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PubMed2006

Contribution of IBD5 locus to clinical features of IBD patients.

AIM: The aim of this study was to investigate the influence of the IBD5 locus on clinical features of inflammatory bowel disease (IBD) patients, and its possible interaction with the CARD15 gene. PATIENTS AND METHODS: A cohort of 1,199 IBD patients (570 with CD and 629 with ulcerative colitis [UC]), and 357 healthy subjects were investigated. Information on clinical features was fully available for 855 IBD patients. Two SNPs in the IBD5 locus (IGR2198a_1 and IGR2096a_1) and the three major variants of CARD15 gene were genotyped in patients and controls. RESULTS: Homozygous carriers of risk alleles were significantly more frequent in CD (22.6% for IGR2198a_1, OR = 1.6, p = 0.015; 21.9% for IGR2096a_1, OR = 1.6, p = 0.012) compared to controls (16.8% and 15.7%, respectively). The homozygote frequency was also increased in UC patients, but not significantly. No significant gene-gene interaction was detected between IBD5 and CARD15. A univariate analysis detected association between IBD5 and steno/fistulizing behavior in CD patients (OR = 1.9; p = 0.004), and presence of more extensive colitis in UC patients (OR = 1.7; p = 0.01). Results from multiple logistic regression, after correction for covariates, showed that the influence of IBD5 on clinical outcome of CD was completely masked by that of CARD15, while the influence on more extensive colitis in UC patients was confirmed. CONCLUSIONS: Our study shows that presence of the IBD5 risk alleles, particularly in the homozygous state, is associated with IBD and especially with CD, without a significant epistasis with CARD15. The contribution of CARD15 risk alleles to CD clinical features is prominent on that of IBD5.

Adolescent↗
PubMed1996

Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD).

BACKGROUND: It has been suggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is three or more times higher in northern than in southern Europe. The aim of this EC funded study was to investigate this apparent variation by ascertaining the incidence of IBD across Europe. METHODS: For the period 1 October 1991 to 30 September 1993 all new patients diagnosed with IBD were prospectively identified in 20 European centres according to a standard protocol for case ascertainment and definition. FINDINGS: Altogether 2201 patients aged 15 years or more were identified, of whom 1379 were diagnosed as UC (including proctitis), 706 as CD, and 116 as indeterminate. The overall incidence per 100,000 at ages 15-64 years (standardised for age and sex) of UC was 10.4 (95% confidence interval (95% CI) 7.6 to 13.1) and that of CD was 5.6 (95% CI 2.8 to 8.3). Rates of UC in northern centres were 40% higher than those in the south (rate ratio (RR) = 1.4 (95% CI 1.2 to 1.5)) and for CD they were 80% higher (RR = 1.8 (95% CI 1.5 to 2.1)). For UC the highest reported incidence was in Iceland (24.5, 95% CI 17.4 to 31.5) and for CD, Maastricht (The Netherlands; 9.2, 95% CI 6.5 to 11.8) and Amiens (north west France; 9.2, 95% CI 6.3 to 12.2). The lowest incidence of UC was in Almada (southern Portugal) (1.6, 95% CI 0.0 to 3.2) and of CD in Ioannina (north west Greece) (0.9, 95% CI 0.0 to 2.2). An unexpected finding was a difference in the age specific incidence of UC in men and women with the incidence in women but not men declining with age. INTERPRETATION: The higher overall incidence rates in northern centres did not seem to be explained by differences in tobacco consumption or education. Nevertheless, the magnitude of the observed excess for both conditions is less than expected on the basis of previous studies. This may reflect recent increases in the incidence of IBD in southern Europe whereas those in the north may have stabilised.

Adolescent↗
PubMedDate not supplied

Ursodeoxycholic acid treatment in IBD-patients with colorectal dysplasia and/or DNA-aneuploidy: a prospective, double-blind, randomized controlled pilot study.

