Ulcerative Colitis: Galmiche JP

Message L, Bourreille A, Laharie D, Quinton A, Galmiche JP, Lamouliatte H, Alamdari A, Zerbib F. · Service d'Hépato-gastroentérologie, Hôpital Saint-André, Bordeaux. · Gastroenterol Clin Biol. · Pubmed #15864171 links to  free full text

Abstract: 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.

Maunoury V, Savoye G, Bourreille A, Bouhnik Y, Jarry M, Sacher-Huvelin S, Ben Soussan E, Lerebours E, Galmiche JP, Colombel JF. · Gastroenterology Department, University Hospital, Lille, France. · Inflamm Bowel Dis. · Pubmed #17206697 links to  free full text

Abstract: BACKGROUND: Wireless capsule endoscopy (WCE) can identify small bowel mucosal lesions not seen with other imaging modalities. This technique can therefore play an important diagnostic role in the evaluation of patients with inflammatory bowel disease type unclassified (IBDU). We report on a multicentric study whose objective was to evaluate the value of WCE to increase diagnostic accuracy in categorizing IBDU. METHODS: Thirty patients with IBDU and negative serology were included. WCE was performed with a standard Pillcam capsule. Outcome measures were classified as suggestive of Crohn's disease (CD) when -3 ulcerations were present. RESULTS: WCE displayed endoscopic features suggestive for CD in 5 patients. In 6 other patients, WCE was negative, but repeated ileocolonoscopy with biopsies performed during follow-up evaluation revealed CD in 5 and ulcerative colitis (UC) in 1 patient. UC was found in a seventh case at colectomy performed just after WCE. Eighteen patients remained with a diagnosis of IBDU 16 months on average after WCE. CONCLUSIONS: WCE is a potentially clinically useful technique for categorizing a subgroup of patients with IBDU, although negative WCE does not exclude further diagnosis of CD. Patients with negative WCE who remain IBDU at follow-up evaluation may belong to an original subgroup of IBD.

Barbier M, Vidal H, Desreumaux P, Dubuquoy L, Bourreille A, Colombel JF, Cherbut C, Galmiche JP. · Pôle Digestif et CIC-INSERM, CHU Nantes et INRA, 44093 Nantes Cedex 1. · Gastroenterol Clin Biol. · Pubmed #14732844 links to  free full text

Abstract: BACKGROUND: Leptin, a protein with a cytokine-like structure, is produced predominantly by adipocytes. It appears to play a key role in immune responses by increasing the secretion of Th1 and pro-inflammatory cytokines. As fat-wrapping is a characteristic feature of Crohn's disease (CD), and as increased leptin levels have been reported in animal models of intestinal inflammation, this study investigated whether mesenteric adipose tissue could be a source of leptin in human inflammatory bowel disease (IBD). AIM: To quantify the expression of leptin mRNA in mesenteric adipose tissue of patients with CD or ulcerative colitis (UC). METHODS: Specimens were obtained from mesenteric white adipose tissue close to healthy and inflammatory small intestine and/or colon in patients with CD or UC and, for controls, from apparently healthy mesentery of patients operated for carcinoma of the right colon. The expression of leptin mRNA was assessed by reverse transcription-competitive polymerase chain reaction. RESULTS: Leptin mRNA levels were significantly higher in mesenteric adipose tissue of CD and UC patients than in controls (P<0.05). In CD and UC, concentrations were not significantly different in mesenteric fat specimens, whether contiguous to macroscopically normal or grossly abnormal intestine. CONCLUSIONS: This study provides the first evidence of a novel abnormality of the mesentery of patients with IBD. Overexpression of leptin mRNA in mesenteric adipose tissue may contribute to (a) the inflammatory process, (b) enhancement of mesenteric TNF alpha expression in CD (as recently reported), and/or (c) the anorexia frequently reported during flares of IBD.

Neunlist M, Aubert P, Toquet C, Oreshkova T, Barouk J, Lehur PA, Schemann M, Galmiche JP. · INSERM U 539, Place Alexis Ricordeau, Nantes, France. · Gut. · Pubmed #12477766 links to  free full text

