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Biomedical subjects

P Seksik

Publications and source records attributed to P Seksik.

13 recordsLinked to original sources

Review article: the role of bacteria in onset and perpetuation of inflammatory bowel disease.

We review the evidence that strongly suggests a role of the intestinal microbiota in the onset and perpetuation of inflammatory bowel disease (IBD). Experimental studies consisted of suppressing micro-organisms from the microbiota (using germ-free or gnotoxenic animals or antibiotics), introducing new micro-organisms or microbial components (e.g. probiotics, CpG-DNA) or selectively increasing some endogenous bacteria (e.g. using prebiotics). Intervention studies were performed in patients or animal models of spontaneous or chemically-induced colitis. Information was also obtained from observational studies that described the composition of the faecal and mucosal microbiota at various stages of the disease process and in controls. Many have used culture-independent techniques that identify bacteria based on the nucleic acid sequence of ribosomal RNA molecules. Microbiota in patients with IBD seem to be characterized by high concentrations of bacteria in contact with the mucosa, instability, the presence of high numbers of unusual bacteria and sometimes a reduction in the biodiversity. Studies searching for a generalized or localized dysbiosis in IBD are discussed, as well as those trying to identify bacterial molecules and receptors, which may be implicated in triggering the inflammatory process.

Bacterial Infections↗

Temperature gradient gel electrophoresis of fecal 16S rRNA reveals active Escherichia coli in the microbiota of patients with ulcerative colitis.

Previous studies of the endogenous microbiota in patients with ulcerative colitis (UC) have not taken bacterial activity into account, yet bacteria with high transcriptional activity might have a more important pathophysiological role than inactive bacteria. We therefore analyzed the biodiversity of active bacteria in the fecal microbiota of UC patients, in comparison with that of healthy subjects. Feces were collected from nine patients with active UC and from nine healthy controls. Total DNA and RNA were extracted, and 16S ribosomal DNA and RNA were amplified by PCR and reverse transcription-PCR, respectively. Amplification products were compared by means of temporal temperature gradient gel electrophoresis (TTGE). Bands of interest were excised, sequenced, and identified by comparison with the GenBank database (NCBI). The dominant-species diversity based on RNA-derived TTGE profiles was significantly lower for UC patients than for healthy controls (P = 0.01). The mean similarity index between the "present" and "active" microbiota was 74% +/- 18% for UC patients. Comparison of the individual "active" microbiota identified a band that was present for eight UC patients and only two controls (89% versus 22%; P = 0.008). The band was sequenced for 6 patients and always corresponded to Escherichia coli. The biodiversity of active bacteria in the dominant fecal microbiota of patients with UC is lower than that of healthy subjects. E. coli is more represented in the active microbiota of UC patients. The possible pathophysiological role of this difference remains to be determined.

Adult↗

Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn's disease: a randomised, double blind, placebo controlled GETAID trial.

BACKGROUND AND AIMS: Early endoscopic recurrence is frequent after intestinal resection for Crohn's disease. Bacteria are involved, and probiotics may modulate immune responses to the intestinal flora. Here we tested the probiotic strain Lactobacillus johnsonii LA1 in this setting. PATIENTS AND METHODS: This was a randomised, double blind, placebo controlled study. Patients were eligible if they had undergone surgical resection of <1 m, removing all macroscopic lesions within the past 21 days. Patients were randomised to receive two packets per day of lyophilised LA1 (2 x 10(9) cfu) or placebo for six months; no other treatment was allowed. The primary endpoint was endoscopic recurrence at six months, with grade >1 in Rutgeerts' classification or an adapted classification for colonic lesions. Endoscopic score was the maximal grade of ileal and colonic lesions. Analyses were performed primarily on an intent to treat basis. RESULTS: Ninety eight patients were enrolled (48 in the LA1 group). At six months, endoscopic recurrence was observed in 30/47 patients (64%) in the placebo group and in 21/43 (49%) in the LA1 group (p = 0.15). Per protocol analysis confirmed this result. Endoscopic score distribution did not differ significantly between the LA1 and placebo groups. There were four clinical recurrences in the LA1 group and three in the placebo group. CONCLUSION: L johnsonii LA1 (4 x 10(9) cfu/day) did not have a sufficient effect, if any, to prevent endoscopic recurrence of Crohn's disease.