BACKGROUND & AIMS: There is an increased risk of colorectal carcinoma (CRC) in patients with longstanding, extensive colonic inflammatory bowel disease (IBD). Primary sclerosing cholangitis, family history of CRC, mucosal dysplasia and DNA-aneuploidy are other risk factors. Recently, results from animal studies have shown that the bile acid ursodeoxycholic acid (UDCA) has a favourable impact on experimentally-induced CRC/neoplasia in rats. The aim of this proof of the concept study was to explore the possible preventive/reverting effects of UDCA in patients with colorectal IBD with existing findings of low grade dysplasia and/or DNA-aneuploidy. PATIENTS AND METHODS: Nineteen patients (13 UC, 6 CD, median age 43 years) with long-standing, extensive IBD (median duration 21 years), with previous findings of low-grade dysplasia and/or DNA-aneuploidy, were randomized to receive either UDCA (500 mg b.i.d) (n=10) or placebo (n=9) in a controlled, double-blind, two-year study. Colonoscopy with multiple biopsies for histopathology and for DNA-flow cytometry was performed at the start and at six-month intervals during the study period. The primary outcome was the need for colectomy due to progression of dysplasia. Changes in dysplasia and DNA-aneuploidy scores were also assessed. RESULTS: There were no significant differences in the overall composed score between the two groups, either at study start or during the study period. In the placebo group one patient had a progression of dysplasia into high-grade and one patient developed DALM with low-grade dysplasia; both had a colectomy. In contrast, no UDCA-treated patient had progression of dysplasia. CONCLUSION: UDCA may prevent further progression of manifest low-grade dysplasia in colorectal IBD. Prolonged treatment or an increased dose may be needed to fully exploit the chemopreventive properties of this compound.

Adult↗
PubMed2001

Ethnic differences in allelic associations of the interleukin-1 gene cluster in South African patients with inflammatory bowel disease (IBD) and in control individuals.

The allelic frequencies of TaqI, PstI, and variable number of tandem repeat (VNTR) polymorphisms of the IL-1beta, IL-1 receptor (IL-1Re), and IL-1 receptor antagonist (IL-1Ra) respectively, were investigated in black and white patients with inflammatory bowel diseases (IBD) and compared with control individuals. Plasma concentrations of IL-1beta and IL-1Ra were also determined in these individuals. The IL-1beta TaqI(-) allele was significantly more frequent in 50 white IBD patients (60%) compared with 47 white controls (17%), and 20 black patients (20%) (P=0.00001 and P=0.0001, respectively). The IL-1Re PstI(-) allele was significantly more frequent in 20 black patients (75%) compared with 50 white patients (44%) (P=0.0001). The frequency of the IL-1Ra 240-bp allele was lower in black (12%) compared with white controls (25%), (P=0.0151), and the 410-bp allele was more frequent in black (87%) compared with white (73%) controls (P=0.0096). Linkage disequilibrium was found in black individuals homozygous for the 410-bp allele of IL-1Ra, and the PstI(-) allele of IL-1Re (84%) (P=0.0032). There was a significantly increased level of IL-1Ra in black patients compared with white patients and black controls (P=0.0006 and P=0.0008, respectively). The population differences in allelic frequencies of the IL-1 gene cluster and IL-1Ra concentrations suggest that genetic and environmental factors play an important role in susceptibility to IBD.

Adolescent↗
PubMed2000

Laparoscopic-assisted vs open colectomy for severe acute colitis in patients with inflammatory bowel disease (IBD): a retrospective study in 42 patients.

BACKGROUND: Inflammatory bowel disease (IBD) can be complicated by severe acute colitis. Emergency colectomy is mandatory if patients do not respond to intensive medical therapy. A minimally invasive approach such as laparoscopic-assisted colectomy might be beneficial in these patients. Therefore, we set out to assess the feasibility and the safety of emergency laparoscopic-assisted colectomy in IBD patients with severe acute colitis. METHODS: A total of 42 consecutive patients underwent an emergency colectomy with end-ileostomy. Ten patients had laparoscopic-assisted colectomy, and 32 had open colectomy. Pre- and perioperative parameters, morbidity, and mortality were analyzed. RESULTS: The two groups were comparable for patient characteristics. There were no conversions in the laparoscopic group. The operation time was longer in the laparoscopic group than in the open group (271 vs 150 min; p < 0.001), but the hospital stay was shorter (14.6 vs 18.0 days; p = 0.05). Complications were similar for the two groups. CONCLUSION: Laparoscopic-assisted colectomy in IBD patients with severe acute colitis is feasible and as safe as open colectomy.

