PubMed Health⌕ Search

Biomedical subjects

Frank Zerbib

Publications and source records attributed to Frank Zerbib.

At least 19 recordsLinked to original sources
PubMed2007

Multidrug resistance gene-1 polymorphisms and resistance to cyclosporine A in patients with steroid resistant ulcerative colitis.

BACKGROUND: Cyclosporine A (CsA) is inconstantly effective in inducing remission in acute attacks of ulcerative colitis (UC) not responding to steroids. This study aimed to establish whether multidrug resistance gene (MDR)1 polymorphisms would be associated with CsA failure. PATIENTS AND METHODS: The distribution of the different genotypes of single nucleotide polymorphisms (SNP) G2677T/A and C3435T of MDR1 exons 21 and 26, respectively, was studied in 154 patients (mean age, 44 yr) who had received CsA to treat severe attacks of steroid resistant UC in 11 centers in France and Belgium. Patients were classified as CsA failure (n = 50) when they needed colectomy within 30 days after CsA initiation. The SNPs were detected by use of a 5' nuclease allelic discrimination assay. RESULTS: There was a significant association between the G2677T/A polymorphism distribution (exon 21) and the risk for CsA failure (P = 0.0001). The TT genotype of exon 21 was significantly associated with the risk compared with the two other genotypes (odds ratio, 3.77; 95% confidence interval, 1.42-9.97, P = 0.007). There was no significant association between the genotype C3435T distribution (exon 26) and the risk of CsA failure (P = 0.23). CONCLUSION: The TT genotype of exon 21 MDR1 polymorphisms is associated with a higher risk of CsA failure in patients with steroid resistant UC. Further studies should be performed to establish whether other treatments could be more efficient to avoid surgery in this subset of patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Effect of rebamipide on the colonic barrier in interleukin-10-deficient mice.

Our aim was to study the effect of a mucosal protective agent, rebamipide, on the colonic barrier and the immune response in colitis-prone interleukin-10-deficient (IL-10-/-) C57BL/6 mice infected with Helicobacter hepaticus. After sacrifice, in all mice, control, or previously infected with H. hepaticus, or previously infected and treated with rebamipide enema, a histological examination of colonic samples was performed, intestinal permeability was studied in Ussing chamber, and mesenteric lymph node proliferation and cytokine secretion were measured. Mice treated with rebamipide presented a reinforcement of the distal colonic epithelial barrier, an increase of mesenteric lymph node cells proliferation, and of IFNgamma and IL-12 secretion. These results indicate that in IL-10-/- mice with mild colitis, rectally administered rebamipide reinforces the distal colonic barrier and has a slight Th1 immuno-stimulatory effect on mesenteric lymph node cells. These properties could be helpful in the management of some inflammatory bowel diseases.

Alanine↗
PubMed2006

Two-dimensional blue native/SDS gel electrophoresis of multiprotein complexes from Helicobacter pylori.

The study of protein interactions constitutes an important domain to understand the physiology and pathogenesis of microorganisms. The two-dimensional blue native/SDS-PAGE was initially reported to analyze membrane protein complexes. In this study, both cytoplasmic and membrane complexes of a bacterium, the strain J99 of the gastric pathogen Helicobacter pylori, were analyzed by this method. It was possible to identify 34 different proteins grouped in 13 multiprotein complexes, 11 from the cytoplasm and two from the membrane, either previously reported partially or totally in the literature. Besides complexes involved in H. pylori physiology, this method allowed the description of interactions involving known pathogenic factors such as (i) urease with the heat shock protein GroEL or with the putative ketol-acid reductoisomerase IlvC and (ii) the cag pathogenicity island CagA protein with the DNA gyrase GyrA as well as insight on the partners of TsaA, a peroxide reductase/stress-dependent molecular chaperone. The two-dimensional blue native/SDS-PAGE combined with mass spectrometry is a potential tool to study the differences in complexes isolated in various situations and also to study the interactions between bacterial and eucaryotic cell proteins.

Antigens, Bacterial↗
PubMed2006

Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy.

