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Crohn's Disease (crohn's + disease)

Distribution by Scientific Domains

Medical Sciences	98%
2 Other Domains	2%

Distribution within Medical Sciences

Gastroenterology	47%
Gastroenterology & Hepatology	33%
Dermatology	3%
Immunology	2%
20 Other Subdomains	12%

Kinds of Crohn's Disease

active crohn's disease

fistulizing crohn's disease

metastatic crohn's disease

pediatric crohn's disease

perianal crohn's disease

refractory crohn's disease

severe crohn's disease

Terms modified by Crohn's Disease

crohn's disease activity

crohn's disease activity index

crohn's disease patient

Selected Abstracts

Detection of Enterohepatic and Gastric Helicobacter Species in Fecal Specimens of Children with Crohn's Disease

HELICOBACTER, Issue 4 2008
Si Ming Man
Abstract Background: Although there is compelling evidence to support the role of bacteria in Crohn's disease (CD), there is currently no solid evidence to support the role of any one specific bacterial causative agent. Recent studies have suggested that members of the Helicobacteraceae may play a role in the development of CD. The aim of this study was to further investigate the presence of members of the Helicobacteraceae in children with and without CD. Materials and methods: Fecal specimens from 29 children with CD, 11 healthy, normal controls, and 26 symptomatic controls with non-inflammatory bowel disease (IBD) pathology were obtained for DNA extraction and subjected to Helicobacteraceae -specific polymerase chain reaction (PCR). All PCR-positive samples were sequenced. The association between the presence of members of the Helicobacteraceae and each study group was statistically analysed using the Fisher's exact test. Results: Based on Helicobacteraceae -specific PCR analysis, 59% (17 of 29) of the children with CD were positive, which was significantly higher than that in asymptomatic healthy children [9% (1 of 11); p = .01] and that in symptomatic children with non-IBD pathology [0% (0/26); p < .0001]. Sequencing of the 16S rRNA gene of positive samples revealed the presence of both enterohepatic Helicobacter species and Helicobacter pylori in fecal specimens. Conclusions: For the first time, enterohepatic and gastric Helicobacter species have been identified in fecal specimens from children diagnosed with CD using PCR. Our data suggest that Helicobacter species may have a pathogenic role in the development of CD in a considerable proportion of children. [source]

Value of fractional exhaled nitric oxide (FENO) for the diagnosis of pulmonary involvement due to inflammatory bowel disease

INFLAMMATORY BOWEL DISEASES, Issue 4 2010
Ezgi Ozyilmaz MD
Abstract Background: Pulmonary involvement due to inflammatory bowel disease (IBD) is frequent when evaluating a patient with IBD and pulmonary involvement remains complicated. Most of the patients are asymptomatic and the methods used are mostly invasive or expensive procedures. The aim of this prospective study is to evaluate the value of the fractional exhaled nitric oxide (FENO) level for the diagnosis of pulmonary involvement due to IBD and to investigate any correlation between FENO level and disease activity. Methods: Thirty-three nonsmoker patients with IBD (25 ulcerative colitis [UC] and 8 Crohn's Disease [CD]) who were free of corticosteroid treatment and 25 healthy subjects as a control group were enrolled in this study. All patients with IBD were investigated for pulmonary involvement with medical history, physical examination, chest roentgenogram, oxygen saturation, blood eosinophil levels, pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and FENO level. Results: Pulmonary involvement was established in 15 patients (45.5%) with IBD. The FENO level was higher in patients with pulmonary involvement than without pulmonary involvement and healthy controls independent from the pulmonary symptoms, eosinophil count, duration of disease, activity of disease, and surgery history (FENO: 32 ± 20; 24 ± 8; 14 ± 8 ppb, respectively) (P < 0.05). In addition, diffusion capacity (DLCO) was found to be significantly lower in patients with CD compared with UC (P < 0.05). Conclusions: This study showed that an increased FENO level may be used for identifying patients with IBD who need further pulmonary evaluation. Inflamm Bowel Dis 2009 [source]

Patients' attitudes to medicines and adherence to maintenance treatment in inflammatory bowel disease