Acute Disease↗
PubMed1992

Familial aggregation of inflammatory bowel disease in northern Italy: a multicenter study. The Gruppo di Studio per le Malattie Infiammatorie Intestinali (IBD Study Group).

To assess the familial aggregation of inflammatory bowel disease (IBD) in Italy, the family pedigrees of 411 patients with ulcerative colitis (UC) and 241 patients with Crohn's disease (CD) seen at 14 participating hospitals were studied. Sufficient information was obtained on 97% of 3752 first-degree relatives, 80% of 8869 second-degree relatives, and 74% of 5791 cousins. Thirty-six propositi (5.52%) had a total of 44 affected relatives (16 CD, 28 UC). The prevalence of IBD was higher in first- than in second-degree relatives and cousins (791, 112, and 163 in 100,000, respectively). A strong intrafamilial disease concordance was observed, with 26 cases of UC and 6 of CD among relatives of UC patients and 10 cases of CD and 2 of UC among relatives of CD patients. The prevalence of UC among first-degree relatives of UC patients and that of CD among first-degree relatives of CD patients was 680 and 531 in 100,000, respectively. In conclusion, there is a high degree of familial aggregation for IBD in Italy, with a strong intrafamilial disease concordance.

Adolescent↗
PubMed2005

Aetiology of inflammatory bowel disease (IBD): role of intestinal microbiota and gut-associated lymphoid tissue immune response.

The aetiology of inflammatory bowel disease (IBD) probably involves a combination of genetic predisposition and environmental factors that may be channelled through an abnormality in gut-barrier function, with a loss of antigen tolerance. Some genetic markers that predispose to inflammatory disease have been identified (alleles DR2, DRB1*0103, DRB1*12 and mutations in the NOD2/CARD15 gene on chromosome 16). Alterations in the pattern of cytokine production by T cell subclasses leading to loss of tolerance to oral antigens have been documented. Moreover, a number of environmental factors (cigarette smoking, use of non-steroid anti-inflammatory drugs, psychological stress and the presence of the caecal appendix) have been postulated as a trigger of IBD. It has also been suggested that the gut microbiota plays a major role in the development and persistence of IBD, and numerous modifications of intestinal microbiota composition have been identified. As a result, manipulation of the microbiota with antibiotics is a current therapeutic strategy; more recently, however, a number of studies have reported promising results when using probiotic organisms to manipulate gut microbiota composition in order to restore tolerance to microbial antigens of the host's own microbiota.

Animals↗
PubMed2005

A multicenter assessment of liver toxicity by MRI and biopsy in IBD patients on 6-thioguanine.

BACKGROUND/AIMS: Although 6-thioguanine (6-TG) has been suggested as an effective treatment option for patients with inflammatory bowel disease (IBD), the recent description of its hepatotoxicity has led to the recommendation not to consider this drug. We initiated a multicenter safety study in IBD-patients treated with 6-TG to investigate hepatic changes by liver biopsy and magnetic resonance imaging (MRI). METHODS: Forty-five patients from three European centers treated with 6-TG (40-80 mg/d) at least for 8 weeks were enrolled. In all patients liver biopsy and MRI were performed. Slides and MR images were independently read by two pathologists and radiologists, respectively, and interpreted according to predefined criteria by consent. RESULTS: In 8 patients nodular regenerative hyperplasia (NRH) was diagnosed by liver biopsy, in 8 additional patients NRH could not be excluded due to equivocal pathological findings. MRI demonstrated a sensitivity of 77% and a specificity of 72% in the detection of pathohistological findings consistent with and/or possibly related to NRH. CONCLUSIONS: Our study suggests that 6-TG therapy in IBD patients is associated with NRH of the liver. Based on a special MRI protocol, non-invasive diagnosis of NRH with promising sensitivity and specificity was demonstrated.

