Primary antibody deficiency and Crohn's disease.
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Five patients with primary antibody deficiency were investigated because of intermittent but persistent diarrhoea of several years duration despite immunoglobulin replacement therapy. We found no evidence of Giardia lambia or other intestinal pathogens to explain their gastrointestinal symptoms. All five had definite radiological evidence of small bowel Crohn's disease and three had histological specimens available with abnormalities consistent with Crohn's disease. One patient had a non-caseating granuloma in an oral ulcer. A second patient with stricturing disease in the small bowel had a mucosal inflammatory infiltrate with non-caseating granulomas. A third had transmural inflammation but no granulomas. All five patents were diagnosed as having Crohn's disease and have responded symptomatically to steroid therapy. (+info)
Invasive ability of an Escherichia coli strain isolated from the ileal mucosa of a patient with Crohn's disease.
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Crohn's disease (CD) is an inflammatory bowel disease in which Escherichia coli strains have been suspected of being involved. We demonstrated previously that ileal lesions of CD are colonized by E. coli strains able to adhere to intestinal Caco-2 cells but devoid of the virulence genes so far described in the pathogenic E. coli strains involved in gastrointestinal infections. In the present study we compared the invasive ability of one of these strains isolated from an ileal biopsy of a patient with CD, strain LF82, with that of reference enteroinvasive (EIEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteraggregative (EAggEC), enterohemorrhagic (EHEC), and diffusely adhering (DAEC) E. coli strains. Gentamicin protection assays showed that E. coli LF82 was able to efficiently invade HEp-2 cells. Its invasive level was not significantly different from that of EIEC and EPEC strains (P > 0.5) but significantly higher than that of ETEC (P < 0.03), EHEC (P < 0. 005), EAggEC (P < 0.004) and DAEC (P < 0.02) strains. Strain LF82 also demonstrated efficient ability to invade intestinal epithelial cultured Caco-2, Intestine-407, and HCT-8 cells. Electron microscopy examination of infected HEp-2 cells revealed the presence of numerous intracellular bacteria located in vacuoles or free in the host cell cytoplasm. In addition, the interaction of strain LF82 with epithelial cells was associated with the elongation of microvillar extensions that extruded from the host cell membranes and engulfed the bacteria. This internalization mechanism strongly resembles Salmonella- or Shigella-induced macropinocytosis. The use of cytochalasin D and colchicine showed that the uptake of strain LF82 by HEp-2 cells was mediated by both an actin microfilament-dependent mechanism and microtubule involvement. In addition, strain LF82 survived for at least 24 h in HEp-2 and Intestine-407 cells and efficiently replicated intracellularly in HEp-2 cells. PCR and hybridization experiments did not reveal the presence of any of the genetic determinants encoding EIEC, EPEC, or ETEC proteins involved in bacterial invasion. Thus, these findings show that LF82, which colonized the ileal mucosa of a patient with CD, is a true invasive E. coli strain and suggest the existence of a new potentially pathogenic group of E. coli, which we propose be designated adherent-invasive E. coli. (+info)
Endotoxin contamination in isolation of lamina propria mononuclear cells.
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Because the beginning of extraction of lamina propria mononuclear cells is to obtain mucosal tissues that are exposed to luminal bacteria, the contaminated endotoxin in this step and/or the enzymes for mucosal digestion may activate mucosal macrophages and other cells. To address this issue, endotoxin levels in isolation solutions were evaluated during the extraction of lamina propria mononuclear cells from 8 control, 7 Crohn's disease and 8 ulcerative colitis specimens. Endotoxin levels were measured using Toxicolor system based on the limulus tests. Endotoxin levels were consistently below 500 pg/ml, and more importantly, these in enzyme digestion solutions were comparable among control, Crohn's disease, and ulcerative colitis. Therefore, comparative experiments using lamina propria mononuclear cells from these mucosae can be appropriately carried out, at least as far as in a comparable amount of contaminated endotoxin. However, careful consideration is required for the comparative and functional study using peripheral blood and lamina propria mononuclear cells. (+info)
Selective COX-2 inhibitors and human inflammatory bowel disease.