INFLAMMATORY BOWEL DISEASES, Issue 6 2009
Rob Horne PhD
Abstract Background: Nonadherence has been reported in over 40% of patients taking maintenance therapies (MT) for inflammatory bowel disease (IBD). Studies in other illness groups have shown that nonadherence is related to negative attitudes to treatment. The aim of this study was to assess patients' attitudes to MT for IBD (beliefs about personal need for MT and potential adverse effects) and to identify whether such beliefs are associated with adherence to MT. Methods: A cross-sectional survey was conducted in which 1871 members of the National Association for Colitis and Crohn's Disease (NACC) completed validated questionnaires assessing beliefs about MT and adherence to MT. Results: Low adherence to MT was reported by 29% of participants and was associated with doubts about personal need for MT (odds ratio [OR] = 0.56; 95% confidence interval [CI]: 0.48,0.64; P < 0.001) and concerns about potential adverse effects (OR = 1.66; 95% CI: 1.42,1.94; P < 0.001). Attitudinal analysis showed that while almost half (48%) of the participants were "accepting" of MT (high necessity, low concerns), a large proportion of the sample (42%) were "ambivalent" about MT (high necessity, high concerns), 6% were "sceptical" (low necessity, high concerns) and 4% were "indifferent" (low necessity, low concerns). Compared to those who were "accepting" of MT, participants in all 3 other attitudinal groups were significantly more likely to be nonadherent. Conclusions: The way in which patients judge their personal need for MT relative to their concerns about MT can be a significant barrier to adherence. Interventions to facilitate optimal adherence to MT for IBD should address such perceptual barriers. (Inflamm Bowel Dis 2008) [source]

Further experience with the use of 6-thioguanine in patients with Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 10 2008
Azhar Ansari MD
Abstract Background: 6-Thioguanine (6-TG) is efficacious in patients with Crohn's Disease (CD) failing conventional immunosuppression but there are reports of hepatotoxicity. We report our experience of the safety and efficacy of 6-TG in a series of patients with CD. Methods: A retrospective study of patients with CD who failed thiopurines ± methotrexate between 2001 and 2006 was performed. Indications for 6-TG were; active disease, to allow infliximab withdrawal, steroid sparing, or fistula closure. Patients underwent regular review and those treated longer than 1 year were advised to have liver magnetic resonance imaging (MRI) and liver biopsy. Results: All 30 patients treated with 6-TG during the period were included. The median dose and duration of 6-TG was 40 mg daily and 21.5 months, respectively. Initial clinical response was achieved in 18/30 (60%). Eleven of 29 (38%) (1 unrelated death) remained in remission at a median 44 months follow-up. Seven of 30 (23%) discontinued 6-TG due to adverse effects; 7/30 (23%) patients developed abnormal liver function tests (LFTs) during treatment, mostly transient and mild. One patient developed a portal hypertensive syndrome resolving on cessation of 6-TG. Of 11 liver biopsies, none showed nodular regenerative hyperplasia (NRH). The median red blood cell 6-thioguanine nucleotide (6-TGN) level was 807 pmol/108. Conclusions: 6-TG has good clinical efficacy for third-line immunosuppression in CD but hepatotoxicity remains a concern. However, previous reports of NRH in 6-TG-treated inflammatory bowel disease patients have not been substantiated by this cohort. (Inflamm Bowel Dis 2008) [source]

Crohn's Disease runs a more aggressive course in young asian patients

INFLAMMATORY BOWEL DISEASES, Issue 1 2006
Kelvin Teck Joo Thia MRCP
Abstract Background: Crohn's disease is a heterogeneous inflammatory bowel disease. The impact of age at diagnosis on the clinical course of patients varies widely as reported in the Western literature. Using the Vienna Classification, we seek to determine whether young Crohn's disease patients in an Asian population followed a different clinical course than old patients. Methods: The case records of 100 Crohn's disease patients who were treated at the Inflammatory Bowel Disease Center, Singapore General Hospital, were studied retrospectively. The age group and location of disease and behavior according to the Vienna classification were determined at diagnosis. Results: A1 group (age <40 years) defined as "young" and A2 group (age ,40) defined as "old" contained 65 and 35 patients, respectively. Median age for the young group was 27.4 years and that for the old group was 52.6 years. Of the young patients, 66.7% flared at least once compared with 28.6% of the old patients, odds ratio of 5.0 (P < 0.001). Young patients were more likely to be steroid dependent (20.0% of A1 versus 8.6% of A2, P = 0.14), received azathioprine (38.5% of A1 versus 5.7% of A2, P < 0.001) and experienced complications (31% of A1 versus 20% of A2, P = 0.25)-numerically higher rates that did not reach statistical significance. There was no significant difference between the age groups for the location and behavior of disease as well as requirement for surgery. Conclusion: In this first Asian study looking specifically at the impact of age at diagnosis of Crohn's disease, we found that young patients underwent a more aggressive clinical course. [source]

