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Jean-Frédéric Colombel

Publications and source records attributed to Jean-Frédéric Colombel.

At least 19 recordsLinked to original sources
PubMed2006

Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors.

Abdominal pain is common in the general population and, in patients with irritable bowel syndrome, is attributed to visceral hypersensitivity. We found that oral administration of specific Lactobacillus strains induced the expression of mu-opioid and cannabinoid receptors in intestinal epithelial cells, and mediated analgesic functions in the gut-similar to the effects of morphine. These results suggest that the microbiology of the intestinal tract influences our visceral perception, and suggest new approaches for the treatment of abdominal pain and irritable bowel syndrome.

Abdominal Pain↗
PubMed2006

No evidence for an involvement of the p38 and JNK mitogen-activated protein in inflammatory bowel diseases.

Involvement of mitogen-activated protein (MAPK) in inflammatory bowel disease (IBD) remains enigmatic. We sought to evaluate the expression and activity of p38 and JNK MAPK in IBD and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and the effects of a p38 inhibitor, SB203580, in TNBS colitis. P38 and JNK were quantified in colonic mucosa of 28 IBD patients and 19 controls and in 77 TNBS or control mice treated or not with SB203580. Colitis severity was assessed by survival, macroscopic and microscopic scoring, and molecular markers. Expression and activity of p38 and JNK were similar in IBD patients and controls and not modified by inflammation. In mice, p38 and JNK expression or activity did not increase following the induction of colitis. SB203580 decreased the p38 activity but displayed no clinical nor biological therapeutic effect. In conclusion, these results minimize the role of p38 and JNK in inflammatory colitis and the interest of p38 as a therapeutic target in IBD.

Adult↗
PubMed2006

Colectomy with ileorectal anastomosis preserves female fertility in ulcerative colitis.

OBJECTIVES: Restorative proctocolectomy with ileoanal anastomosis (IPAA) is the surgical standard for patients with ulcerative colitis (UC). Significant reduction in female fertility and fecundity after IPAA has been shown in recent studies. In selected cases, colectomy with ileorectal anastomosis (IRA) is another surgical option. The aim of this study was to evaluate fertility in women with UC who underwent IRA. PATIENTS AND METHODS: This study included all women with UC who underwent IRA between 1962 and 1999 and who were 40 years old or younger at the time of surgery, and older than 18 years of age at the time of the interview. Data were collected using a structured telephone interview concerning reproductive behavior and waiting times to pregnancy. RESULTS: Among 40 eligible patients, 37 whose mean age at IRA was 28 years (range 11-39) answered the questionnaire. Twenty-two were unmarried, not wishful of pregnancy and/or already had children. Among 15 females wishing children after IRA, 10 (66%) became pregnant: one had therapeutic abortion, two had a miscarriage, four had 1 child, two had 2 children and one had 4 children. Five patients were sterile after IRA. CONCLUSION: These preliminary results suggest that IRA for UC preserves female fertility. If confirmed in other series this information should be provided to young women with UC before deciding surgical option.

Adult↗
PubMed2006

Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibody markers of Crohn's disease.

BACKGROUND AND AIMS: Antibodies directed against oligomannose sequences alpha-1,3 Man (alpha-1,2 Man alpha-1,2 Man)(n) (n = 1 or 2), termed anti-Saccharomyces cerevisiae antibodies (ASCAs) are markers of Crohn's disease (CD). S. cerevisiae mannan, which expresses these haptens, is used to detect ASCA, but the exact immunogen for ASCA is unknown. Structural and genetic studies have shown that Candida albicans produces mannosyltransferase enzymes that can synthesize S cerevisiae oligomannose sequences depending on growth conditions. This study investigated whether C. albicans could act as an immunogen for ASCA. METHODS: Sequential sera were collected from patients with CD, systemic candidiasis, and rabbits infected with C. albicans. Antibodies were purified by using chemically synthesized (Sigma) ASCA major epitopes. These affinity-purified antibodies and lectins were then used to analyze the expression of ASCA epitopes on molecular extracts and cell walls of C. albicans and S cerevisiae grown in various conditions. RESULTS: In humans and rabbits, generation of ASCA was shown to be associated with the generation of anti-C. albicans antibodies resulting specifically from infection. By using affinity-purified antibodies, C. albicans was shown to express ASCA epitopes on mannoproteins similar to those of S. cerevisiae. By changing the growth conditions, C. albicans mannan was also able to mimic S. cerevisiae mannan in its ability to detect ASCA associated with CD. This overexpression of ASCA epitopes was achieved when C. albicans grew in human tissues. CONCLUSIONS: C. albicans is one of several immunogens for ASCA and may be at the origin of an aberrant immune response in CD.

Adult↗
PubMed2006

Polymorphism in IgG Fc receptor gene FCGR3A and response to infliximab in Crohn's disease: a subanalysis of the ACCENT I study.