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BACKGROUND: Much recent effort has been made to produce selective inhibitors of cyclo-oxygenase-2 (COX-2) in the belief that these will lack the gastrointestinal damaging effects of traditional non-steroidal anti-inflammatory drugs (NSAIDs). Inflammatory bowel disease is associated with increased local production of prostanoids. These prostanoids, particularly PGE2 and PGI2, may well be protective as inflammatory bowel disease is aggravated by NSAID use. AIM: To examine the effects of a traditional NSAID and a highly selective COX-2 inhibitor on the production of these prostanoids in human inflammatory bowel disease. METHODS: Colonic mucosal biopsies were obtained from patients undergoing routine colonoscopy and biopsy for diagnostic or surveillance purposes. Biopsies were incubated in culture medium containing 10% foetal calf serum and antibiotics, plus test drugs or vehicle for 24 h, after which time the medium was removed and the content of PGE2, PGI2 (measured as 6 keto-PGF1alpha) and thromboxane (Tx) A2 (measured as TxB2) determined. RESULTS: Biopsies obtained from diseased colonic mucosa produced significantly more PGE2, PGI2 and thromboxane A2 than did controls (for example, PGE2: ulcerative colitis, 4.17+/-1.06; Crohn's disease, 3.97+/-1.66; control, 0.12 +/-0.13 ng/mL, n = 8-12). These increases were inhibited to a similar extent by either a highly selective COX-2 inhibitor (L-745,337) or a traditional non-selective NSAID (indomethacin). CONCLUSIONS: Until selective COX-2 inhibitors have been assessed adequately in human inflammatory bowel disease, these compounds should not be assumed to be safe for the gastrointestinal tract in inflammatory bowel disease. (+info)
Ulcerative colitis and colorectal cancer: a follow-up study in Fukuoka, Japan.
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BACKGROUND: Our goal was to study the higher death rate and the causes of such deaths among ulcerative colitis (UC) patients in the Japanese population, and to compare our findings in such cases with those for Crohn's disease (CD). METHODS: In all, 174 UC (male/female: 54/120) and 66 CD (34/32) patients who were registered for the research promotion programme in Fukuoka prefecture (1971-1981) were traced up to the end of 1994. The standardized mortality ratios (SMR) were calculated based on the death rates of the Japanese population by age, sex and calendar year. RESULTS: The overall follow-up rate was 96.7%. Among the UC patients, the SMR for all causes were 0.84 (95% CI: 0.11-4.31) for men; 1.05 (95% CI: 0.08-4.69) for women; and 0.94 (95% CI :0.09-4.50) for both sexes combined. When excluding deaths due to colorectal cancer, the SMR for the same groups were 0.43, 0.94 and 0.67, respectively. The SMR for both sexes were 1.82 (95% CI: 0.17-5.96) for malignant neoplasms and 9.93 (95% CI: 4.67-17.3) for colorectal cancer. Patients who died from colorectal cancer showed onset at a younger age (mean: 25.5 years) as well as a longer disease course of UC (mean: 17.0 years). Regarding the CD patients, the SMR for all causes were 1.75 (95% CI: 0.15-5.75) for both sexes. Most deaths were caused by gastrointestinal complications. CONCLUSIONS: An excess mortality from colorectal cancers was indicated in the UC patients, especially in males. The overall SMR in male UC patients decreased by 50% when the deaths from colorectal cancer were excluded. The excess mortality in those with CD over UC patients was attributed to gastrointestinal complications rather than malignant diseases. Some carcinogenic factors therefore seem most likely to exist in the pathogenesis of UC. (+info)
Endoscopic mucosal biopsies are useful in distinguishing granulomatous colitis due to Crohn's disease from tuberculosis.
