Ulcerative Colitis: Modigliani R

Modigliani R. · Department of Hepatogastroenterology, Saint Louis Hospital, 1 Avenue Claude Vellefaux, 75475 Paris, Cedex 10, France. · Inflamm Bowel Dis. · Pubmed #11854611 No free full text.

This publication has no abstract.

Modigliani R. · Gastroentérologie, Hôpital Saint-Louis, Paris. · Gastroenterol Clin Biol. · Pubmed #10897789 No free full text.

This publication has no abstract.

Gornet JM, Couve S, Hassani Z, Delchier JC, Marteau P, Cosnes J, Bouhnik Y, Dupas JL, Modigliani R, Taillard F, Lemann M. · Department of Gastroenterology, Hôpital Saint-Louis, Paris, France. · Aliment Pharmacol Ther. · Pubmed #12869077 links to  free full text

Abstract: BACKGROUND: The efficacy of infliximab in ulcerative colitis (UC) and indeterminate colitis has been poorly assessed and preliminary results are conflicting. METHODS: The records of 30 patients treated with infliximab for ulcerative colitis (n=19) or indeterminate colitis (n=11) were reviewed. Infliximab was given because of steroid resistance (n=18), dependence (n=5) or intolerance (n=7); five patients had failed on cyclosporin; 19 patients had a severe flare-up. RESULTS: Median duration of follow-up was 10 months. In 28 patients with active disease, the response rate was 75% at day 7, with 43% having a complete remission, and 50% at month 1, with 32% having a complete remission. Among the 22 responders, the probability of relapse was 73% at month 6. The probability of complete remission without steroids, taking into account the re-treatment for relapse (n=11), was 57% (95% confidence interval (CI): 45% to 69%) at month 6. The probability of colectomy was 33% (95% CI: 23% to 43%) at month 12. In indeterminate colitis, response rate was only 50% at day 7 and 30% at month 1. Concomitant use of antimetabolite agents was associated with better results. CONCLUSIONS: Infliximab was able to induce a rapid response in some patients with UC or indeterminate colitis refractory to conventional treatment. Long-term results were less favourable, with frequent relapses, and about one-third of the patients required a colectomy.

Allez M, Modigliani R. · Hôpital St-Louis, Paris, France. · Curr Opin Gastroenterol. · Pubmed #17031097 No free full text.

Abstract: The purpose of this review is to highlight new developments during the past year regarding diagnosis and clinical features of inflammatory bowel disease. Endoscopy remains the cornerstone for diagnosis and evaluation of ileocolonic inflammatory bowel disease. In ulcerative colitis, recent studies have challenged the concept of a continuous and homogeneous inflammatory process with constant rectal involvement: patchy inflammation and rectal sparing were reported in treated ulcerative colitis, and frequent cecum and appendiceal orifice skip lesions were confirmed. Cross-sectional imaging techniques usefully complement endoscopy by assessing whole-bowel thickness and detecting abscesses and fistulae. Furthermore, echo Doppler ultrasound is able to measure mesenteric blood flow, which is increased in active inflammatory bowel disease and seems to parallel inflammatory disease activity. Osteopenia, which affects approximately half of patients with inflammatory bowel disease, can be detected by dual-energy x-ray absorptiometry and prevented. Hyperhomocysteinemia, a predisposing factor for thrombosis, seems to be more frequent in inflammatory bowel disease, and can be corrected by folate supplementation. The concept of an aggressive, penetrating form of Crohn disease with early postoperative recurrence as opposed to a more indolent, nonpenetrating form of the disease, with later recurrence, was recently challenged. The most significant predictor of the risk of malignancy in inflammatory bowel disease remains the presence of dysplasia in colonic biopsy specimens. A dysplastic polypoid lesion or mass is a strong predictor of cancer but should be distinguished from the dysplasia inherent in a coincident sporadic adenoma.

Zouali H, Lesage S, Merlin F, Cézard JP, Colombel JF, Belaiche J, Almer S, Tysk C, O'Morain C, Gassull M, Christensen S, Finkel Y, Modigliani R, Gower-Rousseau C, Macry J, Chamaillard M, Thomas G, Hugot JP, Anonymous00017, Anonymous00018. · Fondation Jean Dausset-CEPH, Paris, France. · Gut. · Pubmed #12477763 links to  free full text

Abstract: BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD. PATIENTS AND METHODS: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test. RESULTS: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence. CONCLUSION: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.

Lesage S, Zouali H, Cézard JP, Colombel JF, Belaiche J, Almer S, Tysk C, O'Morain C, Gassull M, Binder V, Finkel Y, Modigliani R, Gower-Rousseau C, Macry J, Merlin F, Chamaillard M, Jannot AS, Thomas G, Hugot JP, Anonymous00210, Anonymous00211, Anonymous00212. · Fondation Jean Dausset-CEPH, 27 rue Juliette Dodu, 75010 Paris, France. · Am J Hum Genet. · Pubmed #11875755 links to  free full text

Abstract: CARD15/NOD2 encodes a protein involved in bacterial recognition by monocytes. Mutations in CARD15 have recently been found in patients with Crohn disease (CD), a chronic inflammatory condition of the digestive tract. Here, we report the mutational analyses of CARD15 in 453 patients with CD, including 166 sporadic and 287 familial cases, 159 patients with ulcerative colitis (UC), and 103 healthy control subjects. Of 67 sequence variations identified, 9 had an allele frequency >5% in patients with CD. Six of them were considered to be polymorphisms, and three (R702W, G908R, and 1007fs) were confirmed to be independently associated with susceptibility to CD. Also considered as potential disease-causing mutations (DCMs) were 27 rare additional mutations. The three main variants (R702W, G908R, and 1007fs) represented 32%, 18%, and 31%, respectively, of the total CD mutations, whereas the total of the 27 rare mutations represented 19% of DCMs. Altogether, 93% of the mutations were located in the distal third of the gene. No mutations were found to be associated with UC. In contrast, 50% of patients with CD carried at least one DCM, including 17% who had a double mutation. This observation confirmed the gene-dosage effect in CD. The patients with double-dose mutations were characterized by a younger age at onset (16.9 years vs. 19.8 years; P=.01), a more frequent stricturing phenotype (53% vs. 28%; P=.00003; odds ratio 2.92), and a less frequent colonic involvement (43% vs. 62%; P=.003; odds ratio 0.44) than were seen in those patients who had no mutation. The severity of the disease and extraintestinal manifestations were not different for any of the CARD15 genotypes. The proportion of familial and sporadic cases and the proportion of patients with smoking habits were similar in the groups of patients with CD with or without mutation. These findings provide tools for a DNA-based test of susceptibility and for genetic counseling in inflammatory bowel disease.

Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G. · Fondation Jean Dausset CEPH, 27 rue J. Dodu 75010 Paris, France. · Nature. · Pubmed #11385576 No free full text.

Abstract: Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.