Recently, it has been shown that FCGR3A-158 gene polymorphism is associated with biological and possibly clinical response to infliximab in Crohn's disease. We further assessed this association in a subset of 344 patients from the large and well-defined cohort of 573 patients with Crohn's disease from the ACCENT I study. No association could be observed between FCGR3A-158 gene polymorphism and the clinical response to infliximab, which was primarily defined as a decrease of >or=70 points in the Crohn's disease activity index or clinical remission (Crohn's disease activity index <150). We did, however, confirm a trend towards a greater decrease in C-reactive protein after infliximab in V/V homozygotes as compared with V/F heterozygotes and F/F homozygotes (-79.4, -76.5, and -64.3%, respectively, at week 6; P=0.085; one-tailed P=0.043). This finding has no immediate clinical impact but may enhance the understanding of the complex mechanisms of action of anti-tumor necrosis factor agents in Crohn's disease.

Adolescent↗
PubMed2006

A simple biological score for predicting low risk of short-term relapse in Crohn's disease.

BACKGROUND: In Crohn's disease, studies have evaluated the ability of biological markers to predict relapse in the next 12 to 18 months, without differentiating early from late relapses. The aim of this study was to look for biological markers of short-term relapse. MATERIALS AND METHODS: In a previous therapeutic trial, patients with a medically induced clinical remission had biological markers evaluated and updated every 6 weeks. A Cox model with time-dependent covariates was used for analysis. RESULTS: Among the 71 patients, 38 had a relapse. Multivariate analysis selected 2 markers predictive of relapse: C-reactive protein >20 mg/L and erythrocyte sedimentation rate >15 mm. A binary biological predictive score was derived: "negative" when both were lower than their limits, "positive" when otherwise. The relative risk of short-term relapse for patients with a positive score compared to those with a negative score was 8.0 (95% confidence interval 2.8-22.9). Sensitivity of the score was 89% and specificity was 43%. Assuming a 10% relapse rate every 6 weeks, negative and positive predictive values were 97% and 15%, respectively. CONCLUSIONS: This simple biological score can predict short-term maintenance of remission in Crohn's disease and may help physicians in the follow-up of patients in clinical remission.

Adult↗
PubMed2005

[Epidemiology and risk factors of inflammatory bowel diseases].

Inflammatory bowel diseases (IBD) are a public health problem in developed countries as 1 per 1000 people suffers from these diseases. Most of affected people are young adults. The incidence of IBD has increased considerably in western countries since the Second World War and it is beginning to level off. On the other hand, incidence is still rising in low incidence areas such as Eastern Europe, Asia and developing countries. Differences in incidence across age, time, and geographic areas suggest that environmental factors are acting in IBD but so far cigarette smoking and appendectomy are the only risk factors which have been consistently demonstrated. An important role for genetic factors in IBD was first suggested by epidemiological studies showing familial aggregation of IBD and by twin studies. In 2001, the first CD susceptibility gene, NOD2/CARD15 on chromosome 16, has been characterized. Other susceptibility genes have been localized. Their identification should help to understand the complex interaction between the environment and the intestinal immune system from which IBD are originating.

Age Distribution↗
PubMed2005

A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine.

BACKGROUND & AIMS: An open study reported that patients with Crohn's disease in remission who have taken azathioprine for longer than 3.5 years are at low risk of relapse when azathioprine is discontinued. To confirm this observation, we performed a multicenter, double-blind, noninferiority withdrawal study. METHODS: Patients who were in clinical remission on azathioprine for > or = 42 months were randomized to continue azathioprine or to receive an equivalent placebo for 18 months. The primary end point was clinical relapse at 18 months. RESULTS: Forty patients were randomly assigned to receive azathioprine and 43 to receive placebo. Characteristics of patients at entry were similar in the 2 study groups. At 18 months, 3 patients had a relapse in the azathioprine group, and 9 had a relapse in the placebo group. Kaplan-Meier estimates of the relapse rate at 18 months were 8% +/- 4% and 21% +/- 6%, respectively. The hypothesis that placebo was inferior to azathioprine was not rejected (P = .195). Among the baseline variables, C-reactive protein level > 20 mg/L, time without steroids < 50 months, and hemoglobin level < 12 g/dL were found to be predictive of relapse in the multivariate analysis. CONCLUSIONS: This study shows that azathioprine withdrawal is not equivalent to continued therapy with azathioprine for maintenance of remission in patients with Crohn's disease who have been in remission on azathioprine for > or = 3.5 years. Thus, azathioprine maintenance therapy should be continued beyond 3.5 years.

Adult↗
PubMed2005

Environmental factors in familial Crohn's disease in Belgium.