Influence of standard treatment on ileal and colonic antimicrobial defensin expression in active Crohn's disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009
I. KÜBLER
Summary Background, Crohn's Disease (CD), a chronic intestinal inflammation, is currently treated primarily by therapeutics which are directed against inflammatory responses. Recent findings though suggest a central role of the innate immune barrier in the pathophysiology. Important factors providing this barrier are antimicrobial peptides like the ,- and ,-defensins. Little is known about in vivo effects of common drugs on their expression. Aim, To analyse the influence of corticosteroids, azathioprine and aminosalicylate treatment on ileal and colonic antimicrobial peptides in active CD and also assess the role of inflammation. Methods, We measured the expression of antimicrobial peptides and pro-inflammatory cytokines in 75 patients with active CD. Results, Ileal and colonic ,- and ,-defensins as well as LL37 remained unaffected by corticosteroids, azathioprine or aminosalicylate treatment. Additionally, we did not observe a negative coherency between Paneth cell ,-defensins and any measured cytokines. HBD2 and LL37 unlike HBD1 levels were linked to inflammatory cytokines and increased in highly inflamed samples. Conclusions, Current oral drug treatment seems to have no major effect on the expression of antimicrobial peptides. In contrast to HBD2 and LL37, ileal levels of HD5 and HD6 and colonic HBD1 level are independent of current inflammation. Innovative drugs should aim to strengthen protective innate immunity. [source]

Maintenance of Crohn's disease over 12 months: fixed versus flexible dosing regimen using budesonide controlled ileal release capsules

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2001
J. R. B. Green
Background: It may be possible to achieve more effective management of Crohn's Disease by introducing a flexible dosage regimen sensitive to patients' needs. Aim: Comparison of the efficacy and tolerability of a fixed vs. flexible budesonide controlled ileal release treatment regimen for the prevention and management of relapse in Crohn's disease patients. Budesonide controlled ileal release is an oral formulation which delivers drug directly to disease sites in the ileum and ascending colon, by preventing more proximal release and absorption. Methods: A randomized, double-blind comparison of a fixed dose of budesonide controlled ileal release (6 mg o.m.) and a flexible dose of budesonide controlled ileal release (3, 6 or 9 mg o.m.) for 12 months, in 143 patients in remission from ileal or ileo,caecal Crohn's Disease. Results: Very low rates of clinical relapse in Crohn's disease were achieved with budesonide controlled ileal release 6 mg o.m. There was no significant difference between the treatment groups with respect to the survival estimate of percentage of treatment failures (flexible group 15%, fixed group 19%; P=0.61). The average consumed dose of budesonide was comparable in both groups (5.8 mg flexible, 6.0 mg fixed). Similar proportions of patients reported adverse events (flexible 100%, fixed 97%). There were 33 serious adverse events (flexible 19, fixed 14) and 13 withdrawals due to significant adverse events (flexible 9, fixed 4). Conclusion: Maintenance treatment with budesonide controlled ileal release 6 mg o.m. is well-tolerated and is associated with low rates of clinical relapse in stable Crohn's disease over 12 months. Flexible dosing remains an option for individual patients, but this study has shown no advantage over a standard fixed dosing regimen. [source]

Population-Specific Susceptibility to Crohn's Disease and Ulcerative Colitis; Dominant and Recessive Relative Risks in the Japanese Population

ANNALS OF HUMAN GENETICS, Issue 2 2010
Shigeki Nakagome
Summary Crohn's disease (CD), a type of chronic inflammatory bowel disease (IBD), is commonly found in European and East Asian countries. The calculated heritability of CD appears to be higher than that of ulcerative colitis (UC), another type of IBD. Recent genome-wide association studies (GWAS) have identified more than thirty CD-associated genes/regions in the European population. In the East Asian population, however, a clear association between CD and an associated gene has only been detected with TNFSF15. In order to determine if CD susceptibility differs geographically, nine SNPs from seven of the European CD-associated genomic regions were selected for analysis. The genotype frequencies for these SNPs were compared among the 380 collected Japanese samples, which consisted of 212 IBD cases and 168 controls. We detected a significant association of both CD and UC with only the TNFSF15 gene. Analysis by the modified genotype relative risk test (mGRR) indicated that the risk allele of TNFSF15 is dominant for CD, but is recessive for UC. These results suggest that CD and UC susceptibility differs between the Japanese and European populations. Furthermore, it is also likely that CD and UC share a causative factor which exhibits a different dominant/recessive relative risk in the Japanese population. [source]