Adult↗
PubMed1997

Refractory IBD: medical management.

Refractory inflammatory bowel disease (IBD) can be defined as persistent acute symptomatic disease despite anti-inflammatory therapy or as chronically active disease requiring continuous treatment for relief of symptoms. Treatment options include azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate (MTX), cyclosporine (CYA), and experimental therapies that are cytokines or cytokine antagonists. AZA and 6-MP have identical actions in IBD. 6-MP is effective in about 75% of patients with inflammatory Crohn's disease. The mean time until the onset of action is 3.1 months. AZA is effective in ulcerative colitis as a steroid-sparing agent. Side-effects occur in 10-15% of patients on AZA or 6-MP for IBD. MTX induces symptomatic remission in about 40% of patients with Crohn's disease. The potential for hepatic fibrosis from MTX is a concern. CYA appears effective in the acute management of severe ulcerative colitis. CYA has not proven useful in the long-term management of Crohn's disease. Potentially serious side-effects include hypertension and renal insufficiency. The cytokine antagonist, anti-tumor-necrosis-factor-alpha antibody, and the anti-inflammatory cytokine, interleukin 10, appear promising for the treatment of Crohn's disease.

Azathioprine↗
PubMed2002

Inflammation and colorectal cancer: IBD-associated and sporadic cancer compared.

Ulcerative colitis and colonic Crohn's disease (together known as inflammatory bowel disease or IBD) are both associated with increased risk for colorectal cancer. Although it is customary to emphasize differences in the biology of IBD-associated and sporadic colon cancer, we believe these are far outweighed by the similarities. These similarities suggest that they might have similar pathogenic mechanisms. Because the normal colon is arguably in a continual state of low-grade inflammation in response to its microbial flora, it is reasonable to speculate that both IBD-associated and sporadic colon cancer might be the consequence of bacteria-induced inflammation.

Colorectal Neoplasms↗
PubMed2001

Pathology of inflammatory bowel diseases (IBD): variability with time and treatment.

The diagnosis of chronic idiopathic IBD and the differential diagnosis between Crohn's disease and ulcerative colitis can be made in most cases on cumulative clinical, radiological, endoscopical, biochemical and pathological evidence. Diagnostic difficulties can however, occur in fulminant colitis, in early onset disease and in long-standing disease. The microscopic evaluation of disease activity is based on the presence of active inflammation. Effective medical treatment has however, an influence upon the morphology and the evolution of the lesions and hence can affect the diagnostic features and the microscopic features used for the assessment of disease activity. A literature review was performed on clinical drug trials in IBD and the effect of the drugs upon the microscopic features. Several studies have shown that the diagnostic microscopic features and the features characteristic for disease activity vary with time and treatment. For an adequate analysis of biopsy samples of patients with IBD the pathologist should be aware of the duration of the symptoms and the type of treatment given to the patient.

Journal Article↗
PubMed2006

[The peroxisome-proliferator-activated gamma receptor and chronic inflammatory bowel disease (PPARgamma and IBD)].

PPARgamma has been recently described as being a gene of susceptibility for Intestinal Bowel Diseases (IBD) as NOD2/CARD15 gene. IBD are pathologies due to an abnormal immune response, in genetically predisposed patients, to the bacteria of the intestinal flora. PPARgamma, known for its significant role in adipogenesis, is strongly expressed by the epithelial cells of the colon mucosa. PPARgamma is implicated in the regulation of inflammation. Indeed, agonists of this nuclear receptor decrease strongly the intensity of inflammation during experimental colitis induced by chemical agents. A deficit of PPARgamma in patients with ulcerative colitis has been highlighted, that could in part explain the acute inflammation. In addition, bacteria, including those of the commensal flora, are able to regulate PPARgamma. Toll Like Receptor-4 (TLR-4), responsible for the recognition of bacterial motif as lipopolysaccharide (LPS), is implicated in PPARgamma regulation and its anti-inflammatory properties. All these arguments make of PPARgamma a very interesting therapeutic target for the treatment of IBD.