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BACKGROUND: Intestinal tuberculosis and Crohn's disease are chronic granulomatous disorders that are difficult to differentiate histologically. AIMS: To characterise distinctive diagnostic features of tuberculosis and Crohn's disease in mucosal biopsy specimens obtained at colonoscopy. METHODS: Selected histological parameters were evaluated retrospectively in a total of 61 biopsy sites from 20 patients with tuberculosis and 112 biopsy sites from 20 patients with Crohn's disease. The patients were chosen on the basis of clinical history, colonoscopic findings, diagnostic histology, and response to treatment. RESULTS: The histological parameters characteristic of tuberculosis were multiple (mean number of granulomas per section: 5.35), large (mean widest diameter: 193 microm), confluent granulomas often with caseating necrosis. Other features were ulcers lined by conglomerate epithelioid histiocytes and disproportionate submucosal inflammation. The features characteristic of Crohn's disease were infrequent (mean number of granulomas per section: 0.75), small (mean widest diameter: 95 microm) granulomas, microgranulomas (defined as poorly organised collections of epithelioid histiocytes), focally enhanced colitis, and a high prevalence of chronic inflammation, even in endoscopically normal appearing areas. CONCLUSIONS: The type and frequency of granulomas, presence or absence of ulcers lined by epithelioid histiocytes and microgranulomas, and the distribution of chronic inflammation have been identified as histological parameters that can be used to differentiate tuberculosis and Crohn's disease in mucosal biopsy specimens obtained at colonoscopy. (+info)
Crohn's disease mimicking sarcoidosis in bronchoalveolar lavage.
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Granulomatous disorders like sarcoidosis or Crohn's disease are commonly associated with extrapulmonary or extraintestinal manifestations which occasionally may represent the only symptoms. We describe a 28-year-old female patient suffering from atypical erythema nodosum and arthritis. Although the chest x-ray was unremarkable bronchoalveolar lavage revealed lymphocytic alveolitis with an elevated CD4/CD8 ratio of 8 and 11.4 at repeated examinations suggesting a diagnosis of sarcoidosis. Further diagnostic workup included endoscopy of the bowel. The macroscopic aspect and histology of the terminal small bowel and colon ascendens indicated Crohn's disease. The patient recovered on steroids and sulfasalazine. Six months later she developed a perianal abscess for which she needed surgery supporting the diagnosis of Crohn's disease. This is the first case of a significantly (>6) elevated CD4/CD8 ratio in Crohn's disease previously regarded as highly specific for sarcoidosis. (+info)
Cell specific effects of glucocorticoid treatment on the NF-kappaBp65/IkappaBalpha system in patients with Crohn's disease.
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BACKGROUND/AIMS/PATIENTS: Glucocorticoid treatment is known to reduce nuclear factor-kappa B (NF-kappaB)p65 binding activity and activation in lamina propria cells of patients with Crohn's disease. However, lamina propria cells of glucocorticoid treated patients did not show increased expression of IkappaBalpha, and the hypothesised upregulation of IkappaBalpha by glucocorticoid treatment has not yet been shown in vivo. To investigate whether cells other than lamina propria localised mononuclear cells contribute to increased IkappaBalpha, resection gut specimens from patients matched for Crohn's disease activity index (CDAI) with or without glucocorticoid treatment were studied, and changes in the NF-kappaB/IkappaBalpha system were determined in the lamina propria as well as in underlying submucosal and endothelial cells. METHODS: Changes in the NF-kappaB/IkappaBalpha system were determined by immunohistochemistry, electrophoretic mobility shift assay, and western blot analysis in resected gut specimens from patients matched for CDAI and van Hees index with or without long term glucocorticoid treatment. RESULTS: Resection gut specimens from patients with Crohn's disease under glucocorticoid treatment had significantly lower nuclear NF-kappaBp65 levels in mononuclear, epithelial, and endothelial cells than samples from CDAI and van Hees index matched patients not having glucocorticoid treatment. Nuclear NF-kappaBp65 showed a strong positive correlation with both the CDAI (r = 1 for both groups) and the van Hees index (r = 0.605 for untreated and r = 0.866 for glucocorticoid treated specimens). Lower nuclear translocation of NF-kappaBp65 in the glucocorticoid treated group was paralleled by higher IkappaBalpha levels in vascular endothelial cells, but not in infiltrating mononuclear cells. CONCLUSION: A comparison of resection gut specimens from untreated and treated CDAI matched patients with Crohn's disease showed downregulation of NF-kappaB binding activity and NF-kappaBp65 expression and cell specific induction of endothelial IkappaBkappa expression in the glucocorticoid treated group. As the two groups showed similar disease activity (CDAI, van Hees index), the activation of the NF-kappaBp65/IkappaBalpha system must be only part of the inflammatory cascade leading to the clinical appearance of Crohn's disease. (+info)