INTRODUCTION: Combined esophageal pH-impedance monitoring allows detection of nearly all gastroesophageal reflux episodes, acid as well as nonacid. However, the role of nonacid reflux in the pathogenesis of symptoms is poorly known. The aim of this study was to evaluate the diagnostic yield of this technique in patients with suspected reflux symptoms while on or off PPI therapy. PATIENTS AND METHODS: The recordings of 150 patients recruited at seven academic centers with symptoms possibly related to gastroesophageal reflux were analyzed. Reflux events were detected visually using impedance (Sandhill, CO) and then characterized by pHmetry as acid or nonacid reflux. The temporal relationship between symptoms and reflux episodes was analyzed: a symptom association probability (SAP) > or =95% was considered indicative of a positive association. RESULTS: One hundred fifty patients were included, 102 women (mean age 52 +/- 14 yr, range 16-84). Among the 79 patients off PPI, five did not report any symptom during the recording period. A positive SAP was found in 41 of the 74 symptomatic patients (55.4%), including acid reflux in 23 (31.1%), nonacid reflux in three (4.1%), and acid and nonacid in 15 (20.3%). In the group of patients on PPI (N = 71, 46 women, mean age 51 +/- 15 yr), 11 were asymptomatic during the study, SAP was positive in 22 of the 60 symptomatic patients (36.7%), including acid reflux in three (5.0%), nonacid reflux in 10 (16.7%), and acid and nonacid in nine (15.0%). The symptoms most frequently associated with nonacid reflux were regurgitation and cough. CONCLUSION: Adding impedance to pH monitoring improves the diagnostic yield and allows better symptom analysis than pHmetry alone, mainly in patients on PPI therapy. The impact of this improved diagnostic value on gastroesophageal reflux disease management remains to be investigated by outcome studies.

Adolescent↗
PubMed2006

Peptic ulcer disease in a patient with ankylosing spondylitis receiving a conventional nonsteroidal anti-inflammatory drug.

BACKGROUND: A 42-year-old man with a 10-year history of HLA-B27-positive ankylosing spondylitis presented with upper abdominal pain and nausea after receiving oral ketoprofen 200 mg/day. His gastrointestinal symptoms did not improve with the addition of ranitidine 150 mg twice daily. He had previously responded well to conventional nonsteroidal anti-inflammatory drugs. INVESTIGATIONS: Physical examination, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, radiography, laboratory tests, upper gastrointestinal endoscopy, histopathologic examination and culture of biopsy specimens. DIAGNOSIS: Helicobacter pylori-positive duodenal ulcer. TREATMENT: For eradication of H. pylori: omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily for 1 week. For ankylosing spondylitis: diclofenac 150 mg/day in combination with omeprazole 20 mg/day for 2 months.

Adult↗
PubMed2006

Repeated pneumatic dilations as long-term maintenance therapy for esophageal achalasia.

INTRODUCTION: In esophageal achalasia, pneumatic dilations (PD) provide short-term and long-term remission rates of 60-90% and 40-50%, respectively. The aim of this study was to evaluate the long-term efficacy of repeated PD as long-term maintenance therapy. PATIENTS AND METHODS: From 1992 to 2004, 150 patients with esophageal achalasia treated by PD were included in this retrospective study (78 males, mean age 57 +/- 20 yr). PD were performed until remission was achieved (symptom score < or = 3, each item < 2) and subsequently when symptomatic recurrence occurred. A standardized symptoms questionnaire was sent to patients lost to follow-up. Results are expressed as mean +/- SD. RESULTS: Initial remission was achieved in 137 of 150 (91.3%) patients with 2.67 +/- 1.59 dilations [range 1-12]. Failure and perforation rates were 7.3% (n = 11) and 1.3% (n = 2), respectively. After initial remission, 48 of 137 (35%) patients had recurrent symptoms; the probability to be in remission at 5 and 10 yr was 67% and 50%, respectively. At the end of follow-up (45 +/- 38 months, ext. 2-144) 108 of 137 (78.8%) patients were in remission. Among 112 patients whose symptoms could be treated by repeated PD (per protocol analysis), 108 (96.4%) were in remission (3.5 +/- 2.1 PD, ext. 2-12). In this group, the probability of being in remission after repeated PD at 5 and 10 yr was 96.8% and 93.4%, respectively. No pretherapeutic factor influenced long-term remission rate. The overall prevalence of gastroesophageal reflux was 34.7%. CONCLUSION: One-third of the patients with esophageal achalasia treated by PD will experience symptomatic recurrence during a 4-yr period. Long-term remission can be achieved in virtually all the patients treated by repeated PD according to an "on-demand" strategy based on symptom recurrence.

Adolescent↗
PubMed2005

Predictors of response to infliximab in luminal Crohn's disease.