Animals↗
PubMedDate not supplied

[Quality of life assessment in Inflammatory Bowel Disease (IBD): German version of the Inflammatory Bowel Disease Questionnaire (IBDQ-D; disease-specific instrument for quality of life assessment) -- first application and comparison with international investigations].

BACKGROUND: Health-related quality of life (HRQOL) is an important outcome-parameter in health research and care. The aim of the working group Quality of Life in the Competence Network Inflammatory Bowel Disease (IBD; in the original German: "Kompetenznetz chronisch entzündliche Darmerkrankungen") is to generate instruments for assessment of HRQOL and its implementation as standards in clinical trials, health care and research in IBD. METHODS: The Inflammatory Bowel Disease Questionnaire (IBDQ) is an international validated disease specific instrument for HRQOL-assessment. A German version of the IBDQ was elaborated and tested in 415 outpatients with Crohn's disease (CD, n = 306) and ulcerative colitis (UC, n = 109). The aim of the study was to compare the results of HRQOL-assessment (IBDQ-D) with international investigations, to correlate HRQOL results with disease activity and to preform a pretest of psychometric properties. RESULTS: International data suggest that the IBDQ-D is a suitable instrument for HRQOL-assessment in CD and UC. For both disease a statistically significant negative correlation with disease activity was found. Tested psychometric properties do not suggest that a revision of the IBDQ-D is required. The IBDQ-D offers the HRQOL-assessment as an primary or secondary outcome in clinical trials in IBD in Germany.

Adult↗
PubMed2006

[Validation of the German version of the Inflammatory Bowel Disease Questionnaire (Competence Network IBD, IBDQ-D)].

The Inflammatory Bowel Disease Questionnaire (IBDQ) is the standard disease-specific instrument for assessment of health-related quality of life (HRQOL) in patients with inflammatory bowel diseases (IBD). A German translation has not been validated. 415 outpatient IBD-patients (Crohn's Disease n = 306, Ulcerative Colitis n = 109) completed the German version of the IBDQ (Competence network IBD, IBDQ-D), the Hospital Anxiety and Depression Scale German Version (HADS-D) and the Questions on Life Satisfaction FLZ. Face validity was assessed by a physicians' and patients' panel. Disease activity was measured by the German Inflammatory Bowel Disease Activity Index (GIBDI). With 97.3 % completed items the acceptance was high. The Cronbach's alpha for the subscales ranged from 0.88 to 0.89. The correlation coefficients with comparable subscales of other instruments ranged between 0.09 and 0.70. Patients in remission and different disease activities differed significantly (p < 0.001) in all IBDQ-D-subscales.

Adult↗
PubMed2001

In vitro effects of naloxone on T-lymphocyte-dependent antibacterial activity in hepatitis C virus (HCV) infected patients and in inflammatory bowel disease (IBD) patients.

Naloxone acts as an opioid antagonist, displacing opioid drugs from cellular receptors. Among opioid substances, beta-endorphins are able to bind to several cell receptors, even including those expressed by immune cells. In this respect, evidence has been provided that in the course of viral infections, as well as in patients with ulcerative colitis high levels of beta-endorphins are detectable. Here, peripheral blood lymphocytes (PBL) from 21 HCV infected patients and 14 patients with IBD, respectively, were incubated with Naloxone and Naloxone + Ca2+ in order to evaluate a putative modulation of PBL-mediated antibacterial activity. In fact, previous studies have demonstrated a reduction of this T-cell activity in HCV and IBD patients. In general terms, the above treatment led to a recovery of the depressed antibacterial activity. In some cases, increase in T lymphocyte function was obtained with Naloxone alone, while in other cases the combination Naloxone + Ca2+ gave rise to a restorative effect. Of note, in some instances, lymphocytes were unresponsive to pharmacological modulation. The overall results suggest that beta-endorphins may down modulate T-cell antibacterial response in HCV and in IBD patients by saturating peripheral receptors on immune cells. Therefore, it is likely that Naloxone and/or Naloxone + Ca2+ may displace opioid drugs, thus antagonizing their effects.

