Clinical and radiological characteristics of lung disease in inflammatory bowel disease.
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The pulmonary associations of inflammatory bowel disease (IBD) are poorly characterized. The clinical, physiological and high-resolution computed tomographic thorax characteristics of the lung disease in patients with IBD presenting with respiratory symptoms are described. Detailed clinical information was obtained and standard pulmonary physiological tests and thorax high-resolution computed tomography performed on 14 patients with ulcerative colitis (UC) and three with Crohn's disease (CD), 10 male, aged 38-83 yrs. Respiratory symptoms had been present for 2-50 yrs and extraintestinal manifestations were present in three (17.6%). Normal pulmonary physiology (six patients) was associated with the high resolution computed tomographic changes of bronchiectasis, mosaic perfusion and air trapping suggestive of obliterative bronchiolitis and a pattern of centrilobular nodules and branching linear opacities ("tree in bud" appearance) suggestive of either cellular bronchiolitis or bronchiolectasis with mucoid secretions. Bronchiectasis was found in 13 patients (11 UC, 2 CD), 11 had air trapping and five had a "tree in bud" appearance on computed tomography. One patient had a predominantly peripheral reticular pattern at the lung bases similar to that found in cryptogenic fibrosing alveolitis and one patient had a mixed reticular and ground-glass pattern in the midzones with a patchy distribution in the central and peripheral portions of the lungs with air trapping. Eleven patients (three with alveolitis) exhibited a clinical and/or physiological response to steroids. Pulmonary abnormalities in ulcerative colitis and Crohn's disease can present years after the onset of the bowel disease and can affect any part of the lungs. Early recognition is important as they can be strikingly steroid-responsive. (+info)
Severe tracheobronchial stenosis in a patient with Crohn's disease.
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Tracheobronchial involvement in Crohn's disease is rare, usually associated with symptoms of tracheobronchitis, and typically responds well to steroids. The authors report a case of a 29-yr old patient with Crohn's disease, who presented with dyspnoea, fever, and a productive cough. Computed tomography of the chest revealed extensive nodular tracheobronchial stenosis, that was accompanied by severe mucosal inflammation at bronchoscopy. High-dose oral steroids diminished the mucosal inflammation, but had limited efficacy on the underlying tracheobronchial stenosis. It is speculated that this relative ineffectiveness of steroids may be due to the persistence of the untreated inflammatory process. (+info)
123I-interleukin-2 scintigraphy for in vivo assessment of intestinal mononuclear cell infiltration in Crohn's disease.
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Activated mononuclear cells expressing interleukin-2 (IL2) receptors (IL2-Rs) heavily infiltrate the Crohn's disease (CD) gut wall. A new technique for the in vivo detection of tissue infiltrating IL2-R positive (IL2R+ve) cells was developed based on 123I-IL2 scintigraphy. The aim of this study was to investigate whether 123I-IL2 accumulates in the CD gut wall in different phases of the disease and to evaluate the specificity of 123I-IL2 binding to activated IL2R+ve cells infiltrating the gut wall. METHODS: Fifteen patients with ileal CD (10 active and 5 inactive) and 10 healthy volunteers were studied by 123I-IL2 scintigraphy. Six patients with active CD were studied before and after 12 wk of steroid treatment. After scintigraphy, patients were followed up for 29-54 mo. Ex vivo autoradiography was performed to determine specificity of 125I-IL2 binding to IL2R+ve cells. For bowel scintigraphy, 123I-IL2 (75 MBq) was injected intravenously and gamma camera images were acquired after 1 h. Bowel radioactivity was quantified in 64 regions of interest (ROIs). RESULTS: Autoradiography showed specific binding of 125I-IL2 to IL2R+ve mononuclear cells infiltrating the CD gut wall. Intestinal 123I-IL2 uptake assessed by the number of positive ROIs was higher in patients with active or inactive CD than in healthy volunteers (P < 0.0001 and P = 0.03, respectively) and positively correlated with the CD activity index (P = 0.01). 123I-IL2 intestinal uptake significantly decreased in patients with CD in steroid-induced remission (P = 0.03). A significant correlation was observed between the number of positive ROIs and time to disease relapse. CONCLUSION: 123I-IL2 accumulates in the diseased CD gut wall by specific binding to IL2R+ve cells, infiltrating the involved tissues. 123I-IL2 scintigraphy may be an objective tool for the in vivo assessment of intestinal activated mononuclear cell infiltration. (+info)
Altered lipid profile, lipoprotein composition, and oxidant and antioxidant status in pediatric Crohn disease.