AIMS: To identify predictive factors of response to infliximab in luminal Crohn's disease (CD). PATIENTS AND METHODS: All consecutive patients with luminal CD treated with infliximab between October 1999 and March 2003 in Bordeaux's referral centers were included. All had at least 3 months follow-up post infliximab infusion and no prior treatment with infliximab. Response rates were determined 2 and 8 weeks after infusion according to Crohn's Disease Activity Index (CDAI) (remission=CDAI<150 and response=CDAI decrease more than 100). RESULTS: Among 44 patients (33 female; mean age 35 +/- 14 yr.), 39 (88%) had a clinical response 2 weeks after infusion (79% in remission). At week 8, the rate of response was 61.4% and exclusive colonic involvement predicted sustained response to treatment (P=0.03). The probability of remission at 56 weeks was 21.4%. Multivariate analysis demonstrated that the only factor associated with response duration was initiating immunosuppressive (IS) therapy in women (RR=3.61 95%CI[1.25-10.41], P=0.017). CONCLUSION: Exclusive colonic involvement is the only predictive factor of sustained response to infliximab in luminal CD. At the time of infliximab infusion, initiation or modification of IS therapy may favor sustained response, at least in women.

Adult↗
PubMed2005

Efficacy of intravenous cyclosporin in moderately severe ulcerative colitis refractory to steroids.

OBJECTIVE: The efficacy of intravenous cyclosporin (CSA) in acute severe ulcerative colitis (UC) is well established. The aim of this study was to evaluate its efficacy in moderately severe colitis refractory to steroids. METHODS: Twenty-six patients (17 men, mean age 41 +/- 14 yr) with UC refractory to steroids treated with CSA were included in this study. Severity was defined according to Truelove criteria. A clinical activity score below 10 during 2 consecutive days defined clinical response. RESULTS: According to Truelove criteria, all patients had moderate UC. CSA was administered IV at a mean daily dose of 3.7 +/- 0,5 mg/kg until response and then orally for 3.5 +/- 2.6 months. A clinical response was achieved in 20/26 patients (76,9%) within 5.7 +/- 2.8 days (5/6 failures were treated by proctocolectomy). During a follow-up of 27.8 +/- 20.8 months, relapse rate was 60% (12/20): 7 patients underwent proctocolectomy and 5 had clinical remission with CSA retreatment (N=4) and steroids (N=1). At the end of follow-up, 12 patients (46%) were in clinical remission, 12 (46%) required colectomy, 1 had chronic active UC and 1 was lost of follow-up. The probability to avoid surgery was 52% at 78 months. The only factor associated with avoidance of surgery was concomitant treatment with azathioprine (P=0.007). Ten reversible adverse events occurred in 9 patients. CONCLUSION: This study shows that CSA is safe and effective in moderately severe steroid resistant UC. Concomitant treatment with azathioprine significantly decreases the rate of subsequent surgery. CSA may act as a "bridge" until the therapeutic action of azathioprine is achieved for maintenance treatment. These results should be further confirmed by a prospective controlled study.

Administration, Oral↗
PubMed2005

Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal rule.

OBJECTIVE: To assess oncologic outcome of patients treated by conservative radical surgery for tumors below 5 cm from the anal verge. SUMMARY BACKGROUND DATA: Standard surgical treatment of low rectal cancer below 5 cm from the anal verge is abdominoperineal resection. METHODS: From 1990 to 2003, patients with a nonfixed rectal carcinoma at 4.5 cm or less from the anal verge and without external sphincter infiltration underwent conservative surgery. Surgery included total mesorectal excision with intersphincteric resection, that is, removal of the internal sphincter, to achieve adequate distal margin. Patients with T3 disease or internal sphincter infiltration received preoperative radiotherapy. RESULTS: Ninety-two patients with a tumor at 3 (range 1.5-4.5) cm from the anal verge underwent conservative surgery. There was no mortality and morbidity was 27%. The rate of complete microscopic resection (R0) was 89%, with 98% negative distal margin and 89% negative circumferential margin. In 58 patients with a follow-up of more than 24 months, the rate of local recurrence was 2% and the 5-year overall and disease-free survival were 81% and 70%, respectively. CONCLUSIONS: The technique of intersphincteric resection permits us to achieve conservative surgery in patients with a tumor close to or in the anal canal without compromising local control and survival. Tumor distance from the anal verge is no longer a limit for sphincter-saving resection.

Adult↗
PubMed2005

Evaluation of the homologous recombination in Helicobacter pylori.

BACKGROUND: Most strategies for direct mutagenesis of Helicobacter pylori primarily involve genomic DNA cloning which is a time-consuming and expensive technique. METHODS: To make a gene replacement, we propose a strategy using polymerase chain reaction (PCR) amplicons to allow a double homologous recombination in the genome of H. pylori. Different strains were used to validate this strategy and we describe how the amplicon insertion was made with accuracy. Moreover, we looked for the shortest homologous sequence needed to allow a specific gene replacement in H. pylori without any deletion, insertion or mutation at the recombination site. All of the experiments were performed at the flaA locus, whose gene encodes the major flagellin. RESULTS: Amplicons bearing 500 or 150 bp flanking regions of flaA on each side (depending on the strain) were sufficient to allow the specific insertion of a 1173 bp chloramphenicol cassette into the genome of H. pylori. The insertion was accurate with no substitutions at the insertion locus. CONCLUSIONS: This information opens the door to other strategies for mutagenesis used for the identification of virulence factors without deleting genes, which would not be based on a negative screening system. For example, they could be useful in performing protein fusion for a better understanding of the virulence factor's mechanism.