P43 Acute urticaria to infliximab

CONTACT DERMATITIS, Issue 3 2004
Ana Giménez-Arnau
Infliximab is a chimeric antitumor necrosis factor-alpha monoclonal antibody used to treat Crohn's disease and rheumatoid arthritis. Acute infusion reactions, headache, fever, chills, urticaria and chest pain were seen in 17% of patients with infliximab compared with 7% of those receiving placebo. Other adverse cutaneous reactions are fungal dermatitis, eczema, seborrhoea, hordeolum, bullous eruption, furunculosis, periorbital oedema, hyperkeratosis, rosacea, verruca, skin pigmentation, alopecia, leukocytoclastic vasculitis, lichenoid drug eruption, erythema multiforme, perniosis-like eruption, granuloma annulare and acute folliculitis. Any pathogenic mechanism has been suggested. Patch test with infliximab can induce flare-up of lesions, nausea and malaise and suggest a percutaneous absortion. A sixty years-old man with atopy background and rheumatoid arthritis treated with Remicare®, infliximab who developed a severe acute urticaria with angioedema is presented. The lesions appearance after previous endovenous administrations and the worsening spreading wheals days after the injection clinically suggested an hypersensitivity mechanism. The protocolized study drug hypersensitivity performed showed only the Prick Test positivity with infliximab at 30/60 minutes. Patch test with infliximab was negative and any adverse event was reported. Actually the patient is treated with etanercept and this drug is well tolerated. This result suggested a type I hypersensitivity mediated reaction. Urticaria could be induced as immunologic reaction of the host against the murine part of infliximab, just as it hapens with other antichimeric antibodies. [source]

Genetic variations associated with psoriasis and psoriatic arthritis found by genome-wide association

DERMATOLOGIC THERAPY, Issue 2 2010
Kristina Callis Duffin
ABSTRACT Psoriasis and psoriatic arthritis are immune disorders with a complex polygenic basis. HLA-Cw6, which lies in the major histocompatibility region on chromosome 6, is considered the major genetic determinant of psoriasis. Recent genome-wide association studies have identified new variants outside of the MHC with relevance to the immunology of psoriasis. Variants in or near genes that encode subunits of cytokines (IL12B, IL23A) or cytokine receptors (IL23R) are interesting given that the gene product of IL12B, p40, is the target of a recently approved monoclonal antibody therapy for psoriasis (ustekinumab). Association with psoriasis and psoriatic arthritis has been found in TNFAIP3 and TNFIP1, ubiquitin ligases in the NF-,B pathway, and IL13, a Th2 cytokine. Copy number variation of human beta-defensin and late cornified envelope genes also associate with psoriasis. Many of these genetic variations also associate with immune disorders considered psoriatic co-morbidities, including Crohn's disease and diabetes. [source]

Evaluation of gastroduodenal mucosal lesions in patients with Crohn's disease and ulcerative colitis

DIGESTIVE ENDOSCOPY, Issue 3 2004
Kazuhiro Maeda
Background:, Patients with Crohn's disease (CD) are reported to suffer from upper gastroduodenal lesions with varying frequency, although concurrent Helicobacter pylori infection is reported to be low. Methods:, A prospective study was carried out on patients diagnosed with CD or ulcerative colitis (UC) in order to evaluate the degree of upper gastroduodenal tract involvement and the prevalence of Helicobacter pylori infection. Results:, Gastroduodenal lesions were found in 18 (78%) of 23 CD patients, the location being the stomach in 18 (78%), the duodenal bulb in 16 (70%) and the descending duodenum in 16 (70%). Bamboo joint-like lesions were found in four cases (17%) in gastric body and cardia. In contrast, gastroduodenal lesions were found in 10 (53%) of 19 UC patients, the location being the stomach in nine (47%), the duodenal bulb in six (32%), and the descending duodenum in three (16%). The H. pylori -positive rate in patients with CD and UC was 0%, and 11%, respectively. Conclusion:, Minute upper gastroduodenal lesions are much more common in CD than in UC patients, especially in the descending duodenum. Accordingly, upper gastrointestinal endoscopy would seem to be a useful means with which to obtain a definitive diagnosis in all suspected IBD cases. [source]

Surveillance colonoscopy for colitic cancer in inflammatory bowel disease

DIGESTIVE ENDOSCOPY, Issue 4 2003
Keisuke Hata
Patients with inflammatory bowel disease are known to be at increased risk for the development of colorectal cancer, especially those with long-standing extensive ulcerative colitis. Although some recommend prophylactic total proctocolectomy for these high-risk patients, surveillance colonoscopy to detect ulcerative colitis-associated colorectal cancer is, instead, generally performed. Dysplasia has been considered to be a useful marker to detect colorectal cancer at surveillance colonoscopy. High-grade dysplasia is a definite indication for total proctocolectomy, while management of low-grade dysplasia is still controversial. Patients with Crohn's disease are also considered to be at higher risk for the development of colorectal cancer, although the risk may be lower than in extensive ulcerative colitis. Molecular biology-based surveillance and chemoprevention for ulcerative colitis-associated colorectal cancer are also reviewed. [source]