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BACKGROUND: Growing evidence supports a role for peroxidation in the pathogenesis of Crohn disease (CD). The activation of inflammatory cells, the release of their mediators, and the excessive production of free radicals may affect circulating lipids. OBJECTIVE: We examined the lipid profile, lipoprotein composition, and oxidant-antioxidant status of children with CD. DESIGN: We studied 22 pediatric CD patients and 10 healthy control subjects. RESULTS: The proportion of saturated and monounsaturated fatty acids in plasma of CD patients was higher but that of polyunsaturated fatty acids was lower than in control subjects. This resulted in higher ratios in CD patients of palmitoleic acid to linoleic acid (P < 0. 05) and of eicosatrienoic acid to arachidonic acid (P < 0.04), 2 established indexes of essential fatty acid deficiency. Hypocholesterolemia was noted in CD patients as a result of lower LDL-cholesterol concentrations than in control subjects (P < 0.02). Plasma apolipoproteins B (P < 0.02) and A-I (P < 0.02) were also lower in CD patients, whereas plasma triacylglycerols were higher (P < 0.005). Lipoprotein composition was altered in CD patients, with relative triacylglycerol depletion and protein enrichment in VLDL. In contrast, intermediate-density lipoprotein of CD patients was characterized by an increased percentage of triacylglycerol and protein (P < 0.005) and a reduced proportion of phospholipids (P < 0. 01). Additional abnormalities were observed in the chemical distribution of HDL(2) and HDL(3) moieties. Lipid peroxidation was documented by higher plasma malondialdehyde concentrations in CD patients (P < 0.05), accompanied by lower retinol concentrations (P < 0.02). CONCLUSION: Disturbances in the lipid profile, in lipoprotein concentrations and composition, and in oxidant-antioxidant status occur in CD patients. (+info)
Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa.
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Fractalkine is a unique chemokine that combines properties of both chemoattractants and adhesion molecules. Fractalkine mRNA expression has been observed in the intestine. However, the role of fractalkine in the healthy intestine and during inflammatory mucosal responses is not known. Studies were undertaken to determine the expression and function of fractalkine and the fractalkine receptor CX3CR1 in the human small intestinal mucosa. We identified intestinal epithelial cells as a novel source of fractalkine. The basal expression of fractalkine mRNA and protein in the intestinal epithelial cell line T-84 was under the control of the inflammatory mediator IL-1beta. Fractalkine was shed from intestinal epithelial cell surface upon stimulation with IL-1beta. Fractalkine localized with caveolin-1 in detergent-insoluble glycolipid-enriched membrane microdomains in T-84 cells. Cellular distribution of fractalkine was regulated during polarization of T-84 cells. A subpopulation of isolated human intestinal intraepithelial lymphocytes expressed the fractalkine receptor CX3CR1 and migrated specifically along fractalkine gradients after activation with IL-2. Immunohistochemistry demonstrated fractalkine expression in intestinal epithelial cells and endothelial cells in normal small intestine and in active Crohn's disease mucosa. Furthermore, fractalkine mRNA expression was significantly up-regulated in the intestine during active Crohn's disease. This study demonstrates that fractalkine-CX3CR1-mediated mechanism may direct lymphocyte chemoattraction and adhesion within the healthy and diseased human small intestinal mucosa. (+info)
New aspects of surgical therapy of recurrent Crohn's disease.