Alleles↗
PubMed2005

Bifidobacterium breve and Streptococcus thermophilus secretion products enhance T helper 1 immune response and intestinal barrier in mice.

Lactic acid bacteria or their secretion products can modulate immune responses differently in normal and inflammatory conditions. This comparative study analyzes the effect of oral administration of living lactic acid bacteria, or their conditioned media, on the epithelial and immune functions of colitis-prone C57BL/6 IL-10-deficient mice. Mice were untreated (control) or infected with Helicobacter hepaticus with or without oral treatment with living bacteria, Bifidobacterium breve C50 and Streptococcus thermophilus 065 (LB), or their culture-conditioned media (CM). Histology, cytokine mRNA, electrical resistance, and barrier capacity of colonic samples as well as cytokine secretion by mesenteric lymph node (MLN) cells were studied. Helicobacter hepaticus mice developed only mild colitis, which was not modified in LB or CM groups. In the CM (but not the LB) group, the colonic barrier was reinforced as compared to the other groups, as evidenced by decreased horseradish peroxidase (HRP) transcytosis and mannitol fluxes and increased electrical resistance. In MLN, the percentage of CD4+ and CD8+ T cells secreting IFNgamma was significantly higher in CM (2.06% and 1.98%, respectively) mice than in H. hepaticus (1.1% and 0.47%, P < 0.05) or control mice. In addition, the nonspecific stimulation of IFNgamma, TNFalpha, and IL-12 secretion by MLN cells was significantly higher in the CM group as compared to the other groups. In the absence of severe colitis, Bifidobacterium breve C50- and Streptococcus thermophilus 065-conditioned media can reinforce intestinal barrier capacity and stimulate Th1 immune response, highlighting the involvement of lactic acid bacteria-derived components in host defense.

Animals↗
PubMed2004

Comparison of functional results and quality of life between intersphincteric resection and conventional coloanal anastomosis for low rectal cancer.

PURPOSE: The technique of intersphincteric resection permits sphincter preservation with good oncologic results in very low rectal cancer. This study aimed to investigate functional results and quality of life after intersphincteric resection compared with conventional coloanal anastomoses. METHODS: From 1990 to 2000, 170 patients underwent total mesorectal excision with coloanal anastomosis for low rectal tumors. Questionnaires were obtained from 77 patients alive without colostomy: 37 had a conventional coloanal anastomosis and 40 had intersphincteric resection. Both groups were similar according to age, gender, anastomotic stenosis, colonic pouch, anastomotic leakage, preoperative radiotherapy, and follow-up (median, 56 months). Assessment included one functional and two quality-of-life questionnaires: the SF-36 Health Status and the Fecal Incontinence Quality of Life score. RESULTS: There was no difference in stool frequency, fragmentation, urgency, dyschesia, and alimentary restriction between patients with and without intersphincteric resection. Patients with intersphincteric resection had significantly worse continence (Wexner score, 10.8 vs. 6.9; P < 0.001) and needed more antidiarrheal drugs (60 vs. 35 percent; P = 0.04) than those without. Compared with conventional coloanal anastomoses, quality of life was altered by intersphincteric resection for the subscale embarrassment ( P < 0.01) in the Fecal Incontinence Quality of Life score, whereas no difference of quality of life was observed with SF-36. CONCLUSIONS: Compared with conventional coloanal anastomoses, patients with intersphincteric resection have a higher risk of fecal incontinence and a slightly altered quality of life.

Adult↗
PubMed2004

Long-term functional results after sphincter-saving resection for rectal cancer.