The clinical pharmacology of therapeutic monoclonal antibodies

DRUG DEVELOPMENT RESEARCH, Issue 3 2004
Lorin K. Roskos
Abstract Seventeen monoclonal antibodies are currently approved in the United States for therapeutic use in organ transplantation, percutaneous coronary intervention, prophylaxis of respiratory syncytial virus disease, rheumatoid arthritis, Crohn's disease, asthma, chronic lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, breast cancer, and colorectal cancer. All approved antibodies are of the IgG class. Thirteen are unconjugated intact antibodies, three are intact immunoconjugates, and one is a Fab fragment. Three of the antibodies are murine, five are chimeric, eight are humanized, and one is a fully human antibody generated by phage display technology. The antigen target and the structural and binding characteristics of the antibody determine the antibody's mechanism of action, pharmacokinetics, safety, and immunogenicity. Antibodies act through multiple mechanisms that include functional modulation of the antigen, recruitment of ADCC and CDC, and delivery of radionuclide or toxin payloads to target cells. Antibody half-life is usually governed by interaction with the FcRn receptor. In some cases, the antigen may act as a sink for antibody elimination. Safety profiles are determined by the pharmacology and tissue distribution of the target antigen, antibody isotype, the antibody payload, cytokine release, hypersensitivity reactions to xenogeneic protein, and immunogenicity. Fully human antibody technology may allow development of antibodies that have reduced risks of hypersensitivity reactions and immunogenicity, thereby enhancing safety and efficacy. The exquisite target specificity of antibodies, improvements in antibody engineering technology, and the wide availability of novel and validated therapeutic targets provide many current and future opportunities for the clinical development of therapeutic antibodies. Drug Dev. Res. 61:108,120, 2004. © 2004 Wiley-Liss, Inc. [source]

Potential role of soluble angiopoietin-2 and Tie-2 in patients with inflammatory bowel disease

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2006
I. E. Koutroubakis
Abstract Background, Angiogenesis has been suggested to play an important role in inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD). Materials and methods, Serum Ang-2 and Tie-2 serum levels were measured in 160 IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2 levels were correlated with the disease activity, as well as the type, localization and treatment of the disease. Results, Median serum Ang-2 and Tie-2 levels were significantly higher in both the UC patients and the CD patients compared with the healthy controls (P < 0·05 and P < 0·001, respectively). The IBD patients with early disease (diagnosis < 2 years) had significantly higher (P = 0·04) median serum Ang-2 levels but significantly lower (P = 0·02) median serum Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2 years). The CD patients with active disease had significantly higher levels of Ang-2 compared with non-active disease (P = 0·02). Serum levels of both Ang-2 and Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood cell count, platelet count and albumin. Conclusions, Serum Ang-2 and Tie-2 levels are elevated in patients with IBD. These markers may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD. [source]

Platelet factor 4 and ,-thromboglobulin in inflammatory bowel disease and giant cell arteritis

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2000
Vrij
Background As platelet factors are important in the inflammatory response, we examined the course of platelet factor 4 and ,-thromboglobulin in relation to disease activity in inflammatory bowel disease and in giant cell arteritis. Patients and methods In a prospective study, the platelet count, platelet factor 4 and ,-thromboglobulin were measured in 20 patients with Crohn's disease, 18 with ulcerative colitis and 19 with giant cell arteritis, during active and inactive disease, as well as in 51 controls without inflammation. Results Platelet counts were significantly higher in active vs. inactive Crohn's disease, ulcerative colitis and giant cell arteritis. Levels of platelet factor 4 and ,-thromboglobulin were significantly higher in active inflammatory bowel disease and giant cell arteritis, as well as in inactive inflammatory bowel disease and giant cell arteritis, than in the non-inflammatory controls. A positive correlation was found between the Crohn's disease activity index and the platelet count, platelet factor 4 and ,-thromboglobulin. Also, a positive correlation was found between the ulcerative colitis activity index and ,-thromboglobulin. However, even after 12 months of follow-up, in Crohn's disease and ulcerative colitis the mean levels of platelet factor 4 and ,-thromboglobulin were significantly higher than the levels of the controls. Conclusion Platelet factors were correlated with inflammatory bowel disease activity. Levels of platelet factor 4 and ,-thromboglobulin, however, were markedly raised for a long time in clinically inactive inflammatory bowel disease, which might point to a pre-thrombotic state of disease. [source]