Abstract: BACKGROUND: Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel diseases but it is still uncertain whether neurochemical coding of myenteric neurones is altered in ulcerative colitis (UC). AIMS: In this study we investigated transmitter co-localisation in myenteric neurones of normal colon and the colon of patients with UC. METHODS: Choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal peptide (VIP), and substance P (SP) were detected by immunohistochemical methods in whole mounts of colonic myenteric plexus of UC patients (n=10) and controls (n=8). RESULTS: The proportion of ChAT positive and VIP positive neurones relative to the NSE population did not differ in inflamed (33.3% and 9.3%, respectively) and non-inflamed segments (33.6% and 9.7%) of UC colon compared with controls (35.0% and 6.9%). The proportion of SP positive neurones was significantly larger in both inflamed (15.5%) and non-inflamed (20.3%) segments than in controls (5.9%). Analysis of changes in subpopulations showed that 26.9% of neurones were only ChAT positive in controls but that the proportion was significantly smaller in inflamed (18.8%) and non-inflamed (15.8%) areas of UC. The proportions of neurones containing ChAT and SP were significantly higher in inflamed (11.8%) and non-inflamed (13.9%) areas than in controls (5.0%). CONCLUSION: Remodelling of myenteric neurones in UC involves a shift from mainly cholinergic to more SP positive innervation. This effect may constitute part of the neuronal basis for the motility disturbances observed in UC.

Taddei C, Audrain MA, Reumaux D, Sesboüe R, Testa A, Galmiche JP, Duthilleul P, Colombel JF, Esnault VL. · Department of Nephrology-Clinical Immunology, Hôtel Dieu, Nantes, France. · Eur J Gastroenterol Hepatol. · Pubmed #10563543 No free full text.

Abstract: OBJECTIVES: Alpha1-antitrypsin (alpha1-AT) is encoded by a highly polymorphic gene with over 75 codominantly expressed alleles at the protease inhibitor (Pi) locus classified as normal, deficient, dysfunctional or null. The aim of this study was to determine in patients with inflammatory bowel disease: (i) the prevalence of anti-neutrophil cytoplasmic auto-antibodies (ANCA) and their antigen specificities; (ii) alpha1-AT Pi phenotypes; and (iii) possible associations between ANCA, disease activity and deficient alpha1-AT alleles. DESIGN: Study of 95 consecutive patients with ulcerative colitis (UC) and 63 patients with Crohn's disease (CD). METHODS: Diagnosis and disease activity were determined by clinical, endoscopic and histological criteria. ANCA by indirect immunofluorescence (IIF) and Pi phenotyping by isoelectric focusing were performed for all patients. Positive IIF sera were tested in antigen-specific enzyme-linked immunosorbent assay: proteinase 3 (PR3), myeloperoxidase (MPO), lactoferrin (LF), lysozyme, human leucocyte elastase (HLE), cathepsin G and bactericidal/permeability increasing protein (BPI). RESULTS: Sixty-one patients with UC (64.2%) and only 11 with CD (17.5%) had ANCA (P < 0.001). Antigen specificities were PR3 (7/61), MPO (3/61), LF (6/61), HLE (1/63) and BPI (10/61) in UC, and PR3 (2/11) and BPI (2/11) in CD. Three PiZ alleles were found, matching the prevalence in the normal French control population. No relationship was found between the presence of ANCA, antibody specificity, disease activity and deficient alpha1-AT alleles. CONCLUSION: ANCA are more frequent in UC than CD and do not correlate with disease activity. ANCA and protease/antiprotease imbalance do not appear to modulate the clinical course of inflammatory bowel disease.

Aube AC, Cherbut C, Barbier M, Xing JH, Roze C, Galmiche JP. · Centre de Recherche en Nutrition Humaine, Nantes, France. · Neurogastroenterol Motil. · Pubmed #10087535 No free full text.

Abstract: Changes in gastric emptying and orocaecal transit time in patients with ulcerative colitis suggest that disturbances in gut motility may not be restricted to inflamed sites. This study sought to characterize changes in the motility of noninflamed ileum in a rat colitis model and to explore the mechanism(s) potentially involved. The myoelectrical activity of the ileum was recorded in rats with trinitrobenzene sulphonic acid (TNBS)-induced colitis. The degree of ileal and colonic inflammation was assessed by quantification of macroscopic damage and myeloperoxidase activity (MPO). The effect on ileal motility of pretreatment with atropine, indomethacin and NG-nitro-L-arginine-methyl ester (L-NAME) was investigated. TNBS-induced inflammation was restricted to the distal colon, as evidenced by morphological scores and MPO. Colitis was associated with increased frequency of ileal migrating motor complexes, characterized mainly by a decrease in the duration of phases I and III. The occurrence of ileal giant migrating complexes remained unchanged. The myoelectrical changes observed in the ileum persisted after treatment with atropine, indomethacin and L-NAME. Distal colitis is associated with abnormal myoelectrical activity in the noninflamed ileum of rats. Neither acetylcholine nor prostaglandins and nitric oxide seem to be involved.