Adolescent↗
PubMed2000

Evaluation of the effectiveness of a specialist nurse in the management of inflammatory bowel disease (IBD).

OBJECTIVE: To determine the effect of a specialist nurse on the management outcome of patients with inflammatory bowel disease (IBD). DESIGN: Audit of the management of a cohort of patients in the year prior to the employment of the specialist nurse and the year immediately after. SUBJECTS: 339 patients, both male and female, with either Crohn's disease or ulcerative colitis, resident in the Cambridge health district. SETTING: Addenbrooke's Hospital NHS Trust Outpatient Centre. MAIN OUTCOME MEASURE: Health status was measured by blood tests (C-reactive protein, albumin and haemoglobin) throughout the year, symptom indices, number of clinic attendances, admissions to hospital and length of stay. Quality of life was measured via a postal questionnaire. RESULTS: Hospital visits were reduced from 1377 to 853 (38% reduction) and in-patient length of stay measured in bed-days from 516 to 417 (19% reduction). The number of patients in remission increased from 63 to 69%. Patient satisfaction improved in key areas, in particular, access to information on IBD and advice on avoidance of illness and maintaining health. Of a total of 251 calls to the telephone helpline, only 19 patients were referred for a medical opinion and five patients required hospital admission. CONCLUSION: The IBD nurse specialist is a valuable and cost-effective member of the gastroenterology team.

Adolescent↗
PubMed2000

Anemia in IBD: the overlooked villain.

During the past decade relevant progress has been made in the understanding and treatment of IBD-associated anemia. Effective replacement of iron deficits has become safe by using novel intravenous iron preparations such as iron sucrose. The ability of erythropoietin to interfere with key mechanisms of myelosuppression in anemia of chronic diseases also benefits patients with IBD-associated anemia. Concerns about cost effectiveness have been raised and weighed against the potential improvement in quality of life. Gastroenterologists who are caring for IBD patients should be concerned with low hemoglobin levels, since the quality of life in these patients can be as low as in anemic patients with advanced cancer. Also provided is a structured approach to cost-effective therapy.

Anemia↗
PubMed2001

Inflammation location, but not type, determines the increase in TGF-beta1 and IGF-1 expression and collagen deposition in IBD intestine.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is frequently complicated by extracellular matrix (ECM) changes that may result in fibrosis. Transforming growth factor (TGF)-beta1 and insulin-like growth factor (IGF)-1 mediate numerous ECM changes. Our aim was to determine whether TGF-beta1 and IGF-1 are involved in intestinal ECM collagen regulation and what impact the inflammatory infiltrate has on their expression. METHODS: TGF-beta1 and IGF-1 mRNA and protein were assessed in fibrosed Crohn's disease (CD), inflamed CD, inflamed ulcerative colitis (UC), and control intestine using in situ hybridization and immunohistochemistry. Collagen types I and III were quantified by electron immunohistochemistry. RESULTS: In CD, increased TGF-beta1 and IGF-1 mRNA expression was transmural. In UC, the increase was confined to the lamina propria and submucosa. In both, distribution of TGF-beta1 and IGF-1 protein matched mRNA expression and coincided with the distribution of the inflammatory infiltrate. An increase in the collagen type III:I ratio in both CD and UC also coincided with the inflammatory infiltrate. CONCLUSIONS: These findings suggest that TGF-beta1 and IGF-1 are involved in intestinal ECM remodeling in IBD, and their enhanced expression depends on the presence and location of inflammatory infiltrates rather than the type of IBD.

Collagen↗