Adult↗

Video capsule endoscopy for investigation of obscure gastrointestinal bleeding: feasibility, results, and interobserver agreement.

BACKGROUND AND STUDY AIMS: The aim of the study was to assess the feasibility, diagnostic yield, and interobserver agreement of capsule endoscopy in the investigation of patients with obscure or occult gastrointestinal bleeding. PATIENTS AND METHODS: A total of 64 consecutive patients with occult bleeding (31 %) or overt bleeding (69 %) were assessed using capsule endoscopy after negative upper and lower endoscopy and small-bowel radiology. The quality of visualization of the small-bowel mucosa was scored from 1 (poor) to 4 (excellent). Thirty video capsule recordings with normal or abnormal findings were blindly assessed by four independent endoscopists. Interobserver agreement was evaluated using the kappa index. RESULTS: The small bowel was completely visualized in 57/64 patients (89 %). Incomplete small-bowel transit was most commonly due to prolonged gastric retention (five patients). The mucosa visualization scores (means) for the proximal, middle, and distal thirds of the small bowel were 3.7, 3.3, and 2.2 respectively. Visualization of the distal ileum was good (> or = 3) in 38 % and a bleeding site was found in 45 % of patients. Push-enteroscopy was also performed in 56 patients. The results of the two techniques were similar in 37 patients, capsule endoscopy was superior in 12 patients, and push-enteroscopy was superior in seven patients. Interobserver agreement was good for bleeding and for angiodysplasia, but poor for ulcers and tumors. Mean interobserver agreement was better among experienced endoscopists than among junior endoscopists. CONCLUSIONS: Capsule endoscopy allowed the whole small intestine to be explored in 89 % of patients, with good visualization of the mucosa, except distally. Interobserver agreement was better among the experienced endoscopists and was better for red-colored abnormalities (bleeding and angiodysplasia) than for ulcers and tumors.

Adult↗

Inflammatory bowel disease: what is new?

This article reviews a selection of 50 papers on inflammatory bowel disease published between April 2002 and August 2003. The new information and progress summarized here includes: the role of bacteria, their interaction with CARD15/NOD2 gene products and the modulating effects of probiotics; new imaging techniques, such as wireless capsule endoscopy and chromoendoscopy for detecting dysplasia, and fecal markers. It has not been possible to review every aspect of treatment, and the focus here is on factors capable of predicting the efficacy and tolerance of infliximab and new treatments, including natalizumab, thalidomide, cyclophosphamide and 6-thioguanine.

Antibodies, Monoclonal↗

Review article: gut flora and inflammatory bowel disease.

The pathogenesis of inflammatory bowel disease involves interactions between the host susceptibility, mucosal immunity and intestinal microflora. There is therefore great interest in the changes in the endogenous flora in inflammatory bowel disease patients and in the establishment of potential genetic variations in host responses to endogenous bacteria. In this review, we summarize the modifications in the various regional ecosystems in the gastrointestinal tract during inflammatory bowel disease (luminal bacteria in faeces or inside the gastrointestinal tract, bacteria in mucus and bacteria directly attached to the mucosa). Results were obtained following a 'candidate microorganism strategy' and, as is occurring increasingly frequently, following a 'full description strategy', which has progressed largely due to the development of culture-independent techniques. The possibility of modifying the ecosystem using prebiotics or probiotics offers hope for new treatment developments, particularly in the prevention of relapse.

Bacteria↗

Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon.

BACKGROUND AND AIMS: The colonic microflora is involved in the pathogenesis of Crohn's disease (CD) but less than 30% of the microflora can be cultured. We investigated potential differences in the faecal microflora between patients with colonic CD in remission (n=9), patients with active colonic CD (n=8), and healthy volunteers (n=16) using culture independent techniques. METHODS: Quantitative dot blot hybridisation with six radiolabelled 16S ribosomal ribonucleic acid (rRNA) targeting oligonucleotide probes was used to measure the proportions of rRNA corresponding to each phylogenetic group. Temporal temperature gradient gel electrophoresis (TTGE) of 16S rDNA was used to evaluate dominant species diversity. RESULTS: Enterobacteria were significantly increased in active and quiescent CD. Probe additivity was significantly lower in patients (65 (11)% and 69 (6)% in active CD and quiescent CD) than in healthy controls (99 (7)%). TTGE profiles varied markedly between active and quiescent CD but were stable in healthy conditions. CONCLUSION: The biodiversity of the microflora remains high in patients with CD. Enterobacteria were observed significantly more frequently in CD than in health, and more than 30% of the dominant flora belonged to yet undefined phylogenetic groups.