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Crohn's disease can neither be cured by surgery nor by medical therapy. Surgical therapy of recurrent Crohn's disease requires special precautions. The recurrence rate is 60% after 15 years. There are no certain data of the risk factors influencing the recurrence rate. The only clear facts are that wide resection out of the resection margins and smoking negatively influence recurrence. Hence, the major principles of therapy is a minimally-resected surgery. This mainly concerns strictures and stenosis. Strictures should be treated by stricturoplasty and stenosis by limited resection with Crohn-free resection margins. Just in case of interenteric and enterocutanous with a concomitant short bowel syndrome, in blind-ending fistulas with an abscess or in enterovesical fistulas, we recommend immediate operation. The therapy of recurrent anorectal Crohn's disease underlies the same rules as primary therapy. If necessary, proctectomy remains the last option. Also, emergency surgery in recurrent Crohn's disease follows the same rules as in elective surgery. (+info)
Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn's disease.
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BACKGROUND: Although enteral nutrition is a recognized form of treatment for intestinal Crohn's disease, there are persisting problems with feed palatability and only limited data as to its mode of action. AIM: To assess the effects of a specific oral polymeric diet (CT3211; Nestle, Vevey, Switzerland), which is rich in transforming growth factor beta2, on the mucosal inflammatory process. METHODS: Twenty-nine consecutive children with active intestinal Crohn's disease were treated with CT3211 as the sole source of nutrition for 8 weeks. Patients were assessed clinically, and endoscopically, whilst cytokine mRNA was measured in mucosal biopsies before and after treatment by quantitative reverse transcriptase polymerase chain reaction. RESULTS: After 8 weeks 79% of children were in complete clinical remission. Macroscopic and histological healing in the terminal ileum and colon was associated with a decline in ileal and colonic interleukin-1beta mRNA (pre-treatment to post-treatment ratio 0.008 and 0.06: P < 0.001, P = 0.006). In the ileum there was also a fall in interferon gamma mRNA (ratio 0.15, P < 0.001) with a rise in transforming growth factor beta1 mRNA (ratio 10, P = 0.04), whilst in the colon interleukin-8 mRNA fell with treatment (ratio 0.06, P < 0.05). CONCLUSIONS: The clinical response to oral polymeric diet CT3211 is associated with mucosal healing and a down regulation of mucosal pro-inflammatory cytokine mRNA in both the terminal ileum and colon. In the ileum there was also an increase in transforming growth factor beta1 mRNA. (+info)
High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12.
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Epidemiological studies have shown that genetic factors contribute to the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Recent genome scans and replication studies have identified replicated linkage between CD and a locus on chromosome 16 (the IBD1 locus), replicated linkage between IBD (especially UC) and a locus on chromosome 12q (the IBD2 locus), and replicated linkage between IBD (especially CD) and a locus on chromosome 6p (the IBD3 locus). Since the estimated locus-specific lambdas values for the regions of replicated linkage do not account for the overall lambdas in CD, and since the published genome scans in IBD show at least nominal evidence for linkage to regions on all but two chromosomes, we performed an independent genome scan using 751 microsatellite loci in 127 CD-affected relative pairs from 62 families. Single-point nonparametric linkage analysis using the GENEHUNTER-PLUS program shows evidence for linkage to the adjacent D14S261 and D14S283 loci on chromosome 14q11-12 (LOD = 3.00 and 1.70, respectively), and the maximal multipoint LOD score is observed at D14S261 (LOD = 3.60). In the multipoint analysis, nominal evidence for linkage (P<.05) is observed near D2S117 (LOD = 1.25), near D3S3045 (LOD = 1.31), between D7S40 and D7S648 (LOD = 0.91), and near D18S61 (LOD = 1.15). Our finding of significant linkage to D14S261 and the finding of suggestive linkage to the same locus in an independent study (multipoint LOD = 2.8) satisfies criteria for confirmed linkage, so we propose that the region of interest on chromosome 14q11-12 should be designated the IBD4 locus. (+info)