Genetics of inflammasome-associated disorders: A lesson in the guiding principals of inflammasome function

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2010
Ian Gaël Rodrigue-Gervais
Abstract Human genetics research has had a great impact on the genesis of the inflammasome field and the treatment of certain inflammasomopathies. The identification of mutations causing rare autoinflammatory syndromes, reproductive wastage disorders and of single nucleotide polymorphisms influencing susceptibility to complex diseases such as vitiligo, sepsis, and Crohn's disease has not only led to the characterization of novel proteins involved in NOD-like receptor-coupled inflammatory signaling pathways but also to greater insights into pathogenic mechanisms. [source]

NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's disease

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2004
Mihai
Abstract Mutations of the NOD2 gene have been associated with an increased susceptibility to Crohn's disease, but the pathogenetic mechanisms mediated by NOD2 remain elusive. In the present study, we demonstrate that the 3020insC frameshift-mutation in the NOD2 gene associated with Crohn's disease results in defective release of IL-10 from blood mononuclear cells after stimulation with the Toll-like receptor (TLR)2 ligands, peptidoglycan and Pam3Cys-KKKK, but not with bacterial LPS, a TLR4 ligand. The potential pathophysiological significance of this finding in patients with Crohn's disease and who are homozygous for this NOD2 mutation was substantiated by the finding of decreased anti-inflammatory cytokine release when cells from these patients were stimulated with different species of Bacteroides, an enteric microorganism implicated in the pathogenesis of Crohn's disease. In conclusion, defective NOD2 function results in a pro-inflammatory cytokine bias after stimulation of mononuclear cells with TLR2 stimuli, and this could contribute to the overwhelming inflammation seen in Crohn's disease. See Mini-review in this issue http://dx.doi.org/10.1002/eji.200425095 [source]

The 3020insC mutation of the NOD2/CARD15 gene in patients with periodontal disease

EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2004
Matthias Folwaczny
The 3020insC mutation of the NOD2/CARD15 gene leads to impaired activation of nuclear factor-kappa B (NF- ,B) in vitro. As the destruction of periodontal tissue is mediated via activation of NF- ,B, with subsequent transcription of proinflammatory cytokines, the c-insertion mutation of the NOD2/CARD15 gene might contribute to the proposed genetic background of periodontitis. The present study analysed the frequency of this mutation in 80 patients with chronic periodontal disease and 122 healthy controls. The 3020insC mutation was identified by employing the polymerase chain reaction followed by restriction fragment length polymorphism analysis. The prevalence of the 3020insC mutation of the NOD2/CARD15 protein in patients with periodontitis was 1.9% (three of 160) and that for the control group was 2.0% (five of 244) (P = 0.942). Hence, unlike in Crohn's disease, the 3020insC mutation of the NOD2/CARD15 gene does not seem to influence the pathophysiology of periodontitis. [source]

Granulomatous rosacea and Crohn's disease in a patient homozygous for the Crohn-associated NOD2/CARD15 polymorphism R702W

EXPERIMENTAL DERMATOLOGY, Issue 12 2008
M. A. M. Van Steensel
Abstract:, NOD2/CARD15 belongs to the N-terminal caspase recruitment domain family of proteins involved in regulating NF-kB activation in response to inflammatory stimuli transduced through Toll-like receptors. Mutations and polymorphisms in the NOD2/CARD15 gene reduce antibacterial responses and are associated with granulomatous inflammatory conditions such as Blau syndrome and early-onset sarcoidosis. The polymorphism R702W (arginine to tryptophan) is strongly associated with susceptibility to Crohn's disease in Caucasian populations. Skin abnormalities (other than cutaneous manifestations of Crohn's disease) have not been previously associated with R702W. We report on a female patient homozygous for R702W who developed granulomatous rosacea at the age of 12 years old. From the occurrence in the context of Crohn associated with R702W, we speculate that granulomatous rosacea may be an entity distinct from other forms of rosacea, which are associated with increased production of antibacterial proteins such as cathelicidin. [source]