BACKGROUND: Environmental factors are believed to trigger the onset of Crohn's disease (CD) in genetically susceptible individuals. The aim of this study was to assess environmental and familial factors that might be etiologically related to CD. METHODS: Twenty-one families with 3 or more affected first-degree relatives were studied, together with 10 matched control families. There were 74 patients with CD, 84 unaffected family members, and 59 controls. Family members were interviewed together at the parental home. A 176-item questionnaire delved into first symptoms, childhood vaccinations and diseases, food items, potable water supplies, social activities, travel, pets, and home and surrounding environment. Questions were directed specifically for 2 time-frames, childhood until age 20 and a 10-year epoch before the onset of first symptoms within a family. The possible factors linked to disease were evaluated using univariate and multivariate logistic regression. RESULTS: There were significantly more smokers in the patients and their relatives than in controls. Patients had more appendicitis during adolescence, ate less oats, rye, and bran than controls, and consumed more unpasteurized cheese. Patients drank significantly less tap water and more well water than controls. Clustering of cases in time occurred in 13 of the 21 affected families. CONCLUSIONS: The less frequent consumption of oats, rye, and bran and the more frequent eating of unpasteurized cheeses imitate potential dietary influences on gastrointestinal flora. More importantly, our data suggest that the drinking of well water represents an important risk factor for CD.

Adolescent↗
PubMed2005

Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988-1999).

OBJECTIVE: To assess the incidence and location at diagnosis of inflammatory bowel disease in children and adolescents in northern France between 1988 and 1999. METHODS: A 12-year prospective population-based study was conducted by gastroenterologists and pediatric gastroenterologists of northern France (1,312,141 children <17 years of age). RESULTS: From 1988 to 1999, 509 cases of childhood inflammatory bowel disease were recorded (7.2% of all inflammatory bowel disease cases in Northern France): 367 Crohn disease, 122 ulcerative colitis and 20 indeterminate colitis. The mean standardized incidence was 3.1/10(5) for inflammatory bowel disease as a whole (2.3 for Crohn disease, 0.8 for ulcerative colitis and 0.12 for indeterminate colitis). Crohn disease location at diagnosis was: small bowel and colon (71%), colon only (10%) and small bowel only (19%). Location of initial ulcerative colitis was: proctitis (11%), left colitis (57%) and pancolitis (32%). Although ulcerative colitis incidence remained stable (0.8), Crohn disease incidence increased from 2.1 in 1988 to 1990 to 2.6 in 1997 to 1999 (P = 0.2). CONCLUSIONS: The incidence of Crohn disease in the children of northern France showed an increasing trend (20%; not significant) during the 12-year period while the incidence of ulcerative colitis remained stable. In the entire population(children and adults)the incidence of Crohn disease increased significantly (+23%; P < 0.001), while the incidence of ulcerative colitis decreased (-17%; P < 0.0001).

Adolescent↗
PubMed2005

Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology.

The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

Biomarkers↗
PubMed2004

Human CYP4F12 genetic polymorphism: identification and functional characterization of seven variant allozymes.

The human cytochrome CYP4F12 has been shown to be metabolically active toward inflammatory mediators and exogenous compounds such as antihistaminic drugs. We recently identified a genetic polymorphism within the promoter region, associated with a decreased level of enzyme expression. In the present study, we report the further identification of single nucleotide polymorphisms in the coding sequence of the CYP4F12 gene. A polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis of DNA samples from 53 unrelated French Caucasians, allowed the identification of ten mutations, comprising seven missense mutations, 31C>T (Leu11Phe), 38C>T (Pro13Leu), 47C>T (Met16Thr), 4759G>A (Asp76Asn), 4801G>A (Val90Leu), 8896C>T (Arg188Cys) and 23545G>A (Gly522Ser). Their functional impact toward ebastine hydroxylation was evaluated using heterologous expression in Saccharomyces cerevisiae cells of site-directed mutated cDNA variants. Five out seven variants did not exhibit any significant difference in CYP4F12 catalytic activity, whereas two variants, Val90Ile and Arg188Cys, displayed significant changes in their Michaelis-Menten (Km, Vm) parameters. These data on CYP4F12 genetic polymorphism provide tools for further studies of association with pathological processes involving an inflammatory component and with variations in anti-histaminic drug response.

Aryl Hydrocarbon Hydroxylases↗
PubMed2004

Impact of Small Bowel Exploration Using Video-Capsule Endoscopy in the Management of Acute Gastrointestinal Graft-versus-Host Disease.

BACKGROUND: The purpose of this study was to evaluate the impact of the global diagnostic approach on the outcome of patients suspected of having acute (a) gastrointestinal (GI) graft-versus-host disease (GVHD). METHODS: Ten consecutive patients with suspected aGI-GVHD were prospectively explored with an exhaustive approach including video-capsule endoscopy (VCE). Images observed with VCE were compared with results obtained with other GI investigations including duodenal biopsies. RESULTS.: Five patients had a normal VCE examination: four were successfully treated symptomatically, but one died as a result of toxoplasmosis. VCE disclosed aGI-GVHD lesions in all five remaining patients, and two of the five were considered normal by upper GI endoscopy. All of these patients experienced improvement in their GI symptoms within 2 weeks of adjustments to their immunosuppressive treatment. CONCLUSIONS: This approach has enhanced the authors' ability to adapt immunosuppressive treatments in patients suffering from suspected aGI-GVHD. Further investigation of the apparently high negative predictive value of VCE will be of great interest, particularly with a view to avoiding unnecessary immunosuppressive treatment.

Acute Disease↗