclear antineutrophil cytoplasmic autoantibodies were detected in 44% of sera from patients with primary sclerosing cholangitis and in 36% of sera from patients with type I autoimmune active hepatitis, but not in primary biliary cirrhosis. When primary sclerosing cholangitis was associated with an inflammatory bowel disease, the prevalence of these autoantibodies was 60%. They were 88% specific for primary sclerosing cholangitis and 86% specific for type I autoimmune active hepatitis. Despite their moderate sensitivity and specificity in primary sclerosing cholangitis, they remain the only serologic marker of this autoimmune liver disease. Moreover, they turned out to be a more sensitive marker for inflammatory bowel disease with associated primary sclerosing cholangitis.

Adolescent↗

Effects of Bifidobacterium sp fermented milk ingested with or without inulin on colonic bifidobacteria and enzymatic activities in healthy humans.

OBJECTIVE: To assess in healthy humans the effects of prolonged ingestion of Bifidobacterium sp fermented milk (BFM) with or without inulin on fecal bifidobacteria and some bacterial enzymatic activities. DESIGN: Twelve volunteers randomly divided into two groups were studied for three consecutive periods. During the ingestion period, they received BFM in association with ether 18g/d inulin or placebo in three oral doses for 12 days. Stools were regularly collected for bacteriological analysis. SETTING: Clinical Nutrition Unit, Hopital Saint-Lazare, Paris. RESULTS: The administration of BFM with placebo led to an increase in total bifidobacteria (indigenous and exogenous) (P < 0.01) and exogenous bifidobacteria (P < 0.01) and a decrease in beta-glucuronidase activity (P < 0.01). Simultaneous administration of BFM and inulin led to an increase in total bifidobacteria (P < 0.01) and exogenous bifidobacteria (P < 0.01), but had no effect on beta-glucuronidase activity. No differences were found for fecal concentrations reached by exogenous and indigenous bifidobacteria between the two groups. Administrated alone or with inulin, BFM did not change fecal total anaerobe counts, pH, nitrate reductase, nitroreductase and azoreductase activities. CONCLUSIONS: Administration of BFM substantially increases the proportion of bifidobacteria in the colonic flora, but the concurrent administration of inulin does not enhance this effect.

Adult↗

[Anti-endomysium and anti-reticulin antibodies in adults with celiac disease followed-up in the Paris area].

OBJECTIVES: Circulating IgA class anti-endomysium and anti-reticulin antibodies are reliable serological markers for the diagnosis of coeliac disease. The aim of this study was to evaluate their diagnostic sensitivity and specificity, and their prevalence in a group of coeliac adults taking a gluten-free diet followed in Ile-de-France. METHODS: One hundred and forty-five sera from 134 patients were examined for IgA and IgG anti-endomysium and anti-reticulin antibodies by indirect immunofluorescence. Sixty-eight patients were confirmed coeliacs; 8 patients with noncoeliac (unresponsive to a gluten-free diet) duodenal villous atrophy and 58 patients with no villous atrophy served as controls. RESULTS: In active coeliac disease, the sensitivity of anti-endomysium and anti-reticulin antibodies was 88% and 50%, respectively. Their specificity was 100%: they were never detected in case of noncoeliac villous atrophy. Under a strict gluten-free diet, their prevalence was 7% and 0%, respectively. CONCLUSION: In the studied population, the diagnosis accuracy of IgA anti-endomysium antibodies confirms their usefulness in screening and follow-up of coeliac disease. The absence of anti-endomysium and anti-reticulin antibodies in those cases with noncoeliac villous atrophy suggests that in the latter, different immunopathologic mechanisms, as compared with coeliac disease, are concerned.

Adolescent↗

[Peliosis hepatitis during intestinal lymphomatous polyposis treated with chemotherapy and radiotherapy. Regression after antibiotic therapy].

We report a case of regressive peliosis hepatis, which occurred in a 55 year-old woman with diffuse intestinal lymphomatous polyposis in remission after treatment with chemotherapy and radiotherapy, and which was cleared after one month treatment with erythromycin. The Warthin-Sarry stain, performed to identify a specific agent such as Rochalimaea quintana and henselae, was negative, and the polymerase chain reaction technique could not be performed. Regressive cases of peliosis hepatis are rare, and 4 out of 7 have been reported after antibiotic treatment. Two of them were observed after an antibiotic regimen with erythromycin in patients with HIV disease, and the bacilli Rochalimaea quintana and henselae were identified in liver tissue with Warthin-Starry stain and polymerase chain reaction technique. The observation and the regressive cases recently reported elsewhere, suggest that appropriate antibiotic treatment should be proposed when peliosis hepatis occurs.

Anti-Bacterial Agents↗

Identification of Bifidobacterium strains by rRNA gene restriction patterns.

Total DNA from 21 collection or industrial Bifidobacterium strains was cleaved with various restriction endonucleases. Following electrophoresis, the fragments were subjected to Southern blot hybridization with a heterologous [alpha-32P]dCTP-labeled rDNA (genes coding for rRNA) 23S gene probe. The ribosomal patterns allowed all tested strains to be differentiated and previous classifications to be confirmed. The same method was used to characterize DNA from 121 Bifidobacterium isolates collected from the intestinal flora of five human volunteers after the induction of colonic bacterial imbalance by antibiotics and absorption of a resistant exogenous Bifidobacterium strain. Hybridizations with the ribosomal probe revealed 11 different ribosomal patterns in addition to that of the exogenous strain. They permitted the Bifidobacterium populations belonging to the dominant colonic flora to be monitored over time. This experiment revealed significant and sustained alterations of the endogenous intestinal flora; indeed, some strains were eliminated, while others, probably belonging to subdominant flora, replaced them. Furthermore, even 2 months after the end of antibiotic treatment, the colonic flora remained different from that observed before treatment. Finally, our results showed that antibiotherapy did not allow colonic colonization by the exogenous strain.

Bacterial Typing Techniques↗