Adolescent↗

Probiotics and intestinal health effects: a clinical perspective.

Probiotics are viable non-pathogenic micro-organisms which, when ingested, exert a positive influence on host health or physiology. We have critically analysed the evidence for the efficacy of specific probiotic strains in human gastrointestinal diseases. The best evidence can be obtained with randomised controlled trials which avoid bias. Good evidence has been obtained with several strains in the prevention or treatment of antibiotic-associated disorders, in the treatment (and to a lesser extent prevention) of gastroenteritis and acute diarrhoea and in the alleviation of lactose intolerance. We also analysed the recent randomised controlled trials performed in patients with Clostridium difficile or Helicobacter pylori, inflammatory bowel disease, irritable bowel syndrome, non-ulcer dyspepsia and colon cancer.

Anti-Bacterial Agents↗

Comparison of the faecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis.

OBJECTIVES: To determine whether differences within the complex intestinal microflora can be demonstrated between patients with ankylosing spondylitis (AS) and healthy individuals. METHODS: The composition of the faecal microflora of 15 ankylosing spondylitis patients and 15 matched controls was determined using a variety of nucleic acid-based methods, including denaturing gradient gel electrophoresis (DGGE). Concentrations of serum antibodies reactive with intestinal bacteria were determined. T-cell proliferation responses to autologous intestinal bacteria were determined using a bioluminescent assay. RESULTS: DGGE demonstrated a unique and stable bacterial community in the faeces of each individual. No specific differences in colonization profiles were discernible between patients and controls. Analysis of individual bacterial groups using nucleic acid-based methods showed no differences in faecal colonization with Klebsiella pneumoniae or Bacteroides vulgatus. A significantly higher proportion of faecal samples from AS patients were found to contain sulphate-reducing bacteria compared with samples from controls (P=0.0004). Three out of five patients showed elevated T-cell proliferation responses to Bacteroides species cultured from their own faeces. The concentrations of serum immunoglobulin A (IgA) and IgM antibodies reactive with klebsiella or bacteroides cells were lower in the patient group relative to the controls. CONCLUSIONS: By using DGGE, we have demonstrated the complexity and individuality of the human intestinal microflora and shown that this is a confounding factor in determining the possible significance of individual organisms in the pathogenesis of spondyloarthritis. Nevertheless, we demonstrated a higher prevalence of sulphate-reducing bacteria in the faeces of patients with AS. These organisms have been implicated in the pathogenesis of inflammatory bowel disease. We also detected a possible loss of immunological tolerance to autologous Bacteroides isolates in patients with AS.

Bacteroides↗

Fatal herpetic hepatitis in adult following short corticotherapy: a case report.

Herpes simplex virus hepatitis (HSV hepatitis) is an uncommon and severe complication of HSV type 1 and HSV type 2 infection. HSV hepatitis affects mostly immunocompromised patients. We report the case of a young man without any previous known immunodeficiency who developed fatal HSV hepatitis in the first 8 days of oral corticotherapy given for ulcerative colitis. A prompt diagnosis was possible because HSV was recovered from peripheral blood leukocytes.

Acute Disease↗

[Efficacity of treatment with lamivudine in two patients with severe reactivation of hepatitis B after withdrawal of chemotherapy].

Reactivation of chronic infection is a serious complication during and especially after the withdrawal of cancer chemotherapy in hepatitis B virus carriers. Mortality is high, ranging from 4 to 20%. We report two cases of severe reactivation, after withdrawal of chemotherapy for chronic lymphocytic leukemia in one case and for a bladder tumor in the other. Recovery occurred with lamivudine therapy. Morbidity and mortality are common in these cases, especially when intensive chemotherapy and/or chronic hepatitis and/or precore mutants viruses are involved. Although lamivudine seems to be effective in these cases, prophylactic use has not been clearly defined and must be evaluated.

Aged↗