The role of stem cells in suppurative environments

EXPERIMENTAL DERMATOLOGY, Issue 6 2006
Dolores Herreros
Purpose:,The management of suppurative perianal lesions presents an extremely challenging problem. Stem cells (SC) extracted from certain tissues, such as adipose tissue, can differentiate into various cell types. Therefore, we have tried to use such cells to stimulate healing in a purulent environment. Methods:,In the beginning, we designed a phase I clinical trial, involving five patients with Crohn's disease. We inoculated nine fistulas in four patients with autologous adipose-derived stem cells (ADSC) and were followed at least 8 weeks. Seventy-five percent became healed, and 25% showed a decrease in output flow. No adverse effects were observed in any patient. This study evidenced that such cells are safe. Then, we started a research line using SC in different suppurative environments. During the course of these studies, we had the opportunity to treat a patient with perianal hidradenitis suppurativa using our current protocol of ADSC transplantation. Eight weeks after injection, patient had no perianal suppuration, and a year later remains well. Discussion:,The biological mechanism that underlies the therapeutic success of ADSC transplantation is unknown. Cell differentiation, secretion of growth factors or immunomodulatory effects have been suggested. No ethical conflicts were identified by our Ethics Committee, because the cells were autologous. Conclusions:,Our study shows that ADSC are safe for the treatment of suppurative processes. The actual number of patients included and the uncontrolled nature of these pilot studies do not allow demonstration of the effectiveness of the treatment. However, the results encourage the performance of further studies. [source]

A Crohn's disease-associated insertion polymorphism (3020insC) in the NOD2 gene is not associated with psoriasis vulgaris, palmo-plantar pustular psoriasis or guttate psoriasis

EXPERIMENTAL DERMATOLOGY, Issue 4 2003
C. Young
Abstract: A C-insertion polymorphism in the NOD2 gene (3020insC) on chromosome 16 is a rare mutation associated with Crohn's disease. Crohn's disease and psoriasis are more commonly observed together than expected by chance. Furthermore a susceptibility locus for psoriasis has been identified on chromosome 16q which overlaps the recently identified susceptibility locus for Crohn's disease. Thus, NOD2 may potentially be important as a candidate susceptibility gene for psoriasis. We tested this hypothesis by genotyping psoriasis patients for the C-insertion polymorphism using the Taqman ABI 7700 sequencing system. No statistically significant differences were observed between psoriasis vulgaris (n = 216), palmo-plantar pustular psoriasis (PPP) (n = 100), guttate psoriasis (n = 118) and the control group (n = 283). In both patient and control groups, no mutant homozygotes were observed and approximately 4% were heterozygotes. This particular insertion mutation in the NOD2 gene does not appear to contribute to the genetic susceptibility of psoriasis vulgaris, PPP or guttate psoriasis. However, other mutations exist in the NOD2 gene, which may potentially have a role in psoriasis susceptibility. [source]

Catalytic digestion of human tumor necrosis factor-, by antibody heavy chain

FEBS JOURNAL, Issue 18 2010
Emi Hifumi
It has long been an important task to prepare a catalytic antibody capable of digesting a targeting crucial protein that controls specific life functions. Tumor necrosis factor-, (TNF-,) is a cytokine and an important molecule concerned with autoimmune diseases such as rheumatoid arthritis, chronic obstructive pulmonary disease, and Crohn's disease. A mAb (ETNF-6 mAb) raised against human TNF-, was prepared, and the steric conformation was created by using molecular modeling after the cDNA was sequenced. The heavy chain (ETNF-6-H) of the mAb was considered to possess a catalytic triad-like structure in the complementarity determining regions (CDRs). As a result, ETNF-6-H exhibited a peptidase and a protease activity. In fact, ETNF-6-H predominantly cleaved the Ser5-Arg6 bond of TNF-, at the first step, resulting in the generation of a fragment of , 17 kDa. This fragment was digested to a smaller molecule of 15 kDa by scission of the Gln21-Ala22 bond. The intermediate product was further converted into a fragment of 13.3 kDa by successive cleavage of the Leu36-Leu37 and Asn39-Gly40 bonds. The heavy chain possessed a protease activity against TNF-, with a multicleavage site. [source]

Detection of Enterohepatic and Gastric Helicobacter Species in Fecal Specimens of Children with Crohn's Disease

Squamous metaplasia of the colon in Crohn's disease

HISTOPATHOLOGY, Issue 4 2007
C Langner
No abstract is available for this article. [source]

Diagnostic difficulties in inflammatory bowel disease pathology

HISTOPATHOLOGY, Issue 2 2006
R K Yantiss
This review summarizes some of the common diagnostic problems encountered by pathologists when evaluating patients with chronic colitis and in whom inflammatory bowel disease (IBD) is either suspected or within the differential diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of ,indeterminate colitis' (IC). However, other reasons why pathologists may entertain a diagnosis of IC include failure to recognize or accept certain ,hardcore' histological features as indicative of CD, an attempt to classify cases of chronic colitis based on mucosal biopsy material or in the absence of adequate clinical and radiographic information, and the presence of other disease processes that mask, or mimic, IBD. In addition, some cases of UC may show unusual CD-like features, such as discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis and diversion colitis may, on occasion, also show IBD-like changes. The clinical and pathological features that aid in the distinction between these entities, and others, are covered in detail in this review. [source]