INTRODUCTION: A number of patients suffer from gastrointestinal side effects following sphincter-saving resection of the rectum. The aim of this study was to assess frequency and risk factors of long-term gastrointestinal side effects after sphincter-saving resection for rectal cancer. PATIENTS AND METHODS: Between 1980 and 1997, among 209 patients treated for rectal cancer by rectal resection and sphincter conservation, 145 who were alive without recurrence or colostomy, responded to a questionnaire. There were 85 males and 60 females with a mean age of 64 Years; the follow-up was 5.4 Years. The functional result was considered good if the number of stools per 24h was three or less with normal continence and poor if the number of stools was four or more or if fecal incontinence was present. Influence of age, gender, anastomotic height, type of sutured colon, colonic pouch, defunctioning stoma, leakage, stenosis, radiotherapy, history of irritable bowel syndrome and follow-up were analyzed. RESULTS: The mean anastomotic height was 5 cm from the anal margin. Functional results were good in 56% of patients and poor in 44%. Univariate analysis showed three variables to be significantly associated with the functional results: anastomotic height (P=0.001), radiotherapy (P=0.03) and follow-up > 24 Months (P=0.009). Multivariate analysis showed that only anastomotic height independently influenced functional results. They were good in 76%, 53% and 35% of patients for anastomoses located above 6 cm, between 6 and 3 cm, and below 3 cm from the anal margin, respectively. CONCLUSION: After sphincter-saving resection for rectal cancer, about half of patients have poor long-term functional results, the latter being related only to the anastomotic height. This suggests the need to preserve a small part of the rectum when oncologically feasible.

Adult↗
PubMed2004

[Treatment of NSAIDs related dyspepsia].

NSAIDs-induced dyspepsia occurs in 10 to 30% of patients treated with NSAIDs, leading to discontinuation of treatment in 5 to 15%. Gastrointestinal tolerability of COX-2 selective inhibitors is better than for non-selective NSAIDs. Helicobacter pylori infection does not influence gastrointestinal tolerability of NSAIDs. Therefore, patients should not be tested and treated for H. pylori infection unless they have a history of peptic ulcer. Symptoms of NSAIDs-induced dyspepsia are poorly correlated with gastroduodenal mucosal damage. Therefore, upper gastrointestinal endoscopy should be performed only if symptom relief is not achieved with the first line empirical treatment and/or if symptoms suggestive of complications, such as bleeding, develop. Proton pump inhibitors appear to be the treatment of choice for NSAIDs-induced dyspepsia.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Evaluation of the association of nine Helicobacter pylori virulence factors with strains involved in low-grade gastric mucosa-associated lymphoid tissue lymphoma.

Helicobacter pylori has been associated with the development of two malignant diseases: gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although the cag pathogenicity island, especially the cagA gene, has been linked with adenocarcinoma, few data concerning H. pylori pathogenic factors involved in low-grade gastric MALT lymphoma are available. The goal of this study was to analyze the prevalence of and correlation between genes coding for seven H. pylori virulence factors (cagA, cagE, vacA, iceA, babA, hopQ, and oipA) and two novel adhesins (sabA and hopZ) by comparing a collection of 43 H. pylori strains isolated from patients with low-grade gastric MALT lymphoma to 39 strains isolated from age-matched patients with gastritis only. Our results show that taken individually, none of the nine genes tested can be considered associated with MALT strains and allow us to conclude that MALT pathogenesis is not linked with more proinflammatory H. pylori strains. We demonstrated that in patients infected with strains harboring the iceA1 allele, sabA functional status, and hopZ "off" status, the odds of developing a MALT lymphoma were 10 times higher. However, the low prevalence of such strains (10 of 43 MALT strains) renders this triple association a low-sensitivity marker for MALT strains. Our data confirmed that H. pylori virulence factors are correlated with one another. If the involvement of H. pylori in MALT lymphoma is well established, the pathomechanism by which gastric lymphoma occurs remains to be identified.

Adult↗
PubMed2003

[Does H. pylori infection or its eradication play a role in gastroeosphageal reflux disease?].

The relationships between Helicobacter pylori (H. pylori)and gastroesophageal reflux disease (GERD) remain controversial. Epidemiological studies do not support an important role of H. pylori in the pathogenesis of GERD although some studies showing a low prevalence of the infection in GERD patients suggest that it could protect against the development of either symptoms or esophagitis. This hypothesis has been reinforced by the increased prevalence of esophagitis following H. pylori eradication in duodenal ulcer patients, although conflicting results have been reported. An increased gastric acid secretion following H. pylori eradication in patients who previously had corpus gastritis may explain this phenomenon. H. pylori eradication does not exacerbate GERD symptoms and may, in some cases, improve them. H. pylori-associated gastritis enhances the efficacy of antisecretory drugs as evidenced by the lower gastric pH values after eradication; however, as far as healing rates and symptom relief are concerned, the differences are probably not clinically relevant. Long term treatment with proton pump inhibitors could accelerate the development of atrophic gastritis, and therefore increase the risk of gastric cancer. However, conflicting results have been reported, so that further studies are needed before considering eradication of H. pylori systematically before long-term medical treatment for GERD.

Anti-Ulcer Agents↗