Genetics and genomics of ankylosing spondylitis

IMMUNOLOGICAL REVIEWS, Issue 1 2010
Gethin P. Thomas
Summary:, Ankylosing spondylitis (AS) is a common, highly heritable arthropathy, the pathogenesis of which is poorly understood. The mechanism by which the main gene for the disease, HLA-B27, leads to AS is unknown. Genetic and genomic studies have demonstrated involvement of the interleukin-23 (IL-23) signaling pathway in AS, a finding which has stimulated much new research into the disease and has led to therapeutic trials. Several other genes and genetic regions, including further major histocompatibility complex (MHC) and non-MHC loci, have been shown to be involved in the disease, but it is not clear yet how they actually induce the condition. These findings have shown that there is a strong genetic overlap between AS and Crohn's disease in particular, although there are also major differences in the genes involved in the two conditions, presumably explaining their different presentations. Genomic and proteomic studies are in an early phase but have potential both as diagnostic/prognostic tools and as a further hypothesis-free tool to investigate AS pathogenesis. Given the slow progress in studying the mechanism of association of HLA-B27 with AS, these may prove to be more fruitful approaches to investigating the pathogenesis of the disease. [source]

The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease

IMMUNOLOGY, Issue 2 2008
Megan E. Himmel
Summary Two related chronic inflammatory diseases, Crohn's disease and ulcerative colitis, are together often referred to as inflammatory bowel disease (IBD). Current treatment options are not curative, and patients face lifelong therapy and debilitation. IBD is thought to be the product of a combination of genetic and environmental factors that result in the abnormal regulation of immune responses. Experimental models have demonstrated that normal CD4+ T-regulatory (Treg) cell responses and commensal bacteria are required for the maintenance of gut immune homeostasis. Recent evidence that CD4+ T cells express Toll-like receptors (TLRs) and respond directly to TLR ligands, suggests that signals from commensal bacteria may directly affect T-cell responses in the gut. In this review, we focus on evidence that defects in Treg cells may underlie IBD in humans. In addition, we discuss evidence that direct signaling via TLRs to T cells can affect IBD and that T-cell-dependent responses to bacterial proteins, such as flagellin, are central to the aetiology of this disease. [source]

Anti tumour necrosis-, therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's disease

IMMUNOLOGY, Issue 2 2008
Ida Ricciardelli
Summary Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-, shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn's disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription,polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF-,, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF-, immunotherapy can also restore mucosal homeostasis in Crohn's disease. [source]

Sulphasalazine inhibits macrophage activation: inhibitory effects on inducible nitric oxide synthase expression, interleukin-12 production and major histocompatibility complex II expression

IMMUNOLOGY, Issue 4 2001
György Haskó
Summary The anti-inflammatory agent sulphasalazine is an important component of several treatment regimens in the therapy of ulcerative colitis, Crohn's disease and rheumatoid arthritis. Sulphasalazine has many immunomodulatory actions, including modulation of the function of a variety of cell types, such as lymphocytes, natural killer cells, epithelial cells and mast cells. However, the effect of this agent on macrophage (M,) function has not been characterized in detail. In the present study, we investigated the effect of sulphasalazine and two related compounds , sulphapyridine and 5-aminosalicylic acid , on M, activation induced by bacterial lipopolysaccharide (LPS) and interferon-, (IFN-,). In J774 M, stimulated with LPS (10 µg/ml) and IFN-, (100 U/ml), sulphasalazine (50,500 µm) suppressed nitric oxide (NO) production in a concentration-dependent manner. The expression of the inducible NO synthase (iNOS) was suppressed by sulphasalazine at 500 µm. Sulphasalazine inhibited the LPS/IFN-,-induced production of both interleukin-12 (IL-12) p40 and p70. The suppression of both NO and IL-12 production by sulphasalazine was superior to that by either sulphapyridine or 5-aminosalicylic acid. Although the combination of LPS and IFN-, induced a rapid expression of the active forms of p38 and p42/44 mitogen-activated protein kinases and c-Jun terminal kinase, sulphasalazine failed to interfere with the activation of any of these kinases. Finally, sulphasalazine suppressed the IFN-,-induced expression of major histocompatibility complex class II. These results demonstrate that the M, is an important target of the immunosuppressive effect of sulphasalazine. [source]

Healing of anastomotic enterocutaneous fistulae due to Crohn's disease by anti-tNF-alpha antibodies

INFLAMMATORY BOWEL DISEASES, Issue 10 2010
Pierre-Alain Cougard MD
No abstract is available for this article. [source]